Calculated parameters for the diagnosis of Wilson disease

INTRODUCTION@#The diagnosis of Wilson disease (WD) is plagued by biochemical and clinical uncertainties. Thus, calculated parameters have been proposed. This study aimed to: (a) compare the diagnostic values of non-caeruloplasmin copper (NCC), NCC percentage (NCC%), copper-caeruloplasmin ratio (CCR) and adjusted copper in WD; and (b) derive and evaluate a discriminant function in diagnosing WD.@*METHODS@#A total of 213 subjects across all ages who were investigated for WD were recruited. WD was confirmed in 55 patients, and the rest were WD free. Based on serum copper and caeruloplasmin values, NCC, NCC%, CCR and adjusted copper were calculated for each subject. A function was derived using discriminant analysis, and the cut-off value was determined through receiver operating characteristic analysis. Classification accuracy was found by cross-tabulation.@*RESULTS@#Caeruloplasmin, total copper, NCC, NCC%, CCR, adjusted copper and discriminant function were significantly lower in WD compared to non-WD. Discriminant function showed the best diagnostic specificity (99.4%), sensitivity (98.2%) and classification accuracy (99.1%). Caeruloplasmin levels <0.14 g/L showed higher accuracy than the recommended 0.20 g/L cut-off value (97.7% vs. 87.8%). Similarly, molar NCC below the European cut-off of 1.6 umol/L showed higher accuracy than the American cut-off of 3.9 umol/L (80.3% vs. 59.6%) (P < 0.001). NCC%, mass NCC, CCR and adjusted copper showed poorer performances.@*CONCLUSION@#Discriminant function differentiates WD from non-WD with excellent specificity, sensitivity and accuracy. Performance of serum caeruloplasmin <0.14 g/L was better than that of <0.20 g/L. NCC, NCC%, CCR and adjusted copper are not helpful in diagnosing WD.

Clinical characteristics of Wilson's disease with onset of acute liver failure in 19 children / 中华儿科杂志

Objective: To analyze the clinical characteristics of Wilson's disease (WD) with onset of acute liver failure (ALF) in children. Methods: Clinical data of 19 children diagnosed with WD presented with ALF in Xi'an Children's Hospital from January 2016 to April 2021 were retrospectively analyzed, including general condition, clinical manifestation, laboratory examination, and gene detection. The children were divided into the death group and survival group according to the clinical outcome. The children who had hepatic WD with non-ALF onset during the same period were selected as the control. The general conditions and laboratory indexes were compared between death group and survival group, ALF group and non-ALF group. T-test, Mann Whitney U test or χ2 test were used to compare the differences between the two groups. Results: Of the 19 WD children with ALF onset, 10 were females and 9 were males. The age of admission was (10.1±2.6) years and time to onset of first visit was 9 (4, 15) days. Among the WD children with ALF onset, 4 children were lost to follow-up, 5 cases death (death group) and 10 cases survived (survival group). The ceruloplasmin in the death group was higher than that in the survival group (0.078 (0.055, 0.105) vs. 0.033 (0.027, 0.058) g/L, Z=-2.33, P=0.020). There were 95 children who had hepatic WD with non-ALF onset. The WD patients with ALF onset were older at admission (9.9 (8.0, 11.1) vs. 5.4 (3.7, 6.9) years, Z=-5.25, P<0.001), had higher ceruloplasmin (0.060 (0.030, 0.078) vs. 0.024 (0.006, 0.060) g/L, Z=-3.11, P=0.002), 24 h urinary copper (674 (205, 1 803) vs. 149 (108, 206) μg, Z=-4.25, P<0.001), and positive rate of K-F ring [17/19 vs. 7%(7/95), χ2=50.17, P<0.001] while shorter onset time at initial visit (0.3 (0.1, 0.5) vs. 1.0 (0.7, 6.0) months, Z=-4.28, P<0.001). There was no gender difference between the two groups [9/19 vs. 61%(58/95), χ2=1.22, P=0.269]. Of the 19 WD children with ALF onset, 13 had the ATP7B gene tested, and 15 reported variants were detected. The main variations were c.2333G>T (p. Arg778Leu), c.2621C>T (p. Ala874Val) and c.2975C>T (p. Pro992Leu). The allele frequencies were 6/26(23%), 4/26(15%) and 3/26(12%), respectively. Conclusions: Children of WD onset with ALF are school-aged and above. They have an acute onset, a short course of the disease, and poor prognosis. The positive rate of K-F ring, ceruloplasmin and urinary copper are higher than those of the hepatic WD children with non-ALF onset.

