Assessment of potential cardiovascular risk in trichloroethylene exposure by serum methylated arginine levels.

Trichloroethylene (TCE) is a widely used solvent in industrial applications and has toxic effects on various systems. Methylated arginine amino acids (eg asymmetric dimethyl arginine (ADMA), symmetric dimethyl arginine (SDMA)) cause the development of cardiovascular disease by inhibiting NO synthesis, which is considered to be heart-protector. The aim of this study is to determine the risk of cardiovascular diseases in TCE exposure by methylated arginine biomarkers. About 98 controls and 100 TCE-exposed male subjects were included in the study. Trichloroacetic acid (urinary metabolite of TCE), arginine, homoarginine, citrulline ADMA, SDMA, and N-monomethyl L-arginine (L-NMMA) levels were found significantly higher than control group (p < 0.001). The strongest correlation was found between ADMA and Trichloroacetic acid (TCA) level (r = 0.453, p < 0.01). Long-term TCE exposure, may be an important risk factor for cardiovascular diseases by increasing methylated arginine levels.

Assessment of Endothelial Dysfunction with Methylated Arginines and L-arginine in Cadmium-Exposed People: a Pilot Study.

BACKGROUND: Workers can be exposed to cadmium (Cd) in various industries. On the other hand, another potential source for Cd exposure is the food chain and smoking. Environmental pollution to Cd plays an important role in the development of atherosclerosis. Asymmetric dimethyl arginine (ADMA) levels promote the development of endothelial dysfunction and atherosclerosis-related diseases such as hypertension, acute coronary syndrome, congestive heart failure, and peripheral vascular diseases. The aim of this study is to evaluate the cardiovascular risks of non-symptomatic cadmium-exposed workers and to promote the value of methylated arginines in screening of toxic exposures. METHODS: A total 176 participants were included in the study which has been separated as control group (n = 79) and Cd-exposed group (n = 94). Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used for toxicological analysis of Cd levels. Also, liquid Chromatography-Mass Spectrometry (LC-MS/MS) was used for levels of methylated arginines such as ADMA, symmetric dimethylarginine (SDMA), NG-monomethyl-L-arginine (L-NM-MA), homoarginine, and citrulline. RESULTS: Statistically significant differences were observed for control and Cd-exposed groups, respectively as follows: Cd levels (0.25 ± 0.13 µg/L and 1.33 ± 0.61 µg/L), ADMA (0.16 ± 0.04 µmol/L and 0.22 ± 0.11 µmol/L), SDMA (0.21 ± 0.06 µmol/L and 0.27 ± 0.07 µmol/L), L-NMMA(0.02 ± 0.01 µmol/L and 0.03 ± 0.01µmol/L), and arginine/ADMA levels (695.82 ± 620.63 and 478.30 ± 432.61). CONCLUSIONS: Our results suggest that workers chronically exposed to Cd showed imbalances in endothelial parameters.

Autoinhibitory Feedback Control over Photodynamic Action.

In biology, the activity of enzymes is usually regulated by feedback loops, which enables direct communication between enzymes and the state of the cell. In a similar manner, with the intention to have automated activity regulation, the therapeutic effect of a photosensitizer (BOD1) is shown to be reduced through a negative feedback loop initiated by the photosensitizer. Photodynamic action produces cytotoxic 1O2 and this reactive oxygen species reacts with ascorbate, generating H2O2. Peroxide-mediated oxidation of the photosensitizer auxiliary group leads to the formation of inactive BOD2 from the parent photosensitizer. BOD1 is shown to accumulate in mitochondria, and cell viability is shown to decrease significantly with BOD1 compared to the loop end product, BOD2. Photoinduced enhancement of fluorescence indicates the formation of inactive BOD2 under cellular conditions, and enhanced fluorescence acts as a reporter for the activity of the photosensitizer. We present the first example of PDT autoinactivation, and such a feedback control mechanism would enable a decrease in post-therapy side effects.

Effects of Glucose Ingestion on Serum Fractalkine Levels in Healthy Subjects and Newly Diagnosed Type 2 Diabetic Patients.

BACKGROUND: Fractalkine (FKN) is an inflammatory cytokine that has been shown with increased serum levels in diabetic patients and is considered to contribute to the adipose tissue inflammation by supporting monocyte adhesion to adipocytes which has an important role in the pathogenesis of type 2 diabetes mellitus (T2DM). Our aim was to evaluate the effects of glucose ingestion on the serum fractal - kine levels in healthy subjects with normal glucose tolerance (NGT) and newly diagnosed T2DM patients. METHODS: A total of 67 patients were included in this study, and they were divided into NGT (n=34) and T2DM (n=33) groups according to their oral glucose tolerance test (OGTT) results. The serum FKN and C-reactive protein (CRP) levels were measured at 0 and 120 minutes during an OGTT following overnight fasting. RESULTS: The 0-minute (basal) and 120-minute OGTT FKN levels were found to be significantly higher in the T2DM group when compared to the NGT group (p=0.012 and p=0.001, respectively). However, no significant differences were observed in terms of the changes in the basal and 120-minute OGTT FKN levels in the T2DM and NGT groups (p=0.433 and p=0.06, respectively). A significant positive correlation was observed between the 120-minute OGTT FKN and glucose levels in the study group consisting of all of the patients (r=0.331, p=0.006). CONCLUSIONS: In this study, basal and post-glycemic load FKN levels were found to be higher in newly diagnosed T2DM patients than those with NGT; however, there was no additional change in FKN levels by glycemic load.

