Physiology

In this study, we aimed to evaluate the protein expression profile of a spectrum of renal cell carcinomas (RCC) to find potential biomarkers for disease onset and progression and therefore, prospective therapeutic targets. A 2D-gel based proteomic analysis was used to outline differences in protein levels among different subtypes of renal cell carcinomas, including clear cell carcinomas, papillary lesions, chromophobe tumors and renal oncocytomas. Spot pattern was compared to the corresponding normal kidney from the same patients and distinctive, differentially expressed proteins were characterized by mass spectrometry. Twenty-one protein spots were found differentially expressed between clear cell RCC and normal tissue and 38 spots were found expressed in chromophobe tumors. Eleven proteins were identified, with most differentially expressed -by fold change-between clear cell tumors and the corresponding normal tissue. Two of the identified proteins, Triosephosphate isomerase 1 (TPI-1) and Heat Shock protein 27 (Hsp27), were further validated in a separate set of tumors by immunohistochemistry and expression levels were correlated with clinicopathologic features of the patients. Hsp27 was highly expressed in 82% of the tumors used for validation, and all cases showed strong immunoreactivity for TPI-1. In both Hsp27 and TPI-1, protein expression positively correlated with histologic features of the disease. Our results suggest that the subjacent cytogenetic abnormalities seen in different histological types of RCC are followed by specific changes in protein expression. From these changes, Hsp27 and TPI-1 emerged as potential candidates for the differentiation and prognosis in RCC.

In this study, aldose reductase (AR) was purified from sheep kidney using chromatographic methods and examined the interactions between some sulfonamides and the enzyme. According to results, sulfonamides display effective inhibitor features for sheep kidney AR with IC 50 values in the range of 37.27-87.65 lM and K i s in the range of 25.72 ± 6.45 to 73.56 ± 17.49 lM. The sulfonamides displayed different inhibition mechanisms. It was found that studied all compounds displayed non-competitive inhibition type except for 5-chlorothiophene-2-sulfonamide (1). It showed competitive inhibition. Among these compounds, 2,5-dichlorothiophene-3-sulfonamide compound (2) was showed the most potent AR inhibitor (K i : 25.72 ± 6.45). These compounds may be useful in the treatment of diabetic complications.

Sorbitol dehydrogenase activity and the hepatic and serum concentrations of sorbitol, glucose and fructose were quantified in diabetic mice. 2. Blood glucose concentrations were increased over 300% by diabetes and were decreased toward normal after insuiin-treatment. 3. Hepatic sorbitol concentrations ranged from 7-15 #mol/g and were highest in uncontrolled diabetic mice. 4. Hepatic concentrations of fructose and sorbitol were not affected by insulin administration. 5. Challenge with carbon tetrachloride (25 #I/kg i.p.) did not alter concentrations of glucose, sorbitol or fructose in blood or liver. 6. Sorbitol dehydrogenase activity in blood was increased similarly in normal, diabetic and insulintreated diabetic mice after CCI 4 administration. 7. The data indicate that sorbitol did not accumulate in diabetic mice, and that induction of diabetes did not increase the susceptibility of mice to CCI 4 hepatotoxicity as occurs in rats.

Male Largemouth Bass were sampled from two locations in Lake Mead (USA), a site influenced by treated municipal wastewater effluent and urban runoff (Las Vegas Bay), and a reference site (Overton Arm). Samples were collected in summer (July '07) and spring (March '08) to assess general health, endocrine and reproductive biomarkers, and compare contaminant body burdens by analyzing 252 organic chemicals. Sperm count and motility were measured in spring. Contaminants were detected at much higher frequencies and concentrations in fish from Las Vegas Bay than Overton Arm. Those with the highest concentrations included PCBs, DDTs, PBDEs, galaxolide, and methyl triclosan. Fish from Las Vegas Bay also had higher Fulton condition factor, hepatosomatic index, and hematocrit, and lower plasma 11-ketotestosterone concentration (KT). Gonadosomatic index (GSI) and sperm motility did not differ between sites, but sperm count was lower by nearly 50% in fish from Las Vegas Bay. A positive a...

Adult male Common Carp were sampled in 2007/08 over a full reproductive cycle at Lake Mead National Recreation Area. Sites sampled included a stream dominated by treated wastewater effluent, a lake basin receiving the streamflow, an upstream lake basin (reference), and a site below Hoover Dam. Individual body burdens for 252 contaminants were measured, and biological variables assessed included physiological [plasma vitellogenin (VTG), estradiol-17β (E2), 11-ketotestosterone (11KT)] and organ [gonadosomatic index (GSI)] endpoints. Patterns in contaminant composition and biological condition were determined by Principal Component Analysis, and their associations modeled by Principal Component Regression. Three spatially distinct but temporally stable gradients of contaminant distribution were recognized: a contaminant mixture typical of wastewaters (PBDEs, methyl triclosan, galaxolide), PCBs, and DDTs. Two spatiotemporally variable patterns of biological condition were recognized: a ...

In several types of central mammalian synapses, sustained presynaptic stimulation leads to a sequence of two components of synaptic vesicle release, reflecting the consecutive contributions of a fast-releasing pool (FRP) and of a slow-releasing pool (SRP). Previous work has shown that following common depletion by a strong stimulation, FRP and SRP recover with different kinetics. However, it has remained unclear whether any manipulation could lead to a selective enhancement of either FRP or SRP. To address this question, we have performed local presynaptic calcium uncaging in single presynaptic varicosities of cerebellar interneurons. These varicosities typically form “simple synapses” onto postsynaptic interneurons, involving several (one to six) docking/release sites within a single active zone. We find that strong uncaging laser pulses elicit two phases of release with time constants of ∼1 ms (FRP release) and ∼20 ms (SRP release). When uncaging was preceded by action potential–e...

GABA receptors have been described in the axonal compartment of neurons; contrary to dendritic GABA receptors, axonal GABA receptors usually induce depolarizing responses. In this study we describe the presence of functional axonal GABA receptors in cerebellar Purkinje cells by using a combination of direct patch-clamp recordings from the axon terminals and laser GABA photolysis. In Purkinje cells, axonal GABA receptors are depolarizing and induce an increase in neurotransmitter release that results in a change of short-term synaptic plasticity. These results contribute to our understanding of the cellular mechanisms of action of axonal GABA receptors and highlight the importance of the presynaptic compartment in neuronal computation. In neurons of the adult brain, somatodendritic GABA receptors (GABA Rs) mediate fast synaptic inhibition and play a crucial role in synaptic integration. GABA Rs are not only present in the somatodendritic compartment, but also in the axonal compartmen...

