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Find video protocols related to scientific articles indexed in Pubmed.
Design and synthesis of novel thiophenes bearing biologically active aniline, aminopyridine, benzylamine, nicotinamide, pyrimidine and triazolopyrimidine moieties searching for cytotoxic agents.
Acta Pol Pharm
PUBLISHED: 10-01-2014
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To discover new bioactive lead compounds for medicinal purposes, herein, (E)-3-(substituted amino)-1-thiophen-2-yl-prop-2-en-1-ones 3-8, aminopyridines 9-11, benzylamine 12, nicotinamide 13, pyrimidines 14, 15, hexanoic acid 16 and triazolopyrimidine 19 were prepared and tested for cytotoxic activity. Results showed that the tested compounds exhibited a remarkable activity, especially compounds 3 and 19 with IC50 values (55.2 and 50.49 microM, respectively) compared to doxorubicin (IC50 = 71.8 microM) as a reference drug.
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Immunohistochemical Expression of MCM2 in Nonmelanoma Epithelial Skin Cancers.
Am J Dermatopathol
PUBLISHED: 06-18-2014
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: Cutaneous basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) represent 45.5% and 37.02%, respectively, of total malignant skin cancer according to the latest registry of Egyptian National Cancer Institute. Minichromosome maintenance (MCM) proteins are essential replication initiation factors. The current study examined the immunohistochemical expression of MCM2 in normal skin (10 cases), some proliferative skin lesions (6 psoriasis, 2 keratoacanthoma, and 2 seborrheic keratosis), and nonmelanoma epithelial skin cancers (20 BCC and 21 SCC). MCM2 was expressed in basal layer of normal epidermis and upregulated in proliferative skin lesions and nonmelanoma epithelial skin cancers without significant differences between the latter groups (P > 0.05). Mean and median values of MCM2 percentage of expression in BCC were higher than that of SCC (P = 0.004). MCM2 promotes proliferative capacity of the cells manifested by its expression in basal layer of epidermis, hyperproliferative skin lesions, and malignant cutaneous tumors. Proliferative capacity of BCC may be higher than SCC and this does not necessarily reflect aggressive behavior.
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Screening for ADHD in a Sample of Egyptian Adolescent School Students.
J Atten Disord
PUBLISHED: 06-04-2014
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To screen for ADHD in a sample of Egyptian adolescent students, and study the distribution of different subtypes of ADHD, associated comorbidities, and sociodemographic correlates.
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Soluble adhesion molecules as markers of native arteriovenous fistula thrombosis in children on uremia.
Blood Coagul. Fibrinolysis
PUBLISHED: 05-09-2014
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Vascular access represents a lifeline for children undergoing hemodialysis. A failure of vascular access among patients receiving regular hemodialysis is associated with increased morbidity, mortality and costs. We assessed the possibility of using soluble adhesion molecules as reliable predictors of vascular access failure in children on hemodialysis. Moreover, we evaluated whether there is an association among the different studied adhesion molecules in hemodialysis patients with thrombosed and non-thrombosed arteriovenous fistula fistulas (AVFs). This study included 55 hemodialysis children, 36 with good access and 19 with access failure, and 20 healthy volunteers. Forty-four patients had native AVFs and 11 patients had tunneled permanent catheter (11with thrombosed and 33 with non-thrombosed AVFs). Serum-soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin) and soluble P-selectin (sP-selectin) were measured using ELISA technique. A significant increase was found in the levels of sVCAM-1, sICAM-1, sE-selectin and sP-selectin versus controls and all hemodialysis patients, hemodialysis patients with good access and hemodialysis patients with access failure (P=0.001 for sVCAM-1 and sICAM-1 and P=0.0001 for sE-selectin and sP-selectin). A significant increase was found in the levels of sVCAM-1, sE-selectin and sP-selectin in both chronic hemodialysis patients with thrombosed and non-thrombosed native AVFs versus controls (P=0.0001 for all parameters). There was significant difference between both chronic hemodialysis patients with thrombosed and non-thrombosed native AVFs as regard to sVCAM-1 (54.64±30.82 versus 25.69±27.96ng/ml, P=0.04). Both sICAM-1 and sP-selectin were positively correlated with the erythropoietin (EPO) dose in hemodialysis children (r=0.31, P=0.04 and r=0.32, P=0.04, respectively). A significant positive association was found between E-selectin and sP-selectin in hemodialysis patients with thrombosed AVFs (r=0.83, P=0.04). There was a significant correlation between sVCAM-1 and EPO dose in thrombosed AVF group (r=0.84, P=0.01). The assessment of serum sVCAM-1 might be useful for the identification of the chronic hemodialysis patients at an increased risk for native AVFs thrombosis. The role of EPO in vascular access failure should be taken into consideration. The clinical relevance of these observations warrants further investigations.
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Influence of alendronate administration regimen on the final outcome of implant osseointegration in an osteoporotic model.
J Int Acad Periodontol
PUBLISHED: 04-10-2014
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This study aimed to evaluate the bone response around titanium implants in osteoporotic rabbits receiving oral alendronate (ALN) for one month either simultaneously with implant placement (IP) or stopped immediately before surgery. Six weeks before IP, 34 adult female New Zealand white rabbits were submitted to intramuscular injections of dexamethasone (3 mg/kg twice a week) to induce osteoporosis-like conditions. Two animals were sacrificed and histological examinations of their leg bones were performed to confirm the osteoporosis-like condition, as compared to a healthy animal. The remaining 32 rabbits were then divided into four equal groups. Group I represented osteoporosis-like animals receiving implants. For Groups II, III and IV, osteoporosis-like animals received calcium phosphate cement before IP. Animals in Group II received implants without any systemic treatment for osteoporosis. In Group III, ALN was simultaneously started with IFP. In Group IV, ALN was stopped immediately before surgery. At 12 weeks post-surgery all animals were sacrificed. Both bone-implant interface and mineralized bone area percentage (MBA%) were microscopically evaluated. Group IV showed a significant gain in MBA% (p < 0.05), along with the most favorable implant integration outcome. Our results suggest that finishing an ALN course before implant placement could enhance the healing capacity around implants.
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Potential use of niosomal hydrogel as an ocular delivery system for atenolol.
Biol. Pharm. Bull.
PUBLISHED: 04-04-2014
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Niosomes have been reported as possible approach to improve the low corneal penetration and bioavailability characteristics for many drugs. The purpose of this study was to prepare and characterize an effective ocular niosomal hydrogel containing 0.5% (w/v) atenolol which is ?1 adrenoceptor blocker for treatment of glaucoma. Thin film hydration method was used for the preparation of niosomes using Span 60 and cholesterol at different molar ratios. Niosomes were characterized using laser diffraction particle size analyzer, transmission electron microscopy, and differential scanning calorimetry. The results showed that higher entrapment efficiency (80.7%±1.2) was obtained from niosomes prepared using Span 60/cholesterol at a 2 : 1 molar ratio. Stability study revealed that a fairly high retention of atenolol inside vesicles (83.1%±2.35) up to a period of 3 months at 4°C. It was found that niosomal hydrogel formulation using carbopol 934P significantly exhibited sustained in vitro release of the drug compared with free drug solution and other polymeric hydrogels. The intraocular pressure (IOP) lowering activity of selected atenolol formulations was determined and compared with that of atenolol solution. It is worth noting that niosomal hydrogel formulation was found to show the most significant prolonged decrease in IOP, suggesting that niosomal hydrogel could be a promising delivery system for atenolol.
