Luiz Alberto Benvenuti

Resveratrol (RSV) improves metabolic functions, but its tissue-specific effects on diabetes remain unclear. This study investigated RSV’s impact on molecular pathways in an experimental model of diabetes in cardiac and skeletal muscles and adipose tissue. Wistar rats were assigned to control (C), control treated with RSV (RC), diabetic (D), and diabetic treated with RSV (RD). Diabetes was induced using streptozotocin and nicotinamide, and RSV was administered for six weeks. In diabetic rats, RSV treatment significantly reduced collagen accumulation in cardiac and skeletal muscle tissues compared to untreated diabetic controls, although it did not restore muscle mass. Adipose tissue in diabetic rats exhibited a significant reduction of 3.4 times in collagen levels following RSV treatment. However, this reduction was not associated with any measurable improvement in tissue function. In cardiac tissue, RSV downregulated phosphorylated protein kinase B (AKT)/AKT and phosphorylated ribosomal protein S6 (rpS6)/rpS6 while mammalian target of rapamycin (mTOR) activity remained unchanged. In skeletal muscle, RSV suppressed rpS6 phosphorylation without affecting (mTOR) signaling. RSV enhanced mTOR and Beclin-1 expression in adipose tissue, though metabolic dysfunction persisted. RSV reduced receptors for advanced glycation end-product expression in all tissues, indicating the modulation of hyperglycemia-driven pathways. RSV improved fibrosis and signaling pathways but failed to reverse abnormal tissue growth patterns, including cardiac hypertrophy, skeletal muscle atrophy, and adipose tissue atrophy.

Resveratrol (RSV) improves metabolic and cardiovascular functions, but its tissue-specific effects on diabetes remain unclear. This study investigated RSV's impact on cardiac and skeletal muscle and adipose tissue in a rat diabetes model. Thirty-two Wistar rats were assigned to four groups: control (C), control treated with RSV (RC), diabetic (D), and diabetic treated with RSV (RD). Diabetes was induced using streptozotocin and nicotinamide. After two weeks, RC and RD groups received RSV for six weeks. Histological and protein expression analyses were performed on cardiac, skeletal muscle, and visceral fat tissues. RSV significantly reduced collagen accumulation in diabetic cardiac and skeletal muscles compared to untreated diabetic rats. Adipose tissue in diabetic rats exhibited the most notable reduction in collagen levels following RSV treatment (D/C: 30.15, IQ: 9.66–50.36 vs. RD/C: 8.88, IQ: 4.86–19.06, p < 0.01).In cardiac tissue, RSV downregulated AKT and rpS6 phosphorylation. In skeletal muscle, RSV suppressed rpS6 phosphorylation and in adipose tissue, RSV enhanced mTOR and PPARα expression. RSV reduced receptor for advanced glycation end products expression across all examined tissues, indicating its role in modulating pathways driven by hyperglycemia. Although RSV improved fibrosis and signaling pathways, it did not reverse structural damage or metabolic dysfunction. These results highlight the need for further studies to refine RSV-based therapies for diabetes-induced tissue damage.

Autops Case Rep, vol.14, e2024513, 2024

Introdução A Síndrome Carcinoide (SC) é uma síndrome paraneoplásica frequentemente diagnosticada em pacientes com tumores neuroendócrinos (TNEs) associados com secreção de fatores humorais. Esses fatores incluem a serotonina (5-HT), a qual parece ser a substância mais comum associada à síndrome, além de histamina, calicreína, prostaglandinas e taquicininas. Entre os pacientes diagnosticados com TNEs localizados no duodeno e intestino delgado, cerca de 20% irão desenvolver SC durante o acompanahmento. A presença de SC está fortemente associada com maior grau e estágio [...] Introdução A Síndrome Carcinoide (SC) é uma síndrome paraneoplásica frequentemente diagnosticada em pacientes com tumores neuroendócrinos (TNEs) associados com secreção de fatores humorais. Esses fatores incluem a serotonina (5-HT), a qual parece ser a substância mais comum associada à síndrome, além de histamina, calicreína, prostaglandinas e taquicininas. Entre os pacientes diagnosticados com TNEs localizados no duodeno e intestino delgado, cerca de 20% irão desenvolver SC durante o acompanahmento. A presença de SC está fortemente associada com maior grau e estágio

