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2.
Sci Rep ; 11(1): 2754, 2021 02 02.
Article in English | MEDLINE | ID: mdl-33531523

ABSTRACT

Assessments of ecosystem service and function losses of wetlandscapes (i.e., wetlands and their hydrological catchments) suffer from knowledge gaps regarding impacts of ongoing hydro-climatic change. This study investigates hydro-climatic changes during 1976-2015 in 25 wetlandscapes distributed across the world's tropical, arid, temperate and cold climate zones. Results show that the wetlandscapes were subject to precipitation (P) and temperature (T) changes consistent with mean changes over the world's land area. However, arid and cold wetlandscapes experienced higher T increases than their respective climate zone. Also, average P decreased in arid and cold wetlandscapes, contrarily to P of arid and cold climate zones, suggesting that these wetlandscapes are located in regions of elevated climate pressures. For most wetlandscapes with available runoff (R) data, the decreases were larger in R than in P, which was attributed to aggravation of climate change impacts by enhanced evapotranspiration losses, e.g. caused by land-use changes.

3.
Ann Pharm Fr ; 69(5): 258-64, 2011 Sep.
Article in French | MEDLINE | ID: mdl-21924126

ABSTRACT

In January 2008, fatal anaphylactoid reaction (AR) was found to be associated with oversulfated chondroitin sulphate (OSCS) contaminated heparin. Although attributed to bradykinin released during contact system activation by OSCS, no final evidence until now exists for a bradykinin release during incubation of contaminated heparin with human plasma. The first objective of our study was to measure and to characterize the kinetic profile of bradykinin release in human plasma incubated with OSCS and contaminated heparin. As these AR occurred mainly in the first minutes of the dialysis session, we examine the different factors likely to influence the kinin-forming capacity of OSCS: dilution of plasma, presence of an angiotensin converting enzyme inhibitor, capacity of the patient to metabolise kinins.


Subject(s)
Anaphylaxis/chemically induced , Anticoagulants/adverse effects , Chondroitin Sulfates/adverse effects , Drug Contamination , Heparin/adverse effects , Aminopeptidases/metabolism , Anaphylaxis/metabolism , Angiotensin-Converting Enzyme Inhibitors/analysis , Anticoagulants/chemistry , Anticoagulants/therapeutic use , Bradykinin/blood , China , Chondroitin Sulfates/analysis , Dialysis , Heparin/chemistry , Heparin/therapeutic use , Humans , Kinins/metabolism , Sulfates/analysis
4.
Ann Pharm Fr ; 67(3): 169-72, 2009 May.
Article in French | MEDLINE | ID: mdl-19446665

ABSTRACT

Severe hypersensitivity reactions have been reported with bolus injection of heparin contaminated with oversulfated chondroitin sulphate, which has been shown to activate the plasma contact system. In this paper, we parallel the pathophysiology of these acute side effects with this of hypersensitivity reaction during hemodialysis or blood product transfusion in patients treated with an angiotensin converting enzyme inhibitor.


Subject(s)
Anticoagulants/adverse effects , Drug Hypersensitivity/physiopathology , Heparin/adverse effects , Angiotensin-Converting Enzyme Inhibitors/adverse effects , Blood Transfusion , Chemistry, Pharmaceutical , China , Chondroitin Sulfates/adverse effects , Humans , Renal Dialysis
5.
Bull Soc Pathol Exot ; 98(2): 127-32, 2005 Jun.
Article in French | MEDLINE | ID: mdl-16050381

