Synthesis, characterization and stability of crosslinked chitosan-maltodextrin pH-sensitive nanogels.

Polysaccharide-based nanogels offer a wide range of chemical compositions and are of great interest due to their biodegradability, biocompatibility, non-toxicity, and their ability to display pH, temperature, or enzymatic response. In this work, we synthesized monodisperse and tunable pH-sensitive nanogels by crosslinking, through reductive amination, chitosan and partially oxidized maltodextrins, by keeping the concentration of chitosan around the overlap concentration, i.e. in the dilute and semi-dilute regime. The chitosan/maltodextrin nanogels presented sizes ranging from 63 ±â€¯9 to 279 ±â€¯16 nm, showed quasi-spherical and cauliflower-like morphology, reached a ζ-potential of +36 ±â€¯2 mV and maintained a colloidal stability for up to 7 weeks. It was found that the size and surface charge of nanogels depended both on the oxidation degree of maltodextrins and chitosan concentration, as well as on its degree of acetylation and protonation, the latter tuned by pH. The pH-responsiveness of the nanogels was evidenced by an increased size, owed to swelling, and ζ-potential when pH was lowered. Finally, maltodextrin-chitosan biocompatible nanogels were assessed by cell viability assay performed using the HEK293T cell line.

Lignocellulosic Membranes Grafted with N-Vinylcaprolactam Using Radiation Chemistry: Load and Release Capacity of Vancomycin.

Radiation chemistry presents a unique avenue for developing innovative polymeric materials with desirable properties, eliminating the need for chemical initiators, which can be potentially detrimental, especially in sensitive sectors like medicine. In this investigation, we employed a radiation-induced graft polymerization process with N-vinylcaprolactam (NVCL) to modify lignocellulosic membranes derived from Agave salmiana, commonly known as maguey. The membranes underwent thorough characterization employing diverse techniques, including contact angle measurement, degree of swelling, scanning electron microscopy (SEM), atomic force microscopy (AFM), Fourier-transform infrared-attenuated total reflectance spectroscopy (FTIR-ATR), nuclear magnetic resonance (CP-MAS 13C-NMR), X-ray photoelectron spectroscopy (XPS), and uniaxial tensile mechanical tests. The membranes' ability to load and release an antimicrobial glycopeptide drug was assessed, revealing significant enhancements in both drug loading and sustained release. The grafting of PNVCL contributed to prolonged sustained release by decreasing the drug release rate at temperatures above the LCST. The release profiles were analyzed using the Higuchi, Peppas-Sahlin, and Korsmeyer-Peppas models, suggesting a Fickian transport mechanism as indicated by the Korsmeyer-Peppas model.

Removal of Arsenate by Fixed-Bed Columns Using Chitosan-Magnetite Hydrogel Beads and Chitosan Hydrogel Beads: Effect of the Operating Conditions on Column Efficiency.

Fixed-bed columns packed with chitosan-magnetite (ChM) hydrogel and chitosan (Ch) hydrogel were used for the removal of arsenate ions from aqueous solutions at a pH of 7.0. The effect of flow rate (13, 20, and 25 mL/h), height of the columns (13 and 33 cm), and initial arsenate concentration (2, 5 and 10 mg/L) on the column's efficiency for the removal of As(V) is reported. The maximum adsorption capacity (qb), obtained before the allowed concentration of contaminant is exceeded, the adsorption capacity (qe) when the column is exhausted, and the mass transfer zone were determined. With this information, the efficiency of the column was calculated, which is given by the HL/HLUB ratio. The higher this ratio, the higher the efficiency of the column. The highest efficiency and the highest uptake capacity value at breakthrough point were obtained when using the lower flow rate, lower initial arsenate concentration, and longer bed length. When 33 cm-high columns were fed with a 10 mg As(V)/L solution at 13 mL/h, the maximum uptake capacity values at exhaustion obtained for Ch and ChM were 1.24 and 3.84 mg/g, respectively. A pH increase of the solution at the column's exit was observed and is attributed to the proton transfer from the aqueous solution to the amino and hydroxyl groups of chitosan. The incorporation of magnetite into Ch hydrogels significantly increases their capacity to remove As(V) due to the formation of complexes between arsenic and the magnetite surface. Experimental data were fitted to the Thomas model, the Yoon-Nelson model and the Bohart-Adams model using non-linear regression analysis.

