Gingival neoplasms: a multicenter collaborative study of 888 patients in Brazil.

BACKGROUND: To evaluate the prevalence and clinicopathological features of a large series of gingival neoplasms in Brazil. MATERIAL AND METHODS:  All gingival benign and malignant neoplasms were retrieved from the records of six Oral Pathology Services in Brazil, during a 41-year period. Clinical and demographic data, clinical diagnosis, and histopathological data were collected from the patients' clinical charts. For statistical analysis, the chi-square, median test of independent samples and the U Mann-Whitney tests were used, considering a significance of 5%. RESULTS:  From 100,026 oral lesions, 888 (0.9%) were gingival neoplasms. There were 496 (55.9%) males, with a mean age of 54.2 years. Most cases (70.3%) were malignant neoplasms. Nodules (46.2%) and ulcers (38.9%) were the most common clinical appearance for benign and malignant neoplasms, respectively. Squamous cell carcinoma (55.6%) was the most common gingival neoplasm, followed by squamous cell papilloma (19.6%). In 69 (11.1%) malignant neoplasms, the lesions were clinically considered to be inflammatory or of infectious origin. Malignant neoplasms were more common in older men, appeared with larger size, and with a time of complaint shorter than benign neoplasms (p<0.001). CONCLUSIONS:  Benign and malignant tumors may appear as nodules in gingival tissue. In addition, malignant neoplasms, especially squamous cell carcinoma, should be considered in the differential diagnosis of persistent single gingival ulcers.

Ameloblastomas mimicking apical periodontitis: a case series.

BACKGROUND: Ameloblastomas are benign odontogenic tumors that can eventually mimic the clinical and radiological features of apical periodontitis. The aim of the present study was to evaluate the clinical, radiological and histological characteristics from a series of ameloblastomas mimicking apical periodontitis diagnosed in a 14-year period. MATERIAL AND METHODS: all cases histologically diagnosed as ameloblastomas from 2005 to 2018 presenting a clinical diagnosis of periapical lesion of endodontic origin were selected for the study. Clinical, radiological and histological characteristics from all cases were tabulated and descriptively and comparatively analyzed. RESULTS: Twenty cases composed the final sample, including 18 solid and 2 unicystic ameloblastomas. Mean age of the affected patients was in the fifth decade with predilection for males (72%). The most common anatomical location was the posterior mandible (55%) and most cases presented a radiolucent unilocular (80%) well-defined (95%) image. Most cases were asymptomatic, but the presence of local swelling and bone cortical rupture were common. CONCLUSIONS: Ameloblastomas mimicking periapical lesions of endodontic origin are mostly diagnosed in adult males as well-defined radiolucent unilocular lesions producing local swelling and bone cortical rupture.

Association between socioeconomic factors and origin of hospital referrals among patients with oral cancer.

BACKGROUND: The Brazilian Unified Health System (SUS) is responsible for offering free assistance to more than 100 million Brazilians, including treatment of oral cancer lesions. Considering that the Brazilian public system aids the most vulnerable population, this study analyzed whether the origin of hospital referrals of patients with oral cancer is associated with socioeconomic factors. MATERIAL AND METHODS: A cross-sectional study was carried out from cancer hospital records of the National Cancer Institute (RHC-INCA), considering the primary locations (C00 to C06) diagnosed between 2016 and 2019. Data on gender, skin color (white and non-white), education (no schooling, incomplete or complete elementary education; high school; incomplete and complete higher education) and origin of referral (SUS and non-SUS) were analyzed by multiple logistic regression (p<0.05). RESULTS: Higher referral rates by the SUS were observed in 2017 (OR=1.27; 95% CI=1.098-1.480) and 2018 (OR=1.28; 95% CI=1.101-1.490); no differences were found between the years 2016 and 2019. Regarding gender, men were 40% more likely to have the SUS as the source of referral (OR=1.40; 95% CI=1.233-1.600). Non-white individuals were 34% more likely to have the SUS as the source of the referral (OR=1.34; 95% CI=1.190-1.512). Illiterate individuals or individuals who only attended elementary school were 6.38 times more likely to be referred by the SUS than individuals with higher education (OR=6.38; 95% CI=5.228-7.796). CONCLUSIONS: It is concluded that the origin of hospital referrals via SUS of patients with oral cancer is associated with socioeconomic factors.

