Endothelial nitric oxide synthase VNTR (intron 4 a/b) polymorphism association with type 2 diabetes and its chronic complications

Subject and aims

Endothelial derived nitric oxide (eNOS) is involved in several functions playing important role in development of type 2 diabetes and insulin resistance. The aim of this study was to examine the association between eNOS intron 4 VNTR polymorphism and type 2 diabetes in an Iranian population.

Methods

A total of 220 patients with type 2 diabetes and 96 healthy control subjects were recruited from the same area. Genotyping was performed using PCR.

Results

A significant difference was found in genotype frequencies of eNOS polymorphism between patients and controls (aa + ab vs. bb p = 0.02, OR 2.0 95% CI; 1.05-3.96). Also allele a frequency was significantly increased in patients with diabetes compared with controls (p = 0.007, OR 2.1 95% CI; 1.19-4.08). We found that in patients with diabetic neuropathy the frequency of ‘a’ allele was significantly increased compared to the controls p = 0.03, OR = 1.8 95% CI (1.00-3.7). Both genotype and allele frequencies were significantly different between patients who were complication free compared to the controls [aa + ab vs. bb p = 0.007, OR = 2.6 95% CI (1.2-5.8) and p = 0.001, OR = 2.8 95% CI (1.4-5.9)] respectively with the a allele conferring the risk.

Conclusion

The association between eNOS VNTR polymorphism and T2DM seems to be stronger in patients without diabetic complications indicating diverse effect of eNOS polymorphism on diabetes and diabetic microvascular complications.     

Larger hip circumference independently contributed to reduced metabolic risks in Tehranian adult women

BACKGROUND: It has been suggested that health professionals may discard measurement of hip circumference from public health screening efforts. Before discarding the hip circumference in epidemiological surveys, it is important to consider whether any important information is likely to be lost. OBJECTIVE: To evaluate the relationship between hip circumference and metabolic risk factors in an urban adult population of Tehranian women. DESIGN: In this population-based cross-sectional study, a representative sample of 5720 women aged 18-74 years, were included. Demographic data was collected; anthropometric indices and blood pressure were measured according to standard protocol. Hypertension was defined based on Joint National Committee VI (JNC VI). Biochemical analysis was conducted on fasting blood samples. Diabetes was defined as fasting plasma glucose (FPG) > or =126 mg/dl or 2-h plasma glucose (2hPG) > or =200 mg/dl. Lipid disorders and components of metabolic syndrome were considered based on Adult Treatment Panel III (ATP III). RESULTS: Mean age of women was 39.9+/-14.6 years. Mean body mass index, waist-to-hip ratio, waist and hip circumferences for subjects were 27.1+/-5.1 kg/m2, 0.83+/-0.08, 86.5+/-13.1 cm and 103.5+/-9.8 cm, respectively. Higher hip circumference was associated with lower levels of serum total- and LDL-cholesterol, serum triglyceride, fasting plasma glucose, 2-h plasma glucose, systolic and diastolic blood pressure. Subjects in the top quintile of hip circumference had higher values of serum HDL-cholesterol concentration compared to those in the lower category. After adjustment for potential confounding variables and anthropometric measures associated with higher hip circumference, a significant decreasing trend was observed for odds of having high LDL-cholesterol (odds ratios among quintiles: 1.00, 0.98, 0.97, 0.95, 0.84, respectively, P for trend=0.04), diabetes (1.00, 0.68, 0.58, 0.45, 0.42, P for trend=0.01), hypertension (1.00, 0.96, 0.82, 0.78, 0.70, P for trend 0.02), low serum HDL-cholesterol (1.00, 1.03, 0.86, 0.82, 0.56, P for trend=0.04), elevated blood pressure (1.00, 0.99, 0.82, 0.70, 0.61, P for trend=0.01) and abnormal glucose homeostasis (1.00, 0.69, 0.66, 0.54, 0.48, P for trend=0.01) among hip circumference quintile categories. Individuals in the upper category of hip circumference had lower odds of having hypercholestrolemia (0.86 vs. 1.00) and high serum triglyceride levels (0.74 vs. 1.00) compared to those in the lowest category. CONCLUSION: Hip circumference is independently and inversely associated with metabolic risk factors. This study underscores the importance of continuing to measure hip circumference in epidemiologic surveys in Tehranian adult women.     

A randomized trial of ceftriaxone versus trimethoprim-sulfamethoxazole to prevent ventriculoperitoneal shunt infection.

BACKGROUND AND PURPOSE: Shunt infection represents a particularly morbid condition, which can also result in mortality. In order to decrease the high morbidity and mortality rates, prevention is an essential step. The purpose of this study was to compare the prophylactic use of ceftriaxone and trimethoprim-sulfamethoxazole (SXT) for the prevention of ventriculoperitoneal (VP) shunt infection. METHODS: In this prospective, single-institution, randomized clinical trial, 107 children with hydrocephalus and an indication for shunting were randomly assigned to prophylaxis with ceftriaxone (n = 50) or SXT (55), each administered as a single dose during anesthesia and two divided doses postoperatively. Patients were followed up for at least one year. RESULTS: The mean age of patients was 15 months, and 85% were aged 6 months or younger. During the first postoperative year, meningitis occurred in 13.5% of patients receiving ceftriaxone and 14.5% of the SXT group, with no statistically significant difference between the groups. Younger age, presence of cerebrospinal fluid leakage and aqueductal stenosis as a cause of hydrocephalus showed significant correlation with meningitis occurrence on univariate analysis. However, only the latter 2 factors were associated with meningitis on multivariate analysis. The risk of shunt infection did not correlate with the gender of the patient, time of VP shunt surgery, or duration of hospitalization for shunting. CONCLUSION: Ceftriaxone and SXT showed similar efficacy in preventing shunt infection. Cerebrospinal fluid leakage before or after VP shunt placement and aqueductal stenosis were independent risk factors for meningitis after VP shunt.     

