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Biomedical subjects

D Paul

Publications and source records attributed to D Paul.

At least 145 records · Page 8Linked to original sources
PubMed1989

Pharmacological actions of a novel mixed opiate agonist/antagonist: naloxone benzoylhydrazone.

NalBzoH (6-desoxy-6-benzoylhydrazido-N-allyl-14-hydroxydihydronomorphin one) is a novel opiate with potent actions at both mu and kappa receptors. Analgesic studies in mice examining increasing doses of NalBzoH with a fixed dose of morphine revealed a biphasic curve. NalBzoH at doses as low as 1 microgram/kg partially antagonized morphine analgesia. Higher NalBzoH doses continued to inhibit morphine analgesia in a dose-dependent manner, with the 1-mg/kg dose antagonizing completely morphine analgesia. As the NalBzoH dose increased beyond 1 mg/kg analgesia returned. NalBzoH also prduced a similar analgesic response when administered alone in mice and also was active in rats. NalBzoH had excellent p.o. activity, with an analgesic potency in mice equivalent to s.c. administration. Naloxone reversed NalBzoH analgesia far less effectively than morphine analgesia. In contrast, Win44,441 antagonized both morphine and NalBzoH analgesia with a similar potency, consistent with a kappa mechanism for NalBzoH analgesia. Repeated administration of NalBzoH resulted in tolerance. There was no analgesic cross-tolerance between NalBzoH and either morphine or the kappa 1-selective agent U50,488H, implying a selective kappa 3 mechanism of analgesia. In addition to blocking morphine analgesia, low doses of NalBzoH also partially reversed the inhibition of gastrointestinal transit in mice produced by morphine, antagonized completely morphine lethality and precipitated withdrawal in morphine-dependent mice, confirming its antagonist activity in mu receptors. The duration of NalBzoH's kappa and mu actions differed dramatically. In mice, analgesia typically lasted less than 2 hr whereas the same NalBzoH dose antagonized completely morphine analgesia, a mu action, for 16 hr. Full sensitivity to morphine did not return for 32 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

[Cellulose implants--biostability and tissue reaction].

In order to test blood detoxication systems on cellulose basis (hollow fibers as separation material) histomorphological examinations were performed after incorporation in 10 rabbits. Already after 12 days granulation tissue around the cellulose fibers was found as foreign body reaction, but the implants remain uninjured up to 86 days. The lateral stability of the hollow fibers was unchanged. Further investigations are necessary on the radial stability and the transport properties of the cellulose fibers.

Animals↗
PubMed1989

Pharmacological characterization of morphine-6 beta-glucuronide, a very potent morphine metabolite.

Morphine-6 beta-glucuronide is a major metabolite of morphine with potent analgesic actions. To define more fully the importance of this compound in morphine action, we have compared the analgesic actions of morphine and its 6 beta-glucuronide metabolite after both peripheral and central administration. Given s.c., morphine-6 beta-glucuronide elicited analgesia with an effect approximately twice that of morphine due, in part, to its long duration of action and also inhibited gastrointestinal motility. Both actions were easily reversed by naloxone (s.c.). However, when injected either i.c.v. or intrathecally, morphine-6 beta-glucuronide was approximately 90- and 650-fold more potent an analgesic than morphine, respectively. Whereas morphine in these studies was equipotent at both levels of the neuraxis as an analgesic, the 6 beta-glucuronide was approximately 5-fold more effective at the level of the spinal cord than supraspinally. The mu 1-selective antagonist naloxonazine blocked the analgesic effect of systemic and i.c.v. morphine-6 beta-glucuronide much as it blocked morphine, implying a role for mu1 receptors in these actions. Like morphine, morphine-6 beta-glucuronide analgesia after intrathecal injection was not sensitive to naloxonazine, suggesting a mu2 mechanism within the spinal cord. Together, these results imply that morphine-6 beta-glucuronide elicited its analgesic actions through the same receptor mechanisms as morphine. Mice highly tolerant to morphine after implantation of morphine pellets showed cross-tolerance to morphine-6 beta-glucuronide (s.c.). The high potency of morphine-6 beta-glucuronide strongly suggests that this metabolite plays an important role in morphine's actions.

Analgesia↗
PubMed1988

Hydrocortisone-induced accumulation of fibronectin mRNA and cell surface-associated fibronectin.

