RESUMO
RESUMEN Introducción: La salud, como meta a lograr, se ha conceptualizado en cuanto a los diferentes países, momentos y contextos socio-históricos, condiciones económicas y criterios de organizaciones y autores. Objetivo: Establecer un consenso ajustado a la actualidad, con punto de partida en los conceptos de salud más difundidos y aceptados. Métodos: Se realizó un análisis de diferentes artículos, revistas y libros publicados relacionados con el tema, además de una revisión de bibliografía impresa y una búsqueda en Internet a través de Google e Infomed. El proceso de revisión se extendió entre octubre de 2019 y enero de 2020. Se analizó cada concepto enunciado y se tuvieron en cuenta las experiencias de los autores en diferentes momentos de su vida personal y profesional, dentro y fuera del país. Conclusiones: En esta investigación se demostraron las carencias de cada concepto enunciado. Luego de su valoración, se propuso un concepto de salud propio para los estándares de Cuba (sin limitar su aplicación fuera de las fronteras del país) relacionado con la realidad actual y el Sistema Integral de Salud.
ABSTRACT Introduction: health, as a goal to be achieved, has been conceptualized in terms of different countries, socio-historical contexts and moments, economic conditions and criteria of organizations and authors. Objective: to establish a consensus in line with the current state of the art, based on the most widespread and accepted health concepts. Methods: an analysis of different published articles, journals and books related to the topic was carried out, in addition to a review of printed literature and an Internet search using Google and Infomed. The review process lasted from October 2019 to January 2020. Each concept was analyzed and authors' experiences in different moments of their personal and professional lives, inside and outside the country, were taken into account. Conclusions: shortcomings of each enunciated concept were demonstrated in this research. After its evaluation, a health concept was proposed for Cuban standards related to the current reality and the Integrated Health System (without limiting its application outside the country's borders).
Assuntos
Saúde , Nível de SaúdeRESUMO
RESUMEN Introducción: la promoción de salud constituye una herramienta fundamental en la práctica médica ya que va más allá de la mera información al paciente sobre su dolencia y tratamiento. Objetivos: analizar la bibliografía seleccionada sobre la promoción y prevención de salud. Métodos: se tomaron como base criterios personales y un grupo de conceptos y definiciones sobre promoción y prevención de salud con la finalidad de provocar el debate y la polémica entre los profesionales. Se realizó la revisión de disímiles bibliografías cubanas y extranjeras, relacionadas con este tema y con temas afines. Se analizaron diferentes criterios sobre lo que realmente significa promover salud en sus tres dimensiones: biológica, psicológica y social. Esto constituye una herramienta para el personal sanitario sin distinción de perfiles ni niveles de atención en dependencia de su trabajo. Conclusiones: se concluyó que la promoción y el tratamiento forman parte indisoluble de la práctica médica actual.
ABSTRACT Introduction: health promotion constitutes a fundamental tool in medical practice since it goes beyond mere information to patients about their disease and treatment. Objective: to analyze the selected bibliography on health promotion and prevention. Methods: various personal criteria and a group of concepts and definitions on health promotion and prevention were taken as a basis in order to provoke debate and controversy among professionals. A review of dissimilar Cuban and foreign bibliographies related to this topic and related topics was carried out; different criteria were analyzed on what it really means to promote health in its three biological, psychological and social dimensions. This constitutes a tool for health personnel without distinction of profiles or levels of care depending on their work. Conclusions: we concluded that promotion and treatment are an inseparable part of current medical practice.
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Promoção da SaúdeRESUMO
Cation channel of sperm (CatSper), the main sperm-specific Ca2+ channel, plays a key role in mammalian fertilization, and it is essential for male fertility, becoming an attractive target for contraception. Based on this, in the present work, we investigated the effects of CatSper inactivation on in vitro and in vivo sperm fertilizing ability and the mechanisms underlying such effects. Exposure of cauda epididymal mouse sperm to different concentrations (1-20 µM) of the potent CatSper inhibitor HC-056456 (HC) during in vitro capacitation showed no effects on sperm viability but significantly affected Ca2+ entry into the cells, progressive motility, protein tyrosine phosphorylation, induced acrosome reaction, and hyperactivation, as well as the sperm's ability to in vitro fertilize cumulus oocyte complexes and zona-free eggs. Whereas the presence of HC during gamete coincubation did not affect in vitro fertilization, exposure of either non-capacitating or already capacitated sperm to HC prior to gamete coincubation severely reduced fertilization, indicating that sperm function is affected by HC when the cells are incubated with the drug before sperm-egg interaction. Of note, insemination of HC-treated sperm into the uterus significantly or completely reduced the percentage of oviductal fertilized eggs showing, for the first time, the effects of a CatSper inhibitor on in vivo fertilization. These observations, together with the finding that HC affects sperm fertilizing ability independently of the sperm capacitation status, provide further insights on how CatSper regulates sperm function and represent a solid proof of concept for developing a male/female non-hormonal contraceptive based on the pharmacological blockage of CatSper activity.
