On the homology of banding patterns in segment long spacing (SLS) aggregates of collagen from various tissues--a systematic study.
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Animals↗
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Calcium antagonists in sodium lactobionate sucrose solution for rat liver preservation.
The effects of the calcium antagonists, chlorpromazine (CPZ), nisoldipine (NIS), trifluoperazine (TFP), and nicardipine (NIC) were compared in rat livers following either 20- or 30-hr ice storage in sodium lactobionate sucrose solution (SLS). Survivals beyond 7 days after orthotopic liver transplantation following 20-hr cold storage were 1/14 in the University of Wisconsin solution, 4/14 in SLS, 4/8 in UW+CPZ, 7/8 in SLS+CPZ. Survivals beyond 7 days after OLT following 30-hr cold storage were 3/8 in SLS+CPZ, 3/8 in SLS+NIS, 2/8 in SLS+TFP, 0/8 in SLS+NIC, and 0/8 in SLS alone. Survival rates were significantly (P less than 0.05) better in both SLS+CPZ and SLS+NIS than in UW and SLS alone. The effluent lactate dehydrogenase (LDH) levels and pH changes were measured at the time of OLT. After 20 hr, LDH levels were 525 +/- 78 IU/L (mean +/- SEM) in UW, 492 +/- 44 in SLS, 322 +/- 35 in UW+CPZ, and 290 +/- 39 in SLS+CPZ. After 30 hr, LDH values were 416 +/- 40 in SLS+CPZ, 450 +/- 25 in SLS+NIS, 448 +/- 21 in SLS+TFP, 573 +/- 18 in SLS+NIC, and 614 +/- 68 in SLS. The LDH levels for SLS+CPZ and SLS+NIS were significantly lower than those of SLS and UW (P less than 0.01). The pH changes in the effluent were significantly less in both the CPZ and NIS groups (P less than 0.01). This study demonstrated improved liver preservation by the use of a simplified colloid-free lactobionate solution containing sodium as the principal cation. The addition of CPZ or NIS to the solution demonstrated the same potency for significant improvement in efficacy of this solution, while NIC was ineffective.
Adenosine↗
Biophysical alteration of lung surfactant by extracts of cotton dust.
Byssinosis, a lung disease that can affect cotton mill workers, may be caused in part by lipopolysaccharides (LPS) from Gram negative bacteria. In vitro, LPS complexes with sheep lung surfactant (SLS). To determine whether LPS in extracts of cotton dust alters the biophysical characteristics of lung surfactant, aqueous extracts (1.0% w:v) of sterile surgical cotton (SSC) and a bulk raw cotton dust (1182DB) were prepared. Aliquots of the soluble extracts were incubated with SLS and studied by sucrose gradient centrifugation, surface tension analysis, and high pressure liquid chromatography (HPLC). The chromatography was employed to analyse for 3-hydroxymyristate (3-HM), a fatty acid indicating LPS. Also, purified Enterobacter agglomerans LPS and 3-HM as controls and as mixtures with SLS, were studied by HPLC. Sucrose gradient centrifugation showed that SLS-SSC, SLS-1182DB, and the SLS control had similar densities that differed from the remaining controls. The SLS-1182DB exhibited a floccule absent in the other samples. Surface tension values of SLS-SSC and SLS-1182DB differed significantly from all controls but only slightly from one another. 3-Hydroxymyristate was detected by HPLC in the 3-HM control, EA-LPS, SLS-EA-LPS, and SLS-1182DB, but not in SLS-SSC or the remaining controls. Apparently, 3-HM was below the HPLC detection range in SSC. The data indicate that LPS in the 1182DB, SSC and EA-LPS samples complexed with SLS. Floccule development in SLS-1182DB but not in SLS-EA-LPS suggests a further component(s) present in the bulk raw cotton dust, as well as LPS, which complexes with SLS. The data suggest that biophysical alterations to lung surfactant may play a part in the pathogenesis of byssinosis.
Animals↗
Quantification of sodium lauryl sulfate penetration into the skin and underlying tissue after topical application--pharmacological and toxicological implications.
