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1.
BMC Complement Med Ther ; 23(1): 187, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37286957

RESUMO

INTRODUCTION: This study was motivated by the increasing global incidence of benign prostatic hyperplasia (BPH) and the promising potential of nutraceuticals as complementary therapies in ameliorating its burden. We report the safety profile of C. esculenta tuber extracts, a novel nutraceutical in benign prostate hyperplasia in a rat model. METHODS: In this study, forty-five male albino rats were randomly assigned to 9 groups of 5 rats each. Group 1 (normal control) received olive oil and normal saline. Group 2 (BPH untreated group) received 3 mg/kg of testosterone propionate (TP) and normal saline, and group 3 (positive control) received 3 mg/kg of TP and 5 mg/kg of finasteride. Treatment groups 4, 5, 6, 7, 8, and 9 received 3 mg/kg of TP and a middle dose (200 mg/kg) of LD50 of ethanol crude tuber extract of C. esculenta (ECTECE) or hexane, dichloromethane, butanone, ethyl acetate and aqueous fractions of ECTECE respectively for a period of 28 days. RESULTS: The negative controls showed a significant (p < 0.05) increase in mean relative prostate weight (approximately 5 times) as well as a reduction in relative testes weight (approximately 1.4 times less). There was no significant (p > 0.05) difference in the mean relative weights of most vital organs: liver, kidneys, and heart. This was also observed in hematological parameters: RBC, hemoglobin, HCT, MCV, MCH, MCHC, and platelets counts. In general, we note that the effects of the well-established drug finasteride on the biochemical parameters and histology of selected organs are comparable to those of C. esculenta fractions. CONCLUSION: This study demonstrates that C. esculenta tuber extracts provide potentially safe nutraceutical if applied in the management of benign prostate hyperplasia based on a rat model.


Assuntos
Colocasia , Hiperplasia Prostática , Propionato de Testosterona , Animais , Masculino , Ratos , Finasterida/uso terapêutico , Hiperplasia/tratamento farmacológico , Hiperplasia/patologia , Extratos Vegetais/efeitos adversos , Extratos Vegetais/uso terapêutico , Próstata , Hiperplasia Prostática/tratamento farmacológico , Solução Salina/uso terapêutico , Propionato de Testosterona/uso terapêutico
2.
Bull Exp Biol Med ; 173(5): 680-686, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36210419

RESUMO

In order to optimize the testosterone model of benign prostatic hyperplasia, we studied the effect of castration and different doses of testosterone on the induction of the proliferative process in the prostate of Wistar rats. It was shown that 4-week subcutaneous administration of testosterone propionate in a dose of 20 mg/kg causes pronounced proliferative and hemodynamic disorders in the dorsolateral gland morphologically similar in castrated and non-castrated males. Administration of testosterone in a dose of 3 mg/kg had no significant effect on the dynamics of the pathological process in non-operated rats and normalized the structure of the gland in castrated animals. Morphological study showed that castration of males provides no visible advantages in reproducing the testosterone model of benign prostatic hyperplasia. The proposed non-traumatic modification of the model with a high dose of testosterone has good reproducibility and sensitivity to therapeutic agents, as shown by the example of finasteride.


Assuntos
Hiperplasia Prostática , Propionato de Testosterona , Animais , Finasterida/farmacologia , Humanos , Masculino , Orquiectomia , Hiperplasia Prostática/induzido quimicamente , Hiperplasia Prostática/tratamento farmacológico , Hiperplasia Prostática/patologia , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Testosterona , Propionato de Testosterona/farmacologia , Propionato de Testosterona/uso terapêutico
3.
Life Sci ; 291: 120240, 2022 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-34942164

RESUMO

AIMS: In this study, we used a near-infrared laser (NIR) to increase the potency of silver nanoparticles (AgNPs) to develop a novel, less invasive, and simple photothermal therapy technique for benign prostate hyperplasia (BPH). MATERIALS AND METHODS: The shape, particle size, and zeta-potential of polyvinylpyrrolidone coated-AgNPs (PVP-AgNPs) were determined using transmission electron microscopy (TEM), Zeta-potential, and Particle size analyzer (ELSZ). To induce BPH, thirty-six male Sprague-Dawley (SD) rats were given intramuscular (i.m) injections of testosterone propionate (TP) at 5 mg/kg body weight (b.w)/day suspended in 0.1 ml of olive oil for 14 days. Photothermal therapy with AgNPs-NIR for 14 days was carried out. Prostate size, prostate index (PI), dihydrotestosterone (DHT), prostate-specific antigen (PSA), gross, hepatic, and renal toxicity, as well as antioxidant activity, apoptosis, and angiogenesis markers in prostatic tissues were measured. Histological examinations of prostates and biocompatibility of NIR-AgNPs on vital organs were also performed. KEY FINDINGS: The aggregated spherical AgNPs with a mean size of 50-90 nm and a Zeta potential of -53.22 mV displayed high effectiveness in the NIR (532 nm-1 W) region by decreasing prostate size, PI, DHT, and PSA in BPH rats with no signs of gross, hepatic, or renal damage. As compared to alternative therapies, hyperthermia therapy increased antioxidant activities, induced apoptosis, inhibited angiogenesis, reduced histological alterations in the prostates of BPH rats, and improved biocompatibility of the vital organs. SIGNIFICANCE: The current study demonstrated the effectiveness of plasmonic AgNPs photothermal therapy in the treatment of BPH.


