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1.
Health Econ Rev ; 14(1): 1, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38165452

RESUMO

Upcoding in Medicare has been a topic of interest to economists and policy makers for nearly 40 years. While upcoding is generally understood as "billing for services at higher level of complexity than the service actually pro- vided or documented," it has a wide range of definitions within the literature. This is largely because the financial incentives across programs and aspects under the coding control of billing specialists and providers are different, and have evolved substantially over time, as has the published literature. Arguably, the primary importance of analyzing upcoding in different parts of Medicare is to inform policy makers on the magnitude of the process and to suggest approaches to mitigate the level of upcoding. Financial estimates for upcoding in traditional Medicare (Medicare Parts A and B), are highly variable, in part reflecting differences in methodology for each of the services covered. To resolve this variability, we used summaries of audit data from the Comprehensive Error Rate Testing program for the period 2010-2019. This program uses the same methodology across all forms of service in Medicare Parts A and B, allowing direct comparisons of upcoding magnitude. On average, upcoding for hospitalization under Part A represents $656 million annually (or 0.53% of total Part A annual expenditures) during our sample period, while up- coding for physician services under Part B is $2.38 billion annually (or 2.43% of Part B annual expenditures). These numbers compare to the recent consistent estimates from multiple different entities putting upcoding in Medicare Part C at $10-15 billion annually (or approximately 2.8-4.2% of Part C annual expenditures). Upcoding for hospitalization under Medicare Part A is small, relative to overall upcoding expenditures.

2.
Am J Med ; 134(11): 1344-1349, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34343514

RESUMO

The emphasis on clinical volume in physician compensation plans has diminished professional vitality in academic medical centers and increased the cost of health care. Physician incentive compensation plans that focus on clinical volume can distort clinical encounters and fail to incorporate the professionalism and intrinsic motivators of clinicians. We assert herein that physician incentive compensation plans should reward clinical value (quality/cost) rather than clinical volume. The recommended change is compelled by the tenets of medical professionalism, the need to cultivate meaning in clinical practice, and the urgent financial and moral imperatives to improve health outcomes and reduce cost. The design of physician incentive compensation plans should incorporate accurate and valid measures of quality and cost, behavioral economic considerations, transparency and equity, prospective assessment of the impact on key outcomes, and flexible elements that encourage innovation and preserve fidelity to unique practice circumstances. Physicians should be recognized in compensation plans for enhancing the value of care, inspiring and educating the future clinical workforce, and improving public health through discovery.


Assuntos
Centros Médicos Acadêmicos , Custos de Cuidados de Saúde , Planos de Incentivos Médicos , Qualidade da Assistência à Saúde , Humanos , Médicos , Profissionalismo
3.
Sci Rep ; 11(1): 7803, 2021 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-33833361

RESUMO

Consumer groups are pressuring modern farmers to be more efficient with a focus on better animal welfare. Herding risks farmer lives, involves stress from farm dogs, and if not performed often and intelligently, risks neglect. We examined the behavioural and physiological response of twelve Dorper sheep (Ovies aries) to a drone to adapt mathematical models of shepherding to the new dimension. The model aims to make it feasible for artificial intelligence to improve the autonomy of farmers and pilots in shepherding from the sky. Sheep acclimatised quickly and positively to the drone initiating drive of a flock, regardless of drone speed. Our results demonstrate that stimulating sheep auditory awareness during herding from the sky leads to varying sheep responses. When controlled, these auditory cues can maintain safer distances between the drone and the sheep, offering great potential for the agriculture industry. We outline our ongoing research plans to achieve more autonomous sky shepherding that is compassionate to animal welfare and trusted by farmers and the consuming public.


