Penetration and distribution of three lipophilic probes in vitro in human skin focusing on the hair follicle.

Fluorescent model substances of increasing lipophilicity (Oregon Green) 488, Bodipy, FL C5 and Bodipy 564/570 C5) were selected to enable the visualization in the skin using confocal laser scanning microscopy. After measuring the penetration for 18 h, the nonfixed human scalp skin was imaged from the bottom parallel to the stratum corneum and in a cross-section view perpendicular to the skin surface. The images were evaluated by calculating relative accumulation values for different penetrants. The studies indicate that the penetrated amount is highest for Bodipy FL C5 (medium lipophilicity) and lowest for Bodipy 564/570 C5 (high lipophilicity) whereas Bodipy 564/570 C5 (high lipophilicity) reveals the highest relative accumulation in parts of the hair follicle compared to Oregon Green 488 (low lipophilicity). The addition of 30% (v/v) ethanol to the donor phase of substance with a low lipophilicity increases the follicular delivery. From our results we conclude that delivery to the hair follicle can be improved by increasing the drugs lipophilicity and optimizing the composition of the donor phase. However, no conclusion can be drawn about the actual route of transport to the hair follicle.     

Effect of clavulanic acid, sulbactam and tazobactam on three different beta-lactamases from Bacteroides uniformis, Clostridium butyricum and Fusobacterium nucleatum.

The effect of three beta-lactamase inhibitors, clavulanic acid, sulbactam and tazobactam used in clinical practice were compared for their activity against purified beta-lactamases from Bacteroides uniformis, Clostridium butyricum and Fusobacterium nucleatum. The enzymes from B. uniformis and C. butyricum were produced in fermenters under controlled growth conditions and the enzyme from F. nucleatum was produced in batch cultures. Purification of the beta-lactamases was achieved by anion-exchange chromatography, gel filtration and FPLC-technique. The degree of inactivation of beta-lactamase activity was determined spectrophotometrically with nitrocefin as the substrate. The inhibitors in various concentrations were preincubated at 30 degrees C together with the enzyme for different time periods (0.5-120 min) before determination of the remaining beta-lactamase activity. The inhibitors all decreased the activity of the beta-lactamases investigated. Clavulanic acid and sulbactam were capable of reducing the enzyme activity of the B. uniformis beta-lactamase more effectively than the C. butyricum and F. nucleatum beta-lactamases. All beta-lactamases tested were more susceptible to tazobactam than to clavulanic acid and sulbactam.     

Suicide among Swedish dentists. A ten-year follow-up study

In the present study, we have followed a national cohort of dentists, academics, i.e. people with three or more years of post-high school education, and the general population for a period of ten years, and identified all cases of recognized suicide during the period 1961 to 1970. The aim of the study was to assess whether suicide rates are higher among dentists even after adjustment for socioeconomic factors. Results show an elevated standardized mortality ratio (SMR) for male dentists compared to other male academics. Female dentists did not exhibit any increased risk. It is suggested that enhanced interest should be given to the possible etiologic role of not only psychosocial factors but also to psychoorganic consequences of mercury exposure among dentists.     

Inventory of plants used in traditional medicine in Somalia. III. Plants of the families Lauraceae-Papilionaceae.

Thirty-five plants are listed, which are used by traditional healers in the central and southern parts of Somalia. For each species are listed: the botanical name with synonyms, collection number, vernacular name, medicinal use, preparation of remedy and dosage. Results of a literature survey are also reported including medicinal use, substances isolated and pharmacological effects.     