Assuntos
Nanopartículas Metálicas/uso terapêutico , Fototerapia/métodos , Hiperplasia Prostática/tratamento farmacológico , Animais , Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Di-Hidrotestosterona/uso terapêutico , Sistemas de Liberação de Medicamentos/métodos , Finasterida/farmacologia , Hiperplasia/patologia , Masculino , Nanopartículas Metálicas/química , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/fisiopatologia , Extratos Vegetais/farmacologia , Próstata/patologia , Hiperplasia Prostática/fisiopatologia , Ratos , Ratos Sprague-Dawley , Prata/química , Ressonância de Plasmônio de Superfície/métodos , Testosterona/efeitos adversos , Propionato de Testosterona/uso terapêutico
4.
Exp Parasitol ; 202: 15-21, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31078550

RESUMO

Toxoplasma gondii is an opportunistic zoonotic protozoan that exceeds neurological and congenital impact sequence to reactivating latent toxoplasmosis especially under immunosuppression. Sex-associated hormones influence the severity of Toxoplasma infection. Thus, our study aimed to compare toxoplasmosis associated morbidity in both male and female mice and to monitor the response to anti-Toxoplasma therapeutics fortified with sex hormones in comparison to presently used drugs. Twenty male and 20 female mice were infected with ME49 Toxoplasma strain. The morbidity was assessed in the chronic stage in both sexes by estimating brain cyst burden, brain histopathological examination and monitoring serum anti-Toxoplasma IL-12 using ELISA method. Another 40 male and 40 female mice were infected with ME49 Toxoplasma strain then after 6 weeks received different treatment regimens including Atovaquone, Spiramycin, Metronidazole, Estradiol benzoate and Testoserone propionate either as a monotherapy or as a combination. Treatment response was monitored by scoring mice activity and brain cyst burden. This study showed that female mice demonstrated higher cyst burden and manifested more pathological reactions than male mice. While, the IL-12 serum level was significantly higher in male than female mice. Also, it is proved that the Toxoplasma cyst number was reduced significantly when used testosterone/atovaquone, or testosterone/spiramycin/metronidazole combined regimen in female mice groups. While for male mice, the combined therapy of spiramycin/metronidazole was the superior one. Accordingly, combined therapy with sex hormones is a promising strategy for discovering new therapeutic regimens for treating latent toxoplasmosis especially in female.


Assuntos
Coccidiostáticos/uso terapêutico , Toxoplasmose Animal/epidemiologia , Animais , Anticorpos Antiprotozoários/sangue , Atovaquona/uso terapêutico , Encéfalo/parasitologia , Encéfalo/patologia , Doença Crônica , Quimioterapia Combinada , Ensaio de Imunoadsorção Enzimática , Estradiol/análogos & derivados , Estradiol/uso terapêutico , Feminino , Imunoglobulina G/sangue , Interleucina-12/sangue , Masculino , Metronidazol/uso terapêutico , Camundongos , Morbidade , Fatores Sexuais , Espiramicina/uso terapêutico , Propionato de Testosterona/uso terapêutico , Toxoplasma/fisiologia , Toxoplasmose Animal/tratamento farmacológico
5.
Urology ; 116: 229.e1-229.e6, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29596864

RESUMO

OBJECTIVE: To determine whether low androgen status impacts erectile function by regulating the expression of the G protein-coupled P2Y receptors (P2Y1, P2Y2, P2Y4, and P2Y6) in the corpus cavernosum penis of rats. MATERIALS AND METHODS: A total of 36 healthy, 8-week-old, male Sprague-Dawley rats were randomly allocated into 6 groups: 4 weeks of androgen replacement therapy post castration (group A); 4 weeks post castration (group B); 4 weeks post sham operation (group C); 8 weeks of androgen replacement therapy post castration (group D); 8 weeks post castration (group E); and 8 weeks post sham operation (group F). The ratio of maximum intracavernous pressure/mean arterial pressure was measured for every group and detected the expression of P2Y1, P2Y2, P2Y4, and P2Y6 in the rat corpus cavernosum penis of every group. RESULTS: The ratio of maximum intracavernous pressure/mean arterial pressure significantly declined in the castration group compared with the control group (P <.01). The expression of P2Y1, P2Y2, P2Y4, and P2Y6 and the ratio of the phosphorylated endothelial nitric oxide synthase (eNOS)/eNOS proteins were significantly lower in the castration group vs treatment or control (P <.01) whereas they were significantly lower in the group of 8 weeks vs 4 weeks post castration (P <.05). The rat serum testosterone levels in every group were positively correlated with the protein levels of P2Y1, P2Y2, P2Y4, and P2Y6. CONCLUSION: Downregulation of the expression of the P2Y1, P2Y2, P2Y4, and P2Y6 receptors that reduces the ratio of phosphorylated eNOS/eNOS and eNOS activity may be one of the important mechanisms of erectile dysfunction caused by low androgen status.


