Hydrogen sulfide in posthemorrhagic shock mesenteric lymph drainage alleviates kidney injury in rats

Posthemorrhagic shock mesenteric lymph (PHSML) is a key factor in multiple organ injury following hemorrhagic shock. We investigated the role of hydrogen sulfide (H2S) in PHSML drainage in alleviating acute kidney injury (AKI) by administering D,L-propargylglycine (PPG) and sodium hydrosulfide hydrate (NaHS) to 12 specific pathogen-free male Wistar rats with PHSML drainage. A hemorrhagic shock model was established in 4 experimental groups: shock, shock+drainage, shock+drainage+PPG (45 mg/kg, 0.5 h prehemorrhage), and shock+drainage+NaHS (28 µmol/kg, 0.5 h prehemorrhage). Fluid resuscitation was performed after 1 h of hypotension, and PHMSL was drained in the last three groups for 3 h after resuscitation. Renal function and histomorphology were assessed along with levels of H2S, cystathionine-γ-lyase (CSE), Toll-like receptor 4 (TLR4), interleukin (IL)-10, IL-12, and tumor necrosis factor (TNF)-α in renal tissue. Hemorrhagic shock induced AKI with increased urea and creatinine levels in plasma and higher H2S, CSE, TLR4, IL-10, IL-12, and TNF-α levels in renal tissue. PHSML drainage significantly reduced urea, creatinine, H2S, CSE, and TNF-α but not TLR4, IL-10, or IL-12. PPG decreased creatinine, H2S, IL-10, and TNF-α levels, but this effect was reversed by NaHS administration. In conclusion, PHSML drainage alleviated AKI following hemorrhagic shock by preventing increases in H2S and H2S-mediated inflammation.

Tratamento do Mieloma Múltiplo recidivado / Relapsed Multiple Myeloma treatment

O mieloma múltiplo ainda é uma doença incurável. Apesar das novas estratégias de tratamento, a maioria dos pacientes recidiva. O padrão da recidiva é muito heterogêneo, podendo se apresentar com comportamento indolente ou agressivo. O tratamento da doença recidivada depende de vários fatores: do tratamento realizado como primeira linha, se transplante autólogo de medula óssea ou não, da resposta e sua duração, se a recidiva ocorreu com ou sem tratamento de manutenção, do performance status do paciente e da reserva medular. Se a recidiva ocorrer após seis meses do término do tratamento, o mesmo esquema quimioterápico inicial pode ser instituído. O transplante autólogo de medula óssea pode ser proposto como consolidação em recidivas quimiossensíveis ou como tratamento de resgate, se as células-tronco periféricas tiverem sido coletadas anteriormente. A talidomida tem sido utilizada em pacientes com mieloma múltiplo recidivado após quimioterapia convencional ou após o transplante autólogo da medula óssea. A talidomida sozinha pode induzir respostas objetivas em pelo menos 1/3 dos pacientes que já receberam muitos tratamentos; e quando combinada com quimioterapia, as respostas objetivas ocorrem em aproximadamente 2/3 dos pacientes. O bortezomibe está indicado em pacientes recidivados, sozinho ou associado a dexametasona e a outras drogas, com taxas de resposta de 43 por cento a 76 por cento. O melhor tratamento do paciente com mieloma múltiplo recidivado deve ser individualizado, dependendo da idade, da função da medula óssea, da terapia inicial, do padrão e tempo para a recidiva.

Multiple myeloma still remains an incurable disease. Despite the new treatment approaches, almost all patients face the risk of an eventual relapse. The pattern of relapse is very heterogeneous and can be indolent or more aggressive. The treatment of relapsed disease depends on a number of factors: duration of response, relapse on or off maintenance therapy, prior therapy and specially prior autologous stem cell transplantation, performance status, hematopoietic reserve. If relapse occurs more than 6 months after therapy ended, the initial chemotherapy regimen should be reinstituted. Autologous stem cell transplantation can be proposed as consolidation therapy in chemosensitive relapses or as salvage therapy if stem cells have been collected earlier. Thalidomide has been tested in relapsed multiple myeloma and is now considered as standard treatment for patients relapsing after conventional chemotherapy or after autologous stem cell transplantation. Thalidomide alone can induce objective responses in at least one-third of heavily pretreated patients and, combined with chemotherapy, objective responses can be achieved by two-thirds of the patients. Bortezomib is indicated, alone or in combination with other agents, for relapsed patients and can produce an overall response rate of 43 percent to 76 percent. The most appropriate management must be individualized depending on the age, bone marrow function, prior therapy and the timing of the relapse.