ABSTRACT

A survey on intestinal helminths in school children was conducted in Haiti in 2002. This first nationwide study involving the entire country was stratified by department according to urban and rural zones using the cluster method. Focusing on elementary school children (n=5792; age range 3 to 20 years), it involved 26 urban and 49 rural schools randomly selected. Stools were preserved in formalin and examined by the Ritchie technique. Thirty-four per cent of stools (1981/5792) tested positive for intestinal helminths with the following parasites identified: Ascaris lumbricoides (27.3%), Trichuris trichiura (7.3%), Necator americanus (3.8%), Hymenolepsis nana (2%), Taenia sp. (0.3%) and Strongyloides stercoralis (0.2%). The helminth prevalence was higher in rural (38.4%) compared to urban areas (30%). There was no significant difference in prevalence by sex and age. The importance of geohelminths changed from one department to another with the highest prevalence found in the Southern department of Grande Anse (73.7%) and the lowest prevalence in the Center department (20.6%). Five out of the country's nine departments had a similar prevalence varying from 25.5% to 28.2%. Intestinal helminthic polyparasitism was observed in a percentage of infested school children comprise between 3.4% and 28.6% according in relation to the geographical area. A program to fight against geohelminths in school children should be initiated as a public health priority. Albendazole is the drug of choice. Frequency of drug distribution should be based on the prevalence of geohelminths in each department.


Subject(s)
Helminthiasis/epidemiology , Intestinal Diseases, Parasitic/epidemiology , Adolescent , Adult , Animals , Ascaris lumbricoides/isolation & purification , Child , Child, Preschool , Haiti/epidemiology , Helminthiasis/parasitology , Humans , Hymenolepis nana/isolation & purification , Intestinal Diseases, Parasitic/parasitology , Necator americanus/isolation & purification , Rural Population , Strongyloides stercoralis/isolation & purification , Students , Taenia/isolation & purification , Trichuris/isolation & purification , Urban Population
6.
Opt Lett ; 29(24): 2887-9, 2004 Dec 15.
Article in English | MEDLINE | ID: mdl-15645813

ABSTRACT

By recording low-pressure absorption lines of N2O around 3.9 microm, we fully qualify a pulsed entangled-cavity doubly resonant optical parametric oscillator as a power tool for high-resolution spectroscopy. This compact source runs at a high repetition rate (>10 kHz) with a low threshold of oscillation (<8 microJ), is mode-hop-free tunable over 5 cm(-1), and displays single-frequency Fourier-transformed-limited operation (linewidth <0.005 cm(-1)). A high potential for nonlinear spectroscopy is also expected given the high peak power (70 W) and the good quality (M2 < 2) of the output beam.

7.
Curr Drug Targets ; 3(1): 17-30, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11899262

ABSTRACT

The number of individuals infected with human immunodeficiency virus (HIV) and other pathogens causing sexually transmitted diseases (STDs) is growing dramatically worldwide. Globally, heterosexual transmission may account for as much as 85-90% of new cases of HIV infection. Latex condoms represent an effective barrier against sexually transmitted pathogens, but unfortunately, their use is not generalized. Therefore, there is an urgent need to develop safe and potent topical microbicides under the control of women to efficiently reduce the spread of sexually transmitted infections. Sodium lauryl sulfate (SLS), an anionic surfactant with protein denaturing potency, is a potent inhibitor of the infectivity of several enveloped (Herpes simplex viruses, HIV-1, Semliki Forest virus) and nonenveloped (papillomaviruses, reovirus, rotavirus and poliovirus) viruses. The mechanism of action of SLS involves the solubilization of the viral envelope and/or the denaturation of envelope and/or capsid proteins. Studies have shown that SLS is not toxic for cultured cell lines of different origins at concentrations that inactivate HIV-1, herpes and human papillomavirus in vitro. In addition, intravaginal pretreatment of mice with a gel formulation containing SLS, completely protected animals against Herpes simplex virus type-2 infection. The gel formulation containing SLS was also well-tolerated following repeated intravaginal administrations to rabbits. Taken together, these data suggest that SLS represents a potential candidate for the use as a topical microbicide to prevent the sexual transmission of HIV-1, herpes, human papillomavirus and possibly other sexually transmitted pathogens. The impact of such a preventive tool on public health can be enormous.


