Immune response after two doses of the novel split virion, adjuvanted pandemic H1N1 influenza A vaccine in HIV-1-infected patients.
To determine the rate of seroconversion after 2 doses of a novel split virion, inactivated, adjuvanted pandemic H1N1 influenza vaccine (A/California/7/2009) in human immunodeficiency virus type 1 (HIV-1)-infected patients (ClinicalTrials.gov NCT01017172). Diagnostic study of adult HIV-1-infected patients scheduled for H1N1 influenza A vaccination. Blood samples where taken before and 21 days after the first dose and 21 days after the second dose of the vaccine. Antibody (AB) titers were determined by hemagglutination inhibition assay. Seroconversion was defined by either an AB titer ≤ 1:10 before and ≥ 1:40 after or ≥ 1:10 before and a ≥ 4-fold increase in AB titer 21 days after vaccination. One hundred thirty-five patients received 2 doses of the H1N1 vaccine and were analyzed. The rate of seroconversion was 68.2% (95% confidence interval, 59.6-75.9) after the first dose and 91.9% (95% confidence interval, 85.9-95.9) after the second dose. Patients who did not seroconvert had a lower mean nadir CD4 cell count (± standard deviation; 81 ± 99 vs 190 ± 148 cells/μL; P = .006), had a longer duration of HIV infection (± standard deviation; 13.1 ± 5.9 vs 8.8 ± 6.8 years; P = .04), and were more likely to have an AB titer ≥ 1:40 before vaccination (4% vs 55%; P < .001) when compared with patients with seroconversion. No other differences were found between the 2 groups, including AIDS status, highly active antiretroviral therapy status, HIV RNA - polymerase chain reaction load <50 copies/mL, CD4 cell count, sex, body mass index, and chronic hepatitis. Among HIV-infected patients, the rate of seroconversion after the first dose of an adjuvanted H1N1 influenza A vaccine was 68% and increased to 92% after a second doses.


Nanomechanical properties and molecular structures of in vitro mineralized tissues on anodically-oxidized titanium surfaces.
The biomechanical stability of mineralized tissues at the interface between implant surface and bone tissue is of critical importance. Anodically oxidized titanium prepared in a chloride solution results in enhanced mineralization of adherent osteoblasts and has antimicrobial activity against oral microorganisms. We evaluated the nanomechanical properties and molecular structures of the in vitro mineralized tissues developing around anodically oxidized titanium surfaces with and without preparation in chloride solution. Anodically oxidized titanium surfaces showed superior osteogenic gene expressions than those of thermally oxidized and bare titanium surfaces. Preparation of anodically oxidized titanium in chloride enhanced the production of mineralized tissue around it. However, the mineralized tissue around anodically oxidized titanium prepared without chloride had increased mineral:matrix and cross-linking ratios, resulting in higher hardness and lower elasticity. In this study anodically oxidized titanium was used to enhance the biomechanical stability of mineralized tissues at the implant surface -- bone tissue interface. The mineralized tissue around anodically oxidized titanium prepared without chloride had increased mineral:matrix and cross-linking ratios, resulting in higher hardness and lower elasticity.


Distribution of hepatitis C virus genotypes among injecting drug users in contact with treatment centers in Belgium, 2004-2005.
The aim of this study was to determine the current prevalence of HCV genotypes in injecting drug users recruited at treatment centers all over Belgium, and to analyze if the distribution of genotypes was correlated with demographic characteristics, at-risk behaviors, and co-infection with other viruses. Therefore 147 anti-HCV-positive serum samples were selected for subsequent HCV RNA detection and genotyping. HCV RNA could be detected in 98 (67%) of the 147 serum samples. Genotype 1 (38%) and 3 (49%) were the most common genotypes followed by genotype 4 (9%) and genotype 2 (2%). One mixed infection (1%) was detected. The subtype could be determined in 80 cases: genotype 3a was the most prevalent (49%), followed by genotype 1a (16%) and genotype 1b (15%). No significant difference was found between the distribution of genotypes and the location of treatment centers, at-risk behaviors and co-infection with other viruses. Nevertheless, a slight variation over time could be identified (P = 0.06): one in two genotype 3 drug users started with their injecting drug use in the last 10 years (33% in the period 1995-1999 and 21% in the period > or =2000) compared to only one in four genotype 1 drug users (20% in the period 1995-1999 and 9% in the period > or =2000).


The potential role of excessive cortisol induced by HPA hyperfunction in the pathogenesis of depression.
Prolonged hypothalamic-pituitary-adrenocortical (HPA) axis overactivity occurs at all levels of this axis during stress in normals and some depressed patients. This can induce enlargement of the pituitary and adrenals. Various reports showed that cortisol can affect mood and behavior, and disrupt memory and recall. The integrity of the hippocampus is essential for memory function and, via the high density of its cortisol receptors, cortisol induced inhibitory feedback to the HPA axis. Animal data suggest that over time aging and stress can permanently downregulate hippocampal cell receptors, produce chronic hippocampal inflammation (astroglial), and kill cells. Cushing's syndrome patients (high cortisol) show diminished hippocampal size and verbal recall inversely related to cortisol levels. All the above is consistent with the 'cascade hypothesis' of cortisol induced hippocampal damage with resultant diminished inhibition to HPA hyperactivity in a circular manner. High cortisol is associated with altered neurotransmitter function, e.g., diminished brain serotonin synthesis, low CSF 5HIAA, and increased noradrenergic activity.


Laparoscopy as the investigation and treatment of choice for urinary incontinence caused by small 'invisible' dysplastic kidneys with infrasphincteric ureteric ectopia.
To report our experience of using laparoscopy for the accurate location and simultaneous removal of small dysplastic kidneys with ectopic ureteric insertion causing urinary incontinence and that were not detected by conventional imaging modalities. Seven girls (mean age 7.9 years, range 3.5-13) presented with urinary leakage occurring between normal voids. Imaging studies including ultrasonography, renal scintigraphy, intravenous urography, computed tomography and/or magnetic resonance imaging in six of the seven patients revealed a single normal functioning kidney, but failed to detect the contralateral nonfunctioning dysplastic kidney. All patients were examined under anaesthesia, followed by transperitoneal laparoscopy for the simultaneous localization and removal of the dysplastic kidneys under the same setting. Laparoscopy in all seven patients revealed a small dysplastic kidney that could always be easily located by first finding the draining ureter over the iliac vessels and then following it upwards. Four dysplastic kidneys were found in the renal fossa (two left, two right). One kidney was found at the left iliac fossa just above the pelvic brim, one at the left lumbar region, and the other at the right iliac fossa. Laparoscopic nephroureterectomy was successful in all seven girls and the patients were discharged 48 h after surgery. The follow-up (mean 2.7 years, range 3 months-5.4 years) showed excellent cosmetic results and all the patients have remained completely dry. In patients with a classical picture of urinary incontinence caused by infrasphincteric ureteric ectopia associated with a small nonfunctioning kidney, video-laparoscopy, with its magnifying effect, can reliably confirm the diagnosis, locate the dysplastic kidney and allow its removal in the same setting. We propose that laparoscopy should be considered the investigation and treatment of choice in such patients, and should be undertaken without delay even if the dysplastic kidney or the ectopic ureteric orifice cannot be identified with all other conventional means.


The C-terminal tail of human neuronal calcium sensor 1 regulates the conformational stability of the Ca²⁺₋ activated state.
Neuronal calcium sensor 1 (NCS-1) and orthologs are expressed in all organisms from yeast to humans. In the latter, NCS-1 plays an important role in neurotransmitter release and interacts with a plethora of binding partners mostly through a large solvent-exposed hydrophobic crevice. The structural basis behind the multispecific binding profile is not understood. To begin to address this, we applied NMR spectroscopy to determine the solution structure of calcium-bound human NCS-1. The structure in solution demonstrates interdomain flexibility and, in the absence of a binding partner, the C-terminal tail residues occupy the hydrophobic crevice as a ligand mimic. A variant with a C-terminal tail deletion shows lack of a defined structure but maintained cooperative unfolding and dramatically reduced global stability. The results suggest that the C-terminal tail is important for regulating the conformational stability of the Ca(2+)-activated state. Furthermore, a single amino acid mutation that was recently diagnosed in a patient with autistic spectrum disorder was seen to affect the C-terminal tail and binding crevice in NCS-1.


2003 World Health Organization (WHO)/International Society of Hypertension (ISH) statement on management of hypertension.
Hypertension is estimated to cause 4.5% of current global disease burden and is as prevalent in many developing countries, as in the developed world. Blood pressure-induced cardiovascular risk rises continuously across the whole blood pressure range. Countries vary widely in capacity for management of hypertension, but worldwide the majority of diagnosed hypertensives are inadequately controlled. This statement addresses the ascertainment of overall cardiovascular risk to establish thresholds for initiation and goals of treatment, appropriate treatment strategies for non-drug and drug therapies, and cost-effectiveness of treatment. Since publication of the WHO/ISH Guidelines for the Management of Hypertension in 1999, more evidence has become available to support a systolic blood pressure threshold of 140 mmHg for even 'low-risk' patients. In high-risk patients there is evidence for lower thresholds. Lifestyle modification is recommended for all individuals. There is evidence that specific agents have benefits for patients with particular compelling indications, and that monotherapy is inadequate for the majority of patients. For patients without a compelling indication for a particular drug class, on the basis of comparative trial data, availability, and cost, a low dose of diuretic should be considered for initiation of therapy. In most places a thiazide diuretic is the cheapest option and thus most cost effective, but for compelling indications where other classes provide additional benefits, even if more expensive, they may be more cost effective. In high-risk patients who attain large benefits from treatment, expensive drugs may be cost effective, but in low-risk patients treatment may not be cost-effective unless the drugs are cheap.


