Abstinence or controlled drinking?
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Alcohol Drinking↗
Biomedical subjects
L M Wilson
Publications and source records attributed to L M Wilson.
Stationary red blood cells induce a negative charge on mucosal capillary endothelium.
Previous studies on Wistar-Furth rat intestinal mucosal capillaries show a variation in extent of binding of cationized ferritin (CF) to the endothelial surface. Three possible causes of this variation were investigated: 1) location of capillaries along the intestine, 2) time after feeding, and 3) effect of short-term hemostasis. In studies 1 (5 rats) and 2 (22 rats), the intestinal circulation was perfused with CF and perfusion fixed for electron microscopy. Observation of capillaries demonstrated that variation in CF binding could not be explained by factors 1 or 2. In study 3, capillaries on the mucosal surface were viewed using epifluorescent microscopy and were perfused with fluorescein isothiocyanate (FITC)-labeled CF. Initial perfusion produced no binding, but perfusion after 2 or 10 min of stasis gave extensive binding (19 rats). Stasis with red blood cells in saline (6 rats) or with hemoglobin solution (6 rats) gave similar results, but stasis with saline, platelet-rich plasma, or red cell ghosts in saline did not produce binding (8, 7, and 5 rats, respectively). Hemoglobin injected into the circulation without stasis also caused binding of FITC-CF, but not if the nitric oxide (NO) donor, SIN-1, was injected simultaneously. Stasis with saline containing the NO inhibitor, NG-nitro-L-arginine methyl ester produced some binding of FITC-CF (5 rats). We conclude that intestinal mucosal capillaries do not express a net negative surface charge under brisk flow conditions, but charge is quickly generated after blood stasis. It is possible that when red blood cells are stationary, hemoglobin may trap NO that otherwise might neutralize the negatively charged groups.
Animals↗
Psychosocial risk factors during pregnancy. What do family physicians ask about?
OBJECTIVE: To determine whether physician characteristics affect attitudes or practices regarding assessment of psychosocial risk factors during pregnancy, and to evaluate whether an antenatal psychosocial risk factor assessment form would help family physicians. DESIGN AND SETTING: A questionnaire asking physicians to rate the importance of information on a scale of one to five was mailed to all active members of the University of Toronto Department of Family and Community Medicine's Survey Network of Attitudes and Practice (SNAP). PARTICIPANTS: A volunteer sample of physicians doing prenatal and intrapartum obstetrics who are active members of SNAP. The network is made up of full-time faculty in the University of Toronto's family practice units and teaching practice physicians (rural, suburban, and urban) who are interested in participating in research projects. MAIN OUTCOME MEASURES: Response rate was 78%. Responses of the 45 SNAP members who did not practise obstetrics were excluded; 125 of 218 questionnaires mailed were analyzed. RESULTS: Women family physicians rated the form potentially helpful more frequently than their male colleagues. Urban and suburban physicians' concerns differed from those of rural physicians. Alcohol and drug abuse, abuse in the relationship, and acceptance of the pregnancy were rated highly important by physicians. Of the physicians surveyed, 77% thought that an antenatal psychosocial risk assessment form would be of some benefit or very helpful. Only 15% indicated it would be useless or not helpful. CONCLUSION: The importance respondents accorded to risk factors showed little correspondence to the frequency of inquiry about them. The survey confirmed our plan to design an antenatal psychosocial risk factor assessment form.
Adult↗
Potentiation of dark onset feeding in obese mice (genotype ob/ob) following central injection of norepinephrine and clonidine.
