RESUMO
The differences in systemic T-cell responses between patients with psoriatic arthritis (PsA) and patients with cutaneous psoriasis (Ps) are still largely unknown. To determine differential features that could be used to distinguish PsA from Ps, we compared the cytokine secretion profile of circulating T cells in patients with PsA, patients with cutaneous Ps and control subjects. We determined Th1, Th2 and Th17 cytokine secretion of anti-CD3-stimulated peripheral blood mononuclear cells (PBMCs) using a cytokine bead array. Normality of data distribution was assessed by the Shapiro-Wilk test, and statistical significance was calculated by the Mann-Whitney test. Phenotypic characterization of circulating T cells was performed by fluorescence-activated cell sorting analysis. We found that the major systemic differences distinguishing PsA from cutaneous Ps were the increased secretion of interleukin (IL)-2 by α-CD3-stimulated PBMCs and a higher percentage of circulating CD3+ T cells expressing the proliferation marker CD71 in PsA. These results indicate IL-2 as a possible biomarker of PsA, and suggest a role of circulating T cells with high proliferative capacity in the pathogenesis of PsA.
Assuntos
Artrite Psoriásica/metabolismo , Complexo CD3/imunologia , Interleucina-2/metabolismo , Leucócitos Mononucleares/metabolismo , Psoríase/metabolismo , Adolescente , Adulto , Citocinas/metabolismo , Feminino , Citometria de Fluxo , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Linfócitos T Auxiliares-Indutores/metabolismo , Adulto JovemRESUMO
The data presented in this article are related to the research paper entitled "Observation of night-time emissions of the Earth in the near UV range from the International Space Station with the Mini-EUSO detector" (Remote Sensing of Environment, Volume 284, January 2023, 113336, https://doi.org/10.1016/j.rse.2022.113336). The data have been acquired with the Mini-EUSO detector, an UV telescope operating in the range 290-430 nm and located inside the International Space Station. The detector was launched in August 2019, and it has started operations from the nadir-facing UV-transparent window in the Russian Zvezda module in October 2019. The data presented here refer to 32 sessions acquired between 2019-11-19 and 2021-05-06. The instrument consists of a Fresnel-lens optical system and a focal surface composed of 36 multi-anode photomultiplier tubes, each with 64 channels, for a total of 2304 channels with single photon counting sensitivity. The telescope, with a square field-of-view of 44°, has a spatial resolution on the Earth surface of 6.3 km and saves triggered transient phenomena with a temporal resolution of 2.5 µs and 320 µs. The telescope also operates in continuous acquisition at a 40.96 ms scale. In this article, large-area night-time UV maps obtained processing the 40.96 ms data, taking averages over regions of some specific geographical areas (e.g., Europe, North America) and over the entire globe, are presented. Data are binned into 0.1° × 0.1° or 0.05° × 0.05° cells (depending on the scale of the map) over the Earth's surface. Raw data are made available in the form of tables (latitude, longitude, counts) and .kmz files (containing the .png images). These are - to the best of our knowledge - the highest sensitivity data in this wavelength range and can be of use to various disciplines.
RESUMO
We examined the effect of the protein kinase C-selective inhibitor AEB071 (sotrastaurin) on neutrophil functions in vitro. Pre-incubation with AEB071 at concentrations similar to those reached during in vivo therapy significantly reduced cell capacity to migrate toward three different chemo-attractants and to produce superoxide anions (O2â») in response to phorbol myristate acetate (PMA) or to N-formyl-methionyl-leucyl-phenylalanine (fMLP). AEB071 also significantly inhibited the O2â» overproduction induced by fMLP in neutrophils primed with tumor necrosis factor alpha (TNF-α) or granulocyte/macrophage-colony stimulating factor (GM-CSF). This inhibition was not linked to fMLP-receptor down-regulation since the drug had no effect on either fMLP-receptors or fMLP-induced CD11b membrane expression. When the activity of AEB071 was compared to that of the conventional protein kinase C (PKC) inhibitor Gö6850 (which, like sotrastaurin, inhibits classical and novel PKC isoforms), Gö6976 (an inhibitor of α and α PKC isoforms) and rottlerin (a prevailing δ PKC isoform inhibitor), AEB071 at an equimolar concentration of 3 µM (close to the maximum drug concentration reached in patients treated with AEB071) caused significantly more inhibition on both chemotactic response and superoxide production. These in vitro findings suggest that neutrophils may offer a cellular target for AEB071 activity in vivo.
