Effect of advanced glycation end products on platelet activation and aggregation: a comparative study of the role of glyoxal and methylglyoxal.

Advanced glycation end products (AGEs) arising from dietary intake have been associated with numerous chronic diseases including cardiovascular diseases. The interaction between platelets and AGEs has been proposed to play a role in the etiology of cardiovascular diseases. However, the effects of the interaction between platelets and Maillard reaction products generated from glyoxal (Gly) or methylglyoxal (MG) are poorly understood. In this work, the effects of AGEs generated by the reaction between Gly or MG with Lys or bovine serum albumin (BSA) on platelet activation and aggregation were assessed. AGEs were generated incubating Gly or MG with Lys or BSA during 5 hours or 14 days, respectively. AGEs generation were characterized by kinetic studies and by amino acid analysis. Human platelet-rich plasma (PRP) was incubated with different concentrations of AGEs from Lys-MG or Lys-Gly and BSA-MG or BSA-Gly. Platelet activation was determined quantifying the expression of CD62 (P-selectin) in PRP exposed to different AGEs concentrations. It was found that Lys-MG and Lys-Gly induced an increase in P-selectin expression (p < .05), being 33.9% higher for Lys-MG when compared to Lys-Gly. Platelets incubated in the presence of BSA-MG and BSA-Gly did not show an increase in the P-selectin expression. Platelet aggregation was significantly higher for the mixture Lys-MG (in all the range of concentrations evaluated), whereas for Lys-Gly it was only significant the highest concentration (Lys 168 µM/Gly 168 µM). It was observed a significant increase in platelet aggregation induced by ADP for samples BSA-Gly. AGEs formed with MG-Lys induce a higher activation and aggregation of platelets when compared to those formed from Gly-Lys.

Comprehensive geriatric assessment in elderly patients with newly diagnosed aggressive non-Hodgkin lymphoma treated with multi-agent chemotherapy.

OBJECTIVES: The purpose of this prospective observational study is to evaluate the relation of the comprehensive geriatric assessment (CGA) to tolerability and survival of multi-agent chemotherapy for curative intent in elderly patients with aggressive non-Hodgkin lymphoma (NHL). MATERIALS AND METHODS: Patients who were 1) age ≥65 years, 2) newly diagnosed aggressive NHL, and 3) treated with multi-agent chemotherapy within 2 weeks from the time of diagnosis were enrolled from January 2011 to June 2014. Baseline clinical, laboratory, and CGA data being composed of Mini Nutritional Assessment-Short Form (MNA-SF), Korean version of Mini Mental Status Exam, Korean-Geriatric Depression Scale, and Groningen Frailty Index (GFI), were collected and analyzed for the relation to the outcome factors. RESULTS: Seventy patients were included; the median age was 73.5 years, 27 (38.6%) patients were Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 or more, and half of the patients were high or high-intermediate risk by age-adjusted international prognostic index (aaIPI). Most patients received CHOP or CHOP-like chemotherapy. Factors affecting discontinuation of chemotherapy within 12 weeks were poor MNA-SF, poor GFI, poor PS, and presence of B symptom. Among those, poor MNA-SF was independent of other variables in multivariate analysis. Poor MNA-SF, bone marrow involvement, and baseline anemia of hemoglobin<10g /dL were found to be independent factors associated with inferior overall survival whereas aaIPI factors were not. CONCLUSION: MNA-SF predicted tolerability to multi-agents chemotherapy and overall survival in elderly patients with aggressive NHL who were treated with multi-agent chemotherapy.

Experimental gluing of the bronchial stump after pneumonectomy in rats.

OBJECTIVE: The objective of this experimental study was to evaluate the usefulness of gelatin-resorcinol-dialdehyde adhesive in sutureless closure of bronchial stumps. METHODS: In 40 male Wistar rats bronchial stumps after left-sided pneumonectomy were closed by gluing with gelatin-resorcinol-dialdehyde adhesive. For macroscopic and microscopic examination four animals were sacrificed on postoperative days 2, 7 and 14 each, 14 animals on postoperative days 28 and 120 each. RESULTS: On macroscopic examination the gelatin-resorcinol-dialdehyde adhesive proved in all cases effective in tight bronchial stump closure. The adhesive did not cause local infection or necrosis of the bronchial stump nor other intrathoracic inflammatory complications. All animals survived and made an uncomplicated postoperative recovery. Microscopic examination revealed that the gelatin-resorcinol-dialdehyde adhesive initially evoked an acute inflammatory response with polymorphonuclear neutrophils predominating. After an intermediate stage characterized by a granulomatous reaction and resorption of the adhesive by multinucleated giant cells, 120 days postoperatively the bronchial stumps at the sites of previous gluing showed a regular fibrous scar tissue without inflammatory cells. CONCLUSION: The gelatin-resorcinol-dialdehyde adhesive showed effective in closing bronchial stumps after pneumonectomy in rats. The clinical extrapolation of this effect to thoracic surgical patients is uncertain at this time.

