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61.
Liliana Lucescu Alina Ghinet Sergiu Shova Romain Magnez Xavier Thuru Amaury Farce Benoît Rigo Dalila Belei Joëlle Dubois Elena Bîcu 《Archiv der Pharmazie》2019,352(5)
Unprecedented triazinyl‐isoxazoles were afforded via an effective cycloaddition reaction between nitrile oxides and the scarcely described 2‐ethynyl‐4,6‐dimethoxy‐1,3,5‐triazine as dipolarophile. The biological evaluation of the newly synthesized compounds showed that the inhibition of human farnesyltransferase by zinc complexation could be improved with triazine‐isoxazole moieties. The replacement of the isoxazole unit by a pyrrolidin‐2‐one was detrimental to the inhibitory activity while the pyrrolidin‐2‐thione derivatives conserved the biological potential. The potential of selected compounds to disrupt protein farnesylation in Chinese hamster ovary (CHO) cells transfected with pEGFP‐CAAX was also evaluated. 相似文献
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da Silveira Fd Lopes Bde A da Fonseca CO Quirico-Santos T de Palmer Paixão IC de Amorim LM 《Journal of cancer research and clinical oncology》2012,138(8):1347-1354
Purpose
Malignant gliomas are associated with alteration in EGF/EGFR signaling. Functional EGF+61A>G polymorphism is implicated with risk, recurrence, and progression of glioma. This study aimed to establish a putative association of EGF+61A>G with risk of glioma development, production of angiogenic growth factor EGF, and the response to perillyl alcohol administered by intranasal route.Methods
The study included 83 patients with recurrent glioma enrolled in Phase I/II trial for intranasal perillyl alcohol therapy and subjects without cancer (n?=?196) as control group. DNA was extracted from blood samples, EGF genotype performed with PCR–RFLP assay, and EGF circulating levels by enzyme immunoassay. Adequate statistical tests were performed to verify associations between polymorphism and glioma risk, and genotype correlation with EGF circulating levels. The log-rank test was also used to evaluate differences on patient survival.Results
Patients with primary glioblastoma had high frequency of AA genotype (p?=?0.037) and A allele (p?=?0.037). Increased EGF circulating levels were observed in glioma patients with AA (p?=?0.042), AG (p?=?0.006), and AA?+?AG (p?=?0.008) genotypes compared with GG. Patients with GG genotype showed increased but not significant (p?>?0.05) survival rate, and EGF levels lower than 250?pg/mL was consistently (p?=?0.0374) associated with increased survival.Conclusion
Presence of EGF+61A>G polymorphism in Brazilian subjects was associated with glioma risk and increased circulating EGF levels. Better response to perillyl alcohol-based therapy was observed in a group of adult Brazilian subjects with lower EGF levels. 相似文献66.
Giancarlo Di Gennaro Alfredo D’Aniello Marco De Risi Pier Paolo Quarato Addolorata Mascia Liliana G. Grammaldo Giulio N. Meldolesi Vincenzo Esposito Elisa Fabi Angelo Picardi 《Clinical neurophysiology》2013,124(8):1536-1540
ObjectiveThis study aims to assess the prognostic value of acute postoperative seizures (APOS) in patients surgically treated for drug-resistant extra-temporal lobe (ET) epilepsy.MethodsWe studied 77 consecutive patients with ET epilepsy who underwent epilepsy surgery and were followed up for at least 2 years (mean duration of follow-up 6.2 years, range 2–14). Medical charts were reviewed to identify APOS, defined as ictal events with the exception of auras occurring within the first 7 days after surgery. Seizure outcome was determined at annual intervals. Patients who were in Engel Class I at the last contact were classified as having a favourable outcome.ResultsSeizure outcome was favourable in 47 patients (61%). The occurrence of APOS and incompleteness of resection were found to be independently associated with unfavourable outcome in a multiple regression model including all preoperative factors identified as outcome predictors in univariate analysis. Duration of illness was the only independent preoperative predictor of APOS.ConclusionsOur study suggests that APOS may predict long-term outcome in patients undergoing resective surgery for ET epilepsy. Given some study limitations, our findings should be regarded as preliminary and need confirmation from future larger, prospective, multicentre studies.SignificanceCaution may be required in the clinical management of patients experiencing APOS. 相似文献
67.
