Focal adhesion kinase confers lenvatinib resistance in hepatocellular carcinoma via the regulation of lysine-deficient kinase 1.

Lenvatinib is a clinically effective multikinase inhibitor approved for first-line therapy of advanced hepatocellular carcinoma (HCC). Although resistance against lenvatinib often emerges and limits its antitumor activity, the underlying molecular mechanisms involved in endogenous and acquired resistance remain elusive. In this study, we identified focal adhesion kinase (FAK) as a critical contributor to lenvatinib resistance in HCC. The elevated expression and phosphorylation of FAK were observed in both acquired and endogenous lenvatinib-resistant (LR) HCC cells. Furthermore, inhibition of FAK reversed lenvatinib resistance in vitro and in vivo. Mechanistically, FAK promoted lenvatinib resistance through regulating lysine-deficient kinase 1 (WNK1). Phosphorylation of WNK1 was significantly increased in LR-HCC cells. Further, WNK1 inhibitor WNK463 resensitized either established or endogenous LR-HCC cells to lenvatinib treatment. In addition, overexpression of WNK1 desensitized parental HCC cells to lenvatinib treatment. Conclusively, our results establish a crucial role and novel mechanism of FAK in lenvatinib resistance and suggest that targeting the FAK/WNK1 axis is a promising therapeutic strategy in HCC patients showing lenvatinib resistance.

Histone 3 lysine 9 acetylation-specific reprogramming regulates esophageal squamous cell carcinoma progression and metastasis.

Dysregulation of histone acetylation is widely implicated in tumorigenesis, yet its specific roles in the progression and metastasis of esophageal squamous cell carcinoma (ESCC) remain unclear. Here, we profiled the genome-wide landscapes of H3K9ac for paired adjacent normal (Nor), primary ESCC (EC) and metastatic lymph node (LNC) esophageal tissues from three ESCC patients. Compared to H3K27ac, we identified a distinct epigenetic reprogramming specific to H3K9ac in EC and LNC samples relative to Nor samples. This H3K9ac-related reprogramming contributed to the transcriptomic aberration of targeting genes, which were functionally associated with tumorigenesis and metastasis. Notably, genes with gained H3K9ac signals in both primary and metastatic lymph node samples (common-gained gene) were significantly enriched in oncogenes. Single-cell RNA-seq analysis further revealed that the corresponding top 15 common-gained genes preferred to be enriched in mesenchymal cells with high metastatic potential. Additionally, in vitro experiment demonstrated that the removal of H3K9ac from the common-gained gene MSI1 significantly downregulated its transcription, resulting in deficiencies in ESCC cell proliferation and migration. Together, our findings revealed the distinct characteristics of H3K9ac in esophageal squamous cell carcinogenesis and metastasis, and highlighted the potential therapeutic avenue for intervening ESCC through epigenetic modulation via H3K9ac.

Evaluation of Papacarie®, Carie-Care™, BRIX3000™ and conventional hand instrumentation for caries removal in primary teeth: a randomized control study.

In the current odontological era, carious lesions are removed while tooth tissue is preserved. Most of these ideals are met by chemomechanical caries removal (CMCR) methods, which are easy and comfortable to use, differentiate and eliminate infected tissues, minimize pressure, vibration and heat, and are cost-effective. This study examines the efficacy of commercially available CMCR agents, namely Papacarie®, Carie-Care™ and BRIX3000™, and a conventional hand instrumentation method for caries removal in deciduous molars in terms of time consumption, ease of application, and pain perception. For this randomized clinical trial, 120 children aged 4 to 9 years were selected and randomly allocated to four groups of 30 patients each. Time consumption, ease of application, and pain perception were evaluated at three intervals: pre-, during- and post-caries removal, using Wong-Baker FACES (WBF) Pain Rating Scale and the Face, Legs, Activity, Cry, Consolability (FLACC) scale. The results showed that among the compared materials and conventional hand instrumentation technique, Carie-Care™ was statistically found to be the least time-consuming with a p-value of 0.019, have the least pain perception with a p-value of 0.02, and was clinically the best with respect to manipulation and handling. While all three CMCR agents aid in the removal of carious tissue, Carie-Care™ was the most effective based on time consumption, pain perception and simplicity of administration.

Acid Neutralization by Composite Lysine Nanoparticles for Spinal Cord Injury Recovery through Mitigating Mitochondrial Dysfunction.

