RESUMO
BACKGROUND: Piroxicam-beta-cyclodextrin (PBC) is the first nonsteroidal anti-inflammatory drug (NSAID), in which the active substance is complexed with the cyclic oligosaccharide cyclodextrin, which acts as an artificial receptor. This complex allows single molecules of the NSAID to be released adjacent to the gastrointestinal mucosa, instead of crystals. Since the piroxicam is immediately bioavailable in this formulation, the onset of action is similar to that of a parenteral drug. Since the time contact with gastric mucosa is reduced, the risk of direct-contact gastric irritation is also reduced. There is good evidence that PBC is beneficial in managing acute non-specific back pain (BP) but sufficient evidence on chronic BP is lacking. METHODS: Thirty-one eligible patients aged 18-85 years, resistant to previous therapy with different NSAIDs, were treated with PBC 20 mg once daily in a 40-day open-label noncomparative study. The patients experienced chronic BP defined as pain between the occipital region and gluteal fold, lasting for at least 6 weeks but not more than 6 months. Efficacy was assessed by changes in pain intensity, paravertebral tonus, functional impairment and morning stiffness using a 4-point numerical rating scale. Patients also self-assessed nocturnal and diurnal pain using the visual analogue scale. Tolerability was assessed by adverse events and routine laboratory evaluations. Global assessment of efficacy and tolerability by physician and patients was performed at the last visit. RESULTS: Using intention-to-treat analysis, all efficacy assessments demonstrated statistically significant improvements over baseline at each follow-up. 90.3% of the patients evaluated the efficacy of PBC as improved or greatly improved, and investigators rated the treatment as improved or greatly improved in 87.1% of patients. Remission was achieved in 19.3% of the patients. Tolerability was also rated highly, with 83.9% of the patients characterizing PBC treatment as good or very good, and the investigators rated the treatment as good or excellent in 87.1% of the patients. Drug related adverse events were reported in 9.7% of patients and prompted discontinuation of the study medication in 3.2% of patients. No serious adverse events were reported. CONCLUSION: These results suggest that the newly developed dosage form of piroxicam is effective and well tolerated in the treatment of patients with chronic BP. Thus, PBC, may be an important new treatment option in this condition. (Tab. 3, Fig. 3, Ref. 36.).
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Dor nas Costas/tratamento farmacológico , Ciclodextrinas/uso terapêutico , Piroxicam/uso terapêutico , beta-Ciclodextrinas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios não Esteroides/efeitos adversos , Doença Crônica , Ciclodextrinas/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piroxicam/efeitos adversosRESUMO
RATIONALE: Leptin is an adipocyte-derived hormone that declines dramatically during fasting and plays a pivotal role in the neuroendocrine response to starvation. Previously, we employed leptin-deficient (ob/ob) mice to identify an important role for leptin in the host defense against Klebsiella pneumonia. OBJECTIVES: To assess the effects of fasting on the innate immune response against pneumococcal pneumonia and to determine the effects of maintaining circulating leptin levels on host defense in fasted mice. METHODS: C57BL/6 mice were either fed ad libitum or fasted for 48 h and given an intraperitoneal injection of saline or recombinant leptin (1 microg/g of body weight) twice daily for 48 h before bacterial challenge. Mice were challenged with 10(5) cfu of Streptococcus pneumoniae via the intranasal route. MEASUREMENTS AND MAIN RESULTS: Lung homogenate S. pneumoniae burden was nearly 20-fold greater in the fasted as compared with fed mice. The impairment in bacterial clearance observed in fasted animals was associated with reduced bronchoalveolar lavage neutrophil counts and interleukin-6 and macrophage inflammatory protein-2 levels. Alveolar macrophages from fasted animals also exhibited defective phagocytosis and killing of S. pneumoniae and reduced calcium-ionophore-stimulated leukotriene B(4) synthesis in vitro. In contrast, the provision of exogenous leptin to fasted animals restored bacterial clearance, bronchoalveolar lavage levels of neutrophils and cytokines, alveolar macrophage bacterial killing, and leukotriene B(4) synthesis. CONCLUSIONS: These results suggest that reduced leptin levels substantially contribute to the suppression of pulmonary antibacterial host defense during starvation and that administration of this adipokine may be of therapeutic benefit clinically.
Assuntos
Jejum/fisiologia , Leptina/farmacologia , Pneumonia Pneumocócica/imunologia , Inanição/imunologia , Doença Aguda , Animais , Glicemia/imunologia , Peso Corporal/imunologia , Lavagem Broncoalveolar/métodos , Corticosterona/sangue , Corticosterona/imunologia , Modelos Animais de Doenças , Jejum/sangue , Interleucina-6/sangue , Interleucina-6/imunologia , Leptina/sangue , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Leucócitos/microbiologia , Leucotrieno B4/sangue , Leucotrieno B4/imunologia , Pulmão/imunologia , Pulmão/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Neutrófilos/microbiologia , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , Pneumonia Pneumocócica/sangue , Pneumonia Pneumocócica/microbiologia , Cloreto de Sódio/administração & dosagem , Inanição/sangue , Inanição/microbiologia , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/patogenicidadeRESUMO
In an epidemiologic, clinical and viral study of several influenza foci in some urban districts of Romania during January-March 1974, 23 influenza virus B Hong-Kong 8/73 strains were isolated. The dynamics of HAI serum antibodies confirmed the viral diagnosis. The epidemic ran a slow course, affecting especially the 14-25 years age group and had an evident benign clinical aspect.