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1.
Int Orthop ; 45(4): 857-863, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-32940751

RESUMO

PURPOSE: The aim of the study was to assess whether administration of a single dose of methylprednisolone in the group patients above 65 years of age will be effective in complex analgesic management after total hip arthroplasty (THA). METHODS: Seventy-seven patients above 65 years old were double-blind randomized into two: the study and controls groups. Pre-operatively, the study group received as a single dose of 125 mg intravenous methylprednisolone, while the others saline solution as placebo. Peri-operatively, all the patients were administered opioid and nonopioid analgesic agents. We measured the levels of inflammatory markers (leukocytosis, C-reactive protein-CRP), pain intensity level (visual analog scale-VAS; numerical rating scale-NRS), the life parameters, and noted complications. RESULTS: Following administration of methylprednisolone were significantly lower levels of CRP on all the four post-operative days; leukocytosis on the second day; the VAS/NRS score at rest after six, 12, and 18 hours post-operatively, diminished the dose of parenteral opioid preparations (oxycodone hydrochloride), the duration of analgesia by peripheral nerve block was significantly higher as compared with the placebo group (p < 0.000001). No infectious complications were noted; there was one patient who developed post-operative delirium. CONCLUSION: A single dose of methylprednisolone significantly reduces the level of post-operative pain at rest on the day of THA in the group patients above 65 years of age, decreases the dose of opioid analgesic agents, and significantly decreases the level of inflammatory markers, without infectious processes.


Assuntos
Artroplastia de Quadril , Idoso , Analgésicos Opioides , Artroplastia de Quadril/efeitos adversos , Convalescença , Método Duplo-Cego , Humanos , Metilprednisolona , Manejo da Dor , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/tratamento farmacológico
2.
Haematologica ; 103(11): 1843-1852, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30002127

RESUMO

A cute myeloid leukemia is a malignant disease of immature myeloid cells. Despite significant therapeutic effects of differentiation-inducing agents in some acute myeloid leukemia subtypes, the disease remains incurable in a large fraction of patients. Here we show that SK053, a thioredoxin inhibitor, induces differentiation and cell death of acute myeloid leukemia cells. Considering that thioredoxin knock-down with short hairpin RNA failed to exert antiproliferative effects in one of the acute myeloid leukemia cell lines, we used a biotin affinity probe-labeling approach to identify potential molecular targets for the effects of SK053. Mass spectrometry of proteins precipitated from acute myeloid leukemia cells incubated with biotinylated SK053 used as a bait revealed protein disulfide isomerase as a potential binding partner for the compound. Biochemical, enzymatic and functional assays using fluorescence lifetime imaging confirmed that SK053 binds to and inhibits the activity of protein disulfide isomerase. Protein disulfide isomerase knockdown with short hairpin RNA was associated with inhibition of cell growth, increased CCAAT enhancer-binding protein α levels, and induction of differentiation of HL-60 cells. Molecular dynamics simulation followed by the covalent docking indicated that SK053 binds to the fourth thioredoxin-like domain of protein disulfide isomerase. Differentiation of myeloid precursor cells requires the activity of CCAAT enhancer-binding protein α, the function of which is impaired in acute myeloid leukemia cells through various mechanisms, including translational block by protein disulfide isomerase. SK053 increased the levels of CCAAT enhancer-binding protein α and upregulated mRNA levels for differentiation-associated genes. Finally, SK053 decreased the survival of blasts and increased the percentage of cells expressing the maturation-associated CD11b marker in primary cells isolated from bone marrow or peripheral blood of patients with acute myeloid leukemia. Collectively, these results provide a proof-of-concept that protein disulfide isomerase inhibition has potential as a therapeutic strategy for the treatment of acute myeloid leukemia and for the development of small-molecule inhibitors of protein disulfide isomerase.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Dipeptídeos/farmacologia , Inibidores Enzimáticos/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Metacrilatos/farmacologia , Proteínas de Neoplasias/antagonistas & inibidores , Isomerases de Dissulfetos de Proteínas/antagonistas & inibidores , Feminino , Células HL-60 , Humanos , Leucemia Mieloide Aguda/enzimologia , Leucemia Mieloide Aguda/patologia , Masculino , Proteínas de Neoplasias/metabolismo , Isomerases de Dissulfetos de Proteínas/metabolismo
3.
Br J Haematol ; 174(4): 582-90, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27097566

