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Biomedical subjects

S G Yang

Publications and source records attributed to S G Yang.

At least 19 recordsLinked to original sources

Stable bioavailability of cyclosporin A, regardless of food intake, from soft gelatin capsules containing a new self-nanoemulsifying formulation.

AIM: We recently succeeded in preparing soft gelatin capsules containing a new self-nanoemulsifying formulation consisting of cyclosporin A (CsA), triacetin, polyoxyl 40 hydrogenated castor oil, polysorbate 20, medium chain triglycerides and medium chain mono- and diglycerides. The soft capsules containing the new formulation exhibited a significantly improved physical stability in terms of the appearance of the gelatin capsule shells and the composition of the fill mass during long-term storage, compared to commercially available soft capsules containing CsA, in which ethanol was employed as a cosolvent of CsA. In the present study, the influence of a fat-rich meal on the bioavailability of CsA from the soft capsule containing the new formulation (test drug) was evaluated and the results compared to those obtained with a representative soft capsule of CsA. VOLUNTEERS AND METHODS: A randomized, open-label, 3-way crossover study was performed in the test capsules and reference soft capsules, in a fasted state or after a fat-rich breakfast. 18 healthy male volunteers received a single dose of the reference formulation (Neoral, Novartis AG, Basel, Switzerland) or test formulation (2 capsules each, 200 mg as CsA) with 240 ml of water with a 1-week washout period between the treatments, after a fat-rich (670 kcal, 45 g fat) breakfast (for the test drug, Treatment A; for the reference drug, Treatment B) or a 12-h fasting (for the test drug, Treatment C). Serial blood samples, collected over a 24-h period after the administration, were assayed for blood CsA concentrations using a specific monoclonal radioimmunoassay. RESULTS: The differences in bioavailability parameters (i.e., AUC(0-24h), AUC(0-infinity) and C(max)) between the treatments were within the range of 80-125% of the reference treatment. An analysis of variance (ANOVA) revealed no significant differences (p > 0.05) between subjects, formulations or periods. The 90% confidence intervals (CI) indicated that the differences between the treatments (Treatments A and B, Treatments A and C) were also within the criteria. CONCLUSION: These results indicate that the bioavailability of CsA from the test drug is equivalent to reference in the fed state, and is likely to be less influenced by a fat-rich meal. Therefore, the new formulation of CsA using triacetin appears to have an advantage over the commercial soft capsules of CsA using a volatile cosolvent such as ethanol.

Administration, Oral↗

Preparation and characterization of straight and zigzag AlN nanowires.

Hexagonal single-crystal AlN nanowires with straight or zigzag morphologies were successfully synthesized by the reaction of aluminum alloy in an ammonia/nitrogen atmosphere at 1100 degrees C. It is found that the crystal tropism of the nanowires is along [0001], whereas the growth directions of the zigzag nanowires shift between [2111] and [2111].

Letter↗

A new selection method for pepper transformation: callus-mediated shoot formation.

We used two genes, TMV-CP and PPI1 (pepper-PMMV interaction 1 transcription factor), to transform commercially important chili pepper (Capsicum annuum) inbred lines (P915, P409) by means of Agrobacterium co-culture. Eighteen independently transformed T0 plants were obtained. The most critical point in the pepper transformation protocol was the selection of shoots growing on calli--referred to as callus-mediated shoot formation (indirect shooting)--because shoots not grown from the callus (direct shooting from the wounded surface) developed into non-transformants. Selection of the correct right callus type also proved to be an important requirement for obtaining transformed peppers. Six different types of callus developed during the selection process. Shoots regenerated from two of these types, while one type regenerated significantly more shoots than the other types, suggesting that the capacity for shoot formation is callus type-specific. Although the transformation rate was low, transformation via callus-mediated shoot formation proved to be reproducible and was confirmed by Southern and Northern blot analyses. Based on the experimental data, we have succeeded in developing a new protocol for the selection and transformation of pepper and expect that it will be used in the future for pepper transformation.