After spinal cord injury (SCI), significant alterations in the tissue microenvironment lead to mitochondrial dysfunction, inducing apoptosis and inhibiting the remodeling of neural circuits, thereby impeding recovery. Although previous studies have demonstrated a marked decrease in pH at the injury site, creating an acidic microenvironment, the impact of improving this acidic microenvironment on SCI recovery has not been investigated. This study prepared a lysine@hollow mesoporous silica nanoparticle/gelatin methacrylate (GelMA) (L@H/G) composite hydrogel. The L@H/G composite hydrogel was demonstrated to release lysine and efficiently improve the acidic microenvironment slowly. Significantly, the composite hydrogel reduced cell apoptosis, promoted nerve regeneration, inhibited glial scar formation, and ultimately enhanced motor function recovery in mice with SCI. Mechanistically, the L@H/G hydrogel improved the mitochondrial tricarboxylic acid (TCA) cycle and fatty acid metabolism, restoring energy supply and facilitating mitochondrial function recovery. To the best of our knowledge, this is the first report confirming that improving the acidic microenvironment could promote SCI repair, providing a potential therapeutic strategy for SCI.

Efficacy of Ibuprofen Lysine on First-Trimester AbortionRelated Pain and Hemorrhage: A Randomized TripleBlinded Clinical Trial.

BACKGROUND: Some recent trials have reported high efficacy for nonsteroidal anti-inflammatory drugs (NSAIDs) in relieving medical abortion-related pain. The aim of this study was to determine the beneficial effect of oral NSAIDs (ibuprofen lysine) in reduction of pain and hemorrhage in first-trimester medical abortion. METHODS: This randomized triple-blinded clinical trial was performed on 98 pregnant women who were candidate for medical abortion within the first-trimester period (gestational age<12 weeks). The participants were randomly assigned to receive ibuprofen lysine (684 mg orally every 4 hours) or placebo. All patients were initially treated with misoprostol (800 µg every 3 hours). Pain intensity and rate of hemorrhage were assessed every hour up to 15 hours after receiving the first dose of misoprostol by visual analogue scaling (VAS) and pictorial blood loss assessment chart (PBAC), respectively. RESULTS: Assessing the mean pain score within 15 hours of receiving misoprostol showed significantly lower pain intensity within the first 10 hours of assessment in the group receiving NSAID in comparison with the control group (P<0.001). The bleeding rate was also significantly lower in the NSAID group at the fifth (P=0.013) and ninth (P=0.040) hour of receiving misoprostol compared to the control group. We found no difference in abortion-related complication rate between the NSAID and placebo groups (8.3% versus 8.0%, P=0.952). CONCLUSION: The use of NSAIDs (ibuprofen lysine) is a good pharmacological analgesic option for relieving medical abortionrelated pain and hemorrhage.

Red propolis and L-lysine on angiogenesis and tumor growth in a new model of hamster cheek pouch inoculated with Walker 256 tumor cells / Própolis vermelha e L-lisina na angiogênese e no crescimento tumoral em novo modelo de bolsa jugal de hamster inoculada com células de tumor de Walker 256

ABSTRACT Objective: To evaluate the effect of red propolis and L-lysine on angiogenesis and tumor growth in a new model of hamster cheek pouch inoculated with Walker 256 tumor cells. Methods: The study consisted of two experiments with four groups each (total: 57 hamsters). In the experiment 1, the animals were inoculated with Walker tumor cells, followed by administration of test substances (red propolis 200mg/5mL/kg or L-lysine 150mg/kg) or control substances (gum arabic 5mL/kg or water 5mL/kg) for 10 days. The animals in the experiment 2 received red propolis, L-lysine, gum arabic or water at the same doses, for 33 days prior to inoculation of Walker tumor cells, followed by 10 days of treatment with the same substances. Based on single-plane images, angiogenesis was quantified (mean vascular area), in percentage, and tumor area (mm2) and perimeter (mm). Results: In the experiment 1, compared to animals receiving water, the mean vascular area expressed in percentage was significantly smaller in animal treated with propolis (p<0.05) and L-lysine (p<0.001). Conclusion: Both red propolis and L-lysine inhibited tumor angiogenesis in the new hamster cheek pouch model when administered after tumor inoculation.

