Propolis in Oral Healthcare: Antibacterial Activity of a Composite Resin Enriched With Brazilian Red Propolis.

The aim of this study was to obtain a Brazilian red propolis (BRP) enriched composite resin and to perform the characterization of its antibacterial activity, mechanical, and physical-chemical properties. Brazilian red propolis ethyl acetate extract (EABRP) was characterized by LC-ESI-Orbitrap-FTMS, UPLC-DAD, antibacterial activity, total flavonoids content, and radical scavenging capacity. BRP was incorporated to a commercial composite resin (RC) to obtain BRP enriched composite at 0.1, 0.15 and 0.25% (RP10, RP15 and RP25, respectively). The antibacterial activity RPs was evaluated against Streptococcus mutans by contact direct test and expressed by antibacterial ratio. The RPs were characterized as its cytotoxicity against 3T3 fibroblasts, flexural strength (FS), Knoop microhardness (KHN), post-cure depth (CD), degree of conversion (DC%), water sorption (Wsp), water solubility (Wsl), average roughness (Ra), and thermal analysis. Were identified 50 chemical compounds from BRP extract by LC-ESI-Orbitrap-FTMS. EABRP was bacteriostatic and bactericide at 125 and 500 µg/ml, respectively. The RP25 exhibited antibacterial ratio of 90.76% after 1 h of direct contact with S. mutans (p < 0.0001) while RC no showed significative antibacterial activity (p = 0.1865), both compared with cell control group. RPs and RC no showed cytotoxicity. RPs exhibited CD from 2.74 to 4.48 mm, DC% from 80.70 to 83.96%, Wsp from 17.15 to 21.67 µg/mm3, Wsl from 3.66 to 4.20 µg/mm3, Ra from 14.48 to 20.76 nm. RPs showed thermal resistance between 448-455°C. The results support that propolis can be used on development of modified composite resins that show antibacterial activity and that have compatible mechanical and physical-chemical properties to the indicate for composite resins.

Epidemiological, temporal and spatial dynamics of leprosy in a municipality in northeastern Brazil (2008-2017): an ecological study.

INTRODUCTION: Leprosy is a chronic infectious disease caused by Mycobacterium leprae.This study aimed to analyze the epidemiological, temporal, and spatial dynamics ofleprosy in a municipality in northeastern Brazil. METHODS: This is an ecological study on new leprosy cases in the population of Arapiraca (Alagoas, Northeast Region, Brazil), from 2008 to 2017. Data extracted from a national database were analyzed forepidemiological indicators, factors associated with physical disabilities, and spatialanalysis in the neighborhoods of Arapiraca. RESULTS: A total of 292 new cases of leprosy were recorded, particularly occurring among the following groups: women, the age group of 46-59 years, brown-skinned individuals, people with less than eight years of schooling, and urban residents; the new cases were also predominantly the tuberculoid form and were of the paucibacillary classification of the disease. Almost 1/3 of the people had some degree of physical disability, which was mainly associated with the group 60 years of age and older, black ethnicity, and the multibacillary clinical form of leprosy. The joinpoint regression showed a stationary temporal behavior of indicators. There was a heterogeneous spatial distribution with active transmission areas, especially in the neighborhoods Primavera, Baixão, Ouro Preto, and downtown. CONCLUSIONS: The epidemiological indicators revealed complexity in the process of leprosy development. These spatial and temporal studies are relevant to help in the planning, monitoring, and guidance of interventions in the municipality. The spatial analysis showed heterogeneous distribution in the analyzed neighborhoods.

Restoration of Cyclo-Gly-Pro-induced salivary hyposecretion and submandibular composition by naloxone in mice.

Cyclo-Gly-Pro (CGP) attenuates nociception, however its effects on salivary glands remain unclear. In this study, we investigated the acute effects of CGP on salivary flow and composition, and on the submandibular gland composition, compared with morphine. Besides, we characterized the effects of naloxone (a non-selective opioid receptor antagonist) on CGP- and morphine-induced salivary and glandular alterations in mice. After that, in silico analyses were performed to predict the interaction between CGP and opioid receptors. Morphine and CGP significantly reduced salivary flow and total protein concentration of saliva and naloxone restored them to the physiological levels. Morphine and CGP also reduced several infrared vibrational modes (Amide I, 1687-1594cm-1; Amide II, 1594-1494cm-1; CH2/CH3, 1488-1433cm-1; C = O, 1432-1365cm-1; PO2 asymmetric, 1290-1185cm-1; PO2 symmetric, 1135-999cm-1) and naloxone reverted these alterations. The in silico docking analysis demonstrated the interaction of polar contacts between the CGP and opioid receptor Cys219 residue. Altogether, we showed that salivary hypofunction and glandular changes elicited by CGP may occur through opioid receptor suggesting that the blockage of opioid receptors in superior cervical and submandibular ganglions may be a possible strategy to restore salivary secretion while maintaining antinociceptive action due its effects on the central nervous system.

