Purging of acute myeloid leukemic cells by ether lipids and hyperthermia

Ether lipids (EL) and hyperthermia have been shown to possess a relatively selective cytotoxicity to leukemic cells. In this study, the combined effects of EL (ET-18-OCH3, ET-16-NHCOCH3, or BM 41.440) and hyperthermia on the growth of hematopoietic progenitors, myeloid leukemic cell lines, and leukemic cells obtained from patients with acute myeloid leukemia (AML) were examined to determine if this combination resulted in a greater selective killing of leukemic cells than that achieved by either EL or heat alone. When the cells were treated simultaneously with EL (50 micrograms/mL) and hyperthermia (42 degrees C) for one hour, the killing of leukemic cell line cells was enhanced considerably. Among the three EL, however, the combination of ET-18-OCH3 and heat seemed to be the most cytotoxic to leukemic cell line cells with no effect on the growth of hematopoietic progenitors. An increase in the duration of treatment with ET-18-OCH3 to four hours with heat added during the last hour resulted in a further reduction of leukemic cell line cells while sparing 50% of hematopoietic progenitors after cryopreservation. The combined treatment with ET-18-OCH3 and heat also inhibited the growth of leukemic progenitors obtained from AML patients by 97% to 100%. These data indicate that the combined treatment with EL and hyperthermia might offer an efficient means to eliminate myeloid leukemic cells in vitro.     

Longitudinal association between ideal cardiovascular health status and muscular fitness in adolescents: The LabMed Physical Activity Study

Background and aims

Muscular fitness is an emerging predictor for cardiovascular disease mortality. The ideal cardiovascular health metrics has been inversely related to a subsequent cardiometabolic health in adulthood. However, evidence regarding muscular fitness and ideal cardiovascular health in adolescents is scarce. This study aimed to examine the longitudinal association between ideal cardiovascular health index and muscular fitness.

Different patterns of renal osteodystrophy in Iberoamerica

The various forms of renal osteodystrophy are predominant hyperparathyroid bone disease, mixed uremic osteodystrophy, low turnover osteomalacia, and adynamic bone disease. The present study analyses a total number of 1,209 bone biopsies from 5 different countries (Brazil, Uruguay, Argentina, Portugal, and Spain). Low turnover osteomalacia and mixed uremic osteodystrophy were more common in Brazil, Uruguay, and Argentina than in Portugal and Spain whereas predominant hyperparathyroid bone disease was seen more often in Portugal and Spain. In all centers, independent of the aluminum staining technique used, the extent of aluminum deposited in bone was greater in patients presenting with low bone turnover, whether from low turnover osteomalacia or adynamic bone disease, than in the predominant hyperparathyroid bone disease. In summary, even though recent reports have indicated that, over the last decade, the incidence of aluminum-induced toxicity was reduced, aluminum still seems to be implicated in a great percentage of symptomatic low bone remodelling lesions in Iberoamerica.     

Role of Rab27 in synaptic transmission at the squid giant synapse

Small GTPase Rab is a member of a large family of Ras-related proteins, highly conserved in eukaryotic cells, and thought to regulate specific type(s) and/or specific step(s) in intracellular membrane trafficking. Given our interest in synaptic transmission, we addressed the possibility that Rab27 (a close isoform of Rab3) could be involved in cytosolic synaptic vesicle mobilization. Indeed, preterminal injection of a specific antibody against squid Rab27 (anti-sqRab27 antibody) combined with confocal microscopy demonstrated that Rab27 is present on squid synaptic vesicles. Electrophysiological study of injected synapses showed that the anti-sqRab27 antibody inhibited synaptic release in a stimulation-dependent manner without affecting presynaptic action potentials or inward Ca²⁺ current. This result was confirmed in in vitro synaptosomes by using total internal reflection fluorescence microscopy. Thus, synaptosomal Ca²⁺-stimulated release of FM1-43 dye was greatly impaired by intraterminal anti-sqRab27 antibody. Ultrastructural analysis of the injected giant preterminal further showed a reduced number of docked synaptic vesicles and an increase in nondocked vesicular profiles distant from the active zone. These results, taken together, indicate that Rab27 is primarily involved in the maturation of recycled vesicles and/or their transport to the presynaptic active zone in the squid giant synapse.     

