The effect of doxorubicin on rats that received toxic and carcinogenic benzo(a)pyrene.

Benzo(a)pyrene (B(a)P) is a polycyclic aromatic hydrocarbon with carcinogenic and toxic effects. Doxorubicin is a DNA-interacting drug widely used in chemotherapy. In the present study we investigated the effects of doxorubicin on rats that received benzo(a)pyrene. Sprague-Dawley male rats, 3-4 months old, were divided into 5 groups (n=9 per group). Group 1 (controls) received normal saline intraperitoneally (i.p.) and intragastrically (i.g.), Group 2 (controls) similarly received corn oil i.p. and i.g., Group 3 received corn oil soluble benzo(a)pyrene (10mg/kg b.wt every 10 days for 40 days), Group 4 received doxorubicin (4 mg i.p. on 3 consecutive days), Group 5 received doxorubicin for 3 days (as in group 4) followed by benzo(a)pyrene as in group 3. After twenty-four hours urine samples were collected, heart blood, liver and kidney tissue samples were obtained. Biochemical data were evaluated on urine and blood; liver and kidney tissue samples were investigated histologically. Uric acid, urine creatinine, creatine clearance, urea nitrogen, serum creatinine values, serum glutamic oxaloacetic transaminase (SGOT, AST), serum glutamic pyruvic transaminase (SGPT, ALT), alkaline phosphatase (ALP, AP), superoxide dismutase (SOD), catalase (CAT) activities and malondialdehyde (MDA) levels were significantly different in the 3rd group compared with control groups. Most of the parameters group 5 were statistically similar to control values. Histological appearance of the liver and the kidney tissue samples supported the improvement in the 5th group. The result of our study indicated that liver and kidney functions impaired with benzo(a)pyrene may be partially restored by doxorubicin

Plasminogen activator inhibitor-1 and susceptibility to lung cancer: a population genetics perspective

Aim: The aim of this study was to investigate the polymorphism frequency of plasminogen activator inhibitor-1 (PAI-1) (rs1799889) 4G/5G in patients with lung cancer. Methods: In this study, 286 genomic DNAs (154 lung cancer patients + 132 subjects without lung cancer) were analyzed. Polymorphisms were determined by using the polymerase chain reaction (PCR) method, with 4G and 5G allele-specific primers. PCR products were assessed by a charge-coupled device camera and exposed to 2% agarose gel electrophoresis. Results: The frequencies of the PAI-1 gene 4G/5G genotypes were found to be 21% 4G/4G, 16% 4G/5G, and 62% 5G/5G in the control group and 31.4% 4G/4G, 30.8% 4G/5G, and 37.8% 5G/5G in the patient group. It was determined that the 5G/5G genotype frequency was high in patients in comparison with other genotypes. Conclusions: This study found a statistically significant difference between the groups with respect to genotype distribution. Consequently, we can say that the PAI-1 gene 4G/5G polymorphism is associated with lung cancer in Turkey.Artvin Coruh University: 2011.M80.02.0

Evaluación de la iluminación natural y de las protecciones solares en edificios de oficinas de la ciudad de S. M. de Tucumán

El trabajo muestra los resultados del estudio de la eficiencia de las protecciones solares y del comportamiento lumínico de aventanamientos en edificios de oficinas construidos en San Miguel de Tucumán. Se realizaron simulaciones con programas computacionales en 16 edificios. Así también se llevó a cabo la evaluación de las protecciones solares en 13 edificios, con el objeto de determinar la eficiencia de los mismos y su adecuación climática para localidad en estudio. Los resultados muestran que en la mayor parte de los locales de oficinas no se cumple con los valores mínimos de iluminación natural sobre el plano de trabajo requeridos para la tarea visual y que las protecciones solares no se comportan adecuadamente, produciendo deslumbramiento y un excesivo aporte de calor al ambiente, generando condiciones de inconfort y un incremento en los costos para el acondicionamiento artificial. Es así que el 61% de los edificios relevados no cuentan con protecciones solares en las ventanas y el tratamiento de sus frentes no difiere según sea la orientación de los mismos, con una elevada proporción de superficies vidriadas. Por otra parte, el 75% de los locales no cumplen con los valores de iluminación natural mínimos de normas, en el punto medio del local y el 94% en el punto más desfavorable.The work shows the results of the study of the efficiency of the solar protection and of the light behavior of windows in office buildings of San Miguel of Tucumán. In order to determining the light behavior of the windows, they were carried out simulations with software in 16 buildings. Likewise it was carried out the evaluation of the solar protection in 13 buildings, in order to determining the efficiency of them and their climatic adaptation for the town in study. The results show that in most of the offices it is not fulfilled the minimum values of natural illumination on the working plane, required for the visual tasks, and that the solar protection don't behave appropriately, producing dazzle and an excessive contribution of heat to the interior, generating conditions of lack of comfort and an increment in the energy costs.Asociación Argentina de Energías Renovables y Medio Ambiente (ASADES

