Raccoon roundworm (Baylisascaris procyonis) encephalitis: case report and field investigation.

Baylisascaris procyonis is a common and widespread parasite of raccoons in the United States and Canada. With large raccoon populations occurring in many areas, the potential risk of human infection with B procyonis is high. We report a case of severe raccoon roundworm (B procyonis) encephalitis in a young child to illustrate the unique clinical, diagnostic, and treatment aspects, as well as public health concerns of B procyonis infection. Acute and convalescent serum and cerebrospinal fluid samples from the patient were tested for antibodies against B procyonis to assist in documenting infection. An extensive field survey of the patient's residence and the surrounding community was performed to investigate raccoon abundance and to determine the extent of raccoon fecal contamination and B procyonis eggs in the environment. The patient evidenced serologic conversion, and the field investigation demonstrated a raccoon population far in excess of anything previously reported. There was abundant evidence of B procyonis eggs associated with numerous sites of raccoon defecation around the patient's residence and elsewhere in the community. Because B procyonis can produce such severe central nervous system disease in young children, it is important that pediatricians are familiar with this infection. The public should be made aware of the hazards associated with raccoons and B procyonis to hopefully prevent future cases of B procyonis infection.

Diclofenac sodium (Voltaren) reduced exercise-induced injury in human skeletal muscle.

PURPOSE: To examine the effects of prolonged systemic administration of diclofenac sodium (Voltaren), a nonsteroidal anti-inflammatory drug, on objective indices of exercise-induced muscle damage in humans. METHODS: Fifty-four volunteers (mean age, 26.4 yr; range, 18-35) participated in this randomized double-blind, placebo-controlled trial. To achieve steady-state tissue levels, either placebo or diclofenac was orally administered two times a day for 27 consecutive days. A strenuous 20-min stepping exercise program, about which the subjects were unfamiliar, was conducted on day 15. Creatine kinase (CK) activities were measured immediately before the exercise session and on days 16, 18, and 27. Vastus lateralis muscle samples were obtained immediately before exercise and on day 27 for subsequent histological characterization of muscle inflammation. RESULTS: The preexercise muscle samples revealed no difference in muscle damage between the two groups. However, the postexercise muscle samples showed that the diclofenac-treated group demonstrated less muscle tissue damage than placebo-treated subjects (P = 0.002). The administration of diclofenac also resulted in a significant lowering of post-/pre-exercise CK ratios on days 18 (P = 0.03) and 27 (P = 0.02) compared with the placebo group, an indirect finding that supports the possibility of diclofenac reducing exercise-induced muscle damage. CONCLUSION: These findings demonstrate preadministration of diclofenac (in accordance with tissue half-life pharmacokinetics) significantly reduces quantitative indices of exercise-induced skeletal muscle damage in human muscle.

Type IV pili, transient bacterial aggregates, and virulence of enteropathogenic Escherichia coli.

Type IV bundle-forming pili of enteropathogenic Escherichia coli are required for the localized adherence and autoaggregation phenotypes. Whether these pili are also required for virulence was tested in volunteers by inactivating bfpA or bfpT (perA) encoding, respectively, the pilus subunit and the bfp operon transcriptional activator. Both mutants caused significantly less diarrhea. Mutation of the bfpF nucleotide-binding domain caused increased piliation, enhanced localized adherence, and abolished the twitching motility-dispersal phase of the autoaggregation phenotype. The bfpF mutant colonized the human intestine but was about 200-fold less virulent. Thus, BfpF is required for dispersal from the bacterial aggregate and for full virulence.

Long-term administration of heparin and heparin fractions and osteoporosis in experimental animals.

To test whether heparin-induced osteoporosis is influenced by the molecular weight of heparin, 24 male rabbits received single daily subcutaneous injections of either physiological saline (controls, n = 5), low molecular weight heparin (LMWH, n = 7), conventional heparin (UFH, n = 7) or high molecular weight heparin (HMWH, n = 6). Heparin was administered in supratherapeutic daily dosages for 120 days (750 anti-FXa units/kg for 90 days and 1500 anti-FXa units/kg for another 30 days). Studied variables were: serial analysis of serum calcium, albumin, phosphate and alkaline phosphatase, measurement of the cortical thickness of the femur (radiographically), tibial and trabecular bone density (both by cross-sectional analysis) and femoral fragility. Observed changes in blood biochemistry associated with bone metabolism were not correlated to any of the treatments. Compared with the controls, a reduction in cortical and trabecular bone density was seen with UFH (P < 0.05) and HMWH (P < 0.01) but not with LMWH. Femoral fragility was also significantly increased (P < 0.002) by HMWH. In conclusion, LMWH did not cause toxic skeletal effects as opposed to HMWH which clearly did, and UFH which induced some osteoporotic changes.

