Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Salmon calcitonin (SCT) is a well-tolerated peptide drug with a wide therapeutic margin and is administered parenterally for long-term treatments of bone diseases. Its clinical usefulness would be enhanced by the development of an orally active formulation. In this randomized crossover double-blinded phase I trial, controlled by both a placebo and a parenteral verum, we have tested a new oral formulation of SCT associated with a caprylic acid derivative as carrier. Eight healthy volunteers received single doses of 400, 800, and 1200 microg of SCT orally, a placebo, and a 10-microg (50 IU) SCT intravenous infusion. SCT was reliably absorbed from the oral formulation, with an absolute bioavailability of 0.5-1.4%, depending on the dose. It induced a marked, dose-dependent drop in blood and urine C-terminal telopeptide of type I collagen (CTX), a sensitive and specific bone resorption marker, with the effects of 1200 microg exceeding those of 10 microg intravenously. It also decreased blood calcium and phosphate, and increased the circulating levels of parathyroid hormone (PTH) and, transiently, the urinary excretion of calcium. It was well-tolerated, with some subjects presenting mild and transient nausea, abdominal cramps, diarrheic stools, and headaches. This study shows that oral delivery of SCT is feasible with reproducible absorption and systemic biological efficacy. Such an oral formulation could facilitate the use of SCT in the treatment of osteoporosis and other bone diseases.
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PMID:Bioavailability and biological efficacy of a new oral formulation of salmon calcitonin in healthy volunteers. 1216 2

A 36-yr-old woman began to suffer from headache, anorexia and general fatigue at 35 weeks' gestation. About 2 or 3 months after the delivery, fever, tachycardia and generalized musculoskeletal disorder appeared. Thereafter, they worsened rapidly, accompanied by a disturbance of consciousness and hypercalcemia. Thyrotoxicosis, due to a post-partum thyroiditis, and glucocorticoid deficiency, due to a pituitary failure, probably associated with lymphocytic hypophysitis, were also observed. All the symptoms and hypercalcemia disappeared after the glucocorticoid replacement therapy and the normalization of thyroid hormone levels. Serum and urinary bone resorption markers, such as urine pyridinoline (U-Pyr), urine deoxypyridinoline (U-DPD), urine amino-terminal telopeptide of type I collagen (U-NTx) and serum carboxy-terminal telopeptide of type I collagen (ICTP), were extremely high at the hypercalcemic state. In this case, they were 10 to 20 times higher than the normal upper limits, and then markedly decreased in a normocalcemic state, thereby showing an extreme acceleration of bone resorption in a state of both thyrotoxicosis and glucocorticoid deficiency.
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PMID:Elevated bone resorption markers in a patient with hypercalcemia associated with post-partum thyrotoxicosis and hypoadrenocorticism due to pituitary failure. 1563 35

This report describes a 38-year-old man with osteogenesis imperfecta who died of a ruptured cerebral artery aneurysm and bacterial meningitis. He had multiple long bone fractures in the past, and approximately 4 months before death, he had surgery to relieve symptoms of basilar impression. The surgery was complicated by a postoperative wound infection. For the next 4 months, he had intermittent headaches and vomiting. He was found dead in his bed at home. At autopsy, he had a ruptured anterior communicating artery aneurysm and bacterial meningitis. Cerebrospinal fluid and blood cultures had growth of Staphylococcus aureus. Osteogenesis imperfecta is a disorder of type I collagen. Type I collagen is present in many tissues, including blood vessels. The etiology of cerebral artery aneurysm formation is multifactorial. Some patients with cerebral artery aneurysms have been shown to have abnormalities in type III collagen. There has not been a reported relationship made between abnormalities in type I collagen and aneurysms. Meningitis can also result in cerebral artery aneurysms, but they are usually due to Aspergillus or Mycobacterium species. The case we report is unique; cerebral artery aneurysm formation may have been due to osteogenesis imperfecta and/or bacterial meningitis.
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PMID:Ruptured cerebral artery aneurysm and bacterial meningitis in a man with osteogenesis imperfecta. 1673 28

