scholarly journals Baseline HDAC6 and TFF3 proteins overexpression as prognostic markers of lupus nephritis relapse

2020 ◽  
Vol 9 (2) ◽  
pp. e14-e14
Author(s):  
Eman Hassan Abdelbary ◽  
Noha Farouk Ahmed ◽  
Adel Abdelmohsen Ghorab
Keyword(s):  
Lupus Nephritis ◽  
Serum Creatinine ◽  
Lupus Erythematosus ◽  
Kidney Diseases ◽  
Activity Index ◽  
Kidney Injury ◽  
Class Iii ◽  
Clinicopathologic Characteristics ◽  
Chronicity Index

Introduction: Lupus nephritis (LN) is a substantial manifestation of systemic lupus erythematosus (SLE). HDAC6 is overexpressed in various kidney diseases, and its inhibition slows kidney injury progression. Urinary TFF3 increases in chronic kidney diseases (CKDs) and may be associated with patient’s outcome. Objectives: This study aimed to examine the relationship between renal HDAC6 and TFF3 proteins expression and with clinicopathologic characteristics and outcome of LN. Patients and Methods: HDAC6 and TFF3 proteins’ expression was immunohistochemically detected in 56 cases of LN. They were correlated to patients’ age, gender, urinary 24 hours protein and serum creatinine levels at baseline and during follow up. Additionally, they were correlated to LN classes, activity index (AI) and chronicity index (CI) and relapse free survival (RFS). Results: HDAC6 overexpression was significantly associated with serum creatinine and 24 hours proteinuria levels at baseline (P = 0.041 and P =0.026 respectively) and during follow up (P < 0.001). It was associated with AI and CI of class III and IV LN (P = 0.047 and 0.003 respectively). TFF3 overexpression was associated with higher serum creatinine and more proteinuria at baseline (P = 0.015 and 0.001 respectively) and during follow up (P < 0.001). It was significantly associated with higher CI (P = 0.001). Both markers were associated with shorter RFS (P < 0.001). Conclusion: HDAC6 and TFF3 proteins are associated with clinicopathologic features of renal damage in LN. They are reliable predictors of patients’ RFS, which makes them good candidates for risk stratification of patients and targeted therapy.

scholarly journals Change of Renal Gallium Uptake Correlated with Change of Inflammation Activity in Renal Pathology in Lupus Nephritis Patients

2021 ◽  
Vol 10 (20) ◽  
pp. 4654
Author(s):  
Tsu-Yi Hsieh ◽  
Yi-Ching Lin ◽  
Wei-Ting Hung ◽  
Yi-Ming Chen ◽  
Mei-Chin Wen ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Left Kidney ◽  
Renal Pathology ◽  
Class Iii ◽  
Stage Renal Disease ◽  
End Stage ◽  
Active Inflammation ◽  
Histological Results

Background: Lupus nephritis (LN) often lead to end-stage renal disease in systemic lupus erythematosus patients. This study aimed to investigate the clinical application of renal gallium-67 scans for determining renal histological parameters in LN patients. Methods: Between 2006 and 2018, 237 biopsy-proven and 35 repeat biopsies LN patients who underwent renal gallium scans before or after biopsy were included for analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. A delayed 48-h gallium scan was performed and interpreted by semiquantitative methods using left kidney/spine (K/S) ratio. The renal histological results were compared with gallium uptake. Results: Out of 237 participants, 180 (76%) had proliferative LN. Baseline gallium left K/S ratio was significantly higher in class IV LN as compared to class III (median (interquartile range, IQR): 1.16 (1.0–1.3), 0.95 (0.9–1.1), respectively, p < 0.001). Furthermore, changes in gallium uptake between two biopsies were positively correlated with changes activity index (r = 0.357, p = 0.035), endocapillary hypercellularity (r = 0.385, p = 0.032), and neutrophils infiltration (r = 0.390, p = 0.030) in renal pathology. Conclusions: Renal gallium uptake is associated with active inflammation in LN. Changes in renal gallium uptake positively correlated with changes in activity index in renal pathology.