Assuntos
Criação de Animais Domésticos/métodos , Bem-Estar do Animal , Inteligência Artificial , Carneiro Doméstico , Animais , Modelos Biológicos , Movimento
4.
J Law Biosci ; 7(1): lsaa032, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32733690

RESUMO

Economic insights are powerful for understanding the challenge of managing a highly infectious disease, such as COVID-19, through behavioral precautions including social distancing. One problem is a form of moral hazard, which arises when some individuals face less personal risk of harm or bear greater personal costs of taking precautions. Without legal intervention, some individuals will see socially risky behaviors as personally less costly than socially beneficial behaviors, a balance that makes those beneficial behaviors unsustainable. For insights, we review health insurance moral hazard, agricultural infectious disease policy, and deterrence theory, but find that classic enforcement strategies of punishing noncompliant people are stymied. One mechanism is for policymakers to indemnify individuals for losses associated with taking those socially desirable behaviors to reduce the spread. We develop a coherent approach for doing so, based on conditional cash payments and precommitments by citizens, which may also be reinforced by social norms.

5.
PLoS One ; 15(4): e0231768, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32302322

RESUMO

CONTEXT: Health policy has long been preoccupied with the problem that health insurance stimulates spending ("moral hazard"). However, much health spending is costly healthcare that uninsured individuals could not otherwise access. Field studies comparing those with more or less insurance cannot disaggregate moral hazard versus access. Moreover, studies of patients consuming routine low-dollar healthcare are not informative for the high-dollar healthcare that drives most of aggregate healthcare spending in the United States. METHODS: We test indemnities as an alternative theory-driven counterfactual. Such conditional cash transfers would maintain an opportunity cost for patients, unlike standard insurance, but also guarantee access to the care. Since indemnities do not exist in U.S. healthcare, we fielded two blinded vignette-based survey experiments with 3,000 respondents, randomized to eight clinical vignettes and three insurance types. Our replication uses a population that is weighted to national demographics on three dimensions. FINDINGS: Most or all of the spending due to insurance would occur even under an indemnity. The waste attributable to moral hazard is undetectable. CONCLUSIONS: For high-cost care, policymakers should be more concerned about the foregone efficient spending for those lacking full insurance, rather than the wasteful spending that occurs with full insurance.


Assuntos
Custos de Cuidados de Saúde , Seguro Saúde , Princípios Morais , Teorema de Bayes , Humanos , Modelos Teóricos , Método de Monte Carlo , Probabilidade
6.
Acad Med ; 93(12): 1827-1832, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30095455

RESUMO

PURPOSE: To identify the factors associated with total Hospital-Acquired Condition Reduction Program (HACRP) score and with receiving a Centers for Medicare and Medicaid Services (CMS) penalty (1% reduction in payment to those hospitals in the lowest-performing quartile of HACRP scores) for fiscal years (FYs) 2015-2017 with a particular focus on trends over this period. METHOD: The authors evaluated the following variables: (1) type of hospital (teaching vs. nonteaching); (2) disproportionate patient percentage; (3) case mix index (CMI); (4) number of staffed beds; (5) length of stay (LOS); (6) gross patient revenue; and (7) region, using data from CMS and the American Hospital Directory. They conducted multivariate linear and logistic regressions. RESULTS: A total of 2,249 hospitals were included. The mean total HACRP scores across hospitals for FY15, FY16, and FY17 were 5.38, 5.35, and 5.18, respectively. In FY15, 21.2% (476/2,249) of hospitals received a penalty compared with 22.6% (508/2,249) in FY16 and 31.3% (704/2,249) in FY17 (P < .001). The logistic regression model showed that teaching hospitals, larger hospitals (> 400 beds), hospitals with high CMI or long LOS, and hospitals in the Northeast and Western United States were more likely to receive a penalty. Teaching hospitals and larger hospitals did not improve their scores over time compared with nonteaching and small hospitals. CONCLUSIONS: A reevaluation of the scoring methodology for the HACRP is needed. CMS could stratify hospitals into homogeneous categories and apply penalties to those that have the worst scores in each category.