Assuntos
Disfunção Erétil/sangue , Pênis/metabolismo , Receptores Purinérgicos P2Y/metabolismo , Testosterona/sangue , Animais , Modelos Animais de Doenças , Regulação para Baixo , Disfunção Erétil/etiologia , Disfunção Erétil/patologia , Disfunção Erétil/fisiopatologia , Terapia de Reposição Hormonal , Humanos , Injeções Subcutâneas , Masculino , Óxido Nítrico Sintase Tipo III/metabolismo , Orquiectomia , Ereção Peniana/fisiologia , Pênis/patologia , Pênis/fisiopatologia , Fosforilação/fisiologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Testosterona/fisiologia , Propionato de Testosterona/uso terapêutico
6.
Endocrinology ; 154(9): 3294-304, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23782943

RESUMO

Gonadal steroids are potent regulators of adult neurogenesis. We previously reported that androgens, such as testosterone (T) and dihydrotestosterone (DHT), but not estradiol, increased the survival of new neurons in the dentate gyrus of the male rat. These results suggest androgens regulate hippocampal neurogenesis via the androgen receptor (AR). To test this supposition, we examined the role of ARs in hippocampal neurogenesis using 2 different approaches. In experiment 1, we examined neurogenesis in male rats insensitive to androgens due to a naturally occurring mutation in the gene encoding the AR (termed testicular feminization mutation) compared with wild-type males. In experiment 2, we injected the AR antagonist, flutamide, into castrated male rats and compared neurogenesis levels in the dentate gyrus of DHT and oil-treated controls. In experiment 1, chronic T increased hippocampal neurogenesis in wild-type males but not in androgen-insensitive testicular feminization mutation males. In experiment 2, DHT increased hippocampal neurogenesis via cell survival, an effect that was blocked by concurrent treatment with flutamide. DHT, however, did not affect cell proliferation. Interestingly, cells expressing doublecortin, a marker of immature neurons, did not colabel with ARs in the dentate gyrus, but ARs were robustly expressed in other regions of the hippocampus. Together these studies provide complementary evidence that androgens regulate adult neurogenesis in the hippocampus via the AR but at a site other than the dentate gyrus. Understanding where in the brain androgens act to increase the survival of new neurons in the adult brain may have implications for neurodegenerative disorders.


Assuntos
Androgênios/metabolismo , Giro Denteado/metabolismo , Neurogênese , Neurônios/metabolismo , Fármacos Neuroprotetores/metabolismo , Receptores Androgênicos/metabolismo , Transdução de Sinais , Antagonistas de Androgênios/toxicidade , Síndrome de Resistência a Andrógenos/induzido quimicamente , Síndrome de Resistência a Andrógenos/tratamento farmacológico , Síndrome de Resistência a Andrógenos/metabolismo , Androgênios/química , Androgênios/farmacologia , Androgênios/uso terapêutico , Animais , Biomarcadores/metabolismo , Castração/efeitos adversos , Sobrevivência Celular/efeitos dos fármacos , Giro Denteado/citologia , Giro Denteado/efeitos dos fármacos , Giro Denteado/patologia , Proteínas do Domínio Duplacortina , Proteína Duplacortina , Resistência a Medicamentos , Terapia de Reposição Hormonal , Masculino , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Mutantes/agonistas , Proteínas Mutantes/antagonistas & inibidores , Proteínas Mutantes/metabolismo , Células-Tronco Neurais/citologia , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Células-Tronco Neurais/patologia , Neurogênese/efeitos dos fármacos , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/patologia , Neuropeptídeos/metabolismo , Fármacos Neuroprotetores/antagonistas & inibidores , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Ratos , Ratos Sprague-Dawley , Receptores Androgênicos/química , Receptores Androgênicos/genética , Transdução de Sinais/efeitos dos fármacos , Propionato de Testosterona/antagonistas & inibidores , Propionato de Testosterona/farmacologia , Propionato de Testosterona/uso terapêutico
7.
Clin Endocrinol (Oxf) ; 79(2): 243-51, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23278834

RESUMO

INTRODUCTION: The aim of this study was to demonstrate the influences of three different treatment strategies on biochemical parameters and testicular volume (TV) in patients with idiopathic hypogonadotropic hypogonadism (IHH). SUBJECTS DESIGN AND METHODS: Seventy-seven never-treated patients with IHH and age and body mass index (BMI)-matched 42 healthy controls were analysed in a retrospective design. Twenty-eight patients were treated with testosterone esters (TE), 25 patients were treated with human chorionic gonadotropin (hCG) and 24 patients were treated with testosterone gel (TG). Biochemical parameters, tanner stages (TS) and TV were evaluated before and after 6 months of treatment. RESULTS: Pretreatment TV, TS and biochemical test results were similar among the three treatment subgroup. In the TE-treated group, BMI, haemoglobin, haematocrit, creatinine, triglyceride, total testosterone (TT), TS and TV increased, but HDL-cholesterol (C) and urea level decreased significantly. In the hCG-treated group, triglyceride level decreased, and luteinizing hormone level, TS and TV increased significantly. BMI, TT, TS and TV increased, and leucocyte count, total-C, HDL-C levels decreased significantly in the TG-treated patients. No treatment type resulted in any changes in insulin resistance markers. CONCLUSION: hCG treatment resulted in favourable effects particularly on TV and lipid parameters. When TV improvement is considered less important, TG treatment may be a better option for older patients with IHH because of its easy use, neutral effects on triglyceride, haemoglobin and haematocrit, and its beneficial effects on total cholesterol level.


