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INTRODUCTION: New personal hemodialysis systems, such as the quanta SC+, are being developed; these systems are smaller and simpler to use while providing the clearances of conventional systems. Increasing the uptake of lower-intensity assistance and full self-care dialysis may provide economic benefits to the public health payer. In the United Kingdom, most hemodialysis patients currently receive facility-based dialysis costing more than £36,350 per year including patient transport. As such, we aimed to describe the annual costs of using the SC+ hemodialysis system in the United Kingdom for 3×-weekly and 3.5×-weekly dialysis regimens, for self-care hemodialysis provided both in-center and at home. METHODS: We applied a cost minimization approach. Costs for human resources, equipment, and consumables were sourced from the dialysis machine developer (Quanta Dialysis Technologies) based upon discussions with dialysis providers. Facility overhead expenses and transport costs were taken from a review of the literature. FINDINGS: Annual costs associated with the use of the SC+ hemodialysis system were estimated to be £26,642 for hemodialysis provided 3× weekly as home self-care; £30,235 for hemodialysis provided 3× weekly as self-care in-center; £29,866 for hemodialysis provided 3.5× weekly as home self-care; and £36,185 for hemodialysis provided 3.5× weekly as self-care in-center. DISCUSSION: We found that the SC+ hemodialysis system offers improved cost-effectiveness for both 3×-weekly and 3.5×-weekly self-care dialysis performed at home or as self-care in-center versus fully assisted dialysis provided 3× weekly with conventional machines in facilities.
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Fallo Renal Crónico , Diálisis Peritoneal , Análisis Costo-Beneficio , Hemodiálisis en el Domicilio , Humanos , Fallo Renal Crónico/terapia , Diálisis Renal , AutocuidadoRESUMEN
INTRODUCTION: Interventions that increase physical activity behavior can reduce morbidity and prolong life, but long-term effects in large populations are unproven. This study investigates the association of medical fitness facility membership and frequency of attendance with all-cause mortality and rate of hospitalization. METHODS: A propensity weighted retrospective cohort study was conducted by linking individuals who attended medical fitness facilities in Winnipeg, Canada to provincial health administrative databases. Members aged ≥18 years who had ≥1 year of provincial health coverage from their index date between January 1, 2005 and December 31, 2015 were included. Controls were assigned a pseudo-index date at random on the basis of the frequency distribution of index dates in the intervention group. Members were stratified into low-frequency attenders (<1 weekly visit), moderate-frequency attenders (1-3 weekly visits), and high-frequency attenders (>3 weekly visits). The primary outcomes were time to all-cause mortality and rate of hospitalizations. Statistical analyses were performed between 2018 and 2020. RESULTS: Among 19,300 adult members and 515,810 controls, members had a 60% lower risk of all-cause mortality during the first 651 days and 48% after 651 days. Membership was associated with a 13% lower risk of hospitalizations. A dose-response effect was apparent because higher weekly attendance was associated with a lower risk of hospitalizations (low frequency: 9%, moderate frequency: 20%, high frequency: 39%). CONCLUSIONS: Membership at a medical fitness facility was associated with a reduced risk of all-cause mortality and hospitalizations. Healthcare systems should consider the medical fitness model as a preventative public health strategy to encourage physical activity participation.
