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At least 1,045 records · Page 58Linked to original sources
PubMed1995

The inhibition of sodium, potassium-stimulated ATPase and corneal swelling: the role played by polyols.

BACKGROUND: Sodium, potassium-stimulated adenosine triphosphatase (Na,K-ATPase; E. C. 3.6.1.37) is considered to be the principal corneal enzyme responsible for deturgescence. Some metabolites are known to inhibit Na,K-ATPase, including glucose and galactose. In diabetes, some cells take up high levels of glucose and are converted to the polyhydroxy alcohol: sorbitol. In galactosemia, a similar uptake of galactose may cause the intracellular formation of the polyhydroxy alcohol: galactatol. This study tested the possibility that polyhydroxy alcohols (polyols), metabolized from carbohydrates, might decrease Na,K-ATPase activity. METHODS: Cultured corneal endothelial cells were separately exposed to 20 mM of the polyols: sorbitol, galactitol, and xylitol. Media containing 5 mM glucose served as the control. Plasma membrane vesicles, containing the Na,K-ATPase, were isolated and tested for the enzyme's activity. RESULTS: We found that the enzyme, after exposure to polyols, had only 15%-20% of its normal activity when assayed with the control. CONCLUSIONS: Since corneal endothelial cells can generate polyols in diabetes mellitus, this result may explain why corneas are able to swell in individuals with poorly controlled diabetes.

Animals↗
PubMed1995

Retinal vascular endothelial cell endocytosis increases in early diabetes.

BACKGROUND: Several physiological studies in recent years have convincingly demonstrated increased clearance of intravascular protein tracers by several different tissues, including the retina, during early diabetes and galactosemia in the rat. This change has been described as a consequence of increased permeation, although vascular leakage has not been demonstrated, and the fate of such tracers remains unelucidated. EXPERIMENTAL DESIGN: A pilot study in this laboratory showed no evidence of vascular leakage but suggested increased endocytosis of horseradish peroxidase (HRP) by retinal vascular endothelial cells (RVECs) in early diabetes. We therefore quantified RVEC endocytosis in normal, streptozotocin (STZ)-treated nondiabetic and STZ-diabetic rats using the design-based stereology method of "vertical sections." A duration of diabetes (6 weeks) was chosen to approximate the time period in which other workers have demonstrated increased protein permeation of the retina. RESULTS: After a 20-minute exposure to the tracer, HRP reaction product was observed in small vesicular and tubular endosomes and larger multivesicular bodies of the RVECs. Stereological analysis revealed a 6.5-fold increase in the volume of HRP-containing organelles in the RVECs of diabetic rats compared with STZ-treated nondiabetics or normal controls. None of the animals in this study showed HRP reaction product outside the retinal vascular endothelium. CONCLUSIONS: A highly significant increase in RVEC endocytosis occurs in early diabetes. Increased RVEC endocytosis may contribute to the observed clearance of intravascular protein tracers by the retina during early diabetes.

Animals↗
PubMed1995

Formula allergy and intolerance.

There are two major types of adverse reactions in infant formulas: (1) formula allergy/hypersensitivity, which is an immunologic response, and (2) formula intolerance, which is a nonimmunologic response. Formula intolerance can occur in infants with an underlying congenital or acquired enzyme deficiency (disaccharidase deficiency, galactosemia, hereditary fructose intolerance). The clinical presentation, diagnosis, and treatment of both reactions are reviewed in this article. The appropriateness of the use of a variety of infant formulas is discussed. Guidelines for the prevention of allergic disease are described as well.

Carbohydrate Metabolism, Inborn Errors↗
PubMed1994

[Liver cirrhosis in metabolic disorders].

The most early cirrhosis is observed in newborns with neonatal hemachromatosis. Early cirrhosis occurs in hereditary tyrosinemia type I, peroxisomal diseases and glycogen storage disease (type IV). In Wilson's disease, a case complicated with cirrhosis was reported in a 4-year-old patient. Slowly progressive cirrhosis is seen in patients with familial progressive intrahepatic cholestasis. Focal biliary cirrhosis is found in cystic fibrosis of the pancreas. Moreover, many other metabolic disorders, except for urea cycle disorders, are occasionally or rarely complicated with cirrhosis. Early diagnosis and proper management could prevent the development of cirrhosis in patients with galactosemia, hereditary fructose intolerance, etc. The occurrence of hepatoma must be monitored in these patients. Liver transplantation is indicated in a part of the patients with cirrhosis.

