Publications by authors named "Mehmet Kara"

27 Publications

  • Page 1 of 1

EBV miRNAs are potent effectors of tumor cell transcriptome remodeling in promoting immune escape.

PLoS Pathog 2021 May 6;17(5):e1009217. Epub 2021 May 6.

Department of Pathology, Tulane University School of Medicine, Tulane Cancer Center, New Orleans, Louisiana, United States of America.

The Epstein Barr virus (EBV) contributes to the tumor phenotype through a limited set of primarily non-coding viral RNAs, including 31 mature miRNAs. Here we investigated the impact of EBV miRNAs on remodeling the tumor cell transcriptome. Strikingly, EBV miRNAs displayed exceptionally abundant expression in primary EBV-associated Burkitt's Lymphomas (BLs) and Gastric Carcinomas (GCs). To investigate viral miRNA targeting, we used the high-resolution approach, CLASH in GC and BL cell models. Affinity constant calculations of targeting efficacies for CLASH hits showed that viral miRNAs bind their targets more effectively than their host counterparts, as did Kaposi's sarcoma-associated herpesvirus (KSHV) and murine gammaherpesvirus 68 (MHV68) miRNAs. Using public BL and GC RNA-seq datasets, we found that high EBV miRNA targeting efficacies translates to enhanced reduction of target expression. Pathway analysis of high efficacy EBV miRNA targets showed enrichment for innate and adaptive immune responses. Inhibition of the immune response by EBV miRNAs was functionally validated in vivo through the finding of inverse correlations between EBV miRNAs and immune cell infiltration and T-cell diversity in BL and GC datasets. Together, this study demonstrates that EBV miRNAs are potent effectors of the tumor transcriptome that play a role in suppressing host immune response.
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http://dx.doi.org/10.1371/journal.ppat.1009217DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130916PMC
May 2021

Bond Strength of Metal and Ceramic Brackets on Resin Nanoceramic Material With Different Surface Treatments.

Turk J Orthod 2020 Jun 1;33(2):115-122. Epub 2020 Jun 1.

Department of Orthodontics, Dicle University School of Dentistry, Diyarbakır, Turkey.

Objective: This study aimed to evaluate the effects of different surface conditoning methods on surface texture and shear bond strength (SBS) of brackets bonded to resin nanoceramic material.

Methods: Ceramic specimens were divided into two groups as metal brackets and ceramic brackets. In each group, the following five subgroups were conditoned with orthophosphoric acid (OPA), hydrofluoric acid (HFA), silica coating with Cojet, Nd: Yag laser, and Femtosecond (Fs) laser. Extra samples were used for scanning electron microscopy and 3D profilometer evaluation.

Results: All surface conditioning methods caused optimum or higher SBS. Metal brackets had higher SBS than porcelain brackets, but this difference reached statistical significance only in Fs laser group. OPA caused surface modification comparable to HFA because of polymer content of resin nanoceramic. Although Fs laser and Cojet conditioning caused optimum or higher SBS, surface damage of these methods to the resin nanoceramic specimens clearly seen on 3D profilometer.

Conclusion: HFA and Nd: Yag laser are effective surface conditioning methods for resin nanoceramics. OPA combined with silane application caused optimum SBS and can be used as an alternative to HFA. Surface texture changes should be considered to determine surface damage while deciding the optimum surface conditioning method for ceramics other than SBS.
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http://dx.doi.org/10.5152/TurkJOrthod.2020.19103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316482PMC
June 2020

Multi-criteria decision-making using GIS-AHP for air pollution problem in Igdir Province/Turkey.

Environ Sci Pollut Res Int 2020 Oct 18;27(29):36215-36230. Epub 2020 Jun 18.

Department of Electric Electronic Engineering, Engineering Faculty, Igdir University, 76000, Igdir, Turkey.

Today, environmental problems are increasing and threatening nature and human health. Air pollution is at the top of this threat. Air, the main source of life, is indispensable for humans and living things. Therefore, air pollution causes mass results. Many air pollution studies and many solution techniques have been proposed in the literature to deal with the air pollution problem. In this study, it is called analytical hierarchy process (AHP) and geographic information systems (GIS), which is one of the multi-criteria decision making methods used in the investigation of air pollution in Iğdır city center and its four districts: Tuzluca, Iğdır Central, Karakoyunlu, and Aralik. In this study, spatial analysis of the pollutant parameters using the GIS-AHP technique was performed with the help of the data obtained from Iğdır Weather Monitoring Stations. By determining the pollutant parameters, pollution distribution maps were created, and station-based statistics were evaluated with dynamic mapping. For the first time, 15 parameters of weather and topographic features were used. Based on this result, it is obvious that Iğdır center is the worst place in the air pollution problem for GIS-AHP method. It varies for 15 parameters using GIS-AHP, compared with the review of locations on a daily basis. The aim of this study is primarily to investigate possible places of air pollution. Also, by comparing the results of two methods, GIS and AHP, more accurate results are given.
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http://dx.doi.org/10.1007/s11356-020-09710-3DOI Listing
October 2020

Canal Flare Index in the Canine Femur Is Influenced by the Measurement Method.

Vet Comp Orthop Traumatol 2020 May 30;33(3):198-204. Epub 2020 Mar 30.

Department of Anatomy, Faculty of Veterinary Medicine, Adnan Menderes University, Aydin, Turkey.

Objectives:  We evaluated whether differences exist among the canal flare index (CFI) values obtained by different calculation methods in the veterinary literature.

Study Design:  The endosteal widths were measured from radiographic images of canine cadaveric femora. Three different formulae were used to calculate the CFI. The CFI was the ratio of endosteal width at the medial aspect of the lesser trochanter (LT) to the midshaft (M), while the CFI was the ratio of LT to the isthmus (I). The CFI was the ratio of endosteal width at the proximal aspect of the lesser trochanter (PLT) and the I. The widths at each level and the CFI calculation methods were compared. Using Rashmir-Raven's method, the femora were typed as stovepipe, normal and champagne fluted. The limits of agreement were also evaluated.

