ABSTRACT
BACKGROUND: The WHO's Health Promoting Schools (HPS) framework is based on an understanding of the reciprocal relationship between health and education, and the need to take a holistic approach to health promotion in schools. We aim to clarify the degree to which the HPS framework is reflected in the national policies of eight target countries and the issues surrounding its successful implementation. METHODS: Date were collected through two expert workshops with participants from eight Asian countries: Cambodia, China, Japan, Korea, Lao PDR, Nepal, the Philippines, and Thailand. In the first workshop, data collected on national policy were mapped against the HPS framework. From this, key issues were identified, and follow-up data collection was conducted in each country for a second workshop. RESULTS: We identified a policy shift toward the HPS framework in six out of the eight countries. Neither Japan nor Korea had changed their national policy frameworks to reflect an HPS approach; however, in the latter, model programs had been introduced at a local level. We identified various barriers to successful implementation, especially in relation to mental health and wellbeing. CONCLUSION: Given the recent shift toward the HPS approach in six out of the eight countries in this study, there is a need to conduct research to assess the impact of this framework on the health and wellbeing of students and school staff. At the same time, we call for more dialog in the context of Japan to explore the possible benefits of introducing the HPS framework into schools.
Subject(s)
Health Promotion , School Health Services , Humans , Policy , Schools , ThailandABSTRACT
OBJECTIVE: Prostate cancer is a common malignancy and patients may progress to castration-resistant prostate cancer (CRPC). Among patients with CRPC, fatigue is a common symptom associated with current treatments. The aim of this real-world study was to describe patient-reported fatigue in Japanese patients treated with androgen receptor-axis-targeted therapies for CRPC. METHODS: Data of this observational study were collected in a quantitative phase for the description of patient-reported fatigue, and a qualitative phase for elicitation of fatigue perception and barriers to reporting fatigue. RESULTS: In the quantitative phase (N = 22), fatigue was investigated in two formats: symptoms report and Brief Fatigue Inventory (BFI). In the report of the symptoms, 12 patients reported tiredness, and four moderate-to-severe tiredness during treatment. In the BFI, all patients reported fatigue; eight reported moderate-to-severe fatigue. The most affected BFI domain was mood: five patients reporting moderate-to-severe impact. In interviews (qualitative phase; N = 8), diverse patient experience on fatigue was observed, including apathetic feelings, affected speed and distance during the walk, negative impact on profession, housework, or driving, reduced outgoing activity, and difficulty in enjoying time with grandchildren or travel. Five out of eight patients communicated fatigue to their physicians but received diverse reactions. CONCLUSION: Patient interviews highlighted the impact of fatigue on patients' lives and difficulties in communicating fatigue to physicians. Fatigue frequency after medication may need to be monitored and its burden is considered to provide treatment that meets the needs, wishes, and circumstances of each patient. Further research is needed to elucidate how fatigue affects patients' lives, and underscore patient-physician communication difficulties.
Subject(s)
Physicians , Prostatic Neoplasms, Castration-Resistant , Communication , Fatigue/epidemiology , Fatigue/etiology , Humans , Japan , Male , Prostatic Neoplasms, Castration-Resistant/complications , Prostatic Neoplasms, Castration-Resistant/drug therapyABSTRACT
BACKGROUND: Undernutrition and overnutrition have been considered separate challenges caused by the distinct factors in distinct settings. The double burden of malnutrition is defined as the coexistence of both undernutrition and overnutrition, which has now spread globally, especially in low- and middle-income countries. In Kenya, the double burden of malnutrition is present in the capital city but the situation in rural areas currently remains unknown. The aim of this study was therefore to analyze nutritional status in rural Kenya. METHODS: Data from height and weight measurements conducted by teachers in the third term of school year 2013 were collected from primary schools. Teachers were trained by experts before starting the measurements. The Z-scores of height-for-age, weight-for-age, and body mass index-for-age were calculated using AnthroPlus, and nutritional status was defined according to the World Health Organization guidelines. RESULTS: Data analyzed from 7,447 pupils (3,763 boys and 3,684 girls) showed that 12.4% were stunted and 7.8% were underweight among those ≤120 months old, and 11.7% were thin among those >120 months old. Boys were more likely to be stunted than girls. Boys were more likely to be underweight and girls were more likely to be overweight in the older age group. CONCLUSION: The double burden of malnutrition was not found, and undernutrition was still common among schoolchildren in the study area. However, it is important to monitor nutritional status due to adverse effects of rapid urbanization. Height and weight measurements in schools may be useful for monitoring the nutritional status of schoolchildren.
