Treatment Of Infected Animals Research Articles

In Vivo Evaluation of Leishmanicidal Activity of Benzophenone Derivatives by qPCR

In many tropical areas, infections by Leishmania species are endemic and include visceral leishmaniasis (VL), which is often fatal if untreated. Outside India, VL treatment and control are based on long-term administration of highly toxic pentavalent antimonials. Previously, we described the synthesis and in vitro leishmanicidal activity of a series of nine benzophenone derivatives with low toxicity towards murine macrophages. Here in, we report the in vivo evaluation of the most promising active compounds of that series in an experimental model of established VL by L. (L). infantum chagasi in hamsters. Importantly, parasite DNA (amastigote form) quantification in infected tissues was performed by real time PCR, for improved detection accuracy and speed. Compounds 2-Hydroxy-4- O-(3,3-dimethyl)-allylbenzophenone (LFQM-117 (1)), 4-O-(3,3-Dimethyl)-allylbenzophenone (LFQM-120 (2)) and 4,4′-Di-methoxybenzophenone (LFQM-121 (3)) were administered as oral suspensions (50 mg/kg/day) for 10 days, after 50 days of parasite inoculation, and their efficacy was compared to pentavalent antimonial Glucantime (GLU). Compound 1 significantly reduced the number of parasites in the spleen (1.64 × 102 amastigotes/g, vs. 1.16 × 106 amastigotes/g in the untreated control), while compound 2 significantly reduced (p<0.05) the number of parasites in the liver (1.28 × 104 amastigotes/g, vs. 1.76 × 105 amastigotes/g in the untreated control) of infected animals. Glucantime was the most effective in the treatment of infected animals (1.15 × 101 and 3.20 × 102 amastigotes/g in the spleen and liver, respectively), but with higher toxicity then the most active compounds LFQM-117 (1) and LFQM-120 (2).

Trypanocidal activity of the compounds present in Aniba canelilla oil against Trypanosoma evansi and its effects on viability of lymphocytes.

Aniba canelilla (H.B.K.) Mez, popularly known as "casca-preciosa" (precious bark), is a plant of the Lauraceae family, widely distributed in the Amazon region. Its major constituent is 1-nitro-2-phenylethane, a rare molecule in plants which is responsible for this plant's cinnamon scent. The present study aimed to report the chemical characterization of the oil extracted from Aniba canelilla using gas-chromatography/mass spectrometry and to assess its invitro trypanocidal activity against Trypanosoma evansi, a prevalent haemoflagellate parasite that affects a broad range of mammal species in Africa, Asia and South America. The oil presented 1-nitro-2-phenylethane (83.68%) and methyleugenol (14.83%) as the two major components. The essential oil as well as both major compounds were shown to exert trypanocidal effect. Methyleugenol was slightly more active than 1-nitro-2-phenylethane. Invitro studies showed that the oil extracted from the stems of A.canelilla may be regarded as a potential natural treatment for trypanosomosis, once proven their invivo action, may be an interesting alternative in the treatment of infected animals with T.evansi.

Detection and management of latent infection ofTrypanosoma evansiin a cattle herd

A study was conducted to evaluate the sensitivity of PCR based method for detection of T. evansi and to know its efficacy of corresponding trypanocidal treatment. A total of 101 random blood samples collected from the dairy farm were examined for the presence of Trypanosoma evansi infection. Polymerase Chain Reaction (PCR), using 21/22 mer primers, targeting repetitive sequence probe pMuTec 6.248 to yield 227 bp products was employed. The PCR detected 46.5% animals positive for T. evansi infection in comparison to only 6.9% detected by microscopy using Giemsa stained blood smears. Treatment of infected animals with Triquin (quinapyramine sulphate and chloride) showed improvement in general body condition within a period of two weeks. Results of PCR were also negative for T. evansi in all the post treatment blood samples. Subsequently all the 1400 animals at farm were treated with Triquin. After a period of one month, significant increase in levels of RBC, Hb and HCT and return of the values of BUN and TBIL of treated animals towards normal endorsed the effectiveness of the treatment.

