Clinical features of Menkes disease(report of one case) / 临床神经病学杂志

Objective To investigate the clinical features of Menkes disease(MD)caused by ATP7A gene mutation.Methods Clinical data of one MD patient was retrospectively analyzed,and the literature on the MD cases was reviewed.Results The patient was a 7-month-old male.The initial symptoms were epilepsy,feeding difficulties and psychomotor retardation,followed by distinctive facial appearance,hair abnormality,pectus excavatum and hypotonia.Biochemical tests revealed reduced serum ceruloplasmin and copper.Brain MRI showed diffuse cerebral atrophy,cerebral dysplasia and subdural effusion.Genetic testing showed that there was a new hemizygous mutation c.2916+2(IVS14)T＞C in the ATP7A gene splicing site on the X chromosome,which verified that the mother was a heterozygous carrier with a normal phenotype.Conclusions MD often starts in infancy and childhood.MD may involve multi-system such as the nervous system and connective tissues,and should be diagnosed with genetic testing.

Research progress in ceruloplasmin regulation of lipid metabolism homeostasis / 上海交通大学学报（医学版）

Ceruloplasmin(Cp)is a crucial protein secreted by the liver and plays a vital role in regulating the distribution and transport of copper throughout the body,thereby maintaining copper homeostasis.Additionally,Cp functions as a significant enzyme known as ferroxidase,which is involved in iron metabolism within the body.Numerous studies have suggested a close relationship between Cp and metabolic disorders,such as diabetes and cardiovascular diseases.Recent research has also shed light on the involvement of Cp in the regulation of lipid metabolism.The various activities associated with lipid metabolism,including lipid synthesis,adipose hydrolysis,fatty acid oxidation,lipid transport,and absorption,collectively contribute to maintaining lipid homeostasis.Dysregulation of lipid metabolism can lead to metabolic disorders and cardiovascular complications.Cp regulates lipid metabolism through two main mechanisms.Firstly,Cp participates in the regulation of oxidative stress by modulating iron metabolism through its ferroxidase activity and involvement in redox reaction.Secondly,copper along with copper-dependent enzymes directly participates in the processes such as cholesterol metabolism,lipoprotein metabolism,and fatty acid synthesis.As a result,the role of Cp in maintaining the homeostasis of copper and iron allows it to regulate lipid metabolism by influencing copper or iron-dependent enzymes and related pathways.Although the correlation between Cp and lipid metabolism has been identified,an in-depth exploration of the precise mechanisms by which Cp governs lipid metabolism is warranted.This article provides an overview of the role of Cp in lipid metabolism and highlights the progress in related research,with the aim of providing new insights for the development and treatment of disorders related to lipid metabolism.

Actividades enzimáticas séricas de la ceruplasmina y la mieloperoxidasa en diabéticos tipo 2

Introducción: La diabetes mellitus tipo 2 se caracteriza por la hiperglucemia debido a la insuficiente producción de insulina de las células β. La mieloperoxidasa promueve el estrés oxidativo durante la inflamación y la ceruloplasmina se considera su inhibidor endógeno. Objetivo: Evaluar la relación entre la ceruloplasmina y la mieloperoxidasa, determinadas simultáneamente en el suero de pacientes diabéticos tipo 2. Métodos: Se estudiaron 362 pacientes diabéticos tipo 2 y 110 sujetos sanos. La actividad sérica de la ceruloplasmina se determinó por el método de Siotto; y el de la mieloperoxidasa, por el de Kraeisz. Resultados: El 72 % de los pacientes diabéticos tenían hiperglucemia y el 77 % presentaba obesidad abdominal. Las actividades de ambas enzimas se incrementaron significativamente en relación con el grupo control. El coeficiente de correlación de la actividad enzimática resultó bajo. El cociente RMPO/CP de los pacientes diabéticos superó el de los controles. La ceruloplasmina no inhibió la mieloperoxidasa. Conclusiones: Predominó la mieloperoxidasa, por tanto, no se manifestó el efecto inhibitorio de la ceruloplasmina. La elevada actividad de la mieloperoxidasa se asocia con un agravamiento del cuadro clínico del paciente diabético.

Introduction: Type 2 diabetes mellitus is characterized by hyperglycemia due to insufficient insulin production by β cells. Myeloperoxidase promotes oxidative stress during inflammation and ceruloplasmin is considered its endogenous inhibitor. Objective: To evaluate the relationship between ceruloplasmin and myeloperoxidase, determined simultaneously in the serum of type 2 diabetic patients. Methods: A total of 362 type 2 diabetic patients and 110 healthy subjects were studied. Serum ceruloplasmin activity was determined by the Siotto KM method and myeloperoxidase by the Kraeisz JE method. Results: 72% of diabetic patients had hyperglycemia and 77% had abdominal obesity. The activities of both enzymes were significantly increased relative to the control group. The correlation coefficient of enzyme activity was low. The ORMO/CP ratio of diabetic patients exceeded that of controls. Ceruloplasmin did not inhibit myeloperoxidase. Conclusions: Myeloperoxidase predominated, therefore, the inhibitory effect of ceruloplasmin was not manifested. The high activity of myeloperoxidase was associated with a worsening of the clinical picture of the diabetic patient.

