ABSTRACT
Chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH) are two forms of pulmonary hypertension (PH) characterized by obstructive vasculopathy. Endothelial dysfunction along with metabolic changes towards increased glycolysis are important in PAH pathophysiology. Less is known about such abnormalities in endothelial cells (ECs) from CTEPH patients. This study provides a systematic metabolic comparison of ECs derived from CTEPH and PAH patients. Metabolic gene expression was studied using qPCR in cultured CTEPH-EC and PAH-EC. Western blot analyses were done for HK2, LDHA, PDHA1, PDK and G6PD. Basal viability of CTEPH-EC and PAH-EC with the incubation with metabolic inhibitors was measured using colorimetric viability assays. Human pulmonary artery endothelial cells (HPAEC) were used as healthy controls. Whereas PAH-EC showed significant higher mRNA levels of GLUT1, HK2, LDHA, PDHA1 and GLUD1 metabolic enzymes compared to HPAEC, CTEPH-EC did not. Oxidative phosphorylation associated proteins had an increased expression in PAH-EC compared to CTEPH-EC and HPAEC. PAH-EC, CTEPH-EC and HPAEC presented similar HOXD macrovascular gene expression. Metabolic inhibitors showed a dose-dependent reduction in viability in all three groups, predominantly in PAH-EC. A different metabolic profile is present in CTEPH-EC compared to PAH-EC and suggests differences in molecular mechanisms important in the disease pathology and treatment.
Subject(s)
Endothelial Cells/metabolism , Pulmonary Arterial Hypertension/genetics , Pulmonary Arterial Hypertension/metabolism , Pulmonary Embolism/genetics , Pulmonary Embolism/metabolism , Adult , Aged , Cells, Cultured , Chronic Disease , Female , Gene Expression , Glutamate Dehydrogenase/genetics , Glutamate Dehydrogenase/metabolism , Glycolysis/genetics , Hexokinase/genetics , Hexokinase/metabolism , Humans , L-Lactate Dehydrogenase/genetics , L-Lactate Dehydrogenase/metabolism , Male , Middle Aged , Oxidative Phosphorylation , Pulmonary Artery/cytology , Pyruvate Dehydrogenase (Lipoamide)/genetics , Pyruvate Dehydrogenase (Lipoamide)/metabolismABSTRACT
An Amendment to this paper has been published and can be accessed via a link at the top of the paper.
ABSTRACT
Change history: In this Article, the original affiliation 2 was not applicable and has been removed. In addition, in the Acknowledgements there was a statement missing and an error in a name. These errors have been corrected online.
ABSTRACT
Carbon and other volatiles in the form of gases, fluids or mineral phases are transported from Earth's surface into the mantle at convergent margins, where the oceanic crust subducts beneath the continental crust. The efficiency of this transfer has profound implications for the nature and scale of geochemical heterogeneities in Earth's deep mantle and shallow crustal reservoirs, as well as Earth's oxidation state. However, the proportions of volatiles released from the forearc and backarc are not well constrained compared to fluxes from the volcanic arc front. Here we use helium and carbon isotope data from deeply sourced springs along two cross-arc transects to show that about 91 per cent of carbon released from the slab and mantle beneath the Costa Rican forearc is sequestered within the crust by calcite deposition. Around an additional three per cent is incorporated into the biomass through microbial chemolithoautotrophy, whereby microbes assimilate inorganic carbon into biomass. We estimate that between 1.2 × 108 and 1.3 × 1010 moles of carbon dioxide per year are released from the slab beneath the forearc, and thus up to about 19 per cent less carbon is being transferred into Earth's deep mantle than previously estimated.
