Search

We investigated whether the difference of insulin effect existed or not when insulin was administered at different times; just before the light phase (am 6:00) (L-NPH-DM) or just before the dark phase (pm 6:00) (D-NPH-DM) in streptozotocin (60 mg/kg, ip)-induced diabetic rats. Following results were obtained 7 days after STZ administration. Body weight: A significant increase compared to (D-NPH-DM) group was observed in (L-NPH-DM) group. Food intake: Food intake gradually increased after administration of STZ. A significant decrease compared to (saline-DM) group was observed only in the (L-NPH-DM) group. Total lipid content in the liver: A significant increase compared to (saline-control) group was seen in both the (D-saline-DM) and (L-saline-DM) group. In addition, a significant decrease compared to (D-NPH-DM) was observed in the (L-NPH-DM) group. Changes in blood glucose: Different patterns in decrease of blood glucose was observed between (D-NPH-DM) and (L-NPH-DM) groups. In conclusion, the present study demonstrates for the first time that there are differences of insulin effects on body weight, food intake, total lipid content in the liver and blood glucose level with insulin administration time.

Changes in hypothalamic monoamine metabolism were investigated in the genetically obese yellow (Ay/a) mouse. At the age of 6 weeks when there was no difference in body weight between black (a/a) and yellow (Ay/a) mice, the contents of norepinephrine (NE), dopamine (DA) and their main metabolites (MHPG, DOPAC) were already significantly reduced in yellow (Ay/a) mice. Reduction of 5-hydroxytryptamine (5-HT) level and an increasing 5-HIAA/5-HT ratio has been observed. When a significant increase in body weight in the yellow (Ay/a) mouse at the age of 12 weeks was present, both NE and DA contents have been increased in the hypothalamus of the obese mouse. MHPG level was lower than in the lean mouse, resulting in an increase of MHPG/NE ratio. The present study suggests that the observed reduction in hypothalamic NE and DA metabolism might be involved in the development of overweight gain in the yellow (Ay/a) mouse.

1. Inter-breed morphological comparisons were made among 11 breeds of Japanese native chickens (Gifujidori, Hinaidori, Shokoku, Totenko, Tomaru, Satsumadori, Shamo, Koshamo, Koeyoshi, Chabo and Nagoya), White Leghorn, broiler chickens (Chunky) and red junglefowl collected in the Philippines, based on results of direct measurements and analysis by computer vision techniques of the skull. 2. Analysis of direct measurements identified two groups of chicken: a small type that included the Chabo, Koshamo, red junglefowl, Gifujidori and Shokoku and a large type that included the remaining breeds studied. These groupings were made based on size determined both in the first (PC1) and second principal component (PC2). The greatest length of the cranium and condylobasal length greatly contributed to the morphological differences between these two groups. 3. Analysis by computer vision techniques, however, identified three groups: the Bantam group (which includes red junglefowl), Shokoku group and Shamo group. White Leghorn clustered within the Shokoku group while the broiler chicken belonged to the Shamo group. The region around the junction of the neural cranium and the visceral cranium contributed greatly to the morphological differences among breeds, both in the PC1 and PC2.

Objective: We recently reported that eating glutinous brown rice (GBR) for 1 day improved the whole-day glucose profile and postprandial plasma glucose level compared with eating white rice (WR) or standard brown rice. However, it was unknown whether eating GBR could maintain improvement of glycemic control for a longer period. Therefore, we evaluated the effect of GBR intake for 8 weeks on glycemic control in outpatients with diabetes mellitus. Methods: This was an open-label randomized crossover study in outpatients with type 2 diabetes. Among the 18 subjects registered in this study, 2 were excluded from analysis. After a 1-week observation period while eating WR twice a day, the patients were randomly assigned to two groups. One group ate GBR as a staple food twice a day for 8 weeks and then switched to WR for the next 8 weeks, while the other group ate WR first and then switched to GBR. A mixed meal tolerance test was performed at baseline and after 8 and 16 weeks of dietary intervention to evaluate plasma glucose and serum C-peptide. Results: None of the subjects failed to complete the study because of disliking the taste of GBR. Hemoglobin A1c (7.5–7.2%, P=0.014) and glycoalbumin (20.4–19.4%, P=0.029) both decreased significantly when the patients were eating GBR. Additionally, the 30-min postprandial plasma glucose level (194–172 mg dl−1, P=0.031) and the incremental area under the concentration vs time curve of serum C-peptide (31.3–22.1 ng min ml−1, P=0.023) during the mixed meal tolerance test were also decreased significantly by intake of GBR. In contrast, there were no changes of glycemic control during the WR period. Conclusions: We confirmed that GBR was well tolerated for 8 weeks and improved glycemic control in patients with type 2 diabetes.

