[Comparison of the effects of 2 preparations of cyclosporin A-- Consupren and Sandimmune--from the aspect of functional and morphologic changes in rats with renal ischemia].
Cyclosporine A is in transplantology an irreplaceable immunosuppressive agent. Its only manufacturer preparation Sandimmune--was the Swiss firm Sandoz. In 1990 the Czech firm Galena introduced cyclosporine A with the name Consupren on the market. The objective of the present investigation was to assess whether the nephrotoxic effect of the two preparations is comparable, or whether it differs. In a group of 65 rats after unilateral nephrectomy and 45-minute ischaemia of the remaining kidney the nephrotoxic action of cyclosporine preparations Sandimmune (Sandoz) and Consupren (Galena, CZ) administered in doses of 10 mg/kg body weight/24 hours throughout the experiment was investigated. The functional and morphological examination was made 3 or 21 days following nephrectomy. After three days the serum levels of creatinine, urea, sodium, osmolality and their urinary excretion as well as the intensity of proteinuria and morphological findings using light and electron microscopy did not differ in the two groups. The same was found during follow-up after 21 days; the small difference in the serum creatinine level only (Sandimmune 96.0 +/- 9.7 mumol/l, Consupren 111.4 +/- 11.2 mumol/l; p < 0.005) may be associated with the significantly higher cyclosporin levels following Consupren administration. The findings of the investigation support the idea that even after ischaemic kidney damage the nephrotoxicity of Consupren is not higher than that of Sandimmune.


Structural modification of the highly potent peptide bradykinin B1 receptor antagonist B9958.
Bradykinin (BK)-related peptides stimulate two major classes of receptors, B1 and B2. The B1 receptor (B1R) plays an important role in various pathophysiological states including chronic inflammation, pain, hypotension, trauma and proliferation of cancer. Therefore, there is interest in the development of highly potent peptide BK B1R antagonists. We previously developed a highly potent and selective BK B1R receptor antagonist, B9958 (Lys-Lys-[Hyp3, CpG5, d-Tic7, CpG8]des-Arg9-BK) (Hyp, trans-4-hydroxyproline; CpG, alpha-cyclopentylglycine; Tic, tetrahydroisoquinoline-3-carboxylic acid). We now report on new BK B1R antagonist analogs of B9958 with N-terminal basic residues in the d-configuration, or Lys-, Orn- derivatives (NiK, epsilon-nicotinoyllysine; PzO, 3-pyrazinoylornithine) and/or having hindered unusual amino acids at position 5 (Igl, alpha-(2-indanyl)glycine). These changes were designed to prevent enzyme degradation while keeping an acceptable affinity. However, these new analogs do not show higher B1R antagonist activity than B9958, but its N-terminal acylated derivative with a bulky and hydrophobic 2,3,4,5,6-pentafluorocinnamic acid (F5c), B10324, retains a B1R antagonist activity close to that of B9958 and, in addition, has high inhibition in vivo against lung cancer (SCLC, 86 %) and moderate inhibition against prostate cancer (PC3, 43%) xenografts. This class of compounds offers hope for the development of new BK antagonist peptide drugs for lung or prostate cancer.


[Novelties and new possibilities in radiological diagnostics of brain tumors].
Modern MR imaging with advanced techniques such as diffusion, perfusion and functional imaging as well as spectroscopy have improved the characterization of brain tumors. Unlike conventional imaging providing mainly anatomical or structural information, these advanced applications give insight into the microstructure and physiology of brain tumors. Several biomarkers are available which correlate with tumor cellularity, microstructure, vascularity and metabolism. These techniques not only aid in the imaging diagnosis and treatment planning of brain tumors, but they also play a role in clinical management and monitoring treatment effect.


Lamotrigine: a review of clinical studies in bipolar disorders.
This article reviews published studies on the use of lamotrigine in the treatment of bipolar disorder (BD). We performed a Medline search to identify the literature data base available on double-blind, open-label studies and case series on the use of lamotrigine to treat BD. Three double-blind studies, 3 open-label studies, and 2 case series have been conducted to date (n = 401 patients). Most patients were either nonresponders or partial responders to other mood stabilizers. Overall, 50% to 83% of the patients responded to lamotrigine; doses in the studies ranged from 50 to 400 mg daily. Switching to mania while on 200 mg of lamotrigine or more was extremely rare, and there were no reports of serious adverse effects during the study periods. Lamotrigine is proving to be an effective agent in the treatment of BD and may be useful for patients who have not responded to other mood stabilizers.


Quality-of-life analysis of the MITO-8, MaNGO, BGOG-Ov1, AGO-Ovar2.16, ENGOT-Ov1, GCIG study comparing platinum-based versus non-platinum-based chemotherapy in patients with partially platinum-sensitive recurrent ovarian cancer.
MITO-8 showed that prolonging platinum-free interval by introducing non-platinum-based chemotherapy (NPBC) does not improve prognosis of patients with partially platinum-sensitive recurrent ovarian cancer. Quality of life (QoL) was a secondary outcome. Ovarian cancer patients recurring or progressing 6-12 months after previous platinum-based chemotherapy (PBC) were randomized to receive PBC or NPBC as first treatment. QoL was assessed at baseline, third and sixth cycles, with the EORTC C-30 and OV-28 questionnaires. Mean changes and best response were analysed. Progression-free survival, response rate, and toxicity are also reported for proper interpretation of data. All analyses were based on intention-to-treat. Out of the 215 patients, 151 (70.2%) completed baseline questionnaire, balanced between the arms; thereafter, missing rate was higher in the NPBC arm. At mean change analysis, C30 scores were prevalently worse in the NPBC than PBC arm, statistical significance being attained for emotional functioning, global health status/QoL, fatigue, and dyspnoea (effect sizes ranging from 0.30 to 0.51). Conversely, as for OV28 scale, the other chemotherapy side-effects item was significantly worse with PBC at three and six cycles, with a larger effect size (0.70 and 0.54, respectively). At best response analysis, improvement of emotional functioning and pain and worsening of peripheral neuropathy and other chemotherapy side-effects were significantly more frequent in the PBC arm. Progression-free survival (median 9 versus 5 months, P = 0.001) and objective response rate (51.6% versus 19.4%, P = 0.0001) were significantly better with PBC. Allergy, blood cell count, alopecia, nausea, musculoskeletal, and neurological side-effects were more frequent and severe with PBC; hand-foot skin reaction, rash/desquamation, mucositis, and vascular events were more frequent with NPBC. MITO-8 QoL analysis shows that deterioration of some functioning and symptom scales is lower with PBC, with improvement of emotional functioning and pain, despite worsening of toxicity-related items. NCT00657878.


[Clinico-morphologic aspects of chronic mesotympanitis].
The present authors examined 84 patients with chronic mesotympanitis, 72 of which showed pathological lesions of the middle ear mucosa and bone. This was confirmed by X-ray contrasting examination before surgery and histological examination of tissue samples. Histological analysis showed that the level of destructive changes in middle ear cavities depended on the disease duration. Fibrous tissues of varying degree of maturity, cholesteatoma, tympanosclerotic patches, encapsulated fragments of caries bone frequently cause blockade of the aditus which complicates the chronic process in middle ear cavities and should be regarded as an absolute indication for surgical treatment of chronic mesotympanitis.


Relationship between invasiveness of pituitary somatotrophinomas and structural abnormalities of protein kinase C gene in human.
The potential role of the protein kinase C (PKC) transduction system in controlling proliferation of human pituitary somatotrophinomas was investigated. Twenty somatotrophinomas were studied using PCR and direct sequencing methods. No point mutation within the alpha PKC gene, previously thought to be associated with invasive pituitary tumors, was found in any of the 20 somatotrophinomas. It is concluded that PKC transduction system may play an important role in controlling pituitary somatotrophinoma proliferation, but there is no correlation between invasiveness and the previously reported alpha PKC gene mutation.


Active lighting applied to three-dimensional reconstruction of specular metallic surfaces by polarization imaging.
In the field of industrial vision, the three-dimensional inspection of highly reflective metallic objects is still a delicate task. We deal with a new automated three-dimensional inspection system based on polarization analysis. We first present an extension of the shape-from-polarization method for dielectric surfaces to metallic surfaces. Then, we describe what we believe to be a new way of solving the ambiguity concerning the normal orientation with an active lighting system. Finally, applications to shape-defect detection are discussed, and the efficiency of the system to discriminate defects on specular metallic objects made by stamping and polishing is presented.


Low-density lipoprotein receptor structure and folding.
The endoplasmic reticulum (ER) is a major cellular 'production factory' for many membrane and soluble proteins. A quality control system ensures that only correctly folded and assembled proteins leave the compartment. The low-density lipoprotein receptor (LDLR) is the prototype of a large family of structurally homologous cell surface receptors, which fold in the ER and function as endocytic and signaling receptors in a wide variety of cellular processes. Patients with familial hypercholesterolemia carry single or multiple mutations in their LDLR, which leads to malfunction of the protein, in most patients through misfolding of the receptor. As a result, clearance of cholesterol-rich LDL particles from the circulation decreases, and the elevated blood cholesterol levels cause early onset of atherosclerosis and an increased risk of cardiac disease in these patients. In this review, we will elaborate on the structural aspects of the LDLR and its folding pathway and compare it to other LDLR family members.


Role of antiplatelet agents in the primary and secondary prevention of atherothrombotic events in high risk-patients.
Atherothrombosis describes the superimposition of a thrombus on a ruptured atherosclerotic plaque, and is the primary cause of acute ischemic events. Atherothrombosis is a generalized and progressive process with an inflammatory component. Patients with disease in one vascular bed are at risk of disease in another, a concept known as "cross-risk." Platelet adhesion, activation, and aggregation in the final stage of atherothrombosis are ultimately responsible for arterial occlusion and consequent ischemia. Therefore, antiplatelet therapy is an effective treatment choice for secondary prevention. Clopidogrel, an adenosine diphosphate receptor antagonist, given alone or in combination with aspirin, may benefit secondary prevention of ischemic events. Current treatment guidelines suggest the use of a combination of these two agents for secondary prevention where appropriate. However, data conflict regarding the efficacy of antiplatelet therapy for primary prevention. A recent meta-analysis demonstrated that aspirin significantly reduces the risk of first myocardial infarction in both men and women. The recent Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance trial, which evaluated the effects of clopidogrel plus aspirin compared with aspirin alone, seems to support the use of dual antiplatelet therapy in secondary prevention, but suggests that it may not be more effective than aspirin alone in primary prevention.