scholarly journals P0442RELATED FACTORS IN THE DEVELOPMENT OF LUPUS NEPHRITIS IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Andres Ribas ◽  
Isabel Galcerán ◽  
Sara Outón ◽  
Tarek Salman ◽  
Clara Barrios ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Lupus Anticoagulant ◽  
Protective Factor ◽  
Analytical Data ◽  
Class Iii ◽  
Systemic Lupus ◽  
Complement Factors ◽  
Patients At Risk

Abstract Background and Aims Lupus Nephritis (LN) is a severe complication of Systemic Lupus Erytemathosus (SLE). This is the main reason why identifying predisposing factors to differentiate patients at risk of developing LN is so important. Method Retrospective study of patients with SLE diagnosed between years 2008-2018 in our center. Demographic, clinical and analytical data have been collected. Results We included 171 patients, 48 (28%) with diagnose of LN. Age at diagnose of SLE was 39,51 ± 15,40 years, being more frequent in women 151 (87,5%). Time of follow-up since SLE diagnose until development of LN was of 3 ± 5, 3 years. Respectful to the LN classification we found: 4 (8%) class I LN, 6 (12.5%) class II LN, 15 (31.2%) class III LN, 19 (39.5%) class IV LN and 4 (8%) class V LN. At diagnose of SLE, the following variables, where related to developing LN: CH50 [HR: 1,039; CI (95%): 1,004-1,064; p=0,024], C3 [HR: 1,029; CI (95%): 1,016-1,042; p&lt;0,001, titer of Anti- DNACrithidia [HR: 4,364; CI(95%): 1,26-15,064; p=0,02], AntiSM [HR: 4,634, CI (95%) 1,76-12,17, p=0,002], ACA IgG [HR: 7,5; CI (95%): 2,3 -24,449; p=0,001] and Lupus anticoagulant [HR: 4,97; CI (95%): 1,591-15,533; p=0,006]. Treatment with hidroxicloroquine is a protective factor against developing LN [HR: 0,17; CI (95%): 0,063-0,511; p=0.001]. At diagnose of LN, complement factors and titer of anti-DNA crithidia show a positive correlation when compared to the initial determinations: C3 [r= 0,605 (p&lt;0,001]); C1q [r= 0,861 (p=0,006)]; CH50 [r= 0,981 (p&lt;0,001), anti- DNACrithidia [r= 0,529 (p&lt;0,001)], anti-Sm [r=0.8, )p=0.001)]. Conclusion Consumption of complement factors, high titers of anti-DNAcrithidia, Anti-SM, ACA IgG and Lupus anticoagulant are related to a future LN development at SLE diagnose. Moreover, we see an increase of their titer once we diagnose LN. Otherwise, treatment with hidroxicloroquine seems to be a protective factor.

Therapeutic potential of allogeneic mesenchymal stromal cells transplantation for lupus nephritis

Lupus ◽  
2018 ◽  
Vol 27 (13) ◽  
pp. 2161-2165 ◽  
Author(s):  
J Barbado ◽  
S Tabera ◽  
A Sánchez ◽  
J García-Sancho
Keyword(s):  
Lupus Nephritis ◽  
Mesenchymal Stromal Cells ◽  
Lupus Erythematosus ◽  
Stromal Cells ◽  
Therapeutic Potential ◽  
Activity Index ◽  
Disease Activity Index ◽  
Controlled Clinical Trial ◽  
Allogeneic Mscs

Animal and human studies have suggested the potential of mesenchymal stromal cells (MSCs) to treat systemic lupus erythematosus (SLE). Here, we present the results of compassionate MSC treatments for three SLE patients to provide the proof of concept for a randomized and controlled clinical trial. Three patients of different ethnicities who suffer from chronic SLE, and who presented with class IV active proliferative nephritis confirmed by biopsy, were treated with allogeneic MSCs from healthy donors. Ninety million cells were infused intravenously into each patient during high and very high activity disease flare-ups and follow-up was continued for 9 months. Multi-organic affectation was quantified by the SLE disease activity index (SLEDAI), and indicators of lupus nephritis activity, such as proteinuria, as well as lymphocyte and monocyte antigens and anti-HLA antibodies were measured at 1, 3, 6, and 9 months after treatment. Proteinuria levels improved dramatically during the 1st month after treatment and the ameliorations were sustained throughout the follow-up period. SLEDAI scores revealed early, durable, and substantial remissions that were complete for two patients and partial for the third patient and that permitted medication doses to be reduced 50–90%. These favourable outcomes support completion of the randomized and controlled MSC trial for SLE.

