The sex differences of the behavior response to early Life immune stimulation: Microglia and astrocytes involvement.

It is well known that inflammatory challenge during the prenatal period results in permanent changes in glial cells and behavior in adulthood. However, it is unknown whether inflammatory challenge during the infantile period may have permanent sexually-dimorphic effects on microglia and astrocytes in vivo, which in turn may be associated with sex differences in adult behavior. In this study, we have evaluated whether postnatal injection of lipopolysaccharide (LPS; 250µg/kg, i.p. on postnatal day 14) induces depressive and less anxiety-like behaviors, glial cell activation, pro-inflammatory cytokine (TNF-alpha) secretion and sexually dimorphic responses in adulthood. Postnatal day 14 (P14) male and female Wistar rats received an intraperitoneal (ip) injection of LPS or PBS. Three months later, animals were tested in the Open Field (OF), the Elevated Plus Maze (EPM) and the Forced Swimming Test (FST) to assess the level of anxiety and depression-like behavior. Hippocampal proinflammatory cytokine TNF-alpha concentration and the number of astrocytes and microglia were estimated in the dentate gyrus, CA1, and CA3 in two regions of the hippocampus (ventral and dorsal). Our results showed that the administration of LPS resulted in less anxiety and depression-like behavior in males but not in females. However, the LPS-administration increased the number of microglia in the dorsal and ventral hippocampus areas in females more than male, while no significant differences in TNFα level had been detected between the LPS-rats treated and their controls. Interestingly, LPS resulted in an increase in the number of astrocytes in both areas of the hippocampus in a female. While in a male, our results showed a decrease in astrocytes number in the dorsal hippocampus, but no significant differences observed in ventral hippocampus. These findings indicate that an immune challenge in infantile rats induces a ventral and dorsal hippocampus damage in female more than in male, without affecting significantly the affective behavior changes in the female. The results also showed that small changes in the male hippocampus can affect the behavior and induce a depression-like behavior.

Study of permeation and blocker binding in TMEM16A calcium-activated chloride channels.

We studied the effects of mutations of positively charged amino acid residues in the pore of X. tropicalis TMEM16A calcium-activated chloride channels: K613E, K628E, K630E; R646E and R761E. The activation and deactivation kinetics were not affected, and only K613E showed a lower current density. K628E and R761E affect anion selectivity without affecting Na(+) permeation, whereas K613E, R646E and the double mutant K613E + R646E affect anion selectivity and permeability to Na(+). Furthermore, altered blockade by the chloride channel blockers anthracene-9-carboxylic acid (A-9-C), 4, 4'-Diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) and T16inh-A01 was observed. These results suggest the existence of 2 binding sites for anions within the pore at electrical distances of 0.3 and 0.5. These sites are also relevant for anion permeation and blockade.

Effects of vibration therapy on hormone response and stress in severely disabled patients: a double-blind randomized placebo-controlled clinical trial.

PURPOSE: To assess the effects of vibration therapy (VT) on quality of life and hormone response in severely disabled patients compared with placebo. DESIGN: A longitudinal prospective, double-blind, randomized placebo-controlled trial, with pre and postintervention assessments. METHODS: A total of 20 severely disabled individuals were recruited from a National Reference Centre in Spain: 13 (65%) men and 7 (35%) women, 45.5 ± 9.32 years of age (range 41: 22-63). We evaluated their physical stress and state anxiety. RESULTS: No statistically significant changes were found in the socio-psychological variables studied, while in the experimental group state anxiety decreased significantly with p < 0.01 (Z = 2.38; one-tailed p = .009) and, among the biological variables, the level of cortisol fell (p = 0.03). CONCLUSION: Short periods of exposure to low-frequency and low-amplitude local vibration are a safe and effective mechanical stimulus that can have a positive effect in terms of hormone response. CLINICAL RELEVANCE: VT can be considered to have an anti-stress effect.

