The effect on winter illness of large doses of vitamin C

Between December 1972 and February 1973, 2349 volunteers participated in a double-blind trial to assess the effect of large doses of vitamin C on the incidence and severity of winter illness. In addition, records were kept but no tablets taken during March. Subjects were randomly allocated to eight treatment regimens: three prophylactic-only (daily dose 0.25, 1 or 2 g), two therapeutic-only (4 or 8 g on the first day of illness), one combination (1 g daily and 4 g on the first day of illness), and two all-placebo. None of the groups receiving vitamin C showed a difference in sickness experience that was statistically significant from that of the placebo groups, but the results obtained were compatible with an effect of small magnitude from both the prophylactic and therapeutic regimens, and an effect of somewhat greater magnitude from the combination regimen. The combination regimen was associated more with a reduction in severity than frequency of illness, although the extra dosage was limited to the first day of illness. In spite of the eightfold range in daily dose, the three prophylactic-only regimens showed no evidence of a dose-related effect, but the 8 g therapeutic dose was associated with less illness than the 4 g therapeutic dose. There was no evidence of side effects from the 1 and 2 g prophylactic doses of vitamin C, and no evidence of a rebound increase in illness during the month following withdrawal of the daily vitamin supplements. On the basis of this and other studies it is suggested that the optimum daily dose of vitamin C is less than 250 mg, except possibly at the time of acute illness, when a larger daily intake may be beneficial.     

Antimutagenic efficacy of higher doses of vitamin C

Vitamin C, when administered concurrently with a pesticide (endosulfan, phosphamidon or mancozeb), could significantly decrease the frequency of pesticide-induced clastogenic and mitosis-disruptive changes in the bone marrow cells of young Swiss albino mice. Of the three doses (10, 20 or 40 mg/kg b.wt./day) of the vitamin, the one which is double the human therapeutic dose (20 mg/kg b.wt./day) was most effective as an antimutagen to be followed by 40 mg and 10 mg. None of these doses of vitamin C showed any genotoxicity of their own for the parameters studied here.     

The effect of large doses of vitamin C and magnesium on stress responses in common carp, Cyprinus carpio.

1. Plasma magnesium, cortisol, lactate and ascorbic acid were examined in common carp subjected to various dietary treatments and following handling stress. 2. Under conditions of satisfied dietary magnesium and ascorbate requirements, plasma cortisol concentration after stress increased less pronouncedly than in fish fed large doses of ascorbate and/or magnesium. 3. Plasma lactate increased significantly in all groups after stress, although the increase seemed to be more severe (detrimental) in fish on large doses of ascorbate, either as ascorbic acid (AA) or ascorbic monophosphate Mg salt (AP). 4. Large doses of dietary ascorbate, both AA and AP, resulted in a significant increase of total ascorbate concentration in kidney and hepatopancreas of carp in comparison to pre-experimental level. 5. Kidney total ascorbate concentration decreased by 10-23% in all groups but one in which fish fed diet supplemented with AA displayed a significant increase (30%) of tissue ascorbate. The opposite trend was found in hepatopancreas of AA group with 21.5% ascorbate depletion. 6. The present results suggest that plasma cortisol and kidney (steroidogenesis site) and hepatopancreas ascorbate concentration responses to stress may not be related. Our results also do not support the hypothesis of the primary role of the high concentration of ascorbate in the kidney inhibiting steroidogenesis.     

