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1.
J Clin Case Rep ; 2(1): 1-4, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36712142

RESUMO

While immune checkpoint inhibitors (ICIs) are improving outcomes for many cancers, they can have severe adverse effects. Though cardiac immune-related adverse effects (irAEs) are rare, they have considerable morbidity and mortality. Prior case studies have demonstrated successful treatment of ICI induced autoimmune myocarditis with a variety of immunosuppressive regimens. This case describes steroid-refractory autoimmune myocarditis after treatment with pembrolizumab. Treatment with equine anti-thymocyte globulin, a regimen previously documented to reverse ICI induced autoimmune myocarditis, temporarily improved clinical status and cardiac biomarkers, however eventually failed to prevent progression to heart failure and cardiovascular death. This case highlights the importance of early stress-dose steroids, identifies troponin as a potential marker of treatment response, and underscores the value of collaboration between oncology and cardiology for optimal management.

2.
J Eukaryot Microbiol ; 65(6): 783-791, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29611243

RESUMO

The redescription of Opalina undulata Nie 1932, collected from the rectum of the frog Fejervarya limnocharis, is presented in this paper based on detailed morphological information and molecular data. Our results revealed that specimens collected from Diaocha Lake in late August were larger and had more nuclei than those collected from the same site in early May. We sequenced their SSU rDNA-ITS1-5.8S rDNA-ITS2-LSU rDNA (5' end) and found that they were completely identical, which means that the two populations belonged to the same species. These facts gave us a hint that body dimension and number of nuclei are not reliable taxonomic parameters for opalinids during their life cycle. Therefore, we recommended that the specific identification of opalinids based on morphological features should be carried out during seasons except spring. Meanwhile, our molecular phylogenetic analysis confirmed the monophyly of Opalinata. Within Opalinata, Opalinea were monophyletic with all opalinid species grouping together. Karotomorpha and Proteromonas did not group together confirming the paraphyly of Proteromonadea.


Assuntos
Anuros/parasitologia , Estramenópilas/classificação , Estramenópilas/citologia , Estramenópilas/genética , Animais , Sequência de Bases , China , DNA Ribossômico/química , DNA Ribossômico/classificação , DNA Ribossômico/genética , Estágios do Ciclo de Vida , Filogenia , Subunidades Ribossômicas/química , Subunidades Ribossômicas/classificação , Subunidades Ribossômicas/genética , Análise de Sequência de DNA
3.
Epidemiol Mikrobiol Imunol ; 66(1): 15-23, 2017.
Artigo em Tcheco | MEDLINE | ID: mdl-28374594

RESUMO

OBJECTIVE: Interestingly, evidence is currently emerging that the activation of angiogenesis leads to immunomodulatory/immunosuppressive effects both at the local and systemic levels. These are very complex and interconnected processes. In this study, our aim was to establish interferon alpha-2b as an anti-angiogenic agent and show the complexity of angiogenesis and immunomodulation through the serum levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 8 (MMP-8) in high-risk resected malignant melanoma before and after adjuvant therapy with high-dose interferon alpha-2b (HDI). Clinical outcomes of patients were also evaluated. MATERIAL AND METHODS: We prospectively measured the serum levels of VEGF and MMP-8 by ELISA in 29 patients with high-risk resected malignant melanoma receiving adjuvant HDI. Blood samples were collected before and within one week after the treatment. RESULTS: To see the results clearly, we divided our patients into two groups. The first group of patients whose VEGF serum level decreased after HDI (66%) showed long-term complete remission. The mean VEGF serum level in these patients decreased from 779.4 pg/ml to 446.2 pg/ml. This downward trend in VEGF was statistically significant. The second group of patients who did not show a decrease in VEGF serum level after HDI (34%) had no clinical benefit from the treatment. The mean VEGF serum levels in group 2 patients were 408 pg/ml before the treatment and 500 pg/ml after HDI. Results for MMP-8 were ambivalent. CONCLUSIONS: Non-specific immunotherapy with interferons reduces angiogenesis. Our results are in line with the current view of the interconnection and complexity of angiogenesis and immunomodulation/immunosuppression. Non-specific immunotherapy with interferons disrupts the immunosup-pressive effect of the angiogenesis on the development of immune response against tumours and supports anti-tumour response in both direct and indirect way. The interference of HDI with the activation of angiogenesis and tumour progression could explain good clinical outcomes of patients with a decrease in serum VEGF. The outcomes of MMP-8 are inconclusive, its role remain unclear, and MMP-8 does not seem to function as a tumour suppressor.