Pluronic F127 and P104 Polymeric Micelles as Efficient Nanocarriers for Loading and Release of Single and Dual Antineoplastic Drugs.

The potential application of biodegradable and biocompatible polymeric micelles formed by Pluronic F127 and P104 as nanocarriers of the antineoplastic drugs docetaxel (DOCE) and doxorubicin (DOXO) is presented in this work. The release profile was carried out under sink conditions at 37 °C and analyzed using the Higuchi, Korsmeyer-Peppas, and Peppas-Sahlin diffusion models. The cell viability of HeLa cells was evaluated using the proliferation cell counting kit CCK-8 assay. The formed polymeric micelles solubilized significant amounts of DOCE and DOXO, and released them in a sustained manner for 48 h, with a release profile composed of an initial rapid release within the first 12 h followed by a much slower phase the end of the experiments. In addition, the release was faster under acidic conditions. The model that best fit the experimental data was the Korsmeyer-Peppas one and denoted a drug release dominated by Fickian diffusion. When HeLa cells were exposed for 48 h to DOXO and DOCE drugs loaded inside P104 and F127 micelles, they showed lower IC50 values than those reported by other researchers using polymeric nanoparticles, dendrimers or liposomes as alternative carriers, indicating that a lower drug concentration is needed to decrease cell viability by 50%.

Arsenate Removal from Aqueous Media Using Chitosan-Magnetite Hydrogel by Batch and Fixed-Bed Columns.

The removal of arsenate ions from aqueous solutions at near-neutral pH was carried out using chitosan-magnetite (ChM) hydrogel beads in batch systems. Equilibrium isotherms and kinetic studies are reported. Obtained equilibrium and kinetic data were fitted to mathematical models, estimating model parameters by non-linear regression analysis. Langmuir model was found to best fit equilibrium data; a maximum adsorption capacity of 66.9 mg As/g was estimated at pH 7.0. Pseudo-first order kinetic model was observed to best fit kinetic data. The pH of the solution was observed to increase with increasing contact time, which is attributed to protonation of amine groups present in the hydrogel. Protonation of functional groups in the ChM sorbent yields a higher number of active sites for arsenate removal, being as this a process that can't be overlooked in future applications of ChM hydrogel for the removal or arsenate ions. Chitosan-magnetite and ChM-arsenate interactions were determined by XPS. Arsenate removal using fixed-bed column packed with ChM was carried out, reporting a non-ideal behavior attributed to pH increase of the effluent caused by proton transfer to ChM hydrogels.

Drug Delivery from Stimuli-Responsive Poly(N-isopropylacrylamide-co-N-isopropylmethacrylamide)/Chitosan Core/Shell Nanohydrogels.

The synthesis of stimulus-responsive poly(N-isopropylacrylamide-co-N-isopropylmethacrylamide)/chitosan core/shell nanohydrogels made by batch emulsion polymerization in the presence of chitosan (CS) micelles is reported. The ratio of monomers required to obtain copolymers with a volume phase transition temperature (TVPT) in the range of the temperatures observed in the human body in response to an infection (38 to 40 °C) was estimated with the Fox equation. The conversion was determined by gravimetry; mean particle size, size distribution, and thermal response were measured by quasi-elastic light scattering (QLS). The core/shell structure was confirmed by TEM, and FTIR showed the presence of N-isopropyl acrilamide (NIPA), N-isopropyl methacrylamide (NIPMA), and CS in the nanohydrogels. The nanohydrogels were loaded with the drug doxycycline hyclate, and their release kinetic profile was determined at pH = 2.0 and 7.4 at their volume phase transition temperatures (TVPT). A higher amount of drug was released at acidic pH. Some mathematical models described in the literature were used to fit the experimental drug release data.

Silver Nanoparticles Loaded on Polyethylene Terephthalate Films Grafted with Chitosan.

