International journal of physiology, pathophysiology and pharmacology最新文献

Background: Impaired cognitive flexibility is the core manifestation of schizophrenia (SZ). Previous literature raised a claim against the effect of atypical antipsychotic drugs (AAD) on cognitive and executive functions whose cause needs further investigation. Attention set-shifting task (ASST) tests the prefrontal cortex's (PFC) executive and flexibility functions.

Goals: To examine Olanzapine (OLZ) effect on ASST, expression of N-methyl-D-aspartate receptor 1 (NMDR-NR1) in prefrontal cortex (PFC), and metabolic comorbidity in ketamine (KET) model of SZ.

Methods: Sixty-two male rats were divided into three groups: 8 for ASST and 30 for open field, ELISA and immunohistochemistry sub-chronic study, and 24 for regular serological and histopathological examination. Rats treated with V: vehicle; K: KET and KO: OLZ plus KET.

Results: KET caused significant increase in time, trials, and errors to reach criterion. OLZ co-administration reversed effects of KET in ASST with no reduction of locomotor activity. OLZ normalized KET-induced rise of NR1 expression and protected against KET-induced degenerative changes in hippocampus and PFC. Significant increase in serum liver enzymes, total bilirubin, and lipids with chronic compared to sub-chronic OLZ administration. In contrast, insignificant difference between sub-chronic OLZ and vehicle was found.

Conclusions: Current study demonstrated the efficacy of OLZ to reverse KET-induced cognitive deficits in ASST with neither reduction in NR1 expression in PFC nor metabolic malfunction in the sub-chronic study. It also showed the protective effect of OLZ on KET induced neuronal degeneration and necrosis. We suggest that chronic OLZ treatment-induced-metabolic malfunction might be the cause of time-dependent cognitive deterioration.

Association of organ sizes in the genitalia have long been a topic of interest for the general public. However, factors such as selection bias, embarrassment, and invasive testing have hindered studies on living individuals. We obtained measurements of penile size, testicular weight, and prostate weight, and conducted related serum testing on 63 Japanese male adults who died of unexpected reasons and underwent autopsy from 2009 to 2013. Micropenis was seen in 7 subjects (11.1%) as determined by flaccid penile length. Penile measurements were mainly correlated with body weight, testicular weight with age and body mass index, and prostate weight with age and serum prostate-specific antigen level. No correlation was detected between testosterone and any genital organ measurements. Interestingly, penile circumference showed no correlation to any of the penile length measurements. Prostate weight showed a significant positive correlation with penile circumference, penile stretched length, and testicular weight. Although the direct clinical implications are unclear, utilizing autopsy provided insight into genital organ measurements free of patient selection bias and other disadvantages of live patient testing. With a larger sample size, autopsy studies may be of use to future adjustment of nomograms.

Heavy metal mixture can induce multiple organ damage through oxidative stress and inflammatory processes. Dietary intervention using natural antidotes in resource poor countries where classical metal chelators are either not affordable or available can be explored as an alternative means of management of public health effects of chronic heavy metal exposure. The search for natural antidote against the deleterious effects of heavy metals gives the thrust for this study. Thus, the study investigated the effect of aqueous leaf extract of Costus afer on liver, kidney, brain and testis induced by low dose heavy metal mixture (LDHMM) of PbCl₂, CdCl₂ and HgCl₂ of concentrations of 20 mg/kg, 1.61 mg/kg and 0.40 mg/kg, respectively. Five groups of seven rats each (weight-matched) were used. First and second groups received deionized water and heavy metal mixture and served as normal and toxic controls, respectively. Groups 3, 4 and 5 received through oral gavage 750, 1500, 2250 mg/kg of the Costus afer extract respectively, with the metal mixture concurrently. All treatments were four times a week for 90 days (4/week/90 days). Hepatorenal, hormonal, oxidative stress markers, cytokines (interleukin-6 and interleukin-10), and heavy metals (Pb, Cd and Hg) concentrations were assayed. The one-way analysis of variance, agglomerative hierarchical clustering, parallel coordinates plot, principal component analysis and Bray Curtis dissimilarity were used to statistically analyze the data. LDHMM caused significant changes in these organs and however, the plant extract provided a protective effect against these pathological changes. The statistical analysis revealed that the kidney was the most affected organ, followed by the liver, then brain and testis, respectively. Costus afer may be an important nutraceutical in multi-organ deleterious effects of LDHMM following its regulation of oxidative stress markers, inflammatory cytokines and biometal chelation.

