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Find video protocols related to scientific articles indexed in Pubmed.
Short-term effects of oral administration of Pistacia lentiscus oil on tissue-specific toxicity and drug metabolizing enzymes in mice.
Cell. Physiol. Biochem.
PUBLISHED: 03-17-2014
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Pistacia lentiscus (Anacardiaceae) is a flowering plant traditionally used in the treatment of various skin, respiratory, and gastrointestinal disorders. The aim of this study was to assess whether Pistacia lentiscus oil has any short term toxic effects in vivo and in vitro.
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Knowledge and Attitudes of Oman Medical Specialty Board Residents towards Evidence-Based Medicine.
Oman Med J
PUBLISHED: 02-14-2014
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This study aims to evaluate the knowledge and attitudes of Oman Medical Specialty Board (OMSB) residents towards Evidence-Based Medicine (EBM).
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Polyethylene glycol conjugated polymeric nanocapsules for targeted delivery of quercetin to folate-expressing cancer cells in vitro and in vivo.
ACS Nano
PUBLISHED: 01-23-2014
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In this work we describe the formulation and characterization of chemically modified polymeric nanocapsules incorporating the anticancer drug, quercetin, for the passive and active targeting to tumors. Folic acid was conjugated to poly(lactide-co-glycolide) (PLGA) polymer to facilitate active targeting to cancer cells. Two different methods for the conjugation of PLGA to folic acid were employed utilizing polyethylene glycol (PEG) as a spacer. Characterization of the conjugates was performed using FTIR and (1)H NMR studies. The PEG and folic acid content was independent of the conjugation methodology employed. PEGylation has shown to reduce the size of the nanocapsule; moreover, zeta-potential was shown to be polymer-type dependent. Comparative studies on the cytotoxicity and cellular uptake of the different formulations by HeLa cells, in the presence and absence of excess folic acid, were carried out using MTT assay and Confocal Laser Scanning Microscopy, respectively. Both results confirmed the selective uptake and cytotoxicity of the folic acid targeted nanocapsules to the folate enriched cancer cells in a folate-dependent manner. Finally, the passive tumor accumulation and the active targeting of the nanocapsules to folate-expressing cells were confirmed upon intravenous administration in HeLa or IGROV-1 tumor-bearing mice. The developed nanocapsules provide a system for targeted delivery of a range of hydrophobic anticancer drugs in vivo.
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Discovery of familial cerebral cavernous malformation in a Saudi population.
BMJ Case Rep
PUBLISHED: 11-23-2013
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Familial cerebral cavernous malformation is a rare entity. It has been described commonly among the Hispanic population and sparsely among the Italian, French, Swedish and Chinese populations. We discovered two families with this condition among the Saudi population for the first time. Both the index patients had a seizure as a prominent manifestation of their underlying structural lesion. One of them had recurrent attacks of bleeding in the cavernoma leading to a focal neurological deficit. The siblings and the parents of both the patients were screened using CT of the brain imaging. Two members within each family were found to have symptomatic cavernoma. A molecular genetics study revealed heterozygous KRIT1/CCM1 for a frameshift mutation in one of the patients. No detectable mutation was found in the other patient. These cases illustrate the existence of this condition beyond the commonly known geographical area of higher prevalence. Moreover, KRIT1/CCM1 might be the possible target gene that is mutated in this region.
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Transmission and evolution of the Middle East respiratory syndrome coronavirus in Saudi Arabia: a descriptive genomic study.
Lancet
PUBLISHED: 09-20-2013
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Since June, 2012, Middle East respiratory syndrome coronavirus (MERS-CoV) has, worldwide, caused 104 infections in people including 49 deaths, with 82 cases and 41 deaths reported from Saudi Arabia. In addition to confirming diagnosis, we generated the MERS-CoV genomic sequences obtained directly from patient samples to provide important information on MERS-CoV transmission, evolution, and origin.
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Combined liver and kidney transplantation in primary hyperoxaluria: a report of three cases and review of the literature.
Saudi J Kidney Dis Transpl
PUBLISHED: 09-14-2013
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Primary hyperoxaluria type-1 (PH-1) is a rare autosomal recessive metabolic disorder leading to excessive oxalate production, deposition of calcium oxalate crystals in the kidney, nephrocalcinosis, progressive renal failure and systemic deposition of oxalate (oxalosis). Combined liver and kidney transplantation (LKT), which has been accepted as the treatment of choice for PH-1, has considerably improved patient and graft survival. Herein, we report our experience of three children with PH-1 who underwent combined LKT, with a review of the literature.
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Epidemiological, demographic, and clinical characteristics of 47 cases of Middle East respiratory syndrome coronavirus disease from Saudi Arabia: a descriptive study.
Lancet Infect Dis
PUBLISHED: 07-26-2013
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Middle East respiratory syndrome (MERS) is a new human disease caused by a novel coronavirus (CoV). Clinical data on MERS-CoV infections are scarce. We report epidemiological, demographic, clinical, and laboratory characteristics of 47 cases of MERS-CoV infections, identify knowledge gaps, and define research priorities.
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Impaired NADPH oxidase activity in peripheral blood lymphocytes of galactosemia patients.
Exp. Biol. Med. (Maywood)
PUBLISHED: 07-04-2013
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Galactosemia is an autosomal recessive disorder with a wide range of clinical abnormalities. Cellular oxidative stress is considered as one of the pathogenic mechanisms of galactosemia. In this study, we examined the activity of NADPH oxidase (NOX), a major superoxide-generating enzyme system, in peripheral blood lymphocytes (PBL) from galactosemia patients. PBL were isolated from galactosemia patients and healthy control subjects and used for cell culture studies and biochemical assays. PBL were cultured in the presence or absence of galactose or galactose-1-phosphate (Gal-1-P), and enzyme activities and/or gene expression of NOX, catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured in the cell homogenates. PBL isolated from galactosemia patients showed significantly reduced (P < 0.01) activities of catalase and GPx; however SOD activity remained unaltered. Galactosemia patients were found to have significantly (P < 0.01) increased levels of malondialdehyde (MDA) in blood lymphocytes. Enzymatic activity of NOX was significantly (P < 0.001) reduced in galactosemia patients; however, Western blotting revealed that NOX-1 protein was not significantly altered. Interestingly, levels of NOX activity in lymphocytes isolated from galactosemia patients significantly increased but remained subnormal when cultured in galactose-deficient medium for two weeks, indicating a galactose-mediated inhibition of NOX. Lymphocytes isolated from control subjects were found to have significantly (P < 0.01) reduced NOX activity when cultured in the presence of galactose or Gal-1-P for two weeks. These results show that galactose-induced cellular oxidative stress is not NOX mediated. However, impairment of the NOX system might be responsible for some of the clinical complications in galactosemia patients.
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Assessment of Truflex™ articulating stylet versus conventional rigid Portex™ stylet as an intubation guide with the D-blade of C-Mac™ videolaryngoscope during elective tracheal intubation: study protocol for a randomized controlled trial.