Subject(s)
Antiviral Agents/pharmacology , Sodium Dodecyl Sulfate/pharmacology , Viral Envelope Proteins/metabolism , Animals , Antiviral Agents/therapeutic use , HIV-1/drug effects , Humans , Papillomaviridae/drug effects , Protein Denaturation/drug effects , Simplexvirus/drug effects , Sodium Dodecyl Sulfate/therapeutic use , Surface-Active Agents/pharmacology , Surface-Active Agents/therapeutic use , Virus Activation/drug effects
8.
Opt Lett ; 27(14): 1238-40, 2002 Jul 15.
Article in English | MEDLINE | ID: mdl-18026414

ABSTRACT

We report a pulsed doubly resonant optical parametric oscillator that uses an original entangled-cavity geometry. This compact source (total volume of 1 L, including the pump laser) displays single-frequency operation (linewidth, <100 MHz), a high repetition rate (>10 kHz), low threshold (<10 muJ), and wide tuning in the mid-infrared. These properties qualify pulsed doubly resonant optical parametric oscillators as powerful tools for applications in such fields as nonlinear spectroscopy, lidar, and pollutant detection.

9.
Antimicrob Agents Chemother ; 45(9): 2623-7, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11502539

ABSTRACT

The efficacy of 20(S)-camptothecin (CPT), free and incorporated into sterically stabilized liposomes, has been investigated in vitro against Leishmania donovani promastigotes and in vivo in a murine model of visceral leishmaniasis. Incubation of L. donovani promastigotes with free or liposomal CPT inhibited the growth of parasites in a dose-dependent manner. Tissue distribution studies revealed that the intraperitoneal administration of liposomal CPT was efficient for the delivery of high drug levels to the liver and spleen. Treatment of infected mice with intraperitoneal injections of free and liposomal CPT significantly reduced the parasite loads in the livers by 43 and 55%, respectively, compared with the loads for untreated controls. However, both treatments caused normochromic anemia and neutropenia.


Subject(s)
Antiprotozoal Agents/therapeutic use , Camptothecin/therapeutic use , Leishmaniasis, Visceral/drug therapy , Animals , Antiprotozoal Agents/administration & dosage , Camptothecin/administration & dosage , Disease Models, Animal , Drug Carriers , Drug Delivery Systems , Drug Stability , Leishmania donovani/drug effects , Liposomes , Mice , Mice, Inbred BALB C , Treatment Outcome
10.
Sex Transm Dis ; 28(8): 484-91, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11473223

ABSTRACT

BACKGROUND: Sexually transmitted diseases (STDs) caused by HIV, herpes simplex virus (HSV), and other pathogens are spreading dramatically. The need to develop active products and vehicles to reduce this epidemic is urgent. GOAL: The efficacy of a thermoreversible gel formulation as a possible barrier to prevent the transmission of pathogens causing STDs was evaluated. STUDY DESIGN: This evaluation investigated the ability of the gel formulation to prevent infection of susceptible cells by HIV-1 and HSV-2 in vitro, the diffusion of radiolabeled herpes virus and micelles of polymer through an insertion membrane, and the electron microscopic appearance of herpes virus and gel alone or mixed together. RESULTS: The gel formulation prevents infection of susceptible cells by HIV-1 and HSV-2. It acts as an effective artificial physical barrier against the herpes virus within the first 4 hours of incubation. Herpes virus is coated by the gel or entrapped within micelles of the gel, which could hinder its attachment to target cells and inhibit its infectivity. CONCLUSION: This thermoreversible gel formulation represents an attractive matrix for the incorporation of microbicides to prevent the spread of STDs.


Subject(s)
Gels/pharmacology , HIV-1/drug effects , Herpesvirus 2, Human/drug effects , Sexually Transmitted Diseases/prevention & control , Carbon Radioisotopes , Cell Line/drug effects , HIV Infections/prevention & control , Herpes Simplex/prevention & control , Humans , Polymers/pharmacology
11.
Antimicrob Agents Chemother ; 45(8): 2229-37, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11451679

