Bioassay-guided separation of an alpha-amylase inhibitor anthocyanin from Vaccinium arctostaphylos berries

Vaccinium arctostaphylos is a traditional medicinal plant in Iran used for the treatment of diabetes mellitus. In our search for antidiabetic compounds from natural sources, we found that the extract obtained from V. arctostaphylos berries showed an inhibitory effect on pancreatic alpha-amylase in vitro [IC50 = 1.91 (1.89-1.94) mg/mL]. The activity-guided purification of the extract led to the isolation of malvidin-3-O-beta-glucoside as an a-amylase inhibitor. The compound demonstrated a dose-dependent enzyme inihibitory activity [IC50 = 0.329 (0.316-0.342) mM].     

Conversion of cholic acid to methyl 3alpha-carbethoxy-12alpha-acetoxy-6-oxo-5beta-chol-7-en-24-oate

A new and efficient method for preparation of a 7-en-6-one derivative of cholic acid is described. Acetylation of the known methyl 3alpha-carbethoxy-12alpha-hydroxy-7-oxo-5beta-cholan-24-oate (3) at 12 position and reduction of its 7-oxo group yield the 12alpha-acetoxy-7alpha-hydroxy derivative 5. Dehydration of the 7alpha-hydroxy group in 5 followed by allylic oxidation provide methyl 3alpha-carbethoxy-12alpha-acetoxy-6-oxo-5beta-chol-7-en-24-oate (7) in good yield.     

Nasal tip sutures part II: the interplays

The achievement of consistently superior results in rhinoplasty is rendered difficult in part by a number of complex interplays between the anatomical structures of the nose and the techniques used for their alteration, such as tip sutures. The effects of sutures depend largely on the magnitude of suture tightening, the intrinsic forces on the cartilages, cartilage thickness, and the degree of soft-tissue undermining. The tip complex is perhaps the most intricate of the nasal structures, exhibiting subtle but evident responses to manipulations of the lower lateral cartilages. The three-dimensional effects of nine suture techniques that are frequently used in nasal tip surgical procedures are discussed and illustrated. (1) The medial crura suture approximates the medial crura and strengthens the support of the tip. The suture also has effects that are less conspicuous immediately. There is slight narrowing of the columella, caudal protrusion of the lobule, and minimal caudal rotation of the lateral crura. (2) The middle crura suture approximates the most anterior portion of the medial crura. There is greater strengthening of the tip and some approximation of the domes with this suture. (3) The interdomal suture approximates the domes and can equalize asymmetric domes. However, the entire tip may shift to the short side if there is a significant difference in the heights of the domes because of short lateral and medial crura. (4) Transdomal sutures narrow the domal arch while pulling the lateral crura medially. The net results are increased tip projection, alar rim concavity, and the potential need for an alar rim graft. In addition, depending on suture position, cephalic or caudal rotation of the lateral crura may be observed. (5) The lateral crura suture increases the concavity of the lateral crura, reduces the interdomal distance, and may retract the alar rims. Perhaps the most significant inadvertent results of this suture are caudal rotation of the tip and elongation of the nose. This is important because patients who undergo rhinoplasty would often benefit from cephalic, rather than caudal, rotation of the tip. (6) The medial crura-septal suture not only increases tip projection but also rotates the tip cephalically and retracts the columella. (7) The tip rotation suture shifts the tip cephalad while retracting the columella. (8) The medial crura footplate suture approximates the footplates, narrows the columella base, and improves undesirable nostril shape. (9) The lateral crura convexity control suture alters the degree of convexity of the lateral crura. The nuances of these sutures and their multiplanar effects on the nasal tip are discussed.     

Chemical composition of the fixed and volatile oils of Nigella sativa L. from Iran

The chemical composition of the extracted fixed oil (total fatty acid composition) and volatile oil of Nigella sativa L. seeds grown in Iran were determined by GC and GC/MS. Eight fatty acids (99.5%) and thirty-two compounds (86.7%) have been identified in the fixed and volatile oils, respectively. The main fatty acids of the fixed oil were linoleic acid (55.6%), oleic acid (23.4%), and palmitic acid (12.5%). The major compounds of the volatile oil were trans-anethole (38.3%), p-cymene (14.8%), limonene (4.3%), and carvone (4.0%).     

