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1.
Opt Express ; 29(24): 39042-39054, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809275

RESUMO

We present achromatic frequency doubling of supercontinuum pulses from a hollow core fiber as a technique for obtaining tunable ultrashort pulses in the near UV and blue spectral range. Pulse energies are stable on a 1.1% level, averaged over 100 000 shots. By the use of conventional optics only, we compress a 0.2 µJ pulse at a center wavelength of 475 nm to a pulse duration of 12 fs, as measured by X-FROG. We test the capabilities of the approach by employing the ASHG-pulses as a pump in a transient absorption experiment on ß-carotene in solution.

2.
BMC Cancer ; 21(1): 1018, 2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34511112

RESUMO

BACKGROUND: An effective cross-cultural doctor-patient communication is vital for health literacy and patient compliance. Building a good relationship with medical staff is also relevant for the treatment decision-making process for cancer patients. Studies about the role of a specific migrant background regarding patient preferences and expectations are lacking. We therefore conducted a multicentre prospective survey to explore the needs and preferences of patients with a migrant background (PMB) suffering from gynecological malignancies and breast cancer to evaluate the quality of doctor-patient communication and cancer management compared to non-migrants (NM). METHODS: This multicentre survey recruited patients with primary or recurrence of breast, ovarian, peritoneal, or fallopian tube cancer. The patients either filled out a paper form, participated via an online survey, or were interviewed by trained staff. A 58-item questionnaire was primarily developed in German and then translated into three different languages to reach non-German-speaking patients. RESULTS: A total of 606 patients were included in the study: 54.1% (328) were interviewed directly, 9.1% (55) participated via an online survey, and 36.8% (223) used the paper print version. More than one quarter, 27.4% (166) of the participants, had a migrant background. The majority of migrants and NM were highly satisfied with the communication with their doctors. First-generation migrants (FGM) and patients with breast cancer were less often informed about participation in clinical trials (p < 0.05) and 24.5% of them suggested the help of an interpreter to improve the medical consultation. Second and third-generation migrants (SGM and TGM) experienced more fatigue and nausea than expected. CONCLUSIONS: Our results allow the hypothesis that training medical staff in intercultural competence and using disease-related patient information in different languages can improve best supportive care management and quality of life in cancer patients with migrant status.


Assuntos
Neoplasias da Mama/etnologia , Neoplasias dos Genitais Femininos/etnologia , Motivação , Avaliação das Necessidades , Preferência do Paciente/etnologia , Relações Médico-Paciente , Migrantes , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/psicologia , Comunicação , Assistência à Saúde Culturalmente Competente/etnologia , Feminino , Neoplasias dos Genitais Femininos/psicologia , Alemanha , Letramento em Saúde , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/etnologia , Cooperação do Paciente , Preferência do Paciente/estatística & dados numéricos , Satisfação do Paciente/etnologia , Satisfação do Paciente/estatística & dados numéricos , Estudos Prospectivos , Inquéritos e Questionários , Migrantes/estatística & dados numéricos , Traduções , Adulto Jovem
3.
Ann Oncol ; 27(12): 2236-2241, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27789470

RESUMO

BACKGROUND: Randomized, phase III trial to evaluate safety and efficacy of topotecan and carboplatin (TC) compared with standard platinum-based combinations in platinum-sensitive recurrent ovarian cancer (ROC). PATIENTS AND METHODS: Patients were randomly assigned in a 1:1 ratio to the experimental TC arm (topotecan 0.75 mg/m2/ days 1-3 and carboplatin AUC 5 on day 3 every 3 weeks) or to one of the standard regimes [(PC) paclitaxel plus carboplatin; (GC) gemcitabine plus carboplatin; (PLDC) pegylated liposomal doxorubicin and carboplatin] which could be chosen by individual preference but before randomization. The primary end point was progression-free survival (PFS) after 12 months. Overall survival (OS), response rate, toxicity, quality of life and treatment preference regarding standard treatment were defined as secondary end points. RESULTS: A total of 550 patients were recruited. The PFS rate after 12 months was 37.0% for TC compared with 40.2% in the standard combinations (P = 0.470). The overall response rate was 73.1% for TC versus 75.1% for standard combinations (P = 0.149). After a median follow-up of 20 months, the median PFS was 10 months [95% confidence interval (CI) 9.4-10.6] and did not differ between both arms (P = 0.414). The median OS was 25 months in the TC arm versus 31 months in the standard arm (95% CI: 22.4-27.6 resp. 26.0-36.0; P = 0.163). Severe hematologic toxicities (grade 3/4) were rare in the experimental arm (P < 0.001), with 17.4% leucopenia, 27.8% neutropenia and 15.9% thrombopenia. CONCLUSION: The combination of carboplatin and topotecan was well tolerated with significant lower rates of severe hematological toxicities but did not improve PFS or OS in platinum-sensitive relapsed ovarian cancer compared with established standard regimens.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carboplatina/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Topotecan/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Áustria , Carboplatina/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/análogos & derivados , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/efeitos adversos , Qualidade de Vida , Topotecan/efeitos adversos , Gencitabina
4.
Anaesthesist ; 62(10): 797-807, 2013 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-24057760

