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Purpose: To examine the electroretinograms (ERGs) of the short-wavelength-sensitive (S-) and the mixed long- and middle-wavelength-sensitive (L,M-) cones, and the ON- and OFF-responses of the cone ERGs in three patients with X-linked juvenile retinoschisis (XLRS)., Methods: Cone ERGs elicited by different color flashes and those elicited by long duration stimuli under Ganzfeld conditions were recorded from three patients with XLRS., Results: The S-cone b-waves were undetectable to short-wavelength stimuli in all three XLRS patients, while the L,M-cone ERG b-waves were within the normal range. To long-duration white stimuli, the ON-response (b-wave) was reduced and delayed in all patients compared with that of the normal subjects, while the d-wave or OFF-response appeared normal in amplitude and implicit time., Conclusions: These results support the hypothesis that the normal S-cone ERG arises primarily from the ON-pathway of the cone ERGs and the hypothesis that ON-bipolar cells are predominant in the S-cone system.

The essential aim of this study was to compare two different methods, Southern hybridization and fluorescence polarization (FP) assay. They both detect specific hybridization and were examined using common asymmetric PCR products and probes. FP assay clearly showed the hybridization of probe DNAs with the asymmetric PCR products of their target genes. Southern blot patterns presented excellent consistency with the results of FP assay. In both methods, two types of Shiga toxin (vero toxin) genes held in enterohaemorrhagic Escherichia coli (EHEC) were used as target genes. For detection of the two genes, stx1 and stx2, two respective DNA probes were synthesized. Both in FP assay and in Southern hybridization, the probe for stx1 hybridized only with the product of stx1 and vice versa. The results of the DNA detection using different methods were completely in agreement. Moreover, FP assay makes it possible to detect the hybridization rapidly. In our high NaCl concentration condition, hybridization between the probes and the asymmetric PCR products could be monitored within about 15min.

Procarbazine, a drug used for cancer chemotherapy, is carcinogenic in rodent bioassays. We analyzed the mutagenicity of procarbazine in various organs and the clastogenicity of the drug in hematopoietic cells of the lacZ transgenic MutaMouse. This was part of the second collaborative study of the Mammalian Mutagenesis Study Group of the Japanese Environmental Mutagen Society on the transgenic mouse mutation assay. At 50 mg kg(-1), procarbazine induced micronuclei in hematopoietic cells, but it did not increase the lacZ mutant frequency (MF) in bone marrow. It was also negative in liver, testis, spleen, kidney, and lung. Five daily administrations of 150 mg kg(-1) yielded highly positive responses in the drug's target organs for carcinogenesis (lung, bone marrow, and spleen). Lower positive responses were detected in kidney, which is a minor target organ. Liver showed only a slight increase in lacZ MF and brain showed no increase. The testis MF more than doubled which suggest that procarbazine is mutagenic to germ cells. Thus, we demonstrated that procarbazine has a strong clastogenic effect in hematopoietic cells and is mutagenic in a variety organs after high dose treatment. The induced MF was especially high in procarbazine's target organs for carcinogenesis, which supports the relevance of the transgenic mouse mutation assay for the assessment of potential genotoxins in vivo.

We compared the noradrenaline (NA) level in the dorsal horn following electrical stimulation of A delta afferent nerve fibers in the peripheral nervous system between rats with bilateral lesions of the locus coeruleus (LC) and non-operated control rats by using a microdialysis technique combined with high performance liquid chromatography. Prior to A delta afferent fiber stimulation, the NA content in the dialysate did not differ between the LC-lesioned and the control rats. During A delta afferent fiber stimulation, in the LC-lesioned rats, the NA level did not change significantly compared to that before A delta afferent fiber stimulation, whereas the NA level increased significantly in the control rats. There was a significant difference in the NA levels during A delta afferent fiber stimulation between the two groups of rats. The result suggests that descending noradrenergic neurons from the LC is involved in the increase of the NA level in the spinal cord dorsal horn produced by A delta afferent fiber stimulation.

