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Background: Exercise modality differentially alters body composition and physical performance. Metabolic changes underlying these outcomes can be tracked through assessment of circulating metabolites. Here, global responses to an acute bout of aerobic or anaerobic exercise were compared in the serum of male and female subjects using a discovery-based metabolomics platform., Methods: On separate days, 40 healthy, active participants completed 45 min of aerobic cycling or resistance exercise, and blood samples were collected at rest, immediately after (T1) and 1 hour post-exercise (T2) to examine the serum metabolomic landscape., Results: The two exercise metabolomes appeared more similar than different in this healthy cohort. Overall, metabolomic signatures of both exercise modalities were markedly altered from rest at T1, and returned toward baseline by T2. Metabolomic perturbations at T1 and the T1-T2 rate of recovery post-exercise were greater following aerobic cycling than resistance exercise. Shared signatures included elevations in purine metabolism, substrate catabolism and mobilization, and inflammatory signaling. Aerobic exercise resulted in greater substrate diversity and use of fatty acids, whereas resistance exercise displayed higher purine turnover and glycolytic flux., Discussion: Individual metabolite differences between conditions were seen in magnitude but not direction. Metabolomic signatures of the exercise responses appeared fairly robust across exercise modalities. An initial perturbation and subsequent shift toward recovery by an hour post-exercise defined the signature in our healthy cohort. The expedited recovery following aerobic cycling may be explained by globally elevated lipid metabolism., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

A DASH (dietary approaches to stop hypertension) dietary pattern rich in fruits and vegetables and low-fat dairy products with increased dietary protein provided primarily from plant protein sources decreases blood pressure. No studies, however, have evaluated the effects of a DASH-like diet with increased dietary protein from lean beef on blood pressure and vascular health. The aim of this study was to study the effect of DASH-like diets that provided different amounts of protein from lean beef (DASH 28 g beef per day; beef in an optimal lean diet (BOLD) 113 g beef per day; beef in an optimal lean diet plus additional protein (BOLD+) 153 g beef per day) on blood pressure, endothelial function and vascular reactivity versus a healthy American diet (HAD). Using a randomized, crossover study design, 36 normotensive participants (systolic blood pressure (SBP), 116 ± 3.6 mm Hg) were fed four isocaloric diets,: HAD (33% total fat, 12% saturated fatty acids (SFA), 17% protein (PRO), 20 g beef per day), DASH (27% total fat, 6% SFA, 18% PRO, 28 g beef per day), BOLD (28% total fat, 6% SFA, 19% PRO, 113 g beef per day) and BOLD+ (28% total fat, 6% SFA, 27% PRO, 153 g beef per day), for 5 weeks. SBP decreased (P<0.05) in subjects on the BOLD+ diet (111.4 ± 1.9 mm Hg) versus HAD (115.7 ± 1.9). There were no significant effects of the DASH and BOLD diets on SBP. Augmentation index (AI) was significantly reduced in participants on the BOLD diet (-4.1%). There were no significant effects of the dietary treatments on diastolic blood pressure or endothelial function (as measured by peripheral arterial tonometry). A moderate protein DASH-like diet including lean beef decreased SBP in normotensive individuals. The inclusion of lean beef in a heart healthy diet also reduced peripheral vascular constriction.

Quantification of MRS spectra is a challenging problem when a large baseline is present along with a low signal to noise ratio. This work investigates a robust fitting technique that yields accurate peak areas under these conditions. Using simulated long echo time (1)H MRS spectra with low signal to noise ratio and a large baseline component, both the accuracy and reliability of the fit in the frequency domain were greatly improved by reducing the number of fitted parameters and making full use of all the known information concerning the Voigt lineshape. Using an appropriate first order approximation to a popular approximation of the Voigt lineshape, a significant improvement in the estimate of the area of a known spectral peak was obtained with a corresponding reduction in the residual. Furthermore, this improved parameter choice resulted in a large reduction in the number of iterations of the least-squares fitting routine. On the other hand, making use of the known centre frequency differences of the component resonances gave negligible improvement. A wavelet filter was used to remove the baseline component. In addition to performing a Monte Carlo study, these fitting techniques were also applied to a set of 10 spectra acquired from healthy human volunteers. Again, the same reduced parameter model gave the lowest value for chi(2) in each case.

The present article presents an exploratory qualitative process evaluation study of 'Ambassador' participation in CityNet, an innovative information-communication technology-based (ICT) project that aims to build aspects of social capital and improve access to information and services among disadvantaged groups in Nottingham, UK. A purposive sample of 40 'Ambassadors' interviewees was gathered in three waves of data collection. The two emergent analytic themes highlighted how improvements in confidence, self-esteem and social networks produced via participation were mitigated by structural problems in devolving power within the project. This illustrates how concepts of power are important for understanding the process of health promotion interventions using new media.

Aim: To investigate the expression of p63 and cytokeratins throughout the course of producing a cultivated autograft of limbal epithelial cells., Methods: A 75 year old male with a severe alkali burn to his right eye received two cultivated autografts of limbal epithelial cells on amniotic membrane followed by a corneal allograft. Immunostaining for p63 and cytokeratins was performed during ex vivo expansion with 3T3 fibroblasts, following subcultivation on amniotic membrane, and on the excised corneal button., Results: Cultures grown in the presence of 3T3 fibroblasts or on amniotic membrane displayed positive staining for keratins 14 and 19, and p63, but poor staining for keratin 3 (K3). The excised corneal button possessed a stratified epithelium of K3 positive cells residing on amniotic membrane., Conclusions: Our results document for the first time the co-expression of cytokeratins 14 and 19 with p63 in a cultivated limbal graft. These data support the conclusion that cultivated grafts of limbal epithelium contain predominantly undifferentiated cells with the potential to regenerate a normal corneal epithelium.