Central monoaminergic neurotransmitters have been implicated in the control of food intake in different animal species but it remains unclear whether these same neurochemical systems effectively regulate feeding behaviour in the genetically obese (ob/ob) mouse. Neuropharmacological studies have demonstrated, for example, that microinjection of norepinephrine can elicit a reliable feeding response in the rat, particularly at dark onset. The present study was therefore designed to examine the impact of central injection of norepinephrine (20-160 nmol) and clonidine (5-80 nmol), an alpha 2-adrenoceptor agonist, on food intake in ob/ob mice and lean (+/?) controls. Presatiated obese and lean mice were injected with norepinephrine or clonidine immediately prior to the onset of the dark cycle. Food intake (kcal) was measured 1 h postinjection. Obese mice ingested more food than lean mice under baseline saline conditions. Injection of norepinephrine and clonidine increased eating in both phenotypes, although the ob/ob showed an enhanced feeding response to norepinephrine and clonidine administration. Intracerebroventricular pretreatment with the alpha 2-adrenoceptor antagonist yohimbine (12.5-50 nmol) significantly attenuated the increase in food intake observed in response to central injection of norepinephrine (40 nmol) and clonidine (10 nmol). However, the alpha 1-adrenoceptor antagonist corynanthine (15-60 nmol) or the beta-adrenoceptor antagonist propranolol (25-100 nmol) failed to alter noradrenergic feeding. These results suggest that modification of central alpha 2-noradrenergic function can alter natural feeding in mice, and that the ob/ob is particularly sensitive to this effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Endothelium increases medial hydraulic conductance of aorta, possibly by release of EDRF.
In eight anesthetized New Zealand White rabbits, the aorta was cannulated in situ for measurement of hydraulic conductance (Lp) at different pressures with and without endothelium. De-endothelialization increased Lp at > or = 75 mmHg but not at 50 mmHg. Because endothelium resists transmural water flow, the endothelium must also increase medial Lp at 50 mmHg. To determine whether this effect results from secretion of endothelial-derived relaxing factor (EDRF), Lp was measured in eight rabbits in the presence and absence of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of EDRF synthesis. At 50 mmHg L-NAME reduced Lp from 6.79 +/- 2.19 to 2.59 +/- 1.41 (SD) x 10(-8) (P < 0.05, paired Student's t test). After L-NAME was removed, Lp returned to its control value. At 125 mmHg L-NAME did not significantly change Lp, although endothelial permeability seemed to increase. L-NAME did not affect Lp of nine de-endothelialized vessels at either pressure. An additional five experiments showed that the effect of L-NAME at 50 mmHg was reversed by L-arginine. Eleven additional experiments demonstrated that NG-nitro-D-arginine methyl ester does not affect Lp at 50 mmHg. These results indicate that EDRF increases Lp of the rabbit aorta at low pressures.
Animals↗
Epipodophyllotoxins, alkylating agents, and radiation and risk of secondary leukaemia after childhood cancer.
OBJECTIVE: To investigate the incidence and aetiology of secondary leukaemia after childhood cancer in Britain. DESIGN: Cohort study and a case-control study. SETTING: Britain and population based National Register of Childhood Tumours. SUBJECTS: Cohort of 16,422 one year survivors of childhood cancer diagnosed in Britain between 1962 and 1983, among whom 22 secondary leukaemias were observed. A case-control study of 26 secondary leukaemias observed among survivors of childhood cancer diagnosed in Britain between 1940 and 1983; 96 controls were selected matched for sex, type of first cancer, age at first cancer, and interval to diagnosis of secondary leukaemia. MAIN OUTCOME MEASURES: Dose of radiation averaged over patients' active bone marrow and total accumulated dose of epipodophyllotoxins, alkylating agents, vinca alkaloids, antimetabolites, and antibiotics (mg/m2) given for the original cancer. RESULTS: Cumulative risk of secondary leukaemia within the cohort did not exceed 0.5% over the initial five years beyond one year survival, except that after non-Hodgkin's lymphomas 1.4% of patients developed secondary leukaemia. Corresponding figure for patients treated for non-Hodgkin's lymphomas in the early 1980s was 4%. The relative risk of secondary leukaemia increased significantly with exposure to epipodophyllotoxins and dose of radiation averaged over patients' active bone marrow. Ten patients developed leukaemia after having an epipodophyllotoxin-teniposide in nine cases, etoposide in one. Chromosomal translocations involving 11q23 were observed relating to two secondary leukaemias from a total of six for which there were successful cytogenetic studies after administration of an epipodophyllotoxin. CONCLUSIONS: Epipodophyllotoxins acting alone or together with alkylating agents or radiation seem to be involved in secondary leukaemia after childhood cancer.
