BACKGROUND: Left ventricular hypertrophy (LVH) has been known as an important predictor of prognosis of cardiovascular disease. Carboxy-terminal propeptide of procollagen type I (PIP) is related with myocardial fibrosis. We sought to analyze the differences in the characteristics of LVH, myocardial fibrosis, and LV functions among hypertension (HBP), diabetes mellitus (DM) and chronic renal failure (CRF). METHODS: We enrolled consecutive patients with LVH. Patients were grouped as HBP (n=50), DM (n=41), CRF (n=31). Age and sex-matched normal control was also enrolled (n=32). Echocardiography and blood sampling for serum PIP level measuring was performedin all participants. RESULTS: There were no differences in baseline characteristics except systolic blood pressure among four groups. In three patients groups, their LV mass indices were significantly increased than control. Serum PIP level in CRF was much higher than others (CRF 1505.5 vs. HBP 868.7 vs. DM 687.5 vs. control 826.4, p<0.0001). LV diastolic and systolic function evaluated by E', E/E, S' and midwall fractional shortening was significantly decreased in three patients groups. However, LAVi was significantly elevated and LV ejection fraction was significantly decreased in CRF compared to others. In correlation analysis, indices of diastolic function were weakly, but statistically correlated with PIP (E': r=0.234, p=0.006; LAVi: r=0.231, p=0.006). CONCLUSION: In CRF, LV function was more deteriorated and serum PIP was more elevated when compared to HBP or DM. Therefore, myocardial fibrosis may play an important role to LV dysfunction as well as LV hypertrophy in CRF in some degree.
Blood Pressure ; Cardiovascular Diseases ; Collagen Type I ; Diabetes Mellitus ; Echocardiography ; Fibrosis ; Humans ; Hypertension ; Hypertrophy ; Hypertrophy, Left Ventricular ; Kidney Failure, Chronic ; Prognosis

OBJECTIVE: Angiogenesis is central role to both the proliferation and metastasis of malignant tumor. The intense interest in angiogenesis has also lead to a re-examination of the activity of established cytotoxic agents which are known to be an antiangiogenic effect anecdotally. In this study, anti-angiogenic effect of cisplatin, paclitaxel and thalidomide was evaluated in human ovarian cancer cell lines and cervical cancer cell line. METHODS: Human ovarian cancer cell line A2780, cisplatin resistant human ovarian cancer cell line A2780-CDDP, human breast cancer cell line MCF-7, and squamous cell uterine cervical carcinoma cell line SiHa were used to evaluate the level of mRNA and protein expression of VEGF, bFGF and TSP-1, 2 before and after the treatment with cisplatin, paclitaxel, and thalidomide using RT-PCR, protein extraction, and Western blot. The results were analyzed with Wilcoxon signed rank test in the SAS ver 8.1. RESULTS: Targeted mRNAs were synthesized as 212 bp VEGF, 238 bp bFGF, and 492 bp band sized except mRNA of TSP-2 via RT-PCR. The protein of VEGF and bFGF were appeared as 21KDa and 17 KDa size, however, the protein of TSP-1 was not appeared through western blot. No effect of cisplatin on protein expression was measured in these cell lines, but paclitaxel influenced the expression of bFGF in MCF-7 cell line and the expression of TSP-1 in MCF-7 and SiHa cell lines. TSP-1 expression was influenced by thalidomide in A2780 cell line. The protein expression of VEGF and bFGF were not influenced following treatment with cisplatin, paclitaxel, and thalidomide. CONCLUSION: These results were suggested that bFGF and TSP-1 will be used as a target gene for the assay of antiangiogenic effect of paclitaxel in breast and uterine cervical cancer tissue and TSP-1 will be used as that of thalidomide in ovarian cancer. Furthermore, thalidomide will be tried as an adjunctive agent for the improvement of the survival in the case of the patient with ovarian cancer.
Blotting, Western ; Breast ; Breast Neoplasms ; Cell Line* ; Cisplatin ; Cytotoxins* ; Humans ; MCF-7 Cells ; Neoplasm Metastasis ; Ovarian Neoplasms ; Paclitaxel ; RNA, Messenger* ; Thalidomide ; Thrombospondin 1 ; Uterine Cervical Neoplasms ; Vascular Endothelial Growth Factor A

