Objetive:The aim was to assess the evolution of tumor size and prolactin (PRL) levels in patients with micro and macroprolactinomas diagnosed and treated with dopamine agonists during fertile age, and the effects of suspension of drugs after menopause. Subjects and methods: Retrospective study, 29 patients with prolactinomas, 22 microadenomas and 7 macroadenomas, diagnosed during their fertile age were studied in their menopause; treatment was stopped in this period. Age at menopause was 49 ± 3.6 years. The average time of treatment was 135 ± 79 months. The time of follow-up after treatment suspension was 4 to 192 months. Results: Pre-treatment PRL levels in micro and macroadenomas were 119 ± 57 ng/mL and 258 ± 225 ng/mL, respectively. During menopause after treatment suspension, and at the latest follow-up: in microadenomas PRL levels were 23 ± 13 ng/mL and 16 ± 5.7 ng/mL, respectively; in macroadenomas, PRL levels were 20 ± 6.6 ng/mL and 25 ± 18 ng/mL, respectively. In menopause after treatment suspension, the microadenomas had disappeared in 9/22 and had decreased in 13/22. In the group of patients whose tumor had decreased, in the latest follow-up, tumors disappeared in 7/13 and remained unchanged in 6/13. In macroadenomas, after treatment suspension 3/7 had disappeared, 3/7 decreased and 1/7 remained unchanged. In the latest control in the 3 patients whose tumor decreased, disappeared in 1/3, decreased in 1/3 and there was no change in the remaining. Conclusions: Normal PRL levels and sustained reduction or disappearance of adenomas were achieved in most of patients, probably due to the decrease of estrogen levels. Dopamine agonists might be stopped after menopause in patients with prolactinomas.Arch Endocrinol Metab. 2016;60(1):42-6
The biosynthesis of met-enkephalin in human pituitary and human pituitary adenomas is still not well known. In this work, we studied the processing of proenkephalin-derived peptides in postmortem human pituitary (PMHP), ACTH-producing adenomas (ACTH-PA), nonfunctioning adenomas (NFA), and GH-producing adenomas (GH-PA). ACTH-PA contained at least 10 times more proenkephalin-derived peptides than PMHP, NFA,and GH-PA. Proenkephalin processing was different in the four tested tissues. In ACTH-PA, proenkephalin was processed to high-, intermediate-, and low-mol-wt products. The highest met-enkephalin-containing peptides levels corresponded to intermediate and low-mol-wt materials, although met-enkephalinArg-Phe and synenkephalin immunoreactivity appeared only in high-mol-wt peptides. In PMHP and NFA, met-enkephalin-Arg-Phe immunoreactivity was detected in intermediate- and low-mol-wt materials, and it was absent in GH-PA. Immunoblotting of ACTH-PA showed that met-enkephalin-Arg-Phe immunoreactivity corresponded to peptides of 44, 32-30, 27, and 17 kDa. The 32-30 and 17-kDa molecules were localized in the nuclear fraction where they were extracted after enzymatic digestion with DNase I. Plasmatic met-enkephalin levels did not increase in patients with Cushing's disease, suggesting that the pentapeptide stored in ACTH-PA was not released to the general circulation. In conclusion, we demonstrated that only ACTH-PA contained high levels of proenkephalin peptides, which were stored in cytoplasm organelles and in the nucleus, probably bound to chromatin. These results suggest an adenoma-specific physiological role of proenkephalin products.
