An update on pharmacotherapy for the treatment of fibromyalgia

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.     

Cytotoxic and apoptogenic properties of Nigella sativa and thymoquinone,its constituent,in human renal cell carcinoma are comparable with cisplatin

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.     

Effect of different fixative solutions on eyes with experimental proliferative vitreoretinopathy

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.     

Health-related quality of life of outpatients with systolic and isolated diastolic dysfunction

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).     

Impending epidemic: future projection of heart failure in Japan to the year 2055.

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.     

Modification of graphene oxide film properties using KrF laser irradiation

Modification of various properties of graphene oxide (GO) films on SiO₂/Si substrate under KrF laser radiation was extensively studied. X-ray diffraction, X-ray photoelectron spectroscopy, Raman spectroscopy and the electrical resistance measurements were employed to correlate the effects of laser irradiation on structural, chemical and electrical properties of GO films under different laser fluences. Raman spectroscopy shows reduced graphene oxide patterns with increased I_2D/I_G ratios in irradiated samples. X-ray photoelectron spectroscopy shows a high ratio of carbon to oxygen atoms in the reduced graphene oxide (rGO) films compared to the pristine GO films. X-ray diffraction patterns display a significant drop in the diffraction peak intensity after laser irradiation. Finally, the electrical resistance of irradiated GO films reduced by about four orders of magnitudes compared to the unirradiated GO films. Simultaneously, reduction and patterning of GO films display promising fabrication technique that can be useful for many graphene-based devices.

Modification of various properties of graphene oxide (GO) films on SiO₂/Si substrate under KrF laser radiation was extensively studied.     

Sequential hydrophile and lipophile solubilization as an efficient method for decellularization of porcine aortic valve leaflets: Structure,mechanical property and biocompatibility study

Antigenicity of xenogeneic tissues is the major obstacle to increased use of these materials in clinical medicine. Residual xenoantigens in decellularized tissue elicit the immune response after implantation, causing graft failure. With this in mind, the potential use is proposed of three protein solubilization‐based protocols for porcine aortic valve leaflets decellularization. It was demonstrated that hydrophile solubilization alone achieved incomplete decellularization; lipophile solubilization alone (LSA) completely removed all cells and two most critical xenoantigens – galactose‐α(1,3)‐galactose (α‐Gal) and major histocompatibility complex I (MHC I) – but caused severe alterations of the structure and mechanical properties; sequential hydrophile and lipophile solubilization (SHLS) resulted in a complete removal of cells, α‐Gal and MHC I, and good preservation of the structure and mechanical properties. In contrast, a previously reported method using Triton X‐100, sodium deoxycholate and IGEPAL CA‐630 resulted in a complete removal of all cells and MHC I, but with remaining α‐Gal epitope. LSA‐ and SHLS‐treated leaflets showed significantly reduced leucocyte activation (polymorphonuclear elastase) upon interaction with human blood in vitro. When implanted subdermally in rats for 6 weeks, LSA‐ or SHLS‐treated leaflets were presented with more biocompatible implants and all four decellularized leaflets were highly resistant to calcification. These findings illustrate that the SHLS protocol could be considered as a promising decellularization method for the decellularization of xenogeneic tissues in tissue engineering and regenerative medicine. Copyright © 2016 John Wiley & Sons, Ltd.     

Effects of stretching exercise training and ergonomic modifications on musculoskeletal discomforts of office workers: a randomized controlled trial

Objective

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.

Adenosine triphosphate/adenosine guided pulmonary vein isolation does not improve the outcomes of ablation: a meta-analysis of randomized controlled trials

Background: Successful pulmonary vein isolation (PVI) is the most reliable predictor of success after ablation in patients with atrial fibrillation (AF). Adenosine triphosphate (ATP) unmasks the dormant conduction and can be used to improve the effectiveness of PVI. The impact of ATP guided PVI on clinical outcomes is discordant in various randomized controlled trials (RCTs).

Objectives: To delineate the incremental benefit of ATP during PVI in patients with AF through a meta-analysis.

Methods and results: Database searches through January 2017 identified 5 RCTs (enrolling 2839 patients) comparing ATP guided PVI versus standard PVI (non-ATP). Four trials exclusively studied paroxysmal AF while one trial included both paroxysmal and non-paroxysmal AF patients. Baseline characteristics, dose of adenosine and ablation strategies were clearly identified among all the trials. The risk ratio (RR) for AF episodes lasting >30 s after 3-month blanking period was calculated with random effects meta-analysis and showed no difference at a median follow up of 12 months [RR: 1.02, 95 % Confidence interval (CI): 0.85 to 1.25; p = 0.82]. Similarly, the number of repeat ablation was similar in both groups [RR: 1.02, 95 % CI: 0.63, 1.56; p = 0.98].

Conclusions: ATP guided PVI does not decrease the recurrence of AF or the need for repeat ablation at 12 months.