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Sample records for nephrotic syndrome cns

  1. Nephrotic Syndrome

    Science.gov (United States)

    ... your blood — typically with an artificial kidney machine (dialyzer). Chronic kidney disease. Nephrotic syndrome may cause your ... opportunities Reprint Permissions A single copy of these materials may be reprinted for noncommercial personal use only. " ...

  2. Congenital nephrotic syndrome

    Directory of Open Access Journals (Sweden)

    Claudia Fanni

    2014-06-01

    Full Text Available CNS (Congenital nephrotic syndrome is a disorder characterized by the presence of a nephrotic syndrome in the first three months of life. Different pathologies can cause this syndrome. In general, we can distinguish primary forms (sporadic and hereditary and secondary forms (acquired and associated with other syndromes. The most common form is the Finnish CNS (CNF, congenital nephrotic syndrome of the Finnish type, a hereditary form whose name derives from the fact that the highest incidence is described in that country (1.2:10,000. The pathogenesis, the clinical picture, the diagnostic criteria, the therapy and the outcome are described in details.  Proceedings of the International Course on Perinatal Pathology (part of the 10th International Workshop on Neonatology · October 22nd-25th, 2014 · Cagliari (Italy · October 25th, 2014 · The role of the clinical pathological dialogue in problem solving Guest Editors: Gavino Faa, Vassilios Fanos, Peter Van Eyken

  3. Congenital nephrotic syndrome.

    Science.gov (United States)

    Hamed, Radi Ma

    2003-01-01

    The congenital nephrotic syndrome (CNS) is an uncommon disorder with onset of the nephrotic syndrome usually in the first three months of life. Several different diseases may cause the syndrome. These may be inherited, sporadic, acquired or part of a general malformation syndrome. The clinical course is marked by failure to thrive, recurrent life threatening bacterial infections, and early death from sepsis and/or uremia. A characteristic phenotype may be seen in children with CNS. The majority of reported cases of CNS are of the Finnish type (CNF). Although the role of the glomerular basement membrane has been emphasized as the barrier for retaining plasma proteins, recent studies have clearly shown that the slit diaphragm is the structure most likely to be the barrier in the glomerular capillary wall. The gene (NPHS1) was shown to encode a novel protein that was termed nephrin, due to its specific location in the kidney filter barrier, where it seems to form a highly organized filter structure. Nephrin is a transmembrane protein that probably forms the main building block of an isoporous zipper-like slit diaphragm filter structure. Defects in nephrin lead to the abnormal or absent slit diaphragm resulting in massive proteinuria and renal failure.

  4. Radiation nephritis causing nephrotic syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Jennette, J.C.; Ordonez, N.G.

    1983-12-01

    Clinical symptoms of acute radiation nephritis with nephrotic syndrome developed in a fifty-six-year-old woman after abdominal radiation therapy for an astrocytoma of the spinal cord. The diagnosis of radiation nephritis was confirmed by renal biopsy. To our knowledge, this is the first documented case of radiation nephritis associated with nephrotic syndrome.

  5. Nephrotic syndrome associated with meningioma

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    P P Zachariah

    2013-01-01

    Full Text Available A 58-year-old man presented with recurrent frontal meningioma and nephrotic syndrome. Renal biopsy could not be done in view of the rapid neurological deterioration. The patient underwent surgical resection of the tumor. Within 4 weeks, the edema decreased, serum albumin improved, and proteinuria decreased spontaneously. At three months of followup, the patient had attained complete remission of nephrotic state.

  6. Latest research progress on acute nephrotic syndrome

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    Satinder Kakar

    2017-01-01

    Full Text Available Etiology of nephrotic syndrome is somewhat complex in nature. It may range from primary to secondary forms. Nephrotic syndrome patients often need immunosuppressive treatment although it has some side effects and may lead to renal disease which may be acute or severe. This review deals with herbal treatment and other recent approaches for treating symptoms of nephrotic syndrome.

  7. NEPHROTIC SYNDROME steroid sensitive renal condition

    African Journals Online (AJOL)

    Nephrotic syndrome is primarily a paediatric disorder and is 15 times more common in children than adults. The incidence is 2–3/100,000 children per year, and the majority of affected children will have steroid- sensitive minimal change disease. The characteristic features of nephrotic syndrome are heavy proteinuria.

  8. Genetic Aspects of Nephrotic Syndrome

    DEFF Research Database (Denmark)

    Joshi, Shivani

    Nephrotic syndrome (NS) is characterized by severe proteinuria, hypoalbuminemia, and edema. Depending on response to steroid treatment, patients either have steroid sensitive NS (SSNS) or steroid resistant NS (SRNS). Patients with SRNS often have a poor renal prognosis, focal segmental glomerulos......Nephrotic syndrome (NS) is characterized by severe proteinuria, hypoalbuminemia, and edema. Depending on response to steroid treatment, patients either have steroid sensitive NS (SSNS) or steroid resistant NS (SRNS). Patients with SRNS often have a poor renal prognosis, focal segmental...... steroid dependence or become frequent relapsers. Repeated courses of corticosteroid treatment often cause significant associated morbidity. Familial occurrence of SSNS is rare and suggests a potential genetic origin. However, very little data on molecular genetics of familial SSNS is available...... SSNS. Study I is the first study to describe the genetic findings in 39 patients with sporadic FSGS and/or SRNS, in a highly selected Danish population. We developed a screening tool (high resolution melting analysis) to search for variants in NPHS1, NPHS2, and INF2 genes. This method was shown...

  9. Nephrotic syndrome and Obstetric anesthesia

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    Vijay Kumar Nagpal

    2017-01-01

    Full Text Available Renal disorders in pregnancy can be both difficult to diagnose and manage. They are associated with poor maternal and/or fetal outcomes. In pregnancy, proteinuria is common and can range from mild urinary protein elevations to nephrotic levels. The diagnosis of nephrotic syndrome (NS can be challenging, especially in pregnancy as it can be confused with preeclampsia. NS has an incidence of 0.012%–0.025% in pregnant women. It is diagnosed by the presence of more than 3 g/day of proteins in urine, serum albumin <30 g/dL, generalized edema, hypercholesterolemia, and lipiduria. Proteinuria with hypertension is characterized by the presence of hematuria, red cell casts, raised serum creatinine, and features suggestive of systemic disease. Other causes of proteinuria include preeclampsia, diabetes mellitus (Type 1 and Type 2, Immunoglobulin A nephropathy (Ig A glomerulonephritis, focal and segmental glomerulosclerosis, and lupus nephritis. The maternal risks of NS include acute kidney insult, chronic renal failure, gestational hypertension, preeclampsia, and complications due to hypoalbuminemia. Fetal considerations in NS include fetal growth retardation, prematurity, stillbirth, fetal anasarca, and polyhydramnios. Preconception counseling and immunosuppressive drug therapy can improve overall fetomaternal outcome. We hereby present a unique case of successful anesthetic management of NS in a parturient along with concurrent hypothyroidism and hypertension, for elective cesarean section.

  10. An unusual case of nephrotic syndrome

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    M Sahay

    2016-01-01

    Full Text Available Nephrotic syndrome can be rarely due to inherited disorders of enzymes. One such variety is lecithin cholesterol acyltransferase deficiency. It leads to accumulation of unesterified cholesterol in the eye and other organs. We report a case of nephrotic syndrome with cloudy cornea and hypocholesterolemia with foam cells and lipid deposits on renal biopsy. Awareness about this rare disease may help in the early institution of specific measures to prevent progression to end-stage renal disease.

  11. Rituximab for nephrotic syndrome in children.

    Science.gov (United States)

    Iijima, Kazumoto; Sako, Mayumi; Nozu, Kandai

    2017-04-01

    Idiopathic nephrotic syndrome is the most common chronic glomerular disease in children. At least 20 % of children with this syndrome show frequent relapses and/or steroid dependence during or after immunosuppressive therapies, a condition defined as complicated frequently relapsing/steroid-dependent nephrotic syndrome (FRNS/SDNS). Approximately 1-3 % of children with idiopathic nephrotic syndrome are resistant to steroids and all immunosuppressive agents, a condition defined as refractory steroid-resistant nephrotic syndrome (SRNS); these SRNS children have a high risk of end-stage renal failure. Rituximab, a chimeric anti-CD20 monoclonal antibody, has been shown to be effective for patients with complicated FRNS/SDNS and refractory SRNS. This review describes the recent results of rituximab treatment applied to pediatric nephrotic syndrome, as well as those of our recent study, a multicenter, double-blind, randomized, placebo-controlled trial of rituximab for childhood-onset complicated FRNS/SDNS (RCRNS01). The overall efficacy and safety of rituximab for this disease are discussed.

  12. Rare case of nephrotic syndrome: Schimke syndrome.

    Science.gov (United States)

    Pedrosa, Anna Kelly Krislane de Vasconcelos; Torres, Luiz Fernando Oliveira; Silva, Ana Corina Brainer Amorim da; Dantas, Adrianna Barros Leal; Zuntini, Káthia Liliane da Cunha Ribeiro; Aguiar, Lia Cordeiro Bastos

    2016-01-01

    Schimke syndrome corresponds to dysplasia of bone and immunity, associated with progressive renal disease secondary to nephrotic syndrome cortico-resistant, with possible other abnormalities such as hypothyroidism and blond marrow aplasia. It is a rare genetic disorder, with few reports in the literature. The most frequent renal involvement is nephrotic syndrome with focal segmental glomerulosclerosis and progressive renal failure. The objective of this study was to report a case of Schimke syndrome, diagnostic investigation and management of the case. Resumo A síndrome Schimke corresponde à displasia imuno-óssea, associada à doença renal progressiva secundária à síndrome nefrótica córtico-resistente, podendo haver outras anormalidades como hipotireoidismo e aplasia de medula óssea. Trata-se de uma patologia genética rara, com poucos relatos na literatura. O acometimento renal mais frequente é uma síndrome nefrótica por glomeruloesclerose segmentar e focal e falência renal progressiva. O objetivo deste estudo foi relatar um caso de síndrome de Schimke, investigação diagnóstica e condução do caso.

  13. Dyslipidaemia in nephrotic syndrome: mechanisms and treatment

    Science.gov (United States)

    Agrawal, Shipra; Zaritsky, Joshua J.; Fornoni, Alessia; Smoyer, William E.

    2018-01-01

    Nephrotic syndrome is a highly prevalent disease that is associated with high morbidity despite notable advances in its treatment. Many of the complications of nephrotic syndrome, including the increased risk of atherosclerosis and thromboembolism, can be linked to dysregulated lipid metabolism and dyslipidaemia. These abnormalities include elevated plasma levels of cholesterol, triglycerides and the apolipoprotein B containing lipoproteins VLDL and IDL; decreased lipoprotein lipase activity in the endothelium, muscle and adipose tissues; decreased hepatic lipase activity; and increased levels of the enzyme PCSK9. In addition, there is an increase in the plasma levels of immature HDL particles and reduced cholesterol efflux. Studies from the past few years have markedly improved our understanding of the molecular pathogenesis of nephrotic syndrome associated dyslipidaemia, and also heightened our awareness of the associated exacerbated risks of cardiovascular complications, progressive kidney disease and thromboembolism. Despite the absence of clear guidelines regarding treatment, various strategies are being increasingly utilized, including statins, bile acid sequestrants, fibrates, nicotinic acid and ezetimibe, as well as lipid apheresis, which seem to also induce partial or complete clinical remission of nephrotic syndrome in a substantial percentage of patients. Future potential treatments will likely also include inhibition of PCSK9 using recently developed anti PCSK9 monoclonal antibodies and small inhibitory RNAs, as well as targeting newly identified molecular regulators of lipid metabolism that are dysregulated in nephrotic syndrome. PMID:29176657

  14. AKI in Children Hospitalized with Nephrotic Syndrome.

    Science.gov (United States)

    Rheault, Michelle N; Zhang, Lei; Selewski, David T; Kallash, Mahmoud; Tran, Cheryl L; Seamon, Meredith; Katsoufis, Chryso; Ashoor, Isa; Hernandez, Joel; Supe-Markovina, Katarina; D'Alessandri-Silva, Cynthia; DeJesus-Gonzalez, Nilka; Vasylyeva, Tetyana L; Formeck, Cassandra; Woll, Christopher; Gbadegesin, Rasheed; Geier, Pavel; Devarajan, Prasad; Carpenter, Shannon L; Kerlin, Bryce A; Smoyer, William E

    2015-12-07

    Children with nephrotic syndrome can develop life-threatening complications, including infection and thrombosis. While AKI is associated with adverse outcomes in hospitalized children, little is known about the epidemiology of AKI in children with nephrotic syndrome. The main objectives of this study were to determine the incidence, epidemiology, and hospital outcomes associated with AKI in a modern cohort of children hospitalized with nephrotic syndrome. Records of children with nephrotic syndrome admitted to 17 pediatric nephrology centers across North America from 2010 to 2012 were reviewed. AKI was classified using the pediatric RIFLE definition. AKI occurred in 58.6% of 336 children and 50.9% of 615 hospitalizations (27.3% in stage R, 17.2% in stage I, and 6.3% in stage F). After adjustment for race, sex, age at admission, and clinical diagnosis, infection (odds ratio, 2.24; 95% confidence interval, 1.37 to 3.65; P=0.001), nephrotoxic medication exposure (odds ratio, 1.35; 95% confidence interval, 1.11 to 1.64; P=0.002), days of nephrotoxic medication exposure (odds ratio, 1.10; 95% confidence interval, 1.05 to 1.15; Pchildren with nephrotic syndrome. Nephrotoxic medication exposure was common in this population, and each additional nephrotoxic medication received during a hospitalization was associated with 38% higher risk of AKI. AKI was associated with longer hospital stay after adjustment for race, sex, age at admission, clinical diagnosis, and infection (difference, 0.45 [log]days; 95% confidence interval, 0.36 to 0.53 [log]days; Pchildren hospitalized with nephrotic syndrome and should be deemed the third major complication of nephrotic syndrome in children in addition to infection and venous thromboembolism. Risk factors for AKI include steroid-resistant nephrotic syndrome, infection, and nephrotoxic medication exposure. Children with AKI have longer hospital lengths of stay and increased need for intensive care unit admission. Copyright © 2015 by the

  15. Congenital nephrotic syndrome. Gallium-67 imaging

    International Nuclear Information System (INIS)

    Trepashko, D.W.; Gelfand, M.J.; Pan, C.C.

    1988-01-01

    Congenital nephrotic syndrome is a rare disorder. Heavy proteinuria, hypoalbuminemia, and edema occur during the first 3 months of life. Initial cases were reported from Finland and sporadic cases have occurred elsewhere. Finnish cases demonstrated an autosomal recessive inheritance pattern; currently, Finnish and non-Finnish types are recognized. The clinical course consists of failure to thrive, frequent infections, declining renal function, and early death by age 4 years from sepsis or uremia. Recently renal transplantation has improved the prognosis of patients with this disease. An abnormal Ga-67 scan in a case of congenital nephrotic syndrome is presented

  16. NEPHROTIC SYNDROME: PAST, PRESENT AND FUTURE

    Directory of Open Access Journals (Sweden)

    M. S. Ignatova

    2017-01-01

    Full Text Available This literature review is focused to change our ideas about the etiology, pathogenesis and treatment tactics of the nephrotic syndrome  in recent decades. The change in the treatment outcomes of the primary nephrotic syndrome in connection with the emergence of new  therapy technologies, is shown. Features of the course, examination and therapy of congenital and infantile nephrotic syndrome and  the possibility of the debut of a nephrotic syndrome associated with various gene mutations and at an older age are presented. Principal differences in diagnostic and therapeutic approaches are accentuated depending on the cause of the development of the disease.  Modern syndromological and pathogenetic methods of therapy of primary nephrotic syndrome are presented, and the immediate opportunities for the introduction of new treatment technologies based on the use of monoclonal antibodies, are shown.

  17. Superior sagittal sinus thrombosis: a rare complication of nephrotic syndrome.

    Directory of Open Access Journals (Sweden)

    Tullu M

    1999-10-01

    Full Text Available A two and half year-old-male child, known case of steroid responsive nephrotic syndrome presented with fever and vomiting of acute onset. He was diagnosed to have superior sagittal sinus thrombosis on a contrast computerised tomographic scan of brain. Recovery was complete without anticoagulant therapy. Superior sagittal sinus thrombosis is an extremely rare complication of nephrotic syndrome.

  18. Treatment of anemia of nephrotic syndrome with recombinant erythropoietin

    NARCIS (Netherlands)

    Gansevoort, RT; Vaziri, ND; deJong, PE

    Nephrotic syndrome has been recently shown to cause erythropoietin (EPO) deficiency in humans and experimental models. However, efficacy and safety of recombinant EPO (rEPO) in the treatment of the associated anemia has not been previously investigated. We report a patient with nephrotic syndrome

  19. Bardet-Biedl syndrome presenting with steroid sensitive nephrotic syndrome

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    K K Singh

    2015-01-01

    Full Text Available Bardet-Biedl syndrome (BBS is a rare autosomal recessive disorder characterized by postaxial polydactyly, retinitis pigmentosa, central obesity, mental retardation, hypogonadism, and renal involvement. Renal involvement in various forms has been seen in BBS. Cases with nephrotic range proteinuria not responding to steroid have been described in this syndrome. Here we report a case of BBS who presented with nephrotic range proteinuria. The biopsy findings were suggestive of minimal change disease. The child responded well to steroid therapy and remains in remission.

  20. Circulating dendritic cells in pediatric patients with nephrotic syndrome

    African Journals Online (AJOL)

    EL-HAKIM

    nephrotic syndrome, circulating DCs were measured by flowcytometry. Results: Circulating DC count ... parents or caregivers of each child before enrollment in the study. ..... role in initiating the primary immune response. On the basis of the ...

  1. Syncope as initial symptom for nephrotic syndrome: a case report

    Science.gov (United States)

    Wu, Xuemei; Wang, Guangliang; Feng, Jiachun

    2015-01-01

    Although syncope and nephrotic syndrome are frequently encountered independently in pediatric practice, syncope as the initial symptom for nephrotic syndrome is rarely observed in the pediatric age group. In this report, we present the case of 3-year-old boy with nephrotic syndrome who presented with a history of three episodes of syncope before admission. The syncope occurred after excessive fluid loss or inadequate intake of fluids and was relieved spontaneously. History taking revealed that the early morning palpebral edema, and laboratory tests showed decreased plasma protein levels and elevated serum lipid levels. Nephrotic syndrome was diagnosed, but could not be confirmed histopathologically because the patient’s parent refused consent for biopsy. The patient was managed with fluid expansion, correction of acidosis, and improvement of microcirculation to prevent recurrence of syncope, and glucocorticoids were administered to prevent disease progression. PMID:26629237

  2. Renal Doppler Indices in Children with Nephrotic Syndrome ...

    African Journals Online (AJOL)

    olayemitoyin

    in proteinuric conditions like Paediatric Nephrotic syndrome (NS) which is a glomerular disease. ... the mean RI and PI of the NS cases and controls, except in the left middle .... predominantly either overweight or obese, when ... Weight (Kg).

  3. Mesothelioma of the testis and nephrotic syndrome: a case report

    Directory of Open Access Journals (Sweden)

    Bacchetta Justine

    2009-06-01

    Full Text Available Abstract Introduction Paraneoplastic glomerulopathies are rare manifestations of neoplastic disease to be distinguished from iatrogenic renal damage. Solid tumors are preferentially associated with membranous nephropathy, whereas Hodgkin's lymphomas are associated with minimal change disease. Case presentation We report a 63-year-old Caucasian male diagnosed with a mesothelioma of the tunica vaginalis testis who, secondary to this, also presented with a nephrotic syndrome due to minimal change disease. In the present case, the paraneoplastic etiology of the nephrotic syndrome can be discussed on four unusual elements: minimal change lesions were found; the glomerulopathy was very sensitive to corticosteroids; the nephrotic syndrome occurred 11 months after the diagnosis of the primary malignancy, but concomitantly with the recurrence; and the nephrotic syndrome did not decrease with tumor control and did not recur when the mesothelioma escaped treatment. No other etiologies could nevertheless explain this phenomenon. Conclusion Paraneoplastic nephrotic syndrome is often associated with membranous nephropathy in patients with solid tumors, especially in patients with lung and gastrointestinal tract neoplasia. The management of these patients is associated with a symptomatic treatment such as sodium and water restriction, diuretics and ACE inhibitors and a prophylaxis of specific complications of nephrotic syndrome including thromboembolism, infections and lipid abnormalities. Treatment of neoplasia must be undertaken rapidly, treatments must be regularly analyzed and drugs binding to albumin may be used with precaution.

  4. Management of idiopathic nephrotic syndrome in childhood

    Directory of Open Access Journals (Sweden)

    Peco-Antić Amira

    2004-01-01

    Full Text Available The management of idiopathic nephrotic syndrome (INS in children includes immunosuppressive and symptomatic treatment. The response to corticosteroid therapy is the best prognostic marker of the disease. The majority of children with INS (about 85% are steroid-sensitive as they normalize proteinuria within 4 weeks of daily, oral prednisone administration. The most of steroid-sensitive patients (94% has minimal change of nephrotic syndrome, while the majority (80.5%-94.4% of those who are steroid-resistant has focal segmental glomerulosderosis or mesangioproliferative glomerulonephritis. Initial therapy of INS consists of 60 mg/m2/day prednisone daily for 4 weeks followed by 40 mg/m2 on alternate days for 4 weeks, thereafter decreasing alternate day therapy every month by 25% over the next 4 months. Thus, the overall duration of the initial cortico-steroids course is 6 months that may be significantly protective against the future development of frequent relapses. Approximately 30% of patients experience only one attack and are cured after the first course of therapy; 10-20% have only 3 or 4 steroid-responsive episodes before permanent cure; the remaining 40-50% of patients are frequent relapsers, or steroid-dependent. Standard relapse therapy consists of 60 mg/m2/ day prednisone until urine is protein free for at least 3 days, followed by 40 mg/m2 on alternate days for 4 weeks. The treatment of frequent-relapses and steroid-dependent INS includes several different regimens: maintenance (6 months alternate steroid therapy just above steroid threshold (0.1-0.5 mg/kg/ 48h, levamisole, alkylating agents (cyclophosphamide or chlorambucil or cyclosporine. The worse prognosis is expected in steroid-resistant patients who are the most difficult to treat. Renal biopsy should be performed in them. At present, there is no consensus on therapeutic regimen for steroid-resistant patients. The following immunosuppressive drugs have been used with varying

  5. Cerebral venous thrombosis and secondary polycythemia in a case of nephrotic syndrome.

    Science.gov (United States)

    Nagaraju, Shankar Prasad; Bairy, Manohar; Attur, Ravindra Prabhu; Sambhaji, Charudutt Jayant

    2016-03-01

    Cerebral venous thrombosis (CVT) and polycythemia are considered as rare and life threatening complications of nephrotic syndrome. We report an unusual combination of both these complications in a case of nephrotic syndrome due to minimal change disease that was treated successfully. There was prompt and complete remission of nephrotic syndrome with steroid therapy, concurrent with complete resolution of polycythemia and CVT.

  6. Cerebral venous thrombosis and secondary polycythemia in a case of nephrotic syndrome

    Directory of Open Access Journals (Sweden)

    Shankar Prasad Nagaraju

    2016-01-01

    Full Text Available Cerebral venous thrombosis (CVT and polycythemia are considered as rare and life threatening complications of nephrotic syndrome. We report an unusual combination of both these complications in a case of nephrotic syndrome due to minimal change disease that was treated successfully. There was prompt and complete remission of nephrotic syndrome with steroid therapy, concurrent with complete resolution of polycythemia and CVT.

  7. Histopathological types in adult nephrotic syndrome

    Directory of Open Access Journals (Sweden)

    Md. Ghulam Yusuf

    2016-01-01

    Full Text Available In Bangladesh, there are very few studies about biopsy proven adult Nephrotic syndrome (NS with histological types and their clinical findings. To determine the histological types of glomerulonephritis (GN in adult NS and correlate them with the clinical presentations and biochemical parameters, we studied 100 biopsies in 87 patients who underwent ultrasonography- guided renal biopsy in Rangpur Medical College and Hospital from July 2010 to June 2012. The mean age of the patients was 32.8 ± 13.2 years; male was preponderance (72.4% and most of the patients (67.8% came from rural areas. Membranoproliferative GN (MPGN was the most common underlying cause that was found in 32 (36.8% patients followed by mesangial prolife- rative GN in 27 (31% patients, membranous GN in 16 (18.4% cases, minimal change disease in four (4.6% patients, diffuse proliferative GN in four (4.6% patients, focal segmental GN, and focal proliferative GN in two (2.4% patients each. High proteinuria level was found in minimal change disease, which was 7.59 ± 0.24 g/24 h (mean ± standard deviation. The most common symptoms were oliguria (92% and edema (86.2% followed by hematuria (dark urine (72.4% and hypertension (35.6%. MPGN was the most common histological type of adult NS in Rangpur.

  8. Childhood Nephrotic Syndrome in Aminu Kano Teaching Hospital ...

    African Journals Online (AJOL)

    Methods: A prospective study spanning two years (July 2002 – August 2004). Twenty two children with nephrotic syndrome were seen ate the Aminu Kano Teaching Hospital, Kano. The demographic, clinical and laboratory features and response to treatment were documented. Results: Nephritic syndrome made up of 1.2% ...

  9. BILATERAL SEROUS MACULAR DETACHMENT IN A PATIENT WITH NEPHROTIC SYNDROME.

    Science.gov (United States)

    Bilge, Ayse D; Yaylali, Sevil A; Yavuz, Sara; Simsek, İlke B

    2018-01-01

    The purpose of this study was to report a case of a woman with nephrotic syndrome who presented with blurred vision because of bilateral serous macular detachment. Case report and literature review. A 55-year-old woman with a history of essential hypertension, diabetes, and nephrotic syndrome was presented with blurred vision in both eyes. Her fluorescein angiography revealed dye leakage in the early and subretinal pooling in the late phases, and optical coherence tomography scans confirmed the presence of subretinal fluid in the subfovel area. In nephrotic syndrome cases especially with accompaniment of high blood pressure, fluid accumulation in the retina layer may occur. Serous macular detachment must be kept in mind when treating these patients.

  10. Nephrotic Syndrome in a Child Suffering from Tetralogy of Fallot: A Rare Association

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    Pépé Mfutu Ekulu

    2015-01-01

    Full Text Available Nephrotic syndrome is an uncommon complication of tetralogy of Fallot and has been rarely reported in pediatric population. We describe a 4-year-old female Congolese child who was referred for investigation for persistent dyspnea, edema, and cyanosis and nephrotic range proteinuria. Our patient presented with a tetralogy of Fallot and nephrotic syndrome. Conclusion. This case reminds us that children with tetralogy of Fallot may develop nephrotic proteinuria.

  11. Recent Treatment Advances and New Trials in Adult Nephrotic Syndrome

    Directory of Open Access Journals (Sweden)

    Eva Königshausen

    2017-01-01

    Full Text Available The etiology of nephrotic syndrome is complex and ranges from primary glomerulonephritis to secondary forms. Patients with nephrotic syndrome often need immunosuppressive treatment with its side effects and may progress to end stage renal disease. This review focuses on recent advances in the treatment of primary causes of nephrotic syndrome (idiopathic membranous nephropathy (iMN, minimal change disease (MCD, and focal segmental glomerulosclerosis (FSGS since the publication of the KDIGO guidelines in 2012. Current treatment recommendations are mostly based on randomized controlled trials (RCTs in children, small RCTs, or case series in adults. Recently, only a few new RCTs have been published, such as the Gemritux trial evaluating rituximab treatment versus supportive antiproteinuric and antihypertensive therapy in iMN. Many RCTs are ongoing for iMN, MCD, and FSGS that will provide further information on the effectiveness of different treatment options for the causative disease. In addition to reviewing recent clinical studies, we provide insight into potential new targets for the treatment of nephrotic syndrome from recent basic science publications.

  12. [Relationship between hyperuricemia and primary nephrotic syndrome in children].

    Science.gov (United States)

    Xiao, Huijie; Li, Qian; Wang, Fang; Yao, Yong; Zhong, Xuhui

    2014-11-01

    To analyze the relationship between hyperuricemia and primary nephrotic syndrome in childhood. A retrospective study was carried out in 107 children with primary nephrotic syndrome. The clinical data were analyzed with statistical methods to identify the related factors with hyperuricemia. The morbidity of hyperuricemia in children with primary nephrotic syndrome was 45% (48/107). Compared to those in normal serum uric acid group, the incidence of hypertension (33%, 16/48), serum triglyceride [2.59(1.62-3.87) mmol/L], creatinine [43.85(33.38-56.38)mmol/L], urea [6.11(3.77-8.40)mmol/L] and blood uric acid/creatinine ratio [9.30(7.03-12.72)] increased while creatinine clearance rate [141.74(103.57-160.97)ml/(min·1.73 (2))] decreased in hyperuricemia group. Hyperuricemia in children with primary nephrotic syndrome correlated with the increase of serum creatinine, urea and blood uric acid/creatinine ratio, the decrease of creatinine clearance rate and the occurance of hypertension.

  13. Renal Doppler Indices in Children with Nephrotic Syndrome ...

    African Journals Online (AJOL)

    Summary: The resistive and pulsatility indices are known tools for assessing renal function in kidney diseases, especially in proteinuric conditions like Paediatric Nephrotic syndrome (NS) which is a glomerular disease. However, there is a limited knowledge in the use of Doppler Resistive and pulsatility indices in the ...

  14. The management of nephrotic syndrome in children | Hodson ...

    African Journals Online (AJOL)

    Data from RCTs supports the use of alkylating agents (cyclophosphamide, chlorambucil), cyclosporin and levamisole in these children to achieve prolonged periods of remission after induction of remission with prednisone. Steroid resistant nephrotic syndrome is more common in Africa. Few therapies are effective. In such ...

  15. Nephrotic syndrome among children in Kano: A clinicopathological ...

    African Journals Online (AJOL)

    2013-11-14

    Nov 14, 2013 ... generally has a favorable response to glucocorticoid therapy in over 80% of patients.[6‑9] Children having steroid‑resistant nephrotic syndrome (SRNS) with focal and segmental glomerular sclerosis (FSGS) or MCNS run a high risk of resistance to immunosuppressive therapy.[10] The incidence of FSGS ...

  16. CASE REPORT Thirty years old lady with nephrotic syndrome: a ...

    African Journals Online (AJOL)

    CASE REPORT. Thirty years old lady with nephrotic syndrome: a case of biopsy proven lupus nephritis in Tanzania. FRANCIS FREDRICK1,2*, PASCHAL J. RUGGAJO2,3,GYAVIIRA MAKANGA3, CHARLES K. SHIJA3, MIKAEL. AMDEMARIAM3, BELSON RUGWIZAGONGA4 and JAMES N. KITINYA4. 1Department of ...

  17. RENIN ANGIOTENSIN SYSTEM GENE POLYMORPHISMS IN CHILDREN WITH NEPHROTIC SYNDROM

    Directory of Open Access Journals (Sweden)

    Zh.P. Sharnova

    2006-01-01

    Full Text Available To investigate the role of the reninangiotensin system genes polymorphisms in develop and progression of nephrotic syndrom (NS in children we determined the genotypes of angiotensin converting enzyme (ACE, angiotensinogen (AGT and angiotensin ii receptor (ATII-R of 1 type in 80 russian children with ns including and 15 children with chronic renal failure (CRF. Genotype frequencies did not differ between patients with ns and controls (n = 165. The distribution of ace, AGT and ATII-R 1 type genotypes was similar among ns sub groups, such as focal segmental glomerulosclerosis (FSGS (n = 18, steroid-sensitive nephrotic syndrome (n = 32, nephrotic syndrome with hypertension and hemoturia (n = 22 and with control group. When ns subjects with CRF (n = 15 were compared with control, the prevalence of ace DD genotype was significantly higher (47% VS 21%; χ2 = 4,44; p < 0,05. Our results indicate that the DD genotype ace may be a factor of risk for the dеvеlopment of progressive renal impairment in the children with nephrotic syndrome. The analysis of treatment's effect with inhibitor of ace in groups patients with steroid resistant NS (SRNS demonstrated decreasing of renoprotective effect of this drugs in patients with id and dd genotypes com? Pared with ii genotype: the degree of blood pressure, proteinuria and the rate of glomerular filtration decrease was significantly lower (55,46 ± 9,25 VS 92,74 ± 25; р < 0,05 in these patients.Key words: nephrotic syndrom, chronic renal failure, polymorphism of genes, renin-angiotensin system.

  18. Cyclosporine utilization in Idiopathic Nephrotic Syndrome in children

    International Nuclear Information System (INIS)

    Saeed, B.; Sheriff, S.; Ossman, Mohd Imad

    2006-01-01

    The treatment of steroid-resistant focal segmental glomerulosclerosis (FSGS) imposes one the most perplexing and frustrating problems on nephrologists. Cyclosporine A (CsA) is widely considered as the treatment of choice for steroid-resistant or dependent nephrotic children. We reviewed the clinical outcome in children with idiopathic nephrotic syndrome (INS) under CsA treatment. A total of 22 children presented with either steroid resistant nephrotic syndrome (SRNS) (14 children), or steroid-dependent nephrotic syndrome (SDNS) (8 children) during the period from August 2002 to February 2005; the mean age for both groups was 7.6 years (range: 23 months-15 years). Renal histology showed FSGS in 14 (63%) patients, minimal change disease (MCD) in 4(18%), diffuse mesangial glomerulonphritis (MesGN) in three (13.6%), and membranous glomerulonephritis (MGN) in two (6.8%). Treatment with CsA in combination with alternate-day prednisolone induced remission in 15(68%) patients; 9(60%) patients had complete remission and six (40%) partial remission. Seven (50%) patients in SRNS group responded to CsA treatment; two (14.2%) patients had complete remission and 5 (35.7%) had partial remission. Seven ( 87.5%) children in SDNS group had complete remission and one (13.5%) had partial remission. We conclude that this study demonstrates the efficacy of CsA in inducing remission in the steroid dependent is higher than in the steroid resistant nephrotic children. We believe that CsA is probably a good alternative therapy in this population. (author)

  19. Cellulitis as complication of nephrotic syndrome in a pediatric patient

    Science.gov (United States)

    Siregar, R. S.; Daulay, K. R.; Siregar, B.; Ramayani, O. R.; Eyanoer, P. C.

    2018-03-01

    Nephrotic syndrome is a chronic disease that may act as a risk for other major infection in skin, respiratory and urinary tract, while also increasingthe chance for other diseases, like peritonitis, meningitis, and cellulitis. Cellulitis is often caused by Streptococcus β-hemolytic, Staphylococcus aureus, and Escherichia coli. The clinical features of cellulitis marked with redness rash and well-defined borders, pain pressure and swelling. Hypoalbuminemia which occurs due to proteinuria occurred in this patient acts as a risk factor for cellulitis. It has been reported the case of cellulitis as one of the complications of the nephrotic syndrome in the pediatric patient. The treatment has been given to the patient such as antibiotics and supportive therapy and also planned albumin substitution.

  20. Histopathological diagnosis and outcome of paediatric nephrotic syndrome

    International Nuclear Information System (INIS)

    Ejaz, I; Khan, H.I.; Javaid, B.K.; Bhatti, M.T.; Rasool, G.

    2004-01-01

    Objective: To determine the histological picture and outcome of treatment in cases of childhood nephrotic syndrome who needed renal biopsy. Subjects and Methods: Children suffering from nephrotic syndrome who had atypical features at presentation were initially or late non-responders; frequent relapsers on > 1 mg kg/day and were steroid dependent or frequently relapsed on < 1 mg kg/day but developed steroid toxicity were included. Renal biopsy was performed in these patients. Treatment was administered according to the histopathology reports. Prednisolone 60 mg /m/sup 2//day followed after response by 40 mg /m/sup /2 on alternate days (AD) which was later tapered off. In minimal change nephrotic syndrome (MCNS) with frequent relapses cyclophosphamide, cyclosporine and levimisole were used. For steroid resistant focal segmental glomerulosclerosis (FSGS) intravenous pulses of methylprednisolone and cyclosporine were also given. These patients were followed to see the response of the therapy. Results: The commonest diagnosis was focal segmental glomerulosclerosis (FSGS) (42%) followed by minimal change disease (MCNS) (22%), membranoproliferative or mesangiocapillary glomerulonephritis (MPGN) (14%) and Mesangioproliferative glomerulonephritis (Mes PGN) (12%). There were 6% cases of membranous nephropathy and 4% of diffuse proliferative glomerulonephritis. On presentation, 40% had hematuria, 20% were found to be hypertensive, 12% patients had renal insufficiency and in 40% C3 level was low. Majority of the patients with MPGN and FSGS had atypical features whereas none of the patients with membranous nephropathy had any of these features. Thirty percent cases each of FSGS and MCNS were responders. Among non-responders there were 4 cases of FSGS and one of MPGN. Conclusion: FSGS was the commonest histology in cases of childhood nephrotic syndrome that needed renal biopsy. Highest frequency of atypical features was seen in MPGN and FSGS. (author)

  1. CLINICO PATHOLOGICAL STUDY OF NEPHROTIC SYNDROME IN ADULTS

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    Deepa

    2015-11-01

    Full Text Available CONTEXT: Etiology of nephrotic syndrome (NS in adults varies depending on the geographical location and is poorly studied in the Indian subcontinent. AIMS: To study the clinical features, biochemical profile and histopathological pattern of various types of glomerulonephritis in adult patients with nephrotic syndrome. METHODS AND MATERIAL: Patients (≥15 years old with nephrotic syndrome presenting to our center and undergoing a kidney biopsy from May 2009 to August 2011 were included for this study. All biopsies were subjected to light microscopy.The histopathological spectrum was analyzed according to the various clinical parameters. STATISTICAL ANALYSIS USED: Analysis was performed using SPSS software version 19.Measures obtained included percentages,medians,correlation coefficients and chi square tests. RESULTS: A total of 50 kidney biopsies were included in analysis. Twenty six(52% patients were male and twenty four(48% patients were female. The average age at presentation was 15-24 years. Among the patients, 22(44% were diagnosed with primary glomerular diseases (PGD and 4(8% with secondary glomerular diseases (SGD. The most common histological lesions was membranous nephropathy(24.4% followed by minimal change disease (MCD (17% and membranous nephropathy (MN (17%. The most common form of SGD was lupus nephritis (LN (10%. Membranous nephropathy and focal segmental glomerulosclerosis were the commonest lesions in males.Among females,membranous nephropathy was the commonest. 31(62% patients were in the age group of 15-34 yrs, 17(34% were in the age group 34- 54yrs and only 2(4% were aged above 55yrs. Among the patients, 6(12% had serum creatinine ≥1.5 mg/dL and 12(24% had either macroscopic or microscopic hematuria. CONCLUSIONS: Membranous nephropathy is still the commonest type of nephrotic syndrome in adults followed closely by focal segmental glomerulosclerosis and minimal change disease as per this study.

  2. A Study of Hypoalbuminemia and Pleural Effusionin Pediatric Nephrotic Syndrome

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    Tovan Perinandika

    2017-06-01

    Full Text Available Background: Nephrotic syndrome (NS is a kidney disease that is most often found in children. Hypoalbuminemia in NS can cause a decrease in oncotic pressure causing extravasation of fluid into the interstitial space. In conditions of severe hypoalbuminemia, fluid extravasation may cause occurrence of pleural effusion. The objectives of this study was to analyze the correlation between hypoalbuminemia and pleural effusion in children with NS. Methods: An analytical study was conducted on 69 medical records of pediatric nephrotic syndrome from 1 January 2008–31 December 2013 in dr. Hasan Sadikin General Hospital. Inclusion criteria were pediatric patients between 1-14 years old with NS. Exclusion criteria were patients who already had albumin transfusion, malnutrition, patients with chronic disease, and incomplete medical record information. Contingency coefficient test was carried out to discover the correlation between variables. Results: Out of 89 samples, 69 samples were included. Characteristics of the included patients are male (n=48, female (n=21, age 1–5 (n=24, 6–10 (n=22, 11–14 (n=23, mild hypoalbuminemia (n=3, moderate hypoalbuminemia (n=27, severe hypoalbuminemia (n=39, patients with pleural effusion (n=23, and non-pleural effusion (n=46. There was a significant correlation between  hypoalbuminemia and pleural effusion with p=0.000 (p<0.05 and moderate correlation (r=0.437. Conclusions: Hypoalbuminemia has correlation with pleural effusion in pediatric nephrotic syndrome. Keywords: Hypoalbuminemia, pediatric nephrotic syndrome, pleural effusion DOI: 10.15850/amj.v4n2.1075

  3. Nephrotic syndrome: a rare cause of acute coronary syndrome in a child

    International Nuclear Information System (INIS)

    Khan, J.A.; Shamsi, F.

    2012-01-01

    Patients with nephrotic syndrome are at risk of developing thrombosis in both veins and arteries. Various manifestations in different organs have been reported. Thrombi in heart seen, associated with multi organ thrombosis have been reported on autopsy earlier, but only once in a living patient with nephrotic syndrome. Here, we report a 13 years old boy with steroid-resistant nephrotic syndrome, who developed an asymptomatic but potentially hazardous large intracardiac thrombus. The child developed nephrotic syndrome at the age of 9 years and had multiple recurrences. At the age of 13 years, he developed myocardial infarction (MI) due to embolism from a large intracardiac thrombus. Later on, he was treated with heparin and warfarin anticoagulation. (author)

  4. Nephrotic Syndrome and Acute Renal Failure Apparently Induced by Sunitinib

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    Ying-Shou Chen

    2009-10-01

    Full Text Available We report a case of nephrotic syndrome and acute renal failure apparently induced by sunitinib. A 67-year-old man with a history of metastatic renal cell carcinoma presented with progressive kidney dysfunction with proteinuria, general edema, and body weight gain of 21 kg after undergoing 3 weeks of sunitinib therapy. The patient had taken no other over-the-counter medications, and all other possible causes of nephrotic syndrome were excluded. The Naranjo Adverse Drug Reaction Probability Scale score for this event was 6, indicating a high probability that the observed presentations were associated with use of the drug. However, despite the discontinuation of sunitinib, his condition deteriorated, and hemodialysis was initiated for respiratory distress. A renal biopsy was performed, which revealed ischemic acute tubular necrosis with minimal change nephropathy. In conclusion, nephrologists and oncologists should be aware that nephrotic syndrome with ischemic acute tubular necrosis is a possible adverse effect of sunitinib. For early diagnosis of this condition and to avoid renal damage, we recommend differential diagnosis of serum creatinine and proteinuria in patients undergoing sunitinib therapy.

  5. Seroprotection for hepatitis B in children with nephrotic syndrome.

    Science.gov (United States)

    Mantan, Mukta; Pandharikar, Nagaraj; Yadav, Sangeeta; Chakravarti, Anita; Sethi, Gulshan Rai

    2013-11-01

    Children with nephrotic syndrome have been shown to have lower seroconversion to various vaccines due to immune dysregulation, prolonged immunosuppressive treatment and recurrent prolonged proteinuria.The primary aim of this study was to determine hepatitis B surface antibody (anti-HBs) titers in children with nephrotic syndrome who had been previously vaccinated against hepatitis B. The secondary aim was to study the association of anti-HBs titers with type of disease, schedule and dose of vaccination, and type of immunosuppressive therapy. This cross-sectional study was conducted in the Department of Pediatrics in a tertiary care hospital between January 2011 and January 2012). All children (aged 1-18 years) with nephrotic syndrome who tested negative for hepatitis B surface antigen and who had previously been vaccinated against hepatitis B, with the last dose being at least 1 month prior to being included in the study. A form consisting of history and clinical details was filled in, and the schedule and dose of vaccination(s) received was noted. A blood sample was taken from all patients for biochemical assessment and determination of anti-HBs titer. The patient cohort comprised 75 children (51 males; 24 females) of whom 42 (56%) had steroid-resistant nephrotic syndrome (SRNS) and 33 (44%) had steroid-sensitive nephrotic syndrome (SSNS). Most patients enrolled in the study (96%) were in remission at the time of the biochemical and serological assessment. Twenty-one (28%) patients had received only steroids, while 72 % also received other immunosuppressants. Forty-six (61.3%) patients had received a double dose of vaccine. Of the 75 children enrolled, 36 (48%) and 39 (52%) had an anti-HBs titer of ≥10 mIU/mL (seroprotected) and children with SRNS are less likely to seroconvert with vaccination. A higher dose (double) of hepatitis B vaccine should be used for vaccinating such patients. Anti-HBs titers should be monitored in SRNS patients post-vaccination, and a

  6. Serial Manifestation of Acute Kidney Injury and Nephrotic Syndrome in a Patient with TAFRO syndrome.

    Science.gov (United States)

    Ito, Seigo; Uchida, Takahiro; Itai, Hiroki; Yamashiro, Aoi; Yamagata, Akira; Matsubara, Hidehito; Imakiire, Toshihiko; Shimazaki, Hideyuki; Kumagai, Hiroo; Oshima, Naoki

    2018-06-06

    A 76-year-old woman suddenly developed anasarca and a fever, and an examination revealed thrombocytopenia, reticulin fibrosis, and acute kidney injury, yielding the diagnosis of TAFRO syndrome. Renal replacement therapy and steroid treatment were soon started. Her proteinuria was minor at first; however, once the kidney function improved, nephrotic syndrome occurred. A kidney biopsy showed membranoproliferative glomerulonephritis-like glomerulopathy with massive macrophage infiltration. Although kidney dysfunction is often observed in TAFRO syndrome patients, its detailed mechanism is unclear. This case suggests that TAFRO syndrome involves both acute kidney injury with minor proteinuria and nephrotic syndrome, and these disorders can develop serially in the same patient.

  7. Serum D-dimer concentrations in nephrotic syndrome track with albuminuria, not estimated glomerular filtration rate.

    LENUS (Irish Health Repository)

    Sexton, D J

    2012-01-01

    The nephrotic syndrome is associated with an increased risk of venous and arterial thrombosis. There are little published data on the distribution, interpretation or determinants of serum D-dimer levels in patients with the nephrotic syndrome. We aimed to describe this relationship.

  8. Familial steroid-sensitive idiopathic nephrotic syndrome: seven cases from three families in China

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    Yonghui Xia

    2013-05-01

    Full Text Available OBJECTIVES: Familial steroid-sensitive idiopathic nephrotic syndrome is rare, and only approximately 3% of patients have affected siblings. METHODS: Herein, we report seven cases of patients with steroid-sensitive idiopathic nephrotic syndrome from three Chinese families. Mutational screening of the Nphs2 gene was performed in all the patients. RESULTS: All seven of the familial steroid-sensitive idiopathic nephrotic syndrome cases in our sample exhibited minimal change disease, and one case also presented with mesangial proliferative glomerulonephritis, according to the renal pathology. No significant was associations were found between Nphs2 gene mutations and the onset of proteinuria and nephrotic syndrome in these familial cases. CONCLUSIONS: The presence of minimal change disease is important, but it is not an unusual finding in patients with familial steroid-sensitive idiopathic nephrotic syndrome, which appears to be clinically benign and genetically distinct from other types of nephrosis.

  9. Risk of Nephrotic Syndrome following Enteroviral Infection in Children: A Nationwide Retrospective Cohort Study.

    Science.gov (United States)

    Lin, Jiun-Nong; Lin, Cheng-Li; Yang, Chi-Hui; Lin, Ming-Chia; Lai, Chung-Hsu; Lin, Hsi-Hsun; Kao, Chia-Hung

    2016-01-01

    Nephrotic syndrome is a common chronic illness encountered during childhood. Infections have been identified as a cause of nephrotic syndrome. The aim of this study was to evaluate the association between enteroviral infection and nephrotic syndrome. A nationwide retrospective cohort study was conducted by analyzing data from the National Health Insurance Research Database in Taiwan. Children aged children were randomly selected as the comparison cohort. The primary endpoint was the occurrence of nephrotic syndrome. This study included 280,087 enterovirus-infected children and 280,085 non-enterovirus-infected children. The mean age of the enterovirus-infected children was 2.38 years, and 53.7% of these children were boys. The overall incidence densities of nephrotic syndrome for enterovirus- and non-enterovirus-infected children were 2.65 and 2.21 per 10,000 person-years, respectively. The enterovirus-infected cohort had a higher cumulative incidence of nephrotic syndrome than did the non-enterovirus-infected cohort (log-rank test, p = 0.01). Multivariable analyses revealed that children with enteroviral infection were significantly associated with an increased risk of nephrotic syndrome compared with those without enteroviral infection (adjusted hazard ratio, 1.20; 95% confidence interval, 1.04-1.39; p = 0.01), particularly in children infected with coxsackievirus. Subgroup analyses revealed that enterovirus-infected girls, children of blue-collar workers, and children without allergies had a higher risk of nephrotic syndrome than did children in the non-enterovirus-infected cohort. This study revealed a significant association between enteroviral infection and nephrotic syndrome. Additional studies elucidating the role and pathogenesis of enterovirus in nephrotic syndrome are warranted.

  10. Chronic graft versus host disease and nephrotic syndrome

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    Samia Barbouch

    2014-01-01

    Full Text Available Disturbed kidney function is a common complication after bone marrow transplantation. Recently, attention has been given to immune-mediated glomerular damage related to graft versus host disease (GVHD. We describe a 19-year-old woman who developed membranous glomerulonephritis after bone marrow transplantation (BMT. Six months later, she developed soft palate, skin and liver lesions considered to be chronic GVHD. Fifteen months after undergoing BMT, this patient presented with nephrotic syndrome. A renal biopsy showed mem-branous glomerulonephritis associated with a focal segmental glomerulosclerosis. She was started on corticosteroid treatment with good outcome.

  11. Pulmonary embolism as the primary presenting feature of nephrotic syndrome

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    Pallavi Periwal

    2016-01-01

    Full Text Available A 36-year-old previously healthy male presented with subacute onset of shortness of breath and chest pain. He was diagnosed with bilateral extensive pulmonary embolism (PE. In the absence of any predisposing factors, an extensive workup for unprovoked thrombophilia was done. During the course of his illness, the patient developed anasarca and was diagnosed to be suffering from nephrotic syndrome (NS, secondary to membranous glomerulopathy. Although, thrombotic complications are commonly associated with NS, it is unusual for PE to be the primary presenting feature in these patients.

  12. History of Nephrotic Syndrome and Evolution of its Treatment

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    Abhijeet ePal

    2016-05-01

    Full Text Available The recognition, evaluation, and early treatment of nephrotic syndrome in infants and children originates from physicians dating back to Hippocrates. It took nearly another thousand years before the condition was described for its massive edema requiring treatment with herbs and other remedies. A rich history of observations and interpretations followed over the course of centuries until the recognition of the combination of clinical findings of foamy urine, swelling of the body, and measurements of urinary protein and blood analyses showed the phenotypic characteristics of the syndrome that were eventually linked to the early anatomic descriptions from first kidney autopsies and then renal biopsy analyses. Coincident with these findings were a series of treatment modalities involving the use of natural compounds to a host of immunosuppressive agents that are applied today. With the advent of molecular and precision medicine, the field is poised to make major advances in our understanding and effective treatment of nephrotic syndrome and prevent its long-term sequelae.

  13. A case of Fournier gangrene complicating idiopathic nephrotic syndrome of childhood.

    Science.gov (United States)

    Wright, A J; Lall, A; Gransden, W R; Joyce, M R; Rowsell, A; Clark, G

    1999-11-01

    A 10-year-old boy presenting with steroid resistant nephrotic syndrome developed Fournier gangrene of the scrotum. Antimicrobial drug therapy, intravenous albumin, excision of necrotic scrotum and left orchidectomy followed by skin grafting 3 weeks later led to an excellent cosmetic and medical result. Six months later he remains nephrotic on diuretic and angiotensin converting enzyme inhibitor medication.

  14. Efficacy of levamisole in children with frequently relapsing and steroid-dependent nephrotic syndrome.

    Science.gov (United States)

    Ekambaram, Sudha; Mahalingam, Vijayakumar; Nageswaran, Prahlad; Udani, Amish; Geminiganesan, Sangeetha; Priyadarshini, Shweta

    2014-05-01

    To assess the efficacy of levamisole in frequently relapsing nephrotic syndrome and steroid-dependent nephrotic syndrome. Retrospective analysis of hospital case records. Pediatric nephrology department of a tertiary referral pediatric hospital. 62 children with frequently relapsing nephrotic syndrome and 35 children with steroid-dependent nephrotic syndrome. Case records of children who were diagnosed as steroid-dependant or frequently-relapsing nephrotic syndrome from June 2004 to June 2011, were reviewed. Levamisole was given daily (2 mg/kg/d) along with tapering doses of alternate day steroids after remission on daily steroids. Levamisole was effective in 77.3% children with a better (80.6%) efficacy in frequently relapsing nephrotic syndrome. A total of 34 children completed 1 year follow-up post levamisole therapy. The cumulative mean (SD) steroid dose 1-year before therapy was 4109(1154) mg/m2 and 1-year post therapy was 661 (11) mg/m2 (P<0.001). The relapses were also less during the period of post-levamisole therapy. Levamisole is an effective alternative therapy in frequently relapsing and steroid-dependent nephrotic syndrome.

  15. A histopathological outlook on nephrotic syndrome: A pediatric perspective

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    M K Arif

    2016-01-01

    Full Text Available The developing world is observing changing histopathological patterns of idiopathic nephrotic syndrome (INS. However, the true burden of non-minimal change disease (non-MCD presenting as INS remains unestimated owing to a paucity of data on renal biopsies. Data were collected from January 2006 to June 2014 on 75 children up to 16 years of age who underwent renal biopsies for INS. Mean age at biopsy was 11.2 ± 3.7 years. The male to female ratio was 1.5:1. A total of 25 (33.3% children were steroid sensitive, 36 (48% were steroid resistant, 10 (13.3% were steroid dependent and 4 (5.3% came with relapse of nephrotic syndrome (NS. Focal segmental glomerulosclerosis (FSGS was the most common histopathological subtype observed in 35 (46.8% children followed by membranous glomerulonephritis (MGN in 11 (14.7%, membranoproliferative glomerulonephritis (MPGN and mesangioproliferative glomerulonephritis (MSGN in 4 (5.3% each and IgA nephropathy in one (1.3%. MCD was the histological lesion in 19 (25.3% children. The histopathology established FSGS as the main underlying cause of steroid resistant NS. The study highlights the emergence of non-MCD as the common cause of INS in the pediatric population and signifies the importance of renal biopsies in children with INS.

  16. A STUDY ON OCULAR FINDINGS IN CHILDREN WITH NEPHROTIC SYNDROME

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    Jezeela K

    2018-03-01

    Full Text Available BACKGROUND Nephrotic syndrome occurs when the filtering units of the kidneys- the glomeruli are damaged. The annual incidence of nephrotic syndrome ranges from 2-7 per 100,000 children. Oral corticosteroids form the cornerstone for management of most children with nephrotic syndrome. Long-term steroid therapy in childhood is associated with a number of significant adverse effectsmajor ophthalmic adverse effects include decreased vision, recurrent hordeolum, posterior subcapsular cataract, pseudotumour cerebri, visual hallucinations. This study aims to analyse the ocular findings in children with nephrotic syndrome, and their treatment related ocular abnormalities. MATERIALS AND METHODS This is a cross sectional study, conducted at The Department of Ophthalmology, Government Medical College Thrissur of 1-year duration. Study participants include patients who attended outpatient department of Paediatrics, Govt. Medical College, Thrissur, with clinical and objective investigational evidence of nephrotic syndrome. 70 children who were included in the study were interviewed with a questionnaire; Detailed history was taken from the patients and their parents, regarding the onset of the disease, treatment details, year of starting steroids, history of hypertension, additional drugs, history of defective vision, headache, allergic diseases of eye, eyelid swellings and use of spectacles. Visual acuity was assessed with Snellen s’ chart. Best corrected visual acuity was noted. Acuity was also measured with spectacles if the child was wearing them. Anterior segment was examined under torchlight and later in slit lamp and in all cases fundus examination and retinoscopy were done after dilating pupils with homatropine. Intraocular pressure was measured with Goldman Applanation Tonometer. RESULTS Since the sample size is small, the exact sex distribution cannot be ascertained. History of headache was present in 45 children (64.3%. Visual acuity was assessed

  17. Stem cell mobilization in idiopathic steroid-sensitive nephrotic syndrome.

    Science.gov (United States)

    Lapillonne, Hélène; Leclerc, Annelaure; Ulinski, Tim; Balu, Laurent; Garnier, Arnaud; Dereuddre-Bosquet, Nathalie; Watier, Hervé; Schlageter, Marie-Hélène; Deschênes, Georges

    2008-08-01

    Steroid-sensitive nephrotic syndrome (SSNS) is classically thought to be a T-cell disorder. The aim of this study was to examine whether or not thymus homeostasis was affected in SSNS. Mature and naive T cell recent thymic emigrants were quantified in the peripheral blood of nephrotic patients and controls. Because the generation of new T cells by the thymus ultimately depends on hematopoietic stem cells, CD34+ cells were also included in the study. Nineteen patients with SSNS during relapse, 13 with SSNS during proteinuria remission, and 18 controls were studied. Cell-surface markers (CD3, CD4, CD8, CD19, CD16, CD56, CD45RA, CD62L, CD34, and CD38) were analyzed by flow cytometric analysis. T-cell rearrangement excision circles (TRECs) were quantified in CD2+ cells by real-time polymerase chain reaction. Stroma cell-derived factor-1 (SDF-1) genotype and metalloproteinase-9 (MMP-9) plasma levels were also determined. Mature T cells (CD4+ and CD8+), circulating naive T cells (CD62L+ and CD3+ CD62L+), and recent thymic emigrants (CD45RA+) as well as TRECs, that measure thymus production, had a similar level in the three groups of patients. Conversely, CD34+ hematopoietic stem cells displayed a two-fold increase in SSNS patients during relapse either compared with controls or SSNS patients at remission. In addition, compared with controls, SSNS patients at remission displayed (1) a decrease in CD19+ cells (B cells) and (2) an increase in CD16CD56+ cells [natural killer (NK) cells]. In conclusion, thymus homeostasis is not significantly affected in nephrotic patients. Hematopoietic stem-cell mobilization at proteinuria relapse, as well as changes in B and NK cells during remission, suggest that SSNS might be due to a general disturbance of hematopoietic and immune cell trafficking.

  18. The evidence-based approach to adult-onset idiopathic nephrotic syndrome

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    Pietro A. Canetta

    2015-09-01

    Full Text Available Adult-onset nephrotic syndrome differs from its pediatric counterpart in several important ways. Most importantly, nephrotic syndrome in adults is more etiologically heterogeneous compared to children, and thus treatment approaches rely heavily on the histologic diagnosis provided by renal biopsy. The evidence-based approach to treatment of adult nephrotic syndrome has been critically examined by the Kidney Disease Improving Global Outcomes (KDIGO guidelines in glomerulonephritis, published in 2012. Here, we examine the strengths and limits of those guidelines and review recent work that expands the evidence-based approach.

  19. Late-Onset Nephrotic Syndrome in Galloway-Mowat Syndrome: A Case Report

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    Hazza Issa

    1999-01-01

    Full Text Available Galloway-Mowat Syndrome (GMS has a wide variety of clinical manifestations and histologic findings. All reported cases had developed nephrotic syndrome in the first two years of life. We report a case of 12 years old boy with microcephaly, mental retardation, and typical dysmorphic features of GMS with a late onset of minimal change nephritic syndrome which first manifested at seven years of age.

  20. Nephrotic syndrome with a nephritic component associated with toxoplasmosis in an immunocompetent young man.

    OpenAIRE

    Barrios, Julio E; Duran Botello, Claudia; González Velásquez, Tania

    2012-01-01

    Introduction: Although the association of infection by toxoplasmosis with the development of nephrotic syndrome is uncommon, cases of this association have nevertheless been reported in the literature for more than two decades, not only for congenital toxoplasmosis, but also in acquired cases, and occasionally in immunocompetent patients. Development: A case is presented of an immunocompetent patient aged 15 with clinical and laboratory indications of nephrotic/nephritic syndrome, in whom ser...

  1. Superior sagittal sinus thrombosis: a rare complication in a child with nephrotic syndrome

    International Nuclear Information System (INIS)

    Pirogovsky, A.; Adi, M.; Barzilai, N.; Dagan, A.; Sinai, L.; Sthoeger, D.; Tabachnik, E.

    2001-01-01

    A 2-year-old boy with new-onset nephrotic syndrome developed recurrent vomiting, apathy and papilloedema. Superior sagittal sinus thrombosis was diagnosed on cranial CT and MRI. He gradually recovered after treatment with heparin, fresh frozen plasma and warfarin with complete resolution of the thrombosis after 1 month. Superior sagittal sinus thrombosis is an extremely rare complication of nephrotic syndrome in children. Early diagnosis is essential for institution of anticoagulation therapy and a successful outcome. (orig.)

  2. Superior sagittal sinus thrombosis: a rare complication in a child with nephrotic syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Pirogovsky, A.; Adi, M.; Barzilai, N. [Dept. of Radiology, Kaplan Medical Center, Rehovot (Israel); Dagan, A.; Sinai, L.; Sthoeger, D. [Div. of Paediatrics, Kaplan Medical Center, Rehovot (Israel); Tabachnik, E. [Div. of Paediatrics, Kaplan Medical Center, Rehovot (Israel); Paediatric ICU, Kaplan Hospital, Rehovot (Israel)

    2001-10-01

    A 2-year-old boy with new-onset nephrotic syndrome developed recurrent vomiting, apathy and papilloedema. Superior sagittal sinus thrombosis was diagnosed on cranial CT and MRI. He gradually recovered after treatment with heparin, fresh frozen plasma and warfarin with complete resolution of the thrombosis after 1 month. Superior sagittal sinus thrombosis is an extremely rare complication of nephrotic syndrome in children. Early diagnosis is essential for institution of anticoagulation therapy and a successful outcome. (orig.)

  3. A rare association of Castleman′s disease and nephrotic syndrome

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    I Tazi

    2011-01-01

    Full Text Available Castleman′s Disease (CD is an uncommon and poorly understood disorder of lymph node hyperplasia of unknown etiology. This entity belongs to the atypical lymphoproliferative disorders, a heterogeneous group of diseases characterized by a hyperplastic reactive process involving the immune system. The association of the nephrotic syndrome and CD is extremely rare and their interrelation remains enigmatic. We report a case of CD of the hyaline-vascular type with unicentric localization complicated by nephrotic syndrome.

  4. Profound nephrotic syndrome in a patient with ovarian teratoma

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    Abdallah Jeroudi

    2013-01-01

    Full Text Available The nephrotic syndrome (NS has been associated with a variety of malignancies in a number of reports in the literature, but has been reported in only nine cases associated with ovarian neoplasms. Membranous nephropathy is the most common glomerular pathology causing the NS in patients with solid tumors. There has been only one report of an ovarian neoplasm associated with minimal change disease (MCD. We describe the case of a 36-year-old woman who presented with the NS secondary to biopsy-proven MCD, likely secondary to mature ovarian teratoma. Treatment by tumor removal and prednisone led to remission of the NS. To the best of our knowledge, this is the first report of an ovarian teratoma and the second report of an ovarian neoplasm associated with MCD.

  5. Toxic epidermal necrolysis associated with deflazacort therapy with nephrotic syndrome

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    Eun Chae Lee

    2014-12-01

    Full Text Available Toxic epidermal necrolysis (TEN is a drug-related fatal disease. Extensive necrosis of the epidermis can lead to serious complications. This report describes two cases of TEN, associated with deflazacort (DFZ, in two boys, aged 4 years and 14 years, with nephrotic syndrome (NS. The 14-year-old male teenager received DFZ following NS relapse. After 17 days, pruritic papules appeared on the lower extremities. Another case involved a 4-year-old boy receiving DFZ and enalapril. After a 41-day DFZ treatment period, erythematous papules appeared on the palms and soles. Within 3 days, both boys developed widespread skin lesions (>50% and were admitted to the intensive care unit for resuscitative and supportive treatment. The patients showed improvement after intravenous immunoglobulin-G therapy. Owing to the rapid, fatal course of TEN, clinicians need to be aware of the adverse effects of this drug when treating cases of NS.

  6. Childhood Idiopathic Steroid Resistant Nephrotic Syndrome, Different Drugs and Outcome

    International Nuclear Information System (INIS)

    Shah, S. S. H.; Hafeez, F.

    2016-01-01

    Background: The management of steroid resistant nephrotic syndrome (SRNS) is quite difficult in paediatric patients. Not only the remission is difficult but also these patients are at risk of progression to end stage renal disease (ESRD). The goal of treatment is either to achieve complete remission or even partial remission as it is the most important predictor of disease outcome. Methods: This study was conducted at The Children Hospital, Lahore from February 2014 to May 2015. The SRNS patients of either sex between ages of 1-12 years were included with histology showing mesangioproliferative glomerulonephritis (MesangioPGN), focal segmental glomerulosclerosis (FSGS) or minimal change disease (MCD). Patients were given different immunosuppressant drugs and steroid 30 mg/m/sup 2/ alternate day therapy on case to case basis and kept on regular follow up to check for response and adverse effects. Results: Total of 105 patients included, 63 (60 percent) male and 42 (40 percent) female patients. The age ranges from 1.08 to 12 years, mean age of 6.53 years and SD of ±3.17. Tacrolimus was the most common drug used 43 (41 percent) patients followed by cyclosporine in 38 (36.2 percent) patients, while Mycophenolate mofetil (MMF) was prescribed in 21 (20 percent) patients. Complete response was in 96 (91.4 percent) initially while partial response was seen in 8 (7.6 percent) patients. On follow up, 92 (87.6 percent) patients showed complete response and partial response was in 5 (4.7 percent) patients. Cushingoid features and hypertrichosis were the most common adverse effect seen. Conclusion: Steroid resistant nephrotic syndrome can be managed well with various immunosuppressant drugs and steroids but treatment should be individualized according to clinical presentation, disease histology and cost/social factors. (author)

  7. Idiopathic Nephrotic Syndrome in Childhood: A Retrospective Analysis of Two Hundred and Eighty Nine Patients

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    Kenan Yılmaz

    2017-12-01

    Full Text Available Aim: In this study, we aimed to evaluate the demographic and histopathological characteristics and response to medications in children with idiopathic nephrotic syndrome in Turkey. Methods: We reviewed medical records of patients older than one year, who were newly diagnosed with nephrotic syndrome and had been followed for at least one year in our department between November 1994 and March, 2013. Results: A total of 289 children (169 boys were included in the study. Fifty theree patients (18.4% were with steroid-resistant nephrotic syndrome, 33 (11.4% with frequently relapsing nephrotic syndrome and 53 (18.4% were with steroid-dependent nephrotic syndrome. Cyclosporine A (CsA, cyclophosphamide, mycophenolate mofetil, levamisole, azathioprine, and rituximab were used as steroid-sparing agents in some patients. The number of patients who were responder to steroid and to CsA was similar. Majority of patients with steroid-resistant nephrotic syndrome were also resistant to mycophenolate mofetil and CsA. Conclusion: There was a high prevalence of minimal change disease based on kidney biopsy especially in boys younger than six years of age and response to steroid and CsA was almost similar.

  8. Sonography and dynamic scintigraphy with 99mTc-DTPA in children with nephrotic syndrome

    International Nuclear Information System (INIS)

    Bliznakova, D.; Klisarove, A.

    2000-01-01

    The aim of the study is to assay the clinical application of kidney sonography and dynamic scintigraphy with 99m Tc-DTPA in children presenting nephrotic syndrome. A total of 32 children (mean age 9.5±1.2) are covered by the study, with the most important laboratory investigations being performed. All patients undergo abdominal sonography and dynamic kidney scintigraphy following iv administration of 100 μC/kg 99m Tc-DTPA, and glomerular filtration clarence (GFR) measured by the method of full and empty syringe activity. The functional curves are also shown. In children with primary nephrotic syndrome the sonographic imaging reveals enlarged kidney size and enhanced sonogeneity of parenchyma in the first stage. In patients with secondary nephrotic syndrome increased kidney size is likewise observed with enhanced sonogeneity of parenchyma in second stage and unclear visualization of pyramids. In children with idiopathic nephrotic syndrome the scintigraphic data confirm the enlarged kidneys with moderately increased values of GFR. In the mixed forms of nephrotic syndrome the kidneys preserve their moderate enlargement against the background of heterogeneous GFR values. In 5 patients the functional curves show kidney excretion impairment. The study confirms that sonographic imaging correlates well with the dynamic scintigraphic 99m Tc-DTPA imaging in children with nephrotic syndrome. The functional curves and GFR values promote accurate diagnosing and monitoring of the dynamic pathological processes. (author)

  9. Children with Steroid-resistant Nephrotic Syndrome: a Single-Center Study

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    Rahime Renda

    2016-01-01

    Full Text Available Background and Aim: Steroid-resistant nephrotic syndrome (SRNS accounts for 10%-20% of all cases of idiopathic nephrotic syndrome. These patients are at risk of developing end-stage renal disease. The aim of this study was to determine the demographic characteristics, renal biopsy findings, response to immunosuppressive treatment, and prognosis in pediatric patients with SRNS.Materials and Methods: This retrospective study included 31 patients diagnosed as primary SRNS. Age at first episode, gender, parental consanguinity, and familial history of nephrotic syndrome were recorded. Demographic characteristics, renal biopsy findings, response to immunosuppressive treatment, and prognosis were analyzed, as were the number of and treatment of relapses, extra-renal manifestations, and complications of disease and treatment.Results: Mean age at first episode of nephrotic syndrome was 4,1±2,9 years. At the end of the first immunosuppressive treatment cycle, 14 (51.8% patients achieved complete remission, 4 (14.8% patients achieved partial remission, and 9 patients (33.3% did not achieve remission. Analysis of the final status of the patients showed that 16 patients (51.6% developed remission, 5 patients (16% continued to have nephrotic range proteinuria and 10 patients (32% developed chronic renal failure (CRF.Conclusion: The treatment of SRNS remains controversial. Early genetic testing can help the inevitable immunosuppressive treatments which may not be effective and have several side effects. Calcineurin inhibitors and mycophenolate mofetil are known to be effective immunosuppressive drugs for treating steroid resistant nephrotic syndrome .

  10. Successful treatment of dwarfism secondary to long-term steroid therapy in steroid-dependent nephrotic syndrome.

    Science.gov (United States)

    Sun, Linlin; Chen, Dongping; Zhao, Xuezhi; Xu, Chenggang; Mei, Changlin

    2010-01-01

    Prolonged steroid therapy is generally used for steroid-dependent nephrotic syndrome in pediatric patients. However, dwarfism secondary to a long-term regimen and its successful reverse is rarely reported. The underlying mechanism of dwarfism is still poorly understood, as both long-term steroid use and nephrotic syndrome may interact or independently interfere with the process of growth. Here, we present a 17-year-old patient with dwarfism and steroid-dependent nephrotic syndrome and the successful treatment by recombinant human growth factor and cyclosporine A with withdrawal of steroid. We also briefly review the current understanding and the management of dwarfism in pediatric patients with nephrotic syndrome.

  11. Neutrophil chemokines levels in different stages of nephrotic syndrome

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    Ashwag S Alsharidah

    2017-01-01

    Full Text Available Nephrotic syndrome (NS is a disease of glomerular filtration barrier failure presenting with variable degrees of proteinuria, hypoalbuminemia, hyperlipidemia, and edema. Inflammation may contribute to the pathogenesis of NS. The aim of this study was to monitor the serum levels of three cytokines [i.e., granulocyte chemotactic protein-2 (GCP-2, growth-related oncogene-α (GRO-α, and interleukin-8 (IL-8] in different stages of NS and to find out whether changes in the levels of these cytokines could be related to the severity of NS. This study included 125 patients who were divided into 40 patients with nephrotic range proteinuria (NRP, 45 patients with NS, and 40 patients who were in remission. This study also included 80 healthy participants as a control group. Enzyme-linked immunosorbent assay was used for the determination of the plasma levels of GRO-α, GCP-2, and IL-8. GCP-2 plasma levels were significantly higher in the NS and NRP groups when compared to the control group, whereas the GRO-α and IL-8 levels were significantly higher in all patient groups in comparison with the control group. All these chemokine levels were significantly decreased in remission as compared with the participants in the NS group (P <0.0001. There was a significant correlation between the cytokine levels and proteinuria and serum albumin in the NS group (P <0.0001. However, in the follow-up group, GCP-2 levels were significantly lower during remission as compared to those with active NS (P <0.0001. Our findings suggest that the pro-inflammatory cytokines GCP-2, GRO-α, and IL-8 could play a role in the pathogenesis of NS, particularly glomerular permeability.