Carcinoma, Hepatocellular↗
PubMed1993

Dysmyelinating and demyelinating conditions in infancy.

The myelin membrane is essential for rapid conduction of nerve impulses through the central nervous system. Failure of myelination--dysmyelination--may arise through several mechanisms. The synthesis of a particular myelin protein can be defective, as occurs for proteolipid protein in Pelizaeus-Merzbacher disease and for myelin basic protein in the 18q- syndrome. Delay in myelination with a more generalized diminution in white matter is characteristic of many inherited metabolic diseases, including galactosemia, pyridoxine-dependent seizure disorder, glutaric aciduria type 1, and infantile Refsum disease. Demyelination or breakdown in myelin is characteristic of metachromatic leukodystrophy, Krabbe disease, mitochondrial disorders, adrenoleukodystrophy, Canavan disease, Alexander disease, and orthochromatic leukodystrophy. A fourth category is reserved for malformation syndromes. These include Cockayne, Fukuyama, Walker-Warburg, and Angelman syndromes. Demyelination also occurs in HIV-infected individuals with central nervous system findings and in multiple sclerosis. Much of the evidence for leukodystrophy in these disorders comes from neuroimaging. Some of these disorders are treatable.

AIDS Dementia Complex↗
PubMedDate not supplied

Reproductive effects of maternal metabolic disorders: implications for pediatrics and obstetrics.

The reproductive effects of metabolic disorders in women can be divided into four categories. The first of these is infertility. Galactosemia with its complication of ovarian failure is the disorder in this category. This complication may be prenatal in origin but whether this is so and its cause are unknown. The second category includes pregnancy effects of maternal metabolic disorders. The urea cycle disorder ornithine transcarbamylase (OTC) deficiency, maternal maple syrup urine disease and maternal homocystinuria are in this category. In the first two disorders, postpartum life-threatening illness due to metabolic crisis has occurred. Maternal homocystinuria is associated with a high risk for postpartum thromboembolic complications. The third category is the pregnancy effect of a fetal metabolic disorder. Pregnancies in which the fetus had long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) have been complicated by the life-threatening (HELLP) syndrome during the third trimester. Rapid recovery of the mothers followed delivery, on occasion by emergency cesarean section. The fourth category is the fetal effects (teratogenicity) from a maternal metabolic disorder. The best-known example of this is maternal phenylketonuria (PKU), which produces microcephaly, mental retardation, congenital heart disease and intrauterine growth retardation. Treatment with a low phenylalanine diet begun before conception or no later than the earliest weeks of the first trimester markedly reduces the risk to the fetus and can result in normal offspring. Other examples of teratogenicity may include maternal homocystinuria and maternal hypothyroidism.

Female↗
PubMed1996

Neonatal cholestasis syndrome: an appraisal at a tertiary center.

OBJECTIVE: To know the magnitude, etiology and clinical profile, the efficacy of various investigations and the outcome in patients with neonatal cholestasis syndrome (NCS). DESIGN: Prospective evaluation of 60 consecutive infants with NCS (mean age 3.9 +/- 1.9 months; 49 males) over a period of 3.5 years. SETTING: Tertiary level referral gastroenterology center in North India. METHODS: Liver function tests, urine examination, serum antibodies against Cytomegalovirus (CMV), Rubella and Toxoplasma; abdominal ultrasonography, hepatobiliary scintigraphy and liver biopsy were done. In appropriate setting, laparotomy and surgical corrections were done for biliary tract disorders. RESULTS: NCS constituted 19% of pediatric liver diseases. Considerable delay in presentation was observed [mean delay, extrahepatic biliary atresia (EHBA) = 4 +/- 2.0 months, neonatal hepatitis (NH) = 2.2 +/- 1.3 months]. Thirty three (55%) infants had EHBA, 14 (23%) NH (4 CMV, 2 galactosemia, 1 urinary tract infection and 7 idiopathic), 2 (3%) paucity of intralobular bile ducts and 11 (18%) were of indeterminate etiology. Liver biopsy was the most accurate (96.4%) investigation in discriminating between EHBA and NH. Of the 18 operated infants with EHBA (portoenterostomy-15 and hepatico-jejunostomy-3), 10 were alive (mean follow up = 22.8 +/- 8.6 months) of which 4 were completely asymptomatic. CONCLUSIONS: (i) NCS is an important cause of liver disease in Indian children. (ii) It requires prompt referral, quick investigative approach and targeted management. (iii) Liver biopsy is highly accurate in differentiating EHBA and NH. (iv) infants with EHBA and compensated status of liver should undergo corrective surgery irrespective of age at presentation.

