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81.
Elizabeth A. Maher Isaac Marin‐Valencia Robert M. Bachoo Tomoyuki Mashimo Jack Raisanen Kimmo J. Hatanpaa Ashish Jindal F. Mark Jeffrey Changho Choi Christopher Madden Dana Mathews Juan M. Pascual Bruce E. Mickey Craig R. Malloy Ralph J. DeBerardinis 《NMR in biomedicine》2012,25(11):1234-1244
Glioblastomas and brain metastases demonstrate avid uptake of 2‐[18F]fluoro‐2‐deoxyglucose by positron emission tomography and display perturbations of intracellular metabolite pools by 1H MRS. These observations suggest that metabolic reprogramming contributes to brain tumor growth in vivo. The Warburg effect, excess metabolism of glucose to lactate in the presence of oxygen, is a hallmark of cancer cells in culture. 2‐[18F]Fluoro‐2‐deoxyglucose‐positive tumors are assumed to metabolize glucose in a similar manner, with high rates of lactate formation relative to mitochondrial glucose oxidation, but few studies have specifically examined the metabolic fates of glucose in vivo. In particular, the capacity of human brain cancers to oxidize glucose in the tricarboxylic acid cycle is unknown. Here, we studied the metabolism of human brain tumors in situ. [U‐13 C]Glucose (uniformly labeled glucose, i.e. d ‐glucose labeled with 13 C in all six carbons) was infused during surgical resection, and tumor samples were subsequently subjected to 13C NMR spectroscopy. The analysis of tumor metabolites revealed lactate production, as expected. We also determined that pyruvate dehydrogenase, turnover of the tricarboxylic acid cycle, anaplerosis and de novo glutamine and glycine synthesis contributed significantly to the ultimate disposition of glucose carbon. Surprisingly, less than 50% of the acetyl‐coenzyme A pool was derived from blood‐borne glucose, suggesting that additional substrates contribute to tumor bioenergetics. This study illustrates a convenient approach that capitalizes on the high information content of 13C NMR spectroscopy and enables the analysis of intermediary metabolism in diverse cancers growing in their native microenvironment. Copyright © 2012 John Wiley & Sons, Ltd. 相似文献
82.
Isabel Pascual Gemma Fernández de Miguel Mariano García Arranz Damián García-Olmo 《International journal of colorectal disease》2010,25(12):1447-1451
Purpose
Use of biosutures in animal models of colonic anastomoses is associated with decreased adhesions without affecting anastomotic strength. This study aimed to evaluate the effect of biosutures on colonic anastomoses kept free of adhesions by peritoneal instillation of icodextrin 4%. 相似文献83.
Sabina Martí Gamboa Jara Pascual Mancho María Rodrigo Rodríguez Julia Ruiz Sada Sergio Castán Mateo 《The journal of maternal-fetal & neonatal medicine》2017,30(19):2367-2371
Objective: To determine which parameter of the umbilical arterial cord gas analysis, pH, base deficit (BD) or lactate has a bigger predictive ability for neonatal morbidity at term.Method: We conducted a four-year retrospective cohort study including all non-anomalous, singleton, vertex, term births with neonatal acidemia (umbilical arterial cord gas pH?≤?7.1). The primary outcomes were a composite neurological morbidity and a composite systemic morbidity. The predictive ability of lactate, BD and pH was compared using receiver operator characteristic (ROC) curves. Optimal cutoff values of lactate, BD and pH were estimated based on their maximal Youden Index.Results: We identified 466 acidemic neonates who had paired and validated cord blood gas data. The ROC curve analysis revealed that pH, BD and lactate had a similar predictive ability for neurological (AUC: 0.81; 0.78; 0.83, respectively) and systemic neonatal morbidity (AUC: 0.77; 0.82; 0.82, respectively). The combination of pH?≤?7.0 and lactate?≥?7.0?mmol/L presented similar validity to that of pH?≤?7.0 and BD?≥?12?mmol/L, but both were comparable to pH alone.Conclusions: pH, BD and lactate have similar predictive ability for adverse neonatal outcomes among acidemic neonates. Umbilical arterial lactate could replace BD as a measure of the metabolic component in acidemic neonates. However, neither BD nor lactate demonstrated in this study to improve the predictive ability of pH alone for short-term neonatal outcomes. 相似文献
84.
85.
