Effects of bovine milk ingestion on urinary excretion of oxypurinol and uric acid.

OBJECTIVE: Although allopurinol is a xanthine oxidase inhibitor, its overall effect may be due to the action of oxypurinol, a metabolite of allopurinol and another xanthine oxidase inhibitor, since the biological half-life of oxypurinol is longer than that of allopurinol. Oxypurinol shares a renal transport pathway with uric acid and ingestion of bovine milk increases the urinary excretion of uric acid. Therefore, we investigated whether its ingestion promotes the urinary excretion of oxypurinol. SUBJECTS/METHODS: Bovine milk (15 ml/kg body weight) was administered to 6 healthy subjects who took allopurinol (300 mg) 12 h prior to ingestion. In addition, a control experiment was performed with the same subjects using the same protocol, except for the ingestion of water instead of bovine milk. Blood and urine samples were collected before and after bovine and water ingestion. RESULTS: In the bovine milk ingestion experiment, the urinary excretion values of oxypurinol and uric acid were increased by 18% and 38%, respectively, and the fractional excretion values of oxypurinol and uric acid were increased by 20% and 40%, respectively, whereas those did not change in the control experiment. In addition, the concentration of alanine and sum of concentrations of amino acids were increased by 16% and 20%, respectively, in the bovine milk ingestion experiment. CONCLUSION: These results suggest that bovine milk ingestion promotes the urinary excretion of oxypurinol as well as uric acid by increasing amino acid concentration.

Serum CRP in patients with gout and effects of benzbromarone.

OBJECTIVE: C-reactive protein (CRP) is associated with increased risk for myocardial infarction, atherosclerosis, and peripheral artery diseases, while increased serum uric acid level is suggested to be independently associated with an increased risk of cardiovascular mortality. Accordingly, to investigate whether hyperuricemia is associated with serum CRP, we compared serum CRP levels between healthy subjects and patients with gout. In addition, we also examined whether benzbromarone has effects on serum CRP levels in patients with gout and the expression of CRP messenger RNA of CRP in the hepatoma cell line HuH7. METHODS: In the first experiment, 40 healthy males and 43 male patients with gout were enrolled, then blood samples were drawn from each after an overnight fast. In the second experiment, 42 male patients with gout were given uric acid-lowering therapy with benzbromarone. Blood samples were drawn after an overnight fast before and 1 year after beginning benzbromarone treatment. In the third experiment, the effects of benzbromarone on IL1beta-induced CRP expression were determined in HuH7 cells. RESULTS: Log serum CRP levels were not significantly different between the patients with gout and healthy subjects, while log serum CRP levels were decreased by 11% after benzbromarone treatment, as compared to the values before treatment (p < 0.01). In addition, log serum adiponectin levels were elevated by 2% after treatment (p < 0.01). Furthermore, our in vitro findings demonstrated that benzbromarone down-regulated IL1beta-stimulated CRP gene expression. CONCLUSIONS: These results suggest that hyperuricemia may not contribute to an increase in serum CRP level, while benzbromarone may have a favorable effect on CRP.

In situ XAFS study on cathode materials for lithium-ion batteries.

Ni and Co K-edge X-ray absorption spectra of LiNi0.8Co0.2O2 have been collected using in situ coin cells. To investigate the electronic and structural changes accompanied by the capacity fading during electrochemical cycling and keeping batteries at high temperatures, the cells with different cycling states and keeping conditions (temperature, time) were prepared. Upon charging the cell, the Ni and Co K absorption edge shifted towards higher energy, and the good correlation between the range of chemical shifts upon charging and the capacity of the cell was observed. From quantitative analysis of EXAFS data, it was revealed that the capacity fading is closely related to the Jahn-Teller distortion of the NiO6 octahedron.

Two small intrahepatic cholangiocarcinomas with different sonographic appearances.

We report on 2 cases of small intrahepatic (or peripheral) cholangiocarcinomas initially detected by sonography and completely resected. The lesions had a peripheral hypoechoic component and a central isoechoic or hyperechoic component. One had posterior acoustic shadowing on sonography, and the other did not. Comparison with pathologic findings in both cases indicated that severe fibrotic changes may have caused the posterior acoustic shadowing. This finding is extremely rare. We found only 1 previously reported case of cholangiocarcinoma accompanied by acoustic shadowing.

Pancreatic arteriovenous malformation presenting as cysts: Doppler sonographic diagnosis.

A 50-year-old man presented with multiple lesions resembling cysts throughout the pancreas on gray-scale sonography. Pulsatile blood flow detected within the lesions on color Doppler sonography led to the diagnosis of pancreatic arteriovenous malformation (PAVM). Most previously reported PAVMs have been described as having a poorly defined, reticular, or mosaic-like hypoechoic appearance on gray-scale sonography; the cystic appearance of the PAVM seen in our case is unusual.

