Maintenance of growth in cystic fibrosis despite reduction in pancreatic enzyme supplementation

Twenty one children with cystic fibrosis were advised to decrease their pancreatic enzyme supplement (PES) dose to less than 10,000 units lipase/kg/day. Mean PES dosage was significantly decreased in 15 patients from 18,380 to 8647 units lipase/kg/day. There were no significant changes in energy or fat intake, but there were significant increases in weight SD score, height SD score, and weight/height ratio.     

Morphogenetic roles of acetylcholine

In the adult nervous system, neurotransmitters mediate cellular communication within neuronal circuits. In developing tissues and primitive organisms, neurotransmitters subserve growth regulatory and morphogenetic functions. Accumulated evidence suggests that acetylcholine, (ACh), released from growing axons, regulates growth, differentiation, and plasticity of developing central nervous system neurons. In addition to intrinsic cholinergic neurons, the cerebral cortex and hippocampus receive extensive innervation from cholinergic neurons in the basal forebrain, beginning prenatally and continuing throughout the period of active growth and synaptogenesis. Acute exposure to ethanol in early gestation (which prevents formation of basal forebrain cholinergic neurons) or neonatal lesioning of basal forebrain cholinergic neurons, significantly compromises cortical development and produces persistent impairment of cognitive functions. Neonatal visual deprivation alters developmental expression of muscarinic acetylcholine receptors (mAChR) in visual cortex, whereas local infusion of mAChR antagonists impairs plasticity of visual cortical neurons. These findings raise the possibility that exposure to environmental neurotoxins that affect cholinergic systems may seriously compromise brain development and have long-lasting morphologic, neurochemical, and functional consequences.     

serotonin immunocytochemistry in the adult and developing rat brain: Methodological and pharmacological considerations

An antiserum has been raised in rabbits against serotonin (5-HT) conjugated to the invertebrate protein hemocyanin (HC). This antiserum was characterized with respect to its cross-reactivity with related compounds and its immunocytochemical staining properties in brains of adult and developing rats and in animals pretreated with various pharmacological regimens. When compared to an antiserum raised against 5-HT/bovine serum albumin (BSA) conjugates [59], the 5-HT/HC conjugate elicited a more profound immune response which resulted in the production of a specific, high titer antiserum that could be used directly for immunocytochemistry without removal of antibodies to the invertebrate carrier molecule, HC. Immunoabsorption experiments to assess the specificity of this antiserum demonstrated a small degree of cross-reactivity with dopamine (which was greater than that with norepinephrine or epinephrine). However, no staining of catecholaminergic neurons was found in untreated adult or developing animals, nor in animals pretreated with L-DOPA or L-DOPA + the MAO inhibitor nialamide, indicating that this cross-reactivity is not manifested under normal staining conditions. No cross-reactivity of the 5-HT/HC antiserum was observed for any 5-HT precursors or metabolites tested, although both this antiserum and the 5-HT/BSA antiserum did exhibit a high degree of cross-reactivity to the related indoleamines 5-methoxytryptamine (5-MT) and tryptamine. However, based on the immunocytochemical staining patterns observed, and the fact that both 5-MT and tryptamine are found in very low quantities in the normal rat brain, it appears that 5-HT is the predominent indoleamine stained by both of these antisera in the untreated rat brain. In animals pretreated with L-tryptophan + nialamide, some light staining was found in the dopaminergic A9 and A10 cell groups using either antiserum. However, since this staining was not observed in L-DOPA + nialamide treated animals it is not thought to be due to cross-reactivity with dopamine. Rather, since the staining could be inhibited by pretreatment with the catecholaminergic uptake blocker desmethylimipramine, it is postulated that this effect may be due to either

1. (1) the non-specific uptake of 5-HT or 5-hydroxytryptophan (5-HTP) into the dopaminergic cells of A9 and A10 due to elevated levels of these substances in the dense serotonergic axonal plexus passing through this region.

