Effect of Fidarestat and α-Lipoic Acid on Diabetes-Induced Epineurial Arteriole Vascular Dysfunction

In the present study, the authors examined whether treating streptozotocin-induced diabetic rats with the combination of α-lipoic acid and fidarestat, an aldose reductase inhibitor, can promote the formation of dihydrolipoic acid in diabetic animals and thereby enhance the efficacy of α-lipoic acid as monotherapy toward preventing diabetic vascular and neural dysfunction.Treating diabetic rats with the combination of 0.25% α-lipoic acid (in the diet) and fidarestat (3 mg/kg body weight) prevented the diabetesinduced slowing of motor nerve conduction velocity and endoneurial blood flow. This therapy also significantly improved acetylcholine-mediated vasodilation in epineurial arterioles of the sciatic nerve compared to nontreated diabetic rats. Treating diabetic rats with 0.25% α-lipoic acid and fidarestat (3 mg/kg body weight) was equally or more effective in preventing vascular and neural dysfunction than was monotherapy of diabetic rats with higher doses of α-lipoic acid or fidarestat. Treating diabetic rats with the combination of 0.25% α-lipoic acid and fidarestat (3 mg/kg body weight) significantly improved several markers of oxidative stress and increased the serum levels of both α-lipoic acid and dihydrolipoic acid. These studies suggest that combination therapy consisting of α-lipoic acid and fidarestat may be more efficacious in preventing diabetes-induced vascular and neural dysfunction in peripheral tissue compared to monotherapy, which requires higher doses to be equally effective. The effect of this combination therapy may in part be due to the increased production and/or level of dihydrolipoic acid.     

Evidence for two distinct mechanisms of resistance in the rat to reinfection with Fasciola hepatica

Doy T. G. and Hughes D. L. 1982. Evidence for two distinct mechanisms of resistance in the rat to reinfection with Fasciola hepatica. International Journal for Parasitology12: 357–361. Congenitally athymic nude (rnu/rnu) and heterozygous hairy (rnu/ + ) rats were found to be equally highly resistant to oral reinfection with Fasciola hepatica. Accompanying the development of this resistance was a marked increase in intestinal eosinophil numbers. The sensitised rnu/ + rats showed a similar marked resistance to intraperitoneal challenge with newly excysted juvenile (NEJ) flukes. This was much less effective in the rnu/rnu rats, although there was some evidence of reduced numbers and stunting of parasites. Serum from infected rnu/rnu rats, unlike that from the infected rnu/+ rats, failed to induce the adherence of eosinophils to NEJ flukes in vitro. Flukes recovered from rnu/rnu rats were in general considerably larger than comparable flukes from their rnu/ + counterparts.There thus appears to be two distinct mechanisms of resistance to reinfection with F. hepatica operating in the rat. The first a T-independent system effective at the gut wall and the second, effective after penetration of the gut and requiring a T-dependent response for full expression. If eosinophils are involved in protection they can apparently function in the gut wall in the absence of an adherence promoting antibody in the serum.     

Immunological response of the rat to infection with Taenia taeniaeformis: protective antibody response to implanted parasites.

Intraperitoneally implanted metacestodes of either T. taeniaeformis or T. crassiceps in rats provoked a high degree of resistance to oral challenge with eggs of T. taeniaeformis. This resistance was passively transferred to normal recipients with serum. Immunoglobulin fractions of immune serum containing IgG₁ or IgM were most effective in passive transfer and little activity was associated with IgG₂ antibodies. No skin-sensitizing antibodies were detectable in immune sera. These findings are in sharp contrast to previous observations involving protective immunoglobulins and reaginic antibodies in serum from rats with hepatic cysticerci of T. taeniaeformis. Possible reasons for this are discussed. Cysticerci implanted into normal rats survived for at least 21 days with no sign of host rejection, whereas those implanted into rats with hepatic infections with T. taeniaeformis were killed and encapsulated. Similar results were obtained by implanting cysticerci in normal rats given inoculations of complete Freund's adjuvant. Repeated inoculations of immune serum had no effect on the survival of implanted cysticerci, and it was concluded that exposure to infection by oncospheres provokes cellular defense mechanisms which can be effective against cysticerci in abnormal sites. Why these mechanisms are inoperative against hepatic cysticerci remains unclear.     

