Serum Ceruloplasmin Concentrations Research Articles

Wilson’s disease: A Comprehensive Review of Genetics, Pathophysiology, Clinical Symptoms, Diagnostic Techniques and Current Treatment

Introduction: Wilson's disease (WD) is a genetic disease, inherited in an autosomal recessive manner, caused by a mutation in the ATP7B gene, which results in impaired excretion of copper in the bile. This causes the accumulation of copper in various tissues and organs, leading to their damage. The range and severity of symptoms are wide, so diagnosis is difficult and requires a high index of suspicion. The most common clinical symptoms are hepatic and neuropsychiatric symptoms. Diagnosis is based primarily on clinical suspicion, typical symptoms and reduced serum ceruloplasmin concentration. Treatment includes pharmacological therapies, and in some cases liver transplantation is necessary. Wilson's disease, if left untreated, inevitably leads to serious disability and death. Purpose of the work: This study aims to review and characterize the clinical and pathophysiological aspects of Wilson’s disease. Materials and methods: A comprehensive analysis of research papers available on PubMed, Google Scholar, Web of Science, Embase and Scopus was undertaken using the searchterms encompassing the following keywords: Wilson’s disease, Copper metabolism, Copper toxicity, ATP7B, Ceruloplasmin, Gene Mutation Results: Wilson's disease is a rare genetic disorder that can lead to severe disability and even death. For this reason, rapid diagnosis and appropriately selected and individualized treatment play a key role. Wilson's disease remains a major diagnostic challenge, but new techniques for its diagnosis, such as genotype analysis, mainly through sequencing, as well as newborn screening, may significantly improve patient prognosis in the future.

Serum ceruloplasmin oxidase activity: A neglected diagnostic biomarker for Wilson disease

BackgroundLow serum ceruloplasmin concentration is considered robust marker for Wilson disease (WD) screening, measuring serum ceruloplasmin oxidase activity might be an even more valuable diagnostic tool, but it has not been sufficiently studied. MethodsAll patients who were assessed for serum ceruloplasmin oxidase activity between January 1, 2016, and September 2, 2019, were enrolled in this study. The diagnostic performance of serum ceruloplasmin oxidase activity was analyzed using receiver operating characteristic curve analysis (ROC), Spearman's rank correlation, and Mann-Whitney U test. ResultsSerum ceruloplasmin oxidase activity was significantly decreased in WD patients (0.87 U/L, IQR 0.61–1.54). The optimal cut-off of serum ceruloplasmin oxidase activity to identified WD is 7 U/L, with sensitivity and specificity of 97.03 % and 98.19 %, respectively. Furthermore, this study revealed a positive correlation between enzymatic and immunoreactive serum ceruloplasmin tests. As primary diagnostic methods, serum ceruloplasmin levels below the diagnostic cut-offs for either the enzymatic or immunoreactive tests were observed in 818 out of 842 WD patients (97.15 %). Compared with the presence of K-F rings in asymptomatic patients, the accuracy of serum ceruloplasmin tests was significantly higher (56.12 % VS 95.08 %). Moreover, the positive rate of cranial MRI in neurological patients was similar to the tests of serum ceruloplasmin (92.91 % VS 97.40 %). Moreover, 71 patients had ambiguous genetic results, complicating the diagnosis. However, serum ceruloplasmin tests successfully identified 65 out of these 71 patients (91.55 %). ConclusionSerum ceruloplasmin oxidase activity has excellent performance in diagnosing WD, which should be widely used as preferred test in WD patients.

Comprehensive insights into Menkes disease: Genetics, pathophysiology, animal models, diagnosis, and therapeutic strategies

Menkes disease (MD) is an inherited disorder affecting primarily the males which is X-linked recessive in inheritance pattern due to mutation in ATP7A gene that codes for copper transporter protein. This results in neurological complications and connective tissue lesions that make affected males succumb to death. MD can be classified as the classical and Occipital Horn Syndrome (OHS) varieties, though the severity and early presentation of the classical MD is more pronounced. Diagnostic assays include determination of serum copper and ceruloplasmin concentrations; neurochemical studies are also performed. The standard treatment usually entails the use of copper supplements with copper – Histidine being one of the most effective. Therefore, it is necessary to investigate the molecular pathophysiology of ATP7A disorder to come up with different therapies. Animal models such as zebrafish, fruit flies etc. are beneficial to know about MD pathology to get treatment. In summary, the early and accurate diagnosis of MD, followed by immediate treatment, plays a critical role in successful management of the disorder.

