Aldosterone: a mediator of retinal ganglion cell death and the potential role in the pathogenesis in normal-tension glaucoma.

Glaucoma is conventionally defined as a chronic optic neuropathy characterized by progressive loss of retinal ganglion cells (RGCs) and optic nerve fibers. Although glaucoma is often associated with elevated intraocular pressure (IOP), significant IOP reduction does not prevent progression of the disease in some glaucoma patients. Thus, exploring IOP-independent mechanisms of RGC loss is important. We describe chronic systemic administration of aldosterone and evaluate its effect on RGCs in rat. Aldosterone was administered via an osmotic minipump that was implanted subcutaneously into the mid-scapular region. Although systemic administration of aldosterone caused RGC loss associated with thinning of the retinal nerve fiber layer without elevated IOP, the other cell layers appeared to be unaffected. After chronic administration of aldosterone, RGC loss was observed at 2 weeks in the peripheral retina and at 4 weeks in the central retina. However, administration of mineralocorticoid receptor blocker prevented RGC loss. These results demonstrate aldosterone is a critical mediator of RGC loss that is independent of IOP. We believe this rat normal-tension glaucoma (NTG) animal model not only offers a powerful system for investigating the mechanism of neurodegeneration in NTG, but can also be used to develop therapies directed at IOP-independent mechanisms of RGC loss.

Phosphorus recovery from artificial wastewater by microbial fuel cell and its effect on power generation.

The effects of ammonium (NH4) and magnesium (Mg) on the precipitation of phosphorus in artificial wastewater by an air-cathode single-chamber microbial fuel cell were investigated. When both NH4 and Mg were added to the wastewater, phosphorus was precipitated as struvite. Almost no precipitation occurred with the addition of only NH4, while phosphorus was precipitated as cattiite with the addition of only Mg. However, the amount of precipitate was less than that observed in experiments in which NH4 was also added. As the amounts of NH4 and Mg were increased, more precipitate was observed. Precipitated phosphorus on the cathode was recovered by dissolution in Milli-Q water and MES buffers. It was discovered that the formation of a precipitate reduced the performance of the cathode. Dissolution treatment caused the performance of the cathodes to increase to their initial level.

Removal and recovery of phosphorus as struvite from swine wastewater using microbial fuel cell.

Air-cathode single chamber microbial fuel cells (MFCs) were operated with swine wastewater. The maximum power density, the maximum current density, the average value of COD-removal efficiency, and the coulombic efficiency were 1-2.3 W/m(2), 6.0-7.0 A/m(2), 76-91%, and 37-47%, respectively. During operation, 70-82% of the phosphorus was removed from the influent, and some precipitations were observed on the surface of the liquid side of the cathodes. The amount of phosphorus contained in these precipitates was estimated to be equivalent 4.6-27% of the influent. The main component of these precipitates was revealed by X-ray diffraction analysis to be struvite. Furthermore, our results indicate that phosphorus in suspended solid form was first dissolved, and then precipitated on the cathode. By scanning electron microscope observation, the morphology of the precipitates was irregularly shaped, including crystals with hexagonal cross-section surfaces, and was different from the familiar needle-like ones. These results indicate that simultaneous recovery of electrical power and phosphorus from wastewater by microbial fuel cell is possible.

[Thoracic aortic aneurysm associated with pseudocoarctation; report of a case].

A 20-year-old woman without any significant history of disease was referred for further investigation of an aortic arch aneurysm. The arterial blood pressure in the right arm was higher than in the left arm and in both legs. An multi-detector row computed tomography (MDCT) and an aortogram revealed narrowing of the middle aortic arch, kinking at the ligamentum arteriosum, subsequent multiple aneurysmal formation, and stenosis and narrowing of the descending aorta. The left subclavian artery branched from the 1st aneurysm. We resected the aneurysms and reconstructed the distal aortic arch and left subclavian artery using a woven polyester graft. This case was diagnosed as thoracic aortic aneurysm associated with pseudocoarctation, which is a quite rare congenital anomaly.

Carvedilol accelerate elevation of serum potassium in chronic heart failure patients administered spironolactone plus furosemide and either enalapril maleate or candesartan cilexetil.

