Effect of sigetin on triglyceride and cholesterol levels in rat blood and liver

Sigetin, a dihydrostilbestrol analog but without estrogenic action, lowers the cholesterol concentration in intact rats and also after administration of dexamethasone. Sigetin prevents the elevation of the blood triglyceride level observed in rats under the influence both of diethylstilbestrol and other agents, notably ethanol and dexamethasone.Laboratory of Experimental Pharmacotherapy of Atherosclerosis, Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. (Presented by Academician of the Academy of Medical Sciences of the USSR A. N. Klimov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 87, No. 2, pp. 151–153, February, 1979.     

Effect of short-term starvation versus high-fat diet on intramyocellular triglyceride accumulation and insulin resistance in physically fit men

It is currently believed that intramyocellular triglyceride (IMTG) accumulation and insulin resistance are a consequence of dietary fat ingestion and/or the elevated circulating lipid levels associated with chronic fat surplus. The purpose of this study was to compare the effect of short-term starvation versus low-carbohydrate (CHO)/high-fat diet on IMTG accumulation and the development of insulin resistance in physically fit men. Intramyocellular triglyceride content, measured as intramyocellular lipid (IMCL) by proton magnetic resonance spectroscopy (1H-MRS), and glucose tolerance/insulin sensitivity, assessed by frequently sampled intravenous glucose tolerance test (IVGTT), were determined after 67 h of: (a) water-only starvation (S); and (b) very low-CHO/high-fat diet (LC). These diets had in common significant restriction of CHO availability but large differences in fat content. All results were compared with those measured after a mixed CHO diet (C). Dietary interventions were administered by cross-over design. The level of dietary-induced IMTG accumulation (P = 0.46), insulin resistance (P = 0.27) and glucose intolerance (P = 0.29) was not different between S and LC treatments. Intramyocellular triglyceride content and insulin sensitivity were negatively correlated (r = -0.63, P < 0.01). Therefore, whilst insulin resistance may be due to fat accumulation at a cellular level, in the integrated human organism this outcome is not exclusively a function of dietary fat intake. The comparable level of IMTG accumulation and insulin resistance following S and LC may suggest that these metabolic perturbations are largely a consequence of the increased lipolytic response associated with CHO restriction.     

Effect of fasting on the metabolism in rat aorta

The oxidation of 14C-labelled glucose, beta-hydroxybutyrate and palmitate to CO2 and the incorporation of 14C-labelled amino acid into alkali-soluble protein were studied in aorta from fed and fasted male Sprague-Dawley rats, weighting about 200 g. Substrate oxidation and amino acid incorporation were measured during incubation of rat aorta in vitro for 2-3 h. After fasting for 6 h there was a slight but significant increase in the plasma concentration of beta-hydroxybutyrate. Blood glucose was lowered after 12 h while an increase in the plasma concentration of free fatty acids was found after 24 h. A decrease in the oxidation of glucose in rat aorta was found after fasting for 12 h and with prolonged fasting a further decrease in the aortic glucose oxidation was found. After fasting for 4 days the oxidation of beta-hydroxybutyrate and the incorporation of 14C-leucine and 14C-phenylalanine into protein were reduced in rat aorta while the oxidation of palmitate was not altered. The effects of fasting on substrate oxidation and amino acid incorporation in rat aorta, found in this study are similar to the known effects of diabetes on vascular metabolism.     

APOC3, CETP, fibrinogen, and MTHFR are genetic determinants of carotid intima-media thickness in healthy men (the Stanislas cohort)

The purpose of this study was to examine the relationship between carotid intima-media thickness (CIMT) inter-individual variability and 16 polymorphisms of 11 genes associated with cardiovascular risk factors (genes among lipid and homocysteine metabolisms, blood viscosity, platelet aggregation, leukocyte adhesion and renin-angiotensin system). CIMT was measured by high resolution B-mode ultrasonography in an healthy population of 77 men and 84 women, aged 35-54 years and selected from a French Cohort: the Stanislas Cohort. The polymorphisms studied were genotyped by a multilocus approach. Statistical analyses were carried out by ANOVA, after adjustment of CIMT for age, body mass index, and smoking, and by multiple regression analyses. No association was found with APOB Thr71Ile, APOC3 -482C/T, -455T/C, GpIIIa P1A, AT1R 1166A/C, AGT Met235Thr, CBS Ile278Thr, SELE 98G/T, and SELE Ser128Arg, polymorphisms neither in men nor in women. Although, in women we did not find any association for APOC3 3206T/G, 3175C/G, 1100C/T, CETP Ile405Val, MTHFR 677C/T and fibrinogen -455G/A polymorphisms; in men these polymorphisms were associated with CIMT variability (p< or =0.01; p< or =0.05). The most interesting finding was that altogether these genes in men were able to explain a considerable part, 20.6%, of CIMT variability. Therefore, our study gives a new opportunity to understand CIMT variability.     