Trypanosoma brucei: An evaluation of salicylhydroxamic acid as a trypanocidal drug

The chemotherapeutic potential of salicylhydroxamic acid (SHAM) was studied in adult rats infected with a strain of Trypanosoma brucei that kills the rats in about 100 hr. The median lethal dose, administered intraperitoneally in a carboxymethyl-cellulose suspension, is approximately 820 mg/kg body weight for male and 850 mg/kg for female rats. The apparent cause of death is severe depression of the central nervous system.Half-maximal inhibition of O₂ uptake by trypanosomes in vitro requires 15 μM SHAM, whereas 100 μM inhibits over 90%. This inhibitory effect on trypanosome respiration was used as a biological assay for the effective SHAM concentration in rat plasma. After administration of a sublethal SHAM dose to rats, the effective plasma SHAM concentration rose rapidly to about 500 μM and then fell to about 10 μM at 4 hr. Nevertheless, this dose did not significantly affect the survival time of rats infected with T. brucei. Even if, by repeated SHAM administration, the plasma SHAM concentration was kept at around 100 μM for more than 4 hr, no therapeutic effect was observed.These results show that O₂ uptake is not essential for the survival of trypanosomes in rats and they support the idea that bloodstream trypanosomes have an alternative pathway for glycolysis, allowing energy production in the absence of respiration.The possibility that SHAM or other inhibitors of trypanosome respiration could stilll be trypanocidal if used in conjunction with another inhibitor of glycolysis is discussed.     

Urban rat exposure to anticoagulant rodenticides and zoonotic infection risk

Anticoagulant rodenticides (ARs) deployed to control rodent pest populations can increase the risk of pathogen infection for some wildlife. However, it is unknown whether ARs also increase infection risk for target rodents, which are common hosts for zoonotic (animal-to-human transmitted) pathogens. In this study, we tested whether rats exposed to ARs were more likely to be infected with zoonotic pathogens, specifically Leptospira spp. or Escherichia coli, after controlling for known predictors of infection (i.e. sex, age, body condition). We collected biological samples from 99 rats trapped in Chicago alleys and tested these for Leptospira infection, E. coli shedding and AR exposure. We found that rats that had been exposed to ARs and survived until the time of trapping, as well as older rats, were significantly more likely to be infected with Leptospira spp. than other rats. We found no significant association between E. coli shedding and any predictors. Our results show that human actions to manage rats can affect rat disease ecology and public health risks in unintended ways, and more broadly, contribute to a growing awareness of bidirectional relationships between humans and natural systems in cities.     

The bioactive alkaloids identified from Cortex Phellodendri ameliorate benign prostatic hyperplasia via LOX-5/COX-2 pathways

BackgroundThe bioactive alkaloids identified from Cortex Phellodendri (CP) were highly effective in treating rats with benign prostatic hyperplasia (BPH). Specifically, lipoxygenase-5 (LOX-5) and cyclooxygenase-2 (COX-2) were identified as two primary targets for alleviating inflammation in BPH rats. However, it remains unknown whether the alkaloid components in CP can interact with the two target proteins.PurposeTo further identify bioactive alkaloids targeting LOX/COX pathways.MethodsAn affinity-ultrafiltration mass spectrometry approach was employed to screen dual-target LOX-5/COX-2 ligands from alkaloid extract. The structures of bioactive alkaloids were characterized by high-resolution Fourier transform ion cyclotron resonance mass spectrometry. To understand the molecular mechanisms underlying the effects of bioactive alkaloids, the expression levels of LOX-5 and COX-2 in BPH model rats were investigated at both protein and mRNA levels. The LOX-5/COX-2 enzymes activity experiments and molecular docking analysis were performed to fully evaluate the interactions between bioactive alkaloids and LOX-5/COX-2.ResultsAfter comprehensive analysis, the results showed that bioactive alkaloids could suppress the expression of LOX-5 and COX-2 simultaneously to exert an anti-inflammatory effect on the progression of BPH. In addition, the screened protoberberine, demethyleneberberine was found to exhibit prominent inhibitory activities against both LOX-5 and COX-2 enzymes, palmatine and berberine with moderate inhibitory activities. Molecular docking analysis confirmed that demethyleneberberine could interact well with LOX-5/COX-2.ConclusionThis study is the first to explore the inhibitory effects of bioactive alkaloids from CP on LOX-5 and COX-2 activities in BPH rats. Our findings demonstrate that the bioactive alkaloids from CP can ameliorate BPH via dual LOX-5/COX-2 pathways, which serves as an efficient approach for the discovery of novel drug leads from natural products with reduced side effects.     

