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941.
Patrizia Caprari Anna Tarzia Giorgio Mojoli Paolo Cianciulli Emilio Mannella Maria Cristina Martorana 《International journal of hematology》2009,89(3):285-293
The implantation of a prosthetic heart valve (HVP) in patients with hereditary spherocytosis (HS) and hereditary elliptocytosis
(HE) is rare, and the changes in the structure and deformability of erythrocytes that follow implantation in these patients
have been poorly described. In the present study, the erythrocytes in HS and HE patients with mechanical HVP were compared
to the erythrocytes in patients with only congenital membrane defects, in terms of biochemical modifications and rheological
behaviour. Integral and cytoskeletal erythrocyte membrane proteins were studied, and blood viscosity (shear rate/shear stress
ratio), aggregation ratio [η(1 s−1)/η(200 s−1)], and red cell visco-elasticity were determined. Valve replacement with a mechanical prosthesis worsened anaemia and resulted
in a change in haemolysis, from sub-clinical to evident. The rheological investigation of erythrocytes from HS patients confirmed
the characteristic increased viscosity and aggregation ratio and the decreased deformability. The rheological behaviour of
erythrocytes from patients with HVP showed a decrease in viscosity and an increase in elastic modulus. In these patients,
the prosthesis seems to have induced traumatic damage to the erythrocyte membrane, leading to fragmentation and lysis, which
in turn modified rheological parameters. The biochemical and rheological investigation allowed us to understand the clinical
and haematological pictures of the patients and to describe the role played by different factors in haemolytic anaemia. 相似文献
942.
Bernabucci U Basiricò L Morera P Lacetera N Ronchi B Nardone A 《Journal of molecular endocrinology》2009,42(2):139-147
Studies have demonstrated that heat shock is associated with alteration in energy metabolism. In this study, we investigated the effect of heat shock on gene expression and secretion of adiponectin and leptin, and gene expression of Hspa2 and Ppargamma in 3T3-L1 adipocytes. Compared with 37 degrees C, adiponectin mRNA was higher at 39 degrees C, and lower at 41 degrees C. Leptin mRNA was higher when adipocytes were exposed to 41 degrees C compared with 37 and 39 degrees C. Secretion of adiponectin increased at 39 degrees C, and when cells were exposed to 41 degrees C it was not detectable. Leptin secretion increased significantly at 41 degrees C, compared with 37 and 39 degrees C. Hspa2 mRNA was increased at 39 degrees C, and the highest level was reached at 41 degrees C. Ppargamma mRNA exhibited a substantial increase in a temperature-dependent manner. The study provides the first evidence of a possible direct effect of heat shock on adiponectin and leptin gene expression and secretion, and demonstrates that the expression of the two adipokines is differentially regulated at the temperatures tested. 相似文献
943.
Gaetano Bertino Annalisa Ardiri Patrizia Maria Boemi Giuseppe Stefano Calvagno Irene Maria Ruggeri Annalisa Speranza Maria Milena Santonocito Dario Ierna Cosimo Marcello Bruno Maria Valenti Roberta Boemi Simona Naimo Sergio Neri 《European journal of clinical pharmacology》2010,66(10):1055-1063
Background
The conventional antiviral treatment of chronic hepatitis related to hepatitis C virus (HCV) often leads to anemia. In this case, it is necessary to reduce ribavirin dose or stop treatment, thus reducing the rate of sustained virological response.Aim
We investigated whether epoetin alpha administration improves treatment adherence and leads to higher percentage of response at the end of therapy and sustained virological response.Methods
Two hundred and fourteen individuals with genotype 1b HCV-related chronic hepatitis underwent treatment with pegylated (peg)-interferon alpha-2A 180 μg once weekly and ribavirin 1,000–1,200 mg/day; 174 were responders. Forty individuals completed treatment with no hemoglobin reduction; 134 developed anemia during therapy. Anemic responders were distributed randomly into two groups: group 1 continued therapy with epoetin alpha addiction; group 2 continued antiviral therapy with ribavirin reduction only.Results
Patients in group 1 achieved better control of hemoglobin levels (13.8?±?1.2 g/dl at the end of therapy) than tthose in group 2 (11.5?±?0.8 g/dl). Sustained virological response was 59.7% in group 1 compared with 34.4% in group 2 (p?<?0.01).Conclusions
In patients with 1b HCV-related chronic hepatitis who develop anemia during antiviral treatment, administration of epoetin alpha increases hemoglobin levels and the end-of-treatment rate and sustains virological response by improving treatment adherence. 相似文献944.
