The role of GAPDH in the selective toxicity of CNP in melanoma cells.

BACKGROUND: Malignant melanoma is the most aggressive form of skin cancer with a rather poor prognosis. Standard chemotherapy often results in severe side effects on normal (healthy) cells finally being difficult to tolerate for the patients. Shown by us earlier, cerium oxide nanoparticles (CNP, nanoceria) selectively killed A375 melanoma cells while not being cytotoxic at identical concentrations on non-cancerous cells. In conclusion, the redox-active CNP exhibited both prooxidative as well as antioxidative properties. In that context, CNP induced mitochondrial dysfunction in the studied melanoma cells via generation of reactive oxygene species (primarily hydrogen peroxide (H2O2)), but that does not account for 100% of the toxicity. AIM: Cancer cells often show an increased glycolytic rate (Warburg effect), therefore we focused on CNP mediated changes of the glucose metabolism. RESULTS: It has been shown before that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) activity is regulated via oxidation of a cysteine in the active center of the enzyme with a subsequent loss of activity. Upon CNP treatment, formation of cellular lactate and GAPDH activity were significantly lowered. The treatment of melanoma cells and melanocytes with the GAPDH inhibitor heptelidic acid (HA) decreased viability to a much higher extent in the cancer cells than in the studied normal (healthy) cells, highlighting and supporting the important role of GAPDH in cancer cells. CONCLUSION: We identified glyceraldehyde 3-phosphate dehydrogenase (GAPDH) as a target protein for CNP mediated thiol oxidation.

Metabolic effects of SGLT2i and metformin on 3-hydroxybutyric acid and lactate in db/db mice.

Combining a Sodium-Glucose-Cotransporter-2-inhibitor (SGLT2i) with metformin is recommended for managing hyperglycemia in patients with type 2 diabetes (T2D) who have cardio-renal complications. Our study aimed to investigate the metabolic effects of SGLT2i and metformin, both individually and synergistically. We treated leptin receptor-deficient (db/db) mice with these drugs for two weeks and conducted metabolite profiling, identifying 861 metabolites across kidney, liver, muscle, fat, and plasma. Using linear regression and mixed-effects models, we identified two SGLT2i-specific metabolites, X-12465 and 3-hydroxybutyric acid (3HBA), a ketone body, across all examined tissues. The levels of 3HBA were significantly higher under SGLT2i monotherapy compared to controls and were attenuated when combined with metformin. We observed similar modulatory effects on metabolites involved in protein catabolism (e.g., branched-chain amino acids) and gluconeogenesis. Moreover, combination therapy significantly raised pipecolate levels, which may enhance mTOR1 activity, while modulating GSK3, a common target of SGLT2i and 3HBA inhibition. The combination therapy also led to significant reductions in body weight and lactate levels, contrasted with monotherapies. Our findings advocate for the combined approach to better manage muscle loss, and the risks of DKA and lactic acidosis, presenting a more effective strategy for T2D treatment.

Shikonin reverses cancer-associated fibroblast-induced gemcitabine resistance in pancreatic cancer cells by suppressing monocarboxylate transporter 4-mediated reverse Warburg effect.

BACKGROUND: Gemcitabine is a first-line chemotherapeutic agent for pancreatic cancer (PC); however, most patients who receive adjuvant gemcitabine rapidly develop resistance and recurrence. Cancer-associated fibroblasts (CAFs) are a crucial component of the tumor stroma that contribute to gemcitabine-resistance. There is thus an urgent need to find a novel therapeutic strategy to improve the efficacy of gemcitabine in PC cells under CAF-stimulation. PURPOSE: To investigate if shikonin potentiates the therapeutic effects of gemcitabine in PC cells with CAF-induced drug resistance. METHODS: PC cell-stimulated fibroblasts or primary CAFs derived from PC tissue were co-cultured with PC cells to evaluate the ability of shikonin to improve the chemotherapeutic effects of gemcitabine in vitro and in vivo. Glucose uptake assay, ATP content analysis, lactate measurement, real-time PCR, immunofluorescence staining, western blot, and plasmid transfection were used to investigate the underlying mechanism. RESULTS: CAFs were innately resistant to gemcitabine, but shikonin suppressed the PC cell-induced transactivation and proliferation of CAFs, reversed CAF-induced resistance, and restored the therapeutic efficacy of gemcitabine in the co-culture system. In addition, CAFs underwent a reverse Warburg effect when co-cultured with PC cells, represented by enhanced aerobic glycolytic metabolism, while shikonin reduced aerobic glycolysis in CAFs by reducing their glucose uptake, ATP concentration, lactate production and secretion, and glycolytic protein expression. Regarding the mechanism underlying these sensitizing effects, shikonin suppressed monocarboxylate transporter 4 (MCT4) expression and cellular membrane translocation to inhibit aerobic glycolysis in CAFs. Overexpression of MCT4 accordingly reversed the inhibitory effects of shikonin on PC cell-induced transactivation and aerobic glycolysis in CAFs, and reduced its sensitizing effects. Furthermore, shikonin promoted the effects of gemcitabine in reducing the growth of tumors derived from PC cells and CAF co-inoculation in BALB/C mice, with no significant systemic toxicity. CONCLUSION: These results indicate that shikonin reduced MCT4 expression and activation, resulting in inhibition of aerobic glycolysis in CAFs and overcoming CAF-induced gemcitabine resistance in PC. Shikonin is a promising chemosensitizing phytochemical agent when used in combination with gemcitabine for PC treatment. The results suggest that disrupting the metabolic coupling between cancer cells and stromal cells might provide an attractive strategy for improving gemcitabine efficacy.

