Role of the pituitary in cyproheptadine-induced pancreatic beta-cell toxicity

Summary Hypophysectomized rats given cyproheptadine (40 mg/kg) for 10 days exhibited a loss of pancreatic immunoreactive insulin and ultrastructural changes in the cytoplasm of beta-cells. Sham-operated animals given cyproheptadine showed identical changes in pancreatic beta-cells except that cytoplasmic involvement progressed to the formation of large vacuoles. The pituitary is not directly involved with the cyproheptadine-induced depletion of pancreatic insulin but plays a role in the formation of large cytoplasmic vacuoles.Acknowledgments. This work was supported by U. S. Public Health Service, grant GM 12675.     

Continuous registration of the pancreatic blood flow after intravenous application of glucose

Zusammenfassung Die Hyperglykämie nach einmaliger stossartiger Glukoseinjektion bewirkt einen Durchblutungsanstieg der Bauchspeicheldrüse. Dieser wurde kontinuierlich mit einem elektromagnetischen Blutstrommesser bei narkotisierten Hunden registriet. Der Anstieg setzt sich aus 2 Abschnitten zusammen, wovon der erste unspezifisch auch in der A. femoralis auftritt.     

Inhibition de la cancérogenèse spontanée chez les souris R III et AkR par des implants de tissus cancéreux modifiés

Summary (1) After a 24-h passage in a rabbit, fragments of spontaneous isologous mammary carcinoma were implanted under the skin of young R III females. This procedure was found to prevent the appearance of spontaneous mammary tumours in a high percentage of these animals. The subsequent appearance of carcinoma was to be observed in only 23% of treated animals as compared with 51% in controls.(2) After a 24-h passage in a rabbit, fragments of leukotic isologous tissue, implanted subcutaneously in young AkR females, reduced subsequent spontaneous leukomogenesis from 85 to 38%.     

Über die hemmung des wachstums vonLactobacillus casei durch einige antiphlogistica

Summary A new method for the classification of antiphlogistics is described using the growth inhibition ofLactobacillus casei. In this test the fenamic acids and particularly the new class of the Cinnopentazon-antiphologistics (Scha 306, Scha 764 etc.) exhibit bacteriostatic properties of a medium intensity.

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Alexander von Muralt zum 65. Geburtstag gewidmet.     

Recombination: Multiply infected spleen cells in HIV patients

The genome of the human immunodeficiency virus is highly prone to recombination, although it is not obvious whether recombinants arise infrequently or whether they are constantly being spawned but escape identification because of the massive and rapid turnover of virus particles. Here we use fluorescence in situ hybridization to estimate the number of proviruses harboured by individual splenocytes from two HIV patients, and determine the extent of recombination by sequencing amplified DNA from these cells. We find an average of three or four proviruses per cell and evidence for huge numbers of recombinants and extensive genetic variation. Although this creates problems for phylogenetic analyses, which ignore recombination effects, the intracellular variation may help to broaden immune recognition.     

Sulindac sulfide suppresses 5-lipoxygenase at clinically relevant concentrations

Sulindac is a non-selective inhibitor of cyclooxygenases (COX) used to treat inflammation and pain. Additionally, non-COX targets may account for the drug’s chemo-preventive efficacy against colorectal cancer and reduced gastrointestinal toxicity. Here, we demonstrate that the pharmacologically active metabolite of sulindac, sulindac sulfide (SSi), targets 5-lipoxygenase (5-LO), the key enzyme in the biosynthesis of proinflammatory leukotrienes (LTs). SSi inhibited 5-LO in ionophore A23187- and LPS/fMLP-stimulated human polymorphonuclear leukocytes (IC₅₀ ≈ 8–10 μM). Importantly, SSi efficiently suppressed 5-LO in human whole blood at clinically relevant plasma levels (IC₅₀ = 18.7 μM). SSi was 5-LO-selective as no inhibition of related lipoxygenases (12-LO, 15-LO) was observed. The sulindac prodrug and the other metabolite, sulindac sulfone (SSo), failed to inhibit 5-LO. Mechanistic analysis demonstrated that SSi directly suppresses 5-LO with an IC₅₀ of 20 μM. Together, these findings may provide a novel molecular basis to explain the COX-independent pharmacological effects of sulindac under therapy.     

Effects of the psychodysleptic drug psilocybin on visual perception. Changes in brightness preference

Zusammenfassung Die in gesunden, jungen Volontären durch Psilocybin hervorgerufene, reversible Veränderung der bevorzugten Helligkeit kann mit der Stabilität der Wahrnehmungspersönlichkeitsstruktur, nicht aber mit der mydriatischen Wirkung der Droge in Beziehung gebracht werden.