Efficacy of artichoke leaf extract in non‐alcoholic fatty liver disease: A pilot double‐blind randomized controlled trial

Non‐alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide and is potentially treatable, though there are few therapeutic agents available. Artichoke leaf extract (ALE) has shown potential as a hepatoprotective agent. This study sought to determine if ALE had therapeutic utility in patients with established NAFLD. In this randomized double‐blind placebo‐controlled parallel‐group trial, 100 subjects with ultrasound‐diagnosed NAFLD were randomized to either ALE 600 mg daily or placebo for a 2‐month period. NAFLD response was assessed by liver ultrasound and serological markers including the aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio and AST to platelet ratio index (APRI) score. Ninety patients completed the study (49 ALE and 41 placebo) with no side effects reported. ALE treatment compared with placebo: Doppler sonography showed increased hepatic vein flow (p < .001), reduced portal vein diameter (p < .001) and liver size (p < .001), reduction in serum ALT (p < .001) and AST (p < .001) levels, improvement in AST/ALT ratio and APRI scores (p < .01), and reduction in total bilirubin. ALE supplementation reduced total cholesterol, low‐density lipoprotein cholesterol, high‐density lipoprotein cholesterol, non‐high‐density lipoprotein cholesterol, and triglyceride concentrations (p = .01). This study has shown beneficial effects of ALE supplementation on both ultrasound liver parameters and liver serum parameters (ALT, AST, APRI ratio, and total bilirubin) in patients with NAFLD.     

Null Allele Frequencies at HLA-G Locus in Iranian Healthy Subjects

Background: HLA-G gene contains 15 alleles including a null allele, HLA-G*0105N. Previous studies have shown that HLA-G*0105N does not encode the complete HLA-G1 or HLA-G5 isoforms but encodes a functional HLA-G protein with the ability to in-hibit NK cell cytolysis. Thus, although the biological functions of HLA-G1 and HLA-G5 proteins are abrogated, other isoforms such as HLA-G2 can replace their roles. Stud-ies on the null allele of HLA-G gene could be useful in understanding the genetic vari-ants of HLA-G alleles in ethnic groups. Objective: The goal of this research was to de-termine the frequency of HLA-G*0105N null allele in Iranian healthy subjects. Meth-ods: The frequency of HLA-G*0105N null allele was evaluated in Iranian healthy sub-jects by PCR-RFLP method. Genomic DNA was isolated from the whole blood of 100 randomly selected, healthy, unrelated Iranian individuals using salting-out technique followed by PCR amplification of the exon 3 of HLA-G gene. PCR products were di-gested with PpUM-1 and the resulted fragments were analyzed using gel electrophore-sis. Results: In this study the restriction enzyme digestion confirmed homozygous HLA-G*0105N null allele for 9 % of the population. Furthermore obtained results indi-cated that the total frequency of HLA-G*0105N null allele was 20 % in the studied population of Iran. Conclusion: The final data analysis showed that the total frequency of this allele in Iranian people was higher than other ethnic groups that have been stud-ied so far.     

Prooxidant-anti-oxidant balance is not associated with extent of coronary artery disease

Objective

We have measured the pro-oxidant–antioxidant-balance (PAB) levels in patients with defined coronary artery disease (CAD) and compared them with concentrations in healthy subjects.

Design and methods

Based on angiography results, 400 patients with stable CAD were divided into CAD− and CAD+, this being further subcategorized into groups with single-, double- and triple-vessel disease (VD).

Results

The mean PAB values in the healthy subjects, was significantly lower than for other groups (P < 0.001). In CAD− patients, PAB levels were 123.2 ± 43.9, which was not statistically different compared to groups with SVD, 2VD and 3VD (P > 0.05). In the CAD+ group, PAB values in 1VD, 2VD and 3VD were not significantly different among patients with SVD, 2VD and 3VD (P > 0.05).

Conclusions

In conclusion, we found higher levels of oxidative stress in CAD+ patients compared to healthy subjects. The oxidation level was not related to measures of the extent of CAD such as number of stenosed vessels.     

