A fermented milk drink with Umbu (Spondias tuberosa) pulp and whey is effective for weight gain and re-nutrition in malnourished: An in vivo study in mice and children.

Malnutrition is considered one of the major public health problems worldwide and negatively affects the growth, development and learning of schoolchildren. This study developed and evaluated a fermented milk drink with added Umbu (Spondias tuberosa) pulp in the weight gain and renutrition of mice submitted to malnutrition by calorie restriction, and in malnourished children. The supplementation with this fermented milk drink contributed to an increase of 7.2 % in body weight, and 64.3 % in albumin, and a reduction of 35 % in cholesterol in malnourished mice. In humans, a group of nine malnourished children consumed a daily 200 mL serving of the milk drink (for 60 days). For humans, the fermented milk drink allowed an increase of 16.5 % in body weight, and 20.9 % in body mass index in malnourished children. In conclusion, fermented milk drink has a positive effect on the re-nutrition of malnourished mice and helps to improve the nutritional status of malnourished children.

Fabrication of Functional bioMOF-100 Prototype as Drug Delivery System for Breast Cancer Therapy.

Breast cancer is the most frequent cause of cancer death in women, representing the fifth leading cause of cancer death overall. Therefore, the growing search for the development of new treatments for breast cancer has been developed lately as well as drug delivery systems such as biocompatible metal-organic Frameworks (bio-MOFs). These may be promising and attractive for drug incorporation and release. The present study aims to develop a drug carrier system RCA (bioMOF-100 submitted to the activation process) containing incorporated curcumin (CCM), whose material surface is coated with folic acid molecules (FA) to promote the targeting of drug carrier systems to the tumor region. They were synthesized and characterized using several characterization techniques. The materials were submitted to drug encapsulation tests, whose encapsulation efficiency was 32.80% for CCM@RCA-1D. Using the 1H nuclear magnetic resonance (NMR) spectroscopy technique, it was possible to verify the appearance of signals referring to folic acid, suggesting success in the functionalization of these matrices. In vitro tests such as cell viability and type of cell death were evaluated in both series of compounds (CCM@RCA-1D, CCM@RCA-1D/FA) in breast tumor lines. The results revealed low toxicity of the materials and cell death by late apoptosis. Thus, these results indicate that the matrices studied can be promising carriers in the treatment of breast cancer.

Liposomal paclitaxel induces apoptosis, cell death, inhibition of migration capacity and antitumoral activity in ovarian cancer.

The main goal of this study is to evaluate the efficacy of the paclitaxel (PTX) drug formulated with a liposomal nanosystem (L-PTX) in a peritoneal carcinomatosis derived from ovarian cancer. In vitro cell viability studies with the human ovarian cancer line A2780 showed a 50% decrease in the inhibitory concentration for L-PTX compared to free PTX. A2780 cells treated with the L-PTX formulation demonstrated a reduced capacity to form colonies in comparison to those treated with PTX. Cell death following L-PTX administration hinted at apoptosis, with most cells undergoing initial apoptosis. A2780 cells exhibited an inhibitory migration profile when analyzed by Wound Healing and real-time cell analysis (xCELLigence) methods after L-PTX administration. This inhibition was related to decreased expression of the zinc finger E-box-binding homeobox 1 (ZEB1) and transforming growth factor 2 (TGF-ß2) genes. In vivoL-PTX administration strongly inhibited tumor cell proliferation in ovarian peritoneal carcinomatosis derived from ovarian cancer, indicating higher antitumor activity than PTX. L-PTX formulation did not show toxicity in the mice model. This study demonstrated that liposomal paclitaxel formulations are less toxic to normal tissues than free paclitaxel and are more effective in inhibiting tumor cell proliferation/migration and inducing ZEB1/TGF-ß2 gene expression.

Combined paclitaxel-doxorubicin liposomal results in positive prognosis with infiltrating lymphocytes in lung metastasis.

