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Biomedical subjects

Y Taki

Publications and source records attributed to Y Taki.

At least 19 recordsLinked to original sources

Torsion of a benign cyst arising from the tunica vaginalis testis.

We describe a rare case of torsion of a benign cyst originating from the parietal layer of tunica vaginalis. This case presented with acute scrotum. Surgical exploration revealed a cyst arising from the parietal layer of tunica vaginalis of which the pedicle was twisted. When a cystic mass is detected in the scrotum of boys with acute scrotum, torsion of a cyst in the cavum tunica vaginalis testis should be considered.

Child, Preschool↗

Nitric oxide induces a decrease in the mitochondrial membrane potential of peripheral blood lymphocytes, especially in natural killer cells.

Increased levels of nitric oxide (NO) at an inflammatory site may affect the biological activity of lymphoid cells. To investigate the effects of NO on the immune system, we measured the mitochondrial membrane potential (delta psi m) of the peripheral blood lymphocytes (PBL) cultured with a chemical NO donor. PBL from healthy volunteers were cultured with NOC18, a NO-generating compound, at various concentrations. The delta psi m of the PBL was measured by flow-cytometry using 3,3-dihexyloxacarbocyanine iodide (DiOC6(3)). NOC18 induced a decrease in the delta psi m of the PBL in a dose-dependent fashion, induced an increase in the levels of reactive oxygen species (ROS), and caused these cells to undergo apoptosis. Dual-color staining of the delta psi m and lymphocyte surface markers demonstrated that CD3-CD56+ natural killer (NK) cells were responsive to NO. Trolox, a vitamin E analog, partially reversed the NO-induced decrease in the delta psi m of the PBL. We showed that the delta psi m of peripheral NK cells were decreased by NO, which suggests that abundant NO at an inflammatory site may impair NK cell function.

Antioxidants↗

Dihydropyrimidine dehydrogenase activity and mRNA expression in advanced gastric cancer analyzed in relation to effectiveness of preoperative 5-fluorouracil-based chemotherapy.

Dihydroxypyrimidine dehydrogenase (DPD) is an enzyme involved in degradation and inactivation of 5-fluorouracil (5-FU). The amount of its expression in a tumor is thought to be a factor determining the response of the tumor to 5-FU therapy. We compared DPD activity and DPD mRNA expression in resected tumors between two groups of patients, i.e., a group of 14 patients with advanced gastric cancer who received preoperative chemotherapy (neoadjuvant chemotherapy; NAC) and surgery and a group of 24 patients with advanced gastric cancer who underwent surgery without preoperative chemotherapy. Tumor DPD activity was found to correlate well with tumor DPD mRNA expression. In the surgery alone group, DPD activity decreased significantly as the tumor stage advanced. This change was not observed in the NAC plus surgery group. Neither tumor depth (T factor) nor lymph node metastasis was found to correlate with DPD activity. Patients who responded to preoperative chemotherapy had lower DPD mRNA levels. Based on these results, we anticipate that measurement of DPD expression in clinical specimens may be clinically useful in managing advanced gastric cancer.

Adenocarcinoma↗

Orthotopic ileal neobladder in male patients: functional outcomes of 66 cases.

BACKGROUND: Orthotopic urinary diversion has become the preferred form of bladder reconstruction after cystectomy. We report on our experience with 66 male patients undergoing this procedure from November 1990 to February 1998. METHODS: A neobladder was constructed using an ileal segment with a Hautmann type bladder. Complications were assessed and subdivided into early and late types. Voiding function was evaluated in terms of voiding pattern and continence. Median follow up was 19.5 (range 3.5-87.7) months. RESULTS: There was one (1.5%) perioperative death. The most frequent pouch-related and unrelated early complications were persistent urine leak (7.6%) and prolonged ileus (16.7%), respectively, the majority of cases of which were managed conservatively. Analysis of late complications revealed 6.2% ureteroileal stenosis and 1.5% urethrointestinal stenosis rates, but no case of bladder stone formation. Of the 61 patients in whom voiding function was evaluable, 95.1% achieved excellent daytime continence, while only 67.2% had night-time continence. With regard to posture at voiding, 23 (37.7%) voided in a sitting position. Three of the patients (4.9%) were unable to void and required regular intermittent catheterization. CONCLUSIONS: An orthotopic neobladder can be constructed with acceptable morbidity and excellent functional results. We believe that orthotopic urinary diversion offers an attractive alternative to a bladder substitute when cystectomy is required.