Subject(s)
Carbon Dioxide/analysis , Carbon Sequestration , Geologic Sediments/chemistry , Biomass , Carbon Isotopes , Costa Rica , Geologic Sediments/microbiology , HeliumABSTRACT
No disponible
Subject(s)
Humans , Female , Middle Aged , Pancreatitis/chemically induced , Azithromycin/adverse effects , Diagnosis, DifferentialSubject(s)
Anti-Bacterial Agents/adverse effects , Azithromycin/adverse effects , Pancreatitis/chemically induced , Acute Disease , Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Causality , Female , Humans , Middle Aged , Recurrence , Respiratory Tract Infections/drug therapyABSTRACT
Melt electrospinning is an emerging fiber-based manufacturing technique that can be used to design and build scaffolds suitable for many tissue engineering (TE) applications. Contrary to the widely used solution electrospinning, the melt process is solvent-free and therefore volatility and toxicity issues associated with solvents can be avoided. Furthermore, molten polymers are often viscous and nonconductive, making them candidates for generating electrospinning jets without electrical instabilities. This in turn permits a precise and predictable fiber deposition in the combination with moving collectors, termed melt electrospinning writing (MEW), allows the layer-by-layer fabrication of small to large volume scaffolds with specific designs, shapes and thicknesses. In vitro studies have demonstrated that scaffolds designed and fabricated via MEW can support cell attachment, proliferation and extracellular matrix formation, as well as cell infiltration throughout the thickness of the scaffold facilitated by the large pores and pore interconnectivity. Moreover, in vivo studies show that scaffolds designed for specific tissue regeneration strategies performed superbly. This review describes the state-of-the-art and unique perspectives of melt electrospinning and its writing applied to scaffold-based TE.
Subject(s)
Biocompatible Materials , Tissue Engineering/methods , Tissue Scaffolds , Animals , Humans , Tissue Engineering/instrumentationABSTRACT
The aqueous extraction of the sesquiterpene lactone xanthatin from Xanthium spinosum L. favours the conversion of xanthinin (1) to xanthatin (2) via the loss of acetic acid. The cytotoxic (Hep-G2 and L1210 human cell lines) and antiviral activities of isolated xanthatin are established. This natural compound shows significant cytotoxicity against the Hep-G2 cell line and our experimental results reveal its strong anti-angiogenesis capacity in vitro. The structure of xanthatin is determined by spectroscopic methods and for the first time confirmed by X-ray diffraction.
Subject(s)
Angiogenesis Inhibitors/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Antiviral Agents/pharmacology , Furans/pharmacology , Neovascularization, Pathologic/drug therapy , Viruses/drug effects , Xanthium/chemistry , Angiogenesis Inhibitors/chemistry , Angiogenesis Inhibitors/isolation & purification , Animals , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Antiviral Agents/chemistry , Antiviral Agents/isolation & purification , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Furans/chemistry , Furans/isolation & purification , Hep G2 Cells , Humans , Mice , Microbial Sensitivity Tests , Molecular Conformation , Rats , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
Diet has a significant impact on colorectal cancer and both dietary fiber and plant-derived compounds have been independently shown to be inversely related to colon cancer risk. Butyrate (NaB), one of the principal products of dietary fiber fermentation, induces differentiation of colon cancer cell lines by inhibiting histone deacetylases (HDACs). On the other hand, (-)-epicatechin (EC) and (-)-epigallocatechin gallate (EGCG), two abundant phenolic compounds of green tea, have been shown to exhibit antitumoral properties. In this study we used colon cancer cell lines to study the cellular and molecular events that take place during co-treatment with NaB, EC and EGCG. We found that (i) polyphenols EC and EGCG fail to induce differentiation of colon adenocarcinoma cell lines; (ii) polyphenols EC and EGCG reduce NaB-induced differentiation; (iii) the effect of the polyphenols is specific for NaB, since differentiation induced by other agents, such as trichostatin A (TSA), was unaltered upon EC and EGCG treatment, and (iv) is independent of the HDAC inhibitory activity of NaB. Also, (v) polyphenols partially reduce cellular NaB; and (vi) on a molecular level, reduction of cellular NaB uptake by polyphenols is achieved by impairing the capacity of NaB to relocalize its own transporter (monocarboxylate transporter 1, MCT1) in the plasma membrane. Our findings suggest that beneficial effects of NaB on colorectal cancer may be reduced by green tea phenolic supplementation. This valuable information should be of assistance in choosing a rational design for more effective diet-driven therapeutic interventions in the prevention or treatment of colorectal cancer.
