How safe is off-label use of imiquimod in oral lesions?

DATA SOURCES: A comprehensive search was conducted on PubMed and Embase, adhering to the principles outlined in the PRISMA Extension for Scoping Reviews (PRISMA-ScR). The search strategy was subsequently registered on PROSPERO. STUDY SELECTION: Articles were chosen based on an analysis of titles and abstracts, with no restrictions on publication date, language, or participant age. In vitro studies, animal studies, and literature reviews were excluded from consideration. DATA EXTRACTION AND SYNTHESIS: Clinical trials in humans, case reports, or case series that reported the use of imiquimod for treating conditions in the oral or labial mucosa were included in this study. Results from duplicate articles were excluded from the analysis. RESULTS: Out of a total of 601 references initially identified, only 28 studies were included in the review. These studies were classified based on the use of imiquimod into three groups: potentially malignant disorders and oral cancer, lesions related to HPV, and autoimmune conditions. In all cases presented in the article, there is an occurrence of both local and systemic side effects. CONCLUSIONS: The study elucidated the off-label use of imiquimod in oral pathologies, whether potentially malignant, cancerous, autoimmune, or associated with HPV infection. However, it was observed that further research is warranted for the development of a specific formulation for the oral mucosa, ensuring the drug's sustained presence at its active site of action without interference from saliva and minimizing potential side effects.

Is there evidence that e-cigarettes promote an increased risk of dental caries?

DATA SOURCES: This study was conducted on a sample of patients who attended the dental clinic at Tufts University School of Dental Medicine, between January 1, 2019 and January 1, 2022. Ethical approval was obtained before commencing the research. STUDY SELECTION: This cross-sectional study was carried out through an electronic search of electronic records. It includes patients aged over 16 years, both electronic cigarette (e-cigarettes) users and non-users, with recorded caries risk assessments. Patients with a history of recreational drug use or lacking a caries diagnosis were excluded. The Caries Management by Risk Assessment (CAMBRA) was utilized to indicate and classify caries risk. DATA EXTRACTION AND SYNTHESIS: Descriptive statistics, multivariate and bivariate analyzes were used to assess the relationship between use of e-cigarettes and caries risk level. SPSS software, Version 26 (IBM) was used in the analysis with significance level set at α = 0.05. RESULTS: Out of a total of 13,216 patients included in the research, 13,080 (99.3%) self-declared as non-users of e-cigarettes, and 136 (0.69%) were e-cigarette users. There was a statistically significant difference (P < 0.001) in caries risk levels between e-cigarette users (6.6% low, 14.3% moderate, and 79.1% high caries risk level) and control group (14.5% low, 25.9% moderate, and 59.6% high caries risk level). CONCLUSIONS: The study provides evidence supporting the notion that e-cigarette users exhibit a high level of caries risk.

Impacts of smoking on oral health-what is the role of the dental team in smoking cessation?

DATA SOURCES: Electronic searches were conducted on databases (PubMed, EMBASE, and Google Scholar). In addition, websites of national organisations (US Food and Drug Administration, National Cancer Institute, Centres for Disease Control and Prevention, American Dental Association, Office of Disease Prevention and Health Promotion, National Institute on Drug Abuse, Agency for Healthcare Research and Quality) were also searched. STUDY SELECTION: To achieve the objectives of the study, systematic reviews, controlled clinical trials, and observational studies published between October 2021 and February 2022 were considered. DATA EXTRACTION AND SYNTHESIS: This narrative review included articles which investigated the role of Dentistry professionals and their impact on smoking cessation and the effects resulting from tobacco use on oral health. RESULTS: The review revealed that smokers have a significantly higher likelihood of developing oral cancer (95% CI: 3.19-6.77) compared to non-smokers. Passive smokers also have an increased risk (1.51 times) of developing oral cancer (95% CI: 1.20-1.91). Additionally, smokers have an 80% increased risk of periodontitis (RR = 1.82; 95% CI: 1.43-2.31), an 85% worsened periodontal condition (RR = 1.85; 95% CI: 1.5-2.2), and a 36.6% increase in caries prevalence (OR = 1.84; 95% CI: 1.64-2.07). Smoking is also associated with a higher potential for dental implant failure in a dose-dependent manner. Brief educational interventions by the dental team resulted in a smoking cessation rate of 74/1000 individuals versus 27/1000 individuals in the control group. When combined with pharmacological therapy, these interventions may lead to an additional 50 to 70% increase in long-term smoking abstinence. CONCLUSIONS: Smoking is strongly linked to an increased risk of oral cancer, dental caries, implant failure, and periodontal disease. Dental teams play a vital role in identifying and addressing oral pathologies related to smoking and providing necessary care for smoking cessation. Brief educational interventions, either alone or in combination with pharmacotherapy, offer valuable approaches for the dental team to support smoking cessation. However, establishing a comprehensive training and continuing education program is crucial to integrate dental professionals into a multidisciplinary smoking cessation program.