Currently, polyethylene terephthalate (PET) is one of the most widely used polymeric materials in different sectors such as medicine, engineering, and food, among others, due to its benefits, including biocompatibility, mechanical resistance, and tolerance to chemicals and/or abrasion. However, despite all these excellent characteristics, it is not capable of preventing the proliferation of microorganisms on its surface. Therefore, providing this property to PET remains a difficult challenge. Fortunately, different strategies can be applied to remove microorganisms from the PET surface. In this work, the surface of the PET film was functionalized with amino groups and later with a dicarboxylic acid, allowing a grafting reaction with chitosan chains. Finally, the chitosan coating was loaded with silver nanoparticles with an average size of 130 ± 37 nm, presenting these materials with an average cell viability of 80%. The characterization of these new PET-based materials showed considerable changes in surface morphology as well as increased surface hydrophilicity without significantly affecting their mechanical properties. In general, the implemented method can open an alternative pathway to design new PET-based materials due to its good cell viability with possible bacteriostatic activity due to the biocidal properties of silver nanoparticles and chitosan.

Removal of Cu(II) by Fixed-Bed Columns Using Alg-Ch and Alg-ChS Hydrogel Beads: Effect of Operating Conditions on the Mass Transfer Zone.

The removal of Cu(II) ions from aqueous solutions at a pH of 5.0 was carried out using fixed-bed columns packed with alginate-chitosan (Alg-Ch) or alginate-chitosan sulfate (Alg-ChS) hydrogel beads. The effect of the initial Cu(II) concentration, flow rate, pH, and height of the column on the amount of Cu removed by the column at the breakpoint and at the exhaustion point is reported. The pH of the solution at the column's exit was initially higher than that at the entrance, and then decreased slowly. This pH increase was attributed to proton transfer from the aqueous solution to the amino and COO- groups of the hydrogel. The effect of operating conditions on the mass transfer zone (MTZ) and the length of the unused bed (HLUB) is reported. At the lower flow rate and lower Cu(II) concentration used, the MTZ was completely developed and the column operated efficiently; by increasing column height, the MTZ has a better opportunity to develop fully. Experimental data were fitted to the fixed-bed Thomas model using a non-linear regression analysis and a good correspondence between experimental and Thomas model curves was observed.

Morphological and Mechanical Properties of Bilayers Wood-Plastic Composites and Foams Obtained by Rotational Molding.

In this work, the suitability for the production of sustainable and lightweight materials with specific mechanical properties and potentially lower costs was studied. Agave fiber (AF), an agro-industrial waste, was used as a reinforcement and azodicarbonamide (ACA) as a chemical blowing agent (CBA) in the production of bilayer materials via rotational molding. The external layer was a composite of linear medium density polyethylene (LMDPE) with different AF contents (0-15 wt %), while the internal layer was foamed LMDPE (using 0-0.75 wt % ACA). The samples were characterized in terms of thermal, morphological and mechanical properties to obtain a complete understanding of the structure-properties relationships. Increases in the thicknesses of the parts (up to 127%) and a bulk density reduction were obtained by using ACA (0.75 wt %) and AF (15 wt %). Further, the addition of AF increased the tensile (23%) and flexural (29%) moduli compared to the neat LMDPE, but when ACA was used, lower values (75% and 56% for the tensile and flexural moduli, respectively) were obtained. Based on these results, a balance between mechanical properties and lightweight can be achieved by selecting the AF and ACA contents, as well as the performance and aesthetics properties of the rotomolded parts.

Development, Characterization and In Vitro Biological Properties of Scaffolds Fabricated From Calcium Phosphate Nanoparticles.

Ceramic materials mimic the mineral composition of native bone and feature osteoconductive properties; they are therefore used to regenerate bone tissue. Much research focuses on increasing the porosity and pore interconnectivity of ceramic scaffolds to increase osteoconductivity, cell migration and cell-cell interaction. We aimed to fabricate biocompatible 3D-scaffolds featuring macro- and microporous calcium phosphates with high pore interconnection. Nanoparticles of hydroxyapatite (HA) and calcium deficient hydroxyapatite (CDHA) were synthesized by wet chemical precipitation. Scaffolds were produced from them by the replication polymeric foam technique. Solid content and sintering temperature were varied. Nanoparticles and scaffolds were characterized regarding morphology, chemical and mineral composition, porosity and mechanical properties. Biocompatibility, cell attachment and distribution were evaluated in vitro with human adipose mesenchymal stem cells. Scaffolds with total porosity of 71%-87%, pores in the range of 280-550 µm and connectivity density up to 43 mm-3 were obtained. Smaller pore sizes were obtained at higher sintering temperature. High solid content resulted in a decrease of total porosity but increased interconnectivity. Scaffolds 50HA/50ß-TCP featured superior interconnectivity and mechanical properties. They were bioactive and biocompatible. High HA solid content (40 wt.%) in the HA pure scaffolds was negative for cell viability and proliferation, while in the 50HA/50ß-TCP composite scaffolds it resulted more biocompatible.

