Vaccination with protein-conjugated and native type 3 capsular polysaccharide in an ethanol-fed rat model of pneumococcal pneumonia

A chronic ethanol-fed rat model was used to determine the effect of alcohol ingestion on production of antibody to type 3 pneumococcal capsular polysaccharide. Sprague-Dawley rats were fed a liquid diet containing 36% of calories as ethanol (ethanol-fed), an isocaloric diet containing dextrin-maltose (pair-fed) or standard rat chow (chow-fed). After 7 days of feeding, the rats were vaccinated subcutaneously with placebo or with either 25 microg of type 3 pneumococcal capsular polysaccharide (SpnCP) or 5 microg of SpnCP linked to the protein carrier CRM197 (SpnCP/CRM197). Rats given the conjugated vaccine received a booster injection 14 days later. Maximum antibody titers were observed six days postvaccination for rats given SpnCP alone and 21 days postvaccination for rats given SpnCP/CRM197. All rats were infected transtracheally with 2-3 times the expected lethal dose50 for each feeding group of type 3 Streptococcus pneumoniae on the day of peak antibody titers. Mortality was recorded for a 10-day period. Vaccination with SpnCP increased survival of ethanol- and chow-fed, but not pair-fed rats. This protection was only statistically significant in the chow-fed group (p < 0.01). Vaccination with SpnCP/CRM197 moderately increased survival of rats in all three feeding groups, but this was not statistically significant in any of them.     

Behavior and drug measurements in Long-Evans and Sprague-Dawley rats after ethanol-cocaine exposure

Long-Evans and Sprague-Dawley rats show differential behavioral responses to cocaethylene, a metabolite derived from the simultaneous ingestion of ethanol and cocaine. Such differences may also be manifested when these outbred strains are exposed to ethanol and cocaine. To test this hypothesis, both strains were fed an ethanol-diet (8.7% v/v) in conjunction with cocaine (15 mg/kg) injections for 15 days. The following parameters were evaluated: (a) ethanol consumption, (b) cocaine-induced behavioral activity, (c) blood ethanol levels, (d) blood, liver, or brain cocaine and cocaethylene levels, and (e) liver catalase and esterase activity. We found that Long-Evans rats drank significantly more of the ethanol diet relative to the Sprague-Dawley line during the first few days of the test session. This rat phenotype also differed significantly from the Sprague-Dawley line in terms of behavioral activity after cocaine administration. Blood ethanol levels did not differ between strains. Similarly, we failed to detect strain-dependent differences in blood, liver, or brain cocaine levels as measured by gas chromatography/mass spectrometry. Cocaethylene levels, however, were higher in blood and brain of Long-Evans relative to Sprague-Dawley cohorts. Although the ethanol-cocaine regimen produced a marked suppression of catalase and esterase activity compared with control-fed rats, this suppression was roughly equivalent in both rat phenotypes. These data are discussed in the context of genotypic background and vulnerability to polysubstance abuse.     

The Montignac method: scientific foundation debatable

Obesity is a major health issue in Western society. In the Netherlands every fifth person suffers from obesity and every third person is on a weight-reducing diet. The Montignac method is a very popular diet. The diet is claimed to be a nutritional science. The method is based on several hypotheses about the metabolism of carbohydrates and fatty acids: carbohydrates with a low glycaemic index are preferred, carbohydrates are not to be eaten in combination with fatty acids, fruit is propagated but must not be combined with other components. The scientific literature refutes the hypotheses of Montignac regarding the metabolic effects of carbohydrates and fatty acids. As a method to lose weight, the conventional recommendations of caloric restriction, less intake of saturated fatty acids and more physical activity should be preferred to the Montignac diet.     