Electronic nicotine delivery systems (ENDS): a strategy for smoking cessation or a new risk factor for oral health?

DATA SOURCES: A search was conducted in PubMed and Cochrane Library databases for articles published in English between January 2012 and October 2022. STUDY SELECTION: Articles were selected using both the term "electronic nicotine delivery system" (ENDS), as per the Medical Subject Heading (MeSH), in conjunction with specific oral domains. In vitro studies, animal models, unregistered clinical trials, and articles with conflicts of interest were excluded. DATA EXTRACTION AND SYNTHESIS: Clinical and public health studies comparing ENDS users, smokers, and non-smokers in the context of oral-related diseases were included. Results from duplicate articles were not considered. RESULTS: The study indicates a potential carcinogenic effect due to cytogenotoxicity from intrinsic components of ENDS. However, this does not establish ENDS as an independent risk factor for oral cancer. ENDS use may alter the oral microbiome, leading to increased biofilm adhesion and potential associations with caries, periodontal disease, and peri-implantitis. The wide variety of flavors available in the ENDS market is a significant factor influencing initiation and long-term use by young people. CONCLUSIONS: ENDS users are susceptible to periodontal disease, caries, soft tissue injuries, and changes in tooth and prosthesis coloration. The chemical components in ENDS can induce cellular changes associated with a potential risk of oral cancer. However, more long-term studies are required to fully understand the impact of ENDS use on oral health.

Exposure to low-dose bisphenol A induces spleen damage in a murine model: Potentially through oxidative stress?

Background: During early life, exposure to environmental toxicants, including endocrine disruptor bisphenol A (BPA), can be detrimental to the immune system. To our knowledge, a few researches have looked at the effects of developing BPA exposures on the spleen. Aim: The murine model was developed to investigate the underlying molecular mechanisms and mode of BPA actions on the spleen subsequent to prolonged early-life exposure to BPA. Methods: Immature (3-week-old) male and female Swiss Albino mice were intraperitoneally injected with 50 µg/kg BPA in corn oil or corn oil alone for 6 weeks. Mouse spleens were harvested and examined histologically at 10 weeks old (adulthood). Results: We observed neurobehavioral impairments and a significant increase in peripheral monocyte and lymphocyte counts in mice (males and females). Moreover, several spleen abnormalities in both male and female mice were observed in adulthood. BPA-treated mice's histopathological results revealed toxicity in the form of significantly active germinal centers of the white pulp and a few apoptotic cells. There was also a notable invasion of the red pulp by eosinophils and lymphocytes that were significantly higher than normal. Agarose gel electrophoresis provided further evidence of internucleosomal DNA fragmentation and apoptosis in the splenic tissues of BPA-treated mice compared to controls. In addition, there were increased levels of the lipid peroxidation malondialdehyde end-product, a marker of oxidative lipid damage, in the spleens of BPA-treated mice compared to controls. Conclusion: Our study provides evidence that oxidative stress injury induced by early-life exposures to BPA could contribute to a range of splenic tissue damages during adulthood.

