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The aim of this study is testing black grape juice as a radiomodifier against whole body X-irradiation using an animal model. Sixteen male Wistar rats were divided into four groups where two were irradiated by X-rays from a 200 kV machine specially designed to biological samples. Animals were fed ad libitum and drank voluntarily 2-10 ml a day of grape juice or placebo (isocaloric glucose and fructose solution) for one week before and two weeks after 6 Gy X-irradiation when they were sacrificed. Results have shown a significant liver weight loss in irradiated placebo group only while grape juice one has presented no losses. Hematological analysis showed typical abnormalities for ionizing radiation exposure, including early leucopenia and anemia. The intake of grape juice induced an increase in granulocyte percent count. [ABSTRACT FROM AUTHOR]

There is limited evidence of phenolic compounds acting as protective agents on several cancer types, including breast cancer (BC). Nevertheless, some polyphenol classes have not been investigated and there is a lack of studies assessing the effect on menopausal status and hormone receptor status as influenced by these compounds. The objective of this study is to evaluate the association between the intake of all polyphenol classes in relation to the BC risk by menopausal and hormone receptor status. We used data from a population-based multi-case-control study (MCC-Spain) including 1472 BC cases and 1577 controls from 12 different regions of Spain. The odds ratios (ORs) with 95% CI were calculated using logistic regression of mixed effects by quartiles and log2 of polyphenol intakes (adjusted for the residual method) of overall BC, menopausal and receptor status. No associations were found between total intake of polyphenols and BC risk. However, inverse associations were found between stilbenes and all BC risk (OR Q4 vs. Q1 : 0.70, 95%CI: 0.56-0.89, P trend = 0.001), the consumption of hydroxybenzaldehydes (OR Q4 vs. Q1 : 0.75, 95%CI: 0.59-0.93, P trend = 0.012) and hydroxycoumarins (OR Q4 vs. Q1 : 0.73, 95%CI: 0.57-0.93; P trend = 0.005) were also inversely associated. The intake of stilbenes, hydroxybenzaldehydes and hydroxycoumarins can contribute to BC reduction risk on all menopausal and receptor statuses.

Purpose: Although there is convincing evidence that red and processed meat intake increases the risk of colorectal cancer (CRC), the potential role of meat cooking practices has not been established yet and could partly explain the current heterogeneity of results among studies. Therefore, we aimed to investigate the association between meat consumption and cooking practices and the risk of CRC in a population-based case-control study., Methods: A total of 1671 CRC cases and 3095 controls recruited in Spain between September 2008 and December 2013 completing a food frequency questionnaire with a meat-specific module were included in the analyses. Odds ratios (OR) and confidence intervals (CI) were estimated by logistic regression models adjusted for known confounders., Results: Total meat intake was associated with increased risk of CRC (OR T3-T1 1.41; 95% CI 1.19-1.67; p trend  < 0.001), and similar associations were found for white, red and processed/cured/organ meat. Rare-cooked meat preference was associated with low risk of CRC in red meat (OR rare vs. medium 0.66; 95% CI 0.51-0.85) and total meat (OR rare vs. medium 0.56; 95% CI 0.37-0.86) consumers, these associations being stronger in women than in men. Griddle-grilled/barbecued meat was associated with an increased CRC risk (total meat: OR 1.45; 95% CI 1.13-1.87). Stewing (OR 1.25; 95% CI 1.04-1.51) and oven-baking (OR 1.18; 95% CI 1.00-1.40) were associated with increased CRC risk of white, but not red, meat., Conclusions: Our study supports an association of white, red, processed/cured/organ and total meat intake with an increased risk of CRC. Moreover, our study showed that cooking practices can modulate such risk.

