Purification and Characterization of Cinnamoyl-Coenzyme A:NADP Oxidoreductase in Eucalyptus gunnii.

Cinnamoyl-coenzyme A:NADP oxidoreductase (CCR, EC 1.2.1.44), the entry-point enzyme into the monolignol biosynthetic pathway, was purified to apparent electrophoretic homogeneity from differentiating xylem of Eucalyptus gunnii Hook. The purified protein is a monomer of 38 kD and has an isoelectric point of 7. Although Eucalyptus gunnii CCR has approximately equal affinities for all possible substrates (p-coumaroyl-coenzyme A, feruloyl-coenzyme A, and sinapoyl-coenzyme A), it is approximately three times more effective at converting feruloyl-coenzyme A than the other substrates. To gain a better understanding of the catalytic regulation of Eucalyptus CCR, a variety of compounds were tested to determine their effect on CCR activity. CCR activity is inhibited by NADP and coenzyme A. Effectors that bind lysine and cysteine residues also inhibit CCR activity. As a prerequisite to the study of the regulation of CCR at the molecular level, polyclonal antibodies were obtained.

Adolescents with myelodysplasia: impact of physical disability on emotional maturation.

Certain physical, psychological and social characteristics of 20 adolescents with myelodysplasia are compared to those of age and gender-matched controls. In addition to the obvious physical differences the areas of greatest concern are self-esteem and social-sexual adjustment. Family relations, feelings, and modes of expression were not different in the two groups. Lack of appropriate chores, decreased opportunities to interact and compete with peers, plus uncertainties to interact and compete with peers, plus uncertainties about bowel and bladder continence appear to be the greatest impediments to emotional growth in this physically handicapped group of teenagers. Early recognition of such problems and finding strategies to overcome them are important aspects of the comprehensive care of any person with a chronic disability.

Bayesian forecasting of gentamicin pharmacokinetics in pediatric intensive care unit patients.

The predictive performance of a one compartment Bayesian forecasting program was evaluated in pediatric intensive care unit patients with normal renal function. Gentamicin pharmacokinetic parameters were determined in 44 PICU patients (0.8 month to 14 years old) from all available serum concentrations and doses by nonlinear least squares regression. Population pharmacokinetic parameter estimates were established from 27 of the PICU patients. Mean prediction error (ME) and mean absolute error (MAE) for 2 future sets of peak and trough gentamicin serum concentrations with the use of the population parameter estimates with and without feedback were evaluated in the remaining 17 patients. Mean clearance (+/- SD) and volume of distribution for all 44 patients were 0.123 +/- 0.041 liter/hour/kg and 0.424 +/- 0.116 liter/kg, respectively. Bayesian forecasting of the second set of peak and trough concentrations with feedback from the first set of peak and trough concentrations resulted in smaller bias (peak ME, -0.15 mg/liter; trough ME, 0.13 mg/liter) and better accuracy (peak MAE, 0.91 mg/liter; trough MAE, 0.28 mg/liter) compared with the population parameter estimates alone (peak ME, 0.4 mg/liter; trough ME, 0.28 mg/liter; peak MAE, 1.21 mg/liter; trough MAE, 0.57 mg/liter). This study indicates that gentamicin volume of distribution in PICU patients is larger than non-PICU literature values. The Bayesian program, with specific population parameter estimates for PICU patients, provides accurate initial and subsequent predictions of gentamicin serum concentrations.

Evaluation of universal hepatitis B immunization practices of Illinois pediatricians.

