[Transdermal nitroglycerin in stable effort angina. II. Administration of continuous high doses and alternate high-low doses. Absence of tolerance].
Aim of this study was to evaluate the efficacy of 2 different schedules of nitroglycerin (N), given by means of transdermal therapeutic system (TTS): continuous (20 mg patch at 8.00 am and at 8.00 pm NTTS/c) and high/low doses therapy (20 mg patch at 8.00 am and 10 mg at 8.00 pm NTTS/a), respectively. Eighteen volunteers, gave informed, written consent; male patients, aged 57 +/- 2 years, with stable effort angina pectoris, were randomly given, in double-blind condition, NTTS/c, NTTS/a or placebo (PL), each for 1 week period, according to a 3 x 3 latin square design. Bicycle exercise tests were performed on the first and on the last day of each period of the study, 12 hours after the last patch. NTTS/c and NTTS/a increased ischemic threshold and decreased the ischemic depression ST at maximal common work, compared to placebo, without differences between tests performed at 1 and 7 day. In conclusion, NTTS/a showed antiischemic activity after 7 days, so no tolerance was observed in those patients.


Clinical Characteristics of Arteriovenous Malformations of the Head and Neck.
Arteriovenous malformation (AVM) of the head and neck regions show low incidence; hence, studies regarding the causative factors of onset, diagnostic criteria, clinical aspects, treatment methods, and outcomes remain lacking. To share the diagnostic and treatment experiences at the center and to understand the treatments' effect through a retrospective analysis of cases in the past 15 years. The authors included 60 patients with AVM in the head and neck area between January 1999 and September 2014 to investigate diagnostic methods, distributions and locations of lesions, clinical stage, and treatment methods by retrospective evaluation. In all, 3.7% were diagnosed with AVMs of the head and neck. No sex-related differences were observed, and the mean age at diagnosis was 27.6 ± 14.24 years. The left (26 patients, 43%) and V2 sections (33 patients, 55%) of the head and neck were the most frequent locations. Stage II (28 patients, 47%) had the largest distribution. Forty-four patients (73%) showed improvement after sclerotherapy, embolization, and surgical resection. The diagnosis and treatment of AVMs should be approached on a case-by-case basis by gathering opinions from specialists in each department using medical history, physical examination, and imaging results.


Duration of antibody response following vaccination against feline immunodeficiency virus.
Objectives Recently, two point-of-care (PoC) feline immunodeficiency virus (FIV) antibody test kits (Witness and Anigen Rapid) were reported as being able to differentiate FIV-vaccinated from FIV-infected cats at a single time point, irrespective of the gap between testing and last vaccination (0-7 years). The aim of the current study was to investigate systematically anti-FIV antibody production over time in response to the recommended primary FIV vaccination series. Methods First, residual plasma from the original study was tested using a laboratory-based ELISA to determine whether negative results with PoC testing were due to reduced as opposed to absent antibodies to gp40. Second, a prospective study was performed using immunologically naive client-owned kittens and cats given a primary FIV vaccination series using a commercially available inactivated whole cell/inactivated whole virus vaccine (Fel-O-Vax FIV, three subcutaneous injections at 4 week intervals) and tested systematically (up to 11 times) over 6 months, using four commercially available PoC FIV antibody kits (SNAP FIV/FeLV Combo [detects antibodies to p15/p24], Witness FeLV/FIV [gp40], Anigen Rapid FIV/FeLV [p24/gp40] and VetScan FeLV/FIV Rapid [p24]). Results The laboratory-based ELISA showed cats from the original study vaccinated within the previous 0-15 months had detectable levels of antibodies to gp40, despite testing negative with two kits that use gp40 as a capture antigen (Witness and Anigen Rapid kits). The prospective study showed that antibody testing with SNAP Combo and VetScan Rapid was positive in all cats 2 weeks after the second primary FIV vaccination, and remained positive for the duration of the study (12/12 and 10/12 cats positive, respectively). Antibody testing with Witness and Anigen Rapid was also positive in a high proportion of cats 2 weeks after the second primary FIV vaccination (8/12 and 7/12, respectively), but antibody levels declined below the level of detection in most cats (10/12) by 1 month after the third (final) primary FIV vaccination. All cats tested negative using Witness and Anigen Rapid 6 months after the third primary FIV vaccination. Conclusions and relevance This study has shown that a primary course of FIV vaccination does not interfere with FIV antibody testing in cats using Witness and Anigen Rapid, provided primary vaccination has not occurred within the previous 6 months. Consequently, Witness and Anigen Rapid antibody test kits can be used reliably to determine FIV infection status at the time of annual booster FIV vaccination to help detect 'vaccine breakthroughs' and in cats that have not received a primary course of FIV vaccination within the preceding 6 months. The duration of antibody response following annual booster FIV vaccination and the resulting effect on antibody testing using PoC kits needs to be determined by further research. The mechanism(s) for the variation in FIV antibody test kit performance remains unclear.


Static posturography and intravenous alcohol.
Twelve health subjects were assessed using static posturography before and after intravenous alcohol infusion in a double-blind experiment. The dose was 0.5 g ethanol per kg body weight in 15 minutes, which raised the blood alcohol concentration to a level of approximately 1 mg/mL. Among other parameters, the average body sway velocity (BSV) and area of body sway (BSA) were measured. BSV was the most sensitive parameter for detecting increased body sway after alcohol infusion, and a significant effect of alcohol on its values was seen at 0.46 to 1.0 mg/mL alcohol concentrations. The second best indicator was the BSA. There was a positive correlation between the BSV and the BSA. The other parameters were not affected. The Romberg quotient remained constant during the alcohol test. The test battery used was relevant to distinguish the effect of alcohol on balance. In this study, acute blood alcohol concentrations of around 0.5 to 1.0 mg/mL affected BSV more significantly than BSA. The authors do not, however, recommend the test for forensic purposes in examining drivers with alcohol in their blood, as there is too much interindividual dispersion in the results.


Atrial parasystole.
A case of the relatively rare atrial parasystole is reported, and this interesting cardiac arrhythmia is reviewed. Atypical deviations from classical parasystole are reviewed, and modern concepts of parasystole as they differ from traditional, classical parasystole are addressed.


[What is appropriate care for women who smoke during pregnancy?].
There are few publications on smoking biomarkers in pregnant woman, but nothing suggests that their contribution differs during pregnancy. Many publications have examined the predictive value of the biomarkers of smoking, but the comparative value is not clear. To our knowledge no study has used biomarkers of the smoking to monitor smoking cessation during pregnancy. Blood nicotine is not retained as a useful biomarker. Most authors retain urinary cotinine as the gold standard. There is no consensus on measurement techniques. Cotinine can be measured in blood, saliva and in cord blood. Active and passive smoking can be monitored with urinary cotinine. Rapid strip tests provide useful results to differentiate smokers from non-smokers, but not to quantify nicotinic intoxication. All published papers have been supported by the firm marketing the strip. There have been few studies in pregnant woman on expired CO rate, but the method is validated. Measurement of thiocyanates and other biomarkers does not currently provide useful information for routine surveillance of pregnant smoking women.


Preanesthetic medication with rectal midazolam in children undergoing dental extractions.
Three different dosages (0.25, 0.35, and 0.45 mg/kg) of rectally administered midazolam were compared with each other and with placebo for preanesthetic medication in children undergoing dental extractions. Eighty patients between the ages of 2 and 10 years were randomly allocated into four groups in this double-blind study. The results from this trial show that 30 minutes after rectal administration of all doses of midazolam, good anxiolysis, sedation, and cooperation were obtained in most patients. A high prevalence (23%) of disinhibition reactions was observed, particularly in the 0.45 mg/kg group. For this reason, 0.25 or 0.35 mg/kg appears to be the dose of choice when rectal midazolam is used for premedication in children.


A "Double-Diamond Superlattice" Built Up of Cd17S4(SCH2CH2OH)26 Clusters.
A simple preparation of Cd(17)S(4)(SCH(2)CH(2)OH)(26) clusters in aqueous solution leads to the formation of colorless blocky crystals. X-ray structure determinations revealed a superlattice framework built up of covalently linked clusters. This superlattice is best described as two enlarged and interlaced diamond or zinc blende lattices. Because both the superlattice and the clusters display the same structural features, the crystal structure resembles the self-similarities known from fractal geometry. The optical spectrum of the cluster solution displays a sharp transition around 290 nanometers with a large absorption coefficient ( approximately 84,000 per molar per centimeter).


Validation of a high-performance liquid chromatographic method for the simultaneous determination of tramadol and its impurities in oral drops as a pharmaceutical formulation.
The novel, rapid high performance liquid chromatographic method for the determination of tramadol hydrochloride and its three impurities was developed and validated. The method can simultaneously assay potassium sorbate, used as preservative, and saccharin sodium, used as sweetener in tramadol pharmaceutical formulation. The separation was carried out on a C(18) XTerra (150 mm x 4.6 mm, 5 mm) column using acetonitrile-0.015 M Na(2)HPO(4) buffer (2:8, v/v) as mobile phase (pH value 3.0 was adjusted with orthophosphoric acid) at a flow rate 1.0 ml min(-1), temperature of the column 20 degrees C and UV detection at 218 nm. The method was found to be linear (r > 0.999) in the range of 0.05-0.8 mg ml(-1) for tramadol hydrochloride, 0.1-1.2 mg ml(-1) for impurities B and C and for impurity A (r > 0.995) in the range 0.15-2.4 mg ml(-1). The low RSD values indicate good precision and high recovery values indicate excellent accuracy of the HPLC method. Developed method was successfully applied to the determination of tramadol hydrochloride, its investigated impurities and potassium sorbate in commercial formulation. The recovery of tramadol hydrochloride was 98.25% and RSD was 1.80%. The method is rapid and sensitive enough to be used to analyse Trodon oral drops.


