Infected Rats Research Articles

ИЗМЕНЕНИЯ ПЛАЗМАТИЧЕСКИХ КЛЕТОК КРЫС ПРИ ЭКСПЕРИМЕНТАЛЬНОМ ЗАРАЖЕНИИ ТРИХИНЕЛЛАМИ

For experimentally infected rats with Trichinella spiralis (Owen, 1835) Railliet, 1895, spleen and bone marrow are shown to play an important role in the host immune responses. We have studied a role of plasma cells in formation of protective responses for experimental Trichinella infection of white rats. It's been established that a degree of immunological transformation directly depended on a stage of Trichinella spiralis in the host. A stimulating effect of Trichinella has been shown at early intestinal and early muscular stages of the parasite's development. In these periods, high levels of blast cells with mitoses and high number of plasma cells were noticed. A suppressive effect of Trichinella at migration stage was accompanied by decrease of proliferation level and numbers of plasma cells, leading to suppression of the host immune response. Also, a sinusoid-like flow of plasmacytic reaction and mitotic activity of spleen cells had been noted. During studies of morphological composition of peripheral blood increase in eosinophils' numbers was noted. This fact may be explained by the migration of Trichinella larvae, which may cause defensive reactions in the host (eosinophils are excreted into blood). Key words: Trichinella spiralis, white rats, bone marrow, tear, defense reactions of the organism.

VITAMINS C AND E AS AMELIORATIVE AGENTS ON BODY TEMPERATURE AND SERUM CHEMISTRY OF WISTAR RATS INFECTED WITH T. brucei brucei (Federe strain)

Effect of oral administration of vitamins C and E on the body temperature and serum chemistry of Wistar rats infected with T. brucei brucei (Federe strain) was investigated. Twenty-five Albino Wistar rats were randomly divided into five groups of five animals each. Group I was administered with 0.5 mL normal saline only, group II was inoculated with 0.1 × 106 in 0.2 mL blood/PBS of T. brucei brucei only. Groups III, IV, and V were administered the same dose of parasites as in group II, and in addition, they were administered with 150 mg/kg b.w. of Vitamin C; 150 mg/kg b.w. of Vitamin E, and the combination of both Vitamins in the last group, respectively. Body temperature increased consistently in all groups except group I. However, there was a significant (P< 0.05) difference in all treated groups compared to group II on day 28 post-infection. ALT was significantly (P< 0.05) lower only in the group treated with combined vitamins compared to group II. AST and Creatinine decreased significantly (P< 0.05), whereas the decrease recorded for Urea was highly significant (P< 0.01) in all the treated groups compared to group II, values recorded for ALP followed the same pattern but in a converse direction. In conclusion, the administration of vitamins C and E, particularly in its combined form ameliorated the negative effect on the body temperature and serum biochemistry profiles of the infected rats

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.

Chitosan electrospun nanofibers derived from Periplaneta americana residue for promoting infected wound healing

Periplaneta americana has been used medicinally for years to treat a wide variety of skin lesions or ulcers. However, a sizable portion of the drug residues that are retained after extraction are routinely thrown away, thus posing a hazard to the environment and depleting resources. In this study, low molecular weight Periplaneta americana chitosan (LPCS) and high molecular weight Periplaneta americana chitosan (HPCS) were extracted from Periplaneta americana residue (PAR) based on the conventional acid-base method and two deacetylation methods. Moreover, the physicochemical properties and structural differences between the above two chitosan and commercial chitosan (CS) were compared using different methods. Next, two nanofibers comprising different ratios of Periplaneta americana chitosan (LPCS or HPCS), polyvinyl alcohol (PVA), and polyethylene oxide (PEO) were prepared and optimized. The above nanofibers exhibited excellent mechanical properties, antibacterial properties, and biocompatibility while facilitating wound healing in an infected rat whole-layer wound model by promoting wound closure, epithelialization, collagen deposition, and inflammation reduction. In brief, this study produced an effective and affordable wound dressing and offered a suggestion for the comprehensive utilization of Periplaneta americana residue.

