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Biomedical subjects

A Oliva

Publications and source records attributed to A Oliva.

At least 19 recordsLinked to original sources

Adrenal sparing surgery in the treatment of renal cell carcinoma: when is it possible?

Despite the fairly low incidence of adrenal involvement, adrenalectomy continues to be performed routinely as part of radical nephrectomy. With the recent development of modern imaging techniques and their widespread use, the frequency of small, low stage renal cell carcinomas (RCC) has grown considerably, giving rise to more conservative surgical approaches. We conducted a retrospective study in order to evaluate the incidence and characteristics of adrenal metastasis in RCC, trying to clarify the accuracy of computerized tomography (CT) in the diagnosis and the real need for adrenalectomy during surgery for RCC. The medical records of 192 patients undergoing radical nephrectomy and ipsilateral adrenalectomy for localized or advanced RCC, from 1996 to 2001, were analyzed retrospectively. We considered two subgroups of patients, 73 with stage T1-2 disease (group 1) and 119 with T3-4N0-1M0-1 disease (group 2) according to the 1997 TNM classification. In all cases, a blinded review of the preoperative abdominal CT was performed and an adrenal gland was considered to be abnormal if there was any aberration. Histopathology records of the surgical specimens were examined to determine the accuracy of the CT in identifying adrenal involvement by RCC. Descriptive statistics were used to evaluate the collected data. The overall incidence of adrenal metastasis was 4.1%. Mean renal tumor size in patients with adrenal involvement was 7.8 cm. The tumor stage correlated with the probability of adrenal spread ( P<0.05), with T1-2 tumors accounting for 1.3% of cases only. An adrenal gland was diagnosed as abnormal on preoperative CT in 20 patients (10.4%). CT scans had 87.5% sensitivity, 92.9% specificity, 99.4% negative predictive value and 35% positive predictive value for adrenal involvement by RCC. Adrenal involvement is not likely in patients with localized early stage RCC, and adrenalectomy is unnecessary in such cases, particularly when the CT is negative. However, radical nephrectomy, including removal of the ipsilateral adrenal gland, should be performed in patients with large, high risk tumors.

Adrenal Gland Neoplasms↗

Are extended biopsies really necessary to improve prostate cancer detection?

The aim of this study is to understand the value of specific sites in extended peripheral and transition zone biopsy schemes in order to define the optimal systematic biopsy regimen correlated with the percentage of positivity of each single bioptic site. A total of 165 consecutive patients underwent transrectal ultrasonography examination to detect prostate cancer followed by a lesion-directed and systematic 14-step biopsy scheme. The detection rate was examined for the lesion-directed and for each zone region biopsy. The frequency of positive biopsies in the various prostate regions was determined to evaluate the diagnostic yield of each biopsy site. Analysis was stratified for prostate-specific antigen (PSA), free-to-total PSA ratio, age, prostate size and digital rectal examination. The biopsy protocol detected 40% of patients (66/165) as positive and 55.1% (91/165) as negative for cancer. Standard sextant biopsy was expected to detect only 51 cancer on 66, lateral peripheral (PZ), transition (TZ) and central zone (CZ) biopsies only 56 cancer on 66, while the combination of sextant, PZ, TZ and CZ biopsies, for a total of 14 zone biopsies, detected 64 on 66 patients with cancer (97%) at recruitment. Sampling only the eight prostate regions with higher frequency of positive cancer biopsy was expected to detect 61 cancer patients against the 64 found with the 14-step scheme. This eight-biopsy regimen outperforms the conventional sextant regimen in cancer detection rate (93 vs 77%) and has an overall detection rate lower by only 3.1% (36.9 vs 40%) compared to the 14-biopsy regimen. This difference in detection rate is even smaller in patients with PSA values <10 ng/ml, age <70 y and prostate size <50 ml. This eight-biopsy scheme, including sampling in PZ and TZ toward the base, should be considered in an initial biopsy scheme to maintain a similar detection rate of an extensive biopsy scheme reducing the number of biopsies.

Biopsy↗

Seasonal patterns of arthropods occurring on sheltered and unsheltered pig carcasses in Buenos Aires Province (Argentina).

