Design, synthesis, biological evaluation and molecular dynamics of some novel 3-phenylpyrazolo[1,5-a]pyrimidine-2,7(1H,4H)-dione based compounds as anti-tubercular agents.

Decaprenylphosphoryl-ß-d-ribose-2'-epimerase (DprE1) is a druggable target which is being exploited for the development of new anti-TB agents. In the present work, we report developing a pharmacophore model and performing virtual screening of Asinex database using the developed pharmacophore model to get eight hits as potential DprE1 inhibitors. The hits were used as leads to design new 3-phenylpyrazolo[1,5-a]pyrimidine-2,7(1H,4H)-dione based potential anti-TB agents. On the basis of the identified lead molecules, a total of 18 compounds were synthesized and evaluated for their anti-TB activity by using MABA. ADMET predictions for all the compounds revealed that these compounds have drug-like and lead-like properties. One of the final compounds was found to exhibit potent anti-TB activity against Mycobacterium bovis.Communicated by Ramaswamy H. Sarma.

Medicines as Common Commodities or Powerful Potions? What Makes Medicines Reusable in People's Eyes.

BACKGROUND: Medicines reuse involves dispensing quality-checked, unused medication returned by one patient for another, instead of disposal as waste. This is prohibited in UK community pharmacy because storage conditions in a patient's home could potentially impact on the quality, safety and efficacy of returned medicines. Our 2017 survey examining patients' intentions to reuse medicines found many favoured medicines reuse. Our aim was to analyse the qualitative comments to explore people's interpretations of what makes medicines (non-)reusable. METHODS: Thematic analysis was used to scrutinize 210 valid qualitative responses to the survey to delineate the themes and super-ordinate categories. RESULTS: Two categories were "medicines as common commodities" versus "medicines as powerful potions". People's ideas about medicines aligned closely with other common commodities, exchanged from manufacturers to consumers, with many seeing medicines as commercial goods with economic value sanctioning their reuse. Fewer of the comments aligned with the biomedical notion of medicines as powerful potions, regulated and with legal and ethical boundaries limiting their (re)use. CONCLUSION: People's pro-medicines-reuse beliefs align with perceptions of medicines as common commodities. This helps explain why patients returning their medicines to community pharmacies want these to be recycled. It could also explain why governments permit medicines reuse in emergencies.

Recent developments and strategies for the discovery of TACE inhibitors.

INTRODUCTION: TNF-α plays a central role in certain autoimmune diseases as well as in inflammation. The current strategy for excluding TNF-α from circulation is to selectively inhibit TNF-α converting enzyme (TACE), an enzyme that cleaves mTNF-α to active TNF-α. Various TACE inhibitors have been discovered by using different strategies to control inflammatory diseases, cancer, and cardiac hypertrophy. AREAS COVERED: The present article summarizes the design and discovery of novel TACE inhibitors that have been reported in the literature since 2012 onwards. It also includes some reports concerning the new role that TACE plays in cancer and cardiac hypertrophy. EXPERT OPINION: So far, undertaken studies that have looked to design and develop small TACE inhibitors have been discouraging due to the failure of any TACE inhibitors to hit the market. However, some of the latest developments, such as with tartrate-based inhibitors, has given hope to the potentiality of a viable novel selective TACE inhibitor therapeutic in the future. Indeed, some of the novel peptidomimetics and monoclonal antibodies have great potential to pave the way for an effective and safe therapy by selectively inhibiting TACE enzyme.

Levonorgestrel intrauterine system: Current role in management of heavy menstrual bleeding.

A review of literature was conducted to report on the effectiveness of levonorgestrel intrauterine system (LNG-IUS) in women with heavy menstrual bleeding (HMB). The relevant data were obtained by computerized searches of PubMed up to December 2012 and other references available with the authors. Information was obtained from references listed. Studies and case reports were excluded if they did not specifically provide information about LNG-IUS usage in women with HMB. After perusal, each relevant publication was summarized and appraised in terms of whether it contained information relevant to the stated objective. Available data shows that LNG-IUS therapy is effective and safe, providing significant reduction of menstrual bleeding in patients with HMB. LNG-IUS is a good strategy to reduce the number of hysterectomies in women with HMB.

Pregnancy in Type 1 Diabetes Mellitus: How Special are Special Issues?

India leads the world with largest number of diabetics earning the dubious distinction of "the diabetes capital of the world." Diabetes is associated with maternal and perinatal morbidity and mortality. The number of pregnant women with pre-existing diabetes is increasing, mainly from an increase in type 2 diabetes, but also an increase in type 1 diabetes. Overall, type 1 diabetes accounts for approximately 5% to 10% of all diabetes outside of pregnancy, and in pregnancy put together with type 2 account for 10% of diabetic pregnancies. Management of the pregnant diabetic woman is a complex task that ideally begins before conception. Specific attention is required for diabetic pregnancies in different trimesters of pregnancy. Diabetes, especially type 1 diabetes, can be a challenge in pregnancy, but with education, close monitoring, and latest therapeutic modalities, these women can have healthy newborns. Close attention to diet, glycemic control, metabolic stresses, and early diagnosis and monitoring of complications can make pregnancy a successful experience for women with diabetes. A MedLine search was done to review relevant articles in English literature on diabetes and pregnancy, and specific issues related to pregnancy in type 1 diabetes were reviewed.

Sexuality in midlife: Where the passion goes?

Women's sexuality is highly capricious and multifaceted. Sexual functioning is an imperative component of women's lives and has progressively received public health, medical and even pharmaceutical attention. Sexual functioning, however, declines with age, leading to much debate about the contribution of menopause to sexual activity and functioning among women. The past two decades have witnessed an explosion of research into female sexuality. It is now understood that healthy and satisfying sexual function may extend all through the life cycle, and does not finish with end of child bearing years. Very few women's healthcare physicians are adequately trained to monitor a woman's sexual health through her menopausal transition and beyond, much less how to treat the sexual problems that can arise during this special time. The strong association of physical health and psycho-social factors with sexual functioning accentuates the clinical domineering to explore these factors when discussing women's apprehensions regarding sexual dysfunction. It is need of hour to create scientific evidence to help women's health care physicians understand the requirements of women in these special years of her life and help deliver the care they need and so rightly, deserve.

Stress urinary incontinence: What, when, why, and then what?

Stress urinary incontinence (SUI) has a significant impact on the quality of life for many women. Most women do not seek medical attention for this condition. Treatment for this problem includes initial conservative therapies and then surgery is an option. More than 200 surgical procedures have been described in the literature for the treatment of stress incontinence. The gold-standard surgical treatment of SUI in patients with a mobile bladder neck and normally functioning urethra has been accomplished through a retropubic approach using either a Burch or Marshall-Marchetti-Krantz procedure. By the absolute success of Trans obturator tape (TOT) application in treatment of SUI and the niche it has created for itself in the maze of treatment modalities available for SUI, there seems to be little doubt that TOT is all set to become the new Gold Standard for treatment of SUI in times to come. It is difficult to imagine any further improvements in the midurethral sling procedures or surgeries for SUI. However 10 years ago, no one could have imagined the progress and development that has been seen over these few short years in the treatment of SUI. The future may hold promise in technologies such as stem cells that may be injected in or around the urethral support structures and provide regeneration of the lacking support structures. What so ever, it's definitely time to provide millions of women with knowledge that empowers them to make lifestyle changes to decrease their risk of SUI and to understand the reality that they are not alone if they have SUI.