Plasma malondialdehyde and serum trace element concentrations in patients with active pulmonary tuberculosis

Increased amounts of reactive oxygen species (ROS) are produced as a consequence of a phagocyte respiratory burst during pulmonary inflammation. The aim of our study was to assess the concentration of malondialdehyde (MDA) and trace metals in patients with active pulmonary tuberculosis (TB). Eighty-three subjects were enrolled into the study and prospectively divided into three groups: 22 subjects with healthy controls (group I), 21 patients with inactive pulmonary TB (group II), and 40 patients with active pulmonary TB (group III). Before beginning the therapy, plasma MDA and serum concentrations of zinc (Zn), copper (Cu), albumin, and iron (Fe) were measured. The concentration of MDA and Cu in group III were higher than in the other groups (p<0.0001). The serum Zn and albumin levels were significantly lower in group III compared with healthy controls (p<0.05). There was a positive correlation between MDA and erythrocyte sedimentation rate (r=+0.647, p<0.0001; Spearman’s test). Our data indicated increased circulating levels of MDA and changed serum trace metal levels in active pulmonary TB. Trace metal levels must be closely followed during the diseases process and further studies are needed to assess the role of antioxidants as adjuvant therapy in patients with active pulmonary TB.     

Helicobacter pylori infection in Turkish children: comparison of diagnostic tests, evaluation of eradication rate, and changes in symptoms after eradication

BACKGROUND: Helicobacter pylori infection is most frequently acquired in childhood. After this organism is eradicated, the rate of reinfection is low. Thus, it is very important to diagnose and treat the disease appropriately in childhood, and to be able to assess eradication with certainty. Eradication of H. pylori infection is reported to reduce or eliminate abdominal pain and dyspeptic symptoms in children. PATIENTS AND METHODS: The study involved 102 children who had already been diagnosed with symptomatic H. pylori infection based on gastric histopathological examination, urea breath test, rapid urease test, serology and culture. Each patient's symptoms and family history of gastrointestinal problems were recorded. Using histology as the gold standard for identifying H. pylori infection, we determined the diagnostic sensitivity of each of the other methods. Omeprazole or lansoprazole, amoxicillin and clarithromycin were administered as eradication treatment, and each patient was re-evaluated by urea breath test 8 weeks later. Each child was re-interviewed about symptoms after treatment. These answers and the results of drug sensitivity testing were recorded. Cases of failed eradication were re-treated with a quadruple-drug regimen of tetracycline, metronidazole, bismuth subsalicylate and omeprazole. RESULTS: The most frequent symptom was abdominal pain (89.2%). Fifty-four per cent of the subjects had a family history of dyspeptic symptoms. Sixty-six patients (64.7%) exhibited nodularity in the antral mucosa. The sensitivities of the diagnostic tests in histologically proven cases were as follows: urea breath test 100%, rapid urease test 89.2%, serology 71.9%, and culture 54.9%. Metronidazole had the highest frequency of resistance (36.4%) and the rate of clarithromycin resistance was 18.2%. The eradication rate after first-line therapy was 75.5%, and abdominal pain and dyspeptic symptoms were reduced or completely resolved in 75.7% of the successful-eradication cases. The proportion of failed-eradication cases that responded well to quadruple-drug therapy was 93.8%. CONCLUSION: Symptomatic H. pylori infection in a child should always be treated. The urea breath test is an accurate and reliable way to identify H. pylori-positive patients and to determine the response to treatment. Triple-agent therapy is effective for eradicating H. pylori infection in children and usually helps reduce or eliminate dyspeptic symptoms. The level of H. pylori resistance to metronidazole is high in our region. The significant rate of resistance to clarithromycin (18.1%) may explain the treatment failure observed in this study.     

The effect of hyperbaric oxygen on neuroregeneration following acute thoracic spinal cord injury

AimsAlthough hyperbaric oxygen (HBO) treatment following spinal cord injury (SCI) have been studied in terms of neurological function and tissue histology, there is a limited number studies on spinal cord tissue enzyme levels.Main methodsThe effect of HBO treatment in SCI was investigated by measuring superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), nitric oxide synthase (NOS) and nitric oxide (NO) activity in the injured tissue. SCI was induced by applying an aneurysm clip extradurally at the level of T9-T11 vertebrae. Preoperative HBO (preopHBO) treatment was applied for 5 days and postoperative HBO (postopHBO) for 7 days.Key findingsIn the preopHBO group, a significant decrease was observed in NOS and NO compared to the SCI group. There was a decrease in SOD, NOS and NO in the postopHBO group when compared to the SCI group. In the pre–postHBO group SOD, GPx, NOS and NO decreased significantly. There was a decrease in SOD in postopHBO compared to preopHBO. In the prepostopHBO, SOD decreased significantly compared to that in the preopHBO group. The prepostopHBO presented a significant decrease in GPx compared to postopHBO (p < 0.05 for all parameters). No significant difference was observed for catalase for all groups. Significant improvement was found in BBB scores for both postopHBO and prepostHBO groups when compared to the SCI group (p < 0.05).SignificanceHBO treatment was found to be beneficial following SCI in terms of biochemical parameters and functional recovery in the postoperative period.     

