[State and capital accumulation in Brazilian health from the perspective of the Marxist Dependency Theory]. / Estado e acumulação de capital na saúde brasileira sob a ótica da Teoria Marxista da Dependência.

The health sector is one of the major fields of economic, social, scientific, and technological development in Brazil, and has been the arena of dispute between capitalist interests that regard health as a commodity and advocates of universal access who regard health as an essential good. The Brazilian Federal Constitution of 1988 determined that health is a fundamental right and the State's responsibility, and since then the country has made progress with public policy, but has suffered setbacks and blockages due to its status as a peripheric country, historically subordinated to the interests of core countries, which see Brazil as a broad consumer market. These external interests associated with the internal bourgeoisie have been taking advantage of the Brazilian State since the 1960s, when the foundation of business groups expanded, dominating various health segments, especially since the neoliberal policies of the 1990s. These aspects are much explored in publications in Public Health, but this text seeks a new approach, using the Marxist Theory of Dependency as a reference to analyze, albeit in a preliminary way, the situation of political, economic, and technological dependence that has distanced health policy from the ideals of a public and universal system, defended in the Brazilian Health Reform.

O setor de saúde constitui um dos maiores campos de desenvolvimento econômico, social, científico e tecnológico do Brasil e tem sido arena de disputa entre os interesses capitalistas, que entendem a saúde como bem de mercado, e os defensores do acesso universal, que a entendem como bem essencial. No Brasil, a Constituição Federal de 1988 determinou que a saúde é direito de todos e dever do Estado, e, desde então, o país avança com a política pública, mas sofre recuos e bloqueios pela condição de país de economia periférica, historicamente subordinado aos interesses dos países centrais, que o veem como um amplo mercado consumidor. Esses interesses externos, associados à burguesia interna, têm obtido vantagens do Estado brasileiro desde a década de 1960, quando a formação de grupos empresariais se expandiu, dominando diversos segmentos da saúde, sobretudo a partir de políticas neoliberais dos anos de 1990. Esses aspectos são muito explorados nas publicações do campo da Saúde Coletiva, mas este texto busca uma nova abordagem, utilizando a Teoria Marxista da Dependência como referência para analisar, ainda que de forma preliminar, a situação de dependência política, econômica e tecnológica que tem distanciado a política de saúde dos ideais de um sistema público e universal, defendido na Reforma Sanitária brasileira.

El sector de la salud es uno de los mayores campos de desarrollo económico, social, científico y tecnológico de Brasil y ha sido un escenario de disputa entre los intereses capitalistas, que entienden la salud como un bien de mercado, y los defensores del acceso universal, que entienden la salud como un bien esencial. En Brasil, la Constitución Federal de 1988 estableció que la salud es un derecho de todos y un deber del Estado, y desde entonces el país ha avanzado con políticas públicas, no exentas de retrocesos y bloqueos debido a la condición de país de periferia económica, históricamente subordinado a los intereses de los países centrales, que ven a Brasil como un amplio mercado consumidor. Estos intereses externos, asociados a la burguesía interna, han obtenido ventajas del Estado brasileño desde la década de 1960, cuando se expandió la formación de grupos empresariales, dominando varios segmentos de la salud, sobre todo a partir de políticas neoliberales de la década de 1990. Estos aspectos son ampliamente explorados en publicaciones del campo de la Salud Colectiva, pero este texto busca un nuevo enfoque, utilizando la Teoría Marxista de la Dependencia como referencia para analizar, aunque de forma preliminar, la situación de dependencia política, económica y tecnológica que ha alejado la política de salud de los ideales de un sistema público y universal, defendido en la Reforma Sanitaria brasileña.

Environmentally friendly concrete block production: valorization of civil construction and chemical industry waste.

In the present work, a study was carried out on the dosage of wastes from the chemical industry (tannery sludge) and civil construction (concrete and plaster) in mixtures used in concrete blocks' production. The objective was the application of these blocks in paving. The characterization of the materials used was performed employing X-ray diffractometry (XRD), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS). The effect of the different residues on the blocks' properties was evaluated through compressive strength, flexion-traction, water absorption, abrasion resistance, and leaching tests. The results indicated that the concrete paving blocks produced with the addition of residues did not obtain gains in the values of mechanical resistance to compression and traction in bending compared to blocks made with standard raw material. However, the blocks produced with construction waste presented satisfactory results for application in street paving after 7 days of concrete curing, reaching values between 36.54 and 44.6 MPa for the mentioned properties. These values also increased to 21.4% within 28 days of curing. The blocks produced with plaster showed values between 37.03 and 39.85 MPa after 28 days of curing, allowing their use for street paving. On the other hand, the blocks containing residues from the chemical industry had lower strengths, reaching a maximum of 29.36 MPa after 28 days of curing. In addition, it was also noted that the blocks produced with recycled concrete showed an improvement in performance for a composition of 50% recycled material.

Influence of Molybdenum and Organic Sources of Copper and Sulfur on the Performance, Carcass Traits, Blood Mineral Concentration, and Ceruloplasmin Activity in Lambs.

