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M64HCl, which has drug-like properties, is a water-soluble Focal Adhesion Kinase (FAK) activator that promotes murine mucosal healing after ischemic or NSAID-induced injury. Since M64HCl has a short plasma half-life in vivo (less than two hours), it has been administered as a continuous infusion with osmotic minipumps in previous animal studies. However, the effects of more transient exposure to M64HCl on monolayer wound closure remained unclear. Herein, we compared the effects of shorter M64HCl treatment in vitro to continuous treatment for 24 hours on monolayer wound closure. We then investigated how long FAK activation and downstream ERK1/2 activation persist after two hours of M64HCl treatment in Caco-2 cells. M64HCl concentrations immediately after washing measured by mass spectrometry confirmed that M64HCl had been completely removed from the medium while intracellular concentrations had been reduced by 95%. Three-hour and four-hour M64HCl (100 nM) treatment promoted epithelial sheet migration over 24 hours similar to continuous 24-hour exposure. 100nM M64HCl did not increase cell number. Exposing cells twice with 2-hr exposures of M64HCl during a 24-hour period had a similar effect. Both FAK inhibitor PF-573228 (10 µM) and ERK kinase (MEK) inhibitor PD98059 (20 µM) reduced basal wound closure in the absence of M64HCl, and each completely prevented any stimulation of wound closure by M64HCl. Rho kinase inhibitor Y-27632 (20 µM) stimulated Caco-2 monolayer wound closure but no further increase was seen with M64HCl in the presence of Y-27632. M64HCl (100 nM) treatment for 3 hours stimulated Rho kinase activity. M64HCl decreased F-actin in Caco-2 cells. Furthermore, a two-hour treatment with M64HCl (100 nM) stimulated sustained FAK activation and ERK1/2 activation for up to 16 and hours 24 hours, respectively. These results suggest that transient M64HCl treatment promotes prolonged intestinal epithelial monolayer wound closure by stimulating sustained activation of the FAK/ERK1/2 pathway. Such molecules may be useful to promote gastrointestinal mucosal repair even with a relatively short half-life.
Assuntos
Mucosa Intestinal , Cicatrização , Humanos , Cicatrização/efeitos dos fármacos , Células CACO-2 , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Quinase 1 de Adesão Focal/metabolismo , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Movimento Celular/efeitos dos fármacos , Piridinas/farmacologia , Animais , Amidas/farmacologiaRESUMO
Increasing dietary fiber consumption is linked to lower colon cancer incidence, and this anticancer effect is tied to elevated levels of short-chain fatty acids (e.g., butyrate) because of the fermentation of fiber by colonic bacteria. While butyrate inhibits cancer cell proliferation, the impact on cancer cell type remains largely unknown. To test the hypothesis that butyrate displays different inhibitory potentials due to cancer cell type, we determined half-maximal inhibitory concentrations (IC50) of butyrate in HCT116, HT-29, and Caco-2 human colon cancer cell proliferation at 24, 48, and 72 h. The IC50 (mM) butyrate concentrations of HCT116, HT-29, and Caco-2 cells were [24 h, 1.14; 48 h, 0.83; 72 h, 0.86], [24 h, N/D; 48 h, 2.42; 72 h, 2.15], and [24 h, N/D; 48 h, N/D; 72 h, 2.15], respectively. At the molecular level, phosphorylated ERK1/2 and c-Myc survival signals were decreased by (>30%) in HCT116, HT-29, and Caco-2 cells treated with 4 mM butyrate. Conversely, butyrate displayed a stronger potential (>1-fold) for inducing apoptosis and nuclear p21 tumor suppressor in HCT116 cells compared to HT-29 and Caco-2 cells. Moreover, survival analysis demonstrated that a cohort with high p21 gene expression in their colon tissue significantly increased survival time compared to a low-p21-expression cohort of colon cancer patients. Collectively, the inhibitory efficacy of butyrate is cell type-specific and apoptosis-dependent.
