Sami Aydogan

Melatonin and nitric oxide

Melatonin is a product of the amino acid tryptophan in the pineal gland. Once synthesized, the specific mechanisms governing the release of melatonin from the pineal gland and its functions are largely unknown. Besides its regulatory role in circadian rhythms in mammals, because of its widespread subcellular distribution, melatonin contributes to the reduction of oxidative damage in both the lipid and the aqueous environments of the cell. This postulate is widely supported by the experimental observations showing that melatonin protects lipids in membranes, proteins in the cytosol, and DNA in the nucleus and mitochondria from free radical damage. Melatonin thus reduces the severity of disease conditions where free radicals are implicated. The direct free radical scavenging effects of melatonin are receptor independent. It has recently been shown that it has an ability to scavenge free radicals, including hydroxyl radicals, hydrogen peroxide, peroxyl radicals, singlet oxygen and nitric oxide (NO) and peroxynitrite anion. An excessive amount of NO, a free radical which is generated by the inducible form of NO synthase, is known to cause cytotoxic changes in cells. Hence, NO synthase is considered a pro-oxidative enzyme, and any factor that reduces its activity would be considered an antioxidant. Recent studies have shown that melatonin inhibits the activity of NO synthase, beside its NO and peroxynitrite scavenging activity. Thus, inhibition of NO production may be another means whereby melatonin reduces oxidative damage under conditions, such as ischemia-reperfusion, sepsis, etc, where NO seems to be important in terms of the resulting damage. (J. Endocrinol. Invest. 28: 281–287, 2005)

Impaired erythrocytes deformability in H(2)O(2)-induced oxidative stress: protective effect of L-carnosine.

Impaired red blood cell deformability is a hemorheological perturbation induced by many kinds of diseases. An increase in free radicals causes a reduction in erythrocyte flexibility and deformability. Carnosine is a dipeptide abundant in skeletal muscle and brain of humans. One of the main function of carnosine is its antioxidant and free-radical scavenger effect. In this study our aim is to investigate the protective effect of L-carnosine on RBCs in H(2)O(2)-induced oxidative stress in vitro conditions. Twenty male wistar albino rats, 10 were 3 months old, 10 were 12 months old used. The blood from each rat were divided into ten tubes and these blood samples divided into two groups. The first tube of the first group was the control and the rest 4 tubes were treated with different concentrations of L-carnosine. All tubes in the second group were incubated with H(2)O(2) additively. The deformability indexes of the erythrocytes were measured by a laser diffractometer (Myrenne Rheodyne SSD).L-carnosine has improved the RBC deformability significantly which is impaired by H(2)O(2) treatment (p<0.05). Increase in deformability is more significant in young rat group when compared to old rat group.L-carnosine, as an antioxidant molecules, has a dose dependent positive effect on RBC deformability and has improved or protect the deformability of erythrocytes, especially in young rat group which impaired by H(2)O(2)-induced oxidative stress in vitro conditions. The results of this study first suggest that L-carnosine supplemention can be used to improve the RBC quality or to protect them from oxidative damage in survival of RBC in the circulation.

Biological understanding of the cardiovascular risk associated with major depression and panic disorder is important.

Abstract Introduction. Panic disorder (PD) and major depressive disorders (MDD) are serious mental disorders but the mechanisms underlying the pathophysiology are poorly understood. Nitric oxide (NO) is a gas considered to play an important role in mediating anxiety and stress response and is synthesised from nitric oxide synthase (NOS). The endothelial isoform (eNOS) has been found also in platelets. Homocysteine (Hcy) is an amino acid which naturally occurs in the human body. Elevated levels are linked to increased risk of cardiovascular, neurological and psychiatric diseases. In this study we aimed to evaluate NO, platelet aggregation and Hcy levels in PD and MDD patients. Materials and methods. Nineteen PD and 18 MDD patients participated in this study. NO levels were measured spectrophotometrically, platelet aggregation levels were measured in an aggregometer and Hcy levels were measured by HPLC. Results. NO levels were significantly lower in patients with MDD and PD than in control subjects (P < 0.05). Hcy and platelet aggregation levels were significantly higher in patients with MDD and PD than in control subjects (P < 0.05). Conclusion. Further more detailed studies are needed to find out the effects of drugs on these parameters or to disclose the exact mechanism underlying the alteration of these parameters.

