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R Bose

Publications and source records attributed to R Bose.

At least 73 records · Page 4Linked to original sources
PubMed1990

Domoic acid-induced neurovisceral toxic syndrome: characterization of an animal model and putative antidotes.

A rodent model of neurovisceral toxic syndrome induced by the neuroexcitant amino acid, domoic acid, is described, along with the activity of a putative antidote, the nonselective excitotoxin antagonist, kynurenic acid. Both an extract of contaminated mussels and pure domoic acid induced a characteristic syndrome including: sluggishness, scratching stereotypy, convulsions and death. Autopsy revealed gastric and duodenal lesions and peritoneal ascites. Kynurenic acid significantly obtunded these behavioral and physiological effects, particularly when given 60-75 min after the toxic insult. Probenecid, a blocker of organic acid transport, and tryptophan, a precursor of endogenous brain kynurenic acid, increased the time frame in which kynurenic acid exerted its protective effects. Kynurenic acid alone, in nontoxin-challenged animals significantly blocked cold-stress gastric lesions, significantly reduced basal gastric acid secretion and was protective to a lesser degree against ethanol-induced gastric mucosal injury. The murine model of domoate toxicity represents an inexpensive, reliable and sensitive biological assay for screening commercial shellfish for excitotoxin contamination. We are currently exploring kynurenic acid and other compounds for possible therapeutic use in both current and any future victims of neuroexcitant amino acid toxicosis.

Animals↗
PubMed1990

Gastrointestinal effects of contaminated mussels and putative antidotes thereof.

A recent outbreak of amnesic shellfish poisoning (ASP) in Atlantic Canada was characterized by severe gastrointestinal and central nervous system pathology. We examined the gastrointestinal effects of an acidic extract of blue mussels contaminated with domoic acid, the suspected toxin responsible for the ASP. We also tested the gastric effects pure domoic acid as well as a putative antagonist of neuroexcitant amino acid receptors, kynurenic acid. Mussel extract produced gastric (antral) ulcers, duodenal ulcers, gastric and duodenal hyperemia and bleeding, as well as peritoneal ascites. Kynurenic acid protected significantly against extract-induced gastropathy, particularly when given 60 or 75 minutes after extract. Pure domoic acid resulted in fatalities in all infant mice tested. These animals exhibited gastric bleeding and hemorrhage, especially at the higher doses employed. In otherwise untreated rats, kynurenic acid exerted significant anti-stress ulcer and anti-gastric secretory effects, but was less effective at blocking ethanol-induced gastric lesions. We suggest that there may be both peripheral as well as central effects of kynurenic acid in modulating normal and pathological gastric function.

Animals↗
PubMed1990

Sensitive murine model and putative antidotes for behaviorial toxicosis from contaminated mussel extracts.

The recent outbreak of "amnesic" mussel poisoning syndrome, attributed to domoic acid contamination of edible mussels claimed several lives and left many victims impaired with a peculiar loss of memory. We administered the whole mussel extract (WMX) and the mussel hepatopancreas extract (MHX, hepatopancreas being the major site for sequestration of domoic acid in mussels) in Swiss-Webster mice. A characteristic syndrome featuring sluggishness, scratching stereotypy, convulsions and death was noticed. Infant mice were some 3- to 4-fold more sensitive to the WMX toxicity. Kynurenic acid (KYN), an endogenous nonselective excitotoxin antagonist offered significant protection against the toxicosis after its onset had been provoked by the mussel extract. This observation emphasizes the feasibility of using KYN or related compounds in the therapy of poisoning from excitotoxins. As a logical extension of this possibility we examined the possibility that endogenous KYN could be exploited for similar protection against domoate toxicosis in our murine model. The time frame during which KYN was protective was increased by probenecid, a blocker of organic acid transport and by tryptophan, a precursor of endogenous KYN. We examined also the classical anticonvulsants phenytoin and ethosuximide, as well as dextromethorphan at its excitotoxin antagonistic dose. The infant mouse model of domoate-toxicity holds promise for being developed into a rapid, sensitive, reliable and inexpensive biological assay for screening commercial batches of mussel for excitotoxin contamination. Kynurenic acid and dextromethorphan should be further examined as antidotes for possible therapeutic use in existing victims and in the treatment of future domoate toxicosis occurring here or elsewhere.