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Butiratos , Neoplasias do Colo , Humanos , Butiratos/farmacologia , Células CACO-2 , Neoplasias do Colo/metabolismo , Apoptose , Ácidos Graxos Voláteis , Proliferação de CélulasRESUMO
Non-steroidal anti-inflammatory drugs (NSAIDs) injure the proximal and distal gut by different mechanisms. While many drugs reduce gastrointestinal injury, no drug directly stimulates mucosal wound healing. Focal adhesion kinase (FAK), a non-receptor tyrosine kinase, induces epithelial sheet migration. We synthesized and evaluated a water-soluble FAK-activating small molecule, M64HCl, with drug-like properties. Monolayer wound closure and Western blots measured migration and FAK phosphorylation in Caco-2 âcells, in vitro kinase assays established FAK activation, and pharmacologic tests assessed drug-like properties. 30 âmg/kg/day M64HCl was administered in two murine small intestine injury models for 4 days. M64HCl (0.1-1000 ânM) dose-dependently increased Caco-2 FAK-Tyr 397 phosphorylation, without activating Pyk2 and accelerated Caco-2 monolayer wound closure. M64HCl dose-responsively activates the FAK kinase domain vs. the non-salt M64, increasing the Vmax of ATP-binding. Pharmacologic tests suggested M64HCl has drug-like properties and is enterally absorbed. M64HCl 25 âmg/kg/day continuous infusion promoted healing of ischemic jejunal ulcers and indomethacin-induced small intestinal injury in C57Bl/6 mice. M64HCl-treated mice exhibited smaller ulcers 4 days after ischemic ulcer induction or indomethacin injury. Renal histology and plasma creatinine were normal. Mild hepatic inflammatory changes and ALT elevation were similar among M64HCl-treated mice and controls. M64HCl was concentrated in kidney and gastrointestinal mucosa and functional nephrectomy studies suggested predominantly urinary excretion. Little toxicity was observed in vitro or in single-dose mouse toxicity studies until >1000x higher than effective concentrations. M64HCl, a water-soluble FAK activator, promotes epithelial restitution and intestinal mucosal healing and may be useful to treat gut mucosal injury.
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ZINC40099027 (ZN27) is a specific focal adhesion kinase (FAK) activator that promotes murine mucosal wound closure after ischemic or NSAID-induced injury. Diverse motogenic pathways involve FAK, but the direct consequences of pure FAK activation have not been studied, and how ZN27-induced FAK activation stimulates wound closure remained unclear. We investigated signaling and focal adhesion (FA) turnover after FAK activation by ZN27 in Caco-2 cells, confirming key results in CCD841 cells. ZN27 increased Caco-2 FAK-Y-397, FAK-Y-576/7, paxillin-Y-118, and ERK 1/2 phosphorylation and decreased FAK-Y-925 phosphorylation, without altering FAK-Y-861, p38, Jnk, or Akt phosphorylation. ZN27 increased FAK-paxillin interaction while decreasing FAK-Grb2 association. ZN27 increased membrane-associated FAK-Y-397 and FAK-Y-576/7 phosphorylation and paxillin-Y-118 and ERK 1/2 phosphorylation but decreased FAK-Y-925 phosphorylation without altering Src or Grb2. Moreover, ZN27 increased the fluorescence intensity of GFP-FAK and pFAK-Y397 in FAs and increased the total number of FAs but reduced their size in GFP-FAK-transfected Caco-2 cells, consistent with increased FA turnover. In contrast, FAK-Y397F transfection prevented ZN27 effects on FAK size and number and FAK and pFAK fluorescent intensity in FAs. We confirmed the proposed FAK/paxillin/ERK pathway using PP2 and U0126 to block Src and MEK1/2 in Caco-2 and CCD841 cells. These results suggest that ZN27 promotes intestinal epithelial monolayer defect closure by stimulating autophosphorylation of FAK in the cytosol, distinct from classical models of FAK activation in the FA. Phosphorylated FAK translocates to the membrane, where its downstream substrates paxillin and ERK are phosphorylated, leading to FA turnover and human intestinal epithelial cell migration.