Microsurgical TESE and the distribution of spermatogenesis in non-obstructive azoospermia.
We wished to map the distribution of spermatogenesis in different regions of the testis in 58 men with non-obstructive azoospermia, and to develop a rational microsurgical strategy for the testicular sperm extraction (TESE) procedure. One goal was to maximize the chances for retrieving spermatozoa from such men, to minimize tissue loss and pain, and to preserve the chance for successful future procedures. Another goal was to expand upon the previously reported quantitative histological analysis of testicular tissue in 45 azoospermic men undergoing conventional TESE, this time using microsurgical as well as histological mapping. Tubular fullness observed at microsurgery and the presence of spermatozoa in the TESE specimen was compared with the quantitative histological analysis of spermatogenesis. Thus, our conclusions about the distribution of spermatogenesis are based on our experience with TESE in 103 consecutive cases of non-obstructive azoospermia. It was confirmed that men with non-obstructive azoospermia caused by germinal failure have a mean of 0 to 3 mature spermatids per seminiferous tubule in contrast to 17-35 mature spermatids per tubule in men with normal spermatogenesis and obstructive azoospermia. The former represented the threshold of quantitative spermatogenesis which must be exceeded in order for spermatozoa to 'spill over' into the ejaculate. Both testicular 'mapping' by multiple biopsy (n = 15) and microsurgical removal of contiguous strips of testicular tissue (n = 43) revealed a diffuse, rather than regional, quantitative distribution of spermatogenesis. A microsurgical approach resulted in the minimal amount of tissue loss and minimal-to-no pain (compared with the original 45 cases already reported). By this means it is often possible to immediately locate the few tubules with spermatogenesis at microsurgery, under local anaesthesia. But even in cases where greater amounts of tissue must be removed in order to find spermatozoa, the microsurgical TESE procedure prevents secondary testicular damage by protecting blood supply and preventing pain and atrophy from increased testicular pressure. Thus, future attempts at TESE-ICSI need not be compromised.


Ethnobotanical survey of knowledge and usage custom of traditional insect/mosquito repellent plants among the Ethiopian Oromo ethnic group.
Repellent plants usage is an integral part of Ethiopian tradition and has been practiced over many centuries. Hence, the aim of this study was to assess the knowledge and usage custom of traditional insect/mosquito repellent plants among the Oromo ethnic group in Ethiopia. The ethnobotanical survey was conducted between January and March 2009. All 276 household members were interviewed on knowledge and usage custom of traditional repellent plants, using a pre-tested questionnaire in Kofe kebele, Jimma zone, Ethiopia. 83.6% respondents had adequate knowledge and usage custom regarding insect/mosquito repellent plants. Application of smoke by burning the repellent plant materials was the most common practice. The chi-square test result revealed that there was no statistically significant association found between the knowledge about insect repellent plants and sex (p-value=0.8912), educational status (p-value=0.7504), and age (p-value=0.1631) of the respondents. However, usage custom of repellent plants was significantly associated with sex (p-value=0.0002) and average monthly income (p-value=0.0001) although not with educational status (p-value=0.5206) of the respondents. Repellent efficacy of these plants is undetermined and therefore the scientific validity should be evaluated by conducting further laboratory and field research. Majority of the repellent plants have been used as medicine to treat various ailments by the local community. Furthermore, they are easily available, accessible and affordable therefore usage of traditional repellent plants should be promoted among the local residents in order to reduce vector-borne disease prevalence.


Conformational changes of recombinant monoclonal antibodies by limited proteolytic digestion, stable isotope labeling, and liquid chromatography-mass spectrometry.
Limited proteolytic digestion is a method with a long history that has been used to study protein domain structures and conformational changes. A method of combining limited proteolytic digestion, stable isotope labeling, and mass spectrometry was established in the current study to investigate protein conformational changes. Recombinant monoclonal antibodies with or without the conserved oligosaccharides, and with or without oxidation of the conserved methionine residues, were used to test the newly proposed method. All of the samples were digested in ammonium bicarbonate buffer prepared in normal water. The oxidized deglycosylated sample was also digested in ammonium bicarbonate buffer prepared in (18)O-labeled water. The sample from the digestion in (18)O-water was spiked into each sample digested in normal water. Each mixed sample was subsequently analyzed by liquid chromatography-mass spectrometry (LC-MS). The molecular weight differences between the peptides digested in normal water versus (18)O-water were used to differentiate peaks from the samples. The relative peak intensities of peptides with or without the C-terminal incorporation of (18)O atoms were used to determine susceptibility of different samples to trypsin and chymotrypsin. The results demonstrated that the method was capable of detecting local conformational changes of the recombinant monoclonal antibodies caused by deglycosylation and oxidation.


Effect of folic acid and antioxidant vitamins on endothelial dysfunction in patients with coronary artery disease.
The purpose of this study was to determine whether lowering homocysteine levels with folic acid, with or without antioxidants, will improve endothelial dysfunction in patients with coronary artery disease (CAD). Elevated plasma homocysteine levels are a risk factor for atherosclerosis. Homocysteine may promote atherogenesis through endothelial dysfunction and oxidative stress. In a double-blind, placebo-controlled, randomized trial, we used vascular ultrasound to assess the effect of folic acid alone or with antioxidants on brachial artery endothelium-dependent flow-mediated dilation (FMD). Seventy-five patients with CAD (screening homocysteine level > or =9 micromol/liter) were randomized equally to one of three groups: placebo, folic acid alone or folic acid plus antioxidant vitamins C and E. Patients were treated for four months. Plasma folate, homocysteine, FMD and nitroglycerin-mediated dilation were measured before and after four months of treatment. Plasma folate, homocysteine and FMD were unchanged in the placebo group. Compared with placebo, folic acid alone increased plasma folate by 475% (p < 0.001), reduced plasma homocysteine by 11% (p = 0.23) and significantly improved FMD from 3.2 +/- 3.6% to 5.2 +/- 3.9% (p = 0.04). The improvement in FMD correlated with the reduction in homocysteine (r = 0.5, p = 0.01). Folic acid plus antioxidants increased plasma folate by 438% (p < 0.001), reduced plasma homocysteine by 9% (p = 0.56) and insignificantly improved FMD from 2.6 +/- 2.4% to 4.0 +/- 3.7% (p = 0.45), as compared with placebo. Nitroglycerin-mediated dilation did not change significantly in any group. Folic acid supplementation significantly improved endothelial dysfunction in patients with coronary atherosclerosis. Further clinical trials are required to determine whether folic acid supplementation may reduce cardiovascular events.


Granulomatous cryptococcal prostatitis diagnosed by transrectal biopsy.
Cryptococcal infection primarily involves the lung and is hematogenously spread to other organs. Sometimes it might affect the genitourinary tract, and rare cases have been reported involving the prostate without systemic infection. We report a case of granulomatous prostatitis as a result of Cryptococcus neoformans yeast in an immunocompromised patient with alcoholic liver cirrhosis, which was diagnosed by transrectal ultrasound guided biopsy and treated with antifungal medication.


Epidemiology of Kaposi's sarcoma in Sweden prior to the acquired immunodeficiency syndrome.
We studied retrospectively 529 cases of Kaposi's sarcoma (KS) reported to the Swedish Cancer Registry between 1958 and 1982 to determine incidence rates, survival and rate ratios, together with the frequency and types of associated malignancies. The age-standardized (Swedish population 1970) incidence rate generally increased over the time period, with a mean of 0.27 cases per 100,000 population per year (males 0.40, females 0.14). The incidence rate ratio (based on 5-year intervals and relative to the earliest period) reached 2.06 for males and 3.76 for females in the 1968-1972 interval, while the actual peak occurred between 1971 and 1974 for both sexes. Poisson regression modelling suggested a transient shift in the age-specific male incidence rate pattern with a relative increase of the disease in younger age groups (p = 0.05) up to 1968-1972. The age-adjusted male:female ratio did not change significantly from 2.9 during the period of study. In relation to the general population, 18% fewer men and 24% fewer women were alive 10 years after the diagnosis had been made. Ninety-nine (19%) cases had other primaries, of which 17 were neoplasms of lymphocytic origin. Lymphoproliferative malignancy was 2.5 times (95% CI 1.38, 4.37) more common than expected in patients with KS (in particular in females) but a definite increase in other malignancies was not apparent. It is questionable whether immune dysfunction due to other malignant disease or drug therapy can account for the epidemiologic changes in KS, which began almost 2 decades prior to the AIDS epidemic in Sweden.


Chloride-inducible transient apoplastic alkalinizations induce stomata closure by controlling abscisic acid distribution between leaf apoplast and guard cells in salt-stressed Vicia faba.
Chloride stress causes the leaf apoplast transiently to alkalize, an event that is presumed to contribute to the ability of plants to adapt to saline conditions. However, the initiation of coordinated processes downstream of the alkalinization is unknown. We hypothesize that chloride-inducible pH dynamics are a key chemical feature modulating the compartmental distribution of abscisic acid (ABA) and, as a consequence, affecting stomata aperture. Apoplastic pH and stomata aperture dynamics in intact Vicia faba leaves were monitored by microscopy-based ratio imaging and porometric measurements of stomatal conductance. ABA concentrations in leaf apoplast and guard cells were compared with pH dynamics by gas-chromatography-mass-spectrometry (GC-MS) and liquid-chromatography-tandem-mass spectrometry (LC-MS/MS). Results demonstrate that, upon chloride addition to roots, an alkalizing factor that initiates the pH dynamic propagates from root to leaf in a way similar to xylem-distributed water. In leaves, it induces a systemic transient apoplastic alkalinization that causes apoplastic ABA concentration to increase, followed by an elevation of endogenous guard cell ABA. We conclude that the transient alkalinization, which is a remote effect of chloride stress, modulates the compartmental distribution of ABA between the leaf apoplast and the guard cells and, in this way, is instrumental in inducing stomata closure during the beginning of salinity.


Korteweg-de Vries equation and energy sharing in Fermi-Pasta-Ulam.
We address the problem of equipartition in a long Fermi-Pasta-Ulam (FPU) chain. After giving a precise relation between FPU and Korteweg-de Vries we use the latter equation to show that, corresponding to initial data a la Fermi, the time average of the energy on the kth mode decreases exponentially with kN. The result persists in the thermodynamic limit.


Use of antihypertensive drugs by Medicare enrollees: does type of drug coverage matter?
Research has demonstrated that Medicare beneficiaries with drug coverage consume more clinically essential drugs. However, generosity of coverage varies considerably across beneficiaries. This study examines the association between types of drug coverage and the consumption and cost per tablet of essential antihypertensive medications among beneficiaries with hypertension. The findings indicate that while both state- and employer-sponsored drug coverage are associated with greater consumption of antihypertensive drugs and lower out-of-pocket costs per tablet, private supplemental coverage is not associated with greater use and is associated with only slightly lower out-of-pocket costs than among noncovered beneficiaries.


Typological prediction of response to amitriptyline: a replication study.
This paper reports a replication study of prediction of outcome by a cluster-analysis derived four-group typoloy of depression. 143 acutely depressed women were treated with amitriptyline for 4 weeks. In replication of the earlier findings, anxious depressives showed the worst response, hostile depressives and young depressive with personality disorder the best, with psychotic depressive intermediate. The findings provide further validating evidence for the typology, and for the view that nonpsychotic depressives are heterogenous.


