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Biomedical subjects

R A Anderson

Publications and source records attributed to R A Anderson.

At least 73 records · Page 4Linked to original sources
PubMed2000

Ciprofibrate therapy improves endothelial function and reduces postprandial lipemia and oxidative stress in type 2 diabetes mellitus.

BACKGROUND: Exaggerated postprandial lipemia (PPL) is a factor in atherogenesis, involving endothelial dysfunction and enhanced oxidative stress. We examined the effect of ciprofibrate therapy on these parameters in type 2 diabetes mellitus. METHODS AND RESULTS: Twenty patients entered a 3-month, double-blind, placebo-controlled study. Each subject was studied fasting and after a fatty meal, at baseline, and after 3 months of treatment. Glucose and lipid profiles were measured over an 8-hour postprandial period. Endothelial function (flow-mediated endothelium-dependent vasodilatation [FMD]) and oxidative stress (electron paramagnetic resonance spectroscopy) were measured after fasting and 4 hours postprandially. At baseline, both groups exhibited similar PPL and deterioration in endothelial function. After ciprofibrate, fasting and postprandial FMD values were significantly higher (from 3.8+/-1. 8% and 1.8+/-1.3% to 4.8+/-1.1% and 3.4+/-1.1%; P<0.05). This was mirrored by a fall in fasting and postprandial triglycerides (3. 1+/-2.1 and 6.6+/-4.1 mmol/L to 1.5+/-0.8 and 2.8+/-1.3 mmol/L, P<0. 05). Fasting and postprandial HDL cholesterol was also elevated (0. 9+/-0.1 and 0.8+/-0.1 mmol/L and 1.2+/-0.2 and 1.2+/-0.1 mmol/L, P<0. 05). There were no changes in total or LDL cholesterol. Fasting and postprandial triglyceride enrichment of all lipoproteins was attenuated, with cholesterol depletion of VLDL and enrichment of HDL. There were similar postprandial increases in oxidative stress in both groups at baseline, which was significantly attenuated by ciprofibrate (0.3+/-0.6 versus 1.5+/-1.1 U, P<0.05). CONCLUSIONS: This study demonstrates that fibrate therapy improves fasting and postprandial endothelial function in type 2 diabetes. Attenuation of PPL and the associated oxidative stress, with increased HDL cholesterol levels, may be important.

Adult↗
PubMed2000

Endothelium-derived nitric oxide contributes to the regulation of venous tone in humans.

BACKGROUND: Although nitric oxide (NO) is known to play an important part in the regulation of arterial tone, little is known about its role in veins. The aim of this study was to investigate the role of basal and stimulated NO activity in the regulation of tone of the human venous capacitance bed. METHODS AND RESULTS: We measured venous tone using radionuclide forearm venous plethysmography in 24 healthy subjects with no cardiovascular risk factors. In 13 subjects, basal NO activity was assessed by measuring the effects on venous tone of an intra-arterial infusion of the NO synthase inhibitor N-monomethyl-L-arginine (L-NMMA). In the remaining 11 subjects, stimulated NO activity was evaluated by measuring the effects of an intra-arterial infusion of incremental doses of carbachol, followed in a subgroup by coinfusion with L-NMMA. Infusion of carbachol caused dose-dependent venodilation, with a maximal reduction in forearm venous tone of 40.1+/-12.5% (P<0.0001). Carbachol-induced venodilation was inhibited by L-NMMA (48.9+/-6.2% reversal of maximal venodilation, P<0.01). Infusion of L-NMMA alone caused venoconstriction (9.1+/-6.4% increase in venous tone, P=0.002). CONCLUSIONS: Human forearm capacitance veins exhibit both stimulated and basal NO activity, which indicates that NO contributes not only to the regulation of venous tone but also to resting venous tone in healthy human subjects.

Adult↗
PubMed2000

The activation loop of phosphatidylinositol phosphate kinases determines signaling specificity.

Phosphatidylinositol-4,5-bisphosphate plays a pivotal role in the regulation of cell proliferation and survival, cytoskeletal reorganization, and membrane trafficking. However, little is known about the temporal and spatial regulation of its synthesis. Higher eukaryotic cells have the potential to use two distinct pathways for the generation of phosphatidylinositol-4,5-bisphosphate. These pathways require two classes of phosphatidylinositol phosphate kinases, termed type I and type II PIP kinases. While highly related by sequence, these kinases localize to different subcellular compartments, phosphorylate distinct substrates, and are functionally nonredundant. Here, we show that a 20- to 25-amino acid loop spanning the catalytic site, termed the activation loop, determines both enzymatic specificity and subcellular targeting of PIP kinases. Therefore, the activation loop controls signaling specificity and PIP kinase function at multiple levels.

