Uninfected Rats Research Articles

Toxicological evaluation of anti-cough herbal tea made from aqueous extracts of G. Kola, C. Citratus and B. pinnatum

Background: Herbal formulations currently contribute significantly to medical remedies with varying effects on health indices. Garcinia kola seeds, Cymbapogon citratus, and Bryophyllum pinnantum leaves are among the widely used in herbal formulations. Objectives: This study evaluated the toxicological effects of the ternary combination of these plant materials on some renal, hepatic, hematological and histological parameters of streptococci-infected white albino rats. Materials and Methods: Samples of Garcinia kola seeds, Cymbapogon citratus leaves, and Bryophyllum pinnantum leaves were sourced locally and authenticated by a taxonomist. Aqueous extract of the ternary combination comprising of 40% G. kola, 30% C. citratus, and 30% B. pinnantum was prepared and administered on albino rats. Thirty five white albino rats grouped into 7 groups comprising of normal control, treatment control, disease control, and test group were used for the evaluation after a 14 days treatment on infected and uninfected rats. The rats were sacrificed, and samples collected. Some renal, hepatic, histological, and hematological indices were analyzed. Results: Comparison of all hematological parameters (except for platelet count) between uninfected-untreated and unifected-treated with extract showed no significant (p>0.05) difference. Platelet count was significantly (p<0.05) raised in all groups treated with the extract. Comparison control and the extract-treated group showed no significant (p>0.05) difference in renal parameters indicating no adverse effects on renal function. However, comparison of parameters between control and the infected-treated group showed significantly elevated creatinine which alone may not be sufficient to support renal damage. Albumin, and total bilirubin were significantly (p<0.05) lower in the extract-treated group compared to the control group. In contrast, total protein and globulin were significantly (p<0.05) higher in the controls to the infected groups. ALT and AST were significantly (p<0.05) lower in the extract treated groups compared to the control group. Although comparison of ALP activity between uninfected-untreated and infected-treated group showed significant (p<0.05) elevation this alone may not be sufficient to support liver damage. The hematoxyline and eosine stained sections of the kidney and the liver tissues of the tea fed groups show normal kidney and liver histology. There was no significant change in the liver and kidney histology of the test and control groups. The extract did not cause adverse impact on these organs. Conclusion: Ternary combination of 40% G. kola, 30% C. citratus, and 30% B. pinnantum can effectively be used in treatment of cough without significant adverse effects on renal, hepatic, hematological and histological parameters. The ternary combination rather demonstrated significant hepato-protective feature.

Clove flower extracts (Syzgium aromaticum) increased incision wound epithelization, platelet count, and TGF-β levels in methicillin-resistant Staphylococcus aureus-infected rats

Background: The wound healing process consists of three phases, namely inflammation, proliferation, and remodeling. Many cells and mediators are involved in this process, including platelets and transforming growth factor-β (TGF-β). Methicillin-resistant Staphylococcus aureus (MRSA) is a bacterial strain resistant to beta-lactam antibiotics. Clove flower (Syzygium aromaticum) is an herb with properties to promote wound healingObjective: To determine the effect of clove flower extract on increasing epithelialization of incision wounds, platelet counts, and TGF-β levels in mice infected with MRSAMethods: A randomized experimental study on 30 male wistar rats (Rattus norvegicus) infected with MRSA. All rats were randomly divided into six groups; healthy control, positive control induced by MRSA and Vancomycin 9 mg/200 gram body weight (gbw), negative control MRSA with normal saline, and administration of clove flower extract (CFE) 25 mg/200 gbw, CFE 50 mg/200 gbw, and CFE 100 mg/200 gbw. Examination of the sectioned wound epithelium was performed histologically using Hematoxylin-Eosin (HE), while platelet count and TGF-β levels were measured using an ELISA RAB0479 kit simultaneously on the 21st day. Results: Histological examination of rats treated with CFE 100 mg/200 gbw and uninfected rats showed complete epithelization. Platelet counts and TGF-β levels were significantly higher in rats administered CFE 100 mg/200 gbw (p<0.001) compared to the other five groups. Conclusion: Administrating CFE increased incision wound epithelialization, platelet count, and TGF-β levels in MRSA-infected rats.

