Longitudinal changes in 18 F-THK5351 positron emission tomography in corticobasal syndrome.

BACKGROUND AND PURPOSE: Corticobasal syndrome (CBS) is pathologically characterized by tau deposits in neuronal and glial cells and by reactive astrogliosis. In several neurodegenerative disorders, 18 F-THK5351 has been observed to bind to reactive astrocytes expressing monoamine oxidase B. In this study, the aim was to investigate the progression of disease-related pathology in the brains of patients with CBS using positron emission tomography with 18 F-THK5351. METHODS: Baseline and 1-year follow-up imaging were acquired using magnetic resonance imaging and positron emission tomography with 18 F-THK5351 in 10 subjects: five patients with CBS and five age-matched normal controls (NCs). RESULTS: The 1-year follow-up scan images revealed that 18 F-THK5351 retention had significantly increased in the superior parietal gyrus of the patients with CBS compared with the NCs. The median increases in 18 F-THK5351 accumulation in the patients with CBS were 6.53% in the superior parietal gyrus, 4.34% in the precentral gyrus and 4.33% in the postcentral gyrus. In contrast, there was no significant increase in the regional 18 F-THK5351 retention in the NCs. CONCLUSIONS: Longitudinal increases in 18 F-THK5351 binding can be detected over a short interval in the cortical sites of patients with CBS. A monoamine oxidase B binding radiotracer could be useful in monitoring the progression of astrogliosis in CBS.

Effects of early experience with low-quality roughage on feed intake, digestibility and metabolism in lambs.

The objective of this study was to compare the feed intake, digestibility and metabolism in lambs fed low-quality roughage with those of lambs fed normal roughage from an early stage of their life. The study consisted of two treatments [low-quality roughage group (LR) and control group (C)] over three time periods (P1, P2 and P3; 2 months each). Four lambs (4 months old) were allocated to each treatment. In P1 and P2, LR was fed sudangrass hay (CP: 5.1% DM; NDF: 70.4% DM), whereas C was fed timothy hay (CP: 8.4% DM; NDF: 60.3% DM). In P3, all lambs were fed sudangrass hay. Although the feed intake was significantly greater (p < 0.05) in C in P1, there were no differences between the groups in P2. The digestibility, serum glucose (GLU), urea nitrogen (SUN) and insulin-like growth factor 1 (IGF-1) did not differ between the groups in P1 and P2. The average nitrogen retention, triiodothyronine (T3) and thyroxine (T4) were significantly higher in C (p < 0.05) during P1 and P2. No interaction was observed between the treatment and periods. In P3, the feed intake was greater in C (p < 0.05), whereas digestibility and nitrogen retention tended to be greater in LR. The body weight did not differ between the treatments. T4 and T3 were numerically lower in LR, while the SUN was greater in LR (p < 0.05). These results suggest that the early experience with low-quality roughage may have improved feed digestibility and nitrogen metabolism in lambs after 4 months of rearing. Furthermore, the experienced lambs became more efficient at utilizing the low-quality roughage. The lower thyroid hormone concentrations observed in LR suggest an adaptive change occurred in experienced lambs that to a lower basal metabolic rate.

Impact of videogame play on the brain's microstructural properties: cross-sectional and longitudinal analyses.

Videogame play (VGP) has been associated with numerous preferred and non-preferred effects. However, the effects of VGP on the development of microstructural properties in children, particularly those associated with negative psychological consequences of VGP, have not been identified to date. The purpose of this study was to investigate this issue through cross-sectional and longitudinal prospective analyses. In the present study of humans, we used the diffusion tensor imaging mean diffusivity (MD) measurement to measure microstructural properties and examined cross-sectional correlations with the amount of VGP in 114 boys and 126 girls. We also assessed correlations between the amount of VGP and longitudinal changes in MD that developed after 3.0±0.3 (s.d.) years in 95 boys and 94 girls. After correcting for confounding factors, we found that the amount of VGP was associated with increased MD in the left middle, inferior and orbital frontal cortex; left pallidum; left putamen; left hippocampus; left caudate; right putamen; right insula; and thalamus in both cross-sectional and longitudinal analyses. Regardless of intelligence quotient type, higher MD in the areas of the left thalamus, left hippocampus, left putamen, left insula and left Heschl gyrus was associated with lower intelligence. We also confirmed an association between the amount of VGP and decreased verbal intelligence in both cross-sectional and longitudinal analyses. In conclusion, increased VGP is directly or indirectly associated with delayed development of the microstructure in extensive brain regions and verbal intelligence.

