Antifungal therapy of dermatophytosis in guinea pigs and congenitally athymic rats

Guinea pigs and athymic nude (RNU/RNU) rats were used to assess the efficacy of three orally administered antifungal agents — Tolciclate, Tolnaftate, and Ketoconazole — against Trichophyton mentagrophytes dermatophytosis. All three antifungal agents inhibited the test strain of T. mentagrophytes in vitro. Antifungal agents were tested in intervention (oral therapy started 5 days after challenge) or prophylaxis (oral therapy started 5 days before challenge) protocols. Oral treatment of dermatophytosis on guinea pig skin demonstrated that Tolciclate and Tolnaftate alleviated clinical symptoms and shortened the duration of the dermatophytosis, in comparison to nontreated controls. Assessment of antifungal efficacy in the guinea pig model was time consuming (30–35 days) and variability in the duration and severity of clinical symptoms on guinea pig skin was common.Oral therapy of chronically infected athymic rats demonstrated that Tolciclate, Tolnaftate, and Ketoconazole were effective antifungal agents in vivo. Obvious improvement in clinical symptoms of dermatophytosis (i.e. less erythema and fewer lesions) was evident with all three antifungal agents within 10 days of starting oral therapy. By day 20, athymic rats that were treated with either Tolciclate or Ketoconazole showed marked clinical improvement of the chronic dermatophytosis.Chronically infected athymic rats, which lack thymus matured T-cells, are a promising new model to evaluate the efficacy of antifungal agents by culture, histology, and visual observations of clinical symptoms.     

The use of catheter-tipped pressure transducers for chronic measurement of genital tract pressures in the ewe. I. Implantation technique, catheter performance and data analysis

A computerised system for chronic in vivo monitoring of genital tract pressure in the ewe is described. Solid-state, catheter-tipped pressure transducers were surgically implanted in the uterine tube (ampulla), ipsilateral uterine horn and abdomen of five non-pregnant parous ewes. The catheters were connected to a portable computer which recorded the pressure at each location once per second and was programmed to analyse the data as mean pressure and area under the contraction curve over given periods. The catheters remained implanted for up to 129 days and 252 daily recordings were made. Analysis of spontaneous activity showed little variation in mean pressure of work done over four successive ten-minute periods. Although the amplitude of uterine contractions varied quite dramatically, chiefly in relation to variation in the plasma progesterone concentration, ampullary activity was unaffected by such changes. Genital tract pressures did not appear to be influenced by abdominal events. The catheters provoked minimal tissue reaction, and it is suggested that the system is suitable for chronic in vivo recording of genital tract pressure in the ewe.     

Reduction in headache patients' medical expenses associated with biofeedback and relaxation treatments

Comparisons are made of self-reported medical costs from a sample of headache patients who underwent various combinations of relaxation training and biofeedback training. The average costs for the 2 years prior to self-regulatory treatment were $955±480 (3 SEM) for 45 patients; for the 2 years after completing treatment the average costs were $52±28 (3 SEM) for patients. Within the limitations of the study, medical costs do seem to have been markedly reduced.This research was supported by a grant from NINCDS, NS-15235.     

Effect of indomethacin on proteinuria in rats with autologous immune complex nephropathy

Although non-steroidal anti-inflammatory agents have been used to reduce levels of urinary protein excretion in patients with the nephrotic syndrome, the general usefulness of these drugs in proteinuric states remains unclear. The present study was designed to confirm the efficacy and to investigate some of the mechanism/s of action of non-steroidal anti-inflammatory agents in animals with proteinuria as the result of a single form experimental renal disease. Autologous immune complex nephropathy was produced in groups of Lewis rats by the administration of autologous tubular F×1A antigen. After marked proteinuria developed, indomethacin (8 mg/kg/day) was administered orally to one group of animals for five days while a control group received only vehicle. The level of urinary protein excretion in the indomethacin treated animals was 420 ± 198 mg/day compared to a level of 1180 ± 306 seen in the untreated animals (p < 0.05). When the indomethacin-treated and control animals were compared, the reduction in proteinuria could not be found to be associated with a change in the glomerular filtration rate, urine electrolyte or osmolar excretion rates, electron microscopic appearance of the glomerular basement membrane, or a change in the glomerular permeability to neutral dextran. Treatment of animals with either sodium salicylate or lower doses of indomethacin (both of which resulted also in significant falls in urinary prostaglandin E excretion rates) failed to reduce the levels of proteinuria. Thus, indomethacin was capable of reducing the levels of protein excretion in rats with autologous immune complex nephropathy although the mechanism of action of this agent remains unclear.     

