Nélida Mondelo - Academia.edu (original) (raw)
Papers by Nélida Mondelo
Tumor Biology, 1999
Paraneoplastic syndromes are rarely described in animal models. It may be useful to have a suitab... more Paraneoplastic syndromes are rarely described in animal models. It may be useful to have a suitable experimental model to study the mechanisms by which they are produced. In this study, we describe a murine lung adenocarcinoma, P07, which presents hypercalcemia, leukocytosis and cachexia. We determined the presence of PTHrP in plasma as well as GM-CSF produced by P07 cells. TNF-alpha, which is responsible for cachexia, could neither be detected in serum nor in P07 cell supernatants. We conclude that this model, which shows paraneoplastic syndromes similar to those of lung tumor patients, should be useful to study the pathways and significance of these signs.
Revista …, 1997
... MEDICINA (Buenos Aires) 1997; 57 (Supl I): 93-100 TOXICOLOGÍA PRECLÍNICA DE BISFOSFONATOS NÉL... more ... MEDICINA (Buenos Aires) 1997; 57 (Supl I): 93-100 TOXICOLOGÍA PRECLÍNICA DE BISFOSFONATOS NÉLIDA MONDELO1, VIRGINIA A. PELUFFO1 ... animales normales sino en situaciones particulares con elevado recambio óseo, adecuando las dosis de manera de regular ...
Archives internationales de pharmacodynamie et de thérapie
A series of 1-alkylsulfonylaryl-1,4-benzodiazepine derivatives were synthesized and assayed for t... more A series of 1-alkylsulfonylaryl-1,4-benzodiazepine derivatives were synthesized and assayed for their pharmacological profile. All the compounds tested exhibited a competitive antagonism of 3H-diazepam binding in cerebellum, cerebrum and submaxillary gland. Compound II (rec. INN tolufazepam) had a Ki of 12.7 nM in cerebrum and 400 nM in the submaxillary gland. It was very potent in preventing convulsions elicited by pentylenetetrazol (ED50 p.o.: 16.5 and ED50 i.v.: 20 mg/kg). This anticonvulsant action was suppressed by previous administration of Ro 15-1788. Compound II was also active in inhibiting suppressive behaviour in the test of Vogel. This compound has a relative low hypnogenic activity as well as a low potency to produce motor incoordination. Our results show that tolufazepam has a potential clinical usefulness.
Int. Journal of Clinical Pharmacology and Therapeutics, 2022
BACKGROUND A fixed-dose combination (FDC) of candesartan cilexetil, hydrochlorothiazide and rosuv... more BACKGROUND A fixed-dose combination (FDC) of candesartan cilexetil, hydrochlorothiazide and rosuvastatin (CC/HCTZ/RSV) has been developed to enhance patient compliance in the primary prevention of cardiovascular diseases. OBJECTIVE To evaluate if the combination of the product components in the new FDC capsule formulation affects their respective pharmacokinetic and in vitro dissolution patterns. MATERIALS AND METHODS In vitro dissolution profiles were compared in USP-43 and in biorelevant dissolution media. In vivo comparisons were obtained in a randomized, open-label, single-dose, two-treatment, two-way crossover study in 24 healthy subjects. During each treatment period, subjects received the test formulation (FDC hard capsule containing CC/HCTZ/RSV) or the reference formulation (co-administration of a FDC CC/HCTZ tablet and a RSV tablet). Plasma samples were collected periodically over 48 hours post-dose. Safety and tolerability were assessed. RESULTS Dissolution profiles of all active drugs in the Test (capsule) and Reference Products (as tablets) were within the tolerance dissolution criteria of USP-43 conditions. HCTZ dissolution profiles were closely similar whereas those for RSV and CC did not match at specific pHs. In the pharmacokinetic study, the 90% confidence intervals (CIs) for the geometric least-square mean ratios of Cmax, AUC0-last, and AUC0-inf were 0.95 - 1.18, 0.95 - 1.15 and 0.95 - 1.13 (CC); 0.91 - 1.10, 0.96 - 1.08, and 0.96 - 1.09 (HCTZ) and 0.82 - 1.23, 0.81 - 1.13, and 0.82 - 1.12 (RSV), respectively. All adverse events were mild. CONCLUSION The new FDC product (Sinlip Prevent), a stable FDC hard capsule, was bioequivalent (similar pharmacokinetics) when compared to the co-administration of the components and may be considered as a suitable and simplified medication for cardiovascular disease management.