Actual frequency of imaging during follow-up of testicular cancer in Israel-a comparison with the guidelines.
Computed tomography (CT) examinations are frequent in follow-up care of testicular cancer (TC) but may increase the risk for other cancers. We wanted to assess the actual number of CT and X-ray examinations within the first 5 years after a diagnosis of TC in Israel during 2003-2007. The database of Maccabi Healthcare Services, Israel, was searched for TC patients diagnosed in 2003 to 2007 by direct linkage with the Israel National Cancer Registry. Data on diagnostic imaging examinations (CT of chest, abdomen, or pelvis, unspecified sites; X-ray of chest) were extracted during a 5-year follow-up for 226 incident patients. The actual number of CT and X-ray examinations was compared to the National Comprehensive Cancer Network (NCCN) guideline. We tabulated the median with 10th and 90th percentiles (P10, P90) for the number of CTs and X-rays considering histology, stage, and adjuvant strategy. The number of abdomen or pelvis CTs for TC patients receiving chemo- or radiotherapy was in accordance with the NCCN guideline. The median of abdomen or pelvis CTs for surveillance patients was 8.5 (P10, P90: 3; 13) for nonseminoma and 5.0 (P10, P90: 5; 13) for seminoma patients compared to 14 to 17 CTs recommended. The number of chest X-rays was lower than recommended in the guideline for all adjuvant strategies. The NCCN guidelines regarding CTs were met for TC patients treated with chemo- or radiotherapy but fell below recommendations for surveillance. Guidelines from 2011 and 2012 were updated in favor of fewer CTs during surveillance. • The number of CTs followed the NCCN guidelines in patients treated with chemo- or radiotherapy. • Surveillance patients received fewer CTs and X-rays than recommended in the NCCN guidelines from 2005. • The number of applied CT examinations corresponded to a radiation dose that did not substantially raise the lifetime risk for cancer.


A Comparison of Secondary Polycythemia in Hypogonadal Men Treated with Clomiphene Citrate versus Testosterone Replacement: A Multi-Institutional Study.
We evaluated the relative prevalence of secondary polycythemia in hypogonadal men treated with clomiphene citrate or testosterone replacement therapy. In this retrospective, multi-institutional study, we included 188 men who received clomiphene citrate and 175 who received testosterone replacement therapy with symptomatic hypogonadism. The overall prevalence and ORs of secondary polycythemia for clomiphene citrate treatment vs testosterone replacement were primarily measured, as were baseline characteristics. Subset analysis included polycythemia rates for different types of testosterone replacement therapy. Overall, men on testosterone replacement therapy were older than clomiphene citrate treated men (age 51.5 vs 38 years). Men on testosterone replacement had longer treatment duration than clomiphene citrate treated men (19.6 vs 9.2 months). For testosterone replacement therapy and clomiphene citrate the mean change in hematocrit was 3.0% and 0.6%, and the mean change in serum testosterone was 333.1 and 367.6 ng/dl, respectively. The prevalence of polycythemia in men on testosterone replacement was 11.2% vs 1.7% in men on clomiphene citrate (p = 0.0003). This significance remained on logistic regression after correcting for age, site, smoking history and pretreatment hematocrit. The prevalence of polycythemia in men treated with clomiphene citrate was markedly lower than that in men on testosterone replacement therapy. The improvement in absolute serum testosterone levels was similar to that in men on testosterone replacement. There is no significant risk of polycythemia in men treated with clomiphene citrate for hypogonadism.


Synchronized spike waves in immature dentate gyrus networks.
At early developmental stages, immature neuronal networks of the neocortex and hippocampus spontaneously exhibit synchronously oscillating activities, which are believed to play roles in normal circuit maturation. The tissue development of the dentate gyrus (DG) in the hippocampal formation is exceptionally late compared with other brain regions and persists until postnatal periods. Using patch-clamp recording and functional multineuron calcium imaging, we found that the DG networks of postnatal day (P)3-7 mice spontaneously generated traveling waves of action potentials, which were initiated at the upper blade of the granule cell layer and propagated to the lower blade. The propagation was dependent on glutamatergic and electrical synapses, but not on GABAergic receptor activity. Remarkably, the DG waves were almost completely abolished in offspring born to female rats exposed to restraint stress during pregnancy. In the prenatally stressed offspring, DG granule cell dendrites developed normally until P3 and showed atrophy by P9. Thus, the DG waves may be required for the maturation of DG granule cells.


Delineating immune-mediated mechanisms underlying hair follicle destruction in the mouse mutant defolliculated.
Defolliculated (Gsdma3(Dfl)/+) mice have a hair loss phenotype that involves an aberrant hair cycle, altered sebaceous gland differentiation with reduced sebum production, chronic inflammation, and ultimately the loss of the hair follicle. Hair loss in these mice is similar to that seen in primary cicatricial, or scarring alopecias in which immune targeting of hair follicle stem cells has been proposed as a key factor resulting in permanent hair follicle destruction. In this study we examine the mechanism of hair loss in GsdmA3(Dfl)/+ mice. Aberrant expression patterns of stem cell markers during the hair cycle, in addition to aberrant behavior of the melanocytes leading to ectopic pigmentation of the hair follicle and epidermis, indicated the stem cell niche was not maintained. An autoimmune mechanism was excluded by crossing the mice with rag1-/- mice. However, large numbers of macrophages and increased expression of ICAM-1 were still present and may be involved either directly or indirectly in the hair loss. Reverse transcriptase-PCR (RT-PCR) and immunohistochemistry of sebaceous gland differentiation markers revealed reduced peroxisome proliferator-activated receptor-γ (PPARγ), a potential cause of reduced sebum production, as well as the potential involvement of the innate immune system in the hair loss. As reduced PPARγ expression has recently been implicated as a cause for lichen planopilaris, these mice may be useful for testing therapies.


Therapeutic pancreatic endoscopy.
Over the past decade, endoscopic retrograde cholangiopancreatography (ERCP) has developed from being a diagnostic tool to become one that is primarily used to provide therapy. This development occurred first for biliary disorders and more recently for primary diseases of the pancreas. Not only can new-generation computed tomography (CT), magnetic resonance imaging, and magnetic resonance cholangiopancreatography procedures suggest a diagnosis in the majority of individuals with pancreatic diseases today; in addition, ERCP-related complications can be minimized or avoided altogether in conjunction with positron-emission tomography or directed cytology or biopsy, either using ultrasound or CT guidance, or with tissue obtained during endoscopic ultrasonography. It is against this background that papers on therapeutic pancreatic endoscopy published during approximately the last year are reviewed here. Despite these developments, however, the following three issues concerning current advances in pancreatic endotherapy should be emphasized: firstly, most of the techniques reviewed here affect only a small number of patients; secondly, most of the techniques have been reported only by expert centers; and thirdly, most of the studies concerned have lacked control groups, and there is still a paucity of studies investigating endoscopic techniques on a randomized basis in comparison with surgery or medical therapy for the treatment of most benign and malignant pancreatic disorders.


Cost-effectiveness of coronary angioplasty versus medical treatment: the impact of cost-shifting.
Coronary angioplasty (PTCA) offers improved symptom control over medical treatment in patients with stable angina and single-vessel disease. However, it is uncertain if PTCA is more cost-effective. Cost-shifting could also influence the provision of PTCA. Data from the only randomised trial comparing PTCA to medical therapy (ACME study) were used with costs from an Australian teaching hospital to estimate the costs and freedom from angina in 100 patients over three years. The incremental cost-effectiveness of PTCA, and the potential for cost-shifting were also examined. Although the total cost of treating 100 patients over three years with PTCA ($678,978) was higher than a medical strategy ($631,078), PTCA was more cost-effective ($10,930 versus $12,682 per patient free of angina). The incremental cost-effectiveness of PTCA ($3875 per extra patient free of angina) was also substantially less than the cost of the medical strategy. These should be considered crude estimates as they were based on limited data on resource use. The hospital could reduce costs by pursuing a medical strategy, but 54% of the savings would result from shifting the cost of treating patients to the Federal Government and patients. By performing PTCA on privately insured rather than Medicare patients, the hospital could shift $29,876 per 100 patients to the Federal government and private insurance funds. From society's perspective, PTCA may be more cost-effective than a medical strategy. However, the financial interests of the hospital are best served by limiting PTCA or restricting PTCA to privately insured patients. Cost-shifting may have a major impact on the provision of PTCA. The costs of providing medical services need to be weighed against the cost of not providing them.


The agonistic and antagonistic actions of estriol.
Estriol is a short acting estrogen, and as such, displays both agonistic and antagonistic properties, when it is injected in saline solution. These are predictable attributes of any short acting agonist if one considers the basic pharmacology of receptor ligand binding interactions. That is, short acting hormones or drugs occupy receptor sites for protracted time periods and, although they stimulate responses, these are of short duration. However, when estriol is administered in continuous fashion the estrogen receptor is occupied for long periods of time and full estrogenic responses are observed, and there is no antagonism of estradiol action. The purpose of this paper is to review the work that leads to the above conclusion and to discuss our more recent work on the relationship between estrogen receptor binding and the stimulation of type II estrogen binding sites.


Assessment of the cross-reactivity and binding sites characterisation of a propazine-imprinted polymer using the Langmuir-Freundlich isotherm.
In this paper, the Langmuir-Freundlich isotherm is used to model the interaction of several triazines (desethylatrazine, desisopropylatrazine, simazine, atrazine, propazine and prometryn) with a propazine-imprinted polymer and to explain the observed cross-reactivity. Different rebinding experiments (each herbicide alone or all together in a mixture) were carried out and the experimental binding isotherms were fitted to the Langmuir-Freundlich isotherm. The fitting coefficients obtained (total number of binding sites, mean binding affinity and heterogeneity index) allowed the description of the kind of binding sites present in the imprinted polymer under study. It was concluded that the recognition mechanism was mainly governed by the molecular size although slight differences in the molecular structure may also play an important role. The obtained results suggest that the use of this new methodology can open new pathways for understanding how molecular recognition in imprinted polymers takes place.


Reproductive health knowledge, attitudes and practices of Iranian college students.
To study reproductive health knowledge, attitudes and practices of youth in the Islamic Republic of Iran, 1111 university students completed a questionnaire with 43 closed questions. The overall mean knowledge score was 54%. Knowledge of males and females, and of married and single students, was similar. Of 664 students answering questions about reproductive health behaviour, 54 (8%) reported having sexual intercourse before marriage; 16% of males and 0.6% of females; 48% of them had used condoms. The majority of students believed that the risk of AIDS and other sexually transmitted infections was moderate but that youth had a low ability to practise healthy behaviour. The majority believed in the benefits of reproductive health knowledge for youth but felt that services were inadequate.


Determinants of non-participation in a mass screening program for colorectal cancer in Finland.
For an effective colorectal cancer (CRC) screening program, high participation rate is essential. However, non-participation in CRC screening program has increased in Finland. The study was based on a population-based nationwide cohort of persons invited for CRC screening in 2004-2011. Information on the first round of the CRC screening participation and related background factors was obtained from the Finnish Cancer Registry, and information about health behavior factors from the Health Behavior Survey (HBS) in 1978-1999. Non-participation in CRC screening was analyzed with Poisson regression as incidence rate ratios (IRR) with 95% confidence intervals (95% CI). Of all persons invited for CRC screening (79 871 men and 80 891 women) 35% of men and 21% of women refused. Of those invited for screening, 2456 men (3.1%) and 2507 women (3.1%) were also invited to the HBS. Persons, who declined HBS, were also more likely to refuse CRC screening (men IRR 1.40, 95% CI 1.26-1.56, women 1.75, 1.52-2.02) compared to HBS participants. Never married persons had about a 75% higher risk for refusing than married ones. The youngest age group (60 years) was more likely to refuse screening than the older age groups (62 or >64 years). Smoking was associated with non-participation in screening (current smokers, men: IRR 1.32, 95% CI 1.05-1.67, women: 2.10, 1.61-2.73). Participation in CRC screening was affected by gender, age, and marital status. Persons, who refused the HBS, were also more likely to refuse CRC screening. Smoking was a risk factor for non-participation in CRC screening.


