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Biomedical subjects

C E Bozzini

Publications and source records attributed to C E Bozzini.

At least 19 recordsLinked to original sources
PubMed2002

Dynamics of recovery of morphometrical variables and pQCT-derived cortical bone properties after a short-term protein restriction in maturing rats.

Severe protein restriction during the post-weaning period in the rat markedly reduces femoral bone mass and produces a number of alterations in the shaft biomechanical properties. Body weight and femur length show an immediate and complete catch-up during nutritional rehabilitation. The aim of the present investigation was to assess whether the accelerated bone growth that occurs during protein rehabilitation is accompanied by recovery of cortical bone properties. The dynamics of the recovery of both material and geometric properties were thus evaluated on the femoral diaphyses in 45-day old female rats after a 10-day period of dietary protein restriction by peripheral quantitative computed tomography (pQCT). Protein starvation led to marked reduction of both body weight and femoral length (37% and 14% at day 10, respectively) which showed a complete catch-up after 30 d of protein refeeding. Protein restriction was associated with the interruption of the natural increase in cortical area (CtCSA), volumetric cortical bone mineral content (vCtBMC) and volumetric cortical bone mineral density (vCtBMD) which were 19.7, 25.8, and 14%, respectively, in malnourished than in control rats at the end of the protein starvation period. These parameters recovered completely during protein refeeding. Treatment also reduced by 30% both rectangular (xCSMI) and polar (pCSMI) moments of inertia. Although an improvement of these architectural indicators occurred with time, an approximately 20% deficit was still present at the end of the observation period (70 d), as was the bone strength index (BSI). It is concluded that protein restriction affected the adaptation of diaphyseal design which should reduce the mechanical competence of the femoral diaphysis because of an inadequate architectural distribution of cortical bone, and that the alteration did not show complete catch-up during the studied period.

Aging↗
PubMed2001

Prolonged exposure to hypobaric hypoxia transiently reduces GABA(A) receptor number in mice cerebral cortex.

The central nervous system is severely affected by hypoxic conditions, which produce alterations in neural cytoarchitecture and neurotransmission, resulting in a variety of neuropathological conditions such as convulsive states, neurobehavioral impairment and motor CNS alterations. Some of the neuropathologies observed in hypobaric hypoxia, corresponding to high altitude conditions, have been correlated with a loss of balance between excitatory and inhibitory neurotransmission, produced by alterations in glutamatergic and GABAergic receptors. In the present work, we have studied the effect of chronic hypobaric hypoxia (506 hPa, 18 h/day x 21 days) applied to adult male mice on GABA(A) receptors from cerebral cortex, to determine whether hypoxic exposure may irreversibly affect central inhibitory neurotransmission. Saturation curves for [3H]GABA specifically bound to GABA(A) receptors in isolated synaptic membranes showed a 30% decrease in maximal binding capacity after hypoxic exposure (Bmax control, 4.70+/-0.19, hypoxic, 3.33+/-0.10 pmol/mg protein), with no effect on GABA binding sites affinity (Kd control: 159.3+/-13.3 nM, hypoxic: 164.2+/-15.1 nM). Decreased B(max) values were observed up to the 10th post-hypoxic day, returning to control values by the 15th post-hypoxic day. Pharmacological properties of GABA(A) receptor were also affected by hypoxic exposure, with a 45 to 51% increase in the maximal effect by positive allosteric modulators (pentobarbital and 5alpha-pregnan-3alpha-ol-20-one). We conclude that long-term hypoxia produces a significant but reversible reduction on GABA binding to GABA(A) receptor sites in cerebral cortex, which may reflect an adaptive response to this sustained pathophysiological state.

Animals↗
PubMed1999

Catch-up in mandibular growth after short-term dietary protein restriction in rats during the post-weaning period.