Interleukin-34 as a marker for subclinical proliferative lupus nephritis

Lupus ◽  
2020 ◽  
Vol 29 (6) ◽  
pp. 607-616
Author(s):  
Asmaa SM Abdel-Rehim ◽  
Nesrine A Mohamed ◽  
Marwa M Shakweer
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Renal Involvement ◽  
Clinical Manifestations ◽  
Surrogate Marker ◽  
Disease Activity Index ◽  
Class Iii ◽  
Group I ◽  
Dsdna Antibodies

Background Lupus nephritis (LN) is an ominous manifestation of systemic lupus erythematosus (SLE). Clinical renal affection is present in about 70% of lupus patients, and more patients have histological evidence of renal involvement without clinical manifestations. This study aimed to investigate the potential role of serum interleukin-34 (IL-34) as an early marker for the detection of silent LN. Methods Thirty-three lupus patients with silent LN (group I), 37 patients with clinical LN (group II) and 20 controls were included. The SLE Disease Activity Index (SLEDAI), IL-34, anti-dsDNA antibodies and renal biopsy were assessed in all patients. Results Serum IL-34 levels were significantly higher in all lupus patients compared to healthy controls ( p < 0.001) and showed a significant positive correlation with SLEDAI score. SLE patients with positive anti-dsDNA antibodies had more active disease according to SLEDAI and higher levels of IL-34 than those with negative anti-dsDNA antibodies. In both studied groups, serum IL-34 levels were significantly higher in patients with proliferative LN (class III and class IV) than those with non-proliferative lupus (class II and class V) and controls. Yet, in both groups, IL-34 was not useful in differentiating active from chronic renal affection. Conclusion In lupus patients with insignificant proteinuria, serum levels of IL-34 distinguished the different histological classes of subclinical LN. Serum IL-34 may be used as a surrogate marker for early renal affection in silent LN, especially the proliferative type.

scholarly journals The ISN/RPS 2016 classification predicts renal prognosis in patients with first-onset class III/IV lupus nephritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asaka Hachiya ◽  
Munetoshi Karasawa ◽  
Takahiro Imaizumi ◽  
Noritoshi Kato ◽  
Takayuki Katsuno ◽  
...  
Keyword(s):  
Complete Remission ◽  
Lupus Nephritis ◽  
Clinical Outcomes ◽  
Lupus Erythematosus ◽  
Cox Regression ◽  
Interstitial Fibrosis ◽  
Activity Index ◽  
Class Iii ◽  
Cox Regression Analysis ◽  
First Onset

AbstractLupus nephritis (LN) is a life-threatening complication of systemic lupus erythematosus. The 2003 pathological classification of LN was revised in 2016; it quantitatively evaluates the interstitium in addition to the glomeruli. We performed a retrospective multi-centre cohort study and investigated the utility of the 2016 classification—including the activity index (AI), chronicity index (CI), and each pathological component to predict complete remission or renal function decline, defined as 1.5-fold increase in serum creatinine levels—and compare with that of the 2003 classification. Ninety-one consecutive adult patients with first-onset class III/IV LN who were newly prescribed any immunosuppressants were enrolled and followed up for a median of 51 months from January 2004. Cox regression analysis demonstrated the subclasses based on the 2003 classification, which mainly evaluate glomerular lesions, were not associated with clinical outcomes. After adjustments for estimated glomerular filtration rate and urinary protein levels, higher CI and higher interstitial fibrosis and lower hyaline deposit scores were associated with renal functional decline. Similarly, higher CI and interstitial inflammation scores were associated with failure to achieve complete remission. Therefore, the 2016 classification can predict the clinical outcomes more precisely than the 2003 classification.

scholarly journals Changing patterns in clinical–histological presentation and renal outcome over the last five decades in a cohort of 499 patients with lupus nephritis