  12. Correlation between Oxidative Stress and Thyroid Function in Patients with Nephrotic Syndrome

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    Sangita U. Sawant

    2011-01-01

    Full Text Available Background. The present study is to look for a correlation between oxidative stress and thyroid function in patients with the nephrotic syndrome in the remission phase as well as in a persistent proteinuric state. Introduction. Nephrotic syndrome is a form of chronic kidney disease due to which blood loses protein through the urine. We wanted to know if there was an increased loss of thyroid hormones in urine affecting thyroid function. Methods. 60 patients with nephrotic syndrome and 20 healthy non-proteinuric individuals as control subjects were enrolled in the study. We measured their serum tri-iodothyronine, thyroxine and thyroid-stimulating hormone. Estimation of lipid peroxidation (LPx catalase, superoxide dismutase (SOD, and Glutathione peroxidase (GPx were carried out by standard methods. Results. TSH was elevated in the nephrotic patients compared to controls, while TT4 and TT3 were significantly lower in the patients than in controls. Lipid Peroxidation and GPx were significantly higher in the nephrotic syndrome patients than in the controls, while SOD and catalase were significantly lower than in patients than in the control subjects. Conclusion. Nephrotic patients can lose significant amounts of thyroid hormones along with protein in urine, which can affect thyroid status, but this is reversible on remission.

  13. Surgical abdomen in patients with nephrotic syndrome: complexities of differential diagnostics. 2 case reports

    OpenAIRE

    Nogaibayeva, A.; Moldakhmetova, S.; Tuganbekova, S.; Krivoruchko, N.

    2014-01-01

    INTROduCTIONANdAIMS: Differential-diagnostic search is very important at the stage of abdominal nephrotic crisis for determination of therapy tactics; as the probability of development of acute surgical pathology is very high, due to connection of infectious complications on a background of the basic pathology and immunosupression. We report 2 patients with acute onset of abdominal pain on a background of severe nephrotic syndrome (NS). METHOdS: Case 1: 20-years old man with bioptic diagnosis...

  14. The role of novel biomarkers in childhood idiopathic nephrotic syndrome: a narrative review of published evidence

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    Uwaezuoke SN

    2017-06-01

    Full Text Available Samuel N Uwaezuoke Department of Pediatrics, Pediatric Nephrology Firm, University of Nigeria Teaching Hospital, Ituku-Ozalla, Enugu, Nigeria Abstract: Two histological subtypes of idiopathic nephrotic syndrome are commonly recognized in children, namely minimal change nephropathy and focal segmental glomerulosclerosis. Children with minimal change nephropathy (the majority of whom are steroid-sensitive and focal segmental glomerulosclerosis (the majority of whom are steroid-resistant require early identification in order to ensure appropriate therapeutic intervention and better outcome. Although renal biopsy and histology remain the ideal diagnostic steps to identify these histological subtypes, reports indicate that serum and urinary biomarkers are now being utilized in the investigation of childhood idiopathic nephrotic syndrome. This paper aims to review the diagnostic and prognostic utility of novel biomarkers in childhood idiopathic nephrotic syndrome and to highlight their role in differentiating steroid-sensitive nephrotic syndrome (SRNS from steroid-resistant nephrotic syndrome (SSNS. Using the terms “idiopathic nephrotic syndrome,” “children,” and “biomarkers” the PubMed database was searched for relevant studies related to the topic. Biomarkers such as adiponectin, neopterin, β2-microglobulin, and N-acetyl-β-D glucosaminidase were reported as diagnostic markers. In addition to neopterin and N-acetyl-β-D glucosaminidase, urine vitamin D-binding protein and α1β-glycoprotein were shown to differentiate SRNS from SSNS while N-acetyl-β-D glucosaminidase and β2-microglobulin could predict steroid responsiveness and renal outcome in SRNS. Although progress has been made in demonstrating the diagnostic and prognostic utility of these biomarkers, their limited availability in most laboratories has precluded a complete paradigm shift from the conventional renal biopsy. Nevertheless, further longitudinal studies are required

  15. Determinants of plasma homocyst(e)ine in patients with nephrotic syndrome.

    Science.gov (United States)

    Joven, J; Arcelús, R; Camps, J; Ordóñez-Llanos, J; Vilella, E; González-Sastre, F; Blanco-Vaca, F

    2000-01-01

    Hyperhomocyst(e)inemia is an independent risk factor for atherothrombosis in several clinical settings in which renal function is impaired, but its prevalence in the nephrotic syndrome has not been investigated in detail, even though this syndrome provides an excellent model in which to study a possible link between albuminuria, proteinuria, and hyperhomocyst(e)inemia. We obtained plasma and urine from 27 patients with biopsy-confirmed membranous glomerulonephritis presenting nephrotic syndrome and 27 matched controls and determined the concentrations of homocyst(e)ine and proteins considered putative markers of glomerular and tubular function. Hyperhomocyst(e)inemia, defined as the mean +SD of the plasma homocyst(e)ine concentration of the controls [plasma homocyst(e)ine concentration >10.8 micromol/l] was present in 26% of the patients with nephrotic syndrome but in only 7.4% of the controls. Furthermore, the degree of hyperhomocyst(e)inemia was more severe in the nephrotic patients than in the controls. The existence of renal failure, tubular damage, and, interestingly, relatively well conserved glomerular function barrier were the main predictors of increased levels of plasma homocyst(e)ine. In conclusion, hyperhomocyst(e)inemia is a frequent cardiovascular risk factor present in patients with nephrotic syndrome and renal failure, but it is not directly associated with proteinuria.

  16. Low molecular weight heparin may benefit nephrotic remission in steroid‑sensitive nephrotic syndrome via inhibiting elastase.

    Science.gov (United States)

    Zhai, Songhui; Hu, Lijuan; Zhong, Lin; Tao, Yuhong; Wang, Zheng

    2017-12-01

    Low molecular weight heparin (LMWH) has a structure similar to heparan sulfate, which exerts anti‑inflammatory effects via inhibiting elastase (Ela) activity. Release of Ela along the glomerular capillary wall may induce glomerular injury and proteinuria. The present study aimed to investigate the influence of LMWH on steroid‑sensitive nephrotic syndrome (SSNS) and the potential underlying mechanism. A total of 40 SSNS patients and 20 healthy controls were recruited. SSNS patients were treated with LMWH and prednisone simultaneously (LMWH+pred group) or with prednisone alone (pred group). Proteinuria, urinary glycosaminoglycans (GAGs), serum Ela and urinary creatinine levels were measured. The nephrotic period of SSNS was 15.93±5.78 days. The nephrotic period of SSNS in LMWH+pred group was significantly reduced compared with the pred group (14.13±4.56 vs. 18.63±6.49 days; PEla levels (77.64±10.99 ng/l) were significantly greater in the nephrotic period of SSNS compared with the remission period (0.107±0.026 g/24 h, 1.53±0.27 mg/mmol Cr and 41.92±7.81 ng/l, respectively) and the healthy control group (0.098±0.027 g/24 h, 1.40±0.26 mg/mmol creatinine and 38.43±9.83 ng/l, respectively; PEla levels in the LMWH+pred group were significantly reduced compared with the pred group (P0.05). Positive correlations were revealed between urinary GAG excretion and proteinuria (r=0.877; PEla levels (r=0.844; PEla levels and urinary GAG excretion (r=0.881; PEla levels may induce proteinuria by degrading GAGs in the glomerular basement membrane in children with SSNS. LMWH may benefit nephrotic remission of SSNS via inhibiting Ela.

  17. Histopathological patterns in paediatric idiopathic steroid resistant nephrotic syndrome

    International Nuclear Information System (INIS)

    Shah, S.S.H.; Akhtar, N.; Rehman, M.F.U.; Sunbleen, F.; Ahmed, T.

    2015-01-01

    Background: Steroid-resistant nephrotic syndrome (SRNS) is a common problem but difficult to treat for pediatric nephrologists. Due to paucity of studies done in few centres in southern Pakistan regarding the histopathological aspects in paediatric patients with SRNS, this study was conducted to determine the histopathological spectrum in children with SRNS at our centre. Method: This descriptive study has been conducted at the Nephrology department, The Children's Hospital Lahore from February 2014 to January 2015. Based upon history, physical examination and laboratory results, all patients diagnosed as idiopathic SRNS were included in the study and renal biopsy was done to determine the underlying pathology. Histopathology reports were retrieved and data analysis done using SPSS-20.0. Results: There were a total of 96 patients, 64 (66.7 percentage) males and 32 (33.3 percentage) females. The age range was from 0.80 to 15 years with mean age of presentation being 6.34+3.75 years. The most common histo-pathological pattern was mesangio-proliferative Glomerulonephritis found in 79 (82.3 percentage) cases followed by Focal segmental glomerulosclerosis (FSGS) in 9 (9.4 percentage) patients while Minimal change disease (MCD) was seen in 5 (5.2 percentage) subjects. Conclusion: Mesangioproliferative glomerulonephritis is the most common histological pattern seen in children presenting with idiopathic SRNS at our centre followed by FSGS and MCD. (author)

  18. Pathophysiology, Evaluation, and Management of Edema in Childhood Nephrotic Syndrome

    Science.gov (United States)

    Ellis, Demetrius

    2016-01-01

    Generalized edema is a major presenting clinical feature of children with nephrotic syndrome (NS) exemplified by such primary conditions as minimal change disease (MCD). In these children with classical NS and marked proteinuria and hypoalbuminemia, the ensuing tendency to hypovolemia triggers compensatory physiological mechanisms, which enhance renal sodium (Na+) and water retention; this is known as the “underfill hypothesis.” Edema can also occur in secondary forms of NS and several other glomerulonephritides, in which the degree of proteinuria and hypoalbuminemia, are variable. In contrast to MCD, in these latter conditions, the predominant mechanism of edema formation is “primary” or “pathophysiological,” Na+ and water retention; this is known as the “overfill hypothesis.” A major clinical challenge in children with these disorders is to distinguish the predominant mechanism of edema formation, identify other potential contributing factors, and prevent the deleterious effects of diuretic regimens in those with unsuspected reduced effective circulatory volume (i.e., underfill). This article reviews the Starling forces that become altered in NS so as to tip the balance of fluid movement in favor of edema formation. An understanding of these pathomechanisms then serves to formulate a more rational approach to prevention, evaluation, and management of such edema. PMID:26793696

  19. Cyclosporine/ketoconazole reduces treatment costs for nephrotic syndrome

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    A Iyengar

    2013-01-01

    Full Text Available Cyclosporine A (CyA is an effective agent for the treatment of glucocorticoid-dependent idiopathic nephrotic syndrome (GCDNS, but costs are prohibitive in resource-poor societies. The objectives of this study were to evaluate the efficacy and safety of reducing the dose of CyA by co-administering ketoconazole. A prospective study targeting children 2-18 years of age with GCDNS in remission with CyA monotherapy was conducted. CyA dose was reduced by 50% and ketoconazole was added at 25% of the recommended therapeutic dose, and the drug levels and therapeutic and adverse effects (AE were monitored. Continued combined therapy after completion of the 4-week trial period was offered. Ten patients (median age 9.5 years, range 3.0-16.0 years were enrolled in the study. At week 4, the CyA dose was 2.2 ± 0.7 mg/kg/day compared with 5.6 ± 0.9 mg/kg/day at enrolment ( P 50% without increased adverse events or drug monitoring needs. This intervention demonstrates how access of patients with limited resources to needed drugs can be improved by interference with physiological drug elimination.

  20. The impact of pediatric nephrotic syndrome on families.

    Science.gov (United States)

    Mitra, Sulagna; Banerjee, Sushmita

    2011-08-01

    The objective of our study was to assess the psychologic and economic effects of pediatric nephrotic syndrome (NS) on caregivers. Caregivers of 50 children with NS were compared with a control group of 50 families of children with minor illnesses attending the same outpatient facility. Beck's Depression Inventory (BDI) IA was used to assess the mental status of the primary caregiver. The socioeconomic status of the family was assessed using the modified Kuppuswamy scale. Expenditure for the illness was calculated during parent interviews. The difference between groups was analyzed using analysis of variance (ANOVA) and Duncan's multiple range test. BDI scores signified moderate to severe depression in 48% of NS caregivers compared with 12% controls. The mean BDI score was significantly higher in NS caregivers, correlating positively with disease severity and negatively with socioeconomic status. Expenditure for disease also was significantly higher in families with NS patients, varying between 30% and 60% of monthly income depending on disease severity compared with 6.9% in controls. In 10% of NS families, it was more than total income, forcing families to break into savings or go into debt. Although pediatric NS most commonly has an excellent long-term outcome, it causes significant mental and economic stress on families. Severe forms should be categorized as a chronic illness and be eligible for disability benefits and subsidized travel and medical care. Establishing support groups and supportive care at local levels would help reduce the burden on families of patients wtih NS.

  1. Hepatitis B viral infection with nephrotic syndrome treated with lamivudine.

    Science.gov (United States)

    Banu, N A; Khatoon, S; Quadir, E; Rahman, M M; Khan, M A

    2007-07-01

    A 04 years old boy with 02 months history of generalized oedema and scanty micturition was diagnosed as nephrotic syndrome with hepatitis B viral infection. He had evidence of active viral replication. After 01 month treatment with oral lamivudine, his urine became protein free and after 04 months, he had seroconversion from HBeAg+ve to HBeAg-ve. Lamivudine was continued for 01 year. He had no relapse after discontinuation of therapy and remained well after 36 months of completion of therapy. He had no evidence of active viral replication during this period, however HBsAg remained positive indication carrier state. As most children with HBV associated nephropathy have no evidence of chronic hepatitis, all such children must undergo HBV screening and for chronic liver disease if HBV screening is positive. As such children do not respond to prednisolone or other immunosuppresive therapy which might harm them, antiviral therapy should be considered. Lamivudine is a suitable alternative to IFN alpha owing to its low cost, ease of administration and fewer side effects.

  2. Pathophysiology, Evaluation, and Management of Edema in Childhood Nephrotic Syndrome.

    Science.gov (United States)

    Ellis, Demetrius

    2015-01-01

    Generalized edema is a major presenting clinical feature of children with nephrotic syndrome (NS) exemplified by such primary conditions as minimal change disease (MCD). In these children with classical NS and marked proteinuria and hypoalbuminemia, the ensuing tendency to hypovolemia triggers compensatory physiological mechanisms, which enhance renal sodium (Na(+)) and water retention; this is known as the "underfill hypothesis." Edema can also occur in secondary forms of NS and several other glomerulonephritides, in which the degree of proteinuria and hypoalbuminemia, are variable. In contrast to MCD, in these latter conditions, the predominant mechanism of edema formation is "primary" or "pathophysiological," Na(+) and water retention; this is known as the "overfill hypothesis." A major clinical challenge in children with these disorders is to distinguish the predominant mechanism of edema formation, identify other potential contributing factors, and prevent the deleterious effects of diuretic regimens in those with unsuspected reduced effective circulatory volume (i.e., underfill). This article reviews the Starling forces that become altered in NS so as to tip the balance of fluid movement in favor of edema formation. An understanding of these pathomechanisms then serves to formulate a more rational approach to prevention, evaluation, and management of such edema.

  3. Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly

    NARCIS (Netherlands)

    Braun, Daniela A; Rao, Jia; Mollet, Geraldine; Schapiro, David; Daugeron, Marie-Claire; Tan, Weizhen; Gribouval, Olivier; Boyer, Olivia; Revy, Patrick; Jobst-Schwan, Tilman; Schmidt, Johanna Magdalena; Lawson, Jennifer A; Schanze, Denny; Ashraf, Shazia; Ullmann, Jeremy F P; Hoogstraten, Charlotte A; Boddaert, Nathalie; Collinet, Bruno; Martin, Gaëlle; Liger, Dominique; Lovric, Svjetlana; Furlano, Monica; Guerrera, I Chiara; Sanchez-Ferras, Oraly; Hu, Jennifer F; Boschat, Anne-Claire; Sanquer, Sylvia; Menten, Björn; Vergult, Sarah; De Rocker, Nina; Airik, Merlin; Hermle, Tobias; Shril, Shirlee; Widmeier, Eugen; Gee, Heon Yung; Choi, Won-Il; Sadowski, Carolin E; Pabst, Werner L; Warejko, Jillian K; Daga, Ankana; Basta, Tamara; Matejas, Verena; Scharmann, Karin; Kienast, Sandra D; Behnam, Babak; Beeson, Brendan; Begtrup, Amber; Bruce, Malcolm; Ch'ng, Gaik-Siew; Lin, Shuan-Pei; Chang, Jui-Hsing; Chen, Chao-Huei; Cho, Megan T; Gaffney, Patrick M; Gipson, Patrick E; Hsu, Chyong-Hsin; Kari, Jameela A; Ke, Yu-Yuan; Kiraly-Borri, Cathy; Lai, Wai-Ming; Lemyre, Emmanuelle; Littlejohn, Rebecca Okashah; Masri, Amira; Moghtaderi, Mastaneh; Nakamura, Kazuyuki; Ozaltin, Fatih; Praet, Marleen; Prasad, Chitra; Prytula, Agnieszka; Roeder, Elizabeth R; Rump, Patrick; Schnur, Rhonda E; Shiihara, Takashi; Sinha, Manish D; Soliman, Neveen A; Soulami, Kenza; Sweetser, David A; Tsai, Wen-Hui; Tsai, Jeng-Daw; Topaloglu, Rezan; Vester, Udo; Viskochil, David H; Vatanavicharn, Nithiwat; Waxler, Jessica L; Wierenga, Klaas J; Wolf, Matthias T F; Wong, Sik-Nin; Leidel, Sebastian A; Truglio, Gessica; Dedon, Peter C; Poduri, Annapurna; Mane, Shrikant; Lifton, Richard P; Bouchard, Maxime; Kannu, Peter; Chitayat, David; Magen, Daniella; Callewaert, Bert; van Tilbeurgh, Herman; Zenker, Martin; Antignac, Corinne; Hildebrandt, Friedhelm

    2017-01-01

    Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS

  4. The clinical value of pulmonary perfusion imaging complicated with pulmonary embolism in children of nephrotic syndrome

    International Nuclear Information System (INIS)

    Lin Jun; Chen Ning; Miao Weibing; Peng Jiequan; Jiang Zhihong; Wu Jing

    2001-01-01

    To investigate the clinical features of complicated with pulmonary embolism nephrotic syndrome in children. 99m Tc-MAA pulmonary perfusion imaging was performed on 30 nephrotic syndrome in children with elevated plasma D-dimer. Results shown that 14 of 30 patients were found to have pulmonary embolism (46.7%). Pulmonary perfusion imaging showed an involvement of 1 pulmonary segment in 3 cases, 2 segments in 2 cases and over 3 segments in other 9 cases. Among them, there were 7 segments involved in one case. After two weeks of heparin anti-coagulative therapy, most cases showed a recovery. The result of this study suggested that pulmonary embolism is a common complication of nephrotic syndrome. Pulmonary perfusion imaging is simple, effective and accurate method for the diagnosis of pulmonary embolism, and it also can help to assess the value of clinical therapy

  5. Nephroprotective effect of heparanase in experimental nephrotic syndrome.

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    Suheir Assady

    Full Text Available Heparanase, an endoglycosidase that cleaves heparan sulfate (HS, is involved in various biologic processes. Recently, an association between heparanase and glomerular injury was suggested. The present study examines the involvement of heparanase in the pathogenesis of Adriamycin-induced nephrotic syndrome (ADR-NS in a mouse model.BALB/c wild-type (wt mice and heparanase overexpressing transgenic mice (hpa-TG were tail-vein injected with either Adriamycin (ADR, 10 mg/kg or vehicle. Albuminuria was investigated at days 0, 7, and 14 thereafter. Mice were sacrificed at day 15, and kidneys were harvested for various analyses: structure and ultrastructure alterations, podocyte proteins expression, and heparanase enzymatic activity.ADR-injected wt mice developed severe albuminuria, while ADR-hpa-TG mice showed only a mild elevation in urinary albumin excretion. In parallel, light microscopy of stained cross sections of kidneys from ADR-injected wt mice, but not hpa-TG mice, showed mild to severe glomerular and tubular damage. Western blot and immunofluorescence analyses revealed significant reduction in nephrin and podocin protein expression in ADR-wt mice, but not in ADR-hpa-TG mice. These results were substantiated by electron-microscopy findings showing massive foot process effacement in injected ADR-wt mice, in contrast to largely preserved integrity of podocyte architecture in ADR-hpa-TG mice.Our results suggest that heparanase may play a nephroprotective role in ADR-NS, most likely independently of HS degradation. Moreover, hpa-TG mice comprise an invaluable in vivo platform to investigate the interplay between heparanase and glomerular injury.

  6. Nephrotic Syndrome and Idiopathic Membranous Nephropathy Associated with Autosomal-Dominant Polycystic Kidney Disease

    Science.gov (United States)

    Peces, Ramón; Martínez-Ara, Jorge; Peces, Carlos; Picazo, Mariluz; Cuesta-López, Emilio; Vega, Cristina; Azorín, Sebastián; Selgas, Rafael

    2011-01-01

    We report the case of a 38-year-old male with autosomal-dominant polycystic kidney disease (ADPKD) and concomitant nephrotic syndrome secondary to membranous nephropathy (MN). A 3-month course of prednisone 60 mg daily and losartan 100 mg daily resulted in resistance. Treatment with chlorambucil 0.2 mg/kg daily, low-dose prednisone, plus an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin II receptor blocker (ARB) for 6 weeks resulted in partial remission of his nephrotic syndrome for a duration of 10 months. After relapse of the nephrotic syndrome, a 13-month course of mycophenolate mofetil (MFM) 2 g daily and low-dose prednisone produced complete remission for 44 months. After a new relapse, a second 24-month course of MFM and low-dose prednisone produced partial to complete remission of proteinuria with preservation of renal function. Thirty-six months after MFM withdrawal, complete remission of nephrotic-range proteinuria was maintained and renal function was preserved. This case supports the idea that renal biopsy is needed for ADPKD patients with nephrotic-range proteinuria in order to exclude coexisting glomerular disease and for appropriate treatment/prevention of renal function deterioration. To the best of our knowledge, this is the first reported case of nephrotic syndrome due to MN in a patient with ADPKD treated with MFM, with remission of proteinuria and preservation of renal function after more than 10 years. Findings in this patient also suggest that MFM might reduce cystic cell proliferation and fibrosis, preventing progressive renal scarring with preservation of renal function. PMID:21552769

  7. Nephrotic Syndrome and Idiopathic Membranous Nephropathy Associated with Autosomal-Dominant Polycystic Kidney Disease

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    Ramón Peces

    2011-01-01

    Full Text Available We report the case of a 38-year-old male with autosomal-dominant polycystic kidney disease (ADPKD and concomitant nephrotic syndrome secondary to membranous nephropathy (MN. A 3-month course of prednisone 60 mg daily and losartan 100 mg daily resulted in resistance. Treatment with chlorambucil 0.2 mg/kg daily, low-dose prednisone, plus an angiotensin-converting enzyme inhibitor (ACEI and an angiotensin II receptor blocker (ARB for 6 weeks resulted in partial remission of his nephrotic syndrome for a duration of 10 months. After relapse of the nephrotic syndrome, a 13-month course of mycophenolate mofetil (MFM 2 g daily and low-dose prednisone produced complete remission for 44 months. After a new relapse, a second 24-month course of MFM and low-dose prednisone produced partial to complete remission of proteinuria with preservation of renal function. Thirty-six months after MFM withdrawal, complete remission of nephrotic-range proteinuria was maintained and renal function was preserved. This case supports the idea that renal biopsy is needed for ADPKD patients with nephrotic-range proteinuria in order to exclude coexisting glomerular disease and for appropriate treatment/prevention of renal function deterioration. To the best of our knowledge, this is the first reported case of nephrotic syndrome due to MN in a patient with ADPKD treated with MFM, with remission of proteinuria and preservation of renal function after more than 10 years. Findings in this patient also suggest that MFM might reduce cystic cell proliferation and fibrosis, preventing progressive renal scarring with preservation of renal function.

  8. Central Nervous System (CNS Disease Triggering Takotsubo Syndrome

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    Josef Finsterer

    2016-01-01

    Full Text Available Takotsubo syndrome (TTS is usually triggered by psychological or physical stress. One of the many physical sources of stress are central nervous system (CNS disorders. CNS disorders most frequently triggering TTS include subarachnoid bleeding, epilepsy, ischemic stroke, migraine, and intracerebral bleeding. More rare CNS-triggers of TTS include posterior reversible encephalopathy syndrome (PRES, amyotrophic lateral sclerosis, encephalitis, or traumatic brain or spinal cord injury. TTS triggered by any of the CNS disorders needs to be recognized since adequate treatment of TTS may improve the general outcome from the CNS disorder as well. Neurologists need to be aware of TTS as a complication of specific CNS disorders but TTS may be triggered also by CNS disorders so far not recognised as causes of TTS.

  9. Simplified quantification of urinary protein excretion in children with nephrotic syndrome

    International Nuclear Information System (INIS)

    Mustafa, G.; Khan, P.A.; Hussain, Z.; Iqbal, M.

    2007-01-01

    To assess the value of single voided random (spot) urinary protein to creatinine ratio in accurately predicting the 24-hour urinary protein excretion in Pakistani pediatric population with nephrotic syndrome. Fifty seven children between 1-18 years with nephrotic syndrome were included. Seventy pairs of spot urine (5 milliliter) and 24-hour urine were collected in different phases of their disease e.g. initial, induction and remission. The protein to creatinine ratio was determined in spot urine samples and total protein content in 24-hour urine samples. The correlation between the ratio and 24-hour urinary protein excreted was determined using Pearson's coefficient (r) linear regression analysis. The protein to creatinine ratio in a spot urine sample was significantly correlated with the 24-hour urinary protein. The correlation coefficient (least square method) was found to be significant (r=0.9444). A random (spot) urinary protein to creatinine ratio of greater than 2 correlated well with the massive proteinuria (i.e. nephrotic syndrome), between 2 to 0.2 indicated glomerulopathy while a ratio of less than 0.2 was suggestive of physiological values. The random spot urinary protein to creatinine ratio can reliably be used to assess the degree of proteinuria in children with nephrotic syndrome and can replace the 24-hour urinary protein excretion/collection. (author)

  10. Circulating angiopoietin-like 4 links proteinuria with hypertriglyceridemia in nephrotic syndrome

    NARCIS (Netherlands)

    Clement, L.C.; Mace, C.; Avila-Casado, C.; Joles, J.A.; Kersten, A.H.; Chugh, S.S.

    2014-01-01

    The molecular link between proteinuria and hyperlipidemia in nephrotic syndrome is not known. We show in the present study that plasma angiopoietin-like 4 (Angptl4) links proteinuria with hypertriglyceridemia through two negative feedback loops. In previous studies in a rat model that mimics human

  11. Pattern of steroid-resistant nephrotic syndrome in children and the ...

    African Journals Online (AJOL)

    Steroid-resistant nephrotic syndrome (SRNS) remains a challenge for paediatric nephrologists. e underlying histopathology usually affects the course of the disease and the response to treatment.[1] ere is still controversy over the role of renal biopsy in the management of children with. SRNS.[2] Studies by the International ...

  12. Pattern of steroid-resistant nephrotic syndrome in children and the ...

    African Journals Online (AJOL)

    Background. Steroid-resistant nephrotic syndrome (SRNS) is a common problem in paediatric nephrology practice. There is currently little information on the spectrum of histopathological lesions in children presenting with SRNS in India and other south-east Asian countries. Objective. To determine the histopathological ...

  13. Role of the immune system in the pathogenesis of idiopathic nephrotic syndrome

    NARCIS (Netherlands)

    van den Berg, José G.; Weening, Jan J.

    2004-01-01

    Idiopathic NS (nephrotic syndrome) is characterized by massive proteinuria, due to a leak in the glomerular barrier to proteins. Genetic defects that affect the function and the composition of the glomerular capillary wall, in particular of the visceral epithelial cells, have recently been

  14. Extending prednisolone treatment does not reduce relapses in childhood nephrotic syndrome

    NARCIS (Netherlands)

    Teeninga, N.; Kist-van Holthe, J.E.; Rijswijk, N. van; Mos, N.I. de; Hop, W.C.J.; Wetzels, J.F.M.; Heijden, A.J. van der; Nauta, J.

    2013-01-01

    Prolonged prednisolone treatment for the initial episode of childhood nephrotic syndrome may reduce relapse rate, but whether this results from the increased duration of treatment or a higher cumulative dose remains unclear. We conducted a randomized, double-blind, placebo-controlled trial in 69

  15. Population pharmacokinetics of levamisole in children with steroid-sensitive nephrotic syndrome

    NARCIS (Netherlands)

    Kreeftmeijer-Vegter, A.R.; Dorlo, T.P.C.; Gruppen, M.P.; De Boer, A.; De Vries, P.J.

    2015-01-01

    Aim The aim was to investigate the population pharmacokinetics of levamisole in children with steroid-sensitive nephrotic syndrome. Methods Non-linear mixed effects modelling was performed on samples collected during a randomized controlled trial. Samples were collected from children who were

  16. Population pharmacokinetics of levamisole in children with steroid-sensitive nephrotic syndrome

    NARCIS (Netherlands)

    Kreeftmeijer-Vegter, A. R.; Dorlo, T. P. C.; Gruppen, M. P.; de Boer, A. [=Anthonius; de Vries, P. J.

    2015-01-01

    The aim was to investigate the population pharmacokinetics of levamisole in children with steroid-sensitive nephrotic syndrome. Non-linear mixed effects modelling was performed on samples collected during a randomized controlled trial. Samples were collected from children who were receiving 2.5 mg

  17. Nivolumab-associated Nephrotic Syndrome in a Patient With Renal Cell Carcinoma: A Case Report

    NARCIS (Netherlands)

    Daanen, R.A.; Maas, R.J.H.; Koornstra, R.H.; Steenbergen, E.J.; Herpen, C.M.L. van; Willemsen, A.E.C.A.B.

    2017-01-01

    INTRODUCTION: Immune checkpoint inhibitors have taken an important place in the treatment of different types of malignancies. These drugs are known to have specific immune-mediated adverse events. We describe a case of severe nephrotic syndrome secondary to treatment with nivolumab in a patient with

  18. Calcium and Vitamin D Metabolism in Pediatric Nephrotic Syndrome; An Update on the Existing Literature

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    Mohammad Esmaeeili

    2015-03-01

    Full Text Available  Minimal Change Disease (MCD is the leading cause of childhood Nephrotic Syndrome (NS. Therefore in pediatrics nephrotic syndrome, most children beyond the first year of life will be treated with corticosteroids without an initial biopsy. Children with NS often display a number of calcium homeostasis disturbances causing abnormal bone histology, including hypocalcemia, reduced serum vitamin D metabolites, impaired intestinal absorption of calcium, and elevated levels of immunoreactive parathyroid hormone (iPTH. These are mainly attributed to the loss of a variety of plasma proteins and minerals in the urine as well as steroid therapy. Early diagnosis and management of these abnormalities, could prevent the growth retardation and renal osteodystrophy that affects children with nephrotic syndrome. Here we reviewed the literature for changes of calcium and vitamin D metabolism in nephrotic syndrome and its consequences on bones, also the effect of corticosteroid and possible preventive strategies that could be done to avoid long term outcomes in children. Although the exact biochemical basis for Changes in levels of calcium and vitamin D metabolites in patients with NS remains speculative; Because of the potential adverse effects of these changes among growing children, widespread screening for vitamin D deficiency or routine vitamin D supplementation should be considered.

  19. Variability of diagnostic criteria and treatment of idiopathic nephrotic syndrome across European countries

    NARCIS (Netherlands)

    Deschênes, Georges; Vivarelli, Marina; Peruzzi, Licia; Alpay, H.; Alvaro Madrid, A.; Andersen, R.; Bald, M.; Benetti, E.; Berard, E.; Bockenhauer, D.; Boyer, O.; Brackman, D.; Dossier, C.; Ekinci, Z.; Emma, F.; Enneman, B.; Espinosa-Roman, L.; Fila, M.; Ghio, L.; Groothoff, J. W.; Guigonis, V.; Jankauskiene, A.; Kagan, M.; Kovacevic, M.; Kemper, M. J.; Levtchenko, E.; Maringhini, S.; Mir, S.; Mitsioni, A.; Mizerska-Wasiak, M.; Wasiak, K.; Moczulska, A.; Montini, G.; Murer, L.; Nuutinen, M.; Obukhova, V.; Oh, J.; Ozkaya, O.; Papalia, T.; Peco Antic, A.; Pecoraro, C.; Pena-Carrion, A.; Petrossian, E.; Pietrement, C.; Prikhodina, L.; Querfeld, U.; Rittig, S.; Saleem, M. A.; Saraga, M.; Savenkova, N.

    2017-01-01

    The aim of the surveys conducted by the Idiopathic Nephrotic Syndrome Working Group of the ESPN was to study the possible variability of treatment in Europe at different stages of the disease by means of questionnaires sent to members of the Working Group. Four surveys have been completed: treatment

  20. Familial Mediterranean fever, Inflammation and Nephrotic Syndrome: Fibrillary Glomerulopathy and the M680I Missense Mutation

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    Semerdjian Ronald J

    2003-08-01

    Full Text Available Abstract Background Familial Mediterranean fever (FMF is an autosomal recessive disease characterized by inflammatory serositis (fever, peritonitis, synovitis and pleuritis. The gene locus responsible for FMF was identified in 1992 and localized to the short arm of chromosome 16. In 1997, a specific FMF gene locus, MEFV, was discovered to encode for a protein, pyrin that mediates inflammation. To date, more than forty missense mutations are known to exist. The diversity of mutations identified has provided insight into the variability of clinical presentation and disease progression. Case Report We report an individual heterozygous for the M680I gene mutation with a clinical diagnosis of FMF using the Tel-Hashomer criteria. Subsequently, the patient developed nephrotic syndrome with biopsy-confirmed fibrillary glomerulonephritis (FGN. Further diagnostic studies were unremarkable with clinical workup negative for amyloidosis or other secondary causes of nephrotic syndrome. Discussion Individuals with FMF are at greater risk for developing nephrotic syndrome. The most serious etiology is amyloidosis (AA variant with renal involvement, ultimately progressing to end-stage renal disease. Other known renal diseases in the FMF population include IgA nephropathy, IgM nephropathy, Henoch-Schönlein purpura as well as polyarteritis nodosa. Conclusion To our knowledge, this is the first association between FMF and the M680I mutation later complicated by nephrotic syndrome and fibrillary glomerulonephritis.

  1. Randomized Clinical Trial Design to Assess Abatacept in Resistant Nephrotic Syndrome

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    Howard Trachtman

    2018-01-01

    Conclusion: This study advances efforts to validate CD80 as a therapeutic target for treatment-resistant nephrotic syndrome, and implements a precision medicine-based approach to this serious kidney condition in which the selection of a therapeutic agent is guided by the underlying disease mechanism operating in individual patients.

  2. Levamisole in steroid-sensitive nephrotic syndrome of childhood: the lost paradise?

    NARCIS (Netherlands)

    Davin, J. C.; Merkus, M. P.

    2005-01-01

    Among the different drugs used for sparing steroids in steroid-sensitive nephrotic syndrome (SSNS) with frequent relapses and steroid dependency, levamisole is the least toxic and the least expensive. However, it is neither approved for this indication nor widely used in Europe. This may be

  3. Risk factors for low bone density in pediatric nephrotic syndrome

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    Corina Lisa

    2011-04-01

    Full Text Available Background Disturbances in bone mineral metabolism and side effects of corticosteroid treatment may cause decreased bone density in patients v.ith nephrotic syndrome (NS. Objectives To compare the prevalence oflow bone mineral density (BMD in children with and 'Without NS and to assess the effect of corticosteroid treatment on bone density in NS patients.  Methods We conducted a retrospective, cohort study in children aged 5-18 years diagnosed 'With NS for more than 2 months prior to data collection, and in children v.ithout NS as a control. BMD was assessed on calcaneal bone wlith ultrasound bone densitometry. Serum calcium, albumin, creatinine and phosphate levels were also assessed. Results The prevalence of low BMD was significantly higher in NS patients than nonNS subjects, 73.3% (22 in 30 vs. 33% (11 in 33, respectively. The prevalence ratio was 6.3 (95% CI 2.1 to 18.9. NS patients had lower serum calcium levels, With mean difference of -0.17 (95% CI -0.27 to -0.07 mMollL, P<0.009, and lower serum albumin, with mean difference of  -0.88 (95% CI -1.27 to -0.49 gIL; P

  4. Modeling Monogenic Human Nephrotic Syndrome in the Drosophila Garland Cell Nephrocyte.

    Science.gov (United States)

    Hermle, Tobias; Braun, Daniela A; Helmstädter, Martin; Huber, Tobias B; Hildebrandt, Friedhelm

    2017-05-01

    Steroid-resistant nephrotic syndrome is characterized by podocyte dysfunction. Drosophila garland cell nephrocytes are podocyte-like cells and thus provide a potential in vivo model in which to study the pathogenesis of nephrotic syndrome. However, relevant pathomechanisms of nephrotic syndrome have not been studied in nephrocytes. Here, we discovered that two Drosophila slit diaphragm proteins, orthologs of the human genes encoding nephrin and nephrin-like protein 1, colocalize within a fingerprint-like staining pattern that correlates with ultrastructural morphology. Using RNAi and conditional CRISPR/Cas9 in nephrocytes, we found this pattern depends on the expression of both orthologs. Tracer endocytosis by nephrocytes required Cubilin and reflected size selectivity analogous to that of glomerular function. Using RNAi and tracer endocytosis as a functional read-out, we screened Drosophila orthologs of human monogenic causes of nephrotic syndrome and observed conservation of the central pathogenetic alterations. We focused on the coenzyme Q 10 (CoQ 10 ) biosynthesis gene Coq2 , the silencing of which disrupted slit diaphragm morphology. Restoration of CoQ 10 synthesis by vanillic acid partially rescued the phenotypic and functional alterations induced by Coq2 -RNAi. Notably, Coq2 colocalized with mitochondria, and Coq2 silencing increased the formation of reactive oxygen species (ROS). Silencing of ND75 , a subunit of the mitochondrial respiratory chain that controls ROS formation independently of CoQ 10 , phenocopied the effect of Coq2 -RNAi. Moreover, the ROS scavenger glutathione partially rescued the effects of Coq2 -RNAi. In conclusion, Drosophila garland cell nephrocytes provide a model with which to study the pathogenesis of nephrotic syndrome, and ROS formation may be a pathomechanism of COQ2 -nephropathy. Copyright © 2017 by the American Society of Nephrology.

  5. Corticosteroids and obesity in steroid-sensitive and steroid-resistant nephrotic syndrome

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    Nina Lestari

    2015-07-01

    Full Text Available Background Children with nephrotic syndrome need high-dose corticosteroids to achieve remission. Studies have estimated a 35-43% risk of obesity in these patients after corticosteroid treatment. Objective To determine the prevalence of obesity in children who received corticosteroids for nephrotic syndrome, and to compare the risk of obesity in children with steroid-sensitive nephrotic syndrome (SSNS and steroid-resistant nephrotic syndrome (SRNS. Methods We performed a retrospective cohort study in 50 children with SSNS or SRNS who received corticosteroid treatment. Obesity was defined to be a BMI-for-age Z-score above +2.0 SD, according to the WHO Growth Reference 2007. Central obesity was defined to be a waist-to-height ratio > 0.50. Results The overall prevalence of obesity was 22%, with 29% and 14% in the SSNS and SRNS groups, respectively. The overall prevalence of central obesity was 50%, with 54% and 46% in the SSNS and SRNS groups, respectively. The cumulative steroid doses in this study were not significantly different between the SSNS and SRNS groups. There were also no significant differences between groups for risk of obesity (RR 2.53; 95%CI 0.58 to 10.99 or central obesity (RR 1.39; 95%CI 0.45 to 4.25. Conclusion In children with nephrotic syndrome who received corticosteroids, the prevalence of obesity is 22% and of central obesity is 50%. In a comparison of SSNS and SRNS groups, cumulative steroid dose as well as risks of obesity and central obesity do not significantly differ between groups.

  6. A Pilot Study of IL2 in Drug-Resistant Idiopathic Nephrotic Syndrome.

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    Alice Bonanni

    Full Text Available Tregs infusion reverts proteinuria and reduces renal lesions in most animal models of nephrotic syndrome (i.e. Buffalo/Mna, Adriamycin, Promycin, LPS. IL2 up-regulates Tregs and may be an alternative to cell-therapy in this setting. To evaluate a potential role of IL2 as Tregs inducer and proteinuria lowering agent in human nephrotic syndrome we treated 5 nephrotic patients with 6 monthly cycles of low-dose IL2 (1x106 U/m2 first month, 1.5x106 U/m2 following months. The study cohort consisted of 5 children (all boys, 11–17 years resistant to all the available treatments (i.e. steroids, calcineurin inhibitors, mycophenolate, Rituximab. Participants had Focal Segmental Glomerulosclerosis (3 cases or Minimal Change Nephropathy (2 cases. IL2 was safe in all but one patient who had an acute asthma attack after the first IL2 dose and did not receive further doses. Circulating Tregs were stably increased (>10% during the whole study period in 2 cases while were only partially modified in the other two children who started with very low levels and partially responded to single IL2 Proteinuria and renal function were not modified by IL2 at any phase of the study. We concluded that low-dose IL2 given in monthly pulses is safe and modifies the levels of circulating Tregs. This drug may not be able to lower proteinuria or affect renal function in children with idiopathic nephrotic syndrome. We were unable to reproduce in humans the effects of IL2 described in rats and mice reducing de facto the interest on this drug in nephrotic syndrome.ClinicalTrials.gov NCT02455908.

  7. Experience with second line drugs in frequently relapsing and steroid dependent childhood nephrotic syndrome in a large Saudi center

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    Khalid Alsaran, M.D.

    2017-06-01

    Conclusion: All the second line drugs in our study were equally effective. However, we recommend that the initial treatment of FR/SD nephrotic syndrome should be chosen with the least toxic yet equally efficacious drug Levamisole.

  8. Late Onset Cobalamin Disorder and Hemolytic Uremic Syndrome: A Rare Cause of Nephrotic Syndrome

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    Gianluigi Ardissino

    2017-01-01

    Full Text Available Hemolytic uremic syndrome (HUS is an unrare and severe thrombotic microangiopathy (TMA caused by several pathogenetic mechanisms among which Shiga toxin-producing Escherichia coli infections and complement dysregulation are the most common. However, very rarely and particularly in neonates and infants, disorders of cobalamin metabolism (CblC can present with or be complicated by TMA. Herein we describe a case of atypical HUS (aHUS related to CblC disease which first presented in a previously healthy boy at age of 13.6 years. The clinical picture was initially dominated by nephrotic range proteinuria and severe hypertension followed by renal failure. The specific treatment with high dose of hydroxycobalamin rapidly obtained the remission of TMA and the complete recovery of renal function. We conclude that plasma homocysteine and methionine determinations together with urine organic acid analysis should be included in the diagnostic work-up of any patient with TMA and/or nephrotic syndrome regardless of age.

  9. Up-regulation of hepatic Acyl CoA: Diacylglycerol acyltransferase-1 (DGAT-1) expression in nephrotic syndrome.

    Science.gov (United States)

    Vaziri, Nosratola D; Kim, Choong H; Phan, Dennis; Kim, Sara; Liang, Kaihui

    2004-07-01

    Nephrotic syndrome is associated with hypercholesterolemia, hypertriglyceridemia, and marked elevations of plasma low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL). Hypertriglyceridemia in nephrotic syndrome is accompanied by increased hepatic fatty acid synthesis, elevated triglyceride secretion, as well as lipoprotein lipase, VLDL-receptor, and hepatic triglyceride lipase deficiencies, which lead to impaired clearance of triglyceride-rich lipoproteins. Acyl CoA: diacylglycerol acyltransferase (DGAT) is a microsomal enzyme that joins acyl CoA to 1, 2-diacylglycerol to form triglyceride. Two distinct DGATs (DGAT-1 and DGAT2) have recently been identified in the liver and other tissues. The present study tested the hypothesis that the reported increase in hepatic triglyceride secretion in nephrotic syndrome may be caused by up-regulation of DGAT. Male Sprague-Dawley rats were rendered nephrotic by two sequential injections of puromycin aminonucleoside (130 mg/kg on day 1 and 60 mg/kg on day 14) and studied on day 30. Placebo-treated rats served as controls. Hepatic DGAT-1 and DGAT-2 mRNA abundance and enzymatic activity were measured. The nephrotic group exhibited heavy proteinuria, hypoalbuminemia, hypercholesterolemia, hypertriglyceridemia, and marked elevation of VLDL concentration. Hepatic DGAT-1 mRNA, DGAT-1, and total DGAT activity were significantly increased, whereas DGAT-2 mRNA abundance and activity were unchanged in the nephrotic rats compared to the control animals. The functional significance of elevation of DGAT activity was illustrated by the reduction in microsomal free fatty acid concentration in the liver of nephrotic animals. Nephrotic syndrome results in up-regulation of hepatic DGAT-1 expression and activity, which can potentially contribute to the associated hypertriglyceridemia by enhancing triglyceride synthesis. Thus, it appears that both depressed catabolism and increased synthetic capacity contribute to

  10. A RETROSPECTIVE STUDY ON CLINICAL PRESENTATION OF STEROID SENSITIVE NEPHROTIC SYNDROME

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    Sosamma M. M

    2016-09-01

    Full Text Available BACKGROUND Nephrotic syndrome is a disease affecting the renal system. Most paediatricians will invariably encounter children with nephrotic syndrome in their clinic. The disease is characterised by the presence of oedema, persistent heavy proteinuria, hypoproteinaemia and hypercholesterolaemia. The disease is influenced by factors like age, geography, race and also has certain genetic influence related to HLA (DR7, B12, B8. In children, minimal change nephrotic syndrome is the most common variant of primary nephrotic syndrome. It accounts to more than eighty per cent of the cases seen children under seven years whereas it has a chance of fifty per cent in the age group of seven to sixteen years. Males are affected two times higher compared to females. The parents usually bring the child to the hospital with signs of oedema. Usually, the child recovers with treatment, but in some cases, there can be relapse. MATERIALS AND METHODS  The study was conducted in the Department of Paediatrics, Travancore Medical College, Kollam.  The study was done from January 2015 to January 2016.  Sixty cases were identified and were chosen for the study. INCLUSION CRITERIA 1. Steroid sensitive cases of nephrotic syndrome. 2. Age less than twelve years. 3. Admitted cases. EXCLUSION CRITERIA 1. Steroid-resistant and steroid-dependent cases. 2. Age more than twelve years. 3. Outpatient cases. RESULTS Out of the sixty cases studied, forty one cases belonged to male sex and nineteen cases belonged to female sex. Based on the age group, maximum number of cases belonged to age group four to eight years, which amounted to thirty four cases followed by age group eight to twelve years, which amounted to eighteen cases. Age group zero to four years had the least number of cases, which amounted to eight in number. Based on clinical signs and symptoms, fifty five cases presented with oedema either periorbital, scrotal or pedal oedema. Ten cases presented with fever

  11. Kinetics of Rituximab Excretion into Urine and Peritoneal Fluid in Two Patients with Nephrotic Syndrome

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    Klaus Stahl

    2017-01-01

    Full Text Available Clinical observations suggest that treatment of Rituximab might be less effective in patients with nephrotic range proteinuria when compared to nonnephrotic patients. It is conceivable that the reason for this is that significant amounts of Rituximab might be lost in the urine in a nephrotic patient and that these patients require a repeated or higher dosage. However, this has not been systematically studied. In this case report we describe two different patients with nephrotic range proteinuria receiving Rituximab. The first patient received Rituximab for therapy resistant cryoglobulinemic membranoproliferative glomerulonephritis and the other for second line treatment of Felty’s syndrome. We employed flow cytometry to determine the amount of Rituximab excretion in both urine and peritoneal fluid specimens in these patients following administration of Rituximab. We found that a significant amount of Rituximab is lost from the circulation by excretion into the urine. Furthermore we saw a close correlation of the excretion of Rituximab to the excretion of IgG molecules suggesting selectivity of proteinuria as the determining factor of Rituximab excretion. Further larger scale clinical studies could have the potential to evaluate an optimal cut-off value of IgG urinary loss before a possible administration of Rituximab therefore contributing to a more individualized treatment approach in patients with nonselective and nephrotic range proteinuria.

  12. Kinetics of Rituximab Excretion into Urine and Peritoneal Fluid in Two Patients with Nephrotic Syndrome.

    Science.gov (United States)

    Stahl, Klaus; Duong, Michelle; Schwarz, Anke; Wagner, A D; Haller, Hermann; Schiffer, Mario; Jacobs, Roland

    2017-01-01

    Clinical observations suggest that treatment of Rituximab might be less effective in patients with nephrotic range proteinuria when compared to nonnephrotic patients. It is conceivable that the reason for this is that significant amounts of Rituximab might be lost in the urine in a nephrotic patient and that these patients require a repeated or higher dosage. However, this has not been systematically studied. In this case report we describe two different patients with nephrotic range proteinuria receiving Rituximab. The first patient received Rituximab for therapy resistant cryoglobulinemic membranoproliferative glomerulonephritis and the other for second line treatment of Felty's syndrome. We employed flow cytometry to determine the amount of Rituximab excretion in both urine and peritoneal fluid specimens in these patients following administration of Rituximab. We found that a significant amount of Rituximab is lost from the circulation by excretion into the urine. Furthermore we saw a close correlation of the excretion of Rituximab to the excretion of IgG molecules suggesting selectivity of proteinuria as the determining factor of Rituximab excretion. Further larger scale clinical studies could have the potential to evaluate an optimal cut-off value of IgG urinary loss before a possible administration of Rituximab therefore contributing to a more individualized treatment approach in patients with nonselective and nephrotic range proteinuria.

  13. Anakinra induces complete remission of nephrotic syndrome in a patient with familial mediterranean fever and amyloidosis.

    Science.gov (United States)

    Sevillano, Ángel M; Hernandez, Eduardo; Gonzalez, Esther; Mateo, Isabel; Gutierrez, Eduardo; Morales, Enrique; Praga, Manuel

    2016-01-01

    Renal amyloidosis is one of the most severe complications of familial Mediterranean fever (FMF). Colchicine has reduced the incidence of this complication, which now only appears in untreated, under-treated and resistant patients, but it is usually ineffective in patients with advanced amyloidosis. Here we report a patient with FMF and biopsy-proven amyloidosis who presented with nephrotic syndrome despite colchicine treatment. Anakinra (an interleukin-1β inhibitor) was started and a dramatic complete remission of nephrotic syndrome was observed in the following months. Anakinra can be an effective treatment for FMF patients with severe secondary amyloidosis. Copyright © 2015 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Mesangioproliferative glomerulonephritis in a patient with Kimura′s disease presenting as Nephrotic syndrome

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    Surendra Singh Rathore

    2015-01-01

    Full Text Available Kimura′s disease is a rare chronic eosinophilic inflammatory disorder of unknown etiology. Majority of cases have been reported from South East Asia, while sporadic occurrences have been reported worldwide, including the Indian subcontinent. Nephrotic syndrome may be the presenting manifestation of Kimura′s disease, and a variety of renal lesions are observed histologically in such patients. We herein describe a case of steroid-responsive mesangioproliferative glomerulonephritis related to kimura′s disease.

  15. Mycophenolic Acid Pharmacokinetics and Relapse in Children with Steroid–Dependent Idiopathic Nephrotic Syndrome

    Science.gov (United States)

    Tellier, Stéphanie; Dallocchio, Aymeric; Guigonis, Vincent; Saint-Marcoux, Frank; Llanas, Brigitte; Ichay, Lydia; Bandin, Flavio; Godron, Astrid; Morin, Denis; Brochard, Karine; Gandia, Peggy; Bouchet, Stéphane; Marquet, Pierre; Decramer, Stéphane

    2016-01-01

    Background and objectives Therapeutic drug monitoring of mycophenolic acid can improve clinical outcome in organ transplantation and lupus, but data are scarce in idiopathic nephrotic syndrome. The aim of our study was to investigate whether mycophenolic acid pharmacokinetics are associated with disease control in children receiving mycophenolate mofetil for the treatment of steroid–dependent nephrotic syndrome. Design, setting, participants, & measurements This was a retrospective multicenter study including 95 children with steroid–dependent nephrotic syndrome treated with mycophenolate mofetil with or without steroids. Area under the concentration-time curve of mycophenolic acid was determined in all children on the basis of sampling times at 20, 60, and 180 minutes postdose, using Bayesian estimation. The association between a threshold value of the area under the concentration-time curve of mycophenolic acid and the relapse rate was assessed using a negative binomial model. Results In total, 140 areas under the concentration-time curve of mycophenolic acid were analyzed. The findings indicate individual dose adaptation in 53 patients (38%) to achieve an area under the concentration-time curve target of 30–60 mg·h/L. In a multivariable negative binomial model including sex, age at disease onset, time to start of mycophenolate mofetil, previous immunomodulatory treatment, and concomitant prednisone dose, a level of area under the concentration-time curve of mycophenolic acid >45 mg·h/L was significantly associated with a lower relapse rate (rate ratio, 0.65; 95% confidence interval, 0.46 to 0.89; P=0.01). Conclusions Therapeutic drug monitoring leading to individualized dosing may improve the efficacy of mycophenolate mofetil in steroid–dependent nephrotic syndrome. Additional prospective studies are warranted to determine the optimal target for area under the concentration-time curve of mycophenolic acid in this population. PMID:27445161

  16. Daily corticosteroids reduce infection-associated relapses in frequently relapsing nephrotic syndrome: a randomized controlled trial.

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    Gulati, Ashima; Sinha, Aditi; Sreenivas, Vishnubhatla; Math, Aparna; Hari, Pankaj; Bagga, Arvind

    2011-01-01

    Relapses of nephrotic syndrome often follow minor infections, commonly of the upper respiratory tract. Daily administration of maintenance prednisolone during intercurrent infections was examined to determine whether the treatment reduces relapse rates in children with frequently relapsing nephrotic syndrome. In a randomized controlled trial (nonblind, parallel group, tertiary-care hospital), 100 patients with idiopathic, frequently relapsing nephrotic syndrome eligible for therapy with prolonged low-dose, alternate-day prednisolone with or without levamisole were randomized to either receive their usual dose of alternate-day prednisolone daily for 7 days during intercurrent infections (intervention group) or continue alternate-day prednisolone (controls). Primary outcome was assessed by comparing the rates of infection-associated relapses at 12-month follow-up. Secondary outcomes were the frequency of infections and the cumulative amount of prednisolone received in both groups. Patients in the intervention group showed significantly lower infection-associated (rate difference, 0.7 episodes/patient per year; 95% confidence intervals [CI] 0.3, 1.1) and lower total relapse rates (0.9 episodes/patient per year, 95% CI 0.4, 1.4) without increase in steroid toxicity. Poisson regression, adjusted for occurrence of infections, showed that daily administration of prednisolone during infections independently resulted in 59% reduction in frequency of relapses (rate ratio, 0.41; 95% CI 0.3, 0.6). For every six patients receiving this intervention, one showed a reduction of relapse frequency to less than three per year. Daily administration of maintenance doses of prednisolone, during intercurrent infections, significantly reduces relapse rates and the proportion of children with frequently relapsing nephrotic syndrome.

  17. Management of steroid resistant nephrotic syndrome in children with cyclosporine - a tertiary care centre experience

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    Shah, S.S.H.; Akhtar, N.; Sunbleen, F.

    2015-01-01

    Objective: To observe the response and adverse effects of cyclosporine in combination with oral steroids for management of idiopathic steroid resistant nephrotic syndrome in pediatric patients. Methodology: It was an observational study conducted at Children Hospital, Lahore, Pakistan from March 2014 to June 2015. Forty normotensive patients of idiopathic steroid resistant nephrotic syndrome between one and twelve years of age with normal renal function were included in the study. Patients were prescribed cyclosporine with prednisolone and were followed to see the response and adverse effects of drugs. Results: Out of 40 patients, 20(50%) were males and 20(50%) females. Mesangioproliferative glomerulonephritis was found in 27(67.5%) patients followed by Focal segmental glomerulosclerosis in 9(22.5%) patients. Complete response was observed in 32(80%) children while partial response in 8(20%) patients at the end of six months. The most common adverse effects were cushingoid features seen in 26(65%) and cyclosporine related hypertrichosis in 34(85%). Conclusion: Management of idiopathic steroid resistant nephrotic syndrome in children with a combination of cyclosporine and prednisolone provided good results as response to treatment was seen in 80% patients. (author)

  18. Neuromyelitis optica accompanied by nephrotic syndrome and autoimmune-related pancytopenia.

    Science.gov (United States)

    ZhangBao, Jingzi; Zhou, Lei; Lu, Jiahong; Xi, Jianying; Zhao, Chongbo; Quan, Chao

    2016-05-01

    Neuromyelitis optica (NMO) associated with nephrotic syndrome and autoimmune-related pancytopenia has not been reported previously. We report herein a young woman who initially presented with bilateral blurring of vision and numbness in her hands. MRI disclosed multiple white matter lesions and a long cervical spinal cord lesion extending to the medulla oblongata. Serum aquaporin-4 antibody was positive and the patient was diagnosed with NMO. While in the hospital, she presented with hypoproteinemia and heavy proteinuria, meeting the diagnostic criteria of nephrotic syndrome. After high-dose methylprednisolone treatment, her vision improved significantly and urine protein quantity decreased. However, the patient subsequently developed severe pancytopenia with a positive Coombs' test. Thrombocytopenia finally led to uncontrollable gastrointestinal bleeding as the direct cause of the patient's death. This case illustrates the extremely rare condition of concurrence of NMO, nephrotic syndrome, and autoimmune pancytopenia in one patient, which suggests the involvement of organs beyond the central nervous system in NMO spectrum disorders. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Management of Diabetes Associated with Nephrotic Syndrome: Therapeutic Potential of Dapagliflozin for Protracted Volume Retention

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    Toshimi Imai

    2015-01-01

    Full Text Available A 48-year-old female was admitted to our hospital presenting with a chief complaint of progressive swelling because of diabetic nephrotic syndrome. Dapagliflozin seemed to play a role in accelerating the patient's urinary sodium excretion as well as reducing gross fluid retention despite the fact that her nephrotic condition was resistant to furosemide. Our experience emphasizes a potential novel approach to overcoming loop diuretic resistance using this agent among some subsets of type 2 diabetic subjects complicated with severe volume accumulation. We believe that combination treatment consisting of dapagliflozin and furosemide may produce diuretic synergy via sequential nephron blockade. The accumulation of more experience with additional cases similar to ours requires continuous and careful attention.

  20. Rituximab for childhood-onset, complicated, frequently relapsing nephrotic syndrome or steroid-dependent nephrotic syndrome: a multicentre, double-blind, randomised, placebo-controlled trial.

    Science.gov (United States)

    Iijima, Kazumoto; Sako, Mayumi; Nozu, Kandai; Mori, Rintaro; Tuchida, Nao; Kamei, Koichi; Miura, Kenichiro; Aya, Kunihiko; Nakanishi, Koichi; Ohtomo, Yoshiyuki; Takahashi, Shori; Tanaka, Ryojiro; Kaito, Hiroshi; Nakamura, Hidefumi; Ishikura, Kenji; Ito, Shuichi; Ohashi, Yasuo

    2014-10-04

    Rituximab could be an effective treatment for childhood-onset, complicated, frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS). We investigated the efficacy and safety of rituximab in patients with high disease activity. We did a multicentre, double-blind, randomised, placebo-controlled trial at nine centres in Japan. We screened patients aged 2 years or older experiencing a relapse of FRNS or SDNS, which had originally been diagnosed as nephrotic syndrome when aged 1-18 years. Patients with complicated FRNS or SDNS who met all other criteria were eligible for inclusion after remission of the relapse at screening. We used a computer-generated sequence to randomly assign patients (1:1) to receive rituximab (375 mg/m(2)) or placebo once weekly for 4 weeks, with age, institution, treatment history, and the intervals between the previous three relapses as adjustment factors. Patients, guardians, caregivers, physicians, and individuals assessing outcomes were masked to assignments. All patients received standard steroid treatment for the relapse at screening and stopped taking immunosuppressive agents by 169 days after randomisation. Patients were followed up for 1 year. The primary endpoint was the relapse-free period. Safety endpoints were frequency and severity of adverse events. Patients who received their assigned intervention were included in analyses. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000001405. Patients were centrally registered between Nov 13, 2008, and May 19, 2010. Of 52 patients who underwent randomisation, 48 received the assigned intervention (24 were given rituximab and 24 placebo). The median relapse-free period was significantly longer in the rituximab group (267 days, 95% CI 223-374) than in the placebo group (101 days, 70-155; hazard ratio: 0·27, 0·14-0·53; p<0·0001). Ten patients (42%) in the rituximab group and six (25

  1. Congenital nephrotic syndrome may respond to cyclosporine A: A case report and review of literature

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    Mulić Bilsana

    2017-01-01

    Full Text Available Introduction. Congenital nephrotic syndrome (CNF is manifested at birth or within the first three months of life. The Finnish-type of CNF is caused by the mutation of the NPHS1 gene, which encodes nephrin in the podocyte slit diaphragm. It is a very severe disease, for which immunosuppressive therapy is not advised. Here we describe a patient with CNF who responded to CsA by partial remission. Case outline. A girl aged 2.5 months presented with severe non-syndromic steroid-resistant nephrotic syndrome. She needed aggressive support including daily albumin infusions and diuretics. Substitution of vitamin D, thyroxin, and anticoagulants were regularly administered. She was also treated with angiotensin converting enzyme inhibitor, without clear benefits regarding proteinuria. In addition, she received intravenous gamma-globulin replacement therapy and antibiotics during frequent infections. While waiting for the results of genetic analyses and faced with many problems related to daily albumin infusions, infections, and thromboembolic complications, cyclosporine A (CsA was introduced as an alternative to early nephrectomy and consequent renal failure. The patient responded by partial remission and CsA treatment continued at home without the albumin infusions. After almost five years since the beginning of the treatment, the patient’s renal function remains unreduced. Conclusion. Our case demonstrates that CsA can induce partial remission in patients with genetic forms of steroid-resistant nephrotic syndrome without influencing the glomerular filtration rate. However, its long-term effect and safety should carefully be monitored. [Project of the Ministry of Education, Science and Technological Development of Republic of Serbia, Grant No. 175079

  2. A Novel Biomarker Panel to Identify Steroid Resistance in Childhood Idiopathic Nephrotic Syndrome

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    Michael R Bennett

    2017-03-01

    Full Text Available Idiopathic nephrotic syndrome (NS is the most common glomerular disorder of childhood. Response to initial treatment with corticosteroids is an indicator of prognosis, as resistant patients often present more progressive disease. In this cross-sectional pilot study, we set out to discover a panel of noninvasive biomarkers that could distinguish steroid-resistant nephrotic syndrome (SRNS from steroid-sensitive nephrotic syndrome (SSNS. Information gleaned from such a panel could yield more individualized treatment plans and prevent unnecessary steroid exposure in patients unlikely to respond. Urine was collected from 50 pediatric patients diagnosed with idiopathic NS at Cincinnati Children’s Hospital Medical Center. Isobaric tags for relative and absolute quantitation (iTRAQ was used to discover 13 proteins that were differentially expressed in SSNS vs SRNS in a small 5 × 5 discovery cohort. Suitable assays were found for 9 of the 13 markers identified by iTRAQ and were used in a 25 SRNS × 25 SSNS validation cohort. Vitamin D–binding protein (VDBP, alpha-1 acid glycoprotein 1 (AGP1, alpha-1 acid glycoprotein 2 (AGP2, alpha-1-B glycoprotein (A1BG, fetuin-A, prealbumin, thyroxine-binding globulin and hemopexin, and alpha-2 macroglobulin were measured and combined with urine neutrophil gelatinase–associated lipocalin (NGAL, which had been previously shown to distinguish patients with SRNS. Urinary VDBP, prealbumin, NGAL, fetuin-A, and AGP2 were found to be significantly elevated in SRNS using univariate analysis, with area under the receiver operating characteristic curves (AUCs ranging from 0.65 to 0.81. Multivariate analysis revealed a panel of all 10 markers that yielded an AUC of 0.92 for identification of SRNS. A subset of 5 markers (including VDBP, NGAL, fetuin-A, prealbumin, and AGP2 showed significant associations with SRNS and yielded an AUC of 0.85.

  3. Nephrotic syndrome in primary myelofibrosis with renal extramedullary hematopoiesis and glomerulopathy in the JAK inhibitor era.

    Science.gov (United States)

    Del Sordo, Rachele; Brugnano, Rachele; Covarelli, Carla; Fiorucci, Gioia; Falzetti, Franca; Barbatelli, Giorgio; Nunzi, Emidio; Sidoni, Angelo

    2017-01-01

    Primary myelofibrosis (PMF) is an uncommon form of myeloproliferative neoplasm (MPN) characterized by a proliferation of predominantly megakaryocytes and granulocytes in the bone marrow that, in fully-developed disease, is associated with reactive deposition of fibrous connective tissue, extramedullary hematopoiesis (EMH), and splenomegaly. Kidney involvement is rare and clinically presents with proteinuria, nephrotic syndrome, and renal insufficiency. Renal damage can be due to EMH and glomerulopathy. Renal EMH presents three patterns: infiltration of the interstitium with possible renal failure caused by functional damage of parenchyma and vessels, infiltration of capsule and pericapsular adipose tissue, and sclerosing mass-like lesions that can cause hydronephrosis and hydroureter with obstructive uropathy and renal failure. Glomerulopathy associated with PMF is rarely described, ranging from 1 month to 18 years from diagnosis of the neoplasm to renal biopsy. It is characterized by expansion and hypercellularity mesangial, segmental sclerosis, features of chronic thrombotic microangiopathy (TMA), and intracapillary hematopoietic cells infiltrating in absence of immune-mediated glomerulonephritis. We present a nephrotic syndrome in PMF-related glomerulopathy, associated with EMH, without renal failure, in a patient under treatment for 2 years with JAK2 inhibitor ruxolitinib. Despite treatment, the patient died 7 months after renal biopsy. Nephrologists still know very little about this topic and there is no homogeneous data about incidence, pathogenesis, and optimal treatment of this poor prognostic PMF-associated nephrotic syndrome. We focus on data in the literature in the hope of stimulating hematologists, nephrologists, pathologists to future studies about the natural history of renal involvement, useful for optimal management of this rare pathology.

  4. Plasma homocysteine and B vitamins levels in Nigerian children with nephrotic syndrome.

    Science.gov (United States)

    Orimadegun, Bose Etaniamhe; Orimadegun, Adebola Emmanuel; Ademola, Adebowale Dele; Agbedana, Emmanuel Oluyemi

    2014-01-01

    Available data on plasma homocysteine level in patients with nephrotic syndrome (NS) are controversial with increased, decreased and unchanged values reported. Therefore, plasma homocysteine and serum B vitamins in Nigerian children with NS were assessed in this study. Fasting blood samples were analysed for plasma homocysteine, serum folate and B vitamins in 42 children with NS and 42 age and sex-matched healthy controls in this case control study. Data were compared between NS and control using t test and Chi square. Relationships were tested with regression analysis with p set at 0.05. Prevalence of hyperhomocysteinaemia, low folate and cyanocobalamin in NS was 57.1%, 14.3% and 9.5% respectively. The mean homocysteine level was significantly higher in NS than control (11.3±2.6 µmol/L versus 5.5±2.3 µmol/L). Also, NS had lower folate and cyanocobalamin than control: 9.1±3.9 ng/mL versus 11.2±3.1 ng/dL and 268.5±95.7 pg/mL versus 316±117.2 pg/mL respectively. Weak but significant correlation between homocysteine and serum albumin (r = 0.347), folate (r = -0.607) and vitamin B12 (r = -0.185) were found in the NS group. Significant relationship was also found between homocysteine and vitamin B12 (ß = -0.64, 95% CI = -1.20, -0.08) after controlling for folate and vitamin B6 levels. Clinically important hyperhomocysteinaemia and low B vitamins occur in Nigerian children with nephrotic syndrome. This data suggest that potential usefulness of folate and vitamin B supplementation for reducing high homocysteine levels in nephrotic syndrome need to be further investigated.

  5. Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort.

    Science.gov (United States)

    Trautmann, Agnes; Bodria, Monica; Ozaltin, Fatih; Gheisari, Alaleh; Melk, Anette; Azocar, Marta; Anarat, Ali; Caliskan, Salim; Emma, Francesco; Gellermann, Jutta; Oh, Jun; Baskin, Esra; Ksiazek, Joanna; Remuzzi, Giuseppe; Erdogan, Ozlem; Akman, Sema; Dusek, Jiri; Davitaia, Tinatin; Özkaya, Ozan; Papachristou, Fotios; Firszt-Adamczyk, Agnieszka; Urasinski, Tomasz; Testa, Sara; Krmar, Rafael T; Hyla-Klekot, Lidia; Pasini, Andrea; Özcakar, Z Birsin; Sallay, Peter; Cakar, Nilgun; Galanti, Monica; Terzic, Joelle; Aoun, Bilal; Caldas Afonso, Alberto; Szymanik-Grzelak, Hanna; Lipska, Beata S; Schnaidt, Sven; Schaefer, Franz

    2015-04-07

    Steroid-resistant nephrotic syndrome is a rare kidney disease involving either immune-mediated or genetic alterations of podocyte structure and function. The rare nature, heterogeneity, and slow evolution of the disorder are major obstacles to systematic genotype-phenotype, intervention, and outcome studies, hampering the development of evidence-based diagnostic and therapeutic concepts. To overcome these limitations, the PodoNet Consortium has created an international registry for congenital nephrotic syndrome and childhood-onset steroid-resistant nephrotic syndrome. Since August of 2009, clinical, biochemical, genetic, and histopathologic information was collected both retrospectively and prospectively from 1655 patients with childhood-onset steroid-resistant nephrotic syndrome, congenital nephrotic syndrome, or persistent subnephrotic proteinuria of likely genetic origin at 67 centers in 21 countries through an online portal. Steroid-resistant nephrotic syndrome manifested in the first 5 years of life in 64% of the patients. Congenital nephrotic syndrome accounted for 6% of all patients. Extrarenal abnormalities were reported in 17% of patients. The most common histopathologic diagnoses were FSGS (56%), minimal change nephropathy (21%), and mesangioproliferative GN (12%). Mutation screening was performed in 1174 patients, and a genetic disease cause was identified in 23.6% of the screened patients. Among 14 genes with reported mutations, abnormalities in NPHS2 (n=138), WT1 (n=48), and NPHS1 (n=41) were most commonly identified. The proportion of patients with a genetic disease cause decreased with increasing manifestation age: from 66% in congenital nephrotic syndrome to 15%-16% in schoolchildren and adolescents. Among various intensified immunosuppressive therapy protocols, calcineurin inhibitors and rituximab yielded consistently high response rates, with 40%-45% of patients achieving complete remission. Confirmation of a genetic diagnosis but not the

  6. The Evidence-Based Approach to Adult-Onset Idiopathic Nephrotic Syndrome.

    Science.gov (United States)

    Canetta, Pietro A A; Radhakrishnan, Jai

    2015-01-01

    Adult-onset nephrotic syndrome (NS) differs from its pediatric counterpart in several important ways. Most importantly, NS in adults is more etiologically heterogeneous compared to children, and thus treatment approaches rely heavily on the histological diagnosis provided by renal biopsy. The evidence-based approach to treatment of adult NS has been critically examined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines in glomerulonephritis, published in 2012. Here, we examine the strengths and limits of those guidelines and review recent work that expands the evidence-based approach.

