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1.
J Antimicrob Chemother ; 72(7): 1981-1984, 2017 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-28369424

RESUMO

Objectives and methods: We evaluated the in vitro activity of different antimicrobial combinations with and without colistin against 39 carbapenem-resistant Klebsiella pneumoniae (CR-Kp) strains (colistin + meropenem/doripenem, colistin + tigecycline, colistin + rifampicin, gentamicin + meropenem, gentamicin + tigecycline and the double-carbapenem regimen meropenem + ertapenem) using the chequerboard method. The triple combination colistin + meropenem + tigecycline was also tested. In addition, killing studies were performed for meropenem + ertapenem. Results: Gentamicin-based combinations showed a high level of synergy. Meropenem + ertapenem was synergic in 12/39 (30.7%) of the strains, whereas based on killing studies 1 × MIC meropenem + 1 × MIC ertapenem and 2 × MIC meropenem + 1 × MIC ertapenem combinations were bactericidal and synergic at 24 h [mean area under the bactericidal curve (AUBC) 54.9 ±âŸ26.1 and 44.2 ±âŸ15.3 compared with 1 × MIC meropenem (134.5 ±âŸ40.1) and 2 × MIC meropenem (126.4 ±âŸ5.4), respectively, P < 0.0001]. When the results were stratified according to meropenem MIC, we found that the degree of synergy significantly increased for isolates with lower meropenem (and not ertapenem) MICs, up to an MIC of 128 mg/L. Among colistin-containing combinations, synergy was observed in 18/39 (46.1%), 33/34 (97%), 24/39 (61.5%) and 17/39 (43.5%) of the strains for colistin + meropenem, colistin + rifampicin, colistin + tigecycline and colistin + doripenem, respectively, including colistin-resistant strains. Colistin + meropenem + tigecycline at subinhibitory concentrations resulted in the absence of growth of 37/39 strains (94.8%). Conclusions: Our in vitro data suggest that colistin might be a valid therapeutic option against CR-Kp, even in the presence of colistin resistance, whereas the double-carbapenem regimen represents a viable option when colistin is not recommended, especially if the meropenem MIC is ≤ 128 mg/L. Since traditional antimicrobial susceptibility reports are not sufficiently informative for clinicians, synergy testing as well as actual meropenem MIC evaluation should always be performed in the case of CR-Kp infections.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/biossíntese , Carbapenêmicos/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Tienamicinas/farmacologia , beta-Lactamases/biossíntese , Enterobacteriáceas Resistentes a Carbapenêmicos , Colistina/farmacologia , Doripenem , Farmacorresistência Bacteriana Múltipla , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/enzimologia , Meropeném , Testes de Sensibilidade Microbiana
2.
Phys Chem Chem Phys ; 18(36): 25528-25537, 2016 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-27711611

RESUMO

Mixtures of metal salts such as ZnCl2, AlCl3 and CrCl3·6H2O form eutectic mixtures with complexing agents, such as urea. The aim of this research was to see if alkali metal salts also formed eutectics in the same way. It is shown that only a limited number of sodium salts form homogeneous liquids at ambient temperatures and then only with glycerol. None of these mixtures showed eutectic behaviour but the liquids showed the physical properties similar to the group of mixtures classified as deep eutectic solvents. This study focussed on four sodium salts: NaBr, NaOAc, NaOAc·3H2O and Na2B4O7·10H2O. The ionic conductivity and viscosity of these salts with glycerol were studied, and it was found that unlike previous studies of quaternary ammonium salts with glycerol, where the salt decreased the viscosity, most of the sodium salts increased the viscosity. This suggests that sodium salts have a structure making effect on glycerol. This phenomenon is probably due to the high charge density of Na+, which coordinates to the glycerol. 1H and 23Na NMR diffusion and relaxation methods have been used to understand the molecular dynamics in the glycerol-salt mixtures, and probe the effect of water on some of these systems. The results reveal a complex dynamic behaviour of the different species within these liquids. Generally, the translational dynamics of the 1H species, probed by means of PFG NMR diffusion coefficients, is in line with the viscosity of these liquids. However, 1H and 23Na T1 relaxation measurements suggest that the Na-containing species also play a crucial role in the structure of the liquids.

