Expression of anti-heterogenous nuclear ribonucleoprotein (anti-hnRNP) in limited systemic sclerosis patients: Relation to radiographic findings of the hand

Background

Systemic sclerosis (SSc) is an autoimmune connective tissue disease with vascular, fibrotic and immune changes of skin and some internal organs. Anti-heterogeneous nuclear ribonucleoproteins (anti-hnRNP) were found in SSc patients.

Bee venom acupuncture therapy ameliorates neuroinflammatory alterations in a pilocarpine-induced epilepticus model

Metabolic Brain Disease - Bee venom (BV) is applied in different traditional medicinal therapies and is used worldwide to prevent and treat many acute and chronic diseases. Epilepsy has various...     

Restless legs syndrome among Saudi end-stage renal disease patients on hemodialysis

Objectives:

To determine the prevalence of restless legs syndrome (RLS) in Saudi patients with end-stage renal disease (ESRD) on hemodialysis.

Methods:

A cross-sectional study was carried out in 3 hemodialysis centers in Jeddah, Saudi Arabia, between June 2012 and September 2013. All patients were individually interviewed and data was collected on the following demographic features, medical history, laboratory test, the International Restless Legs Syndrome Study Group questionnaire, Epworth Sleepiness Scale (ESS), and Berlin Questionnaire.

Results:

Three hundred and fifty-five patients were recruited. The prevalence of RLS among ESRD patients was 19.4%, with most patients having moderate to severe disease. The RLS was significantly associated with obstructive sleep apnea (p<0.0001) and excessive daytime sleepiness based on the ESS (p=0.009). The RLS showed no correlation with hemodialysis adequacy, chronicity, frequency per week, and hemodialysis duration per session; however, there was a weak negative relation between adequacy of hemodialysis and RLS severity. None of the comorbidities showed any association with RLS. The odds of developing RLS increased significantly with an increasing body mass index (p=0.001). Administration of aspirin (p=0.037) and anticoagulants (p=0.035) were also associated with increased risk of RLS.

Conclusion:

Restless legs syndrome is common in ESRD patients on hemodialysis, and it is an important source of sleep disruption. In addition to body mass index, Aspirin and anticoagulants may be important risk factors.Willis-Ekbom disease or restless legs syndrome (RLS) is a sleep-related, sensorimotor, neurological disorder that primarily affects the legs.1 When severe, the disorder can also affect the arms and other parts of the body. The RLS is characterized by sore sensations in the legs and accompanied by an urge to move them, typically in the evening and night. It is worse at rest and at least temporarily relieved by activity.1,2 The prevalence of RLS in the general population ranges from 5-15%.3 It can be idiopathic in nature or secondary to conditions such as diabetes mellitus, renal failure, iron deficiency anemia, multiple sclerosis, and pregnancy. The restlessness experienced by patients with RLS can cause problems such as insomnia, excessive daytime sleepiness, poor quality of life, and depression. In its severe forms, it can develop into a chronic and devastating disorder that may require long-term treatment. The clinical management of this condition is to treat the possible causes as well as to use different drugs for symptomatic relief. However, there is no definitive cure for this condition. Patients on regular hemodialysis (HD) for the management of end-stage renal disease (ESRD) are prone to various neurological disorders, including RLS. The prevalence of RLS among HD patients is approximately 20-30%.4,5 In a Serbian study, Nikić et al6 evaluated 166 patients on HD using the International Restless Legs Syndrome Study Group (IRLSSG) criteria and found that the prevalence of RLS was 22.7%. Goffredo Filho et al7 also reported the frequency of RLS to be 14.8% among 176 Brazilian patients. With regard to our region, Salman8 reported that the prevalence of RLS was 20.3% in 123 Syrian patients on chronic HD. Finally, Al-Jahdali et al9 conducted the single local study on 227 ESRD patients on chronic hemodialysis and found that the prevalence of RLS was 50.2%. This rate was much higher than that reported previously in majority of similar studies, particularly in light of the fact that the reported percentage of RLS in the Saudi population was only 5.2%.10 In this study, our aim was to determine the prevalence of RLS among a sample of Saudi patients with ESRD maintained on regular HD, and to compare the obtained value with that previously reported. Additionally, we explored the association between the adequacy of hemodialysis and severity of RLS symptoms.     

