Application of the quantitative detection of a change in concentration of magnesium stearate in a feeder tube of tableting manufacture by real-time near-infrared spectroscopy.

Process analytical technology is important for the analysis and control of manufacturing processes. Near-infrared spectroscopy is widely used in various process analytical technologies for the analysis of the chemical componentsof solid dosage forms. Lubrication is an important process carried out before a tablet is produced. In this process, the concentration of lubricant, such as magnesium stearate (StMg), might change for one of many reasons during powder transport, which would be a critical problem such as variation in tablet compressibility and dissolution failure of compressed tablets. Our group investigated the feasibility of the quantitative monitoring of a change in the concentration of StMg in the feeder tube of tableting equipment employing real-time near-infrared spectroscopy.

Strategic development of a multivariate calibration model for the uniformity testing of tablets by transmission NIR analysis.

The use of transmission near infrared spectroscopy (TNIRS) is of particular interest in the pharmaceutical industry. This is because TNIRS does not require sample preparation and can analyze several tens of tablet samples in an hour. It has the capability to measure all relevant information from a tablet, while still on the production line. However, TNIRS has a narrow spectrum range and overtone vibrations often overlap. To perform content uniformity testing in tablets by TNIRS, various properties in the tableting process need to be analyzed by a multivariate prediction model, such as a Partial Least Square Regression modeling. One issue is that typical approaches require several hundred reference samples to act as the basis of the method rather than a strategically designed method. This means that many batches are needed to prepare the reference samples; this requires time and is not cost effective. Our group investigated the concentration dependence of the calibration model with a strategic design. Consequently, we developed a more effective approach to the TNIRS calibration model than the existing methodology.

[An approach to home therapy for cancer pain patients].

Recently, in consideration of cost performance and improvement in quality of life (QOL) of the patient, the significance of home care and outpatient treatment has also been recognized in Japan. A terminal cancer patient who had local recurrence in the pelvic region after surgery for rectum carcinoma, was treated for cancer pain by us with a continuous epidural infusion of morphine by means of a prolonged operating continuous infusion device. The treatment made home therapy possible and allowed the patient to return to normal social activities. Based on this case, the significance of and issues regarding home therapy are discussed in this study.

[The main cause responsible for the disparity between enzymatic and diazo methods in measuring direct bilirubin from a viewpoint of bilirubin subfractionation].

An enzymatic method which measures bilirubin with bilirubin oxidase has come into use but there is often a disparity in the values of direct bilirubin measured by enzymatic and diazo methods. To determine the cause of this disparity, bilirubin subfractions were measured by HPLC. The retention time (mean +/- SD) of each subfraction was: alpha, 34.7 +/- 0.1 min; beta (biphasic), 29.3 +/- 0.1 & 28.6 +/- 0.1 min; gamma, 24.9 +/- 0.1 min; delta, 20.2 +/- 0.3 min. Samples with great difference have all four peaks (alpha + beta + gamma + delta type) while samples with little difference have large alpha and delta peaks with small beta and gamma peaks (alpha + delta type). Therefore, the beta and gamma subfractions (conjugated bilirubin) contribute substantially to the difference. Bile and synthesized direct bilirubin are comprised solely conjugated bilirubin and show a marked difference. This evidence strongly supports the findings in the present study. Next, synthetic direct bilirubin was measured by HPLC before and after the addition of bilirubin oxidase, and the absorbance at 450 nm was found to increase between 2.9 and 3.5 min. Therefore, it appears that the disparity between enzymatic and diazo methods in measuring direct bilirubin comes from the products of conjugated bilirubin by bilirubin oxidase.

Apparent motion determined by surface layout not by disparity or three-dimensional distance.

The most meaningful events ecologically, including the motion of objects, occur in relation to or on surfaces. We run along the ground, cars travel on roads, balls roll across lawns, and so on. Even though there are other motions, such as flying of birds, it is likely that motion along surfaces is more frequent and more significant biologically. To examine whether events occurring in relation to surfaces have a preferred status in terms of visual representation, we asked whether the phenomenon of apparent motion would show a preference for motion attached to surfaces. We used a competitive three-dimensional motion paradigm and found that there is a preference to see motion between tokens placed within the same disparity as opposed to different planes. Supporting our surface-layout hypothesis, the effect of disparity was eliminated either by slanting the tokens so that they were all seen within the same surface plane or by inserting a single slanted background surface upon which the tokens could rest. Additionally, a highly curved stereoscopic surface led to the perception of a more circuitous motion path defined by that surface, instead of the shortest path in three-dimensional space.

[Sequential changes in the left ventricular function during ramp exercise in patients with ischemic heart disease: continuous assessment of the left ventricular radioactivity with wireless telemetric cardiac monitoring system].