BACKGROUND: The objective of the present study was to characterize the spectrum of circadian blood pressure changes in type I diabetes at different stages of nephropathy by using two monitorings in each patient in order to avoid intra-individual variability. PATIENTS AND METHODS: A total of 80 type I diabetic subjects and the same number of age, sex and awake mean blood pressure (BP)-matched controls were included. According to urinary albumin excretion, there were 57 normoalbuminurics, 15 persistent microalbuminurics and eight proteinurics. Two 24 h ambulatory blood pressure monitorings were performed at the same urinary albumin excretion stage in absence of antihypertensive treatment for each diabetic subject and for their respective control. Blood pressure and heart rate averages during 24 h, awake, sleep, and day: night ratio were calculated. RESULTS: Seven of the eight proteinuric subjects were hypertensives, whereas hypertension was absent in the normoalbuminuric and microalbuminuric groups. The intraindividual reproducibility in diabetics showed repeatability coefficients for the 24 h systolic and diastolic pressure of 33 and 42%, respectively. This reproducibility for the day: night ratio was generally worse, 57% for systolic and 59% for diastolic. A progressive increment in the mean ambulatory BP was observed across the three groups of diabetics and the differences in BP observed were most evident during the night-time period. Though no differences in the 24 h circadian pattern were present between the normoalbuminurics and their controls, nocturnal differences were observed, not only in microalbuminurics for systolic BP (P < 0.05), but also in proteinurics for both systolic BP (P < 0.01) as well as diastolic BP (P < 0.05). No differences were observed in heart rate among the diabetic groups. The non-dipping pattern in the two monitorings was observed in 80, 58, 18 and 10% of the proteinurics, microalbuminurics, normoalbuminurics and control groups, respectively. CONCLUSIONS: Persistent abnormal circadian variability seems to be an early and frequent characteristic of type I diabetics with an increased urinary albumin excretion. Although present in some normalbuminuric subjects, the frequency of this abnormality increases as the incipient nephropathy progresses. By the time proteinuria is established, nearly all subjects present the abnormal pattern. 相似文献
86.
Garcia-Olivé I Prats Bardají MS Calvo Pascual S Sánchez Berenguer D Valverde Forcada E Ruiz-Manzano J 《Archivos de bronconeumología》2008,44(3):170-172
Takayasu arteritis is an inflammatory disease that affects large vessels, especially the aorta and its branches. The clinical features of the disease depend on which arteries are affected. Although pulmonary artery involvement is common, only rarely is this the main clinical manifestation. We describe the case of a young woman with dyspnea who had severe pulmonary hypertension secondary to Takayasu arteritis of the pulmonary artery. She was administered corticosteroid (methylprednisolone) and immunosuppressant (azathioprine) therapy and a stent was implanted in the left pulmonary artery. Both hemodynamic and clinical signs improved. 相似文献
87.
Martínez Ara J Picazo ML Torre A Pascual D Díaz Rodríguez C Riñón C 《Nefrología : publicación oficial de la Sociedad Espa?ola Nefrologia》2000,20(4):383-386
Sclerodema renal crisis is the usual form of presentation of renal disease in systemic sclerosis. We report a woman who at age 63 was given a diagnosis of scleroderma with Raynaud's phenomenon and cutaneous, oesophageal and lung involvement but no evidence of renal disease and no treatment with D-penicillamine. Two years later she developed progressive renal failure, nephrotic range proteinuria, haematuria and the presence of serum MPO-ANCA; she was normotensive. Renal biopsy revealed extracapillary and necrotizing glomerulonephritis and skin biopsy showed leucocytoclastic vasculitis. This clinical picture was compatible with necrotizing vasculitis of the microscopic polyarterits type. After treatment with pulse steroids followed by oral steroids and monthly intravenous cyclophosphamide her renal function stabilised and the serum MPO-ANCA disappeared. 相似文献
88.
Andrea Cippitelli Jinhua Wu Kelly A Gaiolini Daniela Mercatelli Jennifer Schoch Michelle Gorman Alejandra Ramirez Roberto Ciccocioppo Taline V Khroyan Dennis Yasuda Nurulain T Zaveri Conrado Pascual Xinmin Xie Lawrence Toll 《British journal of pharmacology》2015,172(7):1834-1845
Background and Purpose
The α3β4 subtype of nicotinic acetylcholine receptors (nAChRs) has been implicated in mediating nicotine reinforcement processes. AT-1001 has been recently described as a high-affinity and selective α3β4 nAChR antagonist that blocks nicotine self-administration in rats. The aim of this study was to investigate the mechanism of action underlying the nicotine-suppressive effects of AT-1001.Experimental Approach
Effects of AT-1001 were determined using in vitro assays and rat models of nicotine addiction, and compared with varenicline.Key Results
AT-1001 and its analogue AT-1012 were functionally selective as antagonists for α3β4 over α4β2 nAChRs, but not to the same extent as the binding selectivity, and had partial agonist activity at α3β4 nAChRs. In contrast, varenicline was a partial agonist at α4β2, a weak agonist at α3β4 and inhibited α4β2 at a much lower concentration than it inhibited α3β4 nAChRs. AT-1001 and varenicline also had very different in vivo properties. Firstly, AT-1001 did not exhibit reinforcing properties per se while varenicline was self-administered. Secondly, systemic treatment with AT-1001 did not induce reinstatement of nicotine seeking but rather attenuated reinstatement induced by varenicline, as well as nicotine. Finally, unlike varenicline, AT-1001 selectively blocked nicotine self-administration without altering alcohol lever pressing as assessed in an operant co-administration paradigm.Conclusions and Implications
These findings describe a more complex AT-1001 in vitro profile than previously appreciated and provide further support for the potential of AT-1001 and congeners as clinically useful compounds for smoking cessation, with a mechanism of action distinct from currently available medications. 相似文献89.
