Phytotherapy of Opioid Dependence and Withdrawal Syndrome: A Review

Development of tolerance and dependence is a major problem associated with opioid treatment. Withdrawal syndrome is common between medical and illicit users of these agents. Phytomedicine has shown promise in the treatment of this complicated psychosomatic condition. In this study, the effects of plant extracts and active components on morphine dependence and withdrawal syndrome are discussed. Proper keywords were used to search through PubMed, Google Scholar, and SciVerse, as well as two local scientific databases, www.iranmedex.com and www.SID.com . All relevant results (original articles, meeting abstracts, patents, etc.) published from 2000 to 2013 were chosen for final review. A total of 35 plant species were studied on this subject. Plants from Lamiaceae, Ranunculaceae, and Apiaceae families were especially effective. A few studies were carried out on human subjects and the rest in animal models. Opioid dependence and withdrawal syndrome remain an intimidating challenge. Nonetheless, plants and their derivatives are suitable sources for their treatment. Although there are several plants shown to be effective in animal models, few clinical studies are available. Copyright © 2013 John Wiley & Sons, Ltd.     

Biomedical applications of yeast- a patent view,part one: yeasts as workhorses for the production of therapeutics and vaccines

Introduction: Yeasts, as Eukaryotes, offer unique features for ease of growth and genetic manipulation possibilities, making it an exceptional microbial host.

Areas covered: This review provides general and patent-oriented insights into production of biopharmaceuticals by yeasts. Patents, wherever possible, were correlated to the original or review articles. The review describes applications of major GRAS (generally regarded as safe) yeasts for the production of therapeutic proteins and subunit vaccines; additionally, immunomodulatory properties of yeast cell wall components were reviewed for use of whole yeast cells as a new vaccine platform. The second part of the review will discuss yeast- humanization strategies and innovative applications.

Expert opinion: Biomedical applications of yeasts were initiated by utilization of Saccharomyces cerevisiae, for production of leavened (fermented) products, and advanced to serve to produce biopharmaceuticals. Higher biomass production and expression/secretion yields, more similarity of glycosylation patterns to mammals and possibility of host-improvement strategies through application of synthetic biology might enhance selection of Pichia pastoris (instead of S. cerevisiae) as a host for production of biopharmaceutical in future. Immunomodulatory properties of yeast cell wall β-glucans and possibility of intracellular expression of heterologous pathogen/tumor antigens in yeast cells have expanded their application as a new platform, ‘Whole Yeast Vaccines’.     

Adeno-associated virus as a gene therapy vector: strategies to neutralize the neutralizing antibodies

Clinical and Experimental Medicine - Adeno-associated virus (AAV)-derived vectors are currently the most common type of viral vectors used in gene therapy clinical trials. The presence of...     

A systematic review on organochlorine and organophosphorus pesticides content in water resources

Water resources pollution by uncontrolled usage of pesticides is one of the most critical health and environmental problems. However, to protect the ecosystems and to design strategy plans, it is essential to obtain information on type and amount of pesticide residues in water resources. The present study presents an overview of two important pesticides: organo-chlorine and organo-phosphorus in world-water resources. Based on literature review, most of studies have been conducted in Asian countries, and the amount that have been reported in water resources in these countries was more than the permissible level. The high-level of δ-HCH (Lindane) pesticides in groundwater with concentration ～82.21?μg/L was detected in China. In addition, the maximum measured concentration of Diazinon was detected in surface water in Iran with the value of ～768.91?μg/L. The overview of the studies shows widespread presence of pesticides in water resources, and it was found that surface waters were more contaminated by pesticides.     