Levosimendan, a pyridazinone-dinitrile derivative, is a calcium sensitiser with additional action on adenosine triphosphate (ATP)-sensitive potassium channels. It is used intravenously (IV) for the treatment of decompensated cardiac failure. At therapeutic doses, levosimendan exhibits enhanced contractility with no increase in oxygen demands. It also produces antistunning effects without increasing myocardial intracellular calcium concentrations or prolonging myocardial relaxation. Levosimendan also causes coronary and systemic vasodilation. In patients with decompensated congestive heart failure (CHF), IV levosimendan significantly reduced the incidence of worsening CHF or death. IV levosimendan significantly increased cardiac output or cardiac index and decreased filling pressure in the acute treatment of stable or decompensated CHF in large, double-blind, randomised trials and after cardiac surgery in smaller trials. Levosimendan is well tolerated, with the most common adverse events (headache, hypotension, nausea) being secondary to vasodilation. It has not been shown to be arrhythmogenic. Levosimendan has shown no clinically important pharmacokinetic interactions with captopril, felodipine, beta-blockers, digoxin, warfarin, isosorbide-5-mononitrate, carvedilol, alcohol (ethanol) or itraconazole.

Pioglitazone is an orally administered insulin sensitising thiazolidinedione agent that has been developed for the treatment of type 2 diabetes mellitus. Pioglitazone activates the nuclear peroxisome proliferator activated receptor-gamma (PPAR-gamma), which leads to the increased transcription of various proteins regulating glucose and lipid metabolism. These proteins amplify the post-receptor actions of insulin in the liver and peripheral tissues, which leads to improved glycaemic control with no increase in the endogenous secretion of insulin. In placebo-controlled clinical trials, monotherapy with pioglitazone 15 to 45 mg/day has been shown to decrease blood glycosylated haemoglobin (HbA1c) levels in patients with type 2 diabetes mellitus. The addition of pioglitazone 30 mg/day to preexisting therapy with metformin, or of pioglitazone 15 or 30 mg/day to sulphonylurea, insulin or voglibose therapy, has been shown to decrease HbA1c and fasting blood glucose levels significantly in patients with poorly controlled type 2 diabetes mellitus. Pioglitazone has also been associated with improvements in serum lipid profiles in randomised placebo-controlled clinical studies. The drug has been well tolerated by adult patients of all ages in clinical studies. Oedema has been reported with monotherapy, and pooled data have shown hypoglycaemia in 2 to 15% of patients after the addition of pioglitazone to sulphonylurea or insulin treatment. There have been no reports of hepatotoxicity.

Insulin glargine is an extended-action biosynthetic human insulin. It precipitates in the neutral environment of subcutaneous tissue and is thus gradually absorbed into the bloodstream. The addition of small amounts of zinc to the formulation further delays absorption. In small euglycaemic clamp studies, the onset of action of insulin glargine was shown to be later, the duration of action longer and the time-action profile flatter than that of Neutral Protamine Hagedorn (NPH) insulin in patients with type 1 diabetes mellitus and healthy volunteers. Four large clinical trials of up to 28 weeks' duration have shown that a single bedtime dose of insulin glargine, in combination with preprandial short-acting insulin, is as effective or more effective than once or twice daily NPH plus short-acting insulin in improving glycaemic control in patients with type 1 diabetes mellitus. In 3 large comparative trials, insulin glargine decreased glycosylated haemoglobin and/or fasting blood glucose levels to a similar extent to that seen with NPH insulin in patients with insulin-dependent or non-insulin-dependent type 2 diabetes mellitus, either as monotherapy or in combination with oral hypoglycaemic agents. Insulin glargine appears to be well tolerated. A lower incidence of hypoglycaemia, especially at night, was reported in most trials with insulin glargine when compared with NPH insulin.

Ganirelix is a synthetic third generation gonadotropin-releasing hormone (GnRH) antagonist that is administered via the subcutaneous route. The drug competitively blocks GnRH receptors in the anterior pituitary gland, preventing endogenous GnRH from inducing luteinising hormone (LH) and follicle stimulating hormone release. Ganirelix effectively inhibited LH surges during controlled ovarian stimulation in a large, multicentre clinical trial in women undergoing in vitro fertilisation. A vital pregnancy rate per embryo transfer of 40.3% was achieved at weeks 5 to 6 after treatment with the 0.25 mg/day dosage. Subcutaneous ganirelix has been generally well tolerated in clinical trials. The most common adverse events were local injection site events, asthenia, nausea, malaise, headache and fatigue.

Smoking among partners of non-smoking pregnant women has been linked to adverse pregnancy outcome, including low birthweight. Paternal smoking also increases the risk of infant respiratory infections and sudden infant death syndrome, irrespective of maternal smoking status. Furthermore, men's smoking habits are probably one of the strongest influences on the extent to which women are able to quit smoking in pregnancy and maintain cessation post birth. In four focus group discussions, male smokers whose partners were pregnant discussed their beliefs about passive smoking in pregnancy, the barriers they perceived to quitting in pregnancy and their preparedness to support maternal cessation. Men were largely unaware that their own smoking could pose a specific risk to the fetus, but when pregnant women are smokers, men believed their own smoking habits were unimportant. For men, barriers to quitting during their partners' pregnancy were: lack of understanding as to how passive smoking can affect the fetus, including a belief that the fetus is "protected" inside its mother; lack of motivation to quit early in pregnancy due to the baby not being "real"; and concern about stress-induced marital discord associated with cigarette withdrawal. These findings are discussed with regard to messages and strategies which may influence men to quit during their partners' pregnancy.