The effects of melatonin and colchicine on ischemia-reperfusion injury in experimental rat testicular torsion model.

PURPOSE: The aim of the present study is to investigate the efficiency of colchicine and melatonin in an experimental rat testicular torsion model in the light of histological and biochemical data. METHODS: A total of 34 Wistar albino male rats were randomly divided into 5 groups as: Group C (control, n=6), Group S (sham; underwent only left scrotal exploration, n=7), Group TD (torsion and detorsion; 6h of ischemia and 7days of reperfusion, n=7), Group TD/M (TD+Melatonin; 6h of ischemia and 7days of reperfusion and 7days of 17mg/kg intraperitoneal melatonin per day, n=7), group TD/Col (TD+Colchicine; 6h of ischemia and 7days of reperfusion and 7days of 1mg/kg oral colchicine per day, n=7). Histopathologic evaluation of seminiferous tubule deterioration was performed by Johnsen's scoring system. Total antioxidant status (TAS), total oxidant status (TOS), IL-6, TNF alpha levels were analyzed in each group. RESULTS: The histopathologic scores, total antioxidant status (TAS), total oxidant status (TOS), IL-6, TNF alpha levels in groups C and TD/Col were significantly lower than groups TD and TD/M (P<.001). CONCLUSION: Our study results revealed that colchicine reduced testicular ischemia-reperfusion injury in experimental rat testis torsion model. Although detorsion of testis is crucial for the preserving the testicular viability, antioxidant and anti-inflammatory treatment modalities like colchicine might help to reduce ischemia-reperfusion injury in detorsed testis.

Assessment of In vitro Antibacterial Activity and Cytotoxicity Effect of Nigella sativa Oil.

BACKGROUND: Methicillin resistance is a serious health concern since it has spread among Staphylococcus aureus and coagulase-negative Staphylococci (CoNS) that are frequent community and nosocomial pathogens worldwide. Methicillin-resistant strains are often resistant to other classes of antibiotics, making their treatment difficult. Nigella sativa oil is known to be active against Gram-positive cocci, yet its in vitro cytotoxicity is rarely investigated, is a proper and powerful candidate for treatment of methicillin-resistant isolates. OBJECTIVES: The aim of this study is to evaluate the in vitro antibacterial activity and cytotoxicity effect of N. sativa oil. MATERIALS AND METHODS: The minimal inhibitory concentrations (MICs) of N. sativa oil were determined by broth microdilution method against four different American Type Culture Collection strains, 45 clinical isolates of methicillin-resistant S. aureus (MRSA), and 77 methicillin-resistant CoNS (MRCoNS). The effects of different dilutions (0.25 µg/mL, 0.5 µg/mL, and 1 µg/mL) of N. sativa oil on the proliferation of gingival fibroblasts were evaluated. RESULTS: The MIC values of N. sativa oil against clinical isolates of Staphylococci were between <0.25 µg/mL and 1.0 µg/mL. Compared to the control group, there was no cytotoxic effect on the proliferation of the gingival fibroblasts. CONCLUSION: In the present study, the oil of N. sativa was very active against MRSA and MRCoNS and had no in vitro cytotoxicity at relevant concentrations. These findings emphasize that there is a requirement for further clinical trials on N. sativa oil for "safe" medical management of infections caused by methicillin-resistant Staphylococci. SUMMARY: The minimal inhibitory concentration (MIC) values of Nigella sativa oil against Staphylococcus aureus American Type Culture Collection (ATCC) 29213, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853 standard strains were 0.5 µg/mL, 2 µg/mL, 64 µg/mL, and 64 µg/mL, respectivelyThe N. sativa oil showed an excellent antibacterial activity against clinical isolates of methicillin-resistant S. aureus and methicillin-resistant coagulase-negative Staphylococci with very low MIC range of <0.25-1.0 µg/mLThe N. sativa oil exhibited no cytotoxic effect on the proliferation of the gingival fibroblasts. Abbreviation used: ATCC: American Type Culture Collection; CLSI: Clinical and Laboratory Standards Institute; CoNS: Coagulase-negative Staphylococci; DMEM: Dulbecco's modified Eagle's medium; DMSO: Dimethyl sulfoxide; FBS: Fetal bovine serum; HGF: Human gingival fibroblast; MIC: Minimal inhibitory concentration; MRCoNS: Methicillin-resistant CoNS; MRSA: Methicillin-resistant S. aureus.