Few studies have tried to characterize the efficacy of parenteral support of critically ill infants during short period of intensive care. We studied seventeen infants during five days of total parenteral hyperalimentation. Subsequently, according to the clinical conditions, the patients received nutritional support by parenteral, enteral route or both up to the 10th day. Evaluations were performed on the 1st, 5th, and 10th days. These included: clinical data (food intake and anthropometric measurements), haematological data (lymphocyte count), biochemical tests (albumin, transferrin, fibronectin, prealbumin, retinol-binding protein) and hormone assays (cortisol, insulin, glucagon). Anthropometric measurements revealed no significant difference between the first and second evaluations. Serum albumin and transferrin did not change significantly, but mean values of fibronectin (8.9 to 16 mg/dL), prealbumin (7.7 to 18 mg/dL), and retinol-binding protein (2.4 to 3.7 mg/dL) increased significantly (p < 0.05) from the 1st to the 10th day. The hormonal study showed no difference for insulin, glucagon, and cortisol when the three evaluations were compared. The mean value of the glucose/insulin ratio was of 25.7 in the 1st day and 15.5 in the 5th day, revealing a transitory supression of this hormone. Cortisol showed values above normal in the beginning of the study. We conclude that the anthropometric parameters were not useful due to the short time of the study; serum proteins, fibronectin, prealbumin, and retinol-binding protein were very sensitive indicators of nutritional status, and an elevated glucose/insulin ratio, associated with a slight tendency for increased cortisol levels suggest hypercatabolic state. The critically ill patient can benefit from an early metabolic support. A avaliação nutricional seqüencial é muito importante para a adequação e monitoramento da terapia nutricional. Raros estudos caracterizaram a eficácia da terapia nutricional parenteral em lactentes gravemente doentes. Foram estudados 17 lactentes submetidos à terapia nutricional parenteral total por cinco dias. Posteriormente, de acordo com as condições clínicas, os pacientes recebiam terapia nutricional parenteral, enteral ou mista até o décimo dia de internação. As avaliações nutricionais eram realizadas no primeiro, quinto e décimo dias e constavam de: dados clínicos ( história alimentar e medidas antropométricas), dado hematológico (contagem de linfócitos), testes bioquímicos (albumina, transferrina, fibronectina, pré-albumina e proteína ligada ao retinol) e dosagens hormonais (cortisol, relação glicemia/insulina, glucagon). As medidas antropométricas não revelaram diferença significante entre a primeira e seguunda avaliações. Os níveis de albumina e transferrina não se modificaram significativamente, mas os valores médios de fibronectina (8.9 a 16mg/dL), pré-albumina (7.7 a 18mg/dL) e proteína ligada ao retinol (2.4 a 3.7mg/dL) aumentaram significativamente (p < 0.05) do primeiro ao décimo dia. O estudo hormonal não revelou diferenças para insulina, glucagon e cortisol nas três comparações. O valor médio da relação glicemia/insulina foi de 25.7 no primeiro dia e 15.5 no quinto dia, revelando supressão transitória deste hormônio. O cortisol mostrou valores acima do normal no início do estudo. Neste estudo concluiu-se que os parâmetros antropométricos não foram úteis no curto período de avaliação. As proteínas viscerais foram de boa sensibilidade e a relação glicemia/insulina aumentada, associada com uma tendência de elevação do cortisol, sugerem estado hipercatabólico. Os lactentes gravemente doentes podem se beneficiar de uma terapia nutricional precoce.

Leptin, ob gene product, inhibits feeding behavior and stimulates energy expenditure in rodents. Corticotropin-releasing hormone (CRH) and neuropeptide Y (NPY), which act in the hypothalamus to influence energy homeostasis, may mediate the anorexic effect of leptin. The present studies were undertaken to examine the possible involvement of hypothalamic CRH in the anorexigenic action of leptin in male Wistar rats. Recombinant leptin (2 microg/rat), microinjected into the third ventricle, inhibited food intake at 2 h by 33.3% (P < 0.01) in rats that were deprived of food for 18 h. The intracerebroventricular injection of 2 microg leptin also increased hypothalamic CRH content (P < 0.05) at 2 h after its administration. Simultaneous intracerebroventricular administration of 5 microg/rat alpha-helical CRH 9-41 (alpha-hCRH), a CRH antagonist, with 2 microg/rat leptin attenuated the anorexic effect of leptin by 2 h. In contrast, single intracerebroventricular injection of alpha-hCRH did not affect food consumption in food-deprived rats. These results implicate hypothalamic CRH as an important mediator of the anorexic effect of leptin in food-deprived rats.

