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Biomedical subjects

R Pereira

Publications and source records attributed to R Pereira.

At least 73 records · Page 4Linked to original sources

Changes of intestinal alkaline phosphatase produced by cholecalciferol or 1,25-dihydroxyvitamin D3 in vitamin D-deficient chicks.

Treatment with cholecalciferol or 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) increases activity and changes electrophoretic mobility of alkaline phosphatase (alkPase) from duodenal brush border of vitamin D-deprived chicks. Three of the four molecular forms of the enzyme show reduced velocity of migration 9 h after 1,25(OH)2D3 or 24 h after vitamin D3. This change is reversed about 48 h later, when mobility of those bands is higher than that of controls. Incubation of enzyme preparations with exogenous neuraminidase produces the same electrophoretic modifications observed during the early stage, indicating that they are due to desialylation. Cholecalciferol or 1,25(OH)2D3 increase sialidase activity of duodenal brush border. This increment precedes that of alkPase and could account for the initial desialylation and moderate rise of alkPase. Cycloheximide markedly reduces alkPase in rachitic chicks and blocks the increase of the enzyme activity produced by vitamin D3, but does not modify the rise of sialidase or the reduction of alkPase electrophoretic mobility. The bimodal response of alkPase to 1,25(OH)2D3 or cholecalciferol comprises two different mechanisms: during a first stage, epigenetic modifications of preexisting enzyme can be triggered by the increased Ca2+ levels; in a second phase, there is activation of enzyme synthesis.

Alkaline Phosphatase↗

Phospholipids and sialic acid changes produced by vitamin D3 on intestinal mitochondria.

Vitamin D3 administration to vitamin D-deficient chicks produces, 24 hours after treatment, a large increment of phospholipids in mitochondria from intestinal mucosa. Proportion of the different phospholipid classes and fatty acid composition of the organelles were not modified by that treatment. A time course study of the effects of 1,25(OH)2D3 on calcium absorption and sialic acid content of intestinal mitochondria glycoproteins showed that both effects were correlated. The results suggest that either vitamin D or the increase of calcium transfer are involved in the make up of intestinal mitochondria membranes.

Animals↗

Brachial plexus injury following brachial plexus block.

A patient developed paralysis over the left upper limb 2 days after an otherwise uneventful supraclavicular brachial plexus block. Symptoms continued for 8 weeks after the block. The various possible causes for this complication are discussed. Although brachial plexus injury following the block is rare, some recommendations are made to reduce the incidence of this complication.

Adult↗

Phosphate intestinal secretion and absorption by isolated ileal loop: effects of cholecalciferol and diet phosphate.

The effect of diet phosphate content and cholecalciferol on intestinal phosphate secretion and absorption was investigated in rachitic chicks. Phosphate absorption was determined by the in situ ligated loop technique. Phosphate secretion was estimated by a method proposed by the authors. Hydroxyapatite, placed in the lumen of a ligated loop, acts as trapping agent of 32P leaving the intestinal tissue. The fraction of rapid exchangeability of tissue phosphate was taken as the precursor pool of secreted phosphate. Control chicks fed diets containing 0.3% P (group 1) or 1.0% (group 2) showed similar Pi absorption; the secretion was larger for group 2. After cholecalciferol treatment for 2 or 4 consecutive days an increment of Pi absorption with simultaneous reduction of Pi secretion was evident for both groups of animals. Chicks treated for 7 days gave values similar to those of controls. It is concluded that the regulation of intestinal phosphate absorption and secretion could be one important mean of homeostatic control. Intestinal phosphate movement is adapted to dietary phosphate and is partially independent of cholecalciferol.

Animals↗

The effect of AY-9944 on yeast sterol and sterol ester metabolism.

The effects of the hypocholesterolemic drug AY-9944 (trans-1,4-bis(2-chlorobenzylaminoethyl)cyclohexane dihydrochloride) at two concentrations (10(-4) M and 5 X 10(-4) M) on the synthesis of sterols and sterol esters by Saccharomyces cerevisiae were investigated. Although growth was not markedly affected by the drug, there was a decrease in the free sterol to sterol ester ratio with increased drug concentration. A concomitant increase in the saturated fatty acids esterified to sterol relative to the unsaturated fatty acids was also noted in response to increased drug concentration. Ergosterol accounted for 94.7% of the free sterol in the control culture and for 87.8% of the 5 X 10(-4) M drug-treated culture, respectively. However, in the sterol ester fraction, the ergosterol content decreased from a value of 45.1% in the control culture to 2.4% in the 5 X 10(-4) M AY-9944 treated culture. The sterol ester fraction simultaneously showed increased levels of the delta 8 sterol, fecosterol, in response to increased drug concentration from a 7.4% control value to 57.4% in the 5 X 10(-4) M drug-treated culture. The accumulation of the delta 8 sterol suggests that the site of action of the drug is probably at the delta 8 to delta 7 isomerase step in the biosynthesis of ergosterol. The fact that ergosterol is retained as the major free sterol suggests a biological advantage to the retention of this particular sterol. In addition, the near normal growth in the presence of the drug, in spite of the occurrence of an altered sterol ester profile, indicates that the composition of the sterol ester fraction is not as critical as the free sterol fraction.