An improved method for the measurement of rat tissue kallikrein using a monoclonal antibody which recognizes only active enzyme.
We have used a monoclonal antibody which recognizes active kallikrein to develop a method for measurement of inactive and active kallikrein in rat urine. The inactive kallikrein levels were calculated from the difference between values before and after trypsin pretreatment in the kallikrein direct radioimmunoassay. In this assay, the final dilution of ascitic fluid containing monoclonal antibody was 1:1.6 X 10(7) which gave 35% specific binding to 125I-labelled kallikrein, and the minimal detectable amount was 0.08 ng/tube. When inactive kallikrein was assessed by this method and a kininogenase assay in 23 randomly collected urines, a significant correlation was observed between the values obtained from the two assays (p less than 0.01). The regression line for this relation was similar to that observed between purified active kallikrein concentration and kininogenase activity. The active and inactive kallikrein excretion rates and the inactive/total kallikrein ratio in rats on normal sodium diet were 74.0 +/- 17.3 micrograms/day (m +/- SD), 82.8 +/- 14.4 micrograms/day and 53.1 +/- 7.1%, respectively. This method can now be applied to studies of prokallikrein activation.


Nephrectomy in renal carcinoma with distant metastasis.
A total of 96 cases of renal carcinoma with distant metastasis at the time of diagnosis was studied. The patients were classified into 4 groups: Group O (16) in whom nephrectomy was not performed, Group A (51) who died due to carcinoma within 1 year of nephrectomy, Group B (25) who died due to carcinoma 1 to 3 years after nephrectomy, and Group C (4) who survived for 3 years or more after nephrectomy. Six clinical measurements were evaluated: haemoglobin, ESR, alpha 2 globulin, temperature, weight and C reactive protein. In addition, performance status, the number of organs with metastases, number of metastatic lesions and tumour growth rate were measured. The results showed that in patients surviving for 1 year or more after nephrectomy, there was an abnormality in the results of 3 or less of the 6 clinical measurements, performance was 0 or 1, and the carcinoma had metastasised to only one organ. In addition, it was found that the growth of metastatic lesions in patients who survived for 3 years or more was much slower than in the other patients. Nephrectomy was found to be effective in only 27% of our cases and we consider that careful deliberation should be made pre-operatively as to whether nephrectomy is really necessary in patients with metastasis. The decision should be made on the basis of the results obtained in the 6 clinical measurements given above.


Key-Vertebral Screws Strategy for Main Thoracic Curve Correction in Patients With Adolescent Idiopathic Scoliosis.
The following study was a prospective radiographic and retrospective clinical data assessment of adolescent idiopathic scoliosis (AIS) patients who had undergone a key-vertebral screws strategy (KVSS) at a single institution, with a minimum of 2 years' follow-up. The aim of the study was to introduce the KVSS for the operative treatment of AIS of the main thoracic curve, and to address the role of the fulcrum-bending radiograph (FBR) in predicting the outcome of surgical management by this method. The application of multilevel pedicle screws for the main thoracic curve in AIS patients is popular in an effort to provide spinal stability, enhance fusion outcome, and provide optimal curve correction. However, with the application of pedicle screw also comes a potential risk for soft tissue and neural injury and increased health care costs. It remains unknown whether limited screw placement can provide proper curve correction without compromising patient outcome. A total of 17 consecutive patients with AIS extending to the main thoracic spine, who had undergone posterior fusion and fixation by the KVSS, a procedure in which screws are placed at important strategic points in the spine (ie, bilaterally at the upper and lower end segments of the fusion block, apical vertebra on the convex side, adjacent cephalad, and caudal screw placement on the concave side), at a single institution, with a minimum of 2 year' follow-up, were included. The assessment of preoperative standing posteroanterior and sagittal, FBR, and postoperative standing posteroanterior and sagittal plain radiographs were assessed in all patients. The flexibility of the curve as well as the fulcrum-bending correction index (FBCI) were calculated for all patients. Postoperatively, radiographs were assessed at the immediate (ie, 1 wk) and last follow-up. Clinical assessment entailed evaluation of patient demographics and the presence of any intraoperative or postoperative complications. The mean age at the time of surgery was 15.6 years. The mean follow-up was 39.8 months. The average FBR flexibility was 62.2%. The mean immediate curve correction was 71.2%, which did not differ in comparison with the last follow-up assessment (P>0.05). The mean immediate and last follow-up FBCIs were 119.3% and 112.5%, respectively (P=0.079). A significant negative correlation was found between immediate FBCI to that of the FBR curve flexibility (r=-0.706; P=0.002), which remained similar on the last follow-up (r=-0.681; P=0.003). Sagittal alignment did not significantly change from the immediate to last follow-up (P=0.163) Fusion was achieved in all patients. No instrumentation-related complications were noted. Key-vertebral screws strategy is a safe and cost-effective method for the surgical treatment of the main thoracic curve in AIS patients. Moreover, in the context of this strategy, the FBR may have some predictive utility in the correction of the main thoracic curve in AIS patients.


[Pharmacology of spinal facilitation: the basis for preventive analgesia].
Repeated C fiber stimulation results in increased spinal afferent processing leading to exaggerated response to a painful stimulus (hyperalgesia) and anomalous pain behavior in response to an otherwise innocuous stimulus (allodynia). Evidence points to a complex scenario in which continued C fiber stimulation leads to local spinal release of glutamate, which activates spinal N-methyl-D-aspartate receptors. Their activation then leads to increased intracellular Ca and later to spinal formation of several intermediaries, including prostanoids and nitric oxide. Both serve to facilitate spinal processing directly, by increasing the release of spinal neurotransmitters. Conversely, spinal delivery of antagonists of such processes prevents a hyperalgesixc state from developing. These observations are clearly relevant to the study and management of pain following injury in humans.


Quantitation of metal cations bound to membranes and extracted lipopolysaccharide of Escherichia coli.
Inductively coupled plasma emission spectroscopy was used to quantitate the metal cations bound to outer and cytoplasmic membranes and to extracted lipopolysaccharide from several Escherichia coli K12 strains. The outer membrane was found to be enriched in both calcium and magnesium relative to the cytoplasmic membrane. Both membranes contained significant levels of iron, aluminum, and zinc. The multivalent cation content of the lipopolysaccharide resembled that of the intact outer membrane. Lipopolysaccharide extracted from wild-type k12 strains contained higher levels of Mg than Ca regardless of the growth medium, but the medium used for growth did affect the relative amounts of bound Mg as well as the levels of the minor cations iron, aluminum, and zinc. In contrast, lipopolysaccharide isolated from a deep rough mutant strain, D21f2, contained more Ca than Mg. Electrodialysis of lipopolysaccharide from wild-type k12 strains removed 1 mol of Mg per mol of lipopolysaccharide but did not significantly affect the level of other bound metal ions. Dialysis of lipopolysaccharide against sodium (ethylenedinitrilo)tetraacetate removed most of the Mg and Ca, resulting in a sodium salt. The equimolar replacement of divalent cations with sodium in the sodium salt resulted in a net loss of counterion change. The sodium salt was dialyzed against either tris(hydroxymethyl)aminomethane hydrochloride, CaCl2, MgCl2, or TbCl3, and the resulting lipopolysaccharide salts were analyzed for their ionic composition. It was shown that tris(hydroxymethyl)aminomethane and Ca can replace some but not all of the Na bound to the sodium salt, but all of the other multivalent cations tested replaced Na, resulting in uniform lipopolysaccharide salts. Lipopolysaccharide isolated from the deep rough mutant strain D21f2 was also converted into a sodium salt. Relative to the wild-type lipopolysaccharide, Na was able to neutralize the anionic charge to a greater extent in the mutant lipopolysaccharide. Our results suggest that the loss of specific groups in the core region of the lipopolysaccharide from the mutant strain results in a more open structure that allows the binding of larger cations and of more monovalent cations.


Heat shock protein 90 acts in brassinosteroid signaling through interaction with BES1/BZR1 transcription factor.
Brassinosteroids (BRs), a class of phytohormones, control various physiological and developmental processes in plants. Two highly homologous transcription factors, brassinosteroid insensitive 1-EMS-SUPRESSOR 1 (BES1) and brassinazole resistant 1 (BZR1), act downstream of BR signaling to control several thousands of putative target genes. We reported previously that BES1 forms a complex with a molecular chaperone: heat shock protein 90 (HSP90). This study demonstrates that the amino-terminal and central parts of BES1 are responsible for its physical interaction with HSP90.3 in vitro. Additionally, we present evidence that BZR1 is a novel HSP90 partner aside from two BR signaling components previously identified as its clients: BES1 and brassinosteroid insensitive 2 (BIN2). Furthermore, geldanamycin, an inhibitor of ATPase activity in HSP90, caused BES1 hyperphosphorylation and disrupted the expression of BR-responsive genes. Considered together, our results imply that HSP90 takes a part in BR-mediated gene expression through complex formation with two major transcription factors.


[Association between DLST gene polymorphism and Alzheimer's disease].
To investigate the association between the polymorphic alleles of dihydrolipoamide succinyltransferase (DLST) gene cDNA at position A19117G in intron 13 and C19183T in exon 14 and the risk for sporandic Alzheimer's disease (SAD). The polymorphism of DLST gene was detected using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) techniques in 105 patients with sporadic Alzheimer disease and 109 normal controls. The frequency of AT/AC genotype was found to be significantly higher in SAD patients (21%) than in controls (10%) with an odds ratio of 2.36 (P < 0.05). The frequencies of AC/AC, AT/AT genotypes and AC allele were slightly decreased in cases with SAD as compared with controls. While the frequencies of the GC/GC genotype and GC allele were slightly higher in SAD patients than in controls. However, these differences were not statistically significant (P > 0.05). The AT/AC genotype of DLST gene is associated with an increased risk for SAD.


The expert witness: defending the profession or prosecuting your peers.
The use of CRNAs as expert witnesses in court cases is well-established. The CRNA who acts as a legal consultant or an expert witness is not retained merely to pontificate in the courtroom based on their considerable experience and expertise. The CRNA will undertake many roles in the process of assisting the attorney including those of (1) record reviewer and data analyst, (2) researcher and retriever, (3) synthesizer, and (4) teacher. Beyond these roles is the philosophical premise that the person best suited to evaluate the competence of a nurse anesthetist is another nurse anesthetist. Poor practitioners who are a danger to the public ought to be held accountable for their failings, whereas excellent practitioners who are mistakenly accused of negligence ought to be defended. Although challenging and time consuming, the role of the legal consultant and expert witness is rewarding in both financial and personal satisfaction terms. The role and functions of the CRNA who takes on the challenges of appearing as an expert witness or legal consultant is explored. The fine points of medical malpractice is not discussed, except as a cursory overview. The goal is to provide the practicing CRNA with the basic tools needed for these roles.


