Gonadotropin releasing hormone in first trimester human placenta: isolation, partial characterisation and in vitro biosynthesis

Using a specific radioimmunoassay for gonadotropin releasing hormone, the presence of gonadotropin releasing hormone like material in the first trimester human placenta has been demonstrated. The material has been partially characterized using carboxy methyl cellulose chromatography, high pressure gel permeation chromatography and reverse phase C18 high pressure liquid chromatographic analysis. Analysis for bioactivity revealed that placental gonadotropin releasing hormone is much more active than synthetic gonadotropin releasing hormone in in vitro rat pituitary lutinising hormone release assay. In vitro biosynthetic studies using labelled precursors and immunoaffinity chromatography indicated that first trimester human placenta synthesizes gonadotropin releasing hormone like material

Regulation of DNA synthesis and the cell cycle in human prostate cancer cells and lymphocytes by ovine uterine serpin

<p>Abstract</p> <p>Background</p> <p>Uterine serpins are members of the serine proteinase inhibitor superfamily. Like some other serpins, these proteins do not appear to be functional proteinase inhibitors. The most studied member of the group, ovine uterine serpin (OvUS), inhibits proliferation of several cell types including activated lymphocytes, bovine preimplantation embryos, and cell lines for lymphoma, canine primary osteosarcoma and human prostate cancer (PC-3) cells. The goal for the present study was to evaluate the mechanism by which OvUS inhibits cell proliferation. In particular, it was tested whether inhibition of DNA synthesis in PC-3 cells involves cytotoxic actions of OvUS or the induction of apoptosis. The effect of OvUS in the production of the autocrine and angiogenic cytokine interleukin (IL)-8 by PC-3 cells was also determined. Finally, it was tested whether OvUS blocks specific steps in the cell cycle using both PC-3 cells and lymphocytes.</p> <p>Results</p> <p>Recombinant OvUS blocked proliferation of PC-3 cells at concentrations as low as 8 μg/ml as determined by measurements of [³H]thymidine incorporation or ATP content per well. Treatment of PC-3 cells with OvUS did not cause cytotoxicity or apoptosis or alter interleukin-8 secretion into medium. Results from flow cytometry experiments showed that OvUS blocked the entry of PC-3 cells into S phase and the exit from G₂/M phase. In addition, OvUS blocked entry of lymphocytes into S phase following activation of proliferation with phytohemagglutinin.</p> <p>Conclusion</p> <p>Results indicate that OvUS acts to block cell proliferation through disruption of the cell cycle dynamics rather than induction of cytotoxicity or apoptosis. The finding that OvUS can regulate cell proliferation makes this one of only a few serpins that function to inhibit cell growth.</p

Återvinning av motorvärme i lastbilsmotorergenom att kombinera ett evaporativt motorkylningssystemmed en Rankine-cykel.

