Differential establishment and survival of Hymenolepis diminuta in syngeneic and outbred rat strains.

Experimental Hymenolepis diminuta infection was carried out in inbred strains of rats (F344/N, JAR-2, LOU/M, TM, DA and DA-bg/bg) and outbred Wistar rats. All strains became infected with this cestode, but clear strain-dependent variation in the susceptibility to H. diminuta infection was observed. Marked differences in worm persistence and worm weight were found at 6 weeks post-infection in TM and DA rats. These strains would be useful to clarify the interactions between H. diminuta and its rat host.     

Loss of Hymenolepis diminuta from the rat

One, 5, 15 and 30 worm infections of Hymenolepis diminuta were established in juvenile or adult male (Hooded Rowett or Sprague-Dawley) rats. Worm numbers and weight, and egg output were determined from day 15 to day 85 post infection. Gradual worm loss occurred only from 15 and 30 worm infections. In 5, 15 and 30 worm infections worm weight decreased from day 19 to day 50 but no weight loss occurred in single worm infections. The size range of individual worms from a multiple infection of a single rat increased markedly following infection. Adult rats showed a greater worm loss and harboured smaller worms than juvenile rats. The data will fit either a competitive or an immunological model.     

Nippostrongylus brasiliensis: physiological and metabolic responses of rats to primary infection

Primary infection of rats with Nippostrongylus brasiliensis was associated with alterations in host protein, carbohydrate and lipid metabolism. Infected rats fed ad libitum were compared with uninfected, weight matched, pair fed rats. Metabolic changes detected were related to the level of infection (larvae/g body weight) and also the time course of development of the parasite. The intestinal stage of the infection was associated with marked catabolism of skeletal muscle which did not appear to be mediated by increased secretion of corticosteroids. Plasma concentrations of protein in infected rats were altered even at the lowest dose (27 l/g), and in a biphasic manner corresponding to larval and adult stages of the parasite. Plasma globulin concentrations were increased on Day 2 after infection while from Days 5-10 after infection, plasma concentrations of both globulin and albumin were much reduced. Hypoglycemia developed on Days 8-9 after infection in rats given a dose of greater than or equal to 39 l/g. Infected rats had increased plasma concentrations of non-esterified fatty acids and in marked contrast with their pair fed partners, plasma triglyceride concentration increased dramatically with both the dose of parasites given and the duration of infection. The responses of the rat to infection with N. brasiliensis are compared with host responses to other helminths and microorganisms, and suggestions are made as to their possible functions and significance.     

Susceptibility to <Emphasis Type="Italic">Yersinia pestis</Emphasis> Experimental Infection in Wild <Emphasis Type="Italic">Rattus rattus</Emphasis>, Reservoir of Plague in Madagascar

In Madagascar, the black rat, Rattus rattus, is the main reservoir of plague (Yersinia pestis infection), a disease still responsible for hundreds of cases each year in this country. This study used experimental plague challenge to assess susceptibility in wild-caught rats to better understand how R. rattus can act as a plague reservoir. An important difference in plague resistance between rat populations from the plague focus (central highlands) and those from the plague-free zone (low altitude area) was confirmed to be a widespread phenomenon. In rats from the plague focus, we observed that sex influenced plague susceptibility, with males slightly more resistant than females. Other individual factors investigated (weight and habitat of sampling) did not affect plague resistance. When infected at high bacterial dose (more than 10⁵ bacteria injected), rats from the plague focus died mainly within 3–5 days and produced specific antibodies, whereas after low-dose infection (< 5,000 bacteria), delayed mortality was observed and surviving seronegative rats were not uncommon. These results concerning plague resistance level and the course of infection in the black rat would contribute to a better understanding of plague circulation in Madagascar.     