Age Factors↗
PubMed1990

Antiulcer activity of N-phthaloyl GABA--a new GABA mimetic agent.

N-phthaloyl GABA (P. GABA) inhibited gastric ulceration induced by 3 hr restraint stress at 4 degrees C (CRS) in albino rats. Antiulcer activity of P. GABA was compared with sodium valproate and cimetidine. P. GABA, sodium valproate and cimetidine showed a dose dependent reduction of gastric ulceration. Pretreatment with GABA antagonists-bicuculline methiodide (0.5 mg/kg, im) or 3 mercaptopropionic acid (2 mg/kg, im) reversed the antiulcerogenic activity of both the drugs (P. GABA and sodium valproate). GABA antagonists as such did not induce gastric ulceration in normal rats.

3-Mercaptopropionic Acid↗
PubMed1989

Biological and methodological implications of prostaglandin involvement in mouse brain lipid peroxidation measurements.

Enhanced cyclooxygenase-mediated prostaglandin (PG) turnover occurring during sacrifice and biochemical processing of tissues also generates malondialdehyde (MDA), a product of lipid peroxidation (LPO). Studies reporting on LPO estimated by thiobarbituric acid reactive substances (TBARS) have failed to consider such artefactual increases. This study reports the relative proportion of PG metabolism-derived MDA (PG-MDA) in mouse brain regions during the TBARS assay. The cyclooxygenase inhibitor indomethacin significantly lowered MDA in fronto-parietal cortex and corpus striatum. Indomethacin (50-800 micrograms/ml, in vitro) increased estimated TBARS in whole brain. Such enhancement was absent when indomethacin (20-80 micrograms/sample) was added to the MDA standard curve, reflecting its interaction with TBARS other than MDA. PG-MDA contributes as much as 15% to the total estimated value of MDA in fronto-parietal cortex and corpus striatum and must be corrected for in LPO studies.

Animals↗
PubMed1989

Purified human early pregnancy factor from preimplantation embryo possesses immunosuppresive properties.

This study was undertaken to determine whether early pregnancy factor secreted by preimplantation embryos has immunosuppressive properties. Human early pregnancy factor was purified from embryo growth media of in vitro fertilized ova with ion-exchange and gel filtration chromatography. During each step of purification the fractions were tested for (1) early pregnancy factor activity with the rosette inhibition assay, (2) immunosuppressive properties with a concanavalin A-stimulated lymphocyte proliferation assay, and (3) purity by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Results indicate that (1) human early pregnancy factor has a basic molecular weight of 14 kd, (2) early pregnancy factor has immunosuppressive activity, (3) polymers of early pregnancy factor also appear to be present in the embryo growth media, and (4) immunosuppressive factors other than early pregnancy factor are also secreted by preimplantation human embryos. Early pregnancy factor and other factor(s) produced by the preimplantation embryo may play a role in suppressing maternal cellular immune responses, thereby preventing maternal rejection of the embryo.

Blastocyst↗
PubMed1989

Human embryo associated immunosuppressor factor(s) from pre- and post-implantation stages share some similarities.

The present study demonstrates that embryo associated immunosuppressive factor(s) (EASF) secreted by the human embryo at pre- and post-implantation stages share some similarities. Human EASF was partially purified from embryo growth media of in vitro fertilized ova and from first trimester pregnancy sera. Non-pregnancy sera were fractionated in parallel. During each step of purification the fractions were tested for immunosuppressive properties using concanavalin A-stimulated lymphocyte proliferation assay. Analysis of EASF positive fractions on SDS-PAGE identified 14 kDa and 24 kDa molecules in embryo growth media and pregnancy sera. No such molecules were found in control sera, suggesting that these factors are embryo associated. The relationship of pre- and post-implantation EASF was also analyzed by EASF binding assay using murine anti-EASF antibody, which was raised against EASF isolated from embryo growth media. Results show that murine antibody bound to EASF purified from pregnancy sera, but not to identical fractions from control sera, indicating that these post-implantation EASF possess some similarity with pre-implantation EASF. Results also indicate that a species of suppressor factors present in embryo growth media and pregnancy sera were unique for their origin. Presence of these three EASFs at various stages of gestation may play a role in suppressing maternal cellular immune responses thereby preventing maternal rejection of the embryo.

