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Biomedical subjects

D A Lewis

Publications and source records attributed to D A Lewis.

At least 289 records · Page 16Linked to original sources
PubMed1984

The anti-ulcerogenic activity of the unripe plantain banana (Musa species).

Various preparations of dried unripe plantain banana were found to be anti-ulcerogenic against aspirin-induced ulceration in the rat and were effective both as a prophylactic treatment and in healing ulcers already induced by aspirin. Ripe fruit bananas were inactive. The active factor(s) were water soluble and were concentrated by extraction to approximately three hundred times that in the dried banana powder. The anti-ulcerogenic action of banana preparations appears to be due to their ability to stimulate the growth of gastric mucosa. Aluminium hydroxide, cimetidine, prostaglandin E2, N6, O2-dibutyryl adenosine 3',5' cyclic monophosphate but not 5-hydroxytryptamine were also anti-ulcerogenic when used prophylactically in rats but were ineffective in healing ulcers already formed by aspirin. These substances did not stimulate the growth of gastric mucosa.

Aluminum Hydroxide↗
PubMed1984

Serotonergic stimulation of adrenocorticotropin secretion in man.

Controversy still exists regarding the role of serotonin in the regulation of ACTH secretion. We gave normal men three oral doses (0.5, 1.0, and 1.5 mg/kg) of fenfluramine, a serotonin-releasing agent and uptake inhibitor, and a corresponding placebo. There was a significant dose-dependent stimulatory effect of fenfluramine on both ACTH and cortisol levels. After the highest dose of fenfluramine, mean ACTH and cortisol levels increased from 20.8 pg/ml and 7.3 micrograms/dl to 35.5 pg/ml and 15.1 micrograms/dl, respectively. In a separate study, normal men were pretreated with cyproheptadine, a serotonin antagonist, before the administration of fenfluramine. Cyproheptadine did not significantly alter basal ACTH or cortisol levels, but it did blunt the responses of both hormones to fenfluramine. Cyproheptadine pretreatment did not alter plasma levels of fenfluramine. These findings support a stimulatory role for serotonin in the regulation of ACTH secretion in man.

Adrenocorticotropic Hormone↗
PubMed1984

Analysis of the specificity of physostigmine stimulation of adrenocorticotropin in man.

Five normal men were given infusions of saline and three doses (6, 12, and 18 micrograms/kg) of physostigmine, a centrally acting anticholinesterase, after pretreatment with glycopyrrolate, a peripheral cholinergic antagonist. There was no increase in basal ACTH or cortisol concentrations in any of the subjects after saline or the two smaller doses of physostigmine. However, each subject had a marked increase in ACTH and cortisol levels after the largest dose of physostigmine. These changes were preceded in each subject by the occurrence of noxious side effects and were accompanied by a rise in PRL levels in four of the subjects. Four subjects who received physostigmine (12 micrograms/kg) without glycopyrrolate pretreatment also experienced noxious side effects; these symptoms were followed by elevations in ACTH, cortisol, and PRL levels. These findings suggest that physostigmine stimulates ACTH and cortisol secretion through a stress-mediated effect rather than through a specific cholinergic mechanism. Consequently, physostigmine is not a reliable tool for investigating the cholinergic regulation of ACTH and cortisol.

Adrenocorticotropic Hormone↗
PubMed1983

Stereoselectivity and regioselectivity of uridine-5'-diphosphoglucuronosyltransferase toward vicinal dihydrodiols of polycyclic aromatic hydrocarbons.

The ability of a purified rat liver microsomal uridine-5'-diphosphoglucuronosyltransferase to catalyze the glucuronidation of stereoisomeric trans- and cis-9, 10-dihydroxy-9, 10-dihydrophenanthrenes and 4, 5-dihydroxy-4,5-dihydrobenzo[alpha]pyrenes is examined. The enzyme shows the ability to discriminate kinetically between the antipodes of trans-9, 10-dihydroxy-9, 10-dihydrophenanthrene with turnover numbers of 0.070 and 1.4 s-1 and kc/Kmapp values of 4.4 X 10(3) and 1.1 X 10(3) M-1 s-1 for the 9R, 10R and 9S, 10S stereoisomers. Glucuronidation of the nondissymmetric cis-9, 10-dihydroxy-9, 10-dihydrophenanthrene proceeds with a turnover number of 0.037 s-1 and kc/Kmapp of 18 X 10(3) M-1 s-1 to give a 60/40 mixture of the two possible diastereomeric products. Three of the four stereoisomers of 4,5-dihydroxy-4,5-dihydrobenzo[alpha] pyrene are regioselectively glucuronidated by the enzyme with a high degree of kinetic discrimination. Turnover numbers for the 4S,5S, 4R,5R, and 4S,5R stereoisomers are 4.1, 0.37, and 0.23 s-1 with kc/Kmapp values of 23.8 X 10(3), 0.23 X 10(3), and 3.15 X 10(3) M-1 s-1, respectively. The 4R,5S cis isomer is not a substrate. Enzyme-catalyzed reactions of the 4S,5S and 4S,5R isomers give exclusively (greater than or equal to 95%) the 4-glucuronide with the 4R,5R isomer giving the 5-glucuronide. The kinetic and regiochemical results indicate that the enzyme recognizes hydroxyl groups on the beta-face or bottom face of the 4,5-dihydroxy-4,5-dihydrobenzo[alpha]pyrenes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Infection with netilmicin resistant Serratia marcescens in a special care baby unit.