RESUMO Objetivo: Avaliar o efeito da própolis vermelha e da L-lisina na angiogênese e no crescimento tumoral em novo modelo de bolsa jugal de hamster inoculada com células de tumor de Walker 256. Métodos: O estudo consistiu em dois experimentos com quatro grupos cada (total: 57 hamsters). No experimento 1, os animais foram inoculados com células de tumor de Walker, tendo em seguida administradas as substâncias teste (própolis vermelha 200mg/5mL/kg ou L-lisina 150mg/kg) ou controle (goma arábica 5mL/kg ou água 5mL/kg) por 10 dias. Os animais do experimento 2 receberam própolis vermelha, L-lisina, goma arábica ou água nas mesmas doses, por 33 dias antes do inóculo das células de tumor de Walker, seguido por 10 dias de tratamento com as mesmas substâncias. Baseado em imagens em plano único, foram quantificados a angiogênese (área vascular média), em termos percentuais, e a área (mm2) e o perímetro (mm) do tumor. Resultados: Comparada aos animais que receberam água, a área vascular média, expressa em percentagem, foi significativamente menor nos animais tratados com própolis (p<0,05) e com L-lisina (p<0,001). Conclusão: Tanto a própolis vermelha quanto a L-lisina inibiram a angiogênese no novo modelo de bolsa jugal de hamsters, quando administradas após a inoculação do tumor.

Angiogenesis inhibition by green propolis and the angiogenic effect of L-lysine on bladder cancer in rats / Inibição da angiogênese pela própolis verde e efeito angiogênico da L-lisina no câncer de bexiga em ratos

PURPOSE: To determine the effects of water-soluble derivative of green propolis in bladder cancer angiogenesis in rats given N-butyl-(-4-hydroxybutyl) nitrosamine (BBN). METHODS: Nine groups were established, where six of them (Groups 1 to 6), the animals received 0.05% BBN in their drinking water for 14 weeks. From the 32nd to the 40th week, Groups 1, 2, 3 and 4 were treated respectively with water, L-lysine (300 mg/kg/day), celecoxib (30 mg/kg/day) and propolis (300 mg/kg/day). Groups 5 and 6 were given propolis and L-lysine from the 1st to the 40th week (150 mg/kg/day). Microvascular density was determined by histological sections stained for the marker CD-31 and analyzed with specific software. RESULTS: The microvascular density in bladder carcinomas was lower (p<0.01) in rats receiving propolis than in controls given carcinogen only. On the other hand, the microvascular density of tumors in rats receiving carcinogen and L-lysine for 40 weeks from the beginning of carcinogen treatment was significantly higher (p<0.01) than in the corresponding controls. CONCLUSION: Water-soluble derivative of propolis inhibits angiogenesis in BBN-induced rat bladder cancer, while L-lysine treatment stimulates angiogenesis if initiated concurrently with BBN.

OBJETIVO: Determinar os efeitos da própolis verde solúvel em água na angiogênese de câncer de bexiga em ratos que receberam n-butil-(-4-hidroxibutil) nitrosamina (BBN). METODOS: Nove grupos foram estabelecidos, onde em seis destes (grupos de 1 a 6) os animais receberam BBN a 0,05% em água de beber por 14 semanas. Na 32ª semana das 40 semanas, os grupos 1, 2, 3 e 4 foram tratados respectivamente com água, L lisina (300 mg/kg/dia), celecoxibe (30 mg/kg/dia) e própolis (300 mg/kg/dia). Os grupos 5 e 6 receberam própolis e L lisina da 1ª a 40ª semana (150 mg/ kg/dia). A densidade microvascular foi determinada por cortes histológicos corados pelo CD-31 e analisados por programa de computador específico. RESULTADOS: A densidade microvascular em carcinomas de bexiga foi menor com p<0,01 nos ratos que receberam própolis do que nos carcinomas do grupo controle que recebeu apenas carcinógeno. Por outro lado, a densidade microvascular de tumores de ratos que receberam carcinógeno e L-Lisina por 40 semanas desde o início do carcinógeno foi significantemente maior com p<0,01 que a densidade microvascular dos tumores de seu respectivo grupo controle. CONCLUSÃO: A própolis verde solúvel em água inibiu a angiogênese em câncer de bexiga induzido pelo BBN, enquanto a L- lisina estimulou a angiogênese quando iniciada juntamente com o BBN.