Antibacterial effect of acrylic bone cements loaded with drugs of different action's mechanism.

INTRODUCTION: Antibiotic-loaded bone cements of poly(methyl methacrylate) are considered as very useful biomaterials for the management of corporal deep osseous infections. However, the high prevalence of resistant germs and polymicrobial infections makes it necessary to search for new formulations of bone cements containing antibiotics for local antibacterial therapy. In this work, bone cements loaded with drugs with different mechanism of action were evaluated to determine its antibacterial effectiveness on Pseudomonas aeruginosa. METHODOLOGY: Poly(methyl methacrylate) cements loaded with 10 wt.% of Oleozon®, mixtures of Ciprofloxacin/Meropenem and Ciprofloxacin/Meropenem/Oleozon® were prepared. The in vitro drugs release in water was followed by UV-Vis spectroscopy, and their antibacterial activity against Pseudomonas aeruginosa was evaluated for 11 days using the microdilution method. RESULTS: All the extracts demonstrated an inhibitory effect on the growth of the strain during the whole trial period. Extracts from cement with Oleozon® only presented a total antibacterial inhibitory effect during 20 hours for the extracts taken at day 1 while the extracts from the cements loaded with mixtures of Ciprofloxacin/Meropenem and Ciprofloxacin/Meropenem/Oleozon® showed complete inhibition of the growth of the microorganism, even at 11 days. At the end of the trial period, some of the drugs remained inside the matrices, indicating that they can be released for a longer time in treatments. CONCLUSIONS: The results indicated a positive antibacterial effect by the combined used of the two or the three drugs tested against the Gram-negative bacilli Pseudomonas aeruginosa, so these proposal may be a valid alternative to be considered by surgeons.

Effect of monomer dosing rate in the preparation of mesoporous polystyrene nanoparticles by semicontinuous heterophase polymerization.

The semicontinuous heterophase polymerization of styrene in the presence of cross-linking and porogen agents was carried out. Latexes with close to 20% solid content, which contained mesoporous nanoparticles with 28 nm in average diameters, up to 0.5 cm3/g in porosity and 6-8 nm in pore diameters were obtained. By varying the monomer dosing rate over the micellar solution, an unexpected direct dependence of instantaneous conversion on the monomer dosing rate was found. This was ascribed to the higher average number of radicals per particle attained in the polymerization at the higher dosing rate, which in turn would arise from the higher gel percentage in the polymer. It is believed that the cross-linked chains prevent encounters between radicals, delaying the bimolecular termination reactions and allowing the existence of more than one radical inside the particles, which in turn increases the propagation rate.

[National guidelines of diagnosis and treatment of the non-Hodgkin lymphoma]. / Guías nacionales de diagnóstico y tratamiento de linfoma no Hodgkin.

Non-Hodgkin lymphoma comprises a heterogeneous group of haematological malignancies, classified according to their clinic, anatomic-pathological features and, lately, to their molecular biomarkers. Despite the therapeutic advances, nearly half of the patients will die because of this disease. The new diagnostic tools have been the cornerstone to design recent therapy targets, which must be included in the current treatment guidelines of this sort of neoplasms by means of clinical trials and evidence-based medicine. In the face of poor diagnoses devices in most of the Mexican hospitals, we recommend the present diagnose stratification, and treatment guidelines for non-Hodgkin lymphoma, based on evidence. They include the latest and most innovative therapeutic approaches, as well as specific recommendations for hospitals with limited framework and therapy resources.

Size matters: smart copolymeric nanohydrogels: synthesis and applications.

In this work the synthesis of smart nanoparticles capable of respond to external stimulus (pH and temperature variations) is reported. To avoid post-polymerization modification, functionalized monomers able to respond to pH and temperature changes were and then polymerized. The synthesized monomers have the capability for coupling with folic acid which is the target molecule. For this reason their polymers can be used as targeted drug delivery systems. Smart polymeric nanoparticles were prepared by direct and inverse microemulsion polymerization of the synthesized monomers. The nanoparticles were charged with drugs and their release kinetic was studied.