Assuntos
Hipogonadismo/tratamento farmacológico , Testosterona/uso terapêutico , Gonadotropina Coriônica/uso terapêutico , Géis/uso terapêutico , Humanos , Masculino , Tamanho do Órgão , Estudos Retrospectivos , Testículo/anatomia & histologia , Testículo/efeitos dos fármacos , Testosterona/administração & dosagem , Testosterona/análogos & derivados , Propionato de Testosterona/análogos & derivados , Propionato de Testosterona/uso terapêutico , Adulto Jovem
8.
Restor Neurol Neurosci ; 31(2): 169-76, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23247060

RESUMO

PURPOSE: To investigate the effects of the androgen testosterone propionate (TP), on regeneration of the recurrent laryngeal nerve (RLN) after unilateral crush injury using assessment of vocal fold mobility (VFM) as a measure of behavioral recovery. METHODS: 48 adult male rats underwent standardized crush injury of left RLN and received treatment in the form of 2 silastic capsules containing TP or controls receiving a blank capsule (untreated). Direct laryngoscopic assessment of vocal cord mobility was performed before, immediately following and 1, 2, 3, 4, 5 or 6 weeks post injury. RESULTS: Treatment with TP enhanced the recovery of full VFM following crush injury of the RLN compared to controls. There was statistically significant improvement in VFM seen at the 1 and 2 week time points (p < 0.05). By 4 weeks TP-treated rats displayed a 100% recovery of VFM function, compared to only 50% by the control group. CONCLUSIONS: TP enhances RLN functional recovery following a crush injury, which further supports its potential general applicability as a therapeutic agent in peripheral nerve injury.


Assuntos
Androgênios/uso terapêutico , Nervos Laríngeos/fisiologia , Regeneração Nervosa/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos do Nervo Laríngeo Recorrente/tratamento farmacológico , Propionato de Testosterona/uso terapêutico , Androgênios/farmacologia , Animais , Nervos Laríngeos/efeitos dos fármacos , Masculino , Regeneração Nervosa/fisiologia , Ratos , Ratos Sprague-Dawley , Traumatismos do Nervo Laríngeo Recorrente/fisiopatologia , Propionato de Testosterona/farmacologia
9.
Cochrane Database Syst Rev ; (12): CD008240, 2011 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-22161424

RESUMO

BACKGROUND: Lichen sclerosus is a chronic, inflammatory skin condition that most commonly occurs in adult women, although it may also be seen in men and children. It primarily affects the genital area and around the anus, where it causes persistent itching and soreness. Scarring after inflammation may lead to severe damage by fusion of the vulval lips (labia); narrowing of the vaginal opening; and burying of the clitoris in women and girls, as well as tightening of the foreskin in men and boys, if treatments are not started early. Affected people have an increased risk of genital cancers. OBJECTIVES: To assess the effects of topical interventions for genital lichen sclerosus and adverse effects reported in included trials. SEARCH METHODS: We searched the following databases up to 16 September 2011: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE (from 2005), EMBASE (from 2007), LILACS (from 1982), CINAHL (from 1981), British Nursing Index and Archive (from 1985), Science Citation Index Expanded (from 1945), BIOSIS Previews (from 1926), Conference Papers Index (from 1982), and Conference Proceedings Citation Index - Science (from 1990). We also searched ongoing trial registries and scanned the bibliographies of included studies, published reviews, and papers that had cited the included studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) of topical interventions in genital lichen sclerosus. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, extracted data, and assessed the risk of bias. A third author was available for resolving differences of opinion. MAIN RESULTS: We included 7 RCTs, with a total of 249 participants, covering 6 treatments. Six of these RCTs tested the efficacy of one active intervention against placebo or another active intervention, while the other trial tested three active interventions against placebo.When compared to placebo in one trial, clobetasol propionate 0.05% was effective in treating genital lichen sclerosus in relation to the following outcomes: 'participant-rated improvement or remission of symptoms' (risk ratio (RR) 2.85, 95% confidence interval (CI) 1.45 to 5.61) and 'investigator-rated global degree of improvement' (standardised mean difference (SMD) 5.74, 95% CI 4.26 to 7.23).When mometasone furoate 0.05% was compared to placebo in another trial, there was a significant improvement in the 'investigator-rated change in clinical grade of phimosis' (SMD -1.04, 95% CI -1.77 to -0.31).Both trials found no significant differences in reported adverse drug reactions between the corticosteroid and placebo groups. The data from four trials found no significant benefit for topical testosterone, dihydrotestosterone, and progesterone. When used as maintenance therapy after an initial treatment with topical clobetasol propionate in another trial, topical testosterone worsened the symptoms (P < 0.05), but the placebo did not.One trial found no differences between pimecrolimus and clobetasol propionate in relieving symptoms through change in pruritus (itching) (SMD -0.33, 95% CI -0.99 to 0.33) and burning/pain (SMD 0.03, 95% CI -0.62 to 0.69). However, pimecrolimus was less effective than clobetasol propionate with regard to the 'investigator-rated global degree of improvement' (SMD -1.64, 95% CI -2.40 to -0.87). This trial found no significant differences in reported adverse drug reactions between the pimecrolimus and placebo groups. AUTHORS' CONCLUSIONS: The current limited evidence demonstrates the efficacy of clobetasol propionate, mometasone furoate, and pimecrolimus in treating genital lichen sclerosus. Further RCTs are needed to determine the optimal potency and regimen of topical corticosteroids, examine other topical interventions, assess the duration of remission or prevention of flares, evaluate the reduction in the risk of genital squamous cell carcinoma or genital intraepithelial neoplasia, and examine the efficacy in improving the quality of the sex lives of people with this condition.