Latent toxoplasmosis impairs learning and memory yet strengthens short-term and long-term hippocampal synaptic plasticity at perforant pathway-dentate gyrus, and Schaffer collatterals-CA1 synapses

Investigating long-term potentiation (LTP) in disease models provides essential mechanistic insight into synaptic dysfunction and relevant behavioral changes in many neuropsychiatric and neurological diseases. Toxoplasma (T) gondii is an intracellular parasite causing bizarre changes in host’s mind including losing inherent fear of life-threatening situations. We examined hippocampal-dependent behavior as well as in vivo short- and long-term synaptic plasticity (STP and LTP) in rats with latent toxoplasmosis. Rats were infected by T. gondii cysts. Existence of REP-529 genomic sequence of the parasite in the brain was detected by RT-qPCR. Four and eight weeks after infection, spatial, and inhibitory memories of rats were assessed by Morris water maze and shuttle box tests, respectively. Eight weeks after infection, STP was assessed in dentate gyrus (DG) and CA1 by double pulse stimulation of perforant pathway and Shaffer collaterals, respectively. High frequency stimulation (HFS) was applied to induce LTP in entorhinal cortex-DG (400 Hz), and CA3-CA1 (200 Hz) synapses. T. gondii infection retarded spatial learning and memory performance at eight weeks post-infection period, whereas inhibitory memory was not changed. Unlike uninfected rats that normally showed paired-pulse depression, the infected rats developed paired-pulse facilitation, indicating an inhibitory synaptic network disruption. T. gondii-infected rats displayed strengthened LTP of both CA1-pyramidal and DG-granule cell population spikes. These data indicate that T. gondii disrupts inhibition/excitation balance and causes bizarre changes to the post-synaptic neuronal excitability, which may ultimately contribute to the abnormal behavior of the infected host.

Dual effects of NV-CoV-2 biomimetic polymer: An antiviral regimen against COVID-19.

Remdesivir (RDV) is the only antiviral drug approved for COVID-19 therapy by the FDA. Another drug LAGEVRIO™ (molnupiravir) though has not been approved yet by FDA but has been authorized on December 23, 2021, for emergency use to treat adults with mild-to moderate COVID-19 symptoms and for whom alternative COVID-19 treatment options are not clinically appropriate. The fact is that the efficacy of RDV is, however, limited in vivo though it is highly promising in vitro against SARS-CoV-2 virus. In this paper we are focusing on the action mechanism of RDV and how it can be improved in vivo. The stability of RDV alone and on encapsulation with our platform technology based polymer NV-387 (NV-CoV-2), were compared in presence of plasma in vitro and in vivo. Furthermore, a non-clinical pharmacology study of NV-CoV-2 (Polymer) and NV CoV-2 (Polymer encapsulated Remdesivir) in both NL-63 infected and uninfected rats was done. In addition, the antiviral activity of NV-CoV-2 and NV-CoV-2-R was compared with RDV in a cell culture study. The results are (i) NV-CoV-2 polymer encapsulation protects RDV from plasma-mediated catabolism in both in vitro and in vivo, studies; (ii) Body weight measurements of the normal (uninfected) rats after administration of the test materials (NV-CoV-2 and NV-CoV-2-R) showed no toxic effects. (iii) Body weight measurements and survival rates of the NL-63 infected rats were similar to the uninfected rats after treatment with NV-CoV-2 and NV-CoV-2-R. Overall, the efficacy as an antiviral regimens were found in this order as below; NV-CoV-2-R > NV-CoV-2 > RDV. Our platform technology based NV-387-encapsulated-RDV (NV-CoV-2-R) drug has a dual effect against different variants of the coronaviruses. First, NV-CoV-2 is an antiviral regimen. Secondly, RDV is protected from plasma-mediated degradation in transit. All together, NV-CoV-2-R is the safest and efficient regimen against COVID-19.

Novel 1,2,3-Triazole-sulphadiazine-ZnO Hybrids as Potent Antimicrobial Agents against Carbapenem Resistant Bacteria.