Results:  The endosteal width at the proximal aspect of the lesser trochanter was 12% wider than at the medial aspect and 8% wider at the midshaft than at the isthmus. The CFI was less than CFI and CFI by 9 and 20%, respectively. By Rashmir-Raven's classification, the CFI method provided 18% stovepipe, 79% normal and 3% champagne fluted femora. The CFI method showed the stovepipe, the normal and the champagne fluted as 6, 82 and 12%, respectively. The CFI method classified the femora either normal (55%) or champagne fluted (45%). The comparison of CFI with the other methods using Bland-Altman analysis showed lower mean difference for the CFI than the CFI.

Conclusion:  The level of width measurements at proximal femora might have an impact on the CFI values, likewise, preoperative planning procedures and the selection of a stem type in total hip arthroplasty.
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http://dx.doi.org/10.1055/s-0040-1701501DOI Listing
May 2020

Identification of murine gammaherpesvirus 68 miRNA-mRNA hybrids reveals miRNA target conservation among gammaherpesviruses including host translation and protein modification machinery.

PLoS Pathog 2019 08 8;15(8):e1007843. Epub 2019 Aug 8.

Dept. of Molecular Genetics and Microbiology, UF Health Cancer Center, University of Florida, Gainesville, Florida, United States of America.

Gammaherpesviruses, including the human pathogens Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), establish lifelong latent infection in B cells and are associated with a variety of tumors. In addition to protein coding genes, these viruses encode numerous microRNAs (miRNAs) within their genomes. While putative host targets of EBV and KSHV miRNAs have been previously identified, the specific functions of these miRNAs during in vivo infection are largely unknown. Murine gammaherpesvirus 68 (MHV68) is a natural pathogen of rodents that is genetically related to both EBV and KSHV, and thus serves as an excellent model for the study of EBV and KSHV genetic elements such as miRNAs in the context of infection and disease. However, the specific targets of MHV68 miRNAs remain completely unknown. Using a technique known as qCLASH (quick crosslinking, ligation, and sequencing of hybrids), we have now identified thousands of Ago-associated, direct miRNA-mRNA interactions during lytic infection, latent infection and reactivation from latency. Validating this approach, detailed molecular analyses of specific interactions demonstrated repression of numerous host mRNA targets of MHV68 miRNAs, including Arid1a, Ctsl, Ifitm3 and Phc3. Notably, of the 1,505 MHV68 miRNA-host mRNA targets identified in B cells, 86% were shared with either EBV or KSHV, and 64% were shared among all three viruses, demonstrating significant conservation of gammaherpesvirus miRNA targeting. Pathway analysis of MHV68 miRNA targets further revealed enrichment of cellular pathways involved in protein synthesis and protein modification, including eIF2 Signaling, mTOR signaling and protein ubiquitination, pathways also enriched for targets of EBV and KSHV miRNAs. These findings provide substantial new information about specific targets of MHV68 miRNAs and shed important light on likely conserved functions of gammaherpesvirus miRNAs.
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http://dx.doi.org/10.1371/journal.ppat.1007843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687095PMC
August 2019

Genome-wide Transcript Structure Resolution Reveals Abundant Alternate Isoform Usage from Murine Gammaherpesvirus 68.

Cell Rep 2019 06;27(13):3988-4002.e5

Department of Molecular Genetics & Microbiology, UF Health Cancer Center, University of Florida, Gainesville, FL, USA. Electronic address:

The gammaherpesviruses, including Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and murine gammaherpesvirus 68 (MHV68, MuHV-4, γHV68), are etiologic agents of a wide range of lymphomas and non-hematological malignancies. These viruses possess large and highly dense dsDNA genomes that feature >80 bidirectionally positioned open reading frames (ORFs). The abundance of overlapping transcripts and extensive splicing throughout these genomes have until now prohibited high throughput-based resolution of transcript structures. Here, we integrate the capabilities of long-read sequencing with the accuracy of short-read platforms to globally resolve MHV68 transcript structures using the transcript resolution through integration of multi-platform data (TRIMD) pipeline. This approach reveals highly complex features, including: (1) pervasive overlapping transcript structures; (2) transcripts containing intra-gene or trans-gene splices that yield chimeric ORFs; (3) antisense and intergenic transcripts containing ORFs; and (4) noncoding transcripts. This work sheds light on the underappreciated complexity of gammaherpesvirus transcription and provides an extensively revised annotation of the MHV68 transcriptome.
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http://dx.doi.org/10.1016/j.celrep.2019.05.086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071827PMC
June 2019

Cutaneous Anthrax Outbreak in the Trakya Region of Turkey

Balkan Med J 2019 05 31;36(3):196-197. Epub 2019 Jan 31.

Department of Infectious Diseases, Trakya University School of Medicine, Edirne, Turkey

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http://dx.doi.org/10.4274/balkanmedj.galenos.2019.2018.12.19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6528531PMC
May 2019

Effects of Leontice leontopetalum and Bongardia chrysogonum on oxidative stress and neuroprotection in PTZ kindling epilepsy in rats.

Cell Mol Biol (Noisy-le-grand) 2018 Dec 31;64(15):71-77. Epub 2018 Dec 31.

Department of Biology, Faculty of Science, Van Yuzuncu Yil University, Van, Turkey.

We investigated the effects of Leontice leontopetalum and Bongardia chrysogonum on apoptosis, gamma-aminobutyric acid (GABAA) receptor positive cell number, cyclin-B1 and bcl-2 levels and oxidative stress in pentylenetetrazol (PTZ) kindling in rats. Kindling was produced by subconvulsant doses of PTZ treatments in rats. Wistar albino rats were divided into 4 groups; Control, PTZ treated (PTZ), PTZ+L. leontopetalum extract treated (PTZ+LLE) and PTZ+B. chrysogonum extract treated (PTZ+BCE) groups. Extracts were given a dose (200 mg/kg) 2h before each PTZ injection. PTZ treatment significantly decreased the glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) activities and bcl-2 levels and increased the total oxidant status (TOS), malondialdehyde (MDA), cyclin B1, oxidative stress index (OSI) and number of neurons that expressed GABAA receptors when compared to the control. LLE and BCE possessed antioxidant activity in the brain and ameliorated PTZ induced oxidative stress, decreased cyclin-B1, increased bcl-2 levels, and kept the GABAA receptor number similar to that of the control despite the PTZ application.
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December 2018

Gammaherpesvirus Readthrough Transcription Generates a Long Non-Coding RNA That Is Regulated by Antisense miRNAs and Correlates with Enhanced Lytic Replication In Vivo.