Remote loading of curcumin-in-modified β-cyclodextrins into liposomes using a transmembrane pH gradient

Curcumin (CRM) is a natural polyphenol with antioxidative, anti-inflammatory, and anticancer therapeutic properties. However, CRM therapeutic potential is limited by low water solubility and bioavailability. Intraliposomal remote loading describes the retention of drugs in liposome cores in response to transmembrane pH gradient. The current study describes for the first time the remote loading of CRM into liposomes using secondary (E-βCD) and tertiary (D-βCD) amino-modified β-cyclodextrins (βCDs) as carriers and solubilizers. βCDs were chemically modified to prepare the ionizable weak base functional group followed by forming a guest-host complex of CRM in the modified βCDs hydrophobic cavities via a solvent evaporation encapsulation technique. These complexes were then actively loaded into preformed liposomes, composed of DPPC/cholesterol (65/35 molar ratio) via pH gradient. The formation of CRM-βCDs inclusion complexes was characterized using UV-Vis spectroscopy, thermal analysis, and NMR spectroscopy. The complex stoichiometric ratio was determined to be 1 : 1 of CRM-βCDs based on Job''s plot which was also confirmed by the modified Benesi–Hildebrand equation with increasing probability of forming the 1 : 2 ratio of CRM-βCDs. The apparent formation constants (K_f) of 51.6, 100.9 and 55.4 mM⁻² were determined for CRM-βCD, CRM-E-βCD, and CRM-D-βCD complexes, respectively. Liposome size, charge and polydispersity index indicate the presence of a homogeneous population before and after active loading. The encapsulation efficiencies of CRM-βCD complexes into pH gradient preformed liposomes were 16.5, 51.1, and 41.7 for CRM-βCD, CRM-E-βCD, and CRM-D-βCD, respectively, showing more than 5 fold increase compared to normal liposomes. The current study provides a novel remote loading approach utilizing chemically modified cyclodextrins to incorporate hydrophobic drugs into liposomes.

The current study provides a novel remote loading approach utilizing chemically modified cyclodextrins to incorporate hydrophobic drugs into liposomes.     

Production of certified reference materials for the sports doping control of the REV‐ERB agonist SR9009

Two human metabolites of the REV‐ERB agonist SR9009, identified by researchers with an interest in sports doping control, have been synthesized and assessed for purity. The synthesis employed was a modification of published procedures for the parent SR9009, careful attention to the purification of intermediates and the final product ensuring materials of the highest purity were available for certification. For each candidate material impurities of related structure were identified and quantified as a relative mass fraction using high performance liquid chromatography–ultraviolet (HPLC–UV) detection and proton nuclear magnetic resonance (¹H NMR) spectroscopy. The quantification of water, occluded solvent, and inorganic residue was assessed using Karl Fischer, ¹H NMR, and thermogravimetric analysis, thereby completing the assessment of all impurities typically characterized by the mass balance approach. Summation and subtraction from 1000 mg/g afforded the mass fraction of the main component, the associated uncertainty ensuring certified reference material status can be applied to the resulting pure substance calibration standards. The availability of these standards to the sports doping control community will facilitate delivery of metrological traceability to the SI unit for mass (kg) to routine testing results and aid method development for the detection and quantification of SR9009 abuse.     

Natural product diversity from the endophytic fungi of the genus Aspergillus

The endophytic fungus Aspergillus is considered as an enormous source of chemical leads with promising biological activities. Different Aspergillus species have proved their ability to produce plenty of secondary metabolites including butenolides, alkaloids, terpenoids, cytochalasins, phenalenones, ρ-terphenyls, xanthones, sterols, diphenyl ether and anthraquinone derivatives with diverse biological activities, such as anti-cancer, antifungal, anti-bacterial, anti-viral, anti-inflammatory, antitrypanosomal and antileishmanial activities. From January 2015 until December 2019, three hundred and sixty-one secondary metabolites were reported from different endophytic Aspergillus species. This review discusses the isolated secondary metabolites from different endophytic Aspergillus species reported from January 2015 to December 2019 along with their reported biological activities and structural aspects whenever applicable.

The endophytic fungus Aspergillus is the precious source of chemical biodiversity.     

Major complications related to epidural analgesia in children: a 15-year audit of 3,152 epidurals

Background

Complications associated with epidural analgesia in children have a reported incidence of 40-90 in 10,000 epidurals. We sought to determine the incidence of major complications with the use of continuous epidural analgesia that occurred in our centre over the past 15 years and to describe the nature of these complications.

Methods

The Acute Pain Service database at a tertiary care academic pediatric hospital was reviewed retrospectively over a 15-year period. Data were categorized according to patient age (neonate, infant, child one through eight years, and child > eight years), mode of insertion of the epidural (caudal, transsacral, lumbar, thoracic), complication type, and complication severity.

Results

Over the 15-year period, 3,152 epidurals were performed. The use of caudal-thoracic epidurals in neonates and infants has increased since 2007. Twenty-four major complications were identified (incidence, 7.6 in 1,000 epidurals). The rate of complications in neonates was 4.2% compared with 1.4% in infants, 0.5% in children aged one through eight years, and 0.8% in children over eight years of age. The two most common complications were local skin infection and drug error.

Conclusions

Our incidence of major complications and our finding that complications were more common in neonates and infants are both consistent with previously published data. The two most common types of complications are potentially preventable.