Organization and targets of the prior informed consent notification scheme. Part I. Development and implementation.

The concern about the trade in chemicals has led to the development and adoption of the International code of conduct on the distribution and use of pesticides by the Food and Agriculture Organization of the United Nations (FAO) and the London guidelines for the exchange of information on chemicals in international trade by the United Nations Environment Programme (UNEP). Both codes are voluntary, are addressed largely to governments and industry, and incorporate both practical guidelines and ethical considerations. To ensure the implementation of this principle a prior informed consent (PIC) procedure has been established, which operates in addition to the broader information exchange and export notification provisions. The goal of PIC is to create an international system whereby participating importing countries will obtain information concerning chemicals whose use has been banned or severely restricted in other countries, decide whether to allow, restrict or prohibit future import of such chemicals, and notify other countries on a formal basis of their decision concerning such imports. Exporting countries are then expected to inform their export industry of these decisions and take steps within their authority to ensure that their export industry does not make shipments contrary to the decisions of participating importing countries. A Joint FAO/UNEP group of experts on PIC has been established to develop and provide guidance on the implementation of the PIC procedure.

Cloning and characterization of the bundle-forming pilin gene of enteropathogenic Escherichia coli and its distribution in Salmonella serotypes.

bfp, the structural gene of the major repeating bundle-forming pilus (BFP) subunit, was cloned from the enteroadherent factor (EAF) plasmid of enteropathogenic Escherichia coli (EPEC) strain B171 (O111:NM). The bfp open reading frame encoded a 193-amino-acid protein; comparison of this sequence with the biochemically determined N-terminal amino acid sequence showed that the mature pilin protein is comprised of 180 amino acids, that this sequence is similar to other members of the type IV pilin family, and that it is preceded by a 13-amino-acid signal peptide. Expression of the cloned bfp structural gene in an EPEC strain that had been cured of the EAF plasmid yielded a 21,000 dalton protein that co-migrated with the BFP precursor protein. Thus, other genes, probably carried by the EAF plasmid, are required for the maturation of the bfp product and for the production of extracellular pilus filaments. Use of bfp as a hybridization probe showed that homologous sequences are present in all tested EPEC strains and in 13 of 16 tested Salmonella serotypes. Fifty per cent of these bfp probe-sensitive salmonellae exhibited the localized-adherence (LA) phenotype when incubated with tissue culture cell monolayers, a trait previously associated with EAF plasmid-containing EPEC strains. Scanning electron micrographs of a bfp probe-sensitive, LA-positive Salmonella dublin strain showed that it grows as adherent colonies on infected monolayers and that within these colonies, BFP-like fibres form inter-bacterial linkages. For EAF plasmid-containing EPEC strains and for several Salmonella serotypes, BFP expression may lead to the development of adherent colonies on epithelial surfaces early in the infective process.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced decrease in the fluidity of rat liver membranes.

1. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCCD)-induced lipid peroxidation has previously been demonstrated by assessing the hepatic content of thiobarbituric acid reactive substances (TBARS) as well as the NADPH-dependent microsomal formation of TBARS as well as the NADPH-dependent microsomal formation of TBARS using malondialdehyde as the standard. 2. Changes in membrane fluidity as a result of lipid peroxidation may occur. Therefore the dose- and time-dependent effects of TCDD on lipid peroxidation in mitochondrial, microsomal, and plasma membranes, and changes in membrane fluidity in these subcellular fractions, were examined. Animals were treated with either 50 or 100 micrograms TCDD/kg orally, and killed 3, 6, or 9 days post-treatment. 3. Time-dependent increases occurred in TBARS content and formation following TCDD administration for all three membranes. Similar results were observed after 50 and 100 micrograms TCDD/kg. 4. Following TCDD administration, fluorescence polarization measurements as determined by the fluorescence polarization (r) and anisotropy parameter (a.p.) values demonstrated significant decreases in membrane fluidity in all membrane fractions, indicative of membrane structural alterations. 5. Excellent inverse correlations between lipid peroxidation and membrane fluidity were observed. Thus, decreased membrane fluidity and increased membrane damage may contribute to the toxic manifestations of TCDD as a consequence of an oxidative stress.

