Intake of polyunsaturated fat in relation to mortality among statin users and non-users in the Southern Community Cohort Study.

BACKGROUND AND AIMS: Consumption of polyunsaturated fatty acids (PUFA), especially the n3-series, may protect against cardiovascular disease (CVD), but recent randomized studies have failed to demonstrate these benefits. One of the prevailing hypotheses is that PUFA intake may not confer benefits beyond those provided by statins, but studies comparing statin users to non-users with regard to effects of PUFA are lacking. METHODS AND RESULTS: Black and white men and women (n = 69,559) in the Southern Community Cohort Study were studied. Cox regression models adjusting for age, sex, race, BMI, recruitment site, education, income, smoking, diabetes, and dietary variables were used. RESULTS: At baseline the mean ± SD age was 52 ± 9 years, 60% of participants were women, 54% had hypertension and 16% used statins. We observed modest inverse associations between n3-PUFA and n6-PUFA intake with mortality among non-statin users but not among statin users. In adjusted analyses, the HRs (95% CIs) for all-cause mortality (6,396 deaths over a median of 6.4 years) comparing the highest to the lowest quintile were 0.90 (0.82-1.00) for n3-PUFA and 0.80 (0.70-0.92) for n6-PUFA among non-statin users, whereas they were 1.06 (0.87-1.28) and 0.96 (0.78-1.19) for n3-PUFA and n6-PUFA, respectively, among statin users. CONCLUSIONS: Our results suggest potential benefits of PUFA consumption on mortality which are only apparent in the absence of statin therapy. It seems prudent to consider the potential benefit of PUFA consumption in the primary prevention of CVD among patients who are not candidates for statin therapy but are at increased risk for CVD and mortality.

2019 UK National Guideline for consultations requiring sexual history taking : Clinical Effectiveness Group British Association for Sexual Health and HIV.

This guideline is an update of a previous version published in 2013. In this new version, we have reflected changes in the way sexual health services are now provided by assuming an integrated Sexual Health/Sexual and Reproductive Healthcare service. There are new recommendations for online testing, female genital mutilation (FGM), chemsex and considerations for transgender (and non-binary) individuals. Previous versions rather assumed a cis-gender clientele and so we have taken a more mechanistic approach to sex and risk without assuming gender identification. We have updated our gender terminology in line with the British Association for Sexual Health and HIV 'sexual health standards for trans, including non-binary, people' although have retained the terminology of 'men' and 'women' in a few cases where it related to other guidelines, e.g. human papillomavirus vaccination and FGM.

Preferential synthesis of ferritin and albumin by different populations of liver polysomes.

Free polysomes and a mixture of free and membrane-attached polysomes were isolated separately from rat liver, and each was added to a cell-free, protein-synthesizing system. The free polysomes showed a greater capacity than the mixed polysome population for incorporation of (14)C-leucine into ferritin, whereas the reverse was true for (14)C-leucine incorporation into albumin.

L-dopa: disaggregation of brain polysomes and elevation of brain tryptophan.

One hour after administration of L-dopa (50 to 300 milligrams per kilogram), there is a marked disaggregation of brain polysomes in immature rats. Adult animals show a similar response, but require larger doses of the amino acid (500 milligrams per kilogram). Single doses of L-dopa significantly elevate amounts of tryptophan in the brain; hence their effect on polysomes does not result from the unavailability of this amino acid.

Dopamine: mediator of brain polysome disaggregation after L-dopa.

The disaggregation of brain polysomes which is produced by giving large doses of (L)-dopa to rats is not reproduced by administering its metabolite, 3-O-methyldopa, by giving D-dopa, which also depletes the brain of S-adenosylmethionine but is not converted to catecholamines, or by giving the L-dopa after a decarboxylase inhibitor. Polysome disaggregation is potentiated by the prior administration of a monoamine oxidase inhibitor, indicating that formation of a catecholamine is an obligatory requirement. These observations suggest that the mechanism by which L-dopa disaggregates brain polysomes involves its conversion to dopamine within the majority of brain cells.

