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Biomedical subjects

S Shapiro

Publications and source records attributed to S Shapiro.

At least 19 recordsLinked to original sources
PubMed2006

Does retention of the ovaries improve long-term survival after hysterectomy? The validity of the epidemiological evidence.

Based on a decision analysis of multiple epidemiological studies, it has been claimed that, among women hysterectomized for benign disease, removal of the ovaries before the age of 65 years decreases long-term survival, and that the benefit conferred by retaining the ovaries outweighs any reduction in ovarian cancer mortality among oophorectomized women who are at average risk of ovarian cancer. The decision analysis failed to allow for the inevitable complexity involved in an overarching quantitative analysis of multiple outcomes, and to do so would not have been feasible; it made multiple assumptions, some of which could not be defended; a definition of 'average risk' of ovarian cancer was not provided, and the validity of the concept of 'average risk' was not considered; sensitivity analyses designed to test the robustness of the data were inadequate. The findings from decision analysis cannot be used as evidence to determine whether bilateral oophorectomy poses a public health problem in terms of long-term survival.

Adult↗
PubMed2006

Risk of cardiovascular disease in relation to the use of combined postmenopausal hormone therapy: detection bias and resolution of discrepant findings in two Women's Health Initiative studies.

CONTEXT: In a recent analysis of data in the Women's Health Initiative (WHI) clinical trial and observational studies, the overall risks of coronary heart disease, stroke and venous thromboembolism, in postmenopausal women who used combined therapy with conjugated estrogens and medroxyprogesterone acetate, were lower in the observational data. However, the risks became more similar within similar duration categories of follow-up. In both studies, there was initial elevation, followed by a duration-dependent reduction, in the risks. The investigators suggest that the discrepancies in the overall risks may be due to weighting by short-duration exposure in the clinical trial, and long-duration exposure in the observational study. CRITIQUE: In the clinical trial, 44% of the hormone therapy recipients were unblinded, mainly because of persistent vaginal bleeding, and awareness of exposure status was therefore common; in the observational study, all exposed women were aware. When follow-up in the WHI studies commenced, extensive publicity was given to evidence to suggest that, among women who had already sustained a myocardial infarction, combined hormone therapy may not decrease the risk of a second myocardial infarct, as hypothesized, but instead increase it. From the commencement of follow-up onward, detection bias was therefore possible in both WHI studies. That possibility was further reinforced after about 3 years of follow-up, and again a year later, when the clinical trial participants were explicitly informed that supplemental hormones were associated with increased cardiovascular risks. That information was also given extensive publicity. CONCLUSIONS: Detection bias could not be ruled out in either WHI study, and there may have been systematic overestimation of the risks of cardiovascular outcomes associated with the use of combined hormone therapy. To a limited extent, an analysis of the clinical trial data according to blinding status might be informative in determining whether detection bias could have given rise to overestimation of the overall and duration-specific risks in both WHI studies. If numbers permit, comparisons within strata of severity might also be informative. If the risks were overestimated in the WHI studies, a duration-related protective effect of combined hormone therapy on the risk of coronary heart disease and stroke may have gone undetected.

Aged↗
PubMed2005

Repeated topical treatment, in contrast to single oral doses, with Vitamin A-containing preparations does not affect plasma concentrations of retinol, retinyl esters or retinoic acids in female subjects of child-bearing age.

