Introduction: HIV-1-infected smokers are at risk of oxidative damage to neuronal cells in the central nervous system by both HIV-1 and cigarette smoke. Since neurons have a weak antioxidant defense system, they mostly depend on glial cells, particularly astrocytes, for protection against oxidative damage and neurotoxicity. Astrocytes augment the neuronal antioxidant system by supplying cysteine-containing products for glutathione synthesis, antioxidant enzymes such as SOD and catalase, glucose for antioxidant regeneration via the pentose-phosphate pathway, and by recycling of ascorbic acid.
Areas covered: The transport of antioxidants and energy substrates from astrocytes to neurons could possibly occur via extracellular nanovesicles called exosomes. This review highlights the neuroprotective potential of exosomes derived from astrocytes against smoking-induced oxidative stress, HIV-1 replication, and subsequent neurotoxicity observed in HIV-1-positive smokers.
Expert opinion: During stress conditions, the antioxidants released from astrocytes either via extracellular fluid or exosomes to neurons may not be sufficient to provide neuroprotection. Therefore, we put forward a novel strategy to combat oxidative stress in the central nervous system, using synthetically developed exosomes loaded with antioxidants such as glutathione and the anti-aging protein Klotho. 相似文献
BACKGROUND: The purpose of the present study was to evaluate the efficacy of a guided bone regeneration (GBR) procedure prior to implant placement and the long-term outcome of the inserted implants. METHODS: Prior to dental implant placement, GBR procedure was performed on 14 patients (mean age 48 years) using a synthetic hydroxyapatite (HA) spacer under a collagen membrane. After a mean healing period of 8 months, bone biopsies were obtained during the placement of 14 implants. The specimens were processed for histology without demineralization in order to assess bone quality and quantity of the regenerated bone. RESULTS: Both the bone density and the resorption degree of HA particles were relatively varied between samples. The different phenotypes of osteoclasts and multinucleated giant cells and the individual host response could partially explain the unpredictable results in terms of bone remodeling and biomaterial resorption. However, the presence of HA particles in the regenerated bone had no influence on the osseointegration of implants presenting a success rate of 86% after a 7-year observation period. CONCLUSIONS: These results confirm the possibility of regenerating bone by means of bioabsorbable materials, assuring at the same time the long-term success for implants inserted in regenerated sites. 相似文献
Warfarin is the most widely prescribed vitamin K antagonist and in the United States and Europe more than 10 million people are currently in long-term oral anticoagulant treatment. This study aims to retrospectively validate a dynamic statistical model providing dosage suggestions to patients in warfarin treatment.
Materials and methods
The model was validated on a cohort of 553 patients with a mean TTR of 83%. Patients in the cohort were self-monitoring and managed by a highly specialised anticoagulation clinic. The predictive model essentially consists of three parts handling INR history, warfarin dosage and biological noise, which allows for prediction of future INR values and optimal warfarin dose to stay on INR target. Further, the model is based on parameters initially being set to population values and gradually individualised during monitoring of patients.
Primary outcome
Time in therapeutic range was used as surrogate quality measure of the treatment, and model-suggested dosage of warfarin was used to assess the accuracy of the model performance.
Results
The accuracy of the model predictions measured as median absolute error was 0.53 mg/day (interquartile range from 0.25 to 1.0). The model performance was evaluated by the difference between observed and predicted warfarin intake in the preceding week of an INR measurement. In more than 70% of the cases where INR measurements were outside the therapeutic range, the model suggested a more reasonable dose than the observed intake.
Conclusion
Applying the proposed dosing algorithm can potentially further increase the time in INR target range beyond 83%. 相似文献
In 1995, by reverse pharmacology approach, used here for the first time in the history of pharmacology, nociceptin/orphanin FQ (N/OFQ) has been discovered as the endogenous ligand of a preidentified receptor named opioid receptor like 1. Subsequent studies showed that N/OFQ and its receptor (N/OFQergic system) are widely distributed in central and peripheral nervous systems as well as in peripheral organs of human and animals, and represent a system that is involved in a very large range of biological functions such as pain perception, intestinal motility and secretion, immune modulation, stress. From the time of its discovery to now, a high number of NOP agonists and antagonists have been synthesized and tested in various pathologies. Nevertheless, none of the molecules targeting N/OFQergic system have currently succeeded in going through clinical trials concerning gut pathologies, indicating that further studies are required. The work from Dr. Fichna et al., published in the present issue of Neurogastroenterology and Motility, adds another brick in the wall of understanding the role of N/OFQergic system in IBS‐D pathology by the pharmacological evaluation of a new NOP receptor agonist, SCH 221510, in animal models of intestinal alterations (diarrhea and visceral hyperalgesia). Interestingly, authors report clinical data confirming the involvement of N/OFQergic system in IBS‐D patients and, consequently, suggest this system as a valuable therapeutic target for IBS‐D pathology. This minireview aims to give a brief summary of experimental and clinical studies focusing on the N/OFQergic system as pharmacological target for the therapeutic treatment of intestinal pathologies such as IBS and IBD. 相似文献
Statistical testing of clinical trial data leads to acceptance of a hypothesis if a test of the opposite (null) hypothesis (H0) fails to reach a critical probability value. The usual aim is to demonstrate that a new treatment is superior to a comparator, whence H0 is that the two treatments are the same. By contrast, in studies designed to show that a new treatment is equivalent to an existing therapy, the same principle is satisfied by an amended null hypothesis, that the treatments differ by more than a defined amount. This reversal entails subtle but important logical and practical problems which affect particularly the calculation of sample size. The choice of the limits used to define equivalence is critical to the calculation of sample size in a manner not previously discussed, and in the interpretation of data in relation to the probability of Type I and Type II errors. Investigators, regulatory bodies and institutional ethics committees must ensure that the range of values chosen to indicate equivalence is clinically appropriate and be aware of the effect of this decision on possible errors in accepting or rejecting H0. 相似文献
Transarterial chemoembolization (TACE) is considered a therapeutic option. It is mostly used in hepatocellular carcinoma or liver colorectal, neuroendocrine or melanoma metastases. Although it is considered a safe procedure, TACE presents complications, such as acute cholecystitis, which is the most common. Other procedure-related complications include pulmonary embolism, hepatic abscess, bile duct injury, gastric mucosa injury and, less frequently, acute pancreatitis. The aim of this study is to review the complications following TACE for liver tumors.
Methods
We performed a retrospective study including all the TACE procedures performed in a single center during the period between January 2013 and December 2016.
Results
Out of the 196 patients with liver tumors who had undergone 322 TACE, 258 (80%) were male and 64 (20%) were female. Mean patient age was 66.5 years. Major complications after chemoembolization included: decompensation with edema/ascites (6 patients), acute cholecystitis (4), acute pancreatitis (3), liver rupture (1), liver abscess (1) and renal failure (1). Postembolization syndrome appeared in 71 (20%) patients. On multivariate analysis, it was observed that concomitant cardiovascular disease (OR: 4.5; 95% CI: 1.2-17; P = .025) is a risk factor for the development of complications.
Conclusions
TACE is a safe and effective procedure for liver tumor treatment. The majority of the complications are rare and present a low incidence of mortality. 相似文献