Purpose: Whole brain irradiation (WBI) causes a variety of secondary side-effects including anorexia and bone necrosis. We evaluated the radiomodifying effect of black grape juice (BGJ) on WBI alterations in rats measuring food and water intake, body weight, hemogram, and morphological and histological mandibular parameters., Materials and Methods: Forty male rats (200-250 g) were exposed to eight sessions of cranial X-ray irradiation. The total dose absorbed was 32 Gy delivered over 2 weeks. Four groups were defined: (i) NG: non-irradiated, glucose and fructose solution-supplemented (GFS); (ii) NJ: non-irradiated, BGJ-supplemented; (iii) RG: irradiated, GFS-supplemented; and (iv) RJ: irradiated, BGJ-supplemented. Rats received daily BGJ or GFS dosing by gavage starting 4 days before, continuing during, and ending 4 days after WBI., Results: RJ rats ingested more food and water and showed less body weight loss than RG rats during the irradiation period. Forty days after WBI, irradiated animals started losing weight again compared with controls as a consequence of masticatory hypofunction by mandibular osteoradionecrosis (ORN). Osteoclastic activity and inflammation were apparent in RG rat mandibles. BGJ was able to attenuate the severity of ORN as well as to improve white and red blood cell counts., Conclusions: Fractionated whole brain irradiation induces mandibular changes that interfere with normal feeding. BGJ can be used to mitigate systemic side-effects of brain irradiation and ORN.

Background: Ingested nitrate leads to endogenous formation of N-nitroso compounds that are breast carcinogens in animals, but human evidence is limited., Objective: We evaluated ingested nitrate as a risk factor for breast cancer (BC) in a multicase-control study., Methods: Hospital-based incident BC cases and population-based controls were recruited in eight Spanish regions in 2008-2013; participants provided residential and water consumption from 18 years of age and information on known BC risk factors. Long-term nitrate levels (1940-2010) were estimated and linked with residential histories and water consumption to calculate waterborne ingested nitrate (milligrams/day). Dietary ingested nitrate (milligrams/day) was calculated using food frequency questionnaires and published dietary nitrate contents. Interactions with endogenous nitrosation factors and other variables were evaluated. A total of 1,245 cases and 1,520 controls were included in the statistical analysis., Results: Among the study regions, average ± SD waterborne ingested nitrate ranged from 2.9 ± 1.9 to 13.5 ± 7.5 mg/day, and dietary ingested nitrate ranged from 88.5 ± 48.7 to 154 ± 87.8 mg/day. Waterborne ingested nitrate was not associated with BC overall, but among postmenopausal women, those with both high nitrate (> 6 vs. < 2.6 mg/day) and high red meat intake (≥ 20 vs. < 20 g/day) were more likely to be cases than women with low nitrate and low red meat intake (adjusted odds ratio = 1.64; 95% confidence interval: 1.08, 2.49; overall interaction p-value = 0.17). No association was found with dietary nitrate., Conclusions: Waterborne ingested nitrate was associated with BC only among postmenopausal women with high red meat consumption. Dietary nitrate was not associated with BC regardless of the animal or vegetable source or of menopausal status., Citation: Espejo-Herrera N, Gracia-Lavedan E, Pollan M, Aragonés N, Boldo E, Perez-Gomez B, Altzibar JM, Amiano P, Zabala AJ, Ardanaz E, Guevara M, Molina AJ, Barrio JP, Gómez-Acebo I, Tardón A, Peiró R, Chirlaque MD, Palau M, Muñoz M, Font-Ribera L, Castaño-Vinyals G, Kogevinas M, Villanueva CM. 2016. Ingested nitrate and breast cancer in the Spanish Multicase-Control Study on Cancer (MCC-Spain). Environ Health Perspect 124:1042-1049; http://dx.doi.org/10.1289/ehp.1510334.

