Search

Asian soybean rust (ASR), caused by Phakopsora pachyrhizi, is one of the most serious soybean (Glycine max) diseases in tropical and subtropical regions. To facilitate the development of resistant varieties using gene pyramiding, DNA markers closely linked to seven resistance genes, namely, Rpp1, Rpp1-b, Rpp2, Rpp3, Rpp4, Rpp5, and Rpp6, were identified. Linkage analysis of resistance-related traits and marker genotypes using 13 segregating populations of ASR resistance, including eight previously published by our group and five newly developed populations, identified the resistance loci with markers at intervals of less than 2.0 cM for all seven resistance genes. Inoculation was conducted of the same population with two P. pachyrhizi isolates of different virulence, and two resistant varieties, ‘Kinoshita’ and ‘Shiranui,’ previously thought to only harbor Rpp5, was found to also harbor Rpp3. Markers closely linked to the resistance loci identified in this study will be used for ASR-resistance breeding and the identification of the genes responsible for resistance.

Ag electrodes were formed on InGaN/GaN multi-quantum well blue light emitting diode (LED) substrates by using needle-type dispensing of Ag nanoink and the heat treatment as wet processes. The patterns by using the needle-type dispenser system are drawn out of a dot matrix method like an inkjet printer, and thus, arbitrary graphics can be produced. After patterning, the conductive Ag films as electrodes were formed by sintering at 450°C for 30 minutes under the atmospheric conditions. The fabricated LED emitted blue light with a threshold and operating voltage of 3.3 and 4.4 V, respectively. These results suggest that the wet processed Ag electrodes have a potential for use in the production of GaN based LEDs.

In order to reduce weight of a vehicle, application of light metals has increased. Magnesium alloy is very light and has high specific strength compared to other structural metals. SPR (Self Piercing Rivet) joining has been applied mainly for an aluminum alloy in motor industries. However, application of SPR joining to a magnesium alloy is very limited. In this study, SPR joining was carried out with AM50 magnesium alloy sheets. According to the result of joining experiment, cracking easily occurred at the lower sheet due to poor formability of the alloy. Static and fatigue strength of the joint were evaluated under shear tensile loading condition. The crack introduced in SPR process affects on strength of the joint. As a practical way to solve the problem, adhesive aided SPR joining was proposed. Adhesive was spread on the surface and then SPR joining was conducted before its hardening. The maximum shear tensile load of the joint increased by using an adhesive and was strongly influenced by kind of adhesive used. Fatigue strength also improved by using an adhesive. It is proposed that control for deformation due to SPR process at the edge of the joining area could be effective to improve the strength.

The arc-soot (AS) nano-carbon was synthesized by using arc discharge apparatuses which were the conventional arc apparatus and the new twin-torch-arc apparatus. AS synthesized with the conventional arc apparatus contained cocoon-like carbon nano-horn (CNH), dahlia-like CNH, and graphite ball. On the other hand, AS which was synthesized using the new twin-torch-arc apparatus contained mainly cocoon-like CNH and dahlia-like CNH, and contained a little graphite ball. The quality of dispersion was characterized and evaluated by the index of dispersion which was based on a diameter and a number density of catalyst particles. The electrocatalystic activity of the Pt/Ru catalysts was evaluated by the methanol-impregnated paper burning method. If the index of dispersion of the AS was high, then the AS burned violently. In the dispersion process, the optimum dispersion temperature obtained was 150 °C. Some MEAs of DMFC cell consisted of each Pt/Ru–AS catalyst which had different characteristics. It was observed that the power density increased with the index of dispersion. It was suggested that the power density of DMFC increased by 500% with a 350% increase in the index of dispersion. Pt/Ru–AS catalyst used AS, which was synthesized using the new twin-torch-arc apparatus, was better than Pt/Ru–AS catalysts using AS which were synthesized with the conventional arc apparatus to apply for the catalyst of DMFC.