Effects of dietary polyamine deficiency on Trypanosoma gambiense infection in rats

Nishimura, K., Araki, N., Ohnishi, Y., and Kozaki, S. 2001. Effects of dietary polyamine deficiency on Trypanosoma gambiense infection in rats. Experimental Parasitology 97, 95-101. A diet deficient in polyamines decreases the availability of dietary polyamines. We used rats infected with the Wellcome strain of Trypanosoma gambiense to examine the effects of polyamine-deficient chow (PDC) on trypanosome proliferation and symptoms of infection. Rats fed PDC showed limited increase of trypanosome and symptoms of infection and limited loss of body weight and anemia. Survival in these rats was prolonged. Before infection, the heparinized plasma concentration of spermidine in the PDC-fed rats was lower than that in control rats fed with standard chow. After infection, the content of spermidine in red blood cells increased in the control rats, but was only slightly increased in PDC-fed rats. The content of spermidine in the trypanosomes after infection was low in the PDC-fed rats. Decreases in the polyamine content of trypanosomes limited their increase. These observations suggest that a reduction in dietary polyamines may help in the regulation of trypanosome infection.     

Hymenolepis diminuta: Worm loss and worm weight loss in long-term infections of the rat

Infections of one and two Hymenolepis diminuta established in newly weaned rats continued to grow for the duration of the experiment (238 days), whereas infections of 5 worms per rat became asymptotic around Day 55 postinfection and remained at or below this level thereafter as shown by biomass and mean weight per worm measurements. Infections of 50 worms established in newly weaned rats became asymptotic around Day 28 postinfection and thereafter worms were lost from the rats. Initially the biomass fell with the loss of worms, but by Day 56 a new lower biomass persisted for the remainder of the infection period. This level was maintained, despite diminishing numbers of worms, due to the growth of surviving individuals to a weight exceeding the original weight at maturity by a factor of more than 2. Experiments using rats that were mature at the time of infection demonstrated that the same response occurred, but approximately 3 weeks earlier.     

Parasitological and immunological aspects of Trypanosoma cruzi infection in nude rats

The role of the thymus on immunity of rats against Trypanosoma cruzi infection was investigated in vivo. The athymic (nu/nu) rats were shown to be significantly more susceptible to the acute phase of the infection than the control nu/+ rats, as measured by increased parasitemia and mortality. Specific anti-T. cruzi antibodies, complement, IgM and IgG2a serum levels were determined. The results would indicate the essential role of antibodies in immunity to acute Chagas' disease through T-dependent immune response.     

The age-related resistance of rats to Plasmodium berghei infection is associated with differential cellular and humoral immune responses

In this study, we investigated how the age of rats would affect the course of infection of and the immune response to Plasmodium berghei. Both young (4-week-old) and adult rats (8-week-old) can be infected with P. berghei ANKA strain, with significantly higher levels of infected red blood cells in young rats. While 100% of young rats succumbed to infection, adult rats were able to clear blood parasites and no mortality was observed. Analysis of cellular distribution and circulating cytokines demonstrated the persistence of CD4+/CD25+ T cells and high expression of circulating interleukin-10 (IL-10) during the progression of infection in young-susceptible rats, whereas high levels of CD8+ T cells and natural killer T cells are detected in adult-resistant rats. Analysis of antibody isotypes showed that adult rats produced significantly higher levels of interferon-gamma (IFN-gamma)-dependent IgG2c antibodies than young rats during infection. Further evaluation of the role of IL-10, IFN-gamma and of immune cells showed that only the adoptive transfer of spleen cells from adult-resistant rats was able to convert susceptibility of young-susceptible rats to a resistant phenotype. These observations suggest that cell-mediated mechanisms are crucial for the control of a primary infection with P. berghei in young rats.     

Morphine reduces pulmonary inflammation in response to influenza infection.

The present study shows that morphine reduces the pulmonary inflammatory response to intranasal influenza virus infection in rats. Rats were infected with rat-adapted influenza virus (RAIV), which is a unique infectious agent because normal rats develop an acute pulmonary inflammatory response to RAIV and rapidly clear the virus within a few days with no mortality. Male Lewis rats were implanted with 75 mg morphine pellets or placebo pellets 72 hours prior to intranasal RAIV infection. Rats were euthanized at 2, 24, 48, 72, and 96 hours after infection. Assessment of inflammation included accumulation of inflammatory cells in the lungs, lung weight, and protein and LDH content of bronchial alveolar lavage fluid (BALF). Placebo-treated rats showed a marked inflammatory response to RAIV infection, and morphine-treated rats mounted less vigorous inflammatory responses to the infection. Taken together, these data suggest that morphine treatment impairs the inflammatory response to RAIV infection in the lungs, which is consistent with prior work demonstrating that morphine is a potent anti-inflammatory agent in other areas of the body.     