Axonal ionotropic receptors are present in a variety of neuronal types, and their function has largely been associated with the modulation of axonal activity and synaptic release. It is usually assumed that activation of axonal GABAARs comes from spillover, but in cerebellar molecular layer interneurons (MLIs) the GABA source is different: in these cells, GABA release activates presynaptic GABAA autoreceptors (autoRs) together with postsynaptic targets, producing an autoR-mediated synaptic event. The frequency of presynaptic, autoR-mediated miniature currents is twice that of their somatodendritic counterparts, suggesting that autoR-mediated responses have an important effect on interneuron activity. Here, we used local Ca(2+) photolysis in MLI axons of juvenile rats to evoke GABA release from individual varicosities to study the activation of axonal autoRs in single release sites. Our data show that single-site autoR conductances are similar to postsynaptic dendritic conductances. ...

Background: Studies involving chronic creatine supplementation in elite soccer players are scarce. Therefore, the aim of this study was to examine the effects of creatine monohydrate supplementation on lower-limb muscle power in Brazilian elite soccer players (n = 14 males) during pre-season training. Findings: This was a randomized, double-blind, placebo-controlled parallel-group study. Brazilian professional elite soccer players participated in this study. During the pre-season (7 weeks), all the subjects underwent a standardized physical and specific soccer training. Prior to and after either creatine monohydrate or placebo supplementation, the lower-limb muscle power was measured by countermovement jump performance. The Jumping performance was compared between groups at baseline (p = 0.99). After the intervention, jumping performance was lower in the placebo group (percent change = -0.7%; ES = -0.3) than in the creatine group (percent change = + 2.4%; ES = + 0.1), but it did not reach statistical significance (p = 0.23 for time x group interaction). Fisher's exact test revealed that the proportion of subjects that experienced a reduction in jumping performance was significantly greater in the placebo group than in the creatine group (5 and 1, respectively; p = 0.05) after the training. The magnitude-based inferences demonstrated that placebo resulted in a possible negative effect (50%) in jumping performance, whereas creatine supplementation led to a very likely trivial effect (96%) in jumping performance in the creatine group. Conclusions: Creatine monohydrate supplementation prevented the decrement in lower-limb muscle power in elite soccer players during a pre-season progressive training.

This work rationalizes the scalable synthesis of ultrasmall, ligand-free silicon nanomaterials via liquid-phase pulsed laser ablation process using picosecond pulses at ultraviolet wavelengths. Results showed that the irradiation time drives hydrodynamic NP size. Isolated, monodisperse Si-NPs are obtained at high yield (72%) using post-treatment process. The obtained Si-NPs have an average size of ∼10 nm (not aggregated) and display photoemission in the green spectral range. We directly characterized the ligand-free Si-NPs in a vertebrate animal (zebrafish) and assessed their toxicity during the development. In vivo assay revealed that Si-NPs are found inside in all the early life stages of embryos and larvae growth, showing that the biosafety of Si-NPs and malformation types are independent of the Si-NP dose. Si-NPs were directly imaged inside developing embryos by spinning disk-imaging technique with optical sectioning capability. We showed that Si-NPs can passively enter inside embryos by the pore canals of chorion, can diffuse in the circulatory system, i.e., blood vessel, and accumulate inside larvae midgut and yolk sac, and in the eye lens, indicating the crossing of the blood barrier.

This review re-evaluates the use of immunological probes to map enkephalinergic, dynorphinergic, and endorphinergic circuits in the CNS of lobe-finned fishes, ray-finned fishes, and cartilaginous fishes in light of the characterization of proenkephalin, prodynorphin, and POMC sequences from representatives of these groups of fish over the past 20 years. The use of a-MSH specific antisera is a reliable method for detecting POMC immunopositive cell bodies and fibers. Since a-MSH and b-endorphin are co-localized in the same neurons, these studies also reveal the distribution of endorphinergic networks. Met-enkephalin specific antisera can be used to detect enkephalinergic circuits in the CNS of gnathostomes because of the ubiquitous presence of this pentapeptide in the proenkephalin sequences of gnathostomes. However, the use of leu-enkephalin specific antisera to detect enkephalinergic networks is more problematic. While this immunological probe is appropriate for analyzing enkephalinergic networks in mammals and perhaps teleosts, for the lungfishes and cartilaginous fishes this probe is more likely able to detect dynorphinergic circuits. In this regard, there is a need to re-examine dynorphinergic networks in nonmammalian gnathostomes by using species specific antisera directed against dynorphin end-products.

Desaturase1 (desat1) is one of the few genes known to be involved in the two complementary aspects of sensory communicationsignal emission and signal receptionin Drosophila melanogaster. In particular, desat1 is necessary for the biosynthesis of major cuticular pheromones in both males and females. It is also involved in the male ability to discriminate sex pheromones. Each of these two sensory communication aspects depends on distinct desat1 putative regulatory regions. Here, we used (i) mutant alleles resulting from the insertion/excision of a transposable genomic element inserted in a desat1 regulatory region, and (ii) transgenics made with desat1 regulatory regions used to target desat1 RNAi. These genetic variants were used to study several reproduction-related phenotypes. In particular, we compared the fecundity of various mutant and transgenic desat1 females with regard to the developmental fate of their progeny. We also compared the mating performance in pairs of flies with altered desat1 expression in various desat1-expressing tissues together with their inability to disengage at the end of copulation. Moreover, we investigated the developmental origin of altered sex pheromone discrimination in male flies. We attempted to map some of the tissues involved in these reproduction-related phenotypes. Given that desat1 is expressed in many brain neurons and in nonneuronal tissues required for varied aspects of reproduction, our data suggest that the regulation of this gene has evolved to allow the optimal reproduction and a successful adaptation to varied environments in this cosmopolitan species.

We report on a novel Djungarian hamster mutant lineage that exhibits a loss of uncoupling protein (UCP) 3 mRNA and protein in brown adipose tissue (BAT), whereas UCP3 expression in skeletal muscle is only mildly diminished. In response to 2 d of cold exposure, UCP3 mRNA was 4.5-fold elevated in BAT of wild-type hamsters but remained undetectable in mutant hamsters. Notably, in BAT of warm-and cold-exposed mutant hamsters, UCP1 and UCP2 mRNA levels were increased. The tissue specificity of UCP3 deficiency suggests that the underlying unknown mutation impairs a factor controlling UCP3 gene expression selectively in brown adipocytes. In wildtype but not mutant primary brown adipocytes, UCP3 gene expression was stimulated by treatment with peroxisome proliferator activated receptor (PPAR) ligands. This implies that the underlying mutation causing UCP3 deficiency is expressed within brown adipocytes and disrupts PPAR-dependant transactivation of the UCP3 gene. On the functional level, we found no direct phenotypic consequences of altered UCP expression in BAT. The absence of UCP3 in BAT of cold-acclimated mutant hamsters affected neither maximal nonshivering thermogenesis elicited by noradrenaline nor the uncoupled respiration of isolated mitochondria in the presence of oligomycin and in response to palmitate.