Inhibition of factor X and factor V activation by dermatan sulfate and a pentasaccharide with high affinity for antithrombin III in human plasma

There is evidence that by catalyzing thrombin inhibition, several glycosaminoglycans can inhibit the thrombin-mediated amplification reactions of coagulation and thereby delay prothrombin activation. The two amplification reactions can apparently be catalysed by endogenously generated factor Xa and thrombin. This study provides evidence which suggests that on a molar basis, an agent which can only catalyse thrombin inhibition is approximately 10 times more effective than an agent which can only catalyse factor Xa inhibition in their ability to inhibit intrinsic prothrombin activation. We determined the concentrations of each of heparin, dermatan sulfate and a pentasaccharide with high affinity for antithrombin III, to delay intrinsic prothrombin activation for at least 15s. Heparin catalyses both thrombin and factor Xa inhibition; dermatan sulfate catalyses only thrombin inhibition, while the pentasaccharide only catalyses factor Xa inhibition. Efficient prothrombin activation, which coincided with both factor X activation and factor V proteolysis, was first observed 45s after CaC12 was added to contact-activated plasma. Heparin (approximately 0.1 microM) prolonged by at least 30 s the time required for the activation of the three clotting factors to begin. The minimum concentrations of the pentasaccharide and dermatan sulfate to delay the activation of prothrombin, factors X and V were approximately 50 microM and approximately 5 microM, respectively. Thus, each anticoagulant could inhibit intrinsic prothrombin activation only when it inhibited activation of both factors X and V. A combination of approximately 5 microM pentasaccharide and approximately 0.05 microM dermatan sulfate similarly delayed the activation of all three clotting factors. Thus, while catalysis of thrombin inhibition is a more effective pathway than catalysis of factor Xa inhibition for delaying prothrombin activation, the simultaneous catalysis of thrombin and factor Xa inhibition can synergistically improve the ability of a sulfated polysaccharide to delay prothrombin activation.     

The anatomy of the greater occipital nerve: implications for the etiology of migraine headaches

An interest in pursuing new theories of the underlying etiology of migraine headaches has been sparked by previously published reports of an association between amelioration of migraine headache symptoms and corrugator resection during endoscopic brow lift. This theory has further been reinforced by recent publications documenting improvement in migraine headaches following injection of botulinum A toxin. There are thought to be four major "trigger points" along the course of several peripheral nerves that may cause migraine headaches. Among these peripheral nerves is the greater occipital nerve. For this reason, the authors have undertaken an anatomic study of this nerve to determine its usual course, potential anatomic variations, and possible points of potential entrapment or compression. The results of this anatomic study have enhanced further development of techniques designed to address these points of entrapment/compression and potentially lead to relief of migraine headaches caused by this mechanism. Twenty cadaver heads from patients with an unknown history of migraine headaches were dissected to trace the normal course of the greater occipital nerve from the semispinalis muscle penetration to the superior nuchal line. Standardized measurements were performed on 14 specimens to determine the location of the emergence of the nerve using the midline and occipital protuberance as landmarks. On the basis of this information, the location of emergence was determined to be at a point centered approximately 3 cm below the occipital protuberance and 1.5 cm lateral to the midline. This location can, in turn, be used to guide the practitioner performing chemodenervation of the semispinalis capitis muscle in an attempt to provide migraine symptom relief.     