Effects of compounds from Garcinia mangostana on inflammatory mediators in RAW264.7 macrophage cells.
The fruit hull of Garcinia mangostana Linn. has been used in Thai traditional medicine for treatment of abscess and skin infection. The mangosteen fruit hull and its compounds were carried out to investigate for anti-inflammatory activity. The extract of Garcinia mangostana together with alpha- and gamma-mangostins were tested for anti-inflammatory effect against lipopolysaccharide (LPS)-induced nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-alpha) and interleukin-4 (IL-4) releases as well as their mechanisms in transcriptional levels using RAW264.7 macrophage cells. Mangosteen extract possessed potent NO inhibitory effect with an IC50 value of 1.0 microg/ml. The isolated compounds from the extract including alpha-mangostin and gamma-mangostin, possessed marked inhibitory effect against NO release with IC50 values of 3.1 and 6.0 microM, respectively. The extract exhibited potent inhibitory effect on PGE2 release (IC50=6.0 microg/ml), whereas those of alpha- and gamma-mangostins were 13.9 and 13.5 microM, respectively. However, mangostins possessed only moderate effects towards TNF-alpha and IL-4 releases with IC50 values ranging from 31.8 to 64.8 microM. Both extract and alpha-mangostin suppressed transcription of gene encoding inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in dose-dependent manners, whereas gamma-mangostin had only an inhibitory effect on transcription of iNOS. The present study may support the Thai traditional use of Garcinia mangostana fruit hull for treatment of inflammatory-related diseases through the inhibition of NO and PGE2 releases, but moderate effect through TNF-alpha and IL-4.


Modulation of DMBA-induced biochemical changes by organoselenium compounds in blood of rats.
The protective role of two synthetic organoselenium compounds 1-isopropyl-3-methylbenzimidazole-2-selenone (SeI) and 1, 3-di-p-methoxybenzylpyrimidine-2-selenone (Sell) was examined against the 7,12-dimethylbenz[a]anthracene (DMBA)-induced changes in biochemical parameters in blood of rats. Albino Winstar rats (150-200 g body wt) were treated with single dose of DMBA (50 mg/kg body wt) and organoselenium compounds (25 micromol/kg) for 4 weeks at two days internal. Blood was taken from the anaesthetized rats ventricle from their hearts for biochemical analysis. Administration of DMBA resulted in elevation of urea, uric acid and creatinine levels as well as AST, ALT and LDH activities and decrease in levels of total proteins, albumin and globulin. SeI and SeII caused a significant (p<0.05) decrease in urea, uric acid and creatinine levels and alanine aminotransferase (ALT); aspartate aminotransferase; (AST) and lactate dehydrogenase (LDH) activities and significantly increased the levels of total protein and albumin (p<0.05). These organoselenium compounds are likely to be beneficial in human health.


Eater: a big bite into phagocytosis.
The phagocytosis of invading microorganisms by specialized blood cells is a crucial element of innate immunity in both mammals and insects. In this issue of Cell, Kocks et al. (2005) demonstrate that Eater, a scavenger receptor, plays an important role in the recognition and phagocytosis of bacteria in the fruit fly Drosophila.


Gastric electrical activity and gastric emptying in term and preterm newborns.
The aims of this study were to evaluate the gastric electrical activity and gastric emptying in preterm and term newborns and to assess the development of gastric motility by comparing newborns of different gestational ages. The cutaneous electrogastrography and the ultrasonographic study of the gastric emptying were performed before and after milk formula in three groups of infants: 12 preterm newborns with a gestational age of 28-32 weeks, 11 preterm newborns with a gestational age of 32-36 weeks, and 10 full-term newborns with a gestational age of 36-40 weeks. All recording sessions were performed 1 week after infants had reached full enteral feeding. The percentage of normal slow waves was similar in the three groups but it was not predominant compared to tachygastria in the earliest premature infants (59.3% (12.7-92.3) vs. 29.6% (3.7-78.8); P < 0.05). In addition, a progressive increase in the normal slow wave percentage (59.3% (17.4-87.4), 60.9% (38.1-89.7), 77.8% (66.4-84.8); P < 0.05) was observed as gestation advanced. As regards gastric emptying parameters, the antral area was greater and T(1/2) was longer in the preterm newborns of 28-32 weeks than preterm newborns of 32-36 weeks and full-term newborns (fasting antral area: 0.96 cm2 (0.6-1.5), 0.63 cm2 (0.4-1.2), 0.55 cm2 (0.1-0.9) respectively, P < 0.05; T(1/2): 83.4 min (76.0-108.5), 70 min (57.5-89.5) and 71.8 min (54.9-81.2), respectively P < 0.05). The comparisons of gastric emptying curves made among the three groups showed a reduced antral dilatation in preterm newborns of 28-32 weeks compared to full-term newborns at 30 and 60 min after a meal. In conclusion, although enteral feeding is important for the development process of gastrointestinal motility, gastric electrical activity and gastric emptying show an intrinsic maturation depending on the gestational age.


microGISAXS and protein nanotemplate crystallization: methods and instrumentation.
Microbeam grazing-incidence small-angle X-ray scattering (microGISAXS) has been used and the technique has been improved in order to investigate protein nucleation and crystal growth, assisted by a protein nanotemplate. The aim is to understand the protein nanotemplate method in detail, as this method has been proved capable of accelerating and increasing crystal size and quality as well as inducing crystallization of proteins that are not crystallizable by classical methods. The nanotemplate experimental setup was used for drops containing growing lysozyme crystals at three different stages of growth.


[A case of amyotrophic lateral sclerosis presenting as motor aphasia in its early stage].
A 76-year-old right-handed woman complained of speech disturbance and difficulity of singing was admitted to our hospital. Examination showed motor aphasia and mild cognitive impairment. After she was discharged, dementia and weakness of the extremities had rapidly progressed. She was readmitted eight month after the first visit, when she was almost abulic, her skeletal and bulbar muscles were remarkably atrophic, and hyperreflexia of the extremities were seen. Electromyographcal study showed neurogenic pattern. These findings suggest amyotrophic lateral sclerosis (ALS) with dementia. Pathological findings were atrophy at the anterior horn of the spinal cord. The brain was diffusely atrophic. The extent of degenerative change was not lateralized. This case is a discriminative type of ALS with dementia, that its first symptom is motor aphasia.


Waterproof paper as a new substrate to construct a disposable sensor for the electrochemical determination of paracetamol and melatonin.
Disposable electrochemical sensors using sustainable and cheap materials are an exciting alternative to produce new kinds of sensing platforms. Waterproof paper (WP) is a biodegradable and biocompatible material that allows dropped of the sample on its surface without absorption by fibers. Also, WP can be used for miniaturized sensors construction. In this work, a conductive ink was produced with nail polish and graphite powder, using the WP as the sensor substrate for paracetamol (PAR) and melatonin (MEL) voltammetric determination. PAR is a pharmaceutical commonly used in high doses for the relief of pain and fever, and MEL is a hormone related to several diseases besides a direct relation to sleep quality. Using differential pulse voltammetry for PAR determination, the WP sensor showed a linear response in the concentration ranging from 0.50 μmol L-1 to 100 μmol L-1 with a limit of detection (LOD) of 53.6 nmol L-1. Square wave voltammetry was applied for MEL determination, and the proposed electrode presented linear response ranging from 0.80 μmol L-1 to 100 μmol L-1 and LOD of 32.5 nmol L-1. The sensor showed excellent repeatability and reproducibility for consecutive measurements. Then, the disposable WP sensor was successfully applied in the determination of PAR and MEL in pharmaceutical and biological samples, with recovery values, above 91.1%. The described architecture allowed the manufacture of a disposable, simple, and low-cost electroanalytical device that can be used for electrochemical sensing.


Cathepsin B plays a critical role in inducing Alzheimer's disease-like phenotypes following chronic systemic exposure to lipopolysaccharide from Porphyromonas gingivalis in mice.
A number of clinical and experimental studies have revealed a strong association between periodontitis and accelerated cognitive decline in Alzheimer's disease (AD); however, the mechanism of the association is unknown. In the present study, we tested the hypothesis that cathepsin (Cat) B plays a critical role in the initiation of neuroinflammation and neural dysfunction following chronic systemic exposure to lipopolysaccharide from Porphyromonas gingivalis (PgLPS) in mice (1mg/kg, daily, intraperitoneally). Young (2months old) and middle-aged (12months old) wild-type (WT; C57BL/6N) or CatB-deficient (CatB-/-) mice were exposed to PgLPS daily for 5 consecutive weeks. The learning and memory function were assessed using the passive avoidance test, and the expression of amyloid precursor protein (APP), CatB, TLR2 and IL-1β was analyzed in brain tissues by immunohistochemistry and Western blotting. We found that chronic systemic exposure to PgLPS for five consecutive weeks induced learning and memory deficits with the intracellular accumulation of Aβ in neurons in the middle-aged WT mice, but not in young WT or middle-aged CatB-/- mice. PgLPS significantly increased the expression of CatB in both microglia and neurons in middle-aged WT mice, while increased expression of mature IL-1β and TLR2 was restricted to microglia in the hippocampus of middle-aged WT mice, but not in that of the middle-aged CatB-/- ones. In in vitro studies, PgLPS (1µg/ml) stimulation upregulated the mean mRNA expression of IL-1β, TLR2 and downregulated the protein levels of IκBα in the cultured MG6 microglia as well as in the primary microglia from WT mice, which were significantly inhibited by the CatB-specific inhibitor CA-074Me as well as by the primary microglia from CatB-/- mice. Furthermore, the mean mRNA expression of APP and CatB were significantly increased in the primary cultured hippocampal neurons after treatment with conditioned medium from PgLPS-treated WT primary microglia, but not after treatment with conditioned medium neutralized with anti-IL-1beta, and not after treatment with conditioned medium from PgLPS-treated CatB-/- primary microglia or with PgLPS directly. Taken together, these findings indicate that chronic systemic exposure to PgLPS induces AD-like phenotypes, including microglia-mediated neuroinflammation, intracellular Aβ accumulation in neurons and impairment of the learning and memory functions in the middle-aged mice in a CatB-dependent manner. We propose that CatB may be a therapeutic target for preventing periodontitis-associated cognitive decline in AD.