Biliary Atresia↗
PubMed1997

Characteristics and clinical value of an intravenous echo-enhancement agent in evaluation of high-grade internal carotid stenosis.

Although ultrasound is a highly useful tool for clinical diagnosis, it has certain limitations in accurately quantifying internal carotid stenosis or diagnosing internal carotid occlusion. However, these limitations can be overcome by increasing the echogenicity of flowing arterial blood by use of echo-enhancement agents. Two phase III studies assessed the usefulness of the IV transpulmonary echo enhancer Levovist (SH U 508A) in improving characterization and quantification of severe internal carotid stenosis on ultrasound scans. In addition, Levovist-induced enhancement characteristics of the Doppler frequency spectrum have been analyzed. To be included in the study reviewed here, patients had to have a high-grade (> or = 70%) stenosis or occlusion of an internal carotid artery (ICA), as judged by conventional angiography or by standard cervical Doppler ultrasound. Patients were excluded from consideration if they were pregnant or nursing, had a history of galactosemia, or had received an ionic contrast medium within 24 hours before or after the intended administration of Levovist. Written informed consent was obtained from all patients before entry into the study. Of 32 patients (14 women, 18 men, median age 64 yr) who were included in this study, high-grade stenosis was verified in 30 ICA vessels and occlusion was verified in two vessels. After admission into the study, the carotid bifurcation was insonated in all patients using a 7.5-MHz linear array transducer for color Doppler-assisted duplex imaging and a 4-MHz pulsed-wave Doppler for velocity spectrum measurements before and after injection of the echo enhancement agent Levovist. Levovist-induced increases in carotid blood echogenicity began 11 +/- 2 seconds (mean +/- SD) after the start of injection, peaked at 21 +/- 2 dB, and had a half-life of 75 seconds. A fast Fourier transform of the original Doppler velocity spectrum demonstrated Levovist-induced enhancement throughout the entire velocity spectrum, with an increase in ICA blood flow velocity paralleling an increase in reflected ultrasound energy. Quantitative vascular measurements (cross-sectional luminal area reduction and plaque length) obtained before and during echo enhancement were highly correlated (r > 0.90). However, visualization of the entire length of the intrastenotic residual flow lumen, was significantly improved by Levovist enhancement (52% versus 83%; p = 0.01). Levovist considerably increased interpretable data by improving image quality in patients with high-grade carotid stenosis. Furthermore, the significant improvement in visualization of the residual flow lumen suggests that echo-enhancement agents may be most useful in improving the ultrasonography-based diagnosis of internal carotid occlusion.

Blood Flow Velocity↗
PubMed1997

Efficacy of treatment after measurable diabeticlike retinopathy in galactose-fed rats.

