Impact of Cuminaldehyde and Indomethacin Co-Administration on Inflammatory Responses in MIA-Induced Osteoarthritis in Rats.

Osteoarthritis (OA) remains a chronic incurable condition, presenting substantial challenges in treatment. This study explores a novel strategy by investigating the concurrent use of cuminaldehyde, a natural compound, with indomethacin in animal models of MIA-induced OA. Our results demonstrate that the co-administration of cuminaldehyde and indomethacin does indeed produce a superior effect when compared to these compounds individually, significantly enhancing therapeutic outcomes. This effect is evidenced by a marked reduction in pro-inflammatory cytokines IL-6 and IFN-γ, alongside a significant increase in the anti-inflammatory cytokine IL-10, compared to treatments with each compound alone. Radiographic analyses further confirm the preservation of joint integrity and a reduction in osteoarthritic damage, highlighting the association's efficacy in cartilage-reducing damage. These findings suggests that the association of cuminaldehyde and indomethacin not only slows OA progression but also offers enhanced cartilage-reducing damage and fosters the production of protective cytokines. This study underscores the potential benefits of integrating natural products with pharmaceuticals in OA management and stresses the importance of further research to fully understand the mechanisms underlying the observed potentiated effects.

Cuminaldehyde Effects in a MIA-Induced Experimental Model Osteoarthritis in Rat Knees.

Osteoarthritis (OA) is a chronic degenerative disease that has a significant global impact. It is associated with aging and characterized by widespread joint destruction. Cuminaldehyde is a biologically active component of essential oils that has shown promise in the treatment of nociceptive and inflammatory diseases. This study investigated the effects of cuminaldehyde on an experimental model of osteoarthritis induced in rat knees. Cuminaldehyde was found to be as effective as indomethacin in reducing pain in all evaluated tests, including forced walking, functional disability of weight distribution on the legs, and spontaneous pain in animals with osteoarthritis. The knees of animals treated with cuminaldehyde had significantly higher radiographic and histopathological scores than those of animals that did not receive the treatment. Cuminaldehyde also modulated the production of pro-inflammatory cytokines. In vitro assays showed that cuminaldehyde preferentially inhibits COX-2 enzyme activity. In silico studies demonstrated that cuminaldehyde has satisfactory energy affinity parameters with opioid receptors and COX-2. These findings suggest that cuminaldehyde's anti-inflammatory activity is multifactorial, acting through multiple pathways. Its nociceptive activity occurs via central and peripheral mechanisms. Cuminaldehyde modulates the immune response of the inflammatory process and may be considered a leading compound for the development of new anti-inflammatory and analgesic drugs.

Valores normais da manometria de alta resolução de esôfago: estudo multicêntrico brasileiro / Normal values of esophageal high-resolution manometry: a brazilian multicenter study

ABSTRACT BACKGROUND: The high-resolution manometry has been a significant advance in esophageal diagnostics. There are different types of catheter and systems devices to capture esophageal pressures that generate variable data related to Chicago Classification (CC) and consequently influence normal values results. There are not normative data for the 24-channel water-perfused high-resolution manometry system most used in Brazil with healthy volunteers in supine posture. OBJECTIVE: To determine manometric esophageal normative values for a 24-channel water-perfused high-resolution manometry catheter in supine posture using healthy volunteers according to CC 3.0 parameters. METHODS: A total of 92 volunteers with no gastrointestinal symptoms or medications affecting GI motility underwent esophageal high-resolution manometry by standard protocol. Age, gender and manometry parameters analyzed using Alacer software were collected. The median, range, and 5th and 95th percentiles (where applicable) were obtained for all high-resolution manometry metrics. Normal value percentiles were defined as 95th integrated relaxation pressure, 5th-100th distal contractile integral, and 5th distal latency. RESULTS: The mean age was 40.5±13.2 years. Our normative metrics were integrated relaxation pressure <16 mmHg and distal contractile integral (708-4111 mmHg.cm.s) distal latency was <6 s and peristaltic break size (>4 cm). For EGJ-CI the range 5th-95th was 21.7-86.9 mmHg.cm.s. CONCLUSION: This is the first report of normative data for the 24-channel water-perfused system in supine posture. It revealed higher integrated relaxation pressure and distal latency duration which suggest the need to change CC 3.0 cutoffs for this system. It is observed that there is a tendency that DCI >7000 mmHg.cm.s may represent the lower limit of hypercontractility, and when <700 mmHg.cm.s (<5% percentile) interpreted as ineffective esophageal motility or failcontraction. Also compared to Chicago 3.0, higher integrated relaxation pressure and duration of distal latency were found. We emphasize that these data must be confirmed by future studies.

