Antimicrobial efficacy of in vitro and ex vivo photodynamic therapy using porphyrins against Moraxella spp. isolated from bovine keratoconjunctivitis.

Infectious bovine keratoconjunctivitis (IBK) is an ocular disease affecting bovine herds worldwide, and it causes significant economic loss. The etiologic agent of IBK is considered to be Moraxella bovis, but M. ovis and M. bovoculi are frequently recovered of animals presenting clinical signs of IBK. The therapeutic measures available for its control have limited efficacy. Antimicrobial photodynamic therapy (aPDT) using porphyrins as photosensitizing molecules is an alternative method that can be used to reduce microbial growth. We evaluated the antibacterial activity of aPDT using two water-soluble tetra-cationic porphyrins (H2TMeP and ZnTMeP) against 22 clinical isolates and standard strains of Moraxella spp. in vitro and in an ex vivo model. For the in vitro assay, 4.0 µM of porphyrin was incubated with approximately 1.0 × 104 CFU/mL of each Moraxella sp. isolate and exposed to artificial light for 0, 2.5, 5, and 7.5 min. Next, 50 µL of this solution was plated and incubated for 24 h until CFU measurement. For the ex vivo assay, corneas excised from the eyeballs of slaughtered cattle were irrigated with Moraxella spp. culture, followed by the addition of zinc(II) porphyrin ZnTMeP (4.0 µM). The corneal samples were irradiated for 0, 7.5, and 30 min, followed by swab collection, plating, and CFU count. The results demonstrated the in vitro inactivation of the strains and clinical isolates of Moraxella spp. after 2.5 min of irradiation using ZnTMeP, reaching complete inactivation until 7.5 min. In the ex vivo experiment, the use of ZnTMeP resulted in the most significant reduction in bacterial concentration after 30 min of irradiation. These results encourage future in vivo experiments to investigate the role of metalloporphyrin ZnTMeP in the inactivation of Moraxella spp. isolates causing IBK.

The global prevalence of apical periodontitis: a systematic review and meta-analysis.

BACKGROUND: Apical periodontitis (AP) frequently presents as a chronic asymptomatic disease. To arrive at a true diagnosis, in addition to the clinical examination, it is mandatory to undertake radiographic examinations such as periapical or panoramic radiographs, or cone-beam computed tomography (CBCT). Thus, the worldwide burden of AP is probably underestimated or unknown. Previous systematic reviews attempted to estimate the prevalence of AP, but none have investigated which factors may influence its prevalence worldwide. OBJECTIVES: To assess: (i) the prevalence of AP in the population worldwide, as well as the frequency of AP in all teeth, nontreated teeth and root filled teeth; (ii) which factors can modify the prevalence of AP. METHODS: A search was conducted in the PubMed-MEDLINE, EMBASE, Cochrane-CENTRAL, LILACS, Google scholar and OpenGrey databases, followed by hand searches, until September 2019. Cross-sectional, case-control and cohort studies reporting the prevalence of AP in humans, using panoramic or periapical radiograph or CBCT as image methods were included. No language restriction was applied. An adaptation of the Newcastle-Ottawa Scale was used to evaluate the quality of the studies. A meta-analysis was performed to determine the pooled prevalence of AP at the individual level. Secondary outcomes were the frequency of AP in all teeth, nontreated teeth and rootfilled teeth. Subgroup analyses using random-effect models were carried out to analyse the influence of explanatory covariables on the outcome. RESULTS: The search strategy identified 6670 articles, and 114 studies were included in the meta-analysis, providing data from 34 668 individuals and 639 357 teeth. The prevalence of AP was 52% at the individual level (95% CI 42%-56%, I2  = 97.8%) and 5% at the tooth level (95% CI 4%-6%; I2  = 99.5%). The frequency of AP in root-filled teeth and nontreated teeth was 39% (95% CI 36%-43%; I2  = 98.5%) and 3% (95% CI 2%-3%; I2  = 99.3%), respectively. The prevalence of AP was greater in samples from dental care services (DCS; 57%; 95% CI 52%-62%; I2  = 97.8%) and hospitals (51%; 95% CI 40%-63%; I2  = 95.9%) than in those from the general population (GP; 40%; 95% CI 33%-46%; I2  = 96.5%); it was also greater in people with a systemic condition (63%; 95% CI 56%-69%, I2  = 89.7%) compared to healthy individuals (48%; 95% CI 43%-53%; I2  = 98.3%). DISCUSSION: The subgroup analyses identified explanatory factors related to the variability in the prevalence of AP. However, the high clinical heterogeneity and high risk of bias across the primary studies indicate that the findings must be interpreted with caution. CONCLUSIONS: Half of the adult population worldwide have at least one tooth with apical periodontitis. The prevalence of AP is greater in samples from the dental care services, but it is also high amongst community representative samples from the general population. The present findings should bring the attention of health policymakers, medical and dental communities to the hidden burden of endodontic disease in the population worldwide.