Brain and the whole-body bone imaging appearances in Menkes disease: a case report and literature review

BackgroundMenkes disease (MD) is a rare, inherited, multisystemic copper metabolism disorder. Classical Menkes disease is characterized by low serum copper and ceruloplasmin concentrations, leading to multiple abnormalities in the whole-body, especially in connective tissue and central nervous system. However, serum copper and ceruloplasmin levels are not reliable diagnostic biomarkers due to the low concentrations in healthy newborns either. The featured imaging manifestations play an important role in diagnosing Menkes disease. To our knowledge, there are few reports on the systemic imaging manifestations of Menkes disease.Case presentationA 4-month-old male patient presented with recurrent seizures. He had cognitive, intellectual, growth, gross motor, precision movement, and language developmental lags. The patient’s hemoglobin and serum ceruloplasmin level were low. On MRI, increased intracranial vascular tortuosity, cerebral and cerebellar atrophy, white matter changes, and basal ganglia abnormalities were observed. Plain radiograph revealed wormian bones, rib flaring, metaphyseal spurring, and periosteal reactions in the long bones of the limbs. A pathogenic variant in ATP7A gene was identified in the patient, so he was confirmed the diagnosis of Menkes disease. His symptoms did not improve despite symptomatic and supportive treatment during his hospitalization. Unfortunately, the infant died 3 months after leaving hospital.ConclusionA comprehensive and intuitive understanding of the disease’s imaging manifestations can help clinicians to identify the disease and avoid delays in care.

Germanium citrate improves ovarian granulosa cells viability and antioxidant defense system in aging female mice during endotoxemia

The study aimed to investigate the vitality of ovarian granulosa cells (GCs), metabolic activity of neutrophils, as well as the antioxidant system state in aging female mice subjected to experimental endotoxemia, as well as the influence of germanium (Ge) citrate on the studied parameters under these conditions. Treatment with Gramm-negative bacteria lipopolysaccharide caused pathological changes in mouse ovaries: a decrease in GCs viability by increasing necrosis, an enhancement of metabolic activity of peripheral blood neutrophils, an increase in lipid peroxidaxion products and a violation of the antioxidant defense system (as evidenced by an elevation of the content of reactive products of 2-thiobarbituric acid and a reduction of reduced glutathione in liver homogenate, as well as a decrease in the concentration of ceruloplasmin in blood serum of aging female mice). Pretreatment of mice with Ge citrate was effective to reduce GCs death and improve their viability, decrease the degree of disruption of the redox balance and weaken the activity of cells of non-specific immune protection in aging endotoxemic animals. Our results suggest that Ge citrate may offer promising therapeutic benefits. Its cytoprotective effects and regulatory role in the antioxidant defense system, combined with its potential to reduce the intensity of gram-negative bacterial toxins induced inflammation, imply its usefulness. This multifaceted action may help prevent ovarian cell aging and, consequently, improve reproductive function.

Determination of copper status by five biomarkers in serum of healthy women

BackgroundThe essential trace element copper is relevant for many important physiological processes. Changes in copper homeostasis can result from disease and affect human health. A reliable assessment of copper status by suitable biomarkers may enable fast detection of subtle changes in copper metabolism. To this end, additional biomarkers besides serum copper and ceruloplasmin (CP) concentrations are required. ObjectivesThe aim of this study was to investigate the emerging copper biomarkers CP oxidase (CPO) activity, exchangeable copper (CuEXC) and labile copper in serum of healthy women and compare them with the conventional biomarkers total serum copper and CP. Method and main findingsThis observational study determined CPO activity, the non CP-bound copper species CuEXC and labile copper, total serum copper and CP in sera of 110 healthy women. Samples were collected at four time points over a period of 24 weeks. The concentrations of total serum copper and CP were within the reference ranges. The comparison of all five biomarkers provided insight into their relationship, the intra- and inter-individual variability as well as the age dependence. The correlation and Principal Component Analyses (PCA) indicated that CP, CPO activity and total copper correlated well, followed by CuEXC, while the labile copper pool was unrelated to the other parameters. ConclusionsThis study suggests that the non-CP-bound copper species represent copper pools that are differently regulated from total copper or CP-bound copper, making them interesting complementary biomarkers to enable a more complete assessment of body copper status with potential relevance for clinical application.

