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1.
Drug Chem Toxicol ; : 1-11, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38726977

RESUMEN

Tenofovir alafenamide (TAF) is a new drug from the nucleotide reverse transcriptase inhibitor group approved for the treatment of chronic Hepatitis B in 2016. With this study, we aimed to test whether possible cellular toxicity can be reduced by controlled drug release as a result of loading with chitosan nanoparticles (CHS). We investigated the genotoxic and mitotoxic effects of 45 µM TAF-loaded CHS and TAF-only on HepG2 cells by micronucleus (MN), comet assay, determination of mtDNA quantification, mitochondrial membrane potential (ΔΨm), and ROS levels. Additionally, we compared the samples by RNAseq analyses to reveal the transcriptional responses to each regimen. In terms of genotoxic tests, although MN and comet were found higher in all experimental treatment conditions, the encapsulation of CHS reduced the genotoxicity of TAF. MtDNA level was found to be lower in the TAF treatment, whereas it was higher in CHS and CHS-TAF treatments. The TAF-loaded CHS and TAF treatments had an impaired ΔΨm value. Cellular ROS levels were higher in all treatment conditions. According to the analyses of gene expression patterns; CHS-only changed the expression of relatively few genes (187 genes), while TAF changed the expression of the 1974 genes and TAF-loaded CHS changed the expression of 734 genes. Considering the gene expression numbers, CHS encapsulation of TAF significantly reduced the number of genes that were differentially expressed by TAF-only. Overall, we observed that TAF has genotoxic and mitotoxic effects on HepG2 cells, and upon encapsulation with CHS, its genotoxic and mitotoxic effects were decreased.

2.
Cytokine ; 179: 156615, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38640560

RESUMEN

Familial Mediterranean Fever (FMF) is caused by mutations in pyrin, a protein produced in innate immune cells that regulates the development of interleukin (IL)-1ß by interacting with caspase-1 and other components of inflammasomes. Although overexpression of proinflammatory cytokines have been observed in FMF patients, no studies have been conducted on the role of Src family kinases (SFKs). The purpose of this study was to examine the impact of SFKs on the modulation of IL-1ß, IL-6, IL-8, TNF-α, and NLRP3 inflammasome in patients with FMF. The study included 20 FMF patients and 20 controls. Peripheral blood mononuclear cells (PBMCs) were isolated by density gradient centrifugation. Protein expression levels of SFKs members were measured by western blot. The effect of lipopolysaccharide-induced (LPS) activation and PP2- induced inhibition of SFKs on NLRP3 and IL-1ß, IL 6, IL-8, TNF-α were examined by western blot and flow cytometry respectively. Patients with FMF have considerably greater levels of Lck expression. In addition, patients had a substantially greater basal level of NLRP3 than the control group (*p = 0.016). Most importantly, the levels of IL-1 ß were elevated with LPS stimulation and reduced with PP2 inhibition in FMF patients. These results suggest that SFKs are effective in regulation of IL-1 ß in FMF patients.


Asunto(s)
Citocinas , Fiebre Mediterránea Familiar , Proteína con Dominio Pirina 3 de la Familia NLR , Familia-src Quinasas , Humanos , Fiebre Mediterránea Familiar/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Masculino , Femenino , Citocinas/metabolismo , Adulto , Familia-src Quinasas/metabolismo , Lipopolisacáridos/farmacología , Inflamasomas/metabolismo , Leucocitos Mononucleares/metabolismo , Adulto Joven , Proteínas Portadoras/metabolismo , Interleucina-1beta/metabolismo , Mediadores de Inflamación/metabolismo
3.
J Cell Mol Med ; 28(8): e18246, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38520223

RESUMEN

Here, it was aimed to investigate the effects of intracerebroventricular (ICV) Brain Derived Neurotrophic Factor (BDNF) infusion for 7 days following cerebral ischemia (CI) on autophagy in neurons in the penumbra. Focal CI was created by the occlusion of the right middle cerebral artery. A total of 60 rats were used and divided into 4 groups as Control, Sham CI, CI and CI + BDNF. During the 7-day reperfusion period, aCSF (vehicle) was infused to Sham CI and CI groups, and BDNF infusion was administered to the CI + BDNF group via an osmotic minipump. By the end of the 7th day of reperfusion, Beclin-1, LC3, p62 and cleaved caspase-3 protein levels in the penumbra area were evaluated using Western blot and immunofluorescence. BDNF treatment for 7 days reduced the infarct area after CI, induced the autophagic proteins Beclin-1, LC3 and p62 and suppressed the apoptotic protein cleaved caspase-3. Furthermore, rotarod and adhesive removal test times of BDNF treatment started to improve from the 4th day, and the neurological deficit score from the 5th day. ICV BDNF treatment following CI reduced the infarct area by inducing autophagic proteins Beclin-1, LC3 and p62 and inhibiting the apoptotic caspase-3 protein while its beneficial effects were apparent in neurological tests from the 4th day.