Differences in the succession of insects and other Arthropoda (invertebrate animals with jointed legs), on domestic pig carcasses placed under a roof and under the open sky have been studied in Buenos Aires Province, Argentina (latitude 34 degrees 45'S) in all the seasons of the year. Faunal associations proved different for each treatment in winter: the common bluebottle Calliphora vicina was found in both, but on the sheltered carcass Cochliomyia macellaria and the rare Phaenicia cluvia were found as well. In the fall, the difference between sheltered and unsheltered carcasses was small (six species on the former and five species on the latter); in spring and summer, the difference was negligible.

Animals↗

Biocompatibility studies on biodegradable polyester-based composites of human osteoblasts: a preliminary screening.

A series of biodegradable composites with natural hydroxyapatite, designed for possible use in orthopedics applications, were preliminarily screened for biocompatibility by employing primary cultures of human osteoblasts in a direct contact method. The cells were seeded at low density onto the materials under investigation and allowed to grow for 2 weeks. They then were analyzed for morphology, proliferation, viability, alkaline phosphatase activity (AP), osteocalcin (OC) production, and extracellular matrix mineralization. The results showed that all materials have good biocompatibility. Cell viability tests demonstrated that in all cases the values were comparable to the control, and the addition of hydroxyapatite always resulted in an enhancement of performance with respect to the plain polymer. AP and OC analysis confirmed that all composites allowed the expression of phenotypic markers. Scanning electron microscopy provided direct evidence of intense cell adhesion and proliferation on the tested materials.

Biocompatible Materials↗

Novel graft PLLA-based copolymers: potential of their application to particle technology.

This study describes the synthesis of novel biodegradable graft copolymers based on a backbone of poly (L-lactic acid) (PLLA) on which short blocks of polyacrylamide (PAcr) were grafted. Preliminary results of their potential in the field of controlled-release technologies also have been reported. The copolymers have been synthesized through the radical polymerization of acrylamide initiated by a peroxide in the presence of PLLA. Two different methodologies of synthesis, namely, in solution and in emulsion, have been tested. The structure of the copolymers was studied by (1)H-NMR and infrared spectroscopy and by differential scanning calorimetry (DSC) and cytotoxicity tests were conducted to assess their biocompatibility. The copolymers were used to prepare particles by the emulsion-solvent evaporation technique. The shapes and dimensions of the particles were dependent on the polymer type and concentration used. The surfaces of the particles were modified by the presence of polyacrylamide residues, as demonstrated by zeta-potential measurements. The release behavior of the particles was assessed by encapsulating rhodamine B as the model compound. The release was faster for the particles prepared by the grafted polymer as a consequence of its increased hydrophilicity. Based on these novel biomaterials, preliminary results suggest a potential of the particles for peroral or parenteral drug delivery.

Absorption↗

Interleukin-4 and interleukin-5 gene expression and inflammation in the mucus-secreting glands and subepithelial tissue of smokers with chronic bronchitis. Lack of relationship with CD8(+) cells.

We wished to determine if the inflammatory cells surrounding the airway mucus-secreting glands in chronic bronchitis (CB) were associated with interleukin (IL)-4 and IL-5 mRNA expression and whether the CD8 T cell population expressed these cytokines. Digoxigenin-labeled IL-4 and IL-5 antisense RNA probes were used to detect gene expression in 11 asymptomic smokers (AS), 11 smokers with CB alone with normal lung function, and 10 smokers with chronic bronchitis and coexisting chronic obstructive pulmonary disease (CB+COPD; FEV(1)% of predicted of 43-77% and FEV(1)/ FVC of 51-68%). There were approximately three times as many IL-4 than IL-5 mRNA(+) cells. The highest number of IL-4 mRNA(+) cells were in the submucosal glands of the CB group with normal lung function (216/mm(2)), significantly higher than the values in either the AS (63/mm(2)) or the CB+COPD (87/mm(2)) groups, respectively (p < 0.01). There were similar group differences when the total numbers of inflammatory cells were compared. Accordingly, there was a positive correlation between the number of IL-4 mRNA(+) cells and the total number of inflammatory cells in both the subepithelium and glandular compartments (r = 0.60; p = 0.01 and r = 0.70; p = 0.02, respectively). There were no significant associations between the numbers of CD8(+) and IL-4 or IL-5 mRNA(+) cells. Of 1328 IL-4(+) and 1404 CD8(+) cells counted none was double labeled. Of 727 IL-5(+) and 1569 CD8(+) cells, none was double labeled. In contrast, as a positive control, 34% of tumor necrosis factor (TNF)-alpha(+) cells were also CD8(+) and 15% of CD8(+) cells were TNF-alpha positive. Thus, cells other than the CD8(+) phenotype produce IL-4 and IL-5 in CB. We conclude that there is increased inflammation and IL-4 gene expression in the mucus-secreting glands and the airway mucosa of smokers with bronchitis: both are lower in those with CB and coexisting COPD suggesting that airway inflammation in CB is reduced when airway obstruction develops.