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Ejercicio Físico , Hospitalización , Adolescente , Adulto , Instituciones de Salud , Humanos , Evaluación de Resultado en la Atención de Salud , Estudios RetrospectivosRESUMEN
BACKGROUND AND OBJECTIVES: Frailty is common in patients with CKD. Little is known about the prevalence of frailty and its effect on prognosis and decisions surrounding dialysis modalities in patients with advanced CKD (eGFR<30 ml/min per 1.73 m2). Our objective was to determine the agreement between different frailty measures and physical function and their association with dialysis modality choice (home based versus in-center) and all-cause mortality in patients with advanced CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our study was a prospective, multicenter, cohort study. In 603 patients with advanced CKD, we collected demographics, comorbidities, and laboratory results in addition to objective (Fried frailty criteria) and subjective measures of frailty (physician and nurse impressions) and physical function (Short Physical Performance Battery). Logistic regression and Cox proportional hazards models were used to evaluate the association of frailty with dialysis modality choice and all-cause mortality, respectively. RESULTS: The prevalence of frailty varied with assessment tool used (Fried frailty criteria, 34%; Short Physical Performance Battery, 55%; physician impression, 44%; nurse impression, 36%). The agreement between all frailty and physical function measures was poor. We had 227 patients reach kidney failure and decide on a dialysis therapy, and 226 patients died during a mean follow-up of 1455 days. After adjusting for age, sex, and comorbid conditions, the Fried criteria and Short Physical Performance Battery were associated with a two-fold higher risk of all-cause mortality (hazard ratio, 1.96; 95% confidence interval, 1.47 to 2.61 and hazard ratio, 1.96; 95% confidence interval,1.42 to 2.76, respectively). Patients deemed as frail by physician and nurse frailty impressions were three to four times more likely to choose in-center dialysis (odds ratio, 3.41; 95% confidence interval, 1.56 to 7.44; odds ratio, 3.87; 95% confidence interval, 1.76 to 8.51, respectively). CONCLUSIONS: We found that the agreement between objective and subjective measures of frailty and physical function was poor. Objective measures of frailty and physical function were associated with mortality, and subjective measures of frailty were associated with dialysis modality choice.
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Actitud del Personal de Salud , Actitud Frente a la Salud , Toma de Decisiones Clínicas , Fragilidad/complicaciones , Diálisis Renal , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia , Anciano , Anciano de 80 o más Años , Femenino , Fragilidad/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Insuficiencia Renal Crónica/diagnóstico , Índice de Severidad de la EnfermedadRESUMEN
RATIONALE & OBJECTIVE: Most patients with kidney failure receive hemodialysis 3 times per week in a facility. More frequent and longer duration dialysis prescriptions improve a number of key outcome measures. These prescriptions are best suited to self-care and home regimens. The Quanta SC+ hemodialysis system is a novel device with demonstrated ease of use for patients and health care practitioners through human factors testing. The primary objective of this study is to report the efficacy and safety of the SC+ system using conventional hemodialysis prescriptions. STUDY DESIGN: Nonrandomized observational study. SETTING & PARTICIPANTS: Prevalent hemodialysis patients in 4 sites in the United Kingdom were recruited to switch from their current device to the SC+ system with no other changes to their prescription. INTERVENTIONS: SC+ hemodialysis system. OUTCOMES: Efficacy data were collected in terms of dialysis adequacy, urea reduction ratios, and net fluid removal accuracy. RESULTS: 60 patients were enrolled in the study, resulting in 1,333 evaluable treatments. The threshold single-pool Kt/V of 1.2 was exceeded in 96.6% of treatments in patients receiving 3-times-weekly regimens, whereas the threshold standard Kt/V of 2.1 was exceeded in 94% of treatments and 97.6% of treatments in patients without significant residual kidney function. Ultrafiltration accuracy was determined by measuring net fluid removal and validated to be within acceptable limits. The adverse event profile during treatment was typical of hemodialysis. There were no serious adverse events. LIMITATIONS: Few patients on high-frequency treatment regimens were enrolled. CONCLUSIONS: The SC+ system delivers safe and effective hemodialysis across a range of patients and dialysis prescriptions. It is one of the smallest systems available and has validated usability for patients to perform self-care safely with minimal training. This device may encourage patients to feel empowered to take on home hemodialysis, unlocking beneficial clinical and patient-reported outcomes associated with these modalities.