Effect of age on substance P levels in the rat mesenteric artery and vein

The content of substance P in the vasculature of Fischer 344 rats 6 to 27 months of age was determined by radioimmunoassay. Substance P could not be measured in the subclavian vein, femoral artery and vein or cerebral arteries of 6 month old rats. Levels of substance P in the mesenteric artery and vein of 6 month old rats averaged 4.8 +/- 1.0 and 8.3 +/- 1.8 pmole/g wet weight (n = 6-7), respectively. At 20 months of age, substance P levels in the vein were significantly increased. At 27 months, levels of substance P in both mesenteric artery and vein were increased to almost twice the values found in younger animals. This increased substance P content could reflect increased nerve density, or, more likely, an increased substance P content in each nerve ending. In the latter case, it is not possible to distinguish between increased content due to decreased nerve activity or increased content which would result in increased amounts of substance P released with each nerve impulse.     

Effect of Brn-3a deficiency on primary nociceptors in the trigeminal ganglion

Immunohistochemistry for substance P, somatostatin and vanilloid receptor subtype 1 as well as receptors for somatostatin and opioids was performed on the trigeminal ganglion in wild-type and Brn-3a knockout mice at postnatal day 0. In wild-type mice, the trigeminal ganglion contained abundant substance P-, vanilloid receptor subtype 1-, sst2A receptor- and delta-opioid receptor-immunoreactive neurons, while the ganglion had only a few mu-opioid receptor-immunoreactive neurons. The Brn-3a deficiency had an effect on the cell size but not the number of substance P-immunoreactive neurons. In knockout mice, the proportion of small immunoreactive neurons markedly increased and that of medium- to large-sized immunoreactive ones correspondingly decreased (mean +/- S.D. = 54.7 +/- 29.1 microm2, range = 10.9-220.8 microm2) compared to wild-type mice (mean +/- S.D. = 116.6 +/- 58.6 microm2, range = 27.3-400.7 microm2). As for vanilloid receptor subtype 1-immunoreactive neurons, the number and cell size was barely affected by the deficiency. On the other hand, the loss of Brn-3a caused a decrease in the number of sst2A receptor- or delta-opioid receptor-immunoreactive neurons (more than 95% reduction) and an increase in the number of mu-opioid receptor-immunoreactive neurons (9.3-fold increase). Somatostatin-immunoreactive neurons were not detected in the trigeminal ganglion of wild-type or mutant mice at postnatal day 0. The present study suggests that Brn-3a deficiency may have effects on the survival of trigeminal nociceptors and their expression of some neurochemical substances.     

Effect of triglyceride levels on methyl and methylene envelope line widths in proton nuclear magnetic resonance spectroscopy of human plasma

Recent studies have described a relation between the line widths of the methyl and methylene resonance envelopes in the proton nuclear magnetic resonance spectrum of human plasma and the occurrence of cancer. An average line width of less than 33 Hz has been reported to correlate with the presence of cancer, whereas greater line widths have not. In 26 normal volunteers, we found a significant inverse correlation between fasting triglyceride level and plasma spectral line width. We also observed that dietary lipids have measurable effects on spectral line widths. In another sample of seven normal persons (three of whom had elevated plasma triglyceride levels), the line widths of whole plasma varied widely (mean, 35.6 +/- 8.8 Hz); however, the mean line widths of the lipoprotein fractions isolated from those samples differed greatly, but the variance within each fraction was small (very-low-density lipoprotein, 22.0 +/- 1.9 Hz; low-density lipoprotein, 35.0 +/- 2.8; high-density lipoprotein, 28.8 +/- 1.9). The results of this study indicate that the plasma triglyceride level has a profound effect on the average spectral line width of plasma. This effect can be explained by the relative amounts of lipoprotein fractions in whole plasma. Plasma triglyceride concentrations of more than 1.24 mmol per liter (greater than 110 mg per deciliter), whatever the source, produce average plasma methyl and methylene line widths of less than 33 Hz.     

Frequency of the cystic fibrosis 3199del6 mutation in individuals heterozygous for I148T

Purpose: To determine the carrier frequency of the 3199del6 cystic fibrosis (CF) mutation in individuals heterozygous for I148T in a large-scale CF testing population.Methods: DNA samples from 439 consecutive I148T-heterozygous individuals were screened for the 3199del6 mutation using a laboratory-developed test.Results: Genotyping revealed four samples heterozygous for the 3199del6 mutation (0.9%). The four samples positive for 3199del6 had an IVS 8 genotype of 7T/9T. The 3199del6 mutation was not observed after genotyping of 348 random, anonymous samples.Conclusion: The 3199del6 mutation occurs in 0.9% of individuals positive for the I148T mutation and < 0.07% of chromosomes that are wild type for the ACMG panel mutations.     

The effect of increased respiratory resistance on glycogen and triglyceride levels in the respiratory muscles of the rat

Summary The effect of increased respiratory resistance (stenosis of the trachea) on glycogen and triglyceride levels in the diaphragm (D) and intercostal (external-IE, internal-II) muscles was studied in the rat. Tracheal stenosis resulted in a reduction of glycogen level in the muscles. For the fed rats the reductions were: D-45 and 79%, IE-14 and 30%, II-14 and 35%, 0.5 and 3 h after stenosis, respectively. For rats fasted for 24 h the reductions were: D-64 and 86%, IE-33 and 71%, II-40 and 82%, after 0.5 and 3 h respectively. The level of triglycerides in the muscles was stable during stenosis in the fed group, whereas in the fasted group it were reduced in the diaphragm by 50% after 0.5 h, and by 52% after 3 h. It is concluded that both endogenous and blood-born energy fuels are utilized by the respiratory muscles during increased resistance breathing. The work was supported by Polish Academy of Sciences (10.4.)     