Background: Accumulated exposure to hormones and growth factors during early life may influence the future risk of breast cancer (BC). This study examines the influence of childhood-related, socio-demographic and anthropometric variables on BC risk, overall and by specific pathologic subtypes., Methods: This is a case-control study where 1539 histologically-confirmed BC cases (23-85 years) and 1621 population controls, frequency matched by age, were recruited in 10 Spanish provinces. Perinatal and childhood-related characteristics were directly surveyed by trained staff. The association with BC risk, globally and according to menopausal status and pathologic subtypes, was evaluated using logistic and multinomial regression models, adjusting for tumor specific risk factors., Results: Birth characteristics were not related with BC risk. However, women with high socioeconomic level at birth presented a decreased BC risk (OR=0.45; 95% CI=0.29-0.70), while those whose mothers were aged over 39 years at their birth showed an almost significant excess risk of hormone receptor positive tumors (HR+) (OR=1.35; 95% CI=0.99-1.84). Women who were taller than their girl mates before puberty showed increased postmenopausal BC risk (OR=1.26; 95% CI=1.03-1.54) and increased HR+ BC risk (OR=1.26; 95% CI=1.04-1.52). Regarding prepubertal weight, while those women who were thinner than average showed higher postmenopausal BC risk (OR=1.46; 95% CI=1.20-1.78), associated with HR+ tumors (OR=1.34; 95% CI=1.12-1.61) and with triple negative tumors (OR=1.56; 95% CI=1.03-2.35), those who were heavier than average presented lower premenopausal BC risk (OR=0.64; 95% CI=0.46-0.90) and lower risk of epidermal growth factor receptor positive tumors (OR=0.61; 95% CI=0.40-0.93)., Conclusion: These data reflect the importance of hormones and growth factors in the early stages of life, when the mammary gland is in development and therefore more vulnerable to proliferative stimuli., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Whole-body irradiation has been associated with liver function alterations. Ionizing radiation exposure increases oxidative stress and antioxidants can activate transcription of antioxidant target genes. In the present study, modifications of the liver antioxidant system were evaluated at 7 and 30 days following sub-lethal whole-body X-irradiation in male Wistar rats, which were intragastrically supplemented with quercetin or control solvent for 4 days prior to and 6 days following irradiation. Animal groups were as follows: CS, control, solvent-supplemented; CQ, control, quercetin-supplemented; RS, irradiated, solvent-supplemented; and RQ, irradiated, quercetin-supplemented. After 7 days, liver tissue from RS animals demonstrated marked hydropic panlobular degeneration with Mallory bodies in ballooning hepatocytes. These changes were mostly reversed in RQ rats. Lipid peroxidation in addition to copper/zinc superoxide dismutase (Cu/Zn-SOD), nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and Kelch-like ECH-associated protein 1 (Keap1) protein expression levels were all increased by X-irradiation, but significantly decreased by quercetin supplementation. Catalase (CAT) and, Nad(p)h: quinone oxidoreductase 1 (NQO1) expression levels remained high in irradiated rats regardless of quercetin supplementation. After 30 days, the liver from RS animals had small portal infiltrates and diffuse cytoplasmic vacuolization, with reduced lipid peroxidation and reduced expression levels of CAT, NQO1, Nrf2 and Keap1, but consistently elevated Cu/Zn-SOD expression. RQ animals indicated reduced expression levels of Nrf2 and Keap1 30 days after irradiation. The present study demonstrated a quercetin-induced reduction of the oxidative stress-associated increase in Nrf2 expression that may be useful for preventing cancer cell survival in response to ionizing radiation exposure.

The aim of this work was to test the hypothesis that a moderate intake of organic purple grape juice shows a positive radiomodifier effect over early behavioural damage following acute X-irradiation in mice. Anxiety-, locomotion-, and feeding-related responses to 6 Gy total body X-irradiation (TBI) were studied via open field, Rotarod, and feeding/drinking recording. Thirty-two male mice weighing 25-30 g were grouped according grape juice (J) or water (W) ad libitum drinking and either non-irradiated (N) or irradiated (R). 24 h post-TBI the access frequency to the center and corners of the open field was decreased, and the total stay in the corners increased, in RW vs. NW mice. Anxiety-related parameters decreased in RJ vs. RW mice. Rotarod latency times increased 72 h post-TBI in RJ vs RW mice. No overall changes in food and drink intake were observed along the experimental period. On the irradiation day, bout number was increased and bout duration was decreased in RW mice. The changes were reversed by purple grape juice intake. Grape juice intake before and after TBI can overcome several radiation-induced changes in behaviour within 24-72 hours after sub-lethal X-irradiation. This beneficial effect on short-term anxiety and mobilityrelated activities could probably be included in the list of flavonoid bio-effects. The present findings could be relevant in designing preventive interventions aimed to enhance body defense mechanisms against short-term irradiation damage., (Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.)

