scholarly journals Pneumocystis Pneumonia: Immunity, Vaccines, and Treatments

Pathogens ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 236
Author(s):  
Aaron D. Gingerich ◽  
Karen A. Norris ◽  
Jarrod J. Mousa
Keyword(s):  
Fungal Pathogen ◽  
Pneumocystis Pneumonia ◽  
Current Treatment ◽  
Treatment And Prevention ◽  
Immunodeficiency Virus ◽  
Life Threatening ◽  
Acquired Immunodeficiency ◽  
Opportunistic Fungal Pathogen ◽  
Immunodeficiency Disease

For individuals who are immunocompromised, the opportunistic fungal pathogen Pneumocystis jirovecii is capable of causing life-threatening pneumonia as the causative agent of Pneumocystis pneumonia (PCP). PCP remains an acquired immunodeficiency disease (AIDS)-defining illness in the era of antiretroviral therapy. In addition, a rise in non-human immunodeficiency virus (HIV)-associated PCP has been observed due to increased usage of immunosuppressive and immunomodulating therapies. With the persistence of HIV-related PCP cases and associated morbidity and mortality, as well as difficult to diagnose non-HIV-related PCP cases, an improvement over current treatment and prevention standards is warranted. Current therapeutic strategies have primarily focused on the administration of trimethoprim-sulfamethoxazole, which is effective at disease prevention. However, current treatments are inadequate for treatment of PCP and prevention of PCP-related death, as evidenced by consistently high mortality rates for those hospitalized with PCP. There are no vaccines in clinical trials for the prevention of PCP, and significant obstacles exist that have slowed development, including host range specificity, and the inability to culture Pneumocystis spp. in vitro. In this review, we overview the immune response to Pneumocystis spp., and discuss current progress on novel vaccines and therapies currently in the preclinical and clinical pipeline.

scholarly journals Antifungal activity of dendritic cell lysosomal proteins against Cryptococcus neoformans

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Benjamin N. Nelson ◽  
Savannah G. Beakley ◽  
Sierra Posey ◽  
Brittney Conn ◽  
Emma Maritz ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Cryptococcus Neoformans ◽  
Mammalian Cells ◽  
Cysteine Proteases ◽  
Dependent Manner ◽  
Life Threatening ◽  
Opportunistic Fungal Pathogen ◽  
Dose Dependent ◽  
Lysosomal Proteins

AbstractCryptococcal meningitis is a life-threatening disease among immune compromised individuals that is caused by the opportunistic fungal pathogen Cryptococcus neoformans. Previous studies have shown that the fungus is phagocytosed by dendritic cells (DCs) and trafficked to the lysosome where it is killed by both oxidative and non-oxidative mechanisms. While certain molecules from the lysosome are known to kill or inhibit the growth of C. neoformans, the lysosome is an organelle containing many different proteins and enzymes that are designed to degrade phagocytosed material. We hypothesized that multiple lysosomal components, including cysteine proteases and antimicrobial peptides, could inhibit the growth of C. neoformans. Our study identified the contents of the DC lysosome and examined the anti-cryptococcal properties of different proteins found within the lysosome. Results showed several DC lysosomal proteins affected the growth of C. neoformans in vitro. The proteins that killed or inhibited the fungus did so in a dose-dependent manner. Furthermore, the concentration of protein needed for cryptococcal inhibition was found to be non-cytotoxic to mammalian cells. These data show that many DC lysosomal proteins have antifungal activity and have potential as immune-based therapeutics.

scholarly journals Non-Hodgkin’s Plasmablastic Lymphoma as Initial Presentation of Human Immunodeficiency Virus

2021 ◽  
Vol 9 ◽  
pp. 232470962110146
Author(s):  
Roopam Jariwal ◽  
Nadia Raza ◽  
Janpreet Bhandohal ◽  
Everardo Cobos
Keyword(s):  
Human Immunodeficiency Virus ◽  
Acquired Immunodeficiency Syndrome ◽  
Initial Presentation ◽  
Plasmablastic Lymphoma ◽  
Healthy Male ◽  
Immunodeficiency Virus ◽  
Life Threatening ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Head Neck

Plasmablastic lymphoma (PBL) is a subtype of non-Hodgkin’s lymphoma that manifests in patients with the diagnosis of human immunodeficiency virus (HIV), more prominently in the head, neck, and oral mucosal region. The diagnosis of this rare lymphoma serves as a concomitant diagnosis of acquired immunodeficiency syndrome. The case is of a 33-year-old previously healthy male, with an unknown diagnosis of HIV with a painful right mandibular mass. He was subsequently diagnosed with PBL and HIV. This case of PBL illustrates the importance of linking a rare and potentially life-threatening diagnosis as a possible first manifestation of HIV.

