1991 - The year Punk broke

1991 begleitete der Regisseur Dave Markey die Bands Sonic Youth und Nirvana, damals noch eher unbekannte Underground-Bands, auf ihrer Tour durch Europa. Wer jetzt allerdings eine objektive Dokumentation erwartet, die intime Einblicke in das Bandleben und das Leben als Musiker gewährt, wird bei der Sichtung von 1991 – THE YEAR PUNK BROKE enttäuscht werden. Obwohl der Film dem Titel nach das Ende der Punk-Ära verkündet und somit versucht, sich in einen größeren Zusammenhang mit der Musikszene zu setzen, zeigt sich dies im Verlauf des Films eher als zufälliges Nebenprodukt denn als konkretes künstlerisches Anliegen. Der Film erweist sich eher als en passant bei einer Tournee entstandenes Nebenprodukt – man stecke ein paar überdrehte Rockmusiker zusammen und gebe ihnen eine Kamera; das Ergebnis veröffentliche man ein Jahr später (in diesem Fall 1992 auf VHS). Prinzipiell ließe sich durch eine solche Aufnahmeform ein durchaus authentisches Bild des Touralltags zeigen. Allerdings verfährt Markey nicht nach dem Prinzip des direct cinema, in dem die Kamera zum stillen Begleiter der Handlung wird. Die Kamera ist vielmehr immer präsent und lädt die Musiker zur Interaktion mit ihr ein. Beispielsweise begibt sich Thurston Moore, Frontman von Sonic Youth, mit einem Mikrofon bewaffnet auf die Suche nach hilflosen, gerne des Englischen nicht mächtigen Interviewpartnern und verwickelt sie in einigermaßen sinnlose Gespräche. Dass sich diese Szenen auch ohne Beisein der Kamera abgespielt hätten, ist zu bezweifeln

Novel potential interacting partners of fibronectin in spontaneous animal model of interstitial cystitis

Feline idiopathic cystitis (FIC) is the only spontaneous animal model for human interstitial cystitis (IC), as both possess a distinctive chronical and relapsing character. Underlying pathomechanisms of both diseases are not clearly established yet. We recently detected increased urine fibronectin levels in FIC cases. The purpose of this study was to gain further insight into the pathogenesis by assessing interacting partners of fibronectin in urine of FIC affected cats. Several candidate proteins were identified via immunoprecipitation and mass spectrometry. Considerable changes in FIC conditions compared to physiological expression of co-purified proteins were detected by Western blot and immunohistochemistry. Compared to controls, complement C4a and thioredoxin were present in higher levels in urine of FIC patients whereas loss of signal intensity was detected in FIC affected tissue. Galectin-7 was exclusively detected in urine of FIC cats, pointing to an important role of this molecule in FIC pathogenesis. Moderate physiological signal intensity of galectin-7 in transitional epithelium shifted to distinct expression in transitional epithelium under pathophysiological conditions. I-FABP expression was reduced in urine and urinary bladder tissue of FIC cats. Additionally, transduction molecules of thioredoxin, NF-κB p65 and p38 MAPK, were examined. In FIC affected tissue, colocalization of thioredoxin and NF-κB p65 could be demonstrated compared to absent coexpression of thioredoxin and p38 MAPK. These considerable changes in expression level and pattern point to an important role for co-purified proteins of fibronectin and thioredoxin-regulated signal transduction pathways in FIC pathogenesis. These results could provide a promising starting point for novel therapeutic approaches in the future

Renal AA-amyloidosis in intravenous drug users - a role for HIV-infection?

Background: Chronic renal disease is a serious complication of long-term intravenous drug use (IVDU). Recent reports have postulated a changing pattern of underlying nephropathy over the last decades. Methods: Retrospective investigation including all patients with prior or present IVDU that underwent renal biopsy because of chronic kidney disease between 01.04.2002 and 31.03.2012 in the city of Frankfurt/Main, Germany. Results: Twenty four patients with IVDU underwent renal biopsy because of progressive chronic kidney disease or proteinuria. Renal AA-amyloidosis was the predominant cause of renal failure in 50% of patients. Membranoproliferative glomerulonephritis (GN) was the second most common cause found in 21%. Patients with AA-amyloidosis were more likely to be HIV infected (67 vs.17%; p=0.036) and tended to have a higher rate of repeated systemic infections (92 vs. 50%; p=0.069). Patients with AA-amyloidosis presented with progressive renal disease and nephrotic-range proteinuria but most patients had no peripheral edema or systemic hypertension. Development of proteinuria preceded the decline of GFR for approximately 1--2 years. Conclusions: AA-amyloidosis was the predominant cause of progressive renal disease in the last 10 years in patients with IVDU. The highest rate of AA-amyloidosis observed was seen in HIV infected patients with IVDU. We speculate that chronic HIV-infection as well as the associated immunosuppression might promote development of AA-amyloidosis by increasing frequency and duration of infections acquired by IVDU

