Cadmium toxicity and distribution in metallothionein-I and -II deficient transgenic mice

To date, numerous correlative studies have implicated metallothionein in the detoxification of heavy metals and in the regulation of metal distribution within an organism. In the present study cadmium-binding proteins (metallothionein equivalents), cadmium acute toxicity, and cadmium distribution in tissues and subcellular fractions were compared in metallothionein-I and -II deficient (MT-/-) mice and the parental strain carrying intact metallothionein genes (MT+/+) to determine if the absence of metallothionein altered any of these parameters. In an uninduced state, MT-/- mice expressed lower levels of cadmium-binding proteins relative to MT+/+ mice in several tissues. Administration of zinc enhanced the levels of cadmium-binding proteins in liver, small intestine, kidney, pancreas, and male sex organs, but not in cecum or brain of MT+/+ mice compared to zinc pretreated MT-/- mice. The cadmium LD50 was similar for MT-/-, MT+/+, and zinc-pretreated MT-/- mice (15-17 mumol CdCl2/kg body weight delivered i.p.). However, zinc-pretreated MT+/+ mice had a cadmium LD50 of 58-63 mumol CdCl2/kg body weight. Over two-thirds of cadmium was found in liver, cecum, small intestine, and kidney in both MT+/+ and MT-/- mice; therefore, metallothionein levels do not appear to play a major role in the tissue distribution of cadmium. However, after zinc pretreatment, MT+/+ mice accumulated more cadmium in the liver and less in other tissues, whereas the amount of cadmium in the liver was not altered by zinc pretreatment in MT-/- mice. In general, the cytosolic/particulate ratio of cadmium was significantly higher in tissues of noninduced MT+/+ mice relative to MT-/- mice. This difference was accentuated after zinc pretreatment. Together these results indicate that basal levels of metallothionein do not protect from the acute toxicity of a single i.p. cadmium challenge. Furthermore, it does not appear that the cytosolic compartmentalization of cadmium is correlated with reduced toxicity.     

Acute pulmonary edema caused by ingestion of hydrochlorothiazide

Hydrochlorothiazide is one of most commonly prescribed antihypertensive diuretics. In this case, an allergic reaction to hydrochlorothiazide resulted in severe pulmonary edema. Hydrochlorothiazide, one of the most commonly prescribed drugs, is a diuretic which is usually well tolerated. Common side effects include dizziness, weakness, fatigue, and cramps. These side effects are usually caused by fluid and electrolyte imbalances. Acute pulmonary edema, first reported by Steinberg in 1968, is a rare but potentially life-threatening allergic reaction to hydrochlorothiazide. This case illustrates many of the typical presenting features of the reaction.     

Xenon effects on regional cerebral blood flow assessed by 15O-H2O positron emission tomography: implications for hyperpolarized xenon MRI

Subjective and physiologic effects of 33% inhaled Xe were measured with 15O-water positron emission tomography (PET) in 3 subjects at rest and during visual stimulation. The procedure was well tolerated. Robust functional activations of the visual cortex were obtained after xenon (Xe) inhalation as well as air breathing. However, Xe inhalation was followed by smaller size, but significant decreases of regional cerebral blood flow (rCBF) in visual cortex relative to the air-breathing baseline, both during visual stimulation and at rest. No such decreases were found in other sensory or motor regions.     

Ursodeoxycholic acid improves the hepatic metabolism of essential fatty acids and retinol in children with cystic fibrosis

An ELISA sandwich for the detection of Giardia lamblia antigens in human faeces was standardized. 175 samples were studied: 77 positive, 61 negative to cysts and/or trophozoites by direct faeces test, and 19 positive to other parasite different from G. lamblia. The sensitivity of the technique was 94.8% and the specificity 98.3%. The method detects an antigen concentration of 31 ng. The procedure is simple, sensitive and specific so, it may be useful for diagnosis and in epidemiological studies.     