Remoção químico-mecânica da cárie dental com o uso de CarisolvTM: [revisão] / Chemomechanical caries removal using CarisolvTM: [review]

Introdução: a Odontologia vem aprimorando as técnicas de remoção do tecido cariado, visando facilitar a rotina clínica. Um desses avanços foi a introdução de mecanismos para a remoção químico-mecânica da cárie dental. Tradicionalmente, a remoção do tecido cariado tem sido realizada por meio de métodos mecânicos, como a utilização de instrumentos cortantes rotatórios e manuais que embora tenham se mostrado efetivos, apresentam desvantagens como a dor e eventual remoção de tecido sadio. Objetivo: estudar as vantagens e as desvantagens da técnica operatória de um método químico-mecânico quando se utiliza o produto CarisolvTM, bem como conhecer a sua composição e o seu mecanismo de ação. Conclusão: a remoção de tecido cariado com o CarisolvTM promove tanto a eliminação de S.mutans quanto a de Lactobacillus, entretanto é um processo controverso no que tange a sua eficácia e a ausência de dor visto que, eventualmente, é necessário o uso de instrumentos cortantes rotatórios para complementar a remoção de tecido cariado, possui um custo elevado e consome um maior tempo clínico quando comparado à remoção mecânica da cárie dental.

Introduction: dentistry is improving techniques for caries removal, intending to facilitate the clinical routine. Such advancement was the introduction of chemical-mechanical caries removal mechanisms. Traditionally, the carious lesion removal has been held by mechanical methods such as the use of rotary and manual cutting tools, which have been shown effective nevertheless, have disadvantages as pain and eventual removal of healthy tissue. Aim: study the advantages and disadvantages of a chemical-mechanical surgical technique when using the product CarisolvTM and know its composition and its acting mechanism. Conclusion: caries removal with CarisolvTM promotes both S.mutans as Lactobacillus elimination. In the meantime is a controversial process with regard to its effectiveness and pain absence because, eventually, it is necessary to use rotary cutting tools to complement the caries removal, has a high cost and consumes a larger clinical time when compared to dental caries mechanical removal.

Comparasion of two minimally invasive methods on the longevity of glass ionomer cement restorations: short-term results of a pilot study

The purpose of this study was to evaluate the clinical performance of glass ionomer cement (GIC) restorations comparing two minimally invasive methods in permanent teeth after 12 months. Fifty pregnant women (second trimester of pregnancy), mean age 22 ± 5.30 years, were treated by two previously trained operators. The treatment approaches tested were: chemomechanical method (CarisolvTM; MediTeam) and atraumatic restorative treatment (ART). A split-mouth study design was used in which the two treatments were randomly placed in 50 matched pairs of permanent teeth. The chemomechanical method (CM) was the test group and the ART was the control group. The treatments were performed in Public Health Centers. The tested restorative material was a high-strength GIC (Ketac Molar; 3M/ESPE). The restorations were placed according to the ART guidelines. Two calibrated independent examiners evaluated the restorations in accordance with ART criteria. The inter-examiner kappa was 0.97. Data were analyzed using 95 percent confidence interval on the binomial distribution and Fisher's exact test at 5 percent significance level. In a 12-month follow-up, 86 percent of the restorations were evaluated. In the test group (CM), 100 percent (CI=93.3-100 percent) of the restorations were considered successful. In the control group (ART) 97.6 percent (CI=87.4-99.9 percent) of the restorations were considered successful and 2.4 percent unsuccessful (marginal defect >0.5 mm). There was no statistically significant difference between the 12-mounth success rate for both groups (Fisher's exact test: P=0.49) and between the two operators (Fisher's exact test: P=1.00). Both minimally invasive methods, chemomechanical method and ART, showed a similar clinical performance after 12 months of follow up.

Lysine clonixinate versus dipyrone (metamizole) for the acute treatment of severe migraine attacks: a single-blind, randomized study / Clonixinato de lisina versus dipirona (metamizol) para o tratamento agudo de uma crise intensa de enxaqueca: estudo monocego e randomizado