RESUMO CONTEXTO: A manometria de alta resolução tem sido um avanço significativo nos diagnósticos esofágicos. Existem diferentes tipos de cateteres e sistemas dispositivos para capturar pressões esofágicas que geram dados variáveis relacionados à Classificação de Chicago (CC) e, consequentemente, podem influenciar os resultados de valores da normalidade. Não há dados normativos com voluntários saudáveis na postura supina, para o sistema manométrico sob perfusão em água de 24 canais, o mais utilizado no Brasil. OBJETIVO: Determinar os valores normativos manométricos do esôfago para um cateter sob perfusão de alta resolução de 24 canais na postura supina utilizando-se voluntários saudáveis assintomáticos de acordo com os parâmetros CC. MÉTODOS: Um total de 92 voluntários sem sintomas gastrointestinais ou medicamentos que afetassem a motilidade gastrointestinal foram submetidos à manometria de alta resolução do esôfago por protocolo padrão (Sistema Alacer Multiplex). Foram coletados parâmetros de idade, sexo e os da manometria analisados pelo software Alacer versão 6.2. A mediana, os limites, e 5% e 95% percentis (quando aplicável) foram obtidos para todas as métricas de alta resolução. Os valores normais foram definidos como percentis de 95% da integral da pressão de relaxamento (IRP), 5%-100% da integral contrátil distal (DCI), e 5% latência distal. RESULTADOS: A média de idade foi de 40,5±13,2 anos. As métricas normativas foram definidas como IRP <16 mmHg) e DCI (708-4111 mmHg.cm.s). Para a latência distal foi de 5,8-9,9 s (faixa: 5,3-10,7s). O comprimento total de quebra na contração esofágica foi de 4,0 cm (faixa: 0,1-6,8 cm). Para a EGJ-CI a faixa 5%-95% percentis foi de 21,7-86,9 mmHg.cm.s. CONCLUSÃO: Este é o primeiro relatório de dados normativos para o sistema de 24 canais perfundido por água na postura supina. A partir dos dados encontrados observa-se a possibilidade de alterar os cortes CC 3.0 para este sistema. Observa-se que há uma tendência que DCI >7000 mmHg.cm.s possa representar o limite inferior da hipercontratilidade e quando <700 mmHg.cm.s (<5% percentil) interpretada como motilidade esofágica ineficaz ou contração falha. Também em comparação com Chicago 3.0, foi encontrada maior pressão de relaxamento integrado e duração da latência distal. Ressaltamos que esses dados devem ser confirmados por estudos futuros.

NORMAL VALUES OF ESOPHAGEAL HIGH-RESOLUTION MANOMETRY: A BRAZILIAN MULTICENTER STUDY.

BACKGROUND: The high-resolution manometry has been a significant advance in esophageal diagnostics. There are different types of catheter and systems devices to capture esophageal pressures that generate variable data related to Chicago Classification (CC) and consequently influence normal values results. There are not normative data for the 24-channel water-perfused high-resolution manometry system most used in Brazil with healthy volunteers in supine posture. OBJECTIVE: To determine manometric esophageal normative values for a 24-channel water-perfused high-resolution manometry catheter in supine posture using healthy volunteers according to CC 3.0 parameters. METHODS: A total of 92 volunteers with no gastrointestinal symptoms or medications affecting GI motility underwent esophageal high-resolution manometry by standard protocol. Age, gender and manometry parameters analyzed using Alacer software were collected. The median, range, and 5th and 95th percentiles (where applicable) were obtained for all high-resolution manometry metrics. Normal value percentiles were defined as 95th integrated relaxation pressure, 5th-100th distal contractile integral, and 5th distal latency. RESULTS: The mean age was 40.5±13.2 years. Our normative metrics were integrated relaxation pressure <16 mmHg and distal contractile integral (708-4111 mmHg.cm.s) distal latency was <6 s and peristaltic break size (>4 cm). For EGJ-CI the range 5th-95th was 21.7-86.9 mmHg.cm.s. CONCLUSION: This is the first report of normative data for the 24-channel water-perfused system in supine posture. It revealed higher integrated relaxation pressure and distal latency duration which suggest the need to change CC 3.0 cutoffs for this system. It is observed that there is a tendency that DCI >7000 mmHg.cm.s may represent the lower limit of hypercontractility, and when <700 mmHg.cm.s (<5% percentile) interpreted as ineffective esophageal motility or failcontraction. Also compared to Chicago 3.0, higher integrated relaxation pressure and duration of distal latency were found. We emphasize that these data must be confirmed by future studies.