Four-week ethanol intake decreases food intake and body weight but does not affect plasma leptin, corticosterone, and insulin levels in pubertal rats

Long-term intake of ethanol decreases food intake and inhibits growth in experimental rats. The aim of this study was to determine the effect of 4-week oral ethanol ingestion on plasma leptin and adrenal function. Male 45-day-old Wistar rats were divided into three groups: absolute control (AC), ethanol (E) administered 10% (wt/vol) ethanol instead of tap water, and pair-fed (PF) given an amount of food corresponding to the food intake of E animals. E rats consumed less pelleted diet (74% cumulative total intake); however, this caloric deficit was compensated by ethanol ingestion. Net water intake in E animals was 76% of that in the control groups. The body growth of both E and PF rats was stunted compared with AC animals, but E rats were heavier than PF rats. The plasma leptin level was similar in E and AC and decreased in PF animals. There were no differences in plasma osmolality or glycemia among the three groups. Plasma insulin was decreased in PF compared with both AC and E rats. Plasma corticosterone was not affected by ethanol, but was increased in the food-restricted (PF) group. Although there were no differences in basal adrenal corticosterone production in vitro, there was a slightly higher response to corticotropin (ACTH) in E rats. We conclude that drinking 10% ethanol decreased the dietary intake and body growth. These changes were not mediated by plasma leptin changes. Although alcohol ingestion and its energy content theoretically normalized the total energy intake and prevented the decrease of plasma leptin, the growth of young rats was inhibited. Drinking 10% ethanol instead of tap water for 4 weeks did not stimulate basal adrenal activity.     

Effect of glycerol on lipogenic enzyme activities and on fatty acid synthesis in the rat and chicken

The influence of glycerol on the rates of fatty acid snythesis in liver slices from rats and chickens in pieces of adipose tissue from rats was first studied. Then the effect of dietary glycerol on lipid metabolism in rats and cheickens was examined. Media containing 3 or 10 mM glycerol depressed the rate of glucose conversion to fatty acids in rat liver slices. However, media containing up to 25 mM glycerol did not influence the rate of fatty acid synthesis in chick liver slices. The inhibitory action of glycerol in rat liver slices might occur at the level of glucose (or glycogen) conversion to pyruvate because glycerol did not inhibit pyruvate or acetate conversion to fatty acids. Rats and chickens were fed glycerol containing diets for either 3 days or 3 weeks. Feeding diets containing 20.5 parts glycerol (22% of dietary energy) to rats or chickens did not influence the growth rate of the animals. However, substitution of 42.2 parts glycerol (43% of dietary energy) for glucose in the diet significantly depressed food intake and growth rate in both rats and chickens. The activities of citrate cleavage enzyme, fatty acid synthetase and malic enzyme in livers of rats fed the glycerol-containing diets were dramatically increased. However, this stimulation of enzyme activity occurred without a concomitant increase in the in vivo rate of fatty acid synthesis in the rat liver. In the chicken, unlike the rat, dietary glycerol did not stimulate but instead decreased hepatic malic enzyme and fatty acid synthetase activities. No significant differences in adipose tissue lipogenic enzyme activities or in the rates of fatty acid synthesis were observed in rats fed glycerol-containing diets. The lipogenic response to glycerol feeding depends on the species as well as the organ.     

Quinolone antibiotics in therapy of experimental pneumococcal meningitis in rabbits

Using a rabbit model of pneumococcal meningitis, we compared the pharmacokinetics and bactericidal activities in cerebrospinal fluid (CSF) of older (ciprofloxacin, ofloxacin) and newer (levofloxacin, temafloxacin, CP-116,517, and Win 57273) quinolones with those of the beta-lactam ceftriaxone. All quinolones penetrated into the inflamed CSF better than ceftriaxone, and the speed of entry into CSF was closely related to their degrees of lipophilicity. At a dose of 10 mg/kg.h, which in the case of the quinolones already in use in clinical practice produced concentrations attainable in the sera and CSF of humans, ciprofloxacin had no antipneumococcal activity (delta log10 CFU/ml.h, +0.20 +/- 0.14). Ofloxacin (delta log10 CFU/ml.h, -0.13 +/- 0.12), temafloxacin (delta log10 CFU/ml.h, -0.19 +/- 0.18), and levofloxacin (delta log10 CFU/ml.h, -0.24 +/- 0.16) showed slow bactericidal activity (not significantly different from each other), while CP-116,517 (delta log10 CFU/ml.h, -0.59 +/- 0.21) and Win 57273 (delta log10 CFU/ml.h, -0.72 +/- 0.20) showed increased bactericidal activities in CSF that was comparable to that of ceftriaxone at 10 mg/kg.h (delta log10 CFU/ml.h, -0.80 +/- 0.17). These improved in vivo activities of the newer quinolones reflected their increased in vitro activities. All quinolones and ceftriaxone showed positive correlations between bactericidal rates in CSF and concentrations in CSF relative to their MBCs. Only when this ratio exceeded 10 did the antibiotics exhibit rapid bactericidal activities in CSF. In conclusion, in experimental pneumococcal meningitis the activities of new quinolones with improved antipneumococcal activities were comparable to that of ceftriaxone.     

