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1.
Artículo en Inglés | MEDLINE | ID: mdl-38749844

RESUMEN

PURPOSE: The ultrasound specialists face a substantial issue with work-related musculoskeletal disorders (WMSDs), characterized by occupation-related pain, reaching an estimated frequency of up to 90.5%. The type and location of pain vary depending on the sonographers specialty and the specific anatomical areas being examined. Our study aimed to assess the prevalence and intensity of pain among Polish doctors from various specialties conducting ultrasound examinations. MATERIALS AND METHODS: The study has been performed between July and December 2023, involving 90 participants (51.9% women) actively practicing ultrasound diagnostics. The data collection process utilized a structured questionnaire developed by the researchers for this study. The questionnaire covered personal factors, including gender and age, and work-related aspects like workplace, specialty, sonography experience, and the types of examinations conducted. Statistical analysis involved both descriptive statistics and correlation analysis. RESULTS: The age distribution ranged from 26 to 74 years, with mean (SD) of 43.1 (12.2) years. The leading specialties among physicians were radiology (22.2%) and internal medicine (22.2%). Among all physicians, 65.6% reported pain during or after ultrasound scans, with a mean (SD) pain intensity of 6.17 (2) in a 1-10 scale. The analysis indicated no correlation between age and gender and the occurrence of discomfort. CONCLUSIONS: WMSDs pose a significant risk to Polish sonographers, especially those specializing in vascular surgery, general surgery and obstetrics and gynecology specialties. The study underscores a notable deficit, with only 10% of the personnel reporting training in ergonomics for ultrasound work.

2.
Int J Mol Sci ; 22(24)2021 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-34948248

RESUMEN

The bacterial proteins of the Dsb family catalyze the formation of disulfide bridges between cysteine residues that stabilize protein structures and ensure their proper functioning. Here, we report the detailed analysis of the Dsb pathway of Campylobacter jejuni. The oxidizing Dsb system of this pathogen is unique because it consists of two monomeric DsbAs (DsbA1 and DsbA2) and one dimeric bifunctional protein (C8J_1298). Previously, we showed that DsbA1 and C8J_1298 are redundant. Here, we unraveled the interaction between the two monomeric DsbAs by in vitro and in vivo experiments and by solving their structures and found that both monomeric DsbAs are dispensable proteins. Their structures confirmed that they are homologs of EcDsbL. The slight differences seen in the surface charge of the proteins do not affect the interaction with their redox partner. Comparative proteomics showed that several respiratory proteins, as well as periplasmic transport proteins, are targets of the Dsb system. Some of these, both donors and electron acceptors, are essential elements of the C. jejuni respiratory process under oxygen-limiting conditions in the host intestine. The data presented provide detailed information on the function of the C. jejuni Dsb system, identifying it as a potential target for novel antibacterial molecules.


Asunto(s)
Oxidorreductasas/metabolismo , Proteínas Periplasmáticas/metabolismo , Proteína Disulfuro Isomerasas/genética , Proteína Disulfuro Isomerasas/metabolismo , Secuencia de Aminoácidos , Fenómenos Fisiológicos Bacterianos , Proteínas Bacterianas/metabolismo , Campylobacter jejuni/patogenicidad , Campylobacter jejuni/fisiología , Disulfuros/metabolismo , Oxidación-Reducción , Oxidorreductasas/genética , Periplasma/metabolismo , Proteínas Periplasmáticas/genética , Homología de Secuencia de Aminoácido
3.
PLoS One ; 15(3): e0230366, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32203539