Post-traumatic Stress Disorder: The Influence of the Environmental Context and Analysis of Oxidative Stress and Inflammatory and Glycemic Markers in Women Living in Kurdistan Regional Government-Iraq.

Background Internally displaced persons (IDP) camps are still home to a large number of female survivors of the Yazidi genocide carried out in Iraq in 2014 by the Islamic organization known as the Islamic State of Iraq and Syria (ISIS). Many of these women suffer from a persistent form of post-traumatic stress disorder (PTSD), which can last for many years. On the other hand, little is known about the intricate etiology of PTSD. Objectives In this observational cross-sectional study, the biochemical parameters, including inflammatory and oxidative stress (OXS) markers, were evaluated in two groups: the case group (women with newly diagnosed PTSD) and the control group (apparently healthy women). Furthermore, how the environment impacts the biochemical and OXS parameters of people not diagnosed with PTSD but living in IDP camps was also analyzed. Materials and methods The PTSD group (n=55, age=30.0 years) was made up of women survivors of genocide-related events living in IDP camps in the Kurdistan region of Iraq. The studied parameters in the PTSD group have been compared to two healthy control groups: (1) internal control group (n=55, age=28.1 years): healthy women living inside the IDP camps; and (2) external control group (n=55, age=28.3 years): healthy women living outside the IDP camps. The diagnosis of PTSD was conducted using a validated Kurdish version of the PTSD Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (PCL-5) scale. Blood samples were collected to determine the level of glycated hemoglobin (HbA1c) and the concentrations of fasting serum glucose (FSG), C-reactive protein (CRP), ceruloplasmin (CP), 8-hydroxydeoxyguanosine (8-OHdG), glutathione (GSH), malondialdehyde (MDA), protein carbonyls (PC), and catalase (CAT) activity. Results Women with PTSD presented increased values of FSG (4.41%, p<0.05), HbA1c (4.74%, p<0.05), and CRP (114.29%, p<0.05), as well as increased levels of 8-OHdG (185.97%, p<0.001), CP (27.08%, p<0.001), MDA (141.97%, p<0.001), and PC (63.01%, p<0.001), besides increased CAT activity (121.5%, p<0.001), when compared with the control groups. A significant reduction of GSH (-20.33%, p<0.05) was observed in PTSD patients as compared to the external control group. In relation to the internal control group, women diagnosed with PTSD presented significantly increased levels of FSG (3.88%, p<0.05), HbA1c (2.83%, p<0.05), CRP (77.97%, p<0.05), and PC (41.3%, p<0.05), as well as increased levels of 8-OHdG (118.84%, p<0.001), CP (22.72%, p<0.001), MDA (90.67%, p<0.001), and CAT activity (55.31%, p<0.001). Healthy individuals residing in IDP camps, compared with external healthy control, presented significantly elevated levels of 8-OHdG (30.68%, p<0.001), MDA (26.91%, p<0.001), PC (15.37%, p<0.001), and CAT activity (42.62%, p<0.001). Conclusion Our findings indicate that PTSD significantly influences glycemic, inflammatory, oxidant, and antioxidant parameters, as evidenced by increased levels of FSG, HbA1C, CRP, PC, MDA, 8-OHdG, and CP, as well as increased CAT activity and a reduced GSH concentration in the PTSD group in comparison to the external control group. Additionally, our results suggest that the environmental context in IDP camps by itself can potentially affect oxidant and antioxidant parameters, as evidenced by the increased concentrations of 8-OHdG, MDA, and PC and increased CAT activity found in individuals not diagnosed with PTSD but living inside the camps.

Tocilizumab, a Humanized Anti-interleukin-6 Receptor Antibody, Induces Hepatic Iron Overload in a Susceptible Patient.

A 75-year-old woman visited to our hospital with liver dysfunction. The patient's liver function was normal. She had been treated with tocilizumab for rheumatoid arthritis for two years. One year after initiation of tocilizumab treatment, liver dysfunction was observed. serum ceruloplasmin concentration was low. We diagnosed hepatic iron overload because of a high ferritin concentration and a liver biopsy. The cessation of tocilizumab and phlebotomy improved the liver function. We believe that tocilizumab induced iron accumulation. We should be aware of the possibility that tocilizumab induces iron overload in susceptible patients and monitor iron status in patients treated with tocilizumab.

