Sample records for balkan endemic nephropathy
-
The continuing medical mystery of Balkan Endemic Nephropathy
Crosby, Lynn M.; Tatu, Calin A.; Orem, William H.; Pavlovic MD PhD, Nikola
2015-01-01
Balkan Endemic Nephropathy (BEN) is a disease of subtle onset and insidious progression that typically occurs between the 4th and 6th decade in long‐resident individuals in highly specific geographic locations of the Balkan region and affects 1 – 5% of the population. Though it does not follow typical Mendelian genetics, there is a familial pattern of occurrence. Although residents may live only a few kilometers apart, certain locations are highly affected while others close by, even as close as across the road, remain unscathed. Because of this geographic selectivity scientists have searched for an environmental cause. It is thought that exposure to the toxic plant Aristolochia clematitis is to blame. Genotoxic N‐heterocyclic or polycyclic aromatic containing coal water leachates entering cultivated soil and drinking water are also a possible cause due to the proximity and predictive power of endemic foci to coal deposits. Evidence for Ochratoxin A fungal poisoning also exists. High levels of phthalates have been measured in BEN‐endemic drinking water. BEN is a probably a multifactorial disease that may result from exposure through some of above‐mentioned environmental sources, with genetic factors contributing. This review will discuss recent research concerning the etiology, potential therapies for the treatment of nephropathy, and unexplored research directions for this chronic kidney disease.
-
The etiology of Balkan endemic nephropathy: Still more questions than answers
Tatu, C.A.; Orem, W.H.; Finkelman, R.B.; Feder, G.L.
1998-01-01
Balkan endemic nephropathy (BEN) has attracted increasing attention as a possible environmental disease, and a significant amount of research from complementary scientific fields has been dedicated to its etiology. There are two actual competing theories attempting to explain the cause of this kidney disease: 1) the mycotoxin hypothesis, which considers that BEN is produced by ochratoxin A ingested intermittently in small amounts by the individuals in the endemic regions, and 2) the Pliocene lignite hypothesis, which proposes that the disease is caused by long-term exposure to polycyclic aromatic hydrocarbons and other toxic organic compounds leaching into the well drinking water from low rank coals underlying or proximal to the endemic settlements. We outline the current developments and future prospects in the study of BEN and differentiate possible factors and cofactors in disease etiology.
-
Relationship between weathered coal deposits and the etiology of Balkan endemic nephropathy
Feder, G.L.; Radovanovic, Z.; Finkelman, R.B.
1991-01-01
Field studies in epidemiology and environmental geochemistry in areas in Yugoslavia containing villages with a high incidence of Balkan endemic nephropathy (BEN), indicate a possible relationship between the presence of low-rank coal deposits and the etiology of BEN. Preliminary results from qualitative chemical analyses of drinking water from shallow farm wells indicate the presence of soluble polar aromatic and polynuclear aromatic hydrocarbons. These compounds may be derived from weathering of low-rank coals occurring in the vicinity of the endemic villages. All of the endemic villages are in alluvial valleys of tributaries to the Danube River. All except one of the clusters of endemic villages are located in the vicinity of known Pliocene age coals. Detailed sampling of the drinking waters and the nearby coals are being undertaken to identify a possible etiologic factor.
-
The etiology of Balkan endemic nephropathy: still more questions than answers.
Tatu, C A; Orem, W H; Finkelman, R B; Feder, G L
1998-01-01
Balkan endemic nephropathy (BEN) has attracted increasing attention as a possible environmental disease, and a significant amount of research from complementary scientific fields has been dedicated to its etiology. There are two actual competing theories attempting to explain the cause of this kidney disease: 1) the mycotoxin hypothesis, which considers that BEN is produced by ochratoxin A ingested intermittently in small amounts by the individuals in the endemic regions, and 2) the Pliocene lignite hypothesis, which proposes that the disease is caused by long-term exposure to polycyclic aromatic hydrocarbons and other toxic organic compounds leaching into the well drinking water from low rank coals underlying or proximal to the endemic settlements. We outline the current developments and future prospects in the study of BEN and differentiate possible factors and cofactors in disease etiology. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:9799184
-
How common is Balkan endemic nephropathy among immigrants in endemic regions?
Đukanović, Ljubica; Račić, Maja; Marić, Ivko; Maksimović, Zlatko; Simić, Jelena; Aleksić, Jela; Stanković, Sanja; Pejović, Vesna; Ležaić, Višnja
2018-05-19
In the early 1970s, a number of authors described the development of Balkan endemic nephropathy (BEN) in immigrants in endemic regions. The aim of this study was to examine whether immigrants in endemic regions are suffering from BEN today. The study involved 193 residents of two endemic regions divided into three groups: two groups of native residents-(1) members of BEN families, (2) members of non-BEN families, and (3) immigrants, who had moved from non-affected settlements to the endemic regions of Kolubara (38 years ago) or Semberia (20 years ago). All persons were subjected to an interview, objective examination, kidney ultrasound, and laboratory analysis to detect the presence of BEN consensus diagnostic criteria. The number of immigrants with BEN biomarkers outside cutoff values was significantly lower than for BEN family members. Five BEN family members met diagnostic criteria for BEN and four for suspected BEN. Although five non-BEN family members had different combinations of BEN biomarkers, all of them had diseases other than BEN in which these biomarkers also occurred. None of the immigrants met the criteria for BEN. Nevertheless, one descendant of an immigrant, a 78-year-old male, whose mother was from a non-BEN family in the Kolubara district, exhibited all the criteria for BEN: alpha1-microglobulinuria, chronic renal failure, and anemia. While 30 years ago, BEN was reported equally among immigrants and natives, currently it is diagnosed in some BEN family members in the eighth decade of life, but extremely rarely in immigrants also in old age.
-
Niagolova, Nedialka; McElmurry, Shawn P; Voice, Thomas C; Long, David T; Petropoulos, Evangelos A; Havezov, Ivan; Chou, Karen; Ganev, Varban
2005-03-01
This study explored two hypotheses relating elevated concentrations of nitrogen species in drinking water and the disease Balkan Endemic Nephropathy (BEN). Drinking water samples were collected from a variety of water supplies in both endemic and non-endemic villages in the Vratza and Montana districts of Bulgaria. The majority of well water samples exceeded US drinking water standards for nitrate + nitrite. No statistically significant difference was observed for any of the nitrogen species between villages classified as endemic and non-endemic. Other constituents (sodium, potassium and chloride) known to be indicators of anthropogenic pollution were also found at elevated concentrations and all followed the order wells > springs > taps. This ordering coincides with the proximity of human influences to the water sources. Our results clearly establish an exposure pathway between anthropogenic activity and drinking water supplies, suggesting that the causative agent for BEN could result from surface contamination.
-
Jelaković, Bojan; Nikolić, Jovan; Radovanović, Zoran; Nortier, Joelle; Cosyns, Jean-Pierre; Grollman, Arthur P.; Bašić-Jukić, Nikolina; Belicza, Mladen; Bukvić, Danica; Čavaljuga, Semra; Čvorišćec, Dubravka; Cvitković, Ante; Dika, Živka; Dimitrov, Plamen; Đukanović, Ljubica; Edwards, Karen; Ferluga, Dušan; Fuštar-Preradović, Ljubica; Gluhovschi, Gheorghe; Imamović, Goran; Jakovina, Tratinčica; Kes, Petar; Leko, Ninoslav; Medverec, Zvonimir; Mesić, Enisa; Miletić-Medved, Marica; Miller, Frederick; Pavlović, Nikola; Pasini, Josip; Pleština, Stjepko; Polenaković, Momir; Stefanović, Vladislav; Tomić, Karla; Trnačević, Senaid; Vuković Lela, Ivana; Štern-Padovan, Ranka
2014-01-01
Currently used diagnostic criteria in different endemic (Balkan) nephropathy (EN) centers involve different combinations of parameters, various cut-off values and many of them are not in agreement with proposed international guidelines. Leaders of EN centers began to address these problems at scientific meetings, and this paper is the outgrowth of those discussions. The main aim is to provide recommendations for clinical work on current knowledge and expertise. This document is developed for use by general physicians, nephrologists, urologist, public health experts and epidemiologist, and it is hoped that it will be adopted by responsible institutions in countries harboring EN. National medical providers should cover costs of screening and diagnostic procedures and treatment of EN patients with or without upper urothelial cancers. PMID:24166461
-
Health effects of toxic organic compounds from coal; the case Balkan endemic nephropathy (BEN)
Orem, W.H.; Tatu, C.A.
2001-01-01
Balkan endemic nephropathy (BEN) is a serious kidney disease that occurs only in clusters of rural villages located in tributary valleys of the Danube River in the Balkan Peninsula. It is believed that at least 25,000 persons are suffering from BEN or are suspected of having the disease and that the total number of people at risk may exceed 100,000. BEN was first described as a distinct medical entity in 1956, but it may have existed undescribed for many centuries. The geographic distribution of the disease has not changed significantly since the 1950's. Villages afflicted in the past continue to have cases of BEN, while villages with no history of BEN (some of which are only a few miles from affected villages) have remained free of this disease. Work by the U.S. Geological Survey and others in the early 1990's noted the close correspondence between the location of the affected villages and the occurrence of coal deposits, specifically lignites deposited in the Pliocene Epoch 5.3 million to 1.6 million years ago.
-
Endemic Nephropathy Around the World.
Gifford, Fiona J; Gifford, Robert M; Eddleston, Michael; Dhaun, Neeraj
2017-03-01
There have been several global epidemics of chronic kidney disease of unknown etiology (CKD u ). Some, such as Itai-Itai disease in Japan and Balkan endemic nephropathy, have been explained, whereas the etiology of others remains unclear. In countries such as Sri Lanka, El Salvador, Nicaragua, and India, CKD u is a major public health problem and causes significant morbidity and mortality. Despite their geographical separation, however, there are striking similarities between these endemic nephropathies. Young male agricultural workers who perform strenuous labor in extreme conditions are the worst affected. Patients remain asymptomatic until end-stage renal failure. Biomarkers of tubular injury are raised, and kidney biopsy shows chronic interstitial nephritis with associated tubular atrophy. In many of these places access to dialysis and transplantation is limited, leaving few treatment options. In this review we briefly describe the major historic endemic nephropathies. We then summarize the epidemiology, clinical features, histology and clinical course of CKD u in Mesoamerica, Sri Lanka, India, Egypt, and Tunisia. We draw comparisons between the proposed etiologies and supporting research. Recognition of the similarities may reinforce the international drive to establish causality and to effect prevention.
-
Organic compounds in water extracts of coal: links to Balkan endemic nephropathy.
Maharaj, S V M; Orem, W H; Tatu, C A; Lerch, H E; Szilagyi, D N
2014-02-01
The Pliocene lignite hypothesis is an environmental hypothesis that has been proposed to explain the etiology of Balkan endemic nephropathy (BEN). Aqueous leaching experiments were conducted on a variety of coal samples in order to simulate groundwater leaching of organic compounds, and to further test the role of the Pliocene lignite hypothesis in the etiology of BEN. Experiments were performed on lignite coal samples from endemic BEN areas in Romania and Serbia, and lignite and bituminous coals from nonendemic regions in Romania and the USA. Room temperature, hot water bath, and Soxhlet aqueous extraction experiments were conducted between 25 and 80 °C, and from 5 to 128 days in duration. A greater number of organic compounds and in higher concentrations were present in all three types of leaching experiments involving endemic area Pliocene lignite samples compared to all other coals examined. A BEN causing molecule or molecules may be among phenols, PAHs, benzenes, and/or lignin degradation compounds. The proposed transport pathway of the Pliocene lignite hypothesis for organic compound exposure from endemic area Pliocene lignite coals to well and spring drinking water, is likely. Aromatic compounds leached by groundwater from Pliocene lignite deposits in the vicinity of endemic BEN areas may play a role in the etiology of the disease. A better understanding of organic compounds leached by groundwater from Pliocene lignite deposits may potentially lead to the identification and implementation of effective strategies for the prevention of exposure to the causative agent(s) for BEN, and in turn, prevention of the disease.
-
Maharaj, S V M
2014-01-01
Balkan endemic nephropathy (BEN) is a chronic, tubulointerstitial renal disease often accompanied by urothelial cancer that has a lethality of nearly 100%. One of the many factors that have been proposed to play an etiological role in BEN is exposure to organic compounds from Pliocene lignite coal deposits via the drinking water in endemic areas. The objective of this study was to systematically evaluate the role of the tenets of the Pliocene lignite hypothesis in the etiology of BEN in order to provide an improved understanding of the hypothesis for colleagues and patients alike. A comprehensive compilation of the possible limitations of the hypothesis, with each limitation addressed in turn is presented. The Pliocene lignite hypothesis can best account for, is consistent with, or has the potential to explain the evidence associated with the myriad of factors related to BEN. Residents of endemic areas are exposed to complex mixtures containing hundreds of organic compounds at varying doses and their potentially more toxic (including nephrotoxic) and/or carcinogenic metabolites; however, a multifactorial etiology of BEN appears most likely.
-
Maharaj, S V M
2014-01-01
Background: Balkan endemic nephropathy (BEN) is a chronic, tubulointerstitial renal disease often accompanied by urothelial cancer that has a lethality of nearly 100%. Introduction: One of the many factors that have been proposed to play an etiological role in BEN is exposure to organic compounds from Pliocene lignite coal deposits via the drinking water in endemic areas. Objectives: The objective of this study was to systematically evaluate the role of the tenets of the Pliocene lignite hypothesis in the etiology of BEN in order to provide an improved understanding of the hypothesis for colleagues and patients alike. Methods: A comprehensive compilation of the possible limitations of the hypothesis, with each limitation addressed in turn is presented. Results: The Pliocene lignite hypothesis can best account for, is consistent with, or has the potential to explain the evidence associated with the myriad of factors related to BEN. Conclusions: Residents of endemic areas are exposed to complex mixtures containing hundreds of organic compounds at varying doses and their potentially more toxic (including nephrotoxic) and/or carcinogenic metabolites; however, a multifactorial etiology of BEN appears most likely. PMID:24075451
-
Pavlovic, N.M.; Orem, W.H.; Tatu, C.A.; Lerch, H.E.; Bunnell, J.E.; Feder, G.L.; Kostic, E.N.; Ordodi, V.L.
2008-01-01
Balkan endemic nephropathy (BEN) occurs in Serbia, Bulgaria, Romania, Bosnia and Herzegovina, and Croatia. BEN has been characterized as a chronic, slowly progressive renal disease of unknown etiology. In this study, we examined the influence of soluble organic compounds in drinking water leached from Pliocene lignite from BEN-endemic areas on plasma lecithin-cholesterol acyltransferase (LCAT) activity. We found that changes for all samples were the most prominent for the dilution category containing 90% plasma and 10% of diluting media. Water samples from BEN villages from Serbia and Romania showed higher LCAT inhibiting activity (p = 0.02) and (p = 0.003), respectively, compared to deionised water and non-endemic water. A secondary LCAT deficiency could result from this inhibitory effect of the organic compounds found in endemic water supplies and provide an ethiopathogenic basis for the development of BEN in the susceptible population. ?? 2007 Elsevier Ltd. All rights reserved.
-
Orem, W.H.; Feder, G.L.; Finkelman, R.B.
1999-01-01
Balkan endemic nephropathy (BEN) is a fatal kidney disease that is known to occur only in clusters of villages in alluvial valleys of tributaries of the Danube River in Bulgaria, Romania, Yugoslavia, Bosnia, and Croatia. The confinement of this disease to a specific geographic area has led to speculation that an environmental factor may be involved in the etiology of BEN. Numerous environmental factors have been suggested as causative agents for producing BEN, including toxic metals in drinking water, metal deficiency in soils of BEN areas, and environmental mycotoxins to name a few. These hypotheses have either been disproved or have failed to conclusively demonstrate a connection to the etiology of BEN, or the clustering of BEN villages. In previous work, we observed a distinct geographic relationship between the distribution of Pliocene lignites in the Balkans and BEN villages. We hypothesized that the long-term consumption of well water containing toxic organic compounds derived from the leaching of nearby Pliocene lignites by groundwater was a primary factor in the etiology of BEN. In our current work, chemical analysis using 13C nuclear magnetic resonance (13CNMR) spectroscopy indicated a high degree of organic functionality in Pliocene lignite from the Balkans, and suggested that groundwater can readily leach organic matter from these coal beds. Semi-quantitative gas chromatography/mass spectroscopy analysis of solvent extracts of groundwater from shallow wells in BEN villages indicated the presence of potentially toxic aromatic compounds, such as napthalene, fluorene, phenanthrene, and pyrene at concentrations in the ppb range. Laboratory leaching of Balkan Pliocene lignites with distilled water yielded soluble organic matter (> 500 MW) containing large amounts of aromatic structures similar to the simple/discrete aromatic compounds detected in well water from BEN villages. These preliminary results are permissive of our hypothesis and suggest that further
-
Stoev, Stoycho D
2017-01-05
The spreading of mycotoxic nephropathy in animals/humans was studied. The possible etiological causes provoking this nephropathy were carefully reviewed and analyzed. The natural content of the most frequent nephrotoxic mycotoxins in target feedstuffs/foods were investigated, in addition to their significance for development of renal damages in endemic areas. An estimation of the level of exposure of humans to the nephrotoxic mycotoxin, ochratoxin A (OTA), is made. The possible synergism or additive effects between some target mycotoxins in the development of nephropathy is also covered. The significance of joint mycotoxin interaction and masked mycotoxins, in addition to some newly isolated fungal toxic agents in the complicated etiology of mycotoxic nephropathy ranged in Balkan countries is discussed. The importance of some target fungal species which can induce kidney damages was evaluated. The morphological/ultrastructural, functional and toxicological similarities between human and animal nephropathy are studied. The possible hazard of low content of combinations of some target mycotoxins in food or feedstuff ingested by pigs, chickens or humans under natural conditions is evaluated and a risk assessment was made. Some different but more effective manners of prophylaxis and/or prevention against OTA contamination of feedstuffs/foods are suggested. A survey was made in regard to the best possible ways of veterinary hygiene control of OTA-exposed animals at slaughter time for preventing the entrance of OTA in commercial feedstuffs/food channels with a view to reduce the possible health hazard for humans. The economic efficacy and applicability of such preventive measures is additionally discussed and some practical suggestions are made. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
-
Could Disappearance of Endemic (Balkan) Nephropathy Be Expected in Forthcoming Decades?
Cvitković, Ante; Vuković-Lela, Ivana; Edwards, Karen L.; Karanović, Sandra; Jurić, Dragana; Čvorišćec, Dubravka; Fuček, Mirjana; Jelaković, Bojan
2012-01-01
Background/Aims An epidemiological survey of endemic nephropathy (EN) was performed in endemic Croatian areas and the current prevalence was compared to that reported for the same villages several decades ago. Methods A total of 2,487 adult farmers from 6 endemic villages and 3 non-endemic villages were enrolled. An extensive epidemiological questionnaire, clinical examination and laboratory analyses of blood and urine were performed. According to the modified WHO criteria, participants were classified into diseased, suspected of having EN, and those at risk of developing EN. Results The overall prevalence of EN in the Croatian areas was 1.0%, ranging between 0.3 and 2.3% in different villages. Those suspected of having EN amounted to 3.9%. In the endemic villages a decreasing trend in the prevalence of EN was observed comparable to the results obtained in previous surveys. It is interesting to note that no EN patients were recorded in the endemic village of Dubočac. Conclusion The prevalence of EN in the endemic Croatian areas appears to be decreasing. For the first time, we failed to detect any EN patients in a village that was previously considered endemic, which might indicate that EN is diminishing. PMID:22116163
-
Mantle, Peter; Modalca, Mirela; Nicholls, Andrew; Tatu, Calin; Tatu, Diana; Toncheva, Draga
2011-01-01
1H NMR spectroscopy of urine has been applied to exploring metabolomic differences between people diagnosed with Balkan endemic nephropathy (BEN), and treated by haemodialysis, and those without overt renal disease in Romania and Bulgaria. Convenience sampling was made from patients receiving haemodialysis in hospital and healthy controls in their village. Principal component analysis clustered healthy controls from both countries together. Bulgarian BEN patients clustered separately from controls, though in the same space. However, Romanian BEN patients not only also clustered away from controls but also clustered separately from the BEN patients in Bulgaria. Notably, the urinary metabolomic data of two people sampled as Romanian controls clustered within the Romanian BEN group. One of these had been suspected of incipient symptoms of BEN at the time of selection as a ‘healthy’ control. This implies, at first sight, that metabolomic analysis can be predictive of impending morbidity before conventional criteria can diagnose BEN. Separate clustering of BEN patients from Romania and Bulgaria could indicate difference in aetiology of this particular silent renal atrophy in different geographic foci across the Balkans. PMID:22069742
-
Toncheva, D.; Mihailova-Hristova, M.; Vazharova, R.; Staneva, R.; Karachanak, S.; Dimitrov, P.; Simeonov, V.; Ivanov, S.; Balabanski, L.; Serbezov, D.; Malinov, M.; Stefanovic, V.; Čukuranović, R.; Polenakovic, M.; Jankovic-Velickovic, L.; Djordjevic, V.; Jevtovic-Stoimenov, T.; Plaseska-Karanfilska, D.; Galabov, A.; Djonov, V.; Dimova, I.
2014-01-01
Balkan endemic nephropathy (BEN) is a familial chronic tubulointerstitial disease with insidious onset and slow progression leading to terminal renal failure. The results of molecular biological investigations propose that BEN is a multifactorial disease with genetic predisposition to environmental risk agents. Exome sequencing of 22 000 genes with Illumina Nextera Exome Enrichment Kit was performed on 22 DNA samples (11 Bulgarian patients and 11 Serbian patients). Software analysis was performed via NextGene, Provean, and PolyPhen. The frequency of all annotated genetic variants with deleterious/damaging effect was compared with those of European populations. Then we focused on nonannotated variants (with no data available about them and not found in healthy Bulgarian controls). There is no statistically significant difference between annotated variants in BEN patients and European populations. From nonannotated variants with more than 40% frequency in both patients' groups, we nominated 3 genes with possible deleterious/damaging variants—CELA1, HSPG2, and KCNK5. Mutant genes (CELA1, HSPG2, and KCNK5) in BEN patients encode proteins involved in basement membrane/extracellular matrix and vascular tone, tightly connected to process of angiogenesis. We suggest that an abnormal process of angiogenesis plays a key role in the molecular pathogenesis of BEN. PMID:24949484
-
Barta, Frantisek; Levova, Katerina; Hodek, Petr; Schmeiser, Heinz H; Arlt, Volker M; Stiborova, Marie
2015-01-01
Balkan endemic nephropathy (BEN) is a chronic progressive fibrosis associated with upper urothelial carcinoma (UUC). Aetiology of BEN is still not fully explained. Although carcinogenic aristolochic acid I (AAI) was proven as the major cause of BEN/UUC, this nephropathy is considered to be multifactorial. Hence, we investigated whether other factors considered as potential causes of BEN [a mycotoxin ochratoxin A (OTA), Cd, Pb, Se and As ions and organic compounds (i.e. phthalates) released from lignite deposits in BEN areas] can influence detoxication of AAI, whose concentrations are crucial for BEN development. Oxidation of AAI to 8-hydroxyaristolochic acid I (AAIa) in the presence of Cd, Pb, Se, As ions, dibutylphthalate (DBP), butylbenzylphthalate (BBP), bis(2-ethylhexyl)phthalate (DEHP) and OTA by rat liver microsomes was determined by HPLC. Only OTA, cadmium and selenium ions, and BBP inhibited AAI oxidation by rat liver microsomes. These compounds also inhibited activities of CYP1A1 and/or CYP2C6/11 catalysing AAI demethylation in rat livers. Therefore, these CYP inhibitions can be responsible for a decrease in AAIa formation. When the combined effects of these compounds were investigated, the most efficient inhibition was caused by OTA combined with BBP and selenium ions. The results show low effects of BBP, cadmium and selenium ions, and/or their combinations on AAI detoxication. No effects were produced by the other metal ions (Pb, As) and phthalates DBP and DEHP. This finding suggests that they do not influence AAI-mediated BEN development. In contrast, OTA might influence this process, by inhibition of AAI detoxication.
-
Stoev, S D; Dutton, M F; Njobeh, P B; Mosonik, J S; Steenkamp, P A
2010-01-01
Spontaneous nephropathy in Bulgaria, which is observed frequently during meat inspection and which differs morphologically from the classical description of mycotoxic porcine/chicken nephropathy as made in Denmark, was found to have a multi-mycotoxic aetiology being mainly provoked by a combined effect of ochratoxin A, penicillic acid and fumonisin B1 in addition to a not-yet-known metabolite. Mean contamination levels of ochratoxin A were consecutively low (188.8 and 376.4 microg kg(-1)) in contrast to high contamination levels of fumonisin B1 (5564.1 and 3254.5 microg kg(-1)) and penicillic acid (838.6 and 904.9 microg kg(-1)) for 2006 and 2007, respectively. Some other mycotoxins with lower importance such as citrinin, penitrem A, etc., may also influence clinicopathological picture of this nephropathy. A heavy contamination with Gibberella fujikuroi var. moniliformis (Fusarium verticillioides) and Penicillium aurantiogriseum complex (mainly Penicillium polonicum) was observed in almost all examined feed samples coming from pig and chick farms with nephropathy problems from Bulgaria. In contrast, low contamination with Aspergillus ochraceus, Penicillium verrucosum and Penicillium citrinum was observed in the same feed samples and these species were isolated as very rare components of the mycobiota.
-
Matic, Marija; Dragicevic, Biljana; Pekmezovic, Tatjana; Suvakov, Sonja; Savic-Radojevic, Ana; Pljesa-Ercegovac, Marija; Dragicevic, Dejan; Smiljic, Jelena; Simic, Tatjana
2016-09-01
Balkan endemic nephropathy (BEN) is a chronic familial form of interstitial nephritis that might eventually lead to end stage renal disease. This nephropathy affects individuals living along of the Danube River and its tributaries in Serbia, Bosnia, Croatia, Bulgaria and Romania. The increased incidence of urinary tract tumors in the BEN areas is well described, but its specific genetic predisposition is still unclear. Certain nephrocarcinogenic compounds, including those associated with BEN, are metabolized by glutathione S-transferase (GST) superfamily of phase II detoxication enzymes. Importantly, the GST-mediated detoxification may result in formation of more toxic compounds. We examined the association of common GST polymorphisms and bladder cancer (BC) risk in individuals from BEN areas in Serbia. A hospital-based case-control study included 201 BC cases (67 from BEN region) and 122 controls. Each polymorphism was identified by a PCR-based method. Individuals from BEN region with low-expression GSTA1 genotype (AB+BB) exhibited a 2.6-fold higher BC risk compared to those with GSTA1 (AA) genotype who were from non-BEN region (OR = 2.60, p = 0.015). In contrast, carriers of GSTM1-active genotype from BEN region had a 2.9-fold increased BC risk compared to those with GSTM1-active genotype from non-BEN region (OR = 2.90, p = 0.010). Likewise, carriers with GSTT1-active genotype from BEN region exhibited 2.1-fold higher BC risk compared to those from non-BEN region with GSTT1-active genotype (OR = 2.10, p = 0.027). Thus, common polymorphisms in GSTA1, GSTM1 and GSTT1 are associated with susceptibility to BC in individuals from BEN areas of Serbia.
-
Reljic, Zorica; Zlatovic, Mario; Savic-Radojevic, Ana; Pekmezovic, Tatjana; Djukanovic, Ljubica; Matic, Marija; Pljesa-Ercegovac, Marija; Mimic-Oka, Jasmina; Opsenica, Dejan; Simic, Tatjana
2014-01-01
Although recent data suggest aristolochic acid as a putative cause of Balkan endemic nephropathy (BEN), evidence also exists in favor of ochratoxin A (OTA) exposure as risk factor for the disease. The potential role of xenobiotic metabolizing enzymes, such as the glutathione transferases (GSTs), in OTA biotransformation is based on OTA glutathione adducts (OTHQ-SG and OTB-SG) in blood and urine of BEN patients. We aimed to analyze the association between common GSTA1, GSTM1, GSTT1, and GSTP1 polymorphisms and BEN susceptibility, and thereafter performed an in silico simulation of particular GST enzymes potentially involved in OTA transformations. GSTA1, GSTM1, GSTT1 and GSTP1 genotypes were determined in 207 BEN patients and 138 non-BEN healthy individuals from endemic regions by polymerase chain reaction (PCR). Molecular modeling in silico was performed for GSTA1 protein. Among the GST polymorphisms tested, only GSTA1 was significantly associated with a higher risk of BEN. Namely, carriers of the GSTA1*B gene variant, associated with lower transcriptional activation, were at a 1.6-fold higher BEN risk than those carrying the homozygous GSTA1*A/*A genotype (OR = 1.6; p = 0.037). In in silico modeling, we found four structures, two OTB-SG and two OTHQ-SG, bound in a GSTA1 monomer. We found that GSTA1 polymorphism was associated with increased risk of BEN, and suggested, according to the in silico simulation, that GSTA1-1 might be involved in catalyzing the formation of OTHQ-SG and OTB-SG conjugates. PMID:25111321
-
Aristolochic acid nephropathy: Harbinger of a global iatrogenic disease.
Grollman, Arthur P
2013-01-01
This review constitutes an overview of our investigations of aristolochic acid nephropathy, a chronic kidney disease associated with carcinomas of the upper urinary tract. Our studies began by confirming the hypothesis that chronic dietary poisoning by aristolochic acid was responsible for endemic (Balkan) nephropathy. A unique TP53 mutational signature in urothelial tumors and the presence of aristolactam-DNA adducts in the renal cortex, defined in the course of this research, proved to be robust biomarkers of exposure to this potent nephrotoxin and human carcinogen. Armed with this information, we used molecular epidemiologic approaches and novel mechanistic information to establish the causative role of aristolochic acid in upper urinary tract carcinoma in Taiwan, where one-third of the population had been prescribed herbal remedies containing Aristolochia, and the recorded incidence of upper urinary tract cancers is the highest in the world. As traditional Chinese medicine is practiced similarly in Taiwan and China, it is likely that upper urinary tract carcinomas and their attendant aristolochic acid nephropathy are prevalent in China and other Asian countries where Aristolochia herbs have been used for centuries in the treatment and prevention of disease, creating a potential public health problem of considerable magnitude. Copyright © 2012 Wiley Periodicals, Inc.
-
Nikolić, Biljana; Ristić, Mihailo; Tešević, Vele; Marin, Petar D; Bojović, Srdjan
2011-12-01
Terpenes are often used as ecological and chemotaxonomic markers of plant species, as well as for estimation of geographic variability. Essential oils of relic and Balkan endemic/subendemic conifers, Picea omorika, Pinus heldreichii, and P. peuce, in central part of Balkan Peninsula (Serbia and Montenegro), on the level of terpene classes and common terpene compounds were investigated. In finding terpene combinations, which could show the best diversity between species and their natural populations, several statistical methods were applied. Apart from the content of different terpene classes (P. omorika has the most abundant O-containing monoterpenes and sesquiterpenes; P. heldreichii and P. peuce have the largest abundance of sesquiterpene and monoterpene hydrocarbons, resp.), the species are clearly separated according to terpene profile with 22 common compounds. But, divergences in their populations were established only in combination of several compounds (specific for each species), and they were found to be the results of geomorphologic, climatic, and genetic factors. We found similarities between investigated species and some taxa from literature with respect to terpene composition, possibly due to hybridization and phylogenetic relations. Obtained results are also important regarding to chemotaxonomy, biogeography, phylogeny, and evolution of these taxa. Copyright © 2011 Verlag Helvetica Chimica Acta AG, Zürich.
-
Mycotoxic nephropathy in pigs*
Elling, F.; Møller, T.
1973-01-01
In Denmark a nephropathy in pigs characterized by tubular atrophy and interstitial fibrosis has been identified frequently during the last 5 decades in the course of meat inspection in slaughterhouses. The disease was first described by Larsen, who recognized the connexion between feeding mouldy rye to pigs and the development of the nephropathy. In this study kidneys were examined from 19 pigs coming from a farm with an outbreak of nephropathy. The barley fed to the pigs was contaminated with the mycotoxin ochratoxin A. Histological examination revealed different degrees of change ranging from slight regressive changes in the tubular epithelium and periglomerular and interstitial fibrosis to tubular atrophy, thickened basement membranes, glomerular sclerosis, and marked fibrosis. These differences were considered to be due to differences in the length of time of exposure to the mouldy barley and differences in the amount of mycotoxin consumed by the individual pig. However, it will be necessary to carry out experiments using crystalline ochratoxin A in order to prove such a relationship. Mycotoxins have also been suggested as etiological factors in Balkan nephropathy in man, which in the initial stages is characterized by tubular lesions similar to those seen in mycotoxic nephropathy in pigs. ImagesFig. 1Fig. 2Fig. 7Fig. 8Fig. 9Fig. 3Fig. 4Fig. 5Fig. 6Fig. 10Fig. 11 PMID:4546872
-
Fuček, Mirjana; Dika, Živka; Karanović, Sandra; Vuković Brinar, Ivana; Premužić, Vedran; Kos, Jelena; Cvitković, Ante; Mišić, Maja; Samardžić, Josip; Rogić, Dunja; Jelaković, Bojan
2018-02-15
Chronic kidney disease (CKD) is a significant public health problem and it is not possible to precisely predict its progression to terminal renal failure. According to current guidelines, CKD stages are classified based on the estimated glomerular filtration rate (eGFR) and albuminuria. Aims of this study were to determine the reliability of predictive equation in estimation of CKD prevalence in Croatian areas with endemic nephropathy (EN), compare the results with non-endemic areas, and to determine if the prevalence of CKD stages 3-5 was increased in subjects with EN. A total of 1573 inhabitants of the Croatian Posavina rural area from 6 endemic and 3 non-endemic villages were enrolled. Participants were classified according to the modified criteria of the World Health Organization for EN. Estimated GFR was calculated using Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). The results showed a very high CKD prevalence in the Croatian rural area (19%). CKD prevalence was significantly higher in EN then in non EN villages with the lowest eGFR value in diseased subgroup. eGFR correlated significantly with the diagnosis of EN. Kidney function assessment using CKD-EPI predictive equation proved to be a good marker in differentiating the study subgroups, remained as one of the diagnostic criteria for EN.
-
Fuček, Mirjana; Dika, Živka; Karanović, Sandra; Vuković Brinar, Ivana; Premužić, Vedran; Kos, Jelena; Cvitković, Ante; Mišić, Maja; Samardžić, Josip; Rogić, Dunja; Jelaković, Bojan
2017-01-01
Introduction Chronic kidney disease (CKD) is a significant public health problem and it is not possible to precisely predict its progression to terminal renal failure. According to current guidelines, CKD stages are classified based on the estimated glomerular filtration rate (eGFR) and albuminuria. Aims of this study were to determine the reliability of predictive equation in estimation of CKD prevalence in Croatian areas with endemic nephropathy (EN), compare the results with non-endemic areas, and to determine if the prevalence of CKD stages 3-5 was increased in subjects with EN. Materials and methods A total of 1573 inhabitants of the Croatian Posavina rural area from 6 endemic and 3 non-endemic villages were enrolled. Participants were classified according to the modified criteria of the World Health Organization for EN. Estimated GFR was calculated using Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). Results The results showed a very high CKD prevalence in the Croatian rural area (19%). CKD prevalence was significantly higher in EN then in non EN villages with the lowest eGFR value in diseased subgroup. Conclusions eGFR correlated significantly with the diagnosis of EN. Kidney function assessment using CKD-EPI predictive equation proved to be a good marker in differentiating the study subgroups, remained as one of the diagnostic criteria for EN. PMID:29187794
-
Kutnjak, Denis; Kuttner, Michael; Niketić, Marjan; Dullinger, Stefan; Schönswetter, Peter; Frajman, Božo
2014-09-01
The Balkans are a major European biodiversity hotspot, however, almost nothing is known about processes of intraspecific diversification of the region's high-altitude biota and their reaction to the predicted global warming. To fill this gap, genome size measurements, AFLP fingerprints, plastid and nuclear sequences were employed to explore the phylogeography of Cerastium dinaricum. Range size changes under future climatic conditions were predicted by niche-based modeling. Likely the most cold-adapted plant endemic to the Dinaric Mountains in the western Balkan Peninsula, the species has conservation priority in the European Union as its highly fragmented distribution range includes only few small populations. A deep phylogeographic split paralleled by divergent genome size separates the populations into two vicariant groups. Substructure is pronounced within the southeastern group, corresponding to the area's higher geographic complexity. Cerastium dinaricum likely responded to past climatic oscillations with altitudinal range shifts, which, coupled with high topographic complexity of the region and warmer climate in the Holocene, sculptured its present fragmented distribution. Field observations revealed that the species is rarer than previously assumed and, as shown by modeling, severely endangered by global warming as viable habitat was predicted to be reduced by more than 70% by the year 2080. Copyright © 2014 Elsevier Inc. All rights reserved.
-
Vishnevskaya, Maria S.; Saifitdinova, Alsu F.; Lukhtanov, Vladimir A.
2016-01-01
Abstract The Balkan Peninsula represents one of the hottest biodiversity spots in Europe. However, the invertebrate fauna of this region is still insufficiently investigated, even in respect of such well-studied organisms as Lepidoptera. Here we use a combination of chromosomal, molecular and morphological markers to rearrange the group of so-called anomalous blue butterflies (also known as ‘brown complex’ of the subgenus Agrodiaetus Hübner, [1822] and as the Polyommatus (Agrodiaetus) admetus (Esper, 1783) species group) and to reveal its cryptic taxonomic structure. We demonstrate that Polyommatus aroaniensis (Brown, 1976) is not as widespread in the Balkans as was previously thought. In fact, it has a dot-like distribution range restricted to the Peloponnese Peninsula in South Greece. Polyommatus orphicus Kolev, 2005 is not as closely related to the Turkish species Polyommatus dantchenkoi (Lukhtanov & Wiemers, 2003) as was supposed earlier. Instead, it is a Balkan endemic represented by two subspecies: Polyommatus orphicus orphicus (Bulgaria) and Polyommatus orphicus eleniae Coutsis & De Prins, 2005 (Northern Greece). Polyommatus ripartii (Freyer, 1830) is represented in the Balkans by an endemic subspecies Polyommatus ripartii pelopi. The traditionally recognized Polyommatus admetus (Esper, 1783) is shown to be a heterogeneous complex and is divided into Polyommatus admetus sensu stricto (the Balkans and west Turkey) and Polyommatus yeranyani (Dantchenko & Lukhtanov, 2005) (east Turkey, Armenia, Azerbaijan and Iran). Polyommatus nephohiptamenos (Brown & Coutsis, 1978) is confirmed to be a species with a dot-like distribution range in Northern Greece. Finally, from Central Greece (Timfristos and Parnassos mountains) we describe Polyommatus timfristos Lukhtanov, Vishnevskaya & Shapoval, sp. n. which differs by its haploid chromosome number (n=38) from the closely related and morphologically similar Polyommatus aroaniensis (n=47-48) and Polyommatus orphicus (n
-
Unraveling the Mystery of an Environmental Disease
DOE Office of Scientific and Technical Information (OSTI.GOV)
Grollman, Arthur
For many years, residents of farming villages along the Danube River basin suffered from a fatal kidney disease and an associated urinary tract cancer. The cause of the disease remained a mystery for more than 50 years. Recently, however, Arthur Grollman and his colleagues have determined that home-baked bread is implicated in the disease, known as Balkan endemic nephropathy.
-
Comparative analysis of diabetic nephropathy and non-diabetic nephropathy disease.
Chen, Qiuxiang; Zhu, Aimin; Wang, Junsheng; Huan, Xuelai
2017-12-01
Clinical symptoms of diabetic nephropathy patients and non-diabetic nephropathy are compared and analyzed, hemodialysis effect and quality of life of two kinds of nephrotic patients are analyzed. Respectively extract 1300 cases of diabetic nephropathy and non-diabetic nephropathy patients admitted to different hospitals during December 2011-December 2014. Based on whether the patient suffers from diabetes, they were divided into diabetic group and control group. Hemodialysis of two groups of patients were followed up to observe effectiveness of blood treatment, and complications were observed after one year of follow-up. Hematodialysis effectiveness of diabetic nephropathy patients is significantly lower than that of non-diabetic nephropathy group. After 1 year's follow-up, it can be found that survival rate of diabetic nephropathy patients is much lower than that of control group. In statistical comparison of data involved in the two groups of patients, P < 0.05, the difference is statistically significant. Treatment effect of diabetic nephropathy patients is relatively poor compared to that of non-diabetic patients. In clinics, management and prevention of diabetic patients should be strengthened to avoid complication of nephropathy which brings serious injury to patients.
-
Psonis, Nikolaos; Antoniou, Aglaia; Karameta, Emmanouela; Leaché, Adam D; Kotsakiozi, Panayiota; Darriba, Diego; Kozlov, Alexey; Stamatakis, Alexandros; Poursanidis, Dimitris; Kukushkin, Oleg; Jablonski, Daniel; Crnobrnja-Isailović, Jelka; Gherghel, Iulian; Lymberakis, Petros; Poulakakis, Nikos
2018-08-01
The Balkan Peninsula constitutes a biodiversity hotspot with high levels of species richness and endemism. The complex geological history of the Balkans in conjunction with the climate evolution are hypothesized as the main drivers generating this biodiversity. We investigated the phylogeography, historical demography, and population structure of closely related wall-lizard species from the Balkan Peninsula and southeastern Europe to better understand diversification processes of species with limited dispersal ability, from Late Miocene to the Holocene. We used several analytical methods integrating genome-wide SNPs (ddRADseq), microsatellites, mitochondrial and nuclear DNA data, as well as species distribution modelling. Phylogenomic analysis resulted in a completely resolved species level phylogeny, population level analyses confirmed the existence of at least two cryptic evolutionary lineages and extensive within species genetic structuring. Divergence time estimations indicated that the Messinian Salinity Crisis played a key role in shaping patterns of species divergence, whereas intraspecific genetic structuring was mainly driven by Pliocene tectonic events and Quaternary climatic oscillations. The present work highlights the effectiveness of utilizing multiple methods and data types coupled with extensive geographic sampling to uncover the evolutionary processes that shaped the species over space and time. Copyright © 2018 Elsevier Inc. All rights reserved.
-
Balkan Identity: Changing Self-Images of the South Slavs
ERIC Educational Resources Information Center
Saric, Ljiljana
2004-01-01
This paper provides an analysis of texts containing the noun "the Balkans" and the adjective "Balkan" in a small corpus of approximately 80 journalistic texts from different south Slavic regions currently available online. The texts were published over the last 10 years. The term "the Balkans" and its derivations…
-
Papper, S
1980-01-01
There are many causes of interstitial nephritis other than pyelonephritis. The term interstitial nephritis does not connote a single etiologic or pathogenetic mechanism; it rather arbitrarily places together a wider variety of renal diseases that have a predilection for early and major involvement of the renal interstitium. The prototype of acute interstitial nephritis is acute pyelonephritis. In addition, there is a drug-related acute interstitial disease that is probably of immunological nature and usually reverses with discontinuance of the offending drug. Chronic interstitial nephritis includes many diverse illnesses. Nonobstructive pyelonephritis occurs but its prevalence is debated. Analgesic abuse nephropathy is not rare and is potentially reversible. Papillary necrosis has many causes and a wide spectrum of clinical presentations. Heavy metals, such as lead, cause interstitial nephritis. Balkan nephropathy occurs in an endemic area and although not bacterial in origin is of unknown cause.
-
European Enlargement and the Integration of the Western Balkans
2003-06-01
Balkans 6 . AUTHOR(S) Leonard Demi 5. FUNDING NUMBERS 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Naval Postgraduate School...7th centuries, had the greatest effect on the subsequent ethnic composition of the area. 6 Jelavich, B., History of the Balkans: 20th Century, v...republic. The people were disappointed and demonstrated [Lee, M., “Kosovo between Yugoslavia and Albania,” New Left Review, 6 map of the Balkans
-
Medicine in Balkans during the Roman Period
Baykan, Daniş
2017-01-01
The aim of this study is to investigate the archaeological finds to enlighten the medical methods of treatments and operations applied in Balkans during Roman Period. Some independent local and regional find groups, taken from existing publications will be grouped together and a holistic point-of-view will be taken against medicine in Balkan Geography during Roman Period. Due to basic differences it contained, the data before Roman Period are excluded. Most of Greece and Aegean Islands are also excluded since the topic selected is “Medicine of Roman Period.” Greece and Aegean Islands should be evaluated in another study in connection with West Anatolia which is closer than the Balkan Geography in terms of social relations. The spread of medical tools in Balkans during Roman Period is concentrated around military garrisons, and in settlements built around military pathways, and in settlements containing an amphitheater associated with gladiators. This spread is verified by the studies on Bulgaria in general. The data is also compatible with the assertion suggesting that the amount of application of pharmaceutical treatment increases when one moves away from the military centres. PMID:28552838
-
Medicine in Balkans during the Roman Period.
Baykan, Daniş
2017-08-04
The aim of this study is to investigate the archaeological finds to enlighten the medical methods of treatments and operations applied in Balkans during Roman Period. Some independent local and regional find groups, taken from existing publications will be grouped together and a holistic point-of-view will be taken against medicine in Balkan Geography during Roman Period. Due to basic differences it contained, the data before Roman Period are excluded. Most of Greece and Aegean Islands are also excluded since the topic selected is "Medicine of Roman Period." Greece and Aegean Islands should be evaluated in another study in connection with West Anatolia which is closer than the Balkan Geography in terms of social relations. The spread of medical tools in Balkans during Roman Period is concentrated around military garrisons, and in settlements built around military pathways, and in settlements containing an amphitheater associated with gladiators. This spread is verified by the studies on Bulgaria in general. The data is also compatible with the assertion suggesting that the amount of application of pharmaceutical treatment increases when one moves away from the military centres.
-
Li, Weiwei; Chan, Chi-Kong; Wong, Yee-Lam; Chan, K K Jason; Chan, Ho Wai; Chan, Wan
2018-10-30
Emerging evidence suggests that aristolochic acids (AA) produced naturally by a common weed Aristolochia clematitis in the cultivation fields is contaminating the food products in Balkan Peninsula and acting as the etiological agent in the development of Balkan endemic nephropathy. In this study, we investigated the combined use of natural anti-oxidative "food additives" and different cooking methods to find a solution for the widespread contamination of AA in food products. The results indicated that the addition of healthy dietary supplements (such as cysteine, glutathione, ascorbic acid, citric acid and magnesium) during cooking, is a highly efficient method in lowering the concentration of AA in the final food products. Because previous observation indicated one of the toxicological mechanisms by which AA exert its toxicity is to induce oxidative stress in internal organs, it is anticipated that these added anti-oxidants will also help to attenuate the nephrotoxicity of AA. Copyright © 2018 Elsevier Ltd. All rights reserved.
-
Li, Weiwei; Hu, Qin; Chan, Wan
2016-01-13
Emerging evidence has suggested aristolochic acids (AAs) are linked to the development of Balkan endemic nephropathy (BEN), a chronic renal disease affecting numerous farmers living in the Balkan peninsula. However, the pathway by which AAs enter the human food chain and cause kidney disease remains poorly understood. Using our previously developed analytical method with high sensitivity and selectivity (Chan, W.; Lee, K. C.; Liu, N.; Cai, Z. J. Chromatogr. A 2007, 1164, 113-119), we quantified AAs in lettuce, tomato, and spring onion grown in AA-contaminated soil and culture medium. Our study revealed that AAs were being taken up from the soil and bioaccumulated in food crops in a time- and dose-dependent manner. To the best of our knowledge, this study is the first to identify one of the possible pathways by which AAs enter our food chain to cause chronic food poisoning. Results also demonstrated that AAs were resistant to the microbial activity of the soil/water.
-
Olšavská, Katarína; Slovák, Marek; Marhold, Karol; Štubňová, Eliška; Kučera, Jaromír
2016-11-01
The Balkan Peninsula is one of the most important centres of plant diversity in Europe. Here we aim to fill the gap in the current knowledge of the evolutionary processes and factors modelling this astonishing biological richness by applying multiple approaches to the Cyanus napulifer group. To reconstruct the mode of diversification within the C. napulifer group and to uncover its relationships with potential relatives with x = 10 from Europe and Northern Africa, we examined variation in genetic markers (amplified fragment length polymorphisms [AFLPs]; 460 individuals), relative DNA content (4',6-diamidino-2-phenylindole [DAPI] flow cytometry, 330 individuals) and morphology (multivariate morphometrics, 40 morphological characters, 710 individuals). To elucidate its evolutionary history, we analysed chloroplast DNA (cpDNA) sequences of the genus Cyanus deposited in the GenBank database. The AFLPs revealed a suite of closely related entities with variable levels of differentiation. The C. napulifer group formed a genetically well-defined unit. Samples outside the group formed strongly diversified and mostly species-specific genetic lineages with no further geographical patterns, often characterized also by a different DNA content. AFLP analysis of the C. napulifer group revealed extensive radiation and split it into nine allopatric (sub)lineages with varying degrees of congruence among genetic, DNA-content and morphological patterns. Genetic admixture was usually detected in contact zones between genetic lineages. Plastid data indicated extensive maintenance of ancestral variation across Cyanus perennials. The C. napulifer group is an example of a rapidly and recently diversified plant group whose genetic lineages have evolved in spatio-temporal isolation on the topographically complex Balkan Peninsula. Adaptive radiation, accompanied in some cases by long-term isolation and hybridization, has contributed to the formation of this species complex and its mosaic
-
How unique is the tiger beetle fauna (Coleoptera, Cicindelidae) of the Balkan Peninsula?
Jaskuła, Radomir
2011-01-01
Abstract The tiger beetle fauna of the Balkan Peninsula is one of the richest in Europe and includes 19 species or 41% of the European tiger beetle fauna. Assembled by their biogeographical origins, the Balkan tiger beetle species fall into 14 different groups that include, Mediterranean, Middle Oriental, Central Asiatic, Euro-Siberian, South and East European, Pannonian-Sarmatian, West Palaearctic, Turano-European and Afrotropico Indo-Mediterranean species. The Mediterranean Sclerophyl and the Pontian Steppe are the Balkan biogeographical provinces with the highest species richness, while the Balkan Highlands has the lowest Cicindelidae diversity. Most species are restricted to single habitat types in lowland areas of the Balkan Peninsula and only Calomera aulica aulica and Calomera littoralis nemoralis occur in respectively 3 and 4 different types of habitat. About 60% of all Balkan Cicindelidae species are found in habitats potentially endangered by human activity. PMID:21738429
-
Preservation of Scientific and Cultural Heritage in Balkan Countries
ERIC Educational Resources Information Center
Tonta, Yasar
2009-01-01
Purpose: The peoples living in the Balkan Peninsula over centuries have created a very rich cultural heritage and the constant political upheavals in the region have affected the development and preservation of their cultures. This paper aims to review the internet infrastructure and networked readiness levels of the Balkan countries, which are…
-
Microscale vicariance and diversification of Western Balkan caddisflies linked to karstification.
Previšić, Ana; Schnitzler, Jan; Kučinić, Mladen; Graf, Wolfram; Ibrahimi, Halil; Kerovec, Mladen; Pauls, Steffen U
2014-03-01
The karst areas in the Dinaric region of the Western Balkan Peninsula are a hotspot of freshwater biodiversity. Many investigators have examined diversification of the subterranean freshwater fauna in these karst systems. However, diversification of surface-water fauna remains largely unexplored. We assessed local and regional diversification of surface-water species in karst systems and asked whether patterns of population differentiation could be explained by dispersal-diversification processes or allopatric diversification following karst-related microscale vicariance. We analyzed mitochondrial cytochrome c oxidase subunit I (mtCOI) sequence data of 4 caddisfly species (genus Drusus ) in a phylogeographic framework to assess local and regional population genetic structure and Pliocene/Pleistocene history. We used BEAST software to assess the timing of intraspecific diversification of the target species. We compared climate envelopes of the study species and projected climatically suitable areas during the last glacial maximum (LGM) to assess differences in the species climatic niches and infer potential LGM refugia. The haplotype distribution of the 4 species (324 individuals from 32 populations) was characterized by strong genetic differentiation with few haplotypes shared among populations (16%) and deep divergence among populations of the 3 endemic species, even at local scales. Divergence among local populations of endemics often exceeded divergence among regional and continental clades of the widespread D. discolor . Major divergences among regional populations dated to 2.0 to 0.5 Mya. Species distribution model projections and genetic structure suggest that the endemic species persisted in situ and diversified locally throughout multiple Pleistocene climate cycles. The pattern for D. discolor was different and consistent with multiple invasions into the region. Patterns of population genetic structure and diversification were similar for the 3 regional
-
A Roadmap for Future Security in the Western Balkans
2012-03-22
and a specific cultural ambience.”5 In its historical background, the Balkan region was full of lasting frictions and security dilemmas. Probably...full moral , political, and diplomatic authority in a coherent and consistent way.”45 Although the EU has made a lot of organizational and... moral and pragmatic reasons toward the Western Balkan crisis in order to prevent the worst case scenario: escalating conflicts in Europe, and the
-
Islamic Revival in the Balkans
2006-03-01
Paperwork Reduction Project (0704-0188) Washington DC 20503. 1. AGENCY USE ONLY (Leave blank) 2. REPORT DATE March 2006 3. REPORT TYPE AND DATES...different from the US Global War on Terror strategic framework. 15. NUMBER OF PAGES 125 14. SUBJECT TERMS Balkans, Bosnia, Bulgaria, Global Salafi...
-
New formulae for estimating stature in the Balkans.
Ross, Ann H; Konigsberg, Lyle W
2002-01-01
Recent studies of secular change and allometry have observed differential limb proportions between the sexes, among and within populations. These studies suggest that stature prediction formulae developed from American Whites may be inappropriate for European populations. The purpose of this investigation is to present more appropriate stature prediction equations for use in the Balkans to aid present-day identifications of the victims of genocide. The reference sample totals 545 white males obtained from World War II data. The Eastern European sample totals 177 males and includes both Bosnian and Croatian victims of the recent war. Mean stature for Eastern Europeans was obtained from the literature. Results show that formulae based on Trotter and Gleser systematically underestimate stature in the Balkans. Because Eastern Europeans are taller than American Whites it is appropriate to use this as an "informative prior" that can be applied to future cases. This informative prior can be used in predictive formulae, since it is probably similar to the sample from which the Balkan forensic cases were drawn. Based on Bayes' Theorem new predictive stature formulae are presented for Eastern Europeans.
-
Record Balkan floods of 2014 linked to planetary wave resonance.
Stadtherr, Lisa; Coumou, Dim; Petoukhov, Vladimir; Petri, Stefan; Rahmstorf, Stefan
2016-04-01
In May 2014, the Balkans were hit by a Vb-type cyclone that brought disastrous flooding and severe damage to Bosnia and Herzegovina, Serbia, and Croatia. Vb cyclones migrate from the Mediterranean, where they absorb warm and moist air, to the north, often causing flooding in central/eastern Europe. Extreme rainfall events are increasing on a global scale, and both thermodynamic and dynamical mechanisms play a role. Where thermodynamic aspects are generally well understood, there is large uncertainty associated with current and future changes in dynamics. We study the climatic and meteorological factors that influenced the catastrophic flooding in the Balkans, where we focus on large-scale circulation. We show that the Vb cyclone was unusually stationary, bringing extreme rainfall for several consecutive days, and that this situation was likely linked to a quasi-stationary circumglobal Rossby wave train. We provide evidence that this quasi-stationary wave was amplified by wave resonance. Statistical analysis of daily spring rainfall over the Balkan region reveals significant upward trends over 1950-2014, especially in the high quantiles relevant for flooding events. These changes cannot be explained by simple thermodynamic arguments, and we thus argue that dynamical processes likely played a role in increasing flood risks over the Balkans.
-
Balkan brachicerous cattle - the first domesticated cattle in Europe.
Hristov, Peter; Sirakova, Daniela; Mitkov, Ivan; Spassov, Nikolai; Radoslavov, Georgi
2018-01-01
The present study aimed to compare mitochondrial diversity among Balkan Neolithic/Chalcolithic cattle and present day Shorthorn Rhodopean cattle (Busha) to throw a new insight into European cattle domestication. The results showed that both ancient- and present-day samples belonged to the macrohaplogroup T. From the 28 sequences (8 ancient and 20 modern), the T1 and T2 haplogroup represent about 3.6% (1/28; 1/28). The T3 haplogroup was with the highest frequency - 57% (16/28). Based on the SNPs on 16057A and 16133C, the new T6 haplogroup was proposed. This haplogroup represents 75% from the ancient and 20% from the present day Bulgarian brachicerous cattle population. The survey in GenBank data base did not find a similar motif, except for the recent Serbian Busha cattle. Overall, these results showed that: (i) The newly named T6 haplogroup is Balkan specific; (ii) The T6 haplogroup survives in present day Bulgarian rhodopean cattle; (iii) The Balkan brachicerous cattle is the oldest European cattle breed.
-
New insights into the origin and the genetic status of the Balkan donkey from Serbia.
Stanisic, L J; Aleksic, J M; Dimitrijevic, V; Simeunovic, P; Glavinic, U; Stevanovic, J; Stanimirovic, Z
2017-10-01
The Balkan donkey (Equus asinus L.) is commonly regarded as a large-sized, unselected, unstructured and traditionally managed donkey breed. We assessed the current genetic status of the three largest E. asinus populations in the central Balkans (Serbia) by analysing the variability of nuclear microsatellites and the mitochondrial (mtDNA) control region of 77 and 49 individuals respectively. We further analysed our mtDNA dataset along with 209 published mtDNA sequences of ancient and modern individuals from 19 European and African populations to provide new insights into the origin and the history of the Balkan donkey. Serbian donkey populations are highly genetically diverse at both the nuclear and mtDNA levels despite severe population decline. Traditional Balkan donkeys in Serbia are rather heterogeneous; we found two groups of individuals with similar phenotypic features, somewhat distinct nuclear backgrounds and different proportions of mtDNA haplotypes belonging to matrilineal Clades 1 and 2. Another group, characterized by larger body size, different coat colour, distinct nuclear gene pool and predominantly Clade 2 haplotypes, was delineated as the Banat donkey breed. The maternal landscape of the large Balkan donkey population is highly heterogeneous and more complex than previously thought. Given the two independent domestication events in donkeys, multiple waves of introductions into the Balkans from Greece are hypothesized. Clade 2 donkeys probably appeared in Greece prior to those belonging to Clade 1, whereas expansion and diversification of Clade 1 donkeys within the Balkans predated that of Clade 2 donkeys. © 2017 Stichting International Foundation for Animal Genetics.
-
3 CFR - Continuation of the National Emergency With Respect to the Western Balkans
Code of Federal Regulations, 2013 CFR
2013-01-01
... 3 The President 1 2013-01-01 2013-01-01 false Continuation of the National Emergency With Respect to the Western Balkans Presidential Documents Other Presidential Documents Notice of June 22, 2012 Continuation of the National Emergency With Respect to the Western Balkans On June 26, 2001, by Executive Order...
-
Furuichi, Kengo; Shimizu, Miho; Yuzawa, Yukio; Hara, Akinori; Toyama, Tadashi; Kitamura, Hiroshi; Suzuki, Yoshiki; Sato, Hiroshi; Uesugi, Noriko; Ubara, Yoshifumi; Hohino, Junichi; Hisano, Satoshi; Ueda, Yoshihiko; Nishi, Shinichi; Yokoyama, Hitoshi; Nishino, Tomoya; Kohagura, Kentaro; Ogawa, Daisuke; Mise, Koki; Shibagaki, Yugo; Makino, Hirofumi; Matsuo, Seiichi; Wada, Takashi
2018-06-01
The Japanese classification of diabetic nephropathy reflects the risks of mortality, cardiovascular events and kidney prognosis and is clinically useful. Furthermore, pathological findings of diabetic nephropathy are useful for predicting prognoses. In this study, we evaluated the characteristics of pathological findings in relation to the Japanese classification of diabetic nephropathy and their ability to predict prognosis. The clinical data of 600 biopsy-confirmed diabetic nephropathy patients were collected retrospectively from 13 centers across Japan. Composite kidney events, kidney death, cardiovascular events, all-cause mortality, and decreasing rate of estimated GFR (eGFR) were evaluated based on the Japanese classification of diabetic nephropathy. The median observation period was 70.4 (IQR 20.9-101.0) months. Each stage had specific characteristic pathological findings. Diffuse lesions, interstitial fibrosis and/or tubular atrophy (IFTA), interstitial cell infiltration, arteriolar hyalinosis, and intimal thickening were detected in more than half the cases, even in Stage 1. An analysis of the impacts on outcomes in all data showed that hazard ratios of diffuse lesions, widening of the subendothelial space, exudative lesions, mesangiolysis, IFTA, and interstitial cell infiltration were 2.7, 2.8, 2.7, 2.6, 3.5, and 3.7, respectively. Median declining speed of eGFR in all cases was 5.61 mL/min/1.73 m 2 /year, and the median rate of declining kidney function within 2 years after kidney biopsy was 24.0%. This study indicated that pathological findings could categorize the high-risk group as well as the Japanese classification of diabetic nephropathy. Further study using biopsy specimens is required to clarify the pathogenesis of diabetic kidney disease.
-
Reversal of Diabetic Nephropathy by a Ketogenic Diet
Poplawski, Michal M.; Mastaitis, Jason W.; Isoda, Fumiko; Grosjean, Fabrizio; Zheng, Feng; Mobbs, Charles V.
2011-01-01
Intensive insulin therapy and protein restriction delay the development of nephropathy in a variety of conditions, but few interventions are known to reverse nephropathy. Having recently observed that the ketone 3-beta-hydroxybutyric acid (3-OHB) reduces molecular responses to glucose, we hypothesized that a ketogenic diet, which produces prolonged elevation of 3-OHB, may reverse pathological processes caused by diabetes. To address this hypothesis, we assessed if prolonged maintenance on a ketogenic diet would reverse nephropathy produced by diabetes. In mouse models for both Type 1 (Akita) and Type 2 (db/db) diabetes, diabetic nephropathy (as indicated by albuminuria) was allowed to develop, then half the mice were switched to a ketogenic diet. After 8 weeks on the diet, mice were sacrificed to assess gene expression and histology. Diabetic nephropathy, as indicated by albumin/creatinine ratios as well as expression of stress-induced genes, was completely reversed by 2 months maintenance on a ketogenic diet. However, histological evidence of nephropathy was only partly reversed. These studies demonstrate that diabetic nephropathy can be reversed by a relatively simple dietary intervention. Whether reduced glucose metabolism mediates the protective effects of the ketogenic diet remains to be determined. PMID:21533091
-
3 CFR - Continuation of the National Emergency With Respect to the Western Balkans
Code of Federal Regulations, 2010 CFR
2010-01-01
... 3 The President 1 2010-01-01 2010-01-01 false Continuation of the National Emergency With Respect to the Western Balkans Presidential Documents Other Presidential Documents Notice of June 22, 2009 Continuation of the National Emergency With Respect to the Western Balkans On June 26, 2001, by Executive Order 13219, the President declared a...
-
3 CFR - Continuation of the National Emergency With Respect to the Western Balkans
Code of Federal Regulations, 2014 CFR
2014-01-01
... 3 The President 1 2014-01-01 2014-01-01 false Continuation of the National Emergency With Respect to the Western Balkans Presidential Documents Other Presidential Documents Notice of June 17, 2013 Continuation of the National Emergency With Respect to the Western Balkans On June 26, 2001, by Executive Order 13219, the President declared a...
-
3 CFR - Continuation of the National Emergency With Respect to the Western Balkans
Code of Federal Regulations, 2012 CFR
2012-01-01
... 3 The President 1 2012-01-01 2012-01-01 false Continuation of the National Emergency With Respect to the Western Balkans Presidential Documents Other Presidential Documents Notice of June 23, 2011 Continuation of the National Emergency With Respect to the Western Balkans On June 26, 2001, by Executive Order 13219, the President declared a...
-
Pathogenesis of diabetic nephropathy.
Raptis, A E; Viberti, G
2001-01-01
Diabetic Nephropathy (DN) is the commonest cause of end-stage renal failure (ESRF) in the Western world. Diabetic nephropathy follows a well outline clinical course, starting with microalbuminuria through proteinuria, azotaemia and culminating in ESRF. Before the onset of overt proteinuria, there are various renal functional changes including renal hyperfiltration, hyperperfusion, and increasing capillary permeability to macromolecules. Basement-membrane thickening and mesangial expansion have long been recognized as pathological hallmark of diabetes. It has been postulated that DN occurs as a result of the interplay of metabolic and hemodynamic factors in the renal microcirculation. There is no doubt that there is a positive relationship between hyperglycaemia, which is necessary but not sufficient, and microvascular complications. The accumulation of advanced glycosylated end-products (AGEs), the activation of isoform(s) of protein kinase C (PKC) and the acceleration of the aldose reductase pathway may explain how hyperglycemia damages tissue. PKC is one of the key signaling molecules in the induction of the vascular pathology of diabetes. The balance between extracellular matrix production and degradation is important in this context. Transforming growth factor-beta (TGF-beta) appears to play a pivotal role in accumulation in the diabetic kidney. Hemodynamic disturbances are believed to be directly responsible for the development of glomerulosclerosis and its attendant proteinuria. There is familial clustering of diabetic kidney disease. A number of gene loci have been investigated to try to explain the genetic susceptibility to diabetic nephropathy. The genes coding for components of renin-angiotensin system have drawn special attention, due to the central role that this system plays in the regulation of blood pressure, sodium metabolism, and renal hemodynamics. Endothelial dysfunction is closely associated with the development of diabetic retinopathy
-
Incipient and overt diabetic nephropathy in African Americans with NIDDM.
Dasmahapatra, A; Bale, A; Raghuwanshi, M P; Reddi, A; Byrne, W; Suarez, S; Nash, F; Varagiannis, E; Skurnick, J H
1994-04-01
OBJECTIVE--To determine the prevalence of incipient and overt nephropathy in African-American subjects with non-insulin-dependent diabetes mellitus (NIDDM) attending a hospital clinic. Contributory factors, such as blood pressure (BP), duration and age at onset of diabetes, hyperglycemia, hyperlipidemia, and body mass index (BMI) also were evaluated. RESEARCH DESIGN AND METHODS--We recruited 116 African-American subjects with NIDDM for this cross-sectional, descriptive, and analytical study. BP, BMI, 24-h urine albumin excretion, creatinine clearance, serum creatinine, lipids, and GHb levels were measured. Albumin excretion rate (AER) was calculated, and subjects were divided into three groups: no nephropathy (AER < 20 micrograms/min), incipient nephropathy (AER 20-200 micrograms/min), and overt nephropathy (AER > 200 micrograms/min). Frequency of hypertension and nephropathy was analyzed by chi 2 testing, group means were compared using analysis of variance, and linear correlations were performed between AER and other variables. Multiple regression analysis was used to examine the association of these variables while controlling for the effects of other variables. RESULTS--Increased AER was present in 50% of our subjects; 31% had incipient and 19% had overt nephropathy. Hypertension was present in 72.4%; nephropathy, particularly overt nephropathy, was significantly more prevalent in the hypertensive group. Mean BP and diastolic blood pressure (dBP) were higher in the groups with incipient and overt nephropathy, and systolic blood pressure (sBP) was increased in overt nephropathy. Men with either form of nephropathy had higher sBP, dBP, and mean BP, whereas only women with overt nephropathy had increased sBP and mean BP. Subjects with incipient or overt nephropathy had a longer duration of diabetes, and those with overt nephropathy had a younger age at onset of diabetes. By multiple regression analysis, AER correlated with younger age at diabetes onset, but not
-
Sarcopenia in diabetic nephropathy: a cross-sectional study.
Çeliker, Meral; Selçuk, Mustafa Yavuz; Olt, Serdar
2018-06-01
To investigate the relationship between sarcopenia and diabetic nephropathy. 56 diabetic patients without complications, 50 diabetic patients with nephropathy, 53 healthy controls included in this present study. Demographic characteristics such as sex, age, anthropometric measurements such as weight, body mass index [BMI], hip circumference, waist circumference and upper arm circumference were measured. Sarcopenia diagnosis was based on European Working Group on Sarcopenia in Older People [EWGSOP] criteria which consist of hand grip strength, 6-meter walking test and muscle mass. The frequency of sarcopenia increased gradually from 15.1% in healthy control group to 21.4% in the diabetes group, and 34% in diabetic nephropathy group (X2 for trend, p = 0.029). The frequency of sarcopenia was similar in diabetes and diabetic nephropathy group. However, the frequency of sarcopenia was higher in diabetic nephropathy than healthy controls (OR = 2.89, CI [1.11-7.51] in logistic regression). In the present study, the prevalence of sarcopenia was higher in patients with diabetic nephropathy compared to healthy controls.
-
Update on Diabetic Nephropathy: Core Curriculum 2018.
Umanath, Kausik; Lewis, Julia B
2018-06-01
Diabetic kidney disease and diabetic nephropathy are the leading cause of end-stage kidney disease in the United States and most developed countries. Diabetes accounts for 30% to 50% of the incident cases of end-stage kidney disease in the United States. Although this represents a significant public health concern, it is important to note that only 30% to 40% of patients with diabetes develop diabetic nephropathy. Specific treatment of patients with diabetic nephropathy can be divided into 4 major arenas: cardiovascular risk reduction, glycemic control, blood pressure control, and inhibition of the renin-angiotensin system (RAS). Recommendations for therapy include targeting a hemoglobin A 1c concentration < 7% and blood pressure < 140/90mmHg with therapy anchored around the use of a RAS-blocking agent. The single best evidence-based therapy for diabetic nephropathy is therapy with a RAS-blocking medication. This Core Curriculum outlines and discusses in detail the epidemiology, pathophysiology, diagnosis, and management of diabetic nephropathy. Copyright © 2017 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
-
Meta-analysis of depleted uranium levels in the Balkan region.
Besic, Larisa; Muhovic, Imer; Asic, Adna; Kurtovic-Kozaric, Amina
2017-06-01
In recent years, contradicting data has been published on the connection between the presence of depleted uranium and an increased cancer incidence among military personnel deployed in the Balkans during the 1992-1999 wars. This has led to numerous research articles investigating possible depleted uranium contamination of the afflicted regions of the Balkan Peninsula, namely Bosnia & Herzegovina, Serbia, Kosovo and Montenegro. The aim of this study was to collect data from previously published reports investigating the levels of depleted uranium in the Balkans and to present the data in the form of a meta-analysis. This would provide a clear image of the extent of depleted uranium contamination after the Balkan conflict. In addition, we tested the hypothesis that there is a correlation between the levels of depleted uranium and the assumed depleted uranium-related health effects. Our results suggest that the majority of the examined sites contain natural uranium, while the area of Kosovo appears to be most heavily afflicted by depleted uranium pollution, followed by Bosnia & Herzegovina. Furthermore, the results indicate that it is not possible to make a valid correlation between the health effects and depleted uranium-contaminated areas. We therefore suggest a structured collaborative plan of action where long-term monitoring of the residents of depleted uranium-afflicted areas would be performed. In conclusion, while the possibility of depleted uranium toxicity in post-conflict regions appears to exist, there currently exists no definitive proof of such effects, due to insufficient studies of potentially afflicted populations, in addition to the lack of a common epidemiological approach in the reviewed literature. Copyright © 2017 Elsevier Ltd. All rights reserved.
-
Kirilova, Savina; Skoric, Lea
2016-09-01
This is the 19th in a series of articles exploring international trends in health science librarianship in the 21st century. The focus of the present issue is the Balkan Region (Bulgaria and Croatia). The next regular feature column will investigate two other Balkan states - Serbia and Slovenia. JM. © 2016 Health Libraries Group.
-
Rodent models of diabetic nephropathy: their utility and limitations
Kitada, Munehiro; Ogura, Yoshio; Koya, Daisuke
2016-01-01
Diabetic nephropathy is the most common cause of end-stage renal disease. Therefore, novel therapies for the suppression of diabetic nephropathy must be developed. Rodent models are useful for elucidating the pathogenesis of diseases and testing novel therapies, and many type 1 and type 2 diabetic rodent models have been established for the study of diabetes and diabetic complications. Streptozotocin (STZ)-induced diabetic animals are widely used as a model of type 1 diabetes. Akita diabetic mice that have an Ins2+/C96Y mutation and OVE26 mice that overexpress calmodulin in pancreatic β-cells serve as a genetic model of type 1 diabetes. In addition, db/db mice, KK-Ay mice, Zucker diabetic fatty rats, Wistar fatty rats, Otsuka Long-Evans Tokushima Fatty rats and Goto-Kakizaki rats serve as rodent models of type 2 diabetes. An animal model of diabetic nephropathy should exhibit progressive albuminuria and a decrease in renal function, as well as the characteristic histological changes in the glomeruli and the tubulointerstitial lesions that are observed in cases of human diabetic nephropathy. A rodent model that strongly exhibits all these features of human diabetic nephropathy has not yet been developed. However, the currently available rodent models of diabetes can be useful in the study of diabetic nephropathy by increasing our understanding of the features of each diabetic rodent model. Furthermore, the genetic background and strain of each mouse model result in differences in susceptibility to diabetic nephropathy with albuminuria and the development of glomerular and tubulointerstitial lesions. Therefore, the validation of an animal model reproducing human diabetic nephropathy will significantly facilitate our understanding of the underlying genetic mechanisms that contribute to the development of diabetic nephropathy. In this review, we focus on rodent models of diabetes and discuss the utility and limitations of these models for the study of diabetic
-
Cholemic nephropathy - Historical notes and novel perspectives.
Krones, Elisabeth; Pollheimer, Marion J; Rosenkranz, Alexander R; Fickert, Peter
2018-04-01
Acute kidney injury is common in patients with liver disease and associated with significant morbidity and mortality. Besides bacterial infections, fluid loss, and use of nephrotoxic drugs AKI in liver disease may be triggered by tubular toxicity of cholephiles. Cholemic nephropathy, also known as bile cast nephropathy, supposedly represents a widely underestimated but important cause of renal dysfunction in cholestasic or advanced liver diseases with jaundice. Cholemic nephropathy describes impaired renal function along with characteristic histomorphological changes consisting of intratubular cast formation and tubular epithelial cell injury directed towards distal nephron segments. The underlying pathophysiologic mechanisms are not entirely understood and clear defined diagnostic criteria are still missing. This review aims to summarize (i) the present knowledge on clinical and morphological characteristics of cholemic nephropathy, (ii) available preclinical models, (iii) potential pathomechanisms especially the potential role of bile acids, and (iv) future diagnostic and therapeutic strategies for cholemic nephropathy. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen. Copyright © 2017 Elsevier B.V. All rights reserved.
-
New insights on the seismic hazard in the Balkans inferred from GPS
NASA Astrophysics Data System (ADS)
D'Agostino, Nicola; Métois, Marianne; Avallone, Antonio; Chamot-Rooke, Nicolas
2014-05-01
The Balkans region sits at the transition between stable Eurasia and highly straining continental Eastern Mediterranean, resulting in a widespread seismicity and high seismic hazard. Because of intensive human and economic development over the last decades, the vulnerability has increased in the region faster than the progress in seismic hazard assessments. Opposite to the relatively good understanding of the seismicity in plate boundaries contexts, the seismic hazard is poorly known in the regions of distributed continental deformation like the Balkan region and is often underestimated (England and Jackson, 2011). Current seismic hazard assessments are based on the historical and instrumental catalogues. However, the completeness interval of the historical data bases may be below the average recurrence of individual seismogenic structures. In addition, relatively sparse seismological networks in the region and limited cross-border seismic data exchanges cast doubts in seismotectonic interpretation and challenge our understanding of seismic and geodynamic processes. This results in a inhomogeneous knowledge of the seismic hazard of the region to date. Geodetic measurements have the capability to contribute to seismic hazard by mapping the field of current active deformation and translating it into estimates of the seismogenic potential. With simple assumptions, measurements of crustal deformation can be translated in estimates of the average frequency and magnitude of the largest events and assessments of the aseismic deformation. GPS networks in the Balkans have been growing during the last few years mainly for civilian application (e.g. Cadastral plan, telecommunications), but opening new opportunities to quantify the present-day rates of crustal deformation. Here we present the initial results of GEOSAB (Geodetic Estimate of Strain Accumulation over Balkans), an AXA-Research-Fund supported project devoted to the estimation of crustal deformation and the
-
Post Second World War immigration from Balkan countries to Turkey.
Kirisci, K
1995-01-01
"Although there are some works, both in English and Turkish, that have studied migration into the Ottoman empire from the Balkans during the 19th century...it is difficult to find any systematic and comprehensive literature that examines the period since the establishment of the Turkish Republic.... This article aims at filling some of this gap....[The article offers] an analysis of the size and causes of migration from the Balkans to Turkey since the end of the Second World War. The statistics for tables used in this article, unless stated otherwise, have been obtained from the General Directorate of Village Works in Ankara, which is responsible for keeping the statistical records on immigrants arriving in Turkey." excerpt
-
Kovacevic, Lejla; Tambets, Kristiina; Ilumäe, Anne-Mai; Kushniarevich, Alena; Yunusbayev, Bayazit; Solnik, Anu; Bego, Tamer; Primorac, Dragan; Skaro, Vedrana; Leskovac, Andreja; Jakovski, Zlatko; Drobnic, Katja; Tolk, Helle-Viivi; Kovacevic, Sandra; Rudan, Pavao; Metspalu, Ene; Marjanovic, Damir
2014-01-01
Contemporary inhabitants of the Balkan Peninsula belong to several ethnic groups of diverse cultural background. In this study, three ethnic groups from Bosnia and Herzegovina - Bosniacs, Bosnian Croats and Bosnian Serbs - as well as the populations of Serbians, Croatians, Macedonians from the former Yugoslav Republic of Macedonia, Montenegrins and Kosovars have been characterized for the genetic variation of 660 000 genome-wide autosomal single nucleotide polymorphisms and for haploid markers. New autosomal data of the 70 individuals together with previously published data of 20 individuals from the populations of the Western Balkan region in a context of 695 samples of global range have been analysed. Comparison of the variation data of autosomal and haploid lineages of the studied Western Balkan populations reveals a concordance of the data in both sets and the genetic uniformity of the studied populations, especially of Western South-Slavic speakers. The genetic variation of Western Balkan populations reveals the continuity between the Middle East and Europe via the Balkan region and supports the scenario that one of the major routes of ancient gene flows and admixture went through the Balkan Peninsula. PMID:25148043
-
Kovacevic, Lejla; Tambets, Kristiina; Ilumäe, Anne-Mai; Kushniarevich, Alena; Yunusbayev, Bayazit; Solnik, Anu; Bego, Tamer; Primorac, Dragan; Skaro, Vedrana; Leskovac, Andreja; Jakovski, Zlatko; Drobnic, Katja; Tolk, Helle-Viivi; Kovacevic, Sandra; Rudan, Pavao; Metspalu, Ene; Marjanovic, Damir
2014-01-01
Contemporary inhabitants of the Balkan Peninsula belong to several ethnic groups of diverse cultural background. In this study, three ethnic groups from Bosnia and Herzegovina - Bosniacs, Bosnian Croats and Bosnian Serbs - as well as the populations of Serbians, Croatians, Macedonians from the former Yugoslav Republic of Macedonia, Montenegrins and Kosovars have been characterized for the genetic variation of 660 000 genome-wide autosomal single nucleotide polymorphisms and for haploid markers. New autosomal data of the 70 individuals together with previously published data of 20 individuals from the populations of the Western Balkan region in a context of 695 samples of global range have been analysed. Comparison of the variation data of autosomal and haploid lineages of the studied Western Balkan populations reveals a concordance of the data in both sets and the genetic uniformity of the studied populations, especially of Western South-Slavic speakers. The genetic variation of Western Balkan populations reveals the continuity between the Middle East and Europe via the Balkan region and supports the scenario that one of the major routes of ancient gene flows and admixture went through the Balkan Peninsula.
-
Autophagy: A Novel Therapeutic Target for Diabetic Nephropathy.
Kume, Shinji; Koya, Daisuke
2015-12-01
Diabetic nephropathy is a leading cause of end stage renal disease and its occurance is increasing worldwide. The most effective treatment strategy for the condition is intensive treatment to strictly control glycemia and blood pressure using renin-angiotensin system inhibitors. However, a fraction of patients still go on to reach end stage renal disease even under such intensive care. New therapeutic targets for diabetic nephropathy are, therefore, urgently needed. Autophagy is a major catabolic pathway by which mammalian cells degrade macromolecules and organelles to maintain intracellular homeostasis. The accumulation of damaged proteins and organelles is associated with the pathogenesis of diabetic nephropathy. Autophagy in the kidney is activated under some stress conditions, such as oxidative stress and hypoxia in proximal tubular cells, and occurs even under normal conditions in podocytes. These and other accumulating findings have led to a hypothesis that autophagy is involved in the pathogenesis of diabetic nephropathy. Here, we review recent findings underpinning this hypothesis and discuss the advantages of targeting autophagy for the treatment of diabetic nephropathy.
-
Preventive Effect of Salicylate and Pyridoxamine on Diabetic Nephropathy
Abouzed, Tarek Kamal; Munesue, Seiichi; Harashima, Ai; Masuo, Yusuke; Kato, Yukio; Khailo, Khaled; Yamamoto, Hiroshi
2016-01-01
Objective. Diabetic nephropathy is a life-threatening complication in patients with long-standing diabetes. Hemodynamic, inflammatory, and metabolic factors are considered as developmental factors for diabetic nephropathy. In this study, we evaluated whether pharmacological interventions with salicylate, compared to pyridoxamine, could prevent diabetic nephropathy in mice. Methods. Male mice overexpressing inducible nitric oxide synthase in pancreatic β-cells were employed as a diabetic model. Salicylate (3 g/kg diet) or pyridoxamine (1 g/L drinking water; ~200 mg/kg/day) was given for 16 weeks to assess the development of diabetic nephropathy. Treatment with long-acting insulin (Levemir 2 units/kg twice a day) was used as a control. Results. Although higher blood glucose levels were not significantly affected by pyridoxamine, early to late stage indices of nephropathy were attenuated, including kidney enlargement, albuminuria, and increased serum creatinine, glomerulosclerosis, and inflammatory and profibrotic gene expressions. Salicylate showed beneficial effects on diabetic nephropathy similar to those of pyridoxamine, which include lowering blood glucose levels and inhibiting macrophage infiltration into the kidneys. Attenuation of macrophage infiltration into the kidneys and upregulation of antiglycating enzyme glyoxalase 1 gene expression were found only in the salicylate treatment group. Conclusions. Treatment with salicylate and pyridoxamine could prevent the development of diabetic nephropathy in mice and, therefore, would be a potentially useful therapeutic strategy against kidney problems in patients with diabetes. PMID:28042580
-
The Family Investigation of Nephropathy and Diabetes (FIND): design and methods.
Knowler, William C; Coresh, Josef; Elston, Robert C; Freedman, Barry I; Iyengar, Sudha K; Kimmel, Paul L; Olson, Jane M; Plaetke, Rosemarie; Sedor, John R; Seldin, Michael F
2005-01-01
The Family Investigation of Nephropathy and Diabetes (FIND) is a multicenter study designed to identify genetic determinants of diabetic nephropathy. It is conducted in eight U.S. clinical centers and a coordinating center, and with four ethnic groups (European Americans, African Americans, Mexican Americans, and American Indians). Two strategies are used to localize susceptibility genes: a family-based linkage study and a case-control study using mapping by admixture linkage disequilibrium (MALD). In the family-based study, probands with diabetic nephropathy are recruited with their parents and selected siblings. Linkage analyses will be conducted to identify chromosomal regions containing genes that influence the development of diabetic nephropathy or related quantitative traits such as serum creatinine concentration, urinary albumin excretion, and plasma glucose concentrations. Regions showing evidence of linkage will be examined further with both genetic linkage and association studies to identify genes that influence diabetic nephropathy or related traits. Two types of MALD studies are being done. One is a case-control study of unrelated individuals of Mexican American heritage in which both cases and controls have diabetes, but only the case has nephropathy. The other is a case-control study of African American patients with nephropathy (cases) and their spouses (controls) unaffected by diabetes and nephropathy; offspring are genotyped when available to provide haplotype data. Identification of genes that influence susceptibility to diabetic nephropathy will lead to a better understanding of how nephropathy develops. This should eventually lead to improved treatment and prevention.
-
Pirfenidone for Diabetic Nephropathy
Ix, Joachim H.; Mathew, Anna V.; Cho, Monique; Pflueger, Axel; Dunn, Stephen R.; Francos, Barbara; Sharma, Shoba; Falkner, Bonita; McGowan, Tracy A.; Donohue, Michael; RamachandraRao, Satish; Xu, Ronghui; Fervenza, Fernando C.; Kopp, Jeffrey B.
2011-01-01
Pirfenidone is an oral antifibrotic agent that benefits diabetic nephropathy in animal models, but whether it is effective for human diabetic nephropathy is unknown. We conducted a randomized, double-blind, placebo-controlled study in 77 subjects with diabetic nephropathy who had elevated albuminuria and reduced estimated GFR (eGFR) (20 to 75 ml/min per 1.73 m2). The prespecified primary outcome was a change in eGFR after 1 year of therapy. We randomly assigned 26 subjects to placebo, 26 to pirfenidone at 1200 mg/d, and 25 to pirfenidone at 2400 mg/d. Among the 52 subjects who completed the study, the mean eGFR increased in the pirfenidone 1200-mg/d group (+3.3 ± 8.5 ml/min per 1.73 m2) whereas the mean eGFR decreased in the placebo group (−2.2 ± 4.8 ml/min per 1.73 m2; P = 0.026 versus pirfenidone at 1200 mg/d). The dropout rate was high (11 of 25) in the pirfenidone 2400-mg/d group, and the change in eGFR was not significantly different from placebo (−1.9 ± 6.7 ml/min per 1.73 m2). Of the 77 subjects, 4 initiated hemodialysis in the placebo group, 1 in the pirfenidone 2400-mg/d group, and none in the pirfenidone 1200-mg/d group during the study (P = 0.25). Baseline levels of plasma biomarkers of inflammation and fibrosis significantly correlated with baseline eGFR but did not predict response to therapy. In conclusion, these results suggest that pirfenidone is a promising agent for individuals with overt diabetic nephropathy. PMID:21511828
-
Antiphospholipid Syndrome Nephropathy: From Pathogenesis to Treatment.