Baicalin and N-acetylcysteine regulate choline metabolism via TFAM to attenuate cadmium-induced liver fibrosis.

(Background): Cadmium is an environmental pollutant associated with several liver diseases. Baicalin and N-Acetylcysteine have antioxidant and hepatoprotective effects. (Purpose): However, it is unclear whether baicalin and N-Acetylcysteine can alleviate Cadmium -induced liver fibrosis by regulating metabolism, or whether they exert a synergistic effect. (Study design): We treated Cadmium-poisoned mice with baicalin, N-Acetylcysteine, or baicalin+ N-Acetylcysteine. We studied the effects of baicalin and N-Acetylcysteine on Cadmium-induced liver fibers and their specific mechanisms. (Methods): We used C57BL/6 J mice, and AML12, and HSC-6T cells to establish in vitro assays and in vivo models. (Results): Metabolomics was used to detect the effect of baicalin and N-Acetylcysteine on liver metabolism, which showed that compared with the control group, the Cadmium group had increased fatty acid and amino acid levels, with significantly reduced choline and acetylcholine contents. Baicalin and N-Acetylcysteine alleviated these Cadmium-induced metabolic changes. We further showed that choline alleviated Cadmium -induced liver inflammation and fibrosis. In addition, cadmium significantly promoted extracellular leakage of lactic acid, while choline alleviated the cadmium -induced destruction of the cell membrane structure and lactic acid leakage. Western blotting showed that cadmium significantly reduced mitochondrial transcription factor A (TFAM) and Choline Kinase α(CHKα2) levels, and baicalin and N-Acetylcysteine reversed this effect. Overexpression of Tfam in mouse liver and AML12 cells increased the expression of CHKα2 and the choline content, alleviating and cadmium-induced lactic acid leakage, liver inflammation, and fibrosis. (Conclusion): Overall, baicalin and N-Acetylcysteine alleviated cadmium-induced liver damage, inflammation, and fibrosis to a greater extent than either drug alone. TFAM represents a target for baicalin and N-Acetylcysteine, and alleviated cadmium-induced liver inflammation and fibrosis by regulating hepatic choline metabolism.

Podem as bactérias ácido lácticas probióticas apresentarem efeito antitumoral em modelo animal de câncer de cólon? Uma revisão da literatura / Can probiotic acid lactic bacteria submit antitumor effect in animal model of colon cancer? A review of the literature

O Câncer de cólon é um dos tipos mais comuns de câncer no mundo e a segunda principal causa de morte relacionada a esta doença em países desenvolvidos. Até 75% dos casos estão associados com a alimentação, indicando que uma pessoa pode reduzir o seu risco simplesmente através de modificação na dieta. Estudos em animais demonstram que várias cepas de bactérias ácido lácticas protegem contra o câncer de cólon em roedores, embora os dados em humanos sejam limitados e conflitantes. O objetivo deste estudo foi investigar a eficácia das bactérias ácido lácticas no tratamento e redução do câncer de cólon em modelo animal. Foram realizadas buscas sistemáticas em bases de dados eletrônicas alcançando 1079 artigos relacionados, entretanto apenas 6 artigos foram eleitos de acordo com os critérios de elegibilidade para análise. Todos os artigos avaliados apresentaram resultados satisfatórios quanto à inibição do câncer de cólon em ratos e camundongos ao utilizarem cepas predominantemente do gênero Lactobacillus. Este estudo pode responder a hipótese de que as bactérias ácido lácticas apresentam efeito preventivo e antitumoral contra o câncer de cólon.(AU)

Colon cancer is one of the most common types of cancer in the world and the second leading cause of death related to the disease in developed countries. Up to 75% of cases are associated with eating, indicating that a person can reduce their risk simply through dietary modification. Studies in animals show that various strains of lactic acid bacteria protect against colon cancer in rodents although data in humans are limited and conflicting. The aim of this study was to investigate the efficacy of acid lactic bacteria in the treatment and reduction of colon cancer in animal models. Systematic searches were conducted in electronic databases reaching 1079 related articles, only six articles were elected according instead of to the eligibility criteria for analysis. All reviewed articles showed satisfactory results on the inhibition of colon cancer in rats and mice when using predominantly Lactobacillus strains. This study can answer hypothesis that acid lactic bacteria has antitumor effect against colon cancer.(AU)

