Search PubMed⌕ Search

Biomedical subjects

F Santos

Publications and source records attributed to F Santos.

At least 55 records · Page 3Linked to original sources

Severe experimental uraemia does not decrease the population of rat pituitary somatotrophs.

BACKGROUND: Growth hormone (GH) secretion by the anterior pituitary has been shown to be depressed in severely uraemic rats. Changes in the population of pituitary somatotrophs might be partially responsible for this decrease. METHODS: To analyse the population of pituitary somatotrophs in severe uraemia, immunocytochemical detection and quantification of GH-producing cells were carried out on paraffin sections from young rats either 5/6 nephrectomized, sham-operated fed ad libitum or sham-operated pair-fed with the nephrectomized animals. RESULTS: Nephrectomized rats were severely uraemic and growth retarded. The overall cell density (total pituitary cells/mm2) was higher in 5/6 nephrectomized animals in comparison with the two sham-operated groups. Thus, although the percentage of GH cells was slightly lower in nephrectomized than in control rats, no difference in either the density (cells/mm2) or the cross-sectional area of GH cells was found among groups. CONCLUSIONS: These results suggest that severe experimental uraemia interferes with the maturation process of the pituitary gland and support the contention that differences in either the number or the size of pituitary somatotrophs cannot explain the reduced GH secretion previously reported in severely uraemic rats.

Animals↗

Left ventricular remodeling in myocardial hibernation.

BACKGROUND: Left ventricular (LV) remodeling as a consequence of extensive myocardial infarction has been well established in animal and human studies. This study was designed to determine whether regional LV dysfunction with myocardial hibernation without transmural or extensive infarction could initiate the remodeling process. METHODS AND RESULTS: A severe left anterior descending coronary artery stenosis was created to reduce resting flow by approximately 40% (from 0.99+/-0.10 to 0.56+/-0.11 mL x min(-1) x g[-1]) and was maintained for 7 days in 13 pigs. The reduction of regional coronary flow initially produced acute myocardial ischemia, as evidenced by reduced regional wall thickening, from 37+/-3% at baseline to 9+/-7%, regional lactate production and a decrease in regional coronary venous pH. All pigs had significant regional LV dysfunction and reduced LV ejection fraction (41+/-11%). The LV end-diastolic volume increased from 59+/-9 mL at baseline to 74+/-13 mL immediately after placement of the stenosis and to 78+/-17 mL 7 days later with hibernating myocardium. The LV mass did not change immediately (60+/-8 g baseline versus 59+/-11 g immediately after creation of the stenosis) but increased modestly yet significantly to 67+/-15 g after 7 days of myocardial hibernation subtending the severe LAD stenosis. The reductions of coronary flow and wall thickening were unchanged at 7 days, whereas myocardial lactate production recovered. By 4 weeks after restoration of LAD flow, regional function had recovered in all 7 pigs with follow-up. Of the 13 pigs, 6 were free from any evidence of myocardial infarction, and 4 had patchy necrosis involving less than 6% of the area at risk. CONCLUSIONS: LV remodeling, which is commonly associated with extensive myocardial infarction, can be initiated by regional dysfunctional hibernating myocardium resulting from a severe coronary stenosis. Myocardial necrosis is not a prerequisite for LV remodeling in response to regional dysfunction.

Animals↗

Impaired secretion of growth hormone in experimental uremia: relevance of caloric deficiency.

