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Parathyroid carcinoma (PC) is a very rare head-neck malignancy. Because the symptoms of parathyroid carcinoma are similar to those of benign causes of hyperparathyroidism, it may be not easy to detect it before surgery. The management of PC after initial surgery will be perplexing because of the adequacy of surgery. We wish to describe the difficulties encountered throughout treatment using a literature review. We conducted a retrospective analysis of individuals with parathyroid carcinoma who had treatment at our department between 2017 and 2022. We gathered data on the clinical profile, investigations, management of hypercalcemia, surgical techniques, histopathological features, adjuvant therapy, and outcomes. We treated three patients with parathyroid carcinoma: Two patients with inferior parathyroid carcinoma and one with superior parathyroid carcinoma. Generalized weakness and bony pain are the predominant symptoms. In all cases, the tumor was located using 99Tc MIBI / SPECT scintigraphy and Ultrasonography. Hemithyroidectomy and tumor excision were done as the surgery of choice. All are disease-free at the 12th-month follow-up. We suggested that parathyroid hormone testing be performed in all bony fibrous lesions to rule out hyperparathyroidism. PC is a likely diagnosis when there is noticeable throat swelling, elevated PTH levels greater than 400 IU/L, and serum calcium levels greater than 15 mg/dL.
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Indian basil (Ocimum basillicum), lemongrass (Cymbopogon flexuosus) and coriander (Coriandrum sativum) leaves are a good source of aromatic oils; however, their extraction volume is low. Hence, two pre-treatment systems (ohmic-heating and ultrasonic) were devised for extraction of essential oils (EO) from the leaves of these three plant spp., which consequently enhanced the EO yield and saved the time and energy. First of all, an experimental set-up was developed for ohmic-heating pre-treatment which was subjected to the optimization of electric conductivity of lemongrass and coriander leaves at 26.25 V/cm and for Indian basil at 22.5 V/cm voltage gradient. An Experimental setup was also developed for ohmic heating-assisted hydro-distillation (OHD). Finally, conventional Clevenger hydro-distillation (CHD), OHD, ultrasonic-assisted conventional hydro-distillation (UACHD) and ultrasonic-assisted ohmic-heating hydro-distillation (UAOHD) methods were evaluated for their effectiveness in the extraction of the EOs. The OHD took 3.5 h time with 410 W power consumption compared to 5 h time and 500 W power consumption in CHD of sleeted leaves. Likewise, a saving of ~ 86% in time and 74% in energy consumption was observed for EO extraction through UAOHD over CHD. Quantity of EOs extracted from all three aromatic plant spp. leaves followed the trend of UAOHD > UACHD > OHD > CHD methods, respectively. Overall, ultrasonic pre-treatment coupled with ohmic-heating assisted hydro-distillation (UAOHD) proved as an innovative and effective clean EO extraction technology which took shorter extraction time and lesser energy consumption with better EO yield over the UACHD, OHD and CHD methods from the leaves of Indian basil, lemongrass and coriander.
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Coriandrum , Cymbopogon , Ocimum basilicum , Óleos Voláteis , Ultrassom , Calefação , Folhas de PlantaRESUMO
OBJECTIVES: West syndrome is a severe epileptic encephalopathy of young age. It is characterized by a clinico-electrical triad of infantile epileptic spasms, regression or arrest of psychomotor development, and hypsarrhythmia. In the last two decades, the large progress in the development of newer antiepileptic drugs has allowed us to have a vast choice of treatment options to control spasms, although they often fail to do so. Thus, there is a need to explore other treatment options. MATERIALS & METHODS: Subjects in this open-labelled randomized control trial were included newly diagnosed children of age between 3 months and 5 years of both genders. A total of 52 children were recruited and randomized into two groups: an intervention group (n=30) and a non-intervention group (n=22). Magnesium sulphate was provided for the intervention group but not for the non-intervention one. Both groups received the rest of the treatments, including adrenocorticotropic hormone and antiepileptic drugs. The follow-up period was three months, at the end of which a per-protocol analysis was performed. RESULTS: There was no significant difference in seizure control and neurodevelopmental outcome between both groups, but electroencephalogram significantly improved in the intervention group compared to the control. Also, the clinical response was better in patients with normal initial serum magnesium levels in the intervention group (p=0.003) than in other patients. CONCLUSION: Magnesium supplementation may be helpful in children with West syndrome.