El ácido láctico y la escala SEGRAV-23 como valores pronósticos de gravedad en niños críticos / Lactic acid and SEGRAV-23 scale as predictive values of severity in critically-ill children

INTRODUCCIÓN: los sistemas de valoración de la gravedad son medios para cuantificar objetivamente la situación clínica del paciente, determinar el pronóstico y evaluar la eficacia y eficiencia del tratamiento. El lactato es un biomarcador que ha demostrado su magnífica capacidad predictiva de mortalidad, lo que hace que se mantenga dentro de las recomendaciones de expertos y en todas las guías relevantes. OBJETIVO: determinar el pronóstico de gravedad del ácido láctico y del índice Sistema para evaluar la gravedad de las enfermedades (SEGRAV-23), en niños ingresados en la Unidad de Cuidados Intensivos Pediátricos en el periodo febrero de 2011 a febrero de 2013. MÉTODOS: se realizó un estudio observacional, analítico, longitudinal y prospectivo en el cual se estudiaron 208 pacientes ingresados en las unidades de cuidados intensivos pediátricos de los hospitales "Dr. Luis Díaz Soto" y "Juan Manuel Márquez", en el periodo de febrero de 2011 a febrero de 2013. Para determinar el grado de dependencia entre vivos y fallecidos en el índice SEGRAV-23 y los valores del lactato, se utilizó el chi cuadrado de Pearson con una p menor de 0,05 para garantizar una confiabilidad de un 95 %. RESULTADOS: con respecto al SEGRAV-23 y los valores de lactato se observó que el 32,3 % de los pacientes con lactato entre 5-7 mmol/L se mantuvo con el reporte de muy graves, y el 14,7 % críticos. El 43,7 % de los fallecidos presentaron SEGRAV-23 mayor de 21 puntos. El 35,3 % de los pacientes que presentaron cifras de lactato al ingreso entre 5-7 mmol/L fallecieron. A los 10 días de estadía se evidenció que el 72,7 % de los pacientes que presentaron cifras de lactato entre 5-7 mmol/L fallecieron, al igual que el 80 % de los que tuvieron una hiperlactoacidemia mayor de 7 mmol/L. CONCLUSIONES: el ácido láctico y la escala SEGRAV-23 tienen una aceptable capacidad pronóstica y son buenos indicadores de gravedad del paciente crítico.

INTRODUCTION: the severity scoring systems are means to objectively quantify the patient's clinical situation, to determine the prognosis and to evaluate the efficacy and efficiency of the treatment. Lactate is a biomarker that has demonstrated its great predictive capacity for mortality, which keeps it included in the experts' recommendation and in all relevant guidelines. OBJECTIVE: to determine the severity prognosis of the lactic acid and of the index System for Evaluating the Severity of Diseases (SEGRAV-23) in children admitted to the pediatric intensive care unit in the period of February 2011 to February 2013. METHODS: prospective, longitudinal, analytical and observational study of 208 patients admitted to the pediatric intensive care units in "Dr Luis Diaz Soto" and "Juan Manuel Márquez" hospitals, conducted from February 2011 to February 2013. For the purpose of determining the level of dependence between the living and dead people in the SEGRAV-23 index and the lactate values, Pearson's chi square with p< 0.05 was used to assure 95 % reliability. RESULTS: regarding SEGRAV-23 and the lactate values, it was observed that 32.3 % of patients with 5-7 mmol/L lactate continued to be reported as severely-ill and 14.7 % as critical patients. In the group of dead people, 43.7 % had a SEGRAV-23 index higher than 21 scores whereas 35.3 % of patients with lactate values of 5 to 7 mmol/L on admission died. After ten days of hospitalization, it was evinced that 72.7 % of patients who had 5-7 mmol/L lactate values died as it happened with 80 % of those with over 7 mmol/L hyperlactoacidemia. CONCLUSIONS: lactic acid and the SEGRAV-23 scale have acceptable prognostic capacity and are good severity indicators in critically-ill patients.