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Broadband ultraviolet A in the treatment of psoriasis vulgaris: a randomized controlled trial.
Int. J. Dermatol.
PUBLISHED: 04-02-2014
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Broadband ultraviolet A (BB-UVA) has been successfully used in the treatment of scleroderma, a UVA1-responsive dermatosis.
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Some variables affecting the characteristics of Eudragit E-sodium alginate polyelectrolyte complex as a tablet matrix for diltiazem hydrochloride.
Acta Pharm
PUBLISHED: 03-28-2014
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Eudragit E (EE)-sodium alginate (SA) polyelectrolyte complexes (PECs) were prepared at pH 4 and 5.8 using sodium alginate of high (SAH) and low viscosity (SAL). The optimum EE-SA complexation mass ratio was determined using viscosity measurements. Interactions between EE and SA in PECs were characterized by Fourier transform infra-red spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Diltiazem hydrochloride (DTZ HCl) tablets were prepared using the prepared EE-SA PECs and their physical mixtures at different ratios as matrices. Tablets were evaluated for swelling characteristics and in vitro drug release. Tablets containing EE-SAH physical mixtures of ratios (1.5:1 and 1:3) as matrices were effective in achieving sustained release of DTZ HCl, where the percent drug released was significantly (p < 0.05) decreased compared to that from tablets either containing the same ratios of EE-SAL physical mixtures or the preformed EE- -SAH and EE-SAL PECs.
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Synthesis, characterization and anti-breast cancer activity of new 4-aminoantipyrine-based heterocycles.
Int J Mol Sci
PUBLISHED: 03-19-2014
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4-Aminoantipyrine was utilized as key intermediate for the synthesis of pyrazolone derivatives bearing biologically active moieties. The newly synthesized compounds were characterized by IR, 1H- and 13C-NMR spectral and microanalytical studies. The compounds were screened as anticancer agents against a human tumor breast cancer cell line MCF7, and the results showed that (Z)-4-((3-amino-5-imino-1-phenyl-1H-pyrazol-4(5H)-ylidene)methylamino)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 5, 3-(4-bromophenyl) -1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 13, 1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-3-(4-iodophenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 14, 3,3'-(4,4'-sulfonylbis(4,1-phenylene))bis(1-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile) 16, (Z)-1- (1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-2-hydrazono-4-oxo-3-phenyl-1,2,3,4-tetrahydropyrimidine-5-carbonitrile 17, (Z)-1-(1,5-dimethyl-3-oxo-2-phenyl- 2,3-dihydro-1H-pyrazol-4-yl)-4-oxo-3-phenyl-2-(2-phenylhydrazono)-1,2,3,4-tetrahydro pyrimidine-5-carbonitrile 18, and (Z)-4-(3-amino-6-hydrazono-7-phenyl-6,7-dihydro pyrazolo[3,4-d]pyrimidin-5-yl)-1,5-dimethyl-2-phenyl-1,2-dihydropyrazol-3-one 19 were the most active compounds with IC50 values ranging from 30.68 to 60.72 µM compared with Doxorubicin as positive control with the IC50 value 71.8 µM.
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Cognitive functions in euthymic Egyptian patients with bipolar disorder: are they different from healthy controls?
J Affect Disord
PUBLISHED: 02-23-2014
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There is marked interest to research neurocognitive functions in bipolar disorder during euthymia. Consequently we aimed to study cognitive functions in euthymic bipolar patients and factors affecting them.
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Synthesis and anti-breast cancer evaluation of novel N-(guanidinyl)benzenesulfonamides.
Int J Mol Sci
PUBLISHED: 02-23-2014
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A series of 4-(substituted)-N-(guanidinyl)benzenesulfonamides bearing biologically active pyrazole, pyrimidine and pyridine moieties were prepared and evaluated for their anticancer activity against human tumor breast cell line (MCF7). These sulfonamides showed promising activity with IC50 values ranging from 49.5 to 70.2 ?M. The structure-activity relationship of the synthesized compounds was studied. Interestingly, it was found that the most potent compounds in this study were the corresponding 2-cyanoacrylate 3, 3-oxobutanoate 4, pyrazole 6, pyridine 9 and pyrazole 13. Compounds 7 and 8 are nearly as active as Doxorubicin as reference drug with (IC50 values=70.2, 68.1 ?M), while compounds 5, 10 and 11 exhibited a moderate activity.
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Oxidant-antioxidant status in Egyptian children with sickle cell anemia: a single center based study.
J Pediatr (Rio J)
PUBLISHED: 02-05-2014
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the present study was conducted to investigate the oxidant-antioxidant status in Egyptian children with sickle cell anemia.
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Dyserythropoiesis in a child with pyruvate kinase deficiency and coexistent unilateral multicystic dysplastic kidney.
Pediatr Blood Cancer
PUBLISHED: 01-30-2014
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Pyruvate kinase (PK) deficiency is the commonest enzyme deficiency in the glycolytic pathway leading to hemolytic anemia secondary to decreased Adenosine Triphosphate (ATP) synthesis in the red cells. synthesis. PK deficiency due to mutations in the PKLR (1q21) gene leads to highly variable clinical presentation ranging from severe fetal anemia to well compensated anemia in adults. We describe dyserythropoiesis in the bone marrow of a child with transfusion dependent anemia and unilateral multicystic dysplastic kidney (MCDK) mimicking Congenital Dyserythropoietic Anemia type I (CDA type I). Persistently low erythrocyte PK levels and double heterozygous mutations present in the PKLR gene confirmed the diagnosis of PK deficiency.
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Renal cell carcinoma with rhabdoid and sarcomatoid features presented as a metastatic thigh mass with an unusual immunohistochemical profile.
Rare Tumors
PUBLISHED: 01-23-2014
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Renal cell carcinoma (RCC) may metastasize anywhere in the body and sometimes the primary tumor is missing and necessitates extensive investigations to detect. In this report, we describe a case of RCC metastasizing to the thigh in a 70 year old male with a highly pleomorphic morphology suggesting a high grade sarcoma that showed unequivocal positivity for desmin directing the diagnosis for pleomorphic rhabdomyosarcoma. After completion of 33 cycles of radiotherapy, the patient developed large intraabdominal mass that showed conventional areas of RCC with immunoreactivity for CD10, CK, EMA, carbonic anhydrase IX and vimentin. The tumor cells in other areas resembled that of thigh mass which raised suspicions whether the two masses represented the same tumor or not. Surprisingly, the tumor cells of thigh mass showed diffuse positivity for CD10 and focal expression for CK, EMA and carbonic anhydrase IX. Extensive investigations failed to detect any primary renal lesions. The present case demonstrated that RCC can metastasize to virtually any body site and can have significant morphologic overlap with other non-renal neoplasms. Absence of primary origin of RCC according to radiological and operative data should not hinder the diagnosis of metastatic RCC. RCC with sarcomatoid and rhabdoid features carries aggressive behavior manifested by great metastatic potential and short survival time.
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Study of thyroid function in Egyptian children with ?-thalassemia major and ?-thalassemia intermedia.
J Egypt Public Health Assoc
PUBLISHED: 12-31-2013
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Thyroid dysfunction is a known complication of transfusion-dependent ?-thalassemia. However, information on its frequency and risk factors among Egyptian Children is still unclear.
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Cell-free DNA concentration and integrity as a screening tool for cancer.