BACKGROUND: Vitamin A is widely used in cosmetic preparations. Given that oral Vitamin A and its metabolites present a potential reproductive risk, the present study investigated the effect of topical Vitamin A on human endogenous plasma levels of Vitamin A and its metabolites. METHODS: Two groups of 14 female volunteers of child-bearing age were kept on a Vitamin A-poor diet and treated topically for 21 days with creams containing 0.30% retinol or 0.55% retinyl palmitate on approximately 3000 cm2 of their body surface area, amounting to a total of approximately 30,000 IU Vitamin A/subject/day. After a 12-day wash-out period, the study groups received single oral doses of 10,000 IU or 30,000 IU retinyl palmitate (RP), corresponding to the maximal EU allowance during pregnancy or three-times higher, respectively. Blood samples were collected over 24h on study days -3 (pre-study), 1, 21 (first and last days of topical treatment) and 34 (oral administration) at 0, 1, 2, 4, 6, 8, 12, 14-16 h and 24 h after treatment for determination of plasma concentrations of retinol (REL), retinyl palmitate (RP), oleate (RO) and stearate (RS), 9-cis-, 13-cis-, all-trans- (AT), 13-cis-4-oxo- or AT-4-oxo-retinoic acids (RAs). RESULTS: With the exception of transient mild (RP-group) to moderate (REL-group) local irritation on the treatment sites, no adverse local or systemic effects were noted. On days 1 or 21 of topical treatment, no changes were measured in individual or group mean plasma Cmax, AUC0-24 h or other pharmacokinetic parameters of REL, retinyl esters or RAs relative to pre-study data. In contrast, single oral doses of RP at 10,000 IU or 30,000 IU produced dose-related and sustained increases in Cmax and AUC0-24 h values of plasma RP, RO, RS, 13-cis- and 13-cis-4-oxo-RAs, as well as a transient increase in AT-RA. In conclusion, our results provide evidence that human topical exposure to retinol- or retinyl ester-containing cosmetic creams at 30,000 IU/day and maximal use concentrations do not affect plasma levels of retinol, retinyl esters or RAs, whereas single oral doses at 10,000 IU or 30,000 IU produce significant increases in plasma retinyl esters and RAs.

Administration, Oral↗
PubMed2005

Hormone replacement therapy: pathobiological aspects of hormone-sensitive cancers in women relevant to epidemiological studies on HRT: a mini-review.

Hormone replacement therapy (HRT) has gained widespread and in some areas indiscriminate use. In reference to recent epidemiological studies which showed unexpected and controversial associations of HRT use with malignant tumours, here we review the current understanding of the dynamics of tumour growth. The pathomorphological characteristics and sex hormone sensitivity of cancers of the breast, endometrium, ovary and colon are discussed. The development of cancer from the first malignant tumour cell to clinical diagnosis takes many years. Hormones can influence tumour growth, but it is questionable whether hormones induce malignant tumours de novo. It is much more likely that hormones 'merely' promote the growth of already existing tumour cells. The long developmental process of tumours is in apparent contradiction to results of some epidemiological studies that describe an increased cancer risk, implying primary initiation, in HRT users within observation periods of 1-6 years. The mechanisms of initiation versus promotion of hormone-sensitive cancers, particularly breast cancer, are only partly understood. The conventional methods of epidemiological studies cannot detect potential risk factors without bias if they do not include a pathomorphological component on growth characteristics. The results of previous studies should be interpreted with great caution with regard to tumour biology.

Estrogen Replacement Therapy↗
PubMed2005

Multicenter randomized clinical trial comparing surgery and collagen injections for treatment of female stress urinary incontinence.

OBJECTIVES: To compare, in a multicenter, randomized clinical trial, collagen injections versus surgery with regard to efficacy, quality of life, satisfaction, and complications. METHODS: Of 133 women with stress urinary incontinence, 66 were randomized to collagen injection and 67 to surgery (6 needle bladder neck suspensions, 19 Burch, and 29 slings). After randomization, 15 women refused their allocated treatment. "Intent-to-treat" and "per protocol" analyses were applied. Women assigned to collagen injection could receive up to three injections before it was considered a failure. A "top-up" injection was allowed within 3 months after cure. Success as the primary outcome at 12 months was defined as a dry 24-hour pad test (2.5 g or less of urine) after having received only the allocated intervention. RESULTS: The per protocol analysis showed that the success rate 12 months after collagen injections (53.1%) was much lower than that after surgery (72.2%). The difference was 19.1% (95% confidence interval -36.2% to -2%). The general and disease-specific quality-of-life scores measured by the Rand Medical Outcomes Study 36-item Health Survey and Incontinence Impact Questionnaire were similar in the two groups (P = 0.306). Women treated by surgery were, on average, more satisfied (79.6%) than those treated by collagen injection (67.2%), but the difference was not significant (P = 0.228). Finally, complications were less frequent and severe with collagen injection: 36 events in 23 subjects for collagen injection versus 84 events in 34 subjects for surgery (P = 0.03). CONCLUSIONS: One year after intervention, the success rate of collagen injection as a treatment for stress urinary incontinence was about 19% lower than that after surgery. This has to be tempered by the similar changes in quality of life and satisfaction in both groups and that the number and severity of complications were much greater after surgery than after collagen injection. The results of this study indicate that collagen injections might be a worthwhile alternative to surgery for the treatment of stress urinary incontinence.