Efeito alcalinizante da solução de Ringer com lactato em ovelhas sadias e acidóticas / Alkalinizing effect of lactated Ringer's solution in healthy and acidotic sheep

O estudo teve o objetivo de testar a hipótese de que o efeito alcalinizante da solução de Ringer com lactato (SRL) pode ser maior nos animais portadores de acidose metabólica do que nos sadios, como consequência da necessidade de retorno ao equilíbrio. Seis ovelhas receberam a SRL em volume correspondente a 10% do peso corporal, administrada por infusão contínua intravenosa, durante quatro horas, em duas condições definidas: enquanto eram saudáveis e após a indução experimental de acidose láctica ruminal aguda (ALRA). Amostras de sangue venoso e de urina foram colhidas em quatro momentos: antes do início da infusão, na metade do volume infundido, ao término da infusão e duas horas após. Foram determinados valores de pH sanguíneo e urinário, de pCO2, HCO3 - e BE no sangue, de Na+, K+, Cl-, SID, AG, PPT, Atot e lactato L no plasma, e das excreções fracionadas urinárias de Na+, K+, Cl- e lactato L. A SRL provocou hemodiluição, mas não interferiu nos equilíbrios eletrolítico e acidobase das ovelhas sadias. Apesar de eficaz para reverter a desidratação, não foi capaz de corrigir a acidose metabólica presente após a indução da ALRA.

The aim of this study was to investigate if the alkalinizing effect of lactated Ringer's solution (LRS) is greater in animals with metabolic acidosis than in healthy ones, as a result of the need to restore acid-base balance. LRS was intravenously infused in a volume corresponding to 10% of body weight, continously during four hours, in two definite conditions in the same six ewes: when they were healthy and after experimentally induced acute rumen lactic acidosis (ARLA). Venous blood and urine samples were taken in four moments: before the beginning, in the middle, at the end of the infusion and two hours after. Blood and urine pH, blood pCO2, HCO3 - and BE, and plasma Na+, K+, Cl-, TP and L lactate were measured. Na+, K+, Cl- and L lactate fractional clearance and plasma SID, AG, and Atot were calculated. LRS caused hemodilution but didn't change electrolyte and acid-base balances in healthy ewes. When ewes were affected by ARLA, the infusion of this solution was effective for dehydration reversion but was unable to correct metabolic acidosis.

The use of vancomycin-loaded poly-l-lactic acid and poly-ethylene oxide microspheres for bone repair: an in vivo study

OBJECTIVE: The aim of this study was to investigate bone repair after the implantation of vancomycin-loaded poly-L-lactic acid/poly-ethylene oxide microspheres compared with vancomycin-unloaded poly-L-lactic acid/poly-ethylene oxide microspheres. METHODS: Poly-L-lactic acid/poly-ethylene oxide microspheres were implanted in rat tibiae and evaluated for periods of 2, 4, 8, and 12 days and 4, 8, 16, and 32 weeks. The groups implanted with vancomycin-loaded and vancomycin-unloaded microspheres were compared. Histopathologic (semi-quantitative) and histomorphometric analyses were performed to evaluate the bone formation process. RESULTS: During the first period (second day), fibrin and hemorrhaging areas were observed to be replaced by granulation tissue around the microspheres. Woven bone formation with progressive maturation was observed. All of the histopathological findings, evaluated by a semi-quantitative assay and a quantitative analysis (percentage of bone formation), were similar between the two groups. CONCLUSION: Vancomycin-loaded poly-L-lactic acid/poly-ethylene oxide microspheres are a good bone substitute candidate for bone repair. Local antibiotic therapy using vancomycin-loaded poly-L-lactic acid/poly-ethylene oxide microspheres should be considered after the microbiological evaluation of its efficacy.

Combination of poly L-lactic acid nanofiber scaffold with omentum graft for bone healing in experimental defect in tibia of rabbits / Combinação de poli L-ácido láctico nanofibras com enxerto de omento para reparo ósseo em defeito experimental em tíbia de coelhos

PURPOSE: To investigate the osteoconductive properties and biological performance of Poly L-lactic acid (PLLA) with omentum in bone defects. METHODS: PLLA nanofiber scaffolds were prepared via electrospinning technique. Forty four New Zealand white female rabbits randomly divided into three groups of 18 rabbits each. Created defects in right tibias were filled in group I with omentum, in group II with PLLA nanofiber scaffold and in group III with combination of the omentum and PLLA. The same defects were created in left tibia of all groups but did not receive any treatment (control group). Histological and histomorphometric evaluations were performed at two, four and six weeks after the implantation. RESULTS: Histological changes on all groups along with the time course were scored and statistical analysis showed that the average scores in group III were significantly higher than the other groups. CONCLUSION: Histomorphometric analysis of bone healing was shown to be significantly improved by the combined PLLA with omentum compared with the other groups, suggesting this biomaterial promote the healing of cortical bone, presumably by acting as an osteoconductive scaffold.

