Pathological excretion patterns of urinary proteins in renal cell cancer patients exposed to trichloroethylene

A study was carried out to investigate urinary protein excretion patterns by means of SDS-polyacrylamide-gel-electrophoresis (SDS-PAGE) in renal cell cancer patients who had previously been exposed to high levels of trichloroethylene. Thirty-eight out of 41 (93%) renal cell cancer patients investigated had former extensive trichloroethylene exposure, but only 23 out of 50 (46%) renal cell cancer patients without a history of occupational exposure to trichloroethylene revealed urinary protein patterns indicative of toxic effects on the tubular system. One hundred controls without histories of overt renal disease and not occupationally exposed to trichloroethylene were examined in the same way; only 11 (11%) of them displayed protein excretion patterns indicative of damage to the renal tubule. These results are supported by alpha 1-microglobulin excretion data. The following conclusions are drawn: (1) Substantially more cases of tubular damage are found amongst renal cell carcinoma patients having been exposed to substantial levels of trichloroethylene over many years as compared with renal cell carcinoma patients not exposed to trichloroethylene. (2) The results support the view that chronic tubular damage is a precondition for the nephrocarcinogenic effect of trichloroethylene. (3) The findings indicate that urine protein patterns, on the basis of the SDS-PAGE methodology, represent a 'biological effect parameter' for the medical surveillance of persons occupationally exposed to trichloroethylene.     

Thirteen-week inhalation toxicity of p-dichlorobenzene in mice and rats

Subchronic inhalation toxicity of p-dichlorobenzene (p-DCB) was examined by exposing BDF1 mice and F344 rats of both sexes (6 h/d and 5 d/wk) to inhalation of 25, 55, 120, 270 or 600 ppm (v/v) p-DCB vapor for 13 wk. The exposure to p-DCB vapor retarded the growth rate in the male mice, and induced hepatotoxicity in the mice and rats of both sexes and renal and hematological toxicity in the male rats. Hepatotoxicity was characterized by increased liver weight, hepatocellular hypertrophy, and increased serum levels of total cholesterol. Liver necrosis and increased serum levels of AST and ALT were observed in the exposed mice, whereas these changes, which indicate hepatocellular death, did not occur in any of the exposed rats. p-DCB-induced renal lesions occurred only in the male rats. Hyaline droplets were observed in the proximal tubular epithelial cells, and were stained positively with anti-alpha2u-globulin, suggesting excessive accumulation of alpha2u-globulin in the epithelial cells. Granular casts were formed in the tubular lumen, resulting from the necrotic desquamation of the renal tubular epithelium. Papillary mineralization in the renal pelvis and increased serum levels of BUN and creatinine were noted. These renal changes indicated alpha2u-globulin nephropathy. Decreases in red blood cell counts, hemoglobin concentration, hematocrit and mean corpuscular volume and increased spleen weight occurred in the exposed male rats. The NOAEL was 120 ppm for the hepatic endpoint in mice and for the renal endpoint in rats. The maximum tolerated dose for a 2-yr bioassay inhalation study of rodent carcinogenicity was estimated to be 300 ppm, based on the present results.     

Selective damage of pulmonary nonciliated bronchiolar epithelial (Clara) cells by trichloroethylene in rats

Ethanol-treated and ethanol-nontreated rats were exposed to 0, 500, 1,000, 2,000, 4,000 and 8,000 ppm of trichloroethylene for 2 h in order to evaluate the metabolic (metabolic rate of styrene) and morphologic changes in the lung. The exposure resulted in dose-dependent decrease of styrene metabolism. By MPA (Maclura pomifera agglutinin) stain it was revealed by light microscopy that trichloroethylene caused a highly selective damage to nonciliated bronchiolar epithelial (Clara) cells, which were characterized by flattened cells. The ratios of the length of apical surface (a) to the length of the base (b) of Clara cells analyzed morphometrically decreased dependent on trichloroethylene dose. Electron microscopy showed that the bronchiolar luminal surface was covered by flattened and dilated endoplasmic reticulum and that destruction of mitochondrial crista and disappearance of secretory granules were dependent on increase in trichloroethylene concentration. Time-course studies conducted with exposure of 8,000 ppm of trichloroethylene to ethanol-treated rats demonstrated that maximal Clara cell damage occurred between 8 and 22 h after exposure, and that the cells appeared to be virtually identical to these of the control by 4 wk after exposure. Ethanol ingestion slightly increased Clara cell damage induced by trichloroethylene.     