3.
J Biol Regul Homeost Agents ; 28(1): 105-16, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24750796

RESUMO

Morphine and related opioid drugs are currently the major drugs for severe pain. Their clinical utility is limited in the management of severe cancer pain due to the rapid development of tolerance. Restoring opioid efficacy is therefore of great clinical importance. A great body of evidence suggests the key role of free radicals and posttranslational modulation in the development of tolerance to the analgesic activity of morphine. Epidemiological studies have shown a relationship between the Mediterranean diet and a reduced incidence of pathologies such as coronary heart disease and cancer. A central hallmark of this diet is the high consumption of virgin olive oil as the main source of fat which contains antioxidant components in the non-saponifiable fraction, including phenolic compounds absent in seed oils. Here, we show that in a rodent model of opiate tolerance, removal of the free radicals with phenolic compounds of olive oil such as hydroxytyrosol and oleuropein reinstates the analgesic action of morphine. Chronic injection of morphine in mice led to the development of tolerance and this was associated with increased nitrotyrosin and malondialdehyde (MDA) formation together with nitration and deactivation of MnSOD in the spinal cord. Removal of free radicals by hydroxytyrosol and oleuropein blocked morphine tolerance by inhibiting nitration and MDA formation and replacing the MnSOD activity. The phenolic fraction of virgin olive oil exerts antioxidant activities in vivo and free radicals generation occurring during chronic morphine administration play a crucial role in the development of opioid tolerance. Our data suggest novel therapeutic approach in the management of chronic cancer pain, in particular for those patients who require long-term opioid treatment for pain relief without development of tolerance.


Assuntos
Analgésicos Opioides/farmacologia , Antioxidantes/uso terapêutico , Morfina/farmacologia , Neoplasias/fisiopatologia , Olea/química , Dor Intratável/tratamento farmacológico , Álcool Feniletílico/análogos & derivados , Piranos/uso terapêutico , Animais , Tolerância a Medicamentos , Glucosídeos Iridoides , Iridoides , Peroxidação de Lipídeos , Masculino , Camundongos , Estresse Oxidativo , Álcool Feniletílico/uso terapêutico , Superóxido Dismutase/metabolismo
4.
Musculoskelet Surg ; 108(3): 275-288, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38829480

RESUMO

Intra-articular injection-based therapy is often used aside conservative treatment and lifestyle modifications to manage knee osteoarthritis (KO) patients. Conventional injections contain steroids and hyaluronic acid, while more recently multipotential adult stem cell, platelet-rich plasma (PRP), and platelet lysate (PL) injections have been used to promote cartilage regeneration or repair. The aim of the current study is to analyse current evidence on PL injections for the treatment of KO and to determine if these are effective and how these perform compared to other injection regimens. The databases of Scopus, Embase, PubMed, Web of Science, and Cochrane Library were searched on 30 June 2023. Risk of bias was assessed using the SYRCLE tool for animal studies and Cochrane RoB 2 as well as ROBINS-I tool for human studies. Studies were included if these were in English, any year, and regarded animals with osteoarthritis (OA) or human adult patients with OA. In vitro trials and non-adult human studies were excluded. Results on OA symptom stage and severity, and pain were recorded. The research retrieved three human studies (n = 48, n = 25, n = 58) and four animal studies: one rabbit, two studies, and one rat study. PL was found to decrease KO symptoms at follow-up ≤ 1 year with respect to baseline levels and when compared to hyaluronic acid or platelet-rich plasma. Symptoms returned 6 months-1 year after the final administration, with studies showing peak efficacy at approximately 6 months. Animal studies showed clinical improvements, reduction of lameness, and partial effect on the cartilage regeneration of the seven studies, two had a high risk of bias, four were associated to some concerns, and one had low risk. A major source of bias in these studies was the use of questionnaires and scoring that could be subject to interpretation. Overall, PL was well-tolerated and showed efficacy comparable to PRP; when pain control was assessed, it showed similar efficacy compared to hyaluronic acid. These findings may support its use in clinical trials to confirm these initial findings; future research should also focus on the comparison with other non-surgical treatments, on a more detail of the potential regenerative properties, and to optimise the treatment schedule.