RESUMO

BACKGROUND: In view of the development of innovative and non-traumatic surgical techniques, postoperative pain management should be carried out depending on the invasiveness of the intervention. In the present study two analgesic strategies were compared in patients undergoing minimally invasive hysterectomy: epidural analgesia (EDA) and intravenous patient-controlled analgesia (iv-PCA). MATERIAL AND METHODS: For this prospective case controlled study 60 women with benign uterine diseases undergoing vaginal hysterectomy (VH) or laparoscopically assisted vaginal hysterectomy (LAVH) were enrolled. Patients were divided for analysis into two groups (n=30 each) according to the postoperative analgesic strategy (EDA group versus iv-PCA group). A matched-pair analysis was applied (matching criteria: risk assessment, surgeon and age of patient) to minimize the differences between both groups. Patients were evaluated with respect to the extent of pain determined by a numeric rating scale (NRS 0-10 scale), analgesic consumption, rate of postoperative nausea and vomiting (PONV), mobilization from bed, oral intake of nutrition, complications, duration of stay in the recovery room as well as hospital stay and health-related quality of life (SF-36 Health Survey; collected before and 6 weeks after surgery). RESULTS: Laparoscopically assisted removal of the uterus was carried out in 22 women and by vaginal hysterectomy in 38 women. No significant differences between the study groups were seen in the duration of surgery (iv-PCA 58 ± 25 min versus EDA 60 ± 26 min). Demographic data of both groups as well as intraoperative hemodynamic and respiratory parameters were comparable to a great extent. Compared to the iv-PCA group, women in the EDA group showed lower NRS values (p<0.01): recovery room admission 4.7 ± 2.5 iv-PCA vs. 0.9 ± 1.3 EDA, recovery room discharge 3.8 ± 1.8 iv-PCA vs. 1.0 ± 1.2 EDA, day of surgery at 8 p.m. 5.0 ± 2.1 iv-PCA vs. 1.8 ± 2.3 EDA and first postoperative day at 8 a.m. 3.5 ± 1.7 iv-PCA vs. 1.9 ± 2.2 EDA. In addition, less PONV (iv-PCA 9/30 vs. EDA 1/30, p<0.01), less shivering (iv-PCA 8/30 vs. EDA 2/30, p<0.05), reduced fatigue (iv-PCA 26/30 vs. EDA 9/30, p<0.05) and a lower consumption of analgesics were found. Average postoperative requirement for piritramide in the iv-PCA group was 7 mg (range 0-24 mg) on the day of surgery and 5 mg (0-39 mg) on the first postoperative day. In the EDA group no opiate medication was given postoperatively (p<0.01). Duration of stay in the recovery room was shorter in the EDA group (71 ± 32 min vs. 50 ± 13 min, p<0.05). Hospital stay was 5 days on average in both groups. There were no surgical complications or epidural catheter-related complications. Because of urinary retention catheterization of the bladder had to be made in 3 patients of the iv-PCA group and 13 patients of the EDA group (p<0.05). Furthermore, the possibility to take a shower postoperatively was restricted in the EDA group because the epidural catheter was in place and thereby hygiene concerns. Regarding the early oral nutritional intake as well as postoperative mobilization, no significant differences between groups were found. In comparison with the preoperative status, the results regarding health-related quality of life were significantly better for both groups after a follow-up of 6 weeks (p<0.01); however, this effect was especially pronounced in the EDA group (p<0.05). CONCLUSIONS: To reduce the number of patients suffering from postoperative pain a procedure-specific pain management should be developed. The results of this study have shown that even in minimally invasive surgery, such as vaginal hysterectomy and laparoscopically assisted vaginal hysterectomy there are some advantages for epidural analgesia compared to intravenous patient-controlled analgesia. In particular reduced pain intensity, lower need for analgesics and reduced occurrence of PONV can lead to excellent patient comfort, fast recovery as well as positive effects on health-related quality of life. However, there are also some disadvantages such as an increased rate of urinary retention and restriction of mobility.