Monotypic epithelioid angiomyolipoma of the liver.

AIMS: Monotypic epithelioid angiomyolipoma is a recently recognized renal tumour, which is composed purely of epithelioid cells coexpressing markers of both smooth muscle differentiation and melanogenesis (HMB45). We report here the first case of monotypic epithelioid angiomyolipoma arising in the liver. CASE DETAILS: A 30-year-old woman without tuberous sclerosis complex (TSC) was incidentally found to have a hepatic mass by ultrasonography. Grossly, the resected tumour showed a nodule-in-nodule appearance, with large areas of haemorrhagic necrosis. Microscopically, the tumour was composed of pleomorphic epithelioid cells with clear, eosinophilic cytoplasm. Neither adipocytes nor abnormal vessels were recognized in the tumour. Immunohistochemically, the tumour cells were strongly positive for HMB45 and S100 protein, focally positive for desmin, vimentin and smooth muscle actin, and negative for epithelial markers (cytokeratins, EMA). Ultrastructural analysis showed numerous dense granules with some striated ones resembling melanosomes, myofilaments and pinocytic vesicles in the cytoplasm. Molecular analysis showed no allelic loss of the TSC2 region or 12 other chromosomal regions. The patient is free of disease over 1 year after the operation. CONCLUSION: We consider that this hepatic tumour is closely related to angiomyolipoma, and a counterpart of renal monotypic epithelioid angiomyolipoma.

Pityriasis versicolor with a unique clinical appearance.

We experienced an atypical case of pityriasis versicolor with a unique clinical appearance and undescribed mycological features. Although Malassezia sp. was cultured from the keratotic material, the fungal elements observed in the material were not readily identified as Malassezia. The diagnosis was established with the aid of immunohistochemical and ultrastructural studies with the aetiological agent being identified as M. globosa.

Effect of the oral administration of Lactobacillus brevis subsp. coagulans on interferon-alpha producing capacity in humans.

OBJECTIVE: This study was designed to determine whether the oral administration of Lactobacillus brevis subsp. coagulans modulates immunological responses in human subjects, and whether there are differences in response between live and heat-treated preparations. METHODS: The effect of the oral administration of Lactobacillus brevis subsp. coagulans (Labre) for 4 weeks on the interferon-alpha (IFN-alpha) producing capacity of apparently healthy subjects was evaluated. Sixty volunteers were divided into five groups for the determination of virus-induced IFN-alpha production in response to various doses of live and to heat-killed Labre. 2-5A synthetase activity was measured to detect trace amounts of IFN production. Routine blood tests were also performed to determine the state of health of the subjects involved in this study and to test any side effects of Labre treatment. RESULTS: The oral administration of live Labre showed a statistically significant increase in IFN-alpha production at 2 weeks (p < 0.05) and at 4 weeks (p < 0.05) in the group receiving 600 million bacteria/day and at 4 weeks (p < 0.05) in the group receiving 300 million bacteria/day. In particular, IFN-alpha production in those with initially low levels rose significantly when either 300 million or 600 million bacteria/day were ingested. Consumption of heat-killed Labre 300 million bacteria/day did not result in a statistically significant change in IFN-alpha production. The level of 2-5A synthetase activity remained the same in the control and experimental groups. CONCLUSIONS: Oral administration of live Labre significantly increased IFN-alpha production in a dose-dependent manner. Labre intake tended to be most beneficial in subjects with initially low levels of IFN-alpha production. Heat-treated Labre did not elicit a response similar to that of the live bacteria.

Endogenous endothelin-1 mediates cardiac hypertrophy and switching of myosin heavy chain gene expression in rat ventricular myocardium.

OBJECTIVES: We investigated the role of endogenous endothelin-1 in the development of cardiac hypertrophy in vivo under pressure overload conditions. BACKGROUND: Endothelin-1, a potent vasoconstrictor peptide, has recently been shown to act as a growth factor of myocardial cells in culture. METHODS: We examined the effect of an endothelin-A receptor antagonist (FR139317) on the development of right ventricular hypertrophy in rats with monocrotaline-induced pulmonary hypertension. Three groups of rats were studied: those given monocrotaline alone or monocrotaline plus FR139317 and those given vehicle alone (control group). RESULTS: The ratio of right ventricular systolic pressure to aortic systolic pressure was similarly elevated in rats treated with monocrotaline and monocrotaline plus FR139317. The right ventricular/left ventricular weight ratio was increased in monocrotaline-treated rats but lower in rats treated with monocrotaline plus FR139317 than in those treated with monocrotaline alone (p < 0.01). As a biochemical marker of hypertrophy, the isoform ratio of beta-myosin heavy chain protein was determined for the right ventricular tissue samples. This ratio was increased in all monocrotaline-treated rats but was lower (p < 0.01) in rats given monocrotaline plus FR139317 than in those given monocrotaline alone. The isoform ratio of beta-myosin heavy chain messenger ribonucleic acid quantitated by S1 nuclease mapping also was lower (p < 0.025) in rats receiving monocrotaline plus FR139317 than in those receiving monocrotaline alone. CONCLUSIONS: These data suggest that blocking the action of endothelin-1 with a receptor antagonist ameliorates cardiac hypertrophy in this model system, and that this action is not mediated by ameliorating hemodynamic changes.

