Genotoxic evaluation of welders occupationally exposed to chromium and nickel using the Comet and micronucleus assays

Chromium (Cr) and nickel (Ni) are widely used industrial chemicals. Welders in India are inclined to possible occupational Cr and Ni exposure. The carcinogenic potential of metals is a major issue in defining human health risk from exposure. Hence, in the present investigation, 102 welders and an equal number of control subjects were monitored for DNA damage in blood leucocytes utilizing the Comet assay. The two groups had similar mean ages and smoking prevalences. A few subjects were randomly selected for estimation of Cr and Ni content in whole blood by inductively coupled plasma mass spectrometry. The Comet assay was carried out to quantify basal DNA damage. The mean comet tail length was used to measure DNA damage. Welders had higher Cr and Ni content when compared with controls (Cr, 151.65 versus 17.86 micro g/l; Ni 132.39 versus 16.91 micro g/l; P < 0.001). The results indicated that the welders had a larger mean comet tail length than that of the controls (mean +/- SD, 23.05 +/- 3.86 versus 8.94 +/- 3.16; P < 0.001). In addition, the micronucleus test on buccal epithelial cells was carried out in a few randomly selected subjects. Welders showed a significant increase in micronucleated cells compared with controls (1.30 versus 0.32; P < 0.001). Analysis of variance revealed that occupational exposure (P < 0.05) had a significant effect on DNA mean tail length, whereas smoking and age had no significant effect on DNA damage. The current study suggested that chronic occupational exposure to Cr and Ni during welding could lead to increased levels of DNA damage.     

Genotypic analysis of Mycobacterium tuberculosis in Bangladesh and prevalence of the Beijing strain

Genotypic analysis was performed on 48 Mycobacterium tuberculosis complex strains collected from a hospital in Dhaka city. Deletion analysis showed that the isolates were all M. tuberculosis; 13 of them were found to be of the "ancestral" type, while 35 were of the "modern" type, indicating that both endemic (ancestral type) and epidemic (modern type) strains cause tuberculosis in Bangladesh. Genotyping based on the spoligotype and variable-number tandem repeats (VNTR) of mycobacterial interspersed repetitive units (MIRU) was also done. A total of 34 strains (71%) were grouped by spoligotyping into nine different clusters; the largest comprised 15 isolates of the Beijing genotype, whereas the remaining eight clusters consisted of two to five isolates. MIRU-VNTR typing detected 32 different patterns among 44 tested strains, and the 15 Beijing strains were further discriminated by MIRU-VNTR typing (7 distinct patterns for the 15 isolates). These results indicate that MIRU-VNTR typing, along with spoligotyping and deletion analysis, can be used effectively for molecular epidemiological studies to determine ongoing transmission clusters; to our knowledge, this is the first report about the type of strains prevailing in Bangladesh.     

The importance of cyclin D1 and Ki67 expression on the biological behavior of pancreatic adenocarcinomas

The aim of this study was to evaluate the role of cyclin D1 and Ki67 proteins involved in cell-cycle control as a prognostic factor in pancreatic carcinomas. We examined formalin-fixed, paraffin-embedded material from 59 pancreatic adenocarcinomas, for which appropriate clinical and prognostic data were available. The standard streptavidin biotin immunoperoxidase method was used for immunostaining with cyclin D1 and Ki67. The extent of positive nuclear and cytoplasmic cyclin D1 staining was graded semiquantitatively. Ki67 reactivity was quantified and expressed as the percentage of stained nuclei. Staining with cyclin D1 and Ki67 was compared with histopathological prognostic features, and their relation with survival was also tested statistically. Patients whose tumors were cyclin D1-positive showed perineural invasion significantly more frequently than did patients with cyclin D1-negative tumors at the immunohistochemical level. In addition, tumors with lymphatic vessel invasion and without showed a significant difference in terms of cytoplasmic cyclin D1 staining. Ki67 indices were statistically different in stage groups. There was a significant and direct correlation between Ki67 index and nuclear cyclin D1 staining scores. No relation with survival was found. Our results suggest that cell-cycle proteins do not directly affect the prognosis of patients with pancreatic adenocarcinoma. Conversely, cyclin D1-positive tumors tend to have perineural invasion more frequently. In addition, lymph vessel invasion is another factor related to cyclin D1 reactivity of the cells. Ki67 indices differ statistically in stage groups.     

Exhaled breath condensate MMP-9 level and its relationship wıth asthma severity and interleukin-4/10 levels in children

