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Biomedical subjects

C C Chien

Publications and source records attributed to C C Chien.

At least 37 records · Page 2Linked to original sources

Sigma binding in a human neuroblastoma cell line.

Behaviorally, sigma1 agents modulate opioid analgesia. To examine possible mechanisms responsible for these interactions, we have identified a cell line containing both sigma1 and opioid receptors. [3H](+)-pentazocine binding in BE(2)-C human neuroblastoma cells is high affinity (KD 3.4 +/- 0.7 nM) and high density (Bmax 2.98 +/- 0.14 pmol/mg protein). Competition studies reveal a selectivity profile similar to that of sigma1 sites in guinea pig brain. (+)-Pentazocine has no effect upon either basal or forskolin-stimulated cyclase in the BE(2)-C cells, but cAMP accumulation is inhibited by the morphine, DPDPE and naloxone benzoylhydrazone. (+)-Pentazocine at concentrations as high as 10 microM does not affect this opioid effect, implying that sigma1/opioid interactions are not mediated at the level of the cell. This suggest that their behavioral interactions result from interacting neural circuits. Although (+)-pentazocine is without effect in the cyclase system, it does block carbachol-stimulated phosphoinositol turnover (IC50 6.5 +/- 1.14 microM). The specificity of the effect is confirmed by the ability of haloperidol (1 microM) to shift the IC50 value of (+)-pentazocine 2-fold to the right.

Adenylyl Cyclases↗

(-)-Pentazocine analgesia in mice: interactions with a sigma receptor system.

(-)-Pentazocine is active in the tailflick assay in CD-1 mice, although it shows a biphasic dose-response curve with a peak effect of only 30%. Co-administration of haloperidol shifts the dose-response curve to the left and elevates the maximal response to 70% through a blockade of sigma 1 receptors, but the curve remains biphasic. (+)-Pentazocine is inactive in all antinociceptive assays, either alone or with haloperidol. The analgesic actions of (-)-pentazocine are readily reversed by nor-binaltorphimine, but not by the mu-selective opioid receptor antagonist beta-funaltrexamine, implying a kappa 1-opioid receptor mechanism of action. This conclusion is supported by the ability of antisense oligodeoxynucleotides directed against the KOR-1 clone, which encodes the kappa 1-opioid receptor, to block (-)-pentazocine analgesia.

Analgesics, Opioid↗

Sigma antagonists potentiate opioid analgesia in rats.

In mice, activation of sigma1 receptors antagonizes opioid analgesia. Sigma antagonists potentiate opioid analgesia, implying that the anti-opioid sigma system is tonically active. Co-administration of haloperidol with the mu opioid morphine, the kappa 1 analgesic U50,488H or the kappa 3 agonist naloxone benzoylhydrazone enhances the analgesic activity of all agents. The effect results from sigma receptor blockade since (-)sulpiride, a selective D2 antagonist which does not block sigma receptors, is inactive.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Antisense oligodeoxynucleotides to the cloned delta receptor DOR-1: uptake, stability, and regulation of gene expression.

Phosphodiester antisense oligodeoxynucleotides (ODNs) directed against various domains of the cloned mouse delta receptor DOR-1 reduce delta-opioid receptor binding in vivo and in vitro. The present study examines the stability of an antisense ODN (275 nM) directed against the delta-opioid receptor and its effect on DOR-1 mRNA in cultured neuroblastoma cells and in vivo. When added to NG108-15 cells, much of the antisense ODN is degraded. However, > 1% is intact, associated with cells, and stable for at least 72 h. Northern blot analysis demonstrates that treatment of NG108-15 cells with the antisense ODN reduces the levels of a species of DOR-1 mRNA by approximately 25%. Similarly, intrathecal administration of the antisense ODN results in the accumulation of intact ODN within the spinal cord, which is stable for at least 72 h, although the levels of accumulation in vivo are lower than in vitro after either 4 or 72 h. Antisense ODN treatment lowers DOR-1 mRNA levels by approximately 25%. The loss of mRNA both in vivo and in vitro corresponds quite well to the decreases in receptor binding previously observed by our laboratory and is consistent with reduction of delta-opioid receptor protein in vitro as determined by western blot with a monoclonal antibody selective for the delta-opioid receptor. In conclusion, these studies indicate that a small, but significant, proportion of ODN is taken up by cells and remains intact for up to 72 h. This appears to be sufficient to down-regulate mRNA levels of delta-opioid receptors and their expression.