Impact of prolonged 48-h wireless capsule esophageal pH monitoring on diagnosis of gastroesophageal reflux disease and evaluation of the relationship between symptoms and reflux episodes.

CONTEXT: Gastroesophageal reflux disease is one of the most common digestive diseases and an important cause of distress to patients. Diagnosis of this condition can require ambulatory pH monitoring. OBJECTIVES: To determine the diagnostic yield of a wireless ambulatory pH monitoring system of 48-hours, recording to diagnose daily variability of abnormal esophageal acid exposure and its symptom association. METHODS: A total of 100 consecutive patients with persistent reflux symptoms underwent wireless pH capsule placement from 2004 to 2009. The wireless pH capsule was deployed 5 cm proximal to the squamocolumnar junction after lower esophageal sphincter was manometrically determined. The pH recordings over 48-h were obtained after uploading data to a computer from the receiver that recorded pH signals from the wireless pH capsule. The following parameters were analyzed: (1) percentual time of distal esophageal acid exposure; (2) symptom association probability related to acid reflux. The results between the first and the second day were compared, and the diagnostic yield reached when the second day monitoring was included. RESULTS: Successful pH data over 48-h was obtained in 95% of patients. Nearly one quarter of patients experienced symptoms ranging from a foreign body sensation to chest pain. Forty-eight hours pH data analysis was statistically significant when compared to isolated analysis of day 1 and day 2. Study on day 2 identified seven patients (30.4%) that would be missed if only day 1 was analyzed. Three patients (18.7%) out of 16 patients with normal esophageal acid exposure on both days, showed positive symptom association probability, which generated an increase in diagnostic yield of 43.4%. CONCLUSION: Esophageal pH monitoring with wireless capsule is safe, well tolerated, does not require sedation. The extended 48-h period of study poses an increased yield to diagnose gastroesophageal reflux disease patients.

Impact of prolonged 48-h wireless capsule esophageal pH monitoring on diagnosis of gastroesophageal reflux disease and evaluation of the relationship between symptoms and reflux episodes / Impacto da monitorização prolongada do refluxo por pHmetria sem cateter por 48 horas, no diagnóstico da doença do refluxo gastroesofágico e no estudo da relação entre os sintomas e o refluxo

CONTEXT: Gastroesophageal reflux disease is one of the most common digestive diseases and an important cause of distress to patients. Diagnosis of this condition can require ambulatory pH monitoring. OBJECTIVES: To determine the diagnostic yield of a wireless ambulatory pH monitoring system of 48-hours, recording to diagnose daily variability of abnormal esophageal acid exposure and its symptom association. METHODS: A total of 100 consecutive patients with persistent reflux symptoms underwent wireless pH capsule placement from 2004 to 2009. The wireless pH capsule was deployed 5 cm proximal to the squamocolumnar junction after lower esophageal sphincter was manometrically determined. The pH recordings over 48-h were obtained after uploading data to a computer from the receiver that recorded pH signals from the wireless pH capsule. The following parameters were analyzed: (1) percentual time of distal esophageal acid exposure; (2) symptom association probability related to acid reflux. The results between the first and the second day were compared, and the diagnostic yield reached when the second day monitoring was included. RESULTS: Successful pH data over 48-h was obtained in 95 percent of patients. Nearly one quarter of patients experienced symptoms ranging from a foreign body sensation to chest pain. Forty-eight hours pH data analysis was statistically significant when compared to isolated analysis of day 1 and day 2. Study on day 2 identified seven patients (30.4 percent) that would be missed if only day 1 was analyzed. Three patients (18.7 percent) out of 16 patients with normal esophageal acid exposure on both days, showed positive symptom association probability, which generated an increase in diagnostic yield of 43.4 percent. CONCLUSION: Esophageal pH monitoring with wireless capsule is safe, well tolerated, does not require sedation. The extended 48-h period of study poses an increased yield to diagnose gastroesophageal reflux disease patients.