Synergism of Azadirachta indica Seed and Nigella sativa on Plasmodium falciparum: Study on Wistar Rats

Aim: This study was carried out to determine the Phytochemical contents of Azadirachta indica seed and Nigella. sativa and their synergistic therapeutic effect on indices of clinical importance in malaria-induced male wistar rats.
 Study Design: The animals that were used for this study where divided into 4 groups of 6 rats each. All rats in the 3 test groups were inoculated with 0.2 ml blood parasitized with Plasmodium falciparum and observed for 3 days for manifestation of signs of malaria. Treatment with Azadirachta indica seed extract only, Nigella sativa extract only and a combination of Azadirachta indica seed and Nigella sativa extracts was conducted for a period of 14 days. Changes in weight of the rats and hematological parameters RBC, WBC,PCV and Hemoglobin were assessed before commencement of treatment and through the 14 day period.
 Place and Duration of Study: This study was conducted at the National Veterinary Research Institute (NVRI), Vom in collaboration with the Department of Biological Sciences Abubakar Tafawa Balewa University, Bauchi, Nigeria between March 2022 and May 2022. 
 Methodology: Azadirachta indica seed and Nigella sativa seeds were extracted with distilled water and the lethal doses (LD₅₀) were determined on the rats. Qualitative phytochemical screening of Azadirachta indica seed and Nigella sativa extracts was performed. Plasmodium infected rats were divided into 3 groups of 6 rats each and a normal control group which was left uninfected. Symptoms of malaria infection were observed three days after infection. The treatment was commenced on day 4 post-infection and was continued for a period of 14 days. Each plant extract and the mixture of both extracts were administered at 100, 200, and 300mg/kg body weight of the rats. After first 4 days, 7 days, and at 14 days of treatment each rat’s blood sample was taken for hematological analysis.
 Results: The plant extracts lethal dose (LD₅₀) was considered safe for Azadirachta indica seed at 5000mg/kg and 2000mg/kg for Nigella sativa respectively. Qualitative phytochemical screening revealed the presence of saponins, alkaloids, flavonoids, resins, glycosides, steroids in both Azadirachta indica seed extract and Nigella. sativa extract. Treatment with a mixture of both extracts showed a high restoration of red blood cell count with a significant (p>0.05) increase in RBC with a non-significant decrease in PCV and WBC. There was no significant decrease in hemoglobin concentration observed across all treatment groups at the end of the 14 day study.
 Conclusion; The combination of both Azadirachta indica seed and Nigella sativa is well tolerated and safe for Plasmodium parasites effects on wistar rats at concentration of 400mg/kg of body weight which showed highest values of restoration of RBC count as compared to the normal control group. Group A treated with only Nigella sativa also showed RBC count higher than that obtained in group B treated with only Azadirachta indica seed. PCV values compared with the normal control group showed an 8% increase at concentration of 400mg/kg at the end of the experiment in group C treated with the mixture of Azadirachta indica seed and Nigella sativa. At 200mg/kg concentration, the mixture of Azadirachta indica seed and Nigella. sativa gave a 25% increase in PCV values. This shows that the synergistic effect of Azadirachta indica seed and Nigella sativa has better therapeutic effects against Plasmodium parasites than either Nigella sativa or Azadirachta indica seed as a single therapy. This study provides a basis for the development of a cheaper plant-based antimalarial combination therapy.

