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1.
Molecules ; 27(10)2022 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-35630584

RESUMO

The very large G-protein-coupled receptor 1 (VLGR1/ADGRV1) is the largest member of the adhesion G-protein-coupled receptor (ADGR) family. Mutations in VLGR1/ADGRV1 cause human Usher syndrome (USH), a form of hereditary deaf-blindness, and have been additionally linked to epilepsy. In the absence of tangible knowledge of the molecular function and signaling of VLGR1, the pathomechanisms underlying the development of these diseases are still unknown. Our study aimed to identify novel, previously unknown protein networks associated with VLGR1 in order to describe new functional cellular modules of this receptor. Using affinity proteomics, we have identified numerous new potential binding partners and ligands of VLGR1. Tandem affinity purification hits were functionally grouped based on their Gene Ontology terms and associated with functional cellular modules indicative of functions of VLGR1 in transcriptional regulation, splicing, cell cycle regulation, ciliogenesis, cell adhesion, neuronal development, and retinal maintenance. In addition, we validated the identified protein interactions and pathways in vitro and in situ. Our data provided new insights into possible functions of VLGR1, related to the development of USH and epilepsy, and also suggest a possible role in the development of other neuronal diseases such as Alzheimer's disease.


Assuntos
Proteômica , Receptores Acoplados a Proteínas G , Humanos , Receptores Acoplados a Proteínas G/metabolismo , Retina/metabolismo , Transdução de Sinais
2.
Adv Exp Med Biol ; 1039: 1-8, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-28801792

RESUMO

The use of electronic cigarettes or e-cigarettes is strongly on the rise. The literature confirms that in the process of quitting smoking using an electronic device dispensing nicotine should be a transitional stage before the complete cessation of smoking. The aim of the present study was to assess the popularity of e-cigarettes, the underlying reasons for use of such nicotine products, and the level of awareness of health hazards associated with e-cigarettes. The study is of a survey type. The material consisted of data collected from an anonymous survey distributed among 46 female and 23 male users of e-cigarettes in 2015. We used a questionnaire of our own design. The findings demonstrate that the main reason for a recourse to e-cigarettes is a desire to use fashionable technological innovations, and the conviction that such cigarettes are less harmful than the traditional tobacco products. Some respondents used e-cigarettes to quit smoking; others to minimize the harmful effects of smoking. Most respondents acquired information about e-cigarettes from friends or from the Internet. There was a high awareness of the chemical composition of substances contained in e-cigarettes. An interest in e-cigarettes is caused by an increased knowledge on the negative effects of traditional smoking. Currently, the e-cigarettes remains a technological novelty, so that the exact health effects of their long-term use are open to conjecture.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Conhecimentos, Atitudes e Prática em Saúde , Prevenção do Hábito de Fumar , Tabagismo , Adolescente , Adulto , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
3.
Bull Entomol Res ; 107(4): 543-549, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28330519

RESUMO

Insecticidal effects of the dichloromethane, ethyl acetate, acetone, ethanol and methanol extracts of Humulus lupulus (hops) L. cones and its principal components, xanthohumol was investigated on five stored pests, Sitophilus granarius (L.), Sitophilus oryzae (L.), Acanthoscelides obtectus (Say.), Tribolium castaneum (Herbst) and Lasioderma serricorne (F.). The mortality of adults of the insects treated with 2, 5, 5, 10 and 20 mg mlÌ -1 concentrations of the extracts and xanthuhumol was counted after 24, 48, 72, 96 and 120 h. In order to determine the toxic effects of the substances tested against all tested insects, durations for 50% mortality of the adults, and LD50 values were also determined in the first 48 h by probit analysis. Our results also showed that xanthohumol was more toxic against the pests in comparison with the extracts applications. LD50 values for xanthohumol were found to be low dose as compared with the extracts. Xanthohumol was more toxic against S. granarius (L.) with 6.8 µg of LD50 value. Among the extracts, methanol extract was less effective than other extracts against all tested insects. The ethyl acetate extract of H. lupulus cones was the most effective extract against the tested pests. The quantitative amounts of xanthohumol in the extracts were determined using a high-performance liquid chromatography. The quantitative data indicated that amount of xanthohumol in the extracts increased with increase of polarity of the solvents used from methanol to dichloromethane. The methanol extract contained the high amount of xanthohumol with 5.74 g/100 g extract (0.46 g/100 g plant sample).