Assuntos
Analgesia Epidural/métodos , Analgesia Controlada pelo Paciente/métodos , Histerectomia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Manejo da Dor/métodos , Dor Pós-Operatória/terapia , Adulto , Analgésicos/administração & dosagem , Analgésicos/uso terapêutico , Deambulação Precoce , Feminino , Hemodinâmica/fisiologia , Humanos , Laparoscopia , Pessoa de Meia-Idade , Bloqueio Nervoso , Estudos Prospectivos , Qualidade de Vida , Resultado do Tratamento
5.
Gynecol Oncol ; 116(3): 317-22, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19959213

RESUMO

BACKGROUND: For the adjuvant setting of advanced ovarian cancer (AOC) after primary radical surgery the combination of paclitaxel and platinum in a 3-week schedule has emerged as the current standard. In preclinical studies additional anti-angiogenic effects of low dose paclitaxel infusion were demonstrated. A sequential schedule of carboplatin and paclitaxel has the potential to improve the therapeutic index. METHODS: In this multicenter phase II trial four cycles of carboplatin at a dose of AUC 5 (d1/q21d) followed by 12 cycles of weekly paclitaxel at a dose of 80 mg/m(2) (d1/q7d) were applied after primary radical surgery. Eligible were all optimally or sub-optimally debulked patients with FIGO IA-IV ovarian cancer. All patients with hemoglobin levels <12 mg/dl received erythropoietin additionally. RESULTS: Between July 2003 and May 2005, 105 patients from 27 institutions were enrolled. The median age was 60 years (range: 23-80 years). A median number of 16 courses (range 1-16) were applied. The incidence of non-hematological toxicities was very low. Only 41% of patients experienced alopecia (grade 1-2). Neurotoxicity (grade 3-4) was not observed. Grade 3-4 hematological toxicity (43% of all patients) included thrombocytopenia (17%), anemia (3%), leucopenia (23%), and neutropenic fever (0%). Ninety-seven percent received erythropoietin. Thromboembolic events (4%) were not increased in patients who received erythropoietin. After a median time of 23 months (range: 1-42 months) 32 patients had died, and the median overall survival was not reached. The progression-free survival was 25.4 months (95% CI: 18.8-40+). CONCLUSION: These results suggest that this sequential regimen using weekly paclitaxel represents an efficacious and well-tolerated regimen. A randomized study comparing this new schedule with the conventional 3-week protocol is warranted.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Quimioterapia Adjuvante , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/cirurgia , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
6.
Cell Death Differ ; 15(4): 773-82, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18219316

RESUMO

Cellular FLICE-inhibitory protein (c-FLIP) proteins are known as potent inhibitors of death receptor-mediated apoptosis by interfering with caspase-8 activation at the death-inducing signaling complex (DISC). Among the three human isoforms, c-FLIP(long), c-FLIP(short) and c-FLIP(R), the latter isoform is poorly characterized. We report here the characterization of murine c-FLIP(R) and show that it is the only short c-FLIP isoform expressed in mice. By generating several mutants, we demonstrate that both death effector domains (DEDs) are required for DISC binding and the antiapoptotic function of c-FLIP(R). Surprisingly, the C-terminal tail is important for both protein stability and DISC recruitment. Three-dimensional modeling of c-FLIP(R) revealed a substantial similarity of the overall structures and potential interaction motifs with the viral FLIP MC159. We found, however, that c-FLIP(R) uses different structural motifs for its DISC recruitment. Whereas MC159 interferes with interaction and self-oligomerization of the DISC component FADD by its extensive hydrophilic surface, a narrow hydrophobic patch of c-FLIP(R) on the surface of DED2 is crucial for DISC association. Thus, despite the presence of similar tandem DEDs, viral and cellular FLIPs inhibit apoptosis by remarkably divergent mechanisms.


