Efeitos da fibrose cística sobre o microbioma bucal e o proteoma salivar / Effects of cystic fibrosis on oral microbiome and salivary proteome

A Fibrose Cística (FC) é uma doença genética de elevada prevalência global e que causa função anormal das glândulas exócrinas. As alterações nas funções das glândulas salivares podem impactar a saúde bucal que por sua vez podem influenciar a saúde geral. A boca pode representar um reservatório microbiano de potenciais patógenos e colonizadores das vias aéreas, causando infecções crônicas pulmonares. O objetivo deste estudo foi avaliar os impactos da FC na cavidade bucal, saliva e microbioma bucal. Foram incluídos no estudo 50 pacientes com diagnóstico de FC com idades de 3 a 20 anos, divididos em 2 grupos de acordo com o grau de severidade da doença determinado pelo escore de Shwachman-Kulczycki: G1 (baixa severidade) e G2 (alta severidade). Foi também incluído grupo controle pareado ao grupo de estudo quanto ao gênero e idade (G3, n=50). A presença de lesões de cárie foi avaliada. O impacto da FC sobre a saúde bucal foi avaliado por questionário preenchido pelos pais ou responsáveis. Amostra de saliva estimulada foi coletada de todos os pacientes. O microbioma bucal foi avaliado por Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS) e metodologias de cultivo, para análise da microbiota potencialmente oportunista e cariogênica. Realizouse ainda a análise proteômica da saliva e quantificação de imunoglobulinas salivares. Os resultados foram analisados e, de acordo com a distribuição dos dados e avaliação desejada, foram aplicados os testes estatísticos apropriados, sendo adotado o nível de significância de 5%. O questionário aplicado apontou que os pais consideraram que a saúde bucal não impacta negativamente a saúde geral dos seus filhos em todos os grupos estudados Os grupos de pacientes com FC apresentaram menores índices de Ceo-d, CPO-D, taxa de fluxo salivar e pH inicial em relação ao grupo controle. As contagens de estafilococos e leveduras foram significativamente mais elevadas nos grupos FC. Todos os isolados fúngicos foram suscetíveis aos antifúngicos testados. Alta incidência de resistência foi observada dentre as cepas bacterianas. Os níveis de IgA foram mais altos nos grupos com FC em relação ao controle. Pseudomonas aeruginosa foi detectada apenas nos grupos com FC. A análise proteômica identificou 7 potenciais biomarcadores para a fibrose cística. Conclui-se que o monitoramento do microbioma oral de pacientes com fibrose cística pode ser uma ferramenta importante na prevenção da colonização pulmonar por potenciais patógenos. O estudo de biomarcadores salivares pode contribuir para o desenvolvimento de novos métodos de diagnóstico alternativos ao teste do suor para a fibrose cística(AU)

Cystic Fibrosis (CF) is a genetic disease with high global prevalence that causes abnormal function of the exocrine glands. The functional alterations of salivary glands and saliva can impact the oral health and influence general health. Oral cavity may represent a microbial reservoir of potential pathogens that can colonize the airways and cause chronic pulmonary infections. The aim of this study is to evaluate the impact of cystic fibrosis on the oral cavity, saliva and oral microbiome. Fifty CF patients aged from 3 to 20 years were divided into two groups according to the disease severity determined by the Shwachman-Kulczycki score: G1 (low severity) and G2 (high severity). Also, age and gender paired control group was included in the study (G3, n = 50). The occurrence of caries was evaluated. The impact of CF on oral health was evaluated by a questionnaire filled by parents or responsible person. Stimulated whole saliva (WS) samples were collected from all patients. The oral microbiome was analyzed by Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS) and by microbiological culture methodologies to evaluate the potential opportunistic and cariogenic microbiota. The proteomic analysis of saliva and quantification of salivary immunoglobulins were carried out. Statistical analysis was performed according to the normality of the data at a significance level of 5%. The applied questionnaire pointed out that oral health did not impact systemic health negatively, according to the parents in all groups. The groups of patients with CF had lower rates of dmft, DMFT, salivary flow rate and initial pH in comparison to the control group. The counts of staphylococcal and yeast from CF groups were significant higher than the controls. All fungal isolates were susceptible to the antifungal agents. Higher incidence of bacterial resistance was observed. The IgA levels were higher in both CF groups than in the control group. Pseudomonas aeruginosa were detected only in the CF groups. The proteomic analysis identified 7 potential biomarkers for cystic fibrosis. The effects of CF in saliva and oral microbiome must be considered to establishment of therapeutic and preventives multidisciplinary protocols aiming overall health and quality of life of these patients. In conclusion, monitoring the oral microbiome of CF patients may be an important tool in the prevention of pulmonary colonization by potential pathogens. The study of salivary biomarkers may contribute to the development of new diagnostics methods alternative to sweat test for CF(AU)

