We have previously shown that individual β-amino acid substitution in angiotensin (Ang) II reduced Ang II type 1 receptor (AT1R) but not Ang II type 2 receptor (AT2R)-binding and that the heptapeptide Ang III exhibited greater AT2R:AT1R selectivity than Ang II. Therefore, we hypothesized that β-amino-acid-substituted Ang III peptide analogues would yield highly selective AT2R ligands, which we have tested in binding and functional vascular assays. In competition binding experiments using either AT1R- or AT2R-transfected human embryonic kidney (HEK)-293 cells, novel β-substituted Ang III analogues lacked appreciable AT1R affinity, whereas most compounds could fully displace (125)I-Sar(1)Ile(8) Ang II from AT2R. The rank order of affinity at AT2R was CGP42112 > Ang III > β-Pro(7) Ang III=Ang II > β-Tyr(4) Ang III ≥ PD123319 >> β-Phe(8) Ang III >> β Arg(2) Ang III=β-Val(3) Ang III >> β-Ile(5) Ang III. The novel analogue β-Pro(7) Ang III was the most selective AT2R ligand tested, which was >20,000-fold more selective for AT2R than AT1R. IC50 values at AT2R from binding studies correlated with maximum vasorelaxation in mouse aortic rings. Given that β-Pro(7) Ang III was an AT2R agonist, we compared β-Pro(7) Ang III and native Ang III for their ability to reduce blood pressure in separate groups of conscious spontaneously hypertensive rats. Whereas Ang III alone increased mean arterial pressure (MAP), β-Pro(7) Ang III had no effect. During low-level AT1R blockade, both Ang III and β-Pro(7) Ang III, but not Ang II, lowered MAP (by ∼30 mmHg) at equimolar infusions (150 pmol/kg/min for 4 h) and these depressor effects were abolished by the co-administration of the AT2R antagonist PD123319. Thus, β-Pro(7) Ang III has remarkable AT2R selectivity determined in binding and functional studies and will be a valuable research tool for insight into AT2R function and for future drug development.

BackgroundMore than 340 million cases of curable sexually transmitted infections (STIs) were estimated to have occurred worldwide in 1995. Previous studies have shown that the presence of other concomitant STIs increases the likelihood of HIV transmission. The first national study of STIs conducted in Pakistan in 2004 revealed a high burden of STIs among women selling sex. The HIV epidemic in Pakistan has thus far followed the "Asian epidemic model". Earlier studies among women selling sex have shown a low prevalence of HIV coupled with a low level of knowledge about AIDS. The aim of our study was to estimate the prevalence of HIV and STIs, and assess knowledge and risk behaviours related to HIV/STI, among women selling sex in Lahore, Pakistan.MethodsA total of 730 participants were recruited through respondent-driven sampling. The participants were women selling sex in three areas (referred to as "A", "B", and "C") of Lahore. A structured questionnaire addressing demographic information, sexual life history, sexual contacts, and knowledge and practices related to HIV/STI prevention was administered by face-to-face interview. Biological samples were obtained from all participants and tested for HIV, Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis. Pearson's chi-square and multivariable logistic regression analysis were performed to test associations between potential risk factors and specified diagnosed infections.ResultsThe prevalence of HIV infection was 0.7%, T pallidum 4.5%, N gonorrhoeae 7.5%, C trachomatis 7.7% and T vaginalis 5.1%. The participants had been selling sex for a median period of seven years and had a median of three clients per day. Sixty five percent of the participants reported that they "Always use condom". The median fee per sexual contact was Rs. 250 (3 Euro). Compared to Areas A and C, women selling sex in Area B had a significantly higher risk of chlamydial infection, gonorrhoea and trichomoniasis. Among the participants, 37% had correct knowledge about HIV/AIDS transmission and its prevention.ConclusionsThe prevalence of HIV was <1%, and of any other STI 18.5% among participating women selling sex in Lahore, Pakistan. A reasonably high condom use, a relatively low number of sexual partners, and a relatively low prevalence of STIs might have contributed to the low HIV prevalence.

Our aim for this study was to explore the factors influencing women to initiate and continue as sex workers and to explore their perceptions about human immuno deficiency virus/acquired immune deficiency syndrome (HIV/AIDS), sexually transmitted infections (STIs), and health seeking behavior. We conducted a qualitative study based on interviews with 20 purposively selected women selling sex. Content analysis of data resulted in identification of one main theme: "Poverty of opportunity forcing women into prostitution." The identified driving forces behind women resorting to sell sex were poverty, materialism, and the desire to move up in society. They continued to sell sex due to poverty of opportunity and influencing social factors.

European evidence-based guidelines for the treatment and management of chronic pancreatitis (CP) have been made available following the harmonizing diagnosis and treatment of CP across Europe (HaPanEU) initiative by the United European Gastroenterology (UEG). The aim of this study was to evaluate adherence to the guideline recommendations in the management of patients with pancreatic exocrine insufficiency (PEI) at Karolinska University Hospital in Stockholm. UEG guideline recommendations were evaluated and categorized into 55 different quality indicators (QIs). Data from a retrospective cohort of CP patients being treated at Karolinska University Hospital were evaluated with regard to overall adherence as well as adherence to specific QIs. A total number of 118 patients out of 956 patients diagnosed with CP were eligible for inclusion with mean overall adherence of 61.9% to the defined QIs. A significant difference in mean overall adherence was shown between patients diagnosed with CP prior to 1 January 2016 and following 1 January 2016 (59.3% and 67.7% respectively, p = 0.004), with linear regression analysis also demonstrating improvement correlating to date of diagnosis (p = 0.002). In conclusion, diagnosis and treatment of PEI improved after the HaPanEU guidelines became available and is continuously improving; however, there is room for further improvement.

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