Assuntos
Plaquetas , Osteoartrite do Joelho , Animais , Humanos , Coelhos , Ratos , Modelos Animais de Doenças , Injeções Intra-Articulares , Osteoartrite do Joelho/terapia , Plasma Rico em Plaquetas , Resultado do Tratamento
5.
Am J Transplant ; 13(3): 802-7, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23331771

RESUMO

We report the case of a 68-year-old woman who underwent heart transplantation for hypertrophic cardiomyopathy. Two months after the transplant she developed mild fever and dyspnea with a marked drop in left ventricle ejection fraction of 31%. Coronary angiography was negative for cardiac allograft vasculopathy. Endomyocardial biopsy revealed ischemic damage with no evidence of acute cellular rejection, antibody-mediated rejection or viral myocarditis. A neoplastic process was suspected even though full-body computerized tomography was negative for malignancy. The patient died 4 months after transplantation. The autopsy showed acute antero-septal myocardial infarction due to a nodular epicardial EBV-related posttransplant lymphoproliferative disorder (PTLD) infiltrating the left anterior descending coronary artery with occlusive neoplastic thrombosis. We highlight two major aspects of this case: (1) the unusual occurrence of early PTLD involving the cardiac allograft and causing a fatal outcome, (2) the application of an immunological technique for HLA-DRB1 typing to posttransplant paraffin-embedded autopsy material to identify the recipient origin of this early malignancy, thus excluding a possible donor-transmitted neoplasm.


Assuntos
Cardiomiopatia Hipertrófica/cirurgia , Rejeição de Enxerto/diagnóstico , Cadeias HLA-DRB1/genética , Transplante de Coração/efeitos adversos , Transtornos Linfoproliferativos/diagnóstico , Complicações Pós-Operatórias , Idoso , Cardiomiopatia Hipertrófica/complicações , Cardiomiopatia Hipertrófica/virologia , DNA Viral/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/virologia , Evolução Fatal , Feminino , Rejeição de Enxerto/etiologia , Herpesvirus Humano 4/isolamento & purificação , Teste de Histocompatibilidade , Humanos , Transtornos Linfoproliferativos/etiologia , Análise de Sequência com Séries de Oligonucleotídeos
6.
Neuropathol Appl Neurobiol ; 39(7): 750-61, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23452232

RESUMO

AIMS: Sporadic inclusion-body myositis (s-IBM) is an age-associated degenerative muscle disease. Characteristic features are muscle-fibre vacuolization and intramuscle-fibre accumulations of multiprotein aggregates, which may result from the demonstrated impairments of the 26S proteasome and autophagy. Chaperone-mediated autophagy (CMA) is a selective form of lysosomal degradation targeting proteins carrying the KFERQ motif. Lysosome-associated membrane protein type 2A (LAMP2A) and the heat-shock cognate protein 70 (Hsc70) constitute specific CMA components. Neither CMA components nor CMA activity has been studied in normal or disease human muscle, to our knowledge. METHODS: We studied CMA components by immunocytochemistry, immunoblots, real-time PCR and immunoprecipitation in: (a) 16 s-IBM, nine aged-matched normal and nine disease control muscle biopsies; and (b) cultured human muscle fibres (CHMFs) with experimentally inhibited activities of either the 26S proteasome or autophagy. RESULTS: Compared with age-matched controls, in s-IBM muscle, LAMP2A and Hsc70 were on a given transverse section accumulated as aggregates in approximately 5% of muscle fibres, where they (a) colocalized with each other and α-synuclein (α-syn), a CMA-targeted protein; and (b) were bound to each other and to α-syn by immunoprecipitation. By immunoblots, LAMP2A was increased sevenfold P < 0.001 and Hsc70 2.6-fold P < 0.05. LAMP2A mRNA was increased 4.4-fold P < 0.001 and Hsc70 mRNA 1.9-fold P < 0.05. In CHMFs inhibition of either the 26S proteasome or autophagy induced CMA, evidenced by a significant increase of both LAMP2A and Hsc70. CONCLUSIONS: Our study demonstrates, for the first time, up-regulation of CMA components in s-IBM muscle, and it provides further evidence that altered protein degradation is likely an important pathogenic aspect in s-IBM.


