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Biomedical subjects

A Valenzuela

Publications and source records attributed to A Valenzuela.

At least 37 records · Page 2Linked to original sources

Consumption pattern of dietary fats in Chile: n-6 and n-3 fatty acids.

Chile consumes both vegetable and animal fats. Vegetable oils are almost totally imported but animal fats, mainly from marine origin, are locally produced. The country is the second world producer of fish meal and fish oil, and fish oil has been incorporated into the human nutrition through the manufacture of blends of vegetable oil with fractions of deodorized fish oil. Consumption of such oils contributes as a significant source of n-6 and n-3 fatty acids, mainly for the low-income consumers. The use of fish meal and fish oil for animal nutrition is also an additional source of n-3 fatty acids for the Chilean population. Pork, poultry and eggs are important sources of essential fatty acids, especially long-chain n-3 fatty acids. As result of the consumption of these products, milk from low-income Chilean mothers shows significantly higher total n-3 fatty acids relative to mothers from the USA and Germany. Safety concerns about fats consumption in Chile are regulated by a Food Safety Codex recently promulgated which follows FAO/WHO Codex Alimentarius directives.

Animals↗

Effect of dietary hydrogenated fish oil on the plasma lipoprotein profile and on the fatty acid composition of different tissues on the rat.

Dietary fatty acids are actively incorporated into membrane lipids, and fat intake can modify the composition and the biochemical activity of cellular membranes and the pattern of plasma lipoproteins. Industrial hydrogenation of polyunsaturated oils leads to the formation of isomeric trans fatty acids which are incorporated into cellular membranes when they are present in the diet. The trans fatty acid amount present in hydrogenated oils depends on the degree of hydrogenation, being high for partially hydrogenated oils and low for highly hydrogenated oils. Hydrogenated fish oil is widely used in some countries for the production of margarine and industrial fats. This study compares the fatty acid composition of plasma, erythrocytes, subcutaneous adipose tissue, and hepatic microsomal membranes and the plasma lipoprotein profile after feeding rats with a synthetic diet containing either fish oil, partially hydrogenated fish oil, or highly hydrogenated fish oil. It is observed that the tissue content of monounsaturated fatty acids increases and that the content of polyunsaturated fatty acids decreases after an increase of the degree of hydrogenation of the dietary fat. Tissues from animals fed partially hydrogenated fish oil show significant amounts of trans fatty acids only. The plasma triacylglyceride composition and the lipoprotein profile are also altered by the degree of hydrogenation of the dietary fat. Triacylglycerides decrease after highly hydrogenated fat feeding only. Total cholesterol and low-density lipoprotein cholesterol are significantly increased after partially hydrogenated fat feeding. Although no direct evidence is presented, this effect may be attributable to the high content of trans isomers of this dietary fat which nutritionally may behave as saturated fatty acids.

Adipose Tissue↗

Trans fatty acid isomers in human health and in the food industry.

Trans fatty acids are unsaturated fatty acids with at least one double bond in the trans configuration. These fatty acids occur naturally in dairy and other natural fats and in some plants. However, industrial hydrogenation of vegetable or marine oils is largely the main source of trans fatty acids in our diet. The metabolic effect of trans isomers are today a matter of controversy generating diverse extreme positions in light of biochemical, nutritional, and epidemiological studies. Trans fatty acids also have been implicated in the etiology of various metabolic and functional disorders, but the main concern about its health effects arose because the structural similarity of these isomers to saturated fatty acids, the lack of specific metabolic functions, and its competition with essential fatty acids. The ingestion of trans fatty acids increases low density lipoprotein (LDL) to a degree similar to that of saturated fats, but it also reduces high density lipoproteins (HDL), therefore trans isomers are considered more atherogenic than saturated fatty acids. Trans isomers increase lipoprotein(a), a non-dietary-related risk of atherogenesis, to levels higher than the corresponding chain-length saturated fatty acid. There is little evidence that trans fatty acids are related to cancer risk at any of the major cancer sites. Considerable improvement has been obtained with respect to the metabolic effect of trans fatty acids due the development of analytical procedures to evaluate the different isomers in both biological and food samples. The oleochemical food industries have developed several strategies to reduce the trans content of hydrogenated oils, and now margarine and other hydrogenated-derived products containing low trans or virtually zero trans are available and can be obtained in the retail market. The present review provides an outline of the present status of trans fatty acids including origin, analytical procedures, estimated ingestion, metabolic effects, efforts to reduce trans isomers in our diet, and considerations for future prospects on trans isomers.

