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Biomedical subjects

C Di Giulio

Publications and source records attributed to C Di Giulio.

At least 37 records · Page 2Linked to original sources
PubMed1998

The prognostic value of soluble interleukin-6 receptor in patients with multiple myeloma.

BACKGROUND: The effect of interleukin-6 (IL-6), the major growth factor for myeloma cells, may be enhanced by soluble IL-6 receptor (sIL-6R). Therefore, the current study investigated the clinical significance of serum sIL-6R in patients with multiple myeloma (MM). METHODS: Serum levels of sIL-6R were determined by enzyme-linked immunoassay in 55 normal controls, 81 individuals with monoclonal gammopathy of undetermined significance (MGUS), and 164 patients with MM in various phases of the disease. RESULTS: sIL-6R concentrations were higher in MM patients (162.0 +/- 134.6 ng/mL) than in individuals with MGUS (58.9 +/- 36.7 ng/mL) or in controls (45.6 +/- 22.3 ng/mL) (P = 0.0000). sIL-6R was not found to have a significant linear correlation with any other parameter, including IL-6, beta2-microglobulin (beta2-m), and neopterin, either in newly diagnosed cases or during the course of the disease. In addition, there were no statistically significant differences in sIL-6R concentrations between the clinical stages at the time of diagnosis. In univariate logistic regression analysis sIL-6R was a significant but weak prognostic indicator (P = 0.000000). Kaplan-Meier analysis showed that elevated levels of sIL-6R were associated with shorter survival (P = 0.00282). Patients also were stratified according to their serum beta2-m and sIL-6R levels. Patients with low levels of both parameters had a clear survival benefit over the other groups (P = 0.000000). CONCLUSIONS: The correlation between sIL-6R levels and survival is significant but weak, making it unlikely to be of much value in predicting the outcome of patients with MM alone. The results of the current study support the role of sIL-6R levels in improving the prognostic value of beta2-m and in discriminating patients with MM from individuals with MGUS.

Adult↗
PubMed1998

Hypoxic and hyperoxic effect on blood phosphodiesterase activity in young and old rats.

In the present work we describe phosphodiesterase (PDEs) activity in the blood of young and old rats kept under hypoxic or hyperoxic normobaric conditions in order to correlate the age-change response with PDE levels and oxygen supply. PDE is important in the process of energy supply and as a modulator and mediator of several cellular functions. Three groups of Wistar rats were kept in room air, 10-12% oxygen for 12 days and 98-100% oxygen for 60 hrs respectively. Each group was composed of young rats (2 months of age) and old rats (25 months of age). After the exposure the rats were anaesthetized and blood samples were collected using an intracardiac catheter. The results show: a) in the control group, no significant difference between the PDE activities of old and young rats; b) a significant increase in PDE occurred after hypoxic and hyperoxic treatment in both young and aged rats; c) the increase in PDE activity was more evident in the young rather than the old rats; and d) the aged rats are less responsive to oxygen variation. The results demonstrate that young and aged rats respond to variations in the oxygen supply. Hypoxia and hyperoxia show different age-related intensity level response. We conclude that the alteration in PDE expression occurring in the blood as a consequence of hypoxic or hyperoxic treatment is probably a necessary protective response for the body against alteration from oxidative metabolism and to maintain the body in homeostatic ranges for energy requirements.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Effect of chronic hyperoxia on young and old rat carotid body ultrastructure.

Morphologic, physiological, and biochemical changes occur in the carotid body (CB) during postnatal development in relation to physiological requirements. Chronic normobaric hyperoxia attenuates the carotid chemosensory response to hypoxia. During aging there is less of a CB response to hypoxia, which results in a reduced ventilatory adaptation and chemosensory discharge. To test if the oxygen-sensitive mechanism is affected by chronic hyperoxia in an age-dependent fashion, we have studied structural and ultrastructural aspects of young and old rat CBs. Four groups of six male Wistar rats were used. One group of two-month-old rats and another of 25-month-old rats were kept at room air. The other two groups, age matched, were exposed to 98-100% O2, for 60-65 h, in a large Plexiglas chamber. The rats were anesthetized, CBs were fixed in situ with glutaraldehyde (2.5% in phosphate buffer. pH 7.4, 320 mOsm), and were prepared for electron microscopy. Young hyperoxic rats showed focal necrosis in type I cells, along with an increase of endoplasmic reticulum, Golgi apparatus, and of mitochondria volume, with loss of cristae. These changes were less pronounced in the older rat CBs compared with the young rats. In conclusion, hyperoxia seems to affect the oxygen-sensitive mechanism in the carotid body cells, and the reduced effects shown in the old rat CBs suggest an age-related decreased sensitivity to oxygen.