Subject(s)
Malnutrition , Aged , Child , Female , Humans , Kenya/epidemiology , Male , Malnutrition/diagnosis , Malnutrition/epidemiology , Nutritional Status , Prevalence , Thinness/epidemiologyABSTRACT
BACKGROUND: There are not clear evidence to date evaluating patients' and caregivers' preferences for the recombinant-human growth hormone (r-hGH) injection in children in Japan. This study aimed to quantitatively evaluated the factors driving preferences for daily r-hGH injections among Japanese children with growth hormone deficiency (GHD) or their caregivers and to determine the relative importance of treatment delivery factors. METHODS: This study was performed among Japanese children with GHD or their caregivers who visited a specialized clinic in Japan as part of their routine care. The participants were asked to complete a web-based discrete choice experiment (DCE) questionnaire. RESULTS: Choice-based conjoint analysis was used to evaluate the relative importance of the attributes of the choice predictors and determine utility scores for each attribute. Of the 47 respondents who participated in this study, 41 were caregivers who responded on behalf of the patients, the remaining six were patients who completed the DCE themselves. The injection schedule was found to be the most important factor for both patients and caregivers; a once-weekly injection schedule was preferred over a daily injection schedule. Storage and preparation was deemed more important to patients than it was to caregivers, with patients preferring storage at room temperature even if it required additional mixing (reconstitution). Both patients and caregivers showed a clear preference for devices that offered a dose-setting memory. CONCLUSIONS: A less frequent injection schedule may enhance adherence to r-hGH treatment and expected improve quality of life for GHD patients over the long term.
Subject(s)
Dwarfism, Pituitary , Human Growth Hormone , Child , Choice Behavior , Human Growth Hormone/therapeutic use , Humans , Japan , Patient Preference , Quality of LifeABSTRACT
BACKGROUND: Japanese schools hold annual sports events in which all pupils participate. These events include activities such as walking, running, and swimming competitions. METHODS: We analyzed literature on school sports events in Japan. RESULTS: In addition to the physical education classes, which are part of the curriculum, Japanese schools hold annual sports events in which all pupils participate. These school events include activities such as walking, running, swimming, and ball game competitions, skiing, and climbing. School sports events offer participants an opportunity for holistic education as well as cultivating a variety of virtues such as cooperation, a sense of solidarity, teamwork, and responsibility. A popular sports event held countrywide is undokai. Undokai has a style that is unique to Japan. They usually take one day and include individual and group competitions. The pupils participate in a variety of activities including a foot race, relay race, group gymnastics, and group activities. The undokai is an important event in both the school and its surrounding community. The potential benefit of undokai is often considered in terms of social capital. However, the competitive nature of undokai may generate negative feelings in the children who participate. CONCLUSIONS: Further research on the potential of sports events such as undokai is necessary.
Subject(s)
Schools , Sports , Adolescent , Child , Humans , Japan , Physical Education and Training , Running , Skiing , Swimming , WalkingABSTRACT
The Kenyan government established the Kenyan Comprehensive School Health Program (KCSHP) on the basis of Kenyan National School Health Policy. A KCSHP pilot project was carried out in eight primary schools in Mbita Sub-County of Homa Bay County in the Nyanza Region from 2012 to 2017. This pilot project provided health facilities and support for evaluation with a school health checklist, and organized teacher training on health education, a child health club, and school-based health check-ups. The present study aimed to examine the appropriateness and reliability of the strategy of the second KCSHP pilot project in Kenya. We analyzed data from self-administered questionnaires targeted at pupils in seventh-grade in the eight primary schools. The questionnaire consisted of questions on health-related knowledge, attitudes and practices, self-evaluated physical and mental health status, self-awareness of health control, subjective happiness, recognition on the importance of learning about health in school, absenteeism, and sense of school belongingness. The project contributed to improving health-related knowledge, attitudes and practices, self-evaluated health status, sense of school belongingness, recognition on the importance of learning about health in school, self-awareness of health control, and absenteeism. On the contrary, subjective happiness did not improve significantly.
