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Samuel N Heyman

Publications and source records attributed to Samuel N Heyman.

24 records · Page 2Linked to original sources
PubMed2003

Effect of poly(ADP-ribose) polymerase inhibition on outer medullary hypoxic damage.

Poly(ADP-ribose) polymerase (PARP) activation after free-radical-induced DNA damage depletes cellular energy stores and participates in ischemia-reflow injury. We studied the potential protective effect of the water-soluble PARP inhibitor 3-aminobenzamide (3-AB) in a rat model of acute renal failure (ARF) from combined administration of radiocontrast, indomethacin and N(omega)-nitro-L-arginine methyl ester. Kidney function at 24 h was better preserved in rats treated with 3-AB as compared to control animals. However, the extent of tubular hypoxic damage was not significantly mitigated. It is concluded that PARP inhibition may attenuate renal dysfunction in this model of ARF with medullary hypoxic tubular injury even while the extent of tubular necrosis is not significantly altered. Further studies of this dyssynchrony of structure and function may provide important insights into the sequence of events that promotes renal failure after medullary injury.

Acute Kidney Injury↗
PubMed2002

Autoimmune cholangiopathy associated with systemic lupus erythematosus.

We report a 39-year-old female who presented over 11 years with autoimmune cholangiopathy associated with kaleidoscopic manifestations of systemic lupus erythematosus (SLE), including, arthritis, skin changes, pleuritis, diffuse proliferative glomerulonephritis, lymphadenopathy, splenomegaly, hyperglobulinemia, and major depression. While antimitochondrial antibodies (AMA) were absent, antinuclear (ANA) and anti-DNA antibodies were detected in high titres associated with hypocomplementemia. The patient also had vitamin B12 deficiency and antiphospholipid antibodies. The patient required steroids and repeated courses of cyclophosphamide for the management of lupus nephritis, and ursodeoxycholic acid (ursolite) administration resulted in amelioration of cholestatic laboratory abnormalities. This unusual case report and review of literature illustrate that immune liver disease may be an important clinical manifestation of SLE, especially autoimmune cholangiopathy.

Adult↗
PubMed2002

Animal models of acute tubular necrosis.

The evaluation and management of acute renal failure in the ICU patient remains a formidable task because of the complexity of this condition. Clinical and physiologic assessment and complementing laboratory and imaging tests are currently insufficient to differ between true renal parenchymal damage (acute tubular necrosis; it is important to realize that this term does not necessarily imply widespread injury, because whole organ dysfunction in humans has often been associated with very limited parenchymal cellular necrosis) and prerenal azotemia (decreased renal blood flow with altered glomerular hemodynamics and subsequently diminished glomerular filtration, without significant epithelial cell injury). Moreover, tubular damage and altered glomerular hemodynamics may coexist or lead to each other, and their relative contribution to the evolving renal dysfunction has not been unequivocally established. The limited data regarding the renal pathology of such patients and the scant information about human morphologic and functional correlates further undermine our knowledge about diagnostic and therapeutic approaches to these patients. Advanced techniques are critically needed to establish noninvasively the dynamic status of renal parenchymal microcirculation and the distribution of intrarenal oxygenation and to identify evolving cellular energy depletion and tubular cell damage. A few technologies are potentially promising, such as blood oxygen level dependent magnetic resonance imaging, positron emission tomography, and kidney injury molecule-1 detection in patients' urine. Because of the difficulties in analyzing the pathophysiology in humans, clinicians continue to rely largely on animal models to guide understanding and rationale for the identification of therapeutic targets. Data from such animal studies are complemented by studies in isolated perfused kidneys, isolated tubules, and tubular epithelial cell cultures. In this report, we summarize some concepts of acute tubular necrosis that have evolved as a result of these studies, evaluate available animal models, and underscore controversies regarding experimental acute tubular necrosis.

Animals↗
PubMed2002

Proximal tubular injury attenuates outer medullary hypoxic damage: studies in perfused rat kidneys.

The straight segment (S3) of the proximal tubule is predominantly damaged during renal ischemia-reflow, whereas medullary thick ascending limbs (mTALs) are principally affected in other models of hypoxic acute tubular necrosis (ATN). Since the latter injury pattern largely depends on the extent of reabsorptive activity during hypoxic stress, we hypothesized that proximal tubular damage might attenuate downstream mTAL injury by means of diminished distal solute delivery for reabsorption. In isolated rat kidneys perfused for 90 min with oxygenated Krebs-Henseleit solution, mTAL necrosis developed in 75 +/- 3% of tubules in the mid-inner stripe of the outer medulla. By contrast, S3 segments in the outer stripe were minimally affected, with tubular fragmentation involving some 5 +/- 2% of tubules. In kidneys subjected in vivo to proximal tubular injury and subsequently used for isolated perfusion studies, the injury pattern was inverted: following 20 and 30 min ischemia and reflow for 24 h, S3 fragmentation rose to 18 +/- 16% and 72 +/- 13%, while mTAL damage was reduced to 33 +/- 10 and 24 +/- 8%, respectively. In kidneys subjected in vivo to D-serine S3 necrosis rose to 100%, while mTAL damage fell to 1 +/- 1% (p < 0.001). Substantial S3 tubular collapse (involving approximately 30% of tubules) and inner stripe interstitial hemorrhage were also noted, exclusively in kidneys subjected to ischemia-reflow. Proximal tubular necrosis alone or in combination with collapse inversely correlated with mTAL necrosis (R = -0.51 and -0.72, respectively, p < 0.003). This cogent inverse association might imply that disruption of the proximal nephron attenuates downstream mTAL necrosis by a reduction of distal tubular reabsorptive workload.

Animals↗