PURPOSE: To determine whether the diabeticlike retinal microangiopathies of the galactose-fed rat model could be ameliorated if intervention by withdrawal of the galactose diet or treatment with the aldose reductase inhibitor AL-3152 was initiated after quantifiable microangiopathies had occurred. METHODS: Weanling male Sprague-Dawley rats were randomized into five groups and fed for up to 24 months Purina laboratory chow (#5001) plus 50% starch (control [CON]), 50% D-galactose (galactose [GAL]), 50% D-galactose with AL-3152 (approximately 14 mg/kg per day) (prevention [PRV]), 50% D-galactose for 6 months followed by intervention with the inhibitor (intervention [INT]), or 50% D-galactose for 6 months followed by replacement with the 50% starch diet (withdrawal [GWD]). In rats on experimental diets and killed after 6, 18, and 24 months, one retina was prepared for transmission electron microscopy; the other was used for vessel wholemounts using elastase digestion. Capillary images were analyzed by computer morphometry. RESULTS: At 6 months, the GAL rats exhibited statistically significant (P < 0.05) increases over CON rats in mean capillary basement membrane thickness, capillary density, and dilated channels. These parameters tended to increase with time in most groups, and the differences between GAL and age-matched CON rats were maintained at the 18- and 24-month endpoints. Although the microangiopathies were ameliorated by AL-3152 treatment from the onset (PRV), intervention after 6 months of galactosemia with either galactose withdrawal (GWD) or addition of inhibitor (INT) showed amelioration in only some parameters at 18 months and no statistically significant benefit at the 24-month endpoint. CONCLUSIONS: Amelioration of galactose-induced retinal microangiopathies with AL-3152 in the prevention group suggests an efficacious application of aldose reductase inhibitors in treating diabetic retinopathy, provided treatment can begin soon after the onset of diabetes. Intervention after some of the earliest microscopic lesions neither halted progression of the angiopathy nor provided appreciable benefit at the 24-month follow-up.

Aldehyde Reductase↗
PubMed1998

[Neonatal screening for congenital metabolic disorders in Bavaria--assessment of current status and planned reorganization].

Newborn screening for inborn errors of metabolism is one of the most important achievements of preventive medicine to avoid disabilities and childrens death. In Bavaria, like in the rest of germany, the guthrie test for phenylketonuria was established in the late sixties. In the early eighties the introduction of screening for galactosemia and hypothyreodism followed. Considering actual problems (mixed finances, poor quality assurance) and recent methodological advances (tandem mass spectrometry) the current system needs reforming. At present, efforts are made to realize a concept for the reorganization of newborn screening in Bavaria. A new center with distributed functions for the public health services (quality assurance), the university of Munich (science) and a private laboratory (analysis) is planned.

Cost Control↗
PubMedDate not supplied

Cystic fibrosis: molecular approaches to diagnosis.

Whole blood collected on filter paper (Guthrie cards) has provided an excellent means for screening inborn errors of metabolism in neonates. Traditional biochemical methods adapted for use with this collection device have proven instrumental in the detection of many congenital defects such as phenylketonuria, galactosemia, hypothyroidism and hemoglobinopathies. The advent of molecular techniques, specifically polymerase chain reaction (PCR), has resulted in unparalleled advances in diagnostic sensitivity. Because of its ability to amplify small quantities of deoxyribonucleic acid (DNA), PCR has proven particularly successful for use with Guthrie card bloodspots in the identification of many genetic disorders including cystic fibrosis, sickle cell anemia and muscular dystrophy. Furthermore, it has been suggested that Guthrie cards represent a vast archive of genomic material yet to be explored. In this article we review our experience using Guthrie card bloodspots for PCR amplification of the cystic fibrosis gene, describe the advantages and limitations of this technology and speculate on future prospects for molecular diagnostics over the next 100 years.

Blood Specimen Collection↗
PubMed1998

Inositol--clinical applications for exogenous use.

Recent advances in nutritional and biochemical research have documented inositol as an important dietary and cellular constituent. The processes involved in inositol metabolism and its derivatives in the tissues of mammals have been characterized in vivo as well as at the enzymatic level. Biochemical functions defined for phosphatidylinositol in biological membranes include the regulation of cellular responses to external stimuli and/or nerve transmission as well as the mediation of enzyme activity through interactions with various specific proteins. Altered production of inositol has been documented in patients with diabetes mellitus, chronic renal failure, galactosemia, and multiple sclerosis. Inositol has been reported to be effective in treating central nervous system disorders such as depression, Alzheimer's disease, panic disorder, and obsessive-compulsive disorder. It has documented benefit for use in pediatric respiratory depression syndrome. In addition, recent studies have evaluated its usefulness as an analgesic. Inositol has been studied extensively as potential treatment to alleviate some negative effects associated with lithium therapy. The use of inositol in pregnant women remains controversial. Although its benefit in preventing neural tube defects in embryonic mice is documented, the risk of inducing uterine contractions limits its usefulness in pregnancy.

Animals↗