Aim: To investigate the effect of liposomes containing the classical cytotoxic drugs paclitaxel and doxorubicin (Lipo-Pacli/Dox), against a metastatic breast cancer model. We also investigated if Lipo-Pacli/Dox was capable of reverting the tolerogenic environment of metastatic lesions. Materials & methods: Immunogenic cell death induction by the Pacli/Dox combination was assessed in vitro. Antitumor activity and in vivo safety of Lipo-Pacli/Dox were evaluated using a 4T1 breast cancer mouse model Results: Lipo-Pacli/Dox, with a size of 189 nm and zeta potential of -5.01 mV, promoted immune system activation and partially controlled the progression of pulmonary metastasis. Conclusion: Lipo-Pacli/Dox was useful to control both primary tumor and lung metastasis in breast cancer (4T1) mice model. Additionally, Lipo-Pacli/Dox acts as an immunological modulator for this metastatic breast cancer model.

Ruthenium(II)/Benzonitrile Complex Induces Cytotoxic Effect in Sarcoma-180 Cells by Caspase-Mediated and Tp53/p21-Mediated Apoptosis, with Moderate Brine Shrimp Toxicity.

Ruthenium(II)/benzonitrile complexes have demonstrated promising anticancer properties. Considering that there are no specific therapies for treating sarcoma, we decided to evaluate the cytotoxic, genotoxic, and lethal effects of cis-[RuCl(BzCN)(phen)(dppb)]PF6 (BzCN = benzonitrile; phen = 1,10-phenanthroline; dppb = 1,4-bis-(diphenylphosphino)butane), as well as the mechanism of cell death induction that occurs against murine sarcoma-180 tumor. Thus, MTT assay was applied to assess the ruthenium cytotoxicity, showing that the compound is a more potent inhibitor for the sarcoma-180 tumor cell viability than normal cells (lymphocytes). The comet assay indicated low genotoxic for normal cells. cis-[RuCl(BzCN)(phen)(dppb)]PF6 also showed moderate lethality in Artemia salina. The complex induced cell cycle arrest in the G0/G1 phase in sarcoma-180 cells. In addition, the complex caused S180 cells to die by apoptosis by an increase in Annexin-V-positive cells and morphological changes typical of apoptotic cells. Additionally, cis-[RuCl(BzCN)(phen)(dppb)]PF6 increased the gene expression of Bax, Casp3, and Tp53 in S180 cells. By using a western blot, we observed an increased protein level of TNF-R2, Bax, and p21. In conclusion, cis-[RuCl(BzCN)(phen)(dppb)]PF6 is active and selective for sarcoma-180 cells, leading to cell cycle arrest at the G0/G1 and cell death through a caspases-mediated and Tp53/p21-mediated pathway.

Antimicrobial activity of Calendula officinalis, Camellia sinensis and chlorhexidine against the adherence of microorganisms to sutures after extraction of unerupted third molars.

OBJECTIVE: The objective of this study was to compare the antimicrobial effect of mouthwashes containing Calendula officinalis L., Camellia sinensis (L.) Kuntze and 0.12% chlorhexidine digluconate on the adherence of microorganisms to suture materials after extraction of unerupted third molars. MATERIAL AND METHODS: Eighteen patients with unerupted maxillary third molars indicated for extraction were selected (n=6 per mouthwash). First, the patients were subjected to extraction of the left tooth and instructed not to use any type of antiseptic solution at the site of surgery (control group). After 15 days, the right tooth was extracted and the patients were instructed to use the Calendula officinalis, Camellia sinensis or chlorhexidine mouthwash during 1 week (experimental group). For each surgery, the sutures were removed on postoperative day 7 and placed in sterile phosphate-buffered saline. Next, serial dilutions were prepared and seeded onto different culture media for the growth of the following microorganisms: blood agar for total microorganism growth; Mitis Salivarius bacitracin sucrose agar for mutans group streptococci; mannitol agar for Staphylococcus spp.; MacConkey agar for enterobacteria and Pseudomonas spp., and Sabouraud dextrose agar containing chloramphenicol for Candida spp. The plates were incubated during 24-48 h at 37ºC for microorganism count (CFU/mL). RESULTS: The three mouthwashes tested reduced the number of microorganisms adhered to the sutures compared to the control group. However, significant differences between the control and experimental groups were only observed for the mouthwash containing 0.12% chlorhexidine digluconate. CONCLUSIONS: Calendula officinalis L. and Camellia sinensis (L.) Kuntze presented antimicrobial activity against the adherence of microorganisms to sutures but were not as efficient as chlorhexidine digluconate.

