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P Justo

Publications and source records attributed to P Justo.

11 recordsLinked to original sources
PubMed2006

Cytokine cooperation in renal tubular cell injury: the role of TWEAK.

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK, TNFSF12) is a member of the TNF superfamily. TWEAK activates the Fn14 receptor, and may regulate apoptosis, proliferation, and inflammation, processes that play a significant role in pathological conditions. However, there is little information on the function and regulation of this system in the kidney. Therefore, TWEAK and Fn14 expression were studied in cultured murine tubular epithelial MCT cells and in mice in vivo. The effect of TWEAK on cell death was determined. We found that TWEAK and Fn14 expression was increased in experimental acute renal failure induced by folic acid. Cultured tubular cells express both TWEAK and the Fn14 receptor. TWEAK did not induce cell death in non-stimulated tubular cells. However, in cells costimulated with TNFalpha/interferon-gamma, TWEAK induced apoptosis through the activation of the Fn14 receptor. Apoptosis was associated with activation of caspase-8, caspase-9, and caspase-3, Bid cleavage, and evidence of mitochondrial injury. There was no evidence of endoplasmic reticulum stress. A pan-caspase inhibitor benzyloxycarbonyl-Val-Ala-DL-Asp prevented TWEAK-induced apoptosis, but it sensitized cells to necrosis via generation of reactive oxygen species. In conclusion, cooperation between inflammatory cytokines results in tubular cell death. TWEAK and Fn14 may play a role in renal tubular cell injury.

Acute Kidney Injury↗
PubMed2006

Lethal activity of FADD death domain in renal tubular epithelial cells.

Fas-associated death domain (FADD) is an adaptor protein that is required for the transmission of the death signal from lethal receptors of the tumor necrosis factor superfamily. FADD contains a death domain (DD) and a death effector domain (DED). As death receptors contribute to renal tubular injury and tubular cell FADD increases in acute renal failure, we have studied the function of FADD in tubular epithelium. FADD expression was studied in kidney samples from mice. In order to study the contribution of FADD to renal tubular cell survival, FADD or FADD-DD were overexpressed in murine tubular epithelium. FADD is expressed in renal tubules of the healthy kidney. Both FADD and FADD-DD induce apoptosis in primary cultures of murine tubular epithelium and in the murine cortical tubular cell line. Death induced by FADD-DD has apoptotic morphology, but differs from death receptor-induced apoptosis in that it is not blocked by inhibitors of caspases. Neither an inhibitor of serine proteases nor overexpression of antiapoptotic BclxL prevented cell death. However, the combination of caspase and serine protease inhibition was protective. FADD and FADD-DD overexpression decreased nuclear factor kappa B activity. These data suggest that FADD has a death regulatory function in renal tubular cells that is independent of death receptors. FADD-DD is sufficient to induce apoptosis in these cells. This information is relevant to understanding the role of FADD in tubular injury.

Acute Kidney Injury↗
PubMed2006

Modulation of renal tubular cell survival: where is the evidence?

Tubular cell loss is prominent both in acute and chronic renal failure. Apoptosis and its regulatory mechanisms contribute to cell number regulation in the kidney. The potential role of apoptosis ranges from induction and progression to repair of renal injury. However, therapeutic interest has focused in preventing the apoptotic loss of tubular cells that leads to acute and chronic renal failure. Death ligands and receptors, such as tumor necrosis factor and Fas ligand, proapoptotic and antiapoptotic Bcl2 family members and caspases have all been shown to participate in apoptosis regulation in the course of renal cell injury. Nevertheless, the precise role of these proteins is unclear, and the participation of most known apoptosis regulatory proteins has not been studied. We now review the role of apoptosis in renal injury, the potential molecular targets of therapeutic intervention, the therapeutic weapons to modulate the activity of these targets and the few examples of therapeutic intervention on apoptosis, with emphasis in acute renal failure.

Acute Kidney Injury↗
PubMed2002

Apoptotic cell death in renal injury: the rationale for intervention.

Cell number abnormalities are frequent in renal diseases, and range from the hypercellularity of postinfectious glomerulonephritis to the cell depletion of chronic renal atrophy. Recent research has shown that apoptosis and its regulatory mechanisms contribute to cell number regulation in the kidney. The potential role of apoptosis ranges from induction and progression to repair of renal injury. Death ligands and receptors, such as tumor necrosis factor and Fas ligand, proapoptotic and antiapoptotic Bcl2 family members and caspases have all been shown to participate in apoptosis regulation in the course of renal cell injury. However, the precise role of these proteins is unclear, and the participation of most known apoptosis regulatory proteins has not been studied. We now review the role of apoptosis in renal injury, the potential molecular targets of therapeutic intervention, the therapeutic weapons to modulate the activity of these targets and the few examples of therapeutic intervention on apoptosis, with emphasis on the acute tubular necrosis.

