INT6625

Context Info Confidence 0.58 First Reported 1981 Last Reported 2010 Negated 4 Speculated 2 Reported most in Body Documents 96 Total Number 98 Disease Relevance 57.60 Pain Relevance 8.24

extracellular space (Pth) extracellular region (Pth) cellular_component (Pth)

Anatomy Link Frequency parathyroid 38 osteoclast 4 plasma 3 capsules 2 Kidney 2 Pth (Rattus norvegicus)

Pain Link Frequency Relevance Heat Pain 141 100.00 pruritus 37 100.00 monoamine 2 100.00 opiate 1 100.00 peptic ulcer disease 1 99.70 Action potential 7 99.16 spinal inflammation 5 99.00 lidocaine 3 98.76 Regional anesthesia 1 97.68 anesthesia 30 96.36

Disease Link Frequency Relevance Heat Pain 105 100.00 Uremia 76 100.00 Pruritus 69 100.00 Hypotension 4 99.98 Osteoporotic Fractures 26 99.96 Hypercalcemia 900 99.82 Hyperplasia 199 99.72 Disease 116 99.70 Sarcoidosis 27 99.60 Ulcers 5 99.54

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

In addition they can result in over-suppression of parathyroid hormone (PTH), adynamic bone, and are associated with both soft tissue and vascular calcification (Goodman et al 2000; Goodman 2001).

Negative_regulation (suppression) of PTH in parathyroid associated with calcification

1) Confidence 0.58 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2621404 Disease Relevance 0.56 Pain Relevance 0

In addition they can result in over-suppression of parathyroid hormone (PTH), adynamic bone, and are associated with both soft tissue and vascular calcification (Goodman et al 2000; Goodman 2001).

Negative_regulation (suppression) of parathyroid hormone in parathyroid associated with calcification

2) Confidence 0.58 Published 2008 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC2621404 Disease Relevance 0.56 Pain Relevance 0

The other aminopyridine 2A-7 (3 X 10(-5) - 3 X 10(-4) M) caused suppression of the compound action potential, a diminished propagation velocity and a reduction of the PTH, an action also observed with lidocaine.

Negative_regulation (reduction) of PTH associated with action potential and lidocaine

3) Confidence 0.57 Published 1987 Journal Eur. J. Pharmacol. Section Abstract Doc Link 3691629 Disease Relevance 0 Pain Relevance 0.42

Patients in the exemestane group had a significant decrease in BMD and early parathyroid hormone (at month 6) and an increase in bone alkaline phosphatase (B-ALP) and the carboxy-terminal telopeptide of type I collagen after 24 months.

Negative_regulation (decrease) of parathyroid hormone in parathyroid

4) Confidence 0.57 Published 2007 Journal Breast Cancer Res Treat Section Body Doc Link PMC2001222 Disease Relevance 0.30 Pain Relevance 0

Treatment reduced inappropriately elevated parathyroid hormone levels, presumably caused by long-term bisphosphonate use.

Negative_regulation (reduced) of parathyroid hormone in parathyroid

5) Confidence 0.56 Published 2010 Journal Cancer Section Body Doc Link 19918922 Disease Relevance 0.12 Pain Relevance 0

A small but statistically significant increase in serum calcium was seen, as was a significant decrease in serum parathyroid hormone.

Negative_regulation (decrease) of parathyroid hormone in parathyroid

6) Confidence 0.56 Published 2010 Journal Cancer Section Body Doc Link 19918922 Disease Relevance 0.14 Pain Relevance 0

Systemic factors such as oestrogen deprivation and parathyroid hormone strongly activate remodelling and can, in several circumstances, lead to imbalances in the remodelling cycle.

Negative_regulation (deprivation) of parathyroid hormone in parathyroid

7) Confidence 0.56 Published 2000 Journal Baillieres Best Pract Res Clin Endocrinol Metab Section Abstract Doc Link 11035901 Disease Relevance 0.34 Pain Relevance 0.07

Treatment with a new calcimimetic agent, cinacalcet HCl (Mimpara, Amgen, Munich, Germany), resulted in a rapid decline in elevated parathyroid hormone levels, near normalization of other laboratory markers of bone metabolism, improvement in mobility and skeletal pain caused by renal osteodystrophy, and an increase in body weight.

Negative_regulation (decline) of parathyroid hormone in parathyroid associated with pain, renal osteodystrophy and body weight

8) Confidence 0.56 Published 2008 Journal J Ren Nutr Section Abstract Doc Link 18558304 Disease Relevance 0.61 Pain Relevance 0.10

Although immunotherapy produced a partial response, it failed to decrease serum parathyroid hormone to the levels recommended by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative clinical practice guidelines.