Tektonidou, Maria G
2018-01-01
Kidney damage is a well-recognized complication of the antiphospholipid syndrome (APS), either primary or systemic lupus erythematosus (SLE)-associated APS. Kidney involvement in APS involves a variety of manifestations, such as renal artery thrombosis or stenosis, renal vein thrombosis, allograft loss due to thrombosis after kidney transplantation, and injury to the renal microvasculature, also known as APS nephropathy. Biopsy in patients with APS nephropathy includes acute thrombotic microangiopathy lesions and chronic intrarenal vascular lesions such as interlobular fibrous intimal hyperplasia, arterial and arteriolar recanalizing thrombosis, fibrous arterial occlusion, and focal cortical atrophy. The most frequent clinical features are hypertension, microscopic hematuria, proteinuria (ranging from mild to nephritic levels), and renal insufficiency. It is uncertain whether antiphospholipid antibodies or other factors are implicated in the development of APS nephropathy, and whether it is driven mainly by thrombotic or by inflammatory processes. Experimental models and clinical studies of thrombotic microangiopathy lesions implicate activation of the complement cascade, tissue factor, and the mTORC pathway. Currently, the management of APS nephropathy relies on expert opinion, and consensus is lacking. There is limited evidence about the effect of anticoagulants, and their use remains controversial. Treatment approaches in patients with APS nephropathy lesions may include the use of heparin based on its role on complement activation pathway inhibition or the use of intravenous immunoglobulin and/or plasma exchange. Targeted therapies may also be considered based on potential APS nephropathy pathogenetic mechanisms such as B-cell directed therapies, complement inhibition, tissue factor inhibition, mTOR pathway inhibition, or anti-interferon antibodies, but prospective multicenter studies are needed to address their role.
-
Mamos, Tomasz; Bącela-Spychalska, Karolina; Rewicz, Tomasz; Wattier, Remi A.
2017-01-01
Background The Balkans are a major worldwide biodiversity and endemism hotspot. Among the freshwater biota, amphipods are known for their high cryptic diversity. However, little is known about the temporal and paleogeographic aspects of their evolutionary history. We used paleogeography as a framework for understanding the onset of diversification in Gammarus roeselii: (1) we hypothesised that, given the high number of isolated waterbodies in the Balkans, the species is characterised by high level of cryptic diversity, even on a local scale; (2) the long geological history of the region might promote pre-Pleistocene divergence between lineages; (3) given that G. roeselii thrives both in lakes and rivers, its evolutionary history could be linked to the Balkan Neogene paleolake system; (4) we inspected whether the Pleistocene decline of hydrological networks could have any impact on the diversification of G. roeselii. Material and Methods DNA was extracted from 177 individuals collected from 26 sites all over Balkans. All individuals were amplified for ca. 650 bp long fragment of the mtDNA cytochrome oxidase subunit I (COI). After defining molecular operational taxonomic units (MOTU) based on COI, 50 individuals were amplified for ca. 900 bp long fragment of the nuclear 28S rDNA. Molecular diversity, divergence, differentiation and historical demography based on COI sequences were estimated for each MOTU. The relative frequency, geographic distribution and molecular divergence between COI haplotypes were presented as a median-joining network. COI was used also to reconstruct time-calibrated phylogeny with Bayesian inference. Probabilities of ancestors’ occurrence in riverine or lacustrine habitats, as well their possible geographic locations, were estimated with the Bayesian method. A Neighbour Joining tree was constructed to illustrate the phylogenetic relationships between 28S rDNA haplotypes. Results We revealed that G. roeselii includes at least 13 cryptic
-
Lipid Abnormalities in Type 2 Diabetes Mellitus Patients with Overt Nephropathy
Viswanathan, Vijay
2017-01-01
Background Diabetic nephropathy is a major complication of diabetes and an established risk factor for cardiovascular events. Lipid abnormalities occur in patients with diabetic nephropathy, which further increase their risk for cardiovascular events. We compared the degree of dyslipidemia among type 2 diabetes mellitus (T2DM) subjects with and without nephropathy and analyzed the factors associated with nephropathy among them. Methods In this retrospective study, T2DM patients with overt nephropathy were enrolled in the study group (n=89) and without nephropathy were enrolled in the control group (n=92). Both groups were matched for age and duration of diabetes. Data on total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), urea and creatinine were collected from the case sheets. TG/HDL-C ratio, a surrogate marker for small, dense, LDL particles (sdLDL) and estimated glomerular filtration rate (eGFR) were calculated using equations. Multivariate analysis was done to determine the factors associated with eGFR. Results Dyslipidemia was present among 56.52% of control subjects and 75.28% of nephropathy subjects (P=0.012). The percentage of subjects with atherogenic dyslipidemia (high TG+low HDL-C+sdLDL) was 14.13 among controls and 14.61 among nephropathy subjects. Though serum creatinine was not significantly different, mean eGFR value was significantly lower among nephropathy patients (P=0.002). Upon multivariate analysis, it was found that TC (P=0.007) and HDL-C (P=0.06) were associated with eGFR among our study subjects. Conclusion Our results show that dyslipidemia was highly prevalent among subjects with nephropathy. Regular screening for dyslipidemia may be beneficial in controlling the risk for adverse events among diabetic nephropathy patients. PMID:28447439
-
Native Dreissena freshwater mussels in the Balkans: in and out of ancient lakes
NASA Astrophysics Data System (ADS)
Wilke, T.; Schultheiß, R.; Albrecht, C.; Bornmann, N.; Trajanovski, S.; Kevrekidis, T.
2010-10-01
The Balkans is a biogeographically highly diverse region and a worldwide hotspot of endemic freshwater diversity. A substantial part of this diversity is attributed to well recognized and potential ancient lakes in its southwestern part. However, despite considerable research efforts, faunal relationships among those lakes are not well understood. Therefore, genetic information from native representatives of the mussel genus Dreissena is here used to test the biogeographical zonation of the southwestern Balkans, to relate demographic changes to environmental changes, to assess the degree of eco-insularity, to reconstruct their evolutionary history, and to explore the potential of native taxa for becoming invasive. Phylogeographical and population genetic analyses indicate that most studied populations belong to two native species: D. presbensis (including the distinct genetic subgroup from Lake Ohrid, "D. stankovici") and D. blanci. In addition, the first confirmed record of invasive D. polymorpha in the southwestern Balkan is presented. The distribution of native Dreissena spp. generally coincides with the biogeographical zonations previously suggested based on fish data. However, there is disagreement on the assignment of the ancient lakes in the area to respective biogeographical regions. The data for Lake Ohrid are not conclusive. A closer biogeographical connection to lakes of the Vardar region and possibly the northern Ionian region is, however, suggested for Lake Prespa. The reconstruction of the evolutionary history of Dreissena spp. suggests that populations underwent demographic and spatial expansions in the recent past. Expansions started around 320 000-300 000 years ago in "D. stankovici", 160 000-140 000 years ago in D. blanci, and 110 000-70 000 years ago in D. presbensis. These time frames are discussed within the context of available paleogeological data for lakes Ohrid and Prespa. It is suggested that regional environmental changes may have had
-
Cultural Identity and Regional Security in the Western Balkans
2013-06-13
possible. Case Study as Qualitative Approach Creswell and other experts of the social research methodology suggest at least five forms of...descriptive research approach, and the main method is case study of the Western Balkans. This thesis utilizes the analytical frameworks of securitization
-
Protease activated receptor 2 in diabetic nephropathy: a double edged sword
Waasdorp, Maaike; Duitman, JanWillem; Florquin, Sandrine; Spek, Arnold C
2017-01-01
Diabetic nephropathy is a major microvascular complication of diabetes mellitus, and the leading cause of end stage renal disease worldwide. The pathogenesis of diabetic nephropathy is complex, making the development of novel treatments that stop or reverse the progression of microalbuminuria into end stage renal disease a challenge. Protease activated receptor (PAR)-2 has recently been shown to aggravate disease progression in diabetic nephropathy based upon which it was suggested that PAR-2 would be a potential target for the treatment of diabetic nephropathy. To fully appreciate the translational potential of PAR-2 in diabetic nephropathy, we evaluated the effect of PAR-2 deficiency on the development of diabetic nephropathy in a streptozotocin-induced diabetes model characteristic of type 1 diabetes. Although diabetic PAR-2 deficient mice showed reduced albuminuria compared to diabetic wild type mice, an increase in mesangial expansion was evident in the PAR-2 deficient mice. No differences were observed in blood glucose levels, podocyte numbers or in glomerular vascular density. These results show that PAR-2 plays a dual role in the development of streptozotocin-induced diabetic nephropathy and may thus not be the eagerly awaited novel target to combat diabetic nephropathy. Targeting PAR-2 should consequently only be pursued with great care in a clinical setting. PMID:29118913
-
Gurinović, Mirjana; Milešević, Jelena; Novaković, Romana; Kadvan, Agnes; Djekić-Ivanković, Marija; Šatalić, Zvonimir; Korošec, Mojca; Spiroski, Igor; Ranić, Marija; Dupouy, Eleonora; Oshaug, Arne; Finglas, Paul; Glibetić, Maria
2016-02-15
The objective of this paper is to share experience and provide updated information on Capacity Development in the Central and Eastern Europe/Balkan Countries (CEE/BC) region relevant to public health nutrition, particularly in creation of food composition databases (FCDBs), applying dietary intake assessment and monitoring tools, and harmonizing methodology for nutrition surveillance. Balkan Food Platform was established by a Memorandum of Understanding among EuroFIR AISBL, Institute for Medical Research, Belgrade, Capacity Development Network in Nutrition in CEE - CAPNUTRA and institutions from nine countries in the region. Inventory on FCDB status identified lack of harmonized and standardized research tools. To strengthen harmonization in CEE/BC in line with European research trends, the Network members collaborated in development of a Regional FCDB, using web-based food composition data base management software following EuroFIR standards. Comprehensive nutrition assessment and planning tool - DIET ASSESS & PLAN could enable synchronization of nutrition surveillance across countries. Copyright © 2015 Elsevier Ltd. All rights reserved.
-
Papillary Necrosis in Experimental Analgesic Nephropathy
Saker, B. M.; Kincaid-Smith, Priscilla
1969-01-01
A proprietary aspirin, phenacetin, and caffeine preparation given to rats in a dose equivalent to that taken by patients with analgesic nephropathy produced papillary necrosis in 55%. There was a higher incidence in rats deprived of fluids overnight. Papillary necrosis was not noted in rats receiving twice as much phenacetin. These findings support the argument that phenacetin should not be singled out as the substance responsible for analgesic nephropathy in man. PMID:5762278
-
Ochratoxin A and human health risk: a review of the evidence.
Bui-Klimke, Travis R; Wu, Felicia
2015-01-01
Ochratoxin A (OTA) is a mycotoxin produced by several fungal species including Aspergillus ochraceus, A. carbonarius, A. niger, and Penicillium verrucosum. OTA causes nephrotoxicity and renal tumors in a variety of animal species; however, human health effects are less well-characterized. Various studies have linked OTA exposure with the human diseases Balkan endemic nephropathy (BEN) and chronic interstitial nephropathy (CIN), as well as other renal diseases. This study reviews the epidemiological literature on OTA exposure and adverse health effects in different populations worldwide, and assesses the potential human health risks of OTA exposure. Epidemiological studies identified in a systematic review were used to calculate unadjusted odds ratios for OTA associated with various health endpoints. With one exception, there appears to be no statistically significant evidence for human health risks associated with OTA exposure. One Egyptian study showed a significantly higher risk of nephritic syndrome in those with very high urinary OTA levels compared with relatively unexposed individuals; however, other potential risk factors were not controlled for in the study. Larger cohort or case-control studies are needed in the future to better establish potential OTA-related human health effects, and further duplicate-diet studies are needed to validate biomarkers of OTA exposure in humans.
-
Grave's disease associated with immunoglobulin A nephropathy: A rare association.
Khan, I; Bhat, R A; Khan, I; Hameed, I
2015-01-01
Immunoglobulin A (Ig A) nephropathy is the most common form of primary glomerulonephritis. The association of Ig A nephropathy with Grave's disease has not been reported so far. We report a case of 20-year-old female with Grave's disease who presented with edema, facial puffiness, and decreased urine output. She was found to be hypertensive with renal failure and nephrotic range proteinuria. Renal biopsy revealed features of Ig A nephropathy. The patient was treated with oral corticosteroids (1 mg/kg/day). To our knowledge, this is the first case showing association of Grave's disease with Ig A nephropathy.
-
Grave's disease associated with immunoglobulin A nephropathy: A rare association
Khan, I.; Bhat, R. A.; Khan, I.; Hameed, I.
2015-01-01
Immunoglobulin A (Ig A) nephropathy is the most common form of primary glomerulonephritis. The association of Ig A nephropathy with Grave's disease has not been reported so far. We report a case of 20-year-old female with Grave's disease who presented with edema, facial puffiness, and decreased urine output. She was found to be hypertensive with renal failure and nephrotic range proteinuria. Renal biopsy revealed features of Ig A nephropathy. The patient was treated with oral corticosteroids (1 mg/kg/day). To our knowledge, this is the first case showing association of Grave's disease with Ig A nephropathy. PMID:26199479
-
[Membranous nephropathy: Pathophysiology and natural history].
Seitz-Polski, Barbara; Lambeau, Gérard; Esnault, Vincent
2017-04-01
Membranous nephropathy is a major cause of nephrotic syndrome in adults, with various etiologies and outcomes. One third of patients enter spontaneous remission with blockade of the renin-angiotensin system, one third develop a persistent nephrotic syndrome, while another third of patients develop end-stage kidney disease and 40% of them relapse after kidney transplantation. Treatment of membranous nephropathy remains controversial. Immunosuppressive therapy is only recommended in case of renal function deterioration or persistent nephrotic syndrome after 6months of renin-angiotensin system blockade. Therefore, delayed immunosuppressive treatments may lead to significant and potentially irreversible complications. For long, no biological markers could predict clinical outcome and guide therapy. The discovery of autoantibodies to the phospholipase A2 receptor (PLA2R1) in 2009, and to the thrombospondin type 1 domain containing 7A (THSD7A) in 2014 in respectively 70 and 5% of patients with membranous nephropathy were major breakthroughs. The passive infusion of human anti-THSD7A antibodies in mouse induces proteinuria and membranous nephropathy. The identification of these antigens has allowed developing diagnostic and prognostic tests. High anti-PLA2R1 titers at time of diagnosis predict a poor renal outcome. Anti-PLA2R1 antibodies can bind at least three different domains of PLA2R1. Epitope spreading with binding of two or three of these antigenic domains is associated with active membranous nephropathy and poor renal survival. These new tools could help us to monitor disease severity and to predict renal prognosis for a better selection of patients that should benefit of early immunosuppressive therapy. Copyright © 2017 Société francophone de néphrologie, dialyse et transplantation. Published by Elsevier Masson SAS. All rights reserved.
-
Distribution of uranium and some selected trace metals in human scalp hair from Balkans.
Zunic, Z S; Tokonami, S; Mishra, S; Arae, H; Kritsananuwat, R; Sahoo, S K
2012-11-01
The possible consequences of the use of depleted uranium (DU) used in Balkan conflicts in 1995 and 1999 for the people and the environment of this reason need attention. The heavy metal content in human hair may serve as a good indicator of dietary, environmental and occupational exposures to the metal compounds. The present work summarises the distribution of uranium and some selected trace metals such as Mn, Ni, Cu, Zn, Sr, Cd and Cs in the scalp hair of inhabitants from Balkans exposed to DU directly and indirectly, i.e. Han Pijesak, Bratoselce and Gornja Stubla areas. Except U and Cs, all other metals were compared with the worldwide reported values of occupationally unexposed persons. Uranium concentrations show a wide variation ranging from 0.9 ± 0.05 to 449 ± 12 µg kg(-1). Although hair samples were collected from Balkan conflict zones, uranium isotopic measurement ((235)U/(238)U) shows a natural origin rather than DU.
-
Folk Calendars in the Balkan Region
NASA Astrophysics Data System (ADS)
Kolev, Dimiter
Folk calendars are a good source for studying the knowledge and rituals of peoples from distant epochs. The turbulent history of the cultures in the Balkan Peninsula leads to a mixture of calendar traditions - different calendar types and naming systems of the calendar units (months and weekdays). Despite the differences, they share a common astronomical basis and the seasonal structure is of fundamental importance (i.e., dividing the year into two economic seasons - warm and cold). The Old Bulgarian 12-year calendar is also mentioned briefly.
-
Stojanovski, Kristefer; Holla, Alaka; Hoxha, Ilir; Howell, Elizabeth; Janevic, Teresa
2017-12-01
The conflict in Kosovo created mass displacement and a fractured health system. Roma, Ashkali, and Balkan Egyptian communities are particularly vulnerable to discrimination and exclusion from institutions. We aimed to examine Roma, Ashkali, and Balkan Egyptian disparities in quantity and quality of antenatal care received. We conducted a cross-sectional study in August 2012 with 603 women aged 15 or older who had given birth in the previous two years. We measured quantity of antenatal care using number of visits and quality of care using antenatal checklists. We used linear regression with interaction terms of displacement and type of health institution (for example, Serbian or Kosovar) to assess ethnic disparities in antenatal care. Women from Roma, Ashkali, and Balkan Egyptian communities received poorer quantity and quality of antenatal care compared to Kosovar Albanian and Serbian women. In adjusted models, Roma, Ashkali, and Balkan Egyptian women scored 3.5 points lower [95% CI (-5.2, -1.8)] on the checklists. Roma, Ashkali, and Balkan Egyptian women who were displaced received even poorer quality of care. Ethnic disparities exist in quality of antenatal care. Women from Roma, Ashkali, and Balkan Egyptian communities receive the poorest quality of services. As Kosovo strives to build a multiethnic health care system, a focus on equity is important to ensure the right to health for Roma, Ashkali, and Balkan Egyptian women.
-
Nationalism and Ethnic Conflict in Southern Balkans
2002-06-01
political rather than a religious struggle 114. The creation of the new church in the period 1870-1890, motivated many Christians to convert to the...had a very unsuccessful foreign policy. In three wars - Second Balkan War 1913, the First World War 1914 - 1918 and the Second World War 1939-1945...that occupied them. For those who refused the conversion expulsion was the price147. After the First World War 1914 - 1918 , the exchange of
-
Glycopatterns of Urinary Protein as New Potential Diagnosis Indicators for Diabetic Nephropathy
Zhu, Hanyu; Liu, Moyan; Zhong, Yaogang; Shu, Jian; Fu, Xinle; Cai, Guangyan; Chen, Xiangmei; Geng, Wenjia; Yang, Xiaoli; Wu, Minghui
2017-01-01
Diabetic nephropathy is a major cause of chronic kidney disease and end-stage kidney disease. However, so little is known about alterations of the glycopatterns in urine with the development of diabetic nephropathy. Presently, we interrogated glycopatterns in urine specimens using a lectin microarray. The results showed that expression levels of Siaα2-6Gal/GalNAc recognized by SNA exhibited significantly increased tendency with the development of diabetic nephropathy; moreover, SNA blotting indicated glycoproteins (90 kDa, 70 kDa, and 40 kDa) in urine may contribute to this alteration. Furthermore, the glycopatterns of (GlcNAc)2–4 recognized by STL exhibited difference between diabetic and nondiabetic nephropathy. The results of urinary protein microarray fabricated by another 48 urine specimens also indicated (GlcNAc)2–4 is a potential indictor to differentiate the patients with diabetic nephropathy from nondiabetic nephropathy. Furtherly, STL blotting showed that the 50 kDa glycoproteins were correlated with this alteration. In conclusion, our data provide pivotal information to monitor the development of diabetic nephropathy and distinguish between diabetic nephropathy and nondiabetic renal disease based on precise alterations of glycopatterns in urinary proteins, but further studies are needed in this regard. PMID:28401167
-
A new GPS velocity field in the south-western Balkans: insights for continental dynamics
NASA Astrophysics Data System (ADS)
D'Agostino, N.; Avallone, A.; Duni, L.; Ganas, A.; Georgiev, I.; Jouanne, F.; Koci, R.; Kuka, N.; Metois, M.
2017-12-01
The Balkans peninsula is an area of active distributed deformation located at the southern boundary of the Eurasian plate. Relatively low strain rates and logistical reasons have so far limited the characterization and definition of the active tectonics and crustal kinematics. The increasing number of GNSS stations belonging to national networks deployed for scientific and cadastral purposes, now provides the opportunity to improve the knowledge of the crustal kinematics in this area and to define a cross-national velocity field that illuminates the active tectonic deformation. In this work we homogeneously processed the data from the south western Balkans and neighbouring regions using available rinex files from scientific and cadastral networks (ALBPOS, EUREF, HemusNET, ITALPOS, KOPOS, MAKPOS, METRICA, NETGEO, RING, TGREF). In order to analyze and interpret station velocities relative to the Eurasia plate and to reduce the common mode signal, we updated the Eurasian terrestrial reference frame described in Métois et al. 2015. Starting from this dataset we present a new GPS velocity field covering the south western part of the Balkan Peninsula. Using this new velocity field, we derive the strain rate tensor to analyze the regional style of the deformation. Our results (1) improve the picture of the general southward flow of the crust characterizing the south western Balkans behind the contractional belt at the boundary with Adriatic and (2) provide new key elements for the understanding of continental dynamics in this part of the Eurasian plate boundary.
-
"Balkan journal of medical genetics"--facts, editorial policies, practices and challenges.
Plaseska Karanfilska, Dijana; Sukarova Stefanovska, Emilija
2014-01-01
The Balkan Journal of Medical Genetics (BJMG) is an international, open access journal that publishes scientific papers covering different aspects of medical genetics. It is published by the Macedonian Academy of Sciences and Arts twice a year in both printed and electronic versions. BJMG is covered by many abstracting and indexing databases, including PubMed Central and Thomson Reuters. Although there are many journals in the field of medical genetics, only a few come from regions outside Western Europe and North America. Being one of these few journals, BJMG aims to promote genetics and research on this topic in the Balkan countries and beyond. BJMG's ultimate goal is to raise the scientific quality and metrics of the journal and provide a better place for BJMG in the community of scientific journals.
-
Medical and Social Aspects of Syphilis in the Balkans from the mid-19th Century to the Interwar.
Tsiamis, Costas; Vrioni, Georgia; Poulakou-Rebelakou, Effie; Gennimata, Vasiliki; Murdjeva, Mariana А; Tsakris, Athanasios
2016-03-01
The current study presents some aspects of syphilis in the Balkan Peninsula from the 19th century until the Interwar. Ever since the birth of modern Balkan States (Greece, Bulgaria, Turkey and Serbia), urbanization, poverty and the frequent wars have been considered the major factors conducive to the spread of syphilis. The measures against sex work and sexually transmitted diseases (STDs) were taken in two aspects, one medical and the other legislative. In this period, numerous hospitals for venereal diseases were established in the Balkan countries. In line with the international diagnostic approach and therapeutic standards, laboratory examinations in these Balkan hospitals included spirochete examination, Wassermann reaction, precipitation reaction and cerebrospinal fluid examination. Despite the strict legislation and the adoption of relevant laws against illegal sex work, public health services were unable to curb the spread of syphilis. Medical and social factors such as poverty, citizen's ignorance of STDs, misguided medical perceptions, lack of sanitary control of prostitution and epidemiological studies, are highlighted in this study. These factors were the major causes that helped syphilis spread in the Balkan countries during the 19th and early 20th century. The value of these aspects as a historic paradigm is diachronic. Failure to comply with the laws and the dysfunction of public services during periods of war or socioeconomic crises are both factors facilitating the spread of STDs.
-
[Pathological features and clinical manifestations in 313 children with nephropathy under 6].
Dang, Xi-qiang; Cao, Yan; Yi, Zhu-wen; Xu, Zi-chuan; He, Xiao-jie; Huang, Dan-lin
2008-03-01
To explore the relationship between pathological features and clinical manifestations in children with nephropathy under 6 years old. Renal biopsy by rapid percutaneous puncturation was performed on 313 children under 6 who were all diagnosed clinically as kidney diseases of 14 different kinds. The specimens were divided into 3 parts for microscope, electron microscope and immuno fluorescence examination respectively and processed by HE, PAS, PASM, and Masson staining. Immunofluorescence was used to detect the deposition of IgG, IgM, IgA, C3, C4, C1q, and Fb in the renal tissues. Additional examinations were done to detect HBs-Ag, HBeAg and HBcAg deposition in some cases with positive serum HBs-Ag. Altogether 290 of the specimens (290/313, 92.65%) were examined by electron microscope. All the renal biopsy performances were successful. The clinical manifestations comprised of persistent haematuria (32.92%, 103/313), idiopathic nephritic syndrome (26.1%, 82/313), acute nephritic syndrome (20.14%, 63/313), Henoch Schonlein purpura nephritis (8.32%, 26/313), HBV-nephritis (4.79%, 15/313), and isolated proteinuria (2.56%, 8/313). The main pathological patterns of glomerular disease were identified as mesangial proliferation (51.75%, 162/313), IgM nephropathy (8.31%,26/313), minor and minimal change (7.99%, 25/313), IgA nephropathy (7.35%, 23/313), endocapillary proliferative glomerulonephritis (5.11%, 16/313), focus segmental glomerulosclerosis (4.47%, 14/313), thin basement membrane nephropathy (4.47%, 14/313), and membrane nephropathy (4.47%, 14/313). Alport syndrome, congenital nephrotic syndrome, and thin basement membrane nephropathy can be diagnosed by electron microscope, white IgA nephropathy, IgM nephropathy and C1q nephropathy by immunopathology. Similar clinical manifestations may differ in the pathology and the clinical features of one pathological diagnosis may vary greatly. Renal biopsy is of great help to the diagnosis, treatment and the prognosis
-
Management of Hypertension in Diabetic Nephropathy: How Low Should We Go?
Sternlicht, Hillel; Bakris, George L
2016-01-01
Hypertension is a frequent comorbidity often following the development of diabetic nephropathy among individuals with type 1 diabetes and affecting most patients with type 2 diabetes at the time of diagnosis. Multiple prospective randomized placebo-controlled trials demonstrate that tight blood pressure control among patients with diabetic nephropathy reduces the rates of macrovascular and microvascular complications. While randomized trials exist and support a blood pressure goal of <140/90 mm Hg for patients with nondiabetic kidney disease, there are no prospective data regarding a specific blood pressure goal on progression of diabetic nephropathy. Retrospective data analyses from trials show a linear relationship between either baseline or achieved study blood pressure and progression of nephropathy. Very high albuminuria is a hallmark of diabetic nephropathy with reductions by either angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blocker (ARB) monotherapy associated with slowed nephropathy progression. However, combination antihypertensive therapy, while decreasing proteinuria, augments the risk of hyperkalemia, hypotension, and kidney dysfunction. Given the lack of trial data for a BP goal among patients with diabetic nephropathy, prospective trials are needed to define the optimal blood pressure necessary to preserve kidney function. At present, guideline blood pressure goals of less than 140/90 mm Hg and the use of ACEi or ARB therapy for those with more than 300 mg of albuminuria are mandated. © 2016 S. Karger AG, Basel.
-
Bunnell, J.E.; Tatu, C.A.; Lerch, H.E.; Orem, W.H.; Pavlovic, N.
2007-01-01
High-molecular-weight organic compounds such as humic acids and/or fulvic acids that are naturally mobilized from lignite beds into untreated drinking-water supplies were suggested as one possible cause of Balkan endemic nephropathy (BEN) and cancer of the renal pelvis. A lab investigation was undertaken in order to assess the nephrotoxic potential of such organic compounds using an in vitro tissue culture model. Because of the infeasibility of exposing kidney tissue to low concentrations of organics for years in the lab, tangential flow ultrafiltration was employed to hyperconcentrate samples suitable for discerning effects in the short time frames necessitated by tissue culture systems. Effects on HK-2 kidney cells were measured using two different cell proliferation assays (MTT and alamarBlue). Results demonstrated that exposure of kidney tissue to high-molecular-weight organics produced excess cell death or proliferation depending on concentration and duration of exposure. Copyright ?? Taylor & Francis Group, LLC.
-
Vitecek, Simon; Kučinić, Mladen; Previšić, Ana; Živić, Ivana; Stojanović, Katarina; Keresztes, Lujza; Bálint, Miklós; Hoppeler, Felicitas; Waringer, Johann; Graf, Wolfram; Pauls, Steffen U
2017-06-06
Taxonomy offers precise species identification and delimitation and thus provides basic information for biological research, e.g. through assessment of species richness. The importance of molecular taxonomy, i.e., the identification and delimitation of taxa based on molecular markers, has increased in the past decade. Recently developed exploratory tools now allow estimating species-level diversity in multi-locus molecular datasets. Here we use molecular species delimitation tools that either quantify differences in intra- and interspecific variability of loci, or divergence times within and between species, or perform coalescent species tree inference to estimate species-level entities in molecular genetic datasets. We benchmark results from these methods against 14 morphologically readily differentiable species of a well-defined subgroup of the diverse Drusinae subfamily (Trichoptera, Limnephilidae). Using a 3798 bp (6 loci) molecular data set we aim to corroborate a geographically isolated new species by integrating comparative morphological studies and molecular taxonomy. Our results indicate that only multi-locus species delimitation provides taxonomically relevant information. The data further corroborate the new species Drusus zivici sp. nov. We provide differential diagnostic characters and describe the male, female and larva of this new species and discuss diversity patterns of Drusinae in the Balkans. We further discuss potential and significance of molecular species delimitation. Finally we argue that enhancing collaborative integrative taxonomy will accelerate assessment of global diversity and completion of reference libraries for applied fields, e.g., conservation and biomonitoring.
-
Decrease in toe pinch force in male type 2 diabetic patients with diabetic nephropathy.
Kataoka, Hiroaki; Miyatake, Nobuyuki; Kitayama, Naomi; Murao, Satoshi; Tanaka, Satoshi
2018-06-01
The purpose of this cross-sectional study was to investigate the toe pinch force (TPF) of type 2 diabetic patients with diabetic nephropathy by disease stage, and to clarify the factors affecting the TPF. Seventy-four men with diabetic nephropathy (age: 62.7 ± 8.9 years, duration of diabetes: 14.2 ± 8.6 years) were enrolled. According to the staging of diabetic nephropathy, TPF and knee extension force (KEF) were compared among three groups: normoalbuminuria, microalbuminuria, and overt nephropathy. In addition, we investigated factors influencing TPF and KEF by performing multiple regression analysis. Normoalbuminuria group, microalbuminuria group, and overt nephropathy group included 26, 25, and 23 patients, respectively. The TPF of the overt nephropathy group (3.15 ± 0.75 kg) was significantly lower than that of the normoalbuminuria (4.2 ± 0.7 kg, p < 0.001) and microalbuminuria groups (3.65 ± 0.81 kg, p = 0.022). The KEF of the overt nephropathy group (37.1 ± 8.3 kgf) was significantly lower than that of the normoalbuminuria group (44.8 ± 8.3 kgf, p = 0.010). Multiple regression analysis revealed that diabetic polyneuropathy (DPN) and diabetic nephropathy were determinant factors of the TPF; and age, body mass index, and diabetic nephropathy were determinant factors of the KEF. We found in male patients with diabetic nephropathy, the TPF and KEF decreased with progression of diabetic nephropathy. Furthermore, our findings suggest diabetic nephropathy and DPN are critically involved in the reduction of TPF and KEF.
-
Conflict Containment in the Balkans: Testing Extended Deterrence.
1995-03-01
STATEMENT 12b. DISTRIBUTION CODE Approved for public release; distribution is unlimited. 13. ABSTRACT This thesis critically analyzes a prominent theoretical...Containment 15. NUMBER OF in the Balkans; Deterrence; Coercive Diplomacy; Balance of Forces. PAGES: 161 16. PRICE CODE 17. SECURITY CLASSIFI- 18. SECURITY...Department of National Security Affai sAccesion For NTIS CRA&I DTtC TAB Unannounced Justifca ........... By- Distribution Availability Codes Avail and/or Dist
-
Acute oxalate nephropathy after ingestion of star fruit.
Chen, C L; Fang, H C; Chou, K J; Wang, J S; Chung, H M
2001-02-01
Acute oxalate nephropathy associated with ingestion of star fruit (carambola) has not been reported before. We report the first two cases. These patients developed nausea, vomiting, abdominal pain, and backache within hours of ingesting large quantities of sour carambola juice; then acute renal failure followed. Both patients needed hemodialysis for oliguric acute renal failure, and pathologic examinations showed typical changes of acute oxalate nephropathy. The renal function recovered 4 weeks later without specific treatment. Sour carambola juice is a popular beverage in Taiwan. The popularity of star fruit juice is not compatible with the rare discovery of star fruit-associated acute oxalate nephropathy. Commercial carambola juice usually is prepared by pickling and dilution processes that reduce oxalate content markedly, whereas pure fresh juice or mild diluted postpickled juice for traditional remedies, as used in our cases, contain high quantities of oxalate. An empty stomach and dehydrated state may pose an additional risk for development of renal injury. To avoid acute oxalate nephropathy, pure sour carambola juice or mild diluted postpickled juice should not be consumed in large amounts, especially on an empty stomach or in a dehydrated state.
-
The Transformation of the European Educational Discourse in the Balkans
ERIC Educational Resources Information Center
Zmas, Aristotelis
2012-01-01
The transfer of the European educational discourse to particular nation-states is a complex process. The outcomes following this transfer are unclear. This article examines the transfer of the European educational discourse in the Balkans and proposes its richer description through the consideration of the processes of educational democratisation…
-
Improvements in the Management of Diabetic Nephropathy
Dounousi, Evangelia; Duni, Anila; Leivaditis, Konstantinos; Vaios, Vasilios; Eleftheriadis, Theodoros; Liakopoulos, Vassilios
2015-01-01
The burden of diabetes mellitus is relentlessly increasing. Diabetic nephropathy is the most common cause of end-stage renal disease (ESRD) worldwide and a major cause of morbidity and mortality in patients with diabetes. The current standard therapy of diabetic nephropathy involves intensive treatment of hyperglycemia and strict blood pressure control, mainly via blockade of the renin-angiotensin system (RAS). Attention has been drawn to additional beneficial effects of oral hypoglycemic drugs and fibrates on other aspects of diabetic nephropathy. On the other hand, antiproteinuric effects of RAS combination therapy do not seem to enhance the prevention of renal disease progression, and it has been associated with an increased rate of serious adverse events. Novel agents, such as bardoxolone methyl, pentoxifylline, inhibitors of protein kinase C (PKC), sulodexide, pirfenidone, endothelin receptor antagonists, vitamin D supplements, and phosphate binders have been associated with controversial outcomes or significant side effects. Although new insights into the pathogenetic mechanisms have opened new horizons towards novel interventions, there is still a long way to go in the field of DN research. The aim of this review is to highlight the recent progress made in the field of diabetes management based on the existing evidence. The article also discusses novel targets of therapy, with a special focus on the major pathophysiologic mechanisms implicated in the initiation and progression of diabetic nephropathy. PMID:26676665
-
New insights into the pathogenesis of IgA nephropathy.
Yeo, See Cheng; Cheung, Chee Kay; Barratt, Jonathan
2018-05-01
IgA nephropathy is the most common form of glomerulonephritis in many parts of the world and remains an important cause of end-stage renal disease. Current evidence suggests that IgA nephropathy is not due to a single pathogenic insult, but rather the result of multiple sequential pathogenic "hits". An abnormally increased level of circulating poorly O-galactosylated IgA1 and the production of O-glycan-specific antibodies leads to the formation of IgA1-containing immune complexes, and their subsequent mesangial deposition results in inflammation and glomerular injury. While this general framework has formed the foundation of our current understanding of the pathogenesis of IgA nephropathy, much work is ongoing to try to precisely define the genetic, epigenetic, immunological, and molecular basis of IgA nephropathy. In particular, the precise origin of poorly O-galactosylated IgA1 and the inciting factors for the production of O-glycan-specific antibodies continue to be intensely evaluated. The mechanisms responsible for mesangial IgA1 deposition and subsequent renal injury also remain incompletely understood. In this review, we summarize the current understanding of the key steps involved in the pathogenesis of IgA nephropathy. It is hoped that further advances in our understanding of this common glomerulonephritis will lead to novel diagnostic and prognostic biomarkers, and targeted therapies to ameliorate disease progression.
-
Environmental waters and blaNDM-1 in Belgrade, Serbia: endemicity questioned.
Novovic, K; Filipic, B; Veljovic, K; Begovic, J; Mirkovic, N; Jovcic, B
2015-04-01
New Delhi metallo-beta-lactamase-1 (NDM-1) will soon become the most commonly isolated and distributed metallo-beta-lactamase worldwide due to its rapid international dissemination and its ability to be expressed by numerous Gram-negative pathogens. NDM-positive bacteria pose a significant public health threat in the Indian subcontinent and the Balkans, which have been designated as endemic regions. Our study was focused on urban rivers, a lake and springheads as a potential source of NDM-1-producing strains in Serbia, but also as a source of other metallo-beta-lactamases and extended-spectrum beta-lactamase (ESBL) producing bacteria. A total of 69 beta-lactam resistant isolates, belonging to 12 bacterial genera, were collected from 8 out of 10 different locations in Belgrade, of which the most were from a popular recreational site, Ada Ciganlija Lake. Phenotypic tests revealed 7 (10.14%) ESBL-producing isolates and 39 (56.52%) isolates resistant to imipenem, of which 32 were positive for metallo-beta-lactamase (MBL) production. PCR and sequencing revealed the presence of genetic determinants for SHV (3 isolates), DHA-1 (1 isolate) and CMY-2 (1 isolate) beta-lactamases. However, we did not detect any NDM-1-producing strains (previously described cases of NDM-1 from Serbia were limited to Belgrade), so we propose that Serbian NDM-1 is in fact a transplant and a nosocomial, rather than an environmental, issue and that Serbia is not an endemic region for NDM-1. Copyright © 2014 Elsevier B.V. All rights reserved.
-
Spontaneous remission of IgA nephropathy associated with resolution of hepatitis A.
Han, Seung Hyeok; Kang, Ea Wha; Kie, Jeong Hae; Yoo, Tae Hyun; Choi, Kyu Hun; Han, Dae-Suk; Kang, Shin-Wook
2010-12-01
Although most cases of immunoglobulin A (IgA) nephropathy are idiopathic, several diseases are associated with IgA nephropathy. Of these, chronic liver disease resulting from hepatitis B or C virus infection has been reported as a secondary cause of IgA nephropathy. Recently, hepatitis A virus (HAV)-associated kidney disease has received attention because acute kidney injury can occur as a complication of HAV infection, generally caused by acute tubular necrosis or interstitial nephritis. However, unlike IgA nephropathy related to hepatitis B or C, HAV-associated IgA nephropathy is extremely rare and long-term outcomes have not been reported yet. We describe a case of spontaneous remission of IgA nephropathy associated with serologically documented HAV infection. The patient presented with microhematuria and moderate proteinuria, but acute kidney injury did not occur during active hepatic injury. Kidney biopsy specimens clearly showed mesangial IgA deposits with intact tubules and interstitium. Serum liver enzyme levels returned to reference values 1 month after the onset of acute hepatitis, but urinary protein excretion remained increased. Approximately 1 year later, urinary abnormalities were resolved and a second biopsy showed no mesangial IgA deposits. These findings suggest that IgA nephropathy can transiently accompany HAV infection, but may not progress to chronic glomerulonephritis after recovery from HAV. Copyright © 2010 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
-
Modelling Factors of Students' Work in Western Balkan Countries
ERIC Educational Resources Information Center
Savic, Mirko; Kresoja, Milena
2018-01-01
The positive side of employment during studies is the increase of net investments in human capital. The main objective of this paper is to discover factors influencing the work of students in Serbia, Bosnia and Herzegovina and Montenegro and to compare students' employment in these three Western Balkan countries. Quantitative analysis based on…
-
Jablonski, Daniel; Jandzik, David; Mikulíček, Peter; Džukić, Georg; Ljubisavljević, Katarina; Tzankov, Nikolay; Jelić, Dušan; Thanou, Evanthia; Moravec, Jiří; Gvoždík, Václav
2016-05-10
Genetic architecture of a species is a result of historical changes in population size and extent of distribution related to climatic and environmental factors and contemporary processes of dispersal and gene flow. Population-size and range contractions, expansions and shifts have a substantial effect on genetic diversity and intraspecific divergence, which is further shaped by gene-flow limiting barriers. The Balkans, as one of the most important sources of European biodiversity, is a region where many temperate species persisted during the Pleistocene glaciations and where high topographic heterogeneity offers suitable conditions for local adaptations of populations. In this study, we investigated the phylogeographical patterns and demographic histories of four species of semifossorial slow-worm lizards (genus Anguis) present in the Balkan Peninsula, and tested the relationship between genetic diversity and topographic heterogeneity of the inhabited ranges. We inferred phylogenetic relationships, compared genetic structure and historical demography of slow worms using nucleotide sequence variation of mitochondrial DNA. Four Anguis species with mostly parapatric distributions occur in the Balkan Peninsula. They show different levels of genetic diversity. A signature of population growth was detected in all four species but with various courses in particular populations. We found a strong correlation between genetic diversity of slow-worm populations and topographic ruggedness of the ranges (mountain systems) they inhabit. Areas with more rugged terrain harbour higher genetic diversity. Phylogeographical pattern of the genus Anguis in the Balkans is concordant with the refugia-within-refugia model previously proposed for both several other taxa in the region and other main European Peninsulas. While slow-worm populations from the southern refugia mostly have restricted distributions and have not dispersed much from their refugial areas, populations from the extra
-
Of the importance of a leaf: the ethnobotany of sarma in Turkey and the Balkans.
Dogan, Yunus; Nedelcheva, Anely; Łuczaj, Łukasz; Drăgulescu, Constantin; Stefkov, Gjoshe; Maglajlić, Aida; Ferrier, Jonathan; Papp, Nora; Hajdari, Avni; Mustafa, Behxhet; Dajić-Stevanović, Zora; Pieroni, Andrea
2015-04-03
Sarma - cooked leaves rolled around a filling made from rice and/or minced meat, possibly vegetables and seasoning plants - represents one of the most widespread feasting dishes of the Middle Eastern and South-Eastern European cuisines. Although cabbage and grape vine sarma is well-known worldwide, the use of alternative plant leaves remains largely unexplored. The aim of this research was to document all of the botanical taxa whose leaves are used for preparing sarma in the folk cuisines of Turkey and the Balkans. Field studies were conducted during broader ethnobotanical surveys, as well as during ad-hoc investigations between the years 2011 and 2014 that included diverse rural communities in Croatia, Bosnia and Herzegovina, Serbia, Kosovo, Albania, Macedonia, Bulgaria, Romania, and Turkey. Primary ethnobotanical and folkloric literatures in each country were also considered. Eighty-seven botanical taxa, mainly wild, belonging to 50 genera and 27 families, were found to represent the bio-cultural heritage of sarma in Turkey and the Balkans. The greatest plant biodiversity in sarma was found in Turkey and, to less extent, in Bulgaria and Romania. The most commonly used leaves for preparing sarma were those of cabbage (both fresh and lacto-fermented), grape vine, beet, dock, sorrel, horseradish, lime tree, bean, and spinach. In a few cases, the leaves of endemic species (Centaurea haradjianii, Rumex gracilescens, and R. olympicus in Turkey) were recorded. Other uncommon sarma preparations were based on lightly toxic taxa, such as potato leaves in NE Albania, leaves of Arum, Convolvulus, and Smilax species in Turkey, of Phytolacca americana in Macedonia, and of Tussilago farfara in diverse countries. Moreover, the use of leaves of the introduced species Reynoutria japonica in Romania, Colocasia esculenta in Turkey, and Phytolacca americana in Macedonia shows the dynamic nature of folk cuisines. The rich ethnobotanical diversity of sarma confirms the urgent need to
-
Potpara, Tatjana S; Dan, Gheorghe-Andrei; Trendafilova, Elina; Goda, Artan; Kusljugic, Zumreta; Manola, Sime; Music, Ljilja; Musetescu, Rodica; Badila, Elisabeta; Mitic, Gorana; Paparisto, Vilma; Dimitrova, Elena S; Polovina, Marija M; Petranov, Stanislav L; Djergo, Hortensia; Loncar, Daniela; Bijedic, Amira; Brusich, Sandro; Lip, Gregory Y H
2016-02-12
Data on the management of atrial fibrillation (AF) in the Balkan Region are limited. The Serbian AF Association (SAFA) prospectively investigated contemporary 'real-world' AF management in clinical practice in Albania, Bosnia&Herzegovina, Bulgaria, Croatia, Montenegro, Romania and Serbia through a 14-week (December 2014-February 2015) prospective, multicentre survey of consecutive AF patients. We report the results pertinent to stroke prevention strategies. Of 2712 enrolled patients, 2663 (98.2%) with complete data were included in this analysis (mean age 69.1 ± 10.9 years, female 44.6%). Overall, 1960 patients (73.6%) received oral anticoagulants (OAC) and 762 (28.6%) received antiplatelet drugs. Of patients given OAC, 17.2% received non-vitamin K antagonist oral anticoagulants (NOACs). CHA2DS2-VASc score was not significantly associated with OAC use. Of the 'truly low-risk' patients (CHA2DS2-VASc = 0 [males], or 1 [females]) 56.5% received OAC. Time in Therapeutic Range (TTR) was available in only 18.7% of patients (mean TTR: 49.5% ± 22.3%). Age ≥ 80 years, prior myocardial infarction and paroxysmal AF were independent predictors of OAC non-use. Our survey shows a relatively high overall use of OAC in AF patients, but with low quality of vitamin K antagonist therapy and insufficient adherence to AF guidelines. Additional efforts are needed to improve AF-related thromboprophylaxis in clinical practice in the Balkan Region.
-
Kamei, Koichi; Ogura, Masao; Sato, Mai; Ito, Shuichi; Ishikura, Kenji
2016-05-01
As the morphological and immunohistochemical manifestations of immunoglobulin A (IgA) nephropathy and Henoch-Schonlein purpura nephritis (HSPN) are very similar, they are considered to share a common pathogenesis. Although HSPN usually develops after the appearance of anaphylactoid purpura, we have encountered patients whose renal symptoms preceded purpura. We reviewed the clinical courses of patients who were first diagnosed with IgA nephropathy, but developed purpura later, at the National Center for Child Health and Development in Tokyo, Japan. Of the 53 patients who were diagnosed with primary IgA nephropathy at our institute during the study period (March 2002 to July 2015), six (11 %) developed anaphylactoid purpura after the diagnosis of primary IgA nephropathy and therefore met the inclusion criteria. Duration between the onset of nephritis and subsequent appearance of purpura ranged from 5 months to 14 years. One patient reached end-stage renal failure due to IgA nephropathy and developed purpura after renal transplantation. All renal biopsies performed before the appearance of purpura showed mesangial proliferation with predominant IgA deposits. Urinary findings deteriorated in three patients after the appearance of purpura, including one patient who developed rapidly progressive glomerulonephritis. Renal biopsy findings worsened in two patients. At the last observation, two patients showed mild renal insufficiency. Our clinical experience and previous reports support the argument that IgA nephropathy and HSPN are different manifestations of a single disease. Hence, it is acceptable to consider that they are variants of a single disease.
-
Dioxins, furans and dioxin-like PCBs in human blood: causes or consequences of diabetic nephropathy?
Everett, Charles J; Thompson, Olivia M
2014-07-01
Nephropathy, or kidney disease, is a major, potential complication of diabetes. We assessed the association of 6 chlorinated dibenzo-p-dioxins, 9 chlorinated dibenzofurans and 8 polychlorinated biphenyls (PCBs) in blood with diabetic nephropathy in the 1999-2004 National Health and Nutrition Examination Survey (unweighted N=2588, population estimate=117,658,357). Diabetes was defined as diagnosed or undiagnosed (glycohemoglobin ≥ 6.5%) and nephropathy defined as urinary albumin to creatinine ratio >30 mg/g, representing microalbuminuria or macroalbuminuria. For the 8 chemicals analyzed separately, values above the 75th percentile were considered elevated, whereas for the other 15 compounds values above the maximum limit of detection were considered elevated. Seven of 8 dioxins and dioxin-like compounds, analyzed separately, were found to be associated with diabetic nephropathy. The chemicals associated with diabetic nephropathy were: 1,2,3,6,7,8-Hexachlorodibenzo-p-dioxin; 1,2,3,4,6,7,8,9-Octachlorodibenzo-p-dioxin; 2,3,4,7,8-Pentachlorodibenzofuran; PCB 126; PCB 169; PCB 118; and PCB 156. Three of the 8 dioxins and dioxin-like compounds; 1,2,3,4,6,7,8,9-Octachlorodibenzo-p-dioxin; 2,3,4,7,8-Pentachlorodibenzofuran and PCB 118; expressed as log-transformed continuous variables; were associated with diabetes without nephropathy. When 4 or more of the 23 chemicals were elevated the odds ratios were 7.00 (95% CI=1.80-27.20) for diabetic nephropathy and 2.13 (95% CI=0.95-4.78) for diabetes without nephropathy. Log-transformed toxic equivalency (TEQ) was associated with both diabetic nephropathy, and diabetes without nephropathy, the odds ratios were 2.35 (95% CI=1.57-3.52) for diabetic nephropathy, and 1.44 (95% CI=1.11-1.87) for diabetes without nephropathy. As the kidneys function to remove waste products from the blood, diabetic nephropathy could be either the cause or the consequence (or both) of exposure to dioxins, furans and dioxin-like PCBs. Copyright © 2014
-
3 CFR - Continuation of the National Emergency With Respect to the Western Balkans
Code of Federal Regulations, 2011 CFR
2011-01-01
... year the national emergency with respect to the Western Balkans. This notice shall be published in the Federal Register and transmitted to the Congress.BARACK OBAMATHE WHITE HOUSE, June 8, 2010. ...
-
NASA Astrophysics Data System (ADS)
Kounov, Alexandre; Gerdjikov, Ianko; Vangelov, Dian; Balkanska, Eleonora; Lazarova, Anna; Georgiev, Stoyan; Blunt, Edward; Stockli, Daniel
2017-11-01
The Balkan fold-thrust belt, exposed in Bulgaria and north-east Serbia, is part of the north-east vergent segment of the bi-vergent Eastern Mediterranean Alpine orogen. It was formed during two distinct compressional stages; the first one lasted from the Middle Jurassic to the Early Cretaceous and the second from Late Cretaceous to the Paleogene. Although the compressional tectonic evolution of the Balkan fold-thrust belt since the Middle Jurassic and during most of the Mesozoic is relatively well studied, the final exhumation of the rocks of the belt during the Cenozoic has remained poorly understood. Here, we present the first thermochronological constraints, based on fission-track and [U-Th-(Sm)]/He analysis, showing that along the central part of the belt syn- to post-orogenic extension could have started as early as the middle Eocene. Low-temperature thermochronological analysis of samples collected from three areas reveals at least two phases of increased cooling and exhumation during the Cenozoic. The first exhumation phase took place between 44 and 30 Ma and appears to be related to the syn- to post-orogenic collapse coeval with the earliest Cenozoic extensional stage observed across the southern Balkan Peninsula. A period of relative quiescence (between 30 and 25 Ma) is followed by the next cooling stage, between 25 and 20 Ma, which appears to be related to late Oligocene to early Miocene crustal extension across the Balkan Peninsula. Extension accommodated by the late Miocene to Recent age Sub-Balkan Graben System does not appear to have produced exhumation of rocks from beneath 2-4 km depth, as it was not detected by the low-temperature thermochronological methods applied in this study.
-
An Examination of Long-Term Environmental-Social Dynamics in the Balkans
NASA Astrophysics Data System (ADS)
Kulkarni, C.; Boger, R. A.
2015-12-01
This study examines the interactions of environmental and social dynamics in Central Balkans over the past millennium, a period that experienced three major climatic phases (Medieval Climate Anomaly, Little Ice Age, and the warm 20th century). Meanwhile, the same period witnessed a complex human history with the emergence-rise-decline of the Ottoman Empire and subsequent socio-political events (e.g. wars, famines, migrations). Environmental datasets for the analysis include biological proxies (pollen, spores, and charcoal), geochemical signals through X-ray fluorescence (XRF), and a detailed chronology based on AMS 14C dating of two western and central Serbian lakes while social datasets include historic population data, land use, settlement patterns, and critical historic events derived from a review of the literature and local archives. Among the environmental datasets, indigenous tree and herbaceous pollen from these Central Balkans records demonstrate fluctuations in woodland-grassland dynamics whereas potassium and titanium counts obtained through XRF act as a proxy for surface erosion and clastic input into the lakes. Microscopic charcoal, cereal pollen and subordinate anthropogenic pollen (e.g. cultivated fruits and vegetables) are used to distinguish strong human impact over the landscape. These key anthropogenic indicators create a more thorough social component of the analysis in association with the social datasets. After reconstructing the individual time series for each environmental and social dataset, the two Central Balkan records are correlated in order to identify the environmental and social homogeneity and heterogeneity patterns occurring at shorter and longer timescales during the period. Results provide insights on how a region responds to social and environmental stressors and our approach demonstrates ways to integrate natural and social science system research.
-
Bostrom, Meredith A.; Kao, W.H. Linda; Li, Man; Abboud, Hanna E.; Adler, Sharon G.; Iyengar, Sudha K.; Kimmel, Paul L.; Hanson, Robert L.; Nicholas, Susanne B.; Rasooly, Rebekah S.; Sedor, John R.; Coresh, Josef; Kohn, Orly F.; Leehey, David J.; Thornley-Brown, Denyse; Bottinger, Erwin P.; Lipkowitz, Michael S.; Meoni, Lucy A.; Klag, Michael J.; Lu, Lingyi; Hicks, Pamela J.; Langefeld, Carl D.; Parekh, Rulan S.; Bowden, Donald W.; Freedman, Barry I.
2011-01-01
Background African Americans (AAs) have increased susceptibility to non-diabetic nephropathy relative to European Americans. Study Design Follow-up of a pooled genome-wide association study (GWAS) in AA dialysis patients with nondiabetic nephropathy; novel gene-gene interaction analyses. Setting & Participants Wake Forest sample: 962 AA nondiabetic nephropathy cases; 931 non-nephropathy controls. Replication sample: 668 Family Investigation of Nephropathy and Diabetes (FIND) AA nondiabetic nephropathy cases; 804 non-nephropathy controls. Predictors Individual genotyping of top 1420 pooled GWAS-associated single nucleotide polymorphisms (SNPs) and 54 SNPs in six nephropathy susceptibility genes. Outcomes APOL1 genetic association and additional candidate susceptibility loci interacting with, or independently from, APOL1. Results The strongest GWAS associations included two non-coding APOL1 SNPs, rs2239785 (odds ratio [OR], 0.33; dominant; p = 5.9 × 10−24) and rs136148 (OR, 0.54; additive; p = 1.1 × 10−7) with replication in FIND (p = 5.0 × 10−21 and 1.9 × 10−05, respectively). Rs2239785 remained significantly associated after controlling for the APOL1 G1 and G2 coding variants. Additional top hits included a CFH SNP(OR from meta-analysis in above 3367 AA cases and controls, 0.81; additive; p = 6.8 × 10−4). The 1420 SNPs were tested for interaction with APOL1 G1 and G2 variants. Several interactive SNPs were detected, the most significant was rs16854341 in the podocin gene (NPHS2) (p = 0.0001). Limitations Non-pooled GWAS have not been performed in AA nondiabetic nephropathy. Conclusions This follow-up of a pooled GWAS provides additional and independent evidence that APOL1 variants contribute to nondiabetic nephropathy in AAs and identified additional associated and interactive non-diabetic nephropathy susceptibility genes. PMID:22119407
-
Association of Haemostatic and Inflammatory Biomarkers with Nephropathy in Type 1 Diabetes Mellitus.
Domingueti, Caroline Pereira; Fóscolo, Rodrigo Bastos; Reis, Janice Sepúlveda; Campos, Fernanda Magalhães Freire; Dusse, Luci Maria S; Carvalho, Maria das Graças; Braga Gomes, Karina; Fernandes, Ana Paula
2016-01-01
This study aimed at investigating the association between haemostatic biomarkers, proinflammatory, and anti-inflammatory cytokines with chronic kidney disease in type 1 diabetic patients. Patients were divided into two groups: with nephropathy (albuminuria ≥ 30 mg/g and/or GFR < 60 mL/min/1.73 m(2)), n = 65; and without nephropathy (albuminuria < 30 mg/g and GFR ≥ 60 mL/min/1.73 m(2)), n = 60. INF-γ, IL-6, IL-10, and TNF-α plasma levels were determined by flow cytometry. VWF, ADAMTS13 antigen, and D-Dimer plasma levels were determined by enzyme-linked immunosorbent assay and ADAMTS13 activity was assessed by fluorescence resonance energy transfer assay. Elevated levels of INF-γ, VWF, ADAMTS13 antigen, D-Dimer, and reduced ADAMTS13 activity/antigen ratio were observed in patients with nephropathy as compared to those without nephropathy (P = 0.001, P < 0.001, P < 0.001, P < 0.001, and P < 0.001, resp.). Cytokines and haemostatic biomarkers remained associated with nephropathy after adjustments (use of statin, acetylsalicylic acid, angiotensin converting enzyme inhibitor, and angiotensin antagonist). INF-γ, TNF-α, and IL-10 significantly correlated with haemostatic biomarkers. Inflammatory and hypercoagulability status are associated with nephropathy in type 1 diabetes mellitus and an interrelationship between them may play an important role in pathogenesis of diabetic nephropathy.
-
Association of Haemostatic and Inflammatory Biomarkers with Nephropathy in Type 1 Diabetes Mellitus
Domingueti, Caroline Pereira; Fóscolo, Rodrigo Bastos; Reis, Janice Sepúlveda; Campos, Fernanda Magalhães Freire; Dusse, Luci Maria S.; Carvalho, Maria das Graças; Braga Gomes, Karina; Fernandes, Ana Paula
2016-01-01
This study aimed at investigating the association between haemostatic biomarkers, proinflammatory, and anti-inflammatory cytokines with chronic kidney disease in type 1 diabetic patients. Patients were divided into two groups: with nephropathy (albuminuria ≥ 30 mg/g and/or GFR < 60 mL/min/1.73 m2), n = 65; and without nephropathy (albuminuria < 30 mg/g and GFR ≥ 60 mL/min/1.73 m2), n = 60. INF-γ, IL-6, IL-10, and TNF-α plasma levels were determined by flow cytometry. VWF, ADAMTS13 antigen, and D-Dimer plasma levels were determined by enzyme-linked immunosorbent assay and ADAMTS13 activity was assessed by fluorescence resonance energy transfer assay. Elevated levels of INF-γ, VWF, ADAMTS13 antigen, D-Dimer, and reduced ADAMTS13 activity/antigen ratio were observed in patients with nephropathy as compared to those without nephropathy (P = 0.001, P < 0.001, P < 0.001, P < 0.001, and P < 0.001, resp.). Cytokines and haemostatic biomarkers remained associated with nephropathy after adjustments (use of statin, acetylsalicylic acid, angiotensin converting enzyme inhibitor, and angiotensin antagonist). INF-γ, TNF-α, and IL-10 significantly correlated with haemostatic biomarkers. Inflammatory and hypercoagulability status are associated with nephropathy in type 1 diabetes mellitus and an interrelationship between them may play an important role in pathogenesis of diabetic nephropathy. PMID:26770985
-
Long Non-Coding RNA CASC2 Improves Diabetic Nephropathy by Inhibiting JNK Pathway.
Yang, Huihui; Kan, Quan E; Su, Yong; Man, Hua
2018-06-11
It's known that long non-coding RNA CASC2 overexpression inhibit the JNK pathway in some disease models, while JNK pathway activation exacerbates diabetic nephropathy. Therefore we speculate that long non-coding RNA CASC2 can improve diabetic nephropathy by inhibiting JNK pathway. Thus, our study was carried out to investigate the involvement of CASC2 in diabetic nephropathy. We found that serum level of CASC2 was significantly lower in diabetic nephropathy patients than in normal people, and serum level of CASC2 showed no significant correlations with age, gender, alcohol consumption and smoking habits, but was correlated with course of disease. ROC curve analysis showed that serum level of CASC2 could be used to accurately predict diabetic nephropathy. Diabetes mellitus has many complications. This study also included a series of complications of diabetes, such as diabetic retinopathy, diabetic ketoacidosis, diabetic foot infections and diabetic cardiopathy, while serum level of CASC2 was specifically reduced in diabetic nephropathy. CASC2 expression level decreased, while JNK1 phosphorylation level increased in mouse podocyte cells treated with high glucose. CASC2 overexpression inhibited apoptosis of podocyte cells and reduced phosphorylation level of JNK1. We conclude that long non-coding RNA CASC2 may improve diabetic nephropathy by inhibiting JNK pathway. © Georg Thieme Verlag KG Stuttgart · New York.
-
Traditional wound-healing plants used in the Balkan region (Southeast Europe).
Jarić, Snežana; Kostić, Olga; Mataruga, Zorana; Pavlović, Dragana; Pavlović, Marija; Mitrović, Miroslava; Pavlović, Pavle
2018-01-30
The geographical and ecological specificity of the Balkan Peninsula has resulted in the development of a distinct diversity of medicinal plants. In the traditional culture of the Balkan peoples, plants have medicinal, economic and anthropological/cultural importance, which is reflected in the sound knowledge of their diversity and use. This study analyses the traditional use of medicinal plants in the treatment of wounds and the pharmacological characteristics of the most frequently used species. A detailed analysis of the literature related to ethnobhe uses of medicinal plants in the Balkan region was carried out. Twenty-five studies were analysed and those plants used for the treatment of wounds were singled out. An ethnobotanical analysis showed that 128 plant species (105 wild, 22 cultivated and 1 wild/cultivated) are used in the treatment of wounds. Their application is external, in the form of infusions, decoctions, tinctures, syrups, oils, ointments, and balms, or direct to the skin. Among those plants recorded, the most commonly used are Plantago major, Hypericum perforatum, Plantago lanceolata, Achillea millefolium, Calendula officinalis, Sambucus nigra, Tussilago farfara and Prunus domestica. The study showed that the traditional use of plants in wound healing is confirmed by in vitro and/or in vivo studies for P. major and P. lanceolata (3 laboratory studies for P. major and 2 for P. lanceolata), H. perforatum (5 laboratory studies and 3 clinical trials), A. millefolium (3 laboratory studies and one clinical trial), C. officinalis (6 laboratory studies and 1 clinical trial), S. nigra (3 laboratory studies) and T. farfara (one laboratory study). The beneficial effects of using medicinal plants from the Balkan region to heal wounds according to traditional practices have been proven in many scientific studies. However, information on the quantitative benefits to human health of using herbal medicines to heal wounds is still scarce or fragmented, hindering
-
Mitochondrial Reactive Oxygen Species and Kidney Hypoxia in the Development of Diabetic Nephropathy
Schiffer, Tomas A.; Friederich-Persson, Malou
2017-01-01
The underlying mechanisms in the development of diabetic nephropathy are currently unclear and likely consist of a series of dynamic events from the early to late stages of the disease. Diabetic nephropathy is currently without curative treatments and it is acknowledged that even the earliest clinical manifestation of nephropathy is preceded by an established morphological renal injury that is in turn preceded by functional and metabolic alterations. An early manifestation of the diabetic kidney is the development of kidney hypoxia that has been acknowledged as a common pathway to nephropathy. There have been reports of altered mitochondrial function in the diabetic kidney such as altered mitophagy, mitochondrial dynamics, uncoupling, and cellular signaling through hypoxia inducible factors and AMP-kinase. These factors are also likely to be intertwined in a complex manner. In this review, we discuss how these pathways are connected to mitochondrial production of reactive oxygen species (ROS) and how they may relate to the development of kidney hypoxia in diabetic nephropathy. From available literature, it is evident that early correction and/or prevention of mitochondrial dysfunction may be pivotal in the prevention and treatment of diabetic nephropathy. PMID:28443030
-
Mitochondrial Reactive Oxygen Species and Kidney Hypoxia in the Development of Diabetic Nephropathy.
Schiffer, Tomas A; Friederich-Persson, Malou
2017-01-01
The underlying mechanisms in the development of diabetic nephropathy are currently unclear and likely consist of a series of dynamic events from the early to late stages of the disease. Diabetic nephropathy is currently without curative treatments and it is acknowledged that even the earliest clinical manifestation of nephropathy is preceded by an established morphological renal injury that is in turn preceded by functional and metabolic alterations. An early manifestation of the diabetic kidney is the development of kidney hypoxia that has been acknowledged as a common pathway to nephropathy. There have been reports of altered mitochondrial function in the diabetic kidney such as altered mitophagy, mitochondrial dynamics, uncoupling, and cellular signaling through hypoxia inducible factors and AMP-kinase. These factors are also likely to be intertwined in a complex manner. In this review, we discuss how these pathways are connected to mitochondrial production of reactive oxygen species (ROS) and how they may relate to the development of kidney hypoxia in diabetic nephropathy. From available literature, it is evident that early correction and/or prevention of mitochondrial dysfunction may be pivotal in the prevention and treatment of diabetic nephropathy.
-
Japan Diabetic Nephropathy Cohort Study: study design, methods, and implementation.
Furuichi, Kengo; Shimizu, Miho; Toyama, Tadashi; Koya, Daisuke; Koshino, Yoshitaka; Abe, Hideharu; Mori, Kiyoshi; Satoh, Hiroaki; Imanishi, Masahito; Iwano, Masayuki; Yamauchi, Hiroyuki; Kusano, Eiji; Fujimoto, Shouichi; Suzuki, Yoshiki; Okuda, Seiya; Kitagawa, Kiyoki; Iwata, Yasunori; Kaneko, Shuichi; Nishi, Shinichi; Yokoyama, Hitoshi; Ueda, Yoshihiko; Haneda, Masakazu; Makino, Hirofumi; Wada, Takashi
2013-12-01
Diabetic nephropathy, leading to end-stage renal disease, has a considerable impact on public health and the social economy. However, there are few national registries of diabetic nephropathy in Japan. The aims of this prospective cohort study are to obtain clinical data and urine samples for revising the clinical staging of diabetic nephropathy, and developing new diagnostic markers for early diabetic nephropathy. The Japanese Society of Nephrology established a nationwide, web-based, and prospective registry system. On the system, there are two basic registries; the Japan Renal Biopsy Registry (JRBR), and the Japan Kidney Disease Registry (JKDR). In addition to the two basic registries, we established a new prospective registry to the system; the Japan Diabetic Nephropathy Cohort Study (JDNCS), which collected physical and laboratory data. We analyzed the data of 321 participants (106 female, 215 male; average age 65 years) in the JDNCS. Systolic and diastolic blood pressure was 130.1 and 72.3 mmHg, respectively. Median estimated glomerular filtration rate (eGFR) was 33.3 ml/min/1.73 m(2). Proteinuria was 1.8 g/gCr, and serum levels of albumin were 3.6 g/dl. The majority of the JDNCS patients presented with preserved eGFR and low albuminuria or low eGFR and advanced proteinuria. In the JRBR and JKDR registries, 484 and 125 participants, respectively, were enrolled as having diabetes mellitus. In comparison with the JRBR and JKDR registries, the JDNCS was characterized by diabetic patients presenting with low proteinuria with moderately preserved eGFR. There are few national registries of diabetic nephropathy to evaluate prognosis in Japan. Future analysis of the JDNCS will provide clinical insights into the epidemiology and renal and cardiovascular outcomes of type 2 diabetic patients in Japan.
-
Deciphering the balkan Enigma: Using History to Inform Policy
1993-03-01
University Press, 1973. After long experience with German interference in Serbian/Yugoslav affairs (1878, 1908, 1914 - 1918 ) it should not be surprising that... 1914 - 1918 , ed. Djordjevicý, Santa Barbara: CLID Books, 1980. 151. James Gow, "Deconstructing Yugoslavia," Survival, Vol. 33, Nc. 4, July-August 1992, p...of political institutions witnin tine Balkans anu io0w these political dev, ’ýpments intluence current events. Historical perspective gained is used
-
The Balkan beam - Florschütz frame and its use during the Great War.
Fatović-Ferenčić, Stella; Pećina, Marko
2014-10-01
We remember the military medical practice of Croatian surgeon, Vatroslav Florschütz (1879-1967), known for his invention of the traction frame for repositioning bone fracture fragments of the upper and lower extremities. The method, known as the Balkan frame / beam or Balkan splint, was introduced and published in 1911 and used in war medicine thereafter. The memory of this invention adds to our orthopaedic heritage and sheds light on its creator working under the most demanding war circumstances. On the occasion of the 100th anniversary of the outbreak of World War I, reminiscence of Florschütz's war experience, his orthopaedic innovation and other innovations contributes to our understanding of human efforts to save lives and restore bodily function of the wounded during wars.
-
The role of IL-18 in type 1 diabetic nephropathy: The problem and future treatment.
Elsherbiny, Nehal M; Al-Gayyar, Mohammed M H
2016-05-01
Diabetic vascular complication is a leading cause of diabetic nephropathy, a progressive increase in urinary albumin excretion coupled with elevated blood pressure leading to declined glomerular filtration and eventually end stage renal failure. There is growing evidence that activated inflammation is contributing factor to the pathogenesis of diabetic nephropathy. Meanwhile, IL-18, a member of the IL-1 family of inflammatory cytokines, is involved in the development and progression of diabetic nephropathy. However, the benefits derived from the current therapeutics for diabetic nephropathy strategies still provide imperfect protection against renal progression. This imperfection points to the need for newer therapeutic agents that have potential to affect primary mechanisms contributing to the pathogenesis of diabetic nephropathy. Therefore, the recognition of IL-18 as significant pathogenic mediators in diabetic nephropathy leaves open the possibility of new potential therapeutic targets. Copyright © 2016 Elsevier Ltd. All rights reserved.
-
Public Regulatory Arrangements for Private Higher Education in the Western Balkans
ERIC Educational Resources Information Center
Papadimitriou, Antigoni; Levy, Daniel C.; Stensaker, Bjørn; Kanazir, Sanja
2017-01-01
The article presents an analysis of the developments of higher education laws and regulations in the Western Balkans for the period 1990-2015, with the aim of mapping the regulatory arrangements for the private higher education sector and to explore the relationship between public and private higher education in the region. Based on a conceptual…
-
Physical self-concept of adolescents in Western Balkan countries: a pilot study.
Janić, Snežana Radisavljević; Jurak, Gregor; Milanović, Ivana; Lazarević, Dušanka; Kovač, Marjeta; Novak, Dario
2014-10-01
The aim of this study was to explore physical self-concept of adolescents of the Western Balkans (Serbia, Slovenia, Croatia, and Bosnia and Herzegovina) according to sex and country. The participants were 2,606 students, ages 13 and 14 years (M = 13.5, SD = 0.9). The Physical Self-Description Questionnaire (PSDQ) was used to assess multidimensional physical self-concept. The results show the interaction of sex and country for three dimensions of physical self-concept (Appearance, Global Physical Self-Concept, and Self-Esteem). It was shown that female and male adolescents' perception of physical appearance, self-esteem, and global physical self-concept is more susceptible to influences of socio-cultural factors in the monitored countries. In all other dimensions of Physical self-concept, sex differences were consistently manifested in favour of male adolescents, except in Flexibility. Regardless of adolescents' sex, under the increasing influence of Western culture in the Western Balkan countries, adolescents more critically evaluate their body and motor abilities.
-
Dental calculus reveals Mesolithic foragers in the Balkans consumed domesticated plant foods.
Cristiani, Emanuela; Radini, Anita; Edinborough, Marija; Borić, Dušan
2016-09-13
Researchers agree that domesticated plants were introduced into southeast Europe from southwest Asia as a part of a Neolithic "package," which included domesticated animals and artifacts typical of farming communities. It is commonly believed that this package reached inland areas of the Balkans by ∼6200 calibrated (cal.) BC or later. Our analysis of the starch record entrapped in dental calculus of Mesolithic human teeth at the site of Vlasac in the Danube Gorges of the central Balkans provides direct evidence that already by ∼6600 cal. BC, if not earlier, Late Mesolithic foragers of this region consumed domestic cereals, such as Triticum monococcum, Triticum dicoccum, and Hordeum distichon, which were also the main crops found among Early Neolithic communities of southeast Europe. We infer that "exotic" Neolithic domesticated plants were introduced to southern Europe independently almost half a millennium earlier than previously thought, through networks that enabled exchanges between inland Mesolithic foragers and early farming groups found along the Aegean coast of Turkey.
-
Coexistence of Fabry disease and IgA nephropathy: a report of two cases.
Yin, G; Wu, Y; Zeng, C-H; Chen, H-P; Liu, Z-H
2014-12-01
Coexistence of Fabry disease and IgA nephropathy is rare. Moreover, the coexisting Fabry disease may be unrecognized due to unapparent clinical manifestations. We described two cases with coexisting Fabry disease and IgA nephropathy. The clinicopathological features of these two patients were studied. A 54-year-old male presented with proteinuria, hematuria, and hypertension, and a 33-year-old male presented with proteinuria without clinical signs or family history of Fabry disease. Both of them were diagnosed with IgA nephropathy at admission, whereas Fabry disease was not suspected. Subsequent immunofluorescent study confirmed the diagnosis of IgA nephropathy by showing positive staining for IgA and complement C3 in the mesangium. Meanwhile, light microscopy showed remarkable vacuolation of podocytes with mild mesangial expansion, which was characteristic of Fabry nephropathy. Further examination of toluidine blue-stained semi-thin sections and electron microscopy demonstrated blue bodies and myelin figures in the cytoplasm of podocytes, respectively. The diagnosis of coexisting Fabry disease was finally established based on deficient α-galactosidase A activity in both patients. This case study is an important reminder of the role of kidney biopsy as an indicator of Fabry disease and its rare coexistence with IgA nephropathy.
-
Potpara, Tatjana S; Trendafilova, Elina; Dan, Gheorghe-Andrei; Goda, Artan; Kusljugic, Zumreta; Manola, Sime; Music, Ljilja; Gjini, Viktor; Pojskic, Belma; Popescu, Mircea Ioakim; Georgescu, Catalina Arsenescu; Dimitrova, Elena S; Kamenova, Delyana; Ekmeciu, Uliks; Mrsic, Denis; Nenezic, Ana; Brusich, Sandro; Milanov, Srdjan; Zeljkovic, Ivan; Lip, Gregory Y H
2017-08-01
Data on management of atrial fibrillation (AF) in the Balkan Region are scarce. To capture the patterns in AF management in contemporary clinical practice in the Balkan countries a prospective survey was conducted between December 2014 and February 2015, and we report results pertinent to the use of non-vitamin K antagonist oral anticoagulants (NOACs). A 14-week prospective, multicenter survey of consecutive AF patients seen by cardiologists or internal medicine specialists was conducted in Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Montenegro, Romania, and Serbia (a total of about 50 million inhabitants). Of 2712 enrolled patients, 2663 (98.2%) had complete data relevant to oral anticoagulant (OAC) use (mean age 69.1 ± 10.9 years, female 44.6%). Overall, OAC was used in 1960 patients (73.6%) of whom 338 (17.2%) received NOACs. Malignancy [odds ratio (OR), 95% confidence interval (CI) 2.06, 1.20-3.56], rhythm control (OR 1.64, 1.25-2.16), and treatment by cardiologists were independent predictors of NOAC use (OR 2.32, 1.51-3.54) [all p < 0.01)], whilst heart failure and valvular disease were negatively associated with NOAC use (both p < 0.01). Individual stroke and bleeding risk were not significantly associated with NOAC use on multivariate analysis. NOACs are increasingly used in AF patients in the Balkan Region, but NOAC use is predominantly guided by factors other than evidence-based decision-making (e.g., drug availability on the market or reimbursement policy). Efforts are needed to establish an evidence-based approach to OAC selection and to facilitate the optimal use of OAC, thus improving the outcomes in AF patients in this large region.
-
Has RAAS Blockade Reached Its Limits in the Treatment of Diabetic Nephropathy?
Majewski, Collen; Bakris, George L
2016-04-01
Medications that block the renin-angiotensin-aldosterone system (RAAS) are a cornerstone of diabetic nephropathy treatment. These agents play an important role in slowing the nephropathy progression in patients with diabetes. Clinical outcome trials that investigated use of these drug classes in patients with diabetic nephropathy have demonstrated clinical significant benefit in slowing nephropathy progression only in people with >300 mg/day of proteinuria. Thus, guidelines mandate their use in such patients. Conversely, combinations of RAAS blocking agents in these patients can worsen renal outcomes. Moreover, use of RAAS blockers in patients with a glomerular filtration rate below 45 mL/min/1.73 m(2) is limited by hyperkalemia. New agents that predictably bind excess potassium in the colon offer the possibility of extending RAAS inhibitor use in advanced chronic kidney disease (CKD) to allow evaluation of RAAS blockade for nephropathy and cardiovascular outcomes. These new potassium-binding agents may provide an opportunity to continue full-dose RAAS inhibition and assess if the benefits of RAAS blockade seen in stage 3 CKD can be extrapolated to persons with stages 4 and 5 CKD, not previously tested due to hyperkalemia.
-
Madsen, T; Sadowa Vedtofte, M; Nordentoft, M; Ravnborg Nissen, L; Bo Andersen, S
2017-06-01
Insight on how different missions have impacted rates of mental health service (MHS) utilization is unexplored. We compared postdeployment MHS utilization in a national cohort of first-time deployed to missions in Balkan, Iraq, and Afghanistan respectively. A prospective national cohort study of 13 246 first-time deployed in the period 1996 through 2012 to missions in Balkan area, Iraq, or Afghanistan respectively. Soldiers 'MHS utilization was also compared with a 5:1 sex-, age-, and calendar year-matched never-deployed background population. Postdeployment utilization of MHS was retrieved from national coverage registers. Using Cox survival analyses, participants were followed and compared with regard to receiving three different types of psychiatric services: (i) admission to psychiatric hospital, (ii) psychiatric outpatient contact, and (iii) prescriptions of psychotropics. Utilizing of psychiatric outpatient services and psychotropics was significantly higher in first-time deployed to Iraq and Afghanistan compared with deployed to Balkan. However, the rate of postdeployment admission to psychiatric hospital did not differ between missions. Postdeployment rates of psychiatric admission and psychiatric outpatient treatment were significantly higher in Afghanistan-deployed personnel compared with the background population. Utilization of MHS differed significantly between mission areas and was highest after the latest mission to Afghanistan. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
-
IgM nephropathy; can we still ignore it.
Vanikar, Aruna
2013-04-01
IgM nephropathy (IgMN) is a relatively less recognized clinico-immunopathological entity in the domain of glomerulonephritis , often thought to be a bridge between minimal change disease and focal segmental glomerulosclerosis. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science has been searched. IgM nephropathy can present as nephritic syndrome or less commonly with subnephrotic proteinuria or rarely hematuria. About 30% patients respond to steroids whereas others are steroid dependent / resistant. They should be given a trial of Rituximab or stem cell therapy. IgM nephropathy (IgMN) is an important and rather neglected pathology responsible for renal morbidity in children and adults in developing countries as compared to developed nations with incidence of 2-18.5% of native biopsies. Abnormal T-cell function with hyperfunctioning suppressor T-cells are believed to be responsible for this disease entity. Approximately one third of the patients are steroid responders where as the remaining two thirds are steroid resistant or dependent. Therapeutic trials including cell therapies targeting suppressor T-cells are required.
-
Paraprotein-Related Kidney Disease: Evaluation and Treatment of Myeloma Cast Nephropathy.
Finkel, Kevin W; Cohen, Eric P; Shirali, Anushree; Abudayyeh, Ala
2016-12-07
Nearly 50% of patients with multiple myeloma develop renal disease, most commonly from AKI caused by cast nephropathy. Development of AKI is associated with poor 1-year survival and reduces the therapeutic options available to patients. There is a great need for more effective therapies. Cast nephropathy is caused by the interaction and aggregation of filtered free light chains and Tamm-Horsfall protein causing intratubular obstruction and damage. The key to treating cast nephropathy is rapid lowering of free light chains, because this correlates with renal recovery. Newer chemotherapy agents rapidly lower free light chains and have been referred to as renoprotective. There is additional great interest in using extracorporeal therapies to remove serum free light chains. Small trials initially showed benefit of therapeutic plasma exchange to improve renal outcomes in cast nephropathy, but a large randomized trial of therapeutic plasma exchange failed to show benefit. A newer technique is extended high-cutoff hemodialysis. This modality uses a high molecular weight cutoff filter to remove free light chains. To date, trials of high-cutoff hemodialysis use in patients with cast nephropathy have been encouraging. However, there are no randomized trials showing the benefit of high-cutoff hemodialysis when used in addition to newer chemotherapeutic regimens. Until these studies are available, high-cutoff hemodialysis cannot be recommended as standard of care. Copyright © 2016 by the American Society of Nephrology.
-
Detection of early nephropathy in Mexican patients with type 2 diabetes mellitus.
Cueto-Manzano, Alfonso M; Cortes-Sanabria, Laura; Martinez-Ramirez, H Ramon; Rojas-Campos, Enrique; Barragan, Graciela; Alfaro, Gilberto; Flores, Jorge; Anaya, Moises; Canales-Munoz, Jose L
2005-08-01
The aims of this study were to determine the prevalence of early nephropathy in patients with type 2 diabetes mellitus (DM2) attending primary care medical units and to identify risk factors for nephropathy in this population. Seven hundred fifty-six patients with DM2 attending 3 primary care medical units were randomly selected. In a first interview, an albuminuria dipstick and a detailed clinical examination were performed, and a blood sample was obtained. If the albuminuria dipstick was positive, then a 24-hour urine collection was obtained within the next 2 weeks to quantify the albuminuria. In the blood sample, glucose, creatinine, and lipids were determined. Glomerular filtration rate was calculated using the Modification of Diet in Renal Disease Study equation. Demographics and medical history were recorded from clinical examination and medical charts. Prevalence of early nephropathy (EN) was 40%, normal function (NF) was found in 31%, and overt nephropathy (ON) in 29%. Patients with more severe kidney damage were older (NF: 54 +/- 10; EN: 60 +/- 11; ON: 63 +/- 10 years, P < 0.05) and had a higher proportion of illiteracy (NF: 11%, EN: 17%; ON: 25%, P < 0.05). The more severe the nephropathy, the longer the median duration of DM2 (NF: 6.0; EN: 7.0; ON: 11.0 years; P < 0.05); the higher the frequency of hypertension (NF: 38%; EN: 52%; ON: 68%; P < 0.05); and the higher the systolic blood pressure (NF: 126 +/- 21; EN: 130 +/- 19; ON: 135 +/- 23 mm Hg; P < 0.05). Both nephropathy groups had a significantly higher proportion of family history of nephropathy (NF: 4%; EN: 9%; ON: 13%) and a higher frequency of cardiovascular disease (NF: 5%; EN: 12%; ON: 25%), whereas only patients with ON had peripheral neuropathy (NF: 21%; EN: 22%; ON: 43%) and retinopathy (NF: 12%; EN: 18%; ON: 42%) more frequently than others. Fasting glucose was poorly controlled in all groups (NF: 186 +/- 70; EN: 173 +/- 62; ON: 183 +/- 73 mg/dL). Large body mass index (NF: 29.3 +/- 5.3; EN
-
Adaptive changes in renal mitochondrial redox status in diabetic nephropathy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Putt, David A.; Zhong, Qing; Lash, Lawrence H., E-mail: l.h.lash@wayne.edu
2012-01-15
Nephropathy is a serious and common complication of diabetes. In the streptozotocin (STZ)-treated rat model of diabetes, nephropathy does not typically develop until 30 to 45 days post-injection, although hyperglycemia occurs within 24 h. We tested the hypothesis that chronic hyperglycemia results in a modest degree of oxidative stress that is accompanied by compensatory changes in certain antioxidants and mitochondrial redox status. We propose that as kidneys progress to a state of diabetic nephropathy, further adaptations occur in mitochondrial redox status. Basic parameters of renal function in vivo and several parameters of mitochondrial function and glutathione (GSH) and redox statusmore » in isolated renal cortical mitochondria from STZ-treated and age-matched control rats were examined at 30 days and 90 days post-injection. While there was no effect of diabetes on blood urea nitrogen, measurement of other, more sensitive parameters, such as urinary albumin and protein, and histopathology showed significant and progressive worsening in diabetic rats. Thus, renal function is compromised even prior to the onset of frank nephropathy. Changes in mitochondrial respiration and enzyme activities indicated existence of a hypermetabolic state. Higher mitochondrial GSH content and rates of GSH transport into mitochondria in kidneys from diabetic rats were only partially due to changes in expression of mitochondrial GSH carriers and were mostly due to higher substrate supply. Although there are few clear indicators of oxidative stress, there are several redox changes that occur early and change further as nephropathy progresses, highlighting the complexity of the disease. Highlights: ►Adaptive changes in renal mitochondrial and redox status in diabetic rats. ►Modest renal dysfunction even prior to onset of nephropathy. ►Elevated concentrations of mitochondrial GSH in diabetic kidneys. ►Change in GSH due partly to increased protein expression of transporter.
-
Tanios, Bassem Y.; Ziyadeh, Fuad N.
2012-01-01
Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. The mainstay of treatment has been glycemic control and blood pressure lowering using agents blocking the renin-angiotensin system. Clinical trials are currently under way using novel agents for the treatment of patients with diabetic nephropathy. Promising agents emerging from some of the completed trials include pirfenidone and bardoxolone methyl, which have been shown in two recent randomized controlled trials in patients with diabetic nephropathy to result in an improved estimated glomerular filtration rate compared to placebo. Also, paricalcitol has been shown to decrease the urinary albumin-to-creatinine ratio, whereas sulodexide failed to do so in a large randomized double-blind placebo-controlled trial. Of note, pyridoxamine has also shown promise in the treatment of diabetic nephropathy if started early in the disease course. These preliminary trials have shown significant promise for managing patients with diabetic nephropathy, sparking active research in this field and providing the rationale for further clinical testing in long-term, hard-outcomes trials. PMID:23599705
-
A story of microalbuminuria and diabetic nephropathy
Roshan, Bijan; Stanton, Robert C.
2013-01-01
Context: It is estimated that more than 346 million people worldwide have diabetes mellitus . By the year 2030, it is predicted that diabetes will become the seventh leading cause of death in the world. Development of chronic kidney disease (CKD) in patients with diabetes adds significantly to the morbidity and mortality and significantly increases health care costs, even before the development of end stage renal disease (ESRD). Evidence acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Results: Diabetic nephropathy (DN) is increasing rapidly worldwide. It is the leading cause of new cases of ESRD in the USA. Interestingly, although DN is the most common cause of ESRD in diabetic patients, diabetes mellitus is also an independent and strong risk factor for ESRD ascribed to causes other than DN (e.g. hypertensive nephropathy). Conclusions: It is important to be aware of the pitfalls of using the urine albumin level in predicting development and progression of diabetic nephropathy in order to treat and advise the patients accurately. Research into finding new markers is rapidly evolving but current progress makes it likely we will be using the urine albumin level for some years into the future. PMID:24475455
-
A story of microalbuminuria and diabetic nephropathy.