Antimicrobial activity of Calendula officinalis, Camellia sinensis and chlorhexidine against the adherence of microorganisms to sutures after extraction of unerupted third molars

OBJECTIVE: The objective of this study was to compare the antimicrobial effect of mouthwashes containing Calendula officinalis L., Camellia sinensis (L.) Kuntze and 0.12 percent chlorhexidine digluconate on the adherence of microorganisms to suture materials after extraction of unerupted third molars. MATERIAL AND METHODS: Eighteen patients with unerupted maxillary third molars indicated for extraction were selected (n=6 per mouthwash). First, the patients were subjected to extraction of the left tooth and instructed not to use any type of antiseptic solution at the site of surgery (control group). After 15 days, the right tooth was extracted and the patients were instructed to use the Calendula officinalis, Camellia sinensis or chlorhexidine mouthwash during 1 week (experimental group). For each surgery, the sutures were removed on postoperative day 7 and placed in sterile phosphate-buffered saline. Next, serial dilutions were prepared and seeded onto different culture media for the growth of the following microorganisms: blood agar for total microorganism growth; Mitis Salivarius bacitracin sucrose agar for mutans group streptococci; mannitol agar for Staphylococcus spp.; MacConkey agar for enterobacteria and Pseudomonas spp., and Sabouraud dextrose agar containing chloramphenicol for Candida spp. The plates were incubated during 24-48 h at 37ºC for microorganism count (CFU/mL). RESULTS: The three mouthwashes tested reduced the number of microorganisms adhered to the sutures compared to the control group. However, significant differences between the control and experimental groups were only observed for the mouthwash containing 0.12 percent chlorhexidine digluconate. CONCLUSIONS: Calendula officinalis L. and Camellia sinensis (L.) Kuntze presented antimicrobial activity against the adherence of microorganisms to sutures but were not as efficient as chlorhexidine digluconate.

Antimicrobial photodynamic therapy in rat experimental candidiasis: evaluation of pathogenicity factors of Candida albicans.

OBJECTIVE: This study evaluated the effects of photodynamic therapy on pathogenicity of Candida albicans. STUDY DESIGN: Fifty-six rats were submitted to development of candidiasis on the tongue dorsum by C. albicans inoculations. After 5 days, different treatments were administered: laser and photosynthesizer methylene blue (L+P+); laser only (L+P-); photosensitizer only (L-P+); and physiologic solution only (L-P-). Samples of the oral cavity were collected for a count of colony-forming units per mL. Colonies were isolated for evaluation of proteinase and phospholipase activities. The rats were killed for microscopic analysis of the tongue dorsum. The data were analyzed by analysis of variance, Kruskal-Wallis, and Bonferroni tests. RESULTS: The number of C. albicans recovered from the oral cavity of the rats was similar between the groups (P = .106). The L+P+ group showed fewer microscopic lesions of candidiasis than the L-P- group (P = .001). The L+P+ group presented lower proteinase activity compared with the other groups, with significant difference between the groups L+P+ and L-P+ (P = .018). CONCLUSIONS: Photodynamic therapy reduced the microscopic lesions of experimental candidiasis in rats and inhibited the proteinase activity of C. albicans.

Photodynamic therapy for the treatment of buccal candidiasis in rats.