RESUMO

Mounting evidence suggests that autoreactivity and inflammatory processes are involved in the pathogenesis of chronic lymphocytic leukaemia (CLL). Cytoskeletal proteins, including non-muscle myosin heavy chain IIA (MYHIIA), vimentin (VIM) and cofilin-1 (CFL1), exposed on the surface of apoptotic cells have been identified as autoantigens that are recognized by the specific B-cell receptors of the CLL cells. In 212 CLL patients analysed with quantitative reverse transcriptase-polymerase chain reaction we found CFL1 overexpression and low expression of MYH9 in comparison with healthy volunteers. We detected specific cytotoxic immune responses for peptides derived from MYHIIA in 66·7%, VIM in 87·5% and CFL1 in 62·5% CLL patients in an Enzyme-Linked ImmunoSpot assay. Low frequencies of autoreactive peptide-specific T cells were detected against MYHIIA, VIM and CFL1 in CLL patients ex vivo; most of the detected cells had an effector-memory phenotype. Our findings support the existence of cytotoxic immune responses against three autoantigens that have been identified as targets of CLL clonotypic B-cell receptors. The presence of autoreactive CD8(+) T cells against MYHIIA, VIM and CFL1 in CLL patients indicates the involvement of antigen-specific autoreactive T cells in the pathogenesis of CLL.


Assuntos
Autoantígenos/imunologia , Leucemia Linfocítica Crônica de Células B/imunologia , Linfócitos T Citotóxicos/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Cofilina 1/imunologia , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Masculino , Pessoa de Meia-Idade , Cadeias Pesadas de Miosina/imunologia , Vimentina/imunologia
4.
Acta Haematol ; 134(4): 255-62, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26159545

RESUMO

BACKGROUND: The programmed death 1 (PD-1) receptor pathway is responsible for the negative regulation of both T and B lymphocytes upon activation of these cells. There is growing evidence that chronic lymphocytic leukemia (CLL) cells exploit the PD-1 ligand (PD-L1) to resist antitumor immune reactions and maintain their survival by shaping their own microenvironment. METHODS: We used a quantitative RT-PCR method to analyze PD-L1 gene expression in bone marrow and peripheral blood mononuclear cells, representing the proliferation and accumulation compartments of CLL. RESULTS: PD-L1 expression was found to be significantly higher in 112 CLL patients than in controls. Levels of PD-L1 expression in bone marrow and peripheral blood were comparable and showed a positive correlation. Furthermore, expression of PDL1 strongly correlated with expression of PD-1 receptor in mononuclear cells from the same compartment, and was not affected by incubation with immunomodulatory drug thalidomide. CONCLUSION: PD-L1 expression is shared between CLL cells localized in distinct disease compartments, demonstrating that PD-1/PD-L1 a universal target for therapy.


Assuntos
Antígeno B7-H1/biossíntese , Células da Medula Óssea/metabolismo , Regulação Leucêmica da Expressão Gênica , Leucemia Linfocítica Crônica de Células B/sangue , Leucócitos Mononucleares/metabolismo , Proteínas de Neoplasias/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Células da Medula Óssea/patologia , Feminino , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Linfocítica Crônica de Células B/terapia , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/biossíntese
6.
Przegl Lek ; 69(1): 19-24, 2012.
Artigo em Polonês | MEDLINE | ID: mdl-22764514

