Possible role of metal ionophore against zinc induced cognitive dysfunction in <Emphasis Type="SmallCaps">d-</Emphasis>galactose senescent mice

Metal ionophores are considered as potential anti-dementia agents, and some are currently undergoing clinical trials. Many metals are known to accumulate and distribute abnormally in the aging brain. Alterations in zinc metal homeostasis in the glutaminergic synapse could contribute to ageing and the pathophysiology of Alzheimer’s disease (AD). The present study was designed to investigate the effect of metal ionophores on long term administration of zinc in D-galactose induced senescent mice. The ageing model was established by combined administration of zinc and D-galactose to mice for 6 weeks. A novel metal ionophore, PBT-2 was given daily to zinc-induced d-galactose senescent mice. The cognitive behaviour of mice was monitored using the Morris Water Maze. The anti-oxidant status and amyloidogenic activity in the ageing mouse was measured by determining mito-oxidative parameters and deposition of amyloid β (Aβ) in the brain. Systemic administration of both zinc and D-galactose significantly produced memory deficits, mito-oxidative damage, heightened acetylcholinesterase enzymatic activity and deposition of amyloid-β. Treatment with PBT-2 significantly improved behavioural deficits, biochemical profiles, cellular damage, and curbed the deposition of APP in zinc-induced senescent mice. These findings suggest that PBT-2, acting as a metal protein attenuating compound, may be helpful in the prevention of AD or alleviation of ageing.     

Differential regulation of the brain and gut immunoreactive dynorphin by the serotonin system

Administration of drugs such as fenfluramine, 20-40 mg/kg, and m-chlorophenylpiperazine (m-CPP), 2.5-5 mg/kg, which release serotonin or activate postsynaptic serotonin receptors, respectively, induced a dramatic decrease in the duodenal content of immunoreactive dynorphin (ir-DYN). The effect was antagonized by cyproheptadine, 1 mg/kg. Similarly, acute administration of the specific serotonin reuptake blockers fluvoxamine, 15 mg/kg, or femoxetine, 10 mg/kg, and 5-hydroxytryptophan (5-HTP), 40-160 mg/kg, evoked a marked decrease in the duodenal content of ir-DYN. A combined administration of fluvoxamine or femoxetine and 5-HTP failed to potentiate the effect of individual treatment. Only a higher dose of fenfluramine, 40 mg/kg, increased the ir-DYN content in the hypothalamus. These results suggest that the brain and gut ir-DYN is independently regulated by the serotonin system and that a serotonin mechanism might stimulate release of the gut dynorphin content.     

Continuous production of galacto-oligosaccharides from lactose using immobilized β-galactosidase from Bacillus circulans

Summary -Galactosidase-2 (-d-galactoside galactohydrolase, EC 3.2.1.23) from Bacillus circulans was purified using hydroxyapatite gel chromatography and immobilized onto Duolite ES-762 (phenolformaldehyde resin) and Merckogel (controlled pore silica gel) for continuous production of galacto-oligosaccharides using lactose as the substrate. The maximum amount of ologosaccharides produced by the immobilized enzyme was 35–40% of the total sugar during hydrolysis of 4.56% lactose. Partially purified -galactosidase from B. circulans was also immobilized onto various supports for the same purpose. The stability of the immobilized -galactosidase-2 or partially purified enzyme during a continuous reaction depended on their supports and specific activity. Of the supports tested, Merckogel was best for operational stability. With this support, the enzyme was quite stable with specific activity up to 15 units/g of wet gel; it was reversibly inactivated with more.     

Histopathology of retained bovine fetal membranes

Placentomes were obtained from 20 cows with retained placenta (9 following normal birth, 5 after abortion and 6 with dystocia), and this material was examined by light microscopy. Histologic changes that were consistently seen in placentomes of cows with retained placenta after normal birth included vascular changes (edema, thrombosis and vasculitis) and the presence of numerous clumps of bacterialcolonies in the connective tissue of the caruncles and cotyledons. Only a few binucleate cells were seen in these cases. In placentomes obtained from cows with retained placenta after abortion, there were instances of focal necrosis of the fetal villi and the presence of variable numbers of binucleate cells. Vascular changes and numerous clumps of bacterial colonies in the caruncles and cotyledons were also noted. The changes in placentomes obtained from cows with retained placenta and dystocia included the presence of numerous binucleate cells, infiltration of polymorphonuclear cells in the connective tissue of both the fetal and maternal villi, vascular changes, and the presence of extensive necrosis and numerous clumps of bacterial colonies. Significant differences (P < 0.05) were encountered in the number of binucleate cells in the various groups. Binucleate cells appear to be involved in the process of placental separation in cows with retained placenta.     

Using patient and general practice characteristics to explain variations in cervical smear uptake rates.