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We aimed to compare surgical, oncological, and functional outcomes of robot-assisted radical prostatectomy (RARP) in prostate cancer patients with and without prior history of transurethral resection of the prostate (TURP), using a matched cohort analysis. In an IRB-approved protocol, all patients who underwent RARP at our institution between April 2005 and July 2018 with at least 1-year follow-up were included. Among these, patients who had undergone a previous TURP (Group A) were compared with those without TURP (Group B) using the Survival, Continence, and Potency outcomes reporting system. Using propensity score matching for age, PSA and Gleason score, the two cohorts were further subdivided in a 1:2 ratio into Group C (prior TURP from Group A) and Group D (without prior TURP from Group B). Similar comparisons were made between Group C and D. Patients in Group A (n = 40) had lower PSA (p = 0.031) and were more likely to have Gleason grade 1 disease (p = 0.035) than patients in Group B (n = 143). In the propensity-matched group analysis, patients of Group C (n = 38) had higher operative time and blood loss than Group D (n = 76) patients. Group C patients also had lower continence at 3, 6, and 12 months after surgery. However, oncological and potency outcomes were similar in both the groups. We concluded that previous TURP is a predictor for surgical and continence outcomes following RARP. Even though these patients have a potentially lower stage or grade of disease, they are less likely to achieve social continence than men who have not had a previous TURP. This information would be important in counseling them for treatment options.
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Neoplasias da Próstata , Procedimentos Cirúrgicos Robóticos , Robótica , Ressecção Transuretral da Próstata , Estudos de Coortes , Humanos , Masculino , Antígeno Prostático Específico , Prostatectomia/métodos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Ressecção Transuretral da Próstata/métodos , Resultado do TratamentoRESUMO
OBJECTIVE: To study the effect of 3 antioxidants viz. selenium, carnitine and coenzyme Q10, alone or in combination, on both semen parameters and pregnancy rates in couples with male factor infertility. METHODS: Using PRISMA guidelines, a systematic search was performed of the PubMed, Scopus, EMBASE, and Web of Science databases for randomized studies comparing selenium, carnitine or coenzyme Q10 with placebo in the treatment of male infertility and reporting semen and pregnancy outcomes. RESULTS: A total of 3304 studies were screened of which 20 were included. The study protocol was registered with PROSPERO (CRD42020210284). Pregnancy rate in the treatment group (69/426, 16.2%) was not different from the placebo (45/401, 11.2%) (Pâ¯=â¯.05). Treatment group showed higher motility [mean difference 5.05, 95% CI (2.77, 7.34), P =<.0001], progressive motility [mean difference 5.72, 95% CI (2.77, 8.66), Pâ¯=â¯.0001], sperm concentration [mean difference 6.58, 95% CI (3.22, 9.93), Pâ¯=â¯.0001] than placebo. CONCLUSION: Although antioxidants and their combinations are associated with improvement in sperm concentration, motility, and semen volume, the differences are small. There is no difference in pregnancy rates between patients receiving selenium, carnitine, and coenzyme Q10, or placebo. The quality of studies is poor, limiting the level of evidence.