ABSTRACT

The microbicidal activity of sodium lauryl sulfate (SLS) against human immunodeficiency virus type 1 (HIV-1) was studied in cultured cells. Pretreatment of HIV-1(NL4-3) with SLS decreased, in a concentration-dependent manner, its infectivity when using 1G5 as target cells. In the absence of a viral pretreatment period or when 1G5 cells were pretreated with SLS, the surfactant-induced inactivation of viral infectivity was less pronounced, especially at concentrations between 375 and 550 microM. SLS had no effect on HIV-1 when the virus was adsorbed to 1G5 cells by a 2-h incubation period. SLS almost completely inhibited the fusion process by decreasing the attachment of HIV-1 to target cells. SLS also inhibited the infectivity of HIV-1-based luciferase reporter viruses pseudotyped with the amphotropic murine leukemia virus envelope (which enters cells in a CD4-, CCR5-, and CXCR4-independent manner), indicating that SLS may inactivate other envelope viruses. In contrast, no effect was seen with vesicular stomatitis virus envelope glycoprotein G (which enters cells through receptor-mediated endocytosis) pretreated with up to 700 microM SLS. SLS also decreased, in a dose-dependent manner, the HIV-1-dependent syncytium formation between 1G5 and J1.1 cells after a 24-h incubation. The reduction of luciferase activity was more pronounced when J1.1 cells (which express HIV-1 proteins on their surface) were pretreated with SLS rather than 1G5 cells. Taken together, our results suggest that SLS could represent a candidate of choice for use in vaginal microbicides to prevent the sexual transmission of HIV and possibly other pathogens causing sexually transmitted diseases.


Subject(s)
HIV-1/drug effects , Sodium Dodecyl Sulfate/pharmacology , Surface-Active Agents/pharmacology , Virus Replication/drug effects , Cell Membrane/physiology , Cells, Cultured , Dose-Response Relationship, Drug , Genes, Viral , HIV-1/physiology , Herpesvirus 1, Human/drug effects , Humans , Luciferases/metabolism , Sexually Transmitted Diseases/prevention & control , Viral Envelope Proteins/genetics , Virion/physiology
12.
Antimicrob Agents Chemother ; 45(6): 1671-81, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11353610

ABSTRACT

The microbicidal efficacies of two anionic surfactants, sodium lauryl sulfate (SLS) and n-lauroylsarcosine (LS), were evaluated in cultured cells and in a murine model of herpes simplex type 2 (HSV-2) intravaginal infection. In vitro studies showed that SLS and LS were potent inhibitors of the infectivity of HSV-2 strain 333. The concentrations of SLS which inhibit viral infectivity by 50% (50% inhibitory dose) and 90% (90% inhibitory dose) were 32.67 and 46.53 microM, respectively, whereas the corresponding values for LS were 141.76 and 225.30 microM. In addition, intravaginal pretreatment of mice with thermoreversible gel formulations containing 2.5% SLS or 2.5% LS prior to the inoculation of HSV-2 strain 333 completely prevented the development of genital herpetic lesions and the lethality associated with infection. Of prime interest, no infectious virus could be detected in mouse vaginal mucosa. Both formulations still provided significant protection when viral challenge was delayed until 1 h after pretreatment. Finally, intravaginal application of gel formulations containing 2.5% SLS or 2.5% LS once daily for 14 days to rabbits did not induce significant irritations to the genital mucosa, as demonstrated from macroscopic and histopathologic examinations. These results suggest that thermoreversible gel formulations containing SLS or LS could represent potent and safe topical microbicides for the prevention of HSV-2 and possibly other sexually transmitted pathogens, including human immunodeficiency virus.


Subject(s)
Anti-Infective Agents/therapeutic use , Detergents/therapeutic use , Herpes Genitalis/prevention & control , Sarcosine/analogs & derivatives , Sarcosine/therapeutic use , Sexually Transmitted Diseases/prevention & control , Sodium Dodecyl Sulfate/therapeutic use , Surface-Active Agents/therapeutic use , Administration, Topical , Analysis of Variance , Animals , Anti-Infective Agents/pharmacokinetics , Area Under Curve , Chemistry, Pharmaceutical , Chlorocebus aethiops , Detergents/pharmacokinetics , Female , Gels , Herpesvirus 2, Human , Mice , Mice, Inbred BALB C , Rabbits , Sarcosine/pharmacokinetics , Sodium Dodecyl Sulfate/pharmacokinetics , Surface-Active Agents/pharmacokinetics , Vagina/drug effects , Vagina/pathology , Vero Cells
13.
Antimicrob Agents Chemother ; 45(4): 1030-6, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11257012