  7. Generalised pustular psoriasis, psoriatic arthritis and nephrotic syndrome associated with systemic amyloidosis.

    Science.gov (United States)

    David, M; Abraham, D; Weinberger, A; Feuerman, E J

    1982-09-01

    The case report is presented of a psoriatic patient with arthropathy, generalised pustular psoriasis and nephrotic syndrome, in whom systemic amyloidosis developed. The literature reports 13 cases of psoriasis associated with amyloidosis, 3 of whom suffered from pustular psoriasis as does our case. With the addition of our case, 12 of these 14 had concomitant arthropathy. This seems to suggest that arthritis is an important factor in the appearance of amyloidosis. Rectal biopsy and/or renal biopsy may be helpful in establishing the diagnosis of amyloidosis relatively early in patients with psoriatic arthritis.

  8. Giant Cell Arteritis in a 12-Year-Old Girl Presenting with Nephrotic Syndrome

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    Zeinab A. El-Sayed

    2014-01-01

    Full Text Available Giant cell arteritis (GCA is rare in children. The kidneys are generally spared. We present a case of GCA in a 12-year-old girl with severe headache and tender scalp especially over the right temporal area. The right superficial temporal artery was cord like and nodular and the pulsations were barely felt. Several small tender nodular swellings were felt in the occipital area. She had been previously diagnosed as a case of nephrotic syndrome due to underlying membranoproliferative glomerulonephritis. This report is aimed at drawing attention to this rare form of vasculitis in children aiming at decreasing its morbidities.

  9. Urinary potassium to urinary potassium plus sodium ratio can accurately identify hypovolemia in nephrotic syndrome: a provisional study.

    Science.gov (United States)

    Keenswijk, Werner; Ilias, Mohamad Ikram; Raes, Ann; Donckerwolcke, Raymond; Walle, Johan Vande

    2018-01-01

    There is evidence pointing to a decrease of the glomerular filtration rate (GFR) in a subgroup of nephrotic children, likely secondary to hypovolemia. The aim of this study is to validate the use of urinary potassium to the sum of potassium plus sodium ratio (UK/UK+UNa) as an indicator of hypovolemia in nephrotic syndrome, enabling detection of those patients who will benefit from albumin infusion. We prospectively studied 44 nephrotic children and compared different parameters to a control group (36 children). Renal perfusion and glomerular permeability were assessed by measuring clearance of para-aminohippurate and inulin. Vaso-active hormones and urinary sodium and potassium were also measured. Subjects were grouped into low, normal, and high GFR groups. In the low GFR group, significantly lower renal plasma flow (p = 0.01), filtration fraction (p = 0.01), and higher UK/UK+UNa (p = 0.03) ratio were noted. In addition, non-significant higher plasma renin activity (p = 0.11) and aldosteron (p = 0.09) were also seen in the low GFR group. A subgroup of patients in nephrotic syndrome has a decrease in glomerular filtration, apparently related to hypovolemia which likely can be detected by a urinary potassium to potassium plus sodium ratio > 0.5-0.6 suggesting benefit of albumin infusion in this subgroup. What is Known: • Volume status can be difficult to assess based on clinical parameters in nephrotic syndrome, and albumin infusion can be associated with development of pulmonary edema and fluid overload in these patients. What is New: • Urinary potassium to the sum of urinary potassium plus sodium ratio can accurately detect hypovolemia in nephrotic syndrome and thus identify those children who would probably respond to albumin infusion.

  10. Relapse of nephrotic syndrome during post-rituximab peripheral blood B-lymphocyte depletion.

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    Sato, Mai; Kamei, Koichi; Ogura, Masao; Ishikura, Kenji; Ito, Shuichi

    2018-02-01

    Rituximab is effective against complicated childhood steroid-dependent nephrotic syndrome (SDNS). Peripheral blood B-lymphocyte (B-cell) depletion is strongly correlated with persistent remission, relapse rarely occurring during B-cell depletion; however, we have encountered several such patients. We retrospectively analyzed the characteristics and clinical course of 82 patients with SDNS treated with rituximab from January 2007 to December 2012 in our institution. Six of 82 patients (7.3%) had relapses during B-cell depletion after receiving rituximab (relapsed group). The remaining 76 patients did not have relapses during B-cell depletion (non-relapsed group). The median time to initial relapse during B-cell depletion was 85 days after receiving rituximab, which is significantly shorter than in the non-relapsed group (410 days, p = 0.0003). The median annual numbers of relapses after receiving rituximab were 2.5 and 0.9 in the relapsed and non-relapsed groups, respectively (p depletion did not differ between the two groups. Relapse during B-cell depletion after receiving rituximab suggests that various pathophysiological mechanisms play a part in childhood nephrotic syndrome.

  11. Long-Term Outcome of Steroid-Resistant Nephrotic Syndrome in Children.

    Science.gov (United States)

    Trautmann, Agnes; Schnaidt, Sven; Lipska-Ziętkiewicz, Beata S; Bodria, Monica; Ozaltin, Fatih; Emma, Francesco; Anarat, Ali; Melk, Anette; Azocar, Marta; Oh, Jun; Saeed, Bassam; Gheisari, Alaleh; Caliskan, Salim; Gellermann, Jutta; Higuita, Lina Maria Serna; Jankauskiene, Augustina; Drozdz, Dorota; Mir, Sevgi; Balat, Ayse; Szczepanska, Maria; Paripovic, Dusan; Zurowska, Alexandra; Bogdanovic, Radovan; Yilmaz, Alev; Ranchin, Bruno; Baskin, Esra; Erdogan, Ozlem; Remuzzi, Giuseppe; Firszt-Adamczyk, Agnieszka; Kuzma-Mroczkowska, Elzbieta; Litwin, Mieczyslaw; Murer, Luisa; Tkaczyk, Marcin; Jardim, Helena; Wasilewska, Anna; Printza, Nikoleta; Fidan, Kibriya; Simkova, Eva; Borzecka, Halina; Staude, Hagen; Hees, Katharina; Schaefer, Franz

    2017-10-01

    We investigated the value of genetic, histopathologic, and early treatment response information in prognosing long-term renal outcome in children with primary steroid-resistant nephrotic syndrome. From the PodoNet Registry, we obtained longitudinal clinical information for 1354 patients (disease onset at >3 months and children, respectively, with the highest remission rates achieved with calcineurin inhibitor-based protocols. Ten-year ESRD-free survival rates were 43%, 94%, and 72% in children with IIS resistance, complete remission, and partial remission, respectively; 27% in children with a genetic diagnosis; and 79% and 52% in children with histopathologic findings of minimal change glomerulopathy and FSGS, respectively. Five-year ESRD-free survival rate was 21% for diffuse mesangial sclerosis. IIS responsiveness, presence of a genetic diagnosis, and FSGS or diffuse mesangial sclerosis on initial biopsy as well as age, serum albumin concentration, and CKD stage at onset affected ESRD risk. Our findings suggest that responsiveness to initial IIS and detection of a hereditary podocytopathy are prognostic indicators of favorable and poor long-term outcome, respectively, in children with steroid-resistant nephrotic syndrome. Children with multidrug-resistant sporadic disease show better renal survival than those with genetic disease. Furthermore, histopathologic findings may retain prognostic relevance when a genetic diagnosis is established. Copyright © 2017 by the American Society of Nephrology.

  12. The Correlation of Regulatory T (TReg and Vitamin D3 in Pediatric Nephrotic Syndrome

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    Yunika Nurtyas

    2018-01-01

    Full Text Available Nephrotic syndrome (NS is an autoimmune disease that correlates to the imbalance of regulatory T cells (TReg. This study was aimed to investigate the effect of vitamin D as adjuvant therapy of TReg population in pediatric nephrotic syndrome. This study was designed randomized clinical trial, double blind, with pre- and post-test control groups involving 15 subjects newly diagnosed with NS. Subjects were divided into 2 groups, namely K1 for group treated with prednisone+vitamin D and K2 group for prednisone treatment only. The population of TReg in peripheral blood mononuclear cells (PBMC was analyzed using flowcytometry. Vitamin D serum level was measured through ELISA method. Results showed that there was a significant elevation of TReg (independent t-test, p = 0.010 in K1 group, which was higher than in K2 group. The Pearson test in the K1 group showed that vitamin D level was positively correlated with TReg (p = 0.039, r = 0.779.

  13. Enzymatic Activity of Candida spp. from Oral Cavity and Urine in Children with Nephrotic Syndrome.

    Science.gov (United States)

    Olczak-Kowalczyk, Dorota; Roszkowska-Blaim, Maria; Dąbkowska, Maria; Swoboda-Kopeć, Ewa; Gozdowski, Dariusz; Mizerska-Wasiak, Małgorzata; Demkow, Urszula; Pańczyk-Tomaszewska, Małgorzata

    2017-01-01

    Oral colonization with Candida spp. is not synonymous with a systemic active infection. The aim of the study was to evaluate enzymatic activity of Candida strains isolated from the oral cavity in patients with nephrotic syndrome (NS) and to compare it with the activity determined in urine. We studied 32 children with NS and 26 control healthy children. Children with NS were treated with glucocorticosteroids, cyclosporin A, mycophenolate mofetil or azathioprine. In all children, API-ZYM enzymatic tests were performed to evaluate hydrolytic enzymes of Candida isolated from the oral cavity and in urine. Candida spp. were isolated from the oral cavity in 11 patients with NS (34.4%), all receiving immunosuppressive treatment. All strains produced valine arylamidase, 9 alpha-glucosidase (E16), and 9 N-acetyl-beta-glucosaminidase (E18). A positive correlation between the presence of Candida in the oral cavity and E16 and E18 enzymatic activity in both oral cavity and urine was found. A dose of cyclosporin A had an effect on the enzymatic activity (p Candida invasion. The results of this study suggest that oral candida infection should be monitored in children with nephrotic syndrome, particularly those treated with immunosuppressive agents.

  14. Tacrolimus drug level and response to treatment in idiopathic childhood steroid resistant nephrotic syndrome

    International Nuclear Information System (INIS)

    Shah, S.S.; Hafeez, F.; Akhtar, N.

    2015-01-01

    The management of Steroid Resistant Nephrotic Syndrome (SRNS) is an uphill task for paediatric nephrologists as immunosuppressive agents are the mainstay of treatment in these patients. Tacrolimus is used along with steroids. This study is conducted to see the relationship between the tacrolimus dose, drug level and response in the management of SRNS. Methods: This quasi experimental study was conducted at The Childrens Hospital Lahore over a period of one year. Patients with SRNS of either sex and 1-10 years of age were included and those with secondary nephrotic syndrome were excluded. Tacrolimus was given at a dose of 0.05-0.1 mg/kg/day in 2 divided doses along with steroids. The follow-up was done for six months with proteinuria monitoring and tacrolimus drug levels done two weeks after initiation of treatment. Results: Out of 42 patients, 27 (64.3%) were males and 15 (35.7%) were females. The most common histological diagnosis observed was mesangio-proliferative glomerulonephritis in 30 (71.4%) patients. The tacrolimus trough level range was 0.5-15.20 ng/ml with a mean value of 4.68 ng/ml±2.85. Forty-one (97.6%) children showed complete response to treatment while one patient showed partial response. Conclusion: This study suggests that tacrolimus is an effective drug for treatment of SRNS in paediatric patients and there is no linear relationship between the drug dose, response and drug level. (author)

  15. Candida spp. and gingivitis in children with nephrotic syndrome or type 1 diabetes.

    Science.gov (United States)

    Olczak-Kowalczyk, Dorota; Pyrżak, Beata; Dąbkowska, Maria; Pańczyk-Tomaszewska, Małgorzata; Miszkurka, Grażyna; Rogozińska, Izabela; Swoboda-Kopeć, Ewa; Gozdowski, Dariusz; Kalińska, Angelika; Piróg, Anna; Mizerska-Wasiak, Małgorzata; Roszkowska-Blaim, Maria

    2015-05-08

    Diabetes and Nephrotic syndrome (NS) promote plaque-related gingivitis and yeast-like fungal infections. The study assesses the impact of Candida spp. and general disease- or treatment-related factors on plaque-related gingivitis severity in children and adolescents with Nephrotic syndrome /diabetes. Body mass index (BMI), BMI standard deviation score, and oral cavity (Plaque Index--PLI, Gingival Index--GI, mucosa status, presence and Candida enzymatic activity) were assessed in 96 patients (32 with NS: 30- immunosuppressive treatment, 35--type 1 diabetes, and 29 generally healthy), aged; 3-18 years. Laboratory included cholesterol and triglyceride measurements; in diabetic subjects- glycated haemoglobin, in NS: total protein, albumin, creatinine, haemoglobin, haematocrit, white cell count, urinary protein excretion. Medical records supplied information on disease duration and treatment. A statistical analysis was performed; Kendall Tau coefficient, chi-square test, t-test, and multiple regression analysis ( P Gingivitis occurred more frequently in patients with NS/diabetes. Gingivitis severity was correlated with PLI, age, and yeast enzyme activity in NS--to with immunosuppressive treatment with >1 drug, drug doses, treatment duration, lipid disorders, and BMI; in diabetes, with blood glucose and glycated haemoglobin >8%. Poor hygiene control is the main cause of gingivitis. Gingivitis severity is most likely related to age, lipid disorders and increase in body mass. Candida spp., in uncompensated diabetes and in those using immunosuppressive treatment, might intensify plaque-related gingivitis.

  16. Levamisole in steroid-sensitive nephrotic syndrome of childhood: the lost paradise?

    Science.gov (United States)

    Davin, J C; Merkus, M P

    2005-01-01

    Among the different drugs used for sparing steroids in steroid-sensitive nephrotic syndrome (SSNS) with frequent relapses and steroid dependency, levamisole is the least toxic and the least expensive. However, it is neither approved for this indication nor widely used in Europe. This may be explained by the difficulty in obtaining levamisole in some countries and the lack of good quality evidence for its effectiveness. Evidence is limited to three clinical trials that all suffered from methodological limitations. Statistical synthesis of these trials showed that levamisole reduces the risk of a relapse during treatment (relative risk 0.60, 95% confidence interval 0.45-0.79). From the available information, no conclusions can be drawn on the steroid-sparing effect, the long-term efficacy, and safety, as well as possible differences in efficacy in different subgroups of SSNS patients. The confirmation of a favorable effect of levamisole on the reduction of the frequency of relapses and on sparing steroids in an adequately powered, double-blind, placebo-controlled, randomized, multi-center clinical trial will promote consensus on the place of levamisole in the treatment of SSNS of childhood. Follow-up should be at least 1 year to evaluate long-term efficacy and side effects. If the results of such a clinical trial confirm the beneficial effects of levamisole in nephrotic syndrome, this may allow registration for this indication and interest companies other than Jansen-Cilag, which only recently has decided to stop its production.

  17. The correlation between attention deficit hyperactivity disorder and steroid-dependent nephrotic syndrome

    Directory of Open Access Journals (Sweden)

    Parsa Yousefichaijan

    2015-01-01

    Full Text Available Nephrotic syndrome (NS is characterized by nephritic-range proteinuria and the triad of clinical findings associated with large urinary losses of protein, hypoalbuminemia, edema and hyperlipidemia. More than 80% of children below 13 years of age with primary NS have steroid-responsive forms. There is no identifiable cause of attention-deficit hyperactivity disorder (ADHD. It is likely that the symptoms of ADHD represent a final common pathway of diverse causes, including genetic, organic and environmental etiologies. This case-control study was performed on 130 children aged between 5 and 13 years who were followed-up for two years. Sixty-five children with steroid-dependent nephrotic syndrome (SDNS as the case group and 65 healthy children as the control group were included in the study. Patients with minimal change NS were treated with prednisolone for at least six months. Conner′s Parent Rating Scale - 48 (CPRS-48 was completed by the parents and the children were identified with any form of ADHD. Then, children were referred to an expert psychiatrist. The collected data were analyzed with SPSS software. The result showed that there was no significant relationship between different types of ADHD in both groups. Thus, based on current study, one may conclude that there are no significant differences between prevalence of ADHD in children with SDNS and the control group.

  18. Long-term outcome of biopsy-proven, frequently relapsing minimal-change nephrotic syndrome in children.

    NARCIS (Netherlands)

    Kyrieleis, H.A.; Lowik, M.M.; Pronk, I.; Cruysberg, J.R.M.; Kremer, J.A.M.; Oyen, W.J.G.; Heuvel, L.P.W.J. van den; Wetzels, J.F.M.; Levtchenko, E.N.

    2009-01-01

    BACKGROUND AND OBJECTIVES: Frequently relapsing and steroid-dependent minimal-change nephrotic syndrome (MCNS) that originates in childhood can persist after puberty in >20% of patients. These patients require immunosuppressive treatment during several decades of their life. We examined long-term

  19. Minimal change nephrotic syndrome in an 82 year old patient following a tetanus-diphteria-poliomyelitis-vaccination

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    Clajus Christian

    2009-08-01

    Full Text Available Abstract Background The most common cause of idiopathic nephrotic syndrome in children and younger adults is the minimal change nephrotic syndrome (MCNS. In the elderly MCNS is relatively uncommon. Over the last decade some reports suggest a rare but possible association with the administration of various vaccines. Case presentation A 82-year old Caucasian female presented with pronounced nephrotic syndrome (proteinuria of 7.1 g/d, hypoproteinemia of 47 g/l. About six weeks prior to admission, she had received a combination vaccination for tetanus, diphtheria and poliomyelitis as a booster-vaccination from her general practitioner. The renal biopsy revealed typical minimal change lesions. She responded well to the initiated steroid treatment. As through physical examination as well as extensive laboratory and imaging studies did neither find any evidence for malignancies nor infections we suggest that the minimal change nephrotic syndrome in this patient might be related to the activation of the immune system triggered by the vaccination. Conclusion Our case as well as previous anecdotal reports suggests that vaccination and the resulting stimulations of the immune system might cause MCNS and other severe immune-reactions. Increased awareness in that regard might help to expand the database of those cases.

  20. Correlation of fractional excretion of magnesium with steroid responsiveness in children with nephrotic syndrome

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    Jubaida Rumana

    2014-01-01

    Full Text Available Steroid-resistant nephrotic syndrome (SRNS patients are candidates for other alter-native drug regimes, and the non-responsiveness to steroid is more common among glomerulo-nephritides other than minimal change disease. Without performing biopsy and proper renal histology, progression of the disease cannot be assessed. Fractional excretion of magnesium (FE Mg has been found to correlate directly with various renal histologies. The aim of this study is to evaluate the relationship of FE Mg in children with the histological pattern in SRNS. In this prospective observational study, 40 children of nephrotic syndrome, both with the first episode as well as relapse, aged 1-12 years were included in the study. Of them, 20 were steroid-responsive cases and 20 were steroid-resistant cases. FE Mg was determined in all the patients and renal histology was performed in the steroid-resistant cases. A correlation was found between FE Mg and renal histology. Data were analyzed in SPSS program version-16. Comparison of two groups was performed by the Fisher exact test and unpaired t test. P-value less than 0.05 were considered to be significant. The results of histo-pathology showed that the mean difference in FE Mg was significant (P <0.001, as FE Mg was 7.0 ± 2.3% in mesangiocapillary glomerulonephritis, 6.9 ± 1.3% in focal segmental glomerulosclerosis, 4.7 ± 0.6% in immunoglobulin M nephropathy, 4.5 ± 1.2% in focal segmental proliferative glomerulo-nephritis, 4.4 ± 1.6% in minimal change disease, 4.2 ± 0.4% in diffuse mesangial proliferative glome-rulonephritis and 3.8 ± 1.3% in mesangial proliferative glomerulonephritis. There was a statistically significant difference between FE Mg in steroid-resistant nephrotic syndrome (4.9 ± 1.9 and steroid-responsive syndrome (1.2 ± 0.3. FE Mg is a simple, minimally invasive screening marker for SRNS, and is an early predictor of clinical outcome. It can be considered as an initial investigation where biopsy

  1. Hydroxyurea for Treatment of Nephrotic Syndrome Associated With Polycythemia Vera.

    Science.gov (United States)

    Hundemer, Gregory L; Rosales, Ivy A; Chen, Yi-Bin; Colvin, Robert B; Tolkoff-Rubin, Nina E

    2016-09-01

    Myeloproliferative disorders are a rare cause of focal segmental glomerulosclerosis (FSGS), although the mechanism is unclear. Hydroxyurea is commonly used in these disorders for its cytoreductive properties; however, the effect of this treatment on proteinuria or kidney function remains unclear in cases of myeloproliferative disorder-associated FSGS. We describe the clinical course of a patient with polycythemia vera and nephrotic-range proteinuria, demonstrated to have FSGS on biopsy. The patient had a distant history of granulomatosis with polyangiitis (Wegener's), for which he routinely had his kidney function and proteinuria measured, allowing for early detection of nephrotic syndrome soon after being diagnosed with polycythemia vera. Treatment with hydroxyurea resulted in rapid improvement in proteinuria that correlated with a decrease in hematocrit. This response was replicated 2 additional times when the patient was taken off and then restarted on hydroxyurea therapy. He now maintains a steady dose of hydroxyurea with favorable kidney measures (proteinuria with <1g/d of protein excretion and serum creatinine of 1.27mg/dL [corresponding to estimated glomerular filtration rate of 56mL/min/1.73 m(2)]). This case suggests that early screening and treatment for myeloproliferative disorder-associated FSGS may lead to improved long-standing kidney function. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

  2. Primary CNS lymphoma as a cause of Korsakoff syndrome.

    Science.gov (United States)

    Toth, Cory; Voll, Chris; Macaulay, Robert

    2002-01-01

    Korsakoff syndrome presents with memory dysfunction with retrograde amnesia, anterograde amnesia, limited insight into dysfunction, and confabulation. The most common etiology of Korsakoff syndrome is thiamine deficiency secondary to alcoholism. There are limited case reports of structural lesions causing Korsakoff syndrome. A 46-year-old male with a long history of alcoholism presented with a history of confusion, amnesia, and confabulation with no localizing features on neurological examination. The patient showed no clinical change with intravenous thiamine. Computed tomography of the brain revealed a heterogenous, enhancing mass lesion centered within the third ventricle, with other lesions found throughout cortical and subcortical regions. The patient was given dexamethasone i.v. without noticeable clinical improvement but with marked radiological improvement with mass reduction. Stereotactic biopsy revealed a diagnosis of primary central nervous system (CNS) lymphoma. Most patients presenting with Korsakoff syndrome have thiamine deficiency; however, mass lesions can produce an identical clinical picture. This is the first case report of a patient with primary CNS lymphoma presenting as Korsakoff syndrome.

  3. Unusual pediatric co-morbility: autoimmune thyroiditis and cortico-resistant nephrotic syndrome in a 6-month-old Italian patient

    Directory of Open Access Journals (Sweden)

    Urbano Flavia

    2012-10-01

    Full Text Available Abstract We report on a case of autoimmune thyroiditis in a 6-month-old patient with cortico-resistant nephrotic syndrome. Normal serum levels of thyroid hormons and thyroid-stimulating hormone were detected with high titers of circulant antithyroid antibodies and a dysomogeneous ultrasound appearance of the gland, typical of autoimmune thyroiditis. The research of maternal thyroid antibodies was negative. This is the first case of autoimmune thyroiditis found in such a young patient with pre-existing nephrotic syndrome ever described in literature. This association is random because nephrotic syndrome does not have an autoimmune pathogenesis and the genes involved in autoimmune thyroiditis are not related to those of nephrotic syndrome.

  4. Albumin and Furosemide Combination for Management of Edema in Nephrotic Syndrome: A Review of Clinical Studies

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    Margaret Duffy

    2015-10-01

    Full Text Available The treatment of edema in patients with nephrotic syndrome is generally managed by dietary sodium restriction and loop diuretics. However, edema does not improve in some patients despite adequate sodium restriction and maximal dose of diuretics. In such patients, combination of albumin and a loop diuretic may improve edema by diuresis and natriuresis. The response to this combination of albumin and a diuretic has not been observed in all studies. The purpose of this review is to discuss the physiology of diuresis and natriuresis of this combination therapy, and provide a brief summary of various studies that have used albumin and a loop diuretic to improve diuretic-resistant edema. Also, the review suggests various reasons for not observing similar results by various investigators.

  5. Retroperitoneal Bleeding: An Experience During Prophylactic Anticoagulation in a Patient With Nephrotic Syndrome

    Directory of Open Access Journals (Sweden)

    Mari Okada

    2017-07-01

    Full Text Available The association between nephrotic syndrome (NS and a hypercoagulable state has been demonstrated. Controlling the blood clotting activity may therefore be attractive for patients with nephrosis in terms of thromboembolism prophylaxis. We herein report a 75-year-old woman with minimal change disease who developed pains in the right back, groin, and thigh because of retroperitoneal bleeding during prophylactic anticoagulation with unfractionated heparin. Although this procedure has not been accepted as the standard of care for patients with nephrosis, pharmacologic prophylaxis may already be practiced empirically, as in the present patient. We believe that our experience highlights the pitfalls of such a management in patients with nephrosis, implying the need for a diagnostic strategy for identifying those patients with NS who can benefit from prophylactic anticoagulation. Several concerns that emerged in this case are also discussed.

  6. Treatment of Severe Edema in Children with Nephrotic Syndrome with Diuretics Alone — A Prospective Study

    Science.gov (United States)

    Kapur, Gaurav; Valentini, Rudolph P.; Imam, Abubakr A.; Mattoo, Tej K.

    2009-01-01

    Background and objective: Severe edema in children with nephrotic syndrome (NS) may be associated with volume contraction (VC) or volume expansion (VE). Usually, severe edema in children is treated with intravenous (IV) albumin and diuretics, which is appropriate for VC patients. However, in VE patients, this can precipitate fluid overload. The objective of this study was to evaluate treatment of severe edema in NS with diuretics alone. Design, setting, participants, & measurements: Thirty NS patients with severe edema were enrolled in this prospective study in two phases. VC was diagnosed based on fractional excretion of sodium (FeNa) diuretics alone and 9 VC patients received albumin and furosemide. There was no difference in hospital stay and weight loss in VC and VE groups after treatment. Conclusions: FeNa is useful in distinguishing VC versus VE in NS children with severe edema. The use of diuretics alone in VE patients is safe and effective. PMID:19406963

  7. Vitamin D status is insufficient in the majority of children at diagnosis of nephrotic syndrome

    DEFF Research Database (Denmark)

    Nielsen, Cecilie Ane; Jensen, Jens-Erik Bech; Cortes, Dina

    2015-01-01

    (p = 0.048). CONCLUSION: The vitamin D status was insufficient in 93% of the patients. We suggest that vitamin D status in children with NS be measured routinely at the time of diagnosis so that an individual treatment strategy for vitamin D defi-ciency can be given. Further studies are needed......INTRODUCTION: Children with nephrotic syndrome (NS) are treated for at least 12 weeks with high doses of prednisolone, which may be harmful to the bones. Vitamin D deficiency is also harmful to the bones. METHODS: This was a prospective study of consecutive children with first episode of NS...... at the time of their diagnosis before treatment with glucocorticoids. The following plasma levels were measured: 25-hydroxy-vitamin-D (25(OH)D), albumin, ionised calcium, phosphate, parathyroid hormone (PTH), alkaline phosphatase and creatinine. The glomerular filtration rate (GFR) was estimated from...

  8. Vitamin D status is insufficient in the majority of children at diagnosis of nephrotic syndrome

    DEFF Research Database (Denmark)

    Nielsen, Cecilie Ane; Jensen, Jens-Erik Bech; Cortes, Dina

    2015-01-01

    (p = 0.048). CONCLUSION: The vitamin D status was insufficient in 93% of the patients. We suggest that vitamin D status in children with NS be measured routinely at the time of diagnosis so that an individual treatment strategy for vitamin D deficiency can be given. Further studies are needed......INTRODUCTION: Children with nephrotic syndrome (NS) are treated for at least 12 weeks with high doses of prednisolone, which may be harmful to the bones. Vitamin D deficiency is also harmful to the bones. METHODS: This was a prospective study of consecutive children with first episode of NS...... at the time of their diagnosis before treatment with glucocorticoids. The following plasma levels were measured: 25-hydroxy-vitamin-D (25(OH)D), albumin, ionised calcium, phosphate, parathyroid hormone (PTH), alkaline phosphatase and creatinine. The glomerular filtration rate (GFR) was estimated from...

  9. Serum lipoprotein (a) concentration in patients with nephrotic syndrome and its clinical implication.

    Science.gov (United States)

    Yang, X; Wang, H; Zhu, Z; Deng, A

    1998-01-01

    Serum lipoprotein(a) [Lp(a)] concentration was determined in 42 patients with primary nephrotic syndrome (NS) and the relationships between Lp (a) and plasma lipids, apolipoproteins, serum creatinine (Scr), albumin, urinary proteins (Upro) were also analyzed. The results showed that: (1) serum Lp(a) concentrations in the patients with NS were higher than those in healthy controls; (2) the levels of serum Lp(a) were correlated positively with total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), very low density lipoprotein cholesterol (VLDL-C), apolipoprotein B (Apo-B), Upros (Upro). It is concluded that the NS patients had the potential risk of suffering from coronary artery disease, glomerular sclerosis and thrombosis. The remission of NS may partially decrease the serum Lp(a) levels. Further studies are needed to explore the prevention and treatment of dislipedemia in patients with NS.

  10. Mutation spectrum of genes associated with steroid-resistant nephrotic syndrome in Chinese children.

    Science.gov (United States)

    Wang, Ying; Dang, Xiqiang; He, Qingnan; Zhen, Yan; He, Xiaoxie; Yi, Zhuwen; Zhu, Kuichun

    2017-08-20

    Approximately 20% of children with idiopathic nephrotic syndrome do not respond to steroid therapy. More than 30 genes have been identified as disease-causing genes for the steroid-resistant nephrotic syndrome (SRNS). Few reports were from the Chinese population. The coding regions of genes commonly associated with SRNS were analyzed to characterize the gene mutation spectrum in children with SRNS in central China. The first phase study involved 38 children with five genes (NPHS1, NPHS2, PLCE1, WT1, and TRPC6) by Sanger sequencing. The second phase study involved 33 children with 17 genes by next generation DNA sequencing (NGS. 22 new patients, and 11 patients from first phase study but without positive findings). Overall deleterious or putatively deleterious gene variants were identified in 19 patients (31.7%), including four NPHS1 variants among five patients and three PLCE1 variants among four other patients. Variants in COL4A3, COL4A4, or COL4A5 were found in six patients. Eight novel variants were identified, including two in NPHS1, two in PLCE1, one in NPHS2, LAMB2, COL4A3, and COL4A4, respectively. 55.6% of the children with variants failed to respond to immunosuppressive agent therapy, while the resistance rate in children without variants was 44.4%. Our results show that screening for deleterious variants in some common genes in children clinically suspected with SRNS might be helpful for disease diagnosis as well as prediction of treatment efficacy and prognosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Immunosupressive therapy in children with steroid-resistant nephrotic syndrome: single center experience.

    Science.gov (United States)

    Echeverri, Catalina Velez; Valencia, Gustavo Adolfo Zuluaga; Higuita, Lina Maria Serna; Gayubo, Ana Katherina Serrano; Ochoa, Carolina Lucia; Rosas, Luisa Fernanda Rojas; Muñoz, Laura Carolina; Sierra, Javier; Zuleta, Jhon Jairo; Ruiz, Juan José Vanegas

    2013-01-01

    [corrected] Nephrotic syndrome is one of the most frequent glomerular diseases among children, and steroid therapy remains as the treatment choice. In spite of this, 10 to 15% of the patients are steroidresistant, and the best therapy for such cases has never been defined. Mycophenolate acid (MA) is one of the treatments used in such situations. To describe the clinical behavior of children diagnosed with steroid-resistant nephrotic syndrome (SRNS) and to assess the therapeutic response to MA. This was a retrospective and descriptive study. 26 clinical records of patients with SRNS; 70% male and 30% female. All patients underwent kidney biopsies, which showed a predominance of focal segmental glomerulosclerosis (FSGS). The immunosuppresive drugs used were: Mycophenolate mofetil (MMF) 100%, Cyclosporine 69.2%, Cyclophosphamide 23.1%, and Rituximab 23%. One month after treatment initiation with MMF 61.5% achieved remission. The median of relapses per year for the patients was 3 (p25: 2.75 - p75: 4). This median became 1 (p25: 1 - p75: 3.25) after using this medication (p = 0.08). Furthermore, prior to the start of the MMF treatment, the median of the steroid dose was 1 (p25: 0.5- p75: 1.62) mg/k/day. After using MMF, this median became 0.07 (p25: 0 - p75: 0.55) mg/k/day (p < 0.001), in 8 patients prednisolone was stopped. In our experience, treatment with MMF showed positive results such as decrease in the frequency of relapses, less proteinuria, and reduction in the dose of steroids administered without deterioration of glomerular filtration rates. However, more studies are needed to assess efficacy, safety, and optimal dosage.

  12. Immunosupressive therapy in children with steroid-resistant nephrotic syndrome: single center experience

    Directory of Open Access Journals (Sweden)

    Catalina Velez Echeverri

    2013-09-01

    Full Text Available INTODUCTION: Nephrotic syndrome is one of the most frequent glomerular diseases among children, and steroid therapy remains as the treatment choice. In spite of this, 10 to 15% of the patients are steroidresistant, and the best therapy for such cases has never been defined. Mycophenolate acid (MA is one of the treatments used in such situations. OBJECTIVE: To describe the clinical behavior of children diagnosed with steroid-resistant nephrotic syndrome (SRNS and to assess the therapeutic response to MA. METHODS: This was a retrospective and descriptive study. RESULTS: 26 clinical records of patients with SRNS; 70% male and 30% female. All patients underwent kidney biopsies, which showed a predominance of focal segmental glomerulosclerosis (FSGS. The immunosuppresive drugs used were: Mycophenolate mofetil (MMF 100%, Cyclosporine 69.2%, Cyclophosphamide 23.1%, and Rituximab 23%. One month after treatment initiation with MMF 61.5% achieved remission. The median of relapses per year for the patients was 3 (p25: 2.75 - p75: 4. This median became 1 (p25: 1 - p75: 3.25 after using this medication (p = 0.08. Furthermore, prior to the start of the MMF treatment, the median of the steroid dose was 1 (p25: 0.5- p75: 1.62 mg/k/day. After using MMF, this median became 0.07 (p25: 0 - p75: 0.55 mg/k/day (p < 0.001, in 8 patients prednisolone was stopped. CONCLUSION: In our experience, treatment with MMF showed positive results such as decrease in the frequency of relapses, less proteinuria, and reduction in the dose of steroids administered without deterioration of glomerular filtration rates. However, more studies are needed to assess efficacy, safety, and optimal dosage.

  13. Nephrotic Syndrome

    Science.gov (United States)

    ... Fitness Diseases & Conditions Infections Drugs & Alcohol School & Jobs Sports Expert Answers (Q&A) Staying ... español Síndrome nefrótico Kids with too much protein in their urine (pee), sudden weight gain, and ...

  14. Nephrotic syndrome

    Science.gov (United States)

    ... panel Blood urea nitrogen (BUN) Creatinine - blood test Creatinine clearance - urine test Urinalysis Fats are often also present in the urine. Blood cholesterol and triglyceride levels may be high. A kidney biopsy may be needed to find ...

  15. Síndromes nefróticos congénitos y hereditarios Congenital and heritable nephrotic syndromes

    Directory of Open Access Journals (Sweden)

    Sandalio Durán Álvarez

    2011-03-01

    Full Text Available En los últimos años se han identificado muchos síndromes nefróticos familiares y esporádicos que no responden a los tratamientos habituales (esteroides e inmunosupresores, evolucionan con relativa rapidez a la insuficiencia renal crónica y se producen por mutaciones genéticas. La mayoría de los síndromes nefróticos que se trasmiten genéticamente y que pueden ser congénitos, presentarse en el primer año de la vida, o en el niño mayor, son atribuidos a mutaciones en los genes NPHS1, NPHS2, WT1 y LAMB2. Otros síndromes nefróticos producidos por mutaciones genéticas pueden no manifestarse hasta la adultez. El objetivo fundamental de esta revisión fue llamar la atención sobre los síndromes nefróticos producidos por mutaciones genéticas en los que no sólo no se obtienen resultados con los tratamientos inmunosupresores, si no en los que dichos tratamientos pueden ser perjudiciales para el paciente.In past years many familial and sporadic nephrotic syndromes refractory to usual treatments (steroids and immunosuppressives, evolve quickly to a chronic renal failure produced by genetic mutations. Most of nephrotic syndromes genetically transmitted and that may be congenital, present in the first year of life or in the older child, are attributable to NPHS1, NPHS2, WT1 and KLAMB2 gen mutations. Other nephrotic syndromes produced by genetic mutations may not appear until adulthood. The main objective of present review was to alert on the nephrotic syndromes produced by genetic mutations without response to immunosuppressive treatments, but on those in which such treatment may be dangerous for patient.

  16. Prediction of Negative Conversion Days of Childhood Nephrotic Syndrome Based on the Improved Backpropagation Neural Network with Momentum

    Directory of Open Access Journals (Sweden)

    Yi-jun Liu

    2015-12-01

    Full Text Available Childhood nephrotic syndrome is a chronic disease harmful to growth of children. Scientific and accurate prediction of negative conversion days for children with nephrotic syndrome offers potential benefits for treatment of patients and helps achieve better cure effect. In this study, the improved backpropagation neural network with momentum is used for prediction. Momentum speeds up convergence and maintains the generalization performance of the neural network, and therefore overcomes weaknesses of the standard backpropagation algorithm. The three-tier network structure is constructed. Eight indicators including age, lgG, lgA and lgM, etc. are selected for network inputs. The scientific computing software of MATLAB and its neural network tools are used to create model and predict. The training sample of twenty-eight cases is used to train the neural network. The test sample of six typical cases belonging to six different age groups respectively is used to test the predictive model. The low mean absolute error of predictive results is achieved at 0.83. The experimental results of the small-size sample show that the proposed approach is to some degree applicable for the prediction of negative conversion days of childhood nephrotic syndrome.

  17. Nephrin redistribution on podocytes is a potential mechanism for proteinuria in patients with primary acquired nephrotic syndrome.

    Science.gov (United States)

    Doublier, S; Ruotsalainen, V; Salvidio, G; Lupia, E; Biancone, L; Conaldi, P G; Reponen, P; Tryggvason, K; Camussi, G

    2001-05-01

    We investigated the distribution of nephrin by immunofluorescence microscopy in renal biopsies of patients with nephrotic syndrome: 13 with membranous glomerulonephritis (GN), 10 with minimal change GN, and seven with focal segmental glomerulosclerosis. As control, six patients with IgA GN without nephrotic syndrome and 10 normal controls were studied. We found an extensive loss of staining for nephrin and a shift from a podocyte-staining pattern to a granular pattern in patients with nephrotic syndrome, irrespective of the primary disease. In membranous GN, nephrin was co-localized with IgG immune deposits. In the attempt to explain these results, we investigated in vitro whether stimuli acting on the cell cytoskeleton, known to be involved in the pathogenesis of GN, may induce redistribution of nephrin on the surface of human cultured podocytes. Aggregated but not disaggregated human IgG(4), plasmalemmal insertion of membrane attack complex of complement, tumor necrosis factor-alpha, and puromycin, induced the shedding of nephrin with a loss of surface expression. This phenomenon was abrogated by cytochalasin and sodium azide. These results suggest that the activation of cell cytoskeleton may modify surface expression of nephrin allowing a dislocation from plasma membrane to an extracellular site.

  18. Astragalus in the Prevention of Upper Respiratory Tract Infection in Children with Nephrotic Syndrome: Evidence-Based Clinical Practice

    Directory of Open Access Journals (Sweden)

    Chuan Zou

    2013-01-01

    Full Text Available Aims. To explore whether Astragalus or its formulations could prevent upper respiratory infection in children with nephrotic syndrome and how best to use it. Methods. We transformed a common clinical question in practice to an answerable question according to the PICO principle. Databases, including the Cochrane Library (Issue 5, 2012, PUBMED (1966–2012.8, CBM (1978–2012.8, VIP (1989–2012.8, and CNKI (1979–2012.8, were searched to identify Cochrane systematic reviews and clinical trials. Then, the quality of and recommendations from the clinical evidence were evaluated using the GRADEpro software. Results. The search yielded 537 papers. Only two studies with high validity were included for synthesis calculations. The results showed that Astragalus granules could effectively reduce URTI in children with nephrotic syndrome compared with prednisone treatment alone (23.9% versus 42.9%; RR = 0.56 and 95% CI = 0.33–0.93. The dose of Astragalus granules was 2.25 gram (equivalent to 15 gram crude Astragalus twice per day, at least for 3–6 months. The level of evidence quality was low, but we still recommended the evidence to the patient according to GRADEpro with the opinion of the expert. Followup showed the incidence of URTI in this child decreased significantly. Conclusions. Astragalus granules may reduce the incidence of URTI in children with nephrotic syndrome.

  19. Mutations in the evolutionarily highly conserved KEOPS complex genes cause nephrotic syndrome with microcephaly

    Science.gov (United States)

    Braun, Daniela A.; Rao, Jia; Mollet, Geraldine; Schapiro, David; Daugeron, Marie-Claire; Tan, Weizhen; Gribouval, Olivier; Boyer, Olivia; Revy, Patrick; Jobst-Schwan, Tilman; Schmidt, Johanna Magdalena; Lawson, Jennifer A.; Schanze, Denny; Ashraf, Shazia; Boddaert, Nathalie; Collinet, Bruno; Martin, Gaëlle; Liger, Dominique; Lovric, Svjetlana; Furlano, Monica; Guerrera, I. Chiara; Sanchez-Ferras, Oraly; Menten, Björn; Vergult, Sarah; De Rocker, Nina; Airik, Merlin; Hermle, Tobias; Shril, Shirlee; Widmeier, Eugen; Gee, Heon Yung; Choi, Won-Il; Sadowski, Carolin E.; Pabst, Werner L.; Warejko, Jillian; Daga, Ankana; LeBerre, Tamara Basta; Matejas, Verena; Behnam, Babak; Beeson, Brendan; Begtrup, Amber; Bruce, Malcolm; Ch'ng, Gaik-Siew; Lin, Shuan-Pei; Chang, Jui-Hsing; Chen, Chao-Huei; Cho, Megan T.; Gipson, Patrick E.; Hsu, Chyong-Hsin; Kari, Jameela A.; Ke, Yu-Yuan; Kiraly-Borri, Cathy; Lai, Wai-ming; Lemyre, Emmanuelle; Littlejohn, Rebecca Okasha; Masri, Amira; Moghtaderi, Mastaneh; Nakamura, Kazuyuki; Praet, Marleen; Prasad, Chitra; Prytula, Agnieszka; Roeder, Elizabeth; Rump, Patrick; Schnur, Rhonda E.; Shiihara, Takashi; Sinha, Manish; Soliman, Neveen A; Soulami, Kenza; Sweetser, David A.; Tsai, Wen-Hui; Tsai, Jeng-Daw; Vester, Udo; Viskochil, David H.; Vatanavicharn, Nithiwat; Waxler, Jessica L.; Wolf, Matthias T.F.; Wong, Sik-Nin; Poduri, Annapurna; Truglio, Gessica; Mane, Shrikant; Lifton, Richard P.; Bouchard, Maxime; Kannu, Peter; Chitayat, David; Magen, Daniella; Calleweart, Bert; van Tilbeurgh, Herman; Zenker, Martin; Antignac, Corinne; Hildebrandt, Friedhelm

    2018-01-01

    Galloway-Mowat syndrome (GAMOS) is a severe autosomal-recessive disease characterized by the combination of early-onset steroid-resistant nephrotic syndrome (SRNS) and microcephaly with brain anomalies. To date, mutations of WDR73 are the only known monogenic cause of GAMOS and in most affected individuals the molecular diagnosis remains elusive. We here identify recessive mutations of OSGEP, TP53RK, TPRKB, or LAGE3, encoding the 4 subunits of the KEOPS complex in 33 individuals of 30 families with GAMOS. CRISPR/Cas9 knockout in zebrafish and mice recapitulates the human phenotype of microcephaly and results in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibits cell proliferation, which human mutations fail to rescue, and knockdown of either gene activates DNA damage response signaling and induces apoptosis. OSGEP and TP53RK molecularly interact and co-localize with the actin-regulating ARP2/3 complex. Furthermore, knockdown of OSGEP and TP53RK induces defects of the actin cytoskeleton and reduces migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identify 4 novel monogenic causes of GAMOS, describe the first link between KEOPS function and human disease, and delineate potential pathogenic mechanisms. PMID:28805828

  20. Mutations in KEOPS-complex genes cause nephrotic syndrome with primary microcephaly.

    Science.gov (United States)

    Braun, Daniela A; Rao, Jia; Mollet, Geraldine; Schapiro, David; Daugeron, Marie-Claire; Tan, Weizhen; Gribouval, Olivier; Boyer, Olivia; Revy, Patrick; Jobst-Schwan, Tilman; Schmidt, Johanna Magdalena; Lawson, Jennifer A; Schanze, Denny; Ashraf, Shazia; Ullmann, Jeremy F P; Hoogstraten, Charlotte A; Boddaert, Nathalie; Collinet, Bruno; Martin, Gaëlle; Liger, Dominique; Lovric, Svjetlana; Furlano, Monica; Guerrera, I Chiara; Sanchez-Ferras, Oraly; Hu, Jennifer F; Boschat, Anne-Claire; Sanquer, Sylvia; Menten, Björn; Vergult, Sarah; De Rocker, Nina; Airik, Merlin; Hermle, Tobias; Shril, Shirlee; Widmeier, Eugen; Gee, Heon Yung; Choi, Won-Il; Sadowski, Carolin E; Pabst, Werner L; Warejko, Jillian K; Daga, Ankana; Basta, Tamara; Matejas, Verena; Scharmann, Karin; Kienast, Sandra D; Behnam, Babak; Beeson, Brendan; Begtrup, Amber; Bruce, Malcolm; Ch'ng, Gaik-Siew; Lin, Shuan-Pei; Chang, Jui-Hsing; Chen, Chao-Huei; Cho, Megan T; Gaffney, Patrick M; Gipson, Patrick E; Hsu, Chyong-Hsin; Kari, Jameela A; Ke, Yu-Yuan; Kiraly-Borri, Cathy; Lai, Wai-Ming; Lemyre, Emmanuelle; Littlejohn, Rebecca Okashah; Masri, Amira; Moghtaderi, Mastaneh; Nakamura, Kazuyuki; Ozaltin, Fatih; Praet, Marleen; Prasad, Chitra; Prytula, Agnieszka; Roeder, Elizabeth R; Rump, Patrick; Schnur, Rhonda E; Shiihara, Takashi; Sinha, Manish D; Soliman, Neveen A; Soulami, Kenza; Sweetser, David A; Tsai, Wen-Hui; Tsai, Jeng-Daw; Topaloglu, Rezan; Vester, Udo; Viskochil, David H; Vatanavicharn, Nithiwat; Waxler, Jessica L; Wierenga, Klaas J; Wolf, Matthias T F; Wong, Sik-Nin; Leidel, Sebastian A; Truglio, Gessica; Dedon, Peter C; Poduri, Annapurna; Mane, Shrikant; Lifton, Richard P; Bouchard, Maxime; Kannu, Peter; Chitayat, David; Magen, Daniella; Callewaert, Bert; van Tilbeurgh, Herman; Zenker, Martin; Antignac, Corinne; Hildebrandt, Friedhelm

    2017-10-01

    Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms.

  1. An inducible mouse model of podocin-mutation-related nephrotic syndrome.

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    Mansoureh Tabatabaeifar

    Full Text Available Mutations in the NPHS2 gene, encoding podocin, cause hereditary nephrotic syndrome. The most common podocin mutation, R138Q, is associated with early disease onset and rapid progression to end-stage renal disease. Knock-in mice carrying a R140Q mutation, the mouse analogue of human R138Q, show developmental arrest of podocytes and lethal renal failure at neonatal age. Here we created a conditional podocin knock-in model named NPHS2 R140Q/-, using a tamoxifen-inducible Cre recombinase, which permits to study the effects of the mutation in postnatal life. Within the first week of R140Q hemizygosity induction the animals developed proteinuria, which peaked after 4-5 weeks. Subsequently the animals developed progressive renal failure, with a median survival time of 12 (95% CI: 11-13 weeks. Foot process fusion was observed within one week, progressing to severe and global effacement in the course of the disease. The number of podocytes per glomerulus gradually diminished to 18% compared to healthy controls 12-16 weeks after induction. The fraction of segmentally sclerosed glomeruli was 25%, 85% and 97% at 2, 4 and 8 weeks, respectively. Severe tubulointerstitial fibrosis was present at later disease stage and was correlated quantitatively with the level of proteinuria at early disease stages. While R140Q podocin mRNA expression was elevated, protein abundance was reduced by more than 50% within one week following induction. Whereas miRNA21 expression persistently increased during the first 4 weeks, miRNA-193a expression peaked 2 weeks after induction. In conclusion, the inducible R140Q-podocin mouse model is an auspicious model of the most common genetic cause of human nephrotic syndrome, with a spontaneous disease course strongly reminiscent of the human disorder. This model constitutes a valuable tool to test the efficacy of novel pharmacological interventions aimed to improve podocyte function and viability and attenuate proteinuria

  2. A Prospective Observational Survey on the Long-Term Effect of LDL Apheresis on Drug-Resistant Nephrotic Syndrome

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    Eri Muso

    2015-08-01

    Full Text Available Background/Aims: LDL apheresis (LDL-A is used for drug-resistant nephrotic syndrome (NS as an alternative therapy to induce remission by improvement of hyperlipidemia. Several clinical studies have suggested the efficacy of LDL-A for refractory NS, but the level of evidence remains insufficient. A multicenter prospective study, POLARIS (Prospective Observational Survey on the Long-Term Effects of LDL Apheresis on Drug-Resistant Nephrotic Syndrome, was conducted to evaluate its clinical efficacy with high-level evidence. Methods: Patients with NS who showed resistance to primary medication for at least 4 weeks were prospectively recruited to the study and treated with LDL-A. The long-term outcome was evaluated based on the rate of remission of NS 2 years after treatment. Factors affecting the outcome were also examined. Results: A total of 58 refractory NS patients from 40 facilities were recruited and enrolled as subjects of the POLARIS study. Of the 44 subjects followed for 2 years, 21 (47.7% showed remission of NS based on a urinary protein (UP level Conclusions: Almost half of the cases of drug-resistant NS showed remission 2 years after LDL-A. Improvement of nephrotic parameters at termination of the LDL-A treatment was a predictor of a favorable outcome.

  3. Traditional Chinese Medicine for Refractory Nephrotic Syndrome: Strategies and Promising Treatments

    Science.gov (United States)

    Tu, Yuan-Chao

    2018-01-01

    Refractory nephrotic syndrome (RNS) is an immune-related kidney disease with poor clinical outcomes. Standard treatments include corticosteroids as the initial therapy and other immunosuppressants as second-line options. A substantial proportion of patients with RNS are resistant to or dependent on immunosuppressive drugs and often experience unremitting edema and proteinuria, cycles of remission and relapse, and/or serious adverse events due to long-term immunosuppression. Traditional Chinese medicine has a long history of treating complicated kidney diseases and holds great potential for providing effective treatments for RNS. This review describes the Chinese medical theories relating to the pathogenesis of RNS and discusses the strategies and treatment options using Chinese herbal medicine. Available preclinical and clinical evidence strongly supports the integration of traditional Chinese medicine and Western medicine for improving the outcome of RNS. Herbal medicine such as Astragalus membranaceus, Stephania tetrandra S. Moore, and Tripterygium wilfordii Hook F can serve as the alternative therapy when patients fail to respond to immunosuppression or as the complementary therapy to improve therapeutic efficacy and reduce side effects of immunosuppressive agents. Wuzhi capsules (Schisandra sphenanthera extract) with tacrolimus and tetrandrine with corticosteroids are two herb-drug combinations that have shown great promise and warrant further studies. PMID:29507594

  4. Genotyping Rs2274625 Marker in NPHS2 Gene Associated with Nephrotic Syndrome in Isfahan Population

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    L Esmaili Chamgordani

    2015-12-01

    Full Text Available Introduction: Nephrotic syndrome (NS is a genetic disease belonging to a heterogeneous group of glomerular disorders, which mainly occurs within the children. Linkage analysis using single nucleotide polymorphisms (SNP is used as an indirect method in molecular diagnosis of the disease. A large number of SNP markers have been introduced in NPHS2gene in the available electronic databases. Method: In the present study, the genotype and informative status of rs2274625 marker in NPHS2 genewas investigated in 120 unrelated healthy individuals using Tetra-primer ARMS PCR technique and newly designed primers. Allelic frequency and presence of Hardy Weinberg Equilibrium (HWE was estimated using GenePop website. Furthermore, PowerMarker software was utilized in order to compute the index of polymorphism information content (PIC. Results: The study results indicated allele frequency of 97% and 3% for C and T alleles, respectively, in regard with rs2274625 marker within Isfahan population. Moreover, the PIC for the rs2274625 marker was 0.5%, and HWE revealed the equilibruim of the study population in regard with the related marker. Conclusion: As the study findings indicated, rs2274625 could be introduced as an SNP marker in the linkage analysis in order to molecularly trace NPHS2 gene mutations in molecular NS diagnosis in Isfahan population as a representative sample of the Iranian population.

  5. Polimiosite associada à síndrome nefrótica Polymyositis associated with nephrotic syndrome

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    Renato Oliveira Freire

    2010-08-01

    Full Text Available A polimiosite (PM é uma doença sistêmica do grupo das miopatias inflamatórias idiopáticas, clinicamente caracterizada por fraqueza muscular proximal e simétrica. Há relatos na literatura de PM associada a neoplasias, doenças autoimunes e infecções virais. Entretanto, a associação entre PM e nefropatia não é frequente. Descrevemos o caso de um paciente com polimiosite que evoluiu com síndrome nefrótica devido à presença de glomerulonefrite mesangialPolymyositis (PM is a systemic disease of the idiopathic inflammatory myopathy group, clinically characterized by symmetric and proximal muscle weakness. There are reports in literature of PM associated with malignancies, autoimmune diseases, and viral infections. However, the association between PM and nephropathy is not common. We describe a case report of a patient with polymyositis who developed nephrotic syndrome due to mesangial glomerulonephritis

  6. Non-Autoimmune Subclinical and Overt Hypothyroidism in Idiopathic Steroid-resistant Nephrotic Syndrome in Children.

    Science.gov (United States)

    Marimuthu, Vidhya; Krishnamurthy, Sriram; Rajappa, Medha

    2017-11-15

    To evaluate the frequency of non-autoimmune subclinical and overt hypothyroidism in children with idiopathic steroid-resistant nephrotic syndrome (SRNS). This cross-sectional study recruited 30 children (age 1-18 y) with idiopathic SRNS; and 30 healthy controls. Serum T3, T4 and TSH were performed in cases as well as controls. Anti-thyroid peroxidase and anti-thyroglobulin antibody tests were performed in all cases. Non-autoimmune subclinical or overt hypothyroidism was detected in 10 out of 30 children with idiopathic SRNS; 2 had overt hypothyroidism, while 8 patients had subclinical hypothyroidism. Children with SRNS had a mean (SD) TSH value 4.55 (4.64) mIU/L that was higher as compared to controls (1.88 (1.04) mIU/L) (Phypothyroidism (2 cases) and grade III subclinical hypothyroidism (1 case) were subsequently started on levothyroxine therapy. The prevalence of subclinical and overt hypothyroidism seems to be high in idiopathic SRNS, with almost one-third of children having overt or subclinical non-autoimmune hypothyroidism.

  7. Nephrotic syndrome induced by dibasic sodium phosphate injections for twenty-eight days in rats.

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    Tsuchiya, Noriko; Torii, Mikinori; Narama, Isao; Matsui, Takane

    2009-04-01

    Sprague-Dawley rats received once daily tail-vein injections of 360 mM dibasic sodium phosphate solution at 8 mL/kg for fourteen or twenty-eight days. Clinical examination revealed persistent proteinuria from three days after the first dosing and thereafter severe proteinuria from eight days or later in the phosphate-treated groups. Proteinuria developed without remission even after fourteen-day withdrawal in the fourteen-day dosed group. Phosphate-treated animals developed lipemia, hypercholesterolemia, anemia, higher serum fibrinogen levels, and lower serum albumin/globulin ratios on day 29. Renal weight increased significantly compared with control animals, and the kidneys appeared pale and enlarged with a rough surface. Histopathologically, glomerular changes consisted of mineralization in whole glomeruli, glomerular capillary dilatation, partial adhesion of glomerular tufts to Bowman's capsule, and mesangiolysis. Ultrastructural lesions such as an increased number of microvilli, effacement of foot processes, and thickening of the glomerular basement membrane, and immunocytochemical changes in podocytes, mainly decreased podoplanin-positive cells and increased desmin expression, were also conspicuous in the phosphate-treated rats for twenty-eight days. Marked tubulointerstitial lesions were tubular regeneration and dilatation, protein casts, mineralization in the basement membrane, focal interstitial inflammation, and fibrosis in the cortex. These clinical and morphological changes were similar to features of human nephrotic syndrome.

  8. Forced expression of laminin β1 in podocytes prevents nephrotic syndrome in mice lacking laminin β2, a model for Pierson syndrome

    Science.gov (United States)

    Suh, Jung Hee; Jarad, George; VanDeVoorde, Rene G.; Miner, Jeffrey H.

    2011-01-01

    Pierson syndrome is a congenital nephrotic syndrome with ocular and neurological defects caused by mutations in LAMB2, the gene encoding the basement membrane protein laminin β2 (Lamβ2). It is the kidney glomerular basement membrane (GBM) that is defective in Pierson syndrome, as Lamβ2 is a component of laminin-521 (LM-521; α5β2γ1), the major laminin in the mature GBM. In both Pierson syndrome and the Lamb2−/− mouse model for this disease, laminin β1 (Lamβ1), a structurally similar homolog of Lamβ2, is marginally increased in the GBM, but it fails to fully compensate for the loss of Lamβ2, leading to the filtration barrier defects and nephrotic syndrome. Here we generated several lines of Lamβ1 transgenic mice and used them to show that podocyte-specific Lamβ1 expression in Lamb2−/− mice abrogates the development of nephrotic syndrome, correlating with a greatly extended lifespan. In addition, the more Lamβ1 was expressed, the less urinary albumin was excreted. Transgenic Lamβ1 expression increased the level of Lamα5 in the GBM of rescued mice, consistent with the desired increased deposition of laminin-511 (α5β1γ1) trimers. Ultrastructural analysis revealed occasional knob-like subepithelial GBM thickening but intact podocyte foot processes in aged rescued mice. These results suggest the possibility that up-regulation of LAMB1 in podocytes, should it become achievable, would likely lessen the severity of nephrotic syndrome in patients carrying LAMB2 mutations. PMID:21876163

  9. Forced expression of laminin beta1 in podocytes prevents nephrotic syndrome in mice lacking laminin beta2, a model for Pierson syndrome.

    Science.gov (United States)

    Suh, Jung Hee; Jarad, George; VanDeVoorde, Rene G; Miner, Jeffrey H

    2011-09-13

    Pierson syndrome is a congenital nephrotic syndrome with ocular and neurological defects caused by mutations in LAMB2, the gene encoding the basement membrane protein laminin β2 (Lamβ2). It is the kidney glomerular basement membrane (GBM) that is defective in Pierson syndrome, as Lamβ2 is a component of laminin-521 (LM-521; α5β2γ1), the major laminin in the mature GBM. In both Pierson syndrome and the Lamb2(-/-) mouse model for this disease, laminin β1 (Lamβ1), a structurally similar homolog of Lamβ2, is marginally increased in the GBM, but it fails to fully compensate for the loss of Lamβ2, leading to the filtration barrier defects and nephrotic syndrome. Here we generated several lines of Lamβ1 transgenic mice and used them to show that podocyte-specific Lamβ1 expression in Lamb2(-/-) mice abrogates the development of nephrotic syndrome, correlating with a greatly extended lifespan. In addition, the more Lamβ1 was expressed, the less urinary albumin was excreted. Transgenic Lamβ1 expression increased the level of Lamα5 in the GBM of rescued mice, consistent with the desired increased deposition of laminin-511 (α5β1γ1) trimers. Ultrastructural analysis revealed occasional knob-like subepithelial GBM thickening but intact podocyte foot processes in aged rescued mice. These results suggest the possibility that up-regulation of LAMB1 in podocytes, should it become achievable, would likely lessen the severity of nephrotic syndrome in patients carrying LAMB2 mutations.

  10. Clinical significance of measurement of plasma leptin and serum IL-6, IL-18 levels after treatment in patients with children nephrotic syndrome

    International Nuclear Information System (INIS)

    Wang Xiaoyan

    2011-01-01

    Objective: To explore the clinical significance of changes of plasma leptin and serum IL-6, IL-18 levels after treatment in patients with children nephrotic syndrome. Methods: Plasma leptin (with RIA) serum IL-6, IL-18 (with ELISA) levels were measured in 31 patients with children nephrotic syndrome both before and after treatment as well as in 30 controls. Results: Before treatment,the plasma leptin and serum IL-6, IL-18 levels were significantly higher than those in controls(P <0.01). After treatment for 3 months, the levels in patients though dropped markedly remained significantly higher than those in controls (P<0.05). Plasma leptin levels were positively correlated with IL-6, IL-18 levels (r=0.6138, 0.5784, P<0.01). Conclusion: Changes of plasma leptin and serum IL-6, IL-18 levels after treatment might be of prognostic importance in patients with children nephrotic syndrome. (authors)

  11. Biochemical alteration in children with idiopathic nephrotic syndrome associated with an increased risk of sensorineural hearing loss; additional insights in cochlear renal relationship.

    Science.gov (United States)

    El Mashad, Ghada Mohamed; Abo El Fotoh, Wafaa Moustafa M; Zein El Abedein, Ahmed Mahmoud; Abd El Sadek, Fatma Abd El Raoof

    2017-06-01

    Children with Idiopathic Nephrotic Syndrome (INS) are at risk of hearing loss due to the adverse impact of medications and related immunological and genetic factors on both cochlea and kidney. So this work was planned to evaluate hearing status in children with INS and to clarify the possible associated risk factors by interpreting the clinical and laboratory profiles of those children. Ninety children with INS aged 5-14 years [30 patients with steroid-sensitive nephrotic syndrome (SSNS), 30 patients with steroid dependent/frequently relapsing nephrotic syndrome (SDNS/FRNS), and 30 patients with steroid-resistant nephrotic syndrome (SRNS)], and 90 age and sex matched normal controls were enrolled into this study. Laboratory measurements of serum calcium, creatinine, cholesterol, blood urea and other relevant investigations were done. Pure tone audiometry was done with the sensory-neural hearing loss (SNHL) diagnosed when the level bone conduction was >20 dB and the difference in air to the bone gap was children with INS had SNHL, mostly of mild degree HL and primarily occurred at the lower frequencies. A highly significant statistical difference between controls and various types of nephrotic syndrome regarding pure tone audiometry measurements at frequencies 250, 500, 1000 Hz, whereas insignificant difference interpreting pure tone audiometry measurements in 2000, 4000 and 8000 Hz. Children with different phenotypes of nephrotic syndrome are at risk of sensorineural hearing impairment. The hazards associated with this impairment were higher blood pressure, hypercholesterolemia, hypoalbuminemia, and hypocalcemia. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. A descriptive retrospective study on children with newly diagnosed nephrotic syndrome presented to Tripoli Children Hospital during the period between Jan. to Dec. 2014

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    Naziha Ramadan Rhuma

    2016-10-01

    Full Text Available Introduction: Nephrotic syndrome is a clinical picture characterized by severe proteinuria, hypoalbuminemia, edema and hypercholesterolemia. A retrospective study was carried out in order to describe disease pattern in newly diagnosed nephrotic syndrome of children admitted to Tripoli children hospital during the year 2014. Methods: The medical data of 56 patients aged between 1 year and 11 years diagnosed with idiopathic nephrotic syndrome were analysed using SPSS software. The data included gender differences, sensitivity to steroid therapy, relapses during six months of follow up and the effect of variable factors such as family history, hypertension, hematuria, serum urea on the degree of relapse. Results: Out of 56 patients with newly diagnosed nephrotic syndrome (NS, 60.7% were boys and 39.3% were girls, with a mean age 4.2±2.2 years. Age  was related significantly to the response to steroid therapy, where 79.5% of patients aged between 2-8 years (group 1 had steroid sensitive nephrotic syndrome (SSNS compared with only 41.7% of patients aged less than 2 years or more than 8 years (group 2  (P<0.001.  Although girls relapsed more than boys (70.5% versus 57.1% during six months of therapy, this difference was not statistically significant. Similarly, no other factors measured such as family history of NS, hypertension, hematuria, serum complement and urea had any effect on the percentage of relapse in patients with newly diagnosed NS.  Conclusion: NS is one of the commonest reasons for admission to nephrology ward. It is more common in boys than girls. The age at presentation related significantly to the response to steroidal therapy. Regarding relapses, girls seems to relapse more frequent than boys and relapses was seen more in age group 1 than group 2, however, these differences were not significant. Other factors studied seems to have no effect on the relapse rate of children with newly diagnosed NS. Key-words:  Idiopathic

  13. Rac1 activation in podocytes induces the spectrum of nephrotic syndrome.

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    Robins, Richard; Baldwin, Cindy; Aoudjit, Lamine; Côté, Jean-François; Gupta, Indra R; Takano, Tomoko

    2017-08-01

    Hyper-activation of Rac1, a small GTPase, in glomerular podocytes has been implicated in the pathogenesis of familial proteinuric kidney diseases. However, the role of Rac1 in acquired nephrotic syndrome is unknown. To gain direct insights into this, we generated a transgenic mouse model expressing a doxycycline-inducible constitutively active form of Rac1 (CA-Rac1) in podocytes. Regardless of the copy number, proteinuria occurred rapidly within five days, and the histology resembled minimal change disease. The degree and severity of proteinuria were dependent on the transgene copy number. Upon doxycycline withdrawal, proteinuria resolved completely (one copy) or nearly completely (two copy). After one month of doxycycline treatment, two-copy mice developed glomerulosclerosis that resembled focal segmental glomerulosclerosis (FSGS) with urinary shedding of transgene-expressing podocytes. p38 MAPK was activated in podocytes upon CA-Rac1 induction while a p38 inhibitor attenuated proteinuria, podocyte loss, and glomerulosclerosis. Mechanistically, activation of Rac1 in cultured mouse podocytes reduced adhesiveness to laminin and induced redistribution of β1 integrin, and both were partially reversed by the p38 inhibitor. Activation of Rac1 in podocytes was also seen in kidney biopsies from patients with minimal change disease and idiopathic FSGS by immunofluorescence while sera from the same patients activated Rac1 in cultured human podocytes. Thus, activation of Rac1 in podocytes causes a spectrum of disease ranging from minimal change disease to FSGS, due to podocyte detachment from the glomerular basement membrane that is partially dependent on p38 MAPK. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  14. Relationship between ionized calcium and serum albumin level in children with idiopathic nephrotic syndrome

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    Viiola Irene Winata

    2016-10-01

    Full Text Available Background Nephrotic syndrome (NS patients frequently have abnormalities in calcium metabolism that manifest as hypocalcemia and reduced intestinal absorption of calcium. Hypocalcemia is initially attributed to hypoalbuminemia but it may also relate to a low level of ionized calcium. The ionized calcium level depends on the severity and duration of proteinuria. Objective To assess the rel ationship between ionized calcium and serum albumin level in idiopathic NS children. Methods An analytical study with cross-sectional design was applied to NS and healthy children between 1-14 years old in the Child Health Department of Hasan Sadikin Hospital, Bandung from December 2009 to April 2010. Ionized calcium was examined by Ca2 + analyzer AVL 980 with ion-selective electrodes (ISE methods. Results A total of34 subjects were recruited, consist of 17 NS and 17 healthy children. The mean ionized calcium and serum albumin level in NS children was 4.56 (SD 0.23 mg/dLand 1.45 (SD 0.24 g/dL, respectively. Statistical difference between ionized calcium level in NS and in healthy children was significant (P<0.05. Pearson correlation test between ionized calcium and serum albumin was significant (P<0.05 with correlation coefficient (r 0.53. We found the following equation to estimate ionized calcium (y based on the serum albumin level (x: y=3.84+0.49x. Conclusion There is a moderately positive linear relationship between ionized calcium and serum albumin level in NS children.

  15. Spectrum of nephrotic syndrome in adults: clinicopathological study from a single center in India.

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    Golay, Vishal; Trivedi, Mayuri; Kurien, Anila Abraham; Sarkar, Dipankar; Roychowdhary, Arpita; Pandey, Rajendra

    2013-01-01

    The etiology of nephrotic syndrome (NS) in adults varies depending on the geographical location and is poorly studied in the Indian subcontinent. Patients (≥16 years old) with NS presenting to our center and undergoing a kidney biopsy from April 2010 to September 2012 were included for this study. All biopsies were subjected to light and immunofluorescence microscopy, and electron microscopy in selected cases. The histopathological spectrum was analyzed according to the various clinical parameters. A total of 410 kidney biopsies were included for analysis. Two hundred and thirty seven (57.8%) patients were male and 173 (42.19%) patients were female. The average age at presentation was 33.68 ± 13.88 years. Among the patients, 88.05% (n = 361) were diagnosed with primary glomerular diseases (PGD) and 11.95% (n = 49) with secondary glomerular diseases (SGD). The most common histological lesions were focal segmental glomerulosclerosis (FSGS) (24.63%) followed by minimal change disease (MCD) (23.9%) and membranous nephropathy (MN) (22.44%). The most common form of SGD was lupus nephritis (LN) (6.58% of all cases). FSGS (28.27%) and MCD (21.96%) were the most common lesions in males and females, respectively. In the age groups of 16-29 years, 30-59 years, and ≥60 years, MCD (28.96%), MN (24%), and MN (40.74%) were the most common lesions, respectively, followed by FSGS in all groups (25.68%, 24.5%, and 18.52%, respectively). Among the patients, 27.07% had serum creatinine ≥1.5 mg/dL and 28.54% had either macroscopic or microscopic hematuria. FSGS is increasingly becoming the most common cause of adult NS. This trend in Asia is seen predominantly in countries of the Indian subcontinent.