Alkylating Agents↗
Yohimbine attenuates clonidine-induced feeding and macronutrient selection in genetically obese (ob/ob) mice.
Biochemical abnormalities in the hypothalamus of the genetically obese (C57B1/6J, ob/ob) mouse, including increased levels of endogenous norepinephrine (NE) in the paraventricular nucleus (PVN) and reduced medial hypothalamic NE metabolism, have been cited as evidence of a CNS defect contributing to altered caloric intake in this genetic strain. In the current study, the alpha 2-antagonist yohimbine (YOH) and the alpha 2-agonist clonidine (CLON) were administered systemically to 6-h meal-feeding obese and lean mice. Yohimbine (3-5 mg/kg, IP) significantly reduced total energy intake and intake of carbohydrate and fat, in both phenotypes, without altering protein intake. In contrast, CLON (25 micrograms/kg, IP) potentiated feeding, resulting in a shift in macronutrient selection toward a significant increase in the proportional intake of carbohydrate. Obese mice, however, showed an enhanced behavioral response to CLON injection. Pretreatment with 1 mg/kg YOH, a dose that alone did not significantly alter energy intake or diet selection, blocked CLON's stimulatory effect on feeding and carbohydrate preference. These results are consistent with a role for alpha 2-noradrenergic receptors in appetite regulation of ob/ob and lean mice and suggest that disturbances in this system may be involved in the development of genetic obesity.
Animals↗
Central injection of 5-hydroxytryptamine reduces food intake in obese and lean mice.
The effects of intracerebroventricular (ICV) administration of 5-hydroxytryptamine creatinine sulphate complex (5-HT), 35-140 nmol, on food intake in genetically obese (ob/ob) and lean mice were investigated. 5-HT (70-140 nmol) decreased feeding in a dose-related manner on 1 h and 2 h postinjection measures. Intake in lean mice was reduced by over 70% of the control condition. Obese mice, however, demonstrated a reduced sensitivity to the anorectic effect of 5-HT, and reduced 1 h intake by only 40% of saline control. Although these results are consisted with a role for serotonin in the control of food intake in mice, the altered sensitivity of the ob/ob to serotonergic stimulation may result, in part, from an impaired satiety control mechanism in this mutant.
Animals↗
Effect of pressure on aortic hydraulic conductance.
This study was performed to determine whether the transmural hydraulic conductance (Lp) of the rabbit aortic wall depends on its distension. In 19 rabbits, the aorta was cannulated in situ and perfused at a given pressure with a physiologically buffered solution containing 4% bovine serum albumin. The output cannula was then occluded to limit fluid flow to that traversing the artery wall. External diameter and transmural fluid flow were measured at three pressures (eight rabbits, group 1) or at four pressures (12 rabbits, group 2) in each vessel. Transmural fluid flow was determined by monitoring the velocity of an air bubble within a buffer-filled tube leading to the input cannula. From group 1 measurements, Lp values (mean +/- SD) at 50, 100, and 150 mm Hg were calculated to be 3.8 +/- 2.8, 3.5 +/- 1.3, and 4.1 +/- 1.2 x 10(-8) cm/sec/mm Hg, respectively. Group 2 measurements gave values of 4.2 +/- 1.6, 3.8 +/- 1.1, 3.8 +/- 1.1, and 4.2 +/- 1.1 x 10(-8) cm/sec/mm Hg at 75, 100, 125, and 150 mm Hg, respectively. Paired Student's t tests indicated no significant change in Lp with pressure. However, linear regression analysis demonstrated a weak correlation between Lp values obtained at 50 and 100 mm Hg (r2 = 0.30) and at 75 and 100 mm Hg (r2 = 0.36). Values of Lp at 100 and 150 mm Hg and at 125 and 150 mm Hg were closely correlated in each case. These results suggest that between 50 and 100 mm Hg the structural properties of the aortic wall change so as to alter Lp but not in the same way in each vessel. Lp may increase or decrease depending on which structural change predominates in a particular vessel.
