Fabry Disease Prevalence in Renal Replacement Therapy in Turkey

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder resulting from lack of alpha-galactosidase A (AGALA) activity in lysosomes. Objective: In this multicenter study, we aimed to evaluate the prevalence of FD in renal transplant (Tx) recipients in Turkey. We also screened dialysis patients as a control group. Methods: All Tx and dialysis patients were screened regardless of the presence of a primary disease. We measured the AGALA activity in all male patients as initial analysis. Mutation analysis was performed in male patients with decreased AGALA activity and in female patients as the initial diagnostic assay. Results: We screened 5,657 patients. A total of 17 mutations were identified. No significant difference was observed between the groups regarding the prevalence of patients with mutation. We found FD even in patients with presumed primary kidney diseases. Seventy-one relatives were analyzed and mutation was detected in 43 of them. We detected a patient with a new, unknown mutation (p.Cys223) in the GLA gene. Conclusions: There are important implications of the screening. First, detection of the undiagnosed patients leads to starting appropriate therapies for these patients. Second, the transmission of the disease to future generations may be prevented by prenatal screening after appropriate genetic counseling. In conclusion, we suggest screening of kidney Tx candidates for FD, regardless of etiologies of chronic kidney disease. (C) 2019 S. Karger AG, BaselC1 [Yalin, Serkan Feyyaz; Senates, Banu Erkalma; Oruc, Meric; Altiparmak, Mehmet Riza; Seyahi, Nurhan] Istanbul Univ Cerrahpasa, Cerrahpasa Med Fac, Dept Nephrol, Istanbul, Turkey.[Eren, Necmi] Kocaeli Univ, Dept Nephrol, Med Fac, Kocaeli, Turkey.[Sinangil, Ayse; Ecder, Tevfik] Bilim Univ, Dept Nephrol, Med Fac Med, Istanbul, Turkey.[Yilmaz, Vural Taner; Kocak, Huseyin] Akdeniz Univ, Div Nephrol, Med Fac, Antalya, Turkey.[Tatar, Erhan; Uslu, Adam] Bozyaka Training & Res Hosp, Dept Nephrol, Izmir, Turkey.[Ucarf, Ali Riza; Demir, Erol; Caliskan, Yasar; Turkmen, Aydin] Istanbul Univ, Fac Med, Div Nephrol, Istanbul, Turkey.[Sevinc, Mustafa; Basturk, Taner] Sisli Hamidiye Etfal Training & Res Hosp, Dept Nephrol, Istanbul, Turkey.[Can, Ozgur; Ogutmen, Melike Betul] Haydarpasa Training & Res Hosp, Dept Nephrol, Istanbul, Turkey.[Gurkan, Alp; Kinalp, Can] Medicana, Dept Nephrol, Istanbul, Turkey.[Arik, Nurol] Ondokuz Mayis Univ, Dept Nephrol, Med Fac, Samsun, Turkey.[Ecder, Sabahat Alisir] Medeniyet Univ, Div Nephrol, Goztepe Training & Res Hosp, Istanbul, Turkey.[Uyar, Murathan] Gaziosmanpasa Hosp, Dept Nephrol, Istanbul, Turkey.[Yasar, Murat; Dursun, Belda] Pamukkale Univ, Dept Nephrol, Med Fac, Denizli, Turkey.[Gulcicek, Sibel] Istanbul Training & Res Hosp, Dept Nephrol, Istanbul, Turkey.[Mese, Meral; Bahcebasi, Zerrin Bicik] Dr Lufti Kirdar Kartal Training & Res Hosp, Dept Nephrol, Istanbul, Turkey.[Dheir, Hamad; Sipahi, Savas; Genc, Ahmed] Sakarya Univ, Dept Nephrol, Tip Med Fac, Sakarya, Turkey.[Cakir, Ulkem] Acibadem Univ, Dept Nephrol, Med Fac, Istanbul, Turkey.[Cevher, Simal Koksal; Dede, Fatih] Ankara Numune Training & Res Hosp, Dept Nephrol, Ankara, Turkey.[Turkmen, Kultigin] Necmettin Erbakan Univ, Div Nephrol, Meram Med Fac, Konya, Turkey.[Guven, Bahtisen] Bahcesehir Univ, Dept Nephrol, Med Fac, Istanbul, Turkey.[Taymez, Dilek Guven] Kocaeli State Hosp, Dept Nephrol, Kocaeli, Turkey.[Yelken, Berna] Mem Hosp, Dept Nephrol, Istanbul, Turkey

Hirsutella sinensis mycelium suppresses interleukin-1β and interleukin-18 secretion by inhibiting both canonical and non-canonical inflammasomes

Cordyceps sinensis is a medicinal mushroom used for centuries in Asian countries as a health supplement and tonic. Hirsutella sinensis—the anamorphic, mycelial form of C. sinensis—possesses similar properties, and is increasingly used as a health supplement. Recently, C. sinensis extracts were shown to inhibit the production of the pro-inflammatory cytokine IL-1β in lipopolysaccharide-treated macrophages. However, the molecular mechanism underlying this process has remained unclear. In addition, whether H. sinensis mycelium (HSM) extracts also inhibit the production of IL-1β has not been investigated. In the present study, the HSM extract suppresses IL-1β and IL-18 secretion, and ATP-induced activation of caspase-1. Notably, we observed that HSM not only reduced expression of the inflammasome component NLRP1 and the P2X(7)R but also reduced the activation of caspase-4, and ATP-induced ROS production. These findings reveal that the HSM extract has anti-inflammatory properties attributed to its ability to inhibit both canonical and non-canonical inflammasomes

Intelligence, educational attainment, and brain structure in those at familial high‐risk for schizophrenia or bipolar disorder

First‐degree relatives of patients diagnosed with schizophrenia (SZ‐FDRs) show similar patterns of brain abnormalities and cognitive alterations to patients, albeit with smaller effect sizes. First‐degree relatives of patients diagnosed with bipolar disorder (BD‐FDRs) show divergent patterns; on average, intracranial volume is larger compared to controls, and findings on cognitive alterations in BD‐FDRs are inconsistent. Here, we performed a meta‐analysis of global and regional brain measures (cortical and subcortical), current IQ, and educational attainment in 5,795 individuals (1,103 SZ‐FDRs, 867 BD‐FDRs, 2,190 controls, 942 schizophrenia patients, 693 bipolar patients) from 36 schizophrenia and/or bipolar disorder family cohorts, with standardized methods. Compared to controls, SZ‐FDRs showed a pattern of widespread thinner cortex, while BD‐FDRs had widespread larger cortical surface area. IQ was lower in SZ‐FDRs (d = −0.42, p = 3 × 10−5), with weak evidence of IQ reductions among BD‐FDRs (d = −0.23, p = .045). Both relative groups had similar educational attainment compared to controls. When adjusting for IQ or educational attainment, the group‐effects on brain measures changed, albeit modestly. Changes were in the expected direction, with less pronounced brain abnormalities in SZ‐FDRs and more pronounced effects in BD‐FDRs. To conclude, SZ‐FDRs and BD‐FDRs show a differential pattern of structural brain abnormalities. In contrast, both had lower IQ scores and similar school achievements compared to controls. Given that brain differences between SZ‐FDRs and BD‐FDRs remain after adjusting for IQ or educational attainment, we suggest that differential brain developmental processes underlying predisposition for schizophrenia or bipolar disorder are likely independent of general cognitive impairment