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Infertilidade Masculina , Selênio , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Carnitina/farmacologia , Carnitina/uso terapêutico , Feminino , Humanos , Infertilidade Masculina/tratamento farmacológico , Masculino , Gravidez , Selênio/farmacologia , Selênio/uso terapêutico , Sêmen , Motilidade dos Espermatozoides , Espermatozoides , Ubiquinona/análogos & derivadosRESUMO
Highlights: This prospective study is one of the largest clinical trials in essential tremor to date. Study findings suggest that individualized non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction and improves quality of life for many essential tremor patients. Background: Two previous randomized, controlled, single-session trials demonstrated efficacy of non-invasive neuromodulation therapy targeting the median and radial nerves for reducing hand tremor. This current study evaluated efficacy and safety of the therapy over three months of repeated home use. Methods: This was a prospective, open-label, post-clearance, single-arm study with 263 patients enrolled across 26 sites. Patients were instructed to use the therapy twice daily for three months. Pre-specified co-primary endpoints were improvements on clinician-rated Tremor Research Group Essential Tremor Rating Assessment Scale (TETRAS) and patient-rated Bain & Findley Activities of Daily Living (BF-ADL) dominant hand scores. Other endpoints included improvement in the tremor power detected by an accelerometer on the therapeutic device, Clinical and Patient Global Impression scores (CGI-I, PGI-I), and Quality of Life in Essential Tremor (QUEST) survey. Results: 205 patients completed the study. The co-primary endpoints were met (pâª0.0001), with 62% (TETRAS) and 68% (BF-ADL) of 'severe' or 'moderate' patients improving to 'mild' or 'slight'. Clinicians (CGI-I) reported improvement in 68% of patients, 60% (PGI-I) of patients reported improvement, and QUEST improved (p = 0.0019). Wrist-worn accelerometer recordings before and after 21,806 therapy sessions showed that 92% of patients improved, and 54% of patients experienced ≥50% improvement in tremor power. Device-related adverse events (e.g., wrist discomfort, skin irritation, pain) occurred in 18% of patients. No device-related serious adverse events were reported. Discussion: This study suggests that non-invasive neuromodulation therapy used repeatedly at home over three months results in safe and effective hand tremor reduction in many essential tremor patients.
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Terapia por Estimulação Elétrica , Tremor Essencial/terapia , Mãos , Nervo Mediano , Avaliação de Resultados em Cuidados de Saúde , Nervo Radial , Adulto , Idoso , Idoso de 80 Anos ou mais , Terapia por Estimulação Elétrica/efeitos adversos , Terapia por Estimulação Elétrica/instrumentação , Terapia por Estimulação Elétrica/métodos , Tremor Essencial/fisiopatologia , Feminino , Mãos/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto JovemRESUMO
A majority of the cases of primary male infertility are idiopathic with the underlying molecular mechanisms contributing to the pathophysiology as yet unknown. Effects of the environment can alter the sperm epigenome thereby impacting male reproductive health. Epigenetic mechanisms are crucial to understanding health and disease, and methylome alterations are now known to have far-reaching clinical implications. Here, we report the results from our pilot study, a first of its kind analysis of the effect of the traditional practice of yoga on human sperm quality. We find marked improvement in sperm characteristics in patients of idiopathic male infertility following a supervised 21-day yoga regimen. Furthermore, next-generation sequencing-based methylome analysis reveals alterations in the sperm epigenome of these patients. We find that the practice of yoga is associated with DNA methylation changes at nearly 400 genes, 147 of which were hypermethylated while 229 were hypomethylated. These included promoters of several genes linked to maintenance of fertility and genomic integrity. This novel piece of work draws a direct link between positive lifestyle practices and male reproductive health.