Epidemiology of herpes simplex virus types 2 and 1 amongst men who have sex with men attending sexual health clinics in England and Wales: implications for HIV prevention and management.

The objective was to investigate herpes simplex virus (HSV) epidemiology amongst HIV-positive and HIV-negative men who have sex with men (MSM) in England and Wales. Unlinked anonymous sera from 3,968 MSM attending 12 sexual health clinics in 2003 were tested for HIV, HSV-2 and HSV-1 antibodies. Fifty-five percent of HIV-positive MSM were HSV-2-seropositive, compared to 17% of HIV-negative MSM (Adj RR: 2.14 [CI: 1.92-2.37]). Amongst HIV-positive individuals, there was no significant difference in HSV-2 seroprevalence by knowledge of HIV status or whether the HIV infection was recently acquired (determined through STARHS). HIV infection was also independently associated with HSV-1 serostatus (Adj RR 1.19 [CI: 1.14-1.24)]). Four of the twelve attendees who received a diagnosis of recurrent anogenital herpes at the clinic visit were HSV-1-seropositive but not HSV-2-seropositive at the time, although no cultures or PCR results were available to type the cause of the ano-genital presenting disease. It is of concern that one in two HIV-positive MSM and one in six HIV-negative MSM may be infected with HSV-2, given increasing evidence of its impact on HIV progression, onward transmission and acquisition. To date results have been disappointing from trials aimed at reducing HIV onward transmission and HIV acquisition using HSV antiviral medication. However, recent research in an African context demonstrates the efficacy of HSV antivirals in delaying HIV progression. The high prevalence of HSV-2 amongst HIV-positive MSM suggests that an increased focus on HSV control in the management of HIV amongst MSM in the United Kingdom may be warranted. Given this and existing research on the high prevalence of genitally acquired HSV-1 amongst MSM in the UK, further research is also warranted into the role of HSV-1 in the HIV epidemic in this context.

National study of HIV testing in men who have sex with men attending genitourinary clinics in the United Kingdom.

OBJECTIVES: To determine what proportion of men who have sex with men (MSM) attending genitourinary medicine (GUM) clinics are offered and accept an HIV test and to examine clinic and patient characteristics associated with offer and uptake. METHODS: A cross-sectional study of all GUM clinics in the United Kingdom, involving a case note review of up to 30 patient records per clinic and the completion of a clinic policy form. RESULTS: Overall, 86% of MSM were offered a test and of those 82% accepted a test. Attending with symptoms of a sexually transmitted infection (STI), fewer numbers of partners in the past three months and having tested previously were all independently associated with a decreased likelihood of being offered a test. Attending with symptoms of an STI, increasing age, never having had a risk from unprotected anal intercourse or a previous HIV test and increasing time to wait for results were all independently associated with a decreased likelihood of a patient accepting a test. Only a quarter of clinics reported a written policy for HIV testing intervals among MSM; however, all clinics reported offering testing to all new MSM patients at first screening. The testing policy for re-attending patients was less clear. CONCLUSIONS: Testing must reach those at most risk and those less likely to test in order to reduce further the proportion of undiagnosed HIV infection. This study suggests that opportunities to detect infection may be being missed and a move towards universal testing of all MSM attending with a new episode, as well as testing within the window period, is recommended.

Sex difference in distribution and iron responsiveness of the two ferritins of rat cardiac and skeletal muscle.

The presence of two electrophoretically and structurally distinguishable forms of ferritin ("fast" and "slow") in cardiac and skeletal muscle (diaphragm) of the rat was confirmed. Although the total amount of cardiac ferritin showed no difference in concentration in male and female rats, the distribution between the fast and slow species was markedly different in the two sexes, the fast form predominating in the cardiac muscle and diaphragm of the female. In agreement with this, the rates of synthesis and of degradation of the fast species were greater in the female, while the opposite obtained for the male. Iron administration stimulated synthesis of each ferritin species in the cardiac muscle and diaphragm of both sexes. Induction of cardiac connective tissue hypertrophy with isoproterenol inverted the ratio of slow to fast ferritin in female rats, while iron administration along with isoproterenol restored this to normal. It is concluded that the metabolism of ferritin in cardiac and skeletal muscle is sensitive both to sexual status and to iron administration.