Dietary Fats↗

Methods for identification of 28 burn victims following a 1996 bus accident in Spain.

A car collided head-on with a bus containing 56 passengers plus the driver. A few seconds after the crash, the bus caught fire and 28 persons (15 male and 13 female) lost their lives. All the deceased were almost completely incinerated. To establish the identity of the victims, the judge in charge of the case designated a multidisciplinary Identification Commission. Postmortem procedures included a general external examination, routine photographs, dental examination, dental (intraoral and extraoral) and general radiographs (chest, ankle, etc.), and complementary biological methods for identification (e.g., DNA analysis). The antemortem information, including dental and medical records available, were transcribed onto the INTERPOL disaster victim identification forms. The detailed ante- and postmortem information were compared manually. In this disaster dental identity could be established in 57% of the victims, whereas dental evidence did not allow by itself the identification of 12 burned victims. Odontological examination and complementary radiographic procedures were found to be accurate, economic and rapid methods of identifying badly burned victims in this bus accident.

Accidents, Traffic↗

Experimental studies on the effect of lidocaine on wound healing.

Local anesthetics have several effects on wound healing. In experimental studies, procaine at high concentrations has been proved to retard healing in surgical wounds by diminishing the synthesis of mucopolysaccharides and hence probably collagen. Other studies have shown that lidocaine and bupivacaine inhibit collagen synthesis in fibroblast tissue cultures in rats. This study was designed to evaluate the effect of lidocaine on wound healing. An experimental, prospective, comparative, crossover and double-blind study was designed. Forty male guinea pigs, weighing 300 to 600 g, were randomly assigned to two groups. In control group A (20 animals), skin and subcutaneous tissue in a clean wound were incised and infiltrated with regular saline solution; in group B 20 animals were infiltrated with 1% lidocaine. All animals were sacrificed on day 8 and evaluated for breaking strength, number of collagen fibers by morphometry, and histologic examination of collagenization, edema, vascularity, and presence of acute and chronic inflammatory cells. The histopathologic appearance of tissues infiltrated with lidocaine did not vary consistently in relation to collagenization, edema, or acute and chronic inflammatory processes. The mean breaking strength between both groups was not statistically significant (p = 0.120). Important statistical differences were observed in vascularity (p < 0.003) and morphometric results (p < 0.001), where collagen was found in small amounts in the lidocaine group. The results of this study suggest that local infiltration of lidocaine produces significant histopathologic changes, but it does not substantially alter wound healing as there were no differences in the breaking strength of the wounds.

Anesthetics, Local↗

Effect of the degree of hydrogenation of dietary fish oil on the trans fatty acid content and enzymatic activity of rat hepatic microsomes.

The degree of fat hydrogenation and the trans fatty acid content of the diet affect the fatty acid composition of membranes, and the amount and the activity of some membrane enzymes. We describe the effects of four isocaloric diets containing either sunflower oil (SO, 0% trans), fish oil (FO, 0.5% trans), partially hydrogenated fish oil (PHFO, 30% trans), or highly hydrogenated fish oil (HHFO, 3.6% trans) as fat sources on the lipid composition and the trans fatty acid content of rat hepatic microsomes. We also describe the effect of these diets on the cytochrome P-450 content and on the aminopyrine N-demethylase, aniline hydroxylase, and UDP-glucuronyl transferase microsomal activities. Cytochrome P-450 content was dependent on the degree of unsaturation of the diet, being higher for the FO-containing diet and lower for the HHFO diet. Aminopyrine N-demethylase activity also correlated with the degree of unsaturation of the diet as did the cytochrome P-450 content did (FO > SO > PHFO > HHFO). Aniline hydroxylase activity appeared to be independent of the degree of unsaturation of the dietary fat, but correlated with the trans fatty acid content of the diet, which was also reflected in the trans content of the microsomal membranes. UDP-glucuronyl transferase activity was higher for the FO-containing diet than for the SO diet, showing intermediate values after the PHFO and HHFO diets.