The possible protective and therapeutic effects of ginger and cinnamon on the testis and coda epididymis of streptozotocin-induced-diabetic rats: Histological and biochemical studies

Diabetes mellitus (DM) is a metabolic condition characterized by high blood sugar levels with serious system complications. Ginger (Zingiber officinale) and Cinnamon (Cinnamomum zeylanicum) have anti-diabetic activities. The goal of this study is to evaluate the possible protective and therapeutic effects of ginger and Cinnamon against histological, Ki67 Immunohistochemistry (IHC) and biochemical studies in testis and coda epididymis of Streptozotocin (STZ) induced diabetic rats. The experimental rats were divided into six groups: G1 was the control, G2 induced diabetic without treatment, G3 was treated with ginger before induction of DM (ginger protective), G4 were given ginger after DM induction (ginger therapeutic), G5 were given cinnamon before induction of DM (cinnamon protective) and G6 were given cinnamon after DM induction (cinnamon therapeutic). In diabetic rats’ significant increases in fasting blood sugar and body weight were observed after three weeks. Ginger and cinnamon effectively decreased serum glucose levels. Histopathological evaluations of seminiferous tubules and coda epididymis sections from diabetic rats showed severe damage to them. Furthermore, the sections of seminiferous tubules and coda epididymis rats administered ginger and cinnamon extract showed normal structure, healthy lining epithelium and sperm contents compared to diabetic rats. The results of the study show that both Ginger and Cinnamon aqueous extracts are effective as both hypoglycemic natural supplements that can protect against diabetic-induced testicular damage as well as share in the reservation of the cauda epididymal structure and sperm contents.     

Effect of Lower Doses of Vanadate in Combination with Azadirachta indica Leaf Extract on Hepatic and Renal Antioxidant Enzymes in Streptozotocin-Induced Diabetic Rats

The present study was undertaken to investigate short-term (21 days) effects of oral administration of Azadirachta indica leaf extract and vanadate, separately and in combination, on the activities of antioxidant enzymes in streptozotocin-induced diabetic rats. Vanadate is a remarkable antidiabetic agent and shows insulin mimetic effect. However, severe toxicity is associated with vanadate when used in high concentration while at lower concentration the hypoglycemic property of vanadate is reduced. So, we used a low dose of vanadate in combination with A. indica leaf extract and evaluated their effect on the antioxidant defense system. Streptozotocin-diabetic rats were treated separately with insulin, vanadate (0.6 mg/ml), A. indica, and with combined dose of vanadate (0.2 mg/ml) and A. indica. At the end of the experiment, rats were sacrificed and serum glucose levels and activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were determined in cytosolic fraction of liver and kidney. Diabetic rats showed hyperglycemic condition and alteration in antioxidant enzyme activities. Treatment with antidiabetic compounds resulted in the reduction of glucose levels and restoration of enzyme activities to normal. Results showed that combined treatment of vanadate and A. indica leaf extract was the most effective in normalizing altered antioxidant enzyme system.     

Generation of Rat-Induced Pluripotent Stem Cells from a New Model of Metabolic Syndrome

We recently characterized DahlS.Z-Lepr^fa/Lepr^fa (DS/obese) rats, derived from a cross between Dahl salt-sensitive rats and Zucker rats, as a new animal model of metabolic syndrome (MetS). Although the phenotype of DS/obese rats is similar to that of humans with MetS, the pathophysiological and metabolic characteristics in each cell type remain to be clarified. Hence, the establishment of induced pluripotent stem cells (iPSCs) derived from MetS rats is essential for investigations of MetS in vitro. Reports of rat iPSCs (riPSCs), however, are few because of the difficulty of comparing to other rodents such as mouse. Recently, the advantage of using mesenchymal stromal cells (MSCs) as a cell source for generating iPSCs was described. We aimed to establish riPSCs from MSCs in adipose tissues of both DS/obese rats and their lean littermates, DahlS.Z-Lepr⁺/Lepr⁺ (DS/lean) rats using lentivirus vectors with only three factors Oct4, Klf4, and Sox2 without c-Myc. The morphology, gene expression profiles, and protein expression of established colonies showed embryonic stem cell (ESCs)-like properties, and the differentiation potential into cells from all three germ layers both in vitro and in vivo (teratomas). Both riPSCs became adipocytes after induction of adipogenesis by insulin, T3, and dexamethasone. Real-time PCR analysis also revealed that both riPSCs and the adipose tissue from DS/obese and DS/lean rats possess similar expression patterns of adipocyte differentiation-related genes. We succeeded in generating riPSCs effectively from MSCs of both DS/obese and DS/lean rats. These riPSCs may well serve as highly effective tools for the investigation of MetS pathophysiology in vitro.     