An outbreak of colonisation and infection with a netilmicin resistant strain of Serratia marcescens occurred in a special care baby unit. S marcescens was isolated from a total of 13 babies; significant infection occurred in five, of whom two died. Epidemiological investigation failed to detect a common source but gastrointestinal colonisation of babies formed a prolonged and possibly important reservoir for infection. Containment proved difficult until the unit was closed to new admissions, and even then spread to a temporary unit ensued. O Serotyping and bacteriophage typing disclosed a single epidemic strain. This produced an aminoglycoside acetylating enzyme (AAC(6')) conferring resistance to netilmicin and tobramycin and moderate resistance to amikacin. Use of gentamicin resulted in the isolation of serratia with increased resistance to all aminoglycosides, and, similarly, increased resistance to third generation cephalosporins emerged with their use.

Acetyltransferases↗
PubMed1983

The use of corticosteroids encapsulated in erythrocytes in the treatment of adjuvant induced arthritis in the rat.

Corticosteroid esters have been encapsulated into intact erythrocytes and used as an intravenous treatment for adjuvant induced arthritis in the rat. The treatment consisted of injections of the encapsulated steroids with the effects monitored for up to 14 days. On an equivalent weight basis both encapsulated cortisol-21-phosphate and prednisolone-21-sodium hemisuccinate proved superior to the free steroid esters administered in solution by injection.

Acute Disease↗
PubMed1983

Encapsulation of drugs in intact erythrocytes: an intravenous delivery system.

A number of drugs and the plasma antiprotease alpha 1-antitrypsin has been encapsulated in intact erythrocytes after hypotonic swelling, using a technique designed to preserve the viability of the cells. By labelling the cells with fluorescein isothiocyanate it has been shown that the cells survive exceptionally well when returned to the animal's circulation. Cell survival has been demonstrated in the rat, rabbit and guinea-pig. With encapsulation of cortisol-21-phosphate and methotrexate it was found that blood levels of the drug were maintained for a longer period than when the free drug was administered. Cortisol-21-phosphate was hydrolysed enzymatically by acid phosphatase located primarily in the erythrocyte membrane. An in vitro test involving the interaction or erythrocytes with phagocytes was developed to determine the viability or erythrocytes after being subjected to the encapsulation process. Preparations which did not interact with phagocytes survived when returned to the animal's circulation. The encapsulation procedure increased the fragility of the cell membrane compared to that of normal cells as measured by the leakage of haemoglobin after thermal treatment but it was found that encapsulated cortisol-21-phosphate in cells actually stabilized the membrane. The electrical charge on the membrane of encapsulating cells was the same as that of the normal cells. The charge on reformed ghosts was lower than that of normal cells. Reformed ghosts were rapidly removed when introduced into the circulation. The encapsulation procedure and its possible applications are discussed.

Animals↗
PubMed1983

Differentiation of depressive subtypes by insulin insensitivity in the recovered phase.

The glucose response to a standard insulin tolerance test (ITT) has been reported to be blunted in the acute phase of heterogeneous depressive disorders and to be normal in the recovered phase. We studied the glucose response to ITT in the recovered phase depression in patients who had previously been subclassified according to familial and clinical characteristics. All patients with depressive spectrum disease had an adequate glucose response to the ITT, whereas only 40% of patients with familial pure depressive disease and 56% of patients with bipolar illness had an adequate hypoglycemic response. There was also a trend toward a decrease in insulin sensitivity in patients who had been nonsuppressors to dexamethasone when depressed. These findings suggest that the glucose response to ITT may be a useful tool in differentiating among the heterogeneous depressive disorders.

Adult↗
PubMed1983

Induction of colon mucosal beta-glucuronidase production as a mechanism for 1,2-dimethylhydrazine colon carcinogenesis.

