In vitro phonophoresis: effect of ultrasound intensity and mode at high frequency on NSAIDs transport across cellulose and rabbit skin membranes.

The objective of this study was to evaluate the effect of intensity, mode, and duration of ultrasound application on the transport of three nonsteroidal anti-inflammatory drugs (NSAIDs) across cellulose membrane and rabbit-skin. Ibuprofen, piroxicam and diclofenac sodium were used as the model drugs. Studies were performed in vitro using a modified Franz diffusion assembly adapted to a therapeutic ultrasound transducer. Ultrasound had a significant and positive effect on the transport of the model NSAIDs across cellulose and rabbit skin membranes. Increasing ultrasound intensity from 0.5 to 3.0 W/cm2 led to a proportional increase in drug transport. Continuous ultrasound mode was more effective in enhancing drug transport than the pulsed mode. Diclofenac sodium had the least flux and permeability coefficient. This was attributed to its comparatively lower pKa value that renders the drug more ionizable in the buffer solution, consequently reducing its selective penetration through the membranes. This study demonstrated the therapeutic potential of ultrasound in transdermal delivery of NSAIDs and the synergistic effect of temperature and ultrasound operational parameters on drug transport.

Assessment of aortic valve stenosis severity: A new index based on the energy loss concept.

BACKGROUND: Fluid energy loss across stenotic aortic valves is influenced by factors other than the valve effective orifice area (EOA). We propose a new index that will provide a more accurate estimate of this energy loss. METHODS AND RESULTS: An experimental model was designed to measure EOA and energy loss in 2 fixed stenoses and 7 bioprosthetic valves for different flow rates and 2 different aortic sizes (25 and 38 mm). The results showed that the relationship between EOA and energy loss is influenced by both flow rate and aortic cross-sectional area (A(A)) and that the energy loss is systematically higher (15+/-2%) in the large aorta. The coefficient (EOAxA(A))/(A(A)-EOA) accurately predicted the energy loss in all situations (r(2)=0.98). This coefficient is more closely related to the increase in left ventricular workload than EOA. To account for varying flow rates, the coefficient was indexed for body surface area in a retrospective study of 138 patients with moderate or severe aortic stenosis. The energy loss index measured by Doppler echocardiography was superior to the EOA in predicting the end points, which were defined as death or aortic valve replacement. An energy loss index

A programmable drug delivery system for oral administration.

A programmable, controlled release drug delivery system has been developed. The device in the form of a non-digestible oral capsule (containing drug in a slowly eroding matrix for controlled release) was designed to utilize an automatically operated geometric obstruction that keeps the device floating in the stomach and prevents it from passing through the remainder of the GIT. Different viscosity grades of hydroxypropyl-methyl-cellulose were employed as model eroding matrices. The duration during which the device could maintain its geometric obstruction (caused by a built-in triggering ballooning system) was dependent on the erosion rates of the incorporated polymers (the capsule in-hosed core matrix). After complete core matrix erosion, the ballooning system is automatically flattened off so that the device retains its normal capsule size to be eliminated by passing through the GIT. In vitro long-term drug delivery from a prototype model was studied using levonorgestril as a model drug. Zero-order release could be maintained for periods ranging between 5 and 20 days before the geometric obstruction is triggered off. The rate of drug release was dependent on the nature, viscosity and ratios of polymer employed.

A new flow model for Doppler ultrasound study of prosthetic heart valves.

BACKGROUND AND AIM OF THE STUDY: Steady and pulsatile flow models used to assess the hydrodynamic aspects of prosthetic heart valves are generally made of Plexiglas and Lucite tubing. They often allow continuous-wave and pulsed-wave Doppler ultrasound velocity measurements to be made parallel to the flow, but cannot be used as such for ultrasound scanning of valve inflow and outflow velocities because of ultrasonic reverberation and refraction by the tubing. The aim of the study was to develop a new flow model which allowed ultrasonic scanning of the prosthetic valve flow for three-dimensional (3D) reconstruction of color Doppler flow distributions. METHODS: The flow model, designed with left ventricular and aortic chambers composed of agar gel which mimics the ultrasound characteristics of biological tissues, was developed and tested for comparative in vitro hydrodynamic and Doppler ultrasonic studies of aortic prosthetic valves. An electromagnetic flowmeter and a pressure monitor provided the flow and pressure signals for the hydrodynamic tests. The Doppler ultrasonic evaluation was performed with an Ultramark 9 HDI ultrasound system and a 3D ultrasound imaging system. The model was designed to enable assessment of prosthetic valve performance by pulsed-wave and continuous-wave Doppler velocity measurements, as well as by 3D color Doppler velocity measurements obtained by ultrasonic scanning of the left ventricle or aortic chamber with an ultrasound probe mounted on a motorized translation assembly. RESULTS: The study results showed that this new flow model can provide 3D color Doppler velocity distributions as well as accurate comparisons of hydrodynamic parameters of mechanical and bioprosthetic heart valves derived from Doppler and catheter measurements, both under steady and pulsatile flow conditions. CONCLUSION: This new flow model can be used to evaluate the usefulness of hydrodynamic parameters for the assessment of prosthetic heart valves using both conventional Doppler echocardiography, as currently used in patients, and 3D color Doppler ultrasonic imaging.

