Polymorphisms in the aurora-A gene is not associated with lung cancer in the Turkish population

Lung cancer, a complex neoplasm of lung tissue, is influenced by several environmental and genetic factors which could be changed in each individual. Aurora-A gene is related to mitotic events such as: chromosome instability, cell cycle regulation, spindle formation, and kinetechore-microtubule connections. This centrosomic serine/threonine kinase provides a strong connection between mitotic errors and carcinogenesis. The genomic alterations such as single nucleotide polymorphisms (SNPs) can exist in molecular pathways of lung cancer. Therefore, we evaluated the role of genetic polymorphisms of Aurora-A gene in the lung cancer in the Turkish population. Genotypes of five Aurora-A polymorphisms (F31I, V57I, 6328G/A, P50L, and S104L) were determined in 102 healty controls and 102 new diagnosed lung cancer cases. All samples were genotyped with DNA sequence technique. There were not any genotype variations in P50L, S104L, and 6328G/A polymorphisms. The frequencies of both genotypes F31I and V57I in lung cancer patients were not significantly different from those in controls (p > 0.05). A multivariable logistic regression analysis including patient characteristics, such as age and gender, did not change the results.     

Systemic cytokine response in murine anthrax

Systemic pro-inflammatory cytokine release has been previously implicated as a major death-causing factor in anthrax, however, direct data have been absent. We determined the levels of IL-1 beta, IL-6 and TNF-alpha in serum of mice challenged with virulent (Ames) or attenuated (Sterne) strains of Bacillus anthracis. More than 10-fold increase in the IL-1beta levels was detected in Ames-challenged Balb/c mice, in contrast to more susceptible C57BL/6 mice, which showed no IL-1beta response. Balb/c mice have also responded with higher levels of IL-6. The A/J mice demonstrated IL-1beta and IL-6 systemic response to either Ames or Sterne strain of B. anthracis, whereas no increase in TNF-alpha was detected in any murine strain. We used RT-PCR for gene expression analyses in the liver which often is a major source of cytokines and one of the main targets in infectious diseases. A/J mice challenged with B. anthracis (Sterne) showed increased gene expression for Fas, FasL, Bax, IL-1 beta, TNF-alpha, TGF-beta, MIP-1alpha, KC and RANTES. These data favour the hypothesis that apoptotic cell death during anthrax infection causes chemokine-induced transmigration of inflammatory cells to vitally important organs such as liver. Administration of caspase inhibitors z-VAD-fmk and ac-YVAD-cmk improved survival in Sterne-challenged mice indicating a pathogenic role of apoptosis in anthrax.     

The effects of lycopene on hepatic ischemia/reperfusion injury in rats

There is a very little information about the protective effect of lycopene (LYC) against hepatic ischemia–reperfusion injury. The present study was designed to examine the possible protective effect of the strong antioxidant and anti-inflammatory agent, LYC, on hepatic ischemia/reperfusion injury. For this purpose, rats were subjected to 45 min of hepatic ischemia followed by 60 min of reperfusion period. LYC at the doses of 2.5 and 5 mg/kg body weight (bw) were injected intraperitoneally, 60 min prior to ischemia. Upon sacrification, hepatic tissue samples were used for the measurement of catalase (CAT) activity and malondialdehyde (MDA) levels. Also, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) were assayed in serum samples. As a result of the use of LYC at the doses of 2.5 and 5 mg/kg bw; while improvements of the ALT, AST, LDH and MDA values were partial and dose-dependent, the improvement of CAT activity was total and dose-independent (p < 0.05). Our findings suggest that LYC has a protective effect against ischemia/reperfusion injury on the liver.     

Molecular epidemiology of methicillin-resistant Staphylococcus aureus isolates from clinical specimens of patients with nosocomial infection: are there unnoticed silent outbreaks?

Bacteriological and epidemiological studies were carried out on 90 isolates of methicillin-resistant Staphylococcus aureus (MRSA) at Turgut Ozal Medical Center of In?nü University, (Malatya/Turkey). MRSA isolates were obtained from patients with nosocomial infections. Staphylococcus aureus clinical isolates were collected between May 2004-May 2005. Isolates were tested for resistance to methicillin. Antimicrobial susceptibility testing and slime production evaluation was performed. Genotype studies were carried out by arbitrarily primed polymerase chain reaction (AP-PCR) and consequent cluster analysis. All of the isolates were mecA-positive in a PCR-based assay; all exhibited resistance to oxacillin, by agar dilution (MICs > or = 4 mg/L) and disc diffusion methods, and multiple antibiotics. Most MRSA isolates were collected in intensive care units. Of 90 samples, 53 were found to be unrelated to the others while the remaining 37 strains were either identical or closely related. Dendrogram analysis identified nine major clusters. These data support the opinion that MRSA are significant nosocomial pathogens in intensive care units and that resistant clones may be transmitted between patients. Molecular epidemiological tools are helpful for understanding transmission patterns and sources of infection, and are useful for measuring outcomes of intervention strategies implemented to reduce nosocomial MRSA.     