BACKGROUND/AIMS: Tamoxifen is a widely used anticancer drug for breast cancer with frequent gastrointestinal side effects. Changes in gastrointestinal motility is associated with altered activities of membrane ion channels. Ion channels have important role in regulating membrane potential and cell excitability. This study was performed to investigate the effects of tamoxifen on the membrane ionic currents in colonic smooth muscle cells. METHODS: Murine colonic smooth muscle cells were isolated from the proximal colon using collagenase, and the membrane currents were recorded using a whole-cell patch clamp technique. RESULTS: Two types of voltage-dependent K+ currents were recorded (A-type and delayed rectifier K+ currents). Tamoxifen inhibited both types of voltage-dependent K+ currents in a dose-dependent manner. However, tamoxifen did not change the half-inactivation potential and the recovery time of voltage-dependent K+ currents. Chelerythrine, a protein kinase C inhibitor or phorbol 12, 13-dibutyrate, a protein kinase C activator did not affect the voltage-dependent K+ currents. Guanosine 5'-O-(2-thio-diphosphate) did not affect the tamoxifen-induced inhibition of voltage-dependent K+ currents. Tamoxifen inhibited voltage-dependent Ca2+ currents completely in whole-test ranges. CONCLUSIONS: These results suggest that tamoxifen can alter various membrane ionic currents in smooth muscle cells and cause some adverse effects on the gastrointestinal motility.
Animals ; Antineoplastic Agents, Hormonal/*pharmacology ; Calcium Channels/drug effects ; Colon/*drug effects/physiology ; English Abstract ; In Vitro ; Membrane Potentials ; Mice ; Myocytes, Smooth Muscle/*drug effects/physiology ; Potassium Channels/*drug effects ; Tamoxifen/*pharmacology

In addition to the central and the peripheral nervous system, calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) has been identified throughout the enteric nervous system. Several functions of the CGRP in gastrointestinal (G-I) tract has been identified, but the effect of CGRP on G-I motility is unclear. The distribution of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) in the murine small bowel were studied by using immunohistochemistry, also analyzed functionally by using electrophysiological method. Immunohistochemical studies demonstrated that CGRP-LI is localized in both nerve fibers and myenteric ganglion cells in the whole-mount preparation of murine small intestine. Double labelling with CGRP and c-kit investigated by confocal microscope was shown that CGRP-LI enteric nerve fiber surrounded the c-kit positive interstitial cells of Cajal (ICC). Electrophysiological finding revealed that treatment of CGRP inhibited electrical activity on culture ICC. Our results suggest a CGRP innervation of murine small bowel ICC. The released CGRP from enteric nerve terminals may induce relaxation of small bowel through the inhibition of ICC.
Animals ; Calcitonin Gene-Related Peptide* ; Calcitonin* ; Enteric Nervous System ; Ganglion Cysts ; Immunohistochemistry ; Interstitial Cells of Cajal ; Intestine, Small* ; Mice ; Nerve Fibers ; Peripheral Nervous System ; Relaxation

Interstitial Cells of Cajal (ICC) are pacemaker cells that generates slow waves and drive spontaneous mechanical contractions of gastrointestinal smooth muscle. Slow waves are generated the periodic activation of spontaneous inward currents (pacemaker currents). We studied the modulation of pacemaker activities by bradykinin (10-8 M) in cultured ICC with the whole cell patch-clamp technique, and the localization of bradykinin-2 receptor-immunoreactivity using double labelling immunohistochemistry in the murine small intestine. Externally applied bradykinin produced membrane depolarization in current-clamping mode. At a -70 mV of holding potential bradykinin increased tonic inward pacemaker currents. Double labelling with bradykinin-2 receptor and and c-kit was shown that ICC expressed the bradykinin-2 receptor-immunoreactivity. These results suggest that bradykinin modulates electrical activities of ICC via bradykinin-2 receptor, which may regulate gastrointestinal motility.
Animals ; Bradykinin* ; Gastrointestinal Motility ; Immunohistochemistry ; Interstitial Cells of Cajal* ; Intestine, Small* ; Membranes ; Mice* ; Muscle, Smooth ; Patch-Clamp Techniques ; Receptors, Bradykinin*

