Cutaneous toxicity of sodium lauryl sulphate, nickel, and their combination in guinea pigs: biochemical and histopathological observations.
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Biomedical subjects
Publications and source records attributed to R Shanker.
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Three infection models namely an oncogenic virus Encephalomyocarditis (EMCV), a rodent strain of malaria, Plasmodium berghei, and a rodent hookworm parasite, Nippostrongylus brasiliensis, were used to confirm the in vivo immunotoxic potential of styrene reported in our previous communication. The altered host resistance to these challenge infections was evaluated in rodents pre-treated with 0, 0.02, 0.03 or 0.05 x LD50 dose of styrene (5 days/week) for 4 weeks. Significantly increased mortality in mice was observed at the various tested dose levels of styrene when challenged with EMCV. Similarly the results obtained in the malaria infection model indicated increased blood parasitaemia as well as significantly enhanced mortality in styrene-treated animals. Also the rejection of N. brasiliensis was also found to be significantly impaired in animals treated with a higher dose of styrene. These results indicate that the exposure of rodents to styrene can markedly impair host resistance which may have biological significance.
Mice were fed for 24 weeks with three different subtoxic dosages of gamma-HCH (0.012, 0.12 and 1.2 mg/kg) mixed in powdered feed. The immunological profile was assessed at an interval of one month during the entire exposure period. Both the cell mediated and humoral components of immunity showed a biphasic response characterized initially by stimulation followed by suppression in a dose dependent manner. However, gamma-HCH did not affect the functional properties of peritoneal macrophages. Histological changes in lymphoid organs were in accordance with the biphasic immunomodulatory effects of gamma-HCH.
The effect of a single dose of intermediate acting (Lente) insulin given subcutaneously at 9.00 P.M. in 22 NIDDM subjects refractory to a combination of Sulphonylureas and Biguanides was analysed. Euglycemia was achieved and maintained during the study period of three months with a mean insulin requirement of 14.22 +/- 5.98 units/day. Plasma FFA, Total cholesterol, triglyceride and VLDL-cholesterol also showed significant reduction. The level of FFA modulates hepatic glucose production, which in turn correlates positively with the fasting blood glucose. The therapeutic modality of bed time Lente Insulin based on physiological principles is an effective way of achieving glycemic control in NIDDM subjects who have become non-responsive to oral hypoglycemic agents.
Pathomorphological and immunological studies were carried out on rodents following oral administration of 0, 0.1, 0.25 and 0.5% (w/w) metanil yellow, mixed in diet, for 30 days. No significant change in hematologic parameters and histologic architecture of liver, kidney, mesenteric lymph node, thymus and urinary bladder was observed except for mild desquamation of intestinal villi and moderate changes in Peyer's patches of small intestine with higher doses. Among immunological parameters, significant enhancement in the primary humoral immune response (anti-SRBC IgM plaque forming cells of spleen) was observed with the lowest dose of metanil yellow while higher doses produced opposing effects. An elevated cutaneous delayed type hypersensitivity (DTH) reaction to SRBC was seen in 0.1% metanil yellow treated animals but higher doses did not influence the reaction. The treatment also caused changes in functional capabilities of macrophages. Although these immune alterations could hardly influence the local immunity of gut, as measured by the capacity of animals to cause rejection of Nippostrongylus brasiliensis parasite, the potential to modulate the immunity in general by metanil yellow however assumes considerable biological significance.