Assuntos
Sistema de Sinalização das MAP Quinases , Humanos , Camundongos , Animais , Paxilina/metabolismo , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Células CACO-2 , Citosol/metabolismo , Quinase 1 de Adesão Focal , Fosforilação , Movimento CelularRESUMO
The integrity of the gastrointestinal mucosa plays a crucial role in gut homeostasis, which depends upon the balance between mucosal injury by destructive factors and healing via protective factors. The persistence of noxious agents such as acid, pepsin, nonsteroidal anti-inflammatory drugs, or Helicobacter pylori breaks down the mucosal barrier and injury occurs. Depending upon the size and site of the wound, it is healed by complex and overlapping processes involving membrane resealing, cell spreading, purse-string contraction, restitution, differentiation, angiogenesis, and vasculogenesis, each modulated by extracellular regulators. Unfortunately, the gut does not always heal, leading to such pathology as peptic ulcers or inflammatory bowel disease. Currently available therapeutics such as proton pump inhibitors, histamine-2 receptor antagonists, sucralfate, 5-aminosalicylate, antibiotics, corticosteroids, and immunosuppressants all attempt to minimize or reduce injury to the gastrointestinal tract. More recent studies have focused on improving mucosal defense or directly promoting mucosal repair. Many investigations have sought to enhance mucosal defense by stimulating mucus secretion, mucosal blood flow, or tight junction function. Conversely, new attempts to directly promote mucosal repair target proteins that modulate cytoskeleton dynamics such as tubulin, talin, Ehm2, filamin-a, gelsolin, and flightless I or that proteins regulate focal adhesions dynamics such as focal adhesion kinase. This article summarizes the pathobiology of gastrointestinal mucosal healing and reviews potential new therapeutic targets.
Assuntos
Úlcera Péptica , Anti-Inflamatórios não Esteroides/farmacologia , Mucosa Gástrica/metabolismo , Homeostase , Humanos , Úlcera Péptica/tratamento farmacológico , Sucralfato/uso terapêuticoRESUMO
OBJECTIVE: The aim of this study was to compare exercise, continuous short-wave diathermy (SWD) and intermittent SWD treatment modalities and to evaluate the effects of these treatments on chronic back pain and depression. METHODS: This study is an intervention trial which evaluated patients who applied to our clinic due to chronic low back pain between 2008-2009. The study group consisted of 90 patients between the ages of 40-65 who had had low back pain for more than 6 months. The patients were randomized into three groups. The first group received placebo short-wave diathermy, the second group received continuous short-wave diathermy, and the third group received pulsed short-wave diathermy. Pain was evaluated by Visual Analog Scale (VAS) and the Pain Disability Index (PDI).The Modified Oswestry Low Back Pain Disability Questionnaire Form was used for the measurement of functional deficiency and the Beck Depression Inventory (BDI) was used for the evaluation of depression.All scales were performed before the treatment, immediately after treatment and 3 months after treatment. RESULTS: Significant decreases in PDI and VAS scores were found in all groups (p<0.05 for each). Similarly, there was a significant improvement in all groups in terms of functional deficiency(p<0.001 for each), while no differences were found between groups (p = 0.895). In terms of BDI scores, there was no improvement in those receiving only exercise, while Group 2 and 3 had significant improvements (p <0.05). When groups were compared for BDI scores, no differences were found between any of the groups (p = 0.189). CONCLUSION: Continuous SWD treatment with exercise was found to be more effective in reducing pain in patients with chronic low back pain than other treatment modalities used in our study. Although there was no significant difference between the groups in terms of depressive mood, it was found that those receiving continuous and pulsed SWD treatment had significant improvements in depression as measured by the BDI.