Neg (failed) Negative_regulation (decrease) of parathyroid hormone in Kidney associated with renal disease

9) Confidence 0.56 Published 2008 Journal J Ren Nutr Section Abstract Doc Link 18558304 Disease Relevance 0.36 Pain Relevance 0.07

Like calcitriol, paricalcitol suppresses pre-pro-PTH mRNA synthesis and has a prolonged effect of PTH inhibition beyond its mean half-life of approximately 14 hours in hemodialysis patients (Cato et al 1998; Brandi et al 2002; Staniforth et al 2005).

Negative_regulation (inhibition) of PTH

10) Confidence 0.55 Published 2006 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1936265 Disease Relevance 0.17 Pain Relevance 0

Randomized trials have been conducted showing that paricalcitol capsules demonstrate effective suppression of PTH, achieving ?

Negative_regulation (suppression) of PTH in capsules

11) Confidence 0.55 Published 2006 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1936265 Disease Relevance 0.49 Pain Relevance 0

Indirect comparison of these results suggests paricalcitol effectively suppressed PTH with smaller alterations in serum calcium and phosphorus.

Negative_regulation (suppressed) of PTH

12) Confidence 0.55 Published 2006 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1936265 Disease Relevance 0.77 Pain Relevance 0

A study in CKD patients showed that oral calcitriol suppressed baseline PTH levels by 25% over 1 year of treatment, but at doses between 0.25 mcg/day and 1 mcg/day, calcitriol led to hypercalcemia in 64% of patients in the trial and a 139% increase in urinary calcium excretion after 1 year (Calcitriol new drug application [NDA] 18-044 FDA).

Negative_regulation (suppressed) of PTH associated with chronic renal failure and hypercalcemia

13) Confidence 0.55 Published 2006 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1936265 Disease Relevance 0.61 Pain Relevance 0

In comparison, paricalcitol capsules had a mean PTH suppression of 42% with only 2% of patients in the paricalcitol groups experiencing hypercalcemia (Coyne et al 2006).

Negative_regulation (suppression) of PTH in capsules associated with hypercalcemia

14) Confidence 0.55 Published 2006 Journal Therapeutics and Clinical Risk Management Section Body Doc Link PMC1936265 Disease Relevance 0.53 Pain Relevance 0

Although the oral administration of alfacalcidol showed no effects, 3 weeks of intermittent intravenous injection of maxacalcitol therapy decreased the serum intact PTH concentration from 597 pg/ml to 40 pg/ml, and the bone pain was greatly relieved.

Negative_regulation (decreased) of PTH associated with pain

15) Confidence 0.52 Published 2003 Journal Clin. Nephrol. Section Abstract Doc Link 14640244 Disease Relevance 1.24 Pain Relevance 0.17

The median decrease in PTH values from baseline was 88% (range, 33-99%).

Negative_regulation (decrease) of PTH

16) Confidence 0.50 Published 2001 Journal Clin. Chem. Section Body Doc Link 11325897 Disease Relevance 0 Pain Relevance 0

In conclusion, the subtotal parathyroidectomy or total parathyroidectomy with autotransplantation cause a rapid decrease of PTH level and the improvement of the clinical symptoms in patients with medical treatment resistant secondary hyperparathyroidism.

Negative_regulation (decrease) of PTH associated with hypercalcemia

17) Confidence 0.48 Published 2001 Journal Magy Seb Section Abstract Doc Link 11816132 Disease Relevance 0.94 Pain Relevance 0.13

We have noted a relationship between major involutive phenomena and a major reduction in iPTH and Ca serum levels, suggesting that a lower dose of cinacalcet may have been used.

Negative_regulation (reduction) of iPTH

18) Confidence 0.48 Published 2009 Journal Nephrology Dialysis Transplantation Section Body Doc Link PMC2644631 Disease Relevance 0.29 Pain Relevance 0

Our treatment reducing PTH levels resulted in a marked relief from pruritus and other symptoms, suggesting that patients in this condition, before undergoing surgical parathyroidectomy, may be usefully treated with this therapeutic modality.

Negative_regulation (reducing) of PTH associated with pruritus

19) Confidence 0.48 Published 1991 Journal Blood Purif. Section Abstract Doc Link 1801857 Disease Relevance 0.63 Pain Relevance 0.24

CONCLUSION: A rapid decrease in serum parathyroid hormone level after parathyroidectomy appears to suppress bone resorption, as well as cause a transient marked increase in bone formation and an increase in normal lamellar osteoid seams.

Negative_regulation (decrease) of serum parathyroid hormone in seams

20) Confidence 0.47 Published 2003 Journal Am. J. Kidney Dis. Section Body Doc Link 14520623 Disease Relevance 0 Pain Relevance 0

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