Subject(s)
Butyric Acid/pharmacology , Catechin/analogs & derivatives , Catechin/pharmacology , Cell Differentiation/drug effects , Colonic Neoplasms/drug therapy , Monocarboxylic Acid Transporters/metabolism , Polyphenols/pharmacology , Tea/chemistry , Adenocarcinoma/drug therapy , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Alkaline Phosphatase/metabolism , Anticarcinogenic Agents/pharmacology , Apoptosis/drug effects , Blotting, Western , Cell Membrane/drug effects , Cell Membrane/metabolism , Cell Proliferation/drug effects , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Histamine Antagonists/pharmacology , Humans , Membrane Microdomains/drug effects , Membrane Microdomains/metabolism , Tumor Cells, CulturedABSTRACT
OBJECTIVES: Laparoscopic bariatric surgery is a challenge for anesthesiologists because morbidly obese patients are at high risk and laparoscopy may complicate respiratory and hemodynamic management. The aim of this study was to analyze the perioperative anesthetic management of morbidly obese patents undergoing laparoscopic bariatric surgery. MATERIAL AND METHODS: Prospective study of 300 consecutive patients diagnosed with morbid obesity and scheduled for laparoscopic bariatric surgery. Patients were positioned with a wedge cushion under the head and shoulders. A rapid sequence induction of anesthesia was carried out. A short-handled, articulated-blade McCoy laryngoscope was used for intubation; an intubation laryngeal mask airway (Fastrach) was on hand as a rescue device. Propofol and remifentanil were used for maintenance of anesthesia and morphine was administered at the end of surgery. Incentive spirometry was initiated in the postanesthetic recovery unit. RESULTS: Eighty percent of the patients were women with a mean (SD) body mass index (kg/m2) of 46 (5). The first choice of direct laryngoscopic intubation was successful in 98.6% of cases. All patients were successfully intubated. Only 5 patients required intensive care. Postoperative complications (mainly respiratory problems, bleeding, and infections) were observed in 17%. No patient died. CONCLUSIONS: Perianesthetic management of morbidly obese patients who undergo laparoscopic surgery is safe. To minimize pulmonary complications, preoxygenation and rapid sequence induction should be performed correctly and incentive spirometry should be initiated in the immediate postoperative period. The McCoy laryngoscope ensures intubation in most cases.
Subject(s)
Airway Management/methods , Bariatric Surgery/methods , Laparoscopy/methods , Obesity, Morbid/surgery , Perioperative Care/methods , Adolescent , Adult , Aged , Analgesics/therapeutic use , Anesthesia, Intravenous/methods , Anesthetics, Intravenous/administration & dosage , Female , Hemodynamics , Humans , Intubation, Intratracheal/instrumentation , Intubation, Intratracheal/methods , Laryngeal Masks , Laryngoscopes , Male , Middle Aged , Obesity, Morbid/physiopathology , Oxygen Inhalation Therapy , Pain, Postoperative/drug therapy , Pneumoperitoneum, Artificial/methods , Postoperative Complications/prevention & control , Prospective Studies , Risk , Spirometry , Young AdultABSTRACT
Objetivos: La cirugía bariátrica laparoscópica supone un reto para el anestesiólogo, ya que el obeso mórbido es un paciente de alto riesgo y la laparoscopia puede dificultar el tratamiento ventilatorio y hemodinámico del paciente. El objetivo de este estudio es analizar el tratamiento perioperatorio anestésico de pacientes obesos mórbidos sometidos a cirugía bariátrica laparoscópica. Material y métodos: Estudio prospectivo de 300 pacientes consecutivos diagnosticados de obesidad mórbida, programados para cirugía bariátrica por laparoscopia. Los pacientes se posicionaron con almohadillado en cuña bajo cabeza y hombros. Se llevó a cabo una inducción anestésica de secuencia rápida. Para la intubación se utilizó un laringoscopio de mango corto y pala articulada (McCoy), utilizando de rescate la ILMA (intubation laryngeal mask airway) o Fastrach. El mantenimiento anestésico se realizó con propofol y remifentanilo, administrando cloruro mórfico al final de la cirugía. En la unidad de reanimación postanestésica se inició espirometría incentivada. Resultados: El 80% fueron mujeres, con un índice de masa corporal de 46 ± 5 Kg/m2. Se utilizó de primera elección laringoscopia directa para