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1.  Biodegradable Salicylate-Based Poly(anhydride-ester) Microspheres For Controlled Insulin Delivery 
Salicylate-based poly(anhydride-esters) (PAEs) chemically incorporate salicylic acid (SA) into the polymer backbone, which is then delivered in a controlled manner upon polymer hydrolysis. In this work, a salicylate-based PAE is a carrier to encapsulate and deliver insulin. Polymer microspheres were formulated using a water/oil/water double-emulsion solvent evaporation technique. The microspheres obtained had a smooth surface, high protein encapsulation efficiency, and relatively low emulsifier content. Insulin was released in vitro for 15 days, with no signs of aggregation or unfolding of the secondary structure. The released insulin also retained bioactivity in vitro. Concurrently, SA was released from the microspheres with polymer degradation and anti-inflammatory activity was observed. Based upon these results, the formulated microspheres enable simultaneous delivery of insulin and SA, both retaining bioactivity following processing.
PMCID: PMC3952025  PMID: 24027012
poly(anhydride-esters); microspheres; controlled release; insulin; salicylic acid
2.  Intestinal parasites and genotyping of Giardia duodenalis in children: first report of genotype B in isolates from human clinical samples in Mexico 
Memórias do Instituto Oswaldo Cruz  2014;109(3):388-390.
Giardia duodenalis is one of the most prevalent enteroparasites in children. This parasite produces several clinical manifestations. The aim of this study was to determine the prevalence of genotypes of G. duodenalis causing infection in a region of southeastern Mexico. G. duodenalis cysts were isolated (33/429) from stool samples of children and molecular genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, targeting the triosephosphate isomerase ( tpi ) and glutamate dehydrogenase ( gdh ) genes. The tpi gene was amplified in all of the cyst samples, either for assemblage A (27 samples) or assemblage B (6 samples). RFLP analysis classified the 27 tpi -A amplicons in assemblage A, subgenotype I. Samples classified as assemblage B were further analysed using PCR-RFLP of the gdh gene and identified as assemblage B, subgenotype III. To our knowledge, this is the first report of assemblage B of G. duodenalis in human clinical samples from Mexico.
PMCID: PMC4131797  PMID: 24676655
Giardia duodenalis; genotyping; PCR-RFLP; tpi - gdh; enteroparasites
3.  PolyMorphine: an innovative biodegradable polymer drug for extended pain relief 
Morphine, a potent narcotic analgesic used for the treatment of acute and chronic pain, was chemically incorporated into a poly(anhydride-ester) backbone. The polymer termed “PolyMorphine”, was designed to degrade hydrolytically releasing morphine in a controlled manner to ultimately provide analgesia for an extended time period. PolyMorphine was synthesized via melt-condensation polymerization and its structure was characterized using proton and carbon nuclear magnetic resonance spectroscopies, and infrared spectroscopy. The weight-average molecular weight and the thermal properties were determined. The hydrolytic degradation pathway of the polymer was determined by in vitro studies, showing that free morphine is released. In vitro cytocompatibility studies demonstrated that PolyMorphine is non-cytotoxic towards fibroblasts. In vivo studies using mice showed that PolyMorphine provides analgesia for 3 days, 20 times the analgesic window of free morphine. The animals retained full responsiveness to morphine after being subjected to an acute morphine challenge.
PMCID: PMC3455147  PMID: 22877734
morphine; biodegradable; polymer; extended release; pain treatment; prodrug
4.  Microscale Plasma-Initiated Patterning of Electrospun Polymer Scaffolds 
Microscale plasma-initiated patterning (μPIP) is a novel micropatterning technique used to create biomolecular micropatterns on polymer surfaces. The patterning method uses a polydimethylsiloxane (PDMS) stamp to selectively protect regions of an underlying substrate from oxygen plasma treatment resulting in hydrophobic and hydrophilic regions. Preferential adsorption of the biomolecules onto either the plasma-exposed (hydrophilic) or plasma-protected (hydrophobic) regions leads to the biomolecular micropatterns. In the current work, laminin-1 was applied to an electrospun polyamide nanofibrillar matrix following plasma treatment. Radial glial clones (neural precursors) selectively adhered to these patterned matrices following the contours of proteins on the surface. This work demonstrates that textured surfaces, such as nanofibrillar scaffolds, can be micropatterned to provide external chemical cues for cellular organization.