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Diatermia , Dor Lombar , Pré-Escolar , Depressão/terapia , Humanos , Dor Lombar/terapia , Manejo da Dor , Medição da Dor , Resultado do TratamentoRESUMO
Nonsteroidal anti-inflammatory drugs cause gastric ulcers and gastritis. No drug that treats GI injury directly stimulates mucosal healing. ZINC40099027 (ZN27) activates focal adhesion kinase (FAK) and heals acute indomethacin-induced small bowel injury. We investigated the efficacy of ZN27 in rat and human gastric epithelial cells and ongoing aspirin-associated gastric injury. ZN27 (10 nM) stimulated FAK activation and wound closure in rat and human gastric cell lines. C57BL/6J mice were treated with 300 mg/kg/day aspirin for five days to induce ongoing gastric injury. One day after the initial injury, mice received 900 µg/kg/6 h ZN27, 10 mg/kg/day omeprazole, or 900 µg/kg/6 h ZN27 plus 10 mg/kg/day omeprazole. Like omeprazole, ZN27 reduced gastric injury vs. vehicle controls. ZN27-treated mice displayed better gastric architecture, with thicker mucosa and less hyperemia, inflammation, and submucosal edema, and lost less weight than vehicle controls. Gastric pH, serum creatinine, serum alanine aminotransferase (ALT), and renal and hepatic histology were unaffected by ZN27. Blinded scoring of pFAK-Y-397 immunoreactivity at the edge of ZN27-treated lesions demonstrated increased FAK activation, compared to vehicle-treated lesions, confirming target activation in vivo. These results suggest that ZN27 ameliorates ongoing aspirin-associated gastric mucosal injury by a pathway involving FAK activation. ZN27-derivatives may be useful to promote gastric mucosal repair.
Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Aspirina/efeitos adversos , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Mucosa Gástrica/lesões , Mucosa Gástrica/patologia , Cicatrização/efeitos dos fármacos , Alanina Transaminase/sangue , Animais , Linhagem Celular , Creatinina/sangue , Modelos Animais de Doenças , Ativação Enzimática/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Feminino , Mucosa Gástrica/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Hiperemia/patologia , Inflamação/patologia , Antígeno Ki-67/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos , Ratos , Redução de Peso/efeitos dos fármacosRESUMO
Gastrointestinal mucosal wounds are common to patients injured by factors as diverse as drugs, inflammatory bowel disease, peptic ulcers, and necrotizing enterocolitis. However, although many drugs are used to ameliorate injurious factors, there is no drug available to actually stimulate mucosal wound healing. Focal adhesion kinase (FAK), a nonreceptor tyrosine kinase, induces epithelial sheet migration and wound healing, making FAK a potential pharmacological target in this regard. In our previous research, we found a lead compound with drug-like properties, ZINC40099027, which promotes FAK phosphorylation, inducing mucosal healing in murine models. Herein we describe the design and optimization of a small library of novel FAK activators based on ZINC40099027 and their applications toward human intestinal epithelial wound closure and mouse ulcer healing.
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As a result of the current demographics, increased projections of osteoporosis (OP) and prevalence of the disease in Turkey, a panel of multidisciplinary experts developed a thorough review to assist clinicians in identifying OP and associated fracture risk patients, diagnosing the disease with the appropriate available diagnostic methods, classifying the disease, and initiating appropriate treatment. The panel expects to increase the awareness of this prevalent disease, decrease consequences of OP with corresponding cost savings and, ultimately, decrease the overall burden of OP and related fractures in Turkey. BACKGROUND: OP is not officially accepted as a chronic disease in Turkey despite the high prevalence and predicted increase in the following years. However, there are areas where the country is performing well, such as having a country-specific fracture risk assessment model, DXA access, and the uptake of FRAX. Additional efforts are required to decrease the existing treatment gap estimating 75-90% of patients do not receive pharmacological intervention for secondary prevention, and the diagnosis rate is around 25%. METHODS: A selected panel of Turkish experts in fields related to osteoporosis was provided with a series of relevant questions to address prior to the multi-day conference. Within this conference, each narrative was discussed and edited by the entire group, through numerous drafts and rounds of discussion until a consensus was achieved. Represented in the panel were a number of societies including The Turkish Osteoporosis Society, The Society of Endocrinology and Metabolism of Turkey (SEMT), and The Turkish Society of Physical Medicine and Rehabilitation. RESULTS: Standardized general guidelines to identify OP and related fractures and at-risk population in Turkey, which will enable clinicians to accurately and effectively diagnose the disease, treat the appropriate patients with available pharmacological and non-pharmacological treatments and decrease the burden of the disease. CONCLUSIONS: This manuscript provides a review of the current state of OP and related fractures in Turkey. Moreover, this manuscript reviews current international guidelines and national studies and proposes a number of helpful country-specific classifications that can be used by healthcare providers caring for the at-risk population. Additionally, the panel proposes practical recommendations that should be implemented nationally in order to decrease the burden of OP and related fractures and effectively preventing the burden in future generations.