Observation of the chemical properties, such as the composition, distribution, structure, species, and surface reactions of solid materials, has been an indispensable issue in various fields of science and engineering, such as materials chemistry, environmental geochemistry, photochemistry, catalysis, or chemical synthesis. Physicochemical processes in heterogeneous systems involving solid surface interfaces differ from processes in homogeneous media. Physicochemical processes in heterogeneous systems thus require particular attention because of the discontinuity or high free energy of the interfaces. Such processes can be investigated using experimental methods that derive linear or nonlinear responses to external stimuli by a pulsed laser. In this chapter, state-of-the-art laser-based analytical techniques for actinide chemistry at solid–liquid interfaces are reviewed. These techniques range from luminescence spectroscopy for static and dynamic phenomena to surface-sensitive spectroscopy, for example, time-resolved infrared vibrational/luminescence spectroscopy and vibrational sum frequency generation spectroscopy, and subsequent advanced data analyses. The roles of luminescent molecules and complexes as a probe for the interfacial chemistry are discussed along with the relevant photochemical processes, such as energy or electron transfer. Photochemical properties of the f-block elements, especially actinides ions, at solid-liquid interfaces are focused upon because some actinide ions, such as hexavalent uranium and curium, exhibit exotic luminescent and photochemical properties, which would make them versatile probes of photochemistry of solid surfaces.

A bimodal molecular weight distribution, first predicted theoretically in the Monte Carlo simulation of emulsion crosslinking copolymerization [Macromolecules 27 (1994) 3389], is now confirmed experimentally in emulsion copolymerization of styrene/divinylbenzene, by setting the number of divinylbenzene molecules per primary chain ca. 5. It was found that the locations of these two peaks can be controlled independently, i.e. the location of high molecular weight peak is controlled by the particle size, while that for low molecular weight peak is controlled by the chain lengths of the primary polymer molecules.

A typical behavior of microgel formation in emulsion polymerization, where a sufficient amount of crosslinker exists and no coagulation of particles occurs, is considered both theoretically and experimentally. It was found that the crosslinked polymer formation in emulsion polymerization is significantly different from that in homogeneous media. The important characteristics can be summarized as follows. (1) The crosslinking density level is fairly high even from very early stages of polymerization, (2) the weight-average molecular weight increases just linearly with monomer conversion, and (3) the formed molecular weight distribution (MWD) is rather narrow and the distribution shifts to larger molecular weights with preserving the narrow profile as polymerization proceeds. In a typical microgel formation in emulsion polymerization, each polymer particle essentially consists of a single crosslinked polymer molecule once stable polymer particles are formed.

The prognosis of patients with early re-ruptured intracranial aneurysms is discouraging. We compared the data on patients suffering re-rupture before the onset of late vasospasm (Early-Re) with those suffering rebleeding thereafter (Late-Re). The operability in the Early-Re group was lower (p0.05) and the outcome less satisfactory than that of Late-Re group. Of the Early-Re patients, 83% had a re-rupture within 24 hours of the initial subarachnoid haemorrhage; moreover 46% of these experienced rebleeding within three hours of the initial bleeding. Cases in the Early-Re group tended to belong to Hunt-Hess grade III or IV on admission, of wide spread subarachnoid haemorrhage on CT and of "bump" type aneurysms on angiograms. Based on our experience we propose that early re-rupture may be attributable to the following factors: a gradual and progressive thinning of the wall of bump type aneurysms results in such a large laceration through the fundus of the aneurysm. Re-rupture may occur within a short period after the first rupture because the fibrin net covering the wide laceration cannot tolerate the slight increase in internal pressure within the aneurysmal dome. Therefore, in the patients of Hunt-Hess grade III or IV, conventional angiography, tight holding during CT examination and lumbar puncture, should be avoided during the first three hours after the first bleed. Although early direct operations on patients with high Hunt-Hess grades tend to produce an unsatisfactory outcome, we cannot help these patients with Early-Re without surgical treatment. Not only early direct operation but also first conservative treatment to control systolic blood pressure are very important in patients with Early-Re.

