Role of diagnostic hysterolaparoscopy in the evaluation of infertility

Background: Infertility has become nowadays not only a medical, but a social problem as well. None of the laboratory findings alone is conclusive in diagnosing infertility. Diagnostic hysterolaparoscopy is an accurate method of assessing and treating infertility. Direct visualization of abdominal and pelvic organs in hysteroscopy and laparoscopy allows a definite diagnosis where clinical examination and less invasive techniques such as ultrasound, SSG and HSG fail to identify the problem. The main objective of study was to determine the role of diagnostic hysterolaparoscopy in the evaluation of infertility in tertiary care centers.Methods: A prospective hospital based study was carried out in two tertiary care centers (Sheth V.S. General Hospital and Smt. S.C.L. Municipal Hospital) over a period of 2 years from July 2013 to June 2015. Hysterolaparoscopy was done in 300 patients. Women aged 20-40 years with normal hormone profile without male factor infertility were included.Results: Out of 300 cases, 206 (69%) patients had primary infertility. While laparoscopy detected abnormalities in 35% of the cases, significant hysteroscopy findings were noted in 17% of cases. Together, diagnostic hysterolaparoscopy detected abnormalities in 26% of the infertile patients in both groups. While the most common laparoscopic abnormality was endometriosis (14%) and adnexal adhesions (12%) in primary and secondary infertile patients respectively, on hysteroscopy, intrauterine septum was found as the commonest abnormality in both the groups.Conclusions: Hysterolaparoscopy is an effective diagnostic tool for evaluation of certain significant and correctable tubo-peritoneal and intrauterine pathologies like peritoneal endometriosis, adnexal adhesions and subseptate uterus, which are usually missed by other imaging modalities

EF1α and RPL13a represent normalization genes suitable for RT-qPCR analysis of bone marrow derived mesenchymal stem cells

<p>Abstract</p> <p>Background</p> <p>RT-qPCR analysis is a widely used method for the analysis of mRNA expression throughout the field of mesenchymal stromal cell (MSC) research. Comparison between MSC studies, both <it>in vitro </it>and <it>in vivo</it>, are challenging due to the varied methods of RT-qPCR data normalization and analysis. Therefore, this study focuses on putative housekeeping genes for the normalization of RT-qPCR data between heterogeneous commercially available human MSC, compared with more homogeneous populations of MSC such as MIAMI and RS-1 cells.</p> <p>Results</p> <p>Eight genes including; <it>ACTB, B2M, EF1α, GAPDH, RPL13a, YWHAZ, UBC </it>and <it>HPRT1 </it>were tested as possible housekeeping genes based on their expression level and variability. <it>EF1α </it>and <it>RPL13a </it>were validated for RT-qPCR analysis of MIAMI cells during expansion in varied oxygen tensions, endothelial differentiation, neural precursor enrichment, and during the comparison with RS-1 cells and commercially available MSC. <it>RPL13a </it>and <it>YWHAZ </it>were validated as normalization genes for the cross-species analysis of MIAMI cells in an animal model of focal ischemia. <it>GAPDH</it>, which is one of the most common housekeeping genes used for the normalization of RT-qPCR data in the field of MSC research, was found to have the highest variability and deemed not suitable for normalization of RT-qPCR data.</p> <p>Conclusions</p> <p>In order to make comparisons between heterogeneous MSC populations, as well as adult stem cell like MSC which are used in different laboratories throughout the world, it is important to have a standardized, reproducible set of housekeeping genes for RT-qPCR analysis. In this study we demonstrate that <it>EF1α</it>, <it>RPL13a </it>and <it>YWHAZ </it>are suitable genes for the RT-qPCR analysis and comparison of several sources of human MSC during <it>in vitro </it>characterization and differentiation as well as in an <it>ex vivo</it> animal model of global cerebral ischemia. This will allow for the comparative RT-qPCR analysis of multiple MSC populations with the goal of future use in animal models of disease as well as tissue repair.</p

New mechanistic insights, novel treatment paradigms, and clinical progress in cerebrovascular diseases

