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Biomedical subjects

R Favier

Publications and source records attributed to R Favier.

At least 19 recordsLinked to original sources
PubMed1998

Polyalkylcyanoacrylate nanoparticles as carriers for granulocyte-colony stimulating factor (G-CSF).

The human recombinant granulocyte colony-stimulating factor (rhG-CSF) is largely used in the treatment of neutropenia occurring during chemotherapy. After injection, this glycoprotein distributes through the whole body. Thus, to obtain high and durable bone marrow concentrations, targeting with polyalkylcyanoacrylate nanoparticles was considered. Two methods of preparation were investigated: anionic polymerization and precipitation of the preformed polymer. By anionic polymerization, it was possible to associate more than 66% of rhG-CSF with nanoparticles (polyisobutyl- or polyisohexylcyanoacrylate nanoparticles) when the glycoprotein was added at the end of the polymerization process. It has been shown that the rhG-CSF was mainly adsorbed on the surface of the nanoparticles and most of the colony stimulating activity was conserved. Using precipitation of performed polyisohexylcyanoacrylate, 90% of rhG-CSF was associated with nanoparticles, the protein being mainly adsorbed onto the nanoparticle surface. In this case, a decrease of the colony stimulating activity was however observed. Whatever the method used, the in vitro release of rhG-CSF from the polyisohexylcyanoacrylate nanoparticles, was progressive during 8 h in seric conditions. Nevertheless, using mice as an animal model, it has been shown that the short-term effects of intravenously injected rhG-CSF were not increased by its association with polyisohexylcyanoacrylate nanoparticles.

Animals↗
PubMed1998

A case of intramedullary haematoma associated with congenital alpha2-plasmin inhibitor deficiency.

The association of intramedullary haematoma of the left femoral diaphysis and congenital alpha2-plasmin inhibitor deficiency in a 6-year-old boy is reported. Congenital deficiency of this fibrinolytic system component is very rare and can result in severe bleeding. Clinically, an intramedullary haematoma causes pain but no swelling, and there is no history of trauma. X-rays show a hyperlucent lesion without sclerotic edges in the medulla of the diaphysis of a long bone with thinning of the cortex. MRI is diagnostic with the haematoma generating a specific hyperintense signal on T1-weighted and T2-weighted spin-echo images.

Bone Marrow Diseases↗
PubMed1998

Exercise training in chronic hypoxia has no effect on ventilatory muscle function in humans.

At the highest altitude, aerobic work is limited by environmental oxygen availability. We therefore reasoned that the hyperpnea associated with endurance training at altitude should provide a strong stimulus for adaptation of the ventilatory muscles. We measured peak inspiratory muscle pressure-flow characteristics (inspiring through graded resistors) and maximum sustainable ventilation capacity in ten permanent residents of La Paz, Bolivia (3600 m) prior to and immediately following 6 weeks of incremental endurance training. Additionally, eight local residents did no training and functioned as controls for the capacity test. While V(O2)max measured in hypoxia increased by 19% (Favier et al., 1995b. J. Appl Physiol. 78, 2286-2293.), none of the tested ventilatory variables showed significant changes. The values for the group mean slopes of maximum inspiratory pressure-flow pairs (- 10.5 vs. - 9.8 cm H2O x sec x L(-1), P=0.301; before versus after training, respectively), maximum inspiratory pressure (112.1+/-8.9 vs. 106.9+/-8.6 cmH2O, P=0.163), peak inspiratory flow (9.8+/-0.41 vs. 10.2+/-0.55 L x sec(-1) P=0.172) and the maximum volitional volume in 12 sec (43.9+/-2.4 vs. 45.6+/-2.4 L in 12 sec, P=0.133) were unchanged with exercise training. Likewise, maximal sustainable minute volume was not different between post-training and control subjects (177.4+/-7.9 vs. 165.4+/-8.4 L x min(-1), P=0.141). These data support the concept that endurance training fails to elicit functional adaptations in ventilatory muscles in humans, even when exercise is done in hypoxia.

Acclimatization↗
PubMed1998

Simultaneous administration of antithrombin III and protein C concentrates for the treatment of a devastating coagulopathy in a child.