Animals↗

The mouse stargazer gene encodes a neuronal Ca2+-channel gamma subunit.

Stargazer mice have spike-wave seizures characteristic of absence epilepsy, with accompanying defects in the cerebellum and inner ear. We describe here a novel gene, Cacng2, whose expression is disrupted in two stargazer alleles. It encodes a 36-kD protein (stargazin) with structural similarity to the gamma subunit of skeletal muscle voltage-gated calcium (Ca2+) channels. Stargazin is brain-specific and, like other neuronal Ca2+-channel subunits, is enriched in synaptic plasma membranes. In vitro, stargazin increases steady-state inactivation of alpha1 class A Ca2+ channels. The anticipated effect in stargazer mutants, inappropriate Ca2+ entry, may contribute to their more pronounced seizure phenotype compared with other mouse absence models with Ca2+-channel defects. The discovery that the stargazer gene encodes a gamma subunit completes the identification of the major subunit types for neuronal Ca2+ channels, namely alpha1, alpha2delta, beta and gamma, providing a new opportunity to understand how these channels function in the mammalian brain and how they may be targeted in the treatment of neuroexcitability disorders.

Amino Acid Sequence↗

Enzymatic and extraenzymatic role of ecto-adenosine deaminase in lymphocytes.

Adenosine deaminase (ADA, EC 3.5.4.4) is an enzyme of the purine metabolism which has been the object of considerable interest mainly because the congenital defect causes severe combined immunodeficiency (SCID). In the last 10 years, ADA, which was considered to be cytosolic, has been found on the cell surface of many cells and, therefore, it can be considered an ecto-enzyme. There is recent evidence about a specific role of ecto-ADA, which is different from that of intracellular ADA. Apart from degrading extracellular adenosine (Ado) or 2'-deoxyadenosine (dAdo), which are toxic for lymphocytes, ecto-ADA has an extraenzymatic function via its interaction with CD26. ADA/CD26 interaction results in co-stimulatory signals in T cells. This co-stimulation is blocked by HIV-1, thus evidencing a role for ecto-ADA in the pathophysiology of AIDS. The fact that, besides CD26, ADA can interact with different cell-surface proteins opens new perspectives in the research for a role of ecto-ADA in the function of the immune system and in the interactions that take place between different cells in the development of the immune system. The most interesting aspect is the possible participation of the ecto-enzyme in cell-to-cell contacts during ontogenesis and maturation of immunocompetent cells.

Acquired Immunodeficiency Syndrome↗

Genetic and physical maps of the stargazer locus on mouse chromosome 15.

The stargazer mouse mutation causes absence seizures that are more prolonged and frequent than any other petit mal mouse model. Stargazer mice also have an ataxic gait and vestibular problems, including a distinctive head-tossing motion. From the genotyping of a large intersubspecific cross, a panel of 53 recombinant DNAs between D15Mit29 and D15Mit2 has been assembled, and a fine genetic map of the stargazer region has been constructed on mouse Chromosome 15. The stargazer locus has been mapped between D15Mit30 and the parvalbumin gene, and six candidate genes have been excluded by genetic linkage analysis. A physical contig of YACs, BACs, and P1s stretching 1.1 Mb from D15Mit30 to the somatostatin receptor 3 gene is reported, and the DNA interval including the stargazer locus has been narrowed to 150 kb.

