Metabolic Deficiencies Underlie Plasmacytoid Dendritic Cell Exhaustion After Viral Infection.

Type I Interferons (IFN-I) are central to host protection against viral infections . While any cell can produce IFN-I, Plasmacytoid Dendritic Cells (pDCs) make greater quantities and more varieties of these cytokines than any other cell type . However, following an initial burst of IFN- I, pDCs lose their exceptional IFN-I production capacity and become "exhausted", a phenotype that associates with enhanced susceptibility to secondary infections .

Interferon induction, evasion, and paradoxical roles during SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), has caused millions of deaths in the past two years. Although initially little was understood about this virus, recent research has significantly advanced and landed interferons (IFNs) in the spotlight. While Type I and III IFN have long been known as central to antiviral immunity, in the case of COVID-19 their role was initially controversial.

Virus-based vaccine vectors with distinct replication mechanisms differentially infect and activate dendritic cells.

The precise mechanism by which many virus-based vectors activate immune responses remains unknown. Dendritic cells (DCs) play key roles in priming T cell responses and controlling virus replication, but their functions in generating protective immunity following vaccination with viral vectors are not always well understood. We hypothesized that highly immunogenic viral vectors with identical cell entry pathways but unique replication mechanisms differentially infect and activate DCs to promote antigen presentation and activation of distinctive antigen-specific T cell responses.

Innate immunity and HBV persistence.

Hepatitis B virus (HBV) causes chronic infections that are associated with immune dysfunction. Though T cell impairment is perhaps the most prominent immune change contributing to viral persistence, HBV interaction with the innate immune system is also likely key, as the lack of effective innate immunity has functional consequences that promote chronic infection. In addition to an intrinsic ability to fight viral infections, the innate immune system also impacts T cell responses and other adaptive immune mechanisms critical for HBV control.

Human hydatid cyst fluid-induced therapeutic anti-cancer immune responses via NK1.1 cell activation in mice.

Echinococcus granulosus is a cestode parasite which causes cystic echinococcosis disease. Previously we observed that vaccination with E. granulosus antigens from human hydatid cyst fluid (HCF) significantly inhibits colon cancer growth.

Modified Alphavirus-Vesiculovirus Hybrid Vaccine Vectors for Homologous Prime-Boost Immunotherapy of Chronic Hepatitis B.

Virus-like vesicles (VLV) are hybrid vectors based on an evolved Semliki Forest virus (SFV) RNA replicon and the envelope glycoprotein (G) from vesicular stomatitis virus (VSV) [...

Virus-like Vesicles Expressing Multiple Antigens for Immunotherapy of Chronic Hepatitis B.

Infections with hepatitis B virus (HBV) can initiate chronic hepatitis and liver injury, causing more than 600,000 deaths each year worldwide. Current treatments for chronic hepatitis B are inadequate and leave an unmet need for immunotherapeutic approaches. We designed virus-like vesicles (VLV) as self-amplifying RNA replicons expressing three HBV antigens (polymerase, core, and middle surface) from a single vector (HBV-VLV) to break immune exhaustion despite persistent HBV replication.

Mechanisms of Innate Immune Activation by a Hybrid Alphavirus-Rhabdovirus Vaccine Platform.

Virus-like vesicles (VLV) are infectious, self-propagating alphavirus-vesiculovirus hybrid vaccine vectors that can be engineered to express foreign antigens to elicit a protective immune response. VLV are highly immunogenic and nonpathogenic , and we hypothesize that the unique replication and structural characteristics of VLV efficiently induce an innate antiviral response that enhances immunogenicity and limits replication and spread of the vector. We found that VLV replication is inhibited by interferon (IFN)-α, IFN-γ, and IFN-λ, but not by tumor necrosis factor-α.

Heterologous prime-boost immunization with vesiculovirus-based vectors expressing HBV Core antigen induces CD8 T cell responses in naïve and persistently infected mice and protects from challenge.

Chronic hepatitis B virus (HBV) infections cause more than 800,000 deaths per year and currently approved treatments do not cure the disease. Because a hallmark of acute infection resolution is the presence of functional CD8 T cells to the virus, activation of the immune system with therapeutic vaccines represents a potential approach for treating chronic hepatitis B. In this study, we evaluated the immunogenicity and efficacy of two attenuated vesiculovirus-based platforms expressing HBV Core antigen, the highly attenuated vesicular stomatitis virus (VSV) N4CT1 and a unique vaccine platform [virus-like vesicles (VLV)] that is based on a Semliki Forest virus replicon expressing the VSV glycoprotein.

A Highly Attenuated Vesicular Stomatitis Virus-Based Vaccine Platform Controls Hepatitis B Virus Replication in Mouse Models of Hepatitis B.

Therapeutic vaccines may be an important component of a treatment regimen for curing chronic hepatitis B virus (HBV) infection. We previously demonstrated that recombinant wild-type vesicular stomatitis virus (VSV) expressing the HBV middle surface glycoprotein (MHBs) elicits functional immune responses in mouse models of HBV replication. However, VSV has some undesirable pathogenic properties, and the use of this platform in humans requires further viral attenuation.

