LA ADMINISTRACIÓN DEL EFECTIVO Y EL CRÉDITO COMERCIAL: IMPACTO EN EL CAPITAL DE TRABAJO / THE MANAGEMENT OF CASH AND TRADE CREDIT: IMPACT ON WORKING CAPITAL

El estudio de la gestión financiera del efectivo y el crédito comercial constituye una importante función del financista en la empresa estatal socialista. Desafortunadamente en muchas ocasiones, el financiero está al margen de la toma de decisiones claves para el funcionamiento de la empresa. En función de la reflexión anterior fue realizado el presente trabajo, que abarca los años 2021-2022. El mismo tiene como el objetivo aplicar un procedimiento financiero a través de la utilización de los métodos y técnicas de análisis financiero para la medición del impacto de la administración del efectivo y el crédito comercial en el capital de trabajo. Para lograr este objetivo fue utilizada la información reflejada en los Estados Financieros, la documentación que reflejan la antigüedad de las cuentas por cobrar y pagar, los expedientes por clientes y contratos de compra venta de una empresa estatal. Los resultados alcanzados al aplicar el procedimiento, a partir de las técnicas de análisis financiero indican que la empresa opera con capital de trabajo positivo, incapacidad de pago para cumplir las obligaciones a corto plazo con su partida más líquida efectivo y deficiencias en la administración del crédito comercial; con saldos envejecidos cuentas por cobrar y pagar, que indican deficiencias en las políticas de cobros y pagos. Estos resultados reflejan un impacto perjudicial en el manejo de estas partidas en la administración del capital de trabajo de la empresa. El procedimiento permite dotar a los directivos de información precisa para fortalecer la toma de decisiones

Novel S-adenosyl-L-methionine decarboxylase inhibitors as potent antiproliferative agents against intraerythrocytic Plasmodium falciparum parasites

S-adenosyl-L-methionine decarboxylase (AdoMetDC) in the polyamine biosynthesis pathway has been identified as a suitable drug target in Plasmodium falciparum parasites, which causes the most lethal form of malaria. Derivatives of an irreversible inhibitor of this enzyme, 50-{[(Z)-4-amino-2-butenyl]methylamino}- 50-deoxyadenosine (MDL73811), have been developed with improved pharmacokinetic profiles and activity against related parasites, Trypanosoma brucei. Here, these derivatives were assayed for inhibition of AdoMetDC from P. falciparum parasites and the methylated derivative, 8-methyl-50-{[(Z)- 4-aminobut-2-enyl]methylamino}-50-deoxyadenosine (Genz-644131) was shown to be the most active. The in vitro efficacy of Genz-644131 was markedly increased by nanoencapsulation in immunoliposomes, which specifically targeted intraerythrocytic P. falciparum parasites.Department of Science and Technology through the South African Malaria Initiative, the University of Pretoria, the South African National Research Foundation and by grant BIO2011-25039 from the Ministerio de Economía y Competitividad, Spain, which included FEDER funds, and 2009SGR-760 from the Generalitat de Catalunya, Spainhttp://www.elsevier.com/locate/ijpddrhb201

The glutathione biosynthetic pathway of Plasmodium is essential for mosquito transmission

1Infection of red blood cells (RBC) subjects the malaria parasite to oxidative stress. Therefore, efficient antioxidant and redox systems are required to prevent damage by reactive oxygen species. Plasmodium spp. have thioredoxin and glutathione (GSH) systems that are thought to play a major role as antioxidants during blood stage infection. In this report, we analyzed a critical component of the GSH biosynthesis pathway using reverse genetics. Plasmodium berghei parasites lacking expression of gamma-glutamylcysteine synthetase (γ-GCS), the rate limiting enzyme in de novo synthesis of GSH, were generated through targeted gene disruption thus demonstrating, quite unexpectedly, that γ-GCS is not essential for blood stage development. Despite a significant reduction in GSH levels, blood stage forms of pbggcs− parasites showed only a defect in growth as compared to wild type. In contrast, a dramatic effect on development of the parasites in the mosquito was observed. Infection of mosquitoes with pbggcs− parasites resulted in reduced numbers of stunted oocysts that did not produce sporozoites. These results have important implications for the design of drugs aiming at interfering with the GSH redox-system in blood stages and demonstrate that de novo synthesis of GSH is pivotal for development of Plasmodium in the mosquito

Association of Plasmodium falciparum with Human Endothelial Cells in vitro.

