Pharmacokinetic Model to Describe the Lymphatic Absorption of r-metHu-Leptin After Subcutaneous Injection to Sheep

Purpose. The purpose of this work was to develop a pharmacokinetic model to describe the contribution of the lymphatics to the absorption and bioavailability of r-metHu-Leptin administered by subcutaneous (SC) injection to sheep. Methods. r-metHu-Leptin was administered either by bolus intravenous injection (0.1 mg/kg) into the jugular vein or by SC injection (0.15 mg/kg) into the interdigital space of the hind leg. The SC groups included a non-cannulated control group and a lymph-cannulated group, in which peripheral lymph was continuously collected from a cannula in the efferent popliteal lymph duct. Serum and lymph concentrations were determined by enzyme-linked immunosorbent assay and profiles were modeled using compartmental pharmacokinetic methods. The fraction of the dose reaching the systemic circulation (F _sys) and the proportions of the absorbed dose taken up via the blood (F _blood) and lymph (F _lymph) were determined. Results. Serum and lymph concentration vs. time profiles were well described by a two compartment model with parallel first order absorption into blood and lymph. F _sys for the SC control group was 60.4 ± 8.4%. In the lymph-cannulated group, 21.7 ± 6.4% of the dose was recovered in serum and 34.4 ± 9.7% was recovered in peripheral lymph giving a total fraction absorbed (F _abs) of 56.0 ± 10.3%. F _sys for the SC control group was not significantly different to F _abs in the lymph-cannulated group. Conclusion. This study has shown that the lymph represents the predominant pathway for absorption of r-metHu-Leptin after SC administration.     

Early termination of breast-feeding in periurban Santo Domingo, Dominican Republic: mothers' community perceptions and personal practices.

OBJECTIVES: The objectives of this study were to determine: 1) whether mothers' perceptions of typical community practice for breast-feeding duration influence their personal practices and 2) whether the mothers' reports of community reasons for terminating breast-feeding identify barriers not elicited through self-report. METHODS: The study was conducted in 1997 in a sample of poor neighborhoods in a periurban district of Santo Domingo, the capital of the Dominican Republic. A representative sample of 220 mothers from these neighborhoods was interviewed with a structured questionnaire. RESULTS: While the duration of breast-feeding was similar for self-report and for mothers' perceptions of typical community practice, there was no statistically significant correlation between these two variables. "Mother-driven" reasons for early termination of breast-feeding, such as "fear of loss of figure or of breast shape" and "not wanting to breast-feed," were frequently perceived as community reasons but rarely given as personal reasons. Personal reasons were predominately "child-driven," including "the child not wanting the breast," or reasons beyond the mother's control such as having "insufficient" milk. CONCLUSIONS: Maternal report of community reasons for early termination may be a useful way to identify factors that would not otherwise be revealed on self-report. These additional reasons may guide health promotion efforts aimed at increasing breast-feeding duration.     

2-Amino-5-phosphonovalerate and Co2+ selectively block depolarization and burst firing of rat hippocampal CA1 pyramidal neurones by N-methyl-D-aspartate

Intracellular recordings from pyramidal neurones during microiontophoretic ejection of N-methyl-D-aspartate and quisqualate into the pyramidal cell layer of the CA1 region of the rat hippocampal slice showed that both amino acids caused depolarization and evoked spike activity. Whereas quisqualate evoked tetrodotoxin-sensitive spikes, those produced by N-methyl-D-aspartate consisted of bursts of tetrodotoxin-sensitive action potentials superimposed on an underlying depolarizing shift of membrane potential. Both membrane depolarization and the superimposed depolarizing shifts associated with N-methyl-D-aspartate excitation were selectively and reversibly antagonized by the D(-) isomer of 2-amino-5-phosphonovalerate and Co2+. Both amino acids caused an increase in membrane conductance when small ejection currents were used, and the depolarizing response to these compounds was prevented by current injection. However, only the increase by N-methyl-D-aspartate was blocked by 2-amino-5-phosphonovalerate and Co2+. These results provide evidence to support the suggestion that different mechanisms underlie the excitatory response to N-methyl-D-aspartate and quisqualate in CA1 pyramidal neurones.     