This study aimed to evaluate the effects of molybdenum (Mo) and organic and inorganic sources of copper (Cu) and sulfur (S) on the performance, carcass traits, and blood concentration of these minerals in lambs. Forty male non-castrated crossbred Dorper x Santa Inês lambs (20 ± 1.2 kg of body weight and 90 ± 2 d of age) were randomly allocated into one of the ten following treatments: (T0) control, basal diet; (T1) Mo; (T2) inorganic Cu and inorganic S; (T3) inorganic Cu and organic S; (T4) organic Cu and inorganic S; (T5) organic Cu and organic S; (T6) Mo plus inorganic Cu and inorganic S; (T7) Mo plus inorganic Cu and organic S; (T8) Mo plus organic Cu and inorganic S; and (T9) Mo plus organic Cu and organic S. Regardless of the source, Mo, Cu, and S were added at levels of 10 mg, 10 mg, and 2000mg/kg DM, respectively. The mineral supplements (Mo, Cu, and S) were added into the total mixed ration (TMR) by mixing them apart with the mineral and vitamin premix and then put into the TMR. The animals were kept in individual pens and received a total mixed ration for 84 days. Body weight and blood sampling was performed every 28 days. All animals were slaughtered after 84 days, and carcass traits were evaluated. Although organic sources of Cu and S added to Mo supplementation had increased the ADG throughout the study, this effect did not reflect in the heavier final BW outcomes for this treatment. In addition, no effect of these treatments was observed on the carcass traits. The serum Cu concentration was higher for the T0 group compared to the other groups; otherwise, Mo reduced the serum Cu concentration compared to the other groups. Considering the interaction among the minerals and their sources at 84 d of study, organic sources of Cu and S treatment and Mo associated with inorganic sources of Cu plus organic S treatment had an increased serum Cu concentration compared to other groups. Regardless of time, organic sources of Cu and S increased serum S concentration. At 84 days after enrollment, serum Mo concentration was lower for the control group compared to the other groups. Further, Mo supplementation increased its blood concentration compared to the control group throughout the study. The control group had the highest ceruloplasmin activity compared to the other groups; otherwise, at 84 d of the study, either Mo or inorganic S supplementation reduced ceruloplasmin activity. Serum ceruloplasmin activity was higher when Cu supplementation, regardless of source, was associated with organic S. However, at d 84 of the study, inorganic Cu associated to organic S supplements increased serum ceruloplasmin activity. In this current study, it was not possible to identify a pattern in the variables studied, however, further studies are needed to confirm that organic sources of Cu and S interacted alone without a defined pattern.

Pigeon Pea Intercropped with Tropical Pasture as a Mitigation Strategy for Enteric Methane Emissions of Nellore Steers.

In this study, we evaluate the effects of intercropping pigeon pea (Cajanus cajan (L.) Millsp.) with tropical pastures for feeding Nellore cattle and compared animal performance and enteric CH4 emissions with other pasture-based systems during the dry and rainy seasons of 2021. Thirty-six Nellore steers (with a body weight of 221 ± 7 kg and an age of 15-16 months) were randomly distributed in three treatments with three replicates (in paddocks of 1.5 hectares each): (1) a degraded pasture of Urochloa spp. (DEG); (2) a recovered and fertilized pasture of Urochloa spp. (REC); and (3) pigeon pea intercropped with Urochloa spp. (MIX). Enteric CH4 emissions were estimated using the sulfur hexafluoride (SF6) tracer gas technique, and dry matter intake (DMI) was determined using internal (iNDF) and external (TiO2) markers. Forages were collected by hand plucking after observations of ingestive behavior, and feces was collected after voluntary defecation. The proportion of grass and legume intake was estimated by C stable isotopes, and the forage nutritional quality was determined, while animal performance was monitored monthly, and the stocking rate was adjusted by the "put and take" technique. The results indicated that intercropping pigeon pea with tropical grasses is an interesting strategy for sustainable livestock production based on pastures. The MIX treatment was able to meet the nutritional requirements of the animals, which presented higher performance. In addition, there was a reduction in CH4 emissions up to 70% when expressed per average daily weight gain in comparison to the DEG treatment.

Use of tannin extract as a strategy to reduce methane in Nellore and Holstein cattle and its effect on intake, digestibility, microbial efficiency and ruminal fermentation.

This study was carried out to evaluate the use of tannin extract from Acacia mearnsii as a strategy to reduce methane (CH4 ) in two distinct cattle genotypes and its effect on intake, digestibility, microbial efficiency and ruminal fermentation. Four Nellore (Bos indicus) and four Holstein (Bos taurus) dry cows fitted with rumen cannula were assigned to two 4 × 4 Latin square design, in a 2 × 4 factorial arrangement, where each genotype represented a square receiving four tannin levels (commercial extract of A. mearnsii) in the diet (0%, 0.5%, 1.0% and 1.5% of dry matter). Tannin levels used did not cause a reduction in feed intake or rumen passage rate for both genotypes (p > 0.05), although there was a linear reduction in the degradation rate and ruminal disappearance of diet (p < 0.05). The increase in tannin levels reduced the amount of entodiniomorph protozoa in the Nellore cattle (p < 0.05). There was no change in N retention or microbial efficiency (p > 0.05), despite the linear reduction of nutrient digestibility and the synthesis of microbial nitrogen (p < 0.05). The ruminal CH4 production was reduced (p < 0.05) without reducing the short-chain fatty acid production. The threshold of 0.72% of tannin in the diet was estimated as the starting point for the reduction of ruminal CH4 production with long-term efficacy. Therefore, the use of low levels of tannin extract from A. mearnsii is a potential option to manipulate rumen fermentation in Nellore and Holstein cattle and needs to be further investigated.