BackgroundMatrix metalloproteases (MMPs) are key mediators in airway remodeling, and MMP- 9 is the main type investigated to discover its implication for the pathogenesis and severity of asthma.ObjectiveTo evaluate MMP-9 and its natural tissue inhibitors of metalloproteinases (TIMP-1) levels of exhaled breath condensate (EBC) in children with asthma. We also analyzed any potential relationship between these enzymes and EBC interleukin (IL)-4/10 levels as well as asthma severity.MethodsThree study groups were formed: group 1, children with persistent asthma (n = 20); group 2, children with intermittent asthma (n = 10), and group 3, healthy controls (n = 12). Pulmonary functions were measured as forced expiratory volume in 1 second (FEV₁), peak expiratory flow (PEF), and forced expiratory flow from 25% to 75% of vital capacity values by spirometry, and MMP-9, TIMP-1 and IL-4/10 levels in EBC were analyzed by enzyme-linked immunosorbent assay (ELISA).ResultsThe MMP-9 levels of EBC were found to be 57.7 ± 17.5, 35.4 ± 11.7, and 30.6 ± 3.7 ng/mL in children belonging to group 1, group 2 and group 3, respectively. Children belonging to group 1 and group 2 showed significantly higher MMP-9 levels of EBC in comparison with the controls (P < .001 and P = .047, respectively). No statistically significant difference was found between groups regarding TIMP-1 levels of EBC. EBC MMP-9 levels were inversely correlated with both FEV₁ and PEF values (r = ?0.472, P = .011, and r = ?0.571, P = .002, respectively) in children with asthma. Positive correlations were also seen between MMP-9 levels and IL-4/10 levels of EBC (r = 0.419, P = .027 and r = 0.405, P = .032, respectively) in children with asthma.ConclusionWe showed that MMP-9 levels of EBC are elevated in children with asthma and correlated with lung functions and other inflammatory markers such as IL-4/IL10 in EBC.     

Endothelial molecules decipher the mechanisms and functional pathways in antibody-mediated rejection

Microvascular endothelium is the main target of injury in antibody-mediated rejection of human organ transplants. Hence, antibody-mediated rejection histologically presents with microvascular inflammation (pulmonary or myocardial or peritubular capillaritis, glomerulitis), thrombosis, and endothelial remodeling (duplication and/or multilayering of glomerular and capillary basement membranes). We previously observed upregulation of several endothelial genes in kidney transplant biopsies from patients with donor specific antibodies, indicating active antibody-mediated rejection and poor graft survival. Furthermore, endothelial molecular signals discovered a previously unknown clinical phenotype: C4d negative antibody-mediated rejection. With the recognition of C4d negative antibody-mediated rejection, data from multiple transplant centers now show that antibody-mediated rejection is the most common cause of late kidney transplant failure. This paper reviews the current understanding of endothelial cell biology in antibody-mediated rejection, emphasizing recent advances and pending questions. Furthermore, the paper discusses functionally active pathways in human antibody-mediated rejection, which include aspects of endothelial activation with increased endothelial adhesive and pro-coagulant signals facilitating leukocyte trafficking and attachment, cell-to-basement membrane interactions, platelet activation, coagulation, and endothelial repair responses. To understand effector mechanisms of antibody-mediated rejection and quantify the degree of antibody-mediated tissue injury in clinical transplants, endothelial cells provide a useful read-out.     

Improved cycle outcomes after laparoscopic ovarian diathermy in hyper-responder patients with previous ART failure

Excessive response to ovarian stimulation is common among hyper-responder patients undergoing assisted reproductive technology (ART). Cycle cancellations and severe ovarian hyperstimulation syndrome (OHSS) are all detrimental consequences observed within this cohort and several approaches have been proposed to enhance outcomes. The current study is designed to evaluate whether laparoscopic ovarian diathermy (LOD) improves ART outcomes and pregnancy rates by reducing Anti-mullerian hormone (AMH) levels in a group of patients who had a history of recurrent ART failure and high response. A total of 40 hyper-responder patients with history of previous ART failure were included. Group I consisted of 22 patients that underwent LOD prior to ART. Group II consisted of 18 patients that underwent only ART. Cycle outcomes of groups were compared. Following LOD, significant reduction in AMH levels were detected in group I (4.75?ng/mL to 2.25?ng/mL). Clinical pregnancies were similar among groups (40% versus 27.8% p?=?0.65). There was no cycle cancellation in Group I, whereas there were three cycle cancellations observed due to OHSS in Group II. Our results indicate that LOD might offer enhanced fertility outcomes and may reduce the likelihood of cycle cancellations in hyper-responders with previous ART failures.     

Impact of luteal phase hysteroscopy and concurrent endometrial biopsy on subsequent IVF cycle outcome

Purpose

Endometrial biopsy preceding implantation in in vitro fertilization (IVF) treatment causes a type of injury which facilitates implantation. Pre-treatment hysteroscopic evaluation of uterine cavity also raises the success in IVF. This study investigates whether office hysteroscopy and concurrent endometrial biopsy performed in the luteal phase, on the day of GnRH agonist initiation for long protocol, improves subsequent IVF outcome.

Methods

A prospective, nonrandomized, controlled study of 128 normoresponder women was performed: In 70 women (study group), office hysteroscopy and concurrent endometrial biopsy were performed on the day of GnRH agonist initiation preceding ET cycle and in 58 women (control group), GnRH agonist was initiated without any intervention. However, uterine cavity was shown to be normal with hysteroscopy within the previous 6 months in those women. Implantation and pregnancy rates were compared between the groups.

Results

Intrauterine pathologies were observed in 28 % of women in the study group. Implantation rate (38 vs. 25 %; p = 0.04) and pregnancy rate per ET (67 vs. 45 %; p = 0.01) were found to be significantly higher in the study group compared to the control group.