  16. Effects of hypercholesterolemia of renal hemodynamics: study in patients with nephrotic syndrome.

    Science.gov (United States)

    Fuiano, G; Esposito, C; Sepe, V; Colucci, G; Bovino, M; Rosa, M; Balletta, M; Bellinghieri, G; Conte, G; Cianciaruso, B; Dal Canton, A

    1996-01-01

    Experimental and clinical studies have demonstrated a positive relationship between hyperlipidemia and rate of progression of renal disease, suggesting that lipids can induce or aggravate glomerular injury mainly by interacting with mesangial cells. Nevertheless, recently has been demonstrated that increased cholesterol levels can also induce endothelial cell dysfunction. Thus, since endothelium is known to play a major role in modulating the vascular tone, we have tested the possibility that hypercholesterolemia impairs the renal hemodynamics in patients with active nephrotic syndrome and elevated serum cholesterol levels. In this single-blind, nonrandom study, 12 patients were treated with pravastatin (group T, treated, n = 12) and 8 with placebo (group C, controls, n = 8). The controls were studied after the pravastatin group had been completed. Before starting the treatment the patients underwent basal determinations including routine laboratory investigations and PAH and inulin clearances. The same determinations were repeated after 48 h, and 6 and 12 weeks from the beginning of the treatment. The study at 48 h was performed to see if pravastatin had a direct, cholesterol-independent effect on renal function. The following basal results were reported (mean +/- SEM; group T vs. group C): serum cholesterol (mmol/l) 9.7 +/- 0.4 vs. 9.1 +/- 0.3 (NS); proteinuria (g/24 h): 6.2 +/- 0.2 vs. 7.0 +/- 0.7 (NS); PAH clearance (ml/min): 353 +/- 21 vs. 385 +/- 31 (NS); inulin clearance (ml/min): 62.5 +/- 7.7 vs. 67 +/- 9.3 (NS). After 48 h, no changes were observed in both groups. Subsequently, in group T, the following percentage changes of basal levels were observed: serum cholesterol -21.4 +/- 3.2% at 6 weeks (p < 0.05) and -34.9 +/- 3.2% at 12 weeks (p < 0.01); inulin clearance +3 +/- 3.7% at 6 weeks (NS) and +9.3 +/- 2.9% at 12 weeks (p < 0.05); PAH clearance +7 +/- 3.1% at 6 weeks (p < 0.05) and +21.2 +/- 5.5% at 12 weeks (p < 0.01). By contrast, no significant

  17. Systematic biomarker discovery and coordinative validation for different primary nephrotic syndromes using gas chromatography-mass spectrometry.

    Science.gov (United States)

    Lee, Jung-Eun; Lee, Yu Ho; Kim, Se-Yun; Kim, Yang Gyun; Moon, Ju-Young; Jeong, Kyung-Hwan; Lee, Tae Won; Ihm, Chun-Gyoo; Kim, Sooah; Kim, Kyoung Heon; Kim, Dong Ki; Kim, Yon Su; Kim, Chan-Duck; Park, Cheol Whee; Lee, Do Yup; Lee, Sang-Ho

    2016-07-01

    The goal of this study is to identify systematic biomarker panel for primary nephrotic syndromes from urine samples by applying a non-target metabolite profiling, and to validate their utility in independent sampling and analysis by multiplex statistical approaches. Nephrotic syndrome (NS) is a nonspecific kidney disorder, which is mostly represented by minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and membranous glomerulonephritis (MGN). Since urine metabolites may mirror disease-specific functional perturbations in kidney injury, we examined urine samples for distinctive metabolic changes to identify biomarkers for clinical applications. We developed unbiased multi-component covarianced models from a discovery set with 48 samples (12 healthy controls, 12 MCD, 12 FSGS, and 12 MGN). To extensively validate their diagnostic potential, new batch from 54 patients with primary NS were independently examined a year after. In the independent validation set, the model including citric acid, pyruvic acid, fructose, ethanolamine, and cysteine effectively discriminated each NS using receiver operating characteristic (ROC) analysis except MCD-MGN comparison; nonetheless an additional metabolite multi-composite greatly improved the discrimination power between MCD and MGN. Finally, we proposed the re-constructed metabolic network distinctively dysregulated by the different NSs that may deepen comprehensive understanding of the disease mechanistic, and help the enhanced identification of NS and therapeutic plans for future. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. R229Q Polymorphism of NPHS2 Gene in Group of Iraqi Children with Steroid-Resistant Nephrotic Syndrome

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    Shatha Hussain Ali

    2017-01-01

    Full Text Available Background. The polymorphism R229Q is one of the most commonly reported podocin sequence variations among steroid-resistant nephrotic syndromes (SRNS. Aim of the Study. We investigated the frequency and risk of this polymorphism among a group of Iraqi children with SRNS and steroid-sensitive nephrotic syndrome (SSNS. Patients and Methods. A prospective case control study which was conducted in Al-Imamein Al-Kadhimein Medical City, spanning the period from the 1st of April 2015 to 30th of November 2015. Study sample consisted of 54 children having NS, divided into 2 groups: patients group consisted of 27 children with SRNS, and control group involved 27 children with SSNS. Both were screened by real time polymerase chain reaction for R229Q in exon 5 of NPHS2 gene. Results. Molecular study showed R229Q polymorphism in 96.3% of SRNS and 100% of SSNS. There were no phenotypic or histologic characteristics of patients bearing homozygous R229Q polymorphism and the patients with heterozygous R229Q polymorphism. Conclusion. Polymorphism R229Q of NPHS2 gene is prevalent in Iraqi children with SRNS and SSNS. Further study needs to be done, for other exons and polymorphism of NPHS2 gene in those patients.

  19. [A Case of Advanced Transverse Colon Cancer with Nephrotic Syndrome Treated with Curative Resection and Complete Adjuvant Chemotherapy].

    Science.gov (United States)

    Sato, Nobutaka; Fuyuno, Seiya; Hatada, Teppei; Furuhashi, Takashi; Abe, Toshihiko

    2017-05-01

    A 74-year-old woman was diagnosed as having transverse colon cancer after diagnosis of nephrotic syndrome caused by membranous nephropathy. Although she had hypoproteinemia and hypoalbuminemia, we judged that she had no major nutritional problem. In previous, similar case reports, the use of human serum albumin and fresh-frozen plasma was suggested to be important to avoid complications in the perioperative period. Thus, we used the same in our patient in the perioperative period. In addition, we paid special attention to perioperative nutrition management and used total parenteral nutrition in perioperative period. We performed laparoscopic assisted right hemicolectomy. On the 15th day after the surgical resection, the patient was discharged without any problems. We considered that postoperative adjuvant chemotherapy with XELOX (CapeOX)should be performed because the TNM pathological stage was pStage III b. Regarding adjuvant chemotherapy for gastrointestinal cancer with nephrotic syndrome, no previous reports detailed the indications for postoperative adjuvant chemotherapy. Upon introduction of adjuvant chemotherapy, we determined adaptation in accordance with the general adaptation criteria. While observing the patient's progress with a nephrologist, we safely completed the scheduled 8 courses adjuvant chemotherapy.

  20. A randomized clinical trial indicates that levamisole increases the time to relapse in children with steroid-sensitive idiopathic nephrotic syndrome

    NARCIS (Netherlands)

    Gruppen, Mariken P.; Bouts, Antonia H.; Jansen-van der Weide, Marijke C.; Merkus, Maruschka P.; Zurowska, Aleksandra; Maternik, Michal; Massella, Laura; Emma, Francesco; Niaudet, Patrick; Cornelissen, Elisabeth A. M.; Schurmans, Thierry; Raes, Ann; van de Walle, Johan; van Dyck, Mieke; Gulati, Ashima; Bagga, Arvind; Davin, Jean-Claude

    2018-01-01

    Levamisole has been considered the least toxic and least expensive steroid-sparing drug for preventing relapses of steroid-sensitive idiopathic nephrotic syndrome (SSINS). However, evidence for this is limited as previous randomized clinical trials were found to have methodological limitations.

  1. A novel fibrillin-1 mutation in an egyptian marfan family: A proband showing nephrotic syndrome due to focal segmental glomerulosclerosis

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    Mohammad Al-Haggar

    2017-01-01

    Full Text Available Marfan syndrome (MFS, the founding member of connective tissue disorder, is an autosomal dominant disease; it is caused by a deficiency of the microfibrillar protein fibrillin-1 (FBN1 and characterized by involvement of three main systems; skeletal, ocular, and cardiovascular. More than one thousand mutations in FBN1 gene on chromosome 15 were found to cause MFS. Nephrotic syndrome (NS had been described in very few patients with MFS being attributed to membranoproliferative glomerulonephritis secondary to infective endocarditis. Focal segmental glomerulosclerosis (FSGS had been reported in NS in conjunction with MFS without confirming the diagnosis by mutational analysis of FBN1. We hereby present an Egyptian family with MFS documented at the molecular level; it showed a male proband with NS secondary to FSGS, unfortunately, we failed to make any causal link between FBN dysfunction and FSGS. In this context, we review the spectrum of renal involvements occurring in MFS patients.

  2. GLUCOCORTICOSTEROID THERAPY AND PHYSICAL DEVELOPMENTOF CHILDREN WITH STEROID-SENSITIVE NEPHROTIC SYNDROME: A RETROSPECTIVE STUDY

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    Olga A. Zhdanova

    2017-01-01

    Full Text Available Background. Body weight gain and growth retardation are common side effects of prolonged glucocorticosteroid  therapy in children. Time for the appearance  and elimination of glucocorticosteroid  obesity  as well as growth disorders  require further investigations.Objective.  Our aim was to study the relationship between glucocorticosteroid  therapy and changes in physical development indices of children with steroid-sensitive nephrotic syndrome (SSNS.Methods. We carried out a retrospective study of case records of patients with SSNS hospitalized in 2011–2014.  Treatment of children was carried out in accordance with the Federal Clinical Guidelines. The Z-score (ANTHRO Plus was determined for body length (height, body weight, body mass index and correlation of physical development indices with a cumulative dose and duration of glucocorticosteroid  therapy.Results.  We analyzed data on the treatment of 31 children, 18 of them received glucocorticosteroids  for 6 months (Group 1, 13 of them did not receive glucocorticosteroids       6 months (Group 2. The Z-score  of body weight in children in these groups was 1.64 ± 1.54 and 0.05 ± 1.19 (p = 0.004, Z-score  of body mass index was 1.85 ± 1.64 and -0.54 ± 1.14, respectively (p < 0.001. Excess body weight and obesity were only observed in children of Group 1 (in 6 and 9, respectively.  The Z-score  of the body length of patients in groups 1 and 2 were comparable and did not differ from normal values (0.34 ± 1.08 and 0.52 ± 1.12, respectively, p = 0.655. Correlation of Z-score values of the body length and cumulative doses of glucocorticosteroids was noted (r = -0.87, p < 0.001.Conclusion. Long-term (at least 6 months glucocorticosteroid intake is associated with the development of overweight and obesity in most children with SSNS. In patients who did not use hormonal drugs for 6 months, normal body weight values were recorded. The height of children with SSNS was within

  3. An intriguing association of Turner syndrome with severe nephrotic syndrome: searching for a diagnosis.

    Science.gov (United States)

    Minzala, G; Ismail, G

    2016-10-01

    Systemic lupus erythematosus (SLE) is a chronic disease caused by an aberrant autoimmune response, with a large spectrum of clinical manifestations. It strikingly affects women. Recent papers reveal that the men with Klinefelter syndrome (47, XXY) have a higher incidence of lupus than the men in the general population, similar with that of genotypic females. On the other hand, there is a great lack of information regarding the association of SLE with Turner syndrome, but it seems to be a lower risk for females with Turner to develop SLE. We present a rare association of a Turner syndrome with SLE, with negative immunology for SLE and with diagnosis made on renal biopsy. These data suggest that the presence of two X chromosomes may predispose to SLE, the ligand (CD40 ligand) for one of the genes that contributes to the pathogenesis of SLE being located on the X chromosome. © The Author(s) 2016.

  4. Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management.

    Science.gov (United States)

    Bierzynska, Agnieszka; McCarthy, Hugh J; Soderquest, Katrina; Sen, Ethan S; Colby, Elizabeth; Ding, Wen Y; Nabhan, Marwa M; Kerecuk, Larissa; Hegde, Shivram; Hughes, David; Marks, Stephen; Feather, Sally; Jones, Caroline; Webb, Nicholas J A; Ognjanovic, Milos; Christian, Martin; Gilbert, Rodney D; Sinha, Manish D; Lord, Graham M; Simpson, Michael; Koziell, Ania B; Welsh, Gavin I; Saleem, Moin A

    2017-04-01

    Steroid Resistant Nephrotic Syndrome (SRNS) in children and young adults has differing etiologies with monogenic disease accounting for 2.9-30% in selected series. Using whole exome sequencing we sought to stratify a national population of children with SRNS into monogenic and non-monogenic forms, and further define those groups by detailed phenotypic analysis. Pediatric patients with SRNS were identified via a national United Kingdom Renal Registry. Whole exome sequencing was performed on 187 patients, of which 12% have a positive family history with a focus on the 53 genes currently known to be associated with nephrotic syndrome. Genetic findings were correlated with individual case disease characteristics. Disease causing variants were detected in 26.2% of patients. Most often this occurred in the three most common SRNS-associated genes: NPHS1, NPHS2, and WT1 but also in 14 other genes. The genotype did not always correlate with expected phenotype since mutations in OCRL, COL4A3, and DGKE associated with specific syndromes were detected in patients with isolated renal disease. Analysis by primary/presumed compared with secondary steroid resistance found 30.8% monogenic disease in primary compared with none in secondary SRNS permitting further mechanistic stratification. Genetic SRNS progressed faster to end stage renal failure, with no documented disease recurrence post-transplantation within this cohort. Primary steroid resistance in which no gene mutation was identified had a 47.8% risk of recurrence. In this unbiased pediatric population, whole exome sequencing allowed screening of all current candidate genes. Thus, deep phenotyping combined with whole exome sequencing is an effective tool for early identification of SRNS etiology, yielding an evidence-based algorithm for clinical management. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  5. Therapy-resistant anaemia in congenital nephrotic syndrome of the Finnish type--implication of EPO, transferrin and transcobalamin losses.

    Science.gov (United States)

    Toubiana, Julie; Schlageter, Marie-Hélène; Aoun, Bilal; Dunand, Olivier; Vitkevic, Renata; Bensman, Albert; Ulinski, Tim

    2009-04-01

    Congenital nephrotic syndrome of the Finnish type (CNF) is due to NPHS1 mutation and is responsible for a variety of urinary protein losses. We report the case of a 4-month-old girl with a particularly severe form (proteinuria approximately 150 g/l) of CNF. She developed severe non-regenerative anaemia requiring bi-monthly blood transfusions despite daily EPO (600 UI/kg) and iron supplementation. Epoetin pharmacokinetics revealed a urinary loss of 27% of the given dose within the first 24 h after IV injection. However, plasma levels remained increased after 24 h (228 UI/l). Plasma transferrin and transcobalamin levels were undetectable. Atransferrinaemia and atranscobalaminaemia seem to be responsible for disturbed erythropoiesis.

  6. A case of seropositive Neuromyelitis Optica in a paediatric patient with co-existing acute nephrotic syndrome.

    Science.gov (United States)

    Volkman, Thomas; Hemingway, Cheryl

    2017-11-01

    Neuromyelitis optica (NMO) and NMO spectrum disorder (NMOSD) is a rare relapsing autoimmune disease of the central nervous system constituting less than 1% of demyelinating diseases (Jeffery and Buncic, 1996). It preferentially affects the optic nerves and spinal cord, with the brain parenchyma generally spared. Demyelinating lesions are characterised by longitudinally extensive transverse myelitis (LETM) and often longitudinally extensive optic neuritis. Following the discovery of a novel pathogenic antibody, Aquaporin 4 in 2004 (Lennon et al., 2004) this disease has been seen as a separate entity from Multiple Sclerosis (MS). We report the case of a severe AQP4 IgG case of NMO in a 10 year old child. This case unusually had a coexisting diagnosis of acute nephrotic syndrome which has only been reported once previously in the literature 2 . This article will examine some of the treatment challenges and the spectrum of co-existing autoimmune disease in NMOSD. Copyright © 2017. Published by Elsevier B.V.

  7. Successful treatment of nephrotic syndrome induced by lambda light chain deposition disease using lenalidomide: A case report and review of the literature
.

    Science.gov (United States)

    Mima, Akira; Nagahara, Dai; Tansho, Kosuke

    2018-06-01

    Light chain deposition disease (LCDD) is a monoclonal immunoglobulin deposition disease (MIDD) that is characterized by the deposition of monoclonal light chains in multiple organs, including the kidney. It is a rare disorder caused by an underlying monoclonal plasma cell dyscrasia. LCDD with renal involvement causes proteinuria, which sometimes can lead to nephrotic syndrome. The monoclonal light chains are mostly in the κ form. Treatment of LCDD is the same as that for multiple myeloma (MM); however, some conventional anticancer drugs show substantial toxicity and therefore cannot be administered to older patients or those with renal impairment. An 80-year-old woman was referred to our department with severe nephrotic syndrome (13.6 g/gCr) and anemia. A renal biopsy showed mesangial proliferation and mesangial matrix expansion, and immunohistochemistry showed positive staining for λ chains along the glomerular basement membrane, but was negative for κ chains or amyloid deposition. A bone marrow biopsy revealed 64% plasma cells. Immunoglobulin G (IgG)-λ type M protein was detected, and the levels of free λ chain was significantly increased. We concluded that her nephrotic syndrome was caused by LCDD, which resulted from IgG-λ MM. The induction of a BCD (bortezomib, cyclophosphamide, and dexamethasone) treatment regimen did not lead to a hematological response or decrease in proteinuria. The administration of combination therapy of lenalidomide and prednisolone led to the successful reduction of proteinuria and hematuria. We presented a very rare case report describing the successful treatment of LCDD (λ chain)-induced nephrotic syndrome with lenalidomide.
.

  8. Pattern of steroid resistant nephrotic syndrome in children living in the kingdom of Saudi Arabia: A single center study

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    Kari Jameela

    2009-01-01

    Full Text Available Steroid resistant nephrotic syndrome (SRNS remains a challenge facing pediatric nephrologists. The underlying histopathology usually affects the course of the disease and the response to treatment. We studied the pattern of histopathology in children with SRNS who presented to the King Abdul Aziz University Hospital (KAUH, Jeddah, Saudi Arabia. The records of all children with primary SRNS, who were seen between 2002 and 2007 were reviewed. Only patients who had undergone a renal biopsy were included in the study. The histopathology slides were reviewed by two renal pathologists independently. Patients with congenital nephrotic syndrome, lupus or sickle cell disease, were excluded from the study. Thirty-six children fulfilled the inclusion criteria, and included 25 girls and 11 boys with female to male ratio of 2.3:1. Fifty percent of the children (n=18 were Saudi and the remaining 50% were from various other racial backgrounds (9 Asians, 4 Arabs, 2 Africans and 3 from the Far East. Their mean age at presentation was 4.3 ± 3.0 years (range 1-12 years. The mean serum albumin at presentation was 15.6 ± 7.1 g/L and all of them had 4+ proteinuria on urinalysis. Five children had elevated serum creatinine at presentation while the mean serum creatinine was 50.4 ± 45.6 µmol/L. Three children had low serum complement levels at presentation and none were positive for hepatitis B surface antigen or antinuclear antibody (ANA. The renal histopathology was compatible with focal and segmental glomerulosclerosis (FSGS in 39% (n=14, IgM nephro-pathy in 28% (n=10, mesengioproliferative glomerulonephritis (MesPGN in 17% (n=6, mini-mal change disease (MCD and C1q nephropathy (C1qNP in 8% each (n=3 + 3 and IgA nephro-pathy in 3% (n=1. Our retrospective review shows that FSGS was the commonest underlying histopathology in children who presented with SRNS followed by IgM nephropathy and other variants of MCD such as MesPGN. C1qNP was the underlying cause in some

  9. Nephrotic syndrome associated with hepatointestinal schistosomiasis Síndrome nefrótica associada à esquistossomose hepatointestinal

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    H. Abensur

    1992-08-01

    Full Text Available Schistosomal nephropathy has long been related to the hepatosplenic form of schistosomiasis. In the last few years, 24 patients with hepatointestinal schistosomiasis and the nephrotic syndrome were studied. Aiming at evaluating a possible etiologic participation of schistosomiasis in the development of the nephropathy, this group was comparatively studied with a group of 37 patients with idiopathic nephrotic syndrome. Both groups had a different distribution of the histologic lesions. In the group with schistosomiasis there was a statistically significant prevalence of proliferative mesangial glomerulonephritis (33.3%, whereas in the control group there was prevalence of membranous glomerulonephritis (32.4%. On immunofluorescence, IgM was positive in 94.4% of the patients with schistosomiasis versus 55.0% in the control group (pA nefropatia esquistossomótica está classicamente vinculada à fornia hepatoesplênica da esquistossomose. Ao longo dos últimos anos 24 casos de pacientes esquistossomóticos hepato-intestinais e portadores de síndrome nefrótica foram estudados. Com o objetivo de verificar a possível participação etiológica da esquistossomose na gênese da nefropatia, analisamos este grupo comparativamente ao grupo de 37 doentes portadores de síndrome nefrótica idiopática. Ambos os grupos apresentaram distribuição distinta dos tipos histológicos de glomerulopatia. No grupo de esquistossomóticos houve predomínio estatisticamente significante de glomerulonefrite proliferativa mesangial (33.3%, enquanto no grupo controle houve predomínio da glomerulonefrite membranosa (32.4%. A positividade para IgM à imunofluorescência foi de 94.4% nos doentes esquistossomóticos versus 55.0% no grupo controle (p<0.01. No grupo de esquistossomóticos 8 pacientes evidenciaram glomerulonefrite proliferativa mesangial e 5, glomerulonefrite membranoproliferativa. Em ambos os tipos histológicos a imunofluorescência mostrou dep

  10. Vitamin D receptor gene TaqI and Apal polymorphisms and steroid responsiveness in childhood idiopathic nephrotic syndrome

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    Al-Eisa AA

    2016-08-01

    Full Text Available Amal A Al-Eisa, Mohammad Z Haider Department of Pediatrics, Faculty of Medicine, Kuwait University, Safat, Kuwait Background: Vitamin D activity is controlled by vitamin D receptors (VDRs, which are affected by different genetic polymorphisms, including TaqI and Apal restriction fragment length polymorphisms (RFLPs, which have been reported to be associated with several diseases. The aim of this study was to determine the frequency and the association of VDR gene polymorphisms with idiopathic nephrotic syndrome (INS and steroid responsiveness in Kuwaiti children. Subjects and methods: Genotypes of the VDR TaqI gene polymorphism and the Apal gene polymorphism were analyzed using polymerase chain reaction-RFLP in 78 INS patients and 56 matched controls. Results: A total of 78 INS (62 steroid sensitive [SS] and 16 steroid resistant [SR] patients with a mean age of 6.5±3.1 years were studied. Male:female ratio was 2:1. The TT genotype of VDR–TaqI polymorphism was detected in 41% of the INS patients compared to 42% of the controls (P=0.816. The heterozygous TC genotype was detected in 33% of INS patients compared to 46% of the controls (P=0.462. The CC genotype was detected in 25.6% of INS patients and 21% of the controls (P=0.719. The C-allele frequency, in its homozygous and heterozygous forms, was 71% in INS patients compared to 63% in the controls (P=0.342. Similarly, no significant difference was detected in terms of VDR–Apal polymorphism in INS patients compared to the controls for all the three genotypes (P=0.76, P=0.207, and P=0.364, respectively, for GG, GT, and TT genotypes. The T-allele frequency, in its homozygous and heterozygous forms, was 89% in INS patients compared to 93% in the controls (P=0.076. No significant difference was found in any of the allele frequencies between SS and SR subgroups when compared with each other or when compared to the controls. Conclusion: Our data do not support the use of VDR–TaqI or

  11. Elevated Urinary Levels of 8-Hydroxy-2'-deoxyguanosine in a Japanese Child of Xeroderma Pigmentosum/Cockayne Syndrome Complex with Infantile Onset of Nephrotic Syndrome.

    Science.gov (United States)

    Kondo, Daiki; Noguchi, Atsuko; Tamura, Hiroaki; Tsuchida, Satoko; Takahashi, Ikuko; Kubota, Hiroki; Yano, Tamami; Oyama, Chikako; Sawaishi, Yukio; Moriwaki, Shinichi; Takahashi, Tsutomu

    2016-07-01

    Nucleotide excision repair (NER) is an essential biological pathway protecting against ultraviolet light-induced DNA damage. Deficient NER causes a group of rare genetic disorders including two autosomal recessive diseases, xeroderma pigmentosum (XP) and Cockayne syndrome (CS). In addition to the cutaneous photosensitivity shared in XP and CS, CS is featured by growth failure, neurological deterioration, microcephaly, and deep sunken eyes. XP/CS complex is an extremely rare type of NER disorder with a distinct phenotype that is characterized by the skin and eye pathology of XP and the somatic and neurological abnormalities of CS. Some of CS cases have been reported to be complicated with renal failure, but the genetic background or the etiology of the renal failure has not been reported. We herein report a 1-year-old Japanese boy with XP/CS complex, complicated by nephrotic syndrome. Diagnosis was confirmed by the presence of compound heterozygous mutations, G47R (c.139G>A) and R616G (c.1846C>G), in the excision repair cross-complementation group 2 (ERCC2) gene. The kidney biopsies, performed at the age of 1 year and 2 months, revealed diffuse expansion of the mesangial matrix and segmental glomerulosclerosis under light microscopy, and diffused thin capillary walls with partially lamellated regions under electron microscopy. Notably, high levels of urinary 8-hydroxy-2'-deoxyguanosin, known as an oxidative stress marker, were observed during the clinical course. The patient died at the age of 1 year and 11 months because of renal failure. We suggest the involvement of oxidative stress in the pathogenesis of nephrotic syndrome in NER disorders.

  12. Low serum immunglobulin G (IgG) during nephrosis is a predictor of urinary tract infection (UTI) in children with nephrotic syndrome.

    Science.gov (United States)

    Afroz, S; Roy, D K; Khan, A H

    2013-04-01

    Low serum level of IgG, complement C3 and C4 in nephrotic syndrome children may cause increased susceptibility to infection. Serum level of IgG and complements in nephrotic children (NS) with UTI has been analyzed in this cross sectional study. It was carried out in the department of Pediatric nephrology, National Institute of Kidney Diseases & Urology (NIKDU), Dhaka, Bangladesh. The study subjects were followed up prospectively for one year to see and compare the frequency of relapse of NS and UTI. Patients were selected in a nonrandom purposive technique. Nephrotic syndrome children with initial attack between 1-12 year of age were included over a period of one year. The patients were grouped into Group I - UTI positive and Group II - UTI negative depending on urine culture positivity and colony count >10⁵ CFU/ml. Serum IgG and complements C3, C4 levels were done in both groups during nephrosis and were compared. A total of 101 children M: F 1.7:1, mean age 5.96±3.2 years were included in this study. Group I, n=45 vs. Group II, n=56. The mean serum level of IgG was low in Group I (549.91±210.71 vs. 728.64±235.81mg/dl, pUTI in nephrotic children. Higher number of children in Group II were at remission (n=24) during follow up, while frequent relapsers were high in Group I (n=22). Increased frequency of UTI attack (88 episodes) was found in Group I children compared to none in Group II during follow up. So low serum level of IgG in children with NS during nephrosis can predict UTI with an odds ratio of 6.63 as well as relapse. Serum level of C3, C4 do not associated with any risk of development of UTI in NS children.

  13. Serum and urinary lipoproteins in the human nephrotic syndrome: evidence for renal catabolism of lipoproteins

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    Shore, V.G.; Forte, T.; Licht, H.; Lewis, S.B.

    1982-03-01

    The urinary excretion of lipoproteins and the possibility of catabolic alterations on glomerular filtration were investigated in four nephrotic subjects difering in etiology, serum lipoprotein profile, and 24 hr urinary output of protein and lipids. The apolipoproteins and lipoproteins of urine were compared with those of serum with respect to distribution profile, physical properties, and composition. As expected from molecular sieving effects during glomerular filtration, the urinary HDL were more abundant than the lower density lipoproteins even when the plasma LDL was elevated markedly. Intact apolipoproteins were not found in the concentrated urinary fraction isolated by ultrafiltration between the limits of 10/sup 4/ and 5 x 10/sup 4/ daltons. On the basis of immunoreactivity, gel electrophoresis, and amino acid composition, apolipoproteins B and AI are the major and minor proteins, respectively, of urinary LDL, and apo B is the major protein of the urinary IDL and VLDL. Apolipoproteins AI, AII, CI, CIII, and possibly AIV were isolated from the urinary HDL. As much as 20% of the protein moiety of the urinary HDL appeared to be large apolipoprotien fragments with molecular weights and isoelectric points similar to those of apo CII and apo CIII. The lower density classes of urinary lipoproteins also appeared to have lost apo E and apo C's and to have undergone partial proteolysis.

  14. Mesenchymal Stem Cells May Ameliorate Nephrotic Syndrome Post-Allogeneic Hematopoietic Stem Cell Transplantation-Case Report

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    Xin Zhang

    2017-08-01

    Full Text Available IntroductionBecause of their immunomodulatory and anti-inflammatory effects, mesenchymal stem cells (MSCs have been considered as potential therapeutic agents for treating immune-related or autoimmune diseases, such as graft-versus-host disease (GVHD. Nephrotic syndrome (NS after allogeneic hematopoietic stem cell transplantation (allo-HSCT is an uncommon complication with unclear etiology and pathogenesis. It may be an immune disorder involving immune complex deposition, B cells, regulatory T cells (Tregs, and Th1 cytokines and be a manifestation of chronic GVHD. Corticosteroids and calcium antagonists, alone or in combination, are the most common therapeutic agents in this setting. Rituximab is commonly administered as salvage treatment. However, treatment failure and progressive renal function deterioration has been reported to occur in approximately 20% of patients in a particular cohort.Case presentationWe present a patient who developed NS 10 months after allo-HSCT. After treatment failure with cyclosporine A, prednisone, and rituximab, she achieved a complete response with MSC treatment. The clinical improvement of this patient was accompanied by a decreased B cell population together with an increased frequency of regulatory B cells (Bregs and Tregs after MSC treatment.ConclusionMSCs could modulate NS after allo-HSCT by suppressing B cell proliferation, inducing Tregs and Bregs, and inhibiting inflammatory cytokine production by monocytes and NK cells. Among all these, Bregs might play an important role in ameliorating the NS of this patient.

  15. Association of neutrophil gelatinase associated lipocalin and cystatin-c with kidney function in children with nephrotic syndrome

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    Alaleh Gheissari

    2013-01-01

    Full Text Available Background: Nephrotic syndrome (NS is a major clinical concern in human health, especially in children. Despite of the etiology, the prediction of remission in different treatment regimens based on suitable biomarkers is under development. The goal of this evaluation was the demonstration of correlation between serum level of Neutrophil gelatinase associated lipocalin (NGAL and cystatin-C with kidney function in patients with NS. Methods: During the period between September 2008 and December 2011, 52 patients admitted to St. Al Zahra University Hospital were selected for evaluation. The measured parameters consisted of NGAL, cystatin-C, creatinine, albumin, blood urea nitrogen, urine protein, glomerular filtration rate. Demographic data were collected and considered in comparisons. Comparison between variables and their correlations were examined. Results: Means of serum NGAL and cystatin-C were significantly higher in case than the control group, P < 0.05. The mean of serum NGAL in patients without remission and who achieved remission were 23.09 (standard deviation [SD] ±10.11 and 36.26 (SD ± 20.10 ng/ml respectively; P < 0.05. Serum NGAL levels had a correlation with the following factors: Systolic blood pressure, diastolic blood pressure (DBP, cystatin-C, remission. Linear regression analysis showed a significant correlation between cystatin-C and systolic and DBP. Conclusions: Based on the results, serum NGAL can be used as a prognostic marker for remission. In addition, NGAL and cystatin-C are biomarkers of kidney injury in NS.

  16. The significance of determination of renal tubular markers before and after treatment in the primary nephrotic syndrome

    International Nuclear Information System (INIS)

    Xie Bing; Jiang Liping

    2011-01-01

    Objective: To evaluate the damage of renal tubule of patients with primary nephrotic syndrome (PNS) by detecting renal tubule markers and investigate the significance of different therapeutic effects. Methods: Serum levels of interleukin-6(IL-6), ET-1, α 1 -microglobulin(α 1 -m), β 2 -microglobulin(β 2 -m) and plasma level of ET-1 were determined with RIA, fibrinogen degradation product (FDP) with ELISA, automatic biochemistry analysis N-acetyl-β-D-glucosaminidase(NAG), CH 2 O was determined with physico-method respectively. Results: The concentrations of IL-6, ET-1, α 1 -m, β 2 -m, FDP, NAG were significantly decreased in cases of complete remission after therapy (P 2 O excepted (P>0.05), the decrease of IL-6, ET-1, α 1 -m, FDP were no significant in cases of invalid (P>0.05), the concentrations of renal tubule markers in cases of partial remission and invalid were higher than those in cases of complete and significant remission. Conclusion: The determination of several renal tubule markers can be used for diagnose, monitor and judge the therapeutic effects of PNS. (authors)

  17. Association of ACE and MDR1 Gene Polymorphisms with Steroid Resistance in Children with Idiopathic Nephrotic Syndrome.

    Science.gov (United States)

    Dhandapani, Mohanapriya Chinambedu; Venkatesan, Vettriselvi; Rengaswamy, Nammalwar Bollam; Gowrishankar, Kalpana; Nageswaran, Prahlad; Perumal, Venkatachalam

    2015-08-01

    The purpose of the study was to investigate the distribution of insertion/deletion (I/D) polymorphisms of the angiotensin-converting enzyme (ACE) gene and three exonic polymorphisms of the multidrug resistance 1 (MDR1) gene (C3435T, C1236T, and G2677T) in children diagnosed with idiopathic nephrotic syndrome (INS). The study group consisted of 100 healthy controls and 150 INS patients, of which 50 were steroid resistant. Genomic DNA from blood samples was isolated from both of these groups and genotyping of the ACE and MDR1 genes was performed by polymerase chain reaction (PCR) using specific primers. There was no significant difference observed in the genotypic distribution and D allele frequency of the ACE gene. The two single-nucleotide polymorphisms (SNPs), C1236T and C3435T, of the MDR1 gene showed no significance, whereas the SNP G2677T/A was significantly associated with the genotypes GT and GA of the MDR1 gene, indicating it may be a potential marker to detect drug resistance. Screening these polymorphisms will pave the way to better understand the molecular mechanisms of the disease, which may be useful in developing targeted therapies for INS patients.

  18. Impact of the 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene on primary nephrotic syndrome.

    Science.gov (United States)

    Luo, Yuezhong; Wang, Chao; Tu, Haitao

    2014-03-01

    The aim of the present study was to investigate whether the four guanosines (4G)/five guanosines (5G) polymorphism in the gene coding for plasminogen activator inhibitor-1 (PAI-1) affects the clinical features of primary nephrotic syndrome (PNS). A cohort of 200 biopsy-diagnosed PNS patients was studied, with 40 healthy subjects as controls. The PAI-1 gene polymorphism was detected by polymerase chain reaction and DNA sequencing. Associations between the PAI-1 4G/5G polymorphism and clinical features and pathological types of PNS were analyzed. The results indicated that the PAI-1 genotype distribution is significantly different between patients with PNS and healthy controls, with significantly higher numbers of the 4G/4G genotype and lower numbers of the 5G5G genotype detected in PNS patients compared to controls (both P5G genotypes, as well as of the 4G allele. The increased 4G frequency was also detected in patients with minimal change disease (MCD). Significantly increased international normalized ratio (INR) and prolonged activated partial thromboplastin time (APTT) were observed in 4G/4G compared to 5G/5G PNS subjects. The response to steroids was not significantly different among the three genotypes. In conclusion, the 4G allele of the PAI-1 gene appears to be associated with PNS, especially in MN and IgAN patients. These findings suggest that specific targeting may be required for the treatment of PNS patients with the 4G/4G genotype.

  19. DD genotype of ACE gene in boys: may it be a risk factor for minimal change nephrotic syndrome?

    Science.gov (United States)

    Alasehirli, Belgin; Balat, Ayşe; Büyükçelik, Mithat

    2012-01-01

    It has been shown that angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism affects the circulating and cellular levels of ACE and may be a risk factor in several renal diseases. We analyzed the association of ACE gene I/D polymorphism with the clinical presentation of minimal change nephrotic syndrome (MCNS) in a Turkish child population. This study consisted of 97 children with MCNS and 144 healthy controls. Genotyping of ACE gene was performed using polymerase chain reaction (PCR). The distributions of ACE genotypes were II in 13%, ID in 49%, and DD in 38% in patient group, and 9%, 49%, and 42% in control group, respectively. The frequency of the D allele was 63% and that of the I allele was 37% in patients. There were no relevant differences in the allele frequencies and genotypes of ACE I/D polymorphism between patients and controls. However, DD genotype was higher in boys in children with MCNS (78.4%. vs. 50.0%, p = 0.004). The frequencies of DD genotype and D allele in boys were 7.25 and 2.56 times higher than II genotype and I allele in the patient group, respectively. We suggest that DD genotype in boys may be one of the risk factors for MCNS.

  20. Opiate v CNS depressant therapy in neonatal drug abstinence syndrome.

    Science.gov (United States)

    Kandall, S R; Doberczak, T M; Mauer, K R; Strashun, R H; Korts, D C

    1983-04-01

    Paregoric and phenobarbital, administered randomly in 153 passively addicted neonates, initially appeared to control neonatal abstinence signs equally well. However, seven of the 62 phenobarbital-treated newborns had abstinence-associated seizures within the first month of life, while none of 49 paregoric-treated neonates had seizures. Forty-two neonates initially requiring no specific pharmacotherapy for abstinence signs were born to mothers taking less methadone hydrochloride just before delivery. Five of those 42 neonates, however, had seizures within the first 14 days of life. Seizure occurrence could not be predicted from analysis of early abstinence patterns. We consider paregoric to be the treatment of choice for the neonatal abstinence syndrome. Phenobarbital use should be monitored with serum drug levels and modification of recommended dosage regimens considered.

  1. ACE I/D Gene Polymorphism Can't Predict the Steroid Responsiveness in Asian Children with Idiopathic Nephrotic Syndrome: A Meta-Analysis

    Science.gov (United States)

    Su, Li-Na; Lei, Feng-Ying; Huang, Wei-Fang; Zhao, Yan-Jun

    2011-01-01

    Background The results from the published studies on the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and the treatment response to steroid in Asian children with idiopathic nephrotic syndrome (INS) is still conflicting. This meta-analysis was performed to evaluate the relation between ACE I/D gene polymorphism and treatment response to steroid in Asian children and to explore whether ACE D allele or DD genotype could become a predictive marker for steroid responsiveness. Methodology/Principal Findings Association studies were identified from the databases of PubMed, Embase, Cochrane Library and CBM-disc (China Biological Medicine Database) as of September 1, 2010, and eligible investigations were synthesized using meta-analysis method. Five investigations were identified for the analysis of association between ACE I/D gene polymorphism and steroid-resistant nephrotic syndrome (SRNS) risk in Asian children and seven studies were included to explore the relationship between ACE I/D gene polymorphism and steroid-sensitive nephrotic syndrome (SSNS) susceptibility. Five investigations were recruited to explore the difference of ACE I/D gene distribution between SRNS and SSNS. There was no a markedly association between D allele or DD genotype and SRNS susceptibility or SSNS risk, and the gene distribution differences of ACE between SRNS and SSNS were not statistically significant. II genotype might play a positive role against SRNS onset but not for SSNS (OR = 0.51, P = 0.02; OR = 0.95, P = 0.85; respectively), however, the result for the association of II genotype with SRNS risk was not stable. Conclusions/Significance Our results indicate that D allele or DD homozygous can't become a significant genetic molecular marker to predict the treatment response to steroid in Asian children with INS. PMID:21611163

  2. Abdominal complications in black and Indian children with nephrotic ...

    African Journals Online (AJOL)

    Abdominal complications were detected and investigated in 19 (10%) of 191 children with nephrotic syndrome who experienced 35 episodes of these complications. Fourteen children were Indian with steroid-responsive nephrotic syndrome, and 5 were black, of whom 4 had membranous nephropathy and 1 focal ...

  3. Acid-base disturbances in nephrotic syndrome: analysis using the CO2/HCO3 method (traditional Boston model) and the physicochemical method (Stewart model).

    Science.gov (United States)

    Kasagi, Tomomichi; Imai, Hirokazu; Miura, Naoto; Suzuki, Keisuke; Yoshino, Masabumi; Nobata, Hironobu; Nagai, Takuhito; Banno, Shogo

    2017-10-01

    The Stewart model for analyzing acid-base disturbances emphasizes serum albumin levels, which are ignored in the traditional Boston model. We compared data derived using the Stewart model to those using the Boston model in patients with nephrotic syndrome. Twenty-nine patients with nephrotic syndrome and six patients without urinary protein or acid-base disturbances provided blood and urine samples for analysis that included routine biochemical and arterial blood gas tests, plasma renin activity, and aldosterone. The total concentration of non-volatile weak acids (A TOT ), apparent strong ion difference (SIDa), effective strong ion difference (SIDe), and strong ion gap (SIG) were calculated according to the formulas of Agrafiotis in the Stewart model. According to the Boston model, 25 of 29 patients (90%) had alkalemia. Eighteen patients had respiratory alkalosis, 11 had metabolic alkalosis, and 4 had both conditions. Only three patients had hyperreninemic hyperaldosteronism. The Stewart model demonstrated respiratory alkalosis based on decreased PaCO 2 , metabolic alkalosis based on decreased A TOT , and metabolic acidosis based on decreased SIDa. We could diagnose metabolic alkalosis or acidosis with a normal anion gap after comparing delta A TOT [(14.09 - measured A TOT ) or (11.77 - 2.64 × Alb (g/dL))] and delta SIDa [(42.7 - measured SIDa) or (42.7 - (Na + K - Cl)]). We could also identify metabolic acidosis with an increased anion gap using SIG > 7.0 (SIG = 0.9463 × corrected anion gap-8.1956). Patients with nephrotic syndrome had primary respiratory alkalosis, decreased A TOT due to hypoalbuminemia (power to metabolic alkalosis), and decreased levels of SIDa (power to metabolic acidosis). We could detect metabolic acidosis with an increased anion gap by calculating SIG. The Stewart model in combination with the Boston model facilitates the analysis of complex acid-base disturbances in nephrotic syndrome.

  4. Mutations in COQ8B (ADCK4) found in patients with steroid-resistant nephrotic syndrome alter COQ8B function

    OpenAIRE

    Fonseca, Luis Vazquez; Doimo, Mara; Calderan, Cristina; Desbats, Maria Andrea; Acosta, Manuel J.; Cerqua, Cristina; Cassina, Matteo; Ashraf, Shazia; Hildebrandt, Friedhelm; Sartori, Geppo; Navas, Placido; Trevisson, Eva; Salviati, Leonardo

    2018-01-01

    Abstract Mutations in COQ8B cause steroid‐resistant nephrotic syndrome with variable neurological involvement. In yeast, COQ8 encodes a protein required for coenzyme Q (CoQ) biosynthesis, whose precise role is not clear. Humans harbor two paralog genes: COQ8A and COQ8B (previously termed ADCK3 and ADCK4). We have found that COQ8B is a mitochondrial matrix protein peripherally associated with the inner membrane. COQ8B can complement a ΔCOQ8 yeast strain when its mitochondrial targeting sequenc...

  5. CNS changes in Usher's syndrome with mental disorder: CT, MRI and PET findings.

    Science.gov (United States)

    Koizumi, J; Ofuku, K; Sakuma, K; Shiraishi, H; Iio, M; Nawano, S

    1988-01-01

    CNS changes in a case of Usher's syndrome associated with schizophrenia-like mental disorder were observed by CT, MRI and PET. The neuro-radiological findings of the case demonstrate the degenerative and metabolic alterations in various regions of cortex, white matter and subcortical areas in the brain. Mental disorder of the case is almost indistinguishable from that of schizophrenia, but the psychotic feature is regarded as an atypical or mixed organic brain syndrome according to the classification in the third edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-III). Images PMID:3264568

  6. Angiotensin-converting enzyme genotype is not a significant genetic risk factor for idiopathic nephrotic syndrome in Croatian children.

    Science.gov (United States)

    Batinić, Danko; Sertić, Jadranka; Ćorić, Marijana; Konjevoda, Paško; Batinić, Danica; Milošević, Danko

    2015-01-01

    The association of the angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with idiopathic nephrotic syndrome (INS) is controversial. Only scarce information on European populations is available. The aim of the study was to investigate the distribution of the ACE gene I/D polymorphism and its impact on INS in children from Croatia. Ninety-five children with INS were investigated: 30 with minimal change disease (MCD), 35 with mesangial proliferative glomerulonephritis (MesPGN) and 30 with focal segmental glomerulosclerosis (FSGS). The control group consisted of 73 healthy adults. ACE gene was analyzed using the PCR method. The results were correlated with clinical features, renal morphology and response to immunosuppresive therapy. There was no correlation of ACE genotype with gender, age of the disease onset, level of proteinuria, presence of hematuria or hypertension, and GFR at onset of the disease. No statistically significant differences in ACE genotype or allele frequencies between the controls and whole group of patients, MCD group, MesPGN group, FSGS group, steroid sensitive (SS) patients, steroid resistant (SR) patients, as well as each other, were found, although DD genotype tended to be more frequent in FSGS patients, SR patients, and frequent relapsers. Among 11 children treated with cyclophosphamide the D allele was significantly higher among non-responders (p = 0.003). DD genotype is not a genetic risk factor for acquiring INS nor significant phenotype modifier regarding to clinical and pathohistological picture and response to steroids in Croatian children. The potential application of ACE genotyping in predicting cyclophosphamide response deserves further investigation. © 2015 S. Karger AG, Basel.

  7. Clinical value of NPHS2 analysis in early- and adult-onset steroid-resistant nephrotic syndrome.

    Science.gov (United States)

    Santín, Sheila; Tazón-Vega, Bárbara; Silva, Irene; Cobo, María Ángeles; Giménez, Isabel; Ruíz, Patricia; García-Maset, Rafael; Ballarín, José; Torra, Roser; Ars, Elisabet

    2011-02-01

    To date, very few cases with adult-onset focal segmental glomerulosclerosis (FSGS) carrying NPHS2 variants have been described, all of them being compound heterozygous for the p.R229Q variant and one pathogenic mutation. Mutation analysis was performed in 148 unrelated Spanish patients, of whom 50 presented with FSGS after 18 years of age. Pathogenicity of amino acid substitutions was evaluated through an in silico scoring system. Haplotype analysis was carried out using NPHS2 single nucleotide polymorphism and microsatellite markers. Compound heterozygous or homozygous NPHS2 pathogenic mutations were identified in seven childhood-onset steroid-resistant nephrotic syndrome (SRNS) cases. Six additional cases with late childhood- and adult-onset SRNS were compound heterozygotes for p.R229Q and one pathogenic mutation, mostly p.A284V. p.R229Q was more frequent among SRNS cases relative to controls (odds ratio=2.65; P=0.02). Significantly higher age at onset of the disease and slower progression to ESRD were found in patients with one pathogenic mutation plus the p.R229Q variant in respect to patients with two NPHS2 pathogenic mutations. NPHS2 analysis has a clinical value in both childhood- and adult-onset SRNS patients. For adult-onset patients, the first step should be screening for p.R229Q and, if positive, for p.A284V. These alleles are present in conserved haplotypes, suggesting a common origin for these substitutions. Patients carrying this specific NPHS2 allele combination did not respond to corticoids or immunosuppressors and showed FSGS, average 8-year progression to ESRD, and low risk for recurrence of FSGS after kidney transplant.

  8. Clinical Features and Long-Term Outcome of Nephrotic Syndrome Associated with Heterozygous NPHS1 and NPHS2 Mutations

    Science.gov (United States)

    Caridi, Gianluca; Gigante, Maddalena; Ravani, Pietro; Trivelli, Antonella; Barbano, Giancarlo; Scolari, Francesco; Dagnino, Monica; Murer, Luisa; Murtas, Corrado; Edefonti, Alberto; Allegri, Landino; Amore, Alessandro; Coppo, Rosanna; Emma, Francesco; De Palo, Tommaso; Penza, Rosa; Gesualdo, Loreto; Ghiggeri, Gian Marco

    2009-01-01

    Background and objectives: Mutations in nephrin (NPHS1) and podocin (NPHS2) genes represent a major cause of idiopathic nephrotic syndrome (NS) in children. It is not yet clear whether the presence of a single mutation acts as a modifier of the clinical course of NS. Design, setting, participants, & measurements: We reviewed the clinical features of 40 patients with NS associated with heterozygous mutations or variants in NPHS1 (n = 7) or NPHS2 (n = 33). Long-term renal survival probabilities were compared with those of a concurrent cohort with idiopathic NS. Results: Patients with a single mutation in NPHS1 received a diagnosis before those with potentially nongenetic NS and had a good response to therapies. Renal function was normal in all cases. For NPHS2, six patients had single heterozygous mutations, six had a p.P20L variant, and 21 had a p.R229Q variant. Age at diagnosis and the response to drugs were comparable in all NS subgroups. Overall, they had similar renal survival probabilities as non-NPHS1/NPHS2 cases (log-rank χ2 0.84, P = 0.656) that decreased in presence of resistance to therapy (P < 0.001) and in cases with renal lesions of glomerulosclerosis and IgM deposition (P < 0.001). Cox regression confirmed that the only significant predictor of dialysis was resistance to therapy. Conclusions: Our data indicate that single mutation or variant in NPHS1 and NPHS2 does not modify the outcome of primary NS. These patients should be treated following consolidated schemes and have good chances for a good long-term outcome. PMID:19406966

  9. Cerebral sinovenous thrombosis in a nephrotic child

    Directory of Open Access Journals (Sweden)

    Rodrigues Marcelo Masruha

    2003-01-01

    Full Text Available Nephrotic syndrome in infancy and childhood is known to be associated with a hypercoagulable state and thromboembolic complications, but cerebral sinovenous thrombosis (CST is a very rare and serious one, with only a few isolated reports in the literature. A case is presented of a 9-year-old boy with nephrotic syndrome that acutely developed signs and symptoms of intracranial hypertension syndrome. CST was diagnosed on cranial CT and MRI and he gradually recovered after treatment with anticoagulants. The diagnosis of CST should be considered in any patient with nephrotic syndrome who develops neurologic symptoms. The discussion of this case, coupled with a review of the literature, emphasizes that early diagnosis is essential for institution of anticoagulation therapy and a successful outcome. This report also illustrates the difficulties that may be encountered in managing such a patient.

  10. Structural characterization and mutational assessment of podocin - a novel drug target to nephrotic syndrome - an in silico approach.

    Science.gov (United States)

    Tabassum, Asra; Rajeshwari, Tadigadapa; Soni, Nidhi; Raju, D S B; Yadav, Mukesh; Nayarisseri, Anuraj; Jahan, Parveen

    2014-03-01

    Non-synonymous single nucleotide changes (nSNC) are coding variants that introduce amino acid changes in their corresponding proteins. They can affect protein function; they are believed to have the largest impact on human health compared with SNCs in other regions of the genome. Such a sequence alteration directly affects their structural stability through conformational changes. Presence of these conformational changes near catalytic site or active site may alter protein function and as a consequence receptor-ligand complex interactions. The present investigation includes assessment of human podocin mutations (G92C, P118L, R138Q, and D160G) on its structure. Podocin is an important glomerular integral membrane protein thought to play a key role in steroid resistant nephrotic syndrome. Podocin has a hairpin like structure with 383 amino acids, it is an integral protein homologous to stomatin, and acts as a molecular link in a stretch-sensitive system. We modeled 3D structure of podocin by means of Modeller and validated via PROCHECK to get a Ramachandran plot (88.5% in most favored region), main chain, side chain, bad contacts, gauche and pooled standard deviation. Further, a protein engineering tool Triton was used to induce mutagenesis corresponding to four variants G92C, P118L, R138Q and D160G in the wild type. Perusal of energies of wild and mutated type of podocin structures confirmed that mutated structures were thermodynamically more stable than wild type and therefore biological events favored synthesis of mutated forms of podocin than wild type. As a conclusive part, two mutations G92C (-8179.272 kJ/mol) and P118L (-8136.685 kJ/mol) are more stable and probable to take place in podocin structure over wild podocin structure (-8105.622 kJ/mol). Though there is lesser difference in mutated and wild type (approximately, 74 and 35 kJ/mol), it may play a crucial role in deciding why mutations are favored and occur at the genetic level.

  11. BRAINSTEM AUDITORY EVOKED POTENTIAL AS AN INDEX OF CNS DEMYELINATION IN GUILLAIN -BARRÉ SYNDROME (GBS

    Directory of Open Access Journals (Sweden)

    Smita Singh

    2016-01-01

    Full Text Available Background: Guillain-Barré Syndrome (GBS is an acute, frequently severe and fulminant polyradicular neuropathy that is autoimmune in nature. GBS manifest as rapidly evolving areflexic motor paralysis with or without sensory disturbances. It mainly involves peripheral nervous system and autonomic nervous system. There are rare evidences about the involvement of central nervous system (CNS in GBS. Aims: The main objective of the study was to assess the CNS involvement in GBS using the Brainstem Auditory Evoked Potential (BAEP. Methods & Material: The study was conducted in the clinical neurophysiology lab in the department of physiology, CSMMU Lucknow. Study group involved 26 subjects (n=26 having GBS and control group involved 30 normal subjects (n=30. BAEPS were recorded by Neuroperfect- EMG 2000 EMG/NCV/EPsytem. The data so obtained were subjected to analysis using Statistical Package for Social Sciences (SPSS Version 13.0. Results & Conclusions: There was significant increase in PIII & PV peak latencies and PI-PIII & PI-PV interpeak latencies in both left and right ear in the study group, which showed the CNS involvement in GBS which can be assessed using BAEP.

  12. [Expression of glomerular heparan sulfate domains in pediatric patients with minimal change nephrotic syndrome].

    Science.gov (United States)

    Dong, Li-Qun; Wang, Zheng; Yu, Ping; Guo, Yan-Nan; Wu, Jin; Feng, Shi-Pin; Li, Sha

    2009-01-01

    To investigate the expression of glomerular heparin sulfate (HS) in paediatric patients with minimal change nephritic syndrome (MCNS). The kidyney tissues were collected by biopsy from 13 paediatric patients with MCNS, while 5 normal renal biopsy samples were used as control. HS in glomeruli was analysed by indirect immunofluorescence staining using four different monoclonal antibodies, Hepss1, 3G10, JM403 and 10E4, which all recognize distinct HS species and each interacts with a specific HS domain. The concentrations of urine heparan sulfate also were measured by enzyme-linked immunosorbent assay (Elisa). Expression of HS fine domains was aberrant in paediatric patients compared with control subjects. Children with MCNS in replase showed a decreased glomerular expression of 10E4, JM403 and Hepss1 (P peadiatric patients with MCNS when compared with that in control subjects (P < 0.01). These results suggest that loss of heparan sulphate in renal tissue may play a role in the pathogenesis of MCNS proteinuria.

  13. [Effect of Low Molecular Weight Heparin Calcium Combined Compound Danshen Injection on Perinatal Outcomes of Nephrotic Syndrome Patients with Early Onset Severe Pre-eclampsia].

    Science.gov (United States)

    Tong, Chong-xin; Xing, Xiao-fen; Qiao, Shu-hua; Liu, Lin; Shan, Ling

    2015-08-01

    To observe the effect of low molecular weight heparin calcium (LMWHC) combined Compound Danshen Injection (DI) on nephrotic syndrome patients with early onset severe preeclampsia. Totally 80 nephrotic syndrome patients with early onset severe pre-eclampsia were randomly assigned to four groups voluntarily, i.e., Group A (22 cases, treated by magnesium sulfate), B (19 cases, treated by magnesium sulfate plus LMWHC), C (21 cases, magnesium sulfate plus DI), D (18 cases, magnesium sulfate plus LMWHC and DI). Umbilical arterial S/D ratios, amniotic fluid index (AFI), prolonged gestational age, placenta weight, neonatal weight, and Apgar score were compared among the four groups. Compared with before treatment in the same group, umbilical arterial S/D ratios decreased in the four groups (P <0. 05). AFI decreased in Group A, while it increased in Group B, C, and D (P<0. 05). Compared with Group A at the same time point, umbilical arterial S/D ratios decreased, and AFI increased in Group B, C, and D (P <0. 01 , P <0. 05). Prolonged gestational age and neonatal weight were increased in Group B, C, and D (P <0. 01, P <0. 05). Placenta weight were increased in Group B and D (P <0. 05). Apgar scores at 1 and 5 min were improved in Group D (P <0. 05). Compared with Group B and C at the same time point, umbilical arterial S/D ratios decreased, and AFI increased in Group D (P<0. 05). Compared with Group B, prolonged gestational age and placenta weight were decreased in Group C, but prolonged gestational age and placenta weight were increased in Group D (P <0.05). Compared with Group C, prolonged gestational age, placenta weight, and neonatal weight were increased in Group D (P <0. 05). Treatment of nephrotic syndrome patients with early onset severe pre-eclampsia by LMWHC combined DI could prolong gestational ages, obviously improve prenatal outcomes, with better effect obtained than using any of them alone.

  14. Increased VLDL in nephrotic patients results from a decreased catabolism while increased LDL results from increased synthesis

    NARCIS (Netherlands)

    de Sain-van der Velden, M; Kaysen, GA; Barrett, HA; Stellaard, F; Gadellaa, MM; Voorbij, HA; Reijngoud, DJ; Rabelink, TJ

    Increased very low density lipoprotein (VLDL) in nephrotic patients results from a decreased catabolism while increased low density lipoprotein (LDL) results from increased synthesis. Hyperlipidemias a hallmark of nephrotic syndrome that has been associated with increased risk for ischemic heart

  15. A case of rheumatic fever with acute post-streptococcal glomerulonephritis and nephrotic syndrome caused by a cutaneous infection with beta-hemolytic streptococci

    Directory of Open Access Journals (Sweden)

    Carsten Sauer Mikkelsen

    2010-01-01

    Full Text Available A middle-aged patient of Greenlandic origin was referred for skin infection of the leg. An initial minor trauma of the skin of the distal right lower extremity was complicated by bullous erysipelas which cultured positive for group A β-hemolytic streptococci (GABHS. The clinical condition deteriorated and necrotizing fasciitis developed despite relevant surgical and antibiotic treatment. Approximately 3 weeks later, the patient developed arthralgia, impaired renal function with azotemia, hypertension and severe nephrotic syndrome with periorbital and peripheral edema. A kidney biopsy demonstrated endocapillary glomerulonephritis. Concomitantly, carditis with chest pain, moderately reduced left ventricular ejection fraction and mitral regurgitation were noted. The patient had no signs of pharyngitis in the whole period. The patient thus contracted poststreptococ glomerulonephritis and furthermore she fulfilled the criteria of acute rheumatic fever following a GABHS skin infection. We suggest a possible relation between a virulent GABHS clone causing NF and ARF.

  16. Acute kidney injury in idiopathic nephrotic syndrome of childhood is a major risk factor for the development of chronic kidney disease.

    Science.gov (United States)

    Yaseen, Afshan; Tresa, Vina; Lanewala, Ali Asghar; Hashmi, Seema; Ali, Irshad; Khatri, Sabeeta; Mubarak, Muhammed

    2017-11-01

    Acute kidney injury (AKI) is an important complication of idiopathic nephrotic syndrome (INS) and is associated with adverse outcomes, especially the development of chronic kidney disease (CKD). We aimed to determine the clinical profile of children with INS who developed AKI and its short-term outcome. This prospective study was conducted from March 2014 to October 2015. A total of 119 children of INS (age: 2-18 years) fulfilling the pediatric RIFLE criteria for the diagnosis of AKI were enrolled and followed up for 3 months to determine the outcome. Factors predisposing to CKD were studied. The mean age at presentation was 8.8 ± 3.59 years and males were 74 (62.2%). At presentation, 61 (51.3%) children were in Risk category, 43 (36.1%) in Injury category, and 15 (12.6%) in Failure category. Most of them (41.2%) had steroid-resistant nephrotic syndrome (SRNS) and focal segmental glomerulosclerosis (FSGS) on histopathology (33.6%). Infections were the major predisposing factor for AKI in 67 (56.3%) cases. Drug toxicity was the next common, found in 52 (43.7%) children. A total of 65 (54.6%) children recovered from AKI, while 54 (45.4%) did not. CKD developed in 49 (41.2%) non-recovered cases and 5 (4.2%) children succumbed to acute illness. SRNS, cyclosporine use, FSGS on histology, and drug toxicity were significant factors associated with the development of CKD. AKI associated with INS is a reversible condition in most cases but it can progress to CKD, especially among those who have SRNS, FSGS, and drug toxicity.

  17. Nephrotic Syndrome in Adults

    Science.gov (United States)

    ... Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información ... Kidney Disease Weight Management Liver Disease Urologic Diseases Endocrine Diseases Diet & Nutrition Blood Diseases Diagnostic Tests La información ...

  18. Childhood Nephrotic Syndrome

    Science.gov (United States)

    ... or technician places a strip of chemically treated paper, called a dipstick, into the child’s urine sample. Patches on the dipstick change color when albumin is present in urine. Urine albumin-to-creatinine ...

  19. [Spectrum and drug sensitivity of pathogenic bacteria in children with nephrotic syndrome complicated by urinary tract infection: an analysis of 97 cases].

    Science.gov (United States)

    Song, Shao-Na; Zhang, Bi-Li; Wang, Wen-Hong; Zhang, Xuan

    2012-09-01

    To investigate the spectrum and drug sensitivity of pathogenic bacteria in children with nephrotic syndrome (NS) complicated by urinary tract infection (UTI). A retrospective analysis was performed on the spectrum and drug sensitivity of pathogenic bacteria in 97 children with NS complicated by UTI, who hospitalized from January to December, 2011. The incidence of UTI in children with NS was 36.5%. It was significantly more common in children with recurrent NS than in those with primary NS (44.0% vs 31.9%; Ppathogenic bacteria (50.5%), including Enterococcus faecium (29.4%) and Enterococcus faecalis (21.1%), followed by Gram-negative bacteria, such as Escherichia coli (15.6%) and Klebsiella pneumoniae (14.7%). Enterococcus was highly sensitive to nitrofurantoin, vacomycin and linezolid, but was highly resistant to tetracycline and moxifloxacin. More multi-resistant strains were detected in Enterococcus faecium than in Enterococcus faecalis (72% vs 17%; Pbacteria, 25% produced extended spectrum β-lactamases (ESBLs). ESBLs-producing bacteria had 100% sensitivity to imipenem, amikacin and piperacillin/tazobactam but were highly resistant to ampicillin, cefazolin and ceftriaxone. Children with recurrent NS are more susceptible to UTI than those with primary NS. Enterococcus is becoming major pathogenic bacteria for UTI in children with NS and has relatively high drug resistance, and most strains of Enterococcus faecium are multi-resistant.

  20. Mutations in COQ8B (ADCK4) found in patients with steroid‐resistant nephrotic syndrome alter COQ8B function

    Science.gov (United States)

    Vazquez Fonseca, Luis; Doimo, Mara; Calderan, Cristina; Desbats, Maria Andrea; Acosta, Manuel J.; Cerqua, Cristina; Cassina, Matteo; Ashraf, Shazia; Hildebrandt, Friedhelm; Sartori, Geppo; Navas, Placido; Trevisson, Eva

    2017-01-01

    Abstract Mutations in COQ8B cause steroid‐resistant nephrotic syndrome with variable neurological involvement. In yeast, COQ8 encodes a protein required for coenzyme Q (CoQ) biosynthesis, whose precise role is not clear. Humans harbor two paralog genes: COQ8A and COQ8B (previously termed ADCK3 and ADCK4). We have found that COQ8B is a mitochondrial matrix protein peripherally associated with the inner membrane. COQ8B can complement a ΔCOQ8 yeast strain when its mitochondrial targeting sequence (MTS) is replaced by a yeast MTS. This model was employed to validate COQ8B mutations, and to establish genotype–phenotype correlations. All mutations affected respiratory growth, but there was no correlation between mutation type and the severity of the phenotype. In fact, contrary to the case of COQ2, where residual CoQ biosynthesis correlates with clinical severity, patients harboring hypomorphic COQ8B alleles did not display a different phenotype compared with those with null mutations. These data also suggest that the system is redundant, and that other proteins (probably COQ8A) may partially compensate for the absence of COQ8B. Finally, a COQ8B polymorphism, present in 50% of the European population (NM_024876.3:c.521A > G, p.His174Arg), affects stability of the protein and could represent a risk factor for secondary CoQ deficiencies or for other complex traits. PMID:29194833

  1. CNS imaging findings associated with Parry-Romberg syndrome and en coup de sabre: correlation to dermatologic and neurologic abnormalities.

    Science.gov (United States)

    Doolittle, Derrick A; Lehman, Vance T; Schwartz, Kara M; Wong-Kisiel, Lily C; Lehman, Julia S; Tollefson, Megha M

    2015-01-01

    Parry-Romberg syndrome (PRS) and en coup de sabre (ECS) are variants of morphea. Although numerous findings on central nervous system (CNS) imaging of PRS and ECS have been reported, the spectrum and frequency of CNS imaging findings and relation to cutaneous and neurologic abnormalities have not been fully characterized. We retrospectively reviewed patients younger than 50 years at our institution over a 16-year interval who had clinical diagnosis of PRS and ECS by a skin or facial subspecialist. Two neuroradiologists evaluated available imaging and characterized CNS imaging findings. Eighty-eight patients with PRS or ECS were identified (62 women [70.4 %]; mean age 28.8 years). Of the 43 patients with CNS imaging, 19 (44 %) had abnormal findings. The only finding in 1 of these 19 patients was lateral ventricle asymmetry; of the other 18, findings were bilateral in 11 (61 %), ipsilateral to the side of facial involvement in 6 (33 %), and contralateral in 1 (6 %). Sixteen patients had serial imaging examinations over an average of 632 days; 13 (81 %) had stable imaging findings, and 3 (19 %) had change over time. Of six patients with progressive cutaneous findings, five (83 %) had stable imaging findings over time. Among the 23 patients with clinical neurologic abnormality and imaging, 12 (52 %) had abnormal imaging findings. All seven patients with seizures (100 %) had abnormal imaging studies. In PRS and ECS, imaging findings often are bilateral and often do not progress, regardless of cutaneous disease activity. Findings are inconsistently associated with clinical abnormalities.

  2. Urinary IgG and α2-Macroglobulin Are Powerful Predictors of Outcome and Responsiveness to Steroids and Cyclophosphamide in Idiopathic Focal Segmental Glomerulosclerosis with Nephrotic Syndrome

    Directory of Open Access Journals (Sweden)

    Claudio Bazzi

    2013-01-01

    Full Text Available Objective. To assess whether high-molecular-weight proteins excretion predicts outcome and therapy-responsiveness in patients with FSGS and nephrotic syndrome. Research Design and Methods. Thirty-eight patients measured at biopsy fractional excretion of IgG (FEIgG and urinary α2-macroglobulin/creatinine ratio (α2m/C. Low and high risk groups were defined by cutoffs assessed by ROC analysis. In all patients first-line therapy was with steroids alone or in combination with cyclophosphamide. Results. α2m/C and FEIgG were correlated with segmental sclerosis (r=0.546; r=0.522. Twenty-three patients (61% entered Remission and 9 (24% progressed to ESRD. Comparing low and high risk groups, by univariate analysis remission was predicted by FEIgG (77% versus 25%, P=0.016 and α2m/C (81% versus 17%, P=0.007 and ESRD at best by FEIgG (0% versus 75%, P<0.0001 and α2m/C (4% versus 67%, P<0.0001. By multivariate analysis FEIgG was the only independent predictor of remission and α2m/C the most powerful predictor of ESRD. Low and high risk groups of FEIgG and α2m/C in combination had very high predictive value of sustained remission and ESRD in response to therapy. Conclusions. FEIgG and α2m/C are powerful predictors of outcome and responsiveness to steroids and cyclophosphamide; their predictive value, if validated in prospective studies, may be useful in clinical practice suggesting first-line alternative treatments in high risk patients.

  3. Hipotiroidismo, miocardiopatía dilatada y síndrome nefrótico durante el embarazo Hypothyroidism, dilated cardiomyopathy and nephrotic syndrome during pregnancy

    Directory of Open Access Journals (Sweden)

    Ariel K. Saad

    2011-02-01

    Full Text Available El hipotiroidismo en el embarazo es infrecuente, pero cuando ocurre suele asociarse con complicaciones maternas y fetales. Se presenta el caso de una mujer joven sin antecedentes de enfermedad cardiovascular que consulta por ortopnea, dolor torácico y edema de miembros inferiores. Los exámenes pusieron en evidencia la existencia de insuficiencia cardíaca, hipotiroidismo, síndrome nefrótico e insuficiencia renal. El eco-Doppler mostró dilatación de las cuatro cavidades cardíacas con deterioro grave de la función sistólica. El tratamiento con levotiroxina por vía intravenosa mejoró el cuadro clínico y los parámetros de laboratorio. Se analizan los efectos de la hormona tiroidea sobre el aparato cardiovascular y se comentan los mecanismos fisiopatológicos de la insuficiencia cardíaca en el embarazo.Hypothyroidism during pregnancy is infrequent, but its presence is associated with maternal and fetal complications. We present the case of a young pregnant woman with no previous history of cardiovascular disease, who consulted for orthopnea, chest pain and edema in both legs. Laboratory tests demonstrated a hypothyroid condition and a nephrotic syndrome with renal failure. The echo-Doppler exam showed a four chamber dilatation with systolic dysfunction. Treatment with intravenous levothyroxine improved her medical condition. We analyze the effects of thyroid hormone on the heart and vascular system and discuss the pathophysiologic mechanisms of heart failure during pregnancy.

  4. Mutations in COQ8B (ADCK4) found in patients with steroid-resistant nephrotic syndrome alter COQ8B function.

    Science.gov (United States)

    Vazquez Fonseca, Luis; Doimo, Mara; Calderan, Cristina; Desbats, Maria Andrea; Acosta, Manuel J; Cerqua, Cristina; Cassina, Matteo; Ashraf, Shazia; Hildebrandt, Friedhelm; Sartori, Geppo; Navas, Placido; Trevisson, Eva; Salviati, Leonardo

    2018-03-01

    Mutations in COQ8B cause steroid-resistant nephrotic syndrome with variable neurological involvement. In yeast, COQ8 encodes a protein required for coenzyme Q (CoQ) biosynthesis, whose precise role is not clear. Humans harbor two paralog genes: COQ8A and COQ8B (previously termed ADCK3 and ADCK4). We have found that COQ8B is a mitochondrial matrix protein peripherally associated with the inner membrane. COQ8B can complement a ΔCOQ8 yeast strain when its mitochondrial targeting sequence (MTS) is replaced by a yeast MTS. This model was employed to validate COQ8B mutations, and to establish genotype-phenotype correlations. All mutations affected respiratory growth, but there was no correlation between mutation type and the severity of the phenotype. In fact, contrary to the case of COQ2, where residual CoQ biosynthesis correlates with clinical severity, patients harboring hypomorphic COQ8B alleles did not display a different phenotype compared with those with null mutations. These data also suggest that the system is redundant, and that other proteins (probably COQ8A) may partially compensate for the absence of COQ8B. Finally, a COQ8B polymorphism, present in 50% of the European population (NM_024876.3:c.521A > G, p.His174Arg), affects stability of the protein and could represent a risk factor for secondary CoQ deficiencies or for other complex traits. © 2017 The Authors. Human Mutation published by Wiley Periodicals, Inc.

  5. Serum lipid profile abnormalities among patients with nephrotic ...

    African Journals Online (AJOL)

    McRoy

    nephrotic syndrome. Adu E.M. Department of Laboratory Services, Antiretroviral Treatment Centre, Central Hospital, Agbor, Delta. State ... without any clinical and laboratory findings of renal dysfunction, hypertension or systemic ... was allowed to clot and spun in a centrifuge for. 10 minutes. The serum was separated and.

  6. Abdotninal cotnplications in black and Indian children with nephrotic ...

    African Journals Online (AJOL)

    nephrotic syndrome, are infection, hypovolaemia and thrombotic complications.I The survival rate of nephro- tic children was only 33% in the 1940s and it has been stated that penicillin has done more for the survival ... \\vith similar abdominal signs and symptoms; therefore the differentiation of peritonitis from hypovolaemia ...

  7. Acute glomerulonephritis mimicking nephrotic syndrome

    African Journals Online (AJOL)

    2016-01-04

    Jan 4, 2016 ... 0.3 cases per 100,000 person/ year.5 Thus, it is a disease of underdeveloped and ... The typical clinical presentation of PSGN which is a representative of a ... onset of microscopic haematuria, oedema, hypertension, oliguria ...