Mattia C.F. Prosperi Maurizio Zazzi Grazia Punzi Laura Monno Grazia Colao Paola Corsi Simona Di Giambenedetto Genny Meini Valeria Ghisetti Stefano Bonora Monica Pecorari Maria Rita Gismondo Patrizia Bagnarelli Tiziana Carli Andrea De Luca for the ARCA Collaborative Group 《Journal of medical virology》2010,82(12):1996-2003
Protease inhibitor (PI)‐resistant HIV‐1 has hardly ever been detected at failed boosted PI‐based first‐line antiretroviral regimens in clinical trials. However, this phenomenon has not been investigated in clinical practice. To address this gap, data from patients starting a first‐line lopinavir/ritonavir (LPV/rtv)‐based therapy with available baseline HIV‐1 RNA load, a viral genotype and follow‐up viral load after 3 and 6 months of treatment were extracted from the Italian Antiretroviral Resistance Cohort Analysis (ARCA) observational database. Based on survival analysis, 39 (7.1%) and 43 (7.8%) of the 548 examined patient cases had an HIV‐1 RNA >500 and >50 copies/ml, respectively, after 6 months of treatment. Cox proportional hazard models detected baseline HIV‐1 RNA (RH 1.79, 95%CI 1.10–2.92 per 1 ? log10 increase, P = 0.02) and resistance to the nucleoside backbone (RH 1.04, 95%CI 1.02–1.06 per 10‐point increase using the Stanford HIVdb algorithm, P < 0.001) as independent predictors of HIV‐1 RNA at >500 copies/ml, but not at the >50 copies/ml cutoff criteria. Higher baseline viral load, older patient age, heterosexual route of infection and use of tenofovir/emtricitabine were predictors of failure at month 3 using the 50‐copy and/or 500‐copy threshold. Resistance to LPV/rtv did not occur or increase in any of the available 36 follow‐up HIV‐1 genotypes. Resistance to the nucleoside backbone (M184V) developed in four cases. Despite the likely differences in patient population and adherence, both the low rate of virological failure and the lack of development of LPV/rtv resistance documented in clinical trials are thus confirmed in clinical practice. J. Med. Virol. 82:1996–2003, 2010. © 2010 Wiley‐Liss, Inc. 相似文献
945.
HMG-CoA reductase inhibitors inhibit rat propylthiouracil-induced goiter by modulating the ras-MAPK pathway 总被引:3,自引:0,他引:3
Laezza C Mazziotti G Fiorentino L Gazzerro P Portella G Gerbasio D Carella C Matarese G Bifulco M 《Journal of molecular medicine (Berlin, Germany)》2006,84(11):967-973
The aim of this study was to evaluate in vivo the antiproliferative effect of an inhibitor of isoprenoids metabolism, lovastatin, in an experimental model of propylthiouracil-induced goiter. In thyroid cells, thyrotropin (TSH)-induced proliferation requires active isoprenoid synthesis, and the HMG-CoA reductase inhibitors have antiproliferative effects in vitro. Propylthiouracil treatment (PTU) of rats led to thyroid hypertrophy and hyperplasia by TSH-induced activation of the mitogen-activated protein kinase (MAPK) pathway. Immunohistochemistry showed an increased number of proliferating cell nuclear antigen (PCNA)-positive cells in the thyroid gland of PTU-treated rats. Moreover, the phosphorylation of ERK1 and ERK2 was increased in the extract from goiter tissue as compared with the thyroid tissue of untreated rats. To determine whether the inhibition of selected pro-survival pathways (i.e., p21ras-MAPK) was sufficient to affect goitrogenesis, thyroids from 12 PTU-treated rats were injected in vivo with an adenovirus transducing a dominant-negative ras gene (Rad-L61.S186) and another set of 12 rats were injected with a pharmacological inhibitor of MAPK (PD98059). Both Rad-L61.S186 and PD98059 were able to inhibit the PTU-induced goiter. It is interesting to note that lovastatin, when administered in drinking water, significantly prevented the thyroid gland enlargement. Therefore, lovastatin-treated thyroid glands were significantly smaller than those treated with PTU alone. In addition, the lovastatin-treated glands also showed a decreased expression of phosphorylated ERK1/2 and a number of PCNA-positive cells. Our data suggest that lovastatin is an efficient inhibitor of goitrogenesis and provide a rationale for innovative therapeutic strategies employing statins in the treatment of nodular goiter in humans.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible for authorized users.Chiara Laezza and Gherardo Mazziotti contributed equally to this paper. 相似文献
946.