Levels of trace blood elements associated with severe sleep disturbance in maintenance hemodialysis patients.

PURPOSE: Sleep disturbance is frequently observed in patients on maintenance hemodialysis (MHD), and this population usually presents imbalances in trace elements. We investigated the association between blood trace element levels and sleep quality in patients on MHD. METHODS: This cross-sectional and single-center study was performed in September 2019. Patients regularly undergoing hemodialysis for > 3 months at our center were recruited, and demographic, clinical, and laboratory parameters were recorded. The Pittsburgh Sleep Quality Index (PSQI) was applied to define sleep disturbance. Blood trace element (zinc, manganese, copper, selenium, and lead) levels were measured using an inductively coupled plasma mass spectrometer. RESULTS: In total, 121 patients on MHD (male/female = 68:53) were enrolled in the study (mean age 63.7 ± 13.9 years, median dialysis vintage 38.0 [20.0, 60.0] months). According to PSQI, 56 (46%) patients experienced severe sleep disturbance. These patients were characterized by older age, higher serum parathyroid hormone levels, and lower blood selenium levels (all P < 0.05). No significant differences in blood zinc, manganese, copper, and lead levels were observed between groups. Univariate binary logistic regression showed that lower blood selenium levels were associated with severe sleep disturbance (odds ratio = 0.976, 95% confidence interval: 0.954-0.999, P = 0.038). Multivariate analyses also confirmed the results after adjusting for confounding factors. CONCLUSION: Our study indicated an association between lower blood selenium levels and the occurrence of severe sleep disturbances in patients on MHD. However, a prospective study with a larger sample size and assessing the importance of selenium supplementation are needed to confirm the results.

The pesticides use and the risk for head and neck cancer: A review of case-control studies.

BACKGROUND: Tobacco, alcohol consumption, and HPV infection are the most common risk factors for head and neck cancer (HNC). Despite of this, recent evidences are growing on the association between long-term exposure to pesticides and the risk of chronic diseases, including different types of cancer. The present review evaluated in current literature evidence of an association between exposure to pesticides and the occurrence of HNCs. MATERIAL AND METHODS: A literature search of the case-control studies was conducted in the PubMed, Web of science and Cochrane databases. Methodological quality of each study was rated with the Scottish Intercollegiate Guidelines Network (SIGN 50) checklist. RESULTS: One thousand and thirty-five studies were identified and twelve met all criteria and, therefore, considered for quality assessment and data extraction. According to SIGN 50 criteria, six studies received an overall high-quality. All the studies considered of high quality found a positive association between exposure to pesticides and different HNC sites, including larynx, pharynx and nasal cavity. In addition, the increased risk was associated with the frequency of exposure. CONCLUSIONS: Finally, improving pesticide users' awareness of their risks and proper handling, as well as adopting protective measures such as the use of personal protective equipment, appear to be effective in reducing human health damage.

Nonendodontic periapical lesions: a retrospective descriptive study in a Brazilian population.