Effect of carnosine on erythrocyte deformability in diabetic rats

It is known that oxidative stress plays an important role in the chronic complications of diabetes. Lipid peroxidation is one of the consequences of oxidative stress. Erythrocyte deformability abilities are reduced as a result of lipid peroxidation. Conversely, a decrease nitric oxide (NO) production seems to be responsible in endothelial dysfunction which occurs in diabetic vascular complications. Carnosine is a molecule with anti-oxidant properties. The aim of this study was to investigate erythrocyte deformability indices and the effects of carnosine on erythrocyte deformability in diabetes and to determine a possible relationship between carnosine and nitric oxide. Male Wistar albino rats were used in the study. Injections were administered to seven groups consisting of eight rats each. The groups were: Control, Carnosine, L-NAME (NG-nitro-L-arginine methyl ester), Diabetic, STZ (Streptozotocin) +Carnosine, STZ+L-NAME and STZ+Carnosine+L-NAME. In addition, glucose, insulin, MDA (Malondialdehyde) and NO levels were measured and erythrocyte deformability indices were calculated in all groups. Erythrocyte deformability indices and NO levels were decreased and MDA levels were found to be increased in diabetic group. It was also found that carnosine can significantly reverse erythrocyte deformability, reduce lipid peroxidation and increase NO levels in diabetes. It can be concluded that carnosine can recover from microvascular circulation problems by increasing erythrocyte deformability, can protect cells and tissues against lipid peroxidation and can be used as a multi-functional anti-oxidant in the treatment of diabetes mellitus to prevent the complications of diabetes.

Electrophysiological evidence of biphasic action of carnosine on long-term potentiation in urethane-anesthetized rats

Carnosine is a dipeptide synthesized by the carnosine synthetase from β-alanine and l-histidine. The well-known effects of carnosine may be related with mechanisms producing long-term potentiation which is one of the electrophysiological signs of memory. In the present study we aimed to investigate the effect of four different doses of carnosine on long-term potentiation in urethane-anesthetized rat. A bipolar stimulating electrode was placed in the medial perforant path and a double-barrel glass micropipette was placed in the dentate gyrus as the recording electrode. Artificial cerebrospinal fluid (in the control group) or carnosine (0.1, 1, 10, and 100μg/μL) was infused into the dentate gyrus. Our results showed that the I/O curve of the excitatory postsynaptic potential slope or population spike amplitude was not significantly shifted by carnosine. We found that population spike amplitude increased to 244% and 287% at the dose of 100μg/μL in the post-tetanic and induction phases, respectively, but decreased to 163% and 186% at the dose of 0.1μg/μL and to 145% and 162% at the dose of 1μg/μL when compared with 203% and 232% of the control values. However, there were no significant differences for the slope of excitatory postsynaptic potential. Carnosine had no effect on the EPSP slope or PS amplitude recorded from the dentate gyrus in response to test stimuli when high-frequency stimulation was not delivered. In the present study, we speculated that the effects of carnosine in lower or higher doses could be explained by its effect on different processes, such as soluble guanylyl cyclase inhibition or the conversion of carnosine into histamine.

The effects of colorectally insufflated oxygen-ozone on red blood cell rheology in rabbits

Currently, with reappraisal of ozone therapy, it has been utilized worldwide in research and clinical field. Most of the studies investigating effects of ozone on blood parameters are conducted by directly ozonating the blood. Rectal insufflation is a simple, easy and inexpensive method of delivering ozone. Little is known how these gases affect some fundamental hemorheologic parameters when given by insufflation. We aimed to investigate the effects of colorectally insufflated oxygen-ozone on red blood cell rheology in rabbits. Rabbits were divided into Group 1 (control); Groups 2, 3 and 4 (oxygen rectally insufflated respectively for 15, 21 and 36 days); Groups 5, 6 and 7 (ozone rectally insufflated respectively for 15, 21 and 36 days). Erythrocyte deformability, aggregation and osmotic fragility were determined from blood samples at the end of each treatment period. Our study showed an improvement in deformability, a decrease in aggregation and an increase in fragility following a 15 day ozone treatment. With longer ozone application the changes in aggregation and fragility returned back to control levels, however its effect on deformability sustained. Therefore, more than two weeks ozone insufflation may induce adaptation to changes induced by ozone suggesting its systemic effects.