We retrospectively studied surgical outcomes in 13 patients (13 eyes) who underwent vitrectomy for proliferative vitreoretinopathy (PVR) due to macular hole. While the success rate of the initial surgery was only 46% (6 eyes), retinal reattachment was ultimately obtained in 92% (12 eyes) with additional surgery. Reattachment rate in the initial was poor in eyes with posterior staphyloma. It was better in eyes treated with macular buckling and/or scleral encircling, and in eyes without iatrogenic retinal tears. These results indicate that appropriate treatment for the macular hole as well as extensive removal of vitreous gel and vitreoretinal traction are necessary in order to obtain the successful results in vitrectomy for PVR due to macular hole.

Several lines of evidence indicate that N-methyl-D-aspartate (NMDA) receptors play an important role in nociception in general and in pathological pain in particular. It has been previously demonstrated in behavioral studies that NMDA receptor antagonists attenuate pathological pain in humans and nociceptive behaviors in animals. In the present study, we investigated the effect of the NMDA receptor antagonist memantine (MEM) on the responses of spinothalamic tract (STT) cells in normal and neuropathic monkeys. Memantine was delivered into the spinal cord through a microdialysis fiber acutely implanted into the dorsal horn. Responses of STT cells to peripheral stimulation within their receptive fields were recorded before and after MEM infusion. In normal animals (n = 7), 10 mm MEM did not affect STT cell (n = 7) baseline activity or responses to mechanical stimuli (brush, press or pinch). In neuropathic animals (n = 6), 1.0, 3.0, 10.0 and 100 mm MEM did not affect baseline activity of STT cells (n = 7); however, in a dose-dependent fashion, it significantly reduced responses of these cells to all cutaneous stimuli. The data suggest that MEM can have a direct effect on STT cells, blocking NMDA receptors known to be present on this cell population and, furthermore, may be a therapeutic agent for chronic pain.

The effects of NaCl concentration, temperature and base-pair mismatches on the hybridization of two complementary single-stranded DNA 24-mers were investigated using a fluorescence polarization method. Over a temperature range of 46 degrees C to 56 degrees C in 0.8 M NaCl it was found that hybridization was essentially complete in under 10 minutes and that rapid in vitro determination of the target DNA was possible when the sample DNA had three or less base-pair mismatches in the 24-mer sequence. Polarization measurements on positive and negative samples showed excellent agreement with results obtained from electrophoresis. Under our optimized conditions, a 23 base-pair single-stranded DNA sequence of the Verotoxin gene (VT2) of Escherichia coli, previously multiplied using PCR (40 cycles), could be detected within 10 minutes.

Purpose: The purpose of this study was to investigate the binding mechanism of loop diuretics with HSA and to characterize the binding site on HSA., Methods: Quantitative analysis of potential interaction between ligands bound to HSA was performed by equilibrium dialysis and data for binding of the two ligands to HSA were analyzed on the basis of a theoretical model of simultaneous binding of two ligands., Results: The binding of loop diuretics is dependent upon the N-B transition, conformational change of albumin. Furthermore, from the results of binding of the drugs to modified HSA, the lysine residue seems to be involved in the binding of loop diuretics to HSA., Conclusions: Analysis using models describing independent, competitive, cooperative and anti-cooperative binding led to the conclusion that loop diuretics bind to site I, particularly to the warfarin region on HSA.

Activated eosinophils in airway epithelium are involved in the pathogenesis of many airway diseases. We examined whether activated eosinophils influence the secretion of phosphatidylcholine (PC), the predominant component of pulmonary surfactant, in primary culture of rat type II pneumocytes. The eosinophils (10(5) cells/ml) activated by opsonized zymosan (100 micrograms/ml) increased PC secretion from the type II pneumocytes. The increased PC secretion reduced in the presence of both superoxide dismutase (2 units/ml) and catalase (1000 units/ml). These results suggest that activated eosinophils stimulate the secretion of pulmonary surfactant partly through superoxide anions.

