Biopsy-proven BK virus nephropathy in renal transplant recipients: A -multi-central study from Turkey (BK-TURK STUDY).

AIM: BK polyomavirus infection is a challenging complication of renal transplantation. The management is not standardized and is based on reports from transplantation centers' experiences, usually with small sample sizes. Therefore, we aimed to present our countrywide experience with BK virus nephropathy (BKVN) in renal transplant recipients. MATERIALS AND METHODS: Our study was carried out with the participation of 30 transplantation centers from all regions of Turkey. Only cases with allograft biopsy-proven BKVN were included in the study. RESULTS: 13,857 patients from 30 transplantation centers were screened, and 207 BK nephropathy cases were included. The mean age was 46.4 ±  13.1 years, and 146 (70.5%) patients were male. The mean time to diagnosis of BK nephropathy was 15.8 ± 22.2 months after transplantation. At diagnosis, the mean creatinine level was 1.8 ±  0.7 mg/dL, and the mean estimated glomerular filtration rate was 45.8 ± 19.6 mL/min/1.73m2 . In addition to dose reduction or discontinuation of immunosuppressive drugs, 18 patients were treated with cidofovir, 11 patients with leflunomide, 17 patients with quinolones, 15 patients with intravenous immunoglobulin (IVIG), 5 patients with cidofovir plus IVIG, and 12 patients with leflunomide plus IVIG. None of the patients receiving leflunomide or leflunomide plus IVIG had allograft loss. During follow-up, allograft loss occurred in 32 (15%) out of 207 patients with BK nephropathy. CONCLUSION: BKVN is still a frequent cause of allograft loss in kidney transplantation and is not fully elucidated. The results of our study suggest that leflunomide treatment is associated with more favorable allograft outcomes.

Sclerostin and TNF-related weak inducer of apoptosis: can they be important in the patients with glomerulonephritis?

OBJECTIVE: Sclerostin is a protein produced by osteocytes, kidneys, and vascular cells and has many effects on kidney and vascular structures. Soluble TNF-related weak inducer of apoptosis is a proinflammatory cytokine that may cause glomerular and tubular injury and increase sclerostin expression. This study aimed to investigate serum sclerostin and soluble TNF-related weak inducer of apoptosis levels in patients with glomerulonephritis and the effects they may be associated with. METHODS: This cross-sectional study included 93 patients, 63 of whom were glomerulonephritis and 30 were healthy controls. Serum sclerostin, soluble TNF-related weak inducer of apoptosis, and 24-h urinary protein excretion were measured, and pulse wave velocity was calculated for arterial stiffness. RESULTS: Serum sclerostin and soluble TNF-related weak inducer of apoptosis were higher in glomerulonephritis patients than in the control group, and serum sclerostin and soluble TNF-related weak inducer of apoptosis levels were correlated with both proteinuria and pulse wave velocity. In addition, in the regression analysis, serum sclerostin and soluble TNF-related weak inducer of apoptosis levels were found to be independent predictors of proteinuria in patients with glomerulonephritis. CONCLUSION: This is the first study to show that serum sclerostin and soluble TNF-related weak inducer of apoptosis are elevated in glomerulonephritis patients, and these two markers correlate with arterial stiffness and proteinuria in these patients. Considering the effects of sclerostin and soluble TNF-related weak inducer of apoptosis in patients with glomerulonephritis, we think these mechanisms will be the target of both diagnosis and new therapies.

An update on diagnosis and treatment of ANCA associated renal vasculitis.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides are a group of diseases characterised by necrotizing inflammation of small vessels such as arterioles, venules, and capillaries. ANCA-associated vasculitides (AAV) are referred to as small vessel vasculitides. Three AAV subgroups, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic GPA (EGPA), are defined according to clinical features. The most common disease with renal involvement in AAV is MPA Approximately 90% of patients with MPA have renal involvement. While this rate is 70-80% in GPA, less than half of EGPA patients have renal involvement. Untreated survival in AAVs is less than one year. With appropriate immunosuppressive therapy, the 5-year renal survival rate is 70-75%. Without therapy, the prognosis is poor but treatments, typically immunosuppressants, have improved survival, albeit with considerable morbidity from glucocorticoids and other immunosuppressive medications. Current challenges include improving the measures of disease activity and risk of relapse, uncertainty about optimal therapy duration and a need for targeted therapies with fewer adverse effects. In this review, we described the treatment of renal involvement in AAV in line with current studies.