Phenotypes and ATP7B gene variants in 316 children with Wilson disease / 中华儿科杂志

Objectives: To summarize the clinical phenotypes and the variation spectrum of ATP7B gene in Chinese children with Wilson's disease (WD) and to investigate their significance for early diagnosis. Methods: Retrospective analysis was performed on the clinical data of 316 children diagnosed as WD in Guangzhou Women and Children's Medical Center during the period from January 2010 to June 2021. The general situations, clinical manifestations, lab test results, imaging examinations, and ATP7B gene variant characteristics were collected. The patients were divided into asymptomatic WD group and symptomatic WD group based on the presence or absence of clinical symptoms at the time that WD diagnosis was made. The χ2 test, t test or Mann-Whitney U test were used to compare the differences between groups. Results: Among the 316 children with WD, 199 were males and 117 were females, with the age of 5.4 (4.0, 7.6) years at diagnosis; 261 cases (82.6%) were asymptomatic with the age of 4.9 (3.9, 6.4) years; whereas 55 cases (17.4%) were symptomatic with the age of 9.6 (7.3, 12.0) years. The main symptoms invloved liver, kidney, nervous system, or skin damage. Of all the patients, 95.9% (303/316) had abnormal liver function at diagnosis; 98.1% (310/316) had the serum ceruloplasmin lever lower than 200 mg/L; 97.7% (302/309) had 24-hour urine copper content exceeding 40 μg; only 7.4% (23/310) had positive corneal K-F rings, 8.2% (23/281) had abnormal MRI signals in the lenticular nucleus, and all of them had symptoms of damage in liver, kidney or nervous system. Compared with the group of symptomatic WD, asymptomatic group had higher levels of serum alanine aminotransferase and lower levels ceruloplasmin and 24-hour urine copper [(208±137) vs. (72±78) U/L, (55±47) vs. (69±48) mg/L, 103 (72, 153) vs. 492 (230, 1 432) μg; t=9.98, -1.98, Z=-4.89, all P<0.001]. Among the 314 patients completing genetic sequencing, a total of 107 mutations in ATP7B gene were detected, of which 10 are novel variants, and 3 cases (1.0%) had large heterozygous deletion (exons 10 to exon 11) in ATP7B gene. The percentage of missense mutation in asymptomatic WD children was significantly higher than that in symptomatic WD (81.5% (422/518) vs. 69.1% (76/110), χ²=8.47, P<0.05). WD patients carrying homozygous variant of c.2 333G>T had significantly low levels of ceruloplasmin than those not carrying this variant ((23±5) vs. (61±48) mg/L, t=-2.34, P<0.001). Conclusions: The elevation of serum ALT is an important clue for early diagnosis of WD in children, while serum ceruloplasmin and 24-hour urine copper content are specific markers for early diagnosis of WD. In order to confirm the diagnosis of WD, it is necessary to combine the Sanger sequencing with multiplex ligation-dependent probe amplification or other testing technologies.

Fenótipo distinto da doença hepática gordurosa não alcoólica em pacientes com níveis reduzidos de cobre livre e ceruloplasmina / Distinct phenotype of non-alcoholic fatty liver disease in patients with low levels of free copper and of ceruloplasmin