OBJECTIVES--To produce practice and patient variables for general practices from census and family health services authority data, and to determine the importance of these variables in explaining variation in cervical smear uptake rates between practices. DESIGN--Population based study examining variations in cervical smear uptake rates among 126 general practices using routine data. SETTING--Merton, Sutton, and Wandsworth Family Health Services Authority, which covers parts of inner and outer London. MAIN OUTCOME MEASURE--Percentage of women aged 25-64 years registered with a general practitioner who had undergone a cervical smear test during the five and a half years preceding 31 March 1992. RESULTS--Cervical smear uptake rates varied from 16.5% to 94.1%. The estimated percentage of practice population from ethnic minority groups correlated negatively with uptake rates (r = -0.42), as did variables associated with social deprivation such as overcrowding (r = -0.42), not owning a car (r = -0.41), and unemployment (r = -0.40). Percentage of practice population under 5 years of age correlated positively with uptake rate (r = 0.42). Rates were higher in practices with a female partner than in those without (66.6% v 49.1%; difference 17.5% (95% confidence interval 10.5% to 24.5%)), and in computerised than in non-computerised practices (64.5% v 50.5%; 14.0% (6.4% to 21.6%)). Rates were higher in larger practices. In a stepwise multiple regression model that explained 52% of variation, five factors were significant predictors of uptake rates: presence of a female partner; children under 5; overcrowding; number of women aged 35-44 as percentage of all women aged 25-64; change of address in past year. CONCLUSIONS--Over half of variation in cervical smear uptake rates can be explained by patient and practice variables derived from census and family health services authority data; these variables may have a role in explaining variations in performance of general practices and in producing adjusted measures of practice performance. Practices with a female partner had substantially higher uptake rates.     

Molecular cloning and analysis of CDC28 and cyclin homologues from the human fungal pathogen Candida albicans

In the budding yeast Saccharomyces cerevisiae, progress of the cell cycle beyond the major control point in G1 phase, termed START, requires activation of the evolutionarily conserved Cdc28 protein kinase by direct association with GI cyclins. We have used a conditional lethal mutation in CDC28 of S. cerevisiae to clone a functional homologue from the human fungal pathogen Candida albicans. The protein sequence, deduced from the nucleotide sequence, is 79% identical to that of S. cerevisiae Cdc28 and as such is the most closely related protein yet identified. We have also isolated from C. albicans two genes encoding putative G1 cyclins, by their ability to rescue a conditional GI cyclin defect in S. cerevisiae; one of these genes encodes a protein of 697 amino acids and is identical to the product of the previously described CCN1 gene. The second gene codes for a protein of 465 residues, which has significant homology to S. cerevisiae Cln3. These data suggest that the events and regulatory mechanisms operating at START are highly conserved between these two organisms.     

Enterotoxigenic aeromonads on retail lamb meat and offal

Enrichment in alkaline peptone water was compared with the direct plating method for the isolation of Aeromonas spp. from lamb meat and offal samples. The enrichment method significantly increased the isolation rate of aeromonads. Motile Aeromonas species (A. hydrophila, A. sobria and A. caviae) were present in all kinds of samples investigated. Seventy-three Aeromonas strains isolated in this survey were characterized to species level and examined for their ability to produce virulence factors. Strains identified as A. sobria were the strongest producers of haemolysin and enterotoxin, whereas A. caviae strains were consistently non-haemolytic and non-enterotoxigenic. Thus it is likely that lamb meat and offal are potentially significant sources of virulent Aeromonas species and may play an important role in the aetiology of Aeromonas-associated gastro-enteritis.     

Deprivation payments to general practitioners: limitations of census data.

The census data from which deprivation payments have been calculated since June 1995 suffer from limitations including underenumeration; under counting of homeless people and refugees, and artefactual errors because of the way in which the 1991 census data were tabulated. These limitations reduced the fairness of the changes that many practices experienced in their deprivation payments. The validity of the current system of deprivation payments would be improved if these limitations were borne in mind when allocating payments to practices and if enumeration districts were used as the basis of payments rather than electoral wards.     

The Cerebral Neurosecretory System,Secretory End-Foot System and Infracerebral Gland—a Probable Neuroendocrine Complex in Nephtys (Annelida; Polychaeta)

Abstract The brain of Nephtys contains four neurosecretory cell types with distinctive cytoplasmic inclusions, a cells are located uniquely in a single pair of ganglionic nuclei and b cells are represented by a single pair of cells, whereas c cells and d cells have a scattered distribution. Their axons form two types of secretory release structure. First, possible axon collaterals synapse upon slender “dentritic twigs” in the core of the brain. Secondly, two tracts descend to the brain floor to form a “neurosecretory neuropile” (or storage and release complex) in contact with the inner surface of the brain capsule. Other neurosecretory fibres penetrate through the capsule, branch extensively, and terminate in contact with its ventral surface in close association with the “infracerebral gland”. The gland is derived from the pericapsular epithelium and exhibits signs of specialization for glandular function. In contrast to certain other polychaetes, it does not contain secretory neuron perikarya. The secretory end-foot system is poorly developed. Its terminals are located adjacent to the neurosecretory neuropile, which they encircle. The cell bodies are probably represented by four e cells which, like the terminals, contain many mitochondria.