Quantifying the effects of standing waves within the skull for ultrasound mediated opening of the blood-brain-barrier

Ultrasound mediated opening of the blood-brain barrier (BBB) has been shown to be effective in enhancing the delivery of therapeutic agents to the brain. However, challenges remain in targeting and specificity of BBB opening due to attenuation, aberration and reverberation of transcranial ultrasound fields. In this study, experimental and numerical assessment was performed of standing waves within an ex vivo human skull when delivering ultrasound pulses of varying lengths at 300 kHz using a large aperture focused ultrasound transducer. Simulations showed minimal distortion of the focal region but low amplitude standing waves were established within the skull with bursts of 50 cycles or more. Under the same conditions, the experimental measurements showed small variations in focal pressure which took 300 to 600 µs to stabilise. The pattern of sidelobes and superimposed standing waves was generally more complex when the focus was placed closer to the side and base of the skull. This data supports the use of large aperture diameter transducers and short pulse lengths for targeted BBB opening

An analysis of the acoustic cavitation noise spectrum: The role of periodic shock waves

Research on applications of acoustic cavitation is often reported in terms of the features within the spectrum of the emissions gathered during cavitation occurrence. There is, however, limited understanding as to the contribution of specific bubble activity to spectral features, beyond a binary interpretation of stable versus inertial cavitation. In this work, laser-nucleation is used to initiate cavitation within a few millimeters of the tip of a needle hydrophone, calibrated for magnitude and phase from 125 kHz to 20 MHz. The bubble activity, acoustically driven at f0 = 692 kHz, is resolved with high-speed shadowgraphic imaging at 5 × 106 frames per second. A synthetic spectrum is constructed from component signals based on the hydrophone data, deconvolved within the calibration bandwidth, in the time domain. Cross correlation coefficients between the experimental and synthetic spectra of 0.97 for the f 0/2 and f 0/3 regimes indicate that periodic shock waves and scattered driving field predominantly account for all spectral features, including the sub-harmonics and their over-harmonics, and harmonics of f 0

Storage of milk powders under adverse conditions: 2. Influence on the content of water-soluble vitamins

1. Storage of milk powder under unfavourable conditions accelerates the normally slow deterioration in nutritional quality. The effects of such storage on the water-soluble vitamin composition were examined. 2. (a) Spray-dried whole milk containing 25 g water/kg was stored at 60° and 70° and sampled weekly to 9 weeks. (b) Spray-dried whole milk and skimmed milk were adjusted to contain 40 and 100 g water/kg and stored at 37° in nitrogenand in oxygen. Samples were taken for analysis at intervals during storage. 3. The samples were analysed for eight B-complex vitamins and ascorbic acid, and also for total lysine, ‘reactive lysine' and ‘lysine as lactulosyl-lysine'. 4. Storage at 60° caused rapid destruction of folic acid (53% loss at 4 weeks) and slower loss of thiamin, vitamin B6 and pantothenic acid (18% at 8 weeks). There was no change in the content of riboflavin, biotin, nicotinic acid and vitamin B12. At 70° the rate of destruction of the four labile vitamins was much increased; 18% or less survived at 4 weeks. 5. At 37° and 40 g water/kg there was little change in total and ‘reactive' lysine during storage for 57 d. Lactulosyl-lysine was demonstrably present butatlow concentration. There was considerable loss of folate (72%) and ascorbate (91%) during storage for 30 d in O2, but no significant loss in N2. Thiamin fell by approximately 12% in 57 d, equally in O2 and N2. The content of the remaining vitamins was unchanged. At 100 g water/kg there were progressive Maillard changes. During 27 d in N2 the colour changed from cream to palebrown, but in O2 there was no perceptible colour change. Total lysine fell by 20% in 27 d, and ‘reactive lysine' by 30%. Folate was stable during 16 d in N2, but largely (94%) destroyed in O2. Ascorbic acid was also destroyed in N2 as in O2. Thiamin fell by 41% in 27 d, equally in O2 and N2. Vitamin B6 was more labile, especially in N2, falling by 71% in 16d. 6. With skimmed-milk powder containing 100 g water/kg, storage at 37° in O2 and N2 gave much the same results as for the corresponding whole-milk powder. The presence of milk fat had no marked effect on the stability of the water-soluble vitamins. 7. Destruction of vitamins was clearly linked to the progress of Maillard-type reactions and was strongly influenced by time and temperature of storage, moisture content and, in some instances, by the presence of O