Near-normalization of glycemia reduces the risks of chronic diabetic complications but increases the risk of serious hypoglycemia. Hypoglycemia can impair neuronal function in the brain and diminish awareness of subsequent hypoglycemic episodes, yet little is known about how neurons adapt to hypoglycemia. This study tests the hypothesis that isoform-specific alterations in brain glucose transport proteins occur in response to chronic hypoglycemia. To study this, groups of rats were injected with approximately 25 U/kg ultralente insulin daily at 1700 for 8 days to maintain hypoglycemia. Vascular-free and microvessel membrane fractions from brain were prepared for immunoblot analysis of GLUT-1 and GLUT-3 by use of isoform-specific antisera. Insulin treatment reduced blood glucose levels from 4.0 +/- 0.1 (vehicle-injected controls) to 1.7 +/- 0.1 mmol/l on day 8 (P < 0.001) and increased GLUT-3 protein expression (175.6% of control; P < 0.05). Microvascular GLUT-1 (55 kDa) tended to increase (195.6% of controls; P = 0.08) variably, whereas nonvascular GLUT-1 (45 kDa) was unchanged. We conclude that neuronal glucose transport protein (GLUT-3) expression adapts to chronic hypoglycemia. This adaptation may spare neuronal energy metabolism but could dampen neuronal signaling of glucose deprivation.

Excessive daytime sleepiness (EDS) is a common sleep disorder in patients with Parkinson disease (PD). Non-ergot dopamine agonists increase the risk of unanticipated sleep episodes. We aimed to assess the influence of renal function on EDS in patients with PD.Sixty-two patients treated with ropinirole or pramipexole were recruited for this study. We evaluated the historical and clinical characteristics including the motor symptom rating scales, Epworth Sleepiness Scale (ESS), and estimated glomerular filtration rate (eGFR). An ESS score of 10 or greater was defined as EDS. Participants with eGFR60 ml/min/1.73 m(2) were determined to have chronic kidney disease (CKD). Multiple logistic regression analysis was performed to determine the predictive factors of EDS.Chronic kidney disease was found to be a significant predictive factor for EDS in all patients (P = 0.014). We observed a negative correlation between the severity of daytime sleepiness and renal function in patients treated with pramipexole alone (r(s) = -0.637, P0.001).Chronic kidney disease may be a risk factor for EDS, especially in patients treated with pramipexole, which is directly excreted in the urine.

Pancreaticopleural fistulas are a rare complication of acute or chronic pancreatitis, and are usually treated by surgery. We report three patients whose pancreaticopleural fistulas were successfully treated by endoscopic retrograde cholangiopancreatography and drainage (stenting, nasopancreatic drainage). In one patient a pancreatic pseudocyst persisted despite successful initial closure of the leak using this method and, as it was also suspected to be infected, additional drainage of the pseudocyst was required. Endotherapy of pancreaticopleural fistulas could obviate the need for surgery when conventional medical treatment has failed in this condition.

An intussusception-type antireflux valve (ARV) has been introduced to prevent postoperative ascending cholangitis in the management of biliary atresia (BA). We investigated the characteristics of cholangitis in the management of BA using the ARV in 38 patients who had undergone an operation at our institution; 29 underwent ARV construction at the same time as portenterostomy (PEO) or hepaticojejunostomy. One patient underwent ARV construction for refractory cholangitis with cystic dilatation of the intrahepatic bile ducts (CDIB) long after the PEO. Five of 29 patients who had ARV construction developed CDIB complicated by severe, refractory cholangitis. One or two episodes of mild cholangitis were observed in 5 (20.8%) of 24 patients who did not show CDIB. An ARV created for postoperative recurrent cholangitis associated with CDIB was ineffective. Preoperative cholangitis associated with a type I choledochal cyst and CDIB was observed in 1 patient. In conclusion, the ARV was effective in preventing refractory cholangitis without CDIB, but ineffective in preventing cholangitis with CDIB. Our findings suggest that CDIB resulting from the ongoing process of BA could be a potential target of bacterial infection through other routes than bilioenteric reflux.