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Canadian indigenous (First Nations) have rates of kidney failure that are 2- to 4-fold higher than the non-indigenous general Canadian population. As such, a strategy of targeted screening and treatment for CKD may be cost-effective in this population. Our objective was to assess the cost utility of screening and subsequent treatment for CKD in rural Canadian indigenous adults by both estimated glomerular filtration rate and the urine albumin-to-creatinine ratio. A decision analytic Markov model was constructed comparing the screening and treatment strategy to usual care. Primary outcomes were presented as incremental cost-effectiveness ratios (ICERs) presented as a cost per quality-adjusted life-year (QALY). Screening for CKD was associated with an ICER of $23,700/QALY in comparison to usual care. Restricting the model to screening in communities accessed only by air travel (CKD prevalence 34.4%), this ratio fell to $7,790/QALY. In road accessible communities (CKD prevalence 17.6%) the ICER was $52,480/QALY. The model was robust to changes in influential variables when tested in univariate sensitivity analyses. Probabilistic sensitivity analysis found 72% of simulations to be cost-effective at a $50,000/QALY threshold and 93% of simulations to be cost-effective at a $100,000/QALY threshold. Thus, targeted screening and treatment for CKD using point-of-care testing equipment in rural Canadian indigenous populations is cost-effective, particularly in remote air access-only communities with the highest risk of CKD and kidney failure. Evaluation of targeted screening initiatives with cluster randomized controlled trials and integration of screening into routine clinical visits in communities with the highest risk is recommended.
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Costos de la Atención en Salud , Servicios de Salud del Indígena/economía , Indígenas Norteamericanos , Tamizaje Masivo/economía , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/economía , Servicios de Salud Rural/economía , Adulto , Albuminuria/diagnóstico , Albuminuria/economía , Albuminuria/etnología , Aviación , Simulación por Computador , Análisis Costo-Beneficio , Técnicas de Apoyo para la Decisión , Diagnóstico Precoz , Femenino , Humanos , Masculino , Manitoba/epidemiología , Cadenas de Markov , Tamizaje Masivo/métodos , Persona de Mediana Edad , Modelos Económicos , Vehículos a Motor , Pruebas en el Punto de Atención/economía , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Años de Vida Ajustados por Calidad de Vida , Insuficiencia Renal Crónica/etnología , Insuficiencia Renal Crónica/terapia , Factores de TiempoRESUMEN
Hydrogen peroxide (H2O2) is involved in the regulation of numerous reproductive and morphogenic processes across an array of taxa. Extracellular H2O2 can be widespread in oceanic waters, and elevated sea surface temperatures can cause increased levels of intracellular H2O2 within cnidarian tissue, but it remains unclear how this compound affects early life-history processes in corals, such as fertilization, metamorphosis, and settlement. To evaluate the effects of H2O2 on multiple stages of recruitment, experiments were conducted using Caribbean corals with various reproductive modes, including the brooders Porites astreoides and Favia fragum and the broadcast-spawning species Acropora palmata and Orbicella franksi. H2O2 accelerated settlement in all brooding species tested. Concentrations of 1000 µmol l-1 H2O2 caused close to 100% settlement in all larval age classes, regardless of exposure duration. As larvae aged, the required threshold of H2O2 capable of inducing settlement decreased. In contrast, H2O2 concentrations of 100 µmol l-1 or greater caused a significant reduction in metamorphosis and settlement in the larvae of spawners. Furthermore, fertilization of their gametes was inhibited in the presence of H2O2 concentrations as low as 100 µmol l-1. In Porites astreoides larvae, internal levels of H2O2 reached a maximal value of 75 µmol l-1 following 48 h of incubation at 31 °C. This concentration was found to significantly alter settlement rates in both brooding coral species and likely induced a cellular cascade in the settlement signaling pathway. The results of this study suggest that temperature stress influences H2O2 production, which in turn impacts coral settlement. While it is unlikely that the current levels of externally derived concentrations of oceanic H2O2 are affecting coral larvae, internal concentrations (produced under heat stress) have the capacity to impact recruitment under a changing climate.
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Antozoos/efectos de los fármacos , Peróxido de Hidrógeno/toxicidad , Animales , Antozoos/fisiología , Fertilización/efectos de los fármacos , Especificidad de la Especie , TemperaturaRESUMEN
A definitive understanding of the link between heart and kidney disease remains elusive. Bittencourt et al. explore the association between chronic kidney disease (CKD) status, severity of coronary lesions, and clinical outcome in more than 1500 consecutive adult subjects who underwent a clinically indicated coronary computed tomography angiography for the evaluation of the coronary disease. We discuss the implications of their findings in the context of our current understanding of the development of heart disease in CKD.
