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Five preparations of ointment containing aminosidine were used to treat lesions of 'Old World' cutaneous leishmaniasis. A preparation containing 12-15% aminosidine with 10% urea in white soft paraffin was nontoxic. 23 of 27 patients treated healed in a mean of 6.7 weeks, the ointment being applied daily for up to 12 weeks.
Sodium stibogluconate is the mainstay of treatment for all forms of leishmaniasis. Therapy is associated with an increase in serum aminotransferases. In this study liver damage was assessed during treatment of American cutaneous leishmaniasis with sodium stibogluconate and also in a control group given aminosidine. In addition to standard liver function tests, acute hepatocellular damage was assessed by measuring plasma glutathione S-transferase B1 (GST), and hepatic metabolic capacity was assessed by a caffeine clearance (CCL) test, before, during and after treatment. Thirteen patients were treated; 5 received sodium stibogluconate, 6 received aminosidine and a further 2 patients received aminosidine followed by sodium stibogluconate. Treatment with sodium stibogluconate was associated with an increase in both alanine aminotransferase (ALT) and GST and a fall in the CCL, indicating both hepatocellular damage and functional impairment. Six weeks after treatment had stopped ALT and GST had returned to pre-treatment levels and the CCL remained depressed in only one patient. Patients given aminosidine did not show any evidence of liver damage. Sodium stibogluconate is associated with significant hepatocellular damage and hepatic functional impairment. However, this is rapidly reversible on drug withdrawal. We suggest that liver function is monitored throughout treatment and that patients with pre-existing liver disease receive alternative treatment.
Fifty-two patients with American cutaneous leishmaniasis (ACL) from the Pacific coast of Ecuador were treated topically with an ointment containing 15% paramomycin (PR) and 12% methylbenzethonium chloride (MBCL) in vaselinum album (white soft paraffin; white petrolatum). After 20 applications (over 10 or 20 d) all lesions showed complete epithelialization within the first 100 d. Five patients developed new lesions during the one year observation period; 2 of these were probably reinfections. Considering all 5 cases as treatment failures, the healing rates were: 72% after 50 d, 90% after 100 d, and 85% after 360 d. In a separate study in the same area, a group of 23 patients was left without treatment for 3 months. Only 9% of the untreated patients healed spontaneously after 50 d. Growth of the lesion, inflammation and pain were observed at the beginning of treatment. After treatment, most lesions healed rapidly without scars. The drug was well accepted by the patients and was easy to administer under tropical field conditions.
This randomized, open sequential design trial was set up to assess the efficacy, tolerability and toxicity of 20 d courses of combined intramuscular aminosidine and sodium stibogluconate at various dosages in patients with newly-diagnosed kala-azar in Bihar, India. Three successive studies of 96 patients each were originally planned with aminosidine administered at 12, 6 and 3 mg/kg/d, respectively. For each aminosidine dosage, patients were randomly assigned to receive sodium stibogluconate at 20, 10 or 5 mg/kg/d of antimony. Ninety-six patients were enrolled and assigned aminosidine 12 mg/kg/d as scheduled. In the subsequent study with aminosidine at 6 mg/kg/d, the trial was interrupted after 40 patients had entered owing to inadequacy of the treatment. With aminosidine 12 mg/kg/d the success rates with sodium stibogluconate at 20, 10 and 5 mg/kg/d were 88%, 71% and 72%, respectively and did not differ significantly. With aminosidine 6 mg/kg/d, 69%, 50% and 46% of patients were cured with the same sodium stibogluconate doses, respectively; again, there was no significant difference between the subgroups. The overall success rate with aminosidine at 12 mg/kg/d (76%) was significantly higher than that with 6 mg/kg/d (55%) (odds ratio = 2.69; 95% confidence interval, 1.11-6.4). Patients improved clinically and the treatments were equally well tolerated. The combination of aminosidine 12 mg/kg/d and sodium stibogluconate 20 mg/kg/d for 20 d appears to be an effective and safe replacement in Bihar for sodium stibogluconate alone for > or = 40 d.
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Previous work from our laboratory has demonstrated that a subclass of the aminoglycoside antibiotics, those containing the drug fragment paromamine, stimulates mistranslation in cell-free protein-synthesizing systems derived from eucaryotic cells. We report here experiments which show that the ciliate Tetrahymena thermophila (formerly T. pyriformis, syngen 1) is sensitive to the paromamine-containing aminoglycoside antibiotics. The drugs are active with respect to growth inhibition, inhibition of protein synthesis in the whole organism, inhibition of protein synthesis in vitro and the stimulation of mistranslation in cell-free protein-synthesizing systems. Because of their misreading properties, these drugs may be useful in isolating and propagating strains carrying mutations which can be translationally suppressed (that is, missense and nonsense mutations).
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We have studied the promoter of the gene encoding aminoglycoside acetyltransferase (aacC9) in neomycin-producing Micromonospora chalcea. S1 nuclease mapping showed that the transcription initiation point of this gene is at the translation start point, with no evidence of a conventional ribosome-binding site. The aac of paromycin-producing Streptomyces rimosus forma paromomycinus shows the same characteristic; there is no homology in the promoter regions of the two genes, whereas the coding sequences are very similar.
The specific binding of aminoglycoside antibiotics to the bacterial ribosomal decoding site (A-site) has inspired the study of RNA-small molecules interactions and the search for novel RNA binders. Among the numerous RNA targets studied so far, the A-site holds a unique place. It is among the few truly validated RNA targets for which naturally occurring ligands have been discovered as "cognate" binders. In addition, due to its encapsulating architecture, the A-site is a more discriminating RNA target when compared to other RNA sequences. Previous observations and current challenges for the designers of potent and specific RNA binders are discussed.
RNA recognition by natural aminoglycoside antibiotics depends on the 2-deoxystreptamine (2-DOS) scaffold which participates in specific hydrogen bonds with the ribosomal decoding-site target. Three-dimensional structure information has been used for the design of azepane-monoglycosides, building blocks for novel antibiotics in which 2-DOS is replaced by a heterocyclic scaffold. Azepane-glycosides showed target binding and translation inhibition in the low micromolar range and inhibited growth of Staphylococcus aureus, including aminoglycoside-resistant strains.
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E-cadherin and catenins play key roles in cell adhesion and motility. Little is known about the changes in expression of these molecules in the progression of ovarian carcinomas. In the present study, the immunohistochemical expression of E-cadherin and alpha-, beta-, and gamma-catenins was examined in 77 cases of ovarian carcinoma. In addition, the expression of these molecules was evaluated in 26 matched pairs of primary and metastatic lesions of advanced ovarian carcinomas. Of the 77 primary lesions, positive staining for E-cadherin and alpha-, beta-, and gamma-catenin was observed in 75 (97%), 63 (82%), 71 (92%) and 57 (74%) cases, respectively. Positivity for E-cadherin and alpha-, beta-, and gamma-catenin was significantly decreased in stage III and IV tumors compared with stage I and II tumors, suggesting that expression of the cadherin-catenin complex is reduced with the advancing stages of a tumor. Interestingly, expression of E-cadherin and alpha-, beta-, and gamma-catenin in the lesions of peritoneal dissemination was significantly increased compared with the primary lesions. These findings suggest that expression of the cadherin-catenin complex changes markedly and that reexpression may occur during the peritoneal dissemination of ovarian carcinoma cells.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.