The effects of patterned calorie-restricted diets on mammary tumor incidence and plasma endothelin levels in DMBA-treated rats

Chronic caloric restriction has been shown to inhibit mammary tumor promotion in the 7,12-dimethyl-benz[a]anthracene (DMBA) rat mammary tumor model. The objectives of this study were to determine (i) the effects of chronic caloric cycling (yo-yo dieting) on mammary tumor promotion by high fat diets and (ii) the effect of three dietary regimens +/- superimposed mammary tumor burden on plasma endothelin-1,2 (ET) levels. Female Sprague-Dawley rats were treated with DMBA (5 mg/rat) and divided into three dietary groups: ad libitum (AL) (containing 15% corn oil); 40% calorie restricted (CR) (containing 20% corn oil so consumption of fat was equivalent between AL and CR); a calorie cycled (CC) group fed alternatively AL and CR diets each 48 h period. After 10 weeks, tumor incidences were: AL, 63%; CR, 27%; CC, 57% (AL versus CR, P < 0.05; CC versus CR, P < 0.05; AL versus CC, NSD). ET levels (pg/ml plasma) were: AL, 16.0 +/- 6.54; CR, 32.31 +/- 0.34; CC, 23.44 +/- 5.04 (AL versus CR, P < 0.01; CC versus CR, P < 0.01; AL versus CC, P < 0.05). Plasma ET levels were independent of tumor incidence and tumor burden, but plasma ET levels were significantly increased in rats with a prior history of calorie restriction. As expected, maintained caloric restriction reduced mammary tumor incidence but intermittent caloric restriction (caloric cycling or yo-yo dieting) was without similar benefit.     

Timing of onset of contraceptive effectiveness in Depo-Provera users. II. Effects on ovarian function

1. Microsomal P450 and peroxisomal fatty acid oxidation activities were studied in liver of rats after long-term ethanol consumption. 2. Ethanol increased the microsomal lauric acid omega-hydroxylation and the aminopyrine N-demethylation catalyzed by cytochrome P450. 3. Ethanol increased peroxisomal beta-oxidation of palmitoyl CoA and catalase activity in liver. 4. Both microsomal and peroxisomal activities behaved in a coordinate way in the liver of rats with long-term ethanol consumption. 5. These results would support a role of microsomal omega-hydroxylation and peroxisomal beta-oxidation of fatty acids in an extramitochondrial pathway of lipid oxidation in the liver.     

Carnitine supplementation accelerates normalization of food intake depressed during TPN

When total parenteral nutrition (TPN; containing glucose, fat, and amino acids; caloric ratio 50:30:20) providing 100% of the rat's daily caloric intake is given for 3-4 days, food intake rapidly decreases by approximately 85%. After stopping TPN, there is a lag period of 3-4 days before food intake returns to previous level, which appears to be related to fatty acid oxidation and fat deposition. Carnitine plays a key role in the oxidation of fatty acids, and was demonstrated to reduce fat deposition in rats receiving TPN, by increasing beta oxidation. We therefore investigated whether rats receiving TPN supplemented with carnitine may prevent either the decrease or speed up the resumption or normalization of food intake, after TPN is stopped. Fourteen adult Fischer-344 rats had a central venous catheter inserted. After 10 recovery days, controls (n = 7) were infused with TPN providing 100% of rat's daily caloric intake for 3 consecutive days, followed by 4 more days of normal saline. The carnitine group (n = 7) received the same solution, but which provided 100 mg/kg/day carnitine. Daily food intake was measured and data were analyzed using ANOVA and Student's t-test. Both parenteral solutions depressed food intake maximally by almost 90% by day 3. Carnitine accelerated the normalization of food intake by decreasing the lag period by 1 day. We conclude that the addition of carnitine enhanced the normalization of post-TPN food intake and argue that this may be on the basis of enhanced fatty acid oxidation, a substrate known to play a significant role in the anorexia induced by TPN.     