A synthetic heptasaccharide reveals the capability of a monoclonal antibody to read internal epitopes of a polysaccharide antigen.
The binding of the synthetic heptasaccharide,beta-D-Galp-(1----3)-beta-D-Galp-(1----6)-beta-D-Galp-(1 ----6)-beta-D-Galp-(1----6)-beta-D-Galp-1-OCH3 (10) with two monoclonal IgAs of the X24 gene-family has been investigated. The ligand 10 was synthesized by silver triflate mediated coupling of O-(2,3,4,6-tetra-O-benzoyl-beta-D-galactopyranosyl)-(1----3)-O-(2,4,6,-t ri-O-benzoyl-beta-D-galactopyranosyl)-(1----3)-2,4,6-tri-O-benzoyl-alpha -D-galactopyranosyl chloride (5) to the benzoylated, all-beta-(1----6)-linked methyl galactotetraoside 13, having O-6(4) free, followed by debenzoylation of the formed, fully protected methyl galactoheptaoside. The blockwise synthesis of the nucleophile 13 from readily available monosaccharides, and the synthesis of 5 from the corresponding beta-1-O-benzoylated trisaccharide, is also described. Heptasaccharide 10 binds with the (1----6)-beta-D-galactan-specific monoclonal antibodies X-24 and J539 with essentially the same Ka-values (5.4 x 10(5) M-1 and 6.4 x 10(5) M-1, respectively) as does the methyl beta-glycoside of all-beta-(1----6)-linked galactotetraose 14 (5.7 x 10(5) M-1 and 5.9 x 10(5) M-1, respectively). Of the series of homologous oligosaccharides studied previously (di- through a hexa-saccharide), 14 was found to show the highest affinity of interaction with both these immunoglobulins. The beta-(1----3)-linked galactotriose, which forms the bulky terminus of 10, does not appear to bind to these IgA. Thus, the observation that the affinity of 10 is the same as that of 14 confirms that these immunoglobulins bind internal tetrasaccharide sequences of the antigenic (1----6)-beta-D-galactopyranan.


Role of the conduction system in the endocardial excitation spread in the right ventricle.
The role of the Purkinje network in the excitation sequence in the endocardial surface of the right ventricle was studied using an isolated perfused canine preparation. The preparation was electrically stimulated at the proximal right bundle branch, and the activation time was mapped using contiguous bipolar electrodes or a microelectrode, or both. The earliest activation of muscle was observed at the junction between the ventricular septum and the free wall in front of the anterior papillary muscle. After the initial activation, the spread of ventricular muscle excitation in the free wall was essentially radial at a mean (+/- standard deviation) conduction velocity of 1.67 +/- 0.20 m/s. The activation of muscle in this area was almost always preceded by the activation of Purkinje fibers by 2 to 6 ms. Thus the Purkinje system was considered indispensable for the excitation spread in this area. In the lower third of the septum, the excitation sequence was essentially similar to that of the free wall, indicating a possible contribution of the fast conducting Purkinje system. In contrast, in the upper two thirds of the septum the activation of ventricular muscle spread from apex to base with a significantly delayed conduction velocity of 0.41 +/- 0.88 m/s, and it was not preceded by activation of Purkinje fibers, thus indicating the lack of involvement of the Purkinje system. Functional distribution of the anterior, posterior and lateral branches of the right bundle to the excitation spread of the right ventricular endocardial muscle was confirmed by the selective transection of one of these special conducting fibers, which suggested the etiologic significance of injury to each branch of the right bundle as a cause of various electrocardiographic patterns of incomplete right bundle branch block.


Metal-backed versus all-polyethylene tibias in megaprostheses of the distal femur.
In megaprostheses, the tibial component is rarely a source of failure. The evolution of these implants has followed standard arthroplasty trends moving from majority use of all-polyethylene tibias (APT) to high volume use of metal-backed tibial (MBT) components. We report the results of 72 endoprostheses using either MBT (n = 42) or APT (n = 30) implanted between 1994 and 2006. Failures of the implant related to the tibial component were isolated, and 5-year survival of the tibial implant of the MBT cohort was 94%, and for the APT cohort, 87% (P = .39). The difference in tibial component failures between the 2 groups was not statistically significant (Pearson χ(2) = 0.1535, P = .6952). Revision rates for the entire implant and infection rates were not significantly different between the 2 groups.


Transperineal magnetic resonance image guided prostate biopsy.
We report the findings of a transperineal magnetic resonance image (MRI) guided biopsy of the prostate in a man with increasing prostate specific antigen who was not a candidate for a transrectal ultrasound guided biopsy. Using an open configuration 0.5 Tesla MRI scanner and pelvic coil, a random sextant sample was obtained under real time MRI guidance from the peripheral zone of the prostate gland as well as a single core from each MRI defined lesion. The patient had previously undergone proctocolectomy for ulcerative colitis and, therefore, was not a candidate for transrectal ultrasound guided biopsy. Prior attempts to make the diagnosis of prostate cancer using a transurethral approach were unsuccessful. The random sextant samples contained benign prostatic hyperplasia, whereas Gleason grade 3 + 3 = 6 adenocarcinoma was confirmed in 15% and 25% of the 2 cores obtained from the MRI targeted specimens of 2 defined lesions. The procedure was well tolerated by the patient. Transperineal MRI guided biopsy is a new technique that may be useful in detecting prostate cancer in men with increasing prostate specific antigen who are not candidates for transrectal ultrasound guided biopsy.


The production of F41 fimbriae by piglet strains of enterotoxigenic Escherichia coli that lack K88, K99 and 987P fimbriae.
The enterotoxigenic Escherichia coli strains 1676, 1706, 1751 and KEC96a, which do not produce fimbrial adhesive antigens of the K88, K99 or 987P antigen type reacted both in vitro and in vivo with antiserum to F41 fimbriae in an indirect immunofluorescent antibody technique. Antiserum used to demonstrate material B, an adhesive antigen thought to mediate the adhesive and mannose-resistant (MR) haemagglutinating properties of E. coli strains 1676, 1706 and 1751, reacted in vitro with an F41+ strain. The antiserum also inhibited the MR haemagglutinating activity of F41 antigen and gave an anionic precipitation line in immunoelectrophoresis experiments with an extract containing F41 antigen. The MR haemagglutinating properties of an antigen extract containing material B from E. coli strain 1706 was neutralized by antiserum to F41 fimbriae and by OK antisera to E. coli strains that produce both F41 and K99 fimbriae. These sera also gave an anionic precipitation line with the MR haemagglutinin from E. coli strain 1706 and the MR haemagglutinin gave a line of identity with F41 in gel diffusion experiments with antiserum to F41 fimbriae. OK antisera to K99+ F41- bacteria and OK antisera to K88+ bacteria and 987P+ bacteria did not react with this haemagglutinin. Transmission electron microscopy on the ileum of newborn gnotobiotic piglets infected with E. coli strain 1706 showed irregular, poorly defined filamentous material surrounding some,though not all, bacteria but regular fimbrial structures were not visible.(ABSTRACT TRUNCATED AT 250 WORDS)


Template switching during break-induced replication.
DNA double-strand breaks (DSBs) are potentially lethal lesions that arise spontaneously during normal cellular metabolism, as a consequence of environmental genotoxins or radiation, or during programmed recombination processes. Repair of DSBs by homologous recombination generally occurs by gene conversion resulting from transfer of information from an intact donor duplex to both ends of the break site of the broken chromosome. In mitotic cells, gene conversion is rarely associated with reciprocal exchange and thus limits loss of heterozygosity for markers downstream of the site of repair and restricts potentially deleterious chromosome rearrangements. DSBs that arise by replication fork collapse or by erosion of uncapped telomeres have only one free end and are thought to repair by strand invasion into a homologous duplex DNA followed by replication to the chromosome end (break-induced replication, BIR). BIR from one of the two ends of a DSB would result in loss of heterozygosity, suggesting that BIR is suppressed when DSBs have two ends so that repair occurs by the more conservative gene conversion mechanism. Here we show that BIR can occur by several rounds of strand invasion, DNA synthesis and dissociation. We further show that chromosome rearrangements can occur during BIR if dissociation and reinvasion occur within dispersed repeated sequences. This dynamic process could function to promote gene conversion by capture of the displaced invading strand at two-ended DSBs to prevent BIR.


[What do medical students learn in the elective course in Child and Adolescent Psychiatry?].
A course in child and adolescent psychiatry and psychotherapy is optional for medical students within the Medical Curriculum Munich (MeCuMLMU). Aims of the course are to give insight into the specialty of child and adolescent psychiatry and to help students acquire basic skills. The focus is on psychopathology and on communication skills. A course comprising 23 teaching units and limited to twelve students is taught over four days within one week twice per semester. Child and Adolescent Psychiatry is introduced by means of case presentations of children in different age groups, each with externalizing, and internalizing disorders and with developmental delay, and by a clinical round in the teaching hospital affiliated to the University. Case examples of children are presented by video. In group discussions guided by a teacher students learn to formulate a psychopathological status. Role-plays derived from the clinical examples and video-based feed-back provides students with the opportunity to improve their communication skills. The course is evaluated by means of a written examination, in which a psychopathological status must be written down independently. Students and teachers evaluate the seminar in a structured way. Videotapes of the role-plays are analyzed by the teachers after the course. In a sub-sample, a follow-up evaluation was carried out six months later. The seminar offers an excellent opportunity to introduce medical students to child and adolescent psychiatry and to recruit and inspire a future generation of child and adolescent psychiatrists.