Assuntos
Centers for Medicare and Medicaid Services, U.S./organização & administração , Hospitais de Ensino/estatística & dados numéricos , Doença Iatrogênica , Programas Obrigatórios/estatística & dados numéricos , Indicadores de Qualidade em Assistência à Saúde/estatística & dados numéricos , Idoso , Feminino , Hospitais de Ensino/organização & administração , Humanos , Tempo de Internação , Modelos Logísticos , Masculino , Programas Obrigatórios/organização & administração , Avaliação de Programas e Projetos de Saúde , Indicadores de Qualidade em Assistência à Saúde/organização & administração , Estados Unidos
7.
Am J Clin Oncol ; 41(12): 1199-1203, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29672366

RESUMO

OBJECTIVES: Mohs micrographic surgery (MMS) has expanded markedly in recent years but there is limited information on volume, practice patterns or reimbursement. This study characterizes MMS utilization in the Medicare population. MATERIALS AND METHODS: We analyzed the Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File Calendar Year 2013 data set for provider service volume and reimbursement for dermatologists who did and did not perform MMS procedures. RESULTS: Total Medicare-funded MMS procedures increased 25% from 2009 (558,447) to 2013 (700,262). Dermatologists who performed MMS had significantly more average services per provider (5419.4 vs. 3627.1, r=0.16, P<0.0001), were reimbursed significantly more in average total procedure-related compensation ($475,883.64 vs. $144,564.74, r=0.49, P<0.0001) than dermatologists who did not perform MMS, and made up 71.3% of the top decile of dermatologists ranked by total reimbursement received from Medicare. Total MMS service volume and reimbursement was concentrated among a subset of providers. Among MMS providers, a higher volume of MMS procedures was correlated with a greater likelihood of performing procedures on lesions located on the trunk, arms or legs (r=0.27, P<0.001). CONCLUSIONS: In 2013 reimbursement for MMS comprised almost 19% of the amount reimbursed by Medicare Part B Fee For Service to dermatologists and greater than half a percent of the total amount reimbursed to all physicians participating in the program. Further studies incorporating clinical and outcomes data are needed to evaluate appropriate utilization of this procedure.


Assuntos
Dermatologistas/economia , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Medicare/economia , Medicare/estatística & dados numéricos , Cirurgia de Mohs/estatística & dados numéricos , Padrões de Prática Médica , Mecanismo de Reembolso , Neoplasias Cutâneas/cirurgia , Humanos , Cirurgia de Mohs/economia , Cirurgia de Mohs/métodos , Neoplasias Cutâneas/economia , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/patologia , Estados Unidos
8.
Artigo em Inglês | MEDLINE | ID: mdl-26765559

RESUMO

Adults living with congenital heart disease (CHD) now outnumber children with the disease. Thanks to medical advances over the past 75 years, many of these fatal childhood heart problems have changed to chronic medical conditions. As the population of adults with CHD increases, they will require increasingly complex medical, surgical and catheter-based therapies. In addition, social burdens including education, employment and insurability, which increase the societal costs of adult CHD, are now being recognized for adults living with CHD. This review summarizes the available literature on the economics of adult CHD.


Assuntos
Efeitos Psicossociais da Doença , Atenção à Saúde/economia , Cardiopatias Congênitas/economia , Adulto , Doença Crônica , Atenção à Saúde/métodos , Emprego/economia , Cardiopatias Congênitas/epidemiologia , Cardiopatias Congênitas/terapia , Humanos
10.
PLoS One ; 7(12): e51773, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23272165

RESUMO

Present on the plasma membrane of most metazoans, caveolae are specialized microdomains implicated in several endocytic and trafficking mechanisms. Caveolins and the more recently discovered cavins are the major protein components of caveolae. Previous studies reported that caveolar invaginations can be induced de novo on the surface of caveolae-negative mammalian cells upon heterologous expression of caveolin-1. However, it remains undocumented whether other components in the transfected cells participate in caveolae formation. To address this issue, we have exploited the protozoan Toxoplasma as a heterologous expression system to provide insights into the minimal requirements for caveogenesis and caveolar endocytosis. Upon expression of caveolin-1, Toxoplasma accumulates prototypical exocytic caveolae 'precursors' in the cytoplasm. Toxoplasma expressing caveolin-1 alone, or in conjunction with cavin-1, neither develops surface-located caveolae nor internalizes caveolar ligands. These data suggest that the formation of functional caveolae at the plasma membrane in Toxoplasma and, by inference in all non-mammalian cells, requires effectors other than caveolin-1 and cavin-1. Interestingly, Toxoplasma co-expressing caveolin-1 and cavin-1 displays an impressive spiraled network of membranes containing the two proteins, in the cytoplasm. This suggests a synergistic activity of caveolin-1 and cavin-1 in the morphogenesis and remodeling of membranes, as illustrated for Toxoplasma.


