3-Hydroxy-3-methylglutaric acid and triton-induced hyperlipidemia in rats.

3-Hydroxy-3-methylglutaric acid (HMG) significantly decreased cholesterol, triglyceride and phospholipid levels in whole serum, serum beta-lipoproteins and liver of Triton-induced hyperlipidemic rats. Therapeutically 50 mg HMG/kg is equivalent to 200 mg nicotinic acid/kg in lowering all these lipid parameters. HMG may exert its hypolipidemic effect through inhibition of lipoprotein synthesis.     

3-Hydroxy-3-Methylglutaric acid and triton-induced hyperlipidemia in rats

Summary 3-Hydroxy-3-methylglutaric acid (HMG) significantly decreased cholesterol, triglyceride and phospholipid levels in whole serum, serum -lipoproteins and liver of Triton-induced hyperlipidemic rats. Therapeutically 50 mg HMG/kg is equivalent to 200 mg nicotinic acid/kg in lowering all these lipid parameters. HMG may exert its hypolipidemic effect through inhibition of lipoprotein synthesis.Acknowledgments. We are grateful to Dr.M. Saleemuddin for encouragement, Dr.P. E. Schurr, Upjohn Co. USA for generous gift of Triton W. R 1339 and Lady Tata Memorial Trust (India) for financial assistance to one of us (SYKY).     

Effect of 3-hydroxy-3-methylglutaric acid on blood lipids in normal and cholesterol-fed rats

Zusammenfassung Intraperitonale Verabreichung von 3-Hydroxy-3-Methylglutarsäure setzt bei normalen Ratten den Serumspiegel von Cholesterin, Cholesterinestern, Esterfettsäuren und Triglyceriden signifikant herab. Bei einer cholesterinreichen Diät werden die Konzentrationen von Cholesterin und seinen Estern, bei hyperlipämischen Tieren die des Cholesterins im Serum nicht herabgesetzt. Die übrigen Lipidfraktionen verhalten sich wie im ersten Versuch.     

Hypocholesterolemic effect of 3-hydroxy-3-methylglutaric acid

Zusammenfassung Bei Fütterung mit 3-hydroxy-3-methylglutarsäure (HMG) wurde eine bedeutende Senkung des Serum-Cholesterinspiegels sowohl in normalen, als auch in hypercholesterin-ämischen Ratten beobachtet. Bei gleichzeitiger Verabreichung von HMG und Cholesterol blieb die erwartete Zunahme beim Serumcholesterin aus und gleichzeitig wurde eine Abnahme des Cholesterinspiegels festgestellt.     

Dissolution of gallstones in hamsters by 3-hydroxy-3-methylglutaric acid

Summary Addition of 0.05–0.20% of 3-hydroxy-3-methylglutaric acid to a lithogenic hamster diet resulted in a marked reduction in the incidence of gallstones in hamsters.Supported, in part, by grants HL-03299, AG-00076 and T32 CA-09171 and a Research Career Award, HL-0734 from the National Institutes of Health.     

Effect of 3-hydroxy-3-methylglutaric acid on hypercholesterolemic liver

Zusammenfassung Fütterung mit 3-hydroxy-3-Methylglutarsäure (HMG) führt bei hypercholesterin-ämischen Ratten zu einer bedeutenden Senkung des Leber-Cholesterinspiegels. Gleichzeitige Verabreichung von HMG und Cholesterol oder von Cholesterol allein ergab eine geringe Zunahme des Cholesterolspiegels im ersten Fall. Die histopathologische Leberuntersuchung zeigte, dass HMG-Behandlung eine schnelle Normalisierung der Fettveränderungen verursachte, ohne dass toxische Wirkung auf die Zellgewebe auftrat.     

Type VI collagen in experimental atherosclerosis

Summary Diffuse intercellular immunofluorescence staining of type VI collagen was found in the experimentally thickened vascular wall and in control blood vessel tissues as well, superimposed by more intense staining around basement membranes. While the basement membrane staining disappeared in advanced mural thickenings, the diffusely distributed network of type VI collagen remained.     

