Hyperreninemia characterizing women with polycystic ovary syndrome improves after metformin therapy

Background: Polycystic ovary syndrome (PCOS) is characterized by chronic anovulation, hyperandrogenemia and insulin resistance. Hyperreninemia is observed in insulin resistance and hyperandrogenemic states. Aims: To investigate the levels of total plasma renin and their possible relationship with insulin resistance and hyperandrogenemia and to explore the effect of metformin on these parameters in PCOS women. Methods: 48 PCOS women who were age- and body mass index (BMI)-matched with 21 healthy women were studied. Total renin, aldosterone levels, glucose and insulin levels were measured at basal state and during an oral glucose tolerance test in all subjects. A subgroup of women with PCOS was evaluated 6 months after metformin administration. Results: Total renin levels were significantly higher in PCOS women compared to controls. PCOS women compared to controls displayed higher areas under the curve for glucose, insulin and total renin (AUCREN). Mean AUCREN was correlated significantly with insulin resistance indices and positively with free testosterone levels. Total renin, aldosterone, androgen levels and insulin sensitivity indices were significantly improved after 6 months on metformin treatment. Conclusions: PCOS women demonstrated an insulin resistance and hyperandogenemia-related increase in serum total renin levels. Metformin treatment was shown to significantly reduce total renin levels. Copyright © 2009 S. Karger AG

Early defects of GABAergic synapses in the brain stem of a MeCP2 mouse model of Rett syndrome

Rett syndrome is a neurodevelopmental disorder caused by mutations in the transcriptional repressor methyl-CpG-binding protein 2 (MeCP2) and represents the leading genetic cause for mental retardation in girls. MeCP2-mutant mice have been generated to study the molecular mechanisms of the disease. It was suggested that an imbalance between excitatory and inhibitory neurotransmission is responsible for the behavioral abnormalities, although it remained largely unclear which synaptic components are affected and how cellular impairments relate to the time course of the disease. Here, we report that MeCP2 KO mice present an imbalance between inhibitory and excitatory synaptic transmission in the ventrolateral medulla already at postnatal day 7. Focusing on the inhibitory synaptic transmission we show that GABAergic, but not glycinergic, synaptic transmission is strongly depressed in MeCP2 KO mice. These alterations are presumably due to both decreased presynaptic gamma-aminobutyric acid (GABA) release with reduced levels of the vesicular inhibitory transmitter transporter and reduced levels of postsynaptic GABA(A)-receptor subunits alpha2 and alpha4. Our data indicate that in the MeCP2 -/y mice specific synaptic molecules and signaling pathways are impaired in the brain stem during early postnatal development. These observations mandate the search for more refined diagnostic tools and may provide a rationale for the timing of future therapeutic interventions in Rett patients

Impact of dietary modification of advanced glycation end products (AGEs) on the hormonal and metabolic profile of women with polycystic ovary syndrome (PCOS)

Objective: To investigate the impact of dietary intervention on Advanced Glycation End products (AGEs) intake on the hormonal and metabolic profile in women with polycystic ovary syndrome (PCOS). Methods: After baseline evaluation, 23 women with PCOS [mean±SD, age: 23.4±5.7 years; body mass index (BMI): 26±5.7 kg/m2] underwent the following consecutive 2-month dietary regimens: a hypocaloric diet with ad-libitum AGEs content (Hypo), an isocaloric diet with high AGEs (HA) and an isocaloric diet with low AGEs (LA). Metabolic, hormonal and oxidative stress status was assessed and AGEs levels were determined in all subjects after the completion of each dietary intervention. Results: Serum levels of AGEs, testosterone, oxidative stress, insulin and HOMA-IR index were significantly increased on the HA compared to the Hypo diet and subsequently decreased on the LA diet (compared to HA) (p<0.05 for all parameters). BMI remained unaltered throughout the HA and LA periods compared to the Hypo period. Serum AGEs were strongly correlated with insulin, as well as with HOMA, during the LA dietary period (r=0.53, p=0.02 and r=0.51, p=0.03, respectively). For the same period, dietary AGEs were correlated with insulin levels (rho=0.49, p=0.04). Conclusions: Modifications of dietary AGEs intake are associated with parallel changes in serum AGEs, metabolic, hormonal and oxidative stress biomarkers in women with PCOS. These novel findings support recommendations for a low AGEs dietary content along with lifestyle changes in women with PCOS

Brown tumor of the fibula: unusual presentation of an uncommon manifestation. Report of a case and review of the literature

Brown tumors are erosive bony lesions caused by rapid osteoclastic activity and peritrabecular fibrosis due to hyperparathyroidism, resulting in a local destructive phenomenon. Although brown tumors are the most pathognomonic sign of hyperparathyroidism, they are very rarely observed at present as a result of early detection of hypercalcemia and elevated parathyroid hormone levels. The rare appearance of this entity in everyday practice is troublesome for both patients and physicians, because whenever it emerges, diagnosis could be mistaken for a giant cell tumor of the bone. However, clinical, biochemical, and radiologic findings can easily guide the diagnosis if one considers the full continuum of findings and their association with subject’s medical history, instead of focusing only on bone lesion. In this report we present a case of brown tumor in the fibula with a short literature review, whose aggressive presentation and unawareness of the skeletal findings of hyperparathyroidism puzzled the caring doctors. This case illustrates the need for continuous vigilance of any physician, regardless of his specialty or his position in medical services structures

“Menstrual Irregularities in PCOS. Does it Matter when it Starts?”

Background: PCOS is presented by a broad spectrum of menstrual irregularities appearing often at puberty or later on during the reproductive years in women suffering from this multifaceted syndrome. To our knowledge, there is no evidence to suggest whether the time of onset of menstrual irregularities (peri or post pubertal) indicates a differential metabolic and/or hormonal profile as well as ovarian ultrasonographic findings, in adulthood in women with PCOS. Aim of the study: To compare anthropometric, hormonal-metabolic profile and ultrasound findings in PCOS women with peripubertal onset of menstrual disorders with the corresponding data obtained from PCOS patients with post pubertal onset of menstrual irregularities, matched for BMI and age. Patients-Methods: 89 PCOS women were evaluated cross-sectionally at the age of 25 years. In 49 subjects menstrual irregularities were present from menarche, whereas in 40 women the irregularities appeared at least 3 years post menarche. Results: Anthropometric parameters were comparable between the 2 groups. The 2 groups did not differ on metabolic and hormonal profile as well as ovarian ultrasound findings. Conclusions: These data indicate that the timing of menstrual irregularities, do not appear to have an impact, on hormonal/metabolic profile and ovarian ultrasound morphology in patients diagnosed with PCOS, later in life