ABSTRACT BACKGROUND: Copper deficiency has been linked to alterations in lipid metabolism and hepatic steatosis. Oxidative stress plays a role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). One of the enzymes that neutralize oxidative stress is Cu/Zn superoxide dismutase, which depends on the availability of adequate amounts of copper. OBJECTIVE: Correlate the levels of ceruloplasmin and of non-ceruloplasmin-bound copper (NCBC) with clinical, biochemical and histological parameters of non-alcoholic fatty liver disease (NAFLD) patients. METHODS: Data from 95 consecutively admitted NAFLD patients who underwent liver biopsy composed the groups based on ceruloplasmin levels lower than 25 mg/dL and on negative NCBC. The risk factors for NAFLD in each group were compared. RESULTS: Body mass index was lower in patients with ceruloplasmin <25 mg/dL (29.1±3.47 vs 32.8±6.24 kg/m2; P=0.005) as were the levels of LDL, HDL and total cholesterol, when compared with their counterparts with ceruloplasmin >25 mg/dL (101±38 vs 116±35 mg/dL, P=0.05; 43±9 vs 51±16 mg/dL, P=0.01; 174±43 vs 197±39 mg/dL, P=0.01, respectively). Mean serum ferritin levels were higher in the ceruloplasmin <25 mg/dL group (343±327 vs 197±190 ng/mL; P=0.02). Otherwise, patients with negative NCBC had higher HOMA-IR (8.2±14.7 vs 4.6±3.7; P=0.03). Age, gender, hypertension and diabetes showed no statistical difference. CONCLUSION: Patients with NAFLD had different clinical and biochemical markers according to the levels of NCBC and ceruloplasmin.

RESUMO CONTEXTO: A deficiência de cobre tem sido relacionada a alterações no metabolismo lipídico e esteatose hepática. O estresse oxidativo desempenha um papel fundamental na fisiopatologia da doença hepática gordurosa não alcoólica. Uma das enzimas que neutralizam o estresse oxidativo é a Cobre/Zinco superoxido dismutase, que depende da disponibilidade de quantidades adequadas de cobre. OBJETIVO: Correlacionar os níveis de ceruloplasmina e de cobre não ligado à ceruloplasmina (NCBC) com parâmetros clínicos, bioquímicos e histológicos de pacientes com doença hepática gordurosa não alcoólica (DHGNA). MÉTODOS: Dados de 95 pacientes com DHGNA internados consecutivamente e submetidos à biópsia hepática compuseram os grupos com base em níveis de ceruloplasmina inferiores a 25 mg/dL e em NCBC negativo. Os fatores de risco para DHGNA em cada grupo foram comparados. RESULTADOS: O índice de massa corporal foi menor nos pacientes com ceruloplasmina <25 mg/dL (29,1±3,47 vs 32,8±6,24 kg/m2; P=0,005), assim como os níveis de LDL, HDL e colesterol total, quando comparados aos seus pares com ceruloplasmina >25 mg/dL (101±38 vs 116±35 mg/dL, P=0,05; 43±9 vs 51±16 mg/dL, P=0,01; 174±43 vs 197±39 mg/dL, P=0,01, respectivamente). Os níveis médios de ferritina sérica foram maiores no grupo ceruloplasmina <25 mg/dL (343±327 vs 197±190 mg/mL; P=0,02). Os pacientes com NCBC negativo apresentaram maior HOMA-IR (8,2±14,7 vs 4,6±3,7; P=0,03). Idade, sexo, hipertensão e diabetes não mostraram diferença estatística. CONCLUSÃO: Pacientes com DHGNA apresentaram diferentes marcadores clínicos e bioquímicos de acordo com os níveis de NCBC e ceruloplasmina.

Proteinograma sérico, com ênfase em proteínas de fase aguda, de bovinos sadios e bovinos portadores de enfermidade aguda de ocorrência natural / Serum proteinogram emphasizing acute phase proteins from healthy and acute naturally occurring diseased cattle