Assuntos
Anti-Inflamatórios/uso terapêutico , Fármacos Dermatológicos/uso terapêutico , Doenças dos Genitais Masculinos/tratamento farmacológico , Líquen Escleroso e Atrófico/tratamento farmacológico , Líquen Escleroso Vulvar/tratamento farmacológico , Adulto , Criança , Clobetasol/uso terapêutico , Di-Hidrotestosterona/uso terapêutico , Feminino , Humanos , Masculino , Furoato de Mometasona , Pregnadienodiois/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Tacrolimo/análogos & derivados , Tacrolimo/uso terapêutico , Propionato de Testosterona/uso terapêutico
10.
Hemoglobin ; 35(5-6): 659-64, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-22074126

RESUMO

Growth and pubertal disturbances are the most common causes of morbidity, affecting 60-80% ß-thalassemia major (ß-TM) patients worldwide, due mainly to hypogonadotrophic hypogonadism (HH). We undertook a 6-year prospective study of 55 Indian ß-TM children with stunted growth and absent or arrested puberty, aged 15-18 years with pulsatile HH, to evaluate the role of low dose sex steroid priming (6-12 months) for physiological induction of puberty. Eighty percent responded favorably with increase in height, growth spurt and completed pubertal maturation [Tanner stage 4-5 (T4-T5)] and 20% moved from T2 to T3. There was biochemical improvement in maturation of hypothalamic-pituitary (H-P) axis. Those younger than 15 years with minimal iron load had the best outcome. Our data suggest that sex steroid priming is a feasible method of induction of physiological puberty in ß-TM patients with sexual infantilism and reversible apulsatile HH, especially in younger patients with minimal iron loads.


Assuntos
Etinilestradiol/uso terapêutico , Hipogonadismo/complicações , Hipogonadismo/tratamento farmacológico , Puberdade Tardia/tratamento farmacológico , Puberdade Tardia/etiologia , Propionato de Testosterona/uso terapêutico , Talassemia beta/complicações , Adolescente , Etinilestradiol/administração & dosagem , Humanos , Propionato de Testosterona/administração & dosagem , Resultado do Tratamento
12.
Laryngoscope ; 120(8): 1523-30, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20641084

RESUMO

OBJECTIVES/HYPOTHESIS: To investigate the effects of various combinatorial treatments, consisting of a tapering dose of prednisone (P), a brief period of nerve electrical stimulation (ES), and systemic testosterone propionate (TP) on improving functional recovery following an intratemporal facial nerve crush injury. STUDY DESIGN: Prospective, controlled animal study. METHODS: After a right intratemporal facial nerve crush, adult male Sprague-Dawley rats were divided into the following eight treatment groups: 1) no treatment, 2) P only, 3) ES only, 4) ES + P, 5) TP only, 6) TP + P, 7) ES + TP, and 8) ES + TP + P. For each group n = 4-8. Recovery of the eyeblink reflex and vibrissae orientation and movement were assessed. Changes in peak amplitude and latency of evoked response, in response to facial nerve stimulation, was also recorded weekly. RESULTS: : Brief ES of the proximal nerve stump most effectively accelerated the initiation of functional recovery. Also, ES or TP treatments enhanced recovery of some functional parameters more than P treatment. When administered alone, none of the three treatments improved recovery of complete facial function. Only the combinatorial treatment of ES + TP, regardless of the presence of P, accelerated complete functional recovery and return of normal motor nerve conduction. CONCLUSIONS: Our findings suggest that a combinatorial treatment strategy of using brief ES and TP together promises to be an effective therapeutic intervention for promoting regeneration following facial nerve injury. Administration of P neither augments nor hinders recovery.


Assuntos
Traumatismos do Nervo Facial/terapia , Animais , Terapia Combinada , Modelos Animais de Doenças , Terapia por Estimulação Elétrica , Glucocorticoides/uso terapêutico , Masculino , Fármacos do Sistema Nervoso Periférico/uso terapêutico , Prednisona/uso terapêutico , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Propionato de Testosterona/uso terapêutico
13.
Exp Clin Endocrinol Diabetes ; 118(7): 459-65, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20200810

RESUMO

Diabetes is frequently associated with declining sexual function resulting from oxidative damage. NADPH oxidase is a major resource of reactive oxygen species (ROS) in the testes and is likely related to an activated endothelin-1 (ET-1) system. An activation of NADPH oxidase-ET-1 pathway was hypothesized in diabetic testopathy. We verified the hypothesis and tested if strontium fructose 1,6-diphosphate (FDP-Sr) could relieve these changes in diabetic testis as compared to testosterone propionate (TP) and sildenafil. Diabetes was produced in male Sprague-Dawley rats 8 weeks after a single injection of streptozotocin (STZ), and interventions with testosterone propionate (TP), sildenafil and FDP-Sr were conducted in the last 4 weeks. Blood glucose, testosterone, follicle stimulating hormone (FSH) , luteinizing hormone (LH) and expressions of NADPH oxidase subunits and the ET system were measured. Decreased insulin, FSH, LH and testosterone in serum were found associating with testicular oxidative stress in STZ-injected rats. Additionally, over-expressions of NADPH oxidase p22, p47, p67 subunits and the ET pathway were significant in the diabetic testis relative to normal and were completely abolished by FDP-Sr. Both TP and sildenafil were not beneficial to diabetic testopathy except serum androgen raised by TP. Activated NADPH oxidase and ET system are significant contributing to testis injury and are responded to FDP-Sr only, against both TP and sildenafil, by restoring the testis function and the hypothalamus-pituitary-testis axis. It is due to its extra-energy supply and an antioxidant activity of FDP-Sr.