intubar en el 98,6% de los casos. Ningún paciente fue imposible de intubar. Sólo 5 pacientes precisaron cuidados intensivos. Hubo un 17% de complicaciones postoperatorias, destacando las respiratorias, hemorrágicas e infecciosas. No hubo ningún caso de mortalidad. Conclusión: El manejo perianestésico de pacientes con obesidad mórbida operados mediante abordaje laparoscópico es seguro. Para minimizar las complicaciones respiratorias, conviene: preoxigenar adecuadamente, realizar inducción de secuencia rápida y comenzar la espirometría incentivada en el postoperatorio inmediato. El laringoscopio de McCoy garantiza la intubación en la mayoría de los casos(AU)
Objectives: Laparoscopic bariatric surgery is a challenge for anesthesiologists because morbidly obese patients are at high risk and laparoscopy may complicate respiratory and hemodynamic management. The aim of this study was to analyze the perioperative anesthetic management of morbidly obese patients undergoing laparoscopic bariatric surgery. Material and methods: Prospective study of 300 consecutive patients diagnosed with morbid obesity and scheduled for laparoscopic bariatric surgery. Patients were positioned with a wedge cushion under the head and shoulders. A rapid sequence induction of anesthesia was carried out. A short-handled, articulated-blade McCoy laryngoscope was used for intubation; an intubation laryngeal mask airway (Fastrach) was on hand as a rescue device. Propofol and remifentanil were used for maintenance of anesthesia and morphine was administered at the end of surgery. Incentive spirometry was initiated in the postanesthetic recovery unit. Results: Eighty percent of the patients were women with a mean (SD) body mass index (kg/m2) of 46 (5). The first choice of direct laryngoscopic intubation was successful in 98.6% of cases. All patients were successfully intubated. Only 5 patients required intensive care. Postoperative complications (mainly respiratory problems, bleeding, and infections) were observed in 17%. No patient died. Conclusions: Perianesthetic management of morbidly obese patients who undergo laparoscopic surgery is safe. To minimize pulmonary complications, preoxygenation and rapid sequence induction should be performed correctly and incentive spirometry should be initiated in the immediate postoperative period. The McCoy laryngoscope ensures intubation in most cases(AU)
Subject(s)
Humans , Male , Female , Adolescent , Adult , Middle Aged , Anesthesia/methods , Anesthesia/statistics & numerical data , Obesity, Morbid/diagnosis , Obesity, Morbid/drug therapy , Obesity, Morbid/surgery , Bariatric Surgery/methods , Laparoscopy/methods , Preoperative Care/methods , Anesthesia, General/methods , Propofol/therapeutic use , Obesity, Morbid/physiopathology , Anesthesia, General/trends , Anesthesia, General , Pneumoperitoneum/drug therapy , Pneumoperitoneum/surgery , Prospective Studies , Ranitidine/therapeutic use , Midazolam/therapeutic use , Postoperative Complications/drug therapyABSTRACT
The authors explain the effects introducing workshops for laughter therapy and relaxation to a unit dedicated to therapeutic education and functional rehabilitation; the authors test to see if the application of this therapy helps to decrease pain, to improve mobility and to reduce an altered emotional state, such as anxiety-depression, common among chronic pain patients.
Subject(s)
Laughter Therapy , Pain Management , Adult , Aged , Chronic Disease , Female , Humans , Middle Aged , Musculoskeletal Diseases/complications , Pain/etiologyABSTRACT
Se explican los efectos de la introducción de talleres de risoterapia y relajación en una unidad de educación terapéutica y rehabilitación funcional, y se comprueba si su aplicación ayuda a disminuir el dolor, mejorar la movilidad y reducir el estado emocional alterado (ansiedad-depresión) del paciente(AU)
The authors explain the effects introducing workshops for laughter therapy and relaxation to a unit dedicated to therapeutic education and functional rehabilitation; the authors test to see if the application of this therapy hepls to decrease pain, to improve mobility and to reduce na altered emotional state, such as anxiety-depression, common among chronic pain patients(AU)
Subject(s)