OBJECTIVE: To characterize universal hepatitis B immunization practices of pediatricians who routinely provide childhood immunizations in Illinois. DESIGN: Survey of 522 randomly chosen Illinois pediatricians. Student's t test, chi 2 analysis, and multivariate logistic regression were used to identify relationships between physician demographics and outcomes of interest. MAIN OUTCOME MEASURES: Physician agreement with the new Centers for Disease Control and Prevention Immunization Practices Advisory Committee and the American Academy of Pediatrics universal infant hepatitis B immunization guidelines, incorporation of the recommendations, routine hepatitis B immunization of older children (aged 6 months to 11 years), and routine hepatitis B immunization of adolescents. RESULTS: The survey response rate was 71.5%. Of those pediatricians routinely providing immunizations (N = 323), 72.8% agreed with and 90.1% have incorporated universal hepatitis B immunization; 36.5% and 53.0% routinely immunized older children and adolescents, respectively. Pediatricians practicing in medium-sized practices were half as likely to agree with the recommendations (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.31 to 0.84). Cost and a belief that universal immunization of infants is not medically necessary were the two most commonly listed reasons for not incorporating the new guidelines. Percent reimbursement from public aid was negatively related to the routine immunization of older children (OR, 0.34; 95% CI, 0.12 to 0.95). Both percent reimbursement from self-pay (OR, 5.62; 95% CI, 2.25 to 14.05) and a rural location (OR, 0.16; 95% CI, 0.04 to 0.56) were related to routine hepatitis B immunization of adolescents. Gender and number of years in practice were not associated with physician response. CONCLUSIONS: The majority of Illinois pediatricians who routinely provide pediatric immunizations have incorporated the new universal hepatitis B immunization guidelines into their practices. Continued efforts to address financial barriers and to educate physicians may hasten the time when the transmission of the hepatitis B virus will no longer occur.

Structure-activity studies with fragments and analogous of salmonid melanin-concentrating hormone.

A number of cyclic and linear fragments and analogues of MCH were synthesized and their biological potencies tested using the isolated carp scale melanophore assay. In this system the cyclic portion MCH(5-14) exhibited only 0.1% bioactivity, which was markedly enhanced by the addition of the exocyclic sequences MCH(15-17) and MCH(1-4). The exocyclic sequence itself, MCH(1-4,15-17), had minimal activity, however. Substitution of Tyr11 with phenylalanine reduced the potency of the ring structure MCH(5-14) by about 4-fold. Substitution of Gly8 with D-alanine reduced the potency of MCH(5-14) 16-fold, while both substitutions together caused a still more marked reduction (200-fold) in bioactivity. Linearized fragments of MCH, extending from MCH(15-17) to [Cys(Acm)5,14]MCH(1-17), showed a progressive increase in potency. The linearized forms of MCH, MCH(5-17) and MCH(5-14), were approximately 100-fold or less potent than their cyclic forms. The significant increases in bioactivity produced by the addition of the C- and N-terminal exocyclic sequence even to these linearized forms further emphasizes the importance of these regions for interaction at the receptor site.

Pachyderms, primates, plants and population.

In the past, growth in human population has often been associated with species loss. Current rates of population growth, both globally (1 million more births than deaths every 103 hours) and regionally, pose a threat of additional ecological damage. There is a well-documented unmet demand for family planning in nearly all high-fertility countries. Improved family planning and safe abortion services will improve the health of women and their families, accelerate fertility decline, and help preserve the environment. Many ecologically vulnerable areas are especially poorly served by family planning services. Examples are given here of improving family planning services through private health providers near the Kakamega Forest in western Kenya, and of adding family planning choices to a reforestation project run by the Jane Goodall Institute near the Gombe National Park, Tanzania. Wildlife biologists can play a critical role in identifying local professionals and institutions with the potential to improve family planning.

Aluminum toxicity in a molluscan neuron: effects of counterions.

Previous studies using the freshwater snail Lymnaea stagnalis have indicated significant accumulation of aluminum (Al) from simple salts (chloride or nitrate) or Al lactate [Al(lactate)3 preparations, but not from the Al maltol complex [Al(maltol)3]. This is in contrast to findings in mammalian systems, where uptake and neurotoxicity are greatest for the soluble and lipophilic Al(maltol)3 complex. This study was undertaken to investigate the direct effects of extracellular Al (100 microM) from three Al preparations [AlCl3, Al(lactate)3 and Al(maltol)3] on electrophysiological parameters of an identified neuron, the right parietal dorsal 1 (RPD1) neuron, of L. stagnalis in vitro. The effects of the corresponding counterion/ligand on the solubility and availability of Al in solution were also examined. Significant effects of Al on electrical properties, including membrane depolarization, increased firing activity, and abnormal firing patterns, were seen in the presence of AlCl3 and Al(lactate)3, which formed polyhydroxy and labile Al species in aqueous solution, but not with Al(maltol)3, which remained as the soluble monomeric complex. Qualitative differences were also observed between the response to AlCl3 and Al(lactate)3, despite their similar chemistry. The extent of action potential broadening was greater with Al(lactate)3, suggesting some interaction between Al and lactate in their cellular uptake and/or toxicity. It is suggested that polyhydroxy Al species are toxic to molluscan neurons, possibly via disruption of intracellular Ca2+ homeostasis.

