Metalloproteins structural and functional insights into immunological patterns.

Metalloproteins play a crucial role in regulating different aspects of the immune system in humans. They have various functions in immunity, including recognizing and presenting antigens, aiding in the movement and effectiveness of immune cells, and facilitating interactions between the host and pathogens. Understanding how these proteins work can help us develop new methods to control the immune response in different diseases. Metalloproteins contain metal ions in their structure, which allows them to perform these diverse functions. They encompass a wide range of enzymes, signaling molecules, and structural proteins that utilize metal ions as cofactors for their activities. Examples of metalloproteins include superoxide dismutase, catalase, and metalloproteases, which regulate oxidative stress, inflammation, and tissue remodelling processes associated with immune activation. By studying their functions and the effects of their dysfunction, researchers can develop strategies to improve immune function and combat various diseases. This review explores the diverse functions of metalloproteins in immune processes, highlighting their significance in both health and disease.

Green synthesis of silver nanoparticle prepared with Ocimum species and assessment of anticancer potential.

Silver nanoparticles (AgNPs) have gained much attention due to their unique physical, and chemical properties. Integration of phytochemicals in nanoformulation might have higher applicability in healthcare. Current work demonstrates the synthesis of green AgNPs with O. gratissimum (gr-AgNPs) O. tenuiflorum (te-AgNPs) and O. americanum (am-AgNPs) followed by an evaluation of their antimicrobial and anticancer properties. SEM analysis revealed spherical-shaped particles with average particle sizes of 69.0 ± 5 nm for te-AgNPs, 46.9 ± 9 nm for gr-AgNPs, and 58.5 ± 18.7 nm for am-AgNPs with a polydispersity index below 0.4. The synthesized am-AgNPs effectively inhibited Klebsiella pneumonia, Escherichia coli, Staphylococcus aureus, Aspergillus niger, and Candida albicans with 23 ± 1.58 mm, 20 ± 1.68 mm, 22 ± 1.80 mm, 26 ± 1.85 mm, and 22 ± 1.40 nm of zone of inhibition respectively. Synthesized AgNPs also induced apoptotic cell death in MCF-7 in concentration-dependent manner. IC50 values for am-AgNPs, te-AgNPs, and gr-AgNPs were 14.78 ± 0.89 µg, 18.04 ± 0.63 and 15.41 ± 0.37 µg respectively which suggested that am-AgNPs were the most effective against cancer. At higher dose size (20 µg) AgNPs were equally effective to commercial standard Doxorubicin (DOX). In comparison to te-AgNPs and gr-AgNPs, am-AgNPs have higher in vitro anticancer and antimicrobial effects. The work reported Ocimum americanum for its anticancer properties with chemical profile (GCMS) and compared it with earlier reported species. The activity against microbial pathogens and selected cancer cells clearly depicted that these species have distinct variations in activity. The results have also emphasized on higher potential of biogenic silver nanoparticles in healthcare but before formulation of commercial products, detailed analysis is required with human and animal models.

Evaluation of the toxicological properties of Himantura imbricata Venom using a zebrafish model (Danio rerio).

The stingrays of the genus Himantura imbricata are present in all of the world's oceans, but the toxicity of their venoms has not yet been thoroughly characterized. The zebrafish as a toxicology model can be used for general toxicity testing of drugs and the investigation of toxicological mechanisms. The aim of this study was to evaluate the effect of crude venom from the stingray H. imbricata on the zebrafish Danio rerio. Juvenile zebrafish were injected with different concentrations of venom from H. imbricata via subcutaneous injections. The venom's effects were established via histological examination and hemolytic activity in zebrafish. The histopathological analysis revealed significant tissue damage in the organs of the zebrafish injected with venom, including liver necrosis and kidney degeneration. A blood examination revealed echinocytes, hemolysis, and nuclear abnormalities. Bodyweight estimations and histopathological attributes of the gills, heart, muscle, liver, intestine, eye, and brain were determined. The histological staining studies of the gills, liver, and intestine were measurably higher in the venom groups compared with the other two groups. Aggregately, the result shows that zebrafish may act as a valuable biomarker for alterations impelled by H. imbricata venom. The work delivers a useful model with substantial pharmacological potential for new drugs and a better comprehension of research on stingray venom.

