Aliskiren attenuates proteinuria in mice with lupus nephritis by a blood pressure-independent mechanism.

This study revealed that low-dose aliskiren treatment could attenuate proteinuria by interrupting the renin-angiotensin system in mice with lupus nephritis, and the beneficial effect was beyond blood pressure control. An in and ex vivo fluorescence imaging (using a non-invasion in vivo imaging system) showed intense labeling of renin in the kidneys of female MRL/lpr mice. In the study, Alzet mini-osmotic pumps were implanted into 6-week-old female MRL/lpr mice. Pumps were filled with either phosphate-buffered saline or a solution of aliskiren dissolved in phosphate-buffered saline (20 mg/kg/day) and replaced at 28-day intervals. Mice were sacrificed at four and eight weeks. To label cells for DNA synthesis, bromodeoxyuridine (BrdU) (50 mg/kg) was injected intraperitoneally an hour prior to sacrifice. The level of renin inhibition was adequate, as aliskiren-treated mice demonstrated higher renal renin mRNA expression than controls (p < 0.05). Although there were no significant differences in the systolic blood pressure (control versus aliskiren-treated: 127.20 ± 4.44 mmHg versus 103.80 ± 7.40 mmHg, p > 0.05) and heart rate (control versus aliskiren-treated: 680.50 ± 11.71 versus 647.80 ± 13.90, p > 0.05) of both groups after eight weeks, there was significant reduction of inflammatory cytokines (transforming growth factor-beta1, regulated on activation normal T cell expressed, monocyte chemoattractant protein-1 and osteopontin, p < 0.05), reduction of innate immunity (toll-like receptor 7, p < 0.05), as well as a reduction of glomerular proliferation and inflammation (BrdU-, CD45-, CD3- and F4/80-positive glomerular cells, p < 0.01) after aliskiren infusion, which might translate into an improvement in proteinuria (control versus aliskiren-treated: 493.7 versus 843.7 mg/g, p < 0.01) or weight gain (control versus aliskiren-treated: 5.65 ± 1.61 versus 8.67 ± 0.97%, p < 0.05).

Sire pedigree error estimation and sire verification of the Taiwan dairy cattle population by using SNP markers.

Information regarding the correct pedigree of and relationship between animals is useful for managing dairy breeding, reducing inbreeding, estimating breeding value, and establishing correct breeding programs. Additionally, the successful implementation of progeny testing is crucial for improving the genetics of dairy cattle, which depends on the availability of correct pedigree information. Incorrect pedigree information leads to bias in bull evaluation. In this study, Neogen GeneSeek Genomic Profiler (GGP) 50K SNP chips were used to identify and verify the sire of Taiwanese Holstein dairy cattle and analyze the reasons that lead to incorrect sire records. Samples were collected from 2,059 cows of 36 dairy farms, and the pedigree information was provided by breeders. The results of sire verification can be divided into three categories: submitted unconfirmed sire, submitted confirmed sire, and incorrectly submitted verified sire. Data on the sires of 1,323 (64.25%) and 572 (27.78%) dairy cows were verified and discovered, respectively. Sires of 1,895 (92.03%) dairy cattle were identified, which showed that the paternal pedigree of dairy cattle could be discovered and verified through genetic testing. An error-like analysis revealed that the data of 37 sires were incorrectly recorded because the bull's NAAB code number was incorrectly entered into the insemination records: for 19 sires, the wrong bull was recorded because the frozen semen of a bull placed in the wrong storage tank was used, 6 had no sire records, and for 12 sires, the NAAB code of the correct bull was recorded but with a wrong stud code, marketing code, or unique number for the stud or breed. To reduce recorded sire error rates by at least 27.78%, automated identification of the mated bull must be adopted to reduce human error and improve dairy breeding management on dairy farms.

Atrial tachycardia induces remodelling of muscarinic receptors and their coupled potassium currents in canine left atrial and pulmonary vein cardiomyocytes.