The past decade has brought tremendous progress in diagnostic and therapeutic options for cerebrovascular diseases as exemplified by the advent of thrombectomy in ischemic stroke, benefitting a steeply increasing number of stroke patients and potentially paving the way for a renaissance of neuroprotectants. Progress in basic science has been equally impressive. Based on a deeper understanding of pathomechanisms underlying cerebrovascular diseases, new therapeutic targets have been identified and novel treatment strategies such as pre- and post-conditioning methods were developed. Moreover, translationally relevant aspects are increasingly recognized in basic science studies, which is believed to increase their predictive value and the relevance of obtained findings for clinical application.This review reports key results from some of the most remarkable and encouraging achievements in neurovascular research that have been reported at the 10th International Symposium on Neuroprotection and Neurorepair. Basic science topics discussed herein focus on aspects such as neuroinflammation, extracellular vesicles, and the role of sex and age on stroke recovery. Translational reports highlighted endovascular techniques and targeted delivery methods, neurorehabilitation, advanced functional testing approaches for experimental studies, pre-and post-conditioning approaches as well as novel imaging and treatment strategies. Beyond ischemic stroke, particular emphasis was given on activities in the fields of traumatic brain injury and cerebral hemorrhage in which promising preclinical and clinical results have been reported. Although the number of neutral outcomes in clinical trials is still remarkably high when targeting cerebrovascular diseases, we begin to evidence stepwise but continuous progress towards novel treatment options. Advances in preclinical and translational research as reported herein are believed to have formed a solid foundation for this progress

Nicotine addiction causes unique detrimental effects on women's brains

Nicotine addiction produces diverse physiological effects common to both men and women because of activation of the nicotinic acetylcholine receptors. In addition to these effects, nicotine reduces circulating estrogen (the female sex hormone) levels and leads to early onset of menopause in women. Nicotine's effect on estrogen metabolism has potential far-reaching consequences because endogenous circulating estrogen helps prevent cerebrovascular diseases in premenopausal women. In this article, the author presents a survey of literature showing that nicotine addiction causes unique deleterious effects in women's brains by inhibiting estrogen signaling, which makes the brain more susceptible to ischemic brain damage

The peri-menopause in a woman’s life: a systemic inflammatory phase that enables later neurodegenerative disease

The peri-menopause or menopausal transition—the time period that surrounds the final years of a woman’s reproductive life—is associated with profound reproductive and hormonal changes in a woman’s body and exponentially increases a woman’s risk of cerebral ischemia and Alzheimer’s disease. Although our understanding of the exact timeline or definition of peri-menopause is limited, it is clear that there are two stages to the peri-menopause. These are the early menopausal transition, where menstrual cycles are mostly regular, with relatively few interruptions, and the late transition, where amenorrhea becomes more prolonged and lasts for at least 60 days, up to the final menstrual period. Emerging evidence is showing that peri-menopause is pro-inflammatory and disrupts estrogen-regulated neurological systems. Estrogen is a master regulator that functions through a network of estrogen receptors subtypes alpha (ER-α) and beta (ER-β). Estrogen receptor-beta has been shown to regulate a key component of the innate immune response known as the inflammasome, and it also is involved in regulation of neuronal mitochondrial function. This review will present an overview of the menopausal transition as an inflammatory event, with associated systemic and central nervous system inflammation, plus regulation of the innate immune response by ER-β-mediated mechanisms

Simultaneous nicotine and oral contraceptive exposure alters brain energy metabolism and exacerbates ischemic stroke injury in female rats

