(E)‐2‐benzylidene‐4‐phenyl‐1,3‐diselenole has antioxidant and hepatoprotective properties against oxidative damage induced by 2‐nitropropane in rats

The in vitro effect of (E)‐2‐benzylidene‐4‐phenyl‐1,3‐diselenole (BPD) was evaluated through iron/EDTA‐induced thiobarbituric acid reactive species (TBARS) and reactive species (RS) determinations as well as of the scavenging 2,2′‐diphenyl‐1‐picrylhydrazyl (DPPH) radical quantification. BPD at the concentrations of 10 and 50 μΜ decreased RS and TBARS levels, respectively. The antioxidant activity was not related to the scavenging DPPH radical mechanism. A second objective of this study was to investigate the hepatoprotective action of BPD, administered by oral route, against oxidative damage induced by 2‐nitropropane (2‐NP) (100 mg/kg of body weight) in liver of rats. At the dose of 50 mg/kg, BPD protected against the increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities induced by 2‐NP. BPD (10 and 50 mg/kg) protected against the increase in TBARS levels and alkaline phosphatase (ALP) activity. Sections of liver from 2‐NP‐exposed rats presented intense infiltration of inflammatory cells and loss of cellular architecture. BPD (10 and 50 mg/kg) attenuated 2‐NP‐induced hepatic histological alterations. The inhibition of δ‐aminolevulinic dehydratase (δ‐ALA‐D), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S‐transferase (GST) activities and the decreased GSH levels caused by 2‐NP were protected by BPD (50 mg/kg). Catalase activity and ascorbic acid levels were not altered by 2‐NP. These results demonstrated the antioxidant and hepatoprotective effects of BPD in liver of rats.     

Human platelet antigen polymorphisms (HPA‐1, ‐2, ‐3, ‐4, ‐5 and ‐15) in major ethnic groups of Pakistan

Objectives: Gene frequencies of human platelet antigens (HPA) determine the magnitude of platelet immunological disorders like neonatal alloimmune thrombocytopenia, platelet refractoriness and ease of availability of particular HPA‐typed platelet donors in a given community. Background: However, the pattern of HPA in Pakistani population is not known. Aim: The aim of present study was to determine the gene frequencies of HPA (HPA‐1 to ‐5 and ‐15) in individuals belonging to major ethnic groups and castes of Pakistani population. Materials and Methods: HPA genotyping was done in 593 individuals belonging to all ethnic groups of Pakistan, by polymerase chain reaction‐sequence specific primers with detection on polyacrylamide electrophoresis. Results: The gene frequencies of the ‘a’ and ‘b’ alleles of HPA‐1 to ‐5 and ‐15 in Pakistanis were as follows: HPA‐1a/b, 0·885/0·115; HPA‐2a/b, 0·92/0·08; HPA‐3a/b, 0·69/0·31; HPA‐4a/b, 1/0; HPA‐5a/b, 0·9/0·1; HPA‐15a/b, 0·59/0·41. Except for significant difference regarding gene frequency of HPA‐3 between Pathans and Sindhis, there was no significant difference of HPA‐1 to ‐5 and ‐15 between major ethnic groups of Pakistan. The estimated mismatch probability regarding platelet antigens 1–5 and 15 in Pakistanis, after transfusion of random donor platelets, is from 14 to 37%. The expected incidence of neonatal alloimmune thrombocytopenia due to anti‐HPA‐1a in Pakistani pregnant females is < 1 of 1000 pregnancies and 8–12 of 1000 in case of anti‐HPA‐5b. Homozygosity of HPA‐1b, ‐2b and ‐5b genotypes ranged from 1 to 2% in the Pakistani population, whereas homozygosity of HPA‐3b and ‐15b was 11 and 18%. Conclusions: There is a need to establish donor registries typed for HPA in the transfusion centres of the country.     

Sonographic appearance of proliferative fasciitis‐‐‐A case report

Proliferative fasciitis is a benign entity involving the subcutaneous tissues and fascias, characterized by the proliferation of fibroblast‐like spindle cells and ganglion‐like cells. However, proliferative fasciitis may be easily confused with sarcoma clinically and pathologically, because it appears as a rapidly growing painful mass and has histologic features such as high cellularity, bizarre morphologic patterns, mitotic figures, and diffuse infiltrative proliferation. Imaging findings of proliferative fasciitis have been very rarely reported. We report the sonographic findings in a case of proliferative fasciitis in a 43‐year‐old woman with histopathological correlation. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45 :445–449, 2017     