Trials
PUBLISHED: 03-18-2013
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A variety of videolaryngoscopes with angulated blade have been recently introduced into clinical practice. They provide an indirect view of the glottic structures in normal and challenging clinical settings. Despite the very good visualization of the laryngeal structures by these devices, the insertion and advancement of the endotracheal tube may be prolonged and occasionally fail as it does not conform to the enhanced angulation of the blade. To overcome this handicap, it is recommended to use a pre-shaped, styleted tracheal tube during intubation. Unfortunately, these malleable rigid stylets permit only a fixed shape to the advancing endotracheal tube. This may necessitate withdrawal of endotracheal tube-stylet assembly for reshaping, before undertaking a new attempt. This may cause soft tissue injury and hemodynamic disturbance.This single-blinded randomized clinical trial aims to overcome these handicaps using a novel method of dynamically changing the shape of the advancing endotracheal tube by Truflex™ articulating stylet as per need during D-blade C-Mac™ videolaryngoscopy.
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Cationic poly-L-lysine dendrimer complexes doxorubicin and delays tumor growth in vitro and in vivo.
ACS Nano
PUBLISHED: 03-07-2013
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We report in this study the complexation of the chemotherapeutic drug doxorubicin (DOX) with the novel sixth-generation cationic poly-l-lysine dendrimer (DM) (MW 8149 kDa), which we previously reported to exhibit systemic antiangiogenic activity in tumor-bearing mice. DOX-DM complexation was confirmed by florescence polarization measurement, proton nuclear magnetic resonance spectroscopy, and molecular modeling. Enhanced penetration of DOX-DM (at 1:10 molar ratio), compared to the free DOX, into prostate 3D multicellular tumor spheroids (MTS) was confirmed by confocal laser scanning microscopy. Furthermore, DOX-DM complexes achieved a significantly higher cytotoxicity in DU145 MTS system compared to the free drug, as shown by growth delay curves. Incubation of MTS with low DOX concentration (1 ?M) complexed with DM led to a significant delay in MTS growth compared to untreated MTS or MTS treated with free DOX. DOX-DM complex retention was also achieved in a Calu-6 lung cancer xenograft model in tumor-bearing mice, as shown by live whole animal fluorescence imaging. Therapeutic experiments in B16F10 tumor bearing mice have shown enhanced therapeutic efficacy of DOX when complexed to DM. This study suggests that the cationic poly-l-lysine DM molecules studied here could, in addition to their systemic antiangiogenic property, complex chemotherapeutic drugs such as DOX and improve their accumulation and cytotoxicity into MTS and solid tumors in vivo. Such an approach offers new capabilities for the design of combinatory antiangiogenic/anticancer therapeutics.
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Autophagy and formation of tubulovesicular autophagosomes provide a barrier against nonviral gene delivery.
Autophagy
PUBLISHED: 02-19-2013
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Cationic liposome (lipoplex) and polymer (polyplex)-based vectors have been developed for nonviral gene delivery. These vectors bind DNA and enter cells via endosomes, but intracellular transfer of DNA to the nucleus is inefficient. Here we show that lipoplex and polyplex vectors enter cells in endosomes, activate autophagy and generate tubulovesicular autophagosomes. Activation of autophagy was dependent on ATG5, resulting in lipidation of LC3, but did not require the PtdIns 3-kinase activity of PIK3C3/VPS34. The autophagosomes generated by lipoplex fused with each other, and with endosomes, resulting in the delivery of vectors to large tubulovesicular autophagosomes, which accumulated next to the nucleus. The tubulovesicular autophagosomes contained autophagy receptor protein SQSTM1/p62 and ubiquitin, suggesting capture of autophagy cargoes, but fusion with lysosomes was slow. Gene delivery and expression from both lipoplex and polyplex increased 8-fold in atg5 (-/-) cells unable to generate tubulovesicular autophagosomes. Activation of autophagy and capture within tubulovesicular autophagosomes therefore provides a new cellular barrier against efficient gene transfer and should be considered when designing efficient nonviral gene delivery vectors.
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Mutations in NALCN cause an autosomal-recessive syndrome with severe hypotonia, speech impairment, and cognitive delay.
Am. J. Hum. Genet.
PUBLISHED: 02-07-2013
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Sodium leak channel, nonselective (NALCN) is a voltage-independent and cation-nonselective channel that is mainly responsible for the leaky sodium transport across neuronal membranes and controls neuronal excitability. Although NALCN variants have been conflictingly reported to be in linkage disequilibrium with schizophrenia and bipolar disorder, to our knowledge, no mutations have been reported to date for any inherited disorders. Using linkage, SNP-based homozygosity mapping, targeted sequencing, and confirmatory exome sequencing, we identified two mutations, one missense and one nonsense, in NALCN in two unrelated families. The mutations cause an autosomal-recessive syndrome characterized by subtle facial dysmorphism, variable degrees of hypotonia, speech impairment, chronic constipation, and intellectual disability. Furthermore, one of the families pursued preimplantation genetic diagnosis on the basis of the results from this study, and the mother recently delivered healthy twins, a boy and a girl, with no symptoms of hypotonia, which was present in all the affected children at birth. Hence, the two families we describe here represent instances of loss of function in human NALCN.
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Small ruminant lentiviruses in Jordan: evaluation of sheep and goat serological response using recombinant and peptide antigens.
Trop Anim Health Prod
PUBLISHED: 01-28-2013
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Small ruminant lentiviruses infect sheep and goats worldwide, causing chronic progressive diseases and relevant economic losses. Disease eradication and prevention is mostly based on serological testing. The goal of this research was to investigate the presence of the small ruminant lentiviruses (SRLVs) in Jordan and to characterize the serological response in sheep and goat populations. A panel of sera were collected from flocks located in Northern Jordan and Jordan Valley. The samples were tested using three ELISA assays: a commercially available ELISA based on p25 recombinant protein and transmembrane peptide derived from British maedi-visna virus (MVV) EV1 strain, an ELISA based on P16-P25 recombinant protein derived from two Italian strains representative of MVV- and caprine arthritis encephalitis virus (CAEV)-like SRLVs, and an ELISA based on SU5 peptide from the same two Italian isolates. The results indicate that both MVV- and CAEV-like strains are present in Jordan and that the majority of the viruses circulating among sheep and goat populations belong to the MVV-like genotype.
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Assessment of central corneal thickness and corneal endothelial morphology using ultrasound pachymetry, non-contact specular microscopy, and Confoscan 4 confocal microscopy.
BMC Ophthalmol
PUBLISHED: 01-18-2013
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The aim was to compare the repeatability, reproducibility and inherent precision of ultrasound pachymetry (USP), noncontact specular microscopy (SP-2000P) and the Confoscan 4 confocal microscope (z-ring CS4) in measuring endothelial cell density (ECD), coefficient of variation of cell size (CV), and central corneal thickness (CCT) in normal eyes.
