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Biomedical subjects

J M Sneddon

Publications and source records attributed to J M Sneddon.

At least 19 recordsLinked to original sources
PubMed1991

A pharmacokinetic and dynamic study of single nightly doses of conventional and controlled release formulations of trazodone.

We studied the pharmacokinetics and dynamics of single evening oral doses of conventional capsules (100 mg) and a controlled release formulation (150 mg) of trazodone in 12 fasting and non-fasting young healthy volunteers. When corrected for the different doses used, there was no significant difference among the areas under the plasma concentration-time curves (AUC) for the conventional capsules and the controlled release tablets under fasting and non-fasting conditions. Both conventional and controlled release formulations were followed by a reduction in critical flicker fusion threshold (CFFT) and this effect was not influenced by the administration of food before dosing. After both conventional and controlled release formulations, blood pressure was significantly lower when medication had been given in the fasting state than when it had been given after food. The frequency of adverse symptoms was greater after the controlled release (150 mg) than after the conventional (100 mg) formulation. We conclude that there is no obvious advantage to the controlled release formulation (150 mg) and that conventional trazodone (100 mg) should be taken after food when it is given at night.

Adult↗
PubMed1989

Enhanced endothelial cytopathogenicity induced by a cytomegalovirus strain propagated in endothelial cells.

Endothelial involvement has been implicated in cytomegalovirus (CMV) infection, a source of major complications in immunosuppressed individuals (e.g., those with acquired immune deficiency syndrome [AIDS] and organ transplants). Traditionally, CMV has been grown in fibroblasts; however, propagation in these cells may alter characteristics of the virus. In developing an in vitro model system of CMV/endothelial cell interaction, we have addressed this issue by propagating a clinical isolate, CMV VHL 1, in human umbilical vein endothelial (HUVE) cells by serial cocultivation of heavily infected cultures with fresh HUVE monolayers and have compared its infectious properties with those of the fibroblast-raised strain, CMV AD169. In situ hybridization using a biotinylated DNA probe, as well as immunofluorescent staining for CMV-specific antigen, has confirmed infection of HUVE cells inoculated with either strain of the virus. Infection of HUVE by VHL was accompanied by dramatic cytopathology not observed in AD169-infected cells. Plaque assay of culture supernatants revealed greater virus production in VHL-infected HUVE as compared with equivalently inoculated fibroblasts. In contrast, AD169 production in inoculated fibroblasts exceeded that in HUVE. These studies demonstrate the suitability of cultured endothelial cells as a substrate for CMV propagation and suggest that a strain of virus thus propagated may offer an accurate model of CMV/endothelial cell interaction in human disease.

Cells, Cultured↗
PubMed1989

Superoxide anions enhance platelet adhesion and aggregation.

1. Superoxide dismutase (SOD, 60 u ml-1) or ferricytochrome c (70 microM) significantly inhibited thrombin-stimulated platelet adhesion to gelatin-coated plastic, whereas catalase (1000 u ml-1) or mannitol (1 mM) had no effect. 2. The platelet aggregation induced by low concentrations of thrombin (causing less than 45% maximal change in light transmission) was inhibited by SOD. Catalase or mannitol had no effect on platelet aggregation. 3. Pyrogallol (an O2- generator) enhanced both platelet adhesion to gelatin-coated plastic and platelet aggregation induced by thrombin; this enhancement was neutralized by SOD. 4. These results indicate that O2- increase both platelet adhesion and aggregation, whereas other free radicals such as hydrogen peroxide or hydroxyl radicals are not involved.

Adenine↗
PubMed1989

Cytomegalovirus infection of gastrointestinal endothelium demonstrated by simultaneous nucleic acid hybridization and immunohistochemistry.

To demonstrate the degree of involvement of endothelial cells in cytomegalovirus (CMV) infection of the gastrointestinal tract we have stained sections from gastrointestinal specimens that showed inclusion bodies on hematoxylin-eosin staining. Factor VIII was first detected using a rabbit anti-factor VIII primary antibody and an alkaline phosphatase-labeled sheep anti-rabbit secondary antibody. The CMV was then visualized with a biotin-labeled CMV probe detected by a streptavidin peroxidase technique with aminoethyl carbazole as the chromogen. Factor VIII staining was a bright blue and CMV a brick red. The specimens included one small-bowel resection and four colonic resections, as well as an esophageal biopsy. The patients' diagnoses included bone marrow transplant recipient, acquired immunodeficiency syndrome, ulcerative colitis, and renal transplant recipient. Cells positive for both CMV and factor VIII ranged from 35% to 60% of positive cells in a representative section, and the relative percentages (mean +/- SE) for cell type for infected cells were: endothelial, 48.9 +/- 4.5; vascular luminal (factor VIII negative), 6.1 +/- 1.7; perivascular (factor VIII negative in vascular wall), 16.2 +/- 3.2; and other cell (non-vascular factor VIII negative), 28.9 +/- 5.1. These findings and clustering of infected cells around the vessels provide evidence that CMV infection of the gastrointestinal tract is primarily vasculitic and related to infection of endothelial cells.