Objective: To evaluate outcomes of a sexual health promotion intervention to prevent transmission of sexually transmitted diseases (STD) including HIV among genitourinary medicine clinic attenders., Design: A randomized controlled trial using pre-test and post-test measurements after 4 months, with clinical follow-up at 18 months., Setting: A genitourinary medicine clinic in Nottingham, UK., Patients: A total of 492 patients were randomly assigned either to an individually focused counselling and skills training intervention, including written materials (n = 148), to receive written materials only (n = 162), or to usual clinic procedure (n = 182)., Intervention: Social learning theory provided the theoretical framework for the intervention, which was informed by previous research in this setting, and aimed to alter perception of risk for HIV infection, increase knowledge and attitudes to condoms, and increase condom use., Main Outcome Measures: The main outcomes of interest were self-reported condom use and behaviour change. Other outcomes of interest were knowledge and attitudes to condoms, and re-attendance at the clinic with a diagnosis of STD., Results: Intervention subjects were significantly more likely than controls to report carrying condoms when anticipating sexual intercourse with a new sexual partner (P < or = 0.05), and were more likely to perceive themselves at risk of HIV infection (P < or = 0.001). There were no significant effects of the intervention on levels of knowledge about correct condom use, attitudes to condoms, self-reported condom use or incidence of STD., Conclusions: The limited effectiveness of the intervention suggests that condom promotion should continue, but that additional investment in clinic-based health promotion is unlikely to result in consequent health gain.

Novel 4,4-bis(trifluoromethyl)imidazolines have been found to be the potent acyl-CoA cholesterol acyltransferase (ACAT) inhibitors. ACAT is responsible for cholesterol esterification in the intestine, liver, and the arterial wall. These novel imidazolines also inhibit cholesterol ester formation in the macrophage. Several compounds have shown potent serum cholesterol-lowering activity in several animal models. Para-substitution of the 2-phenyl is critical for in vitro and in vivo activity. The 4,4-bis(trifluoromethyl)imidazolines with a para-cyano group on 2-phenyl and a 4-alkylcyclohexyl amide as the side-chain at the 5-position possess the most potent inhibitory activity in this series. Based on biochemical studies, this series acts as a competitive inhibitor with respect to cholesterol binding at the enzyme, which distinguishes it from most of the ACAT inhibitors discovered to date. Preliminary biological studies supported by X-ray crystal structures, molecular modeling, and structure-activity relationship (SAR) studies suggest that this series may be a cholesterol mimic.

Acyl-CoA:cholesterol acyltransferase (ACAT) is the enzyme largely responsible for intracellular cholesterol esterification. A systemic inhibitor of ACAT is believed to be able to slow or even reverse the atherosclerotic process. Towards that goal, a series of cyclic sulfides, derived from the hetero-Diels-Alder reaction of thioaldehydes with 1,3-dienes, and bearing carboxamide substituents, were prepared and evaluated for in vitro (in several tissues and species) and ex vivo ACAT inhibition. Minor changes in subsequent structure were found to have a significant effect in optimization of the biological activity of this series of compounds.

The gene expression and enzyme kinetics of acyl coenzyme A:cholesterol acyltransferase (ACAT) were investigated in human monocytes, macrophages, and foam cells. Northern blot analysis using a 1.65-kb coding region of human ACAT cDNA as the probe showed that each of the cell types exhibited four mRNA transcripts. The levels of the 4.2- and 3.7-kb ACAT transcripts were three- and sixfold higher, respectively, in macrophages than monocytes. These transcripts were expressed at the same high levels after conversion of macrophages to foam cells. In contrast, the 6.3- and 4.4-kb transcripts for ACAT were expressed at a relatively constant level in all three cell types. The expression of mRNA for glyceraldehyde phosphate dehydrogenase, the control gene in this study, was also expressed at a constant level in each of the cell types. The increase in ACAT mRNA was accompanied by changes in the kinetic properties of the enzyme. Specifically, there was a 14-fold increase in Vmax and a 71% decrease in Km with respect to oleoyl coenzyme A. Although not definitive, the concomitant changes in mRNA and Vmax strongly suggest that the amount of ACAT protein increases upon conversion of monocytes to macrophages. The data show that ACAT in monocytes can be regulated by both substrate and gene expression.

This paper aims to begin to consider the evidence for AIDS as a disease of poverty. It seeks to describe the important influence of the social and economic context of HIV/AIDS and of those behaviours associated with HIV transmission, and argues for a shift in emphasis in the conceptualization of the 'problem of AIDS'. The relationship between poverty and AIDS is explored, particularly in relation to global economic development, urbanization, homelessness and the disintegration of neighbourhoods, migration and systems of labour and production. Examples of socially-driven community-based responses to the prevention and control of the HIV epidemic in diverse cultures are discussed and the need for new outcome measures for assessing community initiatives is proposed.