A Cross-sectional study on oxidative stress markers in type 2 Diabetes Mellitus and their correlation with blood sugar levels

Background: Among major metabolic disorders of glucose metabolism, diabetes mellitus is the most common one, in which Insulin deficiency and insulin resistance are the common observations. It is a renowned fact that long-standing hyperglycaemia is associated with oxidative stress, caused by an increase in the reactive oxygen species. Adenosine deaminase(ADA) is a purine metabolic enzyme that degrades adenosine. Gamma-glutamyl transferase (GGT) maintains antioxidant levels by maintaining reduced glutathione in the cells. Ceruloplasmin is a known acute phase reactant. Aim: 1. To Study and compare the levels of Serum FBS, PPBS, ADA, GGT and Ceruloplasmin in T2DM patients and nondiabetic subjects. 2. To study the correlation between these parameters and blood sugar levels in cases. Materials and methods: A descriptive cross-sectional study was done at Subbaiah medical college in Shimoga, taking 50 T2DM patients and 50 controls. Serum levels of fasting blood sugar(FBS), Postprandial blood sugar (PPBS), Adenosine deaminase, Gamma-glutamyl transferase and Ceruloplasmin were estimated. Data were analysed in SPSS software 17 using independent student t test. p < 0.01 was considered significant. Results: Increased levels of ADA, GGT and ceruloplasmin in cases were found, and they were statistically significant. Pearson correlation of these inflammatory markers with FBS and PPBS showed a positive significant correlation.

Correlation between serum ceruloplasmin level and elevated impulsivity in elderly patients with Parkinson′s disease / 中国医师杂志

Objective:To investigate the correlation between serum ceruloplasmin level and elevated impulsivity in elderly patients with Parkinson′s disease (PD).Methods:227 elderly PD patients treated in Jinhua People′s Hospital from October 2019 to June 2021 were selected as the research objects. They were grouped according to the 75th percentile of serum ceruloplasmin. 0-75th percentile was defined as normal and >75th percentile was defined as high level. The differences of second-order and first-order factor scores of Barratt′s Impulsivity Scale Version 11 (BIS-11) between the two groups were observed. After balancing the general characteristics, the third part of Parkinson′s Disease Rating Scale (MDS-UPDRS), Hoehn&Yahr Scale, Addenbrooke Cognitive Examination Revised Edition (ACE-R), clinical treatment plan and other data, the correlation between ceruloplasmin and BIS-11 was observed.Results:According to the 75th percentile level of ceruloplasmin, 56 patients were included in the high-level group and 171 patients were included in the normal group. The level of ceruloplasmin, the ratio of female patients, MDS-UPDRS Ⅲ, Hoehn&Yahr Scale and ACE-R score in the high-level group were significantly higher than those in the normal group (all P<0.05). The second-order unplanned and corresponding first-order self-control and first-order self-knowledge complexity in the high-level group were higher than those in the normal group (all P<0.05). There was no significant difference in second-order attention, first-order attention, first-order cognitive instability, second-order motivation, first-order motivation, first-order stability and BIS-11 score between the two groups (all P>0.05). After removing the confounding factors by multifactor logistic analysis, ceruloplasmin was correlated with second-order unplanned and its corresponding first-order factors (self-control and self-knowledge complexity) (all P<0.05). Conclusions:The serum ceruloplasmin level in elderly PD patients is related to the elevated level of BIS-11 unplanned impulse.

Clinical analysis and literature review of Wilson's disease with onset of mental and behavior disorder / 中风与神经疾病杂志

@#To investigate the clinical and imaging features，diagnosis，treatment and prognosis of patients with wilson disease（WD）.Methods The clinical data of wilson's disease with mental and behavior disorder were analyzed.Results The patient started the disease at the age of 16.At the beginning of the disease，she was talking to herself，laughing and in a daze，which did not attract the attention of her family.The first diagnosis and treatment was not made until the age of 22.Brain atrophy and T-2 high signal in bilateral thalamus，brainstem，cerebellum，pontine arm and putamen were shown on head MRI.K-F ring was positive under slit lamp，ceruloplasmin <3 mg/dl.Gene detection showed ATP7B gene variation.Conclusion When patients start with mental,emotional，and cognitive disorders,accompanied by intracranial symmetrical lesions and combined with systemic multiple system damage，WD should be considered.K-F loop，ceruloplasmin and gene detection are helpful for early diagnosis and treatment.