The hepatoprotective effects of Hypericum perforatum L. on hepatic ischemia/reperfusion injury in rats

Little is known about the effective role of Hypericum perforatum on hepatic ischemia–reperfusion (I/R) injury in rats. Hence, albino rats were subjected to 45 min of hepatic ischemia followed by 60 min of reperfusion period. Hypericum perforatum extract (HPE) at the dose of 50 mg/kg body weight (HPE₅₀) was intraperitonally injected as a single dose, 15 min prior to ischemia. Rats were sacrificed at the end of reperfusion period and then, biochemical investigations were made in serum and liver tissue. Liver tissue homogenates were used for the measurement of malondialdehyde (MDA), catalase (CAT) and glutathione peroxidase (GPx) levels. At the same time alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were assayed in serum samples and compared statistically. While the ALT, AST, LDH activities and MDA levels were significantly increased, CAT and GPx activities significantly decreased in only I/R-induced control rats compared to normal control rats (p < 0.05). Treatment with HPE₅₀ significantly decreased the ALT, AST, LDH activities and MDA levels, and markedly increased activities of CAT and GPx in tissue homogenates compared to I/R-induced rats without treatment–control group (p < 0.05). In oxidative stress generated by hepatic ischemia–reperfusion, H. perforatum L. as an antioxidant agent contributes an alteration in the delicate balance between the scavenging capacity of antioxidant defence systems and free radicals in favour of the antioxidant defence systems in the body.     

P53 related apoptosis in kidneys in CO2 pneumoperitoneum rat model: an immunohistochemical study

Laparoscopic surgery techniques have been increasingly preferred to classic laparotomy by surgeons since 1987. However, this method may have some side effects on different intraabdominal organs including kidneys. The aim of this study is to evaluate the effects of different pressures of CO₂ on p53 related apoptosis in kidneys. Totally 24 male rats were divided into four equal groups. CO₂ is insufflated into rats’ intraabdominal cavity in two different pressures of 10 and 20 mmHg during 1 h. However, in sham group, only cannula was inserted, but no gas was insufflated. After 1 h, 30 min reperfusion was applied. At last, the kidneys were excised and p53 expression and apoptosis were evaluated immunohistochemically. All the data revealed that the number of apoptotic cell in kidney’ tubular cells significantly increases in proportion to CO₂ pressure level. On the other hand, p53 expression was detected only in the highest pressure. Because the low CO₂ pressured group’ rats had no p53 expression in kidneys, we suggest that this method can be safely used for abdominal surgery. At the same time, increasing in the number of apoptotic cells parallel to pressure also suggest that CO₂ pressure level and application time are very important parameters during CO₂ pneumoperitoneum.     

Oxidative and nitrative stress markers in glaucoma

Glaucoma is a progressive optic neuropathy and is the leading cause of blindness in the United States and other industrialized countries. Elevated pressure in the eye is a risk factor for glaucoma and indeed experimental studies of induced pressure elevation in nonhuman primate's results in typical glaucomatous optic nerve damage. However, normal intraocular pressure can also lead to loss of vision in glaucoma. Although the initiating causes leading to glaucoma are unknown, oxidative and nitrative stress appears to play a role in the progressive neuronal death that is characteristic of glaucomatous optic nerve damage. Increased markers of oxidative stress that have been reported in glaucoma include protein nitrotyrosine, carbonyls in proteins, lipid oxidation products and oxidized DNA bases. Studies have also highlighted the role of nitric oxide in glaucoma by reporting the presence of inducible nitric oxide synthase in the iris-ciliary body, retina and in the glaucomatous optic nerve head of experimental rat models. This review discusses the role of reactive oxygen and nitrogen species in the pathogenesis of glaucoma and examines the relevance of antioxidants in neurodegeneration associated with the disease. It is concluded that oxidative and nitrative stress have a pathogenic role in glaucoma.     

TMEM231, mutated in orofaciodigital and Meckel syndromes,organizes the ciliary transition zone

The Meckel syndrome (MKS) complex functions at the transition zone, located between the basal body and axoneme, to regulate the localization of ciliary membrane proteins. We investigated the role of Tmem231, a two-pass transmembrane protein, in MKS complex formation and function. Consistent with a role in transition zone function, mutation of mouse Tmem231 disrupts the localization of proteins including Arl13b and Inpp5e to cilia, resulting in phenotypes characteristic of MKS such as polydactyly and kidney cysts. Tmem231 and B9d1 are essential for each other and other complex components such as Mks1 to localize to the transition zone. As in mouse, the Caenorhabditis elegans orthologue of Tmem231 localizes to and controls transition zone formation and function, suggesting an evolutionarily conserved role for Tmem231. We identified TMEM231 mutations in orofaciodigital syndrome type 3 (OFD3) and MKS patients that compromise transition zone function. Thus, Tmem231 is critical for organizing the MKS complex and controlling ciliary composition, defects in which cause OFD3 and MKS.