RESUMO
Recently, the U.S. Food and Drug Administration (FDA) approved the first oral antiviral drug to treat mild to moderate cases of coronavirus disease. The combination of nirmatrelvir with an already used protease inhibitor class drug, ritonavir, has led to Paxlovid®. Several studies considered drug repositioning as the first trial for new drugs. The precise identification and quantification of polymorphs in raw materials and finished products are important to researchers involved in pharmaceutical development and quality control processes. In this work, we study the solid-state behavior of the antiretroviral drugs ritonavir and lopinavir in raw materials and in milled compositions. The results indicate that mixtures of ritonavir Forms I and II are found in different batches of raw materials from the same manufacturer; besides three equal crystalline samples, an amorphous batch was found in lopinavir. Furthermore, the milling process of the already amorphous lopinavir seems to facilitate the amorphization of ritonavir as well as the production of some unexpected crystalline forms of ritonavir. A phase transition of ritonavir Form I to Form II is only observed when co-milling with amorphous lopinavir. These findings reveal significant variations in phase purity of raw materials that affect the processing and solid-state properties, representing risks for the product quality.
Assuntos
Infecções por Coronavirus , Ritonavir , Humanos , Lopinavir/química , Antivirais , Infecções por Coronavirus/tratamento farmacológico , Combinação de MedicamentosRESUMO
A major challenge to the implementation of artificial photosynthesis (AP), in which fuels are produced from abundant materials (water and carbon dioxide) in an electrochemical cell through the action of sunlight, is the discovery of active, inexpensive, safe, and stable catalysts for the oxygen evolution reaction (OER). Multimetallic molecular catalysts, inspired by the natural photosynthetic enzyme, can provide important guidance for catalyst design, but the necessary mechanistic understanding has been elusive. In particular, fundamental transformations for reactive intermediates are difficult to observe, and well-defined molecular models of such species are highly prone to decomposition by intermolecular aggregation. Here, we present a general strategy for stabilization of the molecular cobalt-oxo cubane core (Co4O4) by immobilizing it as part of metal-organic frameworks, thus preventing intermolecular pathways of catalyst decomposition. These materials retain the OER activity and mechanism of the molecular Co4O4 analog yet demonstrate unprecedented long-term stability at pH 14. The organic linkers of the framework allow for chemical fine-tuning of activity and stability and, perhaps most importantly, provide "matrix isolation" that allows for observation and stabilization of intermediates in the water-splitting pathway.
RESUMO
OBJECTIVE: Evaluate long-term results of autologous pericardial valved conduits in the pulmonary outflow. METHODS: Between June 1983 and October 1993, 82 conduits were placed in the outflow of the venous ventricle. Patients who received homografts (n = 2 patients), heterografts (n = 3 patients), and valveless conduits (n = 19 patients) and those patients who died within 90 days after the operation were excluded. Fifty-four survivors of pulmonary outflow reconstruction with fresh autologous pericardial valved conduits were followed up from 5 to 15 years (mean, 7.47 +/- 2.8 years). Diagnosis include d -transposition of great arteries (n = 16 patients), L -transposition of great arteries (n = 14 patients), tetralogy of Fallot, pulmonary atresia with ventricular septal defect (n = 11 patients), truncus arteriosus (n = 10 patients), and double-outlet ventricle (n = 3 patients). Implantation age ranged from 0.25 to 24 years (mean, 5.2 +/- 4.2 years). Median conduit diameter was 16 mm. Two-dimensional echocardiographic Doppler evaluations were made yearly; 9 patients underwent cardiac catheterization. Reintervention for stenosis was indicated when the pressure gradient exceeded 50 mm Hg. RESULTS: Three late deaths were unrelated to the conduit. Thirty-five autologous pericardial valved conduits increased in diameter (1-7 mm), remained unchanged in 15 patients, and reduced 1 to 2 mm in 4 patients. The median diameter was 18 mm at the last evaluation (P =.0001). Eight patients required conduit-related reoperation 3 to 8 years after the implantation. Two patients underwent balloon dilation of the autologous pericardial valved conduit. No conduit had to be replaced. Freedom from reintervention at 5 and 10 years was 92% and 76%, being 100% at 10 years for conduits larger than 16 mm at time of implantation. CONCLUSIONS: Autologous pericardial valved conduits show excellent long-term results and compare favorably with other conduits.