Collagen↗
PubMed2005

The 6-min walk test (6MW) as an efficacy endpoint in pulmonary arterial hypertension clinical trials: demonstration of a ceiling effect.

BACKGROUND: PAH trials traditionally use 6MW as the primary endpoint. Concerns regarding a "ceiling effect" masking efficacy have led to exclusion of patients with milder disease from most trials (BL 6MW>450 m). STRIDE I evaluated the selective endothelin A receptor antagonist, sitaxsentan (SITAX), in a 12-week randomized, double-blind, trial (178 patients) employing placebo (PBO), 100 mg or 300 mg SITAX orally once daily in PAH and included patients with NYHA class II, congenital heart disease and a BL 6MW>450 m, groups often excluded from previous trials. METHODS: We analyzed 6MW effects For All Pts (intention-to treat) and those meeting Traditional enrollment criteria, defined as patients with NYHA class III or IV and 6MW< or =450 m at BL with idiopathic PAH or PAH related to connective tissue disease. The 100 mg and 300 mg SITAX arms are pooled based on similar treatment effects on 6MW. CONCLUSION: Existence of a "ceiling effect" is supported by these data. The magnitude of the treatment effect and statistical power when using 6MW as the endpoint. Comparisons between PAH trials that do not adjust for the effects of differing enrollment criteria require caution.

Double-Blind Method↗
PubMed2005

A 10-year median follow-up study after allogeneic stem cell transplantation for chronic myeloid leukemia in chronic phase from HLA-identical sibling donors.

We report long-term outcome in 102 patients with cCML transplanted from an HLA-identical sibling donor from 1982 to 1998. The conditioning regimen was based on cyclophosphamide associated with either total body irradiation (TBI) (37 patients) or with busulfan (63 patients). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporin and methotrexate in the majority of the patients. Fifteen year overall survival was estimated at 53% (95% confidence interval (CI), 44-65) with a plateau after 2.5 years. Long-term survival was adversely affected by: longer time from chronic myeloid leukemia (CML) diagnosis to transplantation, older age at time of transplantation and GvHD (acute grade III-IV or chronic extensive). The main cause of death was infection, related to GvHD in 69% of patients. Splenectomy also significantly increased the risk of bacterial infection. 15-year relapse was estimated at 8% (95% CI, 0.1-14). Late malignancies occurred in seven patients, four of whom had an invasive cancer. Other frequent late complications included cataracts, psychological depression, osteonecrosis and hypothyroidism. These complications were more frequent following splenectomy, TBI and in patients with chronic extensive GvHD. We conclude that allogeneic transplantation with a related donor can cure more than half of CML patients in chronic phase, although physicians should be alert to long-term complications.

Follow-Up Studies↗
PubMed2004

[Effects of HRT on the risks of breast cancer and cardiovascular disease: the validity of the epidemiological evidence].

Publication of the findings of the Women's Health Initiative, in July 2002, the second link of the triptych made up of the Collaborative Reanalysis, in 1997, and the Women Million Study, in 2003, shortly after the WHI, seems to have tolled the knell of HRT, by claiming that women using HRT and combined therapy, have an increased risk of breast cancer and cardiovascular disease. As a result, the risk-benefit ratio would be reversed to the detriment of HRT. Over and above the legitimate questioning on the validity of these studies, such as calling into question their indisputable biases, especially the detection bias and hereby analysed in its spoiling the three randomised essays-there is the crucial question: can epidemiology make any headway in elucidating the hormonal aetiology of breast cancer? Indeed, given the low relative risks that have been observed, on the one hand, coupled with a whole set of methodological limitations, it is impossible to distinguish between bias and causation as alternative explanations for the observed associations. Above all, what emerges from this investigation is that, as far as HRT effects especially on breast cancer are concerned, epidemiological evidence only is inadequate, and collaborative research between histopathology and epidemiology is necessary.

Bias↗
PubMed2004

Does previous infection protect against atopic eczema and recurrent wheeze in infancy?