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Epigenoma , Infertilidade Masculina/metabolismo , Infertilidade Masculina/terapia , Espermatozoides/metabolismo , Yoga , Adulto , Humanos , Masculino , Projetos PilotoRESUMO
In today's world, nanotechnology is reaching practically every ground and entering the human lifestyle by becoming a part of it. Thus, it is vital to check the cytotoxic and genotoxic effects of nanosubstances on plants, as they are the base constituent of ecosystem. The present work deals with the toxicity evaluation of metallosurfactant derived palladium oxide nanoparticles towards Allium sativum (Garlic cloves). The nanoparticles were prepared using microemulsion quenching method (a softer approach) using palladium metallosurfactants as precursors. The three ligands used were cetyltrimethylammonium chloride (CTAC), dodecylamine (DDA) and hexadecylamine (HEXA). Further, their characterization was done using TEM, Size Distribution curve, FESEM, EDS, XRD and Zeta potential. Garlic (Allium sativum) cloves were used to investigate the cytotoxicity and genotoxicity of fabricated PdO NPs. To check the cytotoxicity, optical microscopy was employed and for the genotoxic assessment, different parameters such as chromosomal aberrations in the mitosis, circular dichroism, and gel electrophoresis were utilized. From mitosis study, chromosomes aberrations were confirmed such as chromosomes stickiness, breakage, C-Mitosis, delay in anaphase, spindle fibre abnormality, laggard, vagrant and condensed chromosomes. Morphology of A. sativum clove, rooting and shooting pattern in the presence of PdO nanosuspension was observed. From all the experiments, it was concluded that all the three PdO nanosuspension are toxic in nature to both the cells and to genome, although, bishexadecyltrimethyl ammonium palladium tetrachloride (PdCTAC) Ns was found to be the most cytotoxic and genotoxic. Gel electrophoresis also confirmed the complete degradation of DNA in the presence of PdCTAC Ns.
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Aberrações Cromossômicas , Dano ao DNA/efeitos dos fármacos , Alho/efeitos dos fármacos , Nanopartículas/toxicidade , Paládio/toxicidade , Aminas/química , Cetrimônio/química , Dicroísmo Circular , Hidrocarbonetos/química , Ligantes , Microscopia Eletrônica de Transmissão , Mitose/efeitos dos fármacos , Testes de Mutagenicidade , Nanopartículas/química , Paládio/química , Tamanho da Partícula , Raízes de Plantas/efeitos dos fármacos , Brotos de Planta/efeitos dos fármacosRESUMO
The attention of current work was on the fabrication of effective nanoadsorbent of hydroxyapatite (HAp) for the controlled release of atrazine (ATZ) formulation. The ATZ-HAp complex (ATZ@HAp) was able to inhibit the growth of Brassica sp. under in situ conditions. This developed methodology aspires to cease the agricultural runoffs of ATZ applied with the HAp adjuvant and ensure their effective functioning. The efficacy of the protocol was mainly accomplished by adsorbing ATZ over the surface of HAp NPs that restricted its premature runoff and promoted the prolonged herbicidal efficiency. The influence of fundamental parameters i.e., HAp dose, ATZ dose and initial pH on the adsorption process was investigated systematically. The suitability of ATZ@HAp complex for real world application was adjudged after proofing its toxicological behaviour and its role in Zea mays plantations. The complex was found to be non-toxic and nurturing due to its phosphate rich nature. Further investigations of ATZ@HAp complex and its effect on the non-target species will help in establishing an effective framework for their commercial use in agricultural practices.
