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. 相似文献
Gastroesophageal reflux disease (GERD) is the most common disease of the upper gastrointestinal tract. With the introduction of proton pump inhibitors medical treatment of GERD has been significantly improved. However, the development of laparoscopic antireflux surgery resulted in an increasing interest of surgeons in this disease. An interactive meeting was organized in order to develop an agreement between gastoenterologists and surgeons regarding therapeutic decisions and this is the main topic of this paper. 相似文献
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. 相似文献
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.
Résumé
Nous avons étudié chez 15 malades (9 hommes, 6 femmes) d'âge moyen 29,5 ans, présentant une hémopathie maligne et nécessitant une greffe de moelle osseuse allogénique :
1. Les désordres métaboliques induits par la chimiothérapie et l'irradiation corporelle totale en période de prégreffe au cours de la cytolyse (J −7, J −5, J −2).
2. L'effet correcteur d'une nutrition parentérale introduite deux jours avant la greffe et exclusive durant les 30 jours post-greffe (J −2, J + 30).
3. L'intérêt d'un apport calorique élevé (BEE × 2) et, par randomisation, d'un apport azoté variable (24 % de l'apport calorique total pour le groupe A et 14 % pour le groupe B).
Nous avons étudié quotidiennement certains paramètres urinaires (3MeH, créatinine, azote) et les paramètres sanguins (transferrine, préalbumine, albumine, RBP) l'ont été de façon hebdomadaire.Nous avons constaté globalement un excellent résultat du support nutritif sans perte de poids significative, un arrêt du processus catabolique protéique avec reprise de synthèse après J +7 pour la RBP et pour la préalbumine et une réduction du catabolisme musculaire.L'étude randomisée a mis en évidence :
-- une différence statistique dans l'excrétion axotée, plus intense dans le groupe A,
-- une reprise des synthèses protéiques, plus précoce et plus performante dans ce même groupe pour la RBP et la préalbumine.
En conclusion et compte tenu de l'ensemble des éléments, nous préconisons chez ces malades devant subir une greffe de moelle osseuse allogénique :
-- une attitude préventive en ce qui concerne la nutrition à débuter avant le conditionnement,
-- un apport calorique élevé (BEE × 2) et un apport azoté situé entre 14 % et 24 % de l'apport calorique total,
-- une étude prospective quant à l'intérêt de certains acides aminés et d'une nutrition parentérale cyclique poursuivie au 2e et au 3e mois post-greffe.
Mots clés: greffe de moelle osseuse; nutrition parentérale totale; apport azotéKey-words: bone marrow transplantation; total parenteral nutrition; nitrogen intake 相似文献
Human beta-defensin 2 (DEFB4, also known as DEFB2 or hBD-2) is a salt-sensitive antimicrobial protein that is expressed in
lung epithelia. Previous work has shown that it is encoded in a cluster of beta-defensin genes at 8p23.1, which varies in
copy number between 2 and 12 in different individuals. We determined the copy number of this locus in 355 patients with cystic
fibrosis (CF), and tested for correlation between beta-defensin cluster genomic copy number and lung disease associated with
CF. No significant association was found. 相似文献
Thanatophoric dwarfism (TD) is a sporadic lethal skeletal dysplasia with
micromelic shortening of the limbs, macrocephaly, platyspondyly and reduced
thoracic cavity. In the most common subtype (TD1), femurs are curved, while
in TD2, straight femurs are associated with cloverleaf skull. Mutations in
the fibroblast growth factor receptor 3 (FGFR3) gene were identified in
both subtypes. While TD2 was accounted for by a single recurrent mutation
in the tyrosine kinase 2 domain, TD1 resulted from either stop codon
mutations or missense mutations in the extracellular domain of the gene.
Here, we report the identification of FGFR3 mutations in 25/26 TD cases.
Two novel missense mutations (Y373C and G370C) were detected in 8/26 and
1/26 TD1 cases respectively. Both mutations created cysteine residues in
the juxta extramembrane domain of the receptor. Sixteen cases carried the
previously reported R248C (9/26 cases), S249C (2/26 cases) or stop codon
FGFR3 mutations (5/26 cases). Our results suggest that TD1 is a genetically
homogeneous condition and give additional support to the view that newly
created cysteine residues in the extracellular domain of the protein play a
key role in the severity of the disease.
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