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Supplementation with vitamins C and E suppresses leukocyte oxygen free radical production in patients with myocardial infarction
Herbaczynska-Cedro K.; Klosiewicz-Wasek B.; Cedro K.; Wasek W.; Panczenko-Kresowska B.; Wartanowicz M.
Medical Research Centre, Polish Academy of Sciences, Dworkowa 3, 00-754 Warsaw Poland
European Heart Journal (United Kingdom), 1995, 16/8 (1044-1049)

Clinical studies suggest that neutrophil activation during acute myocardial infarction (MI) aggravates tissue injury. Activated neutrophils are an important source of oxygen free radicals (OFR), the injurious effects of which are counteracted by endogenous antioxidants. We have previously shown in healthy subjects that supplementation with antioxidant vitamins C and E suppresses OFR production by isolated neutrophils assayed by chemiluminescence (CL). the present study, performed in patients with acute MI aimed

(1) to investigate the effect of Vitamin-C and E supplementation upon neutrophil OFR production and serum lipid peroxides,

(2) to evaluate serum levels of vitamins C and E in the course of MI.

Forty-five patients with acute MI were randomized to receive either conventional treatment plus Vitamin-C and E aa 600 p.o. for 14 days (VIT,n=23) or conventional treatment only (control, n=22). All measurements were performed on the 1st and 14th day. Neutrophil OFR production assayed by CL decreased significantly in VIT patients (Wilcoxon test for paired data P<0.01, Chi square test P<0.01). In the control group, changes in OFR production were not significant. Serum lipid peroxides (measured as TBARS) increased in controls (P<0.05), but remained stable in VIT patients. Mean (plus or minusSE) serum ascorbic acid and tocopherol on the 1st day were 0.43 plus or minus 0.18mg% and 3.25 plus or minus 1.32 microM.mM -1 cholesterol, respectively, in all patients. On the 14th day in non-supplemented patients mean tocopherol was unchanged, whereas ascorbic acid increased significantly (0.63 plus or minus 0.24 mg%, P<0.01) suggesting that a low basal level was associated at least in part with the acute phase of the disease. An expected increase in serum vitamin levels occurred in VIT patients. In conclusion, supplementation with vitamins C and E suppresses neutrophil OFR production and lowers the marker of lipid peroxidation in patients with MI. These effects, together with a deficiency of antioxidant vitamins, particularly vitamin C in the early phase of the disease, support the view that supplementation with antioxidant vitamins is advisable in patients with MI.

Antioxidant therapy using high dose Vitamin-C: Reduction of postburn resuscitation fluid volume requirements
Matsuda T.; Tanaka H.; Reyes H.M.; Richter H.M. III; Hanumadass M.M.; Shimazaki S.; Matsuda H.; Nyhus L.M.; Baxter C.R.
Department of Surgery/Burn Center, Cook County Hospital, University of Illinois, 700 S. Wood Street, Chicago, IL 60612 USA
World Journal of Surgery (USA), 1995, 19/2 (287-291)

Twenty-four guinea pigs with third degree burns over 70% of the body surface area were divided equally into four groups. At 0.5 hours postburn, all groups received Ringer's lactate solution (R/L) according to the Parkland formula. The infusion rate was then reduced to 25% of the Parkland formula at 1.5 hours postburn. Group 1 received only R/L, and groups 2, 3 and 4 received adjuvant Vitamin-C (14.2 mg/kg/hr) until 4, 8, and 24 hours postburn, respectively. The volume of R/L was reduced by that of Vitamin-C solution so that the hourly sodium and fluid intake in each group was the same. Groups 1 and 2 demonstrated higher hematocrit and lower cardiac output values than did group 3, suggesting hypovolemia and hemoconcentration in these groups. Group 3 showed hematocrit and cardiac output values equivalent to those in group 4. We conclude that high dose Vitamin-C infusion maintains hemodynamic stability in the presence of a reduced resuscitation fluid volume provided Vitamin-C is administered for a minimum of 8 hours postburn.