Amino Acid Sequence↗
PubMed2000

Plasmodium falciparum sporozoites increase feeding-associated mortality of their mosquito hosts Anopheles gambiae s.l.

There is some evidence that pathology induced by heavy malaria infections (many oocysts) increases mortality of infected mosquitoes. However, there is little or no published evidence that documented changes in feeding behaviour associated with malaria infection also contribute to higher mortality of infected mosquitoes relative to uninfected individuals. We show here for the first time that, in a natural situation, infection by the sporozoites of the malaria parasite Plasmodium falciparum significantly reduced survival of blood-feeding Anopheles gambiae, the major vector of malaria in sub-Saharan Africa. To estimate feeding-associated mortality of infected mosquitoes, we compared the percentage of sporozoite infection in host-seeking mosquitoes caught before and after feeding. The infection rate was 12% for mosquitoes caught during the night as they were entering a tent to feed; however, only 7.5% of the surviving members of the same cohort caught after they had had the opportunity to feed were infected. Thus, Plasmodium falciparum sporozoites increased the probability of dying during the night-time feeding period by 37.5%. The increase in mortality was probably due to decreased efficiency in obtaining blood and by increased feeding activity of the sporozoite-infected mosquitoes that elicited a greater degree of defensive behaviour of hosts under attack.

Animals↗
PubMed2000

Insulin-like biological activity of culinary and medicinal plant aqueous extracts in vitro.

To evaluate the possible effects on insulin function, 49 herb, spice, and medicinal plant extracts were tested in the insulin-dependent utilization of glucose using a rat epididymal adipocyte assay. Cinnamon was the most bioactive product followed by witch hazel, green and black teas, allspice, bay leaves, nutmeg, cloves, mushrooms, and brewer's yeast. The glucose oxidation enhancing bioactivity was lost from cinnamon, tea, witch hazel, cloves, bay leaf and allspice by poly(vinylpyrrolidone) (PVP) treatment, indicating that the active phytochemicals are likely to be phenolic in nature. The activity of sage, mushrooms, and brewers's yeast was not removed by PVP. Some products such as Korean ginseng, flaxseed meal, and basil have been reported to be effective antidiabetic agents; however, they were only marginally active in our assay. Our technique measures direct stimulation of cellular glucose metabolism, so it may be that the active phytochemicals in these plants improve glucose metabolism via other mechanisms or that this in vitro screening is not a reliable predictor of hypoglycemic effects in vivo for some products. In summary, the positive effects of specific plant extracts on insulin activity suggest a possible role of these plants in improving glucose and insulin metabolism.

Adipocytes↗
PubMed2000

Regulation of inhibin production in the human male and its clinical applications.

Investigation of the regulation of testicular function has been enhanced by the ability to measure the dimeric, biologically active form of inhibin in men, inhibin B. This has allowed the demonstration that inhibin B is the afferent arm of the feedback loop from the testis that regulates FSH secretion, and investigation of inhibin B levels during reproductive development and in a variety of physiological and pathological states. Such studies have demonstrated many primary aspects of the relationship between FSH, testicular function (and in particular spermatogenesis) and inhibin B levels in blood, though many more specific questions remain. These include the precise nature of the relationship between inhibin B secretion and Sertoli cell function and how this relationship is influenced by the germ cell types present in the testis and by overall sperm production. When such information becomes available it will allow more accurate interpretation of blood concentrations of inhibin B. Similarly, apical secretion of inhibin B into seminal plasma may have considerable value in aiding assessment of the status of the seminiferous epithelium. Finally, neonatal secretion of inhibin B as a measure of Sertoli cell number and/or as a predictor of adult reproductive function offers novel possibilities for assessment and intervention.

Adult↗
PubMed2000

Poly(sodium 4-styrene sulfonate): an effective candidate topical antimicrobial for the prevention of sexually transmitted diseases.

Presently marketed vaginal barrier agents are cytotoxic and damage the vaginal epithelium and natural vaginal flora with frequent use. Novel noncytotoxic agents are needed to protect women from sexually transmitted diseases. One candidate compound is a high-molecular-mass form of soluble poly(sodium 4-styrene sulfonate) (T-PSS). The antimicrobial activity of T-PSS was evaluated in primary culture systems and in a genital herpes murine model. Results obtained indicate that T-PSS is highly effective against herpes simplex viruses, Neisseria gonorrhoeae, and Chlamydia trachomatis in vitro. A 5% T-PSS gel protected 15 of 16 mice from vaginal herpes, compared with 2 of 16 mice treated with a placebo gel. Moreover, T-PSS exhibited little or no cytotoxicity and has an excellent selectivity index. T-PSS is an excellent candidate topical antimicrobial that blocks adherence of herpes simplex virus at low concentrations, inactivates virus at higher concentrations, and exhibits a broad spectrum of antimicrobial activity.