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Agricultura/métodos , Atrazina/administração & dosagem , Durapatita/química , Herbicidas/administração & dosagem , Nanoestruturas/química , Poluição Química da Água/prevenção & controle , Adsorção , Poluentes Químicos da Água/análise , Zea maysRESUMO
The utilization of selenium nanomaterials (Se Nps) in material and biological science is quickly growing, crafting an imperative need for toxicological evaluation of the exposure prospective and environmental consequences of Se Nps. The combination of quantitative multi-assay approach into environmental toxicological analysis has provided novel opportunities to build up effective markers and scrutinize the means of venomous nature of Se Nps in the current study. In the present work, we analyzed the toxicological effect of bare and surface functionalized Se Nps by using multi assay viz. seed germination studies as a function of concentration of SeNps and by using antifungal assays. The influence of SeNps on bacterial activities were also investigated by using the S. aureus, E. coli, P. aeruginosa and S. typhi bacterial strains as widespread marker species for antibacterial studies. The ocular assessment of chlorophyll content was maximum for Brij coated Se NPs (98%) as compared to bare (20%), SDS (45%) and CTAB (38%) coated SeNps. The existence of chromosomal aberrations in root meristems of A. cepa(A. cepa) with computed MI values of 16, 25, 33 and 52% for bare, CTAB, SDS and Brij coated particles has indicated the genotoxic effects of SeNps. The biocompatible nature of Brij coated Se Nps was observed from the faster mobility of DNA in gel electrophoresis studies. The investigational studies in the current work appraise the toxicity and measure the competence of obtained data to characterize possibilities of probable threats, prominence of data requirement and breaches that must be filled to diminish the ambiguities about the safe use of Se Nps.
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Nanopartículas/toxicidade , Selênio/toxicidade , Testes de Toxicidade , Escherichia coli , Estudos Prospectivos , Staphylococcus aureus , TensoativosRESUMO
OBJECTIVE: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. METHODS: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months. The primary outcome variable was the change from baseline to month 60 in Total Functional Capacity score (for patients who survived) combined with time to death (for patients who died) analyzed using a joint-rank analysis approach. RESULTS: An interim analysis for futility revealed a conditional power of <5% for the primary analysis, prompting premature conclusion in July 2014. No statistically significant differences were seen between treatment groups for the primary or secondary outcome measures. CoQ was generally safe and well-tolerated throughout the study. CONCLUSIONS: These data do not justify use of CoQ as a treatment to slow functional decline in HD. CLINICALTRIALSGOV IDENTIFIER: NCT00608881. CLASSIFICATION OF EVIDENCE: This article provides Class I evidence that CoQ does not slow the progressive functional decline of patients with HD.
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Doença de Huntington/tratamento farmacológico , Ubiquinona/análogos & derivados , Vitaminas/uso terapêutico , Adulto , Austrália , Canadá , Método Duplo-Cego , Feminino , Humanos , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento , Ubiquinona/uso terapêutico , Estados UnidosRESUMO
Emblica officinalis Gaertn. belonging to family Euphorbiaceae is commonly known as Indian gooseberry or "Amla" in India. It is used as a 'rejuvenating herb' in traditional system of Indian medicine. It has been shown to possess antioxidant, anti-inflammatory and anti-apoptotic effects. Thus, on the basis of its biological effects, the present study was undertaken to evaluate the protective effect of the dried fruit extract of the E. Officinalis (EO) in cisplatin-induced nephrotoxicity in rats and also to evaluate the mechanism of its nephroprotection. The study was done on male albino Wistar rats. They were divided into six groups (n = 6) viz. control, cisplatin-control, cisplatin and EO (150, 300, and 600 mg/kg; p.o. respectively in different groups) and EO only (600 mg/kg; p.o. only). EO was administered orally to the rats for a period of 10 days and on the 7th day, a single injection of cisplatin (8 mg/kg; i.p.) was administered to the cisplatin-control and EO treatment groups. The rats were sacrificed on the 10th day. Cisplatin-control rats had deranged renal function parameters and the kidney histology confirmed the presence of acute tubular necrosis. Furthermore, there were increased oxidative stress, apoptosis and inflammation along with higher expression of MAPK pathway proteins in the rat kidney from the cisplatin-control group. Contrary to this, EO (600 mg/kg) significantly normalized renal function, bolstered antioxidant status and ameliorated histological alterations. The inflammation and apoptosis were markedly lower in comparison to cisplatin-control rats. Furthermore, EO (600 mg/kg) inhibited MAPK phosphorylation which was instrumental in preserving renal function and morphology. In conclusion, the results of our study demonstrated that EO attenuated cisplatin-induced nephrotoxicity in rats through suppression of MAPK induced inflammation and apoptosis.