To evaluate the impact of uremia and associated caloric restriction on physiologically pulsatile growth hormone (GH) release, we used deconvolution analysis of spontaneous plasma GH profiles in 5/6-nephrectomized male rats (NX, N = 9). Three different normal renal function sham-operated groups were used: rats fed a normal diet ad libitum (SAL, N = 9); NX pair-fed rats (SPF, N = 6); NX rats pair-fed for protein ingestion but calorically supplemented up to the energy intake of SAL (SPF+, N = 8). Severe renal failure was confirmed by much higher (P < 0.001) BUN in NX than sham groups. NX rats were growth retarded as shown by reduced (P < 0.01) weight and length gains as compared with sham animals. Deconvolution analysis (mean +/- SEM) of plasma samples obtained every 10 minutes over 6 hours, and 14 to 16 days after second stage nephrectomy showed that NX rats had a longer GH t(1/2) (17.0 +/- 1.8 vs. 11.6 +/- 0.8 min), less GH mass secreted per burst (48 +/- 15 vs. 95 +/- 16 ng/ml/pulse), lower secretory pulse amplitude (1.9 +/- 0.5 vs. 5.8 +/- 0.9 ng/ml/min), and a reduced total GH secretion (240 +/- 69 vs. 400 +/- 56 ng/ml/6 hr) than SAL rats. Corresponding data were not significantly different between NX and SPF, or between SAL and SPF+ groups. In summary, stunted rats with chronic renal failure exhibit a prolonged GH t(1/2) and suppression of GH secretory pattern burst mass. Control data from rats with normal renal function suggest that the amplitude-specific depression of GH secretion may be attributed, at least in part, to chronic renal failure-associated calorie deficiency.

Animals↗

Severe uremia depresses the ability of perifused rat pituitary cells to secrete growth hormone in response to growth hormone releasing hormone.

To examine whether growth hormone (GH) secretion is impaired by chronic renal failure (CRF) and to gain some insight into the influence of uremia itself and associated malnutrition, the GH secretory response of dispersed anterior pituitary cells perifused with GH-releasing hormone (GHRH) was investigated in 5/6 nephrectomized (UREM, N = 15) and three groups (N = 15 each) of normal renal function, sham-operated rats under three different nutritional conditions: fed "ad libitum" (SAL), pair-fed with a diet similar to the UREM group (SPF), and pair-fed with a diet similar to the UREM group in terms of protein ingestion but calorically supplemented up to intake of SAL group (SPF+). Ten days after nephrectomy, UREM rats had severe CRF, as shown by much higher (P < 0.0001) serum urea nitrogen concentrations (X +/- mean +/- SE) than sham groups (59 +/- 6 versus 8 +/- 0, 9 +/- 0, and 5 +/- 0 mmol/L, respectively), and they were growth retarded, as shown by lower gains (P < 0.0001) in weight (13.5 +/- 2.5 versus 62 +/- 2.1, 20.5 +/- 1.9, and 50.4 +/- 1.0 g) and length (2.9 +/- 0.2 versus 5.8 +/- 0.1, 3.6 +/- 0.1, and 5.6 +/- 0.1 cm). Perifusion studies showed similar basal GH secretory rate (ng/min/10(7) cells) in the four groups. A fixed sequence of progressively increasing GHRH doses resulted in a lower overall mean GH secretion in UREM rats (15.8 +/- 1.6 ng/min/10(7) cells), as compared with SAL (50.8 +/- 9.0 ng/min/10(7) cells, P < 0.01), SPF (33.0 +/- 3.3 ng/min/10(7) cells, P < 0.05), and SPF+ (49.4 +/- 5.1 ng/min/10(7) cells, P < 0.01) groups. Analysis of dose-response curves showed that the maximal secretory response was produced by the same concentration of GHRH (10 nM) in the four groups and was lower (P < 0.01) in UREM than SAL and SPF+ rats (34.9 +/- 5.0 versus 115.7 +/- 28.4 and 98.9 +/- 9.8 ng/min/10(7) cells). The concentration of GHRH that caused the half of maximal effect was identical, close to 1 nM, in the four groups of animals. This study provides direct evidence that the ability of pituitary cells to secrete GH in response to GHRH is depressed in severe CRF. The lower secretory capacity of pituitary gland is only partly dependent on caloric malnutrition associated with CRF. Data of dose-response curves suggest that decreased GH secretion may be related to a lesser number of pituitary receptors for GHRH.

Animals↗

Chronic renal failure and human growth hormone treatment do not modify endothelium-dependent reactions in the rat aorta in vitro.