Additive manufacturing of poly[(R)‐3‐hydroxybutyrate‐co‐(R)‐3‐hydroxyhexanoate] scaffolds for engineered bone development

A wide range of poly(hydroxyalkanoate)s (PHAs), a class of biodegradable polyesters produced by various bacteria grown under unbalanced conditions, have been proposed for the fabrication of tissue‐engineering scaffolds. In this study, the manufacture of poly[(R)‐3‐hydroxybutyrate‐co‐(R)‐3‐hydroxyhexanoate] (or PHBHHx) scaffolds, by means of an additive manufacturing technique based on a computer‐controlled wet‐spinning system, was investigated. By optimizing the processing parameters, three‐dimensional scaffolds with different internal architectures were fabricated, based on a layer‐by‐layer approach. The resulting scaffolds were characterized by scanning electron microscopy, which showed good control over the fibre alignment and a fully interconnected porous network, with porosity in the range 79–88%, fibre diameter 47–76 µm and pore size 123–789 µm. Moreover, the resulting fibres presented an internal porosity connected to the external fibre surface as a consequence of the phase‐inversion process governing the solidification of the polymer solution. Scaffold compressive modulus and yield stress and strain could be varied in a certain range by changing the architectural parameters. Cell‐culture experiments employing the MC3T3‐E1 murine pre‐osteoblast cell line showed good cell proliferation after 21 days of culture. The PHBHHx scaffolds demonstrated promising results in terms of cell differentiation towards an osteoblast phenotype. Copyright © 2014 John Wiley & Sons, Ltd.     

The effects of intramolecular H‐bond formation on the stability constant and water exchange rate of the Gd(III)‐diethylenetriamine‐N′‐(3‐amino‐1,1‐propylenephosphonic)‐N,N,N″,N″‐tetraacetate complex

The binding interaction of metal chelates to biological macromolecules, though driven by properly devoted recognition synthons, may cause dramatic changes in some property associated with the coordination cage such as the thermodynamic stability or the exchange rate of the metal coordinated water. Such changes are due to electrostatic and H‐bonding interactions involving atoms of the coordination cage and atoms of the biological molecule at the binding site. To mimic this type of H‐bonding interactions, lanthanide(III) complexes with a DTPA–monophosphonate ligand bearing a propylamino moiety (H₆NP–DTPA) were synthesized. Their thermodynamic stabilities and the exchange lifetime of the coordinated water molecule (for the Gd‐complex) were compared with those of the analog complexes with DTPA and the parent DTPA–monophosphonate derivative (H₆P–DTPA). It was found that the intramolecular H‐bond between the ε‐amino group and the phosphonate moiety in NP–DTPA complexes causes displacements of electric charges in their coordination cage that are markedly pH dependent. In turn, this affects the characteristic properties of the coordination cage. In particular it results in a marked elongation of the exchange lifetime of the coordinated water molecule. Copyright © 2007 John Wiley & Sons, Ltd.     

2‐(Trimethylammonium)ethyl (R)‐3‐methoxy‐3‐oxo‐2‐stearamidopropyl phosphate promotes megakaryocytic differentiation of myeloid leukaemia cells and primary human CD34+ haematopoietic stem cells

In this study we showed that 2‐(t rimethylammonium)e thyl (R)‐3‐m ethoxy‐3‐o xo‐2‐s tearamidopropyl pho sphate [(R)‐TEMOSPho], a derivative of an organic chemical identified from a natural product library, promotes highly efficient differentiation of megakaryocytes. Specifically, (R)‐TEMOSPho induces cell cycle arrest, cell size increase and polyploidization from K562 and HEL cells, which are used extensively to model megakaryocytic differentiation. In addition, megakaryocyte‐specific cell surface markers showed a dramatic increase in expression in response to (R)‐TEMOSPho treatment. Importantly, we demonstrated that such megakaryocytic differentiation can also be induced from primary human CD34⁺ haematopoietic stem cells. Activation of the PI3K–AKT pathway and, to a lesser extent, the MEK–ERK pathway appears to be required for this process, as blocking with specific inhibitors interferes with the differentiation of K562 cells. A subset of (R)‐TEMOSPho‐treated K562 cells undergoes spontaneous apoptosis and produces platelets that are apparently functional, as they bind to fibrinogen, express P‐selectin and aggregate in response to SFLLRN and AYPGFK, the activating peptides for the PAR1 and PAR4 receptors, respectively. Taken together, these results indicate that (R)‐TEMOSPho will be useful for dissecting the molecular mechanisms of megakaryocytic differentiation, and that this class of compounds represents potential therapeutic reagents for thrombocytopenia. Copyright © 2012 John Wiley & Sons, Ltd.     

