Study of the long-term carcinogenicity potential of D-003, a mixture of high molecular weight sugarcane wax acids, in mice.

D-003, a mixture of high aliphatic primary acids purified from sugar cane wax, has shown cholesterol-lowering, anti-platelet and antioxidant effects. Previous data demonstrated that D-003 was not toxic or carcinogenic when given orally to Sprague-Dawley rats up to 1500 mg/kg. This study investigated the potential long-term oral carcinogenicity of D-003 in a second rodent species. OF1 mice of both sexes were randomized into 4 groups treated for 18 months: a vehicle control group and three groups treated with D-003 at 50, 500 and 1500 mg/kg, respectively, orally gavaged 6 days per week. Mortality, clinical symptoms, weight gain, food consumption, organ weight, blood indicators and tumour incidence did not show significant differences between control and treated groups. D-003 did not increase the frequency of neoplastic or non-neoplastic lesions with respect to the controls. Lesions observed in the study were consistent with spontaneous lesions reported for this specie. It can be concluded that D-003 did not result toxic or carcinogenic when given orally to OF1 mice for 18 months and that the highest dose was a NOAEL, consistent with results of the oral carcinogenicity study of D-003 in rats.

Long-term carcinogenicity of D-003, a mixture of high molecular weight acids from sugarcane wax, in Sprague Dawley rats: a 24 months study.

D-003 is a mixture of high molecular weight sugarcane wax aliphatic primary acids with cholesterol-lowering, anti-platelet and antioxidant effects. This study investigated the long-term oral toxicity and carcinogenicity of D-003 in Sprague Dawley rats of both sexes, randomly distributed into four groups: a control group, treated only with the vehicle, and three treated with D-003 (50, 500 and 1500 mg/kg). All treatments were given orally for 24 months. Mortality (survival analysis), clinical symptoms, weight gain, food consumption, organ weights, time-to-tumour or tumour incidence data were not shown between group differences or trends. With the exception of serum cholesterol levels, lower in D-003-treated groups (500 and 1500 mg/kg) than in the controls, no other difference in blood indicators was found. D-003 did not increase the frequency of neoplastic and non-neoplastic lesions compared with the controls. The occurrence of all malignant and mammary tumours in D-003-treated females was lower than in the controls. The lesions observed were consistent with spontaneous lesions reported in this species. In conclusion, D-003 is not toxic or carcinogenic when given orally to Sprague Dawley rats up to 1500 mg/kg for 2 years, and 1500 mg/kg was a not-observable effect dose.

Perinatal/postnatal study of D-003, a mixture of long-chain fatty acids, in rats.

D-003 is a mixture of long-chain fatty acids isolated and purified from sugar cane wax with cholesterol-lowering and antiplatelet effects. In order to further characterize the developmental toxicity during the treatment period from late gestation up to weaning of the offspring, pregnant females received 0 (control), 500, and 1,000 mg/kg/day D-003 daily by oral gavage beginning at day 15 of pregnancy and through gestation until day 21 postpartum. Maternal clinical signs, body weight, and food intake were measured at regular intervals during gestation and lactation. Live pups were weighed, sexed, and examined for developmental signs. One female and male of each litter were randomly selected to evaluate the reproductive potential. There were no spontaneous or dose-related maternal deaths during the course of this study. The general health and behavioral condition of offspring was good in all groups. No significant differences among groups were found in comparisons of litter size, survival through the weaning period, sex ratio, and male and female weights. This peri- and postnatal study conducted with D-003 in rats indicated that treatment of the dam during late gestation and lactation did not show adversely effects on reproductive performance or fetal development over two generations.

[Effect of diltiazem on cold-induced left ventricular dysfunction in patients with systemic sclerosis]. / Efecto del diltiazem sobre las alteraciones cardíacas inducidas por el frío en la esclerosis sistémica.

Patients with systemic sclerosis (SS) have cardiac dysfunction induced by cold exposure. We and others have demonstrated this finding after corporal chilling, suggesting a "coronary Raynaud phenomenon" mediated by intermittent vascular spasm. In this study we evaluated the effect of diltiazem (DTZ) in cardiac dysfunction induced by cold test in patients with SS without clinical evidence of heart disease. Twelve patients with SS were studied. One patient was excluded because he did not fulfill the prescribed treatment. Eleven patients (age of 49.9 +/- 3.8 years and illness duration of 9.3 +/- 4.8 years) were included. Gated equilibrium radionuclide ventriculography was recorded after red blood cells were labeled in vivo using an intravenous injection of stannous pirophosphate followed by 20 mc of 99 Tc (gamma camera with electrocardiographic R wave gating was used). Left ventricular injection fraction (LVEF) was calculated using computer analysis and wall motion abnormalities by visual interpretation. Patients were cooled using a thermic blanket set at 5 degrees centigrade. They were evaluated before and after a period of cooling. After corporal chilling LVEF decreased more than 10% in all of them. DTZ 270 mg a day was administered to the same patients during 48 hs. Basal and cold LVEF were repeated in all patients. The results with and without DTZ were compared by Student's t Test. The basal LVEF with and without DTZ was not different (64.8 +/- 2.6 and 63.1 +/- 1.8). After corporal chilling LVEF decreased (64.8 +/- 2.6 to 54.8 +/- 2.5 p < 0.00001) and reversible abnormalities in wall motion were noticed in patients without DTZ. When they received DTZ neither difference in LVEF (63.1 +/- 1.8 to 62.1 +/- 2.4) nor wall motion abnormalities were observed. We compared the LVEF after chilling (62.1 +/- 2.4 and 54.8 +/- 2.5) and we found an important difference with the use of DTZ (p < 0.005). It can be concluded that in patients with SS and no overt heart disease, DTZ prevents the early cardiac dysfunction induced by cold test. Probably this drug blunts the coronary spasm induced by cold test in this group of patients.

