Biomedical subjects

C E Bozzini

Publications and source records attributed to C E Bozzini.

At least 37 records · Page 2Linked to original sources

PubMed1991

Serum immunoreactive erythropoietin in high altitude natives with and without excessive erythrocytosis.

We report the estimation of blood hemoglobin (Hb), arterial blood oxygen saturation (SaO2), and serum immunoreactive erythropoietin (siEPO) in a group of Peruvian workers residing in Cerro de Pasco at 4300 m showing "excessive erythrocytosis" (EE, Monge's disease, chronic mountain sickness). These estimates were compared with those of humans residing either in Cerro de Pasco and showing "normal erythrocytosis" (NE) or in Lima (sea level, SL) to determine whether Hb and SaO2 are related to siEPO in high altitude (HA) natives with NE or EE. The three parameters showed statistically significant differences between HA and SL groups--the values in SL being lower. Significant differences were also found between NE and EE groups in Hb and SaO2. There was no statistical difference in siEPo between the two groups. The results indicate, therefore, that HA residents who develop EE are not distinguishable from residents who develop NE on the basis of estimates of siEPO. As a result, siEPO and Hb do not show a dose-response relationship in HA residents, and variation in EPO does not explain the striking variation in Hb at high altitudes.

Adult↗

PubMed1990

Depressed eruption rate of the rat maxillary incisor in a drug-induced uncompensated hemolytic state model.

Female rats weighing about 180 g were separated into two groups. One group (A) received phenylhydrazine (PHZ) every other day during three weeks (for induction of an uncompensated hemolytic state), while the control group (C) received saline. The evidence for the establishment of the uncompensated hemolytic state was obtained by hematocrit value, reticulocyte count, and red-cell-volume-59Fe uptake. Body-weight gain (which is a measure of overall body growth rate), body-length gain (which is a measure of longitudinal skeletal growth rate), food intake, and maxillary incisor eruption rate (ER) were significantly depressed in rats of group A during the PHZ-injection period, in relation to rats of group C. These results indicate that anemia and/or associated factors depress ER, along with body growth and skeletal growth.

Analysis of Variance↗

PubMed1990

Immunoreactive erythropoietin in rodent submaxillary gland. Autonomic control of exocrine secretion and factors influencing its concentration.

The SMG of mice and rats contain a heterologous group of biologically active factors. Some are well known, can be obtained at high purity and are well-characterized. There is strong evidence for the presence of others although they have not been purified. Finally, some of them are questionable and/or have not yet been characterized. EPO would be one of the factors whose presence in the SMG is strongly suspected, although its biological activity has not been demonstrated yet. Its presence in the gland, therefore, is only supported by radioimmunoassay data and immunocytochemical methods. Immunoreactive EPO is undetectable in the mouse SMG until the 30th day of postnatal life, increasing thereafter at a uniform rate and reaching adult levels by 50-60 days of age. The parallelism between its concentration in extracts of the gland, the size and relative proportion of GCT cells, could be accepted as indirect evidence for its localization in these cells. The rise in iEPO concentration in SMGs after androgen treatment, its fall following orchiectomy, and its reduction after duct ligation in proportion to the degree of degranulation of GCT cells lend support to the above hypothesis. Salivary secretions induced by either NE or ISO contain high levels of iEPO. A significant depletion of gland content is also observed. These two sets of data indicate that SMG exocrine iEPO secretion occurs and that this secretion is mediated by adrenergic receptors. The question whether the SMG also functions as an endocrine organ in relation to EPO can not be answered at present.

Age Factors↗

PubMed1990

Depressed plasma erythropoietin levels in rats with hemodynamically-mediated acute renal failure.

Adult female Wistar rats were injected with 125 mg/kg b.w. of human methemoglobin (M-Hb) in order to induce a first episode of hemodynamically-mediated acute renal failure (HMARF). Eleven days after the injection of M-Hb, other groups of rats received another equal dose of the drug in order to induce a second episode of HMARF. Evaluation of renal function, histopathology studies, and determinations of plasma and kidney erythropoietin (Epo) titers by radioimmunoassay in normoxic and hypoxic conditions were performed 1, 2, 3, 5 and 10 days after M-Hb administration. Treatment induced transient increases in plasma urea concentration, fractional sodium excretion, and urine volume, and significant depression in urine osmolality. In every case, the maximal effect of the first injection of M-Hb on the individual parameters was always greater than that of the second injection, and observed on the 5th post-injection day. Histologic sections showed interstitial cellular infiltration, desquamation of the proximal tubular epithelium and collapse or dilation of the tubular lumen. Treatment with M-Hb depressed Epo titers in both kidney homogenates and plasma in normoxic as well as hypoxic rats. Here again, the effect of the first injection of the drug was higher than that of the second one. These observations indicate that there is a negative correlation between kidney tubule injury and Epo production in normoxic and hypoxic conditions. The findings give support to the concept that Epo production is related to proximal tubular function.