Experimental gluing of lung parenchyma in rats.

Gelatin-resorcinol-dialdehyde adhesive has been developed from a gelatin-resorcinol-formaldehyde adhesive by replacing the formaldehyde with two less histotoxic dialdehydes, ethandial and pentandial. The aim of the present study was to evaluate the usefulness of this modified composition in gluing defects in lung parenchyma. In 40 male Wistar rats a standardized lung incision 1.0 cm in length and 0.8 cm in depth were closed by application of gelatin-resorcinol-dialdehyde adhesive. For macroscopic and microscopic examination 4 animals were sacrificed on each of postoperative days 2, 7, and 14 and 14 animals on each of postoperative days 28 and 120. Macroscopic examination revealed a tight closure of the parenchymal defects in all postoperative stages. Initially by an adhesive layer and later on by granulation tissue and scar tissue respectively. On microscopic examination an inflammatory tissue response with polymorphonuclear neutrophils and macrophages predominating was found 2 days postoperatively. After 7 days multinucleated giant cells appeared. On postoperative day 14 the tissue response presented a distinct granulomatous character with multinucleated giant cells persisting. After 28 days remnants of adhesive surrounded by granulation tissue were detectable. On postoperative day 120 the adhesive had been completely resorbed and the parenchymal defect was replaced by fibrous scar tissue. The gelatin-resorcinol-adhesive proved effective in tight closure of lung parenchyma in rats. The adhesive is resorbed completely and does not interfere with parenchymal healing.

Formaldehyde-free collagen glue in experimental lung gluing.

Because of the well-known limitations of the adhesive strength of fibrin glue, it is imperative to develop a stronger glue with acceptable biocompatibility. This was accomplished by removing the formaldehyde component from gelatin-resorcinol-formaldehyde glue and replacing it by two less toxic aldehydes--pentanedial and ethanedial. To evaluate the adhesive strength of this new glue, GR-DIAL, lung incisions in rabbit hybrids were glued together. Each group (n = 5) was examined histologically after 2 days and 1, 2, and 4 weeks. The glue disintegrated gradually with good bioresorption when the incision was closed with a thin layer of glue. The healing process was favorable, indicating good biocompatibility. Therefore, GR-DIAL glue is capable of enhancing the use of surgical glues in the field of thoracic surgery by enabling surgeons to close larger parenchymal lesions than with fibrin glue.

Selection for high immunogenicity in drug-resistant sublines of murine lymphomas demonstrated by plaque assay.

The immunogenicity of lymphoma L1210 and three L1210 sublines, resistant to methylglyoxal bis(guanylhydrazone), 4,4'-diacetyldiphenylurea bis(guanylhydrazone), or guanazole (L1210/GZL), respectively, was evaluated. Syngeneic DBA/2J mice were given a single i.p. injection of serially diluted suspension of irradiated cells from L1210 or L1210 sublines. Five days later spleen cells from the immunized mice were tested for the presence of plaque-forming cells using the immunizing lymphoma cell lines as target. Sera collected from the animals were examined for cytolytic antibody activity by lysis in gel using the same target cells. For comparison, the H-2 immunogenicity of L1210 and its sublines was investigated in H-2-incompatible allogeneic mice. The following results were obtained. (a) All the sublines showed increased immunogenicity and susceptibility to lysis as compared to L1210 cells. The number of plaque-forming cells/spleen ranged from 100 for L1210 to 4450 for L1210/GZL, the most immunogenic subline, and the antibody titer ranged from 1/8 for L1210 to 1/128 for L1210/GZL. (b) All the sublines carried common tumor-associated antigens that apparently made primary contributions to the increased immunogenicity. (c) The common tumor-associated antigens were also expressed on L1210 cells, although in a lesser defree, as evidenced by the definite, albeit low, capacity of L1210 cells to absorb DBA/2J anti-L1210/GZL antibodies. (d) Spleen and thymus cells of DBA/2J mice as well as unrelated murine ascites tumor cells did not cause significant absorption of these antibodies. (e) Only a partial inverse relationship could be demonstrated between tumor-associated antigens but the lowest for H-2. The above results would seem compatible with the hypothesis that the increased immunogenicity of drug-resistant L1210 sublines is attributable to the selection of preexisting highly immunogenic cells during immunosuppression by treatments selecting for drug resistance.

Isolation of a bovine Theileria.

Dual infections of Anaplasma marginale and a Theileria, resembling Theileria mutans, occurred in splenectomized calves inoculated with pooled blood samples from eastern Texas cattle. Theileria was obtained in pure form by treating dually infected cattle with selectively eliminated Anaplasma. These theileria infections were responsible for mild, transient reductions in packed red blood cell volume (PCV).