Animals↗

Blockade of U50,488H analgesia by antisense oligodeoxynucleotides to a kappa-opioid receptor.

The recently cloned kappa-opioid receptor has binding characteristics consistent with those of a kappa 1-opioid receptor. Repeated intrathecal administration of an antisense oligodeoxynucleotide against the kappa 1-opioid receptor selectively lowers U50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1- pyrrolidinyl)cyclohexyl]benzeneacetemide) analgesia (P < 0.02) without affecting mu or delta analgesia. A mismatched antisense oligodeoxynucleotide in which 4 bases had been switched is inactive against U50,488H analgesia. These studies confirm at the molecular level traditional pharmacological studies implying a distinct receptor mechanisms for kappa 1 analgesia and demonstrate the utility of antisense approaches in studies of opioid pharmacology.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Selective loss of delta opioid analgesia and binding by antisense oligodeoxynucleotides to a delta opioid receptor.

Antisense oligodeoxynucleotides (18-20 bases) to a cloned delta opioid receptor (DOR-1) lower delta binding in NG108-15 cells by 40%-50%. Changing 4 bases to generate a mismatch antisense oligodeoxynucleotide or mixing the corresponding sense and antisense oligodeoxynucleotides prior to treatment of the cells eliminates the inhibition of binding, confirming the specificity of the response. In vivo, an antisense oligodeoxynucleotide to DOR-1 given intrathecally lowers delta, but not mu or kappa 1 spinal analgesia. The mismatch antisense oligodeoxynucleotide is inactive. Delta analgesic sensitivity gradually returns by 5 days after the last antisense treatment, indicating the lack of irreversible damage or toxicity. These studies demonstrate that DOR-1 mediates delta analgesia at the level of the spinal cord and confirm at the molecular level traditional pharmacological studies implying distinct receptor mechanisms for delta, mu, and kappa 1 analgesia. The use of antisense approaches may prove valuable in understanding the receptors mediating opioid pharmacology.

Adenylyl Cyclases↗

Selective antagonism of opioid analgesia by a sigma system.

(+)Pentazocine antagonizes morphine analgesia as potently as its (-)-isomer, ruling out an opioid receptor mechanism of action and suggesting, which suggests a role for sigma 1 receptors. Systemic (+) pentazocine also reverses supraspinal or spinal morphine analgesia. 1,3-Di(2-tolyl)guanidine, a sigma ligand with no appreciable opioid receptor affinity, antagonizes morphine analgesia. The actions of both (+)pentazocine and 1,3-di(2-tolyl)guanidine are reversed by haloperidol, which has high affinity for both sigma and D2 receptors, but not by the D2-selective antagonist (-)sulpiride, which lacks activity at sigma sites. The antiopioid sigma system is tonically active. Haloperidol, but not (-)sulpiride, decreases morphine ED50 almost 2-fold. The antiopioid system modulates only mu analgesia. Unlike analgesia, (+)pentazocine does not influence morphine's inhibition of gastrointestinal transit or lethality. (+)Pentazocine also antagonizes kappa 1, kappa 3 and delta analgesia through sigma mechanisms in a haloperidol-sensitive manner. (-)Sulpiride is inactive. Alone, haloperidol enhances kappa 1, kappa 3 and delta analgesia more dramatically than morphine, which indicates that the sigma system is active against all opioid analgesic systems. Sigma systems are responsible for some strain differences in kappa receptor sensitivity. Unlike CD-1 mice, BALB-C mice are relatively insensitive toward the kappa 1 agent U50,488H and the kappa 3 analgesic naloxone benzoylhydrazone. Blockade of the sigma system with haloperidol eliminates these strain differences. In conclusion, sigma 1 systems functionally antagonize opioid analgesia without affecting morphine's effects on gastrointestinal transit or lethality. The antiopioid sigma system is tonically active and is more active against kappa analgesia than mu.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Functional antagonism of morphine analgesia by (+)-pentazocine: evidence for an anti-opioid sigma 1 system.