A cross-sectional interview survey of 103 HIV/AIDS and 100 oncology staff in nine treatment sites in London aimed to identify ways in which work stress affected domestic and social lives of such staff. In all staff one-third of those without long-term emotional relationships stated they felt their work formed a barrier to their being involved in that way. Most subjects reported spending a considerable amount of time discussing work with partners, and work-related subjects caused conflict for just under half of the total sample. Thirty-nine percent reported their partners complained regularly about their commitment to work, and one-quarter overall reported their relationship had suffered as a result of their work in HIV or oncology. Using tests of association comparing group responses to structured interview and standardized psychometric items, few differences were found overall between staff in HIV/AIDS and staff in oncology. HIV staff were more likely to be motivated to work through peer concern, and friends of HIV staff were more likely to be supportive of their working in such a field. On the other hand, families of oncology staff were more supportive of their work than were families of HIV staff HIV staff were more likely to have had a family member who had suffered from a chronic or life-threatening disease. HIV staff were less likely to avoid discussing their work socially. Suggestions for addressing the potentially corrosive impact of health care in these fields, based on these samples, are made.

Several investigators have reported that feeding a semi-synthetic diet of casein and dextrose to New Zealand White (NZW) rabbits will increase total serum cholesterol concentration, principally through an increase in the beta-lipoprotein fractions, thereby creating a useful model for atherosclerosis research. Although there is evidence to suggest that the dextrose/casein diet alters low-density lipoprotein receptor and bile acid clearance of cholesterol, the underlying mechanism is not completely understood. The effects of the diet on the overall physiology of the rabbit have received little attention. In this study feeding a diet of casein and dextrose of male NZW rabbits for 4 weeks resulted in changes in the serum lipid concentrations. During that time the rabbits fed the dextrose/casein diet gained less weight than did control rabbits. In the test diet rabbits, liver aspartate and alanine transaminase activities were increased from baseline values of 27 +/- 2 U/L and 89 +/- 9 U/L respectively to 112 +/- 21 U/L and 281 +/- 34 U/L respectively, then returned to the high end of the reference range. Necropsy findings included hepatomegaly caused by vacuolar hepatopathy in 19 or 20 experimental rabbits; rabbits fed the control diet had no hepatic lesions. Ultrastructural analysis revealed that enlargement of the liver cells was due to glycogen deposition. Adrenal glands from animals fed the experimental diet had a minimal change in the size of the adrenocortical cells consisting of slight ballooning and rarefaction of the cytoplasm. In a second study the level of dietary fiber was doubled. This resulted in a three-fold increase in lipid concentrations, compared with the fivefold increase in the first study. The liver enzyme activities were increased to the same extent as in the first study. Histologic changes were comparable to those in the first study. The activity of hepatic cholesterol 7alpha-hydroxylase was 3.7 +/- 0.4 pmol/min/mg of protein, compared with the control value of 7.7 +/- 1.1 pmol/min/mg of protein (P < 0.05) in the second study. The improved rate of weight gain and the lesser increase in total serum cholesterol concentration in the second study with increased dietary fiber suggest that two separate activities may be involved. Although the level of dietary fiber may be related to weight gain and total serum cholesterol values, the relation to the decrease in liver transaminase activities in study 1 was probably coincidental. It appears that the dextrose/casein diet causes decreased activity of hepatic cholesterol 7alpha-hydroxylase, which could cause a decrease in the biliary excretion of cholesterol.

This study was conducted to examine the interpatient variability in steady-state plasma concentrations of fluphenazine by repeat depot intramuscular administration, and to determine the relationship between these concentrations and clinical state. Steady-state pre-dose concentrations of fluphenazine in plasma were measured using a sensitive and specific gas chromatography/mass spectrometry (GC/MS) assay in 24 patients with schizophrenia who were receiving continuous treatment with depot intramuscular fluphenazine decanoate. Clinical response was measured using the Andreasen Scale for positive and negative symptoms. Steady-state plasma concentrations of fluphenazine ranged from undetectable (< 0.1 ng/ml) to 27.9 ng/ml, with a median of 0.5 ng/ml. No significant associations were found between plasma concentration and dosage, or age and sex of the patient. Steady-state plasma concentrations in patients taking anticholinergic agents were significantly higher than in patients not receiving such drugs (P < 0.05 by Mann-Whitney U-test). Poorer control, expressed as the sum of the negative symptom scores or the sum of the positive and negative symptom scores, was related to higher log transformed plasma concentration of fluphenazine and higher fluphenazine decanoate dosage. The log transformed plasma concentrations of fluphenazine and the fluphenazine decanoate dosages were weakly related. Patients receiving another antipsychotic drug in addition to fluphenazine decanoate tended to have poorer clinical control and higher dosages of fluphenazine decanoate. These results indicate the useful role that plasma level monitoring can fulfil in identifying patients who are therapy-resistant despite high plasma levels.

Acyl-CoA:cholesterol acyltransferase (ACAT) is the primary enzyme involved in intracellular cholesterol esterification. Arterial wall infiltration by macrophages and subsequent uncontrolled esterification of cholesterol leading to foam cell formation is believed to be an important process which leads to the development of fatty streaks. Inhibitors of the ACAT enzyme may retard this atherogenic process. We have recently discovered a series of imidazoles which are potent in vitro ACAT inhibitors in the J774 macrophage cell culture assay. This paper will describe the design, synthesis, and structure--activity relationship for this very potent series of compounds.