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Maternal near miss and quality of maternal health care in Baghdad, Iraq.
BMC Pregnancy Childbirth
PUBLISHED: 01-16-2013
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The maternal near-miss concept has been developed as an instrument for assisting health systems to evaluate and improve their quality of care. Our study aimed at studying the characteristics and quality of care provided to women with severe complications in Baghdad through the use of the World Health Organization (WHO) near-miss approach for maternal health.
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Microbial consortia in Oman oil fields: a possible use in enhanced oil recovery.
J. Microbiol. Biotechnol.
PUBLISHED: 01-15-2013
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Microbial enhanced oil recovery (MEOR) is one of the most economical and efficient methods for extending the life of production wells in a declining reservoir. Microbial consortia from Wafra oil wells and Suwaihat production water, Al-Wusta region, Oman were screened. Microbial consortia in brine samples were identified using denaturing gradient gel electrophoresis and 16S rRNA gene sequences. The detected microbial consortia of Wafra oil wells were completely different from microbial consortia of Suwaihat formation water. A total of 33 genera and 58 species were identified in Wafra oil wells and Suwaihat production water. All of the identified microbial genera were first reported in Oman, with Caminicella sporogenes for the first time reported from oil fields. Most of the identified microorganisms were found to be anaerobic, thermophilic, and halophilic, and produced biogases, biosolvants, and biosurfactants as by-products, which may be good candidates for MEOR.
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Inflammatory bowel disease in children, an evolving problem in Kuwait.
Saudi J Gastroenterol
PUBLISHED: 09-14-2011
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Inflammatory bowel disease (IBD) was previously thought a rare disease among children in Kuwait since most diarrhea cases were attributed to infections. In the past few years we observed an increase in the number of patients presenting with IBD. In this study we aimed to determine the epidemiology of IBD among children in the State of Kuwait.
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Liposomes: from a clinically established drug delivery system to a nanoparticle platform for theranostic nanomedicine.
Acc. Chem. Res.
PUBLISHED: 08-03-2011
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For decades, clinicians have used liposomes, self-assembled lipid vesicles, as nanoscale systems to deliver encapsulated anthracycline molecules for cancer treatment. The more recent proposition to combine liposomes with nanoparticles remains at the preclinical development stages; however, such hybrid constructs present great opportunities to engineer theranostic nanoscale delivery systems, which can combine simultaneous therapeutic and imaging functions. Many novel nanoparticles of varying chemical compositions are being developed in nanotechnology laboratories, but further chemical modification is often required to make these structures compatible with the biological milieu in vitro and in vivo. Such nanoparticles have shown promise as diagnostic and therapeutic tools and generally offer a large surface area that allows covalent and non-covalent surface functionalization with hydrophilic polymers, therapeutic moieties, and targeting ligands. In most cases, such surface manipulation diminishes the theranostic properties of nanoparticles and makes them less stable. From our perspective, liposomes offer structural features that can make nanoparticles biocompatible and present a clinically proven, versatile platform for further enhancement of the pharmacological and diagnostic efficacy of nanoparticles. In this Account, we describe two examples of liposome-nanoparticle hybrids developed as theranostics: liposome-quantum dot hybrids loaded with a cytotoxic drug (doxorubicin) and artificially enveloped adenoviruses. We incorporated quantum dots into lipid bilayers, which rendered them dispersible in physiological conditions. This overall vesicular structure allowed them to be loaded with doxorubicin molecules. These structures exhibited cytotoxic activity and labeled cells both in vitro and in vivo. In an alternative design, lipid bilayers assembled around non-enveloped viral nanoparticles and altered their infection tropism in vitro and in vivo with no chemical or genetic capsid modifications. Overall, we have attempted to illustrate how alternative strategies to incorporate nanoparticles into liposomal nanostructures can overcome some of the shortcomings of nanoparticles. Such hybrid structures could offer diagnostic and therapeutic combinations suitable for biomedical and even clinical applications.
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Ribosomal DNA sequence characterization of Maritrema cf. eroliae Yamaguti, 1939 (Digenea: Microphallidae) and its life cycle.
J. Parasitol.
PUBLISHED: 07-25-2011
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The microphallid Maritrema eroliae parasitizes shore birds in marine ecosystems while its larval stages infect mud snails and crustacean hosts. Because it is difficult to morphologically distinguish between larvae of M. eroliae and other microphallids co-occurring in the same habitat, partial nucleotide sequences of the ribosomal DNA (rDNA), including the 28S and 18S in addition to complete sequences of ITS1 and ITS2, were scrutinized. This analysis was used to establish the snail-crab link in the life cycle of M. cf. eroliae . The rDNA 28S, 18S, and ITS sequences of metacercariae from the crab Xantho exaratus and sporocysts from the snail Clypeomorus bifasciata were compared. Sequence alignment demonstrated that the sporocyst and metacercaria may belong to M. eroliae and suggested a new second intermediate host for M. eroliae , the crab X. exaratus . The phylogenetic positions of the larval stages were determined by comparing the 28S, 18S, and ITS sequences with those of other trematodes available in GenBank. The phylogenetic trees confirmed the position of M. cf. eroliae within the Microphallidae and found it to be closely related to Maritrema heardi and Maritrema neomi. The present study represents the first molecular study correlating the larval stages in the life cycle of M. cf. eroliae using partial sequences of 28S and 18S in addition to complete ITS1 and ITS2 sequences. Furthermore, the sequences elucidated the evolutionary relationship of M. cf. eroliae to other microphallids.
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Adverse effects of oral nonstimulant psychotropic medications in young children reported to a regional poison center.
Clin Toxicol (Phila)
PUBLISHED: 05-27-2011
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Use of nonstimulant psychotropic medications other than antidepressants in young children is reported to be increasing. The patient safety ramifications of this remain unclear.
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Setting up of teeth in the neutral zone and its effect on speech.
Saudi Dent J
PUBLISHED: 04-21-2011
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Rational goals for denture construction are basically directed at the restoration of esthetics and masticatory function and the healthy preservation of the remaining natural tissues. Little concern has been given to the perfection and optimization of the phonetic quality of denture users. However, insertion of prosthodontic restorations may lead to speech defects. Most such defects are mild but, nevertheless, can be a source of concern to the patient. For the dental practitioner, there are few guidelines for designing a prosthetic restoration with maximum phonetic success. One of these guidelines involves the setting up of teeth within the neutral zone. The aim of this study was to evaluate, subjectively and objectively, the effect on speech of setting up teeth in the neutral zone. Three groups were examined: group I (control) included 10 completely dentulous subjects, group II included 10 completely edentulous patients with conventional dentures, and group III included the same 10 edentulous patients with neutral zone dentures. Subjective assessment included patient satisfaction. Objective assessment included duration taken for recitation of Al-Fateha and acoustic analysis. Subjectively, patients were more satisfied with their neutral zone dentures. Objectively, speech produced with the neutral zone dentures was closer to normal than speech with conventional dentures.