Nas últimas décadas, as proteínas de fase aguda (PFAs) tornaram-se biomarcadores de escolha em medicina humana para identificação e monitoração de doenças. Não há razão para imaginar que tais pesquisas clínicas não sejam igualmente úteis na medicina veterinária. Com o objetivo de verificar a importância das PFAs como biomarcadores de doenças inflamatórias em bovinos, determinou-se o proteinograma sérico, por meio da técnica de eletroforese SDS-PAGE, com interesse especial nas PFAs. Foram utilizados 30 animais, distribuídos em dois grupos: 15 bovinos sadios e 15 bovinos doentes (cinco com mastite estafilocócica, cinco com fotossensibilização e cinco com onfaloflebite). Os animais foram submetidos a colheitas diárias de sangue durante sete dias, enquanto internados no Hospital Veterinário da Unesp, Campus de Jaboticabal. Ceruloplasmina e haptoglobina apresentaram elevação significativa em animais acometidos por mastite, fotossensibilização e onfaloflebite (275,17% e 343,71%; 175,17% e 230,19%; 114,47% e 144,47%, respectivamente). A α1-glicoproteína ácida foi um bom biomarcador apenas em animais com mastite e fotossensibilização, elevando, respectivamente, suas concentrações séricas em 198,14% e 145,89%. Fibrinogênio mostrou-se um indicador confiável apenas em bovinos com mastite, com elevação de 146,5% em relação ao grupo sadio. Ficou clara a diferença na responsividade de distintas PFAs frente a diferentes estímulos inflamatórios. Ceruloplasmina e haptoglobina foram biomarcadores mais sensíveis e, portanto, mais confiáveis entre as PFAs estudadas nessa espécie.

Over the last few decades acute phase proteins (APP) have become the biomarkers of choice in human medicine to identify and monitor inflammation and infection. There is no reason to suppose that clinical investigations in veterinary medicine would not be equally assisted by APP assays. Aiming to verify the importance of APPs as biomarkers of inflammatory diseases in domestic cattle, serum protein profiles, especially APPs, were determined through the SDS-PAGE electrophoresis technique. Thirty animals were allotted in two groups: 15 healthy cattle and 15 clinically ill cattle (5 with staphylococcal mastitis, 5 with photosensitization and 5 with onphalophlebitis). All animals were submitted to daily blood sampling during 7 days, while interned in the Veterinarian Hospital from UNESP, Jaboticabal campus. Ceruloplasmin and haptoglobin were significantly elevated in animals with mastitis, photosensitization and onphalophlebitis (275.17% and 343.71%; 175.17% and 230.19%; 114.47% and 144.47%, respectively). α1-acid glycoprotein behaved as a good biomarker only in animals with mastitis and photosensitization, elevating respectively 198.14% and 145.89% of their serum levels. Fibrinogen was a reliable indicator only in animals undergoing mastitis, with a raise of 146.5%. The diverse responsiveness of different APP under distinct inflammatory stimuli was clear. Ceruloplasmin and haptoglobin were more sensible and, therefore, reliable biomarkers to the diseases studied in this species.

Doença de Wilson em crianças e adolescentes: como fazer diagnóstico precoce / Wilson's disease in children and adolescent: a key to an early diagnosis

A doença de Wilson é uma desordem autossômica recessiva do metabolismo do cobre, que leva à impregnação desse metal em diversos tecidos como o fígado, cérebro, córnea e rins. Tem prevalência de 1:40.000 e evolui de forma progressiva e fatal se não tratada. Seu diagnóstico depende de suspeição clínica e exames laboratoriais, podendo ser difícil nos pacientes assintomáticos ou com insuficiência hepática grave. A tríade clássica de apresentação é hepática, neurológica e oftalmológica. Na criança, a forma de apresentação mais comum é a hepática (aguda ou crônica). Os critérios diagnósticos são baseados na presença de ceruloplasmina baixa, cobre em urina de 24 horas e cobre livre elevados e avaliação oftalmológica à procura do anel de Kayser-Fleischer. O tratamento medicamentoso deve ser instituído o quanto antes, de forma a evitaremse as lesões teciduais do excesso de cobre, daí a grande importância do diagnóstico precoce. A droga de escolha é a D-penicilamina, mas é necessário o monitoramento de seus possíveis efeitos colaterais e eventuais pioras do quadro neuropsiquiátrico. Existem outras drogas, como a trientina, tetratiomolibdato e o zinco, que também têm efeito na redução do cobre orgânico. (AU)