RNA synthesis by villus and crypt cell nuclei of rat intestinal mucosa.

Rat intestinal mucosa was separated by eversion and vibration to provide a sequence of fractions from predominantly villus cells to predominantly crypt cells. The proportions of these cell types in each fraction were computed from the concentrations of alkaline phosphatase (villus cells) and thymidine kinase (crypt cells) in each population. The isolated mucosal fractions varied from about 90% villus cells to 90% crypt cells. Following injection of the rats with [3H]thymidine, the nuclei were isolated from each mucosal cell fraction and the amount of radioactivity incorporated into DNA was measured as an index of crypt cell abundance. The isolated nuclei were also incubated with ribonucleoside triphosphates and the amount of RNA synthesized was measured. Nuclei labeled with [3H]thymidine were found only in fractions rich in crypt cells, whereas capacity for RNA synthesis remained very active in mucosal fractions consisting predominantly of villus cells. It is concluded that non-dividing villus cells continue to make RNA.

Structural features of rat cardiac ferritins.

Ferritin extracted from rat heart containes two species separable by gel electrophoresis. These were purified and examined for structural characteristics. As in gel electrophoresis, cardiac ferritin preparations yielded only two bands on isoelectric focusing in gels, with pI values of 4.6 and 4.8. After separation by preparative electrophoresis, the two species were found to have a different amino acid composition from each another and from liver ferritin. Similarly, peptide maps showed several components not found in liver ferritin. On dissociation and electrophoresis with sodium dodecyl sulfate, heart ferritins were found to contain subunits of the same sizes as in other rat ferritins but also some larger components. Since cardiac ferritins have apparent molecular weights greater than those of other ferritins, it is concluded they probably contain more subunits, and possibly some of larger size not present in ferritins of other tissues.

Structural differences in ferritins from normal and malignant rat tissues.

Ferritins purified from several normal and malignant rat tissues were examined for amino acid composition, content of tryptic peptides, available sulfhydryl groups and subunit sizes and proportion. Ferritin extracted from adult kidney, neonatal liver and hepatic and renal tumors differed from the ferritin of adult rat liver in migration on electrophoretic gels and in antibody affinity, but did not differ among themselves. Nevertheless, they showed distinctive differences in amino acid composition and tryptic peptide content. All of them and also adult liver ferritin contained two major species of subunits differing in molecular weight. The proportions of subunits, and the available sulfhydryl groups of the intact ferritin molecules, differed among these tissue ferritins. On the basis of amino acid and peptide content, the ferritins of hepatomas and the renal tumor analyzed showec the greatest similarity but not identity. The ferritin of neonatal liver was next most similar. Kidney ferritin differed considerably in composition from tumor and neonatal ferritins, while adult liver ferritin was the most extremely divergent of the series examined. A similar progressive difference was found on examining the proportions of subunits and sulfhydryl groups in these ferritins. However, changes in subunit proportion cannot explain the amino acid and peptide compositional changes.

Ntau-methylhistidine content of mixed proteins in various rat tissues.

In order to use Ntau-methylhistidine (3-methylhistidine) excretion in the urine as a measure of muscle protein breakdown, it is necessary to demonstrate that other tissues are not important sources of this protein constituent. Accordingly, the concentration of Ntau-methylhistidine in blood serum and in the mixed proteins of heart, brain, lung, kidney, diaphragm, spleen, testis, stomach, liver and hind leg skeletal muscle was measured in male rats of approx. 400 g body weight. The free Ntau-methylhistidine concentration of rat serum was less than 2 nmol per ml. In contrast, measurable amounts of Ntau-methylhistidine were found in the mixed proteins of all tissues and organs examined. The highest concentration was found in skeletal muscle (658 nmol/g tissue). Assuming muscle mass to be 45% of body weight, it has been estimated that the muscle contains more than ten times the total amount of this amino acid present in all of the other organs analyzed, which together account for about 20% of total body weight. These findings indicate that skeletal muscle is likely to be the major source of urinary Ntau-methylhistidine and the latter is, in consequence, a reflection of myofibrillar protein breakdown in skeletal muscle.