Severe disseminated intravascular coagulation (DIC) is a rare event in childhood. We report here a young body with a devastating DIC unresponsive to heparin, fresh frozen plasma and platelet support. This prompted the use of antithrombin III and protein C concentrates and the effects of this combination were temporarily spectacular. We suggest that the simultaneous administration of two inhibitors of blood coagulation could be of interest and should be evaluated in appropriate trials for the treatment of a devastating coagulopathy.

Antithrombin III↗
PubMed1997

Body fluid homeostasis and cardiovascular adjustments during submaximal exercise: influence of chewing coca leaves.

The present study was undertaken to determine the haematological and cardiovascular status, at rest and during prolonged (1h) submaximal exercise (approximately 70% of peak oxygen uptake) in a group (n = 12) of chronic coca users after chewing approximately 50 g of coca leaves. The results were compared to those obtained in a group (n = 12) of nonchewers. At rest, coca chewing was accompanied by a significant increase in heart rate [from 60 (SEM 4) TO 76 (SEM 3) beats.min-1], in haematocrit [from 53.2 (SEM 1.2) to 55.6 (SEM 1.1)%] in haemoglobin concentration, and plasma noradrenaline concentration [from 2.8 (SEM 0.4) to 5.0 (SEM 0.5) mumol.l-1]. It was calculated that coca chewing for 1 h resulted in a significant decrease in blood [-4.3 (SEM 2.2)%] and plasma [-8.7 (SEM 1.2)%] volume. During submaximal exercise, coca chewers displayed a significantly higher heart rate and mean arterial blood pressure. The exercise-induced haemoconcentration was blunted in coca chewers compared to nonchewers. It was concluded that the coca-induced fluid shift observed at rest in these coca chewers was not cumulative with that of exercise, and that the hypovolaemia induced by coca chewing at rest compromised circulatory adjustments during exercise.

Adolescent↗
PubMed1997

Influence of gender and endogenous sex steroids on catecholaminergic structures involved in physiological adaptation to hypoxia.

Mechanisms underlying sex-related differences in adaptation to high altitude were investigated by assessing the turnover of dopamine and noradrenaline in structures of the chemoafferent pathway, i.e. carotid body and brainstem noradrenergic cell groups (A1, A5, A6, A2 to which chemosensory fibres project). The influence of gender was assessed in male and female rats reared at an altitude of 3600 m, whereas the influence of endogenous sex hormones was evaluated by castration. Haematocrit, red blood cell count and plasma erythropoietin levels were lower in females than in males (-5%, -15%, -53%, respectively). Dopamine and noradrenaline turnover were higher in female structures (carotid body: +51%; A2: +140%; A1: +54%; A5: +27%). Dopamine and noradrenaline turnover in carotid body and brainstem cell groups were differently affected by castration, i. e. enhanced by orchidectomy (carotid body: +134%; A2: +120%; A1: +69%; A5: +67%) but inhibited by ovariectomy (carotid body: -33%; A2: -92%). Orchidectomy elicited a reduction in haematocrit (-10%), haemoglobin concentration (-8%) and red blood cell count (-24%), whereas haematological status remained unaltered after ovariectomy. Therefore, both gender and endogenous sex steroids may control catecholamine activity differently in structures involved in the chemoafferent pathway, thus providing a neurochemical basis for sex-related differences in adaptation to hypoxia.

Adaptation, Physiological↗
PubMed1997

Differential effects of ventilatory stimulation by sex hormones and almitrine on hypoxic erythrocytosis.