Sodium lauryl sulfate (SLS) is known to penetrate skin and cause cutaneous irritation. Some of these effects have been well-defined using bioengineering techniques. In this study, the ability of SLS to penetrate skin was quantified in a hairless rat model. In addition, local deep tissue penetration and systemic exposure to SLS were also evaluated to assess the toxic potential of topically applied SLS. SLS was observed to penetrate directly to a depth of about 5-6 mm below the applied site. Systemic redistribution was predominantly responsible in determining concentrations of SLS in tissues deeper than 5-6 mm. Epidermal concentrations of SLS after application of 1% (34 mM) aqueous SLS solution for 24 h were above the threshold levels which are known to evoke typical skin irritation responses. Deeper underlying tissues including dermis, subcutaneous, and muscle may also be exposed to high levels of SLS. Topically applied SLS was also observed in blood and contralateral tissues but the observed levels were not likely to elicit any systemic side effects at these doses. Traces of SLS were observed in tissues 7 days after single 24 h application of SLS, which supports the prolonged barrier disruption data generated using conventional bioengineering techniques. Cumulative treatment of SLS significantly increased the concentration of this compound in the underlying epidermis. The known preferential affinity of SLS for skin lipids and proteins was further confirmed by both in vitro and in vivo results. However, in vitro studies failed to predict the underlying tissue toxicity of SLS under the patch site when compared to the in vivo results. Such quantitative pharmacokinetic-pharmacodynamic correlations may be useful predictors for effective use of surfactants as penetration enhancers in cosmetic, pharmaceutical, and industrial applications.
Administration, Topical↗
Clearance of sodium lauryl sulphate from the oral cavity.
Sodium lauryl sulphate (SLS) is used in toothpaste and mouth rinses as an emulsifying and surface cleaning agent. SLS has been implicated in an increased incidence of oral irritation in subjects predisposed to recurrent aphthous stomatitis (RAU). Hence, the purpose of this study was to determine the levels of SLS found in the oral cavity following rinsing with an SLS containing mouth rinse and brushing with a SLS containing dentifrice. An analytical method to separate SLS from saliva and other complex systems was developed. The method used high performance liquid chromatography (HPLC) and detection performed using conductivity measurements. Standard curves with known concentrations showed a detection limit of less than 0.4 ug SLS/ml of fluid. 2 clinical studies were conducted to determine the amount of SLS retained in the mouth by a healthy population after rinsing or brushing with commercially available products. The results showed, after rinsing, that 96% of the available SLS from the rinse was recovered in the collected samples within 2 min. Similarly, after brushing, 86% of the SLS contained within the toothpaste was recovered from the collected samples within the first 10 min. These results showed that the amount of SLS retained in the oral cavity was minimal and the contact time between SLS and the oral cavity was very short. A 2nd study was conducted to measure the amount of SLS retained in the mouth by a population susceptible to RAU. After rinsing, 97% of the available SLS was recovered within the first 2 min. Following brushing, 89% of the SLS in the dentifrice was recovered within the first 10 min. These results were comparable to those determined by the study involving the healthy population.
Adult↗
An improved MLC segmentation algorithm and software for step-and-shoot IMRT delivery without tongue-and-groove error.
We present an improved multileaf collimator (MLC) segmentation algorithm, denoted by SLS(NOTG) (static leaf sequencing with no tongue-and-groove error), for step-and-shoot intensity-modulated radiation therapy (IMRT) delivery. SLS(NOTG) is an improvement over the MLC segmentation algorithm called SLS that was developed by Luan et al. [Med. Phys. 31(4), 695-707 (2004)], which did not consider tongue-and-groove error corrections. The aims of SLS(NOTG) are (1) shortening the treatment times of IMRT plans by minimizing their numbers of segments and (2) minimizing the tongue-and-groove errors of the computed IMRT plans. The input to SLS(NOTG) is intensity maps (IMs) produced by current planning systems, and its output is (modified) optimized leaf sequences without tongue-and-groove error. Like the previous SLS algorithm [Luan et al., Med. Phys. 31(4), 695-707 (2004)], SLS(NOTG) is also based on graph algorithmic techniques in computer science. It models the MLC segmentation problem as a weighted minimum-cost path problem, where the weight of the path is the number of segments and the cost of the path is the amount of tongue-and-groove error. Our comparisons of SLS(NOTG) with CORVUS indicated that for the same intensity maps, the numbers of segments computed by SLS(NOTG) are up to 50% less than those by CORVUS 5.0 on the Elekta LINAC system. Our clinical verifications have shown that the dose distributions of the SLS(NOTG) plans do not have tongue-and-groove error and match those of the corresponding CORVUS plans, thus confirming the correctness of SLS(NOTG). Comparing with existing segmentation methods, SLS(NOTG) also has two additional advantages: (1) SLS(NOTG) can compute leaf sequences whose tongue-and-groove error is minimized subject to a constraint on the maximum allowed number of segments, which may be desirable in clinical situations where a treatment with the complete correction of tongue-and-groove error takes too much time, and (2) SLS(NOTG) can be used to minimize a more general type of error called the tongue-or-groove error.
