Regional anesthesia nerve blocks are increasingly used for patients undergoing cardiac surgery as part of multimodal pain management. Though rare, local anesthetic systemic toxicity (LAST) is a severe complication that requires vigilant monitoring. We present a case of a postcardiac surgery patient who developed LAST multiple days after surgery from lidocaine via an erector spinae plane catheter.
View Article and Find Full Text PDFBackground: Several studies have shown that American genotype dengue 2 viruses (DENV2) have reduced viral fitness in the mosquito vector, Aedes aegypti, compared to other DENV2 genotypes. Diminished replication efficiency or inability to efficiently traverse membrane barriers encompassing organs such as the midgut or salivary glands are considered major factors negatively impacting viral fitness in the mosquito.
Results: We analyzed the vector competence of Ae.
The homeodomain transcription factor pancreas duodenal homeobox 1 (Pdx1, also known as insulin promoter factor 1) is a master regulator of pancreas development, as mice or humans lacking Pdx1 function are a pancreatic. Importantly, heterozygous mutations in Pdx1 cause early and late onset forms of diabetes in humans. Despite these central roles in development and adult β-cell function, we have only rudimentary knowledge of the transcriptome targets of Pdx1 that mediate these phenotypes.
View Article and Find Full Text PDFHyperglycemia increases insulin flux through the endoplasmic reticulum (ER) of pancreatic β-cells, and the unfolded protein response pathway is required to enhance insulin processing. Pancreatic and duodenal homeobox 1 (PDX1), a key pancreatic transcription factor, regulates insulin along with targets involved in insulin processing and secretion. Here we find that PDX1 is a direct transcriptional regulator of ER oxidoreductin-1-like β (Ero1lβ), which maintains the oxidative environment of the ER to facilitate disulfide bond formation.
View Article and Find Full Text PDFBackground: The RNA interference (RNAi) pathway acts as an innate antiviral immune response in Aedes aegypti, modulating arbovirus infection of mosquitoes. Sindbis virus (SINV; family: Togaviridae, genus: Alphavirus) is an arbovirus that infects Ae. aegypti in the laboratory.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
November 2009
Type 2 diabetes mellitus (T2DM) results from pancreatic beta cell failure in the setting of insulin resistance. Heterozygous mutations in the gene encoding the beta cell transcription factor pancreatic duodenal homeobox 1 (Pdx1) are associated with both T2DM and maturity onset diabetes of the young (MODY4), and low levels of Pdx1 accompany beta cell dysfunction in experimental models of glucotoxicity and diabetes. Here, we find that Pdx1 is required for compensatory beta cell mass expansion in response to diet-induced insulin resistance through its roles in promoting beta cell survival and compensatory hypertrophy.
View Article and Find Full Text PDFThe canonical Wnt-beta-catenin signaling pathway is initiated by inducing phosphorylation of one of the Wnt receptors, low-density lipoprotein receptor-related protein 6 (LRP6), at threonine residue 1479 (Thr1479) and serine residue 1490 (Ser1490). By screening a human kinase small interfering RNA library, we identified phosphatidylinositol 4-kinase type II alpha and phosphatidylinositol-4-phosphate 5-kinase type I (PIP5KI) as required for Wnt3a-induced LRP6 phosphorylation at Ser1490 in mammalian cells and confirmed that these kinases are important for Wnt signaling in Xenopus embryos. Wnt3a stimulates the formation of phosphatidylinositol 4,5-bisphosphates [PtdIns (4,5)P2] through frizzled and dishevelled, the latter of which directly interacted with and activated PIP5KI.
View Article and Find Full Text PDFHagen's glands of males of the parasitic wasp Diachasmimorpha longicaudata (Hymenoptera: Braconidae) secrete compounds that are involved in courtship and defense. Like the poison glands of female wasps, the Hagen's glands are secretory, membranous, and of ectodermal origin. The poison glands contain the symbiotic entomopoxvirus, DlEPV and the parasitism-specific protein, PSP 24.