Ceruloplasmin and some biochemical parameters as a marker for acute myeloid leukemic patients

Acute myeloid leukemia is a second type of leukemia and has more effect on elder patients than adult. This research's objective was to measure the serum levels of ceruloplasmin (CP), ferritin (FR), vitamin B12 (VitB12), folic acid (FA), zinc (Zn), copper (Cu), and iron (Fe) in acute myeloid leukemic patients (AML) (before and after taking chemotherapy) and healthy control groups. In this study, about (160) blood samples (males and females) were collected from acute myeloid leukemic patients in Erbil’s Nanakali hospital and they were separated into four groups: Group 1 (G1) including (40) Apparently healthy control group, Group 2 (G2) include (40) acute myeloid leukemic patients before taking chemotherapy (new cases), Group 3 (G3) include (40) acute myeloid leukemia patients taking chemotherapy for one cycle, and Group 4 (G4) include (40) acute myeloid leukemic patients with taking chemotherapy for more than one cycle. The outcomes display a significant increase in serum concentration of ceruloplasmin, ferritin, vitamin B12, and iron in all patient groups when compared with control groups. While the serum concentration of folic acid, zinc, and copper decreased in all patient groups when compared with the healthy control group. In addition, the correlation analysis displays that there was a significant positive correlation between ceruloplasmin with ferritin, vitamin B12, and iron, on another hand have a non-significant negative correlation between ceruloplasmin with folic acid, zinc, and copper. According to the present study, there was a direct correlation between AML patients with the serum levels of CP, FR, VitB12, FA, Zn, Cu, and Fe. A high area under the curve of our data suggests that testing for (CP, FR, VitB12, FA, Cu, and Fe) could be helpful to detect AML. However, zinc is not a good biomarker for detecting AML patients.

Effect of Recommended Dietary Intake versus Higher Doses of Supplemental Zinc on Iron and Copper Deficiency Anemia Among Patients with Chronic Kidney Diseases, A Double-Blinded, Randomized Clinical Trial

Background: Complex interplays happen in absorption and function of iron, zinc and copper. Both zinc deficiency and excess may lead to anemia. In Iran, commonly available supplements for chronic kidney disease (CKD) patients contain 25 mg-zinc (Zn). This study compared 25 mg versus 7.5 mg dose of zinc in anemia of CKD patients, the latter dose approximates to recommended dietary intake (RDI) of zinc. Methods: In this double-blinded clinical trial, 51 non-dialysis CKD patients were randomized to continue previous formulation (25 mg-Zn group) or change to a new preparation (7.5 mg-Zn group) for three months. Blood counts and serum iron, zinc and copper status were compared between and within the groups. Results: At the end of the study, serum copper and ceruloplasmin concentrations were significantly higher in 7.5 mg-Zn group compared with those in 25 mg-Zn arm (115.04± 23.05 vs. 102.48±14.98 µg/dL; P= 0.02 and 29.97±7.94 vs. 25.42±4.23 mg/dL; P= 0.01, respectively). Serum zinc levels did not differ between two groups (76.73±15.35 vs. 77.68±18.07 µg/dL for 7.5 mg-Zn and 25 mg-Zn groups, respectively; P= 0.84). After three months, patients in 7.5 mg-Zn group experienced increase in their Hb (11.11±1.17 vs. 10.72±1.03 g/dL; P= 0.04), HCT (35.28± 4.01 vs. 33.96± 3.74%; P= 0.03), MCV (86.30 (81.40-90.82) vs. 86.00 (80.35-88.77) ¦L; P= 0.01) and ferritin (202.60 (79.29-298.97) vs. 129.07 (42.25-225.87) ng/mL; P&lt;0.001) compared to their baseline values. Conclusion: Reducing zinc content to its RDI value in supplement for CKD patients led to increased serum copper and ceruloplasmin concentrations. Moreover, patients who switched to RDI zinc-containing formula experienced a significant rise in blood hemoglobin. hematocrit, mean corpuscular volume (MCV), and ferritin concentration.