RESUMEN

Posttranslational generation of disulfide bonds catalyzed by bacterial Dsb (disulfide bond) enzymes is essential for the oxidative folding of many proteins. Although we now have a good understanding of the Escherichia coli disulfide bond formation system, there are significant gaps in our knowledge concerning the Dsb systems of other bacteria, including Campylobacter jejuni, a food-borne, zoonotic pathogen. We attempted to gain a more complete understanding of the process by thorough analysis of C8J_1298 functioning in vitro and in vivo. C8J_1298 is a homodimeric thiol-oxidoreductase present in wild type (wt) cells, in both reduced and oxidized forms. The protein was previously described as a homolog of DsbC, and thus potentially should be active in rearrangement of disulfides. Indeed, biochemical studies with purified protein revealed that C8J_1298 shares many properties with EcDsbC. However, its activity in vivo is dependent on the genetic background, namely, the set of other Dsb proteins present in the periplasm that determine the redox conditions. In wt C. jejuni cells, C8J_1298 potentially works as a DsbG involved in the control of the cysteine sulfenylation level and protecting single cysteine residues from oxidation to sulfenic acid. A strain lacking only C8J_1298 is indistinguishable from the wild type strain by several assays recognized as the criteria to determine isomerization or oxidative Dsb pathways. Remarkably, in C. jejuni strain lacking DsbA1, the protein involved in generation of disulfides, C8J_1298 acts as an oxidase, similar to the homodimeric oxidoreductase of Helicobater pylori, HP0231. In E. coli, C8J_1298 acts as a bifunctional protein, also resembling HP0231. These findings are strongly supported by phylogenetic data. We also showed that CjDsbD (C8J_0565) is a C8J_1298 redox partner.


Asunto(s)
Campylobacter jejuni/enzimología , Disulfuros/metabolismo , Proteínas Periplasmáticas/metabolismo , Proteína Disulfuro Reductasa (Glutatión)/metabolismo , Secuencia de Aminoácidos , Campylobacter jejuni/genética , Escherichia coli/enzimología , Escherichia coli/genética , Helicobacter pylori/enzimología , Helicobacter pylori/genética , Oxidación-Reducción , Periplasma/enzimología , Proteínas Periplasmáticas/genética , Filogenia , Proteína Disulfuro Reductasa (Glutatión)/genética
4.
Crit Rev Microbiol ; 45(4): 433-450, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31190593

RESUMEN

The Dsb protein family in prokaryotes catalyzes the generation of disulfide bonds between thiol groups of cysteine residues in nascent proteins, ensuring their proper three-dimensional structure; these bonds are crucial for protein stability and function. The first Dsb protein, Escherichia coli DsbA, was described in 1991. Since then, many details of the bond-formation process have been described through microbiological, biochemical, biophysical and bioinformatics strategies. Research with the model microorganism E. coli and many other bacterial species revealed an enormous diversity of bond-formation mechanisms. Research using Dsb protein engineering has significantly helped to reveal details of the disulfide bond formation. The first part of this review presents the research that led to understanding the mechanism of action of DsbA proteins, which directly transfer their own disulfide into target proteins. The second part concentrates on the mechanism of electron transport through the cell cytoplasmic membrane. Third and lastly, the review discusses the contribution of this research towards new antibacterial agents.


Asunto(s)
Biotecnología/métodos , Disulfuros/metabolismo , Proteína Disulfuro Isomerasas/genética , Proteína Disulfuro Isomerasas/metabolismo , Ingeniería de Proteínas/métodos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo
5.
Int J Med Microbiol ; 308(8): 977-985, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30131271

RESUMEN

Thioloxidoreductase HP0231 of Helicobacter pylori plays essential roles in gastric colonization and related gastric pathology. Comparative proteomics and analysis of complexes between HP0231 and its protein substrates suggested that several Hop proteins are its targets. HP0231 is a dimeric oxidoreductase that functions in an oxidizing Dsb (disulfide bonds) pathway of H. pylori. H. pylori HopQ possesses six cysteine residues, which generate three consecutive disulfide bridges. Comparison of the redox state of HopQ in wild-type cells to that in hp0231-mutated cells clearly indicated that HopQ is a substrate of HP0231. HopQ binds CEACAM1, 3, 5 and 6 (carcinoembryonic antigen-related cell adhesion molecules). This interaction enables T4SS-mediated translocation of CagA into host cells and induces host signaling. Site directed mutagenesis of HopQ (changing cysteine residues into serine) and analysis of the functioning of HopQ variants showed that HP0231 influences the delivery of CagA into host cells, in part through its impact on HopQ redox state. Introduction of a C382S mutation into HopQ significantly affects its reaction with CEACAM receptors, which disturbs T4SS functioning and CagA delivery. An additional effect of HP0231 on other adhesins and their redox state, resulting in their functional impairment, cannot be excluded.