2018 ◽  
Vol 77 (9) ◽  
pp. 1318-1325 ◽  
Author(s):  
Gabriella Moroni ◽  
Paolo Gilles Vercelloni ◽  
Silvana Quaglini ◽  
Mariele Gatto ◽  
Davide Gianfreda ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Activity Index ◽  
Progressive Increase ◽  
Renal Outcome ◽  
Rank Test ◽  
Renal Survival ◽  
Chronicity Index

ObjectivesTo evaluate changes in demographic, clinical and histological presentation, and prognosis of lupus nephritis (LN) over time.Patients and methodsWe studied a multicentre cohort of 499 patients diagnosed with LN from 1970 to 2016. The 46-year follow-up was subdivided into three periods (P): P1 1970–1985, P2 1986–2001 and P3 2002–2016, and patients accordingly grouped based on the year of LN diagnosis. Predictors of patient and renal survival were investigated by univariate and multivariate proportional hazards Cox regression analyses. Survival curves were compared using the log-rank test.ResultsA progressive increase in patient age at the time of LN diagnosis (p<0.0001) and a longer time between systemic lupus erythematosus onset and LN occurrence (p<0.0001) was observed from 1970 to 2016. During the same period, the frequency of renal insufficiency at the time of LN presentation progressively decreased (p<0.0001) and that of isolated urinary abnormalities increased (p<0.0001). No changes in histological class and activity index were observed, while chronicity index significantly decreased from 1970 to 2016 (p=0.023). Survival without end-stage renal disease (ESRD) was 87% in P1, 94% in P2% and 99% in P3 at 10 years, 80% in P1 and 90% in P2 at 20 years (p=0.0019). At multivariate analysis, male gender, arterial hypertension, absence of maintenance immunosuppressive therapy, increased serum creatinine, and high activity and chronicity index were independent predictors of ESRD.ConclusionsClinical presentation of LN has become less severe in the last years, leading to a better long-term renal survival.

scholarly journals Association of Intrarenal B-Cell Infiltrates with Clinical Outcome in Lupus Nephritis: A Study of 192 Cases

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Yan Shen ◽  
Chuan-Yin Sun ◽  
Feng-Xia Wu ◽  
Yi Chen ◽  
Min Dai ◽  
...  
Keyword(s):  
B Cells ◽  
Lupus Nephritis ◽  
B Cell ◽  
Lupus Erythematosus ◽  
Kidney Diseases ◽  
Activity Index ◽  
Disease Activity Index ◽  
Immunological Responses ◽  
Renal Biopsies ◽  
Stage Renal Disease

Background. Lupus nephritis (LN) remains a major cause of morbidity and end-stage renal disease. Dysfunction of B lymphocytes is thought to be important in the pathogenesis of SLE/LN. Intrarenal B cells have been found in several forms of inflammatory kidney diseases although their role in LN renal is not well defined.Methods. Intrarenal B cells were analyzed in 192 renal biopsies from patients diagnosed with lupus nephritis. Immunohistochemical staining of serial sections was performed for each LN patient using CD20, CD3, and CD21 antibodies.Results. Intrarenal B cells were more likely to be associated with class IV LN and were mainly distributed in the renal interstitium, with very few in the glomerulus. The systemic lupus erythematosus disease activity index (SLEDAI), blood urea nitrogen, and serum creatinine levels were all significantly greater in the LN-B cell groups (allP<0.05). LN renal activity and chronicity indices correlated with B-cells infiltrates (allP<0.0001). Renal biopsies were classified into four distinct categories according to the organizational grade of inflammatory cell infiltrates. Germinal center- (GC-) like structures were not identified in any LN biopsies.Conclusion. It is hypothesized that intrarenal B cells enhance immunological responses and exaggerate the local immune response to persisting autoimmune damage in the tubulointerstitium.

