Recent findings have indicated that insulin-like growth factors (IGF-I and IGF-II) may play a role in neoplasia. Alteration of serum IGFs or IGF Binding Proteins (IGFBPs) have been reported in some tumors. In this study, we measured serum IGF-I, IGF-II and IGFBPs profile in gastric cancer by radioimmunoassay and Western ligand blots. The serum IGF-I level in gastric cancer was significantly lower than in control subjects (65.2 +/- 26.5 vs 148.4 +/- 55.2 ng/ml, p < 0.01) and was further decreased to 45.5 +/- 20.9 ng/ml after surgery. The serum IGF-II level was slightly higher than that in control subjects (826.3 +/- 360.2 vs 735.7 +/- 154.6 ng/ml) but it was significantly decreased after surgery (525.7 +/- 220.1 ng/ml, p < 0.05). The serum IGFBP-3 level was not significantly different from those in control subjects. However, we observed a decreased level of serum IGFBP-3 after surgery, and incubation of postoperative serum with control serum resulted in a significant reduction of IGFBP-3 level. The reduction of IGFBP-3 in postoperative serum was mainly due to surgery associated IGFBP-3 protease activity. This protease activity was totally inhibited by aprotinin, EDTA and PMSF but not by pepstatin and leupeptin. This inhibition pattern is consistant with cation dependent serine protease. We speculate that proteolysis of IGFBP-3 may contribute to increase the bioavailability of IGFs.

Papaverine,[1][2][3]methyl]-6,-7-dimethoxyisoquinoline, has been used as a vasodilator agent and a therapeutic agent for cerebral vasospasm, renal colic, and penile impotence. We examined the effects of papaverine on a rapidly activating delayed rectifier K ϩ channel (hKv1.5) cloned from human heart and stably expressed in Ltk Ϫ cells as well as a corresponding K ϩ current (the ultrarapid delayed rectifier, I Kur ) in human atrial myocytes. Using the whole cell configuration of the patch-clamp technique, we found that papaverine inhibited hKv1.5 current in a time-and voltage-dependent manner with an IC 50 value of 43.4 M at ϩ60 mV. Papaverine accelerated the kinetics of the channel inactivation, suggesting the blockade of open channels. Papaverine (100 M) also blocked I Kur in human atrial myocytes. These results indicate that papaverine blocks hKv1.5 channels and native hKv1.5 channels in a concentration-, voltage-, state-, and time-dependent manner. This interaction suggests that papaverine could alter cardiac excitability in vivo.

KCB-328 [1-(2-amino-4-methanesulfonamidophenoxy)-2-[N-(3,4-dimethoxyphenethyl)-N-methylamino]ethane hydrochloride] is a newly synthesized class III antiarrhythmic drug and is known to be highly effective against various types of arrhythmias induced by coronary artery ligation, reperfusion, and programmed electrical stimulation. To understand the potential ionic mechanisms, we examined the effects of KCB-328, which encodes the rapidly activating delayed rectifier K ϩ current in cardiac tissues, on human ether-a-go-gorelated gene (HERG) channels expressed in Xenopus oocytes. The amplitudes of steady-state currents and tail currents of HERG were decreased by KCB-328 dose dependently. The decrease became more pronounced at more positive potential, suggesting that the block of HERG by KCB-328 is voltage-dependent. IC 50 values at Ϫ30, Ϫ20, Ϫ10, 0, ϩ10, ϩ20, ϩ30, and ϩ40 mV were 7.6 Ϯ 0.5, 4.8 Ϯ 0.4, 3.2 Ϯ 0.3, 2.1 Ϯ 0.3, 1.7 Ϯ 0.2, 1.4 Ϯ 0.2, 1.3 Ϯ 0.1, and 1.2 Ϯ 0.1 M, respectively. Induction of block depended on depolarization beyond the threshold for channel opening. In addition, time-dependent block developed slowly, with ϭ 1.7 Ϯ 0.3 s (100 M) at 0 mV, and was delayed by a stronger depolarization to ϩ80 mV, at which HERG channel is inactivated. We can conclude that KCB-328 preferentially blocks open (or activated) HERG channels. The block of HERG current might in part explain the underlying ionic mechanism for the antiarrhythmic and proarrhythmic effect of KCB-328.

We have previously demonstrated inhibition of basal Cl- secretion by intracellular bicarbonate concentration ([HCO3-]i) in rat distal colon. We now examined whether secretagogue-induced Cl- secretion is inhibited by [HCO3-]i as well. Stripped segments of distal colon from male Sprague-Dawley rats and the colon tumor cell line T84 were studied. Flux measurements were performed in the Ussing chamber under short-circuit conditions. [HCO3-]i was calculated from intracellular pH (pHi) values that were estimated with the pH-sensitive dye 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. Dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) and carbachol were used as secretagogues. In both distal colon and T84 cells, [HCO3-]i did not affect cAMP-induced Cl- secretion. However, carbachol-induced secretion was inhibited by [HCO3-]i; in rat colon, Cl- secretion decreased from 2.3 to 1.5 mueq.cm-2.h-1 when [HCO3-]i was increased from 15.0 to 28.4 mM (P < 0.05). In T84 cells, the change in short-circuit current decreased from 8.1 to 1.1 microA/cm2 over a range of [HCO3-]i from 0 to 15.6 mM (P < 0.001). We conclude that [HCO3-]i is an important modulator of carbachol-stimulated Cl- secretion in both rat distal colon and the T84 cell line. cAMP-mediated secretion is not affected by [HCO3-]i.

PurposeThis study aimed to verify the safety of low-dose topiramate on language development in pediatric patients with migraine.MethodsThirty newly diagnosed pediatric patients with migraine who needed topiramate were enrolled and assessed twice with standard language tests, including the Test of Language Problem Solving Abilities (TOPs), Receptive and Expressive Vocabulary Test, Urimal Test of Articulation and Phonology, and computerized speech laboratory analysis. Data were collected before treatment, and topiramate as monotherapy was sustained for at least 3 months. The mean follow-up period was 4.3±2.7 months. The mean topiramate dosage was 0.9 mg/kg/day.ResultsThe patient's mean age was 144.1±42.3 months (male-to-female ratio, 9:21). The values of all the language parameters of the TOPs were not changed significantly after the topiramate treatment as follows: Determine cause, from 15.0±4.4 to 15.4±4.8 (P>0.05); making inference, from 17.6±5.6 to 17.5±6.6 (P>0.05); predicting, from 11.5±4.5 to 12.3±4.0 (P>0.05); and total TOPs score, from 44.1± 13.4 to 45.3±13.6 (P>0.05). The total mean length of utterance in words during the test decreased from 44.1±13.4 to 45.3±13.6 (P<0.05). The Receptive and Expressive Vocabulary Test results decreased from 97.7±22.1 to 96.3±19.9 months, and from 81.8±23.4 to 82.3±25.4 months, respectively (P>0.05). In the articulation and phonology validation in both groups, speech pitch and energy were not significant, and all the vowel test results showed no other significant values.ConclusionNo significant difference was found in the language-speaking ability between the patients; however, the number of vocabularies used decreased. Therefore, topiramate should be used cautiously for children with migraine.