1. Growth hormone (GH) increases glomerular filtration rate and renal plasma flow and decreases renal vascular resistance. Sustained GH-induced hyperfiltration might be undesirable in children with chronic renal failure (CRF) who are receiving recombinant human GH (rhGH) therapy. 2. In order to determine the effect of CRF on vascular reactivity and the modifications induced by rhGH administration, two endothelium-dependent effects, acetylcholine relaxation and decrease of contractile response to noradrenaline, were studied in aorta segments of various groups of male Sprague-Dawley rats: CRF rats (CRF, n = 8) with serum urea nitrogen (SUN) 68 +/- 16 mg dl-1 (mean +/- SEM), CRF rats treated with intraperitoneal rhGH at 10 IU kg-1 day-1 for 13 days (CRFGH, n = 6, SUN = 88 +/- 15 mg dl-1), sham operated rats (SHAM, n = 8, SUN: 21 +/- 1 mg dl-1) and control rats (CONTROL, n = 8, SUN 20 +/- 1 mg dl-1), housed in identical conditions but without undergoing surgical intervention or manipulation. CRF was induced by 5/6 two stage nephrectomy. 3. Rats were sacrificed and a segment of thoracic aorta was immediately removed, cut into spirals, and suspended in organ baths according to standard procedures. First, dose-response curves to noradrenaline and acetylcholine relaxation, in strips previously exposed to noradrenaline, were determined. Then, the endothelium was removed and both dose-response curves were repeated. Acetylcholine induced a greater relaxation, P < 0.05, in the aorta of CONTROL rats (82.6 +/- 6.1%) as compared with SHAM (60.3 +/- 4.7%), CRF (60.0 +/- 6.8%) and CRFGH (54.8 +/- 8.2%) rats. 4. Endothelium removal only caused a greater contractile response to noradrenaline (10(-9) and 3 x 10(-9)M) in the CONTROL group, P < 0.05. 5. No differences to acetylcholine and noradrenaline responses were found among the SHAM, CRF and CRFGH groups. 6. These results suggest that the endothelium-dependent vascular reactivity was modified by the experimental protocol to induce chronic renal failure but no further changes resulted from uraemia and rhGH treatment.

Acetylcholine↗

Morphometry of uremic rat growth plate.

Growth retardation is a common manifestation of chronic renal failure in children. To gain insight into the alterations of bone growth plate of chronic uremia, a morphometric study of tibia proximal growth plate was performed in 5/6 nephrectomized rats (NX, n = 4) and sham animals (SHAM, n = 4). Toluidine blue stained sagittal sections (5-6 microns) from ethanol-fixed and methylmethacrylate-embedded tibias were analyzed. Widths (X +/- SEM) of growth plate (GPW), proliferative (PZW) and hypertrophic zones (HZW) were calculated. Results were as follows: [table: see text] Growth plate modifications in uremia are rather due to alterations in the hypertrophic than proliferative zone. This is consistent with an abnormal metabolism of condrocytes as shown by a lower mean area of extracellular matrix (EMA) per cell in the hypertrophic zone of the NX rats (0.23 vs. 0.58 microns 2).

Animals↗

Assessment of protein intake in children with chronic renal insufficiency.

Daily nitrogen intake was estimated in 19 children, aged (mean +/- SD) 9.9 +/- 5.0 (range: 1-19) years with chronic renal insufficiency (creatinine clearance 47.1 +/- 19.3 ml/min/1.73 m2, range: 11-75) by 31 three-day prospective dietary records (NIDR) and simultaneous 24-hour urine urea excretion (NIUE). Daily nitrogen intake was 11.05 +/- 3.9 g by NIDR and 8.52 +/- 3.3 g by NIUE, and a significant correlation (r = 0.61; p = 0.0003) existed between both methods of measurement. However, the difference in nitrogen intake estimated from dietary records and from 24-hour urine collection (NIDR-NIUE) was 2.5 +/- 3.3 g, greater than the mean estimated nitrogen intake calculated from both methods, (NIDR + NIUE)/2, 95% limits of agreement being +9.1 to -4.1. Thus, NIDR and NIUE values show a good correlation in children with chronic renal insufficiency, although both methods may provide quite a different estimation in a given child.

Adolescent↗

Analysis of growth in five-sixths-nephrectomized rats.