Assuntos
Flavonoides , Humulus/química , Inseticidas/análise , Propiofenonas , Tribolium , Gorgulhos , Animais , Parasitologia de Alimentos , Dose Letal Mediana , Malation , Extratos Vegetais/química
4.
Adv Exp Med Biol ; 885: 39-46, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26801152

RESUMO

Smoking cigarettes negatively influences the functioning of the body. Among other effects, it has an important impact on the respiratory system, circulation, and behavior. It leads to morphological and physiological changes in organs and tissues, so it can change mood. The aim of this study was to assess the relationships between tobacco abuse and self-assessment of health. The survey was conducted among Polish (243) and foreign (80) medical students at the Pomeranian Medical University in Szczecin, Poland. The study was based on a survey questionnaire of the authors' own design, comprising open and multi-choice questions. Our questionnaire was based on the international standard questionnaire from the Health Behavior in School-Aged Children study (Currie et al. 2009). 80 % of students surveyed were free of any chronic diseases. The results showed that only 23 % of the women and 20 % of the men assessed their health as very good, over 60 % as good, and the remaining at lower levels. We did not observe significant differences between smokers and non-smokers. Physical activity in both groups was generally assessed as good or sufficient. We did not observe significant differences between groups in the incidence of headache, abdominal pain, or vertigo. Significant differences were found in the intake of painkillers.


Assuntos
Nível de Saúde , Autoavaliação (Psicologia) , Tabagismo/fisiopatologia , Comportamentos Relacionados com a Saúde , Humanos , Estudantes de Medicina , Inquéritos e Questionários , Tabagismo/psicologia
5.
Adv Exp Med Biol ; 2016 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-27966111

RESUMO

Concha bullosa is a variant of the sinonasal anatomy in which the middle nasal turbinate contains pneumatized cells, which leads to turbinate enlargement. The reason for concha bullosa formation is unclear, but the variant is seen in up to half the modern population and it may predispose to paranasal sinusitis. The variant has hitherto featured little in paleopathology. Therefore, in the present study we seek to determine the presence of concha bullosa, with the coexisting hypertrophy of the middle turbinate and signs of sinusitis or other pathology of the paranasal complex, in a population living in Tomersdorf-Toporow in the Upper Lausatia, a historical region in Germany and Poland, presently Zgorzelec County in the Lower Silesian voivodeship, at the turn of the nineteenth and twentieth century. The material consisted of 32 skeletons (24 males, 8 females). The gender, age, and stress indicators and the presence of pathological signs were assessed, followed by CT of the skulls. We found 2 skulls (6.3 %) with concha bullosa. In one case septal nasal deviation was present. We conclude that the incidence of concha bullosa could be lower in the past times than at present. Wider research is necessary to settle whether concha bullosa is indeed a rare respiratory paleopathology or a missed, and thus underreported observation.

