Support for the hypothesis that metallothionein isoforms participate in intracellular defense against reactive oxygen and nitrogen species is derived from observations that substances causing oxidative stress, such as ethanol and iron, and agents involved in inflammatory processes, such as interleukin-1 and tumour necrosis factor alpha, induce the synthesis of metallothionein. Moreover, animals deficient in metallothionein isoforms exhibit greater susceptibility to oxidative stress; metallothionein genes are transcriptionally activated in cells and tissues during oxidative stress; and over expression of metallothionein reduces the sensitivity of cells and tissues to free radical-induced injury. In this study, we have shown that the i.
View Article and Find Full Text PDFNeurotoxicology
January 1997
Oxidative stress, resulting either from excess generation or reduced scavenging of free radicals, has been proposed to play a role in damaging striatal neurons in Parkinson's disease. Since metallothionein is able to regulate the intracellular redox potential, we have undertaken a group of experiments to learn whether or not 6-hydroxydopamine, which generates free radicals and is toxic to dopaminergic neurons, could alter the levels of zinc and metallothionein in the brain. The lesioning of the rat striatum with 6-hydroxydopamine (8.
View Article and Find Full Text PDF1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a neurotoxin that induces parkinsonism in human and non-human primates. Its mechanism of action is not fully elucidated. Recently, the participation of trace metals, such as manganese, on its neurotoxic action has been postulated.
View Article and Find Full Text PDFEur J Biochem
September 1995
Northern-blot analysis of RNAs from different tissues demonstrated that the mRNA for the protein kinase CK2 alpha subunit is very abundant in the ovary of Xenopus laevis. The competitive reverse-PCR technique has been used to quantitate the mRNA for both CK2 alpha and CK2 beta subunits during oogenesis. The results obtained using eight different animals consistently show an increment of 2-3-fold in the mRNA for both subunits in vitellogenic oocytes (stages II-VI).
View Article and Find Full Text PDFMany, but not all, zinc-containing neurons in the brain are a subclass of the glutamatergic neurons, and they are found predominantly in the telencephalon. These neurons store zinc in their presynaptic terminals and release it by a calcium-dependent mechanism. These "vesicular" pools of zinc are viewed as endogenous modulators of ligand- and voltage-gated ion channels.
View Article and Find Full Text PDFPharmacol Toxicol
June 1995
The mechanism of action of MPTP, a parkinsonism-inducing drug has been related to trace metals as a result of the observed potentiation of the neurotoxic action of the drug when diethyldithiocarbamate is concurrently administered. Diethyldithiocarbamate is a well-known chelator of trace metals, particularly copper. In the present study we analyzed the concentrations of copper and manganese in four brain regions of mice treated with neurotoxic doses of MPTP, in order to further substantiate the relationship between trace metals of MPTP-induced neurotoxicity.
View Article and Find Full Text PDFProc West Pharmacol Soc
January 1995
Pharmacol Toxicol
June 1993
Mice received different doses intracerebroventricularly of MPP+ (1-methyl-4-phenylpyridinium ion), the active metabolite of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a drug which induces a Parkinson model in rodents. Two indexes of lipid peroxidation were monitored at different times after administration: 1) production of thiobarbituric acid-reactive substances and 2) formation of lipid fluorescence products. A regional-selective overproduction of thiobarbituric acid-reactive substances was observed in corpus striatum and midbrain, but not in frontal cortex, cerebellum nor hippocampus.
View Article and Find Full Text PDFProc West Pharmacol Soc
October 1993
We report on an infant with multiple congenital anomalies and mosaic trisomy 8 [corrected]. Clinical findings are presented, and compared with those of the 24 cases previously reported. Some unusual characteristics found in this patient include macrocephaly, an extreme degree of palatal hypoplasia, and abnormally shaped long bones.
View Article and Find Full Text PDFProc West Pharmacol Soc
September 1992
In a previous report of a zinc supplementation trial in pregnant adolescents zinc effect varied according to maternal weight (wt) status--normal (90-110% of expected wt), light or heavy, prompting this analysis of effects of wt status and gestational wt gain on fetal heaviness relative to length and gestational age (GA) and other pregnancy outcomes. One-third of adolescents shifted in or out of normal wt by delivery, creating seven outcome groups--light-light, light to normal, normal to light, normal-normal, normal to heavy, heavy to normal, and heavy-heavy. These wt class change groups varied significantly as to intrauterine growth (SGA, low AGA, high AGA, and LGA); by weekly grams gain per cm height (ht), birth wt, infant wt/length ratio, and occurrence of low birth wt (LBW).
View Article and Find Full Text PDFTo identify the symptoms and coexisting medical conditions associated with idiopathic intracranial hypertension (IIH), we administered an 83-item questionnaire at the time of diagnosis to 50 IIH patients and 100 aged-matched controls. Ninety percent of the IIH patients were women; the mean age was 33. Obesity and recent weight gain were much more common among patients than controls.
View Article and Find Full Text PDFProgress in bringing health care to the workplace lags considerably behind progress in bringing health care to where people live. Experience in Botswana shows that the family nurse practitioner--a registered nurse midwife with one year of post-basic training--can provide useful preventive and curative services to people in their places of work.
View Article and Find Full Text PDFIn a double-blind zinc trial in low-income, pregnant adolescents thought to be at risk for poor zinc nutriture, subjects were randomly assigned to receive 30 mg zinc (gluconate) or placebo. Response to zinc was related to maternal weight. Infants of normal-weight mothers given zinc had reduced rates of prematurity (p = 0.
View Article and Find Full Text PDFWe examined the in-vitro activity of 12 antibiotics against Gram-negative bacillary isolates from 141 distinct episodes of nosocomial bloodstream infection occurring from July 1984 through November 1986. At least ten strains of each of the seven most frequently encountered species were tested. Relative potency was carefully assessed by extending the concentrations from 0.
View Article and Find Full Text PDFSample size determination for case-control studies of chronic disease are often based on the simple 2 X 2 tabular cross-classification of exposure and disease, thereby ignoring stratification which may be considered in the analysis. One consequence of this approach is that the sample size may be inadequate to attain a specified power and size when performing a statistical analysis on J 2 X 2 tables using Cochran's (1954, Biometrics 10, 417-451) statistic or the Mantel-Haenszel (1959, Journal of the National Cancer Institute 22, 719-748) statistic. A sample size formula is derived from Cochran's statistic and it is compared with the corresponding one derived when the data are treated as unstratified, and also with two other formulas proposed for stratified data analysis.
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