Asunto(s)
Isquemia Encefálica , Daño por Reperfusión , Ratas , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ratas Sprague-Dawley , Caspasa 3 , Beclina-1 , Isquemia Encefálica/metabolismo , Apoptosis , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Autofagia , Infarto , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/tratamiento farmacológico
4.
J Biol Inorg Chem ; 28(8): 725-736, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37934281

RESUMEN

In this study, a series of N-functionalized benzimidazole silver(I) complexes were prepared and characterized by FT-IR, 1H, 13C{1H} NMR spectroscopy, and elemental analysis. Synthesized N-benzylbenzimidazole silver(I) complexes were evaluated for their antimicrobial activities against bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and the fungal strains Candida albicans and Candida glabrata. The results indicated that N-alkylbenzimidazole silver(I) complexes exhibited good antimicrobial activity compared to N-alkylbenzimidazole derivatives. Especially, complex 2e presented perfect antimicrobial activity than the other complexes. The characterized molecules were optimized by DFT-based calculation methods and the optimized molecules were analyzed in detail by molecular docking methods against bacterial DNA-gyrase and CYP51. The amino acid residues detected for both target molecules are consistent with expectations, and the calculated binding affinities and inhibition constants are promising for further studies. A series of N-alkylbenzimidazole silver(I) complexes were synthesized and fully characterized by means of 1H NMR, 13C NMR, and FT-IR spectroscopies. Synthesized N-alkylbenzimidazole silver(I) complexes were investigated for their antimicrobial activities against bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and the fungal strains Candida albicans and Candida glabrata. All complexes showed better activity according to Ampicilin against Pseudomonas aeruginosa. The molecules which were firstly optimized by DFT-based calculation methods were also analyzed by molecular docking methods against DNA gyrase of E. Coli and CYP51. 338 × 190 mm (96 × 96 DPI).


Asunto(s)
Antiinfecciosos , Plata , Plata/farmacología , Plata/química , Simulación del Acoplamiento Molecular , Espectroscopía Infrarroja por Transformada de Fourier , Escherichia coli , Candida albicans , Bacterias , Antiinfecciosos/farmacología , Antiinfecciosos/química , Bencimidazoles/farmacología , Bencimidazoles/química , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología
5.
Turk Arch Pediatr ; 58(5): 531-538, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37670552

RESUMEN

OBJECTIVE: Despite marked improvements in the accessibility of childhood vaccines, knowledge gaps remain about the vaccination of children in special risk groups (SRG). This study aimed to analyze the clinical data of children vaccinated in SRG in a single-center unit to contribute to the clinical evidence for the specific planning of immunization of children in SRG. The second- ary aim is to present institutional consensus on the vaccination of children in SRG. MATERIALS AND METHODS: This retrospective study was conducted at a single-center pediatric vaccination clinic. Patient charts between 2018 and 2021 were retrospectively reviewed, and clinical and laboratory data were extracted. Serial joint meetings with multiple healthcare pro- fessionals were performed to develop an institutional protocol for vaccination. RESULTS: There were 479 children vaccinated between 2018 and 2021 for reasons such as post- chemotherapy, after hematopoietic stem cell transplantation, before/after solid organ trans- plantation, allergies, and chronic diseases. Of these, 298 (62.2%) children vaccinated in the unit due to a history of food or vaccine allergies were excluded. One hundred eighty-one children were vaccinated at a median age of 11 [7-15] years. Most children were vaccinated after treat- ment for malignancies. Solid tumors were the most frequent malignancy (67%), followed by acute lymphoblastic leukemia (29.0%) and acute myeloid leukemia (4.0%). Institutional vacci- nation protocols for cancer survivors, hematopoietic stem cells, and solid organ recipient chil- dren were developed and presented. CONCLUSION: There is a need to prepare national guidelines for vaccinating children with altered immunocompetence. Sharing vaccination practices by multidisciplinary vaccination units might increase and provide knowledge to develop national policies.