Studies on the chemoprophylaxis of subperiodic Brugia malayi infection in the leaf monkey (Presbytis melalophos) with diethylcarbamazine citrate

The chemoprophylactic use of diethylcarbamazine citrate at total oral doses of 15--180 mg/kg body weight was tested against subperiodic Brugia malayi infection in the leaf monkey (Presbytis melalophos). A total dose of 45 mg/kg body weight given over 9 days killed all developing infective larvae. Similarly, a total dose of 35 mg/kg body weight given over 7 days killed all fourth stage larvae. The minimum effective dose that prevents infection would be 5 mg/kg body weight daily for 7 days every month.     

Serum leptin, lipids, free fatty acids, and fat pads in long-term dehydroepiandrosterone-treated Zucker rats

The obese Zucker rat has a genetically flawed leptin system and is a model of hyperphagia, obesity, hyperlipidemia, and markedly elevated leptin levels. Dehydroepiandrosterone (DHEA) administration reduces hyperphagia, hyperlipidemia, and obesity in Zucker rats. Since serum leptin levels are associated with body fat, we wondered what the effects of fat pad weight reduction from DHEA administration would have on leptin levels. This experiment investigated the effects of DHEA on intra-abdominal fat pads, serum lipids, and peripheral leptin in male lean and obese Zucker rats that were administered DHEA in their food from 4 weeks of age to 20 weeks. Lean and obese rats received plain chow or chow containing DHEA. Additional chow-fed groups of lean and obese weight-matched controls and obese pair-fed rats helped to control for the reduced body weight, food intake, and fat pad weights seen with DHEA administration. DHEA administration to lean Zucker rats reduced body weight and fat pad weights, but leptin levels showed a lower trend. Among obese rats, both DHEA treatment and pair-feeding reduced body weight and fat pad weights, but only DHEA lowered leptin levels. The weight-matched controls had reductions in fat pad weights similar to the DHEA-treated group, but with increased leptin levels. Thus, DHEA may exert a small, independent effect on leptin levels in this animal model, but the reduction is less than what would be expected.     

Host age and the growth and fecundity of Hymenolepis diminuta in the rat

Five, 20, and 80 cysticercoid infections of Hymenolepis diminuta were established in 1-, 2- and 5-month-old male Wistar rats. Worm numbers, dry weights and egg outputs were determined on day 28 post infection. Worm recovery was found to be independent of cysticercoid dose in 1-month-old rats, but density-dependent in older rats. Density dependence affected both worm dry weight and egg production in all 3 age classes of host studied. However, at the highest dose both dry weight and egg production were significantly decreased in 2- and 5-month-old rats compared with 1-month-old rats. The results cannot be explained solely in terms of competition for a resource, and suggest that immunological mechanisms may have an important role in the "crowding effect".     

Trichinella spiralis in an agricultural ecosystem: transmission in the rat population

Four hundred forty-three Norway rats (Rattus norvegicus) were examined to determine their role in the transmission and maintenance of Trichinella spiralis on a pig farm. Rats, classified by sex and weight, were examined for trichinellosis by peptic digestion of muscle samples. Over a 25-mo period, 188 (42.4%) rats were found to be infected with T. spiralis. The mean intensity of infection was 293.2 larvae per gram (LPG) of muscle; 65 (34.6%) infected rats had intensities of infection greater than 100 LPG. Even in the absence of a known source of infected meat (garbage containing meat scraps or dead animals), the rat population maintained the infection, probably through cannibalism. Population reduction was an effective method for reducing the prevalence of infection within the rat population. Therefore, to reduce the likelihood of transmission of T. spiralis between rats and swine, it is essential that rat populations in a farmyard environment be controlled.     

