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Biomedical subjects

M Rosa

Publications and source records attributed to M Rosa.

At least 19 recordsLinked to original sources
PubMed2001

Renal hemodynamic response to maximal vasodilating stimulus in healthy older subjects.

BACKGROUND: It is still unclear whether age per se is associated with preservation of renal functional reserve, that is, of the increase in glomerular filtration rate (GFR) induced by appropriate vasodilating stimulus. METHODS: To gain insights into this issue, we evaluated the renal response to a maximal vasodilating stimulus, represented by the combined infusion of mixed amino acid solution (AA) and dopamine at renal dose (D), in 10 young subjects (median age of 30 years, range of 19 to 32) and in 11 subjects of older age (median age of 67 years, range of 65 to 76). Two further age-matched groups of young (N = 15) and older (N = 11) living kidney donors underwent renal needle biopsy immediately before nephrectomy to perform semiquantitative scoring (0 to 3) of arteriosclerosis in intrarenal arteries. All of the study subjects were nonsmokers with healthy status proven by extensive diagnostic evaluation excluding any risk factor of renal dysfunction. RESULTS: Basal renal plasma flow (RPF) and GFR were proportionally lower in older subjects (RPF, 361 +/- 29 vs. 618 +/- 34 mL/min/1.73 m(2), P < 0.001; GFR, 79 +/- 4 vs. 127 +/- 5.8 mL/min/1.73 m(2), P < 0.001). After AA + D, a significant increase of RPF and GFR was observed in both groups, but the older subjects exhibited a smaller percentage increment (RPF, 25.5 +/- 4.8 vs. 42.4 +/- 5.8, P < 0.05; GFR, 19.6 +/- 5.7 vs. + 33.8 +/- 6.4, P < 0.05). Furthermore, the maximal vasodilating stimulus was not able to restore renal hemodynamics in older subjects to the level measured in young controls at baseline. Renal vascular resistances were higher (P < 0.05) in the older subjects both at baseline (0.19 +/- 0.02 vs. 0.09 +/- 0.004 mm Hg/mL/min) and after AA + D (0.14 +/- 0.01 vs. 0.06 +/- 0.004). Light microscopy examination detected the presence of a greater degree of arteriosclerosis at the level of interlobular and arcuate arteries (0.89 +/- 0.15 vs. 0.45 +/- 0.08) and interstitial fibrosis/tubular atrophy (1.18 +/- 0.13 vs. 0.53 +/- 0.13) in older than in young subjects. CONCLUSIONS: Therefore, aging has adverse effects on renal function despite the absence of any risk factor for renal disease, including chronic smoking: (1) GFR and RPF are lower, and (2) the renal response to maximal vasodilating stimulus is impaired. These aging-related alterations of renal hemodynamics are possibly due to organic lesions in renal vasculature.

Adult↗
PubMed2001

Identification of novel porcine endogenous betaretrovirus sequences in miniature swine.

PCR amplification of genomic DNA from miniature swine peripheral blood lymphocytes, using primers corresponding to highly conserved regions of the polymerase (pol) gene, allowed the identification of two novel porcine endogenous retrovirus (PERV) sequences, PMSN-1 and PMSN-4. Phylogenetic analyses of the nucleotide sequences of PMSN-1 and PMSN-4 revealed them to be most closely related to betaretroviruses. The identification of PERVs belonging to the Betaretrovirus genus shows that endogenous retroviruses of this family are more broadly represented in mammalian species than previously appreciated. Both sequences contained inactivating mutations, implying that these particular loci are defective. However, Southern blot analysis showed additional copies of closely related proviruses in the miniature swine genome. Analyses of fetal and adult miniature swine tissues revealed a broad mRNA expression pattern of both PMSN-1 and PMSN-4. The most abundant expression was detected in whole bone marrow c-kit(+) (CD117(+)) progenitor bone marrow cells, fetal liver, salivary gland, and thymus. It appears unlikely that functional loci encoding these novel PERV sequences exist, but this remains to be established. The betaretrovirus sequences described in this report will allow such investigations to be actively pursued.

Animals↗
PubMed2000

Sex-of-offspring-specific transmission ratio distortion on mouse chromosome X.