PMCID: PMC3062666  PMID: 21345656
Extracellular matrix; micropatterning; nanofibers; laminin-1; glial cells; nerve regeneration
5.  Salicylic acid-derived poly(anhydride-ester) electrospun fibers designed for regenerating the peripheral nervous system 
Continuous biomaterial advances and the regenerating potential of the adult human peripheral nervous system offer great promise for restoring full function to innervated tissue following traumatic injury via synthetic nerve guidance conduits. To most effectively facilitate nerve regeneration, a tissue engineering scaffold within a conduit must be similar to the linear microenvironment of the healthy nerve. To mimic the native nerve structure, aligned poly(lactic-co-glycolic acid)/bioactive polyanhydride fibrous substrates were fabricated through optimized electrospinning parameters with diameters of 600 ± 200 nm. Scanning electron microscopy images show fibers with a high degree of alignment. Schwann cells and dissociated rat dorsal root ganglia demonstrated elongated and healthy proliferation in a direction parallel to orientated electrospun fibers with significantly longer Schwann cell process length and neurite outgrowth when compared to randomly orientated fibers. Results suggest that an aligned polyanhydride fiber mat holds tremendous promise as a supplement scaffold for the interior of a degradable polymer nerve guidance conduit. Bioactive salicylic acid based polyanhydride fibers are not limited to nerve regeneration and offer exciting promise for a wide variety of biomedical applications.
PMCID: PMC3096072  PMID: 21442724
Nerve regeneration; electrospinning; fibers; polyanhydride; salicylic acid
6.  The Lupus Family Registry and Repository 
Rheumatology (Oxford, England)  2010;50(1):47-59.
The Lupus Family Registry and Repository (LFRR) was established with the goal of assembling and distributing materials and data from families with one or more living members diagnosed with SLE, in order to address SLE genetics. In the present article, we describe the problems and solutions of the registry design and biometric data gathering; the protocols implemented to guarantee data quality and protection of participant privacy and consent; and the establishment of a local and international network of collaborators. At the same time, we illustrate how the LFRR has enabled progress in lupus genetics research, answering old scientific questions while laying out new challenges in the elucidation of the biologic mechanisms that underlie disease pathogenesis. Trained staff ascertain SLE cases, unaffected family members and population-based controls, proceeding in compliance with the relevant laws and standards; participant consent and privacy are central to the LFRR’s effort. Data, DNA, serum, plasma, peripheral blood and transformed B-cell lines are collected and stored, and subject to strict quality control and safety measures. Coded data and materials derived from the registry are available for approved scientific users. The LFRR has contributed to the discovery of most of the 37 genetic associations now known to contribute to lupus through 104 publications. The LFRR contains 2618 lupus cases from 1954 pedigrees that are being studied by 76 approved users and their collaborators. The registry includes difficult to obtain populations, such as multiplex pedigrees, minority patients and affected males, and constitutes the largest collection of lupus pedigrees in the world. The LFRR is a useful resource for the discovery and characterization of genetic associations in SLE.
PMCID: PMC3307518  PMID: 20864496
Systemic lupus erythematosus; Registry; Repository; Autoimmune diseases; Genetics; Heritability; Genome-wide association studies; Linkage analysis; Minorities; Women
7.  Antibody-Based Detection Tests for the Diagnosis of Helicobacter pylori Infection in Children: A Meta-Analysis 
PLoS ONE  2008;3(11):e3751.
Numerous serologic tests are available for the diagnosis of H. pylori infection in children. Common designs of antibody-based detection tests are ELISA and Western Blot (WB). For developing countries with limited laboratory resources and access, ELISA would be the preferred method because of its simplicity, lower cost and speed. Although in adults ELISA has proven to be highly accurate in diagnosing H. pylori infection; in children, it has shown variable accuracy.