Dietary guar gum halts further renal enlargement in rats with established diabetes.

Guar gum, a dietary fiber known to improve glucose tolerance, was fed to rats with established diabetes to determine its effect on renal enlargement and microalbuminuria. Diabetic rats were fed a modified AIN-76A (basal) diet for 4 wk, at which time half the rats continued to receive the same basal diet (DB-BA group) and half were switched to a 5% guar gum diet (DB-GG group). Nondiabetic rats fed the basal diet served as controls (NRL group). After 8 additional weeks the animals were killed. Glycated hemoglobin, a measure of long-term blood glucose control, was 14.4% in the DB-BA group and 12.4% in the DB-GG group, a statistically significant difference (P < 0.05). Kidney weight of the DB-BA group (3.51 g) was significantly greater than that of the DB-GG group (2.76 g) (P < 0.05). Eight weeks after induction of diabetes, 24-h urinary albumin excretion was highest in the DB-BA group and lowest in the NRL group; excretion in the DB-GG group (4 wk of guar feeding) was intermediate. However, by 12 wk no differences in albumin excretion among the groups were apparent. These results suggest that guar gum may be useful for slowing the progression of diabetic nephropathy and that guar gum deserves further study in this regard.     

Gluconeogenic substrates and hepatic gluconeogenic enzymes in streptozotocin-diabetic rats: effect of mulberry (Morus indica L.) leaves

Mulberry (Morus indica L.) leaves, the sole food of the silk worm, were evaluated for antidiabetic effects in streptozotocin (STZ)-diabetic rats. Treatment with dried mulberry leaf powder at 25% of the diet for a period of 8 weeks was found to be remarkably beneficial to STZ-diabetic rats as evidenced by controlled hyperglycemia and glycosuria. In addition, mulberry leaves countered (reversed) the alterations in gluconeogenic substrates in STZ-diabetic rats as indicated by significant reduction in serum pyruvic and lactic acid levels, a significant increase in proteins and a significant decrease in free amino acid, urea, and creatinine levels in blood, and a decreased urinary excretion of urea and creatinine. Anomalies in the activities of hepatic gluconeogenic enzymes associated with impaired glucose homeostasis in STZ-diabetic rats were ameliorated by feeding the mulberry leaf-supplemented diet, indicating that control over hyperglycemia and associated complications in the diabetic state by mulberry leaves is by way of regulation of gluconeogenesis. With respect to all the parameters, mulberry leaves were more effective than the oral hypoglycemic drug glibenclamide.     

Relations between liver cadmium, cumulative exposure, and renal function in cadmium alloy workers.