Rodent-Borne <Emphasis Type="Italic">Bartonella</Emphasis> Infection Varies According to Host Species Within and Among Cities

It is becoming increasingly likely that rodents will drive future disease epidemics with the continued expansion of cities worldwide. Though transmission risk is a growing concern, relatively little is known about pathogens carried by urban rats. Here, we assess whether the diversity and prevalence of Bartonella bacteria differ according to the (co)occurrence of rat hosts across New Orleans, LA (NO), where both Norway (Rattus norvegicus) and roof rats (Rattus rattus) are found, relative to New York City (NYC) which only harbors Norway rats. We detected human pathogenic Bartonella species in both NYC and New Orleans rodents. We found that Norway rats in New Orleans harbored a more diverse assemblage of Bartonella than Norway rats in NYC and that Norway rats harbored a more diverse and distinct assemblage of Bartonella compared to roof rats in New Orleans. Additionally, Norway rats were more likely to be infected with Bartonella than roof rats in New Orleans. Flea infestation appears to be an important predictor of Bartonella infection in Norway rats across both cities. These findings illustrate that pathogen infections can be heterogeneous in urban rodents and indicate that further study of host species interactions could clarify variation in spillover risk across cities.     

The acute effects of single-dose orally administered doramectin, eprinomectin and selamectin on natural infections of Syphacia muris in rats

This study was designed to determine the acute effects of a single-dose of orally administered doramectin, eprinomectin and selamectin on Syphacia muris infection in rats. Rats, naturally infected with S. muris, were divided into four groups: three different treatment groups (n = 7) and one positive control (n = 7). Cellophane tape preparations were obtained from the treated rats on day 0 pre-treatment and on days 2, 4 and 6 post-treatment. Syphacia sp. eggs were counted. Eprinomectin was found to be 100% effective in eliminating eggs on two post-treatment. However when egg counts on day 6 post-treatment were compared with pre-treatment egg counts, doramectin and selamectin were found to be 99.32 and 98.77% effective in eliminating eggs, respectively. On day 7 post-treatment, blood samples were obtained from all groups, and then the rats were necropsied. Doramectin, eprinomectin and selamectin were found to be 100% effective in eliminating adult S. muris, when compared with the positive control group.     

Effect of Shuangjinlian mixture on oral ulcer model in rat

ObjectiveTo observe the effect of common clinical drug Shuangjin Lian mixture on rats with oral ulcer and discuss its mechanism.MethodsSodium carboxymethyl cellulose caused leukocyte aggregation in rats, observed the anti-inflammatory effect of Shuangjin mixture. 3 mm * 3 mm size ulcer surface in the oral cavity of rats was caused by 90% phenol solution, to observe the therapeutic effect and anti-inflammatory effect of Shuangjinlian mixture on rats with oral ulcers.ResultThe low, middle and high dose Shuangjinlian mixture can inhibits the accumulation of white blood cells caused by sodium carboxymethyl cellulose in rats significantly (P < 0.01). And reduce the degree of edema and hyperaemia around the ulcer tissue significantly (P < 0.01), improve the ulcer healing probability, and reduce the level of TNF-α, VEGF levels and increase IL-2 level in the serum of rats with oral ulcers significantly (P < 0.01). Pathological examination showed that the lesion of ulcer tissue in each treatment group was obviously alleviated.ConclusionShuangjinlian mixture had anti-inflammatory effect and was effective for the prevention and treatment of oral ulcer in rats.     