Type VI collagen in experimental atherosclerosis

Diffuse intercellular immunofluorescence staining of type VI collagen was found in the experimentally thickened vascular wall and in control blood vessel tissues as well, superimposed by more intense staining around basement membranes. While the basement membrane staining disappeared in advanced mural thickenings, the diffusely distributed network of type VI collagen remained.     

The use of crocetin in experimental atherosclerosis

Résumé L'action préventive de la crocetine de l'apparition de l'artério-sclerose sur l'aorte du lapin soumis à un régime hypercholestérolémiant est démontrée. Par contre le mécanisme d'action de cette substance n'est pas élucidé par les expériences relatées.     

Formation of indolyl-3-acetylaspartic acid in rats

Summary Indolyl-3-acetylaspartic acid (IAAsp) was detected in the urine of rats given indolyl-3-acetic acid (IAA) i.p. It was ascertained that the conversion of IAA into IAAsp could be carried out not only in plants but also in animals.     

Influence of vitamin A on experimental atherosclerosis in rabbits

Résumé La vitamine A a eu un effet hypocholestérimique modéré (7 à 43%) sur des lapins nourris de 0.2% cholestérol. La gravité de l'athérosclérose moyenne fut réduite de 31% dans la crosse aortique, et de 61% dans l'aorte abdominale. L'administration de vitamine A aux lapins nourris de cholésterol a réduit les niveaux de sérum -glucuronidase d'une manière significative, il est donc possible que cette vitamine ait une influence stabilisatrice sur le lysosome.     

The increase of thiobarbituric acid reacting substances in rats with experimental chronic hypoxia

Summary Feeding under conditions of reduced oxygen supply prompted an increase in serum, arterial and brain tissue levels of thiobarbituric acid (TBA)-reacting substances. These observations indicated the possibility that hypoxia might be one of the factors predisposing to the accumulation of lipid peroxide.     

Alpha-amylase inhibitor increases plasma 3-hydroxybutyric acid in food-restricted rats

The effect on energy metabolism of delayed absorption of starch by inhibition of -amylase was examined by considering levels of plasma glucose and 3-hydroxybutyric acid (3-OHBA) in rats. Addition of -amylase inhibitor (AI) to a high starch diet delayed the plasma glucose response after feeding: peak plasma glucose levels in the control group occurred 15 min after feeding, whereas in the AI group this peak did not occur until 30 min after. The total plasma glucose response was not different between the two groups. Plasma 3-OHBA levels 1 day after food restriction increased approximately five-fold in both groups. After 3 days of food restriction, the AI group maintained the same level of plasma 3-OHBA as after 1 day of food restriction, while the control group showed significantly decreased levels of 3-OHBA. After 3 days of food restriction, plasma insulin levels were significantly decreased in the AI group compared with the corresponding levels of the control group and with levels before the restriction. There was no significant difference in body weight between the two groups. These findings suggest that delayed hyperglycemia due to delayed absorption of starch following AI loading may attenuate insulin secretion, leading to altered metabolism of 3-OHBA during the delayed response to energy deficit.     

Tissue distribution and nucleic acid binding of chlorambuci-3H in tumor-bearing rats

Summary In tumour and normal rat tissues prolonged alkylation of DNA and RNA by chlorambucil-³H occurs over periods of 24 h. It is suggested that this may indicate the slow release of an alkylating moiety from an intracellular drugmacromolecule complex.     

