RESUMO
The prevention and treatment of type-2 diabetes mellitus (T2DM) and diabetic nephropathy (DN), which are disorders with high incidence rates, is of primary importance. In this study, we analyzed the effect of 1,25-(OH)2D3 and lipopolysaccharide (LPS) in combination with interleukin (IL)-15 on the inflammatory immune response and expression of vitamin D receptor (VDR) in mononuclear cells of T2DM and DN uremia (DNU) patients. The human acute monocytic leukemia cell line THP-1 was treated with peripheral blood serum isolated from 30 healthy controls and T2DM and DNU patients each, cultured in the presence or absence of 1,25-(OH)2D3, and subsequently treated with LPS and IL-15. The VDR mRNA and protein expression in THP-1 cells was detected by real-time polymerase chain reaction and western blot (and immunofluorescence assay), respectively, and IL-6 and IL-10 concentrations in the culture supernatant were detected by enzyme-linked immunosorbent assay. LPS treatment induced a significant decrease in VDR mRNA expression in T2DM and DNU serum-treated THP-1 cells compared to the control cells (P < 0.05). The VDR protein expression in DNU serum-treated THP-1 cells was also significantly down-regulated (P < 0.05). LPS treatment induced IL-6 secretion in serum-treated THP-1 cells (P < 0.05), while 1,25-(OH)2D3 treatment inhibited IL-6 secretion to some extent. These findings suggested that LPS down-regulates the expression of VDR in mononuclear cells of T2DM and DNU patients and induces an imbalance in the pro-inflammatory and anti-inflammatory cytokine response, while 1,25-(OH)2D3 partially reversed the effect of LPS and protected patients with T2DM and DNU.
Assuntos
Calcitriol/farmacologia , Diabetes Mellitus Tipo 2/imunologia , Nefropatias Diabéticas/imunologia , Monócitos/efeitos dos fármacos , Receptores de Calcitriol/genética , Uremia/imunologia , Estudos de Casos e Controles , Linhagem Celular , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/patologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/patologia , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Soros Imunes/farmacologia , Interleucina-10/biossíntese , Interleucina-10/imunologia , Interleucina-15/antagonistas & inibidores , Interleucina-15/farmacologia , Interleucina-6/biossíntese , Interleucina-6/imunologia , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Masculino , Monócitos/citologia , Monócitos/imunologia , Receptores de Calcitriol/agonistas , Receptores de Calcitriol/antagonistas & inibidores , Receptores de Calcitriol/imunologia , Uremia/sangue , Uremia/patologiaRESUMO
Entre as classes terapêuticas analisadas no Programa Nacional de Verificação da Qualidade de Medicamentos (PROVEME), o antifúngico fluconazol constava na apresentação de cápsulas de diferentes procedências. Na realização dos ensaios de dissolução conforme as técnicas dos fabricantes, constatou-se que os valores obtidos por espectrofotometria-UV foram superiores aos obtidos nos ensaios de teor e uniformidade de conteúdo, cuja determinação foi por CLAE-UV. Considerando este fato, foi objetivo deste trabalho realizar o ensaio de dissolução destas amostras pelos respectivos métodos dos fabricantes e o quantitativo do ensaio por espectrofotometria no UV e por CLAE-UV, a fim de avaliar as possíveis interferências dos excipientes nestas determinações. Os valores obtidos por espectrofotometria foram superiores aos obtidos por CLAE, confirmando a interferência dos excipientes. Concluiu-se que a metodologia a ser empregada na análise de fármacos deve ser criteriosamente selecionada, a fim de evitar resultados não condizentes com a real formulação do produto.
Among the therapeutic classes analyzed in the Programa Nacional de Verificação da Qualidade de Medicamentos (PROVEME) consisted the antifungal fluconazole in the dosage form of capsules from different origins. In dissolution tests, according to manufacturers techniques, it was found that the values obtained by UV-spectrophotometry were higher than those obtained from tests of content and content uniformity, whose determination was by HPLC-UV. Considering this fact, the objective of this study was to perform the dissolution test of these samples by the respective manufacturers methods and the quantitative assay by UV-spectrophotometry and HPLC-UV, to evaluate possible interferences of excipients in these determinations. The values obtained by spectrophotometry were higher than those obtained by HPLC, confirming the excipients interference. It was concluded that the methodology to be employed in drug analysis should be carefully selected in order to avoid results not commensurate with the real product formulation.