ABSTRACT

The influence of sodium lauryl sulfate (SLS) on the efficacies of gel formulations of foscarnet against herpes simplex virus type 1 (HSV-1) cutaneous lesions and on the establishment and reactivation of latent virus has been evaluated in a murine model of orofacial infection. Topical treatments were given twice daily for 3 days and were initiated at 6, 24, and 48 h after virus inoculation. The gel formulation that contained both 3% foscarnet and 5% SLS and that was administered within 48 h postinfection reduced the rate of development of herpetic skin lesions. This formulation also significantly decreased the viral content in skin tissues and in ipsilateral trigeminal ganglia when it was given within 24 and 6 h postinfection, respectively. A lower level of efficacy was observed for the gel formulation containing 3% foscarnet alone. Of prime interest, the gel formulation containing 5% SLS reduced significantly the mortality rate among mice in a zosteriform model of infection. Both formulations of foscarnet had no effect on the mean titers of reactivated virus in explant cultures of ipsilateral and contralateral trigeminal ganglia from latently infected mice. The use of a gel formulation containing combinations of foscarnet and SLS could represent an attractive approach for the treatment of herpetic mucocutaneous infections.


Subject(s)
Antiviral Agents/administration & dosage , Foscarnet/administration & dosage , Herpes Simplex/prevention & control , Herpesvirus 1, Human , Sodium Dodecyl Sulfate/administration & dosage , Surface-Active Agents/administration & dosage , Administration, Topical , Animals , Drug Combinations , Gels/administration & dosage , Herpes Simplex/pathology , Herpes Simplex/virology , Herpesvirus 1, Human/isolation & purification , Herpesvirus 1, Human/physiology , Mice , Skin/pathology , Skin/virology , Survival Rate , Time Factors , Trigeminal Ganglion/virology , Virus Latency
14.
Biochim Biophys Acta ; 1468(1-2): 161-74, 2000 Sep 29.
Article in English | MEDLINE | ID: mdl-11018661

ABSTRACT

The ability of liposomes bearing anti-HLA-DR Fab' fragments at the end termini of polyethyleneglycol chains (sterically stabilized immunoliposomes) to target HLA-DR expressing cells and increase the accumulation of liposomes into lymphoid organs has been evaluated and compared to that of conventional liposomes, sterically stabilized liposomes and conventional immunoliposomes after a single subcutaneous injection to mice. The accumulation of sterically stabilized liposomes in lymph nodes was higher than that of conventional liposomes. Sterically stabilized immunoliposomes accumulated much better than conventional immunoliposomes in all tissues indicating that the presence of PEG has an important effect on the uptake of immunoliposomes by the lymphatic system. Fluorescence microscopy studies showed that sterically stabilized liposomes are mainly localized in macrophage-rich areas such as the subcapsular region of lymph nodes and in the red pulp and marginal zone of the spleen. In contrast, sterically stabilized immunoliposomes mostly accumulated in the cortex in which follicles are located and in the white pulp of the spleen. As the human HLA-DR determinant of the major histocompatibility complex class II is expressed on activated CD4+ T lymphocytes and antigen presenting cells such as monocyte/macrophages and dendritic cells, known as the cellular reservoirs of HIV-1, liposomes bearing anti-HLA-DR antibodies constitute an attractive approach to concentrate drugs in HIV-1 reservoirs and improve their therapeutic effect.


