In order to study the mechanism by which an omental pedicle promotes healing when applied to an injured site, we injected a foreign body into the abdominal cavity to activate the omentum. One week after the injection, we isolated the omentum and measured blood vessel density, blood content, growth and angiogenesis factors (VEGF and others), chemotactic factors (SDF-1 alpha), and progenitor cells (CXCR-4, WT-1). We found that the native omentum, which consisted mostly of adipose tissue, expanded the mass of its non-adipose part (milky spots) 15- to 20-fold. VEGF and other growth factors increased by two- to four-fold, blood vessel density by three-fold, and blood content by two-fold. The activated omentum also showed increases in SDF-1 alpha, CXCR-4, and WT-1 cells (factors and cells positively associated with tissue regeneration). Thus, we propose that an omentum activated by a foreign body (or by injury) greatly expands its milky-spot tissue and becomes rich in growth factors and progenitor cells that facilitate the healing and regeneration of injured tissue.
We conclude that normally the kidney degrades large amounts of albumin and that the degradation fragments appear in the urine. These findings are in sharp contrast with the established view that degraded albumin is completely reabsorbed into the blood stream.
Cocaine causes acute hypertension by blocking catecholamine reuptake. There is evidence that it also impairs the peripheral endothelial nitric oxide system, which is normally vasodilatory. We further explored the role of nitric oxide in cocaine-induced vasoconstriction in anesthetized rats, and in vitro by using isolated carotid artery segments. Cocaine administered intravenously in rats increased mean arterial pressure by 30 to 40 mm Hg within 1 min. This effect was dose dependent and the maximum effect was observed at a dose of 1.25 mg/kg. The prototype catecholamine norepinephrine induced a similar increase in blood pressure. When rats were pretreated with NG-monomethyl-L-arginine (L-NMMA, a blocker of nitric oxide) and challenged with cocaine, the increase in blood pressure was blocked by 80%, whereas pretreatment with L-NMMA did not block norepinephrine-induced vasoconstriction. Both cocaine and norepinephrine also induced an immediate vasoconstriction in isolated carotid artery preparations. The in vitro vasoconstriction induced by cocaine was blocked by pretreatment with L-NMMA, whereas L-NMMA did not block the norepinephrine-induced vasoconstriction in vitro. Furthermore, carotid artery stripped of endothelium responded to norepinephrine but failed to respond to L-NMMA or cocaine. S-nitroso-N-acetyl-D,L-penicillamine (SNAP)-a precursor of nitric oxide- stimulated nitric oxide production in control coronary artery fragments. When these fragments were incubated with cocaine there was a 20% reduction in the production of nitrite oxide. These results suggest that cocaine exerts its peripheral vasoconstriction at least in part by inhibiting local vasodilator nitric oxide.
Background: Relaxin (Rlx), a 6-kD protein hormone, belongs to the insulin growth factor family. We have previously shown that Rlx reduces interstitial fibrosis in a model of chronic papillary necrosis. Hypothesis: The purpose of this study was to extend these observations to a model of renal injury induced by mass reduction. Material and Methods: Renal mass was reduced by either infarction or surgical excision of both poles, with removal of the contralateral kidney. Two weeks later, creatinine clearance was done and animals from both groups implanted with osmotic pumps delivering either Rlx (2 µg/h) or vehicle (Veh). Treatment was continued for 4 weeks. The severity of the glomerular injury was quantified by planimetric measurements. Renal function was assessed by creatinine clearance and plasma creatinine. Results: Rlx significantly decreased systolic blood pressure in animals with infarction. This was accompanied by a decrease in serum creatinine and a slight improvement in creatinine clearance. The severity of the glomerular lesion was reduced by Rlx (sclerosis index, Veh 1.16 ± 0.13 vs. Rlx 0.74 ± 0.16, p = 0.037). In the excision group the animals were normotensive. In this group, Rlx treatment was accompanied by a decrease in serum creatinine (Veh 1.01 ± 0.03 vs. Rlx 0.81 ± 0.05 mg/dl, p = 0.02) and an increase in GFR (Veh 0.90 ± 0.14 vs. Rlx 1.33 ± 0.11 ml/min, p = 0.03). The sclerosis index was also reduced. Conclusion: Rlx decreases renal injury by at least two mechanisms, one by lowering blood pressure as seen in the infarction model, the other independent of blood pressure as seen in the normotensive excision model where there was also a significant functional improvement.
Of 240 adults with sickle cell anemia seen over 11 years, 12 had the nephrotic syndrome. In 9 (75%) the glomerular lesion, sickle glomerulopathy, consisted of mesangial expansion and basement membrane duplication. Six patients had type IV renal tubular acidosis. Four of the 9 Patients died within 24 months (17 ± 5; mean ± SD), while 5 survived 36 months or longer (80 ± 49); no significant differences were seen between the former and the latter in age, admission serum creatinine and C3 levels, urinary protein excretion, or the frequency of renal tubular acidosis. Chronic azotemia developed in 3 and acute renal shutdown in another 2. Of 22 patients with sickle glomerulopathy (our 9 added to 13 from the literature) 11 died within 2 years. Ten of these (91 %) had developed renal failure, compared to only 5 of the 11 (45%) who survived longer than 2 years (p < 0.05). The 5-year mortality in the general population of sickle cell anemia is 3.75%, and 75% of patients aged 15 years or older survive 18 years or longer. The nephrotic syndrome, most often caused by sickle glomerulopathy, occurs in 4% of patients with sickle cell anemia, leading to renal failure in two-thirds and death in 2 years in half the patients. The development of chronic azotemia correlates strongly with early mortality. The prognosis is much worse than that in the general population of sickle cell anemia.
Carbamylated hemoglobin (carhb) is formed by the reaction of hemoglobin with cyanate, a product of in vivo urea dissociation. It is found in high levels in patients with renal failure and may be useful in their clinical evaluation. Accordingly, we measured carhb by HPLC after acid hydrolysis in 73 patients with renal failure and 11 controls. Mean carhb levels (expressed as micrograms valine hydantoin/g Hb), were highest in chronic renal failure (CRF, 146 +/- 13), intermediate in end-stage renal disease on hemodialysis (ESRD, 106 +/- 7), and lowest in acute renal failure (ARF, 80 +/- 12) when compared to normal subjects (27 +/- 2). In all patients carhb was significantly correlated with BUN but not with creatinine, bicarbonate, or phosphate. For any level of BUN above 80 mg/dl, carhb was substantially higher in CRF than in ARF. Predialysis BUN and urea reduction ratio (URR) were significant predictors of carhb in ESRD. To investigate the effect of time of exposure and BUN level on the rate of carbamylation of hemoglobin, blood from normal subjects and dialysis patients was incubated in vitro with urea equivalent to BUN levels of 50, 100, 150, and 200 mg/dl and assayed for carhb at 0, 5, 9, and 14 days. Carhb increased linearly over the first nine days of urea exposure and leveled off thereafter. The rate of carbamylation increased as BUN increased and was significantly higher in hemoglobin from dialysis patients than from normal subjects. These results show that the higher the level of carhb at baseline, the higher the rate of carbamylation upon exposure to increasing urea concentrations. We conclude that carhb formation is dependent on urea concentration and length of exposure to urea. The rate of carhb formation for a given urea concentration is greater in hemoglobin already carbamylated, and this may explain why carhb is higher in CRF than in ARF at BUN levels greater than 80 mg/dl. Carhb may thus be a useful index of the duration and degree of exposure to high blood urea levels in patients with renal failure, and may potentially serve as an index of the adequacy of dialysis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
334 Leonard St
Brooklyn, NY 11211
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.