Seroprevalence and trends of transfusion transmissible infections among retrospective blood donors in Western Azerbaijan Regional Blood Transfusion Center,Iran: A ten-years evaluation

Transfusion transmissible infections (TTIs) have been a public health challenge for the accessibility, quality and safety of blood transfusion. The present study aimed to consider the prevalence and the trends of hepatitis B virus (HBV), hepatitis C virus (HCV), Human T-cell leukemia virus type 1 (HTLV-1), human immunodeficiency virus (HIV) and syphilis across the ten years among retrospective blood donors. A retrospective investigation of blood donors’ data covering the period from 22 May 2009 to 22 May 2019 was done. Data was accumulated and analyzed from Blood Transfusion Center records, pertaining to all donors who were screened for various TTIs using respective immunological techniques. Out of the 682,171 screened donors in the 2009–2019 study period, 2470 (0.36 %) were infected with at least one infectious agent. The overall prevalence of HBV, HCV, HTLV-1, HIV and syphilis were 1700 (0.25 %), 184 (0.027 %), 335 (0.05 %), 4 (0.0.05 %) and 247 (0.036 %), respectively. The study showed male dominated donor pool (96.79 %) with higher prevalence (0.34 %) of TTIs compared to female donors (0.02 %) with 3.21 % population. Despite the low prevalence of TTIs in our study, HBV, HCV, syphilis and HIV have remained a big threat to safe blood transfusion in Iran. Strict adherence to selection criteria, algorithm of donor screening, use of highly sensitive and specific methods for detection of TTIs, regular consultation and health education programs, prevention and sanitization strategies to reduce the risk of TTIs are recommended to reduce the risk of TTIs and ensure the safety of blood transfusion for recipient.     

Early Transplant Arteriopathy in Kidney Transplantation

BackgroundEarly dysfunction of renal allografts may be associated with vascular injury, which raises the specter of active rejection processes that require medical intervention. In our practice, we have encountered patients who present with delayed graft function and demonstrate a unique pattern of endothelial cell injury that raises concern for rejection in their biopsy. Therefore, we sought to systematically determine the biopsy characteristics and outcome of these patients.MethodsDuring a 17-year period at the University of Washington in Seattle, United States, we identified 24 cases of a distinct arterial vasculopathy presenting in the first year posttransplantation. This early transplant arteriopathy (ETA) is characterized by endothelial cell swelling and intimal edema but without the intimal arteritis that defines vascular rejection.ResultsApproximately 1% of transplant biopsies during the study period showed ETA, almost all of which were in deceased donor organs (96%), and most presented with delayed graft function (54%) or increased serum creatinine (38%) soon after transplantation (median 13 days; range, 5-139). In this study, 77% of patients were managed expectantly, with only 2 patients (7.6%) subsequently developing acute vascular rejection. Except for 1 patient who died, all patients had functioning allografts at 1 year follow-up.ConclusionRecognizing ETA and distinguishing it from vascular rejection is important to prevent over-treatment because most patients appear to recover allograft function rapidly with expectant management.     

NH4+ secretion in inner medullary collecting duct in potassium deprivation: role of colonic H+-K+-ATPase

NH4+ secretion in inner medullary collecting duct in potassium deprivation: Role of colonic H+-K+-ATPase. BACKGROUND: In K+ deprivation (KD), gastric (g) H+-K+-ATPase (HKA) is suppressed, whereas colonic (c) HKA is induced in the terminal inner medullary collecting duct (IMCD). We hypothesized that in KD, cHKA is induced and can mediate the secretion of NH4+. METHODS: Rats were sacrificed after 2, 3, 6, or 14 days on regular (NML) or K+-free (KD) diet. mRNA expression of HKA isoforms in terminal inner medulla was examined and correlated with NH4+ secretion in perfused IMCD in vitro. RESULTS: Urinary NH4+ excretion increased after K+-free diet for six days. In terminal inner medulla, cHKA expression was strongly induced, whereas gHKA expression was decreased. NH4+ secretion increased by 62% in KD (JtNH4+ 0.57 vs. 0.92 pmol/min/mm tubule length, P < 0.001). Ouabain (1 mM) in perfusate inhibited NH4+ secretion in KD by 45% (P < 0.002) but not in NML. At luminal pH 7.7, which inhibits NH3 diffusion, NH4+ secretion in IMCD was 140% higher in KD (0.36 vs. 0.15, P < 0.03) and was sensitive to ouabain. ROMK-1 mRNA expression was induced in parallel with cHKA in inner medulla. CONCLUSIONS: These data suggest that in KD, cHKA replaces gHKA and mediates enhanced secretion of NH4+ (and H+) into the lumen facilitated by K+ recycling through ROMK-1.     