Histopathological and Biochemical Evaluation of Albendazole in the Treatment of Infected Mice with Hydatid Cyst

Introduction: Hydatidosis, caused by the larval stage of Echinococcus granulosus, is a prevalent parasitic disease affecting both humans and animals. Albendazole is currently the most effective drug for treating hydatid cysts. This research aimed to investigate the histopathological and biochemical effects of Albendazole on the liver, lung, and kidney of mice experimentally infected by hydatid cysts.
 Materials and methods: A total of 20 mice weighing approximately 220 g were used. The rats were randomly divided into the Albendazole group (100 mg/kg/day) and the control group (infected Rats without treatment). At the end of the experiment, tissue samples from the liver, lung, and kidney were collected for histopathological evaluation. Liver blood tests were used to assess liver functions or liver injury (alkaline phosphatase, alanine aminotransferase, and bilirubin).
 Results: After 30 days of daily treatment, the total numbers of cysts, size, and weight of the largest cyst were significantly lower in the Albendazole group, compared to the control group. The study addressed histopathological changes in the liver, kidneys, and lungs caused by hydatid cysts, such as tissue necrosis, hemorrhage, and local inflammation, indicating the potential for serious complications and significant damage to these organs. The group treated with Albendazole showed severe histopathological changes in the liver, kidneys, and lungs, compared to the control group. This suggests that Albendazole may trigger a more aggressive response in these organs to the cysts, leading to increased tissue damage. In addition, alkaline phosphatase, alanine aminotransferase, and bilirubin concentrations revealed a significant increase in the Albendazole group.
 Conclusion: While Albendazole is an effective drug for treating hydatidosis, it can also cause severe side effects on various organs in the body. Therefore, alternative treatment strategies need to be developed to minimize these adverse effects.

Borna disease virus 1 impairs DNA double-strand break repair through the ATR/Chk1 signalling pathway, resulting in learning and memory impairment in rats.

Borna disease virus 1 (BoDV-1) is a highly neurotropic RNA virus that can establish persistent infection in the central nervous system and cause cognitive dysfunction in neonatally infected rats. However, the mechanisms that lead to this cognitive impairment remain unclear. DNA double-strand breaks (DSBs) and their repair are associated with brain development and cognition. If DNA repair in the brain is reduced or delayed and DNA damage accumulates, abnormal cognitive function may result. We generated a rat model of BoDV-1 infection during the neonatal period and assessed behavioural changes using the open field test and Morris water maze. The levels of DSBs were determined by immunofluorescence and comet assays. Western blotting assessed proteins associated with DNA repair pathways. The results showed that BoDV-1 downregulated the ATR/Chk1 signalling pathway in the brain, impairing DNA damage repair and increasing the number of DSBs, which ultimately leads to cognitive dysfunction. Our findings suggest a molecular mechanism by which BoDV-1 interferes with DNA damage repair to cause learning and memory impairment. This provides a theoretical basis for elucidating BoDV-1-induced neurodevelopmental impairment.

Levels of Genetic Variants Among Symptomatic Blastocystis Subtypes and their Relationship to Mucosal Immune Surveillance in the Precancerous Colons of Experimentally Infected Rats

PurposeThe relationship between the genetic diversity of Blastocystis and immune surveillance in precancerous colons with blastocystosis is still under investigation. This study aimed to identify the genetic Blastocystis variants among 54 symptomatic human isolates and their relationship to mucosal immune surveillance in the precancerous polyps of experimentally infected rats.MethodsPolymerase chain reaction and high-resolution melting (PCR/HRM) curves discriminated human symptomatic Blastocystis isolates into subtypes (STs)/intrasubtypes, which were orally administered to rats to induce experimental infection. Then, the mucosal immune responses of the infected colons were evaluated in relation to polyp formation through immunostaining to identify mucus MUC2 and determine mucosal immune cell (goblet, lymphocyte and mast) counts, secretory IgA levels and parasitic intestinal invasion.ResultsST1, ST3, and ST4 were found in 18.5% (10/54), 54.7% (29/54), and 27.8% (15/54) of the samples, respectively. Then, the HRM curve discriminated ST3 into the wild, mutant, and heterozygous [17/54 (31.5%), 5/54 (9.3%), and 7/54 (12.9%)] intrasubtypes. ST1 and ST4 had no genetic variations. Precancerous polyps were detected in the colons of 40.5% of the infected rats. ST1 constituted 14.7% of these cases, while the wild, mutant, and heterozygous intrasubtypes of ST3 showed polyps in 12.9%, 5.5%, and 5.5% of cases, respectively. Only 1.9% of the polyps were related to ST4. MUC2 showed weak immunostaining in 44.5% of the infected colons, and 38.9% were polyp inducers. Low goblet cell numbers and high interepithelial lymphocyte counts were significantly associated with polyp formation, particularly with ST1 and wild ST3. Among the polyp inducers, high numbers of mast cells were detected in wild ST3 and ST4, while a low number was found with heterozygous ST3. The level of secretory IgA was low in polyp-inducing STs. Most of the results were statistically significant.ConclusionImmunosurveillance showed a potential relationship between ST1 and the ST3 intrasubtypes and precancerous polyps. This relationship may provide insight into the prevention and/or development of new immunotherapeutic strategies to combat colorectal cancer.