BACKGROUND AND PURPOSE: Both parasympathetic tone and atrial tachycardia (AT) remodelling of ion channels play important roles in atrial fibrillation (AF) pathophysiology. Different muscarinic cholinergic receptor (mAChR) subtypes (M2, M3, M4) in atrial cardiomyocytes are coupled to distinct K+-currents (called IKM2, IKM3, IKM4, respectively). Pulmonary veins (PVs) are important in AF and differential cholinergic current responses are a potential underlying mechanism. This study investigated AT-induced remodelling of mAChR subtypes and K+-currents in left-atrial (LA) and PV cardiomyocytes. EXPERIMENTAL APPROACH: Receptor expression was assayed by western blot. IKM2, IKM3 and IKM4 were recorded with whole-cell patch-clamp in LA and PV cardiomyocytes of nonpaced control dogs and dogs after 7 days of AT-pacing (400 bpm). KEY RESULTS: Current densities of IKM2, IKM3 and IKM4 were significantly reduced by AT-pacing in LA and PV cardiomyocytes. PV cardiomyocyte current-voltage relations were similar to LA for all three cholinergic currents, both in control and AT remodelling. Membrane-protein expression levels corresponding to M2, M3 and M4 subtypes were decreased significantly (by about 50%) after AT pacing. Agonist concentration-response relations for all three currents were unaffected by AT pacing. CONCLUSIONS AND IMPLICATIONS: AT downregulated all three mAChR-coupled K+-current subtypes, along with corresponding mAChR protein expression. These changes in cholinergic receptor-coupled function may play a role in AF pathophysiology. Cholinergic receptor-coupled K+-currents in PV cardiomyocytes were similar to those in LA under control and AT-pacing conditions, suggesting that differential cholinergic current properties do not explain the role of PVs in AF.

Tyr115, gln165 and trp209 contribute to the 1, 2-epoxy-3-(p-nitrophenoxy)propane-conjugating activity of glutathione S-transferase cGSTM1-1.

We investigated the epoxidase activity of a class mu glutathione S-transferase (cGSTM1-1), using 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) as substrate. Trp209 on the C-terminal tail, Arg107 on the alpha4 helix, Asp161 and Gln165 on the alpha6 helix of cGSTM1-1 were selected for mutagenesis and kinetic studies. A hydrophobic side-chain at residue 209 is needed for the epoxidase activity of cGSTM1-1. Replacing Trp209 with histidine, isoleucine or proline resulted in a fivefold to 28-fold decrease in the k(cat)(app) of the enzyme, while a modest 25 % decrease in the k(cat)(app) was observed for the W209F mutant. The rGSTM1-1 enzyme has serine at the correponding position. The k(cat)(app) of the S209W mutant is 2. 5-fold higher than that of the wild-type rGSTM1-1. A charged residue is needed at position 107 of cGSTM1-1. The K(m)(app)(GSH) of the R107L mutant is 38-fold lower than that of the wild-type enzyme. On the contrary, the R107E mutant has a K(m)(app)(GSH) and a k(cat)(app) that are 11-fold and 35 % lower than those of the wild-type cGSTM1-1. The substitutions of Gln165 with Glu or Leu have minimal effect on the affinity of the mutants towards GSH or EPNP. However, a discernible reduction in k(cat)(app) was observed. Asp161 is involved in maintaining the structural integrity of the enzyme. The K(m)(app)(GSH) of the D161L mutant is 616-fold higher than that of the wild-type enzyme. In the hydrogen/deuterium exchange experiments, this mutant has the highest level of deuteration among all the proteins tested. We also elucidated the structure of cGSTM1-1 co-crystallized with the glutathionyl-conjugated 1, 2-epoxy-3-(p-nitrophenoxy)propane (EPNP) at 2.8 A resolution. The product found in the active site was 1-hydroxy-2-(S-glutathionyl)-3-(p-nitrophenoxy)propane, instead of the conventional 2-hydroxy isomer. The EPNP moiety orients towards Arg107 and Gln165 in dimer AB, and protrudes into a hydrophobic region formed by the loop connecting beta1 and alpha1 and part of the C-terminal tail in dimer CD. The phenoxyl ring forms strong ring stacking with the Trp209 side-chain in dimer CD. We hypothesize that these two conformations represent the EPNP moiety close to the initial and final stages of the reaction mechanism, respectively.

Reappraisal of percutaneous transhepatic cholangioscopic lithotomy for primary hepatolithiasis.