6.
Adv Exp Med Biol ; 952: 65-73, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27614624

RESUMO

Concha bullosa is a variant of the sinonasal anatomy in which the middle nasal turbinate contains pneumatized cells, which leads to turbinate enlargement. The reason for concha bullosa formation is unclear, but the variant is seen in up to half the modern population and it may predispose to paranasal sinusitis. The variant has hitherto featured little in paleopathology. Therefore, in the present study we seek to determine the presence of concha bullosa, with the coexisting hypertrophy of the middle turbinate and signs of sinusitis or other pathology of the paranasal complex, in a population living in Tomersdorf-Toporow in the Upper Lausatia, a historical region in Germany and Poland, presently Zgorzelec County in the Lower Silesian voivodeship, at the turn of the nineteenth and twentieth century. The material consisted of 32 skeletons (24 males, 8 females). The gender, age, and stress indicators and the presence of pathological signs were assessed, followed by CT of the skulls. We found 2 skulls (6.3 %) with concha bullosa. In one case septal nasal deviation was present. We conclude that the incidence of concha bullosa could be lower in the past times than at present. Wider research is necessary to settle whether concha bullosa is indeed a rare respiratory paleopathology or a missed, and thus underreported observation.


Assuntos
Septo Nasal/anormalidades , Sinusite/diagnóstico , Crânio/anormalidades , Conchas Nasais/anormalidades , Feminino , Alemanha , Humanos , Masculino , Septo Nasal/diagnóstico por imagem , Paleopatologia/métodos , Polônia , Sinusite/diagnóstico por imagem , Crânio/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Conchas Nasais/diagnóstico por imagem
7.
Adv Exp Med Biol ; 858: 79-85, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26017723

RESUMO

Sudden balance disorders with violent vegetative symptoms (nausea and vomiting) pose a diagnostic and therapeutic problem. In children vertigo/dizziness with symptoms of vestibular dysfunction is rare, but as vascular etiology is unlikely in children such symptoms arouse concern. This article presents two cases of this type of vertigo. The patients were two boys (6 and 9 years old). They came down with similar symptoms: sudden dizziness, disabled walking, nausea and vomiting, spontaneous nystagmus, and a positive Romberg test. The onset of the balance disorder was preceded by respiratory infection: common cold with symptoms of inflammation of the mucous membrane in the nose and throat. Laboratory tests revealed increased levels of C-reactive protein only in the older boy. Neuroinfection and a displacement process were ruled out. Videonystagmography revealed vestibular dysfunction and vestibular neuronitis on the left side.


Assuntos
Nistagmo Patológico/fisiopatologia , Infecções Respiratórias/fisiopatologia , Vertigem/fisiopatologia , Neuronite Vestibular/fisiopatologia , Proteína C-Reativa/metabolismo , Criança , Humanos , Masculino , Náusea/fisiopatologia , Nistagmo Patológico/sangue , Nistagmo Patológico/diagnóstico , Nistagmo Patológico/etiologia , Infecções Respiratórias/sangue , Infecções Respiratórias/complicações , Infecções Respiratórias/diagnóstico , Vertigem/sangue , Vertigem/diagnóstico , Vertigem/etiologia , Neuronite Vestibular/sangue , Neuronite Vestibular/diagnóstico , Neuronite Vestibular/etiologia , Vômito/fisiopatologia
8.
Adv Exp Med Biol ; 873: 35-41, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26318297

RESUMO

The most common diseases of the upper respiratory tract in children treated by ear-nose-throat (ENT) specialists in ambulatory practice are infections, such as colds, rhinitis, sinusitis and pharyngitis, very frequently accompanied and promoted by chronic nasal obstructions of various etiology. These diseases, when treated incorrectly or for too long, cause frequent school absenteeism and may also lead to hearing disorders linked with acute or suppurative otitis. They may also habitually perpetuate abnormal breathing and result in occlusal disorders. The aim of this study was to assess the incidence and type of upper respiratory tract diseases in children, depending on age and sex of patients and on the seasons. We also discussed the role of the ENT specialist in the diagnosis and treatment of certain diseases. In the study we analyzed the medical records of patients of preschool and school age treated in the ENT outpatient clinic over one calendar year. It was found that the largest group of patients comprised children of 3-7 years of age, and most children visited the outpatient clinic in the period March-May. The most common main disorder, according to ICD-10, was acute nasopharyngitis (J00) and vasomotor and allergic rhinitis (J30). Among the comorbid disorders H65 and H66 were the most frequent. No significant gender differences were noted in the frequency of particular types of disease.