The protective effects of N-benzyl-D-glucamine dithiocarbamate (BGD) against the renal toxicity caused by repeated injections of cis-diamminedichloroplatinum (DDP) were studied in rats. The rats were injected i.p. with BGD (2.0 mmol/kg) immediately after i.v. injection of DDP (20 mumol/kg), and after 10 and 20 days they received repeated treatments with the same doses of DDP and BGD. Treatment with BGD prevented nephrotoxicity after repeated DDP administrations. Repeated DDP injections increased lipid peroxidation in the kidney and decreased GSH concentration in the kidney at 5 days after the third injection of DDP. BGD treatment prevented the increase in lipid peroxidation and the decrease in the GSH concentration caused by repeated administration of DDP. The determination of activities of antioxidant enzymes in the kidney showed that catalase activity decreased after repeated DDP administrations and that superoxide dismutase activity tended to decrease. Changes in activities of these enzymes were prevented by BGD treatment. The platinum concentrations in kidney and liver were decreased by BGD treatment. These results indicate that BGD treatment prevents the accumulation of platinum in the kidney after repeated administrations of DDP, resulting in protection against the DDP-induced renal toxicity.

Sodium diethyldithiocarbamate (DDTC) and sodium N-benzyl-D-glucamine dithiocarbamate (BGD) were compared for their protective effects against cis-diamminedichloroplatinum (DDP)-induced toxicity in kidney and gastrointestinal tract in rats. Rats were injected i.p. with the dithiocarbamates (2.0 mmol kg-1) immediately or 1 h after i.v. injection of DDP (20 mumol kg1). Treatment with BGD immediately or at 1 h after DDP injection effectively prevented the nephrotoxicity of DDP, but administration of DDTC immediately or 1 h after DDP afforded little protection. N-Benzyl-D-glucamine dithiocarbamte significantly reversed the reduction in maltase, sucrase and aminopeptidase activities of jejunal mucosa of rats treated with DDP, whereas treatment with DDTC concurrent with DDP could not reverse the reduction in disaccharidase activity following DDP injection. The platinum concentrations in liver and kidney were significantly decreased by treatment with BGD and DDTC. The treatment with DDTC at 1 h after DDP was more effective on the reduction of platinum concentrations in these tissues than that immediately after DDP. There was no difference between the renal and hepatic concentrations of platinum in two time intervals of BGD. The pharmacokinetic studies indicated that DDTC is more rapidly metabolized than BGD, resulting in larger total clearance and elimination rate constant values. These results reveal that the administration of BGD immediately and at 1 h after DDP can protect against the renal and gastrointestinal toxicities caused by DDP, whereas DDTC afforded little protection, and that the time interval between administration of DDP and DDTC greatly influences its protective effect on DDP-induced toxicity, indicating that the chelation therapy of BGD for DDP is superior to that of DDTC.

Xanthine derivatives, pentoxifylline, aminophylline, theophylline and chinoin-170, increased phosphatidylcholine secretion in a primary culture of rat type II pneumocytes. However, these xanthines alone had no effect on intracellular cAMP levels in type II pneumocytes. In contrast, terbutaline-induced secretion of phosphatidylcholine was augmented by these xanthines, and the augmentation depended on the increase of cAMP levels. These results suggest that the xanthines induce phosphatidylcholine secretion possibly through cAMP-dependent and cAMP-independent pathways in the primary culture of rat type II pneumocytes.