The study objective was to evaluate the effects of photodynamic therapy on buccal candidiasis in rats. After experimental candidiasis had been induced on the tongue dorsum, 72 rats were distributed into four groups according to treatment: treated with laser and methylene blue photosensitizer (L+P+); treated only with laser (L+P-); treated only with photosensitizer (L--P+); not treated with laser or photosensitizer (L-P-). The rats were killed immediately, 1 day, or 5 days after treatment, for microscopic analysis of the tongue dorsum. Observation verified that the photodynamic therapy group (L+P+) exhibited fewer epithelial alterations and a lower chronic inflammatory response than the L-P- group. The group L+P- presented more intense epithelial alterations and chronic inflammatory response than the remaining groups. The L-P+ group showed tissue lesions similar to those of the L-P- group. In conclusion, rats treated with photodynamic therapy developed more discrete candidiasis lesions than did the remaining groups.

[Birth weight as predictor for the severity of neonatal brain white matter lesion]. / Peso de nascimento como preditor para a gravidade da lesão da substância branca cerebral neonatal.

To analyze the association of natal factors with the severity of neonatal brain white matter lesion (WML) by controlling the birth weight, we identified newborns with WML who were divided into: those with WML evolution towards resolution of the ultrasound image (less severe), and those who evolved with cist formation and/or ventriculomegalia and/or hemorrhage (greater severity). There were differences among the twelve variables (hyponatremia, anemia, infection, retinopathy, broncopulmonary dysplasia, hypoalbuminemia, persistence of the arterial canal, altered audiometry, early respiratory distress, birth weigh below 2,500 g, weight per category, and prematurity) between the two groups (p<0.05), being that nine variables (hyponatremia, infection, retinopathy, hypoalbuminemia, persistence of the arterial canal, early respiratory distress, low weight, prematurity, and weight per category) remained statistically different (p<0.01) after the logistic regression analysis. When the variables were analyzed by birth weight category none of them presented statistical significance. This study suggests that birth weight is the major factor--likely the only one--associated to the severity of neonatal brain white matter lesion.

Brain white matter lesions correlated to newborns death and lethality

OBJECTIVES: to describe hospital lethality rates and factors correlated to death in neonates with brain white matter lesions. METHODS: a retrospective study was performed from January 1994 to December 2001. Neonates with white brain matter lesions were divided into survival and death groups and their medical files reviewed through the single blind method to determine evolution. Death certificates provided the cause of death. The groups were compared through correlation coefficients. Hospital lethality rate was calculated. RESULTS: ninety three cases of white brain matter lesions and seven deaths were determined. Hospital lethality rate was of 8.2. percent (95 percentCI: 2.4-14.0) independently from lesion occurrence time, and of 10.3 percent (95 percentCI: 3.3-17.3) for deaths occurred during prenatal and perinatal periods. Death was correlated to: Apgar score, non-cephalic presentation, gestational age, hyperglicemia, hypercalcemia, convulsion, respiratory insufficiency and atelectasy. CONCLUSIONS: hospital lethality was of 10.3 percent generating the following hypothesis: perinatal asphyxia must be the principal direct and indirect etiologic factor (aggravating the expression of prematurity and infection diseases), of prenatal and perinatal mortality among newborns with white brain matter lesions; and <7 Apgar score in the 5th minute associated to brain white matter lesions, are markers for perinatal asphyxia diagnosis.

OBJETIVOS: descrever a taxa de letalidade hospitalar e fatores correlacionados com o óbito em crianças com lesão da substância branca cerebral (LSB). MÉTODOS: estudo retrospectivo realizado de janeiro de 1994 a dezembro de 2001. Os neonatos com LSB foram divididos em sobreviventes ou óbito, e seus prontuários revisados de forma cega para a evolução. Dos atestados de óbito, a causa de morte. Os grupos foram comparados por coeficientes de correlação. Calculada a taxa de letalidade hospitalar. RESULTADOS: foram encontrados 93 casos de LSB e sete óbitos. A taxa de letalidade hospitalar foi de 8,2 por cento, (IC95 por cento: 2,4-14,0), independentemente da época de instalação da lesão, e de 10,3 por cento (IC95 por cento: 3,3-17,3) para aqueles de ocorrência pré/perinatal. O óbito correlacionou-se com: escore de Apgar, apresentação não-cefálica, idade gestacional, hiperglicemia, hipercalcemia, convulsão, insuficiência respiratória e atelectasia. CONCLUSÕES: a letalidade hospitalar foi de 10,3 por cento e as seguintes hipóteses foram geradas: a asfixia perinatal deve ser o principal fator etiológico, direto e indireto (agravando a expressão das doenças da prematuridade e da infecção), da mortalidade pré/perinatal entre neonatos com LSB; e o escore de Apgar do 5o minuto <7, associado à LSB, são marcadores para o diagnóstico de asfixia perinatal.