Inter-laboratory reproducibility of representative release tests, namely paddle, Muranishi and dialysis tubing methods for suppositories were investigated using two kinds of suppositories of indomethacin, oily and water-soluble types. The inter-laboratory differences for the water-soluble suppository determined by paddle and modified Muranishi methods were small whereas the differences for the oily suppository determined by Muranishi and dialysis tubing methods were large. The release rate of oily suppository by Muranishi method was significantly reduced when the cylindrical cell containing suppository was placed slightly lower. The release rate by dialysis tubing method was decreased by addition of a small volume of test fluid into the dialysis tube. These variables probably contributed to the inter-laboratory differences for the oily suppository. Neither Muranishi or dialysis tubing method should be employed for quality control of oily suppositories unless their reproducibility is significantly ...

We investigated the hydrodynamic flows around tablets during several pharmacopeial dissolution tests: the rotating basket (RB), paddle (PD), flow-through cell (FT), and disintegration (DI) tests. The determination of hydrodynamic flow was based on the dissolution rate of United States Pharmacopeial salicylic acid nondisintegrating calibrators, and showed that, compared with the PD and RB methods, the FT method produced a lower hydrodynamic flow value whereas the DI method produced a higher value. The hydrodynamic flows during the PD and RB tests appeared to be similar at the same rotational speed, although the flow patterns around the tablet differed; with the RB method, homogeneous dissolution occurred from all surfaces of the tablet, while with the PD method, dissolution from the lower surface was slower. The use of a sinker seemed to enhance dissolution from the lower surface. Such differences in hydrodynamic flow could explain the apparently different dissolution behaviors of disintegrating prednisone and nondisintegrating acetaminophen tablets when assessed by the PD and RB methods. These differences in hydrodynamic flow between in vitro tests should be considered when choosing dissolution tests for studying in vitro/in vivo relationships and for quality control purposes.

A clinically tonic seizure phase, immediately followed by psychomotor features (right hand dystonic posture, left hand and oral automatisms), was recorded by video and EEG, in a patient who had gliosis of the left temporal lobe and left hippocampal atrophy. Interictal epileptiform discharges were frequently seen in the left temporal area, and at the time of the tonic seizure phase, ictal spike discharges were continuously observed at the left posterior temporal area, which was recognized only by applying a high frequency filter (HFF) of 15 Hz to the digitally recorded EEG because EMG artifacts totally obscured the EEG with a HFF of 60 Hz. It is most likely that tonic seizure can occur in an adult patient with temporal lobe epilepsy, and it is speculated that an epileptogenic focus might activate a certain brain area which is regarded as a symptomatogenic zone for tonic seizures. If the tonic seizure phase is immediately followed by psychomotor features as seen in the present patient, the former could be due to focal epilepsy.

The collaborative study participated by seven laboratories was carried out to develop a dissolution standard for evaluating vibration levels of dissolution apparatuses using enteric-coated granules of cefalexin (EG). Dissolution apparatuses could be divided into two groups according to their vibration levels and the dissolution test results of EG by the rotating basket method at 50 rpm. The critical value of acceleration was about 0.05 m/s2. The upper limit of normal dissolution rates of EG was calculated from the results of the rotating basket method at 50 rpm obtained from low vibration apparatuses. All high vibration apparatuses used in this study were distinguished by the limit from low vibration apparatuses, although most of them were not distinguished by current USP calibrators. These results suggest that EG would be useful as a calibrator for detection of apparatuses on high vibration levels.

A boy with Down syndrome who developed myelodysplastic syndrome after regression of transient abnormal myelopoiesis (TAM) is described. His blast cells in TAM had other chromosome abnormalities in addition to trisomy 21;50,XY,+21c,+12,+14,+21. Serial chromosome analysis in follow-up showed abnormal clones involving monosomy 7. Myelodysplastic syndrome was diagnosed. Because two clones had different karyotypes, they might have derived from different clones.