The feasibility of treating the supernatant of a municipal sludge digester supplemented with co-substrates by means of an anammox-based process (ELAN(®)) was tested in Guillarei (NW of Spain). Ammonia concentration measured in the supernatant of the sludge digester varied in the range 800-1,500 g N/m(3) due to the fact that the sludge produced in the plant was co-digested with wastes coming from surrounding food industries. Treating this supernatant in the ELAN(®) reactor, nitrogen removal rates up to 1.1 kg N/(m(3) d) were reached in experiments run in a pilot plant reactor operated in batch mode. No nitrite oxidation was registered after several months of operation despite the average dissolved oxygen (DO) concentrations being 1.5 g O2/m(3) and the temperature reaching values as low as 18 °C. By keeping the DO set point at 1-2 g O2/m(3) and tuning the hydraulic retention time, the stability of the process was guaranteed and the presence of co-substrates in the anaerobic digester did not affect negatively the operation of the autotrophic nitrogen removal process. Due to the success of the pilot plant experiment, an upscale of the process to full scale is proposed. Mass balances applied to Guillarei wastewater treatment plant revealed that in the main stream line the average denitrification rate calculated with the data of year 2011 was 226 kg N/d. Since the nitrogen removal efficiency is limited by the amount of readily biodegradable organic matter available to carry out denitrification in the water line, the implementation of an anammox-based process to treat the supernatant seems the best option to improve the effluent quality in terms of nitrogen content. The nitrogen removal rate in the sludge line would be 30 times higher than the one in the water line. The implementation of the process would improve the energetic balance and the nitrogen removal performance of the plant.

The aim of this study was to evaluate the potential positive effect of black grape juice (BGJ) on lipid peroxidation considering Total Body Irradiation (TBI) in Wistar rats. As a potential feasible means of evaluation in situ, blood serum lactate dehydrogenase (LDH) levels were evaluated as a marker for heart damage from acute radiation syndrome (ARS). Twenty rats were divided into four groups, two of them being irradiated by gamma-rays from a Co-60 source. Animals were treated by gavage with 2 mL per day of BGJ or placebo for one week before and 4 days after 6 Gy whole body gamma-irradiation, when they were euthanasiated. LDH on serum and lipid peroxidation on heart tissue were evaluated. High concentration of metabolites from lipid peroxidation in heart, and high LDH level on serum were found only in gamma-irradiated group given placebo, mainly at the first 24 h after radiation. Phytochemical analysis of BGJ was performed by determining total phenolics, flavonoids, and tannins followed by a high-performance liquid chromatography (HPLC/DAD) analysis, which showed resveratrol as the major constituent. Results suggest that BGJ is a good protective candidate compound against heart damage from ARS and its effects suggest its use as a radiomodifier.

Obesity is considered a chronic low-grade inflammatory state associated with a chronic oxidative stress caused by superoxide production (O(2)(-)). The superoxide dismutase manganese dependent (SOD2) catalyzes O(2)(-) in H(2)O(2) into mitochondria and is encoded by a single gene that presents a common polymorphism that results in the replacement of alanine (A) with a valine (V) in the 16 codon. This polymorphism has been implicated in a decreased efficiency of SOD2 transport into targeted mitochondria in V allele carriers. Previous studies described an association between VV genotype and metabolic diseases, including obesity and diabetes. However, the causal mechanisms to explain this association need to be more elucidated. We postulated that the polymorphism could influence the inflammatory response. To test our hypothesis, we evaluated the in vitro cytokines production by human peripheral blood mononuclear cells (PBMCs) carrier's different Ala16Val-SOD2 genotypes (IL-1, IL-6, IL-10, TNF-α, IFN-γ). Additionally, we evaluated if the culture medium glucose, enriched insulin, could influence the cytokine production. Higher levels of proinflammatory cytokines were observed in VV-PBMCs when compared to AA-PBMCs. However, the culture medium glucose and enriched insulin did not affect cytokine production. The results suggest that Ala16Val-SOD2 gene polymorphism could trigger the PBMCs proinflammatory cytokines level. However, discerning if a similar mechanism occurs in fat cells is an open question., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Meals have long been considered relevant units of feeding behavior. Large data sets of feeding behavior of cattle, pigs, chickens, ducks, turkeys, dolphins, and rats were analyzed with the aims of 1) describing the temporal structure of feeding behavior and 2) developing appropriate methods for estimating meal criteria. Longer (between-meal) intervals were never distributed as the negative exponential assumed by traditional methods, such as log-survivorship analysis, but as a skewed Gaussian, which can be (almost) normalized by log-transformation of interval lengths. Log-transformation can also normalize frequency distributions of within-meal intervals. Meal criteria, i.e., the longest interval considered to occur within meals, can be estimated after fitting models consisting of Gaussian functions alone or of one Weibull and one or more Gaussian functions to the distribution of log-transformed interval lengths. Nonuniform data sets may require disaggregation before this can be achieved. Observations from all species were in conflict with assumptions of random behavior that underlie traditional methods for criteria estimation. Instead, the observed structure of feeding behavior is consistent with 1) a decrease in satiety associated with an increase in the probability of animals starting a meal with time since the last meal and 2) an increase in satiation associated with an increase in the probability of animals ending a meal with the amount of food already consumed. The novel methodology proposed here will avoid biased conclusions from analyses of feeding behavior associated with previous methods and, as demonstrated, can be applied across a range of species to address questions relevant to the control of food intake.