Blastocyst↗
PubMed1989

Neurotoxicity and lethality of toxic extracts from Atlantic coast shellfish.

1. HCl-extract of poisonous shellfish was injected i.p. into Swiss-Webster mice. 2. Behavioral effects (sluggishness, scratching, huddling, clonic convulsions, respiratory distress and mortality) were noted. 3. Infant mice were more sensitive than were the adults to XTRT toxicity. Estimated LD50 values were; adult: 34.8 ml/kg i.p., infant: 9.6 ml/kg i.p. 4. The mouse model of shellfish-toxicity offers the advantages of a degree of similarity with the human clinical situation and a rapid time course for screening antagonists against shellfish poisoning.

Aging↗
PubMed1989

Kynurenic acid protects against gastroduodenal ulceration in mice injected with extracts from poisonous Atlantic shellfish.

1. Mice were treated with an extract prepared from poisonous Atlantic mussels. 2. Gastric and duodenal ulcers, duodenal hyperemia and peritoneal ascites resulted from administration of the shellfish extract, with an LD84 of 1.0 ml. 3. Kynurenic acid, an antagonist at excitatory amino acid receptors, protected significantly against gastroduodenal ulcers, ascites and hyperemia when given at 60 or 75 min post-extract. 4. It is likely that the gastrointestinal damage evoked by this extract is due to its domoic acid content and that kynurenic acid may prove useful against domoic acid-induced gastropathy.

Animals↗
PubMed1989

Kynurenic acid protects against neurotoxicity and lethality of toxic extracts from contaminated Atlantic coast mussels.

1. An aqueous acidic extract from poisonous Atlantic coast mussels was injected i.p. into groups of Swiss-Webster mice at the LD84 value (= 40 ml of extract/kg). Body-scratching, clonic convulsions and death were consistently observed in response to XTRT injection. These results are consistent with the presumed presence of the neuroexcitant amino acid, domoic acid, in the contaminated mussels. 2. Kynurenic acid at 300 and 600 mg/kg i.p. protected powerfully and significantly against extract-induced neurotoxicity. Greatest protection was observed when the antidote was administered between 30 and 90 min after injection of the toxic extract.

Animals↗
PubMed1988

Effects of 4-acetylpyridine on stress ulcer formation in mice.

4-Acetylpyridine, earlier reported by us to be an anticonvulsant, offers long-lasting protection after a single administration against hypothermic restraint stress-induced gastric ulceration in mice. Electroshock convulsions, marginally but not significantly protective against such ulcers themselves, when coupled with 4-acetylpyridine administration fully prevented gastric ulcers from occurring in this murine model of experimentally induced stress.

Animals↗
PubMed1988

Membrane transport changes in an adriamycin-resistant murine leukemia cell line and in its sensitive parental cell line.

Multidrug resistance in cancer chemotherapy occurs when cells develop resistance towards structurally and functionally unrelated drugs. It is speculated that alteration of some fundamental process(es) in the cells leads to the development of multidrug resistance. The sodium pump activity of murine leukemia cell lines P388/S (sensitive) and P388/ADR (resistant) was measured and found to be different in the two cell lines. The rate of sodium pumping, i.e., the ouabain-sensitive rubidium uptake, was consistently lower in the resistant cells compared to their parental controls. Uptake of adriamycin was lower in the resistant cells. Depolarizing the cells with potassium chloride or by inhibiting the pump with ouabain increased the adriamycin uptake in the sensitive cells but not in the resistant cells. Adriamycin did not have any acute effects on the sodium pump activity. It is concluded that the development of drug resistance in cell line P388 is associated with a decrease in sodium pump activity and a lack of depolarization-induced adriamycin uptake; these processes may be causally linked via alterations in cytosolic calcium concentration.

Animals↗