We investigated whether the sex of hypertensive parents mediates determination of blood pressure in their normotensive offspring. We analyzed medical checkup data from 7279 Japanese university students. Six hundred and forty-one students had one hypertensive parent with or without hypertensive grandparents, and 609 of these were available for the present analysis. Blood pressure levels in the students with one hypertensive parent were within the normotensive range; however, the blood pressure levels were higher than those in students without hypertensive relatives, and lower than those in students with two hypertensive parents. In the students with one hypertensive parent, systolic blood pressure levels were significantly higher in the male than in the female students. However, the sex of the hypertensive parent did not affect the blood pressure values of their offspring. Multivariate analyses revealed that body mass index was an independent predictor of systolic blood pressure solely in male students with a hypertensive father, but not in male students with a hypertensive mother. In female students with one hypertensive parent, body mass index was irrelevant to the determination of blood pressure. These findings suggest that different mechanisms determine blood pressure in the offspring of hypertensive parents, and that blood pressure determination mediated by body mass index in male students is linked to hypertensive Y chromosome.

Azithromycin (AZM) is a new oral macrolide antibiotic drug. AZM either in 10% fine granules form or in 100 mg capsule form was studied for its pharmacokinetics and treatment efficacy in pediatric patients with various infections. 1. Pharmacokinetics. Plasma and urine samples were collected from four patients with pharyngitis and post-dosing drug levels were determined. The drug was given once daily at 10 mg/kg body weight for 3 days. The drug concentrations found in plasma at 96 hours after the first dosing (48 hours after the final dosing) lay in a range of 0.02 and 0.04 microgram/ml and in urine at 120 hours after the first dosing (72 hours after the final dosing) in a range between 3.2 and 7.7 micrograms/ml. AZM was found in two patients but no effect was observed on blood levels of theophylline determined between 48 and 96 hours after the first dosing in the treatment of underlying bronchial asthma. 2. Clinical study results. Clinical studies of AZM was carried out in 25 pediatric patients with bacterial infections that mainly affected the respiratory tract. The patients received either 10% fine granules at 10 or 20 mg/ kg body weight or 100 mg capsules at 10 mg/kg body weight once daily over 3 to 6 days. The drug was found markedly effective in six patients, moderately effective in thirteen patients, while the investigators could not assess the drug efficacy in six patients. Although no side effect was reported in the study, two patients experienced slight decrease in WBC.

We analysed blood pressure (BP) and various parameters related to glucose metabolism in 10,867 Japanese university students aged 19.22 +/- 0.01 years, and investigated the relationship between the subject's own BP and hypertension in close relatives. After 2 years we also examined a subset of these students enrolled in 1993. BP levels in subjects having hypertensive parents were normotensive, but significantly higher than those in subjects without hypertensive relatives or only with hypertensive grandparents. The close the genetic relationship was, the higher the subject's own BP levels. In subjects with hypertensive parents, the subject's own mean BP levels correlated significantly with the subject's own body mass indices. This correlation was much weaker in subjects without hypertensive relatives and those having only second degree relatives with hypertension. In addition, the BP levels in the offspring of hypertensive parents correlated with glutamyl-oxaloacetic transaminase. In the follow-up study in 1995, the correlation between BP levels and body mass index (BMI) was observed in this subgroup. Moreover, the subjects with hypertensive parents tended to have a higher plasma insulin level than those without hypertensive relatives. It is suggested that BP is more likely to be determined by BMI in the individuals with a genetic predisposition to hypertension.

We report the case of a 38-year-old man who developed fatal, systemic amyloidosis following ankylosing spondylitis. He was admitted for symptoms of congestive heart failure. Based on parotid gland biopsy and echocardiography, he was diagnosed as having systemic amyloidosis following active ankylosing spondylitis. However, the clinical course was rapidly progressive and eventually the patient died of acute necrotizing pancreatitis. The association has been reported thus far in a limited number of cases worldwide. The literature has featured localized lesions and a benign clinical course of the amyloidosis. This case, the first report from Japan, indicates that the amyloidosis associated with ankylosing spondylitis might exhibit a rapidly progressive clinical course, thereby suggesting that in such a case, meticulous treatment is required.