Advance in diagnostic indicators of hepatolenticular degeneration / 国际儿科学杂志

Hepatolenticular degeneration, also known as Wilson disease(WD), is an autosomal recessive disease with copper excretion disorder caused by ATP7B gene mutation.At present, the global incidence of hepatolenticular degeneration is about 1/30 000, but the frequency of ATP7B gene mutation is about 1/90.WD mainly manifests clinically as acute and chronic liver disease, neurological damage and renal impairment, etc.It is a genetic disease that can be well controlled by early diagnosis and treatment, so early diagnosis and treatment are important.However, because of its complex genotype and phenotype, it is easy to be misdiagnosed and delayed treatment.There is no single diagnostic standard for diagnosis of WD at the moment.The Leipzig diagnostic scoring system is often used for diagnosis.In recent years, there has been a new supplement to the diagnostic methods of WD.Some studies have confirmed that measuring the concentration of ATP7B protein by using ATP7B peptide can be used as a new diagnostic method for hepatolenticular degeneration, which is helpful for early accurate diagnosis.

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.

Markers of Inflammation in Rheumatoid Arthritis and Osteoarthritis

Introduction: Rheumatoid arthritis is characterized by local and systemic effects of inflammation while osteoarthritis is aninflammatory degenerative disorder of joints. A wide range of inflammatory markers are implicated in pathogenesis of rheumatoidarthritis and osteoarthritis as a consequence of persistent imbalance between pro- and anti-inflammatory immune mechanisms,leading to chronic inflammation. Hence the present study is an attempt to estimate the levels of serum ceruloplasmin , C-reactiveprotein (CRP) and rheumatoid factor (RF) factor as inflammatory markers in serum of rheumatoid arthritis and osteoarthritispatients and compare them with normal healthy controls. Materials and Methods: Serum ceruloplasmin was estimated byspectrophotometric method while serum C-reactive protein and RA factor were detected using agglutination test in thirty patientsof rheumatoid arthritis ,osteoarthritis and age and sex matched healthy controls each were included in the study. Results:Significant increase in ceruloplasmin was observed (p<0.0001) in rheumatoid arthritis and osteoarthritis as compared to healthycontrols and in that especially ceruloplasmin was more elevated in rheumatoid arthritis than osteoarthritis. C-reactive proteinwas found to be positive in rheumatoid arthritis and osteoarthritis and none of the controls. RF factor was found positive inrheumatoid arthritis and none of the osteoarthritis and controls. Conclusion: There was increased level of serum ceruloplasmin inthe patients with rheumatoid arthritis and osteoarthritis. C-reactive protein and RF factor was found to be positive in rheumatoidarthritis while C-reactive protein was found to be positive in rheumatoid arthritis and osteoarthritis. These findings suggest apossible role of these inflammatory markers in the pathogenesis of rheumatoid arthritis.

Serum level of ceruloplasmin in patients with different liver diseases in Jilin, China / 临床肝胆病杂志

ObjectiveTo investigate the serum level of ceruloplasmin in patients with different stages and etiologies of liver diseases. MethodsA total of 1077 patients with liver diseases who were hospitalized in Department of Hepatology, The First Hospital of Jilin University, from January 2012 to January 2018 were enrolled, and the serum level of ceruloplasmin was analyzed for the patients with different liver diseases. The Kruskal-Wallis H test was used to compare the level of ceruloplasmin between the patients with virus-related liver diseases with different liver functional states, and a Spearman correlation analysis was used to investigate the correlation of ceruloplasmin with other biomarkers. ResultsIn the Wilson’s disease group, 97.6% (41/42) of the patients had a serum ceruloplasmin level of ＜0.2 g/L and 881% (37/42) had a level of ＜0.1 g/L. In the non-Wilson’s disease group, 24.3% (251/1035) of the patients had a ceruloplasmin level of ＜0.2 g/L and 0.2% had a level of ＜0.1 g/L. There was a significant difference in the serum level of ceruloplasmin between the patients with virus-related liver diseases with different liver functional states, and the patients with chronic viral hepatitis, severe viral hepatitis, and viral hepatitis cirrhosis had a significantly lower level than those with acute viral hepatitis and virus-related liver cancer (P=0005, P＜0.001, P=0.001, P=0.027, P＜0.001, and P=0.001). In the patients without Wilson’s disease, serum ceruloplasmin was positively correlated with albumin and prealbumin (r=0.068 and 0.091, both P＜0.05) and was negatively correlated with prothrombin time (r=-0.297, P＜0.05). ConclusionCeruloplasmin often decreases significantly in patients with Wilson’s disease, with a slight reduction in patients with other types of liver diseases. For these patients, it should be determined whether the reduction in ceruloplasmin is caused by hepatocyte injury or the presence of Wilson’s disease.

