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A newly identified virus appeared in Wuhan, China, in December 2019, was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and caused the coronavirus disease 2019 (COVID-19). SARS-CoV-2 presents similarities with two previous coronavirus pandemics, MERS (Middle East Respiratory Syndrome) and SARSCoV, concerning phylogenetic origin, structural composition, and clinical symptoms, thus, leading to common pathogenic mechanisms. The purpose of this review is to declare the role of interleukin-6 (IL-6) in the pathogenesis, prognosis, and treatment of COVID-19 by comparing its effect on SARS-CoV and MERS cases. Increased levels of IL-6 comprise the key for the stimulation of cytokine storm and the progression of SARS, MERS, and COVID-19 cases. Especially, in COVID-19 patients, the overactivation of NF-k, which is caused by the binding of coronavirus spike protein S to alveolar epithelial cells, up-regulates IL-6 and promotes its systematic circulation, causing alveolar damage and extrapulmonary injury. Additionally, IL-6 can be used to evaluate respiratory failure and identify asymptomatic patients. Tocilizumab (TCZ), a monoclonal antibody which blocks IL-6 signaling, comprises a remedial option against COVID-19. TCZ improves oxygenation, reduces fever, and decreases levels of IL-6. IL-6 plays a major role in the pathogenesis of cytokine storm and the progression of COVID-19 and may be used as a therapeutic target against COVID-19. However, further research is needed concerning the relation of IL-6 in COVID-19 cases, and more clinical trials are required to declare TCZ as a treatment option.

Chronic Kidney Disease (CKD) is characterized by immune activation with development of chronic inflammation. However, immune deficiency also exists in CKD patients. The number and the activity of Natural Killer cells (NK-cells) are influenced by the biocompatibility of various dialysis membranes. In this study we investigated the effect of dialysis modality and membrane type on NK-cell number and on phagocytic activity of neutrophils in patients on different dialysis methods.

Transforming growth factor-beta(1) (TGF-beta(1)) is the major fibrogenic growth factor implicated in the pathogenesis of renal scarring. Proteinuria is a poor prognostic feature for various types of glomerular disease and its toxic action may be related to the activation of tubular epithelial cells towards increased production of cytokines and chemoattractant peptides. In this work we studied the site of synthesis and expression profile of TGF-beta(1) in the renal tissue of patients with heavy proteinuria and examined the relation of this expression with the urinary excretion of TGF-beta(1).

Background. Transforming growth factor‐β1 (TGF‐β1) is the major fibrogenic growth factor implicated in the pathogenesis of renal scarring. Proteinuria is a poor prognostic feature for various types of glomerular disease and its toxic action may be related to the activation of tubular epithelial cells towards increased production of cytokines and chemoattractant peptides. In this work we studied the site of synthesis and expression profile of TGF‐β1 in the renal tissue of patients with heavy proteinuria and examined the relation of this expression with the urinary excretion of TGF‐β1.Methods. Twenty‐five patients with heavy proteinuria (8.4±3.0 g/24 h) were included in the study. All patients underwent a diagnostic kidney biopsy and were commenced on immunosuppressive therapy with corticosteroids and cyclosporin. The sites of synthesis and expression profile of TGF‐β1 mRNA and protein in the kidney were examined by in situ hybridization and immunohistochemistry. Urinary and plasma TGF‐β1 levels were determined by ELISA before the initiation of treatment and 6 months later and compared with those of normal subjects and of patients with IgA nephropathy and normal urinary protein excretion.Results. The site of synthesis and expression of TGF‐β1 in the renal tissue of patients with heavy proteinuria was mainly localized within the cytoplasm of tubular epithelial cells. Interstitial expression was also present but glomerular TGF‐β1 expression was found only in patients with mesangial proliferation. Urinary TGF‐β1 excretion was significantly higher in nephrotic patients compared with normal subjects and with patients with IgA nephropathy and normal urinary protein excretion (783±280 vs 310±140 and 375±90 ng/24 h, respectively; P<0.01). In patients with remission of proteinuria after immunosuppressive therapy, urinary TGF‐β1 excretion was significantly reduced (from 749±290 to 495±130 ng/24 h; P<0.01), while in patients with persistent nephrotic syndrome, it remained elevated.Conclusions. The localization of TGF‐β1 mRNA and protein within tubular epithelial cells, along with its increased urinary excretion in patients with nephrotic syndrome, suggest the activation of these cells by filtered protein towards increased TGF‐β1 production.