SY5555 is a new oral penem antibiotic. Pharmacokinetic and clinical studies using SY5555 dry syrup (powder which is dissolved before use) were performed in pediatric patients. 1. Pharmacokinetic investigation Peak plasma concentrations of SY5555 after dose of 5 mg/kg, 10 mg/kg and 15 mg/kg were, respectively, 1.58 +/- 0.37 micrograms/ml, 2.78 +/- 0.54 micrograms/ml and 5.28 micrograms/ml at 1 hour. The average half-life with 5 mg/kg administration was 0.94 +/- 0.05 hours, that with 10 mg/kg was 1.46 +/- 0.31 hours and that with 15 mg/kg was 0.88 hours. 2. Clinical investigation Enrolled in the study were 15 patients including 5 with acute otitis media, 5 with urinary tract infections and 1 each with pharyngitis, tonsillitis, bronchitis, pneumonia and subcutaneous abscess. Responses were excellent in 4 patients, good in 8 patients, fair in 2 patients and poor in 1 patient. In the assessment of the bacteriological efficacy, 8 out of 10 strains of organism identified previous to treatment were eradicated and 2 strains were unchanged, hence the eradication rate was 80.0%. 3. No adverse reactions attributable to the drug were observed and good drug compliance were obtained. From the above results, it has been concluded that SY5555 is a highly effective and safe agent for mild to moderate respiratory and urinary tract infections in children.

To investigate whether and how renin-angiotensin inhibition attenuates renal injury seen in salt-induced hypertension in Dahl salt-sensitive (Dahl-S) rats.Dahl-S rats fed a high-salt (4% sodium chloride) diet for 6 weeks were treated with the angiotensin converting enzyme (ACE) inhibitor alacepril or the angiotensin receptor antagonist losartan for 4 weeks. Functional and morphological alterations in the kidney were investigated.Alacepril decreased systolic blood pressure (SBP). This SBP reduction was associated with the attenuation of cardiac and aortic wall hypertrophy and that of proteinuria and urinary N-acetyl-beta-D-glucosaminidase excretion. Kidney injuries, e.g. glomerular, arterial and tubular damage, were improved with alacepril treatment. Losartan decreased SBP to the same extent as alacepril, but neither renal function nor morphological structure was improved as was the case with alacepril. The response of the renal eicosanoid system to alacepril was inadequate, but cyclic GMP excretion, an indicator of nitric oxide formation, was significantly enhanced and lipid peroxidation in the kidney was decreased.The beneficial effects of ACE inhibition on the renal injury in Dahl-S rats outrange those induced by the receptor antagonism. This might be due to multiple factors including an increased vasodepressor eicosanoid system, enhanced nitric oxide formation and possible inhibition of oxygen radical generation in the injured renal tissues.

Accumulating evidence indicates that the activation of cellular oncogenes is a cause of some human cancers. ErbB-1, erbB-2 and abl oncogenes encoding tyrosine kinases, ras oncogenes encoding GTP binding proteins and myc oncogenes whose functions are not well understood are some examples. Therefore, agents which inhibit the activity of these oncogene products may provide new means to overcome certain human tumors. Herbimycin A and tyrphostins have been found and developed as inhibitors of tyrosine kinases and the effectiveness of these agents against tumors of Ph1-positive leukemia (CML, ALL) or squamous cell carcinomas has been reported. Although specific inhibitors of ras or myc oncogene products have not yet been described, recent studies on the processing of Ras proteins toward the cell membrane provide a strategy to search for inhibitors of ras functions.

Progression of renal insufficiency was evaluated in partially nephrectomized Sprague-Dawley rats at the age of 10 weeks, fed on the low (6%), usual (20%), and high (36%) protein diet (group 6C, 20C, and 36C). Effects of oral adsorbent AST-120 on these experimental uremic models were also examined (group 6A, 20A, 36A). All the rats underwent paired feeding, and survived during the experimental period of 3 weeks. GFR (inulin clearance) and RPF (para-amino hippurate clearance), as well as Ccr was measured before the sacrifice. Initial serum creatinine and Ccr were 1.7 mg/dl and 0.27 ml/min. The rats of group 36C showed progressive elevation of serum creatinine level and decrease in Ccr. At the end of the study, GFR was significantly lower in group 36C than in group 6C and 20C (0.19, 0.68, 0.87 ml/min respectively). Significant elevation of filtration fraction in group 36C suggested that the decrease in GFR mainly resulted from low RPF. Even in group 36C, no glomerular sclerosis was histologically demonstrated in the remnant kidney, and the mean planar area of the remnant glomeruli was significantly small, which might reflect low RPF. Tubulo-interstitial changes like dilatation of the urinary space and tubular epithelial flattening were prominent in group 36C. Beneficial effect of AST-120 was obvious in high protein diet groups. GFR and RPF were rather well preserved in group 36A (0.36 and 0.78 ml/min) with normal filtration fraction. Tubulo-interstitial damage was evidently mild in group 36A. These data suggested the presence of some humoral factors, which can be adsorbed by AST-120 in gastrointestinal tract, and responsible for the deterioration of renal function and tubulo-interstitial damage induced by high protein diet in the uremic condition. Besides hyperfiltration and glomerular hypertrophy, such humoral factors as suggested in this study may contribute to the progression of chronic renal failure to some extent.

