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101.
Adelaide Maria de Souza Antunes Rafaela Di Sabato Guerrante Jorge de Paula Costa Ávila Flavia Maria Lins Mendes Iolanda M. Fierro 《Expert opinion on therapeutic patents》2016,26(12):1449-1457
Introduction: Arterial hypertension affects over one billion people around the world, making the prevention and treatment of this disease vital. Despite the efforts made to develop new antihypertensive drugs, few new therapies have become available. Angiotensin-converting enzyme (ACE) inhibitors have heralded major steps forward in the treatment of arterial hypertension and cardiovascular diseases since the first compound of this class, captopril, was approved for clinical use in 1981.Areas covered: In this review, the authors investigated the patent documents that cite the priority patent for captopril, Squibb’s first blockbuster, or any other patent from its patent family. The documents were classified into the following: new compounds, new compositions, treatment, process (preparation of a compound), use of a compound, and process for the preparation of an intermediate. Therefore, the readers can identify potential innovations in the field.Expert opinion: The pharmaceutical sector has attempted to provide significant technological developments on anti-hypertensive drugs based on the patenting of captopril, including the development of new compositions further comprising an ACE inhibitor and other antihypertensive agent, along with dual action compounds, novel molecules with dual activity. The target is to find a new agent with better blood pressure-lowering efficacy, improved safety and good tolerability pro?le. 相似文献
102.
Prevalence of comorbidities in patients with obstructive sleep apnea syndrome,overlap syndrome and obesity hypoventilation syndrome
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Santaniello S Burns SP Golby AJ Singer JM Anderson WS Sarma SV 《Epilepsy & behavior : E&B》2011,22(Z1):S49-S60
Epilepsy affects 50 million people worldwide, and seizures in 30% of the cases remain drug resistant. This has increased interest in responsive neurostimulation, which is most effective when administered during seizure onset. We propose a novel framework for seizure onset detection that involves (i) constructing statistics from multichannel intracranial EEG (iEEG) to distinguish nonictal versus ictal states; (ii) modeling the dynamics of these statistics in each state and the state transitions; you can remove this word if there is no room. (iii) developing an optimal control-based "quickest detection" (QD) strategy to estimate the transition times from nonictal to ictal states from sequential iEEG measurements. The QD strategy minimizes a cost function of detection delay and false positive probability. The solution is a threshold that non-monotonically decreases over time and avoids responding to rare events that normally trigger false positives. We applied QD to four drug resistant epileptic patients (168 hour continuous recordings, 26-44 electrodes, 33 seizures) and achieved 100% sensitivity with low false positive rates (0.16 false positive/hour). This article is part of a Supplemental Special Issue entitled The Future of Automated Seizure Detection and Prediction. 相似文献
107.
Carpagnano GE Resta O Pergola GD Sabato R Foschino Barbaro MP 《Journal of breath research》2010,4(3):036003
Leptin plays a key role in obstructive sleep apnea syndrome (OSAS). Leptin production in human airways has been previously evaluated by measuring leptin concentration in the exhaled breath condensate and in the induced sputum. The aim was to study leptin expression in the cells of induced sputum and in exhaled breath condensate of subjects with OSAS. Moreover, leptin concentrations in the blood were measured in the same groups of subjects. We enrolled four groups of patients: (1) obese patients with OSAS (OO); (2) non-obese patients with OSAS (NOO); (3) obese patients without OSAS (ONO); and (4) non-obese subjects without OSAS (C). Leptin expression was evaluated by immunocytochemistry in the sputum cells of the enrolled subjects. The concentrations of leptin in the exhaled breath condensate and plasma were measured by using a specific enzyme immunoassay. Leptin protein expression and the percentage of macrophages and neutrophils expressing leptin were higher in the induced sputum of OO, NOO and ONO patients than in C. Leptin concentrations in the exhaled breath condensate were significantly higher in OO patients (5.12 (3.8-6.6) ng ml(-1)) than in NOO (4.1 (3.9-5.2) ng ml(-1)) and ONO (4.2 (3.6-5.0) ng ml(-1)) patients. The concentration of leptin in plasma was significantly more elevated in OO (36 (24-65.9) ng ml(-1)) than in NOO (30.2 (12.4-51.4) ng ml(-1)), whereas it was not significantly different in ONO patients. This study showed that leptin in sputum and in the exhaled breath condensate is higher in obese patients with OSAS than in obese subjects without OSAS. Moreover, different mechanisms for determining leptin concentrations in the exhaled breath condensate and the blood are suggested. 相似文献
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Fábio S Lira José C Rosa Gustavo D Pimentel Victor AF Tarini Ricardo M Arida Flávio Faloppa Eduardo S Alves Cláudia O do Nascimento Lila M Oyama Marília Seelaender Marco T de Mello Ronaldo VT Santos 《Lipids in health and disease》2010,9(1):1-10
Introduction
Cytokines (IL-6, IL-10 and TNF-α) are increased after exhaustive exercise in the rat retroperitoneal (RPAT) and mesenteric adipose tissue (MEAT) pads. On the other hand, these cytokines show decreased expression in these depots in response to a chronic exercise protocol. However, the effect of exercise with overload combined with a short recovery period on pro- and anti-inflammatory cytokine expression is unknown. In the present study, we investigated the regulation of cytokine production in the adipose tissue of rats after an overtraining-inducing exercise protocol.Methods
Male Wistar rats were divided into four groups: Control (C), Trained (Tr), Overtrained (OT) and recovered overtrained (R). Cytokines (IL-6, TNF-α and IL-10) levels and Toll Like Receptor 4 (TLR4), Nuclear Factor kBp65 (NF-kBp65), Hormone Sensitive Lipase (HSL) and, Perilipin protein expression were assessed in the adipose tissue. Furthermore, we analysed plasma lipid profile, insulin, testosterone, corticosterone and endotoxin levels, and liver triacylglycerol, cytokine content, as well as apolipoprotein B (apoB) and TLR4 expression in the liver.Results
OT and R groups exhibited reduced performance accompanied by lower testosterone and increased corticosterone and endotoxin levels when compared with the control and trained groups. IL-6 and IL-10 protein levels were increased in the adipose tissue of the group allowed to recover, in comparison with all the other studied groups. TLR-4 and NF-kBp65 were increased in this same group when compared with both control and trained groups. The protein expression of HSL was increased and that of Perilipin, decreased in the adipose in R in relation to the control. In addition, we found increased liver and serum TAG, along with reduced apoB protein expression and IL-6 and IL-10 levels in the of R in relation to the control and trained groups.Conclusion
In conclusion, we have shown that increases in pro-inflammatory cytokines in the adipose tissue after an overtraining protocol may be mediated via TLR-4 and NF-kBp65 signalling, leading to an inflammatory state in this tissue. 相似文献110.