Assuntos
Apoptose , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/metabolismo , Proteínas Adaptadoras de Sinalização de Receptores de Domínio de Morte/metabolismo , Mutação , Sequência de Aminoácidos , Animais , Sítios de Ligação , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/química , Proteína Reguladora de Apoptosis Semelhante a CASP8 e FADD/genética , Caspase 8/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Imageamento Tridimensional , Camundongos , Modelos Moleculares , Dados de Sequência Molecular , Células NIH 3T3 , Complexo de Endopeptidases do Proteassoma/metabolismo , Ligação Proteica , Conformação Proteica , Isoformas de Proteínas/metabolismo , Estrutura Terciária de Proteína , Transfecção , Proteínas Virais/química , Proteínas Virais/metabolismo
7.
Clin Nephrol ; 25(2): 87-93, 1986 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-3516478

RESUMO

In 57 patients with chronic renal failure (CRF) [44 patients on regular dialysis treatment (RDT), 33 renal transplant patients (RT) and 26 normal patients (NP)] and in a further 11 patients with CRF (8 patients on RDT and 17 patients without any renal disease in the post mortem) the vitamin A content of the serum obtained from the tissue of the liver, the stomach, the subcutaneous adipose tissue and the bone were analyzed. The vitamin A content of the serum was increased significantly for all groups of patients in comparison with the control group, but hypervitaminotic ranges were not reached in any case. The vitamin A content decreased depending on the time of dialysis treatment and the period after kidney transplantation. The retinol-binding protein accumulated even more than vitamin A in CRF and RDT. This statement is not in conformity with that of a hypervitaminosis A, of which normal respectively decreased RBP levels are characteristic. The serum prealbumin concentration was near the upper limit of the normal range in all groups of patients. The serum content of beta-carotene in patients with CRF and RDT was raised in comparison with NP and RT patients. As to the vitamin A content of the organs, a distinctive decrease appeared in the liver, so that a marginal supply must be assumed. In the stomach and the subcutaneous adipose tissue no changes, in comparison with the control patients, resulted. Due to renal insufficiency the results indicated an unphysiological situation in the vitamin A metabolism. Connections with disturbances of the fat-household could not be set up.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Falência Renal Crônica/metabolismo , Vitamina A/metabolismo , Adulto , Carotenoides/sangue , Colesterol/sangue , Feminino , Humanos , Hiperparatireoidismo/metabolismo , Falência Renal Crônica/terapia , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Osteomalacia/metabolismo , Pré-Albumina/metabolismo , Diálise Renal , Proteínas de Ligação ao Retinol/sangue , Distribuição Tecidual , Triglicerídeos/sangue , Vitamina A/sangue , beta Caroteno
8.
Clin Nephrol ; 28(5): 244-9, 1987 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-3322620

RESUMO

In the pathogenesis of infectious diseases, great importance is attached to the problem of adhesion of bacteria to cells. In 100 urine specimens from normal test persons, patients with infections of the lower urinary tract, with chronic pyelonephritis and glomerulonephritis were studied. The adhesion of strains of Escherichia coli to human uroepithelial cells depended on the concentration of single urinary factors. While increased concentrations of urea and creatinine favored the adhesion process, a statistically significant negative influence was found with regard to potassium, immunoglobulins and pH value. Considering the multifactorial effects of the urinary constituents, we found in a multivariate comparison that none of the studied physiological features alone exerts a fundamental influence upon adhesion, but in their entirety they determine the environmental conditions for the adhesion of bacteria to cells in the urine.


