Effects of antidiabetes drugs on functional independence measure on a subacute rehabilitation ward for stroke patients.

It has been reported that the improvement of activities of daily living (ADL) by rehabilitation affects glycemic control. However, there are no reports about antidiabetes drugs as factors affecting the outcomes of rehabilitation. Therefore, we investigated the effects of antidiabetes drugs on functional independence measure (FIM) [total (T), motor (M), and cognition (C) items] in stroke patients with diabetes who were discharged from the subacute rehabilitation ward. We chose the frequently used antidiabetes drugs [sulfonylurea (SU), dipeptidyl peptidase-IV inhibitors (DPP-IVIs), and α-glycosidase inhibitors (α-GIs)] as the basis for categorizing the patients. We compared the patients' background features and laboratory data among the three groups. As a result, when SU was used in stroke patients with diabetes, it is difficult to obtain significant FIM-M gain, FIM-C gain, FIM-M efficiency, and FIM-C efficiency compared with of-GIs. As a reason for this, we hypothesize the possibility of the involvement of insulin resistance. Therefore, we consider that insulin resistance should be determined early and that it is important to reduce insulin resistance comprehensively by involving experts.

Analysis of factors for poor activated partial thromboplastin time control after dabigatran administration.

In this study, we compared patients whose activated partial thromboplastin time (APTT) was prolonged excessively with those whose APTT was controlled within the normal range after dabigatran administration. We analyzed the factors for the APTT prolongation. We divided the patients into two groups: those whose APTTs prolonged to more than 65 s and those whose APTTs were less than 65 s after dabigatran administration. There were 130 patients from March 2011 to July 2013, and we analyzed the background features and laboratory data of these patients. Results showed that there were no significant differences in the patients' background and laboratory data except for the high-density lipoprotein cholesterol (HDL-C) level. However, details of the relationship between the APTT prolongation and the HDL-C level are currently unknown. We hypothesize that the reason for the APTT prolongation is the variability in such parameters as the time of blood drawing, internal time of dabigatran, individual variability, and blood concentration. Therefore, we consider that these parameters need to be carefully evaluated even if APTT does not show prolongation.

Relativistic calculation of nuclear magnetic shielding using normalized elimination of the small component.

The normalized elimination of the small component (NESC) theory, recently proposed by Filatov and Cremer, is extended to include magnetic interactions and applied to the calculation of the nuclear magnetic shielding in HX (X=F, Cl, Br, I) systems. The NESC calculations are performed at the levels of the zeroth-order regular approximation (ZORA) and the second-order regular approximation (SORA). The calculations show that the NESC-ZORA results are very close to the NESC-SORA results, except for the shielding of the I nucleus. Both the NESC-ZORA and NESC-SORA calculations yield very similar results to the previously reported values obtained using the relativistic infinite-order two-component coupled Hartree-Fock method. The difference between NESC-ZORA and NESC-SORA results is significant for the shieldings of iodine.

Characterization of a newly found stretch-activated KCa,ATP channel in cultured chick ventricular myocytes.

With the use of the patch-clamp technique, five kinds of stretch-activated (SA) ion channels were identified on the basis of their single-channel conductances and ion selectivities in cultured chick ventricular myocytes. Because a high-conductance K+-selective channel predominated among these channels, we concentrated on characterizing its properties mostly using excised inside-out patches. With 145 mM KCl solution in the pipette and the bath, the channel had a conductance of 199.8 +/- 8.2 pS (n = 22). The ion selectivities among K+, Na+, Ca2+, and Cl- as estimated from their permeability ratios were PNa/PK = 0.03, PCa/PK = 0.025, and PCl/PK = 0.026. The probability of the channel being open (Po) increased with the Ca2+ concentration in the bath ([Ca2+]b; dissociation constant Kd = 0.51 microM at +30 mV) and membrane potential (voltage at half-maximal Po = 39.4 mV at 0.35 microM [Ca2+]b). The channel was blocked by gadolinium, tetraethylammonium, and charybdotoxin from the extracellular surface and, consequently, was identified as a Ca2+-activated K+ (KCa) channel type. The channel was also reversibly activated by ATP applied to the intracellular surface (Kd = 0.74 mM at 0.10 microM [Ca2+]b at +30 mV). From these data taken together, we concluded that the channel is a new type of KCa channel that could be designated as an "SA KCa,ATP channel." To our knowledge, this is the first report of KCa channel in heart cells.