Aging↗
PubMed1998

Does chronic hypoxia increase rat carotid body nitric oxide?

The carotid body plays an important role in ventilatory adaptation during chronic hypoxia. Nitric oxide (NO) may act as a regulator in neurotransmission, influencing the carotid body chemosensory discharge. The aim of the study was to understand if NO could contribute to the adaptation process during chronic hypoxia. The rats were kept in chronic hypoxia (10-11% inspired oxygen) for 12 days, while the controls were kept in room air (21% O2). The distribution for diaphorase activity and immunohistochemistry for nitric oxide synthase (NOS) showed that chronic hypoxia induces an increase in NOS activity in the carotid body. It was concluded that NO release increased during chronic hypoxia and causes an inhibitory effect on carotid chemosensory discharge of the rat carotid body.

Adaptation, Physiological↗
PubMed1997

Aging and detoxifying enzymes responses to hypoxic or hyperoxic treatment.

We studied the levels of antioxidant and detoxifying enzymes in the livers and lungs of young and old rats kept under hypoxic or hyperoxic conditions as models of oxidative stress. In particular, we investigated the levels of enzymes directly involved in active oxygen species scavenging (superoxide dismutase, catalase and glutathione peroxidase-selenium dependent) and enzymes challenged with detoxification processes (glutathione transferase, glyoxalase I and glutathione reductase) in order to obtain a wide comparative view of the defence strategies used with respect to the age of the animals. The results show that the responses of some protective enzymes in young rats are opposite to those of old ones. Some of the changes found appear mainly due to age, while others appear to be due only to the oxygen tensions and are independent of the aging process. The glutathione contents of the liver and lung from young and old rats under hypoxic and hyperoxic conditions were measured.

Aging↗
PubMed1997

Response to recombinant human erythropoietin in patients with myelodysplastic syndromes.

Recombinant human erythropoietin (rhEPO) at pharmacological doses was used to improve anemia and reduce the transfusional requirements of 43 patients with myelodysplastic syndrome (MDS). rhEPO was given by s.c. injection three times per week for 12 weeks. The EPO dose was started at 150 IU/kg and was increased to 300 IU/kg if after 6 weeks there was no or suboptimal erythroid response. Responses were defined as being a complete response (CR), partial response (PR), or no response (NR). A CR was considered a rise in untransfused hemoglobin concentrations of at least 2 g/dl or a 100% decrease in RBC transfusion requirements over the treatment period. A PR was defined as an increase in untransfused hemoglobin values of 1-2 g/dl or a decrease in RBC transfusion requirements equal to or greater than 50%. NR was defined as responses less than a PR. Patients who responded to therapy were continued on rhEPO at the same dose for 6 additional months. An objective response (CR and PR) was observed in 7 of 42 (16.7%) assessable cases after 6 weeks of treatment at the dose of 150 IU/kg. Dose escalation (300 IU/kg) in nonresponders resulted in another six patients attaining a rise in hemoglobin concentrations. The final response rate was 13 of 41 (31.7%); 4 patients became transfusion independent. Therapy was tolerated well, with no relevant side effects. MDS progression was seen in one case. An elevated bone marrow erythroid infiltration (erythroid index) and detectable pretreatment circulating erythroid progenitors (burst-forming units-erythroid) were the best predictors of hemoglobin response when we controlled for other variables. These data suggest that rhEPO has a role in the treatment of certain patients with MDS, particularly in those with a high erythroid index and detectable circulating erythroid burst-forming units.

Adult↗
PubMed1996

Alteration of glutathione transferase subunits composition in the liver of young and aged rats submitted to hypoxic and hyperoxic conditions.