The left ventricular function during ramp exercise was assessed using 99mTc-labeled red blood cells and a Wireless Telemetric Cardiac Monitoring System (WTCMS) in 34 patients who received coronary angiography. Sequential changes in the left ventricular ejection fraction (EF) during exercise, were classified into the two types, normal response (up slope pattern) and abnormal response (horizontal, down slope and up-down slope pattern) when defined the response as 5 percent or more increment of EF as normal. Six patients without significant stenosis by coronary angiography showed normal response. Seventeen of 28 patients with coronary disease showed abnormal response (sensitivity 61%). Eight of 11 patients (73%) with coronary disease and normal response showed no redistribution on the stress thallium myocardial scintigraphy. Twelve of 17 patients (71%) with coronary disease and abnormal response showed redistribution by the stress thallium scintigraphy. Horizontal and down slope patterns of EF during exercise were more often noted in the groups with redistribution and multivessel coronary disease. After the exercise, the times to the over shoot was significantly longer in groups with redistribution (p < 0.01) in comparison with groups without redistribution. From these results, we conclude that the monitoring the changes in left ventricular activity during ramp exercise with the WTCMS is a very useful method for the evaluation of the sequential changes in left ventricular function in patients with ischemic heart disease.

Assessment in pig coronary artery of long-lasting and potent calcium antagonistic actions of the novel dihydropyridine derivative mepirodipine hydrochloride.

Ca antagonistic properties of mepirodipine hydrochloride [+)-(3'S,4S)-3-(1'-benzyl-3'-pyrrolidinyl methyl 2,6-dimethyl-4- (m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate hydrochloride, YM-09730-5) were assessed by studying the pharmacological actions and binding characteristics of the drug in the stem coronary artery. IC50 values of YM-09730-5 (3.5 x 10(-10) mol/l) and nifedipine (6.6 x 10(-9) mol/l) for 40 mmol/l K-induced tonic contraction of pig coronary artery indicated that YM-09730-5 was about 20 times more potent than nifedipine in Ca antagonistic action. However, YM-09730-5 showed an onset of inhibitory action 3 to 5 times slower than nifedipine. A 40-min preincubation of the target tissue with YM-09730-5 also inhibited the contractions produced by acetylcholine, histamine, 5-hydroxytryptamine, and high Ca, and pD2' values were between 8.0 and 7.0; while nifedipine was less potent. The specific binding of [3H]nitrendipine to the membrane of pig coronary artery was inhibited by YM-09730-5, thereby indicating that [3H]nitrendipine and YM-09730-5 compete for the similar receptor sites of dihydropyridine-sensitive Ca channels. Suppression of high K-, Ca- and agonist-induced contractions by YM-09730-5 (3 x 10(-9) mol/l-10(-7) mol/l) remained even after washings at 20-min intervals for more than 3 h; and, in particular at a high concentration of YM-09730-5, the suppression was slightly antagonized by excess Ca or a Ca-agonist. The contraction inhibited by nifedipine, on the other hand, was readily restored by several washings.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of beta-blockade and the non-specific effect of bucumolol, a beta-adrenergic blocking agent, on atrioventricular conduction in anesthetized dogs.

The effects of the beta-adrenergic blocking agent bucumolol [dl-5-methyl-8-(2-hydroxy-3-t-butylaminoproxy)coumarin] and its optical isomers were compared with those of propranolol and pindolol on the functional refractory period and the conduction time of atrioventricular (A-V) transmission in dogs. In dogs with intact nerves anesthetized with pentobarbital, bucumolol and propranolol (30 micrograms - 1 mg/kg) prolonged both parameters by blockade of background sympathetic nervous tone to A-V conduction. The optical d- and l-isomers of bucumolol depressed A-V conduction almost in parallel with their beta-blocking actions. In dogs with cardiac sympathectomy and bilateral vagotomy, or pretreated with reserpine, the dromotropic activity was lowered and the beta-blocking dose (30 micrograms - 1 mg/kg) of bucumolol and propranolol had less effect on A-V conduction, while larger doses (3-10 mg/kg) produced additional depression of the conduction. Pindolol, on the other hand, had a positive dromotropic action, reflecting its intrinsic stimulatory action. It is concluded that A-V conduction is affected by the existing tone of sympathetic nervous activity and that bucumolol has no beta-stimulant action and depresses A-V conduction by beta-blockade and by a non-specific action.

Rapid assessment of visual function: an electronic sweep technique for the pattern visual evoked potential.

We have developed an electronic spatial frequency sweep technique for electrophysiological assessment of visual acuity and pattern vision. The technique allows an accurate and reliable measurement of VEPs to a full range of spatial frequencies in just 10 sec. Because the measurements are so rapid, the technique suggests several new improvements in the assessment of visual function. Sweeping spatial frequency linearly and extrapolating the high-frequency region of the VEP spatial-tuning function to zero voltage allows an estimate of acuity which correlates highly with psychophysical estimates of acuity. Variants of the procedure are appropriate for the assessment of refracture error, determination of equality of visual function for the two eyes and of binocular interactions, and for sequential assessment of therapeutic conditions.

Impedance cardiography for the assessment of cardiac function during exercise.

1. Impedance cardiography proved valuable to estimate the stroke volume and other cardiac parameters noninvasively, when the electrical resistivity of the blood was corrected with hematocrit. 2. Cardiac response to graded exercise on a bicycle ergometer up to the maximal load in healthy young and active middle-aged subjects was divided into four phases from the changes in cardiac parameters such as stroke volume, cardiac output, ejection index and height of the atrial wave. 3. The ischemic patients did not tolerate well the exercise after the second phase or drift phase of exercise. 4. Physical training enhanced the cardiac function in work through increase in cardiac output and work load.