Bacterial pneumonia is considered one of the most virulent diseases with high morbidity and mortality rates, especially in hospitalized patients. Moreover, bacterial resistance increased over the last decades which limited the therapy options to carbapenem antibiotics. Hence, the metallo-β-lactamase-producing bacteria were deliberated as the most deadly and ferocious infectious agents. Sulphadiazine-ZnO hybrids biological activity was explored in vitro and in vivo against metallo-β-lactamases (MBLs) producing Klebsiella pneumoniae. Docking studies against NDM-1 and IMP-1 MBLs revealed the superior activity of the 3a compound in inhibiting both MBLs enzymes in a valid reliable docking approach. The MBLs inhibition enzyme assay revealed the remarkable sulphadiazine-ZnO hybrids inhibitory effect against NDM-1 and IMP-1 MBLs. The tested compounds inhibited the enzymes both competitively and noncompetitively. Compound 3b-ZnO showed the highest antibacterial activity against the tested metallo-β-lactamase producers with an inhibition zone (IZ) diameter reaching 43 mm and a minimum inhibitory concentration (MIC) reaching 2 µg/mL. Sulphadiazine-ZnO hybrids were tested for their in vitro cytotoxicity in a normal lung cell line (BEAS-2Bs cell line). Higher cell viability was observed with 3b-ZnO. Biodistribution of the sulphadiazine-ZnO hybrids in the lungs of uninfected rats revealed that both [124I]3a-ZnO and [124I]3b-ZnO hybrids remained detectable within the rats’ lungs after 24 h of endotracheal aerosolization. Moreover, the residence duration in the lungs of [124I]3b-ZnO (t1/2 4.91 h) was 85.3%. The histopathological investigations confirmed that compound 3b-ZnO has significant activity in controlling bacterial pneumonia infection in rats.

Differences in microbiome of healthy Sprague Dawley rats with Paragonimus proliferus infection and potential pathogenic role of microbes in paragonimiasis

Paragonimiasis, which is caused by Paragonimus, is considered to be a neglected tropical disease by the World Health Organization. The pathogenicity of Paragonimus mainly manifests as mechanical damage and immunotoxicity caused by adult worms and larvae. However, microbiota associated with Paragonimus and potential disturbance of host microbiota after infection are unknown. Paragonimus proliferus is a rare species, and its successful infection rate in experimental rats is 100%. In the current study, we compared the microbial community in lung tissues, small intestine contents, and fecal samples from Sprague Dawley (SD) rats with and without P. proliferus infection. To determine the impact of P. proliferus on the microbial community in rats, we identified the microbiota in adult worms of P. proliferus via high-throughput sequencing. Results showed dramatic differences in the composition of microbiota in lung tissues between infected and uninfected rats. Paragonimus metacercariae introduced both environmental and gut microbes into the lung tissues of rats. Many potentially pathogenic microbes were also found in the lung of infected rats. Paragonimus infection increased the chances of potentially pathogenic microbiota invading and colonizing the lungs. However, for the purpose of long-term parasitism, there might be a complex interrelationship between Paragonimus and microorganisms. Our study might shed lights on the understanding of the pathogenicity of Paragonimus.

Excretion of dietary zinc in mammals (rats) fed overdoses of zinc lactate and infected with tapeworms

SummaryTapeworms parasitize at sites that are important for the management of micronutrients, including zinc. Therefore, it has been hypothesized that tapeworms will significantly affect the excretion of zinc in the feces of a host. The aim of this work was to evaluate the effects that tapeworms have on the excretion of zinc in the feces of the host. Rats were divided into 4 groups: groups 0T and MT (infected with Hymenolepis diminuta (Rudolphi, 1819)) and groups 00 and M0 (uninfected). The experimental groups (M0 and MT) were fed a standard rodent compound feed (ST-1) with added zinc lactate; the daily zinc intake was 20.5 mg. The control groups (00 and 0T) were fed only ST-1 with 1.75 mg of added Zn per day. For six weeks, the amount of consumed feed was recorded and fecal samples were taken. The samples were then analyzed by optical emission spectrometry (ICP-OES), and levels of excreted zinc were subsequently calculated as a percentage. The most signifi cant difference in zinc excretion levels between the experimental groups was observed in the third week, when rats infected with tapeworms (MT) excreted substantially lower levels of zinc than did uninfected rats (M0). This difference amounted to 28.36 % (p <0.01). In the control groups, tapeworms affected the excretion of zinc in the feces to a lesser extent, and the most substantial difference in zinc levels was seen in the fifth week (8.46 %). However, there was no signifi cant difference in zinc excretion levels between the control groups during any of the monitored weeks. Tapeworms in the host affect levels of zinc excreted in the feces. However, this is dependent on the amount or form of zinc ingested.