The author presents an improved method of preparation for colonoscopy that involved no dietary limitation on the patient until the day of the examination and that was shown by a randomized questionnaire evaluation to earn good patient tolerance and acceptance. Patients were given 10 mg of cisapride and 75 mg of sodium picosulfate before sleep on the day preceding the examination, and 50 g of magnesium citrate powder (MP) in 1,200 mL lukewarm water before the examination. It was divided into 600-mL portions and ingested slowly during two 30-minute periods. Ninety-five percent of patients classified the taste of a magnesium citrate powder laxative as palatable in the questionnaire given immediately after the procedure. Concerning the quantity, 79.4% replied that it was tolerable, 17.3% considered it somewhat excessive, and 3.3% replied that it was barely tolerable. No patient classified it as intolerable. Symptoms after taking laxatives and lukewarm water such as abdominal pain, nausea and abdominal fullness were observed in 3.8%, 4.4% and 5.6%, respectively, whereas there were no symptoms in 79% of patients. Body weight and serum K level showed a tendency to decrease, whereas the serum Mg level showed an increase before and after colonoscopy. The quality of colonic cleansing evaluated by colonoscopy was excellent, good, or fair in a total of 93.3%. No adverse effects were observed. It was concluded that this method is a clinically beneficial and well-tolerated preparation for colonic examinations.

The interaction of a series of benzothiadiazides with human serum albumin (HSA) was investigated by equilibrium dialysis (ED) and spectroscopic methods including circular dichroism (CD). The primary binding site of benzothiadiazides was designated site II, the diazepam site on the HSA molecule, as indicated by displacement experiments using different site-selective probes. Tyrosine and lysine amino acid residues were probably involved in the binding site of these compounds to HSA. Both electrostatic and hydrophobic interactions were found to play a role in the binding of these compounds to HSA. Among the compounds tested, chlorothiazide had the highest affinity (K1 = 5.5 x 10(4) M-1, K2 = 5.8 x 10(3) M-1). The primary binding affinity of the compounds for HSA was of the order: chlorothiazide > cyclopenthiazide > polythiazide > ethiazide > trichlormethiazide = methyclothiazde > hydrochlorothiazide. Binding was insensitive to the N-B transition of HSA. The binding site is proposed to consist of a cationic site on the surface of the HSA molecular with a hydrophobic crevice to accommodate the aromatic ring of the compounds. Positions 3 and 7 of the benzothiadiazide molecule is thought to affect the binding affinity to HSA.

Sodium diethyldithiocarbamate (DDTC), sodium N-benzyl-D-glucamine dithiocarbamate (BGD), sodium N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD), and sodium N-p-carboxybenzyl-D-glucamine dithiocarbamate (CBGD) were evaluated for efficacy as inhibitors of cis-diamminedichloroplatinum (DDP)-induced nephrotoxicity in a rat model. Treatments with 2.0 mmol/kg of BGD, HBGD, and CBGD immediately after DDP (20 mumol/kg) injection effectively prevented the nephrotoxic effects of DDP, but administration of DDTC immediately after DDP injection afforded a small protection. Concurrent treatment with 0.5 or 1.0 mmol/kg of HBGD, or 1.0 mmol/kg of CBGD could prevent DDP-induced renal damage. A significant decrease in weight loss was also observed in these dithiocarbamate-rescued rats. The platinum concentrations in liver and kidney were significantly decreased by BGD, HBGD, and CBGD treatments, respectively. The antitumor efficacy of DDP in the Walker 256 carcinoma-bearing rats was not affected by administration of HBGD (1.0 mmol/kg) or CBGD (1.0 mmol/kg). The results of this study indicated that the injection of HBGD or CBGD to rats treated with DDP can protect against DDP-induced nephrotoxicity more effectively than DDTC or BGD.

Sodium N-benzyl-D-glucamine dithiocarbamate (BGD) was evaluated for its efficacy as an inhibitor of cis-diamminedichloroplatinum (DDP)-induced nephrotoxicity in a rat model. Treatment with 2.0 mmol/kg of BGD immediately after DDP injection effectively prevented nephrotoxic effects of DDP, but administration of BGD -1 or 1 h after DDP afforded a small protection. Concurrent treatment with 0.5 mmol/kg of BGD could not prevent renal damage. The platinum concentrations in liver and kidney were significantly decreased by BGD treatment. The antitumor efficacy of DDP in the Walker 256 carcinoma-bearing rats was not affected by administration of BGD (2.0 mmol/kg).