The toxin BjussuLAAO-II induces oxidative stress and DNA damage, upregulates the inflammatory cytokine genes TNF and IL6, and downregulates the apoptotic-related genes BAX, BCL2 and RELA in human Caco-2 cells.

Colorectal carcinoma is one of the most common cancers in adults. As chemotherapy, the first-choice treatment for colorectal carcinoma, is often infeasible due to acquired tumor resistance and several adverse effects, it is important to discover and explore new molecules with better therapeutic action. Snake venom toxins have shown promising results with high cytotoxicity against tumor cells, but their mechanisms of action remain unclear. Here we examined how BjussuLAAO-II, an L-amino acid oxidase isolated from Bothrops jararacussu snake venom, exerts cytotoxicity towards colorectal adenocarcinoma human cells (Caco-2) and human umbilical vein endothelial cell line (HUVEC). A 24-h treatment with BjussuLAAO-II at 0.25 - 5.00 µg/mL diminished cell viability by decreasing (i) mitochondrial activity, assessed by reduction of 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide and resazurin; (ii) the activity of acid phosphatases; and (iii) lysosomal function, assessed by neutral red uptake. BjussuLAAO-II also increased intracellular levels of reactive oxygen species and DNA damage, as assessed by fluorescence and the comet assay, respectively. BjussuLAAO-II altered the expression of cell proliferation-related genes, as determined by RT-qPCR: it elevated the expression of the inflammatory cytokine genes TNF and IL6, and lowered the expression of the apoptotic-related genes BAX, BCL2, and RELA. Therefore, BjussuLAAO-II induces Caco-2 cells death by acting on multiple intracellular targets, providing important data for further studies to assess whether these effects are seen in both tumor and normal cells, with the aim of selecting this drug for possible therapeutic purposes in the future.

Protective effects of the exopolysaccharide Lasiodiplodan against DNA damage and inflammation induced by doxorubicin in rats: Cytogenetic and gene expression assays.

The lasiodiplodan (LS) is a ß-(1→6)-d-glucan produced by the fungus Lasiodiplodia theobromae and some of the biological activities of LS were reported as hypoglycemic, anticoagulant, anti-proliferative and anticancer action; however, its effects on DNA instability and modulation of gene expression are still unclear. Aims of study were investigate the genotoxic effects of lasiodiplodan, and its protective activity against DNA damage induced by doxorubicin (DXR) and its impact on the expression of genes associated with DNA damage and inflammatory response pathways. Therefore, Wistar rats were treated (15 days) orally with LS (5.0; 10 and 20mg/kg bw) alone and in combination with DXR (15mg/kg bw; administrated intraperitoneally on 14th day) as well as their respective controls: distilled water and DXR. Monitoring of DNA damage was assessed by comet and micronucleus (MN) assays and gene expression was evaluated by PCR-Arrays. Treatments with LS alone did not induce disturbances on DNA; when LS was given in combination with DXR, comet and MN formations were reduced to those found in the respective controls. Moreover, LS was able to reduce the disturbances on gene expressions induced by DXR treatment, since the animals that receive LS associated with DXR showed no alteration in the expression of genes related to DNA damage response. Also, DXR induced several up- and down-regulation of several genes associated to inflammatory process, while the animals that received LS+DXR had their gene expression patterns similar to those found in the control group. In conclusion, our results showed that LS did not induce disturbances on DNA stability and significantly reduce the DNA damage and inflammation caused by DXR exposure. In addition, we give further information concerning the molecular mechanisms associated to LS protective effects which seems to be a promising nutraceutical with chemopreventive potential.