  8. Síndrome nefrótica córtico-sensível e diabetes mellitus tipo 1 de início simultâneo Simultaneous onset of steroid-sensitive nephrotic syndrome and type 1 diabetes

    Directory of Open Access Journals (Sweden)

    Eduardo A. Rego Filho

    2003-11-01

    with steroid-sensitive nephrotic syndrome coexisting with type-1 diabetes mellitus. The interest to this clinical case is due to the unusual association of these diseases, the clinical symptoms and laboratory tests used to confirm diagnosis and the difficulties on corticotherapy. DESCRIPTION: Nephrotic syndrome was diagnosed in a boy (age 3 years and 11 months with generalized edema. Marked weight loss (23 to 16 kg, polyuria, polydipsia and weakness were observed after three weeks of treatment with prednisone 2 mg/kg/day. Diabetic ketoacidosis was confirmed by laboratory tests: hyperglycemia (glucose 657 mg/dl, glycosuria without proteinuria, acidosis and ketonuria. Therapy with insulin and prednisone was started. He was then maintained on a daily dose of NPH insulin. At age 4 years and 1 month a new episode of ketoacidosis without proteinuria occurred in association with a viral infection of the upper airways. At age 4 years and 4 months nephrotic syndrome relapsed, but the child responded well to steroid therapy. There was another relapse three months later, when prednisone treatment was interrupted. This led to the introduction of cyclophosphamide, with good results. Since then, the patient (now 5 years and 6 months old has been taking insulin daily and nephrotic syndrome has not relapsed. Plasma levels of C3 and C4 and renal function are normal. Hematuria is occasionally present. Anti-GAD antibodies (glutamic decarboxilase are normal and anti-islet cell antibodies are positive. HLA antigens: A2; B44; B52; DR4; DR8; DR53. COMMENTS: The simultaneous occurrence of steroid-sensitive nephrotic syndrome and type-1 diabetes mellitus is rare. The literature data, the familiar pattern and studies on HLA antigens are discussed.

  9. Patterns in early diffusion-weighted MRI in children with haemolytic uraemic syndrome and CNS involvement

    International Nuclear Information System (INIS)

    Donnerstag, Frank; Ding, Xiaoqi; Bueltmann, Eva; Zajaczek, Jan; Lanfermann, Heinrich; Pape, Lars; Das, Anibh Martin; Ehrich, Jochen; Hartmann, Hans; Luecke, Thomas; Hoy, Ludwig

    2012-01-01

    Diffusion-weighted imaging (DWI) in children with diarrhoea associated haemolytic uraemic syndrome (D+HUS) and cerebral involvement was evaluated retrospectively. DWI within 24 h of onset of neurological symptoms. The apparent diffusion coefficient (ADC) was measured in grey/white matter and correlated with clinical and laboratory findings. DWI was abnormal in all. Abnormal ADC was detected in the supratentorial white matter (6/12) and cortex (1/12), the basal ganglia (5/12), the thalami (4/12), and the cerebellum (1/12). ADC was reduced in 5/12, increased in 4/12, and both in 3/12. Mean serum sodium was lower in patients with DWI abnormalities affecting the white matter (6/12), than in those with basal ganglia/thalamic involvement (6/12). Neurological outcome was normal in 4/11 and abnormal in 7/11, and 1 patient died, outcome did not correlate to either localisation or type of DWI abnormality. In D+HUS with neurological symptoms, early DWI may reveal abnormal ADC not only in the basal ganglia/thalami, but also in the white matter/cortex. Besides thrombotic microangiopathy, toxic effects of shiga toxin, azotaemia and hyponatraemia / hypoosmolality may be involved in cerebral involvement in children with D+HUS. Findings on early MRI seem not to predict clinical course or outcome. (orig.)

  10. Patterns in early diffusion-weighted MRI in children with haemolytic uraemic syndrome and CNS involvement

    Energy Technology Data Exchange (ETDEWEB)

    Donnerstag, Frank; Ding, Xiaoqi; Bueltmann, Eva; Zajaczek, Jan; Lanfermann, Heinrich [Hannover Medical School, Institute of Diagnostic and Therapeutic Neuroradiology, Hannover (Germany); Pape, Lars; Das, Anibh Martin; Ehrich, Jochen; Hartmann, Hans [Hannover Medical School, Clinic for Pediatric Kidney, Liver and Metabolic Diseases, Hannover (Germany); Luecke, Thomas [Hannover Medical School, Clinic for Pediatric Kidney, Liver and Metabolic Diseases, Hannover (Germany); University of Bochum, Department of Neuropediatrics, Pediatric Hospital, Bochum (Germany); Hoy, Ludwig [Hannover Medical School, Institute of Biometrics, Hannover (Germany)

    2012-03-15

    Diffusion-weighted imaging (DWI) in children with diarrhoea associated haemolytic uraemic syndrome (D+HUS) and cerebral involvement was evaluated retrospectively. DWI within 24 h of onset of neurological symptoms. The apparent diffusion coefficient (ADC) was measured in grey/white matter and correlated with clinical and laboratory findings. DWI was abnormal in all. Abnormal ADC was detected in the supratentorial white matter (6/12) and cortex (1/12), the basal ganglia (5/12), the thalami (4/12), and the cerebellum (1/12). ADC was reduced in 5/12, increased in 4/12, and both in 3/12. Mean serum sodium was lower in patients with DWI abnormalities affecting the white matter (6/12), than in those with basal ganglia/thalamic involvement (6/12). Neurological outcome was normal in 4/11 and abnormal in 7/11, and 1 patient died, outcome did not correlate to either localisation or type of DWI abnormality. In D+HUS with neurological symptoms, early DWI may reveal abnormal ADC not only in the basal ganglia/thalami, but also in the white matter/cortex. Besides thrombotic microangiopathy, toxic effects of shiga toxin, azotaemia and hyponatraemia / hypoosmolality may be involved in cerebral involvement in children with D+HUS. Findings on early MRI seem not to predict clinical course or outcome. (orig.)

  11. Differentiation of reversible ischemia from end-stage renal failure in nephrotic children with 131I-hippurate dynamic scintigraphy

    International Nuclear Information System (INIS)

    Hattner, R.S.; Maltz, H.E.; Holliday, M.A.

    1977-01-01

    In renal failure associated with the nephrotic syndrome, therapeutic strategy is highly dependent upon the cause of the renal failure. Dynamic hippurate scintigraphy was studied in five pediatric patients. Four had nephrotic syndrome, and of these, three had acute renal failure. The fifth patient had end-stage renal failure. Specific alteration in renal hippurate kinetics offers a noninvasive assessment of renal failure in this clinical setting

  12. Effect of two prophylactic bolus vitamin D dosing regimens (1000 IU/day vs. 400 IU/day) on bone mineral content in new-onset and infrequently-relapsing nephrotic syndrome: a randomised clinical trial.

    Science.gov (United States)

    Muske, Sravani; Krishnamurthy, Sriram; Kamalanathan, Sadish Kumar; Rajappa, Medha; Harichandrakumar, K T; Sivamurukan, Palanisamy

    2018-02-01

    To examine the efficacy of two vitamin D dosages (1000 vs. 400 IU/day) for osteoprotection in children with new-onset and infrequently-relapsing nephrotic syndrome (IFRNS) receiving corticosteroids. This parallel-group, open label, randomised clinical trial enrolled 92 children with new-onset nephrotic syndrome (NS) (n = 28) or IFRNS (n = 64) to receive 1000 IU/day (Group A, n = 46) or 400 IU/day (Group B, n = 46) vitamin D (administered as a single bolus initial supplemental dose) by block randomisation in a 1:1 allocation ratio. In Group A, vitamin D (cholecalciferol in a Calcirol® sachet) was administered in a single stat dose of 84,000 IU on Day 1 of steroid therapy (for new-onset NS), calculated for a period of 12 weeks@1000 IU/day) and 42,000 IU on Day 1 of steroid therapy (for IFRNS, calculated for a period of 6 weeks@1000 IU/day). In Group B, vitamin D (cholecalciferol in a Calcirol® sachet) was administered as a single stat dose of 33,600 IU on Day 1 of steroid therapy (for new-onset NS, calculated for a period of 12 weeks@400 IU/day) and 16,800 IU on Day 1 of steroid therapy (for IFRNS, calculated for a period of 6 weeks@400 IU/day). The proportionate change in bone mineral content (BMC) was analysed in both groups after vitamin D supplementation. Of the 92 children enrolled, 84 (n = 42 new onset, n = 42 IFRNS) completed the study and were included in the final analysis. Baseline characteristics including initial BMC, bone mineral density, cumulative prednisolone dosage and serum 25-hydroxycholecalciferol levels were comparable in the two groups. There was a greater median proportionate change in BMC in the children who received 1000 IU/day vitamin D (3.25%, IQR -1.2 to 12.4) than in those who received 400 IU/day vitamin D (1.2%, IQR -2.5 to 3.8, p = 0.048). The difference in proportionate change in BMC was only statistically significant in the combined new-onset and IFRNS, but not for IFRNS alone. There was a greater

  13. CNS involvement in primary Sjogren Syndrome: assessment of gray and white matter changes with MRI and voxel-based morphometry.

    Science.gov (United States)

    Tzarouchi, Loukia C; Tsifetaki, Niki; Konitsiotis, Spyridon; Zikou, Anastasia; Astrakas, Loukas; Drosos, Alexandros; Argyropoulou, Maria I

    2011-11-01

    The purpose of this study was to evaluate with MRI the involvement of gray matter and white matter structures in patients with primary Sjögren syndrome. Fifty-three patients with primary Sjögren syndrome, 18 age- and disease duration-matched patients with systemic sclerosis, and 35 age-matched control subjects were examined for differences in white matter hyperintensities (WMHIs) detected on FLAIR MR images. Differences in brain volume between patients with primary Sjögren syndrome and controls were studied by application of voxel-based morphometry to a 3D T1-weighted sequence. WMHIs were observed in 38 of the 53 patients with primary Sjögren syndrome, six of 18 patients with systemic sclerosis, and 17 of 35 controls. The numbers of WMHIs 2 mm or larger and the number smaller than 2 mm were higher in patients with primary Sjögren syndrome than in controls (≥ 2 mm, p = 0.004; syndrome patients and that in systemic sclerosis patients. After control for age, a positive relation was found between disease duration and total number of WMHIs (p = 0.037) and number of WMHIs 2 mm or larger (p = 0.023) in patients with primary Sjögren syndrome. In comparison with the controls, patients with primary Sjögren syndrome had decreased gray matter volume in the cortex, deep gray matter, and cerebellum. Associated loss of white matter volume was observed in areas corresponding to gray matter atrophy and in the corpus callosum (p syndrome have WMHIs and gray and white matter atrophy, probably related to cerebral vasculitis.

  14. Supratentorial CNS malformations

    International Nuclear Information System (INIS)

    Zlatareva, D.

    2012-01-01

    Full text: Clinical suspicion of a developmental anomaly of the central nervous system (CNS) is a frequent indication for performing and magnetic resonance imaging (MRI) examination of the brain. Classification systems for malformation of the CNS are constantly revised according to newer scientific research. Developmental abnormalities can be classified in two main types. The first category consists of disorders of organogenesis in which genetic defects or any ischemic, metabolic, toxic or infectious insult to the developing brain can cause malformation. These malformations result from abnormal neuronal and glial proliferation and from anomalies of neuronal migration and or cortical organization. They are divided into supra- and infratentorial and may involve grey or white matter or both. The second category of congenital brain abnormalities is disorders of histogenesis which result from abnormal cell differentiation with a relatively normal brain appearance. Supratentorial CNS malformations could be divided into anomalies in telencephalic commissure, holoprosencephalies and malformations in cortical development. There are three main telencephalic commissures: the anterior commissure, the hippocampal commissure and the corpus callosum. Their morphology (hypoplasia, hyperplasia, agenesis, dysgenesis, even atrophy) reflects the development of the brain. Their agenesis, complete or partial, is one of the most commonly observed features in the malformations of the brain and is a part of many syndromes. Malformations of cortical development (MCD) are heterogeneous group of disease which result from disruption of 3 main stages of cortical development. The common clinical presentation is refractory epilepsy and or developmental delay. The most common MCD are heterotopias, focal cortical dysplasia, polymicrogyria, schizencephaly, pachygyria and lizencephaly. The exact knowledge of the brain anatomy and embryology is mandatory to provide a better apprehension of the

  15. APOL1-associated glomerular disease among African-American children: a collaboration of the Chronic Kidney Disease in Children (CKiD) and Nephrotic Syndrome Study Network (NEPTUNE) cohorts.

    Science.gov (United States)

    Ng, Derek K; Robertson, Catherine C; Woroniecki, Robert P; Limou, Sophie; Gillies, Christopher E; Reidy, Kimberly J; Winkler, Cheryl A; Hingorani, Sangeeta; Gibson, Keisha L; Hjorten, Rebecca; Sethna, Christine B; Kopp, Jeffrey B; Moxey-Mims, Marva; Furth, Susan L; Warady, Bradley A; Kretzler, Matthias; Sedor, John R; Kaskel, Frederick J; Sampson, Matthew G

    2017-06-01

    Individuals of African ancestry harboring two variant alleles within apolipoprotein L1 ( APOL1 ) are classified with a high-risk (HR) genotype. Adults with an HR genotype have increased risk of focal segmental glomerulosclerosis and chronic kidney disease compared with those with a low-risk (LR) genotype (0 or 1 variants). The role of APOL1 risk genotypes in children with glomerular disease is less well known. This study characterized 104 African-American children with a glomerular disease by APOL1 genotype in two cohorts: the Chronic Kidney Disease in Children (CKiD) and Nephrotic Syndrome Study Network (NEPTUNE). Among these subjects, 46% had an HR genotype with a similar age at cohort enrollment. For APOL1 HR children, the median age of disease onset was older (CKiD: 4.5 versus 11.5 years for LR versus HR; NEPTUNE: 11 versus 14 years for LR versus HR, respectively) and preterm birth was more common [CKiD: 27 versus 4%; NEPTUNE: 26 versus 12%; combined odds ratio 4.6 (95% confidence interval: 1.4, 15.5)]. Within studies, HR children had lower initial estimated glomerular filtration rate (eGFR) (CKiD: 53 versus 69 mL/min/1.73 m 2 ; NEPTUNE: 74 versus 94 mL/min/1.73 m 2 ). Longitudinal eGFR decline was faster among HR children versus LR (CKiD: -18 versus -8% per year; NEPTUNE: -13 versus -3% per year). Children with an HR genotype in CKiD and NEPTUNE seem to have a more aggressive form of glomerular disease, in part due to a higher prevalence of focal segmental glomerulosclerosis. These consistent findings across independent cohorts suggest a common natural history for children with APOL1 -associated glomerular disease. Further study is needed to determine the generalizability of these findings. © The Author 2016. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  16. fMRI Reveals Distinct CNS Processing during Symptomatic and Recovered Complex Regional Pain Syndrome in Children

    Science.gov (United States)

    Lebel, A.; Becerra, L.; Wallin, D.; Moulton, E. A.; Morris, S.; Pendse, G.; Jasciewicz, J.; Stein, M.; Aiello-Lammens, M.; Grant, E.; Berde, C.; Borsook, D.

    2008-01-01

    Complex regional pain syndrome (CRPS) in paediatric patients is clinically distinct from the adult condition in which there is often complete resolution of its signs and symptoms within several months to a few years. The ability to compare the symptomatic and asymptomatic condition in the same individuals makes this population interesting for the…

  17. Reduced activity of 11beta-hydroxysteroid dehydrogenase type 2 is not responsible for sodium retention in nephrotic rats

    DEFF Research Database (Denmark)

    Bistrup, C; Thiesson, H C; Jensen, B L

    2005-01-01

    AIM: In mineralocorticoid target cells 11-beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) converts glucocorticoids into non-active metabolites thereby protecting the mineralocorticoid receptor (MR) from stimulation by glucocorticoids. In nephrotic syndrome, a decreased activity of 11betaHSD2...... has been suggested to allow glucocorticoids to stimulate MR, thereby contributing to sodium retention. We tested this hypothesis in the puromycin aminonucleoside model of nephrotic syndrome in rats. METHODS: Complete sodium and potassium intakes and excretions (faeces and urine) were measured in rats......)] to suppress endogenous glucocorticoids in the proteinuric stage during active sodium retention. RESULTS: Nephrotic rats developed proteinuria, positive sodium balance, decreased plasma aldosterone concentration, and decreased urinary Na(+)/K(+) ratio. 11betaHSD2 mRNA expression was down-regulated but protein...

  18. The intellectual capacity of patients with Laron syndrome (LS) differs with various molecular defects of the growth hormone receptor gene. Correlation with CNS abnormalities.

    Science.gov (United States)

    Shevah, O; Kornreich, L; Galatzer, A; Laron, Z

    2005-12-01

    The correlation between the molecular defects of the GH receptor (R), psychosocial development and brain abnormalities were evaluated in 10 patients with Laron syndrome (LS), in whom all data were available. The findings revealed that the intelligence quotient (IQ) and abnormalities in the brain of the patients with LS differ with various molecular defects of the GH-receptor. The most severe mental deficits and brain pathology occurred in patients with 3, 5, 6 exon deletion. Patients with point mutations in exons 2, 4 and 7 presented various degrees of medium to mild CNS abnormalities that correlated with the IQ. Notably, the patient with the E180 splice mutation in exon 6 had a normal IQ, which fits the report on normal IQ in a large Ecuadorian cohort with the same mutation. This is the first report to support a correlation between IQ, brain abnormalities and localization of the molecular defects in the GH-R gene. As all patients with LS are IGF-I-deficient, it must be assumed that other as yet unknown factors related to the molecular defects in the GH-R are the major cause of the differences in intellect and brain abnormalities.

  19. Idiopathic nephrotic syndrome in South African children.

    African Journals Online (AJOL)

    The majority (68.1%) of the 163 children were of the black racial group. The highest ... segmental glomerulosclerosis (FSGS), and the white race had the highest rate (9/14; 64.3%) of minimal change disease (MCD). ..... reported from India (11.4%), Turkey (17%) and the US. (25%) ... The authors declare no conflict of interest.

  20. Congenital nephrotic syndrome: A diagnostic and management ...

    African Journals Online (AJOL)

    viz. syphilis, hepatitis B and C and rubella were negative. Due to lack of resources ... (personal communication, Adhikari). It is, however, possible that .... Benfield MR, McDonald RA, Bartosh S, Ho PL, Harmon W. Changing trends in pediatric ...

  1. Cyclosporin in steroid- resistant nephrotic syndrome

    African Journals Online (AJOL)

    1994-11-11

    Nov 11, 1994 ... steroid-unresponsive and alternative therapies therefore need to be assessed. ..... glomerular sclerosis. No vascular or tubular epithelial lesions ... acute tubular necrosis, and probable cyclosporin toxicity. No renal biopsy ...

  2. Glucocorticoid-induced osteoporosis in the lumbar spine, forearm, and mandible of nephrotic patients

    DEFF Research Database (Denmark)

    Olgaard, K; Storm, Tina; van Wowern, N

    1992-01-01

    /day and tapered down to 20 mg/day for 1 year and DFZ was given in an equipotent dosage. Twenty-three patients completed 6 months of treatment, and 18 patients completed 12 months of treatment. Beside laboratory parameters to ensure the effect of treatment on the nephrotic syndrome, all had measurements......The long-term effects of high dose steroid treatment with either prednisone (PDN) or deflazacort (DFZ) were examined on various parts of the skeleton in 29 patients with nephrotic syndrome. All had normal skeleton at the start of the steroid treatment. At the beginning, PDN was given as 80 mg...... of the bone mineral content (BMC) at 0, 6, and 12 months of treatment. BMC was measured by single photon absorptiometry of both forearms and by dual photon absorptiometry of the mandible, forearms, and lumbar spine. The effect of DFZ was compared to that of PDN due to a potential "calcium sparing" effect...

  3. Serum erythropoietin level in anemic and non-anemic nephrotic children with normal kidney functions

    International Nuclear Information System (INIS)

    Moustafa, A.M.E.; Moawad, A.T.; Gad, A.A.; Ahmed, S.M.

    2005-01-01

    Nephrotic syndrome (NS) is associated with a significant alteration in protein metabolism. While lowering the concentration of certain proteins, the disease often raises the level of certain other proteins. The current study aimed to investigate the serum erythropoietin (EPO) levels in children with NS either anemic or non-anemic and to compare them to children with iron deficiency anemia (IDA) and healthy controls with normal hemoglobin level (NHB). Sixteen nephrotic children with anemia (NS-A) and 15 nephrotic children with normal hemoglobin level (NS-NHB) were examined and compared with 10 children with iron deficiency anemia (IDA) and 10 healthy controls (NHB). Circulating serum EPO levels, blood indices and iron status were measured in nephrotic patients with anemia (NS-A) and compared to those nephrotic patients with normal HE (NS-NHB). Most NS-A children were steroid resistant. The NS-A children showed greater EPO levels than those without anemia (21.01 ±4.02 mlU/ml versus 9.18 ± 0.79 mlU/ml; P < 0.001) but their response to treatment of anemia was inappropriately low when compared to IDA (EPO 96.9 ±4.9 mlU/ml) despite similar HB concentration. A significant positive correlation was observed between serum EPO and serum albumin in NS-A (r = 0.84, P < 0.001) and in NS-NHB group (r = 0.89, P < 0.001). Moreover, a significant positive correlation was observed between serum EPO and HB in the nephrotic groups indicating a blunted EPO response to anemia in NS-A (r 0.63, P < 0.05) and in NS-NHB group (r = 0.80, P < 0.001). In conclusion, anemia is a common feature of NS and is present even before the worsening of kidney function. Depletion of the iron stores due to loss of iron and transferrin in urine due to massive proteinurea may contribute to the development of anemia, but it was found that iron replacement was ineffective alone

  4. CNS role evolution.

    Science.gov (United States)

    Payne, J L; Baumgartner, R G

    1996-01-01

    THE CNS ROLE has been actualized in a variety of ways. Flexibility-inherent in the role-and the revolution in health care consciousness tend to place the CNS at risk for criticism regarding value to the organization. At Vanderbilt University Medical Center, a CNS task force evaluated the current reality of CNS practice and recommended role changes to include the financial analysis of patient care. After incorporating a financial perspective into our present practice, we have embarked on an interesting journey of post-Master's degree study, that of the tertiary care nurse practitioner. This practice option could elevated the clinical and financial aspects of providing cost-effective health care to a more autonomous role form; however, the transition has been challenging. Since 1990, the American Nurses Association has recommended that nursing school curricula change to meet the needs of the health care environment and provide increased career flexibility through creating one advanced degree incorporating both CNS and NP functions. Swiftly moving past differences and toward similarities will bridge the gap for advanced practice nurses in the future.

  5. Are oxidized low-density lipoprotein and C-reactive protein markers of atherosclerosis in nephrotic children?

    OpenAIRE

    Rybi-Szumińska, A.; Wasilewska, A.; Michaluk-Skutnik, J.; Osipiuk-Remża, B.; Fiłonowicz, R.; Zając, M.

    2014-01-01

    Background Lipid disorders are known to be linked to disturbance in oxidative reactions and play an important role in the progression and complications of idiopathic nephrotic syndrome (INS). Aims The aim of this study was to assess oxidized low-density lipoprotein (oxLDL), high-sensitive C-reactive protein (hs-CRP) serum concentrations and other parameters of lipid metabolism in children with INS during relapse and remission of proteinuria. Methods The examination was performed on 23 childre...

  6. VIIP: Central Nervous System (CNS) Modeling

    Science.gov (United States)

    Vera, Jerry; Mulugeta, Lealem; Nelson, Emily; Raykin, Julia; Feola, Andrew; Gleason, Rudy; Samuels, Brian; Ethier, C. Ross; Myers, Jerry

    2015-01-01

    Current long-duration missions to the International Space Station and future exploration-class missions beyond low-Earth orbit expose astronauts to increased risk of Visual Impairment and Intracranial Pressure (VIIP) syndrome. It has been hypothesized that the headward shift of cerebrospinal fluid (CSF) and blood in microgravity may cause significant elevation of intracranial pressure (ICP), which in turn may then induce VIIP syndrome through interaction with various biomechanical pathways. However, there is insufficient evidence to confirm this hypothesis. In this light, we are developing lumped-parameter models of fluid transport in the central nervous system (CNS) as a means to simulate the influence of microgravity on ICP. The CNS models will also be used in concert with the lumped parameter and finite element models of the eye described in the related IWS works submitted by Nelson et al., Feola et al. and Ethier et al.

  7. Immunosuppressive treatment for nephrotic idiopathic membranous nephropathy: a meta-analysis based on Chinese adults.

    Directory of Open Access Journals (Sweden)

    Guoqiang Xie

    Full Text Available Idiopathic membranous nephropathy (IMN is the most common pathological type for nephrotic syndrome in adults in western countries and China. The benefits and harms of immunosuppressive treatment in IMN remain controversial.To assess the efficacy and safety of different immunosuppressive agents in the treatment of nephrotic syndrome caused by IMN.PubMed, EMBASE, Cochrane Library and wanfang, weipu, qinghuatongfang, were searched for relevant studies published before December 2011. Reference lists of nephrology textbooks, review articles were checked. A meta-analysis of randomized controlled trials (RCTs meeting the criteria was performed using Review Manager.17 studies were included, involving 696 patients. Calcineurin inhibitors had a better effect when compared to alkylating agents, on complete remission (RR 1.61, 95% CI 1.13, to 2.30 P = 0.008, partial or complete remission (effective (CR/PR, RR 1.29, 95% CI 1.09 to 1.52 P = 0.003, and fewer side effects. Among calcineurin inhibitors, tacrolimus (TAC was shown statistical significance in inducing more remissions. When compared to cyclophosphamide (CTX, leflunomide (LET showed no beneficial effect, mycophenolate mofetil (MMF showed significant beneficial on effectiveness (CR/PR, RR: 1.41, 95% CI 1.16 to 1.72 P = 0.0006 but not significant on complete remission (CR, RR: 1.38, 95% CI 0.89 to 2.13 P = 0.15.This analysis based on Chinese adults and short duration RCTs suggested calcineurin inhibitors, especially TAC, were more effective in proteinuria reduction in IMN with acceptable side effects. Long duration RCTs were needed to confirm the long-term effects of those agents in nephrotic IMN.

  8. Padrões morfológicos de lesão glomerular e correlação com achados clinicolaboratoriais de 43 crianças com síndrome nefrótica Morphologic patterns of glomerular lesion and correlation with clinical and laboratory findings of 43 children with nephrotic syndrome

    Directory of Open Access Journals (Sweden)

    Márcia Camegaçava Riyuzo

    2004-10-01

    Full Text Available OBJETIVOS: Avaliar a associação entre os parâmetros clinicolaboratoriais e alteração morfológica de biópsias renais em crianças com síndrome nefrótica. MÉTODOS: Os dados foram obtidos dos prontuários médicos de 43 crianças com síndrome nefrótica submetidas a biópsia renal. RESULTADOS: Vinte e oito pacientes eram do sexo masculino (65,1%, idades entre 1,4 a 12 anos (média de 4,7±3,2. Quarenta e dois pacientes (97,7% apresentaram edema; 83,7%, oligúria e 32,5%, hipertensão arterial. A média de proteinúria foi 15,3g/1,73m²SC/dia e 55,8% apresentaram hematúria microscópica. As biópsias renais mostraram: glomerulonefrite proliferativa mesangial (GNPM em 37,2%, glomeruloesclerose segmentar e focal (GESF em 27,9%, alterações glomerulares mínimas (LM em 25,6%, glomerulonefrite membranoproliferativa (GNMP em 7% e glomerulonefrite membranosa (GNM em 2,3%. Vinte e seis pacientes (60,5% apresentaram resistência ao corticosteróide. Idade, sexo, hipertensão arterial, oligúria, uréia e creatinina séricas não mostraram diferenças estatísticas significativas entre os pacientes com GNPM, GESF e LM. Os pacientes com GNPM e GESF apresentaram maior freqüência de hematúria microscópica (p OBJECTIVES: To evaluate the association between clinical features and laboratory findings with the morphological changes in children with nephrotic syndrome. METHODS: The data were obtained from medical records of 43 children with nephrotic syndrome submitted to renal biopsy. RESULTS: Twenty-eight patients were male (65.1%, aged 1.4-12 years (mean 4.7 ± 3,2. Forty-two patients (97,7% presented edema, 83.7% oliguria and 32.5% hypertension. The mean of proteinuria was 15.3g/1.73m² BSA per day and 55.8% presented microscopic hematuria. Renal biopsies showed: proliferative mesangial glomerulonephritis (PMGN in 37.2%, focal segmental glomerulosclerosis (FSGS in 27.9%, minimal change disease (MCD in 25.6%, membranoproliferative

  9. Frequency and clinicopathological correlations of histopathological variants of idiopathic focal segmental glomerulosclerosis in nephrotic adolescents

    International Nuclear Information System (INIS)

    Shakeel, S.; Mubarak, M.; Kazi, J.I.

    2014-01-01

    Objective: To determine the frequency and clinicopathological correlations of focal segmental glomerulosclerosis variants in adolescents with idiopathic nephrotic syndrome. Methods: All consecutive adolescents (12 to 18 years) who presented with idiopathic nephrotic syndrome in the period, January 2009 to December 2012, and in whom the histological diagnosis of focal segmental glomerulosclerosis was made on renal biopsies, were included in this prospective study. Their clinical, laboratory and histopathological features at the time of presentation or biopsy were noted from the case files and the biopsy reports. Results: Among 50 adolescents, 34 (68%) were males and 16 (32%) females. The mean age was 15.14+-2.3 years. The mean duration of disease was 6.3+-11.2 months. The mean serum creatinine was 0.96+-0.82 mg/dl. The mean 24-hour urinary protein excretion was 3.8+-0.68 grams. Biopsy indications were steroid-resistant nephritic syndrome in 15 (30%), steroid-dependant nephritic syndrome in 19 (38%) and adolescent nephritic syndrome in 16 (32%) cases. Among the focal segmental glomerulosclerosis variants, 40 (80%) were not otherwise specified, followed by the collapsing variant, which accounted for 8 (16%) cases. The tip and cellular variants, both were found in one (2%) case each. Among the histological features, global glomerulosclerosis was found in 23 (46%) cases, and segmental scarring/collapse in all (100%). A variable degree of tubular atrophy and interstitial fibrosis was noted in 44 (88%) cases. Conclusion: The results from this study indicate that the pattern of focal segmental glomerulosclerosis variants differs markedly in adolescents compared with younger children. (author)

  10. Management of CNS tumors

    International Nuclear Information System (INIS)

    Griem, M.L.

    1987-01-01

    The treatment of tumors of the CNS has undergone a number of changes based on the impact of CT. The use of intraoperative US for the establishment of tumor location and tumor histology is demonstrated. MR imaging also is beginning to make an impact on the diagnosis and treatment of tumors of the CNS. Examples of MR images are shown. The authors then discuss the important aspects of tumor histology as it affects management and newer concepts in surgery, radiation, and chemotherapy on tumor treatment. The role of intraoperative placement of radioactive sources, the utilization of heavy particle radiation therapy, and the potential role of other experimental radiation therapy techniques are discussed. The role of hyperfractionated radiation and of neutrons and x-ray in a mixed-beam treatment are discussed in perspective with standard radiation therapy. Current chemotherapy techniques, including intraarterial chemotherapy, are discussed. The complications of radiation therapy alone and in combination with chemotherapy in the management of primary brain tumors, brain metastases, and leukemia are reviewed. A summary of the current management of pituitary tumors, including secreting pituitary adenomas and chromophobe adenomas, are discussed. The treatment with heavy particle radiation, transsphenoidal microsurgical removal, and combined radiotherapeutic and surgical management are considered. Tumor metastasis management of lesions of the brain and spinal cord are considered

  11. CNS effects following the treatment of malignancy

    International Nuclear Information System (INIS)

    Rane, N.; Quaghebeur, G.

    2012-01-01

    Corporeal and central nervous system (CNS) axis chemotherapy and radiotherapy have long been used for the effective treatment and prophylaxis of CNS, body malignancies, and leukaemias. However, they are not without their problems. Following the proliferation of magnetic resonance neuroimaging in recent years it has become clear that the spectrum of toxicity that these therapies produce ranges from subclinical white matter changes to overt brain necrosis. The effects are both direct and indirect and via different pathological mechanisms. Chronic and progressive changes can be detected many years after the initial intervention. In addition to leucoencephalopathic changes, grey matter changes are now well described. Changes may be difficult to distinguish from tumour recurrence, though may be reversible and remediable, and are thus very important to differentiate. In this review toxic effects are classified and their imaging appearances discussed, with reference to specific syndromes.

  12. Cerebral blood flow variations in CNS lupus

    International Nuclear Information System (INIS)

    Kushner, M.J.; Tobin, M.; Fazekas, F.; Chawluk, J.; Jamieson, D.; Freundlich, B.; Grenell, S.; Freemen, L.; Reivich, M.

    1990-01-01

    We studied the patterns of cerebral blood flow (CBF), over time, in patients with systemic lupus erythematosus and varying neurologic manifestations including headache, stroke, psychosis, and encephalopathy. For 20 paired xenon-133 CBF measurements, CBF was normal during CNS remissions, regardless of the symptoms. CBF was significantly depressed during CNS exacerbations. The magnitude of change in CBF varied with the neurologic syndrome. CBF was least affected in patients with nonspecific symptoms such as headache or malaise, whereas patients with encephalopathy or psychosis exhibited the greatest reductions in CBF. In 1 patient with affective psychosis, without clinical or CT evidence of cerebral ischemia, serial SPECT studies showed resolution of multifocal cerebral perfusion defects which paralleled clinical recovery

  13. Flavonoids and the CNS

    DEFF Research Database (Denmark)

    Jäger, Anna Katharina; Saaby, Lasse

    2011-01-01

    Flavonoids are present in almost all terrestrial plants, where they provide UV-protection and colour. Flavonoids have a fused ring system consisting of an aromatic ring and a benzopyran ring with a phenyl substituent. The flavonoids can be divided into several classes depending on their structure....... Flavonoids are present in food and medicinal plants and are thus consumed by humans. They are found in plants as glycosides. Before oral absorption, flavonoids undergo deglycosylation either by lactase phloridzin hydrolase or cytosolic ß-glucocidase. The absorbed aglycone is then conjugated by methylation......, sulphatation or glucuronidation. Both the aglycones and the conjugates can pass the blood-brain barrier. In the CNS several flavones bind to the benzodiazepine site on the GABA(A)-receptor resulting in sedation, anxiolytic or anti-convulsive effects. Flavonoids of several classes are inhibitors of monoamine...

  14. INHERITED PATHOLOGY OF β2-LAMININ (PIERSON SYNDROME: CLINICAL AND GENETIC ASPECTS

    Directory of Open Access Journals (Sweden)

    M.Yu. Kagan

    2010-01-01

    Full Text Available For the last decade a great successes were attained in the study of molecular bases of glomerular diseases. It was certain that the most frequent reasons of congenital and infantile nephrotic syndrome are mutations in the genes of NPHS1, NPHS2, and WT1. Nevertheless, until now, a number of patients, having combination of early nephrotic syndrome with inherent pathology of other organs, which etiology remains un known. These cases continue to be intensively probed. One of the most important recent achievements in understanding of molecular mechanisms of early nephrotic syndrome is the discovery of mutations of gene of LAMB2, encoding β2 laminin, as the cause of Pearson syndrome (OMIM#609049. In this article the author presents the basic genetic and clinical descriptions of this recently identified pathology. Key words: Pearson syndrome, congenital nephrotic syndrome, β2 laminin, malformation of organ of vision. (Pediatric Pharmacology. – 2010; 7(3:114-117

  15. Isolated vasculitis of the CNS

    International Nuclear Information System (INIS)

    Block, F.; Reith, W.

    2000-01-01

    Vasculitis is a rare cause for disease of the CNS. The isolated vasculitis of the CNS is restricted to the CNS whereas other forms of vasculitis affect various organs including the CNS. Headache, encephalopathy, focal deficits and epileptic seizures are the major symptoms suggestive for vasculitis. One major criterion of the isolated vasculitis of the CNS is the lack of evidence for other vasculitis forms or for pathology of other organs. Angiography displays multifocal segmental stenosis of intracranial vessels. MRI demonstrates multiple lesions which in part show enhancement after gadolinium. A definite diagnosis can only be made on the grounds of biopsy from leptomeninges and parenchyma. Therapy consists of corticosteroids and cyclophosphamid. (orig.) [de

  16. Flavonoids and the CNS

    Directory of Open Access Journals (Sweden)

    Anna K. Jäger

    2011-02-01

    Full Text Available Flavonoids are present in almost all terrestrial plants, where they provide UV-protection and colour. Flavonoids have a fused ring system consisting of an aromatic ring and a benzopyran ring with a phenyl substituent. The flavonoids can be divided into several classes depending on their structure. Flavonoids are present in food and medicinal plants and are thus consumed by humans. They are found in plants as glycosides. Before oral absorption, flavonoids undergo deglycosylation either by lactase phloridzin hydrolase or cytosolic β-glucocidase. The absorbed aglycone is then conjugated by methylation, sulphatation or glucuronidation. Both the aglycones and the conjugates can pass the blood-brain barrier. In the CNS several flavones bind to the benzodiazepine site on the GABAA-receptor resulting in sedation, anxiolytic or anti-convulsive effects. Flavonoids of several classes are inhibitors of monoamine oxidase A or B, thereby working as anti-depressants or to improve the conditions of Parkinson’s patients. Flavanols, flavanones and anthocyanidins have protective effects preventing inflammatory processes leading to nerve injury. Flavonoids seem capable of influencing health and mood.

  17. Tolvaptan alleviates excessive fluid retention of nephrotic diabetic renal failure unresponsive to furosemide.

    Science.gov (United States)

    Takada, Tesshu; Masaki, Tsuguto; Hoshiyama, Ayako; Toki, Takuya; Kamata, Yuji; Shichiri, Masayoshi

    2018-04-17

    Patients with diabetic nephropathy develop nephrotic syndrome, and may show limited response to conventional therapy. They often require earlier initiation of renal replacement therapy because they become refractory to diuretics, and experience excessive fluid retention. We aimed to investigate the efficacy of tolvaptan, an oral arginine vasopressin type 2 receptor antagonist, in a case series of 14 severe diabetic renal failure patients who were severely refractory to maximal doses of furosemide and had excessive fluid retention despite preserved cardiac function and residual renal function. All 14 patients experienced immediate and sustained water diuretic effects, resulting in alleviation of congestive heart failure. None required initiation of renal replacement therapy. Tolvaptan promptly increased urine volume and free water clearance, reversed progressive fluid retention, and alleviated congestive heart failure. Thus, tolvaptan could serve as a potential adjunct therapy for severe diabetic renal failure patients with excessive fluid retention and congestive heart failure. This article is protected by copyright. All rights reserved.

  18. CNS infections in immunocompetent patients

    International Nuclear Information System (INIS)

    Hartmann, K.M.; Zimmer, A.; Reith, W.

    2008-01-01

    This article gives a review of the most frequent infective agents reasonable for CNS infections in immunocompetent patients as well as their localisation and imaging specifications. MRI scanning is the gold standard to detect inflammatory conditions in the CNS. Imaging can be normal or nonspecifically altered although the infection is culturally or bioptically proven. There are no pathognomonic, pathogen-specific imaging criteria. The localization and dimension of the inflammation depends on the infection pathway. (orig.) [de

  19. Application of empowerment theory for CNS practice.

    Science.gov (United States)

    Carlson-Catalano, J M

    1993-11-01

    Power is necessary for the clinical nurse specialist (CNS) to successfully conduct objectives of practice in bureaucratic hospital settings. To obtain power, the CNS could use strategies of an empowerment theory to fully operationalize roles in hospitals. This article will discuss how the CNS may be empowered utilizing strategies in four empowering categories. In addition, the many benefits of empowering the CNS are reviewed.

  20. Case study of a patient with severe nephrotic syndrome.

    Science.gov (United States)

    de Guzman, L; Joyce, K

    1991-10-01

    M.T. battled SLE for 9 years before renal failure occurred. She is now free of extrarenal symptoms of lupus, as has been described elsewhere (Ziff & Hilderman, 1983). The patient has regained here appetite, lost 13 pounds, recovered some strength and reestablished her social network. Without the severe proteinuria, M.T. has a chance to improve her nutritional status and increase her albumin. Her pulmonary status may also improve if she can refrain from smoking. Although fatigue is a debilitating feature of lupus, M.T. has increased stamina and is learning energy conservation techniques. Immediately after surgery, she did experience problems with bleeding, pneumonia, and pleural effusions, but the medical and nursing management prevented serious adverse outcomes. Fluid balance is no longer problematic, and M.T. is approaching her ideal body weight as her nutritional status improves. Her serum albumin has increased to about 2.6 gm/dl with some decrease in her proteinuria.

  1. Circulating dendritic cells in pediatric patients with nephrotic syndrome

    African Journals Online (AJOL)

    Background: Dendritic cells (DCs) represent one of the most extensively studied topics in immunology, because of their central role in the induction and regulation of adaptive immunity, and because of their therapeutic potential for manipulating immune responses. Objectives: To evaluate circulating DC levels in pediatric ...

  2. Acute radiation sickness - morphology of CNS syndrome

    International Nuclear Information System (INIS)

    Kamarad, V.

    1989-01-01

    The effect was studied of supralethal doses of 60 Co gamma radiation on morphological changes in the brains of laboratory animals. For experiments, female rats irradiated with doses of 15 to 960 Gy, female mice irradiated with doses of 50 to 300 Gy and dogs irradiated with 6 to 500 Gy were used. For evaluation of the changes, light microscopy, electron microscopy and histochemistry were employed. The findings generally agreed with the results by other authors whose numerous studies are reviewed in detail. They included brain edema, alterations in enzyme activities, dystrophic changes and hemorrhages in nerve cells, marked structural changes in blood capillaries, damage of endothelial cells, etc. The observed changes in the activities of blood-brain barrier enzymes, increased pinocytotic activity and the formation of endothelial tunnels accompanied with necrosis of part of endothelial cells are clear morphological manifestations of marked alterations in the function of the blood-brain barrier that result in brain edema development. The increased permeability of the blood-brain barrier significantly worsens primary changes induced by radiation, especially in nerve cels, and adversely affects possible repair processes. (L.O.). 146 figs., 8 tabs., 352 refs

  3. Innate Interferons Regulate CNS Inflammation

    DEFF Research Database (Denmark)

    Dieu, Ruthe; Khorooshi, Reza M. H.; Mariboe, Anne

    Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) whose pathology is characterised by demyelination and axonal damage. This results from interplay between CNS-resident glia, infiltrating leukocytes and a plethora of cytokines and chemokines. Currently...... potential IFN-inducing receptor that signals through NF-kB. Receptor activator of NF-kB (RANK) belongs to the TNF-receptor superfamily and has been shown to induce IFN-beta in medullary thymic epithelial cells affecting autoimmune regulatory processes and osteoclast precursor cells in association to bone...

  4. Genetic models for CNS inflammation

    DEFF Research Database (Denmark)

    Owens, T; Wekerle, H; Antel, J

    2001-01-01

    The use of transgenic technology to over-express or prevent expression of genes encoding molecules related to inflammation has allowed direct examination of their role in experimental disease. This article reviews transgenic and knockout models of CNS demyelinating disease, focusing primarily on ...

  5. Basic Concepts of CNS Development.

    Science.gov (United States)

    Nowakowski, R. S.

    1987-01-01

    The goals of this review are to: (1) provide a set of concepts to aid in the understanding of complex processes which occur during central nervous system (CNS) development; (2) illustrate how they contribute to our knowlege of adult brain anatomy; and (3) delineate how modifications of normal developmental processes may affect the structure and…

  6. CNS complications of rotavirus gastroenteritis

    International Nuclear Information System (INIS)

    Volosinova, D.

    2010-01-01

    Rotavirus infection may be accompanied by serious complications, e.g. disabilities central nervous system (CNS). Theory rotavirus penetration across the blood-brain barrier and subsequent rota-associated convulsions by the 2-year case-history of the patient. Rotavirosis minor gastrointestinal symptoms may lead to erroneous diagnosis. (author)

  7. Problems of prophylactic CNS radiotherapy in acute children's leukemia

    International Nuclear Information System (INIS)

    Bek, V.; Pribylova, O.; Abrahamova, J.; Hynieova, H.; Hrodek, O.

    1980-01-01

    The prophylactic treatment of the CNS was conducted by cobalt teletherapy of the cranium and by intrathecal application of MTX after the induction of primary remission in 70 children with acute leukemia throughout 5 years up to the end of 1978. The method of the combined radio- and chemoprophylaxis of the CNS was being changed during the years, especially as far as the radiation dose for the cranium was concerned. A detailed analysis made in a group of 59 children with the minimum interval of 18 months from the beginning of the treatment showed the best results after the application of a dose of 24 Gy/3 weeks. Following this procedure the relapse of leukemia in the CNS occurred in 9% only, whereas on the application of doses of 20 Gy and lower it occurred in 35 to 40%. On the whole 24 out of 59 children, i.e. 41%, are surviving, 35 children, i.e. 59%, died. Mostly complete, but only temporary, epilation was an invariable consequence of the irradiation of the cranium. The somnolence syndrome was only sporadically observed. It cannot be excluded, however, that some of its forms in patients discharged from hospital escaped attention. No case was recorded of serious impairment of the CNS of the leukoencephalopathic type. Up to now the psychomotor, intellectual and emotional development of the surviving children has been normal. (author)

  8. Nanomedicines for the Treatment of CNS Diseases.

    Science.gov (United States)

    Reynolds, Jessica L; Mahato, Ram I

    2017-03-01

    Targeting and delivering macromolecular therapeutics to the central nervous system (CNS) has been a major challenge. The blood-brain barrier (BBB) is the main obstacle that must be overcome to allow compounds to reach their targets in the brain. Therefore, much effort has been channelled into improving transport of therapeutics across the BBB and into the CNS including the use of nanoparticles. In this thematic issue, several reviews and original research are presented that address "Nanomedicines for CNS Diseases." The articles in this issue are concentrated on either CNS-HIV disease or CNS tumors. In regards to CNS-HIV disease, there are two reviews that discuss the role of nanoparticles for improving the delivery of HIV therapeutics to the CNS. In addition, there are two original articles focusing on therapies for CNS-HIV, one of them uses nanoparticles for delivery of siRNA specific to a key protein in autophagy to microglia, and another discusses nanoparticle delivery of a soluble mediator to suppress neuroinflammation. Furthermore, a comprehensive review about gene therapy for CNS neurological diseases is also included. Finally, this issue also includes review articles on enhanced drug targeting to CNS tumors. These articles include a review on the use of nanoparticles for CNS tumors, a review on functionalization (ligands) of nanoparticles for drug targeting to the brain tumor by overcoming BBB, and the final review discusses the use of macrophages as a delivery vehicle to CNS tumors. This thematic issue provides a wealth of knowledge on using nanomedicines for CNS diseases.

  9. Uptake of indium-111 labelled platelets by normal, nephrotic and transplanted kidneys

    International Nuclear Information System (INIS)

    Desir, G.; Lange, R.; Smith, E.; Bia, M.; Flye, M.; Kashgarian, M.; Canganelli, A.; Ezekowitz

    1984-01-01

    To determine the role of platelets in the genesis of renal transplant (T) rejection, the authors studied 3 groups of adult patients. Group I, n=8, had normal renal function (Cr=1 +- 0.1 mg%, Mean +- SD). Group II, n=9, had nephrotic syndrome (Cr=2.4 +- 1). Group III, n=7, consisted of 5 cadaveric (C) and 2 living related donor (LRD) T. In Group II, 1 patient had received a T 4 years prior to study. Group I and II received 448 +- 101 μCi and Group III 236 +- 51 μCi of Indium-111. In Groups I and II the first image was obtained 18 +- 6 hrs after injection. In Group II the first was obtained 6 +- 2 hr after injection and 1-3 times/day thereafter for a maximum of 7 days. Renal biopsies were obtained in all patients in Group III during imaging (n=5) or within 2 - 5 days of the last image. One patient was studied twice. In Group III, 5 patients received prednisone and azothiaprine and 2 prednisone and cyclosporine. Platelet uptake index (PUI) was calculated as the ratio of uptake over the T against a reference area. Rejection was diagnosed by biopsy. In groups I and II platelet uptake was seen only in the T patient. In Group III the PUI was 1.54 +- .13 in the rejecting T (n=5), 1.42 +- .2 in the non-rejecting T (n=3), 1.62 in a LRD non-rejecting T and 1.31 (n=2) in C non-rejecting T. In the four patients studied within 5 days of T the PUI was elevated at 1.47 +- .1. The authors conclude that: 1) platelets do not accumulate in normal or nephrotic native kidneys, 2) significant uptake occurs in the first week after C and LRD whether or not rejection is present, and 3) uptake in non-rejecting kidneys cannot be ascribed to perfusion induced endothelial injury since it was present in LRD transplants

  10. Applications of Genomic Sequencing in Pediatric CNS Tumors.

    Science.gov (United States)

    Bavle, Abhishek A; Lin, Frank Y; Parsons, D Williams

    2016-05-01

    Recent advances in genome-scale sequencing methods have resulted in a significant increase in our understanding of the biology of human cancers. When applied to pediatric central nervous system (CNS) tumors, these remarkable technological breakthroughs have facilitated the molecular characterization of multiple tumor types, provided new insights into the genetic basis of these cancers, and prompted innovative strategies that are changing the management paradigm in pediatric neuro-oncology. Genomic tests have begun to affect medical decision making in a number of ways, from delineating histopathologically similar tumor types into distinct molecular subgroups that correlate with clinical characteristics, to guiding the addition of novel therapeutic agents for patients with high-risk or poor-prognosis tumors, or alternatively, reducing treatment intensity for those with a favorable prognosis. Genomic sequencing has also had a significant impact on translational research strategies in pediatric CNS tumors, resulting in wide-ranging applications that have the potential to direct the rational preclinical screening of novel therapeutic agents, shed light on tumor heterogeneity and evolution, and highlight differences (or similarities) between pediatric and adult CNS tumors. Finally, in addition to allowing the identification of somatic (tumor-specific) mutations, the analysis of patient-matched constitutional (germline) DNA has facilitated the detection of pathogenic germline alterations in cancer genes in patients with CNS tumors, with critical implications for genetic counseling and tumor surveillance strategies for children with familial predisposition syndromes. As our understanding of the molecular landscape of pediatric CNS tumors continues to advance, innovative applications of genomic sequencing hold significant promise for further improving the care of children with these cancers.

  11. An invertebrate model for CNS drug discovery

    DEFF Research Database (Denmark)

    Al-Qadi, Sonia; Schiøtt, Morten; Hansen, Steen Honoré

    2015-01-01

    BACKGROUND: ABC efflux transporters at the blood brain barrier (BBB), namely the P-glycoprotein (P-gp), restrain the development of central nervous system (CNS) drugs. Consequently, early screening of CNS drug candidates is pivotal to identify those affected by efflux activity. Therefore, simple,...... barriers. CONCLUSION: Findings suggest a conserved mechanism of brain efflux activity between insects and vertebrates, confirming that this model holds promise for inexpensive and high-throughput screening relative to in vivo models, for CNS drug discovery....

  12. Oral Session 03: CNS Risk

    International Nuclear Information System (INIS)

    Narici, Livio; Nelson, Gregory A.

    2014-01-01

    Exposure to space radiation may have impacts on brain function, either during or following missions. It is most important to determine how low doses of protons and high-LET irradiation elicit changes in brain function. Within this framework, the role of oxidative stress should also be assessed, as well as other possible interaction mechanisms involving, e.g., genetic, environmental, and sex-dependent risk factors. The hippocampus is particularly susceptible to radiation. It plays an essential role in memory formation and consolidation and is one of the most investigated brain components for its responses to radiation. The hippocampus is also one of the first brain structures to be damaged in the pathogenesis of Alzheimer's disease, an important potential late impairment following irradiation. In ‘Section 3: CNS risk’, six papers have been presented focused on these issues. For details the reader is directed to the specific papers. Here a very short summary follows

  13. microRNAs in CNS disorders

    DEFF Research Database (Denmark)

    Kocerha, Jannet; Kauppinen, Sakari; Wahlestedt, Claes

    2009-01-01

    RNAs (miRNAs) have been identified in the mammalian central nervous system (CNS) and are reported to mediate pivotal roles in many aspects of neuronal functions. Disruption of miRNA-based post-transcriptional regulation has been implicated in a range of CNS disorders as one miRNA is predicted to impact...

  14. Joubert Syndrome, A Ciliopathy

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2013-10-01

    Full Text Available Investigators at Neurogenetics Unit, Mendel Laboratory, Rome, and University of Salerno, Italy, review the clinical features and genetic basis of Joubert syndrome, overlap with other ciliopathies, and the multifaceted roles of primary cilia in CNS development.

  15. CNS embryonal tumours: WHO 2016 and beyond.

    Science.gov (United States)

    Pickles, J C; Hawkins, C; Pietsch, T; Jacques, T S

    2018-02-01

    Embryonal tumours of the central nervous system (CNS) present a significant clinical challenge. Many of these neoplasms affect young children, have a very high mortality and therapeutic strategies are often aggressive with poor long-term outcomes. There is a great need to accurately diagnose embryonal tumours, predict their outcome and adapt therapy to the individual patient's risk. For the first time in 2016, the WHO classification took into account molecular characteristics for the diagnosis of CNS tumours. This integration of histological features with genetic information has significantly changed the diagnostic work-up and reporting of tumours of the CNS. However, this remains challenging in embryonal tumours due to their previously unaccounted tumour heterogeneity. We describe the recent revisions made to the 4th edition of the WHO classification of CNS tumours and review the main changes, while highlighting some of the more common diagnostic testing strategies. © 2017 British Neuropathological Society.

  16. Natural host genetic resistance to lentiviral CNS disease: a neuroprotective MHC class I allele in SIV-infected macaques.

    Directory of Open Access Journals (Sweden)

    Joseph L Mankowski

    Full Text Available Human immunodeficiency virus (HIV infection frequently causes neurologic disease even with anti-retroviral treatment. Although associations between MHC class I alleles and acquired immunodeficiency syndrome (AIDS have been reported, the role MHC class I alleles play in restricting development of HIV-induced organ-specific diseases, including neurologic disease, has not been characterized. This study examined the relationship between expression of the MHC class I allele Mane-A*10 and development of lentiviral-induced central nervous system (CNS disease using a well-characterized simian immunodeficiency (SIV/pigtailed macaque model. The risk of developing CNS disease (SIV encephalitis was 2.5 times higher for animals that did not express the MHC class I allele Mane-A*10 (P = 0.002; RR = 2.5. Animals expressing the Mane-A*10 allele had significantly lower amounts of activated macrophages, SIV RNA, and neuronal dysfunction in the CNS than Mane-A*10 negative animals (P<0.001. Mane-A*10 positive animals with the highest CNS viral burdens contained SIV gag escape mutants at the Mane-A*10-restricted KP9 epitope in the CNS whereas wild type KP9 sequences dominated in the brain of Mane-A*10 negative animals with comparable CNS viral burdens. These concordant findings demonstrate that particular MHC class I alleles play major neuroprotective roles in lentiviral-induced CNS disease.

  17. Metallothionein expression and roles in the CNS

    DEFF Research Database (Denmark)

    Penkowa, Milena

    2002-01-01

      Metallothioneins (MTs) are low-molecular-weight (6-7 kDa) nonenzymatic proteins (60-68 amino acid residues, 25-30% being cysteine) expressed ubiquitous in the animal kingdom. In the central nervous system (CNS), three MT isoforms are known, namely MT-I to MT-III. MT-I and MT-II (MT...

  18. Cowden syndrome

    Directory of Open Access Journals (Sweden)

    Ravi Prakash S

    2010-01-01

    Full Text Available Cowden syndrome or multiple hamartoma syndrome is an autosomal dominant condition with variable expressions that result mainly from mutation in the PTEN gene on arm 10q. It is characterized by multiple hamartomatous neoplasms of the skin, oral mucosa, gastrointestinal tract, bones, CNS, eyes, and genitourinary tract. Mucocutaneous features include trichilemmomas, oral mucosal papillomatosis, acral keratosis, and palmoplantar keratosis. Here we present a case of Cowden syndrome in a 14-year-old female patient with the chief complaint of multiple oral papillomatous lesions.

  19. CNS penetration of ART in HIV-infected children

    NARCIS (Netherlands)

    van den Hof, Malon; Blokhuis, Charlotte; Cohen, Sophie; Scherpbier, Henriette J.; Wit, Ferdinand W. N. M.; Pistorius, M. C. M.; Kootstra, Neeltje A.; Teunissen, Charlotte E.; Mathot, Ron A. A.; Pajkrt, Dasja

    2018-01-01

    Background: Paediatric data on CNS penetration of antiretroviral drugs are scarce. Objectives: To evaluate CNS penetration of antiretroviral drugs in HIV-infected children and explore associations with neurocognitive function. Patients and methods: Antiretroviral drug levels were measured in paired

  20. Noonan syndrome: crossed fused ectopic kidneys and focal segmental glomerulosclerosis-a rare association.

    Science.gov (United States)

    Gupta, Ankur; Khaira, Ambar; Lal, Charanjit; Mahajan, Sandeep; Tiwari, Suresh C

    2009-10-01

    Noonan syndrome is characterised by short stature, typical facial dysmorphology and congenital heart defects. Urogenital abnormalities are reported in 10% of the cases. We present a 14-year-old girl with characteristic features of Noonan syndrome and nephrotic-range proteinuria. She had crossed fused ectopic kidneys. Renal biopsy showed focal segmental glomerulosclerosis. Oral steroids were instituted and she responded well. The case highlights this novel renal presentation of Noonan syndrome.

  1. CNS adverse events associated with antimalarial agents. Fact or fiction?

    NARCIS (Netherlands)

    Phillips-Howard, P. A.; ter Kuile, F. O.

    1995-01-01

    CNS adverse drug events are dramatic, and case reports have influenced clinical opinion on the use of antimalarials. Malaria also causes CNS symptoms, thus establishing causality is difficult. CNS events are associated with the quinoline and artemisinin derivatives. Chloroquine, once considered too

  2. Therapeutic potential of agmatine for CNS disorders.

    Science.gov (United States)

    Neis, Vivian B; Rosa, Priscila B; Olescowicz, Gislaine; Rodrigues, Ana Lúcia S

    2017-09-01

    Agmatine is a neuromodulator that regulates multiple neurotransmitters and signaling pathways. Several studies have focused on elucidating the mechanisms underlying the neuroprotective effects of this molecule, which seems to be mediated by a reduction in oxidative damage, neuroinflammation, and proapoptotic signaling. Since these events are implicated in acute and chronic excitotoxicity-related disorders (ischemia, epilepsy, traumatic brain injury, spinal cord injury, neurodegenerative, and psychiatric disorders) as well as in nociception, agmatine has been proposed as a therapeutic strategy for the treatment of central nervous system (CNS) disorders. Agmatine also stimulates the expression of trophic factors and adult neurogenesis, contributing to its ability to induce endogenous repair mechanisms. Therefore, considering its wide range of biological effects, this review summarizes the current knowledge about its protective and regenerative properties in the CNS. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Interneuron progenitor transplantation to treat CNS dysfunction

    Directory of Open Access Journals (Sweden)

    Muhammad O Chohan

    2016-08-01

    Full Text Available Due to the inadequacy of endogenous repair mechanisms diseases of the nervous system remain a major challenge to scientists and clinicians. Stem cell based therapy is an exciting and viable strategy that has been shown to ameliorate or even reverse symptoms of CNS dysfunction in preclinical animal models. Of particular importance has been the use of GABAergic interneuron progenitors as a therapeutic strategy. Born in the neurogenic niches of the ventral telencephalon, interneuron progenitors retain their unique capacity to disperse, integrate and induce plasticity in adult host circuitries following transplantation. Here we discuss the potential of interneuron based transplantation strategies as it relates to CNS disease therapeutics. We also discuss mechanisms underlying their therapeutic efficacy and some of the challenges that face the field.

  4. Treatment options for Primary CNS Lymphoma.

    Science.gov (United States)

    Laghari, Altaf Ali; Ahmed, Syed Ijlal; Jabbar, Adnan; Shamim, Muhammad Shahzad

    2018-03-01

    Primary CNS lymphoma (PCNSL) is a rare and aggressive brain tumour that is uniformly fatal. The rarity of the disease and the poor response to treatment makes it difficult to reach a consensus with regards to treatment options. In this review, the authors have discussed different treatment modalities used in the management of PCNSL including chemotherapy, surgery and radiation, as well as the results of recent clinical trials on treatment options for PCNSL.

  5. Engineering progress of CNS concept in Hanaro

    International Nuclear Information System (INIS)

    Choi, C.O.; Park, K.N.; Park, S.H.

    1997-01-01

    The Korea Atomic Energy research Institute (KAERI) strives to provide utilizing facilities on and around the Hanaro reactor in order to activate advanced researches by neutron application. As one of the facilities to be installed, the conceptual design work of CNS was started in 1996 with a project schedule of 5 years so that its installation work can be finished by the year 2000. And the major engineering targets of this CNS facility are established for a minimum physical interference with the present facilities of the Hanaro, a reach-out of very-high-gain factors in the cold neutron flux, a simplicity of the maintenance of the facility, and a safety in the operation of the facility as well as the reactor. For the conceptual design of Hanaro CNS, the experience of utilization and production of cold neutron at WWR-M reactor Gatchina, Russia has been used with that of elaborations for PIK reactor in design for neutron guide systems and instruments. (author)

  6. A low-protein diet restricts albumin synthesis in nephrotic rats.

    OpenAIRE

    Kaysen, G A; Jones, H; Martin, V; Hutchison, F N

    1989-01-01

    High-protein diets increase albumin synthesis in rats with Heymann nephritis but albuminuria increases also, causing serum albumin concentration to be suppressed further than in nephrotic animals eating a low-protein diet. Experiments were designed to determine whether dietary protein augmentation directly stimulates albumin synthesis, or whether instead increased albumin synthesis is triggered by the decrease in serum albumin concentration. Evidence is presented that dietary protein augmenta...

  7. Prophylactic CNS therapy in childhood leukemia

    International Nuclear Information System (INIS)

    Yokoyama, Takashi; Hiyoshi, Yasuhiko; Fujimoto, Takeo

    1982-01-01

    This study was designed to evaluate the efficacy of CNS-prophylaxis with high-dose methotrexate (MTX). Seventy children with previously untreated acute lymphoblastic leukemia (ALL) entered to this study between July 1978 and December 1980. According to initial white blood count (WBC), they were stratified to induce remission with; vincristine and prednine in low initial WBC ( lt 25,000/mm 3 ) group and these two agents plus adriamycin in high initial WBC ( gt 25,000/mm 3 ) group. After inducing remission, 62 children who achieved CR, received different CNS-prophlaxis; using a regimen of three doses of weekly high-dose MTX (1,000 mg/m 2 ) 6-hour infusion, which was repeated every 12 weeks-Group A (n = 14); high-dose MTX followed by 2400 rad cranial irradiation plus three doses of i.t. MT X-Group B (n = 15), 2400 rad cranial irradiation plus three doses of i.t. MTX-Group C (n = 16), and in 17 patients with high initial WBC, same as in Group A-Group D (n = 17). During an intravenous 6-h infusion of MTX at a dose of 1,000 mg/m 2 , the CSF concentration of MTX rose to 2.3 +- 2.4 x 10 -6 M after initiation of infusion and remained in 10 -7 M level for 48 hours. CNS-leukemia terminated complete remission in one of 14 children in Group A, two of 15 in Group B, two of 16 in Group C and two of 17 in Group D. The cumulative incidence of CNS-leukemia at 20 months calculated by the technique of Kaplan and Meier was 0% i n Group A, 18.1% in Group B, 7.1% in Group C and 50.8% in Group D. There was no statistical difference among Groups A, B and C. These data suggested that CNS-prophylaxis with high-dose intravenous MTX was effective as well as 2400 rad cranial irradiation plus three doses of i.t. MTX in childhood ALL with low initial WBC. (author)

  8. [Simvastatin therapy and effect on hiperlipidemia and vascular status in nephrotic children with sustained dyslipidemia].

    Science.gov (United States)

    Ksiazek, Joanna; Niemirska, Anna; Lipka, Maria; Wierzbicka, Aldona; Syczewska, Małgorzata; Grenda, Ryszard

    2009-03-01

    Dyslipidemia is common in nephrotic children and persistent lipid abnormalities are risk factor of late vascular complications. The aim of the study was evaluation of efficacy and safety of 12-months simvastatin therapy in nephrotic children with lipid profile abnormalities present despite clinical remission lasting for at least 8 weeks, including ultrasonographic assessment of carotid and femoral arteries. Overall 52 children (40 steroid-dependent and 12 steroid-resistant) were initially introduced to the study and 29 of them were treated with simvastatin. Normalisation of lipid profile was achieved in 19/29 (65.5%) and improvement in 9/29 (31%). Significant reduction in total cholesterol (p 2.0) was small. Increased cIMT was seen at baseline in 4 patients and in 5 after simvastatin treatment, however average and Z-score values in children under simvastatin treatment have decreased. Increased fIMT values were seen at baseline in 2 and in one case after simvastatin treatment. Tolerance of simvastation was very good in all cases but one. Simvastatin therapy was effective and safe in nephrotic non-proteinuric children with abnormal lipid profile. Fair estimation of impact of the 12-months simvastatin therapy on vascular status was not available due to limited number of children with significantly increased IMT at baseline.

  9. SINS/CNS Nonlinear Integrated Navigation Algorithm for Hypersonic Vehicle

    Directory of Open Access Journals (Sweden)

    Yong-jun Yu

    2015-01-01

    Full Text Available Celestial Navigation System (CNS has characteristics of accurate orientation and strong autonomy and has been widely used in Hypersonic Vehicle. Since the CNS location and orientation mainly depend upon the inertial reference that contains errors caused by gyro drifts and other error factors, traditional Strap-down Inertial Navigation System (SINS/CNS positioning algorithm setting the position error between SINS and CNS as measurement is not effective. The model of altitude azimuth, platform error angles, and horizontal position is designed, and the SINS/CNS tightly integrated algorithm is designed, in which CNS altitude azimuth is set as measurement information. GPF (Gaussian particle filter is introduced to solve the problem of nonlinear filtering. The results of simulation show that the precision of SINS/CNS algorithm which reaches 130 m using three stars is improved effectively.

  10. CNS-syndrome. Characterization of rat brain intermediate filaments

    International Nuclear Information System (INIS)

    Nedzvetskij, V.S.; Busygina, S.G.; Berezin, V.A.; Dvoretskij, A.I.

    1990-01-01

    A study was made of the effect of ionizing radiation on the content and polypeptide composition of filamentous and soluble glial fibrillary acidic protein (GFAP) in different regions of rat brain. Ionizing radiation was shown to decrease considerably the level of soluble GFAP in cerebral cortex, cerebellum, middle brain and hippocampus. Polypeptide composition of soluble GFAP detected by the immonublot-method was found to be changed considerably in different brain areas of irradiated animals

  11. Immune regulation and CNS autoimmune disease

    DEFF Research Database (Denmark)

    Antel, J P; Owens, T

    1999-01-01

    The central nervous system is a demonstrated target of both clinical and experimental immune mediated disorders. Immune regulatory mechanisms operative at the levels of the systemic immune system, the blood brain barrier, and within the CNS parenchyma are important determinants of the intensity...... and duration of the tissue directed injury. Convergence of research, involving direct manipulation of specific cells and molecular mediators in animal models and in vitro analysis of human immune and neural cells and tissues, is providing increasing insight into the role of these immune regulatory functions...

  12. Malaria falciparum y síndrome nefrótico: nuestras experiencias Falciparum malaria and nephrotic Síndrome: Our experience

    Directory of Open Access Journals (Sweden)

    Jesús Juan Rodríguez

    2007-03-01

    Full Text Available Las especies de Plasmodium que infectan al hombre son: P. vivax, P. Malariae, P. Ovale y P. Falciparum. En Mozambique, como en la mayor parte de la llamada África Subsahariana, la especie predominante es P. falciparum cloroquina resistente. La infección por P. falciparum es potencialmente mortal, tiende a manifestarse como una enfermedad febril sin signos localizados o específicos. En los casos más graves, sin embargo puede presentarse asociada a variados síndromes clínicos que plantean serios retos terapéuticos.Es reconocido que la malaria o paludismo puede asociarse a síndrome nefrótico y se han dado explicaciones de esta relación patogénica. En Mozambique, en un período de seis meses, tuvimos la oportunidad de tratar tres casos de Malaria falciparum grave, asociado a síndrome nefrótico.Divulgar y trasmitir las experiencias prácticas y consideraciones teóricas a propósito de uno de estos casos es la motivación de los autores de este trabajo.Plasmodiumspecies infecting man are the following: P.vivax, P. Malariae, P. Ovale and P. Falciparum. In Mozambique, like the biggest area from the so called Subsaharian Africa,the resistent-chloroquine P. Falciparum is the predominating specie in this area. The P. Falciparum infection is potentially fatal, with a trend to show as a febrile condition with no localized or specific signs. In more severe cases, however, it may be presented in association with different clinical syndromes which represent serious therapeutic challenges. It is not unknown that Malaria or Paludism may be associated with the Nephrotic Syndrome, and many explanations have been given on this pathogenic relatioship. In a sixth month's period in Mozambique we had the chance to test three severe cases of Falciparum Malaria associated with a Nephrotic Syndrome. Spreading the practical experience and theoretic considerations on one of these cases is the aim of this work.

  13. Novel agents in CNS myeloma treatment.

    Science.gov (United States)

    Gozzetti, Alessandro; Cerase, Alfonso

    2014-01-01

    Central nervous system localization of multiple myeloma (CNS-MM) accounts for about 1% of all MM.Treatment is still unsatisfactory. Many treatments have been described in the literature: chemotherapy (CHT), intrathecal therapy (IT), and radiotherapy (RT), with survivals reported between one month and six months. Recent drugs such as the immunomodulatory drugs (IMiDs) and proteasome inhibitors (bortezomib) have changed the treatment of patients with MM, both younger and older, with a significant improvement in response and survival. The activity of new drugs in CNSMM has been reported but is still not well known. Bortezomib does not cross the blood brain barrier (BBB), and IMID’s seem to have only a minimal crossover. The role of novel agents in CNS MM management will be discussed as well as the potential role of other new immunomodulatory drugs (pomalidomide) and proteasome inhibitors that seem to cross the BBB and hold promise into the treatment of this rare and still incurable localization of the disease.

  14. Malignant lymphoma in central nervous system (CNS)

    International Nuclear Information System (INIS)

    Fujiyoshi, Kenji; Fukuyama, Hidenao; Akiguchi, Ichiro; Kameyama, Masakuni; Nishimura, Toshio.

