Long-term treatment with finasteride induces apoptosis and pathological changes in female mice

2019 ◽  
Vol 38 (7) ◽  
pp. 762-774 ◽  
Author(s):  
AA Alkahtane ◽  
G Albasher ◽  
NK Al-Sultan ◽  
WS Alqahtani ◽  
S Alarifi ◽  
...  
Keyword(s):  
Serum Levels ◽  
Term Treatment ◽  
Androgenetic Alopecia ◽  
High Dose ◽  
Histopathological Analysis ◽  
Once Daily ◽  
Female Mice ◽  
Long Term Treatment ◽  
High Doses

Androgenetic alopecia is the most common type of alopecia, and it affects humans of both genders. Finasteride is a type II selective 5α-reductase inhibitor that is administered orally to treat androgenetic alopecia and benign prostatic hyperplasia in human males. However, its effect on the vital organs of females is unknown. This study was designed to investigate the effects of finasteride on the vital organs such as liver, kidney, and heart of female mice. To study the prospective effects of finasteride, female mice were orally administered two doses of finasteride (0.5 and 1.5 mg/kg) once daily for 35 days, and serum levels of various biochemical parameters and histopathology of various organs were examined. The results showed that serum levels of alkaline phosphatase were significantly increased by both high- and low-dose finasteride, whereas cholesterol was significantly increased by the high dose only. Creatine kinase was significantly increased by the high and low doses, whereas glucose was significantly decreased by both doses. Histopathological analysis and DNA damage assays showed that finasteride has adverse effects within both the short and the long periods in female mice. In addition, the proapoptotic genes Bax and caspase-3 were significantly increased by high dose finasteride, whereas the antiapoptotic gene Bcl-2 was significantly decreased by the low and high doses. In conclusion, finasteride is not currently approved for therapeutic use in females, and the findings in this study suggest caution in any future consideration of such use.

1608: Long-Term Treatment with High Doses of Sildenafil Does Not Up-Regulate the Levels of Phosphodiesterase 5 (Pde5) in the Rat Penis

2004 ◽  
Vol 171 (4S) ◽  
pp. 424-424 ◽  
Author(s):  
Monica G. Ferrini ◽  
Eliane G. Valente ◽  
Jacob Rajfer ◽  
Nestor F. Gonzalez-Cadavid
Keyword(s):  
Term Treatment ◽  
Long Term Treatment ◽  
High Doses ◽  
Phosphodiesterase 5

Long-term treatment of acromegaly with the slow-release somatostatin analogue lanreotide

1994 ◽  
Vol 131 (1) ◽  
pp. 20-26 ◽  
Author(s):  
Josef Marek ◽  
Václav Hána ◽  
Michal Kršek ◽  
Vlasta Justová ◽  
France Catus ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Slow Release ◽  
Serum Levels ◽  
Term Treatment ◽  
Somatostatin Analogue ◽  
Tumour Mass ◽  
Long Term Treatment ◽  
Active Acromegaly ◽  
One Year

Marek J, Hána V. Kršek M. Justová V, Catus F, Thomas F. Long-term treatment of acromegaly with the slow-release somatostatin analogue lanreotide. Eur J Endocrinol 1994;131:20–6. ISSN 0804–4643 Thirteen patients with active acromegaly despite previous surgery were treated with 30 mg lanreotide im twice a month for 9 months. In 10 subjects the treatment continued to 19 months. GH serum levels of all patients decreased significantly from an initial value of 32.0 (29.4) μg/l [median (standard error of median)] to 10.0 (3.6) and 19.1 (5.7) after 3 and 9 months of treatment, respectively. In the 10 patients with the treatment longer than one year the decrease in GH was from 46.8 (29.4) μg/l to 12.5 (5.0) and 16.1 (5.3) after 13 and 19 months, respectively. IGF-I serum levels decreased significantly from 1193 (73)μg/l to 782 (99) and 621 (103) after 3 and 9 months, respectively, and were normalized in 3 patients. In the 10 patients treated for longer than one year, levels decreased significantly from 1318 (74)μg/l to 653 (170) and 742 (180) after 13 and 19 months, respectively. IGF BP-3 levels were reduced to the normal range in 6 patients and decreased from 8.7 (1.5)mg/l to 6.4 (0.8) and to 5.4 (1.0) after 3 and 9 months, respectively. In the patients with the 19 months treatment the decrease was from 9.3 (1.6) mg/l to 3.9 (0.9) and 4.8 (0.9) after 13 and 19 months, respectively. The IGF BP-3 to IFG I ratio increased in 7 patients. This elevation significantly correlated with the decrease in bioassayable somatomedin. Prolactin serum levels fell in all patients with increased prolactin secretion. Testosterone plasma levels increased in 4 out of 5 men without replacement therapy. Clinical improvement was observed in all patients. A reduction of tumour mass was observed in five patients and complete disappearance of the tumour in one subject. All patients complained of mild abdominal pain and softened stools for several days following the injections. However, these side effects never required interruption of treatment. Asymptomatic microlithiasis was seen in only one patient after 13 months, which led to treatment being suspended for a period of 3 months after which it was resumed. Fasting serum insulin and insulin area under the curve (AUC) after oral glucose tolerance test (OGTT) fell in all patients. Fasting blood glucose, fructosamine and glucose AUC after OGTT slightly increased during the treatment, but all blood glucose levels (fasting and during OGTT) remained within normal ranges. Lanreotide appears to be a safe and effective treatment in patients with active acromegaly unresolved by surgery. The long-acting formulation avoids the drawbacks associated with either repeated daily injections or continuous infusions of somatostatin analogues. Josef Marek, Third Department of Medicine, Charles University, U nemocnice 1, 128 21 Praha 2, The Czech Republic