Engine Cooling losses constitutes about 20% of the injected fuel energy in a modern heavy duty truck diesel engine. The objective of this Master Thesis Project is to investigate flow boiling cooling as a thermally efficient method for waste heat recovery as well as a good solution for precision cooling. First, an engine heat transfer model was implemented on GT-suite software in order to estimate heat fluxes within the engine cylinder. Liners being less thermally constrained than the cylinder head, flow boiling cooling was then investigated in the liner’s water jackets. A more adapted heat transfer model taking into account both gas side and cooling side of the liner was thus implemented on Simulink. Unlike commercials software, this simple model allowed to implement the relevant two-phase heat transfer correlations and to study in details the boiling flow behaviors. The hydraulic diameter of the water jackets, the fluid saturated pressure and the surface area of heat transfer are the major parameters and they were studied for various mass flow rate in order to analyze how they influence wall temperature and heat transfer. This study showed good operating conditions for very low mass flow rate (about 1% of the typical mass flow rate for liquid convective cooling). Due to flow control issues, it implied the consideration of other fluids such as refrigerants but showed good prospect for cooling system simplification. This flow boiling model was finally inserted in a complete Rankine loop model using water as a working fluid to study potential efficiency improvements. A Rankine loop using water as a working fluid would thus improve the heat recovery of the considered engine of about 4.8% of the net engine brake power, recovering heat from the liners and the exhaust gases at 1800RPM, full load. Further simulations have also been led with R245fa, which shows a WHR of about 5.5% of the net engine brake power at 1800RPM, full load.Motorns kylförluster utgör ca 20 % av energin som injiceras i dieselmotorn på en modern lastbil. Målet med detta examensarbete är att undersöka om flödes kokande kylning är en termiskt effektiv metod för att återvinna spillvärmes och en effektiv lösning för precisionskyla. Först genomfördes en motorvärmeöverföringsmodell på GT-suite för att beräkna värmeflöden i motorcylindern. Eftersom cylinderfoder är mindre termiskt begränsade än topplockundersöktes flödes kokande kylning i cylinderfoder. En mer anpassad värmeöverföringsmodell med hänsyn till både avgas- och kylmedelsidan på cylinderfoder genomfördes således med Simulink. Till skillnad från kommersiella programvaror, gör denna enkla modell det möjligt att utföra 2-fas värmeöverföringskorrelationer och studera flödes kokande beteendet i detalj. De viktigaste parametrarna (vattenmantelns hydrauliska diameter, vätsketrycket och ytan av värmeöverföringarna) studerades för olika massflöden för att analysera hur de påverkar väggtemperatur och värmeöverföring. Undersökningen visade goda arbetsförhållanden för mycket låga massflöden (ca 1 % av det typiska massflödet för konvektiv vätskekylning). På grund av problem med flödesregleringen, behövde andra vätskor beaktas som köldmedier men hade god potential för att kyla systemet effektivt. För att studera potentiella förbättringar av energieffektiviteten infördes den flödes kokande modellen slutligen i en komplett modell av en Rankine-krets där vatten användes som kylmedel. En Rankine-krets med vatten skulle förbättra värmeåtervinningen på den avsedda motorn med 4,8 % motorns bromskraft, genom att återvinna värme från cylinderfoder och avgaserna vid 1800 RPM, full belastning. Ytterligare simulationer har också hållits med R245fa, som visar en återvinning av spillvärmen med 5,5 % av motorns bromskraft vid 1800 RPM, full belastning

Gonadotropin-releasing hormone in first trimester human placenta: isolation, partial characterization and in vitro biosynthesis

Using a specific RIA for gonadotropin-releasing hormone (I), the presence of I-like material in the 1st trimester human placenta was demonstrated. The material has been partially characterized using CMC chromatog., high pressure gel permeation chromatog., and reverse-phase C18 HPLC anal. Anal. for bioactivity revealed that placental I is much more active than synthetic I in in vitro rat pituitary LH release assay. In vitro biosynthetic studies using labeled precursors and immunoaffinity chromatog. indicated that 1st trimester human placenta synthesizes I-like material

Gonadotropin-releasing hormone (GnRH) stimulates both secretion and synthesis of human chorionic gonadotropin (hCG) by first trimester human placental minces in vitro

An in vitro system using the minces of placental villi from first trimester human pregnancy (6-10 weeks) has been validated to examine the effect of addition of GnRH and its analogues on hCG secreted into the medium. Addition of low concentration of GnRH or its analogues (1 × 10(-8) M to 1 × 10(-6) M) resulted in an increase in the quantity of hCG in the medium, while addition of high concentrations of GnRH resulted in an inhibitory effect. Of the analogues tested, Buserelin was highly effective in exerting an inhibitory effect. A significant increase in 35S-methionine incorporation into immunoprecipitable hCG was noticed in the presence of GnRH. These results suggests that GnRH stimulates both synthesis and secretion of hCG by first trimester human placenta

Delayed transfer of care from NHS secondary care to primary care in England: its determinants, effect on hospital bed days, prevalence of acute medical conditions and deaths during delay, in older adults aged 65 years and over

