Host defense peptide IDR-1002 associated with ciprofloxacin as a new antimicrobial and immunomodulatory strategy for dental pulp revascularization therapy.

Regenerative therapies such as dental pulpal revascularization appear as an option for traumatized immature permanent teeth. However, the triple antibiotic paste - TAP (metronidazole, minocycline, and ciprofloxacin), used for these therapies, can generate cytotoxicity and dentin discoloration. In contrast, host defense peptides (HDPs) are promising antimicrobial and immunomodulatory biomolecules for dentistry. This study aimed to evaluate in vitro the antimicrobial activity (against Staphylococcus aureus and Enterococcus faecalis) and the immunomodulatory potential (by the evaluation of IL-1α, IL-6, IL-12, IL-10, TNF-α and NO, in RAW 264.7 macrophages and IL-6, TGF-ß and NO, in L929 fibroblast) of synthetic peptides (DJK-6, IDR-1018, and IDR-1002), compared to TAP in an in vitro infection model containing heat-killed antigens from E. faecalis and S. aureus. Furthermore, the synergistic potential of ciprofloxacin and IDR-1002 was evaluated by checkerboard. Ciprofloxacin was the best antimicrobial of TAP, besides acting in synergism with IDR-1002. TAP was pro-inflammatory (p < 0.05), while the association of ciprofloxacin and IDR-1002 presented an anti-inflammatory profile mainly in the presence of both heat-killed antigens (p < 0.05). Based on these results, ciprofloxacin associated with IDR-1002 may demonstrate an efficient antimicrobial and immunomodulatory action in this in vitro model. Further in vivo studies may determine the real potential of this combination.

Zinc treatment ameliorates diarrhea and intestinal inflammation in undernourished rats.

BACKGROUND: WHO guidelines recommend zinc supplementation as a key adjunct therapy for childhood diarrhea in developing countries, however zinc's anti-diarrheal effects remain only partially understood. Recently, it has been recognized that low-grade inflammation may influence stunting. In this study, we examined whether oral zinc supplementation could improve weight, intestinal inflammation, and diarrhea in undernourished weanling rats. METHODS: Rats were undernourished using a northeastern Brazil regional diet (RBD) for two weeks, followed by oral gavage with a saturated lactose solution (30 g/kg) in the last 7 days to induce osmotic diarrhea. Animals were checked for diarrhea daily after lactose intake. Blood was drawn in order to measure serum zinc levels by atomic absorption spectroscopy. Rats were euthanized to harvest jejunal tissue for histology and cytokine profiles by ELISA. In a subset of animals, spleen samples were harvested under aseptic conditions to quantify bacterial translocation. RESULTS: Oral zinc supplementation increased serum zinc levels following lactose-induced osmotic diarrhea. In undernourished rats, zinc improved weight gain following osmotic diarrhea and significantly reduced diarrheal scores by the third day of lactose intake (p < 0.05), with improved jejunum histology (p < 0.0001). Zinc supplementation diminished bacterial translocation only in lactose-challenged undernourished rats (p = 0.03) compared with the untreated challenged controls and reduced intestinal IL-1ß and TNF-α cytokines to control levels. CONCLUSION: Altogether our findings provide novel mechanisms of zinc action in the setting of diarrhea and undernutrition and support the use of zinc to prevent the vicious cycle of malnutrition and diarrhea.

Evaluation of mutagenic, teratogenic, and immunomodulatory effects of Annona nutans hydromethanolic fraction on pregnant mice.

Plants such as Annona nutans used in folk medicine have a large number of biologically active compounds with pharmacological and/or toxic potential. Moreover, pregnant women use these plants indiscriminately, mainly in the form of teas, without being aware of the harm that they could cause to the health of the embryo/fetus. Therefore, it is necessary to analyze the potential toxic effects of medicinal plants during gestation. The present study aimed to evaluate the effects of A. nutans hydromethanolic fraction leaves (ANHMF) on mutagenic and immunomodulatory activity, reproductive performance, and embryo-fetal development in pregnant female mice. The animals (N=50 female and 25 male) were divided into 5 groups: Control, Pre-treatment, Organogenesis, Gestational, and Pre+Gestational. The results indicate that ANHMF mainly contains flavonoid and other phenolic derivatives. It was found that it does not exhibit any mutagenic or immunomodulatory activity, and it does not cause embryo-fetal toxicity. Based on the protocols used in the present studies, our analyses confirm that it is safe to use ANHMF during pregnancy.

Dietary management of urea cycle disorders: European practice.

