Acute and chronic effects of intrathecal galanin on behavioural and biochemical markers of spinal motor function in adult rats.

The spinal motor effects of galanin, which co-exists with 5-hydroxytryptamine (5-HT) and thyrotrophin-releasing hormone (TRH) in bulbospinal raphe neurones innervating spinal motoneurones, were examined by administering this neuropeptide through indwelling intrathecal cannulae to conscious adult Wistar rats. The acute effect of intrathecal galanin on spontaneous motor behaviour and the motor behaviours (back muscle contractions and wet-dog shakes) elicited by intrathecal injection of the non-selective 5-HT receptor agonist, 5-methoxy-N, N'-dimethyltryptamine (5-MeODMT) or the TRH analogue, RX 77368 analogue, RX 77368 (pGlu-His-3,3'-dimethyl-ProNH2), respectively, and the chronic effect of galanin on neurochemical markers for bulbospinal raphe neurones and spinal motoneurones were determined. Intrathecal galanin (0.1 to 10 micrograms) did not produce any notable motor behaviours when given alone, but pretreatment with the neuropeptide (0.1 micrograms) significantly attenuated both the number of wet-dog shakes and the amount of forepaw-licking induced by RX 77368, without affecting 5-MeODMT-induced back muscle contractions. Repeated intrathecal galanin administration (1 microgram, twice daily for 5 d) significantly elevated 5-HT (but not 5-hydroxyindoleacetic acid) and substance P-like immunoreactive (LI) levels and choline acetyltransferase (ChAT) activity in the dorsal, but not in the ventral, portion of the thoraco-lumbar spinal cord. In contrast, chronic intrathecal galanin did not alter the TRH- or calcitonin gene-related peptide (CGRP)-LI levels in either spinal cord region.(ABSTRACT TRUNCATED AT 250 WORDS)

Fatal encephalitis caused by Dactylaria constricta var. gallopava in a snowy owl chick (Nyctea scandiaca).

Dactylaria constricta var. gallopava (Cooke) Salkin et Dixon was found to cause fatal encephalitis in a 28-day-old, captivity-bred snowy owl chick (Nyctea scandiaca). The previously healthy bird suddenly developed ataxia, severe torticollis, and extensor rigidity of the legs. Since the animal did not improve with antibiotic or vitamin-mineral supplement therapy, the chick was euthanized 5 days after the onset of neurologic signs. At necropsy, all tissues except the brain were grossly normal. Cultures inoculated with blood from the brain and heart yielded a dematiaceous mould that subsequently proved to be D. constricta var. gallopava. This is the first report of natural central nervous system infection caused by D. constricta var. gallopava in a snowy owl.

In vivo models: evaluating antifungal agents.

A summary is presented on some basic aspects of pure and applied studies involving in vivo antifungal models. A standard mouse model is described for the purpose of establishing acute, systemic fungal infection for drug testing. Three representative mycoses, candidiasis, cryptococcosis, and aspergillosis, and three representative drugs, amphotericin B (Ampho B), 5-fluorocytosine (5-FC) and ketoconazole (KTZ) are given as examples. Second, a quantitative spleen culture technique is described for obtaining quantitative data for the in vivo activity of Ampho B, KTZ and fluconazole in murine histoplasmosis. And finally, special application of the acute infection model will be made to evaluate all four of the above drugs in systemic phaeohyphomycosis with central nervous system involvement.

In vitro and in vivo drug studies with three agents of central nervous system phaeohyphomycosis.

Amphotericin B (Amph B), 5-fluorocytosine (5-FC), ketoconazole (KTZ), fluconazole (FLZ), amorolfine (AMOR) and terbinafine (TER) were tested against 3 agents of central nervous system phaeohyphomycosis in vitro and in life-threatening infections in mice. The fungi studied were Cladosporium bantianum, Dactylaria constricta and Wangiella dermatitidis. The broadest protection against this group of fungi in mice was offered by 5-FC followed by Amph B and FLZ, then KTZ. AMOR and TER were inactive in vivo. The results of in vitro susceptibility testing had no predictive value. In contrast, the data obtained from the mouse models should be useful clinically.

A comparison of bifonazole (BAY H 4502) with clotrimazole in vitro.

The antifungal activity of a new topical imidazole, bifonazole (BAY h 4502, Bayer AG Institute for Chemotherapy), was compared in vitro with that of clotrimazole (BAY b 5097, Schering Corporation) in tests with 67 pathogenic and commensal yeasts, 45 dermatophytes and 14 miscellaneous pathogenic fungi by an agar dilution method. Three media, Kimmig's agar, Sabouraud's agar, and casein-yeast extract-glucose agar were used. Bifonazole was inhibitory for nearly all the yeasts tested including Candida albicans, C. parapsilosis, and Torulopsis glabrata with geometric mean minimal inhibitory concentrations (G-MIC) averaging 5 micrograms ml-1 on all three media. Clotrimazole was the more active drug against these same species with G-MIC's ranging from 0 . 25 to 2 . 10 micrograms ml-1. Results with bifonazole were affected by choice of medium with Kimmig's agar generally giving the lowest MIC's; results with clotrimazole were also affected by choice of medium but to a lesser degree. In nearly all instances, both bifonazole and clotrimazole were inhibitory for the dermatophytic fungi at concentrations of 0 . 50 micrograms ml-1 or less and clotrimazole was the more active drug. Choice of medium was, in general, not a factor with these latter fungi which included Epidermophyton, Trichophyton, and Microsporum species. Both drugs were active against species of Aspergillus (G-MIC's of 3 . 18 micrograms ml-1), Fusarium (G-MIC's ranging from 1 . 59 to 12 . 70 micrograms ml-1) and Scopulariopsis (G-MIC's of 1 . 78 micrograms ml-1); clotrimazole was the more active drug by factors of 2- to 4-fold on all three media. Bifonazole MICs were shown to vary with pH (maximal activity at pH 6 . 5) with selected yeasts when tested on Kimmig's agar. Differences in results obtained with varying inoculum sizes for these same yeasts generally were unremarkable. With selected species of yeasts and dermatophytes, it was determined that the ratio of minimal fungicidal to inhibitory concentrations (MFC/MIC) was much lower for bifonazole than for clotrimazole.