Presence of a novel nuclear lamina protein in Raji cells.

In mammalian tissues, the nuclear lamina is composed of the major lamins A, B, and C, and minor lamins D/E. Although lamin B is present in all cell types, lamins A and C are absent from embryonic cells and most undifferentiated cells from hematopoietic lineage. We have investigated the nuclear lamina protein composition of the Raji cell line, lymphoblast-like cells established from a Burkitt lymphoma patient. Lamins A and C were confirmed absent by immunodetection and Northern blot analysis. Besides lamins B and D/E, a protein migrating around 71 kilodaltons was recognized by a serum directed against the nuclear lamina of BHK-21 fibroblasts. Cellular localization by sequential extraction established this 71-kilodalton protein as an exclusive component of the nuclear lamina fraction. These results indicate that the nuclear lamina has a more complex composition than previously thought to be the case for cells devoid of lamins A and C.

Nuclear matrix protein mitotin messenger RNA is expressed at constant levels during the cell cycle.

During the course of an investigation on nuclear matrix protein cDNAs, we have isolated a cDNA clone hybridizing with the messenger RNA encoding mitotin. Mitotin is a 125 kDa/pI 6.5 nuclear matrix protein present in proliferating but not in resting cells. This protein was shown to have a marked increase and characteristic redistribution in G2/M phase of the cell cycle. In this report, using synchronized Raji and WISH cells, we demonstrate that mitotin messenger RNA is expressed at the same level throughout the cell cycle.

Expression of nuclear matrix proteins in rat liver tissue.

We have studied the synthesis of nuclear matrix proteins as it occurs in the rat liver. To investigate their kinetics in tissue, nuclear matrix proteins were prepared from liver of rats injected with radioactive methionine. Synthesis of lamins was not observed in quiescent hepatocytes although they were the principal proteins of this subcellular fraction, suggesting that lamins are very stable in the liver. When hepatocytes were stimulated to divide by partial hepatectomy, only synthesis of lamin B was initiated. Many proteins not visible on Coomassie blue-stained gels were detectable by autoradiography. In the nuclear matrix extracts of quiescent hepatocytes, one of the most prominently labeled ones was a protein of 70 kDa. After hepatectomy, an additional protein of 62 kDa was detectable. These proteins were visible 1 h after the injection of radioactivity, but were no longer observed in nuclear matrices prepared 24 h after injection. These experiments indicate that in addition to lamins, two nuclear matrix proteins are present in the rat liver that were not detected previously, perhaps because of their rapid turnover.

A 165 kd protein of the herpes simplex virion shares a common epitope with the regulatory protein, ICP4.

We have investigated the possibility that immediate-early (IE) protein ICP4 could be a part of herpes simplex virus type 1 (HSV-1) virion particle. Immunodetection with a monoclonal antibody against ICP4 reveals that a component of the virion, migrating at 165 kd, shares a common epitope with this immediate-early protein. Immunolocalization studies on purified virions indicate that the antigen can be detected only in virions without membranes, and is located outside the capsid, most probably in the tegument. Ultrastructural localizations on HSV-1 infected BHK cells extracted with a nonionic detergent confirm that the protein immunoreacting with anti-ICP4 is present in virions.

In vitro release and in vivo absorption of nitrofurantoin and nalidixic acid from ethylcellulose microcapsules.

Ethylcellulose was used as an efficient retarding material to prepare nitrofurantoin or nalidixic acid microcapsules. The dissolution rates of the different preparations have found to increase in alkaline rather than in acidic media. Considerable retardation in the rate and extent of release from 2:1, 1:1 and 1:2 drug-polymer ratios were observed as compared with those of the plain drugs. Absorption study in man proved that formulations containing 2:1 ratios have delayed urinary excretion rates by 2 h, however, the total cumulative amounts excreted from all samples remained almost constant. Man volunteers administered the 2:1 drug-polymer microcapsules did not suffer gastric irritation, usually produced after three consecutive d from taking the plain drugs. Experiments in male albino rats showed that the coated drugs did not produce gastric hemorrhage seen with the same doses of the uncoated ones.