Catch-up growth has been defined as growth with a velocity above the statistical limits of normality for age during a defined period of time which follows a period of impaired growth. Since no data are available on catch-up in mandibular growth, the present study was designed to estimate the dynamics of the mandibular size after short-term dietary protein restriction in rats during the post-weaning period. Weanling male rats, 22 d of age, were divided into two groups, control (C) and experimental (E). E rats were fed a protein-free diet during the first 10 d; from this time on, they were placed on a 20% protein diet, as were C rats during the entire experimental period, which lasted 70 d. Five rats from both groups were randomly selected every 10 d and sacrificed. Mandibular growth was estimated directly on the right mandible by measuring several dimensions (mandibular area, base length, mandibular height, mandibular length, alveolar length and incisor alveolar process length). Alveolar and incisor alveolar process lengths did not change with age or dietary protein. All other dimensions increased with age and were thus negatively affected by protein restriction. After growth restriction ceased, the rate of increase of all affected dimensions was above normal values and deficits were swiftly eliminated. Since age-independent dimensions compose roughly the anterior portion of the mandible, this portion of the bone was not affected by protein restriction. It was, thus, the posterior part of the mandible which stopped growth during the nutritional insult and showed catch-up during nutritional rehabilitation. In summary, the rat mandible has a high potential for catch-up during the post-weaning period, showing the ability to achieve complete catch-up in about 30 d.

Age Factors↗
PubMed1999

Erythropoietin assay in mice made polycythemic by transfusion of heterologous red cells.

A simple in vivo bioassay suitable for routine testing of quality control of recombinant human erythropoietin (rHu-EPO) analogues was developed. Mice made polycythemic by intraperitoneal injection of 1.2 ml of a 80% suspension of heterologous (rat) red cells were used as assay animals and splenic 59Fe uptake as expression of the response to rHu-EPO. The assay took three days and the following schedule is proposed: 1) intraperitoneal injection of 1.2 ml of washed packed red cells obtained from donor rats, 2) subcutaneous injection of test material 4-5 h after transfusion, 3) intravenous administration of 59Fe tracer 48 h later, and 4) determination of splenic isotope uptake 6 h after injection. This method for the in vivo bioassay of rHu-EPO analogues is an economical and reliable alternative to the existing bioassays of the hormone.

Animals↗
PubMed1998

Plasma disappearance of exogenous erythropoietin in mice under different experimental conditions.

Erythropoietin (EPO) is a glycoprotein hormone produced primarily in the kidneys and to a lesser extent in the liver that regulates red cell production. Most of the studies conducted in experimental animals to assess the role of EPO in the regulation of erythropoiesis were performed in mouse models. However, little is known about the in vivo metabolism of the hormone in this species. The present study was thus undertaken to measure the plasma tl/2 of radiolabeled recombinant human EPO (rh-EPO) in normal mice as well as in mice with altered erythrocyte production rates (EPR), plasma EPO (pEPO) titer, marrow responsiveness, red cell volume, or liver function. Adult CF-1 mice of both sexes were used throughout. For the EPO life-span studies, 30 mice in each experiment were intravenously injected with 600,000 cpm of 125l-rh-EPO and bled by cardiac puncture in groups of five every hour for 6 h. Trichloroacetic acid (TCA) was added to each plasma sample and the radioactivity in the precipitate measured in a gamma-counter. EPO, pEPO, marrow responsiveness, or red cell volume were altered by either injections of rh-EPO, 5-fluorouracil, or phenylhydrazine, or by bleeding, or red cell transfusion. Liver function was altered by CI4C administration. In the normal groups of mice, the estimated tl/2 was 182.75+/-14.4 (SEM) min. The estimated tl/2 of the other experimental groups was not significantly different from normal. These results, therefore, strongly suggest that the clearance rate of EPO in mice is not subjected to physiologic regulation and that pEPO titer can be really taken as the reflection of the EPO production rate, at least in the experimental conditions reported here.

Animals↗
PubMed1997

Influence of bisphosphonate on the negative erythropoietic effects of uranyl nitrate.

Uranium salts, such as uranyl nitrate, induce severe renal dysfunction and tubular necrosis and a significant impairment of both oxygen dependent erythropoietin production and response to recombinant human erythropoietin. All effects are transient and reach maximal severity on the 7th day post injection. We investigated the effects of ethane 1-hydroxy-1, 1-bisphosphonate, which counteracts the inhibitory effect of uranyl nitrate on bone formation, on the negative erythropoietic effects of uranyl nitrate. Adult female Wistar rats received 1 mg/kg body weight of uranyl acetate by the i.v. route. Ethane 1-hydroxy-1,1-bisphosphonate was injected simultaneously at a dose of 7.5 mg/kg by the same route. Seven days after drug injections, plasma erythropoietin was estimated after hypobaric hypoxemia or cobalt chloride administration. The response to exogenous erythropoietin was also measured in uranyl nitrate- and/or ethane 1-hydroxy-1,1-bisphosphonate-injected rats made polycythemic by transfusion. The erythroid response was quantitated in terms of red blood cell 59iron uptake. Ethane 1-hydroxy-1, 1-bisphosphonate counteracted the effect of uranyl nitrate on oxygen-dependent and cobalt-dependent erythropoietin production, but did not correct the right shift of the dose-response relationship for exogenous erythropoietin induced by uranyl nitrate in the polycythemic rat.