The impact of L-citrulline on murine intestinal cell integrity, immune response, and arginine metabolism in the face of Giardia lamblia infection

Giardiasis is an intestinal protozoal disease caused by Giardia lamblia (G. lamblia) which is a major worldwide health problem due to development of resistance to commonly used drugs. Therefore, it is necessary to identify an effective drug for giardiasis. This study aimed to assess the therapeutic role of L-citrulline against giardiasis in experimental animals. 40 male Swiss Albino weaned rats were used in this study, divided into four groups. Group I: normal control; group II: infected un-treated; group III: infected and treated with L-citrulline and Group IV: infected and treated with metronidazole. The efficacy was evaluated by counting Giardia trophozoites in the intestinal mucosa and cysts in the stool of infected rats. Histopathological analyses, immunohistochemistry expression of inducible nitric oxide synthase (iNOS) in the small intestine tissues were performed. Along with, serum IL6, the intestinal arginase enzyme level and giardial flavohemoglobin (flavoHb) expression were measured. L-citrulline administration reduced the mean number of G. lamblia cysts and trophozoites, serum IL-6, and intestinal arginase enzyme levels. Furthermore, the intestinal brush border was restored, with a reduction in the inflammatory infiltrate and an increase in iNOS activity. Moreover, there was a significant decrease in flavoHb gene expression in both the L-citrulline and metronidazole treated groups. Thus L-citrulline is effective in NO production therefore it has a therapeutic potential in controlling giardiasis.

Review: Guarding the Golden Gate: A History of the U.S. Quarantine Station in San Francisco Bay, by J. Gordon Frierson

Gordon Frierson’s study examines the history of a quarantine station on Angel Island in San Francisco Bay. Although much larger than better-known Alcatraz Island, it is remarkable how such an isolated location had ties to larger medical, social, and political issues such as California politics, a yellow fever outbreak in New Orleans, anti-Chinese discrimination in the United States, global migration, anti-vaccine movements and two world wars. The author has a gift for narrative and human detail. Overall, this was a beautifully written, jargon-free, and concise work on the important topic of quarantine and public health, as well as the medical history of California.The core of this history is a meticulously researched account of the creation and work of a quarantine station that was designed to protect the West Coast from epidemic diseases. From the start—the arrival of the tramp steamer Altonower in 1882 with smallpox—anti-Asian discrimination determined how people at risk were treated, sometimes with high human costs. When plague arrived in San Francisco in 1900 (p. 64) only Chinatown was quarantined, as authorities literally enclosed it with barbed wire. Neighboring residences were left alone, and quarantine policies were defined by race (p. 67). At the same time, businesses did not want to accept that the threat from plague was real (p. 69), newspapers said that the plague was fake news, and people refused to take the (perhaps ineffective) vaccine (p. 65). Health leaders faced death threats (pp. 68–69), and one took to carrying a revolver. The federal government pushed for strict measures, while the governor fought against taking action. Of course we read the past in the context of our present concerns, so this book reflects many issues related to our current experience of COVID-19, even though our contemporary pandemic is only mentioned in the last two pages.Much of the book details the practical struggles that defined the station’s life. A great deal of this work dealt with fumigation, a truly terrifying topic. One chapter is titled “The Cyanide Era.” Five men (p. 120) died during the fumigation of just one Japanese ship. While extreme measures were taken to prevent plague infected rats from entering the city, class and race always defined public health policy. Parts of the book read as social history, such as when most passengers had to submit to invasive testing, while first-class passengers strolled off the ship with barely a glance from the doctors (p. 78).Frierson’s history of the Angel Island quarantine station (1891–1949) is a thoroughly researched narrative history, which speaks to how public health is shaped by broader social issues, including discrimination and class. Overall, Frierson’s account provides a nuanced but positive depiction of the station’s work, which was ultimately rendered obsolete by medical advances and technological changes. Highly recommended.