Morphological alterations of T24 cells on flat and nanotubular TiO2 surfaces

Aim

To investigate morphological alterations of malignant cancer cells (T24) of urothelial origin seeded on flat titanium (Ti) and nanotubular titanium dioxide (TiO₂) nanostructures.

Methods

Using anodization method, TiO₂ surfaces composed of vertically aligned nanotubes of 50-100 nm diameters were produced. The flat Ti surface was used as a reference. The alteration in the morphology of cancer cells was evaluated using scanning electron microscopy (SEM). A computational model, based on the theory of membrane elasticity, was constructed to shed light on the biophysical mechanisms responsible for the observed changes in the contact area of adhesion.

Results

Large diameter TiO₂ nanotubes exhibited a significantly smaller contact area of adhesion (P < 0.0001) and had more membrane protrusions (eg, microvilli and intercellular membrane nanotubes) than on flat Ti surface. Numerical membrane dynamics simulations revealed that the low adhesion energy per unit area would hinder the cell spreading on the large diameter TiO₂ nanotubular surface, thus explaining the small contact area.

Conclusion

The reduction in the cell contact area in the case of large diameter TiO₂ nanotube surface, which does not enable formation of the large enough number of the focal adhesion points, prevents spreading of urothelial cells.The material and topographical characteristics of the contact surface affect the functional activity of cells (1-7). Titanium is the most widely used material in numerous medical applications, because it is non-toxic. The titanium surface has recently been modified by a self-assembled layer of vertically oriented titanium oxide (TiO₂) nanotubes with diameters between 15 nm and 100 nm (8-10). It was revealed that cell adhesion, spreading, growth, and differentiation was maximally induced on 15 nm nanotubes, but hindered on 100 nm nanotubes, which facilitated cell death (8,9). These results suggest that magnitude of TiO₂ nanotube diameter has an important role in cell adhesion and cell growth, and that the mechanics of the formation of focal adhesions is similar between different types of cells. The aim of the present study is to analyze effects of flat titanium and nanotubular TiO₂ surfaces on the morphology of malignant cancer cells (T24) of urothelial origin.Using anodization method, vertically aligned TiO₂ nanotubular surfaces were produced (Figure 1). The produced nanotubes had a large diameter (50-100 nm). The T24 cells grown on the nanotubular surface had a smaller top view diameter and more membrane protrusions than the counterpart on the flat titanium surface. A computational model was constructed to shed light on the biophysical mechanism underlying the observed morphologic changes. The underlying hypothesis is that the low density of TiO₂ nanotube edges could not facilitate the cell adhesion, ie, the formation of large enough number of focal adhesion points. Mathematically, the density of negative charges is predicted to be greatest at sharp edges (7), which would then facilitate the mediated electrostatic interactions between the TiO₂ nanotube surface and membrane proteins at the focal contact. Using numerical simulations of membrane dynamics, it is revealed that low adhesion of the membrane to the large diameter nanotubular surface is not sufficient to counterbalance the loss of entropic energy during the clustering of proteins at a focal contact, and consequently, the increased membrane bending energy does not favor intensive spread of cancer cells on the large diameter TiO₂ nanotube surface underneath.Open in a separate windowFigure 1Scanning electron microscopy images of surface layers of self-assembled vertically aligned TiO₂ nanotubes synthesized by anodization method. Ethylene glycol solution with 0.3 wt % NH₄F and 1% volume water was used in preparation. High-resolution scanning electron microscopy FEG-SEM 7600F from JEOL was used. Images were taken at 100000× magnitude using low accelerating voltage of 2kV. The internal TiO₂ tube diameter was around 50-60 nm (A-D) and 100 nm (E-F) while the length could be up to 10 micrometers (B).     

Validity and reliability of a Persian translation of the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS)

Cognitive dysfunction is common in multiple sclerosis (MS) and validated batteries are limited in languages other than English. We aimed to translate, cross-culturally adapt, validate, and assess reliability of Minimal Assessment of Cognitive Function in MS (MACFIMS) in Persian. The MACFIMS is a well-constructed battery in the MS literature. The battery was adapted to Persian in accordance with available guidelines. A total of 158 MS patients and 90 controls underwent neuropsychological assessment. For reliability assessment the battery was re-administered in a subset of 41 patients after a short interval using alternate forms to mitigate practice effects (approximately 10 days). Patients performed significantly worse than controls in all cognitive tests, supporting discriminant validity of our adapted battery. Approximately half of patients (46.2%) showed cognitive impairment as defined by the impairment in two or more tests. The Symbol Digit Modalities Test was the most robust test by ROC analysis. All tests showed acceptable to good level of reliability. This is the first validation of gold-standard cognitive testing in Persian. The Persian MACFIMS shows nearly the same psychometrics as its English counterpart.     

