Proline modulates the effect of bisphosphonate on calcium levels and adenosine triphosphate production in cell lines derived from bovine Echinococcus granulosus protoscoleces.

Bisphosphonates have been proposed as pharmacological agents against parasite and cancer cell growth. The effect of these compounds on helminthic cell viability and acellular compartment morphology, however, has not yet been studied. The effects of different types of bisphosphonates, namely etidronate (EHDP), pamidronate (APD), alendronate (ABP), ibandronate (IB) and olpadronate (OPD), and their interaction with amiloride, 1,25-dihydroxycholecalciferol (D3) and proline were evaluated on a cell line derived from bovine Echinococcus granulousus protoscoleces (EGPE) that forms cystic colonies in agarose. The EGPE cell line allowed testing the effect of bisphosphonates alone and in association with other compounds that could modulate calcium apposition/deposition, and were useful in measuring the impact of these compounds on cell growth, cystic colony formation and calcium storage. Decreased cell growth and cystic colony formation were found with EHDP, IB and OPD, and increased calcium storage with EHDP only. Calcium storage in EGPE cells appeared to be sensitive to the effect of amiloride, D3 and proline. Proline decreased calcium storage and increased colony formation. Changes in calcium storage may be associated with degenerative changes of the cysts, as shown in the in vitro colony model and linked to an adenosine triphosphate (ATP) decrease. In conclusion, bisphosphonates could be suitable tempering drugs to treat cestode infections.

Biomechanical background for a noninvasive assessment of bone strength and muscle-bone interactions.

New concepts and methods of study in bone biomechanics defy the prevailing idea that bone strength is determined by a systemically-controlled "mineralized mass" which grows until reaching a peak and then is lost at individually-specific rates. In case of bones, "mass" represents actually the substratum of a structure, the stiffness of which does not depend on the mass, but on the intrinsic stiffness and the spatial distribution of the mineralized material. A feed-back system called "bone mechanostat" seems to orient the osteoblastic and osteoclastic processes of bone, modeling and remodeling, according to the sensing by osteocytes of strains caused in the structure by mechanical usage of the skeleton, in specific directions as determined principally by the customary contractions of regional muscles and impact forces. The endocrine-metabolic systems, crucial for the normal skeletal development, modulate the work of osteocytes, blasts and clasts in a systemic way (i.e., not related to a specific direction of the stimuli). Therefore, they tend actually to interact with, rather than contribute to, the biomechanical control of bone structure. Furthermore, no feed-back loop enabling a cybernetic relationship of those systems with bone is known. Instead of passively letting hormones regulate their "mass" in order to optimize their strength, bones would actively self-regulate their architecture following an anisotropic pattern in order to optimize their stiffness (the only known variable to be ever controlled in the skeleton) and strength "despite of" the endocrine systems. Three practical questions derive from those ideas: 1. Osteoporoses are not "intense osteopenias" but "osteopenic fragilities". 2. The diagnosis of osteopenia could be solved densitometrically; but that of bone fragility is a biomechanical problem which requires auxiliary resources for evaluating the stiffness and the spatial distribution of the mineralized material. 3. Osteopenias and osteoporoses should be on time evaluated as related to the mass or strength of the regional muscles, respectively, in order to differentiate between the "primary" (intrinsic lesion of the mechanostat) or "secondary" (systemic) etiologies and the biomechanical origin (disuse) in each case, with important therapeutic implications.

Cinetica de la quimioluminescencia del intestino de la rata durante isquemia y reperfusion / Kinetics of luminiscence of rat intestine during ischemia and reperfusion

En este estudio se determina in vivo la quimioluminescencia del intestino de rata sometido a isquemia provocada por una ligadura oclusiva y luego durante la reperfusión al desligar el órgano. La quimioluminescencia del órgano en función del tiempo, en animales sometidos a 2, 5 y 10 minutos de isquemia tiende a disminuir rápidamente. En intestinos de ratas ligados durante 2 minutos y luego desligados, comparados con intestinos no ligados, se muestra un exceso medio de quimioluminescencia del 44% aproximadamente luego de 2 a 3 minutos de iniciada la reperfusión. Este exceso inicial de quimioluminescencia se mantiene entre los primeros 10 a 20 minutos posteriores a la desligadura, no habiéndose registrado períodos más prolongados. la administración de un atrapador de radicales libres, ácido tióctico 100 mg/kg, i.p. evita o reduce el exceso de quimioluminescencia descripto, por un período de por lo menos 20 minutos. Estos datos concuerdan con la sugerencia de que la generación excesiva de radicales del oxígeno tiene lugar in vivo desde los minutos iniciales de la reperfusión y puede ser la consecuencia de cambios enzimáticos producidos muy rápidamente durante el anterior período hipóxico

Cinetica de la quimioluminescencia del intestino de la rata durante isquemia y reperfusion / Kinetics of luminiscence of rat intestine during ischemia and reperfusion

En este estudio se determina in vivo la quimioluminescencia del intestino de rata sometido a isquemia provocada por una ligadura oclusiva y luego durante la reperfusión al desligar el órgano. La quimioluminescencia del órgano en función del tiempo, en animales sometidos a 2, 5 y 10 minutos de isquemia tiende a disminuir rápidamente. En intestinos de ratas ligados durante 2 minutos y luego desligados, comparados con intestinos no ligados, se muestra un exceso medio de quimioluminescencia del 44% aproximadamente luego de 2 a 3 minutos de iniciada la reperfusión. Este exceso inicial de quimioluminescencia se mantiene entre los primeros 10 a 20 minutos posteriores a la desligadura, no habiéndose registrado períodos más prolongados. la administración de un atrapador de radicales libres, ácido tióctico 100 mg/kg, i.p. evita o reduce el exceso de quimioluminescencia descripto, por un período de por lo menos 20 minutos. Estos datos concuerdan con la sugerencia de que la generación excesiva de radicales del oxígeno tiene lugar in vivo desde los minutos iniciales de la reperfusión y puede ser la consecuencia de cambios enzimáticos producidos muy rápidamente durante el anterior período hipóxico (AU)