The present results demonstrate that short daily cold exposures induce growth of brown adipose tissue (BAT) in mice. 2.5 h daily cold exposure has a similar effect on growth of BAT as a chronic exposure to the same low ambient temperature. 5 h daily cold exposure are an even more effective stimulus for growth of BAT. BAT cells from short daily cold exposed mice contain a small amount of cytoplasm and a large amount of fat, concentrated in a single fat vacuole, quite in contrast to the multilocular BAT cells from mice living at thermoneutrality or continuously in the cold. This suggests a different thermogenic function of BAT in short daily cold exposed mice, as compared with the role of BAT in chronically cold exposed mice.

isoquinolin-4-one, PQ) is a newly developed anthelmintic with a broad spectrum against trematodes and cestodes. Since Gtnnert and Andrews I report-ed antischistosomal effects of PQ, there have been many reports regarding the in vivo effects of this compound in animal 1-3 and clinical 4 8 experiments against trematodes such as Schistosoma mansoni '& 4, S. haematobium 2'5 S.japo-

In most studies aimed at localizing footprints of past selection, outliers at tails of the empirical distribution of a given test statistic are assumed to reflect locus-specific selective forces. Significance cutoffs are subjectively determined, rather than being related to a clear set of hypotheses. Here, we define an empirical p-value for the summary statistic by means of a permutation method that uses the observed SNP structure in the real data. To illustrate the methodology, we applied our approach to a panel of 2.9 million autosomal SNPs identified from re-sequencing a pool of 15 individuals from a brown egg layer line. We scanned the genome for local reductions in heterozygosity, suggestive of selective sweeps. We also employed a modified sliding window approach that accounts for gaps in the sequence and increases scanning resolution by moving the overlapping windows by steps of one SNP only, and suggest to call this a ''creeping window'' strategy. The approach confirmed selective sweeps in the region of previously described candidate genes, i.e. TSHR, PRL, PRLHR, INSR, LEPR, IGF1, and NRAMP1 when used as positive controls. The genome scan revealed 82 distinct regions with strong evidence of selection (genome-wide p-value,0.001), including genes known to be associated with eggshell structure and immune system such as CALB1 and GAL cluster, respectively. A substantial proportion of signals was found in poor gene content regions including the most extreme signal on chromosome 1. The observation of multiple signals in a highly selected layer line of chicken is consistent with the hypothesis that egg production is a complex trait controlled by many genes.

The rhodium(III)-catalyzed cross-coupling of (hetero)aryl nitrones with Morita-Baylis-Hillman (MBH) adducts is described. An allylated intermediate derived from aryl nitrones and MBH adducts allows the formation of bridged cyclic compounds via an exotype [3 + 2] cycloaddition. In sharp contrast, electron-rich indolinyl or aniline substrates were found to couple with MBH adducts to generate naphthalene or carbazole derivatives, respectively.

We investigated the effects of hypotonic saline-induced modifications of extracellular volume and sodium handling on the renal and metabolic response to amino acids (AA). Renal hemodynamics (Inutest, p-aminohippurate clearance), plasma AA, and glucagon levels, as well as urea and sodium excretion, were studied in seven adult volunteers infused for 2 h, on six separate occasions, according to the following protocols: 1) high-AA solution (300 mg ⋅ min−1⋅ 1.73 m−2); 2) low-AA solution (150 mg ⋅ min−1⋅ 1.73 m−2); 3) low AA + 2,000 ml/1.73 m2of 0.23% saline solution; 4) high AA + 0.23% saline; 5) high AA + 0.45% saline; and 6) 0.45% saline alone. The glomerular filtration rate (GFR) rise induced by the high-AA solution was similar to that induced by the low-AA solution (ΔGFR = +24 ± 6 and +20.2 ± 7 ml ⋅ min−1⋅ 1.73 m−2, respectively), whereas the plasma AA and glucagon levels and urea excretion rate increases were related to AA dose. The addition of 0.23% saline to the low-AA solution an...

The present paper reviews recent studies on changes in body mass, body composition and rates of energy expenditure during the breeding season in the black-legged Kittiwake (Rissa tridactyla) on Svalbard (79 8N). The main characteristic of the energy budget is a pronounced decrease in body mass as well as basal metabolic rate (BMR) after the eggs have hatched. While most internal organs lose mass in direct proportion to the general decrease in body mass, the liver and kidney masses decrease to a disproportionately greater extent. Since both the liver and the kidney have high intrinsic metabolic rates, these results support an earlier notion that the reduction in body mass is an adaptation to reduce maintenance costs. Alternatively, the reduced BMR is due to a decrease in energy uptake from the gastrointestinal tract, thereby ensuring that undigested food is ready to be regurgitated to the chicks. At the end of the chick-rearing period, the field metabolic rate (FMR) reaches its highest level, probably due to an increased workload associated with chick feeding. This occurs at a time of low body mass and BMR. A pronounced increase in the metabolic scope (FMRyBMR) during the latter part of the chick-rearing period demonstrates that BMR and FMR may change independently of each other and that the ratio FMRyBMR may not be a good measure of energy stress.

Attachment insecurity in the forms of attachment anxiety and avoidance is associated with mental disorders in humans. In this research field, rodents, especially mice and rats, are commonly used to study social behaviors and underlying biological mechanisms due to their pronounced sociability. However, quantitative assessment of attachment security/insecurity in rodents has been a major challenge. The present study identified attachment insecurity behaviors in rats subjected to maternal separation (MS) during postnatal days (PD) 2-16 and early weaning (EW) during PD 17-21. This MSEW procedure has been used to mimic early life neglect in humans. After MSEW, rats continued to survive until early adulthood when they were subjected to open-field, social interaction, and elevated-plus maze tests. Compared to CNT rats in either gender, MSEW rats moved longer distances at higher velocities in the open-field. The MSEW rats also showed lower ratios of travel distance at central zone over that on whole arena of the open-field compared to CNT rats. In social interaction test, male CNT rats preferred to investigate an empty cage than females; whereas female CNT rats spent more time with a partner-containing cage as compared to males. This gender-specific difference was reversed in MSEW rats. On elevated-plus maze female CNT rats exhibited more risk-taking behaviors as compared to male counterparts. Moreover, female MSEW rats experienced a greater difficulty in making a decision on whether approaching to or averting from which arms of elevated-plus maze. Taken together, male MSEW rats behaved like attachment anxiety while females' phenotype is alike to attachment avoidance described in humans. These results shall prompt further application of MSEW rat in abnormal psychology and biological psychiatry research.