The vanilloid receptor type-1 (VR1) is a nonselective cation channel activated by capsaicin and can be act as mediator of chemical and physical stimuli that elicit pain. The presence of VR1 in the dorsal root, trigeminal and nodose ganglia has been firmly established, but it unclear in the mouse intestinal wall. The distribution of VR1 receptors in mouse afferent neurons innervating the intestinal tract was investigated by immunohistochemistry. Also small and large intestines were dual-labelled with antibody for VR1 and marker for interstitial cells of Cajal (c-kit). VR1-immunopositive cells were localized on fine fibers in myenteric plexus and expressed weakly myenteric ganglia. The majority of VR1-immunopositive fibers are not colocalized with or apposed to c-kit positive interstitial cells of Cajal. Also electrophysiologically capsaicin had no effect on cultured interstitial cells of Cajal. It is concluded that VR1-immunoreactive intestinal nerves are mainly distributed in myenteric plexus of murine intestinal wall, and vanillod may be not directly related to interstitial cells of Cajal in regulation of intestinal motility.
Animals ; Capsaicin ; Ganglia ; Gastrointestinal Motility ; Immunohistochemistry ; Interstitial Cells of Cajal ; Intestines ; Mice* ; Myenteric Plexus* ; Neurons, Afferent ; Nodose Ganglion ; Spinal Nerve Roots

The vanilloid receptor type-1 (VR1) is a nonselective cation channel activated by capsaicin and can be act as mediator of chemical and physical stimuli that elicit pain. The presence of VR1 in the dorsal root, trigeminal and nodose ganglia has been firmly established, but it unclear in the mouse intestinal wall. The distribution of VR1 receptors in mouse afferent neurons innervating the intestinal tract was investigated by immunohistochemistry. Also small and large intestines were dual-labelled with antibody for VR1 and marker for interstitial cells of Cajal (c-kit). VR1-immunopositive cells were localized on fine fibers in myenteric plexus and expressed weakly myenteric ganglia. The majority of VR1-immunopositive fibers are not colocalized with or apposed to c-kit positive interstitial cells of Cajal. Also electrophysiologically capsaicin had no effect on cultured interstitial cells of Cajal. It is concluded that VR1-immunoreactive intestinal nerves are mainly distributed in myenteric plexus of murine intestinal wall, and vanillod may be not directly related to interstitial cells of Cajal in regulation of intestinal motility.
Animals ; Capsaicin ; Ganglia ; Gastrointestinal Motility ; Immunohistochemistry ; Interstitial Cells of Cajal ; Intestines ; Mice* ; Myenteric Plexus* ; Neurons, Afferent ; Nodose Ganglion ; Spinal Nerve Roots

