Compendio Nacional de Insumos para la Salud: equidad y acceso universal / National Compendium of Health Commodities: equity and universal access

Resumen: México fue pionero en establecer catálogos para identificar y hacer asequibles insumos médicos para la atención de su población, incluyendo medicamentos, instrumental, equipos y material de curación. Hace medio siglo, en 1971, surgió en el Instituto Mexicano del Seguro Social la iniciativa del llamado Cuadro Básico, que se constituyó como una herramienta fundamental para el funcionamiento de las instituciones públicas de salud, con la cual se establecieron listados de insumos con probada eficacia y seguridad, con claves administrativas asignadas que permitieron su adquisición ordenada. En 2020 se llevó a cabo la transición del Cuadro Básico y Catálogo al Compendio Nacional de Insumos para la Salud, el cual recuperó el espíritu original de sus creadores como un documento vivo y en constante evolución, respaldado por una metodología rigurosa para la revisión de los insumos que se incluyen, basada en la evaluación de su efectividad, seguridad y calidad, y en criterios farmacoeconómicos y consensos interinstitucionales.

Abstract: Mexico pioneered the creation of catalogs for identification and access of the medical commodities necessary for public healthcare, including medicines, medical equipment and wound dressing supplies. Fifty years ago, in 1971, the Instituto Mexicano del Seguro Social started the initiative of the Basic Scheme (Cuadro básico), that became a fundamental tool for provision of healthcare in the public institutions through the establishment of listings of medical supplies with proved safety and efficacy, assigning administrative codes that allowed an orderly acquisition. On 2020, the Basic Scheme and Catalog underwent a transition towards the National Compendium of Health Commodities (Compendio Nacional de Insumos para la Salud), recovering the original spirit of their creators as a live document in constant evolution, supported by a rigorous methodology for the assessment of the medical commodities included, based on evaluations of effectiveness, safety and quality, pharmacoeconomic criteria and interinstitutional consensus.

Compendio Nacional de Insumos para la Salud: equidad y acceso universal.

México fue pionero en establecer catálogos para identificar y hacer asequibles insumos médicos para la atención de su población, incluyendo medicamentos, instrumental, equipos y material de curación. Hace medio siglo, en 1971, surgió en el Instituto Mexicano del Seguro Social la iniciativa del llamado Cuadro Básico, que se constituyó como una herramienta fun-damental para el funcionamiento de las instituciones públicas de salud, con la cual se establecieron listados de insumos con probada eficacia y seguridad, con claves administrativas asignadas que permitieron su adquisición ordenada. En 2020 se llevó a cabo la transición del Cuadro Básico y Catálogo al Compendio Nacional de Insumos para la Salud, el cual recuperó el espíritu original de sus creadores como un do-cumento vivo y en constante evolución, respaldado por una metodología rigurosa para la revisión de los insumos que se incluyen, basada en la evaluación de su efectividad, seguridad y calidad, y en criterios farmacoeconómicos y consensos interinstitucionales.

A transcriptome-based model of central memory CD4 T cell death in HIV infection.

BACKGROUND: Human central memory CD4 T cells are characterized by their capacity of proliferation and differentiation into effector memory CD4 T cells. Homeostasis of central memory CD4 T cells is considered a key factor sustaining the asymptomatic stage of Human Immunodeficiency Virus type 1 (HIV-1) infection, while progression to acquired immunodeficiency syndrome is imputed to central memory CD4 T cells homeostatic failure. We investigated if central memory CD4 T cells from patients with HIV-1 infection have a gene expression profile impeding proliferation and survival, despite their activated state. METHODS: Using gene expression microarrays, we analyzed mRNA expression patterns in naive, central memory, and effector memory CD4 T cells from healthy controls, and naive and central memory CD4 T cells from patients with HIV-1 infection. Differentially expressed genes, defined by Log2 Fold Change (FC) ≥ |0.5| and Log (odds) > 0, were used in pathway enrichment analyses. RESULTS: Central memory CD4 T cells from patients and controls showed comparable expression of differentiation-related genes, ruling out an effector-like differentiation of central memory CD4 T cells in HIV infection. However, 210 genes were differentially expressed in central memory CD4 T cells from patients compared with those from controls. Expression of 75 of these genes was validated by semi quantitative RT-PCR, and independently reproduced enrichment results from this gene expression signature. The results of functional enrichment analysis indicated movement to cell cycle phases G1 and S (increased CCNE1, MKI67, IL12RB2, ADAM9, decreased FGF9, etc.), but also arrest in G2/M (increased CHK1, RBBP8, KIF11, etc.). Unexpectedly, the results also suggested decreased apoptosis (increased CSTA, NFKBIA, decreased RNASEL, etc.). Results also suggested increased IL-1ß, IFN-γ, TNF, and RANTES (CCR5) activity upstream of the central memory CD4 T cells signature, consistent with the demonstrated milieu in HIV infection. CONCLUSIONS: Our findings support a model where progressive loss of central memory CD4 T cells in chronic HIV-1 infection is driven by increased cell cycle entry followed by mitotic arrest, leading to a non-apoptotic death pathway without actual proliferation, possibly contributing to increased turnover.