During our study of the DDK syndrome, we observed sex ratio distortion in favor of males among the offspring of F(1) backcrosses between the C57BL/6 and DDK strains. We also observed significant and reproducible transmission ratio distortion in favor of the inheritance of DDK alleles at loci on chromosome X among female offspring but not among male offspring in (C57BL/6 x DDK)F(1) x C57BL/6 and (C57BL/6-Pgk1(a) x DDK)F(1) x C57BL/6 backcrosses. The observed transmission ratio distortion is maximum at DXMit210 in the central region of chromosome X and decreases progressively at proximal and distal loci, in a manner consistent with the predictions of a single distorted locus model. DXMit210 is closely linked to two distortion-controlling loci (Dcsx1 and Dcsx2) described previously in interspecific backcrosses. Our analysis suggests that the female-offspring-specific transmission ratio distortion we observe is likely to be the result of the death of embryos of particular genotypic combinations. In addition, we confirm the previous suggestion that the transmission ratio distortion observed on chromosome X in interspecific backcrosses is also the result of loss of embryos.

Animals↗
PubMed2000

Heritability of the maternal meiotic drive system linked to Om and high-resolution mapping of the Responder locus in mouse.

Matings between (C57BL/6 x DDK)F(1) females and C57BL/6 males result in a significant excess of offspring inheriting maternal DDK alleles in the central region of mouse chromosome 11 due to meiotic drive at the second meiotic division. We have shown previously that the locus subject to selection is in the vicinity of D11Mit66, a marker closely linked to the Om locus that controls the preimplantation embryo-lethal phenotype known as the "DDK syndrome." We have also shown that observation of meiotic drive in this system depends upon the genotype of the sire. Here we show that females that are heterozygous at Om retain the meiotic drive phenotype and define a 0.32-cM candidate interval for the Responder locus in this drive system. In addition, analysis of the inheritance of alleles at Om among the offspring of F(1) intercrosses indicates that the effect of the sire is determined by the sperm genotype at Om or a locus linked to Om.

Animals↗
PubMed2000

Retinoids in breast cancer prevention and treatment. A review of the literature.

During the last three decades, research focused on cancer treatment has led to the development of many cytotoxic agents. Despite the fact that these efforts have significantly improved the prognosis of certain malignancies such as some lymphomas, leukemias and testicular carcinomas, other tumors such as ovarian, lung and metastatic breast cancer are still associated with a poor prognosis. An innovative approach has recently emerged, thanks to a better understanding of tumor cell biology and many efforts are aimed at finding compounds capable of restoring a more differentiated phenotype to tumor cells, thereby reducing the tumor's aggressiveness and ultimately reverting it to its normal counterpart [1, 2]. Retinoids are the prototype of this new therapeutical approach called "differentiation therapy".

Animals↗
PubMed2000

Integrative medicine: a paradigm shift in medical education and practice.

The use of alternative/complementary medicine has been increasing considerably. Conventional medicine must begin to address issues related to the use, safety, regulation, research and education of alternative/complementary medicine. Integrative medicine combines conventional medicine and alternative complementary practices. Integrative medicine is an innovative approach to medicine and medical education. It involves the understanding of the interaction of the mind, body and spirit and how to interpret this relationship in the dynamics of health and disease. Integrative medicine shifts the orientation of the medical practice from disease based approach to a healing based approach. It does not reject conventional medicine nor uncritically accepts unconventional practices. Integrative medicine is an effective, more fulfilling human approach to medicine based on the benefit of the patient by following good medicine practices in a scientific manner.

Complementary Therapies↗
PubMed1999

Chromosome aberrations induced by aphidicolin.

The expression of aphidicolin (apc)-produced common fragile sites and chromosome aberrations observed 24 h after apc treatment was studied in a normal individual. The chromosome lesions (gaps and breaks) induced by apc are expressed as full chromosomal aberrations in later cell divisions. We compared chromosome rearrangements or anomalies induced by apc (detected in 45.4% of metaphases analyzed) with those present in human neoplasia or involved in primate evolution. We found that 55.7% of deletions observed in our study coincided with deletions implicated in several types of neoplasia. However, none of 49 translocations observed in our study coincided with those described as recurrently associated with human neoplasia, probably due to their unbalanced nature. When chromosome aberrations detected in our study (only deletions and inversions were taken into account) were compared to those involved in primate evolution, we found a low rate of coincidence. The low coincidence between chromosome alterations in neoplasia and evolution and those observed in our study could be explained because we analyzed chromosome alterations that had not been selected, whereas those present in chromosome evolution and in neoplasia had been subjected to a selection process.

Aphidicolin↗
PubMed1996

Mutation analysis in Duchenne and Becker muscular dystrophy patients from Bulgaria shows a peculiar distribution of breakpoints by intron.