Exposure to ambient air pollution and autoantibody status in rheumatoid arthritis.

OBJECTIVE: To evaluate the relationship between air pollutant (AP) exposure and rheumatoid arthritis (RA) autoantibody status METHODS: We performed a cross sectional study utilizing enrollment data from participants in the Veterans Affairs rheumatoid arthritis registry. HLA-DRB1 shared epitope (SE), smoking, rheumatoid factor (RF), and anti-cyclic citrullinated peptide antibody (ACPA) status were collected. Mean exposure levels were obtained for AP (NO2, SO2, particulate matter [PM2.5, PM10], and ozone) from air quality monitoring stations at patients' residential zip codes in the year prior to enrollment. Multivariable logistic and ordinary least squares regression models were used to determine independent associations of AP with RA seropositivity and autoantibody concentration. RESULTS: The cohort included 557 veterans (90% male, 76% Caucasian), with mean age of 70 years and mean disease duration of 13 years. The majority were HLA-DRB1 SE, RF, and ACPA positive (73%, 79%, and 76%, respectively). In univariate models, PM2.5 exposure was associated with higher ACPA concentration (p = 0.009). Similarly, in multivariable regression models, PM2.5 exposure was independently associated with higher ACPA concentration (p = 0.037). Current smoking independently predicted RF and ACPA positivity and titers, while HLA-DRB1 SE alleles were associated with RF positivity and ACPA positivity and titers. CONCLUSIONS: In an elderly cohort of RA patients, fine particulate matter (PM2.5) exposure independently predicted higher ACPA concentration. Further study of fine particulate matter in the pathogenesis of RA is warranted. Key Points • A study that integrates both genetic and environmental exposure data, relative to RA autoantibody status. • Of different air pollutants measures, exposure to fine particulate matter (PM2.5) appears to be most closely linked to ACPA titers.

Evaluation of cytokine profiles in rheumatoid arthritis patients with clinically active disease and normal inflammatory indices.

OBJECTIVE: To assess the potential utility of a cytokine measurement in rheumatoid arthritis (RA) patients with active joint disease but normal acute phase reactants (APR). METHODS: RA patients in a longitudinal observational registry with available cytokine array data were included. Patients were categorized based on agreement/disagreement of physical examination and APR measurements: concordant high (CH) [high tender and/or swollen joint counts (TJC + SJC > 3) and APR (ESR ≥ 28 mm/h + CRP ≥ 1.5 mg/L)]; concordant low (CL) [TJC + SJC ≤ 3 and normal APR]. Discordant (D) [TJC + SJC > 3 and normal APR] patients were stratified into low, medium, and high-disease activity (DL, DM, DH). Weighted-average and log-transformed cytokine scores were calculated based on results of a cytokine array. Chi-square tests compared categorical variables by concordance status; t tests, Wilcoxon rank-sum tests, ANOVA models, and ordinary least squares (OLS) regressions were used to compare continuous measures. RESULTS: RA patients (n = 1467) were predominantly male (91%). Compared to CH patients (n = 174), D (n = 434) were younger, less frequently seropositive, with lower TJC, SJC, and DAS28-3v scores (p < 0.001). Cytokine scores for DL, DM, and DH groups were lower than CH patients (p < 0.001) and did not differ between DL, DM, and DH subgroups and were similar to CL (n = 356) patients. In multivariable analyses including CH and D patients, log-cytokine score was associated with higher DAS28-3v scores (p = 0.029). In multivariable analyses including CL patients, concordance status (p = 0.011) and ACPA (p = 0.013) were predictors of higher log cytokine score. CONCLUSION: In this study, cytokine scores did not identify active joint disease in RA patients with normal APR.

Plausible Role of Acute HIV Infection Mediated Immune Activation in Causing Renal Allograft Rejection: A Case Report.

Current research states that AIDS pathogenesis has its roots in a chronic activation of immune system secondary to human immunodeficiency virus (HIV)-induced proliferation of T cells, B cells, NK cells, and macrophages. Immune activation due to acute HIV infection can be highly detrimental to allograft survival in a renal transplant recipient. In this report, we describe a 32-year-old African-American male patient who underwent a second live donor renal transplant, following which he developed acute allograft rejection coincident with newly acquired HIV seropositivity.

