RESUMEN
Previous studies of the mechanical properties of tendons in the upper limb have used embalmed specimens or sub-optimal methods of measurement. The aim of this study was to determine the biomechanical properties of all tendons from five fresh frozen cadaveric forearms using updated methodology. The cross-sectional area of tendons was accurately measured using a laser reflectance system. Tensile testing was done in a precision servo-hydraulic device with cryo-clamp fixation. We determined that the cross-sectional area of some tendons is variable and directly influences the calculated material properties; visual estimation of this is unreliable. Data trends illustrate that digital extensor tendons possess the greatest tensile strength and a higher Young's modulus than other tendon types.
Asunto(s)
Antebrazo/fisiología , Tendones/fisiología , Resistencia a la Tracción/fisiología , Anciano , Fenómenos Biomecánicos/fisiología , Cadáver , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVE: Bisphosphonates are commonly used anti-osteoporotic drugs which have controversial effects on joint diseases including osteoarthritis. Certain bisphosphonates have been shown to have anabolic effects on cartilage which could have important ramifications for their proposed effects in vivo; however, the underlying mechanisms are poorly understood. Thus, the purpose of this study was to characterize the effects of clodronate on primary articular chondrocyte metabolism and to determine the underlying signaling pathways responsible. DESIGN: The effects of clodronate and pamidronate on extracellular matrix (ECM) biosynthesis, accumulation and MMP-13 activity were observed in high density, 3D cultures of bovine articular chondrocytes for up to 4 weeks were evaluated. Mechanisms were delineated by measuring intracellular Ca(2+) signaling and the effects of pharmacologic inhibition of the purinergic receptor pathway. RESULTS: Clodronate (100 µM) induced an anabolic effect (increased biosynthesis by 13-14%) which resulted in an 89-90% increase in ECM accumulation after 4 weeks of culture and without an associated effect on matrix turn-over. Stimulation by clodronate resulted in a 3.3-fold increase in Ca(2+) signaling and pharmacological inhibitor experiments suggested that the anabolic effects exerted by clodronate are transduced through the purinergic receptor pathway. CONCLUSIONS: These findings support the previous notion that certain bisphosphonates may be useful as adjunctive therapies to potentially ameliorate progression of cartilage degeneration and improve arthritis management.
Asunto(s)
Anabolizantes/farmacología , Conservadores de la Densidad Ósea/farmacología , Cartílago Articular/efectos de los fármacos , Condrocitos/efectos de los fármacos , Ácido Clodrónico/farmacología , Receptores Purinérgicos/fisiología , Anabolizantes/administración & dosificación , Animales , Conservadores de la Densidad Ósea/administración & dosificación , Señalización del Calcio/efectos de los fármacos , Señalización del Calcio/fisiología , Cartílago Articular/citología , Cartílago Articular/metabolismo , Bovinos , Células Cultivadas , Condrocitos/metabolismo , Ácido Clodrónico/administración & dosificación , Difosfonatos/administración & dosificación , Difosfonatos/farmacología , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos/métodos , Matriz Extracelular/metabolismo , Metaloproteinasa 13 de la Matriz/metabolismo , Pamidronato , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
Stilbenes possess a variety of biological activities including chemopreventive activity. This study was conducted to evaluate the structural activity relationships of six methoxylated stilbene analogues with respect to their cytotoxic effects and antioxidant activities on HepG2 hepatoma and Chang liver cells. The cytotoxic and total antioxidant activities of six stilbene analogues were determined by MTT and Ferric Reducing Antioxidant Power (FRAP) assays, respectively. We found that the cis-methoxylated stilbene: (Z)-3,4,4'-trimethoxystilbene was the most potent and selective antiproliferative agent (IC50 89 µM) in HepG2 cells. For the total antioxidant activity, compounds possessing hydroxyl groups at the 4' position namely (E)-3-methoxy-4'-hydroxystilbene, (E)-3,5-dimethoxy-4'-hydroxystilbene (pterostilbene), (E)-4-methoxy-4'-hydroxystilbene showed the highest antioxidant activity. Structure activity relationship studies of these compounds demonstrated that the cytotoxic effect and antioxidant activities of the tested compounds in this study were structurally dependent.
Asunto(s)
Anticarcinógenos/farmacología , Antioxidantes/farmacología , Hígado/efectos de los fármacos , Estilbenos/farmacología , Anticarcinógenos/química , Antioxidantes/química , Técnicas de Cultivo de Célula , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Células Hep G2 , Humanos , Hígado/metabolismo , Hígado/patología , Estructura Molecular , Estilbenos/química , Relación Estructura-ActividadRESUMEN
[equation--see text] Introducing 3-methoxy or 3,5-dimethoxy substituents on the 4-hydroxyphenacyl (pHP) photoremovable protecting group has been explored with two excitatory gamma-amino acids, L-glutamic acid and gamma-amino butyric acid (GABA). These substituents significantly extend the absorption range of the pHP chromophore, e.g., the tail of absorption bands of 2a,b extend above 400 nm, well beyond the absorptions of aromatic amino acids and nucleotides. Irradiation releases the amino acids with rate constants of approximately 10(7) s(-)(1) and appearance efficiencies (Phi(app)) of 0.03-0.04. The photoproducts are formed through the pHP excited triplet and are primarily products of photoreduction and photohydrolysis. 1a,b also rearranged to the phenylacetic acid 3.
Asunto(s)
Fotólisis , Acetofenonas/química , Acetofenonas/efectos de la radiación , Animales , Bicuculina/farmacología , Conductividad Eléctrica , Electrones , Ácido Glutámico/química , Ácido Glutámico/farmacología , Ácido Glutámico/efectos de la radiación , Hipocampo/citología , Canales Iónicos/efectos de los fármacos , Luz , Mediciones Luminiscentes , Neuronas/efectos de los fármacos , Neuronas/fisiología , Neuronas/efectos de la radiación , Ratas , Ácido gamma-Aminobutírico/química , Ácido gamma-Aminobutírico/farmacología , Ácido gamma-Aminobutírico/efectos de la radiaciónRESUMEN
A large phytochemical survey of the flora of the Malaysian Peninsula and Sabah is described, covering the systematic search for alkaloids, and partly, for saponins and flavonoids. Details of some chemical studies are reported. This emphasizes the great interest of such a study.