Detailed biochemical investigations of renal function were made on 75 male workers exposed to cadmium and an equal number of referents matched for age, sex, and employment status. The exposed group consisted of current and retired workers who had been employed in the manufacture of copper-cadmium alloy at a single factory in the United Kingdom for periods of up to 39 years and for whom cumulative cadmium exposure indices could be calculated. In vivo measurements of liver and kidney cadmium burden were made on exposed and referent workers using a transportable neutron activation analysis facility. Significant increases in the urinary excretion of albumin, retinol binding protein, beta 2 microglobulin, N-acetylglucosaminidase (NAG), alkaline phosphatase, gamma-glutamyl transferase and significant decreases in the renal reabsorption of calcium, urate, and phosphate were found in the exposed group compared with the referent group. Measures of glomerular filtration rate (GFR) (creatinine clearance, serum creatinine, and beta 2 microglobulin) indicated a reduction in GFR in the exposed population. Many of these tubular and glomerular function indicators were significantly correlated with both cumulative exposure index and liver cadmium burden. Using cumulative exposure index and liver cadmium as estimates of dose, a two phase linear regression model was applied to identify an inflection point signifying a threshold level above which changes in renal function occur. Many biochemical variables fitted this model; urinary total protein, retinol binding protein, albumin, and beta 2 microglobulin gave similar inflection points at cumulative exposure levels of about 1100 y.micrograms/m3 whereas changes in the tubular reabsorption of urate and phosphate occurred at higher cumulative exposure indices. Measures of GFR, although fitting the threshold model did not give well defined inflection points. Fewer variables fitted the two phase model using liver cadmium; those that did gave threshold levels in the range 20.3-55.1 ppm. When cadmium workers with cumulative exposure indices of less than 1100 y.micrograms/m3 were compared with their respective referents only serum beta 2 microglobulin and urinary NAG were significantly increased in the exposed group and these differences were not related to the degree of cadmium exposure.(ABSTRACT TRUNCATED AT 400 WORDS)     

Neurotoxicity of allyl chloride in rats. Dose-effect relationship following long-term exposure

To elucidate the dose-effect relationship of neurotoxicity of allyl chloride (AC) in Donryu rats, 5 animals each were exposed to 10, 50 and 100 ppm AC for 8 h/d and 5 d/wk for a period of 34 wk. Nerve conduction velocities of the tail nerve in rats were determined before and after 4, 8, 12, 16, 22, 28 and 34 wk of exposure, and the width of landing foot-spread after 8, 12, 16, 28 and 34 wk. Animals subjected to 100 ppm AC showed significant (p less than 0.01) reduction of motor and sensory nerve conduction velocities and nerve action potentials (NAP) after 28 wk when clinical signs of neuropathy were observed, i.e., weakness of hindlimbs and significantly (p less than 0.01) extended landing foot-spreads. Motor distal latency was retarded in rats exposed to 100 ppm AC at the last period of exposure. In rats exposed to 50 and 100 ppm AC, no remarkable electrophysiological findings or abnormal clinical signs were observed except for depressed amplitude of NAP in 50 ppm-exposed rats when compared with those exposed to 10 ppm.     

Characterization of trihalomethane (THM)-induced renal dysfunction in the rat. II: Relative potency of THMs in promoting renal dysfunction

Single non-lethal doses (3 mmol/kg) of chloroform (CHCl₃), dichlorobromomethane (CHCl₂Br), dibromochloromethane (CHClBr₂), and bromoform (CHBr₃) were administered by intraperitoneal injection to male Sprague-Dawley rats and proximal tubular secretion and reabsorption was assessed at varied times following treatment. Each of the trihalomethanes (THMs) at this dose inhibited proximal tubular secretion, as indicated by decreased in vitro renal cortical slice accumulation of organic anion p-aminohippuric acid (¹⁴C PAH). The time of maximal THM interference with ¹⁴C PAH uptake occurred at 8 h, with recovery being demonstrated by 48 h. Each of the THMs also demonstrated interference with tubular reabsorption, as assessed by urinary glucose excretion, with maximal interference occurring during the first day post-treatment and recovery being observed during the second day post-treatment. In each case, CHCl₂Br was the most potent inhibitor of proximal tubular function. Combining these data with those of the preceding paper, the relative potency in disrupting renal function was, in general, CHCl₂Br>CHCl₃>CHClBr₂>CHBr₃. Since the time course of this investigation indicates that proximal tubular dysfunction precedes other THM-induced renal function interferences, it also appears that proximal tubular damage is the primary event leading to further manifestations of renal dysfunction.     

