Randomized cross-over trial of short-term water-only fasting: metabolic and cardiovascular consequences.

BACKGROUND AND AIMS: Routine, periodic fasting is associated with a lower prevalence of coronary artery disease (CAD). Animal studies show that fasting may increase longevity and alter biological parameters related to longevity. We evaluated whether fasting initiates acute changes in biomarker expression in humans that may impact short- and long-term health. METHODS AND RESULTS: Apparently-healthy volunteers (N = 30) without a recent history of fasting were enrolled in a randomized cross-over trial. A one-day water-only fast was the intervention and changes in biomarkers were the study endpoints. Bonferroni correction required p ≤ 0.00167 for significance (p < 0.05 was a trend that was only suggestively significant). The one-day fasting intervention acutely increased human growth hormone (p = 1.1 × 10⁻4), hemoglobin (p = 4.8 × 10⁻7), red blood cell count (p = 2.5 × 10⁻6), hematocrit (p = 3.0 × 10⁻6), total cholesterol (p = 5.8 × 10⁻5), and high-density lipoprotein cholesterol (p = 0.0015), and decreased triglycerides (p = 1.3 × 10⁻4), bicarbonate (p = 3.9 × 10⁻4), and weight (p = 1.0 × 10⁻7), compared to a day of usual eating. For those randomized to fast the first day (n = 16), most factors including human growth hormone and cholesterol returned to baseline after the full 48 h, with the exception of weight (p = 2.5 × 10⁻4) and (suggestively significant) triglycerides (p = 0.028). CONCLUSION: Fasting induced acute changes in biomarkers of metabolic, cardiovascular, and general health. The long-term consequences of these short-term changes are unknown but repeated episodes of periodic short-term fasting should be evaluated as a preventive treatment with the potential to reduce metabolic disease risk. Clinical trial registration (ClinicalTrials.gov): NCT01059760 (Expression of Longevity Genes in Response to Extended Fasting [The Fasting and Expression of Longevity Genes during Food abstinence {FEELGOOD} Trial]).

An immunomodulatory procedure that stabilizes transgene expression and permits readministration of E1-deleted adenovirus vectors.

Immune responses against E1-deleted adenovirus vectors and/or their transgene products result in the rapid elimination of vector-transduced cells and the generation of neutralizing antibodies. Different strategies of immunomodulation to stabilize transgene expression at therapeutic levels and to permit productive vector readministration have been examined. Our previous studies have shown that depletion of macrophages from spleen and liver decreases hepatic inflammation, significantly prolongs transgene expression, and delays the onset of humoral immune responses after systemic administration of an E1-deleted adenovirus vector. In the present study, we have examined the effects of macrophage depletion in combination with temporary blockade of CD40 ligation on E1-deleted adenovirus vector-mediated gene transfer. Alone, each of these treatments significantly inhibited the humoral immune response against the transgene product and prolonged its expression. Together, these treatments completely stabilized transgene expression and inhibited the production of neutralizing anti-adenovirus antibodies, permitting successful vector readministration. Animals rendered immunologically unresponsive to vector and transgene antigens regained their ability to mount productive immune responses against the vector after recovery of immune function, but remained unresponsive to the transgene product. These experiments demonstrate that this treatment is transient and antigen-specific.

[Effect of A, E, C, P vitamin complex on erythrocyte hemocoagulation properties and platelet aggregation in thrombinemia]. / Vliianie kombinatsii vitaminov A, E, C and P na gemokoaguliatsionnye svoistva éritrotsitov i agregatsiiu trombotsitov pri trombinemii.

The protective effect of A, E, C, P vitamin complex has been experimentally proven to display in a decrease of animal death rate and in limiting the intensity of hemocoagulation shifts in thrombinemia. This effect is stipulated by a decrease in thrombocyte aggregation and in coagulation activity and by the increase of erythrocyte deformation properties. These changes seem to be caused by the effect of vitamins on the phospholipid spectrum, electrolyte transport of ATPases and erythrocyte membrane stability.

[Mechanism of heparin inactivation by thromboplastin (factor III)]. / K mekhanizmu inaktivatsii geparina tromboplastinom (faktorom III).

Thromboplastin (a commercial one and that obtained from different tissues) is shown to inactivate heparin in proportion to the quantity of thromboplastin or to the heparin:thromboplastin ratio. A degree of inactivation of heparin changes after the modification of protein component of thromboplastin by proteases, however there is no dependence between the protein amount in the preparation and its antiheparin activity. Inactivation of heparin by thromboplastin is stipulated by the formation of associations due to electrostatic interactions between the clusters of amino acid protein residues (which dissociate under physiological conditions as bases) and heparin sulphogroups. It is suggested that factor III circulating in blood flow participates in the creation of hemostatic potential not only as a result of its ability to catalyze thrombinogenesis, but also due to the decrease of the anticoagulant blood activity.

[Effect of anticonvulsant agents, inducers of microsomal oxidation, on the B-link of immunity and on the natural cytotoxicity of lymphoid organ cells in rats]. / Vliianie protivosudorozhnykh sredstv--induktorov mikrosomal'nogo okisleniia na B-zveno immuniteta i estestvennuiu tsitotoksichnost' kletok limfoidnykh organov krys.

Administration of phenobarbital, benzonal and benzobamil in a dose of 1/20 of LD50 to rats was shown to be followed by phase changes in the system of microsomal oxidation of the liver--activation in the first days after administration with the subsequent (in 1-3 months) decrease of the activity. The drugs activate the specific link of immunity directed at detoxication of the administered substances: increase the level of specific antibody-forming cells in the spleen and antibodies in the peripheral blood. Benzonal and bezobamil enhance the killing activity of cells of the thymus, phenobarbital and benzonal suppress the natural cytotoxicity of cells of the spleen and peritoneal exudate.