The present study was designed in an attempt to better define the pattern of growth in five-sixths-nephrectomized rats. Male Sprague-Dawley rats underwent two-stage (days 0 and 7) five-sixths nephrectomy (NX, n = 16) or sham surgery (SHAM, n = 9). At the time of sacrifice (day 21), renal failure (CRF) of NX rats was confirmed by elevated (p < or = 0.0001) serum concentrations (X +/- SEM) of urea nitrogen (SUN) (56 +/- 5 vs. 20 +/- 1 mg/dl) and creatinine (0.7 +/- 0.04 vs. 0.4 +/- 0.02 mg/dl) and reduced SUN (0.13 +/- 0.02 vs. 0.44 +/- 0.05 ml/min/100 g) and creatinine clearances (0.23 +/- 0.02 vs. 0.58 +/- 0.05 ml/min/100 g). As shown by lower cumulative gains of weight (41 +/- 6 vs. 74 +/- 4 g) and length (5.0 +/- 0.4 vs. 6.8 +/- 0.3 cm), NX rats grew subnormally. Detailed analysis of growth data revealed: (1) In spite of being identically matched in weight and length on day 0, at day 7, NX rats already weighed less than SHAM animals (147.1 +/- 2.3 vs. 153.4 +/- 1.9 g, p = 0.03). (2) From day 7 on, daily gain of weight was lower in the NX group only on days 8 (-6.08 +/- 0.52 vs. -1.60 +/- 0.69 g/100 g body weight) and 9 (-0.41 +/- 1.73 vs. 5.18 +/- 0.63 g/100 g body weight). (3) Following the early post-second-nephrectomy period, two subgroups of NX rats were clearly differentiated according to whether or not their daily growth rate was lower than that of SHAM animals. Maintained subnormal growth rate was observed in rats with severe CRF (SUN 73 +/- 5 mg/dl, range 54-90) but not in rats having milder uremia (42 +/- 3 mg/dl, range 31-51). Thus, growth in five-sixths-nephrectomized rats should be reported based on daily weight increments (g/100 g body weight). Subnormal growth can be attributed to CRF provided SUN is at least 3 times as high as normal while growth impairment of rats with less marked reduction of renal function is likely related to transient acute renal failure and postsurgical catabolic state.

Animals↗

Specific staining of glycine N-methyltransferase.

Glycine N-methyltransferase from rabbit, human, rat and pig livers was separated by isoelectric focusing and a specific functional staining method was developed through the detection of sarcosine produced from the methylation of glycine. Isozyme patterns obtained in the various species tested differ both in the number of bands and apparent isoelectric points. These differences may explain the contradictory data on the subunit structure and glycosylation status of the enzyme reported so far.

Animals↗

Nutritional status of children with moderate chronic renal failure.

Nutritional status was evaluated in 15 children (11 males) with moderate chronic renal failure (CRF). Two 3-day prospective dietary records, anthropometric measures and biochemical determinations were performed 3 months apart. Energy, protein, carbohydrate, fat, polyunsaturated, monounsaturated and saturated fatty acid intakes, expressed as percentages of international recommendations, were 87 +/- 14, 223 +/- 42, 73 +/- 12, 110 +/- 27, 55 +/- 31, 129 +/- 51 and 111 +/- 26%, respectively. The relative distribution of calories was 15 +/- 2% from proteins, 48 +/- 5% from carbohydrates and 37 +/- 5% from lipids. Anthropometric indices, expressed as standard deviation score, were: weight -0.50 +/- 0.8, height -0.94 +/- 1.3, growth velocity -0.61 +/- 1.8, triceps skinfold thickness -0.30 +/- 0.6, subscapular skinfold thickness -0.19 +/- 0.8, mid-arm muscle circumference 0.38 +/- 0.3 and body mass index -0.22 +/- 1.0. Serum concentrations of albumin, total protein, transferrin, IgG, IgA, IgM, C3 and C4 and blood lymphocyte counts were within normal limits. The mean serum insulin-like growth factor-I concentration, expressed as standard deviation score, as 0.74 +/- 1.5. No anthropometric or biochemical signs of malnutrition were found in children with moderate CRF. However, their dietary intake of calories and carbohydrates was low and the protein and saturated fatty acid intake excessively high.