Effects of phorbol myristate acetate,phorbol dibutyrate,ethanol, dimethylsulfoxide,phenol, and seven metabolities of phenol on metabolic cooperation between chinese hamster v79 lung fibroblasts

The effect of phorbol myristate acetate, phorbol dibutyrate, ethanol, dimethylsulfoxide, phenol, and seven metabolites of phenol on metabolic cooperation were assessed as a function of mutant cell recovery from populations of cocultivated hypoxanthine-guanine phosphoribosyl transferase-deficient mutant (HGPRT–) and wild-type (HGPRT+) Chinese hamster V79 lung fibroblasts. Phorbol myristate acetate and phorbol diputyrate, two established tumor promoters, were potent inhibitors of metabolic cooperation. Ethanol and dimethylsulfoxide, solvents commonly used to prepare chemicals for testing, weakly inhibited metabolic cooperation. Phenol and phenylglucuronide had no effect on metabolic cooperation. Four oxidative metabolites (1,4-benzoquinone, catechol, hydroxyquinol and quinol) inhibited metabolic cooperation. Phenylsulfate weakly inhibited metabolic cooperation. Conversely, 2-methoxyphenol, a methylated derivative of catechol, appeared to enhance metabolic cooperation. These results generallyAbbreviations CAS Chemical Abstracts Service - DMSO dimethylsulfoxide - ETOH ethanol - HGPRT hypoxanthine-guanine phosphoribosyl transferase - HGPRT+ HGPRT-competent - HGPRT– HGPRT-te]deficient - MC metabolic cooperation - MC+ metabolic cooperation-competent - MC– metabolic cooperation-deficient - MEM minimum essential medium - PDBu phorbol dibutyrate - PMA phorbol myristate acetate - 6TG 6-thioguanine - 6TG^r 6-thioguanine-resistant - 6TG^s 6-thioguanine-sensitive - V79/MC assay Chinese hamster V79 lung fibroblast assay for metabolic cooperation     

Foliar flavonoid aglycones of Phoebanthus

The diploid Phoebanthus tenuifolius and the tetraploid P. grandiflorus yielded identical complements of foliar flavonoid aglycones, including the compounds nepetin, jaceosidin, and hymenoxin. Flavonoid data do not resolve the origin of the tetraploid species. The similarity between the flavonoids of Phoebanthus and those earlier reported for Helianthus would support a merger of the two genera.     

Neuroendocrine and behavioral effects of m-chlorophenylpiperazine administration in rhesus monkeys

The effects of m-chlorophenylpiperazine (mCPP), a serotonin receptor agonist, on the release of plasma prolactin (PRL), growth hormone (GH), and cortisol in the rhesus monkey were studied. mCPP was administered intravenously at doses of 0.5, 1.5, and 3.0 mg/kg. GH and cortisol were increased significantly at all doses whike PRL was significantly increased only following administration of 3.0 mg/kg mCPP. mCPP administration also produced behavioral alterations in each monkey, including sedation, penile erection, and defecation. PRL, GH and behavioral responses to mCPP were completely blocked by pretreatment with the serotonin anatgonist metergoline (MTG). However, pretreatment with MTG failed to entirely antagonize the cortisol response to mCPP. These data suggest that mCPP has prominent neuroendocrine and behavioral effects which are mediated, in part, by serotonergic mechanisms.     

Dietary ascorbic acid deficiency in guinea pigs: No effect on ethanol preference,spiroperidol binding,or monoamine oxidase activity

Ascorbic acid levels are commonly reported to be decreased in alcoholics. Although this deficiency could be due to dietary factors, there is evidence that ascorbic acid may be involved in the metabolism and acute effects of ethanol, possibly related to the pathogenesis of alcoholism. Therefore, we examined ethanol preference in guinea pigs receiving an ascorbate deficient $\text{vs}$ a normal diet. Brain and spleen ascorbic acid levels were dramatically decreased, but ethanol preference was not altered by the acute dietary deficiency of this vitamin. In addition, an acute stressor (cold water swim), alone or in combination with ascorbate deficiency, had no effect on ethanol preference. At termination of the experiment, two measures of brain aminergic function (MAO activity and ³H-spiroperidol binding), purportedly altered by ethanol or ascorbic acid or both, were not associated with tissue ascorbate levels.     

Cytokinin-induced switch in development in excised cotyledons of radiata pine cultured in vitro

Cotyledons of Pinus radiata D. Don were cultured under shoot-forming (plus cytokinin) and elongating (minus cytokinin) conditions. Using. autoradiographic and precursor incorporation techniques, the sites and rate of macromolecular synthesis were examined during the first five days in culture. Active incorporation of ³H-thymidine, ³ H-uridine and ³H-leucine occurred. In shoot-forming cotyledons the incorporation became preferentially located in the epidermal and sub-epidermal cell layers in contact with the medium. In elongating cotyledons, in contrast, incorporation was randomly distributed, and the amount of incorporation declined with time. Biochemically, differences in DNA, RNA and total protein synthetic patterns were observed. In elongating cotyledons the rates of RNA and protein synthesis were higher during the first 48 h than in shoot-forming tissues, after which the synthetic rates were similar. Two peaks of newly formed DNA were observed in both tissues. These findings indicate that the cytokinin-induced changes in developmental pathways began within 24 h in culture.