OBJECTIVE: To retrospectively investigate the effect of carvedilol and spironolactone plus furosemide, administered concomitantly with an angiotensin II converting enzyme inhibitor (ACE-I) or an angiotensin II receptor blocker (ARB) to patients with chronic heart failure (CHF). METHODS: Patients with CHF, who visited Departments of Cardiovascular Internal Medicine at the National Hospital Organization Osaka Medical Center, were enrolled for this study. Serum potassium, blood urea nitrogen (BUN), serum creatinine (Scr) and serum sodium were measured in every patient at the time of start of treatment and after 3 and 12 months of treatment. Data from patients in groups A (20 mg/day carvedilol + 25 mg/day spironolactone + 40 mg/day furosemide + an ACE-I) and B (20 mg/day carvedilol + 25 mg/day spironolactone + 40 mg/day furosemide + ARB) were compared. RESULTS: When 20 mg/day carvedilol plus 25 mg/day spironolactone plus 5 mg/day enalapril maleate (enalapril, group A) or 8 mg/day candesartan cilexetil (candesartan, group B) plus 40 mg/day furosemide were used concomitantly, the mean serum potassium increased significantly in both groups of patients. Seven of 59 (11.9%) patients had hyperkalemia (>5.5 mEq/L) during 12 months of treatment whereas 8.5% of patients (five of 59) had hypokalemia (< or =3.5 mEq/L). CONCLUSION: When carvedilol is used concomitantly with spironolactone, furosemide and enalapril or candesartan, it is necessary to monitor serum potassium concentration, even if spironolactone is administered at a low dose of 25 mg/day.

Serum concentration of potassium in chronic heart failure patients administered spironolactone plus furosemide and either enalapril maleate, losartan potassium or candesartan cilexetil.

OBJECTIVE: To retrospectively investigate elevation of serum potassium when spironolactone (25 or 50 mg/day) and furosemide were administered concomitantly with an angiotensin II converting enzyme inhibitor (ACE-I) or angiotensin II receptor blocker (ARB) to patients with chronic heart failure for 12 months and occurrence of hyperkalemia and hypokalemia because of concomitant administration of spironolactone plus an ACE-I or ARB and furosemide. METHODS: Patients with chronic heart failure, who visited departments of cardiovascular internal medicine and cardiovascular surgery at the National Hospital Organization Osaka Medical Center, were enrolled for this study. Serum potassium, blood urea nitrogen (BUN), serum creatinine, uric acid, and serum sodium were determined in every patient at the time of start of treatment and at 3 and 12 months of treatment. Data from patients in Groups A (25 mg/day spironolactone + 40 mg/day furosemide + an ACE-I or ARB) and B (50 mg/day spironolactone + 40 mg/day furosemide + an ACE-I or ARB) were analysed for differences with respect to the ACE-I and ARB used. RESULTS: When 50 mg/day spironolactone plus 5 mg/day enalapril maleate (enalapril) or 50 mg/day losartan potassium (losartan) or 8 mg/day candesartan cilexetil (candesartan) plus 40 mg/day furosemide were concomitantly used, the mean value of serum potassium was significantly elevated only in the group treated with 50 mg/day spironolactone regardless of the concomitant drug. The number of patients with hyperkalemia (>5.5 mEq/L) at 12 months of treatment was 12 (8.8%), while the number of patients with hypokalemia (

Phage display cloning and characterization of monoclonal antibody genes and recombinant Fab fragment against the CD98 oncoprotein.

The Fab gene of anti-CD98 heavy chain (h.c.) monoclonal antibody (mAb) HBJ127 was cloned and expressed as a recombinant Fab (rFab) fragment by means of a phage display system. The variable heavy and light chain genes of HBJ127 were found to be derived from VOx-1 and IgVk8-30 germline, respectively. Extensive somatic mutation was found in the heavy chain complementarity determining region 2. rFab fragment was purified homogeneously from crude bacterial lysates by Ni-chelate chromatography in a yield of 71.4 mg from 100 ml of culture. rFab fragment was reactive with the cell surface of CD98-positive cells irrespective of tissues of origin, but not with CD98-negative cells. The recognition site of the rFab fragment was identical to that of mAb since the binding of rFab fragment to HeLaS(3) cells was completely inhibited by pretreatment with an excess of mAb. The relative affinity values of rFab fragment and mAb were found to be 0.11 x 10(8) and 0.35 x 10(8) M(-1), respectively. Three-fold lower affinity of rFab fragment may be due to the difference of valency of the antibody preparation. Cell growth inhibition in vitro by rFab fragment preincubated with anti-Fab suggests that the rFab fragment produced by cloned gene-bearing Escherichia coli was identical to the Fab part of HBJ127 mAb. These results show that a small fragment with antigen binding activity similar to that of the parent mAb can easily be prepared by using a phage display system. To our knowledge, this is a first report of the production of anti-CD98 h.c. rFab fragment.