6.
Mol Biol Rep ; 50(10): 8551-8563, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37644370

RESUMEN

BACKGROUND: Liver cancer is the third leading cause of cancer-related deaths worldwide, and hepatocellular carcinoma (HCC) is the most common type of liver cancer. Transarterial interventions are among the chemotherapeutic approaches used in hardly operable regions prior to transplantation, and in electrochemotherapy, where doxorubicin is used. However, the efficacy of treatment is affected by resistance mechanisms. Previously, we showed that overexpression of the CUE5 gene results in doxorubicin resistance in Saccharomyces cerevisiae (S. cerevisiae). In this study, the effect of Toll-interacting protein (TOLLIP), the human ortholog of CUE5, on doxorubicin resistance was evaluated in HCC cells to identify its possible role in increasing the efficacy of transarterial interventions. METHODS AND RESULTS: The NIH Gene Expression Omnibus (GEO) and Oncomine datasets were analyzed for HCC cell lines with relatively low and high TOLLIP expression, and SNU449 and Hep3B cell lines were chosen, respectively. TOLLIP expression was increased by plasmid transfection and decreased by TOLLIP-siRNA in both cell lines and evaluated by RT-PCR and ELISA. Cell proliferation and viability were examined using xCELLigence and MTT assays after doxorubicin treatment, and growth inhibitory 50 (GI 50) concentrations were evaluated. Doxorubicin GI 50 concentrations decreased approximately 2-folds in both cell lines upon silencing TOLLIP after 48 h of drug treatment. CONCLUSIONS: Our results showed for the first time that silencing TOLLIP in hepatocellular carcinoma cells may help sensitize these cells to doxorubicin and increase the efficacy of chemotherapeutic regimens where doxorubicin is used.


Asunto(s)
Carcinoma Hepatocelular , Péptidos y Proteínas de Señalización Intracelular , Neoplasias Hepáticas , Humanos , Apoptosis , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Línea Celular Tumoral , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Resistencia a Antineoplásicos/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Saccharomyces cerevisiae , Péptidos y Proteínas de Señalización Intracelular/genética
7.
J Trace Elem Med Biol ; 79: 127222, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37270859

RESUMEN

Although boron is an essential element for many organisms, an excess amount of it can cause toxicity, and the mechanism behind this toxicity is not yet fully understood. The Gcn4 transcription factor plays a crucial role in the boron stress response by directly activating the expression of the boron efflux pump Atr1. More than a dozen transcription factors and multiple cell signaling pathways have roles in regulating the Gcn4 transcription factor under various circumstances. However, it is unknown which pathways or factors mediate boron signaling to Gcn4. Using the yeast Saccharomyces cerevisiae as a model, we analyzed the factors that converge on the Gcn4 transcription factor to assess their possible roles in boron stress signaling. Our findings show that the GCN system is activated by uncharged tRNA stress in response to boron treatment and that GCN1, which plays a role in transferring uncharged tRNAs to Gcn2, is necessary for the kinase activity of Gcn2. The SNF and PKA pathways were not involved in mediating boron stress, even though they interact with Gcn4. Mutations in TOR pathway genes, such as GLN3 and TOR1, abolished Gcn4 and ATR1 activation in response to boric acid treatment. Therefore, our study suggests that the TOR pathway must be functional to form a proper response against boric acid stress.


Asunto(s)
Proteínas de Saccharomyces cerevisiae , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas Quinasas/metabolismo , Boro/farmacología , Boro/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Saccharomyces cerevisiae/metabolismo , Factores de Transcripción/metabolismo , ARN de Transferencia/genética , ARN de Transferencia/metabolismo , Biosíntesis de Proteínas
8.
Neuroendocrinology ; 113(10): 1035-1050, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37321200