Co-administration of aqueous ginseng extract with tobramycin stimulates the pro-inflammatory response and promotes the killing of Pseudomonas aeruginosa in the lungs of infected rats

North American ginseng is known to have immunomodulatory and antipseudomonal properties in vitro. In this study we investigated the effects of aqueous ginseng extract, either alone or in a combination with the antibiotic tobramycin, in an animal model of chronic Pseudomonas aeruginosa lung infection. The lungs of male rats (n = 5) were infected with P. aeruginosa (2 × 10(8) cfu/mL) in agar-beads by intratracheal instillation. Starting on day 7 post-infection, animals were treated daily for 3 consecutive days with saline, tobramycin (300 μg/kg body mass, intratracheal), and (or) ginseng (100 mg/kg body mass, subcutaneous); animals were sacrificed 24 h after the third drug treatment. Lung bacteria counts, cytokine levels in sera, and lung histopathology were examined. The treatment of infected animals with tobramycin [6.6 × 10(4) colony forming units (cfu)], ginseng (5.3 × 10(4) cfu), or tobramycin plus ginseng (2.0 × 10(3) cfu) lessened the lung infection compared with the control group (saline treated) (6.0 × 10(6) cfu). The levels of pro-inflammatory cytokines (IL-2, IL-4, IL-6, IL-12p70, IFN-γ, GM-CSF, TNF-α) in infected animals were significantly increased with co-treatment of ginseng plus tobramycin. These data suggest that co-administration of aqueous ginseng extract and tobramycin stimulated the pro-inflammatory response and promoted the killing of P. aeruginosa.

A New Murine Model for Gastrointestinal Anthrax Infection.

The scientific community has been restricted by the lack of a practical and informative animal model of gastrointestinal infection with vegetative Bacillus anthracis. We herein report the development of a murine model of gastrointestinal anthrax infection by gavage of vegetative Sterne strain of Bacillus anthracis into the complement-deficient A/J mouse strain. Mice infected in this manner developed lethal infections in a dose-dependent manner and died 30 h-5 d following gavage. Histological findings were consistent with penetration and growth of the bacilli within the intestinal villi, with subsequent dissemination into major organs including the spleen, liver, kidney and lung. Blood cultures confirmed anthrax bacteremia in all moribund animals, with approximately 1/3 showing co-infection with commensal enteric organisms. However, no evidence of immune activation was observed during infection. Time-course experiments revealed early compromise of the intestinal epithelium, characterized by villus blunting and ulceration in the ileum and jejunum. A decrease in body temperature was most predictive of near-term lethality. Antibiotic treatment of infected animals 24 h following high-dose bacterial gavage protected all animals, demonstrating the utility of this animal model in evaluating potential therapeutics.

Mast cell mediated immune pathology during dengue virus infection (P4245)

Abstract Mast cells (MCs) promote immunosurveillance for pathogens in peripheral tissues and line the host vasculature. We observe that MC are activated by dengue virus (DENV), a flavivirus that is spread by mosquito vectors. MC activation by DENV during viremia elevates systemic levels of their vasoactive products, including the MC-specific protease, chymase, and promotes vascular leakage. Symptoms of DENV infection in humans include widespread vascular leakage, pooling of fluid within internal organs and, occasionally, severe hemorrhaging; however, the processes that underlie the immune-mediated vascular pathology during dengue infection are largely unknown. A component of dengue-induced vascular leakage is MC-dependent since mice that lack MCs have greatly reduced vascular permeability during infection. We show that treatment of infected animals with MC-stabilizing drugs restores vascular integrity during experimental DENV infection. Validation of these findings using human clinical samples revealed a direct correlation between MC activation and DENV disease severity based on the measurement of chymase as a serum biomarker. Our findings reveal that MCs mediate DENV-induced vascular pathology, and suggest MC-stabilizing drugs should be evaluated for their effectiveness in improving disease outcomes during viral hemorrhagic fevers.

Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage

Dengue Virus (DENV), a flavivirus spread by mosquito vectors, can cause vascular leakage and hemorrhaging. However, the processes that underlie increased vascular permeability and pathological plasma leakage during viral hemorrhagic fevers are largely unknown. Mast cells (MCs) are activated in vivo during DENV infection, and we show that this elevates systemic levels of their vasoactive products, including chymase, and promotes vascular leakage. Treatment of infected animals with MC-stabilizing drugs or a leukotriene receptor antagonist restores vascular integrity during experimental DENV infection. Validation of these findings using human clinical samples revealed a direct correlation between MC activation and DENV disease severity. In humans, the MC-specific product, chymase, is a predictive biomarker distinguishing dengue fever (DF) and dengue hemorrhagic fever (DHF). Additionally, our findings reveal MCs as potential therapeutic targets to prevent DENV-induced vasculopathy, suggesting MC-stabilizing drugs should be evaluated for their effectiveness in improving disease outcomes during viral hemorrhagic fevers. DOI:http://dx.doi.org/10.7554/eLife.00481.001.

Glucocorticoid treatment of MCMV infected newborn mice attenuates CNS inflammation and limits deficits in cerebellar development.

Infection of the developing fetus with human cytomegalovirus (HCMV) is a major cause of central nervous system disease in infants and children; however, mechanism(s) of disease associated with this intrauterine infection remain poorly understood. Utilizing a mouse model of HCMV infection of the developing CNS, we have shown that peripheral inoculation of newborn mice with murine CMV (MCMV) results in CNS infection and developmental abnormalities that recapitulate key features of the human infection. In this model, animals exhibit decreased granule neuron precursor cell (GNPC) proliferation and altered morphogenesis of the cerebellar cortex. Deficits in cerebellar cortical development are symmetric and global even though infection of the CNS results in a non-necrotizing encephalitis characterized by widely scattered foci of virus-infected cells with mononuclear cell infiltrates. These findings suggested that inflammation induced by MCMV infection could underlie deficits in CNS development. We investigated the contribution of host inflammatory responses to abnormal cerebellar development by modulating inflammatory responses in infected mice with glucocorticoids. Treatment of infected animals with glucocorticoids decreased activation of CNS mononuclear cells and expression of inflammatory cytokines (TNF-α, IFN-β and IFNγ) in the CNS while minimally impacting CNS virus replication. Glucocorticoid treatment also limited morphogenic abnormalities and normalized the expression of developmentally regulated genes within the cerebellum. Importantly, GNPC proliferation deficits were normalized in MCMV infected mice following glucocorticoid treatment. Our findings argue that host inflammatory responses to MCMV infection contribute to deficits in CNS development in MCMV infected mice and suggest that similar mechanisms of disease could be responsible for the abnormal CNS development in human infants infected in-utero with HCMV.

Latent class analysis of the diagnostic characteristics of PCR and conventional bacteriological culture in diagnosing intramammary infections caused by Staphylococcus aureus in dairy cows at dry off

