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1.
J Hosp Infect ; 75(1): 47-51, 2010 May.
Article in English | MEDLINE | ID: mdl-20338670

ABSTRACT

Although medical students are known to be at risk for bloodborne infections, there have been no systematic studies, effective intervention programmes, or guidelines for them in China. We developed prevention guidelines, implemented an intervention, and evaluated the effectiveness of knowledge among medical students. This study was designed as a cluster randomised controlled trial. All those who completed a consent form were randomly assigned either to an intervention or to a control group. The intervention group underwent an educational intervention programme consisting of a series of lectures and videos following a baseline survey. The control group completed the same intervention programme after the study was completed. A questionnaire of 25 items was sent to participants three months and nine months after the initial intervention programme. Outcomes measured before and after intervention included knowledge of transmission route, first-aid care, and post-exposure prophylaxis. Pearson's chi(2)-test was used, and the efficacy of students was analysed to control for bias. Intervention in the form of a one-time bloodborne pathogen educational prevention programme for Chinese medical students had little effect on knowledge.


Subject(s)
Blood-Borne Pathogens , Cross Infection/prevention & control , Education/methods , Occupational Diseases/prevention & control , Occupational Exposure/prevention & control , Adult , China , Female , Health Knowledge, Attitudes, Practice , Humans , Male , Students, Medical , Surveys and Questionnaires , Young Adult
2.
Public Health ; 123(7): 484-9, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19560176

ABSTRACT

OBJECTIVE: India tops the list of 22 high-burden tuberculosis (TB) countries. India adopted directly observed treatment - short course (DOTS) under the Revised National Tuberculosis Control Programme (RNTCP) in 1992 and public-private mix DOTS in 2002. This study was conducted to assess the knowledge of doctors in the public and private sectors regarding TB control and management. STUDY DESIGN: Cross-sectional study. METHODS: This study used a self-reported questionnaire based on the RNTCP technical and operational guidelines. One hundred and forty-one doctors were recruited through census sampling; all were registered with the Chest Physicians Association and treating TB using allopathic medicine. The list of doctors was obtained from Lucknow District TB Office, which annually updates and manages the members list of the Chest Physicians Association. This study was conducted in Lucknow, India in February-March 2007. RESULTS: Of 141 doctors, 71% had specialized medical education for treating TB, 60% had received RNTCP training and 69% reported that they follow DOTS methodology for TB treatment. Fifty-six percent of doctors worked in the public sector and 44% worked in the private sector. Forty-nine percent of doctors working in the public sector and 53% working in the private sector correctly reported all TB symptoms as per the RNTCP guidelines. Sixty-six percent of doctors in the public sector and 39% in the private sector reported the correct technique for sputum sampling. Public sector doctors demonstrated better knowledge of drug regimens for sputum smear-positive and sputum smear-negative TB than private sector doctors. Statistical analysis indicated that doctors in the public sector had 2.1 times better knowledge than private sector doctors (odds ratio 2.1; P=0.05). CONCLUSION: Health policy managers and DOTS implementers should encourage all doctors, particularly private sector doctors, to receive RNTCP training and follow DOTS methodology. Improvement is needed in RNTCP training, and emphasis needs to be given to correct diagnosis, management and follow-up of TB patients.


Subject(s)
Health Knowledge, Attitudes, Practice , Physicians , Private Sector , Public Sector , Tuberculosis/drug therapy , Adult , Cross-Sectional Studies , Directly Observed Therapy , Female , Humans , India , Male , Middle Aged , Surveys and Questionnaires
3.
Drug Discov Ther ; 2(1): 2-4, 2008 Feb.
Article in English | MEDLINE | ID: mdl-22504447

ABSTRACT

This article reviewed the process of Traditional Chinese Medicine's modernization on a global scale. This process is motivated by the potential need for traditional medicine as a result of health transitions and increasing drug R&D based on know-how from TCM. The established standards system for modern medicine serves as a basic model yet has limitations in terms of comprehensively evaluating TCM. Spurred by policy committments, research to provide supplements suited to TCM's features and principles is underway. Advanced and interdisciplinary technology and methodology is expected to play an essential role in TCM development.