Assuntos
Cavéolas/metabolismo , Endocitose , Toxoplasma/metabolismo , Animais , Animais Geneticamente Modificados , Caveolina 1/genética , Caveolina 1/metabolismo , Linhagem Celular , Membrana Celular/metabolismo , Núcleo Celular/metabolismo , Vesículas Citoplasmáticas/metabolismo , Expressão Gênica , Complexo de Golgi/metabolismo , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Transporte Proteico , Toxoplasma/genética
11.
Acad Med ; 87(2): 230-5, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22273616

RESUMO

Key Indicators in Academic Medicine (KIAMs), a new feature in Academic Medicine, are intended to substantially inform teaching hospitals and medical schools on those metrics that may best gauge their health, including the performance of units and programs within these organizations. Ultimately, KIAMs may promote effective growth and development in a dynamic clinical, training, and research environment. At the outset of this laudable feature, the authors of this perspective offer a suggested framework for analyzing key indicators with the goal of enhancing the usefulness of the published KIAMs. They outline their view of pitfalls and opportunities in the development of key indicators and suggest strategies. The authors close by suggesting how this feature could form the framework for a comprehensive national project.


Assuntos
Competência Clínica , Currículo/normas , Educação Médica/métodos , Educação Médica/normas , Humanos , Desenvolvimento de Programas , Avaliação de Programas e Projetos de Saúde , Alocação de Recursos , Faculdades de Medicina/organização & administração
12.
Acad Med ; 86(9): 1084-92, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21785307

RESUMO

Optimizing resource allocation is essential for effective academic health center (AHC) management, yet guidelines and principles for doing so in the research and educational arenas remain limited. To address this issue, the authors analyzed responses to the 2007-2008 Association of Academic Health Centers census using ratio analysis. The concept was to normalize data from an individual institution to that same institution, by creating a ratio of two separate values from the institution (e.g., total faculty FTEs/total FTEs). The ratios were then compared across institutions. Generally, this strategy minimizes the effect of institution size on the responses, size being the predominant limitation of using absolute values for developing meaningful metrics. In so doing, ratio analysis provides a range of responses that can be displayed in graphical form to determine the range and distribution of values. The data can then be readily scrutinized to determine where any given institution falls within the distribution. Staffing ratios and operating ratios from up to 54 institutions are reported. For ratios including faculty numbers in the numerator or denominator, the range of values is wide and minimally discriminatory, reflecting heterogeneity across institutions in faculty definitions. Values for financial ratios, in particular total payroll expense/total operating expense, are more tightly clustered, reflecting in part the use of units with a uniform definition (i.e., dollars), and emphasizing the utility of such ratios in decision guidelines. The authors describe how to apply these insights to develop metrics for resource allocation in the research and educational arenas.


Assuntos
Centros Médicos Acadêmicos/economia , Docentes de Medicina/estatística & dados numéricos , Alocação de Recursos/economia , Centros Médicos Acadêmicos/organização & administração , Eficiência Organizacional , Inquéritos Epidemiológicos , Humanos , Alocação de Recursos/estatística & dados numéricos
13.
Mol Microbiol ; 76(5): 1232-49, 2010 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-20487267

RESUMO

Toxoplasma is a protozoan parasite proficiently adapted to thrive in a parasitophorous vacuole (PV) formed in the cytoplasm of a large variety of mammalian cells. As an actively dividing organism, the parasite must adjust the lipid composition of its membranes to preserve organelle vitality and expand the size of the PV membrane to accommodate growing progeny. We showed that Toxoplasma takes up host lipids and can expel major lipids in an ATP-dependent process. In order to provide detailed mechanistic insights into lipid trafficking phenomena relevant to Toxoplasma biology, we characterized six parasite ATP-binding cassette (ABC) G family transporters and investigated their potential contribution to lipid homeostatic processes. All these transporters are expressed in the parasite and five of them are upregulated upon exposure to sterols. Four ABCG are localized to secretory organelles and the plasma membrane, and promote cholesterol and phospholipid efflux, reflecting the importance in exportation of large amounts of lipids into the PV. Interestingly, one ABCG that is associated with vesicles in the PV and the plasma membrane acts as a cholesterol importer. This last finding expands our current view on the role of some ABCG transporters in eukaryotic sterol influx.