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Status epilepticus associated with borage oil ingestion.
J Med Toxicol
PUBLISHED: 03-10-2011
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The use of herbal and complementary medicine is common. Many herbal products are known to produce serious adverse effects. Borage oil is derived from the seeds of the borage plant (Borago officinalis) an abundant source of gamma-linolenic acid (GLA), and Borage oil has been promoted as a treatment for rheumatoid arthritis, atopic dermatitis, diabetic neuropathy, and menopause-related symptoms. We report a case of status epilepticus in a patient who consumed borage oil for one week.
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Ovarian salvage in bilaterally complicated severe ovarian hyperstimulation syndrome.
Fertil. Steril.
PUBLISHED: 03-09-2011
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To report the management of 2 cases of severe ovarian hyperstimulation syndrome (OHSS) bilaterally complicated by rupture and late subsequent torsion.
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Cellular oxidative stress and peroxisomal enzyme activities in pediatric liver transplant patients.
Med Princ Pract
PUBLISHED: 03-03-2011
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In this study, we examined the activities of key peroxisomal enzymes in peripheral blood lymphocytes (PBLs) of pediatric liver transplant patients.
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Intracellular trafficking and gene expression of pH-sensitive, artificially enveloped adenoviruses in vitro and in vivo.
Biomaterials
PUBLISHED: 01-26-2011
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Recombinant adenovirus (Ad) has shown great promise in gene therapy. Artificial envelopment of adenovirus within lipid bilayers has previously been shown to decrease the immunogenicity and hepatic affinity of naked Ad in vivo. Unfortunately, this also resulted in a significant reduction of gene expression, which we attributed to poor endosomal release of the Ad from its artificial lipid envelope. In this work, we explored the artificial envelopment of Ad within pH-sensitive DOPE:CHEMS bilayers and characterized this vector by TEM, AFM, dot blot, dynamic light scattering and zeta potential measurements. The artificially enveloped viral vectors exhibited good stability at physiological pH but immediately collapsed and released naked Ad virions at pH 5.5. Intracellular trafficking using confocal laser scanning microscopy (CLSM) revealed that Cy3-labelled Ad enveloped in DOPE:CHEMS bilayers exhibited the characteristic Ad distribution within the cytoplasm that led to virion accumulation around the nuclear membrane, indicating endosomal release of Ad. We obtained equivalent levels of gene expression as those of naked Ad in a series of CAR-positive (CAR+) and CAR-negative (CAR-) cell lines. This suggested that the mechanism of infection for the artificially enveloped Ad remained dependent on the presence of CAR receptors. Finally, the pH-sensitive enveloped Ad were injected intratumorally in human cervical carcinoma xenograft-bearing nude mice, also illustrating their capacity for efficient in vivo marker gene expression. This study is a step forward toward the engineering of functional, artificially enveloped adenovirus vectors for gene transfer applications.
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A founder effect at the EPCAM locus in Congenital Tufting Enteropathy in the Arabic Gulf.
Eur J Med Genet
PUBLISHED: 01-25-2011
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Mutations of the EPCAM gene have been recently identified in Congenital Tufting Enteropathy (CTE), a severe autosomal recessive gastrointestinal insufficiency of childhood requiring parenteral nutrition and occasionally intestinal transplantation. Studying seven multiplex consanguineous families from the Arabic peninsula (Kuwait and Qatar) we found that most patients were homozygote for a c.498insC mutation in exon 5. The others carried a novel mutation IVS4-2A?G. Both mutations were predicted to truncate the C-terminal domain necessary to anchorage of EPCAM at the intercellular membrane. Consistently, immunohistochemistry of intestinal biopsies failed to detect the EPCAM protein at the intercellular membrane level. The c.498insC mutation was found on the background of a minimal common haplotype of 473kb suggesting a very old founder effect (5000-6000 yrs).
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Doxorubicin-loaded lipid-quantum dot hybrids: surface topography and release properties.
Int J Pharm
PUBLISHED: 01-22-2011
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A few studies have attempted to combine the physicochemical versatility offered by the liposome structure with the superior optical characteristics of quantum dots (QD) for the construction of multifunctional nanoparticles. We are reporting the construction of drug-loaded liposome-QD hybrid vesicles (L-QD) by incorporating TOPO-capped, CdSe/ZnS QD into the two types of lipid bilayers: the rigid disteroylphosphatidylcholine (DSPC:Chol:DSPE-PEG(2000)) and a fluid-phase bilayer of egg PC (EPC:Chol:DSPE-PEG(2000)). Structural characterization of L-QD hybrid vesicles using atomic force microscopy (AFM) revealed that the incorporation of QD took place by hydrophobic self-association within the membranes. The encapsulation of hydrophilic small molecules in the internal aqueous phase of the L-QD hybrids showed different degrees of carboxyfluorescein (CF) release in buffer and serum, depending on the type of lipid used. The presence of QD in the lipid bilayer increased the CF release from EPC fluid bilayer. On the other hand, (DSPC) L-QD hybrids showed a higher stability under the same conditions with minimal CF leakage. Furthermore, (DSPC) L-QD hybrids showed a stable mean diameter up to three weeks stored at 4°C, 25°C, and 40°C, determined by photo correlation spectroscopy (PCS) analysis. Finally, doxorubicin (Dox) was loaded into L-QD hybrids using the osmotic gradient technique and with at least 97% loading efficiency. The fluorescence spectrum of Dox was simultaneously detected with that of green-emitting QD that indicated the coexistence of QD and Dox in a single vesicle system. In conclusion, the drug-loaded L-QD-Dox hybrid vesicles presented here constitute a promising multifunctional delivery vector capable of transporting combinations of therapeutic and diagnostic modalities.
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Intestinal parasites infection among immunocompromised patients in Riyadh, Saudi Arabia.
Pak. J. Biol. Sci.
PUBLISHED: 09-15-2010
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This study was conducted to determine the prevalence of intestinal parasites among immunocompromised patients in Riyadh, Saudi Arabia. Fecal samples were collected from 136 immunocompromised patients (52 females and 84 males), aged 2 to 69 years. Specimens were fixed with 10% formalin for 30 min (2-3 g fecal(-1)) and then concentrated by a formalin-ether sedimentation technique. Samples were examined as wet saline mounts and in iodine preparation for detection of protozoan oocysts, cysts, helminthic eggs and larvae. Permanent stained smears were performed for intestinal coccidian parasites by the modified Ziehl-Neelsen technique and the modified trichrome stain. Intestinal parasites were detected in 54 (39.7%) most of them (25.7%) were with diarrhea. More specifically the following parasites were detected Cryptosporidium parvum 11(8.1%), Giardia lamblia 9 (6.6%), Cyclospora cayetanensis 8 (5.9%), Blastocystis hominis 7 (5.2%), Entamoeba histolytica 7 (5.2%), Entamoeba coli 5 (3.7%), Strongyloides stercoralis 3 (2.2%), Ascaris lumbricoides 1 (0.7%), Hymenolepis nana 1 (0.7%), Dicrocoelium dendriticum 1 (0.7%) and Hook worm 1 (0.7%). The most common parasite associated with diarrhea in patients, was C. parvum (p < 0.001), followed by G. lamblia, C. cayetanensis and E. histolytica. However, differences between different age groups were statistically non-significant. Similarly, no significant difference in the infection rate were found between male and female patients.