A Morris hepatoma 7777-derived cell line, DTH-3, was used to study the control of fibronectin gene expression. In cultures of DTH-3 cells in conventional medium supplemented with serum or in chemically defined MX-83 medium supplemented with insulin no cell surface fibronectin was detectable by indirect immunofluorescence techniques using specific polyclonal antibodies. By Northern blot hybridization analysis a dose- and time-dependent accumulation of 8 kb fibronectin mRNA in response to hydrocortisone treatment was demonstrated. Furthermore, 24 h after addition of hydrocortisone an extensive fibrillar fibronectin network was established. The results suggest that the hydrocortisone-dependent induction of fibronectin production might, at least in part, be controlled at the transcriptional level.

Animals↗
PubMed1988

Monocyte functional studies in asymptomatic, human immunodeficiency disease virus (HIV)-infected individuals.

Various aspects of monocyte-associated function were evaluated in the peripheral blood mononuclear cells of male homosexuals who were infected with the human immunodeficiency disease virus (HIV). The functional assessments included indomethacin-sensitive regulation of blastogenesis and lymphokine-activated killer (LAK)-cell induction, chemiluminescent responses of mononuclear leukocytes to opsonized zymosan, and the expression of HLA-DR antigen on CD-14-positive monocytes. The results obtained demonstrate that each of these functions is abnormal in asymptomatic individuals who have HIV core antigen (p24) in their circulation. These results suggest that monocyte abnormalities which could contribute to immune dysfunction in HIV-infected patients can be detected early during the course of HIV infection and are associated with the expression of serum HIV antigen.

HIV Core Protein p24↗
PubMed1988

Immortalized differentiated hepatocyte lines derived from transgenic mice harboring SV40 T-antigen genes.

Hepatocytes of transgenic mouse fetuses harboring SV40 virus transforming gene sequences in the SV delta e-MGH fusion gene construct 202 driven by the mouse metallothionein (MT-I) enhancer [R. D. Palmiter, H. Y. Chen, A. Messing, and R. L. Brinster (1985) Nature (London) 316, 457-460] were cultured at Day 19 of gestation and established as a differentiated line expressing albumin and alpha-fetoprotein (AFP) mRNAs. Hepatocyte line FMH-202 contains integrated SV40 sequences, expresses SV40 T-antigen genes, and exhibits unlimited growth potential because it has been cultured 18 months without apparent decrease in cell viability or in growth rate that could suggest the occurrence of a crisis period. Immortalized cells multiply in chemically defined medium deficient in arginine with transferrin plus insulin, whereas EGF, insulin, and transferrin are obligatory requirements for fetal or newborn mouse hepatocyte multiplication in primary cultures. Cells did not grow in agar and were not tumorigenic in nude mice. Their immortalized, nonmalignant phenotype was further documented by low saturation densities of confluent monolayers showing no overgrowth, and by growth arrest in the absence of insulin with subsequent induction of DNA synthesis and resumption of cell growth in response to insulin. Thus, it appears that immortalized SV40 T-antigen-expressing hepatocytes are present in the liver of the transgenic mice. However, at later points in liver development the transforming activity of T-antigen becomes apparent and leads to hepatocellular carcinoma formation in vivo.

Animals↗
PubMed1988

Attenuation of morphine analgesia by the S2 antagonists, pirenperone and ketanserin.

The involvement of serotonin type-2 (S2) receptors in morphine-induced analgesia was assessed by challenging the effect of 10 mg/kg of morphine sulphate (IP) with the S2 receptor blockers, pirenperone and ketanserin. Tail-flick latencies were assessed at 0, 30, 60, 90 and 120 min after injections by measuring the time that it took each rat to remove its tail from a 52 degrees C water bath. Pirenperone, at 0.08, 0.16, and 0.24 mg/kg (SC) attenuated morphine-induced antinociception. In contrast, only the high 10 mg/kg (SC) dose of ketanserin attenuated the effect of morphine. Because pirenperone easily enters the central nervous system whereas ketanserin does not, these results indicate the involvement of central S2 receptors in morphine-induced antinociception. The 10 mg/kg dose of ketanserin, however, did not attenuate the antinociception produced by 100 mg/kg of ketamine. Thus, the antianalgesic effect of S2 receptor blockers may be specific to opioid-mediated analgesia.

Analgesia↗
PubMed1988

Plasma glutathione S-transferase concentration as a measure of hepatocellular integrity following a single general anaesthetic with halothane, enflurane or isoflurane.