Assuntos
Aderência Bacteriana/efeitos dos fármacos , Escherichia coli/fisiologia , Glomerulonefrite/urina , Pielonefrite/urina , Sistema Urinário/microbiologia , Adulto , Idoso , Análise de Variância , Glomerulonefrite/microbiologia , Humanos , Pessoa de Meia-Idade , Pielonefrite/microbiologia , Infecções Urinárias/microbiologia
9.
Clin Nephrol ; 57(6): 425-31, 2002 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12078945

RESUMO

BACKGROUND: Postexercise proteinuria, hematuria and changes in serum electrolyte balance as well as increased levels of plasma indicators for muscle leakage are believed to be transient and of benign character. METHODS: A group of 51 healthy athletes took part in a 100 km race over 14.25 hours. All of them had to reach the finish together. Urine and blood samples were collected before (a) and immediately after running (b) as well as 6 hours after the race (c). RESULTS: The serum concentrations of potassium (4.8 +/- 0.5 (a) vs. 4.0 +/- 0.3 (c) mmol/l), protein (73.1 +/- 5.2 (a) vs. 71.1 +/- 3.9 (c) g/l) and albumin (44.0 +/- 2.85 (a) vs. 42.9 +/- 2.8 (c) g/l) decreased significantly (p < 0.0001, p < 0.05, p < 0.05, respectively) but remained within physiological ranges. The serum sodium concentration decreased immediately after the race (136.9 +/- 4.5 (a) vs. 131.1 +/- 2.4 (b) micromol/l, p < 0.0001). The fractional sodium excretion decreased 6 hours, but not immediately after the race (0.78 +/- 0.59 (a) vs. 0.48 +/- 0.82 (c), p < 0.05). Myoglobin (31.8 +/- 6.9 (a), 291.5 +/- 197.2 (b) and 182.2 +/- 135.3 (c) microg/l, p < 0.0001) and creatine kinase (1.13 +/- 0.45 (a), 10.76 +/- 6.9 (b) and 9.46 +/- 15.5 (c) pmol/l, p < 0.0001) increased dramatically. Troponin I was also significantly increased at finish (0.0186 +/- 0.0121 (a) vs. 0.0213 +/- 0.0165 (b) ng/ml, p < 0.05) and positively correlated with myoglobin and creatine kinase, but remained far below the pathologic range. Serum creatinine and urea remained almost unchanged. Glucosuria and hematuria occurred 6 hours after the run in 9.1% and 6.8%, respectively. The erythrocytes examined by phase-contrast microscopy were not damaged in terms of dysmorphic cells. Glomerular-type proteinuria was found in 11.4% of the participants 6 hours after the race. CONCLUSIONS: We conclude that long lasting, mild exertion is harmless for renal function, electrolyte balance and skeletal muscle as well as myocardial metabolism in healthy persons.


Assuntos
Exercício Físico/fisiologia , Nefropatias/fisiopatologia , Rim/fisiopatologia , Células Musculares/fisiologia , Equilíbrio Hidroeletrolítico/fisiologia , Adulto , Feminino , Hemodinâmica/fisiologia , Humanos , Nefropatias/sangue , Nefropatias/urina , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Valores de Referência , Corrida/fisiologia , Fatores de Tempo
10.
Int J Artif Organs ; 5(2): 105-9, 1982 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-7095880

RESUMO

13 patients, who had been subjected to hemoperfusion with Amberlite XAD-4 resin (Haemoresin, Fa. Braun), because of acute intoxications, were examined for the adsorption of bioactive material from the blood. A mean treatment period of four hours at a blood flow rate of 200 ml/min. resulted in a marked thrombocyte decrease by 43% and changes in the concentrations of proteins, complement components C3 and C4 (16-26%) triglycerides (33%), aldosterone (33%) and testosterone (20%). Low molecular weight substances and electrolytes, however, were only slightly or not affected. Thus hemoperfusion system with its poor biocompatibility and inability to remove BUN, electrolytes and water is only suitable for short-term treatment and cannot be used without detailed control of possible side effects and perhaps substitution for treatment of chronic renal or hepatic failure. Hemoperfusion has proved an efficient method of treating various exogenous intoxications. The adsorption of biologically active material from the blood constitutes several side effects which contraindicate long-term treatment, above all of endogenous intoxications such as chronic renal failure and hepatic failure. With the type of adsorber used - various charcoal preparations, resins etc. such as uncoated material or coated with different substances - these side effects vary and have not yet been investigated in a systematic, comparative and comprehensive way. The present investigations are meant to check the adsorption behaviour of Amberlite XAD-4 Resin in vivo towards some selected blood constituents and the influence of hemoperfusion on the concentrations.