Urinary α<Subscript>1</Subscript>-microglobulin excretion as biomarker of renal toxicity in trichloroethylene-exposed persons

Objectives Concern on human renal toxicity and carcinogenicity of trichloroethylene is based on findings of increased incidences of renal cell cancers in persons with long-lasting and high occupational exposures to this solvent. The full tumour development is likely to require promotional stimuli, by repetitive episodes of high peak exposures to trichloroethylene, leading to nephrotoxicity. This process is visualised by the excretion of tubular marker proteins in the urine of exposed persons. For this purpose, surveillance of ₁-microglobulin excretion is being suggested by the Deutsche Forschungsgemeinschaft.Methods The present study assessed the applicability of ₁-microglobulin as a biomarker of proximal tubule damage in the prevention of nephrotoxicity by trichloroethylene exposures. For this purpose, ₁-microglobulin excretions were assessed in trichloroethylene-exposed and non-exposed subgroups of both cases (diseased with renal cancer) and controls (not diseased with renal cancer) of a recent case–control study.Results The median of ₁-microglobulin excretions in non-exposed persons was below the detection limit, but it was clearly elevated in exposed persons. The Wilcoxon rank sum test showed a significant difference (P=0.0090). Consistent with the underlying concept, renal cell cancer cases who had been exposed to trichloroethylene had higher ₁-microglobulin excretions than non-exposed cases (P=0.0005) and also had higher ₁-microglobulin excretions than exposed controls (P=0.0004). Of 20 trichloroethylene-exposed renal cell cancer cases only three (15%) displayed a normal ₁-microglobulin excretion of <5 mg/l. By contrast, 41 (52%) out of 79 non-exposed renal cancer cases showed normal excretions of the biomarker.Conclusion The present data are in agreement with the concept of pathogenesis of renal cell cancers developing under high (suggested: >500 ppm peak exposures) and long-term (several years) exposure to trichloroethylene. They also visualise the potential value of ₁-microglobulin excretion as a routine biomarker of renal toxicity that may be used in the medical surveillance of trichloroethylene-exposed persons.     

Calcium supplements and milk: effects on acid-base balance and on retention of calcium, magnesium, and phosphorus

The effect of supplementing a basal diet containing 697 mg calcium daily (17.4 mmol/d) with an additional 900 mg Ca daily from milk, Ca chloride, or a Ca carbonate preparation was examined in eight adult males during a 56-d metabolic balance study. The ingestion of the milk or Ca supplements had no overall effect on Ca retention by these subjects because the milk and supplements depressed apparent absorption of Ca in the gut and fractional tubular reabsorption of Ca in the kidneys. Supplementation of the diet with CaCl and to a lesser extent with milk significantly increased renal acid excretion whereas supplementation with CaCO3 depressed renal acid excretion. The three Ca supplements significantly altered magnesium and phosphorus absorption and urinary excretion in different manners but had no overall effect on retention of P or Mg. The responses of our subjects to these treatments may be different than those of subjects who are chronically in negative balance in regard to Ca.     

Long-term sucrose and glucose consumption decreases the delta-aminolevulinate dehydratase activity in mice

OBJECTIVE: This study evaluated the long-term effects of high-glucose (GLU) and high-sucrose (SUC) diets on the development of obesity, abdominal fat deposition, glucose intolerance, oxidative stress and effects on delta-aminolevulinate dehydratase (delta-ALA-D) activity in various organs. In particular, the effect of aging on these parameters was evaluated. METHODS: Mice were assigned to a baseline, control, or experimental group. The control group was provided with tap water and experimental groups with solutions of glucose or sucrose for 30 wk. To verify the effect of aging, young mice (baseline group, 8 wk old) were compared with aged animals (control and experimental groups, 38 wk old). RESULTS: Consumption of GLU or SUC diets caused increases in body weight, abdominal fat index, and fasting plasma glucose levels. A positive correlation was observed between the abdominal fat index and fasting glucose levels. There was a significant increase in levels of thiobarbituric acid-reactive species (TBARS) and a significant decrease in delta-ALA-D activity in various tissues of GLU and SUC feeding mice. Importantly, the dithiothreitol-induced enzymatic reactivation in the GLU and SUC groups was significantly higher than in the control group, and in the aged group it was significantly higher than in the baseline group. After 30 wk, the experimental groups had a decrease in delta-ALA-D activity and an increase in TBARS levels in relation to the baseline group. CONCLUSION: Alterations in the activity of the delta-ALA-D found in this work demonstrate the possible contributions of hyperglycemia and aging for protein oxidation, leading to impairment of its biologic function.     

