Medical Biochemistry

To investigate the cytokine-stimulating activity of several Mycobacterium phlei cell wall extracts. Th e bacillus Calmette-Guérin application is the gold standard treatment for some types of superfi cial bladder carcinoma. However, its usage is limited due to its harmful side eff ects. Intensive research has been carried out to fi nd less toxic and more potent therapeutic agents for treatment. Researchers focus on M. phlei for this purpose. Th e cell wall extract of M. phlei is suffi cient for antitumoral activity.

S ekonder metabolitler, organizma herhangi bir stres durumuyla karşılaştığı zaman faaliyete geçen özelleşmiş metabolik yollar tarafından üretilirler. Bu ürünlerin ara metabolizma ürünlerinden farkı, organizmanın büyümesi ve üremesi için mutlak gerekli olmamalarıdır. Buna rağmen organizma için önemli birtakım fonksiyonlar üstlenirler. Atıkların uzaklaştırılması, detoksifikasyon, savunma ve hücreler arası haberleşme bu fonksiyonlar arasındadır . Üretildikleri organizma için üstlendikleri bu çeşitli görevlerin dışında sekonder metabolitler antibiyotik, kemoterapötik, pestisid, immünsüpresif, antilipolitik ajan gibi çok çeşitli farmasötik fonksiyonlara da sahiptir ve bu etkileri nedeniyle yaygın şekilde kullanılmaktadır . Fonksiyonlarındaki çeşitliliğe benzer şekilde, bu bileşikler kimyasal yapıları bakımından da çok büyük çeşitlilik gösterirler. Bu makalede, ribozom dışı yolla sentezlenen oligopeptid yapısındaki sekonder metabolitler (nonribozomal peptidler) ele alınacak ve sentezlenme mekanizması incelenecektir.

Bladder carcinoma is among the most frequent cancer types especially among men. Intravesical instillation of attenuated strain of Mycobacterium bovis, Bacillus Calmette-Guerin is the standard treatment of medium and high risk patients. It is thought that the effect is through stimulation of the immune system. Since, the use of live mycobacteria may yield to deathly side effects, intensive research is in progress to obtain more potent and less harmful treatment alternatives. Applications of mycobacteria together with other immunostimulants, use of genetically modified organisms, or use of nonpathogenic strains such as Mycobacterium phlei are examples to such researches. Cell wall is sufficient for antitumoral activity. Our research group investigated the immunostimulating activity of several cell wall subfractions of Mycobacterium phlei and showed that the heat stable, water soluble structures, instable to protein denaturating agents and do not contain DNA might be responsible for these effects. Next, immunostimulating activity of 88 mycobacteria strains were investigated and found out that 12 nonpathogenic, rapid growing strains might be an alternative to Mycobacterium phlei. Separation of the cell wall components of these strains by multidimensional HPLC and identification of the structures is in progress. The findings so far obtained resemble the findings obtained with Mycobacterium phlei. More detailed peptidomics and proteomics studies to isolate and characterize these structures may shed light on the mechanism of action of these components and lead to preparation of less harmful antitumoral agents. Further study with animal models is also required to show the in vivo effects of these substances.

Some lipodepsipeptides produced by Pseudomonas syringae pv. syringae showed strong antimycobacterial activity towards Mycobacterium smegmatis. MIC values found were between 1.5-3.2 microg/ml, which is comparable to some primary drugs for tuberculosis. Among the lipodepsipeptides, Syringomycin E (SRE) appears to be the most potent antimycobacterial agent.

The purpose of this study was to investigate the influence of clozapine on plasma serotonin, platelet serotonin and monoamine oxidase (MAO) levels in schizophrenic patients and to compare their results with those of unmedicated healthy controls. Groups of 20 outpatients ...