Ultrasound-guided axillary plexus block in a child with dystrophic epidermolysis bullosa.
We report the use of ultrasound-guided axillary brachial plexus block in a child with dystrophic epidermolysis bullosa needing surgical treatment of the right hand. The regional anaesthesia was used in association with sedation/ anaesthesia. This technique is suitable for these difficult patients because it can minimise the risk of new bullae formation due to palpation of landmarks or unintentional intra- or subcutaneous injections. Initial anaesthesia/sedation was provided with sevoflurane until intravenous access was obtained, following which intravenous propofol infusion with ketamine boluses without any invasive airway management was continued for performance of the block and the procedure. This management plan provided good surgical conditions, early postoperative analgesia, minimised stress for the patient and avoided the need to manipulate the airway with instruments and the associated risk of mucosal bullae. The classification and breadth of clinical manifestation of epidermolysis bullosa is complex and briefly summarised. The anaesthetist should clarify the details of a particular patient's form of epidermolysis bullosa, especially in terms of mucosal involvement, as this may greatly influence planning for a procedure.


Effects of chronic cocaine exposure on corticotropin-releasing hormone binding protein in the central nucleus of the amygdala and bed nucleus of the stria terminalis.
The neuropeptide, corticotropin-releasing hormone (CRH), has been shown to play a role in behavioral and neurobiological effects of drugs of abuse. An important modulator of CRH, the CRH binding protein (CRH-BP), has not, on the other hand, been assessed for its role in drug-associated effects. The primary objective of the present experiment was to assess whether prior, chronic exposure to cocaine modulates expression of CRH-BP, and to compare expression of the BP with that of the peptide itself. We assessed CRH-BP and CRH mRNA expression in two brain regions where CRH is known to affect responses to drugs of abuse; namely, the central nucleus of the amygdala (CeA) and bed nucleus of the stria terminalis (BNST). Male Long-Evans rats were given 14 daily injections of cocaine (30 mg/kg, i.p.) or saline. One, 3, 10, 28, or 42 days post-treatment, animals were killed and adjacent brain sections through the CeA and BNST were processed for CRH-BP and CRH by in situ hybridization. In the CeA, cocaine pre-exposure increased both CRH and CRH-BP mRNA expression 1 day post-treatment. In the dorsal BNST, cocaine pre-exposure elevated levels of CRH-BP, but not CRH, mRNA 3 days post-treatment. Taken together, the results suggest that withdrawal-induced changes in the expression of the CRH-BP, and CRH itself, are relatively short-lived and that a dysregulation in basal expression of either gene is not likely responsible for long-lasting behavioral effects noted with cocaine and other drugs of abuse.


PEALD of HfO2 Thin Films: Precursor Tuning and a New Near-Ambient-Pressure XPS Approach to in Situ Examination of Thin-Film Surfaces Exposed to Reactive Gases.
A bottom-up approach starting with the development of new Hf precursors for plasma-enhanced atomic layer deposition (PEALD) processes for HfO2 followed by in situ thin-film surface characterization of HfO2 upon exposure to reactive gases via near-ambient-pressure X-ray photoelectron spectroscopy (NAP-XPS) is reported. The stability of thin films under simulated operational conditions is assessed, and the successful implementation of HfO2 dielectric layers in metal-insulator-semiconductor (MIS) capacitors is demonstrated. Among the series of newly synthesized mono-guanidinato-tris-dialkyl-amido class of Hf precursors, one of them, namely, [Hf{η2-(iPrN)2CNEtMe}(NEtMe)3], was representatively utilized with oxygen plasma, resulting in a highly promising low-temperature PEALD process at 60 °C. The new precursors were synthesized in the multigram scale and thoroughly characterized by thermogravimetric analyses, revealing high and tunable volatility reflected by appreciable vapor pressures and accompanied by thermal stability. Typical ALD growth characteristics in terms of linearity, saturation, and a broad ALD window with constant growth of 1.06 Å cycle-1 in the temperature range of 60-240 °C render this process very promising for fabricating high-purity smooth HfO2 layers. For the first time, NAP-XPS surface studies on selected HfO2 layers are reported upon exposure to reactive H2, O2, and H2O atmospheres at temperatures of up to 500 °C revealing remarkable stability against degradation. This can be attributed to the absence of surface defects and vacancies. On the basis of these promising results, PEALD-grown HfO2 films were used as dielectric layers in the MIS capacitor device fabrication exhibiting leakage current densities less than 10-7 A cm-2 at 2 MV cm-1 and permittivities of up to 13.9 without postannealing.


Socialization and individual antecedents of adolescents' and young adults' moral motivation.
Socialization and individual differences were examined as antecedents of moral motivation in representative samples of 15-year-old adolescents (N = 1,258; 54% female) and 21-year-old young adults (N = 584; 53% female). The adolescents' primary caregivers (N = 1,056) also participated. The strength of moral motivation was rated by participants' responses to two hypothetical moral dilemmas in terms of action decisions, emotion attributions, and justifications. Socialization was measured by the perceived quality of friendship, parent-child relationships, and educational background. The importance attached to social justice and various personality traits were also assessed. Adolescents' moral motivation was positively associated with the quality of their parent-child relationship and the importance of social justice. Young adults' moral motivation was predicted by the perceived quality of friendships, the importance of social justice, and agreeableness. For both groups, moral motivation was greater in females. The theoretical implications of the findings for the development of moral motivation are discussed.


Investigations on gene copy number, introns and chromosomal arrangement of genes encoding the fucoxanthin chlorophyll a/c-binding proteins of the centric diatom Cyclotella cryptica.
The gene arrangement, existence of introns and the number of gene copies of genes (fcps) encoding fucoxanthin chlorophyll a/c-binding proteins (Fcps) of the centric diatom Cyclotella cryptica were investigated by polymerase chain reaction (PCR), Southern blotting and denaturing gradient gel electrophoresis (DGGE) experiments. PCR-mediated amplification of the fcp genes using chromosomal DNA as template demonstrated the absence of introns within the amplified regions. Clustering of genes could not be demonstrated in these experiments. Digestion of chromosomal DNA of Cy. cryptica followed by Southern blotting and hybridization with specific fcp probes revealed minimum and maximum values of 12 and 20, respectively, for the gene copies. In addition, the DGGE technique confirmed and strengthened the results obtained from Southern blotting experiments as amplification of gene fragments from genomic DNA with different sets of specific primers revealed values of 21 and 23, for the minimum and maximum gene copy number, respectively.


Successful weaning from cardiopulmonary bypass with central venous prostaglandin E1 and left atrial norepinephrine infusion in patients with acute pulmonary hypertension.
Postoperative pulmonary hypertension increases the mortality risk in cardiac surgery. We have used central venous prostaglandin E1 (PGE1) and left atrial norepinephrine (NE) infusion to wean from cardiopulmonary bypass (CPB) patients with refractory postoperative pulmonary hypertension. Observational, nonrandomized study. Department of Cardiac Surgery in a university hospital. We studied 10 nonconsecutive American Society of Anesthesiologists III and New York Heart Association class III-IV patients with postoperative pulmonary hypertension and low cardiac output syndrome preventing separation from CPB. Patients received right atrial PGE1 (31.5 +/- 6.26 ng/kg/min) and left atrial NE (0.11 +/- 0.02 microg/kg/min) infusion. Hemodynamic data were obtained before CPB (T0), after CPB under maximal inotropes and vasodilator infusion (T1), 10 mins (T2) and 12 hrs (T3) after PGE1 and NE infusion, and 48 hrs after withdrawal of PGE1 and NE (T4). All patients were successfully weaned from CPB and survived. The biatrial infusion of PGE1 and NE caused a dramatic reduction in mean pulmonary artery pressure (from 42.8 +/- 5.1 mm Hg at T1 to 28.5 +/- 2.6 mm Hg at T2 and 20.5 +/- 2.0 mm Hg at T4), pulmonary vascular resistance index (from 1158 +/- 269 dyne x sec/cm5 x m2 at T1 to 501 +/- 99 dyne x sec/cm5 x m2 at T2 and 246 +/- 50 dyne x sec/cm5 x m2 at T4), and pulmonary-to-systemic vascular resistance index ratio (from 0.61 +/- 0.17 at T1 to 0.20 +/- 0.04 at T2 and 0.11 +/- 0.03 at T4). Cardiac index increased from 1.7 +/- 0.2 L/min/m2 at T1 to 2.3 +/- 0.2 L/min/m2 at T2 and 2.9 +/- 0.1 L/min/m2 at T4. In patients with refractory postoperative pulmonary hypertension, the combined administration of low-dose PGE1 in the right atrium and NE in the left atrium is an effective means to wean patients from cardiopulmonary bypass.


[Effects of thiopental and propofol on suppressor T lymphocyte activity and noradrenaline release].
The effects of thiopental and propofol on lymphocyte suppressor T activity were studied in the basal state and after 20 min, 24 hours, and 4 days of anesthesia induction in 20 patients undergoing gynaecologic surgery. Both drugs induced a decrease in lymphocyte suppressive T activity which recovered after 4 days and tended to be larger, although not significantly, with thiopental. Serum noradrenaline concentration significantly increased after two hours of propofol anesthesia and after 20 min and 2 hours of thiopental administration. These results demonstrate that the relationship between lymphocyte suppressive T activity and noradrenaline corresponds theoretically to anesthesia deepness.


Assessment of the Safety and Efficacy of Prolapsed Orbital Fat Resection During Involutional Entropion Repair.
To assess the recurrence rate of involutional entropion in patients treated with a combined approach including a modified Bick procedure, excision of preseptal orbicularis muscle, and conservative resection of prolapsed orbital fat. A retrospective chart review of patients undergoing repair of involutional entropion with the combined procedure including orbital fat resection and a second group with standard entropion repair without orbital fat resection was performed. Only patients with follow-up greater than 6 months were included in the study. Seventy eyelids of 54 patients met all inclusion criteria for the combined procedure group over a 9-year period from 2008 to 2016. Average follow-up was 46.9 months. There was a documented recurrence of entropion in 1 eyelid during the follow-up period (1.4%). The remaining 69 cases had successful subjective and objective results without need for any additional procedures. In the group undergoing entropion repair without fat resection, 22 eyelids of 19 patients had the required follow-up period with a recurrence rate of 4.5% (p > 0.05). The authors demonstrate good surgical success with a combined approach of a modified Bick procedure, preseptal orbicularis excision, and conservative orbital fat resection. Conservative fat resection during entropion repair was found to be safe, and the combined procedure was found to be effective with a rate of recurrent entropion of 1.4% on extended follow-up.


[Clinical usefulness of scintigraphy with 99m technetium phosphates in rhabdomyolysis].
We performed bone scans with 99mTechnetium phosphates in 15 cases of clinically suspected rhabdomyolysis admitted to Chigasaki Tokushukai Hospital. Whole body scans were performed within 5 days from the onset of illness or admission. Accumulation of the radioactivity in the skeletal muscle was revealed in 13 of the 15 cases and the involved muscle groups were visualized vividly. Etiologies of rhabdomyolysis were diverse, ranging from malignant syndrome to sepsis. Myocardial concentration was absent in all of the cases. Renal concentration of the isotope was seen in cases where the degree of rhabdomyolysis was higher and renal impairment was present. We conclude that 99mTechnetium phosphate bone scan is useful in clinically suspected rhabdomyolysis as a diagnostic test and as a test to localize and quantitate the muscular involvement.