Hepcidin expression in the liver: relatively low level in patients with chronic hepatitis C

Patients with chronic hepatitis C frequently have serum and hepatic iron overload, but the mechanism is unknown. Recently identified hepcidin, exclusively synthesized in the liver, is thought to be a key regulator for iron homeostasis and is induced by infection and inflammation. This study was conducted to determine the hepatic hepcidin expression levels in patients with various liver diseases. We investigated hepcidin mRNA levels of liver samples by real-time detection-polymerase chain reaction; 56 were hepatitis C virus (HCV) positive, 34 were hepatitis B virus (HBV) positive, and 42 were negative for HCV and HBV (3 cases of auto-immune hepatitis, 7 alcoholic liver disease, 13 primary biliary cirrhosis, 9 nonalcoholic fatty liver disease, and 10 normal liver). We analyzed the relation of hepcidin to clinical, hematological, histological, and etiological findings. Hepcidin expression levels were strongly correlated with serum ferritin (P < 0.0001) and the degree of iron deposit in liver tissues (P < 0.0001). Hepcidin was also correlated with hematological parameters (vs. hemoglobin, P = 0.0073; vs. serum iron, P = 0.0012; vs. transferrin saturation, P < 0.0001) and transaminase levels (P = 0.0013). The hepcidin-to-ferritin ratio was significantly lower in HCV(+) patients than in HBV(+) patients (P = 0.0129) or control subjects (P = 0.0080). In conclusion, hepcidin expression levels in chronic liver diseases were strongly correlated with either the serum ferritin concentration or degree of iron deposits in the liver. When adjusted by either serum ferritin values or hepatic iron scores, hepcidin indices were significantly lower in HCV(+) patients than in HBV(+) patients, suggesting that hepcidin may play a pivotal role in the pathogenesis of iron overload in patients with chronic hepatitis C.     

Effects and high and low doses of vitamin A on the excitability of frog cardiomyocytes

The effects of the vitamin A lysosomal membrane labilizator on electrophysiological characteristics was investigated on frog cardiomyocytes. Large and small doses of vitamin A produced qualitatively identical effects: decrease of the steepness of action potential (AP) front, decrease of the spike amplitude, shortening of the plateau, decrease of the steepness in the last phase of AP-repolarization. The AP-duration decreased considerably. Large doses of the vitamin also reduced the rest potential level and insignificantly increased the heart contractions frequency. We assume that vitamin A can affect the cardiomyocyte surface membrane permeability, thereby decreasing its excitability due to suppression of the sodium and potassium.     

Neutron dose effect relationships at low doses

Summary Stimulated by recent observations of non-linearity in the dose effect relationship for the transformation of mammalian cells in vitro by fission neutron irradiation and the reverse dose rate effect in this system, the data for mutation induction in the stamen hairs ofTradescantia occidentalis has been re-examined. The non-linear dose effect relationships suggested in the original reports are confirmed both by the dose effect relationships themselves and by an examination of the statistics of the results. This non-linearity also appears to be present in the more recent observations of other workers. It is suggested that the non-linearity in the system may be due to a sub-population of cells in a particularly sensitive phase of the cell cycle at the time of irradiation. There is a possibility that the data also indicate a qualitative difference in the underlying biophysical actions of neutron and photon radiations.Dedicated to Prof. W. Jacobi on the occasion of his 60th birthday     

Antistress effects of vitamin E and dimethylsulfoxide during their combined administration in low doses

Low doses of vitamin E (5 mg/kg body weight) and dimethyl sulfoxide (50 mg/kg) given simultaneously orally to albino rats prevented the disturbances of the behaviour and vegetative functions induced by chronic emotional painful stress. The adaptive effect of vitamin E or dimethyl sulfoxide given alone was much lower or altogether absent. The antioxidant combination used decreased the intensity of lipid peroxidation in the brain and blood serum as well as cholesterol content in brain lipids and activated brain superoxide dismutase and nonenzymatic superoxide scavenging activity of the serum. The results obtained suggest that the combination of vitamin E with dimethyl sulfoxide may be used for the treatment of pathological conditions accompanied by lipid peroxidation syndrome.     

Apoptosis-inducing activity of vitamin C and vitamin K.