RESUMO

PURPOSE OF THE STUDY: To assess the effectiveness of postoperatively applied pharmacological prophylaxis and the impact of demographic parameters (age, height, weight), gestational age, parturients' morbidity (hypertension, motion sickness), postoperative fluid resuscitation, applied anaesthetic technique (spinal needle type and diameter, patient's positioning, choice of intervertebral space for puncturing dura, a dose of local anaesthetic) on the incidence of PDPH after spinal anaesthesia for Caesarean section. MATERIAL AND METHODS: There were analyzed 182 mothers who delivered by Caesarean section under spinal anaesthesia. Postoperative management included fluid administration 2500 ml daily and i.v. antibiotic prophylaxis (control group, n = 560). The consecutive groups of patients were administered antibiotic and fluids in dose as mentioned above, and additionally oral caffeine 3 x 200 mg (n = 40); caffeine plus magnesium 2 x 1 g daily i.v. (n = 42) or caffeine plus magnesium plus aminophylline 250 mg i.v. once daily (n = 40). Incidence of PDPH was analyzed in all the groups of patients. RESULTS: The incidence of PDPH was lower after usage of thin spinal needles (Spinokan 27G), but statistical significance was p = 0.07. The other analyzed factors did not affect the incidence of PDPH. None of the applied pharmacoprophylactic methods appeared to be efficacious. The volume of administered within 18 hours postoperatively crystalloids was larger in the group of patients with multifactorial pharmacoprophylaxis (p = 0.04), probably due vasodilatation caused by synergistic effect of magnesium and aminophylline; explanation of this phenomenon is arguable, however. CONCLUSIONS: Neither prophylactic administration of caffeine, magnesium or aminophylline, nor postoperative fluid administration, did not influence the incidence of PDPH.


Assuntos
Anestesia Obstétrica/efeitos adversos , Raquianestesia/efeitos adversos , Cesárea/efeitos adversos , Cefaleia Pós-Punção Dural/epidemiologia , Cefaleia Pós-Punção Dural/prevenção & controle , Adolescente , Adulto , Aminofilina/administração & dosagem , Antibioticoprofilaxia , Cafeína/administração & dosagem , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Incidência , Magnésio/administração & dosagem , Cefaleia Pós-Punção Dural/etiologia , Cuidados Pós-Operatórios , Gravidez , Adulto Jovem
7.
Przegl Lek ; 69(5): 184-93, 2012.
Artigo em Polonês | MEDLINE | ID: mdl-23050414

RESUMO

PURPOSE OF THE STUDY: To compare predicted death rate (PDR) numbers, computed in commonly used severity-of-illness and prognostic scoring systems (Portsmouth-POSSUM, SAPS 2, MPM 2, MPM for cancer patients, LODS, ODIN i TRIOS) on the first and on the third postoperative days with the mean PDR calculated from the scales. Assessment of the mean PDR values. Analysis of the main risk factors that affect postoperative mortality. MATERIAL AND METHODS: There were analyzed 187 cases of non-survivors and 100 cases of survivors treated in surgical wards at University Hospital in Kraków. In each case there were compared groups of patients with defined pathological syndromes (sepsis, thromboembolism, left-heart failure, respiratory tract infections, trauma, oncology, multiorgan failure and haemorrhage) with PDR calculated in seven severity-of illness and prognostic scoring systems on the first and on the third postoperative day and mean PDR computed from seven PDR numbers. There was used calculation of OR (odds ratio) with 95% CI (confidence interval) and the Pearson product moment correlation coefficient. RESULTS: The main risk factors of early deaths (that occurred within the first 3 postoperative days) in the group of nonsurvivors (n = 187) were: emergencies (p < 0.001), perioperative haemorrhage (p < 0.002), and trauma (p = 0.02). The late deaths (that occurred > 3 postoperative days) were caused by repeated surgery (p < 0.001), oncology (p = 0.019), then comorbidities (p = 0.025) and sepsis (p = 0.072). The Pearson product moment correlation coefficients for mean PDR computed on the 1st and 3rd postoperative day were respectively -0.4517 and -0.4012. None of the scales showed good discriminant characteristics in patients with cardiovascular diseases and pneumonia. In all scoring systems, except of the MPM for cancer patients and TRIOS, the PDR values correlated significantly with the preoperative ASA group assessment. CONCLUSIONS: There is no commonly used severity-of-illness scoring system that could properly evaluate intensive care unit patients. Discriminative abilities of the scoring systems do not present any unique features that might affect selection of one of them. The mean PDR value computed from available scales is a reasonable descriptive and prognostic alternative.


