摘要:

The dependence of intestinal absorption of xenobiotics on the blood flow rate increases from blood flow independent to blood flow limited absorption as the absorbabilitiy of the substances increases. Since the absorbed substances are mainly drained by the blood flowing through the subepithelial vessels, not only the total flow rate of an intestinal segment but also the intramural blood flow pattern influences the absorption rate. The villous countercurrent exchange represents an additional resistance to the absorption. In rat jejunum a time-dependent decrease of absorption complicates the analysis of experimental data.

ISSN:0031-7012    

DOI:10.1159/000137409

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

The effects of α-adrenergic blockade with phentolamine or dibenamine on the cardiovascular response to pharmacological doses of vasopressin were studied in anesthetized dogs. Some observations were also made on the combined effects of vasopressin and norepinephrine. Changes in mean systemic arterial pressure, portal pressure, and resistance in the prehepatic splanchnic vasculature during vasopressin infusion were noted. A total of 97 dogs were used. α-Blockade appeared to enhance the response of arterial pressure to vasopressin, possibly because of loss of baroreceptor-mediated buffering action which normally attenuates its pressor action. Effects of vasopressin on mesenteric vascular resistance and portal pressure were unchanged or somewhat less after α-blockade, hence no evidence that its therapeutic effect would be improved by this combination. Vasopressin and norepinephrine when given together result in an additive pressor response with little or no evidence of potentiati

ISSN:0031-7012    

DOI:10.1159/000137410

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

Binding of ¾ouabain to Na+-K+ ATPase sites in strips of rabbit aorta was measured by kinetic analysis of washout (efflux) data. This approach allowed the separation of specific binding fron nonspecific binding including unbound extracellular glycoside. Lowering efflux temperature to 2 °C caused the rate of loss of 3H-ouabain from specific sites to be slowed (T½ = 293 min) while loss from other sites was not affected. Specificity of binding was established by: (1) a reduction of such binding in the presence of extracellular K+; (2) saturability with increasing concentration of ouabain, and (3) sensitivity to a reduction in ATP levels. Binding to Na+-K+ ATPase sites gradually reached an equilibrium during 60 min of labelling at 10–7M. At equilibrium, specific binding was 25% of the total tissue content. Half-maximal binding occurred at 5.3 X 10–8M ouabain, and binding capacity was 381 x 10–15 mol/mg dry weight under K+-free conditions. A Na+-K+ ATPase site density of approximately 74 sites/μm2 of surface membrane was calculated, based on a volume to surface area of 0.6 μm. The parameters of 3H-ouabain binding in arteries are similar to previously reported values for binding to Na+-K+ sites in intestinal smo

ISSN:0031-7012    

DOI:10.1159/000137412

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

The relative degree of absorption of methylprednisolone acetate when administered by the rectal and oral routes was studied in 12 normal male subjects. The plasma samples were assayed for methylprednisolone and endogenous hydrocortisone concentrations. After the administration of equal doses of methylprednisolone acetate by the rectal and oral routes, the plasma hydrocortisone levels were not significantly different from each other; but the plasma concentrations of methylprednisolone were significantly lower after rectal administration than after oral administration. We conclude that the practice of utilizing the degree of suppression of endogenous hydrocortisone levels as an indicator of the extent of absorption of rectally administered glucocorticoids is inappropriate.

ISSN:0031-7012    

DOI:10.1159/000137413

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

Prozime-10 (P-10), a proteolytic enzyme extracted from cultured broth of Aspergillus melleus, was injected intravenously into rats in dosages of 1-10 mg/kg and was found to alleviate carrageenin edema. Thermal denaturation diminished not only the proteolytic activity but also the antiedematous effect. Carrageenin-induced granuloma pouches in rats were reduced by P-10 in a dose-dependent manner (1–5 mg/kg). With P-10 (5 mg/kg i.v.), adjuvant arthritis was inhibited by 62% in the primary phase and by 57% in the secondary phase. Serum concentration of immunoprecipitable P-10 reached 100 mg/l within 30 min after the intraduodenal administration of P-10 (200 mg/kg) and was concomitant with a 3-fold increase in the blood esterolytic activity. When P-10 was injected (5 mg/kg i.v.) into rats, the plasma corticosterone level increased to a maximum of 4 times the preinjection level. These observations indicate that: (a) P-10 can be absorbed from the gut in sufficient quantities to bring about anti-inflammatory activity, and (b) the anti-inflammatory activity of P-10 can be related, in part, to the ability of P-10 to affect the release of glucocorticoid

