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Biomedical subjects

P C Chang

Publications and source records attributed to P C Chang.

At least 19 recordsLinked to original sources

Kappa opioid receptors in rat spinal cord: sex-linked distribution differences.

Activation of kappa opioid receptors (KORs) in the spinal cord can diminish nociception. Humans and rodents show sex differences in the analgesia produced by KOR agonists, and female rats show fluctuations in KOR density and sensitivity across the estrous cycle. However, it is unclear whether there are sex differences in the amount and/or distribution of spinal KORs. In the present study, immunocytochemically labeled KORs were examined in laminae I and II of the lumbosacral spinal dorsal horn of male and normally cycling female Sprague-Dawley rats. The basic pattern of KOR labeling was determined in both sexes using qualitative electron microscopy (EM), and sex-linked differences in the density and subcellular distribution of KOR immunoreactivity were determined with quantitative EM and light microscopy. KOR labeling was visualized with immunoperoxidase for optimally sensitive detection, or with immunogold for precise subcellular localization. By EM, the general pattern of KOR immunoreactivity was similar in males and females. KOR immunoreactivity was common in dendrites, axons, and axon terminals, and was in a few glia and neuronal somata. Most KOR-immunoreactive (-ir) axons were fine-diameter and unmyelinated. Most KOR-ir terminals were small or medium-sized, and a minority formed asymmetric or symmetric synapses with unlabeled dendrites. KOR immunoreactivity was associated both with the plasma membrane and with cytoplasmic organelles, notably including dense core vesicles in terminals. Light microscopic densitometry revealed that KOR immunoreactivity was significantly denser in estrus and proestrus females than in males. By EM, the distribution of KOR-immunogold labeling within axon terminals differed, with a greater proportion of cytoplasmic KOR labeling in estrus females compared with males. In contrast, the abundance and types of KOR-immunoperoxidase-labeled profiles did not show sex-linked differences. We conclude that in both sexes, KORs are positioned to influence both pre- and postsynaptic neurotransmission and are present in morphologically heterogeneous neuron populations. These findings are consistent with complex consequences of KOR activation in the spinal cord. In addition, the presence of increased KOR density and proportionally elevated intracellular KORs in proestrus/estrus females suggests a basis for sex-linked differences in KOR-mediated antinociception.

Animals↗

Neurons with mu opioid receptors interact indirectly with enkephalin-containing neurons in the rat dentate gyrus.

In the dentate gyrus, mu opioid receptors (MORs) and their enkephalin agonists have overlapping distributions and influence excitability and plasticity. Released endogenous enkephalins can activate at least some of these MORs; however, whether these interactions involve synaptically associated profiles or more distant associations and whether some subcellular compartments (e.g., terminals or dendrites) are more likely to be targeted than others are not known. To elucidate the relationships between potential sites of enkephalin release and MORs, MOR1 and leucine-enkephalin (LE) immunoreactivities were localized in the hilus by electron microscopy, using immunoperoxidase and immunogold markers. Of the 573 MOR-immunoreactive (ir) profiles analyzed, most were axons and terminals (51 and 30%, respectively), and fewer were dendrites (12%), glia (3%), or unclassifiable (4%). Most MOR-ir profiles resembled interneuron processes, while most LE-ir terminals resembled mossy fibers. One third of MOR-ir profiles were within 3 microm and approximately half were within 4 microm of the nearest LE-ir profile. In contrast, few (3%) MOR-ir profiles contacted LE-ir profiles; only 16% of these contacts included observable synapses, and very few profiles (0.5%) colocalized MOR and LE immunoreactivity. MOR-ir axons, terminals, and dendrites were not distributed differently relative to LE-ir profiles. These results suggest that activation of hilar MORs by LE usually involves short-range volume transmission and that dendritic MORs are as likely as axonal and terminal MORs to be activated by released LE. However, the greater abundance of MOR-ir axons and terminals compared to dendrites indicates that presynaptic profiles are a more prominent target for enkephalins and exogenous MOR agonists such as morphine.

Animals↗

Molecular characterization of Newcastle disease viruses isolated from recent outbreaks in Taiwan.