Background: The delay in discharge or transfer of care back to the community following an acute admission to the hospital in older adults has long been a recognized challenge in the UK. We examined the determinants and outcomes of delayed transfer of care in older adults. Methods: A prospective observational study was conducted in a district general hospital with a catchment population of 250,000 in England, UK. Those >= 65 years admitted to two care of the elderly wards during February 2007 were identified and prospectively followed-up till their discharge. Data was presented descriptively. Results: 36.7% (58/158) of patients had a delay in transfer of care. They tended to be older, had poorer pre-morbid mobility, and were more likely to be confused at the time of admission. Compared to the 2003 National Audit Report, a significantly higher percentage (29.3%vs.17%) awaited therapist assessments or (27.6%vs.9%) domiciliary care, with a lower percentage (< 1%vs.14%) awaiting further NHS care. Of 18 in-patient deaths, five occurred during the delay. Seven patients developed medical conditions during the delay making them unfit for discharge. The number of extra bed days attributable to delayed discharges in this study was 682 (mean = 4.8) days. Conclusion: Awaiting therapy and domiciliary care input were significant contributing factors in delayed transfer of care. Similar local assessments could provide valuable information in identifying areas for improvement. Based on available current evidence, efficacy driven changes to the organisation and provision of support, for example rapid response delayed discharge services at the time of "fit to discharge" may help to improve the situation

Prognostic Biomarkers in Cardiovascular Diseases

The use of biomarkers as a reliable and reproducible indicative of the risk, severity, and progression of cardiovascular diseases (CVDs) may greatly enhance the prognostic capability of primary healthcare clinicians. In primary healthcare, the realistic and wise use of reliable biomarkers could minimize the time and costs for effective diagnosis and suitable personalized therapy for CVD patients. Therefore, the aim of the present scoping review is to evaluate the prognostic significance of biomarkers in the progression and monitoring of CVDs. The review was conducted according to the PRISMA-ScR guidelines. Eight databases were searched for articles published as of June 2021 using search terms: cardiovascular diseases AND biomarkers AND prognosis. A total of 21 studies were included in this scoping review. This review identified biomarkers BNP, cTnT yielded better accuracy of disease progression prediction in ACS and HF respectively. The availability of CVDs prognostic biomarkers in primary healthcare clinics could promote improved clinical outcomes of patients

ADMET informatics of Tetradecanoic acid (Myristic Acid) from ethyl acetate fraction of Moringa oleifera leaves

In-silico Computer-Aided Drug Design (CADD) often comprehends virtual screening (VS) of datasets of natural pharmaco-active compounds for drug discovery protocols. Plant Based Natural Products (PBNPs) still, remains to be a prime source of pharmaco-active compounds due to their unique chemical structural scaffolds and functionalities with distinct chemical characteristic feature from natural source that are much acquiescent to drug metabolism and kinetics. In the Post-COVID-Era number of publications pertaining to PBNPs and publicly accessible plant based natural product databases (PBNPDBs) has significantly increased. Moreover, PBNPs are important sources of inspiration or starting points to develop novel therapeutic agents. However, a well-structured, in-depth ADME/Tox profile of PBNPs has been limited or lacking for many of such compounds, this hampers the successful exploitation of PBNPs by pharma industries. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties play key roles in the discovery/ development of drugs, pesticides, food additives, consumer products, and industrial chemicals. In the present study, ADMET-informatics of Tetradecanoic Acid (Myristic Acid) from ethyl acetate fraction of Moringa oleifera leaves to predict drug metabolism and pharmacokinetics (DMPK) outcomes has been taken up. This work contributes to the deeper understanding of Myristic acid as major source of drug from commonly available medicinal plant - Moringa oleifera with immense therapeutic potential. The data generated herein could be useful for NP based lead generation programs. Keywords: Moringa oleifera; Secondary Metabolites; Bioactive Substances; Myristic acid (MA); DMPK; ADME/Tox; Natural Products (NPs); PBNPs; PBNPDB