BACKGROUND AND OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAID) are effective to treat migraine attacks. Lysine clonixinate (LC) and dipyrone (metamizol) have been proven effective to treat acute migraine. The aim of this study was to evaluate the efficacy and tolerability of the intravenous formulations of LC and dipyrone in the treatment of severe migraine attacks. METHOD: Thirty patients (28 women, 2 men), aged 18 to 48 years with migraine according the International Headache Society (IHS) (2004) were studied. The patients were randomized into 2 groups when presenting to an emergency department with a severe migraine attack. The study was single-blind. Headache intensity, nausea, photophobia and side effects were evaluated at 0, 30, 60 and 90 minutes after the drug administration. Rectal indomethacin as rescue medication (RM) was available after 2 hours and its use compared between groups. RESULTS: All patients completed the study. At 30 minutes, 0 percent of the dipyrone group 13 percent of the LC group were pain free (p=0.46). At 60 and 90 minutes, 2 (13 percent) and 5 (33 percent) patients from the dipyrone group and 11 (73 percent) and 13 (86.7 percent) patients from the LC group were pain free (p<0.001). At 60 minutes, significantly more patients from the LC group were nausea-free (p<0.001). Regarding photophobia, there were no differences between groups at 60 minutes (p=0.11). The use of RM at 2 hours did not differ among groups (p=0.50). Pain in the site of the injection was reported by more patients of the LC group compared to the dipyrone group (p<0.0001). CONCLUSION: LC is significantly superior to dipyrone in treating severe migraine attacks. LC promotes significantly more burning at the site of the injection.

CONTEXTO E OBJETIVO: Antiinflamatórios não esteroidais (AINE) são eficazes no tratamento de crises de enxaqueca. O objetivo deste estudo foi comparar a eficácia e a tolerabilidade das apresentações injetáveis do clonixinato de lisina (CL) e da dipirona no tratamento de crises intensas de enxaqueca. MÉTODO: Trinta pacientes (28 mulheres, 2 homens), com idades entre 18 e 48 anos e enxaqueca de acordo com a Classificação Internacional de Cefaléias (2004) foram estudados. Os pacientes foram randomizados em 2 grupos ao se apresentarem em uma unidade de emergência, com uma crise intensa de enxaqueca. O desenho do estudo foi monocego. A intensidade da cefaléia, a presença de náusea e fotofobia e os efeitos colaterais foram avaliados e comparados na administração das drogas e após 30, 60 e 90 minutos. Indometacina retal foi disponibilizada como droga de resgate (DR) e seu uso comparado entre os grupos. RESULTADOS: Todos os pacientes completaram o estudo. Após 30 minutos, 0 por cento do grupo da dipirona e 13 por cento do CL encontravam-se sem cefaléia (p=0,46). Após 60 e 90 minutos, 2 (13 por cento) e 5 (33 por cento) do grupo da dipirona e 11 (73 por cento) e 13 (86,7 por cento) do grupo do CL encontravam-se sem cefaléia (p<0,001). Após 60 minutos, o CL foi mais eficaz que a dipirona em eliminar a náusea (p<0,001), mas não houve diferença quanto à melhora da fotofobia entre os grupos (p=0,11). Não houve diferenças entre os grupos que utilizaram DR (p=0,50). Dor no local da injeção foi apresentada por mais pacientes que usaram CL comparados aos da dipirona (p<0,001). CONCLUSÃO: O CL é significativamente superior a dipirona no tratamento de uma crise intensa de enxaqueca, mas resulta em mais queimação no local da injeção.

In vitro evaluation of marginal leakage in bonded restorations, with mechanical or chemical-mechanical (Carisolv) removal of carious tissue

This study carried out an in vitro evaluation and comparison of the occurrence of marginal leakage in bonded restorations using mechanical or chemical-mechanical (Carisolv) removal of carious tissue. For that purpose, 40 extracted decayed human molars were divided into 4 groups: GI (burs + Prime & Bond NT + TPH), GII (Carisolv + Prime & Bond NT + TPH), GIII (burs + SBMP + Z100) and GIV (Carisolv + SBMP + Z100). After accomplishment of the restorations and thermal cycling, the teeth were exposed to dye, sectioned and qualitatively evaluated. The results demonstrated that the system of removal of carious tissue did not influence the results of microleakage at any of the cavity margins. At dentinal margins, use of the Prime & Bond NT + TPH restorative system allowed the occurrence of less microleakage than the SBMP + Z100 system.

Este estudo avaliou e comparou in vitro a ocorrência da infiltração marginal em restaurações adesivas, com a utilização de remoção mecânica e químico-mecânica do tecido cariado. Para a proposição, 40 dentes molares humanos extraídos cariados foram divididos em quatro grupos: GI (brocas + Prime & Bond NT + TPH), GII (Carisolv + Prime & Bond NT + TPH), GIII (brocas + SBMP + Z100) e GIV (Carisolv + SBMP + Z100). Após a execução das restaurações e termociclagem, os dentes foram expostos a corante, seccionados e avaliados qualitativamente. Os resultados demonstraram que o sistema de remoção de tecido cariado não influenciou a ocorrência de microinfiltração em quaisquer margens cavitárias. Nas margens dentinárias, a utilização do sistema restaurador Prime & Bond NT + TPH demonstrou menor ocorrência de microinfiltração do que o sistema SBMP + Z100.