NMDA receptors (NMDARs) are ion channels gated by glutamate, the major excitatory neurotransmitter in the central nervous system. Anti-NMDA receptor (anti-NMDAR) encephalitis is an autoimmune disease characterized by the presence of autoantibodies against the NMDAR GluN1 subunit. Here we briefly review current advances in the understanding of the mechanisms underlying the pathogenesis of anti-NMDAR encephalitis. The autoantibodies bind to and cross-link the endogenous NMDARs, disrupt the interaction of NMDARs with receptor tyrosine kinase EphB2 leading to internalization and reduced function of NMDARs. Hypofunction of the NMDARs results in impairment in long-term potentiation and deficit in learning and memory, leads to development of depression-like behavior, and lowers the threshold for seizures. Recent development of active immunization models of anti-NMDAR encephalitis provides insight into the inflammation process and paves the way for further studies that may lead to better treatment.

Keratins play multiple significant biological roles in epithelium. Keratin 1 (K1)/keratin 10 (K10) heterodimer is a hallmark for keratinocyte differentiation. While keratins are absent in normal melanocyte, keratins have been found in both melanoma cell lines and human melanoma. The biological significance of the keratins in melanoma cells has remained unclear. In our current study we applied K1 siRNA to investigate the biological significance of K1 in B16-F10 melanoma cells. We found that as low as a 16% decrease in the K1 level led to significant increases in both apoptosis and necrosis of the cells. Moreover, the mild K1 decrease led to significant increases in both dichlorofluorescein (DCF) and ethidium signals - two indicators of oxidative stress - in the cells. Collectively, our findings have provided the first evidence indicating both a critical role of the K1 in maintaining the survival of melanoma cells and an important role of the K1 in modulating the oxidative stress state of the cells. These findings have exposed new functions of keratins in cancer cells, suggesting that K1 may become a novel therapeutic target for melanoma.

The growing need for personalized medicine for cancer patients has enhanced and optimized the production of living tumor organoids that have become optimal preclinical models for the discovery and screening of anticancer drugs. The systematic collection and storage of tumor organoids through the establishment of dedicated biobanks will represent a fundamental tool for cancer research and clinical trials.

Electrical synapses formed by gap junctions occur at a variety of neuronal subcellular sites in the mammalian central nervous system (CNS), including at somatic, dendritic and axon terminal compartments. Numerous electrophysiological studies using mice and rats, as well as computer modelling approaches, have predicted the additional occurrence of electrical synapses between axons near their emergence from neuronal somata. Here, we used immunofluorescence methods to search for localization of the neuronal gap junction-forming protein connexin36 (Cx36) along axon initial segments (AISs) labelled for the AIS marker ankyrinG. Immunofluorescent Cx36-puncta were found to be associated with AISs in several CNS regions of mice, including the spinal cord, inferior olive and cerebral cortex. Localization of Cx36-puncta at AISs was confirmed by confocal single scan and 3D imaging, immunofluorescence intensity profiling and high resolution structured illumination microscopy (SIM). AISs measuring up to 30 µm in length displayed typically a single Cx36-punctum and the incidence of these long AISs displaying Cx36-puncta ranged from 3% to 7% in the inferior olive and in various layers of the cerebral cortex. In the inferior olive, the gap junction associated protein zonula occludens-1 (ZO-1) was found to be co-localized with Cx36-puncta on AISs, indicating that these puncta have some of the molecular constituents of gap junctions. Our results add to the neuronal subcellular locations at which Cx36 is deployed, and raise possibilities for its involvement in novel functions in the AIS compartment.