Background: Chagas disease reactivation (CDR) after heart transplantation is characterized by relapse of the infectious disease with proliferation and dissemination of Trypanosoma cruzi parasites. Serial blood PCR testing is consensually recommended for CDR monitoring, but there is uncertainty about the incremental value in performing the molecular tests in endomyocardial biopsies (EMB).Methods: We compared qualitative and quantitative results of PCR for T cruzi DNA in 62 pairs of blood and EMB collected with a maximum time interval of 7 days, from 34 heart‐transplanted, chagasic patients.Results: Blood PCR resulted positive in 39/62 (62.9%) samples, with PL ranging from 0.14 to 1610.73 (median: 3.31). PCR resulted positive in 8/60 (13.3%) EMB, with PL ranging from 2.82 to 1670.55 (median: 65.63). All blood samples which tested negative presented a paired EMB which also tested negative. However, 31/39 (79.5%) blood samples which tested positive presented a paired EMB which tested negative. There was poor agreement between blood and EMB PCR (kappa = 0.153). CDR affecting the myocardium (myo‐CDR) was diagnosed in three occasions. PCR resulted positive in both blood and EMB at the time of myo‐CDR, with PL ranging from 0.61 to 1610.73 in blood and 13.8 to 1670.55 in EMB.Conclusions: Negative PCR for T cruzi in blood rules out myo‐CDR, with no value of testing EMB. Positive PCR in blood with high PL is diagnostic for myo‐CDR. If PCR in blood results positive with low PL, testing EMB is useful: negative PCR turns unlikely, and positive PCR reinforces greatly the possibility of myo‐CDR.

Após a alta hospitalar, evoluiu com dispneia de classe funcional IV (New York Heart Association), episódios esporádicos de dispneia paroxística noturna e ortopneia, e foi encaminhada para o InCor-HCFMUSP. Estava em uso de AAS, 100 mg/dia; furosemida 40mg, 3 vezes ao dia; captopril 50mg, 3 vezes ao dia; clopidogrel 75mg, 1 vez ao dia; sinvastatina 40mg, 1 vez ao dia.

Background: Reactivation of Chagas disease after heart transplantation is characterized by proliferation and dissemination of Trypanosoma cruzi parasites to several organs. Reactivation affecting the allograft can simulate acute cellular rejection, from which it should be distinguished through the analysis of endomyocardial biopsies (EMB).Methods: We evaluated retrospectively 100 EMB collected in the first year of follow‐up from 13 heart‐transplanted, chagasic patients who presented reactivation and were successfully treated. Additionally, 37 EMB from 8 patients who did not present reactivation constituted the control group. We reviewed histopathology and performed a real‐time PCR‐based assay in order to evaluate the T cruzi parasitic load of each EMB.Results: The parasitic load of the EMB at the time of reactivation ranged from 22.80 to 190 000/10⁶ cells (median: 1555). In 6 patients, none of the EMB obtained prior to reactivation amplified T cruzi DNA. On the other hand, 10 EMB from 7 patients, obtained 9‐105 days before reactivation (median: 26 days), showed parasitic load ranging from 8.25 to 625/10⁶ cells (median: 167.55). In all patients, the parasitic load increased at the time of reactivation, usually sharply. After initiation of treatment, all patients showed negative PCR or a dramatic reduction of the parasitic load in the following EMB. None of the EMB from the control group amplified T cruzi DNA.Conclusions: Sequential measurement of T cruzi parasitic load in EMB is useful for monitoring Chagas disease reactivation after heart transplantation. Its increase suggests imminent reactivation and its decrease after treatment indicates favorable evolution for cure of the episode of reactivation.