A reverse transcription-polymerase chain reaction (RT-PCR) was described which amplified a portion of the F and HN genes of Newcastle disease virus (NDV) isolated from recent outbreaks in Taiwan. The F protein plays an important role in determining the virulence of NDV strains. Sequencing of a region specifying the F protein cleavage site was therefore undertaken and this verified the correlation between deduced amino sequences and pathogenicity. Analysis of the deduced amino acid sequences of the F protein cleavage site showed that all recent Taiwanese isolates in 1999 were velogenic viruses. All the virulent viruses have the amino acid sequence 112RRQKR116 for the C-terminus of the F2 protein and phenylanine (F) at the N-terminus of the F1 protein, residue 117. A phylogenetic tree based on the nucleotide sequences of the F gene revealed that recent Taiwanese NDV isolates responsible for recent outbreaks were classified into two distant genotypes (VI and VII). Genotype VI virus is the first finding in Taiwan and has a highly genetic similarity to European isolates, suggesting that they might have originated from a common ancestor.

Amino Acid Sequence↗

Identification and subtyping of avian influenza viruses by reverse transcription-PCR.

Avian influenza viruses have 15 different hemagglutinin (HA) subtypes (H1-H15). We report a procedure for the identification and HA-subtyping of avian influenza virus by reverse transcription-PCR (RT-PCR). The avian influenza virus is identified by RT-PCR using a set of primers specific to the nucleoprotein (NP) gene of avian influenza virus. The HA-subtypes of avian influenza virus were determined by running simultaneously 15 RT-PCR reactions, each using a set of primers specific to one HA-subtype. For a single virus strain or isolate, only one of the 15 RT-PCR reactions will give a product of expected size, and thus the HA-subtype of the virus is determined. The result of HA-subtyping was then confirmed by sequence analysis of the PCR product. A total of 80 strains or isolates of avian influenza viruses were subtyped by this RT-PCR procedure, and the result of RT-PCR gave an excellent (100%) correlation with the result of the conventional serological method. The RT-PCR procedure we developed is rapid and sensitive, and could be used for the identification and HA-subtyping of avian influenza virus in organ homogenates.

Animals↗

Laparoscopic closure of patent canal of Nuck for female indirect inguinal hernia.

STUDY OBJECTIVE: To determine the efficacy of concomitant laparoscopic closure of the patent canal of Nuck in treatment of indirect inguinal hernias in women. DESIGN: Prospective clinical trial (Canadian Task Force classification II-2). SETTING: University-associated tertiary care referral center. PATIENTS: Six women scheduled for laparoscopy for gynecologic indications. Intervention. Concomitant simple closure of the patent canal of Nuck from the peritoneal cavity during laparoscopic surgery. MEASUREMENTS AND MAIN RESULTS: Inguinal hernias were repaired in all six patients, with no recurrence. CONCLUSION: l Laparoscopic closure of the patent canal of Nuck is an easy, safe, and effective treatment of indirect inguinal hernias in women. (J Am Assoc Gynecol Laparosc 8(1):143-146, 2001)

Adult↗

Concomitant closure of patent canal of Nuck during laparoscopic surgery: case report.

Indirect inguinal hernia is neglected by many female patients. When women undergo laparoscopy for infertility work-up or other gynaecological conditions, the hernia appears pressurized by the pneumoperitoneum. A large opening on the peritoneum followed by the patent canal of Nuck-as seen in the patient in this case report-is accompanied by a bulge above the labia major. This situation was treated with simple ligation of the canal of Nuck from the internal inguinal ring, and the vulvar bulging mass quickly disappeared, even while under pneumoperitoneal pressure. Laparoscopic hernia repair is currently performed with a mesh prosthesis to cover the defect; however, in female patients it seems unnecessary to use such an invasive method designed largely for males. According to our experience, the concomitant simple closure method for female indirect inguinal hernia is a quick and simple procedure, and deals with the problem during the same laparoscopy. In addition, disappearance of the bulging mass under the pneumoperitoneum offers a useful diagnostic test to secure hernia management.

Adult↗

Determination of biogenic amines in fish implicated in food poisoning by micellar electrokinetic capillary chromatography.

