Effects of anthocyanidin derivative (HK-008) on relaxation in rat perfused mesenterial bed.

Anthocyanins, which are responsible for a variety of bright colors (including red, blue, and purple) in fruits, vegetables, and flowers, are consumed as dietary polyphenols. Anthocyanin-containing fruits are thought to decrease coronary heart disease and are used in anti-diabetic preparations. Diabetes is associated with a variety of cardiovascular complications that may be mediated by endothelial dysfunction, and so this study was designed mainly to characterize the influence of a synthesized anthocyanidin derivative (HK-008) over acetylcholine (ACh)-induced relaxation in mesenteric arterial beds isolated from rats. In a glucose-tolerance test in intact rats, HK-008 (30 mg/kg) reduced the glucose level as effectively as the same dose of glibenclamide. The aortic relaxation induced by pinacidil (an ATP-sensitive potassium channel opener) was greatly inhibited by glibenclamide (10 microM), and also significantly inhibited by HK-008 (10 microM). Interestingly, the ACh-induced relaxation in the perfused, preconstricted mesenteric arterial bed was significantly enhanced by HK-008 (10 microM), and this enhancement was significantly attenuated by indomethacin (10 microM). The ACh-induced mesenteric relaxation was impaired by an increase in oxidative stress, viz. superoxide-generating treatment [xanthine oxidase (XO; 0.1 U/ml) plus hypoxanthine (HX; 10 microM)]. However, this impairment was strongly suppressed by HK-008 (10 microM). These results suggest that HK-008 increases endothelium-induced relaxation by suppressing oxidative stress or modulating prostanoids signaling. This compound may therefore be useful against certain cardiovascular disorders.     

Study of the localization of radiopacities similar to calcified carotid atheroma by means of panoramic radiography.

OBJECTIVE: To determine the location in soft tissues of the calcifications, similar to calcified carotid atheromas, that can be observed radiographically in the cervical region in panoramic radiographs. STUDY DESIGN: In each anatomic cadaver specimen preserved in formol, consisting of the head and neck, radiopaque spheres (made from gutta-percha) were positioned in anatomic structures of the cervical region that can be sites of calcification. For each anatomic structure marked in this way, panoramic radiography was performed, consisting of 17 radiographs. The images obtained were analyzed by 24 examiners who indicated which radiographs, in their opinion, presented the radiopaque reference projected in the region of bifurcation of the carotid artery. Analysis of 2 proportions from agreement and disagreement was used to determine radiopacities that could be confused in panoramic radiographs with calcified atheromas in the carotid artery. RESULTS: The results showed that 75% (18) of the examiners correctly indicated the reference in the bifurcation of the carotid artery and 79.2% (19) indicated a triticeous cartilage as calcified atheroma of the carotid artery. CONCLUSIONS: Calcified atheromas of the carotid artery are not the only features that can produce radiopaque images lateral to the panoramic radiograph; the presence of calcification in the triticeous cartilage also can induce an erroneous diagnosis of calcified carotid atheroma.     

Evaluating New and Traditional Methods for Aminoglycoside Dosing in Patients With Various Degrees of Renal Function

Aminoglycosides are widely used, and clinicians continue to seek newer and better methods for initial dosing of these agents. Recently, three new methods were introduced: Thomson, Reesor Nimmo, and dosing in Tenopathy by easy-to-use multipliers (DREM). In comparing them with older, traditional dosing methods in patients with various degrees of renal function, the pharmacokinetic variables of gentamicin were determined from steady-state peak (C_max) and trough (C_min) serum concentrations using individualized regimens in 88 patients. Dosages were determined in each patient using the method of Hull-Sarubbi, rule of eights, and the three new methods, and the resultant C_max and C_min values were calculated from dosages generated by each method. The daily doses and C_max values derived with the Hull-Sarubbi, Thomson, and Reesor Nimmo methods were not significantly different (p>0.05). The Hull-Sarubbi was the most precise (root mean squared prediction error 1.3) and least biased (mean prediction error −0.05) of the five methods in predicting target gentamicin serum peak concentrations (C_max 6.5 mg/L). The Hull-Sarubbi (69%), Thomson (86%), and Reesor Nimmo (70%) methods yielded therapeutic C_max (5–8 mg/L) in a significantly higher percentage of patients than did the rule of eights (32%) and DREM (35%), (p<0.05). Therefore, if gentamicin serum concentrations are not available, the first three appear to be reasonable methods for initiating gentamicin dosage regimens, but the last two may not be desirable to use in a clinical setting. These conclusions are based on the assumption that patients are adults with stable renal function and relatively stable clinical conditions.     