We conducted a systematic review and meta-analysis to assess the accuracy of antibody-based detection tests for the diagnosis of H. pylori infection in children. Selection criteria included participation of at least 30 children and the use of a gold standard for H. pylori diagnosis. In a comprehensive search we identified 68 studies. Subgroup analyses were carried out by technique, immunoglobulin class, and source of test (commercial and in-house). The results demonstrated: 1) WB tests showed high overall performance, sensitivity 91.3% (95% CI, 88.9–93.3), specificity 89% (95% CI, 85.7–91.9), LR+ 8.2 (95% CI, 5.1–13.3), LR− 0.06 (95% CI, 0.02–0.16), DOR 158.8 (95% CI, 57.8–435.8); 2) ELISA-IgG assays showed low sensitivity 79.2% (95% CI, 77.3–81.0) and high specificity (92.4%, 95% CI, 91.6–93.3); 3) ELISA commercial tests varied widely in performance (test for heterogeneity p<0.0001); and 4) In-house ELISA with whole-cell antigen tests showed the highest overall performance: sensitivity 94% (95% CI, 90.2–96.7), specificity 96.4% (95% CI, 94.2–97.9), LR+ 19.9 (95% CI, 7.9–49.8), LR− 0.08 (95% CI, 0.04–0.15) DOR 292.8 (95% CI, 101.8–841.7).
WB test and in-house ELISA with whole-cell antigen tests are the most reliable tests for the diagnosis of H. pylori infection in children. Antigens obtained from local strains of the community could partially explain the good overall accuracy of the in-house ELISA. Because of its cost and technical demands, in-house ELISA might be more suitable for use in developing countries.
PMCID: PMC2582133  PMID: 19015732
8.  The cost-effectiveness of a school-based overweight program 
This study assesses the net benefit and the cost-effectiveness of the Coordinated Approach to Child Health (CATCH) intervention program, using parameter estimates from the El Paso trial. There were two standard economic measures used. First, from a societal perspective on costs, cost-effectiveness ratios (CER) were estimated, revealing the intervention costs per quality-adjusted life years (QALYs) saved. QALY weights were estimated using National Health Interview Survey (NHIS) data. Second, the net benefit (NB) of CATCH was estimated, which compared the present value of averted future costs with the cost of the CATCH intervention. Using National Health and Nutrition Examination Survey I (NHANES) and NHANES follow-up data, we predicted the number of adult obesity cases avoided for ages 40–64 with a lifetime obesity progression model.
The results show that CATCH is cost-effective and net beneficial. The CER was US$900 (US$903 using Hispanic parameters) and the NB was US$68,125 (US$43,239 using Hispanic parameters), all in 2004 dollars. This is much lower than the benchmark for CER of US$30,000 and higher than the NB of US$0. Both were robust to sensitivity analyses.
Childhood school-based programs such as CATCH are beneficial investments. Both NB and CER declined when Hispanic parameters were included, primarily due to the lower wages earned by Hispanics. However, both NB and CER for Hispanics were well within standard cost-effectiveness and net benefit thresholds.
PMCID: PMC2098777  PMID: 17908315
9.  Evaluation of a Fast Test to Identify the Presence of Proline Aminopeptidase in Women With Bacterial Vaginosis 
Objective: The purpose of this study was to evaluate the activity of proline aminopeptidase by a rapid paper strip test in women with bacterial vaginosis (BV).
Methods: Vaginal secretions of 1,387 voluntary patients attending the Obstetrics and Gynecology Infectious Diseases Clinic at Juárez Hospital of Mexico City were collected and examined. Patients were assigned into 2 groups: 483 with BV according to clinical and laboratory criteria and 604 without BV as the control group. For the purposes of this study, 300 patients with trichomonas and/or yeast were excluded from the BV group. The strips were prepared by using L-proline β-naphthylamide and L-proline p-nitroanilide as the substrates to detect proline aminopeptidase activity in concentrated vaginal secretions. In parallel, all samples were also analyzed with the standard methods in microplates containing either sustrate as a control of the rapid strip test. The test was interpreted after 3–5 min of incubation.
Results: The results in the strip and microplate assays were similar in 95% of the samples. Sensitivity was 91.7% and specificity was 94.2%; probability of BV if the test is positive was 92.6% and negative predictive value was 93.4%.
Conclusions: These findings indicate that this aminopeptidase rapid strip assay provides a 3–5 min identification of activity of the enzyme in women with BV. The procedure is a rapid, non-expensive, sensitive, and useful test at the gynecologic clinic.
PMCID: PMC2364536  PMID: 18476142

Results 1-9 (9)