Subject(s)
Antibodies/administration & dosage , Drug Delivery Systems , HIV-1 , HLA-DR Antigens/immunology , Liposomes/immunology , Lymphoid Tissue/immunology , Animals , Antibodies/immunology , Carbocyanines/chemistry , Female , Flow Cytometry , Fluorescent Dyes , Immunoglobulin Fab Fragments/immunology , In Vitro Techniques , Liposomes/analysis , Liposomes/chemistry , Lymph Nodes/immunology , Lymphoid Tissue/drug effects , Mice , Mice, Inbred C3H , Microscopy, Fluorescence , Polyethylene Glycols/chemistry , Spleen/immunology , Tissue Distribution
15.
Antimicrob Agents Chemother ; 44(9): 2263-70, 2000 Sep.
Article in English | MEDLINE | ID: mdl-10952566

ABSTRACT

The influence of sodium lauryl sulfate (SLS) on the efficacies of topical gel formulations of foscarnet against herpes simplex virus type 1 (HSV-1) cutaneous infection has been evaluated in mice. A single application of the gel formulation containing 3% foscarnet given 24 h postinfection exerted only a modest effect on the development of herpetic skin lesions. Of prime interest, the addition of 5% SLS to this gel formulation markedly reduced the mean lesion score. The improved efficacy of the foscarnet formulation containing SLS could be attributed to an increased penetration of the antiviral agent into the epidermis. In vitro, SLS decreased in a concentration-dependent manner the infectivities of herpesviruses for Vero cells. SLS also inhibited the HSV-1 strain F-induced cytopathic effect. Combinations of foscarnet and SLS resulted in subsynergistic to subantagonistic effects, depending on the concentration used. Foscarnet in phosphate-buffered saline decreased in a dose-dependent manner the viability of cultured human skin fibroblasts. This toxic effect was markedly decreased when foscarnet was incorporated into the polymer matrix. The presence of SLS in the gel formulations did not alter the viabilities of these cells. The use of gel formulations containing foscarnet and SLS could represent an attractive approach to the treatment of herpetic mucocutaneous lesions, especially those caused by acyclovir-resistant strains.


Subject(s)
Antiviral Agents/therapeutic use , Foscarnet/therapeutic use , Herpes Simplex/drug therapy , Skin Diseases, Viral/drug therapy , Sodium Dodecyl Sulfate/therapeutic use , Administration, Topical , Animals , Antiviral Agents/pharmacokinetics , Cell Survival/drug effects , Chemistry, Pharmaceutical , Chlorocebus aethiops , Disease Models, Animal , Drug Synergism , Female , Foscarnet/pharmacokinetics , Foscarnet/toxicity , Herpes Simplex/metabolism , Herpesvirus 1, Human/drug effects , Humans , Mice , Mice, Hairless , Skin Absorption/drug effects , Skin Diseases, Viral/metabolism , Sodium Dodecyl Sulfate/pharmacokinetics , Sodium Dodecyl Sulfate/toxicity , Surface-Active Agents/pharmacology , Vero Cells
16.
AIDS ; 14(16): 2457-65, 2000 Nov 10.
Article in English | MEDLINE | ID: mdl-11101055

ABSTRACT

OBJECTIVE: To evaluate the ability of liposomes bearing anti-HLA-DR Fab' fragments (immunoliposomes) and containing amphotericin B (AmB) to target and neutralize cell-free HIV-1 particles and virally-infected cells. METHODS: The effect of AmB on the attachment and fusion of HIV-1(NL4-3) to Jurkat E6.1 cells has been evaluated using a p24 enzymatic assay. The ability of AmB to inhibit HIV-1-based luciferase reporter viruses pseudotyped with HXB2, AML-V and VSV-G envelopes has been evaluated in Jurkat E6.1 cells. The efficacy of free and immunoliposomal AmB to inhibit cell-free HIV, that have incorporated or not HLA-DR molecules, has been evaluated in HLA-DR/negative (NEG) 1G5 T cells and HLA-DR/positive (POS) Mono Mac 1 cells. RESULTS: AmB inhibited HIV infectivity independently of the nature of viral envelope proteins. Pretreatment of HIV with AmB had no major effect on viral attachment and fusion process to Jurkat E6.1 cells. Immunoliposomal AmB (0.5 microg/ml) led to a 77% inhibition of replication of HLA-DR/POS HIV-1 with no cell toxicity, whereas free AmB had no significant antiviral activity at this concentration. A complete inhibition of viral replication was observed following incubation of viruses with immunoliposomal AmB (2.5 microg/ml). Anti-HLA-DR immunoliposomes containing AmB had no effect on the infectivity of HLA-DR/NEG HIV-1 particles in HLA-DR/NEG T lymphoid cells but completely inhibited replication of viruses in an HLA-DR/POS monocytic cell line. CONCLUSION: The incorporation of neutralizing agents in anti-HLA-DR immunoliposomes could represent a novel therapeutic strategy to specifically target cell-free HIV particles and virally-infected cells to treat HIV infection more efficiently.


