Medroxyprogesterone acetate induces c6 glioma chemosensitization via antidepressant-like lysosomal phospholipidosis/myelinosis in vitro

The authors have previously shown that medroxyprogesterone acetate (MPA) inhibits growth and increases drug sensitivity in C6 glioma with myeloid bodies. Myeloid bodies can occur in cells either due to robust toxicity with mitochondrial membrane disruption or due to milder events such as seen in lysosomal-phospholipidosis. Exact patterns of myelinosis accompanying to MPA chemo-sensitization is important, because uncoupling of nuclear versus mitochondrial toxicity of anti-neoplastics by MPA would lead to safer employment of glioma chemotherapy with reduced neurotoxicity. By monitoring and comparing cell kinetics with fine structural features of cell death, the authors estimated subcellular effects accompanying growth-inhibitory drug actions in C6 glioma. The analysis revealed that MPA induced mainly lysosomal phospholipidosis, while inhibiting clonogenicity alone and augmenting procarbazine efficacy. It induced apoptosis in combination with cisplatin. It reduced mitochondrial-damage-based early cytotoxicity of methotrexate, yet it did not hinder its anti-clonogenic efficacy. Progesterone analogues - similar to antidepressants - inhibit cholesterol esterification, and this efficacy relates with their P-glycoprotein inhibition. Reducing esterification and plasma-membrane localization of cholesterol may lead MPA induction of lysosomal phospholipidosis, growth indolency, and drug sensitization in glioma.     

Carotid hemodynamic parameters in hemodialysis patients

BACKGROUND: Atherosclerotic vascular disease is a major cause of morbidity and mortality for patients with end-stage renal disease on maintenance hemodialysis. Early atherosclerotic changes of the arterial wall can be evaluated by intima-media thickness (IMT), presence and structure of plaques and parameters of vascular resistance. The aim of the present study has been to investigate the relationship between carotid IMT and pulsatility index (PI) or resistive index (RI) values in hemodialysis patients. METHODS: We studied 36 hemodialysis patients (21 female, 15 male; median age 39.5 years, IQR 33.0-54.7 years) and 38 healthy volunteers (20 women, 18 men; median age 41.0 years IQR 32.5-53.5 years). All subjects underwent ultrasonography of common carotid artery, with determination of IMT, PI and RI. RESULTS: Bilateral and mean carotid IMT were found to be significantly higher in hemodialysis patients than in the control group (P<0.0001). Right and left carotid artery RI values were determined to be lower in hemodialysis patients than in the control group (P=0.007 for both). Similarly, right and left carotid PI values were also determined significantly lower in the hemodialysis group (P=0.005 and P=0.004, respectively). There was a moderate negative correlation between the right carotid IMT and right PI (r=-0.258, P=0.026). CONCLUSIONS: In contrast to previous studies in patients with diabetes, hypertension or cerebrovascular disease, PI and RI values decrease when IMT increases in hemodialysis patients. This finding may be a result of peripheral vasodilatation secondary to anemia in hemodialysis patients.     

Reduced urinary excretion of homocysteine could be the reason of elevated plasma homocysteine in patients with psychiatric illnesses

ObjectivesAlthough increased plasma total homocysteine (tHcy) concentrations were reported in psychiatric diseases, currently the reasons of elevated tHcy levels were not clearly understood. In this study we aimed to investigate the contribution of renal clearance of homocysteine on plasma tHcy load in patients with depression and first episode psychosis.Design and methodsThirty depression, 14 first episode psychosis patients and 34 healthy individuals (control group) were involved in the study. In patients and control groups, plasma and urine tHcy levels, urine methylmalonic acid (uMMA), serum vitamin B12 and folate concentrations were measured.ResultsAlthough there was not any difference between depression, psychosis and control groups with respect to mean (SD) values of vitamin B12 (289(131), 230 (72) and 249(79) pg/mL, respectively) and folate (6.4(4.0), 5.3(2.3) and 5.7(2.3) ng/mL, respectively), plasma tHcy levels of depression and psychosis group were higher than the control values (16.3(6.2), 15.5(4.3) and 9.9(2.1) μmol/L, respectively). Urine tHcy values of patient groups were significantly lower than those in the control group (14.5(7.6), 15.8(6.8) and 29.6(16.9) μmol/g creatinine, respectively). There were elevated uMMA levels in depression and psychosis groups compared with control group (4.9(2.4), 6.6(3.2) and 2.8(1.2) mmol/mol creatinine, respectively). There were a significant and negative correlation between urinary tHcy and plasma tHcy levels (r = ? 0.258 and p = 0.011).ConclusionIn conclusion, reduced urinary tHcy levels in psychiatric patients could be one of the reasons of plasma tHcy elevations with normal folate and vitamin B12 levels. Altered renal handling mechanisms of homocysteine may lead to elevated plasma tHcy levels by reduced clearance of homocysteine via glomerular filtration.     