Assuntos
Autofagia/fisiologia , Proteínas de Membrana/metabolismo , Chaperonas Moleculares/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Miosite de Corpos de Inclusão/metabolismo , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Lisossomos/metabolismo , Masculino , Pessoa de Meia-Idade , Fibras Musculares Esqueléticas/patologia , Miosite de Corpos de Inclusão/patologia , Complexo de Endopeptidases do Proteassoma/metabolismo , RNA Mensageiro/metabolismo , Regulação para Cima/fisiologia , alfa-Sinucleína/metabolismo
7.
Musculoskelet Surg ; 107(1): 19-28, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36630067

RESUMO

Templating plays a key role in surgery that is often underestimated. There is a difference between planning and templating: in the first not only the hip is considered but involves the evaluation of the patient in its entirety. Templating instead consists of calculating the position of the implant in order to place it in the best possible position. Fundamental is a correct X-ray of the pelvis, which must follow certain standards. For traditional templating, drawings on appropriately enlarged transparent implants were provided by the prosthesis manufacturer. The implementation of digital software into clinical practice has improved the accuracy and reproducibility of templating, which in most surgical units is performed by standard 2D radiographic images. Thanks to digital preoperative templating in a digital radiology environment, the hip reconstructive surgeon can perform preoperative planning and implant sizing quickly, consistently, and affordably. Currently, 3D templating can also be performed by software used initially to create personalized stems for THA. Aim of the current review is to outline the essentials of correct templating in THA performance, and to report the updates since the introduction of digital and 3D technologies in this setting.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Humanos , Artroplastia de Quadril/métodos , Reprodutibilidade dos Testes , Cuidados Pré-Operatórios/métodos , Radiografia , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/cirurgia , Estudos Retrospectivos
8.
Musculoskelet Surg ; 107(4): 431-437, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37314642

RESUMO

INTRODUCTION: Total hip arthroplasty (THA) is a successful surgery, but despite the advancements in anesthesiology and orthopedics, sometimes blood transfusions are required to manage the anemia due to the blood loss, involving a substantial number of patients. The aim of this retrospective comparative study is to define how the choice of the surgical approach, either direct anterior (DA) or posterolateral (PL), may influence the postoperative blood loss and the need for transfusion in THA. MATERIALS AND METHODS: Data collection was carried out retrospectively of THAs performed between 2016 and 2021 on primary hip osteoarthritis treated by DA or with PL approach. Clinical and perioperative anesthetic data were collected. Preoperative hemoglobin levels were compared with the lowest detected level by calculating ΔHb (hemoglobin decrease). Then, data from the two groups were cross-checked: duration of surgery, whether premedication with tranexamic acid, duration of the hospitalization, rate of need for hemotransfusions, and amount of blood transfused. The two samples were subdivided into subgroups according to age, BMI, tranexamic acid prophylaxis, and chronic treatment with drugs that alter coagulative properties. RESULTS: Time of surgery was longer for patients treated with DA access (mean DA: 78.8 min; mean PL: 74.8 min; p: 0.05; 95% CI), but the length of hospitalization was shorter for patients treated with DA group with a mean time of 6.23 days versus 7.12 days for the PL group (p < 0.01). DA THA resulted advantageous mainly in patients between 66 and 75 years, showing a reduced postoperative transfusion requirement in the postoperative period (DA: 13.43%-mean: 1.33 units; PL: 26.82%-mean: 1.18 units; p: 0.044, 95% CI). Patients that assume blood-altering drugs showed a higher transfusion rate (p < 0.01), but comparison of the two subgroups showed that the choice of the surgical approach did not significantly affect the transfusion rate in these patients (p: 0.512). Prophylaxis with tranexamic acid reduced the transfusion rate (p < 0.01). CONCLUSION: Patients treated by minimally invasive direct anterior approach undergo a significantly shorter hospitalization. From the analysis of patient's subgroups those aged between 66- and 75-years benefit from the DA approach mainly for the minor blood loss with less frequent transfusion requirement.