OBJETIVO: Investigar as propriedades de osteocondução e desempenho biológico do ácido L láctico-Poly (PLLA) com omento em defeitos ósseos. MÉTODOS: Andaimes PLLA nanofibras foram preparados via eletrofiação técnica. Cinquenta e quatro coelhos fêmeas Nova Zelândia brancos foram distribuídos aleatoriamente em três grupos de 18 coelhos cada. Defeitos criados em tíbias direitas foram preenchidos no grupo I com omento, no grupo II com PLLA nanofibras e no grupo III com a combinação do omento e PLLA. Os mesmos defeitos foram criados na tíbia esquerda de todos os grupos, mas não receberam qualquer tratamento (grupo controle). As avaliações histológicas e histomorfométricas foram realizadas em duas, quatro e seis semanas após a implantação. RESULTADOS: As alterações histológicas em todos os grupos, juntamente com o curso de tempo foram marcados e análise estatística mostrou que as pontuações médias do grupo III foram significativamente mais elevadas do que os outros grupos. CONCLUSÃO: Análise histomorfométrica da cicatrização óssea mostrou-se significativamente melhor com o PLLA combinado com omento em comparação com os outros grupos, sugerindo que este biomaterial promove a cicatrização do osso cortical, provavelmente atuando como osteocondutor.

FisiograftTM as a bone material in the treatment of periodontal vertical defects and its clinical and radiological evaluation: clinical study / FisiograftTM como material de enxerto ósseo no tratamento de defeitos periodontais verticais e sua avaliação clínica e radiográfica: um estudo clínico

Objectives: The purpose of this clinical study is to determine the efficacy of Fisiograft™ as a bone graft materialin the treatment of three wall vertical defects in generalized chronic periodontitis patients and theirclinical and radiological evaluation. Materials and methods: Twenty patients (with 30 defects) diagnosedwith generalized chronic periodontitis having two or more three wall vertical defects were selected for thisstudy. Clinical parameters like plaque index, gingival index, probing pocket depth and clinical attachmentlevels were recorded at different points of time over six months. Radiographic evaluation included the depthof the bone defect and the percentage of bone defect fill, and was carried out for both the groups at baseline,three months and six months. After recording clinical parameters and administering phase-1 therapy, thesites were randomly treated either with Fisiograft™ or open flap debridement only. Results: At the end of sixmonths there was a significant reduction in the plaque and gingival scores in both test and control groups.There was 64% decrease in probing pocket depth for the test site as compared to 55% decrease seen for thecontrol group. Similarly there was an 85% gain in clinical attachment level from the baseline to six monthspost operatively for the experimental group in comparison to 69% gain for the control group. Furthermore,44% bone fill was observed for the experimental site whereas only 18% of bone fill was evident in the controlsite. Conclusion: Fisiograft™ improves healing outcomes, leads to a reduction of probing depth, a resolutionof osseous defects and a gain in clinical attachment, compared with open flap debridement by itself.

Objetivo: O objetivo do presente estudo clínico foi determinar a eficácia do Fisiograft®, como material de enxerto ósseo, no tratamento de defeitos ósseos verticais de três paredes em pacientes com periodontite crônica,bem como avaliações clínica e radiográfica. Materiais e métodos: Vinte pacientes (com 30 defeitos)diagnosticados com periodontite crônica generalizada, portando dois ou mais defeitos ósseos verticais detrês paredes foram selecionados para o estudo. Parâmetros clínicos como índice de placa, índice gengival,profundidade de bolsa à sondagem e níveis clínicos de inserção foram registrados em diferentes intervalos de tempo até seis meses. Avaliações radiográficas incluíram a profundidade do defeito ósseo e a porcentagem de preenchimento do defeito ósseo, sendo realizadas em ambos os grupos imediatamente (baseline),em três meses e seis meses. Após registrar os parâmetros clínicos e administrar a terapia de fase-1, os locais foram tratados aleatoriamente com Fisiograft® ou retalho de espessura total somente. Resultados: Ao fim do período de seis meses houve redução significativa nos índices de placa e gengival em ambos os grupos,controle e experimental. Houve redução de 64% na profundidade de bolsa à sondagem para os locais de teste comparado, 55% de redução no grupo controle. Similarmente, houve ganho de 85% no nível clínico de inserção do baseline para o período de seis meses de pós-operatório para o grupo experimental em comparação ao ganho de 69% para o grupo controle. Adicionalmente, um preenchimento ósseo de 44% foi observado para os locais experimentais, enquanto somente 18% de preenchimento foi evidente nos locais de controle.Conclusão: O Fisiograft® melhora os resultados de cicatrização, promove redução na profundidade de sondagem,constitui uma resolução para os defeitos ósseos e aumento na inserção clínica, comparado ao retalho de espessura total somente.