Evaluation of wound healing potential of Jatropha curcas leaf extracts ointment based on wound infection in Wistar rats model

This research study was conducted to evaluate the wound healing potential of ointment formulated with Jatropha curcas leaf extracts based on wistrar rat model. The therapeutic activities of the plant extracts were determined by topical application of the herbal ointment. Wound healing rate took place on the 16th day of post treatment with 1.0 g of J. curcas ointment formulation and 12th day with 2.0 g of the ointment, was similar compared with standard drug Gentamicin ointment (12 days). The control untreated group (62.3±0.51%) rate of wound closure observed persisted beyond the 19th day of post-wounding. The haematological parameters of the infected rats treated with herbal ointment and the control group untreated were not significant different (p>0.05). Significant increase in white blood cell (WBC) count in untreated group was recorded when compared with the treated group. However, treatment with the formulated ointments significantly increase the elevated WBC count in the treated group. The toxicological parameters in the serum of the rats are useful makers for the assessment of tissue damage. The serum Aspartate Transaminase (AST) and Alanine Transaminase (ALT) activities in the treated and untreated experimental groups were not significantly (p>0.05) different. The phytochemical components found in J. curcas leaves contain some useful potential antimicrobial agents that possess wound healing properties when formulated into a topical ointment for topical application.

Inverse opal microneedles arrays for fluorescence enhanced screening skin interstitial fluid biomarkers

Infectious diseases caused by bacteria have become serious health concerns. Efficient and sensitive early detections are of pivotal significance in the diagnosis and treatment of bacterial infection. Here, we develop novel inverse opal microneedles (MNs) arrays for in situ extraction and fluorescence-enhanced detection of target biomarkers in skin interstitial fluid (ISF). As the MNs array is fabricated by applying a resin to replicate the colloidal crystal-filled negative mold, it possesses the exceptional arranged porous structure and unique photonic band gap (PBG) properties. Benefitting from these features, the inverse opal MNs array enables non-invasive skin ISF sampling and provides enhanced fluorescence signal intensity towards specific bio-probes, facilitating improved detection sensitivity. On the basis of the inverse opal MNs array, we have further verified its value of in situ extraction and fluorescence-enhanced detection of lipopolysaccharide (LPS) with high efficiency and sensitivity in skin ISF from infected rats. These results indicate the great potential value of the inverse opal MNs array in non-invasive clinical diagnosis and other related biomedical applications.

Efficacy of an Antibiotic Loaded Ceramic-Based Bone Graft Substitute for the Treatment of Infected Non-Unions.

The treatment of non-unions is often complicated by segmental bone defects and bacterial colonization. Because of the limited availability of autologous bone grafts, tissue engineering focuses on antibiotic-loaded bone graft substitutes. HACaS+G is a resorbable calcium sulphate-hydroxyapatite loaded with gentamicin. The osteoinductive, osteoconductive, and anti-infective effect of HACaS+G has already been demonstrated in clinical studies on patients with chronic osteomyelitis. However, especially for the treatment of infected non-unions with segmental bone defects by HACaS+G, reliable clinical testing is difficult and sufficient experimental data are lacking. We used an already established sequential animal model in infected and non-infected rat femora to investigate the osteoinductive, osteoconductive, and anti-infective efficacy of HACaS+G for the treatment of infected non-unions. In biomechanical testing, bone consolidation could not be observed under infected and non-infected conditions. Only a prophylactic effect against infections, but no eradication, could be verified in the microbiological analysis. Using µ-CT scans and histology, osteoinduction was detected in both the infected and non-infected bone, whereas osteoconduction occurred only in the non-infected setting. Our data showed that HACaS+G is osteoinductive, but does not have added benefits in infected non-unions in terms of osteoconduction and mechanical bone stability, especially in those with segmental bone defects.