The interstitial cells of Cajal (ICCs) are the pacemaker cells in gastrointestinal tract and generate electrical rhythmicity in gastrointestinal muscles. Therefore, ICC may be modulated by endogenous agents such as neurotransmitter, hormones, and prostaglandins (PGs). In the present study, we investigated the effects of prostaglandins, especially PGE2, on pacemaker currents in cultured ICCs from murine small intestine by using whole-cell patch clamp techniques. ICCs generated spontaneous slow waves under voltage-clamp conditions and showed a mean amplitude of -452+/-39 pA and frequency of 18+/-2 cycles/min (n=6). Treatments of the cells with PGE2 (1muM) decreased both the frequency and amplitude of the pacemaker currents and increased the resting currents in the outward direction. PGE2 had only inhibitory effects on pacemaker currents and this inhibitory effect was dose-dependent. For characterization of specific membrane EP receptor subtypes, involved in the effects of PGE2 on pacemaker currents in ICCs, EP receptor agonists were used: Butaprost (1muM), EP2 receptor agonist, reduced the spontaneous inward current frequency and amplitude in cultured ICCs (n=5). However sulprostone (1muM), a mixed EP1 and EP3 agonist, had no effects on the frequency, amplitude and resting currents of pacemaker currents (n=5). SQ-22536 (an inhibitor of adenylate cyclase; 100muM) and ODQ (an inhibitor of guanylate cyclase; 100muM) had no effects on PGE2 actions of pacemaker currents. These observations indicate that PGE2 alter directly the pacemaker currents in ICCs, and that the PGE2 receptor subtypes involved are the EP2 receptor, independent of cyclic AMP- and GMP-dependent pathway.
Adenylyl Cyclases ; Dinoprostone* ; Gastrointestinal Tract ; Guanylate Cyclase ; Interstitial Cells of Cajal* ; Intestine, Small* ; Membranes ; Muscles ; Neurotransmitter Agents ; Patch-Clamp Techniques ; Periodicity ; Prostaglandins

We report a case of accidental intrathecal administration of Nucomyt(R)(acetylcysteine), a mucolytic agent used for intratracheal instillation. A 21-year-old healthy female with a complete syndactyly at the 4th and 5th toes was scheduled for a web release under spinal anesthesia. Immediately after accidental intrathecal administration of Nucomyt(R)2.4 ml instead of bupivacaine for spinal anesthesia, tonic extension developed at first in the lower extremities and then the upper extremities, too. Thiopental sodium 200 mg was injected intravenously twice. Endotracheal general anesthesia with N2O- enflurane-vecuronium was maintained for the operation for about two hours. For about 1 hour after emergence of general anesthesia, tonic extension intermittently developed in the lower extremities and was controlled with midazolam. Mild elevated blood pressure, tachycardia, tachypnea, high fever (up to 38.5degrees C) and respiratory acidosis occurred. Thirty minutes later, she became mentally clear with a normal neurologic examination. No delayed sequelae were detectable at a follow-up visit 1 month and 1 year after surgery.
Acetylcysteine* ; Acidosis, Respiratory ; Anesthesia, General ; Anesthesia, Spinal ; Blood Pressure ; Bupivacaine ; Female ; Fever ; Follow-Up Studies ; Humans ; Lower Extremity ; Midazolam ; Neurologic Examination ; Syndactyly ; Tachycardia ; Tachypnea ; Thiopental ; Toes ; Upper Extremity ; Young Adult

Interstitial cells of Cajal (ICC) are the pacemakers in gastrointestinal slow wave, and also transduce signal inputs from the enteric nervous system to smooth muscle. The abnormal motility corresponded to a lack or decreasing of ICC and a disruption of electrical slow waves. So we developed partial obstruction model in murine small intestine, and found that ICC and electrical slow wave were absent or decreased oral to the occlusion site in previous study. In an additional series of experiments, we examined the ability of tissue regenerate the ICC phenotype and normal electrical slow waves after surgical treatment to relieve the mechanical obstruction, and the animals were allowed to recover for 1~2 months. Removal of the obstruction led to the normal gross appearance and the redevelopment of ICC and recovery of slow wave activity within 30 days. These data demonstrate the plasticity of ICC networks in response to partial obstruction, and suggest that adult tissue retain the ability to regenerate functional ICC. This model may be useful for estimating molecular factors responsible for the regulation of the ICC phenotype. More work is needed to find out the factors in ICC for the therapy of intestinal motility disorders.
Adult ; Animals ; Enteric Nervous System ; Gastrointestinal Motility* ; Humans ; Interstitial Cells of Cajal* ; Intestine, Small ; Mice ; Muscle, Smooth ; Phenotype ; Plastics*