Roshan, Bijan; Stanton, Robert C
2013-10-01
It is estimated that more than 346 million people worldwide have diabetes mellitus . By the year 2030, it is predicted that diabetes will become the seventh leading cause of death in the world. Development of chronic kidney disease (CKD) in patients with diabetes adds significantly to the morbidity and mortality and significantly increases health care costs, even before the development of end stage renal disease (ESRD). Evidence acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Diabetic nephropathy (DN) is increasing rapidly worldwide. It is the leading cause of new cases of ESRD in the USA. Interestingly, although DN is the most common cause of ESRD in diabetic patients, diabetes mellitus is also an independent and strong risk factor for ESRD ascribed to causes other than DN (e.g. hypertensive nephropathy). It is important to be aware of the pitfalls of using the urine albumin level in predicting development and progression of diabetic nephropathy in order to treat and advise the patients accurately. Research into finding new markers is rapidly evolving but current progress makes it likely we will be using the urine albumin level for some years into the future.
-
Sato, Atsuhisa
2015-06-01
Diabetes mellitus is a major cause of chronic kidney disease (CKD), and diabetic nephropathy is the most common primary disease necessitating dialysis treatment in the world including Japan. Major guidelines for treatment of hypertension in Japan, the United States and Europe recommend the use of angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers, which suppress the renin-angiotensin system (RAS), as the antihypertensive drugs of first choice in patients with coexisting diabetes. However, even with the administration of RAS inhibitors, failure to achieve adequate anti-albuminuric, renoprotective effects and a reduction in cardiovascular events has also been reported. Inadequate blockade of aldosterone may be one of the reasons why long-term administration of RAS inhibitors may not be sufficiently effective in patients with diabetic nephropathy. This review focuses on treatment in diabetic nephropathy and discusses the significance of aldosterone blockade. In pre-nephropathy without overt nephropathy, a mineralocorticoid receptor antagonist can be used to enhance the blood pressure-lowering effects of RAS inhibitors, improve insulin resistance and prevent clinical progression of nephropathy. In CKD categories A2 and A3, the addition of a mineralocorticoid receptor antagonist to an RAS inhibitor can help to maintain 'long-term' antiproteinuric and anti-albuminuric effects. However, in category G3a and higher, sufficient attention must be paid to hyperkalemia. Mineralocorticoid receptor antagonists are not currently recommended as standard treatment in diabetic nephropathy. However, many studies have shown promise of better renoprotective effects if mineralocorticoid receptor antagonists are appropriately used.
-
Subclinical hypothyroidism and diabetic nephropathy in Iranian patients with type 2 diabetes.
Mansournia, N; Riyahi, S; Tofangchiha, S; Mansournia, M A; Riahi, M; Heidari, Z; Hazrati, E
2017-03-01
Association of subclinical hypothyroidism with type 2 diabetes and its complications has been previously documented. These reports were, however, inconclusive and mainly gathered from Chinese and East Asian populations. In this study, we aimed to determine the prevalence of subclinical hypothyroidism and its relationship with diabetic nephropathy in Iranian individuals with type 2 diabetes, drawn from a white Middle Eastern population with an increasing prevalence of diabetes. In this cross-sectional study, 255 Iranian participants with type 2 diabetes and without history of thyroid disorders were included. Patients with TSH > 4.2 mIU/L and normal T4 were classified as having subclinical hypothyroidism. Diabetic nephropathy was diagnosed based on abnormal 24-h urinary albumin or protein measurements (24-h urinary albumin ≥30 mg/day or 24-h urinary protein ≥150 mg/day). Multivariate logistic regression was employed to obtain the OR for the relationship between subclinical hypothyroidism and diabetic nephropathy. We found that subclinical hypothyroidism and diabetic nephropathy were as prevalent as 18.1 and 41.2 %, respectively, among the participants. We also found that subclinical hypothyroidism was independently associated with higher rates of diabetic nephropathy, after multivariable adjustment (OR [95 % CI] 3.23 [1.42-7.37], p = 0.005). We found that the prevalence of subclinical hypothyroidism in Iranian diabetic population was among the highest rates reported to date. Our data supported the independent association of subclinical hypothyroidism with diabetic nephropathy, calling for further investigations to evaluate their longitudinal associations.
-
Molecular diversity and evolutionary history of rabies virus strains circulating in the Balkans.
McElhinney, L M; Marston, D A; Freuling, C M; Cragg, W; Stankov, S; Lalosevic, D; Lalosevic, V; Müller, T; Fooks, A R
2011-09-01
Molecular studies of European classical rabies viruses (RABV) have revealed a number of geographically clustered lineages. To study the diversity of Balkan RABV, partial nucleoprotein (N) gene sequences were analysed from a unique panel of isolates (n = 210), collected from various hosts between 1972 and 2006. All of the Balkan isolates grouped within the European/Middle East Lineage, with the majority most closely related to East European strains. A number of RABV from Bosnia & Herzegovina and Montenegro, collected between 1986 and 2006, grouped with the West European strains, believed to be responsible for the rabies epizootic that spread throughout Europe in the latter half of the 20th Century. In contrast, no Serbian RABV belonged to this sublineage. However, a distinct group of Serbian fox RABV provided further evidence for the southwards wildlife-mediated movement of rabies from Hungary, Romania and Serbia into Bulgaria. To determine the optimal region for evolutionary analysis, partial, full and concatenated N-gene and glycoprotein (G) gene sequences were compared. Whilst both the divergence times and evolutionary rates were similar irrespective of genomic region, the 95 % highest probability density (HPD) limits were significantly reduced for full N-gene and concatenated NG-gene sequences compared with partial gene sequences. Bayesian coalescent analysis estimated the date of the most common recent ancestor of the Balkan RABV to be 1885 (95 % HPD, 1852-1913), and skyline plots suggested an expansion of the local viral population in 1980-1990, which coincides with the observed emergence of fox rabies in the region.
-
Wang, Ke; Feng, Chenchen; Li, Chenggang; Yao, Jun; Xie, Xiaofeng; Gong, Likun; Luan, Yang; Xing, Guozhen; Zhu, Xue; Qi, Xinming; Ren, Jin
2015-01-01
Exposure to aristolochic acid I (AAI) can lead to aristolochic acid nephropathy (AAN), Balkan endemic nephropathy (BEN) and urothelial cancer. The induction of hepatic CYP1A, especially CYP1A2, was considered to detoxify AAI so as to reduce its nephrotoxicity. We previously found that baicalin had the strong ability to induce CYP1A2 expression; therefore in this study, we examined the effects of baicalin on AAI toxicity, metabolism and disposition, as well as investigated the underlying mechanisms. Our toxicological studies showed that baicalin reduced the levels of blood urea nitrogen (BUN) and creatinine (CRE) in AAI-treated mice and attenuated renal injury induced by AAI. Pharmacokinetic analysis demonstrated that baicalin markedly decreased AUC of AAI in plasma and the content of AAI in liver and kidney. CYP1A induction assays showed that baicalin exposure significantly increased the hepatic expression of CYP1A1/2, which was completely abolished by inhibitors of the Aromatic hydrocarbon receptor (AhR), 3ʹ,4ʹ-dimethoxyflavone and resveratrol, in vitro and in vivo, respectively. Moreover, the luciferase assays revealed that baicalin significantly increased the luciferase activity of the reporter gene incorporated with the Xenobiotic response elements recognized by AhR. In summary, baicalin significantly reduced the disposition of AAI and ameliorated AAI-induced kidney toxicity through AhR-dependent CYP1A1/2 induction in the liver. PMID:26204831
-
Rapamycin ameliorates IgA nephropathy via cell cycle-dependent mechanisms
Tian, Jihua; Wang, Yanhong; Liu, Xinyan; Zhou, Xiaoshuang
2014-01-01
IgA nephropathy is the most frequent type of glomerulonephritis worldwide. The role of cell cycle regulation in the pathogenesis of IgA nephropathy has been studied. The present study was designed to explore whether rapamycin ameliorates IgA nephropathy via cell cycle-dependent mechanisms. After establishing an IgA nephropathy model, rats were randomly divided into four groups. Coomassie Brilliant Blue was used to measure the 24-h urinary protein levels. Renal function was determined using an autoanalyzer. Proliferation was assayed via Proliferating Cell Nuclear Antigen (PCNA) immunohistochemistry. Rat mesangial cells were cultured and divided into the six groups. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) and flow cytometry were used to detect cell proliferation and the cell cycle phase. Western blotting was performed to determine cyclin E, cyclin-dependent kinase 2, p27Kip1, p70S6K/p-p70S6K, and extracellular signal-regulated kinase 1/2/p- extracellular signal-regulated kinase 1/2 protein expression. A low dose of the mammalian target of rapamycin (mTOR) inhibitor rapamycin prevented an additional increase in proteinuria, protected kidney function, and reduced IgA deposition in a model of IgA nephropathy. Rapamycin inhibited mesangial cell proliferation and arrested the cell cycle in the G1 phase. Rapamycin did not affect the expression of cyclin E and cyclin-dependent kinase 2. However, rapamycin upregulated p27Kip1 at least in part via AKT (also known as protein kinase B)/mTOR. In conclusion, rapamycin can affect cell cycle regulation to inhibit mesangial cell proliferation, thereby reduce IgA deposition, and slow the progression of IgAN. PMID:25349217
-
Mirabal, Sheyla; Varljen, Tatjana; Gayden, Tenzin; Regueiro, Maria; Vujovic, Slavica; Popovic, Danica; Djuric, Marija; Stojkovic, Oliver; Herrera, Rene J
2010-07-01
Southeastern Europe and, particularly, the Balkan Peninsula are especially useful when studying the mechanisms responsible for generating the current distribution of Paleolithic and Neolithic genetic signals observed throughout Europe. In this study, 404 individuals from Montenegro and 179 individuals from Serbia were typed for 17 Y-STR loci and compared across 9 Y-STR loci to geographically targeted previously published collections to ascertain the phylogenetic relationships of populations within the Balkan Peninsula and beyond. We aim to provide information on whether groups in the region represent an amalgamation of Paleolithic and Neolithic genetic substrata, or whether acculturation has played a critical role in the spread of agriculture. We have found genetic markers of Middle Eastern, south Asian and European descent in the area, however, admixture analyses indicate that over 80% of the Balkan gene pool is of European descent. Altogether, our data support the view that the diffusion of agriculture into the Balkan region was mostly a cultural phenomenon although some genetic infiltration from Africa, the Levant, the Caucasus, and the Near East has occurred. (c) 2010 Wiley-Liss, Inc.
-
Overexpression of Mafb in Podocytes Protects against Diabetic Nephropathy
Yoh, Keigyou; Ojima, Masami; Okamura, Midori; Nakamura, Megumi; Hamada, Michito; Shimohata, Homare; Moriguchi, Takashi; Yamagata, Kunihiro; Takahashi, Satoru
2014-01-01
We previously showed that the transcription factor Mafb is essential for podocyte differentiation and foot process formation. Podocytes are susceptible to injury in diabetes, and this injury leads to progression of diabetic nephropathy. In this study, we generated transgenic mice that overexpress Mafb in podocytes using the nephrin promoter/enhancer. To examine a potential pathogenetic role for Mafb in diabetic nephropathy, Mafb transgenic mice were treated with either streptozotocin or saline solution. Diabetic nephropathy was assessed by renal histology and biochemical analyses of urine and serum. Podocyte-specific overexpression of Mafb had no effect on body weight or blood glucose levels in either diabetic or control mice. Notably, albuminuria and changes in BUN levels and renal histology observed in diabetic wild-type animals were ameliorated in diabetic Mafb transgenic mice. Moreover, hyperglycemia-induced downregulation of Nephrin was mitigated in diabetic Mafb transgenic mice, and reporter assay results suggested that Mafb regulates Nephrin directly. Mafb transgenic glomeruli also overexpressed glutathione peroxidase, an antioxidative stress enzyme, and levels of the oxidative stress marker 8-hydroxydeoxyguanosine decreased in the urine of diabetic Mafb transgenic mice. Finally, Notch2 expression increased in diabetic glomeruli, and this effect was enhanced in diabetic Mafb transgenic glomeruli. These data indicate Mafb has a protective role in diabetic nephropathy through regulation of slit diaphragm proteins, antioxidative enzymes, and Notch pathways in podocytes and suggest that Mafb could be a therapeutic target. PMID:24722438
-
Overexpression of Mafb in podocytes protects against diabetic nephropathy.
Morito, Naoki; Yoh, Keigyou; Ojima, Masami; Okamura, Midori; Nakamura, Megumi; Hamada, Michito; Shimohata, Homare; Moriguchi, Takashi; Yamagata, Kunihiro; Takahashi, Satoru
2014-11-01
We previously showed that the transcription factor Mafb is essential for podocyte differentiation and foot process formation. Podocytes are susceptible to injury in diabetes, and this injury leads to progression of diabetic nephropathy. In this study, we generated transgenic mice that overexpress Mafb in podocytes using the nephrin promoter/enhancer. To examine a potential pathogenetic role for Mafb in diabetic nephropathy, Mafb transgenic mice were treated with either streptozotocin or saline solution. Diabetic nephropathy was assessed by renal histology and biochemical analyses of urine and serum. Podocyte-specific overexpression of Mafb had no effect on body weight or blood glucose levels in either diabetic or control mice. Notably, albuminuria and changes in BUN levels and renal histology observed in diabetic wild-type animals were ameliorated in diabetic Mafb transgenic mice. Moreover, hyperglycemia-induced downregulation of Nephrin was mitigated in diabetic Mafb transgenic mice, and reporter assay results suggested that Mafb regulates Nephrin directly. Mafb transgenic glomeruli also overexpressed glutathione peroxidase, an antioxidative stress enzyme, and levels of the oxidative stress marker 8-hydroxydeoxyguanosine decreased in the urine of diabetic Mafb transgenic mice. Finally, Notch2 expression increased in diabetic glomeruli, and this effect was enhanced in diabetic Mafb transgenic glomeruli. These data indicate Mafb has a protective role in diabetic nephropathy through regulation of slit diaphragm proteins, antioxidative enzymes, and Notch pathways in podocytes and suggest that Mafb could be a therapeutic target. Copyright © 2014 by the American Society of Nephrology.
-
Sirolimus damages podocytes in rats with protein overload nephropathy.
Cai, Yong; Chen, Yan; Zheng, Shaoling; Chen, Bicheng; Yang, Yirong; Xia, Peng
2011-01-01
Conversion from calcineurin inhibitors (CNIs) to sirolimus could significantly improve long-term graft survival after kidney transplantation. Proteinuria was found in some recipients after the switch, which could be alleviated by an angiotensin II receptor blocker (ARB). But the mechanisms for this have remained unclear. In this study, we utilized a rat model with protein overload nephropathy to explore the mechanisms of sirolimus-related proteinuria. A rat model with protein overload nephropathy was induced by repeated injections of bovine serum albumin. Model rats also received sirolimus (rapamycin) treatment or ARB agent (losartan) pretreatment. Urinary protein excretion from 24-hour urine specimens was calculated, and the morphological changes of renal tissues were analyzed by hematoxylin and eosin staining and electron microscopy. The expression of desmin, a sensitive marker of podocyte injury, was detected by immunohistochemical staining. Rapamycin increased urinary protein excretion and intratubular protein cast formation in rats with protein overload nephropathy. The foot process effacement of podocytes was found by electron microscopy after rapamycin treatment. The expression of desmin was up-regulated after rapamycin treatment. However, losartan pretreatment could attenuate proteinuria in spite of rapamycin treatment. Sirolimus aggravates proteinuria in rats with protein overload nephropathy by damaging podocytes, a barrier of glomerular filtration. Furthermore, angiotensin II receptor blocker can counteract the effect of sirolimus, not only through hemodynamic changes but also partly by repairing the injury of podocytes. This study might be useful for understanding the mechanism of sirolimus-related proteinuria and guiding clinical treatments.
-
2016-01-01
The Central Balkans region is of great importance for understanding the spread of the Neolithic in Europe but the Early Neolithic population dynamics of the region is unknown. In this study we apply the method of summed calibrated probability distributions to a set of published radiocarbon dates from the Republic of Serbia in order to reconstruct population dynamics in the Early Neolithic in this part of the Central Balkans. The results indicate that there was a significant population growth after ~6200 calBC, when the Neolithic was introduced into the region, followed by a bust at the end of the Early Neolithic phase (~5400 calBC). These results are broadly consistent with the predictions of the Neolithic Demographic Transition theory and the patterns of population booms and busts detected in other regions of Europe. These results suggest that the cultural process that underlies the patterns observed in Central and Western Europe was also in operation in the Central Balkan Neolithic and that the population increase component of this process can be considered as an important factor for the spread of the Neolithic as envisioned in the demic diffusion hypothesis. PMID:27508413
-
IgM nephropathy; can we still ignore it
Vanikar, Aruna
2013-01-01
Context:IgM nephropathy (IgMN) is a relatively less recognized clinico-immunopathological entity in the domain of glomerulonephritis , often thought to be a bridge between minimal change disease and focal segmental glomerulosclerosis. Evidence Acquisitions: Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science has been searched. Results: IgM nephropathy can present as nephritic syndrome or less commonly with subnephrotic proteinuria or rarely hematuria. About 30% patients respond to steroids whereas others are steroid dependent / resistant. They should be given a trial of Rituximab or stem cell therapy. Conclusions:IgM nephropathy (IgMN) is an important and rather neglected pathology responsible for renal morbidity in children and adults in developing countries as compared to developed nations with incidence of 2-18.5% of native biopsies. Abnormal T-cell function with hyperfunctioning suppressor T-cells are believed to be responsible for this disease entity. Approximately one third of the patients are steroid responders where as the remaining two thirds are steroid resistant or dependent. Therapeutic trials including cell therapies targeting suppressor T-cells are required. PMID:24475434
-
A Glimpse of Matrix Metalloproteinases in Diabetic Nephropathy
Xu, X.; Xiao, L.; Xiao, P.; Yang, S.; Chen, G.; Liu, F.; Kanwar, Y.Y.; Sun, L.
2014-01-01
Matrix metalloproteinases (MMPs) are proteolytic enzymes belonging to the family of zinc-dependent endopeptidases that are capable of degrading almost all the proteinaceous components of the extracellular matrix (ECM). It is known that MMPs play a role in a number of renal diseases, such as, various forms of glomerulonephritis and tubular diseases, including some of the inherited kidney diseases. In this regard, ECM accumulation is considered to be a hallmark morphologic finding of diabetic nephropathy, which not only is related to the excessive synthesis of matrix proteins, but also to their decreased degradation by the MMPs. In recent years, increasing evidence suggest that there is a good correlation between the activity or expression of MMPs and progression of renal disease in patients with diabetic nephropathy in humans and in various experimental animal models. In such a diabetic milieu, the expression of MMPs is modulated by high glucose, advanced glycation end products (AGEs), TGF-β, reactive oxygen species (ROS), transcription factors and some of the microRNAs. In this review, we focused on the structure and functions of MMPs, and their role in the pathogenesis of diabetic nephropathy. PMID:25039784
-
Dental calculus reveals Mesolithic foragers in the Balkans consumed domesticated plant foods
Cristiani, Emanuela; Radini, Anita; Edinborough, Marija; Borić, Dušan
2016-01-01
Researchers agree that domesticated plants were introduced into southeast Europe from southwest Asia as a part of a Neolithic “package,” which included domesticated animals and artifacts typical of farming communities. It is commonly believed that this package reached inland areas of the Balkans by ∼6200 calibrated (cal.) BC or later. Our analysis of the starch record entrapped in dental calculus of Mesolithic human teeth at the site of Vlasac in the Danube Gorges of the central Balkans provides direct evidence that already by ∼6600 cal. BC, if not earlier, Late Mesolithic foragers of this region consumed domestic cereals, such as Triticum monococcum, Triticum dicoccum, and Hordeum distichon, which were also the main crops found among Early Neolithic communities of southeast Europe. We infer that “exotic” Neolithic domesticated plants were introduced to southern Europe independently almost half a millennium earlier than previously thought, through networks that enabled exchanges between inland Mesolithic foragers and early farming groups found along the Aegean coast of Turkey. PMID:27573829
-
Patterns of Abundance and Host Specificity of Bat Ectoparasites in the Central Balkans.
Burazerovic, J; Orlova, M; Obradovic, M; Cirovic, D; Tomanovic, S
2018-01-10
Bats are hosts to a number of ectoparasites-acarines (ticks, chiggers, other mites), bat flies, and fleas. Bat ectoparasites might have significant ecological and public health importance as they may be potential vectors of zoonotic agents. It is important to identify their distribution, diversity, and host-parasite associations. Bat ectoparasites in the central Balkans have been largely understudied. The present research was conducted in 45 localities at the territory of Bosnia and Herzegovina, former Yugoslav Republic of Macedonia, Montenegro, and Serbia. In total, 1,143 individuals of 18 species of bats have been examined for the presence and abundance of ectoparasite species during 3 yr of research. In total, 21 ectoparasite species have been identified: three species of ticks, seven species of mites (including one species of chigger), eight species of bat flies, and three species of fleas. In total, 80 host-parasite associations have been identified. The largest number of ectoparasites parasitized primarily only one host species. The highest total number of hosts was identified for ectoparasite species Ixodes vespertilionis Koch, Nycteribia schmidlii Schiner, and Spinturnix myoti Kolenati. The spinturnicid mite Spinturnix psi Kolenati was the most abundant ectoparasite species and together with Penicilidia dufouri Westwood the most widely distributed species of bat ectoparasite, being present at 21 localities in the central Balkans. The presented data include the first systematic records of patterns of prevalence, mean intensity, mean abundance, and host specificity for bat ectoparasites in the central Balkans. © The Author(s) 2017. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
-
Anti-Inflammatory Action of Sitagliptin and Linagliptin in Doxorubicin Nephropathy.
Jo, Chor Ho; Kim, Sua; Park, Joon-Sung; Kim, Gheun-Ho
2018-06-15
Dipeptidyl peptidase-4 (DPP4) inhibitors are known to have a protective effect on diabetic kidney disease, possibly via reduction of oxidative stress and inflammation in the kidney. However, whether these potential mechanisms play a role in non-diabetic proteinuric kidney diseases is not clear. Two different animal experiments were carried out using sitagliptin and linagliptin for DPP4 inhibition. In each experiment, male Sprague-Dawley rats were uninephrectomized and randomly divided into vehicle-treated and doxorubicin-treated rats, with or without DPP4 inhibition. Administration of a DPP4 inhibitor was performed daily by oral gavage over six weeks. A single intravenous injection of doxorubicin resulted in hypertension and remarkable proteinuria. Linagliptin, but not sitagliptin, lowered systolic blood pressure in rats with doxorubicin nephropathy. By contrast, sitagliptin ameliorated tubulointerstitial injury, inflammatory cell infiltration, and interstitial fibrosis in rat kidneys with doxorubicin nephropathy. Quantitative polymerase chain reaction analysis revealed that mRNA expression of NLRP3, caspase-1, ASC, and IL-1β was remarkably increased in rat kidneys with doxorubicin nephropathy, and that this upregulation of the major components of the NLRP3 inflammasome was effectively suppressed by treatment with either sitagliptin or linagliptin. Additionally, upregulation of IL-6 was reversed by linagliptin, but not by sitagliptin. On the other hand, sitagliptin, but not linagliptin, reversed the increase in mRNA expression of gp91phox, p47phox, and p67phox in rat kidneys with doxorubicin nephropathy. NLRP3 inflammasome activation was shown in our rat model of doxorubicin nephropathy. DPP4 inhibitors can suppress the activity of NLRP3, with or without relieving NADPH oxidase 2-related oxidative stress. © 2018 The Author(s). Published by S. Karger AG, Basel.
-
Chronic nephropathies of cocaine and heroin abuse: a critical review.
Jaffe, Jared A; Kimmel, Paul L
2006-07-01
Renal disease in cocaine and heroin users is associated with the nephrotic syndrome, acute glomerulonephritis, amyloidosis, interstitial nephritis, and rhabdomyolysis. The pathophysiologic basis of cocaine-related renal injury involves renal hemodynamic changes, glomerular matrix synthesis and degradation, and oxidative stress and induction of renal atherogenesis. Heroin is the most commonly abused opiate in the United States. Previous studies identified a spectrum of renal diseases in heroin users. The predominant renal lesion in black heroin users is focal segmental glomerulosclerosis and in white heroin users is membranoproliferative glomerulonephritis. Although the prevalence of heroin use in the United States has increased, the incidence of "heroin nephropathy" has declined. Because reports of heroin nephropathy predated the surveillance of hepatitis C virus and HIV, the varied findings might be related to the spectrum of viral illnesses that are encountered in injection drug users. Socioeconomic conditions, cultural and behavioral practices, or differences in genetic susceptibilities may be more associated with the development of nephropathy in heroin users than the drug's pharmacologic properties. Administration of cocaine in animal models results in nonspecific glomerular, interstitial, and tubular cell lesions, but there is no animal model of heroin-associated renal disease. The heterogeneity of responses that are associated with heroin is not consistent with a single or simple notion of nephropathogenesis. There are no well-designed, prospective, epidemiologic studies to assess the incidence and the prevalence of renal disease in populations of opiate users and to establish the validity of a syndrome such as heroin nephropathy. It is concluded although there is a paucity of evidence to support a heroin-associated nephropathy, the evidence from in vitro cellular and animal studies to support the existence of cocaine-induced renal changes is more convincing.
-
Rapamycin ameliorates IgA nephropathy via cell cycle-dependent mechanisms.
Tian, Jihua; Wang, Yanhong; Liu, Xinyan; Zhou, Xiaoshuang; Li, Rongshan
2015-07-01
IgA nephropathy is the most frequent type of glomerulonephritis worldwide. The role of cell cycle regulation in the pathogenesis of IgA nephropathy has been studied. The present study was designed to explore whether rapamycin ameliorates IgA nephropathy via cell cycle-dependent mechanisms. After establishing an IgA nephropathy model, rats were randomly divided into four groups. Coomassie Brilliant Blue was used to measure the 24-h urinary protein levels. Renal function was determined using an autoanalyzer. Proliferation was assayed via Proliferating Cell Nuclear Antigen (PCNA) immunohistochemistry. Rat mesangial cells were cultured and divided into the six groups. Methylthiazolyldiphenyl-tetrazolium bromide (MTT) and flow cytometry were used to detect cell proliferation and the cell cycle phase. Western blotting was performed to determine cyclin E, cyclin-dependent kinase 2, p27(Kip1), p70S6K/p-p70S6K, and extracellular signal-regulated kinase 1/2/p- extracellular signal-regulated kinase 1/2 protein expression. A low dose of the mammalian target of rapamycin (mTOR) inhibitor rapamycin prevented an additional increase in proteinuria, protected kidney function, and reduced IgA deposition in a model of IgA nephropathy. Rapamycin inhibited mesangial cell proliferation and arrested the cell cycle in the G1 phase. Rapamycin did not affect the expression of cyclin E and cyclin-dependent kinase 2. However, rapamycin upregulated p27(Kip1) at least in part via AKT (also known as protein kinase B)/mTOR. In conclusion, rapamycin can affect cell cycle regulation to inhibit mesangial cell proliferation, thereby reduce IgA deposition, and slow the progression of IgAN. © 2014 by the Society for Experimental Biology and Medicine.
-
[Medical and dietetic management of congenital and inherited nephropathies (author's transl)].
Canonaco, F; Guerra, A; Chiossi, C; Cappellini, T; Angeli, G
1981-01-01
The management of the congenital and inherited nephropathies is, still today, almost exclusively symptomatic. The authors relate the most important drugs and the dose used for the principal complications of these nephropathies: hypertension, hypo-dysprotidoemia, oedema, anemia, metabolic acidosis, polyuria, hypoevolutism, recurrent urinary infections. Particular care must be taken in order to provide an adequate caloric-protein allowance principally when the renal insufficiency is reached.
-
The "1+1:Life & Love" Simultaneous Exhibition: Cross-Border Collaboration in the Western Balkans
ERIC Educational Resources Information Center
Walters, Diana
2012-01-01
This article describes and analyzes a cross-border, "simultaneous exhibition" collaborative project in six post-conflict western Balkan countries. Through a process of collaboration, active learning, and audience development, professional and personal trust developed among eleven museums. Previously identified barriers were overcome and…
-
Potassium handling with dual renin-angiotensin system inhibition in diabetic nephropathy.
Van Buren, Peter N; Adams-Huet, Beverley; Nguyen, Mark; Molina, Christopher; Toto, Robert D
2014-02-01
Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are the cornerstones of pharmacologic therapy in diabetic nephropathy. Mineralocorticoid receptor blockers reduce proteinuria as single agents or add-on therapy to other renin-angiotensin-aldosterone system-inhibiting drugs in these patients. The long-term benefits and ultimate role of mineralocorticoid receptor blockers in diabetic nephropathy remain unknown. A clinical trial previously showed that the kalemic effect of spironolactone is higher than losartan when added to lisinopril in patients with diabetic nephropathy. The purpose of this study was to investigate if renal potassium handling was primarily responsible for that observation. In a blinded, randomized, three-arm placebo-controlled clinical trial, 80 participants with diabetic nephropathy taking lisinopril (80 mg) were randomized to spironolactone (25 mg daily), losartan (100 mg daily), or placebo (trial dates from July of 2003 to December of 2006). Serum potassium, aldosterone, and 24-hour urine sodium, potassium, and creatinine were measured over 48 weeks. Differences were analyzed with repeated measures mixed models. Mean follow-up serum potassium was 5.0 mEq/L for spironolactone, 4.7 mEq/L for losartan (P=0.05 versus spironolactone), and 4.5 mEq/L for placebo (P<0.001 versus spironolactone; P=0.03 versus losartan). The difference in serum potassium was 0.23 mEq/L for losartan versus placebo (P=0.02), 0.43 mEq/L for spironolactone versus placebo (P<0.001), and 0.2 mEq/L for spironolactone versus losartan (P=0.05). Serum and urine potassium excretion and secretion rates were similar between groups throughout the study. Spironolactone raised serum potassium more than losartan in patients with diabetic nephropathy receiving lisinopril, despite similar renal sodium and potassium excretion. This finding suggests that extrarenal potassium homeostasis contributes to hyperkalemia in these patients. A better understanding of
-
Is Collapsing C1q Nephropathy Another MYH9-Associated Kidney Disease? A Case Report
Reeves-Daniel, Amber M.; Iskandar, Samy S.; Bowden, Donald W.; Bostrom, Meredith A.; Hicks, Pamela J.; Comeau, Mary E.; Langefeld, Carl D.; Freedman, Barry I.
2009-01-01
C1q nephropathy is a rare kidney disease that can present with nephrotic syndrome and typically has the histological phenotype of either minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). Disagreement exists as to whether it is a distinct immune complex-mediated glomerulopathy or whether it resides in the spectrum of FSGS-MCD. Two African American patients with C1q nephropathy histologically presenting as the collapsing variant of FSGS (collapsing C1q nephropathy) and rapid loss of kidney function were genotyped for polymorphisms in the non-muscle myosin heavy chain 9 gene (MYH9). Both cases were homozygous for the MYH9 E1 risk haplotype; the variant strongly associated with idiopathic FSGS, collapsing FSGS in Human Immunodeficiency Virus-associated nephropathy and focal global glomerulosclerosis (historically attributed to hypertensive nephrosclerosis). Collapsing C1q nephropathy with rapid progression to ESRD appears to reside in the MYH9-associated disease spectrum. PMID:20116156
-
Teachers for the Future: Teacher Development for Inclusive Education in the Western Balkans
ERIC Educational Resources Information Center
Pantic, Natasa; Closs, Alison; Ivosevic, Vanja
2011-01-01
Teachers for the Future is a regional report that draws together and analyses research findings from a study commissioned by the European Training Foundation (ETF) in seven countries in the Western Balkan region, namely Albania, Bosnia and Herzegovina, Croatia, the former Yugoslav Republic of Macedonia, Kosovo, Montenegro and Serbia. The overall…
-
Teachers for the Future: Teacher Development for Inclusive Education in the Western Balkans
ERIC Educational Resources Information Center
Pantic, Natasa; Closs, Alison; Ivosevic, Vanja
2011-01-01
Teachers for the Future is a regional report that draws together and analyses research findings from a study commissioned by the European Training Foundation (ETF) in seven countries in the Western Balkans region, namely, Albania, Bosnia and Herzegovina, Croatia, the former Yugoslav Republic of Macedonia, Kosovo, Montenegro and Serbia. The overall…
-
2011-12-01
conquest of the Balkans and failed siege of Vienna, they considered the Balkans as a new border between their states and Islam and thus a lost cause for...security environment, globalization facilitated the rise of terrorism and unified religious fanatics in their irrational cause . Throughout history...Western World: “The freedom given to these individuals to disseminate propaganda and to rally for the cause among Muslim communities in Europe
-
Wang, Yuxuan; Wang, Chengcheng; Zhang, Xiuli; Gu, Harvest F; Wu, Liang
2018-01-01
Diabetic nephropathy is characterized by hypertension, progressive albuminuria, glomerulosclerosis and declines in glomerular filtration rate leading to end stage renal disease. Although the pathogenesis of diabetic nephropathy is not fully understood, current treatment of the patients with diabetic nephropathy is mainly based upon the control of hyperglycaemia and management of blood pressures. Several drugs, which are originally developed for hypertension therapy, have been adopted for stabilization of renal function in diabetic nephropathy. In this review, we first discussed the relationships between diabetic nephropathy and hypertension particularly in the renin-angiotensinaldosterone system. We then summarized chemical structures, pharmacological characteristics and clinical studies of the common drugs used for treatment of diabetic nephropathy, while these drugs have effects against hypertension. This review may provide the constructive information for further drug development in diabetic nephropathy. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
-
Elmas, Onur; Erbas, Oytun; Yigitturk, Gurkan
2016-10-01
Cytokines, such as transforming growth factor (TGF)-ß1, and increased oxidative stress are considered to be responsible for the development of diabetic nephropathy. We hypothesized that Aesculus hippocastanum (AH) seeds may have preventive effects on oxidative stress and TGF-β-related diabetic nephropathy in streptozotocin (STZ)-induced diabetic nephropathy in rats. Twenty-one male Sprague-Dawley albino rats were divided into three groups (n=7). Except for the control group, they all had diabetic nephropathy induced by an intraperitoneal injection of STZ. While the diabetes group did not receive any medication, the diabetes+AH group was given the medication for 4 weeks. After the experiment, analyses were performed to evaluate the glomerular area, severity of sclerosis, and fibronectin immunoexpression, as well as levels of malondialdehyde (MDA), TGF-β, blood urea nitrogen (BUN), blood glucose, creatinine, and proteinuria. It was found that glomerular area, severity of sclerosis, fibronectin immunoexpression, and levels of MDA, TGF-β, BUN, creatinine, and proteinuria were decreased in the diabetes+AH group. It is known that diabetic nephropathy is induced, to a large extent, by hyperglycemia. In the present study, AH extract ameliorated diabetic nephropathy without decrease in blood glucose levels. In the study, AH seeds showed beneficial effects on the functional properties of the kidney and microscopic improvements in diabetic nephropathy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.
-
Safety and efficacy of enzyme replacement therapy in the nephropathy of Fabry disease
Fervenza, Fernando C; Torra, Roser; Warnock, David G
2008-01-01
Kidney involvement with progressive loss of kidney function (Fabry nephropathy) is an important complication of Fabry disease, an X-linked lysosomal storage disorder arising from deficiency of α-galactosidase activity. Clinical trials have shown that enzyme replacement therapy (ERT) with recombinant human α-galactosidase clears globotriaosylceramide from kidney cells, and can stabilize kidney function in patients with mild to moderate Fabry nephropathy. Recent trials show that patients with more advanced Fabry nephropathy and overt proteinuria do not respond as well to ERT alone, but can benefit from anti-proteinuric therapy given in conjunction with ERT. This review focuses on the use of enzyme replacement therapy with agalsidase-alfa and agalsidase-beta in adults with Fabry nephropathy. The current results are reviewed and evaluated. The issues of dosing of enzyme replacement therapy, the use of adjunctive agents to control urinary protein excretion, and the individual factors that affect disease severity are reviewed. PMID:19707461
-
Kocasarac, Can; Yigit, Yavuz; Sengul, Erkan; Sakalar, Yildirim Beyazit
2018-04-01
To assess changes in choroidal thickness (CT) in diabetes patients with and without diabetic nephropathy using enhanced depth imaging spectral domain optical coherence tomography (EDI-OCT). Thirty-five type 2 diabetes patients with a diagnosis of diabetic nephropathy (DNP) in nephrology department and 35 type 2 diabetes patients without nephropathy (non-DNP) were included in our prospective study consecutively. The control group comprised 34 healthy individuals. CT measurements were recorded under the fovea and at 1500 µm from the foveal center in the nasal and temporal sides. The study parameters also included age, refractive error, axial length, intraocular pressure, HbA1c, glomerular filtration rate and proteinuria amount. The subfoveal, temporal and nasal choroidal thickness was noted to be thinner in patients with DNP compared with non-DNP and normal subjects (p < 0.05). However, CT measurements did not show any difference between the healthy and non-DNP group. CT decreases significantly in diabetic patients when diabetic nephropathy accompanies diabetes mellitus.
-
A clinicopathological study of C1q nephropathy at King Abdulaziz University.
Mokhtar, Ghadeer A; Jalalah, Sawsan M
2015-07-01
C1q nephropathy is a relatively rare idiopathic glomerulopathy characterized by mesangial immunoglobulin and complement deposits with dominance or co-dominance of C1q, with no evidence of systemic lupus erythematosus. We describe the incidence, clinical manifestation, histopathological features, and follow-up of patients with C1q nephropathy at our institute. Of 750 kidney biopsy specimens obtained in the period of January 2000 to December 2011, all the cases that meet the criteria for the diagnosis of C1q nephropathy were retrieved. The histological slides were examined and the clinical charts were reviewed by 2renal pathologists. We had 11 patients, all children, that met the criteria for the diagnosis of C1q nephropathy accounting for an incidence of 1.5%. The mean age at the time of presentation was 3.7 years and all the patients were presented with nephrotic syndrome. Two patients had microhematuria and 2 had hypertension. Histological examination of these cases showed variable degrees of mesangial cells hypercellularity and matrix expansion with focal segmental glomerulosclerosis observed in 2 cases. Nine patients were steroid resistant (82%) and 2 were steroid dependent. Six patients required immunosuppressive therapy and 1 patient developed end-stage renal disease. In our series, C1q nephropathy affected predominantly young children. Mesangioproliferative pattern was the most frequent histopathological finding in these patients. Clinically, despite steroid resistance, the patients had a relatively good outcome; the worst prognostic outcome was associated with collapsing glomerulopathy.
-
Histone deacetylase 4 selectively contributes to podocyte injury in diabetic nephropathy.
Wang, Xiaojie; Liu, Jiang; Zhen, Junhui; Zhang, Chun; Wan, Qiang; Liu, Guangyi; Wei, Xinbing; Zhang, Yan; Wang, Ziying; Han, Huirong; Xu, Huiyan; Bao, Chanchan; Song, Zhenyu; Zhang, Xiumei; Li, Ningjun; Yi, Fan
2014-10-01
Studies have highlighted the importance of histone deacetylase (HDAC)-mediated epigenetic processes in the development of diabetic complications. Inhibitors of HDAC are a novel class of therapeutic agents in diabetic nephropathy, but currently available inhibitors are mostly nonselective inhibit multiple HDACs, and different HDACs serve very distinct functions. Therefore, it is essential to determine the role of individual HDACs in diabetic nephropathy and develop HDAC inhibitors with improved specificity. First, we identified the expression patterns of HDACs and found that, among zinc-dependent HDACs, HDAC2/4/5 were upregulated in the kidney from streptozotocin-induced diabetic rats, diabetic db/db mice, and in kidney biopsies from diabetic patients. Podocytes treated with high glucose, advanced glycation end products, or transforming growth factor-β (common detrimental factors in diabetic nephropathy) selectively increased HDAC4 expression. The role of HDAC4 was evaluated by in vivo gene silencing by intrarenal lentiviral gene delivery and found to reduce renal injury in diabetic rats. Podocyte injury was associated with suppressing autophagy and exacerbating inflammation by HDAC4-STAT1 signaling in vitro. Thus, HDAC4 contributes to podocyte injury and is one of critical components of a signal transduction pathway that links renal injury to autophagy in diabetic nephropathy.
-
[Chronic transplant nephropathy].
Campistol Plana, J M
2008-01-01
In 2007 there were important scientific contributions in the field of kidney transplant and specifically in chronic transplant nephropathy (interstitial fibrosis and tubular atrophy). A new nomenclature and classification of chronic kidney disease was probably the most important contribution in this entity. Use of the C4d stain has allowed the concepts of glomerulopathy to be updated and to reveal the frequency of this entity and its impact in kidney transplant. Finally, two experimental studies provide new perspectives on the treatment of chronic kidney disease such as the use of statins or the use of pyridoxamine to block glycation end products.
-
Bautista, Josef Edrik Keith; Merhi, Basma; Gregory, Oliver; Hu, Susie; Henriksen, Kammi; Gohh, Reginald
2015-01-01
In this paper we present an interesting case of acute kidney injury and severe metabolic alkalosis in a patient with a history of heavy heroin abuse. Urine microscopy showed numerous broomstick-like crystals. These crystals are also identified in light and electron microscopy. We hypothesize that heroin crystalizes in an alkaline pH, resulting in tubular obstruction and acute kidney injury. Management is mainly supportive as there is no known specific therapy for this condition. This paper highlights the utility of urine microscopy in diagnosing the etiology of acute kidney injury and proposes a novel disease called heroin crystal nephropathy. PMID:26034599
-
Mardon, Julie; Thiel, Elise; Laniau, Martine; Sijtsema, Siet; Zimmermann, Karin; Barjolle, Dominique
2015-07-01
This study aims to identify subgroups of consumers based on the health motives underlying their food choice in Western Balkan Countries. The survey (n = 2943) was based on the Food Choice Questionnaire (FCQ) and elicited information on socio-demographic characteristics, consumption frequency of healthy food products, nutrition knowledge and impulsiveness. Analysis of the FCQ data focused on items of "health and natural content" and "weight control" factors to identify clusters. The biggest group of the sample was weight control and health-concerned individuals (34 %), mainly urban women older than 50. The second group of respondents (31 %) was moderately motivated about health and weight. A third group was health concerned but paid less attention to weight control (21 %), mainly comprising men and people living with children. The last group consisted of unconcerned young men (14 %) eating less fruit and showing higher impulsiveness. Western Balkan consumers differ in the importance they attach to health and natural content and weight control. This insight is needed to target interventions.
-
Agenda-Setting for VET Policy in the Western Balkans: Employability versus Social Inclusion
ERIC Educational Resources Information Center
Bartlett, Will; Pagliarello, Marina Cino
2016-01-01
For the last decade, the Western Balkan countries have sought to modernise their vocational education and training (VET) systems, adapting them to the needs of their emerging market economies. Within the framework of the EU accession process, the policy agenda for VET policies has been strongly influenced by a range of international and domestic…
-
McHugh, Kirk M
2014-04-01
Congenital obstructive nephropathy remains one of the leading causes of chronic renal failure in children. The direct link between obstructed urine flow and abnormal renal development and subsequent dysfunction represents a central paradigm of urogenital pathogenesis that has far-reaching clinical implications. Even so, a number of diagnostic, prognostic, and therapeutic quandaries still exist in the management of congenital obstructive nephropathy. Studies in our laboratory have characterized a unique mutant mouse line that develops in utero megabladder, variable hydronephrosis, and progressive renal failure. Megabladder mice represent a valuable functional model for the study of congenital obstructive nephropathy. Recent studies have begun to shed light on the genetic etiology of mgb (-/-) mice as well as the molecular pathways controlling disease progression in these animals.
-
Juniperus phoenicea var. turbinata (Guss.) Parl. Leaf Essential Oil Variability in the Balkans.
Rajčević, Nemanja F; Labus, Marina G; Dodoš, Tanja Z; Novaković, Jelica J; Marin, Petar D
2018-06-15
In the present work leaf essential oil from 97 individuals of Juniperus phoenicea var. turbinata (GUSS.) PARL. from the Balkan Peninsula was analysed. The essential oil was dominated by monoterpene hydrocarbons (45.5 - 71.8%), of which α-pinene was the most abundant in almost all of the samples (38.2 - 55.8%). Several other monoterpenes and sesquiterpenes were also present in relatively high abundances in samples such as myrcene, δ-3-carene, ß-phellandrene, α-terpinyl acetate, (E)-caryophyllene and germacrene D. Multivariate statistical analysis suggested the existence of three possible chemotypes based on the abundance of the four components. Even though the intrapopulation variability was high, discriminant analysis (DA) was able to separate populations. DA showed high separation between western and eastern populations but also grouped geographically closer populations along the west Balkan shoreline. The potential influence of the climate on the composition of the essential oil was also studied. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
-
Gallic acid attenuates type I diabetic nephropathy in rats.
Garud, Mayuresh Sudamrao; Kulkarni, Yogesh Anant
2018-02-25
Literature suggests that TGF-β1 has a central role in the progression of diabetic nephropathy and its down regulation can improve the disease condition. Oxidative stress, generation of advanced glycation end products and activation of renin angiotensin system are the connecting links between hyperglycemia and TGF-β1 over expression. Gallic acid is a phytochemical having wide range of biological activities. Gallic acid is reported to have antioxidant and advanced glycation inhibitory activity. It has also shown inhibitory effects on angiotensin converting enzyme. Gallic acid qualifies as a drug candidate to be tested in the diabetic nephropathy, one of the important complication of diabetes. Streptozotocin (55 mg/kg body weight, i.p.) induced diabetic nephropathy was used as an experimental model. Gallic acid was evaluated for its possible effect at the dose of 20 and 40 mg/kg body weight. Gallic acid treatment significantly lowered plasma levels of the creatinine and blood urea nitrogen and elevated the levels of the protein and albumin. Gallic acid also improved creatinine clearance. Determination of oxidative stress parameters showed that the oxidative stress in kidney tissues was reduced significantly in gallic acid treated animals. Results of the plasma, urine and oxidative stress parameters were also reflected in the histopathological evaluation showing improvement in kidney pathophysiology. ELISA assay for circulating TGF-β1 evaluation and immunohistochemical study for determination of kidney expression of TGF-β1 revealed that gallic acid significantly lowered both the circulating and tissue levels of TGF-β1. Results support the hypothesis that gallic acid can be effectively used in the treatment of diabetic nephropathy. Copyright © 2018 Elsevier B.V. All rights reserved.
-
A Mendelian locus on chromosome 16 determines susceptibility to doxorubicin nephropathy in the mouse
Zheng, Zongyu; Schmidt-Ott, Kai M.; Chua, Streamson; Foster, Kirk A.; Frankel, Rachelle Z.; Pavlidis, Paul; Barasch, Jonathan; D'Agati, Vivette D.; Gharavi, Ali G.
2005-01-01
The development of kidney disease is influenced by both genetic and environmental factors. Searching for models of glomerulopathy that display strong gene–environment interaction, we examined the determinants of anthracycline-induced nephropathy, a classic, strain-dependent experimental model applied to rodents in the past four decades. We produced three crosses derived from mice with contrasting susceptibility to doxorubicin (DOX) nephropathy and, surprisingly, we found that this widely studied model segregates as a single-gene defect with recessive inheritance. By genome-wide analysis of linkage, we mapped the trait locus to chromosome 16A1-B1 (DOXNPH locus) in all three crosses [peak logarithm of odds (lod) score of 92.7, P = 1 × 10-65]; this interval represents a susceptibility locus for nephropathy. Gene expression analysis indicated that susceptibility alleles at the DOXNPH locus are associated with blunted expression of protein arginine methyltransferase 7 (Prmt7) on chromosome 8, a protein previously implicated in cellular sensitivity to chemotherapeutic agents (lod = 12.4, P = 0.0001). Therefore, Prmt7 expression serves as a molecular marker for susceptibility to DOX nephropathy. Finally, increased variation in the severity of kidney disease among affected mice motivated a second genome-wide search, identifying a locus on chromosome 9 that influences the severity and progression of nephropathy (DOXmod, peak lod score 4.3, P = 0.0018). These data provide genetic and molecular characterization of a previously unrecognized Mendelian trait. Elucidation of DOX nephropathy may simultaneously provide insight into the pathogenesis of renal failure and mechanisms of cytotoxicity induced by chemotherapeutic agents. PMID:15699352
-
Zheng, Zongyu; Schmidt-Ott, Kai M; Chua, Streamson; Foster, Kirk A; Frankel, Rachelle Z; Pavlidis, Paul; Barasch, Jonathan; D'Agati, Vivette D; Gharavi, Ali G
2005-02-15
The development of kidney disease is influenced by both genetic and environmental factors. Searching for models of glomerulopathy that display strong gene-environment interaction, we examined the determinants of anthracycline-induced nephropathy, a classic, strain-dependent experimental model applied to rodents in the past four decades. We produced three crosses derived from mice with contrasting susceptibility to doxorubicin (DOX) nephropathy and, surprisingly, we found that this widely studied model segregates as a single-gene defect with recessive inheritance. By genome-wide analysis of linkage, we mapped the trait locus to chromosome 16A1-B1 (DOXNPH locus) in all three crosses [peak logarithm of odds (lod) score of 92.7, P = 1 x 10(-65)]; this interval represents a susceptibility locus for nephropathy. Gene expression analysis indicated that susceptibility alleles at the DOXNPH locus are associated with blunted expression of protein arginine methyltransferase 7 (Prmt7) on chromosome 8, a protein previously implicated in cellular sensitivity to chemotherapeutic agents (lod = 12.4, P = 0.0001). Therefore, Prmt7 expression serves as a molecular marker for susceptibility to DOX nephropathy. Finally, increased variation in the severity of kidney disease among affected mice motivated a second genome-wide search, identifying a locus on chromosome 9 that influences the severity and progression of nephropathy (DOXmod, peak lod score 4.3, P = 0.0018). These data provide genetic and molecular characterization of a previously unrecognized Mendelian trait. Elucidation of DOX nephropathy may simultaneously provide insight into the pathogenesis of renal failure and mechanisms of cytotoxicity induced by chemotherapeutic agents.
-
Tisseuil, Clément; Velo, Enkelejda; Bino, Silvia; Kadriaj, Perparim; Mersini, Kujtim; Shukullari, Ada; Simaku, Artan; Rogozi, Elton; Caputo, Beniamino; Ducheyne, Els; Della Torre, Alessandra; Reiter, Paul; Gilbert, Marius
2018-02-01
The increasing spread of the Asian tiger mosquito, Aedes albopictus, in Europe and US raises public health concern due to the species competence to transmit several exotic human arboviruses, among which dengue, chikungunya and Zika, and urges the development of suitable modeling approach to forecast the spatial and temporal distribution of the mosquito. Here we developed a dynamical species distribution modeling approach forecasting Ae. albopictus eggs abundance at high spatial (0.01 degree WGS84) and temporal (weekly) resolution over 10 Balkan countries, using temperature times series of Modis data products and altitude as input predictors. The model was satisfactorily calibrated and validated over Albania based observed eggs abundance data weekly monitored during three years. For a given week of the year, eggs abundance was mainly predicted by the number of eggs and the mean temperature recorded in the preceding weeks. That is, results are in agreement with the biological cycle of the mosquito, reflecting the effect temperature on eggs spawning, maturation and hatching. The model, seeded by initial egg values derived from a second model, was then used to forecast the spatial and temporal distribution of eggs abundance over the selected Balkan countries, weekly in 2011, 2012 and 2013. The present study is a baseline to develop an easy-handling forecasting model able to provide information useful for promoting active surveillance and possibly prevention of Ae. albopictus colonization in presently non-infested areas in the Balkans as well as in other temperate regions.
-
Acute toxic nephropathies: clinical pathologic correlations.
Muehrcke, R C; Volini, F I; Morris, A M; Moles, J B; Lawrence, A G
1976-01-01
Man's ever increasing exposure to numerous drugs and chemicals, which are the results of medical and industrial progress, produces a by-product of acute toxic nephropathies. These include acute toxic renal failure, drug-induced acute oliguric renal failure, acute hemorrhagic glomerulonephritis, nephrotic syndrome, tubular disturbances and potassium deficiency. In depth information is provided for the previously mentioned disorders.
-
Ivkovic, Ana; Rožić, Anamarija; Turk, Nana
2016-12-01
This is the 20th in a series of articles exploring international trends in health science librarianship in the 21st century. The focus of the present issue is the Balkan region (Serbia and Slovenia). The next regular feature will look at Russia and the Ukraine. JM. © 2016 Health Libraries Group.
-
Diabetic nephropathy. Is end-stage renal disease inevitable?
Bogusky, R T
1983-10-01
The appearance of proteinuria in an insulin-dependent diabetic patient is an ominous sign. Proteinuria heralds the presence of diabetic nephropathy and early death, or chronic renal failure requiring dialysis or transplantation, in 50% of patients. The pathogenesis of diabetic nephropathy is unknown. Adequate insulin administration is the most important preventive measure. Hypertension, if present, should be aggressively treated to delay progression of renal disease. Good nutrition, prompt treatment of urinary tract infections, and caution in the use of radiocontrast agents are other important preventive measures. Hemodialysis, peritoneal dialysis, and transplantation are options for patients with end-stage renal disease. No matter which is selected, the patient may still have multiple amputations, blindness, congestive heart failure, infections, and uncontrolled glycemia. Advancements are being made, however, that promise a better future for insulin-dependent diabetics.
-
Polenakovic, Momir; Nenov, Dimitar; Basci, Ali; Djukanovic, Ljubica; Tsakiris, Dimitris; Nesic, Vida; Schiller, Adalbert; Spasovski, Goce; Klinkmann, Horst; Vienken, Joerg; Falkenhagen, Dieter; Ivanovich, Peter
2013-01-01
The Balkan Cities Association of Nephrology, Dialysis, Transplantation and Artificial Organs (BANTAO) was born in Ohrid on October 9, 1993. The war in former Yugoslavia negatively affected the development of nephrology and also the connections among the nephrologists from the Balkans. However, there was willingness for further mutual collaboration between the nephrologists from the Balkans. The war in Yugoslavia created hate among people, between the newly established countries, and there were problems with the recognition of the names of the new countries, and so, the nephrologists decided to apply the ancient principle of using the names of the cities, instead of the countries, as the founders of the Association. The main goal of BANTAO is to promote scientific and technical cooperation in the fields of renal disease and artificial organs between the regions on the Balkan Peninsula and the world, to give an opportunity for exchange of experience and knowledge among the experts in the area and to engage in collaborative projects in order to demonstrate that cooperation is possible even on the turbulent Balkan Peninsula. The I BANTAO congress was held in Varna from September 22 to 24th, 1995 (President--D. Nenov, Varna). The II congress of BANTAO was held from September 6th to 10th, 1997 in Struga, (President--M. Polenakovic, Skopje). The III BANTAO congress was held in Belgrade from September 18th to 20th, 1998 (President--Lj. Djukanović, Belgrade). The IV congress of BANTAO was held in Izmir from 14th to 16th November 1999 (President--A. Akcicek, Izmir). The V Congress of BANTAO was held in Thessaloniki from September 30th to October 3rd, 2001 (President--P. Stathakis, Athens). The VI Congress of BANTAO was held for the second time in Varna from 6th to 9th October 2003 (President--D. Nenov, Varna). The VII congress of BANTAO was held from September 8th to 11th, 2005 in Ohrid, (President--M. Polenakovic, Skopje). The VIII BANTAO congress was held in Belgrade, 16
-
Immunoglobulin A nephropathy in association with generalized inflammatory peeling skin syndrome.
Srinivasaraghavan, Rangan; Krishnamurthy, Sriram; Chandar, Rumesh; Mahadevan, Subramanian; Chandrashekar, Laxmisha; Rajesh, Nachiappa Ganesh
2015-01-01
We describe an 8-year-old girl born to second-degree consanguineous parents with complaints of recurrent episodes of hematuria for 6 months. She had generalized peeling of the skin since birth and recurrent purulent cutaneous infections. The clinical presentation and histopathology of the skin biopsy specimen were consistent with the inflammatory variant of peeling skin syndrome (PSS). She also had a single ventricle with pulmonary stenosis, for which a bidirectional Glenn shunt had been placed. The renal biopsy specimen showed immunoglobulin A (IgA) nephropathy. She responded well to enalapril and steroids, with a decrease in proteinuria. IgA nephropathy has not been previously reported in PSS. Complications such as IgA nephropathy in children with PSS would help to further delineate the diverse clinical presentations and the clinical course of this rare dermatosis. We discuss the mechanisms that could explain this hitherto unreported association. © 2014 Wiley Periodicals, Inc.
-
Interleukin-20 targets podocytes and is upregulated in experimental murine diabetic nephropathy.
Hsu, Yu-Hsiang; Li, Hsing-Hui; Sung, Junne-Ming; Chen, Wei-Yu; Hou, Ya-Chin; Weng, Yun-Han; Lai, Wei-Ting; Wu, Chih-Hsing; Chang, Ming-Shi
2017-03-31
Interleukin (IL)-20, a proinflammatory cytokine of the IL-10 family, is involved in acute and chronic renal failure. The aim of this study was to elucidate the role of IL-20 during diabetic nephropathy development. We found that IL-20 and its receptor IL-20R1 were upregulated in the kidneys of mice and rats with STZ-induced diabetes. In vitro, IL-20 induced MMP-9, MCP-1, TGF-β1 and VEGF expression in podocytes. IL-20 was upregulated by hydrogen peroxide, high-dose glucose and TGF-β1. In addition, IL-20 induced apoptosis in podocytes by activating caspase-8. In STZ-induced early diabetic nephropathy, IL-20R1-deficient mice had lower blood glucose and serum BUN levels and a smaller glomerular area than did wild-type controls. Anti-IL-20 monoclonal antibody (7E) treatment reduced blood glucose and the glomerular area and improved renal functions in mice in the early stage of STZ-induced diabetic nephropathy. ELISA showed that the serum IL-20 level was higher in patients with diabetes mellitus than in healthy controls. The findings of this study suggest that IL-20 induces cell apoptosis of podocytes and plays a role in the pathogenesis of early diabetic nephropathy.
-
Ha, Sung-Kyu
2014-01-01
Approximately 20–40% of diabetic patients develop nephropathy which is the leading cause of ESRD in developed countries. The ACE I/D polymorphism is thought to be a marker for functional polymorphism which regulates circulating and tissue ACE activity. While the initial study found a protective effect of the II genotype on the development of nephropathy in IDDM patients, subsequent studies have addressed the role of ACE I/D polymorphism in the development and progression of diabetic nephropathy. RAAS blockers are the first line drugs for the treatment hypertension associated with diabetes and have been widely used in everyday clinical practice for the purpose of reducing proteinuria in patients with various renal diseases. However, the antiproteinuric effect of RAAS blockers is variable and the percentage of reducing proteinuria is in the range of 20–80%. The antiproteinuric effect of RAAS blockers may be related to a number of factors: the type or the dose of RAAS blockers, the duration of therapy, the level of sodium intake, and the type of patient's ACE I/D genotype. Besides the nongenetic factors, drug responses, can be influenced by ACE gene polymorphism. In this review, we discuss the relationship between ACE I/D polymorphism and diabetic nephropathy and therapeutic response of RAAS blockers. PMID:25587546
-
Clinical utility of histological features of polyomavirus allograft nephropathy.
Gaber, Lillian W; Egidi, M Francesca; Stratta, Robert J; Lo, Agnes; Moore, Linda W; Gaber, A Osama
2006-07-27
The purpose of this study was to determine if histological features of polyomavirus allograft nephropathy (PVAN) are associated with the clinical presentation and outcomes of PVAN. We examined the histological features of initial and follow-up biopsies of 20 kidney and kidney-pancreas transplant recipients with PVAN during a time prior to routine surveillance. The subjects' demographics, clinical characteristics, and outcomes were compared based upon classification of histological features of PVAN on initial biopsy. Diabetes mellitus (45%) and a history of tacrolimus-induced nephrotoxicity (35%) appeared to be prevalent in subjects with PVAN. Although histological severity of PVAN did not predict or correlate with the clinical course of PVAN, subjects with pattern C on initial PVAN biopsy presented later posttransplant, had higher serum creatinine level at presentation, and had significant allograft deterioration at follow-up than subjects with either pattern A or B on initial biopsy. Resolution of PVAN was noted in 60% of follow-up biopsies and occurred more frequently in subjects with pattern B on initial biopsy. Most subjects developed chronic allograft nephropathy after PVAN and viral clearance did not abrogate the progression to chronic allograft nephropathy. These data indicate that histologic patterns of PVAN may have clinical correlation to disease presentation and prognosis.
-
Bile Cast Nephropathy Caused by Obstructive Cholestasis.
Aniort, Julien; Poyet, Anaïs; Kemeny, Jean-Louis; Philipponnet, Carole; Heng, Anne-Elisabeth
2017-01-01
Acute kidney injury (AKI) is a major complication in patients with liver disease. Although hepatorenal syndrome is frequently involved, bile cast nephropathy, characterized by tubular bile cast formation, has been scarcely described in the setting of severe liver failure. Few renal histology studies are available in these patients. We describe a case of bile cast nephropathy in a patient with obstructive cholestasis caused by stones in the common bile duct. The kidney biopsy confirmed this diagnosis, with several green casts in tubular lumens, tubular injury, and bilirubin composition of the tubular casts with Hall stain. The patient had no confounding cause of kidney failure, and complete kidney recovery followed removal of the bile duct obstruction. This case shows that severe cholestasis is sufficient to cause AKI, and that AKI can be reversible after treatment of the biliary obstruction. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
-
The environmental state of rivers in the Balkans--a review within the DPSIR framework.
Skoulikidis, Nikolaos Th
2009-04-01
Fifteen major Balkan rivers with over 80% of the inflows in Eastern Mediterranean were examined for their environmental state within the DPSIR framework. Physicogeographic and hydrochemical conditions differ substantially among river basins, which may be roughly classified into three main zones. Despite strong fragmentation, most of the rivers are liable to flash floods and have low summer flow. Decreasing precipitation and (mis)management caused a dramatic discharge reduction over the last decades. Wars, political instability, economical crises over the past decades, combined with administrative and structural constraints, poor environmental planning and inspection and, frequently, a lack of environmental awareness imposed significant pressures on rivers. Large wetland areas were drained in favour of widespread intensive agriculture. The treatment of municipal wastewaters is barely adequate in Greece and insufficient elsewhere, while management and treatment of mining and industrial wastewaters is overall poor. In general, lowland river sections are hydro-morphologically modified and are at the greatest pollution risk, while upstream areas mostly retain their natural conditions. Nutrient concentrations in a number of central and eastern Balkan rivers often exceed quality standards, whereas pesticides and heavy metals, partly of geochemical origin, occasionally exceed quality standards. Reservoirs retain vast masses of sediments, thus adversely affecting delta evolution, while dam operation disturbs the seasonal hydrological and hydrochemical regimes. Almost all Balkan countries face daunting water resource challenges because of urgently needed investments in water supply, sanitation, irrigation, and hydroelectricity. International treaties and designations and European Union Directives have mobilized pollution mitigation and conservation efforts. However, the application of environmental legislation has proved in a number of cases inadequate. Constraints arise
-
Al-Raisi, Fatma; Mohsin, Nabil; Kamble, Pramod
2015-04-01
Nephropathy from BK virus (BKV) infection is a growing challenge in kidney transplant recipients globally. It is the result of contemporary potent immunosuppressives aimed at reducing acute rejection and improving allograft survival. Untreated BK virus infections lead to kidney allograft dysfunction or loss. Decreased immunosuppression is the principle treatment but predisposes to acute and chronic rejection. Screening for early detection and prevention of symptomatic BK virus nephropathy may improve outcomes. Although no approved antiviral drug is available, leflunomide, cidofovir, quinolones, and intravenous immunoglobulin have been used. Since the introduction of the new immunosuppressive agents in the transplant regimen at the Royal Hospital, Few cases of BK virus have been detected, and the challenge was to decide upon the best treatment option. The audit was carried out at the Royal Hospital-Oman between January 2010 and December 2012. The nephrology consultant and the clinical pharmacist reviewed all the BK cases and the Royal Hospital. Extensive literature review carried out by the pharmacist to look into the prevalence, prognosis and treatment of BK nephropathy. A treatment protocol was prepared by the clinical pharmacist through guidance of the consultant and was peer reviewed by team of clinical pharmacists and nephrology doctors and approved by the consultant. The audit included 19 patients with positive BK virus ployoma nephropathy. The treatment options were applied stepwise in all the patients with BK virus nephropathy with success rate more than 70%. BK virus nephropathy is emerging at an alarming rate and requires increasing awareness. The uses of current treatment options are still questionable. Our audit confirms that reducing immunosuppression appears to be the criterian standard for the treatment of BK nephropathy.
-
Probabilistic Seismic Risk Model for Western Balkans
NASA Astrophysics Data System (ADS)
Stejskal, Vladimir; Lorenzo, Francisco; Pousse, Guillaume; Radovanovic, Slavica; Pekevski, Lazo; Dojcinovski, Dragi; Lokin, Petar; Petronijevic, Mira; Sipka, Vesna
2010-05-01
A probabilistic seismic risk model for insurance and reinsurance purposes is presented for an area of Western Balkans, covering former Yugoslavia and Albania. This territory experienced many severe earthquakes during past centuries producing significant damage to many population centres in the region. The highest hazard is related to external Dinarides, namely to the collision zone of the Adriatic plate. The model is based on a unified catalogue for the region and a seismic source model consisting of more than 30 zones covering all the three main structural units - Southern Alps, Dinarides and the south-western margin of the Pannonian Basin. A probabilistic methodology using Monte Carlo simulation was applied to generate the hazard component of the model. Unique set of damage functions based on both loss experience and engineering assessments is used to convert the modelled ground motion severity into the monetary loss.
-
Moeller, Sina; Canetta, Pietro A; Taylor, Annette K; Arguelles-Grande, Carolina; Snyder, Holly; Green, Peter H; Kiryluk, Krzysztof; Alaedini, Armin
2014-01-01
IgA nephropathy is the most common form of primary glomerulonephritis worldwide. Mucosal infections and food antigens, including wheat gluten, have been proposed as potential contributing environmental factors. Increased immune reactivity to gluten and/or association with celiac disease, an autoimmune disorder triggered by ingestion of gluten, have been reported in IgA nephropathy. However, studies are inconsistent about this association. We aimed to evaluate the proposed link between IgA nephropathy and celiac disease or immune reactivity to gluten by conducting a comprehensive analysis of associated serologic markers in cohorts of well-characterized patients and controls. Study participants included patients with biopsy-proven IgA nephropathy (n = 99), unaffected controls of similar age, gender, and race (n = 96), and patients with biopsy-proven celiac disease (n = 30). All serum specimens were tested for IgG and IgA antibodies to native gliadin and deamidated gliadin, as well as IgA antibody to transglutaminase 2 (TG2). Anti-TG2 antibody-positive nephropathy patients and unaffected controls were subsequently tested for IgA anti-endomysial antibody and genotyped for celiac disease-associated HLA-DQ2 and -DQ8 alleles. In comparison to unaffected controls, there was not a statistically significant increase in IgA or IgG antibody reactivity to gliadin in individuals with IgA nephropathy. In addition, the levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between IgA nephropathy patients and unaffected controls. Results of the additional anti-endomysial antibody testing and HLA genotyping were corroborative. The data from this case-control study do not reveal any evidence to suggest a significant role for celiac disease or immune reactivity to gluten in IgA nephropathy.
-
Moeller, Sina; Canetta, Pietro A.; Taylor, Annette K.; Arguelles-Grande, Carolina; Snyder, Holly; Green, Peter H.; Kiryluk, Krzysztof; Alaedini, Armin
2014-01-01
IgA nephropathy is the most common form of primary glomerulonephritis worldwide. Mucosal infections and food antigens, including wheat gluten, have been proposed as potential contributing environmental factors. Increased immune reactivity to gluten and/or association with celiac disease, an autoimmune disorder triggered by ingestion of gluten, have been reported in IgA nephropathy. However, studies are inconsistent about this association. We aimed to evaluate the proposed link between IgA nephropathy and celiac disease or immune reactivity to gluten by conducting a comprehensive analysis of associated serologic markers in cohorts of well-characterized patients and controls. Study participants included patients with biopsy-proven IgA nephropathy (n = 99), unaffected controls of similar age, gender, and race (n = 96), and patients with biopsy-proven celiac disease (n = 30). All serum specimens were tested for IgG and IgA antibodies to native gliadin and deamidated gliadin, as well as IgA antibody to transglutaminase 2 (TG2). Anti-TG2 antibody-positive nephropathy patients and unaffected controls were subsequently tested for IgA anti-endomysial antibody and genotyped for celiac disease-associated HLA-DQ2 and -DQ8 alleles. In comparison to unaffected controls, there was not a statistically significant increase in IgA or IgG antibody reactivity to gliadin in individuals with IgA nephropathy. In addition, the levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between IgA nephropathy patients and unaffected controls. Results of the additional anti-endomysial antibody testing and HLA genotyping were corroborative. The data from this case-control study do not reveal any evidence to suggest a significant role for celiac disease or immune reactivity to gluten in IgA nephropathy. PMID:24732864
-
Everett, Charles J; Thompson, Olivia M
2016-06-01
We assessed the association of three chlorinated dibenzo-p-dioxins, a chlorinated dibenzofuran, and four dioxin-like polychlorinated biphenyls (PCBs) in human blood with nephropathy (microalbuminuria or macroalbuminuria) among teens and young adults (12-30 years old) having normal glycohemoglobin (A1c <5.7%). The data were derived from the 1999-2004 National Health and Nutrition Examination Survey (unweighted n=1504, population estimate=38,806,338). In this paper, nephropathy refers to normal A1c with nephropathy. In an all-adult sample (Everett CJ, Thompson OM. Dioxins, furans and dioxin-like PCBs in human blood: causes or consequences of diabetic nephropathy? Environ Res 2014;132:126-31), the cut-offs for these chemicals being considered elevated, were defined as the 75th percentile. Using these same cut-offs again, the proportion of those with one or more of the eight dioxin-like compounds elevated was 9.9%. The four chemicals associated with nephropathy were 1,2,3,6,7,8-hexachlorodibenzo-p-dioxin, PCB 126, PCB 169, and PCB 156. The proportion with one or more of these four dioxin-like chemicals elevated was 3.9% (unweighted n=46) and the odds ratio (OR) for nephropathy was 7.1 [95% confidence interval (CI) 1.8-28.1]. The association was strong among females (OR 17.4, 95% CI 3.4-88.6), but among males there were no cases of nephropathy when one or more of the four dioxin-like chemicals were elevated, and therefore no association. In a separate analysis, elevated toxic equivalency, defined using the eight dioxin-like chemicals (TEQ8), was associated with nephropathy. TEQ8 ≥50.12 fg/g included 2.6% of the sample (unweighted n=28) and had an OR of 5.8 (95% 1.3-25.9) for nephropathy. As found in the analysis of one or more of four dioxin-like chemicals elevated, TEQ8 ≥50.12 fg/g was associated with nephropathy among females (OR 11.9, 95% CI 1.6-87.2), but not males. Trends for least-squares means also differed by gender, but there were no significant differences
-
Valade, R; Kenis, M; Hernandez-Lopez, A; Augustin, S; Mari Mena, N; Magnoux, E; Rougerie, R; Lakatos, F; Roques, A; Lopez-Vaamonde, C
2009-08-01
Biological invasions usually start with a small number of founder individuals. These founders are likely to represent a small fraction of the total genetic diversity found in the source population. Our study set out to trace genetically the geographical origin of the horse-chestnut leafminer, Cameraria ohridella, an invasive microlepidopteran whose area of origin is still unkown. Since its discovery in Macedonia 25 years ago, this insect has experienced an explosive westward range expansion, progressively colonizing all of Central and Western Europe. We used cytochrome oxidase I sequences (DNA barcode fragment) and a set of six polymorphic microsatellites to assess the genetic variability of C. ohridella populations, and to test the hypothesis that C. ohridella derives from the southern Balkans (Albania, Macedonia and Greece). Analysis of mtDNA of 486 individuals from 88 localities allowed us to identify 25 geographically structured haplotypes. In addition, 480 individuals from 16 populations from Europe and the southern Balkans were genotyped for 6 polymorphic microsatellite loci. High haplotype diversity and low measures of nucleotide diversities including a significantly negative Tajima's D indicate that C. ohridella has experienced rapid population expansion during its dispersal across Europe. Both mtDNA and microsatellites show a reduction in genetic diversity of C. ohridella populations sampled from artificial habitats (e.g. planted trees in public parks, gardens, along roads in urban or sub-urban areas) across Europe compared with C. ohridella sampled in natural stands of horse-chestnuts in the southern Balkans. These findings suggest that European populations of C. ohridella may indeed derive from the southern Balkans.
-
Therapeutic approaches to slowing the progression of diabetic nephropathy - is less best?
Vivian, Eva; Mannebach, Chelsea
2013-03-27
Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors are known to reduce proteinuria and have been the first-line agents in the management of diabetic nephropathy for the past 20 years. This review covers recent studies that compare the benefit of additional blockage of the renin-angiotensin-aldosterone system through combination therapy with an ACE inhibitor and ARB, or a direct renin inhibitor (DRI), to monotherapy. Primary and review articles that addressed the pathophysiology, diagnosis, and therapeutic options for attenuating the progression of diabetic nephropathy were retrieved through a MEDLINE search (January 1990 to December 2012) and the bibliographies of identified articles were reviewed. English language sources were searched using the following search terms: diabetes mellitus, nephropathy, proteinuria, ACE inhibitors, ARBs, and DRIs. Randomized, placebo-controlled, short- and long-term studies published in peer-reviewed journals that were determined to be methodologically sound, with appropriate statistical analysis of the results, were selected for inclusion in this review. Adult (≥18 years) patients with diabetic nephropathy. Serum creatinine level was used to estimate glomerular filtration rate (GFR). GFR was calculated using the four-variable Modification of Diet in Renal Disease formula. The urine albumin-to-creatinine ratio was measured at baseline and at the conclusion of each study. A value between 3.4 mg/mmol and below 33.9 mg/mmol was defined as microalbuminuria. A value of 33.9 mg/mmol or more (approximately 300 mg/g creatinine) was defined as macroalbuminuria. ACE inhibitors and ARBs are now the mainstay of treatment for diabetic nephropathy. However, combination therapy with an ACE inhibitor and an ARB, or DRI, has not been found to be more effective than monotherapy with an ACE inhibitor or ARB, and may increase the risk of hyperkalemia or acute kidney injury. Both ACE inhibitors and ARBs remain
-
The National Guard State Partnership Program and Regional Security in the Western Balkans
2014-12-12
expand at the expense of its neighbors, or threaten regional peace and security. Today’s threats in the Western Balkans conceptually resemble the...general threats to the majority of governments in the EU, such as terrorism, arms and human trafficking, international criminal activities, and other...arms and human trafficking, international criminal activities, and other transnational threats . For stakeholders within the region as well as for
-
Groundhog Day: Expectation Management by Examining Warfare in the Early Twentieth Century Balkans
2007-06-15
Balkan Peninsula around the Former Republic of Yugoslavia and its neighboring nations. This excludes Romania 7 and southern Hungary, but movement...of modern-day Romania . With the expansion to include more of the Peninsula, however, things began to change. Missionaries from Constantinople had...inclusion of Orthodox Christianity. Second, obviously using the Byzantine Empire as the model, the sovereign was the originator of law. However, the powers
-
Thrombospondin Type-1 Domain-Containing 7A in Idiopathic Membranous Nephropathy
Meyer-Schwesinger, Catherine; Seitz-Polski, Barbara; Ma, Hong; Zahner, Gunther; Dolla, Guillaume; Hoxha, Elion; Helmchen, Udo; Dabert-Gay, Anne-Sophie; Debayle, Delphine; Merchant, Michael; Klein, Jon; Salant, David J.; Stahl, Rolf A.K.; Lambeau, Gérard
2014-01-01
BACKGROUND Idiopathic membranous nephropathy is an autoimmune disease. In approximately 70% of patients, it is associated with autoantibodies against the phospholipase A2 receptor 1 (PLA2R1). Antigenic targets in the remaining patients are unknown. METHODS Using Western blotting, we screened serum samples from patients with idiopathic membranous nephropathy, patients with other glomerular diseases, and healthy controls for antibodies against human native glomerular proteins. We partially purified a putative new antigen, identified this protein by means of mass spectrometry of digested peptides, and validated the results by analysis of recombinant protein expression, immunoprecipitation, and immunohistochemical analysis. RESULTS Serum samples from 6 of 44 patients in a European cohort and 9 of 110 patients in a Boston cohort with anti-PLA2R1–negative idiopathic membranous nephropathy recognized a glomerular protein that was 250 kD in size. None of the serum samples from the 74 patients with idiopathic membranous nephropathy who were sero-positive for anti-PLA2R1 antibodies, from the 76 patients with other glomerular diseases, and from the 44 healthy controls reacted against this antigen. Although this newly identified antigen is clearly different from PLA2R1, it shares some biochemical features, such as N-glycosylation, membranous location, and reactivity with serum only under nonreducing conditions. Mass spectrometry identified this antigen as thrombospondin type-1 domain-containing 7A (THSD7A). All reactive serum samples recognized recombinant THSD7A and immunoprecipitated THSD7A from glomerular lysates. Moreover, immunohistochemical analyses of biopsy samples from patients revealed localization of THSD7A to podocytes, and IgG eluted from one of these samples was specific for THSD7A. CONCLUSIONS In our cohort, 15 of 154 patients with idiopathic membranous nephropathy had circulating autoantibodies to THSD7A but not to PLA2R1, a finding that suggests a distinct
-
Mohamed, Riyaz; Jayakumar, Calpurnia; Chen, Feng; Fulton, David; Stepp, David; Gansevoort, Ron T; Ramesh, Ganesan
2016-03-01
Diabetes is the leading cause of kidney failure, accounting for >45% of new cases of dialysis. Diabetic nephropathy is characterized by inflammation, fibrosis, and oxidant stress, pathologic features that are shared by many other chronic inflammatory diseases. The cytokine IL-17A was initially implicated as a mediator of chronic inflammatory diseases, but recent studies dispute these findings and suggest that IL-17A can favorably modulate inflammation. Here, we examined the role of IL-17A in diabetic nephropathy. We observed that IL-17A levels in plasma and urine were reduced in patients with advanced diabetic nephropathy. Type 1 diabetic mice that are genetically deficient in IL-17A developed more severe nephropathy, whereas administration of low-dose IL-17A prevented diabetic nephropathy in models of type 1 and type 2 diabetes. Moreover, IL-17A administration effectively treated, prevented, and reversed established nephropathy in genetic models of diabetes. Protective effects were also observed after administration of IL-17F but not IL-17C or IL-17E. Notably, tubular epithelial cell-specific overexpression of IL-17A was sufficient to suppress diabetic nephropathy. Mechanistically, IL-17A administration suppressed phosphorylation of signal transducer and activator of transcription 3, a central mediator of fibrosis, upregulated anti-inflammatory microglia/macrophage WAP domain protein in an AMP-activated protein kinase-dependent manner and favorably modulated renal oxidative stress and AMP-activated protein kinase activation. Administration of recombinant microglia/macrophage WAP domain protein suppressed diabetes-induced albuminuria and enhanced M2 marker expression. These observations suggest that the beneficial effects of IL-17 are isoform-specific and identify low-dose IL-17A administration as a promising therapeutic approach in diabetic kidney disease. Copyright © 2016 by the American Society of Nephrology.
-
Wijkström, Julia; Jayasumana, Channa; Dassanayake, Rajeewa; Priyawardane, Nalin; Godakanda, Nimali; Siribaddana, Sisira; Ring, Anneli; Hultenby, Kjell; Söderberg, Magnus; Elinder, Carl-Gustaf; Wernerson, Annika
2018-01-01
In Sri Lanka, an endemic of chronic kidney disease of unknown origin (CKDu) is affecting rural communities. The endemic has similarities with Mesoamerican Nephropathy (MeN) in Central America, however it has not yet been clarified if the endemics are related diagnostic entities. We designed this study of kidney biopsies from patients with CKDu in Sri Lanka to compare with MeN morphology. Eleven patients with CKDu were recruited at the General Hospital, Polonnaruwa, using similar inclusion and exclusion criteria as our previous MeN studies. Inclusion criteria were 20-65 years of age and plasma creatinine 100-220 μmol/L. Exclusion criteria were diabetes mellitus, uncontrolled hypertension and albuminuria >1g/24h. Kidney biopsies, blood and urine samples were collected, and participants answered a questionnaire. Included participants were between 27-61 years of age and had a mean eGFR of 38±14 ml/min/1.73m2. Main findings in the biopsies were chronic glomerular and tubulointerstitial damage with glomerulosclerosis (8-75%), glomerular hypertrophy and mild to moderate tubulointerstitial changes. The morphology was more heterogeneous and interstitial inflammation and vascular changes were more common compared to our previous studies of MeN. In two patients the biopsies showed morphological signs of acute pyelonephritis but urine cultures were negative. Electrolyte disturbances with low levels of serum sodium, potassium, and/or magnesium were common. In the urine, only four patients displayed albuminuria, but many patients exhibited elevated α-1-microglobulin and magnesium levels. This is the first study reporting detailed biochemical and clinical data together with renal morphology, including electron microscopy, from Sri Lankan patients with CKDu. Our data show that there are many similarities in the biochemical and morphological profile of the CKDu endemics in Central America and Sri Lanka, supporting a common etiology. However, there are differences, such as a more
-
Jayasumana, Channa; Dassanayake, Rajeewa; Priyawardane, Nalin; Godakanda, Nimali; Siribaddana, Sisira; Ring, Anneli; Hultenby, Kjell; Söderberg, Magnus; Elinder, Carl-Gustaf; Wernerson, Annika
2018-01-01
In Sri Lanka, an endemic of chronic kidney disease of unknown origin (CKDu) is affecting rural communities. The endemic has similarities with Mesoamerican Nephropathy (MeN) in Central America, however it has not yet been clarified if the endemics are related diagnostic entities. We designed this study of kidney biopsies from patients with CKDu in Sri Lanka to compare with MeN morphology. Eleven patients with CKDu were recruited at the General Hospital, Polonnaruwa, using similar inclusion and exclusion criteria as our previous MeN studies. Inclusion criteria were 20–65 years of age and plasma creatinine 100–220 μmol/L. Exclusion criteria were diabetes mellitus, uncontrolled hypertension and albuminuria >1g/24h. Kidney biopsies, blood and urine samples were collected, and participants answered a questionnaire. Included participants were between 27–61 years of age and had a mean eGFR of 38±14 ml/min/1.73m2. Main findings in the biopsies were chronic glomerular and tubulointerstitial damage with glomerulosclerosis (8–75%), glomerular hypertrophy and mild to moderate tubulointerstitial changes. The morphology was more heterogeneous and interstitial inflammation and vascular changes were more common compared to our previous studies of MeN. In two patients the biopsies showed morphological signs of acute pyelonephritis but urine cultures were negative. Electrolyte disturbances with low levels of serum sodium, potassium, and/or magnesium were common. In the urine, only four patients displayed albuminuria, but many patients exhibited elevated α-1-microglobulin and magnesium levels. This is the first study reporting detailed biochemical and clinical data together with renal morphology, including electron microscopy, from Sri Lankan patients with CKDu. Our data show that there are many similarities in the biochemical and morphological profile of the CKDu endemics in Central America and Sri Lanka, supporting a common etiology. However, there are differences, such
-
Ginkgo biloba Extract for Patients with Early Diabetic Nephropathy: A Systematic Review
Zhang, Lei; Mao, Wei; Guo, Xinfeng; Wu, Yifan; Li, Chuang; Lu, Zhaoyu; Su, Guobin; Li, Xiaoyan; Liu, Zhuangzhu; Guo, Rong; Jie, Xina; Wen, Zehuai; Liu, Xusheng
2013-01-01
Objectives. To evaluate the effectiveness and safety of a Ginkgo biloba extract for patients with early diabetic nephropathy. Methods. Randomised controlled trials (RCTs) conducted on adults with early diabetic nephropathy which used Gingko biloba extract were included. The major databases were searched, and manufacturers of Gingko biloba products were contacted for information on any published or unpublished studies. Two authors independently extracted the data from the included studies. Data analysis was conducted using Review Manager 5.0 software. Results. Sixteen RCTs were included. Ginkgo biloba extract decreased the urinary albumin excretion rate (UAER), fasting blood glucose (FBG), serum creatinine (SCR), and blood urea nitrogen (BUN). The extract also improved hemorheology. The methodological quality in the included studies was low. The explicit generation of the allocation sequence was described in only 6 trials. None of the included trials were confirmed to use blinding. Three studies had observed adverse events. One study using angiotensin-converting enzyme inhibitor (ACEi) reported mild cough in both groups. No serious adverse effects were reported. Conclusions. Gingko biloba extract is a valuable drug which has prospect in treating early diabetic nephropathy, especially with high UAER baseline level. The safety for early diabetic nephropathy is uncertain. Long-term, double-blinded RCTs with large sample sizes are still needed to provide stronger evidence. PMID:23533513
-
Spontaneous Remission of Nephrotic Syndrome in Idiopathic Membranous Nephropathy
Polanco, Natalia; Gutiérrez, Elena; Covarsí, Adelardo; Ariza, Francisco; Carreño, Agustín; Vigil, Ana; Baltar, José; Fernández-Fresnedo, Gema; Martín, Carmen; Pons, Salvador; Lorenzo, Dolores; Bernis, Carmen; Arrizabalaga, Pilar; Fernández-Juárez, Gema; Barrio, Vicente; Sierra, Milagros; Castellanos, Ines; Espinosa, Mario; Rivera, Francisco; Oliet, Aniana; Fernández-Vega, Francisco
2010-01-01
Spontaneous remission is a well known characteristic of idiopathic membranous nephropathy, but contemporary studies describing predictors of remission and long-term outcomes are lacking. We conducted a retrospective, multicenter cohort study of 328 patients with nephrotic syndrome resulting from idiopathic membranous nephropathy that initially received conservative therapy. Spontaneous remission occurred in 104 (32%) patients: proteinuria progressively declined after diagnosis until remission of disease at 14.7 ± 11.4 months. Although spontaneous remission was more frequent with lower levels of baseline proteinuria, it also frequently occurred in patients with massive proteinuria: 26% among those with baseline proteinuria 8 to 12 g/24 h and 22% among those with proteinuria >12 g/24 h. Baseline serum creatinine and proteinuria, treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor antagonists, and a >50% decline of proteinuria from baseline during the first year of follow-up were significant independent predictors for spontaneous remission. Only six patients (5.7%) experienced a relapse of nephrotic syndrome. The incidence of death and ESRD were significantly lower among patients with spontaneous remission. In conclusion, spontaneous remission is common among patients with nephrotic syndrome resulting from membranous nephropathy and carries a favorable long-term outcome with a low incidence of relapse. A decrease in proteinuria >50% from baseline during the first year predicts spontaneous remission. PMID:20110379
-
ERIC Educational Resources Information Center
Klemencic, Manja; Zgaga, Pavel
2014-01-01
The article analyzes the public-private dynamics in the context of eight Western Balkan countries (Albania, Bosnia and Herzegovina, Croatia, Former Yugoslav Republic of Macedonia, Kosovo, Montenegro, Serbia, and Slovenia). This article examines whether and to what extent these governments "level the playing field" between private and…
-
Diabetic nephropathy in Africa: A systematic review
Noubiap, Jean Jacques N; Naidoo, Jashira; Kengne, Andre P
2015-01-01
AIM: To determine the prevalence and incidence of diabetic nephropathy in Africa. METHODS: We performed a systematic narrative review of published literature following the MOOSE Guidelines for Meta-Analysis and Systematic Reviews of Observational Studies. We searched PubMed-MEDLINE for all articles published in English and French languages between January 1994 and July 2014 using a predefined strategy based on the combination of relevant terms and the names of each of the 54 African countries and African sub-regions to capture the largest number of studies, and hand-searched the reference lists of retrieved articles. Included studies reported on the prevalence, incidence or determinants of chronic kidney disease (CKD) in people with diabetes within African countries. RESULTS: Overall, we included 32 studies from 16 countries; two being population-based studies and the remaining being clinic-based surveys. Most of the studies (90.6%) were conducted in urban settings. Methods for assessing and classifying CKD varied widely. Measurement of urine protein was the most common method of assessing kidney damage (62.5% of studies). The overall prevalence of CKD varied from 11% to 83.7%. Incident event rates were 94.9% for proteinuria at 10 years of follow-up, 34.7% for end-stage renal disease at 5 years of follow-up and 18.4% for mortality from nephropathy at 20 years of follow-up. Duration of diabetes, blood pressure, advancing age, obesity and glucose control were the common determinants of kidney disease. CONCLUSION: The burden of CKD is important among people with diabetes in Africa. High quality data from large population-based studies with validated measures of kidney function are still needed to better capture the magnitude and characteristics of diabetic nephropathy in Africa. PMID:26069725
-
[Endemic treponematoses in Maputo, Mozambique].