Gender-related alerations in erythrocyte mechanical activities under desflurane or sevoflurane anesthesia

Alterations in erythrocyte mechanical activities under the influence of anesthesia have been observed and discussed among the responsible factors for the deterioration of tissue and organ perfusion related to anesthetic procedures.21 female and 17 male Swiss Albino rats were used. Female (f) and male (m) rats were divided into 3 groups; control (f (n=7); m (n=5)), sevoflurane treated group (f (n=7); m (n=5)), desflurane treated group (f (n=7); m (n=7)). 2% of sevoflurane or 6% desflurane were applied to the rats with inhalation in an adjustable cage for one hour. The deformability indexes of the erythrocytes were measured by a laser diffractometer (Myrenne Rheodyne SSD). Sevoflurane anesthesia has improved the deformability of erythrocytes in male rats (p<0.05) whereas there were not any significant changes in female rats. Desflurane has improved the deformability of erythrocytes in both gender significantly (p<0.05). Volatil anesthetic agents sevofluran and desflurane has improved the mechanical properties of the erythrocytes in male rats compared to their controls. However, these changes were not significant with sevoflurane in females. The results in male rats may be due to the effects of testosterone on the flexibility of the erythrocytes leading them to tolerate to the environmental changes. These results reveal that the inhalation anesthetics like sevoflurane and desflurane are appropriate anesthetics which can improve the deformability of erythrocytes during surgery.

Changes of red blood cell rheology in newborns with congenital hypothyroidism during treatment.

Abstract Aim: We aimed to evaluate the deformability characteristics of RBC and the affecting factors in newborns diagnosed with congenital hypothyroidism (CH) and to compare the outcomes after the l-thyroxin treatment. Patients and methods: Enrolled subjects were divided into two subgroups as “patients” and age-matched healthy “controls”. First blood samples were taken from all subjects for measuring elongation index (rEI) and osmotic fragility of RBC (OF), hematic and biochemical analytes affecting the RBC deformability in the neonatal age. All parameters were repeated a month after provided euthyroid state following the treatment in patients and age-matched healthy controls. Results: There was no difference between both groups in terms of complete blood count parameters and serum analytes (albumin, bilirubin and fibrinogen) except expected age-related changes in the first and second readings. Serum lipid/lipoprotein levels of both groups remained unchanged except triglyceride levels during the study period. The rEI of the patients were lower than that of controls in the first and second readings. The rEIs of the patients became increased, reaching (not equal) the levels of their controls during l-thyroxin treatment. Osmotic fragility of the patients was detected as lower than controls in the first and second readings, and became better during l-thyroxin treatment. Conclusion: Our results indicate that some changes may occur on the hematic and biochemical analytes affecting the RBC deformability features. Neonates with CH have the worst rEI initially, but they reached the indices of the healthy infants thanks to l-thyroxin treatment. Also, their OF features have been improved by l-thyroxin.

The effects of 20-m repeated sprint training on aerobic capacity in college volleyball players

Summary Study aim: The purpose of this study was to examine the effects of a repeated sprint training program in addition to volleyball training on the aerobic capacity of college volleyball players. Materials and methods: Eighteen male volleyball players were randomly assigned to either an experimental group (n = 9, age: 21.2 ± 1.3 years) or a control (n = 9, age: 21.2 ± 1.6 years) group. Both groups followed a traditional volleyball training program three times per week for 6 weeks. The experimental group additionally performed a repeated sprint training protocol immediately before each volleyball training session. The repeated sprint training consisted of 1-3 sets of 5 × 20 m maximal sprints with 20 seconds of active recovery between sprints and 4 min of passive recovery between sets. Before and after the 6-week training period, all participants performed an incremental treadmill test to determine maximal oxygen uptake (VO2max) and time to exhaustion, and the repeated sprint test (10 × 20 m with a 20‑second recovery between each sprint). Results: The experimental group showed significant improvements in VO2max (+7.1 ± 4.8%; p = 0.001) and running time to exhaustion (+15.8 ± 6.8%; p = 0.004) after training. The best 20-m sprint time (−2.3 ± 2.5%; p = 0.029), mean sprint time (−5.3 ± 3.1%; p = 0.001) and fatigue index (−34.1 ± 28.2%; p = 0.012) also improved significantly in the experimental group. None of these variables changed significantly in the control group (p > 0.05). Conclusions: The current findings indicate that the addition of a repeated sprint training program can improve both the aerobic capacity and anaerobic performance of college volleyball players.

Anesthetics and red blood cell rheology

There are many conditions where it is useful for anesthetists to have a knowledge of blood rheology. Blood rheology plays an important role in numerous clinical situations. Hemorheologic changes may significantly affect the induction and recovery times with anesthetic agents. But also, hemorheologic factors are directly or indirectly affected by many anesthetic agents or their metabolites. In this review, the blood rheology with special emphasis on its application in anesthesiology, the importance hemorheological parameters in anesthesiology and also the effect of some anesthetic substances on red blood cell rheology were presented.