Assuntos
Interferons , Metaloproteinase 8 da Matriz , Melanoma , Neoplasias Cutâneas , Fator A de Crescimento do Endotélio Vascular , Humanos , Imunoterapia , Interferons/uso terapêutico , Metaloproteinase 8 da Matriz/sangue , Melanoma/sangue , Melanoma/fisiopatologia , Melanoma/terapia , Fator A de Crescimento do Endotélio Vascular/sangue
4.
Eur J Protistol ; 58: 152-163, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28314219

RESUMO

The morphological revisions of Macrocytopharynxa pyriformis (Nie, 1932) Li et al., 2002; collected from the rectum of Fejervarya limnocharis (=Rana limnocharis), are presented in this paper: (1) two surfaces of the organism are not identical - left side narrower and convex, right broader and flat or slightly concave; (2) infundibulum is large and well-developed with no "fold" or "plicature" present in the middle or posterior portion; (3) micronucleus is tiny and ovoid shaped and always embedded in the middle concavity of macronucleus, which can be well revealed by ammoniacal silver staining. Our phylogenetic analysis based on SSU-rDNA showed that M. pyriformis fell into the Nyctotheroides clade, within which four definite Nyctotheroides species were involved - N. cordiformis, N. deslierresae, N. parvus and N. hubeiensis. In combination with their morphological features, we discussed the reliability of using karyophore organelles or kinetal suture patterns as the generic taxonomic criteria. Besides, we considered that the genus Macrocytopharynxa is a junior synonym of Nyctotheroides and we transfer its type species to Nyctotheroides as Nyctotheroides pyriformis n. comb. The phylogenetic pattern of the family Nyctotheridae was also indicated in our work, but it will be necessary to analyze more species from fishes and reptiles before coming to a sound conclusion.


Assuntos
Anuros/parasitologia , Cilióforos/classificação , Animais , Cilióforos/genética , Cilióforos/ultraestrutura , DNA Ribossômico/genética , Microscopia Eletrônica de Varredura , Filogenia , Especificidade da Espécie
5.
J Eukaryot Microbiol ; 63(6): 751-759, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27096441

RESUMO

The morphology of Nyctotheroides hubeiensis (Acta Hydrobiol. Sin. 1998, 22(suppl.):187), collected from the rectum of Phelophylax nigromaculatus, is presented in this paper based on detailed morphological information and molecular data. Our phylogenetic analysis showed that N. hubeiensis fell into the Nyctotheroides clade, which was strongly supported as monophyletic and clustered as basal to the genera Nyctotherus and Clevelandella. Also, the monophyly of the Order Clevelandellida and the affinity of parasitic nyctotherids and free-living metopids were indicated in our work. The origin of clevelandellid ciliates as well as their possible evolutionary history was also discussed here; however, the analysis of more species from other vertebrate hosts (fish, reptiles) should be made before a well-supported conclusion can be drawn.


Assuntos
Anuros/parasitologia , Cilióforos/crescimento & desenvolvimento , Cilióforos/isolamento & purificação , Filogenia , Animais , Cilióforos/classificação , Cilióforos/genética , DNA de Protozoário/genética , DNA Ribossômico/genética
6.
Eur J Protistol ; 51(5): 425-36, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26322499

RESUMO

The ciliate, Buxtonella sulcata, was isolated from a bull cow near Tisnov, Czech Republic, and fixed for light (LM), scanning electron (SEM) and transmission electron microscopic (TEM) study. Presented here are the basic morphometrics from LM study, and the fine-structure of both somatic and vestibular ciliary, and other structures. While many morphological features are similar to ciliates belonging to the order Vestibuliferida, some differences have been discovered, and are presented here. Especially emphasized are the microtubular and fibrilar components of the basic kinetid structures for both somatic and vestibular regions of these protists. Also observed in both TEM and SEM samples were enigmatic membrane bulges at the base of many somatic cilia. These ciliates are seen to have abundant endocytoplasmic bacteria, as seen in LM and TEM. This evaluation of the ultrastructural morphology of B. sulcata from cattle is accompanied by detailed determination of its small subunit rRNA (SSU rRNA) gene sequence and also of internal transcribed spacers (ITS1-5.8rRNA-ITS2). All of these data will contribute to unravel the phylogenetic relationships of medically and veterinary important intestinal ciliates.


