Hulagu Bariskaner

The mechanisms of vasorelaxant effect of leptin on isolated rabbit aorta

In the present study, we analysed the effects of leptin on rabbit aorta and the mechanisms underlying these effects. Leptin (10−12–10−9 m) induced concentration‐dependent relaxation in intact rabbit aorta rings precontracted with phenylephrine (10−6 m). Removal of endothelium abolished the effects of leptin. Pretreatment of rings with Nω‐nitro‐l‐arginine methyl ester (10−4 m 20 min) or catalase (1200 U/mL 20 min) significantly reduced the relaxant response to leptin when compared with the control group. The incubation of brefeldin A (3.5 × 10−5 m 90 min), indomethacin (10−5 m 20 min), tetraethylammonium (10−4 m 20 min), and glibenclamide (10−5 m, 20 min) did not affect the leptin‐induced vasodilation. These results suggest that leptin relaxes the rabbit aorta. The relaxation is mediated by endothelium‐derived nitric oxide and hydrogen peroxide.

Effect of gabapentin on postoperative pain: A randomized, placebo-controlled clinical study

Background: Both clinical and experimental studies suggest that gabapentin (GBP) has analgesic effects in neuropathic pain. The aim of the study was to investigate the effect of gabapentin on postoperative pain. Methods: This study was performed on 45 (ASA I-II) patients planned for major orthopaedic surgery. 45 patients were randomized into three equal groups. Patients received 1200 mg GBP (Group I), 800 mg GBP (Group II) or placebo (Group III) 1 h before surgery. Anaesthesia was standardized for all patients. Morphine by intravenous patient-controlled analgesia was applied as 1 mg bolus dose and 7 min lockout time for postoperative analgesia. The pain was evaluated at the first 2 and 4 h after operation. The amount of morphine used was recorded at the same hours. Results: In all groups, there were no significant differences in the demographic characteristics, duration of surgery and anaesthesia, or dose of fentanyl received in the operating room. Pain scores and side effects were similar in all groups. Morphine consumption was lower in the Groups I and II than in the Group III at 2 h and 4 h postoperatively ( p< 0.05). Morphine consumption was lower in the Group I than in the Group II at 2 h and 4 h ( p< 0.05). Conclusion: Our results demonstrate that a single dose of 1200 or 800 mg oral gabapentin reduces morphine consumption in the early postoperative period. However, gabapentin 1200 mg is more effective than gabapentin 800 mg for pre-emptive analgesic effect. summary

Selenium-Induced Changes on Rat Sciatic Nerve Fibers : Compound Action Potentials

The nervous system, through its important role as a communication network, governs reactions to stimuli, processes information and generates elaborate patterns of signals to control complex behaviors. Although selenium (Se) was shown to have some beneficial effects in pathological conditions, it is still a toxic element with a fairly small therapeutic window. In this study, the direct effects of Se ranging from 10(-8) to 10(-4) M were tested on rat sciatic nerve preparations. The toxicity started at 10(-8) M and the degree of alterations was found to be dose-dependent. In between the measured parameters, total compound action potential area (Astart = 3.70 +/- 0.16 ms x mV and A(-8) M = 3.04 +/- 0.14 ms x mV) and maximum depolarization points (MDstart = 6.70 +/- 0.22 mV and MD(-8) M = 6.04 +/- 0.18 mV) were the first to be affected from 10(-8) M. Latencies and conduction velocity distribution measurements have shown that nerve fibers having intermediate conduction velocities (20-35 m/s) are the first to be affected from this toxicity. Despite the fact that the new claims concluded the positive effects of the administrations, it is evident that the dose of supplementation must be fine-tuned to avoid possible side effects.

THE EFFECT OF BUPIVACAINE ON COMPOUND ACTION POTENTIAL PARAMETERS OF SCIATIC NERVE FIBERS

The aim of this study was to document the effects of the local anesthetic agent bupivacaine on individual fibers of peripheral nerve. To accomplish this objective, compound action potentials (CAPs) were recorded from isolated frog sciatic nerves treated with bupivacaine for seven individual concentration levels. Numerical and fast Fourier transform (FFT) analysis were performed on these recordings. The areas, latency periods, maximum and minimum derivatives, and power spectrums of the CAPs were computed. The results show that the area and the absolute values of maximum and minimum derivatives decrease linearly as bupivacaine concentration increases. The power spectrum of the CAPs, which resides in the 0-1000 Hz interval, initially shifts to higher frequencies then returns to lower frequency region again with increasing bupivacaine concentration. Due to this result, it is thought that bupivacaine inhibits nerve fibers in a dose-dependent manner. It primarily affects the fibers having the least myelin sheets (motor fibers), then it begins to depress the fast conducting (neurosensorial) fibers as the bupivacaine concentration increases, and finally blocks the unmyelinated C-fibers

Celecoxib administration reduced mortality, mesenteric hypoperfusion, aortic dysfunction and multiple organ injury in septic rats.