Activation of Rac-1 and RhoA contributes to podocyte injury in chronic kidney disease

Rho-family GTPases like RhoA and Rac-1 are potent regulators of cellular signaling that control gene expression, migration and inflammation. Activation of Rho-GTPases has been linked to podocyte dysfunction, a feature of chronic kidney diseases (CKD). We investigated the effect of Rac-1 and Rho kinase (ROCK) inhibition on progressive renal failure in mice and studied the underlying mechanisms in podocytes. SV129 mice were subjected to 5/6-nephrectomy which resulted in arterial hypertension and albuminuria. Subgroups of animals were treated with the Rac-1 inhibitor EHT1846, the ROCK inhibitor SAR407899 and the ACE inhibitor Ramipril. Only Ramipril reduced hypertension. In contrast, all inhibitors markedly attenuated albumin excretion as well as glomerular and tubulo-interstitial damage. The combination of SAR407899 and Ramipril was more effective in preventing albuminuria than Ramipril alone. To study the involved mechanisms, podocytes were cultured from SV129 mice and exposed to static stretch in the Flexcell device. This activated RhoA and Rac-1 and led via TGFβ to apoptosis and a switch of the cells into a more mesenchymal phenotype, as evident from loss of WT-1 and nephrin and induction of α-SMA and fibronectin expression. Rac-1 and ROCK inhibition as well as blockade of TGFβ dramatically attenuated all these responses. This suggests that Rac-1 and RhoA are mediators of podocyte dysfunction in CKD. Inhibition of Rho-GTPases may be a novel approach for the treatment of CKD

High-Dose Enalapril Treatment Reverses Myocardial Fibrosis in Experimental Uremic Cardiomyopathy

AIMS: Patients with renal failure develop cardiovascular alterations which contribute to the higher rate of cardiac death. Blockade of the renin angiotensin system ameliorates the development of such changes. It is unclear, however, to what extent ACE-inhibitors can also reverse existing cardiovascular alterations. Therefore, we investigated the effect of high dose enalapril treatment on these alterations. METHODS: Male Sprague Dawley rats underwent subtotal nephrectomy (SNX, n = 34) or sham operation (sham, n = 39). Eight weeks after surgery, rats were sacrificed or allocated to treatment with either high-dose enalapril, combination of furosemide/dihydralazine or solvent for 4 weeks. Heart and aorta were evaluated using morphometry, stereological techniques and TaqMan PCR. RESULTS: After 8 and 12 weeks systolic blood pressure, albumin excretion, and left ventricular weight were significantly higher in untreated SNX compared to sham. Twelve weeks after SNX a significantly higher volume density of cardiac interstitial tissue (2.57±0.43% in SNX vs 1.50±0.43% in sham, p<0.05) and a significantly lower capillary length density (4532±355 mm/mm(3) in SNX vs 5023±624 mm/mm(3) in sham, p<0.05) were found. Treatment of SNX with enalapril from week 8-12 significantly improved myocardial fibrosis (1.63±0.25%, p<0.05), but not capillary reduction (3908±486 mm/mm(3)) or increased intercapillary distance. In contrast, alternative antihypertensive treatment showed no such effect. Significantly increased media thickness together with decreased vascular smooth muscles cell number and a disarray of elastic fibres were found in the aorta of SNX animals compared to sham. Both antihypertensive treatments failed to cause complete regression of these alterations. CONCLUSIONS: The study indicates that high dose ACE-I treatment causes partial, but not complete, reversal of cardiovascular changes in SNX

Endothelin receptor antagonists influence cardiovascular morphology in uremic rats