Use of a lactic acid plus lactoserum intimate liquid soap for external hygiene in the prevention of bacterial vaginosis recurrence after metronidazole oral treatment / Uso do ácido láctico com lactoserum em sabonete líquido íntimo para higiene externa na prevenção da recorrência de vaginose bacteriana após tratamento oral com metronidazol

OBJECTIVE: To determine the recurrence of bacterial vaginosis (BV) after the use of a lactic acid plus lactoserum liquid soap starting immediately after the treatment with oral metronidazole and the quality of life of the participants. METHODS: A total of 123 women with diagnosis of BV with at least three of the following criteria: 1) homogeneous vaginal discharge without inflammation of the vagina or vulva; 2) vaginal pH ≥ 4.5; 3) positive Whiff test; and 4) "clue cells" in more than 20 percent of the epithelial cells in the vagina. A Nugent score ≥ 4 in the vaginal bacterioscopy was also used. After BV diagnosis, metronidazole 500 mg was administered orally bid during 7 days. Patients cured of BV were then instructed to use 7.5 to 10 mL of a lactic acid plus lactoserum liquid soap once-a-day for hygiene of the external genital region. Three subsequent control visits after starting the hygiene treatment (30, 60, and 90 days; ± 5 days) were scheduled. A questionnaire was applied in the form of visual analogue scale (VAS) in all the visits regarding: 1) level of comfort at the genital region; 2) malodorous external genitalia; 3) comfort in sexual intercourse; 4) satisfaction with intimate hygiene; and 5) self-esteem. RESULTS: Ninety two (74.8 percent) women initiated the use of a lactic acid plus lactoserum liquid soap at visit 1. At visit 2, 3, and 4 there were 84, 62 and 42 women available for evaluation, respectively. The rate of recurrence of BV was 19.0 percent, 24.2 percent and 7.1 percent, respectively in the three visits and vaginal candidiasis was observed in five treated women. Quality of life was evaluated in the 42 women who completed the four visits schedule and there were significant improvement in the five domains assessed. CONCLUSION: A lactic acid plus lactoserum liquid soap for external intimate hygiene may be an option for the prevention of BV recurrence after treatment and cure with oral metronidazole.

OBJETIVO: Determinar a ocorrência de vaginose bacteriana (VB) após o uso de acido láctico com lactoserum em sabonete líquido iniciado imediatamente após o tratamento com metronidazol oral e qualidade de vida das participantes. MÉTODOS: Um total de 123 mulheres com dianóstico de VB com ao menos três dos seguintes critérios: 1) leucorreia vaginal homogênea sem inflamação de vagina ou vulva; 2) pH vaginal ≥ 4,5; 3) teste positivo de Whiff; e 4) "clue cells" em mais de 20 por cento das células epiteliais na vagina. O escore de Nugent ≥ 4 na bacterioscopia vaginal também foi usado. Após o diagnóstico de VB, metronidazol 500 mg oral foi ministrado durante 7 dias. Pacientes curados da VB foram instruídos a usar 7,5 a 10 mL de acido láctico com lactoserum em sabonete líquido uma vez ao dia para higiene da genitália externa. Três visitas de controle foram agendadas (30, 60 e 90 dias; ± 5 dias). Um questionário foi aplicado na forma de escala visual análoga (EVA) em todas as visitas sobre: 1) nível de conforto na região genital; 2) mau odor na genitália; 3) conforto na relação sexual; 4) satisfação com higiene íntima; e 5) autoestima. RESULTADOS: Noventa e duas (74,8 por cento) mulheres iniciaram o uso de ácido láctico com lactoserum líquido na visita 1. Na visita 2, 3 e 4 foram 84, 62 e 42 mulheres para avaliação, respectivamente. A taxa de recorrência da VB foi 19,0 por cento, 24,2 por cento e 7,1 por cento, respectivamente nas três visitas e candidíase vaginal foi observada em cinco mulheres. Qualidade de vida foi avaliada em 42 mulheres que completaram as quatro visitas agendadas e houve uma melhora significativa nos cinco domínios avaliados. CONCLUSÃO: O uso de acido láctico com lactoserum em sabonete líquido para higiene externa intima pode ser uma opção para a prevenção da recorrência de VB após tratamento e cura com metronidazol oral.

Bioceramic/Poly (glycolic)-poly (lactic acid) composite induces mineralized barrier after direct capping of rat tooth pulp tissue

The aim of this study was to observe the histopathological pulp response following direct pulp capping of mechanically exposed teeth in rats with a composite of beta-tricalcium phosphate-hydroxyapatite bioceramic (BC) and poly (glycolic)-poly (lactic acid) (PLGA) material or a calcium hydroxide [Ca(OH)2] material, compared to BC alone and a negative control of water. Pulp of the maxillary molars was exposed, followed by capping with the experimental material. The pulpal tissue response was assessed post-operatively at 1, 7, 14 and 30 d, followed by histological analysis. The Ca(OH)2 group exhibited severe acute inflammatory cell infiltration at day 14. However after 30 d, a new hard tissue with macro porous obliteration of the pulp chamber and a characteristic necrotic area had appeared. BC and Ca(OH)2 capping were associated with moderate inflammation and dentinal bridge similar. Meanwhile, in the BC/PLGA composite group, there was moderate inflammatory infiltrate and formation of a dense and complete dentinal bridge. In conclusion, the BC/PLGA composite material showed a large zone of tertiary dentin, and effectively reorganized the dentin-pulp complex.