BACKGROUND: Frequent infection in infancy and early childhood has been hypothesized to explain the low prevalence of asthma and other atopic disease among children in developing countries (the so-called 'hygiene hypothesis'), but the low prevalence in Eastern Europe remains unexplained. OBJECTIVE: To test the hygiene hypothesis in the Republic of Belarus by examining the relationship between gastrointestinal (GI) and respiratory infection and two potentially atopic outcomes in the first 12 months of life: atopic eczema and recurrent wheeze. METHODS; We carried out two case-control studies nested within a large (n=17 046) randomized trial in Belarus, with cases defined as (1) first occurrence of atopic eczema (n=819) and (2) second episode of wheezing (n=112). Incidence density sampling was used to select four matched controls born within 1 month at the same hospital as the case. Exposure was defined as one or more episodes of GI or respiratory infection (examined separately) with onset >7 days before onset of the case's atopic outcome. Analyses controlled for family atopic history, duration of exclusive breastfeeding, sex, birth weight, maternal education, and (for recurrent wheeze) maternal smoking. RESULTS: For atopic eczema, prior GI infection occurred in 7.4% of cases vs. 6.0% of controls [adjusted OR=1.27 (0.94-1.72)] and prior respiratory infection in 35.2% vs. 32.6% [adjusted OR=1.14 (95% CI=0.94-1.37)]. For recurrent wheeze, prior GI infection occurred in 9.8% of cases vs. 7.4% of controls [adjusted OR=1.30 (0.60-2.82)]. CONCLUSION: Our results do not support the hypothesis that infection protects against atopic eczema or recurrent wheezing in the first 12 months of life.

Adult↗
PubMed2004

Efficacy of BAL5788, a prodrug of cephalosporin BAL9141, in a mouse model of acute pneumococcal pneumonia.

BAL5788 is a water-soluble prodrug of BAL9141, a new broad-spectrum cephalosporin with high levels of in vitro activity against methicillin- and vancomycin-resistant staphylococci and penicillin-resistant streptococci. In plasma BAL5788 is rapidly converted to BAL9141. We studied the activity of BAL5788 in a mouse model of acute pneumococcal pneumonia. Leukopenic female Swiss albino mice were challenged intratracheally with 10(7) CFU of clinical Streptococcus pneumoniae strains P-52181 (Pen(s) Cro(s) Ctx(s)), P-15986 (Pen(r) Cro(s) Ctx(s)), P-40422 (Pen(r) Cro(r) Ctx(r)), and P-40984 (Pen(r) Cro(r) Ctx(r)). Infected mice received subcutaneous (s.c.) injections of BAL5788 or ceftriaxone starting 3 h after pneumococcal challenge. Uninfected nonleukopenic mice received single s.c. doses of BAL5788 to determine the BAL9141 concentration-time profiles in serum and lungs. Untreated control mice died within 5 days postinfection. Ten-day cumulative survival rates for infected mice receiving BAL5788 (total daily doses of BAL9141 equivalents, 2.1 to 75 mg/kg of body weight) ranged from 57 to 100%, whereas with ceftriaxone (total daily doses, 10 to 400 mg/kg), the survival rates varied between 13 and 100%. In mice infected with P-15986, the survival rates achieved with BAL5788 (BAL9141 equivalent, 8.4 mg/kg) and those achieved with ceftriaxone (50 mg/kg) were significantly different (93 versus 13%; P < 0.0001) in favor of BAL5788; the outcomes of the trials with all other strains were not significantly different between the two antibiotics, but markedly lower doses of BAL5788 than ceftriaxone were required to obtain similar survival rates. Pharmacokinetic data showed that BAL9141 was effective against the four pneumococcal strains tested at very low values of the time above the MIC (T > MIC), which ranged from 9 to 18% of the dosing interval, whereas the values of T > MICs for ceftriaxone ranged from 30 to 50% of the dosing interval.

Animals↗
PubMed2003

Limited Pap screening associated with reduced risk of cervical cancer in South Africa.

BACKGROUND: We investigated the effect of Pap smear screening on the incidence of invasive cancer of the cervix in the Western Cape, South Africa where screening is limited. METHODS: Data were derived from a case-control study of the association of hormonal contraceptives and invasive cervical cancer. Incident cases (n = 524) of invasive cervical cancer who presented at two tertiary hospitals and controls (n = 1540) series matched for age, race, and place of residence were interviewed. Information on a wide range of variables was collected including whether the women had previously had a Pap smear taken and the number and timing of smears. Odds ratios (OR) and 95% CI were calculated using multiple logistic regression. RESULTS: The OR of cervical cancer was reduced among women who had ever had a smear (OR = 0.3, 95% CI: 0.3-0.4). The OR declined with increasing number of smears to 0.2 for >/=>3 smears (trend P = 0.0003). Among women who had a smear <5 years previously the OR was 0.3, but even if the smear was taken >/=15 years previously the women remained at reduced risk (OR = 0.5). CONCLUSION: The data suggest that even limited Pap smear screening reduces the risk of cervical cancer. Should a screening programme be successfully implemented, the incidence of cervical cancer might be reduced by as much as 70%.