Adolescent↗

Insulin-like growth factor-I gene expression in the tibial epiphyseal growth plate of growth hormone-treated uremic rats.

To identify the molecular mechanisms involved in long bone growth of uremic animals, we evaluated the effects of recombinant human growth hormone (rhGH) supplementation on whole body growth, growth plate morphometrics, and insulin-like growth factor-I (IGF-I) gene expression in the tibial epiphyseal growth plates of uremic rats. Uremia was induced by a two-stage subtotal nephrectomy (Nx) of 30-day-old rats, followed by rhGH (N = 6) or saline (N = 6) treatment from day 56 to day 70 of age. Controls (N = 4) were sham decapsulated. Treatment with rhGH on Nx animals caused: (1) a significant increase in weight, (2) longitudinal growth similar to controls, and (3) increased total growth plate width predominantly due to an increase in hypertrophic zone width. rhGH increased IGF-I mRNA abundance in both zones, but the increase was greater in the proliferative zone. These changes were accompanied by concomitant alterations in IGF-I immunoreactivity. In uremic animals, therefore, rhGH treatment induces local IGF-I gene expression in the growth plate and increases the hypertrophic zone width but not the proliferative zone width. The latter suggests resistance to IGF-I action in that zone.

Animals↗

Effect of a low sodium diet on urinary elimination of cystine in cystinuric children.

Restriction of sodium intake has been shown to decrease urinary elimination of cystine in adult subjects with cystinuria. This simple therapeutic recommendation may be particularly useful in pediatric patients whose compliance with high fluid ingestion and repeated doses of alkali is usually poor. We studied the effect of sodium intake in 5 cystinuric children (3 males) aged 5.9-9.3 years. Urinary excretion of cystine (means +/- SD) was determined at the end of two sequential 1-week periods in which sodium content of diet was modified. Reduction of sodium intake brought about significant decreases in natriuresis (6.0 +/- 2.1 vs. 1.5 +/- 0.5 mEq/kg/day, p < 0.03) and urine cystine concentration (328.0 +/- 190.7 vs. 14.1 +/- 7.4 mg/l, p < 0.02) while urine volume output remained unchanged (58.0 +/- 36.0 vs. 70.3 +/- 33.0 ml/kg/day). These findings confirm that elimination of cystine is highly influenced by sodium intake in cystinuric children and suggest that a low sodium diet may play a key-role in the treatment of pediatric patients with cystinuria.

Child↗

Effect of substituting steam-flaked sorghum for concentrate on lactation and digestion in dairy cows.

Thirty-five lactating cows (110 DIM), allotted to five dietary treatments for 70 d, were fed 0, 15, 30, or 45% of dietary DM as steam-flaked sorghum grain (360 g/L) in place of equal amounts of a mixture (DM basis) of 40% steam-rolled corn, 13% rolled barley, 20% wheat mill run, and 27% ground beet pulp in four diets. Thinly flaked sorghum grain (283 g/L) was also fed at 15% of dietary DM. The DMI tended to increase as flaked sorghum increased. Yields of milk and milk protein and percentages of milk protein and SNF increased linearly as sorghum increased. Milk yield of cows fed 15% of DM as the thinly flaked sorghum was higher than for cows fed the 360 g/L flake at 15% and similar to that of cows fed the 360 g/L flake at 30 or 45%. Feed efficiencies and changes in BW and body condition score were unaffected by treatment. As steam-flaked sorghum increased, digestibilities of DM, OM, ADF, NDF, and CP tended to decrease, except for the thinly flaked sorghum fed at 15% of DM. Apparent starch digestibility in the total tract was unaltered by diet. The 30 to 45% of DM fed as steam-flaked sorghum grain (360 g/L) increased yields of milk and milk protein, and thinly flaked sorghum (283 g/L) fed at 15% of DM increased milk yields over that of the control diet or that with the 360 g/L flake at 15% of DM.

Animal Feed↗

Effect of enzyme treatment or steam-flaking of sorghum grain on lactation and digestion in dairy cows.