Effect of the Acute Total Gamma Radiation in a Sublethal Dose on the Biophysical Properties of Red Blood Cells, Lipid Peroxidation, Antioxidant Supply and Hemocoagulating Properties of Erythrocytes

Abstract The aim of the investigation was to study the effect of acute, total gamma-irradiation in a sublethal dose on the biophysical properties of erythrocytes, the intensity of lipid peroxidation, antioxidant supply and hemocoagulating properties of erythrocytes. The experiments were carried out on 11-12-week-old age guinea pigs, males and females in equal numbers. The animals were exposed to a single total radiation at a dose of 4.5 Gy (sublethal dose, LD 50/30). The studies were carried out on the 7th day after exposure to radiation (at the height of radiation sickness). The development of radiation damage was accompanied by intense erythropoiesis and the appearance of erythrocytes with a high resistance to hemolysis and an increased sedimentation rate. After acute gamma irradiation, depletion of the antioxidant system was noted. It manifested in a decrease in the activity of superoxide dismutase of erythrocytes by 19.7% (p&lt;0.01) and the concentration of serum ceruloplasmin by 21.5% (p&lt;0.01). The content of thiobarbituric acid reactive substances (TBARS) and their accumulation while the incubation of erythrocytes remained within the normal range. The erythrocytes of the irradiated animals exhibited increased procoagulant and decreased antiheparin activity, which reflects conformational changes in highly radiosensitive fatty acid chains of phospholipids in their membranes. A decrease in the fibrinolytic activity of erythrocytes in irradiated animals was found.

Monitoring of Copper in Wilson Disease.

(1) Introduction: Wilson's disease (WND) is an autosomal recessive disorder of copper (Cu) metabolism. Many tools are available to diagnose and monitor the clinical course of WND. Laboratory tests to determine disorders of Cu metabolism are of significant diagnostic importance. (2) Methods: A systematic review of the literature in the PubMed, Science Direct, and Wiley Online Library databases was conducted. (Results): For many years, Cu metabolism in WND was assessed with serum ceruloplasmin (CP) concentration, radioactive Cu test, total serum Cu concentration, urinary copper excretion, and Cu content in the liver. The results of these studies are not always unambiguous and easy to interpret. New methods have been developed to calculate non-CP Cu (NCC) directly. New parameters, such as relative Cu exchange (REC), reflecting the ratio of CuEXC to total serum Cu, as well as relative Cu exchange (REC), reflecting the ratio of CuEXC to total serum Cu, have been shown to be an accurate tool for the diagnosis of WND. Recently, a direct and fast LC-ICP-MS method for the study of CuEXC was presented. A new method to assess Cu metabolism during treatment with ALXN1840 (bis-choline tetrathiomolybdate [TTM]) has been developed. The assay enables the bioanalysis of CP and different types of Cu, including CP-Cu, direct NCC (dNCC), and labile bound copper (LBC) in human plasma. Conclusions: A few diagnostic and monitoring tools are available for patients with WND. While many patients are diagnosed and adequately assessed with currently available methods, diagnosis and monitoring is a real challenge in a group of patients who are stuck with borderline results, ambiguous genetic findings, and unclear clinical phenotypes. Technological progress and the characterization of new diagnostic parameters, including those related to Cu metabolism, may provide confidence in the more accurate diagnosis of WND in the future.

Serum C-Reactive Protein, Procalcitonin and Ceruloplasmin Concentrations in Dogs with Naturally İnfected Ehrlichiosis

This study aimed to evaluate the concentrations of C-reactive protein (CRP), Procalcitonin (PCT), and ceruloplasmin (Cp), which are potential biochemical markers of the inflammatory process in dogs naturally infected with Ehrlichiosis. A total of 20 dogs, 8 clinically healthy (Healthy group) and 12 mono-infected with Ehrlichia spp. (Ehrlichia group) were included in the study. Dogs in the Ehrlichia group were selected from those showing clinical signs of active infection, and their diseases were diagnosed with commercial test kits. Serum CRP and PCT levels were analysed by commercially available test kits, and Cp concentration was determined by colourimetric methods. The CRP concentration in the Ehrlichia group was significantly higher compared to the healthy group. There was no significant difference between the groups in serum PCT and Cp concentrations. As a result, the increase in serum CRP concentration can be used for detecting inflammatory processes in dogs with Ehrlichiosis. In addition, this study showed that PCT and Cp concentrations are not clinically useful markers for determining inflammatory status in dogs with Ehrlichiosis.

Impact of Long-Term Cyclamate and Saccharin Consumption on Biochemical Parameters in Healthy Individuals and Type 2 Diabetes Mellitus Patients.