A series of 4,5-diaryl-2-(substituted thio)-1H-imidazoles has been synthesized and demonstrated to be potent inhibitors of acyl-CoA:cholesterol acyltransferase (ACAT). The design, synthesis, and structure-activity relationships for this series are reported herein. One of the compounds from this series, N'-(2,4-difluorophenyl)-N-[5-[(4,5-diaryl-1H-imidazol-2- yl)thio]pentyl]-N-heptylurea (DuP 128), was selected for development as an intestinally active ACAT inhibitor. DuP 128 is a potent ACAT inhibitor in vitro and in vivo, inhibiting ACAT in rat hepatic microsomes with an IC50 = 10 nM and possessing potent antihypercholesterolemic activity in vivo.

To test the hypothesis that hepatic cholesteryl ester is involved in the regulation of apolipoprotein (apo) B secretion into plasma, apoB kinetic studies were performed in six control miniature pigs and in six pigs after a 21-day administration of the acyl coenzyme A:cholesterol acyltransferase (ACAT) inhibitor DuP 128 (2.2 mg.kg-1.d-1 i.v.). Pigs were fed low-fat, cholesterol-free diets. Total plasma cholesterol, triglyceride, very-low-density lipoprotein (VLDL) triglyceride, and low-density lipoprotein (LDL) cholesterol decreased 18%, 29%, 40%, and 26% respectively (P < .03). 131I-VLDL and 125I-LDL were injected simultaneously into each animal, and apoB kinetics were analyzed by using multi-compartmental analysis (SAAM30). VLDL apoB pool size decreased significantly by 60% (0.32 versus 0.84 mg/kg), which was due to a 65% reduction in the VLDL apoB production or secretion rate (1.03 versus 2.94 mg.kg-1.h-1). The fractional catabolic rate was unchanged. LDL apoB pool size decreased nonsignificantly by 18% (5.61 versus 6.90 mg/kg) due entirely to a 24% decrease in production rate (0.26 versus 0.34 mg.kg-1.h-1). At necropsy, hepatic microsomal ACAT activity decreased by 68% (0.28 versus 0.88 nmol.min-1.mg-1; P < .0002). Although an increase in hepatic free cholesterol leading to a decreased LDL receptor expression might be expected, this did not occur. The concentration of hepatic cholesterol and the LDL apoB fractional catabolic rate were unaffected by DuP 128. In addition, the concentration of hepatic triglyceride and the activity of diacylglycerol acyltransferase were not altered by DuP 128, indicating a lack of effect of DuP 128 on hepatic triglyceride metabolism. We conclude that inhibition of hepatic cholesteryl ester synthesis in vivo decreases apoB secretion into plasma.

This paper describes the findings of a randomised controlled trial of the short-term impact of counseling in the general practice setting. Compared with patients who received usual advice from their general practitioner for acute problems such as relationship difficulties, anxiety and depression, those who received counseling from qualified counselors working within the primary health care context showed greater improvement in psychological health as measured by the General Health Questionnaire. Significantly fewer of those counselled were prescribed anti-depressant drugs by the general practitioners in the study, or were referred to psychiatrists or clinical psychologists for care. In addition those patients who attended sessions with the practice counselor were more likely to report that they were satisfied with their treatment and more expressed feelings of well-being.

Intestinal cholesterol esterification by the enzyme acyl-CoA:cholesterol acyltransferase (ACAT) is a presumed prerequisite for cholesterol absorption. We evaluated the effect of a potent, poorly absorbed ACAT inhibitor (DuP 128: N'-(2,4-difluorophenyl)-N-[5-(4,5-diphenyl-1H-imidazol-2-ylthio)pe ntyl]- N-heptylurea) on cholesterol absorption in a randomized trial. Thirty subjects received DuP 128 for 7 weeks, 10 each at 900 mg per day, 1800 mg per day, and 3600 mg per day; six subjects received placebo; and nine subjects received 1 gm neomycin twice a day. Cholesterol absorption determinations used a continuous dual isotope 14C-cholesterol and 3H-beta sitosterol method. DuP 128 (pooled doses) induced at 14.4% +/- 11.4% reduction in cholesterol absorption (p < 0.05 versus placebo): 17.6% +/- 8.4% at 900 mg, 9.1% +/- 11.4% at 1800 mg, and 17.1% +/- 12.9% at 3600 mg. Neomycin induced a 26.4% +/- 10.7% reduction (p < 0.01). After 6 weeks, neomycin reduced serum total and low-density lipoprotein cholesterol by 22.4% +/- 9.2% and 24.0% +/- 11.6%, respectively (p < 0.01 versus placebo). DuP 128 induced reductions of 3.9% +/- 11% (difference not significant) and 4.95% +/- 14.3% (p = 0.05). ACAT inhibitors limit cholesterol absorption in humans; however, the magnitude of the effect, as exemplified by DuP 128, is small.

Recommendations from official sources highlight a number of key principles which are essential for effective sex education within schools. These relate to the planning and teaching of the topic, in-service training of teachers, and the establishment of links between schools and parents. Models of practice in the teaching of sex education vary between schools throughout England; also the wide variations in quality and quantity of provision indicate considerable scope for improvement. Government, despite its key role in shaping provision of sex education in schools, does not appear to be consistently supportive. This paper examines and assesses the impact of a number of key policies, including those related to the 1993 Education Act, which will change the legal framework for the teaching of sex education within schools. It makes a series of practical recommendations for purchasers of health promotion services, with the intention of supporting and furthering the development of sex education in schools.