Microheterogeneity of human placental lactogen showing different patterns in individuals.

Samples of human placental lactogen, obtained either as a standard pooled preparation or prepared from individual placentas, were shown to migrate as a single band on acrylamide gel electrophoresis. When subjected to isoelectric focusing in polyacrylamide gels, the pooled sample was resolved into bands at pI values 5.0, 5.5, 5.8. 6.0, 6.1 and 6.2. Different batches of the standard pooled sample gave different proportions of each isoprotein species. Isolation and refocusing of individual bands did not alter the pI of each. Treatment with urea or with p-chloromercuribenzoate did not eliminate microheterogeneity seen on isofucising, indicating that the observed heterogeneity is probably not due to conformational differences or to restriction of molecular shape of disulfide bonds. It was shown by immunodiffusion that all the isofocusing reacted similarly against a common antibody to human placental lactogen. When placental lactogen was extracted from individual full term human placentas, the same isoprotein bands were observed but their proportions varied markedly from one placenta to another, and not all bands were present. Thus human placental lactogen displays considerable microheterogeneity which varies with individual placentas.

Size and charge heterogeneity of rat tissue ferritins.

Ferritins purified from horse spleen and from rat liver, kidney, heart and hepatoma were analyzed by quantitative polyacrylamide gel electrophoresis. From the migration characteristics of these ferritins at several gel concentrations, Ferguson plots were constructed and the molecular sizes and charges (apparent valences) together with their statistical variability were obtained by applying Rodbard computer programs to the data. Finally, ellipses were drawn describing the 95% confidence limits of these data for size and charge and were used to identify those ferritins that differed in size and/or charge. By these criteria, many of the tissue ferritins were differentiated from one another in terms of their molecular size and/or charge. Among the various tissue ferritin monomers, the molecular sizes were essentially similar (420 000-490 000) except for the two heart ferritins which were larger (530 000 and 626 000, respectively). However, the estimated charges on rat liver, kidney and hepatoma monomers (30-38 net protons per molecule) differed from that of spleen monomer (51 net protons per molecule) while the larger rat heart ferritin also had a greater charge (83 net protons) than the smaller (40 net protons). Apoferritins prepared chemically by removal of iron from the holoferritins had migration properties indistinguishable from the parent holoferritins. The migration properties of minor (dimeric) ferritin bands on the gels were compared with those of the monomer bands. The molecular sizes of the minor bands were larger than those of the major bands, and were not inconsistent with a doubling in size. However, charge differences varied, being either similar for major and minor forms (spleen ferritin), approximately twice for the minor form (rat hepatoma ferritin) or five times greater for the minor form (rat liver ferritin). These differences in behavior were confirmed by using minimally sieving gels, on which the major bands of horse spleen ferritin failed to separate whereas those of rat liver ferritin were readily separable. It is concluded that dimers of ferritins from different tissues may associate in different ways.

Mechanism of D-amphetamine inhibition of protein synthesis.

At 1 h after intraperitoneal administration of D-amphetamine sulphate (15 mg/kg), rat brain polyribosomes show disaggregation accompanied by reduced capacity for in vitro peptide chain elongation. The direct action of amphetamine on cell-fine protein-synthesizing systems was therefore explored. When brain or liver polyribosomes from untreated rats were incubated with pH 5 enzyme, peptide chain elongation was not inhibited by the addition 4 mM amphetamine to the medium. On the other hand, an initiation-dependent system consisting of rat liver of brain mRNA and wheat germ S-30 fraction showed inhibition of [3H]leucine incorporation by 50% when 4 mM amphetamine were added. The metabolites of amphetamine, p-hydroxyamphetamine and p-hydroxynorephedrine, had no inhibitory action in either system, but the potent neurotoxin p-chloroamphetamine was a more powerful inhibitor of initiation than amphetamine. By using [3H]amphetamine, it was shown that amphetamine binds to the 80-S ribosomes of the wheat germ system. This binding depended on the presence in the system of natural liver or brain mRNA or several synthetic mRNAs, but was not promoted by polyuridylic acid as the messenger. Significantly, polyuridylic acid-dependent polyphenylalanine synthesis by the wheat germ system was not inhibited by amphetamine or p-chloroamphetamine. Therefore, it was concluded that amphetamine inhibits protein synthesis by interfering with initiation through a step related to formation of the mRNA ribosome complex.