Pharmacokinetics and polymorphic oxidation of dextromethorphan in a Japanese population.

The plasma concentration and cumulative urinary excretion over 34 h of dextromethorphan, free and conjugated dextrorphan, and 3-hydroxymorphinan were determined in seven healthy Japanese subjects after oral administration of 30 mg dextromethorphan hydrobromide. Conjugated metabolites were extensively present, whereas no detectable dextromethorphan or free metabolites were observed in the plasma of any subject. On average, 72% of the dose was excreted in urine within 34 h. This was detected mainly as conjugated metabolites with only slight traces of dextromethorphan and free metabolites. From the time-courses of the metabolic ratio (the ratio of urinary output of dextromethorphan to dextrorphan), the metabolic ratios seemed to become constant 7.5 h after oral administration. Phenotyping was performed using metabolic ratios in 75 unrelated healthy Japanese subjects (43 males and 32 females). The logarithmic metabolic ratio was bimodally distributed and one subject (1.3%) was identified as a poor metabolizer.

Andrastins A-C, new protein farnesyltransferase inhibitors produced by Penicillium sp. FO-3929. I. Producing strain, fermentation, isolation, and biological activities.

New protein farnesyltransferase inhibitors, andrastins A-C, have been discovered in the cultured broth of Penicillium sp. FO-3929. Andrastins extracted from broth supernatant were purified by silica gel chromatography, ODS chromatography and HPLC. The IC50 of andrastins A, B, and C against protein farnesyltransferase were 24.9, 47.1, and 13.3 microM, respectively.

Herquline B, a new platelet aggregation inhibitor produced by Penicillium herquei Fg-372.

A new herquline analog, herquline B was isolated from the culture broth of Penicillium herquei Fg372. Herquline B contains one piperazine and two cyclohexenones. The pyrrolidine ring of herquline A was cleaved to yield herquline B. The IC50 value of herquline B against platelet aggregation induced by ADP and platelet-activating factor were 1.6 and 5.0 microM, respectively.

Application of a novel, plastic formed carbon as a precolumn packing material for the liquid chromatographic determination of acetylcholine and choline in biological samples.

A novel carbon material, plastic formed carbon (PFC), was prepared by mixing various amounts of pure graphite with an organic binder and pyrolysing the mixture to a "glassy carbon" at a modest final temperature of 1000-1400 degrees C. This preparation procedure allows more convenient and precise control of the final graphite adsorption characteristics. Various PFC materials were constructed and tested both as bulk adsorbents and as precolumn packings for the direct determination of ACh and Ch in brain tissue homogenates. The PFC precolumns prepared from 12.5-50% graphite, by mass, were capable of selectively removing interfering species while not adsorbing any of the desired quaternary amine analytes. The usually large solvent front was also dramatically reduced with these precolumns. These PFC precolumns are useful for the direct determination of ACh and Ch in brain tissue homogenates and other biological samples.

Macrosphelide, a novel inhibitor of cell-cell adhesion molecule. I. Taxonomy, fermentation, isolation and biological activities.

Potent anti-adherent activity was detected in fermentation extracts of microbial strain FO-5050. Active compounds designated macrosphelide A and B were isolated and the structure was determined to be 16-membered macrolide antibiotics possessing three ester bonds in the ring structure. Macrosphelide A dose-dependently inhibited the adhesion of HL-60 cells to LPS-activated HUVEC monolayer (IC50, 3.5 microM); macrophelide B also inhibited HL-60 adhesion but to a lesser extent (IL50, 36 microM). Macrosphelide A did not show any antimicrobial and cytocidal activities at the concentration of 1000 micrograms/ml and 100 micrograms/ml, respectively.

Isochromophilones III-VI, inhibitors of acyl-CoA:cholesterol acyltransferase produced by Penicillium multicolor FO-3216.

New azaphilones named isochromophilones III-VI were isolated from the culture broth of Penicillium multicolor FO-3216 as inhibitors of acyl-CoA: cholesterol acyltransferase (ACAT). Their structures were elucidated by NMR and other spectroscopic analyses. The IC50 values of isochromophilones III, IV, V and VI for ACAT activity in an enzyme assay using rat liver microsomes were calculated to be 110, 50, 50 and 120 microM, respectively.

Prospective investigation of tumor markers and risk assessment in early cancer screening.