Assuntos
Humanos , Dissolução , Fluconazol , Cápsulas , EspectrofotometriaRESUMO
There are treatments to induce the long term suppression of viral replication and that delays the progression of HIV disease. To be effective, these treatments require the uninterrupted use of a combination of drugs (ideally three), patients must be highly compliant, must be instituted in early stages of the disease and drugs must be used for prolonged periods and given by specialists. These treatments are indicated in all symptomatic patients and in those with early immunologic deterioration or high viral load. Recent infection and acute primary retroviral infections should also be considered for treatment. The treatment sponsored and financed by the ministry of health for its beneficiaries is insufficient at this time, since it is received by a minority of eligible patients due to budgetary reasons, and only two drugs are given which is considered such optimal by most experts. The committee considers that the responsibility for financing, providing and delivering these treatments in proper combination and dosages exceeds the duty of the Ministry of Health and should include all the involved parties. However, the state and its official institutions have a special responsibility to provide with adequate treatments to the poorer segments of our population. They also should promote, supervise and control the proper access of the rest of the population to efficient treatments. The committee also considers that the efforts to prevent new infections must not be neglected and that individuals under successful treatment should not consider themselves as non infectious.
Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Síndrome da Imunodeficiência Adquirida/virologia , Chile , HIV/fisiologia , Infecções por HIV/prevenção & controle , Humanos , Replicação ViralRESUMO
AIM: To study the epidemiology of invasive pneumococcal infections in infants and young children in Santiago, Chile, as a representative pediatric population in a newly industrializing country where pneumococcal conjugate vaccines may be used in the future. METHODS: A 5-year retrospective laboratory-based review (1989 to 1993) was followed by a 3-year prospective laboratory and hospital surveillance study in two of the six health administrative areas of Santiago to detect all hospitalized cases of invasive pneumococcal disease (defined as Streptococcus pneumoniae isolated from blood, cerebrospinal fluid or another normally sterile site) among infants and children (0 to 23 months of age in the retrospective and 0 to 59 months of age in the prospective study). RESULTS: During the 5-year retrospective survey the incidence of invasive pneumococcal disease was 90.6 cases per 10(5) infants 0 to 11 months old and 18.5 cases per 10(5) toddlers 12 to 23 months old. Similar rates (60.2 per 10(5) infants and 18.1 per 10(5) toddlers) were recorded during the 3 years of prospective surveillance. Among the 110 cases in children 0 to 59 months of age detected during the 3-year prospective surveillance, 2 clinical forms, pneumonia and meningitis, accounted for 87.2% of all cases; 13 of the 49 pneumonia patients (26%) had empyema as a complication. Notably 40 of the 110 cases (36.4%) occurred before 6 months of age (63.4% of the 63 infant cases). Serotypes 1, 14, 5 and 6B were the most prevalent. Overall 76 and 69%, respectively, of S. pneumoniae isolates were antigenic types that would be covered by the 11- or 9-valent conjugate vaccines under development. CONCLUSIONS: Invasive pneumococcal infections in Santiago, Chile, exhibit an epidemiologic pattern intermediate between that of developing and industrialized countries. The high burden of disease in early infancy dictates that an accelerated immunization schedule (beginning in the perinatal period) or maternal immunization with pneumococcal vaccines should be explored.