Attachment insecurity in the forms of attachment anxiety and avoidance is associated with mental disorders in humans. In this research field, rodents, especially mice and rats, are commonly used to study social behaviors and underlying biological mechanisms due to their pronounced sociability. However, quantitative assessment of attachment security/insecurity in rodents has been a major challenge. The present study identified attachment insecurity behaviors in rats subjected to maternal separation (MS) during postnatal days (PD) 2–16 and early weaning (EW) during PD 17–21. This MSEW procedure has been used to mimic early life neglect in humans. After MSEW, rats continued to survive until early adulthood when they were subjected to open-field, social interaction, and elevated-plus maze tests. Compared to CNT rats in either gender, MSEW rats moved longer distances at higher velocities in the open-field. The MSEW rats also showed lower ratios of travel distance at central zone over tha...

Study design, materials and methods Since February 2004, a fistula treatment program developed by the Eritrean Ministry of Health, the Eritrean Women's Project and the United Nations Population Fund (UNFPA) has treated over 600 cases of obstetric fistula. During this time period, we have performed 50 Mainz II pouches (48 cases of irreparable fistula and 2 cases of bladder extrophy). On our most recent trip (February 2012), we reviewed the charts of all 50 diversion patients, focusing on the occurrence of known long-term complications of urinary diversion: infections, renal function, and metabolic acidosis.

Key points Central sleep apnoea is a condition characterized by oscillations between apnoea and hyperpnoea during sleep, which can have many serous health implications. Each ventilatory overshoot following an apnoea attenuates peripheral chemoreceptor input which, in turn, has the potential to cause a further apnoea. In a decerebrate, vagotomized, in situ rat preparation, we show that central apnoeas can be overcome both physiologically (with high peripheral CO2) and pharmacologically (with peripheral pituitary adenylate cyclase‐activating peptide). We also show that the central apnoeic threshold, i.e. the CO2 level at which the animal stops breathing, can be lowered by increasing peripheral chemoreceptor stimulation. These data suggest that stimulation of peripheral chemoreceptors may prevent central apnoeas, re‐affirming the peripheral chemoreceptors as possible therapeutic targets for some sleep apnea phenotypes.   Central sleep apnoea is a condition characterized by oscillations...

Methods The prospective, randomized trial was performed ın preterm infants who were hospitalized in the NICU at Baskent University Ankara Hospital between January 2011 and February 2012. A total of 51 infants were enrolled and randomly assigned to one of two groups: Group 1 (n=27) received probiotic therapy and Group 2 (n=24) did not receive probiotics. The probiotic used was Lactobacillus reuteri (Biogaia® AB, Sweden). Subjects underwent weekly nasal swab and stool cultures for a maxımum of 6 weeks, and at the tıme of dıscharge ıf thıs was prıor to 6 weeks. All posıtıve cultures were further tested for culture-specıfıc ıdentıfıcatıon and antıbıotıc suceptibility.

This paper presents a unifying synthesis of Möbius Collapse Logic (MCL) and the Entropic Resonance (ER) framework within the broader ontology of Omniological Resonance Theory (ORT). MCL models computation through recursive topological collapse structures driven by resonance weight hierarchies, while ER grounds physical and symbolic systems in entropy-governed resonance cascades mapped onto prime-number Hilbert spaces. We demonstrate that MCL's Möbius-based self-transformations are isomorphic to the symbolic phase inversions of ER when mapped through ORT's nested resonance architecture. The fusion yields a complete transdisciplinary model of computation, consciousness, and reality wherein quantum coherence, prime resonance, and topological recursion converge to form a testable substrate for universal field behavior.

La extracción de terceros molares impactados es uno de los procedimientos más comunes realizados por cirujanos maxilofaciales. Predecir la dificultad quirúrgica, a través del análisis de Arch Hosp Univ "Gen Calixto García" Este es un artículo en Acceso Abierto distribuido según los términos de la Licencia Creative Commons Atribución-No Comercial 4.0 que permite el uso, distribución y reproducción no comerciales y sin restricciones en cualquier medio, siempre que sea debidamente citada la fuente primaria de publicación.

Local field potentials (LFPs) capture the electrical activity produced by principal cells during integration of converging synaptic inputs from multiple neuronal populations. However, since synaptic currents mix in the extracellular volume, LFPs have complex spatiotemporal structure, making them hard to exploit. Here we propose a biophysical framework to identify and separate LFP-generators. First we use a computational multineuronal model that scales up single cell electrogenesis driven by several synaptic inputs to realistic aggregate LFPs. This approach relies on the fixed but distinct locations of synaptic inputs from different presynaptic populations targeting a laminated brain structure. Thus the LFPs are contributed by several pathway-specific LFP-generators, whose electrical activity is defined by the spatial distribution of synaptic terminals and the time course of synaptic currents initiated in target cells by the corresponding presynaptic population. Then we explore the efficacy of independent component analysis to blindly separate converging sources and reconstruct pathway-specific LFP-generators. This approach can optimally locate synaptic inputs with subcellular accuracy while the reconstructed time course of pathway-specific LFP-generators is reliable in the millisecond scale. We also describe few cases where the non-linear intracellular interaction of strongly overlapping LFP-generators may lead to a significant cross-contamination and the appearance of derivative generators. We show that the approach reliably disentangle ongoing LFPs in the hippocampus into contribution of several LFP-generators. We were able to readout in parallel the pathway-specific presynaptic activity of projection cells in the entorhinal cortex and pyramidal cells in the ipsilateral and contralateral CA3. Thus we provide formal mathematical and experimental support for parallel readout of the activity of converging presynaptic populations in working neuronal circuits from common LFPs.