[A case of extracardiac unruptured aneurysm of sinus of Valsalva with obstruction of the right coronary artery and aortic regurgitation].

A 67-year-old female was admitted to our hospital with heart failure. Echocardiography, chest CT and MRA revealed an unruptured aneurysm of sinus of Valsalva. Cardiac catheterization and angiography detected obstruction of the ostium of the right coronary artery and moderate aortic regurgitation. Operative findings showed an extracardiac unruptured aneurysm arising from the right sinus of Valsalva. The orifice of the aneurysm was closed with Gore-Tex patch, then aortic valve replacement combined with single CABG to RCA was simultaneously performed. The pathological findings strongly suggested its acquired origin.

Comparative left ventricular functional and neurohumoral effects of chronic treatment with carvedilol versus metoprolol in patients with dilated cardiomyopathy.

The efficacy of treating dilated cardiomyopathy with metoprolol was compared with that of carvedilol. Metoprolol was administered to 29 patients, and carvedilol to 62. Patients who could not be dosed with up to 40 mg daily of metoprolol or 20 mg daily of carvedilol were defined as intolerant. As well as the tolerability of these beta-blockers, the effects on left ventricular end-diastolic dimension (LVDd), fractional shortening (FS), plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) concentrations, the delayed heart and mediastinum (H/M) ratio determined from metaiodobenzylguanidine imaging were compared. Drug intolerance occurred in 24% of patients in the metoprolol group and 19% in the carvedilol group. Among the drug-tolerant patients, LVDd, FS and plasma BNP concentration improved in both groups and to the same degree. Only 25% of drug-tolerant patients in the metoprolol group had a delayed H/M ratio below 1.9 compared with 57% in the carvedilol group. Both metoprolol and carvedilol, when tolerated, improve cardiac function and neurohumoral factors to the same degree. However, carvedilol is preferable to metoprolol for patients with a low delayed H/M ratio.

An enhanced method for left ventricular volume and ejection fraction by triggered harmonic contrast echocardiography.

To elucidate the validity and reproducibility of the use of intravenous echo-contrast agent in the evaluation of left ventricular (LV) performance, we measured LV volume and ejection fraction (EF) in 42 patients with triggered harmonic contrast imaging (THCI), compared with continuous harmonic imaging without contrast agent (CHI) and with cineventriculography (CVG). In 10 of 42 patients, THCI improved LV border delineation which could not be obtained even with CHI. LV end-diastolic, end-systolic volumes and EF by both CHI and THCI correlated well with those by CVG. Although LV volumes are underestimated, THCI lessened the mean differences to about in half, compared with CHI. The observer variabilities obtained using THCI were smaller than those by CHI. These results indicate the validity of LV enhancement and the measurement of EF using THCI. We suggest that this method noninvasively provides more accurate LV systolic function with the acceptable reproducibility.

Theophylline metabolism after cardiac surgery.

The effect and metabolism of theophylline administration after cardiac surgery has never been reported. Two series of 2-hour intravenous aminophylline administrations (3 mg/kg/h) were conducted in 10 adult patients on the operative day (acute phase) and on the 4th or 5th postoperative day (recovery phase). Both blood and urine samples were collected for 24 hours after dosing. Heart rate increased in both phases, but the cardiac index increased with the decrease of diastolic blood pressure only in the acute phase (p < 0.05). Plasma concentration levels of theophylline tended to be slightly higher in the acute phase, and renal clearance increased in the recovery phase (p < 0.05). The urinary ratio of 3-methylxanthine to theophylline was significantly higher in the acute phase (p < 0.05). This suggests that cytochrome P4501A2 is partially activated rather than depressed and that N-demethylation is promoted more than hydroxylation immediately after surgery.