Vitamin-C reduces ischemia-reperfusion injury in a rat epigastric island skin flap model
Zaccaria A.; Weinzweig N.; Yoshitake M.; Matsuda T.; Cohen M.
Division of Plastic Surgery, University of Illinois, M/C 958, 820 S Wood St, Chicago, IL 60612-7316 USA
Ann. Plast. Surg. (USA), 1994, 33/6 (620-623)

Free radicals have been implicated in the cause of ischemia-reperfusion injury. Various agents have been used in an attempt to reduce ischemia-reperfusion injury pharmacologically, including free radical scavengers. Vitamin-C (ascorbic acid), a well-known free radical scavenger, has not, to the best of our knowledge, been evaluated in this respect. Previous work at our institution has shown that Vitamin-C decreases capillary permeability, thus significantly reducing fluid resuscitation requirements in postburn cases. Because this is due in part to the scavenging effect of Vitamin-C on free radicals, we investigated the role, if any, of Vitamin-C on ischemia-reperfusion injury in a rat epigastric island skin flap model. Twenty-four adult Sprague-Dawley rats were divided into control and vitamin C groups. Superficial epigastric island skin flaps measuring 6.0 x 3.5 cm were raised. Pedicles were isolated and occluded with microvascular clamps for 6 hours. The flaps were then sutured back to their beds over Steri-Drape barriers. Fifteen minutes before reperfusion, the control group flaps were perfused via femoral artery cannulation with normal saline (2.5 ml/kg). The Vitamin-C- treated group was perfused in a similar fashion with 2.5 ml/kg of a Vitamin-C/normal saline solution (27 mg/ml). The animals were observed for 7 days, and the percentage of flap survival was determined using a paper template technique. The Vitamin-C-treated group demonstrated a significantly higher percentage of flap survival than did the control group (25.8% mean vs. 7.5% mean, p < 0.025). In this animal model, Vitamin-C reduced or limited reperfusion injury after 6 hours of ischemia. Its presumed mechanisms of free radical reduction and its relative safety make Vitamin-C a promising area of investigation in future animal studies as well as in human studies examining reperfusion injury.

An experimental study on the protection against reperfusion myocardial ischemia by using large doses of Vitamin-C
Qiao S.; Chen Z.; Song L.
Cardiovascular Institute, CAMS, Beijing 100037 China
Chin. J. Cardiol. (China), 1994, 22/1 (52-54+80)

To obtain the practical measure for the ischemia-reperfusion injury, we developed an open chest pig model (occlusion for 1 hour and reperfusion for 2 hours). Vitamin-C (Vit C 0.2 g/kg) was intravenously given within five minutes to 8 pigs and 12 pigs received only saline as control. The results showed that there were no differences in the hemodynamic parameters, but the release of the creatine kinase isoenzyme after the reperfusion was significantly decreased in the vit C group (P < 0.05-0.01), and the ratio of the infarct area and the risk area was 30.2% in the vit C group and 49.2% in controls respectively (P < 0.05). Furthermore, the content of myocardial malondialdehyde was significantly decreased in the vit C group. In order to observe the protective effect of vitamin C we also developed an open chest rabbit model. After four-hour reperfusion, vit C group had less severe bleeding and milder damage to the capillary endothelium than that of control group. On the rabbit model, the myocardial free radicals were directly measured with the electron resonance spectrograph after one half hour reperfusion (P < 0.05). It was found that the free radical content was significantly elevated in the control group (P < 0.05), vit C could inhibit such elevation (P < 0.01). So it was evident that the protection of vit C was directly related to scavenging the free radicals.

Vitamins as radioprotectors in vivo. I. Protection by Vitamin-C against internal radionuclides in mouse testes: Implications to the mechanism of damage caused by the auger effect
Narra VR, Harapanhalli RS, Howell RW, Sastry KS, Rao DV
Department of Radiology, University of Medicine and Dentistry of New Jersey, Newark 07103.
USA Radiat. Res. (USA), 1994, 137/3 (394-399)

The potential of Vitamin-C, an antioxidant, to protect the radiosensitive spermatogonial cells in mouse testes against the effects of chronic irradiation by radionuclides incorporated into tissue was investigated. Interestingly, when injected intratesticularly, a small and nontoxic amount of Vitamin-C (1.5 microg in 3 microl saline) protected the spermatogonia against the damage associated with high-LET radiation caused by Auger electrons from similarly administered 5-(125I)-iodo-2'-deoxyuridine (125IdU). A dose modification factor (DMF) of 2.3 was obtained. In contrast, no protection was observed when 210Po, an alpha-particle emitter, was administered similarly. These findings suggest that the mechanism of action of the Auger effect is of an indirect nature, which is in contrast to the direct action generally believed to be responsible for biological damage caused by high-LET radiations.