Assuntos
Diabetes Mellitus Experimental/complicações , Frutosedifosfatos/uso terapêutico , NADPH Oxidases/biossíntese , Doenças Testiculares/tratamento farmacológico , Doenças Testiculares/enzimologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Experimental/induzido quimicamente , Endotelina-1/análise , Hormônio Foliculoestimulante/sangue , Insulina/sangue , Hormônio Luteinizante/sangue , Masculino , Estresse Oxidativo/efeitos dos fármacos , Piperazinas/uso terapêutico , Purinas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Citrato de Sildenafila , Sulfonas/uso terapêutico , Testículo/enzimologia , Testículo/fisiopatologia , Testosterona/sangue , Propionato de Testosterona/uso terapêutico
14.
J Appl Toxicol ; 30(3): 233-41, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19847774

RESUMO

This study investigated the effects of perinatal cadmium exposure on physical and reflexologic development of pup rats. It was examined if the immediate postpartum testosterone administration was able to reverse the toxic effects of the metal. Forty Wistar pregnant rats were divided into three groups: control and 10 and 20 mg kg(-1) per day of cadmium chloride. These dams were treated from gestational days 18 to 21, and until the 7th lactation day. Immediately after birth, half of the offspring from the experimental and control groups received 50 microL of testosterone 0.2% i.p. The maternal body weight gain, food and water consumption were measured during the treatment period. In pups, the body weight, body length, physical landmarks, reflex development and the general activity were assessed. Results showed that: only 20 mg kg(-1) cadmium induced maternal toxicity; pup body weight and body weight gain were reduced in all experimental groups; only the cadmium-exposed offspring not treated with testosterone treatment showed a reduction in body length and body length gain; cadmium highest dose reduced the anogenital index in pups and delayed physical and reflexes development; and cadmium effects on the offspring, except in body length gain, were not reversed by testosterone. The results indicate that perinatal maternal exposure to cadmium promoted changes in the development of male rat offspring, reprogramming the pup's development. Testosterone administration was not able to reverse the cadmium effects, even on those parameters more directly related to the androgenic system as the testis descent and anogenital distance delays.


Assuntos
Cádmio/toxicidade , Efeitos Tardios da Exposição Pré-Natal/prevenção & controle , Substâncias Protetoras/uso terapêutico , Propionato de Testosterona/uso terapêutico , Envelhecimento/efeitos dos fármacos , Animais , Animais Lactentes , Comportamento Animal/efeitos dos fármacos , Tamanho Corporal/efeitos dos fármacos , Cloreto de Cádmio/administração & dosagem , Intoxicação por Cádmio/tratamento farmacológico , Dieta , Relação Dose-Resposta a Droga , Ingestão de Líquidos/efeitos dos fármacos , Feminino , Lactação , Masculino , Exposição Materna/efeitos adversos , Gravidez , Ratos , Ratos Wistar , Reflexo/efeitos dos fármacos , Maturidade Sexual/efeitos dos fármacos
15.
Exp Neurol ; 223(1): 183-91, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-19427307

RESUMO

As functional recovery following peripheral nerve injury is dependent upon successful repair and regeneration, treatments that enhance different regenerative events may be advantageous. Using a rat facial nerve crush axotomy model, our lab has previously investigated the effects of a combinatorial treatment strategy, consisting of electrical stimulation (ES) of the proximal nerve stump and testosterone propionate (TP) administration. Results indicated that the two treatments differentially enhance facial nerve regenerative properties, whereby ES reduced the delay before sprout formation, TP accelerated the overall regeneration rate, and the combinatorial treatment had additive effects. To delineate the molecular mechanisms underlying such treatments, the present study investigated the effects of ES and TP on expression of specific regeneration-associated genes. Following a right facial nerve crush at the stylomastoid foramen, gonadectomized adult male rats were administered only ES, only TP, a combination of both, or left untreated. Real time RT-PCR analysis was used to assess fold changes in mRNA levels in the facial motor nucleus at 0 h, 6 h, 1 d, 2 d, 7 d, and 21 d post-axotomy. The candidate genes analyzed included two tubulin isoforms (alpha(1)-tubulin and beta(II)-tubulin), 43-kiloDalton growth-associated protein (GAP-43), brain derived neurotrophic factor (BDNF), pituitary adenylate cyclase-activating peptide (PACAP), and neuritin (candidate plasticity-related gene 15). The two treatments have differential effects on gene expression, with ES leading to early but transient upregulation and TP producing late but steady increases in mRNA levels. In comparison to individual treatments, the combinatorial treatment strategy has the most enhanced effects on the transcriptional program activated following injury.