4.
Body Image ; 4(4): 372-80, 2007 Dec.
Article in English | MEDLINE | ID: mdl-18089283

ABSTRACT

The body composition of 139 Japanese females and 84 Japanese males (aged 18-30 years) was measured using anthropometry to assess gender differences in body perceptions in relation to their measured values. Participants were asked to rate perceptions of their own "heaviness" and "fatness" and these were compared to their BMI and percent body fat (%BF). Japanese females showed a significantly greater desire to lose body weight (-4.20+/-0.6 kg) compared to males (0.27+/-1.4 kg). Females also showed poor understanding of their "heaviness" and "fatness" in relation to actual body composition compared to males. The results confirmed distinct gender differences in body perception in relation to actual body composition and attitudes to weight management. Further promotion of "healthy" body image is recommended for the Japanese population.


Subject(s)
Asian People/psychology , Body Composition , Body Image , Cross-Cultural Comparison , Adipose Tissue , Adolescent , Adult , Anthropometry , Body Mass Index , Female , Humans , Japan , Male , Motivation , Sex Factors , Social Values , Thinness/psychology , Weight Loss
5.
Public Health ; 121(2): 122-9, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17217972

ABSTRACT

BACKGROUND: Long-lasting insecticide-treated nets (LLITNs) are expected to be an important advance in malaria control, but operational experience is still scarce. This study presents some operational findings concerning the introduction of Olyset LLITNs (Sumitomo Chemical Co., Ltd, Japan) in Laos. The study site, Bourapar district, a remote district at high risk of malaria, received Olyset nets during 1999-2000. After distribution of the nets the number of malaria cases in the district hospital decreased for a time, however it began to rise again a year after the intervention. To sustain the effect of the nets, net users were given instructions on maintenance and use. This study aimed to investigate the condition of Olyset nets and the maintenance behaviour of net users after 2-3 years of use, and to examine the associations between maintenance behaviour and the number of malaria episodes during the previous year. METHODS: Questionnaire interviews and inspections of nets were conducted at 240 households during February-March 2003. RESULTS: About 40% of the observed nets had holes/were torn, and the maintenance instructions had not been followed sufficiently. Households following the recommended washing frequency (38.2%) reported fewer malaria episodes during the past year, which demonstrates the importance of the recommended washing frequency in the effective use of the nets. CONCLUSIONS: Our study promotes the idea that, in addition to pursuing high coverage of LLITNs, more effort should be made to ensure that nets are kept in good condition in future LLITN programmes.


Subject(s)
Bedding and Linens/supply & distribution , Health Behavior , Health Knowledge, Attitudes, Practice , Insecticides , Maintenance/standards , Malaria/prevention & control , Mosquito Control/instrumentation , Adult , Bedding and Linens/standards , Cross-Sectional Studies , Episode of Care , Family Characteristics , Health Education , Humans , Hygiene , Insecticides/administration & dosage , Maintenance/methods , Malaria/epidemiology , Middle Aged , Mosquito Control/methods , Mosquito Control/standards , Socioeconomic Factors , Surveys and Questionnaires , Thailand/epidemiology
6.
Drug Discov Ther ; 1(1): 12-3, 2007 Aug.
Article in English | MEDLINE | ID: mdl-22504359

ABSTRACT

China's Good Manufacturing Practice (GMP) standards that mainly parallel WHO standards were made compulsory in 2004. However, GMP implementation had both positive as well as negative impacts on the pharmaceutical industry, with negatives including pharmaceutical companies suffering economic hardships, poor execution of GMP standards, and sequent health scares. This report briefly describes the problems with GMP implementation in China.

7.
Public Health ; 120(5): 400-11, 2006 May.
Article in English | MEDLINE | ID: mdl-16504227

ABSTRACT

OBJECTIVES: Nicaragua is one of two low-income countries in the Latin Americas. The objectives of this study were to clarify the nutritional status of children aged 0-23 months and to identify the associated factors in rural Nicaragua. STUDY DESIGN AND METHODS: This was a cross-sectional study; a questionnaire survey was performed and anthropometric measurements were taken in Granada province, Nicaragua. RESULTS: Seven hundred and fifty-six mothers with at least one child aged 0-23 months took part in this study. The proportion of underweight children [weight-for-age Z-score <-2 standard deviations (SD)] was 10.3%, while 30.1% of children exhibited stunted growth (height-for-age Z-score <-2 SD) and 5.0% were wasted (weight-for-height Z-score <-2 SD). Mothers' illiteracy or lack of formal education [odds ratio (OR)=3.476, P<0.01], a history of respiratory infection (OR=1.821, P<0.05) and a birth weight below the median (<3000 g; OR=1.704, P<0.05) were identified as risk factors for stunted growth. Breastfeeding for more than 12 months (OR=2.031, P<0.01), absence of participation in child growth monitoring (OR=1.956, P<0.05) and female gender of the child (OR=1.884, P<0.05) were identified as risk factors for underweight. DISCUSSION: Despite the steady economic development in Nicaragua since 1990, child nutritional status has not improved as much as might be expected. The present study revealed that a mother's favourable sociodemographic characteristics and her active participation in health activities, such as child growth monitoring, can protect against child malnutrition, particularly against underweight. More attractive health education or antenatal care programmes might lead to substantial improvements in maternal and child health in this small, poor community.