ICU patients' recall of emotional reactions in the trajectory from falling critically ill to hospital discharge: follow-ups after 3 and 12 months.
Patients' memories of frightening ICU experiences may be a threat to later psychological recovery. The purpose of the study is to describe ICU patients' recall of their emotional reactions, from falling critically ill to hospital discharge; this at 3 and 12 months following discharge from the ICU. The study is qualitative and concerns eight ICU patients ventilated for more than 72h. The participants were interviewed twice and the data were subjected to qualitative content analysis. It emerged that the memories of emotions during the trajectory of critical illness were extensive, detailed and strong, and that unpleasant emotions were clearly stable over time. At 12 months as compared with 3 months, the unpleasant emotions were less intense and had less prominent; furthermore the ICU care was more greatly associated with a sense of security, and there was greater recall of caring doctors and nurses (though not of their names) as well as next of kin. The study generated knowledge not previously described about how ICU patients' recollection of their emotions during the trajectory of critical illness changes over time. This has implications regarding future study of patients' ICU memories and regarding patients' need for support in coping with such memories.


Liver transplantation in Jehovah's witnesses.
For religious reasons, Jehovah's witnesses refuse transfusion of blood products (red cells, platelets, plasma), but may accept organ transplantation. The authors developed a multidisciplinary protocol for liver transplantation in Jehovah's witnesses. In a 6-year period, nine Jehovah's witness patients were listed for liver transplantation. They received preoperative erythropoietin therapy, with iron and folic acid that allowed significant haematocrit increase. Two patients underwent partial spleen embolization to increase platelet count. Seven patients underwent cadaveric whole liver transplantation, and two right lobe living-related liver transplantation, using continuous circuit cell saving system and high dose aprotinin. No patient received any blood product during the surgical procedure. One patient suffering from deep anaemia after living-related liver transplantation was transfused as required by his family, but died from aspergillus infection. One 6-year-old child was transfused against her parent's will. The authors demonstrated that it is possible to increase haematocrit and platelet levels in cirrhotic patients awaiting liver transplantation. They were able to reduce intraoperative need for blood products, allowing liver transplantation in prepared Jehovah's witness patients. This experience may be beneficial for non-Jehovah's witness liver transplant recipients.


Greater cell cycle inhibition and cytotoxicity induced by 2-deoxy-D-glucose in tumor cells treated under hypoxic vs aerobic conditions.
In order to investigate the hypothesis that cells found in hypoxic areas of solid tumors are more sensitive to glycolytic inhibitors than cells growing aerobically, we have previously characterized three distinct in vitro models (A, B and C) that simulate this condition. In all of the models it was shown that cells growing under hypoxic conditions are hypersensitive to the glycolytic inhibitor 2-deoxy- d-glucose (2-DG). However, in those studies cytostatic and cytotoxic effects were not distinguished from one another. Since successful treatment of cancer includes not only slowing down but also actually killing tumor cells, studies were undertaken to assess the effects of 2-DG on cell cycle progression and cell death. Using flow cytometry and cell viability assays, it was found that 2-DG caused significantly greater cell cycle inhibition and cell death in all three hypoxic models as compared to aerobically growing control cells. In model A (a chemically induced model of hypoxia in which rhodamine-123 is used to block oxidative phosphorylation), 1200 microg/ml of 2-DG was shown to induce more cell cycle arrest in late S/G(2) and more cell death than in the aerobic cell counterpart treated with 3600 microg/ml 2-DG. In rho(0) cells which are genetically constructed to be unable to perform oxidative phosphorylation (model B), an even greater window of selectivity (more than tenfold) between hypoxic and aerobic cells was found when considering 2-DG's effects on cell cycle arrest and cell death. In the environmental model (model C), where cells were grown under reduced amounts of external oxygen (0.1%), hypersensitivity to the effects of 2-DG with respect to cell cycle arrest and cell death were also observed. Overall, these results indicate that cells growing under anaerobic conditions respond with greater sensitivity to the effects of 2-DG on cell cycle inhibition and cell death than those growing under aerobic conditions. This supports our contention that glycolytic inhibitors added to standard chemotherapeutic protocols should increase treatment efficacy by selectively killing the slow-growing cells, which are found in the hypoxic portions of solid tumors, while sparing most of the normal cells that are also slow-growing but are living under aerobic conditions.


Allorecognition in compound ascidians.
In botryllids (colonial ascidians), there are two types of allorecognition: colony specificity and colony resorption. Colony specificity is manifested by fusion and rejection between two conspecific colonies. The genetic basis for this colony specificity resides in a single highly polymorphic gene locus (fusibility locus) with codominantly expressed alleles. Two colonies with no alleles in common at this locus reject each other, whereas colonies sharing at least one allele at the fusibility locus fuse and form a chimera. That is, in colony specificity, self components are distinguished from nonself components, and failure to recognize self induces rapid rejection reactions. The process of rejection in colony specificity is not uniform among all botryllid ascidians. Colony resorption can occur after the establishment of fusion between two colonies. Zooids of one partner of a chimera are resorbed more than 1 week after fusion, or, by amputation of fused blood vessels, the chimera becomes separated into the two original colonies. Colony resorption is also controlled mainly by the fusibility locus. It usually occurs in a chimera between two colonies sharing only one allele at this locus. In colony resorption, nonself determinants are recognized and chronic rejection reactions are induced resembling MHC-dependent graft rejection. Based on these findings, the fusibility locus of botryllids seems to be very similar to the MHC of vertebrates. Considering that vertebrates evolved directly from ascidians, it is likely that the fusibility locus is an ancestral form of the vertebrate MHC.


Prevalence of hypovitaminosis D and associated factors in adolescent students of a capital of northeastern Brazil.
Hypovitaminosis D is a frequent problem in the world and can be influenced by several factors. To estimate the prevalence of hypovitaminosis D and associated factors in adolescent students of a capital city of northeastern Brazil. Cross-sectional epidemiological study assessing 220 school adolescents of both sexes aged 15 to 19 years. A questionnaire was applied to assess sociodemographic (skin color, mother's education and receiving social benefits) and behavioral data (number of hours of sleep per day, sun exposure, physical activity and dietary vitamin D intake). Anthropometric nutritional status was assessed by BMI (body mass index) for age. Serum 25 (OH) D concentrations, PTH and serum calcium were measured by blood samples. We identified individuals with hypovitaminosis D as those with 25 (OH) D < 30 ng/dL. The analysis of factors associated with hypovitaminosis D was performed by simple and multivariate Poisson Regression. The prevalence of hypovitaminosis D was 57.3%. The female population had a significantly higher prevalence than the male. In the final adjusted model, the variable independently associated with hypovitaminosis D in females was the lowest serum calcium concentrations, and for males it was BMI, in which adolescents who had overweight/obesity were 2.4 times more likely to have hypovitaminosis D than the eutrophic ones. The present study found a high prevalence of hypovitaminosis D in the analyzed population, especially in female adolescents. In addition, the factors independently associated with hypovitaminosis D were found to be overweight/obese in boys and low calcium concentrations in girls.


Ex vivo whole-embryo culture of caspase-8-deficient embryos normalize their aberrant phenotypes in the developing neural tube and heart.
Caspase-8 plays the role of initiator in the caspase cascade and is a key molecule in death receptor-induced apoptotic pathways. To investigate the physiological roles of caspase-8 in vivo, we have generated caspase-8-deficient mice by gene targeting. The first signs of abnormality in homozygous mutant embryos were observed in extraembryonic tissue, the yolk sac. By embryonic day (E) 10.5, the yolk sac vasculature had begun to form inappropriately, and subsequently the mutant embryos displayed a variety of defects in the developing heart and neural tube. As a result, all mutant embryos died at E11.5. Importantly, homozygous mutant neural and heart defects were rescued by ex vivo whole-embryo culture during E10.5-E11.5, suggesting that these defects are most likely secondary to a lack of physiological caspase-8 activity. Taken together, these results suggest that caspase-8 is indispensable for embryonic development.


[Participation of cyclic nucleotides in immunogenesis and immune reactions of lymphocytes].
The paper deals with generalized literary and author's own data testifying to the role of cyclic nucleotides as mediators in the effect of specific and nonspecific factors on immunogenesis, from the proliferation of stem hemopoietic cell of bone marrow to the reaction of T and B lymphocytes to antigens. It is shown that changes in the system of lymphocytes cyclic nucleotides are most probably secondary in response to changes in intracellular concentration and distribution of calcium ions. Certain evidence is presented on immunopharmacological preparations based on cyclic nucleotides, their analogs and preparations modulating the activity of phosphodiesterases.


Quantitative determination of activated coagulation factor XI as an impurity in therapeutic immunoglobulins from Chinese blood fractionation companies.
Residual activated coagulation factor XI (FXIa) has been suggested to play an important role in thromboembolic events associated with the use of intravenous immunoglobulin (IVIG) lots. This study investigated the predominant plasma proteases in 42 IVIG lots from 4 Chinese manufacturers. In one-stage clotting assays, the procoagulant activities of factors II, VII, IX, X, XI, and XII were quantified. Non-activated partial thromboplastin time and a modified thrombin generation test served as global and FXIa-specific clotting assays, respectively. We found that coagulation factor clotting activities of the 42 IVIG lots were below the detection limit of the assays, except for the products of manufacturer B (lots of 2010), in which 0.030 to 0.032 IU/mL FXI:C were detected. The peak time of thrombin using a thrombin generation test was greater than 35 min, the relevant amount of FXIa was below 0.37 nM, and non-activated partial thromboplastin time was greater than 200 s. Consequently, the 42 IVIG lots showed non-significant procoagulant potential. Further study is required to determine whether a program for FXIa determination in IVIG products should be launched in China.


