The p,p'-DDE disturbs the M1 function without affecting the M2 phenotype nor unstimulated bone marrow-derived macrophages from BALB/c mice.

DDT, a persistent organic pollutant, remains affecting human health worldwide. DDT and its most persistent metabolite (p,p'-DDE) negatively affect the immune response regulation and mechanisms involved in protecting against pathogens Such metabolite decreases the capability to limit intracellular growth of Mycobacterium microti and yeast. However, the effect on unstimulated (M0) and anti-inflammatory macrophages (M2) has been evaluated scanty. Herein, we evaluated the impact of p,p'-DDE at environmentally relevant concentrations (0.125, 1.25, 2.5, and 5 µg/mL) on bone marrow-derived macrophages stimulated with IFNγ+LPS to M1 or with IL-4 +IL-13 to M2. Thus we study whether the p,p'-DDE induces M0 to a specific phenotype or modulates activation of the macrophage phenotypes and explains, at least partly, the reported effects of p,p'-DDE on the M1 function. The p,p'-DDE did not affect the cell viability of M0 or the macrophage phenotypes. In M1, the p,p'-DDE decreased NO•- production and IL-1ß secretion, but increasing cellular ROS and mitochondrial O2•-, but did not alter iNOS, TNF-α, MHCII, and CD86 protein expression nor affect M2 markers arginase activity, TGF-ß1, and CD206; p,p'-DDE, did not affect marker expression in M0 or M2, supporting that its effects on M1 parameters are not dependent on M0 nor M2 modulation. The decreasing of NO•- production by the p,p'-DDE without altering iNOS levels, Arginase activity, or TNF-α, but increasing cellular ROS and mitochondrial O2 suggests that p,p'-DDE interferes with the iNOS function but not with its transcription. The p,p'-DDE decreasing of IL-1ß secretion, without any effect on TNF-α, suggest that an alteration of specific targets involved in IL-1ß secretion may be affected and related to ROS induction. The p,p'-DDE effect on iNOS function and the IL-1ß secretion process, as the NLRP3 activation, deserves further study.

Investigación en salud ambiental: La contribución peruana al Regional GEOHealth Hub Centered in Perú / Research in environmental health: The Peruvian contribution to the Regional GEOHealth Hub Centered in Peru

La presente publicación relata la contribución peruana en investigación en salud ambiental. En cinco capítulos se exploran diversos temas desarrollados en el programa GEOHealth Hub centered in Peru. Se aborda el tema de actualidad: Cambio climático. Además, se presentan investigaciones sobre la contaminación del aire, capítulo que se divide en calidad del aire interior y exterior donde abordamos las partículas emitidas por procesos antropogénicos y su impacto en la salud, no dejando de lado los compuestos orgánicos volátiles y la interacción del virus Sars-CoV-2 con el medio ambiente. El agua es un alimento indispensable para el ser humano, en éste capítulo se revisan los temas del saneamiento , seguridad alimentaria y el impacto en la salud humana por la contaminación del agua con arsénico en el Perú. El capítulo de metodología de la investigación propone estrategias para el manejo y análisis de datos para una investigación a través de fuente primaria o secundaria. El último capítulo es una miscelánea de temas de interés socioambiental con impacto a la salud, así como de educación ambiental y fiscalización ambiental

Agonists and protein kinase C-activation induce phosphorylation and internalization of FFA1 receptors.

FFA1 (previously known as GPR40) is a free fatty acid receptor involved in the regulation of inflammatory processes and insulin secretion. The cellular actions resulting from FFA1 activation have received considerable attention. However, little is known on the regulation of the receptor function. In the present work, using cells transfected with this receptor, docosahexaenoic acid and α-linolenic acid increased intracellular calcium concentration and ERK 1/2 phosphorylation. It was also observed that FFA1 is a phosphoprotein whose phosphorylation state was increased (2- to 3-fold) by agonists (i.e., free fatty acids) and also by phorbol myristate acetate. Agonist- and phorbol ester-mediated FFA1 phosphorylation was markedly reduced by inhibitors of protein kinase C. Receptor stimulation by free fatty acids and protein kinase C activation also induced receptor internalization as evidenced by confocal microscopy. In summary, our data show that FFA1 is a phosphoprotein whose phosphorylation state is modulated by agonists and protein kinase C activation; such covalent modification is associated with receptor internalization.

α1B-adrenergic receptors differentially associate with Rab proteins during homologous and heterologous desensitization.