Prolidase activity in serum and pleural fluids in patients with tuberculous pleural effusion [correction of effussion

Objectives

Pleural tuberculosis, which is present in around 4% of all tuberculosis cases may resolve spontaneously or associated with progressive disease and a high recurrence rate. Recently upon exposed to cytokines and bacterial products, mesothelium has been shown to produce collagen that may be involved in pleural inflammatory responses. Prolidase is involved in the final stage of degradation in collagen catabolism. In this study we aimed to evaluate pleural fluid and serum prolidase activities in patients with tuberculous (TB) pleurisy and compared with those in non-tuberculous (non-TB) pleural effusions.

Design and methods

21 patients with tuberculous (TB) pleurisy (11 F/10 M), ages 35-52 (median 44) and 22 patients (10 F/12 M), ages 41-63 (median 52) with non-tuberculous pleurisy included as non-tuberculous (non-TB) pleurisy group consecutively referred to our pulmonary clinic for evaluation. Serum and pleural prolidase activities in 21 TB and 22 non-TB pleurisy patients were analyzed by photometric method.

Results

Prolidase enzyme activities in serum and pleural fluids of TB group (1072 ± 171 and 1392 ± 215 U/L, respectively) were significantly higher than those values in non-TB group (787 ± 144 and 943 ± 174 U/L, respectively). Prolidase activities in pleural fluid were significantly higher than those in serum in both groups. There was a significant positive correlation between pleural and serum prolidase activities in TB group (r = 0.579 and p = 0.006) and in non-TB group (r = 0.858 and p < 0.001). In Receiver Operating Characteristic (ROC) analysis, sensitivity and specificity values were 86% and 82% for a cut-off value of 1130 U/L for pleural prolidase activity and were 81% and 82% for a cut-off value of 952 U/L for serum prolidase activity, respectively.

Conclusion

In conclusion, there is an elevated pleural fluid and serum prolidase enzyme activity in patients with TB pleurisy compared with non-TB pleurisy group. The higher enzyme activities in TB group might reflect increased collagen turnover in those patients.     

PON1 activity and total oxidant status in patients with active pulmonary tuberculosis

OBJECTIVES: The aim of this study was to the investigate effect of tuberculosis infection on paraoxonase-1 (PON1) activity and oxidative status in patients with pulmonary tuberculosis (PTB). DESIGN AND METHODS: Twenty-five active PTB subjects and 33 healthy controls were included in the study. Serum PON1 activity, total oxidant status (TOS), lipid hydroperoxide (LOOH) and total free sulfydryl (-SH) groups were determined. RESULTS: Serum basal/salt-stimulated paraoxonase activities, arylesterase activity and total -SH group levels were significantly lower in patients with PTB than controls (p<0.05, p<0.05, p<0.001 and p<0.01 respectively), while TOS and LOOH levels were significantly higher (p<0.01 and p<0.05, respectively). In PTB patients, TOS, LOOH and total -SH group levels were significantly correlated with paraoxonase (r=-0.371, p<0.05; r=-0.286, p<0.05; r=0.625 p<0.01; respectively) and arylesterase (r=-0.437, p<0.01; r=-0.352, p<0.05; r=0.653, p<0.01; respectively). CONCLUSIONS: Patients with active PTB are exposed to potent oxidative stress and they have decreased PON1 activity. These predisposal factors may, in part, play a role in the pathogenesis of atherosclerosis in PTB.     

Unusual Congenital Aortic Anomaly with Rare Common Celiamesenteric Trunk Variation: MR Angiography and Digital Substraction Angiography Findings

Magnetic resonance angiography and digital substraction angiography (DSA) findings in a case with a rare congenital thoracoabdominal aortic hypoplasia and common celiamesenteric trunk variation with occlusion of infrarenal abdominal aorta are described here. To our knowledge, this aortic anomaly has not been previously described in the English literature. DSA is the optimum imaging modality for determination of aortic hypoplasia, associated vascular malformations, collateral vessels, and direction of flow within vessels.     