Conclusion

Office hysteroscopy and concurrent endometrial biopsy performed in the luteal phase, on the day of GnRH agonist initiation for long protocol, provide direct evaluation of the uterine cavity immediately before ET cycle and also significantly improve the implantation and IVF outcome.     

Survivin expression in non-small-cell lung carcinomas: correlation with apoptosis and other apoptosis-related proteins, clinicopathologic prognostic factors and prognosis.

The role of survivin that regulates the biological behavior of non-small-cell lung carcinoma (NSCLC) is still controversial. We aimed to investigate survivin expression in NSCLC and to define any correlation with expressions of p53, bcl-2, bax, apoptotic index (AI), tumor cell proliferation, clinicopathologic variables, and overall survival. Tumors of 63 patients with NSCLC were examined for expressions of survivin, p53, bcl-2, bax, and Ki-67 by immunohistochemistry. AI was also evaluated. Results for each antibody were correlated with each other, and with clinicopathologic variables including age, sex, histologic subtype, TNM (T: primary tumor, N: regional lymph node metastasis, M: distant metastasis) stage, lymph node status, smoking history, and prognosis. Nuclear survivin expression was inversely correlated with p53 expression (P = 0.04, r = - 0.367), and tumor stage (P = 0.03, r = - 0.273), and positively correlated with tumor cell proliferation (P = 0.009, r = 0.329). Cytoplasmic survivin expression positively correlated with smoking history (P = 0.02, r = 0.282). Survivin/bax ratio was inversely correlated with AI (r: - 0.004). By Kaplan-Meier analysis, TNM stage (P < or = 0.001), lymph node metastasis (P = 0.04), and Ki-67 index (P < or = 0.001) were associated with survival, whereas survivin was not. In multivariate analysis, only TNM stage was an independent predictor. Although survivin and other apoptosis-related protein expressions fail to predict the clinical outcome, the present findings suggest that survivin is involved in tumor cell apoptosis and proliferation and may play a role in critical steps of cancer progression in NSCLC.     

Sensitivity and specificity of Ankara University Cerebral Dominance Inventory in comparison with the Wada test

We aimed to examine the sensitivity and specificity of the Ankara University Cerebral Dominance Inventory (AUCDI) in determining left cerebral dominance compared with the Wada test. The AUCDI and Wada test were applied to 49 patients referred to Ankara University for epilepsy surgery. Hand, foot and ‘total’ preference scores were specified according to the results of the inventory. Thirty-eight of the patients had left cerebral dominance and 11 had atypical cerebral dominance for language. 86 % of the patients were right-handed and 43 % were right-footed. When compared with the results of the Wada test, the sensitivity of the AUCDI for each ‘total preference’, and hand and foot preference was 90, 95 and 50 % and specificity was 46, 46 and 82 %, respectively. The percentage of right-footed patients was low when compared with the other studies. This difference might result from the method used for assessing foot preference by the actual demonstration of the task rather than just asking about the performance. The AUCDI was found to be sensitive in terms of ‘total preference’ and hand preference, and specific in terms of foot preference for determining the left hemisphere dominance in patients preferring the right side. It was a cheap and noninvasive alternative to the Wada test, appropriate for clinical bedside evaluation.     

Fluid-attenuated inversion recovery MR imaging and subarachnoid hemorrhage: not a panacea

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) constitutes an important neurologic emergency. Some authors have suggested that fluid-attenuated inversion recovery (FLAIR) MR imaging can detect SAH that may not be apparent on CT scans but may be revealed by lumbar puncture. We sought to determine how often FLAIR MR imaging findings are positive for SAH in cases with negative CT findings and positive lumbar puncture results. METHODS: The CT scans and FLAIR MR images of all patients with suspected SAH during a 3-year interval (2000-2002) were retrospectively reviewed by a blinded reader. Among these cases, we identified 12 with CT findings that were negative for SAH, lumbar puncture results that were positive for SAH, and FLAIR MR imaging findings that were available for review. Eleven of the 12 patients had undergone FLAIR MR imaging within 2 days of CT and lumbar puncture. The 12 patients with negative CT findings were comprised of six male and six female patients with an age range of 7 to 69 years. We evaluated the true and false negative and positive FLAIR MR imaging findings for SAH by using the lumbar puncture results as the gold standard. The FLAIR MR imaging findings of 12 additional patients without SAH (as revealed by lumbar puncture) were used as control data for a blinded reading. RESULTS: For all 12 control cases without SAH, the FLAIR MR imaging findings were interpreted correctly. Of the 12 cases that had positive lumbar puncture results but false-negative CT findings for SAH, FLAIR MR imaging findings were true-positive in only two cases and were false-negative in 10. One of the two true-positive cases had the highest concentration of RBC in the series (365 k/cc), and the other had the second highest value of RBC (65 k/cc). CONCLUSION: FLAIR MR imaging cannot replace lumbar puncture to detect the presence of SAH. FLAIR MR imaging findings are infrequently positive (16.7%) when CT findings are negative for SAH. This is likely because there is a minimum concentration of RBC/cc that must be exceeded for CSF to become hyperintense on FLAIR MR images.