Indian J Cancer
PUBLISHED: 09-25-2013
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This study aims to evaluate cell-free DNA (CFDNA) concentration and integrity in patients with malignant and nonmalignant diseases and in controls to investigate their value as a screening test for cancer, and to correlate them with clinicopathological parameters of cancer patients.
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BB-UVA vs. NB-UVB in the treatment of vitiligo: a randomized controlled clinical study (single blinded).
Photodermatol Photoimmunol Photomed
PUBLISHED: 07-04-2013
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Vitiligo is an acquired pigmentary disorder that affects between 1% and 2% of the general population. Phototherapy remains the cornerstone of treatment, with NB-UVB being the most frequently used. BB-UVA can be a plausible alternative for darker population; skin photo type III and IV.
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Excision repair cross-complementing group 2/Xeroderma pigmentousm complementation group D (ERCC2/XPD) genetic variations and susceptibility to diffuse large B cell lymphoma in Egypt.
Int. J. Hematol.
PUBLISHED: 06-19-2013
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Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous neoplasm. Although several genetic and environmental factors have been postulated, no obvious risk factors have been emerged for DLBCL in the general population. DNA repair systems are responsible for maintaining the integrity of the genome and protecting it against genetic alterations that can lead to malignant transformation. The current study aimed at investigating the possible role of ERCC2/XPD Arg156Arg, Asp312Asn and Lys751Gln genetic polymorphisms as risk factors for DLBCL in Egypt. The study included 81 DLBCL patients and 100 healthy controls. Genotyping of the studied genetic polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism technique. Our results revealed that there was no statistical difference encountered in the distribution of -Asp312Asn and -Lys751Gln polymorphic genotypes between DLBCL cases and controls, thus it could not considered as molecular risk factors for DLBCL in Egyptians. However, Arg156Arg polymorphism at exon-6 conferred twofold increased risk of DLBCL (OR 2.034, 95 %CI 1.015-4.35, p = 0.43), and the risk increased when co-inherited with Lys751Gln at exon-23 (OR 3.304, 95 %CI 1.113-9.812, p = 0.038). In conclusion, ERCC2/XPD Arg156Arg polymorphism might be considered as a genetic risk factor for DLBCL in Egyptians, whether alone or conjoined with Lys751Gln.
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Skin tags: a link between lesional mast cell count/tryptase expression and obesity and dyslipidemia.
Indian J Dermatol
PUBLISHED: 06-01-2013
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The etiology of skin tags (STs) is not fully understood. A relation to diabetes mellitus and obesity was suggested. Few studies of possible mast cells (MCs) involvement were reported. Tyrptase is a mast cell mediator and a potent fibroblast growth factor. It may provide a molecular link between mast cell activation and fibrosis.
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Endothelin-1 and its a and B receptors: are they possibly involved in vitiligo?
Acta Dermatovenerol Croat
PUBLISHED: 05-21-2013
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Endothelin-1 (ET-1), expressed by keratinocytes, has paracrine effects on melanocytes. The endothelin 1-axis [ET-1, endothelin A receptor (ETAR) and endothelin B receptor (ETBR)] is thought to play a role in the depigmentation process occurring in vitiligo, with no studies on the cutaneous protein expression of this axis in the disease. The aim of the present study was to compare the expression of ET-1 axis in lesional and perilesional normal epidermis of vitiligo patients with healthy controls. Ten patients with non-segmental stable vitiligo and ten healthy controls were included. Skin biopsies from all subjects were studied immunohistochemically for ET-1, ETAR and ETBR expression. No significant difference was detected in the rate of expression and the degree of staining of ET-1 axis in controls compared with each of lesional vitiligo and perilesional normal epidermis (P>0.05). There was no statistically significant difference between lesional vitiligo and perilesional normal epidermis regarding to the rates of ET-1, ETAR and ETBR expression (P=0.82, P=0.5 and P=0.99, respectively). Semi-quantitative analysis of ETAR revealed higher staining grades in lesional compared with perilesional normal epidermis, with a statistically significant difference (P=0.04). There was no statistically significant difference between the two groups regarding the staining grades of ET-1 and ETBR (P>0.05 for both markers). A highly significant positive correlation was found between ET-1 and ETAR (r =0.99, P<0.05) and between ET-1 and ETBR (r=0.87, P<0.05). The study demonstrated unaltered expression of ET-1 axis in keratinocytes in lesional vitiligo and perilesional normal epidermis. Additional studies on the differential expression of this axis in keratinocytes and melanocytes are therefore required.
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Premaxillary characteristics in complete bilateral cleft lip and palate: A predictor for treatment outcome.
Ann Maxillofac Surg
PUBLISHED: 05-11-2013
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The aim of the current study was to investigate how bilateral cleft lip and palate (BCLP) cases responded differently to presurgical orthopedics (PSO) and primary lip repair (LR) based on premaxillary characteristics. We suggest a clinically oriented descriptive classification for BCLP based on premaxillary characteristics.
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Highly reproducible SERS detection in sequential injection analysis: real time preparation and application of photo-reduced silver substrate in a moving flow-cell.
Talanta
PUBLISHED: 04-26-2013
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This paper reports an improved way for performing highly reproducible surface enhanced Raman scattering of different analytes using an automated flow system. The method uses a confocal Raman microscope to prepare SERS active silver spots on the window of a flow cell by photo-reduction of silver nitrate in the presence of citrate. Placement of the flow cell on an automated x and y stages of the Raman microscope allows to prepare a fresh spot for every new measurement. This procedure thus efficiently avoids any carry over effects which might result from adsorption of the analyte on the SERS active material and enables highly reproducible SERS measurements. For reproducible liquid handling the used sequential injection analysis system as well as the Raman microscope was operated by the flexible LabVIEW based software ATLAS developed in our group. Quantitative aspects were investigated using Cu(PAR)2 as a model analyte. Concentration down to 5×10(-6) M provided clear SERS spectra, a linear concentration dependence of the SERS intensities at 1333 cm(-1) was obtained from 5×10(-5) to 1×10(-3) with a correlation coefficient r=0.999. The coefficient of variation of the method Vxo was found to be 5.6% and the calculated limit of detection 1.7×10(-5) M. The results demonstrate the potential of SERS spectroscopy to be used as a molecular specific detector in aqueous flow systems.
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Circulating soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) as diagnostic and prognostic marker in neonatal sepsis.
Cytokine
PUBLISHED: 04-03-2013
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Triggering receptor expressed on myeloid cells-1 (TREM-1) is an important receptor involved in the innate inflammatory response and sepsis. We assessed soluble TREM-1 (sTREM-1) in 112 septic neonates (63 culture-positive and 49 culture-negative) and 40 healthy controls as a potential early diagnostic and prognostic marker for neonatal sepsis (NS).
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Air samplings in a Campylobacter jejuni positive laying hen flock.