BackgroundStaphylococcus aureus is one of the most common causes of intramammary infections in dairy cows at dry off. Reliable identification is important for disease management on herd level and for antimicrobial treatment of infected animals. Our objective was to evaluate the test characteristics of PathoProof ™ Mastitis PCR Assay and bacteriological culture (BC) in diagnosing bovine intramammary infections caused by S. aureus at dry off at different PCR cycle threshold (Ct)-value cut-offs.MethodsSterile quarter samples and non-sterile composite samples from 140 animals in seven herds were collected in connection with the dairy herd improvement (DHI) milk recording. All quarter samples were analyzed using BC whereas all composite samples were analyzed with PathoProof ™ Mastitis PCR Assay. Latent class analysis was used to estimate test properties for PCR and BC in the absence of a perfect reference test. The population was divided into two geographically divided subpopulations and the Hui-Walter 2-test 2-populations model applied to estimate Se, Sp for the two tests, and prevalence for the two subpopulations.ResultsThe Se for PCR increased with increasing Ct-value cut-off, accompanied by a small decrease in Sp. For BC the Se decreased and Sp increased with increasing Ct-value cut-off. Most optimal test estimates for the real-time PCR assay were at a Ct-value cut-off of 37; 0.93 [95% posterior probability interval (PPI) 0.60-0.99] for Se and 0.95 [95% PPI 0.95-0.99] for Sp. At the same Ct-value cut-off, Se and Sp for BC were 0.83 [95% PPI 0.66-0.99] and 0.97 [95% PPI 0.91-0.99] respectively. Depending on the chosen PCR Ct-value cut-off, the prevalence in the subpopulations varied; the prevalence increased with increasing PCR Ct-value cut-offs.ConclusionNeither BC nor real-time PCR is a perfect test in detecting IMI in dairy cows at dry off. The changes in sensitivity and prevalence at different Ct-value cut-offs for both PCR and BC may indicate a change in the underlying disease definition. At low PCR Ct-value cut-offs the underlying disease definition may be a truly/heavily infected cow, whereas at higher PCR Ct-value cut-offs the disease definition may be a S. aureus positive cow.

ABC transporters of the liver fluke Fasciola hepatica

Background The liver fluke Fasciola hepatica is one of the most important parasites affecting animal health all over the world, causing the so called liver fluke disease (fascioliasis). Infections of mammals can only occur via larvae of the fluke, which live on plants in moistly grassland. Therefore infections of humans are rather rare, but infections of animal stock still lead to large financial losses. The drugs of choice used in the treatment of infected animals are benzimidazoles like triclabendazole, which prevent microtubule formation. During the last decades more and more flukes resistant to these drugs have been found. Beside mutations in the target proteins (b-tubulin), detoxificationmechanisms via ABC (ATP-binding cassette) transporters are thought to be responsible for these resistances. Up to date little is known about proteins of the fluke. We therefore try to isolate yet unknown proteins, focusing mainly on ABC transporters, of the fluke, to investigate their potency as putative new drug targets.

Regulation of inducible heme oxygenase and cyclooxygenase isozymes in a mouse model of spotted fever group rickettsiosis

Vascular endothelial cells (ECs) lining the blood vessels are the preferred primary targets of pathogenic Rickettsia species in the host. In response to oxidative stress triggered by infection, ECs launch defense mechanisms such as expression of heme oxygenase-1 (HO-1). Previous evidence from an established animal model of Rocky Mountain spotted fever also suggests selective modulation of anti-oxidant enzyme activities in the target host tissues. In this study, we have examined the expression profiles of HO-1 and COX-2 in different tissues during Rickettsia conorii infection of susceptible C3H/HeN mice. RNA hybridization with murine HO-1 and COX-2-specific complementary DNA probes revealed increased HO-1 expression in the liver and brain of mice infected with three different doses of R. conorii ranging from 2.25×103 to 2.25×105pfu, relatively non-remarkable changes in the lungs, and a trend for down-regulation in the spleen. The most prominent HO-1 response was evident in the liver with ∼4-fold increase on day 4 post-infection, followed by a decline on day 7. HO-1 expression in the brain, however, peaked with significantly higher levels on day 7. Following infection with both sub-lethal as well as lethal doses of infection, the transcript encoding COX-2 also displayed a pattern of increased expression in the liver and brain. Although immunohistochemical staining revealed increased abundance of HO-1 protein in the liver of infected mice, adjoining serial sections did not exhibit positive staining for COX-2 in infected tissues. The levels of monocyte chemoattractant protein-1 (MCP-1) and keratinocyte-derived cytokine (KC) were significantly higher in the sera of infected mice and corresponded with the onset and severity of the disease. Treatment of infected animals with anti-oxidants α-lipoic acid and N-acetylcysteine and HO inhibitor stannous protoporphyrin (SnPPIX) showed only selective beneficial effects on HO-1 and COX-2 expression in the liver and spleen and serum levels of KC and MCP-1. R. conorii infection of susceptible mice, therefore, results in selective regulation of the expression of HO-1 and COX-2 in a manner dependent on the target host tissue’s cellular environment and the propensity of infection with rickettsiae.