Experimental studies on the treatment of frostbite in rats
Purkayastha S.S.; Chhabra P.C.; Verma S.S.; Selvamurthy W.
Defence Institute of Physiology, and Allied Sciences, Delhi Cantt 110010 India
Indian J. Med. Res. Sect. B Biomed. Res. Other than Infect. Dis. (India), 1993, 98/Aug. (178-184)

The effect of treatment by high dose of Vitamin-C, rapid rewarming by 37degreeC water alone and with Vitamin-C, rapid rewarming by 37degreeC decoction of Indian black tea alone and with vitamin C for experimentally produced frostbite was evaluated in 6 groups (25 each) of rats. Frostbite was produced experimentally in the hind limbs by exposing the animals at -15degreeC for 1h using the harness technique. The degree of injury was assessed and classified on the basis of tissue necrosis at the end of 15 days. Administration of high dose of Vitamin-C for prolonged period and rapid rewarming at 37degreeC water bath immediately after cold exposure apparently reduced the tissue damage. High dose of Vitamin-C therapy preceded by rapid rewarming in plain water showed additional benefit. Rapid rewarming in decoction of Indian tea resulted in identical beneficial effect. The degree of tissue preservation was highest with rapid rewarming in tea decoction followed by high dose of Vitamin-C.

The effects of high-dose Vitamin-C therapy on postburn lipid peroxidation
Matsuda T, Tanaka H, Yuasa H, Forrest R, Matsuda H, Hanumadass M, Reyes H
Burn Center, Cook County Hospital, Chicago, IL 60612 USA
J. Burn Care Rehabil. (USA), 1993, 14/6 (624-629)

The effects of Vitamin-C treatment (14 mg/kg/hr) on postburn lipid peroxidation were evaluated in 12 dogs. A lymph duct above the ankle was cannulated bilaterally. Hourly lymph flow rates, plasma and lymph total protein concentrations, and plasma and lymph malondialdehyde concentrations were measured before the burn injury and for 24 hours after the burn injury. Four groups were employed: nonburn without treatment, nonburn with Vitamin-C treatment, burn without treatment, and burn with Vitamin-C treatment. The nonburn groups showed no significant differences in lymph flow rates, total protein flux, or lymph malondialdehyde level. In the burn groups the postburn hourly lymph flow rate increased by 850% without treatment and by 500% with Vitamin-C treatment, whereas the postburn hourly total protein flux increased by fiftyfold and twentyfold, respectively. There was a significant reduction in the postburn lymph malondialdehyde level in the group treated with Vitamin-C as compared with the nontreatment group. We conclude that high-dose Vitamin-C administration diminishes early postburn lipid peroxidation and reduces microvascular leakage of fluid and protein.

Effect of antioxidant vitamin supplementation on muscle function after eccentric exercise
Jakeman P.; Maxwell S.
Applied Physiology Research Unit, School Sport and Exercise Sciences, University of Birmingham, Birmingham B15 2TT United Kingdom
Eur. J. Appl. Physiol. Occup. Physiol. (Germany), 1993, 67/5 (426-430)

This study investigated the effects of antioxidant vitamin supplementation upon muscle contractile function following eccentric exercise and was performed double blind. Twenty-four physically active young subjects ingested either placebo (400 mg; n = 8), vitamin E (400 mg; n = 8) or Vitamin-C (400 mg; n = 8) for 21 days prior to and for 7 days after performing 60 min of box-stepping exercise. Contractile function of the triceps surae was assessed by the measurement of maximal voluntary contraction (MVC) and the ratio of the force generated at 20 Hz and 50 Hz tetanic stimulation before and after eccentric exercise and for 7 days during recovery. Following eccentric exercise, MVC decreased to 75 (4)% (mean (SE); n = 24; P < 0.05) of the preexercise values and the 20/50 Hz ratio of tetanic tension from 0.76 (0.01) to 0.49 (0.03) (mean (SE); n = 24; P < 0.05). Compared to the placebo group no significant changes in MVC were observed immediately post-exercise, though recovery of MVC in the first 24 h post-exercise was greater in the group supplemented with Vitamin-C. The decrease in 20/50 Hz ratio of tetanic tension was significantly less (P < 0.05) postexercise and in the initial phase of recovery in subjects supplemented with Vitamin-C but not with vitamin E. These data suggest that prior Vitamin-C supplementation may exert a protective effect against eccentric exercise-induced muscle damage.