RESUMEN

INTRODUCTION: The aim of this study was to investigate how melatonin administration for 3 days or 7 days following cerebral ischemia (CI) injury would affect autophagy and, therefore, survival in neurons of the penumbra region. Moreover, it was also aimed at determining how this melatonin treatment would affect the neurological deficit score and rotarod and adhesive removal test durations. METHODS: Focal CI (90 min) was achieved in a total of 105 rats utilizing a middle cerebral artery occlusion model. After the start of reperfusion, the groups were treated with melatonin (10 mg/kg/day) for 3 days or 7 days. In all groups, neurological deficit scoring, rotarod, and adhesive removal tests were executed during reperfusion. Infarct areas were determined by TTC (2,3,5-triphenyltetrazolium chloride) staining at the end of the 3rd and 7th days of reperfusion. Beclin-1, LC3, p62, and caspase-3 protein levels were assessed using Western blot and immunofluorescence methods in the brain tissues. Moreover, penumbra areas were evaluated by transmission electron microscopy (TEM). RESULTS: Following CI, it was observed that melatonin treatment improved the rotarod and adhesive removal test durations from day 5 and reduced the infarct area after CI. It also induced autophagic proteins Beclin-1, LC3, and p62 and suppressed the apoptotic protein cleaved caspase-3. According to TEM findings, melatonin treatment partially reduced the damage in neurons after CI. CONCLUSION: Melatonin treatment following CI reduced the infarct area and induced the autophagic proteins Beclin-1, LC3, and p62 by inhibiting the apoptotic caspase-3 protein. The functional reflection of melatonin treatment on neurological test scores was became significant from the 5th day onward.


Asunto(s)
Lesiones Encefálicas , Isquemia Encefálica , Melatonina , Daño por Reperfusión , Ratas , Animales , Ratas Sprague-Dawley , Melatonina/farmacología , Melatonina/uso terapéutico , Caspasa 3 , Beclina-1 , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Autofagia/fisiología , Infarto , Infarto de la Arteria Cerebral Media/tratamiento farmacológico
9.
Leuk Lymphoma ; 64(7): 1304-1314, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37165575

RESUMEN

The St Jude Total Therapy Study XV was the first clinical trial to prospectively use minimal residual disease levels during and after remission induction therapy to guide risk-directed treatment. We used the Total Therapy XV protocol with minimal modification in treating 115 newly diagnosed pediatric acute lymphoblastic leukemia patients from low- and middle-income groups from January 2011 to December 2017. The mean age at diagnosis was 5.97 ± 3.96 years. The median follow-up period was 88 months. Three (2.6%) patients had bone marrow relapse, and one (0.87%) had an isolated central nervous system relapse. Nineteen of the patients (16.52%) died due to infection-related complications, three (2.61%) died due to progressive disease, and one (0.87%) died due to hematopoietic stem cell transplant complications. Five-year overall survival was 80%, and event-free survival was 78.3%. Our results showed that the Total XV treatment protocol could be used successfully in patients with ALL from low- and middle-income populations. However, infection-related deaths remain a significant problem.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Leucemia-Linfoma Linfoblástico de Células Precursoras , Niño , Humanos , Lactante , Preescolar , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Terapia Combinada , Recurrencia , Inducción de Remisión , Resultado del Tratamiento
10.
Diagnostics (Basel) ; 13(9)2023 Apr 28.
Artículo en Inglés | MEDLINE | ID: mdl-37174973

RESUMEN

BACKGROUND: The first aim of this study is to perform bioinformatic analysis of lncRNAs obtained from liver tissue samples from rats treated with cisplatin hepatotoxicity and without pathology. Another aim is to identify possible biomarkers for the diagnosis/early diagnosis of hepatotoxicity by modeling the data obtained from bioinformatics analysis with ensemble learning methods. METHODS: In the study, 20 female Sprague-Dawley rats were divided into a control group and a hepatotoxicity group. Liver samples were taken from rats, and transcriptomic and histopathological analyses were performed. The dataset achieved from the transcriptomic analysis was modeled with ensemble learning methods (stacking, bagging, and boosting). Modeling results were evaluated with accuracy (Acc), balanced accuracy (B-Acc), sensitivity (Se), specificity (Sp), positive predictive value (Ppv), negative predictive value (Npv), and F1 score performance metrics. As a result of the modeling, lncRNAs that could be biomarkers were evaluated with variable importance values. RESULTS: According to histopathological and immunohistochemical analyses, a significant increase was observed in the sinusoidal dilatation and Hsp60 immunoreactivity values in the hepatotoxicity group compared to the control group (p < 0.0001). According to the results of the bioinformatics analysis, 589 lncRNAs showed different expressions in the groups. The stacking model had the best classification performance among the applied ensemble learning models. The Acc, B-Acc, Se, Sp, Ppv, Npv, and F1-score values obtained from this model were 90%, 90%, 80%, 100%, 100%, 83.3%, and 88.9%, respectively. lncRNAs with id rna-XR_005492522.1, rna-XR_005492536.1, and rna-XR_005505831.1 with the highest three values according to the variable importance obtained as a result of stacking modeling can be used as predictive biomarker candidates for hepatotoxicity. CONCLUSIONS: Among the ensemble algorithms, the stacking technique yielded higher performance results as compared to the bagging and boosting methods on the transcriptomic data. More comprehensive studies can support the possible biomarkers determined due to the research and the decisive results for the diagnosis of drug-induced hepatotoxicity.