Glucocorticoids enhance the expression of the basolateral Na+:HCO3- cotransporter in renal proximal tubules

BACKGROUND: Studies have shown that glucocorticoids enhance HCO3- reabsorption in proximal tubules. Functional and molecular studies indicate that HCO3- reabsorption in proximal tubules is mediated via luminal H(+)-ATPase and Na+/H+ exchanger (NHE-3), and basolateral Na+:HCO3- cotransporter (NBC) acting in series. The purpose of these experiments was to examine the effect of adrenal steroids on NBC-1 and NHE-3 expression and activity in rat renal proximal tubules. METHODS: Rats were injected subcutaneously with dexamethasone (100 mu/day) or deoxycorticosterone acetate (30 mg/kg), potent glucocorticoid, or mineralocorticoid analogues, respectively. Animals were sacrificed after two or four days, and NBC-1 and NHE-3 mRNA expression and activities were measured in cortex and proximal tubules. RESULTS: Northern hybridizations indicated that cortical NBC-1 mRNA expression increased by approximately 92% in rats treated with dexamethasone for four days (N = 6, P < 0.03) but not two days. NHE-3 mRNA expression remained unchanged. NBC and NHE-3 activities were measured as the Na-dependent pHi recovery from an acid load in the presence or absence of HCO3-, respectively, and appropriate inhibitors in proximal tubule suspensions loaded with BCECF. NBC activity increased by approximately 80% in rats treated with dexamethasone for four days (P < 0.01, N = 5) but not two days. NHE-3 activity increased by 34 and 42% in rats treated with dexamethasone for two and four days, respectively (P < 0.05 and P < 0.02 for each group vs. control). Treatment with deoxycorticosterone acetate did not alter NBC-1 expression. CONCLUSION: Glucocorticoids at pharmacologic concentrations enhance the mRNA expression and functional activity of renal proximal tubule NBC-1. Enhanced NBC and NHE-3 activities could result in increased HCO3- reabsorption in proximal tubule and could contribute to the maintenance of metabolic alkalosis in pathophysiologic states associated with increased glucocorticoid production.     

Multimodal imaging in photic retinopathy

Letter to the Editor     

Immune checkpoints in targeted-immunotherapy of pancreatic cancer: New hope for clinical development

Immunotherapy has been recently considered as a promising alternative for cancer treatment. Indeed, targeting of immune checkpoint (ICP) strategies have shown significant success in human malignancies. However, despite remarkable success of cancer immunotherapy in pancreatic cancer (PCa), many of the developed immunotherapy methods show poor therapeutic outcomes in PCa with no or few effective treatment options thus far. In this process, immunosuppression in the tumor microenvironment (TME) is found to be the main obstacle to the effectiveness of antitumor immune response induced by an immunotherapy method. In this paper, the latest findings on the ICPs, which mediate immunosuppression in the TME have been reviewed. In addition, different approaches for targeting ICPs in the TME of PCa have been discussed. This review has also synopsized the cutting-edge advances in the latest studies to clinical applications of ICP-targeted therapy in PCa.KEY WORDS: Immune checkpoint, Pancreatic cancer, Tumor microenvironment, Immunotherapy, Clinical development     

Delivery of Exogenous miR-124 to Glioblastoma Multiform Cells by Wharton’s Jelly Mesenchymal Stem Cells Decreases Cell Proliferation and Migration,and Confers Chemosensitivity

MicroRNAs (miRs) are potential therapeutic targets in glioblastoma multiforme (GBM), but the difficulties associated with their delivery to tumor target cells have hampered their widespread use. Mesenchymal stem cells (MSCs) can migrate to the sites of cancers, including GBM and exert anti-tumor effects. In this study, it is shown that Wharton’s jelly-MSCs (WJ-MSCs) have the ability to deliver exogenous miRs to GBM cells and the functional impact of this delivery is characterized. It is found that the labeled miR-124, as an example for miR of interest, can be successfully delivered with WJ-MSCs to U87 GBM cells via dependent or exosome-independent processes. It is demonstrated that the delivered exogenous miR-124 significantly decreases the luciferase activity of the target gene CDK6. In addition, the delivered miR-124 enhances the chemosensitivity of GBM cells to temozolomide and decreases the migration of GBM cells. These results suggest that the use of exogenous miRNA delivery with the derived exosomes from WJ-MSCs may provide a novel approach for miRNA replacement therapy in GBM cancers.