Assuntos
Hemoperfusão , Inativação Metabólica , Poliestirenos/uso terapêutico , Polivinil/uso terapêutico , Adolescente , Adulto , Idoso , Proteínas Sanguíneas/análise , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Eletrólitos/sangue , Feminino , Hemoglobinas , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Peso Molecular , Contagem de Plaquetas
11.
Cell Death Differ ; 20(2): 321-32, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23059785

RESUMO

Autophagy is a lysosomal degradation pathway important for cellular homeostasis, mammalian development, cancer and immunity. Many molecular components of autophagy have been identified, but little is known about regulatory mechanisms controlling their effector functions. Here, we show that, in contrast to other p38 MAP kinase activators, the growth arrest and DNA damage 45 beta (Gadd45ß)-MAPK/ERK kinase kinase 4 (MEKK4) pathway specifically directs p38 to autophagosomes. This process results in an accumulation of autophagosomes through p38-mediated inhibition of lysosome fusion. Conversely, autophagic flux is increased in p38-deficient fibroblasts and Gadd45ß-deficient cells. We further identified the underlying mechanism and demonstrate that phosphorylation of the autophagy regulator autophagy-related (Atg)5 at threonine 75 through p38 is responsible for inhibition of starvation-induced autophagy. Thus, we show for the first time that Atg5 activity is controlled by phosphorylation and, moreover, that the spatial regulation of p38 by Gadd45ß/MEKK4 negatively regulates the autophagic process.


Assuntos
Antígenos de Diferenciação/metabolismo , Autofagia , MAP Quinase Quinase Quinase 4/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Antígenos de Diferenciação/genética , Autofagia/efeitos dos fármacos , Proteína 5 Relacionada à Autofagia , Linhagem Celular , Lipopolissacarídeos/toxicidade , Camundongos , Proteínas Associadas aos Microtúbulos/genética , Mutagênese Sítio-Dirigida , Células NIH 3T3 , Fosforilação , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/genética
13.
Clin Res Cardiol ; 95(5): 270-80, 2006 May.
Artigo em Inglês | MEDLINE | ID: mdl-16598393

RESUMO

BACKGROUND: Recently it has been found that BNP and NT-proBNP provide independent prognostic information in patients with acute coronary syndromes (ACS). However, little data are available on the time course of NT-proBNP levels in relation to onset of symptoms. METHODS AND RESULTS: We included 765 patients (236 females, aged 64 +/- 11 years) with an ACS (STEMI 42%, NSTEMI 41%, UAP 17%), who were referred for coronary angiography. NT-proBNP was assessed on admission and the next day. NT-proBNP values were related to the time duration from onset of symptoms until blood drawing with lowest values within 3 h and highest values 24-36 h after onset of symptoms (147 (64-436) pg/ml and 1099 (293-3795) pg/ml, respectively, p < 0.001). Highest values for NT-proBNP on admission were found in patients with NSTEMI compared to patients with STEMI and UAP (912 (310-2258) pg/ml) vs 262 (85-1282) pg/ml) vs 182 (74- 410) pg/ml; p < 0.001), but no difference was present between STEMI and NSTEMI the day after admission (1325 (532-2974) pg/ ml vs 1169 (555-3413) pg/ml; p = 0.676). In contrast NT-proBNP values remained unchanged in UAP (182 (74-410) pg/ml) vs 171 (53-474) pg/ml). CONCLUSION: The time interval from onset of symptoms to first blood collection is an important determinant for NT-proBNP values on admission in patients with an ACS and needs to be considered in clinical practice.