1106. Evaluation of Penetration of Cefiderocol into Cerebrospinal Fluid Using a Rat Meningitis Model

BackgroundCentral nervous system (CNS) infections caused by Gram-negative bacteria (GNB) are sometimes hard to treat due to antibiotic resistance and difficulty with penetration into cerebrospinal fluid (CSF). Cefiderocol (CFDC) which was approved by the FDA and the EMA in 2019 to 2020 is a siderophore cephalosporin with potent activity against various GNB including carbapenem-resistant strains. In this study, we evaluated the penetration of CFDC into CSF using a rat meningitis model. MethodsTo induce meningitis, the anesthetized immunocompetent rats were infected by intracisternal inoculation of a bacterial suspension of 8.7×101 CFU of E. coli SR200138. 200 mg/kg or 50 mg/kg of CFDC was administered via tail vein bolus injection to uninfected rats (n=4/sampling point) and rats with meningitis (n=4/sampling point) 24 hours after infection. CSF was collected by cisternal puncture and blood was collected from heart. The samplings were performed 0.25, 0.5, 1, 3, and 5 hours after dosing. The concentrations of CFDC in plasma and CSF for individuals were determined by LC/MS/MS. PK parameters for the average values in plasma and CSF were calculated. ResultsCFDC concentration and the PK parameters are shown in Figure and Table, respectively. The penetration of CFDC from plasma to CSF was observed in both uninfected and meningitis groups, and the penetration rates increased in the rats withs meningitis (AUCCSF/AUCplasma: 0.149-0.183) compared with the uninfected rats (AUCCSF/AUCplasma: 0.0508-0.0588). The penetration rates of CFDC in the meningitis were comparable to those of piperacillin, cefepime, and meropenem in human (0.32, 0.103, and 0.39 in strongly inflamed meninges, respectively) [1]. In both groups, elimination of CFDC from CSF was slower compared with that from plasma as seen with other β-lactam antibiotics such as meropenem, suggesting that T> MIC, an indicator that correlates with the efficacy of β-lactams, may be higher in CSF [2].Table. PK Parameters of Cefiderocol after Intravenous Bolus Administration in Uninfected Rats and Rats with Meningitis Figure. Concentrations of Cefiderocol after Intravenous Bolus Administration in Uninfected Rats and Rats with Meningitis ConclusionIt was confirmed that CFDC penetrates into CSF from plasma in a rat model and the penetration rate was increased 3-fold in meningitis.

Combined effects of heavy metals and parasite infections on the haematological and biochemical profiles of wild rats from Awotan Municipal Dumpsite in Ibadan City

The combined effects of heavy metals and parasitic infections on wild rats from Awotan municipal dumpsite in Ibadan city southwest Nigeria were determined. A total of thirty rats were captured from the dumpsite and five rats from a control site using live traps. Rats were identified, weighed and body length measured to determine body condition index. Blood samples were collected from the rats using the cardiac puncture method. Rats were euthanized and dissected to extract various organs (kidney, liver and intestine). Intestinal helminths were extracted, identified and preserved. Blood parasites were identified using Giemsa staining technique of thick and thin films while intestinal helminths recovered were preserved and identified to species level. Organs, intestinal helminths and blood samples were digested and concentrated for heavy metals (Fe, Cu, Cr, Cd, and Pb) using Atomic Absorption Spectrophotometry (AAS). Cortisol level was determined using ELISA technique. All statistical significance was at probability value p &lt; 0.05. Three species of rats were captured, Rattus rattus, Rattus novergicus and Cricetomys gambianus. The mean ± sd of the body condition index of the rats from dumpsite and control groups were 1.82±0.17 and 1.59± 0.38 respectively. There were significant differences in the mean values of eosinophils, platelets and white blood cell counts of rats from the two study sites. Overall parasite prevalence in dumpsite and control were 76.6% and 20% respectively. The overall prevalence of parasite species from dumpsite was in the order Hymenolepis diminuta (26.6%) &gt;Monoliformis monoliformis (20%) &gt;Plasmodium spp (20%) &gt;Trypanosoma spp (10%). The mean concentration (mg/kg) of heavy metals in kidney, liver, intestine and blood of wild rats from both dumpsite and control decreased in the order Fe&gt; Cr&gt; Cu&gt; Cd&gt; Pb. Cortisol level was higher in infected rats from dumpsite (351±58.83ng/ml) than in uninfected rats from dumpsite (237.22± 44.46ng/ml), indicating exposure to immune stressors. A higher prevalence of parasitic infection, heavy metal pollution and the elevated cortisol concentrations in infected rats showed that the animals’ health and well-being are compromised.