Specific interactions study in complexes of poly(mono-n-alkyl itaconates) with tertiary polyamides.

This paper reports an FT-IR study of blends of poly(mono-n-alkyl itaconates) with poly(N,N-dimethylacrylamide) (PDMA) and poly(ethyloxazoline) (PEOX). Strong hydrogen bonding has been found, and both polybases have shown similar acceptor strengths. Derivative techniques show asymmetric profiles for the free carbonyl band of the polybases, resulting in shifted band locations. The extent of the interassociation has been estimated by spectral curve fitting of the polybase carbonyl band. The results show that the interaction degree in blends with PEOX does not depend on the length of the poly(monoalkyl itaconate) side group, while an inter-associating ability loss is observed in blends with PDMA as the side-group size of the polyacid increases. This different behavior is attributed to the greater interspacing between vicinal carbonyl groups in PEOX. This band shows conformational sensitivity and reflects the conformational changes that occur as the steric hindrances present in the medium (due to the bulky side groups of the polyacids) increase.

A critical review of the prognostic value of the nutritional status at diagnosis in the outcome of therapy of children with acute lymphoblastic leukemia.

The impact of undernutrition in the outcome of treatment of children with ALL has been analyzed by several authors who have highlighted undernutrition as another relevant prognostic factor in children with acute lymphoblastic leukemia (ALL). There are, however, some papers which have not confirmed the prognostic value of malnutrition at diagnosis in children with ALL. Overall, data from 1,123 children with ALL worldwide support the concept of malnutrition at diagnosis being useful as a prognostic factor, whereas data from 1,271 children fail to support this concept. We here critically analyze the information of these publications referring to a total of 2,394 children with ALL. Detailed information was available only from 500 of the 2,394 patients, stemming from six publications; of these individuals, at diagnosis, 376 were well nourished and 124 were malnourished. In this subset of patients, the analysis of the data shows that the 5-year (or longer) overall survival of undernourished children (UNC) was 26%, whereas that of well-nourished children (WNC) was 59% (p < 0.001); along the same line the relative risk of dying during this period was 1.8 times higher for UNC than WNC (p < 0.01; Interval of Confidence [IC] 95%: 1.72-1.88). On the other hand, the censoring time of these 500 children is different: 293 were censored at 5 years after diagnosis, whereas 207 where censored at 8-10 years: The overall survival for each of these periods was also different: 36% versus 2% for UNC (p < 0.001), and 56% versus 63% (p > 0.10) for WNC, data which support the concept that the differences in survival are more apparent in UNC if the period of observation is extended. These data suggest that undernutrition at diagnosis by itself and without interacting with other variables, may be a significant prognostic factor in the long-term outcome of treatment of pediatric patients with ALL. After identifying these variables as important, imaginative approaches to the treatment of cancer in childhood in the years ahead may lead into the improvement of the results of these treatments.

An addition to geographic hematology: chronic myeloproliferative diseases are infrequent in Mexican Mestizos.

BACKGROUND: The chronic myeloproliferative diseases (CMPDs) include chronic myelogenous leukemia (CML), primary (essential) thrombocythemia (PT), agnogenic myeloid metaplasia (AMM), and polycythemia vera (PV). Certain hematological malignancies have a different prevalence in our country than in countries with Caucasian populations. Data indicate that the prevalence of CML in our country is similar to that found in Caucasians; however, the prevalence of the other CMPDs has not been studied. METHODS: In a total of 8069 individuals studied between June 1983 and March 2001 in the Centro de Hematologia y Medicina Interna de Puebla, we assessed the prevalence of CML, PT, AMM, and PV. Some of the clinical features of these individuals were also assessed. RESULTS AND CONCLUSIONS: Forty-nine patients with CML, 14 with PT, 7 with AMM, and 3 with PV were identified. The clinical presentations of these CMPDs were not different from those described in Caucasians. CONCLUSIONS: We found that CML was more than 3 times more frequent than PT, that both PV and AMM were exceptional, and that PT, AMM, and PV were significantly less frequent in Mexican than in Caucasian populations (P < .01).

