Balance of prostacyclin and thromboxane in offspring of parents with premature coronary arterial disease.

6-keto-prostaglandin F1a and thromboxane B2 were determined in order to obtain more information about the prostacyclin synthesis and thromboxane A2 release in 3- to 18-year-old healthy children and in offspring of parents who have had an acute myocardial infarction before the age of 45. The authors demonstrated a reduction of plasma prostacyclin synthesis in children with a positive family history of premature coronary arterial disease. Thromboxane levels in the affected adolescent boys were significantly lower compared with the controls. The ratio of thromboxane:prostacyclin in endangered children did not show a significant difference from that of healthy controls. These data indicate that prostaglandins are a definitive marker for identifying cardiovascular risk children. It must be supposed that in adolescence, only in boys, with a positive family history of premature coronary arterial disease, a compensatory mechanism exists to protect them from developing an imbalance in the regulation of prostaglandins.     

Synthesis and structure-activity relationships of new 9-N-alkyl derivatives of 9(S)-erythromycylamine

A series of new 9-N-alkyl derivatives of 9(S)-erythromycylamine has been synthesized by reductive alkylation of erythromycylamine with aliphatic aldehydes and sodium cyanoborohydride. Alternative syntheses employing hydrogenation methods have also been developed. These new 9-N-alkyl derivatives possess excellent antimicrobial activity in vitro and in vivo, especially when administered orally to treat experimental infections in mice. From structure-activity studies, 9-N-(1-propyl)erythromycylamine (LY281389) was selected as the most efficacious derivative. These methods have also been extended to the synthesis of some 9-N,N-dialkyl derivatives of erythromycylamine.     

Immunology

A selection of interesting papers that were published in the two months before our press date in major journals most likely to report significant results in immunology.     

Substance use among runaway and homeless youth in three national samples.

OBJECTIVES: Standardized estimates of the prevalence of substance use by runaway and homeless youth between the ages of 12 and 21 in various settings were compared with each other and with estimates for youth in the general population. METHODS: Four surveys were used: (1) a nationally representative survey of runaway and homeless youth residing in federally and non-federally funded shelters; (2) a multicity survey of street youth; (3) a nationally representative household survey of youth with and without recent runaway and homeless experiences; and (4) a nationally representative household survey of youth whose previous runaway/homeless status was unknown. RESULTS: For almost every substance, substance use prevalence was highest among street youth. Shelter youth and household youth with recent runaway/homeless experiences reported similar rates. In the household surveys, substance use rates were lowest and were generally comparable. CONCLUSIONS: Many homeless and runaway youth use tobacco, alcohol, and other drugs at rates substantially higher than nonrunaway and nonhomeless youth, indicating a need for comprehensive and intensive substance abuse prevention and treatment services for these youth.     

Access to primary health care for Australian young people: service provider perspectives.

BACKGROUND: To adequately address the complex health needs of young people, their access to services, and the quality of services received, must be improved. AIMS: To explore the barriers to service provision for young people and to identify the training needs of primary healthcare service providers in New South Wales (NSW), Australia. DESIGN OF STUDY: A cross-sectional, qualitative study of the perspectives of a range of health service providers. SETTING: A range of primary healthcare organisations across NSW. METHODS: Samples of general practitioners (GPs), youth health workers, youth health coordinators, and community health centre staff were drawn from urban and rural clusters across NSW. Focus groups and interviews were used to identify barriers to service provision and the training needs of service providers. Data were tape recorded, transcribed, and analysed. RESULTS: Barriers to service provision among GPs and community health centre staff included inadequate time, flexibility, skills, and confidence in working with young people, and poor linkages with other relevant services. Training needs included better knowledge of and skills in adolescent health requirements, working with adolescents, and working with other services. Barriers to service provision for youth health workers and coordinators included lack of financial resources and infrastructure. There were few linkages between groups of service providers. CONCLUSION: Models of service provision that allow stronger linkages between service providers, sufficient time for consultation with young people, adequate training and support of health professionals, and flexibility of service provision, including outreach, should be explored and evaluated.     

Pharmacokinetics of peptide T in patients with Acquired Immunodeficiency Syndrome (AIDS)

1. The pharmacokinetics of Dalal-peptide T-NH2 (peptide T) was determined during phase I clinical trials in patients with acquired immunodeficiecy disease (AIDS) and AIDS related complex (ARC). Drug levels were determined by specific RIA, and in some cases with HPLC analysis, after intraveneous (i.v.) or intranasal (i.n.), via metered sprayer, administration.

2. The plasma kinetics appeared to be bi-phasic with a first compartment half-life of 30 to 60 minutes and a second plasma clearence rate of 4 to 6 hours, observed for both routes of administration. Peptide T, in one individual was confirmed to be present at 6 hrs in plasma, determined after HPLC isolation followed by specific RIA.

3. Bioavailabilty, determined for a 2 mg test dose in six individuals was 9.3 ± 6.9 nmol/L. Peak plasma levels of 41 ± 30 nmol/L after 10 mg i.n., 2.8 ± 5.9 nmol/L after 2mg i.n., and 0.13 ± 0.07 nmol/L after 0.4 mg i.n. were observed. In two individuals tested, peptide T was detected in CSF at levels 20% of the corresponding plasma level 90 and 145 minutes post i.v. administration. Peptide T was not detected in urine. I.N. administration was well tolerated for times up to 21 months.