Cholesterol↗

The inheritance of schizophrenia spectrum disorders: a reanalysis of the Danish adoptee study data.

Rosenthal and colleagues earlier compared the frequency of schizophrenia spectrum disorders in two groups of persons adopted in infancy or early childhood: those with a psychotic parent (index group) and those whose biological parents had never had a psychiatric diagnosis or treatment (control group). They found significantly more disorder in the index group. Reanalysis of the original material using DSM-III and stricter exclusionary criteria applied to the parents yielded three times as many schizophrenia spectrum disorders in the index as in the control group. This difference remained statistically significant, supporting the operation of genetic factors in the transmission of the traits comprising the schizophrenic spectrum of disorders.

Adoption↗

Effects of vitamin D3 on the uptake and release of calcium by isolated intestinal mitochondria.

Administration of vitamin D3 or 1,25 (OH)2D3 to rachitic chicks produces a decrease of 45Ca uptake by mitochondria from intestinal mucosa. This effect of vitamin D3 shows tissue specificity, since it was not observed in liver mitochondria from the same animals. The Km values were similar (about 10 microM) for intestinal mitochondria from rachitic and treated animals. The Ca2+ efflux in previously loaded mitochondria was not changed by treatment. The Ca content of recently isolated mitochondria was strikingly lower after vitamin D3 administration. It is concluded that vitamin D3 may participate in the mechanism which regulates the intramitochondrial Ca concentration.

Animals↗

Lack of relationship between activity of intestinal alkaline phosphatase and calcium or phosphate absorption.

The effects of vitamin D3 and the aqueous extract of Solanum malacoxylon on intestinal alkaline phosphatase and tissue phosphate content were studied on rachitic chicks treated with large doses of ethane-1-hydroxy-1,1 diphosphonate (EHDP). The EHDP treatment blocks the increase of intestinal calcium or phosphate absorption induced by the vitamin D3, while it has no effects on the rise of intestinal alkaline phosphatase activity or the increment in tissue phosphate content. The lack of correlation between the increment of alkaline phosphatase and that of Ca or phosphate absorption in vitamin D3 plus EHDP treated chicks excludes a participation of the alkaline phosphatase in the mechanism of Ca or P intestinal absorption. The Ca or phosphorus absorption are elicited specifically by 1,25-(OH)2-D3, while alkaline phosphatase activity and phosphate tissue concentration respond to a broader spectrum of stimuli.

Alkaline Phosphatase↗

Effect of dietary phosphate on intestinal calcium and phosphate absorption.

Intestinal Ca and P absorption was investigated on rachitic chicks raised on diets with a 1% Ca and 0.3% or 1% P contents. 45Ca and 32P absorption was determined by the technique of the isolated gut sac in vivo. In addition, 32P transport was also measured by the everted gut sac procedure in vitro. Treatment with vit. D3 during 7 days increased the 45Ca absorption in animals fed diets containing 0.3% or 1% P. 32P absorption showed an increase after 2 days of treatment and a decrease afterwards. The reduction of 32P absorption was larger in animals fed diet with 1% P. Study of 32P transport with the everted gut sac technique showed an increase after vit. D3 and a loss of intracellular P, regardless the duration of treatment.

Animals↗

Age-related changes in calcium homeostatic mechanisms in synaptosomes in relation with working memory deficiency.

Aging is associated with alterations in different systems that govern neuronal calcium homeostasis. This study was designed to determine whether any of these alterations may contribute to the decline in spatial working memory that is observed in old rats. Several parameters [initial (5 s) and steady state (15 min) 45Ca2+ uptake, FCCP-releaseable 45Ca2+, [Ca2+]i levels, depolarization-induced phosphoprotein (P97, PP65, P42) dephosphorylation and acetylcholine levels and release) involved in calcium homeostasis/signaling were determined in whole brain synaptosomes derived from adult (9-month-old) and old (24-month-old) rats that were evaluated for spatial memory performance in the eight-arm radial maze. The neurochemical analysis indicated that both the 9- and 24-month-old rats were impaired with respect to 3-month-old animals. When learners (animals reaching criterion; RC) were compared to memory impaired rats (MI), it was found that the FCCP-releaseable 45Ca2+ of synaptosomes, that reflects mitochondrial calcium, was lower in the MI than the RC rats and was correlated with the behavioral performance of the rats in their first testing sessions. The results suggest that the loss of calcium uptake capacity in synaptic mitochondria during aging may be associated with impaired working memory in old animals.

Acetylcholine↗

Altered cell calcium regulation in synaptosomes and brain cells of the 30-month-old rat: prominent effects in hippocampus.

