Regeneration of kidney tubular epithelial cells

Conclusion The mechanisms that regulate regeneration of kidney epithelial cells after acute tubular necrosis are poorly understood. Repair of the nephron can take place in the adverse systemic metabolic setting caused by failure of renal function. This clinical observation suggests that factors released at the site of the tubular insult can mediate repair. Studies carried out in this and other laboratories show that kidney epithelial cells can release and respond to polypeptide growth factors which may thereby contribute to renal regeneration by autocrine and paracrine mechanisms. Specific growth factors secreted by cells and deposited in the tubular basement membrane prior to injury may subsequently participate in nephron repair. In addition, adenine nucleotides released from injured or dying cells at the injury site or provided exogenously could stimulate surviving renal epithelial cells at the edges of the wound to migrate along the basement membrane to rapidly reepithelialize the nephron and subsequently initiate mitogenesis to replace cells lost by necrosis.The nephrotoxic effect of many agents used in cancer chemotherapy and the older age of patients undergoing complicated surgical procedures has increased the incidence of ARF, whereas the mortality rate has not changed since the early 1950s [22]. Thus there is considerable need for innovative therapeutic strategies. An important goal of future research efforts is to identify new growth factors that facilitate migration, differentiation, and proliferation of renal epithelial cells at sites of tubular necrosis. Isolation and use of these agents in combination with dialysis and nutritional support could speed renal regeneration and thereby improve the outcome in patients with this condition.Abbreviations ARF acute renal failure - ECM extracellular matrix - EGF epidermal growth factor - FGF fibroblast growth factor - IGF insulin-like growth factor - MGSA melanocyte growth-stimulating activity - PDGF platelet-derived growth factor - IGF transforming growth factor     

Metastasising chordoma to the mandible from a rare vertebral site: the first reported case.

Chordoma is a rare tumor, arising from notochord remnants, which usually occurs in the axial skeleton and rarely metastasizes. Although there have been 3 previous reports of metastatic disease to the facial bones from sacrococcygeal chordoma, this is the first to describe spread to the mandible from a vertebral primary chordoma.     

A study of dose distribution patterns from cobalt-60 and Varian Clinac-4 beams.

Dose distribution patterns of 4 MV x-rays from a Varian Clinac 4 linear accelerator are compared with those from a 60Co teletherapy machine. Field flatteners of lead and depleted uranium were used. Dose distribution maps display the off-axis high dose or "horns" with lead filters and circular dose distribution patterns. The uranium field flattener clearly "clipped the horns" and eliminated circular dose distribution patterns with larger fields.     

MR findings in iatrogenic Gerbode defect

Congenital or acquired communication between left ventricle and right atrium is rare and can be easily overlooked as an eccentric tricuspid regurgitation jet. MRI is the ideal modality for accurate diagnosis, providing details for surgical planning about the location and size of the defect.     

Barriers to Effective Drug Treatment for Brain Metastases: A Multifactorial Problem in the Delivery of Precision Medicine

The treatment of metastatic lesions in the brain represents a serious unmet medical need in the field of neuro-oncology. Even though many effective compounds have demonstrated success in treating peripheral (non-CNS) tumors with targeted agents, one aspect of this lack of success in the brain may be related to poor delivery of otherwise effective compounds. Many factors can influence the brain delivery of these agents, but one key barrier is a heterogeneously “leaky” BBB that expresses efflux transporters that limit the BBB permeability for many targeted agents. Future success in therapeutics for brain metastases must take into account the adequate delivery of “active, free drug” to the target, and may include combinations of targeted drugs that are appropriate to address each individual patient’s tumor type. This review discusses some issues that are pertinent to precision medicine for brain metastases, using specific examples of tumor types that have a high incidence of brain metastases.     

Prevalence of Moderate or Severe Left Ventricular Diastolic Dysfunction in Persons With Suspected Myocardial Ischemia With and Without an Abnormal Adenosine or Exercise Sestamibi Stress Test or Coronary Revascularization

We investigated in 335 patients (mean age-63 year) with suspected myocardial ischemia the prevalence of moderate or severe left ventricular diastolic dysfunction (LVDD) in patients with an abnormal adenosine or exercise sestamibi stress test (SST) or prior coronary revascularization and in patients with a normal SST and no prior coronary revascularization. Moderate or severe LVDD was present in 117 of 142 patients (82%) with an abnormal SST or prior coronary revascularization and in 111 of 193 patients (58%) with a normal SST and no prior coronary revascularization (p < 0.001). Moderate or severe LVDD was present in 34 of 38 patients (89%) with an abnormal SST or prior coronary revascularization and an abnormal left ventricular ejection fraction (LVEF) and in 4 of 8 patients (50%) with a normal SST and no prior coronary revascularization and an abnormal LVEF (p < 0.01).     

Plasma Exchange for Hemolytic Crisis and Acute Liver Failure in Wilson Disease

Wilson disease (WD) is a rare autosomal recessive disorder of copper metabolism which primarily involves the liver and the central nervous system. Rarely, WD can present as acute liver failure (ALF) and this disease is universally fatal in the absence of liver transplantation. The authors report a young girl with WD ALF, who showed signs of recovery after prompt initiation of plasma exchange (PE) and chelation therapy. Though liver transplantation could not be done in this child and the child died 8 d after stopping PE, this case highlights that PE can be a successful medical treatment in WD ALF and should be considered as a therapeutic measure to stabilize a patient by decreasing serum copper, reducing hemolysis, and helping to prevent renal tubular injury from copper and copper complexes until liver transplantation is possible.     

Characterization of Extracellular Signal-Regulated Kinase 5 Levels in Human Umbilical Vein Endothelial Cells Exposed to Disturbed and Uniform Flow

Extracellular signal-regulated kinase 5 (ERK5) has been reported to regulate endothelial cell integrity and protect from vascular dysfunction under continuous laminar flow. However, the effect of flow on ERK5 levels has not been determined. Confluent human umbilical vein endothelial cells (HUVECs) were seeded on fibronectin coated glass slides and serum starved for 2 hours with 1% fetal bovine serum (FBS). HUVECs were then exposed to to and fro flow (TFF), pulsatile forward flow (PFF), or continuous laminar flow (CLF) in a parallel plate flow chamber for up to 2 hours. At the end of experiment, cell lysates were prepared and immunoblotted with antibodies to total ERK5. Both CLF and TFF exhibited a decrease in ERK5 after levels after 2-hour exposure. However, the level of ERK5 for PFF remained the same. Disturbed, but not uniform pulsatile, flow decreases ERK5 levels in HUVECs.