In the present work, we have studied glutathione transferase (GST) activity and GST subunits distribution in the liver of young and aged rats kept under hypoxic or hyperoxic normobaric conditions as model of oxidative stress. A significant decrease of GST activity was detected in young hypoxic rat liver, whereas a significant increase occurred in aged hypoxic liver. No significant alteration of activity was obtained in both young and aged rat livers subjected to hyperoxic treatment. Substrate specificity measurements, SDS/PAGE analysis and reverse-phase HPLC, of GSH-affinity purified fractions were used to study the changes in the GST subunits pattern occurring in the liver of rat as a consequence of hypoxic and hyperoxic treatment. The results demonstrate that young and aged rat liver has a different constitutive GST subunit pattern which are markedly and differentially altered in hypoxia or hyperoxia. The hyperoxic treatment caused an increase of GST subunit 3 in aged, but not in young liver. In aged liver, both the hypoxic and hyperoxic treatment produced a decrease of GST subunit 4. After hypoxic treatment GST subunit 3 significantly increased in both young and aged liver. GST subunit 1a increased in both young and adult liver after hyperoxia. Following hypoxia a decrease of subunit 1a was seen in both young and aged liver. After hypoxic treatment, subunit 6 doubled in young, but not in aged, livers. It was concluded that the alterations in GST subunit expression occurring in the liver as a consequence of hypoxic or hyperoxic treatment respond to the necessity of a better protection of liver against the products of oxidative metabolism.

Aging↗
PubMed1994

Effect of acute and chronic cobalt administration on carotid body chemoreceptors responses.

Chronic cobalt exposure leads to release and production of erythropoietin and consequently to polycythemia. Accordingly, cellular elements sensitive to oxygen in the carotid body, would manifest responses during acute and chronic cobalt administration. The carotid body, detects gas changes (PO2, PCO2/pH) in the arterial blood and regulates ventilation and circulation by the afferent nerve discharge. We hypothesized that cobalt interacts with an oxygen sensitive mechanism in the carotid chemoreception and in erythropoietin producing cells. Twelve cats were anesthetized, paralysed and artificially ventilated; few fiber preparation of carotid sinus nerve were recorded during close intraarterial injection of cobalt. In another protocol, 12 rats received an intraperitoneal dose of CoCl2 (10 mg/kg) daily for 6 weeks. At the end, the carotid body was fixed in situ by superfusion. Ultrastructural and morphometric studies were made. Acute administration (0.08-2.3 mumol) promptly stimulated the chemoreceptor afferents. Type I cells increased significantly along with erythropoiesis in the chronic cobalt treated rats. The stimulatory effects of cobalt on the carotid body chemoreceptor showed that sensitive mechanisms in the kidney and in the carotid body are similar, and cobalt interacts with the physiological responses of oxygen.

Animals↗
PubMed1994

Potentiometric determination of carbonic anhydrase activity in rabbit carotid bodies: comparison among normoxic, hyperoxic and hypoxic animals.

The catalytic activity of carbonic anhydrase (CA) contained in the glomus cells of mammalian carotid bodies has been determined in vitro by a potentiometric method. Experiments performed on whole rabbit carotid bodies have shown a very low variability, in terms of the overall CA activity, among organs belonging to different animals maintained in normoxic conditions. Repeated assays performed on each carotid body have shown a marked decrease of the overall CA activity after the first assay, thus suggesting the presence of at least two different forms of enzyme. Experiments performed on carotid bodies belonging to rabbits maintained in normal, hyperoxic and hypoxic conditions have shown that the overall CA activity follows the sequence: hypoxic > normoxic > hyperoxic, matching with the corresponding physiological activity of the carotid body.

Animals↗
PubMed1992

Carotid chemoreceptor response to natural stimuli in the newborn kitten.

The activities of carotid chemoreceptors at three levels of inspired PO2 (55, 145 and 690 Torr) and at two levels of inspired PCO2 (35 and 70 Torr in O2) were studied in 28 anesthetized, mechanically ventilated kittens aged 0-17 days. A biphasic response to hypoxia was found in 46% of them: the chemosensory activity increased to a peak within 30 sec after the initial response to hypoxia and thereafter declined slowly to a stable value. The steady-state single-fiber chemosensory activity at an inspired PO2 of 55 Torr was significantly lower in kittens less than 10 days old (mean +/- SE: 5.8 +/- 0.6 impulses.sec-1) than in the older ones (8.8 +/- 1.3 impulses.sec-1, P less than 0.03). The response curves to arterial PO2 were hyperbolic in both groups but the curve for the younger kittens was displaced to the left of the curve for the older ones. The response to hypercapnia was a progressive increase in chemosensory activity with little evidence of rapid or slow adaptation. The response to hypercapnia was significantly stronger in the older kittens than in the young ones. It is concluded that, in the kitten, the carotid chemoreceptor response to hypoxia may be biphasic. The responses to hypoxia and hypercapnia are already developed but are weak at birth and continue to develop further during the first weeks of postnatal life.

