N‐acetyl cysteine attenuates diazinon exposure‐induced oxidative stress in rat testis

The aim of this study was to investigate the gonadotoxic effects of diazinon and its mechanism of action with special reference to its possible reactive oxygen species generating potential in rat testis and the protective effect of N‐Acetyl Cysteine (NAC) on the exposure of diazinon. The vehicle was given orally to the control group and NAC, diazinon, combination of NAC and diazinon were given to three treatment groups for 4 weeks. Testis lipid peroxidation levels were higher in diazinon group than in control although lipid peroxidation levels were lower in diazinon + NAC group than in diazinon group. The reduced glutathione (GSH) levels were lower in diazinon group than in control and NAC group although its levels were higher in diazinon + NAC group than in diazinon group. Vitamin C, Vitamin E and β‐carotene concentrations were also lower in diazinon group than in control and NAC groups. Vitamin E and β‐carotene concentrations were higher in diazinon + NAC group than diazinon group. Glutathione peroxidase activity and vitamin A concentrations in the testis did not show any difference between the four groups. In conclusion, we observed that NAC treatment modulated diazinon‐induced oxidative injury in the rat testis. These findings suggest that NAC supplementation can be useful in testis oxidative injury caused by the organophosphate insecticides.     

Lymph Node Ratio May Be Supplementary to TNM Nodal Classification in Node-positive Breast Carcinoma Based on the Results of 2,151 Patients

Background

The aim of the present study was to determine how lymph node ratio (LNR; the ratio of the number of metastatic lymph nodes to the number of removed lymph nodes) can supplement the TNM nodal classification in breast carcinoma.

Methods

We retrospectively reviewed the file records of 2,151 patients.

Results

Lymph node ratio-based low- (LNR ≤ 0.20), intermediate- (LNR 0.21–0.65), and high-risk (LNR > 0.65) patient groups had significantly different disease-free survival (DFS) (P < 0.001). The DFS of patients with N1, N2, and N3 disease was significantly different (P < 0.001). When LNR and TNM nodal groupings were included together in the Cox analysis, both groupings had independent prognostic significance (P < 0.001 and P < 0.001, respectively). The most significant LNR threshold value separating patients in low-risk and high-risk groups in terms of disease recurrence was 0.20 for N1 disease (P < 0.001), 0.35 for N2 disease (P < 0.001), and 0.90 for N3 disease (P < 0.001).

Conclusions

Lymph node ratio and TNM nodal groupings show no superiority over each other in categorizing patients with node-positive breast carcinoma into prognostic groups of low-, intermediate-, and high-risk. However, LNR grouping may supplement TNM nodal classification by categorizing patients within each TNM nodal group into low-risk and high-risk groups with significantly different survival.     

Epistasis effects of dopamine genes on interval timing and reward magnitude in humans

We tested human participants on a modified peak procedure in order to investigate the relation between interval timing and reward processing, and examine the interaction of this relation with three different dopamine-related gene polymorphisms. These gene polymorphisms affected the expression of catechol-o-methyltransferase, which catabolizes synaptic dopamine primarily in the prefrontal cortex (COMT Val158Met polymorphism), D2 dopamine receptors primarily in the striatum (DRD2/ANKK1-Taq1a polymorphism), and dopamine transporters, which clear synaptic dopamine in the striatum (DAT 3′ VNTR variant). The inclusion of these polymorphisms allowed us to investigate dissociable aspects of the dopamine system and their interaction with reward magnitude manipulations in shaping timed behavior. These genes were chosen for their roles in reward processing and cortico-striatal information processing that have been implicated for interval timing. Consistent with recent animal studies, human participants initiated their timed anticipatory responding earlier when expecting a larger reward in the absence of any changes in the timing of response termination or perceived time. This effect however was specific to two out of four evaluated COMT and DRD2 polymorphism combinations that lead to high prefrontal dopamine coupled with high D2 density and low prefrontal dopamine coupled with low D2 density. Larger rewards also decreased timing precision indices, some of which interacted with the COMT polymorphism. Furthermore, the COMT polymorphism that leads to higher prefrontal dopamine resulted in weaker manifestation of memory variability (relative to threshold variability) in timed behavior. There was no effect of DAT polymorphisms on any of the core behavioral measures. These results suggest that the reward modulates decision thresholds rather than clock speed, and that these effects are specific to COMT and DRD2 epistasis effects that presumably constitute a balanced prefrontal and striatal dopamine transmission.     