Subject(s)
Infant Nutritional Physiological Phenomena , Nutritional Status , Thinness/epidemiology , Adult , Breast Feeding/epidemiology , Cross-Sectional Studies , Educational Status , Female , Growth , Humans , Infant , Infant Care/statistics & numerical data , Infant, Newborn , Male , Maternal Age , Middle Aged , Nicaragua/epidemiology , Poverty , Risk Factors , Sex Factors
8.
Epidemiol Infect ; 133(6): 1131-42, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16274512

ABSTRACT

Studies of non-polio enterovirus prevalence and transmissibility in developing countries are limited and few studies have investigated specific risk factors for infection. An epidemiological survey of non-polio enterovirus among families in Mongolia was conducted in the late summer of 2003. Stools of 122 healthy persons were collected weekly for 5 weeks. Eight serotypes of non-polio enteroviruses (echovirus 30, 33, 12, 25, coxsackievirus A10, A2, A4, A24) were isolated from 62 persons, with an overall isolation rate of 51%, and 64% and 35% among children under 10 years and adults over age 21 years. Fifty-four per cent of isolations were due to intrafamilial infection. Analysis of risk factors for infection suggested contamination of indoor kitchen, bathroom, toilet, and waste disposal area. Hand washing after defecation was protective against infection. Our study findings stress the importance of hand washing and cleaning hygienic facilities to prevent infection by enteric viruses in the home environment.


Subject(s)
Echovirus Infections/epidemiology , Enterovirus Infections/epidemiology , Enterovirus/isolation & purification , Adult , Child , Child, Preschool , Enterovirus/immunology , Enterovirus Infections/transmission , Female , Housing/standards , Humans , Infant , Male , Middle Aged , Mongolia/epidemiology , Prevalence , Risk Factors , Seroepidemiologic Studies
9.
Int J Gynaecol Obstet ; 91(1): 105-12, 2005 Oct.
Article in English | MEDLINE | ID: mdl-16098977

ABSTRACT

OBJECTIVE: To ascertain and compare compliance with UN emergency obstetric care (EmOC) recommendations by public health care centers in Pakistan's Punjab and Northwest Frontier Province (NWFP) provinces. METHOD: Cross-sectional data were collected from July through September 2003 using UN process indicators. From each province, 30% of districts (n=19); were randomly selected; all public health facilities providing EmOC services (n=170) were included. RESULTS: The study found that out of 170 facilities only 22 were providing basic and 37 comprehensive EmOC services in the areas studied. Only 5.7% of births occurred in EmOC health facilities. Met need was 9% and 0.5% of women gave birth by cesarean section. The case fatality rate was a low 0.7%, probably due to poor record keeping. Access and several indicators were better in NWFP than in Punjab. CONCLUSION: Almost all indicators were below UN recommendations. Health policy makers and planners must take immediate, appropriate measures at district and hospital levels to reduce maternal mortality.


Subject(s)
Emergency Medical Services , Maternal Health Services/standards , Obstetrics/standards , Cross-Sectional Studies , Delivery, Obstetric , Female , Health Services Accessibility , Health Services Needs and Demand , Humans , Maternal Health Services/statistics & numerical data , Maternal Mortality , Maternal Welfare , Pakistan/epidemiology , Pregnancy , Prenatal Care , Public Health Administration/standards , United Nations
10.
Eur J Clin Nutr ; 59(7): 887-90, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15915154

ABSTRACT

A cross-sectional study was undertaken to assess the nutritional status of children aged 3-15 y in remote villages of Lao PDR. Study sites were chosen from two provinces: Luang namtha (north) and Sekong province (south). All the sampled 1075 children were measured for anthropometry, following the standard methods. Dietary intake, morbidity and socio-economic data were obtained by interviews with parents. This study confirmed the high prevalence of growth retardation among children, as well as persistent food insecurity in the remote areas of Lao PDR. Prevalence of stunting was 74.1% in Luang namtha and 62.6% in Sekong province, with school-aged children being worse-off than under-five ones. Children's diets were inadequate in quality as well as in quantity, with very limited availability of rice and other food items throughout the year. Our findings also suggest the negative outcomes of government's development programme were often overlooked, and that more attention should be paid on the fragile living conditions in the resettlement villages, especially for the ethnic minority.


