Transforming Growth Factor ß1 (TGF-ß1) in the Sera of Postmenopausal Osteoporotic Females.

BACKGROUND: Postmenopausal osteoporosis is a major cause of morbidity in postmenopausal females. Transforming growth factor ß1 (TGF-ß1) and interleukin 18 (IL-18) play complex roles in normal bone metabolism, and in pathophysiology of postmenopausal osteoporosis. OBJECTIVES: The aim of this study was to design an analytic cross sectional study in order to further clarify the role of TGF-ß1 and IL-18 in osteoporosis of postmenopausal females. METHODS: A cross sectional study including 65 postmenopausal osteoporotic females as cases and 69 postmenopausal females of similar age without osteoporosis as controls was conducted. Dual energy X-ray absorptiometry (DXA) was used to determine bone mass density (BMD) of participants and T-scoring was applied to establish whether the patient has osteoporosis or not. Serum TGF-ß1 and IL-18 levels were measured by quantitative sandwich Enzyme linked immunosorbent assay (ELISA). RESULTS: Serum TGF-ß1 levels were significantly higher in osteoporotic postmenopausal females than non-osteoporotic individuals (23.8 vs. 15.8 ng/mL; P = 0.009). There was no difference between IL-18 levels in the sera of osteoporotic and non-osteoporotic postmenopausal females in this study. There was a positive correlation between body mass index (BMI) and serum level of TGF-ß1 (P = 0.04). CONCLUSIONS: Our study demonstrated that TGF-ß1 serum levels is higher in osteoporotic postmenopausal females than non-osteoporotic ones, and probably aberrant increase in TGF-ß1 in postmenopausal females can result in uncoupled bone resorption and formation, which leads to osteoporosis.

Association between Angiotensinogen M235T Polymorphism and Preeclampsia in Iranian Pregnant Women.

OBJECTIVE: To determine the possible association between the M235T variant of angiotensinogen gene and preeclampsia in Iranian preeclamtic women with hypertension during pregnancy. MATERIALS AND METHODS: During a case control study, we used polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis to investigate the association between M235T polymorphism in preeclamtic women compared to normotensive controls. RESULTS: The M235T polymorphism was significantly associated with increased preeclampsia risk in the studied population as supported by a p value of 0.017 and chi-square value of 8.12. The frequency of mutated allele and genotype distribution showed a significant difference between preeclamtic women and control groups. CONCLUSION: The result indicates that the AGT M235T polymorphism plays a significant role in preeclampsia observed in selected Iranian preeclamtic women, and it can be considered as a major risk factor for preeclampsia.

Comparing the effects of dietary flaxseed and omega-3 Fatty acids supplement on cyclical mastalgia in Iranian women: a randomized clinical trial.

Considering the negative side effects of chemical drugs, there is a great need for effective alternative treatment strategies to manage cyclical mastalgia. Therefore, this study aimed at comparing the effects of flaxseed diet and omega-3 fatty acids supplement on treatment of cyclical mastalgia. In this study, 61, 60, and 60 women, respectively, received flaxseed as bread, omega-3 fatty acids as pearl, and wheat bread as their diet for two menstrual cycles. At the baseline cycle and end of both interventional cycles, intensity of mastalgia was measured using visual analogue scale. Analysis of covariance showed a significant difference among the three groups regarding the mean intensity of cyclical mastalgia in the first and second cycles of the interventions (P < 0.001). Also, repeated measures analysis of covariance with adjustment of two variables of age and mastalgia intensity of the baseline cycle demonstrated that flaxseed bread was more effective compared to omega-3 and wheat bread (P < 0.001). The results of this study demonstrated that flaxseed bread diet was an effective approach in decreasing cyclical mastalgia and could be prescribed to women as a simple treatment with few complications.

FoxP3+ regulatory T cells in peripheral blood of patients with epithelial ovarian cancer.