Background/Aims:The pathophysiological pathways involved in the pathogenesis and evolution of renal fibrosis, have not been fully elucidated. Transforming growth factor-beta1 (TGF-β1) is involved in the development of renal scarring. Apoptosis is responsible for intrinsic cell deletion observed in end-stage kidney disease. Myofibroblasts are involved in the development of renal fibrosis. This study investigates whether there is a potential relationship between apoptosis, myofibroblast infiltration and TGF-β1 expression in the kidney of patients with glomerulonephritis (GN).Methods:Forty patients with various types of GN were included in the study. Myofibroblasts and TGF-β1 positive cells were detected in kidney biopsies by immunohistochemistry, while apoptotic cells were detected by the in situ end labelling of fragmented DNA. Results:Myofibroblasts were identified in the glomeruli of some patients with severe mesangioproliferative GN and glomerulosclerosis but a more intensive myofibroblast expression was found in the renal interstitium. TGF-β1 was expressed in the cytoplasm of tubular epithelial cells, in the renal interstitium and in the glomeruli of patients with GN. Apoptotic cells were mainly detected in the tubules and interstitium and were present in areas with intense myofibroblast infiltration. Positive correlations were observed between the intensity of myofibroblast expression in the interstitium and apoptosis in the tubulointerstitial area (r = 0.521, p < 0.01) as well as TGF-β1 expression (r = 0.462, p < 0.05) and degree of renal impairment (r = 0.430, p < 0.05). Conclusions:These observations suggest that myofibroblast infiltration and apoptosis along with TGF-β1 expression are associated with the development of interstitial fibrosis in patients with glomerular disease.

Background/Aims:The cellular and humoral factors involved in the development and progression of renal scarring have not been fully investigated. Transforming growth factor-β (TGF-β1) is considered to be the main fibrogenic growth factor and it is implicated in the pathogenesis of renal fibrosis in experimental and clinical nephropathies. On the other hand, collagen III is an important component of the extracellular matrix. In this study we attempted to identify any possible links between TGF-β1 and collagen III synthesis and expression with the expression of myofibroblasts in the evolution of renal scarring in human glomerular diseases. Methods:We studied retrospectively 40 patients with various types of primary and secondary glomerulonephritis (GN), with either proliferative or nonproliferative pattern, with emphasis on the renal synthesis of TGF-β1 and collagen III (detected by in situ hybridization) and their expression (detected by immunohistochemistry) as well as myofibroblast expression. The possible links of TGF-β1 expression with myofibroblast distribution (α-smooth muscle actin, α-SMA(+) cells) and with conventional histopathology and renal function was also examined. Results:TGF-β1 protein and mRNA were detected in the renal tubular epithelial cells and interstitium and to a lesser extent within glomeruli of patients with GN. Collagen III was mainly detected in the interstitium (peritubular and periglomerular areas) and to a lesser extent in the glomeruli. Messenger RNA for collagen III followed a similar peritubular and periglomerular distribution to that of TGF-β1 and α-SMA(+) interstitial cells. The intensity of interstitial TGF-β1 protein expression was significantly related to the degree of interstitial fibrosis (r = 0.628, p < 0.01), tubular atrophy (r = 0.612, p < 0.01), interstitial collagen III expression (r = 0.478, p < 0.05), and serum creatinine values (r = 0.722, p < 0.001). Also there was a close positive correlation between the severity of interstitial myofibroblast expression and interstitial TGF-β1 (r = 0.412, p < 0.05), as well as collagen III (r = 0.409, p < 0.05). In addition, a significant correlation was found between glomerular TGF-β1 expression and severity of glomerulosclerosis (r = 0.620, p < 0.01). Conclusion: The results of this study suggest that TGF-β1 plays an important role in the pathogenesis of fibrosis developing in human kidney, during the evolution of glomerular disease. Interstitial myofibroblasts may contribute to interstitial fibrosis through the synthesis and release of both TGF-β1 and collagen III.