Type VI Choledochal Cyst-An Unusual Presentation of Jaundice.

Choledochal cysts involving the cystic duct are extremely rare, and are usually associated with cystic dilatations of the extrahepatic biliary tract. We describe a patient who presented with jaundice and was found to have a dilatation of the common bile duct on computed tomographic imaging, consistent with a choledochal cyst. He underwent a laparoscopic-converted-to-open cholecystectomy with excision of the choledochal cyst which was found to involve the cystic duct. Choledochal cysts involving the cystic duct are notably missing from the Todani classification. Although exceedingly rare, new cases of these types of cysts are being reported, in part due to advancement of diagnostic imaging modalities. We discuss the current classification scheme for choledochal cysts and we propose an expansion of this scheme.

Recipient Criteria Predictive of Graft Failure in Kidney Transplantation.

Several classifications systems have been developed to predict outcomes of kidney transplantation based on donor variables. This study aims to identify kidney transplant recipient variables that would predict graft outcome irrespective of donor characteristics. All U.S. kidney transplant recipients between October 25,1999 and January 1, 2007 were reviewed. Cox proportional hazards regression was used to model time until graft failure. Death-censored and nondeath-censored graft survival models were generated for recipients of live and deceased donor organs. Recipient age, gender, body mass index (BMI), presence of cardiac risk factors, peripheral vascular disease, pulmonary disease, diabetes, cerebrovascular disease, history of malignancy, hepatitis B core antibody, hepatitis C infection, dialysis status, panel-reactive antibodies (PRA), geographic region, educational level, and prior kidney transplant were evaluated in all kidney transplant recipients. Among the 88,284 adult transplant recipients the following groups had increased risk of graft failure: younger and older recipients, increasing PRA (hazard ratio [HR],1.03-1.06], increasing BMI (HR, 1.04-1.62), previous kidney transplant (HR, 1.17-1.26), dialysis at the time of transplantation (HR, 1.39-1.51), hepatitis C infection (HR, 1.41-1.63), and educational level (HR, 1.05-1.42). Predictive criteria based on recipient characteristics could guide organ allocation, risk stratification, and patient expectations in planning kidney transplantation.

Effects of Parvovirus B19 Infection in Renal Transplant Recipients: A Retrospective Review of Three Cases.

Parvovirus B19 (PVB19) is a DNA virus which causes clinically relevant infection in renal transplant recipients (RTR) leading to significant morbidity. Manifestations include erythropoietin resistant anemia, proteinuria, and glomerulosclerosis in the allograft. Severe infection may require administration of intravenous immunoglobulin, reduction in immunosuppression and transfusions. The major challenge in managing and preventing the infection in RTR involves the act of balancing the decreased level of immunosuppression and the risk of rejection. The objective of this article is to understand the importance of PVB19 infection and its outcome in RTR. We reviewed the medical records of three RTR with confirmed PVB19 infection and recorded patient information including demographics, clinical and laboratory data, management, and outcome. The average time of occurrence of PVB19 infection as transplant was 8.6 weeks and they presented with symptomatic anemia. Elevated creatinine values were noted in two of them. Following treatment, anemia improved and creatinine values returned to baseline. One of them developed an early relapse and had to be treated once again similarly. We emphasize the importance of maintaining a high index of suspicion for PVB19 infection in patients with anemia in the posttransplant phase, especially in patients on higher doses of immunosuppressants. Early and proper treatment can prevent worsening clinical condition and possible effects on the allograft.

An analysis of pancreas transplantation outcomes based on age groupings--an update of the UNOS database.