Humans , Female , Middle Aged , Laughter Therapy/nursing , Pain/nursing , Pain/therapy , Relaxation/physiology , Relaxation/psychology , Anxiety/nursing , Anxiety Disorders/nursing , Spinal Diseases/nursing , Spinal Diseases/psychology , Laughter Therapy/statistics & numerical data , Laughter Therapy/standards , Pain/psychology , Musculoskeletal System/pathology , Mobility Limitation , Affective Disorders, Psychotic/nursing , Wit and Humor as Topic/psychology , Mood Disorders/nursingABSTRACT
BACKGROUND: Tuberculosis (TB) continues to be an important health problem, in many cases the Hospital Emergency Services (HES) are the first contact of the patients with the sanitary system, there is not known the impact of this disease in the above mentioned services. The objectives of this study are to know the importance of TB in HES and to describe hospital discharges (MBDS) with TB diagnosis and if they had already been diagnosed in the HES. METHODS: A retrospective descriptive study of discharges with TB diagnosis in the hospital ward and in the HES of a tertiary care university hospital from 2002 to 2006. The Diagnostic concordance study and analysis of variables according to two groups: Coincidents (discharge with TB diagnosis in the HES and in the MBDS) and Only in the MBDS. Calculate statisticals of central tendency and dispersal for the quantitative variables and proportions and tables of contingency with application of the test chi(2) for the qualitative ones. RESULTS: Of the 172 (0.26%) emergencies admitted which were hospital discharges with Tb diagnosis, 61(35.5%) came in HES. The diagnostic concordance was 0.43(43.66%). The hospital discharges with Tb diagnosis (coincidents) changed from 47 (17) in 2002 to 21(5) in 2006. The 65.1% (68.9% in coincidents) were males. As regards age groups (coincidents%): 0-14: 6 (33.3%), 15-45: 81(47%), 46-65: 46(28.7%), 65: 39(19.7%); excluding group 0-14, p=0.009. Respiratory location (coincidents): 110 (50) and positive direct examination of smears for acid-fast bacilli (coincidents): 87 (43). Between well-known risk factors immigration stands out (p=0.001). CONCLUSIONS: The discharges with TB diagnosis declined during the period studied. The diagnostic concordance in the HES was moderate. We would have to insist more on seniors, and in people with well-known risk factors. In the HES the respiratory TB is also the most frequent being the direct examination of smears for acid-fast bacilli the principal diagnostic method.
Subject(s)
Emergency Service, Hospital , Patient Discharge , Tuberculosis/epidemiology , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Retrospective Studies , Spain/epidemiology , Tuberculosis/diagnosis , Young AdultABSTRACT
The biochemical effects of training programmes have been studied with a kinetic model of central metabolism, using enzyme activities and metabolite concentrations measured at rest and after 30 s maximum-intensity exercise, collected before and after long and short periods of training, which differed only by the duration of the rest intervals. After short periods of training the glycolytic flux at rest was three times higher than it had been before training, whereas during exercise the flux and energy consumption remained the same as before training. Long periods of training had less effect on the glycolytic flux at rest, but increased it in response to exercise, increasing the contribution of oxidative phosphorylation.
Subject(s)
Energy Metabolism/physiology , Exercise/physiology , Models, Biological , Muscle, Skeletal/metabolism , Algorithms , Glycolysis/physiology , Humans , Muscle, Skeletal/physiology , Time FactorsABSTRACT
Grape (Vitis vinifera) and pine (Pinus pinaster) bark extracts are widely used as nutritional supplements. Procyanidin-rich fractions from grape and pine bark extract showing different mean degrees of polymerization, percentage of galloylation (percentage of gallate esters) and reactive oxygen species-scavenging capacity were tested on HT29 human colon cancer cells. We observed that the most efficient fractions in inhibiting cell proliferation, arresting the cell cycle in G(2) phase and inducing apoptosis were the grape fractions with the highest percentage of galloylation and mean degree of polymerization. Additionally, the antiproliferative effects of grape fractions were consistent with their oxygen radical-scavenging capacity and their ability to trigger DNA condensation-fragmentation.