Hepatic lipid peroxidation, sulfhydryl status, and toxicity of the blue-green algal toxin microcystin-LR in mice.

Microcystin-LR (MCLR), a cyclic heptapeptide produced by the blue-green algae Microcystis aeruginosa, produces death in female mice treated with 100 micrograms MCLR/kg. Kupffer-cell hyperplasia was observed histologically after treatment with 50 or 100 micrograms MCLR/kg. No other changes or lethality were observed with the 50 micrograms MCLR/kg, while 100% lethality occurred in less than 2 h in mice treated with 100 micrograms/kg. In these animals liver weights increased by 45% and hepatic hemoglobin content increased 106% at 60 min posttreatment. Liver histology showed loss of hepatic architecture and necrosis 30 min after treatment, and congestion with blood became evident at 45 min after treatment. Serum enzymes were significantly increased 45 min posttreatment. Hepatic nonprotein sulfhydryl content decreased 19% when calculated on the basis of cytosolic protein and 39% when based upon the total protein content, respectively. The sulfhydryl content of the liver cytoskeletal fraction decreased 26% by 30 min after treatment. Decreased enzyme-mediated and increased non-enzyme-mediated lipid peroxidation were observed in hepatic microsomes following both in vivo and in vitro exposure of hepatic microsomes to MCLR. The toxicity of MCLR may be related to alterations in the sulfhydryl content of the cytoskeletal protein. Furthermore, MCLR may either directly or indirectly affect microsomes, suggesting alterations in structure and function of smooth endoplasmic reticulum.

Desferrioxamine-induced alterations in hepatic iron distribution, DNA damage and lipid peroxidation in control and 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated rats.

Desferrioxamine (DFX), an iron chelator, has been used to inhibit in vitro redox cycling of the transition iron irons that may interfere with free-radical formation, and is used clinically to treat conditions associated with iron overload. The effect of DFX on hepatic iron distribution has not been examined. Therefore, we have examined the effect of DFX on iron content and distribution, lipid peroxidation and DNA single-strand breaks in liver. Since 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) enhances hepatic lipid peroxidation and induces DNA damage, the ability of DFX to modulate these effects was also examined. Female Sprague-Dawley rats received 200 mg DFX kg-1 i.p. every 12 h for 10 days and 50 micrograms TCDD kg-1 p.o. on Day 4 as a single dose. All animals were killed 7 days after TCDD administration. The results demonstrate that DFX alone did not decrease hepatic iron content, but enhanced the iron distribution in mitochondria, microsomes and nuclei. A 10-day administration of DFX resulted in enhanced hepatic lipid peroxidation and DNA single-strand breaks, consistent with the alterations in iron distribution. TCDD administration produced large increases in lipid peroxidation in microsomes, nuclei and whole-liver homogenates, as well as enhanced DNA damage. However, the marked increases in lipid peroxidation produced by TCDD were attenuated by DFX, while the DNA damaging effects of TCDD and DFX were additive.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparative effects of pair-feeding and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on various biochemical parameters in female rats.

Hypophagia is a common characteristic of the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and may be responsible for some of the toxic manifestations. Pair-feeding has been used in control animals to compensate for the hypophagia, but relatively few studies have assessed biochemical changes associated with pair-feeding versus weight loss induced by TCDD. Rats were treated with TCDD and killed 7 days post-treatment while pair-fed animals received an amount of diet equivalent to TCDD-treated partner animals. Ad libitum-fed rats were also used. No correlations were seen in altered calcium and iron homeostasis between pair-feeding and TCDD administration relative to ad libitum-fed animals. Pair-feeding resulted in greater alterations than TCDD administration in the subcellular distribution of iron in mitochondria, microsomes and cytosol. Pair-feeding also resulted in greater accumulation of calcium in mitochondria and microsomes in pair-fed as compared to TCDD-treated animals. Greater lipid peroxidation was observed in whole liver and nuclei of rats receiving TCDD relative to pair-fed animals. A significantly greater incidence of DNA single strand breaks occurred in hepatic nuclei of TCDD-treated animals as compared to pair-fed and ad libitum-fed animals. Significantly greater inhibition of hepatic glutathione peroxidase activity and thymic involution were observed in TCDD treated animals as compared to the pair-fed group. Although some similarities existed between TCDD-treated animals and pair-fed rats, the overall biochemical changes which were observed following TCDD administration cannot be attributed to weight loss associated with hypophagia.