BACKGROUND The cyclooxygenase (COX)-2 overexpression is associated with vascular injury and multiple organ failure in sepsis. However, constitutive COX-1 and basal COX-2 expressions have physiological effects. We aimed to investigate the effects of partial and selective COX-2 inhibition without affecting constitutive COX-1 and basal COX-2 activities by celecoxib on mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries, and survival in septic rats accomplished by cecal ligation and puncture (CLP). METHODS Wistar rats were allocated into Sham, CLP, Sham+celecoxib, CLP+celecoxib subgroups. 2h after Sham and CLP operations, celecoxib (0.5mg/kg) or vehicle (saline; 1mL/kg) was administered orally to rats. 18h after drug administrations, MABF and responses of isolated aortic rings to phenylephrine were measured. Tissue samples were obtained for biochemical and histopathological examinations. Furthermore, survival rate was monitored throughout 96h. RESULTS Celecoxib ameliorated mesenteric hypoperfusion and partially improved aortic dysfunction induced by CLP. Survival rate was%0 at 49th h in CLP group, but in CLP+celecoxib group it was 42.8% at the end of 96h. Serum AST, ALT, LDH, BUN, Cr and inflammatory cytokine (tumor necrosis factor-alpha, interleukin-1 beta and interleukin-6) levels were increased in CLP group that were prevented by celecoxib. The decreases in liver and spleen glutathione levels and the increases in liver, lung, spleen and kidney malondialdehyde levels in CLP group were blocked by celecoxib. The histopathological protective effects of celecoxib on organ injury due to CLP were also observed. CONCLUSIONS Celecoxib has protective effects on sepsis due to its preservative effects on mesenteric perfusion, aortic function and its anti-inflammatory and antioxidative effects.

Effects of simvastatin on bleomycin-induced pulmonary fibrosis in female rats

Statins reduce cholesterol levels by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A reductase and have a major place in the treatment of atherosclerotic disease. Recent studies have shown anti-inflammatory properties of statins. The purpose of this study was to evaluate the anti-inflammatory effect of simvastatin on bleomycin (BLM)-induced pulmonary fibrosis in rats. A total of 31 female Sprague-Dawley rats were divided into four groups: (1) intratracheal (IT) phosphate-buffered saline (PBS) + intraperitoneal (IP) PBS (n=7); (2) IT BLM + IP PBS (n=8); (3) IT BLM + low dose (LD) simvastatin (1 mg/kg daily, n=8); (4) IT BLM + high dose (HD) simvastatin (5 mg/kg daily, n=8). Simvastatin was administered IP for 15 days, beginning 1 day prior to IT BLM. The effect of simvastatin on pulmonary fibrosis was studied by measurements of IL-13, PDGF, IFN-γ, TGF-p1 levels in bronchoalveolar lavage (BAL) fluid and lung tissue hydroxyproline (HPL) content and by histopathological examination (Ashcroft score). BLM caused significant change in BAL fluid cytokine levels and increased both HPL content and histopathological score (p<0.001 for all). While LD simvastatin had no effect on cytokine levels, HD significantly reduced IL-13 (15.12 ±7.08 pg/ml vs. 4.43±2.34 pg/mL; p<0.05) and TGF-β1 levels (269.25 ±65.42 pg/mL vs. 131.75±32.65 pg/mL; p<0.05). Neither HD nor LD simvastatin attenuated HPL content or Ashcroft score. In conclusion, this study showed that LD simvastatin had no effect on a BLM-induced pulmonary fibrosis model, while the high dose caused partial improvement in profibrotic cytokine levels.

Gender-dependent effects of selenite on the perfused rat heart: a toxicological study.

Gender differences are related to the manner in which the heart responds to chronic and acute stress conditions of physiological and pathological nature. Depending on dose, sodium selenite acts as an antioxidant proven to have beneficial effects in several pathological conditions G. Drasch, J. Schopfer, and G. N. Schrauzer, Selenium/cadmium ratios in human prostates: indicators of prostate cancer risk of smokers and non-smokers, and relevance to the cancer protective effects of selenium,Biol. Trace Element Res.103(2), 103–107 (2005); R. G. Kasseroller and G. N. Schrauzer, Treatment of secondary lymphedema of the arm with physical decongestive therapy and sodium selenite: a review,Am. J. Ther.7(4), 273–279 (2000); G. N. Schrauzer, Anticarcinogenic effects of selenium,Cell. Mol. Life Sci.57(13–14), 1864–1873 (2000); I. S. Palmer and O. E. Olson, Relative toxicities of selenite and selenate in the drinking water of rats,J. Nutr.104(3), 306–314 (1974). To date, little is known about the gender-dependent direct effects of toxic doses of selenite on electrophysiology of the cardiovascular system H. A. Schroeder and M. Mitchener, Selenium and tellurium in rats: effect on growth, survival and tumors,J. Nutr.101(11), 1531–1540 (1971); G. N. Schrauzer, The nutritional significance, metabolism and toxicology of selenomethionine,Adv. Food Nutr. Res.47, 73–112 (2003). In the present study, the effects of in vitro toxic concentrations of sodium selenite ranging from 10-6 M to 10-3 M were tested on both male and female rat heart preparations. The toxic effects seen in an electrocardiogram and left ventricular pressure were dose and sex dependent at most of the tested concentrations. The present study clearly shows that at toxic doses, stress conditions are induced by selenite, resulting in gender-dependent modifications of the heart function. This modification is more pronounced in the contraction cascade of female rats. Males, on the other hand, had been much more affected in excitation-related parameters.

