APOA1 (-75 G>A and 83 C>T) and APOB (2488 C>T) polymorphisms and their association with myocardial infarction,lipids and apolipoproteins in patients with type 2 diabetes mellitus

IntroductionThe increased risk of myocardial infarction (MI) in type 2 diabetes mellitus (T2DM) is well documented. Polymorphisms in APOA1 and APOB genes allow us to identify new genetic markers in the Mexican population with T2DM and MI.Material and methodsWe studied 135 patients with DMT2 and MI (DI); another 85 non-infarcted diabetic individuals with DMT2 but without previous ischemic events (NID) and 242 healthy subjects (HS). All three groups were selected with the aim to investigate the association between the polymorphisms and infarction when T2DM is present or absent.Results-75 G>A polymorphism: Differences were found in genotype distribution between DI and NID individuals (OR = 2.01, 95% CI: 1.117–3.623, p = 0.019) with an increased risk for A in the dominant model (OR = 1.77, 95% CI: 1.020–3.084, p = 0.042); also concentrations of ApoA-I for A/A were lower in comparison with G/A (p = 0.038) and LDL-C and HDL-C levels were lower in G/A compared to G/G carriers. 83 C>T polymorphism of APOA1: For DI individuals, HDL-C was lower in T/T compared to C/C and triglyceride levels were lower in C/T compared to C/C carriers.ConclusionsThe -75 G>A APOA1 polymorphism could be considered as a susceptibility factor for myocardial infarction in individuals with T2DM and 2488 C>T APOB polymorphism is associated with changes in HDL-C and LDL-C and triglycerides in the same group.     

Hematopoietic stem cell transplantation (HSCT): an approach to autoimmunity

HSCT provides the opportunity to replace a damaged tissue. It is the most important treatment for high risk hematologic malignant and non malignant disorders. An important challenge in the identification of matched donors/patients is the HLA diversity. The Mexican Bone Marrow Registry (DONORMO) has nowadays > 5000 donors. The prevalent alleles are Amerindian, Mediterranean (Semitic and Spanish genes) and African. In theory, it is possible to find 11% of 6/6 A-B-DR low resolution matches for 70% of patients with Mexican ancestry. We contributed with 39 unrelated, cord blood and autologous HSCT for patients with malignant, genetic and autoimmune disorders. Overall disease survival was 50% (2-7 years) depending on the initial diagnosis, conditioning, disease evolution or other factors. Clinical studies using autologous and unrelated HSC are performed on patients with refractory autoimmune diseases producing mixed results: mainly, T1D, RA, MS, SLE. Improvement has been observed in skin damage and quality of life in SLE and systemic sclerosis. Disease stabilization in 2/3 of MS patients. However, in RA and T1D, initial benefits have been followed by eventual relapse. With growing clinical experience and protocol improvement, treatment-related mortality is decreasing. Proof efficacy will be achieved by comparing HSCT with standard therapy in autoimmunity.     

Glucose regulation of memory for reward reduction in young and aged rats

Although baseline blood glucose levels in aged Fischer-344 rats are comparable to those of young rats, the rise in blood glucose in response to training-related stress is substantially attenuated. The diminished response may contribute to increased depletion of extracellular brain glucose levels during training in aged rats; the depletion is blocked and memory is enhanced by systemic injections of glucose. The present experiment examined the role of glucose in regulating memory for reward reduction training. Blood glucose levels exhibited a significant rise after reward reduction trials in young adult but not 2-year-old rats. Although young and aged rats exhibited comparable learning during the day of reward reduction training, aged rats exhibited more rapid forgetting of the learning response. Post-training glucose injections (200 mg/kg, i.p.) facilitated memory formation and slowed the rate of forgetting in young and old rats, consistent with the view that deficiencies in circulating glucose responses to training may contribute to the rapid forgetting evident in aged Fischer-344 rats.     

Pretreatment with glycomacropeptide reduces allergen sensitization, alleviates immediate cutaneous hypersensitivity and protects from anaphylaxis

Allergic disorders are characterized by the involvement of allergen-specific immunoglobulin (Ig)E antibodies and T helper type 2 (Th2) cells. The search for new therapies for allergic diseases has been the primary focus of interest for many investigators in recent years. Glycomacropeptide (GMP) is a biologically active component of milk that exhibits a range of immunomodulatory functions. We examined whether oral administration of GMP could affect the development of allergic sensitization and the severity of immediate cutaneous hypersensitivity reactions and of anaphylaxis. Rats treated with or without GMP were ovalbumin (OVA)-sensitized and several indicators of allergy were evaluated. Pretreatment with GMP resulted in reduction of antigen-specific IgE titre in rats when sensitized with OVA. GMP administration also markedly suppressed the proliferative response of splenocytes to antigen and the production of interleukin (IL)-13 by splenocytes of sensitized animals. In addition, GMP pretreatment attenuated the intensity of the immediate cutaneous reaction induced by antigen and protected the sensitized rats from severe anaphylaxis. These data demonstrate, for the first time, that the administration of GMP prevents allergen sensitization and reduces the severity of the early-phase reaction induced by antigen in cutaneous hypersensitivity and in anaphylaxis. GMP may be used as a novel prophylactic agent for the control of allergic diseases.     

A novel method for DNA delivery into bacteria using cationic copolymers

Amphiphilic copolymers have a wide variety of medical and biotechnological applications, including DNA transfection in eukaryotic cells. Still, no polymer-primed transfection of prokaryotic cells has been described. The reversible addition-fragmentation chain transfer (RAFT) polymer synthesis technique and the reversible deactivation radical polymerization variants allow the design of polymers with well-controlled molar mass, morphology, and hydrophilicity/hydrophobicity ratios. RAFT was used to synthesize two amphiphilic copolymers containing different ratios of the amphiphilic poly[2-(dimethyl-amino) ethyl methacrylate] and the hydrophobic poly [methyl methacrylate]. These copolymers bound to pUC-19 DNA and successfully transfected non-competent Escherichia coli DH5α, with transformation efficiency in the range of 10³ colony-forming units per µg of plasmid DNA. These results demonstrate prokaryote transformation using polymers with controlled amphiphilic/hydrophobic ratios.     

Trophozoites of <Emphasis Type="Italic">Entamoeba histolytica</Emphasis> express a CD59-like molecule in human colon

In vitro studies have proved the presence of epitopes of CD59 in the surface of trophozoites of Entamoeba histolytica (E. histolytica). However, it has not been proved if CD59 molecules are expressed in the surface during the trophozoites’ tissue invasion. The aim of the present study was to determine whether the complement-regulatory protein CD59 is present on trophozoites of E. histolytica in human colon. Eleven specimens of amoebic colitis were studied by immunohistochemistry and electron microscopy techniques with a monoclonal antibody against human CD59 molecule. Our results show that a CD59-like molecule is expressed in trophozoites of E. histolytica found in colonic amebic lesions. Also, a CD59-like molecule was detected by western blot analysis in whole lysate of E. histolytica as well as on the plasma membrane by immunocytochemistry. These results suggest that E. histolytica can use CD59-like protein against the lytic action of membrane attack complex.     

Hyaline‐vascular type Castleman’s disease of the pararenal retroperitoneum: Multidetector CT findings

We describe the case of a 40‐year‐old woman who presented with a pararenal hyaline‐vascular type Castleman’s disease that had an arterial supply from the renal artery and a draining vein as showed by multidetector CT. Identification of the renal artery relationship to the feeding vessel of the mass is critical to prevent potential surgical complications.