COVID-19 pandemic: multilevel dental technical guidelines based on new scientific evidence.

The COVID-19 pandemic imposed restrictive measures on dentistry in different regions of the world, ranging from stoppage of care to only permission for urgent and emergency dental services. Thus, new biosafety guidelines for resuming activities, whether in single dental offices, large clinics or dental education activities, are urgently required. In this sense, herein, guidelines that incorporate common points of the main protocols found in the literature for the resumption of dental activities at their different levels, whether in the scope of care or education, are presented. Furthermore, we present the incorporation of measures that allow an increase in the level of biosafety, such as the control of the dental team, the inclusion in the history of conjunctivitis as a possible alert for COVID-19, and the use of the pulse oximeter to assess the risk of silent hypoxemia, which may indicate a complication of COVID-19. In addition, new perspectives for directing research and innovation for biosafety in dentistry are discussed.

Real world use of oral treatments in interstitial cystitis/bladder pain syndrome in the UK: Outcome of a cross sectional study.

BACKGROUND: To describe the oral treatments people living with interstitial cystitis/bladder pain syndrome (IC/BPS) are using to treat their urologic condition in the UK. METHOD: A questionnaire hyperlink encompassing current and previous medications taken for IC/BPS with other sociodemographic and diagnostic indices was available to the Bladder Health UK website. Interested and fully consented individuals accessed and completed the survey. RESULTS: A total of 601 accessed the questionnaire of whom 173 participants responded (response rate: 28.7%) with a mean ± SD O'Leary/Sant scores of 20.12 ± 9.38. A sample size of 171 was estimated to be used in the survey. A fifth of the participants were not on any treatment at all. Amitriptyline was the most prevalent medication in use both alone and in combination. A shift in the use of unapproved (for IC/BPS) antidepressant, smooth muscle relaxant, opioids, gabapentenoids, and antibiotics was observed in the sample. There were no significant differences between the mean (SD) O'Leary/Sant scores of cohorts currently taking oral medications and those not taking it. More than two-thirds of the participants had been diagnosed with the disease more than 5 years. Just under a half (47.4%) of participants reported a history of allergy. CONCLUSION: Our study provides contemporary evidence that the treatments used for managing IC/BPS encompass a broad range of medications both recommended and not recommended by current guidelines. The latter suggests patients are willing to try novel treatments when more conventional ones are ineffective.

COVID-19 pandemic: multilevel dental technical guidelines based on new scientific evidence

ABSTRACT The COVID-19 pandemic imposed restrictive measures on dentistry in different regions of the world, ranging from stoppage of care to only permission for urgent and emergency dental services. Thus, new biosafety guidelines for resuming activities, whether in single dental offices, large clinics or dental education activities, are urgently required. In this sense, herein, guidelines that incorporate common points of the main protocols found in the literature for the resumption of dental activities at their different levels, whether in the scope of care or education, are presented. Furthermore, we present the incorporation of measures that allow an increase in the level of biosafety, such as the control of the dental team, the inclusion in the history of conjunctivitis as a possible alert for COVID-19, and the use of the pulse oximeter to assess the risk of silent hypoxemia, which may indicate a complication of COVID-19. In addition, new perspectives for directing research and innovation for biosafety in dentistry are discussed.

COVID-19 Vaccines: Bioethical Consideration / Vacunas contra la covid-19: consideración bioética / Vacinas contra a covid-19: consideração bioética

Abstract The COVID-19 pandemic produced immeasurable impacts on the economy, education, and socialization, besides the loss of mi llions of lives. Thus, there has been an accelerated development of an unprecedented number of COVID-19 vaccine candidates to control the pandemic. The World Health Organization's emergency use authorization of COVID-19 vaccines still in clinical trial allowed immunizing the population. This paper presents a perspective of the bioethical precepts of autonomy, non-maleficence, beneficence, and justice in the emergency use of COVID-19 vaccines. Furthermore, it emphasizes the importance of surveillance at all stages of vaccine development to detect adverse effects and ensure compliance with bioethical precepts.