Effects of excessive dietary zinc or zinc/cadmium and tapeworm infection on the biochemical parameters in rats.

The main objective of this study was to determine which biochemical blood parameters can serve as indicators of Zn or Zn/Cd burden and tapeworm infection. This study was performed on 44 Wistar male rats during a 6-week period, when rats were or were not fed a zinc/cadmium rich diet and were or were not infected with tapeworms (Hymenolepis diminuta). Total protein, albumin, urea, glucose, triacylglycerols, non-esterified fatty acids, cholesterol, alkaline phosphatase, aspartate aminotransferase, uric acid, Mg, Ca, P and Zn levels were analysed. Control rats with tapeworm infection had significantly higher (p≤0.05) total protein, urea and phosphorus concentrations than did rats unaffected by any experimental factor. Rats given overdoses of zinc lactate exhibited significantly lower glucose levels than did the other rats, especially those infected with tapeworms. Low glucose level in uninfected rats indicate a Zn overdose; high doses of zinc lactate likely decrease levels of glucose via cortisol, which is released during stress. Rats fed the Zn/Cd hyperaccumulating plant Arabidopsis halleri and infected with tapeworms had significantly higher (p≤0.01) cholesterol and urea levels but lower zinc, triacylglycerol, and alkaline phosphatase levels than did rats fed the same diet but free of tapeworms. The increase of alkaline phosphatase level in uninfected rats may indicate both Zn/Cd burden and rat liver damage. Overall, this study not only supports the theory that H.diminuta can serve as a promising model for helminth therapy of the host mammal but also confirmed that this tapeworm is capable to protect somehow the host organism from the harmful effects of heavy metals.

Comparative study between zinc oxide nanoparticles synthesis by biogenic and wet chemical methods in vivo and in vitro against Staphylococcus aureus

ZnO nanoparticles (ZnO-NPs) can be used as nano medicine for Staphylococcus aureus infection, which causes deleterious effects on liver, kidney and lung tissue, as it causes catarrhal bronchitis, peri-bronchial oedema, lymphocytic granulomas, oedematous fluid and haemorrhage inside the bronchi, and interstitial pneumonia. In this research ZnO nanoparticle (ZnO-NPs) synthesis by biogenic method using green alga Ulva fasciata and by wet chemical method. Both of them tested in vitro and in vivo against Staphylococcus aureus. The characterization of ZnO-NPs was detected by U.V spectroscopy, Fourier-transform infrared (FTIR), Energy dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD), Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM). In vivo assessment eight groups, each group contain of five rats and the treatment as follow (1) an uninfected control group; (2) an infected group; groups (3), (4), and (5) were injected with biogenic or chemical ZnO-NPs or zinc acetate, as the bulk group, respectively; and groups (6), (7) and (8) were infected and then treated in the same manner as groups (3), (4), and (5), respectively. The blood profile, biochemical parameters, phagocytic activity and histological assessment of liver, kidney and lung tissue of each rat was investigated after 20 days. The rats treated with 5 mg/1 kg natural ZnO-NPs showed improved lung characteristics, and the number of platelets in the infected groups treated with ZnO-NPs from chemical and natural sources (G6 and G7) was close to those in the control group. However, the trend was reversed for regarding lymphocytes, which remained at higher levels in uninfected animals treated with synthetic ZnO-NPs (G4) than in infected rats treated with synthetic ZnO-NPs (G7). Moreover, a significant difference in phagocytic activity was found among all groups compared to that of controls. Compared to control group rats (G1), uninfected rats injected with only natural ZnO-NPs (G3) showed a significant (P < 0.05) improvement in the phagocytic index. We propose that ZnO-NPs produced from natural sources are preferable to those produced from chemical sources for use as nano medicine for the treatment of S. aureus infection in albino rats.