Effects of addition of a fungal enzyme (reported to have amylolytic and proteolytic activities) to dry-rolled or steam-flaked sorghum grain (40% of dietary DM) were tested for 70 d with 36 lactating Holstein cows in a 2 x 2 factorial arrangement of treatments. Compared with dry-rolling, steam-flaking resulted in increased yield of milk, milk protein, and 3.5% FCM; percentage of milk protein; and efficiency of feed utilization (FCM/DMI). Milk casein (as a percentage of milk N) was not altered, but milk urea N was lower, for cows fed steam-flaked sorghum. With steam-flaking, milk fat percentage decreased, short-chain fatty acids (C8 to C14) increased, but long-chain fatty acids (C16 to C18) were not affected. No yield parameters were altered by enzyme addition, except that the percentage of lactose in milk increased (5.02 vs. 4.96%). Steam-flaking of sorghum grain increased digestibilities of DM, OM, and starch (63 vs. 57%; 66 vs. 59%; and 98 vs 83%, respectively) compared with dry rolling. Enzyme addition did not affect starch digestibility, but digestibilities of DM, OM, CP, and NDF were greater than flaked grain was treated with enzyme, resulting in significant interaction effects. This study demonstrated higher milk and milk protein yields for cows fed steam-flaked sorghum than for cows fed dry-rolled sorghum, but addition of a sorghum-specific enzyme had no significant effect.

Animal Feed↗

Renin, kallikrein and prostaglandin renal systems in normotensive boys with and without a family history of essential hypertension.

BACKGROUND: The role of the kidney in the development of essential hypertension is subject of debate. METHODS: We compared the renin, kallikrein and prostaglandin renal systems in two groups of normotensive boys, aged 7-16 years, with different degrees of risk for future hypertension: 27 had parents with essential hypertension and 12 had normotensive parents. Supine, standing and post-exercise plasma renin activity as well as levels of urinary kallikrein and prostaglandin E2 before and after exercise were measured. RESULTS: The ratio of post-exercise plasma renin activity (ng/ml/h) to 24 h urinary sodium excretion (mEq/kg/day) was lower in children with hypertensive parents (mean +/- SEM 1.86 +/- 0.24 compared with 3.62 +/- 0.94, P = 0.02). The boys with hypertensive parents had a lower ratio of urinary kallikrein to creatinine before (0.70 +/- 0.13 compared with 1.54 +/- 0.36, P = 0.01) and after exercise (0.80 +/- 0.13 compared with 1.35 +/- 0.23, P = 0.03). The ratio of urinary prostaglandin E2 to creatinine levels did not differ between the groups before or after exercise. CONCLUSION: The plasma renin activity response to exercise and urinary kallikrein excretion were decreased in boys at increased risk of future essential hypertension. These early abnormalities in the renin and kallikrein renal systems may be associated with the development of essential hypertension.

Adolescent↗

Effect of isocaloric infusion of glucose in the rumen or propionate in the duodenum.

This study was undertaken to understand better the mechanisms causing increased milk protein. Cows fed steam-flaked sorghum have increased milk protein compared with that of cows fed dry-rolled sorghum because of a large shift of starch digestion from the intestine to the rumen. Five cannulated lactating cows were infused with glucose in the rumen or with propionate in the duodenum in two trials. The experimental design was a 2 x 2 Latin square with 7 d of adjustment and 7 d of infusion. During the experiment, cows received a TMR containing 19.3% CP and 1.56 Mcal/kg of NEL (on a DM basis); alfalfa hay and dry-rolled sorghum grain were the principal ingredients. Similar concentrations in feces of cows among propionate treatments suggested complete absorption of infused propionate. Milk yield did not differ, but protein percentage of milk was higher (2.88 versus 2.72%) for cows infused ruminally with glucose than for those infused in the duodenum with propionate. For the respective treatments, duodenal flows were 2.11 and 1.76 kg/d for microbial protein and 3.44 and 2.73 kg/d for total CP (or 85 and 74% of CP intake). These data demonstrate that increased propionate availability for gluconeogenesis and a possible sparing of essential AA did not result in increased milk protein content, but ruminal infusion of glucose, which tended to increase microbial protein synthesis, did increase the protein percentage of milk.

Adenosine Triphosphate↗