Animals↗

Adenosine deaminase binding to human CD26 is inhibited by HIV-1 envelope glycoprotein gp120 and viral particles.

CD26, known to be the adenosine deaminase (ADA)-binding protein, has been implicated in HIV infection. Several studies have revealed a correlation between depletion of CD4+/CD26+ T lymphocytes, increased serum levels of ADA, and the evolution of AIDS in infected individuals. We show that in human B and T cell lines, irrespective of CD4 expression, 125I-labeled ADA binding to CD26 is inhibited by recombinant soluble HIV-1 envelope glycoprotein gp120 and by HIV-1 infectious particles. Accordingly, an anti-CD4 mAb, which inhibits the binding of gp120 to CD4 and blocks viral infection, did not affect inhibition of 125I-labeled ADA binding to CD26 by HIV particles. On the other hand, mAbs directed against the V3 loop and the C-terminal region of gp120 abolished completely the inhibitory effect. Overlapping synthetic peptides covering the entire gp120 sequence were tested to map the region in gp120 responsible for ADA binding inhibition. Only peptides in the C3 region significantly inhibited the binding of ADA to CD26. These results provide indirect evidence for the interaction of gp120 with CD26 and indicate that a specific function of gp120 is the inhibition of ADA binding to CD26 in both CD4+ and CD4- cells. Because ADA deficiency leads to severe combined immunodefiency syndrome, it remains possible that HIV particle-mediated blockade of ADA-CD26 interaction may have significant consequences in the pathogenesis of AIDS.

Adenosine Deaminase↗

Pseudopeptide TASP inhibitors of HIV entry bind specifically to a 95-kDa cell surface protein.

The template assembled synthetic peptide constructs (TASP), pentavalently presenting the tripeptide KPR or RPK, are potent and specific inhibitors of human immunodeficiency virus (HIV) infection by preventing viral entry into permissive cells. Here the 5[KPsi(CH2N)PR]-TASP construct, Psi(CH2N) for reduced peptide bond, was used in studies to demonstrate its specific binding to a 95-kDa cell surface protein ligand. Compared to its nonreduced 5[KPR]-TASP counterpart, the pseudopeptide 5[KPsi(CH2N)PR]-TASP manifested higher affinity to bind to its cell surface ligand, increased activity to inhibit HIV infection, and resistance to degradation when incubated in serum from an HIV-1 seropositive individual. In ligand blotting experiments, the biotin-labeled 5[KPsi(CH2N)PR]-TASP identified a single 95-kDa protein in crude cell extracts. This 95-kDa protein (p95) is expressed on the cell surface since surface iodination of cells resulted in its labeling, and moreover, following incubation of cells with the biotin-labeled 5[KPsi(CH2N)PR]-TASP, the p95.TASP complex was recovered by affinity chromatography using avidin-agarose. All anti-HIV TASP constructs but not their control derivatives affected the binding of biotin-labeled 5[KPsi(CH2N)PR]-TASP to p95, thus emphasizing the specific nature of this binding. Since 5[KPsi(CH2N)PR]-TASP does not interact with HIV-envelope glycoproteins, our results suggest that TASP inhibitors mediate directly or indirectly a block in HIV-mediated membrane fusion process by binding to the cell surface expressed p95.

Flow Cytometry↗

HIV-1 envelope gp120 and viral particles block adenosine deaminase binding to human CD26.

CD26, known to be the adenosine deaminase (ADA) binding protein, has been implicated in HIV infection. In human B and T cell lines we show that, irrespective of CD4 expression, 125I-labeled ADA binding to CD26 is inhibited by recombinant soluble HIV-1 envelope glycoprotein gp120 and by HIV-1 infectious particles. Overlapping synthetic peptides covering the entire gp120 sequence were tested to map the region in gp120 responsible for ADA binding inhibition. Only peptides in the C3 region significantly inhibited the binding of ADA to CD26. These results indicate that a specific function of gp120 is the inhibition of ADA binding to CD26 in both CD4+ and CD4- cells. Since the interaction ecto-ADA/CD26 is required for the activation of T cells, it remains possible that HIV particle-mediated blockade of ecto-ADA/CD26 interaction may have significant consequences in the pathogenesis of AIDS disease.