Endothelial abnormalities play a critical role in the pathogenesis of malaria caused by the human pathogen, Plasmodium falciparum. In serious infections and especially in cerebral malaria, red blood cells infected with the parasite are sequestered in small venules in various organs, resulting in endothelial activation and vascular occlusion, which are believed to be largely responsible for the morbidity and mortality caused by this infection, especially in children. We demonstrate that after incubation with infected red blood cells (iRBCs), cultured human umbilical vein endothelial cells (HUVECs) contain parasite protein, genomic DNA, and RNA, as well as intracellular vacuoles with apparent parasite-derived material, but not engulfed or adherent iRBCs. The association of this material with the HUVECs is observed over 96 hours after removal of iRBCs. This phenomenon may occur in endothelial cells in vivo by the process of trogocytosis, in which transfer of material between cells depends on direct cell contact. This process may contribute to the endothelial activation and disruption involved in the pathogenesis of cerebral malaria

Marvels and Shadows: Science and Education at the University of Puerto Rico School of Tropical Medicine under the Auspices of Columbia University: An Introduction

This essay introduces a series of five historical articles on the scientific and educational contributions of the University of Puerto Rico School of Tropical Medicine (STM), under the auspices of Columbia University (1926-1949), to the fields of tropical medicine and public health. The articles will appear in several consecutive issues, and will address various themes as follows: 1) historical antecedents of the STM, particularly institutional precedents; 2) the educational legacy of the STM; 3) a history of the STM scientific journal ( The Puerto Rico Journal of Public Health and Tropical Medicine ); 4) the scientific practices and representations that prevailed at the institution; and, 5) a brief sociocultural history of malaria in Puerto Rico, mainly from the perspective of the STM\u27s scientific and public health activities. The authors have systematically and comprehensively studied a wide variety of documents from different sources based on multiple archives in Puerto Rico, the United States and England. The authors treat the fluid meanings of the examined historical encounters from a research perspective that privilege complex reciprocal interactions, multiple adaptations and elaborate sociocultural constructs present in a collaborative exemplar of the modernity of medical science in a neocolonial tropical context

Implications of Glutathione Levels in the Plasmodium berghei Response to Chloroquine and Artemisinin.

Malaria is one of the most devastating parasitic diseases worldwide. Plasmodium drug resistance remains a major challenge to malaria control and has led to the re-emergence of the disease. Chloroquine (CQ) and artemisinin (ART) are thought to exert their anti-malarial activity inducing cytotoxicity in the parasite by blocking heme degradation (for CQ) and increasing oxidative stress. Besides the contribution of the CQ resistance transporter (PfCRT) and the multidrug resistant gene (pfmdr), CQ resistance has also been associated with increased parasite glutathione (GSH) levels. ART resistance was recently shown to be associated with mutations in the K13-propeller protein. To analyze the role of GSH levels in CQ and ART resistance, we generated transgenic Plasmodium berghei parasites either deficient in or overexpressing the gamma-glutamylcysteine synthetase gene (pbggcs) encoding the rate-limiting enzyme in GSH biosynthesis. These lines produce either lower (pbggcs-ko) or higher (pbggcs-oe) levels of GSH than wild type parasites. In addition, GSH levels were determined in P. berghei parasites resistant to CQ and mefloquine (MQ). Increased GSH levels were detected in both, CQ and MQ resistant parasites, when compared to the parental sensitive clone. Sensitivity to CQ and ART remained unaltered in both pgggcs-ko and pbggcs-oe parasites when tested in a 4 days drug suppressive assay. However, recrudescence assays after the parasites have been exposed to a sub-lethal dose of ART showed that parasites with low levels of GSH are more sensitive to ART treatment. These results suggest that GSH levels influence Plasmodium berghei response to ART treatment

Total GSH levels in blood stages of <i>P</i>. <i>berghei</i> parasites.

<p>GSH levels were determined by HPLC in extracts of purified blood stage <i>P</i>. <i>berghei</i> parasites obtained from asynchronous infections of <b>(A)</b> ANKA wild type, <i>pbggcs-oe1</i> and <i>pbggcs-oe2</i>, <b>(B)</b> N clone (drug sensitive), RC (selected for CLQ resistant) and N/1100 (selected for MFQ resistant) parasites. GSH concentration was significantly increased in the <i>pbggcs-oe</i> parasites as compared to ANKA wild type. Similarly, the drug resistant lines RC and N/1100 displayed significantly higher GSH levels as compared to the sensitive one (N clone). Numbers on boxes represent the mean concentration of GSH. Asterisks denote significant changes in GSH concentration as determined by a One-way ANOVA with Tukey’s Multiple Comparison Test (* = P<0.05, ** = P<0.001).</p

Drug response curves to CLQ and ART.

<p>Dose response curves show percent growth for each parasite clone relative to the untreated control on day 4 of the assay (5^th day post infection) versus drug concentration. The 4-day suppressive test was carried out for CLQ (A and C) and ART (B and D) on two independent <i>pbggcs-ko</i> (<i>pbggcs-ko1; pbggcs-ko2</i>) and <i>pbggcs</i>-oe (<i>pbggcs-oe1; pbggcs-oe2</i>) clones. To compare the drug responses from the mutant parasites, the parasitemia from each parasite line was normalized to the parasitemia of the untreated control. No significant differences in the EC₅₀ values were observed between parasites with the <i>pbggcs</i> gene silenced or overexpressed as compared to wild type control. Bars represent standard deviation of the mean.</p