Acute Kidney Injury↗

PubMed1989

The mechanism of the transient depression of the erythropoietic rate induced in the rat by a single injection of uranyl nitrate.

With the purpose of assessing the effect of uranyl nitrate (UN) on the rate of erythropoiesis, 1 mg/kg of the compound was injected iv to adult female Wistar rats. The dosing vehicle was injected into control animals. A single injection of UN induced a transient depression of the rate of red cell volume 59Fe uptake, which reached its lowest value (68% depression) by the seventh postinjection day. By 14 days, 59Fe incorporation had returned to normal. The amount of iron going to erythroid tissue per hour, reticulocyte count, and immunoreactive erythropoietin concentration in both plasma and kidney extracts were also significantly depressed in UN-treated rats in relation to these values in vehicle-injected rats by the seventh postinjection day. Dose-response curves for exogenous erythropoietin (Epo) performed in polycythemic intact and UN-treated rats 7 days after drug injection revealed a significant depression of the response in UN-injected animals. Moreover, bone marrow cells obtained from rats pretreated with UN formed a reduced number of erythroid colonies in vitro in response to Epo. Therefore, possible mechanisms for the observed transient depression in the rate of erythropoiesis associated with acute UN treatment include decreased Epo production and direct or indirect damage of erythroid progenitor cells.

Animals↗

PubMed1989

Enhanced effect of increased erythrocyte production rate on plasma erythropoietin levels of mice during subsequent exposure to hypobaria.

The present study was undertaken to determine plasma EPO levels in response to acute exposure to hypobaria in transfused-polycythemic mice previously exposed to different forms of erythropoietic stimulation. The erythrocyte production rate (EPR) was stimulated by one of the following conditions: (1) discontinuous exposure to 456 mb during 4 weeks, (2) one weekly injection of phenylhydrazine (PHZ) during 4 weeks for induction of a compensated hemolytic state, and 3) three weekly injections of rHuEPO at a dose level of 1500 U/Kg body weight for 4 weeks. Treated and control mice received different volumes of packed red cells in order to obtain hematocrit values around 65% in all groups. Mice from each group were exposed to 456 mb during 14 h, 4 days after transfusion. Mice were bled immediately through cardiac puncture after removal from the hypobaric chamber. Plasma EPO titer was estimated by radioimmunoassay. Two observations were worth noting: (1) plasma iEPO level was very low in mice with transfusion polycythemia exposed to hypobaria, the value of 12 +/- 1.3 mU/ml being significantly different from that of 180 +/- 18 mU/ml found in normocythemic mice similarly exposed, and (2) plasma iEPO levels during EPRs were previously stimulated by different conditions (hypobaria, PHZ and rHuEPO) were at least as high as those found in normocythemic mices similarly exposed. All these values were significantly higher than the value corresponding to polycythemic mice whose EPRs were not stimulated before exposure to hypobaria.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

The concentration of dietary casein required for normal mandibular growth in the rat.

To determine a suitable casein concentration for normal, undeformed mandibular growth, we placed weanling male rats on diets containing graded levels of casein between 0% and 30% for 19 days. Some weanlings were killed so that initial values could be established. Ten linear dimensions corresponding to the six skeletal units of the mandible were evaluated so that their growth rates at the end of the experimental period could be established. Other dimensions were also evaluated for study of the growth rate of the bone as a whole. The macroscopic growth of the mandible showed a sigmoidal relationship with dietary casein concentration, most of the measurements reaching a plateau at 20% casein. Within the skeletal units, four dimensions corresponding to the alveolar and symphyseal regions did not change with age and were not affected by the casein content of the diet. The remaining six dimensions-corresponding to condylar, coronoid, angular, and basal regions of the mandible-increased with age and were related positively to dietary casein concentration. Their growth patterns were not uniform, although all of them reached maximal values when the diet contained 20% casein. Therefore, deformation of the mandible appears to occur in rats fed diets with a casein concentration lower than 20%. It appears that a dietary casein concentration of 20% is required for normal, undeformed mandibular growth.