This study evaluated the effect of resveratrol (RES) on the prevention of medication‐related osteonecrosis of the jaws (MRONJ) in ovariectomized (OVX) rats treated with zoledronate (ZOL). Fifty rats were distributed in five groups: SHAM (n = 10): non‐ovariectomy + placebo; OVX (n = 10):ovariectomy + placebo; OVX + RES (n = 10):ovariectomy + resveratrol; OVX + ZOL (n = 10):ovariectomy + placebo + zoledronate; and OVX + RES + ZOL (n = 10):ovariectomy + resveratrol + zoledronate. The mandibles left sides were analyzed with micro‐CT, histomorphometry, and immunohistochemistry. On the right side, bone markers gene expression was analyzed by qPCR. ZOL increased the percentage of necrotic bone and reduced the neo‐formed bone compared to groups not receiving ZOL (p < 0.05). RES impacted the tissue healing pattern in OVX + ZOL + RES, reduced inflammatory cell infiltrate, and improved bone formation in the extraction site. Osteoblasts, alkaline phosphatase (ALP)‐, and osteocalcin (OCN)‐immunoreactive cells were lower in OVX‐ZOL than in SHAM, OVX, and OVX‐RES. The OXV‐ZOL‐RES had fewer osteoblasts and ALP‐ and OCN‐cells than the SHAM and OVX‐RES. The tartrate‐resistant acid phosphatase (TRAP)‐positive cells were reduced in the presence of ZOL (p < 0.05), while the TRAP mRNA levels increased with ZOL treatment, with or without resveratrol, compared with the other groups (p < 0.05). RES alone increased superoxide dismutase levels compared to OVX + ZOL and OVX + ZOL + RES (p < 0.05). In conclusion, resveratrol reduced the tissue impairment severity induced by ZOL; however, it could not prevent the occurrence of MRONJ.
Photoaging is the result of the combination of chronologic aging and the exposition to several extrinsic agents that trigger oxidative stress. It is characterized by dermal and epidermal alterations, such as wrinkles, dryness, sagging, roughness and pigmentary changes. Some of these signs are the result of an impairment of the Extracellular Matrix (ECM) components, which represent the structural and functional dermal support in healthy skin, but are diminished or dysfunctional in aged skin.
Background : The use of drugs such as bisphosphonates has been linked to adverse effects, such as osteonecrosis of the jaws associated with medication. Resveratrol has characteristics anti-oxidant, anti-inflammatory, antiresorptive and effects on apoptosis control and this substance could be important in preventing the occurrence of MRONJ associated with bisphosphonates.Aim/Hypothesis : This study aimed at verifying the effect of resveratrol (RESV) on the prevention of medication-related osteonecrosis of the jaws (MRONJ) in estrogen-deficient rats treated with zoledronate (ZLD). Material and Methods: Fifth adult Wistar rats distributed in the following groups-(1) OVT; RESV ( n -10)-ovariectomy; resveratrol; (2) OVT; PLA ( n -10)-ovariectomy; placebo; (3) OVT; ZLD ( n -10)-ovariectomy; zoledronate, (4) OVT; RESV; ZLD ( n -10)-ovariectomy; resveratrol; zoledronate, (5) SHAM;PLAC ( n -10)-no ovariectomy; placebo. The ONM was induced by means of the exodontia of the lower molars bilater-ally. After euthanasia, the left hemi-jaws were submitted to computerized microtomography (Micro-CT) and after that to immunohistochemistry. The right hemi-jaws were collected for analysis of gene expression. The animals' blood was also collected for the serum analysis of the Carboxyterminal Telopeptide of Type I Collagen (CTX), through Elisa. Data were submitted to statistical analysis using the ANOVA Tukey or Kruskal Wallis Dunn tests, with a significance level of 5%.Results : Histomorphometric analysis showed that zoledronate increased the percentage of non-vital bone tissue (TONV) and reduced the percentage of (neo-formed bone tissue) TONF compared to the groups that did not receive zoledronate ( P < 0.05). In addition, when resveratrol was administrated isolated, higher TONF values were observed comparing to OVT;ZOL; PLAC group ( P < 0.05). The number of TRAP-positive cells reduced in the presence of zoledronate ( P < 0.05), while the mRNA levels of TRAP increased with ZLD treatment, with or without resveratrol in relation to the other groups ( P < 0.05). Treatment with resveratrol increased SOD levels when compared to OVT; ZLD; PLAC and OVT; ZLD; RESV ( P < 0.05). Conclusion and ClinicalImplications : It can be concluded that resveratrol reduced MRONJ induced by zoledronic acid in estrogen-deficient rats. And as a clinical implications the chronic and systemic use of resveratrol may prevent the appearance of osteonecrosis of the jaws associated with medications.
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