In the absence of pulmonary disease, hypoventilation is considered to be the primary cause of Chronic Mountain Sickness, and there is some reason to believe that chronic administration of respiratory analeptics could be useful for treatment of this disease. The present study was intended to define comparatively the influence of two potent ventilatory stimulants, namely a combination of progesterone and estrogen and the pharmacological agent almitrine, on catecholaminergic structures implicated in the chemoreflex pathway and on hypoxia-induced polycythemia. Three groups of young male rats born and living at high altitude (3 600 m) were examined: untreated animals (n = 25), rats given ovarian steroids (progesterone plus 17beta-estradiol, n = 25) or almitrine (n = 25) for 6 weeks until sacrifice. Ovarian steroids or almitrine had pronounced neurochemical effects on the afferent chemoreflex circuitry. Both treatments inhibited norepinephrine (NE) and dopamine (DA) turnover in the carotid body, but central processing of chemosensory inputs differed between the two respiratory drugs. Ovarian steroids inhibited noradrenergic activity in the projection area of the chemosensory nerve fibers within the caudal portion (A2C) of the nucleus tractus solitarius (NTS). In contrast, almitrine stimulated neurochemical activity of other brainstem noradrenergic cell groups involved in cardiorespiratory control, i.e. , the rostral portion (A2R) of the NTS, the nucleus reticularis lateralis (A1), the nucleus olivaris superior (A5) and the locus ceruleus (A6). Although both treatments increased chemoreflex drive and ventilation, only sex hormones decreased erythropoietin (EPO) levels and the degree of polycythemia. These results suggest that stimulation of ventilation through activation of peripheral arterial chemoreceptors activation alone is not sufficient for reducing EPO levels and polycythemia. The better efficiency of female sex hormone treatment as compared to almitrine could be related either to the central effects of progesterone and estrogen and/or to the impact of these hormones on erythropoiesis at the kidney/bone marrow level.

Almitrine↗
PubMed1997

Fluid regulatory hormone response to exercise after coca-induced body fluid shifts.

To determine the effect of coca chewing on heart rate (HR), mean arterial blood pressure (MAP), and plasma volume and their relationship with the hormones regulating cardiovascular and body fluid homeostasis, 16 male volunteers were examined at rest and during 1 h of cycle exercise at approximately 75% of their peak oxygen uptake in two trials separated by 1 mo. One trial was performed after the subjects chewed a sugar-free chewing gum (Coca- trial), whereas the other was done after the subjects chewed 15 g of coca leaves (Coca+), with the order of the Coca- and Coca+ trials being randomized. Blood samples were taken at rest, before (R1) and after 1-h chewing (R2), and during the 5th, 15th, 30th, and 60th min of exercise. They were analyzed for hematocrit, hemoglobin concentration, red blood cell count, plasma proteins, and for the fluid regulatory hormones, including plasma catecholamines [norepinephrine (NE) and epinephrine], renin, arginine vasopressin, and the atrial natriuretic peptide (ANP). During the control trial (Coca-), from R1 to R2, there was no significant change in hematologic, hormonal, and cardiovascular status except for a small increase in plasma NE. In contrast, it can be calculated that coca chewing at rest induced a significant hemoconcentration (-3.8 +/- 1. 3% in blood and -7.0 +/- 0.7% in plasma volume), increased NE and MAP, and reduced plasma ANP. Chewing coca before exercise reduced the body fluid shifts but enhanced HR response during exercise. These effects were not accompanied by changes in NE, epinephrine, renin, and arginine vasopressin plasma levels. In contrast, plasma ANP response to exercise was lower during the Coca+ trial, suggesting that central cardiac filling was reduced by coca use. It is likely that the reduction in body fluid volumes is a major contributing factor to the higher HR at any given time of exercise after coca chewing.

Adult↗
PubMed1996

Aerobic capacity and skeletal muscle properties of normoxic and hypoxic rats in response to training.

