Helicobacter pylori seropositivity and IL-1B C-31T polymorphism among Japanese Brazilians

We reported previously that anti-Helicobacter pylori antibody seropositivity (HP+) had an association with interleukin 1B (IL-1B) C-31T genotype, especially among smokers. This study examined the association for Japanese Brazilians. In this cross-sectional study, voluntary participation was announced through Japanese Brazilian communities in Sao Paulo, Curitiba, Mogi das Cruzes, and Mirandopolis; 963 Japanese Brazilians (399 males and 564 females) aged 33-69 years participated. Lifestyle data and peripheral blood were collected. An anti-HP IgG antibody test and genotyping for IL-1B C-31T and IL-1RN 86 bp VNTR were independently conducted. The genotype frequency of the IL-1B polymorphism among 947 individuals was 23.9% for C/C genotype, 45.6% for C/T genotype, and 30.5% for T/T genotype. Sex-age-adjusted odds ratio (aOR) of HP+ was 1.30 (95% confidence interval, 0.94-1.81) for C/T genotype and 1.45 (1.02-2.07) for T/T genotype relative to C/C genotype. The aOR for 127 current smokers was 2.45 (0.91-6.55) for C/T and 3.49 (1.17-10.46) for T/T, while that for 667 never smokers was 1.21 (0.82-1.78) and 1.36 (0.90-2.05), respectively. The corresponding figures were 2.42 (1.16-5.02) and 3.00 (1.33-6.78) for 226 current drinkers, and 1.21 (0.82-1.78) and 1.36 (0.90-2.05) for 667 non-drinkers. The difference in the OR was observed for milk consumption, salty pickled vegetable eating, and physical exercise practice. 4/4 Genotype of IL-1RN 86 bp VNTR was 84.8%, and had no association with the HP seropositivity. The observed association between HP+ and IL-1B -31TT indicated that the genetic trait also influences the susceptibility to HP for Japanese in Brazil.     

Pharmacokinetics of temocapril hydrochloride,a novel angiotensin converting enzyme inhibitor,in renal insufficiency

Summary The pharmacokinetics of temocapril hydrochloride, a novel prodrug-type angiotensin-I converting enzyme (ACE) inhibitor, has been studied in patients with mild (Group II) to severe (Group III) renal insufficiency in comparison with subjects with normal renal function (Group I).The pharmacokinetic parameters of the active diacid metabolite, including C_max, AUC and half-life (t_1/2), showed only slight changes between the three groups: AUC (0–) was significantly larger in Group III than Group I, and t1/2 tended to be prolonged in Group III, but the change was not significant.The urinary recovery of the diacid was significantly decreased in Group III. (Group I, 28.1 %, Group II, 21.6 %, Group III, 12.8 %). Compared with other ACE inhibitors, which are mainly excreted through the kidney, the plasma concentration of the active diacid metabolite was hardly influenced by renal function. It was speculated that lowering of the dose of temocapril might be recommended only in patients with severe renal insufficiency.     

Particularidades dos Pacientes com Arterite de Takayasu em Idade Mais Avançada: Estudo Coorte,Retrospectivo e Transversal

BackgroundFew studies have assessed elderly patients with Takayasu’s arteritis (TAK).ObjectivesTo evaluate the progression of TAK in different age groups and its possible effects on drug treatment and disease activity.MethodsThis cross-sectional and retrospective cohort study included 66 TAK patients. Patients were interviewed and data of the 12 preceding months were collected from electronic medical records. The patients were divided into four quartiles according to current age and compared for clinical and laboratory data, treatment, comorbidities, disease status, and functional status. Statistical significance was set at p<0.05.ResultsThe groups were Q1(22-36 years, n=16), Q2(37-42 years, n=18), Q3(43-49 years, n=17), and Q4(51-66 years, n=15). The frequency of patients with disease activity, fatigue, comorbidities and vascular impairments, and the TAK disease extent index were also comparable between the groups. With age, disease duration was longer (p=0.001), fewer patients used prednisone (Q1:43.8%, Q2:33.3%, Q3:11.8%, and Q4:6.7%; p=0.049) and immunosuppressive drugs [Q1:100.0%, Q2:66.7%, Q3:58.8%, and Q4:46.7%; Q1 versus Q3 (p=0.043), and Q1 versus Q4 (p=0.005) in post-hoc analyses], and patients had greater functional status impairment (Q2 versus Q3, p=0.003). In addition, the levels of disease damage, new TAK symptoms, and complications in the preceding 12 months were not different between the groups.ConclusionsOlder patients with TAK require minimal drug treatment, and have greater impairment of functional status, which may be attributed to aging-related factors.     