947.
Hepatocyte growth factor effects on mesenchymal stem cells: proliferation, migration, and differentiation 总被引:22,自引:0,他引:22
Forte G Minieri M Cossa P Antenucci D Sala M Gnocchi V Fiaccavento R Carotenuto F De Vito P Baldini PM Prat M Di Nardo P 《Stem cells (Dayton, Ohio)》2006,24(1):23-33
Hepatocyte growth factor (HGF), a pleiotropic cytokine of mesenchymal origin promoting migration, proliferation, and survival in a wide spectrum of cells, can also modulate different biological responses in stem cells, but the mechanisms involved are not completely understood so far. In this context, we show that short-term exposure of mesenchymal stem cells (MSCs) to HGF can induce the activation of its cognate Met receptor and the downstream effectors ERK1/2, p38MAPK, and PI3K/Akt, while long-term exposure to HGF resulted in cytoskeletal rearrangement, cell migration, and marked inhibition of proliferation through the arrest in the G1-S checkpoint. When added to MSCs, the K252A tyrosine kinase inhibitor prevented HGF-induced responses. HGF's effect on MSC proliferation was reversed by p38 inhibitor SB203580, while the effects on cell migration were abrogated by PI3K inhibitor Wortmannin, suggesting that HGF acts through different pathways to determine its complex effects on MSCs. Prolonged treatment with HGF induced the expression of cardiac-specific markers (GATA-4, MEF2C, TEF1, desmin, alpha-MHC, beta-MHC, and nestin) with the concomitant loss of the stem cell markers nucleostemin, c-kit, and CD105. 相似文献
948.
Relationship between migraine and epilepsy in pediatric age 总被引:2,自引:0,他引:2
Piccinelli P Borgatti R Nicoli F Calcagno P Bassi MT Quadrelli M Rossi G Lanzi G Balottin U 《Headache》2006,46(3):413-421
OBJECTIVE: Many studies have supported the hypothesis of alteration of cortical hyperexcitability as a possible pathological mechanism underlying the onset of migraine and epileptic attacks. Different biochemical pathways involving cellular structures may increase or decrease the excitability of neuronal membranes. The aim of this study was to identify a possible link between migraine and epilepsy from a clinical and neurophysiologic point of view. METHODS: One-hundred thirty-seven children and adolescents consecutively diagnosed for tension-type headache and idiopathic migraine with and without aura were studied. Anamnestic, clinical, and instrumental data were collected by a neurological examination, a specific questionnaire, and awake electroencephalogram (EEG) registrations. EEG features of nonheadache and nonseizures control group were compared. RESULTS: Fourteen cases (10.2%) had a positive history for seizures with fever, isolated seizures, or epilepsy. Distribution differed according to headache diagnosis; migraine with aura (MWA) was largely prevalent. Specific electroencephalographic abnormalities were present in 11.7% of the sample, with a significant different distribution across the groups of children with headache and the control group: specific interictal abnormalities were found in 10 of 23 (43.5%) children with MWA. Two factors, seizures and specific interictal electroencephalographic abnormalities, showed a different distribution in patients with MWA compared to other classes of headache and control group (P < or = .01). CONCLUSION: The present study supports the hypothesis of a possible clinical continuum between some types of MWA and epileptic syndromes as entities due to altered neuronal excitability with similar genetic substrates. 相似文献
949.