BACKGROUND: Several nonendodontic diseases can occur in the periapical region, resembling endodontic inflammatory conditions. Therefore, the aim of the present study was to determine the frequency of nonendodontic periapical lesions diagnosed in a Brazilian population. MATERIAL AND METHODS: The files of two Oral Pathology laboratories were reviewed and all cases including at least one clinical diagnosis of endodontic periapical lesions were selected for the study. After initial selection, demographic and clinical data, clinical diagnosis and final diagnosis were reviewed and tabulated. Final diagnosis included endodontic periapical lesions, and benign and malignant nonendodontic periapical lesions. Data were descriptively and comparatively analyzed among the three groups, with a significance level of 5% (p<0.05). RESULTS: Nonendodontic periapical lesions were identified in 208 (19%) out of the 1.125 registries included in the final sample. Benign nonendodontic periapical lesions (200 cases, 18%) were mostly odontogenic keratocysts, ameloblastomas, nasopalatine cysts, dentigerous cysts, glandular odontogenic cysts, and benign fibroosseous lesions. Malignant nonendodontic periapical lesions (8 cases, 1%) included carcinomas, adenocarcinomas, and melanoma. In general, nonendodontic periapical lesions were more common in males and in the posterior mandible (p>0.05). CONCLUSIONS: The frequency of nonendodontic periapical lesions was high and, although the general distribution was similar to the results from other populations, some features were probably associated with the profile of the studied populations and to the methods applied in the present study. Knowledge on differential diagnosis of endodontic and nonendodontic periapical lesions is essential to avoid unnecessary treatments and diagnostic delay in routine dental practice.

Trend of hospitalized cases of oral cancer in Brazil and its relationship with oral health coverage in public health system between 2009 and 2017.

BACKGROUND: This study aimed to analyze the trend in the number of hospitalized cases of oral cancer in Brazil, according to the coverage of oral health services in public health system, and also investigate the influence of healthcare and clinical characteristics on the severity of oral cancer cases. MATERIAL AND METHODS: This retrospective study considered the period between 2009 and 2017. Data from the Hospital Registry of Cancer from the National Cancer Institute were used, considering the primary locations C00 to C06. Detailed information including sex, age, alcohol and tobacco use, year of first consultation, and the clinical stage of the cases were also collected. The frequency of hospitalized cases was correlated with the coverage of Primary Care Oral Health Teams (ESB) and the number of Dental Specialty Centers (CEO). It was also estimated the chance of advanced oral cancer cases, according to healthcare and clinical characteristics. Data were analyzed using Tweedie's multiple regression and multiple binary logistic regression (α<0.05). RESULTS: There was an increasing trend in the number of hospitalized cases of oral cancer in Brazil between 2009 and 2017 (B=0.043, p<0.001, PR=1.044). The increase in ESB coverage was associated with small increase in the number of hospitalized cases of oral cancer (B=0.001, p=0.003, PR=1.001). The increase in the number of CEO was associated with decrease in the number of hospitalized cases of oral cancer (B=-0.085, p<0.001, PR =0.918). The increase of ESB (OR=0.998) and CEO (OR=0.974) contributed for reducing the number of stage IV cases, whilst the history of alcohol and tobacco use (OR=1.574) was associated with an increase in the number of stage IV cases. CONCLUSIONS: Although an increasing trend was detected, the expansion of the public health system reduced the number of hospitalized cases and the frequency of advanced oral cancer cases in Brazil.

Association between time to treatment and functional outcomes according to the Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score in endovascular stroke therapy.

BACKGROUND AND PURPOSE: The rate at which the chance of a good outcome of endovascular stroke therapy (EVT) decays with time when eligible patients are selected by baseline diffusion-weighted magnetic resonance imaging (DWI-MRI) and whether ischaemic core size affects this rate remain to be investigated. METHODS: This study analyses a prospective multicentre registry of stroke patients treated with EVT based on pretreatment DWI-MRI that was categorized into three groups: small [Diffusion-Weighted Imaging Alberta Stroke Program Early Computed Tomography Score (DWI-ASPECTS)] (8-10), moderate (5-7) and large (<5) cores. The main outcome was a good outcome at 90 days (modified Rankin Scale 0-2). The interaction between onset-to-groin puncture time (OTP) and DWI-ASPECTS categories regarding functional outcomes was investigated. RESULTS: Ultimately, 985 patients (age 69 ± 11 years; male 55%) were analysed. Potential interaction effects between the DWI-ASPECTS categories and OTP on a good outcome at 90 days were observed (Pinteraction  = 0.06). Every 60-min delay in OTP was associated with a 16% reduced likelihood of a good outcome at 90 days amongst patients with large cores, although no associations were observed amongst patients with small to moderate cores. Interestingly, the adjusted rates of a good outcome at 90 days steeply declined between 65 and 213 min of OTP and then remained smooth throughout 24 h of OTP (Pnonlinearity  = 0.15). CONCLUSIONS: Our study showed that the probability of a good outcome after EVT nonlinearly decreased, with a steeper decline at earlier OTP than at later OTP. Discrepant effects of OTP on functional outcomes by baseline DWI-ASPECTS categories were observed. Thus, different strategies for EVT based on time and ischaemic core size are warranted.

