Molecular system bioenergetics: regulation of substrate supply in response to heart energy demands

This review re-evaluates regulatory aspects of substrate supply in heart. In aerobic heart, the preferred substrates are always free fatty acids, and workload-induced increase in their oxidation is observed at unchanged global levels of ATP, phosphocreatine and AMP. Here, we evaluate the mechanisms of regulation of substrate supply for mitochondrial respiration in muscle cells, and show that a system approach is useful also for revealing mechanisms of feedback signalling within the network of substrate oxidation and particularly for explaining the role of malonyl-CoA in regulation of fatty acid oxidation in cardiac muscle. This approach shows that a key regulator of fatty acid oxidation is the energy demand. Alterations in malonyl-CoA would not be the reason for, but rather the consequence of, the increased fatty acid oxidation at elevated workloads, when the level of acetyl-CoA decreases due to shifts in the kinetics of the Krebs cycle. This would make malonyl-CoA a feedback regulator that allows acyl-CoA entry into mitochondrial matrix space only when it is needed. Regulation of malonyl-CoA levels by AMPK does not seem to work as a master on–off switch, but rather as a modulator of fatty acid import.     

Permeability of 13 different gloves to 13 cytotoxic agents under controlled dynamic conditions.

PURPOSE: The permeability of 13 different gloves to 13 cytotoxic agents under controlled dynamic conditions is described. METHODS: Thirteen cytotoxic agents were prepared at the highest concentrations normally encountered by pharmacy personnel. Four glove types--neoprene, natural rubber latex, nitrile, and vinyl--were exposed to the cytotoxic agents for 15, 30, and 60 minutes. Tests were conducted using the middle finger of each glove. Linearity, reproducibility, and sensitivity were evaluated for each drug tested. Assays were run using liquid chromatographic tandem mass spectrometry (LC/MS/MS) and high-performance liquid chromatography with ultraviolet light (HPLC-UV). Permeability testing was conducted using an original system designed to evaluate dynamic constraints, such as rubbing, stretching, and tension. RESULTS: Linearity by LC/MS/MS and HPLC-UV was confirmed at concentrations up to 1000 ng/mL for all drugs. Most glove materials were permeable at rates below ASTM recommendations over the one-hour testing period. Vinyl was the most permeable material. Carmustine permeated the widest variety of materials. Due to the high sensitivity of the analytic methods, all materials displayed low but significant permeability for at least one drug after one hour. Higher resistance to permeation was recorded for all neoprene, some natural rubber latex, and one nitrile glove. CONCLUSION: Neoprene, natural rubber latex, and nitrile gloves displayed the highest resistance to permeation of the 13 cytotoxic agents studied. Additional factors, such as duration of exposure, glove thickness, and drug liposolubility and molecular weight, also affected permeability.     

Définition et évolution du statut nutritionnel au cours d'une greffe osseuse allogénique (15 malades): Rôle de la nutrition parentérale et de l'apport azoté

Our work concerned 15 patients (9 males, 6 females) with a mean age of 29.5 years, having a hematologic malignant disease and undergoing allogenic bone marrow transplantation.We studied :

1. The metabolic disorders induced by the conditioning regimen (chemotherapy and total body irradiation) pregraft accompanying cytolysis (day −7, −5, −2).

2. The corrective effect of a total parenteral nutrition introduced 2 days before the transplantation and pursued during 30 days post-graft (day −2 to day 30).

3. The interest of a high calorie intake (BEE × 2) and, after randomisation, of a variable nitrogen intake (24% of the total calorie intake for group A [8 patients] and 14% for group B [7 patients]). The patient characteristics of these two groups were closely comparable. Urinary parameters were studied daily (3-methylhistidine, cratinine, nitrogen) and blood parameters weekly (transferrin, pre-albumin, albumin, retinol binding protein).

We observed globally :

-- An excellent result of the nutritional support without significant weight loss;

-- protein catabolism stopped with a recovery of synthesis of RBP after day 7 and pre-albumin from day 7;

-- a decrease in muscle catabolism.

The randomized study showed :

-- a significant difference in nitrogen excretion between group A and group B;

-- earlier and better protein synthesis recovery in group A, particularly with regard to RBP and pre-albumin.

In conclusion, we recommend for the patients undergoing bone marrow transplantation :

-- nutritional support should be introduced before the conditioning regimen;

-- a high calorie intake (BEE × 2) with a nitrogen intake between 14% and 24% of the total calorie intake;

-- cyclic parenteral nutrition should be pursued during the second and third month post-graft.

La lame cellulo-adipeuse du creux axillaire Son intérêt anatomique,clinique, chirurgical

Résumé L'évidement axillaire peut être envisagé soit à titre préventif et systématique dans la chirurgie du cancer ou à titre curatif dans les affections du contenu de la fosse axillaire. Sa réalisation opératoire doit tenir compte de la morphologie de la lame cellulo-adipeuse de l'aisselle, moulée autour du paquet vasculo-nerveux entouré de sa gaine et de l'importance de ses prolongements vers le creux sus-claviculaire, voie de passage des courants lymphatiques.La position opératoire du membre supérieur facilite l'abord de la base de la pyramide et l'exérèse totale de son contenu sans sacrifice cutané ou musculaire et sans séquelle motrice.Le repérage des divers éléments de la lame cellulo-adipeuse doit permettre à l'anatomo-pathologiste d'apprécier la localisation exacte des ganglions lymphatiques.     