Can eculizumab be an option in traditional treatment-resistant ulcerative colitis?

Atypical/complement-mediated hemolytic uremic syndrome (A-HUS/CM-HUS) is a hereditary or sporadic disease with thrombotic microangiopathy (TMA). Diarrhea is a trigger that can cause attacks of CM-HUS. Although there are opinions that complement system activation plays a role in intestinal inflammation in patients with inflammatory bowel disease, the association of TMA with inflammatory bowel disease (IBD) has rarely been reported. In our case, a CM-HUS case that developed without an additional triggering factor in the course of ulcerative colitis (UC) was successfully treated with eculizumab, and then UC remission was also achieved. In this context, we would like to point out that the irregularities in the alternative pathway of the complement system may cause clinical findings in extra-renal organs, and the complement system may also play a role in the pathogenesis of inflammatory bowel disease. In addition, we think that our case may guide further studies on the usability of anti-complement therapies in treating patients with IBD who are resistant to conventional treatments.

Sclerostin and TNF-related weak inducer of apoptosis: can they be important in the patients with glomerulonephritis?

SUMMARY OBJECTIVE: Sclerostin is a protein produced by osteocytes, kidneys, and vascular cells and has many effects on kidney and vascular structures. Soluble TNF-related weak inducer of apoptosis is a proinflammatory cytokine that may cause glomerular and tubular injury and increase sclerostin expression. This study aimed to investigate serum sclerostin and soluble TNF-related weak inducer of apoptosis levels in patients with glomerulonephritis and the effects they may be associated with. METHODS: This cross-sectional study included 93 patients, 63 of whom were glomerulonephritis and 30 were healthy controls. Serum sclerostin, soluble TNF-related weak inducer of apoptosis, and 24-h urinary protein excretion were measured, and pulse wave velocity was calculated for arterial stiffness. RESULTS: Serum sclerostin and soluble TNF-related weak inducer of apoptosis were higher in glomerulonephritis patients than in the control group, and serum sclerostin and soluble TNF-related weak inducer of apoptosis levels were correlated with both proteinuria and pulse wave velocity. In addition, in the regression analysis, serum sclerostin and soluble TNF-related weak inducer of apoptosis levels were found to be independent predictors of proteinuria in patients with glomerulonephritis. CONCLUSION: This is the first study to show that serum sclerostin and soluble TNF-related weak inducer of apoptosis are elevated in glomerulonephritis patients, and these two markers correlate with arterial stiffness and proteinuria in these patients. Considering the effects of sclerostin and soluble TNF-related weak inducer of apoptosis in patients with glomerulonephritis, we think these mechanisms will be the target of both diagnosis and new therapies.

Capillaroscopic appearance of nailfold vasculature of diabetic nephropathy patients

ABSTRACT Objectives: Diabetic nephropathy is a microvascular complication of diabetes and the most common cause of end-stage renal failure throughout the world. Videocapillaroscopy is a simple and noninvasive method that can display capillaries in the nail bed at the micron level. A few studies have been conducted on detecting retinopathy, another important diabetic microvascular complication, with videocapillaroscopy; however, no comprehensive study has been performed on diabetic nephropathy. We aimed to determine the relationship between nephropathy and capillaroscopic changes. Subjects and methods: Capillaroscopic findings of 144 patients with type 2 diabetes and 88 healthy controls were assessed prospectively by nailfold videocapillaroscopy. Twelve capillaroscopic findings were evaluated in all subjects. Results: Patients with albuminuria had more capillary aneurysms (15.5%), more microhemorrhages (15.5%), greater tortuosity (76.3%), more neoformations (29.9%), more bizarre capillaries (49.5%) and more bushy capillaries (20.6%) than the control group. In logistic regression analysis, tortuosity was significantly correlated with albuminuria (OR: 2.451, p = 0.048). Conclusions: Our findings show that the application of nailfold videocapillaroscopy can detect microvascular abnormalities in the nail bed that occur in diabetes mellitus patients compared to healthy people. Although there was no difference in the microvascular changes among the stages of diabetic nephropathy, a relationship between tortuosity and albuminuria was identified by logistic regression analysis. Nailfold videocapillaroscopy may be a new application that can be used to screen the microvascular changes that occur in diabetes mellitus.

Middle-term outcomes in renal transplant recipients with COVID-19: a national, multicenter, controlled study.