Subject(s)
Health Promotion , Schools , Child , Health Knowledge, Attitudes, Practice , Humans , Kenya , Pilot Projects , Reproducibility of Results , School Health ServicesABSTRACT
There is growing evidence supporting the effectiveness of a comprehensive school health program. However, implementation in developing countries is a challenge. Furthermore, the available information on the association between a comprehensive school health program and students' academic attainment is limited. In Kenya, a project to verify the effects of a comprehensive school health program was carried out in Mbita sub-county, Homa Bay County from September 2012 to August 2017. This study aimed to clarify the improvement of school health during the project years and the association between school health and students' academic attainment. Primary schools in Mbita sub-county were selected as study sites. We assessed 44 schools' scores on a school health checklist developed from the Kenyan Comprehensive School Health Program, the students' mean score on the Kenya Certificate of Primary Education (KCPE), and absenteeism during the project years (2013-16). The mean school health checklist score (n = 44 schools) was 135.6 in 2013, 169.9 in 2014, 158.2 in 2015 and 181.3 in 2016. The difference of the mean score between 2013 and 2016 was significant. In addition, correlation analysis showed a significant association between mean KCPE score in the project years and school health checklist score (Pearson's coefficient was 0.43, p = 0.004). The results of this study suggest improvements of school health by the implementation of the Kenyan Comprehensive School Health Program and students' academic attainment.
Subject(s)
Schools , Students , Educational Status , Health Promotion , Humans , KenyaABSTRACT
BACKGROUND: Despite recognition of the risks of alcohol use and importance of prevention from an early age, the effectiveness of school-based interventions in Africa has not been clarified. OBJECTIVE: We aimed to identify effective school-based alcohol use prevention interventions in Africa. METHODS: We searched eight databases for peer-reviewed articles published until February 3, 2019 that reported on randomized controlled trials, cluster randomized controlled trials, controlled clinical trials, pre-post quasi-experimental studies, cohort studies, and case-control studies. The full-texts of relevant studies were searched. RESULTS: Four of 2797 papers met our eligibility criteria. All reported interventions targeted secondary school students in South Africa and were incorporated in the school curriculum. The interventions comprised multi-component activities with participatory and peer educational methods, and applied modified programs originally developed in the US. However, intervention effects were inconsistent among studies, although the interventions tended to have a positive effect on non-drinkers at baseline, with stronger effects in girls. CONCLUSION: interventions had positive effects on students that were non-drinkers at baseline, especially girls. Although we could not find robust evidence that school-based interventions changed attitudes, frequency/quantity of drinking, and intentions to use alcohol, one intervention showed an increase in students' alcohol refusal self-efficacy.
Subject(s)
Adolescent Behavior , Alcohol Drinking/prevention & control , School Health Services/statistics & numerical data , Students/psychology , Adolescent , Alcohol Drinking/epidemiology , Female , Humans , Male , Peer Group , SchoolsABSTRACT
OBJECTIVE: Sports activities is broadly utilized to support well-being of youth after a disaster or conflict. However, scientific validation of programs have not been conducted. The Mastery Approach to Coaching (MAC) is a coaching-education program on sports activities. The MAC reported to have a positive effect on youngsters' self-esteem. As self-esteem is generally known to be beneficial for mental status, we tested the effect of a MAC program on students' self-esteem in a disaster-affected area: Leyte, Philippines. We recruited 10th grade students from three schools; one school was allocated to the MAC intervention and the two schools to the control group. All schools were encouraged to involve students in volleyball from January to February 2015. In January 2015, MAC workshop was conducted in the intervention school before the sports activity. RESULTS: A total of 293 students completed the questionnaires. The intervention school (n = 51) showed a significant change in self-esteem, with the mean score increasing from 20.2 to 21.1 (p = 0.02). Neither school in the control group showed the significant change. The result showed the feasibility and a positive effect of sports activity with the MAC. However, further investigation should be conducted. Trial registration UMIN Clinical Trials Registry ID: UMIN000033197 on June 30th 2018. Retrospectively registered.