Animals↗
PubMed2000

ACAT1 and ACAT2 membrane topology segregates a serine residue essential for activity to opposite sides of the endoplasmic reticulum membrane.

A second form of the enzyme acyl-CoA:cholesterol acyltransferase, ACAT2, has been identified. To explore the hypothesis that the two ACAT enzymes have separate functions, the membrane topologies of ACAT1 and ACAT2 were examined. A glycosylation reporter and FLAG epitope tag sequence was appended to a series of ACAT cDNAs truncated after each predicted transmembrane domain. Fusion constructs were assembled into microsomal membranes, in vitro, and topologies were determined based on glycosylation site use and accessibility to exogenous protease. The accessibility of the C-terminal FLAG epitope in constructs was determined by immunofluorescence microscopy of permeabilized transfected cells. Both ACAT1 and ACAT2 span the membrane five times with their N termini in the cytosol and C termini in the ER lumen. The fourth transmembrane domain is located in a different region for each protein, placing the putative active site ACAT1 serine (Ser(269)) in the cytosol and the analogous residue in ACAT2 (Ser(249)) in the ER lumen. Mutation of these serines inactivated the ACAT enzymes. The outcome is consistent with the hypothesis that cholesterol ester formation by ACAT2 may be coupled to lipoprotein particle assembly and secretion, whereas ACAT1 may function primarily to maintain the balance of free and esterified cholesterol intracellularly.

Animals↗
PubMed2000

Potential impact of hormonal male contraception: cross-cultural implications for development of novel preparations.

The prospect of a hormonal male contraceptive is no longer distant. Data on the potential impact of this improvement in contraceptive provision, however, is limited, particularly between different cultures. We have therefore carried out a multi-centre study to assess men's attitudes to proposed novel hormonal methods. Questionnaire-based structured interviews were administered to men in Edinburgh, Cape Town, Shanghai and Hong Kong. Approximately 450 men were interviewed in Edinburgh, Shanghai and Hong Kong, and a slightly larger group (n = 493) in Cape Town to give samples (n > 150) of black, coloured and white men. Knowledge of existing male and female methods of contraception was high in all centres and groups. The majority of men welcomed a new hormonal method of contraception, 44-83% stating that they would use a male contraceptive pill. Overall, a pill was more acceptable than an injectable form (most popularly given at 3-6 month intervals); long-acting implants were least so except in Shanghai. Familiarity with comparable female methods appeared to influence acceptability, for both oral and injectable methods. Hong Kong was the only centre where a male method (condom) was currently the most commonly used; men there appeared to rate the convenience of condoms highly while being least likely to think that they provided effective protection against pregnancy compared to other centres, and were least enthusiastic about novel male methods. The acceptability of potential male hormonal methods of contraception was high in some groups but showed wide variability, determining factors including cultural background and current contraceptive usage. These results suggest that the emerging emphasis that men should have greater involvement in family planning will be substantiated when appropriate contraceptive methods become available.

Adolescent↗
PubMed2000

Would women trust their partners to use a male pill?

Despite a renewed interest in the development of hormonal contraceptives for men, many discussions about the potential acceptability of a 'male pill' end by speculating whether women would trust their partners to use the method reliably. To determine the views of women, we undertook a survey of 1894 women attending family planning clinics in Scotland (450), China (900) and South Africa (544). In all centres over 65% of women thought that the responsibility for contraception falls too much on women. More than 90% in South Africa and Scotland thought that a 'male pill' was a good idea, with Chinese women (71% in Hong Kong and 87% in Shanghai) only slightly less positive. Only 13% of the total sample did not think that hormonal male contraception was a good idea and only 36 women (2% of the total) said that they would not trust their partner to use it. 78% of Scottish women, 71% of Shanghai women, and 78% of white women and 40% of black and coloured women in Cape Town thought that they would use the method. This survey should dispel the myth that women would not trust their partners to use a 'male pill' reliably and illustrates the potential market for the method.

Adolescent↗
PubMed2000

Dose-finding study of oral desogestrel with testosterone pellets for suppression of the pituitary-testicular axis in normal men.

Prototype hormonal male contraceptive regimens generally achieve only incomplete suppression to azoospermia with potentially adverse metabolic effects. We have carried out a short-term dose-finding study to investigate the potential of an oral gestogen, desogestrel, with testosterone pellets. Normal men received a single dose of 300 mg testosterone with 75 microg, 150 microg or 300 microg desogestrel daily for 8 weeks (n = 10 per group). LH and FSH were rapidly suppressed, with little difference between groups. Testosterone concentrations fell slightly during treatment with evidence of a linear dosage effect. Plasma inhibin B showed minor changes, but in seminal plasma it was suppressed, becoming undetectable in all men in the 300 microg desogestrel group. There were no significant changes in lipoproteins, fibrinogen or sexual behaviour during treatment, and minor falls in haematocrit and haemoglobin concentration. Sperm concentration fell in a dose-dependent manner, with three men, one man and seven men in the three groups respectively achieving severe oligozoospermia (<3 x 10(6)/ml), and three men achieving azoospermia in the 300 microg group despite the short duration of the study. The combination of oral desogestrel with depot testosterone thus results in profound suppression of gonadotrophin secretion without adverse metabolic or behavioural effects. Desogestrel with a long-acting testosterone preparation is a promising approach to hormonal male contraception.

