Choosing an oestrogen replacement therapy in young adult women with Turner syndrome

OBJECTIVE Hormone replacement therapy (HRT) is prescribed to most patients with Turner syndrome (TS) although its use in adult TS patients has not been scientifically evaluated. The present study was performed to compare the short‐term effects in adult women with Turner syndrome of low‐dose oral conjugated oestrogen (0·625 mg, CE) with relatively high dose ethinyl oestradiol (30 µg, EE2); both combined with an oral progestin. DESIGN and PATIENTS After 4 months off HRT, 17 young, otherwise healthy women with TS were enrolled in a random, unblinded, crossover study of the two oestrogenic preparations, each given for 6 months. MEASUREMENTS We compared parameters of oestrogenic activity that would cover immediate changes in hormone levels, biochemistry, bone turnover, uterine and cardiac variables, which constitute risk factors for later development of diabetes, atherosclerosis, osteoporosis and aortic dissection. RESULTS Serum FSH returned to normal follicular phase levels only on the EE2 regimen. The hypotrophic endometria normalized with either of the two oestrogen regimens with no excessive hypertrophy. Hyperinsulinaemia was suppressed to normal by both EE2 and CE. PTH and 1,25‐dihydroxyvitamin D levels increased on HRT (EE2 > CE), and phosphorus decreased. Alkaline phosphatase, osteocalcin and urinary deoxypyridinoline cross‐links (DPD) were high off therapy; the former two suppressed to high–normal levels on the EE2 regimen, but not on CE, and DPD did not normalize with either HRT. Lipid profiles in these young TS patients were normal. Liver enzymes were mildly elevated off therapy and suppressed to normal levels on both regimens, but more so with EE2. CONCLUSIONS The risk factors embodied in hyperinsulinaemia and enhanced bone turnover which, ultimately, have consequences for TS morbidity, are minimized by HRT. In the short term, neither regimen is effective for bone turnover in adult women with Turner syndrome.     

Controller for an Axial Flow Blood Pump

Abstract: A rotary blood pump inherently provides only one noninvasive "observable'" parameter (motor current) and allows for only one "controllable" parameter (pump speed). To maintain the systemic circulation properly, the pump speed must be controlled to sustain appropriate outlet Hows and perfusion pressure while preventing pulmonary damage caused by extremes in preload. Steady-state data were collected at repeated intervals during chronic trials of the Nimbus AxiPump (Nimbus, Inc., Rancho Cordova, California, U.S.A.) in sheep (n = 7) and calves (n = 12). For each data set, the pump speed was increased at increments of 500 rpm until left ventricular and left atrial emptying was observed by left atrial pressure diminishing to zero. The effect of decreasing preload was evaluated perioperatively by inferior vena cava occlusion at a constant pump speed. Fourier analysis established a relationship between changes in the pump preload and the power spectra of the pump current waveform. Based on these results, a control method was devised to avoid ventricular collapse and maintain the preload within a physiologic range. The objective of this controller is the minimization of the second and third harmonic of the periodic current waveform. This method is intended to provide a noninvasive regulation of the pump by eliminating the need for extraneous transducers.     

Using stakeholder analysis to support moves towards universal coverage: lessons from the SHIELD project

Stakeholder analysis is widely recommended as a tool for gathering insights on policy actor interests in, positions on, and power to influence, health policy issues. Such information is recognized to be critical in developing viable health policy proposals, and is particularly important for new health care financing proposals that aim to secure universal coverage (UC). However, there remain surprisingly few published accounts of the use of stakeholder analysis in health policy development generally, and health financing specifically, and even fewer that draw lessons from experience about how to do and how to use such analysis. This paper, therefore, aims to support those developing or researching UC reforms to think both about how to conduct stakeholder analysis, and how to use it to support evidence-informed pro-poor health policy development. It presents practical lessons and ideas drawn from experience of doing stakeholder analysis around UC reforms in South Africa and Tanzania, combined with insights from other relevant material. The paper has two parts. The first presents lessons of experience for conducting a stakeholder analysis, and the second, ideas about how to use the analysis to support policy design and the development of actor and broader political management strategies. Comparison of experience across South Africa and Tanzania shows that there are some commonalities concerning which stakeholders have general interests in UC reform. However, differences in context and in reform proposals generate differences in the particular interests of stakeholders and their likely positioning on reform proposals, as well as in their relative balance of power. It is, therefore, difficult to draw cross-national policy comparisons around these specific issues. Nonetheless, the paper shows that cross-national policy learning is possible around the approach to analysis, the factors influencing judgements and the implications for, and possible approaches to, management of policy processes. Such learning does not entail generalization about which UC reform package offers most gain in any setting, but rather about how to manage the reform process within a particular context.     

Computer-aided design of selective Cytochrome P450 inhibitors and docking studies of alkyl resorcinol derivatives

The present investigation is aimed to understand the interactive mechanism that occurs between the active site of Cytochrome P450 and its inhibitors by molecular modeling studies. Based on the docking studies and information obtained from interaction analysis, structure-based virtual screening was performed by selecting 217 new potential inhibitors with structural diversity using GOLD and ArgusLab molecular docking softwares. Among a total of 217 compounds, only 21 molecules were considered as the potential inhibitors. Hydrogen bond and van der Waals interaction between various active site residues like ARG 382, HIS447, CYS449, ASN493, TYR131, and TYR92 of Cytochrome P450 were observed. Docking studies of selected resorcinols showed an optimal molecular environment which is required to bind with active sites of Cytochrome P450. Hydroxyl groups of resorcinols exhibited van der Waals interactions with certain active sites. To estimate the drug-likeness properties the parameters like partition coefficient (log P), tabulated molecular polar surface area (TPSA), and bio activity score were obtained from the Molinspiration studies. Based on docking and Molinspiration data analysis, the molecules 10, 3, 18, 19, and 7 were found to be highly potent inhibitors of Cytochrome P450.     

Holy Basil leaf extract decreases tumorigenicity and metastasis of aggressive human pancreatic cancer cells in vitro and in vivo: Potential role in therapy

There is an urgent need to develop alternative therapies against lethal pancreatic cancer (PC). Ocimum sanctum (“Holy Basil”) has been used for thousands of years in traditional Indian medicine, but its anti-tumorigenic effect remains largely unexplored. Here, we show that extracts of O. sanctum leaves inhibit the proliferation, migration, invasion, and induce apoptosis of PC cells in vitro. The expression of genes that promote the proliferation, migration and invasion of PC cells including activated ERK-1/2, FAK, and p65 (subunit of NF-κB), was downregulated in PC cells after O. sanctum treatment. Intraperitoneal injections of the aqueous extract significantly inhibited the growth of orthotopically transplanted PC cells in vivo (p < 0.05). Genes that inhibit metastasis (E-cadherin) and induce apoptosis (BAD) were significantly upregulated in tumors isolated from mice treated with O. sanctum extracts, while genes that promote survival (Bcl-2 and Bcl-xL) and chemo/radiation resistance (AURKA, Chk1 and Survivin) were downregulated. Overall, our study suggests that leaves of O. sanctum could be a potential source of novel anticancer compounds in the future.