Sequence-defined glycopolymer segments presenting mannose: synthesis and lectin binding affinity

We present for the first time the synthesis of sequence-defined monodisperse glycopolymer segments via solid-phase polymer synthesis. Functional building blocks displaying alkyne moieties and hydrophilic ethylenedioxy units were assembled stepwise on solid phase. The resulting polymer segments were conjugated with mannose sugars via 1,3-dipolar cycloaddition. The obtained mono-, di-, and trivalent mannose structures were then subject to Con A lectin binding. Surface plasmon resonance studies showed a nonlinear increase in binding regarding the number and spacing of sugar ligands. The results of Con A lectin binding assays indicate that the chemical composition of the polymeric scaffold strongly contributes to the binding activities as well as the spacing between the ligands and the number of presented mannose units. Our approach now allows for the synthesis of highly defined glycooligomers and glycopolymers with a diversity of properties to investigate systematically multivalent effects of polymeric ligands.     

Purification and cDNA cloning of a novel neurotoxic peptide (Acra3) from the scorpion Androctonus crassicauda

Androctonus crassicauda is one of the Southeastern Anatolian scorpions of Turkey with ethno-medical and toxicological importance. Two toxic peptides (Acra1 and Acra2) were isolated and characterized from the venom of this scorpion. In this communication, the isolation of an additional toxin (Acra3) by chromatographic separations (HPLC and TSK-gel sulfopropyl) and its chemical and functional characterization is reported. Acra3 is a 7620Da molecular weight peptide, with 66 amino acid residues crosslinked by four disulfide bridges. The gene coding for this peptide was cloned and sequenced. Acra3 is anticipated to undergo post-translational modifications at the C-terminal region, having an amidated serine as last residue. Injection of Acra3 induces severe neurotoxic events in mice, such as: excitability and convulsions, leading to the death of the animals within a few minutes after injection. Electrophysiological assays conducted with pure Acra3, using cells that specifically expressed sodium channels (Nav1.1-Nav1.6) showed no clear effect. The exact molecular target of Acra3 remained undiscovered, similar to three other scorpion peptides that clustered very closely in the phylogenetic tree included here. The exact target of these four peptides is not very clear.     

Rosiglitazone treatment reduces hippocampal neuronal damage possibly through alleviating oxidative stress in chronic cerebral hypoperfusion

Oxygen free radicals and lipid peroxidation may play significant roles in the progress of injury induced by chronic cerebral hypoperfusion of the central nervous system. Rosiglitazone, a well known activator of PPARγ, has neuroprotective properties in various animal models of acute central nervous system damage. In the present study, we evaluate the possible impact of rosiglitazone on chronic cerebral hypoperfused-rats in regard to the levels of oxidative stress, reduced glutathione, and hippocampal neuronal damage. Chronic cerebral hypoperfusion was generated by permanent ligation of both common carotid arteries of Wistar rats for one month. Animals in treatment group were given rosiglitazone orally at doses of 1.5, 3, or 6mg/kg per day of the 1month duration. The treatment significantly lowered the levels of both malondialdehyde and neuronal damage, while elevated the reduced glutathione level markedly. These findings suggest that the beneficial effect of rosiglitazone on hypoperfusion-induced hippocampal neuronal damage might be the result of inhibition of oxidative insult.     

Betaine prevents loss of sialic acid residues and peroxidative injury of erythrocyte membrane in ethanol-given rats