Assuntos
Filogenia , Animais , Bovinos , Cilióforos/classificação , Cilióforos/genética , Cilióforos/ultraestrutura , República Tcheca , DNA de Protozoário/genética , DNA Espaçador Ribossômico/genética , Genes de RNAr/genética , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Dados de Sequência Molecular , Especificidade da Espécie
7.
Parasitol Res ; 113(12): 4327-33, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25339517

RESUMO

We obtained sequences of the small subunit ribosomal RNA (rRNA) for two new isolates of Balantidium from fishes, Balantidium polyvacuolum and Balantidium ctenopharingodoni. This is the first introduction of molecular data of Balantidium species from fish hosts in the phylogenetic analyses of the ciliate subclass Trichostomatia. Despite the fact that these species share morphological characteristics common to other species of Balantidium, the phylogenetic analysis of their sequences has shown that they are to be placed in a different branch closely related to the so-called Australian clade. Thus, our results indicate that the genus Balantidium is polyphyletic and possibly should be represented by two different genera; however, the analysis of more species from other poikilothermic hosts (amphibians, reptiles) should be made before a revised taxonomical proposal could be made.


Assuntos
Balantidíase/veterinária , Balantidium/classificação , Doenças dos Peixes/parasitologia , Animais , Balantidíase/parasitologia , Balantidium/genética , Balantidium/isolamento & purificação , Sequência de Bases , DNA de Protozoário/química , DNA de Protozoário/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Peixes , Dados de Sequência Molecular , Filogenia , Subunidades Ribossômicas Menores/genética , Análise de Sequência de DNA/veterinária
8.
Acta Parasitol ; 59(3): 413-9, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25119354

RESUMO

A detailed description of the fine structure of Balantidium ctenopharyngodoni Chen, 1955 with an emphasis on its vestibulum is given in the present paper. As to the vestibular kinetids, special attention is paid to the characters of T1, T2 microtubules and nematodesmata. Serving as the major skeleton to the vestibular cortex, the T1, T2 and Pc microtubules are described herein and their support function is also discussed. Moreover, the well-developed nematodesmata of the vestibular kinetids that form a large basket-like complex are described in detail.


Assuntos
Balantidíase/veterinária , Balantidium/ultraestrutura , Corpos Basais/ultraestrutura , Carpas/parasitologia , Doenças dos Peixes/parasitologia , Microtúbulos/ultraestrutura , Animais , Balantidíase/parasitologia , Balantidium/classificação , Balantidium/isolamento & purificação , China , Microscopia Eletrônica de Transmissão/veterinária
9.
PLoS Negl Trop Dis ; 7(3): e2140, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23556024

RESUMO

Balantidiasis is considered a neglected zoonotic disease with pigs serving as reservoir hosts. However, Balantidium coli has been recorded in many other mammalian species, including primates. Here, we evaluated the genetic diversity of B. coli in non-human primates using two gene markers (SSrDNA and ITS1-5.8SDNA-ITS2). We analyzed 49 isolates of ciliates from fecal samples originating from 11 species of captive and wild primates, domestic pigs and wild boar. The phylogenetic trees were computed using Bayesian inference and Maximum likelihood. Balantidium entozoon from edible frog and Buxtonella sulcata from cattle were included in the analyses as the closest relatives of B. coli, as well as reference sequences of vestibuliferids. The SSrDNA tree showed the same phylogenetic diversification of B. coli at genus level as the tree constructed based on the ITS region. Based on the polymorphism of SSrDNA sequences, the type species of the genus, namely B. entozoon, appeared to be phylogenetically distinct from B. coli. Thus, we propose a new genus Neobalantidium for the homeothermic clade. Moreover, several isolates from both captive and wild primates (excluding great apes) clustered with B. sulcata with high support, suggesting the existence of a new species within this genus. The cysts of Buxtonella and Neobalantidium are morphologically indistinguishable and the presence of Buxtonella-like ciliates in primates opens the question about possible occurrence of these pathogens in humans.