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Conservadores da Densidade Óssea/uso terapêutico , Densidade Óssea/efeitos dos fármacos , Cálcio/uso terapêutico , Osteoporose/diagnóstico por imagem , Osteoporose/tratamento farmacológico , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/tratamento farmacológico , Vitamina D/uso terapêutico , Consenso , Suplementos Nutricionais , Fraturas Ósseas/etiologia , Humanos , Masculino , Osteoporose/epidemiologia , Fraturas por Osteoporose/epidemiologia , Guias de Prática Clínica como Assunto , Prevalência , Medição de Risco , Sociedades Médicas , Resultado do Tratamento , Turquia/epidemiologiaRESUMO
Although positive effect of kinesiotaping in reducing back pain in addition to exercise was observed in 6-week follow-up, no additional contribution to exercise was demonstrated in kyphosis angle and balance assessment. Instantaneous positive effect of taping was observed in kyphosis angle and static balance measurement using a SportKAT device measurements 30 min after taping. OBJECTIVE: The present study aims to investigate whether kinesiotaping for posture correction in patients with osteoporosis-related increased kyphosis provides additional benefits to routine osteoporosis and balance exercises in reducing dorsal kyphosis angle, pain, and balance. METHOD: A single-center, parallel-group randomized controlled trial with unblinded assessments at baseline, week 3, and week 6 and additional measures 30 min immediately after taping in intervention group only. Forty-two female osteoporotic patients with hyperkyphosis were enrolled and randomized into 2 groups. The intervention group received an exercise program plus 3 sessions of kinesiotaping over the upper back; the control group received only an exercise program. The primary outcome measure was dorsal kyphosis angle, measured using a digital inclinometer. Secondary outcome measures were pain assessed on a visual analog scale (VAS 0-10 cm) and balance assessed with the Berg Balance Scale and SportKAT device. RESULTS: The study was conducted on 22 patients with an average age of 64 ± 7.08 in the control group and 20 patients with an average age of 63.1 ± 8.8 in the treatment group. There was not a significant difference when dorsal kyphosis angle of the two groups was compared in terms of the change between the baseline and week 6. The mean change in the control group was 0.86 ± 2 while it was 0.70 ± 1.75 in the intervention group. No significant difference was detected between the groups in terms of balance measurements. Significant differences were seen in favor of the intervention group when the VAS pain scores of the two groups were compared in terms of the change between the baseline and week 3 (p < 0.001) and the baseline and week 6 (p < 0.001), while no such difference was identified when the changes between weeks 3 and 6 were compared between the two groups. A significant effect on dorsal kyphosis angle and balance was also shown in the treatment group 30 min after taping. CONCLUSION: Application of kinesiotaping may have short-term positive effects on pain, but is unlikely to have significant effects on kyphosis angle or balance for women with osteoporosis. Positive changes seen in kyphosis angle and balance 30 min after taping are short-lived.