To evaluate chronic ethanol toxicity on erythrocyte membrane and preventive action of betaine as a methyl donor, 24 male Wistar albino rats were divided into three groups: control, ethanol and ethanol plus betaine group. Animals were fed 60 ml diet per day for two months. Rats in the ethanol group were fed ethanol 8 g/kg/day. The ethanol + betaine groups were fed ethanol plus betaine (0.5% w/v). After two months, all animals were killed. Malondialdehyde (MDA) and sialic acid (SA) levels were determined in plasma samples. Osmotic fragility tests were performed on whole blood samples and erythrocyte membrane thiol contents were determined using membrane suspensions. Plasma MDA levels in ethanol-given rats were increased significantly compared to the control group of rats (p < 0.05). MDA in the betaine group was significantly lower than that in the ethanol group (p < 0.05). Erythrocyte membrane thiol contents in ethanol group were decreased compared with those of the control group (p < 0.05). Thiol contents were increased slightly after betaine therapy, but this increase was not statistically significant (p > 0.05). Plasma sialic acid levels in the ethanol group were significantly higher than in the control group (p < 0.05). Sialic acid was decreased in the betaine group compared to the ethanol group (p < 0.05). In the osmotic fragility test, we observed that chronic ethanol consumption increased erythrocyte hemolysis. Betaine protected against ethanol-induced hemolysis. Our findings show that chronic ethanol administration affects erythrocyte membrane properties and this may be related to oxidative stress. Betaine protects erythrocyte membrane alterations against chronic ethanol toxicity. Therefore betaine as a nutritional agent, may protect ethanol induced clinical problems associated with membrane abnormalities.     

Evaluation of biological effects induced by diagnostic ultrasound in the rat foetal tissues

In recent years, there has been growing interest in estimating the degree of heating caused by the diagnostic ultrasound in clinical practice. Both theoretical and experimental methods have been suggested for estimating the heating potential, or thermal hazard, of diagnostic ultrasound. Aim of this study was to evaluate in vivo effects of ultrasound exposure of variable duration (from 10 up to 20 min) with commercially available imaging systems commonly used for diagnostic imaging. Numerical results related to the thermal effect are obtained by simulation program based on B-mode (scanning) and Doppler (non-scanning). To investigate the biological effects of the ultrasound exposure to the brain and liver tissues, the antioxidant enzyme activity and thiobarbituric acid reactive substances (TBARS) of the tissues were evaluated. In liver tissue, as a lipid peroxidation index, TBARS levels very significantly increase in Doppler group compared to control. However, in B-mode, TBARS levels are the same with the control group. Use of B-mode in foetal tissue is more reliable than Doppler mode because temperature rise is very small compared to the Doppler mode. On the other hand, the antioxidant enzyme activities tend to increase in B-mode and Doppler groups compared to the control group as a defensive mechanism. In the brain tissue, lipid peroxidation is increased slightly in B-mode compared to the control group. This situation is related to the molecular structure of the brain tissue because of its high lipid concentration. In brain tissue, the antioxidant enzyme activities and lipid peroxidation were significantly increased, such as liver tissue in Doppler groups. Doppler ultrasound may produce harmful effects in rat foetus liver and brain tissues as a result of the high temperature rises.     

A novel mutation for TAP deficiency and its possible association with Toxoplasmosis

We describe two siblings (a male patient and his older sister) with a novel mutation in the peptide transporter associated to antigen processing (TAP). The index case presented with not only granulomatous skin lesions and recurrent sino-pulmonary infections, often associated with this deficiency, but also a severe pulmonary toxoplasmosis. His toxoplasmosis and skin lesions were successfully treated.     

Repulsive separation of the cytoplasmic ends of transmembrane helices 3 and 6 is linked to receptor activation in a novel thyrotropin receptor mutant (M626I)

Ligand-dependent activation of G protein-coupled receptors (GPCRs) involves repositioning of the juxtacytoplasmic ends of transmembrane helices TM3 and TM6. This concept, inferred from site-directed spin labeling studies, is supported by chemical cross-linking of the cytoplasmic ends of TM3 and TM6 blocking GPCR activation. Here we report a novel constitutive active mutation (M626I) in TM6 of the TSH receptor (TSHR), identified in affected members of a family with nonautoimmune hyperthyroidism. The specific constitutive activity of M626I, measured by its basal cAMP generation corrected for cell surface expression, was 13-fold higher than that of wild-type TSHR. Homology modeling of the TSHR serpentine domain based on the rhodopsin crystal structure suggests that M626 faces the side chain of I515 of TM3 near the membrane-cytoplasmic junction. Steric hindrance of the introduced isoleucine by I515 is consistent with the fact that shorter or more flexible side chains at position 626 did not increase constitutivity. Furthermore, a reciprocal mutation at position 515 (I515M), when introduced into the M626I background, acts as revertant mutation by allowing accommodation of the isoleucine sidechain at position 626 and fully restoring the constitutive activity to the level of wild-type TSHR. Thus, repulsive separation of the juxtacytoplasmic TM6 and TM3 in the M626I model conclusively demonstrates a direct link between the opening of this cytoplasmic face of the receptor structure and G protein coupling.