Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The major factor influencing scintigraphic detection of abnormal parathyroid glands seems to be their size. However, false-negative results have been reported in large glands while some very small adenomas have been identified. Other factors can influence 99mTc-MIBI and 99mTc-Tetrofosmin uptake and therefore the accurate detection of hyperfunctioning glands depends also on these. Increases in both perfusion and functional activity and targeting of abundant mitochondria-rich oxyphil cells seem to be relevant mechanisms of uptake. A relationship has been observed between the intensity of focal uptake in the parathyroid glands and the cell cycle phases for patients with secondary hyperparathyroidism. Higher uptake grades correlated with the active growing phase, showing that scintigraphy accurately reflects the functional status of the hyperplastic parathyroid glands. Serum calcium levels may modify radiotracer kinetics by influencing the membrane potential. In addition, P-glycoprotein or multidrug resistance (MDR) associated protein expression may play an important role in the false-negative results of parathyroid scintigraphy. If the lipophilic cationic radiotracers used in parathyroid scintigraphy are transported by the same mechanism as the anticancer drugs, they will be quickly eliminated from the parathyroid glands containing P-glycoprotein or MDR-related protein expression and the uptake in images will be negative. In parathyroid glands with no P-glycoprotein or MDR-related protein expression, the radiotracers remain in the cells, making it easier to detect them by scintigraphy.
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PMID:Biological factors influencing parathyroid localization. 1254 35

The surgical treatment of secondary hyperparathyroidism (HPTH) requires sub-total excision of parathyroid glands or total excision with their autotransplantation. Although this approach has been considered as a safe method of treatment, in this report we describe persisted/recurrent HPTH after parathyroid transplantation. Due to parathormone (PTH) hypersecretion and uncontrolled proliferation, the parathyroid grafts were removed and used for generation of cell cultures, which further have been subjected to in vitro studies. As a control we used parathyroid tissue, obtained during multiorgan harvesting. We found increased proliferation and up-regulated PTH production by the graft-derived, but not control in vitro cultured cells. Moreover, due to decrease of in vivo radiotracer uptake by parathyroid grafts, the expression of multi-drug resistance-involved factors, including P-glycoprotein (P-gp/mdr1), multi-drug resistance-associated protein (mrp) and bcl-2 have been investigated using RT-PCR. The analysis revealed increased expression of both, mdr1 and mrp in graft-derived cells, in contrast to control cells, which did not express P-gp/mdr1 or mrp. However, we did not observe any difference in expression of bcl-2 between analyzed cells. The up-regulated expression of P-gp/mdr1 on graft-derived cells was further confirmed by immunofluorescence studies. The described case indicates potential risk associated with transplantation of parathyroid tissue. Our results confirm a role of MDR phenomenon in occurrence of false negative results in parathyroid tissue scintigraphy studies. Moreover, they indicate that standard histological examination of transplanted material could not be sensitive enough to exclude any potential danger of abnormal graft progression. Thus, they could support the concept to use encapsulated parathyroid transplants.
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PMID:Persisted/recurrent hyperparathyroidism associated with development of multi-drug resistance phenotype and proliferation of parathyroid transplants. 1537 87

Precise localization of parathyroid glands using 99mTc-labeled hexakis-2-methoxyisobutylisonitrile (99mTc-MIBI) scintigraphy could be affected by various biological factors. There is increasing evidence that radiotracer retention could be controlled by members of multidrug resistance (MDR) system, especially P-glycoprotein (P-gp). Since the role of P-gp in tertiary hyperparathyroidism (T-HPTH) scintigraphic studies is poorly recognized, the aim of the study was to compare the correlation between parathyroid P-gp expression and results of their scintigraphy in T-HPTH versus primary hyperparathyroidism (P-HPTH). P-HPTH (n = 19) and T-HPTH (n = 18) patients were subjected to 99mTc-MIBI scintigraphy followed by surgical treatment. The parathyroid glands were assessed in routine hematoxylin-eosin staining and P-gp expression was analyzed using immunohistochemistry. Parathyroids collected during cadaver donor multi-organ harvesting were used as a control. It has been found that P-HPTH-derived parathyroid glands with predominating adenoma morphology expressed less P-gp, as compared to P-gp-rich T-HPTH glands, mainly displaying nodular or diffused hyperplasia phenotype. This finding reversely correlated with results of 99mTc-MIBI scintigraphy. However, we did not observe any difference in P-gp expression nor scintigraphy result between nodular or diffused hyperplasia. Altogether, these data suggest that P-gp overexpression in T-HPTH could be responsible for decreased sensitivity of 99mTc-MIBI scintigraphy in those patients. Therefore, the recently proposed reduced neck exploration or limited parathyroid resection on the basis of scintigraphy could create the risk of persisted/recurrent hyperparathyroidism. However, this problem requires further study.
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PMID:P-glycoprotein expression influences the result of 99mTc-MIBI scintigraphy in tertiary hyperparathyroidism. 1601 52

The parathyroid glands, which usually are situated behind the thyroid gland, secrete parathyroid hormone, or PTH, which helps maintain calcium homeostasis. Primary hyperparathyroidism results from excess parathyroid hormone secretion. In secondary hyperparathyroidism, the normal PTH effect on bone calcium release is lost. Serum PTH rises, causing generalized hyperplasia. In tertiary hyperparathyroidism, a complication of secondary hyperparathyroidism, normal feedback mechanisms governing PTH secretion are lost, parathyroid gland sensitivity to PTH decreases, and the threshold for inhibiting PTH secretion increases. 99mTc sestamibi, or MIBI, the current radionuclide study of choice for preoperative parathyroid localization, can be performed in various ways. The "single-isotope, double-phase technique" is based on the fact that MIBI washes out more rapidly from the thyroid than from abnormal parathyroid tissue. However, not all parathyroid lesions retain MIBI and not all thyroid tissue washes out quickly, and subtraction imaging is helpful. Many MIBI avid thyroid lesions also accumulate pertechnetate and iodine, and subtraction reduces false positives. Single-photon emission computed tomography provides information for localizing parathyroid lesions, differentiating thyroid from parathyroid lesions, and detecting and localizing ectopic parathyroid lesions. The most frequent cause of false-positive MIBI results is the solid thyroid nodule. Other causes include thyroid carcinoma, lymphoma, and lymphadenopathy. False-negative results occur because of several factors. Lesion size is important. Cellular function also may be important. Parathyroid tissue that expresses P-glycoprotein does not accumulate MIBI. Parathyroid adenomas that express either P-glycoprotein or the multidrug resistance related protein MRP are less likely to accumulate MIBI. MIBI scintigraphy is less sensitive for detecting hyperplastic parathyroid glands. In secondary hyperparathyroidism, MIBI uptake is more closely related to cell cycle than to gland size. Mitochondria-rich oxyphil cells presumably account for MIBI uptake in parathyroid lesions. Fewer oxyphil cells, and hence fewer mitochondria, may explain both lower uptake and rapid washout of MIBI from some lesions. MIBI is also less sensitive for detecting multigland disease than solitary gland disease.
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PMID:Radionuclide imaging of the parathyroid glands. 1615 Feb 47