Noncoding RNA 2019 Jan 10;5(1). Epub 2019 Jan 10.

Department of Molecular Genetics & Microbiology, UF Health Cancer Center, University of Florida, Gainesville, Florida, 32610, USA.

Gammaherpesviruses, including the human pathogens Epstein⁻Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are oncogenic viruses that establish lifelong infections in hosts and are associated with the development of lymphoproliferative diseases and lymphomas. Recent studies have shown that the majority of the mammalian genome is transcribed and gives rise to numerous long non-coding RNAs (lncRNAs). Likewise, the large double-stranded DNA virus genomes of herpesviruses undergo pervasive transcription, including the expression of many as yet uncharacterized lncRNAs. Murine gammaperherpesvirus 68 (MHV68, MuHV-4, HV68) is a natural pathogen of rodents, and is genetically and pathogenically related to EBV and KSHV, providing a highly tractable model for studies of gammaherpesvirus biology and pathogenesis. Through the integrated use of parallel data sets from multiple sequencing platforms, we previously resolved transcripts throughout the MHV68 genome, including at least 144 novel transcript isoforms. Here, we sought to molecularly validate novel transcripts identified within the locus, which harbors genes that code for the chemokine binding protein M3, the latency B cell signaling protein M2, and 10 microRNAs (miRNAs). Using strand-specific northern blots, we validated the presence of a 3.91 kb polyadenylated transcript that initiates at the M3 transcription start site and reads through the M3 open reading frame (ORF), the M3 poly(a) signal sequence, and the M2 ORF. This unexpected transcript was solely localized to the nucleus, strongly suggesting that it is not translated and instead may function as a lncRNA. Use of an MHV68 mutant lacking two -antisense pre-miRNA stem loops resulted in highly increased expression of and increased virus replication in the lungs of infected mice, demonstrating a key role for these RNAs in regulation of lytic infection. Together these findings suggest the possibility of a tripartite regulatory relationship between the lncRNA , antisense miRNAs, and the latency gene .
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http://dx.doi.org/10.3390/ncrna5010006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468771PMC
January 2019

Evaluation of ghrelin, nesfatin-1 and irisin levels of serum and brain after acute or chronic pentylenetetrazole administrations in rats using sodium valproate.

Neurol Res 2018 Nov 15;40(11):923-929. Epub 2018 Aug 15.

a Department of Physiology, Faculty of Medicine , Van Yuzuncu Yil University , Van , Turkey.

Objectives: In this study, we aim to reveal the alterations (due to seizure) in the serum and brain levels of nesfatin-1, ghrelin and irisin after acute or chronic pentylenetetrazole administrations in rats using sodium valproate.

Methods: 35 Wistar albino rats were randomly divided into five groups: Control, Acute Pentylenetetrazole group (APTZ), Acute Pentylenetetrazole+ Valproate group (AVPA), PTZ kindling group (PTZk) and PTZ kindling+ Valproate group (KVPA). Serum and brain levels of ghrelin, nesfatin-1 and FNDC5/irisin were determined with ELISA.

Results: Serum levels of ghrelin were significantly decreased in APTZ and PTZk groups compared to the control (p < 0.01). There was a statistically significant decrease in brain levels of ghrelin in all groups compared to the control group (p < 0.01). There was a statistically significant increase in serum nesfatin-1 levels in the APTZ and PTZk groups compared to the control (p < 0.05). Serum levels of nesfatin-1 were similar to the control group in both the acute and the chronic treatment groups. There was a statistically significant increase in brain nesfatin-1 levels of the KVPA group compared to the control (p < 0.05). Serum and brain levels of FNDC5/irisin were found significantly increased in APTZ, AVPA and PTZk groups compared to the control (p < 0.01).

Conclusions: Statistically significant alterations were detected in the serum and brain levels of these three peptides in both the PTZ-induced chronic epilepsy model and acute seizure model. The results of this study may suggest that the increase in FNDC5/irisin and nesfatin-1 levels, and the decrease in ghrelin levels may contribute to seizure pathophysiology. However, further studies are needed in order to confirm our hypothesis.
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http://dx.doi.org/10.1080/01616412.2018.1503992DOI Listing
November 2018

Effects of Cichorium intybus on serum oxidative stress, liver and kidney volume, and cyclin B1 and Bcl-2 levels in the brains of rats with ethanol induced damage.

Cell Mol Biol (Noisy-le-grand) 2018 May 30;64(7):30-35. Epub 2018 May 30.

Department of Histology and Embryology, Faculty of Medicine, Van Yuzuncu Yil University, Van, Turkey.

We investigated the effects of an aqueous root extract of Cichorium intybus on Bcl-2 and cyclin B1 levels in the brain, kidney and liver volumes and changes of serum total antioxidant status (TAS) and total oxidant status (TOS) levels in ethanol induced damage in rats. The rats were divided into five groups: non-treated controls (C), maltodextrin in tap water treated (MD), 6.4% ethanol in tap water treated (ET), Cichorium intybus + maltodextrin in tap water treated (CI+MD), and Cichorium intybus + 6.4% ethanol in tap water treated (CI+ET). Rats in the CI+MD and CI+ET groups were treated with 200 mg/kg water extract of Cichorium intybus. Chronic ethanol aMDinistration significantly increased cyclin B1 and decreased Bcl-2 levels in the brain and significantly decreased TAS values, increased TOS values of serum and significantly decreased kidney volume in the ET group. There was no significant difference in the liver volume or liver cell count. Our data revealed that ethanol aMDinistration induces an overexpression of cyclin B1 and decreases levels of Bcl-2 in rat brains and induced oxidative stress in the blood. C. intybus treatment possessed a partial amelioration effect on cyclin B1 levels and TAS values.
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May 2018

Proximal and distal alignment of normal canine femurs: A morphometric analysis.