Asialoprotein uptake by liver cells: immunofluorescence microscopy.
Uptake of asialoproteins by hepatocytes causes a change in the intracellular pattern of immunofluorescence. Control cells display a peripheral fluorescence which probably represents nascent proteins. Dark nonfluorescent areas, that presumably contain glycogen, are located around the nucleus. In contrast, liver cells from rats injected with asialoproteins display a pancytoplasmic fluorescence due to an influx of endocytotic vesicles.


Temporal trends of organochlorine pesticides in prawn (Macrobrachium nipponense) from Lake Kasumigaura, Japan, during 1978-2000.
Temporal trends of organochlorine pesticides such as beta-hexachlorocyclohexane (beta-HCH), hexachlorobenzene (HCB), and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE), were determined in freshwater prawn (Macrobrachium nipponense) collected from Lake Kasumigaura in 1978 to 2000. The organochlorine pesticides elucidated a 72.4% decrease in beta-HCH, from 42 (1978) to 11.6 ng/g fat (2000); an 89.6% decrease in HCB, from 1.64 (1978) to 0.17 ng/g fat (2000); and an 87.3% decrease in p,p'-DDE, from 97.5 (1978) to 12.4 ng/g fat (1992). After organochlorine pesticide prohibition in 1971, the declining trend of beta-HCH, HCB, and p,p'-DDE concentrations persisting in the prawns could be approximated by exponential equations.


Pack palsy.
A case of 'Pack Palsy' in a previously fit soldier caused by incorrect adjustment of the strapping of his pack is described. The resulting disability was severe and recovery, although complete, was prolonged. Realization of the potential for brachial plexus injury, particularly in the combat situation, when the duration of march and the rough terrain cannot be varied is strongly emphasised. The mechanics as well as the two different sites of injury are described.


Activation and inducer subset phenotype of the lymphocytic infiltrate around epidermally derived tumors.
An in situ analysis of the mononuclear cell infiltrate found in association with a range of benign, premalignant, and malignant epidermal tumors is described. The predominant cell phenotype was that of the recently described immunoregulatory helper/inducer T lymphocyte. A large number of lymphocytes expressed antigens associated with cellular activation, suggesting an ongoing immunologic response by the host against the tumor, although evidence of in situ proliferation of these cells was lacking. These findings suggest that the infiltrate found in association with cutaneous tumors does not represent passive accumulation of lymphocytes from the circulation but rather an active antitumor response.


Serial lactate determinations during circulatory shock.
The time course of lactacidemia was studied prospectively in 17 patients during fluid resuscitation for an episode of noncardiogenic shock, in 5 patients after grand mal seizures, and in 5 patients after successful CPR for cardiac arrest. The 9 patients in whom shock was reversed with fluid administration demonstrated a regular decrease in lactate concentrations, which exceeded 5% of the initial value during the first 60 min of treatment. In the other patients who expired despite similar therapy, lactacidemia was not significantly affected. During circulatory shock, repeated lactate determinations represent a more reliable prognostic index than an initial value taken alone. Changes in lactate concentration can provide an early and objective evaluation of the patient's response to therapy.


Usability of the middle temporal vein as a recipient vessel for free tissue transfer in skull-base reconstruction.
In skull-base reconstruction, finding appropriate recipient veins is difficult if the patient has undergone previous craniotomy or requires multiple drainage vessels, because of postoperative scarring and the limited number of veins in the temporal region. Therefore, we have used the middle temporal vein (MTV) to overcome these problems. We examined the presence and caliber of the MTV in 12 patients undergoing skull-base reconstruction. The MTV was identified in all cases and used for reconstruction, alone or with the superficial temporal vein (STV), in 8 patients without postoperative flap loss and was only measured in 4 patients. The caliber of the MTV was significantly greater than that of the STV, and there was no significant difference between the usage of the MTV and STV in the length of reconstruction time. Therefore, the MTV is of an appropriate caliber, and its use does not require complicated procedures as alternative recipient vessels.


Functional modulation of choroid plexus epithelial clusters in vitro for tissue repair applications.
One of the primary obstacles in the restoration or repair of damaged tissues is the temporospatial orchestration of biological and physiological events. Cellular transplantation is an important component of tissue repair as grafted cells can serve as replacement cells or as a source of secreted factors. But few, if any, primary cells can perform more than a single tissue repair function. Epithelial cells, derived from the choroid plexus (CP), are an exception to this rule, as transplanted CP is protective and regenerative in animal models as diverse as CNS degeneration and dermal wound repair. They secrete a myriad of proteins with therapeutic potential as well as matrix and adhesion factors, and contain responsive cytoskeletal components potentially capable of precise manipulation of cellular and extracellular niches. Here we isolated CP from neonatal porcine lateral ventricles and cultured the cells under a variety of conditions to specifically modulate tissue morphology (2D vs. 3D) and protein expression. Using qRT-PCR analysis, transmission electron microscopy, and gene microarray studies we demonstrate a fine level of control over CP epithelial cell clusters opening further opportunities for exploration of the therapeutic potential of this unique tissue source.


A multi-district audit against national guidelines for the management of uncomplicated genital Chlamydia trachomatis infection.
A regional audit group in genitourinary medicine (GUM) developed a method to assess their practice using peripatetic audit workers. An audit using 2 audit proformas recorded information relating to an agreed selection of standards contained within the national guidelines for the management of uncomplicated genital chlamydial infection. An audit worker (ADP) reviewed patient records of a sample of cases. Nine GUM clinics throughout the Yorkshire region participated in the audit; 489 cases out of a total annual workload of 2358 cases positively diagnosed as uncomplicated chlamydial infection were reviewed. Variations in compliance with the standards for confirmation of test results and the time from diagnosis to treatment were seen. Recording of discussions, advice and contact tracing activity were limited or separated from the main patient record, making assessment of practice difficult. Post-audit meetings of the group led to action on these areas and commitment to re-audit with the same standards and methods.


Simultaneous measurement of the frequencies of intrachromosomal recombination and chromosome gain using the yeast DEL assay.
The yeast DEL assay measures the frequency of intrachromosomal recombination between two partially-deleted his3 alleles on chromosome XV. The his3Delta alleles share approximately 400bp of overlapping homology, and are separated by an intervening LEU2 sequence. Homologous recombination between the his3Delta alleles results in deletion of the intervening LEU2 sequence (DEL), and reversion to histidine prototrophy. In this study we have attempted to further extend the use of the yeast DEL assay to measure the frequency of chromosome XV gain events. Reversion to His(+)Leu(+) in the haploid yeast DEL tester strain RSY6 occurs upon non-disjunction of chromosome XV sister chromatids, coupled with a subsequent DEL event. Here we have tested the ability of the yeast DEL assay to accurately predict the aneugenic potential of the diversely-acting, known or suspected aneugens actinomycin D, benomyl, chloral hydrate, ethyl methanesulfonate (EMS), methyl methanesulfonate (MMS), and methotrexate. Actinomycin D and benomyl strongly induced aneuploidy. EMS and methotrexate modestly induced aneuploidy, while chloral hydrate and MMS failed to illicit any significant induction. In addition, by FACS-analysis of DNA content it was shown that the majority of both spontaneous- and chemically-induced His(+)Leu(+) revertants were heterodiploid. Thus, our results indicate endoreduplication of almost entire chromosome sets as a major mechanism of aneuploidy induction in haploid Saccharomyces cerevisiae.


Habitat damage, marine reserves, and the value of spatial management.
The biological benefits of marine reserves have garnered favor in the conservation community, but "no-take" reserve implementation is complicated by the economic interests of fishery stakeholders. There are now a number of studies examining the conditions under which marine reserves can provide both economic and ecological benefits. A potentially important reality of fishing that these studies overlook is that fishing can damage the habitat of the target stock. Here, we construct an equilibrium bioeconomic model that incorporates this habitat damage and show that the designation of marine reserves, coupled with the implementation of a tax on fishing effort, becomes both biologically and economically favorable as habitat sensitivity increases. We also study the effects of varied degrees of spatial control on fisheries management. Together, our results provide further evidence for the potential monetary and biological value of spatial management, and the possibility of a mutually beneficial resolution to the fisherman-conservationist marine reserve designation dilemma.


Patient information after ruptured intracranial aneurysm.
This paper reports an investigation into the effects of increased information for patients treated for intracranial aneurysm rupture. Intracranial aneurysm rupture is a grave condition that requires immediate care. It can be treated in two different ways, by surgery or by endovascular procedure. Intracranial aneurysm rupture can mean great changes in life, both for the patient and their spouse or relatives. An intervention study was conducted using a quasi-experimental design. Participants were recruited consecutively over a period of 12 months and consisted of 62 patients treated for intracranial aneurysm rupture at a Swedish neurosurgical clinic. They were divided into two groups: an intervention group, who received written and oral information, and a comparison group, who received only oral information. Self-report questionnaires were sent to patients' homes 1-3 months after the aneurysm rupture. The questionnaires consisted of one study-specific instrument with questions about understanding of the information given and the State-Trait Anxiety Inventory, which measures worry or anxiety. The intervention group considered that the information that they received was somewhat easier to understand and that it corresponded more closely to their needs, compared with the comparison group. The majority of patients in both groups expressed a need for more and improved information. Levels of anxiety were high for the majority of patients, but no significant difference was evident between groups. Furthermore, the results showed that the majority of patients were given information without their spouse or relatives being present. Increased information seems to be needed for these patients. There is a need to continue the work to improve information-giving to them and their relatives.


Quantitation and Confirmation of Chloramphenicol, Florfenicol, and Nitrofuran Metabolites in Honey Using LC-MS/MS.
This paper describes a rapid and robust method utilizing a single liquid-liquid extraction for the quantitation and confirmation of chloramphenicol, florfenicol, and nitrofuran metabolites in honey. This methodology combines two previous extraction methods into a single extraction procedure and utilizes matrix-matched calibration standards and stable isotopically labeled standards to improve quantitation. The combined extraction procedure reduces the average extraction time by >50% when compared with previously used procedures. The drug residues were determined using two separate LC-tandem MS conditions. Validation of all the analytes was performed, with average quantitation ranging from 92 to 105% for all analytes and the RSDs for all analytes being ≤12%.