Resumen La pandemia de la covid-19 ha tenido impactos inconmensurables en la economía, la educación y la socialización, además de la pérdida de millones de vidas. Por lo tanto, se ha acelerado el desarrollo de un número sin precedentes de candidatos a vacunas contra la covid-19 para controlar la pandemia. A su vez, la autorización para su uso de emergencia por parte de la Organización Mundial de la Salud permitió el inicio de la inmunización de la población a través de vacunas que aún se encuentran en ensayos clínicos. Aquí presentamos una perspectiva de los preceptos bioéticos de autonomía, no maleficencia, beneficencia y justicia en el contexto del uso de emergencia de vacunas contra la covid-19. Además, se enfatiza la importancia de la vigilancia en todas las etapas del desarrollo de la vacuna con el fin de detectar efectos adversos y asegurar el cumplimiento de los preceptos bioéticos.

Resumo A pandemia ocasionada pela covid-19, além da perda de milhões de vidas, vem trazendo consequências incomensuráveis para a economia, a educação e a socialização. Portanto, vem sendo acelerado o desenvolvimento de um número sem precedentes de candidatos a vacinas contra a covid-19 para controlar a pandemia. Por sua vez, a autorização para seu uso emergencial por parte da Organização Mundial da Saúde permitiu o início da imunização da população por meio de vacinas que ainda se encontram em ensaios clínicos. Aqui, apresentamos uma perspectiva dos princípios bioéticos de autonomia, não maleficencia, beneficência e justiça no contexto do uso emergencial de vacinas contra covid-19. Além disso, é enfatizada a importância da vigilância em todas as etapas do desenvolvimento da vacinação a fim de detectar efeitos adversos e assegurar o cumprimento dos princípios bioéticos.

The relationship between illness perception and worsening of interstitial cystitis/painful bladder syndrome symptoms: A cross-sectional study.

OBJECTIVE: To evaluate disease perception in a cohort of patients with interstitial cystitis/painful bladder syndrome (IC/PBS) using the Brief Illness Perception-Questionnaire (BIP-Q) and to evaluate how this might relate to disease severity. MATERIALS AND METHODS: The study is a cross-sectional survey amongst members of Bladder Health UK who had previously received a clinical diagnosis of IC/PBS. A hyperlink containing the questionnaire was sent to the patient group's website and interested members accessed and completed the survey. Participants' inclusion was based on a prior clinical diagnosis of IC/PBS, current O'Leary Sant scores supportive of the diagnosis, and age between 18 and 80. A sample size of 171 was used in the study. The Brief Illness Perception Questionnaire (BIP-Q) and the O'Leary/Sant symptoms and problem indices questionnaire were used to collect data. A multivariable logistic regression analysis was used to test the relationship between items of BIP-Q and severity of IC/PBS. Content analysis was used for the causal domain and subsequently analysed as percentages. RESULTS: Six hundred and one members accessed the questionnaire of whom 159 returned completed questionnaires. One hundred and twenty-two of 159 (≥75%) respondents believe that their illness will continue indefinitely. The majority of the respondents indicated that IC/PBS had a negative impact on their daily lives, caused them worry and made them emotionally unstable. Of the 8 BIP-Q items, those most predictive of disease severity were (adjusted odd ratio and confidence intervals): consequence 0.094 (0.023-0.386); treatment control 2.702 (1.256-5.812); identity 0.141 (0.033-0.600); concern 9.363 (1.521-57.632). CONCLUSIONS: Our findings show that IC/PBS negatively impacts participant's quality of life and emotional wellbeing. Higher expectation for treatment benefit and increasing levels of patient concern are predictive for severity of IC/PBS.

Adipocyte-Specific Fatty Acid-Binding Protein (AFABP) and Chemerin in Association with Gestational Diabetes: A Case-Control Study.