Ann Anat 2018 May 19;217:125-128. Epub 2018 Mar 19.

Istanbul University, Faculty of Veterinary Medicine, Department of Anatomy, Istanbul, Turkey.

Many researchers are interested in femoral conformation because most orthopaedic problems of the long bones occur in the femur and its joints. The neck-shaft (NSA) and the anteversion (AVA) angles are good predictors for understanding the orientation of the proximal end of the femur. The varus (aLDFA) and procurvatum (CDFA) angles have also been used to understand the orientation of the distal end of the femur. The purposes of this study were to investigate the relationship between the proximal and distal angles of the femur and to compare the distal femoral angles in male and female dogs in order to investigate the sexual dimorphism. The measurements of normal CDFAs, which have not been previously reported, may also provide a database of canine distal femoral morphology. A total of 75 cleaned healthy femora from different breeds or mixed breed of dogs were used. The three-dimensional images were reconstructed from computed tomographic images. The AVA, NSA, aLDFA and CDFA were measured on the 3D images. The correlation coefficients were calculated among the measured angles. The distal femoral angles were also compared between male and female femora. The 95% confidence intervals of the AVA and the NSA were calculated to be 24.22°-29.50° and 144.97°-147.50°, respectively. The 95% confidence intervals of the aLDFA and the CDFA for all studied dogs were 92.62°-94.08° and 89.09°-91.94°, respectively. The NSA showed no correlation with either the aLDFA or CDFA. There was a weak inverse correlation between the AVA and CDFA and a weak positive correlation between the AVA and aLDFA. The differences in the aLDFA and CDFA measurements between male and female dog were not significant. In conclusion, femoral version, regardless of the plane, might have little influence on distal femoral morphology in normal dogs. Besides this, there is no evidence of a sexual dimorphism in the varus and procurvatum angles of the dog distal femur. The data from this study may be used in both orthopaedic studies and for clinical applications related to the distal femur of dogs.
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http://dx.doi.org/10.1016/j.aanat.2018.02.006DOI Listing
May 2018

High Doses of Boron Have No Protective Effect Against Nephrolithiasis or Oxidative Stress in a Rat Model.

Biol Trace Elem Res 2018 Nov 8;186(1):218-225. Epub 2018 Mar 8.

Department of Pediatrics, University of Health Sciences, Kayseri Training and Research Hospital, Kayseri, Turkey.

Boron plays roles in the metabolism of calcium, vitamin D, steroid hormones, healthy bone development, and maintenance of cell membranes. The biological effects of boron are dose-dependent but follow a U-shaped pattern, rendering it important to define the active range. The studies of Bahadoran et al. on rats and Naghii et al. on humans showed that low doses of boron (3 and 10 mg/day) prevented kidney stone formation. The aim of this study was to determine whether high doses of boron have an anti-urolithiatic or antioxidant effect on nephrolithiasis in an experimental rat model. The study was conducted on 50 adult male Wistar rats randomized to five groups. Nephrolithiasis was induced with water containing 0.75% ethylene glycol (EG) and 2% ammonium chloride (AC). This treatment was given to animals in all groups for 10 days, except the positive and negative controls. Simultaneously, groups 2, 3, and 4 were given boric acid via gavage at doses of 25, 50, and 100 mg/kg/day (equivalent to 4/8/16 mg boron respectively) as the source of boron. Animals in the negative and positive control groups were given 6 μL/g distilled water without boric acid. At day 10, intra-cardiac blood samples were drawn from all animals. The right and left kidneys were removed for biochemical and histopathological examinations, respectively. The groups were compared with respect to serum urea, creatinine, calcium, phosphorous, total antioxidant status (TAS), total oxidant status (TOS), serum paraoxonase (PON1) activity, tissue calcium and oxalate levels, and stone burden as determined by histopathological examination. Serum urea and creatinine levels were significantly higher (p < 0.001 and p < 0.05, respectively), while serum calcium and phosphorous levels were significantly lower (p < 0.001 and p < 0.001, respectively), in animals given EG/AC compared to negative controls. No significant differences were detected in serum calcium, phosphorous, urea, or creatinine levels between animals treated with boron and positive controls (p > 0.05). Serum PON1 activity was significantly lower in animals given EG/AC than in negative controls (p < 0.001), while no significant difference in serum PON1 level was detected between rats treated with boron and positive controls. No significant differences were detected in vitamin D, TAS, TOS, tissue calcium, or tissue oxalate levels among groups. No stone formation was detected on histopathological examination in negative controls. No significant differences were found in stone formation between rats treated with boron and positive controls. Based on this study, high doses of boron had no protective effect against nephrolithiasis and oxidative stress.
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http://dx.doi.org/10.1007/s12011-018-1294-1DOI Listing
November 2018

Viral FGARAT ORF75A promotes early events in lytic infection and gammaherpesvirus pathogenesis in mice.

PLoS Pathog 2018 02 1;14(2):e1006843. Epub 2018 Feb 1.

Department of Molecular Genetics and Microbiology, Stony Brook University, Stony Brook, New York, United States of America.

Gammaherpesviruses encode proteins with homology to the cellular purine metabolic enzyme formyl-glycinamide-phosphoribosyl-amidotransferase (FGARAT), but the role of these viral FGARATs (vFGARATs) in the pathogenesis of a natural host has not been investigated. We report a novel role for the ORF75A vFGARAT of murine gammaherpesvirus 68 (MHV68) in infectious virion production and colonization of mice. MHV68 mutants with premature stop codons in orf75A exhibited a log reduction in acute replication in the lungs after intranasal infection, which preceded a defect in colonization of multiple host reservoirs including the mediastinal lymph nodes, peripheral blood mononuclear cells, and the spleen. Intraperitoneal infection rescued splenic latency, but not reactivation. The 75A.stop virus also exhibited defective replication in primary fibroblast and macrophage cells. Viruses produced in the absence of ORF75A were characterized by an increase in the ratio of particles to PFU. In the next round of infection this led to the alteration of early events in lytic replication including the deposition of the ORF75C tegument protein, the accelerated kinetics of viral gene expression, and induction of TNFα release and cell death. Infecting cells to deliver equivalent genomes revealed that ORF75A was required for initiating early events in infection. In contrast with the numerous phenotypes observed in the absence of ORF75A, ORF75B was dispensable for replication and pathogenesis. These studies reveal that murine rhadinovirus vFGARAT family members ORF75A and ORF75C have evolved to perform divergent functions that promote replication and colonization of the host.
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http://dx.doi.org/10.1371/journal.ppat.1006843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811070PMC
February 2018

The mixture of liquid foam soap, ethanol and citric acid as a new fixative-preservative solution in veterinary anatomy.