Preparation of dipeptoid mimetics for the tetrapeptide cholecystokinin, CCK(30-33).

The diastereoselective synthesis of 2,3-methanophenylalanine methyl esters (5) has been achieved in 58% yield. The preparation of the dehydropeptides (1, R = Me; 2, R = H) and the cyclopropylpeptides (3, R = Me; 4, R = H) possessing good binding affinities for the CCK-A and CCK-B receptors is described. Conformational studies of the dipeptide esters 1 and 3 indicated the presence of a beta-turn within the peptide backbone, although there was no preference in type. The Phe and Trp moieties, however, did prefer to be situated on the same side of the peptide turn which is favourable for receptor binding.

Citrinin toxicity in growing chicks.

Male broiler chicks, from day-old to 3 weeks of age, were fed diets containing 0, 100, 220, 330, and 440 ppm citrinin produced by Penicillium lanosum grown on whole corn. Body weight decreased (P less than .05) when chicks were fed the diets containing 330 and 440 ppm citrinin. Average body weight of chicks fed the diet containing 220 ppm citrinin was 8% less than that of chicks fed no toxin. Feed utilization decreased (P less than .05) with chicks fed the diet containing 440 ppm citrinin. Analysis of thigh muscle, kidney, liver, and blood for citrinin revealed detectable amounts in the liver and blood of chicks fed 440 ppm.

Bioaccumulation and toxicity of aluminium in the pond snail at neutral pH.

The low solubility of aluminium (Al) at neutral pH means that it largely exists as colloidal particulates in aquatic systems. However, the pond snail Lymnaea stagnalis accumulates significant amounts of Al following exposure to water containing added Al (up to 500 microg l(-1)) at pH 7. This is accompanied by depression of behavioural activity (locomotion, feeding) which subsequently recovers, suggesting tolerance to the metal. The presence of silica ameliorates behavioural toxicity of Al, but does not prevent uptake of the metal. In vitro studies using the isolated central nervous system demonstrate toxicity at the cellular level. Extracellular application of Al (100 microM) led to membrane depolarisation, bursts of action potentials and action potential broadening. The chemical form in which Al is applied influences the extent of bioaccumulation and toxicity. Detailed knowledge of its solution chemistry is therefore essential.

Sexual dysfunction: A systematic review of South African research.

BACKGROUND: The World Health Organization is in the process of revising the International Classification of Diseases and Related Health Problems (ICD). Sexual dysfunction disorders (F52) have been identified as having poor clinical utility. South Africa (SA) has been selected as one of five low- and middle-income countries in which studies will be developed to assess the clinical utility of the proposed ICD-11 revisions for sexual dysfunction disorders. OBJECTIVE: To identify scientific research generated in SA on sexual dysfunction disorders to guide these studies. METHODS: A systematic review of SA research on sexual dysfunction disorders published in peer-reviewed journals. RESULTS: Despite the high prevalence of ejaculatory and erectile dysfunctions, only five SA articles have addressed male sexual dysfunction since 1970. Lack of sexual interest and inability to reach orgasm are the most commonly reported complaints for women, yet only four SA articles have been published on the topic of female sexual dysfunction. Diabetes mellitus, cardiovascular disease, genitourinary disease and psychiatric or psychological disorders are common comorbid conditions associated with sexual dysfunction in both sexes, but only nine articles address sexual dysfunction as the main topic with respect to comorbid conditions. CONCLUSION: Despite growing awareness of the importance of sexual health, SA-based scientific research on sexual dysfunction is limited. Further work is needed to inform recommendations for ICD-11 revisions drawn from the SA context.