Animals↗
PubMed1991

Chronic cobalt causes hypertrophy of glomus cells in the rat carotid body.

We tested the hypothesis that chronic cobalt administration would induce carotid body cellular response along with polycythemia as found in chronic hypoxia if common oxygen-sensitive mechanisms were involved in the two instances. Morphometric studies were performed on carotid bodies in male rats that were chronically treated with cobalt chloride (0.17 mumol/kg, ip, daily for 6 wk) and in control rats that received blank saline injections. The rats were anesthetized, blood samples were collected for hematocrit, and the carotid bodies were surgically exposed and were perfused and superfused with the buffered fixative (3% glutaraldehyde plus 1% paraformaldehyde, pH 7.40, 330-340 mosM). The carotid bodies were processed, and ultrathin sections were cut for electron microscopy and morphometry of type I (glomus) and type II cells. Hematocrit increased from 44% in the control to 74% in the cobalt-treated rats, and the mean volume of type I cells increased from 424 to 1,061 microns 3. Type II cells did not show any significant change in size. The results suggest that cobalt stimulated oxygen-sensitive mechanism in the glomus cells of the carotid body and that the glomus cell is a site of oxygen chemosensing.

Animals↗
PubMed1990

Cobalt stimulates carotid body chemoreceptors.

Because cobalt administration is known to elicit erythropoietin response, it is a reasonable hypothesis that cobalt would also stimulate the O2-sensing process in the peripheral chemoreceptors. We tested this hypothesis by measuring the effects of cobalt chloride on carotid chemosensory fibers in pentobarbital-anesthetized cats that were paralyzed and artificially ventilated. Responses of carotid chemoreceptor afferents to graded doses of cobalt given by intra-arterial injections (0.08-2.10 mumols) were measured at constant blood gases. Responses of the same chemoreceptor afferents to hypoxia, before and after a saturation dose of cobalt, were measured. In two experiments carotid body tissue PO2 was also simultaneously measured. The chemosensory fibers showed prolonged excitation after a brief period of inhibition subsequent to cobalt administration. The stimulatory effect showed a dose-dependent saturation response. Cobalt augmented rather than blocked carotid chemoreceptor response to hypoxia. The effect of cobalt was not mediated by tissue PO2. These results are consistent with the hypothesis that cobalt stimulates the O2-sensing mechanism, although a direct effect of cobalt on the excitability of the chemosensory terminal remains a possibility.

Animals↗
PubMed1990

Soluble interleukin-2 receptor in vitro production by mononuclear cells from Hodgkin patients.

Lymphocytes of patients with Hodgkin's disease have a deficient production of Interleukin-2. Recently, a soluble form of the receptor for IL-2 has been demonstrated in human sera and in vitro-stimulated culture supernatants from human T lymphocytes. In the present paper we report the production of soluble IL-2R from peripheral blood mononuclear cells in H.D. The unstimulated MNC of patients released more sIL-2R than controls. No difference was observed between PHA-stimulated MNC of patients and controls. These preliminary findings suggest that soluble IL-2R may be provide a new tool for the study of immunological dysregulation in H.D.

Adolescent↗
PubMed1989

Sympathetic peripheral chemoreflex is independent of expiratory output neurons in the cat.

Previously we reported that activities of certain chemoreflex sensitive cervical preganglionic sympathetic nerves (PSN) were augmented by carotid chemoreceptor stimulation independently of phrenic nerve (PN) activity in the cat. To test the hypothesis that the PSN carotid chemoreflex could have been mediated by the expiratory neuron activity, we studied the relationship between PSN, internal intercostal expiratory nerve (IICEN) and PN activities in vagotomized, anesthetized, paralysed and artificially ventilated cats. We made the following observations. (1) Hypoxia often inhibited IICEN activity while the PN and PSN activities were stimulated. (2) during normoxia, cyanide strongly stimulated PN and PSN discharges but only moderately IICEN discharges. (3) Hyperventilation hypocapnia suppressed or eliminated PSN and PN rhythms and activities, but made some IICEN fibers fire continuously. (4) During hypocapnic apnea, cyanide stimulated PSN activity before PN and IICEN activities, although some PSN fibers were stimulated simultaneously with PN fibers. Accordingly we conclude that IICEN activity does not significantly influence chemoreflex stimulation of PSN activity and that a direct chemoreflex stimulation of IICEN is minimal in the cat. Thus, the chemoreflex PSN response is in part independent of respiratory chemoreflex pathways.

Action Potentials↗