Previous studies on saccharin and cyclamate were either limited to experimental animals or lacked evaluation of their long-term consumption effects in humans. This study evaluated the effect of chronic consumption of saccharin and cyclamate on biochemical parameters in healthy individuals and patients with type 2 diabetes mellitus. Healthy and diabetic individuals were classified into two groups based on whether they consumed sweeteners or not. The participants were classified according to the amount of sweetener consumed per day and duration of consumption. Serum catalase activity, peroxynitrite, ceruloplasmin, and malondialdehyde concentrations were determined. Glycated hemoglobin, fasting glucose, creatinine, alanine transaminase, and lipid profile were also evaluated. The results suggest that saccharin and cyclamate increased HbA1C (+11.16%), MDA (+52.38%), TG (+16.74%), LDL (+13.39%), and TC/HDL (+13.11%) in healthy volunteers. Diabetic patients consuming sweeteners showed increased FSG (+17.51%), ceruloplasmin (+13.17%), and MDA (+8.92%). Diabetic patients showed a positive correlation between the number of tablets consumed per day with FSG and serum creatinine. A positive correlation was found between the duration of sweetener consumption and FSG as well as TG. Consumption of saccharin and cyclamate affected biochemical parameters related to metabolic functions in a time and dose-dependent manner and appear to increase oxidative stress in healthy and diabetic type 2 patients.

Wilson’s Disease with Late Hepatic Involvement

Wilson’s Disease (WD) is an autosomal recessive condition that affects copper metabolism and manifests itself clinically in different ways. The diagnosis is indicated by low serum copper and ceruloplasmin concentrations, increased urine copper excretion and/ or increased hepatic copper concentrations. The present case report is about a 55-year-old male with chief complaints of loss of appetite, abdominal swelling, tremors in hand and head, slurring of speech for 10 days. Ultrasound (USG) findings were suggestive of liver cirrhosis with portal hypertension and liver function tests were also deranged. He was prescribed diuretics and asked to review after 10 days. Kayser-Fleischer ring was observed through slit lamp examination in both the eyes, which is a hallmark of WD. The Magnetic Resonance Imaging (MRI) of brain also revealed positive findings-hyperintensity throughout the mesencephalon for WD. Thereafter, the patient was treated with penicillamine and his symptoms improved after few days

Acute Phase Proteins and Procalcitonin in the Modeling of Infectious Arthritis

Background. Acute phase proteins – ceruloplasmin, haptoglobin, C-reactive protein (CRP) – are markers that characterize the inflammatory process. C-reactive protein is one of the major components of the acute phase (AF) and is a generally accepted indicator of inflammatory processes.&#x0D; Objective: to determine the level and specificity of acute-phase proteins (CRP, haptoglobin, ceruloplasmin), as well as procalcitonin in the modeling of infectious arthritis.&#x0D; Materials and Methods. Experimental studies were carried out on 31 white male Wistar rats. The model of infectious arthritis was created during three days by daily injection of 0.02 ml of S.aureus 108 No. 209 into the knee joint of a rat. The animals were divided into groups, of which group I was the vivarium control. The following model of drug administration was used for the experimental groups: a single daily injection of 0.02 ml of flosteron into the knee joint for three days (group II); daily single administration for three days of 0.02 ml of S.aureus 108 No. 209 (group III); daily one-time alternating (every other day) administration for three days of 0.02 ml of flosteron and 0.02 ml of S.aureus 108 No. 209 into the knee joint (group IV). The effectiveness of the drugs was observed 3 and 14 days after administration.&#x0D; Results. It was established that the concentration of haptoglobin probably increased in the blood serum of rats after 3 days only under the conditions of alternating three-time administration of flosterone and S.aureus 108 No. 209. After 14 days, when the inflammatory progress progressed, this indicator increased in all studied groups of animals, and most of all (by analogy with observations after three days) with the combined effect of flosterone and S.aureus 108 No. 209. The concentration of ceruloplasmin in blood serum increased in all experimental rats both after 3 days and after 14 days in the group after administration of flosterone. The content of C-reactive protein in blood serum increased in all studied groups of rats without exception, which proves its high specificity for detecting inflammatory processes of various severity. The concentration of procalcitonin in the experiment did not reliably change in the blood serum of rats of any experimental group after 3 days. However, significant changes occurred 14 days after the introduction of flosterone and with the combined effect of flosterone and S.aureus 108 No. 209.&#x0D; Conclusions. Determining the content of haptoglobin is not highly effective in early detection of the inflammatory process. At the same time, the synthesis of ceruloplasmin increases precisely during the first three days of the infectious process, which turns it into an effective marker for detecting early infectious complications. The dynamics of changes in the level of C-reactive protein in blood serum demonstrated the highest correlation with the activity of the infectious process, which proves its high specificity for detecting inflammatory processes of various severity. The greatest deviations were observed in rats, which were injected three times alternately (every other day) with flosterone and S. aureus 108 No. 209 into the knee joint. Such changes suggest that the hormonal drug flosteron contributed to the intensification of the inflammatory process.