Animals↗
PubMed1997

Unexpected hypoxia-dependent erythropoietin secretion during experimental conditions not affecting tissue oxygen supply/demand ratio.

Although a great deal of evidence supports the hypothesis that plasma erythropoietin (EPO) levels of mammals are related to the oxygen supply to the tissues relative to their oxygen needs, several observation millitate against its inherent simplicity. This study presents our results obtained from in vivo experiments that suggest that hypoxia-dependent EPO production can be altered by conditions which apparently do not modify the tissue oxygen supply/demand ratio. Hypoxia-dependent EPO production rate (EPO-PR), derived from plasma EPO titers and plasma EPO half-lives, were estimated in both transfused-polycythemic and normocythemic mouse models subjected to different treatments. From calculations of the O2 carrying capacity of blood and body O2 consumption, it was assumed that the tissue supply/demand ratios were similar in both experimental and control mice of the same model at the time of induction of EPO production. The following observations were worth noting: (1) EPO-PRs in transfused polycythemic mice whose erythropoietic rates were stimulated by intermittent exposure to hypobaria (0.5 atm, 18 hr/day x 3 weeks), phenylhydrazine administration (40 mg/kg at weekly intervals x 3 weeks) or repeated rh-EPO injections (1500 U/kg 3 times a week x 3 weeks) before transfusion were more than five times high than in comparabily polycythemic mice whose erythropoietic rates were not stimulated previously; and (2) EPO-PR in response to hypobaric hypoxia was 2.08 times normal in normocythemic mice with cyclophosphamide (100 mg/kg) induced depression of erythropoiesis, and 0.33 times normal in normocythemic mice with rh-EPO (400 U/kg x 2) induced enhancement of erythropoiesis. Although the results obtained in polycythemic mice are difficult to explain, those from normocythemic mice suggest the existence of a feedback mechanism between EPO-responsive cells and EPO-producing cells. Both demonstrate the existence of experimental conditions in which modulation of the hypoxia-dependent expression of the EPO gene appears to occur. This modulation would be dependent on factors other than oxygen.

Animals↗
PubMed1997

Unmodified erythropoietic response to a beta adrenergic agonist in hypothyroid mice.

beta-adrenergic agonists are able to increase erythropoiesis in the polycythemic mouse model by possibly increasing erythropoietin secretion. Since a great deal of evidence indicates that the actions of thyroid hormones and catecholamines are intimately interrelated, the present study was designed to estimate the erythropoietic response to isoproterenol, a very well-known beta-adrenergic agonist, in hypothyroid mice. Adult male CF-1 mice, maintained on a standard rodent chow and water (euthyroid) or 0.1% propylthiouracil (PTU) solution (hypothyroid) ad libitum during 37 days. Plasma T4 concentration was 1.75 +/- 0.25 micrograms/ml in euthyroid and < 1.0 microgram/ml in hypothyroid mice at this time. Mice were transfused with 1.0 ml of packed homologous red cells and the erythropoietic effect of graded doses (50, 500 and 5000 micrograms/kg) were tested by the RBC-59Fe incorporation method. No statistically significant differences (unpaired t test) were found between euthyroid and hypothyroid mice. Hypothyroidism, therefore, does not affect beta-adrenergic agonist-induced erythropoietin secretion in the present experimental conditions.

Adrenergic beta-Agonists↗
PubMed1995

Dexamethasone effects on mechanical, geometric and densitometric properties of rat femur diaphyses as described by peripheral quantitative computerized tomography and bending tests.