Effect of Royal Jelly on serum lipids in experimental animals and humans with atherosclerosis

The primary objective of this review was to assess the size and consistency of Royal Jelly (RJ) effect on serum lipids in experimental animals and humans. The data from animal studies were pooled, where possible, and statistically evaluated by Student's t-test. Meta-analysis was used for the evaluation of human trials. It was found that RJ significantly decreased serum and liver total lipids and cholesterol levels in rats and rabbits and also retarded the formation of atheromas in the aorta of rabbits fed a hyperlipemic diet. Meta-analysis of the controlled human trials of RJ to reduce hyperlipidemia showed a significant reduction in total serum lipids and cholesterol levels and normalization of HDL and LDL as determined from decrease in β/α lipoproteins. The best available evidence suggests that RJ at approximately 50 to 100 mg per day, decreased total serum cholesterol levels by about 14%, and total serum lipids by about 10% in the group of patients studied.     

3-Hydroxy-4-methoxyphenethylamine,the cardioactive constituent of a soft coral

Summary Intravenous administration to rats of the aqueous extract of the soft coralNephthea sp. caused an increase in heart rate and blood pressure. The cardioactive constituent was isolated and shown to be 3-hydroxy-4-methoxyphenethylamine.     

Autoradiographic studies on the experimental pulmonary fibrosis of rats after H3-proline injection

Zusammenfassung Mit einer 2-, 4-, 8- und 16-Wochenbehandlung wurde bei Ratten experimentell eine Lungenfibrose durch SiO₂ verursacht. Später wurde i.p. H³-Prolin injiziert und durch Autoradiographie die pulmonale Fibrose bewertet. In den Pneumokoniose-Herden wurde die Radioaktivität mit der Zeit am intensivsten, wobei die höchste Aktivität in den Kollagenfasern gemessen wurde.     

The biliary excretion of [3H] lysergic acid diethylamide in Wistar and Gunn rats.

The biliary excretion of [3H] LSD was studied in Wistar and homozygous Gunn rats. In Wistar rats approximately 46% of the given dose was recovered from bile in 2.5 h whilst in the homozygous Gunn rat 26% was recovered in the same time period. In both strains the main metabolites were glucuronides.     

The histochemistry of the dehydrogenase systems in the aortae of rabbits with experimental atherosclerosis

Zusammenfassung In Aorten von Kaninchen mit experimenteller Atherosklerose wurden die folgenden Dehydrogenasen untersucht: DPN-Diaphorase, Lactat- und Malat-Dehydrogenase, TPN-Diaphorase, Succinat-, Glucoso-6-phosphat-und Glutamat-Dehydrogenase. Die Aktivität der fünf erstgenannten war in den Endothelien, Makrophagen (Lipophagen) und Fibrozyten der verdickten Intima und kleiner atherosklerotischer Beete deutlich erhöht. Die Befunde stehen im Einklang mit der Ansicht, dass die Stoffwechselaktivität der Intima am Anfang der experimentellen Atherogenesis erhöht ist.

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Further work on the dehydrogenase systems in plaques in rabbit, rats, and humans is in progress and will be reported in detail elsewhere.     

Valproic acid attenuates inflammation in experimental autoimmune neuritis

Valproic acid (VPA) is a short-chain branched fatty with anti-inflammatory, neuro-protective and axon-remodeling effects. We investigated the effects of VPA in rats in which experimental autoimmune neuritis (EAN) had been induced (EAN rats). VPA (300 mg/kg, intraperitoneally) administration to EAN rats once daily immediately following immunization significantly suppressed mRNA levels of interferon-γ, tumor necrosis factor-α, interleukin (IL)-1β, IL-4, IL-6 and IL-17 in the lymph nodes of EAN rats. In peripheral blood and sciatic nerves of EAN rats, Foxp3⁺ cells were increased but IL-17⁺ cells were decreased during VPA treatment. Furthermore, suppressive and therapeutic treatment with VPA greatly attenuated both accumulation of macrophages, T cells and B cells, and demyelination in sciatic nerves, and greatly reduced the severity and duration of EAN. In summary, our data demonstrated that VPA could effectively suppress inflammation in EAN, suggesting that VPA could be a potent candidate for treatment of autoimmune neuropathies.