Estado e acumulação de capital na saúde brasileira sob a ótica da Teoria Marxista da Dependência / State and capital accumulation in Brazilian health from the perspective of the Marxist Dependency Theory / Estado y acumulación de capital en la salud brasileña desde la perspectiva de la Teoría Marxista de la Dependencia

Resumo: O setor de saúde constitui um dos maiores campos de desenvolvimento econômico, social, científico e tecnológico do Brasil e tem sido arena de disputa entre os interesses capitalistas, que entendem a saúde como bem de mercado, e os defensores do acesso universal, que a entendem como bem essencial. No Brasil, a Constituição Federal de 1988 determinou que a saúde é direito de todos e dever do Estado, e, desde então, o país avança com a política pública, mas sofre recuos e bloqueios pela condição de país de economia periférica, historicamente subordinado aos interesses dos países centrais, que o veem como um amplo mercado consumidor. Esses interesses externos, associados à burguesia interna, têm obtido vantagens do Estado brasileiro desde a década de 1960, quando a formação de grupos empresariais se expandiu, dominando diversos segmentos da saúde, sobretudo a partir de políticas neoliberais dos anos de 1990. Esses aspectos são muito explorados nas publicações do campo da Saúde Coletiva, mas este texto busca uma nova abordagem, utilizando a Teoria Marxista da Dependência como referência para analisar, ainda que de forma preliminar, a situação de dependência política, econômica e tecnológica que tem distanciado a política de saúde dos ideais de um sistema público e universal, defendido na Reforma Sanitária brasileira.

Abstract: The health sector is one of the major fields of economic, social, scientific, and technological development in Brazil, and has been the arena of dispute between capitalist interests that regard health as a commodity and advocates of universal access who regard health as an essential good. The Brazilian Federal Constitution of 1988 determined that health is a fundamental right and the State's responsibility, and since then the country has made progress with public policy, but has suffered setbacks and blockages due to its status as a peripheric country, historically subordinated to the interests of core countries, which see Brazil as a broad consumer market. These external interests associated with the internal bourgeoisie have been taking advantage of the Brazilian State since the 1960s, when the foundation of business groups expanded, dominating various health segments, especially since the neoliberal policies of the 1990s. These aspects are much explored in publications in Public Health, but this text seeks a new approach, using the Marxist Theory of Dependency as a reference to analyze, albeit in a preliminary way, the situation of political, economic, and technological dependence that has distanced health policy from the ideals of a public and universal system, defended in the Brazilian Health Reform.

Resumen: El sector de la salud es uno de los mayores campos de desarrollo económico, social, científico y tecnológico de Brasil y ha sido un escenario de disputa entre los intereses capitalistas, que entienden la salud como un bien de mercado, y los defensores del acceso universal, que entienden la salud como un bien esencial. En Brasil, la Constitución Federal de 1988 estableció que la salud es un derecho de todos y un deber del Estado, y desde entonces el país ha avanzado con políticas públicas, no exentas de retrocesos y bloqueos debido a la condición de país de periferia económica, históricamente subordinado a los intereses de los países centrales, que ven a Brasil como un amplio mercado consumidor. Estos intereses externos, asociados a la burguesía interna, han obtenido ventajas del Estado brasileño desde la década de 1960, cuando se expandió la formación de grupos empresariales, dominando varios segmentos de la salud, sobre todo a partir de políticas neoliberales de la década de 1990. Estos aspectos son ampliamente explorados en publicaciones del campo de la Salud Colectiva, pero este texto busca un nuevo enfoque, utilizando la Teoría Marxista de la Dependencia como referencia para analizar, aunque de forma preliminar, la situación de dependencia política, económica y tecnológica que ha alejado la política de salud de los ideales de un sistema público y universal, defendido en la Reforma Sanitaria brasileña.

Greenhouse gas balance and mitigation of pasture-based dairy production systems in the Brazilian Atlantic Forest Biome.