Ann Agric Environ Med
PUBLISHED: 04-02-2013
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The air in laying hen houses contains high concentrations of airborne bacteria. The numbers of these bacteria can be influenced by the efficiency of the chosen sampling method. In the presented study, AGI-30 Impingers and the Coriolis(®)µ air Sampler were compared in terms of their efficiency in sampling aerobic mesophilic bacteria in a laying hen house. Measurements were conducted in a laying hen flock with high prevalences of C. jejuni in order to investigate if culturable cells of this organism can also be detected by the applied methods. Airborne dust was also analyzed for the presence of C. jejuni specific DNA to assess the possible occurrence of non-culturable C. jejuni in the hen house air. The numbers of mesophilic airborne bacteria ranged from 8 × 10(4) - 2 × 10(6) CFU/m(-3) when sampled using AGI-30 Impingers, and from 2 × 10(5) - 4 × 10(6) CFU/m -3 when sampled using a Coriolis(®)µ air Sampler. The concentrations detected simultaneously by both devices correlated well (rPearson = 0.755), but the Coriolis(®)µ air Sampler showed a significantly higher sampling efficiency (p<0.001). Although, the within flock prevalence of C. jejuni was high during the experiments (between 70-93%), neither of the air sampling methods could detect culturable C. jejuni from the air. However, C. jejuni specific DNA was detected in 15 out of 18 airborne dust samples by mapA PCR. Based on the results, it can be concluded that airborne culturable C. jejuni were not detectable, even with an efficient air sampler, because of their low concentration. Therefore, the risk of airborne infection to poultry workers on inhaling airborne C. jejuni seems negligible. Also, the transmission of culturable C. jejuni to neighboring farms by the airborne route is unlikely. Otherwise, the detection of airborne C. jejuni specific DNA suggests that non-culturable cells could appear in the hen house air, and in future it should be verified whether sampling stress of the air sampling methods could induce the non-culturable state.
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Thiourea derivatives incorporating a hippuric acid moiety: synthesis and evaluation of antibacterial and antifungal activities.
Eur J Med Chem
PUBLISHED: 04-01-2013
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New series of thiourea derivatives incorporating a hippuric acid moiety have been synthesized through the reaction of 4-hippuric acid isothiocyanate with various nitrogen nucleophiles such as aliphatic amines, aromatic amines, sulfa drugs, aminopyrazoles, phenylhydrazine and hydrazides. The synthesized compounds were tested against bacterial and fungal strains. Most of compounds, such as 2-(4-(3-(3-bromophenyl)thioureido)benzamido)acetic acid and 2-(4-(3-(4-(N-pyrimidin-2-ylsulfamoyl)phenyl)thioureido)benzamido)acetic acid, showed significant antibacterial and antifungal activities. These compounds comprise a new class of promising broad-spectrum antibacterial and antifungal agents.
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Synthesis and biological evaluation of bis-imidazolidineiminothiones: a comparative study.
Arch. Pharm. (Weinheim)
PUBLISHED: 03-20-2013
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A series of 15 novel symmetrical and non-symmetrical bis-imidazolidineiminothiones (6a-g, 7a-e, 8a,b, and 9) with various substituents at N-(1) (p-tolyl, p-methoxyphenyl, p-ethoxyphenyl, p-chlorophenyl, p-bromophenyl, p-iodophenyl, and 3,5-dichlorophenyl) and different linkers between the N-(3) atoms [4,4-oxybis(4,1-phenylene), 2,2-dimethoxybiphenyl, and (1,3,3-trimethylcyclohexyl)methyl)] were prepared in 65-75% yields from substituted N-arylcyanothioformanilides and various bis-isocyanates. Screening for cytotoxicity against the HEPG2, HEP2, MCF7, and HCT116 tumor cell lines gave IC50 values ranging from 6.3 to 84.6?µM, where compounds 6b,d,e,g and 7a were markedly active against a least one cell line, underlining the matching effect of properly positioned substituents on N-(1) and the appropriate N-(3)-N-(3) linker. Likewise, all heterocyles were tested against microbial organisms (Pseudomonas aeruginosa, Sarcina lutea, Bacillus pumilus, and Micrococcus luteus) and fungal strains (Candida albicans and Penicilium chrysogenum). Most compounds showed significant antibacterial and antifungal activities, reaching in certain cases the same level of antimicrobial activity as the standard antibacterial agent erythromycin and the antifungal agent metronidazole. The antimicrobial activity was further supported by quantitative assessment of susceptibilities of a selection of the preceding microorganisms using minimum inhibitory concentration and minimum bactericidal concentration techniques. Finally, the antiviral properties of all compounds were investigated against the viral strains HAV, HSV1, and CoxB4, where 6c,d,f and 7a,c,e were markedly active against one or two viral strains, reducing the virus plaque count of various viral strains by 66 to 88%. Structure activity relationship studies revealed several matching pairs of aromatic substituents on N-(1) and the N-(3)-N-(3) linkers, which could serve to optimize structural features for high activity to eventually render such compounds clinically useful drug agents.
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Free radical grafting kinetics of acrylamide onto a blend of starch/chitosan/alginate.
Carbohydr Polym
PUBLISHED: 02-21-2013
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Grafting of monomer onto polymer backbone is one of the effective and accessible methods for the chemical modification of polysaccharides. Grafting of acrylamide (AAm) onto polysaccharides blend (PsB) composed of starch, chitosan and alginate has been carried out using potassium persulfate (KPS) as an initiator. The kinetics of the grafting polymerization also has been studied. The grafting parameters have been evaluated by changing the initial concentrations of AAm from 8 to 16 g, PsB from 6 to 14 g and KPS from 0.2 to 1 g. Evidence of grafting has been obtained from FTIR, XRD and TGA. The kinetics of the grafting polymerization also has been studied. The grafting rate equation of the produced hydrogel (PsB-g-AAm) hydrogel has been expressed by: Rg=k[AAm] [PsB](0.5) [KPS](0.5). The grafting rate is a first order dependence to [AAm] initial concentration and square root to [PsB] and [KPS] initial concentrations in the used concentrations range.
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Synthesis of thiosemicarbazones derived from N-(4-hippuric acid)thiosemicarbazide and different carbonyl compounds as antimicrobial agents.
Eur J Med Chem
PUBLISHED: 02-15-2013
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New series of thiosemicarbazone derivatives incorporating a hippuric acid moiety have been synthesized through the reaction of N-(4-hippuric acid)thiosemicarbazide with various carbonyl compounds such as aldehydes, ketones and cyclic ketones. The synthesized compounds were tested against bacterial and fungal strains. Most of compounds, such as 2-(4-(2-(4-fluorobenzylidene)hydrazinecarbothioamido)benzamido)acetic acid showed significant antibacterial and antifungal activities. These compounds comprise a new class of promising broad-spectrum antibacterial and antifungal agents.
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Tissue distribution and efficacy of gold nanorods coupled with laser induced photoplasmonic therapy in ehrlich carcinoma solid tumor model.
PLoS ONE
PUBLISHED: 01-01-2013
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Gold nanorods (GNR) within tumor microregions are characterized by their ability to absorb near IR light and emit heat in what is called photoplasmonic effect. Yet, the efficacy of nanoparticles is limited due to intratumoral tissue distribution reasons. In addition, distribution of GNRs to normal tissue might result in non specific toxicity. In the current study, we are assessing the intratumoral and tissue distribution of PEGylated GNRs on the top of its antitumor characteristics when given intravenously or intratumoral to solid tumor bearing mice and coupled with laser photoplasmonic sessions. PEGylated GNRs with a longitudinal size of less than 100 nm were prepared with aspect ratio of 4.6 showing strong surface plasmon absorption at wavelength 800 nm. Pharmacokinetics of GNR after single I.V. administration (0.1 mg/kg) showed very short systemic circulating time (less than 3 h). On the other hand, tissue distribution of I.V. GNR (0.1 mg/kg) to normal animals showed preferential deposition in spleen tissue. Repeated administration of I.V. GNR resulted in preferential accumulation in both liver and spleen tissues. In addition, I.V. administration of GNR to Ehrlich carcinoma tumor bearing mice resulted in similar tissue distribution; tumor accumulation and anti-tumor effect compared to intratumoral administration. In conclusion, the concentration of GNR achieved within tumors microregions after I.V. administration was comparable to I.T. administration and sufficient to elicit tumoral growth arrest when coupled with laser-aided photoplasmonic treatment.