ЕFFICIENCY OF DETERMINATION OF ACUTE PHASE PROTEINS AND PROCALCITONIN UNDER THE CONDITIONS OF SIMULATING INFECTIOUS ARTHRITIS

Acute phase proteins ceruloplasmin, haptoglobin, C-reactive protein (CRP) and procalcitonin are markers that characterize the inflammatory process. C-reactive protein is one of the central components of the acute phase (AF) and is a generally accepted indicator of inflammatory processes. Aim. Determination of the level and efficiency of determination of acute-phase proteins (CRP, haptoglobin, ceruloplasmin), as well as procalcitonin under the conditions of modeling infectious arthritis. Materials and methods. Experimental studies were conducted on 52 white male Wistar rats. A model of infectious arthritis was created for seven days by daily injection of 0.02 ml of S.aureus 108 No. 209 into the knee joint of a rat. The animals were divided into groups - and vivarium control. The following model of drug administration was used for the experimental groups: a single daily injection of 0.02 ml of flosteron into the knee joint for seven days (group II); daily single administration for seven days of 0.02 ml of S.aureus 108 No. 209 (III group); daily one-time alternating (every other day) administration for seven days of 0.02 ml of flosteron and 0.02 ml of S.aureus 108 No. 209 into the knee joint (group IV). The effectiveness of the drugs was observed 3 and 14 days after administration. Results. It was established that the concentration of haptoglobin was significantly increased in the blood serum of rats both after 3 and 14 days in all studied groups of animals compared to the control. The greatest increase relative to the control values was noted 3 days after the seven-time injection of S.aureus 108 #209 into the knee joint. However, after 14 days it was already not so significant and significantly lower (by 85.33%) compared to the measurement after three days. Only in rats after a 14-day alternating (every other day) injection of 0.02 ml of flosteron and 0.02 ml of S.aureus 108 No. 209 into the knee joint was observed a probable increase in the level of haptoglobin by 775.08% (Р&lt;0.05) compared to the control and 77.78% reduced compared to the measurement after three days. The concentration of ceruloplasmin in blood serum increased in all experimental rats during the entire observation period and differed little between 3 and 14 days. The content of C-reactive protein in blood serum increased in all studied groups of rats without exception, which proves its high specificity for detecting inflammatory processes of various severity. The concentration of procalcitonin was most likely to increase by 235.0% 3 days after alternating (every other day) administration of 0.02 ml of flosterone and 0.02 ml of S.aureus 108 No. 209. It was slightly lower by 120.0% under the same conditions experiment after 14 days. This indicator probably increased by 65% 14 days after the 7-time introduction of S.aureus 108 #209. In the rest of the experimental animals, the PCT concentration did not change. Conclusions. The determination of haptoglobin reflects, first of all, the primary activation of the inflammatory process, which was enhanced by the hormonal drug flosteron. However, its determination can be effective over a longer period of time, as several factors lead to a bacterial infection, reinforcing each other. At the same time, the synthesis of ceruloplasmin increases precisely during the first three days of the infectious process, which turns it into an effective marker for detecting early infectious complications. The dynamics of changes in the level of C-reactive protein in blood serum showed the highest correlation with the activity of the infectious process, which proves its high efficiency for detecting inflammatory processes of various severity, choosing adequate treatment and predicting the course of the disease.

Abnormal concentrations of acetylated amino acids in cerebrospinal fluid in acetyl-CoA transporter deficiency.

