Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Heparinotherapy and systemic mastocytosis are two unusual aetiologies of diffuse osteopenia, possibly linked by common pathophysiological factors. Osteoporosis related to heparinotherapy has only been observed in patients treated with doses higher than 10,000 units per day and for more than 4 months. Even in these, it is a rare disorder which has only been reported approximately 15 times in the world literature. Bone histomorphometry has demonstrated the occurrence of marked hyperresorption. In vitro, heparin appears to have resorptive and collagenolytic effects which could play a pathophysiological part in the disorder. Diagnosis of the osteopenic form of systemic mastocytosis may be difficult. Urticaria pigmentosa is a very important clue but may be misdiagnosed or even missing. Hepato or splenomegaly are inconstant. X-rays may show the coexistence of osteosclerotic lesions. Standard biochemical tests are of little help. The urinary excretions of the histamine metabolites methyl histamine and methyl imidazolacetic acid have been found increased when measured. Finally, the diagnosis is made by bone histology which must be performed without decalcification and read by a pathologist informed of the potential diagnosis. Toluidine blue stain shows that mastocytes are numerous in the bone marrow where they are grouped in foci. Histomorphometry demonstrates a high bone turnover with excessive resorption, which could be mediated by heparin or PG E 2 contained in mastocyte granules. Treatment is difficult and may involve cytostatic drugs and/or inhibitors of bone resorption: Clodronate has recently been reported to be at least transiently effective.
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PMID:The osteoporosis of heparinotherapy and systemic mastocytosis. 266 67

A major constraint in the study of Plasmodium falciparum malaria, including vaccine development, lies on the parasite's strict human host specificity and therefore the shortage of animal experimental models able to harbor human plasmodia. The best experimental models are neo-tropical primates of the genus Saimiri and Aotus, but they require splenectomy to reduce innate defenses for achieving high and consistent parasitemias, an important limitation. Clodronate-liposomes (CL) have been successfully used to deplete monocytes/macrophages in several experimental models. We investigated whether a reduction in the numbers of phagocytic cells by CL would improve the development of P. falciparum parasitemia in non-splenectomized Saimiri sciureus monkeys. Depletion of S. sciureus splenocytes after in vitro incubation with CL was quantified using anti-CD14 antibodies and flow cytometry. Non-infected and P. falciparum-infected S. sciureus were injected intravenously twice a week with either CL at either 0.5 or 1 mL (5 mg/mL) or phosphate buffered saline (PBS). Animals were monitored during infection and treated with mefloquine. After treatment and euthanasia, spleen and liver were collected for histological analysis. In vitro CL depleted S. sciureus splenic monocyte/macrophage population in a dose- and time-dependent manner. In vivo, half of P. falciparum-infected S. sciureus treated with CL 0.5 mL, and two-thirds of those treated with CL 1 mL developed high parasitemias requiring mefloquine treatment, whereas all control animals were able to self-control parasitemia without the need for antimalarial treatment. CL-treated infected S. sciureus showed a marked decrease in the degree of splenomegaly despite higher parasitemias, compared to PBS-treated animals. Histological evidence of partial monocyte/macrophage depletion, decreased hemozoin phagocytosis and decreased iron recycling was observed in both the spleen and liver of CL-treated infected S. sciureus. CL is capable of promoting higher parasitemia in P. falciparum-infected S. sciureus, associated with evidence of partial macrophage depletion in the spleen and liver. Macrophage depletion by CL is therefore a practical and viable alternative to surgical splenectomy in this experimental model.
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PMID:Increased Plasmodium falciparum Parasitemia in Non-splenectomized Saimiri sciureus Monkeys Treated with Clodronate Liposomes. 2898 68