View Article and Find Full Text PDFIntracellular Wolbachia bacteria are obligate, maternally inherited endosymbionts found frequently in insects and other invertebrates. The evolutionary success of Wolbachia is due in part to an ability to manipulate reproduction. In mosquitoes and many other insects, Wolbachia causes a form of sterility known as cytoplasmic incompatibility (CI).
View Article and Find Full Text PDFA proposed strategy to aid in controlling the growing burden of vector-borne disease is population replacement, in which a natural vector population is replaced by a population with a reduced capacity for disease transmission. An important component of such a strategy is the drive system, which serves to spread a desired genotype into the targeted field population. Endosymbiotic Wolbachia bacteria are potential transgene drivers, but infections do not naturally occur in some important mosquito vectors, notably Aedes aegypti.
View Article and Find Full Text PDFSexually mature males of Bactrocera papayae are strongly attracted to and consume methyl eugenol (ME). Upon consumption, ME is biotransformed to two phenylpropanoids, 2-allyl-4,5-dimethoxyphenol (DMP) and (E)-coniferyl alcohol (CF), that are transported in the hemolymph, sequestered and stored in the rectal glands, and subsequently released as sex and aggregation pheromones during courtship. To date, very little work on the ultrastructure and anatomy of the rectal gland has been done, and the accumulation of phenylpropanoids in the rectal glands of males has not been observed visually.
View Article and Find Full Text PDFGenetic strategies that reduce or block pathogen transmission by mosquitoes are being investigated as a means to augment current control measures. Strategies of vector suppression and replacement are based upon intracellular Wolbachia bacteria, which occur naturally in many insect populations. Maternally inherited Wolbachia have evolved diverse mechanisms to manipulate host insect reproduction and promote infection invasion.
View Article and Find Full Text PDFThe aim of the present study was to prepare controlled-release tablets of poorly-soluble drug, felodipine. Spray chilling was used to formulate the drug, the polar lipids and the hydrophilic polymers into solid dispersion microparticles, which were then compressed. The microparticles were characterised by Fourier transform infrared and Raman spectroscopies, X-ray powder diffraction, hot-stage microscopy, scanning electron microscopy, and image analysis.
View Article and Find Full Text PDFChitosan blends with hydrophilic polymers including polyvinylalcohol (PVA), polyethyleneoxide (PEO) and polyvinylpyrrolidone (PVP), were investigated as candidates for oral gingival delivery systems. The bioavailabilty conferred by the chitosan blend delivery systems, as concluded from dog studies, was shown to be comparable to that based on chitosan alone, especially for those blends involving high molecular weight hydrophilic polymers. Results from differential scanning calorimetry and dynamic mechanical thermal analysis, Fourier transform infrared spectroscopy and tensile testing, indicated that the chitosan/PEO and chitosan/PVP blends showed evidence of miscibility in all blend ratios studied, while the chitosan/PVA blend only showed evidence of interaction for the (50:50) and (80:20) blends, but not for the (20:80) blend.
View Article and Find Full Text PDFFormation of solid solution particles in the Solution Enhanced Dispersion by Supercritical fluids (SEDS) process from a model drug and two different types of carriers, mannitol and Eudragit E100 was evaluated. The crystal properties of samples and molecular interactions were investigated with DSC and FTIR, respectively. The effect of co-crystallisation of drug and mannitol on dissolution rate was studied.
View Article and Find Full Text PDFThe aim of the present study was to prepare controlled-release tablets of poorly-soluble drug, felodipine, and various erodable lipophilic excipients. Spray chilling was used to formulate the drug and the excipients into solid dispersion microparticles, which were then compressed. The microparticles were characterised by Fourier transform infrared spectroscopy, hot-stage microscopy, scanning electron microscopy, and image analysis.
View Article and Find Full Text PDF