Shear-induced tilt in smectic-A elastomers.
Smectic-A elastomers combine the positional long-range order of mesogenic molecules in one dimension with the rubber elasticity of a polymer network. While the influence of uniaxial mechanical fields on the phase structure has been investigated intensively during recent years, the impact of shear forces on the orientation of mesogens remains unclear. We present x-ray experiments under shear strain, showing an induced macroscopic tilt depending on the applied shear angle and geometry of the setup.


[Comparison of vitamin B6 status of gravid and nongravid rats with varying vitamin B6 supplements].
In a two-factorial experiment the influence of graded vitamin B6 supplements on the vitamin B6 status of pregnant and nonpregnant rats was examined. Additionally the question concerning a vitamin B6 super-retention in pregnancy should be investigated. The experiment was carried out with 69 female SPF-Sprague-Dawley rats. Nine rats served as controls and were killed at the beginning of the experiment. On the first experimental day half of the remaining animals were mated at an average body weight of 210 g. The rats were then divided into five dietary groups, each containing 6 gravid and 6 nongravid animals. Throughout the experiment the rats received a semisynthetic casein-starch diet, containing 1, 6, 12, 24, and 48 mg vit. B6/kg respectively. The trial ended at day 19 of pregnancy. Liver, right and left gastrocnemius muscle and the remaining carcass (without the intestinum and the reproductive product of the pregnant animals) were microbiologically analysed for their vitamin B6 contents. The vitamin B6 status of the liver, which contained an average of 8.4 micrograms vit. B6/g fresh matter (FM) was not influenced by pregnancy. In muscle and carcass, however, pregnancy caused significantly reduced vitamin B6 levels of 4.8 and 2.6 micrograms vit. B6/g FM. Compared to the concentrations of the nongravid animals the values of the gravid rats were decreased by 6 and 7% respectively. The vitamin B6 supply of 1 mg/kg diet caused significantly lowered vitamin B6 concentrations in muscle and carcass of all animals. Intake levels of more than 6 ppm vitamin B6, however, did not further improve the vitamin B6 status of these organs. The carcass was only poorly affected by the vitamin B6 supplementations. Significant differences in vitamin B6 concentrations were only found between the 1 and 48 ppm vitamin B6 treatment. The whole vitamin B6 pool of the maternal organism, except the reproductive product, decreased in pregnancy from an average of 651 to 596 micrograms vitamin B6. Because of these results a super-retention could not be proved for vitamin B6. Moreover, a recommendation for the optimal vitamin B6 requirement in pregnancy was derived from the present results. Accordingly a supply of 6 mg vit. B6/kg diet, equivalent to a daily intake of 80 micrograms vitamin B6, is thought to be adequate to ensure an optimal vitamin B6 status in pregnant rats.


Recurrent posttraumatic urethro-vaginal fistula: a new application for ASTRA.
The authors describe the results of an application of the surgical technique called ASTRA (anterior sagittal transrectal approach) in a 16-year-old girl with recurrent urethro-vaginal fistula. The young girl had a posttraumatic urethro-vaginal fistula. It recurred after 4 operations by a direct vaginal approach before definitive correction with the ASTRA. Three years after the operation the patient has remained well with complete healing and no fistula recurrence confirmed by a voiding cystourethrogram and urodynamic and rectal manometric tests. This report suggests that ASTRA is a useful method of treating acquired or developmental anomalies of the perineal region.


Reactive oxygen species: physiological roles in the regulation of vascular cells.
Reactive oxygen species (ROS) are now appreciated to play several important roles in a number of biological processes and regulate cell physiology and function. ROS are a heterogeneous chemical class that includes radicals, such as superoxide ion (O2(•-)), hydroxyl radical (OH(•)) and nitric oxide (NO(•)), and non-radicals, such as hydrogen peroxide (H2O2), singlet oxygen ((1)O2), hypochlorous acid (HOCl), and peroxynitrite (NO3 (-)). In the cardiovascular system, besides playing a critical role in the development and progression of vasculopathies and other important pathologies such as congestive heart failure, atherosclerosis and thrombosis, ROS also regulate physiological processes. Evidence from a wealth of cardiovascular research studies suggests that ROS act as second messengers and play an essential role in vascular homeostasis by influencing discrete signal transduction pathways in various systems and cell types. They are produced throughout the vascular system, regulate differentiation and contractility of vascular smooth muscle cells, control vascular endothelial cell proliferation and migration, mediate platelet activation and haemostasis, and significantly contribute to the immune response. Our understanding of ROS chemistry and cell biology has evolved to the point of realizing that different ROS have distinct and important roles in cardiovascular physiology. This review will outline sources, functions and molecular mechanisms of action of different ROS in the cardiovascular system and will describe their emerging role in healthy cardiovascular physiology and homeostasis.


[Solitary renal metastasis of primary esophageal cancer].
We present an unusual case of single kidney metastasis from an primary esophageal neoplasm. Its main clinical and diagnostic topics are described. They made us consider him as a good candidate for surgery. The pathological study of the nephrectomy specimen was surprising. The postoperative period was unfortunate, however.


A novel one-dimensional complex: catena-poly[[manganese(III)-di-mu-2-[(2-hydroxyethyl)iminomethyl]phenolato-kappa2O1,N:kappaO2;kappaO2:kappa2O1] chloride].
In the title one-dimensional complex, [[Mn(III)(C9H10NO2)2]Cl]n, the Schiff base ligand 2-[(2-hydroxyethyl)iminomethyl]phenolate (Hsae-) functions as both a bridging and a chelating ligand. The Mn(III) ion is six-coordinated by two N and four O atoms from four different Hsae- ligands, yielding a distorted MnO4N2 octahedral environment. Each [Mn(III)(Hsae)2]+ cationic unit has the Mn atom on an inversion centre and each [Mn(III)(Hsae)2]+ cation lies about another inversion centre. The chain-like complex is further extended into a three-dimensional network structure through Cl...H-O hydrogen bonds and C-H...pi contacts involving the Hsae- rings.


[Influence of the earthworm Lumbricus terrestris on soil solution complexation capacity].
Four soil samples highly contaminated with metals of urban and mine origin (SE1, SE2, SM1, SM2) and having different physico-chemical proprieties were selected to study copper complexation capacity (LT) of soil solution. The effect of Lumbricus terrestris on copper complexation capacity of soil solution was investigated on SE1 and SE2. The complexation capacity was estimated by amperometric titration of soil solution by copper. Free hydrated cation and labile complexes of copper were determined by DPASV. The results show that the copper complexation capacity variation depends on the physico-chemical characteristics of soils, particularly pH. Thus, the values of copper complexation capacity are 0; 0.6 x 10(-7); 1.8 x 10(-7) and 5.5 x 10(-7) mol l-1 respectively for SM2; SM1; SE1 and SE2 which are pH 5; 5.4; 6.5 and 7.4. Based on these results, the bioavailability levels of heavy metals show the following pool ranking: SM2 > SM1 > SE1 > SE2. The copper complexation capacity of soil solution increases with the soil disturbance by Lumbricus terrestris. This is more obvious when the time of disturbance by lumbrics is longer. Indeed, average values determined for 1 month and 3 months are 3.8 x 10(-7) and 7.8 x 10(-7) mol l-1 for SE1; 7.7 x 10(-7) and 15.2 x 10(-7) mol l-1 for SE2 respectively. It seems that the action of earthworm on soil can contribute to the decrease of bioavailability of heavy metals, particularly copper.


Interactive program for spectral and area analysis of compound action potentials of A-fiber and C-fiber.
An interactive program was described to correct the baseline wandering of the compound action potentials (CAPs) of C-fiber, to calculate the area and the peak amplitude of CAPs, and to analyze their spectral distribution. Using this program, we found the optimal bandpass of the filter for recording CAPs to be from 10 Hz to 3 kHz.


Longterm follow-up of onchocerciasis patients in Latin America after treatment and retreatment with amocarzine. Preliminary results.
Amocarzine has been reported to have onchocercacidal effects. Four months posttherapy the majority of adult worms were dead or moribund. The effect of skin microfilariae lasted up to one year as reflected by markedly reduced microfilaridermia. Since the duration of the onchocercacidal effect of amocarzine beyond one year was unknown and since such an effect may influence the planning of future control strategies, efforts were made to follow-up the already treated amocarzine patients for a second year. The present study from Latin America showed that various amocarzine drug regimens produced a prolonged reduction of microfilaridermia at the end of the second year following the initial therapy, the best levels were about 7-17% of the initial parasite load in the skin for some three days amocarzine regimens. Such an effect occurring in a transmission area of onchocerciasis in Latin America provides additional, although indirect, evidence of a macrofilaricidal effect of amocarzine. Similar experiences of a prolonged amocarzine effect on skin microfilariae has also been observed in West Africa (Ghana, Mali). Preliminary results of retreatment schedules at the start of the third year post-initial therapy showed that simplified postprandial dose regimen of one or two days were well tolerated. It is premature at the time of this report to judge upon their ultimate efficacy, but they had significantly reduced levels of moderate microfilaridermia.


Dopamine-beta-hydroxylase-like immunoreactive neurons in two insect species, Calliphora erythrocephala and Periplaneta americana.
The localization of dopamine-beta-hydroxylase in the cephalic central nervous system of the blowfly (Calliphora erythrocephala) and the cockroach (Periplaneta americana) was investigated. Immunoreactive neurons were demonstrated in both species. The results were compared with the known distribution of catecholamines in the brain of both species. In certain cell groups and neuropilar regions of both species D beta H-immunoreactivity coincides with the presence of catecholamines. Additionally D beta H immunoreactivity was found in several cell bodies and neuropilar regions in which no catecholamines could be detected. A correlation between the presence of octopamine and anti-D beta H labelling was not found. Thus it seems that the D beta H-immunoreactivity neither indicates the presence of octopamine nor is it limited to noradrenaline-containing neurons. Parallel findings in vertebrates are discussed.


