ABSTRACT
The nephrotic syndrome holds significant clinical importance and is characterized by a substantial protein loss in the urine. Damage to the glomerular basement membrane or podocytes frequently underlies renal protein loss. There is an increasing belief in the involvement of the complement system, a part of the innate immune system, in these conditions. Understanding the interactions between the complement system and glomerular structures continually evolves, challenging the traditional view of the blood-urine barrier as a passive filter. Clinical studies suggest that a precise inhibition of the complement system at various points may soon become feasible. However, a thorough understanding of current knowledge is imperative for planning future therapies in nephrotic glomerular diseases such as membranous glomerulopathy, membranoproliferative glomerulonephritis, lupus nephritis, focal segmental glomerulosclerosis, and minimal change disease. This review provides an overview of the complement system, its interactions with glomerular structures, and insights into specific glomerular diseases exhibiting a nephrotic course. Additionally, we explore new diagnostic tools and future therapeutic approaches.
ABSTRACT
We report on seizures during anesthesia induction in animals treated with a cannabinoid receptor 1 (CB1R) antagonist for experimental sepsis. Animals received surgery for colon ascendens stent peritonitis-induced sepsis or sham surgery followed by treatment of CB1R antagonist, CB1R agonist, or placebo. Fourteen hours later, animals received pentobarbital or ketamine for anesthesia induction and animal behavior was observed. Tonic-clonic seizures were observed in 5 of 12 septic animals (42%) treated with CB1R antagonist after induction of anesthesia with pentobarbital. The data suggest that CB1R inhibition in combination with pentobarbital may increase the incidence of anesthetic-induced seizures in the case of sepsis.
Subject(s)
Anesthesia/adverse effects , Epilepsy, Tonic-Clonic/etiology , Hypnotics and Sedatives/toxicity , Morpholines/toxicity , Pentobarbital/toxicity , Pyrazoles/toxicity , Receptor, Cannabinoid, CB1/antagonists & inhibitors , Sepsis/complications , Sepsis/drug therapy , Animals , Arachidonic Acids/pharmacology , Behavior, Animal/drug effects , Disease Models, Animal , Epilepsy, Tonic-Clonic/metabolism , Epilepsy, Tonic-Clonic/psychology , Male , Rats , Rats, Inbred Lew , Receptor, Cannabinoid, CB1/agonists , Receptor, Cannabinoid, CB1/metabolism , Sepsis/metabolism , Time FactorsABSTRACT
INTRODUCTION: Cannabinoid receptor 2 (CB2R) expression is upregulated during sepsis. However, there are conflicting results regarding the effects of CB2R modulation in the hyperinflammatory phase of the disease. The aim of this study was therefore to investigate the effects of CB2R manipulation on leukocyte activation within the intestinal microcirculation in two acute experimental sepsis models. METHODS: In the endotoxemia model we studied four groups of Lewis rats: controls, lipopolysaccharide (LPS), LPS + CB2R agonist HU308 (2.5 mg/kg), and LPS + CB2R antagonist AM630 (2.5 mg/kg). In the colon ascendens stent peritonitis (CASP)-induced sepsis model we also studied four groups: sham group, CASP and CASP + CB2R agonist (HU308, 2.5 or 10 mg/kg). Intravital microscopy was performed 2 hours following LPS/placebo administration or 16 hours following CASP/sham surgery to quantify intestinal leukocyte recruitment. Additionally, hemodynamic monitoring, histological examinations and measurements of inflammatory mediators were performed. RESULTS: HU308 administration significantly reduced intestinal leukocyte adhesion in both acute sepsis models. The systemic levels of inflammatory mediators were significantly reduced by 10 mg/kg HU308 treatment in CASP animals. CONCLUSION: CB2R activation reduces leukocyte activation and systemic release of inflammatory mediators in acute experimental sepsis. Drugs targeting the CB2R pathway may have therapeutic potential in sepsis.