Uso de la jalea de aloe en la cervicitis aguda / Use of aloe gel in acute cervicitis

Se realiza un ensayo clínico a doble ciegas en un grupo de pacientes con cervicitis aguda, las cuales fueron atendidas en los policlínicos "Jorge Ruíz Ramírez" y "26 de Julio", del municipio Playa. Se analizaron diferentes síntomas y signos así como la respuesta al tratamiento con curas de aloe. Se concluye que el aloe es efectivo en el tratamiento de esta entidad y que se incrementan sus resultados favorables cuando se asocia con ácido láctico

DNA Vaccine for the Prevention and Treatment fo Tuberculosis

Tradicional systems for developing drugs and vaccines are failing spectaculary to deliver the goods in the fight against tuberculosis (TB). The disease that afflicts the developing world defies the imagination in its scale. One third of the world's population - 2 billion people - is infected with Mycobacterium tuberculosis, and 16 million have active TB. Shockingly, TB hit an all-time high in 1999 with 8 million new cases - 95 per cent of them in developing countries - and 2 million deaths. The disease is spreading rapidly throughout the world. The toll is set to rise; AIDS activates the dormant form of the disease, while multidrug resistance is spreading across the planet. The last new drug for TB was introduced over thirty years ago and industry has been reluctant to invest in discovering new families of drugs because of the financial risks in investing in products destined largely for developing country markets. If global health is left to market forces, historians will remember this era as one in which humanity stood idly by while half the planet languished in sickness. Fortunately some researchers have realized this, and are driving forward new models for TB therapy and vaccine discovery. One of the latest sign of this trend is the development of a DNA vaccine for the prevention and treatment of TB by our research group. Over the last few years, some of our experiments in wich mycobacterial antigens were presented to the immune system, as of they were viral antigens (DNA vaccine), have had a significant impact on our understanding of protective immunity against tuberculosis. They also markedly enhanced the prospects for new vaccines. We now know that individual mycobacterial-protein antigens expressed from DNA-vaccine constructs can confer protection equal to that from live BCG vaccine in mice. A critical determinant of the outcome of immunization appears to be the degree to which antigen-specific cytotoxic T cells are generated by the immune response. We have demonstrated that DNA vaccination is an affective way of establishing long lasting cytotoxic T-cell memory and protection against tuberculosis. Moreover, our new preclinical work shows that DNA vaccines, initially designed to prevent infection, can also have a dramatic therapeutic action. In infected mice, the immune response can be caused to switch from one that is relatively inefficient and gives bacterial stasis to one that kills the bacteria, eliminating...

Valor pronóstico de la velocidad de ascenso del ácido láctico plasmático en pacientes pediátricos sépticos: estudio prospectivo Hospital de Niños J. M. de Los Ríos Caracas / Hospital of children J.M. de los Ríos Caracas

Evaluar si la velocidad de ascenso en la concentración plasmática del ácido láctico (Alp) constituye un índice pronóstico útil en pacientes pediátricos con sepsis. Se determinó el Alp a las 0,12,24,36,48, y 60 horas ingreso de cada paciente incluidos en la investigación 30 días hasta 12 años. Unidad de Cuidados Intensivos (UCI) del Hospital J.M. de los Ríos. El Alp se determinó en el laboratorio general del Hospital Centro Médico de Caracas, utilizando un analizador TDx-FLx fabricado por Abbott Laboratories, N Chicago IL 60064. Se tomó una muestra de sangre (arterial o venosa) para dosificar el Alp. Valor normal del Alp 0,5-2,20 mMol/L. Se utilizó el índice de predicción pediátrica (IPP) para pacientes críticamente enfermos, comparándose éste con el Alp y la velocidad con que se modificaron en cada uno de los subgrupos de los pacientes estudiados. Se encontró correlación entre Alp, la velocidad con que la rata de producción del Alp se incrementa y la evolución clínica. A medida que la rata de producción del Alp es igual o mayor a 0,0474m/Mol/L/h mayor es la gravedad de la sepsis, con mayor número de muertes si ésta es igual o mayor a 0,098mMol/L/h. En total 19 pacientes sépticos fallecieron (47,5 por ciento) y 21 sobrevivieron (52,14 por ciento). La velocidad de ascenso en la concentración del Alp en pacientes pediátricos sépticos es un índice pronóstico útil para tomar decisiones terapéuticas más adecuadas

Avaliaçäo terapêutica do Malvatricin Ginecológico em processo inflamatório nas vulvites e vulvovaginites pré-puberal / Therapeutic evaluation of Malvatricin Ginecológico in infant patients with inflammatory disease in the genital tract