Lingonberry Extract Provides Neuroprotection by Regulating the Purinergic System and Reducing Oxidative Stress in Diabetic Rats.
Beneficial effects produced by polyphenolic compounds are used in the treatment of various diseases, including diabetes. Thus it is relevant to investigate the protective effect of lingonberry extract (LB) on the activities of nucleoside triphosphate diphosphohydrolase (NTPDase), 5'-nucleotidase (5'-NT), and adenosine deaminase (ADA); the density of A1, A2A, and P2×7 receptors; production of reactive species (RS); and the levels of thiobarbituric acid reactive substances (TBARS) in the cerebral cortex of streptozotocin-induced diabetic rats. Animals were divided into five groups (n = 10): control/saline; control/LB 50 mg kg-1 ; diabetic/saline; diabetic/LB 25 mg kg-1 ; and diabetic/LB 50 mg kg-1 ; and treated for 30 days. Our results demonstrate that the treatment with LB increased NTPDase activity in the diabetic/LB 50 group compared to diabetic/saline group. Western blot analysis showed that LB restored the density of purinergic receptors to the approximate values of the control/saline group. An increase in the levels of RS and TBARS was observed in the diabetic/saline group compared with the control/saline group, and treatment with LB can prevent this increase. This study showed that LB could reverse the modifications found in the diabetic state, suggesting that lingonberry may be a coadjuvant in the treatment of diabetes.


Oxidants and iron in chronic kidney disease.
Oxidants derived either from leukocytes in proliferative glomerular nephritis or from resident glomerular cells in nonproliferative glomerulonephritis have been shown to have several biologic effects relevant to chronic kidney disease. These include: the ability of oxidants to damage glomerular basement membrane (GBM) and to directly induce proteinuria; effects that would lead to a fall in the glomerular filtration rate; and effects that would account for the morphologic changes observed in chronic kidney disease. In experimental models the role of oxidants has been demonstrated in both proliferative glomerulonephritis (e.g., anti-GBM antibody disease) as well as experimental models of minimal change disease and membranous nephropathy. Oxidants have also been shown to be an important mediator of the various pathways that have been implicated in diabetic nephropathy. Antioxidants and iron chelators have also been shown to retard functional and morphologic changes observed in progressive kidney disease. Taken together, these experimental studies suggest an important role of oxidants in chronic kidney disease.


You are better off running than walking revisited: Does an acute vestibular imbalance affect muscle synergies?
It has been suggested that vestibular cues are inhibited for the benefit of spinal locomotor centres in parallel with the increase in locomotion speed. This study aimed at quantifying the influence of a transient vestibular tone imbalance (TVTI) on gait kinematics, muscle activity and muscle synergies during walking and running. Twelve participants walk or run at a self-selected speed with or without TVTI, which was generated by 10 body rotations just prior the locomotion task. Three-dimensional lower-limb kinematic was recorded simultaneously with the surface electromyographic (EMG) activity of 8 muscles to extract muscle synergies via non-negative matrix factorization. Under TVTI, there was an increased gait deviation in walking compared to running (22.8 ± 8.4° and 8.5 ± 3.6°, respectively; p < 0.01), while the number (n = 4) and the composition of the muscle synergies did not differ across conditions (p = 0.78). A higher increase (p < 0.05) in EMG activity due to TVTI was found during walking compared to running, especially during stance. These findings confirmed that the central nervous system inhibited misleading vestibular signals according to the increase in locomotion speed for the benefit of spinal mechanisms, expressed by the muscle synergies.


Air-stable all-inorganic nanocrystal solar cells processed from solution.
We introduce an ultrathin donor-acceptor solar cell composed entirely of inorganic nanocrystals spin-cast from solution. These devices are stable in air, and post-fabrication processing allows for power conversion efficiencies approaching 3% in initial tests. This demonstration elucidates a class of photovoltaic devices with potential for stable, low-cost power generation.


Suppression of B16 melanoma lung colonization by syngeneic monoclonal antibodies.
Syngeneic monoclonal antibodies (MAbs) were produced to B16 melanoma by hybridization of spleen cells from B16-F1 or B16-F10 tumor-bearing C57BL/6J mice. Two antigens were identified by the immunofluorescence reactions of anti-F1 MAbs, 2G10 (IgG1) and 3C10 (IgM). Both antigens are membrane associated in 97-99% of fixed F1 and F10 cells and are cross-reactive with normal syngeneic thymocytes, and other normal and transformed cultured mouse cells. An anti-F10 Mab, 3E9 (IgG3), reacts with a membrane antigen found in about 40% of F1 and F10 cells and in all transformed mouse cells tested, but was not found in normal cells. The 3C10 and 3E9 antigens are shed into the medium of cultured cells. 125I-Labeled membrane components of Mr 48,000 and 40,000 (3C10) and 25,000 (3E9) were immunoprecipitated. Some 3C10 immunoprecipitates also contained components of Mr 25,000 and 15,000. The three MAbs were tested for suppression of lung colonization by B16-F1 and B16-F10 metastatic variants in C57BL/6J mice. MAbs were injected 1 day prior to and 1 week after injection of tumor cells. 2G10 was highly suppressive for both B16-F1 and B16-F10 cells. 3C10 and 3E9 were suppressive for B16-F10 cells but were nonsuppressive and enhancing for B16-F1 cells (P less than or equal to 0.05). A novel immunotherapy model was tested. Delayed hypersensitivity was selectively induced to the 3C10 MAb in C57BL/6J mice by sensitization with lipid-conjugated purified MAb. Sensitized mice were injected with B16 cells and MAb to determine whether a cellular reaction with cell bound MAb in vivo could be suppressive for tumor cells. The treatment was suppressive for B16-F1 lung colonies, but caused augmentation of lung colonies from B16-F10 cells (P less than or equal to 0.05).


Rating scale for psychogenic nonepileptic seizures: scale development and clinimetric testing.
Our aim was to develop a clinimetric scale evaluating motor phenomena, associated features, and severity of psychogenic nonepileptic seizures (PNES). Sixty video/EEG-recorded PNES induced by suggestion maneuvers were evaluated. We examined the relationship between results from this scale and results from the Clinical Global Impression (CGI) scale to validate this technique. Interrater reliabilities of the PNES scale for three raters were analyzed using the AC1 statistic, Kendall's coefficient of concordance (KCC), and intraclass correlation coefficients (ICCs). The relationship between the CGI and PNES scales was evaluated with Spearman correlations. The AC1 statistic demonstrated good interrater reliability for each phenomenon analyzed (tremor/oscillation, tonic; clonic/jerking, hypermotor/agitation, atonic/akinetic, automatisms, associated features). KCC and the ICC showed moderate interrater agreement for phenomenology, associated phenomena, and total PNES scores. Spearman's correlation of mean CGI score with mean total PNES score was 0.69 (P<0.001). The scale described here accurately evaluates the phenomenology of PNES and could be used to assess and compare subgroups of patients with PNES.


Relationship between clustering of post-ovulatory and hierarchical follicles and their order of ovulation in the mature domestic hen (Gallus gallus domesticus).
Hierarchical (> 8 mm) and post-ovulatory follicles from the ovaries of laying hens at 45 and 86 weeks of age were assigned to clusters defined by the coalescence of their follicular stalks. They were also classified by size to give the succession in which ovulation had occurred, or would occur for the hierarchical follicles. The association between the order of ovulation and the observed clusters was compared with randomness and with dependence on the cluster in which the immediately preceding ovulation occurred. The order of ovulation was associated randomly with clusters, and was independent of the cluster containing the preceding ovulation. Many perceived clusters of successive follicles and post-ovulatory follicles may be compatible with a random order of ovulation. These findings do not support theories of stimulation or inhibition of adjacent follicles, leading to eventual ovulation, by a dominant follicle.


Serum calcium in normal pregnant women.
A prospective case-control study was done to determine any difference of serum calcium levels in pregnant women in third trimester and non-pregnant women. Serum calcium levels were determined in 30 normal non-gravid women and 30 women with normal pregnancies during third trimester with age range of 17-35 years. The mean serum calcium levels were found to be significantly lower in normal pregnant woman in third trimester than that of normal non-pregnant controls.


Electron-microscopic study of systemic myonecrosis due to poisoning by tropical rattlesnake (Crotalus durissus terrificus) in humans.
This article describes the ultrastructural study of skeletal muscle biopsy specimens from five patients following envenomization by tropical rattlesnake (Crotalus durissus terrificus). All the patients were bitten in the leg and the biopsy specimens were obtained from the contralateral gastrocnemius muscle in the middle of the lower leg. A wide spectrum of detailed ultrastructural changes involving muscle fibers and microvasculature was demonstrated. Essentially, such lesions included widespread necrotic myofibers intermixed with intact fibers, accompanied by changes in the endothelial lining of the intramuscular blood capillaries and small arterial vessels, reducing their lumens. Since these alterations were observed in biopsy specimens from the limb contralateral to the site of the bite, they clearly demonstrate the systemic myonecrotic action of the venom of a tropical rattlesnake. On the basis of these data, the mechanism of venom-induced myopathy is described. It is postulated that the pathogenesis of systemic myonecrosis due to poisoning by C durissus terrificus is a complex one, probably due to direct damage to cells by the myotoxins of the venom, as well as indirect effects due to ischemia.


[Thalidomide: new perspectives for its use as antiinflammatory, immunossupressive and antiangiogenic drug].
The new uses of thalidomide are reviewed. It has recently been used as antinflammatory, immunosuppressive, antiangiogenic, and antiviral agent. Although its mechanism of action is not yet understood, the advantage of its use in several diseases, such as erythema nodosum leprosum, multiple myeloma, and graft-versus-host-disease is evident. Owing to its teratogenic properties, the use of thalidomide must be very well controlled. However, thalidomide has become a very important alternative, with new applications being studied.