Assuntos
Otolaringologia , Doenças Respiratórias/epidemiologia , Infecções Respiratórias/epidemiologia , Adolescente , Fatores Etários , Assistência Ambulatorial , Criança , Pré-Escolar , Registros Eletrônicos de Saúde , Feminino , Humanos , Lactente , Classificação Internacional de Doenças , Masculino , Nasofaringite/epidemiologia , Polônia/epidemiologia , Respiração , Doenças Respiratórias/terapia , Infecções Respiratórias/terapia , Rinite Alérgica Perene/epidemiologia , Rinite Vasomotora/epidemiologia , Fatores Sexuais
9.
Adv Exp Med Biol ; 755: 189-94, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22826066

RESUMO

Research suggests that reducing the degree of nicotine addiction in the population cannot be achieved only by prevention programs. Legislative measures are necessary to be taken by the state. The aim of this study was to assess the degree of tobacco abuse in three groups of students. It also assesses the influence of ban on smoking in public places on passive contact of students with tobacco. A customized survey made up of open and closed questions was conducted among 102 students of electrical faculty, 109 medical students, and 71 students of animal husbandry faculty. The results showed that significantly more women from the electrical faculty smoked. Among the students of animal husbandry, men smoke significantly more cigarettes than women. Women studying animal husbandry start smoking significantly earlier (by about 2 years) than women from other faculties. They are also significantly less likely to smoke cigarettes at school and at home. According to the study, the Polish law to ban smoking in public places, in force since the 15th of November 2010, did not make students quit smoking, although the rate of smoking students decreased. Students did not observe restrictions on smoking in their environment. The study indicates a positive influence of the anti-nicotine legislation on passive smoking, just after 3 months from its introduction.


Assuntos
Fumar/epidemiologia , Fumar/legislação & jurisprudência , Estudantes/estatística & dados numéricos , Poluição por Fumaça de Tabaco , Adolescente , Adulto , Criação de Animais Domésticos , Criança , Feminino , Humanos , Masculino , Estudantes de Medicina
10.
Adv Exp Med Biol ; 755: 169-77, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22826064

RESUMO

ß2-adrenergic receptors re abundantly expressed in airways, which explains the role of ß2 agonists, the strongest bronchodilators, in treatment of bronchial constriction. There may be a relation between ß2ADR gene polymorphism and the response to treatment with ß2 agonists. In the present study we attempted to study these relationship in vivo, estimating spirometric values before and after the use of salbutamol in reference to variant of ß2ADR gene polymorphisms. The study involved 148 healthy male volunteers. After the examination of the gene polymorphism of the ß2-adrenergic receptor (ß2-ADR) at nucleotide positions 46 and 79 (g.46 and g.79) we performed spirometry testing in all subjects. The pulmonary function was checked twice a day; before and 15 min after the administration of salbutamol. All subjects had normal basic values of spirometry. The use of salbutamol significantly increased spirometric values in all groups determined by ß2ADR gene polymorphisms. Analysis of the spirometric values in individual groups showed a significant increase only in peak expiratory flow (g.46AA and g.79CC). The results of this study give an insight into a possibly important mechanism of the response to treatment with ß2-agonists.


Assuntos
Albuterol/uso terapêutico , Broncodilatadores/uso terapêutico , Polimorfismo Genético , Receptores Adrenérgicos beta 2/genética , Volume Expiratório Forçado , Humanos , Masculino , Espirometria , Capacidade Vital
11.
Basic Clin Pharmacol Toxicol ; 133(4): 313-330, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37002809

