Long-term retention of a peripherally induced flexor reflex alteration in rats

The long-term nature of peripherally induced spinal fixation was examined in the present study. Sixty-three anesthetized rats received 45-90 min of hindlimb stimulation. After a 24-72 h waiting period, the animals were given a midthoracic spinal section and hindlimb asymmetry was assessed. Our results indicate that a compensatory mechanism was activated after stimulation to correct the postural imbalance. Long-lasting effects of stimulation were manifested, however, when the compensatory influence was eliminated by spinal section.     

Chemical Characterization of Ethambutol Binding to Mycobacterium smegmatis

Recent studies showed that critical binding of ethambutol to Mycobacterium smegmatis was both inhibited and reversed by ions. This apparent ion-susceptible characteristic suggested that ethambutol is held at critical sites by electrostatic bonds. Dissociation constant, pH, and ionic strength studies were designed to further characterize ethambutol binding. M. smegmatis was grown in Sauton synthetic liquid medium (pH 7.4) under aerated conditions at 37 C. The pH or ionic strength of the medium was modified to meet the needs of particular experiments. Titration data revealed that ethambutol dihydrochloride has two apparent dissociation constants (pKa(1) = 6.35, pKa(2) = 9.35). Uptake experiments, in which pH was varied, showed that dihydrochloride and free base ethambutol were bound to a greater extent than the monohydrochloride. However, dihydrochloride and free base binding were not related to biological activity. Ethambutol exerted its maximal growth inhibitory effect at pH values near neutrality, where it exists primarily as the monohydrochloride and showed minimal binding. The increased ethambutol binding observed at pH 7.4 in media of lowered ionic strength was consistent with growth studies showing a reduction in the minimal inhibitory growth concentration in such media. However, nonspecific as well as critical binding was enhanced at low ionic strength. We conclude that binding of ethambutol by M. smegmatis involves a heterogeneous group of drug binding sites, only one of which is directly related to biological activity. Although nothing is known about the ethambutol target site itself, critical binding of the drug seems to require the single positively charged monohydrochloride form. Both hydrogen bonds and ionic linkages are probably involved.     

Combined activity of ketoconazole and 5-fluorocytosine on potentially pathogenic yeasts.

In vitro studies based on periodic viable count determinations indicated that the two antifungal drugs ketoconazole and 5-fluorocytosine generally were at least additive in their combined effect on various opportunistic yeast pathogens, including some resistant to 5-fluorocytosine.     

Nonspecific Ionic Inhibition of Ethambutol Binding by Mycobacterium smegmatis

Magnesium sulfate and spermidine were tested for their effects on binding of (14)C-ethambutol by Mycobacterium smegmatis. Concentrations were used that protected the organism from ethambutol inhibition. Sodium salts were examined as possible ethambutol antagonists to test the previously reported specificity of the divalent cation salt effect. Consistent with growth-protection experiments, 20 mM MgSO(4) or 2.0 mM spermidine prevented and reversed (14)C binding by cells shaken with 0.2 mug of (14)C-ethambutol per ml of Sauton medium at 37 C. Sodium salts were not effective ethambutol antagonists when tested at 20 mM, but at concentrations equivalent in ionic strength (mu) to that provided by 20 mM MgSO(4) they were effective. Thus, 20 mM MgSO(4), 80 mM NaCl, or 27 mM Na(2)SO(4) (mu = 0.08) all gave similar results in growth protection and binding experiments, suggesting that MgSO(4) antagonism is a nonspecific ionic effect. Because spermidine (mu 相似文献   

Additional dystrophin fragment in Becker muscular dystrophy may result from proteolytic cleavage at deletion junctions

Becker muscular dystrophy is usually caused by intragenic dystrophin gene deletions that result in production of an internally deleted protein. Previous studies have detected what appears to be a unique dystrophin degradation product that appears only in muscle biopsies from patients with Becker muscular dystrophy. This dystrophin fragment is always seen in addition to the “full-size” dystrophin of the expected size for a given gene deletion. It is only found in biopsies from patients with mutations in the deletion-prone region encompassing exons 45–53, but it does not appear to correlate with any observable phenotype at the clinical level. By correlating the size and locations of dystrophin gene deletions with the size of this degradation product, together with use of region-specific dystrophin antisera, we find that proteolytic cleavage may occur at the deletion breakpoints, perhaps due to alterations of the secondary and/or tertiary structures of the protein. This cleavage results in loss of the carboxy-terminal domains that are thought to be important for interactions between dystrophin and other membrane-bound proteins. © Wiley-Liss, Inc.     

Fungistatic Activity of Miconazole against Candida albicans in Relation to pH and Concentration of Nonprotonated Drug

At less than 10(-5) M, miconazole (MCZ) exerts a fungistatic effect on Candida albicans, presumably by interfering with ergosterol biosynthesis. The imidazole moiety of MCZ is subject to protonation (pKa approximately 6.5). Based on pKa and greater water solubility of protonated (MCZH+) versus nonprotonated (MCZo) drug, fungistatic action ought to be markedly affected by environmental pH, but apparently it is not. In this report growth phase, pH, and concentrations of MCZ and MCZo have been studied in relation to fungistasis. Yeasts were grown in a synthetic liquid medium and MCZ effects were monitored by viability determinations. Results showed that fungistatic activity is little affected by growth phase and is largely independent of drug concentration and pH. Antagonism of fungistasis by low pH was demonstrated only at less than 10(-7) M MCZ. Data supported earlier proposals that MCZo is required for biological activity and suggested that target sites are saturated at very low levels of drug.     

Antagonism of the direct fungicidal action of miconazole by miconazole fungistasis

A weakly fungistatic concentration of miconazole in lag phase yeast cultures ofCandida albicans antagonized development of phenotypic susceptibility to the direct fungicidal action of high-level (i.e. >10^?5 M) miconazole. After development in the absence of drug, maintenance of susceptibility upon continued incubation was also antagonized by low levels of miconazole. This auto-antagonistic effect has important clinical implications.     

Mucocele of the appendix presenting as a sigmoid mass

Mural tumours of the colon are rare and may be difficult to distinguish from extrinsic lesions. We report a case of an apparent intramural sigmoid tumour due to a mucocele of the appendix and discuss the radiological diagnosis of mural tumours of the large bowel.