Effect of complement component C3 deficiency on experimental Lyme borreliosis in mice

Mice deficient in complement component C3 (C3(-/-)) and syngeneic C57BL/6 control mice were challenged with Borrelia burgdorferi to determine the role of complement in immune clearance and joint histopathology during experimental Lyme borreliosis. Tibiotarsal joint, ear, and heart tissues were monitored for spirochete numbers at 2, 4, 8, and 12 weeks postinoculation with 10(5) B. burgdorferi B31 clone 5A4 by using quantitative real-time PCR. The spirochete load in joint and ear tissue remained higher in the C3(-/-) mice than in the wild-type counterparts throughout the 12-week study, whereas the numbers in heart tissue of both groups of mice decreased substantially at 8 to 12 weeks postinfection. Histopathology scores for joint tissue were generally higher in the C3(-/-) mice compared to C57BL/6 controls at 2 and 4 weeks postinfection, which may reflect the presence of higher numbers of bacteria in the joints at these early time points. Levels of anti-B. burgdorferi immunoglobulin G tended to be reduced in the C3(-/-) mice compared to control mice. Furthermore, a 5.5-fold-lower number of the complement-sensitive Borrelia garinii was needed to infect C3(-/-) mice compared to C57BL/6 mice, indicating that its sensitivity to complement is one barrier to infection of the mouse model by B. garinii. These results indicate that the complement system may be important in controlling the early dissemination and progression of B. burgdorferi infection.     

The effect of betaine treatment on triglyceride levels and oxidative stress in the liver of ethanol-treated guinea pigs

We investigated the effect of betaine supplementation on ethanol induced steatosis and alterations in prooxidant and antioxidant status in the liver of guinea pigs. Animals were fed with normal chow or betaine containing chow (2% w/w) for 30 days. Ethanol (3 g/kg, i.p.) was given for the last 10 days. We found that ethanol treatment caused significant increases in plasma transaminase activities, hepatic triglyceride and lipid peroxide levels. Significant decreases in glutathione (GSH), -tocopherol and total ascorbic acid (AA) levels were also observed, but hepatic superoxide dismutase, glutathione peroxidase and glutathione transferase activities remained unchanged as compared with those in controls. Betaine treatment together with ethanol in guinea pigs is found to decrease hepatic triglyceride, lipid peroxide levels and serum transaminase activities and to increase GSH levels. No changes in a-tocopherol and total AA levels and antioxidant enzyme activities were observed with betaine treatment in alcohol treated guinea pigs. In addition, histopathological assessment of guinea pigs showed that betaine reduced the alcoholic fat accumulation in the liver. Based on these data, betaine treatment has a restoring effect on the alterations in triglyceride, lipid peroxide and GSH levels following ethanol ingestion.     

Evaluation of admission levels of P,E and L selectins as predictors for thrombosis in hospitalized COVID-19 patients

Thromboembolic complications are the most reported cause of death in coronavirus disease-2019 (COVID-19). Hypercoagulability, platelets activation and endotheliopathy are well-recognized features in COVID-19 patients. The aim of this work was to evaluate circulating soluble selectins P, E and L at the time of hospital admission as predictors for upcoming thrombosis. This retrospective study included 103 hospitalized COVID-19 patients and 50 healthy volunteer controls. COVID-19 patients were categorized into two groups; group 1 who developed thrombosis during hospitalization and group 2 who did not. Soluble selectins were quantitated using ELISA technique. Higher levels of sP-selectin, sE-selectin and sL-selectin were detected in COVID-19 patients compared to controls. Furthermore, significantly higher levels were found in group 1 compared to group 2. Their means were [5.86 ± 1.72 ng/mL vs. 2.51 ± 0.81 ng/mL]; [50 ± 8.57 ng/mL vs. 23.96 ± 6.31 ng/mL] and [4.66 ± 0.83 ng/mL vs. 2.95 ± 0.66 ng/mL] for sP-selectin, sE-selectin and sL-selectin respectively. The elevated selectins correlated with the currently used laboratory biomarkers of disease severity. After adjustment of other factors, sP-selectin, sE-selectin and sL-selectin were independent predictors for thrombosis. At sP-selectin ≥ 3.2 ng/mL, sE-selectin ≥ 32.5 ng/mL and sL-selectin ≥ 3.6 ng/mL thrombosis could be predicted with 97.1%, 97.6% and 96.5% sensitivity. A panel of the three selectins provided 100% clinical sensitivity. Admission levels of circulating soluble selectins P, E and L can predict thrombosis in COVID-19 patients and could be used to identify patients who need prophylactic anticoagulants. E-selectin showed a superior clinical performance, as thrombo-inflammation biomarker, to the most commonly studied P-selectin.