Capsicum↗

Once-a-day oral dosing regimen of cyclosporin A: combined therapy of cyclosporin A premicroemulsion concentrates and enteric coated solid-state premicroemulsion concentrates.

PURPOSE: To develop once-a-day oral dosing regimen that provides the blood levels of cyclosporin A (CsA) in the therapeutic ranges over 24 hours. METHODS: CsA premicroemulsion concentrates (preME) were formulated from phase diagrams. Enteric-coated solid-state premicroemulsion concentrates (sME) were prepared by coating preME with enteric-coating matrials and solidifying them. CsA was measured using high-performance liquid chromatography or radioimmunoassay. RESULTS: PreME consisted of CsA, oil, and mixture of surfactants and a cosurfactant. PreME spontaneously formed microemulsions in aqueous medium and showed oral absorption profiles similar to Sandimmune Neoral in dogs. Dispersion of sME in aqueous medium also formed microemulsions. Release rates of CsA from sME depended on pH and the type of enteric-coating materials and highly correlated with the extent of oral absorption. The co-administration of preME and sME (200 mg CsA) showed the maximum blood level of CsA not significantly different from that of preME (100 mg CsA) and the concentration of CsA close to the minimum therapeutic level at 24 hours. CONCLUSIONS: The combined treatment of preME and sME provided controlled oral absorption of CsA over a 24-hour period. Such once-a-day dosing regimens will lead to increased patient compliance and reduced episodes of organ rejection after transplantation.

Administration, Oral↗

Recurrent arch obstruction after repair of isolated coarctation of the aorta in neonates and young infants: is low weight a risk factor?

BACKGROUND: Repair of aortic coarctation is often delayed in small infants because of the belief that such patients are at risk of recurrent arch obstruction and that growth will decrease this risk. To determine whether low weight was a risk factor for recurrent arch obstruction, we reviewed our experience with coarctation repair via left thoracotomy in infants less than 3 months of age. METHODS: From 1990 to 1999, 103 patients less than 3 months of age underwent repair of aortic coarctation through a left thoracotomy. Median age was 18 days (1-90 days), with 45 patients less than 2 weeks. Median weight was 3.3 kg (1.0-6.4 kg) and 14 patients were less than 2 kg. The method of repair was resection and end-to-end anastomosis in 64 patients, subclavian flap angioplasty in 34, and patch augmentation of the arch in 5. Demographic, echocardiographic, and operative variables were analyzed for correlation with recurrent arch obstruction. RESULTS: One early and 1 late death occurred, both in patients who had complications but no evidence of recoarctation. At median follow-up of 24 months, reinterventions for recurrent arch obstruction were performed in 15 patients. The median time to reintervention was 5 months and was less than 1 year in 12 patients. Kaplan-Meier freedom from arch reintervention was 88% at 1 year (95% confidence intervals: 82%-94%) and 82% at 5 years (95% confidence intervals: 72%-92%). Factors associated with shorter duration to arch reintervention by univariable Cox regression included younger age (continuous, P =.01; <2 weeks, P =.005), smaller transverse arch (absolute diameter, P <.001; indexed to weight, P =.03; indexed to ascending aortic diameter, P =.02), and smaller ascending aorta (absolute diameter, P =.02). Smaller absolute transverse arch diameter and younger age were the only independent predictors of shorter time to arch reintervention by multivariable Cox regression analysis. Weight and type of repair did not correlate with risk of recoarctation. CONCLUSIONS: Low weight is not a risk factor for recurrent obstruction after repair of coarctation of the aorta in infants less than 3 months of age. Rather, risk of recoarctation is more a function of the anatomy of the arch. Thus, it is not indicated to delay repair in low weight infants with the goal of achieving growth.

Aortic Arch Syndromes↗

[Improvement of amplification method for Cryptosporidium parvum oocysts from mice].

