scholarly journals Caerin 1 Antimicrobial Peptides that Inhibit HIV and Neisseria May Spare Protective Lactobacilli

Antibiotics ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 661 ◽  
Author(s):  
Louise A. Rollins-Smith ◽  
Patricia B. Smith ◽  
Anna M. Ledeczi ◽  
Julia M. Rowe ◽  
Laura K. Reinert
Keyword(s):  
Antimicrobial Peptides ◽  
Lactobacillus Rhamnosus ◽  
Close Relative ◽  
Neisseria Lactamica ◽  
Vaginal Lactobacilli ◽  
Low Concentrations ◽  
Low Toxicity ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome

Although acquired immunodeficiency syndrome (AIDS) caused by the human immunodeficiency virus (HIV) is a manageable disease for many, it is still a source of significant morbidity and economic hardship for many others. The predominant mode of transmission of HIV/AIDS is sexual intercourse, and measures to reduce transmission are needed. Previously, we showed that caerin 1 antimicrobial peptides (AMPs) originally derived from Australian amphibians inhibited in vitro transmission of HIV at relatively low concentrations and had low toxicity for T cells and an endocervical cell line. The use of AMPs as part of microbicidal formulations would expose the vaginal microbiome to these agents and cause potential harm to protective lactobacilli. Here, we tested the effects of caerin 1 peptides and their analogs on the viability of two species of common vaginal lactobacilli (Lactobacillus rhamnosus and Lactobacillus crispatus). Several candidate peptides had limited toxicity for the lactobacilli at a range of concentrations that would inhibit HIV. Three AMPs were also tested for their ability to inhibit growth of Neisseria lactamica, a close relative of the sexually transmissible Neisseria gonorrhoeae. Neisseria lactamica was significantly more sensitive to the AMPs than the lactobacilli. Thus, several candidate AMPs have the capacity to inhibit HIV and possible N. gonorrhoeae transmission at concentrations that are significantly less harmful to the resident lactobacilli.

scholarly journals Different effect of benzylacyclouridine on the toxic and therapeutic effects of azidothymidine in mice

Blood ◽  
1990 ◽  
Vol 76 (11) ◽  
pp. 2216-2221 ◽  
Author(s):  
A Falcone ◽  
JW Darnowski ◽  
RM Ruprecht ◽  
SH Chu ◽  
I Brunetti ◽  
...  
Keyword(s):  
Leukemia Virus ◽  
Hematologic Toxicity ◽  
Therapeutic Effects ◽  
Dependent Manner ◽  
Aids Related Complex ◽  
Effective Doses ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
Oral Doses

Abstract It has been reported that in vitro uridine (Urd) can reverse azidothymidine (AZT) cytotoxicity without decreasing anti-human immunodeficiency virus (HIV) activity. Our studies in mice have shown that daily oral doses of benzylacyclouridine (BAU), an inhibitor of Urd breakdown, also reduces AZT hematologic toxicity, presumably by elevating the plasma concentration of Urd. We now extend these murine studies and report the effect of various doses of exogenous Urd, various doses of BAU, or the combination of BAU and Urd, administered daily, on AZT-induced toxicity. In mice receiving concomitant AZT, daily doses of Urd of 1,000 to 2,000 mg/kg increase peripheral reticulocytes and slightly reduce AZT-induced hematologic toxicity. However, the range of effective doses is narrow, and higher doses of Urd (greater than 3,000 mg/kg/d) significantly enhance hematologic toxicity. At its most effective dose, (2,000 mg/kg/d), Urd produces 28% mortality. In contrast, BAU doses up to 300 mg/kg/d reduced AZT-related hematologic toxicity in a dose-dependent manner without mortality. Higher daily doses of BAU and the combination of BAU with low doses of Urd were not more effective. Studies conducted in mice infected with the Rauscher murine leukemia virus (RLV) indicate that BAU does not impair the antiretroviral effect of AZT when administered at doses that reduce AZT-induced anemia and leukopenia. These findings may be significant for the treatment of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex.