We identified a DNA polymerase species in Drosophila melanogaster embryos, and purified it. This polymerase shared some common properties with DNA polymerase epsilon from mammals and yeast as follows; it has a preference for poly(dA)/oligo(dT) as a template/primer, it is highly processive in DNA synthesis, it co-fractionates with 3'-5' exonuclease activity, it is sensitive to aphidicolin and is resistance to ddTTP. The polymerase activity was inhibited in the immuno-precipitation assay with anti-pol-epsilon antibodies, which were produced against a polypeptide coded on the cDNA of a putative Drosophila pol-epsilon we isolated previously. Using these antibodies, Western blot analysis revealed that this polymerase is a 250kDa polypeptide, which is the same size as observed in mammals and yeast. These results indicate that Drosophila produces the epsilon-class of DNA polymerase, and like mammals or yeast, possesses the 5 typical classes of DNA polymerases (alpha to epsilon) in its embryos.

The criteria of Content Uniformity test and Weight Variation test in JP 13 were greatly changed to reduce consumer's risk. The new criteria were set to keep the rate of defectives in lots passing the tests less than the acceptable rate. However, in some cases, the new criteria can not directly be applied to some formulations and several modifications are needed in the criteria. In this report, the several resolution of this problem are represented. The applicability of these tests for in-process tests is also discussed.

This study examined the effects of mechanical destructive forces on drug release from controlled release (CR) multiple unit dosage forms in vitro and in vivo and their colonic release, using two CR granules of acetaminophen, AG and BG, which differed in hardness (AG was hard and BG was soft), but which did not depend on agitation speed or pH for their release.In vitro release rates were determined using several official methods and the rotating dialysis cell method. Granules were administered to healthy volunteers under fasting and fed conditions.Both granules showed similar release rates under mild destructive conditions in official dissolution tests, but BG showed a faster release rate in the rotating dialysis cell method. In the fasting state, the drug absorption-time profiles of AG and BG were almost equal. In the fed state, the drug release rate of BG increases whereas that of AG is almost equal to the fasted state. The food effect on BG could be caused by an increase in the mechanical stress of the GI tract due to food intake judging from the findings in vitro and in dogs. The colonic release from multiple unit CR products was larger than that from single unit ones.In vivo release of drug from a multiple unit CR product that is structurally weak is affected by mechanical stresses, which differ among human subjects but are increased by food ingestion. Colonic release from multiple unit CR products is larger than that from single unit products.

Bioequivalence tests in Japan are now under the improvement according to the WHO guidance. This article describes the desirable assessment of bioequivalence where the use of discriminatory subjects, application of confidence interval methods, logarithmic transformation of pharmacokinetic data are recommended. The role of dissolution tests in bioequivalence assessment is also discussed.

This study was undertaken to examine the effects of mechanical destructive forces on drug release from controlled release (CR) dosage forms in vitro and in vivo and their colonic release, using two CR tablets of acetaminophen A and B, showing slower and faster erosion rates, respectively.In vitro release rates were determined by several official methods. Tablets were administered to healthy volunteers under fasting and fed conditions.Both tablets showed similar release rates under mild destructive conditions (e.g., paddle method at 10 rpm) but CR-B showed faster release under highly destructive conditions (e.g., rotating basket method at 150 rpm), where the tablet was eroded. The in vivo release from CR-B was faster than from CR-A, possibly because of enhanced erosion. The variable in vivo release from CR-B indicated large inter-subject differences in destructive GI forces. The fastest in vivo release from CR-B among individuals was approximated by the in vitro dissolution determined by destructive methods such as the rotating basket at 150 rpm. The slowest in vivo release from tablets A and B was lower than the dissolution by the paddle method at 10 rpm. The release from both tablets was markedly reduced at 3-4 hrs after dosing irrespective of feeding conditions which can be attributed to release inhibition in the colon.Effects of GI destructive forces on the tablet erosion and the release inhibition in the colon must be considered in the development of CR dosage forms.