Wilson disease is an authossomal recessive disorder of copper metabolism that leads to the impregnation of the metal in different tissues such as the liver, brain, cornea and kidneys. There is a prevalence of 1:40,000 and evolution is progressive and fatal if untreated. The diagnosis depends on clinical suspicion and laboratory tests, and may be difficult in situations such as the asymptomatic patients or with severe liver insufficiency. The classic triad presentation is the hepatic, neurological and ophthalmologic disease. In children, the most common is the hepatic (acute or chronic). The diagnosis criteria are based on the presence of low ceruloplasmine, elevated copper in 24-hour urine and high seric copper and ophthalmologic evaluation in search of Kayser Fleischer ring. The medication treatment must be established as soon as possible so as to prevent tissue lesions due to copper excess, hence the great importance of early diagnosis. The drug choice is the D-penicilamin, with careful monitoring of side effects and attention for occasional worsening of the neuropsychiatric state. There are other drugs as trientine, tetratiomolibdato and zinc that also have an effect on the reduction of organic copper. (AU)

GST null genotype and antioxidants: Risk indicators for oral pre-cancer and cancer.

Objectives : This study was undertaken to detect the gene polymorphism of detoxification enzymes and estimate the antioxidant enzyme status in patients with oral cancer, oral leukoplakia and oral submucous fibrosis (OSF). Materials and Methods : The GSTM1 and GSTT1 gene polymorphism was evaluated using polymerase chain reaction; the antioxidant enzyme was estimated using biochemical methods. Statistical analyses were performed using student t-test and odds-ratio to estimate relative risk (RR). Results : The RR at 95% confidence interval (CI) for GSTM1 and GSTT1 was statistically significant for all groups. The mean values of glutathione were significantly raised in all groups. The mean values of ceruloplasmin and malonaldehyde was statistically significant among cancer and OSF patients but was insignificant in smokers and cases with leukoplakia. Conclusion : Several genes perform the same function which implies the need to test for several genetic polymorphisms to identify individuals at high risk. The level of antioxidant enzymes correlate with the degree of oxidative damage. The need for further studies is emphasised.

Ceruloplasmina: determinación de su actividad ferroxidasa / Ceruloplasmin: measurement of serum ferroxidase activity

La Ceruloplasmina (Cp) es la principal proteína transportadora de cobre en circulación. Su concentración es abundante en plasma; se considera un reactante de fase aguda y su función fisiológica no se encuentra fehacientemente establecida. Fundamentalmente se sintetiza en los hepatocitos. También se encuentra en otros tipos celulares como monocitos, astrocitos y células de Sertoli. Su concentración sérica se utiliza en el diagnóstico diferencial de enfermedad de Wilson. La concentración total en plasma se considera igual a la suma de las concentraciones de apo y holo Cp, de manera que la cantidad de esta proteína determinada por un método inmunológico no indica que la enzima se encuentre presente solamente en su forma activa. Entonces, al utilizar esta metodología, se sobreestima la proteína funcionalmente activa. Existen diversos métodos para determinar su actividad. En este trabajo se describe un método automatizado para medir su actividad ferroxidasa que utiliza iones Fe2+ como sustrato. Los valores de referencia de actividad de Cp se diferenciaron estadísticamente entre el grupo de mujeres y el de hombres, siendo de 424-796 UI/L y 397-733 UI/L, respectivamente. Además, se obtuvo una correlación significativa entre la actividad ferroxidasa y la concentración proteica (r=0,7285; p<0,0001).

Ceruloplasmin (Cp) is the principal copper carrier in human plasma. It is an abundant protein that participates in the acute phase reaction to stress, but its physiological function is unknown. Althought Cp is synthesised predominantly in the liver, other cell types express the protein, including monocytes, astrocytes and Sertoli cells. The serum concentration of the copper protein ceruloplasmin has been an important diagnostic indicator of Wilson`s disease. Measurement of the total amount of Cp protein may not reflect Cp enzyme activity in the serum. The immunologic assay may lead to overestimation of the total amount of functional Cp in the serum due to this method's capacity to determine both the functional holo Cp and non-functional apo Cp. Several methods for determining ferroxidase activity have been reported. In this study, a method is described for automated measurement of the activity. In this method, Fe2+ ions are used as the substrate. The range for serum Cp ferroxidase activity in healthy persons was 424-796 UI/L for women, and 397-733 UI/L for men. Significant correlations between serum ferroxidase activity and Cp concentration (r=0,7285; p < 0,0001) were found.

