Evaluation of endomorphin-1 on the activity of Na(+),K(+)-ATPase using in vitro and in vivo studies

The goal of this study was to investigate the effects of endomorphin-1 on Na(+),K(+)-ATPase activity in mouse brain synaptosome in vitro, and its antinociceptive interaction with the Na(+),K(+)-ATPase inhibitor ouabain. Endomorphin-1 (0.1 nM-10 microM) produced a concentration-dependent (EC(50): 43.19 nM, CI: 23.38-65.71 nM, E(max): 25.86%, CI: 24.53-27.20%), naloxone-reversible increase of the synaptosomal Na(+),K(+)-ATPase activity. The intrathecally (i.t.) administered endomorphin-1 (2-20 microg) produced a dose-dependent short-lasting increase in the tail-flick latency. Ouabain itself (1-1000 ng, i.t.) did not cause antinociception. Treatment with 10 ng ouabain significantly decreased the antinociceptive effect of 2 microg endomorphin-1, but none of the other combinations did significantly differ from the endomorhin-1-treated groups. These data indicate that endomorphin-1 increases the activity of Na(+),K(+)-ATPase in vitro but this effect may play a weak role in the antinociception induced by intrathecal endomorphin-1.     

Oxidative stress as a possible mode of action for arsenic carcinogenesis

Many modes of action for arsenic carcinogenesis have been proposed, but few theories have a substantial mass of supporting data. Three stronger theories of arsenic carcinogenesis are production of chromosomal abnormalities, promotion of carcinogenesis and oxidative stress. This article presents the oxidative stress theory along with some supporting experimental data. In the area of which arsenic species is causually active, recent data have suggested that trivalent methylated arsenic metabolites, particularly monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)), have a great deal of biological activity. Some evidence now indicates that these trivalent, methylated, and relatively less ionizable arsenic metabolites may be unusually capable of interacting with cellular targets such as proteins and even DNA. Thus for inorganic arsenic, oxidative methylation followed by reduction to trivalency may be a activation, rather than a detoxification pathway. This would be particularly true for arsenate. In forming toxic and carcinogenic arsenic species, reduction from the pentavalent state to the trivalent state may be as or more important than methylation of arsenic.     

Production and characterization of monoclonal antibodies with specificity for human HLA-G isoforms

Production of monoclonal antibodies to HLA-G, a nonpolymorphic antigen of non-classical HLA class I, is of basic and clinical importance. In the present study, monoclonal antibodies were prepared which recognize different membrane bound and soluble isoforms of HLA-G, following immunization of BALB/c mice with a synthetic peptide. Use of this peptide (23 residues), which is present in the alpha1 domain of HLA-G, was previously demonstrated to provide antibodies useful for recognition of HLA-G isoforms in human placenta. Antibody-producing hybridomas were screened by an indirect one-step ELISA method. A clone designated 5E6H7, secreted antibodies useful in immunostaining studies involving both surface HLA-G of placental tissues and soluble forms of this antigen in human sera. In addition, unreactivity of this antibody with human lymphocytes and sections of normal human skin was observed by immunofluorescence microscopy, thus demonstrating its specificity for HLA-G.     

Production and characterization of monoclonal antibodies to fowl adenoviruses

A panel of 10 monoclonal antibodies to a hypervirulent fowl adenovirus (FAdV) strain 398A was produced. Monoclonal antibodies (mAbs) were characterized for their isotype, neutralizing activity, ability to capture viral antigens, immunoblotting of viral polypeptides, competitive inhibition with chicken antisera and their reaction pattern with other FAdVs in indirect immunoperoxidase. Eight out of 10 mAbs reacted strongly in indirect immunoperoxidase staining with most of the FAdVs isolated from inclusion body hepatitis in Australia. One of these mAbs (6E1) was found to specifically react with the strains presumably characterized as hypervirulent FAdVs. IgG2a was the predominant sub-isotype. Two out of 10 mAbs neutralized the homologous strain of virus and six captured their target antigen onto a plastic surface. Chicken anti-serum to FAdV strain 398A inhibited the reaction of the seven mAbs that bound with high affinity in a blocking competitive enzyme-linked immunosorbent assay. This panel of mAbs can be used to improve diagnostic assays, study pathogenesis and carry out strain identification.     

Reversible acute renal failure associated with hypothyroidism: report of four cases with a brief review of literature

SUMMARY:   We present four adult cases of acute renal failure associated with hypothyroidism. All patients presented with symptoms suggestive of moderate to severe hypothyroidism, such as cold intolerance, constipation, muscle weakness, and lower extremity oedema. Initial serum creatinine levels ranged between 115 and 203 µmol/L (1.3 and 2.3 mg/dL), with creatinine clearances (CrCl) ranging between 0.58 and 0.97 mL/s (34.5 and 58 mL/min). After 6–12 weeks of treatment with levothyroxin, serum creatinine levels decreased to the range of 80 and 124 µmol/L (0.9 and 1.4 mg/dL) and CrCl increased to 0.74–1.64 mL/s (44–98 mL/min). One patient had proteinuria of 800 mg/day, which decreased to the normal range (<200 mg/day) after levothyroxin treatment. One patient developed acute gouty arthritis before normalization of thyroid-stimulating hormone (TSH), which was successfully managed with prednisone therapy. All of our patients had increased creatine kinase (CK), ranging between 1000 and 2360 U/L (normal range, 22–165 U/L), which normalized after 6 weeks of levothyroxin treatment.