A decrease in thymus-mediated immune responses as a result of treatment of neonatal rats with glutamate

We investigated whether administration of monosodium l-glutamate (MSG) to neonatal rats would disrupt immune responses in intact and orchidectomized adult male rats. Neonatal male rats were treated with saline or MSG which causes severe endocrine abnormalities. Half of each group of animals were orchidectomized as adults and killed one week later along with intact rats. MSG treatment resulted in suppressed serum LH levels in intact rats. Thymus weight and spleen cellularity in intact animals were not affected by MSG treatment, but thymus weight increased within one week after orchidectomy in both saline- and MSG-treated groups. In intact rats, lymphocyte stimulation by the T cell specific mitogens (concanavalin A or phytohemagglutinin) or the B cell specific mitogen (lipopolysaccharide) was unaffected by prior treatment with MSG. However, MSG treatment blocked the decrease attributable to orchidectomy in concanavalin A and phytohemagglutinin stimulation of lymphocyte blastogenesis. The results suggest that administration of MSG to neonatal male rats can alter some immune responses in the adult animal.     

Protection against the diabetogenic effect of feeding tert-butylhydroquinone to rats prior to the administration of streptozotocin

We determined whether an oral administration of the synthetic antioxidant, tert-butylhydroquinone (TBHQ), or the naturally occurring lipoxygenase inhibitor, curcumin, to rats would provide protection against the diabetogenic effect of streptozotocin (STZ). Male Sprague-Dawley rats were fed on an AIN-76-based purified diet containing 0.0028% TBHQ or on the purified diet with a daily intragastric administration of curcumin (200 mg/kg of body weight) for one week while receiving intravenously administered STZ. The rats fed on the TBHQ-containing diet were resistant to diabetes development when compared with the rats fed on the TBHQ-free diet and had a higher body weight gain and lower serum glucose concentration. Glucose-stimulated insulin secretion from the pancreatic islet in the rats that had received TBHQ was higher than that in the control rats. The rats receiving curcumin showed no beneficial effect on these diabetic symptoms. These findings provide direct evidence for the suggestion that dietary supplementation of an antioxidant may exert a preventive effect on the diabetogenic action of free-radical producers.     

A physiological level of clenbuterol does not prevent atrophy or loss of force in skeletal muscle of old rats.

Supraphysiological levels of clenbuterol (CL) reduce muscle degradation in both young and old animals; however, these pharmacological levels induce side effects that are unacceptable in the elderly. In this study, we tested the hypothesis that a "physiological" dose of CL (10 microg. kg(-1). day(-1)) would attenuate the loss of in situ isometric force and mass in muscles of senescent rats during hindlimb suspension (HS). Adult (3 mo) and senescent (38 mo) Fischer 344 x Brown Norway rats received CL or a placebo during 21 days of normal-weight-bearing or HS conditions (8 rats/age group). HS reduced soleus muscle weight-to-body weight ratio by 31%, muscle cross-sectional area by 37%, and maximal isometric tetanic force (P(o)) by 76% in senescent rats. CL attenuated the loss of P(o) and muscle weight by 17 and 8%, respectively, in the soleus of senescent rats relative to HS+placebo conditions, but it did not improve muscle weight normalized for body weight. CL did not reduce the decrease in soleus P(o) or mass after HS in adult rats. CL failed to reduce the loss of plantaris weight (-20%) and P(o) (-46%) in senescent rats after HS. Our data support the conclusion that physiological levels of CL do not improve fast muscle atrophy and only modestly reduce slow muscle atrophy, and, therefore, it is largely an ineffective countermeasure for preventing muscle wasting from HS in senescent rats.     

Effects of Weight Cycling Induced by Diet Cycling in Rats Differing in Susceptibility to Dietary Obesity

