Endometrial bleeding in hormone replacement therapy users: preliminary findings regarding the role of matrix metalloproteinase 9 (MMP-9) and tissue inhibitors of MMPs

2001 ◽  
Vol 75 (2) ◽  
pp. 288-296 ◽  
Author(s):  
Martha Hickey ◽  
Jenny Higham ◽  
Mark Sullivan ◽  
Lyn Miles ◽  
Ian S Fraser
Author(s):  
Е.В. Маркелова ◽  
О.В. Овчинникова ◽  
А.С. Хохлова ◽  
Л.П. Догадова ◽  
А.В. Костюшко ◽  
...  

Оперативное вмешательство - один из основных методов лечения глаукомы. Однако развитие избыточного рубцевания созданных путей оттока определяет результат хирургического лечения в отдаленные сроки. Процессы рубцевания на данный момент недостаточно изучены. Цель исследования - оценка роли матриксной металлопротеиназы-9, ее ингибиторов в процессах рубцевания у больных с первичной открытоугольной глаукомой после оперативного лечения. Методика. Для выявления возможных маркеров избыточного рубцевания методом твердофазного иммуноферментного анализа определяли содержание матриксных металлопротеиназ-9, тканевых ингибиторов металлопротеиназ 2 и -3 в слезной жидкости у 37 пациентов с активной стадией первичной остроугольной глаукомы в динамике послеоперационного периода. Средний возраст пациентов составил 52,8 лет. В зависимости от исхода оперативного вмешательства все пациенты были разделены на 2 группы - с благоприятным исходом (без избыточного рубцевания) и с неблагоприятным исходом (с избыточным рубцеванием) на месте сформированных дополнительных путей оттока внутриглазной жидкости в послеоперационном периоде. Группа контроля включала 20 человек в возрасте от 50 до 66 лет без сопутствующей офтальмологической и соматической патологии в стадии обострения. Результаты. В динамике показано изменение концентрации матриксной металлопротеиназы-9 и ее ингибиторов в послеоперационном периоде. Анализ данных свидетельствует об обратной зависимости уровня матриксной металлопротеиназы-9 и тканевых ингибиторов металлопротеиназы 2 и 3 типов с исходом операции - чем выше концентрация металлопротеиназы-9 и ниже концентрация тканевых ингибиторов металлопротеиназ 2, -3 в слезной жидкости, тем выше вероятность неблагоприятного исхода в виде рубцевания сформированных дополнительных путей оттока внутриглазной жидкости в послеоперационном периоде. Заключение. Мониторинг уровня металлопротеиназ и их тканевых ингибиторов после проведения хирургического лечения пациентов с первичной открытоугольной глаукомой позволяет прогнозировать раннее рубцевание, дает возможность разработки новых методов лечения как в раннем, так и в позднем послеоперационном периоде. Surgery is one of the major treatments for glaucoma; however excessive scarring of created outflow patways affects the long-term outcome. At the present time, scarring processes are not sufficiently studied. Aim. To evaluate the role of matrix metalloproteinase 9 and its inhibitors in scarring after surgical treatment of open-angle glaucoma. Methods. Concentrations of matrix metalloproteinase 9 and tissue inhibitors of metalloproteinases 2 and 3 were measured in tear fluid of 37 patients (mean age, 52.8) with active primary open-angle glaucoma in dynamics during the postoperative period to identify possible markers of excessive scarring. Based on the surgery outcome, all patients were divided into two groups, with a favorable outcome (without excessive scarring) and an unfavorable outcome (with excessive scarring) in the created additional outflow pathways for the intraocular fluid in the postoperative period. The control group included 20 subjects aged 50-66 without eye disease or somatic disease at exacerbation stage. Results. Analysis of changes in concentrations of matrix metalloproteinase 9 and its inhibitors in the postoperative period showed their inverse relationship with the surgery outcome. The higher was the metalloproteinase 9 level and the lower the level of tissue inhibitors of metalloproteinases 2 and 3 the higher was the probability of unfavorable outcome evident as excessive scarring of the formed additional pathways for tear fluid outflow in the postoperative period. Conclusion. Postoperative monitoring of metalloproteinases and their tissue inhibitors allows to predict early scarring and to develop new treatments both in early and late postoperative periods.