Força muscular e mortalidade na lista de espera de transplante de fígado / Muscle strength and mortality while on a liver transplant waiting list

OBJETIVO: Avaliar a força de músculos respiratórios e de mão em pacientes na lista de espera para o transplante de fígado e associá-los a mortalidade. MATERIAIS E MÉTODOS: Foram estudados retrospectivamente 132 pacientes submetidos à avaliação fisioterapêutica de rotina e que esperavam o transplante de fígado. A força dos músculos ventilatórios foi avaliada por meio das pressões inspiratória e expiratória máximas e a força do membro superior por meio de dinamometria. Os pacientes foram divididos em dois grupos: grupo A, com 51 pacientes (14 mulheres, 50,1±12,3 anos) que morreram enquanto estavam na lista de espera e grupo B, com 81 pacientes (31 mulheres, 45,0±3,8 anos) que sobreviveram até o transplante de fígado. Foi utilizado o teste de t de Student com nível de significância de 5 por cento. RESULTADOS: Os valores médios da pressão inspiratória máxima (PImax) dos grupos A e B foram 65,7±28,0 e 77,5±33,8mmHg (p=0,04), respectivamente, e as pressões expiratórias máximas foram 72,9±32,9 e 84,4±33,1mmHg (p=0,07), respectivamente. Os valores médios da força da mão esquerda dos grupos A e B foram 18,5±8,1 e 21,5±10,5kgf (p=0,08), respectivamente, e da força da mão direita foram 20,2±9,7 e 23,5±12,5kgf (p=0,10), respectivamente. CONCLUSÕES: A PImax é menor nos pacientes que morreram enquanto aguardavam o transplante. No mesmo grupo, foi observado que a pressão expiratória máxima e a força da mão direita e esquerda foram menores, apesar de não apresentarem diferenças estatisticamente significante.

OBJECTIVE: To evaluate respiratory muscle strength and hand strength in patients on a liver transplant waiting list and to associate these with mortality. METHODS: one hundred and thirty-two patients who underwent routine physical therapy evaluation while waiting for liver transplantation were studied retrospectively. Respiratory muscle strength was assessed by measuring the maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP), and upper-limb strength was evaluated by dynamometry. The patients were divided into two groups: group A, consisting of 51 patients (14 females, 50.1±12.3 years) who died while on the waiting list; and group B, consisting of 81 patients (31 females, 45.0±3.8 years) who survived until the time of liver transplant. Student's t test was used with a 5 percent significance level. RESULTS: The mean MIP values for groups A and B were 65.7±28.0 and 77.5±33.8mmHg (p=0.04), respectively, and the mean MEP values were 72.9±32.9 and 84.4±33.1mmHg (p=0.07), respectively. The mean values for left-hand strength in groups A and B were 18.5±8.1 and 21.5±10.5kgf (p=0.08), and the mean values for right-hand strength were 20.2±9.7 and 23.5±12.5kgf (p=0.10), respectively. CONCLUSIONS: MIP was lower in the patients who died while waiting for liver transplantation. In the same group, it was observed that the MEP values and right and left-hand strength were numerically lower, although they did not reach statistically significant differences.

The Brazilian version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report the cross-cultural adaptation and validation into Brazilian-Portuguese of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children regardless the underlying disease. The Brazilian CHAQ was revalidated, while the CHQ has been derived from the Portuguese version. A total of 471 subjects were enrolled: 157 patients with JIA (27% systemic onset, 38% polyarticular onset, 9% extended oligoarticular subtype, and 26% persistent oligoarticular subtype) and 314 healthy children. The CHAQ discriminated clinically healthy subjects from JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and lower overall well-being scores when compared to their healthy peers. Also the CHQ discriminated clinically healthy subjects from JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being score when compared to their healthy peers. In conclusion the Brazilian versions of the CHAQ-CHQ are reliable and valid tools for the combined physical and psychosocial assessment of children with JIA.

[Antistreptolysin O titer profile in acute rheumatic fever diagnosis] / O perfil da antiestreptolisina O no diagnóstico da febre reumática aguda.

OBJECTIVE: To determine ASO titer profile by establishing ARF differential diagnoses of other diseases with high levels of ASO antibodies. METHODS: We investigated 78 patients with ARF at onset and follow-up, 22 with isolated chorea at onset, 45 with recurrent oropharyngeal tonsillitis, and 23 with recent flare of juvenile idiopathic arthritis. We tested ASO with automated particle-enhanced immunonephelometric assay (Behring(R)-Germany). The ASO (IU/ml) titers were assessed at the following time intervals: 0-7 days, 1-2 weeks, 2-4 weeks, 1-2 months, 2-4 months, 4-6 months, 6-12 months, 1-2 years, 2-3 years, 3-4 years, and 4-5 years after onset of ARF. RESULTS: ASO titers in patients diagnosed with ARF had a significant increase up to the 2-4-month time interval (P<0.0001). Baseline levels were observed afterwards in patients under regular penicillin prophylaxis. The levels of ASO in ARF were also significantly higher than in patients with isolated chorea, recurrent oropharyngeal infections or juvenile idiopathic arthritis (P=0.0025), when age-matched samples of these groups were compared. The testacute;s sensitivity was 73.3% and the specificity was 57.6%, and it was calculated taking into account the upper limit of normality at 320 IU/ml, as well as the established diagnosis of ARF. The testacute;s specificity and positive predictive value increased with rising or higher titers, being higher with titers above 960 UI/ml. CONCLUSION: This reappraisal of ASO profile in ARF patients indicates a remarkable response during the acute phase, and that points to the extent to which ASO levels may differentiate ARF from other diseases with high levels of ASO antibodies, as coincidental but unrelated streptococcal infection or chronic arthritis flareup.