Adult↗

Recurrence of sigmoid colon carcinoma in the residual urethra after cystectomy.

INTRODUCTION: We report a case of recurrence of sigmoid colon cancer in the residual urethra after cysto-prostato-sigmoidectomy. METHODS/RESULTS: The patient successfully underwent urethrectomy and is currently tumor-free. To our knowledge, this is the first case of recurrence of a non-urothelial malignant tumor in the residual urethra.

Adenocarcinoma↗

[Prevalence of upper urinary tract stones in Tajima, north Hyogo, Japan].

Toyooka Hospital is a central hospital in Tajima, a rural area in the northern part of Hyogo Prefecture. Because we possess the sole lithotripter in this area, almost all urolithiasis patients requiring treatment have been referred to our department. Based on the number of urolithiasis patients treated in our institution, we estimated the annual prevalence and incidence of upper urinary tract stones in the Tajima area. The mean annual prevalence of urolithiasis and incidence during the 1991-1993 period were 141 and 93 per 100,000, respectively. The male to female ratio was 2.0 to 1 in prevalence and 2.2 to 1.0 in incidence. Prevalence was highest in the sixties (245) and fifties (235), followed by the forties (205), seventies (162) and thirties (160). The incidence was highest in the fifties (169), followed by the forties (147), sixties (145) and thirties (118). In consideration of sex, the incidence was highest in males in the fifties and the forties. Of the patients with upper urinary calculi, 23.1% were treated by extracorporeal shock wave lithotripsy, while in 23.8% stones passed spontaneously and 50.9% were followed up without treatment. On stone analysis, calcium oxalate and/or calcium phosphate was present in 75.6%, uric acid in 16.4%, struvite and/or carbonate apatite in 5.6% and cystine in 1.4%. In summary, the prevalence and incidence of upper urinary tract calculi in the Tajima area were considerably higher than those in the nationwide survey on urolithiasis in Japan conducted in 1985.

Adult↗

First-pass metabolism of peptide drugs in rat perfused liver.

To elucidate the extent and mechanisms of the first-pass metabolism of peptide drugs in the liver after oral administration, a liver perfusion study was performed in rats using metkephamid, a stable analogue of methionine enkephalin, and thyrotropin-releasing hormone (TRH), as model peptides. The fraction of intact metkephamid recovered after single-pass constant perfusion through rat liver reached steady-state very quickly, and it was concluded that metkephamid was hydrolysed enzymatically at the surface of hepatocytes or endothelial cells of microvessels, or both, rather than being taken up by hepatocytes. The fraction of metkephamid recovered intact was approximately 40% under protein-free conditions but increased to 70-75% on addition of bovine serum albumin (BSA) to the perfusate. The fraction of metkephamid bound to BSA was approximately 50% under these conditions, implying that only the free fraction of metkephamid in the plasma was metabolized in the liver. Calculations based on the tube model showed that approximately 30-35% of metkephamid absorbed from the intestine undergoes first-pass metabolism before entering the systemic circulation in-vivo. In contrast, the fraction of TRH metabolized in the liver was less than 10%, indicating a remarkably low contribution of first-pass metabolism to the bioavailability of TRH. These results show that hepatic first-pass metabolism of metkephamid contributes to its low systemic bioavailability. After intestinal absorption free metkephamid is rapidly hydrolysed on the surface of hepatocytes or endothelial cells, rather than being taken up by hepatocytes. This information has important implications in the oral delivery of many kinds of peptide.

Administration, Oral↗

A new interpretation of salicylic acid transport across the lipid bilayer: implications of pH-dependent but not carrier-mediated absorption from the gastrointestinal tract.