Ann Anat 2017 Jan 13;209:11-17. Epub 2016 Oct 13.

Department of Histology and Embryology, Faculty of Veterinary Medicine, University of Adnan Menderes, Aydin, Turkey.

The present study investigates the efficiency of liquid foam soap, ethanol, citric acid and benzalkonium chloride as a fixative-preservative solution (a soap-and ethanol-based fixing solution, or SEFS). In this study, ethanol serves as the fixative and preservative, liquid foam soap as the modifying agent, citric acid as the antioxidant and benzalkonium chloride as the disinfectant. The goat cadavers perfused with SEFS (n=8) were evaluated over a period of one year with respect to hardness, colour and odour using objective methods. Colour and hardness were compared between one fresh cadaver and the SEFS-embalmed cadavers. Histological and microbiological examinations were also performed in tissue samples. Additionally, the cadavers were subjectively evaluated after dissection and palpation. The SEFS provided the effectiveness expected over a 1-year embalming period for the animal cadavers. No bacteria or fungi were isolated except for some non-pathogenic Bacillus species. Visible mould was not present on either cadavers or in the surrounding environment. The cadavers maintained an appearance close to their original anatomical appearance, with muscles having good hardness and elasticity for dissection.
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http://dx.doi.org/10.1016/j.aanat.2016.09.002DOI Listing
January 2017

A Gammaherpesvirus Noncoding RNA Is Essential for Hematogenous Dissemination and Establishment of Peripheral Latency.

mSphere 2016 Apr 2;1(2). Epub 2016 Mar 2.

Department of Molecular Genetics and Microbiology and UF Health Cancer Center, College of Medicine, University of Florida, Gainesville, Florida, USA.

Recent intense investigations have uncovered important functions for a diverse array of novel noncoding RNA (ncRNA) species, including microRNAs (miRNAs) and long noncoding RNAs. Not surprisingly, viruses from multiple families have evolved to encode their own regulatory RNAs; however, the specific functions of these ncRNAs are largely unknown. The human gammaherpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are highly ubiquitous pathogens that are associated with the development of a wide range of malignancies, including Burkitt's lymphoma, Hodgkin's lymphoma, nasopharyngeal carcinoma, and Kaposi's sarcoma. Like EBV and KSHV, murine gammaherpesvirus 68 (MHV68) establishes lifelong latency in B cells and is associated with lymphoproliferative disease and lymphoma. Similar to the EBV-encoded small RNA (EBER)-1 and -2, MHV68 encodes eight 200- to 250-nucleotide polymerase III-transcribed ncRNAs called TMERs (tRNA-miRNA-encoded RNAs), which are highly expressed in latently infected cells and lymphoproliferative disease. To define the contribution of TMERs to MHV68 biology, we generated a panel of individual TMER mutant viruses. Through comprehensive analyses, we identified TMER4 as a key mediator of virus dissemination. The TMER4 mutant virus replicated normally in lungs and spread with normal kinetics and distribution to lung-draining lymph nodes, but it was significantly attenuated for infection of circulating blood cells and for latency establishment at peripheral sites. Notably, TMER4 stem-loops but not miRNAs were essential for wild-type TMER4 activity. Thus, these findings revealed a crucial miRNA-independent function of the TMER4 ncRNA in MHV68 hematogenous dissemination and latency establishment.

Importance: Noncoding RNAs (ncRNAs) represent an intriguing and diverse class of molecules that are now recognized for their participation in a wide array of cellular processes. Viruses from multiple families have evolved to encode their own such regulatory RNAs; however, the specific functions of these ncRNAs are largely unknown. Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) are ubiquitous human pathogens that are associated with the development of numerous malignancies. Like EBV and KSHV, murine gammaherpesvirus 68 (MHV68) establishes lifelong latency in B cells and is associated with lymphomagenesis. The work described here reveals that the MHV68 ncRNA TMER4 acts at a critical bottleneck in local lymph nodes to facilitate hematogenous dissemination of the virus and establishment of latency at peripheral sites.
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http://dx.doi.org/10.1128/mSphere.00105-15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838037PMC
April 2016

6β-Hydroxytestosterone, a Cytochrome P450 1B1-Testosterone-Metabolite, Mediates Angiotensin II-Induced Renal Dysfunction in Male Mice.

Hypertension 2016 May 29;67(5):916-26. Epub 2016 Feb 29.

From the Department of Pharmacology (A.K.P., S.T., M.K., K.U.M.) and Department of Medicine and Microbiology, Immunology and Biochemistry (D.D.B.), College of Medicine, University of Tennessee Health Science Center, Memphis; Veterans Affairs Medical Center, Memphis, TN (D.D.B.); Tulane Hypertension and Renal Center of Excellence, Department of Physiology, School of Medicine, Tulane University, New Orleans, LA (A.K., D.S.A.M., L.G.N.); and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD (F.J.G.).