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Synthesis, in vitro anticancer screening and radiosensitizing evaluation of some new 4-[3-(substituted)thioureido]-N-(quinoxalin-2-yl)-benzenesulfonamide derivatives.
Acta Pharm
PUBLISHED: 12-29-2011
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Sulfonamides and quinoxaline derivatives possess many types of biological activities and have been recently reported to show substantial antitumor activity. This paper reports the synthesis of novel thioureido sulfaquinoxaline derivatives. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against a human liver cell line (HEPG2) and showed higher activity than the reference drug doxorubicin. 4-(3-(4-Ethylbenzoate) thioureido)-N-(quinoxalin-2-yl)benzenesulfonamide (9) (IC?? = 15.6 ?mol L?¹), N-(pyridin-2-yl)-4-(3-(4-(N-quinoxalin-2-yl-sulfamoyl)phenyl)thioureido)benzenesulfonamide (10) (IC?? = 26.8 ?mol L?¹) and N-(quinoxalin-2-yl)-4-(3-(4-(N-thiazol-2-ylsulfamoyl)phenyl)thioureido)benzenesulfonamide (11) (IC?? = 24.4 ?mol L?¹) were the most potent compared to doxorubicin (IC?? = 71.8 ?mol L?¹). The most potent compounds 9, 10 and 11 were evaluated as radiosensitizing agents by subjecting the compounds to ?-irradiation (8 kGy).
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Local inflammation influences oestrogen metabolism in prostatic tissue.
BJU Int.
PUBLISHED: 12-07-2011
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Whats known on the subject? and What does the study add? The role of oestrogen in prostatic inflammation has been extensively shown. The catechol oestrogens are known to be more potent oestrogenic moieties that not only aggravate the inflammatory response in situ, but are also believed to have oxidative stress and genotoxic effects. The present study highlights a significant role of inflammation in oestrogen metabolism and, particularly, in generating bad oestrogen metabolites. This finding may pave the way for new therapeutic methods for the treatment and/or prevention of prostate diseases.
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Postpartum thyroid dysfunction: a state of immunological dysregulation.
Clin. Lab.
PUBLISHED: 10-28-2011
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Postpartum thyroid dysfunction (PPTD) occurs in the first 12 months after delivery. This work was designed to compare thyroid peroxidase (TPO) and thyroglobulin (Tg) autoantibodies for determination of the diagnosis and, also, to detect role of lymphocytes in the pathogenesis of autoimmune thyroiditis.
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Polymeric human Fc-fusion proteins with modified effector functions.
Sci Rep
PUBLISHED: 08-23-2011
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The success of Fc-fusion bio-therapeutics has spurred the development of other Fc-fusion products for treating and/or vaccinating against a range of diseases. We describe a method to modulate their function by converting them into well-defined stable polymers. This strategy resulted in cylindrical hexameric structures revealed by tapping mode atomic force microscopy (AFM). Polymeric Fc-fusions were significantly less immunogenic than their dimeric or monomeric counterparts, a result partly owing to their reduced ability to interact with critical Fc-receptors. However, in the absence of the fusion partner, polymeric IgG1-Fc molecules were capable of binding selectively to Fc?Rs, with significantly increased affinity owing to their increased valency, suggesting that these reagents may prove of immediate utility in the development of well-defined replacements for intravenous immunoglobulin (IVIG) therapy. Overall, these findings establish an effective IgG Fc-fusion based polymeric platform with which the therapeutic and vaccination applications of Fc-fusion immune-complexes can now be explored.
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2,4-dinitrophenol (DNP): a weight loss agent with significant acute toxicity and risk of death.
J Med Toxicol
PUBLISHED: 07-09-2011
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2,4-Dinitrophenol (DNP) is reported to cause rapid loss of weight, but unfortunately is associated with an unacceptably high rate of significant adverse effects. DNP is sold mostly over the internet under a number of different names as a weight loss/slimming aid. It causes uncoupling of oxidative phosphorylation; the classic symptom complex associated with toxicity of phenol-based products such as DNP is a combination of hyperthermia, tachycardia, diaphoresis and tachypnoea, eventually leading to death. Fatalities related to exposure to DNP have been reported since the turn of the twentieth century. To date, there have been 62 published deaths in the medical literature attributed to DNP. In this review, we will describe the pattern and pathophysiology of DNP toxicity and summarise the previous fatalities associated with exposure to DNP.
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Chemometric methods for the simultaneous determination of some water-soluble vitamins.
J AOAC Int
PUBLISHED: 05-14-2011
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Two spectrophotometric methods, derivative and multivariate methods, were applied for the determination of binary, ternary, and quaternary mixtures of the water-soluble vitamins thiamine HCI (I), pyridoxine HCI (II), riboflavin (III), and cyanocobalamin (IV). The first method is divided into first derivative and first derivative of ratio spectra methods, and the second into classical least squares and principal components regression methods. Both methods are based on spectrophotometric measurements of the studied vitamins in 0.1 M HCl solution in the range of 200-500 nm for all components. The linear calibration curves were obtained from 2.5-90 microg/mL, and the correlation coefficients ranged from 0.9991 to 0.9999. These methods were applied for the analysis of the following mixtures: (I) and (II); (I), (II), and (III); (I), (II), and (IV); and (I), (II), (III), and (IV). The described methods were successfully applied for the determination of vitamin combinations in synthetic mixtures and dosage forms from different manufacturers. The recovery ranged from 96.1 +/- 1.2 to 101.2 +/- 1.0% for derivative methods and 97.0 +/- 0.5 to 101.9 +/- 1.3% for multivariate methods. The results of the developed methods were compared with those of reported methods, and gave good accuracy and precision.
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Synthesis and characterization of new types of halogenated and alkylated imidazolidineiminothiones and a comparative study of their antitumor, antibacterial, and antifungal activities.
Eur J Med Chem
PUBLISHED: 02-27-2011
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A series of twenty novel imidazolidineiminothiones (4-8) with various substituents at N-(1) and N-(3) were synthesized by various permutations of halogenated and alkylated N-arylcyanothioformanilides (1) with aromatic isocyanates (2). Preliminary screening of all compounds against Ehrlich ascites carcinoma cells (EAC) indicated that 5d, and 8a-c were the most active compounds as they displayed the highest percent inhibition of cell viability (80%, 70%, 80%, and 70%, respectively). Thus, they were further subjected to in vitro biological evaluation against other tumor cancer cell lines (HEPG2, HEP2, MCF7, HELA, and HCT116). The IC50 values ranged from 3.12 to 12.1 ?g/mL where compound 8b (N-(1): 2,4-dimethoxyphenyl; N-(3): 4-methoxyphenyl) was markedly active against all cell lines and consistently produced low IC50 values in all cases (ranging from 3.12 to 4.34 ?g/mL). This underscored the synergistic effect of the suitably positioned methoxy groups on the aromatic rings of N-(1) and N-(3) of the imidazolidineiminothiones. All compounds were also tested against microbial organisms (Escherichia coli, Sarcina lutea, Bacillus subtilis, and Staphylococcus aureus), and fungal strains (Candida albicans and Aspergillus flavus). Most tested compounds showed significant activities which could be optimized with the appropriate selection of matching aromatic substituents on N-(1) and N-(3).
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Clinical course of Crohns disease following treatment of lymphoma.