2. (2) to an increased uptake of circulating L-tryptophan by these A9 and A10 cells followed by conversion of this amino acid to tryptamine by aromatic amine decarboxylase, an enzyme common to both 5-HT and dopaminergic neurons. This latter possibility suggests that caution should be exercised when interpreting immunocytochemical staining patterns obtained in animals pretreated with L-tryptophan + nialamide using 5-HT antisera, since other cross-reactive indoleamines could be elevated by this pharmacological manipulation.

Prevalence and time trends in obesity among adult West African populations: a meta-analysis

The objective of this study was to determine the distribution of and trends in obesity in adult West African populations.
Between February and March 2007, a comprehensive literature search was conducted using four electronic databases. Journal hand searches, citations and bibliographic snowballing of relevant articles were also undertaken. To be included, studies had to be population-based, use well-defined criteria for measuring obesity, present data that allowed calculation of the prevalence of obesity and sample adult participants. Studies retrieved were critically appraised. Meta-analysis was performed using the DerSimonian-Laird random effect model.
Twenty-eight studies were included. Thirteen studies were conducted in urban settings, 13 in mixed urban/rural and one in rural setting. Mean body mass index ranged from 20.1 to 27.0 kg². Prevalence of obesity in West Africa was estimated at 10.0% (95% CI, 6.0–15.0). Women were more likely to be obese than men, odds ratios 3.16 (95% CI, 2.51–3.98) and 4.79 (95% CI, 3.30–6.95) in urban and rural areas respectively. Urban residents were more likely to be obese than rural residents, odds ratio 2.70 (95% CI, 1.76–4.15). Time trend analyses indicated that prevalence of obesity in urban West Africa more than doubled (114%) over 15 years, accounted for almost entirely in women.
Urban residents and women have particularly high risk of overweight/obesity and obesity is rising fast in women. Policymakers, politicians and health promotion experts must urgently help communities control the spread of obesity in West Africa.     

Liver tumours following streptozotocin administration in rats and the effects of pancreatic islet cell transplantation

The effects of a single injection of streptozotocin, at a dosageof 50 mg/kg body weight, have been studied in female inbredWAG rats. The resultant diabetes in the streptozotocin treatedanimals was treated in one group of animals by an intraportalpancreatic islet cell transplantation whilst another group receivedno transplant or insulin treatment. The incidence of tumourswas determined at autopsy in animals sacrificed at regular intervals.Tumours, apart from one renal adenocarcinoma, were seen onlyin the liver and only in streptozotocin treated animals. Livernodules and cysts were most common in animals which had receivedboth streptozotocin and an islet cell transplant.     

Cytochrome P4502D6 (debrisoquine 4-hydroxylase) and Parkinson''s disease in Chinese and Caucasians

Four polymorphic sites (C/T188, C/T2938, G/C4268, G/A1934) in the cytochrome P4502D6 (debrisoquine 4-hydroxylase) gene were investigated for their association with sporadic Parkinson's disease (PD). Three mutant alleles (C/T188, C/T2938 and G/C4268) result in amino acid changes which could alter the substrate specificity or alter its ability to metabolize their substrates; the fourth (G/A1934) causes a loss of enzyme activity. The study was carried out in two ethnically homogenous populations: Chinese (123 PD patients, 124 controls); and Caucasian (95 PD patients, 62 controls). Haplotype status, which took into account amino acid changes at three polymorphic sites, was deduced from genotyping results in order to investigate whether substrate specificity was important rather than loss of enzyme activity. There was no gender difference in the distribution of the alleles in either race. There was, however, significant association among the three polymorphic sites (C/T188, C/T2938, G/C4268) in both ethnic groups. T/T188:C/C2938:C/C4268 is the most common genotype in the Chinese population, in contrast to C/C188:C/T2938:C/G4268 (followed by C/C188:C/C2938:G/G4268) in Caucasians. All 69 of the sub-group of Chinese patients tested were homozygous for the wild-type allele at the G/A1934 polymorphic site. Neither the CYP2D6 allele nor haplotype was associated with PD in either ethnic group.