Serum copper, zinc, ceruloplasmin and superoxide dismutase in Thai overweight and obese.

The serum copper, selenium, ceruloplasmin, superoxide dismutase (SOD) (specific activities of antioxidant enzymes), anthropometric measurements, including waist/hip ratio 51 male and 190 female overweight subjects (body mass index (BMI) > or = 25.0 kg/m2) compared with a 26 male and 83 female control group (BMI = 18.5-24.9 kg/m2) Thai volunteers who attended the Out-patient Department, General Practice Section, Rajvithi Hospital, Bangkok, for a physical check-up from March to October, 1998, were investigated. There was no age difference between the overweight group and the controls. All of the anthropometric variables, except the height of the overweight group, were significantly higher than those of the normal subjects. The medians of weight and waist/hip ratio of overweight and obese males were significantly higher than those of overweight and obese females. Serum ceruloplasmin, copper were statistically significantly higher in overweight subjects than in the controls. However, serum zinc and superoxide dismutase activity in the overweight group were found to be lower than in the control group. Higher serum ceruloplasmin, copper, zinc and superoxide dismutase activity were shown in the female overweight group than in the male overweight group. Ceruloplasmin was found to correlate positively with copper concentration but negatively related with superoxide dismutase enzyme activity. A negative correlation was found between serum copper and zinc concentrations in both sexes of the overweight and obese subjects. Low SOD activity found in the overweight and obese subjects might be caused by low zinc intake.

Copper and ceruloplasmin status in serum of prostate and colon cancer patients.

Serum copper and ceruloplasmin levels were estimated in 20 patients each of prostate and colon cancer. Although copper to ceruloplasmin ratio was not significantly altered, copper and ceruloplasmin levels were increased significantly in the cancer patients as compared to controls. Trace elements and free radicals have been implicated in the etiology of cancer. Hence determination of specific antioxidants (like ceruloplasmin) and trace elements (like copper) may be of value in the early diagnosis of prostate and colon cancer.

The effect of cigarette smoking on ceruloplasmin and C3 complement: risk of cardiovascular disease (atherosclerosis).

Serum ceruloplasmin, C3 complement and albumin in 119 male smokers and 65 male non-smoker; from a military unit in Bangkok were investigated in this study. The serum ceruloplasmin concentration was found to be significantly higher in smokers than in non-smokers. However, the serum albumin concentration in smokers was statistically significantly lower than in non-smokers. Significant associations were also found between ages, albumin levels and the quantity of cigarettes smoked. There was a significant positive correlation between serum ceruloplasmin and C3 complement concentrations. An association between the quantity of cigarettes smoked and albumin was also found, as well as a significant relationship between smoking and the quantities of cigarettes smoked to serum ceruloplasmin levels when smoking and the quantity of cigarettes smoked were taken as independent variables, and the serum ceruloplasmin levels as a dependent variable. This might suggest that high concentrations of the acute-phase protein, i.e. ceruloplasmin, might constitute a risk of developing atherosclerosis or cardiovascular disease in smokers.

Modelo experimental para el estudio de la molibdenosis y de la deficiencia primaria de cobre en ratas / Experimental model for the study of molybdenosis in the primary copper deficiency in rats