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BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a common cancer in the north east of India. The present study concerned the prevalence of human papilloma virus (HPV) in the ESCC in north eastern India and its impact on response to chemotherapy. MATERIALS AND METHODS: p16 expression, a surrogate marker for HPV infection was assessed in 101 pre-treatment biopsies of locally advanced ESCC, reported from a comprehensive cancer centre in north east India, using immunohistochemistry. All patients received neo-adjuvant chemotherapy. Response was assessed clinically and histopathologically with attention to p16 expression. RESULTS: p16 was expressed in 22% of ESCC (22 out of 101) and was more prevalent in patients who were more than 45 years of age (P=0.048). p16 positive tumors appeared more commonly in the upper 2/3 of the thoracic esophagus (18 in 22). Nine of the 22 (41%) p16 positive tumors achieved pathologic complete response following neo-adjuvant chemotherapy (P=0.008). There was a trend towards reduced mortality in this group (P=0.048). Some 9 of the 20 (45%) patients who achieved pathologic complete response were p16 positive. CONCLUSIONS: Expression of p16 in ESCC correlates with higher rate of pathologic complete remission in patients undergoing neo adjuvant chemotherapy and could be a predictive marker for response assessment.
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Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Esofágicas/química , Neoplasias Esofágicas/tratamento farmacológico , Proteínas de Neoplasias/análise , Infecções por Papillomavirus/epidemiologia , Adulto , Fatores Etários , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/patologia , Quimioterapia Adjuvante , Inibidor p16 de Quinase Dependente de Ciclina , Neoplasias Esofágicas/patologia , Feminino , Humanos , Índia/epidemiologia , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Infecções por Papillomavirus/metabolismo , Valor Preditivo dos Testes , Prevalência , Indução de Remissão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Note: This editorial is being published simultaneously in the Indian Heart Journal, Indian Journal of Anaesthesia, Indian Journal of Gastroenterology, Indian Journal of Medical Ethics, Indian Journal of Medical Microbiology, Indian Journal of Occupational and Environmental Medicine, Indian Journal of Pathology and Microbiology, Indian Journal of Pharmacology, Indian Journal of Physiology and Pharmacology, Indian Journal of Urology, Indian Pediatrics, International Journal of Health Research & Medicolegal Practice, Journal of Anaesthesiology Clinical Pharmacology, Journal of Ayurveda and Integrative Medicine, Journal of Clinical and Scientific Research, Journal of Conservative Dentistry, Journal of Family Medicine and Primary Care, Journal of Indian Academy of Forensic Medicine, Journal of Mahatma Gandhi Institute of Medical Sciences, Journal of Postgraduate Medicine, National Journal of Integrated Research in Medicine, and The National Medical Journal of India. It may also be published in forthcoming issues of other journals. This editorial is not endorsed by all members of the Indian Association of Medical Journal Editors (IAMJE).