Background: In this study, we evaluated 3-month clinical outcomes of kidney transplant recipients (KTR) recovering from COVID-19 and compared them with a control group. Method: The primary endpoint was death in the third month. Secondary endpoints were ongoing respiratory symptoms, need for home oxygen therapy, rehospitalization for any reason, lower respiratory tract infection, urinary tract infection, biopsy-proven acute rejection, venous/arterial thromboembolic event, cytomegalovirus (CMV) infection/disease and BK viruria/viremia at 3 months. Results: A total of 944 KTR from 29 different centers were included in this study (523 patients in the COVID-19 group; 421 patients in the control group). The mean age was 46 ± 12 years (interquartile range 37-55) and 532 (56.4%) of them were male. Total number of deaths was 8 [7 (1.3%) in COVID-19 group, 1 (0.2%) in control group; P = 0.082]. The proportion of patients with ongoing respiratory symptoms [43 (8.2%) versus 4 (1.0%); P < 0.001] was statistically significantly higher in the COVID-19 group compared with the control group. There was no significant difference between the two groups in terms of other secondary endpoints. Conclusion: The prevalence of ongoing respiratory symptoms increased in the first 3 months post-COVID in KTRs who have recovered from COVID-19, but mortality was not significantly different.

Early postoperative changes of sphingomyelins and ceramides after laparoscopic sleeve gastrectomy.

BACKGROUND: This study aimed to determine early postoperative changes of serum sphingomyelin (SM) and ceramide (CER) species following laparoscopic sleeve gastrectomy (LSG). METHODS: Twenty obese patients [mean body mass index (BMI) 45,64 ± 6,10 kg/m2] underwent LSG and normal weight control patients (mean BMI 31,51 ± 6,21 kg/m2) underwent laparoscopic cholecystectomy. Fasting blood samples were collected prior to surgery, at day 1 and day 30 after surgery. Circulating levels of C16-C24 SMs, C16-C24 CERs and sphingosine-1-phosphate (S1P) were determined by an optimized multiple reaction monitoring (MRM) method using ultra fast-liquid chromatography (UFLC) coupled with tandem mass spectrometry (MS/MS). Serum activity of neutral sphingomyelinase (N-SMase) was assayed by standard kit methods, and ceramide-1-phosphate (C1P) levels were determined by enzyme-linked immunosorbent assay (ELISA). Lipid profile, routine biochemical and hormone parameters were assayed by standard kit methods. Insulin sensitivity was evaluated using homeostatic model assessment for insulin resistance (HOMA IR). RESULTS: A significant decrease was observed in serum levels of very-long-chain C24 SM, very-long-chain C22-C24 CERs, HOMA-IR, N-SMase and C1P in LSG patients after postoperation day 1 and day 30 compared to preoperation levels. At 30 days postsurgery, BMI was reduced by 11%, fasting triglycerides were significantly decreased, and insulin sensitivity was increased compared to presurgery values. A significant positive correlation was found between HOMA-IR and serum levels of C22-C24 CERs in LSG patients. CONCLUSION: We conclude that very long chain CERs may mediate improved insulin sensitivity after LSG.

Antimicrobial activities of essential oil and hexane extract of Florence fennel [Foeniculum vulgare var. azoricum (Mill.) Thell.] against foodborne microorganisms.

The objective of this study was to determine the chemical compositions of the essential oil and hexane extract isolated from the inflorescence, leaf stems, and aerial parts of Florence fennel and the antimicrobial activities of the essential oil, hexane extract, and their major component, anethole, against a large variety of foodborne microorganisms. Gas chromatography and gas chromatography-mass spectrometry analysis showed that the essential oils obtained from inflorescence, leaf stems, and whole aerial parts contained (E)-anethole (59.28-71.69%), limonene (8.30-10.73%), apiole (trace to 9.23%), beta-fenchyl acetate (3.02-4.80%), and perillene (2.16-3.29%) as the main components. Likewise, the hexane extract of the plant sample exhibited a similar chemical composition, and it contained (E)-anethole (53.00%), limonene (27.16%), gamma-terpinene (4.09%), and perillene (3.78%). However, the hexane extract also contained less volatile components such as n-hexadecanoic acid (1.62%), methyl palmitate (1.17%), and linoleic acid (1.15%). The in vitro antimicrobial assays showed that the essential oil, anethole, and hexane extract were effective against most of the foodborne pathogenic, saprophytic, probiotic, and mycotoxigenic microorganisms tested. The results of the present study revealed that (E)-anethole, the main component of Florence fennel essential oil, is responsible for the antimicrobial activity and that the essential oils as well as the hexane extract can be used as a food preservative. This study is the first report showing the antimicrobial activities of essential oil and hexane extract of Florence fennel against probiotic bacteria.