Detection of Listeria monocytogenes by the polymerase chain reaction (PCR) technique in samples of raw bovine milk

Considering the possible incidence of Listeria monocytogenes in raw foods and their pathogenicity and health risk, this study aimed to compare techniques for extraction of bacterial DNA from milk samples and investigate the presence of L. monocytogenes by Polymerase Chain Reaction (PCR) in raw milk. We tested four different extraction protocols (generally identified: A, B, C, and D) for isolation of bacterial DNA directly from milk. In all of them was obtained identifying the product of 702 bp (base pairs) corresponding to the listeriolysin gene from L. monocytogenes . The protocol B containing proteinase K and phenol buffered, was chosen for the extraction of DNA from milk samples from eight dairy farms within the RS. The subsequent PCR amplification with DNA obtained by the protocol B allowed the identification of L. monocytogenes from 10 3 CFU/mL. None of the samples was positive for the producer L. monocytogenes by PCR or by conventional microbiological analysis. With this study it is concluded that the tested protocols, the protocol B was more effective for the detection of L. monocytogenes by PCR. Moreover, for the samples of the producers, the result PCR technique was obtained in a shorter time than conventional analysis of L. monocytogenes , which may allow earlier treatment of infected animals and thus avoid losses to the producer.

Blood electrolytes changes in peritonitis of cattle

Peritonitis is an inflammation of the peritoneal cavity and is one of the main causes of animal deaths. It has been reported that many diseases such as peritonitis cause electrolyte imbalance in the body. The present study has been conducted to evaluate the serum electrolyte concentration in cattle with peritonitis. In order to perform this study, 45 cattle with peritonitis were selected in the Karaj area, and 20 healthy cattle were used as the control group. After diagnosis of peritonitis in the infected cattle, 10-ml blood samples were taken from the jugular vein, the concentrations of calcium, phosphorus, magnesium, and chloride were estimated using the spectrophotometric method, and sodium and potassium concentrations were assessed by a flame photometer device. The results showed that the concentrations of calcium, magnesium, sodium, potassium, and chloride in cattle affected with peritonitis were reduced compared with the control group, but the differences were not statistically significant. The concentration of phosphorus in the peritonitis-infected cattle was significantly higher than in the healthy cattle. On the basis of the results of the present study, it can be concluded that inflammation of the peritoneal cavity in cattle causes blood electrolyte deterioration, and more attention needs to be focused on this factor in the treatment of infected animals.

Evolution of dyskinetoplastic trypanosomes: how, and how often?

Evolution of dyskinetoplastic trypanosomes: how, and how often?

The role of intraperitoneally administered vitamin C during Trypanosoma congolense infection of rabbits.

The effects of daily intraperitoneally administered doses of 100 mg/kg bd. wt. vitamin C on levels of some endogenous antioxidants as well as hepatic and renal function were investigated in a group of rabbits infected with a strain of Trypanosoma congolense (strain number: BS2/TC/SP28/P4). Values of parameters estimated in this group during and after 5 weeks of infection were compared with those from a group of similarly infected, but vitamin-free rabbits as well as two groups of healthy rabbits, one group of which was similarly treated with vitamin C. T. congolense infection caused significant (P<0.01) decrease in packed cell volume (PCV), blood and organ glutathione, plasma and liver ascorbic acid as well as serum creatinine. Treatment of infected animals with vitamin C kept the parasitaemia significantly (P<0.01) lower than in the vitamin-free infected animals after the 3rd week of infection. The vitamin treatment also prevented, to a significant (P< 0.01) degree (and in some cases completely), the disease-induced decreases in blood and organ glutathione (GSH) as well as plasma ascorbic acid. The trypanosomal anaemia was partially, but significantly (P<0.01) ameliorated by vitamin treatment. Infection without vitamin therapy also caused significant (P<0.01) increase in the levels of serum total bilirubin and proteins as well as aspartate and alanine aminotransferases. Vitamin C completely, or to a significant (P<0.01) degree, prevented the disease-induced increases in all these parameters. It was concluded that vitamin C at the dose and route used prevented the disease-induced depletion of endogenous antioxidants, hepatic dysfunction and to a significant degree, anemia.