Assuntos
Angina Instável/sangue , Angina Instável/diagnóstico , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Síndrome
14.
Z Kardiol ; 94(11): 742-7, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16258776

RESUMO

Treatment of in-stent restenosis (ISR) remains a therapeutic challenge since many pharmacological and mechanical approaches have shown disappointing results except for brachytherapy. Drug-eluting stents (DES) have been reported to effectively reduce ISR in de novo lesions. We studied 55 consecutive patients with ISR in native coronary arteries and 7 with ISR in saphenous vein grafts (SVG) with elective indication for percutaneous coronary intervention (PCI), who underwent successful implantation with DES. No in-hospital postprocedural major adverse cardiac events were observed. All but one patient (n=61) underwent an angiographic follow-up at 183+/-30 days. Grade of stenosis was assessed by quantitative coronary angiography (QCA) at index procedure and at control angiography. Restenosis (>50%) occurred in 5 patients (8.2%). Target vessel revascularization was performed in an additional 4 patients. Minimal intimal hyperplasia was observed in all segments covered by DES (late loss 0.08+/-0.37 mm, loss index 0.11+/-0.47). One patient suffered from subacute stent thrombosis due to discontinuation of clopidogrel medication. At six month follow-up two patients had died. Death was not related to a restenosis in the treated segment. Conclusion Our experiences with DES treatment of ISR lesions show good angiographic and clinical results at index procedure and at the 6 month follow-up with low sub acute thrombosis rate as compared with existing treatment modalities. Restenosis rate seems to be at least as low as reported for brachytherapy.


Assuntos
Prótese Vascular/efeitos adversos , Reestenose Coronária/tratamento farmacológico , Reestenose Coronária/etiologia , Oclusão de Enxerto Vascular/tratamento farmacológico , Oclusão de Enxerto Vascular/etiologia , Sirolimo/administração & dosagem , Stents/efeitos adversos , Reestenose Coronária/diagnóstico por imagem , Implantes de Medicamento/administração & dosagem , Desenho de Equipamento , Análise de Falha de Equipamento , Feminino , Seguimentos , Oclusão de Enxerto Vascular/diagnóstico por imagem , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Radiografia , Resultado do Tratamento
15.
Exp Pathol ; 39(3-4): 157-64, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2257920

RESUMO

The determinations of enzyme activities in the serum are of considerable importance in detecting xenobiotic effects on the liver. After a brief introduction to the basics of enzyme diagnostics, the enzymes ALAT, ASAT, ICDH, LDH, SDH, GLDH, AP, gamma-GT, CHE are characterized with regard to their occurrence, their half-life periods in the serum and their clinical value. They are followed by enzyme levels and the presentation of the dynamics of enzyme activities in the serum after xenobiotic influences on the liver in humans.


Assuntos
Citosol/enzimologia , Enzimas/sangue , Fígado/efeitos dos fármacos , Xenobióticos/farmacologia , Animais , Canalículos Biliares/enzimologia , Humanos , Fígado/enzimologia , Mitocôndrias Hepáticas/enzimologia , Ribossomos/enzimologia
16.
Appetite ; 20(3): 229-34, 1993 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8373147

RESUMO

The relationship between vegetarianism and the "orthodox" food ideology and the overall food system in the U.K. is complex and ambiguous. Vegetarianism, and a fortiori veganism, appear to represent a direct challenge to orthodox foodways and current production methods. Yet there is some evidence for the incorporation of vegetarianism into the commercial food system, which raises the question of how and why incorporation has occurred.


Assuntos
Dieta Vegetariana , Atitude , Ecologia , Alimentos , Humanos , Princípios Morais , Fenômenos Fisiológicos da Nutrição , Reino Unido
17.
Z Gesamte Inn Med ; 39(11): 261-5, 1984 Jun 01.
Artigo em Alemão | MEDLINE | ID: mdl-6475170

RESUMO

In 8 patients with a slight restriction of the renal function (serum creatinine 150-300 mumol/l), 10 patients with a severe restriction of the renal function (serum creatinine greater than 300-1,200 mumol/l) and in 10 control persons with intact renal function on 2 subsequent days after 40 and 80 mg furosemide the pharmacokinetic data were calculated intravenously from the course of the serum concentration and the renale excretion as well as pharmacodynamic parameters. In comparison to the control persons in patients with creatinine values of more than 200 mumol/l still 4 hours after intravenous injection furosemide could be proved in the serum. According to this the excretion of the unchanged furosemide was clearly decreased in the 24-hour-urine. In decreased renal clearance of furosemide the elimination half-life period was prolonged. In all three groups of patients the diuretic effect of furosemide was very distinctly marked in the first four hours after injection of 40 mg, a doubling of the dose did not increase this effect. Only in the first four hours also an increased excretion of sodium, chloride and calcium occurred; in the 24-hour-collection period no differences between the three groups were the result. The excretion of creatinine and urea-N in the urine was not influenced by furosemide. Thus also in the chronic renal insufficiency there is the indication of the furosemide therapy only then, when the extracellular space or the intravasal volume are enlarged. As individual dose 40 mg are recommended intravenously.