Animals↗
U.S. health care primary care perspective.
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Humans↗
Thermal preference behavior in preweaning genetically obese (ob/ob) and lean (+/?, +/+) mice.
Impaired nonshivering thermogenesis and lowered rectal temperatures (Tre) are hallmarks that appear early in the postnatal ontogeny of the genetically obese (ob/ob) mouse. Adult obese mice compensate behaviorally for these impairments and do not defend their low Tres. We predicted that, because young mice primarily rely on behavior to ensure thermal homeostasis during preweaning development, the appearance of the obese mouse's thermoregulatory impairment should promote their continued reliance on behavioral thermoregulation compared to lean pups. Accordingly, intact litters of pups from heterozygous lean (C57BL/6J, ob/+) and from homozygous lean (+/+) matings were tested at 6, 12, and 18 days postpartum on a thermal gradient (14-44 degrees C). Obese pups had lower pretest Tres than lean (+/?) littermates at 6 days and lower pretest Tres than both lean littermates and homozygous (+/+) lean control pups at 12 and 18 days. Exposure to the gradient ameliorated these differences (i.e., no posttest Tre differences among phenotypes). Correspondingly, obese pups preferred warmer gradient locations than +/+ pups but similar locations to their phenotypically lean (+/?) littermates until 18 days, when both lean groups preferred similar thermal locations compared to warmer-seeking obese pups. These data support our hypothesis and emphasize the age-dependent impact of the ob gene on altering mouse pups' thermal preferences.
Age Factors↗
Bidirectional effects of clonidine on carbohydrate intake in genetically obese (ob/ob) mice.
Hypothalamic noradrenergic mechanisms contribute to altered caloric intake in genetically obese (C57BL/6J, ob/ob) mice. Noradrenergic mechanisms, principally in the paraventricular hypothalamus and of the alpha 2 subtype, have also been implicated in the macronutrient intake regulation of nonpathological models. Accordingly, this study assessed the extent to which clonidine, an alpha 2 agonist, altered macronutrient intake in genetically obese (ob/ob) and lean (C57BL/6J, +/?) mice. Following adaptation to a 6-h feeding regimen, mice were injected intraperitoneally with either clonidine (0.1, 0.5 mg/kg) or 0.15 M NaCl (Experiment 1) or 0.025 mg/kg clonidine or saline (Experiment 2) 30 min prior to simultaneous access to separate sources of carbohydrate, fat, and protein. Clonidine doses of 0.1 mg/kg or greater reduced total energy intake and intake of carbohydrate and fat (p less than 0.005) in all mice (Experiment 1). However, 0.025 mg/kg clonidine selectively increased ingestion of carbohydrate in obese mice by 212% of vehicle-injected values (p less than 0.001) without altering intake in lean mice (Experiment 2). These results implicate an alpha 2 receptor mechanism in genetic obesity.
Animals↗
Aminoalkyl structural requirements for interaction of lidocaine with the class I antiarrhythmic drug receptor on rat cardiac myocytes.