Senna occidentalis leaf extract possesses antitrypanosomal activity and ameliorates the trypanosome-induced anemia and organ damage

The in vitro and in vivo antitrypanosomal effects of the ethanol extract of Senna occidentalis leaf were investigated. The crude extract exhibited an in vitro activity against Trypanosoma brucei brucei as it completely eliminated parasites’ motility within 10 minutes postincubation with 6.66 mg/ml of effective extract concentration. The extract was further used to treat experimentally T. brucei brucei infected rats at concentrations of 100 and 200 mg/kg body weight, beginning on day 5 post infections (p.i.). At the termination of the experiment on Day 11 p.i., the extract significantly (P < 0.05) kept the parasitemia lower than was recorded in the infected untreated rats. All the infected animals developed anemia, the severity of which was significantly (P < 0.05) ameliorated by the extract treatment. The infection caused significant (P < 0.05) increases in serum alanine and aspartate aminotransferases as well as serum urea and creatinine levels. However, treatment of infected animals with the extract significantly (P < 0.05) prevented the trypanosome-induced increase in these biochemical indices. Furthermore, the T. brucei infection caused hepatomegaly and splenomegaly that were significantly (P < 0.05) ameliorated by the extract administration. It was concluded that orally administered ethanol extract of S. occidentalis leaf possessed anti-T. brucei brucei activity and could ameliorate the disease-induced anemia and organ damage.

Systemic Dendritic Cell Mobilization Associated with Administration of FLT3 Ligand to SIV- and SHIV-Infected Macaques

Reports indicate that myeloid and plasmacytoid dendritic cells (mDCs and pDCs), which are key effector cells in host innate immune responses, can be infected with HIV-1 and are reduced in number and function during the chronic phase of HIV disease. Furthermore, it was recently demonstrated that a sustained loss of mDCs and pDCs occurs in SIV-infected macaques. Since loss of functional DC populations might impair innate immune responses to opportunistic microorganisms and neoplastic cells, we explored whether inoculation of naive and SIV- or SHIV-infected pigtailed macaques with the hematopoietic cytokine FLT3-ligand (FLT3-L) would expand the number of mDCs and pDCs in vivo. After the macaques received supraphysiologic doses of FLT3-L, mDCs, pDCs, and monocytes increased up to 45-fold in blood, lymph nodes, and bone marrow (BM), with DC expansion in the BM preceding mobilization in blood and lymphoid tissues. FLT3-L also increased serum levels of IL-12, at least transiently, and elicited higher surface expression of HLA-DR and the activation markers CD25 and CD69 on NK and T cells. During and after treatment of infected animals, APCs increased in number and were activated; however, CD4(+) T cell numbers, virion RNA, and anti-SIV/SHIV antibody titers remained relatively stable, suggesting that FLT3-L might be a safe modality to expand DC populations and provide therapeutic benefit during chronic lentivirus infections.

Parasitological and clinical responses of lambs experimentally infected with Haemonchus contortus (L 3) with and without ivermectin treatment