Brazilian cattle production is mostly carried out in pastures, and the need to mitigate the livestock's greenhouse gas (GHG) emissions and its environmental footprint has become an important requirement. The adoption of well-suited breeds and the intensification of pasture-based livestock production systems are alternatives to optimize the sector's land use. However, further research on tropical systems is necessary. The objective of this research was to evaluate the effect of Holstein (HO) and Jersey-Holstein (JE x HO) crossbred cows in different levels of pasture intensification (continuous grazing system with low stocking rate-CLS; irrigated rotational grazing system with high stocking rate-RHS), and the interaction between these two factors on GHG mitigation. Twenty-four HO and 24 JE x HO crossbred dairy cows were used to evaluate the effect of two grazing systems on milk production and composition, soil GHG emissions, methane (CH4) emission, and soil carbon accumulation (0-100 cm). These variables were used to calculate carbon balance (CB), GHG emission intensity, the number of trees required to mitigate GHG emission, and the land-saving effect. The number of trees necessary to mitigate GHG emission was calculated, considering the C balance within the farm gate. The mitigation of GHG emissions comes from the annual growth rate and accumulation of C in eucalyptus trees' trunks. The CB of all systems and genotypes presented a deficit in carbon (C); there was no difference for genotypes, but RHS was more deficient than CLS (-4.99 to CLS and -28.72 to RHS ton CO2e..ha-1.year-1). The deficit of C on GHG emission intensity was similar between genotypes and higher for RHS (-0.480 to RHS and -0.299 to CLS kg CO2e..kg FCPCmilk-1). Lower GHG removals (0.14 to CLS higher than 0.02 to RHS kg CO2e..kg FCPCmilk-1) had the greatest influence on the GHG emission intensity of milk production. The deficit number of trees to abatement emissions was higher to HO (-46.06 to HO and -38.37 trees/cow to JE x HO) and to RHS (-51.9 to RHS and -33.05 trees/cow to CLS). However, when the results are expressed per ton of FCPCmilk, there was a difference only between pasture management, requiring -6.34 tree. ton FCPCmilk-1 for the RHS and -3.99 tree. ton FCPCmilk-1 for the CLS system. The intensification of pastures resulted in higher milk production and land-saving effect of 2.7 ha. Due to the reservation of the pasture-based dairy systems in increasing soil C sequestration to offset the GHG emissions, especially enteric CH4, planting trees can be used as a mitigation strategy. Also, the land-save effect of intensification can contribute to the issue, since the area spared through the intensification in pasture management becomes available for reforestation with commercial trees.

[Recent changes and continuity of technological and economic dependency in the pharmaceutical industry in Brazil]. / Mudanças recentes e continuidade da dependência tecnológica e econômica na indústria farmacêutica no Brasil.

This article presents the results of a study on the pharmaceutical industry in Brazil in the recent period, as part of the multicenter project Health Economic-Industrial Complex, Innovation and Capitalist Dynamics: Structural Challenges for Construction of the Universal Health System in Brazil. The four components studied in the evolution of the Brazilian pharmaceutical industry were: State industrial policies; changes in the financial and shareholding composition of companies with domestic capital; trends in production; and trade balance behavior. The analyses considered the theoretical framework proposed by Luiz Filgueiras and Reinaldo Gonçalves concerning the implementation of a "liberal and peripheral model" in the Brazilian economy since the 1990s. Data were collected and analyzed on the situation with the Product Development Partnerships (PDP) for medicines from 2009 to 2020 from the Annual Industrial Survey (PIA) of the Brazilian Institute of Geography and Statistics (IBGE) from 1996 to 2018 and data on the evolution of the sector's trade balance from 1996 to 2019. The results show that the State's agenda for the sector favored the growth in production of generic drugs and over-the-counter drugs and started some technology transfer projects via PDPs for production of biological and synthetic drugs. Despite this evolution, Brazil is still dependent on the importation of chemical and pharmaceutical inputs and finished drugs. This keeps Brazil in a situation of technological and economic vulnerability in relation to global suppliers, besides a growing trade deficit in the sector.

Este artigo apresenta os resultados de pesquisa sobre a indústria farmacêutica no Brasil, no período recente, realizada no âmbito do projeto multicêntrico Complexo Econômico-Industrial da Saúde, Inovação e Dinâmica Capitalista: Desafios Estruturais para a Construção do Sistema Universal de Saúde no Brasil. Os quatro componentes estudados sobre a evolução da indústria farmacêutica no Brasil foram: as políticas industriais do Estado; as mudanças na composição financeira e patrimonial das empresas de capital nacional, a evolução da produção; e o comportamento da balança comercial. As análises levaram em consideração o marco teórico proposto por Luiz Filgueiras e Reinaldo Gonçalves a respeito da implantação de um "modelo liberal e periférico" na economia brasileira a partir dos anos 1990. Foram levantados e analisados dados sobre: a situação das Parcerias de Desenvolvimento Produtivo (PDP) para medicamentos entre 2009 e 2020; da Pesquisa Industrial Anual (PIA), do Instituto Brasileiro de Geografia e Estatística (IBGE), entre 1996 e 2018; e os dados da evolução da balança comercial do setor entre 1996 e 2019. Os resultados evidenciam que a agenda do Estado para o setor favoreceu o crescimento da produção de medicamentos genéricos, dos medicamentos isentos de prescrição (MIP) e deu início a alguns projetos de transferência de tecnologia via PDPs para a produção de medicamentos biológicos e sintéticos. Apesar dessa evolução, o Brasil se mantém dependente da importação de insumos químicos e farmacêuticos e de medicamentos acabados. Isto nos mantém em situação de vulnerabilidade tecnológica e econômica em relação aos fornecedores mundiais, além de um aprofundamento do déficit da balança comercial do setor.