Subject(s)
Adolescent Behavior/psychology , Disasters , Exercise Therapy/methods , Mentoring/methods , Schools , Self Concept , Social Support , Sports/psychology , Students/psychology , Adolescent , Cyclonic Storms , Female , Humans , Male , Philippines , Treatment OutcomeABSTRACT
BACKGROUND: The World Bank has reported that global smoking rates declined from 2000 to 2012, with the only exception found in males in Sub-Saharan Africa. Sub-Saharan Africa is considered to be in stage one of the tobacco epidemic continuum. To address this problem, school-based programs for smoking prevention are considered cost-effective and promising. Since tobacco prevention programs are influenced by social competence or customs of each country, tobacco prevention programs that have success in Western countries are not always effective in African countries. Therefore, the current study systematically reviewed relevant literature to examine the effects of these types of programs in African countries. METHOD: Online bibliographic databases and a hand search were used. We included the studies that examined the impact of school-based programs on preventing tobacco use in Africa from 2000 to 2016. RESULTS: Six articles were selected. Four were conducted in South Africa and two were performed in Nigeria. Four programs were systematically incorporated into annual curriculums, targeting 8th to 9th graders, while the other two were temporary programs. All programs were based on the hypothesis that providing knowledge and/or social skills against smoking would be helpful. All studies utilized smoking or polydrug use rates to compare outcomes before/after intervention. There were no significant differences between intervention and control groups in three studies, with the other three demonstrating only partial effectiveness. Additionally, three studies also examined change of knowledge/attitudes towards smoking as an outcome. Two of these showed significant differences between groups. CONCLUSION: All RCTs studies showed no significant change of smoking-rate by the intervention. The effectiveness of intervention was observed only in some sub-group. The cohort studies showed school-based interventions may be effective in improving knowledge and attitudes about smoking. However, they reported no significant change of smoking-rate by the intervention.
Subject(s)
Nicotiana , School Health Services/organization & administration , Smoking Prevention/organization & administration , Adolescent , Africa , Humans , MaleABSTRACT
BACKGROUND: Asymptomatic malaria can be observed in both stable endemic areas and unstable transmission areas. However, although much attention has been given to acute malaria infections, relatively little attention has been paid to asymptomatic malaria. Nonetheless, because the asymptomatic host serves as a reservoir for the malaria parasite, asymptomatic malaria is now recognized as an important obstacle to malaria elimination. Asymptomatic malaria is also associated with anaemia, a global public health problem with serious consequences on human health as well as social and economic development. In Lao People's Democratic Republic (Lao PDR), malaria, anaemia, and malnutrition are serious public health concerns. However, few studies have focused on the relationship between these variables. Therefore, this study investigated the relationship between asymptomatic malaria, growth status, and the prevalence of anaemia among children aged 120 months old or younger in rural villages in Lao PDR. METHODS: In December 2010 and March 2011, data were collected from five villages in Savannakhet province. Anthropometric measurements, blood samples, and malaria rapid diagnostic tests were conducted. The presence of malaria was confirmed with polymerase chain reaction assays for Plasmodium falciparum. Underweight status, stunting, and anaemia were defined according to World Health Organization standards. RESULTS: The mean age of participants (n = 319) was 88.3 months old (Standard Deviation: 20.6, ranged from 30-119 months old), and 20 participants (6.3 %) had an asymptomatic malaria infection, 92 (28.8 %) were anaemic, 123 (38.6 %) were underweight, and 137 (42.9 %) were stunted. Stunted children were more likely to be infected with asymptomatic malaria [odds ratio (OR) 3.34, 95 % confidence interval (CI) 1.25-8.93], and asymptomatic malaria was associated with anaemia [OR 5.17, 95 % CI 1.99-13.43]. CONCLUSIONS: These results suggest a significant association between asymptomatic malaria and anaemia in children. Furthermore, stunted children were more likely to have lower Hb levels and to be infected with asymptomatic malaria than children without stunting. However, further studies examining the impact of asymptomatic malaria infection on children's nutritional and development status are necessary.