Efficacy of Carisolv™ as an adjunctive therapy to scaling and root planing on subgingival calculus removal

The purpose of this study was to evaluate the effectiveness of subgingival application of Carisolv™ gel as an adjunctive therapy to scaling and root planing (SRP) on calculus removal compared to conventional instrumentation. Forty-five teeth requiring extraction due to severe periodontal disease were randomized to the following treatments: 1) SRP alone; 2) placebo gel + SRP; 3) Carisolv™ gel + SRP. Either test or placebo gel was applied subgingivally for 1 min and then the root were instrumented until a smooth and calculus-free surface was achieved. Instrumentation time and the number of strokes required were recorded. After extraction, the efficacy of root surface instrumentation was measured by percentage of remaining calculus. There was no statistically significant difference (p>0.05) between the treatment groups regarding either time required for instrumentation or the percentage of residual calculus. The subgingival application of Carisolv™ gel prior to SRP did not provide any additional benefit to root instrumentation compared to scaling and root planing alone.

O objetivo deste estudo foi avaliar a efetividade da aplicação subgengival do gel Carisolv™ em associação aos procedimentos de raspagem e alisamento radicular (RAR) na remoção do cálculo dental aderido à superfície radicular, quando comparado à terapia periodontal mecânica convencional. Foram utilizados 45 dentes indicados para a exodontia devido à doença periodontal avançada, os quais foram divididos em três grupos de tratamento: 1) RAR apenas; 2) placebo + RAR; 3) Carisolv™ + RAR. O tempo despendido e o número de movimentos realizados para a instrumentação das superfícies radiculares foram avaliados durante o tratamento. Em seguida, os dentes foram extraídos e avaliados quanto ao percentual de cálculo residual, por meio de um sistema computadorizado de análise de imagens. Não houve diferença estatisticamente significante (p>0,05) entre os grupos com relação ao tempo requerido para os diferentes tratamentos, assim como quanto ao percentual de cálculo residual. Os resultados indicaram que a aplicação do Carisolv™ não promoveu benefícios adicionais àqueles obtidos com a terapia mecânica convencional na remoção do cálculo subgengival.

Evaluation of the methodologies used in clinical trials and effectiveness of chemo-mechanical caries removal with CarisolvTM

This investigation aims to discuss the methodologies applied in clinical trials published about CarisolvTM, in order to assess the best scientific evidence concerning chemo-mechanical caries removal. Papers concerning the use of CarisolvTM were sought using a search strategy. The titles and abstracts of all the reports identified through the search were analyzed by a single reviewer. The inclusion criterion involved: clinical trials having CarisolvTM in one of the study groups. Then, those that fulfilled the inclusion criterion underwent methodology assessment and data extraction. Only 12 papers met the inclusion criterion. It was observed that none of these studies complied with all the evaluated research methodological principles required in order to have power of evidence generation. CarisolvTM proved to be effective in caries removal. Appointment mean time was greater, but the perceived time was shorter than that using conventional techniques due to patients' perception of more comfort and a reduction of anesthesia needs. There were no adverse effect in long-term assessments. In studies with microbiological evaluation of the remaining dentine, it was observed that both the conventional and chemo-mechanical methods produced statistically significant reduction on counts of viable microorganisms.

Esta investigação objetiva discutir as metodologias aplicadas em ensaios clínicos publicados sobre Carisolv®, para verificar a melhor evidência científica concernente à remoção químico-mecânica de tecido cariado. Artigos referentes ao uso de Carisolv® foram procurados utilizando-se uma estratégia de busca. Os títulos e resumos de todos os estudos identificados pela procura foram analisados por um único revisor. O critério de inclusão envolveu: ensaios clínicos contendo o sistema Carisolv® em um dos grupos de estudo. Os estudos que preencheram o critério de inclusão foram submetidos à avaliação de metodologia e extração de dados. Somente 12 artigos preencheram o critério para inclusão. Foi verificado que nenhum desses estudos obedeceu a todos os princípios metodológicos considerados necessários para que uma pesquisa tenha poder de geração de evidências. O Carisolv® demonstrou ser eficaz na remoção de tecido cariado. O tempo de consulta foi maior, mas o tempo percebido foi inferior em comparação ao tempo das técnicas convencionais devido à percepção dos pacientes de mais conforto e de redução da necessidade de anestesia. Não houve efeito adverso em avaliações a longo prazo. Em estudos com avaliação microbiológica da dentina remanescente foi verificado que ambos os métodos convencional e químico-mecânico produziram redução significativa na contagem de microrganismos viáveis.