Acetyl-CoA transporter 1 (AT-1) is a transmembrane protein which regulates influx of acetyl-CoA from the cytosol to the lumen of the endoplasmic reticulum and is therefore important for the posttranslational modification of numerous proteins. Pathological variants in the SLC33A1 gene coding for AT-1 have been linked to a disorder called Huppke-Brendel syndrome, which is characterized by congenital cataracts, hearing loss, severe developmental delay and early death. It has been described in eight patients so far, who all had the abovementioned symptoms together with low serum copper and ceruloplasmin concentrations. The link between AT-1 and low ceruloplasmin concentrations is not clear, nor is the complex pathogenesis of the disease. Here we describe a further case of Huppke-Brendel syndrome with a novel and truncating homozygous gene variant and provide novel biochemical data on N-acetylated amino acids in cerebrospinal fluid (CSF) and plasma. Our results indicate that decreased levels of many N-acetylated amino acids in CSF are a typical metabolic fingerprint for AT-1 deficiency and are potential biomarkers for the defect. As acetyl-CoA is an important substrate for protein acetylation, we performed N-terminal proteomics, but found only minor effects on this particular protein modification. The acetyl-CoA content in patient's fibroblasts was insignificantly decreased. Our data may help to better understand the mechanisms underlying the metabolic disturbances, the pathophysiology and the clinical phenotype of the disease.

STUDY ON ASSOCIATION OF SERUM FERRITIN &amp; SERUM CERULOPLASMIN IN PREGNANCY: A CASE CONTROL STUDY

Objectives – To compare the levels of serum ferritin &amp; serum ceruloplasmin in pregnant &amp; non- pregnant women &amp; to nd out whether any correlation exists between ferritin &amp; ceruloplasmin levels in pregnancy. Methods –Case population comprised of pregnant women coming for routine antenatal visit in OPD, Nil Ratan Sirkar Medical College &amp; Hospital rd in their 3 trimester of pregnancy. Patient of pre-existing iron deciency anaemia, pregnancy induced hypertension, hypothyroidism, diabetes mellitus, hemoglobinopathies like sickle cell anaemia, thalassemia, were excluded from our study. A control group of healthy, non-pregnant subjects was used for comparison. Results – Serum ferritin level was found to be lower in pregnancy than in non-pregnant women. However the decrease was not found to be statistically signicant. Serum ceruloplasmin was found to be higher in pregnant than in non pregnant women &amp; this increase was found to be statistically signicant. Statistically signicant negative correlation was also been found between serum ferritin &amp; serum ceruloplasmin. Conclusion - Our study establishes the fact that there is increase in serum ceruloplasmin concentration in pregnancy &amp; this increase is further accelerated in iron decient state designated by decreased serum ferritin concentration.

Особливості клінічного перебігу хвороби Вільсона в дітей

Purpose — to discover peculiarities of Wilson disease course in children dependently on the variant of liver affection. Materials and methods. Anamnesis of the disease and clinical and paraclinical peculiarities of the course of the disease with consideration of liver affection severity have been studied in 50 children aged 5–17 years. Results. It was estimated that in 52% of children the disease had a form of chronic hepatitis with minimal clinical symptoms, 44% of patients had liver cirrhosis with predominant signs of edematous and ascitic syndrome and 4% had fulminant hepatitis in a debut of the disease. Complicated family anamnesis was detected in 4% of patients. Syndrome of cytolysis predominated in patients with liver damage in the form of chronic hepatitis (р&lt;0.05). Typical biochemical changes in cirrhotic patients were hepatocellular insufficiency with hypoalbuminemia and coagulopathy, hyperbilirubinemia and minimal hypertransaminasemia (р&lt;0.05). Children with cirrhosis in contrast to patients with chronic hepatitis had reliably lower serum ceruloplasmin concentration and reliably higher excretion of copper with urine. Specific for Wilson disease Kayser—Fleischer rings were found out in 36% of patients only. Conclusions. Wilson's disease in children is characterized by progressing course in the form of either chronic hepatitis or liver cirrhosis or, rarely, fulminant hepatitis. Clinical and paraclinical symptoms of the disease are estimated by the severity of liver affection and vary from a course with minimal symptoms in patients with chronic hepatitis to edematous and ascitic syndrome and hepatocellular insufficiency in patients with cirrhosis and fulminant hepatitis. The research was carried out in accordance with the principles of the Helsinki declaration. The study protocol was approved by the Local Ethics Committee of all participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: Wilson's disease, children, chronic hepatitis, liver cirrhosis, course of the disease.