A micellar electrokinetic capillary chromatography (MECC) method for the simultaneous determination of seven biogenic amines in fish was developed. The peaks of all components were successfully separated within 11.5 min. MECC was performed with 0.06 M sodium deoxycholate in 0.02 M borate buffer (pH 9.2)-methanol (95:5, v/v) solvent. The average recoveries for all components ranged from 84.4 to 100.3%. The application of this method to detect amines in fried marlin fillet implicated in a food poisoning incident indicated that a high level (56.24 mg/100 g) of histamine was present in the sample. Another 10 fish samples collected from markets were also analyzed and did not contain detectable levels of histamine (<2.5 mg/100 g).

Animals↗

Kappa opioid receptors in rat spinal cord vary across the estrous cycle.

Kappa opioid receptors (KORs) were immunocytochemically localized in the lumbosacral spinal cord of female rats in different stages of the estrous cycle to examine the influence of hormonal status on receptor density. KOR labeling was primarily in fine processes and a few neuronal cell bodies in the superficial dorsal horn and the dorsolateral funiculus. Quantitative light microscopic densitometry of the superficial dorsal horn revealed that rats in diestrus had significantly lower KOR densities than those in proestrus or estrus. This suggests that female reproductive hormones regulate spinal KOR levels, which may contribute to variations in analgesic effectiveness of KOR agonists across the estrous cycle.

Animals↗

Protein constituent contributes to the hypotensive and vasorelaxant activities of Cordyceps sinensis.

Cordyceps sinensis is a herb medicine in China for the treatment of general debility after sickness and for persons of advanced age. In the present study, cordyceps sinensis was extract by phosphate buffer saline (PBS) and dialyzed overnight against PBS using a membrane cut off at 3,500 dalton molecular weight. The resulting macromolecule fraction (defined as CS) was assayed in anesthetized rats for hypotensive effects and in isolated aorta for vasorelaxant effects. Intravenous injection of CS (8,16, 24 and 32 mg/kg, respectively) suppressed significantly the mean arterial pressure (MAP) in a dose-dependent manner. 32 mg/kg of CS induces the maximal hypotensive response with a 58 +/- 4 mm Hg (from 107 +/- 6 to 49 +/- 3 mm Hg) change in MAP and a over 45 min action duration. In aortic rings precontracted with phenylephrine treatment with CS between 0.5 and 500 microg/ml induced dose dependent relaxation. Maximal vasorelaxant response evoked by 150 microg/ml CS was 68.9 +/- 7.3%. Furthermore, CS-induced vasorelaxation is mediated by the endothelium possibly by stimulating the release of the nitric oxide and endothelium-derived hyperpolarizing factor. In conclusion, the present study revealed that presence of a constituent in CS which reduces MAP by relaxing the vascular beds directly. However, the effect may be caused by a single active ingredient or by the combined action of many active agents found in the extract.

Adenosine↗

The ACE insertion/deletion polymorphism has no influence on progression of renal function loss in autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) shows a variable clinical course that is not fully explained by the genetic heterogeneity of this disease. We looked for a possible genetic modifier, the ACE I/D polymorphism, and its influence on progression towards end-stage renal failure (ESRF). METHODS: Forty-nine ADPKD patients who reached ESRF <40 years, and 21 PKD1 patients who reached ESRF > 60 years or were not on dialysis at 60 years of age were recruited. Clinical data were provided by questionnaires. Blood was collected for the determination of the ACE insertion/deletion (I/D) polymorphism genotype. The ACE genotype was also determined in a general, control PKD1 group (n=59). RESULTS: Patients who reached ESRF <40 years had significantly more early onset hypertension than patients reaching ESRF >60 years (80% vs 21%; P<0.001). The ACE genotype distribution showed no differences between the groups of the rapid progressors (DD 20%, ID 56%, II 24%), the slow progressors (DD 29%, ID 52%, II 19%) and the general PKD1 control population (DD 31%, ID 47%, II 22%). CONCLUSION: There is no relationship between progression towards ESRD and the ACE I/D polymorphism in ADPKD patients.

Adult↗

The angiotensin-converting enzyme gene polymorphism and responses to angiotensins and bradykinin in the human forearm.