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Efficient receptor-independent intracellular translocation of aptamers mediated by conjugation to carbon nanotubes.
Chem. Commun. (Camb.)
PUBLISHED: 09-07-2010
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We have covalently grafted aptamers onto carboxylated carbon nanotubes to design a novel vector system that can easily translocate into the cytosol of different cell types independent of receptor-mediated uptake. We propose the use of carbon nanotubes for the efficient intracellular delivery of biologically active aptamers for potential therapeutic applications.
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Enhanced cellular internalization and gene silencing with a series of cationic dendron-multiwalled carbon nanotube:siRNA complexes.
FASEB J.
PUBLISHED: 07-20-2010
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One of the major obstacles to the clinical development of gene silencing by small interfering RNA (siRNA) is its effective cytoplasmic delivery. Carbon nanotubes have been proposed as novel nanomaterials that can offer significant advantages for the intracellular delivery of nucleic acids, such as siRNA. We recently demonstrated in a proof-of-principle study that amino-functionalized multiwalled carbon nanotubes (f-MWNT) can effectively deliver in vivo an siRNA sequence, triggering cell apoptosis that results in human lung xenograft eradication and prolonged survival. In the present study, we demonstrate how a newly synthesized series of polycationic dendron-MWNT constructs with a precisely tailored number of amino functions (dendron generations) can complex and effectively deliver double-stranded siRNA to achieve gene silencing in vitro. A systematic comparison between the f-MWNT series in terms of cellular uptake, cytotoxicity, and siRNA complexation is offered. Significant improvement in siRNA delivery with the dendron-MWNT conjugates is shown, and gene silencing was obtained in 2 human cell lines using 2 different siRNA sequences. The study reveals that through f-MWNT structure-biological function analysis novel nanotube-based siRNA transfer vectors can be designed with minimal cytotoxicity and effective delivery and gene-silencing capabilities.
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Inguinal uterus, fallopian tube, and ovary associated with adult Mayer-Rokitansky-Küster-Hauser syndrome.
Fertil. Steril.
PUBLISHED: 07-13-2010
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To report a case of Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) with a utero-ovarian inguinal hernia, and to present a review of the pertinent literature.
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Spectrum of clinical presentations in familial hemophagocytic lymphohistiocytosis type 5 patients with mutations in STXBP2.
Blood
PUBLISHED: 06-17-2010
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Hemophagocytic lymphohistiocytosis (HLH) is an often-fatal hyperinflammatory syndrome characterized by fever, hepatosplenomegaly, cytopenia, and in some cases hemophagocytosis. Here, we describe the mutation analysis, clinical presentation, and functional analysis of natural killer (NK) cells in patients with mutations in STXBP2 encoding Munc18-2, recently associated with familial HLH type 5. The disease severity among 11 persons studied here was highly variable and, accordingly, age at diagnosis ranged from 2 months to 17 years. Remarkably, in addition to typical manifestations of familial HLH (FHL), the clinical findings included colitis, bleeding disorders, and hypogammaglobulinemia in approximately one-third of the patients. Laboratory analysis revealed impairment of NK-cell degranulation and cytotoxic capacity. Interleukin-2 stimulation of lymphocytes in vitro rescued the NK cell-associated functional defects. In conclusion, familial HLH type 5 is associated with a spectrum of clinical symptoms, which may be a reflection of impaired expression and function of Munc18-2 also in cells other than cytotoxic lymphocytes. Mutations in STXBP2 should thus also be considered in patients with clinical manifestations other than those typically associated with HLH.
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GAPO syndrome: a report of two siblings and a review of literature.
Pediatr Dermatol
PUBLISHED: 06-12-2010
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Growth retardation, alopecia, pseudoanodontia, optic atrophy (GAPO) syndrome is a rare autosomal recessive disorder. The molecular nature of the disease is not fully understood and is considered to be one of the ectodermal dysplasia defects. In this report, we describe clinical, histologic, and ultrastructural features in two siblings born to consanguineous parents with a brief review of the literature.
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Pegylated interferon alfa-2b plus ribavirin for the treatment of chronic hepatitis C genotype 4 in adolescents.
Ann Hepatol
PUBLISHED: 06-08-2010
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Hepatitis C is endemic in the Middle East where genotype 4 accounts for most cases. Data regarding the safety and efficacy of peginterferon plus ribavirin for the treatment of chronic hepatitis C in children and adolescents, particularly those infected with genotype 4 is limited. Aim. To evaluate the efficacy and tolerability of peginterferon alfa-2b in combination with ribavirin in adolescents chronically infected with HCV genotype 4.
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Preparation of mucoadhesive oral patches containing tetracycline hydrochloride and carvacrol for treatment of local mouth bacterial infections and candidiasis.
Sci Pharm
PUBLISHED: 04-23-2010
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The specific aim of this work was to prepare mucoadhesive patches containing tetracycline hydrochloride and carvacrol in an attempt to develop a novel oral drug delivery system for the treatment of mouth infections. The bilayered patches were prepared using ethyl cellulose as a backing layer and carbopol 934 as a matrix mucoadhesive layer. Patches were prepared with different loading amounts of tetracycline hydrochloride and carvacrol. The antimicrobial activity was assessed for the prepared patches using the disc-diffusion method against the yeast Candida albicans and five bacterial strains, including Pseudomonas aeruginosa, Escherichia coli, Bacillus cereus, Staphylococcus aureus, and Bacillus bronchispti. In this work, we highlighted the possibility of occurrence of a synergistic action between carvacrol and tetracycline. The best formulation was selected based on microbiological tests, drug release, ex-vivo mucoadhesive performance, and swelling index. Physical characteristics of the selected formulations were determined. These included pH, patch thickness, weight uniformity, content uniformity, folding endurance, and patch stability.
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Effect of water stress by Polyethylene Glycol 8000 and Sodium Chloride on germination of Ephedra alata Decne seeds.