Smoking-derived nicotine (N) and oral contraceptives (OC) synergistically exacerbate ischemic brain damage in the females and underlying mechanisms remain elusive. Our published study showed that N toxicity is exacerbated by OC via altered mitochondrial function owing to a defect in the activity of cytochrome c oxidase. Here, we investigated the global metabolomic profile of brains of adolescent female Sprague-Dawley rats exposed to N ± OC. Rats were randomly exposed to saline or N + /−OC for 16–21 days followed by random allocation into two cohorts. One cohort underwent transient middle cerebral artery occlusion and histopathology was performed 30 days later. From the second cohort, cortical tissues were collected for an unbiased global metabolomic profile. Pathway enrichment analysis showed significant decrease in glucose, glucose 6-phosphate and fructose-6-phosphate, along with a significant increase in pyruvate in the N + /−OC exposed groups when compared to saline (p < 0.05), suggesting alterations in the glycolytic pathway which were confirmed by Western blot analyses of glycolytic enzymes. Infarct volume quantification showed a significant increase following N alone or N + OC as compared to saline control. Because glucose metabolism is critical for brain physiology, altered glycolysis deteriorates neural function, thus exacerbating ischemic brain damage

Abstract P799: Nicotine Along With Oral Contraceptive Exposure Alters Brain Lipid Metabolism and Exacerbates Ischemic Injury in Female Rats

Background: Smoking-derived nicotine (N) and oral contraceptives (OC) synergistically exacerbate both global and focal ischemic brain damage in females. While the underlying mechanisms remain elusive, our published study showed that OC exacerbate N toxicity via altered mitochondrial electron transport chain function. Because mitochondria play a central role in cellular metabolism, we examined the metabolic fingerprint of adolescent and adult female rat brains exposed to N +/- OC. Methods: Adolescent (6 weeks old) and adult (12 weeks old) Sprague-Dawley female rats were randomly (n = 8/group) exposed to either saline, N (4.5 mg/kg) +/- OC for 16-21 days. Following treatment, brain tissue was harvested for unbias metabolomic analysis (performed by Metabolon Inc.). The metabolomic profile was complemented with western blot analysis and enzyme activity measurements. Results: Pathway enrichment analysis showed significant alterations in lipid metabolism. Adolescent but not adult females treated with N, OC and N+OC compared to saline showed significant increases in carnitine conjugated fatty acid metabolites such as arachidonoylcarnitine (C20:4), docosahexaenoylcarnitine (C22:6) and stearoylcarnitine (C18). These changes in fatty acyl carnitines were accompanied by an increase in a subset of free fatty acids, suggesting elevated fatty acid β-oxidation in the mitochondria to meet energy demand. In support, 3-hydroxybutyrate (BHBA) was significantly lower in OC and N+OC treatment group in adolescent animals, implying a complete shunting of acetyl CoA for energy production via TCA cycle. BHBA is a ketone body that increases in concentration as lipid oxidation rates increase with acetyl CoA accumulation. Reduced BHBA levels may also suggest mitochondrial dysfunction in response to OC and N+OC treatment. Conclusion: The observed changes in the metabolic fingerprint and fatty acid metabolism reflect a general alteration in energy metabolism with nicotine treatment exclusively in young animals and these changes are enhanced by N+OC treatment. Discerning the exact effects of N +/- OC on overall brain metabolism and the molecular mechanisms affecting mitochondrial function at different ages will open a new window for future therapeutic intervention

Xenoestrogens impact brain estrogen receptor signaling during the female lifespan: A precursor to neurological disease?

Xenoestrogens, foreign synthetic chemicals mimicking estrogens, are lurking in our surroundings. Climate change may alter their toxicity and bioavailability. Since xenoestrogens have extremely high lipid solubility and are structurally similar to natural endogenous estrogens, they can bind to estrogen receptors (ERs) -alpha (ER-α) and -beta (ER-β). Scientific evidence accumulated over the past decades have suggested that natural 17β-estradiol (E2; a potent estrogen), via activation of its receptors, plays a pivotal role in regulation of brain development, differentiation, metabolism, synaptic plasticity, neuroprotection, cognition, anxiety, body temperature, feeding and sexual behavior. In the brain, ER-β is predominantly expressed in the various regions, including cerebral cortex and hippocampus, that have been shown to play a key role in cognition. Therefore, disturbances in function of ER-β mediated E2 signaling by xenoestrogens can lead to deleterious effects that potentiate a variety of neurological diseases starting from prenatal to post-menopause in women. The goal of this review is to identify the possible neurological effects of xenoestrogens that can alter estrogen receptor-mediated signaling in the brain during different stages of the female lifespan