Recombinant glycoprotein 120 of human immunodeficiency virus is a potent interferon inducer.
Cells infected with human immunodeficiency virus (HIV) induce antiviral activity in peripheral blood mononuclear cells (PBMC) from healthy donors. This activity is neutralized by anti-interferon-alpha antibody and partially destroyed at pH 2. Previous studies with enriched cell populations and monoclonal antibodies suggest that B lymphocytes are the main IFN-producing cells, and that both CD4 and HLA class II antigens are essential for IFN induction. Since the initial event of HIV infection of CD4+ cells is the interaction of the virus coat glycoprotein gp120 with CD4 molecule, we investigated whether gp120 is responsible for IFN induction. Using PBMC and recombinant gp120 obtained from a baculovirus expression system, dose-dependent induction of antiviral activity was observed with titers approaching 10(3) IU/ml. This induction was blocked in the presence of antibody to gp120. The antiviral activity was characterized as IFN-alpha by neutralization with IFN alpha-specific antibody. Preincubation of PBMC with anti-CD4 or the presence of soluble CD4 during incubation inhibited IFN induction, indicating that interaction of gp120 with cell-associated CD4 is responsible for this induction. Neither lymphoproliferation nor interleukin-2 (IL-2) production was observed during IFN induction. However, class G immunoglobulin secretion was enhanced by gp120, indicating that B cells are direct or indirect targets of gp120 stimulation in this experimental system. Since gp120 is shed from HIV-infected cells and occurs in the serum of acquired immunodeficiency syndrome (AIDS) patients, our data suggest that this glycoprotein is responsible for the induction of endogenous IFN and the polyclonal activation of B cells both of which are observed in AIDS patients.


Chronic exposure to lidocaine does not alter flux through sodium channels in cultured neuronal cells.
Although tachyphylaxis to local anesthetics has been reported in the clinical literature for more than two decades, the molecular mechanism(s) remain unknown. The authors described an attempt to create an in vitro model for tachyphylaxis to local anesthetics using cultured neuronal cells. Murine neuroblastoma cells (N1E115) and rat pheochromocytoma cells (PC-12) were grown in the presence or absence of lidocaine or tetrodotoxin for between 1 and 14 days. Thereafter, the authors tested flux through sodium channels by measuring total and tetrodotoxin-sensitive flux of 14C-labeled guanidinium (a ligand for the sodium channel) into the cells using the technique of Jacques et al. Chronic lidocaine or tetrodotoxin treatment caused no change relative to control cells in total or tetrodotoxin-sensitive guanidinium flux, or in the subsequent ability of lidocaine in the flux assay mixture to inhibit guanidinium flux. The authors concluded that chronic lidocaine or tetrodotoxin application did not produce changes in stimulated sodium channel activity or subsequent lidocaine susceptibility in this model. To the extent that this model simulated the clinical situation, mechanisms other than up-regulation of sodium channel number or maximal stimulated flux per channel may have been responsible for producing tachyphylaxis.


Enzymatic method for determination of the degree of deacetylation of chitosan.
A new method was developed for the accurate determination of the degree of deacetylation of chitosan. The method involves the complete hydrolysis of chitosan to glucosamine and N-acetylglucosamine by a cooperative action of chitosanolytic enzymes exo-beta-D-glucosaminidase, beta-N-acetylhexosaminidase, and chitosanase, and subsequent determination of the monosaccharides by specific colorimetric assays or HPLC. The conditions required for the complete hydrolysis of chitosan were examined and the degree of deacetylation of several chitosan samples was determined.


Countdown to 2015: assessment of donor assistance to maternal, newborn, and child health between 2003 and 2006.
To track donor assistance to maternal, newborn, and child health-related activities is necessary to assess progress towards Millennium Development Goals 4 and 5 and to foster donor accountability. Our aim was to analyse aid flows to maternal, newborn, and child health for 2005 and 2006 and trends between 2003 and 2006. We analysed and coded the complete aid activities database for 2005 and 2006 with methods that we developed previously to track official development assistance. For the 68 Countdown priority countries, we report two indicators for use in monitoring donor disbursements: official development assistance to child health per child and official development assistance to maternal and neonatal health per livebirth. Donor disbursements increased from US$2119 million in 2003 to $3482 million in 2006; funding for child health increased by 63% and that for maternal and newborn health increased by 66%. In the 68 priority countries, child-related disbursements increased from a mean of $4 per child in 2003 to $7 per child in 2006; disbursements for maternal and neonatal health increased from $7 per livebirth in 2003 to $12 per livebirth in 2006. Nonetheless, disbursements fell in some countries. After adjustment for other determinants, countries with higher under-5 mortality received more official development assistance per child, but official development assistance to maternal and newborn health did not seem to be well targeted towards countries with the greatest maternal health needs. Donor resource tracking should be continued to help hold donors accountable and encourage targeting of resources to countries with greatest needs.


Tooth in an ovarian cystic teratoma.
The findings of this analysis indicate that the hard tissue is a decidous canine with a small amount of alveolar bone.


Aneurysm of the radial artery following blunt trauma to the wrist.
Aneurysms involving the distal radial artery are rare lesions which are usually secondary to penetrating trauma or iatrogenic injury. Blunt trauma is an extremely uncommon cause. In the absence of a history of penetrating vascular injury, a radial artery aneurysm may easily be misdiagnosed as a nonvascular mass such as a synovial cyst. A diagnostic approach to these lesions is discussed emphasizing the role of noninvasive studies in uncomplicated cases. Excision of the aneurysm is recommended. The decision to ligate or reconstruct the radial artery remains controversial.


Prevalence and correlates of non-optimal secondary medical prevention in patients with stable coronary artery disease.
In patients with coronary artery disease (CAD), non-optimal use of evidence-based medications is associated with an increased risk of adverse outcome. To assess the prevalence and correlates of non-optimal secondary medical prevention in patients with stable CAD. We included 4184 consecutive outpatients with stable CAD. Treatment at inclusion was classified as optimal/non-optimal regarding the four major classes of secondary prevention drugs: antithrombotics; statins; angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs); and beta-blockers. For each treatment, the prescription was considered non-optimal if the drug was missing despite a class IA indication according to international guidelines. To assess the information globally, non-optimal secondary prevention was defined as at least one major treatment missing. The proportions of patients with non-optimal treatment were 0.7%, 7.8%, 12.9% and 10.3% for antithrombotics, statins, ACE inhibitors/ARBs and beta-blockers, respectively. Non-optimal secondary medical prevention was observed in 16.8% of cases. By multivariable analysis, the correlates of non-optimal secondary medical prevention were long time interval since last coronary event (P<0.0001), older age (P<0.0001), diabetes mellitus (P<0.0001), hypertension (P<0.0001), no history of myocardial infarction (P=0.001), no history of coronary revascularization (P=0.013) and low glomerular filtration rate (P=0.042). Although most patients with stable CAD are receiving evidence-based medications according to guidelines, there remain subgroups at higher risk of non-optimal treatment. In particular, it might be feasible to improve prevention by focusing on patients in whom a long time has elapsed since the last coronary event.


Impact of forecasted changes in Polish economy (2015 and 2020) on nutrient emission into the river basins.
Poland, with its large drainage area, with 50% contribution of agricultural land and 45% contribution of population to overall agricultural land area and population number in the Baltic catchment, is the largest exporter of riverine nitrogen (N) and phosphorus (P) to the sea. The economic transition has resulted in substantial, statistically significant decline in N, P export from Polish territory to the Baltic Sea. Following the obligations arising from the Helsinki Commission (HELCOM) declarations, in the coming years, Poland is expected to reduce riverine N loads by ca. 25% and P loads by ca. 60% as referred to the average flow normalized loads recorded in 1997-2003. The aim of this paper is to estimate annual source apportioned N and P emissions into these river basins in 2015 and 2020 with application of modeling studies (MONERIS). Twelve scenarios, encompassing changes in anthropogenic (diffuse, point source) and natural pressure (precipitation, water outflow due to climate change), have been applied. Modeling outcome for the period 2003-2008 served as our reference material. In applied scenarios, N emission into the Oder basin in 2015 and 2020 shows an increase from 4.2% up to 9.1% as compared with the reference period. N emission into the Vistula basin is more variable and shows an increase by max. 17.8% or a decrease by max. 4.7%, depending on the scenario. The difference between N emission into the Oder and Vistula basins is related to the catchment peculiarities and handling of point sources emission. P emission into both basins shows identical scenario patters and a maximum decrease reaches 17.8% in the Oder and 16.7% in the Vistula basin. Despite a declining tendency in P loads in both rivers in all the scenarios, HELCOM targeted P load reduction is not feasible.


META. 1. A program for the evaluation of metabolic transformation of chemicals.
A new metabolism program, META, is introduced. In this paper, the basic principles on which the program operates are described. META is an expert system, capable of predicting the sites of potential enzymatic attack and the nature of the chemicals formed by such metabolic transformations. It operates from dictionaries of transformation operators, created by experts to represent known metabolic paths.


Extracellular ATP increases cytosolic calcium in cultured rat renal arterial smooth muscle cells.
1. Experiments were conducted on cultured renal arterial smooth muscle cells to determine the ability of extracellular ATP to alter cytosolic calcium concentration and to determine the mechanisms by which this effect occurs. 2. ATP (100 mumol/L) caused the fluorescence ratio of fura-2 to increase from a control value of 1.06 +/- 0.05 to 2.06 +/- 0.13 (P < 0.01) before stabilizing at a sustained level of 1.35 +/- 0.04 (n = 8; P < 0.05). 3. Removal of extracellular calcium from the bathing medium resulted in an attenuation of the initial response to 100 mumol/L ATP with cell fluorescence increasing from 1.16 +/- 0.18 to 1.44 +/- 0.18 ratio units (n = 5). Furthermore, the initial increase in fluorescence ratio rapidly declined to 1.02 +/- 0.06, indicating that an influx of extracellular calcium is required to sustain the increase in fura-2 fluorescence. 4. Depletion of intracellular calcium pools with thapsigargin prevented the increase in fura-2 fluorescence evoked by ATP. 5. These data suggest that ATP-mediated increases in cytosolic calcium in cultured renal arterial smooth muscle cells involve calcium release from the thapsigargin-sensitive, intracellular pool in conjunction with calcium influx from the extracellular medium.


Pericarditis with massive pericardial effusion: an unusual complication of primary biliary cirrhosis.
Primary Biliary Cirrhosis (PBC) is a debilitating autoimmune condition associated with a constellation of extrahepatic inflammatory manifestations accentuating its morbidity and mortality. Pericarditis and pericardial effusion had been rarely associated with and inadequately characterized in PBC. We present a challenging case of inflammatory pericarditis and life-threatening massive pericardial effusion in a 49 year old patient with PBC. This complication should be more recognized and appropriately treated to avoid progression to cardiac tamponade.