Assuntos
Fita Atlética , Cifose/terapia , Osteoporose Pós-Menopausa/complicações , Equilíbrio Postural/fisiologia , Postura/fisiologia , Idoso , Dor nas Costas/etiologia , Dor nas Costas/terapia , Terapia por Exercício/métodos , Feminino , Humanos , Cifose/etiologia , Cifose/fisiopatologia , Pessoa de Meia-Idade , Osteoporose Pós-Menopausa/fisiopatologia , Vértebras Torácicas , Resultado do TratamentoRESUMO
OBJECTIVES: This study aims to estimate the prevalence of rheumatoid arthritis (RA) and spondyloarthritis (SpA) in Turkey using the same telephone questionnaire developed for screening RA and SpA in France and used in Serbia and Lithuania. MATERIAL AND METHODS: The study was performed in two steps. In step I, the French questionnaire was translated into Turkish and validated through a group of 200 patients (80 males, 120 females; mean age 44.0±13.1 years; range 19 to 75 years) followed up at the rheumatology departments of University Hospitals in Antalya and Ankara. In step II, the validated Turkish questionnaire was administered face-to-face to randomly selected 4,012 subjects (1,670 males, 2,342 females; mean age 41.5±16.8 years; range 16 to 97 years) by trained general practitioners across the country, in 25 prov- inces for case detection. The subjects who were suspected of having RA or SpA in accordance with the questionnaire were invited to the nearest university hospital for rheumatologic examination in order to confirm the diagnosis. RESULTS: In step II, a total of 25 subjects (2 males, 23 females) were diagnosed as RA. The standardized RA prevalence for the general population of Turkey was calculated as 0.56% (95% confidence interval [CI]; 0.33-0.79), 0.10% (95% CI; -0.05-0.25) for males and 0.89% (95% CI; 0.51-1.27) for females. A total of 18 subjects (3 males, 15 females) were diagnosed as SpA. The standardized SpA prevalence for the general population of Turkey was 0.46% (95% CI; 0.25-0.67), 0.17% (95% CI; -0.03-0.37) for males and 0.65% (95% CI; 0.32-0.98) for females. The prevalence of RA was highest in the Northern region (2.00%) and the prevalence of SpA was highest in the Central region (1.49%). CONCLUSION: The prevalences of RA and SpA in Turkey are close to each other and there are significant inter-regional variations in prevalences of both RA and SpA.
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OBJECTIVE: To compare the effectiveness of transcutaneous electrical nerve stimulation (TENS), interferential currents (IFCs), and shortwave diathermy (SWD) against each other and sham intervention with exercise training and education as a multimodal package. DESIGN: A double-blind, randomized, controlled, multicenter trial. SETTING: Departments of physical medicine and rehabilitation in 4 centers. PARTICIPANTS: Patients (N=203) with knee osteoarthritis (OA). INTERVENTIONS: The patients were randomized by the principal center into the following 6 treatment groups: TENS sham, TENS, IFCs sham, IFCs, SWD sham, and SWD. All interventions were applied 5 times a week for 3 weeks. In addition, exercises and an education program were given. The exercises were carried out as part of a home-based training program after 3 weeks' supervised group exercise. MAIN OUTCOME MEASURES: Primary outcome was a visual analog scale (0-100mm) to assess knee pain. Other outcome measures were time to walk a distance of 15m, range of motion, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Nottingham Health Profile, and paracetamol intake (in grams). RESULTS: We found a significant decrease in all assessment parameters (P<.05), without a significant difference among the groups except WOMAC stiffness score and range of motion. However, the intake of paracetamol was significantly lower in each treatment group when compared with the sham groups at 3 months (P<.05). Also, the patients in the IFCs group used a lower amount of paracetamol at 6 months (P<.05) in comparison with the IFCs sham group. CONCLUSIONS: Although all groups showed significant improvements, we can suggest that the use of physical therapy agents in knee OA provided additional benefits in improving pain because paracetamol intake was significantly higher in the patients who were treated with 3 sham interventions in addition to exercise and education.