Effect of platelet-rich fibrin (PRF) membranes on the healing of infected skin wounds.

Tissue engineering focuses on wound healing and tissue regeneration. Platelet-rich fibrin (PRF) is a fibrin matrix containing cytokines, growth factors and cells that are gradually released into the wound over time. This study aimed to evaluate the effect of PRF membranes on wound repair and microbial control in infected wounds. Skin wounds were performed on the dorsum of rats using a 6mm diameter metal punch. The defects were randomly assigned into four groups (n = 12/each) accordingly to the treatment: G1, noninfected wound filled only with clot; G2, noninfected wound with PRF; G3, infected wound (S. aureus) without PRF; G4, infected wound (S. aureus) with PRF. After 7 and 14days, macroscopic and histological analyses of the wounds were performed. Furthermore, the quantification of β-defensin in PRF was measured by ELISA. At 14days, the groups with PRF (G2 and G4) had wound sizes significantly smaller than the original defects (6mm) (p < 0.05) and significantly smaller than those not treated with PRF, in both the infected and noninfected groups (p < 0.05). Furthermore, the groups with infected wounds (G3 and G4) demonstrated a significantly lower inflammation score in the PRF group than in the noninfected groups (p < 0.05). In vitro analysis of β-defensin was performed in all PRF membrane groups, and the median value was 1.444pg/mL. PRF in the wounds of both control and infected rats played an important role in the modulation of tissue healing, most notably in infected sites.

Rift Valley Fever Virus Infects the Posterior Segment of the Eye and Induces Inflammation in a Rat Model of Ocular Disease.

ABSTRACTPeople infected with the mosquito-borne Rift Valley fever virus (RVFV) can suffer from eye-related problems resulting in ongoing vision issues or even permanent blindness. Despite ocular disease being the most frequently reported severe outcome, it is vastly understudied compared to other disease outcomes caused by RVFV. Ocular manifestations of RVFV include blurred vision, uveitis, and retinitis. When an infected individual develops macular or paramacular lesions, there is a 50% chance of permanent vision loss in one or both eyes. The cause of blinding ocular pathology remains unknown in part due to the lack of a tractable animal model. Using 3 relevant exposure routes, both subcutaneous (SC) and aerosol inoculation of Sprague Dawley rats led to RVFV infection of the eye. Surprisingly, direct inoculation of the conjunctiva did not result in successful ocular infection. The posterior segment of the eye, including the optic nerve, choroid, ciliary body, and retina, were all positive for RVFV antigen in SC-infected rats, and live virus was isolated from the eyes. Proinflammatory cytokines and increased leukocyte counts were also found in the eyes of infected rats. Additionally, human ocular cell lines were permissive for Lrp1-dependent RVFV infection. This study experimentally defines viral tropism of RVFV in the posterior segment of the rat eye and characterizes virally-mediated ocular inflammation, providing a foundation for evaluation of vaccines and therapeutics to protect against adverse ocular outcomes.IMPORTANCE Rift Valley fever virus (RVFV) infection leads to eye damage in humans in up to 10% of reported cases. Permanent blindness occurs in 50% of individuals with significant retinal scarring. Despite the prevalence and severity of this outcome, very little is known about the mechanisms of pathogenesis. We addressed this gap by developing a rodent model of ocular disease. Subcutaneous infection of Sprague Dawley rats resulted in infection of the uvea, retina, and optic nerve along with the induction of inflammation within the posterior eye. Infection of human ocular cells induced inflammatory responses and required host entry factors for RVFV infection similar to rodents. This work provides evidence of how RVFV infects the eye, and this information can be applied to help mitigate the devastating outcomes of RVF ocular disease through vaccines or treatments.