Analgesic efficacy of Lysine Clonixinate, paracetamol and dipyrone in lowerthird molar extraction. A randomized controlled trial

Objective: The purpose of this study is to compare the analgesic effect of lysine clonixinate, paracetamol anddipyrone after lower third molar extraction.Material and Methods: The sample consisted of 90 individuals, with clinical indication for inferior third molarsextraction. The mean age of the sample was 22.3 years (DP±2.5). The individuals received the medication in unidentifiedbottles along with the intake instructions. The postoperative pain parameters were measured accordingto Visual Analogical Scale (VAS) and the data was evaluated using the Kruskal-Wallis Test and Friedman Test,with the latter used to test different time intervals for each one of the drugs.Results: The final sample consisted of 64 individuals, including 23 males (45.9%) and 41 females (64.1%) Themean age of the entire sample was 22.3 years (±2.5). The average length of the procedures was 33.9 minutes (±9.8).The distribution of mean values for this variable showed little variance for the different drugs (p=0.07).Conclusion: Lysine Clonixinate did not show any substantial impact on the postoperative pain control when comparedto other drugs (AU)

No disponible

Efeito da lisina na incidência e duração das lesões de herpes labial recorrente / The effect of lysine in the incidence and period of healing of recurrent herpes labialis

Objetivos: O objetivo do presente estudo foi testar o efeito da lisina na incidência e duração dos ciclos das lesões recorrentes de herpes labial. Métodos: Foram incluídos no estudo 12 indivíduos, sendo cinco do gênero masculino e sete femininos, com idade entre 30 e 48 anos, acometidos de lesões de herpes labial recorrentes com manifestações que variavam de uma ao mês até uma a cada três meses. O tratamento com lisina foi instituído na fase de crosta de uma lesão utilizando uma cápsula de 5OOmg ao dia durante 30 dias. Resultados: Os resultados mostraram uma redução média de 49% no ciclo das lesões e de 63% na incidência das lesões em um ano. Conclusão: Dentro dos limites do presente estudo, pode-se concluir que a lisina apresentou resultados positivos na redução da incidência e ciclo das lesões recorrentes. Entretanto, ensaios clínicos controlados randomizados em amostras maiores são necessários para que a eficiência desta droga seja comprovada.

Lysine clonixinate in the treatment of primary dysmenorrhea

The efficacy tolerance of Lysine Clonixinate (LC), a NSAID with prostaglandin synthesis inhibiting mechanism was studied in 24 patients with primary dysmenorrhea according to a double-blind randomized crossover Placebo (P) controlled design with patients serving as their own controls. Treatment consisted in administering 1 tablet of LC or P q6h as from onset of menstrual pain during 5 days and 6 menstrual cycles. Patients were controlled monthly as from the 5th day of the cycle rating changes in pain intensity according to a 4-point scale, presence of pain during pre-, post-and menstrual periods: possible intracycle changes, amount of bleeding, tolerance and related total and general signs and symptons. Intensity of baseline menstrual pain amounted to 2.9. Menstrual, intramenstrual and postmenstrual pains were observed in 19 out of 24,24/24 and only 2 out of the patients, respectively. Concomitant symptons consisted in headache (12), mastalgia (14) and disconfort (12). Results were obtained by averaging the data from the 3 tratment periods with each drug. Menstrual pain was reduced from 2.9 + 0.7 to 1.9 + 0.7 with P administration and to 0.66 + 0.4 with the administration of LC, a highly significant difference between tratments (p<0.0001). Premenstrual pain was reduced nonsignificantly from 0.79 per cent to 0.58 per cent with P administration and significantly to 0.29 per cent with administration of LC (p<0.001). Intramenstrual pain affection all patients at baseline was reduced significantly by 8 per cent with P and also significantly by 50 per cent with LC p<0.001). No differences were encontered in encomitant symptoms during P treatment periods while the incidence was significantly reduced with LC (p<0.0001). No changes in cycle duration or amount of bleeding were observed between treatments. No adverse events were reported.