Asunto(s)
Antígenos Bacterianos/metabolismo , Proteínas de la Membrana Bacteriana Externa/metabolismo , Proteínas Bacterianas/metabolismo , Traslocación Bacteriana , Infecciones por Helicobacter/microbiología , Helicobacter pylori/enzimología , Helicobacter pylori/patogenicidad , Oxidorreductasas/metabolismo , Antígenos Bacterianos/genética , Antígenos CD/genética , Antígenos CD/metabolismo , Adhesión Bacteriana , Proteínas de la Membrana Bacteriana Externa/genética , Proteínas Bacterianas/genética , Moléculas de Adhesión Celular/genética , Moléculas de Adhesión Celular/metabolismo , Línea Celular , Helicobacter pylori/genética , Humanos , Mutagénesis Sitio-Dirigida , Oxidorreductasas/genética , Transporte de Proteínas , Virulencia
6.
PLoS One ; 13(4): e0195358, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29677198

RESUMEN

Helicobacter pylori HP0377 is a thiol oxidoreductase, a member of the CcmG family involved in cytochrome biogenesis, as previously shown by in vitro experiments. In this report, we document that HP0377 also acts in vivo in the cytochrome assembly process in Bacillus subtilis, where it complements the lack of ResA. However, unlike other characterized proteins in this family, HP0377 is a dithiol reductase and isomerase. We elucidated how the amino acid composition of its active site modulates its functionality. We demonstrated that cis-proline (P156) is involved in its interaction with the redox partner (CcdA), as a P156T HP0377 variant is inactive in vivo and is present in the oxidized form in B. subtilis. Furthermore, we showed that engineering the HP0377 active motif by changing CSYC motif into CSYS or SSYC, clearly diminishes two activities (reduction and isomerization) of the protein. Whereas HP0377CSYA is inactive in reduction as well as in isomerization, HP0377CSYS retains reductive activity. Also, replacement of F95 by Q decreases its ability to regenerate scRNase and does not influence the reductive activity of HP0377CSYS towards apocytochrome c. HP0377 is also distinguished from other CcmGs as it forms a 2:1 complex with apocytochrome c. Phylogenetic analyses showed that, although HP0377 is capable of complementing ResA in Bacillus subtilis, its thioredoxin domain has a different origin, presumably common to DsbC.


Asunto(s)
Proteínas Bacterianas/metabolismo , Helicobacter pylori/enzimología , Oxidorreductasas/metabolismo , Secuencias de Aminoácidos , Secuencia de Aminoácidos , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Proteínas Bacterianas/genética , Clonación Molecular , Biología Computacional , Citocromos c/metabolismo , Escherichia coli , Helicobacter pylori/genética , Isoenzimas , Mutagénesis , Oxidación-Reducción , Oxidorreductasas/genética , Filogenia
7.
J Food Sci Technol ; 55(1): 408-417, 2018 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29358834

RESUMEN

Low-sugar gooseberry jams enriched by the addition of black chokeberry, elderberry, Japanese quince, flax seeds and wheat germs were examined for the content of total polyphenols, total flavonoids, and total anthocyanins as well as their antioxidant activity (DPPH, ABTS, and FRAP) and individual phenolic compounds. The jams were evaluated immediately after production and after 6 and 12 months of storage. Samples were stored at chilled temperature (10 °C) and room temperature (20 °C). A significant increase in the level of the analyzed components and antioxidant activity were determined in jams with the addition of chokeberry, elderberry and Japanese quince, while in the case of other plant ingredients the differences were not always significant. Immediately after production, the highest levels of total polyphenols (330 mg/100 g), total flavonoids (160 mg/100 g) and total anthocyanins (35 mg/100 g) were recorded in the gooseberry jam with a 15% addition of chokeberry fruit. In the examined jams, p-cumaric acid, ferulic acid, caffeic acid, (+)-catechin and rutin were identified and (+)-catechin were determined in the greatest quantities (1.874-5.660 mg/100 g). The storage conditions of jams determined the level of the examined constituents. Storage temperature generally had significant effect on the level of compounds with antioxidant properties, lower in the products which were chill-stored compared to those stored at room temperature. Anthocyanins were found to be the most sensitive components during storage.