Are the angiotensin-converting enzime gene and acticity risk factors for stroke? São fatores de risco para acidente vascular cerebral o gene e a atividade da enzima conversora de angiotensina ?

Stroke is a multifactorial disease in which genetic factors play an important role. This study was carried out to determine angiotensin-converting enzyme (ACE) gene polymorphism in Turkish acute stroke patients and to establish whether there is an association of angiotensin-converting enzyme gene I/D polymorphism with clinical parameters. In this study 185 patients and 50 controls were recruited. We have investigated the association among the allelic distribution of the insertion/deletion (I/D) polymorphism of the ACE gene identified by polymerase chain reaction. Distribution of ACE gene I/D genotypes and allele frequencies in patients were not significantly different from controls. D allele frequencies were 57.8% in patients versus 53.0% in controls and I allele 42.2% versus 47% respectively. History of hypertension, stroke, renal, heart and vessel diseases incidence and age, gender, systolic-diastolic blood pressures and creatinine levels were significantly high in patients. But these results and ACE activities had no significant differences among the ACE genotypes in patients and controls. Our results suggest that the ACE gene polymorphism is not associated with the pathogenesis of stroke in Turkish stroke patients.<br>O acidente vascular cerebral (AVC) é doença multifatorial em que fatores genéticos desempenham papel importante. Este estudo foi desenvolvido para verificar o polimorfismo do gene da enzima conversora da angiotensina (ECA) em pacientes turcos com AVC agudo e estabelecer se existe associação do gene I/D da ECA com parâmetros clínicos. O estudo foi realizado com 185 pacientes e 50 controles. A associação entre a distribuição alélica da inserção / deleção (I/D) do polimorfismo do gene da ECA foi estudada pela reação em cadeia da polimerase. A distribuição dos genótipos I/D do gene da ECA e suas freqüências não apresentaram significância estatística quando comparados os pacientes e controles. As freqüências dos alelos D foram 57,8% nos pacientes versus 53% nos controles e dos alelos I 42,2% versus 47% respectivamente. Antecedentes de hipertensão, AVC, doença renal, doenças cardíacas, idade, gênero, pressão arterial sistólica e diastólica e níveis de creatinina foram significantemente elevados no grupo dos pacientes. No entanto estes resultados quando comparados com a atividade e o polimorfismo do gene da ECA não apresentaram diferenças estatísticas entre o grupo de pacientes e controles. Nossos resultados sugerem que o polimorfismo do gene da ECA não é associado com a patogênese do AVC em paciente turcos

Association between I/D polymorphism in the ACE gene and sarcoidosis in Turkish patients

Sarcoidosis is a chronic inflammatory disease with a complex pathogenesis and unknown etiology characterized by noncaseating granulomas that invade the lungs, eyes, liver and other organs. Insertion (I)/deletion (D) polymorphism in the gene encoding the angiotensin-converting enzyme (ACE) has been studied to examine the genetic predisposition to sarcoidosis in different populations, but the results have been inconsistent and inconclusive. This study aimed to determine the frequencies of the genotypes and alleles of I/D polymorphism in the ACE gene in Turkish patients as a distinct ethnic group and to investigate whether such polymorphism is associated with predisposition to sarcoidosis. Genomic DNA samples obtained from 154 individuals (70 patients with sarcoidosis and 84 healthy controls) were used in the study. The DNA was amplified using polymerase chain reactions using allele-specific primers. The amplified products were analyzed by 2 % agarose gel electrophoresis followed by UV transillumination. The allele frequencies and genotype distribution of the groups were analyzed using the Chi square test. There were no significant differences between the controls and sarcoidosis cases with respect to genotype distribution (chi(2) = 4.202, p = 0.122) and allele frequencies (chi(2) = 1.358, p = 0.244). Our results suggest that I/D polymorphism in the ACE gene does not cause a genetic predisposition to sarcoidosis in Turkish patients

