Prostaglandin E1 and dibutyryl cyclic AMP enhance platelet resistance to deformation

The effect of prostaglandin E₁ (PGE₁) on platelets is mediated through the PGE₁ receptor and the consequent maintenance of the platelet's discoid shape. The effects of PGE₁ and dibutyryl cAMP (dbcAMP) on the deformability of human platelets were studied. Deformability tests based upon the micropipette aspiration on the platelets were performed by using pipettes with radii (Rp) of 0.26-0.36 gm. The time course of the extension length (Dp, in μg) of the platelets in response to aspiration with a negative pressure (ΔP) of 5 cm H₂ O (ΔP × Rp = 0.15 dynes/cm) was analyzed. PGE₁ treatment (0.1 μM) resulted in a decrease of platelet deformability as compared with results obtained for apparently non-activated, control platelets. The deformation index, i.e., Dp/Rp (PGE₁ -treated) / Dp/Rp (control), was significantly reduced to 0.90 ± 0.04. DbcAMP treatment also significantly decreased the deformability of platelets and this decrease was dbcAMP dose dependent. In contrast, colchicine- or cytochalasin D-treated platelets increased deformability. PGE₁ -treated platelets had a higher [cAMP]_i than controls. Platelets treated with PGE₁ or dbcAMP showed a reduced [Ca²⁺]i increment induced by thrombin as compared to non-treated controls. These results indicate that PGE₁ and dbcAMP treatment of platelets is accompanied by an enhancement of platelet resistance to deformation. The increased [cAMP]_i and low [Ca²⁺]_i after PGE₁ treatment may limit the rearrangement of cytoskeleton and thus enhance platelet resistance to deformation.     

Pharmacokinetics of oral alminoprofen (Minalfen) in elderly patients with rheumatoid arthritis and spondylosis deformans]

The pharmacokinetics of oral Alminoprofen, a nonsteroidal anti-inflammatory drug, were studied in five elderly patients with rheumatoid arthritis and spondylosis deformans after 200 mg (three times a day) repeated dose for 5 days. The pharmacokinetic parameters after oral administration of Alminoprofen were analyzed by the one-compartment open model method. The maximum plasma concentrations (Cmax) were 16.1 +/- 2.5 micrograms/ml, after dosing on day 1, 25.2 +/- 1.6 micrograms/ml on day 3 and 21.6 +/- 2.7 micrograms/ml on day 5. The maximum time (Tmax) were about 2 hours after the medication in al cases. The area under the curve in drug concentration in plasma versus time (AUC) were 58.5 +/- 6.3 micrograms hr/ml on day 1, 58.5 +/- 3.1 micrograms hr/ml on day 3 and 58.1 +/- 8.5 micrograms hr/ml on day 5. The biological half-lives (t1/2) were 2.45 +/- 0.35, 2.09 +/- 0.82 and 2.49 +/- 0.63 hours, after dosing on day 1, day 3 and day 5, respectively. The analysis of moment in pharmacokinetics revealed that the mean residence time (MRT) on day 1, day 3 and day 5 observed were 2.31 +/- 0.03, 2.15 +/- 0.09 and 2.15 +/- 0.07 hours, respectively. The variance residence times (VRT) observed were 0.95 +/- 0.05 hour2 on day 1, 0.88 +/- 0.09 hour2 on day 3 and 1.06 +/- 0.07 hour2 on day 5. The ratios of accumulation calculated were 1.16 +/- 0.05 in both the morning medication on day 3 day 5, and it therefore appears that the steady-state equilibrium is established within 3 days after commencement of dosage.(ABSTRACT TRUNCATED AT 250 WORDS)     

Surgical repair of total anomalous pulmonary venous connection in neonates and infants--prevention for pulmonary venous obstruction at the site of anastomosis

From October, 1980, to June, 1987, thirty-eight infants less than one year old underwent correction for total anomalous pulmonary venous connection (TAPVC). Overall operative mortality and late mortality were 13% and 6%, respectively. Residual pulmonary hypertension was noted in 4 patients: three had pulmonary venous obstruction at the site of atrial anastomosis (PVOA) and one had supracardiac (Ia) lesion left after repair of mixed type (IV: Ia + III) of TAPVC. Two late deaths occurred in these with PVOA. Twenty-two patients with supracardiac (I) or infracardiac (III) TAPVC were divided into three groups according to the technical development in atrial anastomosis: the large anastomosis in which venous incision reached into at least one pulmonary vein beyond common pulmonary vein and the continuous running suture were used in 10 patients (group 1), the appropriate size of anastomosis in which venous incision limited within the common pulmonary vein and the continuous running suture used in 4 patients (group 2), and the appropriate size of anastomosis and the interrupted suture in 8 patients (group 3). PVOA were 3 (33%) in group 1, but 0 (0%) in group 2 and 3. Two late death occurred all in group 1 with PVOA. Cardiopulmonary bypass time and aortic clamp time in group 3 were 91 min and 74 min respectively, which did not become longer than those in both group 1 and group 2. Interrupted suture technique does not make operating time longer than continuous running suture one. PVOA is one of the important factors predicting late operative result.(ABSTRACT TRUNCATED AT 250 WORDS)     