RESUMO
Epididymal Cysteine Rich Secretory Proteins 1 and 4 (CRISP1 and CRISP4) associate with sperm during maturation and play different roles in fertilization. However, males lacking each of these molecules individually are fertile, suggesting compensatory mechanisms between these homologous proteins. Based on this, in the present work, we generated double CRISP1/CRISP4 knockout (DKO) mice and examined their reproductive phenotype. Our data showed that the simultaneous lack of the two epididymal proteins results in clear fertility defects. Interestingly, whereas most of the animals exhibited specific sperm fertilizing ability defects supportive of the role of CRISP proteins in fertilization, one third of the males showed an unexpected epididymo-orchitis phenotype with altered levels of inflammatory molecules and non-viable sperm in the epididymis. Further analysis showed that DKO mice exhibited an immature epididymal epithelium and abnormal luminal pH, supporting these defects as likely responsible for the different phenotypes observed. These observations reveal that CRISP proteins are relevant for epididymal epithelium differentiation and male fertility, contributing to a better understanding of the fine-tuning mechanisms underlying sperm maturation and immunotolerance in the epididymis with clear implications for human epididymal physiology and pathology.
Assuntos
Diferenciação Celular , Epididimo/metabolismo , Infertilidade Masculina/genética , Infertilidade Masculina/metabolismo , Glicoproteínas de Membrana/deficiência , Proteínas de Plasma Seminal/genética , Animais , Epididimo/patologia , Epitélio/metabolismo , Epitélio/patologia , Infertilidade Masculina/patologia , Masculino , Camundongos , Camundongos KnockoutRESUMO
Epididymal sperm protein CRISP1 has the ability to both regulate murine CatSper, a key sperm calcium channel, and interact with egg-binding sites during fertilization. In spite of its relevance for sperm function, Crisp1-/-mice are fertile. Considering that phenotypes can be influenced by the genetic background, in the present work mice from the original mixed Crisp1-/- colony (129/SvEv*C57BL/6) were backcrossed onto the C57BL/6 strain for subsequent analysis of their reproductive phenotype. Whereas fertility and fertilization rates of C57BL/6 Crisp1-/- males did not differ from those reported for mice from the mixed background, several sperm functional parameters were clearly affected by the genetic background. Crisp1-/- sperm from the homogeneous background exhibited defects in both the progesterone-induced acrosome reaction and motility not observed in the mixed background, and normal rather than reduced protein tyrosine phosphorylation. Additional studies revealed a significant decrease in sperm hyperactivation as well as in cAMP and protein kinase A (PKA) substrate phosphorylation levels in sperm from both colonies. The finding that exposure of mutant sperm to a cAMP analog and phosphodiesterase inhibitor overcame the sperm functional defects observed in each colony indicated that a common cAMP-PKA signaling defect led to different phenotypes depending on the genetic background. Altogether, our observations indicate that the phenotype of CRISP1 null males is modulated by the genetic context and reveal new roles for the protein in both the functional events and signaling pathways associated to capacitation.