Safety in numbers.
An organisation with royal college status thinks long and hard before quantifying something as fundamental as safe staffing levels. This week the RCN launches its recommended skill-mix ratio for registered and non-registered staff on general wards in NHS acute trusts, a move that should be welcomed by everyone from patients to ministers. The two thirds registered, one third unregistered benchmark provides a reference point when calculating workforce demands. And there is no organisation better placed to set down this marker for nursing care than nurses' own royal college.


Decreased need of large joint replacement in patients with rheumatoid arthritis in a specialized Brazilian center.
Disease-modifying antirheumatic biological and non-biological therapies are associated with reduced disease progression and joint destruction. Suggestions have been made that total knee and hip joint arthroplasty indications are decreasing as a beneficial effect of the new forms of therapy for rheumatoid arthritis. We present findings of our institution on the incidence of joint arthroplasty in the past few years in patients with rheumatoid arthritis and the increase in the numbers of procedures not associated with inflammatory arthritis.


Prolonged fluorescence lifetime of carbon quantum dots by combining with hydroxyapatite nanorods for bio-applications.
Carbon quantum dots (CQDs) are a new type of fluorescent nanoparticle for cell imaging and tracking. However, they would easily diffuse and quench, followed by the loss of their fluorescence ability. By connecting their functional groups with other nanoparticles, the CQDs will be protected from destruction and exhibit long-time fluorescence. Here, carbon quantum dot-hydroxyapatite (CQD-HAp) hybrid nanorods were prepared by the self-assembly of CQDs on the surface of HAp nanorods through a facile one-pot process. The morphology and size of the CQD-HAp hybrid nanorods can be well controlled by using oleic acid, which meanwhile is the source of CQDs. The hydrophilic CQD-HAp hybrid nanorods have prolonged fluorescence life due to the connection between CQDs and HAp nanorods, and exhibit a higher fluorescence quantum yield than pure CQDs. In addition, when hybrid nanorods load doxorubicin (Dox) to form Dox-CQD-HAp hybrid nanorods, they can more efficiently kill human cervical cancer (HeLa) cells, rather than human prostatic cancer (PC-3) cells. Long time fluorescence for cell imaging and high efficiency in killing cancer cells as a drug-delivery medium make CQD-HAp hybrid nanorods have great potential applications in the bio-field.


[Phase plane (volume to volume-time function loop) display of the data from radionuclide ventriculography obtained by single cardiac probe system].
To assess the left ventricular (LV) performance more sensitively, a new display method of phase plane (PP), displaying volume and volume-time function (dV/dt) in a single image, was applied to radionuclide ventriculography obtained by a single cardiac probe system. In this PP loop, the width of the horizontal axis indicates relative LV volume, and the height of the vertical axis indicates dV/dt. The direction of the rotation of this loop is clockwise. We classified 160 patients with various heart diseases into seven groups, according to the configuration of the loop. And we proposed two new parameters, named peak S and peak D, from this PP display. We can easily detect the left atrial contribution (AC/SV) and its peak rate (peak AC), which are very sensitive parameters for detecting the left ventricular diastolic function abnormality. With these parameters, we can detect 105 patients (74.5%) with abnormal LV function out of 141 patients with various heart diseases. However, with conventional parameters (named EF, PER, PFR, 1/3 EF), we can detect only 80 patients (56.7%) with LV dysfunction. Therefore, we conclude that the single image PP display is a sensitive method for assessing the abnormality of the LV function, not only by evaluating the conventional parameters, but also by analyzing the configuration of the volume to volume-time function loop.


There is no 1954 in that core! Interpreting sedimentation rates and contaminant trends in marine sediment cores.
Marine sediment preserves a useful archive for contaminants and other properties that associate with particles. However, biomixing of sediments can smear the record on a scale of years to thousands of years, depending on sedimentation rate and on the depth and vigour of mixing within a particular sediment. Where such mixing occurs, dates can no longer be associated with discrete sediment depths. Nevertheless, much can still be learned from biomixed profiles, provided that mixing is accounted for. With no modelling at all, it is possible to calculate an inventory of a contaminant at a site and a maximum possible sedimentation rate, and to determine whether the contaminant has increased or decreased over time. Radiodating the core with (210)Pb permits the estimation of sedimentation and mixing rates, which can be combined with the surface contaminant concentration to estimate an approximate flux of the contaminant. Numerical models that incorporate sedimentation and mixing rates (determined using (210)Pb and other transient signals with known deposition histories) can provide the basis to propose plausible histories for contaminant fluxes.


Splenic abscess.
A review of autopsy files and clinical case reports demonstrates two categories of splenic abscess. First, the abscesses discovered at postmortem usually are multiple, small manifestations of widespread, lethal infection in immunologically crippled hosts. A clinical diagnosis seldom is made. Second, the splenic abscesses encountered by the clinician are usually solitary, large, and challenge his diagnostic skills. Recognition is of vital importance, for therapy can be highly successful. Left untreated, the mortality rate is very high. The features, clinical management, and pathogenesis of splenic abscesses are discussed.


The use of pencil lead as a matrix and calibrant for matrix-assisted laser desorption/ionisation.
Pencil lead is shown to be an effective matrix and calibrant in matrix-assisted laser desorption/ionisation (MALDI) mass spectrometry. Various groups of analytes, including peptides, polymers and actinide metals, can be readily ionised using MALDI when deposited onto a pencil lead matrix. The matrix is seen to have advantages in sample preparation relating to its hydrophobic properties and almost complete suppression of the matrix during analysis. Using pencil lead as a matrix is a quick and convenient method of qualitative analysis and has been shown to be quantitative for the isotope ratio analysis of actinide metals.


The unhappy obese child.
One of the most painful aspects of obesity may be the emotional suffering it causes. The paper discusses the psychological and social effects of obesity. Current studies examining the psychosocial strains of obese children and adolescents are reported. The report especially focuses on stigmatization, mental health disorders, school performance and health-related quality of life. Research is showing that obesity is associated with poorer psychosocial functioning even compared with other chronic diseases. Future studies should further explicate the risk and protective factors for developing severe psychosocial strain.


Acute klebsiella epiglottitis: considerations for initial antibiotic coverage.
Acute epiglottis due to Klebsiella pneumoniae in an adult patient is described. The patient failed to respond to ampicillin and required cephalosporin therapy as well as surgical drainage. In view of increased resistance of Hemophilus influenzae to ampicillin and because of other possible etiologic agents such as Staphylococcus aureus and non-Hemophilus gram-negative rods, consideration should be given for the initial use of one of the recently introduced cephalosporins such as moxalactam or cefamandole in the treatment of adult epiglottitis.


Catalytic asymmetric vinylogous Mannich-type (AVM) reaction of nonactivated α-angelica lactone.
A direct highly diastereo- and enantioselective asymmetric vinylogous Mannich-type (AVM) reaction of aldimines with nonactivated natural α-angelica lactone has been successfully developed. It was demonstrated that the nonactivated natural α-angelica lactone is a useful vinylogous nucleophile to give the chiral δ-amino γ,γ-disubstituted butenolide carbonyl derivatives. The N,N'-dioxide L2-Sc(III) complex is efficient toward the obtention of a range of corresponding products with adjacent quaternary and tertiary stereocenters in excellent dr and ee values.


Molecular predictors of efficacy of adjuvant weekly paclitaxel in early breast cancer.
Treatment with fluororacil, epirubicin, and cyclophosphamide followed by weekly paclitaxel (FEC-P) yielded superior disease-free survival than FEC in the adjuvant breast cancer trial GEICAM 9906. We evaluate molecular subtypes predictive of prognosis and paclitaxel response in this trial. Two molecular subtype classifications based on conventional immunohistochemical and fluorescent in situ hybridization determinations were used: #1: Four groups segregated according to the combination of hormone receptor (HR) and HER2 status; #2: Intrinsic subtype classification (Triple Negative (TN), HER2, Luminal B and Luminal A). Both subtype classifications yielded prognostic and predictive information. HR +/HER2- patients (and Luminal A patients) had a significantly better outcome than the other subgroups of patients. The superiority of FEC-P over FEC was clearly more marked in HR-/HER2- patients (TN patients), particularly in the subset with basal phenotype (TN and either EGFR+ or cytokeratins 5/6+). The Luminal A subtype also achieved a significant benefit with FEC-P. The molecular-defined subgroup of TN was clearly predictive of better response to treatment with FEC-P. Luminal A patients had the best prognosis and also have a better outcome with weekly paclitaxel.


Concentrations of cadmium, cobalt, lead, nickel, and zinc in blood and fillets of northern hog sucker (Hypentelium nigricans) from streams contaminated by lead-zinc mining: implications for monitoring.
Lead (Pb) and other metals can accumulate in northern hog sucker (Hypentelium nigricans) and other suckers (Catostomidae), which are harvested in large numbers from Ozark streams by recreational fishers. Suckers are also important in the diets of piscivorous wildlife and fishes. Suckers from streams contaminated by historic Pb-zinc (Zn) mining in southeastern Missouri are presently identified in a consumption advisory because of Pb concentrations. We evaluated blood sampling as a potentially nonlethal alternative to fillet sampling for Pb and other metals in northern hog sucker. Scaled, skin-on, bone-in "fillet" and blood samples were obtained from northern hog suckers (n = 75) collected at nine sites representing a wide range of conditions relative to Pb-Zn mining in southeastern Missouri. All samples were analyzed for cadmium (Cd), cobalt (Co), Pb, nickel (Ni), and Zn. Fillets were also analyzed for calcium as an indicator of the amount of bone, skin, and mucus included in the samples. Pb, Cd, Co, and Ni concentrations were typically higher in blood than in fillets, but Zn concentrations were similar in both sample types. Concentrations of all metals except Zn were typically higher at sites located downstream from active and historic Pb-Zn mines and related facilities than at nonmining sites. Blood concentrations of Pb, Cd, and Co were highly correlated with corresponding fillet concentrations; log-log linear regressions between concentrations in the two sample types explained 94% of the variation for Pb, 73-83% of the variation for Co, and 61% of the variation for Cd. In contrast, relations for Ni and Zn explained <12% of the total variation. Fillet Pb and calcium concentrations were correlated (r = 0.83), but only in the 12 fish from the most contaminated site; concentrations were not significantly correlated across all sites. Conversely, fillet Cd and calcium were correlated across the range of sites (r = 0.78), and the inclusion of calcium in the fillet-to-blood relation explained an additional 12% of the total variation in fillet Cd. Collectively, the results indicate that blood sampling could provide reasonably accurate and precise estimates of fillet Pb, Co, and Cd concentrations that would be suitable for identifying contaminated sites and for monitoring, but some fillet sampling might be necessary at contaminated sites for establishing consumption advisories.


