Evaluating the safety profile of focused ultrasound and microbubble-mediated treatments to increase blood-brain barrier permeability

Introduction: Treatment of several diseases of the brain are complicated by the presence of the skull and the blood-brain barrier (BBB). Focused ultrasound (FUS) and microbubble (MB)-mediated BBB treatment is a minimally invasive method to transiently increase the permeability of blood vessels in targeted brain areas. It can be used as a general delivery system to increase the concentration of therapeutic agents in the brain parenchyma.

Areas covered: Over the past two decades, the safety of using FUS+MBs to deliver agents across the BBB has been interrogated through various methods of imaging, histology, biochemical assays, and behavior analyses. Here we provide an overview of the factors that affect the safety profile of these treatments, describe methods by which FUS+MB treatments are controlled, and discuss data that have informed the assessment of treatment risks.

Expert opinion: There remains a need to assess the risks associated with clinically relevant treatment strategies, specifically repeated FUS+MB treatments, with and without therapeutic agent delivery. Additionally, efforts to develop metrics by which FUS+MB treatments can be easily compared across studies would facilitate a more rapid consensus on the risks associated with this intervention.     

Carbohydrate Electrolyte Solutions Enhance Endurance Capacity in Active Females

The purpose of the present study was to investigate the effects of supplementation with a carbohydrate-electrolyte solution (CES) in active females during a prolonged session of submaximal running to exhaustion. Eight healthy active females volunteered to perform a session of open-ended running to exhaustion at 70% of their maximal oxygen consumption on a treadmill during the follicular phase of their menstrual cycle on two occasions. During each run, the subjects consumed either 3mL·kg⁻¹ body mass of a 6% CES or a placebo drink (PL) every 20 min during exercise. The trials were administered in a randomized double-blind, cross-over design. During the run, the subjects ingested similar volumes of fluid in two trials (CES: 644 ± 75 mL vs. PL: 593 ± 66 mL, p > 0.05). The time to exhaustion was 16% longer during the CES trial (106.2 ± 9.4 min) than during the PL trial (91.6 ± 5.9 min) (p < 0.05). At 45 min during exercise, the plasma glucose concentration in the CES trial was higher than that in PL trial. No differences were observed in the plasma lactate level, respiratory exchange ratio, heart rate, perceived rate of exertion, sensation of thirst, or abdominal discomfort between the two trials (p > 0.05). The results of the present study confirm that CES supplementation improves the moderate intensity endurance capacity of active females during the follicular phases of the menstrual cycle. However, the exogenous oxidation of carbohydrate does not seem to explain the improved capacity after CES supplementation.     

First Report of Laribacter hongkongensis Peritonitis in Continuous Ambulatory Peritoneal Dialysis

The most common pathogens associated with peritonitis in patients on continuous ambulatory peritoneal dialysis (CAPD) are gram-positive bacteria, which constitute 60 – 80% of all isolates. With the advancement of molecular technologies for bacterial identification, cases of CAPD-related peritonitis caused by bacteria previously not known to be associated with this clinical condition have been reported. Here we report the first case of CAPD-related peritonitis due to Laribacter hongkongensis.     

Little girl who conquered the "ALPPS’’

An insufficient future liver remnant(FLR)is associated with post-hepatectomy liver failure.Associating liver partition and portal vein ligation for stage hepatectomy(ALPPS)has been shown to be effective for the induction of rapid FLR hypertrophy so as to improve the resectability in patients with insufficient FLR.We hereby report our experience of this novel approach for a 6-year-old patient with hepatoblastoma.Computed tomography showed a hepatoblastoma measuring12.5 cm×9.9 cm×11.7 cm in the right liver(Couinaud segmentⅣ,ⅤandⅧ).Volumetric assessment of the FLR i.e.,left lateral section was 112.6 mL i.e.,21.2%of the estimated total liver volume.In view of the small-for-size FLR,ALPPS was contemplated.An anterior approach was adopted for the in-situ parenchymal split without mobilisation of the right liver.FLR volumetry on the seventh postoperative day was 160.7 mL,which represented a 46.1%gain in volume,and a FLR/ESLV ratio of 30.2%.A right trisectionectomy was performed on the eighth postoperative day.Postoperative recovery was uneventful.Patient was discharged on day 16 after the first operation.To our knowledge,this was the first report that showed the applicability of ALPPS to a paediatric patient.     

Heterogeneous phenotypes of platelet and plasma von Willebrand factor in obligatory heterozygotes for severe von Willebrand disease

To characterize the heterogeneity of severe (type III) von Willebrand disease (vWD), plasma and platelet von Willebrand factor antigen (vWF:Ag) and ristocetin cofactor activity (Ricof) were measured in 28 obligatory heterozygotes (ie, parents or children of probands from 15 different kindreds with severe vWD). On the average, heterozygotes had low levels of vWF in both platelets and plasma. There was, however, considerable heterogeneity, with four distinct patterns. Eleven heterozygotes had concordant reduction of vWF:Ag and Ricof in both plasma and platelets; five had low levels of vWF:Ag and Ricof in plasma contrasting with normal levels in platelets; eight had a peculiar pattern, the reverse of the above (ie, low levels in platelets and normal levels in plasma); and in one, both vWF measurements were normal in plasma and platelets. These patterns were genetically determined: they were consistent in four couples of consanguineous heterozygotes and in two couples carrying the same gene deletion. Only the remaining three heterozygotes had no clearly identifiable pattern. Other findings of this study were that although most of the heterozygotes had normal bleeding times, the 7 of 28 who had prolonged bleeding times had concordantly low levels of vWF measurements in both plasma and platelets. In conclusion, this large series of obligatory heterozygotes provides evidence for phenotypic and genotypic heterogeneity of severe vWD.     

Carrier detection in hemophilia A: a cooperative international study. I. The carrier phenotype

Eight laboratories in six countries cooperated to clarify several issues concerning the phenotypes of heterozygous carriers of hemophilia "A." Plasma levels of factor VIII (F.VIII:C, formerly VIII:C) and von Willebrand factor (VWF:Ag, formerly VIIIR:Ag) of carriers and normal women were determined by various "in-house" methods; a single lyophilized plasma standard was used for all assays. Analysis of the collated data from 336 carriers (296 obligatory carriers and 40 sporadic carriers) and 137 normal women showed that there was no difference in the F.VIII:C levels of "paternal" carriers (women who had obtained the abnormal gene from their fathers) and "maternal" carriers. Neither was there a difference in the VWF:Ag levels of normal women and either type of carrier. Age was found to have a significant effect on both F.VIII:C and VWF:Ag, values being higher at very young and very old ages, the minima occurring in the 25- to 30-year range. ABO blood type had a striking effect. Women of types A, B, and AB (designated non- O in the study), both normals and carriers, had significantly higher levels of both factors than did women of type O. Analysis by laboratories showed that differences in mean levels of both factors between laboratories were highly significant. It was concluded that age, ABO blood type, and laboratory variation should be taken into account in carrier detection.