Storage of milk powders under adverse conditions: 1. Losses of lysine and of other essential amino acids as determined by chemical and microbiological methods

1. Whole-milk powders containing 25 g water/kg were stored for up to 9 weeks in sealed aluminium containers at elevated temperatures. Lysine and other essential amino acids were measured by chemical and microbiological methods. 2. Storage at 60° resulted in the progressive formation of lactulosyl-lysine. After 9 weeks, 30% of the lysine groups were present in this form. The powders still retained their natural colour and the levels of tryptophan, methionine, cyst(e)ine and leucine remained unchanged. 3. Storage at 70° resulted in the formation of lactulosyl-lysine followed by its complete degradation with the development of browning. Available tryptophan, methione, leucine and isoleucine decreased progressively during storage. 4. The different methods for lysine determination gave widely dissimilar results. The direct fluorodinitrobenzene (FDNB) technique and reactive lysine from furosine were considered to be the most reliable methods. The FDNB-difference, dye-binding lysine, Tetrahymena and Pediococcus methods all seriously underestimated reactive or available lysine in heat-damaged milk powders. Tetrahymena and Pediococcus appeared to utilize lactulosyl-lysine as a source of lysine. 5. The results are discussed in relation to storage and distribution of milk powders in hot climate

Protein-polyphenol reactions: 1. Nutritional and metabolic consequences of the reaction between oxidized caffeic acid and the lysine residues of casein

1. Studies were made on the lysine content of casein reacted with caffeic acid oxidized aerobically under alkaline conditions or enzymically with tyrosinase (EC 1.14.18.1). 2. Loss of fluorodinitrobenzene (FDNB)-reactive lysine was rapid at pH 10 and increased with time and the temperature of the reaction, with concentration of caffeic acid and with the oxygenation of the mixture. In presence of the enzyme mushroom tyrosinase, maximum reduction of reactive lysine occurred at pH 7 and was dependent on the reaction time and on the concentration of caffeic acid. 3. Reaction of α-formyl-L-[U- 14C]lysine with caffeic acid at pH 10 showed the rapid formation of five reaction products which appeared to polymerize gradually as the reaction progressed. 4. The nutritionally available lysine content of the casein-caffeic acid mixtures, as assayed with rats, was reduced after both alkaline and enzymic reactions, as were faecal digestibility, net protein ratio and net protein utilization. Biological value however was not reduced. 5. In metabolic studies using goat milk casein labelled with L-[3H]lysine and reacted with caffeic acid in the same way, the lysine-caffeoquinone reaction products were not absorbed by the rat but were excreted directly in the faeces. 6. The importance of the reaction of proteins with caffeoquinone and chlorogenoquinone (formed by the oxidation of caffeic and chlorogenic acids respectively) is discussed in relation to the production of sunflower protein, leaf protein and other vegetable-protein concentrate

The effect of Maillard reaction products on zinc metabolism in the rat

The effect of giving Maillard reaction products (MRP) on zinc metabolism was investigated in the rat. In Expt 1, MRP were prepared by incubating casein with either glucose or lactose under controlled reaction conditions, and were quantified as either ‘early' or ‘advanced' after estimation of lysine loss and lysine destruction respectively. In Expt 2, the effect of the purified early MRP fructose-lysine (FL) on Zn metabolism was studied. The experimental diets containing 20 mg Zn/kg were given to weanling rats for 21 d. Zn balance was assessed over 9-14 d (Expt 1), or 1-14 d (Expt 2). Femur, liver, kidney and serum Zn concentrations were determined at 21 d. The major effect of the MRP in the casein-sugar mixtures was on urinary Zn excretion. The casein-glucose MRP induced up to a 6-fold increase in the quantity of Zn excreted in the urine. The magnitude of the hyperzincuria increased with the extent of the Maillard reaction. Similar dietary levels of casein-lactose MRP increased urinary Zn loss 2-fold. Free FL had no effect on urinary Zn. Faecal Zn, Zn retention, liver, femur and serum Zn were generally not influenced by giving MRP from casein-sugar mixtures or by giving free FL, although kidney Zn was decreased in rats fed on FL. It was concluded that although urinary Zn excretion can be increased by the presence of MRP in the diet, this is only a minor excretory pathway and would have little influence on overall Zn nutrition in individuals fed on a diet adequate in Z