The plasma concentration of hepatic glutathione S-transferase (GST) was measured in matched groups of patients who received halothane, enflurane or isoflurane anaesthesia for elective minor surgery. The GST concentrations increased significantly at 3 h after anaesthesia in patients who received halothane or enflurane, but not in patients who were given isoflurane. A secondary increase in GST concentration, at 24 h, was seen in a small number of individuals who received halothane or enflurane. Abnormal GST concentrations were found in 50% of patients following halothane anaesthesia, 20% following enflurane and 11% after isoflurane. The small but significant increases in GST concentrations in patients receiving halothane or enflurane suggests an impairment of hepatocellular integrity following the administration of these anaesthetics. In contrast, isoflurane anaesthesia did not appear to be associated with this effect.

Adult↗
PubMed1988

Comparison of antigen immunoassay and reverse transcriptase assay for monitoring human immunodeficiency virus infection in an antiviral trial.

We compared the Abbott enzyme immunoassay for human immunodeficiency virus (HIV) antigen with the reverse transcriptase assay (RTA) as a means of monitoring HIV infection during an antiviral trial. The Abbott enzyme immunoassay detected HIV earlier than RTA whether or not the patients were antigenemic and appears to be superior to RTA for detecting HIV in cultures used for monitoring clinical trials.

AIDS-Related Complex↗
PubMed1988

Mental health promotion in the local community service centres in Quebec.

The definition of the concepts of mental health and mental health promotion have been much discussed in Quebec for a number of years. The authors of this article present their point of view on the role the Local Community Service Centres (LCSCs) could play in implementing a mental health action plan. On the basis of a definition of the concepts of mental health and mental health promotion and an outline of the goals and objectives of mental health promotion, the authors discuss certain areas of intervention for the various sectors of practice in the LCSCs. Their article closes with some cautions about the limitations of health promotion in the LCSCs.

Community Mental Health Centers↗
PubMed1988

Immortalization and malignant transformation of hepatocytes by transforming genes of polyoma virus and of SV40 virus in vitro and in vivo.

Hepatocytes can be converted into permanently growing hepatocyte lines by the transforming genes of either polyoma virus or SV40 virus. In transgenic mice harboring SV40 virus sequences (strain 202) most of the hepatocytes in the liver during late fetal development display an immortalized phenotype in culture, which is apparent immediately after placing liver cells into primary cultures. We conclude that at the late fetal stage hepatocytes in the liver display similar properties which might be the "initiated" cell type discussed earlier, and while untransformed, is determined to become malignant at a later point in development. Immortalized hepatocyte lines derived from the transgenic animals display reduced growth factor requirements in culture, i.e., increased autonomy. With time in culture, cells become increasingly autonomous by further reduction of their growth requirements until the final autonomous state has been attained, i.e., growth in the absence of any growth factor or hormone. It remains to be seen whether the development towards HCC in the normal liver is accompanied by a similar increased autonomy of growth factors, as observed in cells in culture.

Animals↗
PubMed1988

Altered growth factor requirements and cell cycle control in rat hepatoma cells versus adult rat hepatocytes in culture.

Adult rat hepatocytes multiply in primary cultures when incubated in arginine-free MX-83 medium supplemented with dialyzed fetal calf serum, insulin, glucagon, hydrocortisone, epidermal growth factor, and transferrin. In the absence of mitogens, the fraction of the cells engaged in DNA synthesis dropped sharply. However, cells initiated DNA synthesis in response to the mitogenic mixture indicating that hepatocyte proliferation is controlled by G1----S transition rates. In contrast, rat hepatoma line DTH-3, derived from Morris 7777 "minimal deviation" hepatoma, required only insulin for proliferation in chemically defined MX-83 medium. The lengths of their cell cycle phases varied with the growth rate. The phases of the growth cycle were proportionately shortened (expanded) when the growth rate was increased (decreased). It is concluded that DTH-3 hepatoma cells, which display a decreased growth factor requirement as compared with adult rat hepatocytes differ from normal hepatocytes by fundamental alterations in the mechanisms controlling the progression of the cell cycle.

Animals↗
PubMed1988

[Results of the chronic compression of visceral arteries in animal experiments].

Occlusions of different visceral arteries were imitated by progressive swelling substance constriction in 30 mongrel dogs. The variants of the developed collateral circulation could be proved by the postoperative angiographies. There is given reference to the importance of the connections of the visceral vascular system among one another and for the abdominal surgery of the human. Evidence is given that occlusions of the celiac artery and of the superior mesenteric artery are compensable only with the formation of large collateral vascular systems. But on certain circulation conditions the inferior mesenteric artery has a great significance too.

Animals↗