Obesity is considered a high-risk disease and a global epidemic, and the number of obese patients is rising at an alarming rate worldwide. High-fat diet-induced dysbiosis of the intestinal microbiota is considered an essential factor related to obesity. Bariatric surgery induces a sharp decrease in fat content and effectively improves the metabolism of obese individuals. Herein, we aimed to investigate the effects of a high-fat diet-induced obesity and the alterations in gastric and intestinal microbiota resulting from sleeve gastrectomy on clinical outcomes. We performed 16S sequencing of gastric and fecal samples obtained from rats in three treatment groups: normal chow diet, high-fat diet (HFD), and sleeve gastrectomy after HDF for 14 weeks. The area under the curve of fasting glucose and the levels of leptin and low-density lipoproteins were significantly different between groups. Microbial taxa that were highly correlated with several clinical parameters were identified for each group. Glyoxylate and dicarboxylate, taurine and hypotaurine, butanoate, nitrogen, and pyrimidine metabolism and aminoacyl-transfer ribonucleic acid biosynthesis were affected by bariatric surgery and were significantly associated with changes in the composition of gastric and fecal microbiomes. Connectivity and co-occurrence were higher in fecal samples than in gastric tissues. Our results elucidated the positive effects of sleeve gastrectomy in obesity and shed light on changes in the microbiomes of gastric and fecal samples.

function (six-minute walk test, quick motor function test), daily life activities (Rasch-build Pompe-specific Activity scale (R-PAct)), and pulmonary function (forced vital capacity (FVC) in upright and supine positions, maximum inspiratory (MIP), and expiratory (MEP) pressures) at 3-6 months intervals before and after start of ERT. We used linear mixed-effects models for repeated measures to compare patients' outcomes at 5 years of treatment with the extrapolated natural course of the disease. We included 102 adult Pompe patients. Median follow-up before treatment (natural-course period) was 1.1 years; during the treatment 5 years. Relative to the extrapolated natural disease course, treated patients had better muscle strength (MRC sum-score +6.6 percentage points (pp); HHD sum-score +9.6 pp; both p < 0.0001), activity levels (R-PAct +10.8 pp, p < 0.002), and pulmonary function (FVC in upright position +7.3 pp; FVC in supine position +7.6 pp; MIP +20.8 pp; MEP +17.3 pp; all p < 0.005). Relative to start of treatment, the median distance walked improved (376 vs 416 meters; p = 0.03). Most outcome measures showed an improvement during the first two to three years of treatment followed by a plateau or slight decline. Response to treatment was similar between groups, irrespective of gender, age, or disease duration. Long-term treatment with ERT positively affects muscle strength, pulmonary function and daily life activities in adult Pompe patients, with a peak effect around two to three years of treatment.

Background Little is known about the association of dietary patterns with thyroid function. Since thyroid function and cardiometabolic variables are inter-related, we investigated whether cardiometabolic-related dietary patterns are associated with thyroid function. This cross-sectional study included 3520 Tehran Lipid and Glucose Study participants. Reduced rank regression was used to find dietary patterns with body mass index, serum fasting glucose, triglycerides, HDL-C, and systolic and diastolic blood pressures as response variables. Two patterns were retained, one based on 35 food groups (native-based pattern) and the other based on the European Prospective Investigation into Cancer and Nutrition Germany (EPIC) food grouping (n = 33). A confirmatory cardio-metabolic dietary pattern was also created according to the weight of food groups proposed by the Framingham Offspring Study (FOS). The association of each pattern with thyroid-stimulating hormone (TSH), free thyroxine, and thyroid peroxidase antibody (TPOAb) and the odds of thyroid dysfunction was examined by linear and logistic regression, respectively. The two exploratory dietary patterns were highly correlated and associated with greater TSH levels in euthyroid participants. The adjusted odds ratio (95% CI) of subclinical hypothyroidism per one standard deviation was 1.14 (1.01, 1.28) for the native-based pattern and 1.16 (1.03, 1.31) for the EPIC-based pattern. The odds of subclinical hypothyroidism was significantly greater in the second and third tertiles of the native-based pattern compared to the first tertile in the adjusted model (p-trend = 0.005). The odds of subclinical hypothyroidism increased across the tertiles of the EPIC-based pattern, but the odds was significantly higher only in tertile 3 compared to tertile 1, with an OR (95% CI) of 1.44 (1.07, 1.94) in the adjusted model. The adjusted odds of clinical hypothyroidism were greater in tertile 3 of the native-based pattern compared with tertile 1 (OR = 1.65, 95% CI 1.04, 2.62). The patterns were unrelated to hyperthyroidism or TPOAb positivity. The FOS-based confirmatory score was unrelated to thyroid function. Conclusions A diet high in fast foods, soft drinks, and legumes and low in confectionery, potatoes, butter, and jam and honey was associated with higher TSH levels in euthyroidism and higher odds of subclinical hypothyroidism.

The histological makeup of the pancreas in immature male and female Iraqi blackbuck (Caprus hircus) has not been well described. We aimed to describe the histological features of the pancreas in immature male and female Iraqi blackbuck. Samples were collected from 20 immature male and female animals' pancreas, obtained from the Al-Najaf slaughterhouse. The samples were fixed in 10% neutral buffered formalin, processed using standard histological methods, and stained with Gomori's, weigart's, Harris hematoxylin, eosin, and maldonad's stains (LOBA Chemie laboratory reagents and fine chemicals). The study showed that the goblet cells were underdeveloped and crowded, while the centroacinar cell's position and characteristics might indicate that these cells are involved in the transport of fluids and secretions within the duct system. The mean distribution of the total number of Langerhans islets' cells was similar across all groups (males and females), with no discernible variances. Morphometric analysis of the Langerhans islets revealed no differences in the distribution of islets between any of the studied groups in the right, left, or body of the pancreas. The histological analysis of the pancreas in immature male and female Iraqi blackbuck showed unique features regarding the arrangement of the islets of Langerhans, goblet cells, and centroacinar cells. These findings could contribute to a better understanding of the physiology and pathology of the pancreas in this species.

Background: Some experimental and human data suggest that exposure to polychlorinated biphenyls (PCBs) may induce ototoxicity, though results of previous epidemiologic studies are mixed and generally focus on either prenatal or postnatal PCB concentrations exclusively. oBjectives: Our aim was to evaluate the association between pre-and postnatal PCB concentrations in relation to cochlear status, assessed by distortion product otoacoustic emissions (DPOAEs), and to further clarify the critical periods in development where cochlear status may be most susceptible to PCBs. Methods: A total of 351 children from a birth cohort in eastern Slovakia underwent otoacoustic testing at 45 months of age. Maternal pregnancy, cord, and child 6-, 16-, and 45-month blood samples were collected and analyzed for PCB concentrations. At 45 months of age, DPOAEs were assessed at 11 frequencies in both ears. Multivariate, generalized linear models were used to estimate the associations between PCB concentrations at different ages and DPOAEs, adjusting for potential confounders. results: Maternal and cord PCB-153 concentrations were not associated with DPOAEs at 45 months. Higher postnatal PCB concentrations at 6-, 16-, and 45-months of age were associated with lower (poorer) DPOAE amplitudes. When all postnatal PCB exposures were considered as an area-under-the-curve metric, an increase in PCB-153 concentration from the 25th to the 75th percentile was associated with a 1.6-dB SPL (sound pressure level) decrease in DPOAE amplitude (95% CI: -2.6, -0.5; p = 0.003). conclusions: In this study, postnatal rather than maternal or cord PCB concentrations were associated with poorer performance on otoacoustic tests at age 45 months.