8.
Appl Microbiol Biotechnol ; 101(10): 3977-3989, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28409380

RESUMEN

The recent, rapid increase in bacterial antimicrobial resistance has become a major public health concern. One approach to generate new classes of antibacterials is targeting virulence rather than the viability of bacteria. Proteins of the Dsb system, which play a key role in the virulence of many pathogenic microorganisms, represent potential new drug targets. The first part of the article presents current knowledge of how the Dsb system impacts function of various protein secretion systems that influence the virulence of many pathogenic bacteria. Next, the review describes methods used to study the structure, biochemistry, and microbiology of the Dsb proteins and shows how these experiments broaden our knowledge about their function. The lessons gained from basic research have led to a specific search for inhibitors blocking the Dsb networks.


Asunto(s)
Bacterias/enzimología , Disulfuros/química , Oxidorreductasas/metabolismo , Compuestos de Sulfhidrilo/metabolismo , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Bacterias/química , Bacterias/efectos de los fármacos , Bacterias/patogenicidad , Proteínas Bacterianas/química , Proteínas Bacterianas/efectos de los fármacos , Proteínas Bacterianas/metabolismo , Disulfuros/antagonistas & inhibidores , Virulencia/efectos de los fármacos
9.
Chembiochem ; 18(4): 402-412, 2017 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-28000364

RESUMEN

Galactosylceramidase (GALC) is the lysosomal ß-galactosidase responsible for the hydrolysis of galactosylceramide. Inherited deficiency in GALC causes Krabbe disease, a devastating neurological disorder characterized by accumulation of galactosylceramide and its deacylated counterpart, the toxic sphingoid base galactosylsphingosine (psychosine). We report the design and application of a fluorescently tagged activity-based probe (ABP) for the sensitive and specific labeling of active GALC molecules from various species. The probe consists of a ß-galactopyranose-configured cyclophellitol-epoxide core, conferring specificity for GALC, equipped with a BODIPY fluorophore at C6 that allows visualization of active enzyme in cells and tissues. Detection of residual GALC in patient fibroblasts holds great promise for laboratory diagnosis of Krabbe disease. We further describe a procedure for in situ imaging of active GALC in murine brain by intra-cerebroventricular infusion of the ABP. In conclusion, this GALC-specific ABP should find broad applications in diagnosis, drug development, and evaluation of therapy for Krabbe disease.


Asunto(s)
Galactosilceramidasa/genética , Galactosilceramidasa/metabolismo , Leucodistrofia de Células Globoides/enzimología , Sondas Moleculares , Enfermedades Carenciales/enzimología , Enfermedades Carenciales/genética , Galactosilceramidasa/antagonistas & inhibidores , Leucodistrofia de Células Globoides/diagnóstico , Leucodistrofia de Células Globoides/genética , Enfermedades por Almacenamiento Lisosomal/enzimología , Enfermedades por Almacenamiento Lisosomal/genética , Estructura Molecular , Mutación
10.
Eur J Med Chem ; 126: 160-170, 2017 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-27750150

RESUMEN

This report is about the identification, synthesis and initial biological characterization of derivatives of 4-epi-isofagomine as pharmacological chaperones (PC) for human lysosomal ß-galactosidase. The two epimers of 4-epi-isofagomine carrying a pentyl group at C-5a, namely (5aR)- and (5aS)-5a-C-pentyl-4-epi-isofagomine, were prepared by an innovative procedure involving in the key step the addition of nitrohexane to a keto-pentopyranoside. Both epimers were evaluated as inhibitors of the human ß-galactosidase: the (5aR)-stereoisomer (compound 1) was found to be a very potent inhibitor of the enzyme (IC50 = 8 nM, 30× more potent than 4-epi-isofagomine at pH 7.3) with a high selectivity for this glycosidase whereas the (5aS) epimer was a much weaker inhibitor. In addition, compound 1 showed a remarkable activity as a PC. It significantly enhanced the residual activity of mutant ß-galactosidase in 15 patient cell lines out of 23, with enhancement factors greater than 3.5 in 10 cell lines and activity restoration up to 91% of normal. Altogether, these results indicated that (5aR)-5a-C-pentyl-4-epi-isofagomine constitutes a promising PC-based drug candidate for the treatment of GM1-gangliosidosis and Morquio disease type B.


