Optimization of amino acid-stabilized erythropoietin parenteral formula: In vitro and in vivo assessment

The aim of this study was to optimize the formulation of erythropoietin (EPO) using amino acids instead of human serum albumin (HSA) and to evaluate its in vivo stability in order to avoid the risk of viral contamination and antigenicity. Different EPO formulas were developed in such a way was to allow studying the effects of amino acids and surfactants on the EPO stability profile. The main techniques applied for EPO analysis were ELISA, Bradford method, and SDS gel electrophoresis. The in vivo stability was evaluated in a Balb-c mouse animal model. The results showed that the presence of surfactant was very useful in preventing the initial adsorption of EPO on the walls of vials and in minimizing protein aggregation. Amino acid combinations, glycine with glutamic acid, provided maximum stability. Formulation F4 (containing glycine, glutamic acid and Tween 20) showed minimum aggregation and degradation and in vivo activity equivalent to commercially available HSA-stabilized EPO (Eprex®)

Efficacy of memantine in the treatment of fibromyalgia: A double-blind, randomised, controlled trial with 6-month follow-up.

Fibromyalgia (FM) is a prevalent and disabling chronic disease. Recent studies have found elevated levels of glutamate in several brain regions, leading to hypotheses about the usefulness of glutamate-blocking drugs such as memantine in the treatment of FM. The aim of this study was to evaluate the efficacy of memantine in the treatment of pain and other clinical variables (global function, clinical impression, depression, anxiety, quality of life) in FM patients. A double-blind, parallel randomised controlled trial was developed. A total of 63 patients diagnosed with FM were recruited from primary health care centres in Zaragoza, Spain. Memantine was administered at doses of 20mg/d after 1 month of titration. Assessments were carried out at baseline, posttreatment, and 3- and 6-month follow-up. Compared with a placebo group, memantine significantly decreased ratings on a pain visual analogue scale (Cohen's d=1.43 at 6 months) and pain measured with a sphygmomanometer (d=1.05). All other secondary outcomes except anxiety also improved, with moderate-to-large effect sizes at 6 months. Compared with placebo, the absolute risk reduction obtained with memantine was 16.13% (95% confidence interval=2.0% to 32.6%), and the number needed to treat was 6.2 (95% confidence interval=3 to 47). Tolerance was good, with dizziness (8 patients) and headache (4 patients) being the most frequent side effects of memantine. Although additional studies with larger sample sizes and longer follow-up times are needed, this study provides preliminary evidence of the utility of memantine for the treatment of FM

Helicobacter Pylori Infection in Children with Type 1 Diabetes Mellitus

Objective: To evaluate H. pylori infection and virulent strain in diabetic children. Patients: In this study 53 type 1 diabetics and 53 of normal volunteers were included. Methods: All studied children were subjected to assessment of glycosylated hemoglobin (HbA1), Anti H. pylori antibodies (IgA, IgG, IgM), Anti-cytotoxin associated gene A antibodies (Anti Cag A IgG). Results: Anti H. pylori antibodies IgA, IgG, total antibodies and anti Cag A IgG were significantly higher in diabetics. Diabetic patients with positive anti Cag A IgG had a lower age of onset of diabetes, higher age of patients, body mass index (BMI) and HbA1. Conclusion: High prevalence of infection with the virulent strain of H. pylori among diabetic children with older age, large BMI, high HbA1 and younger age of onset of disease. The screening for the virulent strain in diabetic patients with poor metabolic control is mandatory. Control of diabetes is essential to present the infection with H. pylori

Effects of Different Parameters of Diode Laser on Acceleration of Orthodontic Tooth Movement and Its Effect on Relapse: An Experimental Animal Study

AIM: Recent studies have demonstrated that low-level laser therapy (LLLT) can accelerate orthodontic tooth movement. However, there is still controversy about the optimum parameters that can cause acceleration. The present study was designed to examine two different doses of LLLT in the acceleration of orthodontic tooth movement and their effect on relapse. METHODS: An orthodontic appliance was designed to induce tooth movement on lower incisors of rabbits. The in-al-as diode laser was used to radiate different groups of rabbits according to a specific protocol. The amount of tooth movement was measured for 21 days, and then the orthodontic appliance was removed, and the relapse was measured till day 28. RESULTS: The amount of tooth movement was significantly greater in the group with irradiation of low dose in comparison with the high dose group and the control group. The relapse was greatest in the group of low dose irradiation and least in the control group. CONCLUSION: The findings suggest that LLLT with a low dose accelerate the orthodontic tooth movement while LLLT with a high dose was not able to have the same effect. LLLT had a reverse effect on relapse tendency; an increase in the relapse tendency was seen with low dose irradiation

