Association of a 27-bp repeat polymorphism in intron 4 of endothelial constitutive nitric oxide synthase gene with hypertension in a Tunisian population

Objectives

Nitric oxide (NO) produced by endothelial nitric oxide synthase (eNOS) mediates endothelium-dependent vasodilatation and antithrombotic action. Controversial results regarding the association of eNOS gene (NOS3) polymorphisms with hypertension have been reported. In the present study, we examined a possible association between the 27-base pair (bp) repeat polymorphism in intron 4 of the NOS3 gene and hypertension in a sample of the Tunisian population.

Design and methods

A total of 295 Tunisian patients with hypertension and 395 healthy controls were included in the study. The NOS3 gene intron 4a4b variable number of tandem repeats polymorphism was analyzed by PCR.

Results

A significant differences in genotype distribution and allele frequency was observed between patients and controls. Patients with hypertension had a frequency of 6.4% for the 4a4a genotype, 32.7% for the 4a4b genotype and 60.9% for the 4b4b genotype. The controls had a frequency of only 2.3% for the 4a4a genotype, 28.4% for the 4a4b genotype and 69.4% for the 4b4b genotype (χ² = 11.81, p = 0.003). The hypertension patient group showed a significant higher frequency of the 4a allele compared to the controls (0.23 vs. 0.16; χ² = 8.61, p = 0.003). The odds ratio of hypertension for 4a vs 4b allele frequencies was statistically significant 1.66 [1.09-2.53] at 95% CI, p = 0.01 in males, whereas it was non-significant in females (1.23 [0.84-1.81], p = 0.26).

Conclusion

The present study showed a significant and independent association between the NOS34a4b gene polymorphism (presence of 4a allele) and hypertension in the Tunisian population.     

Involvement of insulin-like growth factor-insulin receptor signal pathway in the transgenic mouse model of medulloblastoma

A transgenic mouse model expressing Simian virus 40 T-antigen (SV40Tag) under the control of a tetracycline system was generated. In this model, a cerebellar tumor was developed after doxycycline hydrochloride treatment. Real time-polymerase chain reaction and immunohistochemistry results indicated that the SV40Tag gene was expressed in the tumor. Pathological analysis showed that the tumor belonged to medulloblastoma. Further molecular characterization of the tumor demonstrated that the insulin-like growth factor (IGF) signaling pathway was activated. We also found that the SV40Tag could bind and translocate insulin receptor substrate 1 into the nucleus in primary cultured tumor cells. The interaction between the IGF pathway and SV40Tag may contribute to the process of malignant transformation in medulloblastoma. This transgenic animal model provides an important tool for studies on the signal pathways involved in the preneoplastic process in medulloblastoma and could help to identify therapeutic targets for brain tumors. ( Cancer Sci 2008; 99: 234–240)     

Apolipoprotein E polymorphism in the Tunisian population: frequency and effect on lipid parameters

OBJECTIVES: We determined the frequencies of apolipoprotein E (apo E) gene alleles and examined the association between apo E polymorphism and lipid parameters in a sample of the Tunisian population. DESIGN AND METHODS: Apo E polymorphism was investigated using PCR, and plasma lipid parameters were measured in 122 men and 111 women aged 35 to 87 years. RESULTS: The allele frequencies were epsilon2: 7.3%, epsilon3: 84.6%, and epsilon4: 8.1%. Apo E polymorphism was associated with significant differences (P<0.001) in total cholesterol, apo B and LDL cholesterol in both men and women. epsilon2 carriers had the lowest mean total cholesterol, apo B and LDL-C concentrations, and subjects with the epsilon4 allele had the highest levels. Triglycerides levels increased with the epsilon4 allele, but this did not reach statistical significance. These results remained unchanged after adjustment for age, body mass index, sex, hypertension, diabetes and smoking. However, in obese subjects (BMI>30 kg/m2), TG concentrations were significantly lower in individuals homozygous for the epsilon3 allele compared to those with the alleles epsilon2 or epsilon4. CONCLUSION: In this sample of the Tunisian population, the distribution of apo E gene alleles is similar to that observed in Southern European populations with low prevalence of the epsilon4 allele. Variations in the apo E gene play a role in determining plasma lipid levels. These data also suggest that effects of apo E alleles on lipids levels are partly dependent on environmental variables such as BMI. These findings highlight the importance of the gene/environment interaction on the deleterious effect of obesity on cardiovascular risk factors.     