Evidence is accumulating that adrenal steroids may be involved in the metabolic effects of cytokines. We evaluated the possible involvement of glucocorticoids in the inhibition of pancreatic insulin secretion by interleukin-1β (IL-1β), one of the cytokines produced by inflammatory cells. In the first group of experiments, adrenalectomized rats showed a significant reduction in basal and glucose (0·5 g/kg, i.v.)-stimulated immunoreactive insulin (IRI) levels after injection of IL-1β (1·0 μg/kg), but intact rats did not. Pretreatment with IL-1β increased plasma glucose levels 2 and 15 min after an i.v. bolus of glucose in adrenalectomized rats. In the second group of experiments, dexamethasone supplement (0·1 mg/kg) given to adrenalectomized rats cancelled the reduction in plasma glucose levels by IL-1β, and rats treated with 1·0 mg dexamethasone/kg showed a significant increase in basal IRI levels and enhanced serum IRI levels after IL-1β injection. However, 1·0 mg deoxycorticosterone/kg given daily for 7 days failed to cancel the effect of IL-1β on the reduction of serum IRI levels, although it attenuated the weight loss after adrenalectomy. The data suggested that withdrawal of glucocorticoids after adrenalectomy potentiates the effect of IL-1β on the reduction of serum IRI levels. Glucocorticoids may have a protective action against the reduction of serum IRI levels by IL-1β. Journal of Endocrinology (1992) 132, 419–423

We investigated a possible alteration in the ability of neutrophils to produce active oxygen species in streptozotocin (STZ)-induced diabetic rats. The production of superoxide of the neutrophils was assessed by luminol-dependent chemiluminescence (LDCL) after the stimulation by opsonized zymosan. Four days after STZ (60 mg/kg, ip) injection, blood glucose level increased by 399 +/- 9 mg/dl and the LDCL activity was significantly reduced in diabetic rats (control group: 5.12 +/- 1.53 KC/min2/10(6) cells, STZ group: 1.10 +/- 0.07 KC/min2/10(6) cells, p less than 0.01). At Day 17, blood glucose level was maintained high (598 +/- 8 mg/dl) and the LDCL activity (1.01 +/- 0.39 KC/min2/10(6) cells) was almost at the same level as that of diabetic rats at Day 4. Subcutaneous injection of insulin for 10 consecutive days increased the LDCL activity of diabetic rats in a dose-dependent manner (vehicle: 0.82 +/- 0.27 KC/min2/10(6) cells, 0.04 U/day: 1.61 +/- 0.09 KC/min2/10(6) cells, 0.40 U/day: 1.99 +/- 0.47 KC/min2/10(6) cells, 4.00 U/day: 3.33 +/- 0.43 KC/min2/10(6) cells). The data obtained herein indicate that an increased susceptibility to bacterial infection in diabetic rats results from impaired neutrophil function to produce active oxygen species.

We determined a protective action of probucol (4,4'-[isopropylidenedithio]bis[2,6-di-tert-butylphenol]) on the reduction of serum immunoreactive insulin (IRI) levels by recombinant human interleukin-1 beta (IL-1) in adrenalectomized rats. IL-1 reduced the serum IRI levels 4 h after injection in rats fed a standard diet. However, IL-1 failed to inhibit serum IRI levels in rats fed a diet containing 1% probucol. In contrast, IL-1 decreased plasma glucose levels in both groups. Although IL-1 reduced plasma prostaglandin (PG) E2 levels in standard diet-fed rats, IL-1 did not affect plasma PGE2 levels in the animals fed the probucol-containing diet. The present study suggested that the free radical scavenger action of probucol can block the IL-1 effect on serum IRI levels.

In order to evaluate the direct or indirect effect of AST-120 on chronic renal failure (CRF) in rats, histological and electron microscopical examinations were performed. A total of 30 Sprague-Dawley rats (aged 11 weeks and weighing 226 to 229 gm) with CRF induced by 5/6 nephrectomy were prepared. Rats were fed by a commercial diet (CE-2, Japan Kurea) and were divided into two groups: A (16 rats) and B (14 rats). AST-120 (5% content) was only administered to group B. After two months, kidneys were removed and prepared for the histological and electron microscopical examinations. On histological examination, group A kidneys showed severe glomerular hyalinization (more than 80%) and frequent crescents, as well as tubulo-interstitial fibrosis and many protein casts. In contrast, segmental glomerular lesions were identified in group B kidneys. Tubulo-interstitium were also well preserved. Furthermore, the ultrastructural findings of group B were milder than that of group A. The preservation of renal tissue in group B revealed the beneficial effect of AST-120 on CRF rats' kidneys. In conclusion, this beneficial effect is provided by the removal of the serum toxic metabolite (uremic toxin) and the precursor substance of the toxin by orally administered AST-120.