Assuntos
Cardiopatias Congênitas/cirurgia , Pericárdio/transplante , Valva Pulmonar/cirurgia , Adolescente , Adulto , Criança , Pré-Escolar , Ecocardiografia Doppler , Feminino , Seguimentos , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/mortalidade , Humanos , Lactente , Masculino , Complicações Pós-Operatórias , Reoperação , Estudos Retrospectivos , Inquéritos e Questionários , Taxa de Sobrevida , Transplante Autólogo , Resultado do TratamentoRESUMO
The case of Lysenkoism in the Soviet Union helps us understand how people's wrong beliefs can be influenced by what the information they receive from outside, especially when there is a large volume of media coverage and there is no contrary information to be heard. The population control movement in contemporary United States has many parallels to the Lysenko episode.
PIP: The history of the population control movement in the US resembles the Lysenkoism which destroyed agriculture and the study of genetics in the Soviet Union for 25 years, starting in the 1930s under Stalin's rule. Both movements developed out of only theoretical ideas, with no scientific evidence. Lysenko and Prezent rejected the classical theory by assuming that heredity is a general internal property of living matter. They rejected the gene theory on a priori abstract considerations, ignoring the factual basis of genetics. Likewise, population control advocates adhere to the abstract notion that some unit of discourse is finite, therefore inevitably limiting growth in population and consumption. However, the available evidence does not support the argument that population growth and density are associated with poorer economic results. The case of Lysenkoism in the Soviet Union helps one to understand how people's wrong beliefs can be influenced by what outside information they receive, especially when there is considerable media coverage and no information to the contrary.
Assuntos
Genética Populacional , Dinâmica Populacional , Humanos , Sistemas Políticos , Estados UnidosRESUMO
BACKGROUND: The aim of this study was to evaluate the long-term results of the use of an autologous pericardial valved conduit in the outflow tract of the venous ventricle in congenital heart malformations. METHODS: Fifty-one patients were followed up for a period of 12 to 120 months; 30 for more than 36 months and 13 for more than 72 months. All were evaluated clinically and by two-dimensional and Doppler echocardiography. Eight patients were recatheterized. Postoperative evaluation included serial measurement of pressure gradients and the conduit's diameter at the proximal, valvular, and distal levels. Reoperation because of stenosis was indicated when the gradient across the right ventricular outflow was greater than 50 mm Hg. The reoperation rate in relation with postoperative time, diameter of the autologous pericardial valved conduit at the time of implantation, and malformation was statistically analyzed. RESULTS: In 27 patients the conduit increased its diameter 1 to 7 mm. In 20 patients the diameter remained unchanged, whereas a reduction was noted in 4. Conduit survival free of reoperation for the whole group was 89.9% at 5 years. Conduit survival free of reoperation was 100% at 5 and 7 years for conduits larger than 16 mm at the time of implantation. It was 95% (standard deviation = 4.8%) at 5 years and 72.3% at 7 years for those 16 mm or less. For patients operated after January 1, 1986 (technical modification), conduit survival free of reoperation was 95.4% at 7 years postoperatively. CONCLUSIONS: These results compare favorably with those of other available conduits.
Assuntos
Cardiopatias Congênitas/cirurgia , Pericárdio/transplante , Artéria Pulmonar/cirurgia , Prótese Vascular , Pré-Escolar , Ecocardiografia , Ecocardiografia Doppler , Feminino , Seguimentos , Sobrevivência de Enxerto , Cardiopatias Congênitas/diagnóstico por imagem , Cardiopatias Congênitas/epidemiologia , Humanos , Incidência , Lactente , Masculino , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/epidemiologia , Reoperação , Técnicas de Sutura , Fatores de Tempo , Transplante Autólogo , Obstrução do Fluxo Ventricular Externo/cirurgiaRESUMO
A 3-year-old boy with hepatopulmonary amebiasis treated with chloroquine phosphate for 20 days subsequently was found to have three brain abscesses and responded to prolonged combined therapy with metronidazole and chloroquine phosphate. Cerebral amebiasis should be considered in any patient with amebic dysentery, hepatic abscess, or pulmonary involvement in whom signs or symptoms of central nervous system involvement appear. A prolonged course of appropriate therapy with periodic brain scanning for evidence of improvement is suggested.