Efficacy and safety of bortezomib in refractory lupus nephritis: a single-center experience

Lupus ◽  
2019 ◽  
Vol 29 (2) ◽  
pp. 118-125 ◽  
Author(s):  
A Segarra ◽  
K V Arredondo ◽  
J Jaramillo ◽  
E Jatem ◽  
M T Salcedo ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Lupus Nephritis ◽  
Partial Response ◽  
Opportunistic Infections ◽  
Activity Index ◽  
Kidney Injury ◽  
Close Monitoring ◽  
Efficacy And Safety ◽  
Bortezomib Treatment

Background and Objectives Resistant lupus nephritis (LN) has been associated with the persistence of long-lived plasma cells. Preliminary studies identified bortezomib as a potential treatment option for patients with refractory LN. The aim of this study was to analyze the efficacy and safety of bortezomib in the treatment of severe refractory LN. Methods This retrospective study included 12 female patients diagnosed for the first time with class IV or IV/V LN with acute or rapidly progressive kidney injury ( n = 11) and/or severe nephrotic syndrome ( n = 1) who showed resistance to induction therapy with cyclophosphamide, steroids, mycophenolate, and rituximab, and were treated with either intravenous or subcutaneous bortezomib plus intravenous dexamethasone. Results All patients with acute or rapidly progressive kidney injury showed a significant reduction in both biochemical and immunological activity after a mean of 6 (minimum 5, maximum 7) weekly cycles of bortezomib regimen, with a significant increase in C3 levels and a significant decrease of anti-ds DNA antibody titers, Systemic Lupus Erythematosus Disease Activity Index score, serum creatinine, and proteinuria. One patient (8.3%) achieved a complete response, and 10 patients (83.4%) achieved a partial response. During follow-up, all these patients maintained partial responses under treatment with mycophenolate and low-dose glucocorticoids. The patient with refractory nephrotic syndrome showed a partial response but relapsed 11 months after the end of bortezomib treatment and was resistant to treatment. A significant decrease in serum IgG levels after initiation of bortezomib treatment was observed in all patients, five of them (41.6%) showed hypogammaglobulinemia (<500 mg/dl), but no patient suffered from opportunistic infections; in only two patients (16.6%) hypogammaglobulinemia persisted at the end of follow-up. Two patients (16.6%) suffered from sensory neuropathy, which led to bortezomib treatment discontinuation. Conclusions Bortezomib may be an effective option for refractory LN, but close monitoring must be performed for possible adverse events such as peripheral neuropathy and hypogammaglobulinemia.

P0451TEN-YEAR OUTCOME DIFFERENCES IN LUPUS NEPHRITIS PATIENTS TREATED WITH CYCLOPHOSHAMIDE AND MYCOPHENOLATE- BASED TREATMENT REGIMEN

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Narayan Prasad ◽  
Jithu Kurian ◽  
Vikas Agarwal ◽  
Dharmendra Bhadauria ◽  
Amit Gupta
Keyword(s):  
Lupus Nephritis ◽  
Serum Creatinine ◽  
Cause Of Death ◽  
Patient Survival ◽  
Class Iii ◽  
Renal Survival ◽  
Common Cause ◽  
Class Iv

