ABSTRACT
During a routine checkup in a 10-year-old male with Attention-Deficit Hyperactivity Disorder, blood pressure of 180/120 mmHg was found. Physical examination was completely normal. Ultrasound examination showed poststenotic dilatation of the left renal artery which was confirmed by CT-angiography showing a short, high grade stenosis of the left renal artery. Percutaneous Transluminal Angioplasty of the stenosis was not successful and therefore the stenosis was excised with reimplantation of the renal artery in the aorta. Pathological examination of the excised segment showed media-type Fibromuscular Dysplasia (FMD). Six years after surgery, the kidney is completely normal regarding size and function. There are no signs of restenosis of the left renal artery. Nevertheless, the hypertension remained although less severe and requiring less medication.
ABSTRACT
The complement system plays an important role in the activation of the inflammatory response to injury, although inappropriate complement activation (CA) can lead to severe tissue damage. Maggot therapy is successfully used to treat infected wounds. In this study, we hypothesized that maggot excretions/secretions influence CA in order to modulate the host's inflammatory response. Therefore, the effect of maggot excretions on CA was investigated in preoperatively and postoperatively obtained sera from patients. Our results show that maggot excretions reduce CA in healthy and postoperatively immune-activated human sera up to 99.9%, via all pathways. Maggot excretions do not specifically initiate or inhibit CA, but break down complement proteins C3 and C4 in a cation-independent manner and this effect proves to be temperature tolerant. This study indicates a CA-reducing substrate that is already successfully used in clinical practice and may explain part of the improved wound healing caused by maggot therapy. Furthermore, the complement activation-reducing substance present in maggot excretions could provide a novel treatment modality for several diseases, resulting from an (over)active complement system.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Complement C3/immunology , Complement C4/immunology , Debridement/methods , Larva , Wound Healing , Wound Infection/therapy , Wounds and Injuries/therapy , Adult , Aged , Animals , Chronic Disease , Complement C3b/immunology , Complement C3d/immunology , Female , Humans , Immunity, Innate , Lymphocyte Activation , Male , Middle Aged , Peptide Fragments/immunology , Pilot Projects , Signal Transduction , Wound Healing/immunology , Wound Infection/immunology , Wound Infection/pathology , Wounds and Injuries/immunology , Wounds and Injuries/pathologyABSTRACT
Cold perfusion through the renal arteries during renal ischemia has been suggested to diminish postoperative renal damage after juxtarenal aortic aneurysm repair. As the kidneys play a key role in dimethylarginine metabolism, which in turn is associated with renal hemodynamics, we hypothesized that the protective effect of cold perfusion is associated with a preserved renal extraction of dimethylarginines. Renal ischemia was induced in three groups of anesthetized Wistar rats (n = 7/group), which underwent suprarenal aortic clamping (45 min) with no perfusion (group 1), renal perfusion with 37°C saline (group 2), or renal perfusion with 4°C saline (group 3), respectively, followed by 90 min of renal reperfusion in all groups. The sham group had no clamping. In group 3 (renal ischemia with cold perfusion), postoperative serum creatinine levels as well as the presence of luminal lipocalin-2 and its associated brush-border damage were lower compared with groups 1 and 2 (P < 0.05). Also, renal extraction of asymmetrical (ADMA) and symmetrical (SDMA) dimethylarginine as well as the arginine/ADMA ratio, which defines the bioavailability of nitric oxide, remained intact in group 3 only (P < 0.04). The arginine/ADMA ratio correlated with cortical flow, lipocalin-2, and creatinine rises. Warm and cold renal perfusion (groups 2 and 3) during ischemia were similarly effective in lowering protein nitrosylation levels, renal leukocyte accumulation, neutrophil gelatinase-associated lipocalin (NGAL) expression in distal tubules, and urine NGAL (P < 0.05). These data support the use of cold renal perfusion during renal ischemia in situations where renal ischemia is inevitable, as it reduces tubular damage and preserves renal extraction of dimethylarginines. Renal perfusion with saline per se during renal ischemia is effective in diminishing renal leukocyte accumulation and oxidative stress.