Label-free serum detection of Trichinella spiralis using surface-enhanced Raman spectroscopy combined with multivariate analysis

Based on blood serum surface-enhanced Raman spectroscopy (SERS) analysis, this paper proposed a simple and unlabeled non-invasive serum detection for T. spiralis infection. Serum samples were collected and analyzed from 40 rats at 0 days post infection (dpi) (normal rats), 19 uninfected rats, and 16 rats infected with T. spiralis at 28 dpi, using SERS measurements. Multivariate statistical techniques, such as linear discriminant analysis (LDA) and principal components analysis (PCA), were used to analyze and identify the obtained blood serum SERS spectra. The diagnosis algorithms, based on PCA-LDA, achieved a diagnostic sensitivity of 87.5%, a specificity of 94.7%, and an accuracy of 91.4% for separating the samples infected with T. spiralis from the control samples. This exploratory study demonstrated that colloidal Ag NPs-based SERS serum analysis technique combined with PCA-LDA has a great potential in improving the detection of T. spiralis infection and onsite screening.

2592. Lung Function as an Indicator of Vaccine Enhanced RSV Disease in Cotton Rats

BackgroundRespiratory syncytial virus (RSV) infection is the leading cause of lower respiratory tract infections in infants and young children. Seronegative children previously vaccinated with formalin-inactivated live RSV formulated with aluminum (FIRSV) developed vaccine enhanced RSV disease (VERD), which is characterized by fever, wheezing, bronchopneumonia, and airway hyperresponsiveness (AHR). We investigated whether impaired lung function can serve as a marker for VERD in an animal model of RSV infection.MethodsUninfected and RSV-infected cotton rats intranasally challenged with 106 pfu of RSV A2 were anesthetized with pentobarbital and tracheostomized. A cannula was placed in the trachea and animals were connected to flexiVent™ (Scireq), which is a computer-controlled piston ventilator that analyzes pressure and volume signals in response to an oscillatory waveform applied at the animal’s airways. Vecuronium bromide was administered to ventilated animals to prevent independent breathing. To measure AHR, animals were exposed to increasing doses of inhaled methacholine, and methacholine-induced bronchoconstriction was measured.ResultsTwo independent studies showed that RSV-infected cotton rats (n = 4) exhibited increased total respiratory system resistance (Rrs) and airway resistance (Rn) following methacholine challenge on days 4 and 6 post-infection compared with uninfected cotton rats (n = 4).ConclusionRSV-induced impairment in lung function can be exploited for the development of a more robust and objective method for assessing vaccine safety in a cotton rat model of respiratory disease compared with traditional histopathological analysis.Disclosures All authors: No reported disclosures.

Exploring the tissue tropism of pseudorabies virus based on miRNA level analysis

BackgroundPseudorabies virus (PRV, or suid herpesvirus, SuHV-1), a member of the herpesvirus family, has an extremely broad host range and threatens the pig industry in China. PRV can evade host innate immunity and infect the kidney, lung, brain and other tissues. At the same time, many studies have reported that microRNA (miRNA) can affect the replication of viruses by regulating gene expression levels.ResultsHere, to identify changes in miRNA expression and post-transcriptional regulation associated with PRV infection in the lung, spleen, and olfactory bulb, we sequenced small RNAs in tissues of rats infected or uninfected with PRV strain XJ (PRV-XJ). Sixty-one, 199 and 29 differentially-expressed miRNAs were identified in the lung, spleen, and olfactory bulb, respectively, of infected compared with uninfected rats. Among the miRNAs differentially-expressed in PRV-infected rats, 36, 171, and 15 miRNAs showed tissue-selective expression in the olfactory bulb, lung and spleen, respectively. All differentially-expressed miRNAs were analyzed for their GO functional annotations and KEGG pathway associations .ConclusionsIn PRV-XJ-infected rats, miRNAs were differentially expressed in the lung, spleen and olfactory bulb. These miRNAs were involved in regulating various pathways of the nervous, respiratory and immune systems, and may affect the tissue tropism of the virus and play pivotal roles in viral infection and proliferation.