2008 ◽  
Vol 44 (4) ◽  
pp. 439-449 ◽  
Author(s):  
Sumit Paul ◽  
Anamika Vivek Sharma ◽  
Pramathes Das Mahapatra ◽  
Partha Bhattacharya ◽  
Russel J. Reiter ◽  
...  

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Haseeb A Rahman ◽  
Ahmed Malik ◽  
Aesha Rahman ◽  
Saqib Chaudhry ◽  
Malik M Adil ◽  
...  

Background: There has been debate in the role of exogenous testosterone as a risk factor for stroke. Hormone replacement therapy (HRT) is considered a risk factor for stroke. The risk of ischemic stroke may increase when using testosterone-containing HRT. Methods: Using data from the observational component of the Women’s Health Initiative (WHI) [WHI Observational Study (OS)], we analyzed the 93,676 women aged 50-79 years, who participated in the OS over a period of 12±1 years. We compared the outcome of stroke in participants with reported use of a combination of testosterone and estrogen, estrogen alone, progesterone alone, and a combination of estrogen and progesterone, as recorded at the baseline visit. A logistic regression analysis was run to determine the odds of developing stroke. Results: Of the 93, 676 participants, 1772 used a combination of testosterone and estrogen (Estratest) HRT, 11,282 used progesterone alone, 10,808 used a combination of estrogen and progesterone, and 31,673 used estrogen alone. A smaller proportion of participants who developed an outcome of stroke had used Estratest as compared to estrogen alone or a combination of estrogen and progesterone (1.9% vs. 96.3% p=0.62). In the logistic regression, participants who had used Estratest were 1.2 times as likely to develop stroke as users of other hormone replacement therapy (OR 1.2 95%CI (0.96-1.6)), while women who had used progesterone only were 0.87 times less likely to develop stroke than users of other hormone replacement therapy (OR 0.874 95%CI (0.77-0.99)). After adjusting for confounders, the risk of developing stroke increased in users of Estratest (OR 1.25 95%CI (0.96-1.6) p=0.04), and decreased in users of progesterone only (OR 0.873 95%CI (0.77-0.99) p=0.038). Conclusion: Use of testosterone-containing HRT slightly increased the risk of stroke in women when compared to progesterone alone HRT, although this was not found to be significant. Stroke risk with Estratest may be considered to be similar to estrogen only and combination of estrogen plus progesterone HRT. Future studies are required to investigate these correlations.


2002 ◽  
Vol 3 (4) ◽  
pp. 310-315 ◽  
Author(s):  
Mastroianni Claudio M. ◽  
Liuzzi Grazia M. ◽  
d’Ettorre, Gabriella ◽  
Lichtner Miriam ◽  
Forcina Gabriele ◽  
...  

Scientifica ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jelena Kocić ◽  
Victor Villar ◽  
Aleksandra Krstić ◽  
Juan F. Santibanez

Transforming growth factor-beta (TGF-β1) is a potent inductor of matrix metalloproteinase-9 (MMP-9) in transformed cells. Recently, Ski-interacting protein (SKIP) has been described as a regulator of TGF-β1 signal transduction, but its role in the induction of cell malignance by TGF-β1 has not been fully elucidated so far. In the present study, we analyzed the role of SKIP on TGF-β1-induced MMP-9 production. Mouse transformed keratinocytes (PDV) were stably transfected with SKIP antisense construct. We observed that SKIP depletion provoked an enhancement in the expression of MMP-9 in response to TGF-β1 treatment. The downregulation of SKIP produced an enhancement in TGF-β1-activated ERK1,2 MAP kinase as well as increased transactivation of downstream Elk1 transcription factor. The increased MMP-9 production in response to TGF-β1 was dependent of MAPK activation as PD98059, an MEK inhibitor, reduced MMP-9 expression in SKIP antisense transfected cells. Thus, we propose SKIP as a regulatory protein in TGF-β1-induced MMP-9 expression acting by controlling ERK1,2 signaling in transformed cells.