The aim of this study was to determine, in the rat, the effects of chronic exposure (7-9 weeks) to normobaric hypoxia (FIO2=0.13, equivalent to 3700 m altitude) on cardiac and skeletal muscle properties, on maximal oxygen uptake (VO2max), and endurance time to exhaustion (ETE). In addition, we evaluated the impact of endurance training (90 min of treadmill running per day, 5 days per week, for 9 weeks) on these parameters. The results were compared to normoxic rats fed ad libitum (NAL) and to normoxic pair-weight (NPW) animals in order to take into account the influence of hypoxia on growth rate. It was found that, in sedentary rats, hypoxia results in stunted growth, adrenal atrophy, a significant reduction of cross-sectional area of fast-twitch (type II) fibres, a reduced capillary-to-fibre ratio (C/F), and a reduced oxidative capacity (decreases in citrate synthase and 3-hydroxy-Acyl CoA dehydrogenase activities) of the plantaris muscle. These effects are mainly related to the anorexic effects of prolonged exposure to hypoxia. Nevertheless, hypoxic (H) rats displayed higher VO2max and ETE values when compared either to NAL or to NPW animals. Endurance training resulted, in all groups (H, NAL, NPW), in a significant change of the fibre type distribution of the plantaris which displayed an increased number of type IIA fibres and a decreased proportion of type IIB fibres. In addition, the C/F ratio and cross-sectional area of fast-twitch fibres were normalized by superimposition of training on hypoxia. Both VO2max and ETE were significantly higher in trained H rats than in NAL, but these improvements were mainly related to the reduced body weight induced by hypoxia. These data suggest that the greater aerobic capacity and tolerance for prolonged exercise induced by chronic exposure to hypoxia can be mainly accounted for by the anorexic effects of hypoxia, although other factors (e.g. increase in oxygen carrying capacity induced by hypoxia acclimatization) may play a significant role in some circumstances (e.g. in sedentary rats).

Acyl-CoA Dehydrogenase↗
PubMed1996

Hormonal and metabolic adjustments during exercise in hypoxia or normoxia in highland natives.

In sea-level natives, exposure to hypoxia for a few weeks is characterized by an increased dependence on blood glucose and a decreased reliance on lactate for energy metabolism during exercise. These metabolic adjustments have been attributed to behavioral changes in the sympathoadrenergic and pancreatic systems. The aim of this study was to test the hypothesis of a reduced sympathoadrenergic activation and subsequent metabolic changes when high-altitude natives are acutely exposed to normoxia. Young Andean natives performed incremental exercise to exhaustion during hypoxia (arterial PO2 55.1 +/- 1.1 Torr) or during acute normoxia (arterial PO2 78.7 +/- 1.7 Torr). As a whole, oxygen uptake was increased in normoxia compared with hypoxia during graded exercise. This finding is not related to a decrease in anaerobic metabolism but rather is interpreted as a consequence of a shift in substrate utilization during exercise (increased contribution of fat as assessed by a reduction in the respiratory exchange ratio). These metabolic changes are not accompanied by modifications of glucoregulatory hormones (catecholamines, insulin, and glucagon). In particular, the exercise-induced catecholamine secretion was similar in chronic hypoxia and acute normoxia. As a consequence, blood lactate accumulation during incremental exercise was similar in both conditions. It is concluded that high-altitude natives do not display any sign of a greater sympathoadrenergic activation during chronic hypoxia and that the exercise-induced hormonal changes remained unaffected by acute inhalation of a normoxic gas mixture.

Adult↗
PubMed1996

Effects of coca chewing on metabolic and hormonal changes during graded incremental exercise to maximum.

We examined the effects of 1 h of coca chewing on metabolic and hormonal responses during incremental exercise to exhaustion in traditional coca chewers (C; n = 8), and the results were compared with a group of nonchewers (n = 13). For 1 h, C chewed approximately 12 g of coca leaves that resulted in the apparition of cocaine in blood that reached 72 +/- 9 ng/ml. In resting conditions, even though sympathoadrenergic activity (as assessed by norepinephrine and epinephrine plasma levels) was similar in both groups, C displayed a higher level of plasma free fatty acids. Oxygen uptake measured at exhaustion and delta work efficiency during exercise were similar in both groups. During the incremental exercise, C displayed a significantly lower arterial oxygen saturation that cannot be explained by a reduced ventilatory response after coca chewing. In fact, even at maximal exercise, both ventilatory output and ventilatory equivalent were higher in C compared with nonchewers. It is concluded that the beneficial effects of coca chewing on exercise tolerance reported frequently by traditional coca users is not related to either an improved maximal exercise capacity or an increased work efficiency. However, during incremental exercise, coca chewing appeared to result in an increased free fatty acid availability that could be beneficial for prolonged submaximal exercise.