Assuntos
Quimiotaxia de Leucócito/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Proteína Quinase C/antagonistas & inibidores , Inibidores de Proteínas Quinases/farmacologia , Pirróis/farmacologia , Quinazolinas/farmacologia , Superóxidos/metabolismo , Antígeno CD11b/metabolismo , Células Cultivadas , Relação Dose-Resposta a Droga , Fator Estimulador de Colônias de Granulócitos e Macrófagos/metabolismo , Humanos , Interleucina-1beta/metabolismo , Interleucina-8/metabolismo , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/enzimologia , Proteína Quinase C/metabolismo , Receptores de Formil Peptídeo/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Fatores de Tempo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The specific immune response against the malignant cells was investigated in patients with urinary bladder or larynx cancer. Lymphocytes from lymph nodes that drain the tumor site were tested for their proliferative and cytotoxic capacities against autologous malignant cells isolated from the primary tumor. In no occasion was a proliferative or a cytotoxic response observed. However, when the lymph node cell suspensions were depleted of cells expressing both OKM1 and Leu-7 markers by rosetting with the appropriate mAbs, a proliferative response could be observed. The lymphocytes responded to autologous tumor cells only if IL-2 was added to the cultures. IL-2 alone induced some cell proliferation, which was not, however, comparable to that observed in response to both IL-2 and tumor cells. A panel of allogeneic tumor cells consistently failed to stimulate OKM1-, Leu-7- cells in vitro. Response to autologous tumor cells was not caused by HLA-encoded molecules, as occurs in the autologous mixed lymphocyte reaction, since OKM1-, Leu-7- cells failed to be stimulated by autologous non-T cells. A proliferative response was observed only with cells from lymph nodes that had been classified as invaded by malignant cells according to histopathologic criteria. Cells from noninvaded lymph nodes consistently failed to respond. Cells stimulated with autologous tumor cells could be expanded in short-term lines by continuous addition of IL-2 and malignant cells. One of these lines, which comprised mainly T8+ cells, was stimulated to proliferate only by autologous tumor cells, and its proliferative response was inhibitable by anti-class I and not by anti-class II mAbs. This line showed lytic capacities against autologous malignant targets, while it was inefficient against all of the other allogeneic cells tested. In another set of experiments, the mechanisms whereby exogenous IL-2 had to be added to the cultures to sustain a proliferative response against neoplastic cells were investigated. When cocultured with autologous malignant cells, OKM1-, Leu-7- lymphocytes expressed IL-2 receptors, as could be assessed by anti-Tac fluorescent staining. Under these culture conditions, these cells did not produce IL-2, and no proliferation was observed. Addition of purified IL-1 to the cultures induced IL-2 production and cell proliferation. It is concluded that metastatic lymph nodes contain a T cell population that can be detected in a proliferative assay when both suppressor cells are removed and the appropriate molecular signals are supplied.