Assuntos
Artroplastia de Quadril , Ácido Tranexâmico , Humanos , Idoso , Artroplastia de Quadril/métodos , Ácido Tranexâmico/uso terapêutico , Estudos Retrospectivos , Perda Sanguínea Cirúrgica/prevenção & controle , Hemoglobinas
9.
Nat Med ; 6(7): 762-8, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10888924

RESUMO

Mycophenolic acid, a selective inhibitor of the de novo synthesis of guanosine nucleotides in T and B lymphocytes, has been proposed to inhibit human immunodeficiency virus (HIV) replication in vitro by depleting the substrate (guanosine nucleotides) for reverse transcriptase. Here we show that mycophenolic acid induced apoptosis and cell death in a large proportion of activated CD4+ T cells, thus indicating that it may inhibit HIV infection in vitro by both virological mechanisms and immunological mechanisms (depletion of the pool of activated CD4+ T lymphocytes). Administration of mycophenolate mophetil, the ester derivate of mycophenolic acid, to HIV-infected subjects treated with anti-retroviral therapy and with undetectable viremia resulted in the reduction of the number of dividing CD4 + and CD8+ T cells and in the inhibition of virus isolation from purified CD4+ T-cell populations. Based on these results, the potential use of mycophenolate mophetil in the treatment of HIV infection deserves further investigation in controlled clinical trials.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Apoptose , Infecções por HIV/tratamento farmacológico , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Linfócitos T/efeitos dos fármacos , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Imunossupressores/farmacologia , Imunossupressores/uso terapêutico , Ativação Linfocitária/efeitos dos fármacos , Ácido Micofenólico/farmacologia
10.
Infection ; 38(2): 102-7, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20191397

RESUMO

BACKGROUND: The aim of this paper was to enlarge the available knowledge on clinical and etiological aspects of patients affected by spondylodiscitis. PATIENTS AND METHODS: All patients with spondylodiscitis admitted between January 2001 and December 2007 at the 1,300-bed University Hospital "Policlinico Umberto I" of Rome, Italy, were followed. Demographic characteristics, underlying diseases, invasive procedures, imaging studies, isolated microorganisms, treatment, complications, and outcome were recorded. RESULTS: Eighty-one patients of mean age 57.7 +/- 14.7 years with lumbosacral (72.8%), thoracic (14.8%), and cervical tract (12.3%) site of infection were included, of which 38 developed community-acquired (CA) spondylodiscitis and 43 developed hospital-acquired (HA) spondylodiscitis. Underlying disease was present in 49.4% of patients. HA spondylodiscitis was diagnosed earlier (46.8 +/- 49.7 days) than CA spondylodiscitis (65.0 +/- 55.4 days) (P < 0.05). The most frequently isolated microorganisms were Staphylococcus aureus (28 strains, 43.1%), coagulase-negative staphylococci (CNS) (eight strains, 12.3%), Pseudomonas aeruginosa (eight strains, 12.3%), and three methicillin-resistant S. aureus (MRSA) strains were isolated in CA spondylodiscitis. Fungi and yeasts, isolated in six patients, represented 9.2% of all strains but 17.6% when considering only HA spondylodiscitis. Over 85% of patients were managed by conservative treatment alone, and the treatment time depended on clinical and laboratory evidence. Poor outcome was recorded in 12 (14.8%) patients, and was associated with neurological deficit symptoms (relative risk [RR] 2.87; 95% confidence interval [CI] 1.02-8.07; P < 0.05) and the time between diagnosis and the onset of symptoms > or = 60 days (RR 2.65; 95% CI 0.92-7.59; P < 0.05). CONCLUSIONS: Infectious spondylodiscitis affects most frequently the elderly population, who are more exposed to healthcare contacts. Consequently, the infection etiology includes a growing proportion of multi-resistant bacteria and fungi.