BACKGROUND: A review of the literature pertaining to percutaneous transhepatic cholangioscopic lithotomy (PTCSL) showed that more than 50% of reported patients had undergone earlier biliary surgery. METHODS: A retrospective study investigated 74 patients undergoing initial PTCSL for hepatolithiasis who had undergone no prior biliary surgery or manipulation. The patients were followed for 1 to 23 years after PTCSL for effective evaluation of the procedure outcome. RESULTS: Complete clearance of hepatolithiasis was achieved for 61 (82%) patients. The incomplete clearance rate was higher for patients with intrahepatic duct stricture (11/37 [30%] vs 2/37 [5%]; p < 0.05), although it showed no relation to the actual lobar distribution of hepatolithiasis (left: 7/41 [17%] vs right: 2/11 [18%] vs bilateral: 4/22 [18%]; p < 0.05). The recurrence rate for hepatolithiasis also was higher for patients with intrahepatic duct stricture (18/26 [69%] vs 13/35 [37%]; p < 0.05), but the recurrence rate showed no relation to the lobar distribution of hepatolithiasis (left: 18/34 [53%] vs right: 4/9 [44%] vs bilateral: 9/18 [50%] p > 0.05) or the presence of gallbladder stones (5/12 [42%] vs 26/49 [53%]; p > 0.05). Patients showing the coexistence of retained or recurrent hepatolithiasis demonstrated a higher incidence of recurrent cholangitis (57% [13/23] vs 14% [7/51]; p < 0.01) or cholangiocarcinoma (17% [4/23]) vs 0% [0/51]; p < 0.01). CONCLUSIONS: The findings show that PTCSL is effective for treating primary hepatolithiasis, and that complete stone clearance is mandatory to diminish the sequelae of hepatolithiasis. Intrahepatic duct stricture was the main factor contributing to incomplete clearance and stone recurrence.

Emergency management and infection control in a radiology department during an outbreak of severe acute respiratory syndrome.

The World Health Organization classified Taiwan as a serious epidemic-stricken area when the extent of severe acute respiratory syndrome (SARS) in Taiwan became clear. As of 11 July 2003, 671 probable SARS cases had been identified in Taiwan and 7 healthcare workers had died from the disease. Radiographers were easily infected by SARS because they had close contact with suspected or probable cases while conducting chest X-ray examinations. Three radiographers had been infected by the end of May 2003. Because of the impact of SARS on the Radiology Department, the department established a SARS emergency infection control team and re-designed the department's infection-control and emergency-management procedures based on the concept of risk-grade protection. This effort included installing a radiographic room at the fever-screening station, re-allocating human resources in the Radiology Department, training the department staff in infection control, and drafting new operational procedures for radiographers conducting X-ray examinations on SARS patients. The goal of this program was to reduce the infection rate and distribute materials efficiently in the department. This article introduces the emergency-management procedure of the Radiology Department during the SARS outbreak and the infection-protection experience of the department staff.

Identification of cyprinol and cyprinol sulfate from grass carp bile and their toxic effects in rats.

To elucidate the responsible toxic components of grass carp bile, the bile salt 5 alpha-cyprinol sulfate and its desalted form 5 alpha-cyprinol from grass carp bile were purified and identified by analyses of infrared spectrum, (1)H-, (13)C-nuclear magnetic resonance spectra and mass spectrum. The toxicity of grass carp bile powder, butanol extract of grass carp bile powder, 5 alpha-cyprinol and 5 alpha-cyprinol sulfate in rats were further determined. The kidney and liver functions were significantly affected by grass carp bile powder, butanol extract and 5 alpha-cyprinol sulfate. However, 5 alpha-cyprinol also significantly affected the kidney function, but the toxic effect was less.

Percutaneous choledochoscopic biliary tract stone removal: experience in 645 consecutive patients.

Our experience in non-operative retrieval of biliary tract stones through PTCS (percutaneous transhepatic cholangioscopy, n = 103) and POC (post-operative choledochoscopy, n = 542) plus the use of Dormia basket and EHL (electrohydraulic lithotripsy) is presented. The results of transhepatic and T-tube routes are compared, with emphasis on the technical difficulties encountered. The success rates were 96% and 97% in POC and PTCS, respectively. No mortality was related to these procedures. Intrahepatic duct angulation and stricture were the factors most often responsible for failure. Postoperative choledochoscopic stone removal is safe and the method of choice for retained biliary tract calculi, while PTCS is highly indicated for those high-risk patients with or without previous biliary surgery. POC and PTCS have, therefore, their own indications and differ in their clinical applications.

Bilateral hepatic duct decompression via a single percutaneous tract using a 'mother-baby' drainage catheter.