Assuntos
Interleucina-2/imunologia , Neoplasias Laríngeas/imunologia , Linfonodos/imunologia , Linfócitos T/imunologia , Neoplasias da Bexiga Urinária/imunologia , Antígenos de Superfície/análise , Citotoxicidade Imunológica , Humanos , Metástase Linfática , Ativação Linfocitária , Depleção Linfocítica , Linfócitos/imunologia , Linfócitos T Reguladores/imunologiaRESUMO
Surface-bound IgE play a central role in antiparasite immunity; to exploit IgE-driven immune mechanisms in tumor prevention and control, monoclonal IgEs of irrelevant specificity were loaded through biotin-avidin bridging onto tumor cells, either by systemic administration to tumor-bearing mice or pre-loading of tumor cells before inoculation. Here we show that systemic administration of biotinylated IgEs to mice bearing tumors pre-targeted with biotinylated antibodies and avidin significantly decreased tumor growth rate. In addition, as compared with IgG-loaded control cells, inoculation of suboptimal doses of IgE-loaded tumor cells suppressed tumor formation in a fraction of animals and induced protective host immunity by eliciting tumor-specific T-cell responses. Similarly, tumor vaccination experiments showed that irradiated tumor cells (IgE loaded by biotin-avidin bridging) conferred protective immunity at doses 100-fold lower than the corresponding control cells without IgE. Finally, in vivo depletion of eosinophils or T cells abrogated IgE-driven tumor growth inhibition. These results demonstrate that IgEs targeted on tumor cells not only possess a curative potential but also confer long-term antitumor immunity and that IgE-driven antitumor activity is not restricted to the activation of innate immunity effector mechanisms but also results from eosinophil-dependent priming of a T-cell-mediated adaptive immune response. This suggests a potential role for IgEs in the design of new cell-based tumor vaccines.
Assuntos
Anticorpos Monoclonais/farmacologia , Imunoglobulina E/imunologia , Animais , Anticorpos Monoclonais/uso terapêutico , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/imunologia , Vacinas Anticâncer/uso terapêutico , Divisão Celular/efeitos dos fármacos , Eosinófilos/citologia , Eosinófilos/efeitos dos fármacos , Eosinófilos/imunologia , Feminino , Interleucina-5/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Neoplasias Experimentais/imunologia , Neoplasias Experimentais/patologia , Neoplasias Experimentais/prevenção & controle , Análise de Sobrevida , Linfócitos T Citotóxicos/citologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Células Tumorais Cultivadas/imunologia , Células Tumorais Cultivadas/efeitos da radiaçãoRESUMO
We have shown previously that T cells, tagged with biotinylated anti-CD3 antibody fragments, can exert avidin-dependent cytolytic activity on suitably biotinylated tumor cells in vitro. In this study, we demonstrate that avidin-driven CTL-tumor bridging in vivo leads to growth inhibition of murine tumors WEHI-164 fibrosarcoma and RMA lymphoma. The biodistribution of biotin-tagged 111In-labeled T cells demonstrated a selective avidin-dependent and time-dependent accumulation of radioactivity at tumor sites. The specificity of lymphocyte tumor localization was demonstrated by the concurrent time-dependent decrease of radioactivity in the blood and in all other organs. Furthermore, we documented a therapeutic effect of the adoptively transferred T cells, i.e., a significant delay of tumor growth at early stages. All of the experiments included a control group of mice, which received all of the reagents, except avidin. These avidin-minus mice showed no specific localization and no delay in tumor growth, indicating that avidin bridging was essential for T-cell activity at tumor sites.
Assuntos
Avidina/metabolismo , Biotina/metabolismo , Imunoterapia Adotiva/métodos , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Animais , Anticorpos/imunologia , Anticorpos/metabolismo , Antígenos de Neoplasias/imunologia , Antígenos de Neoplasias/metabolismo , Biotinilação , Complexo CD3/imunologia , Citotoxicidade Imunológica , Feminino , Fibrossarcoma/imunologia , Fibrossarcoma/metabolismo , Fibrossarcoma/terapia , Linfoma de Células T/imunologia , Linfoma de Células T/metabolismo , Linfoma de Células T/terapia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Transplante de NeoplasiasRESUMO
Two new For-Met-Leu-Phe-OH (FMLP) methyl ester analogues, For-Thp-Leu-Ain-OMe [Thp1, Ain3] and For-Met-delta zLeu-Phe-OMe [delta zLeu2], able to activate selectively chemotaxis and superoxide anion (O2-) release, respectively modulate intracellular cyclic AMP (cAMP) levels in different ways. FMLP and [delta zLeu2] enhance human neutrophil cAMP levels per se, and this effect is potentiated by Ro 201724, a non-xanthinic phosphodiesterase (PDE) inhibitor, whereas it is counteracted by 3-isobutyl-1-methyl-xanthine (IBMX), a blocker of both phosphodiesterase and adenosine receptors. In contrast, [Thp1, Ain3] is ineffective. However, no formylated peptides influence cAMP phosphodiesterase activity. Neutrophil preincubation with Ro 201724 or IBMX drastically reduces chemotaxis and superoxide anion (O2-) production triggered by peptides. Our results suggest that: (1) peptide-induced cAMP increase is probably indirect, and due mainly to the action on adenosine-sensitive adenylate cyclase; (2) formylated peptide, endowed solely with chemotactic activity is unable to increase neutrophil cAMP concentration; (3) cAMP elevation may represent a feed-back mechanism to inhibit the physiological responses induced by formylated peptides.
