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Biomedical subjects

C A Gamba

Publications and source records attributed to C A Gamba.

6 recordsLinked to original sources

Nicotinamide increases thyroid radiosensitivity by stimulating nitric oxide synthase expression and the generation of organic peroxides.

Differentiated thyroid cancer and hyperthyroidism are treated with radioiodine. However, when the radioisotope dose exceeds certain limits, the patient must be hospitalized to avoid contact with people that would otherwise be exposed to radiation. It would be desirable to obtain a similar therapeutic effect using lower radioiodine doses. Radiosensitizers can be utilized for this purpose. Nicotinamide (NA) increases thyroid radiosensitivity to 131I in both normal and goitrous glands. NA causes a significant increase in thyroid blood flow, which would increase tissue oxygenation and tissue damage via free radicals. Wistar rats were treated with either nicotinamide (NA), 131I or both. The expression of the three isoforms of nitric oxide synthase (NOS) in the thyroid (Western blot) and the activities of SOD, GPx, catalase and organic peroxides were determined. Treatment with NA or 131I increased the expression of eNOS and the generation of organic peroxides. When administered jointly, they showed a synergistic effect. No changes were observed in the other NOS isoforms or in the activities of catalase, glutathione peroxidase and superoxide dismutase. NA potentiates the effect of 131I by increasing eNOS, which would in turn stimulate NO production, increasing thyroid blood flow and tissue damage via organic peroxides.

Animals↗

Changes in bone volume and bone resorption by olpadronate treatment in an experimental model of uremic bone disease.

Thirty male adult Wistar rats (300-/+10 g body weight) underwent either 5/6 nephrectomy (Nx, n=20) or sham operation (SHAM, n=10) to determine olpadronate effects in an experimental model of uremic bone disease. For a 38-day period, 10 rats received olpadronate (16microg/100g bw) once a week (Nx+OPD) and the other vehicle (Nx). SHAM received vehicle. At baseline, treatment onset (t=7 days) and end of study (t=45 days) calcium, phosphorus, creatinine, bone alkaline phosphatase (b-ALP) and deoxypyridinoline crosslinks (DPyr) were determined. At t=0 and t=45 bone mineral density (BMD) was measured by DXA. At t=45 the right tibia was removed for bone histology. There were no differences in serum calcium. Phosphorus increased in Nx and Nx+OPD compared to SHAM (p<lt 0.05). The b-ALP increased from t=0 to t=7 in Nx and Nx+OPD (p<0.05) and decreased thereafter to SHAM levels. DPyr/creat increased in Nx compared to SHAM (p<0.05) and Nx+OPD (p<0.001). Nx+OPD presented lower DPyr excretion than SHAM rats (p<0.01). At t=45, tibia BMD of Nx was 20% and 26% lower than in SHAM (p<0.005) and Nx+OPD, respectively, (p<0.001). BMD was higher Nx+OPD than in SHAM (p<0.05). OPD prevented the loss of bone volume, the increment in osteoid volume and erosion surface observed in Nx group (p<0.05). OPD also prevent the increment in the number of osteoclasts (OC) and the active OC surface and decreases the number of TRAP(+)-OC (p<0.05). In summary, OLP may be beneficial in osteopenia associated to high turnover bone disease of CRF. However, the use of bisphosphonate therapy for renal insufficiency must be further investigated in order to clarify essential aspects of treatment as the patient selection and several aspects of treatment, such as optimum dose, frequency, and safe period of administration.

Alkaline Phosphatase↗

Growth deceleration and bone metabolism in nutritional dwarfing rats.

Nutritional status as well as energy and protein intake are critical regulators of IGF-1 and IGFBP-3 and contribute to the modulation of bone remodeling and formation. The purpose of this study was to investigate on an experimental model with nutritional dwarfing (ND), whether the alterations on body growth velocity, energy metabolism and body composition could affect serum concentrations of IGF-1 and IGFBP-3 and bone (tibiae and mandible) histology and histomorphometry. Twenty-one male weanling Wistar rats (body weight = 38.20 +/- 0.94 g) were randomized to three groups: seven of them were killed at day = 0 (CO, n = 7); control (C, n = 7); and experimental 80 (E80, n = 7). During 4 weeks, C was fed ad libitum with a 1:1 carbohydrate to fat diet. E80 was being underfed with the same diet by 80% and the following parameters were measured: weight (Wt) for length (L) ratio z-score; oxygen consumption (VO2); body composition (BC) by EM-SCAN SA 3000. At t = 28, E80 and C were killed. Serum IGF-1 and IGFBP-3 and bone histology and histomorphometry were performed on C0, E80 and C. E80 showed Wt for L z-score between lean and adequate, a decrease in VO2 according to body proportions, a BC of a delayed puberty individual, IGF-1 and IGFBP-3 decreased by 56 and 53%, respectively. Tibiae's hematopoyetic and adipose bone marrow areas were combined, with sealing trabeculae on metaphyseal areas. This study suggests that there is a relationship among growth deceleration in ND rats and structural alterations on tibiae.