In this study, we assessed the hydrodynamic flow around a dosage form in the GI tract in humans by comparing the characteristics of in vitro and in vivo release of two different types of controlled release acetaminophen (paracetamol) tablets, A and B. The former tablet showed an agitation speed-dependent release at a high speed range (50-100 rpm), whereas the latter showed this characteristic at a low speed range (10-50 rpm). The mean release amount-time profiles of tablets A and B in humans showed biphasic characteristics, and the first phase of the absorption profiles of A and B was close to their in vitro profiles at a paddle speed of 10 rpm. The in vivo profiles were also superimposable on in vitro dissolution curves obtained by the flow-through cell method at a flow rate of 1 mL/min (velocity 0.89 cm/min) or less. These results indicate that the hydrodynamic flow around the dosage forms in the human GI tract could be extremely low. The in vivo release rate of these tablets in dogs was greater than in humans, and was estimated to be equivalent to the release rate determined by the paddle method at 100 rpm. This indicates that a higher agitation intensity in the GI tract in dogs than in humans may be one cause of the discrepancies between humans and dogs in drug absorption studies.

Introduction Beads based multiplex assays are useful to detect biomarkers that characterize specific diseases in a single experiment using relatively small amounts of patient’s serum. In this study, our aim was to explore the possibility of establishing a cytokine/chemokine profile for diseases by determining the cytokine/chemokine values in healthy subjects then do a comparison with the values of diseased subjects. We hypothesized that in this way, we may be able to observe which cytokine/chemokines are elevated or suppressed and use this data to create a profile for various diseases. To this end, using influenza and Castelman’s disease as an example, we determined and compared the plasma levels of 27 cytokines/chemokines in 52 healthy individuals, 9 patients with H1N1 influenza and 15 patients with Castleman’s disease. Methods Using Bio-Plex Pro 27 panel, patients’ cytokine/chemokine levels were determined and analyzed. First, we sorted the cytokine/chemokine values of healthy individuals in descending order and found that, except for the first 5 values, 90% of healthy individuals had chemokine/cytokine values that became relatively stable below a certain range. Using these values, we determined an upper limit for each cytokine/chemokine that is considered normal in healthy subjects and compared these upper limits with the cytokine/chemokine values in diseased patients in order to create a profile for influenza and Castleman’s disease. Setting the upper limits for healthy subjects as the base value, we measured chemokine/cytokine in influenza and Castleman’s disease patients to determine if their values exceed the normal upper limit of healthy individuals. If any particular cytokine/chemokine was elevated in more than two-thirds of the patients we considered that particular cytokine/chemokine as being a possible biomarker for influenza or Castleman’s disease. Results In influenza patients, serum IL-6, IP-10, MCP-1, MIP-1b and RANTES had values that exceeded the upper limit of healthy individuals. IP-10 in particular, had levels that were more than 10 times higher. In more than two-thirds of patients with Castleman’s disease, IL-6, IL-8, IL-13, IL-15, GM-CSF, MIP-1b, RANTES, VEGF were elevated. Conclusion These observations point to the possibility of determining specific cytokine/chemokine patterns associated with various diseases. Finally, although it may be said that the assay variations in beads-based multiplex assays tend to be broad, we believe they are still a very useful tool to characterize the pattern of cytokines/chemokines levels in various diseases.

A DNA polymerase with properties similar to mammalian polymerase delta has been isolated to near homogeneity from early embryos of Drosophila melanogaster. A combination of exclusion chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis indicates that this enzyme has a total molecular mass of 185 kDa and is composed of 138- and 47-kDa polypeptides. Its isoelectric point is 6.8. This polymerase activity is strongly inhibited by N-ethylmaleimide, aphidicolin, and high KCl concentration but is relatively insensitive to 2',3'-dideoxythymidine 5'-triphosphate. There was no reaction in an immunological test using monoclonal antibody against Drosophila DNA polymerase alpha. In a final purification step, this polymerase activity was accompanied by 3'--5'-exonuclease activity as expected proof-reading activity. This polymerase activity is remarkably stimulated by mouse proliferating cell nuclear antigen, which is structurally and immunologically very similar to a Drosophila counterpart. These properties clearly indicate this enzyme belongs to the category of DNA polymerase delta.