Assuntos
Quimiotaxia de Leucócito/efeitos dos fármacos , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Explosão Respiratória/efeitos dos fármacos , 1-Metil-3-Isobutilxantina/farmacologia , 3',5'-AMP Cíclico Fosfodiesterases/metabolismo , 4-(3-Butoxi-4-metoxibenzil)-2-imidazolidinona/farmacologia , Movimento Celular , AMP Cíclico/metabolismo , Ésteres , Humanos , N-Formilmetionina Leucil-Fenilalanina/análogos & derivados , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Neutrófilos/fisiologia , Superóxidos/metabolismoRESUMO
Polymorphonuclear neutrophils (PMNs), traditionally considered effector cells in the inflammatory response, have recently been regarded as potential regulators of the immune response. In the present study we investigate whether PMNs are efficient antigen-presenting cells for reactivation of memory cytotoxic T lymphocytes (CTLs). PMNs were pulsed with synthetic peptides derived from Epstein-Barr virus (EBV) antigens. We have used the IVTDFSVIK (IVT) peptide derived from the Epstein-Barr virus-encoded nuclear antigen 4 protein, corresponding to the immunodominant epitope of HLA-AII-restricted CTL responses, and the CLGGLLTMV (CLG) peptide derived from the latent membrane protein 2 antigen, representing a subdominant epitope of HLA-A2-restricted CTL responses. The data indicate that peptide-pulsed PMNs selectively activate specific CTL responses to both immunodominant and subdominant epitopes. The efficiency of CTL induction by PMNs was comparable to that observed with the conventional method of EBV-specific CTL reactivation with the autologous lymphoblastoid cell line, as well as with peptide-pulsed monocyte-enriched adherent cells. On the contrary, unactivated peptide-pulsed lymphocytes failed to induce an epitope-specific CTL response. These results demonstrate that PMNs efficiently present antigens to memory virus-specific CTLs and suggest that they may have a role as antigen-presenting cells.
Assuntos
Antígenos Virais/farmacologia , Memória Imunológica/imunologia , Ativação Linfocitária/imunologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia , Sequência de Aminoácidos , Células Apresentadoras de Antígenos/citologia , Células Apresentadoras de Antígenos/efeitos dos fármacos , Células Apresentadoras de Antígenos/imunologia , Comunicação Celular/efeitos dos fármacos , Comunicação Celular/fisiologia , Epitopos , Imunofluorescência , Herpesvirus Humano 4/imunologia , Humanos , Memória Imunológica/efeitos dos fármacos , Dados de Sequência Molecular , Neutrófilos/citologia , Linfócitos T Citotóxicos/citologiaRESUMO
The effects of a beta interferon (beta-IFN) of human origin on different parameters of human neutrophil functioning were evaluated in vitro. In the concentration range 10(2)-10(4) IU/ml beta-IFN enhanced superoxide anion (O2-) production evoked by the peptide N-formylmethionyl-leucylphenylalanine (FMLP), 10(-7) M, when O2- production elicited by FMLP in the absence of beta-IFN treatment was 2.43 +/- 0.32 nmol cytochrome C reduced/10(6) cells/min. The enhancement afforded by 10(3) and 10(4) IU/ml beta-IFN was statistically significant. When FMLP-induced O2- generation was 4.55 +/- 0.3 nmol cytochrome C reduced/10(6) cells/min, no increase was detected after beta-IFN treatment. Phagocytosis was enhanced by beta-IFN in one case, with no effect in four others. Chemotaxis was not affected by exposure to beta-IFN. These results indicated that beta-IFN could exert modulating effects on some neutrophil functions that varied according to the extent of cell response to the stimuli.