Assuntos
Androgênios/uso terapêutico , Estimulação Elétrica/métodos , Doenças do Nervo Facial/terapia , Regulação da Expressão Gênica/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Propionato de Testosterona/uso terapêutico , Análise de Variância , Animais , Axotomia/métodos , Fator Neurotrófico Derivado do Encéfalo/genética , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Modelos Animais de Doenças , Proteína GAP-43/genética , Proteína GAP-43/metabolismo , Masculino , Regeneração Nervosa/fisiologia , Neurite (Inflamação)/genética , Neurite (Inflamação)/metabolismo , Orquiectomia/métodos , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/genética , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de Tempo , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo
16.
Restor Neurol Neurosci ; 27(6): 633-44, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20042787

RESUMO

PURPOSE: The neurotherapeutic effects of nerve electrical stimulation and gonadal steroids have independently been demonstrated. The purpose of this study was to investigate the therapeutic potential of a combinatorial treatment strategy of electrical stimulation and gonadal steroids on peripheral nerve regeneration. METHODS: Following a facial nerve crush axotomy in gonadectomized adult male rats, testosterone propionate (TP), dihydrotestosterone (DHT), or estradiol (E(2)) was systemically administered with/without daily electrical stimulation of the proximal nerve stump. Facial nerve outgrowth was assessed at 4 and 7 days post-axotomy using radioactive labeling. RESULTS: Administration of electrical stimulation alone reduced the estimated delay in sprout formation but failed to accelerate the overall regeneration rate. Conversely, TP treatment alone accelerated the regeneration rate by approximately 10% but had no effect on the sprouting delay. Combining TP with electrical stimulation, however, maintained the enhanced rate and reduced the sprouting delay. DHT treatment alone failed to alter the regeneration rate but combining it with electrical stimulation increased the rate by 10%. E(2) treatment alone increased the regeneration rate by approximately 5% but with electrical stimulation, there was no additional effect. CONCLUSIONS: Electrical stimulation and gonadal steroids differentially enhanced regenerative properties. TP, an aromatizable androgen, augmented regeneration most, suggesting a synergism between androgenic and estrogenic effects. Therapeutically, combining electrical stimulation with gonadal steroids may boost regenerative properties more than the use of either treatment alone.


Assuntos
Estimulação Elétrica , Doenças do Nervo Facial/terapia , Regeneração Nervosa/fisiologia , Esteroides/uso terapêutico , Animais , Axotomia/métodos , Di-Hidrotestosterona/farmacologia , Di-Hidrotestosterona/uso terapêutico , Modelos Animais de Doenças , Estradiol/farmacologia , Estradiol/uso terapêutico , Doenças do Nervo Facial/tratamento farmacológico , Leucina , Lisina , Masculino , Regeneração Nervosa/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Esteroides/farmacologia , Propionato de Testosterona/farmacologia , Propionato de Testosterona/uso terapêutico , Fatores de Tempo , Trítio
17.
Otolaryngol Head Neck Surg ; 139(1): 62-7, 2008 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-18585563

RESUMO

OBJECTIVE: We investigated the combined effects of electrical stimulation and testosterone propionate on overall recovery time in rats with extracranial crush injuries to the facial nerve. STUDY DESIGN: Male rats underwent castration 3 to 5 days prior to right facial nerve crush injury and electrode implantation. Rats were randomly assigned to two groups: crush injury + testosterone or crush injury with electrical stimulation + testosterone. Recovery was assessed by daily subjective examination documenting vibrissae orientation/movement, semi-eye blink, and full eye blink. RESULTS: Milestones of early recovery were noted to be significantly earlier in the groups with electrical stimulation, with/without testosterone. The addition of testosterone to electrical stimulation showed significant earlier return of late recovery parameters and complete overall recovery. CONCLUSION: Electrical stimulation may decrease cell death or promote sprouting to accelerate early recovery. Testosterone may affect the actual rate of axonal regeneration and produce acceleration in functional recovery. By targeting different stages of neural regeneration, the synergy of electrical stimulation and testosterone appears to have promise as a neurotherapeutic strategy for facial nerve injury.


Assuntos
Terapia por Estimulação Elétrica , Traumatismos do Nervo Facial/terapia , Propionato de Testosterona/uso terapêutico , Animais , Terapia Combinada , Eletrodos Implantados , Masculino , Ratos , Ratos Sprague-Dawley , Propionato de Testosterona/administração & dosagem , Cicatrização/efeitos dos fármacos , Cicatrização/fisiologia
18.
Zhen Ci Yan Jiu ; 32(4): 229-33, 236, 2007 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-17907383