Assuntos
Infecções Pneumocócicas/epidemiologia , Streptococcus pneumoniae/classificação , Fatores Etários , Pré-Escolar , Chile/epidemiologia , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Meningite Pneumocócica/epidemiologia , Meningite Pneumocócica/microbiologia , Infecções Pneumocócicas/microbiologia , Pneumonia Pneumocócica/epidemiologia , Pneumonia Pneumocócica/microbiologia , Vigilância da População , Estudos Prospectivos , Estudos Retrospectivos , Sorotipagem , Streptococcus pneumoniae/isolamento & purificação , População UrbanaRESUMO
P carinii is an opportunistic pathogenic agent able to produce severe infection that must be diagnosed promptly. We analyzed 138 samples from 100 patients suspected of having infection by P carinii. The ortho-toluidine blue and the methenamine stains were used to analyze the samples. Infection was demonstrated in 18 patients, 13 adults and 5 children. Underlying disease was AIDS in 7 and other immunosuppressive disorders in the rest. No immunocompetent patient was infected with P carinii. Proper sample collection is important for diagnosis. When bronchoalveolar lavage is not possible, pharyngo-tracheal aspirate in children and sputum sampling after assisted coughing in adults are recommended. At least 2 staining methods and proper controls are advisable.
Assuntos
Pneumonia por Pneumocystis/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/complicaçõesRESUMO
Five cases of probably intrauterine herpesvirus infection are discussed. Four of them had clinical evidence of neonatal herpes, which was disseminated in two patients, localized to skin in one case and with SNC compromised in other. Natal or post natal infections were not considered to be possible in these infants due to the presence of symptoms in the first 24 hours of life, which made ascending transcervical or transplacental the most probable route for viral transmission. All cases were treated with a ten days course of intravenous acyclovir during 10 days. There of them had satisfactory evolution and the other two died at 9 days and at 2 months of life.
Assuntos
Infecções por Herpesviridae/congênito , Complicações Infecciosas na Gravidez , Aciclovir/uso terapêutico , Adolescente , Adulto , Feminino , Infecções por Herpesviridae/diagnóstico , Infecções por Herpesviridae/tratamento farmacológico , Humanos , Recém-Nascido , Masculino , GravidezRESUMO
Sixteen fatal cases of adenovirus infection in infants (n:10 aged 1 to less than 12 months) and children (n:6 aged 1 to 3, 8/12 years) are reported. Diagnosis were confirmed by direct viral isolation, viral immunofluorescence or both in 15 patients, and by autopsy in 12 of them, including one without positive virological workup. Evidence of multisystemic compromise, particularly that of severe lower respiratory tract infection was observed and lead to death by acute respiratory failure in all cases. White blood cell counts and erythrocyte sedimentation rate did not help to label initially the etiology as either viral or bacterial. Chest roentgenograms showed pulmonary over-inflation and evidence of pneumonitis as well as extensive and rapidly progressive lung opacifications. Most prominent pathologic findings were necrotizing bronchitis, bronchiolitis and broncopneumonia. Several cells containing typical intranuclear inclusion bodies were documented in ten cases and pneumonitis was the only finding in two. Hepatic fat infiltration and lymphocitic depletion of thymus, spleen and lymphatic nodes occurred in all cases. The need of rapid diagnostic tools to avoid nosocomial spread of this kind of infections with such serious consequences is stressed.
Assuntos
Infecções por Adenovirus Humanos/complicações , Infecções Respiratórias/etiologia , Adenovírus Humanos/isolamento & purificação , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Infecções Respiratórias/tratamento farmacológico , Infecções Respiratórias/mortalidade , Infecções Respiratórias/patologiaRESUMO
To study the incidence of nosocomial respiratory tract infection along the first week after admission, 31 children under 2 years of age admitted to the pediatric wards of a general hospital at Metropolitan Santiago, Chile, with the diagnosis of lower respiratory tract infection, were studied for viral agents by immunofluorescence tests, viral isolation from pharyngeal aspirates, paired serum viral antibodies and bacterial cultures, all of them performed at admission and 4 to 5 days later from May through August 1988. In 13 out of 31 patients admitted because of acute lower respiratory tract infection at least one new virus (to a total of 18 viral isolates) was detected in the second sample, which could have been nosocomially acquired, as follows: adenovirus from 8 cases, respiratory syncytial virus from 5 patients and cytomegalovirus from 5 patients, in different combinations. No significant changes in bacterial cultures were found.