Although early studies in germ-free rats showed almost complete dependence on dimethylhydrazine (DMH) colon carcinogenesis upon the presence of colon bacteria, no adequate explanation was given for the 20% tumor incidence observed in germ-free animals. Bacterial activation of liver microsomal products releasing active proximate carcinogens has been the accepted reason for the exquisite specificity DMH has for the colon. Recent work, including the present study, show the colon mucosa is capable of metabolizing carcinogens and activating conjugating forms metabolized in the liver independent of the intestinal microflora. Mucosal beta-glucuronidase production was assayed in coded, scraped mucosa samples from the duodenum/jejunum, ileum, right colon, and left colon of normal and DMH-treated rats. Normal mucosal beta-glucuronidase production was highest in the left colon followed by the right colon, duodenum, and ileum, respectively. Enzyme production in the left colon was significantly increased 24 hours after injection of 25 mg/kg body weight DMH. No elevation was seen in other mucosal samples. Metabolism of DMH to oxidated forms conjugated to glucuronic acid is well established. Thus, this study offers a possible role for carcinogen, induction of a metabolic enzyme in its target tissue.

Animals↗
PubMed1983

Peritoneal cell responses to acute gastro-intestinal inflammation.

Cell changes in the peritoneal exudate induced by an acute localised inflammation due to a small intestinal anastomosis have been studied. The maximum response occurs on the second day. The neutrophil polymorphonuclear leucocyte output on the second is seven times greater in the peritoneal exudate than in the effluent lymph from the gastro-intestinal tract. The fate of the inflammatory cell response of the peritoneal exudate has been studied using thymidine-labelled cell transfer experiments. Some neutrophil polymorphonuclear leucocytes and eosinophils are phagocytosed by monocyte/macrophage cells in the peritoneal cavity. The majority of the neutrophil polymorphonuclear leucocytes and eosinophils migrate through diaphragmatic "stomata" to the parathymic lymph glands via the mediastinal lymphatics.

Acute Disease↗
PubMed1983

Putrescine--a potent endogenous anti-inflammatory substance in inflammatory exudates.

Sponge-induced exudate from the rat and saline extracts of normal rat liver and rat liver damaged in situ by dimethylnitrosamine have been assayed for putrescine, spermidine and spermine levels. The three physiological oligoamines have been examined for anti-inflammatory activity by the carrageenan-induced oedema rat model and spermidine and putrescine were found to be anti-inflammatory with putrescine being about ten times as active as spermidine. Putrescine was also anti-inflammatory in the adjuvant arthritic rat model. Thioacetamide and theophylline were also anti-inflammatory and theophylline doubled the level of putrescine in rat liver. It was concluded that putrescine was a potent anti-inflammatory factor in the inflammatory exudates and extracts examined.

Animals↗
PubMed1983

Anti-inflammatory factors in sponge-induced exudate in the rat.

Sterile polyester sponge-induced exudates in the rat have been investigated for high molecular weight substances with anti-inflammatory activity against carrageenan-induced oedema in the rat. The only substances found with this activity were dialysable molecules. Crude but sterile protein fractions isolated from exudate stabilized guinea-pig macrophages at low concentrations. The proteins present in exudates appeared to be identical to normal rat plasma proteins. It is concluded that anti-inflammatory activity associated with high molecular substances in exudate may have been due to bacterial contamination.

Acid Phosphatase↗
PubMed1983

Mechanical properties of the tibia from chickens with idiopathic scoliosis.

The tibia from six-week old chickens that develop idiopathic scoliosis were studied with stress relaxation experiments and torsional strength testing. Most parameters observed did not show any significant differences between tibias obtained from chickens with scoliosis and tibias from the control birds; however, the rate of stress relaxation of the tibia from the birds with scoliosis was minimally increased over the controls. There were no significant differences noted in ultimate torsional strength, maximum angular deformity or modulae of torsional rigidity of the tibias from scoliotic chickens when compared to tibias from control chickens.

Animals↗
PubMed1983

Steroid-induced psychiatric syndromes. A report of 14 cases and a review of the literature.

Although it is well-established that psychiatric symptoms can develop in association with the administration of corticosteroids, the nature of this relationship is poorly understood. We reviewed 14 previously unreported cases of steroid-induced psychiatric syndromes, 79 cases from the literature and 29 studies of the clinical efficacy of steroids in various medical illnesses. Our findings indicate that severe psychiatric reactions occur in approximately 5% of steroid-treated patients, and that a large proportion of these patients have affective and/or psychotic symptoms. Psychiatric disturbances usually occur early in the course of steroid therapy. Female sex, systemic lupus erythematosus and high doses of prednisone may be risk factors for the development of a steroid-induced psychiatric syndrome. Treatment with steroid-taper, neuroleptics or electroconvulsive therapy is generally effective, although tricyclic antidepressants do not appear to be useful therapeutic agents. Most patients recover within several weeks of the onset of symptoms.

Adolescent↗