Assuntos
Causas de Morte , Inquéritos Epidemiológicos/estatística & dados numéricos , Hospitais Universitários/estatística & dados numéricos , Índice de Gravidade de Doença , Procedimentos Cirúrgicos Operatórios/mortalidade , Humanos , Polônia/epidemiologia , Prognóstico , Fatores de Risco , Taxa de Sobrevida
8.
Przegl Lek ; 69(4): 129-36, 2012.
Artigo em Polonês | MEDLINE | ID: mdl-23029705

RESUMO

PURPOSE OF THE STUDY: To compare and evaluate preoperative assessment in ASA scale to predicted death rate (PDR) numbers, computed in commonly used severity-of-illness and prognostic scoring systems (Portsmouth-POSSUM, SAPS 2, MPM 2, MPM for cancer patients, LODS, ODIN i TRIOS) on the first and on the third postoperative days. Evaluation of the mean PDR calculated from the scales. MATERIAL AND METHODS: There were analyzed 187 cases of non-survivors and 100 cases of survivors of 187 patients treated in surgical intensive care unit at University Hospital in Kraków. In each case PDR was calculated in seven severity-of illness and prognostic scoring systems on the first and on the third postoperative day and compared to the ASA group and mean PDR computed from seven PDR numbers. Discrimination and calibration characteristics of the scoring systems was analyzed as area under receiver operating characteristic curves (AUROC) and predictive values. RESULTS: Length of hospital stay was shorter in survivors (16.6 days) as compared to nonsurvivors (25.3 days); similarly the time period between the hospital admittance and surgery was shorter in survivors (1.6 days vs 7.4 days). There were almost twice more frequent repeated surgical procedures in nonsurvivors (45.4% vs 26%). The mean ASA scale in non-survivors was 3.74 and 3.20 in survivors (p < 0.001). The mean PDR computed from seven scoring systems on the first postoperative day was 55.2 in non-survivors vs 21.2 in survivors (p < 0.001) and on the third postoperative day was 64.1 vs 32.3 (p < 0.001). The best discriminative properties, calculated as AUROC, showed: mean PDR computed from the used scoring systems on the first postoperative day (0.859), then ODIN (0.847), MPM2 (0.833), Portsmouth-POSSUM (0.83) and mean PDR computed on the third postoperative day (0827). CONCLUSIONS: There is none severity-of-illness nor prognostic scoring system that could be commonly used in intensive care unit patients. There are discrepancies in predicted death rate (PDR) cal. culated in each of available risk models in population of intensive care unit patients. The mean PDR value computed from available scales could be a reasonable descriptive and prognostic alternative.


Assuntos
Cuidados Críticos/métodos , Cuidados Críticos/estatística & dados numéricos , Complicações Pós-Operatórias/classificação , Complicações Pós-Operatórias/mortalidade , Índice de Gravidade de Doença , Sobreviventes/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Polônia , Período Pós-Operatório , Prognóstico , Curva ROC , Análise de Sobrevida , Adulto Jovem
9.
Sci Rep ; 12(1): 2320, 2022 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-35149701

RESUMO

The aim of this study is to assess whether administration of gabapentin and methylprednisolone as "pre-emptive analgesia" in a group of patients above 65 years of age would be effective in complex pain management therapy following total knee arthroplasty (TKA). One hundred seventy patients above 65 years were qualified for the study, with exclusion of 10 patients due to clinical circumstances. One hundred sixty patients were randomly double-blinded into two groups: the study group (80 patients) and the control group (80 patients). The study group received as "pre-emptive" analgesia a single dose of 300 mg oral (PO) gabapentin and 125 mg intravenous (IV) methylprednisolone, while the control received a placebo. All patients received opioid and non-opioid analgesic agents perioperatively calculated for 1 kg of total body weight. We measured (1) pain intensity level at rest (numerical rating scale, NRS), (2) life parameters, (3) levels of inflammatory markers (leukocytosis, C reactive protein CRP), and (4) all complications. Following administration of gabapentin and methylprednisolone as "pre-emptive" analgesia, the NRS score at rest was calculated at 6, 12 (p < 0.000001), 18 (p < 0.00004) and 24 (p = 0.005569) h postoperatively. Methylprednisolone with gabapentin significantly decreased the dose of parenteral opioid preparations (p = 0.000006). The duration time of analgesia was significantly longer in study group (p < 0.000001), with CRP values lower on all postoperative days (1, 2 days-p < 0.00001, 3 days-p = 0.00538), and leukocytosis on day 2 (p < 0.0086) and 3 (p < 0.00042). No infectious complications were observed in the first postoperative days; in the control group, one patient manifested transient ischemic attack (TIA). The use of gabapentin and methylprednisolone as a single dose decreased the level of postoperative pain on the day of surgery, the dose of opioid analgesic preparations, and the level of inflammatory parameters without infectious processes.