Clinical significance of serum CER, HA and FT3 in diagnosis of liver fibrosis in chronic hepatitis B patients / 解放军医学杂志

Objective To investigate the clinical significance of serum ceruloplasmin (CER), hyaluronic acid (HA) and free thyroxine 3 (FT3) in detecting liver fibrosis in patients with chronic hepatitis B (CHB). Methods One hundred and thirty-six cases of CHB patients, 44 cases of post-CHB cirrhosis patients, 20 cases with HBsAg-positive hepatocellular carcinoma (HCC), and 50 healthy controls were randomly selected from July 2014 to January 2018. Serum CER was detected by immune scattering turbidimetry, and direct chemiluminescence method was used for the detection of HA and FT3, one-way ANOVA analysis or rank sum test was used to compare the levels of serum CER, HA, FT3 and other related indexes between each group and the control group. Analysis of the correlation between CER, HA, FT3 and diagnosis model of liver fibrosis was performed and its results were analyzed using the receiver operating characteristic (ROC) curves. Results (1) The level of serum CER in severe CHB and decompensated liver cirrhosis group was significantly lower than that in control group (P<0.05). The concentration of HA in severe CHB and liver sclerosis groups was significantly higher than that in control group, and the difference was statistically significant (P<0.05). And the concentration of FT3 in cirrhotic group and HCC group was significantly different from that in control group (P<0.05). (2) CER was negatively correlated with APRI (r=-0.202, P=0.004) and FIB-4 (r=-0.200, P=0.006), HA was positively correlated with APRI (r=0.491, P<0.000) and FIB-4 (r=0.514, P<0.000), and FT3 was positively correlated with APRI (r=-0.246, P<0.001) and FIB-4 (r= 0.361, P<0.000). (3) The AUC (area under the curve) of FT3, HA and CER for the diagnosis of cirrhosis were 0.831, 0.826 and 0.668, respectively. In order from high to low, the diagnostic efficacy of the groups was CER+HA+FT3, HA+FT3, CER+HA and CER+FT3. Conclusion The levels of serum CER, HA and FT3 in patients with CHB are correlated with the degree of liver fibrosis, and has an important reference value for diagnosis of post-CHB cirrhosis.

Enfermedad de Wilson: reporte de caso / Wilson ́s disease: a case report

La enfermedad de Wilson es una condición genética autosómica recesiva poco frecuente. Se ha identificado el gen ATP7B como el que codifica la proteína transportadora de cobre y su deficiencia lleva al acúmulo del metal en el cerebro, hígado y otros órganos vitales. Su diagnóstico clínico precoz es esencial para mejorar la calidad de vida del paciente. A continuación, se presenta el caso de un paciente de 20 años, masculino, con un cuadro clínico de 2 años de evolución de desinhibición, impulsividad, anartria y apraxia de la marcha, movimientos distónicos faciales y en 4 extremidades. Al examen físico se evidenció el anillo de Kayser Flescher a nivel ocular. En Resonancia Magnética Encefálica hiperintensidad en ganglios de la base y mesencéfalo en T2. Ceruloplasmina en suero 4.08 mg/dL. Cobre sérico 26.03ug/dL y cobre en orina de 24 horas 224.30ug/ 24h. Se confirma el diagnóstico de Enfermedad de Wilson, tratándose con D- Penicilamina, evidenciándose una evolución adecuada, con mejoría notable del cuadro neurológico. El tratamiento precoz permite una evolución favorable temprana del paciente, disminuyendo las secuelas neurológicas secundarias a la enfermedad; de ahí la importancia del reporte del presente caso.(AU)

BackgroundWilson's disease is a rare autosomal recessive genetic condition. The ATP7B gene has been identified as the one that encodes the copper transport protein and its deficiency leads to the accumulation of metal in the brain, liver and other vital organs. Your early clinical diagnosis is essential to improve the quality of life of the patient. Following we present the clinical case of a 20-year-old male patient who since 2 years ago, presented disinhibition, impulsivity, anartria and gait apraxia, facial dystonic movements and in extremities. To the physical exam, Kayser Flescher ring was present. In Brain Magnetic Resonance hyperintensity in Basal Ganglia and Midbrain. Serum Ceruloplasmin 4.08. Serum Copper 26.03. Urinary Cupper 224.30. The diagnosis of Wilson's disease is confirmed, treating with D-Penicillamine, evidencing an adequate evolution, with notable improvement of the neurological symptoms. Early treatment allows a favorable early evolution of the patient, reducing the neurological sequelae secondary to the disease; so that the importance of the report of this case.(AU)

Ceruloplasmin and Alkaline Phosphatase Levels in Preterm Delivery

Introduction:Preterm birth (PTB) is a major determinant of neonatal mortality and morbidity. Preterm babies are prone to serious illness or death during the neonatal period.PTB is one of the unresolved problems in clinical obstetrics and one of the greatest threats to the developing fetus, there is need to determine predictive biomarker for preterm delivery. Therefore present study aimed to assess serum levels of ceruloplasmin and Alkaline phosphatase inpreterm and full-term delivery.Materials andMethods:The present study includes total 80 subjects that comprise forty women presenting with preterm onset of labor followed by delivery and forty women who delivered at term served as controls.Blood Samples from the subjects were obtained for ceruloplasmin and Alkaline phosphatase estimation, when patient was in labor.Serum ceruloplasmin and alkaline phosphatase measured spectrophotometrically. Serum ceruloplasmin was estimated by Herbert A Ravinand Henry et al.method. Serum alkaline phosphatase was estimated by Kinetic p-NPP method.Results:Serum ceruloplasmin levels were significantly increased (P<0.001) in preterm delivery as compared to full term delivery. Alkaline phosphatase levels are significantly increased in preterm delivery (p<0.001) as compared to full term delivery. Conclusion: Our study showed that elevated levels of ceruloplasmin and alkaline phosphatase may be associated with preterm delivery in asymptomaticpregnant women. The elevated ALP may be due to mild chronic subclinical infection which may be responsible for preterm delivery. Ceruloplasmin is acute phase reactant,increaseddue toanantioxidant defence mechanism against oxidative stress.

