Mechanism for Drug Absorption from Rat-liver Surface Membrane: Effect of Dose and Transport Inhibitors on the Pharmacokinetics of Phenol Red

We examined the effect of dose and transport inhibitors on the pharmacokinetics of phenol red as a model drug after application to rat liver surface in-vivo, employing a cylindrical glass cell (i.d. 9 mm, area 0·64 cm²), to elucidate the mechanism for drug absorption from liver surface membrane. Absorption ratios of phenol red in 6 h were determined to be 91·1, 91·8 and 89·9% at a dose of 0·3, 1 and 3 mg, respectively. The AUC value for plasma concentration profile of phenol red was proportional to the dose. It is thus suggested that the absorption process of phenol red from rat liver surface does not approach saturability. The time course of the remaining amount of phenol red in the glass cell obeyed first-order kinetics at a dose of 0·3 mg, and its rate constant K_a was calculated to be 0·0069 min^?1. Moreover, no significant difference was seen in the K_a value within the dose range of 0·3-3 mg, which was estimated by curve fitting of the plasma concentration profile of phenol red after application to rat liver surface in the two-compartment model with first-order absorption. 2,4-Dinitrophenol (0·3 mg) and probenecid (0·5 and 1 mg), inhibitors of metabolic energy and anion transport, respectively, had no significant effect on the pharmacokinetics of phenol red after application to rat liver surface. These data demonstrate that a specific transport mechanism such as active transport is not involved in phenol red absorption from rat liver surface membrane.     

Case report: Portal-systemic encephalopathy due to a congenital extrahepatic portosystemic shunt

We present a case of portal-systemic encephalopathy due to a congenital splenorenal shunt. A 69 year old woman was admitted to hospital because of recurrent episodes of disturbed consciousness. The present episode had begun 3 months prior to admission. Although the patient demonstrated mildly slurred speech, the remainder of her neurological examination was unremarkable. She showed no clinical signs of portal hypertension and her liver function, except for a serum hepaplastin test of 58% and an ICG retention rate of 28% at 15 min, was normal. Her serum ammonium level was 210 μg/dL. The venous phase of a superior mesenteric arteriogram revealed a splenorenal shunt and narrowing of the portal vein, which was 4 mm in diameter. The histological findings, demonstrated by a needle liver biopsy specimen, were consistent with mild fibrosis and lymphocytic infiltration. Following the diagnosis of a splenorenal shunt in the absence of liver cirrhosis, ligature of the shunt was performed with a splenectomy. The portal vein pressure after ligature of the shunt rose from 12.5 to 18.8 mmHg. This shunt was thought to be of congenital origin. The high preoperative serum ammonia concentration decreased to the normal range postoperatively and the serum hepaplastin test and ICG retention rate similarly improved postoperatively. A follow-up superior mesenteric arteriogram was performed during the venous phase, demonstrating resolution of the shunt and decreased portal vein narrowing. The patient has suffered no further episodes of disturbed consciousness postoperatively.     

Impact of sociodemographic and diabetes-related characteristics on depressive state among non-insulin-dependent diabetic patients

Abstract  One hundred and fifty-one non-insulin-dependent diabetic patients were assessed to detect sociodemographic, psychological and disease-related characteristics that were related to depressive state among diabetic patients. Depressive state in the patients was correlated with poor social support and low economic status, premorbid neurotic personality and the presence of complications, retinopathy in particular. However, depressive state did not correlate with age, gender, education, serum level of HbA_1C or duration of diabetes. The severity of the depressive state in diabetic patients may vary with the cultural background of the patient and/or the country in which he or she is living. In treating diabetic patients, doctors need to pay special attention to these factors.     

Morphological Variation of Nonreentrant Idiopathic Ventricular Tachycardia Originating from the Right Ventricular Outflow Tract and Effect of Radiofrequency Lesion

RF catheter ablation was performed in 16 patients with nonreentrant idiopathic VT originating from the RVOT. All documented VT was monomorphic, but subtle morphological variation in the VT-QRS complex was observed in 10 (63%) of 16 patients. Through endocardial mapping, VT origin was determined within a narrow site (< 0.5 ± 0.5 cm) in 4 of the 10 patients with the morphological variation. In the other 6 of 10 patients, the origin extended to an area of > 0.5 ± 0.5 cm. In VT with morphological variation, the local electrogram at the site of VT origin also showed variation in morphology and activation sequence. For VT of narrow origin, RF application to the site eliminated the VT. However, in VT from a wide arrhythmogenic area, RF current had to be delivered to 3–7 distinct sites to cover the possible origin, and specific QRS configuration of VT and/or PVC was ablated at each of the earliest activation site. All but one VT were successfully ablated by RF current. Subtle morphological variation was frequent in this type of VT, and about half were associated with a wide arrhythmogenic area. Precise mapping and analysis of the efficacy of each BF application might be helpful to better understand the relationship between subtle changes of VT-QRS morphology and their origins.     

Phase I and Preliminary Phase II Studies on Aclacinomycin A in Patients with Acute Leukemia

Eight patients with acute nonlymphocytic leukemia (ANLL) andfive patients with acute lymphocytic leukemia were treated withaclacinomycin A. It was given daily by one-hour infusion indoses ranging from 0.33 to 0.70 mg/kg for seven to 20 days withoutother antileukemic agents. Two patients with ANLL achieved completeremission and one with ANLL achieved partial remission. Itsmajor toxic effects were myelosuppression and gastrointestinalsymptoms.     

TREATMENT OF PATIENTS WITH RETROGRADE EJACULATION IN THE ERA OF MODERN ASSISTED REPRODUCTION TECHNOLOGY

Purpose

We determined a rational strategy for treatment of patients with retrograde ejaculation in the era of modern assisted reproduction technology.

Materials and Methods

In 7 consecutive patients medical treatment or retrieval of spermatozoa from the bladder was performed at a male infertility clinic.

Results

Antegrade ejaculation was restored in 3 patients, and spermatozoa were retrieved from the bladder and used for assisted reproduction in 3. Spermatozoa with good oolemma penetrating ability were collected by seminal vesicle massage.

Conclusions

Modern assisted reproduction technology is a powerful treatment option for retrograde ejaculation when combined with a technique to retrieve spermatozoa of good quality from the bladder.     

DETERMINATIONS OF ETHANOL, ACETALDEHYDE AND ACETATE IN BLOOD AND URINE DURING ALCOHOL OXIDATION IN MAN

Blood and urine samples were analyzed for ethanol, acetaldehydeand acetate during alcohol oxidation in Japanese men by headspace gas chromatography, following the consumption of 16 ml/kgof beer during a 20 min period. The maximum level of blood/urineethanol was found to be 15–17 mM (20–22 mM), whilethat of acetaldehyde in a flusher and in non-flushers was 20µM (52 µM) and 2–5 µM (10–13 µM),respectively. Acetate levels in these groups ranged from 0.2mM (0.1 mM) to 0.8 mM (1.0 mM). Blood ethanol levels were dosedependent, whereas acetaldehyde and acetate levels reflectedindividual metabolic rates. The relative concentrations of ethanoland acetaldehyde in blood and that of acetate in alcohol metabolismcould be summarized as follows: 7500 (15 mM): 1–3 (2–5µM); 250–400 (0.5–0.8 mM) for non-flushers;and 7500 (15 mM): 5–10 (10–20 µM): 250–400(0.5–0.8 mM) for a flusher.