Assuntos
Analgésicos/uso terapêutico , Artroplastia do Joelho , Gabapentina/uso terapêutico , Metilprednisolona/uso terapêutico , Manejo da Dor , Dor Pós-Operatória/prevenção & controle , Pré-Medicação , Analgésicos/efeitos adversos , Analgésicos Opioides/efeitos adversos , Analgésicos Opioides/uso terapêutico , Método Duplo-Cego , Gabapentina/administração & dosagem , Gabapentina/efeitos adversos , Humanos
10.
PLoS One ; 17(10): e0276674, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36282861

RESUMO

OBJECTIVES: Chronic lymphocytic leukemia (CLL) is a lymphoproliferative disease with heterogeneous clinical course. Recent studies revealed a link between NOTCH1 mutation and the overexpression of MYC and MYC-related genes involved in ribosome biogenesis and protein biosynthesis, such as nucleophosmin-1 (NPM1), in CLL cells. In the present study, we aim to evaluate the impact of the NOTCH1 mutation on the MYC and MYC induced NPM1 expression in CLL cells via quantification of their transcripts. METHODS: Using qRT-PCR, we analyzed the levels of MYC and three main NPM1 splice variants in 214 samples collected from CLL patients. We assessed the impact of each splice variant on CLL prognostic markers, including the IGHV, TP53, NOTCH1, SF3B1, and MYD88 mutational status, cytogenetic aberrations, and laboratory features. RESULTS: Significantly higher levels of NPM1.R1 transcripts in patients with unmutated compared to mutated IGHV status were found. The median time to first treatment (TTFT) in patients with a high level of NPM1.R1 was significantly shorter compared to the group with low NPM1.R1 levels (1.5 vs 33 months, p = 0.0002). Moreover, in Multivariate Cox Proportional Hazard Regression Model NPM1.R1 splice variant provided an independent prognostic value for TTFT. CONCLUSION: In conclusion, our study indicates the prognostic significance of the level of NPM1.R1 expression and suggests the importance of splicing alterations in the pathogenesis of CLL.


Assuntos
Leucemia Linfocítica Crônica de Células B , Humanos , Leucemia Linfocítica Crônica de Células B/patologia , Fator 88 de Diferenciação Mieloide/genética , Processamento Alternativo , Mutação , Prognóstico , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo
12.
Postepy Hig Med Dosw (Online) ; 65: 764-9, 2011 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-22173441

RESUMO

INTRODUCTION: The aim of the study was to determine the potential relation between vegetarian diet and tooth erosion and abrasion. MATERIAL/METHODS: The examination included 46 vegetarians and the same number in the control group. Clinical research was carried out in order to detect the presence of abrasive and erosive changes and the level of hygiene in oral cavities. The questionnaire survey concerned dietary and hygienic habits. Statistical analysis of the data was conducted with Chi-square test and Mann-Whitney U test. The relations between following a vegetarian diet and the occurrence of non-carious cavities was tested with models of logistic regression. RESULTS: Tooth erosion was present among 39.1% of vegetarians and 23.9% of controls, while abrasion appeared among 26.1% and 10.9%, respectively, and the differences were statistically insignificant. The distribution of the changes was similar in both groups. Among vegetarians, significantly more frequent consumption of sour products (predominantly raw vegetables and fruit and tomatoes) was observed. The level of oral hygiene and hygienic habits were similar in both groups. The analysis of statistical regression did not reveal any relations between following a vegetarian diet and the occurrence of tooth erosion and abrasion. DISCUSSION: The results did not reveal any direct influence of vegetarian diet on the occurrence of erosive and abrasive changes. However, in the vegetarian group, more frequent consumption of some sour products and more commonly used horizontal brushing method were observed, with a slightly higher occurrence of non-carious cavities. Further research is required to obtain unambiguous conclusions.


