Is the excretion of sebum regulated?

The kinetics of sebum excretion on the forehead of volunteers were measured over a period of at least 7 h. The transmission data obtained by the ground glass method were transformed into weight (sebum/cm2). The excretion time function can be described by the equation: w = A . (1 - B . e -C.t). This nonlinear function is typical for modes of excretion in the biological field. Regulation of sebum excretion is probable. Objections against such regulation by feedback were discussed.

Effects of skin extract on sebaceous gland function in the rat.

The subcutaneous injection of a rat skin extract inhibits sebum excretion. The mitotic rate in the sebaceous glands is reduced. Therefore, a chalone of the sebaceous gland seems to exist. The regulation of sebum excretion is discussed.

Comparative studies on the circadian rhythm of corticosterone, lipid and cholesterol levels in adrenals and blood of rats.

The time-dependent relationship of corticosterone, lipids and cholesterol over a 48-hr period was studied in the adrenals and blood of rats. In addition an attempt was made to determine whether there was a reciprocal dependence among these compounds and also a correlation between corticosterone and cholesterol in the adrenals and blood. Corticosterone and cholesterol exhibit a circadian rhythm in the adrenals and blood. The same is true for lipids in the serum. A reciprocal dependence between the compounds in the adrenals and blood could not be demonstrated. Only the time-dependent processes of the corticosterone content in the adrenals and plasma are well correlated with each other. High levels of these steroids in the adrenals are associated with high levels of these steroids in the plasma and vice versa. An inverse correlation between corticosterone and cholesterol exists in the adrenals and in blood. Maximal levels of corticosterone correspond to minimal levels of cholesterol and vice versa.

Autoradiographic studies of the diurnal rhythm of the cell proliferation in the adrenal cortex of the rat.

With the aid of the autoradiographic technique we examined the question of diurnal or circadian rhythm of the cell proliferation as well as the mitotic rate in the three zones of the adrenal cortex of the rat. To evaluate the diurnal rhythm it is necessary to run experiments within 24-hour intervals. In order to examine observed variations as to their reproducibility we prolonged our investigations over a period of 72 hours. The proliferation activity as well as the mitotic rate in the zona glomerulosa show no diurnal rhythm. This is not so in the zona fasciculata. Here we find a correlated circadian rhythm for both parameters.

Influence of heart rate on systolic time intervals: effects of atrial pacing versus dynamic exercise.

The effects of atrial pacing and dynamic exercise in the supine position on systolic time intervals (STI) were compared in 10 normals. In another group of 13 normals, the effect of exercise alone on STI was tested. A linear shortening of electromechanical systole (QS2) and left ventricular ejection time (LVET) with increasing heart rate was demonstrated with right atrial pacing and dynamic exercise in the frequency range between 60 and 140 beats/min. However, the shortening of LVET was significantly less (p less than 0.01) with exercise compared to pacing. This is explained by an increase in left ventricular stroke volume with exercise. The preejection period (PEP) was significantly (p less than 0.001) shortened with exercise, but there was no change with atrial pacing. Thus, changes in heart rate (HR) alone, without changes in the dynamic state of the heart, did not influence PEP. It is suggested that PEP at rest should not be corrected for heart rate. The supine exercise regression equations for correction of heart rate for LVET and PEP differ from both the resting and the upright exercise regression equations. With exercise a frequency correction of STI using regression equations should be abandoned. Instead, uncorrected STI at standard heart rates (e.g., 100, 110, and 130 beats/min) should be taken for comparison. Heart rate standardization should be employed using the formula: Formula (See Text).

Diagnostic problems in upper gastrointestinal bleeding.

In this editorial problems of different diagnostic procedures, the time of endoscopy, i.e. emergency endoscopy procedures, and its complications, are discussed. Criteria for a risk patient and possibilities of endoscopic therapy or operation are discussed.

Comparative cardiac toxicity of the i.v. administered benzimidazole pyridazinon derivative Pimobendan and its enantiomers in female Beagle dogs.

The new positive-inotropic and vasodilatating drug Pimobendan (racemate), 4,5-dihydro-6-[2-(4-methoxyphenyl)-1H-benzimidazole-5-yl]-5-methyl-3 (2-H)-pyridazinone, and its enantiomers were investigated with regard to their cardiotoxicity in young adult female Chbb: Beagle dogs. The racemate and the (-)-isomer (eutomer) were intravenously injected once daily for 4 consecutive weeks at doses of 0.25, 0.75 and 2.25 mg/kg, and the (+)-isomer (distomer) at doses of 0.75, 2.25 and 6.75 mg/kg, respectively. Clinical signs, hematological, clinico-chemical, ophthalmologic and electrophysiological parameters were monitored. Plasma concentration-time profiles of the parent compound and the major metabolite UD-CG 212 were established on day 1 and in week 4 using an HPLC assay. Partial areas under the curves from 0.08 h to 1 h (AUC0.08-1 h) as well as the plasma concentration at time point 0.5 h/C0.5 h) were used for statistical calculations. Necropsy and histopathologic examination were performed after completion of the treatment period. Reduction of the blood pressure occurred already at low dosages of the racemate and the eutomer, but only in high dose distomer-treated animals. A tendency to tachycardia developed only in high dose females receiving the racemate. Consequently, with respect to the pharmacological effects and the adverse events, the racemate is equivalent to the eutomer. Plasma concentrations of parent compound and metabolite were dose-linear for racemate, eutomer and distomer within the dose range 0.25-2.25 mg/kg.d at both time points. There were no significant effects of form or repeated administration. A moderate increase of AUC0.08 1 h and C0.5 h could be seen on day 23 for the distomer indicating a stereoselektive metabolism of the latter. Histologic changes of the valvular and parietal endocardium being termed jet lesion were observed after administration of the racemate (> or = 0.75 mg/kg.d) and the eutomer (> or = 0.25 mg/kg.d) at distinctly lower doses than after the distomer (> or = 2.25 mg/kg.d). Furthermore, extent and severity of the morphologic lesions were found to be higher in dogs exposed to the racemate or the eutomer than in those receiving the distomer. The results gave evidence that the so-called cardiotoxicity by Pimobendan in dogs resulted from the exaggerated pharmacodynamic effect but not from the chemical nature of the compound per se. They corroborate also the previously raised assumption that the exaggerated pharmacodynamic activity of cardiotonic compounds in the broadest sense accounts for their morphologic adverse effects in experimental animals.