BACKGROUND: Adipocytokines participate in regulating the inflammatory response in glucose homeostasis and type 2 diabetes. However, among these peptides, the role of adipocyte-specific fatty-acid-binding protein (AFABP), chemerin, and secreted protein acidic and rich in cysteine (SPARC) in gestational diabetes (GDM) has not been fully investigated. METHOD: The maternal fasting level of adipocytokines of 53 subjects with GDM and 43 normal pregnant (NGDM) was measured using multiplex immunoassay at 24-28 weeks, before delivery, immediate postpartum, and 2-6 months postpuerperium. RESULTS: Higher levels of AFABP were associated with a 3.7-fold higher risk of GDM. Low chemerin levels were associated with a 3.6-fold higher risk of GDM. Interleukin-10 (IL-10) was inversely associated with the risk of GDM. SPARC had no association with GDM. AFABP was directly correlated to interleukin-6 (r = 0.50), insulin resistance index (r = 0.26), and body mass index (r = 0.28) and inversely correlated to C-reactive protein (r = -0.27). Chemerin levels were directly and strongly correlated with IL-10 (r = 0.41) and interleukin-4 (r = 0.50) and inversely correlated to insulin resistance index (r = -0.23) in GDM but not NGDM. In the longitudinal assessment, there were no significant differences in AFABP and chemerin concentrations of both studied groups. CONCLUSION: AFABP and chemerin were associated with a higher risk of GDM. These adipocytokines were related to insulin resistance, body mass index, and inflammation in pregnant women diagnosed with GDM.

Paternal bisphenol A exposure induces testis and sperm pathologies in mice offspring: Possibly due to oxidative stress?

Bisphenol A (BPA), an endocrine and metabolic disruptor, is widely used to manufacture polycarbonate plastics and epoxy resins. Accumulating evidence suggests that paternal BPA exposure adversely affects male germlines and results in atypical reproductive phenotypes that might persist for generations to come. Our study investigated this exposure on testicular architecture and sperm quality in mouse offspring, and characterised underlying molecular mechanism(s). A total of 18 immature male Swiss albino mice (3.5 weeks old) were randomly divided into three groups and treated as follows: Group I, no treatment (sham control); Group II, sterile corn oil only (vehicle control); Group III, BPA (400 µg/kg) in sterile corn oil. At 9.5 weeks old, F0 males were mated with unexposed females. F0 offspring (F1 generation) were monitored for postnatal development for 10 weeks. At 11.5 weeks old, the animals were sacrificed to examine testicular architecture, sperm parameters, including DNA integrity, and oxidative stress biomarkers. Results showed that BPA significantly induced changes in the body and testis weights of the F0 and F1 generation BPA lineages compared to F0 and F1 generation control lineages. A decrease in sperm count and motility with further, increased sperm abnormalities, no or few sperm DNA alterations and elevated levels of MDA, PC and NO were recorded. Similar effects were found in BPA exposed F0 males, but were more pronounced in the F0 offspring. In addition, BPA caused alterations in the testicular architecture. These pathological changes extended transgenerationally to F1 generation males' mice, but the pathological changes were more pronounced in the F1 generation. Our findings demonstrate that the biological and health BPA impacts do not end in paternal adults, but are passed on to offspring generations. Hence, linking observed testis and sperm abnormalities in the F1 generation to BPA exposure of their parental line was evident in this work. The findings also illustrate that oxidative stress appears to be a molecular component of the testis and sperm pathologies.

Increased plasma CD14 levels 1 year postpartum in women with pre-eclampsia during pregnancy: a case-control plasma proteomics study.