Subject(s)
Child Nutrition Disorders/epidemiology , Diet , Nutritional Status , Rural Health , Adolescent , Anthropometry , Child , Child, Preschool , Cross-Sectional Studies , Feeding Behavior , Female , Food Supply , Humans , Laos/epidemiology , Male , Nutrition Surveys , Rural Population/statistics & numerical data
11.
J Epidemiol ; 11(6): 255-62, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11769943

ABSTRACT

Following the Pan American Health Organization (PAHO) recommendation on measles elimination, the Western Pacific Region of WHO (WPR) is emphasizing accelerated measles control programme especially since the achievement of polio eradication in WPR in 2000. This includes upgraded surveillance and mass measles vaccination campaign for children aged 9 months to 4 years. However, there are limited scientific evidences supporting the feasibility of this programme in Laos. To examine measles elimination feasibility in the country, we conducted measles outbreak investigation using immunoglobulin M (IgM). From March 1999 to March 2000, we conducted 7 outbreak investigations. At the outbreak sites, we examined clinical manifestations of cases and collected individual data. About five blood samples were drawn from each outbreak, and IgM antibodies to measles were tested. Of 7 investigated outbreaks, 5 were confirmed as measles, one was chickenpox, and one occurred in the inaccessible area due to flooding. In a village of high land Lao, blood drawn was refused. Of 185 cases, 64 (34.6%) cases were immunized, and 110 (59.5%) were unimunized. The estimated vaccine efficacy is 67.9%. The number of measles cases among school-aged children was 74 (40.0%), which represented 2.5% of the total population in investigated villages. Our findings showed various difficulties of the surveillance and the limited outcomes of mass measles vaccination campaign under the accelerated measles control programme by WPR. Efforts to improve cold chain as well as increasing routine immunization coverage must be the priority of measles control.


Subject(s)
Immunoglobulin M/blood , Measles/diagnosis , Measles/epidemiology , Antibodies, Viral/blood , Diagnosis, Differential , Disease Outbreaks , Feasibility Studies , Female , Humans , Infant , Laos/epidemiology , Male , Measles/immunology , Measles Vaccine/immunology , Population Surveillance
12.
Lancet ; 356(9240): 1487-8, 2000 Oct 28.
Article in English | MEDLINE | ID: mdl-11081534

ABSTRACT

The declaration of poliomyelitis eradication in the western pacific region is scheduled for Oct 29, 2000, in Kyoto, Japan. Our survey in the border areas of the southeast Asia region, however, revealed that there remains a risk of re-emergence and importation of poliomyelitis into Laos. We report the evidence based on our border area investigations during the past 4 years under the bilateral supervision of the governments of Laos and Japan.


Subject(s)
Poliomyelitis/prevention & control , Child, Preschool , Humans , Infant , Infant, Newborn , Laos/epidemiology , Muscle Hypotonia/prevention & control , Paralysis/prevention & control , Poliomyelitis/epidemiology , Poliovirus Vaccine, Oral , Population Surveillance , Risk Factors
13.
J Trop Pediatr ; 45(3): 185-90, 1999 06.
Article in English | MEDLINE | ID: mdl-10401206

ABSTRACT

The underdeveloped health infrastructure and limited epidemiological data on polio are major obstacles to the establishment of the acute flaccid paralysis (AFP) surveillance system in Lao People's Democratic Republic (Lao PDR). We initiated a nationwide active case search for case investigations at the community level in March 1994 to support the development of the AFP surveillance system. We identified 164 polio cases that occurred between 1979 and 1993 in 511 villages, indicating that wild poliovirus had circulated extensively during that period. Of these, only 59 (36 per cent) had visited health facilities, and polio was diagnosed in 15 (9 per cent). As national immunization days (NIDs) progressed, the number of polio cases decreased to an undetectable level after 1994. The active case search was useful for educating the local staff about AFP and the components of a surveillance system, and as an adjunct to national AFP surveillance programme in the country as it approaches the goal of polio eradication.