Celiac disease is characterised by chronic immune-mediated malabsorption in genetically susceptible individuals induced by gluten proteins present in wheat, barley and rye. It occurs in adults and children at rates approaching 1% of the population. Cardiomyopathy associated with celiac disease is infrequent. The authors present here a first case of a severe progressive dilated cardiomyopathy that required heart transplantation in young woman with celiac disease.

Aims: The aim of this study was to evaluate the potential protective effects of ad libitum black grape (Vitis labrusca) juice against liver oxidative damage in whole-body acute X-irradiated rats., Main Methods: Animals were fed ad libitum and drank voluntarily black grape juice or placebo (isocaloric glucose and fructose solution) for 6 days before and 15 days following a 6 Gy X-irradiation from a 200 kV machine., Key Findings: Irradiated animals receiving placebo showed a significant increase in the concentration of thiobarbituric acid-reactive substances (TBARS), a marker of lipid peroxidation, as well as a significant decrease in both Cu/Zn superoxide dismutase (Cu/ZnSOD) and glutathione peroxidase (GPx) activity and reduced glutathione concentration (GSH). Black grape juice supplementation resulted in a reversal of lipid peroxidation, Cu/ZnSOD activity, and GSH concentration, towards values not significantly differing from those in non-irradiated, placebo-supplemented rats. Poly(ADP-ribose) polymerase (PARP-1) and Cu/ZnSOD changes in protein expression were observed for irradiated rats. No change in p53 expression or DNA fragmentation was found., Significance: Ad libitum black grape juice intake is able to restore the liver primary antioxidant system against adverse effects due to whole-body acute X-irradiation in rats after 15 days post-irradiation. The results support using antioxidant supplements as a preventive tool against radiation-induced harm., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

The effect of orally supplemented melatonin (MT) at 1 mg/kg bw for 4 weeks on feeding behavior of non-diabetic and diabetic male Wistar rats has been studied by computerized meal pattern analysis. Exogenous MT has a satiating effect in non-diabetic rats, but not in diabetic animals. The changes in feeding behavior induced by MT in non-diabetic animals are related to changes in meal frequency, size and duration leading to lower total food intake during the scotophase. MT administration to diabetic rats resulted in lower drinking time and higher faecal output, without further behavioral effects. We conclude that the notorious metabolic changes occurring in the streptozotocin-diabetic rat can overcome most of the underlying effects of MT supplementation. The possible MT usage for therapeutical purposes could benefit from the lack of behavioral alterations in diabetic animals.

In close quarters: When confined in a metal-organic framework, magnesium borohydride reacts with arenes by a hydroboration pathway (see scheme), in contrast to its reactivity under analogous homogeneous solution-phase conditions. Framework-imposed organization of the reactive groups is required, which is achieved by a combination of the metal coordination and two hydrogen bonds.

Post-synthetic derivatisation of a porous material produces a functionalized material that binds the metal complex V(O)acac2, in contrast to the unfunctionalized precursor, which is inactive for complex binding.

Protonation of chiral porous materials introduces a Brønsted acid centre, the structure of which is unique to the heterogeneous phase requiring pore wall confinement for stable isolation.

The objective of this study was to determine in a rat model of hepatocarcinoma (HCC) the effects of the antiangiogenic agent TNP-470 on antioxidant enzymes, including catalase (CAT), superoxide dismutases (Mn-SOD and Cu,Zn-SOD), and glutathione peroxidase (GPx). Tumor was induced in male Wistar rats by diethylnitrosamine and promoted by two-thirds hepatectomy plus acetaminofluorene administration. Experiments were carried out 28 weeks after initiating the treatment. TNP-470 was administered at 30 mg/kg, 2 times per week from weeks 20 to 28. Carcinomatous tissue was growing outside dysplastic nodules in rats with HCC. HCC caused oxidative stress demonstrated by increased lipid peroxidation and oxidized/reduced glutathione ratio that was accompanied by a reduced activity of antioxidant enzymes Cu,Zn-SOD, GPx, and CAT. In contrast, Mn-SOD activity and expression were higher in hepatocarcinoma than in control groups. These effects were absent in animals receiving TNP-470. No significant differences between untreated and TNP-470-treated rats were observed in the expression of the Cu,Zn-SOD, glutathione peroxidise, and CAT. We conclude that TNP-470 inhibits expression and activity of Mn-SOD induced by experimental hepatocarcinogenesis. Oxidative stress reduction by TNP-470 accounts for yet another anti-cancer effect of this molecule.