Journal of Bone and Mineral Research
Journal of musculoskeletal & neuronal interactions, 2013
Some pharmacologic effects on bone modeling may not be evident in studies of remodeling skeletons... more Some pharmacologic effects on bone modeling may not be evident in studies of remodeling skeletons. This study analyzes some effects of olpadronate on cortical bone modeling and post-yield properties in femurs diaphyses (virtually only-modeling bones) of young rats by mid-diaphyseal pQCT scans and bending tests. We studied 20/22 male/female animals traetad orally with olpadronate (45-90 mg/kg/d, 3 months) and 8/9 untreated controls. Both OPD doses enhanced diaphyseal cross-sectional moments of inertia (CSMI) with no change in cortical vBMD and elastic modulus. Yield stiffness and strength were mildly increased. Post-yield strength, deflection and energy absorption were strikingly enhanced. Ultimate strength was enhanced mainly because of effects on bone mass/geometry and post-yield properties. The large improvement of post-yield properties could be explained by improvements in bone geometry. Improvements in bone mass/geometry over weight-bearing needs suggest an enhanced modeling-rel...
Medicina, 1997
Bone mechanical competence (stiffness, strength) at organ level is determined by mechanical quali... more Bone mechanical competence (stiffness, strength) at organ level is determined by mechanical quality (intrinsic stiffness) and spatial distribution (macro-architecture) of bone material in cortical tissue (in every bone) and trabecular network (in vertebral bodies). These properties are inter-related and controlled according to mechanical usage by a feed-back mechanism known as mechanostat. Therefore, the effects on bone fragility of any treatment should be evaluated concerning the way they may have affected bone material or geometric properties as well as the mechanostatical interactions between them. Standard densitometry does not provide the necessary data, but some alternative methodologies (as peripheral quantitative computed tomography, pQCT) are being developed to complement or even substitute SPA, DPA or DXA determinations. Bisphosphonate (BP) effects on bone biomechanics have been studied only in animal models. Many sources of variation of results (type of compound, dose, mo...
Medicina, 1997
Ovariectomy and immobilization in rats have demonstrated to be useful models for osteopenia and t... more Ovariectomy and immobilization in rats have demonstrated to be useful models for osteopenia and they are considered to mimic some aspects of human osteoporosis associated with a deficit of ovarian hormones and the absence of mechanical function (disuse of the bone). Pamidronate (APD) and Olpadronate (OLPA), a new dimethylated aminobisphosphonate, on a continuous oral scheme (APD: 8 and OLPA: 0.8 mg/kg/day) or on an intermittent parenteral scheme (APD: 1.25 and OLPA: 0.075 mg/kg every 15 days) did effectively prevent the trabecular bone loss caused by immobilization (unilateral sciaticectomy), by lack of ovarian stimuli (bilateral ovariectomy) or by both approaches. There were no signs of deterioration in the cortical bone mass. In a model of preestablished osteopenia, caused by estrogen deprivation, OLPA stopped the progression of the bone mass loss (0.5 mg/kg/i.v. every 15 days) and restored (0.30-0.60 mg/kg/i.v. every 15 days) the bone mineral density which had been affected (trab...
Bone and Mineral, 1992
Blood and urine biomarkers of bone metabolism reflect Fort&ion Rotchild, laboratoire Ciba.France.... more Blood and urine biomarkers of bone metabolism reflect Fort&ion Rotchild, laboratoire Ciba.France. several different aspects of bone formation and resorption. The aim of thia study in to examine the Ninety one women were enrolled in a prospective trial for relative value of several bone markers of bone formation prevention of postmenopausal bone loss comparing calcium and resorption in relation to bone ma88 and its rate Of and hormonal treatment during 2 years. Inclusion criterion was lows in estrogen replete and deficient women, in black
Bone and Mineral, 1992
Blood and urine biomarkers of bone metabolism reflect Fort&ion Rotchild, laboratoire Ciba.France.... more Blood and urine biomarkers of bone metabolism reflect Fort&ion Rotchild, laboratoire Ciba.France. several different aspects of bone formation and resorption. The aim of thia study in to examine the Ninety one women were enrolled in a prospective trial for relative value of several bone markers of bone formation prevention of postmenopausal bone loss comparing calcium and resorption in relation to bone ma88 and its rate Of and hormonal treatment during 2 years. Inclusion criterion was lows in estrogen replete and deficient women, in black
Tumor Biology, 1999
Paraneoplastic syndromes are rarely described in animal models. It may be useful to have a suitab... more Paraneoplastic syndromes are rarely described in animal models. It may be useful to have a suitable experimental model to study the mechanisms by which they are produced. In this study, we describe a murine lung adenocarcinoma, P07, which presents hypercalcemia, leukocytosis and cachexia. We determined the presence of PTHrP in plasma as well as GM-CSF produced by P07 cells. TNF-alpha, which is responsible for cachexia, could neither be detected in serum nor in P07 cell supernatants. We conclude that this model, which shows paraneoplastic syndromes similar to those of lung tumor patients, should be useful to study the pathways and significance of these signs.