An anonymous self-completion questionnaire on smoking was completed by 2065 (60 per cent) 15-16-year-olds attending secondary schools in Doncaster in 1991. Almost one in four girls (23 per cent) and one in six boys (16 per cent) reported they were regular smokers, an overall increase of 8 per cent since a similar survey in 1988. An increase in smoking was recorded in 12 of the 14 schools which took part in both the 1988 and 1991 surveys. Differences in smoking prevalence were recorded between schools. School-based analysis is likely to be important for the development of effective local intervention. Possible reasons for the overall increase in smoking are discussed, and the need for concerted efforts to influence smoking regulation policy decisions is stressed.

Both plasma and whole blood concentrations of 4-hydroxy-2-nonenal (4HNE) were significantly elevated in a population (n = 6) of 2 year old Watanabe heritable hyperlipidemic rabbits relative to a population (n = 6) of New Zealand White rabbits. The plasma concentrations were 74 +/- 10 nmol/L for the Watanabe group and 47 +/- 6 nmol/L for the New Zealand White group. The whole blood concentrations were 364 +/- 55 nmol/L for the Watanabe group and 188 +/- 64 nmol/L for the New Zealand White group. These results indicate that 4HNE concentrations in blood can be elevated in individuals with atherosclerosis and demonstrate the potential link between the formation of 4HNE and the progression of atherosclerosis.

Although smoking prevalence among pregnant women is highest among those of lower socio-economic status, the factors associated with cessation in this high risk group are poorly documented. This paper reports on data from a survey of working class women in Nottingham and Coventry, who were interviewed 6 months after having delivered a baby. It compares the characteristics of the 32 women who quit smoking during their pregnancy and were still ex-smokers at the 6 month post-natal point, with 472 women who had continued to smoke during their pregnancy or had returned to smoking in the post-partum period. A logistic regression analysis revealed three variables that were independently associated with long term cessation-having previously quit for more than 1 week, having a non-smoking partner, and believing that the children of smokers are more likely to get infections. Among the most disadvantaged, an understanding of how close social ties and economic circumstances influence smoking behaviour is crucial, if we are to develop more effective smoking cessation intervention strategies for working class women.

A new medical image analysis system to quantify atherosclerosis in the lower abdominal aorta using magnetic resonance imaging is described. This medical image analysis and display system permits the quantification of the three-dimensional (3D) properties of the vessel wall and lumen cross-sectional area and volumes. Preliminary results of employing this medical image analysis capability on magnetic resonance images demonstrated a twofold increase in wall volume per unit vessel length, corresponding to intimal thickening, before luminal narrowing was detected. This work demonstrated the feasibility and usefulness of quantitatively evaluating the 3D properties of the vessel lumen and wall by using a combination of magnetic resonance imaging and image analysis. The demonstration that intimal wall thickening is observed in images before observable occlusion of the lumen can be expected to provide an important early indicator of the future development of atherosclerosis. Such capability will permit detailed and quantitative studies to assess the effectiveness of therapies, such as drug, exercise, and dietary regimens.

Study Objectives: To evaluate the impact of an AIDS education programme designed for young adults., Design: A randomised trial with a pre-post test design., Setting: Participants were drawn from six youth training centres in the city of Nottingham, England., Study Population: All trainees aged 16-19 years attending the six centres were included in the sample and centres were randomly allocated to experimental (n = 173) and control (n = 164) groups. The response rate to both questionnaires was high (71%)., Measurements and Main Results: Data on sexual behaviour, knowledge, and attitudes towards HIV/AIDS were obtained by confidential questionnaire. Two thirds of the sample were sexually active. There were no differences between groups at pre-test and no differences by sex. The experimental group had a significantly higher level of knowledge than the control group post-test. Significantly more experimental than control trainees knew post-test that HIV could be transmitted via anal sex and through broken skin. In addition, twice as many experimental (53%) as control trainees (25%; p < 0.001) were aware that a cure for AIDS was unlikely in the near future. There were no observed effects on sexual behaviour, intentions, or attitudes., Conclusions: The Streetwize UK educational programme had a significant impact on young adults' knowledge of HIV/AIDS transmission and prevention in the short term. If community based AIDS education is to do more than merely inform, however, resources must be made available for peer led interventions and skills training.

OBJECTIVES--To assess the knowledge, attitudes, and perceptions of risk of occupational HIV transmission in hospital in relation to existing guidelines. DESIGN--Cross sectional anonymous questionnaire survey of all occupational groups. SETTING--One large inner city teaching hospital. SUBJECTS--All 1530 staff working in the hospital in October 1991 and 22 managers. MAIN MEASURES--Knowledge of safe working practices and hospital guidelines; attitudes towards patients with AIDS; perception of risk of occupational transmission of HIV; availability of guidelines. RESULTS--The response rate in the questionnaire survey was 63% (958/1530). Although staff across all occupational groups knew of the potential risk of infection from needlestick injury (98%, 904/922), significantly more non-clinical staff (ambulance, catering, and domestic staff) than clinical staff (doctors, nurses, and paramedics) thought HIV could be transmitted by giving blood (38%, 153/404 v 12%, 40/346; chi 2 = 66.1 p < 0.001); one in ten clinical staff believed this. Except for midwives, half of staff in most occupational groups and 19% (17/91) of doctors and 22% (28/125) of nurses thought gloves should be worn in all contacts with people with AIDS. Most staff (62%, 593/958), including 38% (36/94) of doctors and 52% (67/128) of nurses thought patients should be routinely tested on admission, 17% of doctors and 19% of nurses thought they should be isolated in hospital. One in three staff perceived themselves at risk of HIV. Midwives, nurses, and theatre technicians were most aware of guidelines for safe working compared with only half of doctors, ambulance, and paramedical staff and no incinerator staff. CONCLUSIONS--Policy guidelines for safe working practices for patients with HIV infection and AIDS need to be disseminated across all occupational groups to reduce negative staff attitudes, improve knowledge of occupational transmission, establish an appropriate perception of risk, and create a supportive and caring hospital environment for people with HIV. IMPLICATIONS--Managers need to disseminate policy guidelines and information to all staff on an ongoing basis.