术前糖负荷促进胰岛素早相分泌维持围手术期血糖平稳

目的:在围手术期营养支持严格热量控制的情况下,观察病人围手术期血糖的变化,并探讨术前糖负荷对围手术期血糖的影响。方法:选择60例择期行结直肠手术的病人,随机分为两组。试验组病人术前给予糖负荷,而对照组则按传统的围手术期方案不给予糖负荷,观察两组病人围手术期的胰岛素分泌状况和血糖变化情况。结果:手术病人于术后血糖均明显升高,至术后第6天仍处于应激性高血糖状态。两组病人手术当天血糖变化曲线存在明显差异,对照组在手术期间无明显胰岛素分泌,并出现明显的应激性高血糖,而试验组在手术期间出现明显的胰岛素分泌,并且血糖保持更为平稳。结论:手术可导致病人出现应激性高血糖,术前给予糖负荷可促进胰岛素早相分泌,有利于围手术期病人的血糖控制。     

Radioactive Fallout

Rats with implanted hypothalamic electrodes were trained to press a lever for electrical brain stimulation during a daily 30 minute test period. In rats continuously deprived of water for three days, the rate of lever-pressing declined slightly on the first day but remained at that level during the next two days. Exposure of nondehydrated rats to high concentrations of trichloroethylene during the text periods markedly depressed the rate of pressing on three consecutive days. In rats deprived of water for three days and exposed to trichloroethylene daily, the onset of depression was delayed during each test period, and greater tolerance to trichloroethylene developed than in nondehydrated rats. When these rats were later deprived of water for ten days, the rate decreased progressively from days 5 to 10, which was not characteristic of control rats.     

Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes

BACKGROUND: Taurine, a potent antioxidant, has been reported to improve streptozotocin-induced diabetes mellitus, in which the development of diabetes results from an attack by oxygen free radicals on pancreatic beta cells. However, taurine also increases the excretion of cholesterol via conversion to bile acid and would be expected to improve insulin resistance. OBJECTIVE: The effects of taurine on insulin sensitivity were examined in a model rat of insulin resistance and type 2 diabetes-the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. DESIGN: Male OLETF rats were divided into 2 groups at the age of 16 wk: a taurine-supplemented group and an unsupplemented group. As a nondiabetic control, Long-Evans-Tokushima-Otsuka rats were used. An oral-glucose-tolerance test and hyperinsulinemic euglycemic clamp were performed at the ages of 23 and 25 wk. RESULTS: The OLETF rats had hyperglycemia and insulin resistance and they had a greater accumulation of abdominal fat than did control rats. Abdominal fat accumulation, hyperglycemia, and insulin resistance were significantly lower in the taurine-supplemented group than in the unsupplemented group. Serum and liver concentrations of triacylglycerol and cholesterol were significantly higher in the OLETF rats than in the control rats and were significantly lower in the taurine-supplemented group than in the unsupplemented group, presumably because of the increased secretion of cholesterol into bile acid. Taurine-supplemented rats also showed higher nitric oxide secretion, evidenced by increased urinary excretion of nitrite. CONCLUSION: Taurine effectively improves metabolism in OLETF rats by decreasing serum cholesterol and triacylglycerol, presumably via increased secretion of cholesterol into bile acid and decreased production of cholesterol because of increased nitric oxide production.     