Decompression of the right and left hepatic ducts using a 'mother-baby' self-made drainage system via a single percutaneous tract was performed successfully in 15 of 21 patients with benign (n = 4) and malignant (= 17) hilar obstruction. The 'mother-baby' drainage system was composed of an 18 F catheter placed through the right hepatic duct into the distal common bile duct which was designated as the 'mother' catheter, while a second 10 F baby catheter was placed through the first catheter into the left hepatic ducts. This was achieved by a three-stage procedure: (1) percutaneous transhepatic biliary drainage; (2) balloon dilatation of the tract; and (3) intubation of the contralateral hepatic duct and placement of the 'mother-baby' drainage catheters. The mean interval of stent clogging was 5 months, with a range of 2-9 months. In 12 malignant cases, average survival time was 9.8 months. The technique avoided a second percutaneous hepatic puncture in centrally obstructing lesions and afforded bilateral biliary decompression.

Role of upright chest radiography and ultrasonography in demonstrating free air of perforated peptic ulcers.

BACKGROUND/AIMS: The purpose of this study was to determine the value of upright chest radiography and ultrasonography in demonstrating free air of perforated peptic ulcers. METHOLOGY: Eighty-four patients with perforated peptic ulcers receiving both upright chest radiography and ultrasonography before laparotomy. The sensitivity of each modality in demonstrating free air was correlated. RESULTS: Among the 84 patients receiving both examinations, free air was demonstrated in only 39 (46%) upright chest radiographs and 46 (55%) ultrasonographs, the direct sign could be demonstrated in 57 (68%) patients by combined radiography and ultrasonography. Besides, the indirect sign of ascites could be demonstrated in 26 (31%) ultrasonographs. CONCLUSIONS: Ultrasonography is more sensitive than upright chest radiography to demonstrate free air of perforated peptic ulcers, and it should be considered in those patients of suspected perforated peptic ulcers with negative upright chest radiography. Combined methods of upright chest radiography and ultrasonography can increase the overall sensitivity in demonstrating free air.

The features of perforated peptic ulcers in conventional computed tomography.

BACKGROUND/AIMS: CT is not usually of priority to evaluate the pathology of the gastrointestinal tract, especially perforated peptic ulcer. However CT might be employed when the presentation is atypical. The study was to summarize the imaging features of perforated peptic ulcer in conventional CT and assess its ability of detecting perforated peptic ulcer. METHODOLOGY: The CTs of 14 consecutive patients with perforated peptic ulcer confirmed by operation were retrospectively reviewed. The CTs were obtained after intravenous contrast medium, but oral contrast medium was administered only in 5 patients. The CT findings were correlated with surgical findings. RESULTS: Among these 14 patients, all the 14 patients (100%) had extraluminal air accumulation, 10 patients (71%) had abnormal fluid accumulation, and 5 (36%) patients had inflammatory changes in surrounding soft tissues. In addition, conventional CT could only demonstrate the site of perforation in 5 patients (36%) of them. CONCLUSIONS: Conventional CT was valuable in the diagnosis of perforated peptic ulcer, and pneumoperitoneum was the most common feature. However the ability of conventional CT in localizing the site of perforation was poor.

The accuracy of endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, computed tomography, and transabdominal ultrasound in the detection and staging of primary ampullary tumors.

BACKGROUND/AIMS: To compare the accuracy between EUS (endoscopic ultrasound), ERCP (endoscopic retrograde cholangiopancreatography), CT (computed tomography), and transabdominal US (ultrasound) in the detection and staging of primary ampullary tumors. We will also try to discuss the influence of endobiliary stent on EUS in staging ampullary tumors. METHODOLOGY: Twenty-one patients with ampullary tumors were evaluated by EUS, ERCP, CT, and US before operation. The accuracy was assessed with TNM staging and compared with the surgical-pathological findings. RESULTS: EUS was superior to CT and US in detecting ampullary tumors, but EUS and ERCP are of similar sensitivity (EUS 95%, ERCP 95%, CT 19%, US 5%). EUS was superior to CT and US in T staging (EUS 75%, CT 5%, US 0%) and detecting lymph node metastasis (EUS 50%, CT 33%, US 0%) of ampullary tumors. The accuracy of EUS in T and N staging of ampullary tumors tended to be decreased in the presence of endobiliary stent (stenting: T 71%, N 75%; nonstenting T 83%, N 100%), but there was no statistical significance. CONCLUSIONS: EUS was superior to CT and US in assessing primary ampullary tumors, but it was not significantly superior to ERCP in detecting ampullary tumors. The presence of endobiliary stent may decrease the accuracy of EUS in staging ampullary tumors.