Algorithms↗
Successful 20-hour rat liver preservation with chlorpromazine in sodium lactobionate sucrose solution.
We investigated the effect of the addition of chlorpromazine to a new, simplified organ preservation solution, sodium lactobionate sucrose (SLS), for 20-hour hypothermic rat liver preservation. Survival beyond 7 days after orthotopic transplantation of the stored liver was eight of eight rats in control groups (immediate transplantation, less than 1-hour preservation), one of 14 rats with the University of Wisconsin (UW) solution, four of 14 rats with SLS, seven of eight rats with SLS + chlorpromazine, 1 mg/L, and seven of eight rats with SLS + chlorpromazine, 10 mg/L. The differences is survival between UW and SLS and between SLS and SLS + chlorpromazine were significant (p less than 0.05). Lactic dehydrogenase levels in the effluent after reflushing through the portal vein at the time of transplantation were 145 +/- 20 IU/L (mean +/- SEM) in the controls, 525 +/- 78 IU/L in UW, 492 +/- 44 IU/L in SLS, 290 +/- 39 IU/L in SLS + chlorpromazine, 1 mg/L, 290 +/- 11 IU/L in SLS + chlorpromazine, 10 mg/L. The values for the SLS + chlorpromazine were significantly lower than for SLS and UW (p less than 0.05). The pH of the effluent was 7.10 +/- 0.10 in controls, 6.42 +/- 0.12 in UW, 6.64 +/- 0.18 in SLS, and 7.07 +/- 0.02 in SLS + chlorpromazine, 1 mg/L and 10 mg/L. The pH drop was significantly greater in the groups without chlorpromazine (p less than 0.01). This study shows that superior rat liver preservation was achieved with a simplified lactobionate solution containing sodium as the principal cation, sucrose in place of raffinose, and omitting the colloid and several of the other UW components. The addition of low concentrations of chlorpromazine further enhanced the effectiveness of this solution, without the need for donor pretreatment.
Adenosine↗
Carrier detection for Sjögren-Larsson syndrome.
Sjögren-Larsson syndrome (SLS) is an autosomal recessive disorder associated with reduced activity of the fatty alcohol: NAD+ oxidoreductase complex (FAO). Recent studies indicate that SLS patients are specifically deficient in the fatty aldehyde dehydrogenase (FALDH) component of FAO. To investigate the possibility of carrier detection for SLS, FAO and FALDH activities were measured in cultured skin fibroblasts from normal controls, obligate SLS heterozygotes, and SLS homozygotes using the 18-carbon substrates octadecanol and octadecanal. Three of 11 heterozygotes for SLS had FAO activities that were within the normal range; the other 8 SLS heterozygotes had FAO activities below normal. In contrast, fibroblast FALDH activity was more effective than FAO in discriminating SLS heterozygotes from normal controls. FALDH activity (nmol min-1 (mg protein)-1) in normal controls was 8.54 +/- 1.16 (mean +/- SD; range 6.95-10.77; n = 12) and in SLS heterozygotes was 5.12 +/- 1.31 (range 3.28-6.96; n = 11), or 60 +/- 15% of mean normal activity. One SLS heterozygote had an FALDH activity within the lower range of normal; this heterozygote had an FAO activity below normal. None of the SLS heterozygotes had an FAO or FALDH activity that was in the range of that measured in SLS homozygotes. These results indicate that measurement of FAO and FALDH activities in cultured skin fibroblasts using 18-carbon substrates is useful for SLS carrier detection.
Alcohol Oxidoreductases↗
Anti-cancer potential of sesquiterpene lactones: bioactivity and molecular mechanisms.
