Cigarette smoke condensate-induced oxidative DNA damage and its removal in human cervical cancer cells

Exposure to cigarette smoke is well documented to increase oxidative stress and could account for higher risk of cervical cancer in smokers. Cervical pre-cancerous lesions that are initiated by human papillomavirus (HPV) infection generally regress in the absence of known risk factors such as smoking. 8-oxodeoxyguanosine (8-oxodG) is a highly mutagenic oxidative DNA lesion that is formed by the oxidation of deoxyguanosine. In the present study, we examined: a) the effect of cigarette smoke condensate (CSC) on 8-oxodG formation in and its removal from HPV-transfected (ECT1/E6 E7), HPV-positive (CaSki) and HPV-negative (C33A) human cervical cancer cells, and b) the cell cycle progression and apoptosis in CSC-treated ECT1/E6 E7 cells. CSC induced 8-oxodG in a dose- (p=0.03) and time (p=0.002)-dependent fashion in ECT1/E6 E7 cells as determined by flow cytometry. A 2.4-fold higher level of 8-oxodG was observed in HPV-positive compared with HPV-negative cells. However, 8-oxodG lesions were almost completely removed 72 h post-exposure in all cell lines as determined by ImageStream analysis. This observation correlates with the 2- and 5-fold increase in the p53 levels in ECT1/E6 E7 and CaSki cells with no significant change in C33A cells. We conclude that: a) cigarette smoke constituents induce oxidative stress with higher burden in HPV-positive cervical cancer cells and b) the significant increase observed in p53 levels in wild-type cervical cells (ECT1/E6 E7 and CaSki) may be attributed to the p53-dependent DNA repair pathway while a p53-independent pathway in C33A cells cannot be ruled out.     

Changes in pro-oxidant-antioxidant balance after bare metal and drug eluting stent implantation in patients with stable coronary disease

ObjectivesIn this study we aimed to assess the changes in pro-oxidant–antioxidant balance (PAB) after the placement of either a drug-eluting-stent (DES) or bare-metal-stent (BMS) in patients with stable coronary artery disease.Design and methodsPercutaneous coronary interventions (PCI) with either BMS or DES were undertaken for 152 patients (82 in the BMS and 70 in the DES groups respectively). PAB values were measured 24 h before and after PCI.ResultsBaseline PAB values were 80.68 (64.98–99.37) and 98.86 (64.70–140.62) for BMS and DES group, respectively, which were not significantly different between the 2 groups (P > 0.05). Following PCI, median PAB values decreased to 72.10 (61.40–96.13) and 81.40 (54.15–121.90) in BMS and DES groups, respectively. The reduction was significant in both BMS and DES groups (P < 0.05). The changes in PAB values were ?2.81 (?12.76 to 2.31) for BMS and ?2.82 (?29.88 to 8.93) for DES group, which were not significantly different between the 2 groups (P > 0.05).ConclusionWe found that the reported difference in clinical outcomes following DES or BMS implantation cannot be attributed to differences in early changes in oxidative stress induction as assessed by changes in PAB values.     

Surgeons and Surgery from Ancient Persia (5,000 Years of Surgical History)

The development of surgery is indebted to scientists and surgeons from various civilizations throughout history. The present study considers surgery in the ancient Persian civilization. It highlights aspects of the subject, such as findings of the first trephinated skulls in Iran; surgeons’ social class (kareto baē?aza in the Avestan language—dating back 3,000 years); surgical operations such as cesarean section and procedures to treat breast cancer; and the use of anesthetic compounds and surgical practice in the military. It is hoped that this catalogue of historical evidence of surgical practice in ancient Persian civilization will contribute to the history of surgery, as an important field in medical science.     