For the first time in Bulgaria, a deletion/duplication screening was performed on a group of 84 unrelated Duchenne/Becker muscular dystrophy patients, and the breakpoint distribution in the dystrophin gene was analyzed. Intragenic deletions were detected in 67.8% of patients, and intragenic duplications in 2.4%. A peculiar distribution of deletion breakpoints was found. Only 13.2% of the deletion breakpoints fell in the "classical" hot spot in intron 44, whereas the majority (> 54%) were located within the segment encompassing introns 45-51, which includes intron 50, the richest in breakpoints (16%) in the Bulgarian sample. Comparison with data from Greece and Turkey points at the probable existence of a deletion hot spot within intron 50, which might be a characteristic of populations of the Balkan region.

Bulgaria↗
PubMed1996

Prognostic factors in mild dystrophinopathies.

One hundred twenty five patients from 105 families were considered, showing in-frame intragenic deletion or duplication of the dystrophin gene and/or abnormal dystrophin on muscle biopsy. According to clinical status of patients, the affection was classified as subclinical, benign, moderate or severe. Significant decrease of dystrophin abundance was observed with increasing clinical severity (p < 0.05). Detailed clinical data were available in 68 patients in whom a long-term follow-up (6-39 years) was obtained. Functional performance at different ages and disease endpoints were recorded in order to analyze the rate of disease progression. We identified three different disease courses: stable, slow and rapid progression. We observed a significantly lower level of dystrophin and immunohistochemical score (p < 0.05 vs. the other courses) in patients with rapid course. Deletion or duplication in the 5' end of the gene was associated with poor prognosis. Prognosis was substantially better, showing a stable course, in patients with large deletions or duplications in the proximal rod region. These subjects often suffered from a cramps/myalgia syndrome or experienced rhabdomyolisis. Cardiac involvement was detected in 65% of cases. A significant increase of right ventricular volume was seen in all clinical groups (p < 0.05). A left ventricular dilation was observed in 25% and a decreased ejection fraction in 29% of our patients. The reduction of ejection fraction and the increase of left ventricular volume were age-related. Since sudden death may occur as a consequence of cardiomyopathy, severe left ventricular dysfunction in dystrophinopathic patients is another important adverse prognostic factor, although not always directly correlated with skeletal muscle impairment.

Adolescent↗
PubMed1996

Does the presence of ANCA in patients with ulcerative colitis necessarily imply renal involvement?

BACKGROUND: ANCA are thought to play a pathogenic role in renal vasculitis. ANCA may also be detected in patients with diseases not usually associated with renal pathology, such as ulcerative colitis. Our study was conducted to determine if the presence of ANCA in patients with ulcerative colitis is associated with renal pathology. METHODS: Eight ANCA-positive and five ANCA-negative patients with a histological and endoscopic diagnosis of active ulcerative colitis were investigated. Repeated complete urinalyses and determination of microalbuminuria and creatinine clearance were performed. Serum IgG and IgA ANCA were evaluated in all patients by indirect immunofluorescence and ELISA, and when detected the antibodies were further characterized by alpha granules preparation, myeloperoxidase, lactoferrin, and cathepsin G. RESULTS: In both ANCA-positive and ANCA-negative patients renal function was normal or near normal and urinalyses (including microalbuminuria) failed to disclose any abnormalities. ANCA exhibited a perinuclear pattern in all ANCA-positive patients. Interestingly, none of the ANCA-positive patients had antibodies to myeloperoxidase or to alpha granules which are usually found in the sera of patients with ANCA-associated vasculitis, and only one had antibodies to lactoferrin. The ANCA specificity remained undetermined in the remaining seven patients. At the end of the 1-year observation period, all ANCA-positive patients remained ANCA-positive without developing symptoms, signs or laboratory abnormalities consistent with renal involvement. CONCLUSIONS: Renal damage was not observed in ANCA-positive patients with ulcerative colitis even after 1 year of follow-up, suggesting that the ANCA found in these patients do not share the antigenic targets with the ANCA commonly found in renal vasculitis. Therefore the potential of ANCA of inducing renal lesions (if any) is dependent on their own antigenic specificity.

Adolescent↗
PubMed1996

Effects of hypercholesterolemia of renal hemodynamics: study in patients with nephrotic syndrome.