Miniaturization is recurrent in tetrapods, and has been widely recognized to be an evolutionary process resulting from the occupation of previously unexploited niches (Hanken and Wake, 1993; Rieppel, 1984a, 1996). In this thesis I review the process of miniaturization and its effects on the skull of squamates (lizards, snakes, and amphisbaenians). I compiled a list of characteristics previously described for squamates and summarized the main differences among higher level groups (e.g., Iguania, Gekkota or Scincomorpha). I also investigated whether observed traits linked to miniaturization are the product of convergent evolution. I used a large published morphological data set that includes 204 species of which 54 are miniaturized. I coded characters for an additional species that represent the smallest known squamates (e.g., Sphaerodactylus ariasae and Brookesia micra) and belong to taxonomic groups with minor representation in the original dataset. Analyses identified two character...

1. Local conductance changes produced by various bath-applied agonists at frog end-plate membrane were measured using focal recording of extracellular potential in voltage-clamped muscle fibres. The potential difference between a focal micro- pipette placed on the nerve terminal and another micro-pipette placed on or near inactive membrane was taken as proportional to the agonist-induced current through a small patch of end-plate membrane.

1. Glutamate receptor (GluR) channels were studied in basket cells in the dentate gyrus of rat hippocampal slices. Basket cells were identified by their location, dendritic morphology and high frequency of action potentials generated during sustained current injection. 2. Dual-component currents were activated by fast application of glutamate to outside-out membrane patches isolated from basket cell somata (10 /SM glycine, no external Mg2+). The fast component was selectively blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), the slow component by D-2-amino-5-phosphonopentanoic acid (D-AP5). This suggests that the two components were mediated by a-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor (AMPAR)/kainate receptor and N-methyl-D-aspartate receptor (NMDAR) channels, respectively. The mean ratio of the peak current of the NMDAR component to that of the AMPAR/kainate receptor component was 0-22 (1 ms pulses of 10 mm glutamate). 3. The AMPAR/kainate receptor component, which was studied in isolation in the presence of D-AP5, was identified as AMPAR mediated on the basis of the preferential activation by AMPA as compared with kainate, the weak desensitization of kainate-activated currents, the cross-desensitization between AMPA and kainate, and the reduction of desensitization by cyclothiazide. 4. Deactivation of basket cell AMPARs following 1 ms pulses of glutamate occurred with a time constant (T) of 1-2 + 0 1 ms (mean + S.E.M.). During 100 ms glutamate pulses, AMPARs desensitized with a r of 3.7 + 0-2 ms. 5. The peak current-voltage (I-V) relation of AMPAR-mediated currents in Na+-rich extracellular solution showed a reversal potential of -4 0 + 2-6 mV and was characterized by a doubly rectifying shape. The conductance of single AMPAR channels was estimated as 22-6 + 1 6 pS using non-stationary fluctuation analysis. AMPARs expressed in hippocampal basket cells were highly Ca2+ permeable (Pca/PK = 1-79). 6. NMDARs in hippocampal basket cells were studied in isolation in the presence of CNQX. Deactivation of NMDARs activated by glutamate pulses occurred bi-exponentially with mean r values of 266 + 23 ms (76 %) and 2620 + 383 ms (24 %). 7. The peak I-V relation of the NMDAR-mediated component in Na+-rich extracellular solution showed a reversal potential of 1.5 + 0-6 mV and a region of negative slope at negative membrane potentials in the presence of external Mg2+, due to voltage-dependent block by these ions. The conductance of single NMDAR channels in the main open state was 50-2 + 1.8 pS. NMDARs in hippocampal basket cells were highly permeable to Ca2P (Pca/PK = 6 68). 8. AMPARs in hippocampal basket cells are characterized by about threefold faster kinetics and twentyfold higher Ca2P permeability than AMPARs in hippocampal granule or pyramidal cells. Simulations show that the Ca2P influx through basket cell AMPARs is comparable to that through NMDARs at negative membrane potentials with physiological concentrations of Ca2P and Mg2+. This suggests a dual pathway of synaptically mediated Ca2P entry into interneurones. * To whom correspondence should be addressed. 3674 Glutamate receptors in hippocampal interneurones Glutamate, the major excitatory neurotransmitter in the mammalian central nervous system (CNS), mediates synaptic transmission by acting on a-amino-3-hydroxy-5methyl-4-isoxazolepropionate (AMPA)or kainate-type and N-methyl-D-aspartate (NMDA)-type glutamate receptor (GluR) channels . At many synapses AMPA/kainate and NMDA receptors are colocalized and coactivated by synaptically released glutamate (Jonas & Spruston, 1994). Determining the Ca2! permeability of these receptors is important for the understanding of excitatory synaptic transmission in the CNS, since Ca2' is an intracellular second messenger and triggers long-lasting changes in synaptic efficacy, e.g. long- term potentiation (LTP; Bliss & Collingridge, 1993). AMPA/kainate-type GluRs are thought to be weakly permeable to CaP, whereas the Ca2+ permeability of

Sensory stimuli are encoded differently across cortical layers and it is unknown how response characteristics relate to the morphological identity of responding cells. We therefore juxtasomally recorded action potential (AP) patterns from excitatory cells in layer (L) 2/3, L4, L5 and L6 of rat barrel cortex in response to a standard stimulus (e.g. repeated deflection of single whiskers in the caudal direction). Subsequent single-cell filling with biocytin allowed for post hoc identification of recorded cells. We report three major conclusions. First, sensory-evoked responses were layerand cell-type-specific but always < 1 AP per stimulus, indicating low AP rates for the entire cortical column. Second, response latencies from L4, L5B and L6 were comparable and thus a whisker deflection is initially represented simultaneously in these layers. Finally, L5 thick-tufted cells dominated the cortical AP output following sensory stimulation, suggesting that these cells could direct sensory guided behaviours.

I. Frog cutaneous pectoris nerve-muscle preparations were incubated with collagenase and protease and examined with electrophysiological and electron microscopic techniques. 2. The physiological properties and intracellular ultrastructural ap- pearance of individual muscle and nerve cells were not affected by the enzyme treatment. However, neuromuscular transmission and the mor- phology of the nerve-muscle junction were altered. 3. Collagenase produced an irreversible loss of activity of end-plate cholinesterase and a partial loss of stainable 'synaptic cleft material'. 4. Protease produced these changes and, in addition, the entire base- ment membrane was digested, which led to 'synaptic disjunction' of nerve terminals and muscle end-plates.