Pancreatic Alpha-Cell Dysfunction Contributes to the Disruption of Glucose Homeostasis and Compensatory Insulin Hypersecretion in Glucocorticoid-Treated Rats

Glucocorticoid (GC)-based therapies can cause insulin resistance (IR), glucose intolerance, hyperglycemia and, occasionally, overt diabetes. Understanding the mechanisms behind these metabolic disorders could improve the management of glucose homeostasis in patients undergoing GC treatment. For this purpose, adult rats were treated with a daily injection of dexamethasone (1 mg/kg b.w., i.p.) (DEX) or saline as a control for 5 consecutive days. The DEX rats developed IR, augmented glycemia, hyperinsulinemia and hyperglucagonemia. Treatment of the DEX rats with a glucagon receptor antagonist normalized their blood glucose level. The characteristic inhibitory effect of glucose on glucagon secretion was impaired in the islets of the DEX rats, while no direct effects were found on α-cells in islets that were incubated with DEX in vitro. A higher proportion of docked secretory granules was found in the DEX α-cells as well as a trend towards increased α-cell mass. Additionally, insulin secretion in the presence of glucagon was augmented in the islets of the DEX rats, which was most likely due to their higher glucagon receptor content. We also found that the enzyme 11βHSD-1, which participates in GC metabolism, contributed to the insulin hypersecretion in the DEX rats under basal glucose conditions. Altogether, we showed that GC treatment induces hyperglucagonemia, which contributes to an imbalance in glucose homeostasis and compensatory β-cell hypersecretion. This hyperglucagonemia may result from altered α-cell function and, likely, α-cell mass. Additionally, blockage of the glucagon receptor seems to be effective in preventing the elevation in blood glucose levels induced by GC administration.     

Bauhinia forficata Prevents Vacuous Chewing Movements Induced by Haloperidol in Rats and Has Antioxidant Potential In Vitro

Classical antipsychotics can produce motor disturbances like tardive dyskinesia in humans and orofacial dyskinesia in rodents. These motor side effects have been associated with oxidative stress production in specific brain areas. Thus, some studies have proposed the use of natural compounds with antioxidant properties against involuntary movements induced by antipsychotics. Here, we examined the possible antioxidant activity of Bauhinia forficata (B. forficata), a plant used in folk medicine as a hypoglycemic, on brain lipid peroxidation induced by different pro-oxidants. B. forficata prevented the formation of lipid peroxidation induced by both pro-oxidants tested. However, it was effective against lipid peroxidation induced by sodium nitroprusside (IC₅₀ = 12.08 μg/mL) and Fe²⁺/EDTA (IC₅₀ = 41.19 μg/mL). Moreover, the effects of B. forficata were analyzed on an animal model of orofacial dyskinesia induced by long-term treatment with haloperidol, where rats received haloperidol each 28 days (38 mg/kg) and/or B. forficata decoction daily (2.5 g/L) for 16 weeks. Vacuous chewing movements (VCMs), locomotor and exploratory activities were evaluated. Haloperidol treatment induced VCMs, and co-treatment with B. forficata partially prevented this effect. Haloperidol reduced the locomotor and exploratory activities of animals in the open field test, which was not modified by B. forficata treatment. Our present data showed that B. forficata has antioxidant potential and partially protects against VCMs induced by haloperidol in rats. Taken together, our data suggest the protection by natural compounds against VCMs induced by haloperidol in rats.     

Non-intrusive systematic study reveals mutualistic interactions between threatened island endemic species and points to more impactful conservation

Oceanic islands harbour a disproportionately large share of extinct and endangered birds worldwide and up to about 6,800 highly threatened plants, stressing the urgency for conservation efforts there. However, effective conservation action can only be as sound as the ecological understanding on which it is based. Knowledge about the ecology of threatened birds and plants can be relatively sketchy even in well-studied oceanic islands and this can potentially misdirect or erode conservation actions’ effectiveness. We used camera traps to document vertebrate flower visitors of a threatened, mono-specific endemic oceanic island plant (Roussea simplex) that produces much nectar and which was abundant until the 1930s before declining severely despite its presence mostly within protected areas. We determined proportions of native and alien flower visitors in four populations and characterised their ecological role (e.g. florivore, nectar robber, pollinator) through observations and exclusion experiments alongside experiments to determine seed sets by agamospermy, autogamy, geitonogamy and xenogamy. Five native and three alien vertebrate species visited flowers (N = 5,085 camera trap-hours), 96.6% of visits being from birds. Among endemics, 74–96% of visits were by the Mauritius Bulbul (Hypsipetes olivaceus), a threatened bird able to effect pollination contrary to the other endemic birds. Roussea simplex is primarily xenogamous, producing 2,657 ± 480 seeds, and seed set dropped markedly when the bird was excluded (861.8 ± 91.0 SE, Kruskal-Wallis χ² = 14.2, p < 0.001). Natural seed set was very low (410.0 ± 85.3 SE) where the bird was locally extinct or very rare. Invasive alien rats (Rattus rattus) and long-tailed macaques (Macaca fascicularis) were important florivores or nectar robbers. Systematic non-intrusive study using camera traps combined with manipulative experiments revealed a mutualism between two relatively well-studied threatened endemic species as well as new threats from alien vertebrates acting as nectar robbers and florivores. Roussea simplex’s major decline within protected areas and its abundant and year round flowering and nectar production point to a major hitherto unrecorded drop in floral resource previously available to at least five endemic species, and particularly to its commonest flower visitor and principal pollinator, the threatened Mauritius Bulbul. These findings exemplify how systematic non-intrusive study of threatened species may radically change conservation managers’ priorities which in the current case should focus primarily on controlling alien rats and macaques and re-instating or reinforcing Bulbul-Roussea mutualism as each would be more impactful than addressing gecko-Roussea mutualism disruption by alien ants which so far was the only recorded threat thought to drive the rapid decline of Roussea simplex. Our study underscores that current conservation efforts should also pay particular attention to medium to longer-term changes in habitat or community composition which may not be obvious from merely considering extent and composition of current habitats.     

