Farmacocinética e farmacodinâmica de derivado ftalimídico planejado para o tratamento da anemia falciforme

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Graft versus host disease in a rat small bowel transplant model after T-cell depleted donor specific bone marrow infusion

Baixas doses de irradiação associadas à infusão de células da medula óssea não previnem a ocorrência da reação do enxerto versus hospedeiro após o transplante intestinal. OBJETIVO: Neste estudo foi avaliado a potencial vantagem em estender o regime imunossupressor associado a infusão de células de medula óssea do doador depletadas de células T na prevenção da reação do enxerto versus hospedeiro após o transplante intestinal. MÉTODOS: Transplante heterotópico de intestino delgado foi realizado em ratos Lewis como receptores e da como doadores, distribuídos em cinco grupos de acordo com a duração da imunossupressão, irradiação e do uso de medula óssea normal ou depletada: G1 (n=6), sem irradiação e G2 (n=9), G3 (n=4), G4 (n=5) e G5 (n=6) foram irradiados com 250 rd. Grupos1, 2, 4 e G3 e 5 foram infundidos com 100 x 10(6) células da medula normal e depletada respectivamente. Animais no G1,2,3 foram imunossuprimidos com 1mg/kg/FK506/ IM por cinco dias e G4 e cinco por 15 dias. Anticorpos monoclonais contra células CD3 e colunas magnéticas foram utilizadas para a depleção da medula óssea. Os animais foram examinados para a presença de rejeição, reação do enxerto versus hospedeiro, chimerismo e biópsias intestinais e da pele. RESULTADOS: Rejeição mínima foi observada em todos os grupos; entretanto, a reação do enxerto versus hospedeiro somente nos animais irradiados. Extensão da imunossupressão alterou a gravidade da reação nos animais dos G4 e 5. Rejeição foi a causa mortis no G1 e a reação do enxerto versus hospedeiro nos Grupos 2,3,4 e 5, não controlada com a infusão de medula óssea depletada. O chimerismo total e de células T do doador foi estatisticamente maior nos grupos irradiados em comparação ao G1. CONCLUSÃO: A extensão do regime de imunossupressão associado a baixas doses de irradiação diminui a gravidade da reação do enxerto versus hospedeiro, não abolida pelo uso de medula óssea depletada.

Blink reflex in end-stage-renal disease patients undergoing hemodialysis

This study analyses the blink reflex in 20 adult male patients with terminal chronic renal failure undergoing hemodialysis. Abnormalities were found in ten patients (50%), eight of them with conduction studies showing axonal peripheral neuropathy. Dialysis time was longer for patients with blink reflex alterations (median 55.1 months) than for patients with normal blink reflex (median 36.3 months). Different types of early R1 and late R2 component abnormalities were recorded. The late response abnormalities may indicate subclinical functional or anatomical impairment of the low brainstem reticular formation in patients with chronic renal failure. (C) 2002 Elsevier B.V. Ltd. All rights reserved.

The influence of loss of bone mass on induced periodontal disease: A radiographic and densitometric study of female rats

Background: Changes in mineral density in the mandibular and femoral bones (BMD) after estrogen deficiency caused by ovariectomy (OVX) and the influence of these changes on induced periodontal disease were evaluated in female rats.Methods: Forty-eight female Holtzman rats (90 days old) were randomly divided into five groups: 0: control (N = 9); 1: SHAM without induced periodontal disease (N = 11); 2: SHAM with induced disease (N = 10); 3: OVX without induced disease (N = 9); and 4: OVX with induced disease (N = 9). In groups 2 and 4, the first lower molars were tied with ligatures for 30 days 120 days after surgery. After 5 months the animals were sacrificed to measure global mineral density (BMD) and that of the sub-regions of the mandible and femur by dual energy x-ray absorptiometry (DXA). The extent of vertical bone loss was evaluated with digital radiography by measuring the distance from the bone crest to the cemento-enamel junction at the mesial of the first lower molar.Results: Results of the femur (Kruskal-Wallis test) showed a significant difference (P < 0.001) between the groups SHAM and OVX in bone density values for all regions. Comparison between the groups in relation to the BMD of the mandible, both in the sub-regions and global revealed no differences (P < 0.05). The vertical bone loss measured for the groups with induced disease was similar (P= 0.713).Conclusions: Differences between the groups were found in the bone mineral density BMD of the femur but not of the mandible. OVX had no influence on induced periodontal disease.