Assuntos
Bactérias/isolamento & purificação , Infecções Bacterianas/epidemiologia , Discite/epidemiologia , Discite/microbiologia , Fungos/isolamento & purificação , Micoses/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Animais , Bactérias/classificação , Infecções Bacterianas/microbiologia , Infecções Bacterianas/patologia , Discite/patologia , Feminino , Fungos/classificação , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/microbiologia , Micoses/patologia , Estudos Prospectivos , Fatores de Risco , Cidade de Roma/epidemiologia , Adulto Jovem
13.
Artigo em Inglês | MEDLINE | ID: mdl-27459146

RESUMO

OBJECTIVE: Second-trimester uterine rupture is a rare disorder and it is unclear if it should be managed with caesarean section, repair or hysterectomy. This article provides a case report of second-trimester uterine rupture repair, and reviews the risk factors, signs and symptoms, suturing technique and newborn outcome. METHODS: PubMed was searched using the terms 'uterine rupture', 'second trimester' and 'repair' Only cases of second-trimester uterine rupture repair that led to successful prolongation of pregnancy were included. RESULTS: The main risk factor of uterine rupture is previous caesarean section (5/10, 50%). Eight of 10 cases presented with abdominal pain and three cases presented in shock. Haemoperitoneum was present in five cases. The mean and median gestational age at delivery were 33.4 and 33.5 weeks, respectively (range 28-37 weeks), with mean and median delayed interval delivery of 95.5 and 91 days, respectively (range 14-147 days). Neonatal outcome was good for 10 of 11 newborns. Despite the early onset of uterine rupture, there were no cases of extremely preterm delivery. One early preterm infant, seven moderate-to-late preterm infants and one term infant were delivered. CONCLUSIONS: The lack of extremely preterm deliveries and good neonatal outcomes encourage attempts to repair the uterus after second-trimester rupture.


Assuntos
Complicações na Gravidez/cirurgia , Ruptura Uterina/cirurgia , Adulto , Feminino , Humanos , Gravidez , Resultado da Gravidez , Segundo Trimestre da Gravidez , Resultado do Tratamento
14.
Clin Microbiol Infect ; 22(2): 147-153, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26409059

RESUMO

Available therapeutic options against carbapenem-resistant Klebsiella pneumoniae (CR-Kp) are limited because of the high level of resistance to other antimicrobial classes including polymyxins. The double-carbapenem regimen has been recently considered a possible therapeutic strategy. In the present study, we evaluated the in vitro bactericidal and synergistic activity of a double-carbapenem regimen consisting of ertapenem plus high-dose meropenem in a series of patients with healthcare-associated CR-Kp infections in whom the use of colistin was not indicated because of potential nephrotoxicity and/or resistance. In vitro synergy was evaluated using checkerboard and killing studies. A total of 15 patients were included in the study, with sepsis, severe sepsis and septic shock found in two (13.3%), five (33.3%) and one (6.7%) patients, respectively. Overall, the clinical/microbiological response was 12/15 (80%). Synergy was observed in 11/14 (78.6%) isolates using the checkerboard method whereas in killing studies 12/14 (85.7%) and 14/14 (100%) strains were synergistic and bactericidal at 24 h at concentrations of 1 × MIC MEM+1 × MIC ERT and 2 × MEM+1 × MIC ERT, respectively, with a significant decrease of log CFU/mL compared with other combinations (p <0.0001). The double-carbapenem regimen showed clinical and in vitro effectiveness in patients with CR-Kp infections.


Assuntos
Antibacterianos/administração & dosagem , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Sepse/tratamento farmacológico , Tienamicinas/administração & dosagem , beta-Lactamas/administração & dosagem , Idoso , Antibacterianos/farmacocinética , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Relação Dose-Resposta a Droga , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Sinergismo Farmacológico , Ertapenem , Feminino , Humanos , Infecções por Klebsiella/complicações , Infecções por Klebsiella/microbiologia , Masculino , Meropeném , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Sepse/microbiologia , Tienamicinas/farmacologia , beta-Lactamas/farmacologia
15.
AIDS ; 13(8): 883-90, 1999 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-10371168