Crystal structure of ethyl 3-anilino-2-{[bis-(methyl-sulfan-yl)methyl-idene]amino}-3-oxopropano-ate.

The mol-ecular conformation of the title compound, C14H18N2O3S2, is stabilized by intra-molecular N-H⋯N and C-H⋯O hydrogen bonds. The crystal packing is characterized by a series of C-H⋯O hydrogen bonds, resulting in a three-dimensional network.

[Does Alzheimer's disease exist in all primates? Alzheimer pathology in non-human primates and its pathophysiological implications (II)]. / ¿Existe la enfermedad de Alzheimer en todos los primates? Patología Alzheimer en primates no humanos y sus implicaciones fisiopatológicas (II).

INTRODUCTION: In the ageing process there are some species of non-human primates which can show some of the defining characteristics of the Alzheimer's disease (AD) of man, both in neuropathological changes and cognitive-behavioural symptoms. The study of these species is of prime importance to understand AD and develop therapies to combat this neurodegenerative disease. DEVELOPMENT: In this second part of the study, these AD features are discussed in the most important non-experimental AD models (Mouse Lemur -Microcebus murinus, Caribbean vervet -Chlorocebus aethiops, and the Rhesus and stump-tailed macaque -Macaca mulatta and M. arctoides) and experimental models (lesional, neurotoxic, pharmacological, immunological, etc.) non-human primates. In all these models cerebral amyloid neuropathology can occur in senility, although with different levels of incidence (100% in vervets;<30% in macaques). The differences between normal and pathological (Alzheimer's) senility in these species are difficult to establish due to the lack of cognitive-behavioural studies in the many groups analysed, as well as the controversy in the results of these studies when they were carried out. However, in some macaques, a correlation between a high degree of functional brain impairment and a large number of neuropathological changes ("possible AD") has been found. CONCLUSIONS: In some non-human primates, such as the macaque, the existence of a possible continuum between "normal" ageing process, "normal" ageing with no deep neuropathological and cognitive-behavioural changes, and "pathological ageing" (or "Alzheimer type ageing"), may be considered. In other cases, such as the Caribbean vervet, neuropathological changes are constant and quite marked, but its impact on cognition and behaviour does not seem to be very important. This does assume the possible existence in the human senile physiological regression of a stable phase without dementia even if neuropathological changes appeared.

Anion permeation in calcium-activated chloride channels formed by TMEM16A from Xenopus tropicalis.

Calcium-activated chloride channels (CaCC) formed by anoctamin1/TMEM16A subunits are ubiquitously expressed, and these channels are known to prevent polyspermy in amphibian oocytes. Here, we describe a TMEM16A clone isolated from Xenopus tropicalis oocytes (xtTMEM16A) and how the anion permeation properties are modified in single-site mutants of the ion pore. The anion permeability sequence was SCN(-) > I(-) > Br(-) > Cl(-) > gluconate (relative permeabilities 5.6:3.0:2.1:1:0.2, respectively). Dose-response curves indicated that the voltage-dependent half-maximal concentration for Ca(2+) activation (K d of the Hill equation at +100 mV) was 120 nM in normal external Cl(-), whereas it was displaced leftward to 75 nM Ca(2+), when I(-) replaced Cl(-). The I(-):Cl(-) mole fraction (MF) of the external solution was varied in order to gain insight into the permeation mechanism of the pore. No anomaly in MF behavior was observed for conductance, but it was observed for current reversal potential, which deviated from the prediction of the Goldman-Hodgkin-Katz equation. Mutations of positively charged amino acids in the pore, R646 and R761, to glutamate resulted in reduction of the relative permeability to I(-). Data from the wild type and mutants could be well fitted by a three-barrier, two-site permeation model. This suggests a multi-ion pore with at least two binding sites for anions, with R646 mole fraction closer to the extracellular membrane surface--being important for the stability of both sites--and R761--located deeper within the membrane--mainly affecting the innermost binding site. Considerations of xtTMEM16A putative pore region topology are discussed in the light of two alternative topological models of the protein.