Risk of serious infection in patients with rheumatoid arthritis-associated interstitial lung disease.

The objective of this study is to assess the occurrence of and risk factors for serious infections in rheumatoid arthritis (RA)-associated interstitial lung disease (ILD). All patients with RA-ILD (ACR 1987 criteria for RA) seen at a single center from 1998 to 2014 were identified and manually screened for study inclusion. Follow-up data were abstracted until death or December 31, 2015. Serious infection was defined as requiring antimicrobial therapy and hospitalization. Risk of infection was analyzed by person-year (py) methods using time-dependent covariates started when the medication was first used and stopped 30 days after the medication was discontinued. Of the 181 included patients, 87 (48 %) were female. The mean age at ILD diagnosis was 67.4 (±9.9) years, and median follow-up time was 3.1 (range: 0.01 to 14.8) years. Higher infection rates were observed during the first year after ILD diagnosis (14.1 per 100 py) than subsequently (5.7 per 100 py; p = 0.001). Pneumonia was the most common (3.9 per 100 py). Overall infection risk was higher in organizing pneumonia (OP) (27.1 per 100 py) than usual interstitial pneumonia (7.7 per 100 py) or non-specific interstitial pneumonia (5.5 per 100 py) (p < 0.001). The highest infection rate observed was with a daily prednisone use >10 mg per day (15.4 per 100 py). Patients with RA-ILD are at risk of serious infection. Prednisone use >10 mg per day was associated with higher rates of infection. Immunosuppressive drug use governed by concern for risk of infection in patients with ILD resulting in channeling bias cannot be excluded.

Systemically active human opiorphin is a potent yet non-addictive analgesic without drug tolerance effects.

Human opiorphin QRFSR-peptide protects enkephalins from degradation by human neutral endopeptidase (hNEP) and aminopeptidase-N (hAP-N) and inhibits pain perception in a behavioral model of mechanical acute pain (1). Here, using two other pain rat models, the tail-flick and the formalin tests, we assess the potency and duration of the antinociceptive action of opiorphin with reference to morphine. The occurrence of adverse effects with emphasis on the side-effect profile at equi-analgesic doses was compared. We demonstrate that opiorphin elicits minimal adverse morphine-associated effects, at doses (1-2 mg/kg, i.v.) that produce a comparable analgesic potency in both spinally controlled thermal-induced acute and peripheral chemical-induced tonic nociception. The analgesic response induced by opiorphin in the formalin-induced pain model preferentially requires activation of endogenous mu-opioid pathways. However, in contrast to exogenous mu-opioid agonists such as morphine, opiorphin, does not develop significant abuse liability or antinociceptive drug tolerance after subchronic treatment. In addition, anti-peristaltism was not observed. We conclude that opiorphin, by inhibiting the destruction of endogenous enkephalins, which are released according to the painful stimulus, activates restricted opioid pathways specifically involved in pain control, thus contributing to a greater balance between analgesia and side-effects than found with morphine. Therefore, opiorphin could give rise to new analgesics endowed with potencies similar to morphine but with fewer adverse effects than opioid agonists. Its chemical optimization, to generate functional derivatives endowed with better bioavailability properties than the native peptide, could lead to a potent class of physiological type analgesics.

Structural biology of allergens from stinging and biting insects.