Epidemiological data suggest that pre-eclampsia (PE) is associated with an increased risk of post-delivery metabolic dysregulation. The aim of the present case-control observational study was to examine the global plasma proteomic profile 1 year postpartum in women who developed PE during pregnancy (n = 5) compared to controls (n = 5), in order to identify a novel predictive marker linking PE with long-term metabolic imbalance. Key findings were verified with enzyme-linked immunosorbent assay (ELISA) in a separate cohort (n = 17 women with PE and n = 43 controls). One hundred and seventy-two proteins were differentially expressed in the PE vs. control groups. Gene ontology analysis showed that Inflammatory|Immune responses, Blood coagulation and Metabolism were significantly enriched terms. CD14, mapping to the inflammatory response protein network, was selected for verification based on bibliographic evidence. ELISA measurements showed CD14 to be significantly increased 1 year postpartum in women with PE during pregnancy compared to controls [PE group (median ± SD): 296.5 ± 113.6; control group (median ± SD): 128.9 ± 98.5; Mann-Whitney U test p = 0.0078]. Overall, the identified proteins could provide insight into the long-term disease risk among women with PE during pregnancy and highlight the need for their postpartum monitoring. CD14 could be examined in larger cohorts as a predictive marker of insulin resistance and type II diabetes mellitus among women with PE.

Longitudinal assessment of D-dimer and plasminogen activator inhibitor type-1 plasma levels in pregnant women with risk factors for preeclampsia.

OBJECTIVE: Investigating D-Dimer/D-Di and plasminogen activator inhibitor type-1/PAI-1 levels throughout gestation in women with preeclampsia/PE risk factors. METHODS: D-Di and PAI-1 plasma levels were determined in 28 women at 12-19, 20-29, 30-34 and 35-40 weeks of gestation. RESULTS: D-Di was lower at 12-19 weeks and higher at 30-34 weeks in women who developed PE versus who did not develop it. D-Di increased throughout gestation in both groups, peaking earlier in pregnant women who developed PE versus who did not develop it. PA1-1 increased across gestation, but it didn't differ between groups. CONCLUSION: D-Di was able to discriminate these groups of women at 12-19 and 30-34 weeks of gestation.

Distribution of mast cell subtypes in interstitial cystitis: implications for novel diagnostic and therapeutic strategies?

AIMS: To identify the presence and geographical distribution of mast cell (MC) subtypes: MCT (tryptase positive-chymase negative) and MCTC (tryptase positive-chymase positive) in bladder tissue. METHODS: Bladder tissue was obtained from patients with painful bladder syndrome/interstitial cystitis (n=14) and normal histology from University Hospital Southampton tissue bank. Sequential tissue slices were immunohistochemically stained for MC subtypes using anti-MC tryptase (for MCT and MCTC) and anti-MC chymase (for MCTC). Stained sections were photographed, and positively stained MCs were quantified using ImageJ. Data were analysed using descriptive statistics and individual paired t-tests. RESULTS: There was a significant difference in the density of MCs between each layer of the disease bladder, with the greatest accumulation within the detrusor (p<0.001). There was a significant increase in MCTC subtype in the lamina (p=0.009) in painful bladder syndrome/interstitial cystitis. CONCLUSIONS: Our results suggest that mastocytosis is present within all layers of disease bladder, especially the muscle layer. The varying increase in MC subtypes in the lamina and mucosa may explain the variability in painful bladder syndrome/interstitial cystitis symptoms. A high influx of MCTC in the mucosa of individuals who also had ulceration noted within their diagnostic notes may be of the Hunner's ulcer subclassification. These findings suggest a relationship between the pathogenesis of MC subtypes and the clinical presentation of painful bladder syndrome/interstitial cystitis. A cohort study would further elucidate the diagnostic and/or therapeutic potential of MCs in patients with painful bladder syndrome/interstitial cystitis.

Systemic lupus erythematosus: disease activity may influence the release of endothelial microparticles?

