A Budd-Chiari Syndrome Due to C Protein Deficiency: A Case Report at YaoundéGeneral Hospital (Cameroon)

Primary Budd-Chiari syndrome (BCS) is a spontaneously fatal disease characterized by an obstruction of the hepatic venous outflow tract due to thrombosis or a primary disease of the venous wall. The primary form of BCS is extremely rare. This is a disease mainly affecting young adults of both sexes. Clinical manifestations are variable;they can be asymptomatic, acute, or subacute but mostly chronic. Several causes have been identified, such as myeloproliferative syndrome, antiphospholipid syndrome, paroxysmal nocturnal hemoglobinuria, and inherited thrombotic disorders. Data on primary BCS in Sub-Saharan Africa is rare as most publications available are case reports. In these reports, the causes are unknown with poor prognosis in most cases often leading to patient death. We herein present a case report of a male patient diagnosed with a primary BCS at Yaoundé General Hospital (Cameroon) caused by a Protein C deficiency who presented with ascites decompensating liver cirrhosis. Treatment was based on anticoagulants, diuretics and laxatives administration. Two years after the diagnosis, the patient is alive with clinical and paraclinical improvement.

Protein C deficiency with venous and arterial thromboembolic events

Protein C(PC)is a key component of the vitamin K-dependent coagulation pathway.It exerts anticoagulant effects by inactivating factors V and VIII.Acquired or inherited PC deficiency results in a prothrombotic state,with presentations varying from asymptomatic to venous thromboembolism.However,there has been an increasing number of reports linking PC deficiency to arterial thromboembolic events,such as myocardial infarction and ischemic stroke.This editorial focuses on the association between PC deficiency and thromboembolism,which may provide some insights for treatment strategy and scientific research.

Systemic lupus erythematosus combined with primary hyperfibrinolysis and protein C and protein S deficiency:A case report

BACKGROUND Systemic lupus erythematosus(SLE)is an autoimmune disease characterized by systemic involvement and multiple autoantibodies in the serum.Patients with protein C(PC)and protein S(PS)deficiency are prone to thrombosis.In contrast,patients with primary hyperfibrino-lysis tend to bleed.CASE SUMMARY A 52-year-old female patient with bilateral pleural effusion was diagnosed with"tuberculous pleurisy"and treated with anti-tuberculosis drugs and prednisone.The coagulation-related laboratory results showed decreased fibrinogen,PC activity,PS activity,and antithrombinШactivity.The immune-related laboratory results showed positive antinuclear antibody,anti-Smith antibody,anticardiolipin antibody(ACL),anti-β2-glycoprotein I antibody(aβ2GPI)and direct Coomb’s test and decreased complement 3 and complement 4.Thoracoscopy was performed and bloody pleural fluid was drained.Pathology of the pleural biopsy showed lymphocytes,plasma cells,and a few eosinophils in adipose and fibrous connective tissue.Results of whole exome sequencing of blood showed no genetic mutations suggesting the presence of hereditary hematological diseases.The patient was finally diagnosed with SLE and primary hyperfibrinolysis,and was treated with prednisolone,hydroxychloroquine,and compound cyclophosphamide.CONCLUSION PC and PS deficiency in SLE might be related to ACL and aβ2GPI.SLE and primary hyperfibrinolysis can coexist in one patient,with both a risk of thrombosis and a risk of bleeding.