Factors influencing the induction of DNA single strand breaks in rats by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

The ability of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to induce lipid peroxidation and DNA damage in rat hepatic nuclei was investigated. In addition, the role of iron in hepatic DNA damage was examined. Female Sprague-Dawley rats were treated with a single dose of 25--100 micrograms TCDD/kg orally, and sacrificed 3-14 days after treatment. Liver nuclei were isolated, and DNA single strand breaks (DNA-SSB) and lipid peroxidation were determined. Lipid peroxidation was assessed by measuring the content and production of thiobarbituric acid reactive substances (TBARS) while DNA-SSB were determined by the alkaline elution technique. The results demonstrate that TCDD dose and time-dependent increases in hepatic nuclear TBARS content and production occur in conjunction with an increase in DNA-SSB. The administration of the dithiolthione antioxidant oltipraz (30 mg/kg/day for 10 days) resulted in a significant decrease (47%) in the incidence of TCDD-induced DNA-SSB. Clofibrate administration (100 mg/kg/day for 12 days) and pair feeding had no effect on TCDD-induced DNA-SSB. The incubation of hepatic microsomes and mitochondria from TCDD-treated rats with nuclei from untreated animals for one hr at 37 degrees C resulted in enhanced DNA damage which was abolished by the addition of 0.10 mM desferrioxamine (DFX). Incubation with cytosol had no significant effect. Incubation of 0.10 mM Fe2+ or Fe3+ with isolated hepatic nuclei from untreated rats produced significant increases in DNA-SSB, which were abolished by the addition of 0.10 mM DFX to the incubation medium. TCDD may produce an increased bioavailability of iron which leads to enhanced DNA single strand breaks and lipid peroxidation in hepatic nuclei.

Radiolabeled 9- or 10-monoiodostearic acid and 9- or 10-monoiodostearyl carnitine--I. Synthesis and purification.

The purpose of this investigation was to synthesize and purify radiolabeled 9- or 10-monoiodostearyl carnitine for potential use as a perfusion and metabolic imaging agent for the heart. Oleic acid was iodinated via a free radical addition reaction of HI across the double bond to give 9- or 10-monoiodostearic acid which in turn was esterified with carnitine. The identity of 9- or 10-monoiodostearic acid and 9- or 10-monoiodostearyl carnitine was determined using nuclear magnetic resonance (NMR), infrared (i.r.), ultraviolet (u.v.), and mass spectroscopy. The purity of the fatty acid and carnitine ester was established by thin layer chromatography. 9- or 10-Monoiodo[125I]stearic acid and 9- or 10-monoiodo[125I]stearyl carnitine were synthesized via the isotopic exchange of 125I for cold iodine bonded to 9- or 10-monoiodostearic acid and 9- or 10-monoiodostearyl carnitine.

Double-blind comparison of nalbuphine and meperidine in combination with diazepam for intravenous conscious sedation in oral surgery outpatients.

Nalbuphine and meperidine were compared as analgesic components of intravenous conscious sedation in a double-blind, prospective trial of 47 patients undergoing elective oral surgery. Subjects were evaluated for pain intensity, pain relief, anxiety, sedation, recall, and vital signs at systematic observation points intraoperatively and postoperatively. At the conclusion of surgery 83% of patients who had received nalbuphine and 86% of patients treated with meperidine indicated complete pain relief. One observed adverse reaction was attributed to meperidine and another to the sedative component diazepam. No statistically significant differences were observed between nalbuphine and meperidine treatments.

Biochemical and functional effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the heart of female rats.

Biochemical, functional and morphologic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the hearts of female rats were examined. Six days after the treatment of rats with TCDD, the blood pressures and resting heart rates were significantly less than in control animals. Treated animals were also less responsive to the effects of the beta-1 agonist, (-)isoproterenol. No histopathologic changes were observed in the heart although extensive centrilobular necrosis occurred in the liver after TCDD administration. Serum levels of thyroxine were 66% less than in control animals. Marked lipid peroxidation was produced in the liver with small but significant increases occurring in the heart. TCDD administration had no effect on catalase activity in the heart, but produced a 20% decrease in superoxide dismutase activity relative to control animals. The effects of TCDD on cardiac function do not appear to be due to a direct action of the xenobiotic on the heart but possibly to a down-regulation of beta-receptors in the heart as a result of the hypothyroid state.