Assuntos
Cárie Dentária/etiologia , Dieta Vegetariana/efeitos adversos , Higiene Bucal/métodos , Abrasão Dentária/etiologia , Erosão Dentária/etiologia , Adolescente , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Concentração de Íons de Hidrogênio , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Adulto Jovem
13.
Przegl Lek ; 68(5): 274-9, 2011.
Artigo em Polonês | MEDLINE | ID: mdl-21961416

RESUMO

Haemorrhage into the digestive tract lumen in elderly patients leads directly to multiorgan instability and failure. Analysis of 68 ICU patients, treated in 2007-2008 proved interdependence between presenting co-existing diseases, including reduction of vital organ reserve, and multiorgan dysfunction. Each patient was evaluated consecutively according to four commonly accepted severity-of-illness scoring systems (severity models): SAPS2, LODS, MODS and POSSUM. The assessment was displayed in numbers (predicted death rate, PDR) and in binary system of survivors (60%) and non-survivors (40%). The last group was divided into two subgroups: a/. those, who survived (their average PDR calculated in SAPS 2 on admittance was 22.3 vs after surgery on ICU was 25.1, and respectively computed in LODS on admittance was 17.4 vs after surgery on ICU was 21.4), and b/. those, who died shortly after hospital admittance, or following surgery in the ICU (their average PDR calculated on admittance in SAPS2 was 34.8 vs after surgery on ICU was 62.3, and respectively computed in LODS on admittance was 30.0 vs after surgery on ICU was 57.2). In POSSUM average PDR calculated for survivors was 61.6 vs for 85.4 in non-survivors. The difference was also noticed during collecting points in severity scoring systems: in MODS for non-survivors (3.3 on admittance vs 7.5 calculated in ICU after surgery), and in LODS (5.8 vs 9.5, respectively), p<0.001. The main risk factors were systolic blood pressure < 90 mmHg, HR > 140/min, Glasgow Coma Scale < 12, urine output < 20ml/ h, Hb < 8.5 g/L, creatinine > 350 micromol/l, paO2 < 60 mmHg, INR > 2,2, catecholamine i.v. administration > 1 h, mechanical ventilation > 48h, surgery < 2h following patients hospital admittance. In non-survivor group there were more than two co-existing diseases in the 3rd or 4th degree of advancement (p<0.004).


Assuntos
Unidades de Terapia Intensiva/estatística & dados numéricos , Choque Hemorrágico/mortalidade , Choque Hemorrágico/terapia , Distribuição por Idade , Idoso , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação , Masculino , Polônia/epidemiologia , Fatores de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Taxa de Sobrevida
14.
Przegl Lek ; 68(6): 296-302, 2011.
Artigo em Polonês | MEDLINE | ID: mdl-22039665

RESUMO

Digestive tract acute haemorrhage has been recognized as one of the major risk factors in mortality of surgical patients. A group of 68 elderly ICU patients with non-traumatic haemorrhagic shock (aged 65-95 yrs) was observed. The patients were evaluated according to commonly used severity-of-illness scoring systems: SAPS2, LODS and POSSUM. A retrospective analysis was based on two groups: a) survivors, and b) nonsurvivors. In both groups there was calculated predicted death rate (PDR): on hospital admittance (in SAPS 2 22.3 in survivors vs 34.8 in non-survivors, in LODS 17.4 vs 30.6, respectively), 2 hrs after surgery (in SAPS 2 25.1 in survivors vs 62.3 in non-survivors, in LODS 21.4 vs 57.2, and in POSSUM 61,6 vs 85.4, respectively), and after the first day of ICU treatment (in SAPS 2 35.0 in survivors vs 70.2 in non-survivors, in LODS 32.5 vs 58.2 respectively); p<001. Similarly, numbers of collected points in Therapeutic Intervention Scoring system (TISS-28) were statistically significant between the groups: 36.1 in survivors vs 47.1 in non-survivors, and in TISS-76: 34.0 vs 45.1, respectively p<0.001. The difference was also noticed during collecting points in severity scoring systems: MODS and SOFA; a number of collected points was twice higher when measured after the surgery, than when comparing the MODS and SOFA values, calculated on hospital admittance in non-survivor group.