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IMPORTANCE: Coenzyme Q10 (CoQ10), an antioxidant that supports mitochondrial function, has been shown in preclinical Parkinson disease (PD) models to reduce the loss of dopamine neurons, and was safe and well tolerated in early-phase human studies. A previous phase II study suggested possible clinical benefit. OBJECTIVE: To examine whether CoQ10 could slow disease progression in early PD. DESIGN, SETTING, AND PARTICIPANTS: A phase III randomized, placebo-controlled, double-blind clinical trial at 67 North American sites consisting of participants 30 years of age or older who received a diagnosis of PD within 5 years and who had the following inclusion criteria: the presence of a rest tremor, bradykinesia, and rigidity; a modified Hoehn and Yahr stage of 2.5 or less; and no anticipated need for dopaminergic therapy within 3 months. Exclusion criteria included the use of any PD medication within 60 days, the use of any symptomatic PD medication for more than 90 days, atypical or drug-induced parkinsonism, a Unified Parkinson's Disease Rating Scale (UPDRS) rest tremor score of 3 or greater for any limb, a Mini-Mental State Examination score of 25 or less, a history of stroke, the use of certain supplements, and substantial recent exposure to CoQ10. Of 696 participants screened, 78 were found to be ineligible, and 18 declined participation. INTERVENTIONS: The remaining 600 participants were randomly assigned to receive placebo, 1200 mg/d of CoQ10, or 2400 mg/d of CoQ10; all participants received 1200 IU/d of vitamin E. MAIN OUTCOMES AND MEASURES: Participants were observed for 16 months or until a disability requiring dopaminergic treatment. The prospectively defined primary outcome measure was the change in total UPDRS score (Parts I-III) from baseline to final visit. The study was powered to detect a 3-point difference between an active treatment and placebo. RESULTS: The baseline characteristics of the participants were well balanced, the mean age was 62.5 years, 66% of participants were male, and the mean baseline total UPDRS score was 22.7. A total of 267 participants required treatment (94 received placebo, 87 received 1200 mg/d of CoQ10, and 86 received 2400 mg/d of CoQ10), and 65 participants (29 who received placebo, 19 who received 1200 mg/d of CoQ10, and 17 who received 2400 mg/d of CoQ10) withdrew prematurely. Treatments were well tolerated with no safety concerns. The study was terminated after a prespecified futility criterion was reached. At study termination, both active treatment groups showed slight adverse trends relative to placebo. Adjusted mean changes (worsening) in total UPDRS scores from baseline to final visit were 6.9 points (placebo), 7.5 points (1200 mg/d of CoQ10; P = .49 relative to placebo), and 8.0 points (2400 mg/d of CoQ10; P = .21 relative to placebo). CONCLUSIONS AND RELEVANCE: Coenzyme Q10 was safe and well tolerated in this population, but showed no evidence of clinical benefit. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00740714.
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Antioxidantes/administração & dosagem , Doença de Parkinson/diagnóstico , Doença de Parkinson/tratamento farmacológico , Ubiquinona/análogos & derivados , Idoso , Antioxidantes/metabolismo , Relação Dose-Resposta a Droga , Método Duplo-Cego , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/enzimologia , Estudos Prospectivos , Resultado do Tratamento , Ubiquinona/administração & dosagem , Ubiquinona/sangueRESUMO
Fruit extract of Cupressus sempervirens (CS), which is used traditionally to treat Benign Prostatic Hyperplasia (BPH)-like urinary symptoms in patients, was scientifically validated for anti-BPH activity. The ethanolic fruit extract of CS inhibited proliferation of human BPH-stromal cells and the activity was localized to its chloroform-soluble, diterpene-rich fraction. Eight major diterpenes isolated from this fraction exhibited moderate to potent activity and the most active diterpene (labda-8(17),12,14-trien-19-oic acid) exhibited an IC50 of 37.5 µM (antiproliferative activity against human BPH-stromal cells). It significantly inhibited activation (phosphorylation) of Stat-3 in BPH-stromal cells and prevented transactivation of androgen sensitive KLK3/PSA and TMPRSS2 genes in LNCaP cells. Labda-8(17),12,14-trien-19-oic acid-rich CS fraction prevented prostatic hyperplasia in rat model and caused TUNEL labeling of stromal cells with lower expressions of IGF-I, TGF-ß and PCNA, and bcl-2/bax ratio. Human BPH tissues exhibited precise lowering of stromal component after incubation in labda-8(17),12,14-trien-19-oic acid, ex vivo. We conclude that labda-8(17),12,14-trien-19-oic acid contained in CS exhibits anti-BPH activity through inhibition of stromal proliferation and suppression of androgen action in the prostate, presenting a unique lead structure for further optimization of anti-BPH activity.
