Pathophysiological aspects of nephropathy caused by non-steroidal anti-inflammatory drugs / Aspectos fisiopatológicos da nefropatia por anti-inflamatórios não esteroidais

Abstract Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used medications associated with nephrotoxicity, especially when used chronically. Factors such as advanced age and comorbidities, which in themselves already lead to a decrease in glomerular filtration rate, increase the risk of NSAID-related nephrotoxicity. The main mechanism of NSAID action is cyclooxygenase (COX) enzyme inhibition, interfering on arachidonic acid conversion into E2 prostaglandins E2, prostacyclins and thromboxanes. Within the kidneys, prostaglandins act as vasodilators, increasing renal perfusion. This vasodilatation is a counter regulation of mechanisms, such as the renin-angiotensin-aldosterone system works and that of the sympathetic nervous system, culminating with compensation to ensure adequate flow to the organ. NSAIDs inhibit this mechanism and can lead to acute kidney injury (AKI). High doses of NSAIDs have been implicated as causes of AKI, especially in the elderly. The main form of AKI by NSAIDs is hemodynamically mediated. The second form of NSAID-induced AKI is acute interstitial nephritis, which may manifest as nephrotic proteinuria. Long-term NSAID use can lead to chronic kidney disease (CKD). In patients without renal diseases, young and without comorbidities, NSAIDs are not greatly harmful. However, because of its dose-dependent effect, caution should be exercised in chronic use, since it increases the risk of developing nephrotoxicity.

Resumo Os anti-inflamatórios não esteroidais (AINEs) são medicamentos comumente utilizados, associados à nefrotoxicidade, sobretudo quando utilizados cronicamente. Fatores como idade avançada e comorbidades, que por si só já levam à diminuição da taxa de filtração glomerular, aumentam o risco de nefrotoxicidade dos AINEs. O principal mecanismo de ação dos AINEs é a inibição da enzima ciclooxigenase (COX), interferindo na conversão do ácido araquidônico em prostaglandinas E2, prostaciclinas e tromboxanos. Nos rins, as prostaglandinas atuam como vasodilatadoras, aumentando a perfusão renal. Essa vasodilatação atua como uma contrarregulação de mecanismos, como a atuação do sistema renina-angiotensina-aldosterona e do sistema nervoso simpático, culminando com uma compensação para assegurar o fluxo adequado ao órgão. O uso de AINEs inibe esse mecanismo, podendo causar lesão renal aguda (LRA). Altas doses de AINEs têm sido implicadas como causas de LRA, especialmente em idosos. A principal forma de LRA por AINEs é a hemodinamicamente mediada. A segunda forma de apresentação da LRA induzida por AINES é a nefrite intersticial aguda, que pode se manifestar com proteinúria nefrótica. O uso de AINEs em longo prazo pode ocasionar doença renal crônica (DRC). Nos pacientes sem doenças renais, jovens e sem comorbidades, os AINEs não apresentam grandes malefícios. Entretanto, por seu efeito dose-dependente, deve-se ter grande cautela no uso crônico, por aumentar risco de desenvolver nefrotoxicidade.

Inhibitory effects on the production of inflammatory mediators and reactive oxygen species by Mori folium in lipopolysaccharide-stimulated macrophages and zebrafish

ABSTRACT Mori folium, the leaf of Morus alba L. (Moraceae), has been traditionally used for various medicinal purposes from ancient times to the present. In this study, we examined the effects of water extract of Mori folium (WEMF) on the production of inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), and reactive oxygen species (ROS) in lipopolysaccharide (LPS)-stimulated murine RAW 264.7 macrophages. Our data indicated that WEMF significantly suppressed the secretion of NO and PGE2 in RAW 264.7 macrophages without any significant cytotoxicity. The protective effects were accompanied by a marked reduction in their regulatory gene expression at the transcription level. WEMF attenuated LPS-induced intracellular ROS production in RAW 264.7 macrophages. It inhibited the nuclear translocation of the nuclear factor-kappa B p65 subunit and the activation of mitogen-activated protein kinases in LPS-treated RAW 264.7 macrophages. Furthermore, WEMF reduced LPS-induced NO production and ROS accumulation in zebrafish. Although more efforts are needed to fully understand the critical role of WEMF in the inhibition of inflammation, the findings of the present study may provide insights into the approaches for Mori folium as a potential therapeutic agent for inflammatory and antioxidant disorders.