Self-expandable metallic stents in the management of malignant biliary obstruction.

To overcome problems with conventional plastic endoprostheses, a study was conducted to determine the clinical efficacy of self-expandable metallic stents in the palliative treatment of malignant biliary obstruction. From May 1994 to March 1995, 19 self-expandable metallic stents were implanted in 13 consecutive patients with malignant obstructive jaundice due to cholangiocarcinoma (four patients), ampullary carcinoma (six), pancreatic carcinoma (one), and hepatic hilar lymph node metastasis (two). All patients underwent percutaneous transhepatic biliary drainage followed by stent insertion, except for two patients where the T-tube tract was used as access and another with previous placement of a polyethylene internal-external drainage catheter for more than 6 months. When both lobes of the biliary system were to be drained, stents were placed either side by side through punctured, separate hepatic ducts or, using a T configuration, through a single transhepatic tract. Percutaneous transhepatic stent placement was technically successful in all patients. After a mean follow-up of 5.9 months (range, 1-10 mo), 10 of 13 patients were still alive while three had died of nonprocedure-related causes. In 10 patients, total serum bilirubin levels decreased significantly (from 136.8 +/- 157 mumol/L to 34.2 +/- 22.2 mumol/L), while it increased in three patients. Two patients had stent occlusions at 2 and 3 months after stent placement, which required intervention. The overall patency period ranged from 1 to 9 months (mean, 5.1 mo). Our results confirm that the use of metallic stents is effective in the palliative treatment of malignant jaundice.

Estimation of mean-glandular dose from monitoring breast entrance skin air kerma using a high sensitivity metal oxide semiconductor field effect transistor (MOSFET) dosimeter system in mammography.

Estimation of mean-glandular dose (MGD) has been investigated in recent years due to the potential risks of radiation-induced carcinogenesis associated with the mammographic examination for diagnostic radiology. In this study, a new technique for immediate readout of breast entrance skin air kerma (BESAK) using high sensitivity MOSFET dosimeter after mammographic projection was introduced and a formula for the prediction of tube output with exposure records was developed. A series of appropriate conversion factors was applied to the MGD determination from the BESAK. The study results showed that signal response of the high sensitivity MOSFET exhibited excellent linearity within mammographic dose ranges, and that the energy dependence was less than 3% for each anode/filter combination at the tube potentials 25-30 kV. Good agreement was observed between the BESAK and the tube exposure output measurement for breasts thicker than 30 mm. In addition, the air kerma estimated from our prediction formula provided sufficient accuracy for thinner breasts. The average MGD from 120 Asian females was 1.5 mGy, comparable to other studies. Our results suggest that the high sensitivity MOSFET dosimeter system is a good candidate for immediately readout of BESAK after mammographic procedures.

Development of an imaging-planning program for screen/film and computed radiography mammography for breasts with short chest wall to nipple distance.

OBJECTIVE: Imaging breasts with a short chest wall to nipple distance (CWND) using a traditional mammographic X-ray unit is a technical challenge for mammographers. The purpose of this study is the development of an imaging-planning program to assist in determination of imaging parameters of screen/film (SF) and computed radiography (CR) mammography for short CWND breasts. METHODS: A traditional mammographic X-ray unit (Mammomat 3000, Siemens, Munich, Germany) was employed. The imaging-planning program was developed by combining the compressed breast thickness correction, the equivalent polymethylmethacrylate thickness assessment for breasts and the tube loading (mAs) measurement. Both phantom exposures and a total of 597 exposures were used for examining the imaging-planning program. RESULTS: Results of the phantom study show that the tube loading rapidly decreased with the CWND when the automatic exposure control (AEC) detector was not fully covered by the phantom. For patient exposures with the AEC fully covered by breast tissue, the average fractional tube loadings, defined as the ratio of the predicted mAs using the imaging-planning program and mAs of the mammogram, were 1.10 and 1.07 for SF and CR mammograms, respectively. The predicted mAs values were comparable to the mAs values, as determined by the AEC. CONCLUSION: By applying the imaging-planning program in clinical practice, the experiential dependence of the mammographer for determination of the imaging parameters for short CWND breasts is minimised.