Polycystic ovary syndrome (PCOS) is a heterogeneous condition which is related to an endocrine reproductive disorder of females. It affects females of 18–44 age. The persistent hormonal disbalance leads to the complexities such as numerous cysts, an irregular menstrual cycle that ultimately leads to infertility among females. Many candidate genes have been identified to be one of the causes of PCOS. Different studies have been carried out to find the genetic correlation of PCOS. It is essential to carry out such studies that identify the clear cause of PCOS and its genetic association and hormonal disbalance. This review has highlighted different genes and their correlation with PCOS that leads to hormonal disbalance. Yet not in-depth but an attempt to study the genetic predisposition of PCOS.

The present study deals with the diabetic neuropathies prevailing in the male population. In this investigation 100 insulin-dependent diabetes mellitus (IDDM) and 314 non-insulin-dependent diabetes mellitus (NIDDM) patients with and without an objective evidence of neuropathy, having an age span of 15 to 80 years and the duration of diabetes distributed over 1-33 years were included along with age-matched nondiabetic controls. The diabetic subjects were evaluated for semen analysis. Results of semen analysis showed a highly significant increase (p > .0005) in total sperm output and sperm concentration in both IDDM and NIDDM neuropathic diabetic men. On the other hand, sperm motility and semen volume were found to be about 30 and 60% less, respectively, in IDDM and NIDDM patients, where as sperm morphology and quality of sperm motility remained unaffected. A comparison between IDDM and NIDDM neuropathic and non-neuropathic diabetic groups further indicated a nonsignificant difference in the parameters of semen analysis, thus suggesting an endocrine basis for the sexual disturbances of diabetic neuropathy. A significant rise in total sperm output in both IDDM and NIDDM neuropathic diabetic patients and a significant decrease in semen volume in both types of diabetic patients thus suggests some kind of Leydig cell hyperplasia, which in turn may stimulate spermatogenesis and atonia of the bladder and urethra, resulting in retrograde ejaculation.

Diabetic neuropathies were studied in 100 insulin-dependent diabetes mellitus patients, 314 non-insulin-dependent diabetes mellitus patients with and without an objective evidence of neuropathy (age span, 15-80 years; duration of diabetes distributed over 1-33 years), and their age-matched nondiabetic controls. Serum and urinary levels of pituitary-gonadal hormones were evaluated in the diabetic subjects. There were striking results, i.e., a significantly low serum total and serum free (urinary) testosterone level (p < .0005) and a significantly high serum and urinary FSH and LH and serum prolactin level (p < .0005), specifically in the neuropathic diabetic patients, suggesting a series of pathological reactions in the smooth musculature of genital organs characterized by an increase in the interstitial thickness of seminiferous tubules, peritubular and intertubular fibrosis, and tubular sclerosis. Testicular necrosis, probably due to neuropathy, provided an additional aid to confirm these findings. A decrease in semen volume and sperm motility in the diabetic neuropathic patients further suggested the involvement of the entire smooth musculature of the reproductive tract, leading to atonia of the bladder and urethra. Such complications are purely neurogenic. The low serum and urinary testosterone levels and increased serum and urinary FSH and LH and serum prolactin levels in the diabetic men with neuropathy suggest gonadal disorder (hypogonadotropic hypogonadism), which may be due to testicular necrosis and thickening of seminiferous tubules, causing autonomic lesion.

Introduction: Diabetes mellitus (DM) has been a growing epidemic worldwide and poses a major socio-economic challenge. The leading cause of DM death is nephropathy due to end-stage renal disease (ESRD). This study aims to identify the possible association of I/D variants of the ACE gene and M268T (rs699) of the AGT gene of renin-angiotensinaldosterone system (RAAS). Materials and methods: Study subjects include 115 patients with DM, 110 with diabetic nephropathy (DN) and 110 controls. Fasting blood samples were collected for biochemical analyses and PCR amplification of specific regions of the ACE and AGT genes using primers. Results: The distribution of ACE (I/D) II 28.8%, ID 35.6% and DD 35.6% while in DN II 24.5%, ID 41% and DD 34.5%. The AGT (M268T) genotypes were distributed in DM as TT 30.4%, MT 66.9% and MM 2.6% while in DN subjects TT 56.4%, MT 42.7% and MM 0.9%. Conclusion: Significant differences were observed in the DD genotype and D allele of the ACE gene and the TT genotype and T allele of AGT genes between diabetic patients with and without nephropathy. The study may conclude that the D allele polymorphism in the ACE gene and the T allele polymorphism in AGT gene may be considered as genetic risk factors for the development of nephropathy in diabetes.