Giulio Perugi Michele Poletti Chiara Logi Caterina Berti Anna Romano Paolo Del Dotto Claudio Lucetti Roberto Ceravolo Liliana Dell’Osso Ubaldo Bonuccelli 《Neurological sciences》2013,34(9):1537-1541
Patients with Parkinson’s disease (PD) may present delusional jealousy (DJ). In a previous cross-sectional prevalence study we identified 15 cognitively preserved and five demented PD patients with DJ. The current study aimed at evaluating their clinical (motor and non-motor) characteristics and the pharmacological treatments associated with DJ, and its subsequent pharmacological management. Patients were assessed by neurologists and psychiatrists using the Hoehn and Yahr scale, the Unified Parkinson’s Disease Rating Scale, the Brief Psychiatric Rating Scale, the Beck Depression Inventory, the Hamilton Anxiety Scale and the Neuropsychiatric Inventory. Efficacy of DJ management was evaluated in follow-up visits. All patients were in therapy with dopamine agonists. A subgroup of five cognitively preserved patients developed DJ after a short period of treatment of therapy with dopamine agonists, while other patients developed DJ after a longer period of dopaminergic treatment. Psychiatric comorbidities were common in cognitively preserved and in demented patients. The pharmacological management included the interruption of dopamine agonists in two patients and the reduction of dopamine agonist dose plus the use of antipsychotics in other patients. These clinical data suggest that the management of medicated PD patients should include investigation for the presence of DJ and the evaluation of clinical characteristics potentially relevant to the prevention or the early recognition of delusions. 相似文献
68.
Francisco Javier Guzmán-de la Garza Juan Manuel Ibarra-Hernández Paula Cordero-Pérez Pablo Villegas-Quintero Claudia Ivette Villarreal-Ovalle Liliana Torres-González Norma Edith Oliva-Sosa Gabriela Alarcón-Galván Nancy Esthela Fernández-Garza Linda Elsa Mu?oz-Espinosa Carlos Rodrigo Cámara-Lemarroy José Gerardo Carrillo-Arriaga 《Clinics (S?o Paulo, Brazil)》2013,68(7):1034-1038
OBJECTIVE:
It is essential to identify a serological marker of injury in order to study the pathophysiology of intestinal ischemia reperfusion. In this work, we studied the evolution of several serological markers after intestinal ischemia reperfusion injury in rats. The markers of non-specific cell damage were aspartate aminotransferase, alanine aminotransaminase, and lactic dehydrogenase, the markers of inflammation were tumor necrosis factor alpha, interleukin-6, and interleukin-1 beta, and the markers of intestinal mucosal damage were intestinal fatty acid binding protein and D-lactate. We used Chiús classification to grade the histopathological damage.METHODS:
We studied 35 Wistar rats divided into groups according to reperfusion time. The superior mesenteric artery was clamped for 30 minutes, and blood and biopsies were collected at 1, 3, 6, 12, 24, and 48 hours after reperfusion. We plotted the mean ± standard deviation and compared the baseline and maximum values for each marker using Student''s t-test.RESULTS:
The maximum values of interleukin-1 beta and lactic dehydrogenase were present before the maximal histopathological damage. The maximum tumor necrosis factor alpha and D-lactate expressions coincided with histopathological damage. Alanine aminotransaminase and aspartate aminotransferase had a maximum expression level that increased following the histopathological damage. The maximum expressions of interluken-6 and intestinal fatty acid binding protein were not significantly different from the Sham treated group.CONCLUSION:
For the evaluation of injury secondary to acute intestinal ischemia reperfusion with a 30 minute ischemia period, we recommend performing histopathological grading, quantification of D-lactate, which is synthesized by intestinal bacteria and is considered an indicator of mucosal injury, and quantification of tumor necrosis factor alpha as indicators of acute inflammation three hours after reperfusion. 相似文献69.
70.
Gheorghiade M Pang PS Ambrosy AP Lan G Schmidt P Filippatos G Konstam M Swedberg K Cook T Traver B Maggioni A Burnett J Grinfeld L Udelson J Zannad F 《Heart failure reviews》2012,17(3):485-509
Hospitalization for worsening chronic heart failure results in high post-discharge mortality, morbidity, and cost. However, thorough characterization, soon after discharge of patients with early post-discharge events has not been previously performed. The objectives of this study were to describe the baseline, in-hospital, and post-discharge clinical, laboratory, and neurohormonal profiles of patients hospitalized for worsening heart failure with reduced ejection fraction (EF) who die or are re-admitted for cardiovascular (CV) causes within 90 days of initial hospitalization. Retrospective analysis of 4,133 patients hospitalized for worsening heart failure with EF ≤40% in the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan (EVEREST) trial, which randomized patients to tolvaptan or placebo, both in addition to standard therapy. Clinical and laboratory parameters were obtained within 48?h of admission, during hospitalization, and post-discharge weeks 1, 4, 8, and every 8?weeks thereafter for a median of 9.9?months. Patients with events within 90?days were compared with those with later/no events. All-cause mortality (ACM) and CV re-hospitalization were independently adjudicated. Within 90?days of admission, 395 patients (9.6%) died and 801 patients (19.4%) were re-hospitalized for CV causes. Significant baseline and longitudinal differences were seen between groups with early versus later (>90?days) or no events at 12?months post-randomization. Post-discharge outcomes were similar in the tolvaptan and placebo groups. Patients with early post-discharge events experienced clinically significant worsening in signs and symptoms, laboratory values, and neurohormonal parameters soon after discharge. Identifying these abnormalities may facilitate efforts to reduce post-discharge mortality and re-hospitalization. 相似文献