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Enfermedad Coronaria/diagnóstico por imagen , Infarto del Miocardio/epidemiología , Insuficiencia Renal Crónica/fisiopatología , Femenino , Humanos , Masculino , RadiografíaRESUMEN
Successful larval settlement and recruitment by corals is critical for the survival of coral reef ecosystems. Several closely related strains of γ-proteobacteria have been identified as cues for coral larval settlement, but the inductive properties of other bacterial taxa naturally occurring in reef ecosystems have not yet been explored. In this study, we assayed bacterial strains representing taxonomic groups consistently detected in corals for their ability to influence larval settlement in the coral Porites astreoides. We identified one α-proteobacterial strain, Roseivivax sp. 46E8, which significantly increased larval settlement in P. astreoides. Logarithmic growth phase (log phase) cell cultures of Roseivivax sp. 46E8 and filtrates (0.22µm) from log phase Roseivivax sp. 46E8 cultures significantly increased settlement, suggesting that an extracellular settlement factor is produced during active growth phase. Filtrates from log phase cultures of two other bacterial isolates, Marinobacter sp. 46E3, and Cytophaga sp. 46B6, also significantly increased settlement, but the cell cultures themselves did not. Monospecific biofilms of the three strains did not result in significant increases in larval settlement. Organic and aqueous/methanol extracts of Roseivivax sp. 46E8 cultures did not affect larval settlement. Examination of filtrates from cell cultures showed that Roseivivax sp. 46E8 spontaneously generated virus-like particles in log and stationary phase growth. Though the mechanism of settlement enhancement by Roseivivax sp. 46E8 is not yet elucidated, our findings point to a new aspect of coral-Roseobacter interactions that should be further investigated, especially in naturally occurring, complex microbial biofilms on reef surfaces.
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Antozoos/microbiología , Antozoos/fisiología , Roseobacter/fisiología , Animales , Arrecifes de Coral , Larva/microbiología , Roseobacter/virologíaRESUMEN
Two new steroidal alkaloids, along with a previously reported one of the plakinamine class, were isolated from the sponge Corticium sp. collected from Guam. The structures of the new compounds were determined by combined spectroscopic methods. These compounds exhibited moderate cytotoxicity and antifungal activity as well as DNA- and RNA-cleaving activities.
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Alcaloides/aislamiento & purificación , Antiinfecciosos/aislamiento & purificación , Antifúngicos/aislamiento & purificación , Antineoplásicos/aislamiento & purificación , Poríferos/química , Esteroides/aislamiento & purificación , Alcaloides/química , Alcaloides/farmacología , Animales , Antibacterianos , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antifúngicos/química , Antifúngicos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Candida albicans/efectos de los fármacos , Cromatografía Líquida de Alta Presión , ADN/efectos de los fármacos , ADN Bacteriano/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Electroforesis , Escherichia coli/genética , Guam , Humanos , Leucemia , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , ARN Ribosómico 16S/efectos de los fármacos , Espectrofotometría Infrarroja , Espectrofotometría Ultravioleta , Esteroides/química , Esteroides/farmacología , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
The potent antitumor agent dolastatin 10 (1) was originally isolated from the sea hare Dolabella auricularia, and we now report its isolation from the marine cyanobacterium Symploca sp. VP642 from Palau. The chemically related analogue symplostatin 1 (2) has been reisolated from Guamanian and Hawaiian varieties of S. hydnoides and its total stereochemistry completed by determining the N,N-dimethylisoleucine unit to be L. Symplostatin 1 (2), like dolastatin 10 (1), is a potent microtubule inhibitor. The antitumor activity of 2 was assessed in vivo against several murine tumors. Symplostatin 1 (2) was effective against a drug-insensitive mammary tumor and a drug-insensitive colon tumor; however, it was only slightly effective against two MDR tumors.