In previous studies with cortisol, betamethasone and oxazacort we attributed glucocorticoid effects on bone biomechanics to changes in bone mass and geometry rather than to an action on bone material properties. In this experiment, groups of 7 rats each received subcutaneous doses of 15.6, 31.2, 62.5, 125, 250, 500 or 1000 micrograms/kg per day of dexamethasone (DMS) and an additional 14 animals were controlled untreated for 4 weeks. Their fresh femurs were then scanned by peripheral quantitative computerized tomography (pQCT; XCT-960, Stratec, Germany) at the midshaft and submitted to three-point bending tests. In consonance with our earlier investigations, a significant, log-dose-related reduction in bone load-bearing capacity was observed, associated with an impairment in bone geometric properties (cross-sectional area and moment of inertia) and in body weight gain. However, the pQCT-assessed volumetric mineral density of cortical bone (vCtBMD; regarded as a material quality indicator in terms of mineralization) was significantly reduced by DMS following a dose-response relationship. Furthermore, a direct association was detected between vCtBMD and diaphyseal load-bearing capacity and stiffness. In contrast with our previous approach, data suggests that, apart from changes in bone geometric properties, glucocorticoid effects on bone material quality--as assessed by vCtBMD changes in this study--seem also to play a significant role in the determination of their biomechanical consequences.

Animals↗
PubMed1995

Body weight loss during acute hypoxia: effects of increased convective oxygen transport or previous acclimation.

Body weight loss and growth retardation occur in rats exposed to simulated high altitude, which may be related to the hypoxemia-induced reduction in the convective oxygen transport (COT). The present study was thus performed to determine whether transfusion polycythemia, increased affinity of hemoglobin for oxygen, or previous acclimation to hypobaria (factors that increase COT) are able to counteract its effect on body weight during the early period of exposure, which appears to be a suitable parameter to test the effectiveness of acclimatization. Polycythemia was induced in weanling rats by two ip injections of 2.5 ml/100 g b.wt of packed homologous red cells. The rise in hemoglobin O2 affinity was brought about in adult rats by giving them 0.5 g/dl sodium cyanate in the drinking water for 3 weeks. A lower body weight loss during the early period of exposure to hypobaria was seen in treated rats than in controls. However, body weight loss was still important, which would indicate that compensation was probably not complete. When growing rats were acclimated to simulated altitude, a sudden increase in body weight was observed when they were brought back to ground levels. When animals were taken to altitude again, they lost weight at a rate not significantly different to that found in non-acclimated ones. The results obtained indicate that treatments do not prevent the studied effect of hypoxia and suggest that hypophagia and the resultant initial body weight loss and secondary depression of body growth could be considered as protective mechanisms against the environmental challenge, although further investigation will be necessary to confirm the hypothesis.

Acclimatization↗
PubMed1994

Inhibitory effect of an alpha 1-adrenergic antagonist on erythropoiesis in normoxic or hypoxic mice.

The present study was undertaken to assess the effect of prazosin, a selective postsynaptic alpha 1-adrenergic receptor blocking agent, on normoxic and hypoxic mice, in order to evaluate experimentally its use in the treatment of the excessive erythrocytosis that characterizes chronic mountain sickness. The drug, injected intraperitoneally to adult mice at a dose of 400 micrograms/kg per day, induced a significant depression of the rate or erythropoiesis, as measured by red blood cell 59iron uptake, with a decrease in the hematocrit from the 3rd day. The drug also inhibited the oxygen-dependent secretion of erythropoietin (estimated by the plasma immunoreactive hormone concentration) in hypoxemic mice when injected between 0 and 2 h after initiation of the hypoxic stimulation. When injected daily into mice exposed to intermittent hypobaric hypoxia, prazosin limited the degree of polycythemia or induced a sustained decrease in the hematocrit when polycythemia was already present due to previous exposure. It is postulated that the drug, by reducing the peripheral vascular resistance seen during hypoxia, could increase renal blood flow, thus improving the renal oxygen supply and partially restoring the imbalance between gas supply and demand, which drives erythropoietin formation.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1994

Additive effects of dietary protein and energy deficiencies on mandibular growth in the weanling rat.

Dietary protein restriction adversely affects mandibular growth in the weanling rat. Protein deficiency is usually accompanied by reduced food intake which, in turn, induces energy deficiency. The present study was thus designed to dissociate the effects of dietary protein and energy deficiencies on the growth of the mandible in rapidly growing rats. Four groups of Sprague-Dawley rats aged 30 days were fed a normal diet, a low-energy diet, a low protein diet, and a low-protein and low-energy diet for 20 days. Rats were sacrificed at the end of experimental period and body weight and mandibular dimensions were recorded to evaluate body growth and mandibular growth. The growth of the mandible was affected almost in the same order of magnitude by both protein and energy restrictions. When both were applied together, mandibular growth was even more severely affected. Two way analysis of variance revealed the absence of synergism between variables, indicating that the negative effects of dietary protein and energy restrictions on mandibular growth could be considered to be additive.