Melatonin regulates antioxidant defense and inflammatory response by activating Nrf2-dependent mechanisms and inhibiting NFkappaB expression in middle-aged T. cruzi infected rats.

Oxidative stress with higher levels of leptin and inflammatory response are key processes related to pathogenesis of both T. cruzi infection and aging. Nuclear factor erythroid 2-related factor 2 (Nrf2) controls the expression of several genes implicated in the oxidative stress response in many pathological conditions. Melatonin is a pleiotropic hormone with, antioxidant, anti-inflammatory and anti-aging actions. Then, we hypothesized that Nrf2 response is impaired during the acute T. cruzi (9days) infection and that melatonin rescues Nrf2 responses. Young (5weeks-old) and middle-aged (18months-old) male Wistar rats were infected with T. cruzi. Nrf2 translocation and markers of inflammation and oxidative stress were analyzed in blood and spleen. Increased apoptosis levels and oxidative stress indicators were observed in the rat spleen during T. cruzi infection. These responses were accompanied by decreased Nrf2 expression and increased expression of nuclear factor kappa B (NFκB). Melatonin (5mg/kg/day; p.o. gavage) attenuated the superoxide anion (O2-) and hydrogen peroxide (H2O2) production induced by T. cruzi infection. Increased expressions of catalase and superoxide dismutase (SOD) were detected in the spleen of melatonin-treated rats infected with T. cruzi. Melatonin treatment inhibited the spleen NF-κB activation and downregulates the levels of circulating interleukin (IL)-4, IL-10 and tumor necrosis factor (TNF)-α in T. cruzi middle-aged infected rats. Increased levels of the chemokine CXCL1 in middle-aged control rats was observed, confirming that aging alters the production of this chemokine. In T. cruzi infected young animals, CXCL1 was up-regulated when compared to non-infected young ones. For young or middle-aged animals, melatonin treatment had no significant effect on CXCL1 levels. Our findings demonstrate an important role for Nrf2/NF-kB regulation as a possible mechanism by which melatonin attenuates oxidative stress, and provide new insights for further studies of this indoleamine as a therapeutic co-adjuvant agent against T. cruzi infection.

Favorable Aspects of Silymarin in Linezolid Treatment Against Diabetic Methicillin-Resistant Staphylococcus aureus (MRSA) Infected Rats

Background: Linezolid used for diabetic methicillin-resistant Staphylococcus aureus (MRSA) infections is limited due to hepatotoxicity, lactic acidosis, anemia, and oxidative stress induced by diabetes and linezolid therapy. Silymarin is a hepatoprotective, antioxidant, antibacterial, and antidiabetic. Objective: The research investigated the role of silymarin in linezolid treatment against MRSA-infected diabetic rats. Methods: Type 2 diabetes mellitus (T2DM) was induced by a high-fat diet (58% calories fat) for 2 weeks, followed by a single intraperitoneal injection of streptozotocin (STZ) 35 mg/kg into Wistar rats. The diabetic rats were rendered neutropenic and subcutaneously injected with 106 CFU/ml of MRSA. Linezolid and silymarin were administered orally at a dose of 50 mg/kg twice daily for 14 days. The bacterial load/abscess, hematological, biochemical, enzymatic parameters, antioxidants, and histopathological studies were performed on the 42nd day. Results: The MRSA was confirmed by PCR assay. The minimum inhibitory concentration of linezolid was found to be 0.5-2 μg/ml. The linezolid treated MRSA infected diabetic rats showed 9.69 x 103 CFU / abscess bacterial count, decreased intestinal alkaline phosphatase (IAP), RBC, antioxidants, elevated lactate, and liver markers than diabetic rats. The silymarin treatment showed a decrease in the bacterial count (2.98 x 103 CFU / abscess), serum lactate, liver markers, increased IAP levels, and antioxidants in linezolid treated diabetic infected rats. Conclusion: The research concluded that silymarin could be a better herbal therapeutic agent that attenuated diabetic and linezolid induced complications in MRSA-infected diabetic rats.