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Antineoplásicos/aislamiento & purificación , Cianobacterias/química , Depsipéptidos , Oligopéptidos/aislamiento & purificación , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Aplysia/química , Cromatografía Líquida de Alta Presión , Neoplasias Colorrectales/metabolismo , Cianobacterias/aislamiento & purificación , Citotoxinas/química , Citotoxinas/aislamiento & purificación , Resistencia a Múltiples Medicamentos , Femenino , Fibroblastos/metabolismo , Técnica del Anticuerpo Fluorescente , Guam , Hawaii , Humanos , Espectroscopía de Resonancia Magnética , Neoplasias Mamarias Animales/metabolismo , Ratones , Estructura Molecular , Neoplasias/metabolismo , Oligopéptidos/química , Oligopéptidos/farmacología , Palau , Neoplasias Pancreáticas/metabolismo , Espectrometría de Masa Bombardeada por Átomos Veloces , Espectrofotometría Ultravioleta , Estereoisomerismo , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
Apratoxin A (1), a potent cytotoxin with a novel skeleton, has been isolated from the marine cyanobacterium Lyngbya majuscula Harvey ex Gomont. This cyclodepsipeptide of mixed peptide-polyketide biogenesis bears a thiazoline ring flanked by polyketide portions, one of which possesses an unusual methylation pattern. Its gross structure has been elucidated by spectral analysis, including various 2D NMR techniques. The absolute configurations of the amino acid-derived units were determined by chiral HPLC analysis of hydrolysis products. The relative stereochemistry of the new dihydroxylated fatty acid unit, 3,7-dihydroxy-2,5,8,8-tetramethylnonanoic acid, was elucidated by successful application of the J-based configuration analysis originally developed for acyclic organic compounds using carbon-proton spin-coupling constants ((2,3)J(C,H)) and proton-proton spin-coupling constants ((3)J(H,H)); its absolute stereochemistry was established by Mosher analysis. The conformation of 1 in solution was mimicked by molecular modeling, employing a combination of distance geometry and restrained molecular dynamics. Apratoxin A (1) possesses IC(50) values for in vitro cytotoxicity against human tumor cell lines ranging from 0.36 to 0.52 nM; however, it was only marginally active in vivo against a colon tumor and ineffective against a mammary tumor.
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Citotoxinas/química , Citotoxinas/farmacología , Depsipéptidos , Péptidos Cíclicos/química , Péptidos Cíclicos/farmacología , Adenocarcinoma/tratamiento farmacológico , Animales , Toxinas Bacterianas/química , Toxinas Bacterianas/aislamiento & purificación , Toxinas Bacterianas/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Cianobacterias/química , Citotoxinas/aislamiento & purificación , Femenino , Humanos , Concentración 50 Inhibidora , Masculino , Toxinas Marinas/química , Toxinas Marinas/aislamiento & purificación , Toxinas Marinas/farmacología , Ratones , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Péptidos Cíclicos/aislamiento & purificación , Células Tumorales CultivadasRESUMEN
Two new cyclodepsipeptides have been isolated from a population of the marine cyanobacterium Lyngbya majuscula collected at Piti Bomb Holes, Guam. They appear to be unique to this particular Guamanian collection and have been named pitipeptolides A (1) and B (2). Their structures have been elucidated by spectroscopic techniques and by characterization of degradation products. Distinctive features include the presence of a 2,2-dimethyl-3-hydroxy-7-octynoic acid residue in 1 and a 2,2-dimethyl-3-hydroxy-7-octenoic acid residue in 2, previously shown to be biosynthetic signatures of cyanobacterial metabolites. Pitipeptolides A (1) and B (2) exhibit weak cytotoxicity against LoVo cancer cells, but possess moderate antimycobacterial activity and stimulate elastase activity.