Animals↗

PubMed1989

Correlation between erythropoietic activity and body growth rate in hypertransfused polycythemic growing rats as the result of an erythropoietin-dependent operating mechanism.

The established relationship between erythropoietic activity and body growth rate in the polycythemic growing rat could be the result of either an erythropoietin (EPO)-dependent or an EPO-independent operating mechanism. The present study was thus undertaken to elucidate the nature of the aforementioned mechanism by assessing the ratio between plasma immunoreactive EPO (iEPO) concentration and erythropoietic activity in young hypertransfused rats for different body growth rates. Red blood cell (RBC)-59Fe uptake was about 75% in 21-day-old rats; it rapidly decreased with time when the animals were placed on a protein-free diet, approaching a level of about 1% by the 10th day of protein starvation. Over the same period plasma iEPO decreased from 55 mU/ml to 7 mU/ml. Body growth rate was 0. Following this "protein depletion period" the rats received diets containing different amounts of casein ("protein repletion period") added isocalorically to the protein-free diet to elicit a rise in body growth rate. Statistically significant relationships (p less than 0.001) were found between dietary casein concentration and body growth rate (r = 0.991), dietary casein concentration and RBC-59Fe uptake (r = 0.991), dietary casein concentration and plasma iEPO level (r = 0.992), body growth rate and RBC-59Fe (r = 0.986), and body growth rate and plasma iEPO level (r = 0.994) in hypertransfused polycythemic rats during the protein repletion period. These findings suggest that the correlation between erythropoietic activity and growth rate in the growing rat is the result of an erythropoietin-dependent operating mechanism, which appears to be independent of the ratio tissue oxygen supply/tissue oxygen demand.

Aging↗

PubMed1988

Biomechanical performance of diaphyseal shafts and bone tissue of femurs from protein-restricted rats.

The aim of this study was to define the biomechanical repercussion of a severe protein restriction on the shaft of long bones and on cortical bone tissue. Femurs from 9 rats fed a protein-free diet from the 30th to the 50th day of age showed a great reduction of bending strength and stiffness with respect to 9 controls. These alterations correlated with severe impairment in the amount and/or the architectural arrangement of bone material (volume, wall/lumen ratio, sectional inertia) and also with reduction of Ca content and modulus of elasticity of bone tissue. No changes were observed, however, in bone elastic stress. The impairment in stiffness derived from reductions in both bone mass and modulus of elasticity led to an increment in energy absorption by bone and bone tissue which in turn induced a high incidence of comminuted fractures. The data provide a biomechanical basis for the interpretation of clinical features of nutritional osteopenia in long bones.

Animals↗

PubMed1988

Exocrine secretion of immunoreactive erythropoietin from the rat submaxillary gland.

The physiological role of immunoreactive erythropoietin (iEp) in rodent submaxillary glands (SMG) is largely unknown. We studied in vivo the effects of cholinergic and adrenergic agents in male rats with respect to exocrine secretion of iEp into saliva. Intravenous administration of metacholine (20 micrograms/kg), norepinephrine (30 micrograms/kg), and isoproterenol (30 micrograms/kg) resulted in equal volumes of saliva over 1 h. None of the drugs altered circulating plasma levels and kidney concentrations of iEp. Salivary secretions induced by either norepinephrine or isoproterenol, both adrenergic agonists, contained high levels of iEp and a significant depletion of gland content was observed, suggesting that SMG exocrine iEp secretion is mediated by adrenergic receptors. In contrast, metacholine-stimulated glands retained their full iEp content and iEp was undetectable in saliva, indicating that cholinergic activity is not associated with exocrine secretion of iEp from SMGs.

Animals↗

PubMed1987

Mandibular growth retardation in growing rats chronically exposed to hypobaria.

