Biomedical subjects

H S Taper

Publications and source records attributed to H S Taper.

At least 37 records · Page 2Linked to original sources

PubMed1992

Comparative hepatotoxicity of cholic acid, deoxycholic acid and lithocholic acid in the rat: in vivo and in vitro studies.

Until now, the cytotoxicity of the bile acids was mostly seen as being inversely associated with their degree of lipophilicity. The present study aimed at comparing the hepatotoxicity of cholic acid (CA), deoxycholic acid (DCA) and lithocholic acid (LCA), which are respectively, tri-, di- and monohydroxylated bile acids. For in vivo studies, the bile acids have been given at the dose of 0.5% or 1% in the diet of male Wistar rats for 2 weeks. The histological analysis of the liver, and the measurement of serum parameters of cytotoxicity and cholestasis (aminotransferases activity, bilirubin and total bile acids concentration), indicate that, among the bile acids tested, DCA is the most hepatotoxic, at both doses, while CA is the least hepatotoxic and cholestatic compound. Moreover, DCA is the only bile acid which, when given at the dose of 0.5%, induces lipid peroxidation in the liver, as evidenced by the measurement of thiobarbituric reactive substances in liver homogenates. The analysis of bile acids in liver homogenates by gas liquid chromatography revealed that feeding the animals with DCA results in its hepatic accumulation. Feeding rats with LCA or CA only slightly modifies the proportion of tri-, di- and monohydroxylated bile acids in the liver, as compared to controls. An in vitro experiment aimed at studying the hepatocellular lysis induced in vitro by the three bile acids by measuring the release of lactate dehydrogenase in the incubation medium of surviving hepatocytes in suspension. At a concentration of 1 mM, only DCA induces a significant cellular lysis, while at this concentration the lytic effects of CA and LCA are progressive and time-dependent. From this study, we gather that the hepatotoxicity of bile acids does not necessarily depend on their degree of hydroxylation. Our results are in accordance with some studies in rat hepatocarcinogenesis, showing a predominant initiating and promoting effects of DCA, as compared to LCA.

Administration, Oral↗

PubMed1991

The modulation of rat liver carcinogenesis by perfluorooctanoic acid, a peroxisome proliferator.

Perfluorooctanoic acid (PFOA) is a peroxisome proliferator. The aim of this study was to test for its ability to act as a positive modulator of hepatocarcinogenesis, in the so-called biphasic (initiation by diethylnitrosamine 200 mg/kg ip followed by treatment with the suspected modulators) and triphasic (initiation by the same dose of diethylnitrosamine followed by a selection procedure for 2 weeks consisting of giving 2-acetylaminofluorene and in the middle of this treatment a single dose of CCl4 followed by treatment with the suspected modulators) protocols of liver carcinogenesis. In both protocols treatment with PFOA increased the incidence of malignant hepatocellular carcinoma (HCC). As compared to phenobarbital, the modulating effect of PFOA is more pronounced in a biphasic than in the triphasic protocol. In parallel with positive modulation of HCC, PFOA also selectively induced the peroxisomal acyl-CoA oxidase activity and, to a lesser extent, catalase activity.

Acyl-CoA Oxidase↗

PubMed1990

Predictive value of serum alkaline DNase activity variations in treatment of head and neck cancer.

The aim of this study was to evaluate the variation in serum alkaline DNase activity (SADA) as a means of therapeutic monitoring in patients with head and neck cancer. Blood samples from 40 patients were collected before, during, and some weeks up to months after therapy. A decrease in SADA during treatment was usually associated with a primary clinical response, while no decrease indicated non-response to therapy. In patients with complete tumor regression the initial decrease of SADA was usually followed by an increase exceeding the initial level. A similar increase was not observed in patients with tumor progression.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1989

Serum alkaline DNase activity in normal or nonhospitalised individuals.