Insulin-like growth factor receptors in rat placental membranes.

The nature and relative quantity of insulin-like growth factor (IGF) receptors in rat placental microsomal membranes was investigated by competitive binding studies and covalent cross-linking followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Binding studies revealed that 100 micrograms membrane protein specifically bound 26.5% of [125I]iodo-IGF-II, 19.6% of [125I]iodomultiplication-stimulating activity III-2 [( 125I]iodo-MSA-III-2), and 11.5% [125I]iodo-IGF-I. IGF-II was equipotent with MSA-III-2, and both were approximately twice as potent as IGF-I in competing with [125I]iodo-IGF-I for binding. In contrast, IGF-I competed for the binding of [125I]iodo-MSA and [125I]iodo-IGF-II with only 5-20% the potency of unlabeled MSA and IGF-II. Insulin competed weakly with [125I] iodo-IGF-I for binding (achieving half-maximal displacement at 20 micrograms/ml), but did not compete with [125I]iodo-MSA for binding. This evidence suggested that while IGF-I binds to both IGF-I and IGF-II receptors, the majority of IGF-I binding is due to an interaction with IGF-II receptors. Studies using [125I]iodo-IGF-I covalently cross-linked to placental membrane receptors followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirmed that molecular species characteristic of the subunits of IGF-I receptors are present in rat placenta. It is concluded that rat placenta, like human placenta, contains receptors for both types of IGFs. Unlike human placenta, the majority of the receptors are of the IGF-II type.

An autocrine/paracrine role for insulin-like growth factors in the regulation of human placental growth.

Tissue derived from preterm (9-19 weeks gestation) and term (38-41 weeks gestation) human placentae were examined for their ability to synthesize and secrete insulin-like growth factors (IGFs) in organ culture. IGF-I was measured by a specific RIA, and IGF-II by a rat placental membrane radioreceptor assay. First, explants of placental tissue were maintained in organ culture. These explants secreted immunoreactive IGF-I (IR-IGF-I). There were no differences in the IR-IGF-I content of media conditioned by term and preterm placentae under these conditions. The similarity of this material to authentic human IGF-I was supported by parallel displacement in a specific RIA and coelution during Sephadex G-50 gel filtration. Second, monolayer cultures of fibroblasts from normal human preterm placentae (15-19 weeks gestation) were established. Confluent monolayers of these fibroblasts secreted IR-IGF-I (3-10 pg/10(5) cells X 40 h). IR-IGF-I secretion was reversibly inhibited by 5.3 microM cycloheximide, suggesting that the IR-IGF-I was the result of de novo protein synthesis. IR-IGF-I secretion was stimulated 5-fold by platelet-derived growth factor (0.6 U/ml). The response of monolayers of placental fibroblasts to IGF-I also was tested. IGF-I stimulated alpha-[3H]aminoisobutyric acid transport in these fibroblasts, with half-maximal stimulation occurring at 2-3 ng/ml. Stimulation of alpha-[3H]aminoisobutyric acid uptake by IGF-I correlated with specific binding of [125I]iodo-IGF-I. Half-maximal inhibition of [125I]iodo-IGF-I binding occurred at 2-3 ng/ml IGF-I. Placental tissue also secreted IGF-II-like activity, as measured by radioreceptor assay. Media conditioned by placental explants contained 15-20 ng/mg protein X 48 h, and media conditioned by placental fibroblasts contained 3-7 ng/10(5) cells X 40 h IGF-II determined by radioreceptor assay. These data support the hypothesis that the human placenta produces IGFs (IGF-II and/or IGF-I) that act locally to regulate placental growth.