Hydroalcoholic Leaf Extract of Punica granatum, alone and in Combination with Calcium Hydroxide, Is Effective against Mono- and Polymicrobial Biofilms of Enterococcus faecalis and Candida albicans.

Failures in endodontic treatments are mostly associated with the difficulty in eradicating microbes of the root canal system, highlighting the need to develop novel effective antimicrobials. Punica granatum (pomegranate) leaf hydroalcoholic extract may be a potential alternative in canal dressing, owing to its antimicrobial properties. The objective of this study was to evaluate the antimicrobial activity of hydroalcoholic leaf extract of Punica granatum (HEPg) alone or in combination with calcium hydroxide (Ca(OH)2) against Enterococcus faecalis and Candida albicans in isolation and in mono- and polymicrobial biofilms. Microdilution tests in broth and assays for inhibition of biofilm formation were carried out to evaluate the antimicrobial properties of HEPg and HEPg + Ca(OH)2 against Enterococcus faecalis and Candida albicans. The cytotoxicity of HEPg in HaCaT cells was evaluated by MTT assay. HEPg and HEPg + Ca(OH)2 exerted significant antimicrobial activity against planktonic cells and mono- and polymicrobial biofilms. The combination of Punica granatum extract with Ca(OH)2 appears to be a promising alternative in endodontic treatments, which could be tested in vivo to confirm the efficacy of this mixture in disinfecting root canal systems.

Tuberculose intratorácica na forma pseudotumoral e óssea como manifestação de doença granulomatosa crônica / Intrathoracic tuberculosis in the pseudotumoral and bone form as a manifestation of chronic granulomatous disease

A doença granulomatosa crônica (DGC) é um erro inato da imunidade de fagócitos, e ocorre em decorrência de mutações que afetam componentes da enzima NADPH oxidase. Os pacientes são suceptíveis a infecções graves e letais por fungos e bactérias. O objetivo deste trabalho é relatar o caso de um lactente com DGC que apresentou manifestação clínica de tuberculose (TB) intratorácica na forma pseudotumoral e óssea iniciada no período neonatal. O diagnóstico de DGC foi realizado através do teste de DHR e, após o início da profilaxia com sulfametoxazoltrimetroprima e itraconazol, o paciente manteve-se estável clinicamente. A mãe e a irmã também apresentaram DHR alterados, a análise genética revelou uma mutação ligada ao X no exon 2 do gene CYBB c.58G>A, levando uma alteração em G20R. É fundamental que o diagnóstico seja realizado o mais precocemente possível, a fim de instituir as orientações aos familiares e tratamento adequado, reduzindo assim complicações infecciosas e melhorando prognóstico.

Chronic granulomatous disease (CGD) is an inborn error of phagocyte immunity and occurs as a resulto f mutations that affect components of the NADPH oxidase enzyme. Patients are susceptible to serious and lethal fungal and bacterial infections. The aim of this paper is to report a case an infant with CGD who presented clinical manifestations of intrathoracic tuberculosis (TB) in the pseudotumoral and bone form, which started in the neonatal period. The diagnosis of CGD was performed using the DHR test and, after starting prophylaxis with sulfamethoxazole-trimethoprim and itraconazole, the patient remained clinically stable. The mother and sister also had altered DHR, genetic analysis revealed an X-linked mutation in exon 2 of the CYBB gene c.58G>A, leading to an alteration in G20R. It is essential that the diagnosis is made as early as possible, in order to establish guidelines for Family members and adequate treatment, thus reducing infectious complications and improving prognosis.

CD40 Ligand Deficiency in Latin America: Clinical, Immunological, and Genetic Characteristics.

CD40 ligand (CD40L) deficiency is a rare inborn error of immunity presenting with heterogeneous clinical manifestations. While a detailed characterization of patients affected by CD40L deficiency is essential to an accurate diagnosis and management, information about this disorder in Latin American patients is limited. We retrospectively analyzed data from 50 patients collected by the Latin American Society for Immunodeficiencies registry or provided by affiliated physicians to characterize the clinical, laboratory, and molecular features of Latin American patients with CD40L deficiency. The median age at disease onset and diagnosis was 7 months and 17 months, respectively, with a median diagnosis delay of 1 year. Forty-seven patients were genetically characterized revealing 6 novel mutations in the CD40LG gene. Pneumonia was the most common first symptom reported (66%). Initial immunoglobulin levels were variable among patients. Pneumonia (86%), upper respiratory tract infections (70%), neutropenia (70%), and gastrointestinal manifestations (60%) were the most prevalent clinical symptoms throughout life. Thirty-five infectious agents were reported, five of which were not previously described in CD40L deficient patients, representing the largest number of pathogens reported to date in a cohort of CD40L deficient patients. The characterization of the largest cohort of Latin American patients with CD40L deficiency adds novel insights to the recognition of this disorder, helping to fulfill unmet needs and gaps in the diagnosis and management of patients with CD40L deficiency.