Recombinant human erythropoietin improves angiogenesis and wound healing in experimental burn wounds 总被引:3,自引:0,他引:3
Galeano M Altavilla D Bitto A Minutoli L Calò M Lo Cascio P Polito F Giugliano G Squadrito G Mioni C Giuliani D Venuti FS Squadrito F 《Critical care medicine》2006,34(4):1139-1146
OBJECTIVE: Erythropoietin interacts with vascular endothelial growth factor (VEGF) and stimulates endothelial cell mitosis and motility; thus it may be of importance in the complex phenomenon of wound healing. The purpose of this study was to investigate the effect of recombinant human erythropoietin (rHuEPO) on experimental burn wounds. DESIGN: Randomized experiment. SETTING: Research laboratory. SUBJECTS: C57BL/6 male mice weighing 25-30 g. INTERVENTIONS: Mice were immersed in 80 degrees C water for 10 secs to achieve a deep-dermal second degree burn. Animals were randomized to receive either rHuEPO (400 units/kg/day for 14 days in 100 microL subcutaneously) or its vehicle alone (100 microl/day distilled water for 14 days subcutaneously). On day 14 the animals were killed. Burn areas were used for histologic examination, evaluation of neoangiogenesis by immunohistochemistry, and expression (Western blot) of the specific endothelial marker CD31 as well as quantification of microvessel density, measurement of VEGF wound content (enzyme-linked immunosorbent assay), expression (Western blot) of endothelial and inducible nitric oxide synthases, and determination of wound nitric oxide (NO) products. MEASUREMENTS AND MAIN RESULTS: rHuEPO increased burn wound reepithelialization and reduced the time to final wound closure. These effects were completely abated by a passive immunization with specific antibodies against erythropoietin. rHuEPO improved healing of burn wound through increased epithelial proliferation, maturation of the extracellular matrix, and angiogenesis. The hematopoietic factor augmented neoangiogenesis as suggested by the marked increase in microvessel density and by the robust expression of the specific endothelial marker CD31. Furthermore, rHuEPO enhanced the wound content of VEGF caused a marked expression of endothelial and inducible nitric oxide synthases and increased wound content of nitric oxide products. CONCLUSIONS: Our study suggests that rHuEPO may be an effective therapeutic approach to improve clinical outcomes after thermal injury. 相似文献
950.
Amodeo R De Ponti A Sorbara L Imperatore PF Berizzi M Di Rocco E Saltarel I Marigliani C Avanzini F 《Assistenza infermieristica e ricerca : AIR》2006,25(3):170-175
In spite of the broad recognition of the importance of health education, time for structured one-to -one initiatives of health education during the hospital stay is limited. The organization of an health education meeting for patients admitted to CCU for an acute coronary event is described. METHODS: The planning and implementation of the initiative lasted two years and involved 7 nurses and one doctor. The organization required efforts related to the event itself (preparation of training aids, identification or contents and methods for delivery) but also organizative changes. Dietitians in fact had to be involved because the healthy diet recommended was different from the hospital diet. The assessment of the effectiveness of the health education was also planned: administration of a questionnaire to explore lifestyles and knowledge of the illness before and after the meeting; phone interviews after 3, 6 and 12 months from the meeting. RESULTS: Since may 2003, in the first 3 years 74 meetings have been organised, involving 507 patients and 329 relatives. Each meeting lasts 2 hours and contents delivered encompass the coronary event, risk factors and their modification, healthy lifestyles. Initial preliminary results on the impact of the meeting on lifestyle changes are promising. Initiatives are ongoing to include this activity among officially recognised nursing activities. 相似文献