[Mucosal immune response development: breastfeeding and environmental influence]. / Desenvolvimento da resposta imune de mucosas: influências do aleitamento materno e ambientais.

A review of the current knowledge of mucosal immune response development indicates that migration of immunocytes to mucosal surfaces is an early event during fetal life. The morphologic development of gut-associated lymphoid tissues (lymphoid follicles, Peyer's patches and tonsils) occurs from 11-20 weeks' gestation upwards. But they are active only after birth, when usually antigenic challenge takes place. The complete development of secretory immunity is a postnatal achievement. In infancy, some environmental factors such as feeding and oral antigenic challenge seems to modulate immune response development. Breastfeeding, by means of antiinfectious, antiinflammatory and immunomodulating properties, besides completing infant secretory immunity, also stimulates immunological maturation on mucosal surfaces.

The treatment of allergic rhinitis improves the recovery from asthma and upper respiratory infections.

Forty-six asthmatic children with repeated respiratory infections presented symptoms of allergic rhinitis. All patients were treated locally for allergic rhinitis either with disodium cromoglycate or beclomethasone dipropionate. After six months of treatment, 95% of the children showed improvement of allergic rhinitis and 84% improvement of bronchial asthma, as well as fewer infections. We concluded that allergic rhinitis plays an important role in facilitating infections of the upper respiratory tract, and a possible association of rhinitis, viral infections and bronchial asthma is discussed.

Gut intraepithelial lymphocyte counts in neonates, infants and children.

Intraepithelial lymphocyte (IEL) counts were histologically assessed in the jejunum, ileum and appendix of 39 neonates (0-28 days), 32 infants (1-9 months) and 13 children (1-9 years). Small intestinal mucosa samples were obtained from 73 autopsies, and from 8 surgical and 3 aspirative biopsies. IEL counts of specimens from the jejunum, ileum and appendix gave similar results in the same patient. The number of IEL counts was significantly lower in neonates for all three segments. The difference between infants and children was more marked in the jejunum than in the ileum, although this was not significant. In the appendix, there was no difference between the different age groups. Our results indicate that postnatal expansion of IEL occurs homogeneously along the gut after the neonatal period.

Assessment of gut intraepithelial lymphocytes during late gestation and the neonatal period.

Intraepithelial lymphocyte counts (IEL % enterocytes) were carried out in histological samples of jejunal, ileal and appendiceal mucosa of 39 neonates, aged from birth to 28 days. Correlations between IEL counts and developmental factors, namely gestational age, birth weight and intrauterine growth, as well as neonatal infections or feeding state were performed. No significant differences were observed among neonates grouped according to birth weight, intrauterine growth or neonatal infections. The pattern of feeding, however was associated with significantly higher IEL counts (p < 0.02) in the ileum in oral/enterally fed neonates than in the unfed or parenterally fed. Full-term neonates also had higher counts in the ileum (p < 0.02). In this group, oral/enterally fed neonates had the higher values. Thus, besides in utero development, the pattern of feeding might be considered as an important modulating factor on IEL postnatal expansion.

Surto de metemoglobinemia na enfermaria de pediatria do HCRP. Relato de 26 casos. / An outbreak of methemoglobinemia in the pediatric unit of the \"Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto\". Report of 26 cases

Os autores relatam um surto de metemoglobinemia na Enfermaria de Pediatria e Bercario Externo do HCRP, causado por tinta de marcar fraldas contendo nitrobenzol (anilina). Foram acometidas 26 criancas, sendo mais afetadas as que pesavam menos de 6 kg. Apos remocao das fraldas, retirada das criancas das incubadoras, administracao de acido ascorbico e azul de metileno, houve boa evolucao clinica com recuperacao de todos os casos. Ressaltam os autores a importancia da profilaxia evitando-se o uso de tintas com anilina ou, entao, a fervura ou autoclavagem das roupas marcadas com tais tintas devendo ser entregues ao uso somente 12 horas apos aquele procedimento