Inflamm. Bowel Dis.
PUBLISHED: 02-23-2011
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Crohns disease (CD) patients may be at increased risk for the development of Hodgkins lymphoma (HL) or non-Hodgkins lymphoma (NHL), either through exposure to immunosuppressive medications or due to their underlying chronic inflammatory illness. There are limited data regarding the natural history of CD following treatment of lymphoma. We present a series of CD patients who were treated for lymphoma and describe the natural history of their CD following lymphoma treatment.
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Ischemic kidney injury and mechanisms of tissue repair.
Wiley Interdiscip Rev Syst Biol Med
PUBLISHED: 01-04-2011
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Acute kidney injury (AKI) may result from ischemia or by the use of nephrotoxic agents. The incidence of AKI is variable, depends on comorbidities, and ranges from 5 to 35% in all hospitalized patients. The mechanisms of kidney injury exist within a large network of signaling pathways driven by interplay of inflammatory cytokines/chemokines, reactive oxygen species (ROS), and apoptotic factors. The effects and progression of injury overlap extensively with the remarkable ability of the kidney to repair itself both by intrinsic and extrinsic mechanisms that involve specific cell receptors/ligands as well as possible paracrine influences. The fact that kidney injury is usually part of a generalized comorbid condition makes it all the more challenging in terms of assessment of severity. In this review, we attempt to analyze the mechanisms of ischemic injury and repair in acute and chronic kidney disease from the perspectives of both preclinical and human studies.
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Pharmacological study of the effect of licorice alone and in combination with diclofenac sodium on hepatotoxicity-induced experimentally in rats.
J Complement Integr Med
PUBLISHED: 01-01-2011
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The protective effect of licorice and diclofenac sodium in doses of 50 mg/kg bwt. and 5 mg/kg bwt. respectively against liver toxicity induced by CCl4 (1ml/kg bwt.) in olive oil [1:1 (v/v)] every other day for 8 weeks and by hepatic ischemia/reperfusion in adult male albino rats was studied. Different antioxidant and liver function parameters were reported to find the protective effect of both licorice and diclofenac sodium against hepatotoxicity. Results showed that licorice protected against CCl4-induced hepatotoxicity as well as ischemia/reperfusion-induced liver injury. On the other hand, diclofenac sodium caused deleterious effects, especially in presence of CCl4, where a high mortality rate was observed.
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Effect of honey on 50% complement hemolytic activity in infants with protein energy malnutrition: a randomized controlled pilot study.
J Med Food
PUBLISHED: 12-27-2010
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Protein energy malnutrition (PEM) is associated with a significant impairment of cell-mediated immunity and complement system, which may be responsible for the high incidence of infections among these patients. This study was designed to examine the effect of honey, as a natural substance, on the 50% complement hemolytic activity (CH50) in patients with PEM. Thirty patients with PEM and 20 healthy infants serving as controls participated in this study. The patients were randomized to receive either honey (group 1) or placebo (group 2), in addition to conventional nutritional rehabilitation therapy. Measurements of weight, midarm circumference, skin fold thickness, serum albumin, and CH50 were done for all patients before and after 2 weeks of rehabilitation. Before nutritional rehabilitation, the CH50 was significantly lower in the PEM groups compared with the control. However, after rehabilitation, the CH50 increased significantly in both PEM groups, compared with the pre-interventional state and with the controls. Moreover, the rise of CH50 was significantly more in the honey group compared with the placebo. On the other hand, the improvement in the anthropometric measures and serum albumin did not differ significantly between the honey and placebo groups after rehabilitation. Thus honey supplementation in patients with PEM increased the level of CH50. Whether this would have an effect on the frequency and severity of infections in patients with PEM needs further studies.
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Impact of cytotoxin-associated gene A of Helicobacter pylori strains on microalbuminuria in type 2 diabetes.
Saudi J Kidney Dis Transpl
PUBLISHED: 07-01-2010
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Cytotoxin-associated gene A (CagA) positive strains of H. pylori have a significant correlation with gastritis and peptic ulcer, and may induce persistent systemic inflammatory response, increase vascular damage, and compromise glycemic control in diabetic patients. To evaluate correlation between infection by cagA positive strains of H. pylori and occurrence of microalbuminuria and glycemic control in type 2 diabetic patients, we prospectively studied 98 dyspeptic type 2 diabetic patients as a study group and 102 dyspeptic non-diabetic subjects as a control group. Gastric biopsy specimens obtained with endoscopy were cultured to isolate H. pylori. All the isolated H. pylori strains from cultures were used for detection of cagA gene by polymerase chain reaction. There was no significant difference between study and control groups regarding infection with cagA positive strains of H. pylori ( P= 0.145). Furthermore, there was no significant differences between both groups concerning the incidence of microalbuminuria ( P= 0.145). On the other hand, there was an extremely statistically significant difference in the incidence of microalbuminuria and glycemic control in the diabetic patients between those infected with cagA positive strains of H. pylori and cag A negative starins (P= 0.000). We conclude that infection with cagA positive strains of H. pylori are strongly associated with the increased incidence of microalbuminuria and poor glycemic control in type 2 diabetic patients.
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Potential protective effects of quercetin and curcumin on paracetamol-induced histological changes, oxidative stress, impaired liver and kidney functions and haematotoxicity in rat.
Food Chem. Toxicol.
PUBLISHED: 06-21-2010
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The present study was carried out to evaluate the potential protective role of quercetin and curcumin against paracetamol-induced oxidative injury, liver damage and impairment of kidney function, as well as haematotoxicity in rats. Also, N-acetylcysteine was used to evaluate the potency of quercetin and curcumin. Paracetamol caused an elevation in thiobarbituric acid-reactive substances (TBARS) paralleled with significant decline in glutathione peroxidase, glutathione S-transferase, superoxide dismutase and catalase activities (in plasma, brain, lung, heart, liver, kidney and testes) and glutathione content (in lung, liver and kidney). The apparent oxidative injury was associated with evident hepatic necrosis confirmed in histological examination, elevated plasma transmainases, alkaline phosphatase and lactate dehydrogenase. Paracetamol reduced plasma total protein, albumin and globulin, while increased bilirubin, urea and creatinine, and induced haematotoxicity. The presence of quercetin or curcumin with paracetamol successfully mitigated the rise in TBARS and restored the activities of antioxidant enzymes compared to the group treated with both paracetamol and N-acetylcysteine. They also protected liver histology, normalized liver and kidney functions, which was more pronounced with curcumin. Therefore, it can be concluded that concomitant administration of quercetin or curcumin with paracetamol may be useful in reversing the toxicity of the drug compared to N-acetylcysteine.
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Synthesis of novel pyrrole and pyrrolo[2,3-d]pyrimidine derivatives bearing sulfonamide moiety for evaluation as anticancer and radiosensitizing agents.
Bioorg. Med. Chem. Lett.
PUBLISHED: 05-12-2010
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Pyrroles and pyrrolo[2,3-d]pyrimidines were reported to act as potent anticancer agents, in this work, a series of novel 2-substituted-3-cyano-4-phenyl-pyrrole 5, 6, 11-18, and 5-phenyl-pyrrolo[2,3-d]pyrimidine derivatives 7-10, 19-24 bearing either sulfathiazole or sulfapyridine were synthesized. The structures of these compounds were confirmed by elemental analysis, IR, (1)H NMR and mass spectral data. All the newly synthesized compounds were evaluated for their in vitro cytotoxicity against liver and breast cancer cell line (HEPG2 and MCF7). Most of the screened compounds showed interesting cytotoxic activities compared with the used reference drug (doxorubicin). The radiosensitizing ability of some of the synthesized compounds was studied and the results showed an increase in the cell killing effect of ?-radiation after combination with the tested compounds.