Subject(s)
Biflavonoids/chemistry , Catechin/chemistry , Cell Cycle/drug effects , Pinus/chemistry , Proanthocyanidins/chemistry , Tissue Extracts/chemistry , Tissue Extracts/pharmacology , Vitis/chemistry , Animals , Apoptosis/drug effects , Biopolymers/chemistry , Cell Line , Cell Proliferation/drug effects , HT29 Cells , Humans , Molecular Structure , Plant Bark/chemistry , RatsABSTRACT
Fractionation of the cyclohexane extract from the stem bark powder of Zanthoxylum madagascariense led to the isolation of a new benzophenanthridine-type alkaloid, hydrochloride of 2,3-methylendioxy-8-hydroxy- 7-methoxy-benzo[C]phenanthridine (Rutaceline), characterized on the basis of its spectral data. Rutaceline was evaluated for its antiproliferative capacity on the human colorectal adenocarcinoma (Caco-2) and the African green monkey kidney (Vero) cell lines. The 50% inhibition of cell growth (IC50) obtained after 24 h incubation was similar for both cells lines (110-115 microg/ml, i.e. 269-281 microM), but at 48 h the IC50 value for the Caco-2 cells was lower than for the Vero cells (20 microg/lml, i.e. 49 microM versus 90 microg/ml, i.e. 220 microM) indicating a higher cell growth inhibitory effect on the colon adenocarcinoma cells. At the respective IC50 concentrations, Rutaceline did not significantly induce apoptosis but induced cell cycle arrest in the GO/G1 phase, as well as a decrease of cells in S phase. Rutaceline also induced DNA fragmentation in both cell lines, as revealed by agarose gel electrophoresis, and a dose-dependent clastogenic effect in both cell lines as revealed by the Comet assay.
Subject(s)
Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Benzophenanthridines/isolation & purification , Benzophenanthridines/pharmacology , Zanthoxylum , Adenocarcinoma , Animals , Antineoplastic Agents/chemistry , Benzophenanthridines/chemistry , Cell Line , Cell Line, Tumor , Chlorocebus aethiops , Colorectal Neoplasms , Humans , Kidney/drug effects , Kinetics , Madagascar , Vero CellsABSTRACT
This work shows the properties of grape procyanidins with additional anticarcinogenic properties for increasing the shelf life of functional seafood preparations. Galloylated procyanidins (100 ppm, 2.7 mean degree of polymerization, 25% galloylation) extended the shelf life of minced horse mackerel muscle stored at 4 degrees C more than 8 days compared to controls without addition of polyphenols. The levels of endogenous alpha-tocopherol, EPA, and DHA of fish muscle were also preserved after 10 days at 4 degrees C. Therefore, the presence of procyanidins increased the stability of a product based on minced fish muscle during cold storage and maintained its functionality associated with the presence of polyunsaturated fatty acids and alpha-tocopherol. In addition, grape procyanidins showed a significant capacity to induce apoptosis in colon cancer cells (HT29 cell line) while being inactive in noncancer control cells (IEC-6). Thus, the product based on fatty fish muscle supplemented with grape procyanidins appears to be a stable functional food offering the combined action of omega-3 fatty acids and natural polyphenols.
Subject(s)
Antineoplastic Agents, Phytogenic/therapeutic use , Antioxidants , Colonic Neoplasms/drug therapy , Dietary Fats/standards , Proanthocyanidins/therapeutic use , Seafood , Vitis , Animals , Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Cell Line , Cell Line, Tumor , Colon/drug effects , Dietary Supplements , Fishes , Food Preservation/methods , Humans , Phytotherapy , Proanthocyanidins/pharmacologyABSTRACT
Inhibitors of glycogen breakdown regulate glucose homeostasis by limiting glucose production in diabetes. Here we demonstrate that restrained glycogen breakdown also inhibits cancer cell proliferation and induces apoptosis through limiting glucose oxidation, as well as nucleic acid and de novo fatty acid synthesis. Increasing doses (50-100 microM) of the glycogen phosphorylase inhibitor CP-320626 inhibited [1,2-(13)C(2)]glucose stable isotope substrate re-distribution among glycolysis, pentose and de novo fatty acid synthesis in MIA pancreatic adenocarcinoma cells. Limited oxidative pentose-phosphate synthesis, glucose contribution to acetyl CoA and de novo fatty acid synthesis closely correlated with decreased cell proliferation. The stable isotope-based dynamic metabolic profile of MIA cells indicated a significant dose-dependent decrease in macromolecule synthesis, which was detected at lower drug doses and before the appearance of apoptosis markers. Normal fibroblasts (CRL-1501) did not show morphological or metabolic signs of apoptosis likely due to their slow rate of growth and metabolic activity. This indicates that limiting carbon re-cycling and rapid substrate mobilisation from glycogen may be an effective and selective target site for new drug development in rapidly dividing cancer cells. In conclusion, pancreatic cancer cell growth arrest and death are closely associated with a characteristic decrease in glycogen breakdown and glucose carbon re-distribution towards RNA/DNA and fatty acids during CP-320626 treatment.