OBJECTIVE: To establish a simplified amplification method for obtaining a large number of purified Cryptosporidium parvum oocysts from infected C57BL/6N mice. METHODS: All mice in the experimental groups were immunosuppressed by given different concentrations of dexamethasone phosphate added in drinking water throughout the experiment. The recovery and purity of the oocysts obtained using different purification methods was compared. The infectivity of the oocysts obtained from the same origin but different animals and different purification methods in a bovine fallopian tube epithelial cell culture system was studied. RESULTS: 4.16 x 10(9) oocysts were obtained in 30 mice in the 3rd group with dexamethasone of 20 micrograms/ml in drinking water. No significant difference in the oocyst recovery, purity and infectivity was found between methods using saturated saline floatation and sucrose density gradient centrifugation. The infectivity of the oocysts obtained from the same origin but different animals was similar. CONCLUSION: A simplified amplification method for obtaining a large number of purified Cryptosporidium parvum oocysts from the infected mice was established.

Animals↗

Evaluation of ventricular septal defect repair using intraoperative transesophageal echocardiography: frequency and significance of residual defects in infants and children.

Intraoperative transesophageal echocardiography (IOTEE) is commonly used to assess for residual defect and the need to return to bypass after repair of ventricular septal defect (VSD). The frequency and significance of residual septal defects as noted on IOTEE has not been well defined. We evaluated the frequency of residual VSD via IOTEE and the relationship between size of a residual VSD and rate of reoperation. In addition, we looked at the relationship between the presence of a residual VSD via IOTEE and the presence of residual VSD at follow-up transthoracic echocardiography (TTE). Residual VSD was measured via the largest width of the Doppler color jet diameter originating at the left ventricular septal surface. Of the 294 patients evaluated with IOTEE after VSD repair, one-third had a residual defect by IOTEE Doppler color flow mapping. Two-thirds of these defects closed spontaneously on TTE by the time of hospital discharge. There was no difference in frequency of residual VSD between simple (VSD closure alone, n = 90) and complex (VSD with associated lesions, n = 204) repair. Return to bypass with immediate reoperation was undertaken in nine patients, all of whom had significant shunt via oximetry (Qp/Qs > 1.5:1.0). All had residual VSD color jet diameters > 3 mm. Seven patients had residual color jet equal to 3 mm; however, hemodynamic studies did not reveal a significant shunt and none of these had reoperation. Seven patients with no VSD or < 3 mm residual VSD via had late reoperation to close residual VSD at 4 days to 5 months after initial operation. These were due to patch dehiscence or development of an "intramural" VSD in patients with conotruncal anomaly. A residual defect on IOTEE color Doppler measuring > or = 4 mm predicts the need for immediate reoperation, while a 3 mm defect may be significant and requires additional intraoperative hemodynamic evaluation. The majority of small defects noted on IOTEE are not present at discharge TTE. Patients with conotruncal defect repair should be followed closely for development of late significant "intramural" defects.

Age Factors↗

Clear cell acanthoma presenting as polypoid papule combined with melanocytic nevus.

We report on a case of clear cell acanthoma that developed above a preexisting melanocytic nevus. Although melanocytic nevi can be complicated by the presence of several different types of epithelial or appendageal tumors, there have been no reported case of clear cell acanthoma combined with a nevus. Interestingly, in this case the clear cell acanthoma had a polypoid configuration, an unusual finding.

Adult↗

A case of glomeruloid hemangioma associated with multicentric Castleman's disease.

Glomeruloid hemangioma is a term that was coined J.K.C. Chan and colleagues in 1990 because the condition is histopathologically similar to renal glomeruli. In the three cases described to date, there have been signs of POEMS syndrome of multicentric Castleman's disease. We present the case of a 44-year-old Korean woman who developed glomeruloid hemangioma in association with multicentric Castleman's disease and some features of POEMS syndrome. It is interesting that in this patient, the first biopsy specimen revealed an immature vascular tumor that could not be precisely classified and the second indicated glomeruloid hemangioma. The present case may lend support to the suggestion that in POEMS disease, some types of vascular proliferations develop in response to angiogenic stimuli that show a spectrum of histopathologic features, and glomeruloid hemangioma is one of the reactive vascular proliferations. We believe that the primitive vascular tumor seen in the first biopsy specimen may be the most immature stage of this spectrum.