[Cold-induced cardiac abnormalities in systemic sclerosis]. / Alteraciones cardíacas inducidas por el frío en la esclerosis sistémica.

Cardiac abnormalities are frequent in patients with systemic sclerosis (SS). These abnormalities have been demonstrated in over 80% of patients with SS and there are some clues that suggest that an intermittent vascular spasm (i.e. coronary Raynaud's phenomenon) is one of the causes of myocardial dysfunction in this group of patients. The aim of this prospective study was to evaluate the ventricular performance and regional wall motion during exposure to cold in patients with SS and Raynaud's phenomenon without overt cardiac disease. Twenty-four patients and 10 normal volunteers underwent radionuclide ventriculograms (RV). In each subject the RV was done thrice: basal, 20 minutes after chilling with thermic blanket and post reheating. The left ventricular ejection fraction (LVEF) decreased during the cold test (p = 0.03) with reversible abnormalities in wall motion. Basal Right Ventricular Ejection Fraction (RVEF) was lower than that of normal subjects (p = 0.02) and decreased during the cold test (p = 0.04). Therefore, we were able to demonstrate an early cardiac dysfunction associated with impaired wall motion after corporal chilling. These findings suggest that coronary spasm in SS would be an early and frequent phenomenon that would precede the development of symptomatic cardiac disease in some patients with this illness.

Alteraciones cardíacas inducidas por el frío en la esclerosis sistémica. / [Cold-induced cardiac abnormalities in systemic sclerosis]

Cardiac abnormalities are frequent in patients with systemic sclerosis (SS). These abnormalities have been demonstrated in over 80

of patients with SS and there are some clues that suggest that an intermittent vascular spasm (i.e. coronary Raynauds phenomenon) is one of the causes of myocardial dysfunction in this group of patients. The aim of this prospective study was to evaluate the ventricular performance and regional wall motion during exposure to cold in patients with SS and Raynauds phenomenon without overt cardiac disease. Twenty-four patients and 10 normal volunteers underwent radionuclide ventriculograms (RV). In each subject the RV was done thrice: basal, 20 minutes after chilling with thermic blanket and post reheating. The left ventricular ejection fraction (LVEF) decreased during the cold test (p = 0.03) with reversible abnormalities in wall motion. Basal Right Ventricular Ejection Fraction (RVEF) was lower than that of normal subjects (p = 0.02) and decreased during the cold test (p = 0.04). Therefore, we were able to demonstrate an early cardiac dysfunction associated with impaired wall motion after corporal chilling. These findings suggest that coronary spasm in SS would be an early and frequent phenomenon that would precede the development of symptomatic cardiac disease in some patients with this illness.

Effectiveness of different endodontic files for preparing curved root canals: a scanning electron microscopic study.

In this study, the effect of using four endodontic files from different manufacturers on the final shape of 80 prepared curved root canals of extracted single-rooted teeth were comparatively analyzed with scanning electron microscopy. The instruments tested were Tri-files, Flex-R files, Flexofiles and conventional K-type files. All files were used with in and out linear movements with a circumferential motion starting with a size 15 file. Final preparation of the apical thirds was performed with a size 30 file. Shaping effectiveness of the tested files was qualitatively evaluated in terms of respect for conservation of the apical constriction and the presence or absence of ledging, specially in the apical third of the root canals. A well-centered and tapered preparation without apical transportation or ledging was detected when Tri-file or Flex-R files were used. Conversely, the use of Flexofile or conventional K-type files resulted in frequent alteration of the initial pattern of the root canals, showing an hour-glass preparation with alteration of the apical constriction and ledge formations.

Método modificado para la marcación de glóbulos rojos con 99mTc / Modified method for labelling red blood cells with 99mTc

Se presenta un método simple de marcación in vivo/in vitro de glóbulos rojos con 99mTc. La sangre preestañada del paciente se incuba con el radiotrazador previo agregado de soluciones de hipoclorito de sodio y EDTA sal de sodio, según la técnica descripta por Srivastava y col. El método in vivo/in vitro fue ensayado en 18 pacientes que concurrieron para una evaluación de la fracción de eyección del ventrículo izquierdo. Se hizo un estudio comparativo con otro grupo de 11 pacientes a los cuales se aplicó el método convencional de marcación in vivo. Las imágenes obtenidas con el método in vivo/in vitro, de acuerdo con la evaluación subjetiva de 3 observadores independientes, fueron de mejor calidad y los índices de contraste presentaron menor dispersión de acuerdo al análisis estadístico (p < 0,025)

Método modificado para la marcación de glóbulos rojos con 99mTc / Modified method for labelling red blood cells with 99mTc

Se presenta un método simple de marcación in vivo/in vitro de glóbulos rojos con 99mTc. La sangre preestañada del paciente se incuba con el radiotrazador previo agregado de soluciones de hipoclorito de sodio y EDTA sal de sodio, según la técnica descripta por Srivastava y col. El método in vivo/in vitro fue ensayado en 18 pacientes que concurrieron para una evaluación de la fracción de eyección del ventrículo izquierdo. Se hizo un estudio comparativo con otro grupo de 11 pacientes a los cuales se aplicó el método convencional de marcación in vivo. Las imágenes obtenidas con el método in vivo/in vitro, de acuerdo con la evaluación subjetiva de 3 observadores independientes, fueron de mejor calidad y los índices de contraste presentaron menor dispersión de acuerdo al análisis estadístico (p < 0,025) (AU)