系统化健康教育对肾移植术后患者血糖的影响研究

目的探讨系统化健康教育对肾移植术后患者血糖水平的影响。方法采用随机分组，将204例肾移植术后患者随机分为观察组（102例）和埘照组（102例），对照组采用传统的随机式健康教育，观察组采用系统化健康教育；6个月后比较两组患者饮食、运动、掌握疾病相关知识、患者满意度，分析患者宅腹及餐后2h血糖控制水平。结果观察组饮食、运动、掌握疾病相关知识、患者满意度及血糖控制水平均优于对照组，两组比较差异有统计学意义（P〈0．05）。结论系统化健康教育有利于控制患者血糖水平，预防和延缓PTDM的发生，提高患者对护理工作的满意度。     

Relations between liver cadmium, cumulative exposure, and renal function in cadmium alloy workers

Detailed biochemical investigations of renal function were made on 75 male workers exposed to cadmium and an equal number of referents matched for age, sex, and employment status. The exposed group consisted of current and retired workers who had been employed in the manufacture of copper-cadmium alloy at a single factory in the United Kingdom for periods of up to 39 years and for whom cumulative cadmium exposure indices could be calculated. In vivo measurements of liver and kidney cadmium burden were made on exposed and referent workers using a transportable neutron activation analysis facility. Significant increases in the urinary excretion of albumin, retinol binding protein, beta 2 microglobulin, N-acetylglucosaminidase (NAG), alkaline phosphatase, gamma-glutamyl transferase and significant decreases in the renal reabsorption of calcium, urate, and phosphate were found in the exposed group compared with the referent group. Measures of glomerular filtration rate (GFR) (creatinine clearance, serum creatinine, and beta 2 microglobulin) indicated a reduction in GFR in the exposed population. Many of these tubular and glomerular function indicators were significantly correlated with both cumulative exposure index and liver cadmium burden. Using cumulative exposure index and liver cadmium as estimates of dose, a two phase linear regression model was applied to identify an inflection point signifying a threshold level above which changes in renal function occur. Many biochemical variables fitted this model; urinary total protein, retinol binding protein, albumin, and beta 2 microglobulin gave similar inflection points at cumulative exposure levels of about 1100 y.micrograms/m3 whereas changes in the tubular reabsorption of urate and phosphate occurred at higher cumulative exposure indices. Measures of GFR, although fitting the threshold model did not give well defined inflection points. Fewer variables fitted the two phase model using liver cadmium; those that did gave threshold levels in the range 20.3-55.1 ppm. When cadmium workers with cumulative exposure indices of less than 1100 y.micrograms/m3 were compared with their respective referents only serum beta 2 microglobulin and urinary NAG were significantly increased in the exposed group and these differences were not related to the degree of cadmium exposure.(ABSTRACT TRUNCATED AT 400 WORDS)     

Assessment of renal function in workers previously exposed to cadmium

Cadmium induced renal effects were examined in 60 workers (58 men, 2 women) previously exposed to cadmium. Tubular damage in the form of beta 2-microglobulinuria was found in 40%, and urinary albumin and orosomucoid increased significantly with increasing urinary cadmium and increasing relative clearance of beta 2-microglobulin. It is suggested that increased albumin excretion is secondary to the tubular damage. In no case was typical glomerular proteinuria found that could be related to cadmium. Histories of renal stones were more common among the workers with high urinary cadmium concentrations. The glomerular filtration rate was measured in 17 of the workers who had pronounced tubular dysfunction. The average glomerular filtration rate for these men was less than the age adjusted predicted value (mean = 84%). Furthermore, there was a significant (p less than 0.05) correlation (r = -0.47) between tubular reabsorption loss and a decreased glomerular filtration rate.     