According to previous observations, the variations in serum alkaline DNase activity (SADA) appeared to be useful in monitoring malignant disease. In this study, SADA was measured in 625 individuals to explore nontumor-related factors which may influence SADA levels. The overall range in SADA was 0.2-82.3 kU/l. Women aged 50-79 years had higher (p less than 0.001) levels of SADA than younger females. A similar but less consistent effect of age was noticed in men (0.01 less than p less than 0.05). Older men had lower (0.01 less than p less than 0.05) SADA levels than the older women. Old women substituted with estrogens had lower (0.01 less than p less than 0.05) levels of SADA than those not treated with estrogens. SADA levels in pregnancy as well as postparturition were lower (p less than 0.001) than SADA values in nonpregnant females of similar age. In fertile women, no SADA variation was observed during the menstrual cycle and there was no significant effect of contraceptive pills. In males, SADA seemed unrelated to testosterone or cortisol levels but varied during the day. Smoking, alcohol consumption and drug therapy appeared to be without effect on SADA.

Adult↗

PubMed1989

Variations in serum alkaline DNase activity in rats during growth and treatment of tumors sensitive or resistant to therapy.

Serum alkaline DNase activity (SADA) was investigated in rats receiving s.c. transplants of tumor cells sensitive or resistant to chemotherapy. Serum samples from each animal were collected before transplantation, during the development of tumors and after therapy. Within a few days after transplantation of both tumor lines (sensitive or resistant), SADA levels decreased progressively to 52% of the normal pre-transplantation level (p less than 0.01). This decrease in SADA preceded by 4 to 5 days the appearance of any palpable tumor mass. In all untreated animals as well as in treated rats bearing resistant tumors, SADA remained at a low level until death. In rats bearing tumors sensitive to therapy a progressive increase in SADA was observed after treatment, paralleling tumor regression. When tumor regression was complete, SADA resumed the levels of activity measured prior to transplantation.

Adenocarcinoma↗

PubMed1989

Effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) treatment on human tumor cell growth in vitro. I. Synergism of combined vitamin C and K3 action.

The effects of sodium ascorbate (vitamin C) and 2-methyl-1,4-naphthoquinone (vitamin K3) administered separately or in combination on the in vitro cultured human neoplastic cell lines MCF-7 (breast carcinoma), KB (oral epidermoid carcinoma), and AN3-CA (endometrial adenocarcinoma) have been examined. When given separately, vitamin C or K3 had a growth inhibiting action only at high concentrations (5.10(3) mumol/1 and 10(5) nmol/l, respectively). Combined administration of both vitamins demonstrated a synergistic inhibition of cell growth at 10 to 50 times lower concentrations. At this level separately given vitamins are not toxic. The sensitivity to this treatment was somewhat different in the three cell lines, being slightly higher for KB line. This tumor cell growth inhibitory effect was completely suppressed by the addition of catalase to the culture medium containing vitamins C and K3, suggesting an excessive production of hydrogen peroxide as being implied in mechanisms responsible for the above-mentioned effects.

Adenocarcinoma↗

PubMed1989

Histochemical and biochemical studies on the effect of the prostacyclin derivative iloprost on CCl4-induced lipid peroxidation in rat liver and its significance for hepatoprotection.

In the present study, it was investigated whether the prostacyclin derivative Iloprost would protect hepatocytes against CCl4-induced liver injury and which mechanism(s) of hepatocellular pathogenesis might be affected by it. Rats were treated with a single oral dose of CCl4 (2 ml per kg); Iloprost was infused continuously from 2 to 4 hr before intoxication until killing. The following results were obtained. The CCl4-induced release of AST, lactate dehydrogenase and alkaline phosphatase into the serum was reduced by 50 to 70% in rats treated with doses of 0.1 and 0.5 micrograms Iloprost per kg per min. Infusion of 0.02 and 0.004 micrograms Iloprost per kg per min did not affect the CCl4-induced enzyme release into the blood. CCl4 induced the occurrence of aldehydes (products of lipid peroxidation), which were detected by histochemical and biochemical means. At 12, 48 and 72 hr after CCl4, the aldehyde-positive liver section area was about 58, 69 and 16% in rats treated with CCl4 alone, but only about 18, 13 and less than 1% in rats treated additionally with Iloprost. The aldehyde-positive hepatocytes were located predominantly in the centrilobular zone of the liver. At 24 hr the extent of the aldehyde-positive section area was the same in rats with or without Iloprost treatment (about 90%). Biochemical determination, however, revealed that at this time point the malondialdehyde content after Iloprost in rats was about 70% lower than without Iloprost treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗

PubMed1988

Variations in serum alkaline DNase activity. A new means for therapeutic monitoring of malignant lymphomas.