Prevalence of obstructive sleep apnea in patients with mucopolysaccharidosis types I,II, and VI in a reference center

Purpose

Mucopolysaccharidosis (MPS) encompasses a group of rare lysosomal storage disorders that are associated with the accumulation of glycosaminoglycans in organs and tissues. Respiratory disorders occur in all MPS types. In these patients, the prevalence of obstructive sleep apnea syndrome (OSAS), which may confer additional morbidity, remains overlooked, and the results of the few existing studies are controversial. The present study aimed to characterize the prevalence of OSAS in patients with MPS types I, II, and VI in a reference center.

Methods

Forty-five patients with MPS (I, n?=?17; II, n?=?16; and VI; n?=?12) in the Centro de Referência em Erros Inatos do Metabolismo, who underwent full-night polysomnography, were enrolled in a retrospective study. Demographic data and clinical history were collected from medical records of the first medical consultation.

Results

The prevalence of OSAS in patients with MPS was 69.8 %. MPS type I patients seemed to be more susceptible to OSA-induced hypoxemia, as indicated by reduced mean SpO₂ levels during both NREM and rapid eye movement sleep as well as during SpO₂ nadir.

Conclusions

Patients with MPS displayed a high prevalence of OSAS, often with moderate to high severity. Together, our results reinforce the need for OSAS screening in all patients with MPS.     

Diagnosis and management of hepatic artery in-stent restenosis after liver transplantation by optical coherence tomography:A case report

BACKGROUND Percutaneous transluminal angioplasty and stenting represent an effective treatment for hepatic artery stenosis after liver transplantation. In the first year after stenting, approximately 22% of patients experience in-stent restenosis, increasing the risk of artery thrombosis and related complications, and 50% experience liver failure. Although angiography is an important tool for diagnosis and the planning of therapeutic interventions, it may raise doubts, especially in small-diameter arteries, and it provides low resolution rates compared with newer intravascular imaging methods, such as optical coherence tomography(OCT).CASE SUMMARY A 64-year-old male developed hepatic artery stenosis one year after orthotropic liver transplantation and was successfully treated with percutaneous transluminal angioplasty with stenting. Five months later, the Doppler ultrasound results indicated restenosis. Visceral arteriography confirmed hepatic artery tortuosity but was doubtful for significant in-stent restenosis(ISR) and intrahepatic flow reduction. To confirm ISR, identify the etiology and guide treatment, OCT was performed. OCT showed severe stenosis due to four mechanisms: Focal and partial stent fracture, late stent malapposition, in-stent neointimal hyperplasia, and neoatherosclerosis.CONCLUSION Intravascular diagnostic methods can be useful in evaluating cases in which initial angiography results are not sufficient to provide a proper diagnosis of significant stenosis, especially with regard to ISR. A wide range of diagnoses are provided by OCT, resulting in different treatment options. Interventional radiologists should consider intravascular diagnostic methods as additional tools for evaluating patients when visceral angiography results are unclear.     

The morphological and molecular characterization of Henneguya rotunda n. sp., a parasite of the gill arch and fins of Salminus brasiliensis from the Mogi Guaçu River,Brazil

A new species of myxosporea (Henneguya rotunda n. sp.) was found in the membrane of the gill arch and the fins of Salminus brasiliensis in the Mogi Guaçu River, municipality of Pirassununga, São Paulo state, Brazil. Morphological and morphometric analyses using light microscopy revealed parasites with similar characteristics at both infection sites. The mature spores found infecting the fins had oval spore body with 7.1?±?0.2 μm in length, 5.6?±?0.2 μm in width, 3.7?±?0.1 μm in thickness, 16.4?±?1.2 μm in length of the caudal process, and 23.6?±?1.1 μm in total length of the spore. In a frontal view, the polar capsule was observed to be symmetrical with 3.4?±?0.2 μm in length and 1.8?±?0.1 μm in width. Mature spores contain six to seven turns of the polar filaments. The morphometric data concerning the spores obtained from plasmodia from the membrane of the gill arch were similar to those from the fins. Ultrastructure analysis revealed that the plasmodial wall was formed by a single membrane and had numerous pinocytotic canals connecting the outside of the plasmodia to the ectoplasm zone. Beyond that, various electron-translucent vesicles also were observed at the periphery of the plasmodium. The molecular analyses of the 18S rDNA gene from the spores obtained from the gill arch membrane and fin membrane showed that these sequences shared 100 % similarity. Phylogenetic studies using maximum parsimony and maximum likelihood methods demonstrated the polyphyletic clustering of the myxosporean parasites of characiform fishes. H. rotunda n. sp. clustered as a sister species of Myxobolus pantanalis, also a parasite of S. brasiliensis.