Thymoquinone protects against the sepsis induced mortality, mesenteric hypoperfusion, aortic dysfunction and multiple organ damage in rats

BACKGROUND Thymoquinone (TQ) is a potent cytoprotective, antioxidant and anti-inflammatory agent. We aimed to investigate the possible protective effects of TQ on survival, mesenteric artery blood flow (MABF), vascular reactivity, oxidative and inflammatory injuries in a murine sepsis model induced by cecal ligation and puncture (CLP). METHODS Wistar rats were divided into the following four groups: Sham, CLP, Sham+TQ and CLP+TQ. TQ (1mg/kg/day) or vehicle (dimethyl sulfoxide, 1mL/kg/day) was intraperitoneally injected for 3 days. At 4th day Sham or CLP operation was applied. 20h after the operations, MABF and contractile responses of isolated aortic rings to phenylephrine were measured. Tissue samples were obtained for histopathological and biochemical examinations. Also, survival rates were recorded throughout 96h. RESULTS TQ ameliorated mesenteric hypoperfusion and partially attenuated aortic dysfunction induced by CLP. Survival rate was %0 at 42nd h in CLP group, but in CLP+TQ group it was 33.4% at the end of 96h. Serum levels of AST, ALT, LDH, BUN, Cr and inflammatory cytokines (tumor necrosis factor-α, interleukin-1 β and interleukin-6) increased in CLP group that were prevented by TQ. The decreases in liver, spleen and kidney glutathione levels and the increases in liver, lung, kidney and spleen malondialdehyde levels induced by CLP were inhibited by TQ. The histopathological protective effects of TQ on multiple organ damage due to CLP were also observed. CONCLUSION TQ has ameliorative effects on sepsis due to its protective effects on mesenteric perfusion, contractile function of aorta and its anti-inflammatory and antioxidative effects.

Infliximab alleviates the mortality, mesenteric hypoperfusion, aortic dysfunction, and multiple organ damage in septic rats

Tumor necrosis factor-alpha (TNF-α) is a pivotal mediator that triggers inflammatory process, oxidative stress, and multiple organ injury in sepsis. We investigated the effects of infliximab on survival, mesenteric artery blood flow (MBF), vascular reactivity, and oxidative and inflammatory injuries in cecal ligation and puncture (CLP)-induced sepsis. Wistar rats were divided into Sham, CLP, Sham+infliximab, and CLP+infliximab subgroups. Twenty-four hours before the operations, rats were injected intraperitoneally with infliximab (7 mg/kg) or vehicle (saline; 1 mL/kg). Twenty hours after the operations, MBF and phenylephrine responses of isolated aortic rings were measured. Tissue damages were examined biochemically and histopathologically. Furthermore, survival rates were monitored throughout 96 h. Infliximab improved survival, mesenteric perfusion, and aortic function after CLP. Increases of serum AST, ALT, LDH, BUN, Cr, and inflammatory cytokines (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6) induced by CLP were blocked by infliximab. Infliximab prevented malondialdehyde elevations in septic liver, lung, spleen, and kidney tissues, as well as glutathione reductions in septic liver, spleen, and kidney tissues. Protective effects of infliximab on multiple organ damage were also observed histopathologically. Infliximab showed protective effects in sepsis due to its improvement effects on mesenteric perfusion, aortic function, and its anti-inflammatory and antioxidative effects.

Systemic effects of epidural betamethasone injection

AbstractA single epidural injection of a steroid may produce a suppression of the adrenocortical secretion. We aimed to evaluate systemic effects of a single epidural injection of betamethasone in this study. The study included 33 patients with low back pain. None of the patients had received local or systemic steroid therapy within 2 months before the injection. The epidural injection consisted of 10 mg of betamethasone diluted in 8 ml 0.25% bupivacaine. Injections were performed between 8:00 and 9:00 a. m. Before the injection in the same day (D0) cortisol, ACTH, fasting levels of glucose, triglycerides, cholesterol, sodium, and potassium were checked in the blood. The same assays were done again by the same laboratory at 15, 30, 45 min, and 7 (D7) and 21 (D21) days after the steroid injections. In all patients, cortisol and ACTH were normal at D0. ACTH and cortisol significantly decreased 45 min and at D7 after steroid injection, but returned to normal on D21. There were no significant changes in mean ...