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Androgênios/metabolismo , Cupressus/química , Diterpenos/farmacologia , Hiperplasia Prostática/tratamento farmacológico , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Frutas/química , Humanos , Masculino , Fosforilação , Ratos , Ratos Sprague-Dawley , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismoRESUMO
OBJECTIVE: Dimension-specific objective measures are criticized for their limited perspective and failure to endorse subjective perceptions by respondents, but the validity and correlates of a subjective global measure of successful aging (SA) are still not well established. We evaluated the reliability and validity of a self-rated analogue scale of global SA in an elderly Singaporean population. DESIGN: Cross-sectional data analysis using a comprehensive questionnaire survey. PARTICIPANTS AND SETTING: 489 community-dwelling Singaporeans aged 65 years and over. MEASUREMENTS: Self-rated SA on an analogue scale from 1 (least successful) to 10 (most successful) was analyzed for its relationship to criterion-based measures of five specific dimensions (physical health and function, mental well-being, social engagement, psychological well-being, and spirituality/religiosity), as well as outcome measures (life satisfaction and quality of life). RESULTS: Self-rated SA was significantly correlated to measures of specific dimensions (standardized ß from 0.11 to 0.39), most strongly with psychological functioning (ß = 0.391). The five dimension-specific measures together accounted for 16.7% of the variance in self-rated SA. Self-rated SA best predicted life satisfaction (R(2) = 0.26) more than any dimension-specific measure (R(2) from 0.05 to 0.17). Self-rated SA, vis-à-vis dimension-specific measures, was related to a different set of correlates, and was notably independent of chronological age, sex, education, socioeconomic status, and medical comorbidity, but was significantly related to ethnicity. CONCLUSION: The self-rated analogue scale is a sensitive global measure of SA encompassing a spectrum of underlying dimensions and subjective perspectives and its validity is well supported in this study.
Assuntos
Adaptação Psicológica , Envelhecimento/psicologia , Avaliação Geriátrica/métodos , Nível de Saúde , Saúde Mental , Comportamento Social , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Satisfação Pessoal , Qualidade de Vida/psicologia , Reprodutibilidade dos Testes , Autorrelato , EspiritualidadeRESUMO
The existing drugs for benign prostatic hyperplasia (BPH) are partially effective with undesirable side-effects; hence new agents acting by different mechanism(s) are required as supplements. Modulation of estrogen receptor signaling using selective estrogen receptor modulators (SERMs) offers an alternative approach for BPH management. Using human BPH-derived stromal cells and tissue explants in culture we evaluated two SERMs, DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2 H-1-benzopyran (BP) and Ormeloxifene (Orm) in comparison to Tamoxifen (Tam) and 4-hydroxytamoxifen (OHT). BP, OHT and Tam were more effective than Orm in reducing stromal cell proliferation of human BPH. BP was either equipotent or more effective than OHT and Tam in increasing estrogen receptor(ER)-ß, TGFß1, Fas and FasL, and in decreasing ER-α, AR, EGF-R and IGF-I expressions in BPH stromal cells. BP, Tam and Orm (1.0 mg/Kg) reduced rat prostate weights by almost same extent as Finasteride (Fin, 5.0 mg/Kg); however combination treatment (SERM+Fin) was more effective. BP was exceptionally efficient in reducing IGF-1 and cleaving PARP while combination treatments more effectively increased bax:bcl-2 ratio. Fin reduced acinar diameter and prostatic DHT level but increased testosterone, estradiol (E(2)) and E(2)/T+DHT ratio. SERMs, especially BP, reduced epithelial cell height drastically without significantly altering steroid hormone levels and E(2)/T+DHT ratio. Combination treatment reduced both acinar diameter and epithelial cell height with modest increase in E(2), T and E(2)/T+DHT. The study reveals the potential of SERMs per se for BPH management, and more effectively in combination with a 5α-reductase inhibitor. BP appears promising for further evaluation as a drug candidate for BPH and prostate cancer.