Con el objetivo de diferenciar los efectos producidos por la deficiencia primaria cobre y los provocados por el excesso de molibdeno se evaluó un modelo experimental en ratas. Sesenta ratas de destete (30 machos y 30 hembras) recibieron una dieta compuesta por 70 por ciento de leche entera en polvo (1 ppm Cu) y 30 por ciento de harina de maíz (0.8 - 1.5 ppm Cu). Los animales se dividieron en tres grupos conforme a la suplementación mineral recibida: deficiencia primaria de cobre (40 ppm Fe), molibdenosis (40 ppm Fe + 40 ppm Cu + 500 ppm Mo) y controles (40 ppm Fe + 40 ppm Cu). Se pesaron cada 14 días. Al cabo de 70 días de tratamiento se obtuvieron muestras de sangre para determinación de hematocrito y actividad sérica de ceruloplasmina y se sacrificaron para medir concentraciones hepáticas de Cu y Mo. El grupo deficiente en Cu tuvo valores significativamente inferiores en la actividad de ceruloplasmina. Las concentraciones hepáticas de Cu y Mo fueron superiores significativamente en los animales con molibdenosis. Se concluye que con niveles de Cu por encima de los requerimientos mínimos, la alimentación con alto contenido de Mo, no afecta la actividad sérica de ceruloplasmina. Esto sumado a la concentración hepática de Mo lograda, permitirá identificar efectos "per se" de la molibdenosis.

Correlación imagenológica por resonancia magnética cerebral de manifestaciones neurológicas y oculares en la enfermedade de Wilson / Cerebral MR imaging correlation of neurological and ocular disorders in Wilson's disease

La enfermedad de Wilson o degeneración hepatolenticular es un defecto en el metabolismo del cobre que ocasiona su acumulación en diferentes tejidos, siendo el hígado, cerebro, riñón, ojo, y esqueleto óseo los más afectados. Los signos oftalmológicos de esta entidad consisten en un anillo corneal (Kayser-Fleischer) y cataratas floriformes. Se presenta el caso de un paciente femenina de 35 años en quien se manifestaron alteraciones motoras, cambios oculares como el anillo corneal y modificación en la amplitud de convergencia, hipercupremia e imágenes obtenidas por resonancia magnética cerebral que explican las manifestaciones clínicas. La enfermedad de Wilson debe de ser conisderada como una posibilidad diagnóstica en sujetos con signología motora e hipercupremia, siendo la exploración oftalmológica del segmento anterior útil para documentar la afección ocular y la resonancia magnética cerebral para correlacionar el cuadro clínico neurológico

Role of Murraya koenigii (curry leaf) and Brassica juncea (Mustard) in lipid peroxidation.

The status of lipid peroxidation was investigated in rats fed M. Koenigii (curry leaf) and B. juncea (Mustard). Concentration of malondialdehyde showed a significant decrease, while hydroperoxides and conjugated dienes were significantly increased in liver and heart of both the experimental groups. SOD and catalase activity was found to be increased in liver and heart of both the spices administered groups. Glutathione levels in liver, heart and kidney were lowered in rats administered these spices. Glutathione reductase, glutathione peroxidase and glutathione S-transferase activity showed a sharp increase in the experimental groups compared to the controls.

Informe sobre hallazgos en algunas investigaciones de laboratorio en encefalitis equina venezolana / Report on finding; in somes reseachs of laboratory in encephalitis equine venezolane

En pacientes con encefalitis equina venezolana se estudiaron 20 muestras de sangre y 20 de líquido cefalo-raquídeo, determinándose en ambas. transaminasas oxalacéticas y piruvicas, dehidrogenasa láctica y proteínas por fraccionamiento electroforético. estas últimas en sólo 10 casos de LCR. Se determinó también calcio y ceruloplasmina en suero. En la sangre: en 12 casos se obtuvieron cifras bajas de calcio. En 3 casos se hallaron valores altos de ceruloplasmina. En 6 casos se o0bservaron cifras altas para la TGO. No se hallaron alteraciones para la TGP. ni para la dehidrogenasa láctica. 17 casos mostraron hipoproteinemia. 8 casos presentaron anormalidades en una u otra fracción globulínica. En el LCR: en 4 casos se observó aumento de la TGO y en 6 casos aumento de la dehidrogenasa láctica. No se hallaron alteraciones para la TGP. En las muestras hubo inversión del índice albúmino-globulínico, con marcado aumento de las globulinas beta y disminución de las albúminas

The effect of oral contraceptives on protein metabolism.