LAUER, JOAN B., GEORGE W. REED, AND JAMES O. HILL. Effects of weight cycling induced by diet cycling in rats differing in susceptibility to dietary obesity. Obes Res. Objective Although the majority of evidence in rodents does not support the view that weight cycling (consisting of bouts of food restriction and refeeding) promotes obesity, the effects of weight cycling on body weight regulation remain controversial. We have previously demonstrated that some rats within a strain are more susceptible to develop obesity than others when given free access to a high-fat diet. In this study, we tested the hypothesis that rats most susceptible to weight gain on a high-fat diet would also be most susceptible to weight gain as a consequence of weight cycling. Research Methods and Procedures Rats were provided a low-fat diet (12% corn oil) for 2 weeks, then given a high-fat diet (45% corn oil) for 2 weeks to identify those most (obesity prone) and least (obesity resistant) susceptible to weight gain. Half of each group was then subjected to three 30-day cycles of food restriction (10 days) and refeeding (20 days) [weight cycler (WC) rats]. The other half were allowed free access to the high-fat diet [control (CO) rats]. All rats were then followed for an additional 10 weeks, with free access to the high-fat diet. Results When considering the entire 160 days of the study, we found no evidence that WC rats relative to CO rats had increased body weight, increased body fat content, or elevated energy efficiency. We found no evidence that rats most prone to dietary obesity were also prone to weight gain after weight cycling. During the weight cycling phase (days 1 to 90), weight cycled groups consumed less energy and gained less weight than controls. During the follow-up phase, WC and CO rats did not differ significantly in weight gain or energy intake. Discussion In this study, weight cycling did not exacerbate the obesity produced by high-fat diet feeding.     

Effect of epinephrine on the oxidative desaturation of fatty acids in the rat.

The effect of epinephrine on the oxidative desaturation of fatty acids by liver microsomal preparations of rats has been studied. Administration of epinephrine (1 mg/kg body weight) produced a significant decrease in desaturation of [l-14C]=linoleic acid to gamma-linolenic acid and of [L-14C]alpha-linolenic acid to actadeca-6,9,12,15-tetraenoic acid 12 hr after the infection. Lower doses produced a lesser effect on the delta6-desaturation activity. Epinephrine administration modified the V max of linoleic acid desaturation but not the K m. There was also a slight increase in palmityl desaturation activity. The effect of epinephrine on delta6-desaturation activity was postulated to be mediated through an enhancement of the intracellular cyclic AMP levels that lead to an increase of a glucose metabolite. This metabolite would inhibit delta6-desaturation activity.     

Nippostrongylus brasiliensis: changes in plasma levels of gastrointestinal hormones in the infected rat

Plasma concentrations of gastrointestinal hormones were measured by radioimmunoassay in fasted rats 9 days after infection with a range of doses of Nippostrongylus brasiliensis. Values for infected rats fed ad libitum were compared with those of weight matched, pair fed, uninfected rats to control for the possible effects of dose-dependent reductions in food intake associated with infection. The plasma concentrations of some of the gastrointestinal hormones in infected rats were very different from those of their pair fed partners. The magnitude and direction of the changes varied according to the hormone being examined. Plasma concentrations of gastrin and pancreatic polypeptide were similar in pair fed and infected rats at all doses used. For the other hormones assayed, infection was associated with dose-related changes. The plasma concentrations of cholecystokinin and insulin were slightly but significantly reduced in infected rats. In contrast, secretin, enteroglucagon, and pancreatic glucagon concentrations were markedly increased. At the highest dose given (52 larvae/g body wt), the plasma levels of secretin and enteroglucagon in infected rats were elevated 9 X and 15 X, respectively. A comparison of the changes seen in N. brasiliensis-infected rats with those reported for other helminth infections revealed striking differences. The possible etiology of alterations in plasma gastrointestinal hormone concentrations and their contribution to the pathological changes seen in animals infected with helminths are discussed.     

Effect of surgical alteration of the rat gastrointestinal tract on the growth and development of Hymenolepis diminuta

Eight groups of rats were used to study the involvement of the enteric (ENS) and central (CNS) nervous systems in the development of Hymenolepis diminuta using surgical intestinal transection, or CNS denervation, or both procedures. The transection procedure was used to isolate the ENS of the small intestine from either orad and/or caudal portions of the alimentary system, while the CNS denervation was used to eliminate direct visceral efferent inputs from the CNS. Nine days after the surgical procedures, all rats were infected with 35 cysticercoids of H. diminuta. On 20 days postinfection, the infection intensity, tapeworm dry weight, tapeworm morphology, intestine length, and intestinal wet weight were recorded. Only the combination of the duodenal and ileal transections with a CNS denervation reduced infection intensity and prevented the increased intestinal length normally observed in infected rats. In contrast, none of the various intestinal transection procedures alone or CNS denervation alone had any effect on the survival, ability to produce oncospheres or morphology of the tapeworms. In conclusion, tapeworm survival is decreased when both CNS and ENS inputs into the small intestine are altered or absent.