Chronic emotional stress exposure increases infarct size in rats: the role of oxidative and nitrosative damage in response to sympathetic hyperactivity.

We investigated the level of sympathetic hyperactivity in response to stress exposure in an acute myocardial infarction (AMI) model and the contribution of oxidative and nitrosative damage to this phenomenon. Stress was induced by 20-day administration of different emotional stress factors: daylight/darkness exposure, overcrowding, isolation, new hierarchy, tilting the cage and restriction of water or food. AMI was induced surgically. Heart rate (HR) and heart rate variability (HRV) measurements were done before and after AMI. Oxidant parameters were measured in heart tissue and cortisol levels were measured in plasma specimens. Compared with the nonstressed group, stress-exposed rats showed sympathetic hyperactivity characterized by increased HR together with decreased HRV. In the stressed group serum corticosterone levels were high both before and after AMI. Mean infarct size in the stressed group was significantly larger (44.6+/-3.23% and 53.1+/-4.52%, respectively; P<0.05). Increased tissue malondialdehyde (MDA) levels (0.63+/-0.59 and 1.60+/-0.31 nmol/mg protein, respectively; P<0.05) and decreased superoxide dismutase (SOD) activity and glutathione (GSH) content were seen in stress-exposed rats. Likewise, heart peroxynitrite levels were also high in stress-exposed rats (141.8+/-18 nmol/g tissue vs. 164.2+/-21 nmol/g tissue). Chronic emotional stress is a deteriorating factor for the induction and prognosis of MI. Exaggerated sympathetic activity may be the major contributing factor. Oxidative and nitrosative damage in response to this sympathetic hyperactivity is the key mechanism.

Antidepressant-like effect of hyperbaric oxygen treatment in forced-swimming test in rats.

The present study was undertaken to assess the antidepressant-like activity of hyperbaric oxygen (HBO) treatment and also to investigate whether in the forced-swimming test HBO treatment interacts with the antidepressant effects of fluoxetine, a selective serotonin reuptake inhibitor, and imipramine, which is mainly a noradrenaline reuptake inhibitor. HBO treatment (at 2.4 atmospheres absolute [ATA] for 60 min) significantly reduced the immobility time in this test; in other words, it displayed antidepressant-like activity. The coadministration of HBO with fluoxetine (5 mg/kg) or imipramine (5 mg/kg) at their ineffective doses produced greater inhibition of immobility time compared with HBO alone. In conclusion, HBO treatment might be an alternative approach to antidepressant therapy, alone or in combination with antidepressant drugs.

Hyperbaric oxygen treatment reduces carrageenan-induced acute inflammation in rats.

The present study was designed to assess the anti-inflammatory activity of hyperbaric oxygen treatment by comparing it with that of diclofenac, a nonsteroidal anti-inflammatory drug, and also to investigate whether hyperbaric oxygen treatment enhances the anti-inflammatory effect of diclofenac in carrageenan-induced paw edema which is commonly employed as an acute inflammation model in rats. Hyperbaric oxygen treatment and diclofenac (20 mg/kg) markedly reduced the carrageenan-induced paw edema in rats. In other words, they displayed anti-inflammatory activity. On the other hand, hyperbaric oxygen treatment did not consistently modify the anti-inflammatory effect of diclofenac in this model.

The extended V-Y flap for coverage of a mid-planatar defect.

A mid-plantar ulcer was successfully reconstructed with an extended V-Y flap incorporating part of the flexor digitorum brevis muscle to achieve more volume and increase the safety of the flap. This flap can be used as a reliable alternative to other techniques to repair a moderately sized defect of the plantar midfoot.

Therapeutic drug monitoring in Turkey: experiences from Istanbul.

Therapeutic drug monitoring (TDM) has assumed an important place in patient management in the last few decades. In this study, serum drug levels determined in 7759 specimens sent to the Department of Pharmacology and Clinical Pharmacology in 1994 and 1998 for TDM were retrospectively evaluated. Monitored drugs were carbamazepine, valproate, phenytoin, phenobarbital, digoxin, theophylline, and salicylate. The comparison of the results obtained for the relevant 2 years showed that there was a remarkable increase in the number of requests for TDM per year and in the rate of serum drug levels that were within therapeutic range. Serum antiepileptic drug level monitoring accounted for a major part of the data. Overall data suggest that the use of TDM in antiepileptic drugs is improving; conversely, digoxin and theophylline are still not being properly monitored. In this study, the results are discussed in the light of rational TDM criteria.

Antinociceptive effect of amikacin and its interaction with morphine and naloxone.

Amikacin sulphate (30 mg kg(-1)) administered either intraperitoneally (i.p.) or subcutaneously (s.c.) produced antinociceptive effect in BALB/c mice in the acetic acid writhing test which is employed as an inflammatory pain model. The lack of difference between two routes with regard to antinociceptive potency was taken as evidence for the absence of a local effect. Amikacin sulphate-induced antinociception seems unlikely to be due to non-specific behaviour alteration, since this drug, at a dose range of 15-100 mg kg(-1)did not affect motor coordination of mice in rot-a-rod test. Morphine (1 mg kg(-1)) also caused antinociception when administered i.p. or s.c. but the effect was greater with the latter route. At the i.p. site; the concurrent use of amikacin and morphine produced more remarkable antinociception compared to their individual usages. Besides, naloxone (2 mg kg(-1)) significantly decreased antinociceptive effect of amikacin but itself also exerted antinociception. At present, we have no plausible explanation for these findings at the i.p. site.