Israel Medical Association Journal

Background: Vulvar and vaginal malignant and premalignant lesions are uncommon and are clinically heterogeneous diseases with two pathways of carcinogenesis: human papillomavirus (HPV) induced or non-HPV induced.                    

Objectives: To evaluate the demographic and clinical characteristics associated with vulvar or vaginal cancer and vulvar and vaginal intraepithelial neoplasia 3 (VIN3, VAIN3).

Methods: We conducted a retrospective chart review of 148 women with vulvar and vaginal malignancy and pre-malignancy for the period October 2004 to October 2012, and identified 59 and 19 patients with vulvar and vaginal cancer respectively, and 57 and 13 patients with VIN3 and VAIN3 respectively

Results: The median age of vulvar cancer patients was 30 years older than that of VIN3 patients. HPV was found in 60% and 66.6% of vulvar and vaginal cancer patients respectively, and in 82.3% and 84.6% of patients with VIN3 and VAIN3 respectively. A history of cervical intraepithelial neoplasia (CIN) or warts was observed in 10% and 10.5% of vulvar and vaginal cancer patients respectively, and in 57.9% and 46% of patients with VIN3 and VAIN3 respectively. In 52.6% of patients the vaginal cancer was metastases from other organs. 

Conclusions: Most women with vulvar carcinoma are older than 70 years old. VIN3 and VAIN3 are associated with HPV infection and the most prevalent type is HPV16. Almost half the vaginal cancers are associated with metastases from other organs and almost half of VAIN3 is associated with past cervical dysplasia or carcinoma. 

 

Objectives: To evaluate the effect of vitamin D analogues on cardiac function and fibrosis in an animal model of cardiorenal syndrome.

Methods: Unilateral nephrectomy was performed and myocardial infarction induced in rats. Rats were treated with vitamin D receptor activator (VDRA, paricalcitol, 40 ng/250 g x 3/week) versus a vehicle. A third group of animals, which served as the control, underwent sham surgery and received no treatment. After 4 weeks of treatment, cardiac function and fibrosis were assessed by trans-thoracic echo and histology, respectively. As a parameter of systemic inflammation, previously shown to be altered in acute coronary syndrome, T regulatory (Treg) cell levels were measured by flow cytometry. Renal dysfunction was documented by standard laboratory tests.

Results: After 4 weeks of treatment, no significant improvement in cardiac function parameters was noted following VDRA administration. VDRA treatment did not significantly alter Treg cell systemic levels. Consistently, despite a trend toward less extent of myocardial fibrosis, we found no clear beneficial effects of VDRA on myocardial tissue inflammation and remodeling.

Conclusions: Vitamin D treatment showed no beneficial effects on cardiac function parameters and fibrosis in an animal model of cardiorenal syndrome. 

Background: Atherosclerosis is a well-established inflammatory disease in which T helper 1 (Th1) cells play a key role. Regulatory T (Treg) cells drive a shift from Th1 to Th2 response and were shown to be reduced in atherosclerosis. ST2/interleukin (IL)-33 signal was found to promote Th2 response, attenuating atherosclerotic plaque progression.

Objectives: To evaluated the effect of IL-33 on Treg cell number.

Methods: We employed flow cytometry to determine Treg cell number, as well as ST2 levels, among splenocytes of C57BL/6J vs ApoE-/- mice. Soluble ST2 (sST2) levels were detected by enzyme-linked immunosorbent assay. 

Results: IL-33 contributed to an increase in Treg cells, but this association was attenuated in ApoE knockout (ApoE-/-) atherosclerotic mice. As a possible mechanism we demonstrated a reduction in the levels of CD4+ST2+ cells by flow cytometry, which is cotemporary to the previously described decrease in Treg cells in ApoE-/- mice. Additionally, the serum level of the soluble ST2 (sST2) decoy receptor was higher in ApoE-/- mice than in control animals.

Conclusions: Our results suggest that a repressed ST2/IL-33 signaling may contribute to the decrease in Treg cells observed in atherosclerosis.