Effects of A-delta afferent fiber stimulation on the response threshold in the tail flick reflex were examined in rats anesthetized with thiamylal sodium. In a statistical analysis, the suppressive effect on the skin temperature at the time of the tail flick (tail flick temperature) was represented as a percent of maximal possible effect (%MPE) expressing more clearly the degree of change of the tail flick temperature. A-delta afferent fiber stimulation produced a reduction of EMG activity of the tail muscle, but no changes of both the tail flick latency and the tail flick temperature were observed. The results of the present study and the previously reported modulation system in the spinal cord dorsal horn are discussed.

The use of an antibody immobilized on latex or silver colloid in fluorescence polarization immunoassay (FPI) is assessed. In FPI it is possible to detect antigens of high molecular weight because the molecular weight of the antibody is effectively increased. In the assay for rabbit immunoglobulin G a limit of detection lower by two orders of magnitude and an assay range wider by one order of magnitude can be obtained in comparison with conventional FPI. The detection limit is 10(-10) mol l-1 and the total assay time for one sample is 8 min. This assay combines a low detection limit with a short assay time.

The conserved KTG triad in the class C beta-lactamase from Citrobacter freundii GN346 was examined as to its function by means of site-directed mutagenesis. The following conversions were performed; Lys-315 to arginine, alanine or glutamic acid, Thr-316 to valine, and Gly-317 to alanine, proline or isoleucine. The resultant mutant enzymes revealed that a basic amino acid at position 315 and a small uncharged residue at position 317 are essential for the enzyme activity, but a hydroxyl group at residue 316 is not required for the enzymatic catalysis. The kinetic properties of the purified Arg-315 and Val-316 enzymes provided information on the function of these residues.

Of 107 neurons from the sacral and coccygeal levels of the spinal cord in anesthetized intact rats examined, 62 wide-dynamic-range (WDR) neurons that responded to noxious heating of the tail were recorded. On the basis of their inhibitory responses through A-beta or A-delta afferent fibers to noxious stimulation, these neurons were classified into one of the following three types: Type I--neurons inhibited only by A-beta afferent nerve impulses; Type II--neurons inhibited only by A-delta afferent nerve impulses; Type III--neurons inhibited by both. The present results are compared with previously reported behavioral results.

In rats anesthetized with thiamylal sodium, responses of spinal cord dorsal horn neurons to noxious skin heating of the tail were recorded by extracellular microelectrodes. Inhibition of these responses by innocuous mechanical stimulation (light brushing) of the ipsilateral forelimb was assessed. Short-lasting application (3 min, or less) of light brushing did not inhibit neuronal responses to noxious heating. Long-lasting application (5 min, or more) inhibited responses of these neurons to noxious stimulation. The results indicate that, in the anesthetized rat, remotely applied innocuous cutaneous stimuli can inhibit nociceptive responses of dorsal horn neurons, if applied for a sufficiently long time.

Sodium N-benzyl-D-glucamine dithiocarbamate (BGD), sodium N-p-methylbenzyl-D-glucamine dithiocarbamate (MBGD), and sodium N-p-isopropylbenzyl-D-glucamine dithiocarbamate (PBGD), which were recently synthesized, were evaluated for their efficacy in the distribution and excretion of cadmium in rats and mice exposed to cadmium. Rats and mice were injected i.p. with 109CdCl2 (1 mg Cd/kg and 2 microCi 109Cd/one animal) and 3 days later, they were treated with the dithiocarbamates (400 mumol/kg) every other day for 2 weeks. These dithiocarbamates were effective in removing cadmium from the body without increasing the cadmium content in the kidney. After treatment with BGD, MBGD, and PBGD, cadmium was excreted mainly in the feces and the effect of MBGD and PBGD on the fecal excretion of cadmium was much larger than that of BGD. The treatment with these dithiocarbamates did not cause the redistribution of cadmium to brain, testes, and heart in rats and mice. The treatment of mice with PBGD decreased the concentrations of essential metals in liver, kidney, and brain. The extent of acute toxicity of the dithiocarbamates in mice was in the order PBGD greater than MBGD greater than BGD.