We examined the effect of daily melatonin supplementation on liver apoptosis induced by aging in rats. Young (3-month-old) and aged (24-month-old) Wistar rats were supplemented daily with melatonin in their drinking water (20 mg/L) for 4 weeks. Aged rats showed increases in the liver concentration of thiobarbituric acid-reactive substances and in the oxidized/reduced glutathione ratio. These increases were accompanied by apoptotic ultrastructural alterations and increases in cytochrome c mitochondrial release, Bax to Bcl-2 relative expression, and activity of caspase-3. No significant changes were observed in Fas-ligand (Fas-L) expression and caspase-8 activity. Melatonin administration was able to abrogate changes detected in aged rats. Data suggest that liver apoptotic cell death is induced by reactive oxygen species, via the intrinsic signalling pathway, and that the antiapoptotic action provided by melatonin is related to its antioxidant effect, with reduction of cytochrome c release by the modulation of Bcl-2 and Bax genes.

This study compared the effects of melatonin supplementation on markers of oxidative stress, and on the activity and expression of antioxidant enzymes in the liver of young (3-month-old) and aging (24-month-old) rats. Animals were supplemented with melatonin in the drinking water (20 mg/L) for 4 wk. Liver concentration of thiobarbituric-reactive substances (TBARS), as an index of lipid peroxidation, and the oxidized to reduced glutathione ratio significantly increased in aged rats (+58%), while values did not significantly differ from the young in aged animals receiving melatonin. Significant decreases in the liver activities of Cu,Zn-superoxide dismutase (SOD) (-25%), cytosolic (-21%) and mitochondrial (-40%) glutathione peroxidase (GPx), and catalase (CAT) (-34%) were found in aged rats. Melatonin abolished these changes and also prevented the reduction of Cu,Zn-SOD (-33%), cytosolic GPx (-30%), and mitochondrial GPx (-47%) liver protein content as measured by Western blot. Reductions in Cu,Zn-SOD mRNA (-39%), and GPx mRNA (-86%) levels induced by aging were also abolished by melatonin. In summary, our data indicate that melatonin treatment abrogates oxidative stress in the liver of aged rats, and that prevention of the decreased activity of CAT and the downregulation of Cu,Zn-SOD and GPx gene expression contribute to this effect.

This review addresses the pathophysiology and treatment of hemorrhagic shock, a condition produced by rapid and significant loss of intravascular volume. Hemorrhagic shock may lead sequentially to hemodynamic instability, decreases in oxygen delivery, decreased tissue perfusion and cellular hypoxia. Multiple organ failure, a systemic inflammatory process that leads to dysfunction of different vital organs, is a frequent complication after hemorrhagic shock and accounts for a high incidence of mortality. The pathogenesis of organ injury secondary to hypovolemic insults is still not completely understood, but both experimental studies and clinical observations indicate that macrophages are activated by translocated endotoxin-bacteria and ischemia/reperfusion. Activated Kupffer cells release pathologically active substances such as inflammatory cytokines, reactive oxygen species, and nitric oxide, all of which may participate in the mechanisms of hemorrhagic shock. Moreover, increased free radical production during hemorrhagic shock and resuscitation gives place to an increase in oxidative stress that would contribute to the organ damage. In the last few years, a number of experiments have been performed in an attempt to understand the pathophysiology and treatment of hemorrhagic shock. Different studies have shown positive effects on hemorrhagic shock treatment by antioxidant, amino acid, and lipid administration.