Experimental and clinical studies have demonstrated a positive relationship between hyperlipidemia and rate of progression of renal disease, suggesting that lipids can induce or aggravate glomerular injury mainly by interacting with mesangial cells. Nevertheless, recently has been demonstrated that increased cholesterol levels can also induce endothelial cell dysfunction. Thus, since endothelium is known to play a major role in modulating the vascular tone, we have tested the possibility that hypercholesterolemia impairs the renal hemodynamics in patients with active nephrotic syndrome and elevated serum cholesterol levels. In this single-blind, nonrandom study, 12 patients were treated with pravastatin (group T, treated, n = 12) and 8 with placebo (group C, controls, n = 8). The controls were studied after the pravastatin group had been completed. Before starting the treatment the patients underwent basal determinations including routine laboratory investigations and PAH and inulin clearances. The same determinations were repeated after 48 h, and 6 and 12 weeks from the beginning of the treatment. The study at 48 h was performed to see if pravastatin had a direct, cholesterol-independent effect on renal function. The following basal results were reported (mean +/- SEM; group T vs. group C): serum cholesterol (mmol/l) 9.7 +/- 0.4 vs. 9.1 +/- 0.3 (NS); proteinuria (g/24 h): 6.2 +/- 0.2 vs. 7.0 +/- 0.7 (NS); PAH clearance (ml/min): 353 +/- 21 vs. 385 +/- 31 (NS); inulin clearance (ml/min): 62.5 +/- 7.7 vs. 67 +/- 9.3 (NS). After 48 h, no changes were observed in both groups. Subsequently, in group T, the following percentage changes of basal levels were observed: serum cholesterol -21.4 +/- 3.2% at 6 weeks (p < 0.05) and -34.9 +/- 3.2% at 12 weeks (p < 0.01); inulin clearance +3 +/- 3.7% at 6 weeks (NS) and +9.3 +/- 2.9% at 12 weeks (p < 0.05); PAH clearance +7 +/- 3.1% at 6 weeks (p < 0.05) and +21.2 +/- 5.5% at 12 weeks (p < 0.01). By contrast, no significant changes of these parameters occurred in group C at any time, so that the percent changes of baseline values of CPAH were significantly greater in group T (at 6 weeks: p < 0.05; at 12 weeks p < 0.005). These results indicate that the reduction of cholesterol is associated with a significant increase in renal plasma flow, thus, suggesting that hypercholesterolemia may actually impair the renal hemodynamics. We speculate that this effect may contribute to increase the risk of ischemic acute renal failure in nephrotic patients and, along with changes induced in the mesangium by other mechanisms, to contribute to the progression of renal disease.

Adult↗
PubMed1995

Household and community determinants of exposure to involuntary smoking: a study of urinary cotinine in children and adolescents.

The study examines the role of several potential predictors of urinary cotinine levels in a cross-sectional sample of 1,072 nonsmoking children and adolescents in Latium, Italy, during 1990-1991. As expected, there was a strong relation between passive exposure to smoking and the amount of maternal and paternal self-reported smoking. The urinary cotinine level increased with a decreasing level of paternal education and with an increasing index of household crowding; self-report of recent exposure to smoking outside the home was a strong predictor of the biologic marker. The analysis was then restricted to 346 subjects whose parents claimed that they were nonsmokers and that there were no smokers at home. In this group, however, 57 children reported some active smoking at home by their parents. Those with parents suspected to be "deceivers" had higher level of urinary cotinine than did those truly not exposed. In addition, urinary cotinine in this group was clearly associated with duration of exposure to smoking outside home. The study indicates that both factors related to family circumstances and exposure outside the household setting are strong determinants of urinary cotinine levels. The finding may be considered a direct confirmation that passive smoking among children should be viewed as a specific community responsibility.

Adolescent↗
PubMed1995

Solid-phase extraction of nicotine and its metabolites for high-performance liquid chromatographic determination in urine.

A solid-phase extraction, using Extrelut-1 glass columns, has been applied to urine samples of both passive and active smokers for high-performance liquid chromatographic determination of nicotine and its metabolites cotinine and trans-3'-hydroxycotinine. Chromatography was performed using a reversed-phase LC8DB column and a mobile phase consisting of water-acetonitrile (80:9, v/v) containing 5 ml triethylamine, 670 mg/l sodium heptanesulphonate, and 0.034 M each of K2HPO4 and citric acid (pH 4.4), at a flow-rate of 1.6 ml/min. The results obtained indicate that solid-phase extraction is a reliable and quick procedure which can be applied also to other nicotine metabolites.

Chromatography, High Pressure Liquid↗