Subject(s)
Anemia/complications , Anemia/epidemiology , Asymptomatic Diseases/epidemiology , Developmental Disabilities/epidemiology , Developmental Disabilities/etiology , Malaria, Falciparum/complications , Malaria, Falciparum/epidemiology , Anemia/etiology , Anthropometry , Blood/parasitology , Child , Child, Preschool , Clinical Laboratory Techniques , Cross-Sectional Studies , Female , Humans , Laos/epidemiology , Male , Plasmodium falciparumABSTRACT
In the last decade, a National School Health Policy (NSHP) has been formulated in several developing countries following the recommendations of the Global School Health Initiative. However, NSHP implementations across the country have not been fully shared. This study aimed to identify factors that have influenced implementation of the NSHP in Lao People's Democratic Republic (Lao PDR). We conducted key informant interviews with 20 NSHP implementers and document reviews. Data were collected at the national level and at three lower administrative levels (provincial, district and school) in three areas (north, central and south). Study areas were selected according to the history of NSHP interventions. We applied content analysis using 12 key components of successful policy implementation and a policy triangle framework. We found that scaling up to nationwide implementation was limited. Results showed the NSHP implementation in Lao PDR was influenced by nine interlinked factors, including extensive planning, resource management, monitoring cycle, the perception gap between national and lower administrative officers, national task-force ownership, ongoing coaching of district educational officers, management skills of school principals, priority of school health and decentralization. Furthermore, these nine factors could be integrated into the existing educational system. In conclusion, for sustainable and nationwide implementation of the NSHP in Lao PDR, the following three factors need to be embedded in the educational system: extensive planning with a clear long-term vision at national level, human resource management including well-organized training at each administrative level and a monitoring cycle to understand the real situation at school level.
Subject(s)
Health Plan Implementation/methods , Health Policy , School Health Services , Adult , Developing Countries , Humans , Interviews as Topic , LaosABSTRACT
BACKGROUND: In Tak province of Thailand, a number of adolescent students who migrated from Burma have resided in the boarding houses of migrant schools. This study investigated mental health status and its relationship with perceived social support among such students. METHODS: This cross-sectional study surveyed 428 students, aged 12-18 years, who lived in boarding houses. The Hopkins Symptom Checklist (HSCL)-37 A, Stressful Life Events (SLE) and Reactions of Adolescents to Traumatic Stress (RATS) questionnaires were used to assess participants' mental health status and experience of traumatic events. The Medical Outcome Study (MOS) Social Support Survey Scale was used to measure their perceived level of social support. Descriptive analysis was conducted to examine the distribution of sociodemographic characteristics, trauma experiences, and mental health status. Further, multivariate linear regression analysis was used to examine the association between such characteristics and participants' mental health status. RESULTS: In total, 771 students were invited to participate in the study and 428 students chose to take part. Of these students, 304 completed the questionnaire. A large proportion (62.8%) indicated that both of their parents lived in Myanmar, while only 11.8% answered that both of their parents lived in Thailand. The mean total number of traumatic events experienced was 5.7 (standard deviation [SD] 2.9), mean total score on the HSCL-37A was 63.1 (SD 11.4), and mean total score on the RATS was 41.4 (SD 9.9). Multivariate linear regression analysis revealed that higher number of traumatic events was associated with more mental health problems. CONCLUSIONS: Many students residing in boarding houses suffered from poor mental health in Thailand's Tak province. The number of traumatic experiences reported was higher than expected. Furthermore, these traumatic experiences were associated with poorer mental health status. Rather than making a generalized assumption on the mental health status of migrants or refugees, more detailed observation is necessary to elucidate the unique nature and vulnerabilities of this mobile population.
