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Biomedical subjects

A A Horton

Publications and source records attributed to A A Horton.

At least 19 recordsLinked to original sources
PubMed1991

Prevention of Ca(2+)-induced or thromboxane B2-induced hepatocyte plasma membrane bleb formation by thromboxane receptor antagonists.

Isolated hepatocytes incubated in the presence of either Ca2+ ionophore A23187 or thromboxane B2 develop many plasma membrane blebs which are a characteristic feature of toxic or ischaemic cell injury. When hepatocytes are incubated in the presence of both Ca2+ ionophore A23187 and any one of three thromboxane receptor antagonists (SK and F 88046, B.M. 13505, B.M. 13177), bleb formation is strongly inhibited. Hepatocytes incubated in the presence of both thromboxane B2 and any one of the three thromboxane receptor antagonists are also well protected from the formation of blebs. Treatment of isolated hepatocytes with Ca2+ ionophore A23187 is known to stimulate the production of thromboxanes. The data presented are consistent with thromboxane B2 acting as an intermediary in a proposed mechanism of cell injury and death in which elevated cytosolic free Ca2+ levels activate phospholipase A2 and the arachidonate cascade.

Animals↗
PubMed1990

Coping and stress in families of child psychiatric inpatients: parents of children with depressive and schizophrenia spectrum disorders.

Coping and disruption were examined in parents of children with depressive and schizophrenia spectrum disorders. Parents described disruption in their family lives, relationships, leisure time, and work functioning. High maternal disruption was associated with the absence of intimate relationships and child chronicity. Parents most frequently reported using active cognitive coping strategies, but with the advantage of hindsight, advised seeking community resources for helping their children.

Adaptation, Psychological↗
PubMed1990

Prevention of thromboxane B2-induced hepatocyte plasma membrane bleb formation by certain prostaglandins and a proteinase inhibitor.

Isolated hepatocytes incubated in the presence of thromboxane B2 developed many plasma membrane blebs which are a characteristic feature of toxic or ischaemic cell injury. When hepatocytes were incubated in the presence of both thromboxane B2 and the non-lysosomal proteinase inhibitor, leupeptin, were also well protected from the formation of blebs. This implies that thromboxane B2 is able to activate non-lysosomal proteinases which appear to attack certain cytoskeletal proteins. The data presented are consistent with thromboxane B2 acting as an intermediary in a proposed mechanism of cell injury and death in which elevated cytosolic free Ca2+ levels activate phospholipase A2 and the arachidonic acid cascade.

16,16-Dimethylprostaglandin E2↗
PubMed1989

Effects of inhibitors of phospholipase A2, cyclooxygenase and thromboxane synthetase on paracetamol hepatotoxicity in the rat.

This paper describes work on a proposed hypothesis of cell injury and death in which an hepatotoxin-induced rise in cytosolic free Ca2+ concentration activates phospholipase A2 (PLA2) resulting in the release of arachidonic acid (A.A.) from membrane phospholipids. A.A. is then converted to eicosanoids which are known to be formed during chemical cell injury. A rise in cytosolic free Ca2+ level (indicated by increased glycogen phosphorylase "a" activity) occurs about 12 h after paracetamol administration to rats. Inhibitors of PLA2, cyclooxygenase and thromboxane synthetase injected i.p. 7 h after paracetamol prevented hepatotoxicity as measured by SGPT activity but did not prevent an increase in glycogen phosphorylase "a" activity. Serum 11-deoxy-13,14-dihydro-15-keto-11 beta, 16 epsilon-cyclo prostaglandin E2 and thromboxane B2 measured by radioimmunoassay increased substantially soon after the increase in glycogen phosphorylase "a" activity. The data presented support the proposed sequence of events in which A.A., released from membrane phospholipids by Ca2(+)-activated PLA2, acts as substrate for the synthesis of cytodestructive eicosanoids.

Acetaminophen↗
PubMed1987

Histochemical and biochemical observations on the cytotoxicity of paracetamol and its effects on glycogen metabolism in rat liver.