The effect on protein and amino acid metabolism of combined oral contraceptives (OC) containing 150 micrograms of laevonorgestrel and 30 micrograms of ethinyl oestradiol was studied in a group of 34 healthy non-lactating women. This was compared to an identical study conducted in another group of 19 subjects who used IUCDs for contraception, and also in two other groups of subjects who were given an additional multivitamin preparation on a daily basis (29 subjects) and on the days when OC was not taken (29 subjects). Assessments were made prior to, and during the third week of the 4th, 7th, and the 13th cycles of OC treatment. Results indicated that the ceruloplasmin and retinol binding protein underwent significant increases with OC usage, while sex hormone binding globulin concentration, on the other hand, remained unaffected. At the same time, a significant reduction of several of the plasma amino acid and plasma albumin concentrations was observed, suggesting that the increase in the visceral and other types of protein concentrations previously noted was due to increased hepatic protein synthesis rather than increased breakdown or excretion as result of OC intake. Interesting biochemical alterations and metabolic effects previously observed may well be related to this altered synthesis and release of proteins and/or protein binders as well as induction of certain metabolic enzymes from the liver.

Matabolismo do cobre e anemia / Copper metabolism and anemia

O cobre é cofator essencial de várias metaloenzimas envolvidas em reaçöes químicas responsáveis por uma série de funçöes biológicas importantes tais como produçäo de energia (citocromo e oxidase), inativaçäo e radicais livres (superóxido dismutase), oxidaçäo do ferro orgânico (ferro oxidase), síntese de catecolaminas (dopamina Beta oxidase), maturaçäo do colágeno-elastina (lisil oxidase), síntese de melanina (tirosina hidroxilase) e síntese de hemoglobina. Assim como o ferro, o cobre participa das reaçöes de óxido-reduçäo como doador de prótons. Um indivíduo adulto de 70 Kg contém cerca de 80 mg de cobre, a grande maioria nos tecidos hepáticos, renal , cardíaco e cerebral. No sangue o cobre é encontrado nas hemácias, na forma de superóxido dismutase e no plasma, como ceruloplasmina (90%) e ligado à albumina (5%) e certos aminoácidos livres (histidina, tronina e glutamina). Os níveis plasmáticos normais säo 81-147 µg/dl e 20-40 mg/dl respectivamente para cobre e ceruloplasmina. A excreçäo de cobre ocorre pela bile (0,14 - 0,83 µM/Kg/dia) e pela urina (0,47 - 0,94 µM/Kg/dia). O cobre é encontrado, em quantidades variáveis, na maioria dos alimentos, assim como contaminante natural da água. A ingestäo diária é cerca de 1 - 5 mg dos quais 35% é absorvido. As recomendaçöes da OMS säo de 30 µg/Kg/dia para adultos e de 40 µg/Kg/dia para crianças. Pacientes em alimentaçäo parenteral total devem receber 300 µg/dia, elevando-se para 400-500 µg/dia quando houver patologia relacionadas a perdas intestinais e diminuindo-se para 150 µg/dia em presença de colestase. O quadro de deficiência de cobre é caracterizado por níveis plasmáticos menores de 80 µg/dia para adultos e de 90 µg/dl, para crianças. Sinais e sintomas de deficiência de cobre säo usualmente vistos em pacientes com alimentaçäo parenteral prolongada sem suplementaçäo de cobre, crianças alimentadas por longo tempo com leite de vaca, prematuros, tratamento com d-penicilamina e estados hipoproteinêmicos como na síndrome de má absorçäo, desnutriçäo proteico-energética e síndrome nefrótica...

Serum copper and ceruloplasmin in pregnancy with anaemia.

Estimation of serum copper and ceruloplasmin was done in 25 non pregnant females, 25 healthy pregnant women followed from I to III trimester and 75 pregnant women with anaemia--25 in each trimester. Anaemia was further divided into mild, moderate and severe types (27, 32 & 16 cases respectively). Normal pregnancy was associated with progressive increase in serum copper and ceruloplasmin--values being highest in III trimester. All types of anaemias in pregnancy revealed statistically significant elevation of serum copper and ceruloplasmin when compared to corresponding gestational period in normal pregnancy.