Assuntos
Hemorragia Gastrointestinal/mortalidade , Unidades de Terapia Intensiva/estatística & dados numéricos , Complicações Pós-Operatórias/mortalidade , Índice de Gravidade de Doença , Choque Hemorrágico/classificação , Choque Hemorrágico/mortalidade , Idoso , Idoso de 80 Anos ou mais , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação , Masculino , Insuficiência de Múltiplos Órgãos , Estudos Retrospectivos , Análise de Sobrevida
15.
Anticancer Res ; 40(11): 6327-6335, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109570

RESUMO

BACKGROUND/AIM: Despite numerous studies, the etiology of chronic lymphocytic leukemia (CLL) remains unknown. A hypothesis of autoantigen stimulation in leukemic clone selection might explain 'stereotypy' of B-cell receptors. In healthy cells, cofilin-1 (CFL1) has multiple functions. Its role was described in several malignancies. The aim of this study was characterization of the role of CFL1 in CLL. Materialas and Methods: Cells from peripheral blood of 180 patients and 42 healthy volunteers (HVs) were isolated. Gene expression was assessed with reverse transcription polymerase chain reaction (RT-qPCR); western blot was performed for determination of protein level and activity. After silencing of CFL1 gene, cell ability for migration and chemotaxis was investigated with Transwell method. Post-silencing, apoptosis and cell cycle was determined by flow cytometry. RESULTS: In RT-qPCR, we observed significantly higher expression of CFL1. Higher activity of protein in CLL cells when compared to HVs was detected. Knock-down of CFL1 led to decreased chemotaxis and migration of CLL cells versus cells from HVs. Apoptosis was increased amongst cells with silenced CFL1 and correlated with higher proportion of cells in the G2/M phase. CONCLUSION: Significantly higher expression of CFL1 mRNA in CLL and higher protein activity might indicate high utilization of CFL1 in malignant cells, maintaining their viability, as its inhibition affected viability, cell-cycle progression and motility of leukemia cells.


Assuntos
Cofilina 1/metabolismo , Leucemia Linfocítica Crônica de Células B/metabolismo , Leucemia Linfocítica Crônica de Células B/patologia , Transdução de Sinais , Adulto , Idoso , Idoso de 80 Anos ou mais , Apoptose/genética , Linhagem Celular Tumoral , Sobrevivência Celular , Quimiotaxia/genética , Cofilina 1/genética , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Frações Subcelulares/metabolismo
16.
Adv Clin Exp Med ; 26(7): 1147-1153, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29211365

RESUMO

Cystic fibrosis is a genetic disorder in which the mutation of the Cystis Fibrosis Transmembrane Conductance Regulator (CFTR) gene that codes the protein forming a chloride channel of epithelial cells results in its distorted functioning. The manifestations of the disorder are mainly observed in the respiratory and digestive system. Accumulation of sticky and thick mucus is the dominant clinical symptom; it leads to chronic infections and gradual tissue destruction. Although cystic fibrosis remains incurable, it is currently feasible to extend patients' life expectancy thanks to modern therapy possibilities. As cystic fibrosis is no longer the domain of pediatricians, health care to CF patients needs to be provided by doctors of various specializations. The multidisciplinary team of doctors should include a dentist aware of specific prevention and treatment needs of this group of patients. It results from the fact that in the course of cystic fibrosis it is possible to observe a variety of changes in the oral cavity environment. The study presents dental issues observed in CF patients and reported in literature. Particular attention was paid to dental caries, mineralization disorders of hard dental tissues, gingivitis and the change in the content and properties of saliva; moreover, prevention and treatment options regarding oral cavity health is this group of patients were taken into consideration.


Assuntos
Fibrose Cística/complicações , Saúde Bucal , Calcificação Fisiológica , Cárie Dentária/prevenção & controle , Gengivite/prevenção & controle , Humanos
17.
Oncotarget ; 8(56): 95163-95175, 2017 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-29221119

RESUMO

Mutations of the nucleophosmin-1 (NPM1) gene in cytogenetically normal (CN) acute myeloid leukemia (AML) identify a group of patients with more favorable prognosis. NPM1 encodes three main alternatively spliced isoforms R1(B23.1), R2(B23.2), and R3(B23.3). The expression of splice variants R1, R2 and R3 were higher in AML patients compared to normal cells of healthy volunteers (HVs), although RNA-seq analysis revealed enhanced R2 expression also in less differentiated cells of HVs as well as in AML cells. The variant R2, which lacks exons 11 and 12 coding for the nucleolar localization domain, might behave similar to the mutant form of NPM1 (NPM1mut). In accordance, in CN-AML high R2 expression was associated with favorable impact on outcome. Moreover, functional studies showed nucleolar localization of the eGFP-NPM1 wildtype and cytoplasmic localization of the eGFP-NPM1 mut protein. While the eGFP-NPM1 R2 splice variant localized predominantly in the nucleoplasm, we also could detect cytoplasmic expression for the R2 variant. These results support a unique biological consequence of R2 overexpression and in part explain our clinical observation, where that high R2 variant expression was associated with a better prognosis in CN-AML patients.