Chemical composition of hydrodistilled essential oil of Artemisia incana (L.) Druce and antimicrobial activity against foodborne microorganisms.

The oil obtained by hydrodistillation from the aerial parts of Artemisia incana (L.) Druce from Turkey was analyzed by GC and GC/MS. Sixty-three compounds were characterized, representing 97.2% of the total components detected, and camphor (19.0%), borneol (18.9%), 1,8-cineole (14.5%), bornyl acetate (7.8%), camphene (4.9%), and alpha-thujone (4.8%) were identified as predominant components. The essential oil was also tested for its antimicrobial activity against 44 different foodborne microorganisms, including 26 bacteria, 15 fungi, and 3 yeast species. The essential oil of A. incana exhibited considerable inhibitory effects against all bacteria, fungi, and yeast species tested. However, the oil showed lower inhibitory activity against the tested bacteria than the reference antibiotics.

Antioxidant properties and total phenolic content of eight Salvia species from Turkey.

Methanolic extracts of eight Salvia species, namely S. aethiopis, S. candidissima, S. limbata, S. microstegia, S. nemorosa, S. pachystachys, S. verticillata, and S. virgata, sampled from Eastern Anatolia in Turkey, were screened for their possible antioxidant activities by two complementary test systems, namely DPPH free radical scavenging and beta-carotene/linoleic acid. Total phenolic content of the extracts of Salvia species were performed Folin-Ciocalteu reagent and gallic acid used as standard. A wide variation has been observed among species in terms of antioxidant activity and total phenolic content. In both DPPH and beta-carotene system, the most active plant was Salvia verticillata with a value of IC50=18.3 microg/ml and 75.8%, respectively. This species also has the highest total phenolic content (167.1 mgGAE/g DW). The total amount of phenolics was between 50.3 to 167.1 mgGAE/g DW among species. A positive linear correlation was observed between total phenolic content and antioxidant activity of the extracts. The results suggest that the extract of Salvia species, notably Salvia verticillata with the highest antioxidant activity, can be used as natural antioxidants in the food industry.

Antimicrobial and antioxidant activity of the essential oil and methanol extract of Nepeta cataria.

Catnip (Nepeta cataria) is an important medicinal herb belonging to the mint family, Lamiaceae. In this study, the in vitro antimicrobial and antioxidant activities of the essential oil and methanol extract from Nepeta cataria, and its essential oil composition were investigated. The essential oil, which has 4aalpha,7alpha,7abeta-nepetalactone (70.4%), 4aalpha,7alpha,7abeta-nepetalactone (6.0%), thymol (2.3%), and 4aalpha,7alpha, 7abeta3-nepetalactone (2.5%), as main components, exhibited activity against eleven bacteria, and twelve fungi and a yeast, C. albicans; with Minimum Inhibitory Concentrations (MIC) values ranging from 12.50 to 250 microl/ml; the methanol extract showed weaker activity. The samples were also subjected to a screening for their possible antioxidant activities by using 2.2-diphenyl-1-picrylhydrazyl (DPPH) and beta-carotene/linoleic acid assays. In DPPH assay, the extract showed slight antioxidant activity whereas the essential oil remained inactive. In the latter case, both the extract and the essential oil exerted weak activity having inhibiton ratios of linoleic acid oxidation at 16.4% and 27.0%, respectively. The weak antioxidative nature of the extract could be attributed to the low phenolic content, estimated as gallic acid equivalent at 22.6 +/- 2.07 microg/ml or 2.26%. In both systems, antioxidant capacity of BHT was determined in parallel experiments.

Antioxidant Properties and Total Phenolic Content of Eight Salvia Species from Turkey

Methanolic extracts of eight Salvia species, namely S. aethiopis, S. candidissima, S. limbata, S. microstegia, S. nemorosa, S. pachystachys, S. verticillata, and S. virgata, sampled from Eastern Anatolia in Turkey, were screened for their possible antioxidant activities by two complementary test systems, namely DPPH free radical scavenging and b-carotene/linoleic acid. Total phenolic content of the extracts of Salvia species were performed Folin-Ciocalteu reagent and gallic acid used as standard. A wide variation has been observed among species in terms of antioxidant activity and total phenolic content. In both DPPH and b-carotene system, the most active plant was Salvia verticillata with a value of IC50=18.3 μg/ml and 75.8 percent, respectively. This specie also has the highest total phenolic content (167.1 mgGAE/g DW). The total amount of phenolics was between 50.3 to 167.1 mg GAE/g DW among species. A positive linear correlation was observed between total phenolic content and antioxidant activity of the extracts. The results suggest that the extract of Salvia species, notably Salvia verticillata with the highest antioxidant activity, can be used as natural antioxidants in the food industry.