Sub-micron moulding topological mass transport regimes in angled vortex fluidic flow

Shear stress in dynamic thin films, as in vortex fluidics, can be harnessed for generating non-equilibrium conditions, but the nature of the fluid flow is not understood. A rapidly rotating inclined tube in the vortex fluidic device (VFD) imparts shear stress (mechanical energy) into a thin film of liquid, depending on the physical characteristics of the liquid and rotational speed,ω, tilt angle,θ, and diameter of the tube. Through understanding that the fluid exhibits resonance behaviours from the confining boundaries of the glass surface and the meniscus that determines the liquid film thickness, we have established specific topological mass transport regimes. These topologies have been established through materials processing, as spinning top flow normal to the surface of the tube, double-helical flow across the thin film, and spicular flow, a transitional region where both effects contribute. The manifestation of mass transport patterns within the film have been observed by monitoring the mixing time, temperature profile, and film thickness against increasing rotational speed,ω. In addition, these flow patterns have unique signatures that enable the morphology of nanomaterials processed in the VFD to be predicted, for example in reversible scrolling and crumbling graphene oxide sheets. Shear-stress induced recrystallisation, crystallisation and polymerisation, at different rotational speeds, provide moulds of high-shear topologies, as ‘positive’ and ‘negative’ spicular flow behaviour. ‘Molecular drilling’ of holes in a thin film of polysulfone demonstrate spatial arrangement of double-helices. The grand sum of the different behavioural regimes is a general fluid flow model that accounts for all processing in the VFD at an optimal tilt angle of 45°, and provides a new concept in the fabrication of novel nanomaterials and controlling the organisation of matter

Case report: Utilizing diffusion-weighted MRI on a patient with chronic low back pain treated with spinal cord stimulation

Diffusion-weighted magnetic resonance imaging (dwMRI) has increasingly demonstrated greater utility in analyzing neuronal microstructure. In patients with chronic low back pain (cLBP), using dwMRI to observe neuronal microstructure can lead to non-invasive biomarkers which could provide clinicians with an objective quantitative prognostic tool. In this case report, we investigated dwMRI for the development of non-invasive biomarkers by conducting a region-based analysis of a 55-year-old male patient with failed back surgery syndrome (FBSS) treated with spinal cord stimulation (SCS). We hypothesized that dwMRI could safely generate quantitative data reflecting cerebral microstructural alterations driven by neuromodulation. Neuroimaging was performed at 6- and 12- months post-SCS implantation. The quantitative maps generated included diffusion tensor imaging (DTI) parameters; fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) computed from whole brain tractography. To examine specific areas of the brain, 44 regions of interest (ROIs), collectively representing the pain NeuroMatrix, were extracted and registered to the patient's diffusion space. Average diffusion indices were calculated from the ROIs at both 6- and 12- months. Regions with >10% relative change in at least 3 of the 4 maps were reported. Using this selection criterion, 8 ROIs demonstrated over 10% relative changes. These ROIs were mainly located in the insular gyri. In addition to the quantitative data, a series of questionnaires were administered during the 6- and 12-month visits to assess pain intensity, functional disability, and quality of life. Overall improvements were observed in these components, with the Pain Catastrophizing Scale (PCS) displaying the greatest change. Lastly, we demonstrated the safety of dwMRI for a patient with SCS. In summary, the results from the case report prompt further investigation in applying dwMRI in a larger cohort to better correlate the influence of SCS with brain microstructural alterations, supporting the utility of dwMRI to generate non-invasive biomarkers for prognostication