Clinical evaluation of 222 Iranian patients with halitosis

The primary objectives of the study were to investigate the levels of volatile sulfur compounds (VSCs) in Iranian patients and to find the most prevalent class of halitosis among them. The secondary objective was to study the measures employed by the patients to reduce halitosis. 46.4% of the 222 patients were female (average 32.1 years) and 53.6% were male (average 32.1 years). Contrary to other reports, males were dominant in this study. All the subjects were evaluated through oral examination, gas chromatographic analysis, organoleptic assessment and mouth cleaning and rinsing test (MCART). Finally, each patient was classified according to current classification. The patients were also asked about the measures employed by them to reduce halitosis. The data were statistically analysed using SPSS software. Gas chromatographic analysis revealed that the median values for H(2)S, CH(3)SH and (CH(3))(2)S levels were 214 ppb, 64 ppb and 2 ppb, respectively. Average values of H(2)S, CH(3)SH and (CH(3))(2)S were 358.7 ppb, 143.0 ppb and 19.5 ppb, respectively. A correlation was demonstrated between organoleptic scores and the concentration of only H(2)S, CH(3)SH and the total of three gases. In 62.2% of the subjects, no oral pathologic condition was found, but tongue coating was observed. The patients were in only class I (genuine halitosis) and class II (pseudo-halitosis) halitosis. None of them was diagnosed as halitophobia. The percentages of classes I and II were 98.6% and 1.4%, respectively. The percentages of sub-classes of class I halitosis in total subjects were as follows: 60.8% physiologic halitosis, 37.8% oral pathologic halitosis and 0% extraoral pathologic halitosis. The mean value of organoleptic score for physiologic halitosis was 4.0 and those for oral pathologic halitosis and pseudo-halitosis were 4.3 and 1.6, respectively. MCART was a useful tool to distinguish oral halitosis from extraoral halitosis. Levels of VSCs were not as high as those measured in other countries. Although in most cases VSCs were a contributing factor to halitosis, VSCs levels were not useful diagnostic criteria for the minority of the patients. The most prevalent class and sub-class of halitosis in the patients were genuine halitosis and physiologic halitosis. Measures employed by the patients to reduce halitosis were mostly related to the oral cavity.     

Investigation of the Efficacy of Adjunctive Therapy with Bioavailability‐Boosted Curcuminoids in Major Depressive Disorder

Current medications have limited efficacy in controlling the symptoms of major depressive disorder (MDD), and are associated with several adverse events on long‐term use. Curcuminoids are extremely safe and multifunctional phytopharmaceuticals that have been shown to alleviate depressive symptoms in a variety of experimental models. The present study aimed to investigate the efficacy of curcuminoids as an add‐on to standard antidepressants in patients with MDD. One hundred and eleven subjects were assigned to standard antidepressive therapy plus curcuminoids–piperine combination (1000–10 mg/day; n = 61) or standard antidepressive therapy alone (n = 50) for a period of 6 weeks. Efficacy measures were changes in the psychological status on the basis of the Hospital Anxiety and Depression Scale (HADS) and Beck Depression Inventory II (BDI‐II). The BDI‐II and HADS total and subscale scores were reduced by the end of trial in both study groups. There were significantly greater reductions in total HADS score and subscales of anxiety and depression in the curcuminoids versus control group (p < 0.001). Likewise, reductions in BDI‐II total score and scores of somatic and cognitive subscales were found to be greater in the curcuminoids compared with control group (p < 0.001). Co‐administration of curcuminoids with piperine may be used as a safe and effective add‐on to standard antidepressants in patients with MDD. Copyright © 2014 John Wiley & Sons, Ltd.