Association between various antioxidants in normals and chronic obstructive pulmonary disease, their alteration and impact of smoking and disease on levels of antioxidants

Background: There is total alteration of various antioxidants in response to the oxidative stress, which is one of the major patho-physiologic hallmarks in chronic obstructive pulmonary disease (COPD) development. This study aims to establish the correlation between different antioxidants in normals and COPD, study the alteration in the correlation due to COPD and smoking as well as the impact of COPD and smoking on antioxidants levels.Methods: Study comprises of 96 normals as group I and 96 COPD patients as group II. The antioxidants albumin (Alb), bilirubin (Bil), uric acid (UA) ceruloplasmin (Cp), glutathione peroxidase (GSHPx), catalase (CAT) and superoxide dismutase 3 (SOD3) were estimated.Results: Significant lower serum Alb, UA, SOD3 and increased serum Cp and GSHPx were found in Group II. Significant correlation was found between Alb and UA (r=0.24); Bil and UA (r=0.26); Alb and CAT (r=0.211) and SOD3 and CAT (r=0.318) in normals. However, these correlations were altered in COPD where Alb correlates with Bil (r=0.235); UA with CAT (r=0.203) and SOD3 with GSHPx (r=-0.27). The correlation between SOD3 and CAT remained unaltered. Similar correlation of UA with Alb and Bil was observed in nonsmoker normals and between SOD3 and CAT in smoker normals. In COPD, no correlation was seen in nonsmokers, while in smokers Alb correlates with Bil (r=0.316) and SOD3 with CAT (r=0.317).Conclusions: These alterations may have clinical ramifications in further understanding the pathogenesis of COPD and developing therapeutic approaches.

Cupremia y colesterolemia como factores de riesgo en pacientes con enfermedad de Alzheimer / Plasma levels of copper and cholesterol as risk factors in Alzheimer disease patients / Cupremia e colesterolemia como fatores de risco em pacientes com doença de Alzheimer

Se estudiaron 241 personas, 119 controles y 122 pacientes con enfermedad de Alzheimer (EA) subagrupados en tres categorías de acuerdo con el estadio clínico de la dolencia, con el objetivo de investigar la influencia de niveles elevados de cobre libre y colesterol plasmático como factores de riesgo para la EA. Las conclusiones obtenidas de los resultados indicaron que los pacientes expuestos a una combinación de alto colesterol y de cobre no unido a ceruloplasmina tuvieron mayor proporción de marcadores de estrés oxidativo (carbonilos proteicos, sustancias reactivas al tiobarbiturato, glutatión oxidado y descenso de antioxidantes totales en sangre), conjuntamente con un incremento de HDL-colesterol peroxidado y lipoproteína "a" que correlacionó con la gravedad de su cuadro. Lo mismo sucedió con la relación entre péptidos amiloides (1-40) y (1-42) en plasma y los valores del mini-test de estado cognitivo (MMSE). Se halló que una función de adición de efectos que cuantificó el daño por cobre libre y colesterol oxidado resultó directamente proporcional a la pérdida de desempeño cognitivo estimada por medio del MMSE. Esta función es de fácil determinación y puede considerarse un nuevo biomarcador para estudiar riesgo en poblaciones expuestas, apoyar el diagnóstico clínico, o evaluar la eficacia de estrategias terapéuticas en pacientes con EA.

Alzheimer disease (AD) patients (122) compared to control subjects (119) were studied to determine the role of chronic exposure of hypercholesterolemic plasma levels and free copper (not bound to ceruloplasmin) as biomarkers of progression for AD. Oxidative stress parameters, lipid profile, amyloid levels, and cognitive status were studied in all participants. Conclusions obtained indicated that patients exposed simultaneously to free copper and increased cholesterol levels present higher indicators of oxidative stress (protein carbonyls, thiobarbituric acid-reactive substances, decreased total antioxidant activity in plasma and elevated oxidized HDL-cholesterol). Lipoprotein "a" concentrations also correlated with the clinical progression of the disease. The ratio amyloid ß(1-40)/ß(1-42) in plasma inversely correlated with the cognitive performance estimated by the Mini-Mental State Examination Test (MMSE). A defined function that weighs the contribution of the deleterious effect produced by combined free copper and Ox-HDL-cholesterol exposure directly correlated with the loss of cognitive performance. Thus, this biomarker could be a new tool for the screening of large populations under risk, or may be a useful way to estimate the efficacy of therapeuti approaches in patients suffering AD.