Antibacterial and β‐Lactamase Inhibitory Activity of Monocyclic β‐Lactams

Due to the widespread emergence of resistant bacterial strains, an urgent need for the development of new antibacterial agents with novel modes of action has emerged. The discovery of naturally occurring monocyclic β‐lactams in the late 1970s, mainly active against aerobic Gram‐negative bacteria, has introduced a new approach in the design and development of novel antibacterial β‐lactam agents. The main goal was the derivatization of the azetidin‐2‐one core in order to improve their antibacterial potency, broaden their spectrum of activity, and enhance their β‐lactamase stability. In that respect, our review covers the updates in the field of monocyclic β‐lactam antibiotics during the last three decades, taking into account an extensive collection of references. An overview of the relationships between the structural features of these monocyclic β‐lactams, classified according to their N‐substituent, and the associated antibacterial or β‐lactamase inhibitory activities is provided. The different paragraphs disclose a number of well‐established classes of compounds, such as monobactams, monosulfactams, monocarbams, monophosphams, nocardicins, as well as other known representative classes. Moreover, this review draws attention to some less common but, nevertheless, possibly important types of monocyclic β‐lactams and concludes by highlighting the recent developments on siderophore‐conjugated classes of monocyclic β‐lactams.     

Endothelium‐dependent and endothelium‐independent effects of 1‐nitro‐2‐propylbenzene on rat aorta

A group of nitro compounds contains a benzene ring in a short aliphatic chain with the NO₂ group, property that supposedly favors its vasodilator profile. In this study, we evaluated in isolated rat aorta the effects of 1‐nitro‐2‐propylbenzene (NPB), a nitro compound containing the NO₂ in the aromatic ring. In aorta precontracted with KCl, NPB (1‐3000 μm ) induced full endothelium‐independent relaxation. In endothelium‐intact preparations, phenylephrine‐induced contractions were fully relaxed by NPB, effect unaltered by N(ω)‐nitro‐L‐arginine methyl ester (L‐NAME) or 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ). In the concentration range of 30–300 μm , NPB slightly but significantly potentiated the phenylephrine‐induced contraction. Such potentiation was unaltered by the thromboxane‐prostanoid receptor antagonist seratrodast, but was abolished by endothelium removal or by preincubation of endothelium‐intact preparations with L‐NAME, ODQ or by ruthenium red and HC‐030031, blockers of subtype 1 of ankyrin transient receptor potential (TRPA₁) channels. Verapamil exacerbated the potentiating effect of NPB. The potentiating effect was undetectable in preparations precontracted by 9,11‐dideoxy‐11α,9α‐epoxymethanoprostaglandin F2α (U‐46619). Relaxation was reduced by ruthenium red while it was enhanced by HC‐030031. In conclusion, NPB has vasodilator properties but with a mechanism of action distinct from its analogues. Contrary to other nitro compounds, its relaxing effects did not involve recruitment of the guanylyl cyclase pathway. NPB has also endothelium‐dependent potentiating properties on phenylephrine‐induced contractions, a phenomenon that putatively required a role of endothelial TRPA₁ channels. The present findings reinforce the notion that the functional group NO₂ in the aliphatic chain of these nitro compounds determines favorably their vasodilator properties.     

What Does 2‐Dimensional Imaging Add to 3‐ and 4‐Dimensional Obstetric Ultrasonography?

OBJECTIVE: The purpose of this study was to determine whether 2-dimensional (2D) ultrasonography adds diagnostic information to that provided by the examination of 3-dimensional/4-dimensional (3D/4D) volume data sets alone. METHODS: Ninety-nine fetuses were examined by 3D/4D volume ultrasonography. Volume data sets were evaluated by a blinded independent examiner who, after establishing an initial diagnostic impression by 3D/4D ultrasonography, performed a 2D ultrasonographic examination. The frequency of agreement and diagnostic accuracy of each modality to detect congenital anomalies were calculated and compared. RESULTS: Fifty-four fetuses with no abnormalities and 45 fetuses with 82 anomalies diagnosed by 2D ultrasonography were examined. Agreement between 3D/4D and 2D ultrasonography occurred for 90.4% of the findings (123/136; intraclass correlation coefficient, 0.834; 95% confidence interval, 0.774-0.879). Six anomalies were missed by 3D/4D ultrasonography when compared to 2D ultrasonography (ventricular septal defect [n = 2], interrupted inferior vena cava with azygous continuation [n = 1], tetralogy of Fallot [n = 1], horseshoe kidney [n = 1], and cystic adenomatoid malformation [n = 1]). There were 2 discordant diagnoses: transposition of the great arteries diagnosed as a double-outlet right ventricle and pulmonary atresia misinterpreted as tricuspid atresia on 3D/4D ultrasonography. One case of occult spinal dysraphism was suspected on 3D ultrasonography but not confirmed by 2D ultrasonography. When compared to diagnoses performed after delivery (n = 106), the sensitivity and specificity of 3D/4D ultrasonography (92.2% [47/51] and 76.4% [42/55], respectively) and 2D ultrasonography (96.1% [49/51] and 72.7% [40/55]) were not significantly different (P = .233). CONCLUSIONS: Information provided by 2D ultrasonography is consistent, in most cases, with information provided by the examination of 3D/4D volume data sets alone.     