Identification of antibacterial principles against Streptococcus mutans and inhibitory principles against glucosyltransferase from the seed of Areca catechu L

During the course of our studies on dental caries prevention by traditional medicines, fatty acids (myristic and oleic acids etc.) and procyanidins from betel nuts (the seed of Areca catechu L.) were respectively revealed to be the major antibacterial principles against a primary cariogenic bacterium, Streptococcus mutans, and the major inhibitory principles against glucosyltransferase from S. mutans.     

Intravesical combination chemotherapy with mitomycin C and doxorubicin for superficial bladder cancer: a randomized trial of maintenance versus no maintenance following a complete response

Between November 1986 and April 1989, 101 patients with superficial bladder cancer were treated with intravesical instillations of mitomycin C on day 1 and doxorubicin on day 2 of each week for 5 consecutive weeks. Of 61 complete responders, 23 patients with carcinoma in situ and 28 with papillary cancer were randomly assigned to a non-maintenance group or to a group receiving maintenance therapy consisting of monthly instillations of the same drugs for 12 months. The 2-year non-recurrence rate calculated for patients with carcinoma in situ was significantly better in the maintenance group than in the non-maintenance group. A similar tendency was observed for patients with papillary cancer, although the difference was not significant. Side effects were considerable, with moderate to severe bladder irritation occurring in approximately half of the patients. In addition to our previous findings, the present results indicate that this intravesical combination chemotherapy is effective in eliminating superficial bladder cancers and that since the effect is not durable, even in complete responders, maintenance therapy is necessary to reduce subsequent tumor recurrence.Presented at the 4th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 16–17 November 1990, Osaka, Japan     

Different antigenic nature in apparently healthy women with high serum CA 125 levels compared with typical patients with ovarian cancer.

BACKGROUND. CA 125 is a representative ovarian cancer-associated antigen defined by monoclonal antibody OC125. Recently, monoclonal antibodies were produced (designated 130-22 and 145-9) that were reactive with CA 125 but bound to a separate epitope named CA 130. There was a close correlation between serum CA 125 and CA 130 values in most instances. However, among more than 8000 serum samples, 5 apparently normal women had high serum CA 125 values, despite having normal CA 130 values. In this study, the antigenic nature of these five women was investigated. METHODS. Using gel chromatography, the molecular masses of CA 125 and CA 130 were estimated that were found in the five women with false-positive CA 125 values. The sera were examined using double-determinant assays combining iodine-125-labeled OC125 or iodine-125-labeled 130-22 with OCI25-coated or 145-9-coated beads. RESULTS. The molecular masses of both CA 125 and CA 130 were estimated as greater than 1000 kilodaltons (KD); the CA 130 mass from one of the five women with an abnormal CA 125 level was approximately 200 KD using gel chromatography. Using the double-determinant assays that combined iodine-125-labeled OC125 or iodine-125-labeled 130-22 with OC125-coated or 145-9-coated beads, high radioactivity was found only in the homologous assay using iodine-125-labeled OC125 with OC125-coated beads. These results suggest that the antigenic nature of CA 125 found in apparently healthy women differs from that found in patients with ovarian cancer and that CA 130 epitopes are not present. CONCLUSIONS. Measurement of serum CA 130 concentrations may be useful for excluding women with falsely elevated CA 125 values.     

Guidance of dopaminergic neuritic growth by immature astrocytes in organotypic cultures of rat fetal ventral mesencephalon.