The purpose of the present study was to investigate the quantitative relation between the stimulus intensity and the response magnitude of the tail flick reflex. The EMG of a tail muscle was recorded from the extensor caudae medialis (ECM) muscle in the side contralateral to heat stimulation, and the area of integrated EMG for 1 sec was measured as the magnitude of EMG activity. The minimum temperature to the onset of the EMG was 42.3 +/- 0.4 degrees C. The relation between the stimulus intensity and the magnitude of an integrated EMG followed a power function with an exponent of about 8.5. The magnitude of an integrated EMG was decreased by about 50% of the control by an intraperitoneal administration of morphine (0.5 mg/kg). These results suggest that tail flick reflex is closely related to painful sensation, and that EMG activity of the ECM muscle is applicable as an electrophysiological indicator to noxious stimulation of the tail and an expressible indicator of the magnitude of pain.

Clinically, the fitness test of a denture base employing white silicone has been widely used, and there are several methods for assessing the results. However, none of the conventional methods of assessment are completely objective or quantitative. For solving these problems, a new system has been developed for measuring the mean film thickness of white silicone based on image analyzing. There are several factors that affect the results of the fitness test of the denture base, such as the shape of the denture, the condition of the mucosa within denture bearing area, bite force and the state of occlusal contact. Then, using the new system, these factors were examined for clinical application of the mean film thickness of white silicone. The experiments are composed of three stages. In the first stage, the white silicone was pressurized between two of tablets involved in three types, with a pressurizer. These data resulted in a regression equation applying the rheological equation. In the second stage, pressurizing tests were performed on the models of jaw mucosa with uniform compressibility. The models were categorized into three types according to their compressibility. A result was the more compressible the models of jaw mucosa are, the thicker the white silicone film is. In the third stage, the compressibilities were mixed in the models of jaw mucosa. In the pressurizing test, the compressing dies were modeled on the denture base. Five loading points were established on the surface. Correlation between data obtained from the results of the pressurizing test at each loading point was investigated. The results from these experiments were as follows. 1. The regression equation was established from the compressing test of white silicone between tablets of rigid type. H = 0.236 (r1r2/square root of P) -0.0008 R = 0.977 H: mean film thickness of white silicone R: coefficient of correlation P: loading volume r1: 1/2 of the major side of the each tablet r2: 1/2 of the minor side of the each tablet Units are expressed in the C. G. S system. The film thickness was more highly correlated with the distance to the open system of each tablet than the area.

Recently it has been suggested that proto-oncogene plays a role not only in cellular proliferation, development and differentiation, but also in neoplastic transformation. We now show the expression and its localization of c-myc, c-fms and c-sis proto-oncogenes in human developing chorionic tissue and fresh surgical specimens of mole and choriocarcinoma with the method of Northern blotting and In-situ hybridization. The 2.4kb c-myc transcript has been localized to the cytotrophoblast in early placenta and also localized to the C and S typed trophoblastic cells in mole and choriocarcinoma. The 4.0kb c-fms transcript has been localized to the syncytiotrophoblast, especially the highly differentiated syncytiotrophoblast in the second and third trimesters and S typed trophoblastic cells in mole and choriocarcinoma. Moreover, the 4.0kb c-sis transcript has been localized to the cytotrophoblast in early placenta, but not detected in mole or choriocarcinoma. First, these results suggest that the stage and site specific expression of c-myc, c-fms and c-sis proto-oncogenes are clearly related to the proliferation, development and differentiation of normal trophoblastic cells. Second, the expression of c-myc, c-fms proto-oncogenes may be of particular importance in the tumorigenesis and progression of trophoblastic disease.