Clyti, E; dos Santos, R Bastos
2007-05-01
Endemic treponematoses are present in inter-tropical countries in Africa, America, Indonesia and Papua New Guinea. Epidemiology and transmission of the disease are well known. After eradication in some countries after mass treatment in 1950-60, a resurgence of endemic treponematoses has been reported since 1980-90. We present 2 cases of endemic syphilis from the dermatology unit of the Maputo hospital, the first to be described in Mozambique. The endemic syphilis was probably facilitated by the social conditions induced by the Mozambican civil war between 1975 and 1993.
-
Dall'Acqua, F; Paladini, C; Meiswinkel, R; Savini, L; Calistri, P
2006-01-01
During the recent severe outbreaks of bluetongue (BT) in the Mediterranean Basin, the BT virus (BTV) spread beyond its historical limits into the Balkan region. One of the primary impacts of BT is the cessation in livestock trade which can have severe economic and social consequences. The authors briefly describe the development of the collaborative East-BTnet programme which aims to assist all affected and at-risk Balkan states and adjoining countries in the management of BT, and in the development of individual national surveillance systems. The beneficiary countries involved, and led by the World organisation for animal health (Office International des Epizooties) Collaborating Centre for veterinary training, epidemiology, food safety and animal welfare of the Istituto Zooprofilattico dell'Abruzzo e del Molise 'G. Caporale' in collaboration with the Institute for the Protection and the Security of the Citizen, the European Commission Joint Research Centre (IPSC-JRC), were Albania, Bosnia-Herzegovina, Bulgaria, Croatia, Cyprus, the Former Yugoslavia Republic of Macedonia, Kosovo, Malta, Romania, Serbia and Montenegro, Slovenia and Turkey. A regional web-based surveillance network is a valuable tool for controlling and managing transboundary animal diseases such as BT. Its implementation in the Balkan region and in adjoining areas of south-eastern Europe is described and discussed.
-
Waasdorp, Maaike; Duitman, JanWillem; Florquin, Sandrine; Spek, C Arnold
2018-04-24
Twenty years after the onset of diabetes, up to 40% of patients develop diabetic nephropathy. Protease-activated receptor-1 (PAR-1) has recently been shown to aggravate the development of experimental diabetic nephropathy. PAR-1 deficient mice develop less albuminuria and glomerular lesions and PAR-1 stimulation induces proliferation and fibronectin production in mesangial cells in vitro . Vorapaxar is a clinically available PAR-1 inhibitor which is currently used for secondary prevention of ischemic events. The aim of this study was to investigate in a preclinical setting whether vorapaxar treatment may be a novel strategy to reduce diabetes-induced kidney damage. While control treated diabetic mice developed significant albuminuria, mesangial expansion and glomerular fibronectin deposition, diabetic mice on vorapaxar treatment did not show any signs of kidney damage despite having similar levels of hyperglycemia. These data show that PAR-1 inhibition by vorapaxar prevents the development of diabetic nephropathy in this preclinical animal model for type I diabetes and pinpoint PAR-1 as a novel therapeutic target to pursue in the setting of diabetic nephropathy. 22 C57Bl/6 mice were made diabetic using multiple low-dose streptozotocin injections (50 mg/kg) and 22 littermates served as non-diabetic controls. Four weeks after the induction of diabetes, 11 mice of each group were assigned to control or vorapaxar treatment. Mice were sacrificed after 20 weeks of treatment and kidney damage was evaluated.
-
Effect of strawberry (Fragaria × ananassa) leaf extract on diabetic nephropathy in rats
Ibrahim, Doaa S; Abd El-Maksoud, Marwa A E
2015-01-01
Diabetic nephropathy is a clinical syndrome characterized by albuminuria, hypertension and progressive renal insufficiency. The aim of this study was to investigate the effect of strawberry (Fragaria × ananassa) leaf extract on diabetic nephropathy in rats. Streptozotocin (STZ) diabetic rats were orally treated with three doses (50, 100 and 200 mg/kg) of strawberry leaf extract for 30 days. Nephropathy biomarkers in plasma and kidney were examined at the end of the experiment. The three doses of strawberry leaf extract significantly decreased the levels of blood glucose, urea nitrogen, plasma creatinine, kidney injury molecule (Kim)-1, renal malondialdehyde (MDA), tumour necrosis factor alpha (TNF-α), interleukin (IL)- 6 and caspase-3 in diabetic rats. Meanwhile, the levels of plasma insulin, albumin, uric acid, renal catalase (CAT), superoxide dismutase (SOD) and vascular endothelial growth factor A (VEGF-A) were significantly elevated in diabetic rats treated with strawberry leaf extract. These results indicate the role of strawberry leaves extract as anti-diabetic, antioxidant, anti-inflammatory and anti-apoptosis in diabetic nephropathy. PMID:25645466
-
Yang, Xiao-Hui; Feng, Shi-Ya; Yu, Yang; Liang, Zhou
2018-01-01
This study aims to explore the relationship between the methylation of matrix metalloproteinase (MMP)-9 gene promoter region and diabetic nephropathy (DN) through the detection of the methylation level of MMP-9 gene promoter region in the peripheral blood of patients with DN in different periods and serum MMP-9 concentration. The methylation level of the MMP-9 gene promoter region was detected by methylation-specific polymerase chain reaction (MSP), and the content of MMP-9 in serum was determined by enzyme-linked immunosorbent assay (ELISA). Results of the statistical analysis revealed that serum MMP-9 protein expression levels gradually increased in patients in the simple diabetic group, early diabetic nephropathy group and clinical diabetic nephropathy group, compared with the control group; and the difference was statistically significant (P < 0.05). Compared with the control group, the methylation levels of MMP-9 gene promoter regions gradually decreased in patients in the simple diabetic group, early diabetic nephropathy group, and clinical diabetic nephropathy group; and the difference was statistically significant (P < 0.05). Furthermore, correlation analysis results indicated that the demethylation levels of the MMP-9 gene promoter region was positively correlated with serum protein levels, urinary albumin to creatinine ratio (UACR), urea and creatinine; and was negatively correlated with GFR. The demethylation of the MMP-9 gene promoter region may be involved in the occurrence and development of diabetic nephropathy by regulating the expression of MMP-9 protein in serum.
-
Veličković, N; Ferreira, E; Djan, M; Ernst, M; Obreht Vidaković, D; Monaco, A; Fonseca, C
2016-01-01
Wild boar (Sus scrofa), one of the most widespread wildlife species, has entered a stage of continuous growth in Europe, and could even be considered a pest species. We analysed microsatellite variability in 723 wild boars from across Europe, including the northern Dinaric Balkans. Our aims were: (1) to define the population structure of wild boars in the Balkans and its relation with other European populations; (2) to estimate effective populations sizes, levels of intra- and inter-population diversity, inbreeding migration and gene flow patterns; (3) to test subpopulations for bottlenecks; (4) to interpret these results in light of current knowledge about the demographic history of wild boars in Europe; and (5) to discuss the relevance of these findings for management and conservation. Strong population structuring was observed and 14 subpopulations were revealed. High genetic diversity was found, and besides the well-known identity of the Italian populations of Sardinia and Castelporziano, we bring new insights into other potential relevant, refugial populations such as Littoral Slovenia, South Portugal, North-western Iberia and an entire cluster in the Balkans. There was evidence of gene flow going from these refugial subpopulations towards less peripheral and more admixed subpopulations. Recent population bottlenecks and expansions were detected, mostly in the peninsular refuge subpopulations. The results are consistent with the fluctuations of wild boar numbers in Europe since the beginning of the twentieth century. These results should be taken into account in future conservation and management plans for wild boar populations in Europe. PMID:27436523
-
Extending knowledge of the public awareness of aphasia in the Balkans: Serbia and Montenegro.
Vuković, Mile; Matić, Dušanka; Kovač, Ana; Vuković, Irena; Code, Chris
2017-11-01
Public awareness of aphasia has been surveyed in a number of countries revealing that it is universally low. We report results of surveys in the Balkan countries Serbia and Montenegro and compare results with data from Croatia and Slovenia. Convenience surveys of the general public were conducted in public places like shopping centers/malls and parks in Serbia (N = 400) and Montenegro (N = 500) using an adapted version of the public awareness of aphasia survey questionnaire. Respondents were asked whether they have heard of aphasia and tested with questions about aphasia. Information on gender, age, occupation and education was recorded. Twelve percent (Serbia) and 11% (Montenegro) had heard of aphasia, but just 4% (Serbia) and 3.2% (Montenegro) had a basic knowledge of aphasia. Age, gender and occupation interacted variably with awareness. Between 16% (Slovenia) and 60% (Croatia) said they had heard of aphasia (10.5% overall mean for the four countries) and basic knowledge of aphasia across the four countries ranged between 3.2 and 7%. Levels of awareness of aphasia in the Balkans are low and variably associated with age, gender, socio-economic and educational levels. Respondents with some knowledge of aphasia gained it through personal or professional interaction with aphasia or the media. The data provide a basis for awareness raising in Balkan countries to reduce stigmatization, improve community access and understanding. Implications for rehabilitation Awareness of aphasia is low universally, even among healthcare workers. Low public awareness of a condition, like aphasia, results in under-funded research and service provision. In order to raise public awareness of aphasia we need to know how many members of the general public know about it. Improvements in public awareness could positively affect funding, the quality of services, and the public understanding and acceptance of individuals with aphasia in the community. Improving awareness of aphasia in
-
Latifi, Rifat; Merrell, Ronald C; Doarn, Charles R; Hadeed, George J; Bekteshi, Flamur; Lecaj, Ismet; Boucha, Kathe; Hajdari, Fatmir; Hoxha, Astrit; Koshi, Dashurije; de Leonni Stanonik, Mateja; Berisha, Blerim; Novoberdaliu, Kadri; Imeri, Arben; Weinstein, Ronald S
2009-12-01
Establishing sustainable telemedicine has become a goal of many developing countries around the world. Yet, despite initiatives from a select few individuals and on occasion from various governments, often these initiatives never mature to become sustainable programs. The introduction of telemedicine and e-learning in Kosova has been a pivotal step in advancing the quality and availability of medical services in a region whose infrastructure and resources have been decimated by wars, neglect, lack of funding, and poor management. The concept and establishment of the International Virtual e-Hospital (IVeH) has significantly impacted telemedicine and e-health services in the Balkans. The success of the IVeH in Kosova has led to the development of similar programs in other Balkan countries and other developing countries in the hope of modernizing and improving their healthcare infrastructure. A comprehensive, four-pronged strategy, "Initiate-Build-Operate-Transfer" (IBOT), may be a useful approach in establishing telemedicine and e-health educational services in developing countries. The development strategy, IBOT, used by the IVeH to establish and develop telemedicine programs, was discussed. IBOT includes assessment of healthcare needs of each country, the development of a curriculum and education program, the establishment of a nationwide telemedicine network, and the integration of the telemedicine program into the healthcare infrastructure. The endpoint is the transfer of a sustainable telehealth program to the nation involved. By applying IBOT, a sustainable telemedicine program of Kosova has been established as an effective prototype for telemedicine in the Balkans. Once fully matured, the program will be transitioned to the national Ministry of Health, which ensures the sustainability and ownership of the program. Similar programs are being established in Albania, Macedonia, and other countries around the world. The IBOT model has been effective in creating
-
Bagshaw, Sean M; Ghali, William A
2004-01-01
Background Contrast-induced nephropathy is an important cause of acute renal failure. We assess the efficacy of acetylcysteine for prevention of contrast-induced nephropathy among patients undergoing intravascular angiography. Methods We conducted a systematic review and meta-analysis of randomized controlled trials comparing prophylactic acetylcysteine plus hydration versus hydration alone in patients undergoing intravascular angiography. Studies were identified by searching MEDLINE, EMBASE, and CENTRAL databases. Our main outcome measures were the risk of contrast-induced nephropathy and the difference in serum creatinine between acetylcysteine and control groups at 48 h. Results Fourteen studies involving 1261 patients were identified and included for analysis, and findings were heterogeneous across studies. Acetylcysteine was associated with a significantly reduced incidence of contrast-induced nephropathy in five studies, and no difference in the other nine (with a trend toward a higher incidence in six of the latter studies). The pooled odds ratio for contrast-induced nephropathy with acetylcysteine relative to control was 0.54 (95% CI, 0.32–0.91, p = 0.02) and the pooled estimate of difference in 48-h serum creatinine for acetylcysteine relative to control was -7.2 μmol/L (95% CI -19.7 to 5.3, p = 0.26). These pooled values need to be interpreted cautiously because of the heterogeneity across studies, and due to evidence of publication bias. Meta-regression suggested that the heterogeneity might be partially explained by whether the angiography was performed electively or as emergency. Conclusion These findings indicate that published studies of acetylcysteine for prevention of contrast-induced nephropathy yield inconsistent results. The efficacy of acetylcysteine will remain uncertain unless a large well-designed multi-center trial is performed. PMID:15500690
-
Bandak, Ghassan; Jones, Bruce A; Li, Jian; Yee, Jerry; Umanath, Kausik
2014-02-01
Antibody-mediated anti-glomerular basement membrane (anti-GBM) disease occurs rarely in the presence of another B-cell disorder, membranous nephropathy. The coexistence of these two autoimmune disorders would be anticipated to require differing, specific therapies targeted to each disease process. We describe a case of concomitant membranous nephropathy and anti-GBM disease in which conventional therapy, including steroids, plasmapheresis and cyclophosphamide, failed to attenuate the anti-GBM disease, yet responded to an alternative treatment of rituximab. This B-cell directed, monoclonal, chimeric antibody treatment substantially reduced anti-GBM antibody titers and led to discontinuation of plasmapheresis, while maintaining the remission of membranous nephropathy and anti-GBM disease.
-
Yun, Byeong Hwa; Rosenquist, Thomas; Sidorenko, Viktoriya; Iden, Charles; Chung-Hsin, Chen; Pu, Yeong-Shiau; Bonala, Radha; Johnson, Francis; Dickman, Kathleen G.; Grollman, Arthur P.; Turesky, Robert J.
2012-01-01
Aristolochic acids (AAs) are a structurally-related family of nephrotoxic and carcinogenic nitrophenanthrene compounds found in Aristolochia herbaceous plants, many of which have been used worldwide for medicinal purposes. AAs have been implicated in the etiology of so-called Chinese herbs nephropathy and of Balkan endemic nephropathy. Both of these disease syndromes are associated with carcinomas of the upper urinary tract (UUC). 8-Methoxy-6-nitrophenanthro-[3,4-d]-1,3-dioxolo-5-carboxylic acid (AA-I) is a principal component of Aristolochia herbs. Following metabolic activation, AA-I reacts with DNA to form aristolactam (AL-I)-DNA adducts. We have developed a sensitive analytical method, using ultra-performance liquid chromatography-electrospray ionization/multistage mass spectrometry (UPLC-ESI/MSn) with a linear quadrupole ion-trap mass spectrometer, to measure 7-(deoxyadenosin-N6-yl) aristolactam I (dA-AL-I) and 7-(deoxyguanosin-N2-yl) aristolactam I (dG-AL-I) adducts. Using 10 μg of DNA for measurements, the lower limits of quantitation of dA-AL-I and dG-AL-I are, respectively, 0.3 and 1.0 adducts per 108 DNA bases. We have used UPLC-ESI/MSn to quantify AL-DNA adducts in tissues of rodents exposed to AA, and in the renal cortex of patients with UUC who reside in Taiwan, where the incidence of this uncommon cancer is the highest reported for any country in the world. In human tissues, dA-AL-I was detected at levels ranging from 9 to 338 adducts per 108 DNA bases, whereas dG-AL-I was not found. We conclude that UPLC-ESI/MSn is a highly sensitive, specific and robust analytical method, positioned to supplant 32P-postlabeling techniques currently used for biomonitoring of DNA adducts in human tissues. Importantly, UPLC-ESI/MSn could be used to document exposure to AA, the toxicant responsible for AA nephropathy and its associated UUC. PMID:22515372
-
Takao, Toshiko; Matsuyama, Yutaka; Suka, Machi; Yanagisawa, Hiroyuki; Kikuchi, Masatoshi; Kawazu, Shoji
2014-01-01
To analyze time-to-effect relationships between systolic blood pressure (SBP) and the risks of development of nephropathy and retinopathy in patients with type 2 diabetes. We retrospectively enrolled 647 patients with type 2 diabetes who first visited our hospital between 1995 and 1996, made ≥1 hospital visit per year, had been followed-up for ≥1year, and had undergone ≥4 SBP measurements. Of these, 352 with normoalbuminuria and 516 without retinopathy were followed through June 2012. Nephropathy developed in 90 patients and retinopathy in 113. Hazard ratios (HRs) for time-dependent SBP-associated nephropathy and retinopathy were the highest during 1year preceding each endpoint or censoring. The HRs for nephropathy had been steadily lower during the preceding 1-17 years, while that for retinopathy had been lower during the preceding 1-5 years and constant during the preceding 5-17 years. The time-to-effect relationship with SBP differed for the development of nephropathy and retinopathy. The long-term effect was obvious for nephropathy and borderline for retinopathy, while the short-term effect was stronger and evident for both. Continuous SBP lowering is necessary to prevent nephropathy, whereas SBP control during the preceding 5years seems to be important to prevent retinopathy. Copyright © 2014 Elsevier Inc. All rights reserved.
-
Yamamoto, Yoshihiko; Maeshima, Yohei; Kitayama, Hiroyuki; Kitamura, Shinji; Takazawa, Yuki; Sugiyama, Hitoshi; Yamasaki, Yasushi; Makino, Hirofumi
2004-07-01
In the early stage of diabetic nephropathy (one of the major microvascular complications of diabetes) glomerular hyperfiltration and hypertrophy are observed. It is clinically important to regulate glomerular hypertrophy for preventing glomerulosclerosis. The number of glomerular endothelial cells is known to be increased in diabetic nephropathy associated with enlarged glomerular tufts, suggesting that the mechanism is similar to that of angiogenesis. Tumstatin peptide is an angiogenesis inhibitor derived from type IV collagen and inhibits in vivo neovascularization induced by vascular endothelial growth factor (VEGF), one of the mediators of glomerular hypertrophy in diabetic nephropathy. Here, we show the effect of tumstatin peptide in inhibiting alterations in early diabetic nephropathy. Glomerular hypertrophy, hyperfiltration, and albuminuria were suppressed by tumstatin peptide (1 mg/kg) in streptozotocin-induced diabetic mice. Glomerular matrix expansion, the increase of total glomerular cell number and glomerular endothelial cells (CD31 positive), and monocyte/macrophage accumulation was inhibited by tumstatin peptide. Increase in renal expression of VEGF, flk-1, and angiopoietin-2, an antagonist of angiopoietin-1, was inhibited by tumstatin treatment in diabetic mice. Alteration of glomerular nephrin expression, a podocyte protein crucial for maintaining glomerular filtration barrier, was recovered by tumstatin in diabetic mice. Taken together, these results demonstrate the potential use of antiangiogenic tumstatin peptide as a novel therapeutic agent in early diabetic nephropathy.
-
Zhu, A N; Yang, X X; Sun, M Y; Zhang, Z X; Li, M
2015-03-13
We explored the associations of INSR and mTOR, 2 key genes in the insulin signaling pathway, and the susceptibility to type 2 diabetes mellitus and diabetic nephropathy. Three single-nucleotide polymorphisms (SNPs) (rs1799817, rs1051690, and rs2059806) in INSR and 3 SNPs (rs7211818, rs7212142, and rs9674559) in mTOR were genotyped using the Sequenom MassARRAY iPLEX platform in 89 type 2 diabetes patients without diabetic nephropathy, 134 type 2 diabetes patients with diabetic nephropathy, and 120 healthy control subjects. Statistical analysis based on unconditional logistic regression was carried out to determine the odds ratio (OR) and 95% confidence interval (95%CI) for each SNP. Combination analyses between rs2059806 and rs7212142 were also performed using the X(2) test and logistic regression. Among these 6 SNPs, 4 (rs1799817, rs1051690, rs7211818, and rs9674559) showed no association with type 2 diabetes mellitus or diabetic nephropathy. However, rs2059806 in INSR was associated with both type 2 diabetes mellitus (P = 0.033) and type 2 diabetic nephropathy (P = 0.018). The rs7212142 polymorphism in mTOR was associated with type 2 diabetic nephropathy (P = 0.010, OR = 0.501, 95%CI = 0.288- 0.871), but showed no relationship with type 2 diabetes mellitus. Combination analysis revealed that rs2059806 and rs7212142 had a combined effect on susceptibility to type 2 diabetes mellitus and diabetic nephropathy. Our results suggest that both INSR and mTOR play a role in the predisposition of the Han Chinese population to type 2 diabetic nephropathy, but the genetic predisposition may show some differences.
-
Beisswenger, P J; Moore, L L; Brinck-Johnsen, T; Curphey, T J
1993-01-01
RATIONALE: Advanced glycosylation end products (AGEs) may play an important role in the development of diabetic vascular sequelae. An AGE cross-link, pentosidine, is a sensitive and specific marker for tissue levels of AGEs. OBJECTIVES: To evaluate the role of AGEs in the development of diabetic nephropathy and retinopathy, we studied pentosidine levels and the clinical characteristics of 48 subjects with insulin-dependent diabetes mellitus. Diabetic nephropathy was classified as normal, microalbuminuria, or gross proteinuria, and retinopathy was graded as none, background, or proliferative. NEWLY OBSERVED FINDINGS: Significant elevation of pentosidine (P = 0.025) was found in subjects with microalbuminuria or gross proteinuria (73.03 +/- 9.47 vs 76.46 +/- 6.37 pmol/mg col) when compared with normal (56.96 +/- 3.26 pmol/mg col). Multivariate analysis to correct for age, duration of diabetes, and gender did not modify the results. Elevated pentosidine levels were also found in those with proliferative when compared with those with background retinopathy (75.86 +/- 5.66 vs 60.42 +/- 5.98 pmol/mg col) (P < 0.05). CONCLUSIONS: Microalbuminuria is associated with elevated levels of pentosidine similar to those found in overt diabetic nephropathy suggesting that elevated AGE levels are already present during the earliest detectable phase of diabetic nephropathy. Images PMID:8325987
-
Çavusoglu, T; Erbas, O; Karadeniz, T; Akdemir, O; Acikgoz, E; Karadeniz, M; Tuglu, M I; Ates, U
2014-06-01
One of the major concerns is a nephropathy in diabetes, which applies many different kinds of medicines. However, required level of the treatment of renal disease has not been achieved. To investigate and compare the effect of the enalapril and the exenatide on diabetic nephropathy in rats developed diabetes by streptozosin. 32 male Sprague Dawley rats were divided into 4 groups: (1) Control, (2) Diabetic (DM), (3) DM+ Enalapril, and (4) DM+ exenatide groups. Then, the animals were euthanized and their blood samples were collected by cardiac puncture for blood glucose; blood urea nitrogen (BUN), creatinin, and nephrectomy were performed for histopathologic examination, and urine samples were taken on stick for proteinuria. Administration of the enalapril or the exenatide in diabetic rats resulted in a significant reduction both fibronectin, induced nitric oxide synthase (i-NOS) expression in glomerular area and urine protein levels. It was shown that both of enalapril and exenatide protected the renal glomerulus more than diabetic group in the nephropathy histopathologically. The beneficial effects of enalapril and exenatide which reduces fibronectin, i-NOS expression and urine protein levels or increases recovery of glomerules, might be used for preventing the harmful effects of diabetic nephropathy. © Georg Thieme Verlag KG Stuttgart · New York.
-
Huang, Wen-Hung; Lin, Ja-Liang; Lin-Tan, Dan-Tzu; Hsu, Ching-Wei; Chen, Kuan-Hsing; Yen, Tzung-Hai
2013-01-01
Whether environmental lead exposure has a long-term effect on progressive diabetic nephropathy in type II diabetic patients remains unclear. A total of 107 type II diabetic patients with stage 3 diabetic nephropathy (estimated glomerular filtration rate (eGFR) range, 30-60 mL/min/1.73 m(2)) with normal body lead burden (BLB) (<600 μ g/72 hr in EDTA mobilization tests) and no history of exposure to lead were prospectively followed for 2 years. Patients were divided into high-normal BLB (>80 μ g) and low-normal BLB (<80 μ g) groups. The primary outcome was a 2-fold increase in the initial creatinine levels, long-term dialysis, or death. The secondary outcome was a change in eGFR over time. Forty-five patients reached the primary outcome within 2 years. Although there were no differences in baseline data and renal function, progressive nephropathy was slower in the low-normal BLB group than that in the high-normal BLB group. During the study period, we demonstrated that each 100 μ g increment in BLB and each 10 μ g increment in blood lead levels could decrease GFR by 2.2 mL/min/1.72 m(2) and 3.0 mL/min/1.72 m(2) (P = 0.005), respectively, as estimated by generalized equations. Moreover, BLB was associated with increased risk of achieving primary outcome. Environmental exposure to lead may have a long-term effect on progressive diabetic nephropathy in type II diabetic patients.
-
Varzari, Alexander; Kharkov, Vladimir; Nikitin, Alexey G; Raicu, Florina; Simonova, Kseniya; Stephan, Wolfgang; Weiss, Elisabeth H; Stepanov, Vadim
2013-01-01
Moldova has a rich historical and cultural heritage, which may be reflected in the current genetic makeup of its population. To date, no comprehensive studies exist about the population genetic structure of modern Moldavians. To bridge this gap with respect to paternal lineages, we analyzed 37 binary and 17 multiallelic (STRs) polymorphisms on the non-recombining portion of the Y chromosome in 125 Moldavian males. In addition, 53 Ukrainians from eastern Moldova and 54 Romanians from the neighboring eastern Romania were typed using the same set of markers. In Moldavians, 19 Y chromosome haplogroups were identified, the most common being I-M423 (20.8%), R-M17* (17.6%), R-M458 (12.8%), E-v13 (8.8%), R-M269* and R-M412* (both 7.2%). In Romanians, 14 haplogroups were found including I-M423 (40.7%), R-M17* (16.7%), R-M405 (7.4%), E-v13 and R-M412* (both 5.6%). In Ukrainians, 13 haplogroups were identified including R-M17 (34.0%), I-M423 (20.8%), R-M269* (9.4%), N-M178, R-M458 and R-M73 (each 5.7%). Our results show that a significant majority of the Moldavian paternal gene pool belongs to eastern/central European and Balkan/eastern Mediterranean Y lineages. Phylogenetic and AMOVA analyses based on Y-STR loci also revealed that Moldavians are close to both eastern/central European and Balkan-Carpathian populations. The data correlate well with historical accounts and geographical location of the region and thus allow to hypothesize that extant Moldavian paternal genetic lineages arose from extensive recent admixture between genetically autochthonous populations of the Balkan-Carpathian zone and neighboring Slavic groups.
-
Endemicity and evolutionary value: a study of Chilean endemic vascular plant genera
Scherson, Rosa A; Albornoz, Abraham A; Moreira-Muñoz, Andrés S; Urbina-Casanova, Rafael
2014-01-01
This study uses phylogeny-based measures of evolutionary potential (phylogenetic diversity and community structure) to evaluate the evolutionary value of vascular plant genera endemic to Chile. Endemicity is regarded as a very important consideration for conservation purposes. Taxa that are endemic to a single country are valuable conservation targets, as their protection depends upon a single government policy. This is especially relevant in developing countries in which conservation is not always a high resource allocation priority. Phylogeny-based measures of evolutionary potential such as phylogenetic diversity (PD) have been regarded as meaningful measures of the “value” of taxa and ecosystems, as they are able to account for the attributes that could allow taxa to recover from environmental changes. Chile is an area of remarkable endemism, harboring a flora that shows the highest number of endemic genera in South America. We studied PD and community structure of this flora using a previously available supertree at the genus level, to which we added DNA sequences of 53 genera endemic to Chile. Using discrepancy values and a null model approach, we decoupled PD from taxon richness, in order to compare their geographic distribution over a one-degree grid. An interesting pattern was observed in which areas to the southwest appear to harbor more PD than expected by their generic richness than those areas to the north of the country. In addition, some southern areas showed more PD than expected by chance, as calculated with the null model approach. Geological history as documented by the study of ancient floras as well as glacial refuges in the coastal range of southern Chile during the quaternary seem to be consistent with the observed pattern, highlighting the importance of this area for conservation purposes. PMID:24683462
-
Apelin impairs myogenic response to induce diabetic nephropathy in mice.
Zhang, Jia; Yin, Jiming; Wang, Yangjia; Li, Bin; Zeng, Xiangjun
2018-03-09
The cause of the invalid reaction of smooth muscle cells to mechanical stimulation that results in a dysfunctional myogenic response that mediates the disruption of renal blood flow (RBF) in patients with diabetes is debatable. The present study revealed that increased apelin concentration in serum of diabetic mice neutralized the myogenic response mediated by apelin receptor (APJ) and resulted in increased RBF, which promoted the progression of diabetic nephropathy. The results showed that apelin concentration, RBF, and albuminuria:creatinine ratio were all increased in kkAy mice, and increased RBF correlated positively with serum apelin both in C57 and diabetic mice. The increased RBF was accompanied by decreased phosphorylation of myosin light chain (MLC), β-arrestin, and increased endothelial NOS in glomeruli. Meanwhile, calcium, phosphorylation of MLC, and β-arrestin were decreased by high glucose and apelin treatment in cultured smooth muscle cells, as well. eNOS was increased by high glucose and increased by apelin in cultured endothelial cells (ECs). Knockdown of β-arrestin expression in smooth muscle cells cancelled phosphorylation of MLC induced by apelin. Therefore, apelin may induce the progression of diabetic nephropathy by counteracting the myogenic response in smooth muscle cells.-Zhang, J., Yin, J., Wang, Y., Li, B., Zeng, X. Apelin impairs myogenic response to induce diabetic nephropathy in mice.
-
NALP3-mediated inflammation is a principal cause of progressive renal failure in oxalate nephropathy
Knauf, Felix; Asplin, John R.; Granja, Ignacio; Schmidt, Insa M.; Moeckel, Gilbert; David, Rachel; Flavell, Richard A.; Aronson, Peter S.
2013-01-01
Oxalate nephropathy with renal failure is caused by multiple disorders causing hyperoxaluria due to either overproduction of oxalate (primary hyperoxaluria) or excessive absorption of dietary oxalate (enteric hyperoxaluria). To study the etiology of renal failure in crystal-induced kidney disease, we created a model of progressive oxalate nephropathy by feeding mice a diet high in soluble oxalate (high oxalate in the absence of dietary calcium). Renal histology was characterized by intratubular calcium-oxalate crystal deposition with an inflammatory response in the surrounding interstitium. Oxalate nephropathy was not found in mice fed a high oxalate diet that also contained calcium. NALP3, also known as cryopyrin, has been implicated in crystal-associated diseases such as gout and silicosis. Mice fed the diet high in soluble oxalate demonstrated increased NALP3 expression in the kidney. Nalp3-null mice were completely protected from the progressive renal failure and death that occurred in wild-type mice fed the diet high in soluble oxalate. NALP3-deficiency did not affect oxalate homeostasis, thereby excluding differences in intestinal oxalate handling to explain the observed phenotype. Thus, progressive renal failure in oxalate nephropathy results primarily from NALP3-mediated inflammation. PMID:23739234
-
Zhang, Lei; Zhang, La; Li, Yin; Guo, Xin-Feng; Liu, Xu-Sheng
2016-11-01
Compared with herbal drugs, medicine processed from animals (animal medicine) was thought to have more bioactive substances and higher activities. Biotransformation effect often plays an important role in their effect. However, researches about effect of animal medicine on diabetic nephropathy and applying animal medicine as natural bio-transformer were seldom reported. The purpose of this paper was to reveal the use of Bombyx Mori L. on diabetic nephropathy from ancient to modern times. The classical literature indicated that Saosi Decoction (), which contains Bombyx Mori L. or silkworm cocoon, was applied to treat disorders congruent with modern disease diabetic nephropathy from the Ming to Qing Dynasty in ancient China. Modern studies showed that Bombyx Mori L. contains four main active constituents. Among these, 1-deoxynojirimycin (1-DNJ) and quercetin showed promising potential to be new agents in diabetic nephropathy treatment. The concentrations of 1-DNJ and the activities of quercetin in Bombyx Mori L. are higher than in mulberry leaves, because of the biotransformation in the Bombyx Mori L. body. However, these specifific components need further human and mechanistic studies to determine their therapeutic potential for this challenging condition.
-
ERIC Educational Resources Information Center
Milovanovic, Suncica Macura; Kokic, Ivana Batarelo; Kristiansen, Selma Džemidžic; Gera, Ibolya; Ikonomi, Estevan; Kafedžic, Lejla; Milic, Tamara; Rexhaj, Xhavit; Spasovski, Ognen; Closs, Alison
2014-01-01
The article summarises the socio-political, cultural, economic and educational background to the Western Balkans region and outlines the wider qualitative research study that provided the data on early and pre-school educational opportunities in the seven countries involved; Albania, Bosnia and Herzegovina, Croatia, Kosovo (under United Nations…
-
Stamenković, G; Nikolić, V; Blagojević, J; Bugarski-Stanojević, V; Adnađević, T; Stanojević, M; Vujošević, M
2015-03-01
Dobrava-Belgrade virus (DOBV) is a hantavirus species that causes the most severe form of haemorrhagic fever with renal syndrome (HFRS) in Europe. DOBV has been detected in three Apodemus rodents: A. flavicollis, A. agrarius and A. ponticus. These emerging viruses appear throughout the Balkan Peninsula including Serbia as its central part. In this study, we examined the seroprevalence, molecular epidemiology and phylogenetics of DOBV from A. flavicollis captured at six Serbian localities. Furthermore, we applied microsatellite typing of host animal genome to analyse the role of host kinship in DOBV animal transmission. The overall IgG seropositivity rate over 3 years (2008-2010) was 11.9% (22/185). All seropositive samples were subjected to RT-PCR and DNA sequencing for S and L genome segments (pos. 291-1079 nt and 2999-3316 nt, respectively). DOBV was genetically detected in three samples from mountain Tara in western Serbia, a newly detected DOBV focus in the Balkans. No sequence data from human cases from Serbia are available for the studied period. However, collected DOBV isolates in this work phylogenetically clustered together with isolates from Serbian human cases dating from 2002, with 1.9% nucleotide divergence. We determined the level of kinship between seropositive and seronegative animal groups and found no significant difference, suggesting that horizontal virus transmission in the studied population was the same within and among the hatches. Our findings are the first genetic detection of DOBV in rodents in Serbia. We confirm wide and continuous hantavirus presence in the examined parts of the Balkans, underlying the necessity of continual monitoring of hantavirus circulation in A. flavicollis. © 2014 Blackwell Verlag GmbH.
-
Endemic Images and the Desensitization Process.
ERIC Educational Resources Information Center
Saigh, Philip A.; Antoun, Fouad T.
1984-01-01
Examined the effects of endemic images on levels of anxiety and achievement of 48 high school students. Results suggested that a combination of endemic images and study skills training was as effective as desensitization plus study skills training. Includes the endemic image questionnaire. (JAC)
-
Longman, Jack; Veres, Daniel; Finsinger, Walter; Ersek, Vasile
2018-05-29
The Balkans are considered the birthplace of mineral resource exploitation and metalworking in Europe. However, since knowledge of the timing and extent of metallurgy in southeastern Europe is largely constrained by discontinuous archaeological findings, the long-term environmental impact of past mineral resource exploitation is not fully understood. Here, we present a high-resolution and continuous geochemical record from a peat bog in western Serbia, providing a clear indication of the extent and magnitude of environmental pollution in this region, and a context in which to place archaeological findings. We observe initial evidence of anthropogenic lead (Pb) pollution during the earliest part of the Bronze Age [∼3,600 years before Common Era (BCE)], the earliest such evidence documented in European environmental records. A steady, almost linear increase in Pb concentration after 600 BCE, until ∼1,600 CE is observed, documenting the development in both sophistication and extent of southeastern European metallurgical activity throughout Antiquity and the medieval period. This provides an alternative view on the history of mineral exploitation in Europe, with metal-related pollution not ceasing at the fall of the western Roman Empire, as was the case in western Europe. Further comparison with other Pb pollution records indicates the amount of Pb deposited in the Balkans during the medieval period was, if not greater, at least similar to records located close to western European mining regions, suggestive of the key role the Balkans have played in mineral resource exploitation in Europe over the last 5,600 years. Copyright © 2018 the Author(s). Published by PNAS.
-
Contrast induced nephropathy: updated ESUR Contrast Media Safety Committee guidelines.
Stacul, Fulvio; van der Molen, Aart J; Reimer, Peter; Webb, Judith A W; Thomsen, Henrik S; Morcos, Sameh K; Almén, Torsten; Aspelin, Peter; Bellin, Marie-France; Clement, Olivier; Heinz-Peer, Gertraud
2011-12-01
The Contrast Media Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) has updated its 1999 guidelines on contrast medium-induced nephropathy (CIN). Topics reviewed include the definition of CIN, the choice of contrast medium, the prophylactic measures used to reduce the incidence of CIN, and the management of patients receiving metformin. Key Points • Definition, risk factors and prevention of contrast medium induced nephropathy are reviewed. • CIN risk is lower with intravenous than intra-arterial iodinated contrast medium. • eGFR of 45 ml/min/1.73 m (2) is CIN risk threshold for intravenous contrast medium. • Hydration with either saline or sodium bicarbonate reduces CIN incidence. • Patients with eGFR ≥ 60 ml/min/1.73 m (2) receiving contrast medium can continue metformin normally.
-
Clinical characteristics and predictive factors of subclinical diabetic nephropathy.
Zhang, Y; Yang, J; Zheng, M; Wang, Y; Ren, H; Xu, Y; Yang, Y; Cheng, J; Han, F; Yang, X; Chen, L; Shan, C; Chang, B
2015-02-01
To investigate the clinical characteristics and predictive factors of subclinical diabetic nephropathy in type 2 diabetes patients. A total of 298 type 2 diabetes patients were divided into 3 groups based on 24-h urinary microalbumin and estimated glomerular filtration rate: patients with normal albuminuria and glomerular filtration rate (NC), patients with normoalbuminuria and glomerular hyperfiltration (SDN) and patients with microalbuminuria (EDN). The renal size, tubular injury markers and ambulatory blood pressure were analyzed. Renal size increased in the SDN and EDN groups compared to the NC group (P<0.05), while renal length in the SDN group was greater than the EDN group (P<0.05). Patients in the SDN and EDN groups had higher level of urine retinol binding protein and N-acetyl-β-D-glucosaminidase and most of them developed proximal tubular dysfunction. The SDN group had higher 24-h mean and nocturnal diastolic blood pressure than the NC group (P<0.05), while the EDN group had higher systolic blood pressure and pulse pressure than the SDN group (P<0.01). More patients developed abnormal blood pressure rhythm in the SDN and EDN groups. The likelihood of a decrease in nocturnal systolic blood pressure was lower as the microalbuminuria increased. Increased renal size, more abnormal tubular injury markers and higher 24-h mean and nocturnal blood pressure were all risk factors of subclinical diabetic nephropathy. Patients with subclinical diabetic nephropathy had increased renal size, abnormal tubular injury markers, high blood pressure and abnormal circadian rhythm. © Georg Thieme Verlag KG Stuttgart · New York.
-
[Comparison of two rat models of IgA nephropathy].
Peng, Wei; Liu, Zheng-rong
2008-10-01
To study the methods for rapid establishment of rat models of IgA nephropathy. Forty female SD rats weighing 160-200 g were randomized into 3 groups. In group A, the rats received intravenous injection of staphylococcal enterotoxin B (SEB) and oral bovine serum albumin (BSA), and in group B, CCl4 was injected subcutaneously in addition to the above treatments; the rats in group C received no treatments to serve as the normal control group. The rats were sacrificed 10 and 14 weeks after the treatment for biochemical testing of the arterial blood and histopathological and IgA immunofluorescence examination of the renal tissues. The twenty-four-hour urine was collected at 10, 12, and 14 weeks after the treatments for detecting the urine proteins. Compared with the control group, the rats in groups A and B showed significantly increased serum creatinine, urine nitrogen and protein levels. Pathological examination of the renal tissue showed mild to moderate mesangial expansion and mesangial cell proliferation in groups A and B, without obvious difference between the two groups; but hematuria and proteinuria occurred earlier in group B with stronger IgA immunofluorescence than in group A. Both of the methods used in group A and group B can successfully induce IgA nephropathy in rats, but in group B, hematuria and urineprotein occurs earlier and IgA immunofluorescence is more stronger. Therefore intravenous SEB injection combined with oral BSA and subcutaneous CCl4 administration is a better method for time-efficient establishment of rat models of IgA nephropathy.
-
Clinical and genetic characterization of an autosomal dominant nephropathy.
Parvari, R; Shnaider, A; Basok, A; Katchko, L; Borochovich, Z; Kanis, A; Landau, D
2001-03-15
Autosomal dominant familial nephropathies with adult onset, no macroscopic cysts, and progressive deterioration include medullary cystic disease (ADMCKD) as well as other less specific entities. We studied a kindred of Jewish ancestry in which 15 members (both male and female) have suffered from chronic renal failure. The first evidence of renal involvement was observed between 18 and 38 years. It included hypertension followed by progressive renal insufficiency. No polyuria, anemia, gout, hematuria, nor proteinuria were seen. An average of 4.5 years elapsed from diagnosis to end-stage renal disease. Renal pathology at early stages of the disease showed extensive tubulointerstitial fibrosis and global glomerulosclerosis. Linkage analysis was performed at the two known loci of ADMCKD, on Chromosomes 1 and 16. Linkage to the chromosome 16 locus was excluded. However, linkage to the chromosome 1q21 locus of ADMCKD was established with a maximum two-point LOD score of 3.82 to D1S394. The disease interval could be narrowed to about 9 cM/7.4 Mb between D1S1156 and D1S2635. Multiple-point linkage analysis revealed a maximum LOD of 4.21, with a broad peak from markers D1S2858 and D1S2624. This report establishes linkage between a familial nephropathy characterized by hypertension and progressive renal failure to the locus described for ADMCKD, a disease classically associated with macroscopic corticomedullary cysts, salt-losing tubulointerstitial nephropathy, and anemia. This finding broadens the clinical spectrum of ADMCKD positioned on chromosome 1q21 locus. Copyright 2001 Wiley-Liss. Inc.
-
Guo, Taipin; Chen, Zukun; Tai, Xiantao; Liu, Zili; Zhu, Miansheng
2017-12-01
Some intractable chronic cough remains a common complaint for seeking medical care. Unexplained cough in lupus nephropathy patient is rare and therapeutic options are limited. A 57 year-old woman with a 7-year history of lupus nephropathy. She has suffered from chronic cough for 3 years accompanied with chronic low back pain and fatigue, as the conventional therapy cannot relieve the symptoms. The woman is diagnosed as intractable cough after lupus nephropathy. 9 times space-time acupuncture (STA) treatment was performed. The cough, as well as other uncomfortable symptoms like chronic low-back pain and fatigue have resolved, and no relapse for one year follow-up. STA may be an effective therapy to treat intractable chronic cough. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
-
Chronic myeloid leukemia in a child with IgA nephropathy.
Udani, Amish; Vijayakumar, Mahalingam; Prahlad, Nageswaran; Ekambaram, Sudha
2012-08-01
We report an 11 year old boy with IgA nephropathy developing chronic myeloid leukemia on follow-up. This association suggests that a B cell defect might be involved in the pathogenesis of these two conditions.
-
Aso, Yoshimasa; Takanashi, Keishi; Sekine, Kyouichi; Yoshida, Noboru; Takebayashi, Kohzo; Yoshihara, Kazuhiro; Inukai, Toshihiko
2004-08-01
It has been reported that the concentrations of both pyrraline and pentosidine, well-characterized advanced glycation end products, are increased in the urine of diabetic patients. To determine factors that influence the urinary excretion of pyrraline or pentosidine, we compared pyrraline or pentosidine concentrations with glycemic-control indexes, urinary albumin excretion, and urinary beta2-microglobulin in patients with type 2 diabetes. The study was conducted in 39 age-matched healthy control subjects and 50 diabetic patients, including 22 patients with normoalbuminuria, 15 with microalbuminuria, and 13 with macroalbuminuria. Both urinary pyrraline and pentosidine were measured in early-morning urine specimens with the use of high-pressure liquid chromatography. The urinary pentosidine concentration was significantly higher in diabetic patients than in control subjects (P <.01). In contrast, the urinary pyrraline concentration was significantly lower in diabetic patients than in control subjects (P <.001). Urinary pentosidine concentrations were greater in diabetic patients with macroalbuminuria and microalbuminuria than in those with normoalbuminuria. However, urinary pyrraline concentrations were significantly lower in diabetic patients with advanced nephropathy. Both the hemoglobin A(1c) (HbA(1c)) and the preceding year's mean HbA(1c) were lower in patients with macroalbuminuria than in those with normoalbuminuria or microalbuminuria. Urinary pyrraline, but not pentosidine, showed a significantly positive correlation with the preceding year's mean HbA(1c) (P<0.01). Multivariate analysis disclosed that urinary beta-2-microglobulin was independently correlated with the urinary concentrations of pentosidine and pyrraline (P <.05 for both). We conclude that the urinary concentration of pentosidine is greater in diabetic patients with overt nephropathy, whereas the urinary pyrraline concentration is significantly lower in diabetic patients with overt nephropathy
-
Endemism in the moss flora of North America.
Carter, Benjamin E; Shaw, Blanka; Shaw, A Jonathan
2016-04-01
Identifying regions of high endemism is a critical step toward understanding the mechanisms underlying diversification and establishing conservation priorities. Here, we identified regions of high moss endemism across North America. We also identified lineages that contribute disproportionately to endemism and document the progress of efforts to inventory the endemic flora. To understand the documentation of endemic moss diversity in North America, we tabulated species publication dates to document the progress of species discovery across the continent. We analyzed herbarium specimen data and distribution data from the Flora of North America project to delineate major regions of moss endemism. Finally, we surveyed the literature to assess the importance of intercontinental vs. within-continent diversification for generating endemic species. Three primary regions of endemism were identified and two of these were further divided into a total of nine subregions. Overall endemic richness has two peaks, one in northern California and the Pacific Northwest, and the other in the southern Appalachians. Description of new endemic species has risen steeply over the last few decades, especially in western North America. Among the few studies documenting sister species relationships of endemics, recent diversification appears to have played a larger role in western North America, than in the east. Our understanding of bryophyte endemism continues to grow rapidly. Large continent-wide data sets confirm early views on hotspots of endemic bryophyte richness and indicate a high rate of ongoing species discovery in North America. © 2016 Botanical Society of America.
-
Possible genetic defects in regulation of glycosaminoglycans in patients with diabetic nephropathy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Deckert, T.; Horowitz, I.M.; Kofoed-Enevoldsen, A.
1991-06-01
The hypothesis of genetic defects in glycosaminoglycan (GAG) regulation among patients with insulin-dependent diabetes mellitus (IDDM) and nephropathy was assessed by studies in tissue cultures of fibroblasts obtained from 7 patients with normal urinary albumin excretion, 11 patients with diabetic nephropathy, and 6 nondiabetic control subjects. The incorporation of (2H) glucosamine and (35S) sulfate into hyaluronic acid (HA), chondroitin sulfate and dermatan sulfate (CS + DS), and heparan sulfate (HS) was measured in cells, matrix, and medium and related to micrograms of tissue protein. Large interindividual variations were seen in all three groups, and the incorporation of (3H) glucosamine intomore » HA, CS + DS, and HS and (35S) sulfate into CS + DS and HS were not significantly different between the three groups. However, the fractional incorporation of (3H)glucosamine into HS was significantly reduced in diabetic patients with nephropathy compared with control subjects. This was the case not only when related to the total amount of GAGs (P = 0.014) but also when related to HA (P = 0.014). No significant difference was seen between control subjects and normoalbuminuric diabetic patients. The degree of N-sulfation of HS was not significantly different between the experimental groups. The results suggest that patients with diabetic nephropathy may suffer from deficiencies of coordinate regulation in the biosynthesis of GAG in fibroblasts, which may lead to a reduced density of HS in the extracellular matrix. If these changes reflect alterations in the biosynthesis of GAG from endothelial, myomedial, and mesangial cells, this observation may be relevant for the pathogenesis of severe diabetic complications.« less
-
Porcine/Chicken or Human Nephropathy as the Result of Joint Mycotoxins Interaction
Stoev, Stoycho D.; Denev, Stefan A.
2013-01-01
A survey was made of the literature concerning the occurrence and incidence of mycotoxic nephropathy in pigs and chicks in different countries. Various etiological factors contributing to the development of the disease were considered. The main nephrotoxic fungi as well as the specific conditions for their growth and toxins production were briefly described. A survey was made about the most frequent nephrotoxic fungal contaminants in various feedstuffs from plant origin. In addition, their natural quantities and importance for development of mycotoxic porcine/chick nephropathy (MPN/MCN) are also explored. In addition, a survey was made of the feedstuffs representing the most favorable environment for nephrotoxic fungal growth as well as the most favorable storehouse conditions for this fungal growth were shortly described. The significance of some underestimated fungal species, which can provoke kidney damage, was studied. The importance of joint mycotoxin interaction and newly identified fungal metabolites in the complex etiology of mycotoxic nephropathy ranged in some countries is deeply investigated. The toxicity of the low contamination levels of some combinations of mycotoxins often administered by pigs and chicks in the practice was carefully studied. PMID:24008340
-
ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy.
Rahimi, Zohreh
2012-10-01
Angiotensin converting enzyme (ACE) gene encodes ACE, a key component of renin angiotensin system (RAS), plays an important role in blood pressure homeostasis by generating the vasoconstrictor peptide angiotensin II. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. The presence of ACE insertion/deletion (I/D) polymorphism affects the plasma level of ACE. ACE DD genotype is associated with the highest systemic and renal ACE levels compared with the lowest ACE activity in carriers of II genotype. In this review focus has been performed on the study of ACE I/D polymorphism in various populations and its influence on the risk of onset and progression of diabetic nephropathy. Also, association between ACE I/D polymorphism and response to ACE inhibitor and angiotensin II receptor antagonists will be reviewed. Further, synergistic effect of this polymorphism and variants of some genes on the risk of development of diabetic nephropathy will be discussed.
-
Szymczak, Maciej; Kuźniar, Jakub; Kopeć, Wacław; Żabińska, Marcelina; Marchewka, Zofia; Kościelska-Kasprzak, Katarzyna; Klinger, Marian
2017-02-01
Heparanase is a β-glucuronidase that cleaves sugar chains of heparan sulfate proteoglycans. It is believed that heparanase may be involved in the pathogenesis of proteinuria. The aim of this study was to assess the significance of heparanase in the pathogenesis of particular glomerulonephritis types. The evaluation of heparanase activity in serum, urine, and granulocytes and superoxide dismutase (SOD) activity in granulocytes of patients with lupus nephritis (n = 17), membranous nephropathy (n = 11), IgA nephropathy (n = 12), focal and segmental glomerulosclerosis (n = 18), mesangiocapillary glomerulonephritis (n = 12) and in 19 healthy volunteers were performed. The heparanase activity in granulocytes of patients with lupus nephritis and membranous nephropathy was higher than heparanase activity in granulocytes in the control group (p = 0.02 in both cases). This is the first observation of this phenomenon. There was no difference between SOD activity in granulocytes of patients with all assessed types of glomerulonephritis and the control group. A positive correlation between heparanase activity in urine and double-strain DNA antibodies (r = 0.51; p = 0.04), and reverse correlations between heparanase in urine and hemolytic activity of the complement (r = -0.57; p = 0.03) in the lupus nephritis group, and between heparanase activity in granulocytes and serum total protein level (r = -0.69; p = 0.02) in membranous nephropathy were observed. Increase in heparanase activity without changes in superoxide dismutase activity in the granulocytes from patients with lupus nephritis and membranous nephropathy was observed. It may be used as one of the markers of these disease activities.
-
Du, Pengchao; Fan, Baoxia; Han, Huirong; Zhen, Junhui; Shang, Jin; Wang, Xiaojie; Li, Xiang; Shi, Weichen; Tang, Wei; Bao, Chanchan; Wang, Ziying; Zhang, Yan; Zhang, Bin; Wei, Xinbing; Yi, Fan
2013-08-01
An increasing number of clinical and animal model studies indicate that activation of the innate immune system and inflammatory mechanisms are important in the pathogenesis of diabetic nephropathy. Nucleotide-binding oligomerization domain containing 2 (NOD2), a member of the NOD-like receptor family, plays an important role in innate immune response. Here we explore the contribution of NOD2 to the pathogenesis of diabetic nephropathy and found that it was upregulated in kidney biopsies from diabetic patients and high-fat diet/streptozotocin-induced diabetic mice. Further, NOD2 deficiency ameliorated renal injury in diabetic mice. In vitro, NOD2 induced proinflammatory response and impaired insulin signaling and insulin-induced glucose uptake in podocytes. Moreover, podocytes treated with high glucose, advanced glycation end-products, tumor necrosis factor-α, or transforming growth factor-β (common detrimental factors in diabetic nephropathy) significantly increased NOD2 expression. NOD2 knockout diabetic mice were protected from the hyperglycemia-induced reduction in nephrin expression. Further, knockdown of NOD2 expression attenuated high glucose-induced nephrin downregulation in vitro, supporting an essential role of NOD2 in mediating hyperglycemia-induced podocyte dysfunction. Thus, NOD2 is one of the critical components of a signal transduction pathway that links renal injury to inflammation and podocyte insulin resistance in diabetic nephropathy.
-
Zhang, Lei; Li, Yin; Guo, Xinfeng; May, Brian H.; Xue, Charlie C. L.; Yang, Lihong; Liu, Xusheng
2014-01-01
Objectives. To apply modern text-mining methods to identify candidate herbs and formulae for the treatment of diabetic nephropathy. Methods. The method we developed includes three steps: (1) identification of candidate ancient terms; (2) systemic search and assessment of medical records written in classical Chinese; (3) preliminary evaluation of the effect and safety of candidates. Results. Ancient terms Xia Xiao, Shen Xiao, and Xiao Shen were determined as the most likely to correspond with diabetic nephropathy and used in text mining. A total of 80 Chinese formulae for treating conditions congruent with diabetic nephropathy recorded in medical books from Tang Dynasty to Qing Dynasty were collected. Sao si tang (also called Reeling Silk Decoction) was chosen to show the process of preliminary evaluation of the candidates. It had promising potential for development as new agent for the treatment of diabetic nephropathy. However, further investigations about the safety to patients with renal insufficiency are still needed. Conclusions. The methods developed in this study offer a targeted approach to identifying traditional herbs and/or formulae as candidates for further investigation in the search for new drugs for modern disease. However, more effort is still required to improve our techniques, especially with regard to compound formulae. PMID:24744808
-
Immunoglobulin A Nephropathy: Advances in Understanding of Pathogenesis and Treatment.
Lafayette, Richard A; Kelepouris, Ellie
2018-05-31
Immunoglobulin A (IgA) nephropathy is the most common form of primary glomerulonephritis and has clinical associations with a wide range of inflammatory and infectious diseases. There is a substantial variation in clinical course and outcomes, with many patients not diagnosed until they present with sequelae, which may include gross hematuria, hypertension, renal insufficiency, and/or significant proteinuria. Treatment options are currently limited and directed mainly toward control of these sequelae and have limited ability to reduce the incidence of end-stage renal disease or treat the primary IgA defect. Growing knowledge about the pathogenesis of IgA nephropathy and research into its genetic basis are helping to elucidate the course of this widely variable disease. IgA accumulation in the kidneys is thought to be the result of a number of different pathways in a "multi-hit" process that includes an initial traumatic trigger (often infection related) and subsequent memory responses that are amplified in those with a genetic predisposition to the disease and lead to an inflammatory response in susceptible individuals. Genome-wide association studies are providing new insights into the genetic variance of this autoimmune disease and are yielding information that may address both its causes and consequences. Key Messages: New treatment approaches are urgently required for the management of patients with IgA nephropathy. Novel interventions based around its inflammatory nature and "multi-hit" pathogenesis are being investigated to potentially limit disease progression. © 2018 S. Karger AG, Basel.
-
Lei, Xiao; Zhang, Bo-da; Ren, Ji-Gang; Luo, Fang-Li
2018-05-21
Apoptosis of podocytes plays a crucial role in diabetic nephropathy (DN) development, and astragaloside (AS-IV) has a significant impact on podocyte apoptosis. This study aims to explore the effect of AS-IV on diabetic nephropathy progression. The diabetic nephropathy model was established in rats with streptozotocin (STZ) injection. The albuminuria was examined by using the enzyme linked immunosorbent assay (ELISA). The expression of miR-378, tumor-necrosis factor (TNF) receptor (TNFR)-associated factor 5 (TRAF5) mRNA and protein was analyzed by qRT-PCR and western blot, respectively. Cell transfection was conducted for modulating endogenous expression of miR-378. Dual luciferase reporter assay was used to evaluate the interaction between miR-378 and TRAF5. The terminal deoxynucleotidy transferase dUTP nick end labeling (TUNEL) staining assay was performed for apoptosis detection. AS-IV protected diabetic rats from developing into diabetic nephropathy. The expression of miR-378 was down-regulated in diabetic nephropathy rats, which was reversed by AS-IV. AS-IV enhanced the expression of miR-378 in podocytes treated with high glucose. MiR-378 negatively regulated TRAF5. AS-IV inhibited the expression of TRAF5 through miR-378. AS-IV suppressed apoptosis of podocytes via targeting miR-378. AS-IV suppresses apoptosis of the podocytes through the miR-378/TRAF5 signaling pathway, and thereby repressing diabetic nephropathy development. Copyright © 2017. Published by Elsevier Inc.
-
Aver'ianov, A P; Tkacheva, E N; Bolotova, N V; Filina, N Iu; Ivanova, Iu V; Nikolaeva, N V; Tikhonova, L A
2011-01-01
The present study included 86 children aged between 7 and 17 years with type 1 diabetes mellitus from 1 to 15 years in duration. In all the patients, renal blood flow was investigated with the use of ultrasonic dopplerography. The results of the study suggest disturbances of intrarenal hemodynamics that manifested themselves as enhanced resistance of renal arteries from periphery to the centre in the patients at the hyperfiltration stage of diabetic nephropathy (DN) in conjunction with the reduced velocity of blood flow in inter-lobular and segmental arteries. In contrast, the patients at the microalbuminuric stage of diabetic nephropathy exhibited increased resistance and reduced velocity of blood flow in the main renal veins. In 35 patients presenting with diabetic nephropathy, hemodynamic correction was achieved by the application of the traveling pulsed magnetic field (TP-MF) to the renal region using an AMO-ATOS-E apparatus (Russia). This treatment resulted in normalization of the characteristics of renal blood flow. It is concluded that TPMF has good prospects for the use as a component of the combined treatment of diabetic nephropathy.
-
Klarić, Irena Martinović; Salihović, Marijana Pericić; Lauc, Lovorka Barać; Zhivotovsky, Lev A; Rootsi, Siiri; Janićijević, Branka
2009-03-01
The Bayash are a branch of Romanian speaking Roma living dispersedly in Central, Eastern, and Southeastern Europe. To better understand the molecular architecture and origin of the Croatian Bayash paternal gene pool, 151 Bayash Y chromosomes were analyzed for 16 SNPs and 17 STRs and compared with European Romani and non-Romani majority populations from Europe, Turkey, and South Asia. Two main layers of Bayash paternal gene pool were identified: ancestral (Indian) and recent (European). The reduced diversity and expansion signals of H1a patrilineages imply descent from closely related paternal ancestors who could have settled in the Indian subcontinent, possibly as early as between the eighth and tenth centuries AD. The recent layer of the Bayash paternal pool is dominated by a specific subset of E1b1b1a lineages that are not found in the Balkan majority populations. At least two private mutational events occurred in the Bayash during their migrations from the southern Balkans toward Romania. Additional admixture, evident in the low frequencies of typical European haplogroups, J2, R1a, I1, R1b1b2, G, and I2a, took place primarily during the early Bayash settlement in the Balkans and the Romani bondage in Romania. Our results indicate two phenomena in the Bayash and analyzed Roma: a significant preservation of ancestral H1a haplotypes as a result of considerable, but variable level of endogamy and isolation and differential distribution of less frequent, but typical European lineages due to different patterns of the early demographic history in Europe marked by differential admixture and genetic drift. (c) 2008 Wiley-Liss, Inc.
-
Cancer Risk after Cyclophosphamide Treatment in Idiopathic Membranous Nephropathy
van Dijk, Peter R.; Hofstra, Julia M.; Wetzels, Jack F.M.
2014-01-01
Background and objectives Cyclophosphamide treatment improves renal survival in patients with idiopathic membranous nephropathy. However, use of cyclophosphamide is associated with cancer. The incidence of malignancies in patients with idiopathic membranous nephropathy was evaluated, and the cancer risk associated with cyclophosphamide use was estimated. Design, setting, participants, & measurements Patients who attended the clinic were included prospectively from 1995 on. A crude incidence ratio for the occurrence of malignancy was calculated. Incidence ratios were subsequently standardized to potential confounders. Latency between cyclophosphamide therapy and the occurrence of cancer was estimated by stratifying for time since the start of treatment. Finally, Poisson regression was used to obtain a multiple adjusted incidence ratio and investigate the dose–response relationship between cyclophosphamide and cancer. Results Data were available for 272 patients; the mean age was 51 years, and 70% of the patients were men. Median follow-up was 6.0 years (interquartile range=3.6–9.5), and 127 patients were treated with cyclophosphamide. Cancer incidence was 21.2 per 1000 person-years in treated patients compared with 4.6 per 1000 person-years in patients who did not receive cyclophosphamide, resulting in crude and adjusted incidence ratios of 4.6 (95% confidence interval, 1.5 to 18.8) and 3.2 (95% confidence interval, 1.0 to 9.5), respectively. Conclusion Cyclophosphamide therapy in idiopathic membranous nephropathy gives a threefold increase in cancer risk. For the average patient, this finding translates into an increase in annual risk from approximately 0.3% to 1.0%. The increased risk of malignancy must be balanced against the improved renal survival. PMID:24855280
-
Acute histopathological changes produced by Penicillium aurantiogriseum nephrotoxin in the rat.
Adatia, R.; Heaton, J. M.; Macgeorge, K. M.; Mantle, P. G.
1991-01-01
Shredded wheat moulded by an isolate of Penicillium aurantiogriseum elicited progressive histopathological changes at the rat renal cortico-medullary junction during 5 days of dosing, when incorporated into diet as a 20% component. The changes of acute tubular necrosis and regeneration were seen in the P3 segment of the nephron. In rats exposed to contaminated diet for 5 days the histopathological changes regressed in severity by about one-half within a further 4 days on normal diet and by 7 days the tubular epithelium was nearly normal. A partially purified fraction of an alcohol extract, selected by preparative high-voltage electrophoresis and anion exchange and notably rich in amino-compounds, was typically nephrotoxic when given in diet over 4 days. Acute marked tubular necrosis also occurred when the same fraction was given intraperitoneally over a similar period. The acute histological changes provide a rapid bioassay for this Penicillium nephrotoxicity and facilitate the search for the toxic metabolite(s). The cumulative expression of necrosis and repair over only a few days in tubular epithelium suggests that chronic exposure will elicit a more complex pathology which might serve as an experimental model for the idiopathic Balkan endemic nephropathy. Images Fig. 1 p51-a Fig. 2 PMID:1888665
-
Wang, Yinan; Chan, Wan
2014-06-25
Nephrotoxic and carcinogenic aristolochic acids (AAs) are naturally occurring nitrophenanthrene carboxylic acids in the herbal genus Aristolochia. The misuse of AA-containing herbs in preparing slimming drugs has caused hundred of cases of kidney disease in Belgium women in a slimming regime in the early 1990s. Accumulating evidence also suggested that prolong dietary intake of AA-contaminated food is one of the major causes to the Balkan endemic nephropathy that was first observed in the late 1950s. Therefore, analytical methods of high sensitivity are extremely important for safeguarding human exposure to AA-containing herbal medicines, herbal remedies, and food composites. In this paper, we describe the development of a new high-performance liquid chromatography coupled fluorescence detector (HPLC-FLD) method for the sensitive determination of AAs. The method makes use of a novel cysteine-induced denitration reaction that "turns on" the fluorescence of AAs for fluorometric detections. Our results showed that the combination of cysteine-induced denitration and HPLC-FLD analysis allows for sensitive quantification of AA-I and AA-II at detection limits of 27.1 and 25.4 ng/g, respectively. The method was validated and has been successfully applied in quantifying AAs in Chinese herbal medicines.
-
Occurrence of ochratoxin A in spices commercialized in Abidjan (Côte d'Ivoire).
Manda, Pierre; Adanou, Ketty Michele; Ardjouma, Dembelé; Adepo, Aholia Jean Baptiste; Dano, Djédjé Sébastien
2016-08-01
Ochratoxin A (OTA) is a mycotoxin produced mostly by several species of Aspergillus and Penicillium. OTA is nephrotoxic in all animal species in which it has been tested and is cancerogenic in rodents. It is associated with Balkan endemic nephropathy. It is naturally present in many crop products such as cereals (barley, wheat, maize) and dried fruits, spices, coffee, wine, olives, and cocoa. The aim of this study was to assess the contamination of three Ivoirian spices with OTA (ginger, chili, and pepper) widely consumed by the population. A total of 90 spice samples (ginger: n = 30; chili: n = 30; pepper n = 30) was taken from various sales outlets of Abidjan. OTA was quantified using an HPLC apparatus coupled with a fluorimetric detector. The chili and ginger samples were contaminated with OTA at a mean concentration of 57.48 ± 174 and 0.12 ± 0.15 μg/kg, respectively. No contamination of the pepper samples was detected. Eight (26.67 %) of the chili samples exceeded the maximum limit of 15 μg/kg established by European regulation. These results should serve as an alert on the risk to the consumer population of these products that are highly contaminated with OTA.
-
NASA Astrophysics Data System (ADS)
Dyulgerov, Momchil; Ovtcharova-Schaltegger, Maria; Ulianov, Alexey; Schaltegger, Urs
2018-06-01
The Variscan orogen in southeast Europe is exposed in isolated remnants, affected by a subsequent Alpine tectono-magmatic overprint. Unlike the central European Variscides, in SE Europe the juxtaposition and correlation of the events and products are impeded by the scarcity of Variscan domains with preserved magmatic, metamorphic, sedimentological and structural characteristics. To reveal the particular evolution of the Variscan orogen in Balkan Mts, we present the results of ID-TIMS and LA-ICP-MS dating of three potassic-alkaline intrusions: Svidnya, Buhovo-Seslavtsi and Shipka. The age determinations from the plutons do not permit to establish their unequivocal ages, but they bracket the time interval of emplacements. Based on geochronological, tectonic and stratigraphic evidence the emplacement interval for plutons could be: 317-310 Ma for Svidnya, 330-310 Ma for Buhovo-Seslavtsi and 320-303 Ma for Shipka. These results show that the generation of potassic-alkaline magmas was post-Visean and is contemporaneous with the adjacent numerous calc-alkaline granitoid plutons. Thus, the Variscan orogen in the Balkan Mts is not characterized by a time-dependent geochemical evolution of magma generation. Hence, the observed differences in the rocks' compositions can be interpreted solely by distinction between the magma sources. The available data for both potassic-alkaline and calc-alkaline rocks indicate that the major episodes of crustal stacking and shearing in the Balkan part of the Variscan edifice are pre-Visean ( 330 Ma). The present study reveals that the potassic-alkaline rocks from the Balkan Mts are younger than the central European potassic granitoids (durbachites). It suggests that melting of enriched mantle source took place at different times throughout the Variscan orogen. In spite of the alkaline character of the magmas, the studied zircons show a complex nature, with inherited cores and magmatic overgrowths. The observed heterogeneities in the zircons
-
Díaz-López, Andrés; Babio, Nancy; Martínez-González, Miguel A; Corella, Dolores; Amor, Antonio J; Fitó, Montse; Estruch, Ramon; Arós, Fernando; Gómez-Gracia, Enrique; Fiol, Miquel; Lapetra, José; Serra-Majem, Lluís; Basora, Josep; Basterra-Gortari, F Javier; Zanon-Moreno, Vicente; Muñoz, Miguel Ángel; Salas-Salvadó, Jordi
2015-11-01
To date no clinical trials have evaluated the role of dietary patterns on the incidence of microvascular diabetes complications. We hypothesized that a nutritional intervention based on the Mediterranean diet (MedDiet) would have greater protective effect on diabetic retinopathy and nephropathy than a low-fat control diet. This was a post hoc analysis of a cohort of patients with type 2 diabetes participating in the PREvención con DIeta MEDiterránea (PREDIMED) study, a multicenter randomized nutritional intervention trial conducted in a population at high cardiovascular risk. Individuals with type 2 diabetes who were free of microvascular complications at enrollment (n = 3,614, aged 55-80 years) were randomly assigned to one of three dietary interventions: MedDiet supplemented with extravirgin olive oil (MedDiet+EVOO), MedDiet supplemented with mixed nuts (MedDiet+Nuts), or a low-fat control diet. Two independent outcomes were considered: new onset of diabetic retinopathy and nephropathy. Hazard ratios (HRs) were calculated using multivariable-adjusted Cox regression. During a median follow-up of 6.0 years, we identified 74 new cases of retinopathy and 168 of nephropathy. Compared with the control diet, multivariable-adjusted HRs for diabetic retinopathy were 0.56 (95% CI 0.32-0.97) for the MedDiet+EVOO and 0.63 (0.35-1.11) for the MedDiet+Nuts. No between-group differences were found for nephropathy. When the yearly updated information on adherence to the MedDiet was considered, the HR for retinopathy in the highest versus the lowest quintile was 0.34 (0.13-0.89; P = 0.001 for trend). No significant associations were found for nephropathy. A MedDiet enriched with EVOO may protect against diabetic retinopathy but not diabetic nephropathy. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
-
Barbieri, Lucia; Verdoia, Monica; Marino, Paolo; Suryapranata, Harry; De Luca, Giuseppe
2016-06-01
Contrast-induced nephropathy is a common complication of procedures that are likely to use contrast media. The identification of high-risk patients and preventive optimal hydration are key measures to reduce the incidence of contrast-induced nephropathy. The aim of this study was to evaluate the role of the contrast volume to creatinine clearance ratio (V/CrCl) in the prediction of contrast-induced nephropathy after coronary angiography or percutaneous coronary intervention. Our population consisted of 2308 consecutive patients undergoing coronary angiography and/or percutaneous coronary intervention. The risk of contrast-induced nephropathy was evaluated across quartiles of the V/CrCl. Receiver operating characteristic curves were used to identify the best predictive value. Contrast-induced nephropathy was defined as an absolute increase of 0.5 mg/dL or a relative increase of >25% in creatinine levels 24-48 hours after the procedure. The total incidence of contrast-induced nephropathy was 12.2% and was significantly higher in the fourth quartile (first quartile 8.8%, second quartile 8.9%, third quartile 11.6% and fourth quartile 19.4%; P < 0.001). Using receiver operating characteristic curves we identified V/CrCl ≥ 6.15 as the best discriminant value for the prediction of contrast-induced nephropathy, which occurred in 25.1% of patients with V/CrCl ≥ 6.15 versus 9.7% in patients with V/CrCl < 6.15. These results were also confirmed at multivariate analysis after correction for all baseline confounders (adjusted odds ratio (AOR) (95% confidence interval (CI)) 1.81 (1.19-2.76); P = 0.005). The association between V/CrCl > 6.15 and an increased risk of contrast-induced nephropathy was confirmed among diabetic (11% vs. 27.7%; p P < 0.001) and non-diabetic patients (8.9% vs. 23%; Pp < 0.001), also after correction for all baseline confounders. This is one of the largest studies evaluating the association between the V/CrCl ratio
-
All That Glitters Yellow Is Not Gold: Presentation and Pathophysiology of Bile Cast Nephropathy.
Pitlick, Mitchell; Rastogi, Prerna
2017-10-01
Acute kidney injury (AKI) often manifests in patients with liver disease because of a prerenal cause and presents as acute tubular necrosis or hepatorenal syndrome. Distinguishing between these entities is important for prognosis and treatment. Some patients may develop AKI related to their underlying liver disease: for example, membranoproliferative glomerulonephritis or IgA nephropathy. Bile cast nephropathy is an often ignored differential diagnosis of AKI in the setting of obstructive jaundice. It is characterized by the presence of bile casts in renal tubules, which can possibly cause tubular injury through obstructive and direct toxic effects. Thus, AKI in patients with liver disease may have a structural component in addition to a functional one. In this study, we describe 2 patients with severe hyperbilirubinemia who developed AKI and underwent a kidney biopsy that revealed bile casts in tubular lumens, consistent with bile cast nephropathy. One patient was treated aggressively for alcoholic hepatitis and required hemodialysis for AKI. The second patient was treated conservatively for drug-induced liver injury and did not require dialysis. Both patients saw a reduction in their bilirubin and creatinine toward baseline. Bile cast nephropathy is an important pathological entity that may account for the renal dysfunction in some patients with liver disease. It requires kidney biopsy for diagnosis and may often be overlooked given the scarcity of kidney biopsy in this particular clinical setting. The etiology is multifactorial, and it is often difficult to predict without the aid of a renal biopsy.
-
Isolated heart and liver transplant recipients are at low risk for polyomavirus BKV nephropathy.
Puliyanda, Dechu P; Amet, Nurmamet; Dhawan, Archana; Hilo, Lara; Radha, Raju K; Bunnapradist, Suphamai; Czer, Lawrence; Martin, Paul; Jordan, Stanley; Toyoda, Mieko
2006-01-01
BKV infection and nephropathy is a significant cause of allograft dysfunction in kidney transplantation. BKV viremia, rather than viruria, corresponds to BKV nephropathy. The prevalence of BKV viremia in non-renal solid organ transplants has not been systematically evaluated. We determined prevalence of BKV viremia in kidney, combined kidney-heart, kidney-liver, kidney-pancreas, kidney-heart-liver, and heart and liver transplant recipients using BKV-PCR. Seven out of 173 (4%) kidney transplant recipients had BKV viremia, with BKV>2 x 10(5) copies/mL in 6/7 and 1.9 x 10(3) in the remaining one patient. BKV viremia was not found in 24 heart transplant recipients, whereas 1/37 (2.7%) liver transplants showed low copy numbers (< or =10(3)). BKV-PCR< or =10(3) copies/mL were also found in one of each combined kidney-heart and kidney-liver transplant recipients. BKV nephropathy was proven by biopsy in 4/6 patients with high BKV viral loads. All six patients showed renal dysfunction, requiring reduction in immunosuppression and antiviral therapy. All four patients with low BKV viral loads (1.9 x 10(3) or < or =10(3)) showed stable renal function after reduction of immunosuppression or no treatment, respectively. Higher BKV levels in plasma are associated with renal dysfunction. Kidney transplant recipients are at high risk compared with recipients of isolated heart or liver allografts, for development of BKV nephropathy.
-
Desai, Sachin N; Akalu, Zenebe; Teferi, Mekonnen; Manna, Byomkesh; Teshome, Samuel; Park, Ju Yeon; Yang, Jae Seung; Kim, Deok Ryun; Kanungo, Suman; Digilio, Laura
2016-02-01
Studies on safety, immunogenicity and efficacy of the killed, bivalent whole cell oral cholera vaccine (Shanchol) have been conducted in historically endemic settings of Asia. Recent cholera vaccination campaigns in Haiti and Guinea have also demonstrated favourable immunogenicity and effectiveness in nonendemic outbreak settings. We performed a secondary analysis, comparing immune responses of Shanchol from two randomised controlled trials performed in an endemic and a less endemic area (Addis Ababa) during a nonoutbreak setting. While Shanchol may offer some degree of immediate protection in primed populations living in cholera endemic areas, as well as being highly immunogenic in less endemic settings, understanding the characteristics of immune responses in each of these areas is vital in determining ideal dosing strategies that offer the greatest public health impact to populations from areas with varying degrees of cholera endemicity. © 2015 John Wiley & Sons Ltd.
-
Lee, Dae-Yeol; Kim, Sun-Young; Jo, Dae-Sun; Hwang, Pyoung Han; Kang, Kyung Pyo; Lee, Sik; Kim, Won; Park, Sung Kwang
2006-07-01
Ghrelin is a novel peptide hormone, which exerts somatotropic, orexigenic and adipogenic effects. Recent studies have shown that the preproghrelin Leu72Met polymorphism is associated with serum creatinine (Scr) concentration in type 2 diabetes; 72Met carriers exhibited lower Scr levels as compared with the 72Met non-carriers. We hypothesized that the preproghrelin Leu72Met polymorphism is associated with a lower rate of developing renal dysfunction in patients with type 2 diabetic nephropathy. The preproghrelin Leu72Met polymorphism was investigated using PCR techniques in 138 patients with diabetic nephropathy divided into two groups, one with normal renal function and the other with renal dysfunction. Determination of the frequency of the preproghrelin Leu72Met polymorphism was the main outcome measure. The frequency of the Leu72Met polymorphism in diabetic nephropathy was significantly lower in patients with renal dysfunction (15.9%, P < 0.01) than in patients with normal renal function (42.0%) or in the diabetes control group (40.6%). The Leu72Met polymorphism was also associated with serum total cholesterol levels in diabetic nephropathy patients with renal dysfunction; the 72Met carriers had lower total cholesterol levels than the 72Met non-carriers (P < 0.05). These data suggest that 72Met carrier status may be used as a marker predicting a lower chance of developing renal dysfunction in diabetic nephropathy.
-
Lin, Xu; You, Yanwu; Wang, Jie; Qin, Youling; Huang, Peng; Yang, Fafen
2015-04-01
MiR-155 has been reported to be involved in both innate and adaptive immune responses. But the role of miR-155 in hyperglycemia-induced nephropathy is still unknown. In our current study, 3-month-old male wild-type C57 mice and Mir-155(-/-) mice were used to establish hyperglycemia-induced nephropathy. In our hyperglycemia-induced nephropathy model, the expression of podocyte injury marker desmin was markedly increased in the diabetes group when compared with control. Diabetes also significantly decreased the levels of nephrin and acetylated nephrin, whereas the expression of miR-155 was markedly increased in diabetes group when compared with control. MiR-155(-/-) mice showed significantly increased expression of nephrin, acetylated nephrin, and Wilm's tumor-1 protein (WT-1) when compared with wild-type control. MiR-155 deficiency results in significantly decrease in IL-17A expression both in vivo and in vitro. And the increased expression of WT-1, nephrin, and ac-nephrin was reversed with additional treatment of rmIL-17. Furthermore, we found that the inhibited Th17 differentiation induced by miR-155 deficiency was dependent on increased expression of SOCS1. In conclusion, miR-155 deficiency promotes nephrin acetylation and attenuates renal damage in hyperglycemia-induced nephropathy. This was associated with inhibited IL-17 production through enhancement of SOCS1 expression.
-
Informal Patient Payments and Bought and Brought Goods in the Western Balkans – A Scoping Review
Buch Mejsner, Sofie; Eklund Karlsson, Leena
2017-01-01
Introduction: Informal patient payments for healthcare are common in the Western Balkans, negatively affecting public health and healthcare. Aim: To identify literature from the Western Balkans on what is known about informal patient payments and bought and brought goods, to examine their effects on healthcare and to determine what actions can be taken to tackle these payments. Methods: After conducting a scoping review that involved searching websites and databases and filtering with eligibility criteria and quality assessment tools, 24 relevant studies were revealed. The data were synthesized using a narrative approach that identified key concepts, types of evidence, and research gaps. Results: The number of studies of informal patient payments increased between 2002 and 2015, but evidence regarding the issues of concern is scattered across various countries. Research has reported incidents of informal patient payments on a wide scale and has described various patterns and characteristics of these payments. Although these payments have typically been small – particularly to providers in common areas of specialized medicine – evidence regarding bought and brought goods remains limited, indicating that such practices are likely even more common, of greater magnitude and perhaps more problematic than informal patient payments. Only scant research has examined the measures that are used to tackle informal patient payments. The evidence indicates that legalizing informal patient payments, introducing performance-based payment systems, strengthening reporting, changing mentalities and involving the media and the European Union (EU) or religious organizations in anti-corruption campaigns are understood as some of the possible remedies that might help reduce informal patient payments. Conclusion: Despite comprehensive evidence regarding informal patient payments, data remain scattered and contradictory, implying that informal patient payments are a complex phenomenon
-
ERIC Educational Resources Information Center
Jelavich, Barbara
Principal issues in the 20th century development of the Balkan Peninsula are discussed in this introductory history text. Three themes--national rivalries, great power interference, and the economic, social, and political problems of modernization--are given special emphasis. An overview of 18th and 19th century history precedes the two major…
-
Delimiting Areas of Endemism through Kernel Interpolation
Oliveira, Ubirajara; Brescovit, Antonio D.; Santos, Adalberto J.
2015-01-01
We propose a new approach for identification of areas of endemism, the Geographical Interpolation of Endemism (GIE), based on kernel spatial interpolation. This method differs from others in being independent of grid cells. This new approach is based on estimating the overlap between the distribution of species through a kernel interpolation of centroids of species distribution and areas of influence defined from the distance between the centroid and the farthest point of occurrence of each species. We used this method to delimit areas of endemism of spiders from Brazil. To assess the effectiveness of GIE, we analyzed the same data using Parsimony Analysis of Endemism and NDM and compared the areas identified through each method. The analyses using GIE identified 101 areas of endemism of spiders in Brazil GIE demonstrated to be effective in identifying areas of endemism in multiple scales, with fuzzy edges and supported by more synendemic species than in the other methods. The areas of endemism identified with GIE were generally congruent with those identified for other taxonomic groups, suggesting that common processes can be responsible for the origin and maintenance of these biogeographic units. PMID:25611971
-
Non-endemic cases of lymphatic filariasis.
Jones, Robert T
2014-11-01
Several cases of lymphatic filariasis (LF) have been reported in non-endemic countries due to travellers, military personnel and expatriates spending time in and returning from endemic areas, as well as immigrants coming from these regions. These cases are reviewed to assess the scale and context of non-endemic presentations and to consider the biological factors underlying their relative paucity. Cases reported in the English, French, Spanish and Portuguese literature during the last 30 years were examined through a search of the PubMed, ProMED-mail and TropNet resources. The literature research revealed 11 cases of lymphatic filariasis being reported in non-endemic areas. The extent of further infections in recent migrants to non-endemic countries was also revealed through the published literature. The life-cycle requirements of Wuchereria and Brugia species limit the extent of transmission of LF outside of tropical regions. However, until elimination, programmes are successful in managing the disease, there remains a possibility of low rates of infection being reported in non-endemic areas, and increased international travel can only contribute to this phenomenon. Physicians need to be aware of the signs and symptoms of lymphatic filariasis, and infection should be considered in the differential diagnosis of people with a relevant travel history. © 2014 John Wiley & Sons Ltd.
-
Pathak, Jahnavi V; Dass, Ervilla E
2015-01-01
Till date, several studies have compared angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in terms of delaying the progression of diabetic nephropathy. But the superiority of one drug class over the other remains unsettled. This study has retrospectively compared the effects of ACE inhibitors and ARBs in diabetic nephropathy. The study aims to compare ACE inhibitors and ARBs in terms of delaying or preventing the progression of diabetic nephropathy, association between blood pressure (B.P) and urinary albumin and also B.P and serum creatinine with ACE inhibitor and ARB, know the percentage of hyperkalemia in patients of diabetic nephropathy receiving ACE inhibitor or ARB. A total of 134 patients diagnosed with diabetic nephropathy during the years 2001-2010 and having a complete follow-up were studied, out of which 99 were on ARB (63 patients of Losartan and 36 of Telmisartan) and 35 on ACE inhibitor (Ramipril). There was at least 1-month of interval between each observation made and also between the date of treatment started and the first reading that is, the observation of the 1(st) month. In total, three readings were taken that is, of the 1(st), 2(nd) and 3(rd) month after the treatment started. Comparison of the 1(st) and 3(rd) month after the treatment started was done. Mean ± standard deviation, Paired t-test, and Chi-square were used for the analysis of the data. The results reflect that ARBs (Losartan and Telmisartan) when compared to ACE inhibitor (Ramipril) are more effective in terms of delaying the progression of diabetic nephropathy and also in providing renoprotection. Also, ARBs have the property of simultaneously decreasing the systolic B.P and albuminuria when compared to ACE inhibitor (Ramipril). Angiotensin receptor blockers are more renoprotective than ACE inhibitors and also provide better cardioprotection.
