RESUMO
One of the primary current astrobiological goals is to understand the limits of microbial resistance to extraterrestrial conditions. Much attention is paid to ionizing radiation, since it can prevent the preservation and spread of life outside the Earth. The aim of this research was to study the impact of accelerated He ions (150 MeV/n, up to 1 kGy) as a component of the galactic cosmic rays on the black fungus C. antarcticus when mixed with Antarctic sandstones-the substratum of its natural habitat-and two Martian regolith simulants, which mimics two different evolutionary stages of Mars. The high dose of 1 kGy was used to assess the effect of dose accumulation in dormant cells within minerals, under long-term irradiation estimated on a geological time scale. The data obtained suggests that viable Earth-like microorganisms can be preserved in the dormant state in the near-surface scenario for approximately 322,000 and 110,000 Earth years within Martian regolith that mimic early and present Mars environmental conditions, respectively. In addition, the results of the study indicate the possibility of maintaining traces within regolith, as demonstrated by the identification of melanin pigments through UltraViolet-visible (UV-vis) spectrophotometric approach.
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BACKGROUND AND OBJECTIVES: Lanthanum carbonate (LC) is a nonaluminum, noncalcium phosphate binder that is effective for hyperphosphatemia in dialysis patients. However, its efficacy and cost-effectiveness as second-line therapy have not been fully examined. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We first conducted a multicenter, open-label, 16-week clinical trial to examine the effect of additive LC in 116 hemodialysis patients who had uncontrolled hyperphosphatemia with conventional phosphorus-lowering therapy alone. Based on these clinical data, a state transition model was developed to evaluate the benefits and costs associated with LC as second-line therapy. Reduced risks for cardiovascular morbidity and mortality among patients treated with LC arise through more of the population achieving the target phosphorus levels. Uncertainty was explored through sensitivity analysis. RESULTS: After 16 weeks of additive LC treatment, mean serum phosphorus levels decreased from 7.30 ± 0.90 to 5.71 ± 1.32 mg/dl, without significant changes in serum calcium or intact parathyroid hormone levels. A subsequent cost-effectiveness analysis showed that compared with conventional treatment, additive LC incurred an average additional lifetime cost of $22,054 per person and conferred an additional 0.632 quality-adjusted life years (QALYs). This resulted in an incremental cost-effectiveness ratio of $34,896 per QALY gained. Applying a cost-effectiveness threshold of $50,000 per QALY, a probabilistic sensitivity analysis showed that additive LC had a 97.4% probability of being cost-effective compared with conventional treatment. CONCLUSIONS: Our results indicate that the use of LC as second-line therapy would be cost-effective among hemodialysis patients with uncontrolled hyperphosphatemia in Japan.
Assuntos
Quelantes/economia , Quelantes/uso terapêutico , Custos de Medicamentos , Hiperfosfatemia/tratamento farmacológico , Falência Renal Crônica/terapia , Lantânio/economia , Lantânio/uso terapêutico , Fósforo/sangue , Diálise Renal , Adolescente , Adulto , Idoso , Análise de Variância , Biomarcadores/sangue , Doenças Cardiovasculares/economia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Análise Custo-Benefício , Feminino , Humanos , Hiperfosfatemia/sangue , Hiperfosfatemia/economia , Hiperfosfatemia/etiologia , Japão , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/economia , Masculino , Pessoa de Meia-Idade , Modelos Econômicos , Anos de Vida Ajustados por Qualidade de Vida , Diálise Renal/efeitos adversos , Diálise Renal/economia , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
Hyponatremia is the most common electrolyte disorder in hospitalized patients and is associated with the risk of intractable seizures and death. The effectiveness of conventional therapies for hyponatremia is inconsistent, and the rapid correction of plasma sodium levels is thought to result in the occurrence of neurological complications. Arginine vasopressin (AVP) is the primary regulator of renal electrolyte-free water reabsorption via AVP-receptor type 2 (V2-R), and inappropriate or excessive AVP secretion independent of serum osmolality frequently causes excessive water retention, which is the etiological basis of hyponatremia. Therefore, the use of V2-R antagonists as anti-hyponatremic drugs in the clinical setting is anticipated to be reliable and safe. Conivaptan hydrochloride (YM087) is a novel dual AVP-R antagonist for AVP-R types 1a (V1a) and V2-R. In vitro studies have shown that it possesses high affinity for V1a-R and V2-R without any species differences. It also potently inhibited AVP-induced intracellular signaling through human V2 and V1a receptors with no agonistic activity. Conivaptan hydrochloride improved the plasma sodium concentration and plasma osmolality in hyponatremic rats, and its effectiveness was demonstrated in hyponatremic patients. This drug has been approved for use in the United States, which will bring relief to patients with hyponatremia.
Assuntos
Antagonistas dos Receptores de Hormônios Antidiuréticos , Benzazepinas/farmacologia , Hiponatremia/tratamento farmacológico , Animais , Benzazepinas/uso terapêutico , Ensaios Clínicos Fase III como Assunto , Avaliação Pré-Clínica de Medicamentos/métodos , Humanos , Hiponatremia/fisiopatologia , Projetos de PesquisaRESUMO
AIM: To study the effects of decreased dialysis calcium on mineral metabolism. METHODS: Dialysis calcium concentration was switched from 3.0 mEq/L to 2.5 mEq/L. Changes of serum Ca, P, and PTH were monitored for 6 months in 58 hemodialysis patients. RESULTS: Serum calcium decreased 2 weeks after the switch of dialysate, although it returned to the basal level after 6 months because of increased dosage of vitamin D. Phosphorus transiently increased after the switch. I-PTH increased in patients whose i-PTH before the switch was less than 100 pg/mL. PTH decreased in patients whose i-PTH exceeded 300 pg/mL. CONCLUSION: Decreased dialysis calcium produced lower serum calcium and better PTH control.