scholarly journals Successful and safe long‐term treatment of cerebral aspergillosis with high‐dose voriconazole guided by therapeutic drug monitoring

2018 ◽  
Vol 85 (1) ◽  
pp. 266-269 ◽  
Author(s):  
Pier Giorgio Cojutti ◽  
Maria Merelli ◽  
Lorenzo Allegri ◽  
Giuseppe Damante ◽  
Matteo Bassetti ◽  
...  
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Term Treatment ◽  
Therapeutic Drug ◽  
High Dose ◽  
Long Term Treatment

scholarly journals Successful Long-term Treatment with Once-daily Injection of Low-dose Octreotide in an Aged Patient with Insulinoma

2005 ◽  
Vol 52 (5) ◽  
pp. 629-634 ◽  
Author(s):  
Takuyuki KATABAMI ◽  
Hiroyuki KATO ◽  
Naoko SHIRAI ◽  
Satoru NAITO ◽  
Nobuhiko SAITO
Keyword(s):  
Low Dose ◽  
Term Treatment ◽  
Daily Injection ◽  
Aged Patient ◽  
Once Daily ◽  
Long Term Treatment

Effect of short- and long-term treatment with omeprazole on the absorption and serum levels of cobalamin

1996 ◽  
Vol 10 (4) ◽  
pp. 541-545 ◽  
Author(s):  
B. E. SCHENK ◽  
H. P. M. FESTEN ◽  
E. J. KUIPERS ◽  
E. C. KLINKENBERG-KNOL ◽  
S. G. M. MEUWISSEN
Keyword(s):  
Serum Levels ◽  
Term Treatment ◽  
Long Term Treatment ◽  
Short And Long Term

scholarly journals Intermittent micafungin for prophylaxis in a rat model of chronic Candida albicans gut colonization

2020 ◽  
Vol 75 (10) ◽  
pp. 2919-2924
Author(s):  
Peter Warn ◽  
Pia Thommes ◽  
Andrew Sharp ◽  
Abdul Sattar ◽  
Nasrullah Undre ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Rat Model ◽  
Vehicle Control ◽  
Antifungal Prophylaxis ◽  
High Dose ◽  
Once Daily ◽  
Systemic Dissemination ◽  
Long Term Treatment ◽  
Gastrointestinal Colonization

Abstract Background During antifungal prophylaxis, micafungin is generally infused IV once daily over 1 h. In practice, less-frequent dosing could improve the quality of life in patients requiring long-term treatment or prophylaxis. The feasibility of this approach was assessed using humanized doses of daily or infrequent micafungin regimens. Objectives To evaluate the effectiveness of intermittent high-dose micafungin, simulating human exposure, for prophylaxis of invasive candidiasis in a rat model of chronic Candida albicans gastrointestinal colonization and systemic dissemination. Methods Two weeks post-infection with an oral challenge of C. albicans, Sprague–Dawley rats were immunocompromised with a cytotoxic drug and a steroid. Rats received IV infusions of: daily vehicle control; daily subcutaneous micafungin (20 mg/kg SC); high-dose micafungin (20 mg/kg bolus SC + 80 mg/kg infusion/72 h, to simulate intermittent human dosing of 300 mg/72 h); or daily fluconazole by mouth (10 mg/kg PO). The effects of antifungal prophylaxis on faecal fungal burden and systemic C. albicans dissemination were evaluated. Results A rat model of chronic C. albicans gastrointestinal colonization and systemic dissemination was established, characterized by a sustained microbiological burden over 29 days and fungal recovery from normally sterile tissues. Using this model, intermittent high-dose micafungin (delivered via iPrecio pumps) to simulate humanized doses of 300 mg/72 h was significantly more effective than vehicle control, as effective as once-daily micafungin and similar to daily fluconazole at reducing faecal burden and preventing systemic dissemination. Conclusions These data indicate that intermittent high-dose micafungin can be as effective as daily therapy, supporting clinical assessment in high-risk patients requiring long-term antifungal prophylaxis.

