Bioavailability of Bropirimine 250 mg Tablet in Dogs: Effect of Food

The postprandial effect on the bioavailability of bropirimine in dogs after oral administration of bropirimine tablets (Bropirimine 250 mg Tablet) was investigated. At a dose of 500 mg bropirimine (two tablets of bropirimine 250 mg), the maximum plasma concentration under the postprandial condition was about twice that observed under the fasting condition, and the area under the plasma concentration vs time curve under the postprandial condition was also twice that under the fasting condition. The absolute oral bioavailabilities of bropirimine were 41.1% under the fasting condition and 83.5% under the postprandial condition. It is considered that the longer gastric residence time and larger volume of the gastric fluid induced by food-intake caused the increase in dissolution of bropirimine which increased the bioavailability after oral dosing of bropirimine 250-mg tablets.     

Incidence and growth pattern of simple cysts of the kidney in patients with asymptomatic microscopic hematuria

BACKGROUND: We examined the incidence and natural history of simple renal cysts found by ultrasonography (US) in patients referred for asymptomatic microscopic hematuria. METHODS: Among the 906 patients aged 18-78 years, 743 patients who had undergone US were included in the present study. The natural history of simple renal cysts was investigated in 55 patients who underwent periodical US examinations for more than 3 years. RESULTS: The incidence of simple renal cysts was 4.3% for ages 29 years or younger, 15.3% for ages 30-39, 21.8% for ages 40-49, 23.3% for ages 50-59 and 32.6% for ages 60 years or older; thus the incidence increased in older age groups (P = 0.0005 for men, P = 0.0020 for women). Men tended to have a higher incidence than women. The degree of hematuria did not influence the incidence of renal cysts (P = 0.9044). The annual growth rate of the mean maximum diameter was 4.2% during a 3-year follow-up period in 55 patients and 5.1% during a 6-year follow-up in 31 patients. CONCLUSION: Since the diameter of a renal cyst may increase by 5% annually, the diameter of the cyst may increase by 1.6 times in 10 years. The scheduling of follow-up examinations depends on the size at the time of disclosure, the effects on calyceal systems, or the suspicion of a concurrent malignant disease. However, the most simple renal cysts may be followed-up at an interval of more than 10 years, once a diagnosis has been established.     

Characteristics of the antihistamine effect of TAK-427, a novel imidazopyridazine derivative

OBJECTIVE AND DESIGN: The characteristics of the antihistamine effect of the new antiallergic compound TAK-427 were investigated. MATERIALS AND METHODS: In vitro binding assay of [(3)H] pyrilamine was performed using recombinant human histamine H(1) receptors (rhH(1)R). In vivo studies were performed in male ICR mice or Hartley guinea pigs. Drugs were administered orally 1 h before examinations. Determinations were made of histamine-induced skin reaction, ex vivo measured radioligand binding to brain and lung H(1) receptors, pentobarbital-induced sleeping time, passive cutaneous anaphylaxis (PCA) reaction, and antigen-induced itch-scratch responses (ISRs). RESULTS: TAK-427 inhibited ligand binding to rhH(1)R with an IC(50) value of 17.3 nmol/l. TAK-427 inhibited histamine-induced skin reactions in guinea pigs and mice with an ID(50) value of 0.884 and 0.450 mg/kg, p.o., respectively; significant inhibition associated with 10 mg/kg of TAK-427 was still observed 24 h after dosing in guinea pigs. TAK-427 showed as high selectivity for peripheral H(1) receptors as terfenadine and epinastine did, which was evaluated by ex vivo measured radioligand binding. Even at 300 mg/kg, TAK-427 did not affect pentobarbital-induced sleeping time in mice. TAK-427 significantly inhibited PCA in mice and guinea pigs, and also inhibited antigen-induced ISRs in guinea pigs. CONCLUSIONS: These results suggest that TAK-427 may have a long-lasting antihistamine activity with minimum sedative side effect and suppress acute phase allergic reactions.     

Changes in Cell Characteristics Due to Culture Conditions in Cell Lines From Human Small Cell Lung Cancer

Eight cultured cell lines were established from human smallcell lung cancers. Every cell line showed the morphologicaland biochemical characteristics of small cell cancer. Changesin cell characteristics were observed in many of these celllines when culture conditions were changed: "oat cell type"changed to "intermediate cell type" and vice versa when serum-freemedium was changed to serum-supplemented medium; a deficiencyof vitamin A in the medium caused a change to squamous cellsand vice versa; and a tumor promoter (teleocidin B) enhancedthe adherence of these cells to the surface of plastic culturedishes. These findings provide evidence that many small celllung cancer cell lines can change their morphology with changesin the environment of the cells.     