INTRODUCTION: Previously, increasing age has been a part of the exclusion criteria used when determining eligibility for a pancreas transplant. However, the analysis of pancreas transplantation outcomes based on age groupings has largely been based on single-center reports. METHODS: A UNOS database review of all adult pancreas and kidney-pancreas transplants between 1996 and 2012 was performed. Patients were divided into groups based on age categories: 18-29 (n = 1823), 30-39 (n = 7624), 40-49 (n = 7967), 50-59 (n = 3160), and ≥60 (n = 280). We compared survival outcomes and demographic variables between each age grouping. RESULTS: Of the 20 854 pancreas transplants, 3440 of the recipients were 50 yr of age or above. Graft survival was consistently the greatest in adults 40-49 yr of age. Graft survival was least in adults age 18-29 at one-, three-, and five-yr intervals. At 10- and 15-yr intervals, graft survival was the poorest in adults >60 yr old. Patient survival and age were found to be inversely proportional; as the patient population's age increased, survival decreased. CONCLUSION: Pancreas transplants performed in patients of increasing age demonstrate decreased patient and graft survival when compared to pancreas transplants in patients <50 yr of age.

Extended-spectrum-beta-lactamase producing bacteria related urinary tract infection in renal transplant recipients and effect on allograft function.

BACKGROUND: Urinary tract infection (UTI) is a well-recognized early complication in renal transplant recipients (RTR) and can have significant bearing on their outcome. The recent rise in incidence of extended spectrum beta lactamase (ESBL) producing bacteria causing UTI among RTR poses new and significant challenges in terms of management and outcome. Our aim is to analyze the effect of ESBL producing bacteria causing UTI in these patients and its impact on allograft function. METHODS: We reviewed the medical records of 147 RTR who were followed at a tertiary care hospital affiliated transplant center between January 2007 and May 2013 and noted five RTR who developed episodes of ESBL producing bacteria related UTI during follow up. Multiple patient characteristics including demographics, immunosuppression, recurrences, allograft function and outcome were analyzed. RESULTS: Five patients (3.4%) out of 147 had ESBL producing bacteria related UTI. We found all patients to be above 60 years of age, with three out of five being females, and all five patients had diabetes mellitus. We identified a total of 37 episodes of UTI among these five patients during this period. Two of these patients had elevated creatinine values during the episodes of UTI and three of them developed bacteremia. Of the five patients, four of them had a favorable outcome except for one patient who developed persistent allograft dysfunction. CONCLUSION: RTR are at a higher risk for developing ESBL producing bacteria associated UTI. Early diagnosis along with appropriate and judicious use of antibiotics will ensure long term success in allograft and patient outcome.

Pancreas transplantation from donors after cardiac death: an update of the UNOS database.

OBJECTIVE: There is reluctance to use donation after cardiac death (DCD) organs for fear of worse outcomes due to increased warm ischemia time. Extensive evidence to confirm the quality of DCD pancreas transplants is not manifest. METHODS: A united network for organ sharing database review of pancreas transplants performed between 1996 and 2012 was conducted. We compared outcomes and all demographic variables between donors after cardiac death and donors after brain death in pancreas transplantation. RESULTS: There were 320 DCD pancreas transplants and 20,448 donation after brain death pancreas transplants performed in the United States between 1996 and 2012. There was no statistically significant difference in graft survival or patient survival in pancreas transplantation in DCD versus donation after brain death donors measured at 1-year, 3-year, 5-year, 10-year, and 15-year intervals. There was no significant difference between donor and recipient age, race, sex, and body mass index (BMI) between the groups. There was no significant difference between the recipient ethnicity or time on wait list between the groups. CONCLUSIONS: Pancreata procured by DCD have comparable outcomes to those procured after brain death. Donation after cardiac death pancreas transplant is a viable method of increasing the donor pool, decreasing wait list mortality, and improving the quality of life for type 1 diabetic patients.

Factors associated with completion of pre-kidney transplant evaluations.

This study sought to examine various factors that may prevent transplant candidates from completing their transplant workup prior to listing. We reviewed the records of 170 subjects (cases = 100, controls 70) who were either on dialysis or had less than 20 mL/min creatinine clearance and were therefore candidates for preemptive transplantation. Approximately, 56% of preemptive patients completed their workup, while only 36% of patients on dialysis completed their workup. Our data revealed that factors contributing toward completion of workup included intrinsic motivation (four times more likely), lack of specific medical comorbidities (three times more likely), and preemptive status (two times more likely). Among patients on dialysis, intrinsic motivation (five times more likely) and absence of cardiovascular complications (four times more likely) were associated with completion. When comparing patients on dialysis to patients not on dialysis, there were significant differences between the two groups in distance from home to the transplant center, level of education, and presence of medical comorbidities. We believe that targeted interventions such as timely referral, providing appropriate educational resources, and development of adequate support systems, have the potential to improve workup compliance of patients with advanced chronic kidney disease, including those on dialysis.