A model of the cerebellum in adaptive control of saccadic gain. I. The model and its biological substrate

Muscle tissue (1.1 +/- 0.1 grams) was obtained from seven healthy individuals (3 males, 4 females) using an open incision approach before and after ingestion of either 75 grams of dextrose (N=5) or water (N=2). Purified sarcolemmal membranes from the muscle were prepared using a sucrose step gradient. A polyclonal antibody raised against the purified (99%) rat hepatocyte 40 KD membrane fatty acid binding protein (mFABP-L) was used to probe for this putative transporter in the muscle membranes using Western blot. A single band at the 40 KD MW band was identified which reacted antigenically with the protein purified from rat livers. These response of Berk's protein 60-75 minutes after dextrose ingestion (or water) was erratic and no specific trend could be identified. Our data demonstrate that the 40 KD mFABP-L originally isolated from rat liver is also present in human skeletal muscle membrane. This protein may be involved in transport of fatty acids across the membrane of skeletal muscle, however its physiological role in human fatty acid metabolism remains to be established.     

Effects of chronic ethanol consumption on extramitochondrial fatty acid oxidation and ethanol metabolism by rat kidney

1. We evaluated the effects of chronic ethanol consumption on microsomal and peroxisomal fatty acid oxidation and on ethanol oxidation by the kidney. 2. When mature rats were fed 20% ethanol for 10 weeks, an increase in alcohol dehydrogenase and catalase activities were observed in the kidney. 3. Renal microsomal and peroxisomal oxidation of fatty acids also increased by the treatment, but total cytochrome P450 content did not. 4. We concluded that chronic ethanol consumption results in an increased extramitochondrial disposition of fatty acids and ethanol oxidation by the kidney.     

Short-term ozone exposure affects the surface activity of pulmonary surfactant

The effects of short-term ozone exposure on the lung function and surface activity of surfactant subtypes isolated from rat lung lavage were studied. Rats were exposed to 0.8 ppm ozone for 2 or 12 hr. The surface activity of surfactant was affected by ozone exposure, whereas distinct morphological changes in bronchoalveolar lavage or in the surfactant subtypes were not observed. Adsorption experiments indicated that bronchoalveolar lavage from rats exposed for 12 hr to ozone remained at lower equilibrium surface pressures than lavage from control rats. These observations suggest interference of inflammatory proteins with the surface film. Extracted surfactant, containing only lipids and surfactant proteins B and C, had a decreased adsorption rate after ozone exposure. These results suggest that the activity of one or both of the hydrophobic surfactant proteins (SP-B and SP-C) was affected by ozone.     

DNA sequence recognition by bis-linked netropsin and distamycin derivatives

The dihydropyridine receptor (DHPR), a voltage-gated L-type Ca2+ channel, and the Ca2+ release channel/ryanodine receptor isoform-1 (RyR1) are key molecules involved in skeletal muscle excitation-contraction coupling. We have reported age-related decreases in the level of DHPR expression in fast- and slow-twitch muscles from Fisher 344 cross Brown Norway (F344BNX) rats (Renganathan, Messi and Delbono, J. Membr. Biol. 157 (1997) 247-253). Based on these studies we postulate that excitation-contraction uncoupling is a basic mechanism for the decline in muscle force with aging (Delbono, Renganathan and Messi, Muscle Nerve Suppl. 5 (1997) S88-92). In the present study, we extended our studies to older ages and we intended to prevent or retard excitation-contraction uncoupling by restricting the caloric intake of the F344BNX rats from 16 weeks of age. Three age groups, 8-, 18-, and 33-month old caloric restricted rats, were compared with ad libitum fed animals. The number of DHPR and RyR1 and DHPR/RyR1 ratio (an index of the level of receptors uncoupling) in skeletal muscles of 8-month and 18-month rats was not significantly different in either ad libitum fed or caloric restricted rats. However, the age-related decrease in the number of DHPR, RyR1 and DHPR/RyR1 ratio observed in 33-month old ad libitum fed rats was absent in 33-month old caloric restricted rats. These results suggest that caloric restriction prevents age-related decreases in the number of DHPR, RyR1 and DHPR/RyR1 ratio observed in fast- and slow-twitch rat skeletal muscles.     