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Fertilidade/genética , Fertilização/genética , Glicoproteínas de Membrana/genética , Reprodução/genética , Espermatozoides/metabolismo , Reação Acrossômica/efeitos dos fármacos , Reação Acrossômica/genética , Animais , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Feminino , Patrimônio Genético , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fosforilação , Progesterona/farmacologia , Motilidade dos Espermatozoides/genética , Espermatozoides/efeitos dos fármacosRESUMO
A wide range of insecticide resistance profiles has been reported across Bolivian domestic and sylvatic populations of Triatoma infestans (Klug, 1834) (Hemiptera, Reduviidae), including some with levels proven to be a threat for vector control. In this work, the insecticide profile of domestic T. infestans was studied with standardized toxicological bioassays, in an area that has not undergone consistent vector control. F1 first-instar nymphs hatched in laboratory from bugs captured in three communities from the Santa Cruz Department were evaluated with different insecticides. Moreover, the enzymatic activity of esterases and cytochrome P450 monooxygenases was measured in individual insects to evaluate the possible mechanism of metabolic resistance to pyrethroids. In addition, the DNA sequence of sodium channel gene (kdr) was screened for two point mutations associated with pyrethroid resistance previously reported in T. infestans.All populations showed reduced susceptibility to deltamethrin and α-cypermethrin, albeit the RR50 values varied significantly among them. Increased P450 monooxygenases and permethrate esterases suggest the contribution, as detoxifying mechanisms, to the observed resistance to deltamethrin in all studied populations. No individuals presented either mutation associated to resistance in the kdr gene. The level of susceptibility to α-cypermethrin, the insecticide used by the local vector control program, falls within an acceptable range to continue its use in these populations. However, the observed RR50 values evidence the possibility of selection for resistance to pyrethroids, especially to deltamethrin. Consequently, the use of pyrethroid insecticides should be closely monitored in these communities, which should be kept under entomological surveillance and sustained interventions.
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Proteínas de Insetos/genética , Resistência a Inseticidas , Inseticidas/farmacologia , Nitrilas/farmacologia , Piretrinas/farmacologia , Triatoma/efeitos dos fármacos , Animais , Bolívia , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Esterases/genética , Esterases/metabolismo , Humanos , Proteínas de Insetos/metabolismo , Ninfa/efeitos dos fármacos , Ninfa/enzimologia , Ninfa/genética , Ninfa/crescimento & desenvolvimento , População Rural , Triatoma/enzimologia , Triatoma/genética , Triatoma/crescimento & desenvolvimento , Canais de Sódio Disparados por Voltagem/genética , Canais de Sódio Disparados por Voltagem/metabolismoRESUMO
A wide range of insecticide resistance profiles has been reported across Bolivian domestic and sylvatic populations of Triatoma infestans (Klug, 1834) (Hemiptera, Reduviidae), including some with levels proven to be a threat for vector control. In this work, the insecticide profile of domestic T. infestans was studied with standardized toxicological bioassays, in an area that has not undergone consistent vector control. F1 first-instar nymphs hatched in laboratory from bugs captured in three communities from the Santa Cruz Department were evaluated with different insecticides. Moreover, the enzymatic activity of esterases and cytochrome P450 monooxygenases was measured in individual insects to evaluate the possible mechanism of metabolic resistance to pyrethroids. In addition, the DNA sequence of sodium channel gene (kdr) was screened for two point mutations associated with pyrethroid resistance previously reported in T. infestans. All populations showed reduced susceptibility to deltamethrin and α-cypermethrin, albeit the RR50 values varied significantly among them. Increased P450 monooxygenases and permethrate esterases suggest the contribution, as detoxifying mechanisms, to the observed resistance to deltamethrin in all studied populations. No individuals presented either mutation associated to resistance in the kdr gene. The level of susceptibility to α-cypermethrin, the insecticide used by the local vector control program, falls within an acceptable range to continue its use in these populations. However, the observed RR50 values evidence the possibility of selection for resistance to pyrethroids, especially to deltamethrin. Consequently, the use of pyrethroid insecticides should be closely monitored in these communities, which should be kept under entomological surveillance and sustained interventions.
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Piretrinas , Triatoma , Resistência a Inseticidas , Doença de Chagas , InseticidasRESUMO
The prevention of Chagas disease is based primarily on the chemical control of Triatoma infestans (Klug) using pyrethroid insecticides. However, high resistance levels, correlated with control failures, have been detected in Argentina and Bolivia. A previous study at our laboratory found that imidacloprid could serve as an alternative to pyrethroid insecticides. We studied the delayed toxicity of imidacloprid and the influence of the blood feeding condition of the insect on the toxicity of this insecticide; we also studied the effectiveness of various commercial imidacloprid formulations against a pyrethroid-resistant T. infestans population from the Gran Chaco ecoregion. Variations in the toxic effects of imidacloprid were not observed up to 72 h after exposure and were not found to depend on the blood feeding condition of susceptible and resistant individuals. Of the three different studied formulations of imidacloprid on glass and filter paper, only the spot-on formulation was effective. This formulation was applied to pigeons at doses of 1, 5, 20 and 40 mg/bird. The nymphs that fed on pigeons treated with 20 mg or 40 mg of the formulation showed a higher mortality rate than the control group one day and seven days post-treatment (p < 0.01). A spot-on formulation of imidacloprid was effective against pyrethroid-resistant T. infestans populations at the laboratory level.