HIV/AIDS and traditional healers: a blessing in disguise

2010 ◽  
Vol 50 (3) ◽  
pp. 154-155
Author(s):  
B L Meel
Keyword(s):  
Case Reports ◽  
Health Care Systems ◽  
Traditional Healers ◽  
Immunodeficiency Virus ◽  
Herbal Decoction ◽  
Care Systems ◽  
Life Threatening ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Hiv Aids

Traditional healers contribute significantly to the level of health-care systems in Africa. They could play an important role in the prevention and care of patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) in the community. The traditional healing system deals with psychosocial stress associated with HIV/AIDS as well as herbal medications. Sometimes, herbal medicine causes serious life-threatening complications. Two case reports are presented in this article. The first is a 48-year-old woman with HIV who was made to drink a large volume of a herbal decoction to stimulate vomiting in the belief that cleansing the bowel would rid the system of the disease. The second is a 25-year-old young man who had a herbal enema, which resulted in gangrene of the large bowel. The case histories, mechanism of action and causes of death are discussed.

scholarly journals Antidiabetic Effects of Hydroxytyrosol: In Vitro and In Vivo Evidence

Antioxidants ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 188 ◽  
Author(s):  
Filip Vlavcheski ◽  
Mariah Young ◽  
Evangelia Tsiani
Keyword(s):  
Insulin Resistance ◽  
Pathological Condition ◽  
Current Treatment ◽  
In Vivo Studies ◽  
Olive Leaves ◽  
Treatment And Prevention ◽  
Antidiabetic Effects

Insulin resistance, a pathological condition characterized by defects in insulin action leads to the development of Type 2 diabetes mellitus (T2DM), a disease which is currently on the rise that pose an enormous economic burden to healthcare systems worldwide. The current treatment and prevention strategies are considerably lacking in number and efficacy and therefore new targeted therapies and preventative strategies are urgently needed. Plant-derived chemicals such as metformin, derived from the French lilac, have been used to treat/manage insulin resistance and T2DM. Other plant-derived chemicals which are not yet discovered, may have superior properties to prevent and manage T2DM and thus research into this area is highly justifiable. Hydroxytyrosol is a phenolic phytochemical found in olive leaves and olive oil reported to have antioxidant, anti-inflammatory, anticancer and antidiabetic properties. The present review summarizes the current in vitro and in vivo studies examining the antidiabetic properties of hydroxytyrosol and investigating the mechanisms of its action.

scholarly journals Hemophagocytic Lymphohistiocytosis Associated With Parvovirus B19 in a Patient With Acquired Immunodeficiency Syndrome

2019 ◽  
Vol 7 ◽  
pp. 232470961988369
Author(s):  
Precious Macauley ◽  
Mohammad Abu-Hishmeh ◽  
Carissa Dumancas ◽  
Vijay Alexander-Rajan ◽  
Fernando Piedra-Chavez ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Parvovirus B19 ◽  
Signs And Symptoms ◽  
High Serum ◽  
Intrathecal Methotrexate ◽  
Immunodeficiency Virus ◽  
Threatening Condition ◽  
Life Threatening ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome

Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by widespread inflammation due to massive immune activation and cytokine release. It is of 2 types, primary or familial and secondary or acquired. Diagnosis is made by fulfilling 5 of 8 criteria as determined by the Histiocyte Society. Treatment includes etoposide, dexamethasone, with or without intrathecal methotrexate in the presence of neurologic involvement as well as treating the underlying cause in secondary HLH. We present a case of a 23-year-old female with congenital human immunodeficiency virus (HIV) infection who presents with nonspecific signs and symptoms of cough, fever, leukopenia, and anemia, and a high-serum parvovirus B19 DNA, later diagnosed with HLH and treated with etoposide and dexamethasone. She made clinical improvements and was successfully discharged to home after 26 days of admission.

scholarly journals Designer Nucleases: Gene-Editing Therapies using CCR5 as an Emerging Target in HIV

2019 ◽  
Vol 17 (5) ◽  
pp. 306-323 ◽  
Author(s):  
Maria João Almeida ◽  
Ana Matos
Keyword(s):  
Gene Editing ◽  
Leading Edge ◽  
Target Cells ◽  
Immunodeficiency Virus ◽  
Chemokine Receptor Ccr5 ◽  
Life Threatening ◽  
Promising Solution ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Receptor Ccr5

Acquired Immunodeficiency Syndrome (AIDS), caused by the Human Immunodeficiency Virus (HIV), is a life-threatening disorder that persists worldwide as a severe health problem. Since it was linked with the HIV attachment process, the Chemokine receptor, CCR5, has been at the development leading edge of several gene-based therapies. Given the shortcomings of the current antiretroviral treatment procedure and the non-availability of a licensed vaccine, the aptitude to modify complex genomes with Designer Nucleases has had a noteworthy impact on biotechnology. Over the last years, ZFN, TALEN and CRISPR/Cas9 gene-editing technology have appeared as a promising solution that mimics the naturally occurring CCR5/Δ32 mutation and permanently guarantees the absence of CCR5-expression on the surface of HIV target-cells, leading to a continuous resistance to the virus entry and, ultimately, proving that cellular immunization from infection could be, in fact, a conceivable therapeutic approach to finally achieve the long-awaited functional cure of HIV.