Apoptosis-inducing activity of vitamins C and K and of their analogs are reviewed. Vitamin C shows both reducing and oxidizing activities, depending on the environment in which this vitamin is present. Higher concentrations of vitamin C induce apoptotic cell death in various tumor cell lines including oral squamous cell carcinoma and salivary gland tumor cell lines, possibly via its prooxidant action. The apoptosis-inducing activity of ascorbate is stimulated by Cu2+, lignin and ion chelator, and inhibited by catalase, Fe3+, Co2+ and saliva. On the other hand, at lower concentrations, ascorbic acid displays an antioxidant property, preventing the spontaneous and stress or antitumor agent-induced apoptosis. Sodium 5,6-benzylidene-L-ascorbate, intravenous administration of which induces degeneration of human inoperable tumors and rat hepatocellular carcinoma in vivo, induces apoptotic or non-apoptotic cell death, depending on the types of target cells. On the other hand, elevation of intracellular concentration of ascorbic acid by treatment with ascorbate 2-phosphate or dehydroascorbic acid makes the cells resistant to the oxidative stress-induced apoptosis. Vitamin K2, which has a geranylgeranyl group as a side chain,and vitamin K3 induces apoptosis of various cultured cells including osteoclasts and osteoblasts, by elevating peroxide and superoxide radicals. Synergistic apoptosis-inducing actions have been found between vitamins C and K, and between these vitamins and antiproliferative agents. The possible therapeutic application of these vitamins is discussed.     

Effect of low doses of radiation on vitamin A and E levels in rat liver

It has been established that under intake of small doses of 137Cs by rat for 9 months the radioactivity of whole rat body was increased in irregular manner. Under this condition the level of fat-soluble vitamins A and E is decreased and the decrease is well correlated with a level of radionuclide accumulation by rat's body. The possible causes of decrease of the vitamins A and E level under intake of small doses of radionuclide are discussed.     

Prophage induction in lysogenic cultures of bacteria as a test of the biological indication of relatively low doses of gamma radiation

Induction of prophage in lysogenic cultures, Pseudomonas aeruginosa (strain PA01 (PM63)) and Escherichia coli K-12 (strain AB1157 (lambda) pKM101), was proposed as a test for biological indication of gamma-irradiation with relatively low doses. Sufficient resolving power (the sensitivity threshold of the method was 0.25 to 0.5 Gy) and relative simplicity of the practical use of the method were demonstrated. Within the dose range from 0.25 to 10 Gy, the relationship between the value of the prophage induction and radiation dose was linear.     

The effect of extremely low doses of the novel regulatory plant proteins

Searching and study on regulatory proteins, which can keep under control the scope of important processes as like as cell adhesion, proliferation, differentiation and morphogenesis, is an actual aim of the current biochemistry. Recently we have identified S-100 proteins in plants of following species: plantain (Plantago major L.), aloe (Aloe arborescens L.), and bilberry (Vaccinum myrtillus L.). Extraction and purification of S-100 proteins gotten from these plants were performed by the method we developed earlier for adhesion proteins of animal tissues. Homogeneity of the studied plant proteins was evaluated and confirmed by HPLC and SDS-electrophoresis in PAAG. Both, plant and animal proteins have appeared to be biologically active at extremely low doses. The tests were performed by adhesiometrical method in short-term tissue culture of mouse's liver in vitro. As a result it was established that the plant proteins insert a membranotropic effect being added in extremely low doses, corresponding to 10(-10)-10(-13) mg/ml. Keeping in mind that the plantain is well known remedy for wound protection and healing, in several experiments we studied the biological effect of plant S-100 proteins on animal cells. It was found that S-100 proteins obtained from plantain influences proliferation of human fibroblasts in vitro. It was found that after the treatment with this protein in low doses the cell growth rate increases essentially.     

Protective effect of low doses in mutagenesis with ethylene oxide in E. coli

The influence of pre-exposure to low doses of ethylene oxide (EtO) on the frequency of leu+ revertants in the E. coli strain, WU36-10, and its excision-repair-deficient mutant, WU36-10-89, after treatment with high doses of EtO, was studied. Low doses had an adaptive effect in both strains with respect to high doses of EtO which was manifested by a decreased number of revertants and lower lethality.