Recent trend of increase in proportion of low birthweight infants in Japan.

BACKGROUND: The proportion of low birthweight babies (LBW: 1500-2499 g) in Japan decreased steadily from 1950 to the 1970s. However, since then it has started to increase consistently, the reason for which has not been discussed in detail. METHODS: Trends of birthweight and the two known factors for low birthweight (maternal smoking, and pre-pregnancy weight) were analysed with vital statistics, national nutritional and smoking prevalence survey data. RESULTS: Increase in term LBW due to intrauterine growth retardation, is the major risk factor for the overall increase since the 1970s. The increase of smoking prevalence in women in their thirties started in the 1970s, while that for women in their twenties started in the 1960s. The decrease of body mass index for women in their thirties also began in the 1970s, while that for women in their twenties began in the 1960s. The ratio of delivery to mothers in their thirties to mothers in their twenties has increased more than threefold compared to the late 1970s. CONCLUSIONS: Since the 1970s increase in smoking prevalence and decrease in body mass index in young women, especially those in their thirties, appeared to be the major factors involved in the increase in LBW babies.

Intracoronary positive and negative contrast jets at a 'napkin ring' coronary stenosis: a case report.

A very short coronary stenosis is somewhat difficult to correctly evaluate by conventional coronary angiography. The demonstration of positive and negative contrast jets observed just distal to the lesion is helpful in identifying the severity of the disease causing this disorder. In the present case, intravascular ultrasound confirmed the presence of a very short stenosis and membranous disease at the site of the lesion. The presence of intracoronary contrast jets reflects the morphology and severity of disease of the membranous type, although the reason for the appearance of contrast jets with this type of lesion should be sought.

The role of histidine-114 of Ssulfolobus acidocaldarius geranylgeranyl diphosphate synthase in chain-length determination.

Sulfolobus acidocaldarius geranylgeranyl diphosphate synthase yields (all-E)-C(20) prenyl diphosphate as a final product. The three-dimensional model of the enzyme suggested that removing two bulky residues at 77 and 114 would allow additional prenyl-chain elongation. To test this, we examined several mutants with substitutions at 77 and/or 114. As a result, the mutants, F77G, F77G and H114A, F77G and H114G, H114A, and H114G gave C(30), C(45), C(50), C(30) and C(40) as the main long product, respectively. These observations indicate that histidine-114 plays a crucial role in chain-length determination along with phenylalanine-77.

Improvement in cardiac function and free fatty acid metabolism in a case of dilated cardiomyopathy with CD36 deficiency.

A 27-year-old man diagnosed as having dilated cardiomyopathy (DCM) without myocardial accumulation of 123I-beta-methyl-iodophenylpentadecanoic acid, and he was found to have type I CD36 deficiency. This abnormality of cardiac free fatty acid metabolism was also confirmed by other methods: 18F-fluoro-2-deoxyglucose positron emission tomography, measurements of myocardial respiratory quotient and cardiac fatty acid uptake. Although the type I CD36 deficiency was reconfirmed after 3 months, the abnormal free fatty acid metabolism improved after carvedilol therapy and was accompanied by improved cardiac function. Apart from a cause-and-effect relationship, carvedilol can improve cardiac function and increase free fatty acid metabolism in patients with both DCM and CD36 deficiency.

Synthesis of 1-azabicyclo[3.3.0]octane derivatives and their effects as piracetam-like nootropics.

A useful pharmaceutical intermediate, 5-nitromethyl-1-azabicyclo[3.3.0]octane (1), was prepared in one step from 1,7-dichloro-4-heptanone (4) under mild conditions. Catalytic hydrogenation of 1 over Raney Ni in the presence of sodium hydroxide afforded 5-aminomethyl-1-azabicyclo[3.3.0]octane (2) in high yield. Piracetam analogues 20-23, which were pyrrolidine derivatives involving a 1-azabicyclo[3.3.0]octane ring, were synthesized. Pharmacological tests showed that N-[(1-azabicyclo[3.3.0]octan-5-yl)methyl]-2-oxo-1-pyrrolidineacetamid e (20) improves cerebral function.