HIV-1 integrase inhibitors that block HIV-1 replication in infected cells. Planning synthetic derivatives from natural products

2003 ◽  
Vol 75 (2-3) ◽  
pp. 195-206 ◽  
Author(s):  
Roberto Di Santo ◽  
Roberta Costi ◽  
Marino Artico ◽  
E. Tramontano ◽  
P. La Colla ◽  
...  
Keyword(s):  
Natural Products ◽  
Clinical Approach ◽  
Strand Transfer ◽  
Immunodeficiency Virus ◽  
Infected Cells ◽  
Acquired Immunodeficiency ◽  
High Cytotoxicity ◽  
Immunodeficiency Syndrome ◽  
Hiv 1

Combination therapy using reverse transcriptase (RT) and protease (PR) inhibitors is currently the best clinical approach in combatting acquired immunodeficiency syndrome (AIDS), caused by infection from the human immunodeficiency virus type 1 (HIV-1). However, the emergence of resistant strains calls urgently for research on inhibitors of further viral targets such as integrase (IN), the enzyme that catalyzes the integration of the proviral DNA into the host chromosomes. Recently, we started studies on new IN inhibitors as analogs of natural products, characterized by one or two 3,4-dihydroxycinnamoyl moieties, which were proven to be IN inhibitors in vitro. Then, we designed and synthesized a number of derivatives sharing 3,4 dihydroxycinnamoyl groups, obtaining potent IN inhibitors active at submicromolar concentrations. Unfortunately, these derivatives lacked antiretroviral activity, probably owing to their high cytotoxicity. So we designed a number of 3,4,5-trihydroxycinnamoyl derivatives as less-cytotoxic IN inhibitors, which were proven to be antiretrovirals in cell-based assays. Finally, we designed and synthesized a number of aryldiketohexenoic acids, strictly related to the aryldiketo acid series recently reported by Merck Company, which were shown to be potent antiretroviral agents endowed with anti-IN activities either in 3' processing or in strand transfer steps.

scholarly journals yKu70/yKu80 and Rif1 Regulate Silencing Differentially at Telomeres in Candida glabrata

2008 ◽  
Vol 7 (12) ◽  
pp. 2168-2178 ◽  
Author(s):  
Lluvia L. Rosas-Hernández ◽  
Alejandro Juárez-Reyes ◽  
Omar E. Arroyo-Helguera ◽  
Alejandro De Las Peñas ◽  
Shih-Jung Pan ◽  
...  
Keyword(s):  
Fungal Pathogen ◽  
Candida Glabrata ◽  
Large Family ◽  
Reporter Genes ◽  
Cell Wall Proteins ◽  
Intergenic Regions ◽  
Reporter Strains ◽  
Opportunistic Fungal Pathogen ◽  
Subtelomeric Regions

ABSTRACT Candida glabrata, a common opportunistic fungal pathogen, adheres efficiently to mammalian epithelial cells in culture. This interaction in vitro depends mainly on the adhesin Epa1, one of a large family of cell wall proteins. Most of the EPA genes are located in subtelomeric regions, where they are transcriptionally repressed by silencing. In order to better characterize the transcriptional regulation of the EPA family, we have assessed the importance of C. glabrata orthologues of known regulators of subtelomeric silencing in Saccharomyces cerevisiae. To this end, we used a series of strains containing insertions of the reporter URA3 gene within different intergenic regions throughout four telomeres of C. glabrata. Using these reporter strains, we have assessed the roles of SIR2, SIR3, SIR4, HDF1 (yKu70), HDF2 (yKu80), and RIF1 in mediating silencing at four C. glabrata telomeres. We found that, whereas the SIR proteins are absolutely required for silencing of the reporter genes and the native subtelomeric EPA genes, the Rif1 and the Ku proteins regulate silencing at only a subset of the analyzed telomeres. We also mapped a cis element adjacent to the EPA3 locus that can silence a reporter gene when placed at a distance of 31 kb from the telomere. Our data show that silencing of the C. glabrata telomeres varies from telomere to telomere. In addition, recruitment of silencing proteins to the subtelomeres is likely, for certain telomeres, to depend both on the telomeric repeats and on particular discrete silencing elements.

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