We report a rare case of spontaneous rupture of the ascending aorta without any evidence of aneurysm formation or aortic dissection. A woman aged 64 was admitted to our cardiac care unit as an emergency patient with severe chest pain. Her face was pale and systolic blood pressure was 70 mmHg in spite of intravenous administration of dopamine (10 micrograms/kg/min). She had a history of hypertension for two years under good medical control. No trace of the chest trauma was noted before her admission. Physical examination revealed neck vein engorgement and distant heart sounds. Chest X-ray film showed enlargement of the cardiac silhouette. ECG showed no evidence of acute coronary syndrome. Pericardial effusion with a floating hematoma-like mass was detected by 2-dimensional echocardiogram. Pericardiocentesis revealed bloody pericardial fluid (Ht: 26%). Aortagraphy was performed resulting in a clinical diagnosis of acute aortic dissection, but there were no signs of a false lumen, aneurysm formation or extravasation of the contrast medium. Although continuous pericardial drainage was performed, she suddenly lost consciousness, collapsed and died. A longitudinal intimal laceration 5 cm long was observed in the ascending aorta. Pathological examination revealed cystic medial necrosis and irregularity of the elastic fibers in the media. No atheromatous plaque was noted in the intima. Spontaneous rupture of the aorta is a life-threatening condition that requires urgent surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

We analyzed 70 patients (64 from the literature and 6 of our own cases) who had suffered from rerupture of their aneurysms during angiography. When these cases are compared with those who had suffered rupture of their aneurysms only once and a rerupture, which did not coincide with angiography, they were clinically distinguished by a higher Hunt-Hess grade, a higher rate of IC aneurysms, less operability, far miserable outcome and concentration of aneurysmal rerupture within three hours after the initial subarachnoid haemorrhage. It is suggested waiting at least 3 hours after SAH before performing angiography and to use digital subtraction angiography in order to prevent aneurysmal rerupture during angiography.

Experience with Radio Isotope Myelography is reported here. 169Yb-DTPA as a tracer was intrathecally injected at lumbar region in twenty three patients with various spinal cord lesions. The first scanning is perfomed after comfirming by gamma-camera that the tracer reaches to the lesion, the second and the third scannings are done according to the ascending rate of the tracer. (I) Normal scintimyelogram (A) In normal case, the shape of the Radio Isotope Myelogram well corresponds the shape of anatomical subarachnoid space. (B) In normal adult cases, the tracer comes up to the cisterna magna in 20-25 minutes after the lumbar injection. Therefore, the scintimyelographic diagnosis should be made not only by the shape but also by the ascending rapidity of the tracer. (II) Abnormal scintimyelogram Abnormal scintimyelograms could be summarized as following three categories. (A) "Delay": It means delay of the ascending of the tracer. Besides, "Transient delay" found in a case of Arnord-Chiari's malformation was proposed. (B) "Partial block": It meas a defect at the level of the lesion. This "Partial block" were observed in cases of spinal cord angioma, cervical spondylosis and spinal cord tumor etc. (C) "Complete block": It means the stagnation of the tracer below the lesion. To sum up, Rario Isotope Myelography, especially in partial block, can more easily and more sensitively represent the maximum extent of the spinal cord lesion than other myelographic study or angiographic one. On the other hand, we can not qualitatively diagnose about the lesions by its indistinct border.