The aim of this study was to investigate the relationship between penile color Doppler sonography (CDS) findings and sonographic endothelial parameters in patients with erectile dysfunction (ED), including intima-media thickness (IMT) of common carotid arteries (CCA) and flow-mediated dilatation (FMD) of brachial artery. Fifty-six ED patients were included in the study. Penile CDS, IMT of CCA and FMD of brachial artery were performed in all patients. According to penile CDS findings, 27 (48%) patients had non-vasculogenic and 29 (52%) patients had vasculogenic ED. Among 29 patients, 17 (30%) patients had cavernous veno-occlusive disease (CVOD) and 12 (22%) patients had arterial/combined insufficiency (AI). Median (interquartile range) FMD values of nonvasculogenic ED, CVOD and AI were 12.50 (6.54)%, 12.82 (7.41)% and 6.25 (7.17)%, respectively. FMD was found to be impaired significantly in AI group when compared to the other groups. FMD values of CVOD group were lower when compared to non-vasculogenic group, but the difference was not statistically significant. IMT values of vasculogenic ED patients were higher than nonvasculogenic ED patients (Po0.05). Although IMT values were higher in AI group when compared to CVOD, the difference was not statistically significant. The combined use of IMT and FMD established the diagnosis of vasculogenic ED with 100% sensitivity and 59.2% specificity. The positive predictive value was 72%, negative predictive value 100% and accuracy 80%. The combined use of brachial artery FMD and carotid arteries IMT measurements may be suggested as an alternative method to evaluate vasculogenic ED.

Reactive oxygen species (ROS) may be involved in the toxicity of chlorpyrifos-ethyl (CE) [O,O-diethyl-O-(3,5,6-trichloro-2-pyridyl)phosphorothioate]. We have, therefore, examined the in vivo effects of CE on the rat erythrocyte antioxidant system and evaluated the ameliorating effects of melatonin and a combination of vitamin E and vitamin C on the oxidative damage induced by CE. The experimental groups were: (1) control group, (2) CE-treated group (CE), (3) vitamin E plus vitamin C treatment group (Vit), (4) melatonin-treated group (Mel), (5) vitamin E plus vitamin C plus CE treatment group (Vit + CE), and (6) melatonin plus CE treatment group (Mel + CE). Vitamin E and vitamin C were administered intramuscularly once a day for 6 consecutive days at 150 and 200 mg/kg, respectively, in the Vit and Vit + CE groups. Melatonin was administered intramuscularly at 10 mg/kg per day for 6 consecutive days in the Mel and Mel + CE groups. At the end of the fifth day, the rats of CE, Vit + CE and Mel + CE groups were treated orally with the first of two equal doses of 41 mg/kg CE, the second oral dose being given 21 h later. Blood samples were taken 24 h after the first CE administration. Levels of thiobarbituric acid reactive substance (TBARS), antioxidant defence potential (AOP), and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were determined in erythrocytes. In comparison with the control group, oral administration of CE significantly (P < 0.05) stimulated TBARS activity while significantly (P < 0.05) inhibiting AOP and the activities of SOD and CAT. However, GSH-Px activity remained unchanged by CE treatment. Treatment with melatonin and vitamins E plus C significantly (P < 0.05) reduced the CE-induced increase of TBARS, and overcame the inhibitory effect of CE on SOD and CAT, but not on AOP. Melatonin treatment significantly (P < 0.05) increased only GSH-Px activity, irrespective of the effect of CE. These results suggest that CE treatment increases in vivo lipid peroxidation and decreases antioxidant defence by increasing oxidative stress in erythrocytes of rats, and melatonin and a combination of vitamin E and vitamin C can reduce this lipoperoxidative effect.

The effect of cigarette smoke on lipid peroxidation and antioxidant enzymes such as catalase, superoxide dismutase, glutathione peroxidase and on the concentration of N-methyl-d-aspartate receptor (NMDAR) subunits 2A and 2B in the hippocampus of Sprague-Dawley rats exposed to cigarette smoke for 2h/day for a period of 4 weeks was determined. It was observed that NMDAR 2A and 2B concentrations in the hippocampus were enhanced in the case of animals exposed to cigarette smoke, whereas lipid peroxidation and antioxidant enzyme activities did not show any change as compared to control animals. The results of our study suggest that cigarette smoke induces NMDAR 2A and 2B expression in the hippocampus, and that this is not due to an increased lipid peroxidation, because cigarette smoke has no effect on lipid peroxidation and antioxidant enzyme activities in the hippocampus.