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Cianobacterias/química , Depsipéptidos , Péptidos Cíclicos/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Estructura Molecular , Péptidos Cíclicos/químicaRESUMEN
Sacoglossans are a group of opisthobranch mollusks that have been the source of numerous secondary metabolites; however, there are few examples where a defensive ecological role for these compounds has been demonstrated experimentally. We investigated the deterrent properties of the sacoglossan Elysia rufescens and its food alga Bryopsis sp. against natural fish predators. Bryopsis sp. produces kahalalide F, a major depsipeptide that is accumulated by the sacoglossan and that shows in vitro cytotoxicity against several cancer cell lines. Our data show that both Bryopsis sp. and Elysia rufescens are chemically protected against fish predators, as indicated by the deterrent properties of their extracts at naturally occurring concentrations. Following bioassay-guided fractionation, we observed that the antipredatory compounds of Bryopsis sp. were present in the butanol and chloroform fractions, both containing the depsipeptide kahalalide F. Antipredatory compounds of Elysia rufescens were exclusively present in the dichloromethane fraction. Further bioassay-guided fractionation led to the isolation of kahalalide F as the only compound responsible for the deterrent properties of the sacoglossan. Our data show that kahalalide F protects both Brvopsis sp. and Elysia rufescens from fish predation. This is the first report of a diet-derived depsipeptide used as a chemical defense in a sacoglossan.
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Antineoplásicos/farmacología , Chlorophyta/química , Depsipéptidos , Peces , Moluscos/química , Péptidos/farmacología , Conducta Predatoria , Adaptación Fisiológica , Animales , Antineoplásicos/aislamiento & purificación , Bioensayo , Cadena Alimentaria , Péptidos/aislamiento & purificaciónRESUMEN
A new indanone (1) has been isolated from the filamentous marine cyanobacterium Lyngbya majuscula, and its structure determined spectroscopically. Vascular endothelial growth factor (VEGF) is an important regulator of tumor angiogenesis. Compound 1 inhibits hypoxia-induced activation of the VEGF gene promoter in Hep3B human liver tumor cells, in vitro.
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Cianobacterias/química , Regulación de la Expresión Génica/efectos de los fármacos , Indanos/química , Hipoxia de la Célula , Factores de Crecimiento Endotelial/genética , Humanos , Indanos/aislamiento & purificación , Indanos/farmacología , Linfocinas/genética , Regiones Promotoras Genéticas , Células Tumorales Cultivadas , Factor A de Crecimiento Endotelial Vascular , Factores de Crecimiento Endotelial VascularRESUMEN
An analogue of the potent microfilament-disrupter lyngbyabellin A (1) has been isolated as a minor metabolite from the marine cyanobacterium Lyngbya majuscula collected at Apra Harbor, Guam. It possesses slightly weaker cytotoxicity than 1 and has been named lyngbyabellin B (2). Primarily NMR spectroscopy was used to determine its structure. The absolute configuration of 2 has been ascertained by chiral HPLC analysis of degradation products and by comparison with lyngbyabellin A (1). The known modified tetrapeptide lyngbyapeptin A (3) has also been found in the same extract, and its absolute stereochemistry could be determined for the first time.
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Toxinas Bacterianas/aislamiento & purificación , Cianobacterias/química , Citotoxinas/aislamiento & purificación , Depsipéptidos , Toxinas de Lyngbya/aislamiento & purificación , Tiazoles/aislamiento & purificación , Toxinas Bacterianas/química , Toxinas Bacterianas/farmacología , Citotoxinas/química , Citotoxinas/farmacología , Concentración 50 Inhibidora , Toxinas de Lyngbya/química , Toxinas de Lyngbya/farmacología , Espectroscopía de Resonancia Magnética , Estructura Molecular , Péptidos Cíclicos/química , Péptidos Cíclicos/aislamiento & purificación , Péptidos Cíclicos/farmacología , Tiazoles/química , Tiazoles/farmacologíaRESUMEN
Six new metabolites have been isolated from a lyngbyastatin 2-producing strain of the marine cyanobacterium Lyngbya majuscula collected at Apra Harbor, Guam, and their structures elucidated. These linear lipopeptides have been assigned the trivial names apramides A-F (1-6). From a more recent collection of this cyanobacterium, a structurally related compound, apramide G (7), has been found instead of apramides A-F (1-6). Structure elucidation of the lipopeptides 1-7 is based on spectroscopic techniques and chiral chromatography of hydrolysis products. The apramides appear as NMR-spectroscopically distinguishable conformers in solution, and this has been ascribed to the presence of a thiazole-containing modified amino acid unit.