CONTEXTO: A doença do refluxo gastroesofágico é uma das doenças digestivas mais comuns e importante causa de desconforto para os pacientes. O diagnóstico desta condição clínica pode requerer monitoramento ambulatorial do pH esofágico. OBJETIVOS: Determinar o espectro diagnóstico do sistema de monitoramento ambulatorial do pH esofágico com cápsula telemétrica por um período de 48 horas no diagnóstico da variabilidade diária da exposição ácida anormal e sua associação com sintomas. MÉTODOS: Foram incluídos 100 pacientes adultos, consecutivos, com sintomas relacionados com a doença do refluxo gastroesofágico, que realizaram pHmetria com cápsula telemétrica por 48 horas entre 2004 e 2009. A cápsula foi posicionada e implantada a 5 cm da borda superior do esfíncter esofágico inferior, definida pela manometria esofágica. Foram analisados os seguintes parâmetros: (1) tempos percentuais de exposição ácida no esôfago distal; (2) probabilidade de associação dos sintomas com o refluxo ácido. Foram comparados os resultados entre o 1º e o 2º dia de monitoramento, assim como o eventual ganho diagnóstico obtido após a inclusão do 2º dia no monitoramento. RESULTADOS: Sucesso na obtenção dos dados do pH esofágico durante 48 horas foi obtido em 95 por cento dos pacientes. Aproximadamente 25 por cento dos pacientes apresentaram sintomas relacionados à implantação da cápsula, variando entre sensação de presença de corpo estranho à dor torácica. A análise dos resultados do estudo de 48 horas mostrou-se estatisticamente significante quando comparada com as análises isoladas do dia 1 e do dia 2. O estudo do dia 2 identificou sete pacientes (30.4 por cento) que teriam sido perdidos se somente o dia 1 fosse analisado. Três pacientes (18.7 por cento) dos 16 pacientes com exposição ácida normal no esôfago distal em ambos os dias, apresentaram probabilidade de associação com o sintoma positivo, que gerou incremento no ganho diagnóstico com este método diagnóstico de 43.4 por cento. CONCLUSÕES: O monitoramento do pH esofágico com a cápsula telemétrica é seguro, bem tolerado e não requer sedação. A extensão do período de estudo para 48 horas representa significativo aumento no ganho diagnóstico em pacientes com doença do refluxo gastroesofágico.

[Non-cardiac chest pain]. / Dor torácica não-cardiogênica.

CONTEXT: Non-cardiac chest pain or functional chest pain is a syndrome with high prevalence in occidental world. Findings on 15%-30% of coronary angiograms performed in patients with chest pain are normal. Causes significant impact in quality of life of patients and is associated with increased use of the health care facilities. DATA SOURCES: To this review the following data base were accessed: Medline, the Cochrane Library, LILACS. The limit was the last 5 years publications and were selected relevant original articles, reviews, consensus, guidelines and meta-analysis. RESULTS: Forty-four papers were selected, 28 original articles, 12 reviews, 2 guidelines, 1 consensus and 1 meta-analysis. CONCLUSIONS: Exclusion of cardiac disease is of crucial importance. On the other hand non-cardiac chest pain could be related to gastrointestinal, muscular and respiratory causes and/or psychological disturbances. Treatment aims to attack mechanism generator in order to relieve or to eliminate symptoms. Drugs are the cornerstone of treatment, exception to achalasia patients because those have better response to dilation of the esophagus or surgery, and to those who need intensive psychological therapy. The most important drugs used are proton pump inhibitors and tricyclic antidepressants, the latter, to modulate central signal process (visceral hypersensitivity) and autonomic response. Recently, new diagnostic facilities, and also therapeutic modalities, such as esophageal botulin toxin injection and hypnosis are under investigations. In the near future, maybe some of them would take a place in the therapeutic scenario of these patients.

