Pinealectomy increases ouabain high-affinity binding sites and dissociation constant in rat cerebral cortex.

The effect of the pineal gland on the ouabain high-affinity binding sites (Kd = 3.1 +/- 0.4 nM, Bmax = 246.4 +/- 18.4 fmol/mg protein) in rat cerebral cortex was studied. Pinealectomy increased Bmax (940.7 +/- 42.8 fmol/mg protein) and Kd (7.6 +/- 1.5 nM) while melatonin injection (100 micrograms/kg b.wt.) counteracted these effects, restoring kinetic parameters (Kd = 1.9 +/- 0.05 nM; Bmax = 262.2 +/- 29.6 fmol/mg prot) to control values. Melatonin activity on ouabain binding in vitro did not depend upon a direct effect on the binding sites themselves. However, in competition experiments, melatonin increased binding affinity of ouabain as shown by the decreased IC50 values.     

Changes in oxygen saturation in the jugular bulb during cardiac surgery

OBJECTIVE: Heart surgery with cardiopulmonary bypass (CPB) leads to changes in supply and consumption of cerebral oxygen (DO2 and VO2C). Monitoring jugular bulb oxygen saturation (SjO2) detects changes in the DO2C/VO2C ratio that occur in patients undergoing heart surgery. The objective of this study was to determine the evolution of SjO2, of the arteriovenous difference of cerebral oxygen and of cerebral oxygen extraction, as well as the possible relation between those variables and changes in mean arterial pressure, hemoglobin counts and temperature in patients undergoing heart surgery with CPB. PATIENTS AND METHOD: A prospective study carried out in 31 patients who underwent coronary valve surgery. To monitor SjO2, each patient's internal jugular vein was cannulated with an oximetric catheter in a retrograde direction to monitor SjO2. RESULTS: Baseline SjO2 (68 +/- 7.4%), obtained after anesthetic induction, was similar to SjO2 before (65 +/- 6%) and after (67 +/- 8.2%) CPB. However, SjO2 upon starting CPB (60 +/- 8.6%) and during rewarming (63 +/- 3%) were significantly lower than at baseline. SjO2 was significantly higher during hypothermic bypass (78 +/- 5%) than at baseline. SjO2 ranged from a low of 60 +/- 8% as CPB was initiated to a high of 78 +/- 5% during hypothermic CPB. Mean arterial pressure was significantly lower at the start of bypass (44 +/- 6 mmHg) than anesthetic induction (83.5 +/- 13.1 mmHg) and the decrease correlated with a significant decrease in SjO2. Changes in mean arterial pressure were unrelated to significant changes in SjO2 at other moments, however. Nor was there a significant relation between changes in temperature or hemoglobin and the evolution of SjO2. At least one episode of SjO2 desaturation (= 50%) occurred in 29% of the patients, with the lowest values being recorded at the start of CPB and during rewarming. CONCLUSIONS: The greatest risk of cerebral oxygen imbalance between supply and demand occurs at the start of CPB and during rewarming, as shown by decreases in SjO2 levels below baseline at those times.     

Cardiovascular Response and Anesthetic Recovery in Electroconvulsive Therapy with Propofol or Thiopental

Propofol provokes a slight hypotensive effect that could mitigate the cardiovascular response to electroconvulsive therapy (ECT). In this study we compared the effects of propofol and thiopental for ECT anesthesia in seven women (22-67 years of age). Anesthesia was induced with either thiopental or propofol, and with atropine and suxamethonium for each treatment. The first anesthesia was assigned to thiopental or propofol at random; the next anesthesia was induced with the other drug, and alternated thereafter. Systolic blood pressure, diastolic blood pressure (DBP), and heart rate (HR) were recorded before anesthesia, after anesthetic induction, and 1 and 5 min after ECT. ECT-induced increases in DBP and HR were less marked with propofol than with thiopental. Seizure durations were decreased with propofol compared with thiopental.     