6β-Hydroxytestosterone, a cytochrome P450 1B1-derived metabolite of testosterone, contributes to the development of angiotensin II-induced hypertension and associated cardiovascular pathophysiology. In view of the critical role of angiotensin II in the maintenance of renal homeostasis, development of hypertension, and end-organ damage, this study was conducted to determine the contribution of 6β-hydroxytestosterone to angiotensin II actions on water consumption and renal function in male Cyp1b1(+/+) and Cyp1b1(-/-) mice. Castration of Cyp1b1(+/+) mice or Cyp1b1(-/-) gene disruption minimized the angiotensin II-induced increase in water consumption, urine output, proteinuria, and sodium excretion and decreases in urine osmolality. 6β-Hydroxytestosterone did not alter angiotensin II-induced increases in water intake, urine output, proteinuria, and sodium excretion or decreases in osmolality in Cyp1b1(+/+) mice, but restored these effects of angiotensin II in Cyp1b1(-/-) or castrated Cyp1b1(+/+) mice. Cyp1b1 gene disruption or castration prevented angiotensin II-induced renal fibrosis, oxidative stress, inflammation, urinary excretion of angiotensinogen, expression of angiotensin II type 1 receptor, and angiotensin-converting enzyme. 6β-Hydroxytestosterone did not alter angiotensin II-induced renal fibrosis, inflammation, oxidative stress, urinary excretion of angiotensinogen, expression of angiotensin II type 1 receptor, or angiotensin-converting enzyme in Cyp1b1(+/+)mice. However, in Cyp1b1(-/-) or castrated Cyp1b1(+/+) mice, it restored these effects of angiotensin II. These data indicate that 6β-hydroxytestosterone contributes to increased thirst, impairment of renal function, and end-organ injury associated with angiotensin II-induced hypertension in male mice and that cytochrome P450 1B1 could serve as a novel target for treating renal disease and hypertension in male mice.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.115.06936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833582PMC
May 2016

6β-hydroxytestosterone, a cytochrome P450 1B1 metabolite of testosterone, contributes to angiotensin II-induced hypertension and its pathogenesis in male mice.

Hypertension 2015 Jun 13;65(6):1279-87. Epub 2015 Apr 13.

From the Department of Pharmacology, College of Medicine (A.K.P., M.K., N.S.K., A.M.E., K.U.M.) and Department of Pharmaceutical Sciences, College of Pharmacy (Z.L., W.L.), University of Tennessee, Health Science Center, Memphis; and Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, Bethesda, MD (F.J.G.).

Previously, we showed that Cyp1b1 gene disruption minimizes angiotensin II-induced hypertension and associated pathophysiological changes in male mice. This study was conducted to test the hypothesis that cytochrome P450 1B1-generated metabolites of testosterone, 6β-hydroxytestosterone and 16α-hydroxytestosterone, contribute to angiotensin II-induced hypertension and its pathogenesis. Angiotensin II infusion for 2 weeks increased cardiac cytochrome P450 1B1 activity and plasma levels of 6β-hydroxytestosterone, but not 16α-hydroxytestosterone, in Cyp1b1(+/+) mice without altering Cyp1b1 gene expression; these effects of angiotensin II were not observed in Cyp1b1(-/-) mice. Angiotensin II-induced increase in systolic blood pressure and associated cardiac hypertrophy, and fibrosis, measured by intracardiac accumulation of α-smooth muscle actin, collagen, and transforming growth factor-β, and increased nicotinamide adenine dinucleotide phosphate oxidase activity and production of reactive oxygen species; these changes were minimized in Cyp1b1(-/-) or castrated Cyp1b1(+/+) mice, and restored by treatment with 6β-hydroxytestoterone. In Cyp1b1(+/+) mice, 6β-hydroxytestosterone did not alter the angiotensin II-induced increase in systolic blood pressure; the basal systolic blood pressure was also not affected by this agent in either genotype. Angiotensin II or castration did not alter cardiac, angiotensin II type 1 receptor, angiotensin-converting enzyme, Mas receptor, or androgen receptor mRNA levels in Cyp1b1(+/+) or in Cyp1b1(-/-) mice. These data suggest that the testosterone metabolite, 6β-hydroxytestosterone, contributes to angiotensin II-induced hypertension and associated cardiac pathogenesis in male mice, most probably by acting as a permissive factor. Moreover, cytochrome P450 1B1 could serve as a novel target for developing agents for treating renin-angiotensin and testosterone-dependent hypertension and associated pathogenesis in males.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.115.05396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4433413PMC
June 2015

Supplemental carvacrol can reduce the severity of inflammation by influencing the production of mediators of inflammation.

Inflammation 2015 ;38(3):1020-7

Department of Medical Biochemistry, Faculty of Medicine, Eskisehir Osmangazi University, Eskisehir, Turkey,

Carvacrol (CVC) is a monoterpenic phenol, which is present in the essential oil of various plants. It has been widely used both as antibacterial feed additive and food preservative. Therefore, our objective was to evaluate the prophylactic effects of carvacrol on inflammatory mediators of sepsis. Serum tumor necrosis factor alpha and interleukin 6 levels as proinflammatory markers were evaluated using an enzyme-linked immunosorbent assay technique. Malondialdehyde (MDA) was determined in the sample by using thiobarbituric acid test. Nitric oxide (NO) levels and arginase activity and also all measurements were evaluated after 24 h from lipopolysaccharide (LPS) injections done (1 mg/kg i.p.). All carvacrol doses (20, 40, and 80 mg/kg) were given by intra gastric gavage during six days before LPS injection (7th day). Proinflammatory cytokines, MDA, NO levels, and arginase activity were decreased by carvacrol according to the carvacrol doses. These results indicate that carvacrol may have a potent anti-inflammatory and antioxidant effects in a dose-dependent manner. Subchronic use of CVC can be assisted to pre-treat of sepsis as a prophylactic.
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http://dx.doi.org/10.1007/s10753-014-0066-0DOI Listing
February 2016

Alveolar bone protective and hypoglycemic effects of systemic propolis treatment in experimental periodontitis and diabetes mellitus.

J Med Food 2015 Feb 29;18(2):195-201. Epub 2014 Sep 29.