RESUMO

VLGR1/ADGRV1 (very large G protein-coupled receptor-1) is the largest known adhesion G protein-coupled receptor. Mutations in VLGR1/ADGRV1 cause Usher syndrome (USH), the most common form of hereditary deaf-blindness, and have been additionally linked to epilepsy. Although VLGR1/ADGRV1 is almost ubiquitously expressed, little is known about the subcellular function and signalling of the VLGR1 protein and thus about mechanisms underlying the development of diseases. Using affinity proteomics, we identified key components of autophagosomes as putative interacting proteins of VLGR1. In addition, whole transcriptome sequencing of the retinae of the Vlgr1/del7TM mouse model revealed altered expression profiles of gene-related autophagy. Monitoring autophagy by immunoblotting and immunocytochemistry of the LC3 and p62 as autophagy marker proteins revealed evoked autophagy in VLGR1-deficient hTERT-RPE1 cells and USH2C patient-derived fibroblasts. Our data demonstrate the molecular and functional interaction of VLGR1 with key components of the autophagy process and point to an essential role of VLGR1 in the regulation of autophagy at internal membranes. The close association of VLGR1 with autophagy helps to explain the pathomechanisms underlying human USH and epilepsy related to VLGR1 defects.


Assuntos
Epilepsia , Receptores Acoplados a Proteínas G , Síndromes de Usher , Animais , Humanos , Camundongos , Autofagia , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais , Síndromes de Usher/genética , Síndromes de Usher/metabolismo
12.
Basic Clin Pharmacol Toxicol ; 133(4): 301-312, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36929698

RESUMO

VLGR1/ADGRV1 (very large G protein-coupled receptor-1) is the largest adhesion G protein-coupled receptor (aGPCR). Mutations in VLGR1/ADGRV1 are associated with human Usher syndrome, the most common form of deaf-blindness, and also with epilepsy in humans and mice. VLGR1 is expressed almost ubiquitously but is mainly found in the CNS and in the sensory cells of the eye and inner ear. Little is known about the pathogenesis of the diseases related to VLGR1. We previously identified VLGR1 as a vital component of focal adhesions (FAs) serving as a metabotropic mechanoreceptor controls cell spreading and migration. FAs are highly dynamic and turnover in response to internal and external signals. Here, we aimed to elucidate how VLGR1 participates in FA turnover. Nocodazole washouts and live cell imaging of paxillin-DsRed2 consistently showed that FA disassembly was not altered, but de novo assembly of FA was significantly delayed in Vlgr1-deficient astrocytes, indicating that VLGR1 is enrolled in FA assembly. In FRAP experiments, recovery rates were significantly reduced in Vlgr1-deficient FAs, indicating reduced turnover kinetics in VLGR1-deficient FAs. We showed that VLGR1 regulates cell migration by controlling the FA turnover during their assembly and expect novel insights into pathomechanisms related to pathogenic dysfunctions of VLGR1.


Assuntos
Astrócitos , Adesões Focais , Animais , Humanos , Camundongos , Paxilina/genética , Paxilina/metabolismo , Adesões Focais/genética , Adesões Focais/metabolismo , Astrócitos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Movimento Celular
13.
Front Cell Dev Biol ; 11: 1199069, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37427378

RESUMO

The human Usher syndrome (USH) is the most common form of a sensory hereditary ciliopathy characterized by progressive vision and hearing loss. Mutations in the genes ADGRV1 and CIB2 have been associated with two distinct sub-types of USH, namely, USH2C and USH1J. The proteins encoded by the two genes belong to very distinct protein families: the adhesion G protein-coupled receptor ADGRV1 also known as the very large G protein-coupled receptor 1 (VLGR1) and the Ca2+- and integrin-binding protein 2 (CIB2), respectively. In the absence of tangible knowledge of the molecular function of ADGRV1 and CIB2, pathomechanisms underlying USH2C and USH1J are still unknown. Here, we aimed to enlighten the cellular functions of CIB2 and ADGRV1 by the identification of interacting proteins, a knowledge that is commonly indicative of cellular functions. Applying affinity proteomics by tandem affinity purification in combination with mass spectrometry, we identified novel potential binding partners of the CIB2 protein and compared these with the data set we previously obtained for ADGRV1. Surprisingly, the interactomes of both USH proteins showed a high degree of overlap indicating their integration in common networks, cellular pathways and functional modules which we confirmed by GO term analysis. Validation of protein interactions revealed that ADGRV1 and CIB2 mutually interact. In addition, we showed that the USH proteins also interact with the TRiC/CCT chaperonin complex and the Bardet Biedl syndrome (BBS) chaperonin-like proteins. Immunohistochemistry on retinal sections demonstrated the co-localization of the interacting partners at the photoreceptor cilia, supporting the role of USH proteins ADGRV1 and CIB2 in primary cilia function. The interconnection of protein networks involved in the pathogenesis of both syndromic retinal dystrophies BBS and USH suggest shared pathomechanisms for both syndromes on the molecular level.