A deficient regulation of neuronal cytosolic calcium levels has been suggested to play a role in the pathogenesis of neurodegeneration. However, evidence for an alteration in cytosolic calcium regulation in old age is at present controversial. The present work was aimed at studying whether changes in synaptosomal calcium homeostasis in 30-month-old rats are uniform throughout the brain or affect specific brain regions. A second question addressed in this work is whether the effect of ageing on calcium homeostasis is restricted to the nerve terminal or a more general process affecting also cell bodies. To study these questions cytosolic calcium regulation was studied in parallel in synaptosomes and a preparation of acutely dissociated brain cells obtained from different regions of 3- and 30-month-old rats. 45Ca2+ accumulation and distribution in mitochondria (assessed as FCCP-releasable 45Ca2+) was also studied. Mean [Ca2+]i obtained at rest and after high K+ depolarization were unchanged in cerebral cortex synaptosomes but increased in hippocampal synaptosomes at 30 months. Resting [Ca2+]i also increased with age in hippocampal, but not cerebral cortex cells, whereas the increase in [Ca2+]i obtained by depolarization was larger in both brain regions. Calcium compartmentation in mitochondria from hippocampal neurons incubated under high K+ conditions was also decreased with ageing. An altered calcium regulation in cell bodies and synaptic terminals in the hippocampus may be involved in the development of functional impairments in the hippocampal formation.

Aging↗

An ultrastructural, microanalytical, and spectroscopic study of bone from a transgenic mouse with a COL1.A1 pro-alpha-1 mutation.

A line of transgenic mice have been investigated that expressed moderate levels of an internally deleted human gene for the pro alpha (I) chain of type I procollagen. These mice expressed the gene at approximately 50% that of the endogenous gene. The gene construct was modeled after a sporadic in-frame deletion of the human gene that produced a lethal variant of osteogenesis imperfecta by causing biosynthesis of shortened pro alpha (I) chains. Periera et al. (1993) reported extensive fracturing in these mice with femurs that were shorter in length and bone that had decreased ash weight, mineral, and collagen content. These workers demonstrated an increased brittleness in bone using biomechanical measurements. The functional consequences of these mutant genes were examined in both transgenic and in normal littermate mice to determine if a valid model at the ultrastructural and analytical level had been produced for OI. X-ray microanalysis of bone mineral demonstrated a significantly lower calcium-to-phosphorus (Ca/P) molar ratio in transgenic mouse bone than in normal littermates; this was a feature of human OI bone. Fourier transform infrared spectroscopy confirmed that the mineral present was apatitic in nature despite the lower Ca/P molar ratio. Alizarin red skeletal staining showed the presence of multiple fracture calluses on the ribs and on the long bones of some of the transgenic mice, this was not seen on normal littermates. No light microscopic differences were observed between normal and transgenic mice; however, many ultrastructural correlates with human OI were observed in the transmission electron microscope. Anomalous fibrils associated with type I collagen, and an amorphous calcified material was observed lining the cartilage, extending beyond the lamina limitans in young transgenic mice.

Aging↗

Simultaneous pancreas-kidney transplantation: five-year results from a single center.

We report the 5-year results of our simultaneous pancreas-kidney transplantation (SPKT) program, started on May 2, 2000. Forty-two SPKT were performed on 42 type I diabetic patients with chronic renal failure. The procedure was performed with enteric diversion and vascular anastomosis to the iliac vessels. Immunosuppressive protocol included antithymocyte globulin, tacrolimus, mycophenolate mofetil, and steroids. The 24 women and 18 men had a mean age of 33.5 +/- 6.3 years and mean 22.8 +/- 14.2 years time of diabetes evolution. Forty patients had been on dialysis for 34.3 +/- 24.1 months, and two were preemptive transplantations. Acute rejection episodes were treated in eight patients (19.1%): in three cases they affected both organs; in two only the kidney was affected; and the other three were pancreas graft rejections. The incidence of postoperative complications requiring re-operation was 42.9%, mostly pancreas graft related. Two patients died, one due to cardiovascular disease; the other was transplant related. Three kidney grafts were lost, and the causes were immunologic, thrombosis, and patient death. Pancreas graft loss occurred in seven patients: thrombosis (n = 3); infection (n = 3); immunologic (n = 1). The patients with surviving grafts were doing well, with normal kidney and pancreas function: serum creatinine = 0.89 +/- 0.15 mg/dL; fasting blood glucose = 79 +/- 16 mg/dL; HbA1c = 4.7 +/- 1.1%. The 1-year patient, kidney, and pancreas survival rates were 97.3%, 94.6%, and 83.8% and 5-year values, 91.7%, 89.2%, and 78.7%, respectively. In conclusion, these results are similar to the most recent UNOS/IPTR reports, leading us to consider our experience with SPKT very positive.

Adult↗