Weanling male Wistar rats aged 21 days were divided into three groups: initial control, normobaric, and hypobaric (C, N, and H, respectively). C rats were killed three days after being weaned. H rats were placed into an altitude chamber and maintained at 456 mb (6100 m) for 14 days. N rats were maintained at sea-level conditions. Body weight, body and tail lengths, and food intake were recorded every day. Animals were killed at the end of the experimental period, and four linear dimensions of the dried mandible were measured. The amount of food eaten by the H rats during the entire exposure period was 54.6% of that consumed by N ones. Body weight gain in H rats was 32.7% of that seen in N rats. Body length was 49.0% and tail length was 56.6% of normal. All mandibular dimensions were significantly reduced in H rats when compared with N rats and were, in general, in close relation with the reduction observed in skeletal growth. Only one dimension was reduced out of proportion, which indicates some deformation of the mandible. The average daily caloric intake related to metabolic body weight (body weight 0.75) of H rats was 60% of the N value. Efficiency of protein utilization for growth was not significantly different between both groups of rats. These results indicate that chronic exposure to hypobaria induces overall skeletal and mandibular growth retardation, which appears to be the result of a diminution in food intake because of decreased appetite.

Altitude↗

PubMed1987

Impeded eruption rate of the rat maxillary incisor during exposure to different simulated altitudes.

Female rats weighing about 200 g each were separated into normoxic and hypoxic groups. The former were maintained at sea-level conditions. The hypoxic groups were placed in an altitude chamber and maintained at the equivalent of 1850 m, 4100 m, or 7100 m over a period of two weeks. Hematocrit, body weight, body length, and impeded eruption rate were recorded once a week. Food intake was recorded every day. Exposure to 1850 m did not significantly alter hematocrit, body weight and body length gains, food intake, and impeded eruption rate. Nevertheless, exposure to 4100 m and 7100 m decreased body weight and body length gains, food intake, and impeded eruption rate, and increased hematocrit value. These parameters varied as a function of altitude. In spite of the lack of conclusive evidence, this work affords further insight into the particular significance of polycythemia on the eruption rate.

Altitude↗

PubMed1987

Effect of prenatal ethanol exposure on the growth of rat mandible skeletal units.

To study the effect of prenatal ethanol exposure on the growth of the skeletal units of the rat mandible, female Sprague-Dawley rats weighing 220-240 g were assigned to 1 of 3 different groups. One of the groups received ethanol in the drinking water (up to 10% v/v) for at least 15 days prior to mating, then 20% (v/v) throughout gestation. A balanced diet was supplied ad libitum. A second group was pair-fed with the first group. In addition, an amount of corn starch calorically equivalent to the amount of ethanol consumed by that group was offered. The remaining group formed the normal control and received food and water ad libitum. All groups were offered food and water ad libitum after delivery. Total caloric intakes in the first 2 groups. were 67.8% of that of the normal control group. The average off-spring weight at birth for rats given ethanol was 17% lower than that of normal control rats. There was no significant difference between the average weights of the offspring of pair-fed and normal control rats. During the ensuing 3 weeks, the weight of the offspring of alcoholic rats showed no indication of catching-up. All skeletal units of the mandible of the offspring of ethanol-treated females differed significantly from those of the control group. These differences varied between 2% and 16%. The skeletal units of mandibles of the pair-fed group did not differ significantly from ad libitum controls. The mandibular width was similar in all 3 experimental groups.

Animals↗

PubMed1986

Relationship between severity of renal damage and erythropoietin production in uranyl nitrate-induced acute renal failure.

Adult female Wistar rats were injected with 1 mg/kg body weight of uranyl nitrate (UN). Evaluation of renal function, histopathology studies, and determination of plasma erythropoietin (Ep) titers after exposure to 456 mb for 16 h were performed at 1, 2, 7, 10, 15, and 21 days after drug injection. Plasma urea and creatinine concentrations markedly increased during the first seven days after injection, reaching maximal values on day 7 and decreasing thereafter. Significant increases in urine volume and significant depressions in urine osmolality also were observed; both alterations were most marked on day 7 after injection. A coagulative necrosis of the epithelium of proximal convoluted tubules, desquamation of the necrotic cells, and dilation or collapse of the tubular lumen were observed; the lesions were more marked on day 7. Plasma Ep levels in UN-treated rats exposed to hypobaria were markedly lower than in noninjected controls similarly exposed. Measurements were performed one, two, and seven days after UN injection, with maximal depression observed on day 7. These observations indicate that there is a correlation between the extent of both tubule damage and degree of renal dysfunction and plasma Ep production during exposure to hypoxia in UN-treated rats. This suggests that the renal Ep component is derived primarily from tubular cells.