Oral administration of trichloroethylene (TCE; 0, 500, 1000 and 2000 mg/kg/day) to male mice once daily, 5 days a week for a period of 28 days, caused a significant increase in liver weight, degeneration/necrosis of hepatocytes and characteristics proliferation of endothelial cells of hepatic sinusoids. Increase in kidney weight, glomerular nephrosis, degeneration/desquamation of tubular epithelium and characteristic amyloid deposition in glomeruli were observed only in the group of mice treated with 2000 mg/kg TCE. These changes occurred concurrently with a significant increase in total protein and free sulphydryl contents, elevated activities of acid phosphatase and catalase and decreased activity of delta-aminolevulinic acid dehydratase (delta-ALAD) indicating the sensitivity of liver and kidney as target tissues in TCE-toxicity. Hematological studies showed a significant increase in RBC counts and a reduction in WBC counts without any statistically significant change in the hemoglobin, urea nitrogen, creatinine and uric acid levels in the blood of TCE-exposed mice. A dose-related increase in cell density and acid phosphatase activity with a parallel significant decrease in the activity of delta-ALAD were observed in the bone marrow, which appear to be responsible for hematological alterations in TCE-exposed mice. The results suggest that early metabolic, pathological and hematological perturbations following a short-term exposure of TCE in mice, can provide the basis for its documented potential for chronic effects like blood dyscrasia and cancer.
The skins of guinea pigs were exposed to 50 mg/kg hexachlorophene (HCP) for 7, 15 or 30 days. The activities of skin marker enzymes (beta-glucuronidase, histidase, tyrosinase) increased, but glutathione decreased. Lipid peroxidation and histamine contents increased during different time intervals. The histopathological changes showed damage to epidermis and dermis. Depending on the duration of exposure, HCP produces biochemical and histopathological damage to skin.
PVC dust, following a single intratracheal instillation (25 mg/rat), was substantially cleared through the lymphatic circulation and progressively accumulated in the tracheobronchial lymph nodes (TBLN) in a time-dependent manner for up to 1 year. The tissue response in TBLN during 60-270 days post-instillation of PVC dust was characterized by progressive increase in total organ fresh weight, dry weight, DNA, RNA and protein contents, concurrent with the proliferation of macrophages and hyperplasia of reticular cells. Active phagocytosis and enhanced hydrolytic activity in TBLN was evident around 270 days post-instillation by the appearance of PVC-laden macrophages near and within the dust foci, and increased activity of acid phosphatase, DNAse, RNAse and beta-glucuronidase. PVC dust caused degeneration of macrophages, and consequent release of hydrolytic enzymes resulted in limited cytotoxicity without inducing reticulination and fibrosis in the TBLN. The histology and clinical biochemistry of liver, kidney, spleen and serum were not altered and there were no detectable PVC particles in these tissues at up to 365 days. It is therefore concluded that lymphatic clearance of intratracheally instilled PVC dust results in its accumulation and mild foreign body reaction in TBLN which is non-fibrogenic at up to 365 days post-instillation.
Fifty-five hepatobiliary scintigraphic studies using 99mTc-Mebrofenin were performed in 52 orthotopic liver transplant patients to evaluate suspected biliary complications, namely biliary extravasation and extrahepatic obstruction. Final diagnosis was made by analysis of the clinical course and other procedures. Three out of three studies of biliary leak and four out of five studies of biliary obstruction were detected. There were no false positives in either complication. The sensitivity, specificity and accuracy were 100, 100, 100% for ectravasation and 80, 100, 98% for obstruction, respectively. Hepatobiliary scintigraphy appears to be an accurate means of detecting biliary leak and obstruction associated with the transplanted liver.
The guinea pigs were dermally exposed to paraphenylene diamine (PPD) at a dose level of 0.1 ml day-1 of a 1.0% (w/v) solution of PPD for 1, 3, 5 and 7 days. The absorption of PPD and its effects on lipid peroxidation, glutathione, histamine and several enzymes were assessed in skin and serum. Histopathological changes in liver, kidney and skin were examined also. The findings of the study indicated that PPD exposure resulted in significantly increased levels of lipid peroxidation and histamine contents in skin. The activity of enzymes increased significantly in skin and serum. PPD exposure also showed degenerative changes in liver and hyperkeratosis together with infiltration of cells in the dermis. Biochemical defects and histopathological changes in skin and serum correlated with the duration of exposure.