Forty-eight hour kidney transplant admissions.

Forty-eight hour kidney transplantation admissions are a feasible option in selected recipients of live-donor allografts through the use of standardized post-operative protocols, multidisciplinary team patient care, and intensive follow-up at outpatient centers. Age, gender, and pre-transplant dialysis status did not impact the ability to achieve 48-hour admissions. We did not identify any other pre-operative risk factors that contributed to increased length of stay. Although ABO and highly sensitized recipients had longer lengths of stay, the subgroup was too small to achieve statistical significance. We did not encounter any readmissions within the first seven post-operative days. Further improvements in clinical management will enhance the potential to shorten the length of hospital stay for all kidney transplant recipients.

Significance of elevated transplant renal artery velocities in the postoperative renal transplant patient.

INTRODUCTION: Non-invasive imaging studies can provide visualization of allograft perfusion in the postoperative evaluation of newly transplanted renal allografts. AIM: The purpose of our study was to evaluate the significance of elevated renal artery velocities in the immediate postoperative period. METHODS: Peak systolic velocities (PSVs) were obtained in the transplanted renal artery of 128 patients immediately after transplantation. Repeat allograft Doppler ultrasonography was performed on patients with elevated values. RESULTS: Of the 128 patients, 57 (44.5%) had severely elevated Doppler velocities >400 cm/s on the initial studies. Three patients within this category had persistently elevated values of >400 cm/s, warranting angiographic visualization of the renal vessels. Stent placement within the transplanted renal artery was required in two of these patients. There was normalization of the PSV in the remaining patients. CONCLUSIONS: Routine allograft Doppler ultrasonography in the immediate postoperative period allows for visualization of allograft perfusion. Elevated renal artery velocities in the immediate postoperative period do not necessarily represent stenosis requiring intervention. Failure of the PSV to normalize may require further intervention, and angiography continues to be the gold standard.

Shortened length of stay improves financial outcomes in living donor kidney transplantation.

Kidney transplantation is the preferred clinical and most cost-effective option for end-stage renal disease. Significant advances have taken place in the care of the transplant patients with improvements in clinical outcomes. The optimization of the costs of transplantation has been a constant goal as well. We present herein the impact in financial outcomes of a shortened length of stay after kidney transplant.

Lack of protective efficacy in buffaloes vaccinated with Fasciola gigantica leucine aminopeptidase and peroxiredoxin recombinant proteins.

Gene coding for leucine aminopeptidase (LAP), a metalloprotease, was identified in the tropical liver fluke, Fasciola gigantica; that on sequence analysis showed a close homology (98.6%) with leucine aminopeptidase of the temperate liver fluke, Fasciola hepatica. The recombinant leucine aminopeptidase protein was expressed in Escherichia coli. F. gigantica peroxiredoxin, a hydrogen peroxide scavenger and an immunomodulating protein, was also cloned and expressed in E. coli. A vaccination trial in buffaloes was conducted with these two recombinant proteins, with 150 and 300 µg of leucine aminopeptidase and a cocktail of 150 µg each of recombinant leucine aminopeptidase and peroxiredoxin in three groups, respectively. Both Th1- and Th2-associated humoral immune responses were elicited to immunization with these antigens. A challenge study with 400 metacercariae did not show a significant protection in terms of reduction in the worm burden (8.4%) or anti-fecundity/embryonation effect in the immunized groups, as to the non-immunized control animals. Our observations in this buffalo vaccination trial are contrary to the earlier promise shown by leucine aminopeptidase of F. hepatica as a leading candidate vaccine molecule. Identification of leucine aminopeptidase gene and evaluation of the protein for its protective efficacy in buffaloes is the first scientific report on this protein in F. gigantica.