Aged↗

Environment as a risk factor for male infertility.

Infertility affects 15% of couples in Western countries. Infertility is defined as the inability to conceive after 1 year of attempts without contraception, but it is not synonymous with sterility. Between 30 and 50% of infertile couples are infertile due to male reasons, mainly due to sperm production disorders. Although some risk factors, most of which are infectious, have been identified, there is still much uncertainty about the origins of male infertility.

Environmental Exposure↗

Insects of forensic significance in Argentina.

Records from forensic expertises and trappings with beef baits conducted in Buenos Aires, Argentina (34 degrees 36'S), show that the dominating species are widespread ones (Calliphora vicina and Phaenicia sericata), with different behaviour in each large latitudinal zone. It is suggested that the range of the yearly photoperiod variation has an influence in the behaviour of the blowflies, making up for differences in the succession patterns. The Calliphorid blowflies Cochliomyia macellaria and Chysomya albiceps were found on indoors corpses; the latter also on outdoors corpses when blood was shed, and in that case as primary. Three species of beetles of the genus Dermestes, which had been associated with mummified remains, appeared 10-30 days after death. The Silphid beetle Hyponecrodes sp. cf. erythrura was found on outdoor copses in rural environments. The Nitidulid beetle Carpophilus hemipterus was found in association with the cheese skipper Piophila sp. (Diptera: Piophilidae) in medullar cavities of bones after ca. 30 days; to this association is often added the Clerid Necrobia rufipes. Lepidoptera Tineidae appear on the head of mummified indoors corpses. North of parallel 32 degrees S, the Muscid grave-fly Ophyra sp. was found breeding on a corpse outdoors in summer. A division by latitude and climate is proposed for Argentina, and an extended system is proposed for the world.

Animals↗

Mechanism of olefin cyclopropanation by diazomethane catalyzed by palladium dicarboxylates: a density functional study.

The reaction of diazomethane with ethylene in the presence of palladium diformate has been studied through density functional calculations. Several mechanistic paths leading to the formation of cyclopropane have been studied. The results obtained show that the reaction of palladium diformate with diazomethane is more favorable than the reaction with ethylene. The reaction with diazomethane may lead to two different isomeric complexes: a methylene-inserted complex and a palladium-carbene complex. Insertion of methylene is the most favorable process, but the resulting complex is not suitable for cyclopropanation. The reaction with two additional diazomethane molecules makes the formation of the bismethylene-inserted palladium-carbene complex favorable. Attack of ethylene on this palladium-carbene complex leads to the formation of cyclopropane.

Journal Article↗

Genes modulated by histone acetylation as new effectors of butyrate activity.

A wealth of evidence correlates the chemopreventive activity of a fiber-rich diet with the production of butyrate. In order to identify the genes transcriptionally modulated by the molecule, we analyzed the expression profile of butyrate-treated colon cancer cells by means of cDNA expression arrays. Moreover, the effect of trichostatin A, a specific histone deacetylase inhibitor, was studied. A superimposable group of 23 genes out of 588 investigated is modulated by both butyrate and trichostatin A. Among them, a major target was tob-1, a gene involved in the control of cell cycle. tob-1 is also up-regulated by butyrate in a neuroblastoma-derived cell line, and its overexpression in the colon cells caused growth arrest. Our findings represent an extensive analysis of genes modulated by butyrate and identify completely new effectors of its biological activities.

Acetylation↗

Comparative study of protein molecular weights by size-exclusion chromatography and laser-light scattering.