Adult↗
PubMed1996

Effects of coca chewing on hormonal and metabolic responses during prolonged submaximal exercise.

The effects of coca chewing on prolonged submaximal exercise responses were investigated in chronic coca chewers and compared with a group of nonchewers. At rest, coca chewing during a 1-h period was followed by a significant increase in blood glucose, free fatty acid, and norepinephrine concentrations and a significant reduction in insulin plasma level. During prolonged (1-h) submaximal (65-70% peak O2 uptake) exercise, chewers displayed a significantly greater adrenergic activation (as evidenced by a higher level of plasma epinephrine) and an increased use of fat (as evidenced by a lower respiratory exchange ratio). The gradual increase in oxygen uptake (O2 drift) commonly observed during prolonged exercise was blunted in coca chewers. This blunting in O2 drift is not related to coca-induced changes in ventilatory or lactate responses to exercise but could possible be related to an enhanced glucose utilization by chewers during the late phase of exercise. The present results provide experimental evidence of the physiological effects of coca chewing that could explain the better ability of coca users to sustain strenuous work for an extended period of time.

Adolescent↗
PubMed1996

Coca chewing for exercise: hormonal and metabolic responses of nonhabitual chewers.

To determine the effects of acute coca use on the hormonal and metabolic responses to exercise, 12 healthy nonhabitual coca users were submitted twice to steady-state exercise (approximately 75% maximal O2 uptake). On one occasion, they were asked to chew 15 g of coca leaves 1 h before exercise, whereas on the other occasion, exercise was performed after 1 h of chewing a sugar-free chewing gum. Plasma epinephrine, norepinephrine, insulin, glucagon, and metabolites (glucose, lactate, glycerol, and free fatty acids) were determined at rest before and after coca chewing and during the 5th, 15th, 30th, and 60th min of exercise. Simultaneously to these determinations, cardiorespiratory variables (heart rate, mean arterial blood pressure, oxygen uptake, and respiratory gas exchange ratio) were also measured. At rest, coca chewing had no effect on plasma hormonal and metabolic levels except for a significantly reduced insulin concentration. During exercise, the oxygen uptake, heart rate, and respiratory gas exchange ratio were significantly increased in the coca-chewing trial compared with the control (gum-chewing) test. The exercise-induced drop in plasma glucose and insulin was prevented by prior coca chewing. These results contrast with previous data obtained in chronic coca users who display during prolonged submaximal exercise an exaggerated plasma sympathetic response, an enhanced availability and utilization of fat (R. Favier, E. Caceres, H. Koubi, B. Sempore, M. Sauvain, and H. Spielvogel. J. Appl. Physiol. 80: 650-655, 1996). We conclude that, whereas coca chewing might affect glucose homeostasis during exercise, none of the physiological data provided by this study would suggest that acute coca chewing in nonhabitual users could enhance tolerance to exercise.

Adult↗
PubMed1996

Muscle tissue adaptations of high-altitude natives to training in chronic hypoxia or acute normoxia.

Twenty healthy high-altitude natives, residents of La Paz, Bolivia (3,600 m), participated in 6 wk of endurance exercise training on bicycle ergometers, 5 times/wk, 30 min/session, as previously described in normoxia-trained sea-level natives (H. Hoppeler, H. Howald, K. E. Conley, S. L. Lindstedt, H. Claassen, P. Vock, and E. R. Weibel. J. Appl. Physiol. 59: 320-327, 1985). A first group of 10 subjects was trained in chronic hypoxia (HT; barometric pressure = 500 mmHg; inspired O2 fraction = 0.209); a second group of 10 subjects was trained in acute normoxia (NT; barometric pressure = 500 mmHg; inspired O2 fraction = 0.314). The workloads were adjusted to approximately 70% of peak O2 consumption (VO2peak) measured either in hypoxia for the HT group or in normoxia for the NT group. VO2peak determination and biopsies of the vastus lateralis muscle were taken before and after the training program. VO2peak in the HT group was increased (14%) in a way similar to that in NT sea-level natives with the same protocol. Moreover, VO2peak in the NT group was not further increased by additional O2 delivery during the training session. HT or NT induced similar increases in muscle capillary-to-fiber ratio (26%) and capillary density (19%) as well as in the volume density of total mitochondria and citrate synthase activity (45%). It is concluded that high-altitude natives have a reduced capillarity and muscle tissue oxidative capacity; however, their training response is similar to that of sea-level residents, independent of whether training is carried out in hypobaric hypoxia or hypobaric normoxia.