Efficacy of florfenicol injection in the treatment of Mycoplasma hyopneumoniae induced respiratory disease in pigs.

This study investigated the efficacy of a single intramuscular injection of a new formulation of florfenicol to treat clinical respiratory disease following experimental Mycoplasma hyopneumoniae infection. M. hyopneumoniae-free piglets were allocated to three groups, namely, a treatment group (TG) and a positive control group (PCG), which were both inoculated endotracheally with a highly virulent isolate of M. hyopneumoniae, and a negative control group. At the onset of clinical disease, the TG received a single injection of florfenicol (30 mg/kg). All pigs were euthanased 4 weeks post-infection. Clinical symptoms were significantly reduced in the TG in comparison with the PCG. Average daily gain, feed conversion ratio, mortality and lung lesions were improved in the TG compared to the PCG, but the differences were not statistically significant.

[Does Alzheimer's disease exist in all primates? Alzheimer pathology in non-human primates and its pathophysiological implications (I)]. / ¿Existe la enfermedad de Alzheimer en todos los primates? Afección de Alzheimer en primates no humanos y sus implicaciones fisiopatológicas (I).

INTRODUCTION: Many publications consider that Alzheimer's disease (AD) is exclusive to the human species, and that no other animal species suffers from the disease. However, various studies have shown that some species can present with some of the defining characteristics of the human disease, including both neuropathological changes and cognitive-behavioural symptoms. DEVELOPMENT: In this work, the results published (PubMed) on senile brain changes in non-human primates of different degrees of evolution, are reviewed. The neuropathological changes associated with the accumulation of amyloid or highly phosphorylated tau protein are rare outside the primate order, but in all the sub-orders, families, genera and species of non-human primates that have been studied, some senile individuals have shown amyloid accumulation in the brain. In fact, in some species the presence of these deposits in senility is constant. Changes related to the accumulation of tau protein are always of very little significance, and have been detected only in some non-human primate species, both little evolved and highly evolved. In different species of non-human primates, some types of cognitive-behavioural changes are more common in some senile individuals when compared with both normal adult individuals and other senile individuals of the species. The importance of determining the longevity of the species in different habitats (natural habitats, new habitats, semi-captivity, captivity) is stressed in these studies. CONCLUSIONS: Morphological, histochemical and cognitive-behavioural features similar to those observed in elderly humans are present in senile non-human primates. Moreover, other characteristics seen in non-human primates could be indicative of a pathological «Alzheimer type¼ ageing.

Effect of dilution temperature on boar semen quality.

As boar semen is very sensitive to cold shock and changes in temperature during semen processing can have a profound impact on semen quality, the effect of the extender temperature at the time of dilution was investigated in a two-step dilution protocol for boar semen being processed for liquid storage. Fifteen boars of different breeds and ages from a commercial artificial insemination centre were included. One ejaculate per boar was collected and processed with Beltsville Thawing Solution semen extender. Each ejaculate was diluted (1 : 1) at 30 °C, and subsequently, the samples were diluted (30 × 10(6) sperm/ml) with either preheated extender [29.3 °C ± 0.2 °C, group A (GA)] or extender at room temperature [22.7 °C ± 0.6 °C, group B (GB)]. Samples were transported to the Faculty of Veterinary Medicine (University of Ghent, Belgium) in two isotherm boxes (one per group), stored at 17 °C and investigated for three consecutive days (D0 to D2). At D0, D1 and D2, motility parameters [computer-assisted semen analysis (CASA)] and the per cent of sperm with intact membrane (% IM) by eosin nigrosin staining were evaluated. At D0 and D2, the % of sperm with intact acrosome (% IA) was studied by Pisum sativum agglutinin staining. The average temperature of the 1 : 1 dilution was 29.4 °C ± 1.1 °C immediately after extender addition. No significant differences were found between groups for per cent motility [79.3 ± 9.0 for GA and 81.1 ± 9.2 for GB (p = 0.372)], % progressive motility [56.5 ± 13.3 for GA and 58.4 ± 13.8 for GB (p = 0.737)] or any CASA parameter. No differences were found for % IM [85.1 ± 10.7 and 84.5 ± 3.8 for GA and GB, respectively (p = 0.761)] and % IA [72.2 ± 9.4 for GA and 68.3 ± 16.6 for GB (p = 0.792)]. In conclusion, when a two-step dilution is performed, preheating the extender for the second dilution to match the semen temperature did not result in better semen quality compared to a dilution at a moderate room temperature.