High-performance size-exclusion chromatography (SEC) based on UV-Vis detection is a relative technique for molecular weight determination whereas procedure based on multi-angle laser light scattering (MALLS) is both rapid and absolute. The two methods using recombinant human growth hormone (rHGH) and beta-lactoglobulin samples were compared. A calibration curve for the chromatographic system was generated based on standard proteins and the data were fitted by least squares to a third order polynomial model. The molecular weight from the conventional SEC method for both proteins was higher than the reported values. The molecular weight of rHGH from MALLS was 23.1+/-0.57 and 21.2+/-0.80 kDa using differential refractive index (SEC-MALLS/RI) and UV (SEC-MALLS/UV-Vis) detectors as mass detectors. Both values agree, within experimental error with the molecular weight sequence of rHGH, 22.1 kDa. In contrast, the molecular weight from LS for beta-lactoglobulin was 22.5+/-0.55 kDa by SEC-MALLS/RI and 23.0+/-1.22 kDa by SEC-MALLS/UV-Vis, respectively, values always higher than those supplied by the manufacturer, 18.4 kDa. The reproducibility of the SEC-MALLS/UV-Vis method versus the SEC-MALLS/RI method was performed using the concordance correlation coefficient. The method's reproducibility was accepted by assuming a precision of 98% and a 1% loss in precision.

Chromatography, Gel↗

Contribution of environmental factors to the risk of male infertility.

BACKGROUND: An increasing number of reports suggest that chemical and physical agents in the environment, introduced and spread by human activity, may affect male fertility in humans. We investigated the relationships between exposure to environmental agents and seminal characteristics, and the concentrations of reproductive hormones in the serum of men seeking infertility treatment. METHODS: We studied 225 male partners from consecutively recruited couples, who had their first infertility consultation between 1995 and 1998, in the Litoral Sur region of Argentina, one of the most productive farming regions in the world. RESULTS: A multivariate logistic regression model showed that exposure to pesticides and solvents is significantly associated with sperm threshold values well below the limit for male fertility. We also found that men exposed to pesticides had higher serum oestradiol concentrations, and that men exposed to solvents had lower LH concentrations than non-exposed men. All of these effects were greater in men with primary infertility than in men with secondary infertility. CONCLUSION: We have shown that environmental factors contribute to the severity of infertility, and that this may worsen the effects of pre-existing genetic or medical risk factors.

Agriculture↗

Pyrimidine-2,4,6-Triones: a new effective and selective class of matrix metalloproteinase inhibitors.

Matrix metalloproteinases (MMPs) are a family of zinc endopeptidases that have been implicated in various disease processes. Different classes of MMP inhibitors, including hydroxamic acids, phosphinic acids and thiols, have been previously described. Most of these mimic peptides and most likely bind in a similar way to the corresponding peptide substrates. Here we describe pyrimidine-triones as a completely new class of metalloprotease inhibitors. While the pyrimidine-trione template is used as the zinc-chelating moiety, the substituents have been optimized to yield inhibitors comparable in their inhibition efficiency of matrix metalloproteinases to hydroxamic acid derivatives such as batimastat. However, they are much more specific for a small subgroup of MMPs, namely the gelatinases (MMP-2 and MMP-9).

Chelating Agents↗

Lispro insulin in type 1 diabetic patients on a Mediterranean or normal diet: a randomized, cross-over comparative study with regular insulin.

Lispro (LP) and regular human (HR) insulins were compared in Type 1 diabetic (T1DM) patients on either a Mediterranean diet or normal diet. Twelve T1DM patients were recruited and randomized into two groups of 6, groups A and B. They were treated in different sequences (in 3-month intervals for 1 year). Group A: LP insulin and normal diet, LP insulin and Mediterranean diet, regular insulin and Mediterranean diet, regular insulin and normal diet. Group B: regular insulin and normal diet, regular insulin and Mediterranean diet, LP insulin and Mediterranean diet, LP insulin and normal diet. Each patient was treated with rapid acting insulin, either LP insulin or HR insulin, before each main meal and a dose of slow acting insulin at bedtime. Every 15 days the glycemic control, the incidence and frequency of hypoglycemic episodes, and any adverse events were evaluated. Every 3 months, hematology and a chemistry panel, pre- and post-prandial glycemic and insulinemic profiles were evaluated in all patients. HbA1c levels significantly decreased in LP patients on normal diet, post-prandial glycemic levels were significantly lower in LP than in HR patients from 30 min onwards, 15-min post-prandial insulin levels higher in LP- than in HR-treated patients, and hypoglycemic episodes were significantly less in LP- than in HR-treated patients. LP insulin, irrespective of the type of diet, results in more effective glycemic control, significantly reduces hypoglycemic episodes as opposed to traditional insulin therapy and seems to be more effective with a normal diet than with a Mediterranean diet.

Adolescent↗

Development of two high-performance liquid chromatographic methods for the analysis and characterization of insulin and its degradation products in pharmaceutical preparations.