BACKGROUND: There is no published data comparing dietary management of urea cycle disorders (UCD) in different countries. METHODS: Cross-sectional data from 41 European Inherited Metabolic Disorder (IMD) centres (17 UK, 6 France, 5 Germany, 4 Belgium, 4 Portugal, 2 Netherlands, 1 Denmark, 1 Italy, 1 Sweden) was collected by questionnaire describing management of patients with UCD on prescribed protein restricted diets. RESULTS: Data for 464 patients: N-acetylglutamate synthase (NAGS) deficiency, n=10; carbamoyl phosphate synthetase (CPS1) deficiency, n=29; ornithine transcarbamoylase (OTC) deficiency, n=214; citrullinaemia, n=108; argininosuccinic aciduria (ASA), n=80; arginase deficiency, n=23 was reported. The majority of patients (70%; n=327) were aged 0-16y and 30% (n=137) >16y. Prescribed median protein intake/kg body weight decreased with age with little variation between disorders. The UK tended to give more total protein than other European countries particularly in infancy. Supplements of essential amino acids (EAA) were prescribed for 38% [n=174] of the patients overall, but were given more commonly in arginase deficiency (74%), CPS (48%) and citrullinaemia (46%). Patients in Germany (64%), Portugal (67%) and Sweden (100%) were the most frequent users of EAA. Only 18% [n=84] of patients were prescribed tube feeds, most commonly for CPS (41%); and 21% [n=97] were prescribed oral energy supplements. CONCLUSIONS: Dietary treatment for UCD varies significantly between different conditions, and between and within European IMD centres. Further studies examining the outcome of treatment compared with the type of dietary therapy and nutritional support received are required.

Huperzia quadrifariata and Huperzia reflexa alkaloids inhibit acetylcholinesterase activity in vivo in mice brain.

Huperzine A, a Lycopodium alkaloid produced by Chinese folk herb Huperzia serrata (Lycopodiaceae), has been shown to be a promising agent for the treatment of Alzheimer's disease due to its potent acetylcholinesterase (AChE) activity, as well its efficacy in the treatment of memory of aged patients. Thus, the effects of two Huperzia species of habitats in Brazil (H. quadrifariata and H. reflexa) with described in vitro AChE inhibition activities were studied and their effects on mice brain AChE inhibition were determined after a single intraperitoneal (i.p.) injection. The alkaloid extracts were administered to mice in various doses (10, 1 and 0.5mg/kg) and acetylcholinesterase activity was measured post mortem in two brain areas using the Ellman's colorimetric method. The AChE activity was found to be significantly reduced in both the cortex and hippocampus, although this activity was less potent than that of reference inhibitor huperzine A (0.5mg/kg). Thus, it appears that H. quadrifariata and H. reflexa alkaloid extracts, shown to inhibit acetylcholinesterase in vitro, also have very potent in vivo effects, suggesting that the Huperzia species may still constitute a promising source of compounds with pharmaceutical interest for Alzheimer's disease.

The Amazonian herbal Marapuama attenuates cognitive impairment and neuroglial degeneration in a mouse Alzheimer model.

UNLABELLED: Alzheimer's disease (AD) is expected to affect more than 22 million people worldwide by 2025, causing devastating suffering and enormous costs to families and society. AD is a multifactorial disease, with a complex pathological mosaic. In rodents, AD-like dementia can be induced by cerebral microinjection of Aß peptide, leading to amyloid deposits, amnesia and various features of neurodegeneration. Marapuama (Ptychopetalum olacoides) is regarded as a "brain tonic" in the Amazon region and shows a nootropic profile in rodents. AIM OF THE STUDY: Because a specific extract (POEE) of Marapuama was shown to possess promnesic and anti-amnesic properties, the aim of this study was to verify if POEE is also effective against Aß(1-42)-induced cognitive deficit in mice. Additionally, Aß deposits (Congo red), GFAP immunoreactivity (immunohistochemistry), and neurodegenerative changes in the hippocampal pyramidal layer (Nissl) were examined as measures of Aß(1-42)-induced neurodegeneration. MATERIALS AND METHODS: CF1 mice were subjected to the experimental Alzheimer model with the Aß(1-42) i.c.v. administration. The effects of POEE 800 mg/kg were evaluated over 14 consecutive days of treatment. RESULTS: The data show that 14 days of oral treatment with POEE (800 mg/kg) was effective in preventing Aß-induced cognitive impairment, without altering the levels of BDNF and with parallel reductions in Aß deposits and astrogliosis. CA1 hippocampus loss induced by Aß(1-42) was also diminished in POEE-treated mice. CONCLUSION: This study offers evidence of functional and neuroprotective effects of two weeks treatment with a Ptychopetalum olacoides extract against Aß peptide-induced neurotoxicity in mice. Given the multifactorial nature of neurodegeneration, the considerable potential for an AChE inhibitor displaying associated neuroprotective properties such as here reported warrants further clinic evaluation.

Dietary carotenoid-rich pequi oil reduces plasma lipid peroxidation and DNA damage in runners and evidence for an association with MnSOD genetic variant -Val9Ala.