PROGRAM EVALUATION AND SERVICE MONITORING IN VICTORIAN COMMUNITY HEALTH CENTRES

This paper reports a survey of program evaluation and service monitoring activity in 49 Victorian community health centres. Centres generally have not made evaluation and monitoring an important part of their operations despite the rhetoric of health services policy makers and administrators. Reasons for this include a lack of staff in centres who are trained in evaluation methods; the reluctance of centre staff to divert time and resources from service provision to evaluation; and insufficient assistance to centres from the Health Commission of Victoria. “The assumptions that operating a service is equivalent to rendering service and that both are equivalent to rendering quality service are no longer being honoured as inherently valid.”¹     

Listen carefully: The risk of error in spoken medication orders

Clinicians and patients often confuse drug names that sound alike. We conducted auditory perception experiments in the United States to assess the impact of similarity, familiarity, background noise and other factors on clinicians' (physicians, family pharmacists, nurses) and laypersons' ability to identify spoken drug names. We found that accuracy increased significantly as the signal-to-noise (S/N) ratio increased, as subjective familiarity with the name increased and as the national prescribing frequency of the name increased. For clinicians only, similarity to other drug names reduced identification accuracy, especially when the neighboring names were frequently prescribed. When one name was substituted for another, the substituted name was almost always a more frequently prescribed drug. Objectively measurable properties of drug names can be used to predict confusability. The magnitude of the noise and familiarity effects suggests that they may be important targets for intervention. We conclude that the ability of clinicians and lay people to identify spoken drug names is influenced by signal-to-noise ratio, subjective familiarity, prescribing frequency, and the similarity neighborhoods of drug names.     

A school-based obesity control programme: Project Energize. Two-year outcomes

Chokeberries are a rich source of anthocyanins, which may contribute to the prevention of obesity and the metabolic syndrome. The aim of the present study was to determine if an extract from chokeberries would reduce weight gain in rats fed a fructose-rich diet (FRD) and to explore the potential mechanisms related to insulin signalling, adipogenesis and inflammatory-related pathways. Wistar rats were fed a FRD for 6 weeks to induce insulin resistance, with or without chokeberry extract (CBE) added to the drinking-water (100 and 200 mg/kg body weight, daily: CBE100 and CBE200). Both doses of CBE consumption lowered epididymal fat, blood glucose, TAG, cholesterol and LDL-cholesterol. CBE consumption also elevated plasma adiponectin levels and inhibited plasma TNF-α and IL6, compared with the control group. There were increases in the mRNA expression for Irs1, Irs2, Pi3k, Glut1, Glut4 and Gys1, and decreases in mRNA levels of Gsk3β. The protein and gene expression of adiponectin and Pparγ mRNA levels were up-regulated and Fabp4, Fas and Lpl mRNA levels were inhibited. The levels of gene expression of inflammatory cytokines, such as Il1β, Il6 and Tnfα were lowered, and protein and gene expression of ZFP36 (zinc finger protein) were enhanced in the epididymal adipose tissue of the rats that consumed the CBE200 extract. In summary, these results suggest that the CBE decreased risk factors related to insulin resistance by modulating multiple pathways associated with insulin signalling, adipogenesis and inflammation.     

Effect of laser in situ keratomileusis for hyperopia on tear film and ocular surface

PURPOSE: To examine the effects of laser in situ keratomileusis (LASIK) for hyperopia on the tear film and ocular surface. METHODS: A retrospective 12-month analysis of 88 eyes (88 participants) who had LASIK for hyperopia was performed. Participants were evaluated before and after (2 weeks, 1, 3, 6, and 12 months) surgery for dry eye symptoms (McMonnies Dry Eye Survey primary symptoms), tear film stability (fluorescein break-up time), tear volume (phenol red thread test), ocular surface staining (fluorescein), and conjunctival goblet cell density. RESULTS: Chronic dry eye was experienced by 32% of participants; symptoms were significantly associated with female gender, preoperative dry eye symptoms, lower tear film stability after surgery, greater ocular surface staining after surgery, lower tear volume before and after surgery, and lower goblet cell densities after surgery. Regression rate 12 months after surgery was 32% and significantly associated with female gender, chronic dry eye symptoms, lower tear film stability after surgery, greater ocular surface staining before and after surgery, and lower tear volume before and after surgery. CONCLUSIONS: Dry eye, particularly in females, is problematic after LASIK for hyperopia and is associated with refractive regression. Current methods for managing the tear film and ocular surface may not control LASIK-induced dry eye, particularly in some females during the first 6 months after surgery.