Assuntos
Interferon Tipo I/farmacologia , Neutrófilos/efeitos dos fármacos , Quimiotaxia de Leucócito/efeitos dos fármacos , Humanos , Técnicas In Vitro , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Neutrófilos/fisiologia , Fagocitose/efeitos dos fármacos , Superóxidos/metabolismoRESUMO
Photodynamic therapy (PDT) is a treatment modality using a photosensitizer, light and oxygen to cause photochemically-induced selective cell death. Topical PDT is most suitable for thin lesions such as superficial basal cell carcinoma and actinic keratoses in dermatology. Results with PDT as treatment of thicker lesions such as nodular basal cell carcinoma appear to have a limited role because the photosensitizer or the light cannot penetrate deeply enough into the thicker tumor volume. In this preliminary study we use intralesional administration of 5-aminolevulinic acid to enhance the efficacy of the photosensitivity of nodular basal cell carcinomas, thus improving clinical cure.
Assuntos
Ácido Aminolevulínico/administração & dosagem , Carcinoma Basocelular/tratamento farmacológico , Fármacos Fotossensibilizantes/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Idoso , Carcinoma Basocelular/patologia , Feminino , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Fotoquimioterapia , Neoplasias Cutâneas/patologia , Resultado do TratamentoRESUMO
The ocular tissues can be the site of a number of malignant tumors in adults. Approximately 5% to 10% of all skin tumors occur in the eyelid. Incidence studies indicate that basal cell carcinoma is the most frequent malignant eyelid tumor (90%) followed by squamous cell carcinoma (9%). A 55-year-old man presented a squamous cell carcinoma (SCC) of 8 mm diameter, localized in the middle third of the lower eyelid, 3 mm under the eyelid margin on the eyelids. The histopathologic examination of a biopsy specimen showed the typical features of squamous cell carcinoma. Photodynamic therapy (PDT) with topical 5-aminolevulic acid (ALA) after Frost suture was employed. Very good results were obtained with rapid healing, without invasiveness, and without anesthesia. There was no evidence of scar formation and no signs of recurrence at 6 months follow-up. Many therapeutic methods have been suggested for squamous cell carcinoma of the eyelid. We consider photodynamic treatment of eyelid skin malignancies to be of great interest and it may represent an interesting future perspective for their management especially when surgical intervention cannot be tolerated by the patient.
Assuntos
Ácido Aminolevulínico/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Neoplasias Palpebrais/tratamento farmacológico , Neoplasias Palpebrais/patologia , Fotoquimioterapia/métodos , Biópsia por Agulha , Seguimentos , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Medição de Risco , Resultado do TratamentoRESUMO
The capability of potassium clavulanate to protect amoxycillin from destruction by three partially purified beta-lactamases (from E. cloacae, B. cereus 569/H9 and E. coli R-TEM) was evaluated. The enzymatic inhibition was determined spectrophotometrically by assessing the ability of either amoxycillin or potassium clavulanate or their combination (at a 7:1 ratio by weight) to prevent the hydrolysis of a chromogenic substrate (nitrocefin) after different pre-incubation times, thus determining the IC50 and Ki values. Potassium clavulanate significantly reduced the IC50 values of amoxycillin for B. cereus and TEM enzymes by a factor ranging from 500 to 1200, by inhibiting these beta-lactamases at concentrations ranging from 4 to 0.008 microM. However, clavulanic acid was quite ineffective against type I enzymes (from E. cloacae), while amoxycillin was found to be sufficiently stable (IC50 of 0.8-1.4 microM).