Síndrome antissintetase: anti-PL-7, anti-PL-12 e anti-EJ

ObjectivesDue to the scarcity of studies in the literature, we conducted an analysis of a series of patients with the anti-PL-7, PL-12 and EJ types of antisynthetase syndrome (ASS).MethodsWe conducted a retrospective cohort study of 20 patients with ASS (8 with anti- PL-7, 6 with PL-12, 6 with EJ) monitored in our department between 1982 and 2012.ResultsThe mean patient age at disease onset was 38.5 ± 12.9 years, and the disease duration was 4.5 ± 6.4 years. Of all the patients, 70% were white and 85% were female. Constitutional symptoms occurred in 90% of cases. All patients presented objective muscle weakness in the limbs; in addition, 30% were bedridden and 65% demonstrated high dysphagia at diagnosis. Joint and pulmonary involvement and Raynaud's phenomenon occurred in 50%, 40% and 65% of cases, respectively, with more than half of the patients presenting incipient pneumopathy, ground-glass opacity and/or pulmonary fibrosis. There were no cases of neurological and/or cardiac involvement. All patients received prednisone or other immunosuppressants depending on tolerance, side effects and/or disease refractoriness. Importantly, patients with the anti-EJ type of ASS demonstrated higher rates of recurrence. Two patients died during follow-up, and 1 patient had breast cancer at the time of diagnosis.ConclusionsASS (anti-PL-7, PL-12 and EJ) was found to predominantly affect white women. Although the autoantibodies described in the present study are more related to pulmonary than joint involvement, our patients showed a significant percentage of both types of involvement and a high percentage of myopathy. We also observed a low mortality rate.     

Development of packaging cell lines for generation of adeno-associated virus vectors by lentiviral gene transfer of trans-complementary components

Adeno-associated virus (AAV) vector system has several useful advantages with regard to in vitro and in vivo gene transfer. However, their usages have been limited by cumbersome and labor-intensive vector production in the traditional method. To overcome limitations in AAV production, in this report, we explored the possibility of generating AAV packaging cell line, 293T R/C.VA.E2A.E4. cells, by using lentivirus-mediated transduction of Rep/Cap gene of AAV-2, VA RNA, E2A, and E4 genes of Ad5 into 293T cells. In packaging cell lines, it is important that supply of the AAV vector can be stably performed for long time. We showed that the 293T R/C.VA.E2A.E4. cells have stably maintained the transduced components after more than 10 passages and yielded high-titer AAV vectors, and the titer of AAV vectors did not decline even if culture of the packaging cells was continued for long time. The Rep/Cap and E4 gene products caused no remarkable cytotoxicity. The 293T R/C.VA.E2A.E4. cells might be able to tolerate the Rep/Cap and E4 gene products, or have less copy numbers of the Rep/Cap and E4 genes than the traditional method. Moreover, we showed that the AAV vectors derived from 293T R/C.VA.E2A.E4. cells infected the primary human CD34+ haematopoietic progenitor cells with high efficiency (50-70%). In the 293T R/C.VA.E2A.E4. cells, the AAV vectors can be generated by the transfection of one AAV vector plasmid, and large-scale AAV production can be easily achieved. It is important that cumbersome, variable, and costly transfection is avoided.     

Alveolar hemorrhage: distinct features of juvenile and adult onset systemic lupus erythematosus

We compared outcomes of alveolar hemorrhage (AH) in juvenile (JSLE) and adult onset SLE (ASLE). From 263 JSLE and 1522 ASLE, the AH occurred in 13 (4.9%) and 15 (1.0%) patients, respectively (p??0.5 mg/kg/day) compared to ASLE (54% vs. 15%, p?=?.042). The mean drop of hemoglobin was significantly lower in JSLE (2.9?±?0.9 vs. 5.5?±?2.9 g/dL, p?=?.006). Although treatments with methylprednisolone, plasmapheresis, intravenous immunoglobulin and cyclophosphamide were similar in both groups (p?>?.050), regarding outcomes, there was a trend in high frequency of mechanical ventilation use (85% vs. 47%, p?=?.055) and also significant mortality (69% vs. 13%, p?=?.006) in JSLE compared to ASLE. The sepsis frequency was comparable in both groups (50% vs. 27%, p?=?.433). We have identified that AH in JSLE has a worse outcome most likely related to respiratory failure. The AH onset in JSLE already treated with high-dose steroids raises the concern of inadequate response to this treatment and reinforces the recommendation of early aggressive alternative therapies in this group of patients.