    1984-01-01

    A 71-year-old male was admitted to Kohka Public Hospital on January 4, 1980, because of frequent vomiting and recent memory loss. Two weeks before admission upper G-I series showed no abnormalities. Physical and neurological examinations revealed no abnormalities except for slightly apathetic appearance and recent memory loss. Mild pleocytosis and marked increase of protein in CSF were observed. CT scan on January 17 showed high density areas in both medial sides of temporal lobes with remarkable contrast enhancement. His memory and, consciousness disturbances gradually aggravated, accompanied by abnormal density spreading around the ventricle walls like ventriculitis. He was transfered to Kyoto University Hospital on March 17, and malignant lymphoma was diagnosed on the basis of CSF cytology. Radiation and chemotherapy alleviated the CNS involvement and he regained normal mental function. On June 16, he developed pneumonia followed by status epilepticus. Autopsy findings revealed no lymphoid cell infiltration, but fibrous tissues in both hippocampal gyri and lymphomatous cells in the liver, which could not be suspected on clinical examinations. Apparent malignant lymphoma cells were not found in lymph nodes. This case indicated peculiar evolution of malignant lymphoma from liver to CNS or vice versa. We could not decide which organ was primary. CT findings of this case was very interesting; they resembled ventriculitis, which simulate tumors such as medulloblastoma or ependymoma spreading under ependymal lining. (author)

  15. The imaging appearances of intracranial CNS infections in adult HIV and AIDS patients

    Energy Technology Data Exchange (ETDEWEB)

    Offiah, C.E. [Department of Neuroradiology, Hope Hospital, Stott Lane, Salford, Manchester (United Kingdom)]. E-mail: chockycj@yahoo.co.uk; Turnbull, I.W. [Department of Neuroradiology, Hope Hospital, Stott Lane, Salford, Manchester (United Kingdom)

    2006-05-15

    The spectrum of pathology affecting the central nervous system (CNS) in patients suffering from acquired immunodeficiency syndrome (AIDS) is broad and comprises predominantly opportunistic infections and neoplasms. It is estimated that approximately one-third of all patients with AIDS develop neurological complications. The organisms responsible for AIDS are human retroviruses: primarily the human immunodeficiency virus type 1 (HIV). In this review we shall focus on the neurological complications of HIV and AIDS which are applicable to the more frequently occurring intracranial infective organisms. Attention will be paid specifically to those CNS manifestations occurring in the adult HIV and AIDS population as infection in the paediatric HIV and AIDS group, although bearing some similarities, demonstrates some important differences.

  16. The imaging appearances of intracranial CNS infections in adult HIV and AIDS patients

    International Nuclear Information System (INIS)

    Offiah, C.E.; Turnbull, I.W.

    2006-01-01

    The spectrum of pathology affecting the central nervous system (CNS) in patients suffering from acquired immunodeficiency syndrome (AIDS) is broad and comprises predominantly opportunistic infections and neoplasms. It is estimated that approximately one-third of all patients with AIDS develop neurological complications. The organisms responsible for AIDS are human retroviruses: primarily the human immunodeficiency virus type 1 (HIV). In this review we shall focus on the neurological complications of HIV and AIDS which are applicable to the more frequently occurring intracranial infective organisms. Attention will be paid specifically to those CNS manifestations occurring in the adult HIV and AIDS population as infection in the paediatric HIV and AIDS group, although bearing some similarities, demonstrates some important differences

  17. Behavioral and Genetic Evidence for GIRK Channels in the CNS: Role in Physiology, Pathophysiology, and Drug Addiction.

    Science.gov (United States)

    Mayfield, Jody; Blednov, Yuri A; Harris, R Adron

    2015-01-01

    G protein-coupled inwardly rectifying potassium (GIRK) channels are widely expressed throughout the brain and mediate the inhibitory effects of many neurotransmitters. As a result, these channels are important for normal CNS function and have also been implicated in Down syndrome, Parkinson's disease, psychiatric disorders, epilepsy, and drug addiction. Knockout mouse models have provided extensive insight into the significance of GIRK channels under these conditions. This review examines the behavioral and genetic evidence from animal models and genetic association studies in humans linking GIRK channels with CNS disorders. We further explore the possibility that subunit-selective modulators and other advanced research tools will be instrumental in establishing the role of individual GIRK subunits in drug addiction and other relevant CNS diseases and in potentially advancing treatment options for these disorders. © 2015 Elsevier Inc. All rights reserved.

  18. CNS fungal meningitis to the "Top of the basilar"

    Institute of Scientific and Technical Information of China (English)

    Logan CS; Kirschner RC; Simonds GR

    2013-01-01

    Central nervous system(CNS) infections are a rare complication of epidural steroid injections and without strong clinical suspicion, fungal organisms may be overlooked among the long differential of causes of meningitis.Rare sequela of fungal meningitis is the development of stroke.To our knowledge, we present the first case of post epidural steroid injection(ESI) fungal meningitis leading toa basilar artery stroke, otherwise known as“top of the basilar” syndrome.We present a49-year-old female with a history ofESIs who presented to the emergency department with headache, neck stiffness, and abdominal pain.She was discharged after her labs and symptoms were deemed inconsistent with meningitis.She was eventually admitted and twelve days after her originalED visit, she was diagnosed with meningitis and started on anti-fungal treatment.She was discharged88 days later but was readmitted due to left sided weakness and mental status changes.She quickly lost motor and bulbar functions.AnMRA showed diminished distal flow through the basilar artery, suggesting near complete occlusion.Although appropriate long term anti-fungal treatment was started, the patient still succumbed to a rare vascular event.Physicians who are treating patients forESI meningitis should be aware of the potential for vasculitic and encephalitic complications.

  19. Transplanting oligodendrocyte progenitors into the adult CNS

    International Nuclear Information System (INIS)

    Franklin, R.J.M.; Blakemore, W.F.; Cambridge Univ.

    1997-01-01

    This review covers a number of aspects of the behaviour of oligodendrocyte progenitors following transplantation into the adult CNS. First, an account is given of the ability of transplanted oligodendrocyte progenitors, grown in tissue culture in the presence of PDGF and bFGF, to extensively remyelinate focal areas of persistent demyelination. Secondly, we describe how transplanted clonal cell lines of oligodendrocyte progenitors will differentiate in to astrocytes as will oligodendrocytes following transplantation into pathological environments in which both oligodendrocytes and astrocytes are absent, thereby manifesting the bipotentially demonstrable in vitro but not during development. Finally, a series of studies examining the migratory behaviour of transplanted oligodendrocyte progenitors (modelled using the oligodendrocyte progenitor cell line CG4) are described. (author)

  20. Biomarkers for CNS involvement in pediatric lupus

    Science.gov (United States)

    Rubinstein, Tamar B; Putterman, Chaim; Goilav, Beatrice

    2015-01-01

    CNS disease, or central neuropsychiatric lupus erythematosus (cNPSLE), occurs frequently in pediatric lupus, leading to significant morbidity and poor long-term outcomes. Diagnosing cNPSLE is especially difficult in pediatrics; many current diagnostic tools are invasive and/or costly, and there are no current accepted screening mechanisms. The most complicated aspect of diagnosis is differentiating primary disease from other etiologies; research to discover new biomarkers is attempting to address this dilemma. With many mechanisms involved in the pathogenesis of cNPSLE, biomarker profiles across several modalities (molecular, psychometric and neuroimaging) will need to be used. For the care of children with lupus, the challenge will be to develop biomarkers that are accessible by noninvasive measures and reliable in a pediatric population. PMID:26079959

  1. Palmitoylethanolamide in CNS health and disease.

    Science.gov (United States)

    Mattace Raso, Giuseppina; Russo, Roberto; Calignano, Antonio; Meli, Rosaria

    2014-08-01

    The existence of acylethanolamides (AEs) in the mammalian brain has been known for decades. Among AEs, palmitoylethanolamide (PEA) is abundant in the central nervous system (CNS) and conspicuously produced by neurons and glial cells. Antihyperalgesic and neuroprotective properties of PEA have been mainly related to the reduction of neuronal firing and to control of inflammation. Growing evidence suggest that PEA may be neuroprotective during CNS neurodegenerative diseases. Advances in the understanding of the physiology and pharmacology of PEA have potentiated its interest as useful biological tool for disease management. Several rapid non-genomic and delayed genomic mechanisms of action have been identified for PEA as peroxisome proliferator-activated receptor (PPAR)-α dependent. First, an early molecular control, through Ca(+2)-activated intermediate- and/or big-conductance K(+) channels opening, drives to rapid neuronal hyperpolarization. This is reinforced by the increase of the inward Cl(-) currents due to the modulation of the gamma aminobutyric acid A receptor and by the desensitization of the transient receptor potential channel type V1. Moreover, the gene transcription-mediated mechanism sustains the long-term anti-inflammatory effects, by reducing pro-inflammatory enzyme expression and increasing neurosteroid synthesis. Overall, the integration of these different modes of action allows PEA to exert an immediate and prolonged efficacious control in neuron signaling either on inflammatory process or neuronal excitability, maintaining cellular homeostasis. In this review, we will discuss the effect of PEA on metabolism, behavior, inflammation and pain perception, related to the control of central functions and the emerging evidence demonstrating its therapeutic efficacy in several neurodegenerative diseases. Copyright © 2014. Published by Elsevier Ltd.

  2. Genetic mutation in Egyptian children with steroid-resistant nephrotic syndrome

    Directory of Open Access Journals (Sweden)

    Manal Micheal Thomas

    2018-01-01

    Conclusion: Our study concludes that mutations of NPHS2 gene are common among Egyptian children with SRNS. We support a model where ethnicity plays an important role in specific NPHS2 mutations, since a novel mutation was found in one patient in this study. Future study on a large number of Egyptian patients with SRNS is warranted to identify the actual genetic contribution of this gene in the development of SRNS in our population, which might help in patients' prognosis and management.

  3. Evaluation of Right Ventricle Function in Children With Primary Nephrotic Syndrome

    Directory of Open Access Journals (Sweden)

    Qiang Qin

    2010-06-01

    Conclusion: Right ventricle function was impaired in children with PNS. The characteristics were unrelated to blood pressure and IGF-1, but may be correlated with TNF-α and disease duration. Further studies are needed to evaluate the etiology and clinical implications of this abnormality.

  4. Cholecystitis and nephrotic syndrome complicating Epstein-Barr virus primary infection.

    Science.gov (United States)

    Rodà, Diana; Huici, Malka; Ricart, Sílvia; Vila, Jordi; Fortuny, Clàudia; Alsina, Laia

    2017-02-01

    Epstein-Barr virus (EBV) infection results in a spectrum of clinical manifestations. The host immune response to EBV plays a key role in the extent and degree of clinical features, which in children under 4 years of age are usually mild, non-specific and self-limiting. A 2-year-old boy in whom no known immune disorder could be found presented with acute acalculous cholecystitis, renal dysfunction with massive proteinuria, ascites, pleural effusion, minimal peripheral oedema and a severe systemic inflammatory response. Improvement occurred after initiation of corticosteroids and antiviral treatment with gancyclovir. In severely symptomatic or complicated EBV infection, a primary immunodeficiency must be suspected. If a primary immunodeficiency has been ruled out, the correct management of severe EBV infection in the immunocompetent host remains controversial.

  5. Is biopsy required prior to cyclophosphamide in steroid-sensitive nephrotic syndrome?

    NARCIS (Netherlands)

    Stadermann, M.B.; Lilien, M.R.; Kar, N.C.A.J. van de; Monnens, L.A.H.; Schröder, C.H.

    2003-01-01

    AIM: The present studywas designed to retrospectively evaluate the use of renal biopsies prior to cyclophosphamide therapy. The aim of the study was to determine in how many cases histological outcome of the biopsies had subsequently changed the decision to treat or refrain from treatment. PATIENTS

  6. Efficacy and Safety of Rituximab in Children with Refractory Nephrotic Syndrome; A Multicenter Clinical Trial

    Directory of Open Access Journals (Sweden)

    Yo Han Ahn

    2014-06-01

    Conclusions: In this interim analysis of clinical trial to evaluate the efficacy and safety of RTX in children with refractory NS, RTX treatment for refractory NS was safe and effective, especially in patients with DNS.

  7. A circadian rhythm of proteinuria in patients with a nephrotic syndrome

    NARCIS (Netherlands)

    Koopman, M. G.; Krediet, R. T.; Zuyderhoudt, F. J.; de Moor, E. A.; Arisz, L.

    1985-01-01

    Circadian variations in proteinuria were studied in 17 patients with different types of glomerulopathies. During 3-4 successive days urine was collected over periods of 3 h under standardized conditions. Thirteen of the 17 patients showed a circadian rhythm of their proteinuria with a maximum

  8. Type-1 diabetes mellitus, nephrotic syndrome, and vur with ace gene polymorphism

    International Nuclear Information System (INIS)

    Kiani, I.G.; Mansoor, Q.; Ismail, M.; Khan, A.N.; Butt, G.

    2012-01-01

    Objectives: To determine sensitivity, specificity and other operating characteristics of bedside three-point compression ultrasonography performed in emergency department by emergency physicians in comparison with duplex ultrasonography. Methods: The cross-sectional study at Rasoul-e-Akram Hospital in Tehran, Iran, prospectively evaluated 81 suspected patients of lower extremity deep vein thrombosis between March 2006 and March 2007. A trained second-year resident and one attending physician of emergency medicine evaluated the veins of all the patients with through compression ultrasonography. Then, a second-year resident of radiology assessed the patients with duplex ultrasonography. Finally, data were compared and quantitative and categorical variables were worked out along with other statistical analysis through SPSS version 16. Results: The mean age of the patients was 47.2 +- 18.6 years. When cases who lost the compressibility of at least one of their femoral or popliteal veins were considered to be positive, there were 80.2% diagnosed by compression ultrasonography and 79% by the duplex variety. Sensitivity, specificity and accuracy of the former in comparison with the latter were 85.9%, 41.2% and 84.6% respectively. Conclusion: Compression ultrasonography has relatively an acceptable sensitivity and accuracy level, but has low specificity in the diagnosis of deep vein thrombosis in the hands of Iranian emergency physicians. It is better to implement duplex ultrasonography whenever accessible. Otherwise, compression ultrasonography results should be compared with the results of duplex ultrasonography as soon as possible. (author)

  9. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

    DEFF Research Database (Denmark)

    Sturm, Dominik; Orr, Brent A; Toprak, Umut H

    2016-01-01

    with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration...

  10. A philosophy for CNS radiotracer design.

    Science.gov (United States)

    Van de Bittner, Genevieve C; Ricq, Emily L; Hooker, Jacob M

    2014-10-21

    Decades after its discovery, positron emission tomography (PET) remains the premier tool for imaging neurochemistry in living humans. Technological improvements in radiolabeling methods, camera design, and image analysis have kept PET in the forefront. In addition, the use of PET imaging has expanded because researchers have developed new radiotracers that visualize receptors, transporters, enzymes, and other molecular targets within the human brain. However, of the thousands of proteins in the central nervous system (CNS), researchers have successfully imaged fewer than 40 human proteins. To address the critical need for new radiotracers, this Account expounds on the decisions, strategies, and pitfalls of CNS radiotracer development based on our current experience in this area. We discuss the five key components of radiotracer development for human imaging: choosing a biomedical question, selection of a biological target, design of the radiotracer chemical structure, evaluation of candidate radiotracers, and analysis of preclinical imaging. It is particularly important to analyze the market of scientists or companies who might use a new radiotracer and carefully select a relevant biomedical question(s) for that audience. In the selection of a specific biological target, we emphasize how target localization and identity can constrain this process and discuss the optimal target density and affinity ratios needed for binding-based radiotracers. In addition, we discuss various PET test-retest variability requirements for monitoring changes in density, occupancy, or functionality for new radiotracers. In the synthesis of new radiotracer structures, high-throughput, modular syntheses have proved valuable, and these processes provide compounds with sites for late-stage radioisotope installation. As a result, researchers can manage the time constraints associated with the limited half-lives of isotopes. In order to evaluate brain uptake, a number of methods are available

  11. Fifth CNS international steam generator conference

    International Nuclear Information System (INIS)

    2006-01-01

    The Fifth CNS International Steam Generator Conference was held on November 26-29, 2006 in Toronto, Ontario, Canada. In contrast with other conferences which focus on specific aspects, this conference provided a wide ranging forum on nuclear steam generator technology from life-cycle management to inspection and maintenance, functional and structural performance characteristics to design architecture. The 5th conference has adopted the theme: 'Management of Real-Life Equipment Conditions and Solutions for the Future'. This theme is appropriate at a time of transition in the industry when plants are looking to optimize the performance of existing assets, prevent costly degradation and unavailability, while looking ahead for new steam generator investments in life-extension, replacements and new-build. More than 50 technical papers were presented in sessions that gave an insight to the scope: life management strategies; fouling, cleaning and chemistry; replacement strategies and new build design; materials degradation; condition assessment/fitness for service; inspection advancements and experience; and thermal hydraulic performance

  12. Analysis of perfusion weighted image of CNS lymphoma

    International Nuclear Information System (INIS)

    Lee, In Ho; Kim, Sung Tae; Kim, Hyung-Jin; Kim, Keon Ha; Jeon, Pyoung; Byun, Hong Sik

    2010-01-01

    Purpose: It is difficult to differentiate CNS lymphoma from other tumors such as malignant gliomas, metastases, or meningiomas with conventional MR imaging, because the imaging findings are overlapped between these tumors. The purpose of this study is to investigate the perfusion weighted MR imaging findings of CNS lymphomas and to compare the relative cerebral blood volume ratios between CNS lymphomas and other tumors such as high grade gliomas, metastases, or meningiomas. Materials and methods: We retrospectively reviewed MRI findings and clinical records in 13 patients with pathologically proven CNS lymphoma between January 2006 and November 2008. We evaluated the relative cerebral blood volume ratios of tumor, which were obtained by dividing the values obtained from the normal white matter on MRI. Results: Total 13 patients (M:F = 8:5; age range 46-67 years, mean age 52.3 years) were included. The CNS lymphomas showed relatively low values of maximum relative CBV ratio in most patients regardless of primary or secondary CNS lymphoma. Conclusion: Perfusion weighted image may be helpful in the diagnosis of CNS lymphoma in spite of primary or secondary or B cell or T cell.

  13. 3rd ENRI International Workshop on ATM/CNS

    CERN Document Server

    2014-01-01

    The Electronic Navigation Research Institute (ENRI) held its third International Workshop on ATM / CNS in 2013 with the theme of "Drafting the future sky". There is worldwide activity taking place in the research and development of modern air traffic management (ATM) and its enabling technologies in Communication, Navigation and Surveillance (CNS). Pioneering work is necessary to contribute to the global harmonization of air traffic management and control. At this workshop, leading experts in  research, industry and academia from around the world met to share their ideas and approaches on ATM/CNS related topics.

  14. Autoimmune process in CNS under Cs-137 inner irradiation

    International Nuclear Information System (INIS)

    Lisyany, N.I.; Liubich, L.D.

    1996-01-01

    Autoimmune hypothesis as to the development of radiation-induced brain injuries stands high among the concepts of the CNS post-radiation damage pathogenesis. To study the changes occurring in a living organism affected by a small-dose radiation due to incorporated radionuclides as well as to create adequate models are of critical importance in the post-Chernobyl period. The effects of chronic small-dose inner radiation on the development of autoimmune responses were evaluated by determining the level of the CNS proteins and protein-induced antibodies to the CNS components. (author)

  15. Convulsant bicuculline modifies CNS muscarinic receptor affinity

    Directory of Open Access Journals (Sweden)

    Rodríguez de Lores Arnaiz Georgina

    2006-04-01

    Full Text Available Abstract Background Previous work from this laboratory has shown that the administration of the convulsant drug 3-mercaptopropionic acid (MP, a GAD inhibitor, modifies not only GABA synthesis but also binding of the antagonist [3H]-quinuclidinyl benzilate ([3H]-QNB to central muscarinic receptors, an effect due to an increase in affinity without modifications in binding site number. The cholinergic system has been implicated in several experimental epilepsy models and the ability of acetylcholine to regulate neuronal excitability in the neocortex is well known. To study the potential relationship between GABAergic and cholinergic systems with seizure activity, we analyzed the muscarinic receptor after inducing seizure by bicuculline (BIC, known to antagonize the GABA-A postsynaptic receptor subtype. Results We analyzed binding of muscarinic antagonist [3H]-QNB to rat CNS membranes after i.p. administration of BIC at subconvulsant (1.0 mg/kg and convulsant (7.5 mg/kg doses. Subconvulsant BIC dose failed to develop seizures but produced binding alteration in the cerebellum and hippocampus with roughly 40% increase and 10% decrease, respectively. After convulsant BIC dose, which invariably led to generalized tonic-clonic seizures, binding increased 36% and 15% to cerebellar and striatal membranes respectively, but decreased 12% to hippocampal membranes. Kd value was accordingly modified: with the subconvulsant dose it decreased 27% in cerebellum whereas it increased 61% in hippocampus; with the convulsant dose, Kd value decreased 33% in cerebellum but increased 85% in hippocampus. No change in receptor number site was found, and Hill number was invariably close to unity. Conclusion Results indicate dissimilar central nervous system area susceptibility of muscarinic receptor to BIC. Ligand binding was modified not only by a convulsant BIC dose but also by a subconvulsant dose, indicating that changes are not attributable to the seizure process

  16. Air pollution: mechanisms of neuroinflammation and CNS disease.

    Science.gov (United States)

    Block, Michelle L; Calderón-Garcidueñas, Lilian

    2009-09-01

    Air pollution has been implicated as a chronic source of neuroinflammation and reactive oxygen species (ROS) that produce neuropathology and central nervous system (CNS) disease. Stroke incidence and Alzheimer's and Parkinson's disease pathology are linked to air pollution. Recent reports reveal that air pollution components reach the brain; systemic effects that impact lung and cardiovascular disease also impinge upon CNS health. While mechanisms driving air pollution-induced CNS pathology are poorly understood, new evidence suggests that microglial activation and changes in the blood-brain barrier are key components. Here we summarize recent findings detailing the mechanisms through which air pollution reaches the brain and activates the resident innate immune response to become a chronic source of pro-inflammatory factors and ROS, culminating in CNS disease.

  17. A map of taste neuron projections in the Drosophila CNS

    Indian Academy of Sciences (India)

    2014-07-08

    Jul 8, 2014 ... information that they represent. The extensive ... physiology and behaviour in the wild type and in these mutants .... taste information is processed in the CNS. 2. ..... gene affecting the specificity of the chemosensory neurons of.

  18. Pharmacokinetic, Pharmacogenetic, and Other Factors Influencing CNS Penetration of Antiretrovirals

    Directory of Open Access Journals (Sweden)

    Jacinta Nwamaka Nwogu

    2016-01-01

    Full Text Available Neurological complications associated with the human immunodeficiency virus (HIV are a matter of great concern. While antiretroviral (ARV drugs are the cornerstone of HIV treatment and typically produce neurological benefit, some ARV drugs have limited CNS penetration while others have been associated with neurotoxicity. CNS penetration is a function of several factors including sieving role of blood-brain and blood-CSF barriers and activity of innate drug transporters. Other factors are related to pharmacokinetics and pharmacogenetics of the specific ARV agent or mediated by drug interactions, local inflammation, and blood flow. In this review, we provide an overview of the various factors influencing CNS penetration of ARV drugs with an emphasis on those commonly used in sub-Saharan Africa. We also summarize some key associations between ARV drug penetration, CNS efficacy, and neurotoxicity.

  19. CNS Involvement in AML Patient Treated with 5-Azacytidine

    Directory of Open Access Journals (Sweden)

    Diamantina Vasilatou

    2014-01-01

    Full Text Available Central nervous system (CNS involvement in acute myeloid leukemia (AML is a rare complication of the disease and is associated with poor prognosis. Sometimes the clinical presentation can be unspecific and the diagnosis can be very challenging. Here we report a case of CNS infiltration in a patient suffering from AML who presented with normal complete blood count and altered mental status.

  20. CNS-directed gene therapy for lysosomal storage diseases

    OpenAIRE

    Sands, Mark S; Haskins, Mark E

    2008-01-01

    Lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders usually caused by deficient activity of a single lysosomal enzyme. As most lysosomal enzymes are ubiquitously expressed, a deficiency in a single enzyme can affect multiple organ systems, including the central nervous system (CNS). At least 75% of all LSDs have a significant CNS component. Approaches such as bone marrow transplantation (BMT) or enzyme replacement therapy (ERT) can effectively treat the systemic dis...

  1. Sleep disorders in children after treatment for a CNS tumour.

    Science.gov (United States)

    Verberne, Lisa M; Maurice-Stam, Heleen; Grootenhuis, Martha A; Van Santen, Hanneke M; Schouten-Van Meeteren, Antoinette Y N

    2012-08-01

    The long-term survival of children with a central nervous system (CNS) tumour is improving. However, they experience late effects, including altered habits and patterns of sleep. We evaluated the presence and type of sleep disorders and daytime sleepiness in these children, and its associations with clinical characteristics and daily performance (fatigue and psychosocial functioning). In a cross-sectional study at the outpatient clinic of the Emma Children's Hospital AMC (February-June 2010), sleep, fatigue and psychosocial functioning were analysed in 31 CNS tumour patients (mean age: 11.8years; 20 boys) and compared with 78 patients treated for a non-CNS malignancy (mean age: 9.7years; 41 boys) and norm data. Questionnaires applied were the Sleep Disorder Scale for Children, the Epworth Sleepiness Scale, the Pediatric Quality of Life Inventory, and the Strengths and Difficulties Questionnaire. Sleeping habits and endocrine deficiencies were assessed with a self-developed questionnaire. Increased somnolence was found in CNS tumour patients compared with those with a non-CNS malignancy (8.8±2.8 versus 7.5±2.7; Psleep. No specific risk factors were identified for a sleep disorder in CNS tumour patients, but their excessive somnolence was correlated with lower fatigue related quality of life (QoL) (r=-0.78, Psleep quality and diminish fatigue. © 2011 European Sleep Research Society.

  2. Posterior leukoencephalopathy syndrome in poststretococcal acute glomerulonephritis

    International Nuclear Information System (INIS)

    Bazzino Borzone, F.; Pandolfo Arias, M.; Protasio Palomino, L.; Pujadas Ferrer, M.; Cerisola Cardozo, A.; Gonzalez, G.; Caggiani Malzone, M.; Rubio Santoro, I.

    2005-01-01

    Reversible posterior leukoencephalopathy (LEPR) is a clinical entity that affects radiation usually the white matter of the cerebral hemispheres. It is frequently associated with acute arterial hypertension and immunosuppressive therapy, among other causes. The clinical presentation is varied, with headache, nausea, vomiting, impaired consciousness and abnormal behavior, seizures and visual disturbances, symptoms that often regress. Computed tomography (CT) and magnetic resonance imaging (MRI) images show white matter edema predominantly in posterior regions of the brain. We present a 10 year old boy with leprosy in the course of a nephrotic syndrome secondary to acute diffuse glomerunefritis (GNDA) poststreptococcal. (author) [es

  3. Actuarial risk of isolated CNS involvement in Ewing's sarcoma following prophylactic cranial irradiation and intrathecal methotrexate

    International Nuclear Information System (INIS)

    Trigg, M.E.; Makuch, R.; Glaubiger, D.

    1985-01-01

    Records of 154 patients with Ewing's sarcoma treated at the National Cancer Institute were reviewed to assess the incidence and risk of developing isolated central nervous system (CNS) Ewing's sarcoma. Sixty-two of the 154 patients had received CNS irradiation and intrathecal (i.t.) methotrexate as part of their initial therapy to prevent the occurrence of isolated CNS Ewing's sarcoma. The risk of developing isolate CNS Ewing's sarcoma was greatest within the first two years after diagnosis and was approximately 10%. The overall risk of CNS recurrence in the group of patients receiving DNS treatment was similar to the group receiving no therapy directed to the CNS. The occurrence of isolated CNS involvement was not prevented by the use of CNS irradiation and i.t. methotrexate. Because of a lack of efficacy to the CNS irradiation regimen, current treatment regimens do not include therapy directed to CNS

  4. Savant Syndrome: Realities, Myths and Misconceptions

    Science.gov (United States)

    Treffert, Darold A.

    2014-01-01

    It was 126 years ago that Down first described savant syndrome as a specific condition and 70 years ago that Kanner first described Early Infantile Autism. While as many as one in ten autistic persons have savant abilities, such special skills occur in other CNS conditions as well such that approximately 50% of cases of savant syndrome have autism…

  5. Trigeminal Neuropathy in Sjogren′s Syndrome

    Directory of Open Access Journals (Sweden)

    Pinheiro L

    1999-01-01

    Full Text Available Trigeminal neuropathy is the most common CNS disorder in Sjogren′s syndrome. It is believed to be caused by vasculitis. Unless this is recognised, a diagnosis of trigeminal neuralgia is often made. The therapeutic response to steroids is unpredictable. There are two subgroups - those with associated collagen disorders and those only with the sicca syndrome.

  6. Nephrotic range proteinuria as a strong risk factor for rapid renal function decline during pre-dialysis phase in type 2 diabetic patients with severely impaired renal function.

    Science.gov (United States)

    Kitai, Yuichiro; Doi, Yohei; Osaki, Keisuke; Sugioka, Sayaka; Koshikawa, Masao; Sugawara, Akira

    2015-12-01

    Proteinuria is an established risk factor for progression of renal disease, including diabetic nephropathy. The predictive power of proteinuria, especially nephrotic range proteinuria, for progressive renal deterioration has been well demonstrated in diabetic patients with normal to relatively preserved renal function. However, little is known about the relationship between severity of proteinuria and renal outcome in pre-dialysis diabetic patients with severely impaired renal function. 125 incident dialysis patients with type 2 diabetes were identified. This study was aimed at retrospectively evaluating the impact of nephrotic range proteinuria (urinary protein-creatinine ratio above 3.5 g/gCr) on renal function decline during the 3 months just prior to dialysis initiation. In total, 103 patients (82.4 %) had nephrotic range proteinuria. The median rate of decline in estimated glomerular filtration rate (eGFR) in this study population was 0.98 (interquartile range 0.51-1.46) ml/min/1.73 m(2) per month. Compared to patients without nephrotic range proteinuria, patients with nephrotic range proteinuria showed significantly faster renal function decline (0.46 [0.24-1.25] versus 1.07 [0.64-1.54] ml/min/1.73 m(2) per month; p = 0.007). After adjusting for gender, age, systolic blood pressure, serum albumin, calcium-phosphorus product, hemoglobin A1c, and use of an angiotensin-converting enzyme inhibitor or an angiotensin II receptor blocker, patients with nephrotic range proteinuria showed a 3.89-fold (95 % CI 1.08-14.5) increased risk for rapid renal function decline defined as a decline in eGFR ≥0.5 ml/min/1.73 m(2) per month. Nephrotic range proteinuria is the predominant renal risk factor in type 2 diabetic patients with severely impaired renal function receiving pre-dialysis care.

  7. Bovine-associated CNS species resist phagocytosis differently

    Science.gov (United States)

    2013-01-01

    Background Coagulase-negative staphylococci (CNS) cause usually subclinical or mild clinical bovine mastitis, which often remains persistent. Symptoms are usually mild, mostly only comprising slight changes in the appearance of milk and possibly slight swelling. However, clinical mastitis with severe signs has also been reported. The reasons for the differences in clinical expression are largely unknown. Macrophages play an important role in the innate immunity of the udder. This study examined phagocytosis and killing by mouse macrophage cells of three CNS species: Staphylococcus chromogenes (15 isolates), Staphylococcus agnetis (6 isolates) and Staphylococcus simulans (15 isolates). Staphylococcus aureus (7 isolates) was also included as a control. Results All the studied CNS species were phagocytosed by macrophages, but S. simulans resisted phagocytosis more effectively than the other CNS species. Only S. chromogenes was substantially killed by macrophages. Significant variations between isolates were seen in both phagocytosis and killing by macrophages and were more common in the killing assays. Significant differences between single CNS species and S. aureus were observed in both assays. Conclusion This study demonstrated that differences in the phagocytosis and killing of mastitis-causing staphylococci by macrophages exist at both the species and isolate level. PMID:24207012

  8. Effects of prolonged treatment with memantine in the MRL model of CNS lupus.

    Science.gov (United States)

    Marcinko, Katarina; Parsons, Tiffany; Lerch, Jason P; Sled, John G; Sakic, Boris

    2012-09-01

    Neuropsychiatric manifestations and brain atrophy of unknown etiology are common and severe complications of systemic lupus erythematosus (SLE). An autoantibody that binds to N-methyl-D-aspartate (NMDA) receptor NR2 has been proposed as a key factor in the etiology of central nervous system (CNS) SLE. This hypothesis was supported by evidence suggesting memantine (MEM), an uncompetitive NMDA receptor antagonist, prevents behavioral dysfunction and brain pathology in healthy mice immunized with a peptide similar to an epitope on the NR2 receptor. Given that SLE is a chronic condition, we presently examine the effects of MEM in MRL/lpr mice, which develop behavioral deficits alongside SLE-like disease. A broad behavioral battery and 7-Tesla MRI were used to examine whether prolonged treatment with MEM (~25 mg/kg b.w. in drinking water) prevents CNS involvement in this spontaneous model of SLE. Although MEM increased novel object exploration in MRL/lpr mice, it did not show other beneficial, substrain-specific effects. Conversely, MEM was detrimental to spontaneous activity in control MRL +/+ mice and had a negative effect on body mass gain. Similarly, MRI revealed comparable increases in the volume of periventricular structures in MEM-treated groups. Sustained exposure to MEM affects body growth, brain morphology, and behavior primarily by pharmacological, and not autoimmunity-dependant mechanisms. Substrain-specific improvement in exploratory behavior of MEM-treated MRL/lpr mice may indicate that the NMDA system is merely a constituent of a complex pathogenenic cascade. However, it was evident that chronic administration of MEM is unable to completely prevent the development of a CNS SLE-like syndrome.

  9. Pericytes Stimulate Oligodendrocyte Progenitor Cell Differentiation during CNS Remyelination

    Directory of Open Access Journals (Sweden)

    Alerie Guzman De La Fuente

    2017-08-01

    Full Text Available The role of the neurovascular niche in CNS myelin regeneration is incompletely understood. Here, we show that, upon demyelination, CNS-resident pericytes (PCs proliferate, and parenchymal non-vessel-associated PC-like cells (PLCs rapidly develop. During remyelination, mature oligodendrocytes were found in close proximity to PCs. In Pdgfbret/ret mice, which have reduced PC numbers, oligodendrocyte progenitor cell (OPC differentiation was delayed, although remyelination proceeded to completion. PC-conditioned medium accelerated and enhanced OPC differentiation in vitro and increased the rate of remyelination in an ex vivo cerebellar slice model of demyelination. We identified Lama2 as a PC-derived factor that promotes OPC differentiation. Thus, the functional role of PCs is not restricted to vascular homeostasis but includes the modulation of adult CNS progenitor cells involved in regeneration.

  10. Can injured adult CNS axons regenerate by recapitulating development?

    Science.gov (United States)

    Hilton, Brett J; Bradke, Frank

    2017-10-01

    In the adult mammalian central nervous system (CNS), neurons typically fail to regenerate their axons after injury. During development, by contrast, neurons extend axons effectively. A variety of intracellular mechanisms mediate this difference, including changes in gene expression, the ability to form a growth cone, differences in mitochondrial function/axonal transport and the efficacy of synaptic transmission. In turn, these intracellular processes are linked to extracellular differences between the developing and adult CNS. During development, the extracellular environment directs axon growth and circuit formation. In adulthood, by contrast, extracellular factors, such as myelin and the extracellular matrix, restrict axon growth. Here, we discuss whether the reactivation of developmental processes can elicit axon regeneration in the injured CNS. © 2017. Published by The Company of Biologists Ltd.

  11. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs.

    Science.gov (United States)

    Sturm, Dominik; Orr, Brent A; Toprak, Umut H; Hovestadt, Volker; Jones, David T W; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J; Balasubramanian, Gnanaprakash; Worst, Barbara C; Pajtler, Kristian W; Brabetz, Sebastian; Johann, Pascal D; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M; Remke, Marc; Phillips, Joanna J; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C; Schniederjan, Matthew J; Santi, Mariarita; Buccoliero, Anna M; Dahiya, Sonika; Kramm, Christof M; von Bueren, André O; von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U; Shalaby, Tarek; Grotzer, Michael; van Meter, Timothy; Monoranu, Camelia-Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S; Taylor, Michael D; Jones, Chris; Jabado, Nada; Karajannis, Matthias A; Eils, Roland; Schlesner, Matthias; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M; Ellison, David W; Korshunov, Andrey; Kool, Marcel

    2016-02-25

    Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Phantom limb pain: a case of maladaptive CNS plasticity?

    DEFF Research Database (Denmark)

    Flor, Herta; Nikolajsen, Lone; Jensen, Troels Staehelin

    2006-01-01

    might be a phenomenon of the CNS that is related to plastic changes at several levels of the neuraxis and especially the cortex. Here, we discuss the evidence for putative pathophysiological mechanisms with an emphasis on central, and in particular cortical, changes. We cite both animal and human...

  13. Neurolymphomatosis: An International Primary CNS Lymphoma Collaborative Group report

    NARCIS (Netherlands)

    S. Grisariu (Sigal); B. Avni (Batia); T.T. Batchelor (Tracy); M.J. van den Bent (Martin); F. Bokstein (Felix); D. Schiff (David); O. Kuittinen (Outi); M.C. Chamberlain (Marc C.); P. Roth (Patrick); A. Nemets (Anatoly); E. Shalom (Edna); D. Ben-Yehuda (Dina); T. Siegal (Tali)

    2010-01-01

    textabstractNeurolymphomatosis (NL) is a rare clinical entity. The International Primary CNS Lymphoma Collaborative Group retrospectively analyzed 50 patients assembled from 12 centers in 5 countries over a 16-year period. NL was related to non-Hodgkin lymphoma in 90% and to acute leukemia in 10%.

  14. Causes of CNS inflammation and potential targets for anticonvulsants.

    Science.gov (United States)

    Falip, Mercé; Salas-Puig, Xavier; Cara, Carlos

    2013-08-01

    Inflammation is one of the most important endogenous defence mechanisms in an organism. It has been suggested that inflammation plays an important role in the pathophysiology of a number of human epilepsies and convulsive disorders, and there is clinical and experimental evidence to suggest that inflammatory processes within the CNS may either contribute to or be a consequence of epileptogenesis. This review discusses evidence from human studies on the role of inflammation in epilepsy and highlights potential new targets in the inflammatory cascade for antiepileptic drugs. A number of mechanisms have been shown to be involved in CNS inflammatory reactions. These include an inflammatory response at the level of the blood-brain barrier (BBB), immune-mediated damage to the CNS, stress-induced release of inflammatory mediators and direct neuronal dysfunction or damage as a result of inflammatory reactions. Mediators of inflammation in the CNS include interleukin (IL)-1β, tumour necrosis factor-α, nuclear factor-κB and toll-like receptor-4 (TLR4). IL-1β, BBB and high-mobility group box-1-TLR4 signalling appear to be the most promising targets for anticonvulsant agents directed at inflammation. Such agents may provide effective therapy for drug-resistant epilepsies in the future.

  15. Metallothionein Expression and Roles During Neuropathology in the CNS

    DEFF Research Database (Denmark)

    Penkowa, Milena

    2006-01-01

    , their receptors and neurotrophins (TGFb, TGFb-Receptor, bFGF, bFGF-Receptor, VEGF, NT-3, NT-4/5, NGF); angiogenesis; and growth cone formation. Hence, MT-I+II enhance CNS tissue repair as seen clearly after the cryogenic injury, after which MT-I+II promote substitution of the necrotic lesion cavity with a glial...

  16. Glypicans and FGFs in CNS Development and Function

    NARCIS (Netherlands)

    Galli, Antonella

    2003-01-01

    One of the most important events during central nervous system (CNS) development is the communication between cells. Cell-to-cell signaling implicates the interaction between a signaling molecules (or ligands) and their receptors. Ligand-receptor interaction is a tightly regulated process and is

  17. Sleep disorders in children after treatment for a CNS tumour

    NARCIS (Netherlands)

    Verberne, Lisa M.; Maurice-Stam, Heleen; Grootenhuis, Martha A.; van Santen, Hanneke M.; Schouten-van Meeteren, Antoinette Y. N.

    2012-01-01

    The long-term survival of children with a central nervous system (CNS) tumour is improving. However, they experience late effects, including altered habits and patterns of sleep. We evaluated the presence and type of sleep disorders and daytime sleepiness in these children, and its associations with

  18. PEG minocycline-liposomes ameliorate CNS autoimmune disease.

    Directory of Open Access Journals (Sweden)

    Wei Hu

    Full Text Available Minocycline is an oral tetracycline derivative with good bioavailability in the central nervous system (CNS. Minocycline, a potent inhibitor of matrix metalloproteinase (MMP-9, attenuates disease activity in experimental autoimmune encephalomyelitis (EAE, an animal model of multiple sclerosis (MS. Potential adverse effects associated with long-term daily minocycline therapy in human patients are concerning. Here, we investigated whether less frequent treatment with long-circulating polyethylene glycol (PEG minocycline liposomes are effective in treating EAE.Performing in vitro time kinetic studies of PEG minocycline-liposomes in human peripheral blood mononuclear cells (PBMCs, we determined that PEG minocycline-liposome preparations stabilized with CaCl(2 are effective in diminishing MMP-9 activity. Intravenous injections of PEG minocycline-liposomes every five days were as effective in ameliorating clinical EAE as daily intraperitoneal injections of minocycline. Treatment of animals with PEG minocycline-liposomes significantly reduced the number of CNS-infiltrating leukocytes, and the overall expression of MMP-9 in the CNS. There was also a significant suppression of MMP-9 expression and proteolytic activity in splenocytes of treated animals, but not in CNS-infiltrating leukocytes. Thus, leukocytes gaining access to the brain and spinal cord require the same absolute amount of MMP-9 in all treatment groups, but minocycline decreases the absolute cell number.Our data indicate that less frequent injections of PEG minocycline-liposomes are an effective alternative pharmacotherapy to daily minocycline injections for the treatment of CNS autoimmune diseases. Also, inhibition of MMP-9 remains a promising treatment target in EAE and patients with MS.

  19. [Non-structural abnormalities of CNS function resulting in coincidence of endocrinopathies, epilepsy and psychoneurologic disorders in children and adolescents].

    Science.gov (United States)

    Starzyk, Jerzy; Pituch-Noworolska, Anna; Pietrzyk, Jacek A; Urbanik, Andrzej; Kroczka, Sławomir; Drozdz, Ryszard; Wójcik, Małgorzata

    2010-01-01

    In the population of children and adolescents, epilepsy affects approximately 1% of cases, nonepileptic seizures are seen in approximately 3%, and endocrine disorders are several times more common. For this reason, coincidence of endocrine disorders and epilepsy and psychoneurologic disorders is frequent. Much less common are structural abnormalities (tumors, developmental abnormalities), and especially non-structural CNS abnormalities, resulting in coincidence of both disorders. There are no reports available in the literature that would address the problem. 1) Assessment of the frequency of coincidental epilepsy and endocrine disorders in patients without structural CSN abnormalities treated as outpatients and inpatients of Department of Endocrinology University Children's Hospital of Krakow. 2) Presentation of diagnostic and therapeutic difficulties in these patients, and 3) An attempt at defining the common etiology of both disorders. On the basis of ICD code patients with coincidance of endocrine disorders, epilepsy and psychoneurologic disorders were selected from several thousands of children treated between 2000 and 2009 in Pediatric Endocrinology Department. The neurologic disorders were diagnosed and treated in Chair and Department of Children's and Adolescents Neurology or in another pediatric neurology center. Various forms of epilepsy (symptomatic or idiopathic) and other psychoneurological disorders (disorders of behavior and emotions, obsession-compulsion syndromes, stereotypias, aggression, autoaggression, or hypothalamic obesity) coincident with one or more endocrine disorders, such as growth disorders, disorders of pubertal development, obesity, thyroid diseases, adrenal diseases, hyperprolactinemia, hypoparathyroidism and ion metabolism disorders were diagnosed in 49 patients. The group included: i) children after cranial irradiation and chemotherapy due to medulloblastoma (3 patients), oligodenroglioma (1 patient), ependymoma (1 patient), optic

  20. The shifting landscape of metastatic breast cancer to the CNS.

    Science.gov (United States)

    Quigley, Matthew R; Fukui, Olivia; Chew, Brandon; Bhatia, Sanjay; Karlovits, Steven

    2013-07-01

    The improved survival following the diagnosis of breast cancer has potentially altered the characteristics and course of patients presenting with CNS involvement. We therefore sought to define our current cohort of breast cancer patients with metastatic disease to the CNS in regard to modern biomarkers and clinical outcome. Review of clinical and radiographic records of women presenting to a tertiary medical center with the new diagnosis of CNS metastatic disease from breast cancer. This was a retrospective review from patients identities obtained from two prospective databases. There were 88 women analyzed who were treated over the period of January 2003 to February 2010, average age 56.9 years. At the time of initial presentation of CNS disease, 68 % of patients had multiple brain metastases, 17 % had a solitary metastasis, and 15 % had only leptomeningeal disease (LMD). The median survival for all patients from the time of diagnosis of breast disease was 50.0 months, and 9.7 months from diagnosis of CNS involvement. The only factor related to overall survival was estrogen receptor-positive pathology (57.6 v. 38.2 months, p = .02 log-rank); those related to survival post CNS diagnosis were presentation with LMD (p = .004, HR = 3.1, Cox regression) and triple-negative hormonal/HER2 status (p = .02, HR = 2.3, Cox regression). Patients with either had a median survival of 3.1 months (no patients in common). Of the 75 patients who initially presented with metastatic brain lesions, 20 (26 %) subsequently developed LMD in the course of their disease (median 10.4 months), following which survival was grim (1.8 months median). Symptoms of LMD were most commonly lower extremity weakness (14/33), followed by cranial nerve deficits (11/33). The recently described Graded Prognostic Assessment (GPA) tumor index stratified median survival at 2.5, 5.9, 13.1, and 21.7 months, respectively, for indices of 1-4 (p = .004, log-rank), which

  1. Prediction of human CNS pharmacokinetics using a physiologically-based pharmacokinetic modeling approach

    NARCIS (Netherlands)

    Yamamoto, Yumi; Valitalo, Pyry A.; Wong, Yin Cheong; Huntjens, Dymphy R.; Proost, Johannes H.; Vermeulen, An; Krauwinkel, Walter; Beukers, Margot W.; Kokki, Hannu; Kokki, Merja; Danhof, Meindert; van Hasselt, Johan G. C.; de Lange, Elizabeth C. M.

    2018-01-01

    Knowledge of drug concentration-time profiles at the central nervous system (CNS) target-site is critically important for rational development of CNS targeted drugs. Our aim was to translate a recently published comprehensive CNS physiologically-based pharmacokinetic (PBPK) model from rat to human,

  2. Tendencies the treatment of the central nervous system (CNS) tumors

    International Nuclear Information System (INIS)

    Alert Silva, Jose; Jimenez Medina, Jose

    2004-01-01

    It is known that the treatment of the central nervous system (CNS) tumors is based on the use of surgery and radiotherapy (RT) and that chemotherapy (QMT) is used even more, as well as the other drugs. A bibliographic review was made to update the knowledge on the current trends and perspectives of RT applied to CNS tumors. The following were found among them: a) combinations of RT and CMT; b) radiosensitizers incorporated to the radiant treatment; c) angiogenesis inhibitors associated with RT; d) the scale-up or increase of the RT doses thanks to the development of new technologies, such as 3 D conformal radiotherapy, intensity- modulated radiotherapy, surgery and others. Another field of research is that of the changes in the rhythm or fractioning of the RT: hyperfractionated, accelerated, combinations of both, etc., which will allow mainly to increase the dosage scale-up

  3. CNS-targets in control of energy and glucose homeostasis.

    Science.gov (United States)

    Kleinridders, André; Könner, A Christine; Brüning, Jens C

    2009-12-01

    The exceeding efforts in understanding the signals initiated by nutrients and hormones in the central nervous system (CNS) to regulate glucose and energy homeostasis have largely revolutionized our understanding of the neurocircuitry in control of peripheral metabolism. The ability of neurons to sense nutrients and hormones and to adopt a coordinated response to these signals is of crucial importance in controlling food intake, energy expenditure, glucose and lipid metabolism. Anatomical lesion experiments, pharmacological inhibition of signaling pathways, and, more recently, the analysis of conditional mouse mutants with modifications of hormone and nutrient signaling in defined neuronal populations have broadened our understanding of these complex neurocircuits. This review summarizes recent findings regarding the role of the CNS in sensing and transmitting nutritional and hormonal signals to control energy and glucose homeostasis and aims to define them as potential novel drug targets for the treatment of obesity and type 2 diabetes mellitus.

  4. 4th ENRI International Workshop on ATM/CNS

    CERN Document Server

    2017-01-01

    This book is a compilation of selected papers from the 4th ENRI International Workshop on ATM/CNS (EIWAC2015). The work focuses on novel techniques for aviation infrastructure in air traffic management (ATM) and communications, navigation, surveillance, and informatics (CNSI) domains. The contents make valuable contributions to academic researchers, engineers in the industry, and regulators of aviation authorities. As well, readers will encounter new ideas for realizing a more efficient and safer aviation system. .

  5. Morphological evaluation of fetus CNS and its related anomalies

    International Nuclear Information System (INIS)

    Oi, Shizuo; Tamaki, Norihiko; Matsumoto, Satoshi; Katayama, Kazuaki; Mochizuki, Matsuto

    1989-01-01

    The fetus central nervous system was evaluated morphologically by ultrasonography (US), magnetic resonance imaging (MRI), and CT scan to analyze the prenatal diagnostic value for CNS anomalies. A total of 31 patients with 42 lesions had been diagnosed during the preceding 7 years. The patients included 24 with hydrocephalus, three with anencephaly, three with myeloschisis, three with holoprosencephaly, three with an encephalocele, two with a Dandy-Walker cyst, one with hydroencephalodysplasia, one with an intracranial neoplasm, one with sacrococcygeal teratoma, and one with sacral agenesis. Compared with US and MRI, CT proved to be more accurate in the detection of spine and cranium-bone morphology. This finding seems to be valuable in the diagnosis of spina bifida, cranium bifidum and some cases of hypertensive hydrocephalus, especially in the axial view. MRI was definitely superior in the anatomico-pathological diagnosis of cerebral dysgenesis, ventriculomegaly, intracranial tumors, and other brain parenchymal changes in view of multi-dimensional analysis. The most considerable disadvantage of MRI in the diagnosis of a fetus CNS anomaly is the poor information about spine and cranium morphology. A super-conducting MRI system is still insufficient to demonstrate the spinal cord of a fetus. US was routinely used, and the multidimensional slices were useful for screening the CNS abnormalies. Some of the fetus brain lesions, such as intracranial hematomas, had a specific echogenecity on US. However, US sometimes failed to demarcate the cerebral parenchymal or subdural morphological changes because its artifacts had hyperchoic shadows. While US, MRI, and CT were valuable diagnostic tools in the morphological evaluation of fetus CNS and its related anomalies, each modality has different diagnostic advantages and disadvantages. Improvement can be expected when these diagnostic imaging modalities are complementary, depending upon the nature of the anatomy. (J.P.N.)

  6. Primary CNS lymphoma in nonimmunocompromised patients magnetic resonance study

    International Nuclear Information System (INIS)

    Pena, J.; Fernandez, J.M.; Galarraga, M.I.; Pozo, A.; Montes, A.; Ablanedo, P.

    1995-01-01

    Prymary lymphoma of the CNS (PLCNS) is a relatively infrequent malignant tumor that has become increasingly common over the past decade. The radiological signs, although not pathognomonic, are quite specific and suggestive of the correct diagnosis, thus facilitating therapeutic management. We present six cases of PLCNS in nonimmunocopromised patients studied by MR in our hospital over the past two and a half years. We describe theradiological findings, correlating them with those mentioned in the literature. 14 refs

  7. Melanocortin signaling in the CNS directly regulates circulating cholesterol

    OpenAIRE

    Perez-Tilve, Diego; Hofmann, Susanna M; Basford, Joshua; Nogueiras, Ruben; Pfluger, Paul T; Patterson, James T; Grant, Erin; Wilson-Perez, Hilary E; Granholm, Norman A; Arnold, Myrtha; Trevaskis, James L; Butler, Andrew A; Davidson, William S; Woods, Stephen C; Benoit, Stephen C

    2010-01-01

    Cholesterol circulates in the blood in association with triglycerides and other lipids, and elevated blood low-density lipoprotein cholesterol carries a risk for metabolic and cardiovascular disorders, whereas high-density lipoprotein (HDL) cholesterol in the blood is thought to be beneficial. Circulating cholesterol is the balance among dietary cholesterol absorption, hepatic synthesis and secretion, and the metabolism of lipoproteins by various tissues. We found that the CNS is also an impo...

  8. Computerized tomography data on CNS affection in systemic lupus erythematosus

    International Nuclear Information System (INIS)

    Ivanova, M.M.; Bliznyuk, O.I.; Todua, F.I.; Tumanova, A.A.

    1989-01-01

    Computed tomography (CT) of the brain was employed in 40 patients with systemic lupus erythematosus (SLE). Clinical cerebral pathology was obvious in 30 and absent in 10 patients. By CT cerebral symptoms were divided of 4 groups. Clinical symptom complexes of CNS defects and SLE were reflected on definite CT images correlated with focal damage to the brain. CT picture of enlarged subarachnoid space, ventricles and basal cisterns can be observed in SLE patients without neurological symptoms. This indicated likely subclinical cerebral affection

  9. EMMPRIN, an upstream regulator of MMPs, in CNS biology.

    Science.gov (United States)

    Kaushik, Deepak Kumar; Hahn, Jennifer Nancy; Yong, V Wee

    2015-01-01

    Matrix metalloproteinases (MMPs) are engaged in pathologies associated with infections, tumors, autoimmune disorders and neurological dysfunctions. With the identification of an upstream regulator of MMPs, EMMPRIN (Extracellular matrix metalloproteinase inducer, CD147), it is relevant to address if EMMPRIN plays a role in the pathology of central nervous system (CNS) diseases. This would enable the possibility of a more upstream and effective therapeutic target. Indeed, conditions including gliomas, Alzheimer's disease (AD), multiple sclerosis (MS), and other insults such as hypoxia/ischemia show elevated levels of EMMPRIN which correlate with MMP production. In contrast, given EMMPRIN's role in CNS homeostasis with respect to regulation of monocarboxylate transporters (MCTs) and interactions with adhesion molecules including integrins, we need to consider that EMMPRIN may also serve important regulatory or protective functions. This review summarizes the current understanding of EMMPRIN's involvement in CNS homeostasis, its possible roles in escalating or reducing neural injury, and the mechanisms of EMMPRIN including and apart from MMP induction. Copyright © 2015 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  10. Mechanisms of CNS invasion and damage by parasites.

    Science.gov (United States)

    Kristensson, Krister; Masocha, Willias; Bentivoglio, Marina

    2013-01-01

    Invasion of the central nervous system (CNS) is a most devastating complication of a parasitic infection. Several physical and immunological barriers provide obstacles to such an invasion. In this broad overview focus is given to the physical barriers to neuroinvasion of parasites provided at the portal of entry of the parasites, i.e., the skin and epithelial cells of the gastrointestinal tract, and between the blood and the brain parenchyma, i.e., the blood-brain barrier (BBB). A description is given on how human pathogenic parasites can reach the CNS via the bloodstream either as free-living or extracellular parasites, by embolization of eggs, or within red or white blood cells when adapted to intracellular life. Molecular mechanisms are discussed by which parasites can interact with or pass across the BBB. The possible targeting of the circumventricular organs by parasites, as well as the parasites' direct entry to the brain from the nasal cavity through the olfactory nerve pathway, is also highlighted. Finally, examples are given which illustrate different mechanisms by which parasites can cause dysfunction or damage in the CNS related to toxic effects of parasite-derived molecules or to immune responses to the infection. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. CNS Involvement in Hemophagocytic Lymphohistiocytosis: CT and MR Findings

    International Nuclear Information System (INIS)

    Chung, Tae Woong

    2007-01-01

    Hemophagocytic lymphohistiocytosis (HLH) is a rare disorder that is characterized by proliferation of benign histiocytes, and this commonly involves the liver, spleen, lymph nodes, bone marrow and central nervous system (CNS). We report here on the CT and MR imaging findings in a case of CNS HLH that showed multiple ring enhancing masses mimicking abscess or another mass on the CT and MR imaging. emophagocytic lymphohistiocytosis (HLH) is a rare disorder that is characterized by nonmalignant diffuse infiltration of multiple organs, including the central nervous system (CNS), by lymphocytes and histiocytes (1). Many radiologic reports describing diffuse white matter infiltrations, parenchymal atrophy and calcification have been published, but the characteristics of these findings remain non-specific, especially in immunocompromised patients. We present here a case of HLH in a 3-year-old boy who presented with multiple ring enhancing lesions involving the brain. In conclusion, although the CT and MRI findings of HLH with ring enhancing parenchymal lesions are nonspecific and mimic abscess, and especially in the immunosuppressed patients, increased diffusion at the center on DWI may be a finding of HLH to differentiate it from abscess, which has restricted diffusion at the center. However, the pathologic correlation with DWI according to the lesion stage certainly needs further study with a larger number of patients

  12. Adverse CNS-effects of beta-adrenoceptor blockers.

    Science.gov (United States)

    Gleiter, C H; Deckert, J

    1996-11-01

    In 1962 propranolol, the first beta adrenoceptor antagonist (beta blocker), was brought on to the market. There is now a host of different beta blockers available, and these compounds are among the most commonly prescribed groups of drugs. The efficacy of beta blockers has been proven predominantly for the treatment of cardiovascular diseases. Beta blockers are also used for certain types of CNS disorders, such as anxiety disorders, essential tremor and migraine. While low toxicity means that they have a favorable risk-benefit ratio, given the high intensity of use, it is essential to have a comprehensive knowledge of adverse events. Adverse events of beta blockers that can be related to the CNS are quite often neglected, even in textbooks of clinical pharmacology or review articles, and thus often misdiagnosed. The following article, therefore, after summarizing the use of beta blockers for CNS indications, critically reviews the literature on centrally mediated adverse events. General pharmacological features of beta blockers and their molecular basis of action will briefly be addressed to the extent that they are or may become relevant for central nervous pharmacotherapy and side-effects.

  13. Microtubule-Targeting Agents Enter the Central Nervous System (CNS): Double-edged Swords for Treating CNS Injury and Disease.

    Science.gov (United States)

    Hur, Eun-Mi; Lee, Byoung Dae

    2014-12-01

    Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs) are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS) are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

  14. Microtubule-Targeting Agents Enter the Central Nervous System (CNS: Double-edged Swords for Treating CNS Injury and Disease

    Directory of Open Access Journals (Sweden)

    Eun-Mi Hur

    2014-12-01

    Full Text Available Microtubules have been among the most successful targets in anticancer therapy and a large number of microtubule-targeting agents (MTAs are in various stages of clinical development for the treatment of several malignancies. Given that injury and diseases in the central nervous system (CNS are accompanied by acute or chronic disruption of the structural integrity of neurons and that microtubules provide structural support for the nervous system at cellular and intracellular levels, microtubules are emerging as potential therapeutic targets for treating CNS disorders. It has been postulated that exogenous application of MTAs might prevent the breakdown or degradation of microtubules after injury or during neurodegeneration, which will thereby aid in preserving the structural integrity and function of the nervous system. Here we review recent evidence that supports this notion and also discuss potential risks of targeting microtubules as a therapy for treating nerve injury and neurodegenerative diseases.

  15. Adiponectin Suppresses T Helper 17 Cell Differentiation and Limits Autoimmune CNS Inflammation via the SIRT1/PPARγ/RORγt Pathway.

    Science.gov (United States)

    Zhang, Kai; Guo, Yawei; Ge, Zhenzhen; Zhang, Zhihui; Da, Yurong; Li, Wen; Zhang, Zimu; Xue, Zhenyi; Li, Yan; Ren, Yinghui; Jia, Long; Chan, Koon-Ho; Yang, Fengrui; Yan, Jun; Yao, Zhi; Xu, Aimin; Zhang, Rongxin

    2017-09-01

    T helper 17 (Th17) cells are vital components of the adaptive immune system involved in the pathogenesis of most autoimmune and inflammatory syndromes, and adiponectin(ADN) is correlated with inflammatory diseases such as multiple sclerosis (MS) and type II diabetes. However, the regulatory effects of adiponectin on pathogenic Th17 cell and Th17-mediated autoimmune central nervous system (CNS) inflammation are not fully understood. In this study, we demonstrated that ADN could inhibit Th1 and Th17 but not Th2 cells differentiation in vitro. In the in vivo study, we demonstrated that ADN deficiency promoted CNS inflammation and demyelination and exacerbated experimental autoimmune encephalomyelitis (EAE), an animal model of human MS. Furthermore, ADN deficiency increased the Th1 and Th17 cell cytokines of both the peripheral immune system and CNS in mice suffering from EAE. It is worth mentioning that ADN deficiency predominantly promoted the antigen-specific Th17 cells response in autoimmune encephalomyelitis. In addition, in vitro and in vivo, ADN upregulated sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor γ (PPARγ) and inhibited retinoid-related orphan receptor-γt (RORγt); the key transcription factor during Th17 cell differentiation. These results systematically uncovered the role and mechanism of adiponectin on pathogenic Th17 cells and suggested that adiponectin could inhibit Th17 cell-mediated autoimmune CNS inflammation.

  16. Arthropathy and proteinuria: nail-patella syndrome revisited

    Directory of Open Access Journals (Sweden)

    Albishri, Jamal

    2014-11-01

    Full Text Available [english] Nail-patella syndrome (NPS is a pleiotropic autosomal-dominant disorder due to mutations in the gene LMX1B. It has traditionally been characterized by a tetrad of dermatologic and musculoskeletal abnormalities. However, one of the most serious manifestations of NPS is kidney disease, which may be present in up to 40% of affected individuals. Although diagnosis can be made at birth, it is often missed, presumably due to the rarity of the condition. A 35-year-old female presented to our clinic with history of small joint pain of 6 months duration. In addition she complained of pedal edema off and on for the last 12 years. Prior to her current presentation she had been managed by a local doctor symptomatically. On evaluation, a nephrotic syndrome was obvious, but no secondary cause could be found. However, her physical examination was characteristic of NPS and keeping in view the autosomal dominant nature of the disorder all her three siblings were screened who too showed classical features of NPS. This rare syndrome as a cause of nephrotic range proteinuria is discussed in this report. The report underlines the importance of a good physical examination in a given clinical setting.

  17. Endovascular transplantation of stem cells to the injured rat CNS

    International Nuclear Information System (INIS)

    Lundberg, Johan; Soederman, Mikael; Andersson, Tommy; Holmin, Staffan; Le Blanc, Katarina

    2009-01-01

    Transplantation procedures using intraparenchymal injection of stem cells result in tissue injury in addition to associated surgical risks. Intravenous injection of mesenchymal stem cells gives engraftment to lesions, but the method has low efficiency and specificity. In traumatic brain injuries (TBI), there is a transient breakdown of the blood-brain barrier and an inflammatory response, which increase migration of cells from blood to parenchyma. The aim of this investigation was to analyze the effect of intra-arterial administration on cellular engraftment. Experimental TBI was produced in a rat model. Endovascular technique was used to administer human mesenchymal stem cells in the ipsilateral internal carotid artery. Evaluation of engraftment and side effects were performed by immunohistochemical analysis of the brain and several other organs. The results were compared to intravenous administration of stem cells. Intra-arterial transplantion of mesenchymal stem cells resulted in central nervous system (CNS) engraftment without thromboembolic ischemia. We observed a significantly higher number of transplanted cells in the injured hemisphere after intra-arterial compared to intravenous administration both 1 day (p<0.01) and 5 days (p<0.05) after the transplantation. Some cells were also detected in the spleen but not in the other organs analyzed. Selective intra-arterial administration of mesenchymal stem cells to the injured CNS is a minimally invasive method for transplantation. The method is significantly more efficient than the intravenous route and causes no side effects in the current model. The technique can potentially be used for repeated transplantation to the CNS after TBI and in other diseases. (orig.)

  18. Endovascular transplantation of stem cells to the injured rat CNS

    Energy Technology Data Exchange (ETDEWEB)

    Lundberg, Johan; Soederman, Mikael; Andersson, Tommy; Holmin, Staffan [Karolinska University Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Department of Neuroradiology, Stockholm (Sweden); Le Blanc, Katarina [Karolinska University Hospital, Department of Stem Cell Research, Karolinska Institutet, Department of Clinical Immunology, Stockholm (Sweden)

    2009-10-15

    Transplantation procedures using intraparenchymal injection of stem cells result in tissue injury in addition to associated surgical risks. Intravenous injection of mesenchymal stem cells gives engraftment to lesions, but the method has low efficiency and specificity. In traumatic brain injuries (TBI), there is a transient breakdown of the blood-brain barrier and an inflammatory response, which increase migration of cells from blood to parenchyma. The aim of this investigation was to analyze the effect of intra-arterial administration on cellular engraftment. Experimental TBI was produced in a rat model. Endovascular technique was used to administer human mesenchymal stem cells in the ipsilateral internal carotid artery. Evaluation of engraftment and side effects were performed by immunohistochemical analysis of the brain and several other organs. The results were compared to intravenous administration of stem cells. Intra-arterial transplantion of mesenchymal stem cells resulted in central nervous system (CNS) engraftment without thromboembolic ischemia. We observed a significantly higher number of transplanted cells in the injured hemisphere after intra-arterial compared to intravenous administration both 1 day (p<0.01) and 5 days (p<0.05) after the transplantation. Some cells were also detected in the spleen but not in the other organs analyzed. Selective intra-arterial administration of mesenchymal stem cells to the injured CNS is a minimally invasive method for transplantation. The method is significantly more efficient than the intravenous route and causes no side effects in the current model. The technique can potentially be used for repeated transplantation to the CNS after TBI and in other diseases. (orig.)

  19. Immune and inflammatory responses in the CNS : Modulation by astrocytes

    DEFF Research Database (Denmark)

    Penkowa, Milena; aschner, michael; hidalgo, juan

    2008-01-01

    Beyond their long-recognized support functions, astrocytes are active partners of neurons in processing information, synaptic integration, and production of trophic factors, just to name a few. Both microglia and astrocytes produce and secrete a number of cytokines, modulating and integrating...... the communication between hematogenous cells and resident cells of the central nervous system (CNS). This review will address (1) the functions of astrocytes in the normal brain and (2) their role in surveying noxious stimuli within the brain, with particular emphasis on astrocytic responses to damage or disease...

  20. Kynurenines in CNS disease: regulation by inflammatory cytokines

    Science.gov (United States)

    Campbell, Brian M.; Charych, Erik; Lee, Anna W.; Möller, Thomas

    2014-01-01

    The kynurenine pathway (KP) metabolizes the essential amino acid tryptophan and generates a number of neuroactive metabolites collectively called the kynurenines. Segregated into at least two distinct branches, often termed the “neurotoxic” and “neuroprotective” arms of the KP, they are regulated by the two enzymes kynurenine 3-monooxygenase and kynurenine aminotransferase, respectively. Interestingly, several enzymes in the pathway are under tight control of inflammatory mediators. Recent years have seen a tremendous increase in our understanding of neuroinflammation in CNS disease. This review will focus on the regulation of the KP by inflammatory mediators as it pertains to neurodegenerative and psychiatric disorders. PMID:24567701

  1. CNS penetration of intrathecal-lumbar idursulfase in the monkey, dog and mouse: implications for neurological outcomes of lysosomal storage disorder.

    Directory of Open Access Journals (Sweden)

    Pericles Calias

    Full Text Available A major challenge for the treatment of many central nervous system (CNS disorders is the lack of convenient and effective methods for delivering biological agents to the brain. Mucopolysaccharidosis II (Hunter syndrome is a rare inherited lysosomal storage disorder resulting from a deficiency of iduronate-2-sulfatase (I2S. I2S is a large, highly glycosylated enzyme. Intravenous administration is not likely to be an effective therapy for disease-related neurological outcomes that require enzyme access to the brain cells, in particular neurons and oligodendrocytes. We demonstrate that intracerebroventricular and lumbar intrathecal administration of recombinant I2S in dogs and nonhuman primates resulted in widespread enzyme distribution in the brain parenchyma, including remarkable deposition in the lysosomes of both neurons and oligodendrocytes. Lumbar intrathecal administration also resulted in enzyme delivery to the spinal cord, whereas little enzyme was detected there after intraventricular administration. Mucopolysaccharidosis II model is available in mice. Lumbar administration of recombinant I2S to enzyme deficient animals reduced the storage of glycosaminoglycans in both superficial and deep brain tissues, with concurrent morphological improvements. The observed patterns of enzyme transport from cerebrospinal fluid to the CNS tissues and the resultant biological activity (a warrant further investigation of intrathecal delivery of I2S via lumbar catheter as an experimental treatment for the neurological symptoms of Hunter syndrome and (b may have broader implications for CNS treatment with biopharmaceuticals.

  2. Periodic fever: From Still's disease to Muckle-Wells syndrome.

    Science.gov (United States)

    Solís Marquínez, Marta Nataya; García Fernández, Edilia; Morís de la Tassa, Joaquín

    2017-06-02

    Muckle-Wells syndrome is a systemic autoinflammatory disease included in the group of hereditary periodic febrile syndromes. We report the case of a patient with this rare disease to call the attention to the singularity of this condition, its low incidence, its atypical presentation and the subsequent delay in the diagnosis, which is reached when late and devastating consequences have taken place. In this case, the first-line therapy, anti-interleukin 1 (IL-1), failed to control the disease. Nevertheless, the IL-6 inhibitor, tocilizumab, proved effective, achieving the total remission of nephrotic syndrome associated with AA secondary amyloidosis, changing the bleak prognosis of this disease. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  3. Neurotransmitter synthesis from CNS glutamine for central control of breathing

    International Nuclear Information System (INIS)

    Hoop, B.; Systrom, D.; Chiang, C.H.; Shih, V.E.; Kazemi, H.

    1986-01-01

    The maximum rate at which CNS glutamine (GLN) derived from glutamate (GLU) can be sequestered for synthesis of neurotransmitter GLU and/or γ-aminobutyric acid (GABA) has been determined in pentobarbital-anesthetized dogs. A total of 57 animals were studied under normal, hypoxic (Pa/sub O2/ greater than or equal to 20 mmHg), or hypercapnic (Pa/sub CO2/ less than or equal to 71 mm Hg) conditions. Thirteen of these were bilaterally vagotomized and carotid body denervated and studied only under normoxic or hypoxic conditions. In 5 animals cerebrospinal fluid GLN transfer rate constant k was measured using 13 N-ammonia tracer. Measured cerebral cortical (CC) and medullary (MED) GLN concentrations c are found to vary with GLU metabolic rate r according to c-C/sub m/r/(r+R), where r, the product of k and corresponding tissue GLU concentration, is assumed equal to the maximum GLN metabolic rate via pathways other than for neurotransmitter synthesis. The constants C/sub m/ and R are the predicted maximum GLN concentration and its maximum rate of sequestration for neurotransmitter synthesis, respectively. For both CNS tissue types in all animals, C/sub m/ = 20.9 +- 7.4 (SD) mmoles/kg wet wt(mM) and R = 6.2 +- 2.3 mM/min. These values are consistent with results obtained in anesthetized rats

  4. Glibenclamide for the Treatment of Acute CNS Injury

    Directory of Open Access Journals (Sweden)

    J. Marc Simard

    2013-10-01

    Full Text Available First introduced into clinical practice in 1969, glibenclamide (US adopted name, glyburide is known best for its use in the treatment of diabetes mellitus type 2, where it is used to promote the release of insulin by blocking pancreatic KATP [sulfonylurea receptor 1 (Sur1-Kir6.2] channels. During the last decade, glibenclamide has received renewed attention due to its pleiotropic protective effects in acute CNS injury. Acting via inhibition of the recently characterized Sur1-Trpm4 channel (formerly, the Sur1-regulated NCCa-ATP channel and, in some cases, via brain KATP channels, glibenclamide has been shown to be beneficial in several clinically relevant rodent models of ischemic and hemorrhagic stroke, traumatic brain injury, spinal cord injury, neonatal encephalopathy of prematurity, and metastatic brain tumor. Glibenclamide acts on microvessels to reduce edema formation and secondary hemorrhage, it inhibits necrotic cell death, it exerts potent anti-inflammatory effects and it promotes neurogenesis—all via inhibition of Sur1. Two clinical trials, one in TBI and one in stroke, currently are underway. These recent findings, which implicate Sur1 in a number of acute pathological conditions involving the CNS, present new opportunities to use glibenclamide, a well-known, safe pharmaceutical agent, for medical conditions that heretofore had few or no treatment options.