Epidemiological, temporal and spatial dynamics of leprosy in a municipality in northeastern Brazil (2008-2017): an ecological study

Abstract INTRODUCTION: Leprosy is a chronic infectious disease caused by Mycobacterium leprae.This study aimed to analyze the epidemiological, temporal, and spatial dynamics ofleprosy in a municipality in northeastern Brazil. METHODS: This is an ecological study on new leprosy cases in the population of Arapiraca (Alagoas, Northeast Region, Brazil), from 2008 to 2017. Data extracted from a national database were analyzed forepidemiological indicators, factors associated with physical disabilities, and spatialanalysis in the neighborhoods of Arapiraca. RESULTS: A total of 292 new cases of leprosy were recorded, particularly occurring among the following groups: women, the age group of 46-59 years, brown-skinned individuals, people with less than eight years of schooling, and urban residents; the new cases were also predominantly the tuberculoid form and were of the paucibacillary classification of the disease. Almost 1/3 of the people had some degree of physical disability, which was mainly associated with the group 60 years of age and older, black ethnicity, and the multibacillary clinical form of leprosy. The joinpoint regression showed a stationary temporal behavior of indicators. There was a heterogeneous spatial distribution with active transmission areas, especially in the neighborhoods Primavera, Baixão, Ouro Preto, and downtown. CONCLUSIONS: The epidemiological indicators revealed complexity in the process of leprosy development. These spatial and temporal studies are relevant to help in the planning, monitoring, and guidance of interventions in the municipality. The spatial analysis showed heterogeneous distribution in the analyzed neighborhoods.

Polyphenol profile by UHPLC-MS/MS, anti-glycation, antioxidant and cytotoxic activities of several samples of propolis from the northeastern semi-arid region of Brazil.

CONTEXT: Propolis has promising biological activities. Propolis samples from the Northeast of Bahia, Brazil - sample A from Ribeira do Pombal and B, from Tucano - were investigated, with new information regarding their biological activities. OBJECTIVE: This paper describes the chemical profile, antioxidant, anti-glycation and cytotoxic activities of these propolis samples. MATERIAL AND METHODS: Ethanol extracts of these propolis samples (EEP) and their fractions were analyzed to determine total phenolic content (TPC); antioxidant capacity through DPPH•, FRAP and lipid peroxidation; anti-glycation activity, by an in vitro glucose (10 mg/mL) bovine serum albumine (1 mg/mL) assay, during 7 d; cytotoxic activity on cancer (SF295, HCT-116, OVCAR-8, MDA-MB435, MX-1, MCF7, HL60, JURKAT, MOLT-4, K562, PC3, DU145) and normal cell lines (V79) at 0.04-25 µg/mL concentrations, for 72 h. The determination of primary phenols by ultra high-pressure liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS) and volatile organic compounds content by gas chromatography-mass spectrometry (GC-MS) were also performed. RESULTS: The EEP polar fractions exhibited up to 90% protection against lipid peroxidation. The IC50 value for anti-glycation activity of EEP was between 16.5 and 19.2 µg/mL, close to aminoguanidine (IC50 = 7.7 µg/mL). The use of UHPLC-MS/MS and GC-MS allowed the identification of 12 bioactive phenols in the EEP and 24 volatile compounds, all already reported. CONCLUSIONS: The samples present good antioxidant/anti-glycation/cytotoxic activities and a plethora of biologically active compounds. These results suggest a potential role of propolis in targeting ageing and diseases associated with oxidative and carbonylic stress, aggregating value to them.

The anti-hyperalgesic and anti-inflammatory profiles of p-cymene: Evidence for the involvement of opioid system and cytokines.