Our previously published clinical results suggest that the variations in serum alkaline DNase activity (SADA) could be a reliable marker for the therapeutic monitoring of different human malignancies. The aim of the study documented in this was to determine SADA variations in 27 patients suffering from malignant lymphomas (Hodgkin's and non-Hodgkin's). Patients continued to be observed after therapy. The blood samples were collected before treatment (Time 0), during several days from the onset of each treatment (Phase I), and weeks after the last therapy (Phase II). A decrease in the serum alkaline DNase activity during the first treatment indicates a good clinical response; no decrease indicates a nonresponse to treatment (Phase I). The Phase II data can be used to predict the long-term evolution of the disease. In patients who respond to therapy three types of variations of SADA are observed during this phase. A progressive regain of SADA up to a value exceeding the level of initial value (T0) correlates with a complete remission. An incomplete regain of activity corresponds to a partial remission. No regain of SADA precedes death.

Adolescent↗

PubMed1988

Histochemical detection of the in vivo produced cellular aldehydes by means of direct Schiff's reaction in CCl4 intoxicated rat liver.

A histochemical technique for detection of the in vivo induced cellular aldehydes based on the direct Schiff's reaction is reported in this paper. CCl4-intoxicated rat liver was used as an experimental model. Fresh and non-pretreated rat liver cryostat sections fixed in 10% formol calcium solution and washed in distilled water were exposed to Schiff's reagent. The sections were then immersed in two baths of sodium bisulphite solution, then in water, dehydrated in ethanol, cleared in xylene and mounted in a synthetic anhydrous mounting medium. As Schiff positive areas presented well circumscribed foci which increased with time following intoxication, semi-quantitative planimetric measurements were feasible. The direct Schiff's reaction detects cellular aldehydes in a sensitive, rapid, histologically and topographically estimable way. The appearance of these aldehydes precedes distinctly morphological alterations detectable by other histochemical or histological techniques. No positive results were obtained in control, non-intoxicated rat livers. Inhibition of this direct Schiff's reaction was obtained in positive control rat liver sections preincubated in solutions of aldehyde blockers. Histochemical detection of aldehydes may give useful information on different aspects of tissue and organ intoxication such as their topography, appearance, evolution, extension, consequences and effects of treatment. The direct Schiff's reaction can be considered as a valuable tool in fundamental and applied research dealing with various toxicological, environmental, pathological, cancer-related and therapeutic problems.

Aldehydes↗

PubMed1988

Characteristic variations of serum alkaline DNase activity in relation to response to therapy and tumor prognosis in human lung cancer.

The objective of the present study was to evaluate serum alkaline DNase activity (SADA) variations as a useful means of lung cancer monitoring therapy. SADA was measured in 40 patients with non-small cell and small cell carcinomas. Blood samples were collected before (Time 0), during the treatment and months after therapy. A decrease in SADA during the first treatment indicates a good clinical response, whereas an absence of decrease indicates a non-response to treatment. In patients who respond to therapy, three types of variations of SADA are observed during the clinical course. A progressive regaining of SADA up to a value largely exceeding the level of the initial SADA value (T0) correlates with a complete remission. An incomplete regaining of enzyme activity corresponds to a partial remission, whereas no regaining of SADA precedes a fatal evolution. Such variations in SADA observed in the 40 patients with lung carcinomas support our previously published clinical results, confirming that the variations of SADA could be a reliable marker for the therapeutic monitoring of different human malignancies.

Aged↗

PubMed1988

Analysis of antioxidant defense systems during rat hepatocarcinogenesis.