11.
Environ Sci Pollut Res Int ; 30(16): 47038-47051, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36735131

RESUMEN

Global warming and the ecological burden it causes affect people and the environment negatively and make adaptation difficult. For people to adapt to the environment and vice versa, they need to do extensive research and planning. Planning, on the other hand, is taking an easy form with the technology that has recently developed. GIS infrastructures and supporting satellite images along with software help with provincial-scale planning. This study has been handled on a scale covering the provincial borders of Nevsehir. The thermal data of the 10-year-old Landsat 7 satellite was analyzed and mapped in the Arc-GIS 10.2 package program. In the same way, maps of wind, air temperature, topography, and land use were created and the relationship between them was revealed by "Spearman's correlation" method. According to the results obtained, the average surface temperature in the study area was determined as 34.4 °C. When evaluated in terms of land use, natural grasslands have the highest surface temperature of 40.6 °C, while city structures have the highest average surface temperature of 33.3 °C. At the same time, the lowest surface temperature measured in the study area, 13.8 °C, is also found in natural grassland areas. A significant positive correlation was measured between the wind speed and the land use pattern, while a significant negative correlation emerged between the wind speed and the air temperature. In addition, there is another significant negative correlation between height and land surface temperature (LST). Furthermore, a high degree of positive significance was determined between altitude and wind speed. Finally, between air temperature and LST, a positive significance was observed.


Asunto(s)
Clima , Monitoreo del Ambiente , Temperatura , Urbanización , Niño , Humanos , Ciudades , Monitoreo del Ambiente/métodos , Calor
12.
Arch Physiol Biochem ; : 1-8, 2023 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-36645396

RESUMEN

INTRODUCTION: Glucose homeostasis is a physiological process mediated by a variety of hormones. Fibroblast growth factor (FGF) 21 is a protein expressed in the liver, adipose tissue, muscle and pancreas and exerts actions in multiple targets including adipose, liver, pancreas and hypothalamus. The aim of this study was to examine the possible involvement of FGF21 in pancreatic and central control of glucose by measuring reflective changes in the release of insulin and glucagon. METHODS: Thirty adult male Wistar Albino rats were divided; Control, PD + aCSF, PD + FGF21 groups (n = 10). Effects of intracerebroventricular (icv) FGF21 administration to pancreatic denervated (PD) rats. Agouti-related protein (AgRP), Pro-opiomelanocortin (POMC) levels and blood glucose homeostasis were investigated. RESULTS: Administration of FGF21 to 3rd ventricle increased food consumption but body weight didn't change significantly. AgRP level increased, pancreatic insulin levels increased, and glucagon level decreased. CONCLUSION: Central FGF21 administration is effective in regulating blood glucose homeostasis by increasing the amount and efficiency of insulin and changing glucose use.

13.
Braz. j. otorhinolaryngol. (Impr.) ; 88(supl.3): 25-33, Nov.-Dec. 2022. tab, graf
Artículo en Inglés | LILACS-Express | LILACS | ID: biblio-1420836