Foram estudadas 241 pessoas, 119 controles e 122 pacientes com doença de Alzheimer (DA), agrupados em três categorias de acordo com o estágio clínico da doença, com o objetivo de investigar a influência de níveis elevados de cobre livre e colesterol plasmático como fatores de risco para a DA. As conclusões obtidas a partir dos resultados indicaram que os pacientes expostos a uma combinação de colesterol alto e de cobre não ligados à ceruloplasmina apresentaram maior proporção de marcadores de estresse oxidativo (carbonilos proteicos, substâncias reativas ao tiobarbiturato, glutationa oxidada e diminuição dos antioxidantes totais no sangue ), juntamente com um aumento da HDL-colesterol peroxidado e lipoproteína "a" que correlacionou com a gravidade de sua condição. O mesmo aconteceu com a relação entre os peptídeos amilóides (1-40) e (1-42) em plasma e os valores do mini-teste do estado cognitivo (MMSE). Verificou-se que uma função de adição de efeitos que quantificou o dano por cobre livre e colesterol oxidado resultou diretamente proporcional à perda de desempenho cognitivo estimada através do MMSE. Esta função é fácil de determinar e pode ser considerada um novo biomarcador para estudar o risco em populações expostas, apoiar o diagnóstico clínico ou avaliar a eficácia de estratégias terapêuticas em pacientes com DA.

Parâmetros hematológicos e bioquímicos de bezerros neonatos da raça Holandesa tratados com ferro suplementar / Hematological and biochemical parameters of neonatal Holstein calves supplemented with iron

A deficiência de ferro em bezerros neonatos está associada ao desenvolvimento de anemia, que favorece o aparecimento de outras enfermidades como pneumonia e diarreia. Avaliou-se o efeito da suplementação de ferro sobre o eritrograma, teores séricos de ferro, ceruloplasmina e transferrina, bem como o potencial para toxicidade do protocolo utilizado por meio da avaliação dos teores de ureia, creatinina e enzimas hepáticas. Para tal avaliação foram utilizados 40 bezerros neonatos da raça Holandesa, alocados em cinco grupos experimentais com oito animais em cada grupo, que foram submetidos aos seguintes protocolos: administração intramuscular de 5mL de solução fisiológica estéril no 5º dia de idade (grupo controle G1), e administração intramuscular de 5mL de ferro dextrano 10% nos seguintes momentos: no 5º dia de idade (G2); no 5o e no 20º dias de idade (G3); no 5o e no 30º dias de idade (G4) e no 5o, 20o e 45º dias de idade (G5). Foram coletadas amostras de sangue até 8 horas após o nascimento e aos 5, 10, 20, 30, 60 e 90 dias de idade para realização do eritrograma, avaliação dos teores séricos de ferro, ceruloplasmina, transferrina, ureia, creatinina, bilirrubina total e direta, e das atividades das enzimas aspartato aminotransferase (AST), fosfatase alcalina (ALP) e gamaglutamiltransferase (GGT). Os animais que receberam ferro suplementar apresentaram menor oscilação nos parâmetros eritrocitários, embora os animais do grupo controle não tenham desenvolvido anemia. Notou-se também aumento, embora não significativo, nos teores séricos de ferro e das proteínas de fase aguda ceruloplasmina e transferrina, cuja atividade está relacionada ao metabolismo desse mineral. Os teores séricos de ureia, creatinina, bilirrubina total e direta e as atividades das enzimas GGT, AST e ALP não foram influenciados pelos protocolos de administração de ferro suplementar. Os protocolos de tratamento empregados não ocasionaram hepatoxidade ou nefrotoxidade aos animais. Concluiu-se que a suplementação com ferro dextrano por via parenteral em bezerros que recebem outras dietas que não apenas leite não traz benefícios que justifiquem sua indicação, embora sejam necessários mais estudos que avaliem a influência da suplementação com ferro sobre o tempo necessário para a recuperação, custos com o tratamento e impacto sobre a vida produtiva dos animais na idade adulta.(AU)

Iron deficiency in newborn calves is associated with the development of anemia, which favors the development of other infirmities such as pneumonia and diarrhea. The present study evaluated the effect of iron supplementation on erythrogram, serum levels of iron, ceruloplasmin and tranferrin, as well as potential toxicity of the protocol used by means of evaluation of urea, creatinine and hepatic enzyme activities. 40 newborn Holstein calves were allocated into 5 experimental groups comprising 8 calves each, which were subjected to the following treatment protocols: intramuscular administration of 5mL of sterile saline on the 5th day of age (control group G1), intramuscular administration of 5mL of 10% dextran iron in the following moments: on the 5th day of age (G2); on the 5th and in the 20th day of age (G3); on the 5th and 30th day of age (G4); on the 5th, 20th and 45th days of age (G5). Blood samples were taken until 8 hours after birth and with 5, 10, 20, 30, 60, and 90 days of age, and subjected to hemogram, evaluation of serum levels of iron, ceruloplasmin, transferrin, urea, creatinine, total and direct bilirrubin, and serum activities of aspartate aminotransferase (AST), alcaline phosphatase (ALP), and gamma-glutamyltransferase (GGT). Calves that received iron supplementation at any time presented less variation in the erythrocyte parameters, although calves in the control group did not develop anemia. Serum concentration of iron and acute phase protein ceruloplasmin and transferrin, which activities are related to iron metabolism, also increased, although not significantly. Serum levels of urea, creatinine, bilirubins and activities of AST, ALP, and GGT were not influenced by the administration protocols used in this experiment. The results of the experiment led to the conclusion that the supplementation with parenteral dextran iron in calves that receive diets other than exclusive milk does not bring sufficient advantages to be indicated, although more studies are necessary to evaluate the influence of iron supplementation on the outcome of infections in newborn calves, especially its influence on cost of treatment, time necessary for discharge and impact on its productive life.(AU)