The effects of paracetamol overdose on glycogen metabolism in rat liver have been investigated and related to its cytotoxicity. Paracetamol was administered to male rats by gavaging after a 24-h fast and refeeding was not permitted. An early (9-12-h) increase in histochemically demonstrable glycogen phosphorylase alpha activity in perivenous hepatocytes preceded major loss of membrane integrity as assessed by serum glutamate-pyruvate transaminase (SGPT) activity and uptake of trypan blue during perfusion. These changes occurred only after a decrease in the concentration of reduced glutathione, which is generally observed about 4 h after paracetamol treatment. The activation of glycogen phosphorylase in perivenous hepatocytes occurred concurrently with an increase in glycogen content of periportal hepatocytes, indicating a clear heterogeneity in the response of the two-cell populations to the hepatotoxin. The use of trypan blue perfusion together with histochemical techniques allowed changes in glycogen content and phosphorylase alpha activity of individual hepatocytes to be assessed with reference to the extent of membrane damage evident. The relevance of the results to possible mechanisms of hepatotoxicity is discussed.

Acetaminophen↗
PubMed1987

Lipid peroxidation and mechanisms of toxicity.

Aerobic organisms by definition require oxygen, and the importance of iron in aerobic respiration has long been recognized, but despite their beneficial roles, these elements can pose a real threat to the organism. During oxygen reduction, reactive species such as O2-. and H2O2 are formed readily. Iron can combine with these species, or with molecular oxygen itself, to generate free radicals which will attack the polyunsaturated fatty acids of membrane lipids. This oxidative deterioration of membrane lipids is known as lipid peroxidation. To protect itself against this form of attack, the organism possesses several types of defense mechanisms. Under normal conditions, these defenses appear to offer adequate protection for cell membranes, but the possibility exists that certain foreign compounds may interfere with or even overwhelm these defenses, and herein could lie a general mechanism of toxicity. This possible cause of toxicity is discussed in relation to other suggested causes.

Animals↗
PubMed1979

Developmental patterns of alcohol dehydrogenase and aldehyde dehydrogenases in homogenates and subcellular fractions of rat liver.

Both alcohol dehydrogenase (ADH) and the two isoenzymes of aldehyde dehydrogenase (ALDH-I-NAD+ and ALDH-II-NAD+) were first detected in foetal rat liver about 5 days before birth. All enzymes developed gradually and showed no abrupt increases in activity. The specific activities of ALDH-I-NAD+ and ALDH-II-NAD+ in the mitochondrial fractions, ALDH-II-NAD+ in the microsomal fractions and ADH in liver homogenates all produced a major percentage of the adult activity within a month, whereas the total activities increased over a longer part of the developmental period.

Aging↗
PubMed1979

Lipid peroxidation of the microsomal fraction and extracted microsomal lipids from DAB-induced hepatomas.

NADPH- and ascorbic acid-induced microsomal lipid peroxidation was almost absent in subcutaneously implanted DAB-induced hepatomas D23, D30 and D192A, and present at greatly reduced levels in DAB-induced primary hepatomas when compared with normal liver controls. Fatty acid analysis of the microsomal lipid from passaged tumours demonstrated adequate levels of substrate in the phospholipid fractions to support lipid peroxidation. Lipid extracted from hepatoma microsomal fractions was shown to undergo ascorbic acid-induced lipid peroxidation, but to a lesser extent that the corresponding liver extract. This may be partially explained by a decrease in the phospholipid content of hepatoma microsomal membranes. However, phospholipid extracted from microsomal fractions of hepatoma and liver supported lipid peroxidation to a similar extent. The possible role of the non-lipid component of the membrane in the process of lipid peroxidation is discussed.

Animals↗
PubMed1977

Induction of mitochondrial aldehyde dehydrogenases in livers of senescent rats.

Senescent rats were administered ethanol by gastric intubation at hourly intervals. After 1 h, there was a rapid increase in the specific activities of two isoenzymes of liver mitochondrial aldehyde dehydrogenase which was sustained for the next 2 h. No further changes were observed during the course of the following 2 h.

Aging↗