Electroacupuncture effects conveyed by A beta afferent nerve impulses from the different dermatomes, the Zusanli and the Hoku, was compared using the tail flick reflex in lightly anesthetized rats. The Zusanli stimulation decreased the EMG activity, but the threshold temperature did not change. These effects were not antagonized by naloxone (1 mg/kg). The Hoku stimulation also produced the suppression of the EMG activity without the increase of the threshold temperature. However, these effects were antagonized by naloxone (1 mg/kg). These results suggest that intrasegmental stimulation presynaptically inhibits the input of the noxious message in the spinal cord through the non-opiate system, while extrasegmental stimulation presynaptically inhibits this input through the opiate system.

The present study was to identify the physiological properties of the afferent fibers from the masseter muscle to the caudal part of the spinal trigeminal nucleus of rat using a microelectrode technique. When electrical stimulation was applied to the masseter muscle, the evoked potentials were recorded with a shorter latency (the S-response) or a longer latency (the L-response). The threshold current intensity of the S-response was lower than that of the L-response. There were statistical significant differences between the S-response and the L-response in latency and in threshold current intensity. Both the S- and L-responses could follow by stimulation of low frequencies (10 to 30 Hz), indicating that the evoked responses were the component of the secondary neuron activities. On the anatomical and physiological assumption, the conduction velocities of the S- and the L-responses were calculated and they were in the range of that of A-delta fibers. We also observed that both the S- and the L-responses could not follow high frequency stimulation of the masseter muscle. This effect may reflect the phenomenon of fatigue in the finely myelinated fibers or polymodal nociceptors. Thus, the present study suggested the involvement of the afferents from the masseter muscle to the spinal trigeminal nucleus in the transmission and the relay of the masticatory muscle pain.

Here is a report of three cases of delivery from women who have taken sodium valproate (VPA). One neonate was born with polydactylism, and we reviewed the congenital malformations in children of mothers who have taken VPA. In the other two cases, we also examined the levels of VPA in the cord serum and breast milk. The levels of VPA in the cord serum were 50 micrograms/ml at 12 hours after the last maternal dose and 75 micrograms/ml at 14 hours after the last maternal dose. The blood levels of VPA in the two mothers were 48-59 micrograms/ml and 55-85 micrograms/ml in their late pregnancy, respectively. The levels of VPA in the breast milk were 2.0-3.5 micrograms/ml and the ratio of VPA in the breast milk to blood was 2-3%. These results suggest the high rate of placental transfer and the low rate of milk transfer of VPA.

The effect of a single dose (50 mg/kg body weight) of 3-methylcholanthrene on de novo phosphatidylcholine biosynthetic activities in rat liver was studied both in a cell-free system and with slice experiments. 3-Methylcholanthrene caused a significant depression of either [methyl-14C]choline or [2-(3)H]glycerol incorporation into phosphatidylcholine when the precursor was incubated with liver slices. At the same time, there occurred a significant accumulation of radioactivity in either cholinephosphate or diacylglycerol molecule from [14C]choline or [3H]glycerol, respectively, suggesting that 3-methylcholanthrene could cause an inhibitory effect on hepatic phosphatidylcholine synthesis at the cholinephosphotransferase or/and cholinephosphate cytidylyltransferase step. Subsequent studies, where the activities of the three enzymes involved in de novo phosphatidylcholine synthesis were compared between control and 3-methylcholanthrene-pretreated rat liver subcellular fractions, demonstrated that the cholinephosphotransferase step could be the site of inhibition by 3-methylcholanthrene. On the other hand, 3-methylcholanthrene caused a significant induction of choline kinase activity in a time-dependent manner and, at the same time, the cholinephosphate pool size in liver cytosol was enlarged 2-3-fold when compared to the respective control. The overall results suggested strongly that 3-methylcholanthrene causes the counteractive effects on the de novo phosphatidylcholine biosynthesis, induction of choline kinase activity and inhibition of cholinephosphotransferase activity, both of which could participate in a concomitant increase in cholinephosphate pool size in rat liver.