-
Role of mTOR in podocyte function and diabetic nephropathy in humans and mice
Gödel, Markus; Hartleben, Björn; Herbach, Nadja; Liu, Shuya; Zschiedrich, Stefan; Lu, Shun; Debreczeni-Mór, Andrea; Lindenmeyer, Maja T.; Rastaldi, Maria-Pia; Hartleben, Götz; Wiech, Thorsten; Fornoni, Alessia; Nelson, Robert G.; Kretzler, Matthias; Wanke, Rüdiger; Pavenstädt, Hermann; Kerjaschki, Dontscho; Cohen, Clemens D.; Hall, Michael N.; Rüegg, Markus A.; Inoki, Ken; Walz, Gerd; Huber, Tobias B.
2011-01-01
Chronic glomerular diseases, associated with renal failure and cardiovascular morbidity, represent a major health issue. However, they remain poorly understood. Here we have reported that tightly controlled mTOR activity was crucial to maintaining glomerular podocyte function, while dysregulation of mTOR facilitated glomerular diseases. Genetic deletion of mTOR complex 1 (mTORC1) in mouse podocytes induced proteinuria and progressive glomerulosclerosis. Furthermore, simultaneous deletion of both mTORC1 and mTORC2 from mouse podocytes aggravated the glomerular lesions, revealing the importance of both mTOR complexes for podocyte homeostasis. In contrast, increased mTOR activity accompanied human diabetic nephropathy, characterized by early glomerular hypertrophy and hyperfiltration. Curtailing mTORC1 signaling in mice by genetically reducing mTORC1 copy number in podocytes prevented glomerulosclerosis and significantly ameliorated the progression of glomerular disease in diabetic nephropathy. These results demonstrate the requirement for tightly balanced mTOR activity in podocyte homeostasis and suggest that mTOR inhibition can protect podocytes and prevent progressive diabetic nephropathy. PMID:21606591
-
Naringin ameliorates diabetic nephropathy by inhibiting NADPH oxidase 4.
Zhang, Junwei; Yang, Suxia; Li, Huicong; Chen, Fang; Shi, Jun
2017-06-05
Naringin, a naturally flavanone glycoside, has been previously demonstrated to alleviate diabetic kidney disease by inhibiting oxidative stress and inflammatory reaction. However, the underlying mechanism of naringin in diabetic nephropathy (DN) has not been fully elucidated. Here, the beneficial effect of naringin on DN in streptozotocin (STZ)-induced DN rats and high glucose (HG)-induced podocytes and its underlying mechanism were elaborated. The result revealed that naringin alleviated STZ-induced renal dysfunction and injury in DN rats, relieved STZ-induced oxidative stress in vivo and inhibited HG-induced apoptosis and reactive oxygen species level i20n vitro. More importantly, naringin inhibited NOX4 expression at mRNA and protein levels in STZ-induced DN rats and HG-induced podocytes. Loss of function indicated that NADPH oxidases 4 (NOX4) down-regulation suppressed apoptosis and reactive oxygen species level in HG-treated podocytes. Take together, this study demonstrated that naringin ameliorates diabetic nephropathy by inhibiting NOX4, contributing to a better understanding of the progression of DN. Copyright © 2017 Elsevier B.V. All rights reserved.
-
Letter: The clinical course of patients with analgesic nephropathy.
Gault, M. H.
1975-01-01
Thirty-four patients with analgesic nephropathy were followed at intervals of 1 to 3 months with measurements of creatinine clearance and serum concentration of acetylsalicylic acid (ASA) for a total of 105 patient-years. Diagnostic criteria included total consumption of at least 2 kg of phenacetin and 3 kg of ASA, compatible tissue abnormality on biopsy and evidence of papillary necrosis on an intravenous pyelogram. Nephropathy was induced by the same compound analgesic containing ASA, pehnacetin, caffeine and codeine (APC&C) in 30. Phenacetin was removed from this preparation in 1970 and replaced by an approximately equal amount of ASA (ACC). Creatinine clearance remained unchanged or improved in 11 of 15 patients who stopped taking analgesics containing phenacetin or ASA and in 10 of 11 of those who continued to take the ACC preparation. In contrast, renal function deteriorated in seven of eight patients who continued to abuse APC&C analgesics. The results suggest that phenacetin is necessary for the major nephrotoxic effect of this APC&C combination, but that ASA is not absolved of some nephrotoxicity. PMID:1139519
-
Graf, Wolfram; Pauls, Steffen U; Vitecek, Simon
2018-01-09
In this contribution, we describe Isoperla vjosae sp. nov. from Albania. We characterize males, females, and larvae of the new species collected at the Vjosa River using morphological and molecular approaches. Isoperla vjosae sp.nov. is a member of the I. tripartita group, which is widely distributed in the Balkans. This new endemic species is being threatened by a proposed hydroelectric power dam on the Vjosa River impacting the type locality - a large, shifting gravel, low altitude River - an atypical habitat for larvae of the I. tripartita group. For the first time we use molecular tools to delineate Isoperla species from the Balkans.
-
Informal Patient Payments and Bought and Brought Goods in the Western Balkans - A Scoping Review.
Buch Mejsner, Sofie; Eklund Karlsson, Leena
2017-07-03
Informal patient payments for healthcare are common in the Western Balkans, negatively affecting public health and healthcare. To identify literature from the Western Balkans on what is known about informal patient payments and bought and brought goods, to examine their effects on healthcare and to determine what actions can be taken to tackle these payments. After conducting a scoping review that involved searching websites and databases and filtering with eligibility criteria and quality assessment tools, 24 relevant studies were revealed. The data were synthesized using a narrative approach that identified key concepts, types of evidence, and research gaps. The number of studies of informal patient payments increased between 2002 and 2015, but evidence regarding the issues of concern is scattered across various countries. Research has reported incidents of informal patient payments on a wide scale and has described various patterns and characteristics of these payments. Although these payments have typically been small - particularly to providers in common areas of specialized medicine - evidence regarding bought and brought goods remains limited, indicating that such practices are likely even more common, of greater magnitude and perhaps more problematic than informal patient payments. Only scant research has examined the measures that are used to tackle informal patient payments. The evidence indicates that legalizing informal patient payments, introducing performance-based payment systems, strengthening reporting, changing mentalities and involving the media and the European Union (EU) or religious organizations in anti-corruption campaigns are understood as some of the possible remedies that might help reduce informal patient payments. Despite comprehensive evidence regarding informal patient payments, data remain scattered and contradictory, implying that informal patient payments are a complex phenomenon. Additionally, the data on bought and brought goods
-
Prevention of Contrast-Induced Nephropathy (CIN) in Interventional Radiology Practice
Gupta, Rajan K.; Bang, Tami J.
2010-01-01
Contrast-induced nephropathy (CIN) is a widely recognized and clinically significant problem in patients undergoing an increasing number of minimally invasive procedures that require contrast administration. Contrast-induced nephropathy is the third most common cause of hospital-acquired renal failure and has significant prognostic implications on patient outcomes. Interventional practitioners are faced with challenging decisions regarding prophylaxis and patient management. The major risk factor for developing CIN is preexisting renal dysfunction, particularly in association with diabetes. Patients are considered to be at risk when estimated glomerular filtration rate (eGFR) or estimated creatinine clearance (eCCr) is less than 60. The cornerstone of prevention of CIN is appropriate risk stratification, intravenous hydration with normal saline or sodium bicarbonate, appropriate withholding of nephrotoxic medications, use of low or iso-osmolar contrast media, and various intraprocedural methods for iodinated contrast dose reduction. Although N-acetylcysteine administration is popular, it remains unproven. Practitioners must be familiar with prevention strategies and diagnosis of CIN to minimize its clinical impact. PMID:22550376
-
Hydroclimatological Controls of Endemic and Non-endemic Cholera of the 20th Century
NASA Astrophysics Data System (ADS)
Jutla, A. S.; Whitcombe, E.; Colwell, R.
2012-12-01
Cholera remains a major public health threat for the developing countries. Since the causative agent, Vibrio cholerae, is autochthonous to aquatic environment, it is not possible to eradicate the agent of the disease. Hydroclimatology based prediction and prevention strategies can be implemented in disease susceptible regions for reducing incidence rates. However, the precise role of hydrological and climatological processes, which will further aid in development of suitable prediction models, in creating spatial and temporal environmental conditions favorable for disease outbreak has not been adequately quantified. Here, we show distinction between seasonality and occurrence of cholera in epidemic and non-endemic regions. Using historical cholera mortality data, from the late 1800s for 27 locations in the Indian subcontinent, we show that non-endemic regions are generally located close to regional river systems but away from the coasts and are characterized by single sporadic outbreak in a given year. Increase in air temperature during the low river flow season increases evaporation, leading to an optimal salinity and pH required for bacterial growth. Thereafter, monsoonal rainfall, leads to interactions of contaminated river waters via human activity resulting in cholera epidemics. Endemic regions are located close to coasts where cholera outbreak occurs twice (spring and fall) in a year. Spring outbreak is generally associated with intrusion of bacterial seawater to inland whereas the fall peak is correlated with widespread flooding and cross-contamination of water resources via increased precipitation. This may be one of the first studies to hydroclimatologically quantitatively the seasonality of cholera in both endemic and non-endemic regions. Our results prompt the need of region and cause-specific prediction models for cholera, employing appropriate environmental determinants.
-
The influence of ochratoxin A on DNA adduct formation by the carcinogen aristolochic acid in rats.
Stiborová, Marie; Bárta, František; Levová, Kateřina; Hodek, Petr; Frei, Eva; Arlt, Volker M; Schmeiser, Heinz H
2015-11-01
Exposure to the plant nephrotoxin and carcinogen aristolochic acid (AA) leads to the development of AA nephropathy, Balkan endemic nephropathy (BEN) and upper urothelial carcinoma (UUC) in humans. Beside AA, exposure to ochratoxin A (OTA) was linked to BEN. Although OTA was rejected as a factor for BEN/UUC, there is still no information whether the development of AA-induced BEN/UUC is influenced by OTA exposure. Therefore, we studied the influence of OTA on the genotoxicity of AA (AA-DNA adduct formation) in vivo. AA-DNA adducts were formed in liver and kidney of rats treated with AA or AA combined with OTA, but no OTA-related DNA adducts were detectable in rats treated with OTA alone or OTA combined with AA. Compared to rats treated with AA alone, AA-DNA adduct levels were 5.4- and 1.6-fold higher in liver and kidney, respectively, of rats treated with AA combined with OTA. Although AA and OTA induced quinone oxidoreductase (NQO1) activating AA to DNA adducts, their combined treatment did not lead to either higher NQO1 enzyme activity or higher AA-DNA adduct levels in ex vivo incubations. Oxidation of AA I (8-methoxy-6-nitrophenanthro[3,4-d]-1,3-dioxole-5-carboxylic acid) to its detoxification metabolite, 8-hydroxyaristolochic acid, was lower in microsomes from rats treated with AA and OTA, and this was paralleled by lower activities of cytochromes P450 1A1/2 and/or 2C11 in these microsomes. Our results indicate that a decrease in AA detoxification after combined exposure to AA and OTA leads to an increase in AA-DNA adduct formation in liver and kidney of rats.
-
Endemism hotspots are linked to stable climatic refugia.
Harrison, Susan; Noss, Reed
2017-01-01
Centres of endemism have received much attention from evolutionists, biogeographers, ecologists and conservationists. Climatic stability is often cited as a major reason for the occurrences of these geographic concentrations of species which are not found anywhere else. The proposed linkage between endemism and climatic stability raises unanswered questions about the persistence of biodiversity during the present era of rapidly changing climate. The current status of evidence linking geographic centres of endemism to climatic stability over evolutionary time was examined. The following questions were asked. Do macroecological analyses support such an endemism-stability linkage? Do comparative studies find that endemic species display traits reflecting evolution in stable climates? Will centres of endemism in microrefugia or macrorefugia remain relatively stable and capable of supporting high biological diversity into the future? What are the implications of the endemism-stability linkage for conservation? Recent work using the concept of climate change velocity supports the classic idea that centres of endemism occur where past climatic fluctuations have been mild and where mountainous topography or favourable ocean currents contribute to creating refugia. Our knowledge of trait differences between narrow endemics and more widely distributed species remains highly incomplete. Current knowledge suggests that centres of endemism will remain relatively climatically buffered in the future, with the important caveat that absolute levels of climatic change and species losses in these regions may still be large. © The Author 2017. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
-
Giacani, Lorenzo
2014-01-01
SUMMARY The agents of human treponematoses include four closely related members of the genus Treponema: three subspecies of Treponema pallidum plus Treponema carateum. T. pallidum subsp. pallidum causes venereal syphilis, while T. pallidum subsp. pertenue, T. pallidum subsp. endemicum, and T. carateum are the agents of the endemic treponematoses yaws, bejel (or endemic syphilis), and pinta, respectively. All human treponematoses share remarkable similarities in pathogenesis and clinical manifestations, consistent with the high genetic and antigenic relatedness of their etiological agents. Distinctive features have been identified in terms of age of acquisition, most common mode of transmission, and capacity for invasion of the central nervous system and fetus, although the accuracy of these purported differences is debated among investigators and no biological basis for these differences has been identified to date. In 2012, the World Health Organization (WHO) officially set a goal for yaws eradication by 2020. This challenging but potentially feasible endeavor is favored by the adoption of oral azithromycin for mass treatment and the currently focused distribution of yaws and endemic treponematoses and has revived global interest in these fascinating diseases and their causative agents. PMID:24396138
-
Losartan for the nephropathy of sickle cell anemia: A phase-2, multicenter trial.
Quinn, Charles T; Saraf, Santosh L; Gordeuk, Victor R; Fitzhugh, Courtney D; Creary, Susan E; Bodas, Prasad; George, Alex; Raj, Ashok B; Nero, Alecia C; Terrell, Catherine E; McCord, Lisa; Lane, Adam; Ackerman, Hans C; Yang, Yu; Niss, Omar; Taylor, Michael D; Devarajan, Prasad; Malik, Punam
2017-09-01
Nephropathy is a common and progressive complication of sickle cell anemia (SCA). In SCA mice, we found that hyperangiotensinemia in the absence of hypertension underlies nephropathy, and its downregulation by losartan, an angiotensin-II-receptor-1 blocker, reduced albuminuria and progression of nephropathy. Therefore, we performed a phase-2 trial of oral losartan, given for 6 months, to explore whether it reduced albuminuria in children and adults with SCA. Participants were allocated to groups defined by class of baseline urinary albumin-to-creatinine ratio (UACR): no albuminuria (NoA), microalbuminuria (MicroA), and macroalbuminuria (MacroA). The primary endpoint was a ≥25% reduction UACR from baseline. There were 32 evaluable participants (mean age 24 years; NoA = 14, MicroA = 12, MacroA = 6). The primary endpoint was met in 83% of the MacroA group (P < 0.0001) and 58% of the MicroA group (P < 0.0001). Median fold-change in UACR was -0.74 for MacroA and -0.46 for MicroA. In MacroA and MicroA, UACR classification improved in 50% but worsened in 11%. Urine osmolality and estimated glomerular filtration rate (eGFR) did not change significantly. Losartan was discontinued in three participants [leg cramps, N = 1; decline in eGFR >25% (142➝104 mL/minute/1.73 m 2 ), N = 1; rise in serum creatinine >50% (0.2➝0.3 mg/dL), N = 1]. Albuminuria was associated with diastolic dysfunction and impaired functional capacity, although cardiopulmonary status was unchanged after 6 months of losartan therapy. In summary, losartan decreased urinary albumin excretion in most participants with albuminuria. Those with macroalbuminuria had the greatest benefit. This study forms the basis for a phase-3, randomized, placebo-controlled trial of losartan for the nephropathy of SCA. © 2017 Wiley Periodicals, Inc.
-
A case of palpable purpura and nephropathy: Occam's Razor or Hickam's Dictum.
Mandhadi, Ranadeep; Kodumuri, Vamsi; Arora, Rohit; Puneet Singh, Param; Adigopula, Shashi; Chua, Serafin
2013-01-01
Vasculitis causing palpable purpura, nephropathy, and hematologic abnormalities is a well-known entity. However, sometimes, vasculitis may not be the primary cause but is part of a systemic disease. Literature suggests that infections like HIV can induce nephropathy and antineutrophilic cytoplasmic antibody-positive vasculitis, which is different from the well-known entity of "antineutrophilic cytoplasmic antibody-associated vasculitis." We present a 46-year-old female patient with a history of intravenous drug abuse who reported with a rash, swelling, and palpable purpura of the lower extremities. Peripheral smear showed no evidence of disseminated intravascular coagulation or thrombotic thrombocytopenic purpura; metabolic profile showed acute kidney injury. She was found to be HIV- and hepatitis C-positive. Immunologic workup was positive for both MPO and PR3 antineutrophilic cytoplasmic antibodies and negative for cryoglobulins; complement levels were low. Skin biopsy showed leukocytoclastic vasculitis but kidney biopsy was negative for any immunologic involvement; it showed only glomerulosclerosis. Thus, it was thought that nephropathy and vasculitis, in this case, are two distinct pathologic processes, both induced by infection (HIV and/or hepatitis C). The patient responded to low-dose steroid therapy. She was later started on the definitive therapy, the highly active antiretroviral therapy regimen. This case illustrates the fact that low-dose steroids can still be a good alternative in acute situations in patients at risk from immunosuppression.
-
Early detection of acute tubulointerstitial nephritis in the genesis of Mesoamerican nephropathy.
Fischer, Rebecca S B; Vangala, Chandan; Truong, Luan; Mandayam, Sreedhar; Chavarria, Denis; Granera Llanes, Orlando M; Fonseca Laguna, Marcos U; Guerra Baez, Alvaro; Garcia, Felix; García-Trabanino, Ramón; Murray, Kristy O
2018-03-01
Mesoamerican nephropathy is a devastating disease of unknown etiology that affects mostly young agricultural workers in Central America. An understanding of the mechanism of injury and the early disease process is urgently needed and will aid in identification of the underlying cause and direct treatment and prevention efforts. We sought to describe the renal pathology in Mesoamerican nephropathy at its earliest clinical appearance in prospectively identified acute case patients in Nicaragua. We considered those with elevated (or increased at least 0.3 mg/dL or 1.5-fold from baseline) serum creatinine, leukocyturia, and either leukocytosis or neutrophilia for inclusion in this biopsy study. Renal tissue was obtained by ultrasound-guided biopsy for examination by light, immunofluorescence, and electron microscopy. All 11 individuals who underwent renal biopsy showed tubulointerstitial nephritis, with varying degrees of inflammation and chronicity. Interstitial cellular infiltrates (predominantly T lymphocytes and monocytes), mostly in the corticomedullary junction; neutrophilic accumulation in the tubular lumens; largely preserved glomeruli; few mild ischemic changes; and no immune deposits were noted. The acute components of tubulointerstitial nephritis were acute tubular cell injury, interstitial edema, and early fibrosis. Chronic tubulointerstitial nephritis included severe tubular atrophy, thickened tubular basement membrane, and interstitial fibrosis. Thus, renal histopathology in Mesoamerican nephropathy reveals primary interstitial disease with intact glomeruli. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
-
Eriguchi, Masahiro; Lin, Mercury; Yamashita, Michifumi; Zhao, Tuantuan V; Khan, Zakir; Bernstein, Ellen A; Gurley, Susan B; Gonzalez-Villalobos, Romer A; Bernstein, Kenneth E; Giani, Jorge F
2018-04-01
Diabetic nephropathy is a major cause of end-stage renal disease in developed countries. While angiotensin-converting enzyme (ACE) inhibitors are used to treat diabetic nephropathy, how intrarenal ACE contributes to diabetic renal injury is uncertain. Here, two mouse models with different patterns of renal ACE expression were studied to determine the specific contribution of tubular vs. glomerular ACE to early diabetic nephropathy: it-ACE mice, which make endothelial ACE but lack ACE expression by renal tubular epithelium, and ACE 3/9 mice, which lack endothelial ACE and only express renal ACE in tubular epithelial cells. The absence of endothelial ACE normalized the glomerular filtration rate and endothelial injury in diabetic ACE 3/9 mice. However, these mice developed tubular injury and albuminuria and displayed low renal levels of megalin that were similar to those observed in diabetic wild-type mice. In diabetic it-ACE mice, despite hyperfiltration, the absence of renal tubular ACE greatly reduced tubulointerstitial injury and albuminuria and increased renal megalin expression compared with diabetic wild-type and diabetic ACE 3/9 mice. These findings demonstrate that endothelial ACE is a central regulator of the glomerular filtration rate while tubular ACE is a key player in the development of tubular injury and albuminuria. These data suggest that tubular injury, rather than hyperfiltration, is the main cause of microalbuminuria in early diabetic nephropathy.
-
Regional isolation in the Balkan region: an analysis of craniofacial variation.
Ross, Ann H
2004-05-01
Biological variation is investigated among contemporary Croatians, Bosnians, American whites, and other multitemporal Balkan populations (World War II Croatians, Macedonians, and Greeks) via multivariate statistics and distance measures of the craniofacial complex. This study demonstrates that there is considerable variation among groups of European ancestry. Bosnians and Croatians who are thought to be relatively homogenous and historically to originate from the same Slav ancestry show local variations. While environmental plasticity has been used to explain cranial changes among human groups, it does not adequately explain the variation observed between Bosnians and Croatians. It is an oversimplification to exclusively attribute the vast range of variability observed among local as well as geographic populations to environmental adaptations. Copyright 2003 Wiley-Liss, Inc.
-
Segarra, A
2010-01-01
Progress in understanding the pathogenesis of IgA nephropathy has shown that probably there is no a single IgA nephropathy with the same pathogenic mechanism, clinical course and response to therapy. The evidence currently available suggests the existence of at least two possible mechanisms of IgA deposition in the renal mesangium. In a small percentage of patients, mesangial deposition of IgA1 colocalizes with secretory component, indicating that the deposited IgA1 in glomeruli originates completely or partly in the mucose-associated lymphoid tissue. This deposition pattern has been associated with activation of complement by the lectin pathway and has been associated with a worse prognosis, although this last statement needs to be confirmed in long-term studies. The mechanisms responsible for secretory IgA deposition are not known. In the majority of patients with IgA nephropathy secretory component is not detectable in the mesangium. In these cases, the presence of elevated circulating levels of galactose-deficient IgA, produced by bone marrow plasma cells would be a predisposing factor but not sufficient to induce nephropathy. To produce kidney disease, galactose-deficient IgA1 must be deposited in the renal mesangium, and once there, either by interaction with specific receptors (CD71?), by direct activation of complement or by being the target of an IgG autoimmune response anti-IgA, induce activation, proliferation and increased mesangial matrix synthesis and eventually cell injury. In parallel, galactose-deficient IgA, through interaction with the RR Fc alpha/gamma, may activate circulating lymphocytes and monocytes and enhance their response to chemoattractants produced by the mesangial cell, causing, thus, the inflammatory infiltrate to initiate and maintain the interstitial injury. In the next few years, advances recently added to the knowledge of the pathogenesis of nephropathy IgA1 could provide new variables that allow walking in the direction of
-
Cheng, Genyang; Liu, Dongwei; Margetts, Peter; Liu, Limin; Zhao, Zhanzheng; Liu, Zhangsuo; Tang, Lin; Fang, Yudong; Li, Haijian; Guo, Yuanyuan; Chen, Fengmei; Liu, Fengxun
2015-02-01
The current standard treatment for IgA nephropathy relies on steroid and/or immunosuppressive therapy and angiotensin converting enzyme inhibitors (ACEI) or angiotensin receptor blocker (ARB). This study examines the benefits and safety of combining valsartan with clopidogrel and leflunomide as a treatment for progressive IgA nephropathy. Patients with primary IgA nephropathy, confirmed by renal biopsy, were recruited for this study. Patients were separated into four groups (n = 42 each) after 2 months of run-in period of valsartan treatment. All patients were treated with valsartan alone (Group 1) or valsartan and either clopidogrel (Group 2) or leflunomide (Group 3) or both clopidogrel and leflunomide (Group 4). Each group was followed up for their next 24 months for 24 h urinary protein excretion, serum creatinine and estimated glomerular filtration rate (eGFR) to assess the effect of the treatment. Adverse effects were recorded concurrently to evaluate the safety of the treatment. Of all 168 patients, 107 were males and 61 were females, with an average age of 33.8 ± 8.79 years. Baseline characteristics were comparable among the four groups (P > 0.05) prior to the experimental treatment. There was a significant (P < 0.05) decrease in 24 h urinary protein excretion after 4 months of experimental treatment. At the end of the 24 months, groups 3 and 4 showed a respective 62.35% and 69.47% reduction in proteinuria. The serum creatinine was significantly higher (P < 0.05) in group 1 and 2 at the end of the follow-up, and their respective eGFR was significantly lower. The incidence of cardiovascular complication was 11.9% and 9.5% for group 1 and 3, respectively. The treatment with Valsartan combined with Clopidogrel and Leflunomide can reduce the urinary proteins loss and renal function deterioration for IgA nephropathy patients and cause minimal adverse reactions. Our study suggests a new clinical treatment option for IgA nephropathy.
-
Vijay, Soorampally; Hamide, Abdoul; Senthilkumar, Gandhipuram Periyasamy; Mehalingam, Vadivelan
2018-04-12
Renal tubulo-interstitial damage has an important role in the pathogenesis of early diabetic nephropathy. Urinary biomarkers can help in the detection of early nephropathy in type 2 diabetic patients. The aim of this study was to estimate the levels of urinary neutrophil gelatinase associated lipocalin (NGAL) and cystatin-C in type 2 diabetic patients with early diabetic nephropathy & to compare them with diabetic patients without nephropathy and to correlate urinary NGAL and cystatin-C levels with microalbuminuria in them. Cross-sectional comparative study. The study was conducted on 126 patients with type 2 diabetes along with 30 control subjects attending the outpatient care department of a tertiary care teaching hospital. There were 3 study groups-diabetic patients with microalbuminuria, diabetic patients without albuminuria and control subjects who were non-diabetic without any renal disease. Details on duration of diabetes and glycemic status were obtained from the patients. Urine examination was done for subjects in all the groups to look for microalbuminuria along with estimation of NGAL and cystatin-C levels. Samples were stored at -20 °C in the deep freezer. Urinary NGAL and cystatin-C levels were significantly elevated in patients with microalbuminuria (228.18 & 3.23 ng/ml) as compared to those without albuminuria (146.12 & 2.61 ng/ml) and in control subjects (26.56 & 0.30 ng/ml). Urinary NGAL and cystatin-C levels showed a linear correlation with microalbuminuria in diabetic patients. Urinary NGAL and cystatin-C levels were increased in type 2 diabetic patients with early diabetic nephropathy as compared to patients without nephropathy. Urine NGAL and cystatin-C levels also showed a positive correlation with microalbuminuria (urine albumin-creatinine ratio) in patients with type 2 diabetes mellitus. Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.
-
Pini, Alessandro; Grange, Cristina; Veglia, Eleonora; Argenziano, Monica; Cavalli, Roberta; Guasti, Daniele; Calosi, Laura; Ghè, Corrado; Solarino, Roberto; Thurmond, Robin L; Camussi, Giovanni; Chazot, Paul L; Rosa, Arianna Carolina
2018-02-01
Due to the incidence of diabetes and the related morbidity of diabetic nephropathy, identification of new therapeutic strategies represents a priority. In the last few decades new and growing evidence on the possible role of histamine in diabetes has been provided. In particular, the histamine receptor H 4 R is emerging as a new promising pharmacological target for diabetic nephropathy. The aim of this study was to evaluate the efficacy of selective H 4 R antagonism by JNJ39758979 on the prevention of diabetic nephropathy progression in a murine model of diabetes induced by streptozotocin injection. JNJ39758979 (25, 50, 100 mg/kg/day p.o.) was administered for 15 weeks starting from the onset of diabetes. Functional parameters were monitored throughout the experimental period. JNJ39758979 did not significantly affect glycaemic status or body weight. The urine analysis indicated a dose-dependent inhibitory effect of JNJ39758979 on Albumin-Creatinine-Ratio, the Creatinine Clearance, the 24 h urine volume, and pH urine acidification (P < 0.05). The beneficial effects of JNJ39758979 on renal function paralleled comparable effects on renal morphological integrity. These effects were sustained by a significant immune infiltration and fibrosis reduction. Notably, megalin and sodium-hydrogen-exchanger 3 expression levels were preserved. Our data suggest that the H 4 R participates in diabetic nephropathy progression through both a direct effect on tubular reabsorption and an indirect action on renal tissue architecture via inflammatory cell recruitment. Therefore, H 4 R antagonism emerges as a possible new multi-mechanism therapeutic approach to counteract development of diabetic nephropathy development. Copyright © 2018 Elsevier Ltd. All rights reserved.
-
Mihanfar, Aynaz; Rahmati-Yamchi, Mohammad; Mota, Ali; Abediazar, Sima; Pilehvar-Soltanahmadi, Younes; Zarghami, Nosratollah
2018-01-01
Diabetic Nephropathy (DN), a serious and prevalent complication of diabetes, has been rapidly raising worldwide. Vaspin, as an adipokine with anti-diabetic effects, is predominantly released from visceral adipose tissue. Moreover, vaspin has the stimulatory effect on nitric oxide (NO) bioavailability through the activation of NO synthase. The aim of the present study was to investigate the serum levels of vaspin and their correlation with NO metabolite in diabetic patients with normal renal function and renal insufficiency. Volunteers patients with non-nephropathy Type 2 Diabetic Mellitus (T2DM) as control (n=40, age= 56.95±6.11 years) and patients with diabetic nephropathy (DN) (n=40, age=57.85±5.63 years) as case group were enrolled in this study, and serum samples were collected for the measurement of vaspin levels by ELISA technique. Also, serum levels of NO metabolites were calorimetrically assessed. We found that vaspin levels significantly decreased in diabetic patients with nephropathic condition as compared with diabetic patients with normal renal function (p <0.04). In addition, serum levels of NO metabolites were significantly higher in diabetic patients with nephropathy in comparison with non-nephropathic diabetics (p<0.001). When patients with DN were studied, vaspin levels positively correlated with NO metabolites and Homeostasis model assessment of insulin resistance (HOMA-IR) levels. This study showed that low serum vaspin levels may be a risk factor for nephropathy in type II diabetic patients and increased levels of NO may be a defensive mechanism in the DN. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
-
Nephropathy associated with animal, plant, and chemical toxins in the tropics.
Jha, Vivekanand; Chugh, Kirpal S
2003-01-01
Widespread human exposure to a variety of drugs, chemicals, and biologic products and recent awareness of their toxic manifestations has led to the recognition of toxic nephropathy as an important segment of renal disease in the tropical countries. Tropical nephrotoxins are distinctly different from those seen in the rest of the world and are derived from local fauna and flora or plant and chemical sources. The spectrum of exposure varies from country to country and even from community to community, depending on variations in the distribution of local plants and animal species and prevalent social practices. Acute renal failure (ARF), either alone or in association with liver failure, neurologic abnormalities, metabolic acidosis, disseminated intravascular coagulation, or pulmonary infections is the most common form of presentation. Traditional medicines prescribed by witch doctors (traditional healers) constitute a special class of nephrotoxins among several communities in Africa and Asia. The prevalence of nephropathy caused by traditional medicines is directly related to a combination of ignorance, poverty, lack of medical facilities, lax legislation, and widespread belief in indigenous systems of medicine in rural areas. These medicines are a mix of herbs and unknown chemicals administered orally or as enemas. Clustering of cases after exposure to a particular agent suggests the possibility of a toxic insult. Common animal nephrotoxins are venoms of viper snakes, sea snakes, stinging insects, and raw gallbladder and bile of carp and sheep. Botanical nephrotoxins are encountered both in common edible plants (djenkol beans, mushrooms) and medicinal herbs (impila, cat's claw). Mistaken identification of medicinal herbs by untrained workers and even deliberate trials of toxic substitutes derived from plants frequently lead to renal disease, the most commonly reported being the Chinese herbal nephropathy. Nephrotoxicity caused by chemicals can be secondary to
-
IgA nephropathy in systemic lupus erythematosus patients: case report and literature review.
da Silva, Leonardo Sales; Almeida, Bruna Laiza Fontes; de Melo, Ana Karla Guedes; de Brito, Danielle Christine Soares Egypto; Braz, Alessandra Sousa; Freire, Eutília Andrade Medeiros
2016-01-01
Systemic erythematosus lupus (SLE) is a multisystemic autoimmune disease which has nephritis as one of the most striking manifestations. Although it can coexist with other autoimmune diseases, and determine the predisposition to various infectious complications, SLE is rarely described in association with non-lupus nephropathies etiologies. We report the rare association of SLE and primary IgA nephropathy (IgAN), the most frequent primary glomerulopathy in the world population. The patient was diagnosed with SLE due to the occurrence of malar rash, alopecia, pleural effusion, proteinuria, ANA 1: 1280, nuclear fine speckled pattern, and anticardiolipin IgM and 280U/mL. Renal biopsy revealed mesangial hypercellularity with isolated IgA deposits, consistent with primary IgAN. It was treated with antimalarial drug, prednisone and inhibitor of angiotensin converting enzyme, showing good progress. Since they are relatively common diseases, the coexistence of SLE and IgAN may in fact be an uncommon finding for unknown reasons or an underdiagnosed condition. This report focus on the importance of the distinction between the activity of renal disease in SLE and non-SLE nephropathy, especially IgAN, a definition that has important implications on renal prognosis and therapeutic regimens to be adopted in both the short and long terms. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.
-
Hemizygous Fabry disease associated with membranous nephropathy: A rare case report .
Zhou, Wenyan; Ni, Zhaohui; Zhang, Minfang
2018-05-24
Fabry disease may coexist with various glomerular diseases, including IgA nephropathy, focal segmental glomerulosclerosis, etc. In this study, we report a rare case of Fabry disease associated with membranous nephropathy (MN). A 30-year-old man with nephrotic proteinuria, normal renal function, and no other extrarenal manifestations underwent a renal biopsy in February 2017. Light microscopy and immunofluorescence indicated MN (stage 1). Under an electron microscope, there were subepithelial electron-dense deposits and abundant zebra bodies in podocytes. Both the findings of low-activity α-galactosidase A (α-Gal A, GLA) and base deletion in exon 7 of the GLA gene (GLA-E07.1286_*7 del, a newly reported mutation) confirmed that this patient was simultaneously afflicted with Fabry disease. This case report is an important reminder of the role of kidney biopsy, especially electron microscopy, as an indicator of Fabry disease and its rare coexistence with MN. .
-
Decreased TIM-3 mRNA expression in peripheral blood mononuclear cells from nephropathy patients.
Cai, X Z; Liu, N; Qiao, Y; Du, S Y; Chen, Y; Chen, D; Yu, S; Jiang, Y
2015-06-12
Increasing evidence shows that TIM-1 and TIM-3 in-fluence chronic autoimmune diseases, and their expression levels in immune cells from nephritic patients are still unknown. Real-time transcription-polymerase chain reaction analysis was used to deter-mine expression levels of TIM-1 and TIM-3 mRNA in peripheral blood mononuclear cells (PBMCs) from 36 patients with minimal change glo-merulopathy (MCG), 65 patients with lupus nephritis (LN), 78 patients with IgA nephropathy (IgAN), 55 patients with membranous nephropa-thy (MN), 22 patients with crescentic glomerulonephritis (CGN), 26 patients with anaphylactoid purpura nephritis (APN), and 63 healthy controls. TIM-3 mRNA expression significantly decreased in PBMCs from nephritic patients (LN, P < 0.0001; MCG, P < 0.0001; MN, P = 0.0031; CGN, P = 0.0464; IgAN, P = 0.0002; APN, P = 0.0392) com-pared with healthy controls. In contrast, there was no significant differ-ence in TIM-1 mRNA expression between the patients and the healthy controls. Our results suggest that insufficient expression of TIM-3 mRNA may be involved in the pathogenesis of nephropathy.
-
Huang, Shan-Shan; Ding, Da-Fa; Chen, Sheng; Dong, Cheng-Long; Ye, Xiao-Long; Yuan, Yang-Gang; Feng, Ya-Min; You, Na; Xu, Jia-Rong; Miao, Heng; You, Qiang; Lu, Xiang; Lu, Yi-Bing
2017-01-01
Podocyte apoptosis coincides with albuminuria onset and precedes podocytopenia in diabetic nephropathy. However, there is a lack of effective therapeutic drugs to protect podocytes from apoptosis. Here, we demonstrated that resveratrol relieved a series of indicators of diabetic nephropathy and attenuated apoptosis of podocytes in db/db diabetic model mice. In addition, resveratrol induced autophagy in both db/db mice and human podocytes. Furthermore, inhibition of autophagy by 3-methyladenine (3-MA) and autophagy gene 5 (Atg5) short hairpin RNA (shRNA) reversed the protective effects of resveratrol on podocytes. Finally, we found that resveratrol might regulate autophagy and apoptosis in db/db mice and podocytes through the suppression of microRNA-383-5p (miR-383-5p). Together, our results indicate that resveratrol effectively attenuates high glucose-induced apoptosis via the activation of autophagy in db/db mice and podocytes, which involves miR-383-5p. Thus, this study reveals a new possible strategy to treat diabetic nephropathy. PMID:28374806
-
Olatunji, Opeyemi Joshua; Chen, Hongxia; Zhou, Yifeng
2018-06-01
Diabetic nephropathy is one of the most serious and most frequently encountered diabetic complication, accounting for the highest cause of end-stage renal disease. This present study was aimed at exploring the protective/attenuative effect of Lycium chinense leaf extract (MELC) on streptozotocin induced diabetic nephropathy in experimental Sprague Dawley rats. The oral administration of diabetic rats with MELC markedly ameliorated renal dysfunction as observed in the significant reduction in the serum levels of creatinine, blood urea nitrogen (BUN), albumin and TGF-β1 as compared to the untreated diabetic control rats. In addition, the elevated levels of renal oxidative stress markers and pro-inflammatory parameters (GSH, SOD, CAT, MDA, TNF-α, IL-6 and IL-1β) were significantly reduced in MELC treated diabetic rats. The results obtained in this study suggests that L. chinense leaf might have the potential as possible pharmacological agent against diabetic nephropathy by suppressing renal oxidative stress and inflammation. Copyright © 2018. Published by Elsevier Masson SAS.
-
Cao, Aili; Wang, Li; Chen, Xia; Guo, Hengjiang; Chu, Shuang; Zhang, Xuemei; Peng, Wen
2016-08-01
Oxidative stress has a great role in diabetes and diabetes induced organ damage. Endoplasmic reticulum (ER) stress is involved in the onset of diabetic nephropathy. We hypothesize that ER stress inhibition could protect against kidney injury through anti-oxidative effects. To test whether block ER stress could attenuate oxidative stress and improve diabetic nephropathy in vivo and in vitro, the effect of ursodeoxycholic acid (UDCA), an ER stress inhibitor, on spontaneous diabetic nephropathy db/db mice, ER stress inducer or high glucose-triggered podocytes were studied. Mice were assigned to 3 groups (n=6 per group): control group (treated with vehicle), db/db group (treated with vehicle), and UDCA group (db/db mice treated with 40 mg/kg/d UDCA). After 8 weeks treatment, mice were sacrificed. Blood and kidneys were collected for the assessment of albumin/creatinine ratio, blood urea nitrogen (BUN), serum creatinine (SCr), insulin, total cholesterol, triglyceride, low density lipoprotein cholesterol (LDL-C), oxidized LDL-C, high density lipoprotein cholesterol (HDL-C), non-esterified fatty acid (NEFA), superoxide dismutase (SOD), catalase (CAT), methane dicarboxylic aldehyde (MDA), the expressions of SOD isoforms and glutathione peroxidase 1, as well as histopathological examination. In addition, generation of reactive oxygen species (ROS) was detected by 2'7'-dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescence. The results showed that UDCA alleviated renal ER stress-evoked cell death, oxidative stress, renal dysfunction, ROS production, upregulated the expression of Bcl-2 and suppressed Bax in vivo and in vitro. Hence, inhibition ER stress diminishes oxidative stress and exerts renoprotective effects.
-
Aberrant DNA methylation patterns in diabetic nephropathy
2014-01-01
Background The aim of this study was to evaluate whether global levels of DNA methylation status were associated with albuminuria and progression of diabetic nephropathy in a case-control study of 123 patients with type 2 diabetes- 53 patients with albuminuria and 70 patients without albuminuria. Methods The 5-methyl cytosine content was assessed by reverse phase high pressure liquid chromatography (RP-HPLC) of peripheral blood mononuclear cells to determine individual global DNA methylation status in two groups. Results Global DNA methylation levels were significantly higher in patients with albuminuria compared with those in normal range of albuminuria (p = 0.01). There were significant differences in global levels of DNA methylation in relation to albuminuria (p = 0.028) and an interesting pattern of increasing global levels of DNA methylation in terms of albuminuria severity. In patients with micro- and macro albuminuria, we found no significant correlations between global DNA methylation levels and duration of diabetes (p > 0.05). In both sub groups, there were not significant differences between global DNA methylation levels with good and poor glycaemic control (p > 0.05). In addition, in patients with albuminuria, no differences in DNA methylation levels were observed between patients with and without other risk factors including age, gender, hypertension, dyslipidaemia and obesity. Conclusions These data may be helpful in further studies to develop novel biomarkers and new strategies for clinical care of patients at risk of diabetic nephropathy. PMID:25028646
-
Gao, Haoxue; Yu, Xiaoyi; Sun, Runbin; Yang, Na; He, Jun; Tao, Mingxue; Gu, Huilin; Yan, Caixia; Aa, Jiye; Wang, Guangji
2018-03-01
The early diagnosis of diabetic nephropathy (DN) is rather challenging. Our previous study suggested that citric acid is a potential marker for the early diagnosis of diabetic nephropathy in db/db mice. For the first time, in this study, a surrogate analyte of 13 C 6 -citric acid was employed to generate calibration curves for the quantitative measurement of the endogenous citric acid in the sera of db/db mice and diabetic nephropathy patients by GC/MS after the analytes were extracted, methoximated and trimethylsilylated. The constant response factor of 13 C 6 -citric acid versus citric acid over the linear range indicated the identical ionization efficiency of these two compounds. The full validation assessments suggested that the method is sensitive, specific, reliable, reproducible and has acceptable parameters. Statistical analysis revealed cut-off citric acid concentrations of 29.24 μg/mL with a 95% confidence interval between 32.75 and 39.16 μg/mL in the diabetic nephropathy patients and 16.74 and 22.57 μg/mL in the normal controls. The areas under the receiver operating characteristic curves indicated accuracies of over 90% for the diagnoses of early diabetic nephropathy in both humans and db/db mice, which suggests that the serum citric acid level is potentially a biomarker that could assist in the diagnosis of diabetic nephropathy. Copyright © 2018 Elsevier B.V. All rights reserved.
-
Nitric oxide system and diabetic nephropathy
2014-01-01
About 30% of patients with type 2 diabetes mellitus develop clinically overt nephropathy. Hyperglycemia is necessary, but not sufficient, to cause the renal damage that leads to kidney failure. Diabetic nephropathy (DN) is a multifactorial disorder that results from interaction between environmental and genetic factors. In the present article we will review the role of the nitric oxide synthase (NOS) in the pathogenesis of DN. Nitric oxide (NO) is a short-lived gaseous lipophilic molecule produced in almost all tissues, and it has three distinct genes that encode three NOS isoforms: neuronal (nNOS), inducible (iNOS) and endothelial (eNOS). The correct function of the endothelium depends on NO, participating in hemostasis control, vascular tone regulation, proliferation of vascular smooth muscle cells and blood pressure homeostasis, among other features. In the kidney, NO plays many different roles, including control of renal and glomerular hemodynamics. The net effect of NO in the kidney is to promote natriuresis and diuresis, along with renal adaptation to dietary salt intake. The eNOS gene has been considered a potential candidate gene for DN susceptibility. Three polymorphisms have been extensively researched: G894T missense mutation (rs1799983), a 27-bp repeat in intron 4, and the T786C single nucleotide polymorphism (SNP) in the promoter (rs2070744). However, the potential link between eNOS gene variants and the induction and progression of DN yielded contradictory results in the literature. In conclusion, NOS seems to be involve in the development and progression of DN. Despite the discrepant results of many studies, the eNOS gene is also a good candidate gene for DN. PMID:24520999
-
ERIC Educational Resources Information Center
Pantic, Natasa; Wubbels, Theo; Mainhard, Tim
2011-01-01
Orientation of teacher preparation toward the development of competence has recently been suggested as a worthwhile direction of change in teacher education in the Western Balkan countries. In this study, 2,354 teachers, teacher educators, and student teachers from Bosnia and Herzegovina, Croatia, Macedonia, Montenegro, and Serbia responded to a…
-
SGLT2 Protein Expression Is Increased in Human Diabetic Nephropathy
Wang, Xiaoxin X.; Levi, Jonathan; Luo, Yuhuan; Myakala, Komuraiah; Herman-Edelstein, Michal; Qiu, Liru; Wang, Dong; Peng, Yingqiong; Grenz, Almut; Lucia, Scott; Dobrinskikh, Evgenia; D'Agati, Vivette D.; Koepsell, Hermann; Kopp, Jeffrey B.; Rosenberg, Avi Z.; Levi, Moshe
2017-01-01
There is very limited human renal sodium gradient-dependent glucose transporter protein (SGLT2) mRNA and protein expression data reported in the literature. The first aim of this study was to determine SGLT2 mRNA and protein levels in human and animal models of diabetic nephropathy. We have found that the expression of SGLT2 mRNA and protein is increased in renal biopsies from human subjects with diabetic nephropathy. This is in contrast to db-db mice that had no changes in renal SGLT2 protein expression. Furthermore, the effect of SGLT2 inhibition on renal lipid content and inflammation is not known. The second aim of this study was to determine the potential mechanisms of beneficial effects of SGLT2 inhibition in the progression of diabetic renal disease. We treated db/db mice with a selective SGLT2 inhibitor JNJ 39933673. We found that SGLT2 inhibition caused marked decreases in systolic blood pressure, kidney weight/body weight ratio, urinary albumin, and urinary thiobarbituric acid-reacting substances. SGLT2 inhibition prevented renal lipid accumulation via inhibition of carbohydrate-responsive element-binding protein-β, pyruvate kinase L, SCD-1, and DGAT1, key transcriptional factors and enzymes that mediate fatty acid and triglyceride synthesis. SGLT2 inhibition also prevented inflammation via inhibition of CD68 macrophage accumulation and expression of p65, TLR4, MCP-1, and osteopontin. These effects were associated with reduced mesangial expansion, accumulation of the extracellular matrix proteins fibronectin and type IV collagen, and loss of podocyte markers WT1 and synaptopodin, as determined by immunofluorescence microscopy. In summary, our study showed that SGLT2 inhibition modulates renal lipid metabolism and inflammation and prevents the development of nephropathy in db/db mice. PMID:28196866
-
Surina, Boštjan; Schneeweiss, Gerald M; Glasnović, Peter; Schönswetter, Peter
2014-06-01
Due to strong spatial heterogeneity and limited Pleistocene glaciation, the Balkan Peninsula is a major European biodiversity hot spot. Surprisingly little, however, is known about patterns and processes of intraspecific diversification of its biota in general and of high-altitude species in particular. A well-suited system to test hypotheses with respect to various isolating factors acting at different geographic scales and to explore full-range phylogeographic patterns on the Balkan Peninsula is Edraianthus graminifolius (Campanulaceae), distributed in the western Balkan mountain systems, the southwestern Carpathians and the Apennine Peninsula. To this end, we used a dense population sampling and employed amplified fragment length polymorphism (AFLP) markers and plastid DNA sequences supplemented by ecological niche modelling. The strongest splits were inferred to separate southern and northern Balkan populations from the central ones, from where range extension occurred to the Carpathians and, in more recent times, once or twice to the Apennine Peninsula. The three genetic groups in the western Balkan Peninsula were remarkably congruent among molecular markers, suggesting that the barriers to gene flow acted over long time periods facilitating allopatric differentiation. Each main group of Balkan populations contained genetically and geographically distinct subgroups, which likely are the result of local refugia during warmer periods. Evidently, the topographically highly complex and during the Last Glacial Maximum only locally glaciated Balkan Peninsula is a hot spot of species richness and endemism as well as a sanctuary of intraspecific genetic diversity, even if the underlying causes remain insufficiently understood. © 2014 John Wiley & Sons Ltd.
-
The Little Ice Age and its Spatial Variability across the Balkans
NASA Astrophysics Data System (ADS)
Kulkarni, C.; Peteet, D. M.; Boger, R. A.
2015-12-01
Using biological proxies (pollen, spores, and charcoal), geochemical signals through X-ray fluorescence, and AMS 14C based chronology, we present a correlation between two new high resolution Little Ice Age (LIA) records from the Central Balkans that are part of one of the least studied regions of Europe. The sediments extracted from a western sinkhole and central Serbian oxbow lake are analyzed at 8-10-cm intervals to capture the nature and magnitude of the LIA at a resolution of 20 years. During the 15th-19th CE, indigenous tree (e.g. Quercus, Acer, Pinus) and herbaceous (e.g. Poaceae, Chenopodiaceae, Artemisia) pollen from these records demonstrate fluctuations in woodland-grassland dynamics. While tree populations from Central Serbia remain comparatively stable (40-60%), the trees of western Serbia vacillate drastically between 15% and 50%. Similarly, central Serbian grasses show variations of ~18-36% whereas the western Serbian grass populations exhibit abrupt oscillations between high (55%) and low (19%) percentages. As a proxy for surface erosion and clastic input into the lakes, the 1-cm resolution potassium and titanium counts are in strong agreement with varying herbaceous taxa. These variations in ecological signals across the cores can account for local factors including altitude, terrain exposure, soils etc., however, the dynamic human component of the landscape is evident through crop pollen (e.g. Cerealia, Juglans) and microscopic charcoal highlighting the dominant role of people in ecological changes. Although the two sites show certain differences in charcoal concentration, extremely high charcoal indicates accelerated land clearance between the 15th and 17th CE. Until the beginning of 18th CE, the cultivars (e.g. Secale, Triticum) occur with very low percentages and then peak to suggest improved agriculture in the region. In the post-LIA era, the 20th CE exhibits increased arboreal percentages and declining grasslands in both the two Central
-
2013-01-01
Background Malaria rapid diagnostic tests (RDTs) are a useful tool in endemic malaria countries, where light microscopy is not feasible. In non-endemic countries they can be used as complementary tests to provide timely results in case of microscopy inexperience. This study aims to compare the new VIKIA Malaria Ag Pf/Pan™ RDT with PCR-corrected microscopy results and the commonly used CareStart™ RDT to diagnose falciparum and non-falciparum malaria in the endemic setting of Bamako, Mali and the non-endemic setting of Lyon, France. Methods Blood samples were collected during a 12-months and six-months period in 2011 from patients suspected to have malaria in Lyon and Bamako respectively. The samples were examined by light microscopy, the VIKIA Malaria Ag Pf/Pan™ test and in Bamako additionally with the CareStart™ RDT. Discordant results were corrected by real-time PCR. Sensitivity, specificity, positive predictive value and negative predictive value were used to evaluate test performance. Results Samples of 877 patients from both sites were included. The VIKIA Malaria Ag Pf/Pan™ had a sensitivity of 98% and 96% for Plasmodium falciparum in Lyon and Bamako, respectively, performing similar to PCR-corrected microscopy. Conclusions The VIKIA Malaria Ag Pf/Pan™ performs similar to PCR-corrected microscopy for the detection of P. falciparum, making it a valuable tool in malaria endemic and non-endemic regions. PMID:23742633
-
Eibach, Daniel; Traore, Boubacar; Bouchrik, Mourad; Coulibaly, Boubacar; Coulibaly, Nianégué; Siby, Fanta; Bonnot, Guillaume; Bienvenu, Anne-Lise; Picot, Stéphane
2013-06-06
Malaria rapid diagnostic tests (RDTs) are a useful tool in endemic malaria countries, where light microscopy is not feasible. In non-endemic countries they can be used as complementary tests to provide timely results in case of microscopy inexperience. This study aims to compare the new VIKIA Malaria Ag Pf/Pan™ RDT with PCR-corrected microscopy results and the commonly used CareStart™ RDT to diagnose falciparum and non-falciparum malaria in the endemic setting of Bamako, Mali and the non-endemic setting of Lyon, France. Blood samples were collected during a 12-months and six-months period in 2011 from patients suspected to have malaria in Lyon and Bamako respectively. The samples were examined by light microscopy, the VIKIA Malaria Ag Pf/Pan™ test and in Bamako additionally with the CareStart™ RDT. Discordant results were corrected by real-time PCR. Sensitivity, specificity, positive predictive value and negative predictive value were used to evaluate test performance. Samples of 877 patients from both sites were included. The VIKIA Malaria Ag Pf/Pan™ had a sensitivity of 98% and 96% for Plasmodium falciparum in Lyon and Bamako, respectively, performing similar to PCR-corrected microscopy. The VIKIA Malaria Ag Pf/Pan™ performs similar to PCR-corrected microscopy for the detection of P. falciparum, making it a valuable tool in malaria endemic and non-endemic regions.
-
The role of oxidative stress in streptozotocin-induced diabetic nephropathy in rats.
Fernandes, Sheila Marques; Cordeiro, Priscilla Mendes; Watanabe, Mirian; Fonseca, Cassiane Dezoti da; Vattimo, Maria de Fatima Fernandes
2016-10-01
The objective of this study was to evaluate the role of oxidative stress in an experimental model of streptozotocin-induced diabetic nephropathy in rats. Wistar, adult, male rats were used in the study. Animals were divided in the following groups: Citrate (control, citrate buffer 0.01M, pH 4.2 was administrated intravenously - i.v - in the caudal vein), Uninephrectomy+Citrate (left uninephrectomy-20 days before the study), DM (streptozotocin, 65 mg/kg, i.v, on the 20th day of the study), Uninephrectomy+DM. Physiological parameters (water and food intake, body weight, blood glucose, kidney weight, and relative kidney weight); renal function (creatinine clearance), urine albumin (immunodiffusion method); oxidative metabolites (urinary peroxides, thiobarbituric acid reactive substances, and thiols in renal tissue), and kidney histology were evaluated. Polyphagia, polydipsia, hyperglycemia, and reduced body weight were observed in diabetic rats. Renal function was reduced in diabetic groups (creatinine clearance, p < 0.05). Uninephrectomy potentiated urine albumin and increased kidney weight and relative kidney weight in diabetic animals (p < 0.05). Urinary peroxides and thiobarbituric acid reactive substances were increased, and the reduction in thiol levels demonstrated endogenous substrate consumption in diabetic groups (p < 0.05). The histological analysis revealed moderate lesions of diabetic nephropathy. This study confirms lipid peroxidation and intense consumption of the antioxidant defense system in diabetic rats. The association of hyperglycemia and uninephrectomy resulted in additional renal injury, demonstrating that the model is adequate for the study of diabetic nephropathy.
-
DNA aptamer raised against AGEs blocks the progression of experimental diabetic nephropathy.
Kaida, Yusuke; Fukami, Kei; Matsui, Takanori; Higashimoto, Yuichiro; Nishino, Yuri; Obara, Nana; Nakayama, Yosuke; Ando, Ryotaro; Toyonaga, Maki; Ueda, Seiji; Takeuchi, Masayoshi; Inoue, Hiroyoshi; Okuda, Seiya; Yamagishi, Sho-ichi
2013-09-01
Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in diabetic nephropathy. We screened DNA aptamer directed against AGEs (AGEs-aptamer) in vitro and examined its effects on renal injury in KKAy/Ta mice, an animal model of type 2 diabetes. Eight-week-old male KKAy/Ta or C57BL/6J mice received continuous intraperitoneal infusion of AGEs- or control-aptamer for 8 weeks. AGEs-aptamer was detected and its level was increased in the kidney for at least 7 days. The elimination half-lives of AGEs-aptamer in the kidney were about 7 days. Compared with those in C57BL/6J mice, glomerular AGEs levels were significantly increased in KKAy/Ta mice, which were blocked by AGEs-aptamer. Urinary albumin and 8-hydroxy-2'-deoxy-guanosine levels were increased, and glomerular hypertrophy and enhanced extracellular matrix accumulation were observed in KKAy/Ta mice, all of which were prevented by AGEs-aptamer. Moreover, AGEs-aptamer significantly reduced gene expression of RAGE, monocyte chemoattractant protein-1, connective tissue growth factor, and type IV collagen both in the kidney of KKAy/Ta mice and in AGE-exposed human cultured mesangial cells. Our present data suggest that continuous administration of AGEs-aptamer could protect against experimental diabetic nephropathy by blocking the AGEs-RAGE axis and may be a feasible and promising therapeutic strategy for the treatment of diabetic nephropathy.
-
DNA Aptamer Raised Against AGEs Blocks the Progression of Experimental Diabetic Nephropathy
Kaida, Yusuke; Fukami, Kei; Matsui, Takanori; Higashimoto, Yuichiro; Nishino, Yuri; Obara, Nana; Nakayama, Yosuke; Ando, Ryotaro; Toyonaga, Maki; Ueda, Seiji; Takeuchi, Masayoshi; Inoue, Hiroyoshi; Okuda, Seiya
2013-01-01
Advanced glycation end products (AGEs) and their receptor (RAGE) play a role in diabetic nephropathy. We screened DNA aptamer directed against AGEs (AGEs-aptamer) in vitro and examined its effects on renal injury in KKAy/Ta mice, an animal model of type 2 diabetes. Eight-week-old male KKAy/Ta or C57BL/6J mice received continuous intraperitoneal infusion of AGEs- or control-aptamer for 8 weeks. AGEs-aptamer was detected and its level was increased in the kidney for at least 7 days. The elimination half-lives of AGEs-aptamer in the kidney were about 7 days. Compared with those in C57BL/6J mice, glomerular AGEs levels were significantly increased in KKAy/Ta mice, which were blocked by AGEs-aptamer. Urinary albumin and 8-hydroxy-2′-deoxy-guanosine levels were increased, and glomerular hypertrophy and enhanced extracellular matrix accumulation were observed in KKAy/Ta mice, all of which were prevented by AGEs-aptamer. Moreover, AGEs-aptamer significantly reduced gene expression of RAGE, monocyte chemoattractant protein-1, connective tissue growth factor, and type IV collagen both in the kidney of KKAy/Ta mice and in AGE-exposed human cultured mesangial cells. Our present data suggest that continuous administration of AGEs-aptamer could protect against experimental diabetic nephropathy by blocking the AGEs-RAGE axis and may be a feasible and promising therapeutic strategy for the treatment of diabetic nephropathy. PMID:23630304
-
Alterations of urinary metabolite profile in model diabetic nephropathy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stec, Donald F.; Wang, Suwan; Stothers, Cody
2015-01-09
Highlights: • {sup 1}H NMR spectroscopy was employed to study urinary metabolite profile in diabetic mouse models. • Mouse urinary metabolome showed major changes that are also found in human diabetic nephropathy. • These models can be new tools to study urinary biomarkers that are relevant to human disease. - Abstract: Countering the diabetes pandemic and consequent complications, such as nephropathy, will require better understanding of disease mechanisms and development of new diagnostic methods. Animal models can be versatile tools in studies of diabetic renal disease when model pathology is relevant to human diabetic nephropathy (DN). Diabetic models using endothelialmore » nitric oxide synthase (eNOS) knock-out mice develop major renal lesions characteristic of human disease. However, it is unknown whether they can also reproduce changes in urinary metabolites found in human DN. We employed Type 1 and Type 2 diabetic mouse models of DN, i.e. STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db, with the goal of determining changes in urinary metabolite profile using proton nuclear magnetic resonance (NMR). Six urinary metabolites with significantly lower levels in diabetic compared to control mice have been identified. Specifically, major changes were found in metabolites from tricarboxylic acid (TCA) cycle and aromatic amino acid catabolism including 3-indoxyl sulfate, cis-aconitate, 2-oxoisocaproate, N-phenyl-acetylglycine, 4-hydroxyphenyl acetate, and hippurate. Levels of 4-hydroxyphenyl acetic acid and hippuric acid showed the strongest reverse correlation to albumin-to-creatinine ratio (ACR), which is an indicator of renal damage. Importantly, similar changes in urinary hydroxyphenyl acetate and hippurate were previously reported in human renal disease. We demonstrated that STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db mouse models can recapitulate changes in urinary metabolome found in human DN and therefore can
-
Bradshaw, Peter L.; Colville, Jonathan F.; Linder, H. Peter
2015-01-01
We used a very large dataset (>40% of all species) from the endemic-rich Cape Floristic Region (CFR) to explore the impact of different weighting techniques, coefficients to calculate similarity among the cells, and clustering approaches on biogeographical regionalisation. The results were used to revise the biogeographical subdivision of the CFR. We show that weighted data (down-weighting widespread species), similarity calculated using Kulczinsky’s second measure, and clustering using UPGMA resulted in the optimal classification. This maximized the number of endemic species, the number of centres recognized, and operational geographic units assigned to centres of endemism (CoEs). We developed a dendrogram branch order cut-off (BOC) method to locate the optimal cut-off points on the dendrogram to define candidate clusters. Kulczinsky’s second measure dendrograms were combined using consensus, identifying areas of conflict which could be due to biotic element overlap or transitional areas. Post-clustering GIS manipulation substantially enhanced the endemic composition and geographic size of candidate CoEs. Although there was broad spatial congruence with previous phytogeographic studies, our techniques allowed for the recovery of additional phytogeographic detail not previously described for the CFR. PMID:26147438
-
ERIC Educational Resources Information Center
Jelavich, Barbara
Designed as an introductory history, this book covers developments in the Balkan Peninsula from the 17th through the 19th centuries. Emphasis is placed on the process by which separate nationalities broke away from imperial rule, established independent states, and embarked on economic and social modernization. To establish perspective on the role…
-
Complement factor H-related proteins in IgA nephropathy-sometimes a gentle nudge does the trick.
Thurman, Joshua M; Laskowski, Jennifer
2017-10-01
Complement activation probably contributes to glomerular inflammation and damage in IgA nephropathy. In this issue, 2 groups report that levels of factor H-related protein 1 are elevated in patients with IgA nephropathy and correlate with disease progression. These studies provide new evidence that the complement cascade is important to the pathogenesis of this disease. These results also suggest that factor H-related protein 1 levels may be useful for identifying those patients at high risk of disease progression. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
-
Endemism hotspots are linked to stable climatic refugia
Noss, Reed
2017-01-01
Background Centres of endemism have received much attention from evolutionists, biogeographers, ecologists and conservationists. Climatic stability is often cited as a major reason for the occurrences of these geographic concentrations of species which are not found anywhere else. The proposed linkage between endemism and climatic stability raises unanswered questions about the persistence of biodiversity during the present era of rapidly changing climate. Key Questions The current status of evidence linking geographic centres of endemism to climatic stability over evolutionary time was examined. The following questions were asked. Do macroecological analyses support such an endemism–stability linkage? Do comparative studies find that endemic species display traits reflecting evolution in stable climates? Will centres of endemism in microrefugia or macrorefugia remain relatively stable and capable of supporting high biological diversity into the future? What are the implications of the endemism–stability linkage for conservation? Conclusions Recent work using the concept of climate change velocity supports the classic idea that centres of endemism occur where past climatic fluctuations have been mild and where mountainous topography or favourable ocean currents contribute to creating refugia. Our knowledge of trait differences between narrow endemics and more widely distributed species remains highly incomplete. Current knowledge suggests that centres of endemism will remain relatively climatically buffered in the future, with the important caveat that absolute levels of climatic change and species losses in these regions may still be large. PMID:28064195
-
2001-10-01
property , forcible eviction of entire villages, widespread rape and torture, and massacres of innocent women, children, and the elderly BALKANS-1 6...and Italy also have unresolved issues dating from World War II over property and ethnic minority rights. Serbia and Montenegro also dispute Croatia’s...positions (Jayne, 1910). Dating from the Ottoman occupation, Moslem nobles and landlords held all land other than gardens and residential properties
-
Huang, Chunling; Zhang, Yuan; Kelly, Darren J.; Tan, Christina Y. R.; Gill, Anthony; Cheng, Delfine; Braet, Filip; Park, Jin-Sung; Sue, Carolyn M.; Pollock, Carol A.; Chen, Xin-Ming
2016-01-01
Hyperglycemia upregulates thioredoxin interacting protein (TXNIP) expression, which in turn induces ROS production, inflammatory and fibrotic responses in the diabetic kidney. Dysregulation of autophagy contributes to the development of diabetic nephropathy. However, the interaction of TXNIP with autophagy/mitophagy in diabetic nephropathy is unknown. In this study, streptozotocin-induced diabetic rats were given TXNIP DNAzyme or scrambled DNAzyme for 12 weeks respectively. Fibrotic markers, mitochondrial function and mitochondrial reactive oxygen species (mtROS) were assessed in kidneys. Tubular autophagy and mitophagy were determined in kidneys from both human and rats with diabetic nephropathy. TXNIP and autophagic signaling molecules were examined. TXNIP DNAzyme dramatically attenuated extracellular matrix deposition in the diabetic kidneys compared to the control DNAzyme. Accumulation of autophagosomes and reduced autophagic clearance were shown in tubular cells of human diabetic compared to non-diabetic kidneys, which was reversed by TXNIP DNAzyme. High glucose induced mitochondrial dysfunction and mtROS production, and inhibited mitophagy in proximal tubular cells, which was reversed by TXNIP siRNA. TXNIP inhibition suppressed diabetes-induced BNIP3 expression and activation of the mTOR signaling pathway. Collectively, hyperglycemia-induced TXNIP contributes to the dysregulation of tubular autophagy and mitophagy in diabetic nephropathy through activation of the mTOR signaling pathway. PMID:27381856
-
Correlation between Serum Uric Acid Level and Microalbuminuria in Type-2 Diabetic Nephropathy
Latif, Hina; Iqbal, Adil; Rathore, Rabia; Butt, Nasir Farooq
2017-01-01
Objective: To measure the correlation between microalbuminuria and serum uric acid level in Type-2 diabetic nephropathy. Methods: This cross-sectional study was done in department of Medicine, Mayo hospital Lahore from August 2014 to February 2015. A total of 200 patients with Type-2 diabetic nephropathy were enrolled in the study. Demographic data and contact details were obtained. Serum Uric acid and microalbuminuria by albumin to creatinine ratio (ACR) in random urine sample was measured at the time of inclusion of patients. All the information was collected through a pre-defined proforma. Pearson correlation coefficient and t-test were used to assess correlation and significance respectively. Results: Out of 200 cases, 29%(n=58) were between 16-40 years of age while 71%(n=142) were between 41-65 years of age, Mean ± SD was calculated as 48.1±10.26 years, 48.5%(n=97) were male and 51.5%(n=103) were females, Mean serum uric acid level was calculated as 6.99±1.01 mg/dL while microalbuminuria was calculated as 5.63±1.08 mg/mmol, r value was 0.0838 which is a positive correlation. Conclusion: The results of our study concluded that level of serum uric acid and microalbuminuria are significantly correlated to nephropathy in patients having Type-2 diabetes mellitus. PMID:29492061
-
Updated Global Burden of Cholera in Endemic Countries
Ali, Mohammad; Nelson, Allyson R.; Lopez, Anna Lena; Sack, David A.
2015-01-01
Background The global burden of cholera is largely unknown because the majority of cases are not reported. The low reporting can be attributed to limited capacity of epidemiological surveillance and laboratories, as well as social, political, and economic disincentives for reporting. We previously estimated 2.8 million cases and 91,000 deaths annually due to cholera in 51 endemic countries. A major limitation in our previous estimate was that the endemic and non-endemic countries were defined based on the countries’ reported cholera cases. We overcame the limitation with the use of a spatial modelling technique in defining endemic countries, and accordingly updated the estimates of the global burden of cholera. Methods/Principal Findings Countries were classified as cholera endemic, cholera non-endemic, or cholera-free based on whether a spatial regression model predicted an incidence rate over a certain threshold in at least three of five years (2008-2012). The at-risk populations were calculated for each country based on the percent of the country without sustainable access to improved sanitation facilities. Incidence rates from population-based published studies were used to calculate the estimated annual number of cases in endemic countries. The number of annual cholera deaths was calculated using inverse variance-weighted average case-fatality rate (CFRs) from literature-based CFR estimates. We found that approximately 1.3 billion people are at risk for cholera in endemic countries. An estimated 2.86 million cholera cases (uncertainty range: 1.3m-4.0m) occur annually in endemic countries. Among these cases, there are an estimated 95,000 deaths (uncertainty range: 21,000-143,000). Conclusion/Significance The global burden of cholera remains high. Sub-Saharan Africa accounts for the majority of this burden. Our findings can inform programmatic decision-making for cholera control. PMID:26043000
-
Rice bran protein hydrolysates attenuate diabetic nephropathy in diabetic animal model.
Boonloh, Kampeebhorn; Lee, Eun Soo; Kim, Hong Min; Kwon, Mi Hye; Kim, You Mi; Pannangpetch, Patchareewan; Kongyingyoes, Bunkerd; Kukongviriyapan, Upa; Thawornchinsombut, Supawan; Lee, Eun Young; Kukongviriyapan, Veerapol; Chung, Choon Hee
2018-03-01
Diabetic nephropathy (DN) is an important microvascular complication of uncontrolled diabetes. The features of DN include albuminuria, extracellular matrix alterations, and progressive renal insufficiency. Rice bran protein hydrolysates (RBPs) have been reported to have antihyperglycemic, lipid-lowering, and anti-inflammatory effects in diabetic rats. Our study was to investigate the renoprotective effects of RBP in diabetic animals and mesangial cultured cells. Eight-week-old male db/m and db/db mice were orally treated with tap water or RBP (100 or 500 mg/kg/day) for 8 weeks. At the end of the experiment, diabetic nephropathy in kidney tissues was investigated for histological, ultrastructural, and clinical chemistry changes, and biomarkers of angiogenesis, fibrosis, inflammation, and antioxidant in kidney were analyzed by Western blotting. Protection against proangiogenic proteins and induction of cytoprotection by RBP in cultured mesangial cells was evaluated. RBP treatment improved insulin sensitivity, decreased elevated fasting serum glucose levels, and improved serum lipid levels and urinary albumin/creatinine ratios in diabetic mice. RBP ameliorated the decreases in podocyte slit pore numbers, thickening of glomerular basement membranes, and mesangial matrix expansion and suppressed elevation of MCP-1, ICAM-1, HIF-1α, VEGF, TGF-β, p-Smad2/3, and type IV collagen expression. Moreover, RBP restored suppressed antioxidant Nrf2 and HO-1 expression. In cultured mesangial cells, RBP inhibited high glucose-induced angiogenic protein expression and induced the expression of Nrf2 and HO-1. RBP attenuates the progression of diabetic nephropathy and restored renal function by suppressing the expression of proangiogenic and profibrotic proteins, inhibiting proinflammatory mediators, and restoring the antioxidant and cytoprotective system.
-
APOL1 Nephropathy: A Population Genetics and Evolutionary Medicine Detective Story.
Kruzel-Davila, Etty; Wasser, Walter G; Skorecki, Karl
2017-11-01
Common DNA sequence variants rarely have a high-risk association with a common disease. When such associations do occur, evolutionary forces must be sought, such as in the association of apolipoprotein L1 (APOL1) gene risk variants with nondiabetic kidney diseases in populations of African ancestry. The variants originated in West Africa and provided pathogenic resistance in the heterozygous state that led to high allele frequencies owing to an adaptive evolutionary selective sweep. However, the homozygous state is disadvantageous and is associated with a markedly increased risk of a spectrum of kidney diseases encompassing hypertension-attributed kidney disease, focal segmental glomerulosclerosis, human immunodeficiency virus nephropathy, sickle cell nephropathy, and progressive lupus nephritis. This scientific success story emerged with the help of the tools developed over the past 2 decades in human genome sequencing and population genomic databases. In this introductory article to a timely issue dedicated to illuminating progress in this area, we describe this unique population genetics and evolutionary medicine detective story. We emphasize the paradox of the inheritance mode, the missing heritability, and unresolved associations, including cardiovascular risk and diabetic nephropathy. We also highlight how genetic epidemiology elucidates mechanisms and how the principles of evolution can be used to unravel conserved pathways affected by APOL1 that may lead to novel therapies. The APOL1 gene provides a compelling example of a common variant association with common forms of nondiabetic kidney disease occurring in a continental population isolate with subsequent global admixture. Scientific collaboration using multiple experimental model systems and approaches should further clarify pathomechanisms further, leading to novel therapies. Copyright © 2017 Elsevier Inc. All rights reserved.
-
Loss of TIMP3 underlies diabetic nephropathy via FoxO1/STAT1 interplay.
Fiorentino, Loredana; Cavalera, Michele; Menini, Stefano; Marchetti, Valentina; Mavilio, Maria; Fabrizi, Marta; Conserva, Francesca; Casagrande, Viviana; Menghini, Rossella; Pontrelli, Paola; Arisi, Ivan; D'Onofrio, Mara; Lauro, Davide; Khokha, Rama; Accili, Domenico; Pugliese, Giuseppe; Gesualdo, Loreto; Lauro, Renato; Federici, Massimo
2013-03-01
ADAM17 and its inhibitor TIMP3 are involved in nephropathy, but their role in diabetic kidney disease (DKD) is unclear. Diabetic Timp3(-/-) mice showed increased albuminuria, increased membrane thickness and mesangial expansion. Microarray profiling uncovered a significant reduction of Foxo1 expression in diabetic Timp3(-/-) mice compared to WT, along with FoxO1 target genes involved in autophagy, while STAT1, a repressor of FoxO1 transcription, was increased. Re-expression of Timp3 in Timp3(-/-) mesangial cells rescued the expression of Foxo1 and its targets, and decreased STAT1 expression to control levels; abolishing STAT1 expression led to a rescue of FoxO1, evoking a role of STAT1 in linking Timp3 deficiency to FoxO1. Studies on kidney biopsies from patients with diabetic nephropathy confirmed a significant reduction in TIMP3, FoxO1 and FoxO1 target genes involved in autophagy compared to controls, while STAT1 expression was strongly increased. Our study suggests that loss of TIMP3 is a hallmark of DKD in human and mouse models and designates TIMP3 as a new possible therapeutic target for diabetic nephropathy. Copyright © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.
-
Deek, Hiba; Newton, Phillip; Sheerin, Noella; Noureddine, Samar; Davidson, Patricia M
2014-11-01
Contrast media induced nephropathy (CIN) is a sudden compromise of renal function 24-48 h after administering contrast medium during a CT scan or angiography. CIN accounts for 10% of hospital acquired renal failure and is ranked the third cause of acquiring this condition. Identifying patients at risk through proper screening can reduce the occurrence of this condition. This review paper aims to critique current evidence, provide a better understanding of CIN, inform nursing practice and make recommendations for bedside nurses and future research. An integrative review of the literature was made using the key terms: "contrast media", "nephritis", "nephropathy", "contrast media induced nephropathy scores", "acute kidney failure", "acute renal failure" and "acute kidney injury". MeSH key terms used in some databases were: "prevention and control", "acute kidney failure" and "treatment". Databases searched included Medline, CINAHL and Academic Search Complete, and references of relevant articles were also assessed. The search included all articles between the years 2000 and 2013. Sixty-seven articles were obtained as a result of the search, including RCTs, systematic reviews, and retrospective studies. Contrast media induced nephropathy is an iatrogenic complication occurring secondary to diagnostic or therapeutic procedures. At times it is unavoidable but a systematic method of risk assessment should be adopted to identify high risk patients for tailored and targeted approaches to management interventions. As the use of contrast media is increasing for diagnostic purposes, it is important that nurses be aware of the risk factors for CIN, identify and monitor high risk patients to prevent deterioration in renal function when possible. Copyright © 2014 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.
-
Semaphorin3a Promotes Advanced Diabetic Nephropathy
Aggarwal, Pardeep K.; Veron, Delma; Thomas, David B.; Siegel, Dionicio; Moeckel, Gilbert; Kashgarian, Michael
2015-01-01
The onset of diabetic nephropathy (DN) is highlighted by glomerular filtration barrier abnormalities. Identifying pathogenic factors and targetable pathways driving DN is crucial to developing novel therapies and improving the disease outcome. Semaphorin3a (sema3a) is a guidance protein secreted by podocytes. Excess sema3a disrupts the glomerular filtration barrier. Here, using immunohistochemistry, we show increased podocyte SEMA3A in renal biopsies from patients with advanced DN. Using inducible, podocyte-specific Sema3a gain-of-function (Sema3a+) mice made diabetic with streptozotocin, we demonstrate that sema3a is pathogenic in DN. Diabetic Sema3a+ mice develop massive proteinuria, renal insufficiency, and extensive nodular glomerulosclerosis, mimicking advanced DN in humans. In diabetic mice, Sema3a+ exacerbates laminin and collagen IV accumulation in Kimmelstiel-Wilson-like glomerular nodules and causes diffuse podocyte foot process effacement and F-actin collapse via nephrin, αvβ3 integrin, and MICAL1 interactions with plexinA1. MICAL1 knockdown and sema3a inhibition render podocytes not susceptible to sema3a-induced shape changes, indicating that MICAL1 mediates sema3a-induced podocyte F-actin collapse. Moreover, sema3a binding inhibition or podocyte-specific plexinA1 deletion markedly ameliorates albuminuria and abrogates renal insufficiency and the diabetic nodular glomerulosclerosis phenotype of diabetic Sema3a+ mice. Collectively, these findings indicate that excess sema3a promotes severe diabetic nephropathy and identifies novel potential therapeutic targets for DN. PMID:25475434
-
Diabetic nephropathy and antioxidants.
Tavafi, Majid
2013-01-01
Oxidative stress has crucial role in pathogenesis of diabetic nephropathy (DN). Despite satisfactory results from antioxidant therapy in rodent, antioxidant therapy showed conflicting results in combat with DN in diabetic patients. Directory of Open Access Journals (DOAJ), Google Scholar,Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. Treatment of DN in human are insufficient with rennin angiotensin system (RAS) blockers, so additional agent ought to combine with this management. Meanwhile based on DN pathogenesis and evidences in experimental and human researches, the antioxidants are the best candidate. New multi-property antioxidants may be improved human DN that show high power antioxidant capacity, long half-life time, high permeability to mitochondrion, improve body antioxidants enzymes activity and anti-inflammatory effects. Based on this review and our studies on diabetic rats, rosmarinic acid a multi-property antioxidant may be useful in DN patients, but of course, needs to be proven in clinical trials studies.
-
Tanji, N; Markowitz, G S; Fu, C; Kislinger, T; Taguchi, A; Pischetsrieder, M; Stern, D; Schmidt, A M; D'Agati, V D
2000-09-01
Advanced glycation end products (AGE) contribute to diabetic tissue injury by two major mechanisms, i.e., the alteration of extracellular matrix architecture through nonenzymatic glycation, with formation of protein crosslinks, and the modulation of cellular functions through interactions with specific cell surface receptors, the best characterized of which is the receptor for AGE (RAGE). Recent evidence suggests that the AGE-RAGE interaction may also be promoted by inflammatory processes and oxidative cellular injury. To characterize the distributions of AGE and RAGE in diabetic kidneys and to determine their specificity for diabetic nephropathy, an immunohistochemical analysis of renal biopsies from patients with diabetic nephropathy (n = 26), hypertensive nephrosclerosis (n = 7), idiopathic focal segmental glomerulosclerosis (n = 11), focal sclerosis secondary to obesity (n = 7), and lupus nephritis (n = 11) and from normal control subjects (n = 2) was performed, using affinity-purified antibodies raised to RAGE and two subclasses of AGE, i.e., N(epsilon)-(carboxymethyl)-lysine (CML) and pentosidine (PENT). AGE were detected equally in diffuse and nodular diabetic nephropathy. CML was the major AGE detected in diabetic mesangium (96%), glomerular basement membranes (GBM) (42%), tubular basement membranes (85%), and vessel walls (96%). In diabetic nephropathy, PENT was preferentially located in interstitial collagen (90%) and was less consistently observed in vessel walls (54%), mesangium (77%), GBM (4%), and tubular basement membranes (31%). RAGE was expressed on normal podocytes and was upregulated in diabetic nephropathy. The restriction of RAGE mRNA expression to glomeruli was confirmed by reverse transcription-PCR analysis of microdissected renal tissue compartments. The extent of mesangial and GBM immunoreactivity for CML, but not PENT, was correlated with the severity of diabetic glomerulosclerosis, as assessed pathologically. CML and PENT were also
-
Sessa, Maurizio; Rossi, Claudia; Mascolo, Annamaria; Scavone, Cristina; di Mauro, Gabriella; Grassi, Roberto; Sportiello, Liberata; Cappabianca, Salvatore; Rafaniello, Concetta
2017-01-01
The use of contrast media in Italy has exponentially increased in the past 3 decades. However, it is unknown whether there has been an increase in clinical research evaluating the risks associated with contrast media usage, especially regarding contrast-induced nephropathy. To fill this gap in knowledge, we performed a systematic review. Meta-analyses, observational studies, and clinical trials assessing contrast media-induced nephropathy as the safety outcome, in which at least one author was affiliated with an Italian university/health care structure, were eligble. Ovid MEDLINE, Ovid Embase, Cochrane Methodology Register, and Web of Science were screened. Men and women exposed to contrast media. In total, 60 original articles were retrieved with an incremental trend between 1990 and 2017. Cohort studies were the most common study design represented. In total, 45 of 60 (75.0%) studies were monocenter studies and 41 of 60 (68.3%) received no funding. In all, 91.7% of studies disclosed no conflicts of interest and 81.7% had no external collaboration. Most of the studies provided a level of evidence of III-2 (32/60; 53.3%) and II (23/60; 38.3%). In total, 50 of 60 studies (83.3%) were published in a scientific journal ranked in the first quartile of their subject area. There was an increased number of studies evaluating contrast-induced nephropathy in Italy during the last three decades. These studies covered procedures to prevent contrast-induced nephropathy or aimed to identify risk factors, biomarkers, and scores, and their related prognosis.
-
Wysocki, Jan; Ye, Minghao; Khattab, Ahmed M.; Fogo, Agnes; Martin, Aline; David, Nicolae Valentin; Kanwar, Yashpal; Osborn, Mark; Batlle, Daniel
2016-01-01
Blockers of the renin-angiotensin system are effective in the treatment of experimental and clinical diabetic nephropathy. An approach different from blocking the formation or action of angiotensin II(1-8) that could also be effective involves fostering its degradation. Angiotensin converting enzyme 2 (ACE2) is a monocarboxypeptidase than cleaves angiotensin II (1-8) to form angiotensin (1-7). Therefore, we examined the renal effects of murine recombinant ACE2 in mice with streptozotocin-induced diabetic nephropathy as well as that of amplification of circulating ACE2 using minicircle DNA delivery prior to induction of experimental diabetes. This delivery resulted in a long-term sustained and profound increase in serum ACE2 activity and enhanced ability to metabolize an acute angiotensin II (1-8) load. In mice with streptozotocin-induced diabetes pretreated with minicircle ACE2, ACE2 protein in plasma increased markedly and this was associated with a more than 100-fold increase in serum ACE2 activity. However, minicircle ACE2 did not result in changes in urinary ACE2 activity as compared to untreated diabetic mice. In both diabetic groups, glomerular filtration rate increased significantly and to the same extent as compared to non-diabetic controls. Albuminuria, glomerular mesangial expansion, glomerular cellularity and glomerular size, were all increased to a similar extent in minicircle ACE2-treated and untreated diabetic mice, as compared to non-diabetic controls. Recombinant mouse ACE2 given for 4 weeks by intraperitoneal daily injections in mice with streptozotocin-induced diabetic nephropathy also failed to improve albuminuria or kidney pathology. Thus, a profound augmentation of ACE2 confined to the circulation failed to ameliorate the glomerular lesions and hyperfiltration characteristic of early diabetic nephropathy. These findings emphasize the importance of targeting the kidney rather than the circulatory renin angiotensin system to combat diabetic
-
Efficacy of low-dose oral sulodexide in the management of diabetic nephropathy.
Blouza, Samira; Dakhli, Sabeur; Abid, Hafaoua; Aissaoui, Mohamed; Ardhaoui, Ilhem; Ben Abdallah, Nejib; Ben Brahim, Samir; Ben Ghorbel, Imed; Ben Salem, Nabila; Beji, Soumaya; Chamakhi, Said; Derbel, Adnene; Derouiche, Fethi; Djait, Faycal; Doghri, Taieb; Fourti, Yamina; Gharbi, Faycel; Jellouli, Kamel; Jellazi, Nabil; Kamoun, Kamel; Khedher, Adel; Letaief, Amel; Limam, Ridha; Mekaouer, Awatef; Miledi, Riadh; Nagati, Khemaies; Naouar, Meriem; Sellem, Sami; Tarzi, Hichem; Turki, Selma; Zidi, Borni; Achour, Abdellatif
2010-01-01
Diabetic nephropathy (DN) is the single greatest cause of end-stage renal disease (ESRD). Without specific interventions, microalbuminuria (incipient nephropathy) gradually progresses to macroalbuminuria (overt nephropathy) within 10-15 years in about 80% of type 1 and 30% of type 2 diabetic patients, and to ESRD within further 20 years in about 75% and 20%, respectively. A primary alteration in DN consists of decreased concentration of glycosaminoglycans (GAGs) in the glomerular extracellular matrix. This evidence has prompted interest in using exogenous GAGs and specifically sulodexide in DN treatment. In this uncontrolled multicenter study, diabetic patients with albumin excretion rate (AER) >or=30 mg/24 hours were treated with oral sulodexide 50 mg/day for 6 months, while receiving concomitant medication as required. Two hundred thirty-seven patients (54% males and 46% females, mean age 55 years, mean diabetes duration 11 years) were evaluated; 89% had type 2 and 11% type 1 diabetes mellitus, 67% microalbuminuria and 33% macroalbuminuria. AER was significantly and progressively reduced during sulodexide treatment (p<0.0001): geometric mean after 3 and 6 months was 63.7% (95% confidence interval [95% CI], 59.3%-68.4%) and 42.7% (95% CI, 37.8%-48.2%) of baseline, respectively. The reduction was similar in type 1 and type 2 diabetes and was slightly greater in macroalbuminuric than in microalbuminuric patients. Blood pressure was slightly lowered, while fasting glucose and glycosylated hemoglobin were moderately reduced. Adverse effects were observed in 5.5% of patients, including gastrointestinal in 3.8%. Sulodexide therapy was shown to reduce AER in patients with DN.