Slow-release fluoride devices for the control of dental decay.
Slow-release fluoride devices have been investigated as a potentially cost-effective method of reducing dental caries in those with high risk of disease. To evaluate the effectiveness of different types of slow-release fluoride devices on preventing, arresting, or reversing the progression of carious lesions on all surface types of deciduous and permanent teeth. We searched (up until February 2005) multiple electronic databases (Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE), bibliographic references of identified randomised controlled trials (RCTs), textbooks, review articles, and meta-analyses. Letters were sent to authors of identified RCTs asking for clarifications and unpublished or ongoing research. Relevant journals were handsearched for more recent reports than those obtained from databases. Randomised or quasi-randomised controlled trials (RCTs) comparing slow-release fluoride devices with an alternative fluoride treatment, placebo, or no intervention in all age groups. The main outcomes measures sought were changes in numbers of decayed, missing, and filled teeth or surfaces (DMFT/DMFS in permanent teeth or dmft/dmfs in primary teeth) and progression of carious lesions through enamel and into dentine. Abstracts of all reports identified were considered independently by two review authors and full reports obtained of any potentially relevant articles to allow further assessment for relevance and validity. Data extraction and quality assessment were conducted independently by two and three review authors respectively, with arbitration by the fourth. Where uncertainty existed, authors were contacted for additional information. Only one trial involving 174 children fully met the criteria for inclusion in this review. Although 132 children were still included in the trial at the 2-year completion point, examination and statistical analysis was performed on only the 63 children who had retained the beads. Thirty-one of these were in the intervention group and 32 in the control group. Amongst these 63 children, caries increment was reported to be statistically significantly lower in the intervention group than in the placebo group (mean difference: -0.72 DMFT, 95% confidence interval -1.23 to -0.21 and -1.52 DMFS, 95% confidence interval -2.68 to -0.36) There is some evidence of a caries-inhibiting effect of slow-release fluoride glass beads. This evidence is regarded as weak and unreliable because the results were from participants selected on the basis of bead retention rather than an intention-to-treat analysis.


Wear particulate and osteolysis.
Total joint replacements of the hip and knee are generally highly successful, with satisfactory longevity and clinical results. Using modern biocompatible materials, optimal component design, and meticulous surgical technique, survivorship of cemented or cementless joint replacements is approximately 15 years with more than a 90% probability. The host's biologic response is critical to implant longevity. Particulate disease refers to the host's adverse biologic response to wear debris and byproducts generated from the prosthesis. Initially, emphasis was placed on particulate polymethylmethacrylate (cement disease), but more recently polyethylene wear debris has been underscored. Debris from several materials in sufficient quantities and physicochemical forms, however, can generate an inflammatory cascade resulting in periprosthetic bone destruction (osteolysis), jeopardizing long-term success of the implant.


Effects of alendronate sodium therapy on carotid intima media thickness in postmenopausal women with osteoporosis.
Osteoporosis and cardiovascular disease are major health problems that lead to morbidity and mortality. Bisphosphonates are among the drugs used most frequently worldwide to treat osteoporosis, especially in older women. B-mode ultrasonography has recently become a valuable tool for early diagnosis of atherosclerotic disease because of its ability to measure carotid artery intima media thickness (CIMT). The purpose of the present study was to investigate whether alendronate sodium therapy has an effect on CIMT in postmenopausal women with osteoporosis. A total of 71 postmenopausal women with osteoporosis were evaluated before and after they began taking alendronate sodium; follow-up was provided for an average of 13+/-2 mo. Osteoporosis was diagnosed with the use of dual-energy x-ray absorptiometry, and therapy with alendronate sodium was begun at a dose of 70 mg/wk. For CIMT, B-mode ultrasonography was performed on the right and left middle and distal main carotid arteries. Before alendronate sodium therapy was initiated, the average CIMT value was 0.734+/-0.121 mm; after therapy, the average CIMT was 0.712+/-0.111 mm. This difference was not confirmed to be statistically significant. Treatment of osteoporosis does not seem to have an effect on CIMT, which is an early marker of atherosclerosis.


Arctic research at three levels.
This paper is a posthumous publication of a Steven McNabb's presentation to the 1993 annual meeting of the American Anthropological Association. In it he described how the Social Transitions in the North research project involved explicit cross-cultural contact or participation at three levels: between scientists and public agencies; between scientists and study populations; and between research teams themselves. He explored a few of the entanglements and opportunities that arise in those interactions. Dr. McNabb urged northern researchers to avoid embracing rigid standards, for they will result in more entanglements and fewer opportunities. On the otherhand, if researchers are open-minded, they will be able to treat each dilemma as an opportunity that will make for better science.


Validity of patient-derived disability and clinical data in multiple sclerosis.
Patient-derived historical data are widely employed to make fundamental management decisions in multiple sclerosis, although the validity of the information provided is unclear. The objectives of this study were to determine validity of patient-derived historical data and to describe the utility of a locally relevant, patient-administered questionnaire designed to ascertain current disability and other important disease milestones. A well-described cohort of 99 patients was identified for whom comparable, detailed, prospective longitudinal clinician-derived data were available. Patient-derived data were collected by completion of a standardized questionnaire or telephone interview for comparison. Reliability analysis for current Expanded Disability Status Scale (EDSS) demonstrated an intraclass correlation coefficient of 0.79 between questionnaire and clinician-derived data in 79 patients, with complete agreement in 75.9%. Intraclass correlation coefficient for year of disease onset, diagnosis and onset of secondary progression was 0.86, 0.91 and 0.78, respectively. Time to EDSS >4.0, 6.0 and 8.0 all had an intraclass correlation coefficient of >0.9. Less robust agreement was observed for current disease course (Kappa coefficient 0.71), initial relapse rate (intraclass correlation coefficient 0.37) and clinical features at disease onset (Kappa 0.25). We conclude that self-reported questionnaires can provide reliable current and retrospective data on time-to-disability milestones with high levels of correlation observed for some additional elements, supporting the use of selected components of patient-derived data in clinical practice and for epidemiological studies.


[Anaerobes analysis in 80 cases with ora maxillofacial infections]
OBJECTIVE:To define the infection types of 80 cases of ora-maxillofacial infection and investigate its anaerobes' distribution and the role of the anaerobes' metabolic products in their identification.METHODS:We isolated and cultured anaerobes from the purulent specimen and applied the gasliquid chromatograph (GLC) technique to analyze the anaerobes' metabolic products to define their genera and species in the meantime.RESULTS:Bacteria were isolated from all of the purulent specimen.Isolation rate of bacteria was 100.00% and isolation rate of anaerobes,which distributed in 8 genera,29 species,was 95.00%. The higher detectable rate of them were respectively peptostreptococcus,petococcus,bacteroides,fusobacterium,verillonella,eubacterium. The rate of mixed infection was 80.00%. The proportion ratio of aerobes and anaerobes was 1:1.08.CONCLUSION:Oral-maxillofacial infection mostly belongs to endogenous mixed infection in which anaerobes are preponderant bacteria. GLC technique is a effective,sensitive,selective and specific method for defining anaerobes' genera and species through analyzing their metabolic products. It is a promising and recommendable rapid anaerobes' identification method comparatively at present.


Rapid immunoenzymatic technique for titration of rabies antibodies IgG and IgM.
This report is concerned with the application of the enzyme immunoassay to measure the antibodies in humans vaccinated against rabies or presenting symptoms of rabies without having been vaccinated. By the same technique we identify the IgG and IgM classes of antibodies. The antigen (5 microgram/ml), purified virus, is readily adsorbed into polystyrene tube by passive adsorption. The use of only one dilution for each serum assay (1/200) is particularly suitable for epidemiological studies. Antibody response of subjects in the course of rabies vaccination was an obvious application. After 5 inoculations of tissue culture vaccine the IgM response was poor and late; it was even negative in two cases. The IgG response appeared early on the 7th day. In the same way we tried to follow antibody response in three cases of rabies in man. Seroneutralisation (SN) antibody were not detected at the beginning of the illness. In case 1 antibodies were found on the 12th day, in case 2 on the 7th day and in case 3 on the 8th day. When we assayed the serum samples for immunoenzymatic test, we found that the sera became positive some days earlier: on the 5th for case 1, already on the 1st day for the two others. In each of these three cases the positivity of the test corresponded to the presence of IgM class globulins since IgG detection remained negative as did the SN test. Our results could have some clinical interest concerning future rabies treatment and early diagnosis.


Corticotropin-releasing factor (CRF) antagonist suppresses stress-induced locomotor activity in an amphibian.
Intracerebroventricular (icv) injections of corticotropin-releasing factor (CRF; 25 ng) given to male rough-skinned newts (Taricha granulosa) stimulated locomotor activity tested in a circular arena starting 35 min after the injection. The CRF receptor antagonist, alpha-helical CRF9-41 (ahCRF; 250 or 500 ng), injected icv concurrently with CRF blocked CRF-induced locomotor activity. In contrast, icv injection of ahCRF had no effect on spontaneous locomotor activity. Other studies examined the effect of ahCRF on the elevated locomotor activity that was observed when the animals were stressed (handled or placed in warm water). The CRF antagonist dose dependently attenuated the response to either handling or warm stress tested 2 hr after drug treatment. We also examined the effect of the alpha 2-adrenergic agonist, clonidine, on spontaneous and CRF-induced locomotor activity. Clonidine injected icv dose dependently suppressed spontaneous locomotor activity but not CRF-induced locomotor activity. These studies support the hypothesis that endogenous CRF is involved in mediating stress-induced locomotor activity and indicate that the effects of CRF on locomotor activity are independent of activation of the alpha 2-adrenergic system.


Smoking habits, its forms and impact on pulmonary health in planes of Uttar Pradesh.
A total of 611 rural and 164 urban subjects were studied. Smoking was found more prevalent in urban areas as compared to rural areas. In relation to sex it was more prevalent among urban males and rural females. Bidi was the commonest mode of smoking among rurals, and cigarette in urban population. Pulmonary function test (PFT) analysis proved that smoking causes definite pulmonary functional impairments among smokers. Though its aetiology in producing restrictive impairment remains doubtful and may be additive only but its role in precipitating obstructive impairment is definite in urban smokers. On the contrary rural non-smokers suffer more from the obstructive impairment. Environmental pollution, exposure to toxic fumes and industrial gases in urban areas and organic and inorganic dust exposure in rural areas may be responsible for precipitation of pulmonary function impairments among non-smokers.


Outcome of primary radiocephalic fistula for haemodialysis.
Patient characteristics may help select the most appropriate type of permanent vascular access for haemodialysis. The aim of this study was to assess the influence of patient-related variables on the outcome of radiocephalic fistulas. Over 3 years 107 consecutive patients underwent formation of a radiocephalic fistula for permanent haemodialysis access. Patients receiving prosthetic, ulnar, brachial or secondary fistulas were excluded. Patients were followed prospectively until access failure, transplantation or death, or for a minimum of 6 months (median follow-up 24 months). Primary patency was 69 per cent at 12 months and 56 per cent at 24 months. Endovascular and surgical intervention led to limited improvement in secondary patency to 63 per cent at 24 months. Regression analysis showed that fistula failure was more common in women (P = 0.02), diabetics (P = 0.03) and young patients (P = 0.02). By life-table analysis, primary and secondary patency were significantly better (P = 0.01) for men and non-diabetics, while the outcome was similar for all age groups. One-third of radiocephalic fistulas fail irreversibly within 2 years. Failure is more likely in women and diabetic patients.