Subject(s)
Poliomyelitis/epidemiology , Population Surveillance/methods , Age Distribution , Child, Preschool , Health Services/statistics & numerical data , Humans , Infant , Laos/epidemiology , Poliomyelitis/diagnosis , Poliomyelitis/prevention & control , Poliomyelitis/virology , Vaccination/methods
14.
Eur Respir J ; 9(4): 741-6, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8726939

ABSTRACT

To elucidate the role of tachykinins in bronchoconstriction induced by intravenous administration of bradykinin (Bk), we studied the effects of FK224, a neurokinin-1 (NK1) and neurokinin-2 (NK2) receptor antagonist, on the bronchoconstriction induced by intravenous (i.v.) administration of Bk (5-100 micrograms.kg-1) in guinea-pigs. Total pulmonary resistance -(RL) was measured using a pressure-volume sensitive body plethysmograph in anaesthetized artificially ventilated guinea-pigs pretreated with atropine (1 mg.kg-1) and propranolol (1 mg.kg-1). In the control group, i.v. administration of Bk produced a dose-dependent increase in RL. In animals pretreated with FK224, bronchoconstriction induced by higher doses of Bk (10, 50 and 100 micrograms.kg-1) was significantly reduced, whilst the bronchoconstriction caused by lower doses of Bk (5 and 7.5 micrograms.kg-1) was not. Pretreatment with a combination of FK224 and indomethacin markedly inhibited the bronchoconstriction induced by each dose of Bk compared with the groups pretreated with FK224 alone. Although pretreatment with indomethacin alone significantly reduced RL at a high dose of Bk (50 micrograms.kg-1), the reduction was significantly lower than that produced by a combination of FK224 and indomethacin. These results suggest that intravenous administration of a high dose of bradykinin causes bronchoconstriction both by cyclo-oxygenase products and by release of tachykinins.


Subject(s)
Bradykinin/adverse effects , Bronchoconstriction/drug effects , Neurokinin-1 Receptor Antagonists , Peptides, Cyclic/pharmacology , Receptors, Neurokinin-2/antagonists & inhibitors , Tachykinins/physiology , Animals , Dose-Response Relationship, Drug , Drug Therapy, Combination , Guinea Pigs , Indomethacin/pharmacology , Male , Plethysmography, Whole Body , Tachykinins/metabolism
15.
Biopharm Drug Dispos ; 16(2): 91-103, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7780050

ABSTRACT

We synthesized 14C-warfarin hexadecyl ether (14C-WHE) by addition of a palmityl moiety to the hydroxyl group at the 4-position of 14C-warfarin, a compound known to bind to serum albumin. 14C-WHE preferentially bound to the lipoproteins, low-density lipoprotein (LDL) and high-density lipoprotein (HDL), in mouse plasma both in vitro and in vivo. 14C-Warfarin mainly concentrated in the liver immediately after intravenous administration to mice bearing M5076 sarcoma, and was found at only low concentrations in other tissues including the tumour. 14C-WHE highly distributed to the tumour, adrenal, and spleen, as well as the liver. These tissues coincided with those in which human 125I-LDL was vigorously incorporated. The results indicate that chemical modification of an agent, giving it high lipophilicity, will enable it to bind to lipoproteins after intravenous administration. These modifications raise the possibility of lipoproteins as endogenous targeting carriers into tumour cells, which have high LDL-receptor activity.


Subject(s)
Lipoproteins/blood , Palmitates/administration & dosage , Palmitates/pharmacokinetics , Sarcoma, Experimental/drug therapy , Warfarin/analogs & derivatives , Albumins/metabolism , Animals , Carrier Proteins/blood , Drug Carriers , Female , Lipoproteins, HDL/blood , Lipoproteins, HDL/metabolism , Lipoproteins, LDL/blood , Lipoproteins, LDL/metabolism , Liver/metabolism , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Molecular Probes , Palmitates/blood , Protein Binding , Sarcoma, Experimental/blood , Sarcoma, Experimental/metabolism , Serum Albumin/metabolism , Tissue Distribution , Warfarin/administration & dosage , Warfarin/blood , Warfarin/pharmacokinetics
16.
Pharm Res ; 12(3): 370-5, 1995 Mar.
Article in English | MEDLINE | ID: mdl-7617523