Assuntos
Amoxicilina/farmacologia , Ácidos Clavulânicos/farmacologia , beta-Lactamases/metabolismo , Amoxicilina/metabolismo , Bacillus cereus/enzimologia , Ácidos Clavulânicos/metabolismo , Enterobacter/enzimologia , Escherichia coli/enzimologia , Inibidores de beta-LactamasesRESUMO
A prospective multicentre study of Italian children with acute pharyngotonsillitis was carried out to determine the incidence of beta-haemolytic streptococcal infection and its epidemiological characteristics and to evaluate the effectiveness of a recently marketed macrolide, miocamycin. From February 1988 to March 1989, 865 children (aged 5 months to 14 years) were enrolled in 11 paediatric departments. Of these 31.9% had a positive throat culture for beta-haemolytic streptococci (26.6% group A streptococci, 5.3% group B, C, D or F). In 68.1% of the patients the throat culture did not yield any pathogen and the disease was considered to be probably viral. No epidemiological (age, season of occurrence, sex) or clinical characteristics (fever, pharyngeal hyperaemia, exudate etc.) could differentiate children with streptococcal pharyngotonsillitis from those with a probably viral one. Breese's score correctly identified only 19.1% of the cases with group A streptococcal infection. Miocamycin was given 50 mg/kg/day in 2 divided doses for 10 days in 225 children with streptococcal pharyngitis. The drug exhibited good clinical efficacy (resolution or improvement of acute signs and symptoms) in 96.3% of the children and a microbiological efficacy (eradication of the causative bacteria) in 85.3%.
Assuntos
Miocamicina/uso terapêutico , Faringite/tratamento farmacológico , Infecções Estreptocócicas/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Itália/epidemiologia , Masculino , Faringite/epidemiologia , Faringite/microbiologia , Estudos Prospectivos , Infecções Estreptocócicas/epidemiologiaRESUMO
Twenty-two patients with advanced prostatic cancer and one with benign prostatic hypertrophy were given the GnRH analogue leuprolide in the form of a slow-release depot formulation by subcutaneous injection at doses of 3.75, 7.5, 15 or 30 mg. Following the first dose, drug levels were measured by a double-antibody RIA over an observation period of 5 weeks. Thereafter patients continued long-term subcutaneous treatment at the same dose every 4 weeks. Serum levels of leuprolide showed a rapid increase immediately after injection, reaching a peak proportional to dose within 3 h (range of mean values 13.1-54.5 ng/ml). Subsequently, mean drug levels declined to a plateau proportional to dose (0.49-1.99 ng/ml at 5 weeks). A significant dose-dependent increase in the area under the serum concentration-time curve from zero to 35 days (AUC0-35 days) from 541.7 to 1653.9 ng/ml.h was also noted (p less than 0.01). With all doses there was an initial rise in serum LH and FSH, followed by a rise in testosterone and dihydrotestosterone, then a sharp decrease within 3 weeks. FSH inhibition was achieved in all the 20 evaluable patients and was maintained in 17 of them (85%) over 5 weeks. Fifteen subjects (75%) had marked suppression of LH levels. In 13 of them (65%) this condition continued for the entire observation time. Castration levels of serum testosterone and dihydrotestosterone, however, were maintained in all patients for up to 5 weeks. Two of the 21 evaluable patients (10%) had a complete response; 15 a partial response (71%) and 3 stable disease (14%). No significant differences were observed in relation to dose. Clinical improvement and serum hormonal changes support this as a new and superior method of administration of leuprolide at a dose as low as 3.75 mg.