Asunto(s)
Inhibidores Enzimáticos/farmacología , Gangliosidosis GM1/genética , Iminopiranosas/farmacología , Lisosomas/enzimología , Mucopolisacaridosis IV/genética , Mutación , beta-Galactosidasa/antagonistas & inhibidores , Diseño de Fármacos , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Fibroblastos/efectos de los fármacos , Gangliosidosis GM1/enzimología , Gangliosidosis GM1/patología , Calor , Humanos , Concentración de Iones de Hidrógeno , Iminopiranosas/síntesis química , Iminopiranosas/química , Mucopolisacaridosis IV/enzimología , Mucopolisacaridosis IV/patología , Desnaturalización Proteica , beta-Galactosidasa/química , beta-Galactosidasa/genética , beta-Galactosidasa/metabolismo
11.
Front Microbiol ; 7: 1158, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27507968

RESUMEN

The formation of disulfide bonds that are catalyzed by proteins of the Dsb (disulfide bond) family is crucial for the correct folding of many extracytoplasmic proteins. Thus, this formation plays an essential, pivotal role in the assembly of many virulence factors. The Helicobacter pylori disulfide bond-forming system is uncomplicated compared to the best-characterized Escherichia coli Dsb pathways. It possesses only two extracytoplasmic Dsb proteins named HP0377 and HP0231. As previously shown, HP0377 is a reductase involved in the process of cytochrome c maturation. Additionally, it also possesses disulfide isomerase activity. HP0231 was the first periplasmic dimeric oxidoreductase involved in disulfide generation to be described. Although HP0231 function is critical for oxidative protein folding, its structure resembles that of dimeric EcDsbG, which does not confer this activity. However, the HP0231 catalytic motifs (CXXC and the so-called cis-Pro loop) are identical to that of monomeric EcDsbA. To understand the functioning of HP0231, we decided to study the relations between its sequence, structure and activity through an extensive analysis of various HP0231 point mutants, using in vivo and in vitro strategies. Our work shows the crucial role of the cis-Pro loop, as changing valine to threonine in this motif completely abolishes the protein function in vivo. Functioning of HP0231 is conditioned by the combination of CXXC and the cis-Pro loop, as replacing the HP0231 CXXC motif by the motif from EcDsbG or EcDsbC results in bifunctional protein, at least in E. coli. We also showed that the dimerization domain of HP0231 ensures contact with its substrates. Moreover, the activity of this oxidase is independent on the structure of the catalytic domain. Finally, we showed that HP0231 chaperone activity is independent of its redox function.

12.
ChemMedChem ; 9(12): 2647-52, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25377381

RESUMEN

Several families of iminosugar-based galactoside mimics were designed, synthesized, and evaluated as galactocerebrosidase (GALC) inhibitors. They were also tested as inhibitors of lysosomal ß- and α-galactosidases in order to find new potent and selective pharmacological chaperones for treatment of the lysosomal storage disorder, Krabbe disease. Whereas 1-C-alkyl imino-L-arabinitols are totally inactive toward the three enzymes, 1-C-alkyl imino-D-galactitols were found to be active only toward α-galactosidase A. Finally, 1-N-iminosugars provided the best results, as 4-epi-isofagomine was found to be a good inhibitor of both lysosomal ß-galactosidase and GALC. Further elaboration of this structure is required to achieve selectivity between these two galactosidases.


Asunto(s)
Galactósidos/química , Galactosilceramidasa/antagonistas & inhibidores , Iminoazúcares/química , alfa-Galactosidasa/antagonistas & inhibidores , beta-Galactosidasa/antagonistas & inhibidores , Galactosilceramidasa/metabolismo , Humanos , Iminopiranosas/antagonistas & inhibidores , Iminopiranosas/metabolismo , Iminoazúcares/metabolismo , Iminoazúcares/uso terapéutico , Leucodistrofia de Células Globoides/tratamiento farmacológico , Lisosomas/enzimología , Unión Proteica , Relación Estructura-Actividad , alfa-Galactosidasa/metabolismo , beta-Galactosidasa/metabolismo
13.
Carbohydr Res ; 380: 23-8, 2013 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-23896160

RESUMEN

Mono- and di-O-isopropylidene-l-sorbofuranose derivatives are important starting materials for the synthesis of modified sugars and useful chiral compounds. However, several inconsistencies in the spectral data of these compounds and erroneous structural assignments have been noted in the literature. The unambiguous synthesis of 1,2:4,6-di-O-isopropylidene-α-L-sorbofuranose and derivatives of 1,2- and 2,3-O-isopropylidene-α-L-sorbofuranoses has been achieved and definitive spectral data on these compounds are provided.