Determinants of protection against diphtheria in adult hemodialysis patients

Diphtheria is of great epidemiological concern. Although mainly observed during childhood, unvaccinated adults and relatively immunocompromised patients are at increased risk for acquiring diphtheria. We aimed to determine the rates and certain determinants of protection against diphtheria in adult hemodialysis (HD) patients. Protection rates of 322 HD patients were compared with 65 diabetes mellitus type 2 (DM) patients and 65 healthy controls. A questionnaire was held in regard to smoking habits and alcohol intake. Antibody levels against diphtheria were assessed by an in-house ELISA and a concentration of >or=0.1 IU/mL was regarded as protective. Effects of age, gender and time being on dialysis on protection were assessed by logistic regression. Ratios of individuals with protective antibody levels were found to be 36% (116/322), 27.7% (18/65), and 52.3% (34/65) for HD, DM, and control groups, respectively. Hemodialysis patients had a significantly (p < 0.05) lower protection rate than healthy controls. In all study groups, there was a tendency of higher protection rate with increasing age. These low ratios of protected individuals in both HD and DM patient groups are alarming, as these patients generally have defects in vaccine responses, and carriage is important in the perpetuation of diphtheria. The protection status of these patient groups might be improved with additional vaccinations.     

Comparison of the effects of desflurane and sevoflurane on the expression of platelet surface glycoproteins in unstimulated and adenosine diphosphate-induced platelets in vitro

STUDY OBJECTIVE: To compare the effects of one minimum alveolar concentration (MAC) desflurane and sevoflurane on the expression of CD42b (glycoprotein [GP] Ib), CD41 (GPIIb), CD61 (GPIIIa), CD62P (P-selectin), and CD63 in both unstimulated and adenosine diphosphate (ADP)-stimulated platelets in vitro. SETTING: University laboratory. SUBJECTS: 15 healthy volunteers. INTERVENTIONS: Platelet-rich plasma was obtained and divided into three groups: platelet-rich plasma exposed to air (group 1); air plus one MAC desflurane (6% vol; group 2), and air plus one MAC sevoflurane (2% vol; group 3), for 40 minutes. Percentage of antigen-positive cells (%(+)) mean channel fluorescence (MCF(Sigma)), and index of platelet activation for positive platelets (IPA(+)) as expression markers for GPIb, GPIIb, GPIIIa, P-selectin, and CD63, were measured. MEASUREMENTS AND MAIN RESULTS: In unstimulated platelets, expression markers for GPIIb and GPIIIa were significantly lower in groups 2 and 3 than group 1 (P < 0.001). P-selectin expression markers were significantly higher in group 2 than in group 1 or group 3 (P < 0.016). CD63 expression markers were significantly lower in group 3 than group 1 (P < 0.016). In ADP-stimulated platelets, expression markers for all glycoproteins were significantly higher in all groups. CONCLUSION: Neither one MAC desflurane nor sevoflurane showed any significant change in ADP-stimulated platelets compared with the control group.     

Protective effects of trimetazidine on testicular ischemia-reperfusion injury in rats

INTRODUCTION: We tried to prove the effectiveness of trimetazidine (TMZ) on testicular torsion-detorsion injury. MATERIALS AND METHODS: 15 male rats were equally divided into three groups: group 1 was the sham-operated control group; group 2 had 2 h of unilateral testicular ischemia followed by 3 days of reperfusion, and group 3 had 2 h of unilateral testicular ischemia followed by 3 days of oral TMZ treatment (5 mg/kg, bid) during reperfusion. In the removed testicles, tissue reduced glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx), malondialdehyde (MDA) levels and pathological modified Johnson scores (MJS) were evaluated. Mann-Whitney U test was used for statistical evaluations. RESULTS: In group 2, on the ipsilateral side, GSH were significantly lower and MDA were higher than in groups 1 and 3, though GSH and MDA were not statistically different between groups 1 and 3. On the other hand, GPx in the control testicles of group 3 was significantly lower compared to those in the counterparts of both groups 1 and 2. Among three groups, GR determined in both testicles were not statistically different. On the ipsilateral side, MJS in group 3 were lower than in the sham group, but significantly higher than in group 2. CONCLUSIONS: According to this study, TMZ has an antioxidant effect on testicular torsion-detorsion injury, though the protective effect of TMZ seems to decrease in control testicles. Consequently it has been considered that TMZ can be only used in torsion patients with a healthy contralateral testicle after further studies have been conducted.