Awareness on oral cancer among patients attending dental school clinics in Brazil.

BACKGROUND: Oral cancer is considered a public health problem worldwide. Dental schools may play an important role in educating patients about oral cancer. This study aimed at evaluating the knowledge of patients attending clinics at two dental schools in Brazil. MATERIAL AND METHODS: From March 2017 to April 2017, 251 patients who were attending clinics at two dental schools in Recife, Brazil, were included in the study. Patients were contacted in the waiting rooms of the clinic. Each participant completed a self-administered questionnaire, which consists of 21 questions, including socio-demographic and specific information on the disease. Data were analyzed using descriptive statistics, and a chi-square test (with a 5% significance level) was used to assess the correlation between the variables, education and family income and other variables. RESULTS: Most participants were women (64.9%) with a mean age of 42.72 years. Most participants were knowledgeable about oral cancer and identified tobacco use (48.6%), alcohol consumption (25.1%), and solar radiation (12%) as the primary risk factors for the disease. Only 36.7% of the participants reported having received counselling on oral cancer, of which 18.3% received the information from a dentist. All patients with an income higher than six minimum wages were aware about oral cancer (p = 0.001). CONCLUSIONS: These findings emphasize the importance of educational programs in dental schools as well providing integrated services for patients seeking care at school clinics, including population's awareness on oral cancer.

Quality of information about oral cancer in Brazilian Portuguese available on Google, Youtube, and Instagram.

BACKGROUND: To evaluate the quality of oral cancer information in Brazilian Portuguese on Google, YouTube, and Instagram. MATERIAL AND METHODS: The first 100 links of each platform characterized the initial sample. The websites and Instagram were evaluated using the JAMA benchmarks, the Discern instrument, and the Flesch readability index (Flesch Reading Ease). The existence of Health on the Net (HON) code was also registered on websites. The usefulness of each video on YouTube was classified as not useful, slightly useful, moderately useful, or very useful. RESULTS: Thirty-four websites, 39 Instagram posts, and 57 videos were evaluated, of which 18 (33.3%) websites and 19 (48.7%) Instagram posts covered only 2 of the 4 JAMA benchmarks. For the Discern instrument, 20 (37%) and 18 (33.3%) websites exhibited low and moderate reliability, respectively, while 26 (66.7%) Instagram posts were of low confidence. The level of intelligibility of both websites and Instagram was difficult. Only three websites exhibited the HONcode. Forty-one (71.9%) videos on YouTube were moderately useful. CONCLUSIONS: Information on oral cancer on the Internet in Brazilian Portuguese is of low quality. Thus, educational and governmental institutions have a responsibility to produce and indicate reliable sources of information for the population.

Job satisfaction of staff in agencies for disease prevention and control in Hainan Province, China.