STRUCTURAL REQUIREMENT FOR CLUSTERS TO BE RECONSTITUTED WITH THE FeMoCo DEFICIENT MOLYBDENUM IRON PROTEIN

By incubating the reduced MoFe protein from Azotobacter vinelandii with O phenanthroline under air and chromatographying the incubated solution on Sephadex G 25 column, inactive MoFe protein could be obtained. Its acetylene reduction activity was remarkably recovered not only by incubation with the reconstituent solution composed of KMnO 4,ferric homocitrate, Na 2S and dithiothreitol,Azotobacter vinelandii with O phenanthroline under air and chromatographying the incubated solution on Sephadex G 25 column, inactive MoFe protein could be obtained. Its acetylene reduction activity was remarkably recovered not only by incubation with the reconstituent solution composed of KMnO 4,ferric homocitrate, Na 2S and dithiothreitol, with O phenanthroline under air and chromatographying the incubated solution on Sephadex G 25 column, inactive MoFe protein could be obtained. Its acetylene reduction activity was remarkably recovered not only by incubation with the reconstituent solution composed of KMnO 4,ferric homocitrate, Na 2S and dithiothreitol, but also with a mixture of 4Fe∶4S clusters and another cluster which had two structure units of 1Mo∶3Fe∶4S bridged by three -OCH 3- at the Mo atoms. Neither the reconstituent solution nor the mixture could reactivate apo MoFe proteins from the mutants deleting nifE and nifH genes and from the mutant UW 45 , which could be reactivated by the FeMoco extracted from the MoFe protein. The results indicated that the FeMoco deficient MoFe proteins from these mutants seemed to be reconstituted only by the clusters which were probably structures only similar to FeMoco. The partially metallocluster deficient MoFe protein could be reconstituted by the clusters with a certain kind of structure and composition; and was changed into different nitrogenase proteins with the ability to fix nitrogen.

Potential protein–phenotype correlation in three lipopolysaccharideresponsive beige-like anchor protein-deficient patients

BACKGROUND Patients with lipopolysaccharide(LPS)-responsive beige-like anchor protein(LRBA)deficiency have a variety of clinical symptoms,but there is no apparent genotype–phenotype correlation,and patients carrying the same mutations may have different phenotypes.Therefore,it is not easy for doctors to make a decision regarding hematopoietic stem cell transplantation(HSCT)for LRBA-deficient patients.We hypothesized that there may be a protein–phenotype correlation to indicate HSCT for LRBA-deficient patients.AIM To report on three Chinese LRBA-deficient patients and determine the correlation between residual protein expression and disease phenotypes.METHODS Clinical data of three Chinese LRBA-deficient patients were collected,and protein levels were detected by Western blot analysis.In addition,LRBA mutation information of another 83 previously reported patients was summarized.RESULTS All the major clinical findings indicated enteropathy,but patients 1 and 3 presented with more severe symptoms than patient 2.Endoscopy and histology indicated nonspecific colitis for patients 1 and 3 but Crohn's disease-like colitis for patient 2.Compound heterozygous mutations in LRBA were found in patient 1,and homozygous mutations in LRBA were found in patient 2 and patient 3.Only patient 2 responded well to traditional immunosuppressive treatment.Residual expression of the LRBA protein in patients 1 and 3 was very low,but in patient 2,a more than 0.5-fold in expression of the LRBA protein was found compared to that in the control.After HSCT,patient 1 had increased LRBA protein expression.We summarized the genetic information of 86 patients,and the mutations in patients 1 and 3 were novel mutations.CONCLUSION We described three Chinese LRBA-deficient patients,two of whom carried novel mutations.These patients had no genotype-phenotype correlations,but their residual LRBA protein expression might be associated with disease outcome and could be an indicator for HSCT.

EFFECTS OF ANTICOAGULATION PROTEIN DEFECT IN MATERNAL PLASMA ON SPONTANEOUS ABORTION

Objective To investigate the mechanism of anticoagulation protein defect in the pathogenesis of unexplained recurrent miscarriage. Methods Fifty-seven patients with a history of unexplained abortion were enrolled as the investigation group for tests of protein C, protein S, antithrombinⅢ(AT-Ⅲ), as well as activated protein C resistance (APC-R). The control group con-sisted of fifty healthy women with a history of normal pregnancy and delivery. Blood samples were obtained for measuring serum activity of protein C, protein S, AT-Ⅲ, and APC-R. Patients with positive APC-R were tested for factorⅤ(FⅤ) Lei-den gene mutation by PCR-RFLP method. Results Of the 57 patients, 12 (21.1%), 1 (1.8%), and 5 (8.8%) cases were found with protein S, protein C, and AT-Ⅲdeficiency respectively, and 13 (22.8%) cases with positive results of APC-R. Of the control group, no protein C or AT-Ⅲdeficiency was ever found, whereas 2 (4.0%) volunteers were presented with protein S deficiency and 3 (6.0%) with positive results of APC-R. No FⅤLeiden gene mutation was identified in all the patients with positive APC-R results. Late spontan-eous abortion cases had higher incidence of anticoagulation protein defect than the early cases. Conclusion Anticoagulation protein defect may play a role in the pathogenesis of fetal loss, especially for those occurr-ing in late stage of pregnancy.