Oxidant status and lipid composition of erythrocyte membranes in patients with type 2 diabetes, chronic liver damage, and a combination of both pathologies.

There is an important set of cirrhotic and diabetic patients that present both diseases. However, information about metabolic and cellular blood markers that are altered, in conjunction or distinctively, in the 3 pathological conditions is scarce. The aim of this project was to evaluate several indicators of prooxidant reactions and the membrane composition of blood samples (serum and red blood cells (RBCs)) from patients clinically classified as diabetic (n = 60), cirrhotic (n = 70), and diabetic with liver cirrhosis (n = 25) as compared to samples from a similar population of healthy individuals (n = 60). The results showed that levels of TBARS, nitrites, cysteine, and conjugated dienes in the RBC of cirrhotic patients were significantly increased. However, the coincidence of diabetes and cirrhosis partially reduced the alterations promoted by the cirrhotic condition. The amount of total phospholipids and cholesterol was greatly enhanced in the patients with both pathologies (between 60 and 200% according to the type of phospholipid) but not in the patients with only one disease. Overall, the data indicate that the cooccurrence of diabetes and cirrhosis elicits a physiopathological equilibrium that is different from the alterations typical of each individual malady.

Seasonal and pandemic influenza H1N1 viruses induce differential expression of SOCS-1 and RIG-I genes and cytokine/chemokine production in macrophages.

BACKGROUND: Infection with pandemic (pdm) A/H1N1 virus induces high levels of pro-inflammatory mediators in blood and lungs of experimental animals and humans. METHODS: To compare the involvement of seasonal A/PR/8/34 and pdm A/H1N1 virus strains in the regulation of inflammatory responses, we analyzed the changes in the whole-genome expression induced by these strains in macrophages and A549 epithelial cells. We also focused on the functional implications (cytokine production) of the differential induction of suppressors of cytokine signaling (SOCS)-1, SOCS-3, retinoid-inducible gene (RIG)-I and interferon receptor 1 (IFNAR1) genes by these viral strains in early stages of the infection. RESULTS: We identified 130 genes differentially expressed by pdm A/H1N1 and A/PR/8/34 infections in macrophages. mRNA levels of SOCS-1 and RIG-I were up-regulated in macrophages infected with the A/PR/8/34 but not with pdm A/H1N1 virus. mRNA levels of SOCS-3 and IFNAR1 induced by A/PR/8/34 and pdm A/H1N1 strains in macrophages, as well as in A549 cells were similar. We found higher levels of IL-6, TNF-α, IL-10, CCL3, CCL5, CCL4 and CXCL8 (p < 0.05) in supernatants from cultures of macrophages infected with the pdm A/H1N1 virus compared to those infected with the A/PR/8/34 strain, coincident with the lack of SOCS-1 and RIG-I expression. In contrast, levels of INF-α were higher in cultures of macrophages 48h after infection with the A/PR/8/34 strain than with the pdm A/H1N1 virus. CONCLUSIONS: These findings suggest that factors inherent to the pdm A/H1N1 viral strain may increase the production of inflammatory mediators by inhibiting SOCS-1 and modifying the expression of antiviral immunity-related genes, including RIG-I, in human macrophages.

Galectin-1 promotes human neutrophil migration.

An important step of innate immune response is the recruitment of polymorphonuclear leukocytes (PMN) to injured tissues through chemotactic molecules. Galectins, a family of endogenous lectins, participate in numerous functions such as lymphoid cell migration, homing, cell-cell and cell-matrix interactions. Particularly, galectin-3 (Gal-3) and -9 have been implicated in the modulation of acute and chronic inflammation by inducing the directional migration of monocytes/macrophages and eosinophils, whereas Gal-1 is considered to function as an anti-inflammatory molecule, capable of inhibiting the influx of PMN to the site of injury. In this study, we assessed the effect of Gal-1 on neutrophil recruitment, in the absence of additional inflammatory insults. Contrasting with its capacity to inhibit cell trafficking and modulate the release of mediators described in models of acute inflammation and autoimmunity, we evidenced that Gal-1 has the capacity to induce neutrophil migration both in vitro and in vivo. This effect is not mediated through a G-protein-coupled receptor but potentially through the sialoglycoprotein CD43, via carbohydrate binding and through the p38 mitogen-activated protein kinase pathway. These results suggest a novel biological function for CD43 on neutrophils and highlight that depending on the environment, Gal-1 can act either as chemoattractant or, as a molecule that negatively regulates migration under acute inflammatory conditions, underscoring the potential of Gal-1 as a target for innovative drug development.