Adenosine Deaminase↗

Comparison of aceclofenac with piroxicam in the treatment of osteoarthritis.

A multicentre, double-blind, randomised, parallel group study was undertaken to investigate the efficacy and safety of aceclofenac (123 patients, 100 mg twice daily) in comparison to piroxicam (117 patients, 20 mg once daily and placebo once daily) in patients with osteoarthritis of the knee. The treatment period of two months was preceded by a washout period of one week duration. On completion of the study, patients in both aceclofenac and piroxicam-treated groups exhibited significant improvement in pain intensity and functional capacity of the affected knee, as represented by the Osteoarthritis Severity Index (OSI) (p < 0.0001 and p < 0.001 respectively). This was further substantiated following the patient's assessment of pain intensity using the Visual Analogue Scale (VAS), in which significant improvements were demonstrated at all time points for each treatment group (p < 0.001). Although both treatment groups showed a significant improvement in all investigator's clinical assessments (functional exploration of the knee, knee flexion and extension (EXT)), there were no significant differences between the groups. There was, however, a more rapid improvement in knee flexion in the aceclofenac group after 15 days of treatment. Both aceclofenac and piroxicam were well tolerated by patients, the most commonly reported adverse events being gastrointestinal, although their incidence was low. Only 24 patients on aceclofenac, as opposed to 33 on piroxicam complained of dyspepsia, epigastralgia and pyrosis. While 7 patients in each group were withdrawn because of adverse events, only one patient with piroxicam was withdrawn because of severe upper gastrointestinal bleeding. Twice as many reports of fecal blood loss were made in the piroxicam group in comparison to the aceclofenac group. In summary, this study confirms the therapeutic efficacy of aceclofenac and suggests that it is a well-tolerated alternative NSAID to piroxicam in the treatment of osteoarthritis.

Adult↗

Antioxidant-related enzymes in myocardial zones and human pericardial fluid in relation to the cause of death.

The aim of this work was to shed light on hypoxic and ischemic processes in the heart that may lead to irreversible or lethal myocardial injury. We determined malondialdehyde (MDA) and glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities in human cardiac tissues from 45 medico-legal autopsies of persons who died from different causes. Samples were taken from three different areas of myocardium: the anterior and posterior walls of the left ventricle, and the interventricular septum. We used light microscopy to examine the heart sections (hematoxylin-eosin and Masson's trichromic stains), and studied the K+(Na+ ratio and pericardial fluid. A decrease in GSH-Px activity was found in cases with severe atherosclerosis of the coronary artery in comparison with the group with slight or moderate atherosclerosis. Postmortem activities of GSH-Px and SOD were significantly different in the three myocardial zones studied. An increase in GSH-Px activity in the interventricular septum was noted in cases of cardiac deaths. Antioxidant-related enzymes such as GSH-Px and SOD can therefore be regarded as new biochemical markers indicative of myocardial hypoxia. The possible applications to the postmortem diagnosis of the cause of death are discussed.

Autopsy↗

Radiographic comparison of the lumbar spine for positive identification of human remains. A case report.

A comparison of antemortem and postmortem abdominal radiographs showing the lumbar spine was used to establish a positive identification of an unknown cadaver. A positive matching of similar unique skeletal feature, including large osteophytes of the third, fourth, and fifth lumbar vertebrae, distinctive features of the spinous and transverse processes, and identical angulation of an existing right lumbar scoliosis was established. A criticism of the methods used to establish the identification is presented.

Aged↗

Neutralizing antibodies against the V3 loop of human immunodeficiency virus type 1 gp120 block the CD4-dependent and -independent binding of virus to cells.