Spinal intradural arachnoid cysts (S-IAC) are rarely found and only 80 cases have been reported since 1915. We report two of them. A 68-year-old male had slowly progressive dull pain in both thighs for about 6 years prior to admission. Neurological examination and plain x-ray on admission showed no abnormality. Myodil myelography showed a S-IAC at T4 vertebral level. Surgical treatment of cyst wall excision resulted in success. The other case, a 39-year-old male suddenly noticed monoparesis and sensory disturbance of left leg in the morning. On admission were observed spastic monoparesis of the left leg, analgesia at right T2-3 cord segment and sensory disturbance (hypesthesia, dysesthesia, paresthesia) below T3-4 cord segment on the left side. Plain X-ray showed no abnormality. Myodil myelography revealed a S-IAC at T3-4 vertebral level. This patient was treated not surgically but conservatively because all neurological deficits but numbness in the left leg almost subsided after bed rest. The patient has experienced no neurological deterioration for five years since then. We also discuss the clinical feature, treatment and etiology of the S-IAC, by analyzing these 82 cases. There is a slight male preponderance. The age ranges between 3 and 66 years (mean 38 years). The duration from onset to admission is 2 days to 30 years. Sixty percent (48/80) of the cases were ill far longer than a year (mean 6.7 years). Of 82 cases, 83% suffered from motor disturbance, 70% had sensery disturbance, 62% local pain and 24% urinary with/without fecal disturbance.(ABSTRACT TRUNCATED AT 250 WORDS)

The correlation between the dissolution rate and bioavailability in humans for five indomethacin capsules was investigated. The mean Cmax, Tmax and AUC24 of low gastric acidity in humans correlated well with the dissolution rate determined by the paddle method using a slow stirring rate. The Cmax of the high acidity subjects also correlated with the dissolution rates determined under mild conditions. However, the Tmax correlated with the dissolution rates determined under vigorous ones. The in vivo-in vitro correlation seems to have become complicated by an anomalous product whose dissolution was remarkably sensitive to environmental conditions. The correlation data also suggested that the deaggregation force on the adhesive agglomerate in human digestive tract might not be strong.

The healthy male volunteers participating in bioavailability tests of diazepam tablets were classified into two groups, high and low acidity groups, on the basis of the acidity of their gastric fluid. This was estimated by the Gastrotest method. The bioavailability parameters of four tablet preparations of diazepam (5 mg) after single administration were compared statistically between the two groups. Subjects with low acidity showed significantly lower diazepam serum levels than subjects with high acidity at 1 and/or 2 h after administration of tablets B, C, and D, which showed slower rates of dissolution at pH 4.6. Tablet B gave a significantly lower peak concentration than the other tablets in the high acidity group, whereas in the low acidity group tablet A gave a higher level than the other tablets. The peak concentration in the low acidity group correlated well with the dissolution rates represented as 1/T70 (time of 70% dissolution) at pH 4.6, but we could not find a good method for determining the dissolution rates except for T50 values with the rotating flask method at pH 4.6; these values significantly correlated with the peak concentrations of the high acidity group. From our results we conclude that the acidity of the gastric fluid affects the bioavailability of a drug such as diazepam, which has a pH-dependent dissolution rate and an especially slow rate of dissolution at pH 3-7.

We reviewed 40 cases of intracranial ruptured aneurysm with intracerebral hematoma (An-ICH) and compared those with 177 cases of intracranial single ruptured aneurysm causing only subarachnoid hemorrhage (An-SAH). An-ICH accounted 11.6% of the intracranial aneurysm, ruptured at the mean age of 54 years, and occurred equally in both sexes. The localization of An-ICH was 50% in the middle cerebral artery (MC), 43% in the anterior cerebral artery (AC) and 8% in the internal carotid arterial region. Forty percent of An-ICH were treated conservatively and the outcome was very misery (no useful life and 94% was poor or dead). Sixty percent of An-ICH were treated surgically (neck-clipping and removal of the hematoma) and the outcome was poor (17% useful life and 46% poor and dead). Especially in MC aneurysm, operability was 85% and post-operative useful life was 12% and post-operative poor or dead was 53%. In AC aneurysm, operability was 35% and post-operative useful life was 33% and poor or dead was 33%. These miserable results raised a question of operative indication for An-ICH. The five clinical indices (decerebration, hypertension greater than or equal to 200 mmHg, Hunt-Hess grade V, anisocoria in AC, severe shift of midline structure on X-CT) were selected, because any patients who presented with even only one of them became fatal or vegetative state regardless of conservative or surgical treatment. Assuming them as the non-operative standards, operability decreased in 35% MC, 29% AC, useful life outcome came up to 20% MC, 40% AC, and misery outcome came down to 20% MC, 20% AC.(ABSTRACT TRUNCATED AT 250 WORDS)