Changes in fatty acid composition in rat adipose tissue induced by dietary obesity

The aim of the study was to evaluate the effects of cafeteria feeding on the composition of fatty acids in retroperitoneal fat pad and also to determine what happens to fatty acids when rats previously fed the cafeteria diet are returned to regular rat chow. The study of the post-cafeteria rats enabled us to determine the effects of dietary induced excess weight in the absence of artefactual interferences from the diet because these rats, unlike the cafeteria obese rats, ate the same diet as controls. In response to cafeteria feeding there were increases in the majority of adipose tissue fatty acids. However, significant decreases were observed in the relative proportions of 18:2n-6 and in two related n-6 polyunsaturated fatty acids (18:3n-6 and 20:3n-6), as well as in 16:1. In the post-cafeteria obesity model the previous dietary influence on fatty acid composition was still evident. The maintenance of both the high levels and proportions of 18:1 and the decrease of 16:1 percentage in the post-cafeteria rats argues in favour of an alteration in the activity of the elongation metabolic pathway. Certain changes affecting polyunsaturated fatty acid adipose depot composition of obese rats, mainly the decreased levels of 18:2n-6, are long lasting and could be related to the maintenance of the obese status. On the whole, although the fatty acid composition of adipose tissue is influenced by the composition of the diet, there are some differences in both the maintenance of the effects and also in the selectivity of adipose tissue for the different fatty acids of obese and lean rats.     

Free fatty acid fractions from some vegetable oils exhibit reduced survival time-shortening activity in stroke-prone spontaneously hypertensive rats

Previously, we demonstrated that several vegetable oils that included low-erucic rapeseed oil markedly shortened the survival time (by approximately 40%) of stroke-prone spontaneously hypertensive (SHRSP) rats as compared with perilla oil, soybean oil, and fish oil. We considered that a factor other than fatty acids is toxic to SHRSP rats, because the survival time-shortening activity could not be accounted for by the fatty acid compositions of these oils. In fact, a free fatty acid (FFA) fraction derived from lipase-treated rapeseed oil was found to be essentially devoid of such activity. A high-oleate safflower oil/safflower oil/perilla oil mixture exhibited a survival time-shortening activity comparable to that of rapeseed oil, but the activity of this mixed oil was also reduced by lipase treatment. A partially hydrogenated soybean oil shortened the survival time by approximately 40%, but a FFA fraction derived from lipase-treated partially hydrogenated soybean oil shortened it by 13% compared with soybean oil. Fatty acid compositions of the rapeseed oil and a FFA fraction derived from lipase-treated rapeseed oil were similar, but those of hepatic phospholipids of rats fed the oil and FFA were slightly but significantly different. These results support the interpretation that the survival time-shortening activity exhibited by some vegetable oils is due to minor components other than fatty acids, and that an active component(s) were produced in or contaminated soybean oil during the partial hydrogenation processes.     

Dietary self-selection of golden hamsters in response to acute food deprivation and chronic food restriction.

Adult male golden hamsters were maintained on either Purina Rat Chow (Chow diet) or a self-selection diet consisting of high-protein chow, pure fat, and pure carbohydrate (Choice diet). In Experiment 1, animals were deprived of food for single periods of up to 48 hr. Animals on the Chow diet did not increase intake at any time after deprivation; animals on the Choice diet selectively increased their consumption of fat-derived calories and increased their total caloric intake during the first 6 hr of refeeding, but not thereafter. The nature of the diet did not influence the rate at which animals regained weight following deprivation. In Experiment 2, hamsters were placed on food-restriction schedules (access to food either for 1 hr/day only or on alternate days only) until they lost 20% of starting body weight. Chow-fed animals demonstrated little or no change in food intake either during or after food restriction. Hamsters on the Choice diet consumed more calories and lost weight more slowly than did chow-fed animals during 1-hr/day feeding; intake of fat-derived calories was elevated during restriction. Choice hamsters increased total caloric intake only towards the end of the alternate-days restriction schedule. Choice hamsters were hyperphagic following both types of food-restriction schedules, but no increased preference for fat-derived calories was observed. Factors influencing food consumption of hamsters in response to deprivation and restriction are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Peroxisomes are involved in the swift increase in alcohol metabolism