Assuntos
Balantidíase/veterinária , Balantidium/classificação , Balantidium/genética , Variação Genética , Doenças dos Primatas/parasitologia , Animais , Animais Domésticos , Animais Selvagens , Balantidíase/parasitologia , Balantidium/isolamento & purificação , Análise por Conglomerados , DNA de Protozoário/química , DNA de Protozoário/genética , DNA Ribossômico/química , DNA Ribossômico/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , Genes de RNAr , Dados de Sequência Molecular , Filogenia , Primatas , RNA de Protozoário/genética , RNA Ribossômico 18S/genética , Análise de Sequência de DNA
10.
J Eukaryot Microbiol ; 60(1): 37-43, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23190245

RESUMO

Two isolates of the pycnotrichid ciliate genus, Vestibulongum, were collected from the host fish, Acanthurus xanthopterus, from two locations in the Southern Pacific Ocean. One was from the Great Barrier Reef (GBR), and a second from Papua New Guinea. These sites are thousands of km from the type locality, off the coast of South Africa. New data were collected from protargol-stained samples to more fully characterize the general form and light microscopic structures of the ciliate. Specimens from all three sites had a long vestibule, characteristic of most members of the family. Data suggest that specimens from each site are the same genus. The kinetids of the Vestibulongum isolated from the GBR contained the typical components of postciliary, transverse, and nemodesmatal microtubules, and Kd fibrils. Also, two quite different forms of endomacronuclear bacteria were observed and are described. One of those has distinct endospores, which are similar to endospores in nuclear endosymbiotic bacteria in a species of Balantidium from the gut of another species of surgeonfish.


Assuntos
Fenômenos Fisiológicos Bacterianos , Perciformes/parasitologia , Simbiose , Trichostomatina/citologia , Trichostomatina/fisiologia , Animais , Austrália , Especificidade de Hospedeiro , Microscopia Eletrônica de Transmissão , Papua Nova Guiné , Queensland , Água do Mar/parasitologia , Proteínas de Prata/química , África do Sul , Trichostomatina/microbiologia , Trichostomatina/ultraestrutura
11.
Folia Biol (Praha) ; 58(5): 185-92, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23249637

RESUMO

The aim of this study was to evaluate preoperative tumour expression of NAD(P)H:quinone oxidoreductase 1 (NQO1) along with other biological markers as potential predictors of pathological complete response (pCR) to neoadjuvant docetaxel, doxorubicin, and cyclophosphamide-containing (TAC) chemotherapy in patients with primary breast cancer. Sixty-one patients who received neoadjuvant chemotherapy (NCT) with TAC regimen were enrolled in this prospective study. The pre- and post- NCT expression of oestrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor 1 and 2 (EGFR and HER2), NQO1, Ki-67 proliferation index, multidrug resistance protein 1 (MDR1), p53 and BCL2 were evaluated by immunohistochemistry. The pCR was reached in 14 patients (23 % of the study group). Multivariate analysis demonstrated that patients with ER-, PR-, NQO1- negative, and Ki-67-positive tumours had a significantly higher chance to achieve pCR. Within the biological subtypes, the highest pCR rate (50 %) was seen in triple-negative (i.e. ER-, PR-, HER2-) tumours. Post-operative evaluation showed that in comparison to pre-operative tissue samples, NQO1 expression was significantly increased, while Ki-67 and HER2 decreased, in the residual tissue after NCT. In conclusion, the present data suggests that NQO1 expression may be a novel diagnostic biomarker for the prediction of positive response to NCT in patients with breast cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , NAD(P)H Desidrogenase (Quinona)/metabolismo , Terapia Neoadjuvante , Antígenos de Neoplasias/imunologia , Neoplasias da Mama/enzimologia , Neoplasias da Mama/imunologia , Feminino , Humanos , Imuno-Histoquímica , Resultado do Tratamento
12.
Cancer Invest ; 30(9): 663-78, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23020282