Studies of the expression of the Wiskott-Aldrich syndrome protein

The Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by thrombocytopenia, eczema, disorders in cell-mediated and humoral immunity, and a proclivity to lymphoproliferative disease. The gene responsible encodes a 53-kD proline-rich protein of unknown function (WASP). We produced a FLAG-WASP fusion protein that was used to immunize mice and produce mAbs against WASP. Using monoclonal anti-WASP in Western immunoblots, we have determined that WASP is present in the cytoplasmic but not nuclear fraction of normal human peripheral blood mononuclear cells, in normal human platelets, in T lymphocytes, non-T lymphocytes, and monocytes. The protein is produced in the B cell immunoblastic cell line DS-1, in normal EBV-transformed B cell lines, and in HEL92.1.7, but is barely detectable in MOLT-4 and not detectable in K562. WASP was present in two of four EBV-transformed cell lines from WAS patients. Splenic tissue immunostaining was performed in two patients, and the results correlated with the results of the Western blots. Sequence analysis of WASP cDNA from two patients who produce WASP show mutations causing amino acid substitutions. These studies establish a foundation for further studies aimed at understanding the function of WASP.     

Erythropoietin production in rats with post-ischemic acute renal failure

To study the role of erythropoietin (Epo) in the pathogenesis of anemia in acute renal failure (ARF), organ Epo mRNA was measured by RNase protection assay in rats with ARF induced by a one hour-occlusion of the left renal artery. Hematocrit was significantly decreased two hours, 24 hours and one week after renal artery occlusion. A significant reduction in serum haptoglobin at two hours and an increase in serum LDH at 24 hours indicated that hemolysis was the likely cause of the initial fall in hematocrit. However, despite the reduced hematocrit, serum Epo concentrations were not significantly different from controls, suggesting that the anemia is maintained because of lack of an appropriate Epo response. Right renal Epo mRNA levels were not significantly different in all groups, but Epo mRNA levels in post-ischemic kidneys were 50 to 67% lower than in contralateral kidneys. However, Epo mRNA in the post-ischemic kidney was increased sixfold by acute hemorrhage, a rise comparable to the ninefold increase observed in contralateral kidneys. In ARF rats exposed to 7.5% O2 for four hours, right kidney Epo mRNA increased 200-fold over normoxic levels, to a value similar to sham-operated hypoxic controls. Epo mRNA in the post-ischemic kidney also increased 200-fold, to 50% of the level in the contralateral kidney. Hepatic Epo mRNA levels were elevated to comparable levels in both groups. In this ARF model, mild anemia is associated with relative Epo deficiency. In the post-ischemic kidney, a substantial capacity for Epo production is retained but the sensitivity of the Epo response to blood oxygen availability is significantly reduced.     

Adhesives and nonshrinking dental resins of the future

Much attention has been directed toward producing dentinal adhesives that withstand the forces involved during polymerization shrinkage of composite resins. Studies have shown that an effective dentin-adhesive bond depends on the wetting and penetration characteristics of the dentinal adhesive system and the reactivity of the treated dentinal surface. The structure of the collagen in the demineralized dentinal layer also seems to influence the behavior of the bond. Adhesive systems that do not completely denature the fibrous collagen and leave interwoven banded collagen in the demineralized layer produce superior bond strengths (greater than 20 MPa). Other research efforts seek to develop a nonshrinking high-performance polymer for use as a matrix material for dental composite resins. Spiroorthocarbonates that expand during polymerization have been developed. In combination with a three-component epoxy comonomer, matrix resins have been produced that expand during polymerization and whose mechanical properties, water sorption, solubility, and degree of polymerization are acceptable for dental use. Further developments of nonshrinking composite resins and improved dentinal adhesives will greatly increase the longevity of 21st-century composite resin restorations and should significantly ease clinical placement.     

Effects of prenatal exposure to PCBs on the neurological function of children: a neuropsychological and neurophysiological study

To determine the long-term neurotoxicity of prenatal exposure to polychlorinated biphenyls (PCBs), 54 children--27 'Yu-Cheng' ('oil disease') children and 27 controls--were administered a battery of tests, including the WISC-R, auditory event-related potentials (P300), pattern visual evoked potentials (P-VEPs) and somatosensory evoked potentials (SSEPs). Full-scale IQ scores on the WISC-R were lower for the Yu-Cheng group than for the control group. Mean P300 latencies were significantly longer, and P300 amplitude significantly more reduced, in the Yu-Cheng group than in the control group at Cz and Pz. There were no significant difference in peak latencies and amplitudes between the two groups for P-VEPs and SSEPs. These findings suggest that prenatal exposure to PCBs tends to affect high cortical function rather than the sensory pathway in the developing brain.