1 Department of Periodontology, Faculty of Dentistry, Sifa University , Izmir, Turkey .

The aim of this study was to evaluate the efficacy of the anti-inflammatory effects of propolis on the systemic and local effects on experimental periodontitis and diabetes. Fifty-six Wistar rats were divided into seven groups: (1) negative-control (NC), (2) periodontitis (P), (3) diabetes (D), (4) diabetes+periodontitis (DP), (5) periodontitis+propolis (P-Pro), (6) diabetes+propolis (D-Pro), and (7) diabetes+periodontitis+propolis (DP-Pro). Periodontitis was induced by ligature placement and diabetes was induced by streptozotocin injection. Propolis (Pro) was administrated by oral gavage (100 mg/kg/day). On day 21, plasma was obtained for analysis and alveolar bone level was evaluated using histomorphometric analysis. Compared to NC the final blood glucose levels for D-Pro was not significantly different (P=.052), however, D, DP, and DP-Pro were significantly different. There were no statistically significant differences in blood glucose concentrations between P and P-Pro, between D and D-Pro, and between DP and DP-Pro. All groups showed significantly more alveolar bone loss compared with NC. A significant difference in bone loss was found between P and P-Pro, and DP and DP-Pro, however there was no difference between D and D-Pro. Plasma interleukin 1beta (IL-1β), tumor necrosis factor-alpha (TNF-α), and matrix metalloproteinase-8 (MMP-8) levels were not significantly different among groups. In conclusion, propolis reduced fasting blood glucose levels in diabetes. In addition, propolis might be beneficial as an adjunct treatment of diabetes associated periodontitis and periodontitis without diabetes.
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http://dx.doi.org/10.1089/jmf.2013.3137DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4312799PMC
February 2015

Virus-encoded microRNAs facilitate gammaherpesvirus latency and pathogenesis in vivo.

mBio 2014 May 27;5(3):e00981-14. Epub 2014 May 27.

Department of Molecular Genetics & Microbiology and UF Shands Cancer Center, College of Medicine, University of Florida, Gainesville, Florida, USA

Unlabelled: Gammaherpesviruses, including Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV, or HHV-8), and murine gammaherpesvirus 68 (MHV68, γHV68, or MuHV-4), are B cell-tropic pathogens that each encode at least 12 microRNAs (miRNAs). It is predicted that these regulatory RNAs facilitate infection by suppressing host target genes involved in a wide range of key cellular pathways. However, the precise contribution that gammaherpesvirus miRNAs make to viral life cycle and pathogenesis in vivo is unknown. MHV68 infection of mice provides a highly useful system to dissect the function of specific viral elements in the context of both asymptomatic infection and disease. Here, we report (i) analysis of in vitro and in vivo MHV68 miRNA expression, (ii) generation of an MHV68 miRNA mutant with reduced expression of all 14 pre-miRNA stem-loops, and (iii) comprehensive phenotypic characterization of the miRNA mutant virus in vivo. The profile of MHV68 miRNAs detected in infected cell lines varied with cell type and did not fully recapitulate the profile from cells latently infected in vivo. The miRNA mutant virus, MHV68.Zt6, underwent normal lytic replication in vitro and in vivo, demonstrating that the MHV68 miRNAs are dispensable for acute replication. During chronic infection, MHV68.Zt6 was attenuated for latency establishment, including a specific defect in memory B cells. Finally, MHV68.Zt6 displayed a striking attenuation in the development of lethal pneumonia in mice deficient in IFN-γ. These data indicate that the MHV68 miRNAs may facilitate virus-driven maturation of infected B cells and implicate the miRNAs as a critical determinant of gammaherpesvirus-associated disease.

Importance: Gammaherpesviruses such as EBV and KSHV are widespread pathogens that establish lifelong infections and are associated with the development of numerous types of diseases, including cancer. Gammaherpesviruses encode many small noncoding RNAs called microRNAs (miRNAs). It is predicted that gammaherpesvirus miRNAs facilitate infection and disease by suppressing host target transcripts involved in a wide range of key cellular pathways; however, the precise contribution that these regulatory RNAs make to in vivo virus infection and pathogenesis is unknown. Here, we generated a mutated form of murine gammaherpesvirus (MHV68) to dissect the function of gammaherpesvirus miRNAs in vivo. We demonstrate that the MHV68 miRNAs were dispensable for short-term virus replication but were important for establishment of lifelong infection in the key virus reservoir of memory B cells. Moreover, the MHV68 miRNAs were essential for the development of virus-associated pneumonia, implicating them as a critical component of gammaherpesvirus-associated disease.
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http://dx.doi.org/10.1128/mBio.00981-14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045068PMC
May 2014

Serum nerve growth factor (NGF) levels in children with attention deficit/hyperactivity disorder (ADHD).

Neurosci Lett 2014 Feb 19;560:107-11. Epub 2013 Dec 19.

Ankara Pediatric & Pediatric Hematology Oncology Training and Research Hospital, Department of Medical Biochemistry, Ankara, Turkey.

Attention deficit/hyperactivity disorder (ADHD) is the most commonly diagnosed neurobehavioral disorder of childhood. The etiopathogeny of ADHD has not been totally defined. Recent reports have suggested a pathophysiological role of neurotrophins in ADHD. In this study, we evaluated serum levels of nerve growth factor (NGF) in patients with ADHD. The sample population consisted of 44 child or adolescent patients diagnosed with ADHD according to DSM-IV criteria; 36 healthy subjects were included in the study as controls. Venous blood samples were collected, and NGF levels were measured. The mean serum NGF levels of the ADHD patients were significantly higher than those of the controls. Age and gender of the patients were not correlated with serum NGF levels. There were no significant differences in NGF levels among the combined and predominantly inattentive subtypes of ADHD. Our study suggests that there are higher levels of serum NGF in drug naive ADHD patients, and that increased levels of NGF might have an important role in the pathophysiology of ADHD.
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http://dx.doi.org/10.1016/j.neulet.2013.12.026DOI Listing
February 2014

Relationship between adipocytokines and cardiovascular risk factors in patients with type 2 diabetes mellitus.

Exp Ther Med 2012 Jul 23;4(1):113-120. Epub 2012 Apr 23.

Departments of Medical Biochemistry.