Assuntos
Antineoplásicos/uso terapêutico , Hormônio Liberador de Gonadotropina/análogos & derivados , Neoplasias da Próstata/tratamento farmacológico , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Preparações de Ação Retardada , Di-Hidrotestosterona/sangue , Relação Dose-Resposta a Droga , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/farmacocinética , Hormônio Liberador de Gonadotropina/farmacologia , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Leuprolida , Hormônio Luteinizante/sangue , Masculino , Modelos Teóricos , Neoplasias da Próstata/fisiopatologia , Radioimunoensaio , Testosterona/sangueRESUMO
Teicoplanin is a recently introduced long-acting glycopeptide antibiotic effective against Gram-positive aerobic and anaerobic bacteria. The effects of hypothermic extracorporeal circulation on teicoplanin serum pharmacokinetics have been studied in 18 patients undergoing open-heart surgery for coronary artery bypass graft or prosthetic cardiac valve insertion. The patients received a single 600 mg dose of teicoplanin by intravenous (i.v.) bolus (five cases) or by i.v. infusion over 20 min (13 cases) approximately 1 h before the anticipated skin incision and 2 h before the anticipated extracorporeal circulation. Serum drug concentrations were measured by a microbiological method using Bacillus subtilis ATCC 6633 as the test organism. Following i.v. bolus injection and i.v. infusion, teicoplanin levels in serum (mean +/- s.d.) were respectively 13.9 +/- 6.8 and 11.4 +/- 2.4 mg/l at the beginning of extracorporeal circulation, 8.8 +/- 3.5 and 10.2 +/- 2.3 mg/l at the end of this procedure and 2.8 +/- 0.6 and 2.9 +/- 1.0 mg/l at 24 h after surgery. Mean AUCs were 378.1 +/- 52.5 and 328.9 +/- 88.0/l.h and mean elimination half-life values were 27.9 +/- 12.7 and 30.3 +/- 11.0 h, respectively under the same conditions. These differences in plasma pharmacokinetic parameters were not significant. Teicoplanin pharmacokinetics in patients undergoing cardiopulmonary bypass surgery were similar to those observed in non-surgical patients with normal renal and hepatic function, confirming experimental evidence for lack of effects of extracorporeal circulation.
Assuntos
Ponte Cardiopulmonar , Pré-Medicação , Infecções Bacterianas/prevenção & controle , Feminino , Glicopeptídeos/sangue , Glicopeptídeos/farmacocinética , Glicopeptídeos/uso terapêutico , Próteses Valvulares Cardíacas , Humanos , Infusões Intravenosas , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , TeicoplaninaRESUMO
The pharmacokinetic properties were investigated of teicoplanin, including its penetration into suction blister fluid (SBF), after a single intravenous bolus administration of 600 mg in seven pneumological patients with normal renal and hepatic function. Blood and SBF samples were collected during the 60-hour period drug administration. Teicoplanin was assayed microbiologically and the mean serum concentration at the end of the i.v. injection was 98.7 +/- 16 mg/l falling to 2.3 +/- 0.4 mg/l at 60 h. The antibiotic was rapidly distributed into a fast equilibrating peripheral compartment and, at a lower rate, into a slowly equilibrating peripheral compartment, while the mean elimination half-life (t1/2 beta) was 34.1 +/- 6.8 h. Penetration into the SBF, though slow, was good, reaching a mean peak level of 8.7 +/- 1.7 mg/l at a mean time of 2.1 h, with a penetration index (obtained by percentage ratio of the area under curve in the SBF to that of serum) of 42.9%.
Assuntos
Antibacterianos/farmacocinética , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/sangue , Vesícula/metabolismo , Líquidos Corporais/metabolismo , Feminino , Glicopeptídeos/administração & dosagem , Glicopeptídeos/sangue , Glicopeptídeos/farmacocinética , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , TeicoplaninaRESUMO
In this multicentre study we evaluated the prevalence and risk factors of otitis media with effusion (OME) in Italian school-children and the effectiveness of medical treatment of chronic OME with a new cephalosporin, ceftibuten. During two winter periods, 3413 children, aged 5 to 7 years, were examined for the presence of OME by means of pneumotoscopy and a portable, hand-held tympanometer. The prevalence of asymptomatic OME was 14.2%, with no difference as regards sex, age, month of examination or geographic area. Younger children had significantly more bilateral than unilateral effusion. A recent episode of acute otitis media and previous tonsillectomy or adenoidectomy were associated with an increased risk of OME in multivariate logistic regression models. The presence of OME was unrelated to such factors as birthweight, prematurity, sibling or parental history of allergy, duration of daycare attendance, family history of ear infections. After 12 weeks, 26.6% of children with OME still had middle-ear fluid: 52 were randomized to ceftibuten (9 mg/kg q.d. for 14 days) and 59 to no treatment (nasal saline drops allowed). Children treated with ceftibuten had a significantly better resolution of middle-ear effusion after 4 and 8 weeks. As mass screening programmes for OME in the year of school entry are questioned, a focus only on children with known risk factors seems advisable. Ceftibuten can be useful in reducing the duration of middle-ear effusion.