Functional Magnetic Resonance Imaging to Assess the Neurobehavioral Impact of Dysphotopsia with Multifocal Intraocular Lenses.
To investigate the association between dysphotopsia and neural responses in visual and higher-level cortical regions in patients who recently received multifocal intraocular lens (IOL) implants. Cross-sectional study. Thirty patients 3 to 4 weeks after bilateral cataract surgery with diffractive IOL implantation and 15 age- and gender-matched control subjects. Functional magnetic resonance imaging (fMRI) was performed when participants viewed low-contrast grating stimuli. A light source surrounded the stimuli in half of the runs to induce disability glare. Visual acuity, wavefront analysis, Quality of Vision (QoV) questionnaire, and psychophysical assessment were performed. Cortical activity (blood oxygen level dependent [BOLD] signal) in the primary visual cortex and in higher-level brain areas, including the attention network. When viewing low-contrast stimuli under glare, patients showed significant activation of the effort-related attention network in the early postoperative period, involving the frontal, middle frontal, parietal frontal, and postcentral gyrus (multisubject random-effects general linear model (GLM), P < 0.03). In contrast, controls showed only relative deactivation (due to lower visibility) of visual areas (occipital lobe and middle occipital gyrus, P < 0.03). Patients also had relatively stronger recruitment of cortical areas involved in learning (anterior cingulate gyrus), task planning, and solving (caudate body). Patients reporting greater symptoms induced by dysphotic symptoms showed significantly increased activity in several regions in frontoparietal circuits, as well as cingulate gyrus and caudate nucleus (q < 0.05). We found no correlation between QoV questionnaire scores and optical properties (total and higher order aberration, modulation transfer function, and Strehl ratio). This study shows the association between patient-reported subjective difficulties and fMRI outcomes, independent of optical parameters and psychophysical performance. The increased activity of cortical areas dedicated to attention (frontoparietal circuits), to learning and cognitive control (cingulate), and to task goals (caudate) likely represents the beginning of the neuroadaptation process to multifocal IOLs.


Curcumin molecular targets in obesity and obesity-related cancers.
Obesity is characterized as an increased BMI, which is associated with the increased risk of several common cancers, including colorectal, breast, endometrial, renal, esophageal, gallbladder, melanoma, multiple myeloma, leukemia, lymphoma and prostate cancer. The increased risk of obesity-related cancers could be mediated by insulin resistance, adipokines, obesity-related inflammatory cytokines, sex hormones, transcription factors and oxidative stress, which disrupt the balance between cell proliferation and apoptosis. The yellowish compound, curcumin (diferuloylmethane), is known to possess multifaceted pharmacological effects. The molecular mechanisms linking obesity to cancer risk, and how curcumin mediates anticancer and obesity activities, have not yet been publicized. Curcumin modulates multiple molecular targets and reverses insulin resistance as well as other symptoms that are associated with obesity-related cancers. In this study, we show that ample evidence exists to support recommendations that curcumin mediates multiple molecular pathways, and is considered to be of therapeutic value in the treatment and prevention of obesity-related cancers.


Artificial intelligence-guided tissue analysis combined with immune infiltrate assessment predicts stage III colon cancer outcomes in PETACC08 study.
Diagnostic tests, such as Immunoscore, predict prognosis in patients with colon cancer. However, additional prognostic markers could be detected on pathological slides using artificial intelligence tools. We have developed a software to detect colon tumour, healthy mucosa, stroma and immune cells on CD3 and CD8 stained slides. The lymphocyte density and surface area were quantified automatically in the tumour core (TC) and invasive margin (IM). Using a LASSO algorithm, DGMate (DiGital tuMor pArameTErs), we detected digital parameters within the tumour cells related to patient outcomes. Within the dataset of 1018 patients, we observed that a poorer relapse-free survival (RFS) was associated with high IM stromal area (HR 5.65; 95% CI 2.34 to 13.67; p<0.0001) and high DGMate (HR 2.72; 95% CI 1.92 to 3.85; p<0.001). Higher CD3+ TC, CD3+ IM and CD8+ TC densities were significantly associated with a longer RFS. Analysis of variance showed that CD3+ TC yielded a similar prognostic value to the classical CD3/CD8 Immunoscore (p=0.44). A combination of the IM stromal area, DGMate and CD3, designated 'DGMuneS', outperformed Immunoscore when used in estimating patients' prognosis (C-index=0.601 vs 0.578, p=0.04) and was independently associated with patient outcomes following Cox multivariate analysis. A predictive nomogram based on DGMuneS and clinical variables identified a group of patients with less than 10% relapse risk and another group with a 50% relapse risk. These findings suggest that artificial intelligence can potentially improve patient care by assisting pathologists in better defining stage III colon cancer patients' prognosis.


Recognition of the ligand-type specificity of classical and non-classical MHC I proteins.
Functional characterization of proteins belonging to the MHC I superfamily involves knowing their cognate ligands, which can be peptides, lipids or none. However, the experimental identification of these ligands is not an easy task and generally requires some a priori knowledge of their chemical nature (ligand-type specificity). Here, we trained k-nearest neighbor and support vector machine classifiers that predict the ligand-type specificity MHC I proteins with great accuracy. Moreover, we applied these classifiers to human and mouse MHC I proteins of uncharacterized ligands, obtaining some results that can be instrumental to unravel the function of these proteins.


Low self-efficacy is a risk factor for depression among male Japanese workers: a cohort study.
The identification of risk factors for depression is necessary for the primary prevention of depression. The aim of this study is to determine whether self-efficacy (SE) is associated with onset of depression among workers. Medical expenditure records of 1,803 workers, who were clerks, system engineers, researchers, and service and sales workers in a software development company, were analyzed. Gender, age, job post, marital status, working hours, and SE were measured at baseline. Participants were divided according to quartiles of SE points. Risk ratios for undergoing a medical consultation due to depression were calculated using a multivariable Cox proportional hazards model. Of the 1,803 participants, 58 underwent medical consultation due to depression during a mean of 1.8 years of follow-up. Compared with the lowest quartile (Q1) of SE, adjusted hazard ratios (HR) were 0.65 (95%CI 0.34-1.25) for Q2, 0.49 (0.24-1.00) for Q3, and 0.40 (0.18-0.88) for Q4. In men, adjusted HRs were 0.87 (0.41-1.86) for Q2, 0.61 (0.26-1.41) for Q3, and 0.37 (0.14-0.98) for Q4. In women, no significant association was found. The present study suggests that low SE is a risk factor for onset of depression among male Japanese workers.


Studies of complement autoactivatability in hereditary angioedema: direct relationship to functional C-1-INA and the effect of classical pathway activators.
It has been observed earlier that the hemolytic complement in diluted sera obtained from patients with hereditary angioedema (HAE) undergoes spontaneous decay when incubated at 37 degrees C. Employing individual serum from patients at different stages of this disease it was demonstrated that this spontaneous loss of hemolytic complement also occurs without dilution and is directly linked to the absence of functional C-1-INA. Incubation of HAE serum resulted in a loss of activity which appears to be dependent upon the concentration of functional C-1-INA. While C-1-INA levels less than 50 micrograms/ml lead to rapid depletion with time, reconstitution of deficient sera with highly purified C-1-INA or of undiluted NHS inhibited spontaneous activation. Furthermore, NHS was rendered susceptible to autoactivation when its C-1-INA was depleted by passage over an anti-C-1-INA Sepharose 4B affinity column in the presence of 10 mM EDTA, indicating that in the absence of functional C-1-INA, C1 undergoes an uninhibited spontaneous autoactivation which leads to the consumption of C4 and C2 but not C3. Consumption of C3 was observed, however, in HAE sera that contained a significant amount of immune complexes. Incubation of HAE sera with highly purified Hageman factor fragment (5 micrograms/ml), or aggregated IgG (2 mg/ml) was found to accelerate the rate of decay when compared to untreated samples while sera from patients under treatment with Danazol or Stanozolol failed to autoactive. These results suggest that, the absence of C-1-INA, may, by itself trigger the dissociation and autoactivation of C1 in the sera of such patients; however, the presence of other complement activators accelerates the reaction. This inherent property of HAE sera, i.e., spontaneous autoactivation at 37 degrees C, may be a useful screening test but direct determination of C-1-INA activity is required to establish the precise diagnosis.


Hypoxia: jump-starting inflammation.
Tissue hypoxia affects immunity and inflammation; however, the way in which changes in oxygen levels may modulate dendritic cell (DC) function is still not clear. Bosco et al report the gene expression profiling of hypoxic mature DCs and identify TREM-1 as a novel hypoxia-inducible gene that may amplify inflammatory responses.


Making research integral to home care services.
Home care is the fastest growing segment of the Canadian healthcare system, yet research on patient safety has been conducted predominantly in institutional settings. This is a case example of how Victorian Order of Nurses Canada, a national not-for-profit home and community care provider, embedded a nurse researcher to create an environment in which health services research flourished. This model strategically propelled important issues such as home care safety on to the national research and policy agendas and helped leverage change in multiple levels of the healthcare system. This is a call to action for building partnerships to have a researcher as an integral team member in organizations providing home care services.


Color-coded duplex endoscopic ultrasound of the adrenals.
Imaging of the adrenals by endoscopic ultrasound (EUS) is a valuable technique for detection and localization of adrenal lesions, but endosonomorphological tumor distinction remains difficult. In this single-center study, the amount of blood flow in common adrenal lesions, such as adrenal adenomas, adrenal hyperplasia, and pheochromocytomas, was visualized by color-coded duplex EUS (CD-EUS) and was retrospectively analysed. Therefore, we reviewed our EUS database to evaluate and correlate the perfusion patterns of common adrenal lesions with histologically confirmed diagnosis, possible malignancy, and endosonomorphological features such as echogeneity, echostructure, and tumor size. CD-EUS was performed using an endosonoscope Pentax FG 32 UA with a longitudinal 7.5 MHz sector array and Hitachi EUB 525 ultrasound system. In 38 consecutive patients (male=19; female=19; age: mean 53+/-16 yr SD), perfusion patterns of 46 histologically confirmed adrenal, para- or extra-adrenal lesions of adrenal origin (adenoma: no.=20; nodular hyperplasia: no.=11; pheochromocytoma: no.=15; diameter 26+/-15 mm, range 6-70 mm) were analyzed and classified semiquantitatively as "not" (no.=24), "slightly" (no.=12), "moderately" (no.=4) or "highly" (no.=6) hypervascularized. Compared to adenomas (p=0.003) and nodular hyperplasia (p=0.047), pheochromocytomas showed a significantly higher grade of perfusion. There was no relationship between perfusion patterns and localization of pheochromocytomas (adrenal: 8; paraadrenal: 3; extra-adrenal: 4). Vascularization was not statistically associated with tumor echogeneity, echostructure, malignancy or tumor size. CD-EUS is an additional tool for adrenal endosonographic tumor distinction and seems to improve the endosonographic detection of pheochromocytomas by visualization of hypervascularization. As an overlap of perfusion patterns exists, CD-EUS findings must be interpreted in the context of clinical, laboratory and chemical results.