Maternal deprivation and adolescent cannabinoid exposure impact hippocampal astrocytes, CB1 receptors and brain-derived neurotrophic factor in a sexually dimorphic fashion.

We have recently reported that early maternal deprivation (MD) for 24 h [postnatal day (PND) 9-10] and/or an adolescent chronic treatment with the cannabinoid agonist CP-55,940 (CP) [0.4 mg/kg, PND 28-42] in Wistar rats induced, in adulthood, diverse sex-dependent long-term behavioral and physiological modifications. Here we show the results obtained from investigating the immunohistochemical analysis of CB1 cannabinoid receptors, glial fibrillary acidic protein (GFAP) positive (+) cells and brain-derived neurotrophic factor (BDNF) expression in the hippocampus of the same animals. MD induced, in males, a significant increase in the number of GFAP+ cells in CA1 and CA3 areas and in the polymorphic layer of the dentate gyrus (DG), an effect that was attenuated by CP in the two latter regions. Adolescent cannabinoid exposure induced, in control non-deprived males, a significant increase in the number of GFAP+ cells in the polymorphic layer of the DG. MD induced a decrease in CB1 expression in both sexes, and this effect was reversed in males by the cannabinoid treatment. In turn, the drug "per se" induced, in males, a general decrease in CB1 immunoreactivity, and the opposite effect was observed in females. Cannabinoid exposure tended to reduce BDNF expression in CA1 and CA3 of females, whereas MD counteracted this trend and induced an increase of BDNF in females. As a whole, the present results show sex-dependent long-term effects of both MD and juvenile cannabinoid exposure as well as functional interactions between the two treatments.

Comparison of oral versus parenteral iron supplementation on the health and productivity of piglets.

The aim of this study was to compare oral iron supplementation in feed with a standard iron injection and assess the impact on the health and productivity of pigs. The reliability of a quick test (HemoCue) for the measurement of blood haemoglobin concentration was also investigated. Three pig herds, with a total of 88 sows and their piglets, were included in the study. Piglets in treatment group O were fed a special iron-rich feed on days 2 to 4, 5 to 7 and 8 to 12 of lactation using a specially designed feeding device. Piglets in group IM received 200 mg of an iron dextran complex intramuscularly at three days of age. Haemoglobin concentrations and performance of the piglets were compared between groups. The mean haemoglobin concentrations in pigs at weaning were 131.4 and 116.4 g/l for pigs in groups O and IM, respectively (P<0.01). Daily weight gain (253.9 v 248.8 g/day) and piglet mortality (11.4 v 12.2 per cent) were slightly better in group O than in group IM (P>0.05).

[Analysis of patients violence in primary care]. / Análisis de la violencia del paciente en atención primaria.