This randomized, double-blind, double-dummy, multicenter trial assessed safety and efficacy of a single dose of IV zoledronic acid (ZOL) 5 mg vs. oral alendronate (ALN) 70 mg weekly in postmenopausal women with low bone mineral density (BMD) who had previously been treated with ALN. Postmenopausal women who were receiving oral ALN for at least 1 year immediately prior to randomization and with lumbar spine or femoral neck BMD T-score values < or = -2.0 prior to initiation of ALN were randomized to one 15-min IV infusion of ZOL 5 mg plus 52 weeks of oral placebo (n=113) or one IV infusion of placebo plus 52 weeks of oral ALN 70 mg (n=112). End points included percent change in lumbar spine BMD from baseline to month 12 and relative change from baseline in urine N-telopeptide of type I collagen (NTX), serum C-telopeptide of type I collagen (CTX), amino terminal propeptides of type I collagen (PINP), and bone-specific alkaline phosphatase (bone ALP) over 12 months. Adverse events, bone histomorphometry and microscopic appearance, and patient preference for the 2 treatment regimens were also assessed. In this study, a single infusion of ZOL 5 mg maintained BMD 12 months following the switch from oral ALN in women with osteoporosis. The mean duration of prior ALN therapy at baseline was 4 years. Mean biomarker levels in the ALN 70-mg group remained at or close to baseline levels for the duration of the study. In the ZOL 5-mg group, mean biomarker levels were reduced from baseline after 3 months, returned to baseline after 6 months, and increased thereafter but remained within the premenopausal range. The overall rates of adverse events were comparable in the 2 groups (ZOL 5 mg, 86.7%; ALN 70 mg, 80.4%). Headache occurred more commonly within the first 3 days after infusion with ZOL 5 mg (12.4%) than with ALN 70 mg (6.3%). Bone biopsies indicate that both treatments decrease excessive remodeling seen in osteoporosis. The majority (78.7%) of patients expressed preference for once yearly infusion over weekly oral therapy. We conclude that patients can be switched from oral ALN to ZOL 5 mg infusion with maintenance of therapeutic effect for at least 12 months and that patients prefer a once yearly infusion to weekly oral therapy.
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PMID:Intravenous zoledronic acid 5 mg in the treatment of postmenopausal women with low bone density previously treated with alendronate. 1795 37

Osteoporosis is a widespread musculoskeletal deformity that affects thousands of older people every year, leading to bone abnormalities and ultimately increasing the risk of bone fractures in both genders. It is considered a lethal disease causing death in thousands of people at the late stage of life. Dendropanax morbifera Leveille is a subtropical broad-leaved prevalent species in Korea. Extracts of the leaves, stems, roots, and seeds of D. morbifera have been used in traditional medicine for the treatment of numerous diseases such as diabetes, atherogenesis, skin disorders, and headaches. However, the anti-osteoporosis effects of D. morbifera have not been examined. The primary objectives of this study were to elucidate the anti-osteoporosis effect of D. morbifera extract through an in vitro study using pre-osteoblastic MC3T3-E1 cells. We found that D. morbifera strongly increased the expression of bone metabolic markers such as alkaline phosphatase (ALP) activity, type I collagen (Col-I) level, and mineralization. Additionally, D. morbifera extract also upregulated the mRNA expression levels of osteogenic genes including ALP, osteocalcin (OCN), osterix (Osx), and runt-related transcription factor 2 (Runx2) in MC3T3-E1 cells via upregulation of bone morphogenetic protein 2 (BMP-2)/p38 MAPK/JNK and Smad1/5/8 signaling pathways. Moreover, addition of D. morbifera significantly suppressed the inhibitory effect of SB203580 (p38 inhibitor). In conclusion, the current study demonstrated that D. morbifera extract significantly increased osteoblast differentiation and mineralization in MC3T3-E1 cells by regulating BMP-2/p38/JNK and Smad1/5/8. Our study might be helpful in the discovery and development of new anti-osteoporosis therapeutic agents.
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PMID:In vitro evaluation of the potential therapeutic role of Dendropanax morbifera extract in ameliorating osteoporosis and resultant bone impairment using MC3T3-E1 cells. 2956 May 58