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Biomedical subjects

L Pena

Publications and source records attributed to L Pena.

9 recordsLinked to original sources

Alpha-fibrinogenases.

Snake venoms contain a number of serine and metalloproteinases, included among these are the fibrinolytic metalloproteinases. When the fibrinolytic enzymes were first isolated from viper venoms it was postulated that there may be a clinical application for these enzymes in the treatment of occlusive thrombi, such as those occurring in the great arteries and veins of cardiac and cerebral circulation as well as peripheral arteries and veins. In the ensuing years a substantial body of literature has been generated on the identification and characterization of the fibrinolytic enzymes from a broad spectrum of snake species. In this report we describe the biological properties and positive clinical features of the class of enzymes known as alpha-fibrinogenases. Fibrolase, a fibrinolytic metalloproteinase originally isolated from Agkistrodon contortrix contortrix venom, is the representative fibrinolytic enzyme used for the description and characterization of the alpha-fibrinogenases in this chapter. The biochemical and physiochemical properties and in vivo activity of the enzyme are described as well as in vitro studies using a platelet avid chimera of fibrolase. The chimera was formed by coupling fibrolase to an Arg-Gly-Asp (RGD) like peptide imparting inhibitory activity on platelet aggregation and thrombus formation, while maintaining full fibrinolytic activity. Fibrolase has also been modified through the adduction of polyethylene glycol to reduce the rate of clearance from the circulation. In this review we also include a description of alfimeprase, a recombinant fibrinolytic enzyme derived from fibrolase, and follow the development of the enzyme as a potential clinical agent in the clearance of occlusive thrombi. Alfimeprase is presently in clinical trials for two indications: the treatment of peripheral arterial occlusions (in which phase II is nearing successful completion), and for use in the clearance of occluded vascular access catheters in direct competition with plasminogen activators.

Agkistrodon↗

Prevalence of malocclusion and orthodontic treatment need in children and adolescents in Bogota, Colombia. An epidemiological study related to different stages of dental development.

The aim of the study was to assess the prevalence of malocclusion in a population of Bogotanian children and adolescents in terms of different degrees of severity in relation to sex and specific stages of dental development, in order to evaluate the need for orthodontic treatment in this part of Colombia. A sample of 4724 children (5-17 years of age) was randomly selected from a population that attended the Dental Health Service; none had been orthodontically treated. Based on their dental stages the subjects were grouped into deciduous, early mixed, late mixed and permanent dentition. The registrations were performed according to a method by Björk et al. (1964). The need for orthodontic treatment was evaluated according to an index used by the Swedish National Board of Health. The results showed that 88 per cent of the subjects had some type of anomaly, from mild to severe, half of them recorded as occlusal anomalies, one-third as space discrepancies, and one-fifth as dental anomalies. No clear sex differences were noted, except for maxillary overjet, spacing, tooth size (all more frequent in boys), and crowding (more frequent in girls). Occlusal anomalies and space discrepancies varied in the different dental developmental periods, as did tipped and rotated teeth. Little need for orthodontic treatment was found in 35 per cent and moderate need in 30 per cent. A great need was estimated in 20 per cent, comprising children with prenormal occlusion, maxillary overjet, or overbite (> 6 mm), posterior unilateral crossbite with midline deviation (> 2 mm), severe crowding or spacing, congenitally missing maxillary incisors, impacted maxillary canines or anterior open bite (> 3 mm in the permanent dentition). Urgent need for treatment was estimated to be 3 per cent, comprising subjects with extreme post- and pre-normal occlusion, impacted maxillary incisors or extensive aplasia.

Adolescent↗

Changes in various plasma lipid components, glucose, and insulin in Spermophilus lateralis during hibernation.

This study evaluated fat mobilization as related to gluconeogenesis in two age groups of hibernating golden-mantled ground squirrels (Spermophilus lateralis). Our experimental group consisted of a total of 16 male and 15 female squirrels. Plasma samples were collected from selected animals being killed weekly from January to March, and the concentration of triglycerides, glycerol (GY), free fatty acids (FFA), total cholesterol, lipase activity, glucose, and insulin, were determined by biochemical assays and radioimmunoassay. Our results showed a mean FFA/GY ratio of five, which was higher than the predicted value of three, suggesting a significant depletion of GY and an enhanced rate of gluconeogenesis via GY to maintain glucose homeostasis in the hibernating animals. The factor of age did not significantly affect plasma lipid components. However, in the male group, plasma glucose levels were significantly higher for adults than for juveniles. Overall, females had significantly higher plasma glucose levels than males (150 +/- 11 vs. 110 +/- 8 mg%, P < 0.05). In the adult group, a gender influence was also seen on plasma insulin levels, with females' being higher than males' (66 +/- 13 vs. 25 +/- 3 microIU/ml, P < 0.01). We suggest that during hibernation, female squirrels may have a higher rate of lipolysis and gluconeogenesis along with a lower glucose utilization than their male counterparts. Additionally, adult females may exhibit a higher peripheral insulin resistance during hibernation than adult males, a possibility which merits further study.

