hypercalcemia/protease

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Design of potent, selective, and orally bioavailable inhibitors of cysteine protease cathepsin k.

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Osteoclast-mediated bone matrix resorption has been attributed to cathepsin K, a cysteine protease of the papain family that is abundantly and selectively expressed in osteoclast. Inhibition of cathepsin K could potentially be an effective method to prevent osteoporosis. Structure-activity studies

Role of Parathyroid Hormone Related Peptide (PTHrP) in Hypercalcemia of Malignancy and the Development of Osteolytic Metastases.

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Hypercalcemia of malignancy carries an extremely grim prognosis. The most common mechanism underlying hypercalcemia of malignancy is production by the tumor cells of cytokines responsible for osteoclastic differentiation and, therefore, lysis of the bone adjacent to the tumor. A minority of cases

Hypercalcemia causes acute pancreatitis by pancreatic secretory block, intracellular zymogen accumulation, and acinar cell injury.

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BACKGROUND Because hypercalcemia is a known etiologic factor for human acute pancreatitis, studies of the pancreatic pathophysiology and pathomorphology of experimental hypercalcemia have potential clinical significance. METHODS Rats received central venous infusion of either 0.6 mmol/kg per hour

Acute hypercalcemia causes acute pancreatitis and ectopic trypsinogen activation in the rat.

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OBJECTIVE Clinical and experimental observations have associated acute and chronic hypercalcemia with pancreatitis. The aim of this study was to determine whether acute hypercalcemia can induce acute pancreatitis and, if so, whether the pathogenesis involves premature protease

Modified immunoradiometric assay of parathyroid hormone-related protein: clinical application in the differential diagnosis of hypercalcemia.

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We have developed a sensitive, specific solid-phase immunoradiometric assay (IRMA) of parathyroid hormone-related protein (PTH-RP) with use of affinity-purified polyclonal immunoglobulins. Antibodies recognizing PTH-RP(37-74) are immobilized to a polystyrene bead to "capture" analytes from the

Ileal Tuberculosis Causing Hypercalcemia and Renal Failure.

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Hypercalcemia rarely causes acute pancreatitis due to secretory block in the pancreas and damage by accumulated proteases. Hypercalcemia, though described in granulomatous disorders, is uncommon in tuberculosis. Acute kidney injury is known to occur with acute pancreatitis, secondary to sepsis and

Immune reconstitution associated hypercalcemia.

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The emergence of highly active antiretroviral therapy using combinations of reverse transcriptase and protease inhibitors ushered the dawn of a new era in management of human immunodeficiency virus infection. Immune reconstitution inflammatory syndrome is an adverse consequence of the restoration of

Characterization of canine renal receptors for the parathyroid hormone-like protein associated with humoral hypercalcemia of malignancy.

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Parathyroid hormone-like proteins (PTHLP) display actions in the kidney which are similar to those of parathyroid hormone (PTH). We compared the binding properties of PTHLP and PTH in canine renal cortical membranes to determine if they interacted with the same or different receptors.

Specificity and stability of a new PTH1 receptor antagonist, mouse TIP(7-39).

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Parathyroid hormone 1 (PTH1) receptor antagonists might be of benefit in hypercalcemia of malignancy (HHM) and hyperparathyroidism. We previously identified bovine tuberoinfundibular peptide (7-39) (bTIP(7-39)) as a high-affinity PTH1 receptor antagonist. Mouse TIP(7-39) is an antagonist (rPTH1

Proparathyroid hormone-related protein is associated with the chaperone protein BiP and undergoes proteasome-mediated degradation.

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Parathyroid hormone-related peptide (PTHrP) is an important causal factor for hypercalcemia associated with malignancy. In addition to the endocrine functions attributed to secretory forms of the peptide, PTHrP also plays a local role as a mediator of cellular growth and differentiation presumably

Structure-based design of specific cathepsin inhibitors and their application to protection of bone metastases of cancer cells.

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We report the antihypercalcemic and antimetastatic effects of CLIK-148 in vivo, which is a specific inhibitor of cathepsin L. The decalcification during bone absorption is followed by the degradation of type-1 collagen by osteoclastic cathepsins. Tumor-bearing osteoclasts or TNF-alpha-activated

Cinacalcet sustainedly prevents pancreatitis in a child with a compound heterozygous SPINK1/AP2S1 mutation.

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Familial hypocalciuric hypercalcemia is an autosomal dominant genetic disorder characterized by hypercalcemia associated with inappropriate hypocalciuria and normal parathyroid hormone levels. Acute recurrent pancreatitis (ARP) is rare in children. Predisposing factors include hypercalcemia and

Modification of the analysis of parathyroid hormone-related protein in milk and concentrations of this protein in commercial milk and milk products in Japan.

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Parathyroid hormone-related protein (PTHrP), which causes hypercalcemia associated with malignant tumors, is known to be present in milk. Gene expression of PTHrP in the mammary gland increases markedly during parturition and with the onset of lactation. Even when circulating PTHrP levels are

Pancreatitis risk in primary hyperparathyroidism: relation to mutations in the SPINK1 trypsin inhibitor (N34S) and the cystic fibrosis gene.

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OBJECTIVE Primary hyperparathyroidism (pHPT)-related hypercalcemia is considered to represent a risk factor for the development of pancreatitis. We therefore explored whether mutations in genes that were previously identified to increase the risk for pancreatitis coexist in a cohort of 826 patients

Avascular Necrosis of Both Hips From Iatrogenic Cushing 's Syndrome due to Coadministration of Fluticasone and Ritonavir in an HIV-Infected Patient

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We report a case of avascular necrosis (AVN), hypercalcemia, and iatrogenic Cushing's syndrome in an HIV-positive patient taking inhaled (ICS) and nasal corticosteroids fluticasone and ritonavir. A 45-year-old HIV-infected African-American woman was seen for initial evaluation for multinodular

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