Oncology Reports, 2001
The purpose of this study was to investigate if specific immune responses were present in mice be... more The purpose of this study was to investigate if specific immune responses were present in mice bearing a lung adenocarcinoma that presents paraneoplastic syndromes during tumor evolution. Leukocytosis, mainly due to polymorphonuclear leukocytes, was found from day 15 of tumor growth. Delayed type hypersensitivity response and increased interleukin-6 (IL-6) serum levels were observed along tumor growth. Concomitant immunity, specific rejection of a second inoculum and in vitro specific cytotoxicity occurred at 20 days of implant. In advanced stages of tumor evolution impaired cytotoxicity, accompanied by a great increase of IL-6 in serum, were observed. Role of polymorphonuclear leukocytes and IL-6 overproduction as responsible for immune dysregulation and paraneoplastic syndromes are discussed.
Journal of Bone and Mineral Research, 2009
A compensation for differences in bone material qualtiy by bone geometric properties in femora fr... more A compensation for differences in bone material qualtiy by bone geometric properties in femora from two different strains of rats was previously shown by us. A feedback mechanism controlling the mechanical properties of the integrated bones was then proposed, in accordance with Frost's mechanostat theory. Evidence of such a system is now offered by the finding of a negative correlation between the modeling-dependent cross-sectional architecture (moment of inertia) and the mineral-dependent stiffness (elastic modulus) of bone material in the femoral diaphyses of 45 normal Wistar rats of different sexes, ages, and sizes. The strength and stiffness of the integrated diaphyses were found to depend on both cross-sectional inertia and body weight, not on bone mineral density. These findings are interpreted as supporting the hypothesis that the architectural efficiency of diaphyseal cross-sectional design resulting from the spatial orientation of bone modeling during growth is optimized as a function of the body weight-dependent bone strain history, within the constraints imposed by bone stiffness. Results suggest a modulating role of biomass, related to the system set point determination, and explain the usually observed lack of a direct correlation between mineral density and strength or stiffness of long bones in studies of geometrically inhomogeneous populations.
Tumor Biology, 1999
Paraneoplastic syndromes are rarely described in animal models. It may be useful to have a suitab... more Paraneoplastic syndromes are rarely described in animal models. It may be useful to have a suitable experimental model to study the mechanisms by which they are produced. In this study, we describe a murine lung adenocarcinoma, P07, which presents hypercalcemia, leukocytosis and cachexia. We determined the presence of PTHrP in plasma as well as GM-CSF produced by P07 cells. TNF-alpha, which is responsible for cachexia, could neither be detected in serum nor in P07 cell supernatants. We conclude that this model, which shows paraneoplastic syndromes similar to those of lung tumor patients, should be useful to study the pathways and significance of these signs.
Revista …, 1997
... MEDICINA (Buenos Aires) 1997; 57 (Supl I): 93-100 TOXICOLOGÍA PRECLÍNICA DE BISFOSFONATOS NÉL... more ... MEDICINA (Buenos Aires) 1997; 57 (Supl I): 93-100 TOXICOLOGÍA PRECLÍNICA DE BISFOSFONATOS NÉLIDA MONDELO1, VIRGINIA A. PELUFFO1 ... animales normales sino en situaciones particulares con elevado recambio óseo, adecuando las dosis de manera de regular ...
Archives internationales de pharmacodynamie et de thérapie
A series of 1-alkylsulfonylaryl-1,4-benzodiazepine derivatives were synthesized and assayed for t... more A series of 1-alkylsulfonylaryl-1,4-benzodiazepine derivatives were synthesized and assayed for their pharmacological profile. All the compounds tested exhibited a competitive antagonism of 3H-diazepam binding in cerebellum, cerebrum and submaxillary gland. Compound II (rec. INN tolufazepam) had a Ki of 12.7 nM in cerebrum and 400 nM in the submaxillary gland. It was very potent in preventing convulsions elicited by pentylenetetrazol (ED50 p.o.: 16.5 and ED50 i.v.: 20 mg/kg). This anticonvulsant action was suppressed by previous administration of Ro 15-1788. Compound II was also active in inhibiting suppressive behaviour in the test of Vogel. This compound has a relative low hypnogenic activity as well as a low potency to produce motor incoordination. Our results show that tolufazepam has a potential clinical usefulness.