: To evaluate blood-borne endothelial microparticles (EMPs) in women with SLE and correlated these to disease activity as defined by the SLEDAI-2K score. The study takes cross-sectional design. A total of 90 age-matched women were recruited including: G1 (healthy volunteers, n = 30), G2 (women with SLE and low disease activity (SLEDAI-2K score ≤4; n = 30) and G3 (women with SLE and moderate/high disease activity (SLEDAI-2K score >4; n = 30). Blood was collected in 3.2% sodium citrate. Subsequently, the microparticles were purified by ultracentrifugation and labeled with anti-CD51/61 and anti-Annexin-V antibodies. Quantification and phenotyping were performed using flow cytometry. The number of EMPs was significantly higher in SLE patients compared with controls (P = 0.0178). When SLE patients were stratified according to disease activity, the number of EMPs was significantly increased in women with moderate-to-high disease activity compared with controls (P = 0.0074). We observed a correlation between the number of EMPs and age (r = -0.34; P = 0.0123) and between the number of EMPs and SLEDAI-2K score (r = 0.30; P = 0.04). Our results suggest that the SLE causes increased EMPs release, especially in patients with SLEDAI-2K score greater than 4. Although measurement of the EMPs could be useful in distinguishing patients with SLE from health controls, they have limited value in differentiating between SLE subtypes.

FVIIa-antithrombin levels in early and late preeclampsia.

BACKGROUND: Preeclampsia (PE) is associated with a hypercoagulability state. According to the gestational age (GA) at the onset of the disease, PE has been classified as early (GA<34weeks) and late (GA≥34weeks). It has been admitted that early PE is associated with ischemic placental lesions, while in late PE an adequate or slightly impaired placentation occurs, which suggests that the two clinical forms have distinct etiology. Tissue factor (TF) binds and activates plasma factor VII triggering the coagulation. The inhibitor antithrombin (AT), along with tissue factor pathway inhibitor, acts as an inhibitor of the FVIIa-TF pathway. Once the TF-FVIIa complex is formed, the binding and transfer of FVIIa to AT is facilitated and FVIIa activity is inhibited. OBJECTIVE: We evaluated the FVIIa-AT complex levels in pregnant women with early and late severe PE (sPE), in order to verify if this biomarker can be useful for discriminating the two forms of the disease. METHODS: We evaluated 26 pregnant with severe early PE and 19 pregnant with severe late PE. FVIIa-AT levels were measured by STACLOT® (Diagnostica Stago). Statistical analysis was done by Mann-Whitney test. RESULTS: Increased FVIIa-AT levels were found in early sPE [148.4pM (137.1)] compared to late sPE [95.9pM (66.5)] (P=0.046), which suggests a higher pro-coagulant state when PE onset occurs before 34weeks of gestation. CONCLUSION: These pioneer data allow inferring the relevance of FVIIa-AT as a device for early sPE diagnosis. However, the clinical relevance of FVIIa-AT complex surely needs to be fully clarified.

Honey is potentially effective in the treatment of atopic dermatitis: Clinical and mechanistic studies.

INTRODUCTION: As manuka honey (MH) exhibits immunoregulatory and anti-staphylococcal activities, we aimed to investigate if it could be effective in the treatment of atopic dermatitis (AD). METHODS: Adult volunteers with bilateral AD lesions were asked to apply MH on one site overnight for seven consecutive days and leave the contralateral site untreated as possible. Three Item Severity score was used to evaluate the response. Skin swabs were obtained from both sites before and after treatment to investigate the presence of staphylococci and enterotoxin production. In addition, the ability of MH and its methanolic and hexane extracts to down regulate IL4-induced CCL26 protein release from HaCaT cells was evaluated by enzyme linked immunosorbent assay. Also, the ability of MH to modulate calcium ionophore-induced mast cell degranulation was assessed by enzyme immunoassay. RESULTS: In 14 patients, AD lesions significantly improved post MH treatment versus pre-treatment as compared to control lesions. No significant changes in the skin staphylococci were observed after day 7, irrespective of honey treatment. Consistent with the clinical observation, MH significantly down regulated IL4-induced CCL26 release from HaCaT cells in a dose-dependent manner. This effect was partially lost, though remained significant, when methanolic and hexane extracts of MH were utilized. In addition, mast cell degranulation was significantly inhibited following treatment with MH. CONCLUSIONS: MH is potentially effective in the treatment of AD lesions based on both clinical and cellular studies through different mechanisms. This needs to be confirmed by randomized and controlled clinical trials.