RESUMO

Neoadjuvant chemotherapy (NCT) of breast cancer enabled improved outcomes especially in patients with advanced and inflammatory diseases. Biological heterogeneity of these tumors, however, requires better molecular characterization of the malignant tissue with consequent individualization in the selection of appropriate agents. To date, numerous molecular markers have been identified, and some of them (e.g., measurement of hormonal or growth factors receptors) are already routinely used for breast cancer classification before NCT. In the present article, we summarize current knowledge about established as well as promising biomarkers which have demonstrated prognostic or predictive value in NCT of breast cancer.


Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias da Mama/imunologia , Neoplasias da Mama/metabolismo , Quimioterapia Adjuvante , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Humanos , Antígeno Ki-67/análise , Prognóstico , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Taxoides/uso terapêutico , Trastuzumab
13.
Klin Onkol ; 24(3): 180-6, 2011.
Artigo em Tcheco | MEDLINE | ID: mdl-21717787

RESUMO

BACKGROUNDS: The incidence of malignant melanoma is increasing by about 2-5% per year, exceeding an incidence of all other tumors. Adjuvant immunotherapy with high-dose interferon (HDI) as per the ECOG 1684 trial Kirkwood's schema is still recommended as a standard. HDI should be started within 60 days after a surgical procedure. Meaningful adjuvant immunotherapy is based on radical surgical excision, an investigation of the sentinel node and regional lymph node dissection, if indicated. Current research aims to utilize routinely usable biomarkers in order to define patients who would explicitly profit from HDI. DESIGN: The authors present a review of HDI trials, focusing on the management of adverse effects of HDI and on biomarkers. This review also discusses the initial own experiences at the Oncology Centre in Hradec Králové. CONCLUSION: Malignant melanoma is a very immunogenic tumour. Immunotherapy with HDI is considered to be the only therapeutic modality so far that has been proven to prolong relapse-free survival and overall survival (in short-time criterion) in adjuvant setting. However, the results of these trials are inconsistent and particular biomarkers of therapeutic response have not been defined yet.


Assuntos
Antineoplásicos/administração & dosagem , Biomarcadores Farmacológicos/análise , Interferon-alfa/administração & dosagem , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Antineoplásicos/efeitos adversos , Humanos , Imunoterapia , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Melanoma/imunologia , Prognóstico , Proteínas Recombinantes , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/imunologia
14.
Aliment Pharmacol Ther ; 32(9): 1091-101, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20804454

RESUMO

BACKGROUND: Nonsteroidal anti-inflammatory drugs are associated with upper gastrointestinal mucosal injury. Naproxen etemesil is a lipophilic, non-acidic, inactive prodrug of naproxen that is hydrolysed to pharmacologically active naproxen once absorbed. We hypothesized that with lesser topical exposure to naproxen from the prodrug, there would be reduced gastroduodenal mucosal injury compared with naproxen. AIM: To compare the degree of endoscopic mucosal damage of naproxen etemesil vs. naproxen. METHODS: This multicentre, randomized, double-blind, double-dummy trial compared oral naproxen etemesil 1200 mg twice daily (n = 61) with naproxen 500 mg twice daily (n = 59) for 7.5 days in 120 healthy subjects (45-70 years; mean 51 years; 58% female) with baseline total modified gastroduodenal Lanza score ≤ 2 (no erosions/ulcers) on endoscopy. The primary endpoint was mean total modified gastroduodenal Lanza score on day 7. A secondary endpoint was incidence of gastric ulcers. RESULTS: The day 7 mean total modified gastroduodenal Lanza score was 2.8 ± 1.7 for naproxen etemesil vs. 3.5 ± 2.0 for naproxen (P = 0.03), and significantly fewer naproxen etemesil-treated subjects (3.3%) developed gastric ulcers compared with naproxen-treated subjects (15.8%) (P = 0.02). CONCLUSION: In this first proof-of-concept study, naproxen etemesil was associated with significantly lower gastroduodenal mucosal injury compared with naproxen after 7 days of exposure ( CLINICAL TRIAL NUMBER: NCT00750243).