Adult↗

Malignant proliferating trichilemmal tumor showing distant metastases.

We describe a case of malignant proliferating trichilemmal tumor showing multiple distant metastases. For 10 years, the patient had had a round mass in the occiput, which recurred twice after wide excisions, and later metastasized to the cervical lymph nodes, periparotid area, and chest. Each time the lesions were excised, histologic specimens demonstrated a proliferating trichilemmal tumor with increasing nuclear atypia. Serial specimens showed increasing Ki-67 positivity as the extent of the tumor advanced.

Adult↗

Inflammatory nodules of the lower legs: a clinical and histological analysis of 134 cases in Korea.

We analysed 134 Korean cases with inflammatory nodules of the lower legs on the basis of clinicopathological findings, responsiveness to various therapeutic agents, and clinical course. There were 53 cases of erythema induratum (EI), 18 of erythema nodosum (EN), 40 of EN-like lesions of Behcet's disease, 15 of other entities, including superficial migratory thrombophlebitis, cutaneous periarteritis nodosa, sarcoidosis, malignant lymphoma, Churg-Strauss syndrome, and parasitosis, and eight unclassified cases. The unclassified group was composed of a spectrum of diseases with clinicopathologic features ranging between those typical of EN and EI. The present study revealed that the profiles of diseases featuring inflammatory nodules of the lower legs in Korea differed from those found in other areas. These geographic and demographic differences should be kept in mind when managing a patient with inflammatory nodules of the lower legs.

Adolescent↗

Epstein-Barr virus-associated lymphoproliferative eruption with progression to large granular lymphocytic leukaemia.

A 12-year-old Korean girl gave a 9-year history of recurrent necrotizing papules and vesicles on the face, scalp and extremities. Skin biopsy specimens showed an atypical lymphoreticular infiltrate with vasculitis in the dermis and subcutis. In situ hybridization demonstrated latent infection by Epstein-Barr virus (EBV) of the lymphoid cells in the dermis. The disease was diagnosed as an EBV-associated lymphoproliferative skin eruption presenting as recurrent necrotic papulovesicles. The patient subsequently developed large granular lymphocytic leukaemia of natural killer cell origin. Our observations suggest that a patient with an EBV-associated lymphoproliferative skin eruption presenting with recurrent necrotic papulovesicles might progress to develop leukaemia as well as lymphoma.

Child↗

Tyrosine kinase inhibitors and the contractile action of G-protein-linked vascular agonists.

In a porcine coronary artery helical strip preparation, the tyrosine kinase inhibitors genistein and tyrphostin (AG82) attenuated the contractile actions of angiotensin II, arginine vasopressin, epidermal growth factor--urogastrone, noradrenaline, and prostaglandin F2 alpha, under conditions where contractions due to acetylcholine and KCl were not affected. Both genistein and tyrphostin also caused a selective inhibition of angiotensin II action in rat aorta helical strips, without affecting KCl-mediated contractions. The IC50 values for the inhibition of contraction in the porcine coronary artery were in the range of 2-5 microM for genistein and 8-15 microM for tyrphostin. Comparable IC50 values were observed for the inhibitory effects of genistein on angiotensin II and prostaglandin F2 alpha action in the rat aorta, whereas much higher tyrphostin concentrations (IC50 > or = 40 microM) were required to block angiotensin II action in this preparation. Angiotensin II caused an elevation of phosphotyrosyl protein (antiphosphotyrosine Western blot) in the porcine coronary artery, which was reversed by genistein. In addition, porcine coronary artery derived membrane and cytosolic fractions exhibited sarcoma virus related tyrosine kinase activity, which was inhibited by both genistein and tyrphostin. Our data (i) document the selective inhibition by genistein and tyrphostin of the contractile action of some, but by no means all, G-protein-linked vascular agonists in porcine and rat arterial preparations, (ii) establish the presence of sarcoma virus related tyrosine kinase activity in the porcine coronary artery, and (iii) demonstrate angiotensin II mediated increases in phosphotyrosyl protein content in porcine coronary artery tissue. These data support the hypothesis that selected G-protein-linked contractile vascular agonists may act in part via the stimulation of nonreceptor tyrosine kinases. The data also indicate the complex actions of the tyrosine kinase inhibitors, even for the same agonist acting in vascular preparations obtained from different species.