The 844ins68 polymorphism of the cystathionine beta-synthase gene is associated with schizophrenia.
A subtle genetic defect in homocysteine metabolism is thought to play an etiologic role in schizophrenia. Cystathionine-beta-synthase (CBS) is a key enzyme related to homocysteine levels. The aim of the present study was to search for association between the 844ins68 polymorphism of the CBS gene and schizophrenia in a large Russian sample using case-control and family-based designs. The sample comprised 1135 patients, 626 controls and 172 families. There was a trend for association between the 844ins68 polymorphism and schizophrenia in the case-control study, with higher frequency of the insertion in the control group. The FBAT revealed a statistically significant difference in transmission of alleles from parents to the affected proband, with preferential transmission of the variant without insertion. When the sample of patients was stratified by sex and forms of schizophrenia, the significantly lower frequency of insertion was observed in the group of female patients with chronic schizophrenia (n=180) as compared to psychiatrically well women. The insertion variant has been reported earlier to be related to decreased levels of homocysteine and thus thought to play a protective role. In conclusion, our study revealed a possible relation of the CBS 844ins68 polymorphism to schizophrenia.


Magnesium removal impairs the regulatory role of rat endothelium.
Vascular endothelium has been shown to play an important role in the regulation of vascular tone and, hence, impairment of the endothelium may induce hypertension. Although magnesium (Mg) deficiency could induce hypertension, the role of Mg on the endothelium is unclear. We examined the effects of Mg removal on endothelium-dependent and -independent responses using ring preparations of femoral arteries obtained from spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Norepinephrine (10(-9)-10(-4) M) evoked concentration-dependent contractions in arteries with endothelium. The maximal response was greater in SHR than in WKY. Removal of external Mg augmented the contraction in WKY but not in SHR. As a result, the contraction obtained in arteries with endothelium was identical in the two groups. Removal of the endothelium enhanced the contraction in both strains, with a greater response occurring in WKY than in SHR in Krebs, but not in Mg-free, solution. As a result, in arteries without endothelium, the contractions were identical in WKY and SHR both in Krebs and Mg-free solutions. Acetylcholine (10(-9)-10(-4) M) evoked concentration-dependent relaxation in arteries with, but not in those without, endothelium obtained from WKY and SHR. The relaxation did not differ between the two strains, nor was it altered by Mg removal. Thus, Mg removal impairs inhibitory function of the endothelium against contraction induced by norepinephrine, without affecting endothelium-dependent relaxation in response to acetylcholine, in the rat femoral artery. The effect of Mg removal is not apparent in SHR. The fact that after removal of external Mg the contraction in response to norepinephrine in arteries with endothelium is identical in WKY and SHR suggests that a normotensive artery with Mg deficiency may mimic a hypertensive artery through endothelial impairment.


The multi-channel cochlear implant and the relief of severe-to-profound deafness.
This personal reflection outlines the discoveries at the University of Melbourne leading to the multi-channel cochlear implant, and its development industrially by Cochlear Limited. My earlier experimental electrophysiological research demonstrated temporal coding occurred for only low frequencies, i.e. below 200-500 pulses/second. I was able to confirm these findings perceptually in behaviourally conditioned animals. In addition, these studies showed that temporal discrimination occurred across spatial coding channels. These experimental results correlated with the later conscious experience for electrical stimulation in my implant patients. In addition, the mid-to-high frequencies were coded in part by place of stimulation using bipolar and monopolar stimulation to restrict current spread. Furthermore, place of stimulation had the qualities of sharpness and dullness, and was also experienced as vowels. Owing to the limitation in coding speech with a physiological model due to the overlap of electrical current leading to unpredictable variations in loudness, a speech coding strategy that extracted the most important speech features for transmission through an electro-neural 'bottle-neck' to the brain was explored. Our inaugural strategy, discovered in 1978, extracted the second formant for place of stimulation, voicing for rate of stimulation, and sound pressure for current level. This was the first coding strategy to provide open-set speech understanding, as shown by standard audiological tests, and it became the first clinically successful interface between the world and human consciousness. This strategy was improved with place coding for the third formant or high-frequency spectrum, and then the spectral maxima. In 1989, I operated on our first patient to receive a bilateral implant, and in 1990, the first with a bimodal processor. The psychophysics and speech perception for these showed that the stimuli from each side could be fused into a single image, and localized according to differences in intensity and time of arrival of the stimuli. There were significant improvements for speech perception in noise. In 1985, I implanted our first children with the multi-channel prosthesis and found that speech understanding and spoken language were greatly improved the younger the child at surgery, and especially when younger than 12 months. Speech understanding was strongly related to the development of place coding. In 1990, the US Food and Drug Administration approved the implant for deaf children, the first by any world health regulatory body making it the first major advance in helping deaf children to communicate.


[Homeopathy in veterinary medicine and its pharmacologic/toxicologic and drug regulatory evaluation].
This review gives a summary of the definitions, delimitations and principles of homeopathy and its potential mechanisms of action, which is followed by an overview and critical evaluation of the most important homeopathic drugs registered for treatment of animals. It is shown that several of the marketed homeopathic drugs for treatment of animals violate current drug laws and represent a risk for both the animals and the consumer of food produced from animals. Based on these potential risks of homeopathic treatments, new EC regulations were recently published, which will markedly affect (and hopefully improve) the current situation of veterinary homeopathic drugs.


Specific binding of lac repressor to linear versus circular polyoperator molecules.
Gel shift assays were used to examine the binding of the lactose (lac) repressor to polyoperator DNA molecules. Specific binding was differentiated from nonspecific DNA association by (i) equilibrating repressor-operator complexes below the nonspecific association constant and (ii) demonstrating the effects of the inducer isopropyl beta-D-thiogalactoside (IPTG) on the formation of repressor-operator complexes. With the linear polyoperator molecules, all eight operator sites could be simultaneously bound by distinct repressors. However, with circular molecules, the eight operator sites were saturable by repressor only in the nicked circular state and not in the covalently closed circular form. Under the experimental conditions used, there was no evidence of bifunctional repressor binding or loop formation. The results suggest that the conformational perturbation of DNA that occurs upon specific repressor binding was retained in topologically closed molecules and could modify other operator sites so as to make them unavailable for specific binding.


Thallium antagonism toward potassium dependent systems.
When a number of Group 1A chlorides were added to yeast solutions which were inhibited by 20 mM Tl+, the greatest restorative effect was shown by KCl, with a lesser effect by NH4Cl. Sodium, rubidium and cesium chlorides had no significant effect on Tl+-inhibited CO2 production, and lithium chloride inhibited the system even further. Removal of potassium ions by dialysis reduced CO2 production by about 70% and the restorative effect of potassium was markedly reduced when this ion was added in the presence of thallium.


Biochemical aspects of chemical carcinogenesis.
This article briefly outlines three major biochemical problems in relation to the presence of chemical carcinogens in mammalian cells: (a) the enzymatic systems responsible for the chemical carcinogen metabolism; (b) the nature of the reactive metabolites and (c) the cellular target(s). References and examples are only given for the field of the polycyclic aromatic hydrocarbons.


[Molecular diagnosis of CHARGE syndrom].
CHARGE (coloboma, heart defects, atresia choanae, retarded growth and development, genital anomalies, ear anomalies) is a genetically heterogeneous syndrome in which CHD7 (chromodomain helicase DNA-binding protein 7) mutations account for about 60% of the cases. There is no obvious genotype-phenotype correlation but the majority of the patients fulfils the diagnostic criteria previously proposed. CHARGE syndrome should be considered in children with facial asymmetry, colobomas or choanal atresia; ear abnormalities are of great diagnostic value.


Radical radiotherapy for localized prostate cancer in elderly.
Prostate cancer is an age related neoplasm, with high incidence in the group of elderly man. The correct management must to be balanced between the benefits of the treatment and its disadvantages. Radiotherapy as definitive treatment is commonly reserved for older patients and patients with high surgical risk and is widely used as a treatment of choice. The aim of this study was to determine the role of radical radiotherapy for localized prostate carcinoma in patients 70 years age or older concerning treatment morbidity, local control, disease free and overall survival. A clinical prospective non-randomized study was performed including 103 elderly patients with an age 70 or above, between January 1991 and April 2005, at the Institute for Oncology and Radiology of Serbia. Median age of patients was 74,89 years (range 70- 80 years). Stage distribution was as follows: stage A--3 patients (2.9%), stage B--69 patients (67%) and stage C--31 patients (30.1%). Out of 103 patients, initial PSA value was noted in 87 patients. The mean value of initial PSA was 18,06 ng/ml. Radical radiotherapy was conducted on megavoltage linear accelerators with high energy photons (10, 18 MeV) and total tumor dose of 65 Gy. Low grade acute complications were registered in 70 patients (65%). Mean follow up time was 40, 13 months. The disease outcome at the last follow up show that 79 patients (76.7%) had no evidence of disease and 24 patients (23.3%) relapsed. Overall survival rates were 65, 29% and 44, 52% and disease free survival 66, 59% and 63, 26% at 5 and 10 years. Disease specific survival was at 5 and 10 years 73,32% and 65, 42% respectively. Late sequelas (gradus I and II) are registered in 22 patients (21.36%), out of 103. Radical radiotherapy for localized carcinoma of the prostate is effective treatment option in elderly patients with good local control, present treatment tolerance providing good quality of life and long-term cure.


The impact of trivial attributes on inaction inertia.
In this research, I investigate the role of trivial attributes in mitigating inaction inertia arising from having missed a much lower price than the discounted price at which a product is currently available. I show that a trivial attribute reduces regret by providing a silver lining against a psychological deficit caused by an unfavorable, intertemporal, price discrepancy, and restores purchase likelihood. I also show that a trivial attribute has an asymmetric effect on inaction inertia and while its addition mitigates the tendency, its subtraction does not exacerbate it. Further, increasing the number of trivial attributes added to a product does not have an additive effect on mitigating inaction inertia. Finally, I show that if alternative mechanisms can curb inaction inertia, then a trivial attribute does have an additional effect on purchase likelihood. The results suggest that synchronizing depth of price discounts with trivial changes in product attributes can help marketers better manage sales across price promotion cycles. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


[Clinical picture and diagnosis of refractory anemia with an excess of blasts and with bone marrow hypoplasia].
Clinical picture of refractory anemia with excessive blasts and bone marrow hypoplasia (RAEB with BMH) has been described in 22 patients. Statistically significant differences between RAEB with BMN and hypoplastic anemia have been presented. The problems of the differential diagnosis of RAEB with BMH have been discussed.