Saudi J Biol Sci
PUBLISHED: 04-14-2010
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Ephedra alata Decne is a perennial shrub and it is a very effective sand-binder. In Saudi Arabia, the species is associated with sand dunes formation, especially the mobile, non-saline and low moisture content ones. Its geographical distribution in Saudi Arabia includes the Northern, Eastern and Central regions. The aims of this study were to determine the effects of temperature, water potential and Sodium Chloride on germination of E. alata. Seeds were collected from King Khalid Centre of Wildlife Research and Development at Thumama (80 km north east of Riyadh), Saudi Arabia. Seeds were germinated at four alternating temperature regimes (8/22; 9/23; 13/27 and 18/35 °C). Seeds were also germinated under stress of aqueous Polyethylene Glycol (PEG) solutions mixed to create water potentials of 0; -0.3; -0.6; -1.2 and -1.5 MPa. Seed were also germinated in Sodium Chloride solutions of 0, 0.05, 0.1, 0.2 and 0.3 mol l(-1). Optimum germination was attained at 13/28 °C that corresponds to temperatures prevailing during spring time. Seeds germinated in Polyethylene Glycol solutions exhibited significantly lower germination than control especially when water potential fell below -0.3 MPa. Germination was also negatively affected by 0.1 mol l(-1) Sodium Chloride solution or above. Results indicated that the germination temperature responses of the nondormant seeds synchronize the event of germination with the season when environmental conditions are more favorable for subsequent growth and seedling establishment. Germination was also sensitive to both water potential and salinity.
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Systemic antiangiogenic activity of cationic poly-L-lysine dendrimer delays tumor growth.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 02-11-2010
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This study describes the previously unreported intrinsic capacity of poly-L-lysine (PLL) sixth generation (G(6)) dendrimer molecules to exhibit systemic antiangiogenic activity that could lead to solid tumor growth arrest. The PLL-dendrimer-inhibited tubule formation of SVEC4-10 murine endothelial cells and neovascularization in the chick embryo chick chorioallantoic membrane (CAM) assay. Intravenous administration of the PLL-dendrimer molecules into C57BL/6 mice inhibited vascularisation in Matrigel plugs implanted subcutaneously. Antiangiogenic activity was further evidenced using intravital microscopy of tumors grown within dorsal skinfold window chambers. Reduced vascularization of P22 rat sarcoma implanted in the dorsal window chamber of SCID mice was observed following tail vein administration (i.v.) of the PLL dendrimers. Also, the in vivo toxicological profile of the PLL-dendrimer molecules was shown to be safe at the dose regime studied. The antiangiogenic activity of the PLL dendrimer was further shown to be associated with significant suppression of B16F10 solid tumor volume and delayed tumor growth. Enhanced apoptosis/necrosis within tumors of PLL-dendrimer-treated animals only and reduction in the number of CD31 positive cells were observed in comparison to protamine treatment. This study suggests that PLL-dendrimer molecules can exhibit a systemic antiangiogenic activity that may be used for therapy of solid tumors, and in combination with their capacity to carry other therapeutic or diagnostic agents may potentially offer capabilities for the design of theranostic systems.
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Molecular identification of Probolocoryphe uca (Sarkisian, 1957; Digenea: Microphallidae) from Kuwait Bay using ITS1 and ITS2 sequences.
Parasitol. Res.
PUBLISHED: 01-19-2010
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Probolocoryphe species occur primarily as intestinal parasites of birds and mammals. Infection of the crab Nanosesarma minutum with the metacercarial cyst stages of Probolocoryphe uca is common in Kuwait Bay. In this study, the snail Cerithidea cingulata was used to determine if it would serve as first intermediate host in the parasites life cycle. To determine the snail-crab link in the life cycle of P. uca based on rDNA molecular data, ribosomal internal transcribed spacer (ITS) regions of the metacercarial cyst stage from the crab N. minutum and the sporocyst stage from the snail C. cingulata were sequenced and compared. Sequence alignment clearly demonstrated that the sporocysts and metacercariae belonged to P. uca. Comparisons were also made between the ITS sequences of P. uca and other digenean species available in GenBank. NCBI databases were used for sequence homology analysis using BLAST, ClustalW, and MUSCLE. The phylogenetic trees based on the homology analysis of the ITS (1 and 2) sequences constructed using PHYLIP and MEGA 4.0 confirmed the identification and positioned P. uca in the Microphallidae family.
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Tumor targeting of functionalized quantum dot-liposome hybrids by intravenous administration.
Mol. Pharm.
PUBLISHED: 09-01-2009
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A strategy to target functionalized quantum dot-liposome (f-QD-L) hybrid vesicles in the solid tumor tissue of tumor-bearing mice is explored. Functionalized polyethylene glycol (PEG)-lipid coated QD (f-QD) were encapsulated into the aqueous core of 100 nm cationic (DOPC:Chol: DOTAP); sterically stabilized, fluid-phase (DOPC:Chol:DSPE-PEG2000); and sterically stabilized, gel-phase (DSPC:Chol:DSPE-PEG2000) liposome vesicles. Double tracking of f-QD-L in blood was performed at different time points after intravenous administration in B16F10 melanoma tumor-bearing C57BL6 mice. Cholesteryl [-1-14C] oleate lipids probed the vesicle membrane were followed by liquid scintillation counting while QD were determined independently by elemental (Cd2+) analysis using inductively coupled plasma mass spectrometry (ICP-MS). Rapid blood clearance was observed following intravenous administration of the cationic hybrid vesicles, while incorporation of PEG at the surface of zwitterionic vesicles dramatically prolonged their blood circulation half-life after systemic administration. The "rigid" PEGylated f-QD-L (DSPC:Chol:DSPE-PEG2000) hybrid vesicles led to rapid tumor accumulation of peak values (approximately 5% of injected dose per gram tissue) of QD compared to long-circulating f-QD that accumulated in the tumor tissue at longer time points. More interestingly, this hybrid vesicle tumor retention persisted for at least 24 h. For almost all types of systems, a preferential cadmium uptake by liver and spleen was obtained. Overall, f-QD-L hybrid vesicles offer great potential for tumor imaging applications due to their rapid accumulation and prolonged retention within the tumor. Furthermore, f-QD-L offer many opportunities for the development of combinatory therapeutic and imaging (theranostic) modalities by incorporating both drug molecules and QD within the different compartments of a single vesicle.
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Blood circulation and tissue biodistribution of lipid--quantum dot (L-QD) hybrid vesicles intravenously administered in mice.
Bioconjug. Chem.
PUBLISHED: 08-07-2009
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The present work describes the pharmacokinetics of recently developed liposome-quantum dot (L-QD) hybrid vesicles in nude mice following systemic administration. Hydrophobic QD were incorporated into different bilayer compositions, and the serum stability of such hybrid vesicles was evaluated using turbidity and carboxyfluorescein release measurements. L-QD hybrid blood profile and organ biodistribution were also determined by elemental (cadmium) analysis. Following intravenous administration, different tissue biodistribution profiles and tissue affinities were observed depending on the L-QD lipid bilayer characteristics. Immediate blood clearance was observed with cationic (DOTAP/DOPE/Chol) hybrid with rapid lung accumulation, while incorporation of PEG at the surface of zwitterionic vesicles dramatically prolonged their blood circulation half-life after systemic administration. Overall, the L-QD hybrid vesicle system is considered a viable platform that allows QD delivery to different tissues through facile modulation of the hybrid vesicle characteristics. In addition, L-QD offers many opportunities for the development of combinatory therapeutic and imaging (theranostic) modalities by incorporating both drug molecules and QD within the different compartments of a single vesicle.