The purpose of this study was to determine whether catalase-dependent alcohol metabolism is activated by alcohol (i.e., swift increase in alcohol metabolism). When ethanol or the selective substrate for catalase, methanol, was given (5.0 g/kg) in vivo 2 to 3 h before liver perfusion, methanol and oxygen metabolism were increased significantly. This increase was blocked when the specific Kupffer cell toxicant GdCl3 was administered 24 h before perfusion. These data support the hypothesis that catalase-dependent alcohol metabolism is activated by acute alcohol and that Kupffer cells are involved. Ethanol treatment in vivo increased ketogenesis from endogenous fatty acids nearly 3-fold and increased plasma triglycerides and hepatic acyl CoA synthetase activity; all increases were blocked by GdCl3. These findings support the hypothesis that ethanol increases H2O2 supply for catalase-dependent alcohol metabolism by increasing fatty acid supply. Infusion of oleate stimulated oxygen uptake 1.5-fold and methanol metabolism 4-fold, but these parameters were not altered by GdCl3. Moreover, the effects of ethanol treatment were blocked by the cyclooxygenase inhibitor indomethacin, and prostaglandin E2 (PGE2) was increased more than 200% in media from cultured Kupffer cells from rats treated with ethanol in vivo. Furthermore, lipoprotein lipase activity in retroperitoneal fat pads, which is known to be inhibited by PGE2, was reduced 70% by ethanol. These data are consistent with the hypothesis that Kupffer cells play a key role in activation of catalase-dependent alcohol metabolism, most likely by producing mediators (e.g., PGE2) that inhibit lipoprotein lipase, increase the supply of fatty acids to the liver, and increase generation of H2O2 via peroxisomal beta-oxidation.     

The effect of over- and undernutrition on cancer

Overnutrition, as a factor in carcinogenesis, has been a matter of concern for over 80 years. Overnutrition relates to excess intake of calories, and fat is the major contributor to caloric burden. Thus, fat has been the focus of many epidemiological studies, but as long ago as 1975 some investigators were suggesting that excess energy intake might be the major factor relating to cancer incidence. Ecological studies support the idea that a high fat (high energy?) diet may represent a risk for cancer but case-control or follow-up studies generally do not. The effects of undernutrition have been studied experimentally. Mostly conducted in rats or mice, they show virtually uniformly that caloric (energy) restriction inhibits the growth of spontaneous, transplanted or induced tumours. The effect is observed even when the calorie-restricted animals ingest more fat than do the controls. Energy utilization via exercise reduces tumour growth in rats and a life history of physical labour reduces risk in man. The mechanism(s) by which caloric restriction exerts its effects are moot, but it has been shown to reduce insulin levels and to reduce oncogene expression. Energy restriction also increases activity of antioxidant enzymes and leads to enhanced DNA repair. Increased energy flux (by means of decreased intake or increased output) may provide a simple and inexpensive approach to reducing the risk of cancer in man.     

Schooling, employment, and idleness in young adults with serious physical health conditions: effects of age, disability status, and parental education

Aging is associated with significant structural and functional changes in the gastrointestinal tract. Gastrin, a hormone produced by G cells in the antrum of the stomach, stimulates proliferation of gastric mucosa; its synthesis appears to decrease with age. Life-long restriction of caloric intake is the only experimental manipulation that has been shown to retard aging processes in rats. The purpose of this study was to examine the effect of short-term caloric restriction (CR) on the production and release of the hormone gastrin with aging. Aging causes a fall in both fasting plasma levels of gastrin and antral content of gastrin in Fischer 344 rats; short-term CR appears to augment this age-related decrease. Steady state levels of antral gastrin mRNA were decreased with aging, and short-term CR resulted in an augmented decrease in aged, but not in young rats. Our findings indicate that gastrin release, synthesis and gene expression decrease with age. Restriction of the caloric intake for a short period (i.e. 8 weeks) augments this age-related decrease in antral gastrin and fasting plasma levels. Short-term CR appears to decrease the production of gastrin at the level of gene expression.