Sebaceous epithelioma with sweat gland differentiation.

We examined a neoplasm of > 10 years' duration on the head of a woman. Light microscopically, the neoplasm was composed of multiple epithelial lobules in the dermis. The islands were mainly made up of basaloid cells and sebaceous cells; the latter cells were focally grouped in the lobules. Neither a palisade arrangement of peripheral cells nor the formation of peritumoral clefts were seen. Ductal spaces were scattered in the lobules and their luminal surfaces showed keratinization. Furthermore, in the peripheral parts of some lobules, there were sweat-gland-like structures. Immunohistochemically, most of the lobules were shown to have stratified squamous epithelium-type keratins, while the sweat-gland-like structures were shown to have simple epithelium-type keratins and stained positive for carcinoembryonic antigen. Ultrastructurally, many cells had lipid formation in their cytoplasm, and some cells formed luminal walls keratinizing without microvilli and keratohyaline granules. Although most of this neoplasm showed sebaceous differentiation, it partially differentiated to secretory cells of sweat gland apparatus.

[Convulsive seizure after craniotomy--comparison of isoflurane anesthesia and sevoflurane anesthesia].

The incidence of postoperative convulsive seizure was compared retrospectively during either isoflurane or sevoflurane anesthesia in patients after craniotomy. Overall, 5 of a total of 125 patients suffered convulsive seizures after craniotomy: 2 (4%) of 45 patients with isoflurane anesthesia and 3 (4%) of 80 patients with sevoflurane anesthesia. No significant differences were observed between these two groups. The duration of anesthesia and duration of the MAC.h were similar between these two groups. The occurrence of postoperative convulsive seizure was not related with the inhalational anesthetic agents, the underlying disorders and patient characteristics. It is suggested that either isoflurane or sevoflurane anesthesia in neurosurgical patients may have no specific relationship with the postoperative convulsive seizures.

[How should we treat intestinal ischemia?--II: Effects of pentoxifylline, glucagon and prostaglandin E1].

It is important to repair or ameliorate the intestinal ischemia in critically ill patients. Recent study of our suggests the superiority of dobutamine, but not dopamine, in improving the intestinal oxygenation. In this study we examined the effects of pentoxifylline (PF), glucagon (GL) and prostaglandin E1 (PGE1) during reduced blood flow of the superior mesenteric artery (SMA) in 20 anesthetized dogs. As an index of the intestinal oxygenation, tonometrically measured intestinal intramural pH (pHi) was used. A tonometer was inserted into the midjejunum through enterotomy. The SMA blood flow was measured by a transit-time flow meter. A vascular screw clamp for blood flow reduction was placed around the origin of the SMA, proximal to the flow probe. The SMA blood flow was adjusted to 70% of baseline for three hours. After two hours of decreased blood flow, pHi dropped significantly from baseline. Then, either PF (20 mg.kg-1.min-1 over 10 min, followed by 0.1 mg.kg-1.min-1), GL (1 microgram.kg-1.min-1) or PGE1 (0.05 and 0.5 microgram.kg-1.min-1) was infused intravenously for one hour. With infusions of GL and large dose of PGE1, pHi tended to decrease further, although GL increased the cardiac output. Small dose of PGE1 had no significant effect on pHi. PF treatment showed beneficial effects not only on the cardiac output and the SMA blood flow, but also on pHi. We conclude that PF therapy may restore the intestinal microvascular blood flow. Further study of the effects of PF on tissue oxygenation and blood rheology is warranted.

[How should we treat intestinal ischemia?--1: Effects of dobutamine and dopamine].