Rosas J Ramos-Casals M Ena J García-Carrasco M Verdu J Cervera R Font J Caballero O Ingelmo M Pascual E 《Rheumatology (Oxford, England)》2002,41(6):670-675
OBJECTIVES: To examine salivary function in patients with primary Sj?gren's syndrome (SS) by assessing unstimulated and stimulated flows using 5 mg of pilocarpine in a 5% solution, in order to define their clinical usefulness in the evaluation of xerostomia in patients with primary SS as well as to identify those factors related to the increase in salivary flow after pilocarpine stimulation. METHODS: We investigated the clinical and immunological characteristics of 60 consecutive patients with primary SS. All patients fulfilled four or more of the preliminary diagnostic European criteria for SS. We measured unstimulated (basal) salivary flow (BSF) in all patients. In patients with BSF =1.5 ml, stimulated salivary flows (SSF) were also measured after stimulation with an ophthalmic 5% pilocarpine solution (0.1 ml=5 mg, administered sublingually). SSF was also measured after oral administration of 50 mg anetholetrithione (ANTT) in the same patients. These stimulated salivary flows were measured 1, 2 and 3 h after the stimulus. RESULTS: Of the 60 patients, 55 were women and five men, with a mean age at the SS onset of 61 yr (range 18-82 yr). The mean BSF for SS patients was 1.40+/-0.17 ml. Fifty (83%) patients showed a BSF less than 1.5 ml. The stimulated salivary flow after 1 h was 3.23 ml in the pilocarpine group and 0.57 in the ANTT group (P<0.001); after 2 h it was 1.32 ml in the pilocarpine group and 0.52 in the ANTT group (P=0.02) and after 3 h it was 0.80 ml in the pilocarpine group and 0.41 in the ANTT group (P=0.046). No clinical or immunological differences were found between SS patients with BSF more or less than 1.5 ml, although patients with a BSF less than 1.5 ml showed a parotid scintigraphy class III or IV more frequently (42 vs 0%, P=0.01). SS patients with a pilocarpine SSF less than 1.5 ml had a longer duration of SS (73.3 vs 31.3 months, P=0.03) and a higher prevalence of positive anti-Ro/SS-A (70 vs 36%, P=0.038), anti-La/SS-B (65 vs 32%, P=0.038), parotid scintigraphy class III-IV (79 vs 9%, P<0.001) and positive salivary gland biopsy (90 vs 43%, P<0.001). CONCLUSION: The study of xerostomia using basal and pilocarpine SSF is simple to perform, acceptable to patients and needs no special equipment. We describe a significant increase in SSF using a solution of 5% pilocarpine in comparison with salivary flow obtained after stimulation with ANTT. Twenty-two of the 46 patients with low BSF had stimulated flows over 1.5 ml. These 'responder' patients showed a shorter duration of sicca symptoms, a lower frequency of positive immunological markers and milder grades of scintigraphic patterns and lymphocytic infiltrates in salivary gland biopsies. This subset of patients probably maintain a residual capacity of their salivary glands, as opposed to the 'non-responder' patients, who had a longer duration of sicca syndrome evolution with more severe involvement of the salivary glands. 相似文献
90.
Neoadjuvant radiation and chemotherapy in rectal cancer does not increase postoperative complications 总被引:8,自引:2,他引:8
Valero G Luján JA Hernández Q De Las Heras M Pellicer E Serrano A Parrilla P 《International journal of colorectal disease》2003,18(6):495-499
Background and aims Neoadjuvant radiation and chemotherapy in rectal cancer reduces local recurrences and increases the rate of conservative sphincter surgery. However, an increase in postoperative morbidity and mortality has also been observed. This study analyzed the operative difficulty and postoperative complications in patients with this treatment.Patients and methods Retrospective review of 103 patients with rectal cancer, divided into two groups: group A, 53 patients undergoing preoperative radiotherapy with 45 Gy combined with chemotherapy, and group B, 50 patients with rectal cancer who received surgery after diagnosis. Both groups were homogeneous. The two groups were compared for both technical difficulty, using intraoperative data and rate of complications.Results There were no statistically significant differences between the two groups with regard to intraoperative or postoperative data. In group A there were 20 complications in 17 patients (32%) and in group B 22 complications in 19 patients (38%). The rates of perineal wound infection were similar. The percentage of anastomotic leaks was higher in group A. A greater number of anterior resections was performed in group A.Conclusion Preoperative radiation and chemotherapy in rectal cancer does not increase postoperative complications and increases the rate of sphincter-preserving surgery.An invited commentary on this paper is available at 相似文献