Adult↗
PubMed2003

Risks of estrogen plus progestin therapy: a sensitivity analysis of findings in the Women's Health Initiative randomized controlled trial.

CONTEXT: The Women's Health Initiative (WHI) randomized controlled trial that compared estrogen plus progestin versus placebo was stopped because of a significantly increased risk of breast cancer in the active treatment group (reason 1), and because a global index supported a finding of overall harm (reason 2). The possibility that the findings could have been accounted for by bias was not considered. OBJECTIVE: The present analysis was undertaken to determine whether detection bias is a plausible alternative to causality as an explanation for those findings that contributed to the reasons for discontinuing the study. DESIGN: setting and participants: This work took the form of a sensitivity analysis of the published WHI data to determine the magnitude of the detection bias required to account for those findings that contributed to the two reasons for stopping the study. MAIN OUTCOME MEASURES: These were differences in incidence rates of breast cancer (reason 1), and breast cancer, coronary heart disease, stroke and pulmonary embolism (reason 2), among estrogen plus progestin and placebo recipients. RESULTS: In the WHI study, 44.4% of the women on active treatment, as against 6.8% of the placebo recipients, had their treatments unblinded (mainly because of vaginal bleeding). Among them, detection bias could not be excluded. For the three cardiovascular outcomes, bias became a strong likelihood after the women were twice cautioned about possible increased risks observed in the interim data among estrogen plus progestin recipients. On the null hypothesis, bias could have accounted for the observed associations if, on average, it augmented the detection of disease that would otherwise have gone undiagnosed by 0.7-0.8/1000 per year. CONCLUSIONS: For differences in incidence of the order of 0.7-0.8/1000 per year, it is not possible to discriminate between causation and detection bias as alternative explanations for the findings.

Bias↗
PubMed2002

A MAS-NMR study of the location of (+)-totarol, a diterpenoid bioactive molecule, in phospholipid model membranes.

(+)-Totarol, a diterpenoid isolated from Podocarpus spp., is a potent antioxidant and antibacterial agent. Although the mechanism of action of this hydrophobic molecule is poorly understood, recent work from our laboratories suggests that it could be due to membranotropic interactions. The location of (+)-totarol in membranes and its interaction with membrane components is therefore of considerable interest. High resolution magic angle spinning (MAS) natural abundance 13C nuclear magnetic resonance studies were undertaken to assess the location of (+)-totarol in model membranes composed of egg yolk phosphatidylcholine (EYL). 13C spin-lattice relaxation times (T(1)) of both the phospholipid and (+)-totarol molecules in the presence of Gd(3+) were measured to obtain information on molecular distances. Our results indicate that (+)-totarol is situated in the upper region of the membrane, with its hydroxyl group located in the vicinity of the C-3/4 carbon atoms of the phospholipid acyl chain, and nearly perpendicular with respect to the phospholipid acyl chain axis. Such a location of (+)-totarol in the membrane would be expected to compromise the functional integrity of the membrane and account, at least in part, for its antibacterial effects.

Abietanes↗
PubMed2001

Clinical outcomes resulting from telemedicine interventions: a systematic review.

BACKGROUND: The use of telemedicine is growing, but its efficacy for achieving comparable or improved clinical outcomes has not been established in many medical specialties. The objective of this systematic review was to evaluate the efficacy of telemedicine interventions for health outcomes in two classes of application: home-based and office/hospital-based. METHODS: Data sources for the study included deports of studies from the MEDLINE, EMBASE, CINAHL, and HealthSTAR databases; searching of bibliographies of review and other articles; and consultation of printed resources as well as investigators in the field. We included studies that were relevant to at least one of the two classes of telemedicine and addressed the assessment of efficacy for clinical outcomes with data of reported results. We excluded studies where the service did not historically require face-to-face encounters (e.g., radiology or pathology diagnosis). All included articles were abstracted and graded for quality and direction of the evidence. RESULTS: A total of 25 articles met inclusion criteria and were assessed. The strongest evidence for the efficacy of telemedicine in clinical outcomes comes from home-based telemedicine in the areas of chronic disease management, hypertension, and AIDS. The value of home glucose monitoring in diabetes mellitus is conflicting. There is also reasonable evidence that telemedicine is comparable to face-to-face care in emergency medicine and is beneficial in surgical and neonatal intensive care units as well as patient transfer in neurosurgery. CONCLUSIONS: Despite the widespread use of telemedicine in virtually all major areas of health care, evidence concerning the benefits of its use exists in only a small number of them. Further randomized controlled trials must be done to determine where its use is most effective.