High frequency of mutations in the PIK3CA gene helical and kinase coding regions in a group of Iranian patients with high-grade glioblastomas: five novel mutations

Glioblastoma multiform (GBM; World Health Organization (WHO) grade IV) and anaplastic astrocytomas (AA; WHO grade III) are highly aggressive and lethal astrocytic brain tumors. To detect cancer-specific somatic mutations in two hot-spot regions of PIK3CA gene, the helical and kinase domains (encoded by exons 9 and 20, respectively) in GBM and AA, the authors examined the respective sequences 31 paraffin-embedded samples (23 GBM and 8 AA). The samples were obtained from a group of Iranian patients affected with high-grade glioblastoma (HGG). The overall prevalence of PIK3CA mutations was 23% (7/31) for both tumor types (22% in GBM, and 25% in AA). Five mutations were detected in exon 20, p.Arg992Gln (c.2976G→A), p.Met1005Val (c.3014A→G), p.Ile1019→Val (c.3056A→G), p.Ser1008Cys (c.3024C→G), and p.Asn1044Asp (c.3130A→G), and one mutation in exon 9, p.Glu545Ala (c.1634A→C). Additionally exons 4-8 of P53 gene in four unrelated young patients, who showed no mutations in PIK3CA exons 9 and 20, were analyzed. Three mutations were identified: p.Pro72Ala (c.214C→G), g.11608G→T (homozygote splice mutation), and p.Thr170Thr (c.510G→A silent mutation). In conclusion, mutation detection in PIK3CA in patients with a high degree of malignancy and early age at diagnosis should be included in molecular diagnostic protocols, also with regard to possible upcoming therapies.     

Induction of MRSA Biofilm by Low-Dose β-Lactam Antibiotics: Specificity,Prevalence and Dose-Response Effects

Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital- and community-associated infections. The formation of adherent clusters of cells known as biofilms is an important virulence factor in MRSA pathogenesis. Previous studies showed that subminimal inhibitory (sub-MIC) concentrations of methicillin induce biofilm formation in the community-associated MRSA strain LAC. In this study we measured the ability sub-MIC concentrations of eight other β-lactam antibiotics and six non-β-lactam antibiotics to induce LAC biofilm. All eight β-lactam antibiotics, but none of the non-β-lactam antibiotics, induced LAC biofilm. The dose-response effects of the eight β-lactam antibiotics on LAC biofilm varied from biphasic and bimodal to near-linear. We also found that sub-MIC methicillin induced biofilm in 33 out of 39 additional MRSA clinical isolates, which also exhibited biphasic, bimodal and linear dose-response curves. The amount of biofilm formation induced by sub-MIC methicillin was inversely proportional to the susceptibility of each strain to methicillin. Our results demonstrate that induction of biofilm by sub-MIC antibiotics is a common phenotype among MRSA clinical strains and is specific for β-lactam antibiotics. These findings may have relevance to the use of β-lactam antibiotics in clinical and agricultural settings.     

Zinc Sulfate for Relief of Pruritus in Patients on Maintenance Hemodialysis

Pruritus is a common complaint in patients undergoing maintenance hemodialysis. The pathophysiology of pruritus in these patients is not well known, but the role of histamine release from mast cells has been reported. According to the inhibitory effects of zinc on histamine release and reported low levels of serum zinc in hemodialysis patients, we aimed to evaluate the effects of zinc sulfate for the relief of pruritus in these patients. This double‐blind, randomized, placebo‐controlled trial was conducted on 40 adults with end stage renal disease (ESRD) who were on maintenance hemodialysis in two university hospitals in Isfahan, Iran. Patients were randomized to receive either zinc sulfate (440 mg/day) or placebo for two consecutive months. Pruritus was assessed at baseline and then every two weeks using a numerical rating scale from 0 to 10 until one month after treatment. Drug side effects were also assessed along with pruritus. There were 40 patients with a mean age of 55.5 ± 15.2 (72.5% male) who completed the study. The two groups were similar in baseline characteristics. Pruritus was decreased in both groups after treatment but there was a significantly greater decrease in the zinc sulfate group compared with placebo (P = 0.018). Patient compliance was good and no severe side effects were observed. Zinc sulfate (440 mg/day) is more effective than placebo for the relief of pruritus in patients under maintenance hemodialysis. Further studies with larger sample size, longer treatment duration and follow‐up and with various dosages of zinc sulfate are recommended.     