Common Variants rs3815188 and rs1043994 on Notch3 Gene Confer Susceptibility to Lung Cancer: A Hospital-Based Case-Control Study

The Notch signaling pathway is a mechanism that plays a role in the determination of cell fate during cell development. Signals between neighbor cells are amplified through the Notch receptors. Notch activity is related to general growth stages such as organogenesis and morphogenesis and has effects on cell differentiation, cell proliferation, and apoptosis. Lung cancer associated with degradation of proteins which regulate cellular activities such as cell growth, differentiation, proliferation and apoptosis or the loss of function of proteins due to mutations in the genes which that express these proteins. We aimed to determine the frequency of the Notch3 rs3815188 (C381T) and rs1043994 (G684A) polymorphisms and to investigate whether this gene is associated with genetic predisposition of development of lung cancer. In this study, DNA samples were extracted from the venous blood sample of 200 subjects (100 lung cancer patients and 100 controls). Notch3 rs3815188 (C381T) and rs1043994 (G684A) polymorphisms were determined using the restriction fragment length polymorphism method. A statistically significant difference was found between the patient and control groups for Notch 3 gene rs3815188 and rs1043994 polymorphisms when evaluated in terms of genotype (p = 0.002 and p < 0.001, respectively) and allele frequencies (p < 0.05). In conclusion, the rs3815188 variant and rs1043994 variant of the Notch3 gene is associated with lung cancer risk in patients of Turkish origin

The effects of p38 gene silencing on breast cancer cells

p38 mitogen-activated protein kinases (MAPK) are members of the MAPK family that are activated by inflammatory cytokines and a variety of environmental stresses. It mediates various biological processes. p38 MAPK activity play important roles in tumour progression. Excessive p38 expression is observed in invasive breast cancers. The aim of the present study was to investigate whether the p38 siRNA transfection of breast cancer cells is a putative preventive treatment for human breast cancer. p38 siRNA was used at a concentration of 15, 30, and 100 nM in human breast cancer cell lines (MCF-7) and normal fibroblast cell lines (NIH 3T3). After 48 and 72 h of transfection, the reduction in p38 expression was measured using quantitative real-time PCR. The activation of p38 signalling was measured by ELISA. XTT cell proliferation assay was performed to determine the effect of p38 silencing on MCF-7 and NIH 3T3 cell lines. The results demonstrated that approximately 96 % gene silencing occurred by the selected siRNA targeting p38 mRNA. The most effective silencing was observed at 72 h post-transfection using 30 nM p38 siRNA. The results of ELISA showed that the expression of p38 protein was inhibited by p38 siRNA at 30 nM siRNA and 100 nM at 72 h post transfection. XTT results showed that cells stimulated by 30 nM siRNA at 72 h post transfection were the lowest in proliferation. p38 siRNA can interfere with the expression of p38 at protein level in MCF-7 cells, result in inhibition of cell proliferation. p38 siRNA may be a critical regulator to promote the proliferation and protein expression in MCF-7 cells. In this study, we demonstrate that p38 silencing is a preventive maintenance for treating breast cancer

Preventive role of gallic acid on hepatic ischemia and reperfusion injury in rats

There is little information about the hepatoprotective effects of gallic acid against ischemia-reperfusion (I/R) damage. Animals were subjected to I/R. Gallic acid at doses of 50 and 100 mg/kg body weight (bw) were injected as a single dose prior to ischemia. 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 gallic acid at a dose of 100 mg/kg bw 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 with no treatment group (P < 0.05). In oxidative stress generated by hepatic ischemia-reperfusion, gallic acid contributes partially an alteration in the delicate balance between the scavenging capacity of antioxidant defense systems and free radicals in favour of the antioxidant defense systems in the body