Transport of several monocarboxylic acids across the lipid bilayer was examined in liposomes consisting of egg yolk phosphatidylcholine and cholesterol. In the presence of inward proton gradient, salicylic acid (SA) was taken up rapidly by liposomes showing overshoot, saturation and competitive inhibition phenomena. These carrier-mediated like profiles of SA uptake can be explained by assuming a very high permeability through the liposomal membrane of protonated SA. Protonated SA in the extraliposomal solution (pH 5.8) was taken up by liposomes rapidly, followed by a redissociation to anion according to the intraliposomal pH (pH 7.5). The concentration gradient of protonated SA across the liposomal membrane is maintained until the intraliposomal pH decreased to the extraliposomal level, which facilitates the uptake of SA into liposomes. The permeability of the lipid bilayer to several compounds was estimated from the inhibitory effects of those compounds on SA uptake by liposomes. Good linear relationships were observed between their inhibitory effects on the liposomal uptake of SA and the permeability of the intestinal membrane to them determined both in vivo and in vitro. These results clearly indicate that the carrier-independent transport mechanism of monocarboxylic acids observed in liposomes significantly contributes to their absorption from the intestinal tract under physiological conditions.

Animals↗

[A case of transitional cell carcinoma and milk of calcium in a pyelocalyceal diverticulum].

A 66-year-old man presented with right flank pain and macroscopic hematuria. Abdominal radiographs and computed tomography revealed a right pyelocalyceal diverticulum with milk of calcium and a soft tissue mass inside it. Other examinations, including positive urine cytology and negative random bladder biopsies, suggested a malignant tumor of the pyelocalyceal diverticulum. The patient underwent right nephroureterectomy. Histopathological examination revealed grade 3 transitional cell carcinoma. This is the first case of transitional cell carcinoma and milk of calcium coexisting in the same pyelocalyceal diverticulum.

Aged↗

Analysis of drug permeation across Caco-2 monolayer: implication for predicting in vivo drug absorption.

PURPOSE: The aim of the present work is to characterize in vitro drug permeation processes across Caco-2 monolayer and to identify the advantages of this cultured cell system in predicting in vivo drug absorption after oral administration. METHODS: The passive permeability of various drugs through Caco-2 monolayer was measured using Ussing-type chambers and compared with that of the isolated rat jejunum and colon. The in vivo drug permeability to the intestinal membrane was estimated by means of an intestinal perfusion study using the rat jejunum. RESULTS: In Caco-2 monolayer, drug permeability increased with increasing drug lipophilicity and showed a good linear relationship with the in vivo permeability. In contrast, in the isolated jejunum and colon, the permeability of high lipophilic drugs was almost constant and, propranolol, a drug with the highest lipophilicity, hardly passed through the jejunal membrane in vitro. As a result, there was no significant relationship between in vitro and in vivo drug permeability in rat jejunum. However, the amount of drugs accumulated in the jejunal mucosa increased with increasing drug lipophilicity even under the in vitro condition. CONCLUSIONS: The permeation and the accumulation studies suggested that the rate-limiting process of in vitro permeation of lipophilic drugs through the intestinal membrane differs from that of in vivo drug absorption. On the other hand, drug permeation through Caco-2 monolayer, which consists of an epithelial cell layer and a supporting filter, is essentially the same process as that of in vivo drug absorption. We concluded that the simple monolayer structure of a cultured cell system provides a distinct advantage in predicting in vivo drug absorption.

Animals↗

Intracorporeal lithotripsy with the Swiss Lithoclast.

BACKGROUND: In addition to currently available modalities of intracorporeal lithotripsy (ultrasonic, electrohydraulic, and laser), a new ballistic lithotriptor known as the Swiss Lithoclast has recently gained attention. This study reports our experience with the Swiss Lithoclast in the endoscopic management of urinary calculi. METHODS: A total of 51 patients with urinary calculi were treated with the Swiss Lithoclast; one patient with a renal calculus, 28 with ureteral calculi, and 22 with lower urinary tract (bladder, urethra and Kock pouch) calculi. RESULTS: The Lithoclast successfully fragmented 94% of the calculi, independent of stone composition. Complete failure of fragmentation was not encountered. In six of the 10 upper ureteral calculi, stone fragments were pushed up into the calyces. Adjunctive extracorporeal shock wave lithotripsy for residual fragments was performed in six cases. The stone-free rate at one and three months was 84% and 88%, respectively. There were no intraoperative or long-term complications directly related to the use of this device. CONCLUSION: The Swiss Lithoclast is a safe and effective means of intracorporeal lithotripsy. Although suitable for mid and lower ureteral stones, the device has a risk of stone push-up in patients with upper ureteral stones.