Trombofilia, tromboembolia y el uso de las heparinas no fraccionadas y de bajo peso molecular / Thrombophilia, thromboembolism and the user of the unfractionated and low-molecular-weight hepatins

Se hace una revisión sobre los puntos sobresalientes en relación con la detección de los estados trombofílicos, el establecimiento de factores de riesgo para el desarrollo de trombosis, el diagnóstico de los estados tromboembólicos y un análisis sobre la experiencia en el uso de heparina no fraccionada y heparinas de bajo peso molecular. La enfermedad vasooclusiva es multifactorial y su manejo debe ser inter y multidisciplinario, para realizar un diagnóstico oportuno e instalar la profilaxis o el tratamiento antitrombótico adecuado. Aún cuando, utilizando heparinas de bajo peso molecular se observan ventajas importantes en cuanto a la respuesta terapéutica, la heparina no fraccionada mantiene sus indicaciones específicas y en muchas ocasiones, ambas heparinas son complementarias para un mejor tratamiento de la tromboembolia. Consideramos que cada unidad médica debe establecer sus propios criterios y algoritmos diagnósticos y terapéuticos que permitan detectar, diagnosticar y tratar la trombosis en forma oportuna y disminuir la morbimortalidad por esta causa.

Bacterias en el citoplasma de leucocitos de pacientes inmunocomprometidos: un hallazgo citológico poco frecuente. A propósito de dos casos / Bacteria in the cytoplasm of leukocytes of immunocompromised patients: an uncommon cytological finding. A report of two cases

Se comunican los aspectos clínicos y citológicos de dos pacientes con compromiso inmunológico: una mujer con lupus eritematoso generalizado y un niño con leucemia aguda linfoblástica, quienes recibieron tratamiento inmunosupresor y citotóxico. En los dos casos se observaron bacterias en el citoplasma de los leucocitos (Escherichia coli, Staphylococcus y Streptococcus pneumoniae), hallazgo poco frecuente que puede ser útil para establecer tratamientos oportunos y disminuir la morbilidad y la mortalidad. Se revisan también, brevemente, los efectos de los padecimientos y los tratamientos inmunosupresores. La observación de bacterias intraleucocitarias no es común, por lo cual requiere una adecuada capacitación en citología hematológica y un examen minucioso de las preparaciones rutinarias para las cuentas celulares de la citometría hemática.

Linfoma centrofacial: un análisis retrospectivo, clínico, patologíco y terapeutico de 10 casos / Centrofacial linfoma: a therapeutic pathological clinical retrospective analysis of ten cases

Se comunican 10 casos de linfoma centrofacial estudiados de manera retrospectiva entre 1995 y 1999, que correspondieron a 6.6 por ciento de todos los linfomas diagnosticasos durante este periodo; cuatro de los 10 pacientes fueron del sexo masculino, con mediana de edad de 59 años 89 a 87 años). En dos pacientes se localizó en el paladar, en dos se afectaron antro nasal y senos paranasales, En otros dos casos se afectaron paladar y nariz, y en dos más al maxilar; uno se localizó en el párpado y el tabique nasal y otro en el paladar y la amígdala derecha. Todos se mostraron como lesiones expansivas, mayores de 4 cm de diámetro (4.5 a 7 cm). Histopatológicamente, tres fueron de alto grado de malignidad (angiocéntricos) y siete de grado intermedio. En un caso se relacionó con infección por VIH. Según su estadio clínico al momento del diagnóstico, siete fueron estadio I; dos estadio II y uno estadio IV por infiltración asintomática de médula ósea. Todos recibieron quimioterapia combinada con ciclofosfamida, doxorrubicina, vincristina y prednisona cada 21 a 28 días, durante seis ciclos. Se logró respuesta completa en cuatro de los pacientes, respuesta parcial en dos y no hubo respuesta en cuatro enfermos. Fallecieron cuatro pacientes: dos por infección grave uno por actividad tumoral y uno por toxicidad a quimioterapia. La supervivencia libre de enfermedad es de 39 por ciento y la supervivencia total de 56 por ciento a 36 meses. Nuestros resultados terapéuticos son similares a lo informado en la literatura; consideramos que ante un linforma centrofacial es obligado realizar fenotipo inmunológico de las células linfomatosas y análisis exhaustivos para detectar genoma de virus linfotrópicos en el tejido tumoral, en virtud de sus implicaciones pronósticas, y un mayor número de estudios prospectivos y controlados que permitan conocer las características clínicas, inmunofenotípicas y de asociación con infecciones virales en pacientes mestizos mexicanos y establecer el mejor esquema terapéutico para las particularidades de nuestro país