Subject(s)
Amphotericin B/pharmacology , Antibodies/immunology , HIV Infections/virology , HIV-1/drug effects , HLA-DR Antigens/immunology , Liposomes/immunology , Antibodies/pharmacology , Antibody Specificity , Cell Line , Drug Delivery Systems , HIV-1/immunology , HIV-1/pathogenicity , Humans , Immunoglobulin Fab Fragments/immunology , Jurkat Cells , Liposomes/administration & dosage
17.
J Clin Microbiol ; 38(1): 110-9, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10618073

ABSTRACT

The efficacy of sodium lauryl sulfate (SLS), a sulfated anionic chaotropic surfactant, and dextran sulfate (DS), a polysulfated carbohydrate, against herpes simplex virus (HSV) and human immunodeficiency virus (HIV) infections was evaluated in cultured cells and in different murine models of HSV infection. Results showed that both SLS and DS were potent inhibitors of the infectivities of various HSV-1 and HSV-2 strains. Pretreatment of HIV-1 (strain NL4-3) with SLS also reduced its infectivity to 1G5 cells. DS prevented the binding of HSV to cell surface receptors and therefore its entry into cells. Pretreatment of HSV-1 (strain F) with 50 microM SLS resulted in a complete loss of virus infectivity to Vero cells. However, viruses were able to enter into cells and to produce in the nuclei capsid shells devoid of a DNA core. The amount of the glycoprotein D gene produced in these cells remained unchanged compared to controls, suggesting that SLS could interfere with the maturation of the virus. At a higher SLS concentration (100 microM), HSV was highly damaged by SLS pretreatment and only a few viral particles could enter into cells to produce abnormal capsids. Although DS was a more potent inhibitor of HSV infectivity in vitro, it was unable to provide any protection in murine models of HSV infection. However, SLS conferred a complete protection of animals infected cutaneously with pretreated viruses. In addition, skin pretreatment of mice with a polymer formulation containing SLS completely prevented the development of cutaneous lesions. More interestingly, intravaginal pretreatment of mice with SLS in a buffered solution also completely protected against lethal HSV-2 infection. Taken together, our results suggest that SLS could thus represent a candidate of choice as a microbicide to prevent the sexual transmission of HIV, HSV, and possibly other pathogens that cause sexually transmitted diseases.


Subject(s)
Antiviral Agents/pharmacology , Dextran Sulfate/pharmacology , HIV-1/drug effects , Simplexvirus/drug effects , Sodium Dodecyl Sulfate/pharmacology , Animals , Chlorocebus aethiops , Dose-Response Relationship, Drug , Female , Genes, Viral , Herpesvirus 1, Human/drug effects , Herpesvirus 2, Human/drug effects , Mice , Mice, Hairless , Sexually Transmitted Diseases/prevention & control , Vaginal Diseases/virology , Vero Cells , Viral Envelope Proteins/genetics , Viral Plaque Assay , Virus Replication/drug effects
18.
Antimicrob Agents Chemother ; 44(1): 30-8, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10602719

ABSTRACT

The topical efficacies of foscarnet and acyclovir incorporated into a polyoxypropylene-polyoxyethylene polymer were evaluated and compared to that of 5% acyclovir ointment (Zovirax) by use of a murine model of cutaneous herpes simplex virus type 1 infection. All three treatments given three times daily for 4 days and initiated 24 h after infection prevented the development of the zosteriform rash in mice. The acyclovir formulation and the acyclovir ointment reduced the virus titers below detectable levels in skin samples from the majority of mice, whereas the foscarnet formulation has less of an antiviral effect. Reducing the number of treatments to a single application given 24 h postinfection resulted in a significantly higher efficacy of the formulation of acyclovir than of the acyclovir ointment. Acyclovir incorporated within the polymer was also significantly more effective than the acyclovir ointment when treatment was initiated on day 5 postinfection. The higher efficacy of the acyclovir formulation than of the acyclovir ointment is attributed to the semiviscous character of the polymer, which allows better penetration of the drug into the skin.