BACKGROUND: Ovarian cancer is the fifth leading cause of death from malignancy in women. CD4+CD25+FoxP3+ regulatory T (Treg) cells are a subset of T lymphocytes with great inhibitory impact on immune response. OBJECTIVES: To investigate the percentage of CD4+CD25+FoxP3+ regulatory T cells in the peripheral blood of the Iranian patients with epithelial ovarian cancer compared to healthy women and to evaluate the correlation of the Treg cell percentage with clinicopathological characteristics including cancer stage and CA-125 serum level. METHODS: Seventeen women with epithelial ovarian cancer and 20 healthy subjects were enrolled in the study. Peripheral blood mononuclear cells were stained at the surface, for CD4 and CD25 molecules, followed by fixation, permeabilization and intracellular staining for FoxP3 molecule. After processing and flowcytometry analysis, prevalence of Treg cells was determined as the percentages of CD25+FoxP3+ cells among CD4+ lymphocytes. RESULTS: Despite no difference in the percentage of total CD4+ lymphocytes, analysis indicated that Treg cell percentage was significantly higher in ovarian cancer patients than controls (5.7 ± 3.1% versus 2.8 ± 1.4%, p=0.002). A trend toward higher Treg cells was observed in higher stages of ovarian cancer (III+IV) in comparison to lower stages (I+II) (6.5 ± 3.2% vs. 4.44 ± 2.7%, p=0.2). Higher percentage of Treg cells was also observed in the patients with high CA125 (CA-125 >100 U/mL) in comparison to those with low CA-125 serum level (CA-125 ≤ 100 U/mL) although the difference was not significant (6.44 versus 4.18%, p=0.19). CONCLUSION: Increased frequency of Tregs in ovarian cancer might participate in immune suppression in these patients. The findings collectively suggest the likely impact of Treg cell-targeted immunotherapy in ovarian cancer.

Serum Levels of Anti-histone and Anti-double-Strand DNA Antibodies Before and After Laparoscopic Ovarian Drilling in Women with Polycystic Ovarian Syndrome.

OBJECTIVES: To determine the serum levels of anti-dsDNA, anti-histone, and anti-nucleosome antibodies after laparoscopic ovarian electrocauterization in patients with polycystic ovarian syndrome (PCOS). METHODS: Our study was performed on 35 patients with PCOS resistant to medical therapy, 35 patients with unexplained infertility, and 35 healthy fertile individuals. Patients with PCOS underwent laparoscopic electrocauterization while those with unexplained infertility underwent diagnostic laparoscopy. Serum levels of anti-dsDNA, anti-histone, and anti-nucleosome antibodies were measured at baseline and 1 month after operation and were compared between groups. RESULT: Baseline characteristics were similar between groups. Patients with PCOS had significantly higher levels of anti-dsDNA compared to unexplained infertility (p < 0.001) and control groups (p = 0.001). Anti-histone antibodies were higher in PCOS group compared to control group (p = 0.001). In those patients suffering from PCOS, anti-histone antibody increased significantly 1 month after ovarian electrocauterization (p = 0.017). Similarly, serum levels of anti-nucleosome antibodies increased significantly 1 month after operation (p < 0.001). CONCLUSION: Laparoscopic ovarian electrocauterization in patients with PCOS results in increased levels of anti-histone and anti-nucleosome antibodies. Anti-dsDNA, anti-histone, and anti-nucleosome antibodies also increase after diagnostic laparoscopy in those with unexplained infertility. Patients with PCOS have higher levels of anti-dsDNA and anti-histone antibodies compared to those with unexplained infertility and healthy fertile subjects.

Anti-Nuclear Antibodies in Patients with Polycystic Ovary Syndrome before and after Laparoscopic Electrocauterization.

Polycystic ovary syndrome (PCOS) has been suggested to be linked with autoimmune processes. Laparoscopic ovarian electrocauterization has the potency to stimulate more autoimmune reactions in PCOS patients. In the present study, we considered anti-nuclear antibodies (ANAs) as the hallmark of autoimmune reactions, and investigated the serum level of these antibodies in 35 patients with PCOS (21-38 years old) pre and one-month after electrocauterization, and in 35 fertile healthy women (25-35 years old) as the control group. Serum levels of ANAs, as well as ANA subtyping, were investigated using the Enzyme-Linked Immunosorbent Assay (ELISA). While 3 out of the 35 patients (8.6%) were positive for ANAs before electrocauterization, none of the controls was positive. The number of ANA-positive cases increased following electrocauterization (3 out of 35 [8.6%] before vs. 10 out of 35 [28.6%] after the procedure). The main ANA subtype in the positive samples was SS-A. The higher ANA level among the PCOS patients suggests association of the disease with autoimmune reactions. Laparoscopic ovarian electrocauterization seems to increase the number of positive-ANA patients.