It is important to have information about physical property of the brain in order to elucidate both the physical changes of the morbid brain and the physical mechanism of the traumatic brain injury. Under the hypothesis that reaction of the active brain to the dynamic load can be compared to the Maxwell-Voigt three dimensional model, elastic property of the brain was obtained as the Young's modulus (E: 10(-2) Kgf/cm2) of which error was less than 10%, and viscous property of the brain as the Viscous modulus (eta: 10(-2) Kgf.sec/cm2). And it was confirmed that the reactive pressure of the brain to dynamic load came from the surface to about 15 mm depth of the brain. In this report, experiments were done on the alive normal brains, the edematous ones nd necrotic ones which were produced by the cold injury (dry ice-aceton) in dogs (9.0--16.0 Kg). In the normal brain, E = 3.24 +/- 0.25, eta = 1.10 +/- 0.37 and these moduli were also stable when the physical conditions of the brain were stable. Under the dehydration by 20% mannitol, E increased in its value (p less than 0.01). But under the hydration by 5% glucose, E did not change at all. In the edematous brain, E = 3.28 +/- 0.44, eta = 1.74 +/- 0.06 and E of the edematous brain was almost same as that of normal ones, but under the dehydration, E of the edematous brain decreased (p less than 0.10), on the other hand it increased in its value under the hydration (p less than 0.05). In the necrotic brain, E = 1.60 +/- 0.14, eta = 0.82 +/- 0.28. Both moduli were of lower values and moreover they did not change its values at all under dehydration and hydration. As Young's modulus is the elastic index of the brain, the converse (1/E) should be compliance of the brain, that is to say, buffer effect of the brain. As for the compliance, the necrotic brain has maximum buffer effect and the over-hydrated edematous brain and the dehydrated normal ones have minimum buffer effect. From analysing the changes of the viscous moduli, it became clear that the viscous moduli took quite different functions in alive brains and in fatal ones, and it was suspected that the alive brain might not be so simple in its viscoelastic property.

The bioavailabilities of five indomethacin capsules were studied in ten beagle dogs and correlations with the in vivo results in humans and dissolution rates were investigated. The difference in bioavailability between two commercial products was smaller in dogs than in humans, which seemed to be due to strong disintegration forces in dogs. The difference in the dissolution rate among the products was reflected less in the Tmax in dogs than in humans, and the Tmax was shorter in dogs which seems to be due to faster gastric emptying and passage of the drug through the absorption site in dogs. Gastric acidity effects on the indomethacin availability found in humans were not observed in dogs. The Cmax and Tmax correlated well with the in vitro dissolution rates, but AUC24 did not. The Cmax and Tmax in dogs also correlated with the corresponding parameters in humans, especially those in high gastric acidity humans, but AUC24 did not.

Bioavailabilities of three commercially available tablets and two trial tablets of nalidixic acid were determined. The correlation between in vivo bioavailability parameters and in vitro dissolution rates derived by eight methods (oscillating basket I and II, beaker I, II, and III, rotating basket, paddle and rotating flask) is discussed. Nalidixic acid and its metabolite, 7-hydroxynalidixic acid, were determined in serum by HPLC with a strong anion-exchange resin column. All parameters for nalidixic acid bioavailability showed significant differences among the tablets tested. The relationship between Cmax and AUC was not linear but concave. However, Cmax decreased linearly in proportion to the delay of Tmax. The rank order of tablets according to bioavailabilities was just the same as the rank order obtained when comparing dissolution rates determined by any of the above methods, with the exception of one tablet which had a poor disintegrating ability. The parameters for the rate of bioavailability (Cmax and Tmax) showed good linearity with 1/T50 determined by all of the methods. However, AUC showed significant correlation with neither T50 nor 1/T50.