The deletion (D) allele of the angiotensin-converting enzyme (ACE) is associated with high ACE levels. Subjects homozygous for the D allele should therefore exhibit enhanced angiotensin I-induced vasoconstrictor responses and diminished bradykinin-induced vasodilator responses as compared with subjects homozygous for the insertion (I) allele. In eight II and eight DD normotensive male subjects, angiotensin I, bradykinin, and angiotensin II were infused in the forearm. Changes in forearm blood flow were registered with venous occlusion plethysmography. Blood was sampled to quantify angiotensin I to II conversion. Plasma ACE levels were 60% higher, and DD subjects showed an enhanced response to angiotensin I infusion (p < 0.05). No differences in angiotensin I to II conversion, angiotensin H vasoconstriction, and bradykinin vasorelaxation were found. The ACE-inhibitor enalaprilate inhibited angiotensin I-induced vasoconstriction, but did not significantly affect bradykinin-induced vasodilation. The AT1-receptor antagonist losartan (3,000 ng/kg/min) inhibited angiotensin II-induced vasoconstriction. In conclusion, subjects with the DD genotype display an enhanced vasoconstrictor response to angiotensin I, which cannot be explained on the basis of a similarly enhanced angiotensin I to II conversion rate or a difference in vascular reactivity. Possibly therefore, differences in angiotensin I to II conversion occur within the vascular wall only, at a site that does not readily equilibrate with blood plasma.

Adult↗

Long-term outcome of surgical revascularization in ischemic nephropathy: normalization of average decline in renal function.

OBJECTIVE: Renovascular disease may lead to ischemia of the nephrons and to fibrosis, which is generally considered to be irreversible and progressive. We investigated the potential of revascularization to recover and stabilize renal function in patients with ischemic nephropathy. METHODS: In a retrospective analysis of all our 61 patients with ischemic nephropathy who underwent treatment with surgical revascularization, we determined the long-term course of renal function decline with an estimated glomerular filtration rate (EGFR; Cockcroft and Gault formula). With the assumption of normal renal function at age 25 years, the preoperative slope of EGFR and the postoperative slope of EGFR were determined from the EGFR before surgery, at the short-term follow-up examination (on average, 8 months after surgery), and at the long-term follow-up examination (on average, at 47 months after surgery). These declines in renal function were compared with EGFR values in age-matched and sex-matched samples from a large cross-sectional population study. RESULTS: The overall surgical mortality rate amounted to 13.1%. Five patients became dialysis dependent-two with preexisting end-stage renal disease and three at later follow-up examination-and two patients, who before surgery were dialysis dependent, could be withdrawn from dialysis treatment. Shortly after the operation, the mean EGFR level had increased from 28.3 to 43.1 mL/min/1.73 m2 ( P <. 01). The rate of decline in renal function had decreased from an estimated -2.57 mL/min/1.73 m2/year before surgery (weighted mean: interquartile range, -2.71 to -1.98) to -0.66 mL/min/1.73 m2/year (weighted mean: interquartile range, -2.00 to -0.18) in the short-term interval to the long-term interval, which was even slightly better than the slope of -0.84 mL/min/1.73 m 2/year in the age-matched and sex-matched control population. CONCLUSION: Surgical revascularization in selected patients with renovascular disease and ischemic nephropathy restores renal function and makes the average long-term rate of decline in renal function equal to that of the general population. This indicates that in most patients a "point-of-no-return" has not yet been passed even though their renal function is already markedly impaired before surgery. Therefore, in well-selected patients with ischemic nephropathy, considerable improvement of renal function can be realized.

Adult↗

Pharmacokinetics of interleukin-2 in two anephric patients with metastatic renal cell cancer.