Sesquiterpene lactones (SLs) are the active constituents of a variety of medicinal plants used in traditional medicine for the treatment of inflammatory diseases. In recent years, the anti-cancer property of various SLs has attracted a great deal of interest and extensive research work has been carried out to characterize the anti-cancer activity, the molecular mechanisms, and the potential chemopreventive and chemotherapeutic application of SLs. In this review, we attempt to summarize the current knowledge of the anti-cancer properties of SLs by focusing on the following important issues. First, we discuss the structure-activity relationship of SLs. All SLs contain a common functional structure, an alpha-methylene-gamma-lactone group, and this important chemical characteristic means that the thiol-reactivity of SLs is an underlying mechanism responsible for their bioactivities. Second, we assess the experimental evidence for the anti-cancer function of SLs obtained from both in vitro cell culture and in vivo animal models. Various SLs have been demonstrated to execute their anti-cancer capability via inhibition of inflammatory responses, prevention of metastasis and induction of apoptosis. Thirdly, we outline the molecular mechanisms involved in the anti-cancer activity of SLs, in particular, the SL-thiols reaction, the effect of SLs on cell signaling pathways such as nuclear transcription factor-kappaB (NF-kappaB) and mitogen-activated protein kinases (MAPK). Finally, we recapitulate some important SLs with regards to their anti-cancer activities and their potential in anti-cancer drug development. Taken together, many SLs are emerging as promising anti-cancer agents with potential applications in both cancer chemotherapy and chemoprevention.
Animals↗
Radiographic detection of single strut leg separations as a putative basis for prophylactic explantation of Björk-Shiley convexo-concave heart valves.
Cineradiography, using higher kVp and two or more specified profiles for each outlet strut leg, was used to evaluate Björk-Shiley convexo-concave (C/C) heart valves with epidemiologically defined > 0.1% per year estimated fracture rates. Among 828 mitral valves, eight radiographs were assessed as definite single leg separations (SLS) and 23 were read as probable SLS. Explantation confirmed SLS in 24 valves; 4 probables were false positives, and 3 patients with probable SLS ratings decided against explantation. Four patients with SLS died, an operative mortality of 14%. Only 23 mitral and 6 aortic valves receiving ratings ranging from apparently normal to suspicious have become available for verification; 1 rated apparently normal was found to have a SLS. Two patients experienced fatal fractures and 1 SLS valve was explanted 3 to 15 months after apparently normal x-ray studies; it cannot be known if a SLS was or was not present at the time of these examinations. As 97% of negatively rated valves remain in situ, the sensitivity of the test is similarly not known. Only 1 SLS has been detected among 136 aortic valves. Uncertainty about test accuracy and SLS progression condition the clinical utility of radiographic SLS detection, particularly with respect to assurance from apparently normal readings. However, radiographic identification of an SLS substantially enhances epidemiologically derived risk categorization as a basis for consideration of prophylactic replacement for the approximately 12,000 valves with a > 0.1% estimated annual fracture risk, currently thought to be implanted in living patients.
Aortic Valve↗
Purification of lactonic sophorolipids by crystallization.
Various experimental methods for purifying lactonic sophorolipids (SLs) via crystallization were studied. The commonly used solvent, ethanol, was found to have much higher solubility of the lactonic SLs than the acid SLs. Consequently, for purification of lactonic SLs, ethanol not only lacked the selectivity in removing acidic SLs but also resulted in significant loss of desired products. Aqueous buffers were subsequently studied as the solvent, based on the rationale that acidic SLs, having the free carboxylic acid group(s), are more hydrophilic than the lactonic SLs, especially at higher pH. Both phthalate and phosphate buffers were found more suitable for purifying lactonic SLs than ethanol. A practical and effective method for purifying lactonic SLs to about 99% purity using phosphate buffers was developed. The FTIR spectra also showed significantly less SL components with free acid groups in the purified SLs than in the crude SLs, confirming the removal of acidic SLs in the purification.
Buffers↗
Dissolution media for in vitro testing of water-insoluble drugs: effect of surfactant purity and electrolyte on in vitro dissolution of carbamazepine in aqueous solutions of sodium lauryl sulfate.