To better understand the role of free radicals in liver carcinogenesis, endogenous antioxidant defense systems and the susceptibility of membranes to lipid peroxidation were evaluated in early lesions and in malignant tumors induced by the Solt-Farber resistant hepatocyte protocol. These parameters were also measured in the liver surrounding these tumors. In comparison with the normal liver, both nodules and carcinomas show a different biochemical pattern consisting of decreased glutathione peroxidase (GSH peroxidase) and catalase activities plus increased glutathione reductase (GSSG reductase) activity. In contrast, 1 week after the application of the initiation-selection protocol, the liver displays a high level of glutathione (GSH), high GSSG reductase activity, a reduced production of malondialdehyde and no changes in superoxide dismutase and GSH peroxidase activities. These data suggest that the liver is well protected against reactive oxygen species. During the carcinogenic process, the liver parenchyma surrounding the altered foci recovers from most of the modifications induced by the initiation-selection treatment. These results add additional support for the hypothesis that the appearance of early alterations in the liver, after a carcinogenic treatment, might be an adaptive response to a hazardous environment in which selected cell populations are transformed into nodules and/or carcinomas.

Animals↗

PubMed1987

Non-toxic potentiation of cancer chemotherapy by combined C and K3 vitamin pre-treatment.

The influence on the survival of ascitic liver tumor (TLT)-bearing mice of combined vitamins C and K3 administered before or after a single i.p. dose of 6 different cytotoxic drugs, all commonly used in human cancer therapy, was investigated. Combined i.p. administration of these vitamins produced a distinct chemotherapy-potentiating effect for all drugs examined, especially when injected before chemotherapy. This potentiating treatment did not increase the general and organ toxicity that accompanies cancer chemotherapy. The possible generation of peroxides followed by membrane lipid alteration, DNase activation and DNA destruction by combined vitamin C and K3 in catalase-deficient cancer cells might be involved in the mechanisms of this selective potentiation.

Animals↗

PubMed1987

Dietary modulation of rat liver carcinogenesis.

Rat liver carcinogenesis was induced according to the resistant hepatocyte model of Solt and Farber. One week after the end of the procedure for the rapid growth of altered hepatocytes, one group of rats was submitted to a high fat (20%) regimen up to the end of the experiment. The incidence of histologically confirmed malignant hepatocarcinomas was compared with that observed in a group that remained on a normal diet. The modulating (promoting) effect of the high fat regimen was evident since nine out of 10 animals in this group bore macroscopically detectable tumors and eight out of 10 presented histologically confirmed hepatocellular carcinomas as early as 24 weeks after the beginning of the experiment. At that time, no malignant tumors were detected in the group submitted to the normal fat regimen. These results are similar to those resulting from a porto-caval shunt or the chronic administration of liver tumor promoters. This suggests that at this stage of the carcinogenic process, any treatment inducing chronically metabolic adaptation in a tissue containing preneoplastic nodules modulates positively the progression of these lesions as demonstrated by the dramatic reduction of the lag period for their malignant transformation.

Animals↗

PubMed1985

Quantitative histological and histochemical studies on the occurrence and stages of controlled cell death (apoptosis) during regression of rat liver hyperplasia.

Hyperplasia of the rat liver can be induced by cyproterone acetate (CPA). The fate of this hyperplasia after cessation of CPA treatment has been studied and the following findings were obtained: Liver DNA content decreased by about 25% within a few days after CPA withdrawal. In histological sections some hepatocytes showed degenerative changes. Among these, small membrane bounded bodies ("apoptotic bodies"; ABs) with or without chromatin were most numerous. Their incidence coincided with the phase of DNA elimination. Inflammatory reactions were not observed. Their small size and occurrence in clusters suggests that many of these ABs are formed by fragmentation of dying hepatocytes. Liver DNA was prelabelled with 3H-thymidine. Autoradiographic evaluation showed that many hepatocytes contained labelled nuclei, but unlabelled ABs. This finding strongly suggests that ABs, after the fragmentation stage, can be phagocytized by intact hepatocytes. About 80% of all ABs were found within hepatocytes. Extracellular ABs (early stage) contained no or very few active lysosomes. Intracellular ABs were sometimes surrounded by lysosomes, while others were in various stages of digestion. These observations suggest that the lysosomes of the phagocytizing hepatocytes degrade intracellular ABs, whereas intraapoptotic lysosomes seem to be inactive until the late stages of this degradation. Hepatocytes that did not replicate during CPA-induced liver growth appear to die off preferentially after CPA withdrawal. Retreatment with CPA greatly reduced the number of ABs within 4 h. Phenobarbital, another stimulus of liver growth, had the same effect. These findings suggest that the present type of cell death can be inhibited by growth stimuli and is therefore a controlled event serving to eliminate an excess of cells, rather than a manifestation of toxic injury to hepatocytes. The findings also suggest that this type of cell death and elimination is a rapid process completed within a few hours. It is concluded that cell death under the present experimental conditions probably occurs through apoptosis.