Direct stimulation of cultured diaphragm strips in a pattern similar to breathing for 7-8 days at an average rate of 10-12/sec (or 5/sec in some experiments), resulted in a marked reduction (about 95 % in experiments at 10/sec) in extrajunctional sensitivity to ionophoretically applied ACh. 9. Direct stimulation for 24 hr at 10/sec (comparable to a period of spontaneous activity) caused only a small reduction in extrajunctional ACh-sensitivity. 10. We conclude that spontaneous activity in single fibres under these conditions occurs cyclically because activity, over a period of hours, inhibits the ability of the fibrillating fibre to initiate further action poten- tials. Repeated self-inhibition of spontaneous activity probably explains why denervated muscle fibres remain highly sensitive to extrajunctionally applied ACh.

1. Inward currents through single K+ channels in isolated ventricular heart cells of the guinea-pig were recorded using the patch-clamp techhi-que(Hamill, Marty, Neher, Sakmann & Sigworth, 1981). The voltage-dependent gating properties of the channels were examined in the potential range between 0 and -120 mV with 145 mM-KCl on the extracellular side of the membrane patch, i.e. with approximately symmetrical transmembrane K+ concentrations. 2. When voltage pulses from 0 mV to negative test potentials were applied to patches containing several channels, more channels were open at the beginning of the pulses than in the steady state. Averages of many current responses showed inactivation of the mean current in response to the hyperpolarizing voltage pulses. The inactivation was stronger and faster at larger hyperpolarization. 3. The lifetimes of the open and closed states of the channel and the probability of the open state p were estimated from records of the elementary currents at various constant potentials. As indicated by the inactivation of the averaged currents, the value of p was smaller at more negative potentials, approximately 0 15 at -50 mV and 0-02 at -110 mV. This caused a negative slope in the current-voltage relation of the time-averaged current at potentials more negative than -50 mV. 4. The channel openings were grouped in complex bursts. At least three exponentials were needed to fit the frequency histogram of the lifetimes of all closed states (time constants at -50 mV: 1-1 ms, 16 ms and 3-2 s). The lifetimes of the individual openings were exponentially distributed (time constant: 70 ms). 5. The kinetics of the channel were interpreted by two different models involving three states of a channel (closed-closed-open or closed-open-closed). The rate constants and their voltage dependence were estimated for both models. Both models describe the data equally well; the reason for this ambiguity is discussed. 6. The channels are blocked by Cs+ or Ba2+. Cs+ (0.1 mM) caused frequent and short interruptions of the individual channel openings. Ba2+ (0-5 mM) also shortened the openings and in addition decreased the number of openings per burst. t To whom correspondence should be addressed. Same address as B. S. (*) after December 31, 1983. B. SAKMANN AND G. TRUBE 7. The results suggest that the inward-rectifying current IKI in heart ventricular cells is partially inactivated by hyperpolarization. The inactivation could account for part of the time-dependent decrease in the whole-cell current previously ascribed to depletion of K+.

1. Excitatory postsynaptic currents (EPSCs) were recorded in CA3 pyramidal cells of hippocampal slices of 15-to 24-day-old rats (22 °C) using the whole-cell configuration of the patch clamp technique. 2. Composite EPSCs were evoked by extracellular stimulation of the mossy fibre tract. Using the selective blockers 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and D-2-amino-5-phosphonopentanoic acid (APV), a major o-amino-3-hydroxy-5methylisoxazole-4-propionate (AMPA)/kainate receptor-mediated component and a minor NMDA receptor-mediated component with slower time course were dis- tinguished. For the AMPA/kainate receptor-mediated component, the peak current-voltage (I-V) relation was linear, with a reversal potential close to 0 mV. The half-maximal blocking concentration of CNQX was 353 nm. 3. Unitary EPSCs of the mossy fibre terminal (MF)-CA3 pyramidal cell synapse were evoked at membrane potentials of -70 to -90 mV by low-intensity extracellular stimulation of granule cell somata using fine-tipped pipettes. The EPSC peak amplitude as a function of stimulus intensity showed all-or-none behaviour. The region of low threshold was restricted to a few micrometres. This suggests that extracellular stimulation was focal, and that the stimulus-evoked EPSCs were unitary. 4. Latency and rise time histograms of EPSCs evoked by granule cell stimulation showed narrow unimodal distributions within each experiment. The mean latency was 4-2 + 1I0 ms, and the mean 20-80 % rise time was 0-6 + 0X1 ms (23 cells). When fitted within the range 0 7 ms to 20 ms after the peak, the decay of the EPSCs with the fastest rise (rise time 0 5 ms or less) could be described by a single exponential function; the mean time constant was in the range 30-6 6 ms with a mean of 4-8 ms (8 cells). 5. Peak amplitudes of the EPSCs evoked by suprathreshold granule cell stimulation fluctuated between trials. The apparent EPSC peak conductance in normal extracellular solution (2 mm Ca2+, 1 mM Mg2+), excluding failures, was 1 nS. Reducing the Ca2`concentration and increasing the Mg2+ concentration reduced the mean peak amplitude in a concentration-dependent manner. 6. Peaks in EPSC peak amplitude distributions were apparent in low MS 2022 21-2 P. JONAS, G. MAJOR AND B. SAKMANN Ca2`and high Mg2+. Using the criteria of equidistance and the presence of peaks and dips in the autocorrelation function, five of nine EPSC peak amplitude distributions were judged to be quantal. From the likelihood ratio when fitting non-quantal and quantal model functions to the peak current data, the probability of wrongly rejecting the non-quantal models was estimated to be in the range < 0 001-9 4%. The apparent quantal conductance change was in the range 105-177 pS with a mean of 133 pS in different experiments. The coefficient of variation of a quantal event was estimated to be 22 %. 7. Spontaneously occurring miniature EPSCs were recorded at negative mem- brane potentials in the presence of 1 ,UM tetrodotoxin (TTX). Miniature EPSC 20-80% rise times varied between 0-2 and > 10 ms within each experiment. Peak amplitude distributions of the miniature EPSCs with rise times less than 0-8 ms (presumably arising from MF-CA3 synapses) were skewed. Mode and mean values of these distributions corresponded to apparent conductances of 106 + 19 and 251 + 22 pS, respectively (6 cells). 8. Fast application of 1-3 mm glutamate to outside-out patches isolated from the somata of CA3 pyramidal cells activated currents which were mediated by AMPA/kainate receptor channels. The elementary conductance of these channels estimated from non-stationary fluctuation analysis was 8-5 + 2-1 pS (9 patches), and the maximal open probability with 3 mm glutamate was 0-71 +0-06. Extracellular divalent cation concentrations had only small effects on the recorded glutamateactivated currents. 9. In the whole-cell recording configuration, responses to short current pulses and a biocytin fill were obtained from a CA3 pyramidal neurone. A compartmental model was made, based on the cell morphology as reconstructed using a light microscope. The electrical parameters of the model were adjusted until its short pulse response gave the best fit to the measured response of the neurone. This gave a specific membrane capacitance (Cm) of 0-683 ,tF cm-2, a specific membrane resistance (Rm) of 164000 Q cm2, and a cytoplasmic resistivity (Ri) of 294 Q cm, with zero somatic shunt conductance. 10. The most proximal and the most distal mossy fibre synaptic conductances were simulated, with the soma voltage clamped via different series resistances. Both the dendritic cable and the series resistance attenuated and slowed the EPSCs. With the plausible range of series resistances (1-5-10 MQ), the apparent peak conductance was reduced to 0 32-0{87 of the 'real' value, the 20-80 % rise time was increased by a factor of 1-2-4-5 and the effective decay time constant by a factor of 1-1-2-6. 11. The results indicate that unitary EPSCs of MF-CA3 synapses show a rapid rise and a fast decay, and that they are quantal in nature, at least in a subset of MF-CA3 synapses. We estimate that a typical unitary EPSC of the MF-CA3 synapse at a 'physiological' concentration of divalent cations has a quantal content between 2 and 16. Considering voltage clamp errors, a quantal event appears to be generated by the simultaneous opening of between fourteen and sixty-five glutamate receptor channels of the AMPA/kainate subtype.