This study investigated the release of prostacyclin (PGI 2 ) and thromboxane A 2 (TXA 2 ) from the aortic walls of various experimental hypertensive rats, e.g. spontaneously hypertensive rats (SHR), Dahl salt-sensitive (Dahl S) rats, deoxycorticosterone (DOCA)-salt hypertensive rats and renovascular (2-kidney, 1-clip (2K1C) and 1-kidney, 1-clip (1K1C) hypertensive rats. The PGI 2 generation was increased significantly in these hypertensive models, irrespective of the hypertensive mechanisms, when they developed established hypertension. Dahl S rats, having an impaired PGI 2 production on a low salt diet, restored PGI 2 generating capacity to the control level of Dahl salt-resistant rats when they were fed a high salt diet and developed salt-induced hypertension. On the other hand, the TXA 2 generation in the vascular walls was enhanced particularly in rat models for genetic hypertension, and this system was unaltered in the models for secondary hypertension, e.g. DOCA-salt and renovascular hypertension. Thus, it is suggested that the elevation of blood pressure is associated with an increase in vascular PGI 2 production, and that the increased vascular TXA 2 production is a characteristic feature of genetic hypertension.

Quantitative and qualitative evaluations of erythrocyte ferritin in 161 patients with RA and RAEB in MDS, AML, CML, PV, PA, HS, IDA, chronic liver disease and alcoholic liver disease were carried out. Mean erythrocyte ferritin levels of patients with RA, AML, PA, HS and alcoholic liver disease were increased compared with normal subjects. On isoelectric focusing analyses (IEF), erythrocyte ferritin in normal subjects were detected between pI 5.1 and 5.7. In the cases of RA, pI ranges of erythrocyte ferritin may be divided into three groups, acidic, neutral, basic shift on IEF respectively. In these groups, the more acidic the ferritin shift, the higher the proportion of morphological abnormalities of the erythroid precursors in the bone marrow was observed. In patients with AML (M2, M3, M4), little difference was found among these three subtypes, and all of the cases showed similar pattern with normal subjects on IEF. The ferritin from IDA showed low levels and slight basic shift compared with normal subjects on IEF, and these features were also found in patients with CML (chronic phase) and PV. After iron supplementation, marked increase of acidic ferritin was detected on IEF indicating an intermediate store for iron destined for haem synthesis. It was clear that the stainable iron in liver parenchymal cells were found at erythrocyte ferritin concentration 20 ag/cell or over in patients with chronic liver disease. Measurement of erythrocyte ferritin concentration is a helpful method for evaluating iron deposition in hepatocyte non-invasively. From these results it is considered that quantitative and qualitative analyses of erythrocyte ferritin are very useful for evaluating erythropoiesis as well as iron metabolism.

Feeding-related behavior and alteration of brain monoamine metabolism were examined in the male lean, and obese Zucker rats. Ambulatory activity of obese rats was reduced in the dark cycle. Dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC), contents were significantly decreased in the striatum of obese rats. However, the metabolic rate assessed with the DOPAC/DA ratio, and norepinephrine (EN) content were not changed in the striatum. Hypothalamic DA and NE contents were significantly reduced and the DOPAC/DA ratio was significantly increased in the hypothalamus of obese rats. The present findings suggest that the observed changes in brain monoamine metabolism may contribute to the development of obesity reducing ambulatory activity of obese rats.

The present studies were undertaken to examine the hypothesis that sucrose feeding at weaning may alter the preference for sucrose in the adolescence. Chronological changes of hypothalamic dopamine (DA), its metabolite, 3,4-dihydroxy-phenylacetic acid (DOPAC) and norepinephrine (NE) contents were also measured by HPLC. In 21 day-aged rats, 10% sucrose or water was given as drinking water for 3 weeks. From 9 weeks, all animals were maintained under a free choice between 30% sucrose solution and water. Sucrose-ingested rats more preferred to 30% sucrose solution than control rats and body weight gain of sucrose group was significantly greater than that of controls. Hypothalamic DA content was significantly decreased at 6 and 13 weeks and the DOPAC/DA ratio increased at 3, 6, and 13 weeks later. In contrast, hypothalamic NE concentration was not changed at all. The data obtained herein suggest that sucrose feeding at weaning alters the preference for sucrose, resulting in an overweight gain, and that the observed increase of hypothalamic DA metabolism may be involved in the altered preference for sucrose.

