Biomedical subjects

P Shanley

Publications and source records attributed to P Shanley.

5 recordsLinked to original sources

PubMed1994

Ethnopharmacology in the Brazilian Amazon.

The potential pharmaceutical wealth of the Brazilian Amazon has attracted international attention from the general and scientific community. The role that ethnopharmacology can have in the discovery and development of new drugs from a region hosting such enormous cultural and biological diversity is discussed. A review is given of ethnopharmacological and ethnobotanical studies that have been conducted in the Brazilian Amazon over the past twenty years.

Brazil↗

PubMed1990

Effects of lithium on cAMP generation in cultured rat inner medullary collecting tubule cells.

The effects of lithium (Li) on the cAMP system in rat inner medullary collecting tubule cells were studied. While acute exposure to 5 mM Li was without effect, 10 mM, 25 mM and 50 mM Li significantly decreased AVP-stimulated cAMP formation. In contrast, cells grown in 5 mM Li for 72 hours which caused no morphologic changes enhanced cAMP formation (fmol/microgram protein) in response to both 10 nM AVP (114.5 +/- 9.2 vs. 71.6 +/- 7.4, P less than 0.005) and 100 nM AVP (182 +/- 14 vs. 120 +/- 8.3, P less than 0.001), N = 16. A similar enhancement was observed when cAMP formation was stimulated by a post-receptor agonist, cholera toxin. The role of eicosanoids was examined with 5 microM meclofenamate which reversed Li-enhanced cAMP formation in response to both AVP and cholera toxin. To define the eicosanoid responsible, cyclooxygenase products were measured. Prostaglandin E2 and thromboxane B2 synthesis were unchanged by Li, but the production of prostacyclin was significantly (P less than 0.02) increased. Prostacyclin (3 microM) mimicked the effect of Li to enhance the response to 10 nM AVP as cAMP levels increased from 100 +/- 11 to 173 +/- 13, P less than 0.05. The experiments suggest that acute exposure of Li at concentrations of 10 mM or greater inhibit cAMP formation but prolonged Li exposure enhances cAMP formation by increasing the formation of prostacyclin.

Animals↗

PubMed1986

Progressive tubulointerstitial renal disease in infancy with associated hepatic abnormalities.

Clinical, pathologic, and biochemical data are reported in two male infants who had rapidly progressive renal failure, enlarged kidneys, hepatosplenomegaly, and fat malabsorption. One infant, studied prior to the onset of significant renal insufficiency, manifested renal Fanconi syndrome, hyperparathyroidism, and marked hypocalcemia. After a brief period of dialysis, both received renal transplants. Neither has clinical evidence of reoccurrence of the renal disorder in the transplant, but both still have hepatic abnormalities. Morphologic features present in both patients include a renal lesion characterized by tubulointerstitial injury with a tubulocystic component and hepatic abnormalities with bile duct proliferation, portal fibrosis, and inflammation. These cases do not readily conform to any single published diagnostic category, including nephronophthisis-congenital hepatic fibrosis or infantile polycystic kidney disease, and appear to be unique.

Biopsy↗

PubMed1986

Renal response to shock.

Renal hypoperfusion such as occurs in shock creates an environment in which cellular injury and organ dysfunction can occur during the episode of shock as well as during reoxygenation and reperfusion. A severe decrement in oxygen delivery compromises energy (adenosine triphosphate) production, leading to various degrees of cell injury ranging from cell swelling to acute cortical necrosis. These different responses of the kidney to shock explain the multiple clinical presentations varying from an isolated loss of concentrating ability to prolonged anuria. Many cellular events contribute to renal cell injury, including cellular ATP depletion, cellular and mitochondrial calcium overload, and activation of phospholipases and oxygen radical formation. Recent clinical and experimental studies suggest that ATP-MgCl2, free radical scavengers, diuretics, vasodilators, and calcium channel blockers appear to be beneficial in preventing acute tubular necrosis after anoxic or severe hypoxic insults. Thus these agents may be helpful in altering the course of acute renal failure in shock patients and may decrease their morbidity and mortality.

Acute Kidney Injury↗

PubMed1985

Disparate mechanisms for hypoxic cell injury in different nephron segments. Studies in the isolated perfused rat kidney.

Hypoxic injury was evaluated morphologically in the proximal tubule and in the medullary thick ascending limb of isolated rat kidneys perfused for 90 min without O2 or with various metabolic inhibitors. Inhibition of mitochondrial respiration (with rotenone, antimycin, oligomycin) or of intermediary metabolism (with monofluoroacetate, malonate, 2-deoxyglucose) caused reduction in renal oxygen consumption, renal function, and ATP content comparable with those elicited by oxygen deprivation. Metabolic inhibition produced hypoxiclike injury in the first portions of the proximal tubule, S1 and S2 ("clubbing" of microvilli, mitochondrial swelling), and the extent of damage was correlated with the degree of ATP depletion. In the third portion of the proximal tubule, S3, hypoxiclike damage (cytoplasmic edema or fragmentation) occurred most consistently when both aerobic and anaerobic metabolism were inhibited simultaneously. In the medullary thick ascending limb, none of the metabolic or mitochondrial inhibitors used could reproduce the injury of oxygen deprivation. Thus, the proximal tubule and the thick ascending limb have markedly different responses to cellular energy depletion, suggesting disparate mechanisms for hypoxic injury along the nephron.

Adenosine Triphosphate↗