Dor torácica não-cardiogênica: [revisão] / Non-cardiac chest pain: [review]

CONTEXTO: Dor torácica não-cardiogênica ou dor torácica funcional é síndrome clínica com elevada prevalência no mundo ocidental, podendo estar presente entre 15 por cento a 30 por cento dos pacientes com coronariografias normais. Tem importante impacto na qualidade de vida dos pacientes e associa-se com considerável aumento da utilização dos serviços de saúde. FONTES DE INFORMAÇÃO: Para esta revisão, foram utilizadas as seguintes bases de dados: Medline, the Cochrane Library, LILACS e livros nacionais. Das publicações dos últimos 5 anos foram selecionadas fontes relevantes como artigos originais, artigos de revisão, consensos, diretrizes e revisões sistemáticas de literatura com meta-análise. Publicações relevantes anteriores ao período de tempo analisado, foram também incluídas. RESULTADOS: Foram incluídas 44 publicações, sendo 28 artigos originais, 12 trabalhos de revisão, 2 diretrizes, 1 meta-análise e 1 consenso. CONCLUSÕES: A dor torácica não-cardiogênica abrange a investigação do trato digestório, do aparelho musculoesquelético, do aparelho respiratório e de distúrbios psicológicos. O objetivo do tratamento é o alívio ou eliminação do sintoma e deve estar voltado para o principal mecanismo gerador. A base do tratamento é medicamentosa, entretanto, pode ser necessária intervenção de natureza psicológica e, nos pacientes com acalásia a terapia endoscópica ou cirúrgica. Considerando-se que a maioria dos pacientes apresentarão causas relacionadas ao esôfago, sendo as principais, a doença do refluxo gastroesofágico e distúrbios motores, as principais medicações utilizadas no controle da dor torácica não-cardiogênica são os inibidores da bomba de prótons e os antidepressivos tricíclicos. Recentemente, novas modalidades diagnósticas e também formas de tratamento, tais como, a injeção por endoscopia de toxina botulínica no esôfago e a hipnose, estão em investigação e algumas poderão ocupar lugar no cenário do tratamento destes pacientes.

CONTEXT: Non-cardiac chest pain or functional chest pain is a syndrome with high prevalence in ocidental world. Findings on 15 percent-30 percent of coronary angiograms performed in patients with chest pain are normal. Causes significant impact in quality of life of patients and is associated with increased use of the health care facilities. DATA SOURCES: To this review the following data base were accessed: Medline, the Cochrane Library, LILACS. The limit was the last 5 years publications and were selected relevant original articles, reviews, consensus, guidelines and meta-analysis. RESULTS: Forty-four papers were selected, 28 original articles, 12 reviews, 2 guidelines, 1 consensus and 1 meta-analysis. CONCLUSIONS: Exclusion of cardiac disease is of crucial importance. On the other hand non-cardiac chest pain could be related to gastrointestinal, muscular and respiratory causes and/or psychological disturbances. Treatment aims to attack mechanism generator in order to relieve or to eliminate symptoms. Drugs are the cornerstone of treatment, exception to achalasia patients because those have better response to dilation of the esophagus or surgery, and to those who need intensive pyschological therapy. The most important drugs used are proton pump inhibitors and triciclic antidepressants, the latter, to modulate central signal process (visceral hypersensitivity) and autonomic response. Recently, new diagnostic facilities, and also therapeutic modalities, such as esophageal botulin toxin injection and hypnosis are under investigations. In the near future, maybe some of them would take a place in the therapeutic scenario of these patients.

Technological insights: combined impedance manometry for esophageal motility testing-current results and further implications.

This review focuses on current aspects of the novel technology of combined impedance manometry for esophageal motility testing. It presents methodological features, summarizes current results and discusses implications for further research. The combined technique assesses simultaneously bolus transport and associated peristalsis, thus allowing detailed analysis of the relationships between bolus transit and esophageal motility. Recent studies demonstrate that combined impedance manometry provides important additional information about esophageal motility as compared to conventional manometry: (1) monitoring of bolus transport patterns, (2) calculation of bolus transit parameters, (3) evaluation of bolus clearance, (4) monitoring of swallow associated events such as air movement and reflux, and (5) investigation of the relationships between bolus transit and LES relaxation. Studies with healthy subjects have identified several useful parameters for comprehensive assessment of eosphageal function. These parameters were found to be pathological in patients with classical achalasia, mild GERD, and ineffective esophageal motility. The technology of combined impedance manometry provides an important new tool for esophageal function testing, advancing both clinical and basic research. However, several important issues remain to be standardized to make the technique suitable for widely clinical use.