The intrinsic dissolution rate and solubility of carbamazepine was measured in aqueous solutions of sodium lauryl sulfate (SLS) prepared with two different grades of purity, 95 and 99%, and 95% SLS in 0.15 M NaCl to determine the effect of surface-active impurities and electrolytes. Four significant observations resulted from this work: (1) the equilibrium coefficients calculated from the solubility experiments in the 99% SLS, 95% SLS, and 95% with 0.15 M NaCl SLS solutions were 295, 265, and 233 L/mol, respectively; (2) the dissolution rate enhancement in the 99% SLS was 10% greater than that in the 95% SLS and 95% with 0.15 M NaCl solutions, which were not significantly different; (3) the diffusion coefficients of the drug-loaded micelles estimated from the dissolution experiments were 8.4 x 10(-7) cm2/s for the 99% SLS, 9.5 x 10(-7) cm2/s for the 95% SLS, and 1.2 x 10(-6) cm2/s for the 95% with 0.15 M NaCl; and (4) the critical micelle concentrations for the 99% SLS, 95% SLS, and 95% SLS with 0.15M NaCl were 6.8, 4.2, and 0.35 mM, respectively. The results of this study clearly illustrate the sensitivity of the micelle to impurities and electrolytes with regard to size and loading capacity and the effect these changes have on the solubility and dissolution rate. Therefore, when using surfactants in dissolution media for in vitro testing of dosage forms, consideration must be given to the level of impurities present so that the results are consistent and reliable. Intrinsic dissolution rate, surface tension, or solubility measurements may be useful, convenient methods for identifying changes in the surfactant due to either degradation or lot-to-lot variability.
Carbamazepine↗
Simultaneous sodium lauryl sulphate testing improves the diagnostic validity of allergic patch tests. Results from a prospective multicentre study of the German Contact Dermatitis Research Group (Deutsche Kontaktallergie-Gruppe, DKG).
BACKGROUND: There is evidence that a higher skin susceptibility may induce nonspecific erythematous or weak positive reactions to contact allergens in patch testing. OBJECTIVES: To evaluate whether simultaneous application of sodium lauryl sulphate (SLS) along with diagnostic patch tests with contact allergens can provide information regarding skin irritability which may help to discriminate allergic from nonspecific irritant reactions to contact allergens. METHODS: Between July 2001 and June 2003, this prospective study collected patch test data of 5971 patients from 19 centres in Germany and Austria in the Information Network of Departments of Dermatology (IVDK). In addition to contact allergens (standard series and eight known 'problematic' allergens with a low reaction index and a high positivity ratio: 1,3-diphenylguanidine, amerchol L-101, benzalkonium chloride, benzoyl peroxide, cocamidopropyl betaine, octyl gallate, phenyl mercuric acetate and propylene glycol), patches with SLS 0.5% and 0.25% aq. were applied. Reactions to the allergens and to SLS were analysed at the IVDK data centre. The association between an erythematous or positive reaction to a certain allergen and an irritant reaction to SLS was assessed with logistic regression analysis, at the same time controlling for the influence of age and sex. RESULTS: Of the 29 allergens of the standard series, 23 and 21 gave a higher percentage of nonspecific erythematous reactions in patients with an irritant reaction to 0.25% and 0.5% SLS, respectively, in comparison with SLS-negative patients. All eight 'problematic' allergens gave an increased percentage of nonspecific erythematous reactions. Similarly, 22 and 21 allergens of the standard series gave a higher percentage of positive allergic reactions in patients with an irritant reaction to 0.25% and 0.5% SLS, respectively, and seven of the eight 'problematic' allergens gave a higher percentage of positive allergic reactions (exception: octyl gallate). For most allergens, the markers of skin reaction (reaction index and positivity ratio) were worse in SLS-positive patients. Differences were more pronounced when testing with SLS 0.25% than with SLS 0.5%. CONCLUSIONS: Because there is a convincing association between skin irritability (evaluated by SLS test) and the degree of skin reaction to contact allergens, the SLS test may help in deciding whether a doubtful erythematous or weakly 'positive' skin reaction should be interpreted as allergic or irritant.
Adult↗
Relationship of cellular potential hemolysin in group A streptococci to extracellular streptolysin S.