Both (+)-pentazocine and (-)-pentazocine antagonize morphine analgesia equally well. This lack of stereospecificity implies an non-opioid mechanism of action. The antagonism of morphine analgesia by (+)-pentazocine is reversed by haloperidol, a potent dopamine D2 and sigma receptor antagonist. The inactivity of the highly selective dopamine D2 receptor antagonist (-)-sulpiride indicates that both (+)-pentazocine and haloperidol are acting through sigma receptors. Haloperidol, but not (-)-sulpiride, also enhances morphine analgesia. Together, these results suggest the presence of a tonically active anti-opioid sigma system within the brain.

Analgesia↗

Ovarian dermoid cyst associated with tuberculosis, cystadenoma and torsion.

An 87-year-old woman who had had a lower abdominal mass for 32 years underwent a laparotomy. Surgery revealed a 21-cm left ovarian dermoid cyst with torsion. Pathologic examination showed a hemorrhagic infarct due to torsion, mucinous cystadenoma and tuberculosis within the tumor. Tuberculosis was also found in the endometrium, both ovaries, oviducts and omentum. The patient's recovery was uneventful after surgery and medical treatment. The clinical manifestations of tuberculosis can vary widely. Tuberculosis of an ovarian dermoid cyst may be silent for a long period of time unless other complications occur.

Aged↗

Internal jugular phlebectasia.

Phlebectasia, defined as abnormal venous dilation, may occur in a number of different sites. Two cases with definite diagnosis of internal jugular phlebectasia were reported. The first case was a 6-year-old girl with a bulging mass on right neck for 3 years. Angiography and CT scan showed definite diagnosis, and the bulging mass was resected from the internal jugular vein (IJV). The second case was a 66-year-old female patient, also complained of a bulging mass on her right neck. Sonogram and CT scan also showed the same diagnosis. Because it did not bother the patient, she was just under close observation. From the three kinds of diagnostic modalities, we found sonography is an effective technique because of its clarity, safety and low cost.

Aged↗

[Iron absorption in HbH disease].

We have reported that many cases of Hb H disease have a complication of iron overload without a history of multiple blood transfusion or prolonged iron therapy. We determined their iron absorption by 59Fe whole body counting in 13 such cases. Also 10 normal subjects were studied as a control group. The results showed a significant increase in iron absorption to 20.3%, in contrast to 6.9% in the normal control. This was further documented by their RBC incorporation (i.e. the percentage of orally administered) 59Fe recovered in the total RBC mass) on day 14 (13.7% vs 6.1%). The degree of ineffective erythropoiesis might not be severe considering their similar 59Fe utilization by RBC (i.e. the percentage of absorbed 59Fe recovered in the RBC) to the normals (86.3% vs. 84.3%).

Absorption↗

Does Hakka ethnic group have higher incidence of thalassemia traits in Taiwanese population?

The purpose of this survey is to find out whether Hakka group has higher incidence of thalassemia traits in our population. A total of 1,115 healthy employees from a company were screened by complete blood count (CBC) with indices. Those subjects with mean corpuscular volume (MCV) less than 80 fl were further evaluated by hemoglobin electrophoresis and modified hemoglobin H (Hb H) inclusion staining to confirm the diagnosis of beta- and alpha-thalassemia traits, respectively. We evaluated and compared the crude occurrence rates of thalassemia traits in Hakka, non-Hakka, and Taiwanese. Subjects with one or both Hakka parents had higher crude incidence of alpha-thalassemia traits than other groups of subjects, but this phenomenon wasn't found in beta-thalassemia traits.

Adult↗

Comparison of two screening methods, modified Hb H preparation and the osmotic fragility test, for alpha-thalassemic traits on the basis of gene mapping.