Assuntos
Transportadores de Cassetes de Ligação de ATP/metabolismo , Metabolismo dos Lipídeos , Isoformas de Proteínas/metabolismo , Proteínas de Protozoários/metabolismo , Toxoplasma/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Sequência de Aminoácidos , Animais , Transporte Biológico/fisiologia , Células COS , Membrana Celular/química , Membrana Celular/metabolismo , Chlorocebus aethiops , Interações Hospedeiro-Parasita , Humanos , Dados de Sequência Molecular , Organismos Geneticamente Modificados , Fosfolipídeos/metabolismo , Isoformas de Proteínas/genética , Proteínas de Protozoários/genética , Alinhamento de Sequência , Esteróis/metabolismo , Toxoplasma/citologia , Toxoplasma/genética
14.
Acad Med ; 84(11): 1482-4, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19858795

RESUMO

Academic institutions must have strategies for evaluating research productivity by faculty. Such strategies are useful in guiding resource allocations for the research enterprise, for decisions on faculty promotions, and for broader institutional planning, including program development. Commonly, decisions about research space utilization, and funding to support the space, are considered within the purview of the institutional administration. Peer review, in manuscript and grant submissions and the promotions process, is more commonly used to evaluate the impact of faculty research. The article by Iyengar et al in this issue of Academic Medicine takes an interesting approach to evaluate research productivity of individual faculty by integrating benchmarks for research funding and publication impact. The strategy of using these benchmarks to partition faculty into quadrants to guide faculty development activities is clever and useful. Less clear are the philosophy and long-term utility of the approach. The applicability to the stated goal of promoting multidisciplinary and interdisciplinary translational research is not obvious, nor is it apparent that faculty will continue to view decisions as transparent and fair over the longer term. Nevertheless, the authors' article is a welcome contribution at a time when many institutions are struggling with issues of evaluating faculty investigators and allocating resources for research.


Assuntos
Pesquisa Biomédica , Eficiência Organizacional , Eficiência , Docentes de Medicina , Humanos , Competência Profissional
15.
Acad Med ; 84(1): 13-25, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19116472

RESUMO

Construction of new biomedical research facilities has outpaced the funding sources for faculty to occupy those facilities. This puts a premium on the efficient allocation of central resources for faculty recruitment. The author developed a mathematical model to determine the optimal structure (dollars, space) for allocating resource packages when recruiting new faculty, based on expected financial returns from those faculty. Surprisingly, the optimal strategy was to allocate homogeneous recruitment packages, independent of the recruited faculty member's rank or the individual's expected revenue generation. Optimization results were used to allocate recruitment packages to new department head and center directors in the University of Arizona College of Medicine during the last four years (2005-2008). At any institution that uses this model, appropriate distribution of facilities and administrative revenues at the institution is needed to equitably balance the costs and benefits associated with faculty expansion.


Assuntos
Pesquisa Biomédica/organização & administração , Docentes de Medicina/estatística & dados numéricos , Modelos Organizacionais , Alocação de Recursos/organização & administração , Faculdades de Medicina , Humanos , Estados Unidos , Recursos Humanos
16.
Acad Med ; 83(9): 837-44, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18728439