Asunto(s)
Carbohidratos/química , Carbohidratos/síntesis química , Sorbosa/análogos & derivados , Técnicas de Química Sintética , Sorbosa/síntesis química , Sorbosa/química , Análisis Espectral
14.
Pharmacol Rep ; 64(1): 123-8, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22580528

RESUMEN

There is a wide interpersonal difference to dobutamine response during dobutamine stress echocardiography (DSE). The aim of this study was to determine an association between GNB3 825C>T gene polymorphism, encoding the ß3-subunit of G protein, and heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP) response to dobutamine during DSE. The study involved 119 patients with clinical indications for DSE. Genotyping of GNB3 825C>T (rs5443) polymorphism was based on PCR-RFLP method with BseDI restriction enzyme. Significantly higher levels of both resting SBP and DBP in 825T allele carriers vs. 825CC patients were revealed. HR of 825CC vs. CT + TT subjects was slower along the test period reaching marked difference at dobutamine level 30 µg/kg/min (109 ± 20 vs. 116 ± 18 bpm, respectively, p = 0.047). SBP and DBP were markedly lower in 825CC homozygotes compared to 825T allele carriers throughout DSE. It can be concluded that GNB3 825C>T polymorphism is associated with resting SBP and DBP in Polish Caucasian patients subjected for diagnostic DSE. The polymorphism also modulate HR, SBP and DBP response during DSE.


Asunto(s)
Hemodinámica/genética , Proteínas de Unión al GTP Heterotriméricas/genética , Alelos , Presión Sanguínea/genética , Diástole/genética , Dobutamina , Ecocardiografía de Estrés/métodos , Ecoencefalografía/métodos , Femenino , Frecuencia Cardíaca/genética , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Sístole/genética
15.
Eur J Clin Pharmacol ; 67(5): 477-82, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21305273

RESUMEN

PURPOSE: The aim of this study was to determine an association between the ADRB1 1165C>G and 145A>G polymorphisms and hemodynamic response [heart rate (HR), systolic (SBP) and diastolic (DBP) blood pressure] to dobutamine during dobutamine stress echocardiography (DSE). METHODS: The study involved 144 patients with clinical indications for DSE. The PCR-restriction fragment length polymorphism method was used to identify the ADRB1 1165C>G and 145A>G polymorphisms. RESULTS: Heart rate during DSE increased in all analyzed study groups. Patients with the ADRB1 1165CC and 1165CG+GG polymorphisms demonstrated similar HR, including magnitude of response [change in heart rate (ΔHR 0-30): 42.1 ± 17.5 vs. 46.1 ± 15.5 bpm, respectively]. HR and ΔHR 0-30 were comparable in ADRB1145AA and 145AG subjects in the course of DSE. SBP and DBP at all stages of DSE were similar in subjects with either polymorphism and did not differentiate patients with the ADRB1 145AA polymorphism from those with the ADRB1 145AG polymorphism, nor those with the ADRB1 1165CC polymorphism from those with the ADRB1 1165CG+GG polymorphism. No differences were noted in the magnitude of response, with the increase in SBP and DBP comparable in all genotypes. Similar observations were made in patients (25/144 studied) with atropine requirements during DSE. CONCLUSION: The ADRB1 1165C>G and 145A>G polymorphisms are not associated with the HR, SBP and DBP responses in Polish Caucasian patients requiring diagnostic dobutamine stress echocardiography.