We evaluated 61 patients with two screening tests for alpha-thalassemia traits on the basis of endonuclease gene mapping. Comparing these two methods--the osmotic fragility test of the red cell and modified hemoglobin H inclusion staining for the sensitivity--we found that the latter was much superior to the former with 100% sensitivity in detecting heterozygous alpha-1 thalassemia and it was also specific as a confirmatory test for thalassemia traits. Red cell indices are still the basic screening tool and can be used together with modified Hb H inclusion staining. The osmotic fragility test was not better than the red cell indices and was not confirmatory. Besides the MCV, RBC, and discrimination functions, we found that RBC distribution width-standard deviation (RDW-SD) was consistently low in heterozygous alpha-1 thalassemia but not in heterozygous alpha-2 thalassemia. None of the above tests was shown to be really helpful in screening in the latter situation. We conclude that the modified Hb H inclusion staining is superior to the osmotic fragility test in screening of alpha-1 thalassemia.

Chromosome Deletion↗

[Elongated styloid process syndrome].

An elongated styloid process may be a source of craniofacial and cervical pain. The syndrome is characterized by a variety of symptoms including difficulty in swallowing, sore throat, glossodynia, headache and hemifacial pain. Sometimes, the pain is localized or radiates to the jaw and ear and may simulate pain of dental origin. Diagnosis is readily made by radiographic examination and palpating the tonsillar fossa. The only effective treatment is surgical shortening of the styloid process. Three patients, two women and a man, underwent surgery in our department for symptomatic elongation of the styloid process. The surgical procedures were conducted under general anaesthesia via a cervical approach in one patient and intraoral approach in two patients. All patients were completely relieved after styloid process resection and did not have any postoperative complications, except for cervical numbness in one case.

Adult↗

The effect of volume of epidural morphine on postoperative analgesia in patients undergoing cesarean section.

Ninety paturients undergoing elective cesarean section were included in this randomized study to compare the influence of the injected volume of epidural morphine (EM) on postoperative analgesia. Three similar groups of patients (n = 30 each) received 2 mg EM in 2 ml, 10 ml, and 20 ml saline respectively one hour after the last dose of 2% lidocaine. Pain scores (0-10) at rest (including uterine contraction pain) at the 2nd, 4th, 8th, 12th, 18th, and 24th h were compared among the three groups. There were no statistically significant differences of pain score among the three groups although lower pain score was present in the 20 ml group since the 8th h and thereafter. Regarding the number of patients who requested additional meperidine for pain relief 3 in 2 ml group, 2 in 10 ml group and 1 in 20 ml group respectively. The result may suggest that the influence of the injected volume of EM on postcesarean analgesia is not obvious.

Adult↗

Diclofenac sodium and low dose epidural morphine for postcesarean analgesia.

A randomized double-blind study of parturients after Cesarean section was undertaken to assess the efficacy of the combination of single dose intramuscular diclofenac sodium and low dose epidural morphine (EM) for postoperative analgesia. 50 parturients under epidural anesthesia were divided into 2 treatment groups: group A received 2 mg EM 30 min after the last dose of lidocaine and 3 ml normal saline i.m. at recovery room; group B received the same EM and 75 mg diclofenac i.m. postoperatively. Pain scores were compared at the 2nd, 4th, 8th, 12th, 18th, and 24th h. Results showed that group B was superior to group A in analgesic quality from the 8th h and thereafter (P less than 0.05) and 100% patients in group B were in the excellent to good analgesia categories at the 8th and 12th h record compared to 92% and 72% patients in group A respectively. Side effects were similar in both groups. The combination of NSAIDs with low dose EM could improve the analgesic quality after Cesarean section.

Adult↗

Significant functional recovery after delayed evacuation of traumatic thoracic intramedullary hematoma: case report.

A patient with traumatic thoracic intramedullary hematoma underwent operation 1 month postinjury. Evacuation and syringosubarachnoid shunting resulted in return of bladder control and of sufficient strength in the lower extremities to permit independent walking. The outcome is discussed in light of the literature on traumatic intramedullary hematoma. The value of magnetic resonance imaging is noted. We suggest an aggressive diagnostic and therapeutic approach toward intramedullary spinal cord hematomas.

Hematoma↗