Excretion Profiles of the Mycotoxin Deoxynivalenol, following Oral and Intravenous Administration to Sheep

Excretion Profiles of the Mycotoxin Deoxynivalenol, followingOral and Intravenous Administration to Sheep. PRELUSKY, D. B.,VEIRA, D. M., TRENHOLM, H. L., AND HARTIN, K. E. (1986). Fundam.Appl. Toxicol. 6, 356–363. The excretion profiles of deoxynivalenol(DON) and metabolites (DON glucuronide conjugate, 3,715-trihydroxytrichothec-9,12-diene-8-one(DOM-1), and DOM-1 glucuronide conjugate) were defined in malesheep following either intravenous (iv) or oral administrationof the toxin at levels of 0.5 and 5.0 mg DON/kg body wt, respectively.After iv dosing, urinary DON levels declined in a biphasic fashionwith an average elimination half-life (terminal phase) of 1.2hr. diminishing to baseline concentrations by 8 hr. Maximumurinary excretion rates for the two major metabolites identified(conjugated DON, conjugated DOM-1) occurred 0.5–1.5 hrafter dosing, exhibiting elimination half-lives of 2.2 and 3.1hr, respectively. Total recovery accounted for only about 66.5%of the dose: 63.0% in the urine (24.1% DON, 21.2% conjugatedDON, 0.5% DOM-1, 17.2% conjugated DOM-1) and 3.5% in bile (madeup almost completely of conjugated DOM-1). The peak biliaryexcretion rate for conjugated DOM-1 was found to occur within1 hr postdosing, which rapidly declined to baseline levels by5 hr. Following oral administration, urinary excretion ratesof the major metabolites (DON, conjugated DON, conjugated DOM-1)reached maximum 6–9 hr post-treatment, and declined exponentiallywith t values of 3.2, 4.0, and 5.0 hr, respectively. Urinaryand biliary recovery of administered DON averaged approximately7.1%: 7.0% in urine (2.1% DON, 3.6% conjugated DON, 0.06% DOM-1,1.2% conjugated DOM-1) and 0.11% in bile (predominately conjugatedDOM-1). Between 54 and 75% of the oral dose was recovered inthe feces. These findings indicate that DON and metabolitesdo not persist in the body following either a single oral orintravenous dose of DON and are rapidly excreted. However, followingiv administration, a portion of the dose (33.5%) remained unaccounted,presumably converted to unidentified metabolites. Based on theseresults it appears that metabolism is the major process of eliminationof DON in sheep.     

Is the Gauer-Henry reflex important for immersion diuresis in men?

BACKGROUND: This study examines the relationship between the threshold for plasma vasopressin concentration [PVP] responses and diuresis (Gauer-Henry reflex), and tests the hypothesis that water intake would not influence diuresis. METHODS: Eight men (19-25 yr) underwent four treatments: euhydration in air (Eu-air), euhydration in water immersion (Eu-H2O), and with prior 3.6% hypohydration in air (Hypo-air), and hypohydration in immersion (Hypo-H2O). Ad libitum drinking was allowed during the 3-h experimental and 1-h recovery periods. RESULTS: Drinking was greatest during the first 10 min: 3.5 ml x kg(-1) with Hypo-air (450 ml x 3 h(-1)) and only 1.7 ml x kg(-1) (p < 0.05) with Hypo-H2O (235 ml x 3 h(-1)). At 1 h, concomitant [PVP] decreased from a control level of 6.6+/-1.5 to 4.0+/-1 .0 pg x ml(-1) (delta = 2.6 pg x ml(-1), p < 0.05) with Hypo-air, and from 5.9+/-0.6 to 2.3+/-0.2 pg x ml(-1) (delta = 3.6 pg x ml(-1), p < 0.05) with Hypo-H2O. Urine flow was unchanged from control level (<1.0 ml x min(-1)) with Hypo-air, Hypo-H2O, and Eu-air, but increased to 4-5 ml x min(-1) with Eu-H2O. Neither water intake volume nor urine flow was related to the magnitude of [PVP] depression. Regression of Uosm/Posm ratio on [PVP] and urine flow indicated that [PVP] above 2 pg x ml(-1) did not affect urine flow. Thus, ad libitum water intake in previously hypohydrated subjects did not affect urine flow or the decrease in [PVP]. The threshold [PVP] to initiate significant diuresis was about 2 pg x ml(-1), and significant diuresis can occur with no change in [PVP] maintained at about 1 pg x ml(-1) during immersion in euhydrated subjects. CONCLUSIONS: Thus, it appears that the Gauer-Henry reflex is not the major mechanism for immersion-induced diuresis. Clearly, other diuretic factors are also involved.     

Type A aortic dissection involving a right-sided aortic arch

We report a rare case of a 39-year-old man with type A aortic dissection involving a right-sided aortic arch with the symptom of vascular ring. Computed tomography scanning and angiography were performed to define the extent of the dissection and the anatomy of the branching vessels. The ascending aorta was replaced through a median sternotomy and right thoracotomy using a hypothermic cardiopulmonary bypass associated with selective cerebral perfusion and partial circulatory arrest, and his symptom of vascular ring disappeared postoperatively.