Asunto(s)
Ecocardiografía de Estrés , Hemodinámica/fisiología , Receptores Adrenérgicos beta 1/genética , Adulto , Anciano , Anciano de 80 o más Años , Presión Sanguínea/efectos de los fármacos , Cardiotónicos/farmacología , Diástole/efectos de los fármacos , Dobutamina , Femenino , Genotipo , Frecuencia Cardíaca/efectos de los fármacos , Hemodinámica/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo Genético , Sístole/efectos de los fármacos
16.
Pharmacogenomics J ; 10(2): 120-5, 2010 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-19752882

RESUMEN

New-onset, posttransplant diabetes mellitus (PTDM) has a high incidence after kidney transplantation in patients medicated with tacrolimus, and may adversely affect the patient and graft survival. The pathophysiology of PTDM closely mimics that of type II diabetes mellitus (T2DM). One of possible genetic factors predisposing to PTDM might be polymorphism in calpain-10 gene (CAPN10), previously associated with increased risk of T2DM in general population. Therefore, the present study was aimed at evaluation of CAPN10 gene polymorphisms in PTDM in kidney transplant patients medicated with tacrolimus. A total of 214 nondiabetic kidney transplant patients medicated with tacrolimus (56 patients with PTDM and 158 patients without PTDM were genotyped for the presence of CAPN10 gene variants (SNP-43: rs3792267:G>A, SNP-19: rs3842570 ins/del and SNP-63: rs5030952:C>T) using PCR-based assays. Frequency of SNP-63 minor allele was slightly increased in PTDM patients (P=0.056), and an association of SNP-63 heterozygosity and the risk of PTDM (odds ratios (OR)=2.45, P=0.023) was observed. An increased odds for PTDM development in patients carrying 1-1-2 haplotype (rs3792267:G-rs3842570:ins-rs5030952:T) compared to noncarriers was also noted (OR=2.35, P=0.026). Patients' higher body mass index and SNP-63 minor T allele carrier status were identified as independent PTDM risk factors, confirmed by multivariate regression analysis. This is the first study of CAPN10 polymorphism in relation to PTDM risk. However, the application of SNP-63 (rs5030952:C>T) as a marker of PTDM should be verified by further independent studies.


Asunto(s)
Calpaína/genética , Diabetes Mellitus Tipo 2/etiología , Trasplante de Riñón/efectos adversos , Adulto , Índice de Masa Corporal , Diabetes Mellitus Tipo 2/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Tacrolimus/uso terapéutico
17.
Psychiatr Pol ; 43(3): 329-40, 2009.
Artículo en Polaco | MEDLINE | ID: mdl-19725426

RESUMEN

AIM: Assessment of the cerebral blood perfusion among patients with eating (ED), anxiety (AD) and depressive disorders (DD), diagnosed according to ICD-10. METHOD: 57 females and 22 males, aged 17-50 were examined using the Single Photon Emission Computer Tomography (SPECT) and the neuropsychological tests, Benton and Bender. We also used the Beck Depression Inventory, the Hospital Anxiety and Depression Scale, and the Spielberger Self-Evaluation Questionnaire. Electroencephalography was also performed. RESULT: In ED, hypoperfusion occurred in 84.21%, and impairment of the central nervous system (CNS), was found in 27.77%, abnormalities in the electroencephalography--in 33.33% of the patients. In AD, hypoperfusion occurred in 72.72%, impairment of CNS--in 40%, abnormalities in EEG--in 48% of patients. In DD, hypoperfusion occurred in 81.48%, impairment of CNS--in 34.61%, abnormalities in EEG--in 38.46% of patients. CONCLUSIONS: Hypoperfusion was observed mostly among patients with ED, mainly in the frontal, temporal areas, and in the thalamus, on the left hand side, similar to DD group. Among patients with AD, hypoperfusion at the left hand side occurred almost three times more frequently than among patients with DD (Chi2 = 6.54, p < .025) and was significant. Anxiety as a trait was the highest in ED, but not significant. Among patients with AD, anxiety as a trait and as a state were almost at the same level.


Asunto(s)
Ansiedad/diagnóstico por imagen , Ansiedad/fisiopatología , Circulación Cerebrovascular , Trastorno Depresivo/diagnóstico por imagen , Trastorno Depresivo/fisiopatología , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico por imagen , Trastornos de Alimentación y de la Ingestión de Alimentos/fisiopatología , Adolescente , Adulto , Encéfalo/irrigación sanguínea , Encéfalo/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Perfusión , Cintigrafía , Flujo Sanguíneo Regional , Índice de Severidad de la Enfermedad , Adulto Joven
18.
Psychiatr Pol ; 39(4): 701-8, 2005.
Artículo en Polaco | MEDLINE | ID: mdl-16237975