Exaggerated Acute Lung Injury and Impaired Antibacterial Defenses During Staphylococcus aureus Infection in Rats with the Metabolic Syndrome

Rats with Metabolic Syndrome (MetaS) have a dysregulated immune response to the aseptic trauma of surgery. We hypothesized that rats with MetaS would have dysregulated inflammation, increased lung injury, and less effective antibacterial defenses during Staphylococcus (S.) aureus sepsis as compared to rats without MetaS. Low capacity runner (LCR; a model of MetaS) and high capacity runner (HCR) rats were challenged intravenously with S. aureus bacteria. After 48 h, inflammatory mediators and bacteria were quantified in the blood, bronchoalveolar lavage fluid (BALF), and lung homogenates. Lungs were analyzed histologically. BALF protein and lung wet-dry ratios were quantified to assess for vascular leak. Endpoints were compared in infected LCR vs HCR rats. LCR rats had higher blood and lung S. aureus counts, as well as higher levels of IL-6 in plasma, lungs and BALF, MIP-2 in plasma and lung, and IL-17A in lungs. Conversely, LCR rats had lower levels of IL-10 in plasma and lungs. Although lactate levels, and liver and renal function tests were similar between groups, LCR rats had higher BALF protein and lung wet-dry ratios, and more pronounced acute lung injury histologically. During S. aureus bacteremia, as compared with HCR rats, LCR (MetaS) rats have heightened pro-inflammatory responses, accompanied by increased acute lung injury and vascular leak. Notably, despite an augmented pro-inflammatory phenotype, LCR rats have higher bacterial levels in their blood and lungs. The MetaS state may exacerbate lung injury and vascular leak by attenuating the inflammation-resolving response, and by weakening antimicrobial defenses.     

Competition for dietary fructose between Moniliformis (acanthocephala) and growing rats

Crompton D. W. T., Singhvi A., Nesheim M. C. and Walters D. E. 1981. Competition for dietary fructose between Moniliformis (Acanthocephala) and growing rats. International journal for Parasitology11: 457–461. The food intake, weight gain and blood sugar of young rats, fed on diets containing growth-limiting amounts of fructose and infected with Moniliformis dubius (Acanthocephala) for 6 weeks, were measured and compared with values obtained from similar uninfected rats which had been treated in the same manner. The growth of the rats was closely related to the fructose content of the diet. However, on average, the infected rats gained less weight than their uninfected counterparts. Significant differences between the values for blood sugar from infected and uninfected rats were not detected when the diet contained 2% fructose. The blood sugar of infected rats fed on a diet containing 4% fructose was found to be significantly less than that of similar uninfected rats. Information was also obtained about the numbers, sex, dry weight and location of the Moniliformis in the small intestines of their hosts. Male and female Moniliformis from rats fed on the 4% fructose diet were found to be heavier than those from rats fed on the 2% fructose diet. The results can be interpreted to suggest that the reduction in the growth rate of the infected rats is due to competition for fructose between Moniliformis and the rat.     