Animals↗

PubMed1983

Phenobarbital as a promoter in the initiation/selection process of experimental rat hepatocarcinogenesis.

Supplementary introduction of a phenobarbital (PB) promotion step after the Solt and Farber procedure dramatically increases the number of phenotypically-altered hepatocytes. These hepatocytes occupy approximately 40% of the liver volume after one week of PB treatment. These areas constitute a relatively uniform cellular population with altered histological phenotype and with distinct histochemical markers used by other authors for the detection of premalignancy. This procedure leads to the appearance of numerous hepatocellular carcinomas at approximately the 36 weeks stage. It was suggested that the early hepatocellular alterations after the initiation/selection procedure followed by PB might correspond to the hyperplasia of phenotypically-altered epidermal cells at the conversion step of mouse skin tumor promotion.

2-Acetylaminofluorene↗

PubMed1983

Morphological alterations and DNase deficiency in phenobarbital promotion of N-nitrosomorpholine initiated rat hepatocarcinogenesis.

Tumorigenic effect in rat liver was increased when phenobarbital was given chronically after N-nitrosomorpholine. In these rats the liver parenchyma surrounding pre- and neo-plastic lesions demonstrated distinct, mainly centrilobular zones of hypertrophic hepatocytes with abundant eosinophilic, filamentous cytoplasm, increase in nucleic acids and decrease in DNase activity. These alterations might be considered as signs of tumor-promoting activity of phenobarbital.

Animals↗

PubMed1981

Increase in nuclease activity as a possible means for detecting tumor cell sensitivity to anticancer agents.

Histochemical activity of nucleases was investigated in sensitive and resistant rat tumors at several periods after a single dose of cyclophosphamide and was compared with that in a control group of untreated tumors. Intense increase of nuclease activity(mainly that of acid DNAse) appeared only in the cells of the sensitive tumors at 12 hours, reaching its maximum three days after drug administration. Untreated malignant tumors usually have variable amounts of spontaneous necrosis with high nuclease activity. Not the absolute values of high nuclease activity but only the increase of such activity from the basal level of untreated tumors to that measured at frequent periods after trial treatment may be suggested as an early marker of therapeutically induced tumor cell necrosis. However, more investigation is needed before such a marker might be applied as a test for tumor sensitivity to therapeutic agents.

Animals↗

PubMed1981

Reversibility of acid and alkaline deoxyribonuclease deficiency in malignant tumor cells.

The nature of DNAse deficiency, which appears to be characteristic for malignant tumor cells, was investigated by the histochemical lead nitrate technique under various experimental conditions. Reappearance of distinct alkaline and acid DNAse activity was observed on the periphery of spontaneously occurring tumor necrosis, at early stages of the in vitro induced tumor necrosis, in necrotic tumor cells after in vivo irradiation and after in vitro treatment with different compounds. A membrane releaser did not reactivate DNAses in viable tumor cells, whereas the homogenate from tumor tissue inhibited DNAses in normal rat liver. These findings indicate that alkaline and acid DNAse deficiency in malignant tumor cells is a reversible phenomenon. This reversal of enzymatic activity has different histochemical and chronological patterns and specific reactivating factors for each DNAse. The masking effect of DNAse activity in malignant tumor cells is probably linked to natural enzyme inhibitors and its reversal to early stages of tumor necrosis.

Animals↗