BACKGROUND: Most patients with metastatic renal cell carcinoma (RCC) have undergone unilateral- and some bilateral nephrectomy. Because interleukin-2 (IL-2) is thought to be mainly cleared via the kidneys, we investigated whether IL-2 treatment is safe in anephric patients. PATIENTS AND METHODS: The pharmacokinetics of i.v. bolus, i.v. infusion and s.c. recombinant IL-2 were investigated in two anephric patients with progressive metastatic RCC. RESULTS: Following i.v. bolus administration of IL-2, plasma half-lives of 126 and 84 minutes respectively, and plasma clearances of 151 ml/min and 273 ml/min respectively, were measured in the two patients. In one patient plasma clearance of IL-2 was enhanced to 760 ml/min after continuous i.v. infusion of 4 and 6 million IU IL-2/24 hours, as compared to a clearance of 310 ml/min at a dose of 2 million IU IL-2/24 hours. In the other patient, during IL-2 infusion of 2, 4 or 6 x 10(6) IU/24 hours, each over the course of 3 days, plasma clearance of IL-2 increased from 311 to 761, and to 687 ml/min, respectively. IL-2 could not be detected in haemo- or peritoneal dialysates. CONCLUSIONS: IL-2 plasma half-life is only moderately prolonged in anephric patients as compared to patients with normal renal function. Based on our findings, intravenous or subcutaneous treatment of anephric patients with IL-2 seems feasible.

Aged↗

Acute hyperglycaemia in the forearm induces vasodilation that is not modified by hyperinsulinaemia.

OBJECTIVE: To evaluate whether acute elevations of local plasma glucose concentrations could influence forearm blood flow (FBF) and how this interacts with local hyperinsulinaemia in healthy volunteers. METHODS: Using the perfused forearm technique, in random order, glucose 20% or saline 0.9% as a control was infused in three dose steps (0.3, 1.0, and 3.0 ml/min) for 5 min each in eight healthy men. The infusion experiments were repeated, in random order, during local hyperinsulinaemia by intra-arterial infusion of insulin 0.05 mU/kg/min. The ratio of FBF of the infused over the FBF in the control arm (FR) was measured at 15-sec intervals during the infusions. RESULTS: Glucose infusion increased the FR dose-dependently by 172%+/-39% (M+/-SE) at the highest dose (P < 0.01). During hyperinsulinaemia the glucose-induced increase in FR was significantly (P < 0.01) less, 96%+/-26%, however, when changes in FR or forearm vascular resistance were related to the plasma glucose concentrations both glucose infusions were equipotent. The saline infusions induced small increases in FR of 27+/-5% (P < 0.01) and 24+/-11% (P > 0.05), without or with insulin respectively. The changes in FR during the saline infusions were much smaller than during the glucose infusions (P < 0.01). During the glucose infusions small but significant increases in FBF and venous plasma glucose in the non-infused forearm appeared, indicating carry-over effect and the possibility of a very low threshold for glucose-induced vascular effects. CONCLUSIONS: High, local levels of glucose in the forearm have a vasodilator effect on resistance vessels in skeletal muscle of the forearm that is not modified by local hyperinsulinaemia. Indications were found that the threshold for this glucose-induced vasodilation may be remarkably low, but this needs to be studied more formally.

Acute Disease↗

Effects of sodium depletion on the role of AT1- and alpha-adrenergic receptors in the regulation of forearm vascular tone in humans.

OBJECTIVE: Sodium depletion stimulates the renin-angiotensin and sympathetic nervous systems, which may affect the role of each of these systems in the regulation of vascular tone. We investigated the influence of sodium depletion on the roles of the angiotensin II type 1 receptor and the alpha1- and alpha2-adrenergic receptors, and on nitric oxide generation, in the regulation of human forearm vascular tone. SUBJECTS AND METHODS: We studied the effects of the angiotensin II type 1 receptor antagonist losartan (0.1-3 microg/kg per min), angiotensin II (0.01-10 ng/kg per min), the alpha1- and alpha2-adrenoceptor antagonists doxazosin (3-100 ng/kg per min) and yohimbine (0.5-4 microg/kg per min) and the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (L-NMMA; 7.5-60 microg/kg per min) on forearm blood flow in control subjects (n = 12) and sodium-depleted subjects (n = 11). Sodium depletion was achieved by 3 days of pretreatment with 40 mg furosemide twice a day and a sodium-restricted diet. Forearm blood flow was measured by venous occlusion plethysmography. RESULTS: Sodium depletion resulted in activation of the renin-angiotensin and sympathetic nervous systems, as indicated by increased levels of plasma renin, aldosterone and heart rate (P < 0.05). Blood pressure remained unchanged. Losartan at the highest dose increased forearm blood flow in the sodium-depleted group by 42 +/- 9%, but had no effect in controls (P < 0.05). Both doxazosin and yohimbine caused an increased vasodilatory effect in the sodium-depleted versus the control group (228 +/- 42 versus 83 +/- 13% and 192 +/- 24 versus 95 +/- 8%, respectively; P < 0.05). The constrictor effects by angiotensin II and L-NMMA of -65 +/- 6% and -79 +/- 4%, respectively, in controls were unchanged by sodium depletion. CONCLUSIONS: In sodium-depleted subjects, endogenous angiotensin II appears to play a role in the regulation of forearm vascular tone, in contrast to sodium-replete conditions. Furthermore, in these subjects the role of alpha1- and alpha2-adrenoceptors in the regulation of forearm vascular tone was enhanced compared with control conditions. Neither the forearm vascular effects of exogenously infused angiotensin II nor those of baseline nitric oxide production were influenced by sodium depletion.