Intestinal mucosal ischemia is one of the earliest manifestations of impaired core tissue perfusion in critically ill patients. The aim of this study was to investigate the effects of dobutamine and dopamine on intestinal ischemia in ten anesthetized dogs. Intestinal intramural pH (pHi) by tonometry is an early reliable marker of assessing the adequacy of tissue oxygenation. A tonometer was inserted into the midjejunum through enterotomy. The superior mesenteric artery (SMA) blood flow was measured by a transit-time ultrasonic flowmeter. A vascular screw clamp for blood flow reduction was placed at the origin of the SMA, proximal to the flow probe. The SMA blood flow was maintained at 70% of baseline flow for three hours. After two hours of decreased blood flow, intravenous dobutamine or dopamine was infused at a rate of 5 micrograms.kg-1.min-1 for one hour. The pHi fell significantly from 7.16 +/- 0.04 to 7.08 +/- 0.04 in dobutamine group, and from 7.18 +/- 0.04 to 7.06 +/- 0.05 in dopamine group two hours after induction of intestinal ischemia. Treatments with dobutamine and dopamine increased the SMA blood flow to near baseline levels. Dobutamine caused a significant increase in pHi to 7.11 +/- 0.04. On the contrary, dopamine tended to decrease pHi further to 7.01 +/- 0.09. These results suggest that dobutamine may improve intestinal tissue oxygenation. However, dopamine even at lower doses, may induce constriction of the intestinal mucosal arterioles.

Changes in muscle and liver lactate concentrations after endotoxin infusion in rats.

The interstitial lactate concentration in rat skeletal muscle and liver was measured using a microdialysis method during the early stage of endotoxemia and during lactic acid infusion. The lactate concentration in the muscle and liver interstitium never exceeded the blood lactate concentration throughout the 180 min period after endotoxin administration. The present findings also showed that the muscle and liver interstitial lactate concentration gradually increased in endotoxin-infused animals compared to that in lactic-acid infused animals, although the blood lactate concentration in lactic acid-infused animals was the same as that in endotoxin-infused animals. These findings suggest that the skeletal muscle and liver may consume lactate in an endotoxemic condition. However, the capacity of lactate consumption in the skeletal muscle might gradually decrease after endotoxin administration, although that in liver might be well preserved.

Effects of glucose load on brain extracellular lactate concentration in conscious rats using a microdialysis technique.

Changes in the brain lactate concentration in cerebral extracellular fluid (ECF) during intravenous infusion of glucose and local administration of glucose were investigated in adult, conscious, unrestrained rats, with a microdialysis probe in the posterior hippocampus. The rats were infused intravenously with either 25% sucrose solution or 25% glucose solution at a rate of 16.6 microliters.min-1.100 g-1 for three hours. The blood glucose concentration reached 17.0 +/- 2.6 mM at the end of the glucose infusion, and brain ECF glucose showed a parallel change with the blood glucose concentration and increased to 2.37 +/- 0.30 mM. However, blood and brain ECF glucose concentrations did not change in animals infused with the sucrose solution. On the other hand, the blood lactate concentration in the glucose-infused group also increased from 0.93 +/- 0.18 mM to 2.85 +/- 0.39 mM at the end of the glucose infusion, which was significantly higher than that measured in the sucrose-infused group. The blood lactate level in the glucose-infused group returned to the basal level by the end of the experiment. Brain ECF lactate concentrations increased from 1.21 +/- 0.06 mM to 1.69 +/- 0.11 mM in glucose-infused animals, but did not change in the sucrose-infused animals. The brain ECF lactate concentration showed a positive correlation with the brain ECF glucose concentration in glucose-infused animals. Another group of rats was administered glucose locally for 90 min after substitution of artificial cerebrospinal fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

[Gastrointestinal mucosal ischemia in hemorrhagic shock--measurement with a tonometer].

Splanchnic ischemia produces the most rapid progression of mucosal injury. A reliable method for monitoring the adequacy of tissue oxygenation in the mucosal layer would be clinically valuable. In this study, we investigated the potential value of tonometric intestinal intramucosal pH (pHi) monitoring during hemorrhagic shock in twelve anesthetized dogs. The tonometer consists of a sampling tube with a silicone balloon attached to the tip that is freely permeable to CO2. Intestinal pHi was calculated by the Henderson-Hasselbalch equation and measurements of the PCO2 of the normal saline within the balloon and arterial bicarbonate. The tonometer was placed in the midpart of the small intestine through a small enterotomy. Arterial blood was removed into a heparinized bag to achieve a mean arterial blood pressure of 50-60 mmHg for two hours. Baseline pHi level was 7.28 +/- 0.02 (mean +/- SE). Following hemorrhage, pHi continued to decrease significantly during the experiments down to 6.94 +/- 0.05 at one hour and 6.82 +/- 0.12 at two hours. By treatment with an intravenous infusion of dopamine at a rate of 3 micrograms.kg-1.min-1 started at one hour after hemorrhage, pHi did not returned to baseline levels. Monitoring pHi in the small intestine using tonometer could be a useful technique to provide early detection of insufficient mucosal blood flow.