Occupational exposure to toluene and its possible causative role in renal damage development in shoe workers

Objectives: An important, although, unprecise number of shoe workers in Leon, Mexico, are in continuous contact with toluene-based glues. The induction of renal glomerular and/or tubular lesions as a result of toluene exposure is still being discussed controversially. Our objective was to evaluate the extent of occupational exposure, assessing urinary o-Cresol excretion as a measure for toluene exposure in a population at risk as compared to a control population. Urinary albumin excretion (UAE) and N-acetyl-β-D-glucosaminidase (NAG) enzymatic activity were tested to assess renal dysfunction. Methods: A cross-sectional study was performed comparing 50 toluene-exposed shoe workers and 25 control subjects. Urinary o-cresol was assessed on first and last day of labor week from exposed subjects. A single urine sample was obtained from control subjects. Urinary Albumin excretion (UAE) and (NAG) activity were examined in 12 h urine samples in all subjects. Urine and serum creatinine were measured to asses renal function. Results: At the end of the labor week, urinary o-cresol levels were higher in samples obtained from exposed subjects. Albumin excretion was similar in the exposed and control groups. NAG activity was greater in the exposed group compared to control group (median 3.5 U/g creatinine vs 1.9 U/g creatinine, z=2.6, P=0.009). An inverse relationship was found between schooling years and the NAG enzymatic activity for the two studied groups (r= −0.27, P=0.02), Conclusions: Our findings support the hypothesis that toluene may be a factor associated with the presence of renal damage in exposed shoe workers. As NAG activity is increased, we believe the lesion initiates in the renal tubular cells.     

Progressive adaptation of the endocrine pancreas during long-term protein deficiency in rats: effects on blood glucose homeostasis and on pancreatic insulin, glucagon and somatostatin concentrations

Blood glucose, plasma insulin and glucagon, as well as pancreatic insulin, glucagon and somatostatin contents, were measured in control (C group, 18% casein), deprived (D group, 5% casein) and pair-fed (PF) rats at seven intervals during 23 wk after weaning (wk 0). In C rats, plasma and pancreatic insulin showed parallel variations, in D rats, plasma insulin increased normally until wk 3 after weaning, dropped from wk 3 to 8 and was higher in wk 16 and 23 than in wk 8, while pancreatic insulin increased linearly after a significant drop between wk 0 and 1. Insulin variations in D rats were related to protein deficiency until wk 5, but only to energy deficiency thereafter. Circulating and pancreatic glucagon dropped identically for the three groups until wk 5: its role in adaptation to malnutrition is quite irrelevant, although a dysregulation of its secretion was noted. Protein-energy malnutrition induced an increase of pancreatic somatostatin content that was due to the energy deficiency. On the basis of the insulin-to-glucagon ratio, three phases of adaptation to protein-energy malnutrition appeared. From wk 0 to 3, the metabolic priority was growth, whereas glucose homeostasis was secondary, accounting for the early hypoglycemia. From wk 3 to 8 survival was the main priority. After wk 8, the various biochemical parameters stabilized, and growth was parallel to that of normal animals. Protein-energy malnutrition was responsible for a dissociated adaptation of pancreatic hormones.     

Acute alcohol intoxication in a two-month-old baby

A 2-month-old, well developed, healthy boy, weighing 5.55 kg, was fed 200 ml of bottle-milk containing 65 ml of sake. So-called kanzamashi (sake boiled in the evening and remaining in a bottle overnight,) was mistaken for yuzamashi (water boiled and left to cool), and used to prepare a 15% formula milk. About 10 minutes later, the baby became flushed, began to breath hard, and lose consciousness, and an alcoholic odor was noticed. He was brought to our clinic, where gastric lavage and parenteral fluid therapy were started. On admission, his main physical signs were, whole body had become red, unconsciousness, alcoholic odor, tachycardia and tachypnea, without low body temperature, while his remarked laboratory findings were metabolic acidosis, hyperglycemia, and high A/G ratio. Moreover, a transient proteinuria, alternately followed by a transient glycosuria, appeared within the course. About 10 hours later, he showed an obvious improvement in both physical and laboratory findings. As an explanation of these changes in his condition due to alcohol ingestion, we speculated that a metabolic acidosis with hyperglycemia caused the disturbed reabsorption in his renal tubulus, which revealed alternating proteinuria and glycosuria.