RESUMEN

Abstract Objective: Vestibular Migraine (VM) is the second most common cause in patients with vertigo. Patients with VM complain about vestibular symptoms during a headache attack or during the period between attacks. Vestibular Rehabilitation (VR), an exercised based therapy to treat dizziness and balance dysfunction has been shown to be effective in vestibular diseases. In this study, we aimed to assess the effect of VR for vestibular symptoms and quality of life in VM patients, and to compare the results with patients with vestibular disorders without migraine. Methods: Sixty (60) patients who received VR treatment were divided into two groups: vestibular migraine group (30 patients) and non-migraine vestibular dysfunction group (30 patients). All patients received VR for 18 sessions and the program was completed in 1.5 months. Preand post-treatment Dizziness Handicap Inventory (DHI) scores, Vestibular Disorders Activities of Daily Living Scale (VADL) scores, the frequency of dizziness and headache, and Computerized Dynamic Posturography (CDP) scores were assessed and compared retrospectively. Results: With VR in both the vestibular migraine group and vestibular dysfunction group, DHI score, VADL score, the frequency of dizziness and headache scores significantly impaired. Post-treatment CDP results were higher than pre- treatment results for both patient groups. Conclusion: With VR, a significant improvement was observed in subjective and objective balance assessment measurement. Vestibular Rehabilitation must be considered in patients who do not benefit from medical therapy or have limited benefit. Level of evidence: Level III (evidence obtained from well-designed controlled trials without randomization).

14.
Acta Otorhinolaryngol Ital ; 42(3): 281-286, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35880368

RESUMEN

Objective: The aim of this study is to evaluate vestibular functions with video head impulse test (VHIT) and to understand the value of VHIT in differential diagnosis in patients with vestibular migraine (VM) during dizziness attack. Materials and methods: Two groups were enrolled in this study. The first consisted of 84 vestibular migraine patients, and second group of 74 healthy subjects. VHIT was applied to patients with VM during vertigo attack and the results were compared with the VHIT values applied to subjects in the control group. Results: The mean vestibulo-ocular reflex (VOR) in all semicircular canals in the VM group was lower than healthy individuals, but the results were not statistically significant. Refixation saccades were found in 52.3% of VM patients and in 10.2% of healthy individuals. Conclusions: When patients with VM were evaluated with VHIT during vertiginous attack, VOR gain values were not different from healthy individuals, but the number of catch-up saccades were higher in VM patients, which indicates peripheral vestibular involvement. For differential diagnosis in patients with VM, vestibular tests should be performed during the vertigo attack. When evaluating VHIT results, the presence of refixation saccades should also be evaluated.


Asunto(s)
Prueba de Impulso Cefálico , Trastornos Migrañosos , Prueba de Impulso Cefálico/métodos , Humanos , Trastornos Migrañosos/complicaciones , Trastornos Migrañosos/diagnóstico , Reflejo Vestibuloocular , Canales Semicirculares , Vértigo/diagnóstico , Vértigo/etiología
16.
Microbiologyopen ; 11(3): e1284, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35765185

RESUMEN

Arsenic is a toxic metalloid that affects human health by causing numerous diseases and by being used in the treatment of acute promyelocytic leukemia. Saccharomyces cerevisiae (budding yeast) has been extensively utilized to elucidate the molecular mechanisms underlying arsenic toxicity and resistance in eukaryotes. In this study, we applied a genomic DNA overexpression strategy to identify yeast genes that provide arsenic resistance in wild-type and arsenic-sensitive S. cerevisiae cells. In addition to known arsenic-related genes, our genetic screen revealed novel genes, including PHO86, VBA3, UGP1, and TUL1, whose overexpression conferred resistance. To gain insights into possible resistance mechanisms, we addressed the contribution of these genes to cell growth, intracellular arsenic, and protein aggregation during arsenate exposure. Overexpression of PHO86 resulted in higher cellular arsenic levels but no additional effect on protein aggregation, indicating that these cells efficiently protect their intracellular environment. VBA3 overexpression caused resistance despite higher intracellular arsenic and protein aggregation levels. Overexpression of UGP1 led to lower intracellular arsenic and protein aggregation levels while TUL1 overexpression had no impact on intracellular arsenic or protein aggregation levels. Thus, the identified genes appear to confer arsenic resistance through distinct mechanisms but the molecular details remain to be elucidated.