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Animais , Insetos Vetores , Imidazóis/farmacologia , Inseticidas/farmacologia , Nitrocompostos/farmacologia , Piretrinas/farmacologia , Triatoma/efeitos dos fármacos , Argentina , Bolívia , Doença de Chagas/prevenção & controle , Doença de Chagas/transmissão , Columbidae/parasitologia , Comportamento Alimentar , Resistência a Inseticidas , Imidazóis/química , Insetos Vetores/metabolismo , Inseticidas/química , Nitrocompostos/química , Ninfa/efeitos dos fármacos , Triatoma/classificação , Triatoma/metabolismoRESUMO
The prevention of Chagas disease is based primarily on the chemical control of Triatoma infestans (Klug) using pyrethroid insecticides. However, high resistance levels, correlated with control failures, have been detected in Argentina and Bolivia. A previous study at our laboratory found that imidacloprid could serve as an alternative to pyrethroid insecticides. We studied the delayed toxicity of imidacloprid and the influence of the blood feeding condition of the insect on the toxicity of this insecticide; we also studied the effectiveness of various commercial imidacloprid formulations against a pyrethroid-resistant T. infestans population from the Gran Chaco ecoregion. Variations in the toxic effects of imidacloprid were not observed up to 72 h after exposure and were not found to depend on the blood feeding condition of susceptible and resistant individuals. Of the three different studied formulations of imidacloprid on glass and filter paper, only the spot-on formulation was effective. This formulation was applied to pigeons at doses of 1, 5, 20 and 40 mg/bird. The nymphs that fed on pigeons treated with 20 mg or 40 mg of the formulation showed a higher mortality rate than the control group one day and seven days post-treatment (p < 0.01). A spot-on formulation of imidacloprid was effective against pyrethroid-resistant T. infestans populations at the laboratory level.
Assuntos
Imidazóis/farmacologia , Insetos Vetores , Inseticidas/farmacologia , Nitrocompostos/farmacologia , Piretrinas/farmacologia , Triatoma/efeitos dos fármacos , Animais , Argentina , Bolívia , Doença de Chagas/prevenção & controle , Doença de Chagas/transmissão , Columbidae/parasitologia , Comportamento Alimentar , Imidazóis/química , Insetos Vetores/metabolismo , Resistência a Inseticidas , Inseticidas/química , Neonicotinoides , Nitrocompostos/química , Ninfa/efeitos dos fármacos , Triatoma/classificação , Triatoma/metabolismoRESUMO
The aim of the present work was to study the deltamethrin susceptibility of eggs from Triatoma infestans populations and the contribution of pyrethroid esterases to deltamethrin degradation. Insects were collected from sylvatic areas, including Veinte de Octubre and Kirus-Mayu (Bolivia) and from domiciliary areas, including El Palmar (Bolivia) and La Pista (Argentina). Deltamethrin susceptibility was determined by dose-response bioassays. Serial dilutions of deltamethrin (0.0005-1 mg/mL) were topically applied to 12-day-old eggs. Samples from El Palmar had the highest lethal dose ratio (LDR) value (44.90) compared to the susceptible reference strain (NFS), whereas the Veinte de Octubre samples had the lowest value (0.50). Pyrethroid esterases were evaluated using 7-coumaryl permethrate (7-CP) on individually homogenised eggs from each population and from NFS. The El Palmar and La Pista samples contained 40.11 and 36.64 pmol/min/mg protein, respectively, and these values were statistically similar to NFS (34.92 pmol/min/mg protein) and different from Kirus-Mayu and Veinte de Octubre (27.49 and 22.69 pmol/min/mg protein, respectively). The toxicological data indicate that the domestic populations were resistant to deltamethrin, but no statistical contribution of 7-CP esterases was observed. The sylvatic populations had similar LDR values to NFS, but lower 7-CP esterase activities. Moreover, this is the first study of the pyrethroid esterases on T. infestans eggs employing a specific substrate (7-CP).