Assuntos
Diatermia , Osteoartrite do Joelho/terapia , Estimulação Elétrica Nervosa Transcutânea , Acetaminofen/uso terapêutico , Idoso , Análise de Variância , Artralgia/etiologia , Terapia Combinada , Método Duplo-Cego , Terapia por Exercício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/fisiopatologia , Medição da Dor , Educação de Pacientes como Assunto , Amplitude de Movimento Articular , Fatores de Tempo , Caminhada/fisiologiaRESUMO
BACKGROUND/OBJECTIVE: To show the efficacy, safety, and tolerability of sildenafil in men with erectile dysfunction (ED) associated with complete or incomplete spinal cord injury (SCI) and to assess its effects on quality of life (QoL) using the Life-Satisfaction Check List. METHODS: This was a placebo-controlled, multicenter, randomized, double-blind, flexible-dose, 2-way crossover study with a 2-week washout period between each phase. Patients with ED attributable to SCI (Sexual Health Inventory-Male score < or =21) received 50 to 100 mg sildenafil (n = 24) or placebo (n = 26). RESULTS: Compared with placebo, sildenafil produced higher levels of successful sexual stimulation, intercourse success, satisfaction with sexual life and sexual relationship, erectile function, overall sexual satisfaction, and an improved Erectile Dysfunction Inventory of Treatment Satisfaction score, with no clinically relevant effects on vital signs. Sildenafil seemed more effective in patients with incomplete SCI than in those with complete SCI, producing significant improvements, compared with placebo, in a number of measures only in patients with incomplete SCI. All patients who expressed a preference selected sildenafil over placebo, although the drug had no effect on patient QoL. Sildenafil was well tolerated, with a profile comparable to that of placebo. CONCLUSIONS: Compared with placebo, treatment with oral sildenafil safely and effectively improved erectile function in patients with ED attributable to SCI, especially in those with incomplete injury, and was the agent of choice in those who expressed a preference.
Assuntos
Disfunção Erétil/tratamento farmacológico , Estudos de Avaliação como Assunto , Inibidores de Fosfodiesterase/uso terapêutico , Piperazinas/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Sulfonas/uso terapêutico , Adulto , Análise de Variância , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Disfunção Erétil/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Purinas/uso terapêutico , Índice de Gravidade de Doença , Citrato de Sildenafila , Traumatismos da Medula Espinal/complicações , Fatores de TempoRESUMO
The aim of this cross-sectional study was to define the normative data for stiffness index in a large sample of Turkish population and to clarify sex differences as well as age-related changes. A total of 10,435 subjects (aged 18-89 yr) were screened with calcaneal ultrasound and were requested to complete a detailed questionnaire listing all important risk factors, diseases, and treatments affecting bone metabolism. To be included in the study, subjects had to be free of any disease and any medical treatment known to affect bone metabolism. A total of 8,156 subjects (1,389 males and 6,767 females) were included in the study. Normative data was expressed using two statistical models including mean and 95th percentile, and regression analysis. The mean value of stiffness index in females peaked in the third decade, whereas in males it peaked in the age group of 18-29 yr. The stiffness index of females decreased by 24.26%. The total age-related decrease was 17.8% for stiffness index in the males. Stiffness index in males was a function of age (negatively) and body mass index (positively). Stiffness index in females was a function of age (negatively) and weight (positively). The results of this study could be useful as a guide for comparing the data of individual studies and may serve as reference normative data for the Turkish population.
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Calcâneo/diagnóstico por imagem , Adolescente , Adulto , Fatores Etários , Índice de Massa Corporal , Calcâneo/fisiopatologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/diagnóstico , Valores de Referência , Fatores Sexuais , Turquia , UltrassonografiaRESUMO
The purpose of this study was to investigate the associations of tooth loss with skeletal bone mass, years since menopause, educational level, current smoking status, dietary calcium intake, and number of pregnancies in postmenopausal osteoporotic women in Turkey. The study population consisted of 1171 postmenopausal women aged 40-86 years (mean age, 61.19 +/- 7.28 years). A detailed history was obtained from all women, including relevant lifestyle parameters, risk factors, and measurements of weight and height. Women were separated into three groups according to the number of teeth remaining as group 1 (edentulous, 457 women), group 2 (10 or fewer teeth, 232 women), and group 3 (more than 10 teeth remaining, 482 women). There was no significant difference among the three groups in mean age and menopausal age ( P < 0.05). Body mass index of group 1 was significantly higher than that of group 2 ( P< 0.01). Educational level was significantly different between three groups: groups 1 and 2 ( P< 0.001), groups 1 and 3 ( P< 0.0001), and groups 2 and 3 ( P< 0.001). Educational level was lowest in group 1 and highest in group 3. Despite a low ratio of cigarette smoking in general, a smoking habit was most prevalent in group 3 and least in group 2. The ratio of women receiving adequate calcium was significantly lower in group 1 than in other groups ( P< 0.001); mean calcium intake was similar in all groups. The number of pregnancies was significantly higher in group 1 than in other groups ( P< 0.001). Lumbar bone mineral density (BMD) of group 1 was significantly lower than that of groups 2 and 3 ( P< 0.001). Although no significant difference was found between groups 1 and 3, femoral neck BMD of group 2 was less than in others, and differences between groups 1 and 2 and between groups 2 and 3 ( P< 0.001) were significant. Lumbar bone mineral content (BMC) of group 1 was significantly lower than that of groups 2 and 3 ( P< 0.001), and lumbar BMC in group 2 was significantly higher than in group 3 ( P< 0.05). Femoral neck BMC in group 1 was significantly higher than in groups 2 and 3 ( P< 0.001). In conclusion, lumbar BMD and BMC in the edentulous group were significantly lower, whereas femoral neck BMD and BMC were significantly higher in edentulous group compared with the others. Our findings indicated that improvement in lifestyle factors and nutritional strategies for the treatment and prevention of osteoporosis may have additional benefit in reducing tooth loss.