Brain structural changes as vulnerability factors and acquired signs of post-earthquake stress.

Many survivors of severe disasters, even those without posttraumatic stress disorder (PTSD), need psychological support. To understand the pathogenesis of PTSD symptoms and prevent the development of PTSD, the critical issue is to distinguish neurological abnormalities as vulnerability factors from acquired signs of PTSD symptoms in the early stage of adaptation to the trauma in the normal population. The neurological underpinnings of PTSD have been well characterized, but the causal relationships with the traumatic event are still unclear. We examined 42 non-PTSD subjects to find brain morphometric changes related to the severity of PTSD symptoms in a longitudinal magnetic resonance imaging study extending through the Great East Japan Earthquake. We found that regional grey matter volume (rGMV) in the right ventral anterior cingulate cortex (ACC) before the earthquake, and decreased rGMV in the left orbitofrontal cortex (OFC) through the earthquake were negatively associated with PTSD symptoms. Our results indicate that subjects with smaller GMV in the ACC before the earthquake, and subjects with decreased GMV in the OFC through the earthquake were likely to have PTSD symptoms. As the ACC is involved in processing of fear and anxiety, our results indicate that these processing are related to vulnerability for PTSD symptoms. In addition, decreased OFC volume was induced by failing to extinct conditioned fear soon after the traumatic event. These findings provide a better understanding of posttraumatic responses in early stage of adaptation to the trauma and may contribute to the development of effective methods to prevent PTSD.

A rapid HPLC with evaporative light scattering method for quantification of forskolin in multi-herbal weight-loss solid oral dosage forms.

A rapid reverse-phase HPLC method with evaporative light scattering detection (ELSD) was developed for the determination of forskolin in weight loss multi-herbals products. The analysis was performed by water-acetonitrile gradient elution at a temperature of 40 degrees C and a flow rate of 1.0 mL/min. The evaporator tube temperature of ELSD was set at 35 degrees C, and with the nebulizing gas flow-rate (pressure) of 3.0 bar. The method was validated for linearity, accuracy, precision and limits of detection (LOD) and quantification (LOQ). Good linear relationships were obtained with correlation coefficients exceeding 0.9995. The average recovery of forskolin ranged from 99.4% to 100.4% with RSDs below 3%. The percent relative standard deviations (%RSD) of intra- and inter-day precision varied by less than 2.1%. LOD and LOQ were 0.95 microg/ml and 3.21 microg/ml, respectively. The validated ELSD method permits a shorter determination time without compromising accuracy and demonstrates that it can be used for quantification of forskolin incorporated in multi-herbal solid oral dosage forms.

Psychiatric, somatic, and gastrointestinal disorders, and Helicobacter pylori infection in children with recurrent abdominal pain.

AIMS: To examine the utility of the Rome II criteria in children with recurrent abdominal pain (RAP) and compare them to those who met Apley's criteria and those who met neither criteria. METHODS: Prospective study in general paediatric clinics in Komagane, Japan. Children with abdominal pain were classified into those who met Rome II criteria, those who met Apley's criteria, and those who met neither. RESULTS: A total of 182 children with RAP participated; 45 children met Rome II criteria, 55 met Apley's criteria, and 82 met neither. Children who met Rome II criteria had a significantly higher prevalence of psychiatric and somatic disorders compared to the group met neither (36% v 6%, 22% v 10%, respectively). The overall prevalence of H pylori was 7%; prevalence increased with age from 3% at age < or = 10 to 10% for children >10 years. Children who met Rome II criteria had a significantly higher prevalence of H pylori infection than the reference group (18% v 4%). In a logistic regression model, all the study variables were included in the model specifying first the Rome II criteria group as the independent variable; psychiatric disorders, H pylori infection, and older age group were independent risk factors. CONCLUSIONS: More than half the children suffering from recurrent abdominal pain met neither Apley's nor Rome II criteria. Children who meet Rome II criteria should be evaluated for psychiatric disorders and should be tested for H pylori infection. Despite the overall trend for a fall in the prevalence of H pylori infection among children in Japan, there are subpopulations of sick children where the prevalence of the infection is relatively high.

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.

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.

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.

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.

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.

[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.

A case of hydronephrosis caused by arteriosclerotic compression of the renal pelvis.

We present the case of a 65-year-old woman with vascular compression of the renal pelvis, causing calyectasis. The diagnosis was a subtype of Fraley's syndrome. The cause of compression was concluded to be arteriosclerotic change of both the renal artery and the abdominal aorta.

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.

[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.

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.

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.

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.