Gross Motor Function in Children with Congenital Zika Syndrome.

BACKGROUND: Little information on gross motor function of congenital Zika syndrome (CZS) children is available. OBJECTIVES: To evaluate gross motor function in CZS children aged up to 3 years, and its associated factors and changes in a minimum interval of 6 months. METHODS: One hundred children with CZS and cerebral palsy (36 with confirmed and 64 with presumed CZS) were evaluated with the Gross Motor Function Classification System (GMFCS) and Gross Motor Function Measure (GMFM-88/GMFM-66). Forty-six were reevaluated. Wilcoxon tests, Wilcoxon tests for paired samples, percentile scores, and score changes were performed. RESULTS: Clinical and socioeconomic characteristics (except maternal age), GMFM scores and GMFCS classification of confirmed and probable cases, which were analyzed together, were similar. The mean age was 25.6 months (±5.5); the median GMFM-88 score was 8.0 (5.4-10.8); and the median GMFM-66 score was 20.5 (14.8-23.1); 89% were classified as GMFCS level V. Low economic class, microcephaly at birth, epilepsy, and brain parenchymal volume loss were associated with low GMFM-66 scores. The median GMFM-66 percentile score was 40 (20-55). On the second assessment, the GMFM-66 scores in two GMFCS level I children and one GMFCS level IV child improved significantly. In one GMFCS level III child, one GMFCS level IV child, and the group of GMFCS level V children, no significant changes were observed. CONCLUSIONS: Almost all CZS children had severe cerebral palsy; in the third year of life, most presented no improvement in gross motor function and were likely approaching their maximal gross motor function potential.

Maternal and congenital infections arising from Zika, dengue and Chikungunya arboviruses in Salvador, Brazil.

BACKGROUND: Salvador was one of the Brazilian cities most affected during the 2015 Zika virus (ZIKV) outbreak. METHODS: A cross-sectional study was performed with enrolment of parturients and their newborns. RESULTS: Positive IgM antibodies for ZIKV, dengue (DENV) and Chikungunya (CHIKV) were present in 6.9, 11.9 and 22.8% of the parturients, and IgG antibodies were detected in 72.3, 92.3 and 38.6%, respectively. No cases of DENV congenital infection were identified. ZIKV and CHIKV congenital infections were observed in 16.5 and 13% of newborns, respectively. CONCLUSIONS: High exposure rates to the three arboviruses and the identification of newborns with ZIKV and CHIKV congenital infections reinforces the necessity of ZIKV and CHIKV prenatal and neonatal screening in endemic regions.

The extended understanding of chronic granulomatous disease.

PURPOSE OF REVIEW: We briefly address the advances in genetics, pathophysiology, and phenotypes of chronic granulomatous disease (CGD). This is one of the most studied primary immunodeficiencies, which comprise mutations in genes encoding the different subunits of the NADPH oxidase system. Those mutations lead to defective reactive oxygen species production, and consequently a failure to eliminate pathogens. RECENT FINDINGS: Patients with CGD are susceptible to fungal, bacterial, and parasitic infections. Other symptoms, as systemic adverse effects to BCG vaccine and hyperinflammation, are also important clinical conditions in this disease. This wide-ranging clinical spectrum of CGD comes from heterogeneity of mutations, X-linked-CGD or autosomal recessive inheritance, and diverse environmental pressure factors. Early accurate diagnosis and prompt treatment are necessary to diminish the consequences of the disease. The most used diagnostic tests are dihydrorhodamine, cytochrome c reduction, and luminol-enhanced chemiluminescence assay. SUMMARY: The determination of mutations is essential for diagnosis confirmation and genetic counseling. CGD treatment usually includes prophylactic antibiotics and antifungals. Prophylactic recombinant human interferon-γ, immunosuppressors or immune modulators may be, respectively, indicated for preventing infections or inflammatory manifestations. Hematopoietic stem cell transplantation and gene therapy are currently the available options for curative treatment of CGD.