Vitamin-C as a radioprotector against iodine-131 in vivo
Narra VR; Howell RW; Sastry KS; Rao DV
Department of Radiology, University of Medicine and Dentistry of New Jersey, Newark.
J Nucl Med 1993 Apr;34(4):637-40

The capacity of Vitamin-C (ascorbic acid) to mitigate radiation damage resulting from the tissue-incorporated radionuclide 131I is examined. Spermatogenesis in mice is the experimental model and spermhead survival is the biological endpoint. When a small nontoxic amount of Vitamin-C was injected, followed by a similar injection of 131I, the 37% spermhead survival dose (D37) increased by a factor of 2.2 compared with the D37 in animals receiving only the radionuclide. Similar radioprotection was also observed when the animals were maintained on a diet enriched with 1% vitamin C (by weight). These results suggest that Vitamin-C may play an important role as a radioprotector against accidental or medical radiation exposures, especially when radionuclides are incorporated in the body and deliver the dose in a chronic fashion.

Effects of high-dose Vitamin-C administration on postburn microvascular fluid and protein flux
Matsuda T, Tanaka H, Hanumadass M, Gayle R, Yuasa H, Abcarian H, Matsuda H, Reyes H
Burn Center, Cook County Hospital, Chicago, IL 60612.
J Burn Care Rehabil 1992 Sep-Oct;13(5):560-6

The effects of Vitamin-C treatment (14 mg/kg/hr) on burn injury were evaluated in the hind paws of 12 mongrel dogs. A lymph duct above one hind paw of each dog was cannulated. Hourly lymph flow rates (QL) and plasma and lymph total protein concentrations were measured before the burn injury and for 6 hours after the burn injury. Data from 24 paws were divided into four groups: nonburn without treatment, nonburn with treatment, burn without treatment, and burn with treatment. The nonburn groups showed no significant differences in QL or in total protein flux. In the burn groups the postburn hourly QL increased by sevenfold in the nontreatment group and only by threefold in the treatment group, whereas the postburn hourly total protein flux increased by fifteenfold and fivefold, respectively. We conclude that administration of high-dose Vitamin-C reduces early postburn microvascular leakage of fluid and protein.

Modification of the daily photoreceptor membrane shedding response in vitro by antioxidants
Williams D.S.; Roberts E.A.
Indiana University, 800 East Atwater Avenue, Bloomington, IN 47405 USA
Invest. Ophthalmol. Visual Sci. (USA), 1992, 33/10 (3005-3008)

The shedding of rod outer segment disc membrane was investigated in a commonly used frog eyecup preparation, with respect to length of time in vitro. It was found that the amplitude, but not the timing, of the 'dawn' (ie, when the lights are turned on) shedding response was increased threefold if the time in vitro was increased from 1.5-2 hr to 12-13 hr before dawn. After the overnight incubation, morphologic deterioration of the photoreceptors was not apparent by light or electron microscopy. The addition of the antioxidants, Vitamin-C or alpha-tocopherol (vitamin E), inhibited the increase in shedding, suggesting that it was induced by oxidation. These results help define conditions necessary for the maintenance of normal retinal metabolism in vitro. They also suggest a link between the amplitude of the dawn disc membrane shedding response and oxidation.