18.
J Trace Elem Med Biol ; 41: 107-110, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28347456

RESUMO

The intensity of the cariostatic activity of fluoride ions can be attributed to their multidirectional influence on the caries process. They are an irreplaceable factor that helps sustain mineral balance of dental tissues, simultaneously demonstrating antibacterial properties. As a consequence, many manufacturers of fissure sealants include fluoride ions in their products. The aim of this in vitro study was to determine long-term fluoride release from four fissure sealants (Conseal F, Fissurit FX, Delton Fs+, Admira Seal). During a 14-week-long observation, all the materials showed a relatively constant level of F- release; however, it is crucial to mention that within the first 48h, the most significant increase in fluoride release was found for Fissurit and Delton sealants. Based on the overall assessment, the highest total amount of the released fluoride ions was observed for Delton, and the lowest level was reported for Admira Seal.


Assuntos
Fluoretos/análise , Selantes de Fossas e Fissuras/química
19.
Clin Exp Med ; 16(4): 503-509, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26319791

RESUMO

Programmed death-1 (PD-1) is one of the most important inhibitory co-receptors expressed predominantly on activated T and B lymphocytes whose expression could be sustained by permanent antigenic stimulation accompanying chronic or recurrent tonsillitis. The expression of PD-1 and PD-1L was analyzed using flow cytometry on hypertrophied tonsils collected from 57 children. We observed high expression of PD-1 and PD-1L on certain lymphocytes subpopulations of hypertrophied tonsils; among T cells, the expression of PD-1 on protein level was higher on CD4+ cells (70.3 %) than on CD8+ cells (35 %). Interestingly, a limited expression of PD-1 was observed on CD19+ B lymphocytes (6.5 %), while CD5+CD19+ B cells overexpressed PD-1 (52.5 %). Moreover, the expression of PD-1L was also higher on CD5+CD19+ B cells (16.5 %) than on CD19+ B cells (3.5 %) and on CD4+ T cells (20 %) than on CD8+ T cells (10 %). PD-1 and PD-1L expressions correlated only on CD5+CD19+ cells. In conclusion, high expression of PD-1 and PD-1L on T and B cells could represent hallmark of immune system adaptation to chronic antigenic exposition in patients with tonsillitis.


Assuntos
Tonsila Faríngea/imunologia , Linfócitos B/metabolismo , Antígeno B7-H1/metabolismo , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Tonsilite/cirurgia , Tonsila Faríngea/metabolismo , Tonsila Faríngea/cirurgia , Adolescente , Antígenos CD19/metabolismo , Linfócitos B/imunologia , Antígenos CD5/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Linfócitos T/metabolismo , Tonsilite/imunologia , Regulação para Cima
20.
Biomed Res Int ; 2016: 4158376, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27840825

RESUMO

Introduction. Polymerization of light-cured dental materials used for restoration of hard tooth tissue may lead to an increase in temperature that may have negative consequence for pulp vitality. Aim. The aim of this study was to determine maximum temperatures reached during the polymerization of selected dental materials, as well as the time that is needed for samples of sizes similar to those used in clinical practice to reach these temperatures. Materials and Methods. The study involved four composite restorative materials, one lining material and a dentine bonding agent. The polymerization was conducted with the use of a diode light-curing unit. The measurements of the external surface temperature of the samples were carried out using the Thermovision®550 thermal camera. Results. The examined materials significantly differed in terms of the maximum temperatures values they reached, as well as the time required for reaching the temperatures. A statistically significant positive correlation of the maximum temperature and the sample weight was observed. Conclusions. In clinical practice, it is crucial to bear in mind the risk of thermal damage involved in the application of light-cured materials. It can be reduced by using thin increments of composite materials.


Assuntos
Cimentos Dentários/síntese química , Cimentos Dentários/efeitos da radiação , Temperatura Alta , Cura Luminosa de Adesivos Dentários/métodos , Polímeros/síntese química , Polímeros/efeitos da radiação , Dureza/efeitos da radiação , Luz , Teste de Materiais
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