BACKGROUND: Many researchers have reported that tumor marker diagnosis may not be useful in the early detection of cancer. However, the authors proposed a new diagnostic system using a tumor marker combination assay. METHODS: The authors screened an asymptomatic population (2126 subjects) in Japan for early cancer over a 2-year period (1984-1986) using this tumor marker combination assay. The serum tumor marker combination assay data were analyzed: tumor-specific tumor markers (carcinoembryonic antigen, carbohydrate 19-9, heat-stable alkaline phosphatase, and tissue polypeptide antigen), tumor-associated tumor markers (ferritin, the ratio of ferritin to serum iron, immunosuppressive acidic protein, sialic acid), and growth-related tumor markers (alkaline phosphatase isoenzymes, ribonuclease). The tumor growth levels of the subjects were assessed by the tumor marker combination assay and classified into five tumor stages (Stage I, tumorfree; Stages II-III, precancer; Stage IV, preclinical cancer; Stage V, suggestive of cancer weighing over 1 g). The follow-up period was 5-7 years. RESULTS: The percentage of subjects in tumor stages IV and V increased with age, whereas the percentage in tumor stages II and III decreased. The distribution of screenees within each tumor stage was as follows: I, 0.1%; II, 11.8%; III, 58.8%; IV, 24.8%; V, 4.6%. The rate of incidence of cancer for Stages V, VI, III, II and I was 29.5% (28 of 95), 2.7% (14 of 528), 0.7% (9 of 1251), 0.4% (1 of 250), and 0 (0 of 2), respectively. CONCLUSIONS: Our tumor stage classification can adequately assess the risk of cancer developing in apparently healthy persons.

A short period oscillation in a water/oil/water system.

A new kind of potential oscillation with a short period of 7.5 s was found to occur in a water/oil/water system which consisted of an aqueous solution of surfactant, nitrobenzene and an aqueous solution of NaCI. A long period (approximately 10 min) oscillation previously reported was also found to be superposed on the new oscillation. The power spectrum of the short period oscillation has been measured.

Increase in carcinoembryonic antigen release from cancer cells by combined treatment with retinoic acid and low-temperature hyperthermia.

The growth of a human gastric adenocarcinoma cell line, MKN-45, was inhibited and the amount of carcinoembryonic antigen (CEA) in both the culture medium and the cell extract was increased in the presence of retinoic acid at a concentration of 75 (1.5x)-125 microM (1.9x), which did not substantially affect cell survival. Treatment using a combination of retinoic acid (125 microM) and low-temperature hyperthermia (40 degrees C, 30 min) was more effective in increasing CEA compared with retinoic acid alone (extracellular 1.9-2.4x, intracellular 1.5-1.9x). The inhibition of cell growth was reversed after the retinoic acid was removed from the medium. Cells treated with both retinoic acid and (low-temperature) hyperthermia, however, could be induced to release a significant amount of CEA at about 48 h after retinoic acid removal. The induced CEA increase in the cells, but not in the medium, was suppressed by actinomycin D (1 ng/ml) or cyclohexamide (0.2 microgram/ml). These results suggest that retinoic acid, used alone or in combination with hyperthermia, enhances the production and release of CEA in human gastric cancer cells.

Excitatory potential of artificial membrane in response to current pulse stimulation.

An excitatory potential generated in response to stimulation by a current pulse has been studied on an artificial membrane composed of a Nuclepore filter impregnated with sorbitan monooleate. An excitatory potential response accompanying a fall in the resistance of the membrane was found to occur above a threshold value of the pulse height for current stimulation. The relation between the pulse width of current stimulation and the threshold for the generation of an excitatory potential response has also been examined.

Oscillatory behavior of a water/oil interface system in response to current-clamp and voltage-clamp stimulation.

Oscillatory behavior in response to current-clamp and voltage-clamp stimulation was examined on a water/oil/water system consisting of an aqueous solution of sodium oleate as surfactant, a solution of 2,2'-bipyridine in nitrobenzene and an aqueous solution of sodium chloride. Stable oscillation was observed only when the strength of the stimulation lay within a specific range of values.

Critical change of ion conductance and self-sustained potential oscillation in artificial membrane systems.

A change in conductance of an artificial membrane at a threshold concentration of environmental salt solution was interpreted in terms of a change in adsorptive reaction rate on the interface which was derived from an autocatalytic reaction model. The model also accounted for a self-sustained potential oscillation which was observed when the salt concentration of one side of the membrane was higher than the threshold mentioned above and that of the other side lower.