The structural and physicochemical determinants of binding of lidocaine and several of its aminoalkyl homologs to specific sites associated with the sodium channel were assessed using a radioligand assay and freshly isolated rat cardiac myocytes. The two series of closely related lidocaine homologs that were studied were composed, first, of homologs differing in the length of the link between the arylamide and amine domains of the molecule and, second, of homologs differing in the number of carbons attached to the terminal amine. Drug affinity was measured with a radioligand binding assay, using [3H]batrachotoxinin A 20 alpha-benzoate and freshly isolated cardiac myocytes. The affinities of the homologs were then compared with the pKa values, partition coefficients, distribution coefficients, and molecular structure of the homologs, to determine the relationship between the affinity for the receptor and the physicochemical and structural properties of the drug. Optimal binding was obtained with a link between the arylamide and amine domains that was two carbons in length. The affinity of the drug for the receptor was optimal with four or more amino-terminal carbons, and the precise arrangement of the carbons was not important. Each of the amino-terminal carbons independently contributed 0.3 kcal of free energy of binding, suggesting that the carbons dissolve in a hydrophobic pocket. The evolving picture of a drug structure that is optimal for receptor binding is one of a compound with a two-carbon arylamide-amine link and four or more amino-terminal carbons.
Amides↗
Embryotoxicity of micropore filters used in liquid sterilization.
Microfiltration is the usual method of sterilization of tissue culture media. The filtrates of eight commercial filters were tested for embryotoxicity using mouse embryo growth. Four of five disk filters tested showed embryo-toxicity in the first 5 ml of filtrate and the three larger-capacity filters showed embryotoxicity for up to the first 10 ml of filtrate. The ethylene oxide-sterilized filters appeared to give poorer results than the gamma-irradiated filters. The importance of discarding the initial filtrate or preflushing such filters before use is emphasized.
Animals↗
Excess naevi after chemotherapy in childhood.
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Antineoplastic Agents↗
Milk intakes of genetically obese (ob/ob) and lean mouse pups differ with enhanced milk supply.
Although obese (C57Bl/6J, ob/ob) pups have greater avidity for nonnutritive suckling than leans as early as 15 days postpartum, previous research has not found differences in milk intake between ob/ob and lean mice during the preweaning period. Because ob/ob pups suckle longer than leans, their perseveration should enhance their opportunity to ingest milk if (a) maternal milk supply is not limited and (b) longer sucking durations reflect increased pup willingness to ingest milk. Accordingly, the present study was designed to evaluate the milk intake of ob/ob and lean pups when they had access to an enhanced supply of maternal milk. Intact litters of pups, from heterozygous lean (ob/+) parents, were randomly assigned to be tested at either 6, 12, or 18 days. Pups were neither dam- nor milk-deprived before being cross-fostered successively to milk-replete surrogate dams for 60 min each. Obese pups showed a greater percentage body weight gain (the index of milk intake) than leans did, with younger pups showing larger increments than 18-day-olds. Although early adiposity in ob/ob pups may not rely on increased intake in the single-dam, nest situation, these data emphasize an early predisposition to overeating in this mutant.
Animals↗
Childhood cancers and their association with pregnancy drugs and illnesses.
In a case/control study of 8059 matched pairs, the effect of maternal exposure to drugs and illnesses during pregnancy on the relative risk (RR) of cancer in the child was investigated using conditional logistic regression techniques. Acute respiratory infections, particularly viral infections such as influenza, were associated with a significantly increased RR of all childhood cancers and of neoplasms of the reticulo-endothelial system (RES) in particular, (RR = 1.69 all cancers, RR = 1.81 RES neoplasms, RR = 1.59 solid cancers). An analysis of illnesses according to their physiological effects yielded a significant association between childhood leukaemia and febrile illnesses (RR = 1.27 RES neoplasms). A significant increase in RR was associated with maternal history of epilepsy (RR = 1.31 all cancers) rather than with exposure to anticonvulsant drugs. Vaccines showed a pattern of RR similar to that of acute viral infections. Consumption of antipyretics and analgesics significantly increased the RR of childhood cancer (RR = 1.36 all cancers). An analysis of drugs according to their metabolic reactions yielded a significant association between those undergoing amino acid conjugation (predominantly antipyretics and analgesics) and childhood cancer risk (RR = 1.76 solid cancers).
Female↗
Faecoptysis as the presenting symptom of colonic carcinoma.
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Adenocarcinoma↗