Two high-performance liquid chromatography methods either in reversed-phase or as size exclusion separation mode were developed and validated for the analysis of insulin and its degradation products in pharmaceutical preparations. The results show the reliability of the analytical methods for the intended used. The static and dynamic light scattering were used to characterize the insulin and its derivatives. The absolute molecular weight of human insulin monomer and dimer were 5800 and 12400 Da respectively whereas its z-average root mean square radius were 21.6+/-0.4 and 40.5+/-0.7 nm, respectively. In contrast, the hydrodynamic diameter varied between 2.69 and 5.50 nm, depending of the association behavior of insulin.

Chromatography, High Pressure Liquid↗

Statistical assessment of between batch stability equivalence.

A statistical method for testing the equivalence between batches regarding their stability is proposed. This method is based on the statistical linear model making use of a set of dummy variables to code the different batches. The method gives us the point estimates of the slope and zero intercept of one batch, and the differences and the corresponding confidence intervals with the remaining batches. In a second step, zero intercepts and slopes are estimated for all the batches. Stability equivalence assessment is based on the comparison of the confidence intervals for the differences between batches with the maximum difference allowable. The main advantages of this method are the possibility to compare several batches, to disclose the equivalence stability criteria from the statistical hypothesis about the equality between slopes, and the joint estimated of the residual variance whatever the decision to pool or not the data from different batches. This method is illustrated with two data set; the first one, previously published by other authors, involved six batches; the second data set include two batches and arose in a stability study of a commercial human insulin conducted in our laboratory.

Confidence Intervals↗

Angular studies of potential electron emission in the interaction of slow ions with Al surfaces

We report energy distributions of electrons emitted from Al surfaces under impact by 1 keV Ar+ and 1-5 keV Ne+ ions. The variation of the energy distributions with the angle of incidence is different for both ions and provides information on the mechanism responsible for electron emission. For Ar+ electron emission results mainly from Auger neutralization, while for Ne+ an important emission mechanism is the decay of plasmon excitations. We find a transition between surface and bulk plasmon excitations as the energy of the ion is increased.

Journal Article↗

p27Kip1 accumulation is associated with retinoic-induced neuroblastoma differentiation: evidence of a decreased proteasome-dependent degradation.

Development of human neuroblastoma is due to an arrest in the differentiation program of neural crest sympathoadrenal progenitor cells. However, neuroblastomas, as well as their derived cell lines, maintain the potentiality of terminal differentiation. We investigated the molecular mechanisms by which retinoic acid, a molecule introduced in clinical trials for chemotherapy, induces differentiation in neuroblastoma cell lines. Our findings demonstrate that the retinoic acid-dependent growth arrest of LAN-5 neuroblastoma cell line is associated to a very large accumulation (>tenfold) of p27Kip1 protein, a cyclin-dependent kinase inhibitor; the protein binds and inhibits cyclin-dependent kinase 2, 4 and 6 activities, thus hampering pRb and p107 phosphorylation. p27Kip1 build-up was observable as an early phenomenon (12 - 24 h) after retinoic exposure and resulted in a time-dependent accumulation of high quantities of a free p27Kip1 form. Furthermore, retinoic treatment causes an increase of cyclin-dependent kinase 5 level and activity; however, immunoprecipitation studies proved the absence of interaction with p27kip1. No noticeable variation of other components of G1 phase cell cycle engine was observed. Pulse-chase experiments showed a remarkable elongation of p27Kip1 half-life in retinoic-treated LAN-5, while no enhancement of p27Kip1 gene expression and of the translational efficiency of its messenger RNA were demonstrated. In vivo degradation of p27Kip1 was sensitive to two highly specific proteasome inhibitors, LLnL and lactacystin, while the calpain inhibitor II ALLM and the cysteine protease inhibitor E64 did not modify the level of the protein. LLnL treatment caused a very rapid (2 h) build-up of the Cdk inhibitor content and the accumulation of higher molecular weight anti-p27Kip1 immunoreactive bands, which probably represent ubiquitinated forms of the protein. Finally, in vitro experiments demonstrated that extracts prepared from retinoic-treated LAN-5 cells degraded recombinant p27Kip1 at a rate remarkably slower than the untreated cells. Our results indicate that retinoic acid strongly increases p27Kip1 levels by down-regulating the ubiquitin-proteasome p27Kip1 degrading pathway.

Cell Cycle↗