Fine‐needle aspiration (FNA) and pleural fluid cytology diagnosis of benign metastasizing pleomorphic adenoma of the parotid gland in the lung: A case report and review of literature

Lesions that contain abundant benign myoepithelial cells, including pleomorphic adenomas of salivary gland origin, may present a diagnostic challenge in fine‐needle aspiration (FNA) specimens. Benign metastasizing pleomorphic adenoma is a rare neoplasm, in which the benign appearing pleomorphic adenoma, without any histological evidence of malignancy, metastasizes to distant sites including lung. In the absence of clinical history of a pre‐existing myoepithelial neoplasm, the presence of myoepithelial cells in the lung or any other organs besides salivary glands may create diagnostic difficulty. Here we present the cytologic findings of such a metastatic tumor found in the lung FNA and pleural fluid specimens from a 64‐year‐old woman, with a history of local recurrent salivary gland pleomorphic adenomas, who presented with multiple bilateral pulmonary nodules and pleural effusion. The diagnosis of benign metastasizing pleomorphic adenoma was made based on clinical information and cytomorphology, and confirmed by immunocytochemistry. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.     

Genetics of breast cancer bone metastasis: a sequential multistep pattern

Bone metastasis accounts for the vast majority of breast cancer (BC) metastases, and is related to a high rate of morbidity and mortality. A number of seminal studies have uncovered gene expression signatures involved in BC development and bone metastasis; each of them points at a distinct step of the ‘invasion-metastasis cascade’. In this review, we provide most recently discovered functions of sets of genes that are selected from widely accepted gene signatures that are implicate in BC progression and bone metastasis. We propose a possible sequential pattern of gene expression that may lead a benign primary breast tumor to get aggressiveness and progress toward bone metastasis. A panel of genes which primarily deal with features like DNA replication, survival, proliferation, then, angiogenesis, migration, and invasion has been identified. TGF-β, FGF, NFκB, WNT, PI3K, and JAK-STAT signaling pathways, as the key pathways involved in breast cancer development and metastasis, are evidently regulated by several genes in all three signatures. Epithelial to mesenchymal transition that is also an important mechanism in cancer stem cell generation and metastasis is evidently regulated by these genes. This review provides a comprehensive insight regarding breast cancer bone metastasis that may lead to a better understanding of the disease and take step toward better treatments.     

Glycosaminoglycan entrapment by fibrin in engineered heart valve tissues

Tissue engineered heart valves (TEHVs) may provide a permanent solution to congenital heart valve disease by permitting somatic valve growth in the pediatric patient. However, to date, TEHV studies have focused primarily on collagen, the dominant component of valve extracellular matrix (ECM). Temporal decreases in other ECM components, such as the glycosaminoglycans (GAGs), generally decrease as cells produce more collagen under mechanically loaded states; nevertheless, GAGs represent a key component of the valve ECM, providing structural stability and hydration to the leaflets. In an effort to retain GAGs within the engineered constructs, here we investigated the utility of the protein fibrin in combination with a valve-like, cyclic flexure and steady flow (flex–flow) mechanical conditioning culture process using adult human periodontal ligament cells (PLCs). We found both fibrin and flex–flow mechanical components to be independently significant (p < 0.05), and hence important in influencing the DNA, GAG and collagen contents of the engineered tissues. In addition, the interaction of fibrin with flex–flow was found to be significant in the case of collagen; specifically, the combination of these environments promoted PLC collagen production resulting in a significant difference compared to dynamic and statically cultured specimens without fibrin. Histological examination revealed that the GAGs were retained by fibrin entrapment and adhesion, which were subsequently confirmed by additional experiments on native valve tissues. We conclude that fibrin in the flex–flow culture of engineered heart valve tissues: (i) augments PLC-derived collagen production; and (ii) enhances retention of GAGs within the developing ECM.     

The effects of histaminergic agents in the ventral hippocampus of rats in the plus-maze test of anxiety-like behaviours

It has been suggested that histamine have modulatory influence on anxiety-related behaviours both in animals and humans. Ventral hippocampus (VHC) may also be an important brain site in the modulation of fear or anxiety. In the present study, the effects of histaminergic agents on anxiety-related behaviours in the rats, using plus-maze test has been investigated. Intra-VHC administration of histamine (2.5, 5 and 7.5 microg/rat) decreased %OAT and %OAE but not locomotor activity, showing an anxiogenic response. Pretreatment of animals with either pyrilamine, a H1 receptor antagonist (10 microg/rat), or ranitidine, a H2 receptor antagonist (10 microg/rat) reverse anxiogenic response of histamine (2.5, 5 and 7.5 microg/rat). However, intra-VHC microinjection of higher doses of pyrilamine (40 microg/rat) or ranitidine (20 and 40 microg/rat) alone increased anxiety-like behaviours in rats. Our results showed that histamine may modulate anxiety-like behaviours via H1 and H2 receptors in the ventral hippocampus of the rats.