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Application of oxybutynin selective sensors for monitoring the dissolution profile and assay of pharmaceutical dosage forms.
Anal Sci
PUBLISHED: 04-23-2010
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Two ion-selective sensors of the plastic membrane type were prepared for the determination of oxybutynin hydrochloride (OxCl). They depend on the incorporation of the ion-associates with phosphotungestic acid or phosphomolybdic acid in a PVC matrix. A comparative study is made between their performance characteristics in batch and FIA conditions. The sensors have nearly the same usable concentration, temperature and pH range. They have a wide range of selectivity and can be applied for the determination of the relevant drug with nearly the same precision and accuracy in vitro. Dissolution testing was applied using the sensors; this offers a simple, rapid, cheap way out of sophisticated and high cost instruments used in the pharmacopeial method using HPLC. The investigated drug was determined in its pure and pharmaceutical preparations. The results were accurate and precise, as indicated by the recovery values and coefficients of variation.
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Efficacy of aqueous garlic extract on growth, aflatoxin B1 production, and cyto-morphological aberrations of Aspergillus flavus, causing human ophthalmic infection: topical treatment of A. flavus keratitis.
Braz. J. Microbiol.
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By using agar well diffusion assay, antifungal activity of aqueous extract prepared from Egyptian garlic (Allium sativum L.) was evaluated in vitro against two strains of Aspergillus flavus (OC1 and OC10) causing human ocular infection. The recorded minimum inhibitory concentration (MIC) for growth inhibition of both strains was 3.60 mg/ml. Aqueous garlic extract (AGE) was used in successive in vivo tests as an attempt to cure rabbits fungal keratitis caused by A. flavus OC1. Findings showed that diluted preparation of AGE was effective topical antifungal agent and succeeded to cure severe A. flavus keratitis in a time course less than 10 days without any observable side effects. Microscopic examination showed that AGE induced deleterious cyto-morphological aberrations in A. flavus target cells. AGE applied to Czapeks broth via contact method was more effective on growth, spores and aflatoxin B1 production than AGE applied to the same broth at the same concentration via fumigation method.
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Infrared and electron spin resonance spectral studies of some copper purine and pyrimidine complexes.
Spectrochim Acta A Mol Biomol Spectrosc
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Copper guanine and barbital complexes were prepared and characterized by elemental analyses and spectral measurements. The data typified the formation of stoichiometries 1:1 (M:L) with possible Cu-Cu interaction "association". The complexes are with different geometries: square planar, square pyramidal and tetrahedral. The mode of bonding was identified by IR spectra. EPR spectra of the powdered complexes were recorded at X band at the room temperature. Different ESR parameters were calculated and discussed: g(//), g(?), A(//), [g], G, F, K, ?(2). Molecular modeling techniques and quantum chemical methods have been performed for copper complexes to correlate the chemical structures of the complexes with their physical molecular properties. Bond lengths, bond orders, bond angles, dihedral angles, close contact, dipole moment (?), sum of the total negative charge (STNC), electronegativity (?), chemical potential (Pi), global hardness (?), softness (?), the highest occupied molecular orbital energy (E(HOMO)), the lowest unoccupied molecular orbital energy (E(LUMO)) and the energy gap (?E) were calculated using PM3 semi-empirical and Molecular Mechanics (MM+) methods. The study displays a good correlation between the theoretical and experimental data which confirms the reliability of the quantum chemical methods.
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Cows Milk Allergy Is a Major Contributor in Recurrent Perianal Dermatitis of Infants.
ISRN Pediatr
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Background. Recurrent perianal inflammation has great etiologic diversity. A possible cause is cows milk allergy (CMA). The aim was to assess the magnitude of this cause. Subjects and Methods. This follow up clinical study was carried out on 63 infants with perianal dermatitis of more than 3 weeks with history of recurrence. Definitive diagnosis was made for each infant through medical history taking, clinical examination and investigations including stool analysis and culture, stool pH and reducing substances, perianal swab for different cultures and staining for Candida albicans. Complete blood count and quantitative determination of cows milk-specific serum IgE concentration were done for all patients. CMA was confirmed through an open withdrawal-rechallenge procedure. Serum immunoglobulins and CD markers as well as gastrointestinal endoscopies were done for some patients. Results. Causes of perianal dermatitis included CMA (47.6%), bacterial dermatitis (17.46%), moniliasis (15.87%), enterobiasis (9.52%) and lactose intolerance (9.5%). Predictors of CMA included presence of bloody and/or mucoid stool, other atopic manifestations, anal fissures, or recurrent vomiting. Conclusion. We can conclude that cows milk allergy is a common cause of recurrent perianal dermatitis. Mucoid or bloody stool, anal fissures or ulcers, vomiting and atopic manifestations can predict this etiology.
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Pancreatic and biliary secretion are both altered in cystic fibrosis pigs.
Am. J. Physiol. Gastrointest. Liver Physiol.
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The pancreas, liver, and gallbladder are commonly involved in cystic fibrosis (CF), and acidic, dehydrated, and protein-rich secretions are characteristic findings. Pancreatic function studies in humans have been done by sampling the jejunal fluid. However, it has been difficult to separately study the function of pancreatic and biliary systems in humans with CF, because jejunal fluid contains a mixture of bile and pancreatic fluids. In contrast, pancreatic and biliary ducts open separately into the porcine intestine; therefore, biliary and pancreatic fluid can be individually analyzed in CF pigs. We studied newborn wild-type (WT) and CF pigs and found that CFTR was localized to the pancreatic ducts. We collected bile and pancreatic fluid and analyzed pancreatic enzymes with activity assays and immunoblot. Pancreatic enzyme expression was significantly decreased in CF compared with WT pigs. The volume and pH of pancreatic fluid were significantly lower and protein concentration was >5-fold higher in CF pigs. Secretin stimulation increased pancreatic fluid volume and pH in WT, but not CF, pigs. Baseline bile volume did not differ between WT and CF pigs, but volume did not increase in response to secretin in CF pigs. Bile pH was lower and protein concentration was twofold higher in CF pigs. These results indicate that pancreatic and biliary secretions are altered in CF pigs. Abnormal pancreatic and biliary secretion in CF may have important implications in disease pathogenesis.
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Recurrent blood eosinophilia in ulcerative colitis is associated with severe disease and primary sclerosing cholangitis.
Dig. Dis. Sci.
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Eosinophils are implicated in the pathogenesis of inflammatory bowel disease (IBD). A subset of IBD patients develops blood eosinophilia, and the clinical profile of these patients is undefined. We sought to characterize IBD patients with and without eosinophilia.
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Pancreatic damage in fetal and newborn cystic fibrosis pigs involves the activation of inflammatory and remodeling pathways.
Am. J. Pathol.