Mixed Infections, Cryptic Diversity, and Vector-Borne Pathogens: Evidence from Polygenis Fleas and Bartonella Species

Coinfections within hosts present opportunities for horizontal gene transfer between strains and competitive interactions between genotypes and thus can be a critical element of the lifestyles of pathogens. Bartonella spp. are Alphaproteobacteria that parasitize mammalian erythrocytes and endothelial cells. Their vectors are thought to be various biting arthropods, such as fleas, ticks, mites, and lice, and they are commonly cited as agents of various emerging diseases. Coinfections by different Bartonella strains and species can be common in mammals, but little is known about specificity and coinfections in arthropod vectors. We surveyed the rate of mixed infections of Bartonella in flea vectors (Polygenis gwyni) parasitizing cotton rats (Sigmodon hispidus) in which previous surveys indicated high rates of infection. We found that nearly all fleas (20 of 21) harbored one or more strains of Bartonella, with rates of coinfection approaching 90%. A strain previously identified as common in cotton rats was also common in their fleas. However, another common strain in cotton rats was absent from P. gwyni, while a rare cotton rat strain was quite common in P. gwyni. Surprisingly, some samples were also coinfected with a strain phylogenetically related to Bartonella clarridgeiae, which is typically associated with felids and ruminants. Finally, a locus (pap31) that is characteristically borne on phage in Bartonella was successfully sequenced from most samples. However, sequence diversity in pap31 was novel in the P. gwyni samples, relative to other Bartonella previously typed with pap31, emphasizing the likelihood of large reservoirs of cryptic diversity in natural populations of the pathogen.     

Deposition of docosahexaenoic acid (DHA) is limited in forebrain of young obese fa/fa Zucker rats fed a diet high in α-linolenic acid but devoid of DHA

Docosahexaenoic acid (DHA) is required for neurotransmitter synthesis and learning. Conversion of α-linolenic acid (ALA) to DHA is considered adequate to support brain function in youth, but it is unknown if brain DHA can be maintained in insulin resistant states. This study investigated brain fatty acid and desaturase activities in young insulin resistant Zucker rats on diets with and without DHA. Male fa/fa and lean rats were fed diets enriched with flaxseed (FXO, ALA: 35.5% fatty acids), menhaden (MO, DHA: 9.2%) or safflower oil (SO, linoleic acid: 54.1%) for 9 weeks, n=8 per diet per genotype. Compared to lean, the 15 week old fa/fa rats were obese (56% heavier) and insulin-resistant (>18-fold in homeostasis model assessment of insulin resistance). The forebrain of fa/fa rats had higher palmitoleic (16:1n-7) and dihomo-γ-linolenic (20:3n-6) acids, and higher Δ9, Δ6 but lower Δ5 (all P≤.006) desaturase indices than lean. The Δ9 and Δ6 desaturase indices positively, while the Δ5 negatively (all P≤.01) correlated with insulin resistance. The Δ9 desaturase index positively correlated with adiposity index. The percentage of forebrain DHA of fa/fa rats was lower (P=.011) than lean rats when fed FXO diet while there was no difference (P>.05) between fa/fa and lean rats fed MO or SO diet. Thus, the alterations in the fatty acid and desaturase indices in the brain were consistent inhibited forebrain synthesis of DHA in the fa/fa rats. ALA may not have potential to effectively serve as a precursor for synthesizing DHA for youth forebrain during insulin resistance since Δ5 desaturase activity is limited.     

Interstitial pneumonia in immunocompetent laboratory rats caused by natural infection with Pneumocystis carinii

Pneumocystis (P.) carinii is known to cause fatal pneumonia in immunocompromised rats. Cases of P. carinii interstitial pneumonia in immunocompetent rats have been shown histologically to present with perivascular lymphoid cuffs, which have previously been attributed to rat respiratory virus. This study aims to determine the prevalence and pathological characteristics of P. carinii in immunocompetent laboratory rats in experimental facilities in Japan. An epidemiological survey for this agent was performed using PCR to assess 1,981 immunocompetent rats from 594 facilities in Japan. We observed that 6 of the 1,981 rats (0.30%) from 4 out of 594 facilities (0.67%) were positive for P. carinii without infection of other known pathogens. Gross pulmonary lesions were found in 4 of the 6 affected rats. The lungs of these rats contained scattered dark red/gray foci. Histopathologically, the lungs exhibited interstitial pneumonia with lymphoid perivascular cuffs: Pneumocystis cysts were observed using Grocott’s methenamine silver stain. To our knowledge, this report is the first to reveal the prevalence of natural P. carinii infection in immunocompetent laboratory rats in Japan.