Acute myocardial infarction after initially diagnosed with unprovoked venous thromboembolism: A case report

BACKGROUND Protein C deficiency is typically associated with venous thromboembolism;however,arterial thrombosis has been reported in several cases.We report the case of a patient with pulmonary thromboembolism and deep vein thrombosis following acute myocardial infarction with high thrombus burden.CASE SUMMARY A 40-year-old man was diagnosed with pulmonary thromboembolism and deep vein thrombosis without any provoking factors.The patient was treated with anticoagulants for six months,which were then discontinued.Three months after the discontinuation of anticoagulant therapy,the patient was hospitalized with chest pain and diagnosed with acute myocardial infarction with high thrombus burden.Additional tests revealed protein C deficiency associated with thrombophilia.The patient was treated with anticoagulants combined with dual antiplatelet agents for 1 year after percutaneous coronary intervention,and no recurrent events were reported during a follow-up period of 5 years.CONCLUSION Recurrent thromboembolic events including acute myocardial infarction with thrombus should be considered an alarming sign of thrombophilia.

Livedoid Vasculopathy Secondary to Protein C Deficiency:A Case Successfully Treated With Rivaroxaban

Introduction:Livedoid vasculopathy is a chronic noninflammatory skin disease secondary to hypercoagulable states.No therapeutic guideline has yet been established for livedoid vasculopathy.We herein report a case of livedoid vasculopathy secondary to protein C deficiency that was successfully treated with rivaroxaban.Case presentation:A 31-year-old Thai woman who had been diagnosed with livedoid vasculopathy 10 years previously presented with a 2-month history of worsening leg ulcers and failure to respond to aspirin,colchicine,and pentoxifylline.Further investigations confirmed protein C deficiency.Rivaroxaban was initiated,and clinical improvement was achieved in 8 weeks.Discussion:When livedoid vasculopathy is confirmed by skin biopsy,additional investigations for hypercoagulable states should be performed to exclude secondary causes.Identification of the causes of livedoid vasculopathy can direct physicians to therapeutic options based on previously reported cases of successful treatment.Our patient,whose livedoid vasculopathy was caused by protein C deficiency,responded well to rivaroxaban.Conclusion:Protein C deficiency results in a hypercoagulable state,and affected patients can present with livedoid vasculopathy.The anticoagulant rivaroxaban has been beneficial in the treatment of livedoid vasculopathy.

Elevated Carbon Dioxide Level Suppresses Nutritional Quality of Lettuce and Spinach

Rising global CO2 levels are a major factor that impacts not only the environment but also many plant functions including growth, productivity and nutritional quality. The study examined the impact of elevated [CO2] on nutritional quality and growth characteristics of lettuce (Lactuca sativa) and spinach (Spinacia oleracea). Elevated [CO2] decreased the concentration of many important nutrients including nitrogen (protein), potassium and phosphorus in the edible parts of both lettuce and spinach. The nitrogen concentration in lettuce shoots was reduced by more than 30% at elevated [CO2] compared to the plants grown at ambient level of CO2. Similarly the concentration of a number of micronutrients including sulfur, zinc, copper and magnesium, was depressed in lettuce shoots. Although the total phenolic content and antioxidant capacity were higher in lettuce at elevated CO2, they were not affected in spinach. The photosynthetic activity was variable among the plant species while there was no increase in the carbon accumulation in these plants at elevated [CO2]. However, there was significant reduction in the leaf stomatal conductance in both lettuce and spinach in response to higher [CO2], which is likely affect both water loss from the leaves and their photosynthetic activity. The results indicate a broad adverse impact of rising [CO2] on the nutritional quality of commonly consumed leafy vegetables namely, lettuce and spinach.