Este artículo presenta los resultados de investigación sobre la industria farmacéutica en Brasil, durante el período reciente, realizada en el ámbito del proyecto multicéntrico Complejo Económico-Industrial de la Salud, Innovación y Dinámica Capitalista: Desafíos Estructurales para la Construcción del Sistema Universal de Salud en Brasil. Los cuatro componentes estudiados sobre la evolución de la industria farmacéutica en Brasil fueron: las políticas industriales del Estado; los cambios en la composición financiera y patrimonial de las empresas de capital nacional, la evolución de la producción; y el comportamiento de la balanza comercial. Los análisis tuvieron en consideración el marco teórico propuesto por Luiz Filgueiras y Reinaldo Gonçalves, respecto a la implantación de un "modelo liberal y periférico" en la economía brasileña, a partir del año 1990. Se recabaron y analizaron datos sobre: la situación de las Colaboraciones de Desarrollo Productivo (PDP por su sigla en portugués) para medicamentos entre 2009 y 2020; de la Encuesta Industrial Anual (PIA), del Instituto Brasileño de Geografía y Estadística (IBGE), entre 1996 y 2018; y los datos de la evolución de la balanza comercial del sector entre 1996 y 2019. Los resultados evidencian que la agenda del Estado para el sector favoreció el crecimiento de la producción de medicamentos genéricos, de los medicamentos exentos de prescripción (MIP) y comenzó algunos proyectos de transferencia de tecnología vía PDPs para la producción de medicamentos biológicos y sintéticos. A pesar de esa evolución, Brasil sigue siendo dependiente de la importación de insumos químicos y farmacéuticos y de medicamentos acabados. Esto nos mantiene en una situación de vulnerabilidad tecnológica y económica, en relación con los proveedores mundiales, además de una profundización del déficit de la balanza comercial del sector.

Mudanças recentes e continuidade da dependência tecnológica e econômica na indústria farmacêutica no Brasil / Recent changes and continuity of technological and economic dependency in the pharmaceutical industry in Brazil / Cambios recientes y continuidad de la dependencia tecnológica y económica en la industria farmacéutica en Brasil

Este artigo apresenta os resultados de pesquisa sobre a indústria farmacêutica no Brasil, no período recente, realizada no âmbito do projeto multicêntrico Complexo Econômico-Industrial da Saúde, Inovação e Dinâmica Capitalista: Desafios Estruturais para a Construção do Sistema Universal de Saúde no Brasil. Os quatro componentes estudados sobre a evolução da indústria farmacêutica no Brasil foram: as políticas industriais do Estado; as mudanças na composição financeira e patrimonial das empresas de capital nacional, a evolução da produção; e o comportamento da balança comercial. As análises levaram em consideração o marco teórico proposto por Luiz Filgueiras e Reinaldo Gonçalves a respeito da implantação de um "modelo liberal e periférico" na economia brasileira a partir dos anos 1990. Foram levantados e analisados dados sobre: a situação das Parcerias de Desenvolvimento Produtivo (PDP) para medicamentos entre 2009 e 2020; da Pesquisa Industrial Anual (PIA), do Instituto Brasileiro de Geografia e Estatística (IBGE), entre 1996 e 2018; e os dados da evolução da balança comercial do setor entre 1996 e 2019. Os resultados evidenciam que a agenda do Estado para o setor favoreceu o crescimento da produção de medicamentos genéricos, dos medicamentos isentos de prescrição (MIP) e deu início a alguns projetos de transferência de tecnologia via PDPs para a produção de medicamentos biológicos e sintéticos. Apesar dessa evolução, o Brasil se mantém dependente da importação de insumos químicos e farmacêuticos e de medicamentos acabados. Isto nos mantém em situação de vulnerabilidade tecnológica e econômica em relação aos fornecedores mundiais, além de um aprofundamento do déficit da balança comercial do setor.

This article presents the results of a study on the pharmaceutical industry in Brazil in the recent period, as part of the multicenter project Health Economic-Industrial Complex, Innovation and Capitalist Dynamics: Structural Challenges for Construction of the Universal Health System in Brazil. The four components studied in the evolution of the Brazilian pharmaceutical industry were: State industrial policies; changes in the financial and shareholding composition of companies with domestic capital; trends in production; and trade balance behavior. The analyses considered the theoretical framework proposed by Luiz Filgueiras and Reinaldo Gonçalves concerning the implementation of a "liberal and peripheral model" in the Brazilian economy since the 1990s. Data were collected and analyzed on the situation with the Product Development Partnerships (PDP) for medicines from 2009 to 2020 from the Annual Industrial Survey (PIA) of the Brazilian Institute of Geography and Statistics (IBGE) from 1996 to 2018 and data on the evolution of the sector's trade balance from 1996 to 2019. The results show that the State's agenda for the sector favored the growth in production of generic drugs and over-the-counter drugs and started some technology transfer projects via PDPs for production of biological and synthetic drugs. Despite this evolution, Brazil is still dependent on the importation of chemical and pharmaceutical inputs and finished drugs. This keeps Brazil in a situation of technological and economic vulnerability in relation to global suppliers, besides a growing trade deficit in the sector.