Dezessete pacientes com patologia inflamatória vulvovaginal foram acompanhados com Malvaticin Ginecológico em um estudo aberto, no sexo feminino, näo comparativo, no Estado do Rio de Janeiro, visando avaliar à eficácia e a telerância do fármaco, composto de Quinosol, Tirotricina, Ácido lático e Hidrolato de Malva. Demonstrou ser ificaz e com uma tolerância excelente em 100 por cento dos casos

Efeitos do lactato de amônio tópico sobre a atrofia cutânea causada por um corticosteróide tópico potente / Effects of topical ammonium lactate on cutaneous atrophy from a potent topical corticosteroid

Histórico: Os corticosteróides tópicos produzem alteraçöes atróficas na pele, inclusive diminuiçäo da espessura da epiderme e da substância essencial dérmica. Observamos que o lactato de amônio a 12 por cento produziu aumento da espessura da epiderme e aumento na qualidade de glicosaminoglicanos dérmicos. Objetivo: Determinar se o lactato de amônio a 12 por cento poderia minimizar a atrofia cutânea produzida por um corticosteróide tópico potente. Métodos: Ambos, o propionato de clobetasol e o lactato de amônio a 12 por cento, foram aplicados repetidas vezes sob patches oclusivos, bem como em patches abertos nos antebraços de voluntários durante 3 a 4 semanas. As amostras para biópsia foram avaliadas por análise de imagem quanto à espessura da epiderme e quanto à quantidade de glicosaminoglicanos dérmicos. Resultados: O lactato de amônio a 12 por cento atenuou significativamente a atrofia da epiderme e da derme sem nenhuma influência sobre a biodisponibilidade ou sobre as propriedades antiinflamatórias do corticosteróide. Conclusäo: O lactato de amônio a 12 por cento pode ser útil na atenuaçäo dos efeitos adversos do corticosteróide na pele

Principios fundamentales en regeneración ósea; su aplicación para implantes endoóseos: parte II / Fundamental principles in bone regeneration; its application for endoosseous implants: 2nd part

El presente y futuro de la ROG apuntan a la simplificación de la técnica utilizando membranas reabsorbibles y biomateriales que sustituyen el hueso autólogo, e intentando obtener los mismos resultados que con la técnica antes mencionada. Los límites de la implantología se están acabando con el advenimiento de este joven capítulo de ROG, cuyos objetivos reparador y restaurador del sistema incrementan en importancia debido al fracaso y la insuficiencia de los primeros niveles de prevención en nuestra odontología

Efeitos da loçäo de lactato de amônio a 12 por cento versus nenhum tratamento para a terapia da xerodermia plantar / The effects of ammonium lactate 12 per cents lotion versus no therapy in the treatment of dry skin of the heels

Sessenta indivíduos participaram de uma comparaçäo randomizada aberta, uni-cega (mascaramento do avaliador), bilateral e pareada. Alocou-se aleatoriamente uma formulaçäo de loçäo de lactato de amônio a 12 por cento ou nenhum tratameno à regiäo plantar direita ou esquerda. A loçäo foi aplicada duas vezes ao dia durante oito semanas no pé alocado, seguindo-se uma fase de regressäo de quatro semanas, na qual näo se aplicou o tratamento em nenhum dos pés. Os indivíduos apresentavam xerodermia plantar pelo menos moderada, igual em ambos os pés. Os que haviam aplicado medicaçöes com ou sem prescriçäo ou que haviam sido submetidos a debridamento mecânico nas duas semanas anteriores foram excluídos, bem como os que utilizaram retinóides orais no mês anterior ao início do estudo. A eficácia do tratamento näo pôde ser avaliada nos pacientes que utilizaram, durante o estudo, produtos tópicos nos pés que näo a medicaçäo pesquisada. Avaliou-se o efeito do lactato de amônio na pele da regiäo plantar, comparando-se sua eficácia à da ausência de tratamento através do "Overall Dryness Severity Score" (Escore de gravidade da xerodermia), "Physician Global Assessment of Improvement/Worsening" (avaliaçäo geral dos médicos de melhora/piora) e "Physician Preference" (preferência dos médicos). As avaliaçöes foram feitas na semana 0 (antes do tratamento) e nas semanas 1, 2, 4, 8, 10 e 12. O "escore de gravidade de xerodermia" foi avaliado em uma escala de 9 pontos, de 0 (pele normal, sem sinais de xerodermia) a 8 (xerodermia grave). A "avaliaçäo geral dos médicos de melhora/piora" foi feita em todas as consultas, exceto na inicial (Tabela 1). Em todas as consultas, com exceçäo da inicial, o pesquisador avaliou se havia alguma diferença entre os dois tipos de abordagem. Se houvesse diferença, o lado tratado era considerado:ligeiramente melhor, moderadamente melhor ou acentuadamente melhor. Também foram documentados os efeitos adversos e feitos "slides" dos locais avaliados nas semanas 0 (antes do tratamento), na semana 8 (final do tratamento) e 12 (final da regressäo)