Synthesis and characterization of poly(glycerol‐co‐sebacate‐co‐ε‐caprolactone) elastomers

In this study, poly(glycerol‐co‐sebacate‐co‐ε‐caprolactone) (PGSCL) elastomers were synthesized for the first time from the respective monomers. The structural analysis of PGSCL elastomers by nuclear magnetic resonance (¹H‐NMR) and Fourier transform infrared spectroscopy (FTIR) revealed that the elastomers have a high number of hydrogen bonds and crosslinks. X‐ray diffraction (XRD) and thermal analysis indicated an amorphous state. Differential scanning calorimetry (DSC) analysis showed that the elastomers has a glass transition temperature (T_g) of –36.96°C. The Young's modulus and compression strength values were calculated as 46.08 MPa and 3.192 MPa, respectively. Calculations based on acid number and end groups analysis revealed a number average molecular weight of 148.15 kDa. Even though the foaming studies conducted by using supercritical CO₂ resulted in a porous structure; the obtained morphology tended to disappear after 48 h, leaving small cracks on the surface. This phenomenon was interpreted as an indication of self‐healing due to the high number of hydrogen bonds. The PGSCL elastomers synthesized in this study are flexible, robust to compression forces and have self‐healing capacity. Thanks to good biocompatibility and poor cell‐adhesion properties, the elastomers may find diverse applications where a postoperative adhesion barrier is required. Copyright © 2013 John Wiley & Sons, Ltd.     

D‐ and L‐[123I]‐2‐I‐phenylalanine show a long tumour retention compared with D‐ and L‐[123I]‐2‐I‐tyrosine in R1M rhabdomyosarcoma tumour‐bearing Wag/Rij rats

The aim of this study was the comparison of the tumour uptake and the long‐term retention of [¹²³I]‐2‐I‐L ‐phenylalanine and [¹²³I]‐2‐I‐D ‐phenylalanine with those of [¹²³I]‐2‐I‐L ‐tyrosine and [¹²³I]‐2‐I‐D ‐tyrosine in R1M rhabdomyosarcoma tumour‐bearing rats. The biodistribution of the radioactivity as a function of time in R1M tumour‐bearing rats was measured by planar gamma camera imaging (dynamic and static). If dissection was applied, the activity in the tumours and tissues of interest was measured by gamma counting. [¹²³I]‐2‐iodo‐L ‐phenylalanine, [¹²³I]‐2‐iodo‐D ‐phenylalaine, [¹²³I]‐2‐I‐L ‐tyrosine showed a considerable tumour uptake reaching a maximum between 10 and 30 min. At 30 min p.i. the differential uptake ratio values of this uptake were, respectively, 2.1, 2.3, 2.5 and 1.7. The activity in the tumour was shown to be related to a tumour cell uptake and not to an increased blood pool activity. All the tracers showed a clearance from the blood to the bladder without renal retention. At longer times both L ‐ and D ‐ [¹²³I]‐2‐I‐tyrosine were cleared for a large part from the tumours and the body. [¹²³I]‐2‐I‐L ‐Phe and [¹²³I]‐2‐I‐D ‐Phe showed a considerable and equal retention in the tumours: as compared with 0.5 h, 91% at 24 h and 80% at 48 h. This was related to the longer retention of activity in the blood pool noticed for these compounds (81% at 24 h and 65% at 48 h). The tumour‐to‐background ratio increased with 25% at those longer times. At short times all the tracers were taken up to a considerable extent in the tumours. In the R1M‐bearing Wag/Rij rat model only [¹²³I]‐2‐I‐L ‐phenylalanine and [¹²³I]‐2‐I‐D ‐phenylalanine showed an especially high retention at long times without any significant difference between the enantiomers. Copyright © 2007 John Wiley & Sons, Ltd.