Este artículo presenta los resultados de investigación sobre la industria farmacéutica en Brasil, durante el período reciente, realizada en el ámbito del proyecto multicéntrico Complejo Económico-Industrial de la Salud, Innovación y Dinámica Capitalista: Desafíos Estructurales para la Construcción del Sistema Universal de Salud en Brasil. Los cuatro componentes estudiados sobre la evolución de la industria farmacéutica en Brasil fueron: las políticas industriales del Estado; los cambios en la composición financiera y patrimonial de las empresas de capital nacional, la evolución de la producción; y el comportamiento de la balanza comercial. Los análisis tuvieron en consideración el marco teórico propuesto por Luiz Filgueiras y Reinaldo Gonçalves, respecto a la implantación de un "modelo liberal y periférico" en la economía brasileña, a partir del año 1990. Se recabaron y analizaron datos sobre: la situación de las Colaboraciones de Desarrollo Productivo (PDP por su sigla en portugués) para medicamentos entre 2009 y 2020; de la Encuesta Industrial Anual (PIA), del Instituto Brasileño de Geografía y Estadística (IBGE), entre 1996 y 2018; y los datos de la evolución de la balanza comercial del sector entre 1996 y 2019. Los resultados evidencian que la agenda del Estado para el sector favoreció el crecimiento de la producción de medicamentos genéricos, de los medicamentos exentos de prescripción (MIP) y comenzó algunos proyectos de transferencia de tecnología vía PDPs para la producción de medicamentos biológicos y sintéticos. A pesar de esa evolución, Brasil sigue siendo dependiente de la importación de insumos químicos y farmacéuticos y de medicamentos acabados. Esto nos mantiene en una situación de vulnerabilidad tecnológica y económica, en relación con los proveedores mundiales, además de una profundización del déficit de la balanza comercial del sector.

Dynamics of patents, orphan drug designation, licensing, and revenues from drugs for rare diseases: The market expansion of eculizumab.

BACKGROUND: This study examines the dynamics of the eculizumab patenting, orphan designation, and marketing authorization process in different countries and regulatory systems and analyzes drug revenues since its first marketing authorization. METHODS: A retrospective case study was conducted. Multiple information sources were used to: determine the status of eculizumab patents; examine the designation of orphan drug status by US, European, Japanese, and Brazilian regulatory authorities to determine registration status and approved clinical indications; estimate the prevalence of associated clinical conditions; investigate the history of the drug manufacturer, Alexion Pharmaceuticals, Inc., and its financialized business model; and examine global eculizumab sales revenues since its first marketing authorization. RESULTS: Our search yielded 32 patent families divided into 98 applications. The first patent granted was filed in 1995 by Alexion Pharmaceuticals, Inc. in the US. Eculizumab has always been as an orphan drug, except in the Brazilian regulatory agency. All clinical indications approved thus far refer to rare diseases (e.g., paroxysmal nocturnal hemoglobinuria syndrome, atypical hemolytic-uremic syndrome, refractory and generalized myasthenia gravis, and neuromyelitis optica spectrum disorder). Alexion's revenues amounted to more than US$25 billion between 2007 and 2019, showing a growing trend. Eculizumab led sales from the beginning, being the only product in the company's portfolio until 2015. In 2019, the drug accounted for 79.1% of all revenues. DISCUSSION: Our findings show that a strategy focused on obtaining orphan drug designation, expanding therapeutic indications and the geographic range of marketing approvals, extending monopoly periods, and prioritizing public procurement niches has enhanced revenues and helped the company achieve leadership in a highly specific and profitable market.

Two Hours of Separation Prior to Milking: Is This Strategy Stressful for Jennies and Their Foals?

The goal of this study was to assess whether or not a separation period of 2 h is stressful for jennies and foals, as measured by changes in behaviour, salivary cortisol, and milk production. This study was reviewed and approved by the Committee for the Use and Care of Animals in Research (CEUA) of the School of Veterinary Medicine and Animal Science of the University of São Paulo. Fourteen multiparous Pêga jennies (245 kg average body weight) and their foals were assessed from day 45 to 135 of lactation. Dams and foals were separated for 2 h prior to milking. Behavioural assessments and saliva samples were collected before and after separation, every 15 days, resulting in 14 samples per individual animal. Behavioural states (affiliative and inactivity) and events (agonistic, abnormal, eliminative and vocalisations) of the jennies were observed during 6 min in both periods. Moreover, milk yield was measured. Few significant behavioural and salivary cortisol changes were observed, and milk yield was not affected by cortisol levels in response to the separation. The 2-h separation period, on the basis of the collected variables, did not appear to be stressful for the assessed group of Pêga jennies or foals; however, their ability to adapt to milking routine stress remains to be investigated.

Evaluation of liquid and powdered forms of polyclonal antibody preparation against Streptococcus bovis and Fusobacterium necrophorum in cattle adapted or not adapted to highly fermentable carbohydrate diets.

