Introduction: Fibromyalgia is a syndrome characterized by chronic generalized pain in addition to different symptoms such as fatigue, sleep disturbances, stiffness, cognitive impairment, and psychological distress. Multidisciplinary treatment combining pharmacological and nonpharmacological therapies is advised.
Areas covered: Publications describing randomized controlled trials and long-term extension studies evaluating drug treatment for fibromyalgia were searched in PubMed and Scopus and included in this review.
Expert opinion: Different drugs are recommended for the treatment of fibromyalgia by different published guidelines, although only three of them have been approved for this indication by the US FDA, and none have been approved by the European Medicines Agency. According to the available evidence, pregabalin, duloxetine and milnacipran should be the drugs of choice for the treatment of this disease, followed by amitriptyline and cyclobenzaprine. Other drugs with at least one positive clinical trial include some selective serotonin reuptake inhibitors, moclobemide, pirlindole, gabapentin, tramadol, tropisetron, sodium oxybate and nabilone. None of the currently available drugs are fully effective against the whole spectrum of fibromyalgia symptoms, namely pain, fatigue, sleep disturbances and depression, among the most relevant symptoms. Combination therapy is an option that needs to be more thoroughly investigated in clinical trials. 相似文献
Renal cell carcinoma (RCC) is the most common renal malignancy in adults and exhibits highly intrinsic and acquired resistance to standard therapeutic strategies. We sought to determine the anti-cancer activity of hydroalcoholic extract of Nigella sativa seeds (NSE) and thymoquinone (TQ). Human renal cell carcinoma (ACHN) and fibroblast L929 cell lines were treated with NSE and TQ, and cytotoxicity was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay. Cell death pattern was determined by annexin V and propidium iodine (PI)-staining methods. Exposure to NSE, TQ and cisplatin significantly inhibited the growth of ACHN cells and showed significant increase of early apoptotic cells. Normal cells were more resistant to NSE and TQ-induced effects. The present study demonstrates that N. sativa and TQ exert anti-proliferative and pro-apoptotic effects on ACHN cells in a concentration and time-dependent manner, which suggests their potential to be used as a new therapeutic strategy for renal cancers. 相似文献
The aim of this study was to evaluate the use of different fixatives on the reliability of histopathological changes in a rabbit model of proliferative vitreoretinopathy (PVR). Twenty eyes from 10 rabbits were divided into four groups. The right eyes were used in two experimental groups (each n = 5), and the left, in two control groups (each n = 5). Using a newly developed scleral incision marker, an oblique scleral incision was standardized in the experimental groups, followed by intravitreal injection of 0.4 ml autologous blood and the left for wound repair for four weeks. Eyes were enucleated at four weeks. The groups differed in the type of used fixative solution (formaldehyde 4% vs. 1% buffered formaldehyde and 1.25% glutaraldehyde). The eyes were evaluated for the development of fibrosis, retinal detachment (RD), and processed for histopathology. Fibrous ingrowth of a variable degree was present in the experimental groups originating from the trauma site. Experimental eyes fixed with formaldehyde 4% had RD extension that was greater than that fixed in formaldehyde/glutaraldehyde mixture; however, the difference did not reach statistical significance (P = 0.15). This difference was not fully explained by the fibrosis which developed. In addition, in control groups, formaldehyde 4% induced a fixative-dependent retinal separation that was absent in eyes fixed with formaldehyde/glutaraldehyde mixture (P= 0.03). In conclusion, a mixture of buffered formaldehyde 1% and glutaraldehyde 1.25% combined with standardized scleral incision resulted in consistent pathological changes. A reliable PVR model is a condition sine qua non to evaluate antifibrotic treatment strategies. 相似文献
Background The impact of isolated diastolic dysfunction (IDD) and systolic dysfunction (SD) on health-related quality of life (HRQOL) is unknown. Methods and Results To evaluate HRQOL in patients with IDD and SD under treatment, information on outpatients aged 60-84 years was extracted from the records of 4,500 consecutive individuals who underwent echocardiographic examination at Sado General Hospital. The medical records of these patients were reviewed and a questionnaire, including the Medical Outcome Study Short Form 36, was mailed to 71 IDD and 99 SD patients; answers were obtained from 66 and 91 patients, respectively. The HRQOL of patients with cardiac dysfunction was impaired even when echocardiographic parameters improved with treatment. Patients with IDD showed an impairment of HRQOL similar to those with SD. Compared with males, female patients had a larger and more significant reduction in the physical and mental components of the HRQOL score. These scores correlated positively with exercise capacity in patients with IDD or SD. Conclusions Impaired HRQOL, in both its mental and physical components, is a serious problem for IDD and SD patients under treatment. Because exercise intolerance may underlie the reduced HRQOL, improving exercise capacity could be an important target for managing outpatients with heart failure. (Circ J 2008; 72: 1436 - 1442). 相似文献
BACKGROUND: The future burden of heart failure in Japan was projected to 2055 in order to prospectively estimate of the number of these patients. METHODS AND RESULTS: The statistics are based on prevalence data of left ventricular dysfunction (LVD) in Sado City using the Sado Heart Failure Study (2003) and population estimates from the Japanese National Institute of Population and Social Security Research Report (2006). The number of Japanese outpatients with LVD was 979,000 in 2005, and is predicted to increase gradually as the population ages, reaching 1.3 million by 2030. CONCLUSION: LVD is expected to precipitate a future epidemic of heart failure in Japan. 相似文献
To evaluate the effectiveness of exercise, ergonomic modification, and a combination of training exercise and ergonomic modification on the scores of pain in office workers with neck, shoulders, and lower back pain.