Assuntos
Cefalosporinas/uso terapêutico , Otite Média com Derrame/tratamento farmacológico , Otite Média com Derrame/epidemiologia , Ceftibuteno , Criança , Pré-Escolar , Feminino , Humanos , Itália/epidemiologia , Modelos Logísticos , Masculino , Prevalência , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
In this work we present preliminary results of nuclear composition measurements on board space station MIR obtained with SILEYE-2 particle telescope. SILEYE-2 was placed on MIR in 1997 and has been working since then. It consists of an array of 6 active silicon strip detectors which allow nuclear and energetic identification of cosmic rays in the energy range between approximately 30 and 200 MeV/n. The device is attached to an helmet and connected to an eye mask which shields the cosmonaut eyes from light and allow studies of the Light Flashes (LF) phenomenon. In addition to the study of the causes of LF, the device is used to perform real time long term radiation environment monitoring inside the MIR, performing measurements in solar quiet and active days.
Assuntos
Radiação Cósmica , Fosfenos , Monitoramento de Radiação/instrumentação , Atividade Solar , Voo Espacial/instrumentação , Relação Dose-Resposta à Radiação , Desenho de Equipamento , Meio Ambiente Extraterreno , Olho/efeitos da radiação , Dispositivos de Proteção da Cabeça , Humanos , Luz , Estimulação Luminosa , Silício , Astronave/instrumentaçãoRESUMO
The SilEye experiment aims to study the cause and processes related to the anomalous Light Flashes (LF) perceived by astronauts in orbit and their relation with Cosmic Rays. These observations will be also useful in the study of the long duration manned space flight environment. Two PC-driven silicon detector telescopes have been built and placed aboard Space Station MIR. SilEye-1 was launched in 1995 and provided particles track and LF information; the data gathered indicate a linear dependence of FLF(Hz) ( 4 2) 10(3) 5.3 1.7 10(4) Fpart(Hz) if South Atlantic Anomaly fluxes are not included. Even though higher statistic is required, this is an indication that heavy ion interactions with the eye are the main LF cause. To improve quality and quantity of measurements, a second apparatus, SilEye-2, was placed on MIR in 1997, and started work from August 1998. This instrument provides energetic information, which allows nuclear identification in selected energy ranges; we present preliminary measurements of the radiation field inside MIR performed with SilEye-2 detector in June 1998.
Assuntos
Radiação Cósmica , Luz , Prótons , Voo Espacial/instrumentação , Percepção Visual/efeitos da radiação , Adaptação à Escuridão , Interpretação Estatística de Dados , Humanos , Estimulação Luminosa , Doses de Radiação , Silício , Astronave/instrumentaçãoRESUMO
The ALTEA project participates to the quest for increasing the safety of manned space flights. It addresses the problems related to possible functional damage to neural cells and circuits due to particle radiation in space environment. Specifically it aims at studying the functionality of the astronauts' Central Nervous Systems (CNS) during long space flights and relating it to the peculiar environments in space, with a particular focus on the particle flux impinging in the head. The project is a large international and multidisciplinary collaboration. Competences in particle physics, neurophysiology, psychophysiology, electronics, space environment, data analyses will work together to construct the fully integrated vision electrophysiology and particle analyser system which is the core device of the project: an helmet-shaped multi-sensor device that will measure concurrently the dynamics of the functional status of the visual system and passage of each particle through the brain within a pre-determined energy window. ALTEA is scheduled to fly in the International Space Station in late 2002. One part of the multi-sensor device, one of the advanced silicon telescopes, will be launched in the ISS in early 2002 and serve as test for the final device and as discriminating dosimeter for the particle fluences within the ISS.