OBJECTIVE: Feed additives that modify rumen fermentation can be used to prevent metabolic disturbances such as acidosis and optimize beef cattle production. The study evaluated the effects of liquid and powdered forms of polyclonal antibody preparation (PAP) against Streptococcus bovis and Fusobacterium necrophorum on rumen fermentation parameters in ruminally cannulated non-lactating dairy cows that were adapted or unadapted to a high concentrate diet. METHODS: A double 3×3 Latin square design was used with three PAP treatments (control, powdered, and liquid PAP) and two adaptation protocols (adapted, unadapted; applied to the square). Adapted animals were transitioned for 2 weeks from an all-forage to an 80% concentrate diet, while unadapted animals were switched abruptly. RESULTS: Interactions between sampling time and adaptation were observed; 12 h after feeding, the adapted group had lower ruminal pH and greater total short chain fatty acid concentrations than the unadapted group, while the opposite was observed after 24 h. Acetate:propionate ratio, molar proportion of butyrate and ammonia nitrogen concentration were generally greater in adapted than unadapted cattle up to 36 h after feeding. Adaptation promoted 3.5 times the number of Entodinium protozoa but copy numbers of Streptococcus bovis and Fibrobacter succinogens genes in rumen fluid were not affected. However, neither liquid nor powdered forms of PAP altered rumen acidosis variables in adapted or unadapted animals. CONCLUSION: Adaptation of cattle to highly fermentable carbohydrate diets promoted a more stable ruminal environment, but PAP was not effective in this study in which no animal experienced acute or sub-acute rumen acidosis.

The case of eculizumab: litigation and purchases by the Brazilian Ministry of Health.

OBJECTIVES: This study examined the purchases of eculizumab, a high-cost monoclonal antibody used in the treatment of rare diseases by Brazilian federal agencies, in terms of purchased quantities, expenditures, and prices. METHODS: Eculizumab purchases made between March 2007 and December 2018 were analyzed, using secondary data extracted from the Federal Government Purchasing System (SIASG in Portuguese). The following aspects were assessed: number of purchases, purchased quantities, number of daily doses defined per 1,000 inhabitants per year, annual expenditures, and prices. The prices were adjusted by the National Broad Consumer Price Index for December 2018. Linear regression was used for trend analysis. RESULTS: All acquisitions by federal agencies were made by the Brazilian Ministry of Health. The purchases began in 2009 with tender waiver to comply with legal demand. There was an increasing trend in the number of purchases and quantities acquired over time. Two hundred and eighty-three purchases were made, totaling 116,792 units purchased, 28.2% of them in 2018. The adjusted total expenses summed more than R$ 2.44 billion. After market approval by the Brazilian Health Regulatory Agency, the weighted average price fell approximately 35%, to values under the Medicines Market Chamber of Regulation established prices. CONCLUSION: Eculizumab represented extremely significant expenditures for the Brazilian Ministry of Health during the period. All purchases were made to meet demands from lawsuits, outside the competitive environment. The market approval of eculizumab promoted an important price reduction. This study indicates the relevance of licensing and the need for permanent monitoring and auditing of drug purchases to meet legal demands.

The case of eculizumab: litigation and purchases by the Brazilian Ministry of Health / O caso do eculizumabe: judicialização e compras pelo Ministério da Saúde

ABSTRACT OBJECTIVES This study examined the purchases of eculizumab, a high-cost monoclonal antibody used in the treatment of rare diseases by Brazilian federal agencies, in terms of purchased quantities, expenditures, and prices. METHODS Eculizumab purchases made between March 2007 and December 2018 were analyzed, using secondary data extracted from the Federal Government Purchasing System (SIASG in Portuguese). The following aspects were assessed: number of purchases, purchased quantities, number of daily doses defined per 1,000 inhabitants per year, annual expenditures, and prices. The prices were adjusted by the National Broad Consumer Price Index for December 2018. Linear regression was used for trend analysis. RESULTS All acquisitions by federal agencies were made by the Brazilian Ministry of Health. The purchases began in 2009 with tender waiver to comply with legal demand. There was an increasing trend in the number of purchases and quantities acquired over time. Two hundred and eighty-three purchases were made, totaling 116,792 units purchased, 28.2% of them in 2018. The adjusted total expenses summed more than R$ 2.44 billion. After market approval by the Brazilian Health Regulatory Agency, the weighted average price fell approximately 35%, to values under the Medicines Market Chamber of Regulation established prices. CONCLUSION Eculizumab represented extremely significant expenditures for the Brazilian Ministry of Health during the period. All purchases were made to meet demands from lawsuits, outside the competitive environment. The market approval of eculizumab promoted an important price reduction. This study indicates the relevance of licensing and the need for permanent monitoring and auditing of drug purchases to meet legal demands.