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Cianobacterias/química , Lipoproteínas/aislamiento & purificación , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Guam , Lipoproteínas/química , Espectroscopía de Resonancia Magnética , Rotación Óptica , Espectrometría de Masa Bombardeada por Átomos Veloces , Espectrofotometría Infrarroja , Espectrofotometría UltravioletaRESUMEN
Four new triterpenoid saponins were isolated, along with two known 30-norlanostane-type saponins- sarasinosides A(1) (1) and A(3) (2)-from the sponge Melophlus isis collected from Guam. The structures of these new compounds (3-6) proved to be 30-norlanosta-8(14),24-dien-23-ones bearing two hydroxyl groups or the corresponding methoxy groups at the 9alpha,15alpha- and 9alpha, 15beta-positions and the pentasaccharide portion identical with those of 1 and 2 at the 3beta position, by spectral, chemical, and GC analyses.
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Poríferos/química , Saponinas/aislamiento & purificación , Triterpenos/aislamiento & purificación , Animales , Conformación de Carbohidratos , Secuencia de Carbohidratos , Datos de Secuencia Molecular , Saponinas/química , Análisis Espectral , Triterpenos/químicaRESUMEN
Lyngbyabellin A (1), a significantly cytotoxic compound with unusual structural features, was isolated from a Guamanian strain of the marine cyanobacterium Lyngbya majuscula. This novel peptolide is structurally related to dolabellin (2) in that both depsipeptides bear a dichlorinated beta-hydroxy acid and two functionalized thiazole carboxylic acid units. Its gross structure has been elucidated by spectral analysis, including 2D NMR techniques. The absolute stereochemistry of 1 was determined by chiral HPLC analysis of hydrolysis products and by characterization of the degradation products methyl 7,7-dichloro-3-hydroxy-2,2-dimethyloctanoate (3) and the corresponding acid 4. The total structure was further supported by molecular modeling studies. The isolation of 1 from L. majuscula once more supports the proposal that many compounds originally isolated from the sea hare Dolabella auricularia are of cyanobacterial origin. Lyngbyabellin A (1) was shown to be a potent disrupter of the cellular microfilament network.
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Antineoplásicos/aislamiento & purificación , Cianobacterias/química , Depsipéptidos , Péptidos Cíclicos/aislamiento & purificación , Antineoplásicos/química , Antineoplásicos/farmacología , Cromatografía Líquida de Alta Presión , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Células KB , Espectroscopía de Resonancia Magnética , Músculo Esquelético/química , Músculo Esquelético/efectos de los fármacos , Péptidos Cíclicos/química , Péptidos Cíclicos/farmacología , Espectrometría de Masa Bombardeada por Átomos Veloces , Espectrofotometría Infrarroja , Estereoisomerismo , Células Tumorales CultivadasRESUMEN
The structure of apakaochtodene A, the minor isomer of two tetrahalogenated ochtodene monoterpenes, isolated from the red marine alga Portieria hornemannii (Lyngbye) Silva has been identified as 6(S)-bromo-1,4(S),8(R)-trichloro-2(Z)-ochtodene (1) by NMR spectral and X-ray crystallographic analysis. Its geometrical isomer, apakaochtodene B (2), which could not be separated from 1 and thus characterized as a 95:5 mixture of 2:1 had (1)H and (13)C NMR spectral characteristics similar to previously known ochtodene (3) and the related tetrahalogenated monoterpene 4.
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Monoterpenos , Rhodophyta/química , Terpenos/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Espectroscopía de Resonancia Magnética , Biología Marina , Estructura Molecular , Terpenos/químicaRESUMEN
An analogue of dolastatin 13 (2) has been isolated from a marine cyanobacterium, Symploca hydnoides, collected near Guam. This new cyclic depsipeptide contains a L-methionine sulfoxide residue; however, the sulfoxide exists as both R- and S-forms, resulting in the doubling of several signals in the 1H and 13C NMR spectra. Structure elucidation required extensive application of 2-D NMR techniques such as COSY, HMQC, HMBC, and ROESY. The trivial name symplostatin 2 (1) has been assigned to the new metabolite and its isolation from S. hydnoides further supports the proposal that many compounds originally isolated from the sea hare Dolabella auricularia are most probably of cyanobacterial origin.