Serum concentrations of acute phase proteins in goats and ewes with naturally acquired Staphylococcus aureus mastitis / Concentração de proteínas de fase aguda em cabras e ovelhas com mastite de ocorrência natural causada por Staphylococcus aureus

Serum protein concentrations, including acute phase proteins (APPs), of goats and ewes with naturally acquired Sthaphylococcus aureus mastitis were determined by means of SDS-PAGE electrophoresis to evaluate the relevance of these APPs as biomarkers of the disease in these species. Fifteen healthy goats and 5 goats with naturally acquired staphylococci mastitis, as well as fifteen healthy ewes and 5 ewes with staphylococci mastitis were submitted to daily blood sampling during 7 days. In goats, an increase of 570%, 125%, 621%, and 279% in serum concentrations of ceruloplasmin, fibrinogen, haptoglobin and α1-acid glycoprotein, respectively, was observed. In sheep the increase in serum concentrations of ceruloplasmin, fibrinogen, haptoglobin and α1-acid glycoprotein was of 337%, 90%, 461%, and 225%, respectively. Our results indicate that these APPs have considerable potencial as early and sensible biomarkers of mastitis caused by S. aureus in goats and sheep.(AU)

O proteinograma, incluindo proteínas de fase aguda (PFAs), de cabras e ovelhas com mastite de origem natural causada por Staphylococcus aureus, foi determinado por meio de eletroforese em gel de poliacrilamida contendo dodecil sulfato de sódio (SDS-PAGE) a fim de avaliar a importância destas PFAs como biomarcadores da enfermidade nestas espécies. Amostras de sangue foram colhidas diariamente de cinco cabras e cinco ovelhas com mastite estafilocócica naturalmente adquirida, bem como de quinze cabras e quinzes ovelhas saudáveis durante 6 dias consecutivos. Nas fêmeas caprinas, foi verificado aumento dos teores séricos de ceruloplasmina (570%), fibrinogênio (125%), haptoglobina (621%), e α1-glicoproteína ácida (279%). Nas fêmeas ovinas as concentrações de ceruloplasmina, fibrinogênio, haptoglobina e α1-glicoproteína ácida elevaram-se em 337%, 90,9%, 461% e 225%, respectivamente. Os resultados permitem inferir que estas PFAs são marcadores sensíveis e precoces de mastite causada por S. aureus em cabras e ovelhas.(AU)

Neuro Wilson’s – An Alien Presentation.

Wilson’s disease is an Autosomal recessive disorder of inborn error of copper metabolism in liver which results in accumulation of copper in the liver, brain, kidneys, eye and other organs affecting commonly children and young adults. Its incidence varied from 33 to 68 per 100,000 in India and 1 in 30,000– 40,000 in worldwide population. Mainstay of diagnosis primarily depends on clinical features, biochemical parameters, presence of Kayser-Fleischer (KF) ring. A middle aged man referred as spinocerebellar ataxia was incidentally found to be an exclusive case of Neuro Wilson’s without involvement of the liver and hence we intend to report this case for its rarity.

Serum concentrations of acute phase proteins and immunoglobulins of calves with rotavirus diarrhea / Concentração sérica de proteínas de fase aguda e imunoglobulinas em bezerros acometidos por diarreia por rotavírus