RESUMO OBJETIVOS O estudo examinou as aquisições de eculizumabe, um anticorpo monoclonal de alto custo utilizado no tratamento de doenças raras, pelos órgãos federais brasileiros, em termos das quantidades compradas, gastos e preços. MÉTODOS Foram analisadas compras de eculizumabe realizadas entre março de 2007 e dezembro de 2018, por meio de dados secundários extraídos do sistema de compras do governo federal (Siasg). Foram examinados o número de compras, quantidades adquiridas, número de doses diárias definidas por 1.000 habitantes por ano, gastos anuais e preços praticados. Os preços foram corrigidos pelo índice nacional de preços ao consumidor amplo para dezembro de 2018. Regressão linear foi utilizada para análises de tendência. RESULTADOS Todas as aquisições por órgãos federais foram realizadas pelo Ministério da Saúde. As compras se iniciaram em 2009, sendo efetuadas por dispensa de licitação e para atendimento de demanda judicial. Houve tendência crescente no número de compras e quantidades adquiridas ao longo do tempo. Foram realizadas 283 compras, totalizando 116.792 unidades adquiridas, 28,2% compradas em 2018. Os gastos totais contratados corrigidos somaram mais de R$ 2,44 bilhões. Após a aprovação do registro pela Agência Nacional de Vigilância Sanitária, o preço médio ponderado caiu aproximadamente 35%, para valores abaixo dos preços estabelecidos pela Câmara de Regulação do Mercado de Medicamentos. CONCLUSÃO O eculizumabe representou gastos extremamente significativos para o Ministério da Saúde no período. Todas as compras foram feitas para atendimento de demandas judiciais, fora do ambiente competitivo. Seu registro promoveu queda importante nos preços praticados. O estudo aponta a relevância do registro sanitário e da necessidade de monitoramento e auditoria permanentes das compras de medicamentos para atendimento de demandas judiciais.

Mini review on photosensitization by plants in grazing herbivores.

Photosensitization is severe dermatitis or oxidative/chemical changes in the epidermal tissues activated by the light-induced excitation of molecules within the tissue. It is a series of reactions mediated through light receptors and is more common when the plant-produced metabolites are heterocyclic/polyphenols in nature. The areas affected are exposed body parts and mostly non-pigmented areas with least ultraviolet protection. Similarly, cellular alteration also occurs in the affected animal's dermal tissues and body parts and grazing animals by the accumulation and activation of photodynamic molecules. Photo-oxidation can also occur within the plant due to the generation of reactive oxygen species causing damage and degradation in the form of free radicals and DNA. During the last few decades, many new tropical grass species have been introduced in the grazing lands which are genetically modified, and the animals grazing on them are facing various forms of toxicity including photosensitization. The plant's secondary metabolites/drugs may cause toxicity when bacteria, viral agents, fungi (Pithomyces chartarum), or neoplasia injures the liver and prevents the phylloerythrin excretion. All these may disturb the liver enzymes and blood profile causing a decrease in weight and production (wool and milk etc.) with severe dermal, digestive, and nervous problems. Recent advancements in OMICS (cellomics, ethomics, metabolomics, metabonomics, and glycomics) have enabled us to detect and identify the plants' secondary metabolites and changes in the animal's physiology and histopathology as a causative of photosensitivity. The review focuses on types of photosensitization, reasons, secondary metabolic compounds, chemistry, and environmental effect on plants.

A evolução recente da indústria farmacêutica brasileira nos limites da subordinação econômica / The recent evolution of the Brazilian pharmaceutical industry in the limits of economic subordination

Resumo Este artigo apresenta a evolução da indústria farmacêutica brasileira e da balança comercial entre 1996 e 2014 e discute possibilidades de mudanças na política industrial farmacêutica. Os pressupostos da pesquisa foram: que as possibilidades industriais para o setor estão fortemente conectadas com o cenário internacional; e que este piorou a partir dos anos 1990, tornando o país mais vulnerável. As fontes utilizadas foram a Pesquisa Industrial Anual, do Instituto Brasileiro de Geografia Estatística, e os dados da balança comercial do Sistema de Análise das Informações, do Ministério da Indústria, Comércio Exterior e Serviços. Os valores foram deflacionados e corrigidos para desconsiderar a influência da inflação. Os resultados demonstraram que há um desequilíbrio entre a evolução das indústrias farmoquímica e de medicamentos para uso humano em relação à das indústrias voltadas para medicamentos veterinários e de produtos químicos para o agronegócio. A balança comercial mostrou-se crescentemente deficitária para produtos farmacêuticos para uso humano. Os resultados corroboraram tanto a hipótese de crescente subordinação econômica quanto os pressupostos do estudo acima apontados.

Abstract This study shows the results of the development of the Brazilian Pharmaceutical Industry and trade balance between 1996 and 2014, discussing possibilities of changes in Brazilian industrial policies. The research had two assumptions: industrial possibilities are strongly connected with the international scenario, which has worsened since the 1990s, leaving the country more vulnerable. The data sources were the Annual Industrial Survey of the Brazilian Institute of Geography and Statistics and the Foreign Trade Information System from the Ministry of Industry. The values were adjusted not to consider the inflation. The results show that there was a big imbalance between the performances of the human pharmaceutical products and pharmochemical industries in regards to those focused on the production of chemicals and veterinary pharmaceutical products, in favor of these last ones. The trade balance data show a large and growing trade deficit for medicines for human use. The results corroborated the hypothesis of growing international subordination of the Brazilian pharmaceutical industry and the assumptions mentioned above.