A mucin-like peptide from Fasciola hepatica induces parasite-specific Th1-type cell immunity.

Fasciolosis, caused by the liver fluke Fasciola hepatica, is a major parasitic disease of livestock that causes significant economic losses worldwide. Although drugs are effective against liver flukes, they do not prevent reinfection, and continuous treatment is costly. Moreover, resistant fluke strains are emerging.

Trypanosoma cruzi extracts elicit protective immune response against chemically induced colon and mammary cancers.

Trypanosoma cruzi, the protozoan parasite that causes Chagas' disease, has anticancer effects mediated, at least in part, by parasite-derived products which inhibit growth of tumor cells. We investigated whether immunity to T. cruzi antigens could induce antitumor activity, using two rat models which reproduce human carcinogenesis: colon cancer induced by 1,2-dimethylhydrazine (DMH), and mammary cancer induced by N-nitroso-N-methylurea (NMU).

Mucin-like peptides from Echinococcus granulosus induce antitumor activity.

There is substantial evidence suggesting that certain parasites can have antitumor properties. We evaluated mucin peptides derived from the helminth Echinococcus granulosus (denominated Egmuc) as potential inducers of antitumor activity. We present data showing that Egmuc peptides were capable of inducing an increase of activated NK cells in the spleen of immunized mice, a fact that was correlated with the capacity of splenocytes to mediate killing of tumor cells.

Transepithelial transport of biperiden hydrochloride in Caco-2 cell monolayers.

The aim of this research has been to determine the biperiden hydrochloride permeability in Caco-2 model, in order to classify it based on the Biopharmaceutics Classification System (BCS). The World Health Organization (WHO) as well as many other authors have provisionally assigned the drug as BCS class I (high solubility-high permeability) or III (high solubility-low permeability), based on different methods. We determined biperiden BCS class by comparing its permeability to 5 pre-defined compounds: atenolol and ranitidine hydrochloride (low permeability group) and metoprolol tartrate, sodium naproxen and theophylline (high permeability group).

Aeromonas hydrophila and its relation with drinking water indicators of microbiological quality in Argentine.

In Argentine, water municipal supplies disinfection is carried out by chlorine. We have isolated Aeromonas hydrophila from a chlorinated water supply in Buenos Aires that fulfilled Argentinean microbiological quality standards. It is an aquatic organism that could produce cytotoxins and enterotoxins associated with acute gastroenteritis and wound infections in human and hemorrhagic septicaemia of fish, reptiles and amphibians.

[Recombinant human erythropoietin: method of in vivo evaluation using normocythemic mice].

Purpose: The implementation of an in vivo assay to determine the biological activity of human recombinant erythropoietin (Hu-r EPO) is essential. The purpose of this study was to perform and optimize the conditions of an easy in vivo bioassay suitable for routine testing of quality control of Hu-r EPO preparations.

Material And Methods: Normocythemic 8 weeks female mice treated with different Hu-r EPO doses were employed.

Search for related substances in market products containing enalapril maleate as the active principle.

This study's main object was the determination of substances, by means of high-performance liquid chromatography (HPLC), that are related to enalapril maleate in medicinal tablets. The research was on products containing a 20 mg active principle with a 12-month delta t and on those batches near their expiration date with an enalapril maleate concentration of 10, 5, and 2.5 mg.

Stability of pilocarpine ophthalmic solutions.

The stability of pilocarpine and pilocarpine-timolol eyedrop preparations available on the Argentine market was studied. A high-performance liquid chromatographic method that allows the estimation of pilocarpine in the presence of degradation products was used for the study according to the preestablished design. It was found that pilocarpine solutions are stable, while pilocarpine in association with timolol shows significant degradation.

Fungal and aflatoxin contamination of medicinal herbs.

Since the consumption of aromatic and medicinal herbs has been increasing in the last years, the Argentinian Health Authorities are concerned to control the quality and security of them. Fungal and aflatoxin contamination are two parameters to be taken into account, to ensure the harmlessness of the phytomedicinal products. In 81 different samples, grouped in end products (EP), raw material (RM) and at harvest (SH), fungal flora (enumeration and identification) as well as naturalAspergillus flavus and aflatoxin occurrence were investigated.

Preparation of norfloxacin spherical agglomerates using the ammonia diffusion system.

Agglomerated crystals of norfloxacin were prepared by a spherical crystallization technique using the ammonia diffusion system (ADS). This technique makes it possible to agglomerate amphoteric drugs like norfloxacin, which cannot be agglomerated by conventional procedures. When an ammonia-water solution of norfloxacin is poured into an acetone dichloromethane mixture under agitation, a small amount of ammonia is liberated in the system.

Sanitary factors and mycotoxin contamination in the argentinian wheat crop 1993/94.

In Argentina, due to climatic conditions, Fusarium head blight (FHB) caused by Fusarium graminearum, affected the 1993/94 wheat crop. To evaluate the severity of this disease, samples of wheat where gathered from four zones of the wheat area. Sanitary conditions and mycotoxin contamination were determined.