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Process modeling and analysis of pulp mill-based integrated biorefinery with hemicellulose pre-extraction for ethanol production: a comparative study.
Bioresour. Technol.
PUBLISHED: 07-06-2009
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Pulp and paper mills represent a major platform to use more effectively an abundant, renewable bio-resource - wood. Modification of the modern day pulp mills into integrated forest biorefineries (IFBR) presents an excellent opportunity to produce, in addition to valuable cellulose fiber, co-products including fuel grade ethanol and additional energy, thus resulting in increased revenue streams and profitability and potentially lower the greenhouse gas emissions. A process model to simulate the integrate forest biorefinery manufacturing pulp and other co-products has been developed. This model has been used to compare three integrated biorefinery scenarios: the conventional Kraft pulping process, the pulp mill-based IFBR with hemicelluloses extraction prior to pulping for ethanol production, and the pulp mill-based IFBR with both pre-extracted hemicelluloses and the short fiber for ethanol production. Based on a fixed feedstock throughput of 2000 dry Mg wood/day, results show that the pulp mill-based IFBR with both pre-extracted hemicelluloses and the short fiber cellulose converted to ethanol can produce 0.038 MM m(3) (10.04 MM gal) ethanol per year at a minimum ethanol selling price (MESP) of $491/m(3) ($1.86/gal). The economic feasibility of IFBR can be further improved by using further improvements in the pre-extraction process, other biomass such as corn stover for producing ethanol, and taking advantage of the economies of scale.
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Adrenal myelolipoma a rare benign tumour managed laparoscopically: Report of two cases.
J Minim Access Surg
PUBLISHED: 06-01-2009
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Adrenal Myelolipoma is a rare benign neoplasm composed of mature adipose tissue and a variable amount of haemopoietic elements. Most lesions are small and asymptomatic, discovered incidentally during autopsy or on imaging studies performed for other reasons. Two cases of myelolipoma are presented here, where the tumours were hormonally inactive, but presented with abdominal symptoms and were managed by laparoscopic adrenalectomy.
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Neuromuscular electrical stimulation of the gluteus medius improves the gait of children with cerebral palsy.
NeuroRehabilitation
PUBLISHED: 05-22-2009
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Neuromuscular electrical stimulation (NMES) of the gluteus medius muscles using a surface electrode during functional walking training has never been reported as a management option to improve gait in spastic diplegic children.
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Cerebellar mass as a primary presentation of papillary thyroid carcinoma: case report and literature review.
Head Neck Oncol
PUBLISHED: 04-15-2009
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Papillary carcinoma is the most common differentiated malignant thyroid neoplasm. The biological course of this cancer is typically indolent with a protracted clinical course. Metastases commonly occur in regional lymph nodes, and distant metastasis is a late and rare occurrence. We report a patient who presented with cerebellar metastasis prior to the diagnosis of papillary thyroid carcinoma and review the literature of brain metastasis from papillary thyroid carcinoma.
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Skin and environmental contamination with vancomycin-resistant Enterococci in patients receiving oral metronidazole or oral vancomycin treatment for Clostridium difficile-associated disease.
Infect Control Hosp Epidemiol
PUBLISHED: 02-07-2009
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Oral metronidazole has been recommended for treatment of mild-to-moderate Clostridium difficile-associated disease (CDAD), in part because of concern that use of vancomycin may be more likely to promote colonization and transmission of vancomycin-resistant enterococci (VRE). The objective of our study was to compare the frequency of skin and environmental VRE contamination associated with metronidazole treatment for CDAD with such frequency associated with vancomycin treatment for CDAD.
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Community onsite treatment of cold strong sewage in a UASB-septic tank.
Bioresour. Technol.
PUBLISHED: 01-13-2009
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Two community onsite UASB-septic tanks namely R1 and R2 were operated under two different HRT (2 days for R1 and 4 days for R2) in parallel over a year and monitored over the cold half of the year. During the monitoring period, the sewage was characterised by a high COD(tot) of 905mg/l with a high fraction of COD(ss), viz. about 43.7%, and rather low temperature of 17.3 degrees C. The achieved removal efficiencies in R1 and R2 for COD(tot), COD(sus), COD(col), COD(dis), BOD(5) and TSS were "51%, 83%, 20%, 24%, 45% and 74%" and "54%, 87%, 10%, 28%, 49% and 78%", respectively. The difference in the removal efficiencies of those parameters in R1 and R2 is marginal and was only significant (p<0.05) for COD(sus). The sludge filling period of the reactors is expected to be 4-7 years. In view of that, the UASB-septic tank system is a robust and compact system as it can be adequately designed in Palestine at 2 days HRT.
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Complications in paediatric liver transplant from Kuwait when transplanted abroad.
Arab J Gastroenterol
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Since the introduction of liver transplantation (LTx) in children suffering from liver failure in 1963, many centres around the world have offered this service to children that have no other alternative. The aim of this retrospective study is to analyse the results of paediatric liver transplant in Kuwait over the last decade.
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Marfan Syndrome: Correct diagnosis can save lives.
Sultan Qaboos Univ Med J
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Marfan syndrome is a heritable disorder of the connective tissue that affects many systems of the body. However, the most serious complication in patients with Marfan syndrome is progressive enlargement of the aortic root, which may lead to aortic dissection, rupture, or aortic regurgitation. Prevention of these life threatening complications is very important in the management of this condition. A 39-year-old Omani man presented with progressive shortness of breath and eventually underwent major but successful cardiac surgery. It is very important to recognise Marfan syndrome early as preventive actions are possible if the condition is diagnosed before complications occur.
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The validity of different display monitors in the assessment of dental implant site dimensions in cone beam computed tomography images.
Acta Odontol. Scand.
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To determine if the differing contrast resolution of various LCD monitors affects the reliability or accuracy of measurements of proposed implant sites.
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The effect of artificial lipid envelopment of Adenovirus 5 (Ad5) on liver de-targeting and hepatotoxicity.
Biomaterials
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Human Adenovirus type 5 (Ad5) has been extensively explored in clinical gene therapy, but its immunogenicity dramatically affects the kinetics and toxicity profile of the vector. We previously designed a variety of artificial lipid bilayer envelopes around the viral capsid to develop safer hybrid vectors. Here, we studied the interaction of enveloped Ad in cationic (DOTAP:Chol) or anionic (DOPE:CHEMS) lipid bilayers with different blood components. When Ad was enveloped by cationic lipids, significantly high levels of viral uptake in HepG2 cultured cells were achieved, independent of blood coagulation factors present. In vitro experiments also showed that artificial envelopment of Ad completely altered the affinity towards both human and murine red blood cells. After intravenous administration in BALB/c mice, real-time PCR and transgene expression studies indicated that cationic lipid envelopes significantly reduced hepatocyte transduction significantly increasing virus lung accumulation compared to DOPE:CHEMS enveloped or naked Ad. ALT/AST serum levels and liver histology showed that envelopment also improved hepatotoxicity profiles compared to naked Ad. This study suggests that artificial envelopes for Ad significantly alter the interactions with blood components and can divert viral particles from their natural liver tropism resulting in reduced hepatotoxicity.
