Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and is the leading cause of anovulatory subfertility.Increased gonadotrophin releasing hormone (GnRH) pulsatility in the hypothalamus results in preferential luteinizing hormone (LH) secretion from the pituitary gland, leading to ovarian hyperandrogenism and oligo/anovulation.The resultant hyperandrogenism reduces negative feedback from sex steroids such as oestradiol and progesterone to the hypothalamus, and thus perpetuates the increase in GnRH pulsatility. GnRH neurons do not have receptors for oestrogen, progesterone, or androgens, and thus the disrupted feedback is hypothesized to occur via upstream neurons. Likely candidates for these upstream regulators of GnRH neuronal pulsatility are Kisspeptin, Neurokinin B (NKB), and Dynorphin neurons (termed KNDy neurons). Growing insight into the neuroendocrine dysfunction underpinning the heightened GnRH pulsatility seen in PCOS has led to research on the use of pharmaceutical agents that specifically target the activity of these KNDy neurons to attenuate symptoms of PCOS. This review aims to highlight the neuroendocrine abnormalities that lead to increased GnRH pulsatility in PCOS, and outline data on recent therapeutic advancements that could potentially be used to treat PCOS. Emerging evidence has investigated the use of neurokinin 3 receptor (NK3R) antagonists as a method of reducing GnRH pulsatility and alleviating features of PCOS such as hyperandrogenism. We also consider other potential mechanisms by which increased GnRH pulsatility is controlled, which could form the basis of future avenues of research.

Bacterial and fungal infections still remain an important cause of mortality in patients with hematological malignancies and in recipients of hematopoietic stem cell transplants (HSCT) especially in developing countries like India. Granulocyte transfusions (GTX) from healthy donors may lead to early clearance of index infection and thus prevent mortality. The aim of the present study was to evaluate the efficacy of GTX in combating life-threatening infections and preventing mortality in patients of hematological disorders/recipients of HSCT with severe neutropenia. This study was a prospective, observational analysis of patients with different hematological disorders/recipients of HSCT, who received GTX from January 2014 to December 2017. All patients had an Absolute neutrophil Count (ANC) < 0.5 x 109/L and a life threatening sepsis defined by presence of hemodynamic instability/ impending septic shock/ continuous high fever despite the use of the highest line of antimicrobials. A total of 143 granulocyte collections were done for 66 infectious episodes (IEs) in 60 patients. Multidrug resistant organisms (MDROs) were observed in 47/66 IEs (71.2%) and fungal infections were seen in 9/66 IEs (13.6%). Resolution of index infection after GTX was seen in 45/66 IEs (68.2%), and the 30 day overall survival (OS) was 67.7%. OS was significantly higher in patients who received GTX within 7 days of neutropenic sepsis (p = 0.01). Patients with MDROs who received early GTX therapy had a better OS as compared to those who received late GTX (p = 0.02). GTX were well tolerated and only 6 patients’ developed mild features of transfusion related acute lung injury (TRALI) which was managed conservatively, and 1 patient demonstrated hypocalcemic tetany. GTX may be of particular relevance in countries like India, where the incidence of infections is very high in neutropenic patients and there is an increasing emergence of MDROs.

In vitro antibacterial potential of the chloroform, ethyl acetate, hexane, methanol and aqueous extracts of Calotropis gigantia (L.) R. Br. was evaluated by using five cariogenic bacteria, Actinomyces viscosus, Lactobacillus acidophilus, Lactobacillus casei, Streptococcus mitis and Streptococcus mutans. Agar well diffusion method and minimum inhibitory concentration (MIC) were used for this purpose. The chloroform extracted fraction of latex showed inhibitory effect against S. mutans and L. acidophilus with MIC value of 0.032 and 0.52 mg/mL, respectively. Qualitative investigation on structure elucidation of bioactive compound using IR, NMR and GC-MS techniques revealed the presence of methyl nonanoate, a saturated fatty acid.

Context:Antimicrobial proteins and peptides constitute a diverse class of host-defense molecules that act early to combat invasion and infection with bacteria and other microorganisms. Among the various antimicrobial peptides in the oral cavity, adrenomedullin (ADM), a cationic peptide, is found in gingival crevicular fluids (GCFs) in amounts twice as high in periodontal disease sites as healthy sites. Studies have also shown that plasma levels of ADM increased in patients with type 2 diabetes mellitus as compared with controls.Aims:This clinico-biochemical study was undertaken to try to decipher the probable link between ADM, diabetes and periodontitis.Materials and Methods:The study comprised of 90 patients who were divided into three groups based on community periodontal index scores and diabetes status. Probing pocket depth and clinical attachment level were measured in all subjects. GCF was collected from all the participants using micropipettes and blood samples were collected from subjects in Groups III, for analysis of glycated hemoglobin. ADM levels were measured in GCF samples by the enzyme-linked immunosorbent assay.Statistical Analysis Used:The data obtained were subjected to analysis of variance, Bonferroni test and Pearson's correlation.Results:An increase in GCF levels of ADM from periodontal health to disease and in periodontitis patients with type 2 diabetes was noted.Conclusions:Increase in GCF levels of ADM from periodontal health to disease and in periodontitis patients with type 2 diabetes reinforces the perio-systemic interlink concept.

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