Administration, Oral↗
PubMed2000

The analysis of methadone in nail clippings from patients in a methadone-maintenance program.

This study offers an analytical scheme for methadone in fingernail clippings. Nail specimens (0.18-16.33 mg) were collected from 30 consenting adults participating in a methadone-maintenance program along with questionnaires regarding their drug-use histories. The nail clippings were stored in plastic bags and transferred to the laboratory for analysis. They were decontaminated by sonication for 15-min intervals successively in 0.1% sodium dodecyl sulfate, water (three times), and methanol (three times). The methanolic washes were collected and screened for methadone by enzyme immunoassay (EIA). Three washes were found sufficient to provide EIA negative results. The decontaminated nail clippings were hydrolyzed in 1M NaOH. Aliquots of the hydrolysates were screened for methadone by EIA and confirmed by gas chromatography-mass spectrometry (GC-MS). The mean methadone concentrations in fingernail clippings determined by EIA and GC-MS were 32.8 and 26.9 ng/mg, respectively. Hydrolysates of the equivalent of 10 mg of blank nail clippings were spiked with known concentrations of methadone and analyzed by the developed procedures in order to determine extraction recoveries and limits of detection of the two techniques. Based on our results, fingernails appear to be a potentially useful biological specimen for the analysis of methadone and the monitoring of patient compliance to methadone-maintenance programs.

Adult↗
PubMed2000

Differential expression of estrogen receptor-alpha and -beta and androgen receptor in the ovaries of marmosets and humans.

Estrogens and androgens are essential for the maturation of the ovarian follicle and normal fertility in the female. We have used antibodies specific for both forms of estrogen receptor (alpha [ERalpha] and beta [ERbeta]) and androgen receptor (AR) to investigate the pattern of receptor expression in ovaries obtained from women and from a New World primate, the Common marmoset (Callthrix jacchus). On Western blots, three antibodies directed against different peptides within human ERbeta all recognized recombinant human (h) ERbeta but did not bind to recombinant hERalpha. The ERbeta protein was extracted from human ovary and prostate and marmoset ovary. In marmoset and human ovaries, ERbeta protein was detected in the nuclei of granulosa cells in all sizes of follicle (both before and after formation of the antrum), and it was also detected in thecal cells, corpora lutea, surface epithelium, and stroma. In contrast, ERalpha protein was not detected in the nuclei of granulosa cells in preantral follicles, was low/absent from stromal and thecal cells, but was expressed in granulosa cells of antral follicles and in the surface epithelium. The pattern of expression of AR protein more closely resembled that of ERbeta than ERalpha. In conclusion, three independent antibodies have demonstrated convincingly that ERbeta is expressed in a wide range of cells in the primate ovary. Granulosa cells in preantral follicles could contain ERbeta:beta dimers. In antral follicles, however, ERalpha is also expressed, and the formation of homo- or heterodimers containing ERalpha may influence the pattern of gene activation within these cells.

Amino Acid Sequence↗
PubMed2000

Managing health care organizations: where professionalism meets complexity science.

This article examines the intersection of professionalism and complexity science as a source of new insights for improving the health care industry from both a clinical and business point of view. Viewing health care organizations as professional complex adaptive systems suggests eight leadership tasks for addressing the circumstances that engulf health care. Managers who adopt this view will be able to create new levers for positive movement in their organizations.

Commerce↗
PubMed2000

Hormonal contraception in the male.

The hormonal approach to male contraception is based on the suppression of gonadotrophin secretion with secondary suppression of spermatogenesis. This can be achieved by administration of testosterone or other androgen alone, but combined administration with a progestogen or GnRH analogue allows the dose of testosterone to be reduced to physiological replacement doses. This approach has been investigated for many years but without identification of a regimen which results in sufficient suppression of spermatogenesis to provide ensured contraception in all men, safely and conveniently. The reasons for this are discussed, and recent developments towards a regimen that fulfills all these criteria are described. Crucial to development of any new product is that it will be used: surveys of both men and women indicate firmly positive attitudes towards a 'male pill'. There are, therefore, grounds for cautious optimism that the next decade may see the introduction of the first novel male contraceptive for several hundred years.

Acne Vulgaris↗