Perception of risk has been suggested as an important element of sexual behaviour change among people who engage in behaviours which place them at risk of HIV infection. A study of the relationship between perception of risk of HIV infection and risk-related sexual behaviours was conducted in a genitourinary medicine clinic. The sample comprised 767 patients attending over a 3-month period; data collection was by self-completed questionnaire. A total of 574 questionnaires were suitable for analysis, representing a response rate of 75%. The majority of people in the sample reported behaviours which increased their risk of HIV infection, but only 19% (n = 112) of the sample perceived themselves to be personally 'at risk', despite adequate knowledge of HIV transmission and methods of risk reduction. Significant differences between social class groups were found for knowledge scores, with highest scores among professionals and lowest among unemployed subjects (Kruskal Wallis test chi 2 = 24.6, P less than or equal to 0.001). Increasing age was significantly associated with better knowledge; significantly more young people aged 16-20 years who did not perceive themselves 'at risk' (64%), had lower knowledge scores than older people who did not perceive themselves 'at risk' (41%). Among heterosexuals who reported having sex with other people in addition to their regular partner, 79% did not perceive themselves as 'at risk' of HIV infection, and of these, 64% reported only infrequent condom use with casual sexual partners. Significantly more heterosexual men (67%) than women (44%) reported multiple sex partners.(ABSTRACT TRUNCATED AT 250 WORDS)

The quality of data collected by surveys of sexual behaviour may be subject to sources of error involving reliability, validity, and non-participation bias. A preliminary study of sexual behaviour, including perception of risk for HIV infection, knowledge of HIV transmission and attitudes towards AIDS, was conducted in a genitourinary medicine clinic. The sample comprised 767 patients attending clinic over a 3-month period; comparisons were made between different methods of data collection (questionnaires and interviews) and between responders and non-responders. High levels of agreement were found between questionnaire and interview. Some sexual behaviours were more frequently reported at interview. No significant differences were found between responders and non-responders to either questionnaire or interview.

The regulation of aortic ACAT by a cholesterol substrate pool (CSP) was investigated in a rabbit progression/regression model of dietary-induced atherosclerosis. ACAT activity increased 25-fold during the 10-week progression phase of the study. ACAT activity decreased 8-fold during the 24-week regression phase of the study, however, it was still 14-fold greater than in normal aortas. ACAT activity assayed in the absence vs. the presence of exogenous cholesterol was used as a qualitative measure of the amount of cholesterol in the CSP. The CSP was filled to 28% of capacity in normal aortas, this increased to 75% during the progression phase. By the end of the regression phase, the CSP was filled to 100% of capacity even though serum cholesterol levels had returned to normal. The data are discussed in terms of emerging concepts of intracellular cholesterol trafficking, ACAT inhibitors, and the types of atherosclerotic lesions which may be subject to amelioration by ACAT inhibitors.

This study considered the characteristics, sports and leisure involvement, and social relations of approximately 1000 15- to 16-year-old pupils categorized as "overweight," "underweight," or "average" in terms of ponderal index scores. Academic attainment, social class and physical education teachers' perceptions were also considered. While results showed that pupils with average physiques were superior to the other two groups in fitness, the main and consistent contrasts among groups revolved around teachers' perceptions, body image, and peer group involvement. Thus overweight and underweight adolescents appeared at some disadvantage in certain social and educational encounters.

Rats dosed dermally with 39 or 130 mg/kg/day hexafluoroacetone sesquihydrate (HFA) for 14 days developed moderate or severe testicular atrophy, respectively; rats dosed with 13 mg/kg/day HFA for 14 days did not. Histologic evaluation of the testes revealed that spermatids, followed by spermatocytes, were the germ cells most affected by HFA; spermatogonia and Sertoli cells appeared to be less vulnerable. Lipogenesis from [3H]acetate and[14C]glucose was investigated in vitro in testes from HFA-treated and pair-fed control rats. Triacylglycerol and phospholipid synthesis was increased whereas sterol synthesis was decreased in testes from HFA-treated rats. Vitamin A and zinc were measured in the testes of control and HFA-treated rats; no differences in the levels of these nutrients were observed between the two groups. The data support the hypothesis that altered lipid metabolism, in particular sterol metabolism, is associated with the development of HFA-induced testicular atrophy.

This paper describes a longitudinal questionnaire study of the future hopes and worries of 547, 11- and 14-year-olds from Nottingham, England. Results from interviews with 152 of the 14-year-olds are also presented. More than half of the teenagers spontaneously expressed hopes for and worries about employment and unemployment. One third of adolescents, and more boys than girls, were concerned about war, including nuclear war. Proportions of pupils worried about unemployment, own mortality, lack of money and AIDS increased significantly with age. Interview and questionnaire findings were in general agreement. However, worries such as exam failure, childbirth and unhappy marriage were more prominent at interview and mentioned significantly more frequently by girls than boys. Worries about employment and nuclear war appear to predominate throughout adolescence, but are not the sole concern of this age group. Consideration should be given to discussing teenage worries in the context of school/family based educational ventures.