OBJECTIVE: Main aim: to determine the frequency of violence in primary care. Secondary aims: to analyse its causes, consequences and connection with professional burnout and reduced motivation. DESIGN: Transversal, descriptive study. SETTING: Primary care. PARTICIPANTS: 68 primary care doctors from 4 districts in the province of Jaén (350, 19%). MAIN MEASUREMENTS: Self-administered questionnaire with an ad hoc design, sent out by mail and including personal and job details and doctors' views on the causes and consequences of burnout and violence, and the attitudes of the Andalusian Health Service (SAS) and professional bodies (overall reliability, Cronbach's alpha =.7898). RESULTS: 58% had suffered aggression (85% verbal abuse, 67.5% threats, 12.5% physical aggression). Being attacked was linked with attributing the responsibility to the patients (odds ratio [OR]=7.6, 95% confidence interval [CI], 2.5-23), with doing extra shifts (OR=6.3; 95% CI, 1.2-33), rigidity (OR=3.5; 95% CI, 1.2-10.7), inadequate handling of emotive situations (OR=3.2; 95% CI, 1.1-9.2,) and incompetence (OR=5.2; 95% CI, 1.6-17). Violence scored the lowest as cause of burnout and was linked to the job being less rewarding (OR=2.9; 95% CI, 1.0-7.8). It was linked to irritation with the SAS (OR=2.8; 95% CI, 1.0-7.5) and fear of reduced motivation (OR=2.8; 95% CI, 1.0-7.5), with this latter being linked to loss of social prestige (P<.01), feeling low self-esteem (P<.01), and depression (P<.01). CONCLUSIONS: Violence is more common than in the figures given by the International Labour Organisation. It is associated with distrust, lack of communication in health care delivery and incompetence. It is the cause of burnout that is least appreciated and it is linked to the job being less rewarding and to greater fear of reduced motivation.

Primary mesenteric liposarcoma of jejunum: presentation like a cystic mass.

This report describes a rare case of intra-abdominal liposarcoma in a 67-year-old woman. The patient presented at Internal Medicine Unit in May 2004, to study of thyroid pathology. The clinical examination was normal, except for the finding of an asymptomatic mass in the abdomen. The patient knew the existence of tumor since time ago, but she confesses to have only occasional discomfort. In the abdominal ultrasonography a solid mass with large cystic component was detected but relation with other organs was not clear. Computed tomography revealed the presence of a mass with solid and cystic components, in contact with small intestine in the left side of abdomen. A complete resection of tumor arising from mesentery of jejunum was performed successfully with end to end anastomosis. The gross specimen was lobulated and measured 8.5 x 7.5 cm. The histopathology analysis showed proliferating lipoblasts with irregular nuclei on a myxoid background, with plexiform vascular pattern, characteristics belongs to myxoid type liposarcoma. The patient is alive and well one year after removal of tumor. The uncommon site and the exceptional cystic morphology of tumor are discussed, and so it must be included the primary mesenteric liposarcoma in the differential diagnosis of intra-abdominal tumors with cystic large areas.

[Do the incontinent patients improve their equality of life using a humidity detector device?]. / Mejora un detector de humedad la calidad de vida de los pacientes con incontinencia urinaria?: un estudio piloto.

BACKGROUND: To evaluate the effect of a humidity detector device on the quality of life of patients with urinary incontinence IU. METHOD: Quasi-experimental study: a series of ten cases followed for a month. The devices were placed and the questionnaires filled in before and after using it for at least ten hours a day during a month. Health related quality of life was assessed through the questionnaires for IU convalidated and adapted to our specific environment: Urogenital Inventory Distress (UDI) and Incontinence Impact Questionary (IIQ). An improvement of 58 points by a four option Likert scale was considered a positive impact in the quality of life (IIQ). The scores obtained in UDI and IIQ are described before and after use the device and paried T test and Wilcoxon sign test were carried out to compare the scores obtained in each instance. The capacity to detect a difference of 58 points on the UDI scale was calculated (minimum relevant difference). A binomial test was undertaken to ascertain a probability of achieving an increase in the above mentioned index which would exceed the clinical relevance threshold. RESULTS: Average increase in IIQ improvement: x = 5.48 (Std Error = 20.43) 95% CI = -34.56 to 45.56. Average increase in UDI improvement: x = -11.87 (Std Error = 20.70) 95% IC = -52.45 to 28.70. The power of the analysis to detect as relevant a difference of a 588 point increase in IIQ 71.1% and probability of obtaining a relevant improvement in the questionnaire IIQ 10% (IC 95%) 0% to 39.4%. CONCLUSIONS: A negative impact in the Quality of Life due to frequent changes of incontinence pads.