Astrocytes, with their many functions in producing and controlling the environment in the brain, are of great interest when it comes to studying regeneration after injury and neurodegenerative diseases such as in grafting in Parkinson's disease. This study was performed to investigate astrocytic guidance of growth derived from dopaminergic neurons using organotypic cultures of rat fetal ventral mesencephalon. Primary cultures were studied at different time points starting from 3 days up to 28 days. Cultures were treated with either interleukin-1 beta (IL-1 beta), which has stimulating effects on astrocytic proliferation, or the astrocytic inhibitor cytosine arabinoside (Ara-C). Tyrosine hydroxylase (TH)-immunohistochemistry was used to visualize dopaminergic neurons, and antibodies against glial fibrillary acidic protein (GFAP) and S100 beta were used to label astrocytes. The results revealed that a robust TH-positive nerve fiber production was seen already at 3 days in vitro. These neurites had disappeared by 5 days. This early nerve fiber outgrowth was not guided by direct interactions with glial cells. Later, at 7 days in vitro, a second wave of TH-positive neuritic outgrowth was clearly observed. GFAP-positive astrocytic processes guided these neurites. TH-positive neurites arborized overlying S100 beta-positive astrocytes in an area distal to the GFAP-positive astrocytic processes. Treatment with IL-1 beta resulted in an increased area of TH-positive nerve fiber network. In cultures treated with Ara-C, neither astrocytes nor outgrowth of dopaminergic neurites were observed. In conclusion, this study shows that astrocytes play a major role in long-term dopaminergic outgrowth, both in axonal elongation and branching of neurites. The long-term nerve fiber growth is preceded by an early transient outgrowth of dopamine neurites.     

Time-course changes of regional cerebral blood flow by SPECT with N-isopropyl-p-[123I]-iodoamphetamine in childhood partial seizures]

Single photon emission computed tomography (SPECT) with N-isopropyl-p-[123I]-iodoamphetamine was performed twice at different times in 18 children suffering from partial seizures to evaluate the time-course changes of the hemodynamics in the focal region. Comparison of the 2 SPECT images revealed that a decreased regional cerebral blood flow (CBF) in the first was normalized in 4 cases (22.2%) and contracted in 7 cases (38.9%). The region of decreased blood flow in the second was contralateral to that in the first in 1 case (5.6%) and unchanged in 6 cases (33.3%). Most of the normalized and contracted cases were those in which clinical seizures disappeared and the EEG findings were normalized. In these cases which responded to treatment, the decreased regional CBF was also found to be improved. Repeated SPECT appears to be useful for evaluating the therapeutic efficacy. On the other hand, most of the unchanged cases were those in which clinical seizures were frequent or uncontrolled, or which persistently showed the abnormalities in their EEG. SPECT was considered to reflect well the conditions of the epileptic foci. These results indicate that repeated SPECT for observing the time-course changes of the regional CBF represents a useful technique with can be applied in evaluating the therapeutic efficacy or deciding the time to discontinue treatment and for pathogenetic elucidation of the epileptic foci.     

Electrogastrographic activity in patients who received proximal gastrectomy plus jejunal interposition or total gastrectomy plus jejunal interposition.

Electrogastrograms (EGGs) were recorded in patients both before and after receiving proximal gastrectomy plus jejunal interposition (PGJI) or just after receiving total gastrectomy plus jejunal interposition (TGJI). Intraluminal pressure was also recorded in some postoperative patients. The EGG 3 cpm component (2.5-4.9 cpm) remained after PGJI, but subsequently decreased with a significant reduction in the preoperative to postoperative ratio of the 3 cpm components (P<0.05). The mean frequency of the 3 cpm components increased significantly after PGJI (P<0.05) and its instability factor increased. The EGG 10 cpm components became relatively dominant compared to other frequency components in 2 out of 8 of patients having PGJI but the mean amplitude of 10 cpm decreased. In TGJI patients, only the 10 cpm component was conspicuous in EGG as in the case of total gastrectomy and Roux en Y anastomosis procedures. The spectral frequencies of intraluminal pressure in the interposed jejunum were similar to the EGG of 10 cpm components both in the case of PGJI and TGJI patients. In conclusion, surface EGG could record the electrical activities of the interposed jejunum more easily in patients having had TGJI than in PGJI.