The CD4 molecule is an essential receptor for human immunodeficiency virus type 1 (HIV-1) through high-affinity interactions with the viral external envelope glycoprotein gp120. Previously, neutralizing monoclonal antibodies (MAbs) specific to the third hypervariable domain of gp120 (the V3 loop) have been thought to block HIV infection without affecting the binding of HIV particles to CD4-expressing human cells. However, here we demonstrate that this conclusion was not correct and was due to the use of soluble gp120 instead of HIV particles. Indeed, neutralizing anti-V3 loop MAbs inhibited completely the binding and entry of HIV particles into CD4+ human cells. In contrast, the binding of virus was only partially inhibited by neutralizing anti-CD4 MAbs against the gp120 binding site in CD4, which, like the anti-V3 loop MAbs, completely inhibited HIV entry and infection. Nonneutralizing control MAbs against either the V3 loop or the N or C terminus of gp120 had no significant effect on HIV binding and entry. HIV-1 particles were also found to bind human and murine cells expressing or not expressing the human CD4 molecule. Interestingly, the binding of HIV to CD4+ murine cells was inhibited by both anti-V3 and anti-CD4 MAbs, whereas the binding to human and murine CD4- cells was affected only by anti-V3 loop MAbs. The effect of anti-V3 loop neutralizing MAbs on the HIV binding to cells appears not to be the direct consequence of gp120 shedding from HIV particles or of a decreased affinity of CD4 or gp120 for binding to its surface counterpart. Taken together, our results suggest the existence of CD4-dependent and -independent binding events involved in the attachment of HIV particles to cells; in both of these events, the V3 loop plays a critical role. As murine cells lack the specific cofactor CXCR4 for HIV-1 entry, other cell surface molecules besides CD4 might be implicated in stable binding of HIV particles to cells.

Animals↗

An improved method to recover saliva from human skin: the double swab technique.

Human bite mark evidence is often found in violent crimes. Due to the difficulties of physically comparing an injury site on elastic and curved skin surfaces to the teeth of a suspect, the authors have considered using salivary DNA evidence to identify the bite perpetrator. Several techniques were evaluated to determine the best method of recovering saliva from human skin before extracting genomic DNA from the collection substrate. A classical stain recovery technique using a wet cotton swab was tested against one utilizing a wet filter paper. Additionally, a new method, referred to as the double swab technique, using a wet cotton swab followed by a dry cotton swab was also evaluated. After recovering a dried saliva stain, DNA was extracted using the modified Chelex method, quantified using the slot-blot procedure, and amplified at three polymorphic loci. The double swab technique showed the highest percentage recovery of saliva from human skin among the three methods studied. This technique is suggested as an improvement over the classical single wet cotton swab technique.

Bites and Stings↗

PCR-based DNA typing of saliva stains recovered from human skin.

Human bites in cases of homicide, sexual assault, and abuse are often distorted due to the elasticity and curvature of the skin. Physical comparison of a bite mark to a suspect's teeth is sometimes difficult. Saliva, which is usually deposited during biting, can be collected and analyzed to identify the perpetrator. Using simulated bite mark situations in two experimental series, three samples of 40 microL of whole saliva were deposited on the skin of 27 cadavers (at 33 sites) and three samples of 100 microL of whole saliva were deposited on the skin of 5 cadavers (at 12 sites). Saliva was collected using the double swab technique at t = 5 min, t = 24 h, and t = 48 h. DNA was extracted using the modified Chelex method and submitted to PCR-based typing at two short tandem repeat loci. Results indicate that the concentration of DNA in saliva recovered from skin varies as a function of time since deposition. There is a significant decrease in concentration in the first 24 h but the concentration remains stable from 24 to 48 h. The success of PCR amplification is independent of the time since deposition or the concentration of DNA in the saliva sample. Contamination from the DNA of the cadaver was not found in any of the cases studied.

Bites, Human↗