Ascorbate treatment prevents accumulation of phagosomes in RPE in light damage
Blanks J.C.; Pickford M.S.; Organisciak D.T.
Doheny Eye Institute, 1355 San Pablo Street, Los Angeles, CA 90033 USA
Invest. Ophthalmol. Visual Sci. (USA), 1992, 33/10 (2814-2821)

In dark-reared albino rats, exposure to 2 or 3 hr of intense light interrupted by 2 hr dark periods resulted in extensive degeneration of photoreceptor cells and degeneration of the retinal pigment epithelium (RPE). Ascorbate (ie, Vitamin-C) administration prior to light exposure protected photoreceptors and the RPE from light damage. In the present study, ascorbate-treated and untreated rats were exposed to various cycles of intermittent light. Immediately after this light exposure, phagosome frequency in the RPE was morphologically evaluated in comparable 50 microm sections. In untreated rats, exposure to 2 or 3 hr of intermittent light resulted in a five- to sixfold increase in phagosome density compared to unexposed controls. In contrast, no increase in phagosome density was observed in ascorbate-treated rats. In these animals, under all lighting regimens, phagosome levels remained essentially identical to those in rats not exposed to light. After a single nondamaging light exposure, phagosome density remained at the level of dark controls in ascorbate-treated and untreated rats. These results indicate that phagosome frequency may serve as an index for light damage and that the protective effect of ascorbate may be linked to its capacity to prevent rod outer segment shedding and phagocytosis under intense light conditions.

Topical Vitamin-C protects porcine skin from ultraviolet radiation-induced damage
Darr D.; Combs S.; Dunston S.; Manning T.; Pinnell S.
Box 3135, Duke University Medical Center, Durham, NC 27710 USA
Br. J. Dermatol. (United Kingdom), 1992, 127/3 (247-253)

Ultraviolet radiation damage to the skin is due, in part, to the generation of reactive oxygen species. Vitamin-C (L-ascorbic acid) functions as a biological co-factor and antioxidant due to its reducing properties. Topical application of Vitamin-C has been shown to elevate significantly cutaneous levels of this vitamin in pigs, and this correlates with protection of the skin from UVB damage as measured by erythema and sunburn cell formation. This protection is biological and due to the reducing properties of the molecule. Further, we provide evidence that the vitamin C levels of the skin can be severely depleted after UV irradiation, which would lower this organ's innate protective mechanism as well as leaving it at risk of impaired healing after photoinduced damage. In addition, Vitamin-C protects porcine skin from UVA-mediated phototoxic reactions (PUVA) and therefore shows promise as a broad-spectrum photoprotectant.

The synergism of gamma-interferon and tumor necrosis factor in whole body hyperthermia with vitamin C to control toxicity
Rosen P.
Hasbrouck Laboratory, University of Massachusetts, Amherst, MA 01003 USA
Med. Hypotheses (United Kingdom), 1992, 38/3 (257-258)

In a previous paper, the synergism of gamma-interferon and tumor necrosis factor was considered with whole body hyperthermia. Because of the toxic effect of TNF due to oxygen radicals, it is suggested that Vitamin-C be added.

Tirilazad mesylate protects vitamins C and E in brain ischemia-reperfusion injury
Sato P.H.; Hall E.D.
Department of Pharmacology, Michigan State University, East Lansing, MI 48824 USA
J. Neurochem. (USA), 1992, 58/6 (2263-2268)

Brain concentrations of the antioxidant vitamins C and E decreased following unilateral carotid occlusion and reperfusion for 2 or 24 h in gerbils. Administration of the 21-aminosteroid inhibitor of lipid peroxidation, tirilazad mesylate (U74006F), prevented the decrease in level of both of these vitamins following 2 h of reperfusion. After 24 h of reperfusion, however, alpha-tocopherol (vitamin E) continued to be protected, but ascorbic acid (vitamin C) showed a pronounced decrease in content. The changes in concentrations of these vitamins are consistent with U74006F acting to inhibit peroxidation in the CNS by scavenging of lipid peroxyl radicals and suggest that, in the presence of this agent, injury-induced depletion of ascorbic acid may occur without irreversible tissue damage.

Vitamin-C supplementation in the patient with burns and renal failure
Dylewski DF, Froman DM
Parenteral Nutrition Support Service, Francis Scott Key Medical Center, Baltimore, MD.
J. Burn Care Rehabil. (USA), 1992, 13/3 (378-380)

Vitamin-C supplementation is an important component of nutritional management in patients with burns. To supply appropriate vitamin C therapy, complications such as renal failure must be considered. An understanding of current vitamin regimens and potential metabolic sequelae can assist the practitioner in providing safe and therapeutic Vitamin-C doses.