The aim of the present study was to characterize changes in acute phase protein levels according to the occurrence of rotavirus diarrhea in calves in the first month of life. Blood and fecal samples were taken before colostrum intake and at 1, 2, 7, 15, 21 and 30 days of age from 24 Holstein calves allotted in three experimental groups: calves that did not present diarrhea (group A), calves that presented diarrhea, but tested negative for rotavirus in feces (group B), and calves that presented diarrhea and tested positive for rotavirus in feces (group C) (experiment 1). When the animals presented episodes of diarrhea, blood and fecal samples were taken at 24-hour intervals until the end of clinical signs (experiment 2). Serum proteins were separated by SDS-PAGE technique and rotavirus in feces was detected by PAGE. Data of experiment 1 were analyzed by ANOVA and Tukey's test, considered significant at P<0.05. Data of experiment 2 were subjected to the HSD test. Total protein, globulins, and IgG concentrations were lower in group C than in groups A and B. Ceruloplasmin and transferrin levels were higher in group C than in groups A and B. Serum concentrations of haptoglobin and α1-acid glycoprotein did not differ significantly between groups throughout the experimental period. Calves presented diarrhea between 10.4 and 14.6 days of age in group B, and between 10.3 and 14.6 days of age in group C. In the moments of diarrhea manifestation, least square means of IgA, haptoglobin and α1-acid glycoprotein concentrations did not differ significantly between groups B and C, but ceruloplasmin and transferrin concentrations were higher in group C than in group B, as opposed to what occurred with IgG levels. These findings show that optimizing passive immunity transfer of immunoglobulins decrease the likelihood of calves developing diarrhea caused by rotavirus. In addition, ceruloplasmin presents characteristics of a biomarker of rotavirus infection in calves.(AU)

O objetivo do presente estudo foi avaliar alterações nos teores de proteínas de fase aguda de acordo com a ocorrência de diarreia por rotavírus em bezerros no decorrer do primeiro mês de vida. Amostras de sangue e fezes de 24 bezerros da raça Holandesa foram coletadas antes da ingestão de colostro e com um, dois, sete, quinze, vinte um e trinta dias de idade, sendo os bezerros alocados em três grupos: bezerros que não apresentaram diarreia (grupo A), bezerros que apresentaram diarreia, mas foram negativos para a detecção de rotavírus nas fezes (grupo B) e bezerros que apresentaram diarreia e foram positivos para detecção de rotavírus nas fezes (grupo C) (experimento 1). Sempre que os animais apresentavam episódio de diarreia, amostras de sangue e fezes eram coletadas em intervalos de 24 horas até o término dos sinais clínicos (experimento 2). As proteínas séricas foram separadas por meio da técnica de SDS-PAGE e a pesquisa de rotavírus nas fezes foi realizada por meio da técnica de PAGE. Os resultados do experimento 1 foram analisados por meio de ANOVA e do teste de Tukey, considerado significativo quando P<0,05. Os dados do experimento 2 foram submetidos ao teste HSD. Os teores de proteína total, globulinas e IgG foram menores no grupo C que nos grupos A e B, os teores de ceruloplasmina e transferrina foram maiores no grupo C que nos grupos A e B e as concentrações séricas de haptoglobina e α1-glicoproteína ácida não diferiram significativamente entre grupos. Os bezerros manifestaram diarreia, em média, com 10,4 a 14,6 dias de idade no grupo B e com 10,3 a 14,6 dias de idade no grupo C. Nos momentos de manifestação de diarreia, os teores de IgA, haptoglobina e α1-glicoproteína ácida não diferiram significativamente entre os grupos B e C, mas os teores de ceruloplasmina e transferrina foram maiores no grupo C que no grupo B, oposto ao verificado para o teor de IgG. Esses achados mostram que a otimização da transferência de imunidade passiva de imunoglobulinas reduz a probabilidade de os animais apresentarem diarreia por rotavírus. Adicionalmente, a ceruloplasmina apresenta características de um biomarcador da infecção por rotavírus em bezerros.(AU)

Clinical and laboratory features and gene diagnosis of Menkes disease / 中华实用儿科临床杂志

Objective To explore the clinical and laboratory features,and gene diagnosis method of Menkes disease (MD).Methods The clinical and laboratory features and gene diagnosis method of 2 infants with MD were reviewed.Results (1) Clinical features:both infants mentioned in this article were male.Their clinical manifestations were both began at 3-4 months age,including peculiar kinky hair,pale skin,pudgy cheeks,inguinal hernia,vessel abnormality,epilepsy and mental retardation.(2) Laboratory features:the ceruloplasmin concentrations significantly reduced to be ＜ 20 mg/L and 47 mg/L,respectively.The magnetic resonance angiogram images of case 1 showed the abnormal tortuosity of his intracranial vessels.The magnetic resonance images of case 2 showed a rapid progress from normal to severe brain atrophy within half a year.(3) Gene diagnosis:the sequencing of ATP7A gene in case 1 showed a nonsense mutation of c.2110 C ＞ T.The pathogenicity of this mutation had not been reported previously at home and abroad.The sequencing of the gene panel without pathogenic mutation was detected in case 2.But the multiplex ligation-dependent probe amplification test showed a gross deletion of ATP7A gene containing 8-12 exons.This mutation had been documented as a pathogenic mutation of MD.Both mothers of 2 patients were heterozygous mutation carriers of normal phenotype.Conclusions MD is a multisystemic disease caused by ATP7A gene mutation resulting in copper metabolism disorder.MD is inherited as an X-linked recessive trait.MD is characterized by kinky hair,connective tissue abnormalities and progressive neurodegeneration.Clinical diagnosis can be made on the basis of clinical features,findings of blood biochemical examination,and radiological findings.Gene sequencing and multiplex ligation dependent probe amplification test are the main technique widely used for genetic diagnosis.