Evaluation of the Lipid Profile of Plasmodium berghei Infected Rats Treated with Aqueous Bark Extract of Cassia spectabilis

The aim of this work was to evaluate the lipid profile of Plasmodium berghei infected rats treated with aqueous extract of Cassia spectabilis. Twenty five (25) adult male wistar rats were divided into five (5) groups of five (5) rats per group. Group I was the normal control fed only rat chow and water, Group II was infected with the parasite without treatment. Groups III and IV were infected with Plasmodium berghei and afterwards treated with 200 mg/kg and 400 mg/kg of aqueous extract of Cassia spectabilis respectively, while Group V was infected and treated with a standard drug (chloroquine). Treatment lasted for 7 days after which animals were sacrificed and blood sample collected. Evaluation of lipid profile was performed by standard procedures. Plasmodium berghei infection significantly (P&lt;0.05) increased Total Cholesterol (TC), Triacylglyceride (TG) and Low Density Lipoprotein (LDL) but significantly (P&lt;0.05) decreased High Density Lipoprotein (HDL) an observation which was reversed following treatment with the aqueous extract of Cassia spectabilis in a dose dependent manner. In conclusion, extract of the said plant wields the potential to recover a stable lipid profile in Plasmodium berghei infected rats.

Nano-Calcium Carbonate Affect the Respiratory and Function Through Inducing Oxidative Stress: A Cross-sectional Study Among Occupational Exposure of Workers and a Further Research for Underlying Mechanisms.

The aim of the study is to investigate whether nano-calcium carbonate (nano-CaCO 3 ) occupational exposure could induce adverse health effects in workers. A cross-sectional study was conducted in a nano-CaCO 3 manufacturing plant in China. Then, we have studied the dynamic distribution of nano-CaCO 3 in nude mice and examined the oxidative damage biomarkers of subchronic administrated nano-CaCO 3 on Sprague-Dawley rats. The forced vital capacity (%) and the ratio of FEV1 to FVC is the rate of one second of workers were significantly decreased than unexposed individuals. Dynamic imaging in mice of fluorescence labeled nano-CaCO 3 showed relatively high uptake and slow washout in lung. Similar to population data, the decline in serum glutathione level and elevation in serum MDA were observed in nano-CaCO 3 -infected Sprague-Dawley rats. We found that nano-CaCO 3 exposure may result in the poor pulmonary function in workers and lead to the changes of oxidative stress indexes.

Puerarin@Chitosan composite for infected bone repair through mimicking the bio-functions of antimicrobial peptides.

It is important to eliminate lipopolysaccharide (LPS) along with killing bacteria in periprosthetic joint infection (PJI) therapy for promoting bone repair due to its effect to regulate macrophages response. Although natural antimicrobial peptides (AMPs) offer a good solution, the unknown toxicity, high cost and exogenetic immune response hamper their applications in clinic. In this work, we fabricated a nanowire-like composite material, named P@C, by combining chitosan and puerarin via solid-phase reaction, which can finely mimic the bio-functions of AMPs. Chitosan, serving as the bacteria membrane puncture agent, and puerarin, serving as the LPS target agent, synergistically destroy the bacterial membrane structure and inhibit its recovery, thus endowing P@C with good antibacterial property. In addition, P@C possesses good osteoimmunomodulation due to its ability of LPS elimination and macrophage differentiation modulation. The in vivo results show that P@C can inhibit the LPS induced bone destruction in the Escherichia coli infected rat. P@C exhibits superior bone regeneration in Escherichia coli infected rat due to the comprehensive functions of its superior antibacterial property, and its ability of LPS elimination and immunomodulation. P@C can well mimic the functions of AMPs, which provides a novel and effective method for treating the PJI in clinic.