Dermoscopy for the family physician.
Noninvasive in vivo imaging techniques have become an important diagnostic aid for skin cancer detection. Dermoscopy, also known as dermatoscopy, epiluminescence microscopy, incident light microscopy, or skin surface microscopy, has been shown to increase the clinician's diagnostic accuracy when evaluating cutaneous neoplasms. A handheld instrument called a dermatoscope or dermoscope, which has a transilluminating light source and standard magnifying optics, is used to perform dermoscopy. The dermatoscope facilitates the visualization of subsurface skin structures that are not visible to the unaided eye. The main purpose for using dermoscopy is to help correctly identify lesions that have a high likelihood of being malignant (i.e., melanoma or basal cell carcinoma) and to assist in differentiating them from benign lesions clinically mimicking these cancers. Colors and structures visible with dermoscopy are required for generating a correct diagnosis. Routinely using dermoscopy and recognizing the presence of atypical pigment network, blue-white color, and dermoscopic asymmetry will likely improve the observer's sensitivity for detecting pigmented basal cell carcinoma and melanoma. A two-step algorithm based on a seven-level criterion ladder is the foundation for dermoscopic evaluation of skin lesions. The first step of the algorithm is intended to help physicians differentiate melanocytic lesions from the following nonmelanocytic lesions: dermatofibroma, basal cell carcinoma, seborrheic keratosis, and hemangioma. The second step is intended to help physicians differentiate nevi from melanoma using one of several scoring systems. From a management perspective, the two-step algorithm is intended to guide the decision-making process on whether to perform a biopsy, or to refer or reassure the patient.


[Significance of lacrimal fluid peroxidation and anti-radical defense parameters for prediction and treatment of complicated myopia].
Study of lipid peroxidation and antiradical defense parameters in the lacrimal fluid from 270 eyes of children and adolescents with progressive myopia demonstrated a relationship between the development of peripheral vitreochorioretinal dystrophies and imbalance between antioxidant activity (AOA) of lacrimal fluid and intensity of radical formation evaluated by chemiluminescence (CL) intensity. The AOA/CL ratio is proposed as a reliable indicator for predicting the course of progressive myopia. A value < 30 indicates poor level of antioxidant defense of ocular media and tissues and is a prognostically unfavorable sign as regards development of peripheral vitreochorioretinal dystrophy. A local antioxidant remedy has been developed and clinically tried for preventing and treating complicated myopia: ocular medicinal films with emoxipin and pyridoxine hydrochloride.


Superiority of preemptive donor lymphocyte infusion based on minimal residual disease in acute leukemia patients after allogeneic hematopoietic stem cell transplantation.
Donor lymphocyte infusion (DLI) was used as salvage therapy in leukemia relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT), but existing results on DLI administration to acute leukemia patients were disappointing. Although increasing minimal residual disease (MRD) after HSCT had been proven to be highly indicative of posttransplant relapse, preemptive DLI (pDLI) based on MRD has not been well evaluated. We retrospectively analyzed 70 acute leukemia patients after allo-HSCT in our center between January 2005 and December 2010. Sixteen patients received pDLIs based on increasing MRD results (pDLI group), and 11 relapsed patients received therapeutic DLIs with or without chemotherapy (tDLI group). Donor lymphocytes were collected from the original donors without stimulation and infused without further manipulation. The median mononuclear cell doses and CD3+ cell doses were 1.49 × 10(8) and 5.51 × 10(7) /kg. Forty-three patients who did not receive pDLI therapy after detecting increasing MRD (no pDLI group) were also included as a comparison. The response rate was 100% in the pDLI group, whereas it was 63.6% in the tDLI group (p=0.019). Survival outcomes were superior in the pDLI group compared with the tDLI group (χ(2) = 14.624, p=0.000); estimated overall survival (OS) at 1 year was 93.8% with pDLI and 27.3% with tDLI. The incidence of overall acute graft-versus-host disease (aGVHD) and Grade III to IV aGVHD was higher in the pDLI group but with no significance. Patients in the "no pDLI" group showed an inferior prognosis with 1-year OS at 65.1% (95% confidence interval, 50.8%-79.4%). Our results demonstrated the efficacy and safety of pDLI and suggested that pDLI based on MRD monitoring was superior in acute leukemia patients with potential progression compared with salvage DLI administrated in overt relapse.


[Bladder cleansing].
Bladder cleansings are administered in order to maintain the permeability of a probe and/or to eliminate an obstruction, be it a clot, urinary sand or detritus, by means of an infusion of intravenous fluid using sterile procedures through a bladder catheter. This is a technique frequently used with patients undergoing genital-urinary surgery; it is not recommended for routine usage due to its high risk of associated infection. Bladder cleansing can be continuous by means of a permanent bladder cleansing method or intermittent by means of an open or closed system.


An injectable, low-toxicity phospholipid-based phase separation gel that induces strong and persistent immune responses in mice.
Sustained antigen delivery using incomplete Freund's adjuvant (IFA) can induce strong, long-term immune response, but it can also cause severe side effects. Here we describe an injectable, phospholipid-based phase separation gel (PPSG) that readily transforms in situ into a drug depot. PPSG loaded with the model antigen ovalbumin (OVA) supported sustained OVA release in mice that lasted nearly one month. Immunizing mice with a single injection of PPSG/OVA elicited a strong and persistent increase in titers of OVA-specific IgG, IgG1 and IgG2a. Co-administering CpG-ODN further increased antibody titers. Such co-administration recruited dendritic cells to injection sites and activated dendritic cells in the draining lymph nodes. Moreover, immunization with PPSG/OVA/CpG resulted in potent memory antibody responses and high frequency of memory T cells. Remarkably, PPSG/OVA/CpG was associated with much lower toxicity at injection sites than IFA/OVA/CpG, and it showed no systemic toxicity such as to lymph nodes or spleen. These findings illustrate the potential of injectable PPSG for sustained, minimally toxic delivery of antigens and adjuvants.


Highly variable mRNA half-life time within marine bacterial taxa and functional genes.
Messenger RNA can provide valuable insights into the variability of metabolic processes of microorganisms. However, due to uncertainties that include the stability of RNA, its application for activity profiling of environmental samples is questionable. We explored different factors affecting the decay rate of transcripts of three marine bacterial isolates using qPCR and determined mRNA half-life time of specific bacterial taxa and of functional genes by metatranscriptomics of a coastal environmental prokaryotic community. The half-life time of transcripts from 11 genes from bacterial isolates ranged from 1 to 46 min. About 80% of the analysed transcripts exhibited half-live times shorter than 10 min. Significant differences were found in the half-life time between mRNA and rRNA. The half-life time of mRNA obtained from a coastal metatranscriptome ranged from 9 to 400 min. The shortest half-life times of the metatranscriptome corresponded to transcripts from the same clusters of orthologous groups (COGs) in all bacterial classes. The prevalence of short mRNA half-life time in genes related to defence mechanisms and motility indicate a tight connection of RNA decay rate to environmental stressors. The short half-life time of RNA and its high variability needs to be considered when assessing metatranscriptomes especially in environmental samples.


Pressure natriuresis and control of arterial pressure during chronic norepinephrine infusion.
The goal of this study was to quantitate changes in mean arterial pressure (MAP) and renal function during chronic increases in plasma levels of norepinephrine, and to determine the role of the renal pressure natriuresis mechanism in controlling sodium balance in norepinephrine hypertension. In six conscious dogs in which renal artery pressure (RAP) was allowed to increase during 7 days of norepinephrine infusion (0.2 micrograms/kg per min), sodium excretion (UNaV) rose from 66 +/- 3 to 112 +/- 15 mmol/day and MAP increased from 100 +/- 3 to 109 +/- 3 mmHg on the first day. On days 2-7, UNaV returned toward the control level while MAP averaged 108 +/- 2 mmHg. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) did not change significantly, averaging 85.9 +/- 4.0 and 235 +/- 17 ml/min, respectively, during 7 days of norepinephrine, compared to controls of 84.1 +/- 3.9 and 252 +/- 20 ml/min. When RAP was servo-controlled for 7 days during norepinephrine infusion, the natriuresis was abolished; UNaV averaged 76 +/- 8 during control, 77 +/- 13 during the first day of norepinephrine and 65 +/- 4 mmol/day during 7 days of norepinephrine. GFR and ERPF did not change significantly during norepinephrine infusion with RAP held constant. MAP did not reach a plateau but continued to rise from 102 +/- 3 to 137 +/- 3 mmHg after 7 days of norepinephrine and servo-control of RAP.(ABSTRACT TRUNCATED AT 250 WORDS)


Acne and its treatment options: a review.
Acne vulgaris is an extremely common condition affecting more than 80-90% of adolescents and young adults. It typically starts in late childhood or early teens, but onset may be delayed in some people well into their 20s and 30s. The incidence rate of acne is roughly the same in males and females but, males tend to have more serious conditions. Common therapies that are used for the treatment of acne include topical, systemic, herbal and combination therapies. This review is an attempt to trace out the causes of acne, to know its treatment options and precautions to be taken to prevent it.


Effectiveness of dentine bonding agents against cariogenic bacteria in vitro: a comparison of two methods.
Data obtained from studies on the antimicrobial properties of bonding agents are the subject of controversy, probably because of methodological differences. This study compared two commonly used in vitro methods, the disc agar diffusion test and the well agar diffusion test. Agar plates were seeded with Streptococcus sobrinus, Lactobacillus gasseri, or Actinomyces naeslundii. For the well diffusion test, wells cut out of the agar were filled with the test material, and for the disc method, discs impregnated with the test material were applied to the agar; the discs and wells were both 9 mm in diameter. After incubation, measurements of the zones of inhibition showed little agreement between the two methods when bonding agents were tested; the mean differences (+/- sdiff) in the zones of inhibition between the methods were 0.7 +/- 3.4 mm (P = 0.40, one sample t-test against zero), 4.9 +/- 4.4 mm (P = 0.97), and 0.8 +/- 4.3 mm (P = 0.47) for S. sobrinus, L. gasseri, and A. naeslundii, respectively. Mean differences were less contrasting when chlorhexidine and pure components were tested (P < 0.05 for S. sobrinus and L. gasseri). These results indicate the need for a gold standard method to evaluate the antimicrobial properties of bonding agents.