Animals↗

Ligand binding characterization and molecular analysis of distinct epidermal growth factor-urogastrone receptors in cultured smooth muscle and epithelial cells from guinea pig intestine.

In parallel, we measured the receptor binding affinities for epidermal growth factor-urogastrone (EGF-URO) and transforming growth factor-alpha (TGF-alpha) in cultured smooth muscle (GCM) and epithelial (GPC) cells derived from guinea pig intestine. The relative order of binding affinities in the GCM cells was TGF-alpha > EGF-URO, in keeping with the relative order of biological potencies of these polypeptides in a guinea pig gastric circular muscle contractile bioassay. These data established by ligand binding criteria the presence of a TGF-alpha-preferring receptor in the guinea pig. In contrast, there was a reversed order of binding affinities (EGF-URO > TGF-alpha) for the polypeptides in GPC cells, in accord with an identical order of bioassay potencies previously observed in a guinea pig gastric longitudinal muscle contractile bioassay. Using a reverse transcription-polymerase chain reaction approach, we also cloned and sequenced putative EGF-URO receptor ligand binding domain III from each cell type. Although the binding specificity for TGF-alpha and EGF-URO differed in the GCM and GPC cells, the amino acid sequences of receptor domain III were identical in the two cell types. We conclude that the previously measured differences in biological potencies of EGF-URO and TGF-alpha in the contractile bioassay preparations are due to the distinct receptor binding affinities of EGF-URO and TGF-alpha that can be detected in different tissues. However, our data document that the distinct relative binding affinities for EGF-URO and TGF-alpha that can be observed in different cell types from the same species cannot be accounted for solely by the sequence of putative receptor ligand binding domain III.

Animals↗

Distinct signal transduction pathways for angiotensin-II in guinea pig gastric smooth muscle: differential blockade by indomethacin and tyrosine kinase inhibitors.

In guinea pig gastric longitudinal (LM) and circular (CM) muscle strips, angiotensin-II (Ang-II) caused a concentration-dependent contraction that required extracellular calcium and that could not be attributed to the secondary release of agonists from neural elements. Contractions in both the LM and CM were blocked by the Ang-II AT1 receptor antagonist, Losartan (DuP 753, pA2 9.1) but not by the AT2 antagonist, PD 123319. However, in the LM preparation, indomethacin (3 microM) blocked Ang-II-mediated contraction, whereas in the CM contraction was resistant to indomethacin. Contractions caused by Ang-II in the CM preparations were also unaffected by inhibitors of leukotriene biosynthesis, but were partially (58%) inhibited by the cytochrome P450 monooxygenase inhibitor, ketoconazole. The diacylglycerol lipase inhibitor, U57,908, at a concentration (20 microM) that completely blocked the contractile action of epidermal growth factor in the LM, caused a substantial inhibition of Ang-II-mediated contraction in both the LM (55% inhibition) and CM (75% inhibition). The phospholipase A2 inhibitor, mepacrine caused a modest inhibition (24%) of contraction in both preparations. In the presence of U57,908, mepacrine further inhibited contraction caused by Ang-II in the LM preparation. The tyrosine kinase (YK) inhibitors, genistein and tyrphostin (RG 50864) selectively and completely blocked Ang-II-mediated contraction in the LM, without affecting contractions caused by carbachol and bradykinin. In the CM preparation, the two YK inhibitors were selective, but only partially (40-60%) blocked Ang-II-mediated contraction, without affecting contractions caused by bradykinin and carbachol.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