Background: Circadian rhythm is intracellular molecular mechanisms, influenced by environmental factors such as light, noise, mealtime, and sleep pattern. Shift work affects the sleep pattern, mealtime and psychological aspects of workers. This study aims to compare the effect of shift work on circadian dysynchrony among nurses in two different groups based on the duration of shift work.

Material and method: It was a cross-sectional, preliminary study done at a tertiary care teaching hospital in North India. The study enrolled 170 nurses (aged <35 years) performing shift duties for last 3 years (group-1) and 1 year (group-2) respectively in a 1:1 ratio. Tools used to collect data were case reporting form (demographic and clinical variables, anthropometric measures), Hamilton Anxiety Rating Scale, and Pittsburg Sleep Quality Index.

Results: Mean age of participants was 27.39±2.89 vs. 26.14±2.45 in group 1 and 2. We found significant positive correlation of duration of shift work with diastolic blood pressure (DBP) (P=0.000), systolic blood pressure (SBP) (P=0.001), body fat % (P=0.019), weight (P=0.034), hip circumference (HC) (P=0.000) and also significant difference between means of DBP (P=0.001) and HC (P=0.003) in both groups. Whereas bad sleep quality was found in 79% and 66% of participants in group 1 and 2 respectively, the prevalence of moderate to severe anxiety in groups 1 and 2 was 60% and 37% respectively.

Conclusion: Long duration of shift work increases the risk of developing cardiometabolic risk factors as a consequence of circadian dysynchrony and varies with the duration of shift work.

Background: Anterior cruciate ligament (ACL) rupture is an important disease in the younger population and especially professional athletes followed by trauma. There are different surgical methods for repairing ACL rupture each having their own prognosis rates. Here in this study, we investigated and compared results of ACL reconstruction after the fixed loop and adjustable loop surgical procedure in patients with ACL rupture.

Methods: In this study, we evaluated 60 patients with ACL rupture and divided them into two groups each containing 30 patients. Fixed loop and adjustable loop ACL repair were performed for each group. Data regarding knee society score, static laxity, and joint range of motion (ROM), patient's satisfaction and returning to normal daily activities were collected and compared between two groups after 6 months follow up using SPSS software.

Results: We showed that there was no significant difference between two groups of patients regarding investigated factors (P>0.05). No surgical site infections were also observed during the study.

Conclusion: Both fixed loop and adjustable loop grafting procedures for ACL repair indicate beneficial results and are effective in patients with ACL rupture. We suggest that orthopedic surgeons could use each of these methods according to their own experience and the patient's condition. There are no significant differences between these two methods in the prognosis of patients.

Many physiological and behavioral changes take place during pregnancy to ensure the growth and development of a healthy fetus. This study investigates the effects of high maternal salt intake during pregnancy on lipid parameters in Wistar rats. Twenty female Wistar albino rats (200-250 g) were used for the study. The rats were time-mated and day 1 of pregnancy was determined by the presence of spermatozoa after a vaginal lavage. Animals were then randomly divided into two groups: a standard control diet and high-salt diet (8% NaCl) of 10 rats each. On the 19^th day, the animals were fasted overnight and sacrificed under anaesthesia. Blood samples were collected via cardiac puncture for determination of lipid parameters triglyceride (TG), total cholesterol (TC), high density lipoprotein-cholesterol (HDL-c), low density lipoprotein-cholesterol (LDL-c), and very low density lipoprotein-cholesterol (VLDL-c) using enzymatic colorimetric method. Atherogenic indices, triglyceride/HDL-C (TG/HDL-C) and total cholesterol/HDL-C (TC/HDL-C) ratios were calculated. SPSS 21.0 package was used for data analysis and level of significance was analyzed using student t-test. Significance was set at P<0.05. Result showed significant (P<0.05) increases in plasma level of TG, TC, LDL-C VLDL-C, TG/HDL-C and TC/HDL-C ratios in high salt fed pregnant rats compared to control. No significant (P>0.05) change was observed in HDL-C level in high salt fed pregnant rats when compared with control. High salt intake during pregnancy has detrimental effect on maternal lipid profile which can threaten both maternal and the fetal life.