ABSTRACT

RS-1541 is a 13-O-palmitoyl derivative of rhizoxin, an inhibitor of tubulin polymerization. After intravenous administration of RS-1541 to mice bearing M5076 sarcoma, the maximal inhibitory effect of RS-1541 on DNA synthesis in the tumor was observed 24 h after administration, in agreement with the Cmax of rhizoxin produced from RS-1541, but not with the Cmax of RS-1541. The inhibitory effect after RS-1541 was much higher than that after rhizoxin itself. In the spleen, thymus and bone marrow, DNA synthesis was strongly inhibited by rhizoxin but not by RS-1541. After administration of RS-1541, no significant amounts of rhizoxin were detected in the tissues, except for the tumor. In acute toxicity tests, RS-1541 appeared to be less toxic than rhizoxin. These results indicate that RS-1541 possesses a high tumor-selective effect compared with rhizoxin, because of the selective production of rhizoxin in the tumor after administration of RS-1541.


Subject(s)
Antibiotics, Antineoplastic/pharmacology , DNA, Neoplasm/biosynthesis , Thymidine/metabolism , Animals , Antibiotics, Antineoplastic/toxicity , Dose-Response Relationship, Drug , Female , Injections, Intravenous , Lactones/pharmacology , Lactones/toxicity , Macrolides , Male , Mice , Sarcoma, Experimental/metabolism , Time Factors
17.
Biopharm Drug Dispos ; 15(2): 93-107, 1994 Mar.
Article in English | MEDLINE | ID: mdl-8011970

ABSTRACT

The tumour uptake as well as the anti-tumour activity of RS-1541 (palmitoyl rhizoxin), a potent antineoplastic agent, were investigated in mice bearing M5076 sarcoma. After intravenous administration, 14C-RS-1541 preferentially bound to the lipoproteins, to which 14C-rhizoxin did not bind. 14C-RS-1541 showed persisting high concentrations of radioactivity in the plasma (T 1/2 alpha, 4.9 h). The uptake of radioactivity by the tumour was second to those by the liver and spleen, and several times greater than those by the other tissues. Selective and sustained uptake by the tumour was also demonstrated by whole-body autoradiography. A considerable amount of rhizoxin was detected only in the tumour after administration of 14C-RS-1541, and the area under the tissue-concentration-time curve (AUCt) and the mean residence time (MRT) of rhizoxin in the tumour were much higher than those after administration of 14C-rhizoxin itself. The rhizoxin formation in the tumour was significantly reduced by chloroquine, a lysosomal enzyme inhibitor. RS-1541 showed a higher therapeutic activity than rhizoxin. At a 4 mg kg-1 dose, the maximum growth inhibition was 92% for RS-1541 and 41% for rhizoxin. These results indicate that RS-1541, but not rhizoxin, is taken up by the tumour via endocytosis, most likely via the low-density-lipoprotein receptor, after binding to lipoproteins. Thus, RS-1541 was considered to exhibit sustained high concentration in tumours and potent anti-tumour activity.


Subject(s)
Antineoplastic Agents/pharmacokinetics , Lipoproteins, LDL/blood , Animals , Antineoplastic Agents/metabolism , Antineoplastic Agents/pharmacology , Autoradiography , Carbon Radioisotopes , Chloroquine/pharmacology , Female , In Vitro Techniques , Lactones/analysis , Lactones/metabolism , Lactones/pharmacokinetics , Lactones/pharmacology , Macrolides , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Neoplasm Transplantation , Protein Binding , Sarcoma, Experimental/drug therapy , Sarcoma, Experimental/metabolism , Skin Neoplasms/drug therapy , Skin Neoplasms/metabolism , Tissue Distribution
18.
J Nutr ; 123(10): 1693-702, 1993 Oct.
Article in English | MEDLINE | ID: mdl-8410360