14.
Artigo em Inglês | MEDLINE | ID: mdl-35882591

RESUMO

INTRODUCTION AND AIMS: Cystic fibrosis (CF) is a genetic disease whose gastrointestinal compromise mainly involves the pancreas, bile ducts, and liver. Our aim was to analyze abdominal ultrasound findings. METHODS: A retrospective, descriptive study was conducted on adults (patients ≥ 16 years of age) diagnosed with CF, within the time frame of 2006-2019. Clinical and genetic parameters, body mass index, forced expiratory volume in one second, pancreatic insufficiency, CF-related diabetes, cirrhosis secondary to CF, and abdominal ultrasound images were analyzed. RESULTS: Seventy patients, 39 of whom were men (55.8%), had a mean age of 27 years and a mean body mass index of 21.3 ± 2.8 kg/m2 (r: 17-30.9). Forty-seven (67.1%) presented with pancreatic insufficiency, 6 (8.5%) with cirrhosis secondary to CF, and 21 (30%) had CF-related diabetes. Median forced expiratory volume in one second was 47% and the F508del mutation was found in 56.1%. Images of the pancreas: no pathologic findings in 49 (70%), increased echogenicity in 18 (25.7%), and cysts in 3 (4.3%). Gallbladder images: microgallbladder in 3 (4.2%), biliary sludge in 2 (2.8%), gallstones in 7 (10%), and a history of cholecystectomy in 4 (5.8%). Liver and spleen images: no pathologic findings in 47 (67.2%), homogeneous hepatomegaly with splenomegaly in 2 (2.8%), a heterogeneous pattern of the parenchyma in 11 (15.8%), increased echogenicity in 4 (5.7%), and heterogeneous echo patterns, lobulated liver contour, and splenomegaly in 6 (8.5%). CONCLUSION: Abdominal ultrasound is a safe, low-cost technique that enables the identification of some degree of chronic liver and pancreatic diseases, improving the approach and follow-up decisions in adult patients with CF.

15.
Eur J Clin Microbiol Infect Dis ; 30(6): 727-31, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21416216

RESUMO

Trichophyton rubrum represents the most frequently isolated causative agent of superficial dermatophyte infections. Several genotyping methods have recently been introduced to improve the delineation between pathogenic fungi at both the species and the strain levels. The purpose of this study was to apply selected DNA fingerprinting methods to the identification and strain discrimination of T. rubrum clinical isolates. Fifty-seven isolates from as many tinea patients were subjected to species identification by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analysis and strain differentiation using a randomly amplified polymorphic DNA (RAPD) method, with two primers designated 1 and 6. Using PCR-RFLP, 55 of the isolates studied were confirmed to be T. rubrum. Among those, a total of 40 and five distinct profiles were obtained by RAPD with primers 1 and 6, respectively. The combination of profiles from both RAPD assays resulted in 47 genotypes and an overall genotypic diversity rate of 85.4%. A dendrogram analysis performed on the profiles generated by RAPD with primer 1 showed most of the isolates (87.3%) to be genetically related. PCR-RFLP serves as a rapid and reliable method for the identification of T. rubrum species, while the RAPD analysis is rather a disadvantageous tool for T. rubrum strain typing.