Quantitative whole-body autoradiographic analysis of the tissue distribution of orally-administered [14C]cholesterol in hypercholesterolemic rats

The cholesterol-fed rat model has been used to examine the distribution of radiolabeled cholesterol by whole-body autoradiographic and quantitative videodensitometric methods. Animals were fed a hypercholesterolemic diet for 7 days, and were subsequently killed at 3, 6, 12, 24, or 72 h following a single oral dose of [14C]cholesterol. Maximum blood and tissue levels were observed at 12 h, while liver and adrenals were the most intensely labeled tissues. Liver maintained consistently high levels over the course of the study, while activity in other tissues declined moderately by 72 h, indicating the long half-life of cholesterol radioequivalents in tissue. The results of these experiments suggest that autoradiographic examination of cholesterol distribution in animals treated with pharmaceutical agents designed to modify cholesterol absorption or clearance will be useful in providing supplemental or confirmatory information on the drugs' mode of action.     

Malignant melanoma metastatic to the stomach: upper G-I endoscopic finding--report of a case

a 54-year-old male was presented with huge, black, ulcerative and painless tumor of the sole of left foot. Malignant melanoma was proved by biopsy, but patient refused any treatment. He visited our hospital again when bloody vomitus was noted two months later. Chest P-A revealed multiple lung metastases, and marked liver metastasis was also found by abdominal echo. Upper gastrointestinal (UGI) panendoscopy revealed multiple melanotic nodules with ulcerations at the tip, scattering diffusely on the fundus and upper body of the stomach. Metastatic malignant melanoma was proved by endoscopic biopsy. Metastatic tumor of the stomach was rare, and the endoscopic finding of the malignant melanoma with gastric metastasis was more rarer in the literature in Taiwan. So we would like to present the very rare finding of the endoscopy.     

Pancreas divisum with early pancreatic cancer--presenting as chronic obstructive pancreatitis.

A 61-year-old man experienced four bouts of pancreatitis in 1 year. Detailed history taking and a series of examinations, including sonography, computed tomography scan, and endoscopic retrograde cholangiopancreatography (ERCP), revealed pancreas divisum on the first admission. He was treated conservatively. However, repeated ERCP on the fourth admission, 1 year later, showed a small filling defect in the tail of the pancreatic duct. A distal pancreatectomy was carried out. Pathological studies revealed a small papillary adenocarcinoma (1.5 x 1.0 x 0.5 cm) confined to the pancreatic duct grossly with minimal parenchymal invasion microscopically. He has been free from cancer and pancreatitis for 13 months since the operation.     

Serum gastrin levels in children with peptic ulcer disease.

Fasting serum gastrin values were measured by radioimmunoassay in 53 children with peptic ulcer disease. The mean fasting serum gastrin levels for children with chronic duodenal ulcer, acute gastric ulcer, acute duodenal ulcer who were younger than two years old and acute duodenal ulcer who were older than two years old were: 46.2 +/- 25.7 pg/mL, 46.9 +/- 43.5 pg/mL, 47.9 +/- 12.0 pg/mL and 37.5 +/- 17.8 pg/mL, respectively. Children with peptic ulcer disease did not have elevated fasting serum gastrin levels when compared with age-matched controls. We conclude that a fasting serum gastrin value cannot be used as a screening test for peptic ulcer disease in children, except for Zollinger-Ellison syndrome.     

The role of endothelin-1 during ischemia-reperfusion injury.

In order to investigate the role of endothelin-1 during ischemia-reperfusion injury, 80 adult male Wistar rats were subjected to three hours of ischemia and one hour of reperfusion. Animals were evenly divided into eight groups. The rats in group 1 served as the normal control group, while the rats in group 2 received an intravenous infusion of endothelin-1 in a dosage of 0.5 ng/kg/min, group 3 in a dosage of 5 ng/kg/min, and group 4 in a dosage of 50 ng/kg/min. The rats in group 5 were infused with angiotensin II (10 ng/kg/min). The rats in group 6 received an intravenous infusion of 10,000 units of superoxide dismutase and 10,000 units of catalase. Group 7 rats were infused with endothelin-1 (50 ng/kg/min), superoxide dismutase (10,000 units), and catalase (10,000 units). Group 8 rats received an infusion of angiotensin II (10 ng/kg/min), superoxide dismutase (10,000 units) and catalase (10,000 units). The infusions were given during the reperfusion period. After one hour of reperfusion, the gastrocnemius and soleus muscles of the experimental animals were excised and assayed for ischemia-reperfusion injury by measuring triphenyltetrazolium chloride (TTC) reduction. The results showed that the limb activity of the ischemic extremity was 40.33 +/- 2.75% in group 1, 41.62 +/- 4.08% in group 2, 14.42 +/- 3.14% in group 3, 4.43 +/- 1.05% in group 4, 23.81 +/- 3.51% in group 5, 57.23 +/- 4.52% in group 6, 31.79 42- 3.63% in group 7, and 27.39 +/- 3.95% in group 8. Endothelin-1 reduced the limb activity in a dose-dependent manner.(ABSTRACT TRUNCATED AT 250 WORDS)