Assuntos
Furosemida/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Testes de Função Renal , Equilíbrio Hidroeletrolítico/efeitos dos fármacos , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Furosemida/sangue , Humanos , Falência Renal Crônica/sangue , Cinética
18.
Int J Clin Pharmacol Ther Toxicol ; 22(9): 481-6, 1984 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-6500766

RESUMO

Three groups of patients with kidney diseases were investigated: I. creatinine in serum less than 100 mumol/l, II. creatinine in serum 100-250 mumol/l, III. creatinine in serum greater than 250 mumol/l. After intravenous injection of 40 mg and 80 mg furosemide, serum concentrations and urinary excretion of the unchanged drug were measured fluorometrically. Moreover, urinary excretion of water, electrolytes, creatinine and urea nitrogen were estimated in order to check the pharmacodynamic effect of the drug. The pharmacokinetic parameters calculated were similar in group I and II. In group III t 1/2 was prolonged, renal clearance of furosemide was diminished. The diuretic effect of furosemide was noticeable during the first 4 hours following the injection of 40 mg in all 3 groups. Doubling the dose did not enhance the effect. Creatinine and urea nitrogen excretion in urine were not influenced by furosemide.


Assuntos
Furosemida/metabolismo , Nefropatias/metabolismo , Creatinina/metabolismo , Diurese/efeitos dos fármacos , Eletrólitos/urina , Furosemida/uso terapêutico , Humanos , Nefropatias/tratamento farmacológico , Falência Renal Crônica/tratamento farmacológico , Falência Renal Crônica/metabolismo , Cinética , Nitrogênio/urina , Ureia/urina
19.
Artigo em Alemão | MEDLINE | ID: mdl-1709905

RESUMO

In 309 patients investigations were made into the functions of blood coagulation with special consideration of numerous metabolic criteria. They referred to 111 healthy control persons and 198 patients with diabetes mellitus, 67 of them being of type I and 131 of type II. From a variety of metabolic characteristics and haemostasis optimal criteria were determined by means of the statistical method of multivariance analysis, which enables a distinction to be made between diabetics of type I, type II and healthy persons. Among those 13 characteristics detected as optimal amount there were thrombin time, thrombin coagulase time as parameter of haemostasis both before and after venous congestion, reptilase time prior to venous congestion and fibrinogen concentration after it. Thus, these coagulation factors indicate a different behaviour in both types of diabetes and in healthy control persons.


Assuntos
Diabetes Mellitus/sangue , Hemostasia , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Criança , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Retinopatia Diabética/sangue , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Valores de Referência
20.
Artigo em Alemão | MEDLINE | ID: mdl-1709906

RESUMO

Various thrombocyte functions and metabolic criteria were investigated in 309 test persons, among them 198 Patients affected with diabetes mellitus, 67 of type I and 131 of type II as well as 111 healthy control persons. From the variety of these factors an optimal amount was determined by means of the statistical method of multivariance analysis separating both types of diabetes and healthy control persons. In addition to haemoglobin A1 concentration, thrombocyte parameters have been found together with the degree of capillary fragility, adrenalin-induced aggregation, platelet aggregation test and clot retraction, which allow individuals to be assigned diagnostically to various groups of test persons. Thus, thrombocyte functions found in both types of diabetes and normal persons exhibit differences which may contribute to a diagnostic classification.


Assuntos
Plaquetas/fisiologia , Diabetes Mellitus/sangue , Adulto , Biomarcadores/sangue , Fragilidade Capilar , Retração do Coágulo , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/sangue , Hemoglobinas Glicadas/análise , Humanos , Análise Multivariada , Agregação Plaquetária , Valores de Referência
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