Dynamic force spectroscopy of glycoprotein Ib-IX and von Willebrand factor

The first stage in hemostasis is the binding of the platelet membrane receptor glycoprotein (GP) Ib-IX complex to the A1 domain of von Willebrand factor in the subendothelium. A bleeding disorder associated with this interaction is platelet-type von Willebrand disease, which results from gain-of-function (GOF) mutations in amino acid residues 233 or 239 of the GP Ibalpha subunit of GP Ib-IX. Using optical tweezers and a quadrant photodetector, we investigated the binding of A1 to GOF and loss-of-function mutants of GP Ibalpha with mutations in the region containing the two known naturally occurring mutations. By dynamically measuring unbinding force profiles at loading rates ranging from 200-20,000 pN/s, we found that the bond strengths between A1 and GP Ibalpha GOF mutants (233, 235, 237, and 239) were significantly greater than the A1/wild-type GP Ib-IX bond at all loading rates examined (p < 0.05). In addition, mutants 231 and 232 exhibited significantly lower bond strengths with A1 than the wild-type receptors (p < 0.05). We computed unloaded dissociation rate constant (k(off)(0)) values for interactions involving mutant and wild-type GP Ib-IX receptors with A1 and found the A1/wild-type GP Ib-IX k(off)(0) value of 5.47 +/- 0.25 s(-1) to be significantly greater than the GOF k(off)(0) values and significantly less than the loss-of-function k(off)(0) values. Our data illustrate the importance of the bond kinetics associated with the VWF/GP Ib-IX interaction in hemostasis and also demonstrate the drastic changes in binding that can occur when only a single amino acid of GP Ibalpha is altered.     

SveDem,the Swedish Dementia Registry – A Tool for Improving the Quality of Diagnostics,Treatment and Care of Dementia Patients in Clinical Practice

BackgroundThe Swedish Dementia Registry (SveDem) was developed with the aim to improve the quality of diagnostic work-up, treatment and care of patients with dementia disorders in Sweden.MethodsSveDem is an internet based quality registry where several indicators can be followed over time. It includes information about the diagnostic work-up, medical treatment and community support (www.svedem.se). The patients are diagnosed and followed-up yearly in specialist units, primary care centres or in nursing homes.ResultsThe database was initiated in May 2007 and covers almost all of Sweden. There were 28 722 patients registered with a mean age of 79.3 years during 2007–2012. Each participating unit obtains continuous online statistics from its own registrations and they can be compared with regional and national data. A report from SveDem is published yearly to inform medical and care professionals as well as political and administrative decision-makers about the current quality of diagnostics, treatment and care of patients with dementia disorders in Sweden.ConclusionSveDem provides knowledge about current dementia care in Sweden and serves as a framework for ensuring the quality of diagnostics, treatment and care across the country. It also reflects changes in quality dementia care over time. Data from SveDem can be used to further develop the national guidelines for dementia and to generate new research hypotheses.     

PIA and rSesC Mixture Arisen Antibodies Could Inhibit the Biofilm-Formation in Staphylococcus aureus

Background:Staphylococcus aureus as a causative agent of hospital-acquired infections has been considered as the primary concern in biomaterial-related infections (BAIs).Methods:Following the purification of polysaccharide intercellular adhesion (PIA) as an efficient macromolecule in biofilm formation in the native condition, recombinant S. epidermidis surface-exposed rSesC protein, with the most homology to clumping factor A (ClfA) in S. aureus was cloned and expressed in a prokaryotic host as well. Fourier transform infrared spectrometry (FTIR) and Western blotting procedure analyzed purified PIA and protein, respectively. Then, the immune response was evaluated by measuring total IgG titers. Moreover, the capacity of Anti-biofilm forming activity of arisen antibodies to a biofilm-forming S. aureus strains was assessed by the semi-quantitative micro-plate procedure.Results:Data showed that the total IgGs were boosted in mice immunized sera. By performing an inhibition assay, the biofilm inhibitory effect of secreted antibodies to test strain was observed. Arisen antibodies against the mixture significantly were more potent than PIA and rSesC, when comparing individual antigens in a biofilm inhibition assay.Conclusion:immunization of mice with mentioned antigens especially a mixture of them, could eliminate the biofilm formation process in S. aureus. Hopefully, this study corresponds to the suggestion that the immunization of mice with PIA and rSesC candidate vaccines could protect against S. aureus infection.Key Words: PIA, Purification, Staphylococcus aureus, rSesC, Vaccine candidates