Acrylamide, a neurotoxic monomer with extensive industrial applications was found to be degraded by the microorganisms present in a tropical garden soil. A bacterium capable of degrading acrylamide was isolated from this soil by enrichment. It was found to be aerobic, gram-negative, motile, short rod and identified as Pseudomonas sp. The bacterium degraded high concentrations of acrylamide (4 g/l) to acrylic acid and ammonia which were utilized as sole carbon and nitrogen source for growth. An amidase was involved in the hydrolysis of acrylamide, which could act on other short chain amides like formamide and acetamide but not on acrylamide analogues: methacrylamide and N,N-methylene bisacrylamide. The enzyme was sensitive to catabolite repression by succinate both in presence as well as absence of nitrogen source.
The distribution of chlorpromazine (CPZ) between aqueous buffer solutions and 1-octanol was studied over a wide range of pH, buffer concentration, and temperature. A mathematical model was developed to simulate the distribution profiles. It is assumed that only monomers of CPZ exist in the organic phase, whereas in the aqueous phase, association equilibria were assumed to occur. The model predicted the formation of dimers and no higher aggregates over most of the concentration range covered in this study. Thermodynamic parameters for the partition equilibria were evaluated from the equilibrium partition coefficients measured as a function of temperature. Positive values of delta H and delta S were obtained for the transfer of CPZ from the aqueous to the organic phase. The process is entropy controlled indicative of a hydrophobic interaction between CPZ and the aqueous solvent.
The role of histamine in modulating the immune response of hamsters infected with Ancylostoma ceylanicum (hookworm) was investigated. Histamine administration (20 mg base/hamster x 6 ip) made the immune hamsters susceptible to challenge infection, and on assay the humoral as well as the cell-mediated responses were found to be suppressed. An adverse effect of histamine was observed on lymphocytes but the macrophage function remained unaltered, since the latter lack histamine receptors. These findings provide definite evidence that histamine suppresses specific immune responses, and that contrary to earlier reports this neurotransmitter does not play a direct role in the 'self-cure' phenomenon.
The linear alkylbenzene sulphonate (LAS) based synthetic detergents-induced decrease in lipid peroxydation and increase in histamine content in exposed skin of guinea pigs in a dose-dependent manner. Histopathological alterations of exposed skin included moderate degree of hyperkeratinization at lower concentration but necrosis, scarring, sloughing as well as discontinuity of epidermis at higher concentrations. The results shows that the contact of skin with detergents causes dermal toxicity.
Pups (5 days old) were undernourished by separating them for 14 hr daily from their mothers for 7, 10, 13, 16 and 20 days. The undernourished rats showed significant decrease in body and brain weight, protein and nucleic acid contents at all stages of observation as compared to controls. The activities of SDH and AChE enzymes were decreased significantly after 10 days and onwards in undernourished rat brain. However, maximum decrease in brain protein, nucleic acid contents and enzyme activities was observed during suckling-weaning-transition (20-21 days). Such alterations in enzyme activities may be correlated with the reduced oxidative and neurotransmission function in undernourished developing rat brain.
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Male mice given different oral doses (0.05, 0.03 or 0.02 x LD50/animal/day) of styrene (LD50 = 1 g/kg) daily for 5 days did not incite any overt toxicity in lymphoid organs or on hematologic parameters. At the tested dose levels styrene produced a mild reduction in the organ weight of adrenal and spleen and slight reduction in the cellular viability of lymph nodes. There was a dose-dependent suppression in the humoral immune response (IgM-producing PFCs of spleen and serum anti-SRBC HA titre) to SRBC. The proliferative response to the B-cell mitogen, LPS however revealed a significant increase in the incorporation of 3HT with middle and lowest doses of styrene. The results of cell-mediated immunity appeared somewhat unexpected and more complex as exposure resulted in a dose-dependent enhancement in the cutaneous DTH reaction to SRBC together with increased blastogenic response of splenic lymphocytes to phytohaemagglutinin (PHA). Additionally, there was significant impairment in the functional activity (NBT reduction, attachment and phagocytic indices) of nonadherent and adherent peritoneal exudate cells. Based on the present data the study identifies the immunotoxic potential of styrene and which acts differently on various arms of the rodent's immune system.
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