The aim of this study was to explore the relationship between serum profiles of adiponectin, leptin, resistin and visfatin and traditional and non-traditional cardiovascular risk factors in patients with type 2 diabetes mellitus (T2DM). A total of 85 patients with T2DM and 30 non-diabetic controls were enrolled in the study. Levels of adipocytokines (adiponectin, leptin, resistin and visfatin), lipids (total cholesterol, triglycerides), lipoproteins [HDL-cholesterol, LDL-cholesterol, lipoprotein (a)], apolipoproteins (Apo-A1 and Apo-B), non-traditional cardiovascular risk markers [asymmetric dimethylarginine (ADMA), homocysteine] and the inflammatory marker hs-CRP were measured, and anthropometric variables were determined. Serum adiponectin levels were decreased and leptin, resistin and visfatin levels were increased in T2DM patients compared to controls. They were associated with obesity (BMI), insulin resistance (HOMA-IR) and various markers of glucose/lipid profile, inflammation and endothelial dysfunction markers. These results suggest that decreased serum adiponectin and increased leptin, resistin and visfatin levels in T2DM may be novel biochemical risk factors for cardiovascular complications.
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http://dx.doi.org/10.3892/etm.2012.557DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460256PMC
July 2012

Effects of lipoprotein-associated phospholipase A2 on arginase/nitric oxide pathway in hemodialysis patients.

Ren Fail 2012 14;34(6):738-43. Epub 2012 May 14.

Department of Medical Biochemistry, School of Medicine, Unıiversity of Eskişehir Osmangazi, Eskişehir, Turkey.

Lipoprotein-associated phospholipase A2 (Lp-PLA2) and arginase are recently described inflammatory biomarkers associated with cardiovascular disease. In this study, we aimed to investigate the possible effects of serum Lp-PLA2 mass levels on arginase/nitric oxide (NO) pathway as a cardiovascular risk marker in hemodialysis (HD) patients. Forty-three HD patients and 15 healthy subjects were included in this study. Lipid profile, high sensitivity C-reactive protein (hs-CRP), albumin, creatinine, body mass index (BMI), Lp-PLA2 and total nitrite levels, and arginase activity were determined in serum samples from patients and control subjects. Lp-PLA2 levels were found to be positively correlated with arginase, triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and age and negatively correlated with high-density lipoprotein-cholesterol and total nitrite levels, while there was no correlation with BMI and hs-CRP, albumin, and creatinine levels in HD patients. We conclude that elevated Lp-PLA2 mass levels may contribute to impaired arginase/NO pathway in HD patients and that increased the arginase activity and Lp-PLA2 mass levels with decreased total nitrite levels seem to be useful biochemical markers in terms of reflecting endothelial dysfunction and associated cardiovascular risks in HD patients.
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http://dx.doi.org/10.3109/0886022X.2012.681535DOI Listing
October 2012

The anatomical study on the rat pancreas and its ducts with emphasis on the surgical approach.

Ann Anat 2005 Apr;187(2):105-12

Department of Anatomy, Veterinary Faculty, Adnan Menderes University, 09016 Isikli-AYDIN, Turkey.

It was intended to present information about the anatomy of the pancreas and especially to emphasize the variation of pancreatic ducts in the rat, which may guide researchers in experimental studies. In 27 adult rats, latex dye was introduced into the biliopancreatic duct, portal vein and arteries. The pancreas with the neighboring structures was studied with the aid of the dissection microscope and measurements were by means of micrometric ocular. The pancreas was divided into three parts i.e. the biliary, duodenal and gastrosplenic portions. The biliopancreatic and pancreatic ducts as well as biliary and duodenal portions of the pancreas could be seen ventrally with a minor procedure such as pulling the duodenum caudally, and additionally the entire pancreas and its ducts could also be reached dorsally since the stomach was turned cranially with the duodenum. The biliopancreatic duct diameter and length of the ducts were 1.01+/-0.03 and 28.86+/-0.59 mm, respectively. The anterior pancreatic duct originated from the biliopancreatic duct on different sides, 17.96+/-0.75mm away from the duodenal papilla. The anterior pancreatic duct drained the gastrosplenic portion of the rat pancreas and this duct, via the duodenal duct, partially collected secretion of the duodenal portion at a ratio of 74.07%. The posterior pancreatic duct opened to the biliopancreatic duct and its distance from papilla duodeni was changed from 0 to 8 mm. When the biliopancreatic duct is ligated at the level of the duodenal opening, the posterior pancreatic duct or a small duct from duodenal portion should be taken into consideration because these ducts opened to biliopancreatic duct at the level of papilla duodeni at a ratio of 37.04%. In conclusion, the duct system of pancreas had a great variation and therefore the success rate of the surgery could be increased when surgeons have more knowledge on variations of the duct system in this region.
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http://dx.doi.org/10.1016/j.aanat.2004.10.004DOI Listing
April 2005

Computed tomographic assessment of the trachea in the German shepherd dog.

Ann Anat 2004 Aug;186(4):317-21

Adnan Menderes University, Veterinary Faculty, Department of Anatomy, PK: 17 09016 Isikli, Aydin/Turkey.

Computed tomographic (CT) examination of the trachea was performed in 10 German shepherd dogs to determine the normal value of some tracheal measurements under general anesthesia and in sternal recumbence position. Measurements obtained from nine segments were evaluated in four groups as the cranial cervical, caudal cervical, thoracic inlet and the thoracal tracheas. The inner transverse (T) and vertical (V) diameters were measured with the aid of electronic calipers from the software of the CT scanner. The cross-sectional lumen area (CSA) was calculated by using vertical and transverse diameters. The ratio of the transverse and vertical diameters (T/V) was also calculated. There was not any significant difference between thoracic inlet and thoracic tracheas, however, the mentioned regions were found to be significantly different from both cranial and caudal cervical regions in all measurements except the ratio of T/V. The ratio of T/V between 0.92 and 1.06 gradually changed and there was not any statistical difference between subsequent regions while differences were found among further regions. The largest CSA, seen in cranial cervical trachea was as 364.62 mm2 and decreased gradually to 309.29, 245.69 and 226.50 mm2 in caudal cervical, thoracic inlet and thoracic tracheas, respectively. From the point of view of technique, CT examination of the dog trachea was very easy and it was possible to take sensitive and repeated measurements. It, however, may be accepted as expensive and that it is disadvantageous to require general anesthesia. The data presented in this study represent tracheal values in the healthy German shepherd dog under the conditions of the study.
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http://dx.doi.org/10.1016/S0940-9602(04)80048-7DOI Listing
August 2004