Differential cardiovascular and renal responses produced by microinjection of the {kappa}-opioid U-50488H [(trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzene-acetamide) methane sulfonate] into subregions of the paraventricular nucleus.
kappa-Opioids produce a centrally mediated diuresis, antinatriuresis, and renal sympathoexcitation in vivo; however, the specific brain sites mediating these responses are unknown. This study examined the role of the hypothalamic paraventricular nucleus (PVN) and the renal sympathetic nerves in mediating the cardiovascular and renal responses to central kappa-opioid receptor activation. In ketamine/xylazine-anesthetized rats, bilateral microinjection of the selective kappa-agonist U-50488H [(trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzene-acetamide) methane sulfonate; 100 ng] into the posterior magnocellular division of the PVN significantly increased urine flow rate (control, 47 +/- 9 microl/min; 40 min, 108 +/- 10 microl/min) without changing urinary sodium excretion or cardiovascular function. In other animals, microinjection of U-50488H into the same site elicited a similar water diuresis without a change in renal sympathetic nerve activity. In contrast, microinjection of U-50488H (100 ng) into the parvocellular PVN produced an immediate pressor response (Delta 16 +/- 3 mm Hg) that occurred with a potential baroreflex evoked bradycardia (Delta -26 +/- 8 beats per minute), renal sympathoinhibition (Delta -18 +/- 4%), natriuresis (Delta 38 +/- 1%), and delayed (30-min) antidiuresis (Delta -22 +/- 9%). These results were prevented by pretreatment with the kappa-receptor antagonist nor-binaltorphimine and were not obtained when U-50488H was injected outside the PVN, or when vehicle was injected into the PVN. Together, these results demonstrate that the posterior magnocellular PVN is a brain site where central kappa-opioids act to produce diuresis, presumably by inhibiting the secretion of arginine vasopressin. Alternatively, central kappa-opioids evoke antinatriuresis via augmenting renal sympathetic nerve activity and/or other neurohumoral sodium retaining pathways at brain sites other than the hypothalamic PVN.


Systemic sclerosis. A vascular perspective.
The horizon is bright for SSc in a vascular context. Surrogate markers can now be routinely used in the management of the active patient; new cytokines, such as VEGF, can be studied along with the known abnormalities of the cytokine cascade (TGF beta 1, PDGF) for a more integrated understanding of the vascular pathogenesis of SSc (Fig. 6); and combination therapies can be applied before vascular insufficiency leads to vital organ failure. Thus, despite reimbursement and research funding constraints, the future for both the SSc patient and the investigator of SSc is optimistic when based on a firm biologic foundation.


Japanese experience with second-line chemotherapy with low-dose (60 mg/M2) docetaxel in patients with advanced non-small-cell lung cancer.
To assess the efficacy and toxicity of relatively low-dose docetaxel (60 mg/m2) for previously treated advanced non-small-cell lung cancer (NSCLC). Patients with advanced (clinical stage IIIA-IV) NSCLC who had previously undergone at least one series of chemotherapy were enrolled. Previous paclitaxel use was allowed, but docetaxel was not. Docetaxel was administered at an initial dose of 60 mg/m2 intravenously on day 1 over 90 min every 3 weeks. From June 1997 to November 1999, 22 patients were entered into this study. The total number of cycles delivered to 22 patients was 53, with a median per patient of 2. Four patients achieved a partial response (PR), and the overall response rate was 18.2% (95% confidence interval 5.1-40.3%). The median time to progression was 13.7 weeks. The median survival time was 7.8 months, and the 1-year survival rate was 25%. About 73% of patients experienced grade 3 or 4 neutropenia. Neutropenic fever was observed in four patients (18%). Non-hematologic toxicities were generally mild. No treatment-related deaths occurred. Although the validity of the results of this study is limited due to the small and monoracial study population examined, low-dose (60 mg/m2) docetaxel for previously treated advanced NSCLC appears to yield antitumor activity and survival benefit comparable to those obtained with the conventional dose (100 mg/m2).


[BbvII--a new site-specific endonuclease from Bacillus brevis 80].
BbvII, a new site-specific endonuclease, has been isolated from Bacillus brevis 80 by gel-filtration and chromatography on heparin-Sepharose. The endonuclease recognizes a non-symmetrical sequence 5'-GTCTTC-3' in double-stranded DNA and cleaves DNA 3'-CAGAAG-5' in both strands outside the recognition sequence.


Preparation needed for the social dimensions of epidemics in Africa: Experience from a training session in Conakry.
After the Ebola outbreak in West Africa (2013-2016), preparedness is on the agenda of health institutions. However, key questions remain about the scope of preparedness and activities related to the socio-cultural dimension of epidemics. A multidisciplinary short-course Infectious Diseases and Anthropology in West Africa (MIAA) was held at CERFIG, Conakry, in November 2017. Its evaluation provides some answers to key questions, such as who should be trained, and what its objectives, pedagogical contents, and methods should be.


Changes in frontal morphology after single-stage open posterior-middle vault expansion for sagittal craniosynostosis.
There is controversy regarding whether the frontal bossing associated with sagittal synostosis requires direct surgical correction or spontaneously remodels after isolated posterior cranial expansion. The authors retrospectively measured changes in frontal bone morphology in patients with isolated sagittal synostosis 2 years after open posterior and midvault cranial expansion and compared these changes with those occurring in age-comparable healthy control groups. Forty-three patients age 1 year or younger (mean, 6 months) with sagittal synostosis underwent computed tomography scan digital analysis immediately after and 2 years after posterior-middle cranial vault expansion. Quantitative angular and linear measures were taken along the midsagittal and axial planes to capture both aspects of frontal bossing. The change in values over the 2 years were compared with healthy controls with normal computed tomography scans taken to rule out head trauma. All measures indicative of frontal bossing decreased significantly from the time of posterior-middle vault expansion to 2 years postoperatively. Whereas the majority of patients at time of the operation had frontal bossing measures greater than two standard deviations outside the age-comparable control mean, almost all patients were within two standard deviations of the norm 2 years later. Lateral forehead bossing and anterior cranial growth was greater the older the patient was at the time of the operation, suggesting that the more time that passed before the operation, the more compensatory anterior fossa growth occurred. Central forehead position relative to the anterior cranial base was greatest in the younger patients at the time of operation, suggesting that a central forehead bulge was an early compensatory response to premature sagittal fusion. As a group, patients with sagittal synostosis start to normalize their forehead morphology within 2 years if an isolated posterior operation is performed at 1 year of age or younger, and this occurs by a combination of restriction of growth and reduction relative to patients without synostosis. This protocol decreases the risks of intraoperative positioning, forehead contour deformities, and two-stage operations. Therapeutic, III.


Upregulation of microRNA-21 is a poor prognostic marker in patients with childhood B cell acute lymphoblastic leukemia.
Many studies have demonstrated that microRNA-21 (miR-21) is an oncogene and is upregulated in tumor tissue. However, its association with B-cell acute lymphoblastic leukemia (B-ALL) remains poorly understood. The expression of miR-21 was detected by real-time quantitative PCR in 75 children with de novo B-ALL as well as in 50 healthy controls. This study was conducted to evaluate the miR-21 as a biomarker for risk assessment, diagnosis and prognosis. Compared with normal controls, miR-21 expression was significantly upregulated in childhood B-ALL patients. Using the receiver operating characteristic curve 3.23 was selected as the cut-off value of miR-21 expression in distinguishing patients from controls. Patients group with High miR-21 expression was significantly associated with those aged <2 and >10 years, lower platelets count, more incidence of CNS infiltration and poorer treatment outcome also, they showed a significantly poorer disease-free survival (DFS) and overall survival (OS) compared to those with low miR-21 expression group. Its expression was an independent prognostic marker according to multivariate analysis. This is the first report demonstrating the upregulation of miR-21 in childhood B-ALL, and its association with poor response to induction therapy, shorter DFS and OS. These results suggest that miR-21 upregulation represent an unfavorable prognostic marker in Childhood B-ALL.


Cerebrospinal fluid neopterin in human immunodeficiency virus type 1 infection.
We evaluated cerebrospinal fluid (CSF) concentrations of neopterin, a putative marker of activated macrophages, in 97 subjects infected with human immunodeficiency virus type 1 who had a spectrum of neurological complications. The highest CSF neopterin concentrations occurred in those with neurological opportunistic infections, primary central nervous systems lymphoma, and acquired immunodeficiency syndrome (AIDS) dementia complex. In general, the CSF concentration of neopterin was independent of CSF cell count and blood-brain barrier disruption to albumin. In the patients with AIDS dementia complex, CSF neopterin concentrations correlated with severity of disease and decreased in conjunction with clinical improvement following treatment with zidovudine. These results suggest that CSF neopterin, although not disease-specific, may be useful as a surrogate marker for the presence of AIDS dementia complex and its response to antiviral therapy.


Immunocytochemical localization of border disease virus in the spinal cord of fetal and newborn lambs.
The peroxidase-antiperoxidase technique was used to determine the cellular localization of Border Disease (BD) virus in cryostat sections of fetal and newborn lamb spinal cord following experimental infection by maternal inoculation in early gestation. Viraemic fetuses and lambs with hypomyelinogenesis showed BD viral antigen in neurons, glia, ependymal cells, vascular endothelial cells and fibrocytes within the dura mater. Double immunolabelling demonstrated co-expression of BD viral antigen and glial fibrillary acidic protein (GFAP) or myelin basic protein (MBP) in both fetal and newborn lamb glia. In fetal lambs there was a pia-associated population of glia in which viral antigen was also co-expressed with GFAP or MBP. The results suggest that BD virus infects myelinating oligodendroglia, astroglia and probably also transitional cells and pluripotential glioblasts. The relationship between infection of specific cell types and hypomyelinogenesis was not resolved but infection of transitional cells and oligodendroglia may affect oligodendroglial function and permit morphologically inapparent perturbations leading to hypomyelinogenesis. A single nonviraemic lamb with a precolostral antibody titre to BD virus and cystic cerebral cavities but no hypomyelinogenesis showed BD viral antigen confined to glia of the spinal cord white matter. This suggests that oligodendroglia may require to be infected before a critical period in their development or factors additional to oligodendroglia infection are necessary for hypomyelinogenesis.


Pharmacotherapy of personality disorders: conceptual framework and clinical strategies.
This article delineates the conceptual models used when medications are prescribed for patients with personality disorders and reviews the data on the efficacy of these medications. Studies before 1980 are difficult to interpret because of changes in diagnostic criteria. Nonetheless, early studies on non-DSM-III disorders such as pseudoneurotic schizophrenia, emotionally unstable character disorder, hysteroid dysphoria, and subaffective disorders indicated the potential utility of pharmacotherapy for treating personality disorders. Models to consider in evaluating the possible use of medications for treating personality disorders are: (1) treating the disorder itself; (2) treating symptom clusters within and across disorders; and (3) treating associated axis I disorders. Among the current personality disorders, borderline personality disorder has been the most extensively studied, with antipsychotic agents being the most well-documented treatment. Monoamine oxidase inhibitors, fluoxetine, and carbamazepine show promise. Schizotypal disorders may respond to low-dose antipsychotic drugs. Although heuristically valuable, the symptom cluster approach to treatment has not yet been validated. Axis I disorders, especially depression, are frequently associated with all personality disorders. Dependent personality disorder is linked to panic disorder with agoraphobia, whereas avoidant personality disorder is associated with social phobia and panic. In general, pharmacotherapy for axis I disorders is less effective in the presence of a comorbid personality disorder. Despite the modest benefits seen in many studies, pharmacotherapy can add significantly to the overall treatment of those with personality disorders. Future research must carefully assess the effect of comorbid axis I disorders on responses. The symptom cluster/psychobiologic dimension approach should be investigated in clinical studies.