Age Factors↗

Swine-reconstituted SCID mice as a model for African swine fever virus infection.

Injection of swine peripheral blood mononuclear cells into mice with severe combined immunodeficiency (SCID), resulted in the stable long-term establishment of a functional swine immune system (SCID-sw). Swine immunoglobulins were present in the serum of SCID-sw mice and swine cells were detected in the blood as well as in lymph nodes and spleen using monoclonal antibodies raised against cell subpopulations. Swine lymphocytes from reconstituted SCID mice responded in vitro to specific antigens or mitogens. When SCID-sw mice were challenged with African swine fever (ASF) virus, ASF virus-infected cells were detected in blood and spleen, and antiviral antibodies and virus-specific T cells were generated.

African Swine Fever Virus↗

African swine fever virus guanylyltransferase.

The gene coding for the guanylyltransferase of African swine fever virus has been identified and sequenced. The gene, designated NP868R, is located within fragments EcoRI N' and D of the virus genome (BA71V strain) and encodes a protein with a predicted molecular mass of 99.9 kDa that shares significant similarity with the large subunit of both vaccinia and Shope fibroma virus capping enzymes, with percentages of identity of 20.6 and 21.8%, respectively. A protein of 95 kDa was induced in Escherichia coli cells transformed with a recombinant plasmid carrying the NP868R gene. The E. coli expressed protein, as well as a protein of the same molecular weight present in African swine fever virus particles, form a covalent complex with GTP that can be reversed by pyrophosphate, two characteristic reactions of guanylyltransferases. An examination of the amino acid sequences of the African swine fever virus, poxvirus, and yeast guanylyltransferases has revealed a common motif around a lysine residue at the amino-terminal part of the proteins [Y(V, A)X2K(T, A)DG] which resembles the adenylylation site of DNA ligases (Tomkinson, A. E., Totty, N. F., Ginsburg, M., and Lindahl, T. (1991). Proc. Natl. Acad. Sci. USA 88, 400-404). This lysine residue could be the guanylylation site in these enzymes.

African Swine Fever Virus↗

Interferon-gamma production by African swine fever virus-specific lymphocytes.

Peripheral blood mononuclear cells (PBMC) from inbred pigs that were immunized with autologous macrophages infected with the African swine fever (ASF) virus BA71V, a nonvirulent virus isolate, proliferated and produced interleukin-2 in response to homologous and heterologous isolates of the ASF virus. They produced, however, interferon (IFN) only when challenged in vitro with homologous or attenuated isolates of the ASF virus, but not with heterologous or virulent isolates. The IFN was pH 2 labile and was neutralized by specific serum to porcine recombinant IFN gamma.

African Swine Fever↗

A protein of molar mass 12 kDa incorporates into the membrane of ASF virus-infected cells.

An African swine fever virus-induced protein of molar mass 12 kDa (p12) was studied in virus-infected Vero cells using the monoclonal antibody 18B.B11. Protein p12 is incorporated into the membrane of infected cells about 7 h post-infection and is not present in purified African swine fever virus particles. The synthesis of protein p12 is sensitive to cytosine arabinoside.

African Swine Fever Virus↗

Organs transplanted from intoxicated donors.

PURPOSE: The purpose of our study was to evaluate short- and long-term results of transplants from cadaver donors who have died of poisoning by various substances. MATERIALS AND METHODS: The actuarial survival rate of organs from intoxicated donors was calculated using the Kaplan-Meier method. RESULTS: Among the 507 donors between January 1998 and December 2002, 5 (0.98%) had a cause of brain death of poisoning, namely, organo-phosphates (n = 2), methanol (n = 1), cyanide (n = 1) and acetylsalicilic acid(n = 1), from whom were procured 10 kidneys, 1 liver, 2 corneas, and 1 set of bones. The follow up for patients receiving solid organs was 15.2 months (range, 0-48 months). At 3 months, 90% of kidneys had normal function. No delayed graft function rejection episodes or major complications were reported in any recipient. None showed evidence of acute or chronic poisoning. Two died, 1 early mortality was due to anesthetic complications and the other at 17 months to an unknown cause. Actuarial kidney survival rates were 90% and 80% at 12 and 24 months, respectively. The liver recipient was well at the end of follow up. CONCLUSION: Using organs of poisoned donors is feasible with comparable graft survival rates to other recipient.

Adolescent↗