ABSTRACT

To examine the effect of different saturated fatty acids on the dietary cholesterol-induced elevation of serum cholesterol concentration and suppression of LDL catabolism, for 4 wk hamsters were fed purified diets containing 8% purified fats in which saturated fatty acids, lauric, myristic, palmitic and stearic acids were the sole variable. The dietary fat was composed of 50% saturated fatty acid, 30% oleic acid and 20% linoleic acid (polyunsaturated:saturated = 0.4). In hamsters fed the cholesterol-containing diet, fat containing stearic acid, compared with the fats containing other saturated fatty acids resulted in greater fractional catabolic rate of [125I]-labeled homologous LDL, greater fecal excretion of neutral steroids and lower liver cholesterol concentration, although the elevation of serum cholesterol concentration due to consuming a cholesterol-containing diet was not ameliorated. Stearic acid fat resulted in greater excretion of fecal fatty acids and lower apparent absorption of the dietary fats in hamsters fed diets with and without cholesterol. In hamsters fed the cholesterol-free diets, type of dietary fat did not affect the fractional catabolic rate of LDL, although stearic acid fat resulted in greater fecal neutral steroid excretion and lower serum and liver cholesterol concentrations. These observations suggested that purified fat containing stearic acid results in lower plasma cholesterol concentration in hamsters via stimulation of neutral steroid excretion, but addition of cholesterol to the diets obscures this effect.


Subject(s)
Cholesterol, Dietary/administration & dosage , Cholesterol/blood , Dietary Fats/pharmacology , Feces/chemistry , Lipoproteins, LDL/metabolism , Stearic Acids/pharmacology , Steroids/metabolism , Adipose Tissue/metabolism , Animals , Cricetinae , Dietary Fats/administration & dosage , Fatty Acids/metabolism , Lipid Metabolism , Lipids/blood , Liver/metabolism , Male , Mesocricetus , Stearic Acids/administration & dosage , Triglycerides/metabolism
19.
Eur J Drug Metab Pharmacokinet ; 17(2): 103-13, 1992.
Article in English | MEDLINE | ID: mdl-1425808

ABSTRACT

Pravastatin sodium (pravastatin) is a potent inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and was found to be highly effective in animals and humans, in lowering the plasma cholesterol level by inhibiting cholesterol synthesis selectively in the liver. In the present study the disposition and metabolism of pravastatin was studied in rats, dogs and monkeys using [14C]-labelled compound. The extent of absorption was approximately 70% in rats and 50% in dogs. Tissue distribution examined by both whole-body autoradiography and radioactivity measurement demonstrated that the drug was selectively taken up by the liver, a target organ of the drug, and excreted via bile mainly in unchanged form. Since pravastatin excreted by the bile was reabsorbed, the enterohepatic circulation maintained the presence of unchanged pravastatin in the target organ. The profiles of metabolites were studied in various tissues and excreta and a metabolic pathway of pravastatin was proposed.


Subject(s)
Pravastatin/pharmacokinetics , Animals , Bile/metabolism , Dogs , Enterohepatic Circulation , Intestinal Absorption , Liver/metabolism , Macaca fascicularis , Male , Rats , Rats, Wistar , Tissue Distribution
20.
Biochem Pharmacol ; 43(4): 667-70, 1992 Feb 18.
Article in English | MEDLINE | ID: mdl-1540221

ABSTRACT

The transport mechanism of pravastatin, a new cholesterol-lowering drug, was compared in vitro with rat hepatocyte primary culture and mouse skin fibroblasts (L-cells). The uptake of 14C-labeled pravastatin by cultured hepatocytes was temperature- and dose-dependent. The temperature-dependent uptake as a function of [14C]pravastatin concentration showed saturation kinetics with Km = 32.2 microM and a maximal uptake rate of 68 pmol/mg protein/min. The uptake of pravastatin was inhibited significantly by metabolic inhibitors such as rotenone, oligomycin A, antimycin A, 2,4-dinitrophenol and KCN. Unlabeled pravastatin as well as R-416 and R-195, structural analogues of pravastatin, effectively competed for the hepatic uptake of [14C]pravastatin at 37 degrees. These results indicate that pravastatin is taken up by the liver by an active transport. In contrast, the transport of pravastatin by L-cells was temperature-independent and non-saturable, suggesting that the uptake of pravastatin by L-cells is mediated by passive diffusion. The marked difference in the uptake mechanism of pravastatin between hepatocytes and L-cells may account for a unique feature of this drug in that the uptake and inhibition of cholesterol biosynthesis occur selectively in the liver.


Subject(s)
Liver/metabolism , Pravastatin/metabolism , Animals , Biological Transport, Active , Cells, Cultured/drug effects , Cells, Cultured/metabolism , Kinetics , L Cells/drug effects , L Cells/metabolism , Liver/drug effects , Male , Mice , Pravastatin/antagonists & inhibitors , Pravastatin/pharmacology , Rats , Rats, Inbred Strains , Temperature
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