Asunto(s)
Arsénico , Proteínas de Saccharomyces cerevisiae , Arsénico/metabolismo , Arsénico/toxicidad , Humanos , Agregado de Proteínas , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
18.
Funct Integr Genomics ; 22(3): 359-369, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35260975

RESUMEN

Congenital diaphragmatic hernia (CDH) is an anomaly characterized by a defect in the diaphragm, leading to the passage of intra-abdominal organs into the thoracic cavity. Herein, the presented work analyzes the global gene expression profiles in nine CDH and one healthy newborn. All of the patients had left posterolateral (Bochdalek) diaphragmatic hernia, operated via an abdominal approach, and stomach and bowels in the thorax cavity. Some patients also had additional anomalies. A total of 560 differentially regulated genes were measured. Among them, 11 genes showed significant changes in expression associated with lung tissue, vascular structure development, and vitamin A metabolism, which are typical ontologies related to CDH etiology. Among them, SLC25A24 and RAB3IL1 are involved in angiogenesis, HIF1A and FOXC2-AS1 are related with the alveolus, MAGI2-AS3 is associated with the diaphragm, LHX4 and DHH are linked with the lung, and BRINP1, FZD9, WNT4, and BLOC1S1-RDH5 are involved in retinol. Besides, the expression levels of some previously claimed genes with CDH etiology also showed diverse expression patterns in different patients. All these indicated that CDH is a complex, multigenic anomaly, requiring holistic approaches for its elucidation.


Asunto(s)
Hernias Diafragmáticas Congénitas , Diafragma , Perfilación de la Expresión Génica , Hernias Diafragmáticas Congénitas/genética , Hernias Diafragmáticas Congénitas/cirugía , Humanos , Recién Nacido , Análisis por Micromatrices , Proteínas del Tejido Nervioso
19.
J Int Adv Otol ; 18(1): 62-70, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35193848

RESUMEN

The current theory in physiopathology of benign paroxysmal positional vertigo is the mechanical theory, namely the cupulolithiasis-canalolithiasis theory. Repositioning maneuvers based on this theory has now taken place in therapy. However, mechanical theory is insufficient to explain some clinical situations and cannot fully enlighten the physiopathology. Mechanical theory is based on very few histological studies. Currently, these few articles are still used for reference. Anatomically, there are uncertainties that need to be explained in this theory. In this literature review, the histological and anatomical evidence is reviewed and the value of mechanical theory in benign paroxysmal positional vertigo physiopathology has been questioned. Studies suggest that the debris in the semicircular canals is caused by degeneration due to aging and may not be responsible for the symptoms in benign paroxysmal positional vertigo. Some patients with debris in semicircular canals do not have benign paroxysmal positional vertigo symptomatology, while some patients without debris may have benign paroxysmal positional vertigo symptomatology. Experimental and histological findings suggest that vestibulopathy due to inflammation caused by neurotropic viruses may lead to benign paroxysmal positional vertigo picture. For all these reasons, in benign paroxysmal positional vertigo physiopathology, there must be other factors besides particle debris in semicircular canals.


Asunto(s)
Vértigo Posicional Paroxístico Benigno , Membrana Otolítica , Vértigo Posicional Paroxístico Benigno/terapia , Humanos , Inflamación/patología , Posicionamiento del Paciente , Canales Semicirculares/patología
20.
Environ Sci Pollut Res Int ; 29(8): 11455-11468, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34536226

RESUMEN

Due to urbanization worldwide, gradual increase in construction and use of irregular urban topography affect urban climate negatively, triggering urban heat island (UHI) formations in cities and thereby causing them to become uninhabitable places for human comfort. This study, which covers the province of Diyarbakir in Turkey, aims to determine the spatial and temporal distribution of areas with potential urban heat island (UHI) by using remote sensing methods and satellite/terrain data available between 2001 and 2019. According to the Landsat 7 satellite, an area with a potential of 27.4 km2 in 2001, 20.8 km2 in 2006, 27.4 km2 in 2008, 16.7 km2 in 2010, and 12.2 km2 in 2012 was determined. According to the Landsat 8 satellite, it was measured as 14.49 km2 in 2017 and 15.67 km2 in 2018. According to Landsat 8 satellite data, areas with UHI potential increased by 14.6% over a 3-year period. According to Landsat 7 data, there has been a continuous fluctuation over the years. One of the important results of this study is that between 2001 and 2019, the higher the rate of change according to the surface temperature, the larger the area with the potential of the heat island. At the same time, it has been determined that spatially potential UHIs have a great potential not in the city center, but in the surrounding areas close to the center and in the topographically hollow areas.


Asunto(s)
Monitoreo del Ambiente , Calor , Ciudades , Temperatura , Turquía , Urbanización
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