Adult↗
PubMed1988

Endothelium-derived relaxing factor reduces platelet adhesion to bovine endothelial cells.

The adhesion of thrombin-stimulated human blood platelets to either the endothelial surface of intact bovine aorta or cultured bovine aortic endothelial cells was studied to determine the role of endothelium-derived relaxing factor in the regulation of platelet adhesion. Endothelial cells and platelets were pretreated with indomethacin to prevent the formation of prostaglandins. The adhesion of thrombin-stimulated platelets to endothelial cells was reduced by superoxide dismutase and bradykinin. The inhibitory effect of both drugs was abolished by hemoglobin and was absent in strips of bovine aorta where the endothelial cells had been removed by scraping. It is suggested that the effects of bradykinin are mediated by the release of endothelium-derived relaxing factor, which is protected from destruction by superoxide dismutase, and that endothelium-derived relaxing factor contributes to the nonadhesive properties of the vascular endothelium.

Adenine↗
PubMed1988

Unexpected death in an infant with AIDS: disseminated cytomegalovirus infection with pancarditis.

Cardiac involvement in patients with acquired immunodeficiency syndrome (AIDS) is being reported with increasing frequency, although the factors responsible for the cardiac abnormalities are rarely identified. We report a case of sudden and unexpected death of an infant with AIDS in whom histologic and virologic studies documented generalized infection with cytomegalovirus (CMV), including pancarditis, sialitis, nephritis, colitis, hepatitis, prostatitis, orchitis, myositis, pneumonitis, and meningoencephalitis. CMV was isolated from four of five tissues cultured. Lymphocytic infiltration in the region of the sinoatrial node could have been responsible for the development of a fatal cardiac arrhythmia, and the autopsy failed to reveal any other cause of death in this infant. Children infected with the human immunodeficiency virus (HIV) need to be closely monitored for cardiac complications bearing in mind that opportunistic infections in AIDS patients may cause cardiac involvement that is atypical or that is overshadowed by the primary manifestations of the infection.

Acquired Immunodeficiency Syndrome↗
PubMed1988

In situ DNA hybridization for cytomegalovirus in colonoscopic biopsies.

We reviewed colonoscopic biopsies of the lower gastrointestinal tract performed during a two-year period. Those representing neoplasia were excluded. Formalin-fixed paraffin-embedded biopsy specimens from 53 patients were studied by in situ DNA hybridization for cytomegalovirus (CMV) using commercially available biotinylated DNA probes detected by an avidin-biotin peroxidase technique. Nine of the patients were severely immunocompromised: four had acquired immunodeficiency syndrome, three had ulcerative colitis and were receiving high-dose steroid therapy, one was a bone marrow transplant recipient, and one had idiopathic pulmonary fibrosis and was receiving therapy with prednisone and cyclophosphamide. Four of these had evidence of CMV infection by routine histology and DNA hybridization. Three additional immunocompromised patients had evidence of CMV infection by DNA hybridization alone. Forty-four patients had inflammatory conditions or ulcerations of the lower gastrointestinal tract. Six of these had evidence of CMV by DNA hybridization alone. Histologically normal as well as enlarged and cytomegalic cells were probe positive, and the cells were sparse to numerous in number. They were found in the epithelium and/or lamina propria. This technique was demonstrated to be applicable to routinely processed colonic biopsy specimens.

Adult↗
PubMed1985

The effect of ions on the adhesion and internalization of Chlamydia trachomatis by HeLa cells.