2021 ◽  
Vol 11 (2) ◽  
pp. 277-289
Author(s):  
I. Lutsiv ◽  
A. Hudyma ◽  
S. Halnykina ◽  
O. Denefil

Introduction. Traumatic events are currently considered to be one of the topical issues. The progression of renal failure plays an important role in the pathogenesis of traumatic disease. It is essential to evaluate the ability of renal tubular epithelium to the urine osmotic concentration in order to indicate the direct renal tubular damage. A sodium-free water clearance (S-CH2O) is a sensitive indicator reflecting the kidneys ability to concentrate the urine. It is established that the renal functional state, the resistance of the kidneys to the development of various disorders depends on the estrogen concentration. The key mechanism of the indirect effect of estrogens on the kidneys is via their direct antioxidant action. However, the role of estrogens in the pathogenesis of oxidative and functional impairments of the kidneys in the presence of cranioskeletal trauma is insufficiently studied. There is no data available on the efficacy of hormone replacement therapy under those circumstances.The objective of research: to determine the pro-oxidant-antioxidant balance and renal concentrating capacity following the cranioskeletal trauma model in rats with bilateral ovariectomy in the period of late manifestations of the traumatic disease and evaluate the efficacy of hormone replacement therapy.Material and methods: The experimental studies were conducted on 64 white non-linear female rats weighing 200-220g. The experimental model of hypoestrogenism was performed through the surgical removal of gonads. The rats were subjected to the cranioskeletal model one month after removal of the gonads. Hormone replacement therapy (HRT) was used as a corrective treatment in the separate subgroup of gonadectomized rats subjected to the cranioskeletal trauma. The control groups consisted of intact animals and rats 1 month after removal of the gonads that were not injured. The renal functional state was determined via a water loading test in the control groups of animals and after 1 and 2 months of postrraumatic period. The sodium concentration, as well as the S-CH2O value was measured in serum and urine. The content of thiobarbituric acid reactive substances (TBARs) and catalase activity were determined in renal cortex and medulla. The prooxidant/antioxidant ratio (ProAntidex) was calculated based on the above data.The results and discussion. The conducted studies indicated the considerable decrease in ProAntidex value in renal cortex and medulla in the group of gonadectomized rats compared to the animals without gonadectomy after 1 month of the posttraumatic period, confirming the protective antioxidant role of estrogens in adequate renal function. The cranioskeletal trauma model led to the declined parameter value in renal cortex and medulla in both experimental groups after 1 month of the posttraumatic period. The prooxidant/antioxidant ratio was significantly decreased in the first month following the trauma in the gonadectomized rats as compared to the rats without the gonadectomy, and remained at the same level up to the 2nd month of the posttraumatic period. The identified abnormal value of ProAntidex in the posttraumatic period clearly affected the dynamics of S-CH2O. This parameter was reported as decreased in both experimental groups compared to the control. However, the parameter was substantially decreased 1 and 2 months after trauma under conditions of the gonadectomy.                   The administration of hexestrol and progesterone to the gonadectomized rats with trauma model resulted in the considerable increase in value of ProAntidex in renal cortex and medulla starting from the 1st day of the posttraumatic period compared to the animals without corrective medication. Moreover, it was accompanied by a statistically significant increase in S-CH2O rate, indicating the enhancement in the functional capacity of the renal tubules.Conclusions. The value of ProAntidex decreases in renal cortex and medulla in the group of gonadectomized female rats after 1 month of the posttraumatic period, and is significantly lower compared to the animals without removal of the gonads. The cranioskeletal trauma model leads to the substantially declined prooxidant/antioxidant ratio value in renal cortex and medulla, which is reported as considerably greater in the group of gonadectomized animals after 1 month of the posttraumatic period, showing no tendency to enhance after 2 months of the experiment. The administration of hormone replacement therapy to the gonadectomized rats is accompanied by the increase in ProAntidex value and S-CH2O rate compared to the animals without corrective medication.


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