The Himalayan rabbit (Oryctolagus cuniculus L.): spontaneous incidences of endpoints from prenatal developmental toxicity studies.

The historical database represents the spontaneous, i.e. normal changes of characters, in laboratory animals, and is a must for the assessment of toxic effects of compounds. For the Himalayan rabbit (CHBB:HM, SPF) background data were collected from the control groups of regulatory studies between 1968-1999 in the Biberach laboratory of Boehringer Ingelheim (Germany). In the present study these data were compared with the background data from the years 1974-1984, with those from the Ingelheim laboratory, Germany (1977-1984) and those from the breeding colony at Kawanishi, Japan (1971-1991, 1972-1984). Fertility in the Biberach laboratory was relatively constant through the years, due to the strict breeding system. Litter parameters (corpora lutea, implantations and viable fetuses), including fetal sex distribution and fetal weight, were constant in the Biberach laboratory through the years and compared well with the data from Ingelheim and Kawanishi. From these three laboratories the results of spontaneous changes in fetal morphology above 0.1% incidence suggest a pattern of deviations from the Bauplan (fundamental body plan). These comprise synosteosis of sternebrae, lumbar (additional) ribs, hypoplasia of 12th rib, status of ossification, aplasia of gall bladder, hypoplasia of gall bladder, incompletely subdivided lung, dilated ventricle of heart, deviations at the A. carotis and at the aortic arch and flexure of paw. The absence of a time-dependent statistical trend indicates that the spontaneous change of endpoints remained constant through the time axis. Comparison with the spontaneously changed fetal morphology of the other strains (NZW, JW, SF rabbits) does not provide support for their being a totally strain-specific pattern, and this pattern may be closer to the species than specific to a single strain. The firm patterns of deviations in fetal morphology provide suitable and valuable markers for assessing toxic effects on ontogenesis. According to our experience these morphological endpoints react very sensitively to teratogenic compounds, which is demonstrated by increased incidences. Our knowledge of evolution of organisms and of mechanisms leading to morphological deviations points to a strict selection of phenotypes. For laboratory animals the decisive selection factors are defined by man. These are nutritive factors, environmental conditions, the mating system, handling and treatment, and experimental design. All these factors have to be held constant through the years, which is an absolute pre-condition for the application of valid historical data. The Himalayan rabbit is highly suitable for use in developmental toxicity studies due to the stability of reproductive data within the same laboratory over a period of more than 30 years, due to the similarity of reproductive data among three different laboratories, and due to an absence of relevant differences to the reproductive data of other rabbit strains.

[Effects of a new beta-blocker (CI 775) on left ventricular hemodynamics at rest and during exercise (author's transl)]. / Die Wirkung des neuen Beta-Rezeptorenblockers Bevantolol (CI 775) auf die linksventrikuläre Ruhe- und Belastungshämodynamik.

The effects of a new beta-blocking agent (CI 778) were studied in 8 patients in whom non-invasive data suggested absence of significant organic heart disease. The left ventricular hemodynamics at rest and during bicycle exercise were measured before and after intravenous administration of 0,9 mg/kg body weight. With exercise there was a significantly smaller increment of heart rate (18%) after beta-blockade. Stroke volume index at rest was significantly lower (17%) after administration of CI 775; the difference disappeared with exercise. There was an 18% decrease of the resting cardiac output after CI 775 and a 23% decrease with exercise. Significant changes at rest and with exercise indicating a negative inotropic action of CI 775 were noted for max dP/dt and peak measured velocity of circumferential fiber shortening (Vpm). The left ventricular enddiastolic pressure with exercise increased with borderline significance by 41% after CI 775. Also left ventricular stroke work index at rest and with exercise decreased moderately (n.s.), the systemic arterial resistance changed to the same extent as cardiac output decreased. Also the arterial venous oxygen difference increased after CI 775 only according to the decrease of cardiac output. The data suggest the hemodynamic properties of CI 775 are located between propranolol and practolol within the spectrum of available beta-blockers.

The influence of castration on cell proliferation in the adrenal cortex of female rats.

Proliferation kinetics in the zones of the adrenal cortex of female rats after castration are reported. Following ovariectomy a wave of increased cell proliferation was observed in the zona glomerulosa and zona fasciculata after 1 and 2 days respectively. Increased cell proliferation in the zona reticularis was only slight. Cell proliferation returned to the level in control animals at 4 weeks. It is assumed that the regulative process following ovariectomy takes place directly in the adrenal cortex but it is possible that steroid metabolism in the liver is of importance. No relationship between the 3H-TdR labelling index (LI) and the mitotic index (MI) was observed.