The adhesion and internalization of Chlamydia trachomatis by HeLa cells was unaffected by removal of K+, Mg2+, or glucose from the incubation medium, slightly reduced by removal of Na+, and significantly reduced by omission of Ca2+, Sr2+, Mg2+, and Mn2+ could replace Ca2+ in the adhesion but only Sr2+ supported internalization, and La3+, Co2+, Fe3+, Ba2+, and Zn2+ all reduced internalization more than adhesion. During initial infection there was no measurable difference in the uptake or release of 45Ca2+ or 86Rb+ between infected and noninfected HeLa monolayers. Infection was not prevented by pretreatment of the monolayers with the calcium channel blockers, verapamil, D600, and nitrendipine, or the calmodulin inhibitors, TMB-8 or trifluperazine. The results suggest that divalent cations are not essential for chlamydial infection but that the process of internalization is facilitated by the presence of cations, particularly Na+ and Ca2+.

Adhesiveness↗
PubMed1984

Decreased calcium content and 45Ca2+ uptake in Down's syndrome blood platelets.

Total intracellular Ca2+ and 45Ca2+ uptake has been studied in blood platelets from subjects with Down's syndrome and matched controls. In Down's subjects, Ca2+ levels (85.5 +/- 5.9 nmol/10(-9) platelets) were significantly lower than controls, 174 +/- 10.0 nmol/10(-9) (p less than 0.0005). A similar reduction was seen in calcium uptake (Down's platelets, 0.79 +/- 0.06 nmol/10(-9) platelets; controls, 1.17 +/- 0.07 nmol/10(-9) platelets, p less than 0.005). The low levels of intracellular Ca2+ may be related to decreased granular storage of serotonin, and the decreased Ca2+ uptake with impaired transport by intracellular Ca2+-accumulating organelles such as the dense tubular system.

Adult↗
PubMed1975

The influence of metyrapone on the synthesis and release of prostaglandins from the pregnant rat uterus in vitro.

1 Metyrapone (150 mg/kg, s.c. or i.p.) an inhibitor of corticosteroid biosynthesis, significantly reduced the release of prostaglandins of the F-type from isolated preparations of pregnant rat uteri in vitro, on day 22 - the expected day of delivery. 2 Metyrapone and indomethacin administered in vitro both inhibited the conversion of 14C-arachidonic acid to prostaglandin E2 by homogenates of day 22 pregnant rat uteri. Metyrapone was approximately 150 times less potent than indomethacin. Although indomethacin also inhibited prostaglandin F2alpha production, metyrapone stimulated synthesis of this prostaglandin. The differential inhibition of prostaglandin synthesis by metyrapone may reflect sensitivity of the inhibitor to changes in experimental conditions. 3 Inhibition of prostaglandin synthesis may explain the effects of metyrapone on parturition in the rat.

Animals↗
PubMed1975

Evidence for a possible foetal control of prostaglandin release from the pregnant rat uterus in vitro.

The release of prostaglandin-like material and these spontaneous contractions of individual horns from the pregnant rat uterus in vitro have been studied on day 22 of pregnancy - the expected day of delivery. Removal of foetuses (retaining placentae in utero) from one or both uterine horns on day 16 or 17 significantly reduced prostaglandin F release and spontaneous activity. Rats which had been made unilaterally pregnant after ligation of one uterine horn, exhibited a decrease in prostaglandin F output from both horns. Uterine activity and prostaglandin release were increased in quiescent uteri by the addition of arachidonic acid (5 mug/ml) or phospholipase A (160 mu./ml); the effects were abolished by indomethacin (20 mug/ml). However, the stimulation of uterine activity by PGF2alpha (30-60 ng/ml) was not affected by indomethacin. It is concluded that the release of prostaglandins from the pregnant rat uterus in vitro at term is related to the presence of viable foetuses.

Animals↗
PubMed1974

Effect of selective proteolysis on the accumulation of 5-hydroxytryptamine by intact rat blood platelets.

1 The effect of perturbation of intact blood platelets with proteolytic enzymes was studied with respect to 5-hydroxytryptamine (5-HT) transport, adenine transport and intracellular Na(+) and K(+) levels.2 Leucine aminopeptidase and thrombin reduced 5-HT transport, released 5-HT from pre-labelled platelets and disturbed the gradient to monovalent cations. Leucine amino-peptidase, but not thrombin, inhibited adenine transport.3 alpha-Chymotrypsin and carboxypeptidases A and B were without effect on the parameters studied.4 Trypsin selectively reduced 5-HT transport. It did not release 5-HT from blood platelets or inhibit adenine transport.5 The action of proteolytic enzymes is discussed in terms of proteins localized in the external membrane that may function in part as membrane carriers.

Adenine↗