Increasing evidence indicates that mitochondrial dysfunction plays an important role in modulating the development of septic shock. In the present study, we investigated whether continuous veno-venous haemofiltration (CVVH) with high-volume might improve myocardial mitochondrial dysfunction in a porcine model of peritonitis-induced septic shock. Sixteen male Landrace pigs weighing 31±5 kg were randomly assigned to normal control group (n=4), peritonitis group (n=6) and peritonitis plus CVVH group (n=6). All animals were anaesthetised and mechanically ventilated. After baseline examinations, the peritonitis group and the peritonitis plus CVVH group underwent induction of peritonitis. One hour later, the animals in the peritonitis plus CVVH group received treatment with high-volume CVVH. Twelve hours after treatment, the animals were sacrificed. Animals in the peritonitis group were killed 13 hours after induction of peritonitis. Peritonitis challenge induced septic shock associated with increased blood lactate and high-volume CVVH improved lactate acidosis. Compared with the peritonitis group, cardiac output, stroke volume and mean arterial pressure were better maintained in peritonitis plus CVVH group. More importantly, high-volume CVVH improved myocardial mitochondrial complex I activity (0.22±0.03 vs. 0.15±0.04, P=0.04). These results suggest that high-volume CVVH improves haemodynamics and heart dysfunction in septic shock and the improvement may be attributed to amelioration of myocardial mitochondrial dysfunction.
Some high-risk patients with end-stage renal disease (ESRD) cannot tolerate or do not respond to conventional haemodialysis three times per week. Sixteen high-risk ESRD patients were converted from conventional haemodialysis to short daily haemodialysis (sDHD). This consisted of 2 h daily haemofiltration or haemodiafiltration, six times per week. The dialysis response, blood pressure change, weight variations, weekly Kt/V (a measure of the adequacy of dialysis), serum phosphorus, serum albumin, haemoglobin, cardiothoracic ratio (CTR), left ventricular mass index (LVMI) and Short Form Health Survey (SF-36) quality-of-life scales were compared before and after conversion to sDHD. sDHD improved many clinical and biological variables. Weekly Kt/V increased from 4.36 +/- 0.62 on conventional haemodialysis to 4.88 +/- 0.41 after switching to sDHD. Blood pressure normalized, there were significant decreases in episodes of hypotension during haemodialysis, serum phosphorus concentration, CTR and LVMI, and there were significant increases in levels of serum albumin and haemoglobin. Calcium and phosphorus metabolism, and nutritional status were improved. Physical function, physical role, bodily pain, general health, vitality and mental health improved significantly.
Summary
NOD‐like receptor pyrin 7 (NLRP7) has been identified as the major gene responsible for the recurrent hydatidiform mole (RHM). The immunological role of NLRP7 mutation in HM patients has not been conclusively demonstrated. Hence, we aim to demonstrate this role in our study. We followed 12 new patients with NLRP7 non‐synonymous variations (NSVs) from date to date. Peripheral blood mononuclear cells (PBMCs) were collected separately from patients with and without NLRP7 mutation. Supernatant interleukin (IL)‐1β secretion, intracellular pro‐IL‐1β and mature IL‐1β expressions were measured after 24 h lipopolysaccharide (LPS) stimulation. Plasmids with corresponding NSVs were generated to evaluate the ability of processing pro‐IL‐1β into mature IL‐1β in vitro. Homozygous or compound heterozygous NLRP7 mutations secreted less IL‐1β in roots of abnormal intracellular pro‐IL‐1β or mature IL‐1β, according to different domains. Plasmids with NSVs could also affect processing or/and trafficking together with caspase‐1 and apoptosis‐associated speck‐like protein (ASC). Inflammasome‐related NLRP7 mutation is a potential mechanism of RHM.
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