Assuntos
Anti-Inflamatórios não Esteroides/efeitos adversos , Mucosa Gástrica/efeitos dos fármacos , Naproxeno/efeitos adversos , Pró-Fármacos/efeitos adversos , Úlcera Gástrica/induzido quimicamente , Idoso , Método Duplo-Cego , Endoscopia Gastrointestinal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
J Exp Biol ; 213(3): 445-52, 2010 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-20086129

RESUMO

Cold acclimation of ectotherms results typically in enhanced oxidative capacities and lipid remodeling, changes that should increase the risk of lipid peroxidation (LPO). It is unclear whether activities of antioxidant enzymes may respond in a manner to mitigate the increased potential for LPO. The current study addresses these questions using killifish (Fundulus heteroclitus macrolepidotus) and bluegill (Lepomis macrochirus) acclimated to 5 and 25 degrees C for 9 days and 2 months, respectively. Because the effects of temperature acclimation on pro- and antioxidant metabolism may be confounded by variable activity levels among temperature groups, one species (killifish) was also subjected to a 9-day exercise acclimation. Oxidative capacity of glycolytic (skeletal) muscle (indicated by the activity of cytochrome c oxidase) was elevated by 1.5-fold in killifish, following cold acclimation, but was unchanged in cardiac muscle and also unaffected by exercise acclimation in either tissue. No changes in citrate synthase activity were detected in either tissue following temperature acclimation. Enzymatic antioxidants (catalase and superoxide dismutase) of either muscle type were unaltered by temperature or exercise acclimation. Mitochondria from glycolytic muscle of cold-acclimated killifish were enriched in highly oxidizable polyunsaturated fatty acids (PUFA), including diacyl phospholipids (total carbons:total double bonds) 40:8 and 44:12. Increased oxidative capacity, coupled with elevated PUFA content in mitochondria from cold-acclimated animals did not, however, impact LPO susceptibility when measured with C11-BODIPY. The apparent mismatch between oxidative capacity and enzymatic antioxidants following temperature acclimation will be addressed in future studies.


Assuntos
Aclimatação/fisiologia , Antioxidantes/metabolismo , Peixes/fisiologia , Peroxidação de Lipídeos/fisiologia , Lipídeos de Membrana/metabolismo , Músculos/enzimologia , Temperatura , Animais , Fundulidae/fisiologia , Masculino , Microssomos/metabolismo , Membranas Mitocondriais/metabolismo , Oxirredução , Fosfolipídeos/metabolismo
16.
Eur J Protistol ; 45(3): 174-82, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19251405

RESUMO

Members of the ciliate genus Balantidium possess a specialized "Villeneuve-Brachon's" field of somatic cilia to the right of the vestibule, or in a dextroral location. Specimens of the type species were collected in Italy and fixed for study by light microscopy, and scanning and transmission electron microscopy. The presence of the field in the type species and several other species of the genus indicates a need to re-describe the genus by including details of the ultrastructure of that field. Scanning electron microscopy shows that the field consists of one row of relatively short cilia of uniform length flanked on each side by 2-3 rows, or more, of very short cilia. Their kinetids have typical litostome structure in transmission electron micrographs. We speculate on a possible function for the Villeneuve-Brachon's field and also present morphometric data on the type species. The base sequence of the small subunit ribosomal RNA gene of Balantidium entozoon has been determined and found to differ by 5% from that of B. coli. Based on the location and ultrastructure, organelles found around the somatic kinetosomes and within inter-kinetal ridges of B. entozoon were identified as hydrogenosomes.