Developmental functions of mammalian Hox genes

The structure of the four murine Hox complexes and the co-ordinate expression patterns of Hox genes have been elucidated for almost a decade. However, clues about their developmental functions have been recently uncovered from the analysis of loss-of-function mutants generated by the gene targeting technique, as well as from transgenic mice with altered Hox gene expression domains. The 'anterior' Hox genes control the morphogenetic programme of specific hindbrain segments (rhombomeres) or pharyngeal arch neural crest derivatives. Various studies indicate that Hox gene products act in a region-specific, combinatorial and partly redundant manner to specify the identities of developing vertebrae. In addition, 'posterior' HoxA and HoxD genes act coordinately to control the growth and morphogenesis of skeletal structures along the proximodistal axis of developing limbs. Studies in other vertebrate model systems suggest that the evolution of Hox gene functions has allowed for the acquisition of specific morphological features along both the vertebral column and limbs of tetrapods. Gene targeting studies have also revealed region-specific functions of Hox genes along the developing digestive and genito-urinary tracts.      

Serum trace elements and myocardial infarction

The authors report trace elements concentrations (zinc, nickel, selenium, copper, manganese and chromium) during myocardial infarction described in some publication. Serum zinc decreases during the first two days after acute myocardial infarction and returns to normal level in two weeks. Serum nickel increases during the first 36 hours and copper during the first four days. The different explanations of these disturbances are also exposed.     

Overloaded training increases exercise-induced oxidative stress and damage.

We hypothesized that overloaded training (OT) in triathlon would induce oxidative stress and damage on muscle and DNA. Nine male triathletes and 6 male sedentary subjects participated in this study. Before and after a 4-week OT, triathletes exercised for a duathlon. Blood ratio of reduced vs. oxidized glutathione (GSH/GSSG), plasma thiobarbituric acid reactive substances (TBARS), leukocyte DNA damage, creatine kinase (CK), and CK-MB mass in plasma, erythrocyte superoxide dismutase (SOD) activity, erythrocyte and plasma glutathione peroxidase (GSH-Px) activities, and plasma total antioxidant status (TAS) were measured before and after OT in pre- and postexercise situations. Triathletes were overloaded in response to OT. In rest conditions, OT induced plasma GSH-Px activity increase and plasma TAS decrease (both p < 0.05). In exercise conditions, OT resulted in higher exercise-induced variations of blood GSH/GSSG ratio, TBARS level (both p < 0.05), and CK-MB mass (p < 0.01) in plasma; and decreased TAS response (p < 0.05). OT could compromise the antioxidant defense mechanism with respect to exercise-induced response. The resulting increased exercise-induced oxidative stress and further cellular susceptibility to damage needs more study.     

Skeletal muscle HSP72 response to mechanical unloading: influence of endurance training

AIMS: It has been shown that increased contractile activity results in heat shock protein 72 (HSP72) accumulation in various skeletal muscles. By contrast, there is no consensus for muscle HSP72 response to muscle disuse for short duration (5-8 days). On the basis of a greater constitutive HSP72 expression in slow-twitch muscles we tested the hypothesis that mechanical unloading for a longer period (2 weeks) would affect this phenotype to a greater extent. Secondly, we evaluated the effects of a physiological muscle heat shock protein (HSP) enhancer (endurance training) on HSP response to unloading and muscle remodelling. METHODS: Adult male Wistar rats were assigned randomly to four groups: (1) sedentary weight-bearing; (2) hindlimb-unloaded (HU) via tail suspension for 2 week; (3) trained on a treadmill (6 week) and (4) trained 6 week and then HU for 2 week. RESULTS: Unloading resulted in a preferential atrophy of slow muscles [soleus (SOL), adductor longus (AL)] and a slow-to-fast fibre transition with no change in HSP72 level. HSP72 levels were significantly lower in fast muscles [extensor digitorum longus (EDL) and plantaris (PLA)], and did not change with mechanical unloading. Endurance training was accompanied by a small (SOL) or a large (EDL, PLA) increase in HSP72 level with no change in AL. Training-induced accumulation of HSP72 disappeared with subsequent unloading in the SOL and PLA whereas HSP72 content remained elevated in EDL. CONCLUSION: The results of this study indicate that (1) after 2 weeks of unloading no change occurred in HSP72 protein levels of slow-twitch muscles despite a slow-to-fast fibre transition; and (2) the training-induced increase of HSP72 content in skeletal muscles did not attenuate fibre transition.     

Ventilatory transients during exercise: Peripheral or central control?

The fast component of the ventilatory changes that occur at the transition phases of exercise was studied in awake dogs trained to run on a treadmill. Two questions were examined: firstly, is the fast ventilatory component modified by changes in venous return to the lungs, such as those consecutive either to increased work loads or to β adrenergic blockade?, and secondly, is this component altered by central ventilatory depressants? The results showed that at the onset of exercise, there is no correlation between the instantaneous increment in ventilation and the intensity of exercise, but at the end of the readmill run, the fall in ventilation is closely linked to the power of the work performed. Ventilatory transients observed either at the start or at the end of exercise remain unaffected by administration of a β-adrenergic blocking agent. But central depressant effects on ventilation caused by narcotic analgesics or hypnotic drugs altered the breathing pattern of the fast component of exercise-induced ventilatory changes. It is concluded that the instantaneous changes in ventilation occurring at the transition phases of exercise are controlled by mechanoreceptor mechanisms, but cerebral control is superimposed on the reflex control in regulating both tidal volume and breathing rate.