Acclimatization↗
PubMed1996

Lactate and epinephrine during exercise in altitude natives.

We tested the hypothesis that the reported low blood lactate accumulation ([La]) during exercise in altitude-native humans is refractory to hypoxianormoxia transitions by investigating whether acute changes in inspired O2 fraction (FIo2) affect the [La] vs. power output (W) relationship or, alternatively, as reported for lowlanders, whether changes in [La] vs. W on changes in FIo2 are related to changes in blood epinephrine concentration ([Epi]). Altitude natives [n = 8, age 24 +/- 1 (SE) yr, body mass 62 +/- 3 kg, height 167 +/- 2 cm] in La Paz, Bolivia (3,600 m) performed incremental exercise with two legs and one leg in chronic hypoxia and acute normoxia (AN). Submaximal one- and two-leg O2 uptake (Vo2) vs. W relationships were not altered by FIo2. AN increased two-leg peak Vo2 by 10% and peak W by 7%. AN paradoxically decreased one-leg peak Vo2 by 7%, whereas peak W remained the same. The [La] vs. W relationships were similar to those reported in unacclimatized lowlanders. There was a shift to the right on AN, and maximum [La] was reduced by 7 and 8% for one- and two-leg exercises, respectively. [Epi] and [La] were tightly related (mean r = 0.81) independently of FIo2. Thus normoxia attenuated the increment in both [La] and [Epi] as a function of W, whereas the correlation between [La] and [Epi] was unaffected. These data suggest loose linkage of glycolysis to oxidative phosphorylation under influence from [Epi]. In conclusion, high-altitude natives appear to be not fundamentally different from lowlanders with regard to the effect of acute changes in FIo2 on [La] during exercise.

Adult↗
PubMed1995

A new congenital dysmegakaryopoietic thrombocytopenia (Paris-Trousseau) associated with giant platelet alpha-granules and chromosome 11 deletion at 11q23.

This study characterizes a new congenital thrombocytopenia with mild hemorrhagic tendency occurring in a woman and her child with the following features. We found a deletion of the distal part of one chromosome 11 [del(11)q23.3-->qter] that was detected by cytogenetic analysis and confirmed by chromosome painting in the two patients and also an increased number of bone marrow megakaryocytes (MKs), including numerous micromegakaryocytes (mMKs) associated with a normal platelet life span. A normal number of MK colonies in culture was observed with one third of them containing a few large MKs; however, these were always associated with mMKs identified by immunologic staining. A massive cell lysis was observed at the end of the maturation. Fifteen percent of the platelets in the peripheral blood showed giant alpha-granules resulting from the fusion of alpha-granules. These giant granules, which appeared in red on giemsa stain, had a mean diameter of 1.5 microns and showed all markers (detected at electron microscopy by immunogold method) of matrix and alpha-granule membrane, ie, von Willebrand factor, fibrinogen, CD41, CD62P (P-selectin); however, they differed from lysosomes because acid phosphatases were not present. These giant alpha-granules were unable to release their contents after stimulation by thrombin, in contrast to platelets with normal morphology. Abnormalities in bone marrow MK maturation that were detected at the electron microscopic level and that led to lysis of numerous MKs were responsible for thrombocytopenia and were similar in both patients. MK abnormalities are probably the consequence of the chromosome aberration. ETS 1 and FLI, two proto-oncogenes that appear to be essential with GATA1 for the normal expression of MK-specific genes, map to 11q23-q24 and are, thus, deleted in this thrombocytopenia. In conclusion, the association of all these abnormalities constitutes a new familial platelet disorder and may present a valuable model for exploring the role of some genes involved in the regulation of thrombopoiesis.

Adult↗