Effect of curcumin on the induction of glutathione S-transferases and NADP(H):quinone oxidoreductase and its possible mechanism of action.
This study is to investigate the effect of curcumin on the induction of glutathione S-transferases (GST) and NADP(H):quinone oxidoreductase (NQO) and explore their possible molecular mechanism. The activity of GST, NQO and cellular reduced glutathione (GSH) content were measured by spectrophotometrical methods. Cellular changes in the distribution of NF-E2 related factor 2 (Nrf2) were detected by Western blotting analysis. Nrf2-AREs (antioxidant-responsive elements) binding activity was examined by electrophoretic mobility shift assay (EMSA). Treatment of HT-29 human colon adenocarcinoma cells with curcumin dramatically induced the activity of GST and NQO at the range of 10-30 micromol x L(-1). Curcumin exposure caused a significant increase in cellular GSH content rapidly as early as 3 h. Moreover, curcumin triggered the accumulation of Nrf2 in nucleus, and increased Nrf2 content in ARE complexes. These results demonstrated that induction of GST and NQO activity by curcumin may be mediated by translocation of transcription factor Nrf2 from cytoplasm to nuclear and increased binding activity of Nrf2-ARE complexes.


Evaluation of modified hyaluronic acid in terms of rheology, enzymatic degradation and mucoadhesion.
This study aimed to investigate the properties of modified hyaluronic acid in terms of rheological properties, enzymatic degradation and mucoadhesiveness. Hyaluronic acid (HA) was chemically modified with sulfhydryl ligand cysteine ethyl ester (C) in order to immobilize sulfhydryl groups on the polymeric backbone. MTT assay was performed to evaluate the safety of hyaluronic acid-cysteine ethyl ester (HAC). Rheological and enzymatic degradation studies were accomplished by preparing hydrogels of HA and HAC, respectively. HA served as control. Enzymes such as lysozyme, amylase and hyaluronidase were chosen to perform degradation studies. To study mucoadhesiveness, hydrogels of HA and HAC, respectively, were mixed with mucus and evaluated by rheology. MTT assay indicated no toxicity at all. The rheological assay showed 2.2-fold increase in gelling properties in case of HAC in comparison to HA. Furthermore, it could be shown that HAC was degraded by amylase to a lesser extent of 11.5-fold than HA. After 2 h, HA showed a higher degradation by lysozyme with 67.97% than HAC. Adhesion studies exhibited a 2.17-fold higher mucoadhesion of HAC with mucus compared to HA. These results will open the door for high efficient drug delivery systems based on hydrogels for mucosal application.


Molecular galactose-galectin association in neuroblastoma cells: An unconventional tool for qualitative/quantitative screening.
Galectin decorates the cell membrane and forms an extracellular molecular association with galactoside units. Here, galactoside probes have been used to study galectin expression in neuroblastoma cells. The hypothesis behind this investigation has been that the molecular mechanisms by which glycans modulate neural metastatic cells involve a protein-carbohydrate association, galectin-galactose. Preliminary screening to validate the hypothesis has been performed with galactose moieties anchored to beads. The molecular association has been studied by FACS. In vitro experiments reveal the molecular binding preferences of the metastatic neuroblastoma cells. Ex vivo, the galactose probes discriminate healthy tissues. The unconventional assay in microfluidics used in this study displayed results analogous to the above (GI-LI-N cell capture efficiency overcomes IMR-32). At the point of equilibrium of shear and binding forces, the capture yield inside the chamber was measured to 60 ± 4.4% in GI-LI-N versus 40 ± 2.1% in IMR-32. Staining of the fished cells and subsequent conjugation with red beads bearing the galactose also have evidenced that microfluidics can be used to study and quantify the molecular association of galectin-galactose. Most importantly, a crucial insight for obtaining single-cell qualitative/quantitative glycome analysis has been achieved. Finally, the specificity of the assay performed in microfluidics is demonstrated by comparing GI-LI-N fishing efficiency in galactose and fucose environments. The residual adhesion to fucose confirmed the existence of receptors for this glycan and that its eventual unspecific binding (i.e. due to electrostatic interactions) is insignificant compared with the molecular binding. Identification and understanding of this mechanism of discrimination can be relevant for diagnostic monitoring and for producing probes tailored to interfere with galectin activities associated with the malignant phenotype. Besides, the given strategy has implications for the rational design of galectin-specific ligands.


Sodium-calcium exchange in transverse tubules isolated from frog skeletal muscle.
Transverse tubule vesicles isolated from frog skeletal muscle display sodium-calcium exchange activity, which was characterized measuring 45Ca influx in vesicles incubated with sodium. The initial rates of exchange varied as a function of the membrane diffusion potentials imposed across the membrane vesicles, increasing with positive intravesicular potentials according to an electrogenic exchange with a stoichiometry greater than 2 sodium ions per calcium ion transported. The exchange activity was a saturable function of extravesicular free calcium, with an apparent K0.5 value of 3 microM and maximal rates of exchange ranging from 3 to 5 nmol/mg protein per 5 s. The exchange rate increased when intravesicular sodium concentration was increased; saturation was approached when vesicles were incubated with concentrations of 160 mM sodium. The isolated transverse tubule vesicles, which are sealed with the cytoplasmic side out, had a luminal content of 112 +/- 39 nmol calcium per mg protein. In the absence of sodium, the exchanger carried out electroneutral calcium-calcium exchange, which was stimulated by increasing potassium concentrations in the intravesicular side. Calcium-calcium exchange showed an extravesicular calcium dependence similar to the calcium dependence of the sodium-calcium exchange, with an apparent K0.5 of 6 microM. Sodium-calcium and calcium-calcium exchange were both inhibited by amiloride. The sodium-calcium exchange system operated both in the forward and in the reverse mode; sodium, as well as calcium, induced calcium efflux from 45Ca-loaded vesicles. This system may play an important role in decreasing the intracellular calcium concentration in skeletal muscle following electrical stimulation.


Ly6d-L, a cell surface ligand for mouse Ly6d.
The mouse Ly6 gene family encodes proteins found in lymphocytes and other cells. Some are involved in cell activation; no ligands have been found. A ligand for Ly6d (ThB) was identified on lymphocytes using microspheres loaded with Ly6d and the cDNA isolated from a spleen/thymus library by panning on Ly6d. The Ly6d ligand (Ly6d-L) is a nonglycosylated protein of 9 kDa of broad distribution, rich in cysteine, with no discernable transmembrane sequence. Its N and C termini are on the cell surface, where it associates with a 30 kDa protein. Ly6d-L is homologous with an EGF repeat of Notch.


Removal of dissolved sulfides in aqueous solution by activated sludge: mechanism and characteristics.
Activated sludge recycling has been developed as a novel technique to directly prevent volatile sulfides emission from wastewater influents. In this study, mechanisms and characteristics of dissolved sulfides removal in aqueous solution by activated sludge were investigated. When DO content in water was 0.49mg/L, 70% of removed dissolved sulfides were released back from the activated sludge by lowering pH to 1. The SEM/EDS result revealed that removed sulfur was fixed in activated sludge and the XPS result showed that fixed sulfur had an oxidation state of -2. FTIR results showed that primary amine group (R-NH2) could be one of the radical groups bonding sulfides. All these results verified that sulfides removal by activated sludge is primarily attributed to adsorption, rather than biodegradation, under low DO conditions in 40min. The equilibrium isotherm data fit the Langmuir isotherm model well. The maximum adsorption capacity (q0) ranged in 25-38mg/g at temperatures of 10-40°C. The adsorption kinetic data fit the pseudo-second-order model well. The amounts of adsorbed sulfides at equilibrium (qe) were positively proportional to temperature, initial sulfides concentration and agitation speed. These results indicate that sulfides adsorption could be a chemical sorption or ion exchange process.


Cetacean Toll-like receptor 4 and myeloid differentiation factor 2, and possible cetacean-specific responses against Gram-negative bacteria.
Toll-like receptor 4 (TLR4) and myeloid differentiation factor 2 (MD-2) are essential for recognizing the lipopolysaccharides (LPS) of Gram-negative bacteria. We determined the sequences of cDNAs encoding TLR4 and MD-2 from cetaceans and generated three-dimensional (3D) models for a better understanding of their modes of interaction and LPS recognition. The 3D reconstructions showed that cetacean TLR4 and MD-2 formed a horseshoe-like structure comprised of parallel β-strands and a β-cup structure consisting of two anti-parallel β-sheets, respectively. The (TLR4-MD-2)(2) duplex-heterodimer was shown to form a symmetrical structure. Comparison with the interfaces of the complexes in other mammals revealed that cetacean TLR4s have some amino acid residue substitutions involved in duplex-heterodimer formation and in species variation for LPS recognition. These substitutions in the changed amino acid residues may alter the interaction among TLR4, MD-2, and LPS and modify the TLR4/MD-2 immunological responses.


[Sjögren's syndrome extraglandular expressions].
The Sjögren's syndrome (SS) is an autoimmune disease which causes injury to lacrimal and salivar glands and is characterized by a potential systemic involvement. The present review will treat mainly of SS extraglandular expressions, focusing on scientific literature articles regarding SS implications in gynecology and obstetrics.


Assessment of therapeutic response of Plasmodium falciparum to chloroquine and sulfadoxine-pyrimethamine in an area of low malaria transmission in Colombia.
Although chloroquine (CQ) resistance was first reported in Colombia in 1961 and sulfadoxine-pyrimethamine (SP) resistance in 1981, the frequency of treatment failures to these drugs in Colombia is unclear. A modified World Health Organization 14-day in vivo drug efficacy test for uncomplicated Plasmodium falciparum malaria in areas with intense malaria transmission was adapted to reflect the clinical and epidemiologic features of a low-intensity malaria transmission area in the Pacific Coast Region of Colombia. Patients > or =1 year of age with a parasite density > or =1,000 asexual parasites per microliter were enrolled in this study. Forty-four percent (24 of 54) of the CQ-treated patients were therapeutic failures, including 7 early treatment failures (ETFs) and 17 late treatment failures (LTFs). Four (6%) of 67 SP-treated patients were therapeutic failures (2 ETFs and 2 LTFs). Therapeutic failure in the CQ-treated group was associated with an age <15 years old (P < 0.01), but was not associated with initial parasite density, the presence of CQ or sulfa-containing drugs in urine, or a history of malaria. The high level of therapeutic failures to CQ detected in this study underscores the need and importance of drug efficacy evaluation in the development of a rational national antimalarial drug policy. The relatively low level of therapeutic failures to SP compared with other South American countries raises further questions regarding factors that might have prevented the rapid development of in vivo resistance to this drug combination.