Adult↗

Quantitative evaluation of the gastrointestinal absorption of protein into the blood and lymph circulation.

In order to investigate the fate of orally administered proteins, the absorption of ovalbumin (OVA) from the gastrointestinal tract into both the blood and lymph circulation was quantitatively evaluated. After oral administration, a significant amount of intact OVA was detected in both the plasma and the lymph fluid by means of a two-site enzyme immunoassay. The extent of absorption into the plasma, calculated from the area under the plasma concentration versus time curve of OVA after oral and intravenous administration, was only 0.007-0.008% of the dose. This value is extremely low compared to that after nasal administration, showing the stronger barrier function of the gastrointestinal tract against the invasion of macromolecular proteins into the body. The extent of absorption into the lymph was dose-dependent (0.0007-0.002% of dose), and a higher dose leads to a higher fraction of OVA absorbed into the lymph. Moreover, it was demonstrated that not only the small intestine but also the stomach can absorb OVA. OVA absorbed from the stomach was transferred almost exclusively to the blood circulation, which suggests different mechanisms and/or routes of absorption between the stomach and the small intestine. In order to improve the low oral absorption, OVA was incorporated in liposomes and administered orally. Although the effect of liposomes was not significant, it increased OVA absorption into both the plasma and lymph by about 2 to 3-fold. It was considered that the liposomes suppressed the enzymatic degradation of OVA and released it slowly in the gastrointestinal tract.

Administration, Intranasal↗

Characterization of drug transport through tight-junctional pathway in Caco-2 monolayer: comparison with isolated rat jejunum and colon.

Drug transport through the tight-junctional pathway in Caco-2 monolayer was studied by examining the relationship between its permeability to hydrophilic drugs and membrane conductance. Compared with the rat isolated jejunum or colon, Caco-2 monolayer displayed high electrical resistance and low conductance, as well as low permeability to sulfanilic acid and FITC-dextran (M.W. 4000). However, there was a linear relationship between the drug permeability and partial Cl- ion conductance for Caco-2 monolayer, rat jejunum and colon. Hence, the permeability to those drugs per unit of Cl- conductance is similar in the three membranes, suggesting that the size (radius) of the tight-junctional pathway in the three membranes is similar. In addition, when the electrical resistance of Caco-2 monolayer was reduced to the same level as that of the jejunum or colon by pretreatment with disodium ethylenediaminetetraacetate, its permeability to FITC-dextran became significantly higher than that of other membranes. Accordingly, the high resistance and the low permeability of Caco-2 monolayer compared with rat intestinal membrane may be due to structural differences between the membranes, rather than a difference in the tightness of the junction.

Animals↗

Epidural anesthesia modifies cardiovascular responses to severe hypoxia in dogs.

Hypoxia is a critical and sometimes fatal complication of anesthesia. Since there is little information on the cardiovascular response to hypoxia during epidural anesthesia, we assessed the effects of epidural anesthesia on the cardiovascular response to hypoxia and on survival in dogs. We randomly assigned 36 mongrel dogs to one of three groups according to the anesthetic technique used: the thoracic group (n = 12) received thoracic epidural anesthesia plus general anesthesia, the thoracolumbar group (n = 12) received thoracolumbar epidural anesthesia plus general anesthesia, and the control group (n = 12) received general anesthesia alone. We monitored hemodynamics and plasma catecholamine concentrations and assessed survival in these groups during normocapnic hypoxia (FiO2, 0.09 for 120 min). During hypoxic challenge, PaCO2 and PaO2 values were similar in all groups. In both groups that received epidural anesthesia, heart rate, systolic and diastolic arterial pressures, and plasma epinephrine and norepinephrine concentrations were lower and arterial pH was greater than in the control group. There was no significant difference in survival among groups. Epidural anesthesia modified both the physiologic cardiovascular and catecholamine responses to hypoxia. Epidural anesthesia of the thoracic region did not appear to accelerate cardiac arrest, but it attenuated the development of metabolic acidosis during hypoxia.