Animals↗
PubMed2000

Role and regulation of apoptotic cell death in the kidney. Y2K update.

Apoptosis is an active form of cell death that, in balance with mitosis, regulates cell number. Cell number abnormalities are a frequent feature of renal disease. We now review current concepts on the molecular regulation of apoptotic cell death, including the influence of survival and lethal factors from the extracellular microenvironment as well as the role of intracellular regulators of apoptosis, such as death receptors, proapoptotic and antiapoptotic bcl2-related proteins, the mitochondria and caspases. In addition the role of apoptosis in the genesis, persistence and progression and remodeling and resolution of renal injury is discussed. Information on the expression and function of apoptosis regulatory proteins in specific renal syndromes is summarized. Finally, future perspectives in research and clinical intervention are discussed.

Apoptosis↗
PubMedDate not supplied

Contribution of apoptotic cell death to renal injury.

Cell number abnormalities are frequent in renal diseases, and range from the hypercellularity of postinfectious glomerulonephritis to the cell depletion of chronic renal atrophy. Recent research has shown that apoptosis and its regulatory mechanisms contribute to cell number regulation in the kidney. The role of apoptosis ranges from induction to repair and progression of renal injury. Death ligands and receptors, such as TNF and FasL, proapoptotic and antiapoptotic Bcl-2 family members and caspases have all been shown to participate in apoptosis regulation in the course of renal injury. These proteins represent potential therapeutic targets, which should be further explored.

Animals↗
PubMedDate not supplied

[Tetanus in a drug addict and HIV carrier patient].

We report the resuscitation of a woman with a severe tetanic process, dependence on drugs and acquired immunodeficiency syndrome. During her course, the patient presented high hemodynamic lability and supraventricular and ventricular ectopic beats. Impairment of oxygenation and ventilation led to tracheotomy and controlled ventilation for 25 days. Then, intermittent mandatory ventilation was initiated and maintained for 15 days. The patient was extubated. Partial pressure of oxygen in the arterial blood was 73 mmHg and PaO2/FIO2 was 183; she had a sepsis of pulmonary origin. High doses of sedative and analgesic agents (diazepam, 40 mg/hour and morphine, 2.5 mg/hour) were required. We believe the acme of the process was on days 13 and 15 during her stay at the resuscitation unit. We conclude that neither the symptomatology nor her course nor the treatment differed from other severe forms of tetanus treated by us. The infective process did not fit into what would be expected in an immunodeficient background.

Adult↗
PubMedDate not supplied

[A case of malignant hyperthermia: anesthesia and recovery].

We report the case of a 29-years-old woman with Menière's syndrome undergoing surgery to drain the endolymphatic sack. After anesthetic induction trismus developed but tubes were inserted without difficulty. Tachycardia began 15 min after start of balanced anesthesia with isoflurane, as arterial oxygen saturation and CO2 pressure decreased and temperature increased. These symptoms responded favorably to immediate treatment with dantrolene sodium, which was continued for 30 h in the ward for postoperative intensive care. Blood chemistry reports showed high enzyme levels that peaked at 24 h. We stress the importance of monitoring end tidal CO2 pressure and of rapidly starting specific treatment with dantrolene for correction of the clinical picture described.

Adult↗
PubMedDate not supplied

[Phreno-mediastinal hydatidosis and cysto-aortic fistula with multiple systemic embolism].

We present a 52-year-old patient who came to the emergency room with non-specific symptoms and whose clinical profile after 24 hours included acute abdomen and paresthesia in both lower extremities. A chest film revealed mediastinic enlargement; embolism was suspected. During surgery intestinal ischemia was found in the superior mesenteric artery; this was resected and termino-terminal anastomosis was accomplished with the remaining jejunum and the descending colon. At the same time, some flaccid vesicles were removed along with embolis in the femoral arteries, leading to suspicion of hydatid embolism. Transthoracic and transesophageal echocardiography showed multivessicular masses with internal blood flow in the posterior-inferior mediastinum, suggestive a ruptured hydatid cyst in the thoracic aorta. This was confirmed by thoracic-abdominal computed tomography. The patient's condition worsened, with acute renal failure, ischemia, necrosis of both legs and multiorgan failure leading to death. We discuss the rarity of this case, the use of imaging tools for diagnosis, and the inexorability of the disease in spite of treatment.

Abdomen, Acute↗