RESUMO

OBJECTIVE: To investigate the effect of highly active antiretroviral treatment (HAART) on neutrophil and monocyte function in patients with moderately advanced HIV-1 infection. DESIGN: Eighteen HIV-1-infected patients with CD4 T cell counts below 350/microl, no concomitant active infection, and no previous use of protease inhibitors were treated with indinavir or ritonavir and two reverse-transcriptase inhibitors and were followed up for 9 months. Ten age- and sex-matched healthy subjects were included as controls. METHODS: The functional activity of neutrophils and monocytes was measured by assessing chemotaxis towards a bacterial peptide, killing activity against Candida albicans, and oxidative burst as measured by chemiluminescence production. RESULTS: Neutrophils and monocytes from the treatment group exhibited a significantly diminished baseline chemotactic and fungicidal activity compared with healthy controls (P < 0.001). After starting HAART, there was a significant improvement in chemotaxis and fungicidal activity of phagocytic cells (P < 0.001). Values of chemotaxis reached normal ranges in 13 out of 18 patients (72%) for neutrophils and eight out of 18 (44%) for monocytes, whereas phagocyte killing was rarely restored to normal values (3/18 cases for monocytes and 0/18 for neutrophils). The administration of HAART was also associated with significantly increased phagocyte chemiluminescence production in response to phorbol-12-myristate 13-acetate or opsonized C. albicans (P < 0.01). CONCLUSION: The functional improvement of two critical components of innate antimicrobial immunity, such as neutrophils and monocytes, may contribute to the improved cell-mediated immune responses against opportunistic infections in HAART-treated patients.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1 , Monócitos/imunologia , Neutrófilos/imunologia , Adulto , Idoso , Candida albicans/imunologia , Quimiotaxia de Leucócito , Quimioterapia Combinada , Feminino , Infecções por HIV/imunologia , Inibidores da Protease de HIV/uso terapêutico , Humanos , Medições Luminescentes , Masculino , Pessoa de Meia-Idade , Fagocitose , Estudos Prospectivos , Explosão Respiratória , Inibidores da Transcriptase Reversa/uso terapêutico
16.
Am J Psychiatry ; 140(5): 609-11, 1983 May.
Artigo em Inglês | MEDLINE | ID: mdl-6846593

RESUMO

Sixteen depressed patients underwent 1- and 2-mg overnight dexamethasone suppression tests in balanced order. Serum cortisol concentrations at all time points were significantly higher after the 1-mg dose. Nine patients were nonsuppressors after the 1-mg dose, and 4 after the 2-mg dose.


Assuntos
Transtorno Depressivo/diagnóstico , Dexametasona , Hidrocortisona/sangue , Adulto , Idoso , Transtorno Depressivo/sangue , Dexametasona/administração & dosagem , Relação Dose-Resposta a Droga , Humanos , Masculino , Pessoa de Meia-Idade
17.
HIV Clin Trials ; 2(2): 108-12, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11590518

RESUMO

UNLABELLED: Interleukin (IL)-7 is a critical cytokine regulating T-lymphocyte development, regeneration, and function. PURPOSE: This study analyzes the endogenous IL-7 production in HIV-infected patients receiving highly active antiretroviral treatment (HAART). METHOD: Plasma levels of IL-7 were measured by enzyme-linked immunosorbent assay (ELISA) in 11 patients with untreated advanced HIV disease, in 8 patients who successfully responded to HAART, and in 9 individuals with virological and immunological treatment failure. RESULTS: We found that in the patients with advanced HIV disease and no treatment IL-7 concentrations were elevated and were inversely related to both CD4 + and CD8 + T-cell counts. When IL-7 was assessed in treated patients, this cytokine was below the detection limit of the assay in all participants who responded to HAART. On the contrary, patients with evidence of HAART failure had increased concentrations of IL-7 that were comparable to those found in the untreated group with progressive disease. CONCLUSION: These data suggest that IL-7 may play a role in the immune reconstitution of T-cells during HIV infection, especially in the context of potent antiretroviral treatments.


Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Interleucina-7/sangue , Adulto , Contagem de Linfócito CD4 , Linfócitos T CD8-Positivos , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/fisiologia , Humanos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue
18.
FEMS Immunol Med Microbiol ; 21(1): 11-7, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9657316

RESUMO

Monocytes/macrophages from human immunodeficiency virus (HIV)-infected patients had a defect in their ability to kill Rhodococeus equi in vitro, as compared with healthy HIV-seronegative individuals. Virulent and avirulent R. equi strains isolated from humans and horses showed no significant intracellular replicative differences within both HIV-positive and -negative monocytes/macrophages. Infection with R. equi induced the production of nitric oxide (NO) by monocytes/macrophages from healthy individuals, but not by cells from HIV-positive patients. The NO formation was significantly inhibited by L-NG-monomethyl arginine and arginase. However. neither competitive inhibition of NO synthesis from L-arginine with L-NMMA nor depletion of arginine with arginase altered the killing activity of human monocytes/macrophages against R. equi, thus suggesting that L-arginine:NO pathway is not required for the intracellular antirhodococcal mechanisms of human monocytes/macrophages.


Assuntos
Citotoxicidade Imunológica/fisiologia , Infecções por HIV/imunologia , Macrófagos/imunologia , Monócitos/imunologia , Óxido Nítrico/metabolismo , Rhodococcus equi/imunologia , Infecções Oportunistas Relacionadas com a AIDS/imunologia , Infecções por Actinomycetales/imunologia , Animais , Arginase/farmacologia , Células Cultivadas , Citotoxicidade Imunológica/efeitos dos fármacos , Cavalos , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/microbiologia , Monócitos/metabolismo , Monócitos/microbiologia , Óxido Nítrico Sintase/antagonistas & inibidores , Nitritos/metabolismo , Rhodococcus equi/efeitos dos fármacos , Rhodococcus equi/fisiologia , ômega-N-Metilarginina/farmacologia
19.
Eur J Clin Nutr ; 54(2): 155-8, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10694787

RESUMO

OBJECTIVE: The aim of this study was to evaluate the effects of an oligoantigenic and histamine-free diet on patients affected with chronic idiopathic urticaria (CIU). DESIGN: Ten patients with chronic idiopathic urticaria were prescribed an oligoantigenic and histamine-free diet for 21 days, followed by serial and controlled reintroduction of foods during a further 70 days. Modification in clinical illness as well as histamine plasma levels, post-heparin plasma diamine oxidase (DAO) and intestinal permeability were evaluated. RESULTS: The oligoantigenic and histamine-free diet induced a significant improvement of symptoms (P<0.05). Moreover, CIU patients on free diet showed higher histamine plasma levels (P<0. 05 vs post-diet and vs controls) that fell to control levels during the oligoantigenic and histamine-free diet. Post-heparin plasma diamine oxidase values were slightly reduced and were unchanged during the diet as well as intestinal permeability, which was always normal in all patients. CONCLUSIONS: These data suggest that histamine plays a major role in chronic idiopathic urticaria. The finding of normal intestinal permeability suggests that a morphological damage of intestinal mucosa should be excluded in these patients. However, the presence of low levels of post-heparin plasma diamine oxidase may indicate a subclinical impairment of small bowel enterocyte function that could induce a higher sensitivity to histamine-rich or histamine-producing food. European Journal of Clinical Nutrition (2000) 54, 155-158


Assuntos
Dieta , Histamina/administração & dosagem , Histamina/sangue , Urticária/dietoterapia , Adulto , Amina Oxidase (contendo Cobre)/sangue , Antígenos/administração & dosagem , Doença Crônica , Feminino , Hipersensibilidade Alimentar/imunologia , Humanos , Absorção Intestinal , Masculino , Pessoa de Meia-Idade , Indução de Remissão
20.
J Infect ; 35(1): 83-4, 1997 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9279732

RESUMO

A case of an Italian AIDS patient who developed both meningitis and cerebral mass lesion as a final relapse of disseminated histoplasmosis is reported. Central nervous system (CNS) involvement occurred while the patient was receiving both amphotericin B and itraconazole as maintenance therapy, thus indicating the difficulty of eradicating histoplasmosis in patients with AIDS.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Histoplasma , Histoplasmose/induzido quimicamente , Meningite/microbiologia , Infecções Oportunistas Relacionadas com a AIDS/líquido cefalorraquidiano , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Adulto , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Evolução Fatal , Histoplasmose/líquido cefalorraquidiano , Histoplasmose/tratamento farmacológico , Humanos , Itália , Itraconazol/uso terapêutico , Masculino , Meningite/tratamento farmacológico
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