A perspective on cirrhotic cardiomyopathy.

Cardiac dysfunction in patients with cirrhosis and potential clinical implications have long been known, but the pathophysiology and potential targets for therapeutic intervention are still under investigation and are only now becoming understood. The pathophysiological changes result in systolic dysfunction, diastolic dysfunction, and electrophysiological changes. Here, we aim to review cirrhotic cardiomyopathy from a cellular and physiological model and how these patients develop overt heart failure in the setting of stress, such as infection, ascites, and procedures including transjugular intrahepatic portosystemic shunt, portocaval shunts, and orthotopic liver transplantation. We will also review the most current, although limited, available therapeutic modalities.

Reversible cardiomyopathies--a review.

End-stage renal disease, cirrhosis, obesity, tachycardia, and extreme stress have all been shown to result in impaired left ventricular function. It is becoming clear, however, that the cardiomyopathies associated with these states are reversible after resolution of the underlying process. In this article, we present the current data demonstrating that renal transplantation, liver transplantation, and bariatric surgery can lead to reversal of uremic, cirrhotic, and obesity cardiomyopathies, respectively. We also discuss the reversibility of tachycardia-induced cardiomyopathy after radiofrequency ablation or pharmacologic therapy for rate or rhythm control and the reversibility of stress-induced cardiomyopathy with supportive care.

A novel macrolactam-disaccharide antifungal antibiotic. Taxonomy, fermentation, isolation, physico-chemical properties, structure elucidation and biological activity.

A novel natural product (1), with antifungal activity was isolated from the culture broth of an actinomadurae. The active compound was separated from broth by n-butanol extraction and purified by silica gel and multicoil counter current chromatography. Physico-chemical data suggested the structure of this compound to be a novel macrolactam disaccharide related to Sch 38518 (3). The structure was determined by spectroscopic studies on the acetate derivative. It was active against Candida spp. (MIC's, 4 approximately 64 micrograms/ml) but less than the monosaccharide, Sch 38518 (MIC's, 1 approximately 16 micrograms/ml).

Biotransformation of sisomicin to gentamicin C2b.

Sisomicin was transformed to gentamicin C(2b) by Micromonospora rhodorangea NRRL 5326. The mechanisms involved in the biotransformation are the 6'-N-methylation and the (4'-5')-reduction. The progression of the methylation was followed by the isotope technique, but the reduction reaction was not monitored.

Formation of methylated and phosphorylated metabolites during the fermentation process of verdamicin.

In an attempt to understand the biosynthetic processes leading to the formation of verdamicin (end product), we have examined the patterns of the formation of methylated and phosphorylated metabolites, which resulted from either the addition of l-[methyl-(14)C]methionine or [(32)P]KH(2)PO(4) to the fermentation. Incorporation of label from l-[methyl-(14)C]methionine into the bioactive sisomicin, verdamicin, and the chromatographically polar components increased with the progression of time. Two methylated bioinactive metabolites were found in the culture broth after removal of the methylated bioactive metabolites. In contrast to the bioactive metabolites, incorporation of the methyl-(14)C label into the two methylated bioinactive metabolites decreased with the progression of time. A phosphorylated bioinactive metabolite (nonmethylated) was also found in the culture broth, fermented in the presence of [(32)P]KH(2)PO(4). The role of the phosphorylated metabolite in the biosynthesis of the bioactive metabolites cannot yet be explained.

Micromonospora-produced sisomicin components.

A sisomicin fermentation carried out in the presence of (methyl-14C)-L-methionine resulted in a crude mixture, composed of methyl-14C-labeled sisomicin as a major component; and two 4''-C-desmethylsisomicin (66-40B and 66-40D) isomer-like components, an unidentified component and a gentamicin A-like antibiotic as minor components. When (methyl-14C)-L-methionine was added in an early stage of the fermentation (24 hours), incorporation of methyl-14C-label into polar components (e.g., gentamicin A-like antibiotic) preceded that into sisomicin. Chromatographic evidence for the bioconversion of (methyl-14C)-gentamicin A to a radioactive sisomicin-like product (possibly (3''-N-methyl-14C)-sisomicin) was seen, when a Micromonospora blocked mutant was incubated in the presence of the former antibiotic.

A new broad spectrum aminoglycoside antibiotic, G-52, produced by Micromonospora zionensis.