  5. Activity-Driven CNS Changes in Learning and Development

    Science.gov (United States)

    1991-04-14

    with Korsakoffs syndrome and exhibiting severe amnesia was shown to have normal levels of eyeblink conditioning even though he had no recollection of...34isolation syndrome " of the sort described by Harlow et al.59 and others, which appears to be relatively unique to, or most pronounced in, the rhesus monkey

  6. Nuclear innovation through collaboration. 35th Annual CNS conference and 39th CNS/CNA student conference

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2015-07-01

    The Canadian Nuclear Society (CNS) held its 35th Annual Conference in Saint John, New Brunswick, Canada on May 31 to June 3, 2015, combined with the 39th Annual CNS/CNA Student Conference. With the theme of the conference, 'Nuclear Innovation through Collaboration', more than 425 delegates, exhibitors and students were in attendance. The conference commenced with two strong plenary sessions on Utility Collaborations to Improve Lifetime Performance; and, Performance Improvement Programs: Goals and Experience. The second day consisted of the panel discussions on International Developments in Used Nuclear Fuel Repository Programs, and two plenary sessions on: Enterprise Risk Management; and, Vendor Role in a Continuously Improving Industry. The third day contained a number of interesting features, including plenary sessions on Waste Management and Decommissioning; Developing Technologies and Resources, and a panel discussion on the Transportation of Used Nuclear Fuel. All three days of the conference also contained parallel sessions with over 100 technical papers presented at the main and student sessions. The technical session titles were: Refurbishment and Life Extension; Thermalhydraulics; Nuclear Materials; WMD - Radiation Monitoring; Safety and Licensing; Communication; Safety and Licensing; Instrumentation and Control; Advanced Reactor Designs; WMD - Deep Geological Repository Packaging; Reactor Physics; Chemistry and Materials; Advanced Fuel Cycles; Waste Management and Decommissioning; and, Medical Physics and Radiation Biology.

  7. Nuclear innovation through collaboration. 35th Annual CNS conference and 39th CNS/CNA student conference

    International Nuclear Information System (INIS)

    2015-01-01

    The Canadian Nuclear Society (CNS) held its 35th Annual Conference in Saint John, New Brunswick, Canada on May 31 to June 3, 2015, combined with the 39th Annual CNS/CNA Student Conference. With the theme of the conference, 'Nuclear Innovation through Collaboration', more than 425 delegates, exhibitors and students were in attendance. The conference commenced with two strong plenary sessions on Utility Collaborations to Improve Lifetime Performance; and, Performance Improvement Programs: Goals and Experience. The second day consisted of the panel discussions on International Developments in Used Nuclear Fuel Repository Programs, and two plenary sessions on: Enterprise Risk Management; and, Vendor Role in a Continuously Improving Industry. The third day contained a number of interesting features, including plenary sessions on Waste Management and Decommissioning; Developing Technologies and Resources, and a panel discussion on the Transportation of Used Nuclear Fuel. All three days of the conference also contained parallel sessions with over 100 technical papers presented at the main and student sessions. The technical session titles were: Refurbishment and Life Extension; Thermalhydraulics; Nuclear Materials; WMD - Radiation Monitoring; Safety and Licensing; Communication; Safety and Licensing; Instrumentation and Control; Advanced Reactor Designs; WMD - Deep Geological Repository Packaging; Reactor Physics; Chemistry and Materials; Advanced Fuel Cycles; Waste Management and Decommissioning; and, Medical Physics and Radiation Biology.

  8. Differential expression of metallothioneins in the CNS of mice with experimental autoimmune encephalomyelitis

    DEFF Research Database (Denmark)

    Espejo, C; Carrasco, J; Hidalgo, J

    2001-01-01

    Multiple sclerosis is an inflammatory, demyelinating disease of the CNS. Metallothioneins-I+II are antioxidant proteins induced in the CNS by immobilisation stress, trauma or degenerative diseases which have been postulated to play a neuroprotective role, while the CNS isoform metallothionein......-III has been related to Alzheimer's disease. We have analysed metallothioneins-I-III expression in the CNS of mice with experimental autoimmune encephalomyelitis. Moreover, we have examined the putative role of interferon-gamma, a pro-inflammatory cytokine, in the control of metallothioneins expression...

  9. Imaging Findings of Central Nervous System Vasculitis Associated with Goodpasture's Syndrome: a Case Report

    International Nuclear Information System (INIS)

    Kim, Jee Young; Ahn, Kook Jin; Jung, Jung Im; Jung, So Lyung; Kim, Bum Soo; Hahn, Seong Tae

    2007-01-01

    We report a rare case of CNS vasculitis associated with Goodpasture's syndrome in a 34-year-old man, who presented with a seizure and sudden onset of right sided weakness. He also had recurrent hemoptysis of one month's duration. Goodpasture's syndrome is histologically diagnosed by intense linear deposits of IgG along the glomerular basement membrane in both renal and lung tissues. oodpasture's syndrome is a rare disease, characterized by rapidly progressive glomerulonephritis, diffuse pulmonary hemorrhage and circulating antiglomerular basement membrane antibody (anti-GBM antibody). Central nervous system (CNS) manifestations in Goodpasture's syndrome are extremely rare, with only a few cases having been reported in the literature (8 10). Therefore, we present our imaging findings of CNS vasculitis associated with Goodpasture's syndrome, together with a review of the relevant literature. In summary, CNS vasculitis associated with Goodpasture's syndrome is extremely rare. Awareness of the imaging findings, as well as the clinical significance of CNS vasculitis associated with Goodpasture's syndrome, can be helpful in making the correct diagnosis and subsequent management of this rare condition

  10. 6. CNS international conference on CANDU maintenance. Proceedings

    International Nuclear Information System (INIS)

    2003-01-01

    The 6th CNS International Conference on CANDU Maintenance took place in Toronto, Ontario on November 16-18, 2003. The theme for the conference was 'Maintenance for Life'. About 270 delegates attended the conference held by the Canadian Nuclear Society. The conference consisted of four parallel sessions, a pattern that continued throughout the conference. Papers were grouped under the following headings: Fuel Channels and End Fittings - Assessments; Fuel Channels and End Fittings - Inspections; Fuel Channels and End Fittings - Maintenance; Fuel Channels and End Fittings - Universal Delivery Machine; Water Upgrading; Performance and Plant Life Improvement; Steam Generator Life Management; Steam Generator Modifications; Steam Generators - Inspections; Steam Generators - Assessments; Maintenance Programs; Feeder Inspections; Feeder Assessment and Mitigation; Valve Maintenance; Instrumentation and Control; Inspection Technology; and Fuel Handling

  11. Resveratrol Neuroprotection in Stroke and Traumatic CNS injury

    Science.gov (United States)

    Lopez, Mary; Dempsey, Robert J; Vemuganti, Raghu

    2015-01-01

    Resveratrol, a stilbene formed in many plants in response to various stressors, elicits multiple beneficial effects in vertebrates. Particularly, resveratrol was shown to have therapeutic properties in cancer, atherosclerosis and neurodegeneration. Resveratrol-induced benefits are modulated by multiple synergistic pathways that control oxidative stress, inflammation and cell death. Despite the lack of a definitive mechanism, both in vivo and in vitro studies suggest that resveratrol can induce a neuroprotective state when administered acutely or prior to experimental injury to the CNS. In this review, we discuss the neuroprotective potential of resveratrol in stroke, traumatic brain injury and spinal cord injury, with a focus on the molecular pathways responsible for this protection. PMID:26277384

  12. Brain abscess with an unexpected finding: Actinomyces meyeri CNS infection

    DEFF Research Database (Denmark)

    Eiset, Andreas Halgreen; Thomsen, Marianne Kragh; Wejse, Christian

    -up. The source of infection was most likely periodontitis with spread to the lungs from aspiration or oropharyngeal secretion into the respiratory tract, alternatively from haematogenous spread. Conclusions: We report of the successful treatment of a cerebral abscess caused by A. meyeri with narrow spectrum......Background: CNS infection caused by Actinomyces spp. is rare and the subtype Actinomyces meyeri even rarer. Risk factors include periodontal disease and alcohol overuse. We present a case report of a 54-year-old female with dental and lung foci. Case history: A female was hospitalised with tonic...... oedema. By MRI an abscess was suspected and the patient was transferred to the department of neurosurgery, where drainage was performed. Microscopy revealed gram-positive cocci and gram-negative rods and iv. treatment with ceftriaxone 4g x 1 and metronidazole 1g x 1 was commenced. Pus cultures showed...

  13. Gene therapy for CNS diseases – Krabbe disease

    Directory of Open Access Journals (Sweden)

    Mohammad A. Rafi

    2016-06-01

    Full Text Available This is a brief report of the 19th Annual Meeting of the American Society of Gene and Cell Therapy that took place from May 4th through May 7th, 2016 in Washington, DC, USA. While the meeting provided many symposiums, lectures, and scientific sessions this report mainly focuses on one of the sessions on the "Gene Therapy for central nervous system (CNS Diseases" and specifically on the "Gene Therapy for the globoid cell leukodystrophy or Krabbe disease. Two presentations focused on this subject utilizing two animal models of this disease: mice and dog models. Different serotypes of adeno-associate viral vectors (AAV alone or in combination with bone marrow transplantations were used in these research projects. The Meeting of the ASGCT reflected continuous growth in the fields of gene and cell therapy and brighter forecast for efficient treatment options for variety of human diseases.

  14. Radioprotection of mouse CNS endothelial cells in vivo

    International Nuclear Information System (INIS)

    Lyubimova, N.; Coultas, P.; Martin, R.

    1996-01-01

    Full text: Radioprotection using the minor groove binding DNA ligand Hoechst 33342 has been demonstrated in vitro, and more recently in vivo, in mouse lung. Intravenous administration was used for the lung studies, and both endothelial and alveolar epithelial cells-showed good up-take. Radiation damage to the endothelial cell population has also been postulated as important in late developing radionecrosis of spinal cord and brain. Endothelial cell density in brain can be readily determined by a fluorescent-histochemical technique. Treatment with a monoamine oxidase inhibitor and subsequent injection with L-DOPA results in an accumulation of dopamine (DA) in CNS endothelial cells. DA is converted to a fluorophore by exposure to paraformaldehyde, and cell numbers assayed by fluorescence microscopy. Earlier studies used this technique to monitor post-irradiation changes in endothelial cell density in rodent brain and showed the loss, within 24 hours, of a sensitive subpopulation comprising about 15% of the endothelial cells. Ten minutes after intravenous injection of Hoechst 33342 (80mg/kg) the ligand is confined by its limited penetration to the endothelial cells in mouse brain. When we irradiated at this time, there was protection against early endothelial cell loss. Ablation of the sensitive subpopulation in unprotected mice takes place over a dose range of 1 to 3 Gy γ-rays, but doses between 12 to 20 Gy are required in the presence of ligand. This protection equates to a very high dose modification factor of about 7 and possibly reflects a suppression of apoptosis in the sensitive endothelial subpopulation. The extent to which there is enhanced survival in the endothelial population as a whole and how the observed protection affects late CNS necrosis development has yet to be determined. However present results clearly show potential for the use of DNA-binding radioprotectors with limited penetration for investigations into the relative significance of

  15. Cerebrospinal fluid analysis in the context of CNS demyelinating diseases

    Directory of Open Access Journals (Sweden)

    Sandro Luiz de Andrade Matas

    2013-09-01

    Full Text Available The central nervous system demyelinating diseases are a group of disorders with different etiologies, characterized by inflammatory lesions that are associated with loss of myelin and eventually axonal damage. In this group the most studied ones are multiple sclerosis (MS, neuromyelitis optic (NMO and acute disseminated encephalomyelitis (ADEM. The cerebrospinal fluid is essential to differentiate between these different syndromes and to define multiple sclerosis, helping to assess the probability of Clinical Isolated Syndrome turn into multiple sclerosis.

  16. Bortezomib-related neuropathy may mask CNS relapse in multiple myeloma: A call for diligence.

    Science.gov (United States)

    Abid, Muhammad Bilal; De Mel, Sanjay; Abid, Muhammad Abbas; Tan, Kong Bing; Chng, Wee Joo

    2016-07-02

    Neuropathy is a common adverse effect of bortezomib. Isolated central nervous system (CNS) relapse in MM remains exceedingly rare and carries a dismal prognosis. We present an unusual case of bortezomib related neuropathy masking a CNS relapse of MM. A 57-year-old female was diagnosed with standard-risk MM with clinical and cytogenetic features not typically associated with CNS involvement. She was treated with 4 cycles of bortezomib/cyclophosphamide/dexamethasone (VCD) and achieved a VGPR, after which she underwent an autologous stem cell transplant (ASCT) followed by bortezomib maintenance. Six months after ASCT she developed symptoms suggestive of peripheral neuropathy which was attributed to bortezomib. However the symptoms persisted despite discontinuation of bortezomib. Imaging and cerebrospinal fluid analysis subsequently confirmed a CNS relapse. CNS involvement in MM (CNS-MM) is uncommon and is considered an aggressive disease. Recently published literature has reported biomarkers with prognostic potential. However, isolated CNS relapse is even less common; an event which carries a very poor prognosis. Given the heterogeneous neurologic manifestations associated with MM, clinical suspicion may be masked by confounding factors such as bortezomib-based therapy. The disease may further remain incognito if the patient does not exhibit any of the high risk features and biomarkers associated with CNS involvement. In the era of proteasome inhibitor (PtdIns)/immunomodulator (IMID)-based therapy for MM which carries neurologic adverse effects, it is prudent to consider CNS relapse early. This case further highlights the need for more robust biomarkers to predict CNS relapse and use of newer novel agents which demonstrate potential for CNS penetration.

  17. Drug Delivery to CNS: Challenges and Opportunities with Emphasis on Biomaterials Based Drug Delivery Strategies.

    Science.gov (United States)

    Khambhla, Ekta; Shah, Viral; Baviskar, Kalpesh

    2016-01-01

    The current epoch has witnessed a lifestyle impregnated with stress, which is a major cause of several neurological disorders. High morbidity and mortality rate due to neurological diseases and disorders have generated a huge social impact. Despite voluminous research, patients suffering from fatal and/or debilitating CNS diseases such as brain tumors, HIV, encephalopathy, Alzheimer's, epilepsy, Parkinson's, migraine and multiple sclerosis outnumbered those suffering from systemic cancer or heart diseases. The brain being a highly sensitive neuronal organ, has evolved with vasculature barriers, which regulates the efflux and influx of substances to CNS. Treatment of CNS diseases/disorders is challenging because of physiologic, metabolic and biochemical obstacles created by these barriers which comprise mainly of BBB and BCFB. The inability of achieving therapeutically active concentration has become the bottleneck level difficulty, hampering the therapeutic efficiency of several promising drug candidates for CNS related disorders. Parallel maturation of an effective CNS drug delivery strategy with CNS drug discovery is the need of the hour. Recently, the focus of the pharmaceutical community has aggravated in the direction of developing novel and more efficient drug delivery systems, giving the potential of more effective and safer CNS therapies. The present review outlines several hurdles in drug delivery to the CNS along with ideal physicochemical properties desired in drug substance/formulation for CNS delivery. The review also focuses on different conventional and novel strategies for drug delivery to the CNS. The article also assesses and emphasizes on possible benefits of biomaterial based formulations for drug delivery to the CNS.

  18. [Structural CNS abnormalities responsible for coincidental occurrence of endocrine disorders, epilepsy and psychoneurologic disorders in children and adolescents].

    Science.gov (United States)

    Starzyk, Jerzy; Kwiatkowski, Stanisław; Kaciński, Marek; Kroczka, Sławomir; Wójcik, Małgorzata

    2010-01-01

    In the population of children and adolescents, epilepsy affects 0.5-1% of individuals; approximately 3% of general population suffer from non-epileptic seizures, while endocrine disorders are several times more frequent. All of the above factors result in a relatively common non-accidental occurrence of endocrine disorders, epilepsy and neuropsychiatric disorders. However, structural central nervous system (CNS) abnormalities that cause both endocrine and neurologic disorders seem to be markedly less common. No reports addressing this problem are available in the literature. 1) Assessment of the frequency of non-coincidental occurrence of epilepsy and endocrine disorders in inpatients and outpatients with structural CSN abnormalities managed in Department Endocrinology. 2) Presentation of diagnostic and therapeutic difficulties in these patients, and 3) An attempt at defining a common etiology of both disorders. A retrospective analysis of the medical records of the patients with coincidence of endocrine disorders and epilepsy and psycho-neurologic disorders (treated in Chair and Department of Children's and Adolescents Neurology, University Children's Hospital of Krakow or in another pediatric neurology center) and with organic CNS abnormalities (treated or followed up as inpatients and outpatient of Department of Pediatric Surgery, Children's University Hospital of Krakow, was performed. The patients were selected from among several thousands of children treated as inpatients and outpatients of the Department. Various forms of symptomatic and idiopathic epilepsy and other psychoneurological disorders (disorders of behavior and emotions, obsession-compulsion syndromes, stereotypias, aggression, compulsive ideas and movements, anorexia or hypothalamic obesity) coincident with one or more endocrine disorders such as precocious or delayed puberty, multihormonal pituitary deficiency, panhypopituitarism and secondary hypothyroidism were detected in 42 patients with

  19. Effectiveness of Prescription-Based CNS Stimulants on Hospitalization in Patients With Schizophrenia

    DEFF Research Database (Denmark)

    Rohde, Christopher; Polcwiartek, Christoffer; Asztalos, Marton

    2018-01-01

    were used to investigate the effectiveness of CNS stimulants in patients with schizophrenia between 1995 and 2014; a mirror-image model with 605 individuals, using paired t tests and Wilcoxon signed rank tests, and a follow-up study with 789 individuals, using a conditional risk-set model. RESULTS: CNS...

  20. CNS metastasis from malignant uveal melanoma: a clinical and histopathological characterisation

    DEFF Research Database (Denmark)

    Holfort, S K; Lindegaard, J; Isager, P

    2008-01-01

    was observed in two cases (14%). The amount of tumour infiltrating lymphocytes was pronounced in three cases (23%). CONCLUSION: The proportion of uveal melanoma patients having CNS metastasis was 0.7%. Eleven patients had multiple organ metastases, and the average time from the initial CNS symptoms to death...

  1. HB-GAM (pleiotrophin) reverses inhibition of neural regeneration by the CNS extracellular matrix

    Science.gov (United States)

    Paveliev, Mikhail; Fenrich, Keith K.; Kislin, Mikhail; Kuja-Panula, Juha; Kulesskiy, Evgeny; Varjosalo, Markku; Kajander, Tommi; Mugantseva, Ekaterina; Ahonen-Bishopp, Anni; Khiroug, Leonard; Kulesskaya, Natalia; Rougon, Geneviève; Rauvala, Heikki

    2016-01-01

    Chondroitin sulfate (CS) glycosaminoglycans inhibit regeneration in the adult central nervous system (CNS). We report here that HB-GAM (heparin-binding growth-associated molecule; also known as pleiotrophin), a CS-binding protein expressed at high levels in the developing CNS, reverses the role of the CS chains in neurite growth of CNS neurons in vitro from inhibition to activation. The CS-bound HB-GAM promotes neurite growth through binding to the cell surface proteoglycan glypican-2; furthermore, HB-GAM abrogates the CS ligand binding to the inhibitory receptor PTPσ (protein tyrosine phosphatase sigma). Our in vivo studies using two-photon imaging of CNS injuries support the in vitro studies and show that HB-GAM increases dendrite regeneration in the adult cerebral cortex and axonal regeneration in the adult spinal cord. Our findings may enable the development of novel therapies for CNS injuries. PMID:27671118

  2. Therapy of CNS leukemia with intraventricular chemotherapy and low-dose neuraxis radiotherapy

    International Nuclear Information System (INIS)

    Steinherz, P.; Jereb, B.; Galicich, J.

    1985-01-01

    Successful treatment of CNS leukemic relapse has been frustrated by frequent local recurrence and eventual marrow relapse. The authors describe the treatment of meningeal leukemia in 39 children with intrathecal remission induction followed by the placement of an Ommaya reservoir to facilitate the administration and distribution of chemotherapeutic agents into the CSF. Six hundred or 900 rad of craniospinal radiation and maintenance intraventricular and intrathecal chemotherapy was then administered. Systemic reinduction therapy was added in the later cases. Sixteen children (41%) experienced no further events, with 17+ months to 13+ years (median, 25 months) follow-up . Eleven patients (28%) had CNS recurrence, nine (23%) bone marrow (BM) relapse, and two (5%) testicular relapse as the next adverse event. The course of patients with first isolated CNS relapse differed from that of the others. Eleven (69%) of 16 patients treated for first isolated CNS relapse are alive and 9 are event free, while only 35% of patients whose CNS relapse occurred simultaneously or after recurrent disease at other sites are alive (P = .04). Seven of 23 in the later group are event free. The difference is due to the increased incidence of BM relapse in the later group (30% v 6%; P = .04). For patients with first isolated CNS relapse, the life-table median CNS remission duration is 42 months. The projected CNS relapse-free survival and event-free survival 8 to 10 years after CNS relapse are 40% and 32%, respectively. Headache, nausea, and emesis of short duration were frequent during therapy. In three patients, the reservoir had to be removed for infection. No patient suffered neurologic deficit related to the reservoir. The therapy described can reduce the CNS relapse rate with manageable toxicity

  3. An unusual case of calcineurine inhibitor pain syndrome.

    Science.gov (United States)

    Nickavar, Azar; Mehrazma, Mitra; Hallaji, Farideh

    2014-09-01

    Cyclosporine induced pain syndrome (CIPS) is a newly diagnosed complication of calcineurine inhibitors, mainly observed in solid organ and hematopoetic transplantations. The present case is a male child with steroid resistant nephrotic syndrome on low therapeutic level cyclosporine treatment. He presented with intractable and debilitating leg pain, with no reported history of previous injury or trauma. The pain was reluctant to antimicrobial and sedative treatment. MRI revealed bone marrow and soft tissue edema in the mid shaft of patient's right leg. Inspite of unusual manifestations, CIPS was suggested and cyclosporine discontinued. However, the pain did not improve and was resistant to calcium blocker. Subsequently, core decompression was performed as an unusual treatment of CIPS, revealing normal bone morphology. The pain improved rapidly and the patient was discharged a few days later.

  4. TIME COURSE MODIFICATIONS INDUCED BY PERINATAL ASPHYXIA IN RAT CNS

    Directory of Open Access Journals (Sweden)

    Francisco Capani

    2015-04-01

    of estradiol treatment we were able to revert some of these alterations using PI3K/Akt/GSK3. Overall these results demonstrate that synaptic dysfunction following PA might be produced by early changes in the actin organization and long-term misfolding and aggregation of proteins in the PSDs. Therefore, we hypothesize that the synaptic and neuronal cytoskeleton changes induced by PA in the rat CNS could lead to the cellular dysfunction and death in adult animals. Estradiol appears as a new therapeutic tool to slacken the damage induces by perinatal asphyxia on the CNS.

  5. Cerebral toxoplasmosis and lymphoma in patients with Acquired Immunodeficiency Syndrome

    International Nuclear Information System (INIS)

    Laviopierre, A.M.; Lawler, G.A.

    1989-01-01

    Toxoplasmosis now constitutes a relatively frequent central nervous system (CNS) complication of AIDS, primary CNS lymphoma being far less common. CT scanning using the double-dose delayed (D-D-D) scan technique has proved an effective way of helping in the diagnosis of these complications. 16 patients with CNS complications of the acquired immunodeficiency syndrome (AIDS) are described. All patients were male homosexuals. The most common demonstrable lesion in the parenchyma was toxoplasmosis, which produced an area of focal oedema, usually containing a central zone of nodular or ring-shaped enhancement. Cerebral atrophy was also a common finding. One patient had diffuse peri-ventricular lymphomatous infiltration, and a further two patients had both cerebral toxoplasmosis and lymphoma. A delayed double dose contrast examination appears to be the most accurate method of outlining the total extent of CNS disease in these patients. 11 refs., 7 figs., 2 tabs

  6. Serotonin syndrome

    Science.gov (United States)

    Hyperserotonemia; Serotonergic syndrome; Serotonin toxicity; SSRI - serotonin syndrome; MAO - serotonin syndrome ... brain area. For example, you can develop this syndrome if you take migraine medicines called triptans together ...

  7. Growth of Malignant Non-CNS Tumors Alters Brain Metabolome

    Science.gov (United States)

    Kovalchuk, Anna; Nersisyan, Lilit; Mandal, Rupasri; Wishart, David; Mancini, Maria; Sidransky, David; Kolb, Bryan; Kovalchuk, Olga

    2018-01-01

    Cancer survivors experience numerous treatment side effects that negatively affect their quality of life. Cognitive side effects are especially insidious, as they affect memory, cognition, and learning. Neurocognitive deficits occur prior to cancer treatment, arising even before cancer diagnosis, and we refer to them as “tumor brain.” Metabolomics is a new area of research that focuses on metabolome profiles and provides important mechanistic insights into various human diseases, including cancer, neurodegenerative diseases, and aging. Many neurological diseases and conditions affect metabolic processes in the brain. However, the tumor brain metabolome has never been analyzed. In our study we used direct flow injection/mass spectrometry (DI-MS) analysis to establish the effects of the growth of lung cancer, pancreatic cancer, and sarcoma on the brain metabolome of TumorGraft™ mice. We found that the growth of malignant non-CNS tumors impacted metabolic processes in the brain, affecting protein biosynthesis, and amino acid and sphingolipid metabolism. The observed metabolic changes were similar to those reported for neurodegenerative diseases and brain aging, and may have potential mechanistic value for future analysis of the tumor brain phenomenon. PMID:29515623

  8. Role of galectin-3 in prion infections of the CNS

    International Nuclear Information System (INIS)

    Mok, Simon W.F.; Riemer, Constanze; Madela, Kazimierz; Hsu, Daniel K.; Liu, Fu-Tong; Gueltner, Sandra; Heise, Ines; Baier, Michael

    2007-01-01

    Galectin-3 is a multi-functional protein and participates in mediating inflammatory reactions. The pronounced overexpression of galectin-3 in prion-infected brain tissue prompted us to study the role of this protein in a murine prion model. Immunofluorescence double-labelling identified microglia as the major cell type expressing galectin-3. Ablation of galectin-3 did not affect PrP Sc -deposition and development of gliosis. However, galectin-3 -/- -mice showed prolonged survival times upon intracerebral and peripheral scrapie infections. Moreover, protein levels of the lysosomal activation marker LAMP-2 were markedly reduced in prion-infected galectin-3 -/- -mice suggesting a role of galectin-3 in regulation of lysosomal functions. Lower mRNA levels of Beclin-1 and Atg5 in prion-infected wild-type and galectin-3 -/- -mice indicated an impairment of autophagy although autophagosome formation was unchanged. The results point towards a detrimental role of galectin-3 in prion infections of the CNS and suggest that endo-/lysosomal dysfunction in combination with reduced autophagy may contribute to disease development

  9. Fluids and barriers of the CNS: a historical viewpoint

    Directory of Open Access Journals (Sweden)

    Liddelow Shane A

    2011-01-01

    Full Text Available Abstract Tracing the exact origins of modern science can be a difficult but rewarding pursuit. It is possible for the astute reader to follow the background of any subject through the many important surviving texts from the classical and ancient world. While empirical investigations have been described by many since the time of Aristotle and scientific methods have been employed since the Middle Ages, the beginnings of modern science are generally accepted to have originated during the 'scientific revolution' of the 16th and 17th centuries in Europe. The scientific method is so fundamental to modern science that some philosophers consider earlier investigations as 'pre-science'. Notwithstanding this, the insight that can be gained from the study of the beginnings of a subject can prove important in the understanding of work more recently completed. As this journal undergoes an expansion in focus and nomenclature from cerebrospinal fluid (CSF into all barriers of the central nervous system (CNS, this review traces the history of both the blood-CSF and blood-brain barriers from as early as it was possible to find references, to the time when modern concepts were established at the beginning of the 20th century.

  10. Electrophysiological CNS-processes related to associative learning in humans.

    Science.gov (United States)

    Christoffersen, Gert R J; Schachtman, Todd R

    2016-01-01

    The neurophysiology of human associative memory has been studied with electroencephalographic techniques since the 1930s. This research has revealed that different types of electrophysiological processes in the human brain can be modified by conditioning: sensory evoked potentials, sensory induced gamma-band activity, periods of frequency-specific waves (alpha and beta waves, the sensorimotor rhythm and the mu-rhythm) and slow cortical potentials. Conditioning of these processes has been studied in experiments that either use operant conditioning or repeated contingent pairings of conditioned and unconditioned stimuli (classical conditioning). In operant conditioning, the appearance of a specific brain process is paired with an external stimulus (neurofeedback) and the feedback enables subjects to obtain varying degrees of control of the CNS-process. Such acquired self-regulation of brain activity has found practical uses for instance in the amelioration of epileptic seizures, Autism Spectrum Disorders (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). It has also provided communicative means of assistance for tetraplegic patients through the use of brain computer interfaces. Both extra and intracortically recorded signals have been coupled with contingent external feedback. It is the aim for this review to summarize essential results on all types of electromagnetic brain processes that have been modified by classical or operant conditioning. The results are organized according to type of conditioned EEG-process, type of conditioning, and sensory modalities of the conditioning stimuli. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Stress preconditioning of spreading depression in the locust CNS.

    Directory of Open Access Journals (Sweden)

    Corinne I Rodgers

    Full Text Available Cortical spreading depression (CSD is closely associated with important pathologies including stroke, seizures and migraine. The mechanisms underlying SD in its various forms are still incompletely understood. Here we describe SD-like events in an invertebrate model, the ventilatory central pattern generator (CPG of locusts. Using K(+ -sensitive microelectrodes, we measured extracellular K(+ concentration ([K(+](o in the metathoracic neuropile of the CPG while monitoring CPG output electromyographically from muscle 161 in the second abdominal segment to investigate the role K(+ in failure of neural circuit operation induced by various stressors. Failure of ventilation in response to different stressors (hyperthermia, anoxia, ATP depletion, Na(+/K(+ ATPase impairment, K(+ injection was associated with a disturbance of CNS ion homeostasis that shares the characteristics of CSD and SD-like events in vertebrates. Hyperthermic failure was preconditioned by prior heat shock (3 h, 45 degrees C and induced-thermotolerance was associated with an increase in the rate of clearance of extracellular K(+ that was not linked to changes in ATP levels or total Na(+/K(+ ATPase activity. Our findings suggest that SD-like events in locusts are adaptive to terminate neural network operation and conserve energy during stress and that they can be preconditioned by experience. We propose that they share mechanisms with CSD in mammals suggesting a common evolutionary origin.

  12. Human abuse liability evaluation of CNS stimulant drugs.

    Science.gov (United States)

    Romach, Myroslava K; Schoedel, Kerri A; Sellers, Edward M

    2014-12-01

    Psychoactive drugs that increase alertness, attention and concentration and energy, while also elevating mood, heart rate and blood pressure are referred to as stimulants. Despite some overlapping similarities, stimulants cannot be easily categorized by their chemical structure, mechanism of action, receptor binding profile, effects on monoamine uptake, behavioral pharmacology (e.g., effects on locomotion, temperature, and blood pressure), therapeutic indication or efficacy. Because of their abuse liability, a pre-market assessment of abuse potential is required for drugs that show stimulant properties; this review article focuses on the clinical aspects of this evaluation. This includes clinical trial adverse events, evidence of diversion or tampering, overdoses and the results of a human abuse potential study. While there are different types of human experimental studies that can be employed to evaluate stimulant abuse potential (e.g., drug discrimination, self-administration), only the human abuse potential study and clinical trial adverse event data are required for drug approval. The principal advances that have improved human abuse potential studies include using study enrichment strategies (pharmacologic qualification), larger sample sizes, better selection of endpoints and measurement strategies and more carefully considered interpretation of data. Because of the methodological advances, comparisons of newer studies with historical data is problematic and may contribute to a biased regulatory framework for the evaluation of newer stimulant-like drugs, such as A2 antagonists. This article is part of the Special Issue entitled 'CNS Stimulants'. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. The mastermind approach to CNS drug therapy: translational prediction of human brain distribution, target site kinetics, and therapeutic effects

    OpenAIRE

    de Lange, Elizabeth CM

    2013-01-01

    Despite enormous advances in CNS research, CNS disorders remain the world?s leading cause of disability. This accounts for more hospitalizations and prolonged care than almost all other diseases combined, and indicates a high unmet need for good CNS drugs and drug therapies. Following dosing, not only the chemical properties of the drug and blood?brain barrier (BBB) transport, but also many other processes will ultimately determine brain target site kinetics and consequently the CNS effects. ...

  14. When the Tail Can't Wag the Dog: The Implications of CNS-Intrinsic Initiation of Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Deirdre S Davis

    2009-04-01

    Full Text Available The CNS (central nervous system is unquestionably the central organ that regulates directly or indirectly all physiological systems in the mammalian body. Yet, when considering the defence of the CNS from pathogens, the CNS has often been considered passive and subservient to the pro-inflammatory responses of the immune system. In this view, neuroinflammatory disorders are examples of when the tail (the immune system wags the dog (the CNS to the detriment of an individual's function and survival.

  15. Acquired Demyelinating Syndromes: Focus on Neuromyelitis Optica and childhood-onset Multiple Sclerosis

    NARCIS (Netherlands)

    E.D. van Pelt - Gravesteijn (Daniëlle)

    2016-01-01

    markdownabstractAcquired demyelinating syndromes (ADS) cover a broad spectrum of central nervous system (CNS) inflammatory demyelinating syndromes, of which multiple sclerosis (MS) is the most common subtype. This thesis focuses on two relatively rare clinical subtypes of ADS: neuromyelitis optica

  16. The retina as a window to the brain-from eye research to CNS disorders.

    Science.gov (United States)

    London, Anat; Benhar, Inbal; Schwartz, Michal

    2013-01-01

    Philosophers defined the eye as a window to the soul long before scientists addressed this cliché to determine its scientific basis and clinical relevance. Anatomically and developmentally, the retina is known as an extension of the CNS; it consists of retinal ganglion cells, the axons of which form the optic nerve, whose fibres are, in effect, CNS axons. The eye has unique physical structures and a local array of surface molecules and cytokines, and is host to specialized immune responses similar to those in the brain and spinal cord. Several well-defined neurodegenerative conditions that affect the brain and spinal cord have manifestations in the eye, and ocular symptoms often precede conventional diagnosis of such CNS disorders. Furthermore, various eye-specific pathologies share characteristics of other CNS pathologies. In this Review, we summarize data that support examination of the eye as a noninvasive approach to the diagnosis of select CNS diseases, and the use of the eye as a valuable model to study the CNS. Translation of eye research to CNS disease, and deciphering the role of immune cells in these two systems, could improve our understanding and, potentially, the treatment of neurodegenerative disorders.

  17. Observations at the CNS-PNS border of ventral roots connected to a neuroma

    Directory of Open Access Journals (Sweden)

    Sten Remahl

    2010-10-01

    Full Text Available Previous studies have shown that numerous sprouts originating from a neuroma, after nerve injury in neonatal animals, can invade spinal nerve roots. In this study the border between the central and peripheral nervous system (CNS-PNS border of ventral roots in kittens was examined with both light and electron microscopy after early postnatal sciatic nerve resection. A transient ingrowth of substance P positive axons was observed into the CNS, but no spouts remained 6 weeks after the injury. Using serial sections and electron microscopy it was possible to identify small bundles of unmyelinated axons that penetrated from the root fascicles for a short distance into the CNS. These axons ended blindly, sometimes with a growth cone-like terminal swelling filled with vesicles. The axon bundles were accompanied by p75 positive cells in both the root fascicles and the pia mater, but not in the CNS. It may thus be suggested that neurotrophin presenting p75 positive cells could facilitate axonal growth into the pia mater and that the lack of such cells in the CNS compartment might contribute to the failure of growth into the CNS. A maldevelopment of myelin sheaths at the CNS-PNS border of motor axons was observed and it seems possible that this could have consequences for the propagation of action potential across this region after neonatal nerve injury.

  18. Glucocorticoid treatment of MCMV infected newborn mice attenuates CNS inflammation and limits deficits in cerebellar development.

    Directory of Open Access Journals (Sweden)

    Kate Kosmac

    2013-03-01

    Full Text Available Infection of the developing fetus with human cytomegalovirus (HCMV is a major cause of central nervous system disease in infants and children; however, mechanism(s of disease associated with this intrauterine infection remain poorly understood. Utilizing a mouse model of HCMV infection of the developing CNS, we have shown that peripheral inoculation of newborn mice with murine CMV (MCMV results in CNS infection and developmental abnormalities that recapitulate key features of the human infection. In this model, animals exhibit decreased granule neuron precursor cell (GNPC proliferation and altered morphogenesis of the cerebellar cortex. Deficits in cerebellar cortical development are symmetric and global even though infection of the CNS results in a non-necrotizing encephalitis characterized by widely scattered foci of virus-infected cells with mononuclear cell infiltrates. These findings suggested that inflammation induced by MCMV infection could underlie deficits in CNS development. We investigated the contribution of host inflammatory responses to abnormal cerebellar development by modulating inflammatory responses in infected mice with glucocorticoids. Treatment of infected animals with glucocorticoids decreased activation of CNS mononuclear cells and expression of inflammatory cytokines (TNF-α, IFN-β and IFNγ in the CNS while minimally impacting CNS virus replication. Glucocorticoid treatment also limited morphogenic abnormalities and normalized the expression of developmentally regulated genes within the cerebellum. Importantly, GNPC proliferation deficits were normalized in MCMV infected mice following glucocorticoid treatment. Our findings argue that host inflammatory responses to MCMV infection contribute to deficits in CNS development in MCMV infected mice and suggest that similar mechanisms of disease could be responsible for the abnormal CNS development in human infants infected in-utero with HCMV.

  19. Imaging Findings of Central Nervous System Vasculitis Associated with Goodpasture's Syndrome: a Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jee Young; Ahn, Kook Jin; Jung, Jung Im; Jung, So Lyung; Kim, Bum Soo; Hahn, Seong Tae [College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)

    2007-12-15

    We report a rare case of CNS vasculitis associated with Goodpasture's syndrome in a 34-year-old man, who presented with a seizure and sudden onset of right sided weakness. He also had recurrent hemoptysis of one month's duration. Goodpasture's syndrome is histologically diagnosed by intense linear deposits of IgG along the glomerular basement membrane in both renal and lung tissues. oodpasture's syndrome is a rare disease, characterized by rapidly progressive glomerulonephritis, diffuse pulmonary hemorrhage and circulating antiglomerular basement membrane antibody (anti-GBM antibody). Central nervous system (CNS) manifestations in Goodpasture's syndrome are extremely rare, with only a few cases having been reported in the literature (8 10). Therefore, we present our imaging findings of CNS vasculitis associated with Goodpasture's syndrome, together with a review of the relevant literature. In summary, CNS vasculitis associated with Goodpasture's syndrome is extremely rare. Awareness of the imaging findings, as well as the clinical significance of CNS vasculitis associated with Goodpasture's syndrome, can be helpful in making the correct diagnosis and subsequent management of this rare condition.

  20. Carbon monoxide inhalation increases microparticles causing vascular and CNS dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Jiajun; Yang, Ming [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Kosterin, Paul [Department of Neuroscience, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Salzberg, Brian M. [Department of Physiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Milovanova, Tatyana N.; Bhopale, Veena M. [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States); Thom, Stephen R., E-mail: sthom@smail.umaryland.edu [Department of Emergency Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 (United States)

    2013-12-01

    We hypothesized that circulating microparticles (MPs) play a role in pro-inflammatory effects associated with carbon monoxide (CO) inhalation. Mice exposed for 1 h to 100 ppm CO or more exhibit increases in circulating MPs derived from a variety of vascular cells as well as neutrophil activation. Tissue injury was quantified as 2000 kDa dextran leakage from vessels and as neutrophil sequestration in the brain and skeletal muscle; and central nervous system nerve dysfunction was documented as broadening of the neurohypophysial action potential (AP). Indices of injury occurred following exposures to 1000 ppm for 1 h or to 1000 ppm for 40 min followed by 3000 ppm for 20 min. MPs were implicated in causing injuries because infusing the surfactant MP lytic agent, polyethylene glycol telomere B (PEGtB) abrogated elevations in MPs, vascular leak, neutrophil sequestration and AP prolongation. These manifestations of tissue injury also did not occur in mice lacking myeloperoxidase. Vascular leakage and AP prolongation were produced in naïve mice infused with MPs that had been obtained from CO poisoned mice, but this did not occur with MPs obtained from control mice. We conclude that CO poisoning triggers elevations of MPs that activate neutrophils which subsequently cause tissue injuries. - Highlights: • Circulating microparticles (MPs) increase in mice exposed to 100 ppm CO or more. • MPs are lysed by infusing the surfactant polyethylene glycol telomere B. • CO-induced MPs cause neutrophil activation, vascular leak and CNS dysfunction. • Similar tissue injuries do not arise with MPs obtained from air-exposed, control mice.

  1. CLIPPERS among patients diagnosed with non-specific CNS neuroinflammatory diseases

    DEFF Research Database (Denmark)

    Kerrn-Jespersen, B M; Lindelof, M; Illes, Zsolt

    2014-01-01

    Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS) is an inflammatory CNS disorder characterized by 1) subacute onset of cerebellar and brainstem symptoms, 2) peripontine contrast-enhancing perivascular lesions with a "salt-and-pepper" appeara...

  2. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

    NARCIS (Netherlands)

    Sturm, Dominik; Orr, Brent A.; Toprak, Umut H.; Hovestadt, Volker; Jones, David T. W.; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A.; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J.; Balasubramanian, Gnanaprakash; Worst, Barbara C.; Pajtler, Kristian W.; Brabetz, Sebastian; Johann, Pascal D.; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M.; Remke, Marc; Phillips, Joanna J.; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C.; Schniederjan, Matthew J.; Santi, Mariarita; Buccoliero, Anna M.; Dahiya, Sonika; Kramm, Christof M.; von Bueren, André O.; von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C.; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V. Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U.; Shalaby, Tarek; Grotzer, Michael; van Meter, Timothy; Monoranu, Camelia-Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S.; Taylor, Michael D.; Jones, Chris; Jabado, Nada; Karajannis, Matthias A.; Eils, Roland; Schlesner, Matthias; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M.; Ellison, David W.; Korshunov, Andrey; Kool, Marcel

    2016-01-01

    Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally

  3. New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

    NARCIS (Netherlands)

    Sturm, Dominik; Orr, Brent A.; Toprak, Umut H.; Hovestadt, Volker; Jones, David T W; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A.; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J.; Balasubramanian, Gnanaprakash; Worst, Barbara C.; Pajtler, Kristian W.; Brabetz, Sebastian; Johann, Pascal D.; Sahm, Felix; Reimand, Jüri; Mackay, Alan; Carvalho, Diana M.; Remke, Marc; Phillips, Joanna J.; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Łastowska, Maria; Grajkowska, Wiesława; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lötsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C.; Schniederjan, Matthew J.; Santi, Mariarita; Buccoliero, Anna M.; Dahiya, Sonika; Kramm, Christof M.; Von Bueren, André O.; Von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Frühwald, Michael C.; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rößler, Jochen; Schüller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V. Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U.; Shalaby, Tarek; Grotzer, Michael; Van Meter, Timothy; Monoranu, Camelia Maria; Felsberg, Jörg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; Van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S.; Taylor, Michael D.; Jones, Chris; Jabado, Nada; Karajannis, Matthias A.; Eils, Roland; Schlesner, Matthias; Lichter, Peter; Von Deimling, Andreas; Pfister, Stefan M.; Ellison, David W.; Korshunov, Andrey; Kool, Marcel

    2016-01-01

    Summary Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of

  4. Netrin-1 Confines Rhombic Lip-Derived Neurons to the CNS

    Directory of Open Access Journals (Sweden)

    Andrea R. Yung

    2018-02-01

    Full Text Available During brainstem development, newborn neurons originating from the rhombic lip embark on exceptionally long migrations to generate nuclei important for audition, movement, and respiration. Along the way, this highly motile population passes several cranial nerves yet remains confined to the CNS. We found that Ntn1 accumulates beneath the pial surface separating the CNS from the PNS, with gaps at nerve entry sites. In mice null for Ntn1 or its receptor DCC, hindbrain neurons enter cranial nerves and migrate into the periphery. CNS neurons also escape when Ntn1 is selectively lost from the sub-pial region (SPR, and conversely, expression of Ntn1 throughout the mutant hindbrain can prevent their departure. These findings identify a permissive role for Ntn1 in maintaining the CNS-PNS boundary. We propose that Ntn1 confines rhombic lip-derived neurons by providing a preferred substrate for tangentially migrating neurons in the SPR, preventing their entry into nerve roots.

  5. Micropituitarism and cortical dysplasia: an unknown association of two uncommon CNS disorders

    International Nuclear Information System (INIS)

    Blinder, G.; Corat-Simon, J.; Hershkovitz, E.

    2001-01-01

    We describe a case of two known pathologies of the CNS in an unusual association: the concomitant presentation of the micropituitarism and cortical dysplasia. To our knowledge, this association is unreported to date. (orig.)

  6. Micropituitarism and cortical dysplasia: an unknown association of two uncommon CNS disorders

    Energy Technology Data Exchange (ETDEWEB)

    Blinder, G. [MAR Bikur Cholim Hospital Jerusalem (MOR-MAR), Jerusalem (Israel); Corat-Simon, J. [Dept. of Radiology, Assaf Harofeh Medical Center, Zrifin, Beer Jakov (Israel); Hershkovitz, E. [Dept. of Pediatrics, Soroka Medical Center, Beer Sheba (Israel)

    2001-06-01

    We describe a case of two known pathologies of the CNS in an unusual association: the concomitant presentation of the micropituitarism and cortical dysplasia. To our knowledge, this association is unreported to date. (orig.)

  7. Beals Syndrome

    Science.gov (United States)

    ... the syndrome. How does Beals syndrome compare with Marfan syndrome? People with Beals syndrome have many of the ... bone) and aortic enlargement problems as people with Marfan syndrome, and treatments for these problems are the same. ...

  8. Drug induced increases in CNS dopamine alter monocyte, macrophage and T cell functions: implications for HAND

    Science.gov (United States)

    Gaskill, Peter J.; Calderon, Tina M.; Coley, Jacqueline S.; Berman, Joan W.

    2013-01-01

    Central nervous system (CNS) complications resulting from HIV infection remain a major public health problem as individuals live longer due to the success of combined antiretroviral therapy (cART). As many as 70% of HIV infected people have HIV associated neurocognitive disorders (HAND). Many HIV infected individuals abuse drugs, such as cocaine, heroin or methamphetamine, that may be important cofactors in the development of HIV CNS disease. Despite different mechanisms of action, all drugs of abuse increase extracellular dopamine in the CNS. The effects of dopamine on HIV neuropathogenesis are not well understood, and drug induced increases in CNS dopamine may be a common mechanism by which different types of drugs of abuse impact the development of HAND. Monocytes and macrophages are central to HIV infection of the CNS and to HAND. While T cells have not been shown to be a major factor in HIV-associated neuropathogenesis, studies indicate that T cells may play a larger role in the development of HAND in HIV infected drug abusers. Drug induced increases in CNS dopamine may dysregulate functions of, or increase HIV infection in, monocytes, macrophages and T cells in the brain. Thus, characterizing the effects of dopamine on these cells is important for understanding the mechanisms that mediate the development of HAND in drug abusers. PMID:23456305

  9. [The problems of diagnosis and correction of autism in children (an example of Asperger's syndrome)].

    Science.gov (United States)

    Iovchuk, N M; Severnyĭ, A A

    Based on the analysis of literature and own clinical experience, we discuss diagnostic issues of early autistic disorders in children. Main differential-diagnostic signs that permit to differentiate mild forms of autism in childhood diagnosed as Asperger's syndrome from childhood schizophrenia, residual organic CNS damage, circular affective disorders are described. Cases of Asperger's syndrome followed up for many years and recommendations for social and psychological adaptation of children and adolescents with Asperger's syndrome in different age periods are presented.

  10. CNS involvement in AIDS: spectrum of CT and MR findings

    International Nuclear Information System (INIS)

    Thurnher, M.M.; Thurnher, S.A.; Schindler, E.

    1997-01-01

    The brain may be affected by a variety of abnormalities in association with human immunodeficiency virus (HIV) infection. Knowledge of their existence and characteristic imaging features are important to radiologists for detection, diagnosis, and initiation of an appropriate treatment. Although there is a considerable overlap in the imaging characteristics of different entities, some findings are found to be very suggestive of a particular disease. The CT and MR imaging techniques are commonly used in the diagnosis of neurological disorders in acquired immunodeficiency syndrome (AIDS) patients, to verify treatment response and to guide brain biopsy. This review attempts to describe CT and MR features of infectious and malignant brain disorders in HIV-seropositive patients. (orig.). With 13 figs

  11. Cushing syndrome

    Science.gov (United States)

    Hypercortisolism; Cortisol excess; Glucocorticoid excess - Cushing syndrome ... The most common cause of Cushing syndrome is taking too much ... Cushing syndrome . Prednisone, dexamethasone, and prednisolone ...

  12. LEOPARD syndrome

    Science.gov (United States)

    Multiple lentigines syndrome; Noonan syndrome with multiple lentigines ... Genetics Home Reference -- ghr.nlm.nih.gov/condition/noonan-syndrome-with-multiple-lentigines National Organization for Rare Disorders -- ...

  13. The Greig cephalopolysyndactyly syndrome

    Directory of Open Access Journals (Sweden)

    Biesecker Leslie G

    2008-04-01

    Full Text Available Abstract The Greig cephalopolysyndactyly syndrome (GCPS is a pleiotropic, multiple congenital anomaly syndrome. It is rare, but precise estimates of incidence are difficult to determine, as ascertainment is erratic (estimated range 1–9/1,000,000. The primary findings include hypertelorism, macrocephaly with frontal bossing, and polysyndactyly. The polydactyly is most commonly preaxial of the feet and postaxial in the hands, with variable cutaneous syndactyly, but the limb findings vary significantly. Other low frequency findings include central nervous system (CNS anomalies, hernias, and cognitive impairment. GCPS is caused by loss of function mutations in the GLI3 transcription factor gene and is inherited in an autosomal dominant pattern. The disorder is allelic to the Pallister-Hall syndrome and one form of the acrocallosal syndrome. Clinical diagnosis is challenging because the findings of GCPS are relatively non-specific, and no specific and sensitive clinical have been delineated. For this reason, we have proposed a combined clinical-molecular definition for the syndrome. A presumptive diagnosis of GCPS can be made if the patient has the classic triad of preaxial polydactyly with cutaneous syndactyly of at least one limb, hypertelorism, and macrocephaly. Patients with a phenotype consistent with GCPS (but which may not manifest all three attributes listed above and a GLI3 mutation may be diagnosed definitively with GCPS. In addition, persons with a GCPS-consistent phenotype who are related to a definitively diagnosed family member in a pattern consistent with autosomal dominant inheritance may be diagnosed definitively as well. Antenatal molecular diagnosis is technically straightforward to perform. Differential diagnoses include preaxial polydactyly type 4, the GCPS contiguous gene syndrome, acrocallosal syndrome, Gorlin syndrome, Carpenter syndrome, and Teebi syndrome. Treatment of the disorder is symptomatic, with plastic or

  14. Contribution of Schwann Cells to Remyelination in a Naturally Occurring Canine Model of CNS Neuroinflammation.

    Directory of Open Access Journals (Sweden)

    Kristel Kegler

    Full Text Available Gliogenesis under pathophysiological conditions is of particular clinical relevance since it may provide evidence for regeneration promoting cells recruitable for therapeutic purposes. There is evidence that neurotrophin receptor p75 (p75NTR-expressing cells emerge in the lesioned CNS. However, the phenotype and identity of these cells, and signals triggering their in situ generation under normal conditions and certain pathological situations has remained enigmatic. In the present study, we used a spontaneous, idiopathic and inflammatory CNS condition in dogs with prominent lympho-histiocytic infiltration as a model to study the phenotype of Schwann cells and their relation to Schwann cell remyelination within the CNS. Furthermore, the phenotype of p75NTR-expressing cells within the injured CNS was compared to their counter-part in control sciatic nerve and after peripheral nerve injury. In addition, organotypic slice cultures were used to further elucidate the origin of p75NTR-positive cells. In cerebral and cerebellar white and grey matter lesions as well as in the brain stem, p75NTR-positive cells co-expressed the transcription factor Sox2, but not GAP-43, GFAP, Egr2/Krox20, periaxin and PDGFR-α. Interestingly, and contrary to the findings in control sciatic nerves, p75NTR-expressing cells only co-localized with Sox2 in degenerative neuropathy, thus suggesting that such cells might represent dedifferentiated Schwann cells both in the injured CNS and PNS. Moreover, effective Schwann cell remyelination represented by periaxin- and P0-positive mature myelinating Schwann cells, was strikingly associated with the presence of p75NTR/Sox2-expressing Schwann cells. Intriguingly, the emergence of dedifferentiated Schwann cells was not affected by astrocytes, and a macrophage-dominated inflammatory response provided an adequate environment for Schwann cells plasticity within the injured CNS. Furthermore, axonal damage was reduced in brain stem areas

  15. CNS infiltration of peripheral immune cells: D-Day for neurodegenerative disease?

    Science.gov (United States)

    Rezai-Zadeh, Kavon; Gate, David; Town, Terrence

    2009-12-01

    While the central nervous system (CNS) was once thought to be excluded from surveillance by immune cells, a concept known as "immune privilege," it is now clear that immune responses do occur in the CNS-giving rise to the field of neuroimmunology. These CNS immune responses can be driven by endogenous (glial) and/or exogenous (peripheral leukocyte) sources and can serve either productive or pathological roles. Recent evidence from mouse models supports the notion that infiltration of peripheral monocytes/macrophages limits progression of Alzheimer's disease pathology and militates against West Nile virus encephalitis. In addition, infiltrating T lymphocytes may help spare neuronal loss in models of amyotrophic lateral sclerosis. On the other hand, CNS leukocyte penetration drives experimental autoimmune encephalomyelitis (a mouse model for the human demyelinating disease multiple sclerosis) and may also be pathological in both Parkinson's disease and human immunodeficiency virus encephalitis. A critical understanding of the cellular and molecular mechanisms responsible for trafficking of immune cells from the periphery into the diseased CNS will be key to target these cells for therapeutic intervention in neurodegenerative diseases, thereby allowing neuroregenerative processes to ensue.

  16. Current approaches to enhance CNS delivery of drugs across the brain barriers

    Directory of Open Access Journals (Sweden)

    Lu CT

    2014-05-01

    Full Text Available Cui-Tao Lu,1 Ying-Zheng Zhao,2,3 Ho Lun Wong,4 Jun Cai,5 Lei Peng,2 Xin-Qiao Tian1 1The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou City, Zhejiang Province, People’s Republic of China; 2Hainan Medical College, Haikou City, Hainan Province, People’s Republic of China; 3College of Pharmaceutical Sciences, Wenzhou Medical University, Zhejiang Province, People’s Republic of China; 4School of Pharmacy, Temple University, Philadelphia, PA, USA; 5Departments of Pediatrics and Anatomical Sciences and Neurobiology, University of Louisville School of Medicine Louisville, KY, USA Abstract: Although many agents have therapeutic potentials for central nervous system (CNS diseases, few of these agents have been clinically used because of the brain barriers. As the protective barrier of the CNS, the blood–brain barrier and the blood–cerebrospinal fluid barrier maintain the brain microenvironment, neuronal activity, and proper functioning of the CNS. Different strategies for efficient CNS delivery have been studied. This article reviews the current approaches to open or facilitate penetration across these barriers for enhanced drug delivery to the CNS. These approaches are summarized into three broad categories: noninvasive, invasive, and miscellaneous techniques. The progresses made using these approaches are reviewed, and the associated mechanisms and problems are discussed. Keywords: drug delivery system, blood–brain barrier (BBB, central nervous system, brain-targeted therapy, cerebrospinal fluid (CSF

  17. Foxp3+ regulatory T cells control persistence of viral CNS infection.

    Directory of Open Access Journals (Sweden)

    Dajana Reuter

    Full Text Available We earlier established a model of a persistent viral CNS infection using two week old immunologically normal (genetically unmodified mice and recombinant measles virus (MV. Using this model infection we investigated the role of regulatory T cells (Tregs as regulators of the immune response in the brain, and assessed whether the persistent CNS infection can be modulated by manipulation of Tregs in the periphery. CD4(+ CD25(+ Foxp3(+ Tregs were expanded or depleted during the persistent phase of the CNS infection, and the consequences for the virus-specific immune response and the extent of persistent infection were analyzed. Virus-specific CD8(+ T cells predominantly recognising the H-2D(b-presented viral hemagglutinin epitope MV-H(22-30 (RIVINREHL were quantified in the brain by pentamer staining. Expansion of Tregs after intraperitoneal (i.p. application of the superagonistic anti-CD28 antibody D665 inducing transient immunosuppression caused increased virus replication and spread in the CNS. In contrast, depletion of Tregs using diphtheria toxin (DT in DEREG (depletion of regulatory T cells-mice induced an increase of virus-specific CD8(+ effector T cells in the brain and caused a reduction of the persistent infection. These data indicate that manipulation of Tregs in the periphery can be utilized to regulate virus persistence in the CNS.

  18. Detail Design of the hydrogen system and the gas blanketing system for the HANARO-CNS

    International Nuclear Information System (INIS)

    Choi, Jung Woon; Kim, Hark Rho; Kim, Young Ki; Wu, Sang Ik; Kim, Bong Su; Lee, Yong Seop

    2007-04-01

    The cold neutron source (CNS), which will be installed in the vertical CN hole of the reflector tank at HANARO, makes thermal neutrons to moderate into the cold neutrons with the ranges of 0.1 ∼ 10 meV passing through a moderator at about 22K. A moderator to produce cold neutrons is liquid hydrogen, which liquefies by the heat transfer with cryogenic helium flowing from the helium refrigeration system (HRS). Because of its installed location, the hydrogen system is designed to be surrounded by the gas blanketing system to notify the leakage on the system and to prevent hydrogen leakage out of the CNS. The hydrogen system, consisted of hydrogen charging unit, hydrogen storage unit, hydrogen buffer tank, and hydrogen piping, is designed to smoothly and safely supply hydrogen to and to draw back hydrogen from the IPA of the CNS under the HRS operation mode. Described is that calculation for total required hydrogen amount in the CNS as well as operation schemes of the hydrogen system. The gas blanketing system (GBS) is designed for the supply of the compressed nitrogen gas into the air pressurized valves for the CNS, to isolate the hydrogen system from the air and the water, and to prevent air or water intrusion into the vacuum system as well as the hydrogen system. All detail descriptions are shown inhere as well as the operation scheme for the GBS

  19. Fanconi syndrome

    Science.gov (United States)

    De Toni-Fanconi syndrome ... Fanconi syndrome can be caused by faulty genes, or it may result later in life due to kidney damage. Sometimes the cause of Fanconi syndrome is unknown. Common causes of Fanconi syndrome in ...

  20. Duane Syndrome

    Science.gov (United States)

    ... Frequently Asked Questions Español Condiciones Chinese Conditions Duane Syndrome En Español Read in Chinese What is Duane Syndrome? Duane syndrome, also called Duane retraction syndrome (DRS), ...

  1. Psychosis, Mood and Behavioral Disorders in Usher Syndrome: Review of the Literature.

    Science.gov (United States)

    Domanico, Daniela; Fragiotta, Serena; Cutini, Alessandro; Grenga, Pier Luigi; Vingolo, Enzo Maria

    2015-01-01

    The aim of this review is to focus the current knowledge about mental and behavioral disorders in Usher syndrome. Previous studies described the presence of various mental disorders associated with Usher syndrome, suggesting possible mechanisms of association between these disorders. The most common manifestations are schizophrenia-like disorder and psychotic symptoms. Mood and behavioral disorders are rarely described, and often are associated with more complex cases in co-occurrence with other psychiatric disorders. Neuroimaging studies reported diffuse involvement of central nervous system (CNS) in Usher patients, suggesting a possible role of CNS damage in the pathogenesis of psychiatric manifestations. Genetic hypothesis and stress-related theories have also been proposed.

  2. Interactions of the histamine and hypocretin systems in CNS disorders.

    Science.gov (United States)

    Shan, Ling; Dauvilliers, Yves; Siegel, Jerome M

    2015-07-01

    Histamine and hypocretin neurons are localized to the hypothalamus, a brain area critical to autonomic function and sleep. Narcolepsy type 1, also known as narcolepsy with cataplexy, is a neurological disorder characterized by excessive daytime sleepiness, impaired night-time sleep, cataplexy, sleep paralysis and short latency to rapid eye movement (REM) sleep after sleep onset. In narcolepsy, 90% of hypocretin neurons are lost; in addition, two groups reported in 2014 that the number of histamine neurons is increased by 64% or more in human patients with narcolepsy, suggesting involvement of histamine in the aetiology of this disorder. Here, we review the role of the histamine and hypocretin systems in sleep-wake modulation. Furthermore, we summarize the neuropathological changes to these two systems in narcolepsy and discuss the possibility that narcolepsy-associated histamine abnormalities could mediate or result from the same processes that cause the hypocretin cell loss. We also review the changes in the hypocretin and histamine systems, and the associated sleep disruptions, in Parkinson disease, Alzheimer disease, Huntington disease and Tourette syndrome. Finally, we discuss novel therapeutic approaches for manipulation of the histamine system.

  3. [11C]NS8880, a promising PET radiotracer targeting the norepinephrine transporter

    DEFF Research Database (Denmark)

    Vase, Karina Højrup; Peters, Dan; Nielsen, Elsebeth Ø

    2014-01-01

    -azabicyclo[3.2.1]octane (NS8880), targeting NET. NS8880 has an in vitro binding profile comparable to desipramine and is structurally not related to reboxetine. METHODS: Labeling of NS8880 with [11C] was achieved by a non-conventional technique: substitution of pyridinyl fluorine with [11C]methanolate...... yields with high purity. The PET in vivo evaluation in pig and rat revealed a rapid brain uptake of [11C]NS8880 and fast obtaining of equilibrium. Highest binding was observed in thalamic and hypothalamic regions. Pretreatment with desipramine efficiently reduced binding of [11C]NS8880. CONCLUSION: Based...... on the pre-clinical results obtained so far [11C]NS8880 displays promising properties for PET imaging of NET....

  4. Serial brain MRI findings in CNS involvement of familial erythrophagocytic lymphohistiocytosis: a case report

    International Nuclear Information System (INIS)

    Cho, Kyung Soo; Yoo, Jeong Hyun; Suh, Jeong Soo; Ryu, Kyung Ha; Hong, Ki Sook; Kim, Hak Jin

    2002-01-01

    Familial erythrophagocytic lymphohistiocytosis is a fatal early childhood disorder characterized by multiorgan lymphohistiocytic infiltration and active hemophagocytosis. Involvement of the central nervous system (CNS) is not uncommon and is characterized by rapidly progressive tissue damage affecting both the gray and white matter. We encountered a case of familial erythrophagocytic lymphohistiocytosis with CNS involvement. Initial T2-weighted MRI of the brain demonstrated high signal intensity in the right thalamus, though after chemotherapy, which led to the relief of neurologic symptoms, this disappeared. After four months. however, the patient's neurologic symptoms recurred, and follow-up T2-weighted MR images showed high signal intensity in the thalami, basal ganglia, and cerebral and cerebellar white matter. Brain MRI is a useful imaging modality for the evaluation of CNS involvement and monitoring the response to treatment

  5. Analysis of neurocognitive function and CNS endpoints in the PROTEA trial

    DEFF Research Database (Denmark)

    Clarke, Amanda; Johanssen, Veronika; Gerstoft, Jan

    2014-01-01

    INTRODUCTION: During treatment with protease inhibitor monotherapy, the number of antiretrovirals with therapeutic concentrations in the cerebrospinal fluid (CSF) is lower, compared to standard triple therapy. However, the clinical consequences are unclear. METHODS: A total of 273 patients with HIV...... and the Grooved Pegboard Test at screening, baseline and at Week 48. A global neurocognitive score (NPZ-5) was derived by averaging the standardized results of the five domains. In a central nervous system (CNS) sub-study (n=70), HIV RNA levels in the CNS were evaluated at baseline and Week 48. Clinical adverse...... events related to the CNS were collected at each visit. RESULTS: Patients were 83% male and 88% White, with median age 43 years. There were more patients with nadir CD4 count below 200 cells/µL in the DRV/r monotherapy arm (41/137, 30%) than the triple therapy arm (30/136, 22%). At Week 48...

  6. Intellectual abilities among survivors of childhood leukaemia as a function of CNS irradiation

    International Nuclear Information System (INIS)

    Eiser, C.

    1978-01-01

    Twenty-eight children in remission at least 2 years after completing chemotherapy for acute lymphoblastic leukaemia were assessed on standardised psychological tests. It was found that 7 who never had central nervous system (CNS) irradiation and 9 having prophylactic CNS irradiation at least 6 months after diagnosis tended to perform at average or above levels, while those 10 each having prophylactic CNS irradiation (within 2 months of diagnosis) were generally at lower ability. Within the latter group 3 children showed serious intellectual impairments, while the group as a whole functioned especially poorly on quantitative tasks and those involving speeded performance with abstract material. General language ability was not affected. Practical and theoretical implications are discussed. (author)

  7. Cancers of the Brain and CNS: Global Patterns and Trends in Incidence.

    Science.gov (United States)

    Mortazavi, S M J; Mortazavi, S A R; Paknahad, M

    2018-03-01

    Miranda-Filho et al. in their recently published paper entitled "Cancers of the brain and CNS: global patterns and trends in incidence" provided a global status report of the geographic and temporal variations in the incidence of brain and CNS cancers in different countries across continents worldwide. While the authors confirm the role of genetic risk factors and ionizing radiation exposures, they claimed that no firm conclusion could be drawn about the role of exposure to non-ionizing radiation. The paper authored by Miranda-Filho et al. not only addresses a challenging issue, it can be considered as a good contribution in the field of brain and CNS cancers. However, our correspondence addresses a basic shortcoming of this paper about the role of electromagnetic fields and cancers and provides evidence showing that exposure to radiofrequency electromagnetic fields (RF-EMFs), at least at high levels and long durations, can increases the risk of cancer.

  8. Neonatal CNS infection and inflammation caused by Ureaplasma species: rare or relevant?

    Science.gov (United States)

    Glaser, Kirsten; Speer, Christian P

    2015-02-01

    Colonization with Ureaplasma species has been associated with adverse pregnancy outcome, and perinatal transmission has been implicated in the development of bronchopulmonary dysplasia in preterm neonates. Little is known about Ureaplasma-mediated infection and inflammation of the CNS in neonates. Controversy remains concerning its incidence and implication in the pathogenesis of neonatal brain injury. In vivo and in vitro data are limited. Despite improving care options for extremely immature preterm infants, relevant complications remain. Systematic knowledge of ureaplasmal infection may be of great benefit. This review aims to summarize pathogenic mechanisms, clinical data and diagnostic pitfalls. Studies in preterm and term neonates are critically discussed with regard to their limitations. Clinical questions concerning therapy or prophylaxis are posed. We conclude that ureaplasmas may be true pathogens, especially in preterm neonates, and may cause CNS inflammation in a complex interplay of host susceptibility, serovar pathogenicity and gestational age-dependent CNS vulnerability.

  9. Targeted exome sequencing integrated with clinicopathological information reveals novel and rare mutations in atypical, suspected and unknown cases of Alport syndrome or proteinuria.

    Directory of Open Access Journals (Sweden)

    Rajshekhar Chatterjee

    Full Text Available We applied customized targeted next-generation exome sequencing (NGS to determine if mutations in genes associated with renal malformations, Alport syndrome (AS or nephrotic syndrome are a potential cause of renal abnormalities in patients with equivocal or atypical presentation. We first sequenced 4,041 exons representing 292 kidney disease genes in a Caucasian woman with a history of congenital vesicoureteral reflux (VUR, recurrent urinary tract infections and hydronephrosis who presented with nephrotic range proteinuria at the age of 45. Her biopsy was remarkable for focal segmental glomerulosclerosis (FSGS, a potential complication of longstanding VUR. She had no family history of renal disease. Her proteinuria improved initially, however, several years later she presented with worsening proteinuria and microhematuria. NGS analysis revealed two deleterious COL4A3 mutations, one novel and the other previously reported in AS, and a novel deleterious SALL2 mutation, a gene linked to renal malformations. Pedigree analysis confirmed that COL4A3 mutations were nonallelic and compound heterozygous. The genomic results in conjunction with subsequent abnormal electron microscopy, Collagen IV minor chain immunohistochemistry and progressive sensorineural hearing loss confirmed AS. We then modified our NGS approach to enable more efficient discovery of variants associated with AS or a subset of FSGS by multiplexing targeted exome sequencing of 19 genes associated with AS or FSGS in 14 patients. Using this approach, we found novel or known COL4A3 or COL4A5 mutations in a subset of patients with clinically diagnosed or suspected AS, APOL1 variants associated with FSGS in African Americans and novel mutations in genes associated with nephrotic syndrome. These studies demonstrate the successful application of targeted capture-based exome sequencing to simultaneously evaluate genetic variations in many genes in patients with complex renal phenotypes and

  10. Clearance of an immunosuppressive virus from the CNS coincides with immune reanimation and diversification

    Directory of Open Access Journals (Sweden)

    McGavern Dorian B

    2007-06-01

    Full Text Available Abstract Once a virus infection establishes persistence in the central nervous system (CNS, it is especially difficult to eliminate from this specialized compartment. Therefore, it is of the utmost importance to fully understand scenarios during which a persisting virus is ultimately purged from the CNS by the adaptive immune system. Such a scenario can be found following infection of adult mice with an immunosuppressive variant of lymphocytic choriomeningitis virus (LCMV referred to as clone 13. In this study we demonstrate that following intravenous inoculation, clone 13 rapidly infected peripheral tissues within one week, but more slowly inundated the entire brain parenchyma over the course of a month. During the establishment of persistence, we observed that genetically tagged LCMV-specific cytotoxic T lymphocytes (CTL progressively lost function; however, the severity of this loss in the CNS was never as substantial as that observed in the periphery. One of the most impressive features of this model system is that the peripheral T cell response eventually regains functionality at ~60–80 days post-infection, and this was associated with a rapid decline in virus from the periphery. Coincident with this "reanimation phase" was a massive influx of CD4 T and B cells into the CNS and a dramatic reduction in viral distribution. In fact, olfactory bulb neurons served as the last refuge for the persisting virus, which was ultimately purged from the CNS within 200 days post-infection. These data indicate that a functionally revived immune response can prevail over a virus that establishes widespread presence both in the periphery and brain parenchyma, and that therapeutic enhancement of an existing response could serve as an effective means to thwart long term CNS persistence.

  11. CD11c-expressing cells affect Treg behavior in the meninges during CNS infection1

    Science.gov (United States)

    O’Brien, Carleigh A.; Overall, Christopher; Konradt, Christoph; O’Hara Hall, Aisling C.; Hayes, Nikolas W.; Wagage, Sagie; John, Beena; Christian, David A.; Hunter, Christopher A.; Harris, Tajie H.