Combined liver-kidney transplantation for rare diseases

Combined liver and kidney transplantation(CLKT)is indicated in patients with failure of both organs,or for the treatment of end-stage chronic kidney disease(ESKD)caused by a genetic defect in the liver.The aim of the present review is to provide the most up-to-date overview of the rare conditions as indications for CLKT.They are major indications for CLKT in children.However,in some of them(e.g.,atypical hemolytic uremic syndrome or primary hyperoxaluria),CLKT may be required in adults as well.Primary hyperoxaluria is divided into three types,of which type 1 and 2 lead to ESKD.CLKT has been proven effective in renal function replacement,at the same time preventing recurrence of the disease.Nephronophthisis is associated with liver fibrosis in 5%of cases and these patients are candidates for CLKT.In alpha 1-antitrypsin deficiency,hereditary C3 deficiency,lecithin cholesterol acyltransferase deficiency and glycogen storage diseases,glomerular or tubulointerstitial disease can lead to chronic kidney disease.Liver transplantation as a part of CLKT corrects underlying genetic and consequent metabolic abnormality.In atypical hemolytic uremic syndrome caused by mutations in the genes for factor H,successful CLKT has been reported in a small number of patients.However,for this indication,CLKT has been largely replaced by eculizumab,an anti-C5 antibody.CLKT has been well established to provide immune protection of the transplanted kidney against donor-specific antibodies against class I HLA,facilitating transplantation in a highly sensitized recipient.

AB021.Discovery of a new role for the WNK1 kinase in corneal wound healing

Background:Damage to the corneal epithelium triggers important changes in the composition of the extracellular matrix(ECM)to which the basal human corneal epithelial cells(hCECs)attach.These changes are perceived by integrins,a family of trans-membrane receptors that activate different intracellular signalling pathways,ultimately leading to re-epithelialization of the injured epithelium.Our goal is to study the impact of the pharmacological inhibition/activation of specific signal transduction mediators on corneal wound healing using both monolayers of hCECs and tissue-engineered human corneas(hTECs)as in vitro models.Methods:hTECs were produced by the self-assembly approach and wounded with a 8-mm biopsy punch.Total RNA and proteins were isolated from the wounded and unwounded hTECs to conduct gene profiling analyses and protein kinase arrays.The wounded tissues were then incubated either with the lysine deficient protein kinase 1(WNK1)inhibitor WNK463,the WNK1 indirect agonist AM1241,or with the vehicle alone(DMSO;negative control)and wound healing was monitored for 6 days.The impact of WNK1 inhibition/activation on hCECs monolayers was determined using scratch wound assays.Results:Gene profiling analyses and protein kinases arrays revealed that expression and activity of several mediators from the integrin-dependent signalling pathways were altered in response to the ECM changes taking place during corneal wound healing.Phosphorylation of the WNK1 kinase turned out to be the most striking activation event occurring during wound healing.Since the pharmacological inhibition of WNK1 by WNK463 significantly reduced the rate of corneal wound closure in our hTECs and hCECs monolayers compared to their respective negative controls,we believe that the pharmacological activation of WNK1 could turn out to be an interesting avenue to accelerate corneal wound closure.Conclusions:These results will contribute to a better understanding of the cellular and molecular mechanisms involved in corneal wound healing.Furthermore,they identified a new function for the WNK1 kinase in corneal wound healing and might lead to the identification of a new therapeutic target in the field of corneal wounds.

Sustainable food industrial waste management through single cell protein production and characterization of protein enriched bread

Production of single cell protein(SCP)from food waste is one of the promising approaches for excellent waste management.In the present study,SCP was produced through submerged fermentation using selected food wastes(banana peel,citrus peel,carrot pomace and potato peel).During process optimization,combinations of various temperature and nitrogen sources were studied for optimum SCP yield(g/100g).The results indicated that maximum SCP yield was obtained at 30℃ for 7 days on potato peels,whereas citrus and banana peels exhibited the lowest SCP yield at the same process conditions.The SCP compositional analysis indicated that the amount of non-essential amino acids was significantly higher than wheat flour.Furthermore,SCP enriched bread was prepared by adding SCP at different concentrations(0,4,8,and 12%).The organoleptic properties indicated that SCP addition up to 4%was acceptable to prepare protein enriched bread.Thus,SCP may be effectively used for food waste management and food security.