High-dose Vitamin-C therapy for extensive deep dermal burns
Matsuda T.; Tanaka H.; Shimazaki S.; Matsuda H.; Abcarian H.; Reyes H.; Hanumadass M.
Burn Center, Cook County Hospital, 700 S. Wood Street, Chicago, IL 60612 USA
USA Burns (United Kingdom), 1992, 18/2 (127-131)

We studied the haemodynamic effects of antioxidant therapy with high-dose Vitamin-C administration (170 mg/kg/24h) in guinea-pigs with 70 per cent body surface area deep dermal burns. The animals were divided into three groups of six animals each. Group 1 was resuscitated with Ringer's lactate solution according to the Parkland formula; group 2 with 25 per cent of the Parkland formula with Vitamin-C; and group 3 with 25 per cent of the Parkland formula without Vitamin-C. There were no significant differences in heart rates or in blood pressures between the groups throughout the 24-h study period. Group 3 showed significantly higher haematocrit values at 3 h postburn and thereafter as compared with those of group 2. The cardiac output values of group 2 were significantly higher than those of group 3, but equivalent to those of group 1. The water content of the burned skin in group 2 was significantly lower than that in the other groups, indicating that increased postburn capillary permeability was minimized by the administration of Vitamin-C. With adjuvant high-dose Vitamin-C administration, we were able to reduce the 24-h resuscitation fluid volume from 4 ml/kg/per cent burn to 1 ml/kg/per cent burn, while maintaining adequate cardiac output.

Metabolic and immune effects of enteral ascorbic acid after burn trauma
Nelson J.L.; Alexander J.W.; Jacobs P.A.; Ing R.D.; Ogle C.K.
Shriners Burns Institute, 202 Goodman Street, Cincinnati, OH 45219 USA
Burns (United Kingdom), 1992, 18/2 (92-97)

A burned guinea-pig model (30 per cent BSA) was used to study the effect of Vitamin-C on immune and metabolic responses following burn trauma. Thirty-six guinea-pigs received identical enteral diets (175 kcal/kg) except for the amount of Vitamin-C. Groups I, II, III and IV were given formulae delivering no Vitamin-C (1 RDA) 15 mg/kg/day 75 mg/kg/day or 375 mg/kg/day respectively. Resistance to infection was evaluated by injecting each animal with 0.1 ml of 1 x 109 Staph. aureus 502A subcutaneously on day 10. On day 14, Staph. aureus abscesses were excised and the numbers of viable colonies were determined. Results showed no statistical differences between groups in the clearance of Staph. aureus. From days 2 to 12, animals in groups I, II and III had body weights of approximately 97 per cent of preburn body weight. Animals in group IV however, had a body weight gain, 102 per cent of preburn body weight on day 12. Animals in group IV also had significantly lower metabolic rates on day 12 as compared to the animals in the other groups. These results suggest that large amounts of Vitamin-C have beneficial effects on the maintenance of body weight and metabolic rate following burn trauma.

Reduced fluid volume requirement for resuscitation of third-degree burns with high-dose Vitamin-C
Matsuda T.; Tanaka H.; Williams S.; Hanumadass M.; Abcarian H.; Reyes H.
Burn Center, Cook County Hospital, 700 S. Wood St., Chicago, IL 60612 USA
J. Burn Care Rehabil. (USA), 1991, 12/6 (525-532)

The effects of high-dose Vitamin-C therapy (170 mg, 340 mg, and 680 mg/kg/day) were evaluated in 70% body surface area third-degree burns in guinea pigs that were resuscitated with 1 ml/kg/%burn Ringer's lactate solution. The water content measurements of the burned skin at 24 hours after burn injury in the Vitamin-C-treated groups were significantly lower than those of the control group (1 ml/kg/%burn) and those of the standard resuscitation group (4 ml/kg/%burn). The cardiac outputs in the group that received 340 mg Vitamin-C were significantly higher than those of the control group but not significantly different than those of the standard therapy group at 2 hours after burn injury and thereafter. In comparison with the regimen of 340 mg Vitamin-C, the regimen of 680 mg Vitamin-C was no more beneficial, and the regimen of 170 mg was less effective. With administration of adjuvant high-dose Vitamin-C, we were able to reduce the total 24-hour resuscitation volume from 4 ml/kg/%burn to 1 ml/kg/%burn, while a comparable cardiac output was maintained.