-
Long-Term Outcomes in Idiopathic Membranous Nephropathy Using a Restrictive Treatment Strategy
van Dijk, Peter R.; Hofstra, Julia M.; Wetzels, Jack F.M.
2014-01-01
Recently published Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend limiting the use of immunosuppressive drugs in idiopathic membranous nephropathy to patients at the highest risk of kidney failure. However, recommendations are based on natural history rather than direct assessment of a restrictive treatment strategy. Here, we describe the long-term outcomes of treating a large cohort of patients with idiopathic membranous nephropathy according to a restrictive treatment policy. We analyzed data for 254 patients who visited our outpatient clinic between 1995 and 2009. All patients were treated with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Immunosuppressive therapy was recommended in cases of deteriorating renal function or untreatable nephrotic syndrome. Primary outcomes for the present study were renal replacement therapy and death. Secondary outcomes included adverse events during follow-up and remission of proteinuria. In total, 124 patients (49%) received immunosuppressive therapy, which predominantly consisted of cyclophosphamide combined with steroids. Ten-year cumulative incidence rates were 3% for renal replacement therapy and 10% for death. Partial remission rates were 39%, 70%, and 83% after 1, 3, and 5 years, respectively; complete remission rates were 5%, 24%, and 38% at 1, 3, and 5 years, respectively. A serious adverse event occurred in 23% of all patients. The most notable complications were infections (17%), leukopenia (18%), cardiovascular events (13%), and malignancies (8%). In conclusion, the use of a restrictive treatment strategy in this cohort of patients with idiopathic membranous nephropathy yielded favorable outcomes while limiting the number of patients exposed to toxic drugs. These results support current KDIGO guidelines. PMID:24029426
-
A GENOME WIDE ASSOCIATION STUDY FOR DIABETIC NEPHROPATHY GENES IN AFRICAN AMERICANS
McDonough, Caitrin W.; Palmer, Nicholette D.; Hicks, Pamela J.; Roh, Bong H.; An, S. Sandy; Cooke, Jessica N.; Hester, Jessica M.; Wing, Maria R.; Bostrom, Meredith A.; Rudock, Megan E.; Lewis, Joshua P.; Talbert, Matthew E.; Blevins, Rebecca A.; Lu, Lingyi; Ng, Maggie C.Y.; Sale, Michele M.; Divers, Jasmin; Langefeld, Carl D.; Freedman, Barry I.; Bowden, Donald W.
2011-01-01
A genome-wide association study was performed using the Affymetrix 6.0 chip to identify genes associated with diabetic nephropathy in African Americans. Association analysis was performed adjusting for admixture in 965 type 2 diabetic African American patients with end-stage renal disease (ESRD) and in 1029 African Americans without type 2 diabetes or kidney disease as controls. The top 724 single nucleotide polymorphisms (SNPs) with evidence of association to diabetic nephropathy were then genotyped in a replication sample of an additional 709 type 2 diabetes-ESRD patients and 690 controls. SNPs with evidence of association in both the original and replication studies were tested in additional African American cohorts consisting of 1246 patients with type 2 diabetes without kidney disease and 1216 with non-diabetic ESRD to differentiate candidate loci for type 2 diabetes-ESRD, type 2 diabetes, and/or all-cause ESRD. Twenty-five SNPs were significantly associated with type 2 diabetes-ESRD in the genome-wide association and initial replication. Although genome-wide significance with type 2 diabetes was not found for any of these 25 SNPs, several genes, including RPS12, LIMK2, and SFI1 are strong candidates for diabetic nephropathy. A combined analysis of all 2890 patients with ESRD showed significant association SNPs in LIMK2 and SFI1 suggesting that they also contribute to all-cause ESRD. Thus, our results suggest that multiple loci underlie susceptibility to kidney disease in African Americans with type 2 diabetes and some may also contribute to all-cause ESRD. PMID:21150874
-
A genome-wide association study for diabetic nephropathy genes in African Americans.
McDonough, Caitrin W; Palmer, Nicholette D; Hicks, Pamela J; Roh, Bong H; An, S Sandy; Cooke, Jessica N; Hester, Jessica M; Wing, Maria R; Bostrom, Meredith A; Rudock, Megan E; Lewis, Joshua P; Talbert, Matthew E; Blevins, Rebecca A; Lu, Lingyi; Ng, Maggie C Y; Sale, Michele M; Divers, Jasmin; Langefeld, Carl D; Freedman, Barry I; Bowden, Donald W
2011-03-01
A genome-wide association study was performed using the Affymetrix 6.0 chip to identify genes associated with diabetic nephropathy in African Americans. Association analysis was performed adjusting for admixture in 965 type 2 diabetic African American patients with end-stage renal disease (ESRD) and in 1029 African Americans without type 2 diabetes or kidney disease as controls. The top 724 single nucleotide polymorphisms (SNPs) with evidence of association to diabetic nephropathy were then genotyped in a replication sample of an additional 709 type 2 diabetes-ESRD patients and 690 controls. SNPs with evidence of association in both the original and replication studies were tested in additional African American cohorts consisting of 1246 patients with type 2 diabetes without kidney disease and 1216 with non-diabetic ESRD to differentiate candidate loci for type 2 diabetes-ESRD, type 2 diabetes, and/or all-cause ESRD. Twenty-five SNPs were significantly associated with type 2 diabetes-ESRD in the genome-wide association and initial replication. Although genome-wide significance with type 2 diabetes was not found for any of these 25 SNPs, several genes, including RPS12, LIMK2, and SFI1 are strong candidates for diabetic nephropathy. A combined analysis of all 2890 patients with ESRD showed significant association SNPs in LIMK2 and SFI1 suggesting that they also contribute to all-cause ESRD. Thus, our results suggest that multiple loci underlie susceptibility to kidney disease in African Americans with type 2 diabetes and some may also contribute to all-cause ESRD.
-
Clinical and pathological analysis of IgA nephropathy with chronic renal failure.
Liu, Yuyuan; Hu, Qinfeng; Shen, Ping; Tang, Li; Yuan, Gang; Zhou, Yongmei; Chai, Huaqi
2016-10-01
To investigative clinical and pathological characteristics of IgA nephropathy with chronic renal failure. Clinical and pathological findings from 65 cases of IgA nephropathy with chronic renal failure were reviewed. Pathological characteristics of all the cases were analyzed according to WHO definition and Oxford Classification. Evaluating the severity of pathological lesions by the Katafuchi R semiquantitative scoring system, and analyzing their relationship with clinical indexes of renal function. Of all 65 cases the male and female ratio was 1.4, and the mean age was 37 ± 13 years old. Levels of systolic pressure, mean arterial pressure (MAP), blood urea nitrogen (BUN), serum creatinine (Scr), uric acid (UA), album (Alb), serum IgG and 24 h urinary protein were related with eGRF level (p < 0.05, respectively). The most common pathological type was proliferative sclerosis glomerulonephritis (PSGN) and M1S1E0T0 according to WHO definition and Oxford Classification, respectively, and most of the 65 cases had glomerulosclerosis. Simple IgA deposition was the most common immunopathologic type. Of all the cases, 44.6% accompanied with C3 while 4.6% with C1q. Further analysis revealed there were no relationships between severity of pathological lesion and levels of clinical indexes (Scr and eGRF) (p > 0.05). IgA nephropathy with chronic renal failure usually occurred in young adults, and it had severe clinical condition and pathological changes, while there was no significant relationship between them.
-
Population health and status of epidemiology in Western European, Balkan and Baltic countries.
Seniori Costantini, Adele; Gallo, Federica; Pega, Frank; Saracci, Rodolfo; Veerus, Piret; West, Robert
2015-02-01
This article is part of a series commissioned by the International Epidemiological Association, aimed at describing population health and epidemiological resources in the six World Health Organization (WHO) regions. It covers 32 of the 53 WHO European countries, namely the Western European countries, the Balkan countries and the Baltic countries. The burdens of mortality and morbidity and the patterns of risk factors and inequalities have been reviewed in order to identify health priorities and challenges. Literature and internet searches were conducted to stock-take epidemiological teaching, research activities, funding and scientific productivity. These countries have among the highest life expectancies worldwide. However, within- and between-country inequalities persist, which are largely due to inequalities in distribution of main health determinants. There is a long tradition of epidemiological research and teaching in most countries, in particular in the Western European countries. Cross-national networks and collaborations are increasing through the support of the European Union which fosters procedures to standardize educational systems across Europe and provides funding for epidemiological research through framework programmes. The number of Medline-indexed epidemiological research publications per year led by Western European countries has been increasing. The countries accounts for nearly a third of the global epidemiological publication. Although population health has improved considerably overall, persistent within- and between-country inequalities continue to challenge national and European health institutions. More research, policy and action on the social determinants of health are required in the region. Epidemiological training, research and workforce in the Baltic and Balkan countries should be strengthened. European epidemiologists can play pivotal roles and must influence legislation concerning production and access to high-quality data. © The
-
Yamanouchi, Masayuki; Hoshino, Junichi; Ubara, Yoshifumi; Takaichi, Kenmei; Kinowaki, Keiichi; Fujii, Takeshi; Ohashi, Kenichi; Mise, Koki; Toyama, Tadashi; Hara, Akinori; Kitagawa, Kiyoki; Shimizu, Miho; Furuichi, Kengo; Wada, Takashi
2018-01-01
There have been a limited number of biopsy-based studies on diabetic nephropathy, and therefore the clinical importance of renal biopsy in patients with diabetes in late-stage chronic kidney disease (CKD) is still debated. We aimed to clarify the renal prognostic value of pathological information to clinical information in patients with diabetes and advanced CKD. We retrospectively assessed 493 type 2 diabetics with biopsy-proven diabetic nephropathy in four centers in Japan. 296 patients with stage 3-5 CKD at the time of biopsy were identified and assigned two risk prediction scores for end-stage renal disease (ESRD): the Kidney Failure Risk Equation (KFRE, a score composed of clinical parameters) and the Diabetic Nephropathy Score (D-score, a score integrated pathological parameters of the Diabetic Nephropathy Classification by the Renal Pathology Society (RPS DN Classification)). They were randomized 2:1 to development and validation cohort. Hazard Ratios (HR) of incident ESRD were reported with 95% confidence interval (CI) of the KFRE, D-score and KFRE+D-score in Cox regression model. Improvement of risk prediction with the addition of D-score to the KFRE was assessed using c-statistics, continuous net reclassification improvement (NRI), and integrated discrimination improvement (IDI). During median follow-up of 1.9 years, 194 patients developed ESRD. The cox regression analysis showed that the KFRE,D-score and KFRE+D-score were significant predictors of ESRD both in the development cohort and in the validation cohort. The c-statistics of the D-score was 0.67. The c-statistics of the KFRE was good, but its predictive value was weaker than that in the miscellaneous CKD cohort originally reported (c-statistics, 0.78 vs. 0.90) and was not significantly improved by adding the D-score (0.78 vs. 0.79, p = 0.83). Only continuous NRI was positive after adding the D-score to the KFRE (0.4%; CI: 0.0-0.8%). We found that the predict values of the KFRE and the D-score were
-
Hepatitis a virus genotypes and strains from an endemic area of Europe, Bulgaria 2012-2014.
Bruni, Roberto; Taffon, Stefania; Equestre, Michele; Cella, Eleonora; Lo Presti, Alessandra; Costantino, Angela; Chionne, Paola; Madonna, Elisabetta; Golkocheva-Markova, Elitsa; Bankova, Diljana; Ciccozzi, Massimo; Teoharov, Pavel; Ciccaglione, Anna Rita
2017-07-14
Hepatitis A virus (HAV) infection is endemic in Eastern European and Balkan region countries. In 2012, Bulgaria showed the highest rate (67.13 cases per 100,000) in Europe. Nevertheless, HAV genotypes and strains circulating in this country have never been described. The present study reports the molecular characterization of HAV from 105 patients from Bulgaria. Anti-HAV IgM positive serum samples collected in 2012-2014 from different towns and villages in Bulgaria were analysed by nested RT-PCR, sequencing of the VP1/2A region and phylogenetic analysis; the results were analysed together with patient and geographical data. Phylogenetic analysis revealed two main sequence groups corresponding to the IA (78/105, 74%) and IB (27/105, 26%) sub-genotypes. In the IA group, a major and a minor cluster were observed (62 and 16 sequences, respectively). Most sequences from the major cluster (44/62, 71%) belonged to either of two strains, termed "strain 1" and "strain 2", differing only for a single specific nucleotide; the remaining sequences (18/62, 29%) showed few (1 to 4) nucleotide variations respect to strain 1 and 2. Strain 2 is identical to the strain previously responsible for an outbreak in the Czech Republic in 2008 and a large multi-country European outbreak caused by contaminated mixed frozen berries in 2013. Most sequences of the IA minor cluster and the IB group were detected in large/medium centers (LMCs). Overall, sequences from the IA major cluster were more frequent in small centers (SCs), but strain 1 and strain 2 showed an opposite relative frequency in SCs and LMCs (strain 1 more frequent in SCs, strain 2 in LMCs). Genotype IA predominated in Bulgaria in 2012-2014 and phylogenetic analysis identified a major cluster of highly related or identical IA sequences, representing 59% of the analysed cases; these isolates were mostly detected in SCs, in which HAV shows higher endemicity than in LMCs. The distribution of viral sequences suggests the existence
-
Zhang, YingHui; Wang, Bing; Guo, Feng; Li, ZhiZhen; Qin, GuiJun
2018-06-14
Diabetic nephropathy is one of the manifestations of systemic microangiopathy in diabetes. Hesperetin, a natural flavanone glycoside compound in citrus fruits, has been demonstrated to exert hypoglycemic effects and protect kidney in experimental diabetic animals. The current study was aimed to investigate the mechanisms underlying the hypoglycemic effects of hesperetin in high-fat/streptozocin (STZ)-induced diabetic nephropathy. The results showed that mice in whom hesperetin was administered for 4 weeks attenuated the increased fasting blood glucose and impaired glucose tolerance ability that was observed in high-fat/STZ mice. In addition, we found that hesperetin ameliorated the abnormalities of biochemical parameters in serum, liver, and kidney of mice with diabetic nephropathy. Hesperetin also rescued the irregular distortions in glomerular basement membrane and expanded mesangial regions. Moreover, hesperetin repaired the function of podocyte by increasing renal nephrin expression and decreasing renal alpha-smooth muscle actin expression. Furthermore, hesperetin inhibited the expression of transforming growth factor-β1 (TGF-β1) and its downstream effectors integrin-linked kinase (ILK) and Akt. In conclusion, our study implies that hesperetin produced protective effects in diabetic nephropathy possibly by suppressing TGF-β1-ILK-Akt signaling. Copyright © 2018 Elsevier Masson SAS. All rights reserved.
-
Mesoamerican nephropathy: a neglected tropical disease with an infectious etiology?
Murray, Kristy O; Fischer, Rebecca S B; Chavarria, Denis; Duttmann, Christiane; Garcia, Melissa N; Gorchakov, Rodion; Hotez, Peter J; Jiron, William; Leibler, Jessica H; Lopez, Job E; Mandayam, Sreedhar; Marin, Alejandro; Sheleby, Jessica
2015-10-01
An outbreak of unexplained and severe kidney disease, "Mesoamerican Nephropathy," in mostly young, male sugar cane workers emerged in Central America in the late 1990's. As a result, an estimated 20,000 individuals have died, to date. Unfortunately, and with great consequence to human life, the etiology of the outbreak has yet to be identified. The sugarcane fields in Chichigalpa, Chinandega, Nicaragua, have been involved in the outbreak, and during our initial investigation, we interviewed case patients who experienced fever, nausea and vomiting, arthralgia, myalgia, headache, neck and back pain, weakness, and paresthesia at the onset of acute kidney disease. We also observed a heavy infestation of rodents, particularly of Sigmodon species, in the sugarcane fields. We hypothesize that infectious pathogens are being shed through the urine and feces of these rodents, and workers are exposed to these pathogens during the process of cultivating and harvesting sugarcane. In this paper, we will discuss the epidemic in the Chichigalpa area, potential pathogens responsible for Mesoamerican Nephropathy, and steps needed in order to diagnose, treat, and prevent future cases from occurring. Copyright © 2015 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
-
Idiopathic membranous nephropathy: outline and rationale of a treatment strategy.
du Buf-Vereijken, Peggy W G; Branten, Amanda J W; Wetzels, Jack F M
2005-12-01
Idiopathic membranous nephropathy is a common cause of nephrotic syndrome. The treatment of patients with idiopathic membranous nephropathy is heavily debated. Based on literature data and our own experience, we propose a rational treatment strategy. Patients with renal insufficiency (serum creatinine level > 1.5 mg/dL [> 135 micromol/L]) are at greatest risk for the development of end-stage renal disease and should receive immunosuppressive therapy. In patients with normal renal function (serum creatinine level < 1.5 mg/dL [< 135 micromol/L]), risk for developing end-stage renal disease can be estimated by measuring urinary excretion of beta2-microglobulin or alpha1-microglobulin and immunoglobulin G. For low-risk patients, a wait-and-see policy is advised. High-risk patients likely benefit from immunosuppressive therapy. Currently, combinations of steroids with chlorambucil or cyclophosphamide are the best studied. We prefer cyclophosphamide in view of its fewer side effects. Cyclosporine may be an alternative option in patients with well-preserved renal function, although long-term data are lacking. Other immunosuppressive agents, such as mycophenolate mofetil or rituximab, currently are under study; however, data are insufficient to support their routine use.
-
Fervenza, Fernando C; Canetta, Pietro A; Barbour, Sean J; Lafayette, Richard A; Rovin, Brad H; Aslam, Nabeel; Hladunewich, Michelle A; Irazabal, Maria V; Sethi, Sanjeev; Gipson, Debbie S; Reich, Heather N; Brenchley, Paul; Kretzler, Matthias; Radhakrishnan, Jai; Hebert, Lee A; Gipson, Patrick E; Thomas, Leslie F; McCarthy, Ellen T; Appel, Gerald B; Jefferson, J Ashley; Eirin, Alfonso; Lieske, John C; Hogan, Marie C; Greene, Eddie L; Dillon, John J; Leung, Nelson; Sedor, John R; Rizk, Dana V; Blumenthal, Samuel S; Lasic, Lada B; Juncos, Luis A; Green, Dollie F; Simon, James; Sussman, Amy N; Philibert, David; Cattran, Daniel C
2015-01-01
Idiopathic membranous nephropathy remains the leading cause of nephrotic syndrome in Caucasian adults. Immunosuppressive therapy with cyclosporine (CSA) is often successful in reducing proteinuria, but its use is associated with a high relapse rate. Rituximab, a monoclonal antibody that specifically targets CD20 on the surface of B-cells, is effective in achieving a complete remission of proteinuria in patients with idiopathic membranous nephropathy. However, whether rituximab is as effective as CSA in inducing and maintaining complete or partial remission of proteinuria in these patients is unknown. The membranous nephropathy trial of rituximab (MENTOR) hypothesizes that B-cell targeting with rituximab is non-inferior to CSA in inducing long-term remission of proteinuria. Patients with idiopathic membranous nephropathy, proteinuria ≥5 g/24 h, and a minimum of 3 months of Angiotensin-II blockade will be randomized into a 12-month treatment period with i.v. rituximab, 1,000 mg (2 infusions, 14 days apart; repeated at 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months) or oral CSA 3.5-5 mg/kg/day for 6 months (continued for another 6 months if a substantial reduction in proteinuria (equal to or >25%) is seen at 6 months). The efficacy of treatment will be assessed by the remission status (based on changes in proteinuria) at 24 months from randomization. Patient safety will be assessed via collection of adverse event data and evaluation of pre- and posttreatment laboratory data. At the 6-month post-randomization visit, patients who have been randomized to either CSA or rituximab but who do not have a reduction in proteinuria ≥25% (confirmed on repeat measurements within 2 weeks) will be considered treatment failures and exit the study. This study will test for the first time whether treatment with rituximab is non-inferior to CSA in inducing long-term remission (complete or partial) of proteinuria in patients with idiopathic
-
Lafayette, Richard A.; Canetta, Pietro A.; Rovin, Brad H.; Appel, Gerald B.; Novak, Jan; Nath, Karl A.; Sethi, Sanjeev; Tumlin, James A.; Mehta, Kshama; Hogan, Marie; Erickson, Stephen; Julian, Bruce A.; Leung, Nelson; Enders, Felicity T.; Brown, Rhubell; Knoppova, Barbora; Hall, Stacy
2017-01-01
IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody–producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy–proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin–converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m2, to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8–2.4) mg/dl, and proteinuria was 2.1 (0.6–5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose–deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy. PMID:27821627
-
Lafayette, Richard A; Canetta, Pietro A; Rovin, Brad H; Appel, Gerald B; Novak, Jan; Nath, Karl A; Sethi, Sanjeev; Tumlin, James A; Mehta, Kshama; Hogan, Marie; Erickson, Stephen; Julian, Bruce A; Leung, Nelson; Enders, Felicity T; Brown, Rhubell; Knoppova, Barbora; Hall, Stacy; Fervenza, Fernando C
2017-04-01
IgA nephropathy frequently leads to progressive CKD. Although interest surrounds use of immunosuppressive agents added to standard therapy, several recent studies have questioned efficacy of these agents. Depleting antibody-producing B cells potentially offers a new therapy. In this open label, multicenter study conducted over 1-year follow-up, we randomized 34 adult patients with biopsy-proven IgA nephropathy and proteinuria >1 g/d, maintained on angiotensin-converting enzyme inhibitors or angiotensin receptor blockers with well controlled BP and eGFR<90 ml/min per 1.73 m 2 , to receive standard therapy or rituximab with standard therapy. Primary outcome measures included change in proteinuria and change in eGFR. Median baseline serum creatinine level (range) was 1.4 (0.8-2.4) mg/dl, and proteinuria was 2.1 (0.6-5.3) g/d. Treatment with rituximab depleted B cells and was well tolerated. eGFR did not change in either group. Rituximab did not alter the level of proteinuria compared with that at baseline or in the control group; three patients in each group had ≥50% reduction in level of proteinuria. Serum levels of galactose-deficient IgA1 or antibodies against galactose-deficient IgA1 did not change. In this trial, rituximab therapy did not significantly improve renal function or proteinuria assessed over 1 year. Although rituximab effectively depleted B cells, it failed to reduce serum levels of galactose-deficient IgA1 and antigalactose-deficient IgA1 antibodies. Lack of efficacy of rituximab, at least at this stage and severity of IgA nephropathy, may reflect a failure of rituximab to reduce levels of specific antibodies assigned salient pathogenetic roles in IgA nephropathy. Copyright © 2017 by the American Society of Nephrology.
-
Papadaki, Christina; Soulis, Konstantinos; Muñoz-Mas, Rafael; Martinez-Capel, Francisco; Zogaris, Stamatis; Ntoanidis, Lazaros; Dimitriou, Elias
2016-01-01
The climate change in the Mediterranean area is expected to have significant impacts on the aquatic ecosystems and particular in the mountain rivers and streams that often host important species such as the Salmo farioides, Karaman 1938. These impacts will most possibly affect the habitat availability for various aquatic species resulting to an essential alteration of the water requirements, either for dams or other water abstractions, in order to maintain the essential levels of ecological flow for the rivers. The main scope of this study was to assess potential climate change impacts on the hydrological patterns and typical biota for a south-western Balkan mountain river, the Acheloos. The altered flow regimes under different emission scenarios of the Intergovernmental Panel on Climate Change (IPCC) were estimated using a hydrological model and based on regional climate simulations over the study area. The Indicators of Hydrologic Alteration (IHA) methodology was then used to assess the potential streamflow alterations in the studied river due to predicted climate change conditions. A fish habitat simulation method integrating univariate habitat suitability curves and hydraulic modeling techniques were used to assess the impacts on the relationships between the aquatic biota and hydrological status utilizing a sentinel species, the West Balkan trout. The most prominent effects of the climate change scenarios depict severe flow reductions that are likely to occur especially during the summer flows, changing the duration and depressing the magnitude of the natural low flow conditions. Weighted Usable Area-flow curves indicated the limitation of suitable habitat for the native trout. Finally, this preliminary application highlighted the potential of science-based hydrological and habitat simulation approaches that are relevant to both biological quality elements (fish) and current EU Water policy to serve as efficient tools for the estimation of possible climate
-
Evolutionary Relationships of Endemic/Epidemic and Sylvatic Dengue Viruses
Wang, Eryu; Ni, Haolin; Xu, Renling; Barrett, Alan D. T.; Watowich, Stanley J.; Gubler, Duane J.; Weaver, Scott C.
2000-01-01
Endemic/epidemic dengue viruses (DEN) that are transmitted among humans by the mosquito vectors Aedes aegypti and Aedes albopictus are hypothesized to have evolved from sylvatic DEN strains that are transmitted among nonhuman primates in West Africa and Malaysia by other Aedes mosquitoes. We tested this hypothesis with phylogenetic studies using envelope protein gene sequences of both endemic/epidemic and sylvatic strains. The basal position of sylvatic lineages of DEN-1, -2, and -4 suggested that the endemic/epidemic lineages of these three DEN serotypes evolved independently from sylvatic progenitors. Time estimates for evolution of the endemic/epidemic forms ranged from 100 to 1,500 years ago, and the evolution of endemic/epidemic forms represents relatively recent events in the history of DEN evolution. Analysis of envelope protein amino acid changes predicted to have accompanied endemic/epidemic emergence suggested a role for domain III in adaptation to new mosquito and/or human hosts. PMID:10708439
-
Dekeyser, Manon; François, Hélène; Beaudreuil, Séverine; Durrbach, Antoine
2015-01-01
In renal transplantation, BK-virus (BKV)-associated nephropathy has emerged as a major complication, with a prevalence of 1–10% and graft loss in >50% of cases. BKV is a member of the polyomavirus family and rarely induces apparent clinical disease in the general population. However, replication of polyomaviruses, associated with significant organ disease, is observed in patients with acquired immunosuppression. Monitoring of specific immunity combined with viral load could be used to individually assess the risk of viral reactivation and virus control. We review the current knowledge on BKV-specific cellular immunity and, more specifically, in immunocompromised patients. In the future, immune-based therapies could allow us to treat and prevent BKV-associated nephropathy. PMID:26136745
-
A World Malaria Map: Plasmodium falciparum Endemicity in 2007
Hay, Simon I; Guerra, Carlos A; Gething, Peter W; Patil, Anand P; Tatem, Andrew J; Noor, Abdisalan M; Kabaria, Caroline W; Manh, Bui H; Elyazar, Iqbal R. F; Brooker, Simon; Smith, David L; Moyeed, Rana A; Snow, Robert W
2009-01-01
Background Efficient allocation of resources to intervene against malaria requires a detailed understanding of the contemporary spatial distribution of malaria risk. It is exactly 40 y since the last global map of malaria endemicity was published. This paper describes the generation of a new world map of Plasmodium falciparum malaria endemicity for the year 2007. Methods and Findings A total of 8,938 P. falciparum parasite rate (PfPR) surveys were identified using a variety of exhaustive search strategies. Of these, 7,953 passed strict data fidelity tests for inclusion into a global database of PfPR data, age-standardized to 2–10 y for endemicity mapping. A model-based geostatistical procedure was used to create a continuous surface of malaria endemicity within previously defined stable spatial limits of P. falciparum transmission. These procedures were implemented within a Bayesian statistical framework so that the uncertainty of these predictions could be evaluated robustly. The uncertainty was expressed as the probability of predicting correctly one of three endemicity classes; previously stratified to be an informative guide for malaria control. Population at risk estimates, adjusted for the transmission modifying effects of urbanization in Africa, were then derived with reference to human population surfaces in 2007. Of the 1.38 billion people at risk of stable P. falciparum malaria, 0.69 billion were found in Central and South East Asia (CSE Asia), 0.66 billion in Africa, Yemen, and Saudi Arabia (Africa+), and 0.04 billion in the Americas. All those exposed to stable risk in the Americas were in the lowest endemicity class (PfPR2−10 ≤ 5%). The vast majority (88%) of those living under stable risk in CSE Asia were also in this low endemicity class; a small remainder (11%) were in the intermediate endemicity class (PfPR2−10 > 5 to < 40%); and the remaining fraction (1%) in high endemicity (PfPR2−10 ≥ 40%) areas. High endemicity was widespread in the
-
Mishra, Awanish; Bhatti, Rajbir; Singh, Amarjit; Singh Ishar, Mohan Paul
2010-03-01
The current study was designed to evaluate the ameliorative effect of the cinnamon oil upon early stage diabetic nephropathy owing to its antioxidant and antidiabetic effect. Cinnamon oil was extracted by hydro-distillation of the dried inner bark of Cinnamomum zeylanicum Blume. Further characterization of the extracted oil was carried out using IR, (1)H-NMR, and (13)C-NMR techniques. Early stage of diabetic nephropathy was induced by administration of alloxan (150 mg/kg, I. P.). Cinnamon oil was administered at varying doses (5, 10, 20 mg/kg; I. P.) while the level of fasting blood glucose, total cholesterol, high density lipoprotein, urea, thiobarbituric acid reactive substances, reduced glutathione, and catalase were determined. These parameters in cinnamon oil treated groups were compared with those of standard (glipizide; 10 mg/kg) and vehicle treated groups in order to investigate if cinnamon oil confers a significant protection against diabetic nephropathy. Histological studies of the kidney proved the protective effect of cinnamon oil by reducing the glomerular expansion, eradicating hyaline casts, and decreasing the tubular dilatations. Our results indicate that the volatile oil from cinnamon contains more than 98 % cinnamaldehyde and that it confers dose-dependent, significant protection against alloxan-induced renal damage, the maximum decrease in fasting blood glucose having been achieved at the dose of 20 mg/kg. (c) Georg Thieme Verlag KG Stuttgart . New York.
-
2013-12-01
AND BALKAN WARS ON THE REORGANIZATION AND MODERNIZATION OF THE OTTOMAN ARMY 5. FUNDING NUMBERS 6. AUTHOR( S ) Ali E. Topal 7. PERFORMING...MONITORING AGENCY NAME( S ) AND ADDRESS(ES) N/A 10. SPONSORING/MONITORING AGENCY REPORT NUMBER 11. SUPPLEMENTARY NOTES The views expressed in this...Erickson stresses the importance of military reform efforts supported by the GMC in his book: The world has taken very little note of the growth of
-
Climate threat on the Macaronesian endemic bryophyte flora.
Patiño, Jairo; Mateo, Rubén G; Zanatta, Florian; Marquet, Adrien; Aranda, Silvia C; Borges, Paulo A V; Dirkse, Gerard; Gabriel, Rosalina; Gonzalez-Mancebo, Juana M; Guisan, Antoine; Muñoz, Jesús; Sim-Sim, Manuela; Vanderpoorten, Alain
2016-07-05
Oceanic islands are of fundamental importance for the conservation of biodiversity because they exhibit high endemism rates coupled with fast extinction rates. Nowhere in Europe is this pattern more conspicuous than in the Macaronesian biogeographic region. A large network of protected areas within the region has been developed, but the question of whether these areas will still be climatically suitable for the globally threatened endemic element in the coming decades remains open. Here, we make predictions on the fate of the Macaronesian endemic bryophyte flora in the context of ongoing climate change. The potential distribution of 35 Macaronesian endemic bryophyte species was assessed under present and future climate conditions using an ensemble modelling approach. Projections of the models under different climate change scenarios predicted an average decrease of suitable areas of 62-87% per species and a significant elevational increase by 2070, so that even the commonest species were predicted to fit either the Vulnerable or Endangered IUCN categories. Complete extinctions were foreseen for six of the studied Macaronesian endemic species. Given the uncertainty regarding the capacity of endemic species to track areas of suitable climate within and outside the islands, active management associated to an effective monitoring program is suggested.
-
Climate threat on the Macaronesian endemic bryophyte flora
Patiño, Jairo; Mateo, Rubén G.; Zanatta, Florian; Marquet, Adrien; Aranda, Silvia C.; Borges, Paulo A. V.; Dirkse, Gerard; Gabriel, Rosalina; Gonzalez-Mancebo, Juana M.; Guisan, Antoine; Muñoz, Jesús; Sim-Sim, Manuela; Vanderpoorten, Alain
2016-01-01
Oceanic islands are of fundamental importance for the conservation of biodiversity because they exhibit high endemism rates coupled with fast extinction rates. Nowhere in Europe is this pattern more conspicuous than in the Macaronesian biogeographic region. A large network of protected areas within the region has been developed, but the question of whether these areas will still be climatically suitable for the globally threatened endemic element in the coming decades remains open. Here, we make predictions on the fate of the Macaronesian endemic bryophyte flora in the context of ongoing climate change. The potential distribution of 35 Macaronesian endemic bryophyte species was assessed under present and future climate conditions using an ensemble modelling approach. Projections of the models under different climate change scenarios predicted an average decrease of suitable areas of 62–87% per species and a significant elevational increase by 2070, so that even the commonest species were predicted to fit either the Vulnerable or Endangered IUCN categories. Complete extinctions were foreseen for six of the studied Macaronesian endemic species. Given the uncertainty regarding the capacity of endemic species to track areas of suitable climate within and outside the islands, active management associated to an effective monitoring program is suggested. PMID:27377592
-
Mascolo, Annamaria; Scavone, Cristina; di Mauro, Gabriella; Grassi, Roberto; Sportiello, Liberata; Cappabianca, Salvatore; Rafaniello, Concetta
2017-01-01
Background and objective The use of contrast media in Italy has exponentially increased in the past 3 decades. However, it is unknown whether there has been an increase in clinical research evaluating the risks associated with contrast media usage, especially regarding contrast-induced nephropathy. To fill this gap in knowledge, we performed a systematic review. Study eligibility criteria Meta-analyses, observational studies, and clinical trials assessing contrast media-induced nephropathy as the safety outcome, in which at least one author was affiliated with an Italian university/health care structure, were eligble. Data sources Ovid MEDLINE, Ovid Embase, Cochrane Methodology Register, and Web of Science were screened. Participants Men and women exposed to contrast media. Results In total, 60 original articles were retrieved with an incremental trend between 1990 and 2017. Cohort studies were the most common study design represented. In total, 45 of 60 (75.0%) studies were monocenter studies and 41 of 60 (68.3%) received no funding. In all, 91.7% of studies disclosed no conflicts of interest and 81.7% had no external collaboration. Most of the studies provided a level of evidence of III-2 (32/60; 53.3%) and II (23/60; 38.3%). In total, 50 of 60 studies (83.3%) were published in a scientific journal ranked in the first quartile of their subject area. Conclusion There was an increased number of studies evaluating contrast-induced nephropathy in Italy during the last three decades. These studies covered procedures to prevent contrast-induced nephropathy or aimed to identify risk factors, biomarkers, and scores, and their related prognosis. PMID:29123405
-
Cortazar, Frank B; Leaf, David E; Owens, Charles T; Laliberte, Karen; Pendergraft, William F; Niles, John L
2017-02-01
Membranous nephropathy is a common cause of the nephrotic syndrome. Treatment with standard regimens fails to induce complete remission in most patients. We evaluated the efficacy of combination therapy with rituximab, low-dose, oral cyclophosphamide, and an accelerated prednisone taper (RCP) for the treatment of idiopathic membranous nephropathy. We analyzed 15 consecutive patients with idiopathic membranous nephropathy treated with RCP at Massachusetts General Hospital. Seven patients (47%) received RCP as initial therapy, and the other eight patients (53%) received RCP for relapsing or refractory disease. All patients had at least 1 year of follow-up. The co-primary outcomes were attainment of partial and complete remission. Partial remission was defined as a urinary protein to creatinine ratio (UPCR) < 3 g/g and a 50% reduction from baseline. Complete remission was defined as a UPCR < 0.3 g/g. Secondary outcomes were serious adverse events and the change in proteinuria, serum creatinine, serum albumin, cholesterol, triglycerides, and immunoglobulin G levels after 1 year of treatment. Over a median follow-up time of 37 (IQR, 34-44) months, 100% of patients achieved partial remission and 93% of patients achieved complete remission at a median time of 2 and 13 months, respectively. After 1 year of treatment, median (IQR) UPCR declined from 8.2 (6.6-11.1) to 0.3 (0.2-0.7) g/g (P < 0.001). Three serious adverse events occurred over 51 patient years. No patients died or progressed to ESKD. Treatment of idiopathic membranous nephropathy with RCP resulted in high rates of complete remission. Larger studies evaluating this regimen are warranted.
-
Everett, Charles J; Thompson, Olivia M; Dismuke, Clara E
2017-03-01
Concentrations of the pesticide DDT (dichlorodiphenyltrichloroethane) and its metabolite DDE (dichlorodiphenyldichloroethylene), in the blood of Mexican Americans, were evaluated to determine their relationships with diabetes and diabetic nephropathy. The data were derived from the National Health and Nutrition Examination Survey (NHANES) 1999-2004 (unweighted N = 1,411, population estimate = 13,760,609). The sample included teens, 12-19 years old, which accounted for 19.8% of the data. The time of the study overlapped the banning of DDT in Mexico in the year 2000, and those participants born in Mexico were exposed to DDT before they immigrated to the US. We sought to better understand the relationship of DDT with diabetes in a race/ethnicity group prone to develop diabetes and exposed to DDT. In this study, nephropathy was defined as urinary albumin to creatinine ratio >30 mg/g, representing microalbuminuria and macroalbuminuria, and total diabetes was defined as diagnosed and undiagnosed diabetes (glycohemoglobin, A1c ≥ 6.5%). The proportion with the isomer p,p'-DDT >0.086 ng/g (above the maximum limit of detection) was 13.3% for Mexican Americans born in the US, and 36.9% for those born in Mexico. Levels of p,p'-DDT >0.086 ng/g were associated with total diabetes with nephropathy (odds ratio = 4.42, 95% CI 2.23-8.76), and with total diabetes without nephropathy (odds ratio = 2.02, 95% CI 1.19-3.44). The third quartile of p,p'-DDE (2.99-7.67 ng/g) and the fourth quartile of p,p'-DDE (≥7.68 ng/g) were associated with diabetic nephropathy and had odds ratios of 5.32 (95% CI 1.05-26.87) and 14.95 (95% CI 2.96-75.48) compared to less than the median, respectively, whereas p,p'-DDE was not associated with total diabetes without nephropathy. The findings of this study differ from those of a prior investigation of the general adult US population in that there were more associations found with the Mexican Americans sample. Published by Elsevier Ltd.
-
[New method for determining endemic levels].
Orellano, Pablo Wenceslao; Reynoso, Julieta Itatí
2011-05-01
Design an instrument for determining endemic levels or ranges using simple calculations; identify and estimate the parameters related to the dynamic transmission of communicable diseases. The parameters for establishing a theoretical curve of expected incidence based on the logistic growth model were identified. The parameters were estimated by nonlinear regression based on the cumulative incidence data from the previous five years. The weekly cumulative incidence of cases of influenza-like illness in Argentina in 2009 was used as an example. It was compared to the 2004-2008 case series in order to determine the cumulative and non-cumulative endemic levels. According to the cumulative endemic levels identified, the country entered the outbreak area in week 2. The data from previous years showed that the maximum expected number of cases or carrying capacity (K) was 1 090 660. When the non-cumulative levels were considered, the outbreak was present in 34 out of 51 weeks. A range of 1.05 to 1.13 was estimated for the basic reproductive rate (R0) in the non-epidemic period from 2004-2008. The new method facilitated the determination of endemic levels using a simple procedure with the identification of parameters that are important for transmission. Although it has limitations such as the fact that the equation used is more appropriate for evaluating diseases with a pronounced annual cycle and less accurate for cycles of less than 1 year, it can be considered a valuable alternative method for determining endemic ranges and a new contribution to the study of epidemic outbreaks at local health surveillance levels.
-
Park, Sungjin; Moon, SeongRyeol; Lee, Kiyoung; Park, Ie Byung; Lee, Dae Ho; Nam, Seungyoon
2018-01-01
Diabetic nephropathy (DN), a major diabetic microvascular complication, has a long and growing list of biomarkers, including microRNA biomarkers, which have not been consistent across preclinical and clinical studies. This meta-analysis aims to identify significant blood- and urine-incident microRNAs as diagnostic/prognostic biomarker candidates for DN. PubMed, Web of Science, and Cochrane Library were searched from their earliest records through 12th Dec 2016. Relevant publications for the meta-analysis included (1) human participants; (2) microRNAs in blood and urine; (3) DN studies; and (4) English language. Four reviewers, including two physicians, independently and blindly extracted published data regarding microRNA profiles in blood and/or urine from subjects with diabetic nephropathy. A random-effect model was used to pool the data. Statistical associations between diabetic nephropathy and urinary or blood microRNA expression levels were assessed. Fourteen out of 327 studies (n=2,747 patients) were selected. Blood or urinary microRNA expression data of diabetic nephropathy were pooled for this analysis. The hsa-miR-126 family was significantly (OR: 0.57; 95% CI: 0.44-0.74; p-value < 0.0001) downregulated in blood from patients with diabetic kidney disease, while its urinary level was upregulated (OR: 2931.12; 95% CI: 9.96-862623.21; p-value = 0.0059). The hsa-miR-770 family microRNA were significantly (OR: 10.24; 95% CI: 2.37-44.25; p-value = 0.0018) upregulated in both blood and urine from patients with diabetic nephropathy. Our meta-analysis suggests that hsa-miR-126 and hsa-miR-770 family microRNA may have important diagnostic and pathogenetic implications for DN, which warrants further systematic clinical studies. © 2018 The Author(s). Published by S. Karger AG, Basel.
-
Leak, T. S.; Perlegas, P.S.; Smith, S.G.; Keene, K.L.; Hicks, P.J.; Langefeld, C.D.; Mychaleckyj, J.C.; Rich, S.S.; Kirk, J.K.; Freedman, B.I.; Bowden, D.W.; Sale, M.M.
2009-01-01
Variants in the engulfment and cell motility 1 (ELMO1) gene are associated with nephropathy due to type 2 diabetes mellitus (T2DM) in a Japanese cohort. We comprehensively evaluated this gene in African American (AA) T2DM patients with end-stage renal disease (ESRD). Three hundred nine HapMap tagging SNPs and 9 reportedly associated SNPs were genotyped in 577 AA T2DM-ESRD patients and 596 AA non-diabetic controls, plus 43 non-diabetic European American controls and 45 Yoruba Nigerian samples for admixture adjustment. Replication analyses were conducted in 558 AAs with T2DM-ESRD and 564 controls without diabetes. Extension analyses included 328 AA with T2DM lacking nephropathy and 326 with non-diabetic ESRD. The original and replication analyses confirmed association with four SNPs in intron 13 (permutation p-values for combined analyses = 0.001-0.003), one in intron 1 (P=0.004) and one in intron 5 (P=0.002) with T2DM-associated ESRD. In a subsequent combined analysis of all 1,135 T2DM-ESRD cases and 1,160 controls, an additional 7 intron 13 SNPs produced evidence of association (P = 3.5×10-5 – P=0.05). No associations were seen with these SNPs in those with T2DM lacking nephropathy or with ESRD due to non-diabetic causes. Variants in intron 13 of the ELMO1 gene appear to confer risk for diabetic nephropathy in AA. PMID:19183347
-
Araki, Shin-ichi; Nishio, Yoshihiko; Araki, Atsushi; Umegaki, Hiroyuki; Sakurai, Takashi; Iimuro, Satoshi; Ohashi, Yasuo; Uzu, Takashi; Maegawa, Hiroshi; Kashiwagi, Atsunori; Ito, Hideki
2012-04-01
Diabetic nephropathy is a serious complication in patients with type 2 diabetes. The aim of this study was to explore the factors associated with the progression of this complication in elderly patients with type 2 diabetes. This retrospective study of a subgroup of patients registered with the Japanese Elderly Diabetes Intervention Trial included 621 Japanese patients with type 2 diabetes mellitus (age ≥ 65 years, 346 with normoalbuminuria, 190 with microalbuminuria and 85 with overt proteinuria). Multivariate Cox proportional hazard regression model with a backward stepwise procedure was applied to select factors with significant effects on worsening of nephropathy stage and the doubling of serum creatinine. During the follow up (median 52 months), 21% of patients progressed from normoalbuminuria and microalbuminuria to a worse nephropathy stage. Aging, female sex and high-density lipoprotein cholesterol were identified as independent and significant factors that worsen nephropathy stage. Also, 6.1% of patients showed doubling of serum creatinine during follow up. A positive history of cardiovascular disease, hyperuricemia and conventional therapy were identified as significant factors involved in the doubling of serum creatinine. The cumulative incidence of the doubling of serum creatinine was significantly lower in the intensive therapy group than the conventional therapy group (P = 0.016), although that of progression of nephropathy stage was similar in the two groups. We identified several factors associated with the progression of diabetic nephropathy in elderly patients with type 2 diabetes. The results suggest that multiple risk factor intervention seems important in preventing deterioration of renal dysfunction. © 2012 Japan Geriatrics Society.
-
A molecular and haematological study of Theileria equi in Balkan donkeys.
Davitkov, Dajana; Davitkov, Darko; Vucicevic, Milos; Stanisic, Ljubodrag; Radakovic, Milena; Glavinic, Uros; Stanimirovic, Zoran
2017-06-01
Equine piroplasmosis in donkeys has been recognised as a serious problem of major economic importance. The present molecular study is the first investigation of the presence of Theileria equi and Babesia caballi in Balkan donkeys and of the possible haematological alterations related to it. A total of 70 apparently healthy donkeys from Serbia were included in this study. The overall prevalence of T. equi infection in donkeys tested with multiplex PCR was 50%. There was no B. caballi-positive sample. Infections in donkeys included in this study seem to be associated with decreased red blood cell count, haemoglobin concentration, haematocrit and platelet count, and with increased white blood cell count, mean corpuscular haemoglobin and mean corpuscular haemoglobin concentration. Altered haematological parameters in donkeys can lead to a decrease in working capacity and production performance. Further molecular research and long-term monitoring of equine piroplasmosis is needed in Serbia and throughout Europe.
-
Rapid assessment of endemic bird areas in Michoacan, Mexico
Gilberto Chavez-Leon; Deborah M. Finch
1999-01-01
Non-sustainable land use practices in the state of Michoacan, Mexico, have perturbed endemic bird h~bitats for several decades. Endemic birds have a restricted geographic and ecological distribution. This feature makes them suitable to be used as indicators of biological diversity and environmental perturbation. Forty-one Mexican endemic species have been recorded in...
-
Yagame, M; Tomino, Y; Miura, M; Tanigaki, T; Suga, T; Nomoto, Y; Sakai, H
1987-01-01
The detection of circulating immune complexes (CIC) in sera from patients with IgA nephropathy is described. A solid-phase anti-C3 Facb enzyme immunoassay (EIA) was employed for detection of IgA-, IgG- and IgM-CIC in sera. The C1q-binding enzyme assay was also used for the detection of CIC in sera from these patients and healthy adults. Twenty-two patients with IgA nephropathy, 14 patients with other glomerular diseases and 19 healthy adults were examined by anti-C3 Facb EIA. The levels of IgA-CIC in sera from patients with IgA nephropathy were significantly higher than those in sera from patients with other glomerular diseases and healthy adults. CIC measured by the C1q-binding enzyme assay was detected in some patients with IgA nephropathy. The levels of serum IgA in patients with IgA nephropathy were significantly higher than those in patients with other glomerular diseases and healthy adults. However, there was no significant correlation between the levels of IgA-CIC in sera and those of serum IgA in patients with IgA nephropathy. There was also no significant correlation between the levels of IgA-CIC in sera and the degree of histopathological injuries in the patients. It is concluded that the solid-phase anti-C3 Facb EIA is useful for the detection of IgA-CIC in sera from patients with IgA nephropathy. PMID:3301093
-
Shaikh, Rozeena; Shahid, Syed M; Mansoor, Qaisar; Ismail, Muhammad; Azhar, Abid
2014-06-01
Diabetes mellitus (DM) has been a growing epidemic worldwide and poses a major socio-economic challenge. The leading cause of DM death is nephropathy due to end-stage renal disease (ESRD). This study aims to identify the possible association of I/D variants of the ACE gene and M268T (rs699) of the AGT gene of renin-angiotensin-aldosterone system (RAAS). Study subjects include 115 patients with DM, 110 with diabetic nephropathy (DN) and 110 controls. Fasting blood samples were collected for biochemical analyses and PCR amplification of specific regions of the ACE and AGT genes using primers. The distribution of ACE (I/D) II 28.8%, ID 35.6% and DD 35.6% while in DN II 24.5%, ID 41% and DD 34.5%. The AGT (M268T) genotypes were distributed in DM as TT 30.4%, MT 66.9% and MM 2.6% while in DN subjects TT 56.4%, MT 42.7% and MM 0.9%. Significant differences were observed in the DD genotype and D allele of the ACE gene and the TT genotype and T allele of AGT genes between diabetic patients with and without nephropathy. The study may conclude that the D allele polymorphism in the ACE gene and the T allele polymorphism in AGT gene may be considered as genetic risk factors for the development of nephropathy in diabetes. © The Author(s) 2014.
-
Gall, M. A.; Hougaard, P.; Borch-Johnsen, K.; Parving, H. H.
1997-01-01
OBJECTIVE: To evaluate putative risk factors for the development of incipient diabetic nephropathy (persistent microalbuminuria) and overt diabetic nephropathy (persistent macroalbuminuria) in patients with non-insulin dependent diabetes. DESIGN: Prospective, observational study of a cohort of white, non-insulin dependent diabetic patients followed for a median period of 5.8 years. SETTING: Outpatient clinic in tertiary referral centre. SUBJECTS: 191 patients aged under 66 years with non-insulin dependent diabetes and normoalbuminuria (urinary albumin excretion rate < 30 mg/24 h) who attended the clinic during 1987. MAIN OUTCOME MEASURES: Incipient and overt diabetic nephropathy. RESULTS: Fifteen patients were lost to follow up. Thirty six of the 176 remaining developed persistent microalbuminuria (30-299 mg/24 h in two out of three consecutive 24 hour urine collections) and five developed persistent macroalbuminuria (> or = mg/24 h in two out of three consecutive collections) during follow up. The five year cumulative incidence of incipient diabetic nephropathy was 23% (95% confidence interval 17% to 30%). Cox's multiple stepwise regression analysis revealed the following risk factors for the development of incipient or overt diabetic nephropathy: increased baseline log urinary albumin excretion rate (relative risk 11.1 (3.4 to 35.9); P < 0.0001); male sex (2.6 (1.2 to 5.4); P < 0.02); presence of retinopathy (2.4 (1.3 to 4.7); P < 0.01); increased serum cholesterol concentration (1.4 (1.1 to 1.7); P < 0.01); haemoglobin A1c concentration (1.2 (1.0 to 1.4); P < 0.05); and age (1.07 (1.02 to 1.12); P < 0.01). Known duration of diabetes, body mass index, arterial blood pressure, serum creatinine concentration, pre-existing coronary heart disease, and history of smoking were not risk factors. CONCLUSION: Several potentially modifiable risk factors predict the development of incipient and overt diabetic nephropathy in normoalbuminuric patients with non
-
Amini, Sabrieh; Javanmardi, Mitra; Mokarizadeh, Aram; Maroofi, Farzad; Jalali, Chiya; Azadi, Namam-Ali; Mohammadi, Hamid; Abdi, Mohammad
2016-06-01
Given the growing rate of patients with type 2 diabetes mellitus, uncovering the effects of gene polymorphism on diabetes pathogenesis has attracted a lot of attention. Because glucose transporter 1 is involved in glucose uptake, the polymorphism of this gene may be an important risk factor in type 2 diabetes mellitus or in the progression of diabetes complications such as diabetic nephropathy. As far as the authors are concerned, this study is the first one aiming at evaluating the probable effects of solute carrier family 2 facilitated glucose transporter member 1 (SLC2A1) HaeIII polymorphism on clinical and laboratory outcomes of Kurdish patients with type 2 diabetes mellitus. This study was conducted involving 126 diabetic nephropathy patients and 150 diabetic patients without renal involvement. Serum levels of Cystatin C, fasting blood glucose, creatinine and urinary albumin; levels of glycated hemoglobin and estimated glomerular filtration rate were measured. Moreover, the Hae III polymorphism of SLC2A1 gene was determined by PCR-restriction fragment length polymorphism (RFLP). The rate of CC genotype was higher (37%) in patients with diabetic nephropathy compared with controls. There were a significant correlation between the CC genotype and risk of diabetic nephropathy. There were significant correlations between genotypes, serum Cystatin C and estimated glomerular filtration rate in patients with diabetic nephropathy. The results demonstrated the high frequency of C allele of SLC2A1 HaeIII in Kurdish patients with diabetic nephropathy. It was also found that this polymorphism is a significant risk factor for diabetic nephropathy. The effect of this polymorphism on clinical and laboratory characteristics of diabetic nephropathy patients was significant. © The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
-
2007-06-01
Washington headquarters Services , Directorate for Information Operations and Reports, 1215 Jefferson Davis Highway, Suite 1204, Arlington, VA 22202-4302...1999); Laura Silber and Alan Little, Yugoslavia: Death of a Nation (New York: TV Books, 1996); Susan L. Woodward, Balkan Tragedy: Chaos and...community. See Biermann, Lehrjahre im Kosovo: Das Scheitern der internationalen Krisenprävention vor Kriegsausbruch, 314-319. 69 Silber and Little, 25
-
Vertebrate endemism in south-eastern Africa numerically redefines a biodiversity hotspot.
Perera, Sandun J; ProcheŞ, Şerban; Ratnayake-Perera, Dayani; Ramdhani, Syd
2018-02-20
We use numerical methods to explore patterns of vertebrate endemism in south-eastern Africa, refining the boundaries of the intuitively-defined Maputaland-Pondoland-Albany biodiversity hotspot, also proposing a zoogeographic regionalisation. An incidence matrix of 300 vertebrate species endemic to south-eastern Africa sensu lato in 37 operational geographic units were used in (a) phenetic cluster analysis (PCA) using the algorithm of unweighted pair-group method with arithmetic averages (phenetic approach), and (b) parsimony analysis of endemicity (PAE; parsimony approach), in order to numerically evaluate the bioregional delimitations. The analyses provide a valid biogeographical entity 37% larger than the Maputaland-Pondoland-Albany hotspot, but substantially (131%) higher in vertebrate endemicity viz. the Greater Maputaland-Pondoland-Albany (GMPA) region of vertebrate endemism. South-east Africa is recognised as a dominion in the global zoogeographical area hierarchy, with subordinate units including the GMPA province. Various spatially-based measures of endemism were mapped for vertebrate species restricted to the dominion, i.e. endemic to south-eastern Africa sensu stricto. Areas and centres of endemism detected respectively from PAE and PCA, within the south-east Africa dominion also support the refined boundary of the GMPA region of endemism, which provides a better spatial conservation priority compared to the Maputaland-Pondoland-Albany hotspot. Reptiles and amphibians are found to be the main drivers of the overall pattern of endemism, while the pattern in freshwater fish is the most distinctive. Our analyses also indicate a good congruence of the centres of endemism across different terrestrial vertebrate taxa.
-
Khidr, Emad Gamil; Ali, Shawkey Saddik; Elshafey, Mostafa Mahmoud; Fawzy, Olfat Ahmed
2017-08-30
Diabetes mellitus is a fast-growing health problem in Egypt affecting morbidity, mortality and health care resources. Irisin, a new exercise-induced myokine inducing browning of white adipose tissues, has gained a great interest as a potential new target for combating type 2 diabetes mellitus (T2DM) and its complications. In this study, we assessed serum irisin levels in T2DM and diabetic nephropathy to elucidate possible relationships between irisin and metabolic parameters and renal functions. We also investigated, for the first time in Egypt, the association of FNDC5 rs16835198 G>T polymorphism with T2DM, diabetic nephropathy and irisin levels. One hundred type 2 diabetic patients (40 normoalbuminuric and 60 with nephropathy) as well as fifty control subjects were enrolled in this study. Serum irisin and insulin were evaluated by ELISA. Genomic DNA was genotyped for FNDC5 rs16835198 polymorphism using TaqMan genotyping assay. Serum irisin levels were lower in diabetic patients compared to controls and this decrease was more pronounced in diabetic nephropathy. Irisin correlates with metabolic parameters and renal functions. Frequencies of T allele and TT genotype were significantly lower among T2DM and diabetic nephropathy patients compared to controls. Moreover, G allele was associated with elevated insulin resistance and dyslipidemia without effect on circulating irisin levels. T2DM and diabetic nephropathy are associated with decreased levels of irisin. FNDC5 rs16835198 TT genotype associates with decreased risk of T2DM in Egyptians with no effect on renal complications. Also, G allele has insulin desensitizing action with no association with circulating irisin levels. Copyright © 2017 Elsevier B.V. All rights reserved.
-
Reducing the Risks for Contrast-Induced Nephropathy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stacul, Fulvio
2005-12-15
Contrast-induced nephropathy (CIN) is one of the most serious adverse events associated with the use of contrast media (CM). Patients who develop this complication can have increased morbidity, higher rates of mortality, lengthy hospital stays, and poor long-term outcomes. Although CIN cannot be eliminated, the chances of developing this condition can be reduced by using appropriate prevention strategies. An important first step to reduce the chance of CIN is to identify risk factors associated with this condition. Patients with a previously elevated serum creatinine level, especially when secondary to diabetic nephropathy, are at great risk for developing CIN. Other patient-relatedmore » risk factors include concurrent use of nephrotoxic medications, dehydration, congestive heart failure, age greater than 70 years, and probably the presence of diabetes mellitus even if serum creatinine is normal. Adequate hydration is widely accepted as an important prophylactic measure for preventing CIN, but the optimal hydration regimen is still debatable. The risk of CIN increases with greater doses of CM, as well as with the type of CM used. A high-osmolar CM poses a greater risk of CIN than does a low-osmolar CM and, as recent but limited data suggest, the use of an iso-osmolar CM is less nephrotoxic than a low-osmolar CM in patients with renal impairment following intra-arterial procedures, although this finding needs to be verified in future clinical studies. Pharmacologic agents such as calcium channel blockers, dopamine, atrial natriuretic peptide, fenoldopam, prostaglandin E1, and endothelin receptor antagonist have not been proven effective against CIN development. Controversies still exist on the possible effectiveness of theophylline and N-acetylcysteine. Simple strategies for the prevention of CIN in at-risk patients are reviewed and unproven interventions are discussed.« less
-
Hameed, Iqra; Masoodi, Shariq R; Malik, Perveez A; Mir, Shahnaz A; Ghazanfar, Khalid; Ganai, Bashir A
2018-06-30
Diabetic nephropathy is the single strongest predictor of mortality in patients with diabetes. The development of overt nephropathy involves important inter-individual variations, even after adjusting for potential confounding influences of modifiable and non-modifiable risk factors. Genome-wide transcriptome studies have reported the activation of inflammatory signaling pathways and there is mounting indication of the role of genetic factors. We screened nine genetic variations in three cytokine genes (TNF-α, IL-6 and IL-β) in 1326 unrelated subjects comprising of healthy controls (n = 464), type 2 diabetics with nephropathy (DN, n = 448) and type 2 diabetes without nephropathy (T2D, n = 414) by sequence-specific amplification. Functional implication of SNPs was elucidated by correlation studies and relative gene expression using Realtime-Quantitative PCR (RT-qPCR). Individual SNP analysis showed highest association of IL-1β rs16944-TT genotype (OR = 3.51, 95%CI = 2.36-5.21, P = 0.001) and TNF-α rs1800629-AA genotype (OR = 2.75, 95% CI = 1.64-4.59, P = 0.001) with T2D and DN respectively. The haplotype frequency showed significant risk of seven combinations among T2D and four combinations among DN subjects. The highest risk of T2D and DN was associated with GGTGAGTTT (OR = 4.25, 95%CI = 3.3-14.20, P = 0.0016) and GACGACCTT (OR = 21.3, 95%CI = 15.1-28.33, P = 0.026) haplotypes respectively. Relative expression by RT-qPCR showed increased cytokine expression in cases as compared to controls. TNF-α expression was increased by more than four-folds (n-fold = 4.43 ± 1.11) in DN. TNF-α, IL-6 and IL-1β transcript levels were significantly modulated by promoter region SNPs. The present study implicates a strong association between cytokine TNF-α, IL-6 and IL-1β gene promoter polymorphisms and modulation of transcript levels with susceptibility to nephropathy in diabetes subjects. Copyright
-
Weisrock, Fabian; Fritschka, Max; Beckmann, Sebastian; Litmeier, Simon; Wagner, Josephine; Tahirovic, Elvis; Radenovic, Sara; Zelenak, Christine; Hashemi, Djawid; Busjahn, Andreas; Krahn, Thomas; Pieske, Burkert; Dinh, Wilfried; Düngen, Hans-Dirk
2017-08-01
Endothelial dysfunction plays a major role in cardiovascular diseases and pulse amplitude tonometry (PAT) offers a non-invasive way to assess endothelial dysfunction. However, data about the reliability of PAT in cardiovascular patient populations are scarce. Thus, we evaluated the test-retest reliability of PAT using the natural logarithmic transformed reactive hyperaemia index (LnRHI). Our cohort consisted of 91 patients (mean age: 65±9.7 years, 32% female), who were divided into four groups: those with heart failure with preserved ejection fraction (HFpEF) ( n=25), heart failure with reduced ejection fraction (HFrEF) ( n=22), diabetic nephropathy ( n=21), and arterial hypertension ( n=23). All subjects underwent two separate PAT measurements at a median interval of 7 days (range 4-14 days). LnRHI derived by PAT showed good reliability in subjects with diabetic nephropathy (intra-class correlation (ICC) = 0.863) and satisfactory reliability in patients with both HFpEF (ICC = 0.557) and HFrEF (ICC = 0.576). However, in subjects with arterial hypertension, reliability was poor (ICC = 0.125). We demonstrated that PAT is a reliable technique to assess endothelial dysfunction in adults with diabetic nephropathy, HFpEF or HFrEF. However, in subjects with arterial hypertension, we did not find sufficient reliability, which can possibly be attributed to variations in heart rate and the respective time of the assessments. Clinical Trial Registration Identifier: NCT02299960.
-
Moreso, F; Lopez, M; Vallejos, A; Giordani, C; Riera, L; Fulladosa, X; Hueso, M; Alsina, J; Grinyó, J M; Serón, D
2001-05-01
To evaluate the utility of intimal thickness and interstitial width as a primary efficacy variable in the design of clinical trials aimed to modify the natural history of chronic allograft nephropathy. A donor and a 4-month protocol biopsy were evaluated in 40 stable grafts according to the Banff schema. In 27 patients, a second protocol biopsy was done at 1 yr. Arterial intimal volume fraction (Vvintima/artery) and cortical interstitial volume fraction (Vvinterstitium/cortex) were estimated with a point counting technique. Chronic Banff scores increased during follow-up, while acute scores reached its peak at 4 months. Vvintima/artery and Vvinterstitium/cortex significantly increased at 4 months, but not at 1 yr. Vvintima/artery at 4 months correlated with donor Vvintima/artery (r = 0.57, p < 0.001), histocompatibility (r = 0.38, p = 0.01) and serum cholesterol (r = 0.31, p = 0.047). Vvinterstitium/cortex at 4 months correlated with recipient body surface area (r = 0.44, p = 0.004) and delayed graft function (p = 0.016). Power calculations showed that Vvintima/artery and Vvinterstitium/cortex allow an important reduction in minimum sample size of a hypothetical trial aimed to prevent chronic allograft nephropathy. Intimal thickening and interstitial widening progresses rapidly during the first 4 months after transplantation and slowly thereafter. These parameters can be considered as a primary efficacy variable in trials aimed to prevent chronic allograft nephropathy.
-
Arık, Hasan Onur; Yalcin, Arzu Didem; Gumuslu, Saadet; Genç, Gizem Esra; Turan, Adil; Sanlioglu, Ahter Dilsad
2013-01-01
Background Hyperglycemia is among the potent factors that may induce or facilitate apoptosis. TNF-Related Apoptosis-Inducing Factor (TRAIL) is known for its apoptotic and immunomodulatory effects that have recently been correlated with diabetes. We examined serum-soluble TRAIL (sTRAIL) and high-sensitivity CRP (hs-CRP) levels and their association with various distinct parameters in type 2 diabetic nephropathy patients with diabetic foot disease. Material/Methods Twenty-two diabetic nephropathy patients with foot ulcers were enrolled in our study. Patients had been diagnosed with diabetes at age 24±10.58 years. Circulating sTRAIL and Hs-CRP levels were compared with control values, and possible correlations were investigated with parameters such as age, Wagner’s Grade (WG), BMI, HbA1c, and creatinine. Results Serum sTRAIL levels were significantly reduced in the patient group, compared to healthy subjects. High HsCRP levels correlated with age, and WGS correlated with BMI and creatinine levels. Conclusions Significantly suppressed sTRAIL levels in diabetic nephropathy patients with foot ulcers compared to healthy controls suggest a protective role for TRAIL in the disease setting. PMID:23986130
-
Severe Diabetic Nephropathy in Type 1 Diabetes and Pregnancy - A Case Series
Piccoli, Giorgina B.; Tavassoli, Elisabetta; Melluzza, Carmela; Grassi, Giorgio; Monzeglio, Clara; Donvito, Valentina; Leone, Filomena; Attini, Rossella; Ghiotto, Sara; Clari, Roberta; Moro, Irene; Fassio, Federica; Parisi, Silvia; Pilloni, Eleonora; Vigotti, Federica N.; Giuffrida, Domenica; Rolfo, Alessandro; Todros, Tullia
2013-01-01
BACKGROUND: Diabetes and nephropathy are important challenges during pregnancy, increasingly encountered because of the advances in maternal-fetal care. AIM: To evaluate the maternal and fetal outcomes recorded in "severe" diabetic nephropathy in type 1 diabetic patients referred to nephrological healtcare. METHODS: The study was performed in an outpatient unit dedicated to kidney diseases in pregnancy (with joint nephrological and obstetric follow-up and strict cooperation with the diabetes unit). 383 pregnancies were referred to the outpatient unit in 2000-2012, 14 of which were complicated by type 1 diabetes. The report includes 12 deliveries, including 2 pregnancies in 1 patient; one twin pregnancy; 2 spontaneous abortions were not included. All cases had long-standing type 1 diabetes (median of 21 (15-31) years), relatively high median age (35 (29-40) years) and end-organ damage (all patients presented laser-treated retinopathy and half of them clinical neuropathy). Median glomerular filtration rate (GFR) at referral was 67 ml/min (48-122.6), proteinuria was 1.6 g/day (0.1-6.3 g/day). RESULTS: Proteinuria steeply increased in 11/12 patients, reaching the nephrotic range in nine (6 above 5 g/day). One patient increased by 2 chronic kidney disease (CKD) stages. Support therapy included blood pressure and diabetes control, bed rest, and moderate protein restriction. All children were preterm (7 early preterm); early spontaneous labor occurred in 4/12 patients. All singletons were appropriate for gestational age and developed normally after birth. The male twin child died 6 days after birth (after surgery for great vessel transposition). CONCLUSIONS: Diabetic patients with severe diabetic nephropathy are still present a considerable challenge. Therefore, further investigations are required, particularly on proteinuria management and the occurrence of spontaneous labor. PMID:24172700
-
Song, QuanQuan; Liu, Yun Qi; Sun, Li Yan; Deng, Qing; Wang, Shao Ping; Cao, Yan Hong; Zhang, Xue Ying; Jiang, Yuan Yuan; Lv, Hong Yan; Duan, Li Bin; Yu, Jun
2018-01-01
Osteoarthritis (OA) is a considerable health problem worldwide, and the prevalence of OA varies in different regions. In this study, the prevalence of OA in Kashin-Beck disease (KBD) and non-KBD endemic areas was examined, respectively. According to monitoring data, 4 types of regions (including none, mild, moderate and high KBD endemic areas) in Heilongjiang and Jilin provinces were selected. All local residents were eligible for inclusion criteria have undergone X-ray images of hands and anteroposterior image of knees. A total of 1673 cases were collected, 1446 cases were analyzed after removing the KBD patients (227). The overall hand OA and knee OA detection rates were 33.3% (481/1446) and 56.6% (818/1446), respectively. After being standardized by age, the detection rate of hand OA in the KBD endemic areas was significantly higher than that in the non-endemic endemic areas. Differently, there was no significant difference in the detection rates of knee OA between the KBD endemic areas and the non-endemic area. The correlation coefficient between the severity of OA and the severity of knee OA was 0.358 and 0.197 in the KBD and non-KBD endemic areas, respectively. Where the KBD historical prevalence level was higher, the severity of the residents’ hand OA was more serious. The detection rates of hand OA and knee OA increased with age. The detection rate of knee OA increased with the increase in body mass index. The prevalence of hand OA was closely related to the pathogenic factors of Kashin-Beck disease, and the prevalence of knee OA had no significant correlation with KBD pathogenic factors. PMID:29320581
-
Comparison of dual RAAS blockade and higher-dose RAAS inhibition on nephropathy progression.
Bakris, George L; Weir, Matthew R
2008-04-01
Although the risk of dying from cardiovascular disease (CVD) is greater than for progressing to end-stage renal disease (ESRD), the increasing prevalence of diabetes mellitus and reduced mortality from CVD have contributed to an increased incidence of ESRD. Use of renin-angiotensin-aldosterone system (RAAS) blockers to reduce blood pressure is proven to reduce the rate of nephropathy progression. Theoretically, more complete RAAS inhibition may enhance the ability to slow nephropathy progression. Combining an angiotensin-converting enzyme inhibitor (ACEI) and an angiotensin receptor blocker (ARB) more completely inhibits the RAAS, potentially providing greater opportunity for renoprotection. Proteinuria is a strong independent predictor of poor renal and cardiovascular outcomes. Therefore, targeting interventions that further reduce proteinuria may yield better outcomes. This review presents evidence supporting the hypothesis that higher doses of RAAS inhibition or dual RAAS blockade are more effective in reducing proteinuria. Clinical data and ongoing trials will be discussed in the context of this hypothesis.
-
Wt-1 Expression Linked to Nitric Oxide Availability during Neonatal Obstructive Nephropathy
Mazzei, Luciana; Manucha, Walter
2013-01-01
The wt-1 gene encodes a zinc finger DNA-binding protein that acts as a transcriptional activator or repressor depending on the cellular or chromosomal context. The wt-1 regulates the expression of a large number of genes that have a critical role in kidney development. Congenital obstructive nephropathy disrupts normal renal development and causes chronic progressive interstitial fibrosis, which contributes to renal growth arrest, ultimately leading to chronic renal failure. Wt-1 is downregulated during congenital obstructive nephropathy, leading to apoptosis. Of great interest, nitric oxide bioavailability associated with heat shock protein 70 (Hsp70) interaction may modulate wt-1 mRNA expression, preventing obstruction-induced cell death during neonatal unilateral ureteral obstruction. Moreover, recent genetic researches have allowed characterization of many of the complex interactions among the individual components cited, but the realization of new biochemical, molecular, and functional experiments as proposed in our and other research labs allows us to establish a deeper level of commitment among proteins involved and the potential pathogenic consequences of their imbalance. PMID:24288526
-
Vallianou, N; Stratigou, T; Paikopoulou, A; Apostolou, T; Vlassopoulou, B; Tsagarakis, S; Ioannidis, G
2018-04-13
The purpose of this study was to evaluate the outcome of DM2 patients with nephropathy when they are under surveillance of a joined clinic run by endocrinologists & nephrologists. A cohort of 106 patients with DM2, 42-83 years of age, and eGFR < 60 ml/min/m 2 were included. Age, sex, duration of diabetes, duration of attending our clinic, smoking habits, BMI, data regarding ischemic heart disease and induction of hemodialysis, urine albumin excretion (UAE) levels, eGFR (MDRD equation) and values of various biochemical parameters were recorded too. Follow-up period ranged from one to 25 years. Paired samples t-test and non-parametrical Kruskal-Wallis test were used for the analyses of the data. Fifty percent of patients had no further progression, 25.9% improvement, while 24.1% had worsening of the UAE levels. During the follow-up in the joined clinic, there was a smaller than the expected from the medical literature decrease in median eGFR, i.e. 2,3 ml/min/m 2 and a statistically significant improvement in glycosylated hemoglobin levels from 8.0% to 7.4% (p = 0.016). Time in years of follow-up in the joined clinic of our hospital appeared to be the most significant factor in the improvement or stabilization against deterioration of the UAE levels (p = 0.018). Close follow-up of DM2 patients with eGFR < 60 ml/min/m 2 has resulted in a minor annual eGFR decrease. Monitoring of these patients in a specialized diabetic nephropathy clinic is beneficial for this group of patients for delaying the occurrence of end-stage renal disease. Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.
-
Oyabu, Chikako; Ushigome, Emi; Matsumoto, Shinobu; Tanaka, Toru; Hasegawa, Goji; Nakamura, Naoto; Ohnishi, Masayoshi; Tsunoda, Sei; Ushigome, Hidetaka; Yokota, Isao; Tanaka, Muhei; Asano, Mai; Yamazaki, Masahiro; Fukui, Michiaki
2017-11-01
Maximum home systolic blood pressure has been shown to predict target organ damage. We aimed to clarify the association between maximum home systolic blood pressure and urine albumin to creatinine ratio, an indicator of early-phase diabetic nephropathy in patients with type 2 diabetes. In 1040 patients, we assessed the relationship of mean or maximum home systolic blood pressure and urine albumin to creatinine ratio, and compared the area under the receiver operating characteristic curve of mean or maximum home systolic blood pressure for diabetic nephropathy (urine albumin to creatinine ratio ⩾30 mg/g Cr). Multivariate linear regression analyses indicated that mean morning systolic blood pressure ( β = 0.010, p < 0.001) and maximum morning systolic blood pressure ( β = 0.008, p < 0.001) were significantly associated with urine albumin to creatinine ratio. Area under the receiver operating characteristic curve (95% confidence interval) for diabetic nephropathy in mean and maximum morning systolic blood pressure was 0.667 (0.634-0.700; p < 0.001) and 0.671 (0.638-0.703; p < 0.001), respectively. Maximum home systolic blood pressure, as well as mean home systolic blood pressure, was significantly associated with diabetic nephropathy in patients with type 2 diabetes.
-
Liu, Xu-Lin; Liu, Wen-Ping; Wang, Li-Li; Feng, Liang
2018-06-01
Diabetic nephropathy (DN) is closely related to immune-mediated inflammatory damage. Pyrrosiae folium is used commonly for the urinary system diseases with a good efficacy, which contains abundant flavonoids (SWHT). This study was performed to investigate the therapeutic effect of SWHT on DN and its effect on inflammatory response. In this study, the main active components of SWHT were identified by high performance liquid chromatography (HPLC). The results showed that SWHT mainly contained mangiferin and isomucoside. Rat model of diabetic nephropathy (DN) was established by feeding high glucose & high fat diet and injecting streptozocin (STZ). Then the rats were randomly divided into control group, DN model group, positive control group, and SWHT groups (50, 100, 200 mg·kg⁻¹, ig). The levels of AGEs and RAGE in serum were measured by ELISA after 12 weeks of drug administration. The serum creatinine, blood urea nitrogen and total protein levels were detected by using test kit. HE staining and transmission electron microscopy were applied to observe the pathological changes and structure of renal tissue. Western blot and ELISA were used to detect the protein expression and content levels of interleukin 6 (IL-6), tumor necrosis factor (TNF-α) and IL-1β in renal tissue. Results showed that SWHT significantly decreased serum AGEs and RAGE levels in DN rats; decreased serum creatinine, blood urea nitrogen and total urinary protein levels, improved renal pathological damages and reduced basement membrane thickening in DN rats. In addition, SWHT down-regulated the protein expression levels of inflammatory mediators IL-6, TNF-α and IL-1β. The research studies indicated that SWHT component had a potential anti-diabetic nephropathy activity, and its improvement effect on pathological damages may be related to reducing inflammation. This provides the basis for the scientific and rational application of P. folium, and also provides active components for further
-
Yajima, A; Gabrielli, A F; Montresor, A; Engels, D
2011-02-01
The authors conducted a systematic literature review with the following aims: to investigate how frequently soil-transmitted helminthiasis (STH) infections are endemic where schistosomiasis is present; and to assess the correlation between the risk level of schistosomiasis and that of STH. Among 155 sites on which data were collected and analyzed, schistosomiasis was present in 130, all of which were also co-endemic for STH, whereas 25 sites were endemic only for STH. Ninety percent (117 out of 130) of the areas eligible for preventive chemotherapy (PC) against schistosomiasis are also eligible for PC against STH. This fact provides managers of control programmes with the operationally important indication that use of available information on endemicity of schistosomiasis is a valid tool to predict the presence of STH in the same geographical area and to estimate the need of PC for STH. The implementation of this tool is expected to save financial and human resources and help accelerate the scale-up of PC throughout the world. Copyright © 2010 Royal Society of Tropical Medicine and Hygiene. Published by Elsevier Ltd. All rights reserved.
-
NASA Astrophysics Data System (ADS)
Georgiou, E.; Karachaliou, E.; Stylianidis, E.
2017-08-01
Characteristic example of the Balkan architecture of the 19th century, consists the "Tower house" which is found in the region of Epirus and Western Macedonia, Greece. Nowadays, the only information about these heritage buildings could be abstracted by the architectural designs on hand and the model - Tower that is being displayed in the Folklore Museum of the Municipality of Kozani, Greece, as a maquette. The current work generates a scaled 3D digital model of the "Tower house", by using photogrammetry techniques applied on the model-maquette that is being displayed in the Museum exhibits.
-
An annotated checklist of the Greek Stonefly Fauna (Insecta: Plecoptera).
Karaouzas, Ioannis; Andriopoulou, Argyro; Kouvarda, Theodora; Murányi, Dávid
2016-05-17
An overview of the Greek stonefly (Plecoptera) fauna is presented as an annotated index of all available published records. These records have resulted in an updated species list reflecting current taxonomy and species distributions of the Greek peninsula and islands. Currently, a total of 71 species and seven subspecies belonging to seven families and 19 genera are reported from Greece. There is high species endemicity of the Leuctridae and Nemouridae, particularly on the Greek islands. The endemics known from Greece comprise thirty species representing 42% of the Greek stonefly fauna. The remaining taxa are typical Balkan and Mediterranean species.
-
Dahanukar, Neelesh; Krutha, Keerthi; Paingankar, Mandar S.; Padhye, Anand D.; Modak, Nikhil; Molur, Sanjay
2013-01-01
The Western Ghats of India harbors a rich diversity of amphibians with more than 77% species endemic to this region. At least 42% of the endemic species are threatened due to several anthropogenic stressors. However, information on amphibian diseases and their impacts on amphibian populations in this region are scarce. We report the occurrence of Batrachochytridium dendrobatidis (Bd), an epidermal aquatic fungal pathogen that causes chytridiomycosis in amphibians, from the Western Ghats. In the current study we detected the occurrence of a native Asian Bd strain from three endemic and threatened species of anurans, Bombay Night Frog Nyctibatrachus humayuni, Leith's Leaping Frog Indirana leithii and Bombay Bubble Nest Frog Raorchestes bombayensis, for the first time from the northern Western Ghats of India based on diagnostic nested PCR, quantitative PCR, DNA sequencing and histopathology. While, the Bd infected I. leithii and R. bombayensis did not show any external symptoms, N. humayuni showed lesions on the skin, browning of skin and sloughing. Sequencing of Bd 5.8S ribosomal RNA gene, and the ITS1 and ITS2 regions, revealed that the current Bd strain is related to a haplotype endemic to Asia. Our findings confirm the presence of Bd in northern Western Ghats and the affected amphibians may or may not show detectable clinical symptoms. We suggest that the significance of diseases as potential threat to amphibian populations of the Western Ghats needs to be highlighted from the conservation point of view. PMID:24147018
-
A prospective, randomized therapeutic trial for schistosomal specific nephropathy.
Sobh, M A; Moustafa, F E; Sally, S M; Foda, M A; Deelder, A M; Ghoneim, M A
1989-11-01
In this work 26 patients with schistosomal specific nephropathy were randomly distributed among three groups. Group I cases were given anti-schistosomal drugs (oxamniquine and praziquantel), group II cases were given anti-schistosomal drugs plus prednisolone, and group III cases were given anti-schistosomal drugs plus cyclosporine. The schistosomal specificity of kidney lesions was assessed by detecting the schistosomal specific antigens (CAA and CCA) and antibodies deposited in the renal glomeruli of these patients. Patients who had another etiologic cause which may explain their kidney disease were not admitted to this study. After initiation of the treatment, patients were followed up every other week in the outpatient clinic for 12 months. Follow-up showed complete remission of proteinuria in two cases in group II (duration of remission was 4 and 8 months) and in one case in group III (duration of remission was 6 months) but in none in group I. Partial remission was observed in one case in group I, in three cases in group II and in one case in group III. During the observation period, improvement in kidney function was observed in two cases in group II but deterioration in kidney function was observed in one case in group I and in one other case in group III. We conclude that in patients with schistosomal nephropathy, none of the tried therapeutic regimens produce regression of the disease if given to patients with established disease.
-
Low-protein diet for diabetic nephropathy: a meta-analysis of randomized controlled trials.
Pan, Yu; Guo, Li Li; Jin, Hui Min
2008-09-01
A low-protein diet (LPD) has been proposed for many years to delay the progression of diabetic nephropathy. However, the efficacy of an LPD with respect to renal outcome is disputed. We aimed to determine the effect of an LPD on renal function in patients with type 1 or 2 diabetic renal diseases by using a meta-analysis of randomized controlled trials. Medline, EMBASE, and the Cochrane Central Register of Controlled Trials were searched. Eight studies met the inclusion criteria for our meta-analysis: a duration of >6 mo, use of a randomized control group, availability of outcome data for changes in glomerular filtration rate (GFR) or creatinine clearance rate (CCR), and albuminuria or proteinuria in patients with type 1 or 2 diabetic nephropathy. Data were combined by means of a fixed-effects model. Weighted mean differences (WMD) were calculated for the change in GFR or CCR, glycated hemoglobin (HbA(1c)), and serum albumin between the LPD and control groups. A random-effects model was also used to calculate the standardized mean difference for the change in urinary albumin excretion or proteinuria. Overall, a change in WMD for GFR or CCR was not significantly associated with an LPD, but a decrease in WMD for HbA(1c) was significant in the LPD group (P = 0.005). Although the benefit of LPD therapy on proteinuria was significant (P = 0.003), great heterogeneity was observed. In a subgroup analysis, LPD resulted in lower serum albumin concentrations. LPD was not associated with a significant improvement of renal function in patients with either types 1 or 2 diabetic nephropathy.
-
Sulforaphane, a natural constituent of broccoli, prevents cell death and inflammation in nephropathy
Guerrero-Beltrán, Carlos Enrique; Mukhopadhyay, Partha; Horváth, Béla; Rajesh, Mohanraj; Tapia, Edilia; García-Torres, Itzhel; Pedraza-Chaverri, José; Pacher, Pál
2011-01-01
Cisplatin (cis-diamminedichloroplatinum II, CIS) is a potent and widely used chemotherapeutic agent to treat various malignancies, but its therapeutic use is limited because of the dose-dependent nephrotoxicity. Cell death and inflammation play key role in the development and progression of CIS-induced nephropathy. Sulforaphane (SFN), a natural constituent of cruciferous vegetables such as broccoli, Brussels sprouts, etc., has been shown to exert various protective effects in models of tissue injury and cancer. In this study, we have investigated the role of pro-survival, cell death and inflammatory signaling pathways using a rodent model of CIS-induced nephropathy, and explored the effects of SFN on these processes. Cisplatin triggered marked activation of stress signaling pathways (p53, Jun N-terminal kinase (JNK), and p38-α MAPK) and promoted cell death in the kidneys (increased DNA fragmentation, caspases-3/7 activity, TUNEL), associated with attenuation of various pro-survival signaling pathways (e.g. extracellular signal-regulated kinase (ERK) and p38-β MAPK). Cisplatin also markedly enhanced inflammation in the kidneys (promoted NF-κB activation, increased expression of adhesion molecules ICAM and VCAM, enhanced tumor necrosis factor-alpha (TNF-α) levels, and inflammatory cell infiltration). These effects were significantly attenuated by pre-treatment of rodents with SFN. Cisplatin-induced nephropathy is associated with activation of various cell death and pro-inflammatory pathways (p53, JNK, p38-α, TNF-α, and NF-κB) and impairments of key pro-survival signaling mechanisms (ERK and p38-β). SFN is able to prevent the CIS-induced renal injury by modulating these pathways, providing a novel approach for preventing this devastating complication of the chemotherapy. PMID:21684138
-
Marchant, Vanessa; Droguett, Alejandra; Valderrama, Graciela; Burgos, M Eugenia; Carpio, Daniel; Kerr, Bredford; Ruiz-Ortega, Marta; Egido, Jesús; Mezzano, Sergio
2015-09-15
Diabetic nephropathy (DN) is currently a leading cause of end-stage renal failure worldwide. Gremlin was identified as a gene differentially expressed in mesangial cells exposed to high glucose and in experimental diabetic kidneys. We have described that Gremlin is highly expressed in biopsies from patients with diabetic nephropathy, predominantly in areas of tubulointerstitial fibrosis. In streptozotocin (STZ)-induced experimental diabetes, Gremlin deletion using Grem1 heterozygous knockout mice or by gene silencing, ameliorates renal damage. To study the in vivo role of Gremlin in renal damage, we developed a diabetic model induced by STZ in transgenic (TG) mice expressing human Gremlin in proximal tubular epithelial cells. The albuminuria/creatinuria ratio, determined at week 20 after treatment, was significantly increased in diabetic mice but with no significant differences between transgenic (TG/STZ) and wild-type mice (WT/STZ). To assess the level of renal damage, kidney tissue was analyzed by light microscopy (periodic acid-Schiff and Masson staining), electron microscopy, and quantitative PCR. TG/STZ mice had significantly greater thickening of the glomerular basement membrane, increased mesangial matrix, and podocytopenia vs. WT/STZ. At the tubulointerstitial level, TG/STZ showed increased cell infiltration and mild interstitial fibrosis. In addition, we observed a decreased expression of podocin and overexpression of monocyte chemoattractant protein-1 and fibrotic-related markers, including transforming growth factor-β1, Col1a1, and α-smooth muscle actin. Together, these results show that TG mice overexpressing Gremlin in renal tubules develop greater glomerular and tubulointerstitial injury in response to diabetic-mediated damage and support the involvement of Gremlin in diabetic nephropathy. Copyright © 2015 the American Physiological Society.