Inclusion complexes of the digitalis glycosides digitoxin, digoxin, and methyl digoxin with three cyclodextrins (alpha-, beta-, gamma-homologues) in water and in the solid state were studied by a solubility method, IR and 1H-NMR spectroscopy, and X-ray diffractometry. Solid complexes (in a molar ratio of 1:4) of the digitalis glycosides with gamma-cyclodextrin were prepared and their in vivo absorption examined. The rapidly dissolving form of the gamma-cyclodextrin complex significantly increased plasma levels of digoxin (approximately 5.4-fold) after oral administration to dogs.

A new system is developed for measuring the mean film thickness of the white silicone on the fitness test of the denture base. This system is based on analysing the B/W film density replaced from the thickness of the silicone. The detective feature of this system is as follows: 1. An adequate correlation between the logarithm of the thickness of the white silicone and the logarithm of the B/W film density was estimated from the results of experimental values. 2. With use of the computer assembled into the system, it is capable to quickly process data. 3. Compared with the conventional method, the proper suggestion was gotten to the clinical data. 4. The system is available to use of investigating the bite force and the mean film thickness of the white silicone.

Inclusion complex of digoxin with gamma-cyclodextrin (gamma-CyD) in 1:4 molar ratio was prepared, and its dissolution and absorption behaviors were compared with those of digoxin alone. The dissolution rate of digoxin in water was found to be markedly increased by gamma-CyD complexation. Bioavailability of digoxin following the oral administration of gamma-CyD complex to dogs was 5.4 times as much as that of digoxin alone. The present data did indicate improvement of dissolution and absorption characteristics of digoxin by inclusion complexation, suggesting the decrease in dose in oral digoxin therapy.

1. The activities of choline kinase, ethanolamine kinase, cholinephosphate cytidylytransferase(s) and cholinephosphotransferase were compared in the liver subcellular fractions after the treatment of rats for two successive days with phenobarbital, 3-methylcholanthrene and polychlorinated biphenyls. 2. The administration of phenobarbital resulted in a significant decrease in choline kinase activity while not affecting ethanolamine kinase activity. Both 3-methylcholanthrene and polychlorinated biphenyls caused considerable enhancement of choline kinase activity concomitantly with ethanolamine kinase activity. 3. The activity of cytosolic cytidylytransferase was not affected by any of the inducers while the microsomal activity was significantly depressed by the administration of either phenobarbital or polychlorinated biphenyls. 4. The activity of microsomal cholinephosphotransferase decreased significantly after the treatment with both 3-methylcholanthrene and polychlorinated biphenyls and increased slightly after phenobarbital administration. 5. The observed opposite effects of phenobarbital and 3-methylcholanthrene on the enzymes in de novo phosphatidylcholine synthesis indicate that there exist a possible relation between induction of microsomal drug-metabolizing system and modulation of phosphatidylcholine biosynthesis in animal liver.

The dose limiting factors of cisplatinum are nephrotoxicity and emesis. Nephrotoxicity has been reduced by hydration but nausea and vomiting caused by cisplatinum have led to refusal of potentially curative therapy by a number of patients. The prevention of nausea and vomiting by a combination of antiemetic drugs administered to ovarian patients receiving chemotherapy inducing (cisplatinum 50mg/m2, adriamycin 300 mg/m2, cyclophosphamide 300 mg/m2 and 5FU 350 mg/m2) was studied. the combination antiemetic drugs were metoclopramide (1mg/kg), dexamethasone (10mg/m2), droperidol (1mg/m2) and diphenhydramine (20mg/body). These drugs without diphenhydramine were administered intravenously 30 minutes before and 2.5 hours, 5 hours and 7.5 hours after chemotherapy. Diphenhydramine was administered intramuscularly 30 minutes before and 5 hours after chemotherapy. No vomiting was noted in 82.6% (19/23) of cases, and no patient vomited more than four times. This combination regimen provided very good protection against cisplatinum induced emesis.