Physical training induces beneficial adaptations; however, exhausting exercise increases reactive oxygen species generation, resulting in damage to DNA and tissues. Pequi (Caryocar brasiliense), a fruit of the Brazilian Cerrado, contains a carotenoid-rich oil. We investigated whether pequi oil had antioxidant effects in runners. Evaluations were made after outdoor races before and after ingestion of 400 mg pequi-oil capsules for 14 days. Blood samples were taken after races and submitted to comet and TBARS assays and biochemical analyses of creatine kinase (CK), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). To determine if the protective effects of pequi-oil were influenced by antioxidant enzyme genotypes, MnSOD (-Val9Ala), CAT (-21A/T) and GPX1 (Pro198Leu) gene polymorphisms were also investigated. Pequi oil was efficient in reducing tissue injuries evaluated for AST and ALT, particularly in women, and in reducing DNA damages in both sexes. Except for CK levels, the results were influenced by MnSOD genotypes; heterozygous excess was related to less DNA damage, tissue injury and lipid peroxidation, besides presenting a better response to pequi oil against exercise-induced damage.

Consumo de mistura mineral e desempenho de bezerros alimentados com sucedâneos do leite / Intake of mineral supplement and performance of calves fed milk replaces

Utilizaram-se 42 bezerros da raça Holandesa para avaliação do consumo de mistura mineral (MM), até os 60 dias. Os animais foram distribuídos em três grupos conforme o sucedâneo fornecido: grupo soro/leite + MM (SLMM); grupo soro + MM (SMM); e grupo soja/leite + MM (SOMM). Os animais receberam concentrado, feno, MM e água à vontade. A avaliação do ganho de peso foi feita semanalmente. A concentração de glicose plasmática foi medida aos 7, 14 e 21 dias de vida, antes do fornecimento da dieta, e às 3, 6 e 9 horas após a primeira refeição. Realizaram-se hemogramas semanais para avaliações clínicas. Aos 30 e aos 60 dias, colheram-se sangue e urina de cinco animais de cada grupo, os quais foram sacrificados para obtenção de fragmentos do fígado, para análises de minerais. Os animais do grupo SMM apresentaram menores consumos de concentrado e matéria seca total (MST) entre a sexta e oitava semanas (P<0,05), com consumo de concentrado de 674,72; 1.080,02 e 1.223,65g/a/d e consumo de MST de 699,33; 1.134,31 e 1.287,84g/a/d, para os animais dos grupos SMM, SLMM e SOMM, respectivamente. No consumo de feno, houve interação grupos versus semanas (P<0,05). O ganho de peso foi maior nos animais do grupo SOMM, 2,18kg/a/d que nos do grupo SMM, 1,13kg/a/d (P<0,05). O consumo médio da MM no primeiro mês foi de 9,00g/a/d e da quinta a oitava semanas foi 4,62g/a/d. A concentração de glicose plasmática foi diferente entre as idades e os tempos (P<0,05).

Forty-two Holstein calves were used to evaluate the mineral supplement (MS) intake up to 60-day-old. The calves were divided into three groups, according to the milk replacer: whey/milk + MS (WMMS); whey + MS (WMS) and soy/milk + MS (SMMS). Commercial calf starter, hay, MS and water were offered "ad libitum", and the intake was measured daily. Body weight was monitored once a week and blood glucose levels were quantified on 14, 21 and 28-day-old and also before the supply of the diets, 3, 6 and 9 hours after feeding. Blood samples were collected weekly for blood count. On 30 and 60-day-old, five calves of each group had blood and urine samples collected for serum copper determination. After then, the animals were slaughtered and liver fragments were analyzed for minerals contents. It was found that between the sixth and eighth weeks, the calves from WMS group decreased the intake (P<0.05) of starter 674.72g/day and total dry matter (TDM) 699.33 when compared to the calves from WMMS and SMMS groups, which consumed an average of 1,080.02 and 1,223.65g/day of concentrate and 1,134.31 and 1,287.84g/day of TDM respectively. Animals from SMMS group presented higher weight gain (2.18kg/week) than MMS ones (1.13kg/week; P<0.05). The intake mean of MM in the first month was 9.00g/a/d and after the first month was 4.62g/a/d. Blood glucose levels were different among ages and times after feeding (P<0.05).

[Sesame seed (Sesamum indicum, L.). II. Use of sesame flour in protein mixtures]. / Estudo da semente de gergelim (Sesamum indicum, L.) II. Emprego da farinha de gergelim em misturas proteicas.

The results obtained in the first part of this study demonstrated that the sesame flour protein is of reasonable quality and can be utilized, although it has a low lysine content and is rich in sulfur amino acids. Based on the initial data, the sesame flour was supplemented with other meals: "carioca" beans, pigeon pea, and soybean. Nine diets were prepared and the best combination was that of 50% sesame flour protein and 50% pigeon pea, the PER of which was 2.28. Breads were made with these systems, as follows: 100% sesame flour, 100% wheat flour, 50% sesame flour + 50% wheat flour; 30% sesame flour + 70% wheat flour; 30% sesame flour + 30% soybean flour + 40% wheat flour. These were evaluated through sensory analysis by a grading system. Good acceptance was obtained with the bread prepared with 30% sesame flour + 70% wheat flour. Its external and internal appearance, as well as its organoleptic characteristics were close to the bread, with 100% wheat flour. Sesame flour at the 50% proportion gave a bread of medium quality. The protein mixtures of sesame flour and soybean flour were well accepted. Some of the panel members reported that it had a taste somewhat like integral bread.