Adrenergic alpha-Antagonists↗

Influence of losartan and nicardipine on the contractile responses of human subcutaneous arteries and veins to angiotensin II.

In the human forearm vascular bed, the arterial constrictor effects of angiotensin II were found to be caused by an AT1-receptor mediated calcium influx, while the venous constrictor effects appeared to be independent of L-type calcium channels. In this study, we investigated the influences of the AT1-receptor antagonist losartan and the calcium channel blocker nicardipine on the angiotensin II-induced constriction of small isolated subcutaneous arteries and veins obtained from human mammary tissue. Subcutaneous arteries and veins were isolated from mammary tissue from 9 healthy women who underwent breast reduction surgery. Effects of angiotensin II (0.3 nM to 1 mM), losartan (0.1 mM) and nicardipine (0.1 mM) were investigated in a myograph set up. Identification of arteries and veins was confirmed histologically after the experiments. Drug effects were expressed relatively to the potassium-induced contraction. Angiotensin II concentration-dependently contracted arteries and veins by maximally 1.66 +/- 0.31 N/m and 0.43 +/- 0.08 N/m, respectively (P < 0.05). In arteries the angiotensin II were subject to a mild degree of tachyphylaxis: the Emax of the repetitive concentration-response curve (CRC) was reduced from 105 +/- 4% of the potassium-induced contraction to 84 +/- 6% (P < 0.05); the EC50 value was unchanged (P > 0.05). In veins no tachyphylaxis was observed. Losartan caused a rightward shift of the CRC of angiotensin II in arteries and veins (P < 0.05), and reduced the Emax in arteries from 105 +/- 4 to 85 +/- 9% (P < 0.05), but did not change the Emax in veins. Nicardipine significantly decreased the Emax in arteries and veins (to residual values of 10 +/- 2 and 20 +/- 4%, respectively, of the control values). In conclusion, the angiotensin II-induced constriction of human arteries and veins isolated from mammary tissue are AT1-receptor mediated and inhibited by losartan. The nearly complete inhibition by nicardipine indicates that the constrictor effects in both types of vessels are dependent on L-type calcium channels.

Acetylcholine↗

Circadian variation of paroxysmal supraventricular tachycardia.

BACKGROUND: Various clinical manifestations of cardiovascular diseases have a pattern of circadian variation. In this study, we investigated whether the onset and duration of paroxysmal supraventricular tachycardia (PSVT) has a circadian variation. METHODS AND RESULTS: In our analysis, we included 105 patients with 498 PSVT episodes. In this study, the onset of PSVT did not have a uniform distribution throughout the 24-h period. There were nearly equal peaks in the time periods from 8:00 to 9:00 AM, 12:00 to 1:00 PM, and 5:00 to 6:00 PM, with a trough at night. The duration of PSVT also did not show a uniform distribution throughout the 24-h period; it increased significantly during the daytime, with a peak between 1:00 and 2:00 PM, another peak between 6:00 and 7:00 PM, and a significant reduction at night. CONCLUSIONS: The onset and duration of PSVT showed a circadian variation. However, the time-oriented antiarrhythmic therapy for preventing PSVT needs further study.

Adult↗