The architecture of the medial smooth muscle of arterial vessels in normal human brains was investigated using scanning electron microscopy. We could divide the arterial vessels into four subdivisions according to the number of the circular muscle cells. The arteries (greater than 100 microns in diameter) had 4-20 layers of circular smooth muscle cells; individual circular muscle cells were spindle-shaped and occasionally had branches at their ends. Multidirectional muscle cells were observed in the medio-adventitial border only at the branching sites in large arteries (greater than 300 microns), but at both branching and non-branching sites in the small arteries (100-300 microns). The nonterminal arterioles (30-100 microns) had 2-3 layers of circular muscle cells; most of the circular muscle cells had nodular or rod-like processes at their branched ends. Multidirectional muscle cells were most frequently observed in the medio-adventitial border in this subdivision at both branching and non-branching sites. The terminal arterioles (10-30 microns) had a single layer of circular muscle cells. Multipolar (stellate in appearance) smooth muscle cells were mainly seen in the medio-adventitial border at branching sites. The precapillary arterioles (7-10 microns) had a single layer of branched muscle cells; individual muscle cells had 2-4 circular branches on both sides of the central bulges.

An obese patient with nephrotic syndrome was admitted to the hospital because of increasing edema in the legs. With 25 kg weight loss, proteinuria decreased from 15 g to 5 g/day. Renal biopsy revealed mesangial glomerulopathy. The serum IgE level was highly elevated, and the radioallergosorbent test (RAST) was strongly positive for many kinds of allergens. No significant change in proteinuria, compared with the highly right atrial pressure period, was observed after normalization in the right atrial pressure. In spite of a decrease in body weight (27 kg) (113 to 86 kg) in 140 days, no significant change in proteinuria was observed. After additional therapy with an anti-allergic drug, proteinuria was completely abolished. These results suggest that a combination of weight loss and treatment with an anti-allergic drug is very important therapy for massive obesity with nephrotic syndrome. Since RAST was strongly positive for many kinds of allergens, the pathophysiology in this nephrotic syndrome may be, at least partially, related to the immunologic abnormalities.

Changes in myoepithelial cells (MECs) during perinatal development were examined by using the fluorescent probe for actin, nitrobenzoxadiazole (NBD)-phallacidin. By the twentieth day of gestation, there was no distinct fluorescent pattern suggestive of MECs. In newborn and 1-day-old rats, cells with diffuse fluorescence occurred around the acini, representing incipient MECs. Between 3 and 4 days after birth, actin staining was concentrated in strands which were arranged parallel to the long axis of the cell processes. MECs had developed further by the tenth day after birth with an increased number and thickness of their processes. Fully developed MECs were found between the thirtieth and fortieth day. These were stellate and encompassed individual acini.

A case of generalized juvenile gastrointestinal polyposis associated with gastric adenocarcinoma is described. A 31-year-old male patient developed polyposis of the stomach complicated by gastric carcinoma and multiple polyps in the colon. Polyps of the stomach and colon were pathologically consistent with juvenile polyp, but adenomatous changes were also present in a very small percentage of the juvenile polyps. This case strongly suggests the possibility of carcinoma developing in patients with generalized juvenile gastrointestinal polyposis.

In order to assess the roles of vasoconstrictor thromboxane in the antihypertensive action of alpha 1 adrenoceptor antagonist, we explored the influences of OKY-046, a selective thromboxane inhibitor, on the antihypertensive effects of bunazosin in spontaneously hypertensive rats (SHR). 2-week antihypertensive treatment with bunazosin (0.5 mg/kg/day) did not produce a significant decrease of systolic blood pressure in SHR, as compared to untreated controls. The blood pressure reduction was associated with a decrease of PGI2/TXA2 in vascular eicosanoids generation (p less than 0.02) and an increase of TXA2 excretion in urine (p less than 0.05). A combination treatment with OKY-046 almost completely abolished the enhanced TXA2 generation in the vascular wall and kidney, which was strikingly associated with a potentiation of the blood pressure reduction by bunazosin treatment (176 vs 186 mmHg, p less than 0.01). Bunazosin directly stimulated TXA2 biosynthesis in vascular smooth muscle cells in culture in a dose-dependent manner. Thus, these data clearly indicate that bunazosin, a quinazoline derivative, enhances vasoconstrictor TXA2 system in the vascular wall and kidney possibly through direct actions, which would attenuate the antihypertensive effects of alpha 1 adrenoceptor antagonism by bunazosin treatment.