This study done in Hainan from March 2017 to June aimed to assess job satisfaction status and influencing factors among the staff of agencies for disease prevention and control in Hainan Province. A questionnaire survey was administered to some staff members at 6 centers for disease control and prevention in Hainan Province, job satisfaction in the questionnaire was rated on a 5-points Likert scale (totally agree, agree, not sure, disagree, totally disagree). The average score of job satisfaction for the six centers was 3.35±0.77, which was relatively low. According to the Wilcoxon rank-sum test, job satisfaction showed significant differences among different job titles (P <0.05). Logistic regression showed that the factors influencing job satisfaction were personal development space, rulesand regulations in CDC, personal safety, public health system, and workload. The factors influencing the staff's satisfaction are personal development space, rules and regulations in CDC, personal safety, public health system and workload.

Construction of biocompatible bovine serum albumin nanoparticles composed of nano graphene oxide and AIEgen for dual-mode phototherapy bacteriostatic and bacterial tracking.

BACKGROUND: Efficient and highly controllable antibacterial effect, as well as good biocompatibility are required for antibacterial materials to overcome multi-drug resistance in bacteria. Herein, nano graphene oxide (NGO)-based near-infrared (NIR) photothermal antibacterial materials was schemed to complex with biocompatible bovine serum albumin (BSA) and aggregation-induced emission fluorogen (AIEgen) with daylight-stimulated ROS-producing property for dual-mode phototherapy in the treatment of antibiotic resistance bacteria. RESULTS: Upon co-irradiation of daylight and NIR laser, NGO-BSA-AIE nanoparticles (NPs) showed superiorly antibacterial effect (more than 99%) both against amoxicillin (AMO)-resistant Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) by comparison with sing-model phototherapy. Meanwhile, the NGO-BSA-AIE NPs displayed prominent stability and excellently controllable biocompatibility. More importantly, under daylight irradiation, the AIEgen not only produced plentiful ROS for killing bacteria, but also presented fluorescence image for tracking bacteria. CONCLUSIONS: Hence, the designed system provided tempting strategy of employing light as impetus for tracking bacterial distribution and photothermal/photodynamic synergistic treatment of antibiotic resistance antibacterial.

[XP gene polymorphisms and haplotypes with genetic susceptibility to lung cancer].

OBJECTIVE: To investigate the association of DNA repair gene XPB, XPD and XPG gene polymorphisms and haplotypes with genetic susceptibility to lung cancer. METHODS: A case-control study was conducted, the case group was 100 lung cancer patients in Hainan Province, while the control group was 100 cases of respiratory diseases in Hainan Province. The polymorphism of XPB gene rs4150441 and rs4150434 loci, the polymorphism of the rs171140 and rs11878544 loci of the XPD gene, the XPG gene rs4771436, and the polymorphism of the rs2094258 and rs17655 loci were detected by mass spectrometry. Halopview software was used to investigate the association between XP gene polymorphism and haplotype and genetic susceptibility to lung cancer. RESULTS: The experimental result showed that the rs4150434 locus of XPB gene, the rs4771436 locus of XPG gene and the rs2094258 locus of XPG gene were associated with the genetic susceptibility of lung cancer(P < 0. 05). Among the rs4150434 loci of XPB gene, the susceptibility of individuals carrying heterozygous GA to lung cancer was 2. 071 times than wild type GG(OR = 2. 071, 95% CI = 1. 055-4. 067). The susceptibility of individuals with mutant AA to lung cancer was 2. 535 times than wild type GG(OR =2. 535, 95%CI = 1. 063-6. 044). In the rs4771436 locus of XPG gene, the susceptibility of individuals carrying mutant GG to lung cancer was 2. 494 times than wild type TT(OR = 2. 494, 95% CI = 1. 038-5. 992). In the rs2094258 locus of XPG gene, the susceptibility of individuals carrying mutant AA to lung cancer was 3. 020 times than wild type GG(OR = 3. 020, 95%CI = 1. 015-8. 980). As haplotype result show, compared with GG haplotypes of rs4150441-rs4150434 loci in XPB gene, the risk of lung cancer in GA haplotype was 3. 643 times than GG haplotype(OR = 3. 643, 95% CI = 1. 113-11. 921). Compared with GTC haplotypes of rs2094258-rs4771436-rs17655 loci in XPG gene, the risk of lung cancer in ATC haplotype was 3. 800 times than GTC haplotype(OR = 3. 800, 95%CI = 1. 073-13. 459). CONCLUSION: XPB rs4150434, XPG rs4771436, XPG rs2094258 locus polymorphism and haplotype are associated with the genetic susceptibility to lung cancer.