Increased pulse wave velocity and carotid intima–media thickness in patients with carpal tunnel syndrome

Introduction: Carpal tunnel syndrome (CTS) is associated with cardiovascular risk factors. The aim of our study was to determine whether carotid intima–media thickness (CIMT) and carotid–femoral pulse wave velocity (cf-PWV), as surrogates of cardiovascular disease and arterial stiffness, are increased in patients with carpal tunnel syndrome. Methods: Forty patients with CTS and 40 gender- and age-matched controls underwent cf-PWV assessment, CIMT measurement, and nerve conduction study. Results: CIMT and cf-PWV were increased significantly in patients with CTS. They correlated positively with median sensory and motor nerve distal latency. Whereas both CIMT and PWV related to CTS, only CIMT independently predicted CTS. Conclusions: There is both increased pulse wave velocity and CIMT and a positive correlation between these parameters and median nerve sensory distal latency in patients with CTS. CTS appears to be associated with arterial stiffness and atherosclerotic burden, but the underlying mechanisms require further study. Muscle Nerve 47: 872–877, 2013     

Evaluation of selective human MAO inhibitory activities of some novel pyrazoline derivatives

A series of 1-[2-((5-methyl/chloro)-2-benzoxazolinone-3-yl)acetyl]-3,5-diaryl-4,5-dihydro-1H-pyrazole derivatives were prepared by reacting 2-((5-methyl/chloro)-2-benzoxazolinone-3-yl)acetylhydrazine with appropriate chalcones. The chemical structures of all compounds were confirmed by elemental analyses, IR, ¹H NMR and ESI–MS. All the compounds were investigated for their ability to selectively inhibit monoamine oxidase (MAO) by in vitro tests. MAO activities of the compounds were compared with moclobemide and selegiline and all the compounds were found to inhibit human MAO-A selectively. The inhibition profile was found to be competitive and reversible for all compounds by in vitro tests. Among the compounds examined, compounds 5ae, 5af and 5ag were more selective than moclobemide, with respect to the K _i values experimentally found. In addition, the compound 5bg showed MAO-A inhibitor activity as well as moclobemide. A series of experimentally tested compounds (5ae–5ch) were docked computationally to the active site of the MAO-A and MAO-B isoenzyme. The AUTODOCK 4.01 program was employed to perform automated molecular docking.     

Synthesis, molecular modeling, and in vitro screening of monoamine oxidase inhibitory activities of some novel hydrazone derivatives

Thirteen 2-[2-(5-methyl-2-benzoxazolinone-3-yl)acetyl]-3/4/5-substituted benzylidenehydrazine derivatives were synthesized by reacting 2-(5-methyl-2-benzoxazolinone-3-yl)acetylhydrazine and substituted benzaldehydes in neutral and acid/base catalyzed conditions, and a comparison was made in terms of their yields and reaction times. The structures of all compounds were confirmed by IR, ¹H NMR, ¹³C NMR, mass spectral data, and elemental analyses. All the compounds were investigated for their ability to selectively inhibit MAO isoforms by in vitro tests and were found to inhibit recombinant human MAO-B selectively and reversibly in a competitive manner. Among the compounds examined, compound 16 was found to be more selective than selegiline, a known MAO-B inhibitor, in respect to the K _i values experimentally found. Additionally, compounds 9 and 15 showed moderate MAO-B inhibitor activity. The interaction of compounds with MAO isoforms was investigated by molecular docking studies using recently published crystallographic models of MAO-A and MAO-B. The results obtained from the docking studies were found to be in good agreement with the experimental values.