[Systemic lupus erythematosus: genomics of the disease]. / Lupus eritematoso sistémico (LES): genómica de la enfermedad.

Systemic lupus erythematosus (SLE) is the prototype of autoimmune diseases with multiple autoantigens as targets,resulting in damage to many organs of the body. The disease is more common in females (> 90%) and around 15% of the cases present during childhood.Systemic lupus erythematosus is a complex disease in which both genetic (susceptibility/protection alleles) and environmental factors (infections, drugs, stress, etc.) contribute to its development.The current knowledge on genetic factors involved in SLE is based on the results of linkage analyses in multi-case families as well as from case-control or family-based genetic association studies. These types of genetic analyses have contributed to identifying susceptibility genes and constitute the first step towards understanding the molecular mechanisms underlying SLE.The aim of this review is to provide a current picture of the genes identified as susceptibility factors for SLE, and to highlight the ones described in the Mexican population.

Identification of loci controlling restriction of parasite growth in experimental Taenia crassiceps cysticercosis.

Human neurocysticercosis (NC) caused by Taenia solium is a parasitic disease of the central nervous system that is endemic in many developing countries. In this study, a genetic approach using the murine intraperitoneal cysticercosis caused by the related cestode Taenia crassiceps was employed to identify host factors that regulate the establishment and proliferation of the parasite. A/J mice are permissive to T. crassiceps infection while C57BL/6J mice (B6) are comparatively restrictive, with a 10-fold difference in numbers of peritoneal cysticerci recovered 30 days after infection. The genetic basis of this inter-strain difference was explored using 34 AcB/BcA recombinant congenic strains derived from A/J and B6 progenitors, that were phenotyped for T. crassiceps replication. In agreement with their genetic background, most AcB strains (A/J-derived) were found to be permissive to infection while most BcA strains (B6-derived) were restrictive with the exception of a few discordant strains, together suggesting a possible simple genetic control. Initial haplotype association mapping using >1200 informative SNPs pointed to linkages on chromosomes 2 (proximal) and 6 as controlling parasite replication in the AcB/BcA panel. Additional linkage analysis by genome scan in informative [AcB55xDBA/2]F1 and F2 mice (derived from the discordant AcB55 strain), confirmed the effect of chromosome 2 on parasite replication, and further delineated a major locus (LOD = 4.76, p<0.01; peak marker D2Mit295, 29.7 Mb) that we designate Tccr1 (T. crassiceps cysticercosis restrictive locus 1). Resistance alleles at Tccr1 are derived from AcB55 and are inherited in a dominant fashion. Scrutiny of the minimal genetic interval reveals overlap of Tccr1 with other host resistance loci mapped to this region, most notably the defective Hc/C5 allele which segregates both in the AcB/BcA set and in the AcB55xDBA/2 cross. These results strongly suggest that the complement component 5 (C5) plays a critical role in early protective inflammatory response to infection with T. crassiceps.

Resistance to acute babesiosis is associated with interleukin-12- and gamma interferon-mediated responses and requires macrophages and natural killer cells.

We examined the role of the cytokines gamma interferon (IFN-gamma) and interleukin-12 (IL-12) in the model of acute babesiosis with the WA1 Babesia. Mice genetically deficient in IFN-gamma-mediated responses (IFNGR2KO mice) and IL-12-mediated responses (Stat4KO mice) were infected with the WA1 Babesia, and observations were made on the course of infection and cytokine responses. Levels of IFN-gamma and IL-12 in serum increased 24 h after parasite inoculation. The augmented susceptibility observed in IFNGR2KO and Stat-4KO mice suggests that the early IL-12- and IFN-gamma-mediated responses are involved in protection against acute babesiosis. Resistance appears to correlate with an increase in nitric oxide (NO) production. In order to assess the contribution of different cell subsets to resistance against the parasite, we also studied mice lacking B cells, CD4+ T cells, NK cells, and macrophages. Mice genetically deficient in B lymphocytes or CD4+ T lymphocytes were able to mount protective responses comparable to those of immunosufficient mice. In contrast, in vivo depletion of macrophages or NK cells resulted in elevated susceptibility to the infection. Our observations suggest that a crucial part of the response that protects from the pathogenic Babesia WA1 is mediated by macrophages and NK cells, probably through early production of IL-12 and IFN-gamma, and induction of macrophage-derived effector molecules like NO.