Assuntos
Balantidium/classificação , Balantidium/ultraestrutura , Animais , Balantidium/genética , Análise por Conglomerados , DNA de Protozoário/química , DNA de Protozoário/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Genes de RNAr , Itália , Microscopia , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Dados de Sequência Molecular , Organelas/ultraestrutura , Filogenia , RNA de Protozoário/genética , RNA Ribossômico 18S/genética , Análise de Sequência de DNA
17.
J Eur Acad Dermatol Venereol ; 22(1): 19-24, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18031504

RESUMO

BACKGROUND: Clinical studies of low-dose oral methotrexate (MTX) in the treatment of psoriasis and rheumatoid arthritis document a large interpatient variability in the pharmacokinetics of MTX, including its polyglutamates (MTXPGs) in erythrocytes (RBC). This can be a factor contributing to the variability of therapeutic and toxic effects. AIM: This pilot trial aimed to investigate the MTXPG concentrations in RBC as well as their relation to therapeutic and adverse effects during the initial 4 months of pharmacokinetically guided therapy with a divided-dose schedule (three doses of MTX separated by 12-h intervals once a week). SUBJECTS AND METHODS: Sixteen psoriatic patients (4 men and 12 women; mean age, 53 years; range, 28-69 years) with moderate-to-severe chronic plaque psoriasis [mean Psoriasis Area and Severity Index (PASI) = 24; range, 9-42] were enrolled in the study. Concentrations of plasma MTX and that of MTXPGs in RBC were assayed using liquid chromatography methods. The area under the concentration-time curve of plasma MTX in the interval 0-8 h post-dose (AUC(0-8 h)) was measured after a test bolus dose of 10 mg, and the starting weekly dose was individualized in order to achieve the target AUC(0-8 h) of 1800 nmol.h/L. The PASI, biochemistry, and haematology tests and MTXPGs levels in RBC were evaluated at baseline and at 4-week intervals. RESULTS: The AUC(0-8 h )achieved 1360 +/- 425 nmol.h/L (mean +/- SD: range, 778-2400 nmol.h/L). The mean (range) of individualized doses was 14.5 mg/week (7.5-22.5 mg). The mean (SD) steady-state concentration of total MTXPGs observed between days 85 to 110 reached 113 (34.6) nmol/L (range, 66.1-174 nmol/L). The PASI decreased from 24.0 +/- 8.0 (mean +/- SD) at baseline to 8.0 +/- 6.1 at day 110 (P < 0.001). Thirteen patients (87%) achieved a greater than 50% improvement in baseline PASI, and seven (47%) experienced a greater than 75% improvement. There was no relationship between the percent improvement from baseline PASI and the steady-state concentration of MTXPGs in RBC. All patients tolerated MTX well. Throughout the study period, there was a continuous increasing trend in the geometric mean values of the mean corpuscular volume from 92.6 to 96.4 fL (P < 0.001) and of plasma homocysteine from 9.5 to 12.3 micromol/L (P < 0.005). The geometric mean serum alanine aminotransferase (ALT) activity slightly increased from 0.49 to 0.80 microkat/L (P < 0.05). However, only two patients had the ALT activity transiently elevated above twice the upper limit of normal. CONCLUSION: Results of this pilot trial show that the steady-state levels of MTXPGs in RBC vary less than threefold between patients and did not correlate with the change in PASI observed after 4 months of therapy with an individualised weekly dose of MTX. Whether pharmacokinetically guided dosing can improve the results of psoriasis therapy with MTX should be prospectively tested in large controlled studies.


Assuntos
Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/farmacocinética , Metotrexato/administração & dosagem , Metotrexato/farmacocinética , Psoríase/tratamento farmacológico , Administração Oral , Adulto , Idoso , Fármacos Dermatológicos/sangue , Relação Dose-Resposta a Droga , Esquema de Medicação , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Eritrócitos/metabolismo , Feminino , Humanos , Masculino , Metotrexato/sangue , Pessoa de Meia-Idade , Projetos Piloto , Psoríase/sangue , Índice de Gravidade de Doença , Resultado do Tratamento
18.
Oncogene ; 26(48): 6948-53, 2007 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-17486057