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Pancreatic disease has onset in utero in humans with cystic fibrosis (CF), and progresses over time to complete destruction of the organ. The exact mechanisms leading to pancreatic damage in CF are incompletely understood. Inflammatory cells are present in the pancreas of newborn pigs with CF (CF pigs) and humans, which suggests that inflammation may have a role in the destructive process. We wondered whether tissue inflammation and genes associated with inflammatory pathways were increased in the pancreas of fetal CF pigs [83 to 90 days gestation (normal pig gestation is ~114 days)] and newborn pigs. Compared with fetal pigs without CF (non-CF pigs), in fetal CF pigs, the pancreas exhibited patchy inflammation and acinar atrophy, with progression in distribution and severity in neonatal CF pigs. Large-scale transcript profiling revealed that the pancreas in fetal and newborn CF pigs exhibited significantly increased expression of proinflammatory, complement cascade, and profibrotic genes when compared with fetal and newborn non-CF pigs. Acinar cells exhibited increased apoptosis in the pancreas of fetal and newborn CF pigs. ?-Smooth muscle actin and transforming growth factor ?1 were increased in both fetal and newborn CF pig pancreas, suggesting activation of profibrotic pathways. Cell proliferation and mucous cell metaplasia were detected in newborn, but not fetal, CF pigs, indicating that they were not an initiator of pathogenesis but a response. Proinflammatory, complement cascade, proapoptotic, and profibrotic pathways are activated in CF pig pancreas, and likely contribute to the destructive process.
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Simplified and versatile method for isolation of high-quality RNA from pancreas.
BioTechniques
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Isolation of high-quality RNA from pancreas is challenging because the organ contains large quantities of RNases and undergoes autolysis upon harvest. Here we present a simplified perfusion method of the pancreas using an RNase inhibitor. The technique consistently yields high-quality RNA from stored pancreas samples suitable for molecular biology applications, including quantitative RT-PCR. Yields are comparable to RNA isolated from pancreas immediately, but superior to RNA isolated from stored samples that were snap-frozen or immersed in an RNase inhibitor solution. In addition, when compared to the previously reported in situ ductal perfusion technique, our method does not cause histological artifacts.
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Fluorescence characteristics and inclusion of ICT fluorescent probe in organized assemblies.
J Fluoresc
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The inclusion behavior of an intramolecular charge transfer (ICT) fluorescent probe namely; 2-[3-(4-dimethylamino-phenyl)-allylidene]-tetralone (DMAPT) in organized assemblies of aqueous micellar, ?- and ?-cyclodextrins (CDs) and bovine serum albumin (BSA) pockets have been studied using steady-state absorption and fluorescence spectroscopy. The fluorescence characteristics (energy and intensity) of DMAPT are highly sensitive to the properties of the medium. The ICT maximum is strongly blue-shifted with a great enhancement of the fluorescence intensity upon addition of different surfactants, confirming the solubilization of DMAPT in the hydrophobic micellar assembly. In addition, the fluorescence of DMAPT is more sensitive to the nature and concentration of the added CDs. In ?- or ?-CD solutions, the fluorescence intensity increases strongly (by 6 and 23 orders of magnitude, respectively). Upon encapsulation in the CD cavity, the molecular flexibility decreases due to the geometrical restrictions of the CD nanocavity which decreases the non radiative transition via the free rotation around the single and/or double bonds of the butadiene bridge. This was supported by finding that the fluorescence quantum yield of DMAPT increases with increasing the viscosity of the medium. The binding constants of DMAPT with micelles, ?- and ?-CD solutions have been calculated and were found to be highly dependent on the nature of the used surfactants or CDs. The thermodynamic parameters have been also determined and the difference in magnitude between the formed ?- and ?-CD-DMAPT inclusion complexes is discussed on the basis of the cavity size. Finally, the binding constant of DMAPT with bovine serum albumin was calculated, indicating the relative stability of the DMAPT-BSA complex. The energy transfer distance between BSA as a donor and DMAPT as an acceptor was obtained following the fluorescence quenching of BSA by DMAPT, via resonance mechanism as a quencher.
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Adiponectin: an adipocyte-derived hormone, and its gene encoding in children with chronic kidney disease.
BMC Res Notes
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The prevalence of cardiovascular disease (CVD) and inflammation is high in patients with chronic kidney disease (CKD). Adiponectin (ADPN) is an adipocytokine that may have significant anti-inflammatory and anti-atherosclerotic effects. Low adiponectin levels have previously been found in patients with high risk for CVD.
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Chemical speciation and equilibria of some nucleic acid compounds and their iron(III) complexes.
Spectrochim Acta A Mol Biomol Spectrosc
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The pH effect on electronic absorption spectra of some biologically active nucleic acid constituents have been studied at room temperature and the mechanism of ionization was explained. These compounds are of two categories (pyrimidines: [barbital; 5,5-diethyl-barbituric acid], [SBA; 4,6-dihydroxy-2-mercapto-pyrimidin], [NBA; 5-nitro-2,4,6(1H,3H,5H)-pyrimidine trione] and [TU; 2,3-dihydro-2-thioxo-pyrimidin-4(1H)-one]) and (purines: [adenine; 6-amino purine], its [Schiff bases derived from adenine-acetylacetone; (Z)-4-(7H-purin-6-ylimino)pentan-2-one) and adenine-salicylaldehyde; 2-((7H-purin-6-ylimino) methyl) phenol] and its [Azo derived from adenine-resorcinol; 4-((7H-purin-6-yl)-diazenyl) benzene-1,3-diol]. The phenomena of tautomerization assigned different tautomers. Different spectrophotometric methods are applied to evaluate the pKs values that explained with their molecular structures. The interaction of Fe(3+) with some selected pyrimidines (barbital, NBA and SBA) was explained using familiar six spectrophotometric methods. The data typified the existence of different absorbing species with the different stoichiometries 1:1, 1:2, 1:3 and 2:3. The stability constant of the complexes was computed. More approach was deduced to assign the existence of different species applying the distribution diagrams.
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Immunohistochemical Expression of ER?, ER?, and TFF1 in Type I and II Ovarian Tumors.
Appl. Immunohistochem. Mol. Morphol.
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Surface epithelial tumors of the ovary are no longer considered as a single disease but are divided into types I and II on the basis of their molecular features, cell of origin, and their behavior. A possible direct action of gonadal steroids on ovarian carcinogenesis has been suggested. The current information about the possible role of TFF1 in ovarian tumors,, together with its relationship to the estrogen receptor (ER) status, is insufficient. The aim of this study was to investigate ER?, ER?, and TFF1 expression in type I and II ovarian tumors and their correlation with clinicopathologic parameters of each type. The present study was carried out on 97 ovarian tumors [20 benign, 15 borderline, and 62 malignant (36 type I and 26 type II tumors)]. ER? expression was significantly in favor of type II tumors (P=0.04), whereas high TFF1 expression was significantly in favor of type I tumors (P=0.02). ER? and ER? showed a significant positive correlation in benign cases (P=0.004) and in type I tumors (P=0.006), but not in type II tumors. In type I tumors, the expression of ER? was correlated with serous carcinoma (P=0.002) and bilaterality (P=0.05), whereas TFF1 was correlated with mucinous carcinoma (P=0.02), unilaterality (P=0.04), early FIGO staging (P=0.01), and a low mitotic count (P=0.03). A high ER?:ER? H score ratio was associated with advanced FIGO staging in both type I (P=0.05) and type II tumors (P=0.009). The difference in the expression of ER? and TFF1 between type I and II tumors may be indicative of the difference in their origin and molecular pathway. The ER?:ER? ratio is more important in determining the net result of ER effects than the evaluation of each receptor separately, and the high ratio may promote progression to advanced stage in type I and II ovarian tumors. High TFF1 expression in ovarian mucinous carcinoma may indicate that their mucinous differentiation is toward an intestinal type rather than an endocervical type. TFF1 expression in ovarian tumors seems to occur independent of the status of the ER.
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