Common variants of genes encoding TLR4 and TLR4 pathway members TIRAP and IRAK1 are effective on MCP1, IL6, IL1 beta, and TNF alpha levels in type 2 diabetes and insulin resistance

Objective and designType 2 diabetes is a pandemic disease characterized by hyperglycemia, ineffective insulin use, and insulin resistance and affecting 1 in 11 people worldwide. Inflammation-related insulin resistance is thought to play an important role in the etiology of the disease. TLR4 is the central receptor of the natural immune system and has an important role as a trigger of the inflammatory response. The IRAK1 and TIRAP are members of the TLR4 pathway and involved in the TLR4-mediated inflammatory response. Genetic variants in the TLR4 gene or in the IRAK1 and TIRAP genes may have an important role in the development of insulin resistance and type 2 diabetes by disrupting the inflammatory response. In this direction, we aimed to investigate the relationship among TLR4 and IRAK1, TIRAP gene variants, and type 2 diabetes and insulin resistance, and investigate how these variants affect inflammatory factors (TNF-alpha, IL-6, MCP-1, and IL-1 beta).Subjects and methodsIn our study, a total of seven variations on the genes of TLR4 (rs4986790, rs4986791), IRAK1 (rs1059703, rs3027898, rs7061789), and TIRAP (rs8177374, rs8177400) were genotyped by the MassARRAY((R)) Iplex GOLD SNP genotyping in 100 type 2 diabetic patients and 100 non-diabetic individual. The TLR4 rs4986790 and rs4986791 variation was confirmed by PCR-RFLP method also. The serum IL1-beta, IL6, MCP-1, and TNF-alpha levels were measured using enzyme-linked immunosorbent assay kits.Results and conclusionAs a result of our study, no correlation was found among TLR4, IRAK1, and TIRAP gene variants and the risk of type 2 diabetes and insulin resistance. However, TNF-alpha, IL-6, MCP-1, and IL-1 beta levels were also associated with diabetes and insulin resistance (p>0.05). Although the gene variants were not significant in type 2 diabetes and insulin resistance groups, IRAK1, TLR4, and TIRAP gene variants were found to be associated with TNF-alpha, IL-6, MCP-1, and IL-1 beta levels

The genetic variants of solute carrier family 11 member 2 gene and risk of developing type-2 diabetes

Type-2 diabetes (T2DM) is a metabolic disorder characterized by long-term insulin resistance, impaired insulin secretion from -cells, and loss of beta cell mass and function. Inflammation and oxidative stress play a key role in the development of diabetes and are associated with insulin resistance. Notably, recent studies have demonstrated an association between body iron stores, insulin resistance and T2DM. Free iron, a powerful pro-oxidant molecule, is involved in oxidative stress, lipid peroxidation and endothelial dysfunction via its ability to generate free radicals. Specifically, the accumulation of iron in beta cells triggers oxidative stress and DNA damage, which have been reported to be associated with -cell death and apoptosis. Solute carrier family-11 member-2 (SLC11A2) functions to transport ferrous iron and some divalent metal ions throughout the plasma membrane and across endosomal membranes. Functional polymorphisms in the SLC11A2 gene have been reported to cause excess storage of iron, resulting in iron overload. In this study, we evaluated the association between T2DM and SLC11A2 gene variants IVS4+44C/A, 1303C/A and 1254T/C by performing PCR-RFLP analysis on 100 T2DM patients and 100 healthy subjects. PCR products were digested with MnlI, MboI and SfanI restriction endonucleases and the products were then separated by 3% agarose gel electrophoresis. The genotype frequencies of the 1254T/C and 1303C/A SLC11A2 gene variants did not differ between healthy controls and T2DM patients (P>0.05). But, in recessive model (P=0.037) and homozygous CC genotype (P=0.030) for IVS4+44C/A showed significant correlation with T2DM risk. It is thought that presence of C allele of IVS4+44C/A plays pathological roles