Eubacterium plautii infection in a kidney transplant recipient: a noteworthy case of pleural effusion and fever.
We report a noteworthy case of Eubacterium plautii infection after kidney transplantation. Our 33-yr-old transplant recipient received standard care; his post-transplant course was uneventful. However, on day 44 he underwent an emergency laparotomy for perforation of the ileum. He was initially treated with ceftazidime, fluconazole and metronidazole, but his fever persisted, so he was switched to meropenem and vancocin. We could not find any cause for his infection. On day 70, his temperature normalized. On day 75, he developed severe leukopenia (280 cell/mL). His cytomegalovirus-DNA test result was negative, so all immunosuppressants, except for prednisone, were stopped; instead, antibiotic prophylaxis was started, using caspofungin, trimethoprim-sulfamethoxazole and ciprofloxacin. On day 83, he underwent percutaneous drainage of massive left pleural effusion. We repeatedly cultured the pleural liquid, but it was not till three wk later that we were finally able to identify the causative organism. We hypothesize that the microorganism - which normally resides on the surface of the intestinal lumen - entered the bloodstream via bacterial translocation, eventually colonizing the pleurae. This translocation was favored by our patient poor clinical condition, his immunosuppressive treatment and his heavy antibiotherapy. Our experience highlights the need for wiser use of antibiotics in transplant recipients.


Patterns of adverse childhood experiences and subsequent risk of interpersonal violence perpetration among men in Dar es Salaam, Tanzania.
Adverse childhood experiences (ACEs), including abuse and neglect, are consistently found to be predictors of perpetration of intimate partner violence (IPV) and peer violence (PV) in adulthood. Children are often exposed to patterns of ongoing and/or multiple-type polyvictimization throughout the life course. To identify and characterize patterns of ACEs among men in Dar es Salaam, Tanzania and to examine the relationship between these patterns and perpetration of intimate partner violence (IPV) and peer violence (PV) in adulthood. We used latent class analysis to identify respondents with similar patterns of ACEs. The analysis was conducted with a sample of 987 men. We uncovered five distinct classes of men with specific patterns of ACEs. One consisted of nonvictims and four included various forms of polyvictimization. Men in the polyvictimization classes that included non-violent family dysfunction had significantly higher odds of perpetrating psychological IPV compared to the other three classes (AORs 2.33 and 3.04 compared to nonvictims). Men in the polyvictimization classes that included any sexual violence and/or non-violent family dysfunction had significantly higher odds of perpetrating PV compared to the other two classes (AORs 3.54, 6.10, and 7.42 compared to nonvictims). These findings suggest that distinct patterns of exposure to ACEs among this population are differentially related to perpetration of IPV and PV in adulthood. These findings highlight the importance of child development interventions in low-and middle-income countries, both for the primary prevention of child adversity and for mitigation of the cognitive and emotional effects of ACEs.


Glial Attenuation With Ibudilast in the Treatment of Medication Overuse Headache: A Double-Blind, Randomized, Placebo-Controlled Pilot Trial of Efficacy and Safety.
Medication overuse headache (MOH) is a condition bordering between a chronic pain condition and a substance dependence disorder. Activation of immunocompetent glial cells in the central nervous system has been linked to both pathological pain and drug addiction/reward. Preclinically, ibudilast attenuates glial activation and is able to reduce neuropathic pain and markers of substance dependence. We therefore hypothesized ibudilast would reduce headache burden and opioid analgesic requirements in patients with opioid overuse headache. To determine if treatment with ibudilast provides a greater reduction in headache index than placebo in MOH patients consuming opioids. Participants with MOH who were using opioids were randomized via computer-generated code to ibudilast 40 mg or placebo twice daily for 8 weeks in a double-blind, parallel groups study. Before randomization participants completed a 4-week baseline headache diary. During treatment, headache diary data collection continued and participants attended 4 study visits during which quantitative sensory testing was performed. Blood samples for immune biomarker analyses were collected before and after treatment in a subgroup of participants. Thirty-four participants were randomized, 13 of 15 randomized to ibudilast and 17 of 19 randomized to placebo completed treatment. Ibudilast was generally well-tolerated with mild, transient nausea reported as the most common adverse event (66.7% vs 10.5% in placebo group). Results are shown as mean (SD). At the end of treatment no differences in the primary outcome average daily headache index (placebo 62 [44] vs ibudilast 77 [72] groups, difference -15, CI -65 to 35 h × numerical rating scale), or secondary outcomes headache frequency (placebo 23 [8.1] vs ibudilast 24.5 [6.2], difference -1.5, CI -7.7 to 4.8 days/month) and opioid intake (placebo 20.6 [43] vs ibudilast 19 [24.3], difference 1.6, CI -31.5 to 34.8 mg morphine equivalent) were observed between placebo and ibudilast groups. Using the current dosing regimen, ibudilast does not improve headache or reduce opioid use in patients with MOH without mandated opioid withdrawal. However, it would be of interest to determine in future trials if ibudilast is able to improve ease of withdrawal during a forced opioid down-titration when incorporated into an MOH detoxification program.


Emotion recognition in children with autism spectrum disorders: relations to eye gaze and autonomic state.
Respiratory Sinus Arrhythmia (RSA), heart rate, and accuracy and latency of emotion recognition were evaluated in children with autism spectrum disorders (ASD) and typically developing children while viewing videos of faces slowly transitioning from a neutral expression to one of six basic emotions (e.g., anger, disgust, fear, happiness, sadness, and surprise). Children with ASD were slower in emotion recognition and selectively made more errors in detecting anger. ASD children had lower amplitude RSA and faster heart rate. Within the ASD group, children with higher amplitude RSA recognized emotions faster. Less severe ASD symptoms and increased gaze to the eye region in children with ASD were related to more accurate emotion recognition.


Campomelic syndrome--laryngotracheomalacia treated with single-stage laryngotracheal reconstruction.
The campomelic syndrome is a rare osteochondrodysplasia which frequently leads to early death from pulmonary insufficiency. We describe a patient with anatomic compromise of the upper airway due to diffuse laryngotracheomalacia and a moderate subglottic stenosis, treated successfully with single-stage laryngotracheal reconstruction using a rib graft. To our knowledge this has not been previously described. A review of the current literature is included.


[Ultrasonic diagnosis of complications after bypass operations in lower extremities arteries].
After reconstructive vascular operations the patients need dynamic control and non-invasive monitoring. The purpose of the study was to reveal the potential of duplex scanning (DS) in assessment of bypasses function and diagnosis of postoperative complications. 148 patients after aorto-femoral and femoro-popliteal bypass, including patients with late postoperative complications (shunt thrombosis, stenosis or spurious aneurysm of anastomosis) were examined. Energy colored DS was performed in scans "Toshiba" SSH-140 and "Acuson" Sequoia-512. In ultrasonic diagnosis the vascular graft was imaged as a tube structure with hyperechogenic walls and distinct pulse; it was easy to detect the material of vascular graft. In examination of distal anastomosis the initial portions of efferent arteries were usually imaged distinctly. In satisfactory distal vascular bed, the shunt's blood flow did not differ from normal blood flow. In patients with multifocal lesions the spectrum of shunt's blood flow was similar to main-changed blood flow. Substantial change of blood velocity was revealed in complications (aneurysm or stenosis of anastomosis). Spurious aneurysm was imaged as a hypoechogenic pulsating formation. Thrombotic masses in aneurysm's cavity were distinctly detected at DS, unlike at angiography. In case of anastomosis insufficiency, the suture's disrupted filaments and free branch's ends could be imaged. Stenosis of anastomosis was characterized by visible lumen's stenosis, local thickening and unevenness of wall, spectrum's change and blood velocity increase. In shunt's thrombosis the DS permitted to follow the thrombed graft's path, to reveal the cause of thrombosis and to detect the condition of outflow tract. The authors regard DS as a method of choice in dynamic control for state of bypasses and arteries in patients after reconstructive operations in lower extremities arteries.


Uptake and binding of serotonin by primary cultures of mouse astrocytes.
Primary cultures of glia contain a high glial fibrillary acidic protein level and exhibit important glutamine synthetase activity. They take up serotonin via a high affinity carrier-mediated system with a Km of micromolar range. The Km of this transport process does not vary during cell growth or maturation; however, during the last period of morphological change induced by dibutyryl cyclic AMP, an increase in Vmax is observed. Chlorimipramine, fluoxetine and fenfluramine at 10-4 M inhibit this uptake. 3H-5-HT still binds to partially purified astrocytic membranes on a single type of site. During growth, neither KD nor Bmax were modified. During the maturation period, KD decreased to about 50% of its control level. Methysergide inhibits that binding.


Stepwise thickening in aqueous foam films stabilized by sodium naphthenates.
During drainage of a foam film formed from an aqueous sodium naphthenate solution, a transient, local, stepwise thickening process was observed. Film stratification is related to the stepwise thinning drainage process where individual layers of material are drained from a film. The process typically involves the appearance of a sequence of small, uniformly thick spots that eventually expand to the size of the film. The appearance and growth of each spot represents a discrete decrease in the thickness of the film. The size of each decrease or step typically corresponds to the size of one or more lamella layers of the stratified film. Stepwise thinning was observed in a foam film formed from an aqueous sodium naphthenate solution, as frequently reported for a variety of systems. However, during the drainage process, a transient stepwise thickening process was also observed. Bright spots began to appear and grow, indicate a discrete increase in the thickness of a portion of the film. This local, stepwise thickening process appeared to be an alternate and temporary drainage process directly related to the expansion of the stepwise thinning spots.