CONTEXT: Pain corresponds to the most frequent reason for visits to physicians, and its control by conventional drugs is accompanied by several side effects, making treatment difficult. For this reason, new chemical entities derived from natural products still hold great promise for the future of drug discovery to pain treatment. OBJECTIVE: The objective of this study was to evaluate the antinociceptive and anti-inflammatory profiles of p-cymene (PC), a monocyclic monoterpene, and its possible mechanisms of action. MATERIALS AND METHODS: Mice treated acutely with PC (25, 50, or 100 mg/kg, i.p.) were screened for carrageenan-induced hyperalgesia and the inflammatory components of its cascade (30-180 min), carrageenan-induced pleurisy (4 h), and tail-flick test (1-8 h). Also, we observed the PC effect on the generation of nitric oxide by macrophages and the activation of neurons in the periaqueductal gray (PAG) by immunofluorescence. RESULTS: PC reduced (p < 0.001) the hyperalgesia induced by carrageenan, TNF-α, dopamine, and PGE2. PC decrease total leukocyte migration (100 mg/kg: p < 0.01), neutrophils (50 and 100 mg/kg: p < 0.05 and 0.001), and TNF-α (25, 50, and 100 mg/kg: p < 0.01, 0.05, and 0.001, respectively), besides reducing NO production (p < 0.05) in vitro. PC produced antinociceptive effect in tail-flick test (p < 0.05), which was antagonized by naloxone, naltrindole, nor-BNI, and CTOP, and increased (p < 0.001) the number of c-Fos-immunoreactive neurons in PAG. DISCUSSION AND CONCLUSION: These results provide information about the anti-hyperalgesic and anti-inflammatory properties of PC suggesting a possible involvement of the opioid system and modulating some pro-inflammatory cytokines.

Reduced expression of IL-3 mediates intestinal mast cell depletion in diabetic rats: role of insulin and glucocorticoid hormones.

Rats turned diabetic by alloxan treatment are refractory to systemic anaphylactic shock, in a direct association with reduced intestinal haemorrhage and tissue response to antigen challenge. As diabetic rats show reduction in mast cell numbers in different body compartments, this study was undertaken to investigate the influence of alloxan diabetes on mast cell population as well as the expression of the mast cell growth factor interleukin (IL)-3 in the small intestine of rats. We also analysed the putative involvement of endogenous insulin and glucocorticoid hormones in this phenomenon. There was a significant decrease in the number of mast cells present in the small intestine (ileum segment) of diabetic rats. Likewise, the immunohistochemical analysis revealed that IL-3 labelling was markedly attenuated in diabetic rats, as compared with normal animals, a phenomenon which paralleled with a decreased mRNA expression as attested by Reverse transcriptase-polymerase chain reaction technique. Treatment with insulin and with the steroid receptor antagonist RU 486 restored basal mast cell numbers, normal levels of IL-3 labelling and mRNA expression for IL-3 in the ileum of diabetic rats. In conclusion, our findings show that there is a causative relationship between down-regulation of mast cell numbers and the expression of IL-3 associated with diabetic state. In addition, as both parameters were suppressed by administration of insulin and RU 486, it indicates that an imbalance between the systemic levels of insulin and glucocorticoid hormones seems to be implicated in the reduction in intestinal mast cell population and refractoriness to antigen provocation in alloxan diabetes.

Estudo dos mecanismos determinantes da hiporreatividade de mastócitos na diabetes experimental induzida por aloxana em ratos / Study of the determinant mechanisms of the hyporeactivity of mast cells in experimental diabetes induced by aloxan in rats

Neste trabalho objetivamos determinar o(s) mecanismo(s) envolvido(s) na refratariedade mastocitária associada ao estado diabético induzido por aloxana em ratos. Inicialmente constatamos que mastócitos peritoneais isolados de animais diabéticos mostraram-se hiporreativos à estimulação antigênica, fenômeno este que se mostrou extensivo a outros sítios do organismo incluindo pele, traquéia e intestino. Através do processo de transferência adotiva de células da cavidade pleural, verificamos que a repopulação mastocitária foi capaz de restaurar a reatividade de ratos diabéticos à provocação antigênica. Vimos ainda, que mastócitos provenientes de ratos diabéticos sensibilizados quando transferidos para animais normais, induziram uma resposta inflamatória de menor intensidade, sugerindo haver uma falha na reatividade destas células. Isto foi confirmado in vitro, quando mastócitos isolados mostraram-se menos reativos a estímulos como antígeno, bradicinina e composto 48/80, secretando menor quantidade de histamina e PGD2 que mastócitos normais. Mais ainda, mastócitos diabéticos apresentaram níveis elevados de AMPc em nítida associação com aumento no conteúdo de actina polimerizada e na taxa de apoptose. O pré-tratamento de ratos diabéticos com RU 486 foi capaz de inibir a refratariedade de mastócitos diabéticos, indicando clara associação deste fenômeno à elevação nos níveis de hormônios esteróides verificados na condição diabética. De forma particular, não foram identificadas alterações nos mastócitos presentes no timo de ratos diabéticos à despeito do marcado processo de atrofia tímica e elevação na deposição de matriz extracelular. A ausência de alteração na população mastocitária tímica sugere que esta encontra-se sob regulação diferente daquela presente em outros sítios do organismo, fenômeno este que precisa ser melhor investigado.