Will a once-weekly anticoagulant for the treatment and secondary prevention of thromboembolism improve adherence?

2009 ◽  
Vol 101 (03) ◽  
pp. 422-427 ◽  
Author(s):  
Louise Maillardet ◽  
Yshai Yavin ◽  
Alexander T. Cohen
Keyword(s):  
Secondary Prevention ◽  
Depressive Disorders ◽  
Term Treatment ◽  
Bisphosphonate Treatment ◽  
Weekly Administration ◽  
Once Daily ◽  
New Anticoagulants ◽  
Improved Outcomes ◽  
Long Term Treatment

SummaryOral anticoagulation, most commonly with warfarin once daily, has long been the main form of long-term treatment and secondary prevention of thromboembolism. The efficacy of warfarin has been established in clinical trials, but problems with unstable anticoagulation with international normalized ratios (INRs) outside the recommended range due to incorrect dosing, drug and food interactions, and with adherence and persistence have been reported in practice. Poor adherence and persistence are serious problems because they result in out-of-range INRs. Many new thromboembolic events, such as strokes, occur when INRs are out-of-range or after warfarin discontinuation. Among the new anticoagulants currently being investigated, some offer the possibility of more stable anticoagulation and weekly administration. Less frequent dosing schedules generally improve adherence. In many cases, such as bisphosphonate treatment for osteoporosis, and the long-term treatment of depressive disorders or multiple sclerosis, adherence to, and persistence with, weekly dosing is improved compared with daily dosing, and most patients prefer weekly dosing. The advent of novel anticoagulants such as idraparinux with its long half-life offers hope for improved adherence with anticoagulation, and ultimately improved outcomes.

scholarly journals Effects of long-term treatment with resveratrol and subcutaneous and oral estradiol administration on pituitary function in rats

2006 ◽  
Vol 189 (1) ◽  
pp. 77-88 ◽  
Author(s):  
Martina Böttner ◽  
Julie Christoffel ◽  
Hubertus Jarry ◽  
Wolfgang Wuttke
Keyword(s):  
Serum Levels ◽  
Term Treatment ◽  
Prolactin Secretion ◽  
Gnrh Receptor ◽  
Female Rats ◽  
Pituitary Function ◽  
Ovx Rats ◽  
Long Term Treatment

Hormone replacement therapy (HRT) has been used for several decades to treat menopausal discomforts. However, in the light of recent studies that draw attention to the potential hazards of conventional HRT, various attempts have been undertaken to search for alternatives to classical HRT. Phytoestrogens are claimed to be capable of positively influencing menopausal symptoms, including hot flushes. We designed a long-term study of 3 months to assess the effects of subcutaneous and orally fed 17β-estradiol (E2), as well as the actions of resveratrol (RES) on pituitary function in female rats. Our results have demonstrated that RES binds with a 10-fold lower affinity to estrogen receptor (ER)-α than to ERβ. The data from the in vivo study revealed that a dosage of 5 μg and 50 μg RES/kg bodyweight per day given to ovariectomized (OVX) rats achieved serum levels of 1.0 and 8.1 μM respectively. Long-term treatment of OVX rats with RES revealed no estrogenic potential on pituitary function in vivo as assessed by LH and prolactin secretion and by regulation of mRNAs for LHα, LHβ, and GnRH receptor. Subcutaneous treatment with E2 in silastic capsules exerted stronger effects on LH and prolactin secretion, as well as on LHβ, LHα, GnRH receptor, and ERβ mRNA regulation compared with orally applied estradiol benzoate despite comparable serum levels. Levels of aryl hydrocarbon receptor (AhR) mRNA in the pituitary were increased following OVX and attenuated by long-term E2 treatment, whereas RES did not modulate AhR mRNA expression.

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