Subject(s)
Acyclovir/administration & dosage , Foscarnet/administration & dosage , Herpes Simplex/drug therapy , Skin Diseases, Viral/drug therapy , Acyclovir/pharmacokinetics , Administration, Topical , Animals , Drug Administration Schedule , Female , Foscarnet/pharmacokinetics , Mice , Mice, Hairless , Ointments , Pharmaceutical Vehicles , Polymers/administration & dosage , Time Factors
19.
J Ocul Pharmacol Ther ; 15(5): 465-77, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10530708

ABSTRACT

The efficacy of intravitreal foscarnet injections was evaluated in a rabbit model of Herpes simplex virus type-1 (HSV-1) retinitis. In untreated infected animals, viral titration revealed that the optic chiasm, vitreous and chorioretina were positive for HSV-1. On the other hand, foscarnet treatment significantly decreased the viral count in the chorioretina when compared to the untreated group. Immunolocalization of HSV in untreated infected animals clearly showed infected cells in the outer and inner layers of the retina and also in the ciliary body of the eye. Clinical examination by indirect ophthalmoscopy indicated an absence of optic nerve congestion and a lower level of vitritis in foscarnet treated animals compared to the untreated group. It is concluded that intravitreal injections of foscarnet reduced the viral titer in the chorioretina in a rabbit model of HSV-1 retinitis. This route of administration might be valuable for the treatment of CMV retinitis in AIDS patients with sight threatening lesions or intolerance to intravenous anti-CMV drugs.


Subject(s)
Choroid/virology , Foscarnet/therapeutic use , Herpes Simplex/drug therapy , Herpesvirus 1, Human/drug effects , Retina/virology , Retinitis/drug therapy , Administration, Topical , Animals , Choroid/drug effects , Herpes Simplex/pathology , Ophthalmoscopy , Optic Nerve/pathology , Optic Nerve/virology , Rabbits , Retina/drug effects , Retinitis/pathology , Retinitis/virology
20.
Biochim Biophys Acta ; 1421(2): 284-94, 1999 Oct 15.
Article in English | MEDLINE | ID: mdl-10518698

ABSTRACT

The ability of liposomes bearing anti-HLA-DR Fab' fragments to target cells expressing the human HLA-DR determinant of the major histocompatibility complex class II (MHC-II) has been evaluated and compared to that of conventional liposomes. Anti-HLA-DR immunoliposomes did not bind to HLA-DR-negative cells. In contrast, a high level of binding was observed following incubation of immunoliposomes with cells bearing important levels of human HLA-DR. The accumulation of conventional and murine anti-HLA-DR immunoliposomes in different tissues has been investigated following a single subcutaneous injection given in the upper back of C3H mice. Anti-HLA-DR immunoliposomes resulted in a much better accumulation in the cervical and brachial lymph nodes when compared to conventional liposomes. The accumulation in the liver was similar for both liposomal preparations, whereas an approximately twofold decrease in accumulation was observed for immunoliposomes in the spleen. Given that HLA-DR surface marker is expressed on monocyte/macrophages and activated CD4+ T lymphocytes, the primary cellular reservoirs of the human immunodeficiency virus (HIV), the use of liposomes bearing surface-attached anti-HLA-DR could constitute a convenient strategy to more efficiently treat this debilitating retroviral disease. Moreover, the reported incorporation of high amounts of host-encoded HLA-DR proteins by HIV particles renders the use of liposomes bearing anti-HLA-DR antibodies even more attractive.


Subject(s)
HLA-DR Antigens/immunology , Immunoglobulin Fab Fragments/pharmacology , Lymph Nodes/drug effects , Animals , Drug Carriers , Female , Humans , Liposomes , Lymph Nodes/immunology , Mice , Mice, Inbred C3H , Phosphatidylethanolamines
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