Alcoholics with fatty liver had a reduced P-450 content, but the total amount of P-450 and the antipyrine half-life were normal. The results demonstrate in alcoholics that an enlarged liver of normal histological appearance is associated with enhanced drug metabolism. In subjects with fatty liver the drug metabolizing capacity per unit weight of liver is often impaired, but the increase in liver size leads to undisturbed total oxidizing capacity and normal in vivo metabolism.
In alcoholic hepatitis drug metabolism is impaired in spite of hepatomegaly. In cirrhosis the enlargement of the liver appears to compensate for the decreased P-450 content resulting in only slightly decreased total P-450, and the severly impaired in vivo drug metabolism may be due to derangement of blood flow.
The influence of a high plasma concentration of hydrocortisone on the metabolism of phenazone in humans has been studied. Two series of experiments were carried out, Group A to demonstrate any enzyme-inducing effect of hydrocortisone, and Group B to study the immediate effect of hydrocortisone on the metabolism of phenazone.
9 subjects (Group A) received a total 250--400 mg hydrocortisone i.m. twice daily for three days and the 24-hour elimination of phenazone was studied before and afterwards. In a further 5 subjects (Group B) the elimination of phenazone was examined during administration of hydrocortisone of placebo. The elimination rate and the apparent volume of distribution of phenazone remained unchanged under both experimental conditions. Evidence has been presented to show that chemokinesis and chemotaxis of human neutrophil granulocytes can be controlled by distinct cellular mechanisms and by different chemicals.
Materials such as human serum albumin or fibrinogen had chemokinetic but no chemotactic properties. Highly purified preparations of serum-derived peptides containing classical anaphylatoxin had detectable chemotactic activity only. Chemokinetic as well as chemotactic substances were required for the expression of chemotaxis in the form of efficient directional locomotion. The roles of chemokinesis and chemotaxis in the regulation of directional locomotion have been analyzed. Further experiments showed that the chemotactic response conforms to the law of Weber-Fechner.
The number of cells which had accumulated in response to a chemotactic simulus was proportional to the logarithm of the concentration of the chemical substance. Readaptation from high to low chemotactic stimulus occurred only to a limited extent. This report describes model systems which show low primary in vitro syngeneic cytotoxic responses to a Moloney-induced YAC tumor (syngeneic in A mice) and a Rauscher-induced RBL5 tumor (syngeneic in C57BL/6 mice) and examines different approaches to overcome these defects.
Two major findings were obtained: (a) spleen cells from A mice, injected with tumor cells from an in vitro tumor line YAC-1, derived from YACL, could generate a significant syngeneic cytotoxic response. In contrast, spleen cells from A mice injected with tumor cells from the in vivo tumor line failed to generate a syngeneic cytotoxic response. Thus, tumor cells from the in vitro line were more immunogeneic that those from the in vivo line. (b) Spleen cells from A mice which were injected with the cross-reactive allogeneic tumor RBL5, could generate significant cytotoxic responses to the syngeneic tumors YAC and YAC-1.
Similarly, spleen cells from C57BL/6 mice injected with the cross-reactive allogeneic tumor YAC-1, could generate a significant cytotoxic response to the syngeneic tumor RBL5. Thus, cross-reactive allogeneic tumors could stimulate syngeneic cytotoxicity. The theoretical and the practical implications of these studies are discussed.
The effects of mazindol, a non-phenethylamine anorexic, were determined in pigeons key pecking under a multiple fixed-ratio 30 response, fixed-interval 5 min schedule of food presentation. The low average rates of responding under the fixed-interval schedule were greatly increased (from 0.7 response/sec to 2 responses/sec) at doses from 0.1 to 10 mg/kg. The higher rates of responding under the fixed-ratio schedule were only decreased by increasing doses of mazindol.
Throughout the fixed interval, mazindol tended to produce a constant rate of responding completely disrupting the normal, positively accelerated pattern of responding. These rate-increasing effects of mazindol were much greater than those of phenethylamines tested under similar conditions. The large increases in rates of responding under the fixed-interval component were discussed in terms of the known biochemical effects of mazindol. Intact ICR mice receiving Triamcinolone showed extensive proliferation within the mammary gland. In contrast with the non-treated animals, those treated with Triamcinolone had an evident lobuloalveolar system. Triamcinolone failed to activate the glands of oophorectomized animals.
It is thus evident that systemic administration of Triamcinolone to young virgin mice causes mammary stimulation and that this effect only occurs in the presence of the ovary. Morphine induces naloxone-reversible increases of tryptophan and 5-hydroxyindoles in rat cerebral hemispheres, thalamus and cerebellum, but does not do so in striatum, hypothalamus, hippocampus and brain stem.