Cytokine modulation, oxidative stress and thymic dysfunctions: Role of age-related changes in the experimental Trypanosoma cruzi infection: Age-related thymic dysfunctions and Trypanosoma cruzi infection

Aging is linked with a thymic oxidative damage and some infectious diseases such as Chagas’ disease may aggravate this process. The aim of this study was to evaluate the production of distinct cytokines as well as the antioxidant/oxidant status of the thymus and thymocytes populations during Trypanosoma cruzi (T. cruzi) infection. Young (5 weeks old) and aged (18 weeks old) male Wistar rats were inoculated with blood trypomastigotes forms of the Y strain of T. cruzi. On the 16th day after T. cruzi infection, increased concentrations of transforming growth factor β (TGF-β), interleukin (IL)-12, IL-17 were detected in aged infected subjects as compared to young infected ones. Interestingly, a reduction in the production of tumor necrose factor (TNF)-α was observed in aged infected rats when compared to young infected subjects. Aged-infected rats presented increased O2− levels, compared to young counterparts. Significant raise in the generation of O2− in aged infected animals, as compared to uninfected counterparts was observed. Up-regulated expression of Nox2 in the thymus of young and aged infected animals was observed. An increased SOD2 expression was detected in the thymus of young animals infected with T. cruzi, when compared to uninfected young rats. Aged animals showed reduced thymus weight and the number of thymocytes. Decreased percentages of SPCD4+ and SPCD8+T cells were detected in aged and control groups when compared to young counterparts. In summary, this is the first data to directly examine the influence of aging on age-related dysfunctions during the acute phase of experimental Chagas disease. Concerning to oxidative stress, it is clear from our analysis that aged infected rats suffer a more intense oxidative damage when compared to young and infected ones. Age and infection triggered a dynamic interplay of cytokines, oxidative stress and thymic dysfunctions which led to impaired response from aged and infected rats. Such findings may have significant functional relevance in therapeutic strategies in order to reestablish the thymic immunological function which occurs in aged and T. cruzi infected subjects.

Active Transport of Peptides Across the Intact Human Tympanic Membrane

We previously identified peptides that are actively transported across the intact tympanic membrane (TM) of rats with infected middle ears. To assess the possibility that this transport would also occur across the human TM, we first developed and validated an assay to evaluate transport in vitro using fragments of the TM. Using this assay, we demonstrated the ability of phage bearing a TM-transiting peptide to cross freshly dissected TM fragments from infected rats or from uninfected rats, guinea pigs and rabbits. We then evaluated transport across fragments of the human TM that were discarded during otologic surgery. Human trans-TM transport was similar to that seen in the animal species. Finally, we found that free peptide, unconnected to phage, was transported across the TM at a rate comparable to that seen for peptide-bearing phage. These studies provide evidence supporting the concept of peptide-mediated drug delivery across the intact TM and into the middle ears of patients.

12. The Effect Of Neem Leaves (Azadirachta Indica) Extract To The Blood Profile Of Male Rat (Rattus Norvegicus) Infected With Trypanosoma Evansi Of Krueng Raya Isolat

This study aimed to determine the ability of neem leaf extract to maintain the normal blood profile of white male rat (Rattus norvegicus) infected with Trypanosoma evansi. A total of 24 male white rats were divided into 6 groups. The K0 group as the negative control received no T. evansi infection and no neem leaf extract. Furthermore, K1 group (positive control) only infected with T. evansi, K2 and K3 were given neem leaf extract 50mg/kg BW and 100mg/kgBW, while K4 and K5 were given neem leaf extract 400mg/KgBW and K5 800mg/kgBW. The neem leaf extract was administered for 3 consecutive days after infection established. The blood of the rats was collected to determine the amount of erythrocyte and leukocyte, hemoglobin level and hematocrit value. The data were analyzed using Analysis of Variance (ANOVA) through SPSS for Windows 16.0. The averages (+SD) of erythrocyte of K0, K1, K2, K3, K4, and K5 were 5,64±0,57; 2,31±1; 1,93±0; 0; 2,55±0,33; and 2,56±0,48. The amount of leukocyte were 4,46±1,09; 4,45±1,91; 5,25±0; 0; 8,42±1,66; and 8,14± 5,17. The value of hemoglobin were 12,00±0,47; 10,50±0,57; 4,30±0; 0; 5,60±0,20; and 9,03±0,66. The level of hematocrit 38,00±1,83; 25,00±9,90; 15±0; 0; 18,00±2,65, and 20,75±1,71. The result showed that the administration of neem leaf extract with doses 400mg/kgBW and 800mg/kgBW were difference significantly (P0.05) compare to the positive control of rats, but could not equalize blood profile of uninfected white male rats

Renovascular hypertension increases serum TNF and CX3CL1 in experimental Trypanosoma cruzi infection.