The use of bone scintigraphy to detect active Hansen's disease in mutilated patients

Mutilation of extremities was very frequent in patients affected by leprosy in the past; although it is now much less common, it is still seen, mainly in patients with long-term disease. In general, mutilation of the nose and ears is caused by the bacillus and mutilation of the hands and feet a consequence of chronic trauma. Leprosy must be chronically treated and any decision to interrupt therapy is based on laboratory tests and biopsy. Scintigraphy is a non-invasive procedure which could be of great value in to determining disease activity. We studied eight patients (five males and three females, aged 64-73 years) who presented with mutilation of the nose (2), ear (1), feet (3) or foot and hand (2), Conventional three-phase bone scintigraphy (750 MBq) and X-ray examinations of the affected areas were performed in all patients. Bone scintigraphy was abnormal in four patients (the presence of bacilli was confirmed by biopsy in two of them), and normal in the other four. In all patients except for the one with ear mutilation, radiography only showed the absence of bone. We conclude that bone scintigraphy is very useful to determine disease activity in cases of mutilation caused by leprosy. It seems to be superior to conventional radiography and may enable bone biopsies to be avoided.

Periodontal disease characterization in dogs with normal renal function or chronic renal failure

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of the period after ovariectomy on femoral and mandibular bone density and on induced periodontal disease

Background: This study investigated the influence of the period after ovariectomy on femoral and mandibular bone mineral density (BMD) and on induced periodontal disease.Methods: One hundred and twenty-six female Holtzman rats were divided into nine groups: control, sham surgery (SHAM) with and without induction of periodontal disease for 51 and 150 days, and ovariectomy (OVX) with and without induction of periodontal disease for 51 and 150 days. Periodontal disease was induced by placing ligatures on the first lower molars during the last 30 days of each period. BMD was measured by dual-energy x-ray absorptiometry. Vertical bone loss was determined by measuring the distance from the alveolar bone crest to the cemento-enamel junction on the mesial side of the first lower molar.Results: Statistical analyses (Kruskal-Wallis test) revealed a significant difference between the OVX and SHAM groups' global and femoral proximal epiphysis BMD (P < 0.001) for 150 days and in the global evaluation for 51 days. For mandibular BMD, no difference was found between the groups of each period. Influence of the period on femoral BMD was found only for the SHAM groups, with lower BMD for the 51-day period compared to the 150-day period (P < 0.05). In the global evaluation of the mandible, a lower BMD was found after 51 days. The period was a contributing factor for the vertical bone loss, and it resulted in higher values for the 51-day period (P < 0.05).Conclusion: the period influenced the femoral BMD and the vertical bone loss in induced periodontal disease.

Frequency of coronary artery disease in patients with renal artery stenosis without clinical manifestations of coronary insufficiency

Atherosclerotic renal artery stenosis (RAS) and coronary artery disease (CAD) arise from the same multiple risk factors. The purpose of this study was to assess the frequency of previously undiagnosed CAD in patients with angiographically confirmed RAS, by conducting coronary arteriography in the same setting. of 57 consecutive patients referred for renal arteriography on clinical grounds during a 14-month period, 28 had no RAS and 6 had RAS, but previously documented CAD. of the remainder 23 patients. 17 (74%; CI 56%-92%) had both RAS and CAD (7 single vessel, 4 two-vessel, and 7 multivessel disease). The clinical characteristics, such as age, blood pressure (BP) levels, signs of heart failure, were no different between those with and without CAD, although the 4 diabetic patients, the 4 patients with fundoscopic findings of grade III retinopathy, 11 of 14 with peripheral arterial disease, and 7 of 8 patients with prior stroke belonged in the CAD group. None developed complications as a result of the two consecutive procedures. The data suggest that in patients with RAS the frequency of silent CAD is high and cannot be predicted on clinical grounds alone, therefore coronary angiography should be routinely recommended in the same setting.

Effect of induced diabetes mellitus on alveolar bone loss after 30 days of ligature-induced periodontal disease

Several studies have shown that diabetics are more susceptible to the development of severe periodontal disease. Currently, the use of animal models can be considered a feasible alternative in radiographic assessments of these two pathologies. The purpose of this radiographic study was to evaluate the effect of induced diabetes mellitus on alveolar bone loss after 30 days of ligature-induced periodontal disease. Sixty-four Wistar rats were randomly distributed into four experimental groups. Diabetes was induced in Groups II and IV, while periodontal disease was induced in Groups III and IV; Group I was used as control. In order to perform the radiographic assessment of the specimens, the rats were killed on the 3rd and 30th days of the study. Radiographic measurements were assessed with ANOVA and Tukey's test to determine statistically significant differences (p < 0.05). It was observed that Groups III and IV featured greater bone loss when compared to Groups I and II. Only the diabetic group with periodontal disease (Group IV) featured statistically significant greater bone loss when compared to the other groups. These results suggested that the alveolar bone loss resulting from the periodontal disease installation is greater when associated to the diabetes mellitus.