Biochemical basis of ozone toxicity
Mustafa M.G.
Department of Environmental Health Sciences, University of California, School of Public Health, Los Angeles, CA 90024 USA
Free Radic. Biol. Med. (USA), 1990, 9/3 (245-265)

Ozone (O3) is the major oxidant of photochemical smog. Its biological effect is attributed to its ability to cause oxidation or peroxidation of biomolecules directly and/or via free radical reactions. A sequence of events may include lipid peroxidation and loss of functional groups of enzymes, alteration of membrane permeability, and cell injury or death. An acute exposure to O3 causes lung injury involving the ciliated cell in the airways and the type 1 epithelial cell in the alveolar region. The effects are particularly localized at the junction of terminal bronchioles and alveolar ducts, as evident from a loss of cells and accumulation of inflammatory cells. In a typical short-term exposure the lung tissue response is biphasic: an initial injury-phase characterized by cell damage and loss of enzyme activities, followed by a repair-phase associated with increased metabolic activities, which coincide with a proliferation of metabolically active cells, for example, the alveolar type 2 cells and the bronchiolar Clara cells. A chronic exposure to O3 can cause or exacerbate lung diseases, including perhaps an increased lung tumor incidence in susceptible animal models. Ozone exposure also causes extrapulmonary effects involving the blood, spleen, central nervous system, and other organs. A combination of O3 and NO2, both of which occur in photochemical smog, can produce effects which may be additive or synergistic. A synergistic lung injury occurs possibly due to a formation of more powerful radicals and chemical intermediates. Dietary antioxidants, for example, vitamin E, Vitamin-C, and selenium, can offer a protection against O3 effects.

Decreases in tissue levels of ubiquinol-9 and -10, ascorbate and alpha-tocopherol following spinal cord impact trauma in rats
Lemke M.; Frei B.; Ames B.N.; Faden A.I.
Center for Neural Injury, Department of Neurology, University of California, San Francisco, CA USA
USA Neurosci. Lett. (Netherlands), 1990, 108/1-2 (201-206)

Generation of free radicals and subsequent lipid peroxidation have been proposed to contribute to delayed tissue damage following traumatic spinal cord injury (SCI). Ubiquinols (reduced coenzyme Q), ascorbate (Vitamin-C), and alpha-tocopherol (vitamin E) are endogenous antioxidants; decreases in tissue levels of these compounds may, therefore, reflect ongoing oxidative reactions. In the present studies, alterations in tissue levels of ubiquinol-9 and -10, ascorbate, and alpha-tocopherol were examined after SCI of varying severity in the rat. Levels of alpha-tocopherol did not change significantly after injury. Ascorbate and ubiquinol levels were decreased after trauma. Changes in tissue levels of ubiquinol, but not ascorbate reflected the degree of trauma. Thus, ubiquinol levels may provide a useful marker of the oxidative component of the secondary injury response.

Nutritional considerations for the burned patient
Pasulka P.S.; Wachtel T.L.
Burn and Trauma Service, Good Samaritan Medical Center, Phoenix, AZ 85006 USA
Surg. Clin. North Am. (USA), 1987, 67/2 (109-131)

The metabolic response to injury is one of marked catabolic hormonal predominance resulting in hypermetabolism and protein wasting. Energy expenditure increases with increasing severity of injury, but reaches a maximum of twice resting energy expenditure when 50 percent TBSA is burned. We agree with the nutritional recommendations of the group at the Boston Shriner's Burn Institute and the Massachusetts General Hospital. These include providing calories at twice the resting energy expenditure, as predicted by the Harris-Benedict equations, for patients with greater than 30 percent BSAB; protein is provided at 2.5 gm per kg per day based on ideal body weight. It is important to recognize that these are optimal goals, but their attainment must be governed by safety considerations for the patient. It is probably safe to supplement intake with a multivitamin and Vitamin-C, as well as zinc, but our understanding of micronutrient therapy for stressed patients is rudimentary.