Cisterna magna clot and subsequent post-hemorrhagic hydrocephalus.
Posthemorrhagic hydrocephalus (PHH) is an ominous complication of intraventricular hemorrhage (IVH) in premature infants. Previous studies have correlated lateral intraventricular clot with subsequent PHH, but there are no studies assessing the outcome of clot in the cisterna magna (CM). The purpose of this study was to determine if the identification of clot in the CM on the initial positive cranial ultrasound for intraventricular hemorrhage increased the risk of subsequent PHH. A review of ultrasound records over a 4-year period identified 41 neonates with at least grade 2 IVH who had specific CM views prospectively performed. Thirty-six survived more than 3 months. Overall, 22 (61%) developed hydrocephalus. On the initial positive cranial ultrasound, CM blood was identified in 21 (58%). Of these 18 (86%) developed hydrocephalus [odds ratio (OR) 16.5, confidence interval (CI) 2.5-125.7, P < 0.001] and 14 (67%) required intervention or remained dilated (OR 28.0, CI 2.8-1265.8). All patients that required permanent shunt placement had initial CM clot (P < 0.01). Initial ventriculomegaly was not a significant predictor of subsequent hydrocephalus, but a dilated third ventricle (> or = 8 mm) was (OR 9.0, CI 1.2-103.3, P < 0.04). Asymmetric intraventricular clot filling of more than 50% was not predictive of hydrocephalus, but symmetric clot of more than 50% was (OR 10.8, CI 1.4-61.6, P < 0.01). Nine neonates had concomitant parenchymal damage with varying outcomes (three shunted, two persistent ventriculomegaly, four resolved with normal sized ventricles). In this study CM clot significantly increased the risk and was a better predictor of posthemorrhagic hydrocephalus than initial hydrocephalus.


Reduced MPTP neurotoxicity in striatum of the mutant mouse tottering.
The effects of MPTP treatment (4 x 10 mg/kg, 2-h intervals) on in vivo striatal binding of (+)-alpha-[3H]dihydrotetrabenazine ((+)-[3H]DTBZ) to the vesicular monoamine transporter type 2 (VMAT2) were examined in wild type (+,+) and tottering (tg/tg) mice of the C57BL/6J strain. The tottering mutant has been previously characterized as having hyperinnervation of noradrenergic terminals in the brain, with increased concentrations of norepinephrine and increased numbers of VMAT2 binding sites. In wild-type mice, MPTP caused a significant decrease in specific striatal (+)-[3H]DTBZ binding in both males (-71%) and females (-57%), consistent with dopaminergic terminal losses. In the tottering mice, the neurotoxic effects of MPTP were diminished, with smaller losses of (+)-[3H]DTBZ binding observed both in males (-45%) and females (-26%). These results are consistent with the hypothesis that vesicular storage (as a result of hyperinnervation) offers neuroprotection toward MPTP toxicity, although the confounding effects of increases in norepinephrine concentrations or changes in calcium ion channel function (both also characteristics of the tottering mutant) cannot be ruled out. The tottering mutant does, however, offer another animal model to examine the biochemical features responsible for MPTP toxicity.


Regulatory roles of transforming growth factor beta family members in folliculogenesis.
Bidirectional signaling between the oocyte and surrounding somatic cells is absolutely essential for successful germ cell development in mammals. Oocytes secrete proteins that are necessary for granulosa cells growth and differentiation, whilst granulosa cells regulate oocyte development and integrate ovarian function with the rest of the body by orchestrating gonadal steroidogenesis. The importance of communication between the oocyte and granulosa cells is highlighted by genetic deletion of members of the transforming growth factor beta (TGFβ) family and their downstream signaling components. Such knockout models have uncovered an interesting spectrum of reproductive phenotypes that have greatly advanced our knowledge of ovarian function and dysfunction. The current review focuses on some of the more recent transgenic mouse models that elucidate the intraovarian TGFβ signaling vital for oocyte and granulosa cell development.


Fine structure and formation of the eggshell in scorpionfly Panorpa liui Hua (Mecoptera: Panorpidae).
The morphology and formation of the eggshell in the scorpionfly Panorpa liui Hua were examined with light microscopy and scanning and transmission electron microscopy. During oogenesis of the scorpionfly, the follicle cells multiply by mitotic divisions and diversify into four morphologically distinct subpopulations, three of which are engaged in the eggshell formation and mold various parts of chorion. The eggshell consists of three layers: An inner vitelline membrane, an outer chorion, and a precursor extrachorion. The chorion constitutes a very compact endochorion, a rough fibrillar exochorion, and a polygonal meshwork of elevated ridges. At proximal end of ovarioles the chorion of matured oocyte is covered with a loose membrane, which might be the remnant of follicle cells. The jelly substance, which acts as lubricant to protect the oviducts and ovulated eggs during ovulation, might add to the top of polygonal ridges as the outermost extrachorion after oviposition. The eggshell formation process in Panorpa is tentatively proposed.


Neural network and support vector machine for the prediction of chronic kidney disease: A comparative study.
This paper aims to assist in the prevention of Chronic Kidney Disease (CKD) by utilizing machine learning techniques to diagnose CKD at an early stage. Kidney diseases are disorders that disrupt the normal function of the kidney. As the percentage of patients affected by CKD is significantly increasing, effective prediction procedures should be considered. In this paper, we focus on applying different machine learning classification algorithms to a dataset of 400 patients and 24 attributes related to diagnosis of chronic kidney disease. The classification techniques used in this study include Artificial Neural Network (ANN) and Support Vector Machine (SVM). To perform experiments, all missing values in the dataset were replaced by the mean of the corresponding attributes. Then, the optimized parameters for the Artificial Neural Network (ANN) and Support Vector Machine (SVM) techniques were determined by tuning the parameters and performing several experiments. The final models of the two proposed techniques were developed using the best-obtained parameters and features. The empirical results from the experiments indicated that ANN performed better than SVM, with accuracies of 99.75% and 97.75%, respectively, indicating that the outcome of this study is very promising.


Changes in participation patterns of youth with physical disabilities following the Pathways and Resources for Engagement and Participation intervention: A time-geography approach.
The PREP (Pathways and Resources for Engagement and Participation), an innovative 12-week occupational therapy intervention that focuses on changing the environment, was found effective in improving the participation of youth in specific chosen community-based activities. To complement existing evidence, this study explored changes in overall participation patterns of youth with physical disabilities following the PREP intervention. Guided by time-geography approach, 13 youth aged 12-17 completed a 24-hr diary using the Aday app during one typical weekday and another day during the weekend, pre- and post-intervention. Data of 50 diaries were plotted and analyzed using the VISUALTimePAcTS program. Following the PREP, youth were engaged in less digital media and more in study-related activities. Number of occurrences and time spent doing activities with friends were greater post-intervention, whereas time spent doing activities at home was quite similar, particularly during the weekdays. During the weekends, however, youth spent slightly less time at home. Findings provide preliminary support for the effectiveness of the PREP, extending beyond the accomplishment of specific targeted activities towards a change in the overall daily patterns of youth. Such knowledge can redirect occupational therapists' attention to environment-focused interventions involving real-life experiences.


Chronic prenatal ethanol exposure alters hippocampal GABA(A) receptors and impairs spatial learning in the guinea pig.
Chronic prenatal ethanol exposure (CPEE) can injure the developing brain, and may lead to the fetal alcohol syndrome (FAS). Previous studies have demonstrated that CPEE upregulates gamma-aminobutyric acid type A (GABA(A)) receptor expression in the cerebral cortex, and decreases functional synaptic plasticity in the hippocampus, in the adult guinea pig. This study tested the hypothesis that CPEE increases GABA(A) receptor expression in the hippocampus of guinea pig offspring that exhibit cognitive deficits in a hippocampal-dependent spatial learning task. Timed, pregnant guinea pigs were treated with ethanol (4 g/kg maternal body weight per day), isocaloric-sucrose/pair-feeding, or water throughout gestation. GABA(A) receptor subunit protein expression in the hippocampus was measured at two development ages: near-term fetus and young adult. In young adult guinea pig offspring, CPEE increased spontaneous locomotor activity in the open-field and impaired task acquisition in the Morris water maze. CPEE did not change GABA(A) receptor subunit protein expression in the near-term fetal hippocampus, but increased expression of the beta2/3-subunit of the GABA(A) receptor in the hippocampus of young adult offspring. CPEE did not change either [(3)H]flunitrazepam binding or GABA potentiation of [(3)H]flunitrazepam binding, but decreased the efficacy of allopregnanolone potentiation of [(3)H]flunitrazepam binding, to hippocampal GABA(A) receptors in adult offspring. Correlational analysis revealed a relationship between increased spontaneous locomotor activity and growth restriction in the hippocampus induced by CPEE. Similarly, an inverse relationship was found between performance in the water maze and the efficacy of allopregnanolone potentiation of [(3)H]flunitrazepam binding in the hippocampus. These data suggest that alterations in hippocampal GABA(A) receptor expression and pharmacological properties contribute to hippocampal-related behavioral and cognitive deficits associated with CPEE.


Smoking cessation among Chinese young smokers: does gender and age difference matters and what are the predictors?
This study assessed the gender and age differences in smoking cessation among the Chinese youth and identified factors associated with quitting smoking. This was a clinic based cross-sectional study with longitudinal components among 129 Chinese young smokers. All services in the clinic including one week's supply of nicotine replacement therapy (NRT) were free. We used structured questionnaires at baseline and at 1, 3 and 12 months. The analysis was by intention-to-treat basis. At 12 month follow up, the 7 day point prevalence quit rate (abstinence from tobacco smoking during the 7 days preceding the follow up) was 19% (25/129) and 36% (25/69) among all the attendees and among those who were successfully followed up, respectively. There was no significant gender or age differences in the quitting outcome but females and the older youth reported more withdrawal symptoms. Not reporting any withdrawal symptoms at 3 months follow up and adherence to use NRT for at least 4 weeks were significant predictors of quitting. A clinic-based smoking cessation service among Chinese young smokers produced an acceptable quit rate with no gender and age difference, indicating that a more general quit smoking approach could be taken for the youth.