Influence of serotonin on total intravascular capacity in the anaesthetized dog

The influence of serotonin on intravascular volume in the total capacitance circulation has not previously been examined. Thus, blood was drained from the venae cavae to an extracorporeal reservoir and returned to the right atrium at a constant rate so that total intravascular volume changes could be recorded as the inverse of changes in reservoir volume in 31 anaesthetized dogs. Serotonin (588 +/- 47 micrograms) in the left atrium was associated with an initial decrease in intravascular volume of 39 +/- 12 ml (P less than 0.01) followed by an increase of 129 +/- 31 ml (P less than 0.01) above control at 20 min. Mean arterial pressure increased from a control of 74 +/- 4 mmHg to 99 +/- 7 mmHg (P less than 0.01) initially and then decreased to 64 +/- 5 mmHg (P less than 0.05) at 20 min. Following ganglionic blockade with mecamylamine, serotonin caused only a decrease in intravascular volume, which was 73 +/- 12 ml (P less than 0.01) at 20 min. 5-HT2 and alpha-adrenergic blockade with ketanserin did not attenuate the early decrease in intravascular volume. 5-Carboxamidotryptamine (82 +/- 39 micrograms), a 5-HT1 agonist, was associated with only an increase in intravascular volume, which was 82 +/- 13 ml (P less than 0.01) at 20 min and which was abolished after ganglionic blockade. Thus, serotonin causes a biphasic change in total intravascular volume. The initial decrease in intravascular volume is not mediated by a reflex or by 5-HT1, 5-HT2, or alpha-adrenergic receptor stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Appearance and Persistence of Antibodies Against Different Virus Components After Regular Measles Infections

Different measles virus-specific antibody activities in acute, early (11 to 40 days after rash) and late (4 to 20 years postinfection) convalescent sera and gamma globulin were determined. Early immunoglobulin G antibodies gave a poor neutralization, which was increased 10- to 60-fold by addition of anti-gamma globulin.There was a high degree of correlation between titers of hemolysis-inhibiting (HLI) and hemagglutinating-inhibiting (HI) antibodies. However, in one out of fifteen late convalescent sera an HLI antibody titer of 640 in the presence of titer of only 20 in HI tests with Tween 80-either-treated antigen was found. Similar findings were made with sera from two patients with multiple sclerosis included in a parallel study. A somewhat higher titer of HI antibodies was demonstrable in these three sera when untreated material was used as antigen. These findings are interpreted in the following way. Antibodies against the hemagglutinin can block not only virus-specific agglutination but also lysis of red cells. In contrast, antibodies against the hemolysin, besides blocking the biological activity of this component, carry only a slight HI activity. This HI activity can be detected only by use of antigen preparations containing hemagglutinin-associated hemolysin.Complement-fixation (CF) and immunodiffusion tests (the latter were carried out with antigen preparations treated with 0.25% sodium dodecyl sulfate) demonstrated that, in almost all cases, antibodies against nucleocapsid structures dominated quantitatively among antibodies appearing in connection with and persisting after regular measles infections. Generally, only low titers of antibodies reacting with purified small particle hemagglutinin (HA; 10 to 14S) or additional structural or nonstructural components were identified in CF and immunodiffusion tests.     

Exercise but not Prostanoids Enhance Levels of Vascular Endothelial Growth Factor and other Proliferative Agents in Human Skeletal Muscle Interstitium

In the present study we examined whether exercise and prostanoids have an effect on the muscle interstitial concentration of vascular endothelial growth factor (VEGF) and on the proliferative effect of muscle interstitial fluid. Dialysate from resting and exercising human skeletal muscle, obtained either during control conditions or during cyclooxygenase inhibition, was examined for its content of VEGF and for its effect on endothelial cell proliferation. Microdialysis probes with high (960 kDa) and low (5 kDa) molecular-mass cut-off membranes were placed in the vastus lateralis muscle of healthy young males. The subjects performed one-legged knee extensions (20 W). The concentration of VEGF in the 960 kDa dialysate was greater (   P < 0.05  ) during exercise compared to at rest (67 ± 28 vs. 230 ± 22 pg ml⁻¹). The rate of endothelial cell proliferation was 2.7-fold higher (   P < 0.05  ) with the 960 kDa dialysate from resting muscle than with perfusate and was 5.8-fold higher (   P < 0.05  ) than the perfusate value with dialysate from exercising muscle. VEGF was not enhanced with exercise in the 5 kDa dialysate, yet the exercise dialysate induced a 1.9-fold higher (   P < 0.05  ) proliferation than the resting dialysate. Cyclooxygenase inhibition did not affect the VEGF concentration or the proliferating effect of the dialysates (   P > 0.05  ). This study demonstrates for the first time that VEGF is present in the interstitium of human skeletal muscle and that exercise enhances the interstitial concentration of VEGF and of other, as yet unidentified, angiogenic compounds. Products of cyclooxygenase do not appear to have an effect on the release of VEGF or other proliferative agents in human skeletal muscle.