K6P2W18O62 encapsulated into magnetic Fe3O4/MIL-101 (Cr) metal–organic framework: a novel magnetically recoverable nanoporous adsorbent for ultrafast treatment of aqueous organic pollutants solutions

In this study, a Wells–Dawson type K₆P₂W₁₈O₆₂ polyoxometalate was encapsulated into the magnetic Fe₃O₄/MIL-101 (Cr) metal–organic framework and applied as a new magnetically recoverable ternary adsorbent to remove organic dyes from aqueous solutions. The as-prepared ternary magnetically recyclable hybrid (denoted as P₂W₁₈O₆₂@Fe₃O₄/MIL-101 (Cr)) was characterized by FT-IR spectroscopy, powder X-ray diffraction (XRD), Raman spectroscopy, EDX, SEM, BET surface area, and magnetic measurements. The results showed the successful encapsulation of K₆P₂W₁₈O₆₂ (∼26.5 wt%) into the magnetic Fe₃O₄/MIL-101 (Cr) framework. The magnetic hybrid had a high specific surface area of 934.89 m² g⁻¹. The adsorption efficiency of this nanohybrid for the removal of methylene blue (MB), rhodamine B (RhB), and methyl orange (MO) from aqueous solutions was evaluated. The magnetic nanohybrid demonstrated the fast and selective adsorption of cationic dyes from mixed dye solutions. The adsorption rate and capacity of P₂W₁₈O₆₂@Fe₃O₄/MIL-101 (Cr) were increased as compared with MIL-101 (Cr), P₂W₁₈O₆₂, and Fe₃O₄/MIL-101 samples due to the increased electrostatic attraction. The effects of parameters such as the adsorbent dosage, temperature, dye concentration, and pH were investigated on the adsorption process. The adsorption kinetics was analyzed by the Freundlich, Langmuir, and Temkin isotherm models and pseudo-second-order and pseudo-first-order kinetics models, with the Langmuir isotherm and pseudo-second-order kinetic model found to be suitable to describe the equilibrium data. Also, the thermodynamic results of the nanohybrid indicated that the adsorption was an endothermic and spontaneous process. After the adsorption reaction, the magnetic nanohybrid could be easily separated and reused without any change in structure. Based on the results of this study, the nanohybrid was an efficient adsorbent for eliminating cationic dyes.

A Wells–Dawson-type K₆P₂W₁₈O₆₂ polyoxometalate was encapsulated into the magnetic Fe₃O₄/MIL-101 (Cr) metal–organic framework and applied as a new magnetically recoverable ternary adsorbent to remove organic dyes from aqueous solutions.     

Thrombosis and infection: a case of transient anti-cardiolipin antibody associated with pylephlebitis

Infections with Bacteroides species have been noted to occur in association with cases of thrombophlebitis. This association has led to the speculation that the microorganisms themselves may contribute to the pathogenesis of thrombus formation through elaborated enzymes, including heparinases, or by interactions between the clotting cascade and the unique structure of the Bacteroides lipopolysaccharide. Anti-phospholipid antibodies have been linked with hypercoagulable states and thrombus formation. Although a number of infections have been associated with the transient production of anti-cardiolipin antibodies, the effect the antibodies may have in contributing to thrombus formation is not well understood. The occurrence of Bacteroides species infection with transient anti-cardiolipin antibody has not been previously reported.     

Changes in negative beliefs following three brief programs for facilitating recovery after assault

Background: This study examines whether changes in negative beliefs about oneself, others, and the world occur as a result of early intervention aimed at preventing the development of chronic PTSD and further explores whether changes in negative beliefs during early intervention mediate long‐term changes in psychopathology and functioning. Methods: Ninety recent female assault survivors were randomized to 4‐week early intervention programs: brief cognitive behavioral intervention, weekly assessment, or supportive counseling (SC). Changes in negative beliefs were examined from preintervention to postintervention. Results: Negative beliefs improved across interventions, with somewhat less benefit reported by participants receiving SC. As expected, before intervention more severe negative beliefs were associated with higher initial trauma reactions and these negative beliefs generally improved from preintervention to postintervention. Moreover, for the brief cognitive–behavioral intervention, changes in perceptions of self and one's safety mediated longer‐term changes in trauma‐related symptoms. Conclusions: The present results highlight the potential importance of changes in negative beliefs in long‐term adjustment of recent assault survivors. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.