ISSN:0031-7012    

DOI:10.1159/000137414

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

The effect of cartilage bone marrow extract (CBME) on the metabolism of collagen and proteoglycan in crude embryo and human cartilage was investigated. While in chick embryos’ articular cartilages the increased levels of radioactivity in collagen and proteoglycan were observed, in normal human cartilage only slight changes were detected. In osteoarthrotic cartilages, however, a marked increase in radioactivity was found in collagen and in the proteoglycan fraction containing the glycoprotein link. A blockade of collagenolysis by CBME treatment is suggeste

ISSN:0031-7012    

DOI:10.1159/000137415

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

The effect of mercuric chloride (2 mg/kg) on microsomal enzymes in mouse liver was investigated in phenobarbital- and 3-methyicholanthrene-induced hepatic microsomes. The metal caused an increase in total microsomal protein in noninduced controls, whereas no significant changes were observed in induced microsomes. Cytochrome P-450 was decreased in each case, which suggests that the metal may cause enzyme degradation. p-Nitroanisole O-demethylase was increased fivefold with both inducers. In addition, mercuric chloride increased the O-demethylase activity in relation to microsomal protein. The effect of the metal on ethylmorphine N-demethylase activity was slightly inhibitory.

ISSN:0031-7012    

DOI:10.1159/000137416

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

Isolated livers from rats fed a diet containing corn oil (10% W/W) perfused with a blood-free, modified Krebs-Henseleit solution cleared hexobarbital at a rate significantly faster than livers from rats fed a similar diet devoid of corn oil. The half-lives of hexobarbital in these experiments were 22.4 ± 1.8 min for livers from rats fed corn oil and 30.0 ± 1.2 min for those from rats fed the fat-free diet. This represented a metabolic rate of 54 μg hexobarbital/g liver/min in fat-fed animals and 36 μg hexobarbital/g liver/min in those fed a fat-free d

ISSN:0031-7012    

DOI:10.1159/000137417

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

Virgin A/J female mice were intubated daily for 8 days (short term) or 70 days (long term) with 0, 1, 5, or 25 mg/kg Δ9-tetrahydrocannabinol (Δ9-THC) or 0, 3, 15, or 75 mg/kg crude marihuana extract (CME) in a sesame oil:polysorbate 80:saline vehicle. These dosages approximate light, moderate, and heavy human usage. Short-term exposure to CME has no significant effect on PMS-HCG-induced ovulation but appears to: (1) delay entry into proestrus at all dose levels; (2) depress serum progesterone during the luteal phase at the highest CME level used (75 mg/kg), and (3) inhibit female receptivity to males at least at the highest dosage. Long-term oral administration of CME or Δ9-THC had no significant effect on length of estrous cycles or mating (plug formation) but term pregnancies were reduced by 32 and 68% for medium and high dosages, respectively. After a 30-day recovery period, 80% of those females that failed to have successful pregnancies now became pregna

ISSN:0031-7012    

DOI:10.1159/000137418

出版商:S. Karger AG    

年代:1980

数据来源: Karger

摘要:

No hepatotoxicity was demonstrated after 90 days in rats treated with two dose levels of disulfiram. A reversible inhibition of microsomal p-nitroanisole demethylase activity was found. In phenobarbital-treated rats disulfiram 100 mg/kg did not alter the induction response as indicated by the cytochrome P-450 content, but inhibited the p-nitroanisole activity to control levels. As no sign of histological liver damage was found, we conclude that the rare cases of disulfiram hepatotoxicity in man may be due to an allergic reaction.

ISSN:0031-7012    

DOI:10.1159/000137419

出版商:S. Karger AG    

年代:1980

数据来源: Karger