Haemonchus contortus is one of the most important parasites that infects sheep and exerts its pathogenic effects by sucking blood, causing disturbances of organ-functions and thus inducing alterations in various normal physiological parameters. Changes in live body weight, faecal egg count, kinetics of circulating eosinophils and PCV value were studied at weekly interval for a period of 84 days in 18 lambs of local breed after infection with a single dose of 5000 H. contortus (L 3). In the two groups of lambs infected with nematodes both non-treated and treated with ivermectin (HcNT and HcIT), similar egg excretion patterns was observed starting from third week after infection, with a regular increase in FEC. Examination of whole abomasum of each animal revealed no developmental stage of nematode from treated and control lambs on day 84. The total mean number of H. contortus worms recovered at necropsy from abomasa of untreated infected lambs (group HcNT) was 2576.2 (±221.0). The significant loss of body weight, development of heavy worm burden and severe anaemia as indicated by reduced PCV in untreated infected lambs indicated high susceptibility of the lambs to H. contortus. On the other hand, complete absence of the parasite, improved PCV value and body weight after treatment of infected animals (HcIT) proved 100% efficacy of ivermectin against H. contortus.

Effect of interleukin-15 on the course of myocarditis in Coxsackievirus B3-infected BALB/c mice

Cytokines have an important role in both the initiation and perpetuation of viral myocarditis. Because a causative therapy of myocarditis is not yet well established and immunomodulation is a promising approach, the influence of interleukin (IL)-15, a proinflammatory cytokine, on the course of experimental myocarditis in Coxsackievirus B3 (CVB3)-infected mice was examined. Hearts from CVB3-infected (n=14), sham-infected (n=14) and CVB3-infected BALB/c mice treated with IL-15 (n=6) or a competitive IL-15 fusion protein (n=6) were analyzed for hemodynamic function, cellular infiltrates and myocardial collagen content. Induction of myocarditis was associated with significant loss of body and heart weight, decreased left ventricular function, and increased collagen content and cellular infiltrates in the myocardium. Treatment of infected animals with IL-15 resulted in normalization of body and heart weight, and significantly improved systolic and diastolic left ventricular function, comparable with that of uninfected animals. This was paralleled by a significant reduction of myocardial collagen content to levels observed in animals without disease and by markedly reduced cellular infiltration of lymphocytes and macrophages in the myocardium. Inhibition of intrinsic IL-15 with IL-15 fusion protein tended to aggravate the disease. Treatment with IL-15 has a positive effect on CVB3- induced murine myocarditis and seems to be a promising approach to modifying clinical course, hemodynamics and histopathology of virus-induced myocarditis. Further studies are needed to identify the underlying mechanisms.

Efficacy of Topical Immunoglobulins against Experimental Adenoviral Ocular Infection

Presently, there is no U.S. Federal Drug Administration (FDA)-approved antiviral therapy for the treatment of adenoviral (Ad) ocular infections. The goal of the present study was to determine the antiviral efficacy of human immunoglobulin (Ig), a preparation of highly purified and concentrated immunoglobulin (IgG) antibodies isolated from a large pool of human plasma donors, in vitro and on acute Ad replication in the Ad5 New Zealand White (NZW) rabbit ocular model. The antiviral activity of human Ig against multiple wild-type and human ocular isolates of adenovirus serotypes was investigated in vitro by using neutralizing assays in different human epithelial cell lines. In vivo bilateral topical ocular toxicity and antiviral efficacy were evaluated with established Ad5/NZW rabbit ocular models. In vivo Ig antiviral results were compared with those obtained with topical 0.5% cidofovir and saline. In three different epithelial cell lines, <or=6.25 mg/mL of the Ig neutralized several wild-type adenoviral serotypes that cause ocular infections. A dose of <or=10 mg/mL neutralized 88% of ocular isolates of the adenovirus serotypes. After treatment of infected animals, adenovirus-positive cultures per total cultures (days 1-14; P = 0.021), the duration of Ad5 shedding, (P = 0.008), and the mean combined ocular viral titer during the early (days 1-5; P = 0.0001) and the late (days 7-14; P = 0.013) phases of infection were significantly lower in Ig-treated animals than in saline-treated animals and were similar to those in cidofovir-treated animals. Ig demonstrated antiviral properties against multiple adenoviral serotypes in vitro and in the Ad5/NZW rabbit ocular model. Further studies are needed to advance topical immunoglobulin for treatment and prophylaxis of ocular infections.