Assuntos
Técnicas de Tipagem Micológica/métodos , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição , Técnica de Amplificação ao Acaso de DNA Polimórfico/métodos , Tinha/microbiologia , Trichophyton/classificação , Trichophyton/isolamento & purificação , Impressões Digitais de DNA/métodos , Humanos , Trichophyton/genética
16.
J Mycol Med ; 31(1): 101082, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33249314

RESUMO

Invasive candidiasis (IC) is a life-threatening fungal infection with high morbidity and mortality. In this study, we aimed to investigate the Candida species distribution and antifungal drug susceptibility and to identify the risk factors associated with IC mortality in children. We conducted a retrospective, single-centre study of paediatric IC in patients from a tertiary care hospital in Turkey between January 2013 and February 2019. A total of 56 Candida isolates underwent antifungal susceptibility testing performed by Sensititre YeastOne YO10 panel, and the demographic and clinical data of 65 patients were examined during the study period. The most commonly isolated species was Candida albicans in 30 patients (46%), followed by C. parapsilosis in 25 patients (38%) and C. tropicalis in three patients (5%). According to the antifungal drug susceptibility testing, C. albicans was fully susceptible to fluconazole and the other antifungal agents (100%). None of the isolates displayed resistance to anidulafungin, micafungin, flucytosine, posaconazole, voriconazole or itraconazole. There were low rates of resistance to fluconazole (1.8%), caspofungin (1.8%) and micafungin (1.8%). In addition, 5.3% of the Candida isolates were susceptible in a dose-dependent manner to itraconazole, 3.6% were susceptible to voriconazole and fluconazole and 1.8% were susceptible to anidulafungin. The mortality rate of IC was 15.4%. Thrombocytopenia after IC treatment was significantly associated with mortality in the multivariate analysis. These results, which help determine the species distribution, antifungal susceptibility patterns and risk factors for mortality, could make a significant contribution to the management of these challenging infections, including choosing appropriate empirical antifungal therapy.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/patogenicidade , Candidíase Invasiva/mortalidade , Adolescente , Antifúngicos/uso terapêutico , Candida/classificação , Candidíase Invasiva/tratamento farmacológico , Criança , Pré-Escolar , Farmacorresistência Fúngica Múltipla , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Fatores de Risco , Centros de Atenção Terciária/estatística & dados numéricos , Turquia
17.
STAR Protoc ; 2(4): 100954, 2021 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-34917973

RESUMO

Primary astrocytes have gained attention as an important model for in vitro biological and biochemical research in the last decades. In this protocol, we describe a fast and cost-effective technique for isolating, culturing, and maintaining primary mouse astrocytes at ∼ 80% purity levels, which can be used in in vitro studies for migration and focal adhesion dynamics. In addition, we present an optimized transfection and manual quantification approach for focal adhesion analysis in fixed and living cells. For complete details on the use and execution of this protocol, please refer to Kusuluri et al. (2021).


Assuntos
Astrócitos , Técnicas de Cultura de Células/métodos , Separação Celular/métodos , Adesões Focais/fisiologia , Animais , Astrócitos/citologia , Astrócitos/fisiologia , Adesão Celular/fisiologia , Movimento Celular/fisiologia , Células Cultivadas , Camundongos
18.
iScience ; 24(4): 102283, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33851099

RESUMO

VLGR1 (very large G protein-coupled receptor-1) is by far the largest adhesion G protein-coupled receptor in humans. Homozygous pathologic variants of VLGR1 cause hereditary deaf blindness in Usher syndrome 2C and haploinsufficiency of VLGR1 is associated with epilepsy. However, its molecular function remains elusive. Herein, we used affinity proteomics to identify many components of focal adhesions (FAs) in the VLGR1 interactome. VLGR1 is localized in FAs and assembles in FA protein complexes in situ. Depletion or loss of VLGR1 decreases the number and length of FAs in hTERT-RPE1 cells and in astrocytes of Vlgr1 mutant mice. VLGR1 depletion reduces cell spread and migration kinetics as well as the response to mechanical stretch characterizing VLGR1 as a metabotropic mechanosensor in FAs. Our data reveal a critical role of VLGR1 in the FA function and enlighten potential pathomechanisms in diseases related to VLGR1.

