Ultrasound, microbubbles and the blood-brain barrier

The blood–brain barrier (BBB) is a specialized system of capillary endothelial cells that protects the brain from harmful substances in the blood stream, while supplying the brain with the required nutrients for proper function. The BBB controls transport through both tight junctions and metabolic barriers and is often a rate-limiting factor in determining permeation of therapeutic drugs into the brain. It is a significant obstacle for delivery of both small molecules and macromolecular agents. Although many drugs could be potentially used to treat brain disease, there has been no method that allows non-invasive-targeted delivery through the BBB. Recently, promising studies indicate that ultrasound can be used to locally deliver a drug or gene to a specific region of interest in the brain. If microbubbles are combined with ultrasound exposure, the effects of ultrasound can be focused upon the vasculature to reduce the acoustic intensity needed to produce BBB opening. Several avenues of transcapillary passage after ultrasound sonication have been identified including transcytosis, passage through endothelial cell cytoplasmic openings, opening of tight junctions and free passage through injured endothelium. This article reviews the topic of transient disruption of the BBB with ultrasound and microbubbles and addresses related safety issues. It also discusses possible roles of the BBB in brain disease and potential interactions with ultrasound and microbubbles in such disease states.     

Rapporteur report: Basics and technology and metrology and standards

The first and second sessions of the Workshop focussed on the basics of ultrasound and infrasound, their applications in both industry and medicine, and metrology and protection standards for ultrasound applications.     

Rapporteur report: Mechanisms and interactions

The first two talks of this session described the basic characteristics of the interaction of ultrasound with matter, the first (by V.F. Humphrey) concentrating on the physical interactions, with the second (by W.D. O’Brien, Jr.) focusing on the biophysical effects and mechanisms. The regimes covered by the first and second talks were of primarily high-frequency (O(MHz)) ultrasound in liquids and tissue, respectively. In contrast, the third and final talk of the session (by M. Alves-Pereira) discussed observations made by her group of the vibroacoustic effects of low-frequency noise and infrasound, propagating through air, on humans and animals.     

Effects of shear stress on endothelial cells: possible relevance for ultrasound applications

This review forms part of a series of papers resulting from a workshop on safety of ultrasound applications. The physical effects of ultrasound include generation of steady streaming in large fluid volumes, and micro-streaming around contrast bubbles. Such streaming induces shear stress acting on the vascular endothelium. This review provides a discussion on the levels of endothelial shear stress associated with diagnostic ultrasound applications, and on the biological effects of shear stress acting on the endothelial cells. Depending on vessel size and ultrasound characteristics, shear stresses associated with streaming and micro-streaming may exceed the physiological levels associated with the flow of blood by many orders of magnitude. The resulting biological effects could range anywhere from activation of normal shear stress sensors such as ion channels, damage of the endothelial surface layer, reversible perforation of the membrane, to cell detachment and lysis. The possible presence of such biological effects does not necessarily mean that the effects are harmful for the individual. However, considering the ever-increasing use of ultrasound, a further investigation into these shear stress-related effects, using both experiments and modelling, is desired. Apart from safety concerns, such effects may provide a base for strategies aimed at targeted delivery of drugs.     

Ultrasound and matter--physical interactions

The basic physical characteristics of ultrasound waves are reviewed in terms of the typical displacements, velocities, accelerations and pressures generated in various fluid media as a function of frequency. The effects on wave propagation of interfaces are considered, and the way in which waves are reflected, transmitted and mode converted at interfaces introduced. Then the nonlinear propagation of high amplitude ultrasound is explained, and its consequences, including the generation of harmonic frequencies and enhanced attenuation, considered. The absorption of ultrasonic waves and the resulting heat deposition in absorbing media are described together with factors determining the resulting temperature rises obtained. In the case of tissue these include conduction and perfusion. The characteristics of cavitation in fluid media are also briefly covered. Finally, secondary nonlinear physical effects are described. These include radiation forces on interfaces and streaming in fluids.     

Photomechanical wave-assisted molecular delivery in oral biofilms

Photomechanical waves (PW), the product of an intense light beam interaction with a target material, enhance molecular delivery across biological membranes and skin. The ability to deliver methylene blue (MB), a fluorescent probe and photosensitizer, into bacterial biofilms was demonstrated by applying PW on saliva-derived multi-species biofilms that were developed on agar surfaces in 24-well plates. PW were generated with a Q-switched Nd:YAG laser and were directed into the biofilms in the presence of 25 μg/ml MB. The biofilms were then irradiated with red light at 665 nm. After illumination, adherent bacteria were scraped and spread over the surface of blood agar plates. Survival fractions were calculated by counting bacterial colonies. Microbial analysis was performed via a colony lift method and a DNA checkerboard assay using whole genomic probes to 40 oral microorganisms. Visual analysis by confocal scanning laser microscopy demonstrated that the application of PW enhanced the penetration depth of MB in biofilms. Exposure to MB, PW and light led to a significant reduction of the mean levels of log₁₀ CFU counts compared with the group that received MB and light (P = 0.006). The DNA checkerboard assay showed some benefit from PW-assisted phototargeting in 25 biofilm microorganisms relative to phototreatment alone. Our data provide a basis for further exploration and optimization of PW parameters for complete eradication of microorganisms in oral microcosm biofilms.     