-
Cysticerci-related single parenchymal brain enhancing lesions in non-endemic countries
Del Brutto, Oscar H.; Nash, Theodore E.; Garcia, Hector H.
2012-01-01
Objective Review of case reports and case series of patients with single cysticercus granulomas in non-endemic countries to determine the characteristics of this form of neurocysticercosis in these regions. Methods MEDLINE and manual search of patients with single cysticercus granulomas diagnosed in non-endemic countries from 1991 to 2011. Abstracted data included: demographic profile, clinical manifestations, form of neurocysticercosis, and whether the disease occurred in immigrants, international travelers, or citizens from non-endemic countries who had never been abroad. Results A total of 77 patients were found. Of these, 61 (79%) were diagnosed since the year 2000. Thirty-four patients (44%) patients were immigrants from endemic countries, 18 (23%) were international travelers returning from disease-endemic areas, and the remaining 25 (33%) were citizens from non-endemic countries who had never been abroad. Most immigrants and international travelers became symptomatic two or more years after returning home. Countries with the most reported patients were Kuwait (n=18), UK (n=11), Australia (n=8), USA (n=7), Japan (n=6), and Israel (n=5). Conclusions A single cerebral cysticercus granuloma in a non-endemic country is not a rare event. As seen in endemic regions, these cases have a good prognosis although more surgical procedures are performed in non-endemic countries, likely reflecting a decrease of diagnostic suspicion for cysticercosis and an increased availability of surgical options. The mean age of the reported cases was 25 years, and immigrants most often developed the disease greater than two years after arrival into a non-endemic area, suggesting a significant delay between infection and symptoms. However, some may have been infected and developed the disease while residing in non-endemic countries. PMID:22658897
-
[Toxic nephropathy secondary to occupational exposure to metallic mercury].
Voitzuk, Ana; Greco, Vanina; Caputo, Daniel; Alvarez, Estela
2014-01-01
Toxic nephrophaties secondary to occupational exposure to metals have been widely studied, including membranous nephropathy by mercury, which is rare. Occupational poisoning by mercury is frequent, neurological symptoms are the main form of clinical presentation. Secondary renal involvement in chronic exposure to metallic mercury can cause glomerular disease by deposit of immune-complexes. Membranous glomerulopathy and minimal change disease are the most frequently reported forms. Here we describe the case of a patient with occupational exposure to metallic mercury, where nephrotic syndrome due to membranous glomerulonephritis responded favorably to both chelation and immunosuppressive therapy.
-
Vancomycin-Associated Cast Nephropathy
Luque, Yosu; Louis, Kevin; Jouanneau, Chantal; Placier, Sandrine; Esteve, Emmanuel; Bazin, Dominique; Rondeau, Eric; Letavernier, Emmanuel; Wolfromm, Alice; Gosset, Clément; Boueilh, Anna; Burbach, Maren; Frère, Perrine; Verpont, Marie-Christine; Vandermeersch, Sophie; Langui, Dominique; Daudon, Michel; Frochot, Vincent
2017-01-01
Vancomycin is a widely prescribed antibiotic, but the exact nature of vancomycin-associated nephrotoxicity is unclear, in particular when considering the frequent coadministration of aminoglycosides. We describe here the initial case of a 56-year-old woman with normal renal function developing unexplained ARF without hypovolemia after administration of vancomycin without coadministration of aminoglycosides. Studying the patient’s renal biopsy specimen, we ascertained that obstructive tubular casts composed of noncrystal nanospheric vancomycin aggregates entangled with uromodulin explained the vancomycin-associated ARF. We developed in parallel a new immunohistologic staining technique to detect vancomycin in renal tissue and confirmed retrospectively that deleterious vancomycin-associated casts existed in eight additional patients with acute tubular necrosis in the absence of hypovolemia. Concomitant high vancomycin trough plasma levels had been observed in each patient. We also reproduced experimentally the toxic and obstructive nature of vancomycin-associated cast nephropathy in mice, which we detected using different in vivo imaging techniques. In conclusion, the interaction of uromodulin with nanospheric vancomycin aggregates represents a new mode of tubular cast formation, revealing the hitherto unsuspected mechanism of vancomycin-associated renal injury. PMID:28082518
-
Vancomycin-Associated Cast Nephropathy.
Luque, Yosu; Louis, Kevin; Jouanneau, Chantal; Placier, Sandrine; Esteve, Emmanuel; Bazin, Dominique; Rondeau, Eric; Letavernier, Emmanuel; Wolfromm, Alice; Gosset, Clément; Boueilh, Anna; Burbach, Maren; Frère, Perrine; Verpont, Marie-Christine; Vandermeersch, Sophie; Langui, Dominique; Daudon, Michel; Frochot, Vincent; Mesnard, Laurent
2017-06-01
Vancomycin is a widely prescribed antibiotic, but the exact nature of vancomycin-associated nephrotoxicity is unclear, in particular when considering the frequent coadministration of aminoglycosides. We describe here the initial case of a 56-year-old woman with normal renal function developing unexplained ARF without hypovolemia after administration of vancomycin without coadministration of aminoglycosides. Studying the patient's renal biopsy specimen, we ascertained that obstructive tubular casts composed of noncrystal nanospheric vancomycin aggregates entangled with uromodulin explained the vancomycin-associated ARF. We developed in parallel a new immunohistologic staining technique to detect vancomycin in renal tissue and confirmed retrospectively that deleterious vancomycin-associated casts existed in eight additional patients with acute tubular necrosis in the absence of hypovolemia. Concomitant high vancomycin trough plasma levels had been observed in each patient. We also reproduced experimentally the toxic and obstructive nature of vancomycin-associated cast nephropathy in mice, which we detected using different in vivo imaging techniques. In conclusion, the interaction of uromodulin with nanospheric vancomycin aggregates represents a new mode of tubular cast formation, revealing the hitherto unsuspected mechanism of vancomycin-associated renal injury. Copyright © 2017 by the American Society of Nephrology.
-
Wang, Minghui; Liu, Shanying; Ouyang, Nengtai; Song, Erwei; Lutz, Jens; Heemann, Uwe
2004-09-01
Lymphocytic infiltration is obvious throughout early and late stages of chronic allograft nephropathy. Early infiltrating lymphocytes are involved in initial insults to kidney allografts, but the contribution of late infiltration to long-term allograft attrition is still controversial. Early application of FTY720 reduced the number of graft infiltrating lymphocytes, and inhibited acute rejection. The present study investigated the potential of FTY720 to reduce the number of infiltrating lymphocytes even at a late stage, and, thus, slow the pace of chronic allograft nephropathy. Fisher (F344) rat kidneys were orthotopically transplanted into Lewis recipients with an initial 10-day course of cyclosporine A (1.5 mg/kg/day). FTY720, at a dose of 0.5 mg/kg/day, or vehicle was administered to recipients either from weeks 12 to 24 or from 20 to 24 after transplantation. Animals were harvested 24 weeks after transplantation for histologic, immunohistologic, and molecular analysis. FTY720, either initiated at 12 or 20 weeks after transplantation, reduced urinary protein excretion, and significantly ameliorated glomerulosclerosis, interstitial fibrosis, tubular atrophy, and intimal proliferation of graft arteries at 24 weeks after transplantation. Furthermore FTY720 markedly suppressed lymphocyte infiltration and decreased mRNA levels of interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), and platelet-derived growth factor-B (PDGF-B) but enhanced the number of apoptotic cells in grafts. FTY720 ameliorated chronic allograft nephropathy even at advanced stages. Furthermore, our data suggest that this effect was achieved by a reduction of graft infiltrating lymphocytes.
-
Li, Xu; Zhang, Lei; Chen, Haibing; Guo, Kaifeng; Yu, Haoyong; Zhou, Jian; Li, Ming; Li, Qing; Li, Lianxi; Yin, Jun; Liu, Fang; Bao, Yuqian; Han, Junfeng; Jia, Weiping
2017-03-31
Recent studies highlight a negative association between total bilirubin concentrations and albuminuria in patients with type 2 diabetes mellitus. Our study evaluated the relationship between bilirubin concentrations and the prevalence of diabetic nephropathy (DN) in Chinese patients with type 1 diabetes mellitus (T1DM). A total of 258 patients with T1DM were recruited and bilirubin concentrations were compared between patients with or without diabetic nephropathy. Multiple stepwise regression analysis was used to examine the relationship between bilirubin concentrations and 24 h urinary microalbumin. Binary logistic regression analysis was performed to assess independent risk factors for diabetic nephropathy. Participants were divided into four groups according to the quartile of total bilirubin concentrations (Q1, 0.20-0.60; Q2, 0.60-0.80; Q3, 0.80-1.00; Q4, 1.00-1.90 mg/dL) and the chi-square test was used to compare the prevalence of DN in patients with T1DM. The median bilirubin level was 0.56 (interquartile: 0.43-0.68 mg/dL) in the DN group, significantly lower than in the non-DN group (0.70 [interquartile: 0.58-0.89 mg/dL], P < 0.001). Spearman's correlational analysis showed bilirubin concentrations were inversely correlated with 24 h urinary microalbumin (r = -0.13, P < 0.05) and multiple stepwise regression analysis showed bilirubin concentrations were independently associated with 24 h urinary microalbumin. In logistic regression analysis, bilirubin concentrations were significantly inversely associated with nephropathy. In addition, in stratified analysis, from the first to the fourth quartile group, increased bilirubin concentrations were associated with decreased prevalence of DN from 21.90% to 2.00%. High bilirubin concentrations are independently and negatively associated with albuminuria and the prevalence of DN in patients with T1DM.
-
Trimarchi, Hernán; Muryan, Alexis; Young, Pablo; Forrester, Mariano; Iotti, Alejandro; Pereyra, Horacio; Lombi, Fernando; Seminario, Omar; Alonso, Mirta; Iotti, Roberto
2007-01-01
Renin-angiotensin system inhibition is a widely accepted approach to initially deal with proteinuria in IgA nephropathy, while the role of immunosuppressants remains controversial in many instances. A prospective, uncontrolled, open-label trial was undertaken in patients with biopsy-proven IgA nephropathy with proteinuria > 0.5 g/day and normal renal function to assess the efficacy of a combination treatment of angiotensin converting enzyme inhibitors plus angiotensin receptor blockers enalapril valsartan coupled with methylprednisone to decrease proteinuria to levels below 0.5 g/day. Twenty patients were included: Age 37.45 +/- 13.26 years (50% male); 7 patients (35%) were hypertensive; proteinuria 2.2 +/- 1.86 g/day; serum creatinine 1.07 +/- 0.29 mg/dl; mean follow-up 60.10 +/- 31.47 months. IgA nephropathy was subclassified according to Haas criteria. Twelve patients (60%) were class II; seven (35%) were class III and one (5%) class V. All patients received dual renin-angiotensin system blockade as tolerated. Oral methylprednisone was started at 0.5 mg/kg/day for the initial 8 weeks and subsequently tapered bi-weekly until the maintenance dose of 4 mg was reached. Oral steroids were discontinued after 24 weeks (6 months) of therapy but renin-angiotensin inhibition remained unchanged. At 10 weeks of therapy proteinuria decreased to 0.15 +/- 0.07 g/day (P < 0.001) while serum creatinine did not vary: 1.07 +/- 0.28 mg/dl (P = ns). After a mean follow-up of 42.36 +/- 21.56 months urinary protein excretion (0.12 +/- 0.06 g/day) and renal function (serum creatinine 1.06 +/- 0.27 mg/dl) remained stable. No major side effects were reported during the study. Renin-angiotensin blockade plus oral steroids proved useful to significantly decrease proteinuria to < 0.5 g/day in patients with IgA nephropathy without changes in renal function.
-
Adler, Amanda I; Stevens, Richard J; Manley, Sue E; Bilous, Rudy W; Cull, Carole A; Holman, Rury R
2003-01-01
The progression of nephropathy from diagnosis of type 2 diabetes has not been well described from a single population. This study sought to describe the development and progression through the stages of microalbuminuria, macroalbuminuria, persistently elevated plasma creatinine or renal replacement therapy (RRT), and death. Using observed and modeled data from 5097 subjects in the UK Prospective Diabetes Study, we measured the annual probability of transition from stage to stage (incidence), prevalence, cumulative incidence, ten-year survival, median duration per stage, and risk of death from all-causes or cardiovascular disease. From diagnosis of diabetes, progression to microalbuminuria occurred at 2.0% per year, from microalbuminuria to macroalbuminuria at 2.8% per year, and from macroalbuminuria to elevated plasma creatinine (>or=175 micromol/L) or renal replacement therapy at 2.3% per year. Ten years following diagnosis of diabetes, the prevalence of microalbuminuria was 24.9%, of macroalbuminuria was 5.3%, and of elevated plasma creatinine or RRT was 0.8%. Patients with elevated plasma creatinine or RRT had an annual death rate of 19.2% (95% confidence interval, CI, 14.0 to 24.4%). There was a trend for increasing risk of cardiovascular death with increasing nephropathy (P < 0.0001), with an annual rate of 0.7% for subjects in the stage of no nephropathy, 2.0% for those with microalbuminuria, 3.5% for those with macroalbuminuria, and 12.1% with elevated plasma creatinine or RRT. Individuals with macroalbuminuria were more likely to die in any year than to develop renal failure. The proportion of patients with type 2 diabetes who develop microalbuminuria is substantial with one quarter affected by 10 years from diagnosis. Relatively fewer patients develop macroalbuminuria, but in those who do, the death rate exceeds the rate of progression to worse nephropathy.
-
Yajima, A.; Gabrielli, A. F.; Montresor, A.; Engels, D.
2017-01-01
The authors conducted a systematic literature review with the following aims: (i) to investigate how frequently soil-transmitted helminthiasis (STH) infections are endemic where schistosomiasis is present; and (ii) to assess the correlation between the risk level of schistosomiasis and that of STH. Among 155 sites on which data were collected and analyzed, schistosomiasis was present in 130 sites, all of which were also co-endemic for STH, whereas 25 sites were endemic only for STH. Out of 83 sites where at least one biannual round of preventive chemotherapy (PC) for schistosomiasis is recommended, 94% were also eligible for at least a yearly round of PC against STH. And among 21 sites where PC for schistosomiasis is recommended once a year, 81% were also eligible for at least a yearly round of PC for STH. This fact provides managers of control programmes with the operationally important indication that use of available information on endemicity of schistosomiasis is a valid tool to predict the presence of STH in the same geographical area as well as to estimate the need of PC for STH. The implementation of this tool is expected to save financial and human resources and help accelerate the scale-up of PC throughout the world. PMID:21215979
-
Delineation of an endemic tick paralysis zone in southeastern Australia.
Whitfield, Zoe; Kelman, Mark; Ward, Michael P
2017-11-30
Tick paralysis has a major impact on pet dog and cat populations in southeastern Australia. It results from envenomation by Ixodes holocyclus and Ixodes cornuatus ticks, the role of Ixodes cornuatus in the epidemiology of this disease in Australia being unclear. The aim of this study was to describe the geographical distribution of tick paralysis cases in southeastern Australia using data from a national disease surveillance system and to compare characteristics of "endemic" cases with those reported outside this endemic zone ("sporadic" cases). Data were collated and a proportional symbol map of all cases by postcode was created. A 15-case isopleth was developed based on descriptive spatial statistics (directional ellipses) and then kernel smoothing to distinguish endemic from sporadic cases. During the study period (January 2010-December 2015) 12,421 cases were reported, and 10,839 of these reported by clinics located in 434 postcodes were included in the study. Endemic cases were predominantly reported from postcodes in coastal southeastern Australia, from southern Queensland to eastern Victoria. Of those cases meeting selection criteria, within the endemic zone 10,767 cases were reported from 351 (88%) postcodes and outside this zone 72 cases were reported from 48 (12%) postcodes. Of these latter 48 postcodes, 18 were in Victoria (26 cases), 16 in New South Wales (28 cases), 7 in Tasmania (9 cases), 5 in South Australia (7 cases) and 2 in Queensland (2 cases). Seasonal distribution in reporting was found: 62% of endemic and 52% of sporadic cases were reported in spring. The number of both endemic and sporadic cases reported peaked in October and November, but importantly a secondary peak in reporting of sporadic cases in April was found. In non-endemic areas, summer was the lowest risk season whilst in endemic areas, autumn was the lowest risk season. Two clusters of sporadic cases were identified, one in South Australia (P=0.022) during the period 22 May to 2
-
Targeted deletion of kidney glucose-6 phosphatase leads to nephropathy.
Clar, Julie; Gri, Blandine; Calderaro, Julien; Birling, Marie-Christine; Hérault, Yann; Smit, G Peter A; Mithieux, Gilles; Rajas, Fabienne
2014-10-01
Renal failure is a major complication that arises with aging in glycogen storage disease type 1a and type 1b patients. In the kidneys, glucose-6 phosphatase catalytic subunit (encoded by G6pc) deficiency leads to the accumulation of glycogen, an effect resulting in marked nephromegaly and progressive glomerular hyperperfusion and hyperfiltration preceding the development of microalbuminuria and proteinuria. To better understand the end-stage nephropathy in glycogen storage disease type 1a, we generated a novel kidney-specific G6pc knockout (K-G6pc(-/-)) mouse, which exhibited normal life expectancy. After 6 months, K-G6pc(-/-) mice showed glycogen overload leading to nephromegaly and tubular dilation. Moreover, renal accumulation of lipids due to activation of de novo lipogenesis was observed. This led to the activation of the renin-angiotensin system and the development of epithelial-mesenchymal transition process and podocyte injury by transforming growth factor β1 signaling. The K-G6pc(-/-) mice developed microalbuminuria caused by the impairment of the glomerular filtration barrier. Thus, renal G6pc deficiency alone is sufficient to induce the development of the early-onset nephropathy observed in glycogen storage disease type 1a, independent of the liver disease. The K-G6pc(-/-) mouse model is a unique tool to decipher the molecular mechanisms underlying renal failure and to evaluate potential therapeutic strategies.
-
The RAAS in the pathogenesis and treatment of diabetic nephropathy.
Ruggenenti, Piero; Cravedi, Paolo; Remuzzi, Giuseppe
2010-06-01
Angiotensin II and other components of the renin-angiotensin-aldosterone system (RAAS) have a central role in the pathogenesis and progression of diabetic renal disease. A study in patients with type 1 diabetes and overt nephropathy found that RAAS inhibition with angiotensin-converting-enzyme (ACE) inhibitors was associated with a reduced risk of progression to end-stage renal disease and mortality compared with non-RAAS-inhibiting drugs. Blood-pressure control was similar between groups and proteinuria reduction was responsible for a large part of the renoprotective and cardioprotective effect. ACE inhibitors can also prevent microalbuminuria in patients with type 2 diabetes who are hypertensive and normoalbuminuric; in addition, ACE inhibitors are cardioprotective even in the early stages of diabetic renal disease. Angiotensin-II-receptor blockers (ARBs) are renoprotective (but not cardioprotective) in patients with type 2 diabetes and overt nephropathy or microalbuminuria. Studies have evaluated the renoprotective effect of other RAAS inhibitors, such as aldosterone antagonists and renin inhibitors, administered either alone or in combination with ACE inhibitors or ARBs. An important task for the future will be identifying which combination of agents achieves the best renoprotection (and cardioprotection) at the lowest cost. Such findings will have major implications, particularly in settings where money and facilities are limited and in settings where renal replacement therapy is not available and the prevention of kidney failure is life saving.
-
Plant and animal endemism in the eastern Andean slope: challenges to conservation.
Swenson, Jennifer J; Young, Bruce E; Beck, Stephan; Comer, Pat; Córdova, Jesús H; Dyson, Jessica; Embert, Dirk; Encarnación, Filomeno; Ferreira, Wanderley; Franke, Irma; Grossman, Dennis; Hernandez, Pilar; Herzog, Sebastian K; Josse, Carmen; Navarro, Gonzalo; Pacheco, Víctor; Stein, Bruce A; Timaná, Martín; Tovar, Antonio; Tovar, Carolina; Vargas, Julieta; Zambrana-Torrelio, Carlos M
2012-01-27
The Andes-Amazon basin of Peru and Bolivia is one of the most data-poor, biologically rich, and rapidly changing areas of the world. Conservation scientists agree that this area hosts extremely high endemism, perhaps the highest in the world, yet we know little about the geographic distributions of these species and ecosystems within country boundaries. To address this need, we have developed conservation data on endemic biodiversity (~800 species of birds, mammals, amphibians, and plants) and terrestrial ecological systems (~90; groups of vegetation communities resulting from the action of ecological processes, substrates, and/or environmental gradients) with which we conduct a fine scale conservation prioritization across the Amazon watershed of Peru and Bolivia. We modelled the geographic distributions of 435 endemic plants and all 347 endemic vertebrate species, from existing museum and herbaria specimens at a regional conservation practitioner's scale (1:250,000-1:1,000,000), based on the best available tools and geographic data. We mapped ecological systems, endemic species concentrations, and irreplaceable areas with respect to national level protected areas. We found that sizes of endemic species distributions ranged widely (< 20 km2 to > 200,000 km2) across the study area. Bird and mammal endemic species richness was greatest within a narrow 2500-3000 m elevation band along the length of the Andes Mountains. Endemic amphibian richness was highest at 1000-1500 m elevation and concentrated in the southern half of the study area. Geographical distribution of plant endemism was highly taxon-dependent. Irreplaceable areas, defined as locations with the highest number of species with narrow ranges, overlapped slightly with areas of high endemism, yet generally exhibited unique patterns across the study area by species group. We found that many endemic species and ecological systems are lacking national-level protection; a third of endemic species have
-
Plant and animal endemism in the eastern Andean slope: challenges to conservation
2012-01-01
Background The Andes-Amazon basin of Peru and Bolivia is one of the most data-poor, biologically rich, and rapidly changing areas of the world. Conservation scientists agree that this area hosts extremely high endemism, perhaps the highest in the world, yet we know little about the geographic distributions of these species and ecosystems within country boundaries. To address this need, we have developed conservation data on endemic biodiversity (~800 species of birds, mammals, amphibians, and plants) and terrestrial ecological systems (~90; groups of vegetation communities resulting from the action of ecological processes, substrates, and/or environmental gradients) with which we conduct a fine scale conservation prioritization across the Amazon watershed of Peru and Bolivia. We modelled the geographic distributions of 435 endemic plants and all 347 endemic vertebrate species, from existing museum and herbaria specimens at a regional conservation practitioner's scale (1:250,000-1:1,000,000), based on the best available tools and geographic data. We mapped ecological systems, endemic species concentrations, and irreplaceable areas with respect to national level protected areas. Results We found that sizes of endemic species distributions ranged widely (< 20 km2 to > 200,000 km2) across the study area. Bird and mammal endemic species richness was greatest within a narrow 2500-3000 m elevation band along the length of the Andes Mountains. Endemic amphibian richness was highest at 1000-1500 m elevation and concentrated in the southern half of the study area. Geographical distribution of plant endemism was highly taxon-dependent. Irreplaceable areas, defined as locations with the highest number of species with narrow ranges, overlapped slightly with areas of high endemism, yet generally exhibited unique patterns across the study area by species group. We found that many endemic species and ecological systems are lacking national-level protection; a third of endemic
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Levova, Katerina; Moserova, Michaela; Nebert, Daniel W.
Aristolochic acid causes a specific nephropathy (AAN), Balkan endemic nephropathy, and urothelial malignancies. Using Western blotting suitable to determine protein expression, we investigated in several transgenic mouse lines expression of NAD(P)H:quinone oxidoreductase (NQO1)—the most efficient cytosolic enzyme that reductively activates aristolochic acid I (AAI). The mouse tissues used were from previous studies [Arlt et al., Chem. Res. Toxicol. 24 (2011) 1710; Stiborova et al., Toxicol. Sci. 125 (2012) 345], in which the role of microsomal cytochrome P450 (CYP) enzymes in AAI metabolism in vivo had been determined. We found that NQO1 levels in liver, kidney and lung of Cyp1a1(−/−), Cyp1a2(−/−)more » and Cyp1a1/1a2(−/−) knockout mouse lines, as well as in two CYP1A-humanized mouse lines harboring functional human CYP1A1 and CYP1A2 and lacking the mouse Cyp1a1/1a2 orthologs, differed from NQO1 levels in wild-type mice. NQO1 protein and enzymic activity were induced in hepatic and renal cytosolic fractions isolated from AAI-pretreated mice, compared with those in untreated mice. Furthermore, this increase in hepatic NQO1 enzyme activity was associated with bioactivation of AAI and elevated AAI-DNA adduct levels in ex vivo incubations of cytosolic fractions with DNA and AAI. In conclusion, AAI appears to increase its own metabolic activation by inducing NQO1, thereby enhancing its own genotoxic potential. Highlights: ► NAD(P)H:quinone oxidoreductase expression in Cyp1a knockout and humanized CYP1A mice ► Reductive activation of the nephrotoxic and carcinogenic aristolochic acid I (AAI) ► NAD(P)H:quinone oxidoreductase is induced in mice treated with AAI. ► Induced hepatic enzyme activity resulted in elevated AAI-DNA adduct levels.« less
-
Arlt, Volker M; Meinl, Walter; Florian, Simone; Nagy, Eszter; Barta, Frantisek; Thomann, Marlies; Mrizova, Iveta; Krais, Annette M; Liu, Maggie; Richards, Meirion; Mirza, Amin; Kopka, Klaus; Phillips, David H; Glatt, Hansruedi; Stiborova, Marie; Schmeiser, Heinz H
2017-04-01
Exposure to aristolochic acid (AA) causes aristolochic acid nephropathy (AAN) and Balkan endemic nephropathy (BEN). Conflicting results have been found for the role of human sulfotransferase 1A1 (SULT1A1) contributing to the metabolic activation of aristolochic acid I (AAI) in vitro. We evaluated the role of human SULT1A1 in AA bioactivation in vivo after treatment of transgenic mice carrying a functional human SULT1A1-SULT1A2 gene cluster (i.e. hSULT1A1/2 mice) and Sult1a1(-/-) mice with AAI and aristolochic acid II (AAII). Both compounds formed characteristic DNA adducts in the intact mouse and in cytosolic incubations in vitro. However, we did not find differences in AAI-/AAII-DNA adduct levels between hSULT1A1/2 and wild-type (WT) mice in all tissues analysed including kidney and liver despite strong enhancement of sulfotransferase activity in both kidney and liver of hSULT1A1/2 mice relative to WT, kidney and liver being major organs involved in AA metabolism. In contrast, DNA adduct formation was strongly increased in hSULT1A1/2 mice compared to WT after treatment with 3-nitrobenzanthrone (3-NBA), another carcinogenic aromatic nitro compound where human SULT1A1/2 is known to contribute to genotoxicity. We found no differences in AAI-/AAII-DNA adduct formation in Sult1a1(-/-) and WT mice in vivo. Using renal and hepatic cytosolic fractions of hSULT1A1/2, Sult1a1(-/-) and WT mice, we investigated AAI-DNA adduct formation in vitro but failed to find a contribution of human SULT1A1/2 or murine Sult1a1 to AAI bioactivation. Our results indicate that sulfo-conjugation catalysed by human SULT1A1 does not play a role in the activation pathways of AAI and AAII in vivo, but is important in 3-NBA bioactivation.
-
Emerging therapeutics for the treatment of diabetic nephropathy.
Brenneman, Jehrod; Hill, Jon; Pullen, Steve
2016-09-15
Diabetic nephropathy (DN) is the most common pathology contributing to the development of chronic kidney disease (CKD). DN caused by hypertension and unmitigated inflammation in diabetics, renders the kidneys unable to perform normally, and leads to renal fibrosis and organ failure. The increasing global prevalence of DN has been directly attributed to rising incidences of Type II diabetes, and is now the largest non-communicable cause of death worldwide. Despite the high morbidity, successful new treatments for DN are lacking. This review seeks to provide new insight on emerging clinical candidates under investigation for the treatment of DN. Copyright © 2016 Elsevier Ltd. All rights reserved.
-
Complex networks analysis of obstructive nephropathy data
NASA Astrophysics Data System (ADS)
Zanin, M.; Boccaletti, S.
2011-09-01
Congenital obstructive nephropathy (ON) is one of the most frequent and complex diseases affecting children, characterized by an abnormal flux of the urine, due to a partial or complete obstruction of the urinary tract; as a consequence, urine may accumulate in the kidney and disturb the normal operation of the organ. Despite important advances, pathological mechanisms are not yet fully understood. In this contribution, the topology of complex networks, based on vectors of features of control and ON subjects, is related with the severity of the pathology. Nodes in these networks represent genetic and metabolic profiles, while connections between them indicate an abnormal relation between their expressions. Resulting topologies allow discriminating ON subjects and detecting which genetic or metabolic elements are responsible for the malfunction.
-
The serum uric acid concentration is not causally linked to diabetic nephropathy in type 1 diabetes.
Ahola, Aila J; Sandholm, Niina; Forsblom, Carol; Harjutsalo, Valma; Dahlström, Emma; Groop, Per-Henrik
2017-05-01
Previous studies have shown a relationship between uric acid concentration and progression of renal disease. Here we studied causality between the serum uric acid concentration and progression of diabetic nephropathy in 3895 individuals with type 1 diabetes in the FinnDiane Study. The renal status was assessed with the urinary albumin excretion rate and estimated glomerular filtration rate (eGFR) at baseline and at the end of the follow-up. Based on previous genomewide association studies on serum uric acid concentration, 23 single nucleotide polymorphisms (SNPs) with good imputation quality were selected for the SNP score. This score was used to assess the causality between serum uric acid and renal complications using a Mendelian randomization approach. At baseline, the serum uric acid concentration was higher with worsening renal status. In multivariable Cox regression analyses, baseline serum uric acid concentration was not independently associated with progression of diabetic nephropathy over a mean follow-up of 7 years. However, over the same period, baseline serum uric acid was independently associated with the decline in eGFR. In the cross-sectional logistic regression analyses, the SNP score was associated with the serum uric acid concentration. Nevertheless, the Mendelian randomization showed no causality between uric acid and diabetic nephropathy, eGFR categories, or eGFR as a continuous variable. Thus, our results suggest that the serum uric acid concentration is not causally related to diabetic nephropathy but is a downstream marker of kidney damage. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
-
Ahola, Aila J; Harjutsalo, Valma; Forsblom, Carol; Groop, Per-Henrik
2014-08-01
Hypertension and depression are frequent comorbidities of diabetes. Studies suggest that antihypertensive medication affecting the renin-angiotensin-aldosterone system (RAAS) might also relieve depression. Whether this is also seen in patients with type 1 diabetes is not known. We therefore studied whether use of RAAS-modifying medication is associated with reduced antidepressant use in type 1 diabetes. In all, 1,705 participants in the FinnDiane Study were included (57 % men, mean age 46 ± 11 years). Data on medications were obtained from the Drug Prescription Register. Based on their albumin excretion rate (AER), the patients were classified as having normal AER, microalbuminuria, or macroalbuminuria. Diabetic nephropathy was defined as macroalbuminuria or end-stage renal disease (dialysis or renal transplant). A total of 8.4 and 10.9 % of patients with and without RAAS-modifying medication, respectively, had antidepressant medication purchases (NS). In logistic regression analysis, after adjusting for potential confounding factors, use of RAAS-modifying medication was not associated with antidepressant purchases. However, when patients with and without diabetic nephropathy were analyzed separately, RAAS-modifying medication was associated with lower frequency of antidepressant purchases among patients with established diabetic nephropathy. In conclusion, use of RAAS-modifying medication may improve mood in patients with type 1 diabetes and established diabetic nephropathy.
-
Nanmoku, Koji; Kurosawa, Akira; Shinzato, Takahiro; Shimizu, Toshihiro; Kimura, Takaaki; Yagisawa, Takashi
2017-01-01
Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder that results in irreversible renal damage due to 2,8-dihydroxyadenine (DHA) nephropathy. A 28-year-old man underwent living-related kidney transplantation for chronic kidney disease of unknown etiology. Numerous spherical brownish crystals observed in his urinary sediment on postoperative day 3 and were observed within the tubular lumen of renal allograft biopsy specimens on postoperative day 7. After a genetic diagnosis, febuxostat treatment was started on postoperative day 7, with the dosage gradually increased to 80 mg/day until complete the disappearance of 2,8-DHA crystals. Febuxostat prevented secondary 2,8-DHA nephropathy after kidney transplantation.
-
Nanmoku, Koji; Kurosawa, Akira; Shinzato, Takahiro; Shimizu, Toshihiro; Kimura, Takaaki; Yagisawa, Takashi
2017-01-01
Adenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder that results in irreversible renal damage due to 2,8-dihydroxyadenine (DHA) nephropathy. A 28-year-old man underwent living-related kidney transplantation for chronic kidney disease of unknown etiology. Numerous spherical brownish crystals observed in his urinary sediment on postoperative day 3 and were observed within the tubular lumen of renal allograft biopsy specimens on postoperative day 7. After a genetic diagnosis, febuxostat treatment was started on postoperative day 7, with the dosage gradually increased to 80 mg/day until complete the disappearance of 2,8-DHA crystals. Febuxostat prevented secondary 2,8-DHA nephropathy after kidney transplantation. PMID:28566603
-
Kesari, Shreekant; Bhunia, Gouri Sankar; Kumar, Vijay; Jeyaram, Algarswamy; Ranjan, Alok; Das, Pradeep
2011-08-01
In visceral leishmaniasis, phlebotomine vectors are targets for control measures. Understanding the ecosystem of the vectors is a prerequisite for creating these control measures. This study endeavours to delineate the suitable locations of Phlebotomus argentipes with relation to environmental characteristics between endemic and non-endemic districts in India. A cross-sectional survey was conducted on 25 villages in each district. Environmental data were obtained through remote sensing images and vector density was measured using a CDC light trap. Simple linear regression analysis was used to measure the association between climatic parameters and vector density. Using factor analysis, the relationship between land cover classes and P. argentipes density among the villages in both districts was investigated. The results of the regression analysis indicated that indoor temperature and relative humidity are the best predictors for P. argentipes distribution. Factor analysis confirmed breeding preferences for P. argentipes by landscape element. Minimum Normalised Difference Vegetation Index, marshy land and orchard/settlement produced high loading in an endemic region, whereas water bodies and dense forest were preferred in non-endemic sites. Soil properties between the two districts were studied and indicated that soil pH and moisture content is higher in endemic sites compared to non-endemic sites. The present study should be utilised to make critical decisions for vector surveillance and controlling Kala-azar disease vectors.
-
Systemic Epstein-Barr virus infection associated with membranous nephropathy in children.
Araya, C E; González-Peralta, R P; Skoda-Smith, S; Dharnidharka, V R
2006-03-01
Epstein-Barr virus (EBV) infection can cause diverse renal manifestations ranging from microscopic hematuria to acute renal failure. Membranous nephropathy (MN) is an uncommon and usually secondary cause of nephrotic syndrome in children, and has been reported after chronic infections and antigenemia. We report two pediatric cases of secondary MN associated with acute and chronic systemic EBV infection. Patient 1 had a liver transplant for cirrhosis due to biliary atresia and developed chronic EB viremia. Membranous nephropathy occurred 3 years later and with aggressive therapy has partially subsided, in temporal association with a drop in blood EBV PCR levels. The other patient had a primary immunodeficiency and developed a lymphoproliferative disorder attributed to EBV. Nephrotic syndrome developed at initial presentation and was associated with MN on biopsy. The patient cleared the virus from blood, which was associated with eventual resolution of the MN. We postulate that EB viremia in patients lacking a fully competent immune system, but without a renal allograft, may create a susceptible environment for chronic systemic EB antigenemia that can then lead to immune-complex MN in the kidney. The association of EBV with renal histological changes consistent with MN has been suggested but not directly described before.
-
Proteases and protease inhibitors of urinary extracellular vesicles in diabetic nephropathy.
Musante, Luca; Tataruch, Dorota; Gu, Dongfeng; Liu, Xinyu; Forsblom, Carol; Groop, Per-Henrik; Holthofer, Harry
2015-01-01
Diabetic nephropathy (DN) is one of the major complications of diabetes mellitus (DM), leads to chronic kidney disease (CKD), and, ultimately, is the main cause for end-stage kidney disease (ESKD). Beyond urinary albumin, no reliable biomarkers are available for accurate early diagnostics. Urinary extracellular vesicles (UEVs) have recently emerged as an interesting source of diagnostic and prognostic disease biomarkers. Here we used a protease and respective protease inhibitor array to profile urines of type 1 diabetes patients at different stages of kidney involvement. Urine samples were divided into groups based on the level of albuminuria and UEVs isolated by hydrostatic dialysis and screened for relative changes of 34 different proteases and 32 protease inhibitors, respectively. Interestingly, myeloblastin and its natural inhibitor elafin showed an increase in the normo- and microalbuminuric groups. Similarly, a characteristic pattern was observed in the array of protease inhibitors, with a marked increase of cystatin B, natural inhibitor of cathepsins L, H, and B as well as of neutrophil gelatinase-associated Lipocalin (NGAL) in the normoalbuminuric group. This study shows for the first time the distinctive alterations in comprehensive protease profiles of UEVs in diabetic nephropathy and uncovers intriguing mechanistic, prognostic, and diagnostic features of kidney damage in diabetes.
-
Proteases and Protease Inhibitors of Urinary Extracellular Vesicles in Diabetic Nephropathy
Tataruch, Dorota; Gu, Dongfeng; Liu, Xinyu; Forsblom, Carol; Groop, Per-Henrik; Holthofer, Harry
2015-01-01
Diabetic nephropathy (DN) is one of the major complications of diabetes mellitus (DM), leads to chronic kidney disease (CKD), and, ultimately, is the main cause for end-stage kidney disease (ESKD). Beyond urinary albumin, no reliable biomarkers are available for accurate early diagnostics. Urinary extracellular vesicles (UEVs) have recently emerged as an interesting source of diagnostic and prognostic disease biomarkers. Here we used a protease and respective protease inhibitor array to profile urines of type 1 diabetes patients at different stages of kidney involvement. Urine samples were divided into groups based on the level of albuminuria and UEVs isolated by hydrostatic dialysis and screened for relative changes of 34 different proteases and 32 protease inhibitors, respectively. Interestingly, myeloblastin and its natural inhibitor elafin showed an increase in the normo- and microalbuminuric groups. Similarly, a characteristic pattern was observed in the array of protease inhibitors, with a marked increase of cystatin B, natural inhibitor of cathepsins L, H, and B as well as of neutrophil gelatinase-associated Lipocalin (NGAL) in the normoalbuminuric group. This study shows for the first time the distinctive alterations in comprehensive protease profiles of UEVs in diabetic nephropathy and uncovers intriguing mechanistic, prognostic, and diagnostic features of kidney damage in diabetes. PMID:25874235
-
Health impacts of coal and coal use: Possible solutions
Finkelman, R.B.; Orem, W.; Castranova, V.; Tatu, C.A.; Belkin, H.E.; Zheng, B.; Lerch, H.E.; Maharaj, S.V.; Bates, A.L.
2002-01-01
Coal will be a dominant energy source in both developed and developing countries for at least the first half of the 21st century. Environmental problems associated with coal, before mining, during mining, in storage, during combustion, and postcombustion waste products are well known and are being addressed by ongoing research. The connection between potential environmental problems with human health is a fairly new field and requires the cooperation of both the geoscience and medical disciplines. Three research programs that illustrate this collaboration are described and used to present a range of human health problems that are potentially caused by coal. Domestic combustion of coal in China has, in some cases, severely affected human health. Both on a local and regional scale, human health has been adversely affected by coals containing arsenic, fluorine, selenium, and possibly, mercury. Balkan endemic nephropathy (BEN), an irreversible kidney disease of unknown origin, has been related to the proximity of Pliocene lignite deposits. The working hypothesis is that groundwater is leaching toxic organic compounds as it passes through the lignites and that these organics are then ingested by the local population contributing to this health problem. Human disease associated with coal mining mainly results from inhalation of particulate matter during the mining process. The disease is Coal Worker's Pneumoconiosis characterized by coal dust-induced lesions in the gas exchange regions of the lung; the coal worker's "black lung disease". ?? 2002 Elsevier Science B.V. All rights reserved.
-
Masuda, Kana; Ujike, Haruyo; Hinamoto, Norikazu; Miyake, Hiromasa; Tanimura, Satoshi; Sugiyama, Hitoshi; Sato, Yasufumi; Maeshima, Yohei; Wada, Jun
2018-01-01
Angiogenesis has been implicated in glomerular alterations in the early stage of diabetic nephropathy. We previously reported the renoprotective effects of vasohibin-1 (VASH1), which is a novel angiogenesis inhibitor derived from endothelial cells, on diabetic nephropathy progression. Vasohibin-2 (VASH2) was originally identified as a VASH1 homolog and possesses pro-angiogenic activity in contrast to VASH1. In addition, VASH2 was recently shown to promote epithelial-to-mesenchymal transition via enhanced transforming growth factor (TGF)-β signaling in cancer cells. Herein, we investigated the pathogenic roles of VASH2 in diabetic nephropathy using VAHS2-deficient mice. The type 1 diabetes model was induced by intraperitoneal injections of streptozotocin in VASH2 homozygous knockout (VASH2LacZ/LacZ) or wild-type mice. These mice were euthanized 16 weeks after inducing hyperglycemia. Increased urine albumin excretion and creatinine clearance observed in diabetic wild-type mice were significantly prevented in diabetic VASH2-deficient mice. Accordingly, diabetes-induced increase in glomerular volume and reduction in glomerular slit-diaphragm density were significantly improved in VASH2 knockout mice. Increased glomerular endothelial area was also suppressed in VASH2-deficient mice, in association with inhibition of enhanced vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2), but not VEGF level. Furthermore, glomerular accumulation of mesangial matrix, including type IV collagen, and increased expression of TGF-β were improved in diabetic VASH2 knockout mice compared with diabetic wild-type mice. Based on the immunofluorescence findings, endogenous VASH2 localization in glomeruli was consistent with mesangial cells. Human mesangial cells (HMCs) were cultured under high glucose condition in in vitro experiments. Transfection of VASH2 small interfering RNA (siRNA) into the HMCs resulted in the suppression of type IV collagen production induced by high glucose
-
Contreras, C E; Pance, A; Marcano, N; González, N; Bianco, N
1999-06-01
Malaria antibody detection is valuable in providing retrospective confirmation of an attack of malaria. Blood bank screening is another area were malaria serology is potentially useful. In the present study, we tested the presence of antibodies to Plasmodium falciparum in sera from blood bank donors of non-endemic and malaria-endemic areas of Venezuela. Sera from 1,000 blood donors were tested by an indirect immunofluorescent antibody (IFA) assay and an IgG-ELISA for the presence of malaria antibodies using a synchronized in vitro-cultured Venezuelan isolate of P. falciparum as the antigen source. A selected group of positive and negative sera (n = 100) was also tested by a dot-IgG-ELISA. Positive results (reciprocal titer > or = 40) were found in 0.8% and 3.8% of blood donors when tested by the IFA assay and in 0.8% and 2% (optical density > or = 0.2) when tested by the IgG-ELISA in Caracas (non-endemic area) and Bolivar City (endemic area), respectively. The presence of anti-malarial antibodies in some sera from non-endemic areas such as Caracas reflects the increased potential risk of post-transfusional malaria in those areas due to the mobility of the blood donors. The data obtained indicate the need to implement new blood donor policy in blood banks in developing areas. Our results also indicate that the IFA assay is the most reliable test to use in malaria serodiagnosis.
-
Mycotic Infections Acquired outside Areas of Known Endemicity, United States.
Benedict, Kaitlin; Thompson, George R; Deresinski, Stan; Chiller, Tom
2015-11-01
In the United States, endemic mycoses--blastomycosis, coccidioidomycosis, and histoplasmosis--pose considerable clinical and public health challenges. Although the causative fungi typically exist within broadly defined geographic areas or ecologic niches, some evidence suggests that cases have occurred in humans and animals not exposed to these areas. We describe cases acquired outside regions of traditionally defined endemicity. These patients often have severe disease, but diagnosis may be delayed because of a low index of suspicion for mycotic disease, and many more cases probably go entirely undetected. Increased awareness of these diseases, with a specific focus on their potential occurrence in unusual areas, is needed. Continued interdisciplinary efforts to reevaluate and better describe areas of true endemicity are warranted, along with a more nuanced view of the notion of endemicity. The term "nonendemic" should be used with care; mycoses in such regions might more accurately be considered "not known to be endemic."
-
Guerrero-Beltrán, Carlos Enrique; Mukhopadhyay, Partha; Horváth, Béla; Rajesh, Mohanraj; Tapia, Edilia; García-Torres, Itzhel; Pedraza-Chaverri, José; Pacher, Pál
2012-05-01
Cisplatin (cis-diamminedichloroplatinum II, CIS) is a potent and widely used chemotherapeutic agent to treat various malignancies, but its therapeutic use is limited because of dose-dependent nephrotoxicity. Cell death and inflammation play a key role in the development and progression of CIS-induced nephropathy. Sulforaphane (SFN), a natural constituent of cruciferous vegetables such as broccoli, Brussels sprouts, etc., has been shown to exert various protective effects in models of tissue injury and cancer. In this study, we have investigated the role of prosurvival, cell death and inflammatory signaling pathways using a rodent model of CIS-induced nephropathy, and explored the effects of SFN on these processes. Cisplatin triggered marked activation of stress signaling pathways [p53, Jun N-terminal kinase (JNK), and p38-α mitogen-activated protein kinase (MAPK)] and promoted cell death in the kidneys (increased DNA fragmentation, caspases-3/7 activity, terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick-end labeling), associated with attenuation of various prosurvival signaling pathways [e.g., extracellular signal-regulated kinase (ERK) and p38-β MAPK]. Cisplatin also markedly enhanced inflammation in the kidneys [promoted NF-κB activation, increased expression of adhesion molecules ICAM and VCAM, enhanced tumor necrosis factor-α (TNF-α) levels and inflammatory cell infiltration]. These effects were significantly attenuated by pretreatment of rodents with SFN. Thus, the cisplatin-induced nephropathy is associated with activation of various cell death and proinflammatory pathways (p53, JNK, p38-α, TNF-α and NF-κB) and impairments of key prosurvival signaling mechanisms (ERK and p38-β). SFN is able to prevent the CIS-induced renal injury by modulating these pathways, providing a novel approach for preventing this devastating complication of chemotherapy. Published by Elsevier Inc.
-
Vaishnudevi, Durairaj; Viswanathan, Pragasam
2017-01-01
The higher risk of diabetic nephropathy (DN) leads to end stage renal diseases worldwide, which is associated with chronic inflammation. Currently, the available treatments are limited, lack of efficacy and safety. Therefore, we are in need of novel targets and advanced treatments to reduce the necessity for the renal replacement therapy and burden of this disease management. Object/Methods: In this review, we performed through an inflammatory mechanism that contribute to DN, will provide a key point to the finding off novel therapeutic agents. In addition, we discuss the current anti-inflammatory drugs, an alternative approach of seaweed polysaccharides and also exploring the future perspective of anti-inflammatory natural seaweed compounds. Currently, seaweeds are taking majority of attention from scientists for targeting the various diseases. This will become a more significant part of the pipeline and alternate medicines for anti-inflammatory and chronic diseases. The potential benefits of natural seaweed novel compounds in inhibiting inflammatory pathways would be useful for the prevention of diabetic nephropathy. Thus, this therapy manifests the clinical benefits of these compounds in the near future. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
-
Extracorporeal shock wave therapy does not improve hypertensive nephropathy.
Caron, Jonathan; Michel, Pierre-Antoine; Dussaule, Jean-Claude; Chatziantoniou, Christos; Ronco, Pierre; Boffa, Jean-Jacques
2016-06-01
Low-energy extracorporeal shock wave therapy (SWT) has been shown to improve myocardial dysfunction, hind limb ischemia, erectile function, and to facilitate cell therapy and healing process. These therapeutic effects were mainly due to promoting angiogenesis. Since chronic kidney diseases are characterized by renal fibrosis and capillaries rarefaction, they may benefit from a proangiogenic treatment. The objective of our study was to determine whether SWT could ameliorate renal repair and favor angiogenesis in L-NAME-induced hypertensive nephropathy in rats. SWT was started when proteinuria exceeded 1 g/mmol of creatinine and 1 week after L-NAME removal. SWT consisted of implying 0.09 mJ/mm(2) (400 shots), 3 times per week. After 4 weeks of SWT, blood pressure, renal function and urinary protein excretion did not differ between treated (LN + SWT) and untreated rats (LN). Histological lesions including glomerulosclerosis and arteriolosclerosis scores, tubular dilatation and interstitial fibrosis were similar in both groups. In addition, peritubular capillaries and eNOS, VEGF, VEGF-R, SDF-1 gene expressions did not increase in SWT-treated compared to untreated animals. No procedural complications or adverse effects were observed in control (C + SWT) and hypertensive rats (LN + SWT). These results suggest that extracorporeal kidney shock wave therapy does not induce angiogenesis and does not improve renal function and structure, at least in the model of hypertensive nephropathy although the treatment is well tolerated. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.
-
Early application of Met-RANTES ameliorates chronic allograft nephropathy.
Song, Erwei; Zou, Hequn; Yao, Yousheng; Proudfoot, Amanda; Antus, Balazs; Liu, Shanying; Jens, Lutz; Heemann, Uwe
2002-02-01
Initial insults to kidney allografts, characterized by infiltration of mononuclear inflammatory cells, contribute to chronic allograft nephropathy. Chemokines such as RANTES (regulated upon activation, normal T cell expressed) are thought to be responsible for the recruitment and activation of infiltrating cells. The present study investigated whether early application of Met-RANTES, a chemokine receptor antagonist that blocks the effects of RANTES, can protect renal allografts from long-term deterioration. Fisher (F344) rat kidneys were orthotopically transplanted into Lewis recipients and treated with cyclosporine A (1.5 mg/kg/day) for the first 10 days following transplantation, together with either Met-RANTES at 40 microg/day, 200 microg/day or vehicle for the first 7 days. Animals were harvested at 2 and 28 weeks after transplantation for histologic, immunohistologic and molecular analysis. Met-RANTES treatment reduced the infiltration of lymphocytes and macrophages in allografts at 2 weeks after transplantation, accompanied by decreased mRNA expression of interleukin (IL)-2, IL-1beta, tumor necrosis factor-alpha (TNF-alpha) and RANTES. At post-transplantation week 28, Met-RANTES treatment at high and low doses reduced urinary protein excretion and significantly ameliorated glomerulosclerosis, interstitial fibrosis, tubular atrophy, intimal proliferation of graft arteries and mononuclear cell infiltration. However, creatinine clearance was not influenced by Met-RANTES. Furthermore, Met-RANTES suppressed the mRNA expression of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor-B (PDGF-B). Blockade of chemokine receptors by Met-RANTES diminishes early infiltration and activation of mononuclear cells in the grafts, and thus reduces the pace of chronic allograft nephropathy.
-
Understanding the motives for food choice in Western Balkan Countries.
Milošević, Jasna; Žeželj, Iris; Gorton, Matthew; Barjolle, Dominique
2012-02-01
Substantial empirical evidence exists regarding the importance of different factors underlying food choice in Western Europe. However, research results on eating habits and food choice in the Western Balkan Countries (WBCs) remain scarce. A Food Choice Questionnaire (FCQ), an instrument that measures the reported importance of nine factors underlying food choice, was administered to a representative sample of 3085 adult respondents in six WBCs. The most important factors reported are sensory appeal, purchase convenience, and health and natural content; the least important are ethical concern and familiarity. The ranking of food choice motives across WBCs was strikingly similar. Factor analysis revealed eight factors compared to nine in the original FCQ model: health and natural content scales loaded onto one factor as did familiarity and ethical concern; the convenience scale items generated two factors, one related to purchase convenience and the other to preparation convenience. Groups of consumers with similar motivational profiles were identified using cluster analysis. Each cluster has distinct food purchasing behavior and socio-economic characteristics, for which appropriate public health communication messages can be drawn. Copyright © 2011 Elsevier Ltd. All rights reserved.
-
The clinical course of diabetic nephropathy.
Kussman, M J; Goldstein, H; Gleason, R E
1976-10-18
A retrospective record analysis of 112 juvenile-onset diabetics with nephropathy was conducted in order to determine their clinical course. The mean duration of diabetes at the onset of proteinuria was 17.3+/-6.0 years. Early renal failure appeared two years after the onset of protein-uria, and severe renal failure (mean serum creatinine level, 8.5+/-3.9 mg/100 ml) four years after the onset of proteinuria. The mean duration of life after the onset of severe renal failure was six months. The mortality was 53%, with 59% of the deaths attributable to renal failure and 36% to cardiovascular disease. All patients experienced progressive deterioration of renal function as well as the other complications of diabetes, the rate of progression being accelerated toward the end of the course. Juvenile onset diabetics should be considered for renal transplantation before the serum creatinine level reaches 8.5 mg/100 ml.
-
Mycotic Infections Acquired outside Areas of Known Endemicity, United States
Thompson, George R.; Deresinski, Stan; Chiller, Tom
2015-01-01
In the United States, endemic mycoses—blastomycosis, coccidioidomycosis, and histoplasmosis—pose considerable clinical and public health challenges. Although the causative fungi typically exist within broadly defined geographic areas or ecologic niches, some evidence suggests that cases have occurred in humans and animals not exposed to these areas. We describe cases acquired outside regions of traditionally defined endemicity. These patients often have severe disease, but diagnosis may be delayed because of a low index of suspicion for mycotic disease, and many more cases probably go entirely undetected. Increased awareness of these diseases, with a specific focus on their potential occurrence in unusual areas, is needed. Continued interdisciplinary efforts to reevaluate and better describe areas of true endemicity are warranted, along with a more nuanced view of the notion of endemicity. The term “nonendemic” should be used with care; mycoses in such regions might more accurately be considered “not known to be endemic.” PMID:26485441
-
Diabetic nephropathy among Mexican Americans
Debnath, Subrata; Thameem, Farook; Alves, Tahira; Nolen, Jacqueline; Al-Shahrouri, Hania; Bansal, Shweta; Abboud, Hanna E.; Fanti, Paolo
2012-01-01
The incidence of diabetic nephropathy (DN) is growing rapidly worldwide as a consequence of the rising prevalence of Type 2 diabetes mellitus (T2DM). Among U.S. ethnic groups, Mexican Americans have a disproportionately high incidence and prevalence of DN and associated end-stage renal disease (ESRD). In communities bordering Mexico, as many as 90% of Mexican American patients with ESRD also suffer from T2DM compared to only 50% of non-Hispanic Whites (NHW). Both socio-economic factors and genetic predisposition appear to have a strong influence on this association. In addition, certain pathogenetic and clinical features of T2DM and DN are different in Mexican Americans compared to NHW, raising questions as to whether the diagnostic and treatment strategies that are standard practice in the NHW patient population may not be applicable in Mexican Americans. This article reviews the epidemiology of DN in Mexican Americans, describes the pathophysiology and associated risk factors, and identifies gaps in our knowledge and understanding that needs to be addressed by future investigations. PMID:22445478
-
Diabetic nephropathy among Mexican Americans.
Debnath, Subrata; Thameem, Farook; Alves, Tahira; Nolen, Jacqueline; Al-Shahrouri, Hania; Bansal, Shweta; Abboud, Hanna E; Fanti, Paolo
2012-04-01
The incidence of diabetic nephropathy (DN) is growing rapidly worldwide as a consequence of the rising prevalence of Type 2 diabetes mellitus (T2DM). Among U.S. ethnic groups, Mexican Americans have a disproportionately high incidence and prevalence of DN and associated end-stage renal disease (ESRD). In communities bordering Mexico, as many as 90% of Mexican American patients with ESRD also suffer from T2DM compared to only 50% of non-Hispanic Whites (NHW). Both socio-economic factors and genetic predisposition appear to have a strong influence on this association. In addition, certain pathogenetic and clinical features of T2DM and DN are different in Mexican Americans compared to NHW, raising questions as to whether the diagnostic and treatment strategies that are standard practice in the NHW patient population may not be applicable in Mexican Americans. This article reviews the epidemiology of DN in Mexican Americans, describes the pathophysiology and associated risk factors, and identifies gaps in our knowledge and understanding that needs to be addressed by future investigations.
-
Xiao, Chenggen; Zhou, Qiaoling; Li, Xiaozhao; Li, Hui; Zhong, Yong; Meng, Ting; Zhu, Mengyuan; Sun, Hong; Liu, Shuang; Tang, Rong; Pu, Jiaxi; Xu, Yan; Xiao, Ping
2017-01-01
Angiotensin II is considered a major profibrotic factor that is involved in tissue remodeling processes, as the inhibition of Angiotensin II can halt renal inflammatory processes. Dexamethasone, an important anti-inflammatory and immunosuppressive agent, has been widely used to treat renal disease for decades. In this study, we explored the frequency of Th22 cells in a mouse model of IgA nephropathy and compared the possible effects of Losartan and Dexamethasone on Th22 cells. The experiments were performed using 6-week-old BALB/c female mice in an established IgA nephropathy model. The mice were randomly separated into 4 groups, which were administered Losartan (30mg/kg/d) or Dexamethasone (10mg/kg/d) and subjected to IgA nephropathy or the normal control treatment for 1month. The frequency of Th22 cells was measured via flow cytometry, and the relative pathological changes in renal morphology were measured with different pathological staining methods. Immunohistochemistry was performed to verify the expression of CCR10 and CCL27, which is specialized receptor on Th22 cells and its corresponding chemokine, respectively. The concentrations of CCL27 and IL-22 in renal tissue homogenates and sera were detected using ELISAs. Losartan and Dexamethasone differentially decreased the frequency of Th22 cells after 1month, and mesangial cell proliferation was also improved. Moreover, the expression of CCR10, CCL27 and IL-22 was reduced by treatment with either drug. However, significant differences between Losartan and Dexamethasone were not observed. Based on these findings, Losartan and Dexamethasone may suppress inflammatory responses by inhibiting the chemotaxis of Th22 cells in IgA nephropathy. Copyright © 2016. Published by Elsevier B.V.
-
Liu, Kai; Xu, Huiqin; Lv, Gaohong; Liu, Bin; Lee, Maxwell Kim Kit; Lu, Chunhong; Lv, Xing; Wu, Yunhao
2015-02-15
Diabetic nephropathy is the most common cause of end-stage renal disease in patients with diabetes. Advanced glycation end-products (AGEs) play a prominent role in the development of diabetic nephropathy. We herein evaluated the effects of loganin on diabetic nephropathy in vivo. We established a diabetic nephropathy model in C57BL/6J mice with diabetes induced by streptozotocin and fed with diets containing high level of AGEs. Diabetic symptoms, renal functions, and pathohistology of pancreas and kidney were evaluated. AGE-RAGE pathway and oxidative stress parameters were determined. The model mice exhibited characteristic symptoms of diabetes including weight loss, polydipsia, polyphagia, polyuria, elevated blood glucose levels and low serum insulin levels during the experiments. However, loganin at doses of 0.02 and 0.1g/kg effectively improved these diabetic symptoms. Loganin reduced kidney/body weight ratio, 24h urine protein levels, and serum levels of urea nitrogen and creatinine in diabetic mice to different degrees compared to positive controls. Moreover, loganin improved the histology of pancreas and kidney, and alleviated the structural alterations in endothelial cells, mesangial cells and podocytes in renal cortex. Finally, we found that loganin reduced AGE levels in serum and kidney and downregulated mRNA and protein expression of receptors for AGEs in kidney in diabetic mice. Loganin also reduced the levels of malondialdehyde and increased the levels of superoxide dismutase in serum and kidney. Loganin improved diabetic nephropathy in vivo associated with inhibition of AGE pathways, and could be a promising remedy for diabetic nephropathy. Copyright © 2015 Elsevier Inc. All rights reserved.
-
Therapeutic Modalities in Diabetic Nephropathy: Future Approaches*
Reeves, William Brian; Rawal, Bishal B.; Abdel-Rahman, Emaad M.; Awad, Alaa S.
2012-01-01
Diabetes mellitus is the leading cause of end stage renal disease and is responsible for more than 40% of all cases in the United States. Several therapeutic interventions for the treatment of diabetic nephropathy have been developed and implemented over the past few decades with some degree of success. However, the renal protection provided by these therapeutic modalities is incomplete. More effective approaches are therefore urgently needed. Recently, several novel therapeutic strategies have been explored in treating DN patients including Islet cell transplant, Aldose reductase inhibitors, Sulodexide (GAC), Protein Kinase C (PKC) inhibitors, Connective tissue growth factor (CTGF) inhibitors, Transforming growth factor-beta (TGF-β) inhibitors and bardoxolone. The benefits and risks of these agents are still under investigation. This review aims to summarize the utility of these novel therapeutic approaches. PMID:23293752
-
Min, Lulin; Wang, Qin; Cao, Liou; Zhou, Wenyan; Yuan, Jiangzi; Zhang, Minfang; Che, Xiajing; Mou, Shan; Fang, Wei; Gu, Leyi; Zhu, Mingli; Wang, Ling; Yu, Zanzhe; Qian, Jiaqi; Ni, Zhaohui
2017-07-18
IgA nephropathy is the most common primary glomerulonephritis and one of the leading causes of end-stage renal disease. We performed a randomized, controlled, prospective, open-label trial to determine whether leflunomide combined with low-dose corticosteroid is safe and effective for the treatment of progressive IgA nephropathy, as compared to full-dose corticosteroid monotherapy. Biopsy-proved primary IgA nephropathy patients with an estimated glomerular filtration rate ≥ 30 ml/min/1.73m2 and proteinuria ≥1.0 g/24h were randomly assigned to receive leflunomide+low-dose corticosteroid (leflunomide group; n = 40) or full-dose corticosteroid (corticosteroids group; n = 45). The primary outcome was renal survival; secondary outcomes were proteinuria and adverse events. After 12 months of treatment and an average follow-up of 88 months, 11.1% vs. 7.5% of patients reached end-stage renal disease and 20% versus 10% of patients had a ≥ 50% increase in serum creatinine in the corticosteroids and leflunomide groups, respectively. Kaplan-Meier analysis did not reveal a between-group difference in these outcomes. Decreases in 24-hour proteinuria were similar in the two groups during the treatment period, but a more marked reduction was observed during follow-up in the leflunomide group. Although the incidence of adverse events was similar in the two groups, serious adverse events were observed only in the corticosteroid group. Thus, leflunomide combined with low-dose corticosteroid is at least as effective as corticosteroid alone for the treatment of progressive IgA nephropathy, and showed a greater reduction of proteinuria during long-term follow-up and fewer severe adverse events.
-
Heras Benito, M; Garrido Blázquez, M; Gómez Sanz, Y; Bernardez Mardomingo, M; Ruiz Cacho, J; Rodríguez Recio, F J; Fernández-Reyes Luis, M J
2018-05-17
To analyze the incidence of contrast-induced nephropathy in a cohort of patients undergoing computed tomography (CT) with intravenous iodinated contrast material. To evaluate the efficacy of N-acetylcysteine in preventing contrast-induced nephropathy. This prospective observational study was carried out in the months comprising March 2016 through July 2016. We selected the first five patients scheduled to undergo CT examination each day who agreed to participate and signed the informed consent form. We recorded patients' cardiovascular histories, chronic treatments, and indications for the CT examination. We measured blood levels of creatinine and urea before and after the CT examination. We used the Modification of Diet in Renal Disease (MDRD-4) equation to estimate the glomerular filtration rate. We analyzed the type and dose of contrast material. We recorded whether N-acetylcysteine was administered before the CT examination. We used SPSS 15.0 ® to compare means and proportions. Statistical significance was set at p < 0.05. No incidents of contrast-induced nephropathy were detected in any of the 202 patients included [mean age, 63.92 ± 12 years (range 22-87); 57.4% male; 21.8% diabetic; 39.6% hypertensive; 87.1% had MDRD4 ≥ 60 ml/min/1.73 m 2 (89.45 ± 14, range 62.36-134.14) and 12.9% had MDRD4 < 60 ml/min/1.73 m 2 (45.38 ± 11, range 9.16-58.90)]. The most common indication for CT examinations was oncologic (81.2%). The only contrast agent administered was iopamidol; the mean dose was 107.83 ± 11 ml (range 70-140). The mean interval between pre-CT and post-CT laboratory tests was 4.06 ± 1 days. Only 13 patients received N-acetylcysteine; 9 of these had MDRD < 60 ml/min/1.73 m 2 and 4 had MDRD4 ≥ 60 ml/min/1.73 m 2 (p = 0.000). The incidence of contrast-induced nephropathy was not significant in patients with glomerular filtration rates greater than 30 ml/min/1.73 m 2 : these favorable results might be due to
-
Nam, Soo Min; Lee, Mi Young; Koh, Jang Hyun; Park, Jun Ho; Shin, Jang Yel; Shin, Young Goo; Koh, Sang Baek; Lee, Eun Young; Chung, Choon Hee
2009-02-01
Diabetic nephropathy is the most serious complication in diabetes mellitus. Oxidative stress via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and vascular endothelial growth factor (VEGF) pathway play critical roles in the development of diabetic nephropathy. We evaluated the effects of apocynin, NADPH oxidase inhibitor on diabetic nephropathy in a type 2 diabetic rat model. Sixteen Otsuka Long Evans Tokushima Fatty (OLETF) rats and 9 Long Evans Tokushima Otsuka (LETO) were divided into the following three groups: LETO rats (n=9), control OLETF rats (n=7) and apocynin-treated OLETF rats (n=9). We examined body weights, plasma glucose levels, urinary albumin-creatinine ratio (ACR) and protein-creatinine ratio (PCR). At 50 weeks, experimental rats were sacrificed and their kidneys were extracted for hematoxylin eosin stain, immunohistochemical VEGF stain and VEGF mRNA real-time RT-PCR. To examine oxidative stress, we checked 24h urinary 8-OHdG (8-hydroxy-2'-deoxyguanosine) and MDA (malondialdehyde). Urinary protein and albumin excretions were reduced after apocynin treatment, though apocynin could not significantly decrease serum glucose levels. There were improvements of glomerular and mesangial expansion in the apocynin-treated OLETF rats. Apocynin significantly decreased optical density of glomerular VEGF expression in immunohistochemical stain and reduced the concentration of 24h urinary 8-OHdG and MDA. From these results, it was suggested that apocynin may have the potential to protect against diabetic nephropathy via amelioration of oxidative stress.
-
Faunistic diversity of spiders (Araneae) in Galichitsa mountain (FYR Macedonia)
2013-01-01
Abstract A total of 294 species from 31 families have been found in Galichitsa Mt. Of them, 85 species are new to the mountain, while 20 are also new to the fauna of FYR of Macedonia. According to their current distribution the established species can be assigned to 17 zoogeographical categories, grouped into 5 complexes (Cosmopolitan, Holarctic, European, Mediterranean, Endemics of Balkans). Dominant are Holarctic species (66.0%) followed by European (16.5%) and Mediterranean (9.3%). The endemics (6.2%) and Southeast European species (1.7%) emphasize the local character of this fauna, but its low percentage suggests an important process of colonization. PMID:24723771
-
Targeted deletion of kidney glucose-6 phosphatase leads to nephropathy
clar, julie; Gri, Blandine; Calderaro, Julien; Birling, Marie-Christine; Herault, Yann; Smith, Peter; Mithieux, Gilles; Rajas, Fabienne
2014-01-01
Renal failure is a major complication that arises with aging in glycogen storage disease type 1a and type 1b patients. In the kidneys, glucose-6 phosphatase catalytic subunit (encoded by G6pc) deficiency leads to the accumulation of glycogen; this effect results in marked nephromegaly and progressive glomerular hyperperfusion and hyperfiltration, which precede the development of microalbuminuria and proteinuria. To better understand the end-stage nephropathy in glycogen storage disease type 1a, we generated a novel kidney-specific G6pc knock-out (K-G6pc−/−) mouse, which exhibited normal life expectancy. After 6 months of G6pc deficiency, K-G6pc−/− mice showed glycogen overload leading to nephromegaly and tubular dilation. Moreover, renal accumulation of lipids due to activation of de novo lipogenesis was observed. This led to the activation of the renin-angiotensin system and the development of epithelial-mesenchymal transition process and podocyte injury via transforming growth factor β1 signaling. Thus, K-G6pc−/− mice developed microalbuminuria caused by the impairment of glomerular filtration barrier. In conclusion, renal G6pc deficiency alone is sufficient to induce the development of the early onset nephropathy observed in glycogen storage disease type 1a, independently of the liver disease. K-G6pc−/− mouse model is a unique tool to decipher the molecular mechanisms underlying renal failure and to evaluate potential therapeutic strategies. PMID:24717294
-
Prognosis and treatment of diabetic nephropathy: Recent advances and perspectives.
Rossing, Peter; Persson, Frederik; Frimodt-Møller, Marie
2018-04-01
Approximately 20 to 40% of patients with type 1 or type 2 diabetes develop diabetic kidney disease. It is a clinical syndrome characterized by persistent albuminuria (>300mg/24h, or 300mg/g creatinine), a relentless decline in glomerular filtration rate, raised arterial blood pressure and enhanced cardiovascular morbidity and mortality. The natural course of classical diabetic nephropathy is initially microalbuminuria or moderately increased urine albumin excretion (30-300mg/g creatinine). Untreated microalbuminuria may then rise gradually, reaching severely increased albuminuric (macroalbuminuria) over 5 to 15 years. Glomerular filtration rate then begins to decline and end-stage renal failure is reached without treatment in 5 to 7 years. Regular, systematic screening for diabetic kidney disease is needed to identify patients at risk for, or with presymptomatic stages of diabetic kidney disease. Multifactorial intervention targeting glucose, lipids and blood pressure including blockade of renin angiotensin system and lifestyle, has improved renal and cardiovascular prognosis and reduced mortality with 50%. Recent data suggest beneficial pleiotropic effects on renal endpoint with new glucose lowering agents. It is also being investigated if blocking aldosterone could be an option as a potential new treatment. Thus, although diabetic nephropathy remains a major burden, prognosis has improved and new options for further improvements are currently tested in phase 3 clinical renal outcome studies. Copyright © 2018 Association Société de néphrologie. Published by Elsevier Masson SAS. All rights reserved.
-
Jha, Jay C.; Gray, Stephen P.; Barit, David; Okabe, Jun; El-Osta, Assam; Namikoshi, Tamehachi; Thallas-Bonke, Vicki; Wingler, Kirstin; Szyndralewiez, Cedric; Heitz, Freddy; Touyz, Rhian M.; Cooper, Mark E.; Schmidt, Harald H.H.W.
2014-01-01
Diabetic nephropathy may occur, in part, as a result of intrarenal oxidative stress. NADPH oxidases comprise the only known dedicated reactive oxygen species (ROS)–forming enzyme family. In the rodent kidney, three isoforms of the catalytic subunit of NADPH oxidase are expressed (Nox1, Nox2, and Nox4). Here we show that Nox4 is the main source of renal ROS in a mouse model of diabetic nephropathy induced by streptozotocin administration in ApoE−/− mice. Deletion of Nox4, but not of Nox1, resulted in renal protection from glomerular injury as evidenced by attenuated albuminuria, preserved structure, reduced glomerular accumulation of extracellular matrix proteins, attenuated glomerular macrophage infiltration, and reduced renal expression of monocyte chemoattractant protein-1 and NF-κB in streptozotocin-induced diabetic ApoE−/− mice. Importantly, administration of the most specific Nox1/4 inhibitor, GKT137831, replicated these renoprotective effects of Nox4 deletion. In human podocytes, silencing of the Nox4 gene resulted in reduced production of ROS and downregulation of proinflammatory and profibrotic markers that are implicated in diabetic nephropathy. Collectively, these results identify Nox4 as a key source of ROS responsible for kidney injury in diabetes and provide proof of principle for an innovative small molecule approach to treat and/or prevent chronic kidney failure. PMID:24511132
-
Yuan, Mingxia; Tang, Rong; Zhou, Qiaoling; Liu, Kanghan; Xiao, Zhou; Pouranan, Veeraragoo
2013-05-01
To examine the expressions of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) in the kidney of rats with diabetic nephropathy before and after the treatment of Cordyceps sinensis, and to explore the mechanism of Cordyceps sinensis against hypoxia. The diabetes model was produced by intraperitoneal injection of 60 mg/kg streptozotocin, then the rats whose 24 h urine protein level was above 30 mg/d were thought to have suffered diabetic nephropathy. Thirty rats were randomly divided into a diabetic nephropathy group (DN group, n=15) and a Cordyceps sinensis group (CS group, n=15), and another 15 normal rats served as a normal control group (NC group, n=15). The CS group were intragastrically administered Cordyceps sinensis extract liquid [5.0 g/(kg.d)], the other groups were intragastrically administered drinking water of equal volume. Five rats in each group were killed after 2, 4, and 6 weeks. The 24 h urine protein excretion, urine β-N-acetyl glucosaminidase (NAGase) and serum creatinine were measured; the renal pathological changes were evaluated by HE and Masson staining; the mRNA and protein expressions of HIF-1α and VEGF were dectected by reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. Compared with the normal control group, the renal tubular vacuolar degeneration was obvious, and the glomerular mesangial matrix increased in the DN group. The 24 h urinary protein excretion, urine NAGase and serum creatinine also increased significantly (all P<0.05); the expressions of HIF-1α and VEGF in the renal tissue gradually increased with time, and the expression of HIF-1α was correlated with that of VEGF in the 2 groups (r=0.850, r=0.887, both P<0.05) . Compared with the DN group, the pathological changes were relieved, the 24 h urinary protein excretion, urine NAGase and serum creatinine level were decreased, and the expressions of HIF-1α and VEGF decreased in the CS group (all P<0.05), but
-
Spasovski, Goce; Busic, Mirela; Delmonico, Francis
2016-01-01
Due to the limited access to kidney transplantation (KTx) in developing countries, desperate patients have engaged in the purchase and sale of kidneys. In 2004, the World Health Assembly urged member states to protect the poor and vulnerable from being exploited through practices of illegal organ trafficking that had become widespread throughout the world. In 2008, the international transplant community convened a summit of transplant professionals, legal experts and ethicists to combat organ trafficking, transplant tourism and transplant commercialism that resulted in the Declaration of Istanbul (DOI). The South-Eastern Europe Health Network (SEEHN) represents a nine country multigovernmental collaboration on health systems. The Regional Health Development Centre on Organ Donation and Transplant Medicine (RHDC) was established in 2011 in Croatia to facilitate cooperation among south-eastern European countries to improve organ transplantation within the Balkan region. Since 2011, a collaboration between the RHDC, the Custodian Group of the DOI (DICG) and SEEHN professionals has enhanced strategic planning and definition of country-specific action plan priorities on organ donation and transplantation. Data of kidney transplantation provided in this report show a significant increase in transplantation activities in a 4-year period in Macedonia, Moldova, Bosnia and Hercegovina, Romania and Montenegro. The success of the donation and transplantation programmes was influenced by the engagement of key professionals and the establishment of organizational infrastructure with the implementation of an appropriate funding model. In conclusion, the DOI has provided an ethical framework for engagement of health professionals from south-eastern European countries. The newly established SEEHN RHDC as a technical coordinating body greatly contributed in building institutional capacity and strengthening regional collaboration between health authorities and professionals within
-
Spasovski, Goce; Busic, Mirela; Delmonico, Francis
2016-02-01
Due to the limited access to kidney transplantation (KTx) in developing countries, desperate patients have engaged in the purchase and sale of kidneys. In 2004, the World Health Assembly urged member states to protect the poor and vulnerable from being exploited through practices of illegal organ trafficking that had become widespread throughout the world. In 2008, the international transplant community convened a summit of transplant professionals, legal experts and ethicists to combat organ trafficking, transplant tourism and transplant commercialism that resulted in the Declaration of Istanbul (DOI). The South-Eastern Europe Health Network (SEEHN) represents a nine country multigovernmental collaboration on health systems. The Regional Health Development Centre on Organ Donation and Transplant Medicine (RHDC) was established in 2011 in Croatia to facilitate cooperation among south-eastern European countries to improve organ transplantation within the Balkan region. Since 2011, a collaboration between the RHDC, the Custodian Group of the DOI (DICG) and SEEHN professionals has enhanced strategic planning and definition of country-specific action plan priorities on organ donation and transplantation. Data of kidney transplantation provided in this report show a significant increase in transplantation activities in a 4-year period in Macedonia, Moldova, Bosnia and Hercegovina, Romania and Montenegro. The success of the donation and transplantation programmes was influenced by the engagement of key professionals and the establishment of organizational infrastructure with the implementation of an appropriate funding model. In conclusion, the DOI has provided an ethical framework for engagement of health professionals from south-eastern European countries. The newly established SEEHN RHDC as a technical coordinating body greatly contributed in building institutional capacity and strengthening regional collaboration between health authorities and professionals within
-
Wysocki, Jan; Ye, Minghao; Khattab, Ahmed M; Fogo, Agnes; Martin, Aline; David, Nicolae Valentin; Kanwar, Yashpal; Osborn, Mark; Batlle, Daniel
2017-06-01
Blockers of the renin-angiotensin system are effective in the treatment of experimental and clinical diabetic nephropathy. An approach different from blocking the formation or action of angiotensin II (1-8) that could also be effective involves fostering its degradation. Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that cleaves angiotensin II (1-8) to form angiotensin (1-7). Therefore, we examined the renal effects of murine recombinant ACE2 in mice with streptozotocin-induced diabetic nephropathy as well as that of amplification of circulating ACE2 using minicircle DNA delivery prior to induction of experimental diabetes. This delivery resulted in a long-term sustained and profound increase in serum ACE2 activity and enhanced ability to metabolize an acute angiotensin II (1-8) load. In mice with streptozotocin-induced diabetes pretreated with minicircle ACE2, ACE2 protein in plasma increased markedly and this was associated with a more than 100-fold increase in serum ACE2 activity. However, minicircle ACE2 did not result in changes in urinary ACE2 activity as compared to untreated diabetic mice. In both diabetic groups, glomerular filtration rate increased significantly and to the same extent as compared to non-diabetic controls. Albuminuria, glomerular mesangial expansion, glomerular cellularity, and glomerular size were all increased to a similar extent in minicircle ACE2-treated and untreated diabetic mice, as compared to non-diabetic controls. Recombinant mouse ACE2 given for 4 weeks by intraperitoneal daily injections in mice with streptozotocin-induced diabetic nephropathy also failed to improve albuminuria or kidney pathology. Thus, a profound augmentation of ACE2 confined to the circulation failed to ameliorate the glomerular lesions and hyperfiltration characteristic of early diabetic nephropathy. These findings emphasize the importance of targeting the kidney rather than the circulatory renin angiotensin system to combat diabetic
-
Chromosome aberration analysis in peripheral lymphocytes of Gulf War and Balkans War veterans.
Schröder, H; Heimers, A; Frentzel-Beyme, R; Schott, A; Hoffmann, W
2003-01-01
Chromosome aberrations and sister chromatid exchanges (SCEs) were determined in standard peripheral lymphocyte metaphase preparations of 13 British Gulf War veterans, two veterans of the recent war in the Balkans and one veteran of both wars. All 16 volunteers suspect exposures to depleted uranium (DU) while deployed at the two different theatres of war in 1990 and later on. The Bremen laboratory control served as a reference in this study. Compared with this control there was a statistically significant increase in the frequency of dicentric chromosomes (dic) and centric ring chromosomes (cR) in the veterans' group. indicating a previous exposure to ionising radiation. The statistically significant overdispersion of die and cR indicates non-uniform irradiation as would be expected after non-uniform exposure and/or exposure to radiation with a high linear energy transfer (LET). The frequency of SCEs was decreased when compared with the laboratory control.
-
Correlation between Tick Density and Pathogen Endemicity, New Hampshire
Walk, Seth T.; Xu, Guang; Stull, Jason W.
2009-01-01
To assess the endemicity of tick-borne pathogens in New Hampshire, we surveyed adult tick vectors. Pathogens were more prevalent in areas of high tick density, suggesting a correlation between tick establishment and pathogen endemicity. Infection rates in ticks correlated with disease frequency in humans. PMID:19331738
-
Arsenijević, Jovana; Schillberg, Erin; Ponthieu, Aurelie; Malvisi, Lucio; Ahmed, Waeil A Elrahman; Argenziano, Stefano; Zamatto, Federica; Burroughs, Simon; Severy, Natalie; Hebting, Christophe; de Vingne, Brice; Harries, Anthony D; Zachariah, Rony
2017-01-01
Pushed by ongoing conflicts and pulled by the desire for a better life, over one million migrants/refugees transited Balkan countries and arrived in Europe during 2015 and early 2016. To curb this influx, European countries instituted restrictive migration policies often characterized by building of razor-wire border fences and border closures. Among migrants/refugees who received mental health care in Serbia while travelling through Balkan countries to Northern Europe, we assessed the prevalence and patterns of violent events experienced including physical trauma. A mixed methods study among migrants/refugees attending mobile mental health clinics run by Médecins sans Frontières (MSF) between July 2015 and June 2016, in Serbia - a main transit hub to European countries. Clinics were conducted according to MSF guidelines by experienced psychologists who were supported by cultural mediators. The main outcome measures were violent events and associated physical trauma. Of 992 migrants/refugees attending MSF mental health clinics, the majority (72%) were from Syria and Afghanistan and included vulnerable groups (14%) such as unaccompanied minors and pregnant women. The most frequent mental health symptoms/signs were anxiety (29%) and adjustment reactions (26%). Of the 992 migrants/refugees, 270 (27%) had experienced violent events during their journey. Signs of physical trauma due to acts of violence were seen in 223(22%) of the 992 individuals, 144 (65%) being perpetrated by State authorities and involving women (11%) and children (13%). Border closures along the Balkan route were associated with a dramatic decrease in registered migrants/refugee arrivals in Serbia. Conversely, among those that made it across the borders, an increasing linear trend in reported violent events was observed at MSF mental health clinics ( X 2 for linear trend, P <0 · 001). Qualitative evidence corroborated with quantitative findings. Nearly one-in-three migrants/refugees seen in
-
Umayahara, Yutaka; Fujita, Yohei; Watanabe, Hirotaka; Kasai, Noriko; Fujiki, Noritaka; Hatazaki, Masahiro; Koga, Masafumi
2017-04-01
The ratio of glycated albumin to HbA1c (GA/HbA1c ratio) is a known indicator that reflects fluctuations in plasma glucose. In this study, the association of the GA/HbA1c ratio to diabetic nephropathy and diabetic retinopathy in patients with type 2 diabetes was investigated. Among patients with type 2 diabetes, 613 patients (364 males and 249 females, aged 63.2±12.5, body mass index (BMI) 25.4±4.8kg/m 2 ) were enrolled. Patients with overt proteinuria, reduced renal function, or anemia were excluded. In a comparison between patients with and without diabetic nephropathy, significance was observed in insulin therapy, HbA1c, and GA. In addition, in a comparison between patients with and without diabetic retinopathy, the GA/HbA1c ratio along with insulin therapy, HbA1c, and GA showed significant differences. When the GA/HbA1c ratios were divided into three groups and compared, the rates of diabetic nephropathy did not show any significance, while the rate of diabetic retinopathy increased significantly as the GA/HbA1c ratio increased. In multivariable analyses, while insulin therapy and BMI were the significant independent variables for diabetic nephropathy, insulin therapy and the GA/HbA1c ratios were the significant independent variable for diabetic retinopathy. The GA/HbA1c ratio was associated with diabetic retinopathy, but not with diabetic nephropathy in patients with type 2 diabetes. These results suggest that the development and progression of diabetic retinopathy is associated with plasma glucose fluctuations. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.
-
Albumin Antioxidant Response to Stress in Diabetic Nephropathy Progression
Medina-Navarro, Rafael; Corona-Candelas, Itzia; Barajas-González, Saúl; Díaz-Flores, Margarita; Durán-Reyes, Genoveva
2014-01-01
Background A new component of the protein antioxidant capacity, designated Response Surplus (RS), was recently described. A major feature of this component is the close relationship between protein antioxidant capacity and molecular structure. Oxidative stress is associated with renal dysfunction in patients with renal failure, and plasma albumin is the target of massive oxidation in nephrotic syndrome and diabetic nephropathy. The aim of the present study was to explore the albumin redox state and the RS component of human albumin isolated from diabetic patients with progressive renal damage. Methods/Principal Findings Serum aliquots were collected and albumin isolated from 125 diabetic patients divided into 5 groups according to their estimated glomerular filtration rate (GFR). In addition to clinical and biochemical variables, the albumin redox state, including antioxidant capacity, thiol group content, and RS component, were evaluated. The albumin antioxidant capacity and thiol group content were reciprocally related to the RS component in association with GFR reduction. The GFR decline and RS component were significantly negatively correlated (R = –0.83, p<0.0001). Age, creatinine, thiol groups, and antioxidant capacity were also significantly related to the GFR decline (R = –0.47, p<0.001; R = –0.68, p<0.0001; R = 0.44, p<0.001; and R = 0.72, p<0.0001). Conclusion/Significance The response of human albumin to stress in relation to the progression of diabetic renal disease was evaluated. The findings confirm that the albumin molecular structure is closely related to its redox state, and is a key factor in the progression of diabetes nephropathy. PMID:25187963
-
USDA-ARS?s Scientific Manuscript database
This is the first report of the invasive rice pest, rice water weevil (Lissorhoptrus oryzophilus Kuschel) in the Balkans. Adult specimens were collected in flooded rice fields in the principal rice-growing region of Central Macedonia, Greece during July-August, 2016. Morphological identification was...
-
Vázquez García, M J; Vargas Camaño, M E; Olalde Carmona, R
2000-01-01
Systemic Lupus Eritematosus is an autoimmune disease, the incidence in pediatric poblation in about 5%, and until 90% develop nephropathy. Included patients with lupic nephropathy grade IV (OMS) ages between 0 and 16 years old, multitreated, who administrated PTX. We take samples before treatment, during, and 4 month after, evaluating renal function and hepatic function. For female, tow male, promedium age 14.1 years old. Poteinuria get a significative p = 0.0012; hematuria was lowering its levels, While immune circulating complex, get too a significative p = 0.0050. In creatinine inverse showed an important modification of its pending. This results demonstrates, that PTX in nephritis lupic patients, helps to brake the habitual deterioration in renal function. Includes more patients for a long time of treatment, we'll get better results than this.