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Characterisation of organic matter associated with groundwater arsenic in reducing aquifers of southwestern Taiwan.
J. Hazard. Mater.
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Arsenic (As) in groundwaters extensively used by people across the world constitutes a serious public health threat. The importance of organic matter (OM) as an electron donor in microbially-mediated reduction of As(V) or Fe(III)-bearing As-host minerals leading to mobilisation of solid-phase arsenic is widely recognised. Notwithstanding this, there are few studies characterising OM in such aquifers and, in particular, there is a dearth of data from the classic arsenic bearing aquifers in southwestern Taiwan. Organic geochemical analyses of sediments from a known groundwater arsenic hot-spot in southwestern Taiwan revealed contributions of thermally mature and plant derived origin, consistent with OM sources in all other Asian groundwater aquifer sediments analysed to date, indicating comparable sources and routes of OM transfer. The combined results of amended As(V) reduction assays with the organic geochemical analysis revealed that the microbiological process of dissimilatory As(V) reduction is active in this aquifer, but it is not controlled by a specific source of analysed OM. These indicate that (i) part of the OM that was considered to be less bio-available could still be used as an electron donor or (ii) other electron donors, not analysed in present study, could be controlling the rate of As release.
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Lipid-peptide vesicle nanoscale hybrids for triggered drug release by mild hyperthermia in vitro and in vivo.
ACS Nano
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The present study describes leucine zipper peptide-lipid hybrid nanoscale vesicles engineered by self-assembled anchoring of the amphiphilic peptide within the lipid bilayer. These hybrid vesicles aim to combine the advantages of traditional temperature-sensitive liposomes (TSL) with the dissociative, unfolding properties of a temperature-sensitive peptide to optimize drug release under mild hyperthermia, while improving in vivo drug retention. The secondary structure of the peptide and its thermal responsiveness after anchoring onto liposomes were studied with circular dichroism. In addition, the lipid-peptide vesicles (Lp-peptide) showed a reduction in bilayer fluidity at the inner core, as observed with DPH anisotropy studies, while the opposite effect was observed with an ANS probe, indicating peptide interactions with both the headgroup region and the hydrophobic core. A model drug molecule, doxorubicin, was successfully encapsulated in the Lp-peptide vesicles at higher than 90% efficiency following the remote loading, pH-gradient methodology. The release of doxorubicin from Lp-peptide hybrids in vitro indicated superior serum stability at physiological temperatures compared to lysolipid-containing temperature-sensitive liposomes (LTSL) without affecting the overall thermo-responsive nature of the vesicles at 42 °C. A similar stabilizing effect was observed in vivo after intravenous administration of the Lp-peptide vesicles by measuring (14)C-doxorubicin blood kinetics that also led to increased tumor accumulation after 24 h. We conclude that Lp-peptide hybrid vesicles present a promising new class of TSL that can offer previously unexplored opportunities for the development of clinically relevant mild hyperthermia-triggered therapeutic modalities.
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Liposome-gold nanorod hybrids for high-resolution visualization deep in tissues.
J. Am. Chem. Soc.
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The design of liposome-nanoparticle hybrids offers a rich toolbox for the fabrication of multifunctional modalities. A self-assembled liposome-gold nanorod hybrid vesicular system that consists of lipid-bilayer-associated gold nanorods designed to allow deep tissue detection, therapy, and monitoring in living animals using multispectral optoacoustic tomography has been fabricated and characterized in vitro and in vivo.
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Comparison of central corneal thickness measurements using ultrasound pachymetry, ultrasound biomicroscopy, and the Artemis-2 VHF scanner in normal eyes.
Clin Ophthalmol
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To compare the precision of central corneal thickness (CCT) measurements taken with the handheld ultrasound pachymeter (USP), ultrasound biomicroscopy (UBM), and the Artemis-2 very high frequency ultrasound scanner (VHFUS) on normal subjects.
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The prescription of allopurinol in a tertiary care centre: appropriate indications and dose adjustment.
Clin Med Insights Arthritis Musculoskelet Disord
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To determine the appropriateness (both indications and adequate dosage regimen via creatinine clearance estimation) of allopurinol by physicians of different specialties in a tertiary care centre.
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Degree of chemical functionalization of carbon nanotubes determines tissue distribution and excretion profile.
Angew. Chem. Int. Ed. Engl.
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Getting rid of the tubes: An assessment of the retention of functionalized multi-walled carbon nanotubes (MWNTs) in the organs of mice was carried out using single photon emission computed tomography and quantitative scintigraphy (see scheme). Increasing the degree of functionalization on MWNTs enhanced renal clearance, while lower functionalization promoted reticuloendethelial system accumulation.
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The impact of variation in access to care on the management of Hirschsprung disease.
J. Pediatr. Surg.
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Variation in access to care has a significant impact on the disease management process and outcomes. Variable access to care might have similar effects on the management of Hirschsprung disease (HD). However, such variation has not been highlighted.
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Pharmacokinetics & tissue distribution of temperature-sensitive liposomal doxorubicin in tumor-bearing mice triggered with mild hyperthermia.
Biomaterials
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Drug-loaded temperature-sensitive liposomes (TSL) in combination with hyperthermia (HT) have attracted considerable attention for cancer treatment. Different TSL systems have been designed with wide variations in their temperature sensitivity and drug release profile. Low temperature-sensitive liposomes (LTSL) with the capacity for ultrafast drug release, traditional temperature-sensitive (TTSL) with intermediate drug release properties and non-temperature-sensitive liposomes (NTSL) (no drug release) were dual-labeled with (3)H-cholesteryl hexadecyl ether ((3)H-CHE) lipid and loaded with (14)C-doxorubicin ((14)C-Dox). Their blood profile, serum stability, tissue distribution and tumor localization (B16F10 melanoma) were studied after intravenous administration and mild HT treatment. LTSL showed higher affinity for the liver compared to TTSL and NTSL which were uptaken mainly by spleen. Under normal conditions (no HT) Dox leakage from liposomes was expected, higher for LTSL, less for TTSL and minimal for NTSL. Localized HT did not affect the overall blood circulation or organ accumulation for all TSL studied. Since LTSL showed ultrafast Dox release kinetics at 42 °C, the highest drug accumulation in tumors was observed using this system immediately after HT, however decreased significantly after 24 h. In contrast, TTSL and NTSL showed 2-3 fold increase in both liposome and Dox levels that indicated enhanced tumor extravasation of intact Dox-loaded liposomes during the 60 min HT applications. More interestingly, high levels of drug tumor accumulation were achieved 24 h post-HT. This study offers further understanding on how the mechanisms of drug release from temperature-sensitive liposomes affect their pharmacological profile under mild hyperthermia.
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