甘蓝型油菜PEP基因片段的克隆和种子特异性反义表达载体的构建及转基因油菜的获得

丙酮酸羧化酶(PEP)是控制油菜蛋白质/油脂含量比例的一个种子的含油量.本研究利用PCR法从甘蓝型油菜花油5号(H045)克隆了PEP基因片段,并与载体pBI121-B构建了反义PEP基因的种子特异性植物表达载体,通过激光微束穿刺法将其转化到甘蓝型油菜中,目前已获得了转基因植株.     

Effects of 11-month interventions on oral cleanliness among the long-term hospitalised elderly

Objectives: This trial studied the effects of interventions on the oral cleanliness of the long‐term hospitalised elderly. Background: Oral cleanliness is mostly poor in long‐term facilities. While many agree on the importance of oral hygiene education for nursing personnel, little information and agreement exists on how to organise this education in geriatric institutions. Materials and methods: This is a longitudinal study with interventions. After a baseline clinical examination, the patient wards were divided into three groups (A, B and C) and the type of intervention was randomly assigned. In group A, dental hygienists provided oral hygiene measures for the subjects once every 3 weeks. In group B, the nursing staff first received hands‐on instructions after which they assumed responsibility for the subjects’ daily oral hygiene. Group C served as a control. Denture hygiene and dental hygiene were recorded at baseline and in the end of the 11‐month study period. In total, 130 subjects completed the interventions; their mean age was 82.9 years. Results: The best outcome in both denture and dental hygiene occurred when nursing staff at the wards took care of hygiene (group B). The increase in the proportion of those with good denture hygiene was the most prominent in group B (from 11% to 56%). The proportion of subjects with poor overall dental hygiene decreased from 61% at baseline to 57% in the end, for group B from 80% to 48%. Conclusions: Organised oral health education of the nursing staff should receive more attention.     

Hyperparathyroïdie primaire : confrontation scintigraphie parathyroïdienne TEMP-TDM au MIBI-Tc99m aux données histologiques

BackgroundPrimary Hyperparathyroidism is a common endocrinopathie whose parathyroid scintigraphy is part of its preoperative assessment. Our aim was to compare our results of scintigraphy with single-photon emission tomography coupled with a scanner (SPECT-CT) with the operative data and in particular histological data.MethodsRetrospective study including 46 patients who underwent surgery for hyperparathyroidism and had a positive parathyroid scintigraphy and in whom the definitive operative and histological reports are available.ResultsThe mean age was 56.7 years with a sex ratio of 0.12. The median parathyroid hormone (PTH) was 246 pg./ml with mean serum calcium of 113.5 mg/ml. The sensitivities of cervical ultrasound, planar scintigraphy and SPECT-CT were respectively 50 %, 89.12 % and 95.65 %. A SPECT-CT had a better sensitivity in patients with a nodular thyroid or ectopic or infracentimetric adenoma. Surgical exploration was unilateral in 69.5 % of cases. Intraoperative PTH was reduced by more than 50 % in 95 % of patients. As for the histology, considered the gold standard diagnostic examination, it concluded that a parathyroid adenoma was found in 45 patients. The resected parathyroid parenchyma was normal in a single patient despite the hypertrophic appearance.ConclusionThe main contribution of SPECT-CT is the accurate localization of ectopic hyper functional glands, thus selecting patients for unilateral or minimally invasive cervical surgery and reducing the rate of therapeutic failure. It has also better results than planar scintigraphy in small parathyroid glands and in cases associated to nodular thyroids.     

Wine grape pomace flour improves blood pressure,fasting glucose and protein damage in humans: a randomized controlled trial

Background

The Mediterranean diet is a healthy diet with positive scientific evidence of preventing chronic diseases. Bioactive components support the healthy properties of the Mediterranean diet. Antioxidants and fiber, two components of the Mediterranean diet, are key functional nutrients for healthy eating and nutrition. Wine grape pomace is a rich source of these dietary constituents and may be beneficial for human health. Our hypothesis was that the intake of red wine grape pomace flour (WGPF) prepared from red wine grapes (Cabernet Sauvignon variety) reduced the metabolic syndrome in humans. To evaluate the effect of WGPF on components of metabolic syndrome we design a 16-week longitudinal intervention study. Thirty-eight males, 30–65 years of age, with at least one component of metabolic syndrome, were randomly assigned to either the intervention group (n = 25) or the control group (n = 13). At lunch, the intervention group was given 20 g of WGPF per day, which contained 10 g of dietary fiber, 822 mg of polyphenols and an antioxidant capacity of 7258 ORAC units. Both groups were asked to maintain their regular eating habits and lifestyles. Clinical evaluation, anthropometric measurements and biochemical blood analyses were done at the beginning and the end of the study.

Results

WGPF intake significantly decreased systolic and diastolic blood pressure as well as fasting glucose levels. Plasma γ-tocopherol and δ-tocopherol increased and carbonyl group in plasma protein decreased in WGPT group, significantly. No significant effect was observed for waist circumference, HDL cholesterol, triglycerides, total antioxidant capacity and vitamin C in and between groups. The group-dependent magnitude of the differences between the baseline and final postprandial insulin values and γ-tocopherol concentrations was statistically significant.

Conclusions

The consumption of WGPF-rich in fiber and polyphenol antioxidants, as a food supplement in a regular diet improves blood pressure, glycaemia and postprandial insulin. In addition, increased antioxidant defenses and decreased oxidative protein damage indicating attenuation of oxidative stress. WGPF might be a useful food ingredient for health promotion and chronic disease prevention.