Acute Kidney Injury↗

PubMed1986

Hypoxia-induced renal and extrarenal erythropoietin production in posthypoxic or hypertransfused polycythemic rats.

The erythropoietic response, measured as 59Fe uptake by RBC, and the erythropoietin content of kidney tissue after exposure to hypobaric hypoxia were determined in both posthypoxic (PH) and hypertransfused (HT) rats. Plasma Ep titers were also measured in both PH and HT nephrectomized rats treated similarly. PH and HT rats with similar degrees of polycythemia greatly differed in their responses to hypoxia, with radioiron uptake by RBC about six times higher in the former than in the latter. Kidney Ep titers were significantly enhanced after exposure to hypoxia in either normal or polycythemic rats. However, kidney Ep titers in PH rats were significantly higher than the values found in normal or HT rats. Plasma Ep titers in both PH and HT nephrectomized rats exposed to hypoxia were similar and significantly lower than the plasma values of normal or nephrectomized, nonpolycythemic rats treated similarly. These results suggest that exposure to hypoxia induces sensitization of the renal, but not extrarenal, mechanism involved in Ep production.

Animals↗

PubMed1985

Effect of acute exposure to reduced atmospheric pressures on body weight, food intake and body composition of growing rats.

Growing male rats were exposed to simulated altitudes of 1850, 2900, 4100, 5450 or 7100 m in a hypobaric chamber to determine the effects of altitude on body weight gain and food intake as function of time of exposure. Female rats were exposed to a simulated altitude of 7100 m for 24 h to determine the effect of altitude on body composition. The results obtained indicate that in growing rats exposed to acute simulated altitude the initial body weight loss and the depressed growth rate, on one hand, and the reduced food intake, on the other hand, are related to the degree of the altitude; the parameters are not affected at altitudes below 1 850 m; the initial weight loss is not solely due to reduction in food intake, the additional loss being attributed to the added stress of hypoxia; the body weight loss occurs without marked alterations in body composition, although a tendency to dehydration exists; and the body compositional changes are the reflection of the altitude-induced hypophagia.

Altitude↗

PubMed1985

Comparison of erythropoietic response to erythropoietin-secreting stimuli in mice following polycythemia induced by transfusion or hypoxia.

The erythropoietic response, measured as RBC-59Fe uptake, in response to either 24-h exposure to hypoxia or administration of dexamethasone, isoproterenol, testosterone, or erythropoietin, was determined in both posthypoxic (PH) and hypertransfused (HT) polycythemic mice. Highly significant differences between PH and HT mice exposed to hypoxia or injected with dexamethasone, isoproterenol, or testosterone were observed, isotope incorporation being always higher in PH than in HT mice. On the other hand, the response to erythropoietin did not show a significant difference between PH and HT mice. These results suggest that PH mice have been preconditioned by exposure to hypoxia in a way that makes them more sensitive to at least some kinds of erythropoietic stimuli. Since these stimuli have been shown by others to increase erythropoietin production, the results support our hypothesis that hypoxia induces sensitization of the erythropoietin-producing organ(s).

Animals↗

PubMed1984

Suppressive effect of acetylsalicylic acid on erythropoietin-responsive cells in mice.

The time-response curve for RBC-59Fe uptake following i.p. injections of 3 doses of 5 mg of acetylsalicylic acid (ASA) at 4 hour interval into normal, nonpolycythemic mice, shows a maximal depression (35% of normal) at 3 days after ASA with return to almost normal values by 7 days. The effect is dose-related, showing a plateau with doses of ASA above 5 mg/4 hr. The shape of the time-response curve indicates that the more mature cells in the erythron are not affected by ASA and that the major effect of the drug must be on earlier erythroid cells. Administration of ASA prior to administration of erythropoietin (Epo) into post-hypoxic polycythemic mice depresses the incorporation of 59Fe into erythrocytes. The depression of radioiron uptake is similar when ASA is given prior to or simultaneously with Epo. When ASA is given 24 hr after injection of Epo, suppression is less marked. These results suggest a suppressive effect of the drug on the erythropoietin-responsive cells (ERC).

Animals↗