A vigilância e o monitoramento das principais doenças crônicas não transmissíveis no Brasil - Pesquisa Nacional de Saúde, 2013 / Surveillance and monitoring of major chronic diseases in Brazil - National Health Survey, 2013

RESUMO: Objetivo: Descrever as principais doenças crônicas não transmissíveis (DCNT) no país segundo as informações coletadas em indivíduos de 18 anos ou mais de idade. Métodos: Foram utilizados dados da Pesquisa Nacional de Saúde (PNS), 2013, estudo transversal de base populacional. As proporções de cada DCNT foram calculadas e apresentadas segundo sexo, com intervalo de confiança de 95% (IC95%), com os valores absolutos. Resultados: Do total de entrevistados, 45,1% referiram ter pelo menos uma DCNT. A Região com maior prevalência de DCNT foi a Sul (52,1%). A hipertensão arterial apresentou a maior prevalência dentre as DCNT, com 21,4%, seguida por problema crônico de coluna (18,5%), depressão (7,6%), artrite (6,4%) e diabetes (6,2%). O grau de limitação intenso/muito intenso apresentou maiores prevalências para outra doença mental (37,6%) e acidente vascular cerebral (AVC) (25,5%). Conclusão: A melhoria dos serviços de saúde é indispensável para uma resposta efetiva à dupla carga de adoecimento de países de média e baixa renda.

ABSTRACT: Objective: To describe the major noncommunicable diseases (NCDs) in Brazil, according to the information collected from individuals aged 18 years or older. Methods: Data from the National Health Survey (PNS), 2013, a transversal population-based study, were used. The proportions of each NCD were calculated and presented according to sex, with a 95% confidence interval (95%CI), with the absolute values. Results: Of the total respondents, 45.1% reported presenting at least one NCD. The region with the highest prevalence of NCDs was the South (52.1%). Hypertension showed the highest prevalence among NCDs, with 21.4%, followed by chronic back problem (18.5%), depression (7.6%), arthritis (6.4%), and diabetes (6.2%). The intense/very intense degree of limitation showed a higher prevalence of other mental illnesses (37.6%) and cerebrovascular accident (25.5%). Conclusion: The improvement of health services is essential for an effective response to the double burden of illness in the middle- and low-income countries.

Prostaglandin catabolism and ulcerative colitis: effect of sulphasalazine, 5-aminosalicylic acid and other drugs

1. Evidence is presented for the occurrence of type 1 prostaglandin 15-hidroxydehydrogenase in human rectal mucosa. No evidence of the presence of type 2 dnzyme was found. 2. A 15-keto-prostaglandin reductase, responsible for the breakdown of 13, 14-dihydro 15-keto prostaglandins to 13, 14-dihydro prostaglandins, was also present in human rectal mucosa. 3. Ulcerative colitis patients catabolized prostaglandins to the same extent as the control group. PGE was catabolized significantly better than PGF2 alfa. 4. 5-Aminosalicylic acid and sulphapyridine did not affect prostaglandin catabolism. Sulphasalazine, methilsulphasalazine, indomethacin, flurbiprofen, disodium cromoglycate, sodium salicylate and carbenoxolone sodium inhibited prostaglandin catabolism to the same extent in both groups.Salicylazosulphadimidine was a more potent inhibitor of PGE1 catabolism than of PGF2alfa. 5. The increased prostaglandin synthesis reported for ulcerative colitis patients was not paralleled by increased catabolism, a fact possibly contributing to the accumulation of such compounds in the diseased state