Cardiolipin biosynthesis and remodeling enzymes are altered during development of heart failure

Cardiolipin (CL) is responsible for modulation of activities of various enzymes involved in oxidative phosphorylation. Although energy production decreases in heart failure (HF), regulation of cardiolipin during HF development is unknown. Enzymes involved in cardiac cardiolipin synthesis and remodeling were studied in spontaneously hypertensive HF (SHHF) rats, explanted hearts from human HF patients, and nonfailing Sprague Dawley (SD) rats. The biosynthetic enzymes cytidinediphosphatediacylglycerol synthetase (CDS), phosphatidylglycerolphosphate synthase (PGPS) and cardiolipin synthase (CLS) were investigated. Mitochondrial CDS activity and CDS-1 mRNA increased in HF whereas CDS-2 mRNA in SHHF and humans, not in SD rats, decreased. PGPS activity, but not mRNA, increased in SHHF. CLS activity and mRNA decreased in SHHF, but mRNA was not significantly altered in humans. Cardiolipin remodeling enzymes, monolysocardiolipin acyltransferase (MLCL AT) and tafazzin, showed variable changes during HF. MLCL AT activity increased in SHHF. Tafazzin mRNA decreased in SHHF and human HF, but not in SD rats. The gene expression of acyl-CoA: lysocardiolipin acyltransferase-1, an endoplasmic reticulum MLCL AT, remained unaltered in SHHF rats. The results provide mechanisms whereby both cardiolipin biosynthesis and remodeling are altered during HF. Increases in CDS-1, PGPS, and MLCL AT suggest compensatory mechanisms during the development of HF. Human and SD data imply that similar trends may occur in human HF, but not during nonpathological aging, consistent with previous cardiolipin studies.     

Type I Antifreeze Proteins Enhance Ice Nucleation above Certain Concentrations

In this study, we examined the effects that antifreeze proteins have on the supercooling and ice-nucleating abilities of aqueous solutions. Very little information on such nucleation currently exists. Using an automated lag time apparatus and a new analysis, we show several dilution series of Type I antifreeze proteins. Our results indicate that, above a concentration of ∼8 mg/ml, ice nucleation is enhanced rather than hindered. We discuss this unexpected result and present a new hypothesis outlining three components of polar fish blood that we believe affect its solution properties in certain situations.     

Correlation of 19F-NMR spectra of halothane in rat tumor and non-tumor tissues with membrane alterations

The membrane environments in normal and tumor rat tissue and the effect of hyperthermia thereon are studied with 19F-NMR spectroscopy of the general anesthetic halothane. Normal and tumor cell types are clearly differentiated by the halothane resonance. A hydrophobic environment prominent in tumor tissue is more sensitive to heat treatment than the corresponding environments of normal cells. Studies of extracted lipids suggest that this may be due in part to the considerable difference in lipid temperature response which exists between normal and kidney tumor cells.     

Enumeration of potentially pathogenic bacteria from sewage sludges.

To ascertain the health risks that may be posed by the land application of sewage sludges, a scheme was devised to determine the types and numbers of pathogenic and potentially pathogenic bacteria present in sludges. A processing treatment was adapted to sludge to give a homogenate which yielded the greatest numbers of viable bacteria. Conventional methods were successful in enumerating Klebsiella, Staphylococcus, gram-negative enteric bacteria, and commonly used indicator organisms. Modifications of conventional methods improved the enumeration of Salmonella, Mycobacterium sp., fluorescent Pseudomonas sp., and Clostridium perfringens. However, Shigella methodology yielded only one isolate. Utilizing the proposed scheme, the population densities of these organisms were estimated in three domestic wastewater sludges. In light of these results, the potential impact of land application of sewage sludges is discussed.     

Variable mutagenic activity of commercial preparations of ABTS (2,2'-azino-di(3-ethyl-benz-thiazoline) sulphonic acid

Different batches of ABTS obtained from the same commercial source varied in their capacity to effect direct mutation in the strains of Salmonella typhimurium used routinely in the incorporation test of Ames. One batch, obtained in 1976, and another obtained early in 1979, both exhibited direct base-pair substitution and frame-shift activities. These activities, however, were absent from each of two batches obtained after 1979, and also from a highly purified preparation from a different source. The possible presence of the unsulphonated immediate precursor of ABTS as a mutagenic impurity is an unlikely explanation for the activity of the mutagenic preparations. It is more probable that the commercial synthesis generated other, mutagenic, impurities which remained in the batches obtained in 1976 and early in 1979, but were absent or were removed from later batches. The identity of these active impurities is unknown. Pure ABTS is neither a direct nor an indirect mutagen.