Exposure to beta-cypermethrin impairs the reproductive function of female mice.

This study aimed to investigate the effects of beta-cypermethrin (ß-CYP) on female reproductive function and examine the morphology of the uterine endometrium and follicular development. The results found that the rate of successful pregnancy in the ß-CYP-treated groups significantly decreased. The levels of serum E2 and FSH were significantly increased in the ß-CYP-treated groups. The concentrations of serum P and LH were significantly decreased in the ß-CYP-treated groups. The uterine endometrium was damaged and the endometrial pinopode was markedly inhibited. In addition, the total number of follicles of all types was significantly lower in the medium- and high-dose ß-CYP-treated groups. These results suggest that ß-CYP significantly affected the reproductive function of female mice. ß-CYP may have significantly decreased the fertility of female mice by disturbing the reproductive hormone concentrations and inhibiting the development of the endometrium and the endometrial pinopode.

[Occupational characteristics and clinical manifestations of 245 cases of occupational brucellosis].

Objective: To analyse epidemiological, clinical characteristics and laboratory examination results of 245 occupational brucellosis form 2008 to 2018, which providing theoretical basis for prevention and control of occupational brucellosis. Methods: Based on the China Center for Disease Control and Prevention Information System, a database of occupational brucellosis cases in HunlunBuir from January 2008 to July 2018 was established. The Epidemiological characteristics, Clinical manifestation, laboratory examination of 245 occupational brucellosis and 359 without occupational brucellosis were comparatively analyzed about the same period. Results: Among the 245 patients, 219 were males, 254 in 359, malese were significantly higher than control group (χ(2)=21.331, P<0.05) . Fever, fatigue, hyperhidrosis and splenomegaly are common in patients with occupational brucellosis and non occupational brucellosis. Arthralgia (54.3%/44.8%) and CRP (81.2%/71.3%) were significantly also higher than control group (χ(2)=5.193, P<0.05; χ(2)=7.704, P<0.05) Fever, hyperhidrosis, fatigue and splenomegaly were common clinical manifestation and signs in the two groups. Brucellosis can cause a variety of complications, including osteoarticular hematological system and hepatic involvement, some patients with multiple system damage. Conclusion: The incidence of occupational brucellosis in HulunBuir is concentrated in agriculture and animal husbandry. Veterinarians are the main occupational groups, Occupational health interventions should be strengthened for key occupational hazards, regular occupational health examination, avoid chronic brucellosis and protect the health of key occupational groups.

Immunologic regulatory effects of human umbilical cord blood-derived mesenchymal stem cells in a murine ovalbumin asthma model.

BACKGROUND: Mesenchymal stem cells (MSCs) have multiple immunomodulatory properties and hold therapeutic potential for inflammatory diseases. However, the therapeutic and immunologic effects of human umbilical cord blood-derived MSCs (huMSCs) remain largely unexamined for asthma. OBJECTIVE: This study was to investigate the immunomodulatory properties of huMSCs in an ovalbumin (OVA)-induced murine asthma model. METHODS: Mice were injected intraperitoneally with OVA and an aluminium hydroxide adjuvant. huMSCs were administered via the tail vein (5×105 cells/100 uL) to female BALB/c mice prior to the initial OVA challenge. The effects of huMSCs were assessed by investigating airway hyperresponsiveness, histological changes, inflammatory cell numbers, serum allergen-specific antibodies, cytokine production in spleen, lung tissue, and bronchoalveolar lavage (BAL) fluid as well as expansion of regulatory T cells. RESULTS: Administration of huMSCs significantly reduced methacholine bronchial hyperresponsiveness and eosinophil counts in BAL cells. Similarly, there was a significant decrease in serum OVA-specific IgE and IgG1 levels along with Th2 cytokine production (IL-4, IL-5, and IL-13) in the lung and spleen tissues, whereas increased percentage of regulatory T cells was observed after treatment with huMSCs. CONCLUSIONS: Our results suggest that huMSC treatment reduces OVA-induced allergic inflammation, which could be mediated by regulatory T cells.