Int. Journal of Clinical Pharmacology and Therapeutics, 2022
BACKGROUND A fixed-dose combination (FDC) of candesartan cilexetil, hydrochlorothiazide and rosuv... more BACKGROUND A fixed-dose combination (FDC) of candesartan cilexetil, hydrochlorothiazide and rosuvastatin (CC/HCTZ/RSV) has been developed to enhance patient compliance in the primary prevention of cardiovascular diseases. OBJECTIVE To evaluate if the combination of the product components in the new FDC capsule formulation affects their respective pharmacokinetic and in vitro dissolution patterns. MATERIALS AND METHODS In vitro dissolution profiles were compared in USP-43 and in biorelevant dissolution media. In vivo comparisons were obtained in a randomized, open-label, single-dose, two-treatment, two-way crossover study in 24 healthy subjects. During each treatment period, subjects received the test formulation (FDC hard capsule containing CC/HCTZ/RSV) or the reference formulation (co-administration of a FDC CC/HCTZ tablet and a RSV tablet). Plasma samples were collected periodically over 48 hours post-dose. Safety and tolerability were assessed. RESULTS Dissolution profiles of all active drugs in the Test (capsule) and Reference Products (as tablets) were within the tolerance dissolution criteria of USP-43 conditions. HCTZ dissolution profiles were closely similar whereas those for RSV and CC did not match at specific pHs. In the pharmacokinetic study, the 90% confidence intervals (CIs) for the geometric least-square mean ratios of Cmax, AUC0-last, and AUC0-inf were 0.95 - 1.18, 0.95 - 1.15 and 0.95 - 1.13 (CC); 0.91 - 1.10, 0.96 - 1.08, and 0.96 - 1.09 (HCTZ) and 0.82 - 1.23, 0.81 - 1.13, and 0.82 - 1.12 (RSV), respectively. All adverse events were mild. CONCLUSION The new FDC product (Sinlip Prevent), a stable FDC hard capsule, was bioequivalent (similar pharmacokinetics) when compared to the co-administration of the components and may be considered as a suitable and simplified medication for cardiovascular disease management.
Journal of Bone and Mineral Research
Journal of musculoskeletal & neuronal interactions, 2013
Some pharmacologic effects on bone modeling may not be evident in studies of remodeling skeletons... more Some pharmacologic effects on bone modeling may not be evident in studies of remodeling skeletons. This study analyzes some effects of olpadronate on cortical bone modeling and post-yield properties in femurs diaphyses (virtually only-modeling bones) of young rats by mid-diaphyseal pQCT scans and bending tests. We studied 20/22 male/female animals traetad orally with olpadronate (45-90 mg/kg/d, 3 months) and 8/9 untreated controls. Both OPD doses enhanced diaphyseal cross-sectional moments of inertia (CSMI) with no change in cortical vBMD and elastic modulus. Yield stiffness and strength were mildly increased. Post-yield strength, deflection and energy absorption were strikingly enhanced. Ultimate strength was enhanced mainly because of effects on bone mass/geometry and post-yield properties. The large improvement of post-yield properties could be explained by improvements in bone geometry. Improvements in bone mass/geometry over weight-bearing needs suggest an enhanced modeling-rel...
Medicina, 1997
Bone mechanical competence (stiffness, strength) at organ level is determined by mechanical quali... more Bone mechanical competence (stiffness, strength) at organ level is determined by mechanical quality (intrinsic stiffness) and spatial distribution (macro-architecture) of bone material in cortical tissue (in every bone) and trabecular network (in vertebral bodies). These properties are inter-related and controlled according to mechanical usage by a feed-back mechanism known as mechanostat. Therefore, the effects on bone fragility of any treatment should be evaluated concerning the way they may have affected bone material or geometric properties as well as the mechanostatical interactions between them. Standard densitometry does not provide the necessary data, but some alternative methodologies (as peripheral quantitative computed tomography, pQCT) are being developed to complement or even substitute SPA, DPA or DXA determinations. Bisphosphonate (BP) effects on bone biomechanics have been studied only in animal models. Many sources of variation of results (type of compound, dose, mo...