Methods
Participants (N = 142) in this randomized controlled trial were office workers aged 20–50 years old with neck, shoulders, and lower back pain. They were randomly assigned to either the ergonomic modification group, the exercise group, the combined exercise and ergonomic modification group, or the control group (no-treatment). The exercise training group performed a series of stretching exercises, while the ergonomic group received some modification in the working place. Outcome measures were assessed by the Cornell Musculoskeletal Disorders Questionnaire at baseline, after 2, 4, and 6 months of intervention.
Results
There was significant differences in pain scores for neck (MD ?10.55; 95%CI ?14.36 to ?6.74), right shoulder (MD ?12.17; 95%CI ?16.87 to ?7.47), left shoulder (MD ?11.1; 95%CI ?15.1 to ?7.09) and lower back (MD ?7.8; 95%CI ?11.08 to ?4.53) between the exercise and control groups. Also, significant differences were seen in pain scores for neck (MD ?9.99; 95%CI ?13.63 to ?6.36), right shoulder (MD ?11.12; 95%CI ?15.59 to ?6.65), left shoulder (MD ?10.67; 95%CI ?14.49 to ?6.85) and lower back (MD ?6.87; 95%CI ?10 to ?3.74) between the combined exercise and ergonomic modification and control groups. The significant improvement from month 4 to 6, was only seen in exercise group (p < 0.05).
Conclusion
To have a long term effective on MSDs, physical therapists and occupational therapists should use stretching exercises in their treatment programs rather than solely rely on ergonomic modification.
Cyclosporine (CSA) and non-steroidal anti-inflammatory drugs (NSAIDs) are co-prescribed for some arthritic conditions. We tested the hypothesis that this combined regimen elicits exaggerated nephrotoxicity in rats via the up-regulation of endothelin (ET) receptor signalling.
Experimental Approach
The effects of a 10 day treatment with CSA (20 mg·kg−1·day−1), indomethacin (5 mg·kg−1·day−1) or their combination on renal biochemical, inflammatory, oxidative and structural profiles were assessed. The roles of ETA receptor and COX-2 pathways in the interaction were evaluated.
Key Results
Oral treatment with CSA or indomethacin elevated serum urea and creatinine, caused renal tubular atrophy and interstitial fibrosis, increased renal TGF-β1, and reduced immunohistochemical expressions of ETA receptors and COX-2. CSA, but not indomethacin, increased renal ET-1, the lipid peroxidation product malondialdehyde (MDA) and GSH activity. Compared with individual treatments, simultaneous CSA/indomethacin exposure caused: (i) greater elevations in serum creatinine and renal MDA; (ii) loss of the compensatory increase in GSH; (iii) renal infiltration of inflammatory cells and worsening of fibrotic and necrotic profiles; and (iv) increased renal ET-1 and decreased ETA receptor and COX-2 expressions. Blockade of ETA receptors by atrasentan ameliorated the biochemical, structural, inflammatory and oxidative abnormalities caused by the CSA/indomethacin regimen. Furthermore, atrasentan partly reversed the CSA/indomethacin-evoked reductions in the expression of ETA receptor and COX-2 protein.
Conclusions and Implications
The exaggerated oxidative insult and associated dysregulation of the ETA receptor/COX-2/TGF-β1 signalling might account for the aggravated nephrotoxicity caused by the CSA/indomethacin regimen. The potential renoprotective effect of ETA receptor antagonism might be exploited therapeutically.Tables of Links
Open in a separate windowThese Tables list key protein targets and ligands in this article which are hyperlinked to corresponding entries in http://www.guidetopharmacology.org, the common portal for data from the IUPHAR/BPS Guide to PHARMACOLOGY (Pawson et al., 2014) and are permanently archived in the Concise Guide to PHARMACOLOGY 2013/14a,bAlexander et al., 2013a,b). 相似文献