G-52 is a new broad spectrum aminoglycoside produced by a species of the genus Micromonospora, Micromonospora zionensis. It has been differentiated from other known related antibiotics by a variety of chemical and biological methods. Its in vitro and in vivo spectrum of activity appears to be quite similar to that of verdamicin and gentamicin but is differentiated from them by its increased activity against 6'-N-acetylating strains.

A new actinomycin complex produced by a Micromonospora species: fermentation, isolation, and characterization.

A species of Micromonospora, Micromonospora floridensis NRRL 8020, has been found to produce an actinomycin complex consisting of at least 25 active components. After solvent extraction of the complex, separation of the individual components was carried out by preparative thin-layer chromatography. Hydrolysis and subsequent electrophoretic and chromatographic identification of the amino acid content of each of the isolated components have shown differences from known actinomycins, and the probability exists that these contain a number of amino or imino acids not previously found in other members of this group of antibiotics.

Micromonospora-produced gentamicin components.

After the chromatographic separation of [methyl-(14)C]gentamicin major (C) components from a large-scale radioactive fermentation (Lee et al., 1974), [methyl-(14)C]gentamicin minor (polar) components (A, B, B(1), X(2), and G-418) were isolated from subsequent chromatography of the remaining antibiotic mixture. When l-[methyl-(14)C]methionine was added at the onset of biosynthesis of the gentamicin components, incorporation of label into the minor components preceded incorporation into the major components. Degradation occurred when [methyl-(14)C]gentamicin major components (C(1), C(2) and C(1)a) were added respectively to the gentamicin-producing culture medium and shaken.

New polyene antifungal antibiotic produced by a species of Actinoplanes.

A new species of Actinoplanes, which has been deposited with the designation NRRL 5325 at the Northern Utilization Research and Development Division of the U. S. Department of Agriculture, produces a polyene antifungal complex designated as Sch 16656. The complex, consisting of one major and three minor components, is isolated from the fermentation broth by a solvent extraction procedure and purified by precipitation methods. The major component is a heptaene and is highly active in vitro and in vivo against Candida albicans. It is active also against strains of Torulopsis and is significantly more potent orally than candicidin in mice against Candida infections.

Verdamicin, a new broad spectrum aminoglycoside antibiotic.

Verdamicin is a new aminoglycoside antibiotic isolated from fermentation broths of a species of the genus Micromonospora, M. grisea. It has been differentiated from other known related antibiotics by a variety of chemical and biological methods. Its in vitro and in vivo spectrum of activity appears to be similar to those of gentamicin and sisomicin.

Binding of aminoglycoside antibiotics to filtration materials.

An investigation to study adsorption of gentamicin and other related aminoglycoside antibiotics to cellulose, diatomaceous earth (Celite), and Seitz filter sheets was carried out. Experiments with five aminoglycosides indicated that 30 to 100% of these antibiotics was adsorbed to cellulose depending on the ratio of antibiotic to adsorbent, and the total quantity could not be removed by acidification. Similarly, a study with gentamicin found adsorption to diatomaceous earth to be in the range of 33 to 98%. Neomycin and gentamicin were also readily adsorbed to Seitz filter sheets. The data indicate that large losses may occur during filtration of these antibiotics under certain conditions, and care should be taken to properly evaluate results during studies with these compounds in the presence of adsorbent materials.

Binding of aminoglycosides to feces.

Gentamicin and several other basic antibiotics were examined for their ability to adsorb to dog feces. It was found that 44 to 90% of all antibiotics studied were adsorbed to feces depending on the ratio of antibiotic to fecal material. Attempts to extract these antibiotics by acid treatment after adsorption onto feces were only partially successful since large portions of the bound materials were not removed.

Antibiotic G-418, a new Micromonospora-produced aminoglycoside with activity against protozoa and helminths: fermentation, isolation, and preliminary characterization.

Antibiotic G-418 is a new aminoglycoside produced as the major component by a new species of Micromonospora, M. rhodorangea NRRL 5326. The antibiotic is prepared by submerged fermentation in a soybean-dextrin medium. Antibiotic G-418 is adsorbed on a cationic-exchange resin and separated from other impurities by passing it down a Dowex (1 x 2) resin column. The antibiotic, which contains 2-deoxystreptamine, has broad-spectrum antibacterial activity and is highly active against protozoa, amoebae, tapeworm, and pinworm infections in mice. This report describes the taxonomy of the organism, and fermentation, isolation, and preliminary characterization of antibiotic G-418.