RESUMO

The authors describe initiatives at the University of Arizona College of Medicine to markedly expand faculty, build research along programmatic lines, and promote a new, highly integrated medical school curriculum. Accomplishing these goals in this era of declining resources is challenging. The authors describe their approaches and outcomes to date, derived from a solid theoretical framework in the management literature, to (1) support research faculty recruitment, emphasizing return on investment, by using net present value to guide formulation of recruitment packages, (2) stimulate efficiency and growth through incentive plans, by using utility theory to optimize incentive plan design, (3) distribute resources to support programmatic growth, by allocating research space and recruitment dollars to maximize joint hires between units with shared interests, and (4) distribute resources from central administration to encourage medical student teaching, by aligning state dollars to support a new integrated organ-system based-curriculum. Detailed measurement is followed by application of management principles, including mathematical modeling, to make projections based on the data collected. Although each of the initiatives was developed separately, they are linked functionally and financially, and they are predicated on explicitly identifying opportunity costs for all major decisions, to achieve efficiencies while supporting growth. The overall intent is to align institutional goals in education, research, and clinical care with incentives for unit heads and individual faculty to achieve those goals, and to create a clear line of sight between expectations and rewards. Implementation is occurring in a hypothesis-driven fashion, permitting testing and refinement of the strategies.


Assuntos
Centros Médicos Acadêmicos/economia , Centros Médicos Acadêmicos/organização & administração , Seleção de Pessoal/economia , Apoio à Pesquisa como Assunto/economia , Arizona , Currículo , Humanos , Inovação Organizacional/economia , Objetivos Organizacionais/economia
17.
Acad Med ; 83(3): 207-16, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18316864

RESUMO

In FY04, the authors developed and implemented models to manage existing and incremental research space, and to facilitate programmatic research, at the University of Arizona College of Medicine. Benchmarks were set for recovery of total sponsored research dollars and for facilities and administrative (F&A) dollars/net square foot (nsf) of space, based on college-wide metrics. Benchmarks were applied to units (departments, centers), rather than to individual faculty. Performance relative to the benchmark was assessed using three-year moving averages, and applied to existing blocks of space. Space was recaptured or allocated, in all cases to programmatic themes, using uniform policies. F&A revenues were returned on the basis of performance relative to a benchmark. During the first two years after implementation of the model (FY05 and FY06), and for the 24 units occupying research space, median total sponsored research revenue/nsf increased from $393.96 to $474.46 (20.4%), and median F&A revenue/nsf increased from $57.42 to $91.86 (60.0%). These large increases in median values are driven primarily from redistribution and recapturing of space. Recruiting policies for unit heads were developed to facilitate joint hires among units. In combination, these policies created a comprehensive space management model for facilitating programmatic research. Although challenges remain in implementing the programmatic recruitment strategy, and selected modifications to the original policy were introduced later (e.g., research space for newly recruited junior faculty is now exempted from calculations for three years), overall, the models have created a climate of transparency that is now accepted and that allows efficient and equitable management of research space.


Assuntos
Arquitetura , Organização do Financiamento , Hospitais Universitários/organização & administração , Objetivos Organizacionais , Arizona , Custos e Análise de Custo , Hospitais Universitários/economia , Humanos , Modelos Econômicos , Faculdades de Medicina/economia , Faculdades de Medicina/organização & administração
18.
Antimicrob Agents Chemother ; 52(5): 1840-2, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18316523

RESUMO

The effects of quinoline antimalarials on endocytosis by Plasmodium falciparum was investigated by measuring parasite hemoglobin levels, peroxidase uptake, and transport vesicle content. Mefloquine, quinine, and halofantrine inhibited endocytosis, and chloroquine inhibited vesicle trafficking, while amodiaquine shared both effects. Protease inhibitors moderated hemoglobin perturbations, suggesting a common role for heme binding.


Assuntos
Antimaláricos/farmacologia , Endocitose/efeitos dos fármacos , Plasmodium falciparum/efeitos dos fármacos , Quinolinas/farmacologia , Amodiaquina/farmacologia , Animais , Western Blotting , Cloroquina/farmacologia , Eritrócitos/parasitologia , Hemoglobinas/metabolismo , Humanos , Mefloquina/farmacologia , Peroxidase/metabolismo , Fenantrenos/farmacologia , Plasmodium falciparum/citologia , Plasmodium falciparum/metabolismo , Ligação Proteica/efeitos dos fármacos , Proteínas de Protozoários/metabolismo
19.
Proc Natl Acad Sci U S A ; 105(7): 2463-8, 2008 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-18263733