Tratamiento del cólico renal / Treatment of the renal colic

Se compara la respuesta obtenida con el uso de dipirona, atropina y papaverina(DAP) y de acetil salicilato de lisina(ASL), en el tratamiento del dolor del cólico renal. Se analisan 162 pacientes con cuadro clínico de cólico renal, repartiéndolos aleatoriamente en dos grupos y evaluando su respuesta al dolor en un control de doble ciego. Un grupo estuvo constituído por 80 pacientes a los que se les administró ASL endovenoso y el otro por 22 enfermos que se trataron con una dosis endovenosa de DAP. Se comenta brevemente la fisiopatología del cólico renal, destacando los factores conducentes a la hipertensión retrógrada del sistema pieloureteral, así como los mecanismos terapéuticos orientados a reducirla. La respuesta al tratamiento se evaluó a los 15 minutos de acuerdo a una escala previamente establecida, observándose una desaparición completa del dolor en el 55 por ciento de los pacientes tratados con ASL y sólo en el 19.5 por ciento de los tratados con DAP (p=0..25)

Effecto del clonixinato de lisina y la indometacina sobre la actividad de la lipooxigenasa y la ciclooxigenasa de colon aislado de pacientes con neoplasias / Effect of lysine clonixinate and indomethacin on the lipooxygenase and cycloogygenase activity of clon isolated from cancer patients

Las ulceraciones de la mucosa gástrica y colónica producida por los antiinflamatorios no esteroides (AINES) son producidas por la reducción de la síntesis de prostaglandinas (PGs) por inhibición de la ciclooxigenasa. Por otro lado se ha demosntrado que los productos de la 5-lipoxigenasa (5-LO) son agentes ulcerogénicos. En algunos casos el uso de AINES se acompaña de una mayor producción de productos de la 5-LO debido a un exceso de sustrato (ácido araquidónico) al estar bloqueada la ciclooxigenasa. Cuando ocurre esto último aumentan los efectos lesivos de los AINES ya que no sólo disminuyen las PGS citoprotectoras, sino que también aumentan los productos de la 5-LO. El objeto de este trabajo, fue estudiar en segmentos de colon aislado de pacientes con neoplasias el efecto del Clonixinato de lisina (CL) y de la indometacina (INDO) sobre la síntesis de PGs e hidroxiácidos (HETEs). Las concentraciones de CL (4 y 6 mug/ml) y de indo (0,035 y 0,035 y 0,35 mug/ml utilizadas, se corresponden con los valores plasmáticos alcanzados con dosis terapéuticos orales de ambas drogas. Se observó que el CL con ninguna de las dosis utilizadas modificó la producción basal de PGE(2). Por el contrario la INDO inhibió significativamente la síntese de PGE(2) con ambas dosis. Llamó la atención que el CL tanto a 4 mug/ml como 6 mug/ml produjo una profunda disminución en la producción de 5-HETE, efecto sólo observado con la concentración más alta de INDO. Este resultado indicaría una probable acción inhibitoria sobre la 5-LO, primeira enzima del camino metabólico del ácido araquidónico hacia formación de HETEs y Lts. Concluimos que el CL en dosis terapéuticas tiene un mecanismo de acción diferente al de los AINES clásicos. Los datos obtenidos en este estudo explicarían la baja incidencia de efectos gastrointestinales lesivos observados con CL.

Eficácia e tolerabilidade do acetilsalicilato de lisina em algumas formas de reumatismo extra-articular / Efficacy and tolerance of lysine-acetylsalicylate on soft tissue rheumatism

Vinte e nove pacientes com diagnóstico de lombalgia (14), cervicalgia (nove) e periartrite de ombro (seis) de, no máximo, cinco dias de duraçäo, foram submetidos a tratamento com acetilsalicilato de lisina (ASL) na dose de 2,0 g quatro vezes ao dia. Com o objetivo de se avaliar a eficácia e a tolerabilidade da droga, foram analisados os parâmetros objetivos através da amplitude de movimento e parâmetros subjetivos. Os resultados mostraram uma melhora estatisticamente significante da amplitude de movimento, e 89,3% dos pacientes, após 15 dias de tratamento, consideraram o resultado como excelente ou bom. O tratamento foi interrompido em apenas um paciente devido a efeitos gastrointestinais indesejáveis, entretanto em 25 pacientes a tolerabilidade foi considerada excelente e boa, e regular em três. Conclui-se que por ser o ASL eficaz e de boa tolerabilidade no tratamento dos reumatismos de partes moles, possa vir a ser usado prioritariamente, antes de medidas mais dispendiosas e de maior risco para os pacientes