RESUMO

OBJECTIVE: To observe the effect of mild moxibustion on the reproductive endocrine in rats with partial androgen deficiency (PAD). METHODS: Thirty male SD rats (aged 12 months) were randomized into control, androlin (testosterone propionate) and moxibustion ["Shenshu" (BL 23), "Mingmen" (GV 4) and 'Guanyuan" (CV 4)] groups. PAD was determined by comparing these aging rats (n=50) with young rats (n=30) in serum total testosterone (TT) and free testosterone (FT) contents which were detected with radioimmunoassay. At the end of experiments, the rats' spleen, testis, thymus, and perirenal fat weight were detected respectively for calculating visceral index (each viscera weight/body weight). The rats' tail suspension tests were conducted for calculating the animal immobility duration in 6 mm, and exhaustion swimming tests carried out for analyzing the duration of exhaustion swimming (from placing them into a water pool to the time when the animal sunk into water for 6 s). RESULTS: (1) After the treatment, serum TT and FT contents in moxibustion and androlin groups increased significantly compared with pretherapy in each group (P < 0.01) and compared with control group (P < 0.05, 0.01). (2) Results of rats' tail suspension tests displayed that after the therapy, the duration of immobility in moxibustion and androlin groups decreased markedly in comparison with pre-treatment of each group (P < 0.05) and with control group (androlin group, P < 0.05). (3) Compared with control group, the duration of exhaustion swimming of moxibustion and androlin groups increased considerably (P < 0.01). No significant differences were found between moxibustion and androlin groups in serum TT and FT levels, immobility duration and the duration of exhaustion swimming (P > 0.05). (4) Compared with control group, the indexes of thymus and testis raised remarkably, and that of perirenal fat lowered evidently (P < 0.05, 0.01), while no significant difference was found between moxibustion and androlin groups in indexes of thymus, testis and perirenal fat (P > 0.05). There existed significant correlation between visceral index (thymus, testis and perirenal fat) and serum TT and FT levels respectively (P < 0.01), and between the duration of immobility and exhaustion swimming and serum TT and FT levels separately (P < 0.01). CONCLUSION: Mild moxibustion may prevent blood TT and FT levels from decline, reduce fat accumulation in the abdomen, regulate immune function, improve the depression state and myodynamia in the aging rats, which is comparable to the effects of testosterone propionate.


Assuntos
Androgênios/deficiência , Moxibustão , Testosterona/sangue , Animais , Hipotálamo/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley , Linfócitos T/imunologia , Testículo/fisiopatologia , Propionato de Testosterona/uso terapêutico
19.
Acta Obstet Gynecol Scand ; 86(6): 715-9, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17520405

RESUMO

OBJECTIVE: To evaluate the therapeutic regimens and symptomatic response rates in patients with vulvar lichen sclerosus associated with variable degrees of squamous cell hyperplasia (mixed disease). MATERIAL AND METHODS: Eighty-three women with biopsy-proven vulvar mixed disease were evaluated for this retrospective study. All patients were initially treated with topical fluorinated corticosteroids, and then 2% testosterone propionate in petrolatum or 0.05% clobetasol 17-propionate (44 (53%) versus 39 (47%)). RESULTS: The remission rates were 82 and 93% in the testosterone and clobetasol subgroups at the end of 6 months (p=0.112), respectively. The disease recurred in 8% of the patients. The recurrence rates in the testosterone and clobetasol arms were 13 and 5%, respectively (p=0.163). The histopathological review of the repeat vulvar biopsies of the patients without symptomatic relief revealed 6 (60%) patients with persistent disease, 2 (20%) with lichen sclerosus, 1 (10%) with atypical squamous hyperplasia, and 1 (10%) with VIN1. Two patients with recurrent disease and 2 patients with vulvar intraepithelial neoplasia I-II or atypical squamous hyperplasia were treated with skinning vulvectomy. CONCLUSIONS: Clobetasol resulted in higher remission and lower recurrence rates than those in testosterone therapy, although statistically significant differences were not obtained. In the evaluation of patients without symptomatic relief, the first step should be a vulvar biopsy to exclude the presence of atypical components.


Assuntos
Clobetasol/uso terapêutico , Glucocorticoides/uso terapêutico , Propionato de Testosterona/uso terapêutico , Líquen Escleroso Vulvar/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hiperplasia/tratamento farmacológico , Hiperplasia/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Prevenção Secundária , Líquen Escleroso Vulvar/patologia
20.
Int J Gynaecol Obstet ; 96(2): 117-21, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17239881

RESUMO

OBJECTIVE: To compare the effects of topical testosterone and clobetasol treatments on symptoms remission and recurrence rates in patients with vulvar lichen sclerosus (LS). METHODS: A retrospective review of the records showed that, of 140 patients with biopsy-proven vulvar LS, 80 were treated with applications of testosterone propionate 2% in petrolatum and 60 with clobetasol 17-propionate 0.05%. RESULTS: The response rates after 6 months were 77.5% for patients treated with testosterone and 91.7% for those treated with clobetasol (P=0.02). The recurrence rates were 20% and 6.7% in the 2 groups, respectively (P=0.02). Premenopausal patients had higher remission rates and lower recurrence rates than postmenopausal patients (P>0.05). Considering whole patients, low remission rates and high recurrence rates were observed in patients who had had a hysterectomy (P>0.05). CONCLUSION: Treatment of LS with a corticosteroid provided excellent remission rates. In this study, clobetasol 17-propionate 0.05% was superior to testosterone for both remission induction and maintenance therapy.


Assuntos
Androgênios/uso terapêutico , Clobetasol/uso terapêutico , Glucocorticoides/uso terapêutico , Propionato de Testosterona/uso terapêutico , Líquen Escleroso Vulvar/tratamento farmacológico , Administração Tópica , Adulto , Androgênios/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Propionato de Testosterona/administração & dosagem
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