Subject(s)
Housing/statistics & numerical data , Mental Disorders/epidemiology , Social Support , Students/psychology , Adolescent , Child , Cross-Sectional Studies , Female , Humans , Life Change Events , Male , Myanmar/ethnology , Risk Factors , Surveys and Questionnaires , Thailand/epidemiologyABSTRACT
Experimental studies have indicated that low serum zinc levels affect immune responses. However, few studies have evaluated the impact of serum zinc levels on antibody responses in the field in developing countries. We investigated an association between the anti-Plasmodium falciparum (Pf) antibody (immunoglobulin G) titer and serum zinc concentration among villagers in rural areas of the Lao People's Democratic Republic. Blood samples were collected to detect Pf infection. An enzyme-linked immunosorbent assay (ELISA) was used to measure the anti-PfIgG antibody titer. Each serum sample was assayed to measure the concentration of zinc. Pearson's correlation coefficient was applied to the association between zinc concentration and anti-PfIgG antibody titers. Multiple linear regression analysis was used to assess the association between zinc concentration and anti-PfIgG antibody titers, controlling for age and albumin level. Of 71 blood samples, 40 were Pf positive and 31 were Pf negative. The median serum zinc concentrations were 56.0 µg/dl in the Pf-positive group and 62.5 µg/dl in the Pf-negative group. The median anti-Pf titers were 833.4 in the positive group and 1237.2 in the negative group. Unexpectedly, there was a negative correlation between serum zinc and anti-Pf IgG antibody titers; the correlation coefficient were -0.453 and (p=0.003) in the positive group and -0.461 (p=0.009) in the negative group. The results of this study indicated sustained antibody responses among the villagers, who had likely been exposed to malaria periodically throughout their lives. Further studies are necessary to determine the conditions in which zinc could be effective against malaria.
Subject(s)
Antibodies, Protozoan/blood , Plasmodium falciparum/immunology , Serum/chemistry , Serum/immunology , Zinc/blood , Adolescent , Adult , Child , Child, Preschool , Cross-Sectional Studies , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immunoglobulin G/blood , Laos , Male , Middle Aged , Rural Population , Young AdultABSTRACT
In Thailand, a health-promoting school (HPS) program is in place nationwide. However, this policy has not covered Burmese migrant schools. Therefore, to ensure the feasibility of the implementation of a HPS program, we conducted evaluations and an intervention on school health in migrant schools in Thailand. We included 44 primary-level schools in the Tak province in 2008. We were able to evaluate the results of the intervention in 43 of 44 schools in the subsequent year. For measurement, we used a comprehensive school-health checklist with five components: 'personal health and life skills', 'healthy school environment', 'health and nutrition services', 'common disease control and prevention', 'school and community partnership'. The checklist contained 59 items; item scores ranged from 0 to 3. We compared the results of the two surveys (performed before and after the intervention) by calculating the mean score of each item. A 1.3-fold increase was seen in the mean of all items measured in the evaluation (from 1.7 to 2.2, n= 43). Out of the five components, the greatest difference was detected in 'school and community partnership', which increased from 1.0 to 2.4. Notably, the mean score of item 4 of component 5, 'clear definition of the roles and responsibilities with the Burmese community', increased from 0.4 to 2.7. Although further study is necessary to investigate the association between our intervention and the improvements among schools, our school health evaluation and intervention were successfully implemented in Burmese migrant schools.
Subject(s)
School Health Services/organization & administration , Checklist , Child , Data Collection , Health Status , Humans , Myanmar/ethnology , School Health Services/standards , Schools/organization & administration , Thailand , Transients and MigrantsSubject(s)
Depression/psychology , Depression/rehabilitation , Work , Humans , Stress, Psychological/diagnosisABSTRACT
OBJECTIVE: Three of the us developed a new non-invasive continuous cardiac output (CCO) measurement method utilizing routine clinical monitors based on the pulse-contour analysis combined with pulse wave transit time (PWTT). Using pulmonary artery catheter (CCOpa), we compared this estimated CCO (esCO) with the thermodilution CCO early after cardiac surgery, and tested whether the esCO method has potential of being an alternative measure of CCO. METHODS: Thirty-six patients without continued arrhythmias were studied. esCO was computed using electrocardiogram (ECG) monitor, arterial pressure monitor and pulse-oximetry system. Both sets of data (esCO and CCOpa), by averaging the results of the preceding 10 min, were compared at 30-min intervals throughout the 15.8 +/- 3.3 h (S.D.) of study. Bland-Altman plots and correlation analysis were used for statistical comparison. RESULTS: A total of 981 paired sets of data (89.9%) among 1093 measurements were compared in the absence of displacement of either pulse-oximetry or ECG probes and/or inaccurate detection of R wave. The difference between esCO and CCOpa results was -0.06 +/- 0.82 L/min (S.D.), and there was a linear correlation between them (r = 0.80, p < 0.0001). The difference between them was 0.00 +/- 0.48 L/min at the first 1 h, which remained unchanged throughout 20 h after the start of measurement. CONCLUSIONS: The results demonstrate that esCO has a close correlation with the CCOpa, even though the two methods are not interchangeable. The results suggest that esCO method has potential of being an alternative non-invasive cardiac output trend, unless there are apparent arrhythmias.