Antifungal, phytotoxic and insecticidal properties of essential oil isolated from Turkish Origanum acutidens and its three components, carvacrol, thymol and p-cymene.

The chemical composition of essential oil isolated by hydrodistillation from the aerial parts of Origanum acutidens was analyzed by GC-MS. Carvacrol (87.0%), p-cymene (2.0%), linalool acetate (1.7%), borneol (1.6%) and beta-caryophyllene (1.3%) were found to be as main constituents. Antifungal, phytotoxic and insecticidal activities of the oil and its aromatic monoterpene constituents, carvacrol, p-cymene and thymol were also determined. The antifungal assays showed that O. acutidens oil, carvacrol and thymol completely inhibited mycelial growth of 17 phytopathogenic fungi and their antifungal effects were higher than commercial fungicide, benomyl. However, p-cymene possessed lower antifungal activity. The oil, carvacrol and thymol completely inhibited the seed germination and seedling growth of Amaranthus retroflexus, Chenopodium album and Rumex crispus and also showed a potent phytotoxic effect against these plants. However, p-cymene did not show any phytotoxic effect. Furthermore, O. acutidens oil showed 68.3% and 36.7% mortality against Sitophilus granarius and Tribolium confusum adults, respectively. The findings of the present study suggest that antifungal and herbicidal properties of the oil can be attributed to its major component, carvacrol, and these agents have a potential to be used as fungicide, herbicide as well as insecticide.

Chemical composition and antimicrobial and antioxidant activities of the essential oil and methanol extract of Hippomarathrum microcarpum (Bieb.) from Turkey.

Hippomarathrum microcarpum grows wild in eastern Anatolia, Turkey, and is a plant utilized as food by people. In this study, the in vitro antimicrobial and antioxidant activities of the essential oil and methanol extract from H. microcarpum and its essential oil composition were investigated. The essential oil, which has bornyl acetate, caryophyllene oxide, and beta-caryophyllene as its main components, exhibited activity against eight bacteria, nine fungi, and a yeast, Candida albicans, with minimum inhibitory concentration values ranging from 62.50 to 125 muL/mL; the methanol extract showed weak activity. The antioxidant activity of these extracts was assessed by the beta-carotene bleaching test and the 1,1'-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging test. The inhibition of linoleic acid oxidation was very weak for both extracts tested. The inhibition percentages were found to be 22.9 and 33.5% for methanol and essential oil, respectively, at the concentration of 2 g/L. The oil scavenged DPPH at higher concentrations (IC50 = 10.69 +/- 0.05 mg/mL), but the methanol extract exhibited no activity. The total phenolic content of the methanol extract was found to be 4.7 +/- 0.1%.

Nigella sativa (black seed) oil does not affect the T-helper 1 and T-helper 2 type cytokine production from splenic mononuclear cells in allergen sensitized mice.

Nigella sativa Linn. (Ranunculaceae) is known to have beneficial effects on a wide range of diseases including asthma. However, the mechanism of action in asthma and other allergic diseases is not entirely clear. The present study was planned to evaluate the effects of Nigella sativa on cytokine production of splenic mononuclear cells in ova-sensitized mice. Nineteen two-month-old BALB/c mice were given 0.3 mL of Nigella sativa oil by oro-eosophageal cannula once a day for a month. The control group consisting of 10 mice took 0.3 mL of 0.9% saline solution by the same route for the same period. In the third week of the study, all mice were sensitized by means of intraperitoneal injections of 20 microg of ovalbumin (OVA-Grade VI, Sigma). Ova injections were repeated three times with 7-day intervals. After another week, all mice were sacrificed by means of cervical dislocation. Then the splenic mononuclear cells (MNCs) of mice were cultured with OVA or Concavalin A (Con-A). From the culture supernatants, IL-4, IL-10 and IFN-gamma were assessed by means of ELISA. The cytokine production of splenic MNCs of mice that were given Nigella sativa for 30 days was not significantly different than those who took saline solution instead. In conclusion, Nigella sativa oil seems not to have an immunomodulatory effect on Th1 and Th2 cell responsiveness to allergen stimulation.