Analysis of Variance↗
PubMed1993

Impaired response of polycythemic mice to erythropoietin induced by protein starvation imposed after hormone administration.

The present study was performed to determine the stage of the erythropoietic pathway which is affected by starvation or protein deprivation and whose manifestation is a depressed response to exogenous erythropoietin (EPO). The response to recombinant human EPO was measured in post-hypoxic polycythemic mice by determination of 59Fe uptake into red cells, spleen and femur and/or erythroid colony forming units (CFU-E) and erythroid precursor cell concentrations in femoral marrow. Experimental mice were either starved or fed one of seven different diets whose protein (casein) content ranged from 0 to 20%. All diets were isocaloric. The response of mice maintained on the standard diet (Purina Lab chow) was taken as the normal one. Starvation during the 48-hour period immediately before EPO injection had no effect on the response to the hormone. Starvation, and protein deprivation to a lesser extent, during the 48-hour period following EPO, on the other hand, significantly reduced the response. There was a progressive increase in the response as the casein content of the diet was increased. A normal response was observed when dietary casein concentration was 10%. These findings indicate that nutritional deprivation or dietary protein alterations during the period immediately following EPO injection in polycythemic mice can have detrimental effects on the erythroid response in a model in which nutritional deprivation was relatively short and acute. They also indicate that the subnormal response is not due to a decreased size of the erythroid progenitor pool available for differentiation but to deficient rates of differentiation of erythropoietic units.

Animals↗
PubMed1993

Damage of tracer erythropoietin results in erroneous estimation of concentration in mouse submaxillary gland.

It has been previously reported that 1) plasma erythropoietin (Epo) titer during exposure to hypobaria is lower in nephrectomized rats and mice whose submaxillary glands (SMG) were either ablated or atrophied than in nephrectomized controls whose SMG were intact and 2) that the gland shows one of the highest levels of immunoreactive Epo (iEpo) in the body. The latter observation, however, was questioned recently when it was observed that SMG extracts degrade labeled Epo used as tracer antigen in the radioimmunoassay (RIA), thus giving invalid estimates of Epo. Since this interpretation was in turn questioned, the present study was conducted to obtain more information on the subject and make these conflicting points clear. Investigation of the reported/possible degradation of Epo by SMG homogenates was conducted via polyacrylamide gel electrophoresis followed by radioautography or by a RIA in solid phase in which there was no simultaneous incubation of the tracer antigen with the SMG homogenates. It was observed that 125I-labeled rhEpo was degraded when incubated with SMG homogenates. Degradation was rapid, being evident when incubation lasted 30 minutes, and occurred in the presence of a protease inhibitor. It showed a high degree of specificity since it did not occur when Epo was incubated with kidney homogenate or normal mouse serum. SMG homogenate did not degrade labeled thyrotrophic hormone and degraded alpha interferon (IFN-alpha) only partially. When estimates of iEpo in SMG homogenate were performed in conditions of simultaneous (SI-RIA) or nonsimultaneous (NSI-RIA) incubation of the homogenate with tracer Epo, it was observed that while estimates of Epo in plasma were similar in both types of RIA and somewhat higher in kidney homogenate in the SI-RIA than in the NSI-RIA, estimates of Epo in SMG were about 60 times higher in the former than in the latter. Therefore, it could be concluded that most of the Epo detected by standard RIA in SMG homogenate does not represent true Epo because of damage of tracer Epo which determines loss of the integrity of the RIA system.

Animals↗
PubMed1991

Additive effects of dietary protein and energy deficiencies on diaphysis and bone tissue of rat femurs as determined by bending tests.

The present study was designed to study the effects of diets moderately restricted in protein and/or carbohydrate derived calories on morphometric parameters (geometric properties) and mechanical performance of both diaphysis (structural properties) and cortical bone tissue (material properties) from growing rat femurs, as determined by bending tests at low strain rates. Male rats aged 30 days were divided in four groups, namely NN = normal protein and energy, NPLE = normal protein and low energy, LP = low protein and normal energy, and LPLE = low protein and low energy. Each group was fed on a corresponding diet for 20 days. Both body weight and femoral length were greater in NN and lower in LL than in LE and LP groups. Geometrical and structural variables (with the exception of wall/lumen ratio) grossly paralleled changes in body weight, while material properties showed independent and less significant changes. Therefore, the assayed levels of restriction of either plastic or energetic nutrients seemed to alter bone biomechanics proportionally to the way it affected bone growth.

Animals↗