19.
Eur J Med Res ; 15 Suppl 2: 36-40, 2010 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-21147617

RESUMO

BACKGROUND: Breathing-related sleep disorders cover several conditions (isolated snoring, UARS - upper airway resistance syndrome, obstructive sleep apnea, hypopnea, obesity hypoventilation syndrome) characterized by a variety of symptoms and complex etiology. The conditions can be successfully treated in most cases. Excessive body mass is a factor increasing the probability of the disorders. In most patients it is the only reason for breathing-related sleep disorders. However, it often coexists with various anatomical abnormalities in the upper airway, endocrinological diseases or genetic defects of the facial skeleton, and occurs more frequently in older people, especially men. Excessive body mass significantly affects the range and success of the treatment. OBJECTIVE: To analyze treatment outcome in patients treated at the otolaryngology unit for snoring and related diseases with submucosal tissue reduction within the nasal cavity, pharynx, and soft palate. MATERIAL AND METHODS: Patients were stratified into three study groups depending on the body mass index (BMI): normal, overweight, and obese. The BMI value was compared to the severity of breathing disorders during sleep, with the incidence of other systemic diseases (e.g., hypertension, diabetes), and with treatment outcome. RESULTS AND CONCLUSIONS: The analysis demonstrated a significant influence of body mass on snoring, particularly in complicated and severe types of breathing disorders, such obstructive sleep apnea or hypopnea, and the obesity hypoventilation syndrome. Corrective interventions carried out to eliminate anatomical abnormalities causing obstruction of upper airways provided the best therapeutic effects in patients with normal body mass.


Assuntos
Índice de Massa Corporal , Síndromes da Apneia do Sono/terapia , Ronco/terapia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
Eur J Med Res ; 15 Suppl 2: 135-40, 2010 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-21147641

RESUMO

INTRODUCTION: The vagus nerve plays a special role in the control of respiratory system activity which represents the parasympathetic part of the autonomic nervous system. A small bronchial innervation by the sympathetic system also is observed, and there is a significant expression of adrenergic receptors, in particular ß⊂2 receptors, in the airways. The development of genetics and molecular biology allows for a detailed study which can clarify the essential elements in the pathogenesis of many types of lung disease, as well as the physiological phenomena - bronchial smooth muscle tone and their contractile mechanism. MATERIAL AND METHODS: The study involved 148 healthy male volunteers aged 20-26. In all subjects, gene polymorphism at nucleotide position 46 and 79 of ß⊂2-adrenergic receptor (ß⊂2-ADR) was assessed. According to the gene polymorphism data, we divided the whole examined population of males into 6 groups for further studies. Moreover, in all the subjects, we performed spirometry testing to verify their pulmonary functions. RESULTS: The basic values of spirometry tests in all subjects were in the range of normal values. The frequency of different genotypes in the gene polymorphism of the ß⊂2-adrenergic receptor at nucleotide positions 46 and 79 were typical for the Caucasian population. Analysis of the output values of spirometry, conducted in the particular groups based on their genotype, showed significant inter-group differences in the selected spirometry tests. CONCLUSIONS: Our results may be useful in explaining the differences in the measured values of spirometric indices in healthy subjects in relation to the polymorphism of ß⊂2-ADR, and may also contribute to the verification of standards for spirometric indices for this selected group of young males in the Polish population.


Assuntos
Pulmão/fisiologia , Polimorfismo Genético , Receptores Adrenérgicos beta 2/genética , Adulto , Volume Expiratório Forçado , Genótipo , Humanos , Masculino , Receptores Adrenérgicos beta 2/química , Espirometria , Capacidade Vital
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