Subject(s)
Cardiac Output , Pulse , Adult , Aged , Arrhythmias, Cardiac , Cardiovascular Surgical Procedures , Catheterization, Swan-Ganz , Electrocardiography , Female , Humans , Male , Middle Aged , Monitoring, Physiologic/methods , Sensitivity and Specificity , ThermodilutionABSTRACT
Ceramide is formed through sphingomyelin hydrolysis or de novo synthesis and may play a key role in cell growth, differentiation and apoptosis. To clarify which pathway tumor cells use to form ceramide and how its formation is regulated, we determined the levels of dihydroceramide and ceramide in mice inoculated with Sarcoma 180, B16 melanoma or Lewis lung carcinoma cells. The levels in these tumor masses were very high compared to those in other healthy tissues. The high levels were significantly reduced by a single administration of the dihydroceramide synthase inhibitor fumonisin B(1), but not by a sphingomyelinase inhibitor, sphingomyelin analog-1 (SMA-1), suggesting that the tumor cells have a very effective means of synthesizing dihydroceramide and ceramide. To investigate the characteristics of dihydroceramide synthase, we prepared microsomes from Sarcoma 180 tumor masses and healthy mouse liver cells, and compared their catalytic activities on dihydroceramide formation. A kinetic analysis using sphinganine and palmitoyl CoA as substrates revealed that the enzyme present in the tumor formed dihydroceramide 3 times more efficiently than that in healthy liver cells. Partial purification of dihydroceramide synthase from bovine liver microsomes revealed that the enzyme was present in healthy tissues as a 333 kDa form constructed of 47 kDa subunit proteins. However, gel filtration of the enzyme solubilized from the Sarcoma 180 tumor masses demonstrated that its molecular weight was 1300 kDa. These results suggest that malignant transformation causes the cell to produce a form of dihydroceramide synthase with a larger than normal molecular mass; the increased molecular mass may account for the enzyme's increased catalytic efficiency.
Subject(s)
Amides/metabolism , Ceramides/metabolism , Microsomes/enzymology , Organophosphonates/metabolism , Oxidoreductases/physiology , Animals , Apoptosis , Catalysis , Cattle , Ceramides/pharmacology , Chromatography, Gel , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Fumonisins/pharmacology , Gene Expression Regulation, Enzymologic , Kinetics , Liver/enzymology , Liver Neoplasms/enzymology , Male , Melanoma, Experimental , Mice , Mice, Inbred C57BL , Mice, Inbred ICR , Microsomes, Liver/enzymology , Oxidoreductases/metabolism , Tumor Cells, CulturedABSTRACT
A series of short-chain analogues of N-palmitoylsphingosine-1-phosphate, modified by replacement of the phosphate and the long alkenyl side chain with hydrolytically stable difluoromethylene phosphonate and phenyl, respectively, were prepared to study the structure-activity relationship for inhibition of sphingomyelinase. The study revealed that inhibition is highly dependent upon the stereochemistry of the asymmetric centers of the acylamino moiety, and resulted in identification of a non-competitive inhibitor with the same level of inhibitory activity of schyphostatin, the most potent of the few known small molecular inhibitors of sphingomyelinase.