HER2 Ile655Val Single Nucleotide Polymorphism in Patients with Ovarian Cancer.

BACKGROUND: The association between HER2 Ile655Val single nucleotide polymorphism and cancer is controversial. OBJECTIVES: The aim of our study was to investigate this polymorphism in patients with ovarian cancer. PATIENTS AND METHODS: Genomic DNA was extracted from peripheral blood leukocytes of 107 patients and 130 healthy women. HER2 gene polymorphism was assessed by PCR-RFLP. RESULTS: No significant difference was observed in genotype and allele frequency between patient and control groups according to HER2 Ile655Val polymorphism. The disease stage, age, and histological type were also not associated with the polymorphism. CONCLUSIONS: Our data showed that HER2 Ile655Val single nucleotide polymorphism was not significantly associated with onset, histological type, age, and stage of ovarian cancer in Iranian patients.

Interleukin-18 gene promoter and serum level in women with ovarian cancer.

IL-18, initially defined as a potent inducer of IFN- gamma production, is a systemic, multifunctional cytokine with both pro-cancerous and anti-cancer activities. The contribution of the IL-18 promoter polymorphisms at positions -607 (C/A) and -137 (G/C) to cancer development has been reported. We sought to examine IL-18 serum level and its polymorphisms in Iranian women with ovarian cancer. Single nucleotide polymorphisms (SNPs) at positions -607 (C/A) and -137 (G/C) were analyzed by allele-specific polymerase chain reaction in 85 women with ovarian cancer and 158 healthy controls. IL-18 serum level was determined using ELISA method. No significant association was found between the allele, genotype, and haplotype distributions of the SNPs and ovarian cancer. Mean IL-18 serum level was significantly higher in patients than in controls (P = 0.008). Comparing IL-18 serum levels with genotypes at positions -607 and -137 revealed no significant difference. No association was also found between IL-18 levels and the disease stage. In conclusion, our results indicate that IL-18 promoter polymorphisms at positions -607 (C/A) and -137 (G/C) appear not to confer susceptibility to ovarian cancer in Iranian population; however, IL-18 serum level increases in ovarian cancer patients.

Effectiveness of leukocyte immunotherapy in primary recurrent spontaneous abortion (RSA).

BACKGROUND: Recurrent spontaneous abortion (RSA) is defined as three or more sequential abortions before the twentieth week of gestation. There are evidences to support an allo-immunologic mechanism for RSA. One of the methods for treatment of RSA is leukocyte therapy; however there is still controversy about effectiveness of this method. OBJECTIVES: To evaluate the effectiveness of leukocyte therapy for treatment of RSA. METHODS: Ninety two non-pregnant women with at least three sequential abortions (60 primary & 32 secondary aborters) recognized as RSA were referred to our Laboratory for immunotherapy. All the cases were immunized by isolated lymphocytes from their husbands. Fifty to 100 million washed and resuspended mononuclear cells were injected by I.V., S.C., and I.D. route. The result of each injection was checked by WBC cross matching between couples after four weeks of injections. Immunization was repeated in fifth week to a maximum of 3 times if needed. Eighty one age-matched non-pregnant RSA women (52 primary and 29 secondary aborters) with at least three sequential abortions were also included in this study as controls. The control group was not immunized. RESULTS: 67 out of 92 (72.8%) immunized cases and 44 out of 81 controls (54.3%) showed a successful outcome of pregnancy (p<0.02). Comparison of primary and secondary aborters indicated a significantly better outcome only in primary (75% vs. 42.3%. p<0.001) but not in secondary aborters (68.8% vs. 75.9%, p = 0.7). CONCLUSION: The present investigation showed the effectiveness of leukocyte therapy in primary but not in secondary RSA patients. Despite the current controversy and limitation of leukocyte therapy in RSA, the results of our investigation provide evidence supporting the use of allo-immunization in improving the outcome of pregnancy in primary RSA patients.