Effect of high parity on occurrence of anemia in pregnancy: a cohort study

<p>Abstract</p> <p>Background</p> <p>Studies that explore the controversial association between parity and anaemia-in-pregnancy (AIP) were often hampered by not distinguishing incident cases caused by pregnancy from prevalent cases complicated by pregnancy. The authors' aim in conducting this study was to overcome this methodological concern.</p> <p>Methods</p> <p>A retrospective cohort study was conducted in Oman on 1939 pregnancies among 479 parous female participants with available pregnancy records in a community trial. We collected information from participants, the community trial, and health records of each pregnancy. Throughout the follow-up period, we enumerated 684 AIP cases of which 289 (42.2%) were incident cases. High parity (HP, ≥ 5 pregnancies) accounted for 48.7% of total pregnancies. Two sets of regression analyses were conducted: the first restricted to incident cases only, and the second inclusive of all cases. The relation with parity as a dichotomy and as multiple categories was examined for each set; multi-level logistic regression (MLLR) was employed to produce adjusted models.</p> <p>Results</p> <p>In the fully adjusted MLLR models that were restricted to incident cases, women with HP pregnancies had a higher risk of AIP compared to those who had had fewer pregnancies (Risk Ratio, RR = 2.92; 95% CI 2.02, 4.59); the AIP risk increased in a dose-response fashion over multiple categories of parity. In the fully adjusted MLLR models that included all cases, the association disappeared (RR = 1.11; 95% CI 0.91, 1.18) and the dose-response pattern flattened.</p> <p>Conclusions</p> <p>This study shows the importance of specifying which cases of AIP are incident and provides supportive evidence for a causal relation between parity and occurrence of incidental AIP.</p

Correlational analysis and predictive validity of psychological constructs related with pain in fibromyalgia

<p>Abstract</p> <p>Background</p> <p>Fibromyalgia (FM) is a prevalent and disabling disorder characterized by a history of widespread pain for at least three months. Pain is considered a complex experience in which affective and cognitive aspects are crucial for prognosis. The aim of this study is to assess the importance of pain-related psychological constructs on function and pain in patients with FM.</p> <p>Methods</p> <p>Design</p> <p>Multicentric, naturalistic, one-year follow-up study.</p> <p><it>Setting and study sample</it>. Patients will be recruited from primary care health centres in the region of Aragon, Spain. Patients considered for inclusion are those aged 18-65 years, able to understand Spanish, who fulfil criteria for primary FM according to the American College of Rheumatology, with no previous psychological treatment.</p> <p>Measurements</p> <p>The variables measured will be the following: main variables (pain assessed with a visual analogue scale and with sphygmomanometer and general function assessed with Fibromyalgia Impact Questionnaire, and), psychological constructs (pain catastrophizing, pain acceptance, mental defeat, psychological inflexibility, perceived injustice, mindfulness, and positive and negative affect), and secondary variables (sociodemographic variables, anxiety and depression assessed with Hospital Anxiety and Depression Scale, and psychiatric interview assessed with MINI). Assessments will be carried at baseline and at one-year follow-up.</p> <p>Main outcome</p> <p>Pain Visual Analogue Scale.</p> <p>Analysis</p> <p>The existence of differences in socio-demographic, main outcome and other variables regarding pain-related psychological constructs will be analysed using Chi Square test for qualitative variables, or Student <it>t </it>test or variance analysis, respectively, for variables fulfilling the normality hypothesis. To assess the predictive value of pain-related psychological construct on main outcome variables at one-year follow-up, use will be made of a logistic regression analysis adjusted for socio-demographic and clinical variables. A Spearman Rho non-parametric correlation matrix will be developed to determine possible overlapping between pain-related psychological constructs.</p> <p>Discussion</p> <p>In recent years, the relevance of cognitive and affective aspects for the treatment of chronic pain, not only in FM but also in other chronic pain diseases, has been widely acknowledged. However, the relative importance of these psychological constructs, the relationship and possible overlapping between them, or the exact meaning of them in pain are not enough known.</p

Insula-specific responses induced by dental pain: a proton magnetic resonance spectroscopy study

OBJECTIVES: To evaluate whether induced dental pain leads to quantitative changes in brain metabolites within the left insular cortex after stimulation of the right maxillary canine and to examine whether these metabolic changes and the subjective pain intensity perception correlate. METHODS: Ten male volunteers were included in the pain group and compared with a control group of 10 other healthy volunteers. The pain group received a total of 87-92 electrically induced pain stimuli over 15 min to the right maxillary canine tooth. Contemporaneously, they evaluated the subjective pain intensity of every stimulus using an analogue scale. Neurotransmitter changes within the left insular cortex were evaluated by MR spectroscopy. RESULTS: Significant metabolic changes in glutamine (+55.1%), glutamine/glutamate (+16.4%) and myo-inositol (-9.7%) were documented during pain stimulation. Furthermore, there was a significant negative correlation between the subjective pain intensity perception and the metabolic levels of Glx, Gln, glutamate and N-acetyl aspartate. CONCLUSION: The insular cortex is a metabolically active region in the processing of acute dental pain. Induced dental pain leads to quantitative changes in brain metabolites within the left insular cortex resulting in significant alterations in metabolites. Negative correlation between subjective pain intensity rating and specific metabolites could be observed