The purpose of this study was to determine the effects of experimental fasciolosis at various stages of development on the daily food intake of sheep. Five male Churra sheep, 4 months of age, were infected orally with 300 Fasciola hepatica metacercariae over a 30 day period. There was a significant increase in serum glutamate dehydrogenase (GLDH) activity from 40 days post-infection and in aspartate aminotransferase (AST) activity from 60 days post-infection. Both enzyme activities reached maximum levels in the serum of infected animals at 80 days and then progressively decreased. Serum gamma-glutamyltransferase (GGT) activity was significantly increased from 80 to 120 days post-infection. Glycaemia was significantly decreased from 60 days post-infection. The average daily food intake was shown to steadily decrease until approximately 100 days. The coincidence of decreased food intake with the period of significant increase, both in AST and GLDH activities, indicated that damage caused around the time of migration of immature flukes through the liver parenchyma may be involved in appetite depression.

The effect of ethanol administration on gastric absorption in rats of two benzimidazole derivatives has been studied. The ethanol administration was carried out as both acute (5%, 10% and 15% w/v of ethanol in the perfusion solution), and chronic (15, 30 and 120 days) forms. Two benzimidazole derivatives were used: albendazole (ABZ) and mebendazole (MBZ). The administration of ethanol did not affect the kinetic mechanism of the absorption process (simple diffusion) but the absorption rate decreased in all treatments except in 5% acute ethanol, presumably due to the improved solubility of the drugs. Plasma, bile and liver levels after gastric perfusion suggest a possible interference of ethanol metabolism with drug hepatic metabolism.

1. A study was carried out to determine the kinetics of the gastric absorption of two wide spectrum benzimidazole anthelmintics, albendazole and mebendazole. 2. The method used was gastric recirculation of solutions containing the drugs in concentrations ranging from 0.5 to 100 mM. 3. The results obtained showed that absorption corresponds to first order kinetics, with diffusion constants of 0.0087 min-1 for albendazole and 0.0077 min-1 for mebendazole. 4. Blood levels of the drugs for the whole range of concentrations were always higher in the case of albendazole.

The absorptive behaviour of ofloxacin, a quinolone antibacterial agent, was studied following recirculation in small intestine of both male and female rats, at initial doses ranging from 0.125 to 5 mg mL-1. A saturable Michaelis-Menten process is suggested to explain the intestinal absorption. No significant differences were found in the absorption parameters per metabolic weight unit.

The effect of the pH of dissolutions of weakly acidic beta-lactam antibiotics on their intestinal absorption has been studied by quantification of the contribution of the ionized and un-ionized antibiotic forms to the whole absorptive process. In vivo recirculation in both sexes of adult Wistar rats was performed with buffer solutions at different pH values and samples were analyzed by high-performance liquid chromatography (HPLC).

Pyruvate kinase, activated by fructose-1,6-biphosphate from Salmonella typhimurium LT-2, has been isolated and purified to homogeneity. The enzyme, similar to that from Escherichia coli, is a tetramer with an approximate molecular weight of 240,000. The native enzyme shows optimum pH 6.8 (T = 30 degrees C). The enzymatic reaction does not require K+ ions; while Mg2+ or Mn2+ are essential for its activity. The non-activated enzyme shows sigmoid kinetics to phosphoenolpyruvate with a Hill coefficient of 2.73; the activated enzyme becomes michaelian with KSADP y KSPEP 0.25 and 0.08 mM, respectively. Both substrates excess and ATP cause enzyme inhibition. In agreement with the experimental results a steady-state random-ordered hybrid Bi-Bi mechanism with two dead-end complexes is proposed.

The mean diameter of spherical-like particles is determined by a BASIC program taking into account how the sampled diameters are distributed. In this way the numerical density of the cytoplasmic compartments is obtained. Also calculations considering Holmes' effect are provided.

A BASIC program is presented to obtain the numerical density, shape coefficient (beta) and kappa factor for the size distribution of a series of diameters measured from E.M. micrographs. Also its minimal sample size can be estimated.

Listings of BASIC and TI-59 programs are included to obtain the HPLC retention factors for beta-lactam antibiotics at given antibiotic pK's, pH, and capacity factor values, which are useful in considering the different chromatographic behaviour of antibiotics as the pH varies.

A BASIC program is presented which calculates stereological parameters from the data obtained by the analysis of cell micrographs, either by manual point-counting or semi-automatic analysis methods.

1. The effect of body weight and initial concentration on the rat small intestinal absorption of DL-8280 (ofloxacine) is studied using a recirculating perfusion technique and an improved HPLC method. 2. A prediction equation is developed under statistical and physiological considerations which correlates both factors with the intestinal absorption rate parameter Kapp.