Abstract Background and Aims Lupus nephritis (LN) poses a considerable impact on the morbidity and mortality of SLE patients. Long term comparative outcome data with cyclophosphamide (CYP) and mycophenolate mofetil (MMF) based regimen from the Indian subcontinent is sparse. We assessed the renal and patient survival of these patients for the types of induction CYP or MMF and the two maintenance therapies – MMF or Azathioprine. We determined the predictors of death and dialysis dependency in the study population. Method In this retrospective study, we analysed outcomes of 100 LN patients, total 67 (26 class III, 25 class IV, 6 class III+V, and 10 class IV+V)) treated with CYP (euro lupus-40 and NIH- Dharmendra Bhadauria 27), and 33 with MMF based regimen with the steroid between July 2008 to June 2018. The class distribution of the patients in the two groups was similar. The data were archived regarding demography, clinical, histopathological features, and the treatment given of all 100 biopsy-proven LN patients. Outcomes between two regimens CYP and MMF in terms of remission, dialysis dependency, and patient survival were compared. The renal survival and patient survival at the end of follow-up between two groups were also analysed. Results The clinical characteristics were similar in both groups, except the activity index was high in CYP patients (6.13 ±4.48 Vs. 4.61 ± 2.80); however, the chronicity index was similar. The overall remission was 70% at the end of induction. The CR, PR, and NR in the CYP group was 46.2%, 23.9 %, 29.9% respectively; however, in the MMF group was 57.6%, 12.1%, and 30.3%, respectively. More patients died in CYP (14.9%) than those in MMF (9.1 %) patients. The 1-, 2-, 3-, 4-, 5- and 10-years patient survival in the CYP induction was 89.5%, 86.2%, 86.2%,83.8%, 83.8% and 83.8% however in MMF was 93.9%, 93.9%, 89%, 89%, 89% and 89% respectively. The most common cause of death was sepsis 9/13(69.2%), followed by uremia. The high serum creatinine, low Hb, male, thrombocytopenia, microscopic haematuria, leukocyturia, nephrotic proteinuria, lack of remission in 12 months, dialysis, doubling of creatinine on follow-up were significant predictors of mortality. The 1-, 2- 3-, 4-, 5- and 10- years renal survival (event death-censored, but dialysis dependency) in CP group was 98.5%, 96.7%, 94.7%, 92.4%, 92.4% and 84 % respectively however in the MMF was 96.8 %, 96.8%, 91.9%, 91.9%, 91.9%, and 78.8% respectively. (Figure 1)At the end of the study, dialysis dependency in the MMF group and CYP group was 7.5% and 12.1 %, respectively (NS). In the maintenance therapy, 3/56(5.3%) had to double of creatinine in MMF, and 7/34 (20.5%) in the AZA group (p=0.03). Conclusion Long term outcomes in terms of patient and renal survival of LN patients treated with CP and MMF based induction is similar. Serum creatinine doubling was more with MMF than AZA based maintenance. The majority of death occurred during induction, and sepsis was the most common cause of death.

Cyclosporine & Mycophenolate Mofetil in the Treatment of Cyclophosphamide Refractory Class-IV Lupus Nephritis

1970 ◽  
Vol 5 (2) ◽  
pp. 8-13
Author(s):  
M Mostafi ◽  
MG Rabbani ◽  
MR Hossain ◽  
AR Siddiqui ◽  
SB Rabbani
Keyword(s):  
Mycophenolate Mofetil ◽  
Lupus Nephritis ◽  
Lupus Erythematosus ◽  
Activity Index ◽  
Remission Rate ◽  
Disease Activity Index ◽  
Military Hospital ◽  
One Year ◽  
Class Iv

Class IV Lupus Nephritis is a difficult medical situation requiring aggressive management. Many patients do not respond to conventional cyclophosphamide (CPM) therapy. The aim of this study was to evaluate the effect of cyclosporine (CsA) and mycophenolate mofetil (MMF) in the treatment of CPM refractory class IV Lupus nephritis. The study was conducted at Combined Military Hospital (CMH) and Cantonment General Hospital (CGH) of Dhaka over a period of 8 years (from January 2000 till December 2008). CPM refractory Class IV Lupus nephritis patients were randomly assigned into 2 groups cyclosporine (4mg/kg/day) and mycophenolate mofetil (1000-2000mg/day). Thirty one patients completed at least one year follow up and were included in the study. Sixteen patients were included in cyclosporine group and 15 patients in mycophenolate mofetil group. CsA treated patients had a remission rate of 87.5% which was 80% in MMF group. The average remission time was 16.21 weeks in CsA and 20.91 weeks in MMF group. The urinary total protein(UTP) and creatinine clearance (CCr) values  were  similar in both groups, 0.54 gm vs 0.66 gm & 81 vs 86 ml/min. The systemic lupus erythematosus disease activity index (SLEDAI) was 9.56 and 9.2 in CsA and MMF group which came down to 1.92 and 1.83 in the same groups after remission. In this study It was found that both cyclosporine and mycophenolate mofetil were very effective in the treatment of CPM refractory class IV Lupus nephritis with slight better response with cyclosporine. Key words: Lupus Nephritis, mycophenolate mofetil, cyclosporine. DOI: 10.3329/jafmc.v5i2.4575 JAFMC Bangladesh Vol.5(2) (December) 2009, pp.8-13

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