Humans↗
PubMed2001

SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo.

We describe here the identification and properties of SCH-C (SCH 351125), a small molecule inhibitor of HIV-1 entry via the CCR5 coreceptor. SCH-C, an oxime-piperidine compound, is a specific CCR5 antagonist as determined in multiple receptor binding and signal transduction assays. This compound specifically inhibits HIV-1 infection mediated by CCR5 in U-87 astroglioma cells but has no effect on infection of CXCR4-expressing cells. SCH-C has broad and potent antiviral activity in vitro against primary HIV-1 isolates that use CCR5 as their entry coreceptor, with mean 50% inhibitory concentrations ranging between 0.4 and 9 nM. Moreover, SCH-C strongly inhibits the replication of an R5-using HIV-1 isolate in SCID-hu Thy/Liv mice. SCH-C has a favorable pharmacokinetic profile in rodents and primates with an oral bioavailability of 50-60% and a serum half-life of 5-6 h. On the basis of its novel mechanism of action, potent antiviral activity, and in vivo pharmacokinetic profile, SCH-C is a promising new candidate for therapeutic intervention of HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed2001

Discovery of 4-[(Z)-(4-bromophenyl)- (ethoxyimino)methyl]-1'-[(2,4-dimethyl-3- pyridinyl)carbonyl]-4'-methyl-1,4'- bipiperidine N-oxide (SCH 351125): an orally bioavailable human CCR5 antagonist for the treatment of HIV infection.

Structure-activity studies on piperidino-piperidine 3 led to the discovery of SCH 351125 (1), a selective CCR5 antagonist with potent activity against RANTES binding (K(i) = 2 nM), which possesses subnanomolar activity in blocking viral entry and has excellent antiviral potency versus a panel of primary HIV-1 viral isolates. Compound 1, which has good oral bioavailability in rats, dogs, and monkeys, is proposed as a potential therapeutic agent for the treatment of HIV-1 and has entered human clinical trials.

Administration, Oral↗
PubMed2001

Membranotropic effects of the antibacterial agent Triclosan.

Triclosan is a broad-spectrum hydrophobic antibacterial agent used in dermatological preparations and oral hygiene products. To gain further insight into the mode of action of Triclosan we examined its effects on membranes by performing leakage titrations of different oral bacteria and studying its interaction with model membranes through the use of different biophysical techniques. There was negligible efflux of intracellular material from Streptococcus sobrinus at the minimal inhibitory concentration of Triclosan; whatever leakage did occur commenced only at much higher concentrations. In contrast, no leakage was observed at even the minimal bactericidal concentration for Porphyromonas gingivalis. Triclosan decreased the onset temperature of the gel to liquid-crystalline phase transition of 1,2-dimyristoyl-sn-glycero-3-phosphocholine and 1,2-dimyristoyl-sn-3-[phospho-rac-glycerol] membranes and was immiscible with these lipids in the fluid phase at concentrations greater than 5 mol%. Steady-state fluorescence anisotropy measurements of different phospholipid/Triclosan samples using 3-(p-6-phenyl-1,3,5-hexatrienyl)-phenylpropionic acid were consistent with the calorimetric data. Incorporation of increasing amounts of Triclosan into 1,2-dielaidoyl-sn-glycero-3-phosphoethanolamine (DEPE) vesicles induced the nonlamellar H(II) hexagonal phase at low temperatures and new immiscible phases at temperatures below the main transition of DEPE. Taking these results together suggests that the antibacterial effects of Triclosan are mediated at least in part through its membranotropic effects, resulting in destabilized structures which compromise the functional integrity of cell membranes without inducing cell lysis.

Anti-Infective Agents, Local↗