Animals↗

[Assessment of normal growth patterns in rats by Z score].

Malnutrition is one of the most important causes of normal growth disruption. Anthropometric methods are highly valuable in clinic pediatric diagnosis to determine the nutritional status of children and as recovery monitoring. In previous studies, we have demonstrated that the standards weight-age, height-age and weight-height of growing rats had similar distribution to those in normal children. However, to improve the diagnostic effectiveness of anthropometric information, statistical analysis to normally and non-normally distributed variables should be applied. One hundred Wistar rats (50 male and 50 female rats) from weaning (day = 25, weight = 35-40 g) to 70 days of age were fed with a commercial diet. Water and diet were offered "ad libitum". Body weight and height were recorded every two or four days, respectively. Percentiles of weight vs age, height vs age and weight vs height were plotted for male and female rats. The statistical criterion for classifying the anthropometric measurements into nutritional categories was based on percentiles cutoff and Z-score. The Z-score was calculated according to: Z = (standard mean value-subject value/standard deviation of standard). The statistical anthropometric categories of growing rats were similar to those obtained in children. This evidence suggest that the rat can be used as an experimental model to infer and predict the nutritional response in children.

Animals↗

Adrenergic receptors and secretory responses of the rat submandibular salivary gland after periodic incisor reduction.

The lower and upper incisors of female rats were repeatedly reduced every 48 hr for 21 days. A marked enlargement of the submandibular glands was observed at the end of this period. One day after the final reduction, dose dependent curves to phenylephrine and isoproterenol were obtained in relation to salivary flow rates. Secretory responses, expressed as mg/gland, showed that the dose response curve to the alpha1-adrenomimetic drug was not modified by treatment while that for isoproterenol was shifted to the right of the control. When the responses were expressed as microg of saliva/mg of wet tissue, the dose-response curve to both agonists was shifted to the right in the incisor-reduced group. (Activation of alpha2-adrenergic receptors by clonidine did not inhibit the responses to phenylephrine in the incisor-reduced rats.) Radioligand binding assays of alpha1-, beta- and alpha2-receptors did not show differences between control and experimental glands in terms of densities (Bmax) or affinities (Kd). The lack of correlation between the decrease in alpha2- and beta-mediated responses and the radioligand bindings suggests that postreceptor mechanisms are involved in the diminished secretory responses of the rat submandibular gland after periodic reduction or amputation of incisors.

Adrenergic Agonists↗

[Nutrition dwarfism: longitudinal analysis of anthropometric and metabolic parameters in rats].

UNLABELLED: Nutritional dwarfing (ND) is the result of nonorganic causes reflective of a voluntary or unintentional reduction in food intake, inappropriate eating behavior, dissatisfaction with body weight or unhealthy approaches toward weight control. Patients with ND have reached an equilibrium between their genetic growth potential and their nutritional intake. This study was undertaken to compare on a growing rat model the metabolic alterations in terms of substrate utilization (SU), oxygen consumption (VO2) and growth rate velocity. Twenty male weanling Wistar rats were randomized to 3 groups: control (C), experimental 4 (E4) and 8 (E8). C was fed "ad libitum" with a stock diet, E4 and E8 were underfed by 80% of the requirements during four or eight weeks, respectively. During the depletion phase the following measurements were performed: 1a) body weight (Wt), 1b) length, 1c) Weight for Length ratio z-score, 2) Body composition (BC) by EM-SCAN Tobec Model 3 000, Springfield. USA, 3) VO2 by indirect calorimetry, ECO-OXYMAX. RESULTS: 1) wt for length was -0.70 +/- 0.43 for E4 (t = 4 weeks) and 1.44 +/- 0.32 for E8 (t = 8 weeks), 2% of fat mass was within the normal range, 3) VO2 was not significantly different between groups. Chronic suboptimal nutrition (80%) decreased growth velocity which was the sole manifestation of nutritional inadequacy.

Animals↗