    2017-01-01

    Treg cells play an important role in the CNS during multiple infections as well as autoimmune inflammation, but the behavior of this cell type in the CNS has not been explored. In mice, infection with Toxoplasma gondii leads to a Th1-polarized parasite-specific effector T cell response in the brain. Similarly, the Treg cells in the CNS during T. gondii infection are Th1-polarized, exemplified by T-bet, CXCR3, and IFN-γ expression. Unlike effector CD4+ T cells, an MHC Class II tetramer reagent specific for T. gondii did not recognize Treg cells isolated from the CNS. Likewise, TCR sequencing revealed minimal overlap in TCR sequence between effector and regulatory T cells in the CNS. Whereas effector T cells are found in the brain parenchyma where parasites are present, Treg cells were restricted to the meninges and perivascular spaces. The use of intravital imaging revealed that activated CD4+ T cells within the meninges were highly migratory, while Treg cells moved more slowly and were found in close association with CD11c+ cells. To test whether the behavior of Tregs in the meninges is influenced by interactions with CD11c+ cells, mice were treated with anti-LFA-1 antibodies to reduce the number of CD11c+ cells in this space. The anti-LFA-1 treatment led to fewer contacts between Tregs and the remaining CD11c+ cells and increased the speed of Treg cell migration. These data suggest that Treg cells are anatomically restricted within the CNS and the interaction with CD11c+ populations regulates their local behavior during T. gondii infection. PMID:28389591

  12. Hypocomplementemic Urticarial Vasculitis Syndrome With Crescentic Glomerulonephritis.

    Science.gov (United States)

    Salim, Sohail Abdul; Yousuf, Tauqeer; Patel, Asha; Fülöp, Tibor; Agarwal, Mohit

    2018-02-01

    Hypocomplementemic urticarial vasculitis syndrome (HUVS) is a rare autoimmune disease characterized by multiple organ system involvement, including renal disease, with low complement levels. We report the case of a 31-year-old woman who presented with nonspecific symptoms including fatigue, diarrhea, macular rash and abdominal pain with acute renal failure leading to end-stage kidney disease. Laboratory results showed hematuria, nephrotic range proteinuria, worsening creatinine and low C1q levels. Left kidney biopsy showed proliferative glomerulonephritis with crescent formation. She was treated with 6 months of intravenous cyclophosphamide, followed by 2 doses of intravenous rituximab (1g each), thereafter maintained on mycophenolate mofetil and glucocorticoid-based therapy. She experienced a full recovery of renal function after 12 months of dialysis dependence. Hypocomplementemic urticarial vasculitis syndrome with crescentic glomerulonephritis is a rare disease with only 5 other reported cases in literature. In our case, we document a delayed but excellent renal recovery during a 2-year follow-up. Copyright © 2018 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.

  13. Kinetic modelling of [123I]CNS 1261--a potential SPET tracer for the NMDA receptor

    International Nuclear Information System (INIS)

    Erlandsson, Kjell; Bressan, Rodrigo A.; Mulligan, Rachel S.; Gunn, Roger N; Cunningham, Vincent J.; Owens, Jonathan; Wyper, David; Ell, Peter J.; Pilowsky, Lyn S.

    2003-01-01

    N-(1-napthyl)-N'-(3-[ 123 I]-iodophenyl)-N-methylguanidine ([ 123 I]CNS 1261) is a novel SPET ligand developed for imaging the NMDA receptor intra-channel MK 801/PCP/ketamine site. Data was acquired in 7 healthy volunteers after bolus injection of [ 123 I]CNS 1261. Kinetic modeling showed reversible tracer binding. Arterial and venous time-activity curves overlapped after 90 min. The rank order of binding was: Thalamus > striatum > cortical regions > white matter. This distribution concurs with [ 11 C]-ketamine and [ 18 F]-memantine PET studies . These data provide a methodological basis for further direct in vivo challenge studies

  14. Effects of x rays on the morphology and physiology of the CNS blood vessels of mice

    Energy Technology Data Exchange (ETDEWEB)

    Gladysz, J [Akademia Medyczna, Poznan (Poland)

    1974-01-01

    Irradiation of the CNS of mice with 4000 to 7600 R produces transitional disorder of the permeability of vascular walls, followed by a permanent (irreversible) degenerative lesion of blood capillaries and the surrounding astrogial cells. Intensity of this alterations may however not be the same in different terminal blood vessels. It is very likely that the above described lesion appearing in the acute phase can be the main cause of further alterations in the CNS which are observed in late phase of postradiation disease.

  15. Lentiviral-mediated administration of IL-25 in the CNS induces alternative activation of microglia

    DEFF Research Database (Denmark)

    Maiorino, C; Khorooshi, R; Ruffini, F

    2013-01-01

    Interleukin-25 (IL-25) is the only anti-inflammatory cytokine of the IL-17 family, and it has been shown to be efficacious in inhibiting neuroinflammation. Known for its effects on cells of the adaptive immune system, it has been more recently described to be effective also on cells of the innate...... was partly inhibited and the CNS protected from immune-mediated damage. To our knowledge, this is the first example of M2 shift (alternative activation) induced in vivo on CNS-resident myeloid cells by gene therapy, and may constitute a promising strategy to investigate the potential role of protective...

  16. Metallothionein-1+2 protect the CNS after a focal brain injury

    DEFF Research Database (Denmark)

    Giralt, Mercedes; Penkowa, Milena; Lago, Natalia

    2002-01-01

    We have evaluated the physiological relevance of metallothionein-1+2 (MT-1+2) in the CNS following damage caused by a focal cryolesion onto the cortex. In comparison to normal mice, transgenic mice overexpressing the MT-1 isoform (TgMTI* mice) showed a significant decrease of the number...... dramatically reduced the cryolesion-induced oxidative stress and neuronal apoptosis. Remarkably, these effects were also obtained by the intraperitoneal administration of MT-2 to both normal and MT-1+2 knock-out mice. These results fully support the notion that MT-1+2 are essential in the CNS for coping...

  17. Imaging aspects of neurologic emergencies in children treated for non-CNS malignancies

    International Nuclear Information System (INIS)

    Kaste, S.C.; Langston, J.; Rodriguez-Galindo, C.; Furman, W.L.; Thompson, S.J.

    2000-01-01

    There is a paucity of radiologic literature addressing neurologic emergencies in children receiving therapy for non-CNS primary malignancies. In the acute setting, many of these children present to local community hospitals. This pictorial is from a single institutional experience describing the spectrum of neurologic emergencies seen in children with non-CNS cancers. We hope to familiarize pediatric radiologists with these entities in order to expedite diagnosis, facilitate treatment, and minimize morbity and mortality that may be associated with these complications. (orig.)

  18. Neuroprotective effects of estrogen in CNS injuries: insights from animal models

    Directory of Open Access Journals (Sweden)

    Raghava N

    2017-07-01

    Full Text Available Narayan Raghava,1 Bhaskar C Das,2 Swapan K Ray1 1Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA; 2Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA Abstract: Among the estrogens that are biosynthesized in the human body, 17β-estradiol (estradiol or E2 is the most common and the best estrogen for neuroprotection in animal models of the central nervous system (CNS injuries such as spinal cord injury (SCI, traumatic brain injury (TBI, and ischemic brain injury (IBI. These CNS injuries are not only serious health problems, but also enormous economic burden on the patients, their families, and the society at large. Studies from animal models of these CNS injuries provide insights into the multiple neuroprotective mechanisms of E2 and also suggest the possibility of translating the therapeutic efficacy of E2 in the treatment SCI, TBI, and IBI in humans in the near future. The pathophysiology of these injuries includes loss of motor function in the limbs, arms and their extremities, cognitive deficit, and many other serious consequences including life-threatening paralysis, infection, and even death. The potential application of E2 therapy to treat the CNS injuries may become a trend as the results are showing significant therapeutic benefits of E2 for neuroprotection when administered into the animal models of SCI, TBI, and IBI. This article describes the plausible mechanisms how E2 works with or without the involvement of estrogen receptors and provides an overview of the known neuroprotective effects of E2 in these three CNS injuries in different animal models. Because activation of estrogen receptors has profound implications in maintaining and also affecting normal physiology, there are notable impediments in translating E2 therapy to the clinics for neuroprotection in CNS injuries in humans. While E2 may not yet be the sole molecule for

  19. Hamartomatous polyposis syndromes

    DEFF Research Database (Denmark)

    Jelsig, Anne Marie; Qvist, Niels; Brusgaard, Klaus

    2014-01-01

    Hamartomatous Polyposis Syndromes (HPS) are genetic syndromes, which include Peutz-Jeghers syndrome, Juvenile polyposis syndrome, PTEN hamartoma tumour syndrome (Cowden Syndrom, Bannayan-Riley-Ruvalcaba and Proteus Syndrome) as well as hereditary mixed polyposis syndrome. Other syndromes such as ......Hamartomatous Polyposis Syndromes (HPS) are genetic syndromes, which include Peutz-Jeghers syndrome, Juvenile polyposis syndrome, PTEN hamartoma tumour syndrome (Cowden Syndrom, Bannayan-Riley-Ruvalcaba and Proteus Syndrome) as well as hereditary mixed polyposis syndrome. Other syndromes...

  20. Is risk of central nervous system (CNS) relapse related to adjuvant taxane treatment in node-positive breast cancer? Results of the CNS substudy in the intergroup Phase III BIG 02-98 Trial

    DEFF Research Database (Denmark)

    Pestalozzi, B.C.; Francis, P.; Quinaux, E.

    2008-01-01

    BACKGROUND: Breast cancer central nervous system (CNS) metastases are an increasingly important problem because of high CNS relapse rates in patients treated with trastuzumab and/or taxanes. PATIENTS AND METHODS: We evaluated data from 2887 node-positive breast cancer patients randomised in the BIG...

  1. Intraoperative squash smear cytology in CNS lesions: A study of 150 pediatric cases

    Directory of Open Access Journals (Sweden)

    Arpita Jindal

    2017-01-01

    Full Text Available Background: Tumors of the central nervous system in the pediatric age group occur relatively frequently during the early years of life. Brain tumors are the most common solid malignancies of childhood and only second to acute childhood leukemia. Squash cytology is an indispensable diagnostic aid to central nervous system (CNS lesions. The definitive diagnosis of brain lesions is confirmed by histological examination. Aim: To study the cytology of CNS lesions in pediatric population and correlate it with histopathology. Materials and Methods: One hundred and fifty cases of CNS lesions in pediatric patients were studied over a period of 2 years. Intraoperative squash smears were prepared, stained with hematoxylin and eosin, and examined. Remaining sample was subjected to histopathological examination. Results: Medulloblastoma (24.0% was the most frequently encountered tumor followed by pilocyctic astrocytoma (21.33% and ependymoma (13.33%. Diagnostic accuracy of squash smear technique was 94.67% when compared with histological diagnosis. Conclusion: Smear cytology is a fairly accurate tool for intraoperative CNS consultations.

  2. Mining the topography and dynamics of the 4D Nucleome to identify novel CNS drug pathways.

    Science.gov (United States)

    Higgins, Gerald A; Allyn-Feuer, Ari; Georgoff, Patrick; Nikolian, Vahagn; Alam, Hasan B; Athey, Brian D

    2017-07-01

    The pharmacoepigenome can be defined as the active, noncoding province of the genome including canonical spatial and temporal regulatory mechanisms of gene regulation that respond to xenobiotic stimuli. Many psychotropic drugs that have been in clinical use for decades have ill-defined mechanisms of action that are beginning to be resolved as we understand the transcriptional hierarchy and dynamics of the nucleus. In this review, we describe spatial, temporal and biomechanical mechanisms mediated by psychotropic medications. Focus is placed on a bioinformatics pipeline that can be used both for detection of pharmacoepigenomic variants that discretize drug response and adverse events to improve pharmacogenomic testing, and for the discovery of novel CNS therapeutics. This approach integrates the functional topology and dynamics of the transcriptional hierarchy of the pharmacoepigenome, gene variant-driven identification of pharmacogenomic regulatory domains, and mesoscale mapping for the discovery of novel CNS pharmacodynamic pathways in human brain. Examples of the application of this pipeline are provided, including the discovery of valproic acid (VPA) mediated transcriptional reprogramming of neuronal cell fate following injury, and mapping of a CNS pathway glutamatergic pathway for the mood stabilizer lithium. These examples in regulatory pharmacoepigenomics illustrate how ongoing research using the 4D nucleome provides a foundation to further insight into previously unrecognized psychotropic drug pharmacodynamic pathways in the human CNS. Copyright © 2017. Published by Elsevier Inc.

  3. Inflammatory cytokines in the brain: does the CNS shape immune responses?

    DEFF Research Database (Denmark)

    Owens, T; Renno, T; Taupin, V

    1994-01-01

    Immune responses in the central nervous system (CNS) have traditionally been regarded as representing the intrusion of an unruly, ill-behaved mob of leukocytes into the well-ordered and organized domain of thought and reason. However, results accumulated over the past few years suggest that, far ...

  4. A safety assessment methodology applied to CNS/ATM-based air traffic control system

    Energy Technology Data Exchange (ETDEWEB)

    Vismari, Lucio Flavio, E-mail: lucio.vismari@usp.b [Safety Analysis Group (GAS), School of Engineering at University of Sao Paulo (Poli-USP), Av. Prof. Luciano Gualberto, Trav.3, n.158, Predio da Engenharia de Eletricidade, Sala C2-32, CEP 05508-900, Sao Paulo (Brazil); Batista Camargo Junior, Joao, E-mail: joaocamargo@usp.b [Safety Analysis Group (GAS), School of Engineering at University of Sao Paulo (Poli-USP), Av. Prof. Luciano Gualberto, Trav.3, n.158, Predio da Engenharia de Eletricidade, Sala C2-32, CEP 05508-900, Sao Paulo (Brazil)

    2011-07-15

    In the last decades, the air traffic system has been changing to adapt itself to new social demands, mainly the safe growth of worldwide traffic capacity. Those changes are ruled by the Communication, Navigation, Surveillance/Air Traffic Management (CNS/ATM) paradigm , based on digital communication technologies (mainly satellites) as a way of improving communication, surveillance, navigation and air traffic management services. However, CNS/ATM poses new challenges and needs, mainly related to the safety assessment process. In face of these new challenges, and considering the main characteristics of the CNS/ATM, a methodology is proposed at this work by combining 'absolute' and 'relative' safety assessment methods adopted by the International Civil Aviation Organization (ICAO) in ICAO Doc.9689 , using Fluid Stochastic Petri Nets (FSPN) as the modeling formalism, and compares the safety metrics estimated from the simulation of both the proposed (in analysis) and the legacy system models. To demonstrate its usefulness, the proposed methodology was applied to the 'Automatic Dependent Surveillance-Broadcasting' (ADS-B) based air traffic control system. As conclusions, the proposed methodology assured to assess CNS/ATM system safety properties, in which FSPN formalism provides important modeling capabilities, and discrete event simulation allowing the estimation of the desired safety metric.

  5. Durable treatment response of relapsing CNS plasmacytoma using intrathecal chemotherapy, radiotherapy, and Daratumumab.

    Science.gov (United States)

    Elhassadi, Ezzat; Murphy, Maurice; Hacking, Dayle; Farrell, Michael

    2018-04-01

    CNS myelomatous involvement is a rare complication of multiple myeloma with dismal outcome. This disease's optimal treatment is unclear. Combined approach of systemic therapy, radiotherapy, and intrathecal injections chemotherapy should be considered and autologous stem cell transplant consolidation is offered to eligible patients. The role of Daratumumab in this disease deserves further evaluation.

  6. Chemokines in the balance: maintenance of homeostasis and protection at CNS barriers

    Directory of Open Access Journals (Sweden)

    Jessica L Williams

    2014-05-01

    Full Text Available In the adult central nervous system (CNS, chemokines and their receptors are involved in developmental, physiological and pathological processes. Although most lines of investigation focus on their ability to induce the migration of cells, recent studies indicate that chemokines also promote cellular interactions and activate signaling pathways that maintain CNS homeostatic functions. Many homeostatic chemokines are expressed on the vasculature of the blood brain barrier including CXCL12, CCL19, CCL20, and CCL21. While endothelial cell expression of these chemokines is known to regulate the entry of leukocytes into the CNS during immunosurveillance, new data indicate that CXCL12 is also involved in diverse cellular activities including adult neurogenesis and neuronal survival, having an opposing role to the homeostatic chemokine, CXCL14, which appears to regulate synaptic inputs to neural precursors. Neuronal expression of CX3CL1, yet another homeostatic chemokine that promotes neuronal survival and communication with microglia, is partly regulated by CXCL12. Regulation of CXCL12 is unique in that it may regulate its own expression levels via binding to its scavenger receptor CXCR7/ACKR3. In this review, we explore the diverse roles of these and other homeostatic chemokines expressed within the CNS, including the possible implications of their dysfunction as a cause of neurologic disease.

  7. Nootropic, anxiolytic and CNS-depressant studies on different plant sources of shankhpushpi.

    Science.gov (United States)

    Malik, Jai; Karan, Maninder; Vasisht, Karan

    2011-12-01

    Shankhpushpi, a well-known drug in Ayurveda, is extensively used for different central nervous system (CNS) effects especially memory enhancement. Different plants are used under the name shankhpushpi in different regions of India, leading to an uncertainty regarding its true source. Plants commonly used under the name shankhpushpi are: Convolvulus pluricaulis Chois., Evolvulus alsinoides Linn., both from Convolvulaceae, and Clitoria ternatea Linn. (Leguminosae). To find out the true source of shankhpushpi by evaluating and comparing memory-enhancing activity of the three above mentioned plants. Anxiolytic, antidepressant and CNS-depressant activities of these three plants were also compared and evaluated. The nootropic activity of the aqueous methanol extract of each plant was tested using elevated plus-maze (EPM) and step-down models. Anxiolytic, antidepressant and CNS-depressant studies were evaluated using EPM, Porsolt?s swim despair and actophotometer models, respectively. C. pluricaulis extract (CPE) at a dose of 100 mg/kg, p.o. showed maximum nootropic and anxiolytic activity (p nootropic, anxiolytic and CNS-depressant activity. The results of memory-enhancing activity suggest C. pluricaulis to be used as true source of shankhpushpi.

  8. Mast Cells and Innate Lymphoid Cells: Underappreciated Players in CNS Autoimmune Demyelinating Disease.

    Science.gov (United States)

    Brown, Melissa A; Weinberg, Rebecca B

    2018-01-01

    Multiple sclerosis (MS) and its mouse model, experimental autoimmune encephalomyelitis, are autoimmune CNS inflammatory diseases. As a result of a breakdown in the relatively impermeable blood-brain barrier (BBB) in affected individuals, myelin-specific CD4 + and CD8 + T cells gain entry into the immune privileged CNS and initiate myelin, oligodendrocyte, and nerve axon destruction. However, despite the absolute requirement for T cells, there is increasing evidence that innate immune cells also play critical amplifying roles in disease pathogenesis. By modulating the character and magnitude of the myelin-reactive T cell response and regulating BBB integrity, innate cells affect both disease initiation and progression. Two classes of innate cells, mast cells and innate lymphoid cells (ILCs), have been best studied in models of allergic and gastrointestinal inflammatory diseases. Yet, there is emerging evidence that these cell types also exert a profound influence in CNS inflammatory disease. Both cell types are residents within the meninges and can be activated early in disease to express a wide variety of disease-modifying cytokines and chemokines. In this review, we discuss how mast cells and ILCs can have either disease-promoting or -protecting effects on MS and other CNS inflammatory diseases and how sex hormones may influence this outcome. These observations suggest that targeting these cells and their unique mediators can be exploited therapeutically.

  9. Immune cell entry to the CNS--a focus for immunoregulation of EAE

    DEFF Research Database (Denmark)

    Owens, T; Tran, E; Hassan-Zahraee, M

    1999-01-01

    -requirement then to prove such a role. The point that emerges is that cytokine production in the CNS parenchyma is itself dependent on the prior infiltration of immune cells, and that without immune cell entry, EAE does not occur. This identifies events at the BBB, and in particular in the perivascular space, as critical...

  10. Migration, fate and in vivo imaging of stem cells in the CNS

    Czech Academy of Sciences Publication Activity Database

    Syková, Eva

    2009-01-01

    Roč. 16, Suppl.3 (2009), s. 4-4 ISSN 1351-5101. [Congress of the European-Federation-of-Neurological-Societies /13./. 12.09.2009-15.09.2009, Florencie] Institutional research plan: CEZ:AV0Z50390703 Keywords : CNS * ESC Subject RIV: FH - Neurology

  11. Comparative analysis of acid sphingomyelinase distribution in the CNS of rats and mice following intracerebroventricular delivery.

    Directory of Open Access Journals (Sweden)

    Christopher M Treleaven

    Full Text Available Niemann-Pick A (NPA disease is a lysosomal storage disorder (LSD caused by a deficiency in acid sphingomyelinase (ASM activity. Previously, we reported that biochemical and functional abnormalities observed in ASM knockout (ASMKO mice could be partially alleviated by intracerebroventricular (ICV infusion of hASM. We now show that this route of delivery also results in widespread enzyme distribution throughout the rat brain and spinal cord. However, enzyme diffusion into CNS parenchyma did not occur in a linear dose-dependent fashion. Moreover, although the levels of hASM detected in the rat CNS were determined to be within the range shown to be therapeutic in ASMKO mice, the absolute amounts represented less than 1% of the total dose administered. Finally, our results also showed that similar levels of enzyme distribution are achieved across rodent species when the dose is normalized to CNS weight as opposed to whole body weight. Collectively, these data suggest that the efficacy observed following ICV delivery of hASM in ASMKO mice could be scaled to CNS of the rat.

  12. CNS Damage Classification in Newborn Infants by Neural Network Based Cry Analysis

    NARCIS (Netherlands)

    Poel, Mannes; Ekkel, T.

    2002-01-01

    The central nervous system (CNS) of the human body is the whole system of brain, spinal marrow and nerve cells throughout the body that correlates and regulates the internal reactions of the body and controls its adjustment to the environment. It controls muscles and processes sensory information

  13. CSF Hypocretin-1 Levels and Clinical Profiles in Narcolepsy and Idiopathic CNS Hypersomnia in Norway

    Science.gov (United States)

    Heier, Mona Skard; Evsiukova, Tatiana; Vilming, Steinar; Gjerstad, Michaela D.; Schrader, Harald; Gautvik, Kaare

    2007-01-01

    Objective: To evaluate the relationship between CSF hypocretin-1 levels and clinical profiles in narcolepsy and CNS hypersomnia in Norwegian patients. Method: CSF hypocretin-1 was measured by a sensitive radioimmunoassay in 47 patients with narcolepsy with cataplexy, 7 with narcolepsy without cataplexy, 10 with idiopathic CNS hypersomnia, and a control group. Results: Low hypocretin-1 values were found in 72% of the HLA DQB1*0602 positive patients with narcolepsy and cataplexy. Patients with low CSF hypocretin-1 levels reported more extensive muscular involvement during cataplectic attacks than patients with normal levels. Hypnagogic hallucinations and sleep paralysis occurred more frequently in patients with cataplexy than in the other patient groups, but with no correlation to hypocretin-1 levels. Conclusion: About three quarters of the HLA DQB1*0602 positive patients with narcolepsy and cataplexy had low CSF hypocretin-1 values, and appear to form a distinct clinical entity. Narcolepsy without cataplexy could not be distinguished from idiopathic CNS hypersomnia by clinical symptoms or biochemical findings. Citation: Heier MS; Evsiukova T; Vilming S; Gjerstad MD; Schrader H; Gautvik K. CSF hypocretin-1 levels and clinical profiles in narcolepsy and idiopathic CNS hypersomnia in norway. SLEEP 2007;30(8):969-973. PMID:17702265

  14. A safety assessment methodology applied to CNS/ATM-based air traffic control system

    International Nuclear Information System (INIS)

    Vismari, Lucio Flavio; Batista Camargo Junior, Joao

    2011-01-01

    In the last decades, the air traffic system has been changing to adapt itself to new social demands, mainly the safe growth of worldwide traffic capacity. Those changes are ruled by the Communication, Navigation, Surveillance/Air Traffic Management (CNS/ATM) paradigm , based on digital communication technologies (mainly satellites) as a way of improving communication, surveillance, navigation and air traffic management services. However, CNS/ATM poses new challenges and needs, mainly related to the safety assessment process. In face of these new challenges, and considering the main characteristics of the CNS/ATM, a methodology is proposed at this work by combining 'absolute' and 'relative' safety assessment methods adopted by the International Civil Aviation Organization (ICAO) in ICAO Doc.9689 , using Fluid Stochastic Petri Nets (FSPN) as the modeling formalism, and compares the safety metrics estimated from the simulation of both the proposed (in analysis) and the legacy system models. To demonstrate its usefulness, the proposed methodology was applied to the 'Automatic Dependent Surveillance-Broadcasting' (ADS-B) based air traffic control system. As conclusions, the proposed methodology assured to assess CNS/ATM system safety properties, in which FSPN formalism provides important modeling capabilities, and discrete event simulation allowing the estimation of the desired safety metric.

  15. Diagnostic value of kinetic analysis using dynamic FDG PET in immunocompetent patients with primary CNS lymphoma

    International Nuclear Information System (INIS)

    Nishiyama, Yoshihiro; Yamamoto, Yuka; Monden, Toshihide; Sasakawa, Yasuhiro; Satoh, Katashi; Ohkawa, Motoomi; Kawai, Nobuyuki

    2007-01-01

    The purpose of this study was to investigate the accumulation of FDG in immunocompetent patients with primary central nervous system (CNS) lymphoma using qualitative and quantitative PET images and to compare baseline with follow-up PET after therapy. Twelve immunocompetent patients with CNS lymphoma were examined. Dynamic emission data were acquired for 60 min immediately following injection of FDG. In seven patients, repeated PET studies were performed after treatment. Applying a three-compartment five-parameter model, K 1 , k 2 , k 3 , k 4 , vascular fraction (V B ) and cerebral metabolic rate of glucose (CMR Glc ) were obtained. We evaluated the FDG uptake visually using qualitative and parametric images and quantitatively using parametric images. A total of 12 lesions were identified in ten patients with newly diagnosed CNS lymphoma. On visual analysis, ten lesions showed an increase on qualitative images, eight showed an increase on K 1 images, 12 showed an increase on k 3 images and ten showed an increase on CMR Glc images. On quantitative analysis, k 2 , k 3 and CMR Glc values of the lesion were significantly different from those of the normal grey matter (p 3 and CMR Glc images. The K 1 , k 2 , k 3 and CMR Glc values after treatment were significantly different from those obtained before treatment (p 3 , using dynamic FDG PET might be helpful for diagnosis of CNS lymphoma and for monitoring therapeutic assessment. (orig.)

  16. Chemokine expression by glial cells directs leukocytes to sites of axonal injury in the CNS

    DEFF Research Database (Denmark)

    Babcock, Alicia A; Kuziel, William A; Rivest, Serge

    2003-01-01

    Innate responses in the CNS are critical to first line defense against infection and injury. Leukocytes migrate to inflammatory sites in response to chemokines. We studied leukocyte migration and glial chemokine expression within the denervated hippocampus in response to axonal injury caused by e...

  17. Enhancing Psychosocial Outcomes for Young Adult Childhood CNS Cancer Survivors: Importance of Addressing Vocational Identity and Community Integration

    Science.gov (United States)

    Strauser, David R.; Wagner, Stacia; Wong, Alex W. K.

    2012-01-01

    The purpose of this study was to examine the relationship between vocational identity, community integration, positive and negative affect, and satisfaction with life in a group of young adult central nervous system (CNS) cancer survivors. Participants in this study included 45 young adult CNS cancer survivors who ranged in age from 18 to 30 years…

  18. Distribution of CNS Species on Teat Skin and in Milk Samples from Dairy Cows in Automatic Milking Systems

    DEFF Research Database (Denmark)

    Mahmmod, Yasser; Svennesen, Line; Pedersen, Karl

    identified in milk samples. Staphylococcus chromogenes was detected in both milk (n= 2) and teat skin (n= 1) samples. Data collection will be finished in April 2017. The final results will give new insights into herd specific CNS species patterns and the microbial ecology and epidemiology of common CNS...

  19. Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

    Energy Technology Data Exchange (ETDEWEB)

    Vuillemenot, Brian R., E-mail: bvuillemenot@bmrn.com [BioMarin Pharmaceutical Inc., Novato, CA (United States); Kennedy, Derek [BioMarin Pharmaceutical Inc., Novato, CA (United States); Reed, Randall P.; Boyd, Robert B. [Northern Biomedical Research, Inc., Muskegon, MI (United States); Butt, Mark T. [Tox Path Specialists, LLC, Hagerstown, MD (United States); Musson, Donald G.; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S.; O' Neill, Charles A. [BioMarin Pharmaceutical Inc., Novato, CA (United States)

    2014-05-15

    CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered

  20. Recombinant human tripeptidyl peptidase-1 infusion to the monkey CNS: Safety, pharmacokinetics, and distribution

    International Nuclear Information System (INIS)

    Vuillemenot, Brian R.; Kennedy, Derek; Reed, Randall P.; Boyd, Robert B.; Butt, Mark T.; Musson, Donald G.; Keve, Steve; Cahayag, Rhea; Tsuruda, Laurie S.; O'Neill, Charles A.

    2014-01-01

    CLN2 disease is caused by deficiency in tripeptidyl peptidase-1 (TPP1), leading to neurodegeneration and death. The safety, pharmacokinetics (PK), and CNS distribution of recombinant human TPP1 (rhTPP1) were characterized following a single intracerebroventricular (ICV) or intrathecal-lumbar (IT-L) infusion to cynomolgus monkeys. Animals received 0, 5, 14, or 20 mg rhTPP1, ICV, or 14 mg IT-L, in artificial cerebrospinal fluid (aCSF) vehicle. Plasma and CSF were collected for PK analysis. Necropsies occurred at 3, 7, and 14 days post-infusion. CNS tissues were sampled for rhTPP1 distribution. TPP1 infusion was well tolerated and without effect on clinical observations or ECG. A mild increase in CSF white blood cells (WBCs) was detected transiently after ICV infusion. Isolated histological changes related to catheter placement and infusion were observed in ICV treated animals, including vehicle controls. The CSF and plasma exposure profiles were equivalent between animals that received an ICV or IT-L infusion. TPP1 levels peaked at the end of infusion, at which point the enzyme was present in plasma at 0.3% to 0.5% of CSF levels. TPP1 was detected in brain tissues with half-lives of 3–14 days. CNS distribution between ICV and IT-L administration was similar, although ICV resulted in distribution to deep brain structures including the thalamus, midbrain, and striatum. Direct CNS infusion of rhTPP1 was well tolerated with no drug related safety findings. The favorable nonclinical profile of ICV rhTPP1 supports the treatment of CLN2 by direct administration to the CNS. - Highlights: • TPP1 enzyme replacement therapy to the CNS is in development for CLN2 disease. • Toxicology, pharmacokinetics, and CNS distribution were assessed in monkeys. • TPP1 infusion directly to the brain did not result in any safety concerns. • A positive pharmacokinetic and distribution profile resulted from TPP1 infusion. • This study demonstrates the feasibility of ICV administered

  1. P-glycoprotein trafficking as a therapeutic target to optimize CNS drug delivery.

    Science.gov (United States)

    Davis, Thomas P; Sanchez-Covarubias, Lucy; Tome, Margaret E

    2014-01-01

    The primary function of the blood-brain barrier (BBB)/neurovascular unit is to protect the central nervous system (CNS) from potentially harmful xenobiotic substances and maintain CNS homeostasis. Restricted access to the CNS is maintained via a combination of tight junction proteins as well as a variety of efflux and influx transporters that limits the transcellular and paracellular movement of solutes. Of the transporters identified at the BBB, P-glycoprotein (P-gp) has emerged as the transporter that is the greatest obstacle to effective CNS drug delivery. In this chapter, we provide data to support intracellular protein trafficking of P-gp within cerebral capillary microvessels as a potential target for improved drug delivery. We show that pain-induced changes in P-gp trafficking are associated with changes in P-gp's association with caveolin-1, a key scaffolding/trafficking protein that colocalizes with P-gp at the luminal membrane of brain microvessels. Changes in colocalization with the phosphorylated and nonphosphorylated forms of caveolin-1, by pain, are accompanied by dynamic changes in the distribution, relocalization, and activation of P-gp "pools" between microvascular endothelial cell subcellular compartments. Since redox-sensitive processes may be involved in signaling disassembly of higher-order structures of P-gp, we feel that manipulating redox signaling, via specific protein targeting at the BBB, may protect disulfide bond integrity of P-gp reservoirs and control trafficking to the membrane surface, providing improved CNS drug delivery. The advantage of therapeutic drug "relocalization" of a protein is that the physiological impact can be modified, temporarily or long term, despite pathology-induced changes in gene transcription. © 2014 Elsevier Inc. All rights reserved.

  2. Maternal stress, nutrition and physical activity: Impact on immune function, CNS development and psychopathology.

    Science.gov (United States)

    Marques, Andrea Horvath; Bjørke-Monsen, Anne-Lise; Teixeira, Antônio L; Silverman, Marni N

    2015-08-18

    Evidence suggests that maternal and fetal immune dysfunction may impact fetal brain development and could play a role in neurodevelopmental disorders, although the definitive pathophysiological mechanisms are still not completely understood. Stress, malnutrition and physical inactivity are three maternal behavioral lifestyle factors that can influence immune and central nervous system (CNS) functions in both the mother and fetus, and may therefore, increase risk for neurodevelopmental/psychiatric disorders. First, we will briefly review some aspects of maternal-fetal immune system interactions and development of immune tolerance. Second, we will discuss the bidirectional communication between the immune system and CNS and the pathways by which immune dysfunction could contribute to neurodevelopmental disorders. Third, we will discuss the effects of prenatal stress and malnutrition (over and undernutrition) on perinatal programming of the CNS and immune system, and how this might influence neurodevelopment. Finally, we will discuss the beneficial impact of physical fitness during pregnancy on the maternal-fetal unit and infant and how regular physical activity and exercise can be an effective buffer against stress- and inflammatory-related disorders. Although regular physical activity has been shown to promote neuroplasticity and an anti-inflammatory state in the adult, there is a paucity of studies evaluating its impact on CNS and immune function during pregnancy. Implementing stress reduction, proper nutrition and ample physical activity during pregnancy and the childbearing period may be an efficient strategy to counteract the impact of maternal stress and malnutrition/obesity on the developing fetus. Such behavioral interventions could have an impact on early development of the CNS and immune system and contribute to the prevention of neurodevelopmental and psychiatric disorders. Further research is needed to elucidate this relationship and the underlying

  3. Discrimination of different brain metastases and primary CNS lymphomas using morphologic criteria and diffusion tensor imaging

    Energy Technology Data Exchange (ETDEWEB)

    Bette, S.; Wiestler, B.; Huber, T.; Boeckh-Behrens, T.; Zimmer, C.; Kirschke, J. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neuroradiology; Delbridge, C. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neuropathology; Meyer, B.; Gempt, J. [Technical University Munich, Klinikum rechts der Isar (Germany). Dept. of Neurosurgery

    2016-12-15

    Brain metastases are a common complication of cancer and occur in about 15-40% of patients with malignancies. The aim of this retrospective study was to differentiate between metastases from different primary tumors/CNS lymphyomas using morphologic criteria, fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Morphologic criteria such as hemorrhage, cysts, pattern of contrast enhancement and location were reported in 200 consecutive patients with brain metastases/primary CNS lymphomas. FA and ADC values were measured in regions of interest (ROIs) placed in the contrast-enhancing tumor part, the necrosis and the non-enhancing peritumoral region (NEPTR). Differences between histopathological subtypes of metastases were analyzed using non-parametric tests, decision trees and hierarchical clustering analysis. Significant differences were found in morphologic criteria such as hemorrhage or pattern of contrast enhancement. In diffusion measurements, significant differences between the different tumor entities were only found in ADC analyzed in the contrast-enhancing tumor part. Among single tumor entities, primary CNS lymphomas showed significantly lower median ADC values in the contrast-enhancing tumor part (ADC{sub lymphoma} 0.92 [0.83-1.07] vs. ADC{sub no} {sub lymphoma} 1.35 [1.10-1.64] P=0.001). Further differentiation between types of metastases was not possible using FA and ADC. There were morphologic differences among the main subtypes of brain metastases/CNS lymphomas. However, due to a high variability of common types of metastases and low specificity, prospective differentiation remained challenging. DTI including FA and ADC was not a reliable tool for differentiation between different histopathological subtypes of brain metastases except for CNS lymphomas showing lower ADC values. Biopsy, surgery and staging remain essential for diagnosis.

  4. SPARC and GluA1-Containing AMPA Receptors Promote Neuronal Health Following CNS Injury

    Directory of Open Access Journals (Sweden)

    Emma V. Jones

    2018-02-01

    Full Text Available The proper formation and maintenance of functional synapses in the central nervous system (CNS requires communication between neurons and astrocytes and the ability of astrocytes to release neuromodulatory molecules. Previously, we described a novel role for the astrocyte-secreted matricellular protein SPARC (Secreted Protein, Acidic and Rich in Cysteine in regulating α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs and plasticity at developing synapses. SPARC is highly expressed by astrocytes and microglia during CNS development but its level is reduced in adulthood. Interestingly, SPARC has been shown to be upregulated in CNS injury and disease. However, the role of SPARC upregulation in these contexts is not fully understood. In this study, we investigated the effect of chronic SPARC administration on glutamate receptors on mature hippocampal neuron cultures and following CNS injury. We found that SPARC treatment increased the number of GluA1-containing AMPARs at synapses and enhanced synaptic function. Furthermore, we determined that the increase in synaptic strength induced by SPARC could be inhibited by Philanthotoxin-433, a blocker of homomeric GluA1-containing AMPARs. We then investigated the effect of SPARC treatment on neuronal health in an injury context where SPARC expression is upregulated. We found that SPARC levels are increased in astrocytes and microglia following middle cerebral artery occlusion (MCAO in vivo and oxygen-glucose deprivation (OGD in vitro. Remarkably, chronic pre-treatment with SPARC prevented OGD-induced loss of synaptic GluA1. Furthermore, SPARC treatment reduced neuronal death through Philanthotoxin-433 sensitive GluA1 receptors. Taken together, this study suggests a novel role for SPARC and GluA1 in promoting neuronal health and recovery following CNS damage.

  5. Alcohol intake alters immune responses and promotes CNS viral persistence in mice.

    Science.gov (United States)

    Loftis, Jennifer M; Taylor, Jonathan; Raué, Hans-Peter; Slifka, Mark K; Huang, Elaine

    2016-10-01

    Chronic hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic effects, including central nervous system (CNS) damage and neuropsychiatric impairments. Alcohol abuse can exacerbate these adverse effects on brain and behavior, but the molecular mechanisms are not well understood. This study investigated the role of alcohol in regulating viral persistence and CNS immunopathology in mice infected with lymphocytic choriomeningitis virus (LCMV), a model for HCV infections in humans. Female and male BALB/c mice (n=94) were exposed to alcohol (ethanol; EtOH) and water (or water only) using a two-bottle choice paradigm, followed one week later by infection with either LCMV clone 13 (causes chronic infection similar to chronic HCV), LCMV Armstrong (causes acute infection), or vehicle. Mice were monitored for 60days post-infection and continued to receive 24-h access to EtOH and water. Animals infected with LCMV clone 13 drank more EtOH, as compared to those with an acute or no viral infection. Six weeks after infection with LCMV clone 13, mice with EtOH exposure evidenced higher serum viral titers, as compared to mice without EtOH exposure. EtOH intake was also associated with reductions in virus-specific CD8(+) T cell frequencies (particularly CD11a(hi) subsets) and evidence of persistent CNS viremia in chronically infected mice. These findings support the hypothesis that EtOH use and chronic viral infection can result in combined toxic effects accelerating CNS damage and neuropsychiatric dysfunction and suggest that examining the role of EtOH in regulating viral persistence and CNS immunopathology in mice infected with LCMV can lead to a more comprehensive understanding of comorbid alcohol use disorder and chronic viral infection. Published by Elsevier B.V.

  6. Ketamine displaces the novel NMDA receptor SPET probe [123I]CNS-1261 in humans in vivo

    International Nuclear Information System (INIS)

    Stone, James M.; Erlandsson, Kjell; Arstad, Erik; Bressan, Rodrigo A.; Squassante, Lisa; Teneggi, Vincenza; Ell, Peter J.; Pilowsky, Lyn S.

    2006-01-01

    [ 123 I]CNS-1261 [N-(1-naphthyl)-N'-(3-iodophenyl)-N-methylguanidine] is a high-affinity SPET ligand with selectivity for the intrachannel PCP/ketamine/MK-801 site of the N-methyl-D-aspartate (NMDA) receptor. This study evaluated the effects of ketamine (a specific competitor for the intrachannel PCP/ketamine/MK-801 site) on [ 123 I]CNS-1261 binding to NMDA receptors in vivo. Ten healthy volunteers underwent 2 bolus-plus-infusion [ 123 I]CNS-1261 scans, one during placebo and the other during a ketamine challenge. Ketamine administration led to a significant decrease in [ 123 I]CNS-1261 V T in most of the brain regions examined (P 123 I]CNS-1261 appears to be a specific ligand in vivo for the intrachannel PCP/ketamine/MK-801 NMDA binding site

  7. Ketamine displaces the novel NMDA receptor SPET probe [{sup 123}I]CNS-1261 in humans in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Stone, James M. [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom)]. E-mail: j.stone@iop.kcl.ac.uk; Erlandsson, Kjell [Institute of Nuclear Medicine, University College London, London, W1N 8AA (United Kingdom); Arstad, Erik [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom); Bressan, Rodrigo A. [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom); Squassante, Lisa [GlaxoSmithKline (GSK), Verona 37135 (Italy); Teneggi, Vincenza [GlaxoSmithKline (GSK), Verona 37135 (Italy); Ell, Peter J. [Institute of Nuclear Medicine, University College London, London, W1N 8AA (United Kingdom); Pilowsky, Lyn S. [Institute of Psychiatry, King' s College London, De Crespigny Park London, SE5 8AF (United Kingdom); Institute of Nuclear Medicine, University College London, London, W1N 8AA (United Kingdom)

    2006-02-15

    [{sup 123}I]CNS-1261 [N-(1-naphthyl)-N'-(3-iodophenyl)-N-methylguanidine] is a high-affinity SPET ligand with selectivity for the intrachannel PCP/ketamine/MK-801 site of the N-methyl-D-aspartate (NMDA) receptor. This study evaluated the effects of ketamine (a specific competitor for the intrachannel PCP/ketamine/MK-801 site) on [{sup 123}I]CNS-1261 binding to NMDA receptors in vivo. Ten healthy volunteers underwent 2 bolus-plus-infusion [{sup 123}I]CNS-1261 scans, one during placebo and the other during a ketamine challenge. Ketamine administration led to a significant decrease in [{sup 123}I]CNS-1261 V {sub T} in most of the brain regions examined (P<.05). [{sup 123}I]CNS-1261 appears to be a specific ligand in vivo for the intrachannel PCP/ketamine/MK-801 NMDA binding site.

  8. Marfan Syndrome

    Science.gov (United States)

    Marfan syndrome is a disorder that affects connective tissue. Connective tissues are proteins that support skin, bones, blood vessels, ... A problem with the fibrillin gene causes Marfan syndrome. Marfan syndrome can be mild to severe, and ...

  9. Aarskog syndrome

    Science.gov (United States)

    Aarskog disease; Aarskog-Scott syndrome; AAS; Faciodigitogenital syndrome; Gaciogenital dysplasia ... Aarskog syndrome is a genetic disorder that is linked to the X chromosome. It affects mainly males, but females ...

  10. Williams syndrome

    Science.gov (United States)

    Williams-Beuren syndrome ... Williams syndrome is caused by not having a copy of several genes. It may be passed down in families. ... history of the condition. However, people with Williams syndrome have a 50% chance of passing the disorder ...

  11. Cushing's Syndrome

    OpenAIRE

    宗, 友厚; 伊藤, 勇; 諏訪, 哲也; 武田, 純; MUNE, Tomoatsu

    2003-01-01

    Sixteen cases of verified Cushing's syndrome, and twelve cases of probable Cushing's syndrome were reviewed and data on them were compared with various reports on Cushing's syndrome in the literature.

  12. Tourette syndrome

    Science.gov (United States)

    Gilles de la Tourette syndrome; Tic disorders - Tourette syndrome ... Tourette syndrome is named for Georges Gilles de la Tourette, who first described this disorder in 1885. The disorder is likely passed down through families. ...

  13. Aquaporin-4 IgG autoimmune syndrome and immunoreactivity associated with thyroid cancer

    DEFF Research Database (Denmark)

    Soelberg, Kerstin; Larsen, Stine Rosenkilde; Mørch, Marlene

    2016-01-01

    Tumor cells can express so-called onconeural antigens, which are normally restricted to mature neurons and glial cells in the CNS.1 The detection of neural-reactive immunoglobulin G (IgG) aids the diagnosis of paraneoplastic neurologic syndromes (PNS)1; however, the diagnostic utility and potenti...

  14. Hepatorenal syndrome

    Science.gov (United States)

    ... 2016:chap 153. Nevah MI, Fallon MB. Hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, and other systemic complications of liver disease. In: Feldman M, Friedman LS, Brandt LJ, ...

  15. Dynamic of CSF and serum biomarkers in HIV-1 subtype C encephalitis with CNS genetic compartmentalization-case study.

    Science.gov (United States)

    de Almeida, Sergio M; Rotta, Indianara; Ribeiro, Clea E; Oliveira, Michelli F; Chaillon, Antoine; de Pereira, Ana Paula; Cunha, Ana Paula; Zonta, Marise; Bents, Joao França; Raboni, Sonia M; Smith, Davey; Letendre, Scott; Ellis, Ronald J

    2017-06-01

    Despite the effective suppression of viremia with antiretroviral therapy, HIV can still replicate in the central nervous system (CNS). This was a longitudinal study of the cerebrospinal fluid (CSF) and serum dynamics of several biomarkers related to inflammation, the blood-brain barrier, neuronal injury, and IgG intrathecal synthesis in serial samples of CSF and serum from a patient infected with HIV-1 subtype C with CNS compartmentalization.The phylogenetic analyses of plasma and CSF samples in an acute phase using next-generation sequencing and F-statistics analysis of C2-V3 haplotypes revealed distinct compartmentalized CSF viruses in paired CSF and peripheral blood mononuclear cell samples. The CSF biomarker analysis in this patient showed that symptomatic CSF escape is accompanied by CNS inflammation, high levels of cell and humoral immune biomarkers, CNS barrier dysfunction, and an increase in neuronal injury biomarkers with demyelization. Independent and isolated HIV replication can occur in the CNS, even in HIV-1 subtype C, leading to compartmentalization and development of quasispecies distinct from the peripheral plasma. These immunological aspects of the HIV CNS escape have not been described previously. To our knowledge, this is the first report of CNS HIV escape and compartmentalization in HIV-1 subtype C.

  16. The Extracellular Environment of the CNS: Influence on Plasticity, Sprouting, and Axonal Regeneration after Spinal Cord Injury

    Science.gov (United States)

    Forbes, Lindsey H.

    2018-01-01

    The extracellular environment of the central nervous system (CNS) becomes highly structured and organized as the nervous system matures. The extracellular space of the CNS along with its subdomains plays a crucial role in the function and stability of the CNS. In this review, we have focused on two components of the neuronal extracellular environment, which are important in regulating CNS plasticity including the extracellular matrix (ECM) and myelin. The ECM consists of chondroitin sulfate proteoglycans (CSPGs) and tenascins, which are organized into unique structures called perineuronal nets (PNNs). PNNs associate with the neuronal cell body and proximal dendrites of predominantly parvalbumin-positive interneurons, forming a robust lattice-like structure. These developmentally regulated structures are maintained in the adult CNS and enhance synaptic stability. After injury, however, CSPGs and tenascins contribute to the structure of the inhibitory glial scar, which actively prevents axonal regeneration. Myelin sheaths and mature adult oligodendrocytes, despite their important role in signal conduction in mature CNS axons, contribute to the inhibitory environment existing after injury. As such, unlike the peripheral nervous system, the CNS is unable to revert to a “developmental state” to aid neuronal repair. Modulation of these external factors, however, has been shown to promote growth, regeneration, and functional plasticity after injury. This review will highlight some of the factors that contribute to or prevent plasticity, sprouting, and axonal regeneration after spinal cord injury. PMID:29849554

  17. Anti Ma2-associated myeloradiculopathy: expanding the phenotype of anti-Ma2 associated paraneoplastic syndromes

    OpenAIRE

    Murphy, Sinead M; Khan, Usman; Alifrangis, Constantine; Hazell, Steven; Hrouda, David; Blake, Julian; Ball, Joanna; Gabriel, Carolyn; Markarian, Pierre; Rees, Jeremy; Karim, Abid; Seckl, Michael J; Lunn, Michael P; Reilly, Mary M

    2011-01-01

    Anti-Ma2 associated paraneoplastic syndrome usually presents as limbic encephalitis in association with testicular tumours.1, 2 Only four patients have been reported with involvement outside the CNS, two of whom also had limbic or brainstem encephalitis.2, 3 We report a man with anti- Ma2 associated myeloradiculopathy and previous testicular cancer whose neurological syndrome stabilised and anti-Ma2 titres fell following orchidectomy of a microscopically normal testis.

  18. CNS recruitment of CD8+ T lymphocytes specific for a peripheral virus infection triggers neuropathogenesis during polymicrobial challenge.

    Directory of Open Access Journals (Sweden)

    Christine M Matullo

    2011-12-01

    Full Text Available Although viruses have been implicated in central nervous system (CNS diseases of unknown etiology, including multiple sclerosis and amyotrophic lateral sclerosis, the reproducible identification of viral triggers in such diseases has been largely unsuccessful. Here, we explore the hypothesis that viruses need not replicate in the tissue in which they cause disease; specifically, that a peripheral infection might trigger CNS pathology. To test this idea, we utilized a transgenic mouse model in which we found that immune cells responding to a peripheral infection are recruited to the CNS, where they trigger neurological damage. In this model, mice are infected with both CNS-restricted measles virus (MV and peripherally restricted lymphocytic choriomeningitis virus (LCMV. While infection with either virus alone resulted in no illness, infection with both viruses caused disease in all mice, with ∼50% dying following seizures. Co-infection resulted in a 12-fold increase in the number of CD8+ T cells in the brain as compared to MV infection alone. Tetramer analysis revealed that a substantial proportion (>35% of these infiltrating CD8+ lymphocytes were LCMV-specific, despite no detectable LCMV in CNS tissues. Mechanistically, CNS disease was due to edema, induced in a CD8-dependent but perforin-independent manner, and brain herniation, similar to that observed in mice challenged intracerebrally with LCMV. These results indicate that T cell trafficking can be influenced by other ongoing immune challenges, and that CD8+ T cell recruitment to the brain can trigger CNS disease in the apparent absence of cognate antigen. By extrapolation, human CNS diseases of unknown etiology need not be associated with infection with any particular agent; rather, a condition that compromises and activates the blood-brain barrier and adjacent brain parenchyma can render the CNS susceptible to pathogen-independent immune attack.

  19. Sjögren's syndrome associated with protein losing gastroenteropathy manifested by intestinal lymphangiectasia successfully treated with prednisolone and hydroxychloroquine.

    Science.gov (United States)

    Liao, C-Y; Chien, S-T; Wang, C-C; Chen, I-H; Chiu, H-W; Liu, M-Y; Lin, C-H; Ben, R-J; Tsai, M-K

    2015-12-01

    Protein-losing gastroenteropathy (PLGE), a rare manifestation of primary Sjögren's syndrome (SS), is characterized by profound edema and severe hypoalbuminemia secondary to excessive serum protein loss from the gastrointestinal tract and is clinically indistinguishable from nephrotic syndrome. We report a case of a 30-year-old Taiwanese woman with PLGE-associated SS. In addition to a positive Schirmer's test, she had eye-dryness, thirst, and high levels of anti-SSA antibodies, fulfilling SS criteria. PLGE diagnosis was highly appropriate given the clinical profile of hypoalbuminemia, hypercholesterolemia, pleural effusion, and ascites, with absent cardiac, hepatic, or renal disease. We were unable to perform technetium-99 m-labeled human serum albumin scintigraphy ((99m)Tc-HAS). However, the patient's edema and albumin level improved dramatically in response to a 3-month regime of oral prednisolone followed by oral hydroxychloroquine. © The Author(s) 2015.

  20. Organotypic Cultures as a Model to Study Adult Neurogenesis in CNS Disorders

    Directory of Open Access Journals (Sweden)

    Fabio Cavaliere

    2016-01-01

    Full Text Available Neural regeneration resides in certain specific regions of adult CNS. Adult neurogenesis occurs throughout life, especially from the subgranular zone of hippocampus and the subventricular zone, and can be modulated in physiological and pathological conditions. Numerous techniques and animal models have been developed to demonstrate and observe neural regeneration but, in order to study the molecular and cellular mechanisms and to characterize multiple types of cell populations involved in the activation of neurogenesis and gliogenesis, investigators have to turn to in vitro models. Organotypic cultures best recapitulate the 3D organization of the CNS and can be explored taking advantage of many techniques. Here, we review the use of organotypic cultures as a reliable and well defined method to study the mechanisms of neurogenesis under normal and pathological conditions. As an example, we will focus on the possibilities these cultures offer to study the pathophysiology of diseases like Alzheimer disease, Parkinson’s disease, and cerebral ischemia.

  1. Inflammatory cytokines in the brain: does the CNS shape immune responses?

    Science.gov (United States)

    Owens, T; Renno, T; Taupin, V; Krakowski, M

    1994-12-01

    Immune responses in the central nervous system (CNS) have traditionally been regarded as representing the intrusion of an unruly, ill-behaved mob of leukocytes into the well-ordered and organized domain of thought and reason. However, results accumulated over the past few years suggest that, far from being an immunologically privileged organ, T lymphocytes may be regular and frequent visitors to the CNS, for purposes of immune surveillance. Here, Trevor Owens and colleagues propose that the brain itself can regulate or shape immune responses therein. Furthermore, given that the immune cells may be subverted to autoimmunity, they suggest that the study of inflammatory autoimmune disease in the brain may shed light on the ability of the local environment to regulate immune responses.

  2. Peroxisome Proliferator-Activated Receptors (PPARs as Potential Inducers of Antineoplastic Effects in CNS Tumors

    Directory of Open Access Journals (Sweden)

    Lars Tatenhorst

    2008-01-01

    Full Text Available The peroxisome proliferator-activated receptors (PPARs are ligand-inducible transcription factors which belong to the superfamily of nuclear hormone receptors. In recent years it turned out that natural as well as synthetic PPAR agonists exhibit profound antineoplastic as well as redifferentiation effects in tumors of the central nervous system (CNS. The molecular understanding of the underlying mechanisms is still emerging, with partially controverse findings reported by a number of studies dealing with the influence of PPARs on treatment of tumor cells in vitro. Remarkably, studies examining the effects of these drugs in vivo are just beginning to emerge. However, the agonists of PPARs, in particular the thiazolidinediones, seem to be promising candidates for new approaches in human CNS tumor therapy.

  3. The glymphatic system in CNS health and disease: past, present and future

    Science.gov (United States)

    Plog, Benjamin A.; Nedergaard, Maiken

    2018-01-01

    The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudo-lymphatic function in the brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters brain via periarterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4, and then drives the perivenous drainage of interstitial fluid (ISF) and its solute. Here we review the role of the glymphatic pathway in CNS physiology, factors known to regulate glymphatic flow, and pathologic processes where a breakdown of glymphatic CSF-ISF exchange has been implicated in disease initiation and progression. Important areas of future research, including manipulation of glymphatic activity aiming to improve waste clearance and therapeutic agent delivery, will also be discussed. PMID:29195051

  4. Commercial viability of CNS drugs: balancing the risk/reward profile.

    Science.gov (United States)

    Johnson, Ginger S

    2014-01-01

    CNS has historically been a formidable therapeutic area in which to innovate owing to biological (e.g., complex neurobiology, difficulty reaching the target), as well as clinical (e.g., subjective clinical endpoints, high placebo response, lack of biomarkers) challenges. In the current market where many of the larger diseases are dominated by a generic standard of care, commercial challenges now make the triple threat of scientific-clinical-commercial risk too much for many players to tackle. However, opportunities do exist for smaller biotech companies to concentrate on narrowly focused patient populations associated with high unmet need for which risk can be tightly defined. In CNS, there are two major areas to balance the risk/reward profile and create commercially viable opportunities: To realize value, all companies (start-ups and big players) must define, measure and quantify clear and meaningful value to all stakeholders: physicians, patients, caregivers and payers. © 2013.

  5. Evaluation of CNS activities of aerial parts of Cynodon dactylon Pers. in mice.

    Science.gov (United States)

    Pal, Dilipkumar

    2008-01-01

    The dried extracts of aerial parts of Cynodon dactylon Pers. (Graminae) were evaluated for CNS activities in mice. The ethanol extract of aerial parts of C. dactylon (EECD) was found to cause significant depression in general behavioral profiles in mice. EECD significantly potentiated the sleeping time in mice induced by standard hypnotics viz. pentobarbitone sodium, diazepam, and meprobamate in a dose dependant manner. EECD showed significant analgesic properties as evidenced by the significant reduction in the number of writhes and stretches induced in mice by 1.2% acetic acid solution. It also potentiated analgesia induced by morphine and pethidine in mice. EECD inhibited the onset and the incidence of convulsion in a dose dependent manner against pentylenetetrazole (PTZ)-induced convulsion. The present study indicates that EECD has significant CNS depressant activities.

  6. CNS manifestation in progressive facial hemiatrophy (Romberg's disease). MRI findings and review of the literature

    International Nuclear Information System (INIS)

    Terstegge, K.; Henkes, H.; Kern, A.

    1993-01-01

    In this article the authors describe the clinical and MR imaging findings of the CNS in three female patients with PFH and present a comprehensive review of the literature. One of three PFH patients had partial epilepsy. MRI showed ventricular enlargement, white matter lesions, flattening of the cortical surface and meningeal adhesions homolateral to the facial hemiatrophy. Two other patients had completely normal intracranial findings. These findings confirm that cerebral hemiatrophy can occur in a subgroup of PFH patients. The MRI pattern, however, does not seem to be consistent with a simple atrophic or malnutrition process. The authors consider chronic localized meningoencephalitis with vascular involvement as a possible underlying mechanism for the occasional CNS involvement in PFH. (orig./MG) [de

  7. Nogo-A is a reliable oligodendroglial marker in adult human and mouse CNS and in demyelinated lesions

    DEFF Research Database (Denmark)

    Kuhlmann, Tanja; Remington, Leah; Maruschak, Brigitte

    2007-01-01

    to be strongly expressed in mature oligodendrocytes in vivo. In the present investigation we analyzed the expression patterns of Nogo-A in adult mouse and human CNS as well as in demyelinating animal models and multiple sclerosis lesions. Nogo-A expression was compared with that of other frequently used...... oligodendroglial markers such as CC1, CNP, and in situ hybridization for proteolipid protein mRNA. Nogo-A strongly and reliably labeled oligodendrocytes in the adult CNS as well as in demyelinating lesions and thus represents a valuable tool for the identification of oligodendrocytes in human and mouse CNS tissue...

  8. In vivo human apolipoprotein E isoform fractional turnover rates in the CNS.

    Directory of Open Access Journals (Sweden)

    Kristin R Wildsmith

    Full Text Available Apolipoprotein E (ApoE is the strongest genetic risk factor for Alzheimer's disease and has been implicated in the risk for other neurological disorders. The three common ApoE isoforms (ApoE2, E3, and E4 each differ by a single amino acid, with ApoE4 increasing and ApoE2 decreasing the risk of Alzheimer's disease (AD. Both the isoform and amount of ApoE in the brain modulate AD pathology by altering the extent of amyloid beta (Aβ peptide deposition. Therefore, quantifying ApoE isoform production and clearance rates may advance our understanding of the role of ApoE in health and disease. To measure the kinetics of ApoE in the central nervous system (CNS, we applied in vivo stable isotope labeling to quantify the fractional turnover rates of ApoE isoforms in 18 cognitively-normal adults and in ApoE3 and ApoE4 targeted-replacement mice. No isoform-specific differences in CNS ApoE3 and ApoE4 turnover rates were observed when measured in human CSF or mouse brain. However, CNS and peripheral ApoE isoform turnover rates differed substantially, which is consistent with previous reports and suggests that the pathways responsible for ApoE metabolism are different in the CNS and the periphery. We also demonstrate a slower turnover rate for CSF ApoE than that for amyloid beta, another molecule critically important in AD pathogenesis.

  9. Metastatic Ewing's sarcoma to the skull: CNS involvement excluded by MRI

    International Nuclear Information System (INIS)

    Taets ven Amerongen, A.H.M.; Kaiser, M.C.; Waal, F.C. de

    1987-01-01

    A case of metastatic Ewing's sarcoma to the skull is presented, demonstrating the superiority of magnetic resonance imaging over other imaging modalities to exclude CNS involvement. Precise delineation of different tumor components in extradural location contained in an intact dural rim together with compressed cortex showing no signs of tumorous involvement constituted an MRI appearance allowing us to exclude tumor outgrowth into the brain. (orig.)

  10. Rotorcraft Low Altitude CNS (Communications, Navigation and Surveillance) Benefit/Cost Analysis, Rotorcraft Operations Data

    Science.gov (United States)

    1989-09-01

    inventory of rotorcraft activity by mission and location. 17. Key Words 18. Distribution Statement Helicopter Helicopter Missions This document is available...helicopter is used to transport skiers /hikers to remote, normally inaccessible places. This mission is performed in rural or wilderness areas at altitudes...their applicability to the CNS benefit/cost analysis. Because of the uncertainty in the knowledge of the characteristics of both current and future

  11. Metastatic Ewing's sarcoma to the skull: CNS involvement excluded by MRI

    Energy Technology Data Exchange (ETDEWEB)

    Taets ven Amerongen, A.H.M.; Kaiser, M.C.; Waal, F.C. de

    1987-03-01

    A case of metastatic Ewing's sarcoma to the skull is presented, demonstrating the superiority of magnetic resonance imaging over other imaging modalities to exclude CNS involvement. Precise delineation of different tumor components in extradural location contained in an intact dural rim together with compressed cortex showing no signs of tumorous involvement constituted an MRI appearance allowing us to exclude tumor outgrowth into the brain.

  12. BOBATH THERAPY IN CORRECTION OF PSYCHOMOTOR DEVELOPMENT OF CHILDREN WITH ORGANIC INJURIES CNS

    OpenAIRE

    Bukhovets, B. O.; Romanchuk, A. P.

    2014-01-01

    The article represents therapy of Bobath such as one of the most effective author method which use in correction psychomotor development of children with disorders of musculoskeletal system. Bobath method is not new in the correction of movement disorders since last century and still supplementing and improving. In this work highlight topic of the effective use Bobath therapy in correction of psychomotor development in children age 3 – 6 years with organic involvement CNS. the experiment w...

  13. The glymphatic system in CNS health and disease: past, present and future

    OpenAIRE

    Plog, Benjamin A.; Nedergaard, Maiken

    2018-01-01

    The central nervous system (CNS) is unique in being the only organ system lacking lymphatic vessels to assist in the removal of interstitial metabolic waste products. Recent work has led to the discovery of the glymphatic system, a glial-dependent perivascular network that subserves a pseudo-lymphatic function in the brain. Within the glymphatic pathway, cerebrospinal fluid (CSF) enters brain via periarterial spaces, passes into the interstitium via perivascular astrocytic aquaporin-4, and th...

  14. Nanomaterials for delivery of nucleic acid to the central nervous system (CNS)

    DEFF Research Database (Denmark)

    Wang, Danyang; Wu, Lin-Ping

    2017-01-01

    -related disease, such as neurodegeneration and disorders, suitable, safe and effective drug delivery nanocarriers have to been developed to overcome the blood brain barrier (BBB), which is the most inflexible barrier in human body. Here, we highlight the structure and function of barriers in the central nervous...... system (CNS) and summary several types of nanomaterials which can be potentially used in the brain delivery nucleic acid....

  15. Prospective evaluation of delayed central nervous system (CNS) toxicity of hyperfractionated total body irradiation (TBI)

    International Nuclear Information System (INIS)

    Wenz, Frederik; Steinvorth, Sarah; Lohr, Frank; Fruehauf, Stefan; Wildermuth, Susanne; Kampen, Michael van; Wannenmacher, Michael

    2000-01-01

    Purpose: Prospective evaluation of chronic radiation effects on the healthy adult brain using neuropsychological testing of intelligence, attention, and memory. Methods and Materials: 58 patients (43 ± 10 yr) undergoing hyperfractionated total body irradiation (TBI) (TBI, 14.4 Gy, 12 x 1.2 Gy in 4 days) before bone marrow or peripheral blood stem cell transplantation were prospectively included. Twenty-one recurrence-free long-term survivors were re-examined 6-36 months (median 27 months) after completion of TBI. Neuropsychological testing included assessment of general intelligence, attention, and memory using normative, standardized psychometric tests. Mood status was controlled, as well. Test results are given as IQ scores (population mean 100) or percentiles for attention and memory (population mean 50). Results: The 21 patients showed normal baseline test results of IQ (101 ± 13) and attention (53 ± 28), with memory test scores below average (35 ± 21). Test results of IQ (98 ± 17), attention (58 ± 27), and memory (43 ± 28) showed no signs of clinically measurable radiation damage to higher CNS (central nervous system) functions during the follow-up. The mood status was improved. Conclusion: The investigation of CNS toxicity after hyperfractionated TBI showed no deterioration of test results in adult recurrence-free patients with tumor-free CNS. The median follow-up of 27 months will be extended.

  16. Decreased Cognitive/CNS Function in Young Adults at Risk for Hypertension: Effects of Sleep Deprivation

    Directory of Open Access Journals (Sweden)

    James A. McCubbin

    2012-01-01

    Full Text Available Hypertension has been linked to impaired cognitive/CNS function, and some of these changes may precede development of frank essential hypertension. The stress and fatigue of sleep deprivation may exacerbate these cognitive changes in young adults at risk. We hypothesize that individuals at risk for hypertension will show significant declines in cognitive function during a night of sleep deprivation. Fifty-one young adults were recruited for 28-hour total sleep deprivation studies. Hypertension risk was assessed by mildly elevated resting blood pressure and by family history of hypertension. A series of cognitive memory tasks was given at four test sessions across the sleep deprivation period. Although initially comparable in cognitive performance, persons at risk showed larger declines across the night for several indices of working memory, including code substitution, category, and order recall. These results suggest that cognitive/CNS changes may parallel or precede blood pressure dysregulation in the early stages of hypertension development. The role of CNS changes in the etiology of essential hypertension is discussed.

  17. Developmental hyperoxia alters CNS mechanisms underlying hypoxic ventilatory depression in neonatal rats.

    Science.gov (United States)

    Hill, Corey B; Grandgeorge, Samuel H; Bavis, Ryan W

    2013-12-01

    Newborn mammals exhibit a biphasic hypoxic ventilatory response (HVR), but the relative contributions of carotid body-initiated CNS mechanisms versus central hypoxia on ventilatory depression during the late phase of the HVR are not well understood. Neonatal rats (P4-5 or P13-15) were treated with a nonselective P2 purinergic receptor antagonist (pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, or PPADS; 125mgkg(-1), i.p.) to pharmacologically denervate the peripheral chemoreceptors. At P4-5, rats reared in normoxia showed a progressive decline in ventilation during a 10-min exposure to 12% O2 (21-28% decrease from baseline). No hypoxic ventilatory depression was observed in the older group of neonatal rats (i.e., P13-15), suggesting that the contribution of central hypoxia to hypoxic ventilatory depression diminishes with age. In contrast, rats reared in moderate hyperoxia (60% O2) from birth exhibited no hypoxic ventilatory depression at either age studied. Systemic PPADS had no effect on the ventilatory response to 7% CO2, suggesting that the drug did not cross the blood-brain barrier. These findings indicate that (1) CNS hypoxia depresses ventilation in young, neonatal rats independent of carotid body activation and (2) hyperoxia alters the development of CNS pathways that modulate the late phase of the hypoxic ventilatory response. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Kif13b Regulates PNS and CNS Myelination through the Dlg1 Scaffold.

    Directory of Open Access Journals (Sweden)

    Roberta Noseda

    2016-04-01

    Full Text Available Microtubule-based kinesin motors have many cellular functions, including the transport of a variety of cargos. However, unconventional roles have recently emerged, and kinesins have also been reported to act as scaffolding proteins and signaling molecules. In this work, we further extend the notion of unconventional functions for kinesin motor proteins, and we propose that Kif13b kinesin acts as a signaling molecule regulating peripheral nervous system (PNS and central nervous system (CNS myelination. In this process, positive and negative signals must be tightly coordinated in time and space to orchestrate myelin biogenesis. Here, we report that in Schwann cells Kif13b positively regulates myelination by promoting p38γ mitogen-activated protein kinase (MAPK-mediated phosphorylation and ubiquitination of Discs large 1 (Dlg1, a known brake on myelination, which downregulates the phosphatidylinositol 3-kinase (PI3K/v-AKT murine thymoma viral oncogene homolog (AKT pathway. Interestingly, Kif13b also negatively regulates Dlg1 stability in oligodendrocytes, in which Dlg1, in contrast to Schwann cells, enhances AKT activation and promotes myelination. Thus, our data indicate that Kif13b is a negative regulator of CNS myelination. In summary, we propose a novel function for the Kif13b kinesin in glial cells as a key component of the PI3K/AKT signaling pathway, which controls myelination in both PNS and CNS.

  19. Optimization of dipeptidic inhibitors of cathepsin L for improved Toxoplasma gondii selectivity and CNS permeability.

    Science.gov (United States)

    Zwicker, Jeffery D; Diaz, Nicolas A; Guerra, Alfredo J; Kirchhoff, Paul D; Wen, Bo; Sun, Duxin; Carruthers, Vern B; Larsen, Scott D

    2018-06-01

    The neurotropic protozoan Toxoplasma gondii is the second leading cause of death due to foodborne illness in the US, and has been designated as one of five neglected parasitic infections by the Center for Disease Control and Prevention. Currently, no treatment options exist for the chronic dormant-phase Toxoplasma infection in the central nervous system (CNS). T. gondii cathepsin L (TgCPL) has recently been implicated as a novel viable target for the treatment of chronic toxoplasmosis. In this study, we report the first body of SAR work aimed at developing potent inhibitors of TgCPL with selectivity vs the human cathepsin L. Starting from a known inhibitor of human cathepsin L, and guided by structure-based design, we were able to modulate the selectivity for Toxoplasma vs human CPL by nearly 50-fold while modifying physiochemical properties to be more favorable for metabolic stability and CNS penetrance. The overall potency of our inhibitors towards TgCPL was improved from 2 μM to as low as 110 nM and we successfully demonstrated that an optimized analog 18b is capable of crossing the BBB (0.5 brain/plasma). This work is an important first step toward development of a CNS-penetrant probe to validate TgCPL as a feasible target for the treatment of chronic toxoplasmosis. Copyright © 2018 Elsevier Ltd. All rights reserved.

  20. Regulation of Adult CNS Axonal Regeneration by the Post-transcriptional Regulator Cpeb1

    Directory of Open Access Journals (Sweden)

    Wilson Pak-Kin Lou

    2018-01-01

    Full Text Available Adult mammalian central nervous system (CNS neurons are unable to regenerate following axonal injury, leading to permanent functional impairments. Yet, the reasons underlying this regeneration failure are not fully understood. Here, we studied the transcriptome and translatome shortly after spinal cord injury. Profiling of the total and ribosome-bound RNA in injured and naïve spinal cords identified a substantial post-transcriptional regulation of gene expression. In particular, transcripts associated with nervous system development were down-regulated in the total RNA fraction while remaining stably loaded onto ribosomes. Interestingly, motif association analysis of post-transcriptionally regulated transcripts identified the cytoplasmic polyadenylation element (CPE as enriched in a subset of these transcripts that was more resistant to injury-induced reduction at the transcriptome level. Modulation of these transcripts by overexpression of the CPE binding protein, Cpeb1, in mouse and Drosophila CNS neurons promoted axonal regeneration following injury. Our study uncovered a global evolutionarily conserved post-transcriptional mechanism enhancing regeneration of injured CNS axons.