PURPOSE OF REVIEW: Modern techniques in genomic and protein research are applied to the study of stinging and biting insect allergens. RECENT FINDINGS: Three-dimensional structures of additional insect venom and salivary allergens have been determined. An approach to determining B-cell epitopes has been used for hyaluronidase. A number of new venom and salivary allergens have been characterized. The structures and significance of several insect allergens have been updated. Investigations continue into distinguishing venom crossreactivity from multiple sensitization. Further studies are clarifying the significance of carbohydrate epitopes. Genomic and proteomic techniques are being used in the investigation of proteins and peptides in insect venom and saliva. SUMMARY: The nature of venom crossreactivity and the B-cell and T-cell epitope structures of insect venom and salivary allergens are beginning to be elucidated.

Advances in mosquito allergy.

PURPOSE OF REVIEW: Allergic reactions, including severe local and systemic reactions to mosquito bites, are immunological in nature, and involve immunoglobulin E, immunoglobulin G, and T-lymphocyte-mediated hypersensitivities in response to allergens in mosquito saliva. Naturally acquired desensitization to mosquito saliva may occur during childhood or during long-term exposure to mosquitoes. Due to the lack of availability of mosquito salivary preparations for use in skin tests and in-vitro tests, allergic reactions to mosquito bites are under diagnosed and under treated. RECENT FINDINGS: Recombinant saliva allergens with biological activity are being developed. Recombinant Aedes aegypti salivary allergen rAed a 2 has been expressed, purified, characterized and used in in-vitro diagnosis of mosquito allergy. Mosquito saliva-induced non-immunoglobulin E-mediated skin mast cell degranulation was found to induce macrophage-inflammatory protein 2 in the skin and interleukin-10 in draining lymph nodes. SUMMARY: In this review, we discuss the allergic reactions to mosquito salivary allergens, the immune mechanisms involved, natural desensitization and immunotherapy with mosquito extracts, characteristics of salivary allergens and their recombinant forms, and prevention and treatment of allergic reactions to mosquito bites. Eventually, recombinant salivary allergens will significantly improve the diagnosis of mosquito allergy, and will also improve specific immunotherapy for patients with systemic reactions to mosquito bites.

Abducens nerve palsy following a tick bite: a case report.

Neuromuscular paralysis caused by salivary proteins of ticks is a well-known complication after tick bites in Australia, North America, and South Africa. Symptoms may include general weakness, difficulty walking, ascending paralysis, and bulbar paralysis with diplopia, culminating in respiratory failure. In Europe, toxin-mediated paralysis has rarely been noted. We report a case of cranial nerve paralysis with delayed onset after a tick bite in northern Germany.

[Itching caused by insects]. / Prurigo por insecto.

Papular urticaria is a cutaneous manifestation caused by the sensitization to salivary antigens inoculated in insect bites. It is mainly seen in children. Clinical, aetiological, epidemiological, histophatological and immunological features are considered, as well as prevention and treatment aspects.

Evoluçäo pós-natal de glândula submandibular de animais nascidos de ratas injetadas com Parotin: estudo morfológico / Submandibular gland postnatal evolution of animals born from female rats injected with Parotin: morphological study

As glândulas submandibulares de 48 animais nascidos de ratas injetadas com Parotin foram estudadas morfologicamente, tendo sido constatado que, em relaçäo aos animais nascidos de ratas-controle, tais glândulas exibiram hiperplastia e morfodiferenciaçäo mais precoce, principalmente naqueles nascidos de ratas injetadas com 4 doses de droga

Administraçäo de Parotin em ratas prenhes e seu efeito sobre o peso ponderal dos filhotes / Parotin administration in pregnant rats and its effect on the ponderal weight of the youngs

O peso corporal de 48 filhotes nascidos de ratas injetadas com Parotin apresentou-se aumentado em relaçäo a 12 animais nascidos de ratas controle; sendo que aos 5 e 15 dias referido ganho de peso foi estatisticamente significativo. Igualmente os pesos absoluto e relativo da glândula submandibular apresentaram diferenças estatisticamente significativas aos 5 e 15 dias de vida