Optimization of the ethanolysis of Raphanus sativus (L. Var.) crude oil applying the response surface methodology.
Raphanus sativus (L. Var) is a perennial plant of the Brassicaceae (or Cruciferae) family whose oil has not been investigated in detail for biodiesel production, particularly when ethanol is used as the alcoholysis agent. In this work, response surface methodology (RSM) was used to determine the optimum condition for the ethanolysis of R. sativus crude oil. Three process variables were evaluated at two levels (2(3) experimental design): the ethanol:oil molar ratio (6:1 and 12:1), the catalyst concentration in relation to oil mass (0.4 and 0.8 wt% NaOH) and the alcoholysis temperature (45 and 65 degrees C). When the experimental results were tentatively adjusted by linear regression, only 58.15% of its total variance was explained. Therefore, a quadratic model was investigated to improve the poor predictability of the linear model. To apply the quadratic model, the 2(3) experimental design had to be expanded to a circumscribed central composite design. This allowed the development of a response surface that was able to predict 97.75% of the total variance of the system. Validation was obtained by performing one ethanolysis experiment at the conditions predicted by the model (38 degrees C, ethanol:oil molar ratio of 11.7:1 and 0.6 wt% NaOH). The resulting ester yield (104.10 wt% or 99.10% of the theoretical yield of 105.04 wt%) was shown to be the highest among all conditions tested in this study. The second ethanolysis stage of the best RSM product required 50% less ethanol and 90% less catalyst consumption. The amount of ethyl esters obtained after this procedure reached 94.5% of the theoretical yield. The resulting ethyl esters were shown to comply with most of the Brazilian biodiesel specification parameters except for oxidation stability. Addition of 500 ppm of BHT to the esters, however, complied with the specification target of 6h. The application of 2 wt% Magnesol after the second ethanolysis stage eliminated the need for water washing and helped generate a final product with less unreacted glycerides.


Water holding capacity and collagen profile of bovine m. infraspinatus during postmortem ageing.
Changes in the water holding capacity (WHC) and collagen profile in bovine m. infraspinatus during ageing in a vacuum at 3 °C up to 20 days were studied. Moisture, expressible water and total collagen content were determined in raw samples and muscles were then subjected to thermal treatment in steam. Moisture, collagen fractions (total, water-soluble, insoluble, acetic acid-soluble, total soluble) and cooking loss were determined in the cooked meat. Ageing time did not significantly influence WHC (expressible water content as a % of moisture), moisture content in raw and cooked meat or cooking loss. Between the 5th and 10th day of ageing a significant increase was noted in acetic acid-soluble collagen and total soluble collagen content along with a decrease in insoluble collagen content (p b 0.05). A significant negative relationship was found between the expressible water content and the water-soluble collagen. It was concluded that connective tissue ageing of bovine m. infraspinatus might be finished after 10 days.


Fos is phosphorylated by p34cdc2, cAMP-dependent protein kinase and protein kinase C at multiple sites clustered within regulatory regions.
The proto-oncogene c-fos encodes a nuclear protein (Fos) that functions in transcriptional regulation in response to extracellular signals. Fos is extensively modified in the nucleus by serine and threonine phosphorylation. It has been suggested that phosphorylation may play an important role in regulating Fos function in normal and transformed cells. As a first step in addressing this issue, we have used purified Fos as a substrate for several serine-threonine protein kinases, including cAMP-dependent protein kinase (PKA), protein kinase C (PKC) and p34cdc2. Each of these kinases phosphorylated Fos at several unique sites. These sites were located within two regions that were previously shown to reduce the transcriptional activity of Fos in vitro. Several of the sites modified in vitro were also shown to be phosphorylated in serum-stimulated fibroblasts. These findings demonstrate that Fos is a target for several protein kinases involved in signal transduction and suggest that phosphorylation could regulate the transcriptional properties of Fos.


Ichthyosiform scaling in association with lymphoma.
A patient is described who developed ichthyosiform scaling in association with localized Hodgkin's disease. The scaling subsequently cleared following initial successful radiotherapy of the tumor. The scaling has not returned with two recurrences of the lymphoma during a five-year period.


Cytokeratin 15 can be used to identify the limbal phenotype in normal and diseased ocular surfaces.
To elucidate the expression pattern of K15, K19, K14, and K12 in human and mouse ocular surface epithelium as putative markers of epithelial phenotype. Immunohistochemical staining with specific antibodies for K15, K19, K14, and K12 was performed in human donor cornea tissue and normal ICR mouse corneas, with emphasis on localization of immunopositive cells. Immunohistochemistry was performed in a limbus-deficient mouse model as well as in clinical samples of pannus surgically removed from a thermal burn and a patient with Saltzmann's dystrophy. Staining patterns were classified as limited to the most basal layer (K(bas)), basal and suprabasal layers (K(bas-sup)), predominantly in suprabasal layers (K(sup)) and negative staining (K(-)). In human conjunctival epithelium, strong expression of K15 was observed in basal cells, whereas K19 was expressed in both basal and suprabasal layers (K15(bas)/K19(bas-sup)/K12(-)). Limbal epithelial cells were K15(bas-sup)/K19(bas-sup)/K12(sup), whereas epithelial cells in the central cornea were K15(-)/K19(bas-sup)/K12(bas-sup). In contrast, the mouse ocular surface demonstrated a different expression pattern of K15 and K19 than did the human tissue in the conjunctiva (K15(bas-sup)/K19(bas)/K12(-)) and the limbus (K15(bas-sup)/K19(bas)/K12(sup)). Neither K15 nor K19 was expressed in the central mouse cornea (K15(-)/K19(-)/K12(bas-sup)). Similar cytokeratin expression was observed in conjunctivalized corneas in mice and in surgically removed pannus tissue. Although the expression of K15 and K19 differ in humans and mice, specific staining patterns can be used to characterize the epithelial phenotype in normal and diseased ocular surface.


Possible involvement of type 1 inositol 1,4,5-trisphosphate receptors up-regulated by dopamine D1 and D2 receptors in mouse nucleus accumbens neurons in the development of methamphetamine-induced place preference.
Little is known about regulatory mechanisms of type 1 inositol-1,4,5-triphosphate receptor (IP(3)R-1) expression in conditioned place preference by methamphetamine (METH), though significant enhancement of IP(3)R-1 expression in the mouse frontal cortex and limbic forebrain by intermittent administration of cocaine is reported. The present study investigated the role and regulation of IP(3)R-1 in mice with METH-induced place preference. Injection of IP(3)R antagonists with different chemical structures, 2-aminophenoxyethane-borate and xestospongin C, into the mouse nucleus accumbens (NAcc) dose-dependently inhibited METH-induced place preference. The levels of IP(3)R-1 protein in the NAcc of METH-conditioned mice significantly increased, which was completely abolished by microinjection of SCH23390 and raclopride, selective dopamine D1-like and D2-like receptor (D1 and D2DR) antagonists respectively, into the mouse NAcc. Immunohistochemical assessment revealed co-localization of immunoreactivity for IP(3)R-1 and those for D1 and D2DRs in the NAcc. These findings suggest that IP(3)R-1 could be involved in the development of METH-induced place preference and that D1 and D2DRs in the NAcc of mice showing METH-induced place preference play possible regulatory roles in IP(3)R-1 expression.


Chronic stress-induced memory deficits are reversed by regular exercise via AMPK-mediated BDNF induction.
Chronic stress has a detrimental effect on neurological insults, psychiatric deficits, and cognitive impairment. In the current study, chronic stress was shown to impair learning and memory functions, in addition to reducing in hippocampal Adenosine monophosphate-activated protein kinase (AMPK) activity. Similar reductions were also observed for brain-derived neurotrophic factor (BDNF), synaptophysin, and post-synaptic density-95 (PSD-95) levels, all of which was counter-regulated by a regime of regular and prolonged exercise. A 21-day restraint stress regimen (6 h/day) produced learning and memory deficits, including reduced alternation in the Y-maze and decreased memory retention in the water maze test. These effects were reversed post-administration by a 3-week regime of treadmill running (19 m/min, 1 h/day, 6 days/week). In hippocampal primary culture, phosphorylated-AMPK (phospho-AMPK) and BDNF levels were enhanced in a dose-dependent manner by 5-amimoimidazole-4-carboxamide riboside (AICAR) treatment, and AICAR-treated increase was blocked by Compound C. A 7-day period of AICAR intraperitoneal injections enhanced alternation in the Y-maze test and reduced escape latency in water maze test, along with enhanced phospho-AMPK and BDNF levels in the hippocampus. The intraperitoneal injection of Compound C every 4 days during exercise intervention diminished exercise-induced enhancement of memory improvement during the water maze test in chronically stressed mice. Also, chronic stress reduced hippocampal neurogenesis (lower Ki-67- and doublecortin-positive cells) and mRNA levels of BDNF, synaptophysin, and PSD-95. Our results suggest that regular and prolonged exercise can alleviate chronic stress-induced hippocampal-dependent memory deficits. Hippocampal AMPK-engaged BDNF induction is at least in part required for exercise-induced protection against chronic stress.


Laminectomy, durotomy, and piotomy effects on spinal cord intramedullary pressure in severe cervical and thoracic kyphotic deformity: a cadaveric study.
Previous studies have shown that cervical and thoracic kyphotic deformity increases spinal cord intramedullary pressure (IMP). Using a cadaveric model, the authors investigated whether posterior decompression can adequately decrease elevated IMP in severe cervical and thoracic kyphotic deformities. Using an established cadaveric model, a kyphotic deformity was created in 16 fresh human cadavers (8 cervical and 8 thoracic). A single-level rostral laminotomy and durotomy were performed to place intraparenchymal pressure monitors in the spinal cord at C-2, C4-5, and C-7 in the cervical study group and at T4-5, T7-8, and T11-12 in the thoracic study group. Intramedullary pressure was recorded at maximal kyphosis. Posterior laminar, dural, and pial decompressions were performed while IMP was monitored. In 2 additional cadavers (1 cervical and 1 thoracic), a kyphotic deformity was created and then corrected. The creation of the cervical and thoracic kyphotic deformities resulted in significant increases in IMP. The mean increase in cervical and thoracic IMP (change in IMP [ΔIMP]) for all monitored levels was 37.8 ± 7.9 and 46.4 ± 6.4 mm Hg, respectively. After laminectomies were performed, the mean cervical and thoracic IMP was reduced by 22.5% and 18.5%, respectively. After midsagittal durotomies were performed, the mean cervical and thoracic IMP was reduced by 62.8% and 69.9%, respectively. After midsagittal piotomies were performed, the mean cervical and thoracic IMP was reduced by 91.3% and 105.9%, respectively. In 2 cadavers in which a kyphotic deformity was created and then corrected, the ΔIMP increased with the creation of the deformity and returned to zero at all levels when the deformity was corrected. In this cadaveric study, laminar decompression reduced ΔIMP by approximately 15%-25%, while correction of the kyphotic deformity returned ΔIMP to zero. This study helps explain the pathophysiology of myelopathy in kyphotic deformity and the failure of laminectomy alone for cervical and thoracic kyphotic deformities with myelopathy. In addition, the study emphasizes the need for correction of deformity during operative treatment of kyphotic deformity, the need for maintaining adequate intraoperative blood pressure during operative treatment, and the higher risk of spinal cord injury associated with operative treatment of kyphotic deformity.