Internalization of G protein-coupled receptors can be triggered by agonists or by other stimuli. The process begins within seconds of cell activation and contributes to receptor desensitization. The Rab GTPase family controls endocytosis, vesicular trafficking, and endosomal fusion. Among their remarkable properties is the differential distribution of its members on the surface of various organelles. In the endocytic pathway, Rab 5 controls traffic from the plasma membrane to early endosomes, whereas Rab 4 and Rab 11 regulate rapid and slow recycling from early endosomes to the plasma membrane, respectively. Moreover, Rab 7 and Rab 9 regulate the traffic from late endosomes to lysosomes and recycling to the trans-Golgi. We explore the possibility that α1B-adrenergic receptor internalization induced by agonists (homologous) and by unrelated stimuli (heterologous) could involve different Rab proteins. This possibility was explored by Fluorescence Resonance Energy Transfer (FRET) using cells coexpressing α1B-adrenergic receptors tagged with the red fluorescent protein, DsRed, and different Rab proteins tagged with the green fluorescent protein. It was observed that when α1B-adrenergic receptors were stimulated with noradrenaline, the receptors interacted with proteins present in early endosomes, such as the early endosomes antigen 1, Rab 5, Rab 4, and Rab 11 but not with late endosome markers, such as Rab 9 and Rab 7. In contrast, sphingosine 1-phosphate stimulation induced rapid and transient α1B-adrenergic receptor interaction of relatively small magnitude with Rab 5 and a more pronounced and sustained one with Rab 9; interaction was also observed with Rab 7. Moreover, the GTPase activity of the Rab proteins appears to be required because no FRET was observed when dominant-negative Rab mutants were employed. These data indicate that α1B-adrenergic receptors are directed to different endocytic vesicles depending on the desensitization type (homologous vs. heterologous).

Free fatty acids and protein kinase C activation induce GPR120 (free fatty acid receptor 4) phosphorylation.

GPR120, free fatty acid receptor 4, is a recently deorphanized G protein-coupled receptor that seems to play cardinal roles in the regulation of metabolism and in the pathophysiology of inflammatory and metabolic disorders. In the present work a GPR120-Venus fusion protein was expressed in HEK293 Flp-In T-REx cells and its function (increase in intracellular calcium) and phosphorylation were studied. It was observed that the fusion protein migrated in sodium dodecyl sulfate-polyacrylamide gels as a band with a mass of ≈70-75kDa, although other bands of higher apparent weight (>130kDa) were also detected. Cell stimulation with docosahexaenoic acid or α-linolenic acid induced concentration-dependent increases in intracellular calcium and GPR120 phosphorylation. Activation of protein kinase C with phorbol esters also induced a marked receptor phosphorylation but did not alter the ability of 1µM docosahexaenoic acid to increase the intracellular calcium concentration. Phorbol ester-induced GPR120 phosphorylation, but not that induced with docosahexaenoic acid, was blocked by protein kinase C inhibitors (bis-indolyl-maleimide I and Gö 6976) suggesting that conventional kinase isoforms mediate this action. The absence of effect of protein kinase C inhibitors on agonist-induced GPR120 phosphorylation indicates that this kinase does not play a major role in agonist-induced receptor phosphorylation. Docosahexaenoic acid action was associated with marked GPR120 internalization whereas that induced with phorbol esters was smaller at early times.

The decline in child mortality: a reappraisal

The present paper examines, describes and documents country-specific trends in under-five mortality rates (i.e., mortality among children under five years of age) in the 1990s. Our analysis updates previous studies by UNICEF, the World Bank and the United Nations. It identifies countries and WHO regions where sustained improvement has occurred and those where setbacks are evident. A consistent series of estimates of under-five mortality rate is provided and an indication is given of historical trends during the period 1950-2000 for both developed and developing countries. It is estimated that 10.5 million children aged 0-4 years died in 1999, about 2.2 million or 17,5 cent fewer than a decade earlier. On average about 15 cent of newborn children in Africa are expected to die before reaching their fifth birthday. The corresponding figures for many other parts of the developing world are in the range 3-8 cent and that for Europe is under 2 cent. During the 1990s the decline in child mortality decelerated in all the WHO regions except the Western Pacific but there is no widespread evidence of rising child mortality rates. At the coutry level there are exceptions in southern Africa where the prevalence of HIV is extremely high and in Asia where a few coutries are beset by economic difficulties. The slowdown in the rate of decline is of particular concern in Africa and South-East Asia because it is occurring at relatively high levels of mortality, and in coutries experiencing severe economic dislocation. As the HIV/AIDS epidemic continues in Africa, particularly southern Africa, and in parts of Asia, further reductions in child mortality become increasingly unlikely until substantial progress in controlling the spread of HIV is achieved

Estudio urodinámico en la incontinencia de orina femenina / Female urinary incontinence: urodynamic study

Se estudian 383 mujeres que consultaron por incontinencia urinaria. Se encuentran 290 casos con vejiga y uretra estable, 89 casos con vejiga inestable y uretra estable y 4 casos con vejiga estable y uretra inestable. Se comparan edad, capacidad cistométrica máxima, flujo máximo y presión uretral máxima de cierre en las vejigas inestables y las estables

Efecto del prazocin sobre ciertos parámetros urodinámicos en el adenoma de próstata / Prazocin effect on some urodynamic parameters in prostatic adenoma

Se estudian experimentalmente 40 enfermos con molestias disúricas por adenoma prostático grado I-II. Se dividen en 2 grupos por la administración de un bloqueador de receptores alfa 1 adrenérgicos (Prazocin 1 mg oral) o bien de un placebo. Se demuestra que la droga disminuye la presión uretral máxima de cierre y el residuo post-miccional, mejorando el flujo máximo

Combinador óptico de imágenes para la videocistometría sincrónica: descripción técnica / Optical combiner of images for sincronic videocystometry: technical description

Se presenta un equipo diseñado por los autores que permite disponer de la visión simultánea de las curvas urodinámicas y de la imagen radiografica del tracto urinario inferior. Tiene la ventaja de un costo reducido en comparación a los equipos comerciales