Postprandial transduodenal bolus transport is regulated by complex peristaltic sequence.

AIM: To study the relationship between the patterns of postprandial peristalsis and transduodenal bolus transport in healthy subjects. METHODS: Synchronous recording of chyme transport and peristaltic activity was performed during the fasting state and after administration of a test meal using a special catheter device with cascade configuration of impedance electrodes and solid-state pressure transducers. The catheter was placed into the duodenum, where the first channel was located in the first part of the duodenum and the last channel at the duodenojejunal junction. After identification of previously defined chyme transport patterns the associated peristaltic patterns were analyzed. RESULTS: The interdigestive phase 3 complex was reliably recorded with both techniques. Of 497 analyzed impedance bolus transport events, 110 (22%) were short-spanned propulsive, 307 (62%) long-spanned propulsive, 70 (14%) complex propulsive, and 10 (2%) retrograde transport. Short-spanned chyme transports were predominantly associated with stationary or propagated contractions propagated over short distance. Long-spanned and complex chyme transports were predominantly associated with propulsive peristaltic patterns, which were frequently complex and comprised multiple contractions. Propagated double wave contraction, propagated contraction with a clustered contraction, and propagated cluster of contractions have been identified to be an integralted part of a peristaltic sequence in human duodenum. CONCLUSION: Combined impedancometry and manometry improves the analysis of the peristaltic patterns that are associated with postprandial transduodenal chyme transport. Postprandial transduodenal bolus transport is regulated by propulsive peristaltic patterns, which are frequently complex but well organized. This finding should be taken into consideration in the analysis of intestinal motility studies.

Hemorragia digestiva alta não-varicosa: diagnóstico e tratamento / Upper nonvariceal gastrointestinal bleeding: diagnosis and treatment

A hemorragia digestiva alta aguda não-varicosa, que tem como principal causa a doença ulceropéptica, continua sendo uma das principais emergências médicas, ocorrendo, sobretudo, em pacientes idosos. A avaliação clínica é aspecto importante na estratificação do risco de mortalidade e ressangramento, este também sendo influenciado pelos achados endoscópicos. Além das medidas gerais que serão adotadas para todos os pacientes acometidos por esta síndrome clínica, existem três modalidades terapêuticas que podem ser praticadas: o tratamento endoscópico, o angiográfico e o cirúrgico. A modalidade endoscópica é a mais freqüentemente utilizada, controlando o sangramento ativo em mais de 90 por cento dos casos, reduzindo significativamente as taxas de ressangramento, a necessidade de hemotransfusões, custos hospitalares e cirurgia de urgência].

Manifestaçöes clínicas dos distúrbios motores esofagianos / Clinical presentation of esophageal motor disorders

Os distúrbios motores esofagianos representam uma disfunçäo da motilidade do órgäo com alteraçöes na peristalse do corpo esofagiano e/ou no funcionamento dos seus esfíncteres. Apresentam como principais sintomas, disfagia e dor torácica, por vezes com características semelhantes àquelas observadas quando há o comprometimento orgânico do esôfago. Portanto, o reconhecimento do seu quadro clínico é importante para o diagnóstico diferencial com outras enfermidades e para o adequado tratamento dos pacientes.(au)

Síndrome da angústia respiratória do adulto: novos conceitos e tratamento atual / Respiratory agony syndrome: new concepts and current treatment

Os autores revisam os critérios utilizados para definiçäo de injúria pulmonar aguda (IPA) e de síndrome de angústia respiratória do adulto (SARA). Säo também apresentados os novos conceitos fisiopatológicos destas síndromes, bem como suas implicaçöes na avaliaçäo de cada caso. Finalizando, säo discutidas as formas de tratamento atualmente utilizadas na SARA.