Whereas the mechanisms underlying the association of toxic dietary xenobiotics and cancer risk are not well established, it is plausible that dietary pattern may affect the colon environment by enhancing or reducing exposure to mutagens. This work aimed to investigate the association between xenobiotics intake and different stages of intestinal mucosal damage and colorectal cancer (CRC) screening and examine whether these associations may be mediated by altered intestinal mutagenicity. This was a case control study with 37 control subjects, 49 patients diagnosed with intestinal polyps, and 7 diagnosed with CRC. Lifestyle, dietary, and clinical information was registered after colonoscopy. For xenobiotics intake estimation the European Prospective Investigation into Cancer (EPIC) and the Computerized Heterocyclic Amines Resource for Research in Epidemiology of Disease (CHARRED) databases were used. The mutagenicity of fecal supernatants was assayed by the Ames test and light microsco...

When aquatic reptiles, birds and mammals submerge, they typically exhibit a dive response in which breathing ceases, heart rate slows, and blood flow to peripheral tissues is reduced. The profound dive response that occurs during forced submergence sequesters blood oxygen for the brain and heart while allowing peripheral tissues to become anaerobic, thus protecting the animal from immediate asphyxiation. However, the decrease in peripheral blood flow is in direct conflict with the exercise response necessary for supporting muscle metabolism during submerged swimming. In free diving animals, a dive response still occurs, but it is less intense than during forced submergence, and whole-body metabolism remains aerobic. If blood oxygen is not sequestered for brain and heart metabolism during normal diving, then what is the purpose of the dive response? Here, we show that its primary role may be to regulate the degree of hypoxia in skeletal muscle so that blood and muscle oxygen stores can be efficiently used. Paradoxically, the muscles of diving vertebrates must become hypoxic to maximize aerobic dive duration. At the same time, morphological and enzymatic adaptations enhance intracellular oxygen diffusion at low partial pressures of oxygen. Optimizing the use of blood and muscle oxygen stores allows aquatic, air-breathing vertebrates to exercise for prolonged periods while holding their breath.

Ferrocement is a composite used as a construction material. For any construction material, one of the crucial parameters considered during design is flexural and impact strength. This study’s objective was to look at how ribbed ferrocement panels behave when subjected to flexural and impact loads. The goal of this work was to determine how panel thickness and volume proportion of mesh affect the flexural and impact strength of ribbed ferrocement panels through an experimental and analytical programme. The experimental work consists of the preparation of ferrocement panels with 20mm, 30mm, and 40 mm thicknesses. For the preparation of the specimens, a matrix with a strength of 40 MPa and a mix proportion of cement and sand was 1:1.75 with a water-cement ratio of 0.40 was utilized. The specimens were reinforced with welded square wire mesh for a volume proportion of mesh between 1.5% to 2% for different sizes. These specimens were tested under two-point flexural loading and drop-weigh...

Background The aim of the present study was to investigate the role of progesterone on the developmental competence of cumulus-oocyte complexes (COCs) and cumulus-denuded oocytes (CDOs) at germinal vesicle (GV) stage. Materials and methods GV oocytes of pregnant mare&#39;s serum gonadotropin (PMSG)-primed prepubertal mice were divided into two groups: CDOs and COCs. The oocytes were cultured in TCM199 with different concentrations of progesterone (10, 38, 50 and 100 μM) and without progesterone (controls). The number of oocytes at the GV, germinal vesicle breakdown (GVBD) and metaphase II (MII) stages were counted. In vitro fertilization (IVF) of MII oocytes and their development to the blastocyst stage were evaluated. Results Significantly different MII rates were observed between the COCs (85%) and CDOs (68%) control groups. The MII rates of 83%, 48%, 14% and 0% for COCs and 65%, 53%, 20% and 0% for CDOs were obtained in TCM199 that contained 10, 38, 50 and 100μM progesterone conc...

The aim of this study was to evaluate the effects of progesterone and ovarian stimulation on the development and implantation rate of mouse embryos. Two-cell embryos were collected from superovulated mice and cultured in the presence of different concentrations of progesterone (0, 5, 10 and 20 ng/ml). Also other mice were rendered pregnant in unstimulated, unstimulated progesterone-injected, superovulated and superovulated progesterone-injected groups to collect the blastocysts. The number of blastocysts and implantation sites were recorded on the 4th and 7th day of pregnancy, respectively. The diameter and cell number of blastocysts were analyzed in the in vitro and in vivo groups. After 120 h culture, the percentage of hatched blastocyst embryos in control and 5, 10 and 20 ng/ml progesterone-injected groups were 63.9%, 64.2%, 64.2% and 75.6% respectively. There were significant differences between the developmental rates of embryos in the presence of 20 ng/ml progesterone and the control and other concentrations of progesteroneinjected groups (P≤0.001). The in vivo blastocyst survival rate (97.68%) and implantation rate (92.06%) in the unstimulated and progesterone-injected groups were higher than in the other groups. Blastocyst cell numbers in the superovulated (128.62 ± 1.30) and superovulated progesterone-injected groups (126.88 ± 1.60) were significantly different from the control (P<0.001). The progesterone injection without ovarian induction improved the embryo survival and implantation rates, but after superovulation it did not ameliorate the negative effects of superovulation on the implantation rate.