Xylose phosphorylation functions as a molecular switch to regulate proteoglycan biosynthesis

Most eukaryotic cells elaborate several proteoglycans critical for transmitting biochemical signals into and between cells. However, the regulation of proteoglycan biosynthesis is not completely understood. We show that the atypical secretory kinase family with sequence similarity 20, member B (Fam20B) phosphorylates the initiating xylose residue in the proteoglycan tetrasaccharide linkage region, and that this event functions as a molecular switch to regulate subsequent glycosaminoglycan assembly. Proteoglycans from FAM20B knockout cells contain a truncated tetrasaccharide linkage region consisting of a disaccharide capped with sialic acid (Siaα2–3Galβ1–4Xylβ1) that cannot be further elongated. We also show that the activity of galactosyl transferase II (GalT-II, B3GalT6), a key enzyme in the biosynthesis of the tetrasaccharide linkage region, is dramatically increased by Fam20B-dependent xylose phosphorylation. Inactivating mutations in the GALT-II gene (B3GALT6) associated with Ehlers-Danlos syndrome cause proteoglycan maturation defects similar to FAM20B deletion. Collectively, our findings suggest that GalT-II function is impaired by loss of Fam20B-dependent xylose phosphorylation and reveal a previously unappreciated mechanism for regulation of proteoglycan biosynthesis.The human genome encodes more than 500 protein kinases, most of which phosphorylate protein substrates in the nucleus and cytosol and play important roles in cell signaling (1, 2). Kinases that specifically phosphorylate glycans have only rarely been reported and our knowledge of their physiological functions remains in its infancy (3–5). Fam20B (family with sequence similarity 20, member B) is a recently identified atypical secretory pathway kinase (6, 7). Genetic studies have shown that deletion of Fam20B in mice results in embryonic lethality at embryonic day 13.5 (E13.5), whereas loss-of-function mutations in the fam20b gene in Danio rerio cause aberrant cartilage formation and severe skeletal defects that are linked to abnormal proteoglycan (PG) biosynthesis (8, 9).PGs are a special family of glycoconjugates consisting of one or more glycosaminoglycan (GAG) side chains covalently linked to specific Ser residues within a protein core via a common linkage tetrasaccharide [glucuronic acid-β1–3-galactose-β1–3-galactose-β1–4-xylose-β1 (GlcAβ1–3Galβ1–3Galβ1–4Xylβ1)] as illustrated in Fig. 1A (10). Mature GAGs are sulfated linear polysaccharides that are further classified as heparan sulfate (HS) or chondroitin/dermatan sulfate (CS), depending on the specific composition of elongated sugar repeats (11). PGs are expressed on the cell surface and in the extracellular matrix of all animal cells and tissues, playing critical roles in cell–cell and cell–matrix interactions and signaling, largely through the attached GAGs (12). The cellular machinery required for PG biosynthesis is conserved over a wide range of eukaryotic organisms and altered PG biosynthesis is associated with numerous human disease states (13–17). Thus, understanding how this process is regulated will be important. Loss of Fam20B appears to decrease the amount of cellular GAG chains and causes profound defects in embryonic development and skeletal formation (6, 8, 9). Fam20B has been reported to have xylose kinase activity against α-thrombomodulin, a glycoprotein bearing the tetrasaccharide linkage fragment. However, the specific molecular mechanism by which Fam20B-dependent xylose phosphorylation regulates PG synthesis is not clear.Open in a separate windowFig. 1.Xylosyl kinase Fam20B phosphorylates authentic proteoglycans. (A) Schematic representation of proteoglycan core proteins, glycosaminoglycan side chains, structure of the linkage tetrasaccharide, and biosynthetic enzymes involved. (B) Gel electrophoresis and Coomassie staining of recombinant Fam20B protein purified from insect cell conditioned medium. (C) Time-dependent incorporation of ³²P from [γ-³²P]ATP into decorin by Fam20B or Fam20B D309A (D/A) treated with or without chondroitinase ABC (Chon-ABC). Reaction products were analyzed by gel electrophoresis and autoradiography (autorad). (D) Lentiviral ShRNA mediated knockdown of Fam20B in MRC-5 cells and [³²P]orthophosphate metabolic labeling. Fam20B knockdown efficiency was determined by immunoblotting of endogeneous Fam20B. The level of decorin phosphorylation in the control (Sh-ctrl) and Fam20B knockdown (ShRNA) cells were visualized by ³²P autoradiography after decorin immunoprecipitation and gel electrophoresis. (E) Structure of synthetic Tetra-Ben as a model substrate for Fam20B. (F) Fam20B kinase reaction velocity versus [Mn²⁺]ATP concentration using Tetra-Ben as a substrate. (G) Fam20B kinase reaction velocities versus concentration of Tetra-Ben, Gal-Xyl-Ben, and Xyl-Ben artificial substrates. The reaction products for F and G were purified using SepPak C18 cartridges and the incorporated ³²P radioactivity was quantified by scintillation counting. Data points were fitted by nonlinear regression of the Michaelis–Menten equation. Error bars are SD of three independent experiments.Here we provide evidence that Fam20B is a xylose kinase that phosphorylates the initiator xylose residue within the tetrasaccharide linkage region of a wide array of O-linked PGs. We show that Fam20B requires a minimal Gal-Xyl disaccharide motif for activity, and loss of Fam20B-dependent xylose phosphorylation results in premature termination of the tetrasaccharide linkage and impaired glycosaminoglycan assembly. Our findings suggest that phosphorylation of xylose within the linkage region by Fam20B dramatically increases the activity of galactosyltransferase II (GalT-II), an enzyme necessary for completion of the linkage region and efficient glycosaminoglycan assembly. Cells lacking either Fam20B or GalT-II are unable to complete the assembly of the linkage region and exhibit only short sugar stubs within their proteoglycans. Our findings reveal a previously unappreciated mechanism for regulation of proteoglycan assembly and offer insight into the molecular basis of diseases associated with aberrant proteoglycan maturation.     