The effects of ginger supplementation on markers of inflammatory and oxidative stress: A systematic review and meta‐analysis of clinical trials

The present systematic review and meta‐analysis was conducted to investigate the effects of ginger supplementation on markers of inflammatory and oxidative stress. PubMed, Embase, Scopus, and Web of Science were systematically searched to identify relevant clinical trials evaluating the effects of ginger on serum CRP (C‐reactive protein), TNF‐α (tumor necrosis factor‐alpha), IL‐6 (interleukin‐6), PGE2 (prostaglandin E2), TAC (total antioxidant capacity), and MDA (malondialdehyde) from inception up to September 2019. Mean difference and 95% confidence intervals were pooled using a random‐effects model. Potential publication bias was assessed using visual inspection of funnel plot and Egger's weighted regression tests. After excluding irrelevant records, 20 full‐text articles that included 25 separate studies were included to the meta‐analysis. Pooled results of this study indicated a statistically significant effect of ginger on serum CRP, TNF‐α, IL‐6, TAC, and MDA levels following ginger supplementation in compared to the controls. Also, the effects of ginger on serum PGE2 was marginally significant. Moreover, the high heterogeneity was disappeared in subgroup analysis performed by age, duration, dosage, and quality. This current analysis indicates that ginger supplementation has a significant effects on serum inflammatory and oxidative stress markers.     

Toxic effects arising from selenium and deferasirox interaction in the biological system

This investigation was conducted to evaluate the effect of deferasirox on selenium toxicity in male rat organs. After 50 days of selenium administration, all the rats showed toxicity symptoms. After poisoning, deferasirox was given orally to rats during 10 days. The results show that toxicity symptoms were unexpectedly increased. The new symptoms of toxicity after deferasirox administration were including loss of body hairs, yellowish discoloration of hair, weakness, brown spot on their skin, enlargement of the spleen and shrinking of sex organs. Selenium and iron concentrations were determined by GFAAS and FAAS, respectively. The results indicate the poisoned rats with selenium that received deferasirox as a drug, shown serious symptoms such as exacerbate toxicity, reduction in iron concentration, anemia and even death after a few days of deferasirox administration.     

Interleukin-18 Antagonism Improved Histopathological Conditions of Malaria Infection in Mice

Background: Interleukin 18 (IL-18) exerts pleiotropic roles in many inflammatory-related diseases including parasitic infection. Previous studies have demonstrated the promising therapeutic potential of modulating IL-18 bioactivity in various pathological conditions. However, its involvement during malaria infection has yet to be established. In this study, we demonstrated the effect of modulating IL-18 on the histopathological conditions of malaria infected mice. Methods: Plasmodium berghei ANKA infection in male ICR mice was used as a model for malaria infection. Modulation of IL-18 release was carried out by treatment of malarial mice with recombinant mouse IL-18 (rmIL-18) and recombinant mouse IL-18 Fc chimera (rmIL-18Fc) intravenously. Histopathological study and analysis were performed on major organs including brain, liver, spleen, lungs and kidney. Results: Treatment with rmIL-18Fc resulted in significant improvements on the histopathological conditions of the organs in malaria-infected mice. Conclusion: IL-18 is an important mediator of malaria pathogenesis and targeting IL-18 could prove beneficial in malaria-infected host.Key Words: Malaria, Interleukin-18, Plasmodium berghei, Histopathology     

An in vitro study on the effect of vinca alkaloid,vinorelbine, on chromatin histone,HMGB proteins and induction of apoptosis in mice non-adherent bone marrow cells

Context: Vinoreline is a vinca alkaloid anticancer drug widely used in cancer therapy. Drugs are not target specific, therefore might affect normal tissues/cells, in which bone marrow is the important one. Objective: To elucidate the cytotoxic and genotoxic effect of vinca alkaloid anti cancer drug, vinorelbine, on mice non-adherent bone marrow cells in vitro. Materials and methods: Non-adherent bone marrow cells were isolated and exposed to various concentrations (0–160?µg/ml) for 4?h at 23?°C. The chromatin proteins were analyzed by SDS PAGE and western blot. Fluorescent dye staining of the cells, anion superoxide and DNA fragmentations assays were also employed. Result: The results from MTT and trypan blue exclusion assays represented reduction of the cells viability. Extractability of histones and HMG proteins contrasted with difficulty as their content was decreased on SDS-gel upon increasing drug concentration as western blots confirmed it. The amount of degradation form of PARP (89?KD) increased significantly in a dose dependent manner. Increase in anion superoxide production and DNA fragmentation together with cytological detection of chromatin condensation and cellular damage upon exposure of the cells to vinorelbine were indicative of apoptosis induction in these normal cells. Conclusion: Vinorelbine is genotoxic in non-adherent bone marrow cells as affects chromatin components, DNA, histone and HMGB1 proteins and induces apoptosis.