RESUMO

During the bloodstage of malaria infection, the parasite internalizes and degrades massive amounts of hemoglobin from the host red blood cell. Using serial thin-section electron microscopy and three-dimensional reconstruction, we demonstrate four independent, but partially overlapping, hemoglobin-uptake processes distinguishable temporally, morphologically, and pharmacologically. Early ring-stage parasites undergo a profound morphological transformation in which they fold, like a cup, onto themselves and in so doing take a large first gulp of host cell cytoplasm. This event, which we term the "Big Gulp," appears to be independent of actin polymerization and marks the first step in biogenesis of the parasite's lysosomal compartment-the food vacuole. A second, previously identified uptake process, uses the cytostome, a well characterized and morphologically distinct structure at the surface of the parasite. This process is more akin to classical endocytosis, giving rise to small (<0.004 fl) vesicles that are marked by the early endosomal regulatory protein Rab5a. A third process, also arising from cytostomes, creates long thin tubes previously termed cytostomal tubes in an actin-dependent manner. The fourth pathway, which we term phagotrophy, is similar to the Big Gulp in that it more closely resembles phagocytosis, except that phagotrophy does not require actin polymerization. Each of these four processes has aspects that are unique to Plasmodium, thus opening avenues to antimalarial therapy.


Assuntos
Hemoglobinas/metabolismo , Malária/parasitologia , Plasmodium falciparum/metabolismo , Actinas/metabolismo , Animais , Hemoglobinas/ultraestrutura , Microscopia Imunoeletrônica , Plasmodium falciparum/ultraestrutura , Esquizontes/ultraestrutura , Trofozoítos/ultraestrutura , Vacúolos/ultraestrutura , Proteínas rab5 de Ligação ao GTP/metabolismo
20.
Cell Microbiol ; 10(2): 452-64, 2008 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17944961

RESUMO

The intra-erythrocytic stages of the malaria parasite endocytose large quantities of the surrounding erythrocyte cytoplasm and deliver it to a digestive food vacuole via endocytic vesicles. Digestion provides amino acids for parasite protein synthesis and is required to maintain the osmotic integrity of the host cell. The parasite endocytic pathway has been described morphologically by electron microscopy, but the molecular mechanisms that mediate and regulate it remain elusive. Given the involvement of actin in endocytosis in other eukaryotes, we have used actin inhibitors to assess the requirement for this protein in the endocytic pathway of the human malaria parasite, Plasmodium falciparum. Treatment of cultures with cytochalasin D did not affect haemoglobin levels in the parasites when co-administered with protease inhibitors, and neither did it affect the uptake of the endocytic tracer horseradish peroxidase, suggesting the absence of actin in the mechanism of endocytosis. However, in the absence of protease inhibitors, treated parasites contained increased levels of haemoglobin due to an accumulation of enlarged endocytic vesicles, as determined by immunofluorescence and electron microscopy, suggesting a role for actin in vesicle trafficking, possibly by mediating vesicle maturation and/or fusion to the digestive vacuole. In contrast to cytochalasin D, treatment with jasplakinolide led to an inhibition of endocytosis, an accumulation of vesicles closer to the plasma membrane and a marked concentration of actin in the parasite cortex. We propose that the stabilization of cortical actin filaments by jasplakinolide interferes with normal endocytic vesicle formation and migration from the cell periphery.


Assuntos
Actinas/fisiologia , Endocitose/fisiologia , Plasmodium falciparum/metabolismo , Citoesqueleto de Actina/efeitos dos fármacos , Citoesqueleto de Actina/metabolismo , Citoesqueleto de Actina/fisiologia , Actinas/antagonistas & inibidores , Actinas/metabolismo , Animais , Transporte Biológico/fisiologia , Células Cultivadas , Citocalasina D/farmacologia , Depsipeptídeos/farmacologia , Endocitose/efeitos dos fármacos , Eritrócitos/parasitologia , Eritrócitos/ultraestrutura , Hemoglobinas/metabolismo , Humanos , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Plasmodium falciparum/efeitos dos fármacos , Plasmodium falciparum/ultraestrutura , Inibidores de Proteases/farmacologia , Vesículas Transportadoras/metabolismo , Vesículas Transportadoras/fisiologia , Vesículas Transportadoras/ultraestrutura
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