RESUMEN

The long and difficult diagnostic and therapeutic process in a 21 year old patient with hypochondriac disorder was presented. In the past he had the streptococcal throat infection and during 5 years he was diagnosed and treated because of headache, heart, muscles and joints pains. His blood pressure was occasionally high. He had tonsillectomy and his ASO index was high (from 405 IU/ml to 2500 IU/ml). His cranial CT, EEG, ECG were normal. Finally he was diagnosed as having hypochondriac disorder and began psychiatric treatment. Because of lacking improvement in the out-patient therapy he was admitted to the Neurotic Ward of Medical Academy in Gdansk. The results of cerebral SPECT showed hypoperfusion in different regions (prefrontal, frontal, temporal, parietal, about medial from 5-22%). The antibodies ABA type II/20/, ACA/ CA/ type III /10/, MSA /ASMA/++/ were found. The level of thrombomodulin was 36.64 ng/ ml. Psychological tests (Benton, Bender, MMPI) were normal. In result of the above findings and observation the diagnosis was changed from hypochondriac disorder to secondary immunologic vasculitis. The patient received probably the possibility to be properly treated.


Asunto(s)
Errores Diagnósticos , Hipocondriasis/diagnóstico , Dolor/etiología , Infecciones Estreptocócicas/inmunología , Vasculitis/diagnóstico , Vasculitis/inmunología , Adulto , Artralgia/etiología , Cefalea/etiología , Corazón/fisiopatología , Humanos , Masculino , Músculo Esquelético/fisiopatología , Infecciones Estreptocócicas/complicaciones , Factores de Tiempo , Tomografía Computarizada de Emisión de Fotón Único , Vasculitis/complicaciones
19.
Psychiatr Pol ; 39(3): 497-507, 2005.
Artículo en Polaco | MEDLINE | ID: mdl-16149759

RESUMEN

AIM: The aim of the study was to estimate usefulness of the single photon emission computed tomography (SPECT) for the diagnostics of the depressive disorders, neurotic and eating disorders, and detect the organic factors and correlation between cerebral hypoperfusion and results of Benton's and Bender's tests. MATERIAL AND METHOD: Study of 43 patients (33 women and 10 men) aged 16--59 years (SD+38, 65 +/- 11, 62) which were examined with single photon emission computed tomography (SPECT) and Benton's and Bender's tests during their treatment in the 1st Department of Psychiatry, Medical University in Gdansk in the years 2000 to 2003. 30 patients were diagnosed with depression (first depressive episodes--8, recurrent depressive disorders--9, organic depression--13), 8--neurotic disorders and 5--eating disorders. RESULTS AND CONCLUSIONS: SPECT in 38 (88,37%) cases showed hypoperfusion mostly on the left side and in the frontal region. Hypoperfusion in the recurrent depressive disorders was considerably greater (nearly significant) in comparison with the first depressive episodes. The correlation between hypoperfusion and CNS impairment examined with Benton's and Bender's tests was observed. The correlation coefficient of was 0.6845.


Asunto(s)
Trastorno Depresivo/diagnóstico por imagen , Trastornos de Alimentación y de la Ingestión de Alimentos/diagnóstico por imagen , Trastornos Neuróticos/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Adolescente , Adulto , Encéfalo/irrigación sanguínea , Encéfalo/fisiopatología , Trastorno Depresivo/fisiopatología , Trastornos de Alimentación y de la Ingestión de Alimentos/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos Neuróticos/fisiopatología , Proyectos Piloto , Flujo Sanguíneo Regional , Sensibilidad y Especificidad , Exametazima de Tecnecio Tc 99m
20.
Psychiatr Pol ; 37(5): 851-6, 2003.
Artículo en Polaco | MEDLINE | ID: mdl-14631605

RESUMEN

A case of severe organic affective disorder after head trauma with loss of consciousness is presented. While CT in this case was normal, SPECT brain perfusion imaging showed hipoperfusion in the right frontal lobe and the left temporal-parietal region. The psychologic tests: Benton, Bender, MMPI confirmed changes in CNS as well. These findings help to explain the severity and chronicity of disorders and medical certification.


Asunto(s)
Encéfalo/irrigación sanguínea , Traumatismos Craneocerebrales/psicología , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/etiología , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Femenino , Hemodinámica/fisiología , Humanos
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