Medicina, 1997
Ovariectomy and immobilization in rats have demonstrated to be useful models for osteopenia and t... more Ovariectomy and immobilization in rats have demonstrated to be useful models for osteopenia and they are considered to mimic some aspects of human osteoporosis associated with a deficit of ovarian hormones and the absence of mechanical function (disuse of the bone). Pamidronate (APD) and Olpadronate (OLPA), a new dimethylated aminobisphosphonate, on a continuous oral scheme (APD: 8 and OLPA: 0.8 mg/kg/day) or on an intermittent parenteral scheme (APD: 1.25 and OLPA: 0.075 mg/kg every 15 days) did effectively prevent the trabecular bone loss caused by immobilization (unilateral sciaticectomy), by lack of ovarian stimuli (bilateral ovariectomy) or by both approaches. There were no signs of deterioration in the cortical bone mass. In a model of preestablished osteopenia, caused by estrogen deprivation, OLPA stopped the progression of the bone mass loss (0.5 mg/kg/i.v. every 15 days) and restored (0.30-0.60 mg/kg/i.v. every 15 days) the bone mineral density which had been affected (trab...
Bone and Mineral, 1992
Blood and urine biomarkers of bone metabolism reflect Fort&ion Rotchild, laboratoire Ciba.France.... more Blood and urine biomarkers of bone metabolism reflect Fort&ion Rotchild, laboratoire Ciba.France. several different aspects of bone formation and resorption. The aim of thia study in to examine the Ninety one women were enrolled in a prospective trial for relative value of several bone markers of bone formation prevention of postmenopausal bone loss comparing calcium and resorption in relation to bone ma88 and its rate Of and hormonal treatment during 2 years. Inclusion criterion was lows in estrogen replete and deficient women, in black
Bone and Mineral, 1992
Blood and urine biomarkers of bone metabolism reflect Fort&ion Rotchild, laboratoire Ciba.France.... more Blood and urine biomarkers of bone metabolism reflect Fort&ion Rotchild, laboratoire Ciba.France. several different aspects of bone formation and resorption. The aim of thia study in to examine the Ninety one women were enrolled in a prospective trial for relative value of several bone markers of bone formation prevention of postmenopausal bone loss comparing calcium and resorption in relation to bone ma88 and its rate Of and hormonal treatment during 2 years. Inclusion criterion was lows in estrogen replete and deficient women, in black
Tumor Biology, 1999
Paraneoplastic syndromes are rarely described in animal models. It may be useful to have a suitab... more Paraneoplastic syndromes are rarely described in animal models. It may be useful to have a suitable experimental model to study the mechanisms by which they are produced. In this study, we describe a murine lung adenocarcinoma, P07, which presents hypercalcemia, leukocytosis and cachexia. We determined the presence of PTHrP in plasma as well as GM-CSF produced by P07 cells. TNF-alpha, which is responsible for cachexia, could neither be detected in serum nor in P07 cell supernatants. We conclude that this model, which shows paraneoplastic syndromes similar to those of lung tumor patients, should be useful to study the pathways and significance of these signs.
Oncology Reports, 2001
The purpose of this study was to investigate if specific immune responses were present in mice be... more The purpose of this study was to investigate if specific immune responses were present in mice bearing a lung adenocarcinoma that presents paraneoplastic syndromes during tumor evolution. Leukocytosis, mainly due to polymorphonuclear leukocytes, was found from day 15 of tumor growth. Delayed type hypersensitivity response and increased interleukin-6 (IL-6) serum levels were observed along tumor growth. Concomitant immunity, specific rejection of a second inoculum and in vitro specific cytotoxicity occurred at 20 days of implant. In advanced stages of tumor evolution impaired cytotoxicity, accompanied by a great increase of IL-6 in serum, were observed. Role of polymorphonuclear leukocytes and IL-6 overproduction as responsible for immune dysregulation and paraneoplastic syndromes are discussed.
Journal of Bone and Mineral Research, 2009
A compensation for differences in bone material qualtiy by bone geometric properties in femora fr... more A compensation for differences in bone material qualtiy by bone geometric properties in femora from two different strains of rats was previously shown by us. A feedback mechanism controlling the mechanical properties of the integrated bones was then proposed, in accordance with Frost's mechanostat theory. Evidence of such a system is now offered by the finding of a negative correlation between the modeling-dependent cross-sectional architecture (moment of inertia) and the mineral-dependent stiffness (elastic modulus) of bone material in the femoral diaphyses of 45 normal Wistar rats of different sexes, ages, and sizes. The strength and stiffness of the integrated diaphyses were found to depend on both cross-sectional inertia and body weight, not on bone mineral density. These findings are interpreted as supporting the hypothesis that the architectural efficiency of diaphyseal cross-sectional design resulting from the spatial orientation of bone modeling during growth is optimized as a function of the body weight-dependent bone strain history, within the constraints imposed by bone stiffness. Results suggest a modulating role of biomass, related to the system set point determination, and explain the usually observed lack of a direct correlation between mineral density and strength or stiffness of long bones in studies of geometrically inhomogeneous populations.