In the largest survey of smoking in pregnancy to date in the United Kingdom, 3882 women attending the two antenatal clinics in Nottingham during July and August 1986, were asked about their smoking habits. Thirty-seven per cent of pregnant women were smoking and only one in four of these was successful at stopping at some point during pregnancy. However, 55 per cent of the mothers who smoked at the start of pregnancy claimed to smoke less during pregnancy. No change was reported in the habits of one-quarter of the mothers who smoked during pregnancy and this proportion may represent an 'irreducible minimum'. Mothers were more likely to continue to smoke if younger (14-20 years), single, living with a partner who smoked, who left school at 16 years and were from manual working families. Those who succeeded in giving up smoking during pregnancy were more likely to be from professional and managerial families. Antenatal booklets about the dangers of smoking were the source of information cited most frequently. Half of the smoking mothers claimed not to have received advice from their family practitioners about the hazards of smoking nor information about how to give up the habit. Even fewer received such advice from hospital doctors, or midwives. This represents a major challenge to professional training in health education.

The hypothesis was examined that arterial microsomal membrane fluidity is decreased in atherosclerosis. To investigate this hypothesis, the fluorescence anisotropy (r) of 1,6-diphenylhexa-1,3,5-triene was measured in aortic microsomes isolated from normal and atherosclerotic rabbits. A decrease in membrane fluidity, as indicated by a significant increase in r, was observed in microsomes from atherosclerotic rabbits. Notably, the increase in r occurred prior to macroscopic lesion development. The data support the hypothesis that membrane fluidity is decreased in atherosclerosis and indicate that this decrease occurs early in the atherogenic process. The hypothesis that decreased microsomal membrane fluidity contributes to the increased activity of acyl-CoA:cholesterol acyltransferase (ACAT) in atherosclerosis was also investigated. The hypothesis was rejected on the basis that enrichment of microsomes from normal rabbits with exogenous cholesterol to achieve r values equal to that of microsomes from atherosclerotic rabbits did not result in comparable ACAT activity.

The ability of lanthanum chloride (LaCl3) to retard the progression of established atherosclerosis was investigated in cholesterol-fed rabbits. Rabbits were initially maintained on a high-fat plus cholesterol-supplemented diet for 10 weeks to induce lesions and were then changed to a low-fat diet or a low-fat diet supplemented with LaCl3 for an additional 24 weeks to permit their serum cholesterol levels to normalize. LaCl3 did not affect the rate at which serum cholesterol levels returned to normal. The dose of LaCl3 was approximately 30 mg/kg body weight/day. In comparison with controls, LaCl3-treated rabbits exhibited histologically less severe coronary artery and mitral valve atherosclerosis. Lesion severity in the carotid arteries was unaffected by LaCl3 treatment. Although statistically significant, the salutary effects of LaCl3 were relatively small. The data support the hypothesis that calcium antagonists can retard the progression of established atherosclerotic lesions. The data also illustrate the value of the mitral valve as a site to assess treatment effects on monocyte/macrophages in vivo.

A new substrate optimized assay for acyl-CoA:cholesterol acyltransferase (ACAT) was developed that permits the accurate measurement of ACAT activity in normal arterial microsomes. The apparent Km and Vmax of ACAT with respect to oleoyl-CoA were determined to be 3 microM and 17.7 pmole min-1 mg-1. While the Km value is similar to other values reported in the literature, the Vmax is 5- to 8-fold higher. The higher Vmax is attributable to the saturation of ACAT with not only oleoyl-CoA, but also cholesterol. The observation that exogenous cholesterol was necessary for the determination of maximal ACAT activity indicates that under normal conditions the endogenous level of microsomal cholesterol does not saturate ACAT. Assay of ACAT in the presence and absence of exogenous cholesterol permits a qualitative assessment of the amount of cholesterol in the cholesterol substrate pool of ACAT. Using this approach, it was found that hypercholesterolemia results in the expansion of the cholesterol substrate pool of ACAT. Of the 21-fold increase in ACAT activity in atherosclerotic aortas observed in this study. 80% of the increase was attributable to expansion of the cholesterol substrate pool, while 20% was attributable to more enzyme. Notably, the increase in the amount of ACAT was observed after only 2 weeks of hypercholesterolemia.

Alterations in lipid metabolism and cellular morphology in the liver were examined in female rats treated with 100 mg Ethmozine/kg/day for 7 days. The incorporation of either [3H]acetate with [methyl-14C]choline, or [methyl-14C]methionine was used to monitor the effect of the drug on neutral and phospholipid syntheses. Ethmozine (ETH) reduced the incorporation of choline into phosphatidylcholine (PC) by 50%, but the transmethylation of phosphatidylethanolamine to form PC was unaffected. The formation of lyso-PC was reduced by one-half irrespective of the donor radiolabel. An accumulation of both micro- and macrovesicles (fat) was found in the centri- and midlobular zones of the liver, which is likely the result of increased synthesis and decreased secretion of triacylglycerol (TAG). Incorporation of acetate into TAG was increased fivefold by ETH treatment, and to a lesser degree into cholesterol and cholesterylester/squalene.