Efficacy and safety of recombinant human activated protein C for severe sepsis.

BACKGROUND: Drotrecogin alfa (activated), or recombinant human activated protein C, has antithrombotic, antiinflammatory, and profibrinolytic properties. In a previous study, drotrecogin alfa activated produced dose-dependent reductions in the levels of markers of coagulation and inflammation in patients with severe sepsis. In this phase 3 trial, we assessed whether treatment with drotrecogin alfa activated reduced the rate of death from any cause among patients with severe sepsis. METHODS: We conducted a randomized, double-blind, placebo-controlled, multicenter trial. Patients with systemic inflammation and organ failure due to acute infection were enrolled and assigned to receive an intravenous infusion of either placebo or drotrecogin alfa activated (24 microg per kilogram of body weight per hour) for a total duration of 96 hours. The prospectively defined primary end point was death from any cause and was assessed 28 days after the start of the infusion. Patients were monitored for adverse events; changes in vital signs, laboratory variables, and the results of microbiologic cultures; and the development of neutralizing antibodies against activated protein C. RESULTS: A total of 1690 randomized patients were treated (840 in the placebo group and 850 in the drotrecogin alfa activated group). The mortality rate was 30.8 percent in the placebo group and 24.7 percent in the drotrecogin alfa activated group. On the basis of the prospectively defined primary analysis, treatment with drotrecogin alfa activated was associated with a reduction in the relative risk of death of 19.4 percent (95 percent confidence interval, 6.6 to 30.5) and an absolute reduction in the risk of death of 6.1 percent (P=0.005). The incidence of serious bleeding was higher in the drotrecogin alfa activated group than in the placebo group (3.5 percent vs. 2.0 percent, P=0.06). CONCLUSIONS: Treatment with drotrecogin alfa activated significantly reduces mortality in patients with severe sepsis and may be associated with an increased risk of bleeding.

[Metabolic control of diabetes mellitus en relation to the quality of the medical records]. / Control metabólico de la diabetes mellitus en relación con la calidad de las historias clínicas.

OBJECTIVE: To investigate whether there is a relationship between the quality of the clinical history (CH) in primary care and metabolic control of patients with diabetes (DM). DESIGN: Retrospective and observational. SETTING: 15 health centres in the Segovia Area. PATIENTS: 315 diabetic patients, selected at random from among those with a record of the type of DM, date and outcome of at least one HbA1c and treatment at the time of the most recent HbA1c. RESULTS: The quality of the clinical histories was measured through the mean of recording of the following items in the 13 months previous to the most recent HbA1c: weight and height, peripheral pulses, sensitivity, foot examination, creatinine, proteinuria, microalbuminuria, glucaemia levels, back of eye, ECG, and diet, tobacco and alcohol counselling. Other variables that could condition the HbA1c, chronic pathologies and those related to DM, were gathered too. Of patients treated with diet or oral diabetic drugs, patients with a clinical history of < or = 49% quality had a mean HbA1c of 7.40%, whereas those with CH of > or = 50% quality had an average of 6.94% (0.46 difference; 95% CI, 0.03-0.90; p = 0.038). This drop was not attributable to age, gender, years of evolution or BMI differences. The risk of having an HbA1c > or = 7.5% is double in patients with a CH of < or = 49% quality than in those with CH of > or = 50% quality (OR = 2.06; 95% CI, 1.14-3.72). In insulin-treated patients, no association between CH quality and HbA1c was found. CONCLUSIONS: Follow-up of the recommendations for clinical action is associated with better metabolic control in diabetics treated with diet--oral diabetic drugs. This association was not found in insulin-treated patients.