Contingência e contigüidade: efeitos paramétricos do esquema de tempo variável sobre o responder em ratos / Contingency and contiguity: parametrical effects of variable-time schedule on the responding of rats

O objetivo deste estudo foi analisar como o responder, mantido sob esquema de VI, seria afetado ao ser submetido a diferentes valores de VT e extinção. Oito ratas foram expostas a sessões de linha de base em VI 20 s e, na seqüência, a sessões de VT 10 s, VT 20 s e VT 40 s (em ordem crescente ou decrescente) seguidas, finalmente, por uma sessão final de extinção da resposta de pressão à barra, cada uma delas antecipada por uma condição de re-treino em VI 20 s. Os resultados não revelaram efeitos paramétricos sistemáticos do esquema de VT 20 s sobre o responder, mas, para a maioria dos sujeitos, o esquema de VT 10 s, à semelhança da extinção, produziu taxas de resposta menores do que VT 40 s, a despeito da freqüência maior de acionamentos do bebedouro em VT 10 s. Os dados sugerem que o menor número de intervalos contíguos e curtos entre acionamentos consecutivos do bebedouro pode ajudar a compreender a relação inversa observada entre as taxas de respostas e os valores dos esquemas independentes de resposta.(AU)

The experiment aimed at analyzing how responding maintained by VI schedule would be affected when it was subsequently exposed to different values of VT and extinction. Eight female rats were initially exposed to baseline sessions in which lever presses operated a water dispenser on a VI-20-s schedule. Afterward, subjects were exposed to sessions of VT 10 s, VT 20 s, and VT 40 s (in either an increasing or a decreasing sequence) followed by a final extinction session, each of them initiated by a retraining condition on VI. Results did not demonstrate effects of VT 20 s over response rates. However, for most subjects, the VT 10 s, as well as extinction, generated lower response rates than VT 40 s, despite the higher frequency of water presentations on VT 10 s. Results suggest that the more numerous and shorter intervals between two consecutive water presentations may contribute to the understanding of this inverse relation involving response rates and the values of the response-independent schedules.(AU)

Peso de nascimento como preditor para a gravidade da lesão da substância branca cerebral neonatal / Birth weight as predictor for the severity of neonatal brain white matter lesion

Para analisar a associação entre fatores natais com a gravidade da lesão da substância branca (LSB) cerebral neonatal, controlando o peso de nascimento, identificaram os neonatos pela ultra-sonografia craniana, que foram divididos em: aqueles com evolução da LSC para resolução da imagem ao ultra-som (menor gravidade) e, aqueles que evoluiram com formação de cistos e/ou ventriculomegalia e/ou hemorragia (maior gravidade). Doze variáveis (hiponatremia, anemia, infecção, retinopatia, displasia broncopulmonar, hipoalbuminemia, persistência do canal arterial, audiometria alterada, desconforto respiratório precoce, peso de nascimento <2500g, peso por categoria e prematuridade) tiveram diferenças entre os dois grupos (p<0,05), sendo que 9 (hiponatremia, infecção, retinopatia, hipoalbuminemia, persistência do canal arterial, desconforto respiratório precoce, baixo peso, prematuridade e peso por categorias) se mantiveram estatisticamente diferentes (p<0,01) após análise por regressão logística. Quando analisadas por categoria de peso de nascimento, nenhuma variável demonstrou significância estatística. O estudo sugere que o peso de nascimento é o maior fator - provavelmente o único - associado com gravidade da LSB cerebral neonatal.