Polyplex Micelle with pH-Responsive PEG Detachment and Functional Tetraphenylene Incorporation to Promote Systemic Gene Expression.

Tetraphenylene (TPE), characterized as a lipophilic and aggregation-induced-emissive fluorophore, was used to incorporate into an electrostatic self-assembled polyethylenimine-poly(ethylene glycol) (PEI-PEG)/plasmid DNA (pDNA) complexed micelle. The hydrophobic character of TPE appeared to drive a higher degree of condensation of the pDNA payload, which consequently resulted in not only strengthened colloidal stability of the constructed polyplex micelle but also improved biocompatibility by virtue of the elevated PEG crowdedness owing to the TPE-induced collapse of pDNA. These beneficial consequences potentially permitted a larger number of polyplex micelles to be internalized into the cells. PEG segments were designed to enable selective detachment from polyplex micelles in acidic milieu, e.g., the tumor microenvironment, and intracellular endosome compartment, based on the strategic arrangement of acid-responsive cleavable linkage between PEG and PEI. Upon PEG detachment, the exposure of cationic PEI/TPE polyplex was allowed to directly interact with the cell membrane, endosome membrane, and charged intracellular species, thus promoting cell internalization, endosome escape, and the release of the pDNA payload. Of note, this association of cationic PEI/TPE polyplex with the endosomal membrane could be further facilitated with the aid of lipophilic TPE, thereby eliciting pronounced destabilization potency to the endosome membrane and exerting an endosomal escape function. Eventually, the proposed system of these facile strategies, including responsive PEG detachment and functional TPE incorporation, was proven to provide efficient gene expression in the targeted tumors with an appreciable safety profile via systemic administration.

The sphingosine-1-phosphate receptor 1 binding molecule FTY720 inhibits osteoclast formation in rats with ligature-induced periodontitis.

BACKGROUND AND OBJECTIVE: Osteoclast precursors (OPs) re-migrate from the bone surface into blood vessels through sphingosine-1-phosphate receptor 1 (S1PR1) expression. T cells also express S1PR1, mediating their migration from the lymph nodes into blood vessels. OP and T-cell migration are one of the sequential steps related to osteoclast formation. To characterize the role of S1PR1 in osteoclast formation induced by periodontitis, we investigated the effect of S1PR1-binding molecule FTY720 (FTY) on the number of OPs and T cells in periodontal tissue and peripheral blood of rats with ligature-induced periodontitis. MATERIAL AND METHODS: Rats were divided into four groups; control (Con), FTY, periodontitis (Peri), and periodontitis+FTY (Peri+FTY) groups. Ligatures were placed around the first molars in the left and right mandibles. The rats were intraperitoneally injected with vehicle or 3 mg/kg FTY daily until they were killed. The number of osteoclasts and cluster of differentiation (CD)11b, CD3 and receptor activator of NF-κB ligand (RANKL)-positive cells in first molar furcation were counted by tartrate-resistant acid phosphatase or immunohistochemistry staining. The number of CD11b- and CD3-positive cells in peripheral blood was estimated by flow cytometry. RESULTS: The number of osteoclasts in the Peri group was higher than Con, Peri+FTY and FTY groups (p < 0.05) and CD11b, CD3 and RANKL-positive cells were also higher in the Peri group than other groups in furcation (p < 0.05). While CD11b-positive cells in furcation of the Peri+FTY group were lower than the Peri group (p < 0.05), they were higher in peripheral blood (p < 0.05). Dissimilar to CD11b-positive cells, CD3-positive cells in the Peri+FTY group were lower in peripheral blood as well as furcation than the Peri group (p < 0.05). RANKL-positive cells in furcation of the Peri+FTY group were also lower than Peri group (p < 0.05). CONCLUSION: These results indicate that FTY may facilitate re-migration of OPs from the alveolar bone surface into blood vessels, blocking T-cell migration from the lymph nodes into blood vessels and subsequently reducing osteoclast formation induced by periodontitis. This suggests that S1PR1-S1P binding may play a role in osteoclast formation of periodontitis by modulating OP and T-cell migration.