BackgroundOvarian cancer is the 5th most common cause of deaths in the women among gynecological tumors. There are many growing evidences that stress and other behavioral factors may affect cancer progression and patient survival. The purpose of this study is to determine the key role of matrix metalloproteinases (MMPs), and cytokines in the aggregation and progression of ovarian cancer.MethodologyStress variables (MDA, AGEs, AOPPs, NO), profile of antioxidants (SOD, Catalase, Vitamin E & A, GSH, GRx, GPx) and inflammatory biomarkers (MMP-9, MMP-2, MMP-11, IL-1α and TNF-α) were biochemically assessed from venous blood of fifty ovarian cancer patients and twenty healthy control subjects. The results of all parameters were analyzed statistically by independent sample t-test.ResultsThe results of the study demonstrated that the levels of stress variables like MDA (3.38±1.12nmol/ml), AGEs (2.72±0.22 ng/ml), AOPPs (128.48±27.23 ng/ml) and NO (58.71±8.67 ng/ml) were increased in the patients of ovarian cancer as compared to control individuals whereas the profile of antioxidants like SOD, Catalase, Vitamin E, Vitamin A, GSH and GRx were decreased in ovarian cancer patients (0.11±0.08 μg/ml, 2.41±1.01μmol/mol of protein, 0.22±0.04 μg/ml, 45.84±9.07μg/ml, 4.88±1.18μg/ml, 5.33±1.26 μmol/ml respectively). But the level of GPx antioxidant was increased in ovarian cancer patients (6.58±0.21μmol/ml). Moreover the levels of MMP-9 (64.87±5.35 ng/ml), MMP-2 (75.87±18.82 ng/ml) and MMP-11 (63.58±8.48 ng/ml) were elevated in the patients. Similarly, the levels of various cytokines TNF-α and IL-1α were also increased in the patients of ovarian cancer (32.17±3.52 pg/ml and 7.04±0.85 pg/ml respectively).ConclusionMMPs are commonly expressed in ovarian cancer which are potential extrapolative biomarkers and have a major role in metastasis. Due to oxidative stress, different cytokines are released by tumor associated macrophages (TAMs) that result in the cancer progression. Consequently, tissue inhibitors of matrix metalloproteinases (TIMPs) are the valuable therapeutic approaches to complement conservative anticancer strategies.

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Background: The extracellular matrix protein 1 (ECM1) is a glycoprotein, expressed in skin and other tissues. Loss-of-function mutation in ECM1 causes a rare autosomal recessive disorder called lipoid proteinosis. Lipoid proteinosis is presented by varying degrees of skin scars, beaded papules along the eyelid margins, variable signs of hoarseness of voice and respiratory disorders. More than 250 cases of this disorder have been described in the literature, but occurrence of lipoid proteinosis in siblings is very rare. This study was designed to investigate the possible mutation causing lipoid proteinosis in a Pakistani family and to elaborate the scope of possible genetic changes, causing the genodermatosis in Pakistan.Main observations: In this study, two siblings (12 and 9-years sisters) were presented with scaly itchy lesions on whole body, hoarse voice and macroglossia. Their deceased father had similar clinical manifestations but mother and younger brother were unaffected. Blood samples from clinically affected and unaffected family members were collected with informed consent. The coding region of ECM1 gene containing 10 exons were amplified and sequenced.Both the affected siblings were shown to have homozygous frame shift mutation by deletion of the nucleotide T at 507, codon 169, exon 6. This resulted in a frame shift from codon 169 and appearance of a premature stop codon at 177, causing formation of a mutated protein (176 amino acids) instead of normal ECM1 protein (540 amino acids).Conclusion: A case of homozygous 62-bp insertion in ECM1 gene causing lipoid proteinosis has been reported in another Pakistani family. The current study presents a homozygous frame shift mutation supporting an unusual function of ECM1 protein and broadens the spectrum of disease-linked mutations in this rare case of genodermatosis in this region.

The present study deals with the diabetic neuropathies prevailing in men. In this investigation 100 insulin-dependent diabetes mellitus (IDDM) and 3 14 non-insulin-dependent diabetes mellitus (NIDDM) patients with and without an objective evidence of neuropathy, having an age span in between 15 and 60 years and a duration of diabetes distributed over 1-33 years, were included along with their agematched nondiabetic controls. The diabetic subjects were evaluated for the induction of erectile responses. Investigation of induction of erectile responses to erotic stimulation by film and fantasy revealed striking results in diabetic patients with established neuropathy. Both IDDM and NIDDM patients with neuropathy exhibited a highly significant decrease (P < .0005) in penile diameter and length, penile arterial pulse amplitude, both systolic and diastolic blood pressures, and heart rate compared to controls of the same age group. However, both IDDM and NIDDM patients without neuropathy showed a nonsignificant difference in the above-mentioned parameters compared to control subjects. A nonsignificant association of induction of erectile responses to erotic stimulations among IDDM and NIDDM patients with and without neuropathy was also observed, suggesting that impotence and altered erectile responses are likely to be associated with an increased frequency to autonomic neuropathy in these patients irrespective of their type of diabetes.