-
Dubois, Adélaïde; Castel, Guillaume; Murri, Séverine; Pulido, Coralie; Pons, Jean-Baptiste; Benoit, Laure; Loiseau, Anne; Lakhdar, Latifa; Galan, Maxime; Charbonnel, Nathalie; Marianneau, Philippe
2017-05-02
In Europe, the occurrence of nephropathia epidemica (NE), a human disease caused by Puumala virus (PUUV), exhibits considerable geographical heterogeneity despite the continuous distribution of its reservoir, the bank vole Myodes glareolus. To better understand the causes of this heterogeneity, wild voles sampled in two adjacent NE endemic and non-endemic regions of France were infected experimentally with PUUV. The responses of bank voles to PUUV infection, based on the levels of anti-PUUV IgG and viral RNA, were compared. Slight regional differences were highlighted despite the high inter-individual variability. Voles from the NE non-endemic region showed greater immune responsiveness to PUUV infection, but lower levels of RNA in their organs than voles from the endemic region. These results suggest the existence of regional variations in the sensitivity of bank voles that could contribute to the apparent absence of PUUV circulation among voles and the absence of NE in the non-endemic region. Copyright © 2017 Elsevier B.V. All rights reserved.
-
[Safety threshold of fluorine in endemic fluorosis regions in China].
Li, Yonghua; Wang, Wuyi; Hou, Shaofan
2002-07-01
Four endemic fluorosis regions in China and their environmental epidemiological characteristics were summarized in this paper. It shows that the epidemiology of endemic fluorosis is closely related to geochemical parameters of local environment. The food-web and dose-effect relationship of fluoride from environment to human body in different types of endemic fluorosis regions were studied. And the safety threshold of fluoride in different regions was determined. The results have provided a scientific basis for environmental risk assessment of fluoride in China.
-
Characterization of diabetic nephropathy in CaM kinase IIalpha (Thr286Asp) transgenic mice.
Suzuki, Hikari; Kato, Ichiro; Usui, Isao; Takasaki, Ichiro; Tabuchi, Yoshiaki; Oya, Takeshi; Tsuneyama, Koichi; Kawaguchi, Hiroshi; Hiraga, Koichi; Takasawa, Shin; Okamoto, Hiroshi; Tobe, Kazuyuki; Sasahara, Masakiyo
2009-01-30
Detailed studies were performed on diabetic kidneys derived from transgenic mice overexpressing the mutant form (Thr286Asp) of Ca(2+)/calmodulin-dependent protein kinase IIalpha (CaM kinase IIalpha) in pancreatic beta-cells. Kidney weight/body weight ratio, urinary albumin/creatinine ratio, serum BUN level, and mesangial/glomerular area ratio were all significantly higher in transgenic mice than in wild-type mice. cDNA microarray analysis revealed 17 up-regulated genes and 12 down-regulated genes in transgenic kidney. Among up-regulated genes, cyclin D2 (6.70-fold) and osteopontin (2.35-fold) were thought to play important roles in the progression of diabetic nephropathy. Transgenic glomeruli and tubular epithelial cells were strongly stained for osteopontin, a molecule which induces immune response. In quantitative real-time RT-PCR analyses, expressions of not only M1 macrophage marker genes but also M2 macrophage marker genes were elevated in renal cortex of transgenic mice. Overall results indicate that CaM kinase IIalpha (Thr286Asp) transgenic mice serve as an excellent model for diabetic nephropathy.
-
Laroussi, L; Triki, M; Ibn Elhaj, Z; Ben Halima, A; Boukhris, M; Ben Amara, W; Keskes, H; Kraiem, S; Lahidheb, D; Marrakchi, S; Kammoun, I; Addad, F; Kachboura, S
2017-09-01
Contrast-induced nephropathy (CIN) is a common and severe complication in interventional cardiology. The aim of our study was to compare the incidence of contrast-induced nephropathy in two accelerated hydration protocols: the first one by the serum bicarbonate and the second combining the serum bicarbonate and oral vitamin C. This is a multicenter prospective, randomized study conducted between October 2012 and May 2013, including 160 patients. The mean age of our study population was 60.8±9.3 years (36-83 years). The two study groups were comparable in terms of cardiovascular risk factors, concomitant medication, and baseline serum creatinine. The CIN incidence was 6.3% in the vitamin C group and 10% in the control group (P=0.38). No significant difference was observed in terms of CIN incidence between the different subgroups analyzed. According to our study, ascorbic acid administered orally as part of an accelerated hydration protocol does not reduce the incidence of CIN. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
-
Zheng, Jing; Inoguchi, Toyoshi; Sasaki, Shuji; Maeda, Yasutaka; McCarty, Mark F; Fujii, Masakazu; Ikeda, Noriko; Kobayashi, Kunihisa; Sonoda, Noriyuki; Takayanagi, Ryoichi
2013-01-15
We and other investigators have reported that bilirubin and its precursor biliverdin may have beneficial effects on diabetic vascular complications, including nephropathy, via its antioxidant effects. Here, we investigated whether phycocyanin derived from Spirulina platensis, a blue-green algae, and its chromophore phycocyanobilin, which has a chemical structure similar to that of biliverdin, protect against oxidative stress and renal dysfunction in db/db mice, a rodent model for Type 2 diabetes. Oral administration of phycocyanin (300 mg/kg) for 10 wk protected against albuminuria and renal mesangial expansion in db/db mice, and normalized tumor growth factor-β and fibronectin expression. Phycocyanin also normalized urinary and renal oxidative stress markers and the expression of NAD(P)H oxidase components. Similar antioxidant effects were observed following oral administration of phycocyanobilin (15 mg/kg) for 2 wk. Phycocyanobilin, bilirubin, and biliverdin also inhibited NADPH dependent superoxide production in cultured renal mesangial cells. In conclusion, oral administration of phycocyanin and phycocyanobilin may offer a novel and feasible therapeutic approach for preventing diabetic nephropathy.
-
Zhang, Mianzhi; Liu, Miao; Xiong, Min; Gong, Junbo; Tan, Xiaoyue
2012-05-07
Schisandra chinensis fruit is widely used in Chinese medicine for the treatment of hepatic, renal, heart, cerebrovascular and infectious diseases. To investigate the effects of Schisandra chinensis fruit extract (SE) on albuminuria and podocyte injury as well as the underlying mechanism in the mouse model of streptozotocin (STZ)-induced diabetic nephropathy and in cultured mouse podocyte cells. SE was orally administrated in STZ-induced diabetic nephropathy mice for 7 weeks, at a daily dose of 5g/kg body weight. The urinary albumin/creatinine ratio and urine albumin excretion rate were measured at the 6th and 9th week of the experiment. The extent of glomerulosclerosis and extracellular matrix deposition were determined by periodic acid-silver methenamine and Masson's trichrome staining. The amount of podocytes and the integrity of the slit diaphragm were detected by immunohistological staining of podocyte markers, Wilms' tumor 1 and nephrin. Alpha-smooth muscle actin, E-cadherin and plasminogen activator inhibitor-1 were measured by western blot and immunohistological staining to evaluate the level of epithelial-to-mesenchymal transition (EMT). Real-time reverse transcription PCR was used to detect the mRNA level of E-cadherin, alpha-SMA and snail in cultured podocyte cells. Treatment with SE significantly decreased the urine albumin excretion rate and urinary albumin/creatinine ratio. In addition, SE attenuated glomerulosclerosis and protected against podocyte loss and integrity of the slit diaphragm. Furthermore, SE effectively prevented the EMT of podocytes caused by diabetic nephropathy. Our studies suggest that SE might be beneficial for diabetic nephropathy. The effects of SE on attenuating albuminuria and glomerulosclerosis are possibly mediated by preserving podocyte integrity through suppressing EMT. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
-
Wadén, Johan; Tikkanen, Heidi K; Forsblom, Carol; Harjutsalo, Valma; Thorn, Lena M; Saraheimo, Markku; Tolonen, Nina; Rosengård-Bärlund, Milla; Gordin, Daniel; Tikkanen, Heikki O; Groop, Per-Henrik
2015-05-01
The aim of this study was to assess how physical activity predicts the development and progression of diabetic nephropathy in patients with type 1 diabetes. This prospective study (follow-up time 6.4 ± 3.1 years) included 1,390 patients (48.5% men, mean age 37.0 ± 12.4 years, duration of diabetes 20.4 ± 12.3 years) participating in the nationwide multicentre Finnish Diabetic Nephropathy (FinnDiane) Study. Leisure-time physical activity (LTPA) was assessed using a validated self-report questionnaire. Renal status was defined according to standard clinical cut-off values for urinary AER. The total amount of LTPA was not associated with progression in renal status. For the intensity of LTPA, however, the 10 year cumulative progression rate was 24.0% (95% CI 18.8, 28.8), 13.5% (95% CI 10.3, 16.6) or 13.1% (95% CI 10.3%, 16.6%; p = 0.01) of the patients with low, moderate or high intensity LTPA. This pattern was similar to that for the development of de novo microalbuminuria. Corresponding progression rates for LTPA frequency of <1, 1-2 or >2 sessions/week was 24.7% (95% CI 18.3, 30.7), 14.7% (95% CI 10.2, 19.0) or 12.6% (95% CI 9.4, 15.7), respectively (p = 0.003). This study demonstrates for the first time in a prospective setting the relationship between physical activity and the risk of diabetic nephropathy in patients with type 1 diabetes. The data suggest that physical activity, and in particular its intensity, may have an impact on the initiation and progression of diabetic nephropathy in type 1 diabetes.
-
DOE Office of Scientific and Technical Information (OSTI.GOV)
Qian, Xin; Li, Xinghui; Ma, Fenfen
2016-05-13
In this work, we demonstrated for the first time that S-propargyl-cysteine (SPRC, also named as ZYZ-802), a novel hydrogen sulfide (H{sub 2}S)-releasing compound, had renoprotective effects on streptozotocin (STZ)-induced diabetic kidney injury. SPRC treatment significantly reduced the level of creatinine, kidney to body weight ratio and in particular, markedly decreased 24-h urine microalbuminuria excretion. SPRC suppressed the mRNA expression of fibronectin and type IV collagen. In vitro, SPRC inhibited mesangial cells over-proliferation and hypertrophy induced by high glucose. Additionally, SPRC attenuated inflammation in diabetic kidneys. SPRC also reduced transforming growth factor β1 (TGF-β1) signaling and expression of phosphorylated Smad3 (p-Smad3) pathway. Moreover,more » SPRC inhibited phosphorylation of ERK, p38 protein. Taken together, SPRC was demonstrated to be a potential therapeutic candidate to suppress diabetic nephropathy. - Highlights: • We synthesized a novel hydrogen sulfide-releasing compound, S-propargyl-cysteine (SPRC). • SPRC was preliminarily demonstrated to prevent STZ-induced diabetic nephropathy (DN). • SPRC may exert potential therapeutic candidate to suppress DN.« less
-
[Lupus nephropathy in black patients with systemic lupus erythematosus in Senegal: 43 cases].
Ka, E F; Cisse, M M; Lemrabott, A T; Fall, S; Diallo, M; Diallo, S; Faye, M; Niang, A; Diouf, B
2013-01-01
This study sought to assess the prevalence of lupus nephropathy and to determine its clinical, histological, therapeutic and outcome profiles. This retrospective study examined records covering a 10-year period from 1999 to 2009 at the nephrology department of the Aristide Le Dantec University Hospital Center. The records showed 43 patients with systemic lupus erythematosus (SLE), and 72% had lupus nephritis. The patients' mean age was 32.9 years; 40 were women and 3 men, for a sex ratio of 0.075. The lupus nephritis led to discovery of SLE in 27.9%. The mean proteinuria concentration was 2.01 g/dL. Seventeen patients had impaired renal function, and 26 had renal biopsies. It found class II nephritis in 2 patients, class IV in 10, and class V in 12. In addition, fifteen patients received combined corticosteroid + immunosuppressant treatment. Four patients died during the study period, one from SLE activity, two from complications of renal failure, and the fourth from sepsis. A larger study would be useful to assess more acurately the prevalence of various classes and severity of lupus nephropathy among blacks living in sub-Saharan Africa.
-
A Preliminary Mycological Investigation of Endemic Nephropathy in Yugoslavia,
FUNGI , *FOOD, *MOLDS(ORGANISMS), DISEASES, KIDNEYS, CORN, CEREALS, PORK, BIOLOGICAL CONTAMINATION, EPIDEMIOLOGY, DIAGNOSIS(MEDICINE), CORRELATION TECHNIQUES, INFECTIOUS DISEASES, ETIOLOGY, POPULATION, YUGOSLAVIA.
-
Yamamoto, Junichiro; Sato, Waichi; Kosugi, Tomoki; Yamamoto, Tokunori; Kimura, Toshihide; Taniguchi, Shigeki; Kojima, Hiroshi; Maruyama, Shoichi; Imai, Enyu; Matsuo, Seiichi; Yuzawa, Yukio; Niki, Ichiro
2013-02-01
Hydrogen sulfide (H(2)S) has recently been found to play beneficial roles in ameliorating several diseases, including hypertension, atherosclerosis and cardiac/renal ischemia-reperfusion injuries. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), the main enzymes in the transsulfuration pathway, catalyze H(2)S production in mammalian tissues. However, the distributions and precise roles of these enzymes in the kidney have not yet been identified. The present study examined the localization of both enzymes in the normal kidney and the effect of the H(2)S donor sodium hydrosulfide (NaHS) in the renal peritubular capillary (PTC) under conditions of diabetic nephropathy, using pancreatic β-cell-specific calmodulin-overexpressing transgenic mice as a model of diabetes. In the normal kidney, we detected expression of both CBS and CSE in the brush border and cytoplasm of the proximal tubules, but not in the glomeruli, distal tubules and vascular endothelial cells of renal PTCs. Administration of NaHS increased PTC diameter and blood flow. We further evaluated whether biosynthesis of H(2)S was altered in a spontaneous diabetic model that developed renal lesions similar to human diabetic nephropathy. CSE expression was markedly reduced under diabetic conditions, whereas CBS expression was unaffected. Progressive diabetic nephropathy showed vasoconstriction and a loss of blood flow in PTCs that was ameliorated by NaHS treatment. These findings suggest that CSE expression in the proximal tubules may also regulate tubulointerstitial microcirculation via H(2)S production. H(2)S may represent a target of treatment to prevent progression of ischemic injury in diabetic nephropathy.
-
Coccidioidomycosis and other endemic mycoses in Mexico.
Laniado-Laborín, Rafael
2007-12-31
The endemic mycoses traditionally include coccidioidomycosis, histoplasmosis, blastomycosis and paracoccidioidomycosis. Although sporotrichosis and chromomycosis are technically not included among the endemic mycoses, they are frequently diagnosed in Mexico. Most systemic endemic mycoses are a consequence of inhaling the fungi, while subcutaneous mycoses are acquired through the inoculation of vegetable matter or soil containing the organism. Coccidioidomycosis is caused by Coccidioides spp., a dimorphic pathogenic fungus. Approximately 60% of exposures result in asymptomatic infection; in the rest there are protean manifestations that range from a benign syndrome also known as "Valley Fever" to progressive pulmonary or extrapulmonary disease. Histoplasmosis, caused by the dimorphic fungus Histoplasma capsulatum, is endemic to the Americas. Pulmonary histoplasmosis manifestations are protean, ranging from a brief period of malaise to a severe, prolonged illness. The spectrum of illness in disseminated histoplasmosis ranges from a chronic, intermittent course to an acute and rapidly fatal infection. Paracoccidioidomycosis is a chronic, granulomatous systemic disease caused by Paracoccidioides brasiliensis that characteristically produces a primary pulmonary infection, often asymptomatic, and then disseminates to form ulcerative granulomata of the oral, nasal and occasionally the gastrointestinal mucosa. Sporotrichosis, caused by Sporothrix schenckii, has diverse clinical manifestations; the most frequent is the lymphocutaneous form. Generally, infection results from inoculation of the fungus through thorns, splinters, scratches and small traumas. Chromomycosis (Chromoblastomycosis) is a slowly progressive cutaneous and subcutaneous mycosis attributed to various saprophyte Hypomycetes fungi. The primary lesion is also thought to develop as a result of percutaneous traumatic inoculation.
-
On depleted uranium: gulf war and Balkan syndrome.
Duraković, A
2001-04-01
The complex clinical symptomatology of chronic illnesses, commonly described as Gulf War Syndrome, remains a poorly understood disease entity with diversified theories of its etiology and pathogenesis. Several causative factors have been postulated, with a particular emphasis on low level chemical warfare agents, oil fires, multiple vaccines, desert sand (Al-Eskan disease), botulism, Aspergillus flavus, Mycoplasma, aflatoxins, and others, contributing to the broad scope of clinical manifestations. Among several hundred thousand veterans deployed in the Operation Desert Storm, 15-20% have reported sick and about 25,000 died. Depleted uranium (DU), a low-level radioactive waste product of the enrichment of natural uranium with U-235 for the reactor fuel or nuclear weapons, has been considered a possible causative agent in the genesis of Gulf War Syndrome. It was used in the Gulf and Balkan wars as an armor-penetrating ammunition. In the operation Desert Storm, over 350 metric tons of DU was used, with an estimate of 3-6 million grams released in the atmosphere. Internal contamination with inhaled DU has been demonstrated by the elevated excretion of uranium isotopes in the urine of the exposed veterans 10 years after the Gulf war and causes concern because of its chemical and radiological toxicity and mutagenic and carcinogenic properties. Polarized views of different interest groups maintain an area of sustained controversy more in the environment of the public media than in the scientific community, partly for the reason of being less than sufficiently addressed by a meaningful objective interdisciplinary research.
-
Endemic and widespread coral reef fishes have similar mitochondrial genetic diversity.
Delrieu-Trottin, Erwan; Maynard, Jeffrey; Planes, Serge
2014-12-22
Endemic species are frequently assumed to have lower genetic diversity than species with large distributions, even if closely related. This assumption is based on research from the terrestrial environment and theoretical evolutionary modelling. We test this assumption in the marine environment by analysing the mitochondrial genetic diversity of 33 coral reef fish species from five families sampled from Pacific Ocean archipelagos. Surprisingly, haplotype and nucleotide diversity did not differ significantly between endemic and widespread species. The probable explanation is that the effective population size of some widespread fishes locally is similar to that of many of the endemics. Connectivity across parts of the distribution of the widespread species is probably low, so widespread species can operate like endemics at the extreme or isolated parts of their range. Mitochondrial genetic diversity of many endemic reef fish species may not either limit range size or be a source of vulnerability. © 2014 The Author(s) Published by the Royal Society. All rights reserved.
-
Rim, Tyler Hyung Taek; Byun, Il Hwan; Kim, Han Sang; Lee, Sang Yeul; Yoon, Jin Sook
2013-06-01
This cross-sectional study was done to identify and determine the socio-demographic and health-related factors associated with diabetic retinopathy and nephropathy screening in Korea. Participants included 2,660 adults, aged 40 or older, with diabetes. Of the 2,660 adults, 998 (37%) and 1,226 (46.1%) had received a diabetic retinopathy and a nephropathy screening within one year, respectively. Regarding retinopathy, subjects older than 65, living in urban areas, with high educational levels, and with self-reported "unhealthy" status were likely to receive annual screening. Subjects living in urban areas, with higher educational levels, with self-reported "fair" or "unhealthy" status, and with 1 to 2 co-morbidities were likely to receive annual nephropathy screening. The Korea Composite Stock Price Index (KOSPI) continued to rise until 2007 when it started to decline over the subsequent years, following the same curve as the diabetic retinopathy and nephropathy screening rates during that time. Together with the financial matter, lack of patient education proved to be a hindrance to diabetes-related screening. The relatively low screening rates in Korea compared to the Western countries are likely to be due to the difference in the health system, economic situations and national demographics.
-
Nikolaidis, George; Petroulaki, Kiki; Zarokosta, Foteini; Tsirigoti, Antonia; Hazizaj, Altin; Cenko, Enila; Brkic-Smigoc, Jelena; Vajzovic, Emir; Stancheva, Vaska; Chincheva, Stefka; Ajdukovic, Marina; Rajter, Miro; Raleva, Marija; Trpcevska, Liljana; Roth, Maria; Antal, Imola; Ispanovic, Veronika; Hanak, Natasha; Olmezoglu-Sofuoglu, Zeynep; Umit-Bal, Ismail; Bianchi, Donata; Meinck, Franziska; Browne, Kevin
2018-01-01
Children's exposure to violence is a major public health issue. The Balkan epidemiological study on Child Abuse and Neglect project aimed to collect internationally comparable data on violence exposures in childhood. A three stage stratified random sample of 42,194 school-attending children (response rate: 66.7%) in three grades (aged 11, 13 and 16 years) was drawn from schools in Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Former Yugoslavian Republic of Macedonia (FYROM), Greece, Romania, Serbia and Turkey. Children completed the ICAST-C questionnaire, which measures children's exposure to violence by any perpetrator. Exposure rates for psychological violence were between 64.6% (FYROM) and 83.2% (Greece) for lifetime and 59.62% (Serbia) and 70.0% (Greece) for past-year prevalence. Physical violence exposure varied between 50.6% (FYROM) and 76.3% (Greece) for lifetime and 42.5% (FYROM) and 51.0% (Bosnia) for past-year prevalence. Sexual violence figures were highest for lifetime prevalence in Bosnia (18.6%) and lowest in FYROM (7.6%). Lifetime contact sexual violence was highest in Bosnia (9.8%) and lowest in Romania (3.6%). Past-year sexual violence and contact sexual violence prevalence was lowest in Romania (5.0 and 2.1%) and highest in Bosnia (13.6 and 7.7% respectively). Self-reported neglect was highest for both past-year and lifetime prevalence in Bosnia (48.0 and 20.3%) and lowest in Romania (22.6 and 16.7%). Experiences of positive parental practices were reported by most participating children in all countries. Where significant differences in violence exposure by sex were observed, males reported higher exposure to past-year and lifetime sexual violence and females higher exposure to neglect. Children in Balkan countries experience a high burden of violence victimization and national-level programming and child protection policy making is urgently needed to address this.
-
NASA Astrophysics Data System (ADS)
Van Hinsbergen, D. J. J.; Maffione, M.
2017-12-01
Jurassic subduction initiation in the Neo-Tethys Ocean was the first, critical step of a long tectonic process that eventually led to the collision of the Adria-Africa and Eurasia plates and the formation of a 6000 km long Alpine orogenic belt spanning from the Balkan Peninsula to Iran. Investigating the process of subduction initiation in the Neo-Tethys during the Jurassic is crucial to (i) reconstruct the complex geological evolution of this orogen from its initial stages, and (ii) shed new lights over the enigmatic kinematics and driving mechanisms of subduction initiation. Records of the initial closure of the Neo-Tethys are today preserved in a fragmented belt of Middle Jurassic ophiolites (170-160 Ma) distributed above the Alpine orogen. In particular, the well-preserved and extensively studied ophiolites of the Balkan Peninsula offer a unique chance to study the mechanisms leading to the closure of the western domain of the Neo-Tethys. Here we provide the first quantitative constraints on the geometry of the Jurassic Neo-Tethyan subduction system using a net tectonic rotation analysis based on paleomagnetic and structural geological data from the sheeted dyke complexes of various ophiolites of Serbia (Maljen, Ibar) and Greece (Othris, Pindos, Vourinos, Guevgueli). Our results show that closure of the western Neo-Tethys was accommodated by two subduction zones, one intra-oceanic, formed at the N-S trending Neo-Tethyan ridge, the other initiated at the European passive margin and curving southward from a N-S to a NW-SE direction following the shape of the passive margin. We propose that these two subduction zones formed upon propagation of subduction(s) initiated in the central Neo-Tethys (modern Turkey) in the late Early Jurassic ( 185-180 Ma).
-
Lv, Jicheng; Zhang, Hong; Wong, Muh Geot; Jardine, Meg J; Hladunewich, Michelle; Jha, Vivek; Monaghan, Helen; Zhao, Minghui; Barbour, Sean; Reich, Heather; Cattran, Daniel; Glassock, Richard; Levin, Adeera; Wheeler, David; Woodward, Mark; Billot, Laurent; Chan, Tak Mao; Liu, Zhi-Hong; Johnson, David W; Cass, Alan; Feehally, John; Floege, Jürgen; Remuzzi, Giuseppe; Wu, Yangfeng; Agarwal, Rajiv; Wang, Hai-Yan; Perkovic, Vlado
2017-08-01
Guidelines recommend corticosteroids in patients with IgA nephropathy and persistent proteinuria, but the effects remain uncertain. To evaluate the efficacy and safety of corticosteroids in patients with IgA nephropathy at risk of progression. The Therapeutic Evaluation of Steroids in IgA Nephropathy Global (TESTING) study was a multicenter, double-blind, randomized clinical trial designed to recruit 750 participants with IgA nephropathy (proteinuria greater than 1 g/d and estimated glomerular filtration rate [eGFR] of 20 to 120 mL/min/1.73 m2 after at least 3 months of blood pressure control with renin-angiotensin system blockade] and to provide follow-up until 335 primary outcomes occurred. Patients were randomized 1:1 to oral methylprednisolone (0.6-0.8 mg/kg/d; maximum, 48 mg/d) (n = 136) or matching placebo (n = 126) for 2 months, with subsequent weaning over 4 to 6 months. The primary composite outcome was end-stage kidney disease, death due to kidney failure, or a 40% decrease in eGFR. Predefined safety outcomes were serious infection, new diabetes, gastrointestinal hemorrhage, fracture/osteonecrosis, and cardiovascular events. The mean required follow-up was estimated to be 5 years. After randomization of 262 participants (mean age, 38.6 [SD, 11.1] years; 96 [37%] women; eGFR, 59.4 mL/min/1.73 m2; urine protein excretion, 2.40 g/d) and 2.1 years' median follow-up, recruitment was discontinued because of excess serious adverse events. Serious events occurred in 20 participants (14.7%) in the methylprednisolone group vs 4 (3.2%) in the placebo group (P = .001; risk difference, 11.5% [95% CI, 4.8%-18.2%]), mostly due to excess serious infections (11 [8.1%] vs 0; risk difference, 8.1% [95% CI, 3.5%-13.9%]; P < .001), including 2 deaths. The primary renal outcome occurred in 8 participants (5.9%) in the methylprednisolone group vs 20 (15.9%) in the placebo group (hazard ratio, 0.37 [95% CI, 0.17-0.85]; risk difference, 10.0% [95% CI, 2
-
Effects of mineralocorticoid receptor antagonists on the progression of diabetic nephropathy.
Sun, Li-Jing; Sun, Yan-Ni; Shan, Jian-Ping; Jiang, Geng-Ru
2017-07-01
We aimed to evaluate the potential benefits and adverse effects of adding a mineralocorticoid receptor antagonist (MRA) to angiotensin-converting enzyme inhibitors (ACEI) and/or angiotensin receptor blockers (ARB), as standard treatment in patients with diabetic nephropathy. We scanned the Embase, PubMed and Cochrane Central Register of Controlled Trials databases for human clinical trials published in English until June 2016, evaluating renal outcomes in patients with diabetic nephropathy. A total of 18 randomized controlled trials involving 1,786 patients were included. Compared with ACEI/ARB alone, co-administration of MRA and ACEI/ARB significantly reduced urinary albumin excretion and the urinary albumin-creatinine ratio (mean difference -69.38, 95% confidence intervals -103.53 to -35.22, P < 0.0001; mean difference -215.74, 95% confidence intervals -409.22 to -22.26, P = 0.03, respectively). A decrease of blood pressure was also found in the co-administration of MRA and ACEI/ARB groups. However, we did not observe any improvement in the glomerular filtration rate. There was a significant increase in the risk of hyperkalemia on the addition of MRA to ACEI/ARB treatment (relative risk 3.74, 95% confidence intervals 2.30-6.09, P < 0.00001). These findings suggest that co-administration of MRA and ACEI/ARB has beneficial effects on renal outcomes with increasing the incidence of hyperkalemia. © 2017 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.
-
Acute bile nephropathy secondary to anabolic steroids.
Alkhunaizi, Ahmed M; ElTigani, Mohamed A; Rabah, Rola S; Nasr, Samih H
2016-02-01
Renal dysfunction in cholestatic liver disease is multifactorial. Acute kidney injury may develop secondary to renal vasoconstriction in the setting of peripheral vasodilation and relative hypovolemia, tubular obstruction by bile casts, and direct tubular toxicity from bile. Anabolic steroids are frequently used by athletes to boost endurance and increase muscle mass. These agents are a recently recognized cause of hepatotoxicity and jaundice and may lead to acute kidney injury. To increase awareness about this growing problem and to characterize the pathology of acute kidney injury in this setting, we report on a young male who developed acute kidney injury in the setting of severe cholestatic jaundice related to ingestion of anabolic steroids used for bodybuilding. Kidney biopsy showed bile casts within distal tubular lumina, filamentous bile inclusions within tubular cells, and signs of acute tubular injury. This report supports the recently re-emerged concept of bile nephropathy cholemic nephrosis.
-
Siddiqui, Shabeena; Ahsan, Haseeb; Khan, Mohammad Rashid; Siddiqui, Waseem A
2013-12-01
Dyslipidemia is common in patients with diabetes mellitus (DM) and is considered a risk factor for the progression of diabetic nephropathy (DN). Hyperlipidemia and hyperglycemia act synergistically to induce renal injury. The present study was designed to investigate the protective effects of tocotrienols as tocotrienol-rich fraction (TRF) extracted from palm (PO) and rice bran oils (RBO) against lipid induced nephropathy in type-2 diabetic rats and its probable molecular mechanism. Male Wistar rats (175-200 g) were divided into four groups. The first group served as diabetic control, while the second and third groups received PO-TRF and RBO-TRF, respectively by gavage over a period of sixteen weeks post-induction of diabetes. The fourth group comprised of age-matched rats that served as normal control. The effects of TRF on serum lipid profile, oxidative stress markers, expression of TGF-β, fibronectin and collagen type IV were analyzed in the kidney of diabetic rats. Treatment with PO-TRF and RBO-TRF significantly improved glycemic status, serum lipid profile and renal function in type-2 diabetic rats. In addition, TRF supplementation down-regulated the expression of TGF-β, fibronectin and collagen type IV in the kidney of diabetic rats. Transforming growth factor-β (TGF-β) plays a critical role in progression of DN, but its modulation by tocotrienols in DN remains unexplored. TRF ameliorated lipid induced nephropathy in type-2 diabetes by its hypoglycemic, hypolipidemic and antioxidant activities as well as by modulation of TGF-β to prevent increased expression of collagen type IV and fibrinogen. We finally propose a mechanism for the expression of molecular markers that are significant in the events leading to diabetic nephropathy and its modulation by tocotrienols/TRF. © 2013.
-
Jatem Escalante, Elías; Segarra Medrano, Alfons; Carnicer Cáceres, Clara; Martín-Gómez, M Adoración; Salcedo Allende, María Teresa; Ostos Roldan, Helena; Agraz Pamplona, Irene
2015-01-01
In membranous nephropathy, the presence of antibodies against M-type phospholipase A2 receptor is considered highly specific for idiopathic forms. However, no specific association to a particular clinical profile has been found for such antibodies. To assess potential differences in initial clinical profile, course and prognosis of idiopathic membranous nephropathy depending on the presence of anti-PLA2R antibodies. Eighty-five patients with idiopathic membranous nephropathy were included (55 anti-PLA2R-positive and 30 anti-PLA2R-negative). Clinical, biochemical and pathological variables were recorded at the time of diagnosis. Frequency of spontaneous remission, incidence of response to first-line therapy, frequency and number of recurrences, survival of renal function free from renal replacement therapy, survival of renal function free from chronic renal insufficiency and frequency of occurrence of malignant, infectious or autoimmune diseases during follow-up were recorded. At the time of diagnosis, anti-PLA2R-negative patients were significantly older and had a higher frequency of spontaneous remission. No differences were noted in the response to first-line treatment, frequency and number of recurrences, survival of renal function free from renal replacement therapy, or survival of renal function free from chronic renal insufficiency. Anti-PLA2R-negative patients with idiopathic membranous nephropathy were older and experienced spontaneous remission more often than anti-PLA2R-positive patients. No differences in terms of treatment response, recurrences, and final prognosis were observed between both groups of patients. Copyright © 2015 The Authors. Published by Elsevier España, S.L.U. All rights reserved.
-
Silveira, Kátia Daniela; Barroso, Lívia Corrêa; Vieira, Angélica Thomáz; Cisalpino, Daniel; Lima, Cristiano Xavier; Bader, Michael; Arantes, Rosa Maria Esteves; dos Santos, Robson Augusto Souza
2013-01-01
Angiotensin-(1–7) [Ang-(1–7)] is a biologically active heptapeptide that may counterbalance the physiological actions of angiotensin II (Ang II) within the renin-angiotensin system (RAS). Here, we evaluated whether activation of the Mas receptor with the oral agonist, AVE 0991, would have renoprotective effects in a model of adriamycin (ADR)-induced nephropathy. We also evaluated whether the Mas receptor contributed for the protective effects of treatment with AT1 receptor blockers. ADR (10 mg/kg) induced significant renal injury and dysfunction that was maximal at day 14 after injection. Treatment with the Mas receptor agonist AVE 0991 improved renal function parameters, reduced urinary protein loss and attenuated histological changes. Renoprotection was associated with reduction in urinary levels of TGF-β. Similar renoprotection was observed after treatment with the AT1 receptor antagonist, Losartan. AT1 and Mas receptor mRNA levels dropped after ADR administration and treatment with losartan reestablished the expression of Mas receptor and increased the expression of ACE2. ADR-induced nephropathy was similar in wild type (Mas+/+) and Mas knockout (Mas −/−) mice, suggesting there was no endogenous role for Mas receptor activation. However, treatment with Losartan was able to reduce renal injury only in Mas+/+, but not in Mas −/− mice. Therefore, these findings suggest that exogenous activation of the Mas receptor protects from ADR-induced nephropathy and contributes to the beneficial effects of AT1 receptor blockade. Medications which target specifically the ACE2/Ang-(1–7)/Mas axis may offer new therapeutic opportunities to treat human nephropathies. PMID:23762470
-
Endemic Scrub Typhus in South America.
Weitzel, Thomas; Dittrich, Sabine; López, Javier; Phuklia, Weerawat; Martinez-Valdebenito, Constanza; Velásquez, Katia; Blacksell, Stuart D; Paris, Daniel H; Abarca, Katia
2016-09-08
Scrub typhus is a life-threatening zoonosis caused by Orientia tsutsugamushi organisms that are transmitted by the larvae of trombiculid mites. Endemic scrub typhus was originally thought to be confined to the so called "tsutsugamushi triangle" within the Asia-Pacific region. In 2006, however, two individual cases were detected in the Middle East and South America, which suggested that the pathogen was present farther afield. Here, we report three autochthonous cases of scrub typhus caused by O. tsutsugamushi acquired on Chiloé Island in southern Chile, which suggests the existence of an endemic focus in South America. (Funded by the Chilean Comisión Nacional de Investigación Científica y Tecnológica and the Wellcome Trust.).
-
ENDEMIC WATERBORNE DISEASE: BENNETT-TYPE
Bennett et al. attempted to estimate national waterborne disease (endemic and epidemic) in 1985 by using both actual data and estimates by CDC experts. These investigators reported that 940,000 cases of waterborne disease and 900 associated deaths could have occurred in the U.S. ...
-
A previously unrecognized role of C3a in proteinuric progressive nephropathy
Morigi, Marina; Locatelli, Monica; Rota, Cinzia; Buelli, Simona; Corna, Daniela; Rizzo, Paola; Abbate, Mauro; Conti, Debora; Perico, Luca; Longaretti, Lorena; Benigni, Ariela; Zoja, Carlamaria; Remuzzi, Giuseppe
2016-01-01
Podocyte loss is the initial event in the development of glomerulosclerosis, the structural hallmark of progressive proteinuric nephropathies. Understanding mechanisms underlying glomerular injury is the key challenge for identifying novel therapeutic targets. In mice with protein-overload induced by bovine serum albumin (BSA), we evaluated whether the alternative pathway (AP) of complement mediated podocyte depletion and podocyte-dependent parietal epithelial cell (PEC) activation causing glomerulosclerosis. Factor H (Cfh−/−) or factor B-deficient mice were studied in comparison with wild-type (WT) littermates. WT+BSA mice showed podocyte depletion accompanied by glomerular complement C3 and C3a deposits, PEC migration to capillary tuft, proliferation, and glomerulosclerosis. These changes were more prominent in Cfh−/− +BSA mice. The pathogenic role of AP was documented by data that factor B deficiency preserved glomerular integrity. In protein-overload mice, PEC dysregulation was associated with upregulation of CXCR4 and GDNF/c-Ret axis. In vitro studies provided additional evidence of a direct action of C3a on proliferation and CXCR4-related migration of PECs. These effects were enhanced by podocyte-derived GDNF. In patients with proteinuric nephropathy, glomerular C3/C3a paralleled PEC activation, CXCR4 and GDNF upregulation. These results indicate that mechanistically uncontrolled AP complement activation is not dispensable for podocyte-dependent PEC activation resulting in glomerulosclerosis. PMID:27345360
-
Renoprotective effect of lansoprazole in streptozotocin-induced diabetic nephropathy in wistar rats.
Kaur, Rupinder; Sodhi, Rupinder Kaur; Aggarwal, Neha; Kaur, Jaspreet; Jain, Upendra K
2016-01-01
Proton pump inhibitors (PPIs) have exhibited glucose lowering action in animal models of diabetes; however, their potential in diabetes-related complications has not yet been evaluated. Hence, the present study has been undertaken to investigate the renoprotective potential of lansoprazole in streptozotocin-induced diabetic nephropathy in wistar rats. Diabetic nephropathy was induced with a single injection of streptozotocin (STZ, 45 mg/kg, i.p.). Lansoprazole (40 mg/kg; 80 mg/kg, p.o.; 4 weeks) was administered to diabetic rats after 4 weeks of STZ treatment. A battery of biochemical tests such as serum glucose, glycated hemoglobin, blood urea nitrogen (BUN), serum creatinine, albumin, and kidney weight/body weight (%) ratio were performed to evaluate the renal functions. Oxidative stress was determined by estimating renal thiobarbituric acid reactive species (TBARS) and reduced glutathione (GSH) levels. Lipid profile was assessed by determining serum cholesterol (TC), triglyceride (TG), and high-density lipoprotein (HDL). The STZ-treated rats demonstrated deleterious alterations in kidney functions, enhanced oxidative stress, and disturbed lipid profile. Administration of lansoprazole to diabetic rats significantly reduced serum glucose, glycated hemoglobin, BUN, creatinine, albumin levels, and oxidative stress. Serum lipids like TC and TG were decreased, and HDL was enhanced in lansoprazole-treated STZ rats. The findings of our study indicate that renoprotective effects of lansoprazole may be attributed to its glucose-lowering, lipid-lowering, and antioxidative potential.
-
Increased Renal Iron Accumulation in Hypertensive Nephropathy of Salt-Loaded Hypertensive Rats
Naito, Yoshiro; Sawada, Hisashi; Oboshi, Makiko; Fujii, Aya; Hirotani, Shinichi; Iwasaku, Toshihiro; Okuhara, Yoshitaka; Eguchi, Akiyo; Morisawa, Daisuke; Ohyanagi, Mitsumasa; Tsujino, Takeshi; Masuyama, Tohru
2013-01-01
Although iron is reported to be associated with the pathogenesis of chronic kidney disease, it is unknown whether iron participates in the pathophysiology of nephrosclerosis. Here, we investigate whether iron is involved in the development of hypertensive nephropathy and the effects of iron restriction on nephrosclerosis in salt- loaded stroke-prone spontaneously hypertensive rats (SHRSP). SHRSP were given either a normal or high-salt diet for 8 weeks. Another subset of SHRSP were fed a high-salt with iron-restricted diet. SHRSP given a high-salt diet developed severe hypertension and nephrosclerosis. As a result, survival rate was decreased after 8 weeks diet. Importantly, massive iron accumulation and increased iron content were observed in the kidneys of salt-loaded SHRSP, along with increased superoxide production, urinary 8-Hydroxy-2′-deoxyguanosine excretion, and urinary iron excretion; however, these changes were markedly attenuated by iron restriction. Of interest, expression of cellular iron transport proteins, transferrin receptor 1 and divalent metal transporter 1, was increased in the tubules of salt-loaded SHRSP. Notably, iron restriction attenuated the development of severe hypertension and nephrosclerosis, thereby improving survival rate in salt-loaded SHRSP. Taken together, these results suggest a novel mechanism by which iron plays a role in the development of hypertensive nephropathy and establish the effects of iron restriction on salt-induced nephrosclerosis. PMID:24116080
-
Role of (Pro)Renin Receptor in Albumin Overload-Induced Nephropathy in Rats.
Fang, Hui; Deng, Mokan; Zhang, Linlin; Lu, Aihua; Su, Jiahui; Xu, Chuanming; Zhou, Li; Wang, Lei; Ou, Jing-Song; Wang, Weidong; Yang, Tianxin
2018-05-30
Proteinuria is not only a common feature of chronic kidney diseases (CKD) but also an independent risk factor promoting CKD progression to end-stage renal failure. However, the underlying molecular mechanisms for protein overload-induced renal injury remain elusive. The present study examined the role of (pro)renin receptor (PRR) in pathogenesis of albumin overload (AO)-induced nephropathy and activation of intrarenal renin-angiotensin system (RAS) in rats. Wistar rats underwent unilateral nephrectomy and were treated for 7 weeks with vehicle, bovine serum albumin (5 g/kg/d via a single i.p. injection) alone or in conjunction with a PRR decoy inhibitor PRO20 (500 μg/kg/d via 3 s.c. injections). The AO rat model exhibited severe proteinuria, tubular necrosis, and interstitial fibrosis, oxidative stress, inflammation, accompanied by elevated urinary N-acetyl-beta-D-glucosaminidase activity and urinary β2-microglobulin secretion, all of which were significantly attenuated by PRO20. Urinary and renal levels of renin, angiotensinogen (AGT), and Ang II were elevated by AO and suppressed by PRO20, contrasting to largely unaltered plasma levels of the RAS parameters. The AO model also showed increased renal expression of full-length PRR and soluble PRR (sPRR) and urinary excretion of sPRR. Taken together, we conclude that PRR antagonism with PRO20 alleviates AO-induced nephropathy via inhibition of intrarenal RAS.
-
Kwakernaak, Arjan J; Krikken, Jan A; Binnenmars, S Heleen; Visser, Folkert W; Hemmelder, Marc H; Woittiez, Arend-Jan; Groen, Henk; Laverman, Gozewijn D; Navis, Gerjan
2014-05-01
Reduction of dietary sodium intake or diuretic treatment increases renin-angiotensin-aldosterone system (RAAS) blockade efficacy in non-diabetic nephropathy. We aimed to investigate the effect of sodium restriction and the diuretic hydrochlorothiazide, separately and in combination, added to RAAS blockade on residual albuminuria in patients with type 2 diabetic nephropathy. In this multicentre, double-blind, placebo-controlled, crossover randomised trial, we included patients with type 2 diabetic nephropathy. Main entry criteria were microalbuminaria or macroalbuminuria, and creatinine clearance of 30 mL/min or higher with less than 6 mL/min decline in the previous year. We tested the separate and combined effects of sodium restriction (dietary counselling in the outpatient setting) and hydrochlorothiazide (50 mg daily), added to standardised maximal angiotensin-converting enzyme (ACE) inhibition (lisinopril 40 mg daily), on albuminuria (primary endpoint). Patients were given hydrochlorothiazide (50 mg per day) or placebo during four treatment periods of 6 weeks. Both treatments were combined with regular sodium diet or sodium restriction (target sodium intake 50 mmol Na(+) per day). The 6-week treatment periods were done consecutively in a random order. Patients were randomised in blocks of two patients. The trial was analysed by intention to treat. The trial is registered with TrialRegister.nl, number 2366. Of 89 eligible patients, 45 were included in the study. Both sodium restriction and hydrochlorothiazide significantly reduced albuminuria, irrespective of treatment sequence. Residual geometric mean albuminuria with baseline treatment was 711 mg per day (95% CI 485-1043); it was significantly reduced by sodium restriction (393 mg per day [258-599], p=0·0002), by hydrochlorothiazide (434 mg per day [306-618], p=0·0003), and to the greatest extent by their combination (306 mg per day [203-461], p<0·0001). Orthostatic complaints were present in two patients (4
-
Spatial distribution of Madeira Island Laurisilva endemic spiders (Arachnida: Araneae)
2014-01-01
Abstract Madeira island presents a unique spider diversity with a high number of endemic species, many of which are still poorly known. A recent biodiversity survey on the terrestrial arthropods of the native forest, Laurisilva, provided a large set of standardized samples from various patches throughout the island. Out of the fifty two species recorded, approximately 33.3% are Madeiran endemics, many of which had not been collected since their original description. Two new species to science are reported – Ceratinopsis n. sp. and Theridion n. sp. – and the first records of Poeciloneta variegata (Blackwall, 1841) and Tetragnatha intermedia Kulczynski, 1891 are reported for the first time for Madeira island. Considerations on species richness and abundance from different Laurisilva locations are presented, together with distribution maps for endemic species. These results contribute to a better understanding of spider diversity patterns and endemic species distribution in the native forest of Madeira island. PMID:24855443
-
Veloso, Mariana P; Neves, Precil D M M; Jorge, Lectícia B; Dias, Cristiane B; Yu, Luis; Pinheiro, Rafaela B B; Testagrossa, Leonardo A; Malheiros, Denise M; Balbo, Bruno E P; Lerário, Antônio M; Onuchic, Luiz F; Woronik, Viktoria
2017-01-01
Alport syndrome (AS) is a disorder of collagen IV, a component of glomerular basement membrane (GBM). The association of AS and immunocomplex nephropathies is uncommon. This is a case of a 37-year-old woman with family history of X-linked AS, including 4 affected sons. This patient developed full-blown nephrotic syndrome along a 3-month period, a presentation not consistent with AS progression. This scenario suggested an alternative diagnosis. A kidney biopsy was therefore performed, showing membranous nephropathy (MN) in addition to GBM structural alterations compatible with AS. Whole exome sequencing also confirmed the diagnosis of X-linked AS, revealing a heterozygous pathogenic mutation in COL4A5. While a negative serum anti-phospholipase A2 receptor did not rule out a primary form of MN, it was also uncertain whether positive serologic tests for syphilis could represent a secondary factor. It is currently unknown whether this unusual association represents AS susceptibility to immunocomplex-mediated diseases or simply an association of 2 disorders. © 2017 S. Karger AG, Basel.
-
Toyoda, Kaoru; Suzuki, Yusuke; Muta, Kyotaka; Masuyama, Taku; Kakimoto, Kochi; Kobayashi, Akio; Shoda, Toshiyuki; Sugai, Shoichiro
2018-01-01
Diabetic nephropathy (DN) is one of the complications of diabetes and is now the most common cause of end-stage renal disease. Fructose is a simple carbohydrate that is present in fruits and honey and is used as a sweetener because of its sweet taste. Fructose has been reported to have the potential to progress diabetes and DN in humans even though fructose itself does not increase postprandial plasma glucose levels. In this study, we investigated the effects of high fructose intake on the kidney of the Spontaneously Diabetic Torii (SDT) rats which have renal lesions similar to those in DN patients and compared these with the effects in normal SD rats. This study revealed that a 4-week feeding of the high fructose diet increased urinary excretion of kidney injury makers for tubular injury and accelerated mainly renal tubular and interstitial lesions in the SDT rats but not in normal rats. The progression of the nephropathy in the SDT rats was considered to be related to increased internal uric acid and blood glucose levels due to the high fructose intake. In conclusion, high fructose intake exaggerated the renal lesions in the SDT rats probably due to effects on the tubules and interstitium through metabolic implications for uric acid and glucose.
-
Herrera, Guillermo A; Ojemakinde, Kunle O; Turbat-Herrera, Elba A; Gu, Xin; Zeng, Xu; Iskandar, Samy S
2015-01-01
Immunotactoid glomerulopathy is a rare disorder that has been characterized at the ultrastructural level. Due to its rarity, there are few comprehensive studies relating to this disorder. Electron microscopy essentially characterizes this disease. The glomerular electron dense deposits which are typical of this condition consist of aggregates of highly organized microtubular structures of various diameters, but generally measuring 30-50 nm in width with a propensity to dispose themselves in parallel bundles intersecting in different planes. This study compares a large series of patients with cryoglobulinemic nephropathy with a series of patients with immunotactoid glomerulopathy to address whether there may be similarities that warrant considering these two entities part of a spectrum. This study reviews the clinicopathologic features of both entities and emphasizes ultrastructural findings that characterize them. Significant immunomorphologic overlap was found when these two disorders were compared in this study. There were also striking similarities in clinical presentation/behavior, laboratory findings and prognosis. Proteomic analysis has also demonstrated similar spectra for both entities. We postulate that immunotactoid glomerulopathy and cryoglobulinemic nephropathy are part of the spectrum of renal manifestations in patients with circulating cryoglobulins and renal disease.
-
Bakris, George; Burgess, Ellen; Weir, Matthew; Davidai, Giora; Koval, Stephen
2008-08-01
In patients with diabetic nephropathy, lowering blood pressure and reducing proteinuria by over 30% correlates with a slower progression to kidney failure. We compared two different angiotensin receptor-blockers in a double blind, prospective trial of 860 patients with type 2 diabetes whose blood pressure levels was over 130/80 mmHg or who were receiving antihypertensive medication(s) and who had a morning spot urinary protein to creatinine ratio of 700 or more. Patients were randomized to telmisartan (a highly lipophilic agent with a long half-life) or losartan (with low lipophilicity and short half-life). The primary endpoint was the difference in the urinary albumin to creatinine ratio between the groups at 52 weeks. The geometric coefficient of variation and the mean of the urinary albumin to creatinine ratio fell in both groups at 52 weeks but both were significantly greater for the telmisartan compared to the losartan cohort. Mean systolic blood pressure reductions were not significantly different between groups at trial end. We conclude that telmisartan is superior to losartan in reducing proteinuria in hypertensive patients with diabetic nephropathy, despite a similar reduction in blood pressure.
-
Sai Varsha, M K N; Raman, Thiagarajan; Manikandan, R; Dhanasekaran, G
2015-10-01
Vitamin K is a potent regulator of vascular dynamics and prevents vascular calcification. Vitamin K is increasingly being recognized for its antioxidant and antiinflammatory properties. Recently we demonstrated that vitamin K1 (5 mg/kg) protects against streptozotocin-induced type 1 diabetes and diabetic cataract. The aim of this study was to determine whether the hypoglycemic action of vitamin K1 could inhibit early-onset diabetic nephropathy in a streptozotocin-induced rat kidney. Male Wistar rats were administered with 35 mg/kg STZ and after 3 days were treated with vitamin K1 (5 mg/kg, twice a week) for 3 months. Blood glucose was monitored once a month. At the end of the study, animals were sacrificed and kidney was dissected out and analysed for free radicals, antioxidants, aldose reductase, membrane ATPases, histopathology evaluation and expression of pro- and anti-inflammatory cytokines. Urea, uric acid, creatinine, albumin and insulin levels were also estimated. Treatment of diabetic rats with vitamin K1 resulted in a decrease in blood glucose and prevented microalbuminuria. Vitamin K1 also reduced oxidative stress and protected renal physiology by modulating Ca(2+) and Na(+)/K(+)-ATPases. Vitamin K1 inhibited renal inflammation by reducing nuclear factor-κB and inducible nitric oxide synthase. Interleukin-10 levels were increased in renal tissues, suggesting the ability of vitamin K1 to trigger antiinflammatory state. The hypoglycemic action of vitamin K1 could have an indirect effect by inhibiting early-onset diabetic nephropathy triggered by high blood glucose. Vitamin K1 could be an important nutrient based interventional strategy for early onset diabetic nephropathy. Copyright © 2015 Elsevier Inc. All rights reserved.
-
Endemicity and epidemicity of cholera
Kamal, A. M.
1963-01-01
In this review of the factors governing the endemicity and epidemicity of cholera, special attention is paid to attempts to demarcate endemic areas by statistical methods, in particular by the use of Swaroop's “index of endemicity”. Once such areas are delineated, it is possible to assess the characteristic features—such as the presence of numerous water tanks, the heavy pollution of water in the dry season, and socio-cultural factors—which help to maintain continuity of infection. While some of the causes underlying epidemic outbreaks of cholera are still obscure, it is clear that these outbreaks derive in large part from the introduction of infection into communities whose members have no immunity (or have lost their immunity) to cholera, and that a very important role is played here by movements of groups of the population—particularly, in India, the movement of pilgrims and others to and from fairs and festivals. PMID:14030417
-
Endemic Sardinian plants: the case of Genista cadasonensis Valsecchi.
Serrilli, Anna Maria; Graziosi, Valentina; Ballero, Mauro; Foddis, Caterina; Serafini, Mauro; Poli, Ferruccio; Scartezzini, Paolo; Bianco, Armandodoriano
2010-06-01
The flavonoid fraction of the aerial parts of Genista cadasonensis Valsecchi (Leguminosae), an endemic plant from Sardinia, was examined and compared with the flavonoid pattern already known in the Genista genus. This comparison evidenced the endemic nature of this species, showing the presence of a rare flavonoid, the 6-hydroxy-genistein. The antioxidant activity of dichloromethanic, ethanolic and acetonic total extracts of aerial parts was evaluated.
-
Evolution of endemism on a young tropical mountain.
Merckx, Vincent S F T; Hendriks, Kasper P; Beentjes, Kevin K; Mennes, Constantijn B; Becking, Leontine E; Peijnenburg, Katja T C A; Afendy, Aqilah; Arumugam, Nivaarani; de Boer, Hugo; Biun, Alim; Buang, Matsain M; Chen, Ping-Ping; Chung, Arthur Y C; Dow, Rory; Feijen, Frida A A; Feijen, Hans; Feijen-van Soest, Cobi; Geml, József; Geurts, René; Gravendeel, Barbara; Hovenkamp, Peter; Imbun, Paul; Ipor, Isa; Janssens, Steven B; Jocqué, Merlijn; Kappes, Heike; Khoo, Eyen; Koomen, Peter; Lens, Frederic; Majapun, Richard J; Morgado, Luis N; Neupane, Suman; Nieser, Nico; Pereira, Joan T; Rahman, Homathevi; Sabran, Suzana; Sawang, Anati; Schwallier, Rachel M; Shim, Phyau-Soon; Smit, Harry; Sol, Nicolien; Spait, Maipul; Stech, Michael; Stokvis, Frank; Sugau, John B; Suleiman, Monica; Sumail, Sukaibin; Thomas, Daniel C; van Tol, Jan; Tuh, Fred Y Y; Yahya, Bakhtiar E; Nais, Jamili; Repin, Rimi; Lakim, Maklarin; Schilthuizen, Menno
2015-08-20
Tropical mountains are hot spots of biodiversity and endemism, but the evolutionary origins of their unique biotas are poorly understood. In varying degrees, local and regional extinction, long-distance colonization, and local recruitment may all contribute to the exceptional character of these communities. Also, it is debated whether mountain endemics mostly originate from local lowland taxa, or from lineages that reach the mountain by long-range dispersal from cool localities elsewhere. Here we investigate the evolutionary routes to endemism by sampling an entire tropical mountain biota on the 4,095-metre-high Mount Kinabalu in Sabah, East Malaysia. We discover that most of its unique biodiversity is younger than the mountain itself (6 million years), and comprises a mix of immigrant pre-adapted lineages and descendants from local lowland ancestors, although substantial shifts from lower to higher vegetation zones in this latter group were rare. These insights could improve forecasts of the likelihood of extinction and 'evolutionary rescue' in montane biodiversity hot spots under climate change scenarios.
-
Enhancing Surveillance and Diagnostics in Anthrax-Endemic Countries
Salzer, Johanna S.; Traxler, Rita M.; Hendricks, Katherine A.; Kadzik, Melissa E.; Marston, Chung K.; Kolton, Cari B.; Stoddard, Robyn A.; Hoffmaster, Alex R.; Bower, William A.; Walke, Henry T.
2017-01-01
Naturally occurring anthrax disproportionately affects the health and economic welfare of poor, rural communities in anthrax-endemic countries. However, many of these countries have limited anthrax prevention and control programs. Effective prevention of anthrax outbreaks among humans is accomplished through routine livestock vaccination programs and prompt response to animal outbreaks. The Centers for Disease Control and Prevention uses a 2-phase framework when providing technical assistance to partners in anthrax-endemic countries. The first phase assesses and identifies areas for improvement in existing human and animal surveillance, laboratory diagnostics, and outbreak response. The second phase provides steps to implement improvements to these areas. We describe examples of implementing this framework in anthrax-endemic countries. These activities are at varying stages of completion; however, the public health impact of these initiatives has been encouraging. The anthrax framework can be extended to other zoonotic diseases to build on these efforts, improve human and animal health, and enhance global health security. PMID:29155651
-
Sharma, Ashish Kumar; Kanawat, Devendra Singh; Mishra, Akanksha; Dhakad, Prashant Kumar; Sharma, Prashant; Srivastava, Varnika; Joshi, Sneha; Joshi, Megha; Raikwar, Sachin Kumar; Kurmi, Muneem Kumar; Srinivasan, Bharthu Parthsarthi
2014-12-01
The objective of this article is to investigate the combination of telmisartan with vildagliptin therapy versus monotherapy of vildagliptin and telmisartan on diabetic nephropathy in type 2 diabetes mellitus rats. In adult rats streptozotocin (65 mg/kg) and nicotinamide (110 mg/kg) were injected intraperitoneally to produce diabetic nephropathy. Rats of either sex allotted to the following groups: (i) triple therapy: metformin (120 mg/kg, o.d.) + pioglitazone (1.25 mg/kg, o.d.) + glimepiride (0.7 mg/kg, o.d.); (ii) dual therapy: vildagliptin (8.76 mg/kg, o.d.) + telmisartan (6.48 mg/kg, o.d.); (iii) vildagliptin (8.76 mg/kg, o.d.); and (iv) telmisartan (6.48 mg/kg, o.d.); therapy was carried out for 35 days orally. Weekly at days 7, 14, 21, 28 and 35, blood pressure, blood glucose level, body weight, blood serum creatinine level, protein albumin level in urine, and blood urea nitrogen (BUN) were estimated. Renal structural changes were observed. Blood pressure, blood glucose level, blood serum creatinine level, protein albumin level in urine, BUN and renal deterioration increased significantly in diabetic rats compared with normal control rats. The vildagliptin + telmisartan treatment group showed no weight gain and controlled blood pressure, renovascular structural and biochemical parameters in diabetic neuropathy rats. The addition of telmisartan to vildagliptin demonstrated the best control over blood pressure, glycemia and diabetic nephropathy markers, renal structural changes and improvement of renal function as opposed to monotherapy with either drug, possibly because of the dual inhibitory effect on the renin-angiotensin system. © The Author(s) 2013.
-
The mammalian faunas endemic to the Cerrado and the Caatinga.
Gutiérrez, Eliécer E; Marinho-Filho, Jader
2017-01-01
We undertook a comprehensive, critical review of literature concerning the distribution, conservation status, and taxonomy of species of mammals endemic to the Cerrado and the Caatinga, the two largest biomes of the South American Dry-Diagonal. We present species accounts and lists of species, which we built with criteria that, in our opinion, yielded results with increased scientific rigor relative to previously published lists - e.g., excluding nominal taxa whose statuses as species have been claimed only on the basis of unpublished data, incomplete taxonomic work, or weak evidence. For various taxa, we provided arguments regarding species distributions, conservation and taxonomic statuses previously lacking in the literature. Two major findings are worth highlighting. First, we unveil the existence of a group of species endemic to both the Cerrado and the Caatinga (i.e., present in both biomes and absent in all other biomes). From the biogeographic point of view, this group, herein referred to as Caatinga-Cerrado endemics, deserves attention as a unit - just as in case of the Caatinga-only and the Cerrado-only endemics. We present preliminary hypotheses on the origin of these three endemic faunas (Cerrado-only, Caatinga-only, and Caatinga-Cerrado endemics). Secondly, we discovered that a substantial portion of the endemic mammalian faunas of the Caatinga and the Cerrado faces risks of extinction that are unrecognized in the highly influential Red List of Threatened Species published by the International Union for Conservation of Nature (IUCN). "Data deficient" is a category that misrepresents the real risks of extinction of these species considering that (a) some of these species are known only from a handful of specimens collected in a single or a few localities long ago; (b) the Cerrado and the Caatinga have been sufficiently sampled to guarantee collection of additional specimens of these species if they were abundant; (c) natural habitats of the Cerrado and
-
The mammalian faunas endemic to the Cerrado and the Caatinga
Gutiérrez, Eliécer E.; Marinho-Filho, Jader
2017-01-01
Abstract We undertook a comprehensive, critical review of literature concerning the distribution, conservation status, and taxonomy of species of mammals endemic to the Cerrado and the Caatinga, the two largest biomes of the South American Dry-Diagonal. We present species accounts and lists of species, which we built with criteria that, in our opinion, yielded results with increased scientific rigor relative to previously published lists – e.g., excluding nominal taxa whose statuses as species have been claimed only on the basis of unpublished data, incomplete taxonomic work, or weak evidence. For various taxa, we provided arguments regarding species distributions, conservation and taxonomic statuses previously lacking in the literature. Two major findings are worth highlighting. First, we unveil the existence of a group of species endemic to both the Cerrado and the Caatinga (i.e., present in both biomes and absent in all other biomes). From the biogeographic point of view, this group, herein referred to as Caatinga-Cerrado endemics, deserves attention as a unit – just as in case of the Caatinga-only and the Cerrado-only endemics. We present preliminary hypotheses on the origin of these three endemic faunas (Cerrado-only, Caatinga-only, and Caatinga-Cerrado endemics). Secondly, we discovered that a substantial portion of the endemic mammalian faunas of the Caatinga and the Cerrado faces risks of extinction that are unrecognized in the highly influential Red List of Threatened Species published by the International Union for Conservation of Nature (IUCN). “Data deficient” is a category that misrepresents the real risks of extinction of these species considering that (a) some of these species are known only from a handful of specimens collected in a single or a few localities long ago; (b) the Cerrado and the Caatinga have been sufficiently sampled to guarantee collection of additional specimens of these species if they were abundant; (c) natural habitats of
-
Acute oxalate nephropathy due to 'Averrhoa bilimbi' fruit juice ingestion.
Bakul, G; Unni, V N; Seethaleksmy, N V; Mathew, A; Rajesh, R; Kurien, G; Rajesh, J; Jayaraj, P M; Kishore, D S; Jose, P P
2013-07-01
Irumban puli (Averrhoa bilimbi) is commonly used as a traditional remedy in the state of Kerala. Freshly made concentrated juice has a very high oxalic acid content and consumption carries a high risk of developing acute renal failure (ARF) by deposition of calcium oxalate crystals in renal tubules. Acute oxalate nephropathy (AON) due to secondary oxalosis after consumption of Irumban puli juice is uncommon. AON due to A. bilimbi has not been reported before. We present a series of ten patients from five hospitals in the State of Kerala who developed ARF after intake of I. puli fruit juice. Seven patients needed hemodialysis whereas the other three improved with conservative management.
-
Schalkwijk, C G; Chaturvedi, N; Twaafhoven, H; van Hinsbergh, V W M; Stehouwer, C D A
2002-07-01
Amadori-albumin, a major glycated protein, is involved in experimental hyperglycaemia-induced microvascular complications, and is associated with advanced nephropathy in Type I diabetic patients in humans. Our aim was to assess the association of Amadori-albumin with early nephropathy and with retinopathy in Type I diabetic patients and the involvement of chronic low-degree inflammation therein. Amadori-albumin, the Amadori product of haemoglobin (HbA1c), C-reactive protein, and fibrinogen levels were measured in the EUCLID study, a 2-year randomised, double-blind, placebo-controlled trial of lisinopril in 447 Type I diabetic patients. Retinal photographs were taken in 341 patients at baseline and 294 at follow up. Amadori-albumin was positively associated with albumin the excretion rate and retinopathy status (P = 0.0001 and P = 0.02 for trend, respectively) and with the progression from normoalbuminuria to (micro)albuminuria (38.6 U mL(-1) in nonprogressors, 44.3 U mL-1 in progressors; P = 0.02), but not with the development or progression of retinopathy during a 2-year follow up. Amadori-albumin levels at baseline were associated with C-reactive protein and fibrinogen (P = 0.0007 and P = 0.0001, respectively). C-reactive protein and fibrinogen were also associated with albumin excretion rates (P = 0.03 and P = 0.01, respectively) and retinopathy status (P = 0.02 and P = 0.0006, respectively). Adjustment for these inflammatory markers did not markedly attenuate the association between Amadori-albumin and the albumin excretion rate, while adjustment for fibrinogen, but not C-reactive protein, abolished the association between Amadori-albumin and retinopathy. Lisinopril had no impact on the association between the levels of Amadori-albumin and albumin excretion rates or retinopathy. Amadori-albumin was associated with early nephropathy and with retinopathy in Type I diabetic patients and preceded an increase in albumin excretion rate, but not retinopathy. A chronic
-
Tabatabaei-Malazy, Ozra; Atlasi, Rasha; Larijani, Bagher; Abdollahi, Mohammad
2015-01-01
Recently, popularity and use of herbal medicine in treatment of diabetes have been increased. Since, oxidative stress is known as the main underlying pathophysiology of diabetes and its complications, the purpose of this bibliometric study is to assess the global scientific production analysis and developing its trend in field of antioxidative hypoglycemic herbal medicines and diabetic nephropathy focusing on the scientific publication numbers, citations, geographical distribution in the world and determining the main journal (source) in the field. Our search terms were "diabetes", "renal", "nephropathy", "herb", "Chinese medicine", "traditional medicine", and "antioxidant" from Scopus database until January 2015 and analysis of the distribution of words in the publication year, main journal (source) in the field, geographical distribution, documents' type and language, subject area, and h-index of citations were crried out. The Scopus analysis tools and VOSviewer software version 1.6.3 have been used for analysis. Within 1166 papers were published until year 2015, 78 studies were related to this topic in human. Increasing trend in number of related researches was shown. Fifty eight percent of the published papers were original articles, and the highest number was produced in 2013 with 21 documents. Top subject areas were medicine with global publication share of 71.8 %, and pharmacology was ranked the second (39.7 %). Iran was the first country with global publication. The total citation of the documents were 2518 times and h-index was 24. The highest cited paper was a review article with 336 citation number, and top source was "Journal of Medicinal Plants". Both of top authors and affiliation were from Iran; "Tehran University of Medical Sciences". Also, top author in the co-authorship mapping and clustering assessment was from Iran. Although, we found an ascending trend of scientific publications in field of antioxidative herbal medicine and diabetic
-
[Clinical and histological findings in Fabry nephropathy].
Pieruzzi, Federico; Salerno, Fabio; Di Giacomo, Antonella; Torti, Giacomo; Ferrario, Franco; Pagni, Fabio; Stella, Andrea
2013-01-01
Fabry disease is a complex pathology, requiring a multidisciplinar approach both in the diagnostic workout and in the management of therapy. Clinical criteria able to predict its morbidity have not yet been found. The wide variability of clinical signs and symptoms requires an individual approach based on the single patient, in order to achieve an optimal management. Enzyme replacement therapy (ERT) has been introduced in the clinical setting for over ten years, but its ability to change the course of the disease has not yet been clearly proved. Recently the hypothesis that ERT may be ineffective in patients with severe organ involvement has emerged. The clinical course of Fabry disease is usually slower in eterozygous women than emizygous men, but can be frequently associated to severe organ failure and premature death in both cases. In this review we discuss the histological aspects of Fabry nephropathy in relation to diagnosis, prognosis, therapy and its effectiveness.
-
Lazarevik, Vladimir; Kasapinov, Blasko
2015-02-01
Patients' satisfaction with provided healthcare services is one of the factors to measure the overall quality of the delivered health care. Main objective of our study was to determine the common predictors associated with patients 'satisfaction in three Balkan countries. We conducted web based survey among population in Macedonia, Serbia and Bulgaria using paid campaign over the social network Facebook. A questionnaire consisted of 31 questions was developed following studies on patients' satisfaction conducted elsewhere. Descriptive analysis was performed to assess the predictors associated with patients' satisfaction. In addition we performed content analysis to all open-ended responses. In total 4118 respondents participated in the survey. Main predictors associated with low users satisfaction with the health care services in three surveyed countries are waiting time to appointments, huge administrative procedures, and attitudes of the medical personnel towards the patients. The analysis showed that there are many similarities in user experiences in three countries, but also there are some differences. The health care systems in these three counties are organized around centralized and monopolistic position of one health insurance fund that serves as main purchaser of health care services. Top three indicators of patients' satisfaction across three countries are trust and overall satisfaction with the attention of the doctors, as well as satisfaction with the outcome of the treatment. Long waiting time and huge administrative procedures are determined as common predictor for lower patients' satisfaction across these Balkan countries. Patients' privacy protection is issue for concern in all three countries.
-
Erratum to: When violence becomes endemic.
Roberts, Leslie F
2018-05-01
The article "When violence becomes endemic", written by Leslie F. Roberts, was originally published electronically on the publisher's internet portal (currently SpringerLink) on 03 August 2017 without open access. The original article was corrected.
-
Pal, Pabitra Bikash; Sinha, Krishnendu; Sil, Parames C.
2014-01-01
Oxidative stress plays a crucial role in the progression of diabetic nephropathy in hyperglycemic conditions. It has already been reported that mangiferin, a natural C-glucosyl xanthone and polyhydroxy polyphenol compound protects kidneys from diabetic nephropathy. However, little is known about the mechanism of its beneficial action in this pathophysiology. The present study, therefore, examines the detailed mechanism of the beneficial action of mangiferin on STZ-induced diabetic nephropathy in Wister rats as the working model. A significant increase in plasma glucose level, kidney to body weight ratio, glomerular hypertrophy and hydropic changes as well as enhanced nephrotoxicity related markers (BUN, plasma creatinine, uric acid and urinary albumin) were observed in the experimental animals. Furthermore, increased oxidative stress related parameters, increased ROS production and decreased the intracellular antioxidant defenses were detected in the kidney. Studies on the oxidative stress mediated signaling cascades in diabetic nephropathy demonstrated that PKC isoforms (PKCα, PKCβ and PKCε), MAPKs (p38, JNK and ERK1/2), transcription factor (NF-κB) and TGF-β1 pathways were involved in this pathophysiology. Besides, TNFα was released in this hyperglycemic condition, which in turn activated caspase 8, cleaved Bid to tBid and finally the mitochorndia-dependent apoptotic pathway. In addition, oxidative stress also disturbed the proapoptotic-antiapoptotic (Bax and Bcl-2) balance and activated mitochorndia-dependent apoptosis via caspase 9, caspase 3 and PARP cleavage. Mangiferin treatment, post to hyperglycemia, successfully inhibited all of these changes and protected the cells from apoptotic death. PMID:25233093
-
Veličković, Vladica; Jović, Marko; Nalić, Ena; Višnjić, Aleksandar; Radulović, Olivera; Šagrić, Čedomir; Ćirić, Milan
2016-01-01
There are still no data on the attitudes and acceptance of genetic modification (GM) food in European developing countries, such as the Western Balkan countries. The aim of the study was to assess the knowledge, attitudes, and acceptance of GM but also to shed light on the multifactorial process leading to acceptance of genetic modifications among Western Balkan students of life sciences. In this cross-sectional study, the final study population sample was composed of 1251 university students. The instrument for data collection was a questionnaire consisting of 49 items composed of 5 sections taken from the literature. Attitudes toward GM were analyzed by using Q-mode factor analysis and principal component analysis was run for the assessment of perception of personal health risks. The acceptability of GM was analyzed in binary probit models assessing the acceptability of GM products in different areas of application with Q models, sociodemographic variables, perception of personal health risks factors, respondents' knowledge about biotechnology, gender, and age as explanatory variables. This study demonstrated that students of life sciences supported the implementation of GM in industry and medicine production but not in food production. Their acceptance was most influenced by 3 out of 5 attitude models that were identified (p < 0.0001). Regarding the perception of personal health risks, the factor "credence risks" was seen as a negative predictor of acceptance of GM in industry and food production (p < 0.05). The main knowledge predictor of rejecting GM was misconception, whereas real knowledge had no impact (p < 0.0001). The AGREE study provided the first rough picture of the knowledge, attitudes, and acceptance of GM in this area. Given the target population, it could be expected that the general population's acceptance of all observed elements, especially knowledge, would be lower.
-
Mapping Soil Erosion Factors and Potential Erosion Risk for the National Park "Central Balkan"
NASA Astrophysics Data System (ADS)
Ilieva, Diliana; Malinov, Ilia
2014-05-01
Soil erosion is widely recognised environmental problem. The report aims at presenting the main results from assessment and mapping of the factors of sheet water erosion and the potential erosion risk on the territory of National Park "Central Balkan". For this purpose, the Universal Soil Loss Equation (USLE) was used for predicting soil loss from erosion. The influence of topography (LS-factor) and soil erodibility (K-factor) was assessed using small-scale topographic and soil maps. Rainfall erosivity (R-factor) was calculated from data of rainfalls with amounts exceeding 9.5 mm from 14 hydro-meteorological stations. The values of the erosion factors (R, K and LS) were presented for the areas of forest, sub-alpine and alpine zones. Using the methods of GIS, maps were plotted presenting the area distribution among the classes of the soil erosion factors and the potential risk in the respective zones. The results can be used for making accurate decisions for soil conservation and sustainable land management in the park.
-
NASA Astrophysics Data System (ADS)
van der Meer, M. H.; Berumen, M. L.; Hobbs, J.-P. A.; van Herwerden, L.
2015-06-01
Marine protected areas (MPAs) aim to mitigate anthropogenic impacts by conserving biodiversity and preventing overfishing. The effectiveness of MPAs depends on population connectivity patterns between protected and non-protected areas. Remote islands are endemism hotspots for coral reef fishes and provide rare examples of coral reefs with limited fishing pressure. This study explored population genetic connectivity across a network of protected and non-protected areas for the endemic wrasse, Coris bulbifrons, which is listed as "vulnerable" by the IUCN due to its small, decreasing geographic range and declining abundance. Mitochondrial DNA (mtDNA) and microsatellite DNA (msatDNA) markers were used to estimate historic and contemporary gene flow to determine the level of population self-replenishment and to measure genetic and genotypic diversity among all four locations in the species range (south-west Pacific Ocean)—Middleton Reef (MR), Elizabeth Reef (ER), Lord Howe Island (LHI) and Norfolk Island (NI). MPAs exist at MR and LHI and are limited or non-existent at ER and NI, respectively. There was no obvious differentiation in mtDNA among locations, however, msatDNA revealed differentiation between the most peripheral (NI) and all remaining locations (MR, ER and LHI). Despite high mtDNA connectivity ( M = 259-1,144), msatDNA connectivity was limited ( M = 3-9) with high self-replenishment (68-93 %) at all locations. NI is the least connected and heavily reliant on self-replenishment, and the absence of MPAs at NI needs to be rectified to ensure the persistence of endemic species at this location. Other endemic fishes exhibit similar patterns of high self-replenishment across the four locations, indicating that a single spatial management approach consisting of a MPA network protecting part of each location could provide reasonable protection for these species. Thus, the existing network of MPAs at this endemic hotspot appears adequate at some locations, but not
-
Heerspink, Hiddo J. L.; Andress, Dennis L.; Bakris, George; Brennan, John J.; Correa‐Rotter, Ricardo; Dey, Jyotirmoy; Hou, Fan Fan; Kitzman, Dalane W.; Kohan, Donald; Makino, Hirofumi; McMurray, John; Perkovic, Vlado; Tobe, Sheldon; Wigderson, Melissa; Parving, Hans‐Henrik
2018-01-01
Aims Individuals with diabetes and chronic kidney disease (CKD) are at high risk for renal events. Recent trials of novel treatments have been negative, possibly because of variability in response to treatment of the target risk factor. Atrasentan is a selective endothelin A receptor antagonist that reduces urinary albumin‐to‐creatinine ratio (UACR), with a large variability between patients. We are assessing its effect on renal outcomes in the Study Of diabetic Nephropathy with AtRasentan (SONAR; NCT01858532) with an enrichment design (>30% lowering of albuminuria) to select patients most likely to benefit. Materials and Methods SONAR is a randomized, double‐blind, placebo‐controlled trial with approximately 3500 participants who have stage 2–4 CKD and macroalbuminuria and are receiving a maximum tolerated dose of a renin‐angiotensin system inhibitor. Results After 6 weeks of exposure to atrasentan 0.75 mg once daily (enrichment period), participants with ≥30% UACR decrease and no tolerability issues (responders) were randomly assigned to placebo or atrasentan 0.75 mg/day. The responder group will be used for primary efficacy and safety analyses. Approximately 1000 participants with <30% UACR reduction (non‐responders) were also randomized to placebo or atrasentan. The primary endpoint is a composite of a sustained doubling of serum creatinine or end‐stage renal disease. The original power calculation indicated that a total of 425 primary renal events in the responder group provides 90% power to detect a 27% reduction in relative risk (alpha level of .05). Conclusion SONAR aims to determine whether atrasentan added to guideline‐recommended therapies safely reduces the risk of CKD progression and delays the onset of end‐stage renal disease in patients with type 2 diabetes and nephropathy. SONAR also aims to establish whether the enrichment of patients based on their initial “surrogate” response to atrasentan will deliver a trial
-
Heerspink, Hiddo J L; Andress, Dennis L; Bakris, George; Brennan, John J; Correa-Rotter, Ricardo; Dey, Jyotirmoy; Hou, Fan Fan; Kitzman, Dalane W; Kohan, Donald; Makino, Hirofumi; McMurray, John; Perkovic, Vlado; Tobe, Sheldon; Wigderson, Melissa; Parving, Hans-Henrik; de Zeeuw, Dick
2018-06-01
Individuals with diabetes and chronic kidney disease (CKD) are at high risk for renal events. Recent trials of novel treatments have been negative, possibly because of variability in response to treatment of the target risk factor. Atrasentan is a selective endothelin A receptor antagonist that reduces urinary albumin-to-creatinine ratio (UACR), with a large variability between patients. We are assessing its effect on renal outcomes in the Study Of diabetic Nephropathy with AtRasentan (SONAR; NCT01858532) with an enrichment design (>30% lowering of albuminuria) to select patients most likely to benefit. SONAR is a randomized, double-blind, placebo-controlled trial with approximately 3500 participants who have stage 2-4 CKD and macroalbuminuria and are receiving a maximum tolerated dose of a renin-angiotensin system inhibitor. After 6 weeks of exposure to atrasentan 0.75 mg once daily (enrichment period), participants with ≥30% UACR decrease and no tolerability issues (responders) were randomly assigned to placebo or atrasentan 0.75 mg/day. The responder group will be used for primary efficacy and safety analyses. Approximately 1000 participants with <30% UACR reduction (non-responders) were also randomized to placebo or atrasentan. The primary endpoint is a composite of a sustained doubling of serum creatinine or end-stage renal disease. The original power calculation indicated that a total of 425 primary renal events in the responder group provides 90% power to detect a 27% reduction in relative risk (alpha level of .05). SONAR aims to determine whether atrasentan added to guideline-recommended therapies safely reduces the risk of CKD progression and delays the onset of end-stage renal disease in patients with type 2 diabetes and nephropathy. SONAR also aims to establish whether the enrichment of patients based on their initial "surrogate" response to atrasentan will deliver a trial design in accord with personalized treatment of diabetic kidney disease.
-
Endemic Mimosa species from Mexico prefer alphaproteobacterial rhizobial symbionts.
Bontemps, Cyril; Rogel, Marco Antonio; Wiechmann, Anja; Mussabekova, Assel; Moody, Sarah; Simon, Marcelo F; Moulin, Lionel; Elliott, Geoffrey N; Lacercat-Didier, Laurence; Dasilva, Cindy; Grether, Rosaura; Camargo-Ricalde, Sara L; Chen, Weimin; Sprent, Janet I; Martínez-Romero, Esperanza; Young, J Peter W; James, Euan K
2016-01-01
The legume genus Mimosa has > 500 species, with two major centres of diversity, Brazil (c. 350 spp.) and Mexico (c. 100 spp.). In Brazil most species are nodulated by Burkholderia. Here we asked whether this is also true of native and endemic Mexican species. We have tested this apparent affinity for betaproteobacteria by examining the symbionts of native and endemic species of Mimosa in Mexico, especially from the central highlands where Mimosa spp. have diversified. Nodules were tested for betaproteobacteria using in situ immunolocalization. Rhizobia isolated from the nodules were genetically characterized and tested for their ability to nodulate Mimosa spp. Immunological analysis of 25 host taxa suggested that most (including all the highland endemics) were not nodulated by betaproteobacteria. Phylogenetic analyses of 16S rRNA, recA, nodA, nodC and nifH genes from 87 strains isolated from 20 taxa confirmed that the endemic Mexican Mimosa species favoured alphaproteobacteria in the genera Rhizobium and Ensifer: this was confirmed by nodulation tests. Host phylogeny, geographic isolation and coevolution with symbionts derived from very different soils have potentially contributed to the striking difference in the choice of symbiotic partners by Mexican and Brazilian Mimosa species. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.
-
Global patterns in endemism explained by past climatic change.
Jansson, Roland
2003-03-22
I propose that global patterns in numbers of range-restricted endemic species are caused by variation in the amplitude of climatic change occurring on time-scales of 10-100 thousand years (Milankovitch oscillations). The smaller the climatic shifts, the more probable it is that palaeoendemics survive and that diverging gene pools persist without going extinct or merging, favouring the evolution of neoendemics. Using the change in mean annual temperature since the last glacial maximum, estimated from global circulation models, I show that the higher the temperature change in an area, the fewer endemic species of mammals, birds, reptiles, amphibians and vascular plants it harbours. This relationship was robust to variation in area (for areas greater than 10(4) km2), latitudinal position, extent of former glaciation and whether or not areas are oceanic islands. Past climatic change was a better predictor of endemism than annual temperature range in all phylads except amphibians, suggesting that Rapoport's rule (i.e. species range sizes increase with latitude) is best explained by the increase in the amplitude of climatic oscillations towards the poles. Globally, endemic-rich areas are predicted to warm less in response to greenhouse-gas emissions, but the predicted warming would cause many habitats to disappear regionally, leading to species extinctions.
-
Sitagliptin reduces urinary microalbumin in experimental model of diabetic nephropathy.
Tsavdaridis, Ioannis; Papadimitriou, Dimochristos; Karanikola, Dora; Kalousis, Kostas; Katsouda, Areti; Mironidou-Tzouveleki, Maria
2015-01-01
The term Diabetic kidney disease (DKD) refers to any disease of the kidney that is a result of long-term hyperglycemia caused either by diabetes mellitus type 1 (DT1) or type 2 (DT2). When DKD coexists with macro albuminuria or proteinuria the condition is called diabetic nephropathy. DKD is the primary cause of renal failure since it is responsible for the 44% of new cases presented in the U.S.A. in 2008. Sitagliptin is an inhibitor of the enzyme dipeptidyl peptidase and is used as a treatment for diabetes since 2006. Through the inhibition of the enzyme's action sitagliptin prevents the degradation of GLP-1 which is an endogenous peptide with significant hypoglycemic actions, particularly postprandial. The proven hypoglycemic actions of sitagliptin led the researchers to further study the possible effects sitagliptin may have on the complications of diabetes mellitus such as diabetic nephropathy. The purpose of the study is to examine the effect of sitagliptin on diabetic nephropathy using biochemical parameters for assessment. 27db/db mice were used in total. They were about 4 weeks old. The mice were randomly divided into 3 groups each one consisting of 9 mice, the first 2 groups received sitagliptin treatment over a period of 32 weeks while the third did not receive any treatment. In the first group the mice received 200mg sitagliptin per Kg of body weight and in the second 10mg per Kg. At the end of the 32 weeks period the serum glucose, urea, creatinine, cholesterol, LDL, HDL, hsCRP and triglycerides as well as the urinary creatinine and microalbumin were measured in all 3 groups. The first group (received 200mg/kg) in comparison to the third group (control group) exhibited a reduction in the biochemical parameters measured: glucose -12.35% (P=0.16), urea -17.18% (P=0.61), creatinine -0.81% (P=0.95 ), cholesterol -19.28% (P=0,09), HDL -12,25% (P=0.26), LDL -31.2% (P=0.25), triglycerides -13,9% (P=0.37), hsCRP -49.8% (P=0.06), microalbumin -37.8% (P<0
-
Roncal-Jimenez, Carlos; García-Trabanino, Ramón; Barregard, Lars; Lanaspa, Miguel A; Wesseling, Catharina; Harra, Tamara; Aragón, Aurora; Grases, Felix; Jarquin, Emmanuel R; González, Marvin A; Weiss, Ilana; Glaser, Jason; Sánchez-Lozada, Laura G; Johnson, Richard J
2016-01-01
Mesoamerican nephropathy (MeN), an epidemic in Central America, is a chronic kidney disease of unknown cause. In this article, we argue that MeN may be a uric acid disorder. Individuals at risk for developing the disease are primarily male workers exposed to heat stress and physical exertion that predisposes to recurrent water and volume depletion, often accompanied by urinary concentration and acidification. Uric acid is generated during heat stress, in part consequent to nucleotide release from muscles. We hypothesize that working in the sugarcane fields may result in cyclic uricosuria in which uric acid concentrations exceed solubility, leading to the formation of dihydrate urate crystals and local injury. Consistent with this hypothesis, we present pilot data documenting the common presence of urate crystals in the urine of sugarcane workers from El Salvador. High end-of-workday urinary uric acid concentrations were common in a pilot study, particularly if urine pH was corrected to 7. Hyperuricemia may induce glomerular hypertension, whereas the increased urinary uric acid may directly injure renal tubules. Thus, MeN may result from exercise and heat stress associated with dehydration-induced hyperuricemia and uricosuria. Increased hydration with water and salt, urinary alkalinization, reduction in sugary beverage intake, and inhibitors of uric acid synthesis should be tested for disease prevention. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
-
Koukos, P K; Papadopoulou, K I; Patiaka, D T; Papagiannopoulos, A D
2000-04-01
The composition of essential oils from twigs and needles of Balkan pine (Pinus peuce Gris.) grown in northern Greece was investigated. The compounds were identified by using GC-MS analysis. The twig oil was rich in alpha-pinene (7.38%), beta-pinene (12.46%), beta-phellandrene (26.93%), beta-caryophyllene (4.48%), and citronellol (12.48%), and the needle oil was rich in alpha-pinene (23.07%), camphene (5.52%), beta-pinene (22.00%), beta-phellandrene (6.78%), bornyl acetate (9.76%), beta-caryophyllene (3.05%), and citronellol (13.42%). The mean oil yield was 2.85% for twigs and 0. 57% for needles.