RESUMO

Cancers often exhibit high levels of cyclin E expression, and aberrant cyclin E activity causes genomic instability and increased tumorigenesis. Two tumor suppressor pathways protect cells against cyclin E deregulation. The p53 pathway is induced by excess cyclin E in primary cells and opposes cyclin E activity through induction of p21Cip1. In contrast, the Fbw7 pathway targets cyclin E for degradation, and Fbw7 mutations occur commonly in cancers. We investigated the cooperativity of these two pathways in countering cyclin E-induced genomic instability in primary human cells. We find that loss of p53 and Fbw7 synergistically unmasks cyclin E-induced instability. In normal cells, impaired cyclin E degradation produces genome instability, but this is rapidly mitigated by induction of p53 and p21. In contrast, p53 loss allows the high level of cyclin E kinase activity that results from Fbw7 loss to persist and continuously drive genome instability. Moreover, p21 plays a critical role in suppressing cyclin E when Fbw7 is disabled, and in the absence of p21, sustained cyclin E activity induces rapid cell death via apoptosis. These data directly demonstrate the cooperative roles of these Fbw7 and p53 pathways in restraining cyclin E activity and its associated genome instability.


Assuntos
Ciclina E/metabolismo , Fibroblastos/metabolismo , Proteínas Oncogênicas/metabolismo , Proteínas Ligases SKP Culina F-Box/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Apoptose , Ciclina E/genética , Fibroblastos/citologia , Instabilidade Genômica , Humanos , Immunoblotting , Imunoprecipitação , Testes para Micronúcleos , Proteínas Oncogênicas/genética , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Ligases SKP Culina F-Box/antagonistas & inibidores , Proteínas Ligases SKP Culina F-Box/genética , Proteína Supressora de Tumor p53/genética
19.
J Eukaryot Microbiol ; 53(4): 269-74, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16872294

RESUMO

During the past 16 years, the ciliate Balantidium jocularum has been collected from the intestines of many specimens of its fish host, Naso tonganus, all collected from the Great Barrier Reef near Lizard Island, Australia. Ciliates for this study of food consumption were isolated in 1988, 1989, 2003, and 2005. Nineteen specimens of B. jocularum were examined in the transmission electron microscope to determine the contents of both food vacuoles and a putative discharging cytoproct vacuole. Food vacuoles contained rod-shaped bacteria, tightly coiled spirilliform bacteria, and one or more euglenid flagellates. In several balantidia of somewhat different form than the type species of B. jocularum, the large bacterium, Epulopiscium fishelsoni, was observed in light microscope protargol preparations. Some putative phagolysosomes retained spirilliform bacteria that were apparently intact, and others contained partially digested flagellates. Food in a single discharging cytoproct vacuole consisted of normal appearing spirilliform bacteria, some other bacteria, and no flagellates. The results argue for non-selective ingestion of food and selective digestion; hence, somewhat inefficient food processing.


Assuntos
Balantidium/fisiologia , Balantidium/ultraestrutura , Intestinos/parasitologia , Perciformes/parasitologia , Vacúolos/ultraestrutura , Animais , Bactérias/ultraestrutura , Euglênidos/ultraestrutura , Microscopia Eletrônica de Transmissão , Simbiose , Vacúolos/microbiologia , Vacúolos/parasitologia
20.
J Eukaryot Microbiol ; 49(2): 146-53, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12043962

RESUMO

Four species of adult herbivorous surgeonfishes (Family Acanthuridae) were collected from the remote South-Pacific island system of Tuvalu. Their intestinal contents were examined, and of four populations of ciliated protists, two new species were discovered and are described. Ciliates were examined after protargol staining and, in some cases, scanning electron microscopy. Members of each population were examined and 10 characters measured for the balantidia, and 13 for the paracichlidotherids. A new Balantidium is described which has an unusually large dextr-oral field of cilia. A new species of Paracichlidotherus was discovered which has a macronucleus significantly smaller and well anteriad the cytoplasmic portion of the oral polykinetids relative to the type species.


Assuntos
Balantidíase/parasitologia , Balantidium/classificação , Doenças dos Peixes/parasitologia , Enteropatias Parasitárias/parasitologia , Animais , Balantidium/isolamento & purificação , Cilióforos/classificação , Cilióforos/isolamento & purificação , Enteropatias Parasitárias/veterinária , Biologia Marinha , Oceano Pacífico , Infecções por Protozoários/parasitologia
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