Trypanosoma cruzi triggers a progressive inflammatory response affecting cardiovascular functions in humans and experimental models. Angiotensin II, a key effector of the renin-angiotensin system, plays roles in mediating hypertension, heart failure, and inflammatory responses. T. cruzi and AngII can induce inflammatory responses by releasing inflammatory mediators. The aim of this study was to evaluate systemic AngII, tumor necrosis factor (TNF), and CX3CL1 mediators in a two-kidney one-clip (2K1C) renovascular hypertension model using Wistar rats infected with T. cruzi. Our data showed an increase in serum AngII in uninfected and T. cruzi-infected rats 1 week after 2K1C surgery compared to non-2K1C (Sham) animals. The baseline systolic blood pressure was higher in both uninfected and infected 2K1C rats. Despite no difference in circulating parasites in the acute phase of infection, elevated serum TNF and CX3CL1 were observed at 8 weeks post-infection in 2K1C rats in association with higher cardiac inflammatory infiltration. In summary, AngII-induced hypertension associated with T. cruzi infection may act synergistically to increase TNF and CX3CL1 in the 2K1C rat model, thereby intensifying cardiac inflammatory infiltration and worsening the underlying inflammation triggered by this protozoan.

Analysis of lead pollution levels within an urban ecosystem using the cestode Hymenolepis diminuta and its rat hosts as bioindicators.

The overall goal of this study was to use the Rattus spp./Hymenolepis diminuta model to assess environmental lead pollution in different landscape units of an urban ecosystem. Rats of the genus Rattus were collected from three shanty towns and three residential neighbourhoods of the city of Buenos Aires. Concentrations of lead in the livers of wild rats and in their parasite H. diminuta were measured using inductively coupled plasma mass spectrometry (ICP-MS). The landscape unit and tissue type had a significant effect on lead concentration, being higher in residential neighbourhoods as well as in H. diminuta tissue. Nevertheless, no significant differences were found for the mean lead concentration in livers between uninfected and infected rats. Since the available information describing heavy-metal pollution within the city of Buenos Aires is scarce, the results of this study allow us to update data about the extent of biologically available lead contamination. Considering that rats and H. diminuta are distributed worldwide, this monitoring system for lead pollution might be applied successfully in other urban ecosystems.

Maternal treatment with short-chain fatty acids modulates the intestinal microbiota and immunity and ameliorates type 1 diabetes in the offspring.

We recently hypothesized that the intestinal microbiota and the innate immune system play key roles in the mechanism of Kilham Rat Virus-induced type 1 diabetes in the LEW1.WR1 rat. We used this animal model to test the hypothesis that maternal therapy with short-chain fatty acids can modulate the intestinal microbiota and reverse virus-induced proinflammatory responses and type 1 diabetes in rat offspring. We observed that administration of short-chain fatty acids to rat breeders via drinking water prior to pregnancy and further treatment of the offspring with short-chain fatty acids after weaning led to disease amelioration. In contrast, rats that were administered short-chain fatty acids beginning at weaning were not protected from type 1 diabetes. Short-chain fatty acid therapy exerted a profound effect on the intestinal microbiome in the offspring reflected by a reduction and an increase in the abundances of Firmicutes and Bacteroidetes taxa, respectively, on day 5 post-infection, and reversed virus-induced alterations in certain bacterial taxa. Principal component analysis and permutation multivariate analysis of variance tests further revealed that short-chain fatty acids induce a distinct intestinal microbiota compared with uninfected animals or rats that receive the virus only. Short-chain fatty acids downregulated Kilham Rat Virus-induced proinflammatory responses in the intestine. Finally, short-chain fatty acids altered the B and T cell compartments in Peyer’s patches. These data demonstrate that short-chain fatty acids can reshape the intestinal microbiota and prevent virus-induced islet autoimmunity and may therefore represent a useful therapeutic strategy for disease prevention.