The relationship of streptolysin S (SLS) and a cellular potential hemolysin (PH) activatable by sonication was examined in strain C203S (a known high producer of SLS), its SLS(-) mutant (C203U), and in 20 other group A streptococci of various M and T serotypes. All strains shown to form SLS (ribobycleic acid (RNA)-core SLS) contained PH. The two strains lacking PH were the only ones that did not produce SLS In strain C203S, formation of SLS bycells incubated with RNA-core for 60 min at 47 C in a nongrowth basal medium (Bernheimer's basal medium) was followed by a marked decrease (99.6% loss) of PH titer. Without stimulation of SLS production by addition of RNA-sore, the same incubation resulted in a progressive but less marked fall (38.8%loss in 60 min) of PH titer: these cells produced disproportionately low titers of SLS on subsequent addition of RNA-core. This effect of prior incubation in Bernheimer's basal medium on SLS titer was partially nullified by use of fresh medium after 30 min, but not after 60 min, and did not occur during 60 min of incubation at OC. These results provide additional evidence for a precursor-product relationship between PH and SLS. They also suggest that a medium factor (or factors) is utilized or destroyed at 37 C and that this factor is essential to both the stability of PH and its efficient conversion to SLS.
Hemolysin Proteins↗
Reaggregation behavior of different types of collagen in vitro: variations in the occurrence and structure of dimeric segment long-spacing collagen.
Segment long-spacing collagen (SLS) can be precipitated from solutions of collagen using ATP as the inducing agent. Dimeric SLS aggregates have been observed in addition to monomeric SLS. We have compared collagen types I, II, III, and V with respect to their ability to form dimeric SLS in vitro. These collagen types were isolated from bovine tissues and characterized by polyacrylamide slab gel electrophoresis of the respective alpha-chains. Only monomeric SLS can be detected in preparations of collagen types I and III. Dimeric SLS, on the other hand, accounts for the majority of the crystallites seen in preparations of collagen types II and V. Dimeric SLS from both collagen types II and V reveal overlap zones at the carboxy-terminal ends of the collagen molecules. However, dimeric SLS from collagen types II and V differ with respect to their overlap distances. Significant portions of the triple helical domains of collagen molecules are occupied by the overlap region of dimeric SLS from type II collagen. On the other hand, dimeric SLS from type V collagen is composed of molecules overlapping only at their short nonhelical telopeptides. It is concluded that the ability of collagen molecules to aggregate into dimeric SLS under defined experimental conditions is collagen type dependent.
Adenosine Triphosphate↗
Variation in barrier impairment and inflammation of human skin as determined by sodium lauryl sulphate penetration rate.
BACKGROUND: Skin irritability after a brief exposure to the model skin irritant, sodium lauryl sulphate (SLS), is known to vary considerably between individuals. A difference in the skin barrier to SLS may contribute to this variation. To date, no human in vivo data have been available on SLS penetration into the skin. OBJECTIVES: We studied whether the SLS penetration rate into the stratum corneum (SC) is related to impairment of the water barrier function and inflammation of the skin. METHODS: The penetration of SLS into the SC was assessed using a noninvasive tape-stripping procedure in 20 volunteers after a 4-h exposure to 1% SLS. Additionally, the effect of a 24-h exposure to 1% SLS on the skin water barrier function was assessed by measuring the transepidermal water loss (TEWL). The accompanying inflammation was quantified by measuring erythema. RESULTS: The mean +/- SD diffusivity of SLS (D) and the SLS permeability coefficient (Kp) were 1.4 +/- 0.6 x 10(-8) cm2 h(-1) and 1.5 +/- 0.7 x 10(-3) cm h(-1), respectively. A multiple regression analysis showed that the baseline TEWL, SC thickness and SLS penetration parameters K (SC/water partition coefficient) and D clearly influenced the increase in TEWL after the 24-h irritation test (explained variance: r2 = 0.80). Change in erythema was mainly influenced by SC thickness. CONCLUSIONS: We found that variation in the barrier impairment and inflammation of human skin depends on the SLS penetration rate, which was mainly determined by SC thickness.
Adolescent↗
Sodium lauryl sulfate abrogates human immunodeficiency virus infectivity by affecting viral attachment.
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.
Cell Membrane↗
In vitro and in vivo evaluations of sodium lauryl sulfate and dextran sulfate as microbicides against herpes simplex and human immunodeficiency viruses.
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.
Animals↗