O,O-dimethyl ester is the organophosphate insecticide (OPI) most commonly used worldwide in the pest control of crops. Subchronic MD exposure was evaluated for its effects on lipid peroxidation, the serum activities of cholinesterase (ChE), and enzymes concerning liver damage, and the protective effects of combination of vitamins E and C in albino rats. Additionally, the histopathological changes in liver tissue were examined. Experimental groups were as follows: control group; a group treated with 5 mg/kg body weight MD (MD group); and a group treated with 5 mg/kg body wight MD plus vitamin E plus vitamin C (MD+AO group). The MD and MD+AO groups were treated orally with MD on five days a week for 4 weeks. The serum activities of cholinesterase (ChE), alanine transferase (ALT), aspartate amiotransferase (AST), lactate dehydrogenase (LDH), γ -glutamyltransferase (GGT), alkaline phosphatase (ALP), and the concentration of malondialdehyde (MDA) and liver histopathology were studied. In serum samples, MD significantly increased MDA concentration and ALP, AST, GGT, LDH activities but decreased the ALT and ChE activities. In the MD+AO group, MDA level and ALP, AST, LDH activities were significantly decreased and ChE activity was increased compared to the MD group. Histopathological changes found in liver tissue of rats treated with MD included were infiltration with mononuclear cells in all portal areas, sinusoidal dilatation, and focal microvesicular steatosis and hydropic degenerations in parenchymal tissue. The severity of these lesions was reduced by administration of vitamins. From these results, it can be concluded that subchronic MD causes liver damage, and lipid peroxidation may be a molecular mechanism involved in MD-induced toxicity. Furthermore, the combination of vitamins E and C can reduce the toxic effects of MD on liver tissue of rats.

1. Fluoride (F) is an essential trace element that has protective effects against bone mineral loss. However, it becomes toxic at higher doses and induces some adverse effects on a number of physiological functions, including reproduction. The aims of this study were to examine F-induced oxidative stress that promotes production of reactive oxygen species (ROS) and to investigate the role of vitamins C and E against possible F-induced endometrial impairment in rats.

The aim of the present study was to determine the effects of aging and dementia of the Alzheimer type (DAT) on lipid peroxidation and antioxidant enzyme activities. Twenty-six patients with DAT were included in the present study. Group I: 26 patients diagnosed as DAT and studied 5 yr ago. Group II: This group consisted of the same patients as Group I at the present time. Activities of CuZn superoxide dismutase (CuZn SOD) and glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) concentrations of these 26 subjects were measured and mini mental state examination (MMSE), brief psychiatric rating scale (BPRS), Hamilton depression rating scale (HDRS) were applied. The results revealed that 26 dementia patients had worsened cognitive symptoms and significantly increased CuZn SOD and MDA levels and decreased GSH-Px levels after 5 yr. Significant correlation was found between age and CuZn SOD (r: +0.406, p: 0.034), and between MMSE and MDA (r: -0.411, p: 0.032). We can conclude that MDA, CuZn SOD, and GSH-Px were significantly affected in the patients with Alzheimer disease. The most striking finding of this study is the significant correlation between MMSE and MDA in patients with DAT.

A variety of experimental studies have demonstrated the neuroprotective effects of melatonin, based on its antioxidant activity. In a prospective randomized study, the effects of melatonin were investigated in experimental head trauma-induced oxidative stress in rabbits. The experimental study was performed on 30 rabbits. The animals were divided into three groups. Group I (sham procedure): a right parietal craniotomy was performed on each animal, and the dura mater was left intact. Group II: experimental brain trauma (EBT) was performed on each animal using a 1 cm inner diameter x 10 cm long glass tube, through which a 20 g weight (0.5 cm diameter) was dropped onto the brain at the craniotomy site, causing a contusional head trauma. Group III: the same EBT model was performed, but 2.5 mg/kg melatonin was injected intraperitoneally four times (total dose 10 mg/kg); these injections were performed 20 min before the operation, during the trauma, 1 h later and 2 h later. The rabbits were sacrificed after the EBT at 24 h after the brain trauma. The activities of the three principal antioxidant enzymes-catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)-were determined, and the levels of malondialdehyde (MDA), a product of lipid peroxidation, and glutathione (GSH) were measured in brain homogenates. MDA levels were found to be higher in the EBT group than in the EBT+melatonin group or the sham procedure group. The SOD activity was found to be higher in the EBT group than in the sham procedure group. Enzymatic parameters (except for SOD) were significantly higher in melatonin-treated animals than in EBT animals. GSH levels in melatonin-treated animals were decreased compared with EBT animals. In conclusion, the data indicate that melatonin protects against free radical-mediated oxidative changes in brain tissue by boosting antioxidant enzymes, and in particular lowering lipid peroxidation in rabbits with EBT.