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Osteoporose/complicações , Pós-Menopausa , Perda de Dente/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Densidade Óssea , Cálcio da Dieta/administração & dosagem , Humanos , Pessoa de Meia-IdadeRESUMO
Risk factors which have been associated with low bone mass are multifactorial and represent regional differences between and within countries. The purpose of this study was to evaluate the possible risk factors of low tibial speed of sound (tSOS), which determines cortical bone status among residents of urban regions in Ankara, Izmir, and Istanbul, in Turkey, and also to compare groups of different socioeconomic status (SES). A total of 1,026 subjects (63% women and 53% of low socioeconomic status) 40-70 years old were included in the study. Risk factors of osteoporosis were determined using the European Vertebral Osteoporosis Study (EVOS) questionnaire, and the bone status was screened by tSOS. Socioeconomic status was found to be among the major risk factors of low tSOS in our population (odds ratio 0.39, 95% confidence interval 0.26-0.58), besides the well-known risk factors such as age and gender. Therefore, we suggest that SES is an important determinant of cortical bone status. Additionally, our results confirmed the correlation between tSOS and the clinical determinants of bone mass.
Assuntos
Densidade Óssea/fisiologia , Osteoporose/etiologia , Osteoporose/fisiopatologia , Som , Tíbia/fisiopatologia , Adulto , Fatores Etários , Idoso , Estudos de Casos e Controles , Estudos Transversais , Escolaridade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoporose/economia , Fatores de Risco , Fatores Sexuais , Classe Social , Fatores Socioeconômicos , Inquéritos e Questionários , TurquiaRESUMO
OBJECTIVE: To assess the effect of nerve and tendon gliding exercises in carpal tunnel syndrome. DESIGN: The study was a prospective, randomized, before-and-after treatment trial. A total of 28 patients with the diagnosis of carpal tunnel syndrome in 36 hands were randomly assigned to two groups. A custom made neutral volar wrist splint was given to group 1 and group 2. The patients were instructed to wear the splints all night and during the day as much as possible for 4 wk. The patients in group 2 were also instructed to perform series of nerve and tendon gliding exercises in addition to the splint treatment. Patients were evaluated with clinical parameters, a functional status scale, and a symptom severity scale. RESULTS: At the end of treatment, statistically significant improvement was obtained in all parameters in both groups. The improvement in group 2 was slightly greater, but the difference between the groups was not significant, except for the lateral pinch strength value. Patient satisfaction was investigated during the follow-up period, ranging from 5 to 11 mo, with a mean of 8 mo. A total of 72% of the patients in group 1 and 93% of the patients in group 2 reported good or excellent results. The difference between the two groups was not statistically significant. CONCLUSION: Although the results in group 2 were better than group 1, the difference was not statistically significant. Further investigations are required to establish the role of nerve and tendon gliding exercises in the treatment of carpal tunnel syndrome.