Charge and aggregation pattern govern the interaction of plasticins with LPS monolayers mimicking the external leaflet of the outer membrane of Gram-negative bacteria.

Bacterial resistance to antibiotics has become today a major public health issue. In the development of new anti-infectious therapies, antimicrobial peptides appear as promising candidates. However, their mechanisms of action against bacterial membranes are still poorly understood. We describe for the first time the interaction and penetration of plasticins into lipid monolayers and bilayers modeling the two leaflets of the asymmetrical outer membrane of Gram-negative bacteria. The lipid composition of these monolayers mimics that of each leaflet: mixtures of LPS Re 595 mutant and wild type S-form from Salmonella enterica for the external leaflet, and SOPE/SOPG/cardiolipin (80/15/5) for the inner one. The analysis of the interfacial behavior of native (PTCDA1) and modified (PTCDA1-KF) antimicrobial plasticins showed that PTCDA1-KF exhibited better surface properties than its unmodified counterpart. Both peptides could penetrate into the model monolayers at concentrations higher than 0.1 µM. The penetration was particularly enhanced for PTCDA1-KF into the mixed LPS monolayer, due to attractive electrostatic interactions. Grazing X-ray diffraction and atomic force microscopy studies revealed the changes in LPS monolayers organization upon peptide insertion. The interaction of plasticins with liposomes was also monitored by light scattering and circular dichroism techniques. Only the cationic plasticin achieved full disaggregation and structuration in α helices, whereas the native one remained aggregated and unstructured. The main steps of the penetration mechanism of the two plasticins into lipid models of the external leaflet of the outer membrane of Gram-negative bacteria have been established.

Hepatitis C virus long-term persistence in peripheral blood mononuclear cells in patients with haemophilia. Detection of occult genotype 1.

Peripheral blood mononuclear cells (PBMC) from chronic hepatitis C virus-infected persons can harbour viral variants that are not detected in plasma samples. We explored the presence and persistence of HCV genotypes in plasma and PBMC cultures from 25 HCV-monoinfected and 25 HIV/HCV-coinfected patients with haemophilia. Cell cultures were performed at different time points between 1993 and 2010-2011, and the HCV genome was examined in culture supernatants. Sequential plasma samples were studied during the same time period. Analysing sequential plasma samples, 21% of patients had mixed-genotype infections, while 50% had mixed infections determined from PBMC culture supernatants. HIV coinfection was significantly associated with the presence of mixed infections (OR = 4.57, P = 0.02; 95% CI = 1.38-15.1). In our previous study, genotype 1 was found in 72% of 288 patients of this cohort. Similar results were obtained with the sequential plasma samples included in this study, 69% had genotype 1. However, when taking into account plasma samples and the results from PBMC supernatants, genotype 1 was identified in 94% of the population. The PBMC-associated variants persisted for 10 years in some subjects, emphasizing their role as long-term reservoirs. The presence of genotype 1 in PBMC may be associated with therapeutic failure and should not be disregarded when treating haemophilic patients who have been infected by contaminated factor concentrates. The clinical implications of persistent lymphotropic HCV variants deserve further examination among multiple exposed groups of HCV-infected patients.