Ascorbic acid metabolism in trauma
Mukherjee D.; Som S.; Chatterjee I.B.
Dep. Biochem., Univ. Coll. Sci., Calcutta 700019 India
Indian J. Med. Res. (India), 1982, 75/5 (748-751)

In major trauma such as severe head injury, burns or lacerated injury, there was a precipitous fall in plasma ascorbic acid level accompanied by a significant rise in blood dehydroascorbate level. However, this change was temporary and normal Vitamin-C status was regained after recovery from the stress condition. A similar alteration in plasma ascorbate level was also found after major surgery. This alteration in ascorbic acid status was not due to lack of reduction of dehydroascorbic acid to ascorbic acid but due to a high turnover of ascorbic acid in trauma. Supplementation of ascorbic acid in trauma resulted in a temporary increase in the plasma ascorbic acid level.

Multiple pathologic fractures in osteogenesis imperfecta
Gerber B.E.; Jani L.
Orthop. Klin., Chir. Dept., Univ. Basel, 4055 Basel Switzerland
Orthopade (Germany, West), 1982, 11/3 (101-108)

The authors survey the current orthopedic possibilities in treating multiple fractures in osteogenesis imperfecta. Also the general influence of Vitamin-C treatment is discussed.

Effect of zinc supplementation in fracture healing
Chaturvedi S.N.; Singh K.N.; Shukla R.K.; Singh R.K.
Dept. Orthop. Surg., G.S.V.M. Med. Coll., Kanpur India
Indian J. Orthop. (India), 1980, 14/1 (62-71)

In the present experimental study, 36 rabbits were subjected to fracture of the of the fibula and were treated in 3 groups viz., Control group, Zinc sulphate supplemented group and Zinc sulphate vit. C. + Methandienone supplemented group. Each group consisted of 12 rabbits. After roentgenological, macroscopic and histological examination of healing of fractures of weekly intervals, it was concluded that the Zinc supplementation to an appreciable extent enhanced the process of bone healing which could be further hastened by addition of Vitamin-C and Dianabol. No significant toxic or side effect of zinc supplementation was observed in any of the rabbits. A clinical trial of the same drugs was also conducted in patients with fractures of the shaft of the femur.

Treatment results of spinal cord injuries in the Swiss paraplegic centre of Basle
Zaech G.A.; Seiler W.; Dollfus P.
Swiss Paraplegic Cent., Basle Switzerland
Paraplegia (Edinb.) (Scotland), 1976, 14/1 (58-65)

The results concerning the last 117 acute traumatic spinal cord lesions admitted in the Swiss Paraplegic Centre of Basle have been analysed as regards the rate of neurological recovery. The treatment not only concerns the vertebral damage but also the medical aspects of the spinal cord lesion itself. The routine use of combined Dexamethasone, Rheomacrodex and Hydergine in the very early treatment might have accounted for encouraging results which need to be confirmed in the future.

Effect of piracetam on electroshock induced amnesia and decrease in brain acetylcholine in rats
Bhattacharya S.K.; Upadhyay S.N.; Jaiswal A.K.
Department of Pharmacology, Institute of Medical Sciences, Banaras Hindu University, Varanasi 221 005 India
Indian J. Exp. Biol. (India), 1993, 31/10 (822-824)

Piracetam, a prototype of a new class of psychotropic agents, the nootropic agents, which improve learning ability and memory retention, was found to induce a dose-related prevention of disruption of acquisition of a passive avoidance response produced by electroshock application. The amnesia attenuating effect of piracetam was accompanied by prevention of the decrease in acetylcholine concentrations of rat brain induced by electroshock. The study indicates that the cognition enhancing effect of piracetam may be due to a facilitatory effect on cholinergic transmission.

Use of piracetam in treatment of head injuries. Observations in 903 cases.
Cicerchia G.; Santucci R.; Palmieri M.
Ospedale della Misericordia, Servizio di Pronto Soccorso, Area di Degenza per l'Emergenza, Grosseto Italy
Clin. Ter. (Italy), 1985, 114/6 (481-487)

The authors report on 903 patients with head concussion of varying degrees of severity who were treated with anti-oedema drugs associated with an activator of cerebral metabolism. This treatment resulted in a swift disappearance of symptoms and in a quick recovery of normal cerebral activity, and moreover in a noticeable decrease of the time of hospitalisation.

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