Objective To investigate the reason for increasing norepinephrine (NE) levels reported in continuous ambulatory peritoneal dialysis (CAPD) patients.Methods Norepinephrine was measured in the plasma and peritoneal dialysate of CAPD patients (n= 22) and in the plasma and the urine of healthy subjects (n= 20). It was also measured in the plasma of patients with chronic renal failure (CRF) (n= 15) and patients on hemodialysis (HD) (n= 15).Results It was found that NE was increased in CAPD patients compared with healthy individuals (687 ± 221 pg/mL vs 199 ± 25 pg/mL, p< 0.01). The daily removal of NE from the peritoneum of CAPD patients was lower compared with the amount of NE excreted in the urine of healthy subjects. Plasma NE increased after infusion of peritoneal dialysate. In 15 new patients on CAPD, it was found that NE plasma levels increased from 329 ± 67 pg/mL before initiation of dialysis, to 584 ± 173 pg/mL after 12 months of treatment (p< 0.01). Finally, plasma NE in CAPD patients (687 ± 221 pg/mL) was significantly higher compared with the already increased levels in patients on HD or with CRF (406 ± 143 pg/mL and 378 ± 142 pg/mL, respectively).Conclusions It is concluded that CAPD in patients with end-stage renal disease is responsible for a progressive increase of plasma norepinephrine.

Summary Studies of the synthesis of integumental proteins during the feeding and non-feeding stages ofCeratitis capitata demonstrated stage specificity. The synthetic profile changed dramatically, showing a maximum of protein synthesis just before the larval wandering stage, followed by an abrupt decline. The comparison between synthetic and accumulation profiles indicated that some polypeptides must be internalized into the integument from the haemolymph. The major haemolymph proteins or arylphorins have already been documented to be incorporated into the integument. In the present work, we demonstrated the interalization of some haemocyte proteins into the integument. For that purpose, polyclonal antibodies were raised against total haemocyte proteins. Immunoblot analysis of haemocyte salt extractable proteins revealed that the protein bands at 36, 54, 58, 84, 110 and 130 kDa were immunoreactive with the total haemocyte antibodies. Cell-free protein synthesis, organ culture experiments and immunoblot analysis indicated that the 36-, 54- and 58-kDa polypeptides were synthesized only in the haemocytes and were probably internalized into the integument from the serum. The 36-kDa polypeptide was also demonstrated to be internalized into the fat body of white puparia. The immunofluorescence experiments suggested that the internalization of haemocyte proteins first occurs into the epidermal cells and then into the cuticle. The presence of haemocyte proteins in the integument was also demonstrated by immunofluorescence experiments in twoC. capitata mutants. These mutations affect the darkening and stiffening of the cuticle. The demonstration of 36-, 54- and 58-kDa haemocyte polypeptides in the integument reveals a hitherto unknown function of this cell type. Moreover, the demonstration of tyrosine binding to the 54- and 58-kDa polypeptides points to their potential involvement in the sclerotization process in the cuticle.

Cyclosporin-A (CsA) is often used in the treatment of nephrotic syndrome. The effectiveness of CsA and the value of C2 blood levels in the treatment of nephrotic syndrome, due to various glomerular diseases, were studied. Forty-two nephrotic patients (M/F 21/21), with well-preserved renal function (creatinine clearance 87± 20ml/min) were included in the study. The original diagnoses were minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), membranous nephropathy (MN), IgA nephropathy (IgAN), and lupus nephritis (LN). All patients were treated with prednisolone and CsA for 24 months. Cyclosporin-A C0 and C2 blood levels were determined at regular intervals. Remission of the nephrotic syndrome was observed in all patients with MCD, IgAN and LN, in 75 with FSGS and in 83with MN. Relapses were observed in some patients with MCD (25) and MN (36). The C0 levels were 93± 15 ng/ml and the corresponding C2 levels were 498± 110 ng/ml. However, significantly lower (340± 83 ng/ml) or higher (680± 127 ng/ml) to the average C2 levels were found in 6 patients (14). No relation of C0 and C2 levels with the remission and relapse rate of the nephrotic syndrome and with renal function impairment was observed. Small doses of CsA with prednisolone are effective in the treatment of nephrotic syndrome. Although an individual variation of C2 was observed for the same target C0 levels, no relation of C2 levels was found with the remission or relapse rate of the nephrotic syndrome.