Development of a liquid-phase microextraction based on the freezing of a deep eutectic solvent followed by HPLC-UV for sensitive determination of common pesticides in environmental water samples

In this research, a new extraction method based on liquid-phase microextraction and the freezing of deep eutectic solvent (LPME-FDES) has been developed for the determination of common pesticides in water samples prior to their analysis by high performance liquid chromatography-ultraviolet detection (HPLC-UV). In this method, a green solvent consisting of 1-octyl-3-methylimidazolium chloride and 1-undecanol was used as an extraction solvent, yielding the advantages of material stability, low density, and a suitable freezing point near room temperature. Under the optimum conditions, enrichment factors and extraction recoveries are in the range of 150–180 and 75–90%, respectively. The calibration graphs are linear in the range of 0.2–500 μg L⁻¹ and limit of detections (LODs) are in the range of 0.05–0.50 μg L⁻¹. Relative standard deviation (RSD) values for intra-day and inter-day of the method based on seven replicate measurements of 200 μg L⁻¹ of diazinon and endosulfan, 100 μg L⁻¹ of phosalone, 50.0 μg L⁻¹ of atrazine, desethylatrazine and deisopropylatrazine in water were in the range of 1.3–2.5% and 2.2–3.6%, respectively. The relative recoveries of well, tap and river water samples which have been spiked with different levels of target pesticides are 97–106, 90–108 and 95–107%, respectively. The extraction methodology is simple, rapid, cheap and green since small amounts of non-toxic solvents are necessary.

In this research, a new extraction method based on liquid-phase microextraction and the freezing of deep eutectic solvent has been developed for the determination of pesticides in water prior to their analysis by HPLC-UV.     

Comparison Between Two Techniques for the Treatment of Mandibular Subcondylar Fractures: Closed Treatment Technique and Transoral Endoscopic-Assisted Open Reduction

Purpose

The endoscopic-assisted technique for the treatment of subcondylar fractures has been used successfully and its acceptance develops as more surgeons gain experience. We present the short term results of this technique in a randomized prospective clinical trial.

Methods and Materials

A total of 40 patients with mandibular subcondylar fracture were included in our study in two groups randomly. Patients of first group were treated by closed treatment technique and patients of second group by transoral endoscopic-assisted open reduction. All patients were followed for minimum of 12 weeks and occlusion, Mandibular Anterior Opening (MAO), mandibular deviation, and posterior ramal height were assessed.

Results

In the endoscopic group the MAO was significantly greater and mandibular deviation was lesser at 2nd and 4th week of follow up. Posterior ramal height showed significant increase in the endoscopic group rather than closed treatment group.

Conclusion

The transoral endoscopic-assisted technique is a reliable and successful technique to address subcondylar fractures. The patients who were treated by this technique showed better results in the fields of mandibular function and patient satisfaction and comfort, although it is time consuming and needs expensive instruments.