Anesthesia, Epidural↗

Direct drug transport from the rat nasal cavity to the cerebrospinal fluid: the relation to the molecular weight of drugs.

To clarify the relationship between the direct transport from the rat nasal cavity to the cerebrospinal fluid (CSF) and the molecular weight of the drug, the transport of fluorescein isothiocyanate-labelled dextran (FD) with various molecular weights was investigated. FDs (average molecular weights 4,400 (FD4); 9,400 (FD10); 18,900 (FD20); 40,500 Da (FD40)) were administered nasally or intravenously to rats, and the concentrations in the plasma and the CSF were measured and compared. None of the FDs were detected in the CSF after intravenous administration. However, FD4, FD10 and FD20 were observed to appear in the CSF after nasal administration, whereas the concentration in the plasma was much lower than that after intravenous administration. FD40 was not detected even after nasal administration. In addition, the concentration of these FDs in the CSF decreased with the increase in the molecular weight of FDs. These findings show that drugs with a molecular weight up to at least 20,000 Da can be directly transported from the nasal cavity to the CSF and that the transport of FDs to the CSF is dependent on their molecular weights.

Administration, Intranasal↗

Gastrointestinal absorption of peptide drug: quantitative evaluation of the degradation and the permeation of metkephamid in rat small intestine.

The intestinal absorption of metkephamid (MKA), an analog of natural [Met]enkephalin, was investigated by means of vascular perfusion of the rat small intestine. Most of the MKA administered to the jejunal loop was degraded in the lumen by enzymatic hydrolysis, whereas only 0.3 to 1.2% of it was absorbed into the vascular flow. This means that enzymatic degradation is a major barrier against the intestinal absorption of MKA. The absorption of MKA was divided into two steps, degradation and permeation, and is expressed as clearance from the intestine. The degradation clearance (CLd) of MKA was 60- to 200-fold higher than the permeation clearance (CLp), indicating the rapid hydrolysis of MKA before absorption. The absorbed fraction of MKA increased with increasing luminal MKA concentration, mainly due to an increase in CLp rather than a decrease in CLd. MKA was degraded not only before absorption but also during permeation across the intestinal epithelium. Three kinds of enzyme inhibitors were co-administered with MKA into the intestinal loop. Puromycin, an aminopeptidase M inhibitor, markedly enhanced MKA absorption by both decreasing CLd and increasing CLp, indicating the predominant role of this enzyme in MKA degradation. Bestatin, another aminopeptidase M inhibitor, also effectively suppressed the degradation of MKA before absorption, whereas it only slightly increased CLp. It was further found that bestatin was less effective in inhibiting MKA hydrolysis during permeation. Thiorphan, an enkephalinase inhibitor, had no effect on MKA absorption.

Amino Acid Sequence↗

Kinetic analysis of the drug permeation process across the intestinal epithelium.

The rat intestinal lumen and the blood vessel were simultaneously perfused to study drug permeation across the intestinal epithelium. On the basis of drug disappearance from the intestinal lumen and its appearance into the vascular outflow, the mean time required for permeation across the intestinal membrane (MPT) and the permeation clearance (CLp) were calculated. MPT values of water, antipyrine, propranolol, imipramine and mannitol, varied from 0.45 min to 9.91 min depending on their physicochemical property. From both MPT and CLp, five drugs were classified as being (i) highly and rapidly absorbed (water, antipyrine), (ii) highly but slowly absorbed (propranolol, imipramine) and (iii) low and slowly absorbed (mannitol). Permeation profiles of these drugs were analyzed based on the diffusion model which defined the parameter for each permeation process, i.e. partitioning to and diffusion through the epithelium and clearance into the blood flow. Propranolol and imipramine partitioned into the membrane at a higher level than the other drugs. However, the clearance of both drugs from the epithelium was extremely slow, suggesting that this process is the rate-limiting step in their permeation. On the other hand, the rate-limiting step in the permeation of water and antipyrine was found to be the diffusion process in the epithelial layer.

Animals↗