Signet ring cell carcinoma of the gallbladder in a 22-year-old man: a case report and review of the literature

Primary carcinoma of the gallbladder is an uncommon malignancy with a variable incidence among different geographic locales and ethnic groups. Women are affected generally 3 times as often as men. Choleliths are a significant risk factor. Other risk factors include abnormal union of the choledochopancreatic ducts, obesity, multiparity, chronic infection with certain bacteria, and genetics. The signet ring cell subtype of adenocarcinoma is a rare entity. The behavior of this subtype is not well described in the literature. The authors present a case of signet ring cell carcinoma of the gallbladder, unusual in their case because of the patient's young age, male gender, African American ethnicity, and lack of choleliths or any other risk factors. They review the literature in English to characterize this rare subtype.     

Recommendations for the surgical treatment of endometriosis—part 1: ovarian endometrioma

Study question

What does this document on the surgical treatment of endometriosis jointly prepared by the European Society for Gynaecological Endoscopy (ESGE), ESHRE, and the World Endometriosis Society (WES) provide?

Summary answer

This document provides recommendations covering technical aspects of different methods of surgery for endometriomas in women of reproductive age.

What is already known

Endometriomas (ovarian endometriotic cysts) are a commonly diagnosed form of endometriosis, owing to the relative ease and accuracy of ultrasound diagnosis. They frequently present a clinical dilemma as to whether and how to treat them when found during imaging or incidentally during surgery. Previously published guidelines have provided recommendations based on the best available evidence, but without technical details on the management of endometriosis.

Study design, size and duration

A working group of ESGE, ESHRE and WES collaborated on writing recommendations on the practical aspects of endometrioma surgery.

Participants/materials, setting and methods

This document focused on endometrioma surgery. Further documents in this series will provide recommendations for surgery of deep and peritoneal endometriosis.

Main results and the role of chance

The document presents general recommendations for surgery of endometrioma and specific recommendations for cystectomy, ablation by laser or by plasma energy, electrocoagulation and a combination of these techniques applied together or with an interval between them.

Limitations and reasons for caution

Owing to the limited evidence available, recommendations are mostly based on clinical expertise.

Wider implications of the findings

These recommendations complement previous guidelines on the management of endometriosis.

Study funding/competing interests

The meetings of the working group were funded by ESGE, ESHRE and WES. CB declares to be a member of the independent data monitoring committee for a clinical study by ObsEva and receiving research grants from Bayer, Roche Diagnostics, MDNA Life Sciences and Volition. ES received honoraria for provision of training to healthcare professionals from Ethicon, Olympus and Gedeon Richter. The other authors declare that they have no conflict of interest.

     

Lymphoid tyrosine phosphatase R620W variant and inflammatory bowel disease in Tunisia

AIM:To assess the possible association between PTPN22(R620W) gene polymorphism and inflammatory bowel disease(IBD).METHODS:One hundred and sixty-four patients with IBD 105 Crohn‘s disease(CD) and 59 ulcerative colitis(UC) and 100 healthy controls were recruited.Genotyping of the PTPN22 gene 1858C→T polymorphism was performed by restriction fragment length polymorphism-polymerase chain reaction with Rsa Ⅰ digestion.RESULTS:The genotypic and allelic frequencies of(R620W) PTPN22 gene polymorphism reveal a sign...     

Parathyroid Hormone and Physical Exercise: a Brief Review

Parathyroid hormone (PTH) is the major hormone regulating calcium metabolism and is involved in both catabolic and anabolic actions on bone. Intermittent PTH exposure can stimulate bone formation and bone mass when PTH has been injected. In contrast, continuous infusion of PTH stimulates bone resorption. PTH concentration may be affected by physical exercise and our review was designed to investigate this relationship. The variation in PTH concentration appears to be influenced by both exercise duration and intensity. There probably exists a stimulation threshold of exercise to alter PTH. PTH regulation is also influenced by the initial bone mineral content, age, gender, training state, and other hormonal and metabolic factors (catecholamines, lactic acid and calcium concentrations).

Key Points

• Physical exercise can improve PTH secretion.
• Parathyroid hormone has both anabolic and catabolic effects on bone: intermittent treatment of PTH is anabolic whereas continuous treatment is catabolic.

Key words: Parathyroid hormone, physical exercise, calcium, catabolic/anabolic effects