Rapid Death of Adoptively Transferred T Cells in Acquired Immunodeficiency Syndrome

Blood ◽  
1999 ◽  
Vol 93 (5) ◽  
pp. 1506-1510 ◽  
Author(s):  
Rusung Tan ◽  
Xiaoning Xu ◽  
Graham S. Ogg ◽  
Pokrath Hansasuta ◽  
Tao Dong ◽  
...  
Keyword(s):  
T Cell ◽  
Adoptive Transfer ◽  
Acquired Immunodeficiency Syndrome ◽  
Mononuclear Cells ◽  
Virus Load ◽  
Acquired Immunodeficiency ◽  
Peptide Complexes ◽  
Immunodeficiency Syndrome

Human immunodeficiency virus (HIV)-specific cytotoxic T lymphocytes (CTL) probably play the major role in controlling HIV replication. However, the value of adoptive transfer of HIV-specific CTL expanded in vitro to HIV+ patients has been limited: this contrasts with the success of CTL therapy in treating or preventing Epstein-Barr virus and cytomegalovirus disease after bone marrow transplantation (BMT). We investigated the fate of expanded HIV-specific CTL clones in vivo following adoptive transfer to a patient with acquired immunodeficiency syndrome (AIDS). Two autologous CTL clones specific for HIV Gag and Pol were expanded to large numbers (>109) in vitro and infused into an HIV-infected patient whose viral load was rising despite antiretroviral therapy. The fate of one clone was monitored by staining peripheral blood mononuclear cells (PBMCs) with T-cell receptor–specific tetrameric major histocompatibility complex (MHC)-peptide complexes. Although the CTL transfer was well tolerated, there were no significant changes in CD4 and CD8 lymphocyte counts and virus load. By tracking an infused clone using soluble MHC-peptide complexes, we show that cells bearing the Gag-specific T-cell receptors were rapidly eliminated within hours of infusion through apoptosis. Thus, the failure of adoptively transferred HIV-specific CTL to reduce virus load in AIDS may be due to rapid apoptosis of the infused cells, triggered by a number of potential mechanisms. Further trials of adoptive transfer of CTL should take into account the susceptibility of infused cells to in vivo apoptosis.

scholarly journals Production of and in vitro response to interleukin 2 in the acquired immunodeficiency syndrome.

1985 ◽  
Vol 76 (5) ◽  
pp. 1959-1964 ◽  
Author(s):  
H W Murray ◽  
K Welte ◽  
J L Jacobs ◽  
B Y Rubin ◽  
R Mertelsmann ◽  
...  
Keyword(s):  
Acquired Immunodeficiency Syndrome ◽  
Interleukin 2 ◽  
In Vitro Response ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome

scholarly journals In Vitro Susceptibility of Talaromyces Marneffei In Malaysia: Comparison of Yeast and Mycelial Phases

2021 ◽  
Author(s):  
Xue Ting Tan ◽  
Nurliyana binti Mohd Shuhairi ◽  
Stephanie Jane Ginsapu ◽  
Surianti Binti Shukor ◽  
Fairuz Binti Amran
Keyword(s):  
Amphotericin B ◽  
Geometric Mean ◽  
Antifungal Susceptibility ◽  
Etiologic Agent ◽  
Mycelial Form ◽  
In Vitro Susceptibility ◽  
Terbinafine Hydrochloride ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome

Abstract Talaromyces marneffei is an etiologic agent of talaromycosis. It can cause serious complications and death in immunocompromised patients, particularly in acquired immunodeficiency syndrome (AIDS) patients. This infectious disease is endemic in Southeast Asia including Malaysia. To date, published reports on the antifungal susceptibility profile of T. marneffei is very limited. The objective of this study is to determine the minimum inhibitory concentration (MIC) of T. marneffei in yeast and mycelial phases in Malaysia. In the year 2020, 27 clinical strains of T. marneffei were received from various hospitals in Malaysia. The identification was carried out using microscopic, macroscopic and molecular methods. Following that, the susceptibility of each isolate in both yeast and mycelial form to thirteen common antifungals was performed according to the broth microdilution in Clinical & Laboratory Standards Institute (CLSI) M38 method. The antifungals tested were anidulafungin, micafungin sodium, caspofungin diacetate, 5-fluorocytosine, amphotericin B and terbinafine hydrochloride, posaconazole, voriconazole, itraconazole, ketoconazole, ravuconazole, clotrimazole and isavuconazole. The geometric mean of all antifungals other than anidulafungin, micafungin sodium, caspofungin diacetate and 5-fluorocytosine against T. marneffei mould (mycelial) were >2 μg/ml. However, the geometric mean of all antifungals against T. marneffei yeast was <2 μg/ml. Our in vitro data suggests promising activities of amphotericin B, terbinafine hydrochloride, posaconazole, voriconazole, itraconazole, ketoconazole, ravuconazole, clotrimazole and isavuconazole against yeast and mould phases of T. marneffei.

Activation of monocyte-mediated tumoricidal activity in patients with acquired immunodeficiency syndrome.

1985 ◽  
Vol 3 (7) ◽  
pp. 1005-1012 ◽  
Author(s):  
E S Kleinerman ◽  
L M Ceccorulli ◽  
L A Zwelling ◽  
T Twilley ◽  
R B Herberman ◽  
...  
Keyword(s):  
Acquired Immunodeficiency Syndrome ◽  
Mononuclear Cells ◽  
Human Tumor ◽  
Target Cells ◽  
Aids Patients ◽  
Tumoricidal Activity ◽  
Ifn Gamma ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome

The purpose of these studies was to determine whether peripheral blood monocytes from acquired immunodeficiency syndrome (AIDS) patients with Kaposi's sarcoma could be activated to lyse human tumor target cells in vitro. Monocytes were isolated and incubated for 24 hours in vitro with either medium (control), a crude mitogen-induced lymphokine preparation (MAF), or endotoxin before the addition of [125I]IUdR-labeled A375 melanoma target cells. Cytolysis was determined 72 hours later. Twelve (100%) of 12 patients tested had monocyte-mediated cytotoxicity values that were comparable to those of normal individuals. Recombinant human gamma interferon (IFN gamma) activated both normal and AIDS monocyte-mediated tumoricidal function only when combined with lypopolysaccharide (LPS). In addition, mononuclear cells from ten AIDS patients were also tested for their ability to secrete MAF and IFN gamma in response to a mitogenic stimulus. Lymphokines generated from all ten patients contained substantial amounts of IFN gamma (100 to 2,500 U/mL); however, three of these ten lymphokine preparations failed to activate normal monocytes to lyse tumor cells. These results suggest that monocyte-mediated tumoricidal function of AIDS patients is intact and thus suggest new approaches for the therapy of AIDS.

Pentamidine: A Review

1991 ◽  
Vol 12 (6) ◽  
pp. 375-382 ◽  
Author(s):  
Michael W. Scheld ◽  
Brian Wispelwey ◽  
Richard D. Pearson
Keyword(s):  
High Risk ◽  
Clinical Results ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy ◽  
Aerosolized Pentamidine ◽  
Pentamidine Isethionate ◽  
Low Toxicity ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome

With the advent of the acquired immunodeficiency syndrome (AIDS), the therapeutic importance of pentamidine isethionate has increased greatly. This review summarizes the pharmacology, clinical experience in the treatment of Pneumocystis carinii pneumonia, and toxicity of pentamidine. Data are conflicting as to whether pentamidine is more or less effective than trimethoprim-sulfamethoxazole (TMP-SX) for the treatment of P carinii pneumonia in individuals with AIDS, but due to its toxicity and expense, it is considered as second-line therapy for P carinii pneumonia by many authorities. Hypoglycemia has been encountered in up to 27%, and nephrotoxicity in 25%, of treatment courses with pentamidine. In an attempt to circumvent the toxicities associated with parenteral administration, aerosolized delivery has been evaluated for both therapy and prevention of P carinii pneumonia. Aerosolized pentamidine, on the basis of early clinical results, convenience, and low toxicity, is being used extensively to prevent P carinii pneumonia in individuals at high risk. Relapses occur, however, and pneumothorax may be more common in those using this form of prophylaxis. Aerosolized pentamidine should not be used as sole therapy for acute P carinii pneumonia.

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 Disseminated cryptococcosis and fluconazole resistant oral candidiasis in a patient with acquired immunodeficiency syndrome (AIDS)

2010 ◽  
Vol 4 (10) ◽  
pp. 674-678 ◽  
Author(s):  
Rajendra J Kothavade ◽  
Chetan M Oberai ◽  
Arvind G Valand ◽  
Mehroo H Panthaki
Keyword(s):  
Oral Candidiasis ◽  
Drug Susceptibility ◽  
Drug Susceptibility Testing ◽  
Body Parts ◽  
Root Cause ◽  
Fluconazole Resistant ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome ◽  
In Vitro Drug Susceptibility

Disseminated cryptococcosis and recurrent oral candidiasis was presented in a-heterosexual AIDS patient. Candida tropicalis (C.tropicalis) was isolated from the oral pseudomembranous plaques and Cryptococcus neoformans (C. neoformans) was isolated from maculopapular lesions on body parts (face, hands and chest) and body fluids (urine, expectorated sputum, and cerebrospinal fluid). In vitro drug susceptibility testing on the yeast isolates demonstrated resistance to fluconazole acquired by C. tropicalis which was a suggestive possible root cause of recurrent oral candidiasis in this patient.

ANTIVIRAL ACTIVITY OF HERBAL IMMUNOMODULATORY PREPARATIONS NCV I AND AC II – AND THEIR USEFULNESS IN HIV INFECTION

INDIAN DRUGS ◽  
2015 ◽  
Vol 52 (11) ◽  
pp. 50-55
Author(s):  
S. T Tharakan ◽  
◽  
P. P. Binitha ◽  
R. Kuttan ◽  
G. Kuttan
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiviral Activity ◽  
Vero Cells ◽  
Chick Embryos ◽  
The Past ◽  
Immunodeficiency Virus ◽  
Acquired Immunodeficiency ◽  
Immunodeficiency Syndrome

NCV I and AC II are the two herbal immunomodulatory preparations being used in our centre for the treatment of acquired immunodeficiency syndrome (AIDS) for the past 20 years. The objective of this study is to check whether these drugs possess any antiviral activity in vitro and in vivo. In vitro antiviral activity was determined using Vero cells against Poliovirus. In vivo antiviral activity was determined in chick and duck embryonated eggs using New Castle Disease Virus (NDV), Egg Drop Syndrome (EDS) virus and also in NDV vaccinated chicks. NCV I and AC II decreased growth of poliovirus in culture. When the virus-inoculated Vero cells were treated with NCV I, the viral growth was inhibited by 59.87% and with AC II it was inhibited by 70.06%. When the chick embryos were treated with these viruses, there was no immediate lethality for 5 days but the haemagglutination titre (HA) was found to be significantly increased indicating an increase in viral load. The haemagglutination titre for NDV alone was found to be 1024 against normal untreated value of 128. In EDS treated duck eggs HA titre was found to be 4096. These titres were reduced to 4 in NCV I and 8 in AC II treated duck embryos. NCV I and AC II were also found to decrease the HA titre in chicks treated with NDV. These studies indicated the effectiveness of NCV I and AC II in HIV could be partially due to its antiviral activity against human immunodeficiency virus.

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