Endothelin receptor antagonists influence cardiovascular morphology in uremic rats.BackgroundIt is generally held that renal failure results in blood pressure (BP)-independent structural changes of the myocardium and the vasculature. The contribution, if any, of endothelin (ET) to these changes has been unknown.MethodsWe morphometrically studied random samples of the left ventricle myocardium and small intramyocardial arteries in subtotally (5/6) nephrectomized (SNx) male Sprague-Dawley rats treated with either the selective ETA receptor antagonist BMS182874 (30mg/kg/day) or the nonselective ETA/ETB receptor antagonist Ro46-2005 (30mg/kg/day) in comparison with either sham-operated rats, untreated SNx, or SNx rats treated with the angiotensin-converting enzyme inhibitor trandolapril (0.1mg/kg/day).ResultsEight weeks later, systolic BP was lower in trandolapril-treated SNx compared with untreated SNx animals. No decrease in BP was seen following either ET receptor antagonist at the dose used. A significantly increased volume density of the myocardial interstitium was found in untreated SNx rats as compared with sham-operated controls. Such interstitial expansion was prevented by trandolapril and either ET receptor antagonist. SNx caused a substantial increase in the wall thickness of small intramyocardial arteries. The increase was prevented by trandolapril or BMS182874 treatment. The arteriolar wall:lumen ratio was significantly lower in all treated groups when compared with untreated SNx. In contrast, only trandolapril, but not the ET receptor antagonists, attenuated thickening of the aortic media in SNx animals.ConclusionsThe ETA-selective and ETA/ETB-nonselective receptor antagonists appear to prevent development of myocardial fibrosis and structural changes of small intramyocardial arteries in experimental chronic renal failure. This effect is independent of systemic BP

Grundlagen der Nierenpathologie für Pathologen – Teil 2 : Nichtentzündliche Veränderungen

Zusammenfassung: Die Nierenbiopsiediagnostik bei medizinisch indizierten Biopsien und Nierentransplantatbiopsien wird überwiegend in Zentren mit ausgebildeten Nephropathologen betrieben. Veränderungen im nichtneoplastischen Nierenparenchym bei tumorbedingten Nephrektomien, insbesondere nichtentzündliche, ischämisch und vaskulär bedingte Veränderungen oder diabetische Nephropathie, können bei Patienten mit lokalisiertem Nierenkarzinomen und gutem tumorassoziiertem Überleben prognostisch von größerer Bedeutung sein als das Tumorleiden an sich. In diesem Teil zu den Grundlagen der Nierenpathologie für Pathologen sollen die häufigsten nichtentzündlichen Nierenerkrankungen im vaskulären, glomerulären und tubulointerstitiellen Kompartiment beleuchtet werden. Abstract: The evaluation of kidney biopsies for specific renal diseases or kidney transplant biopsies is mainly restricted to specialized centers. Lesions in nonneoplastic renal tissue in partial nephrectomies or nephrectomies due to renal tumors, especially noninflammatory, ischemic, vascular changes or diabetic nephropathy can be of greater prognostic significance than the tumor itself in patients with a localized tumor and good tumor-associated survival. In this part of basic nephropathology for pathologists, the most common noninflammatory lesions of the vascular, glomerular and tubulo-interstitial compartment are discussed

Incidental Monotypic (Fat-Poor) Renal Angiomyolipoma Diagnosed by Core Needle Biopsy

We present the case of a 55-year-old patient with a history of chemotherapy and bone marrow transplantation because of acute myeloid leukaemia. An incidental 4 × 3 cm measuring renal mass was detected while performing a magnetic resonance imaging (MRI) for lumbago. The lesion was suspected to be either a renal cell carcinoma (RCC) or a leukemic infiltration. To decide about further treatment a percutaneous core needle biopsy was performed. Histology showed a monotypic angiomyolipoma, a relatively rare benign renal lesion. Interestingly, in cross-sectional imaging, angiomyolipoma was not taken into differential diagnostic account because of lack of a fatty component. Due to bleeding after biopsy the feeding artery of the tumor was occluded by microcoils. This case demonstrates the utility of biopsy of renal tumors, in particular when small tumor-like lesions are incidentally detected to decide about the right treatment and thereby avoiding nephrectomy

Lack of Intestinal Epithelial Atg7 Affects Paneth Cell Granule Formation but Does Not Compromise Immune Homeostasis in the Gut

Genetic polymorphisms of autophagy-related genes have been associated with an increased risk to develop inflammatory bowel disease (IBD). Autophagy is an elementary process participating in several cellular events such as cellular clearance and nonapoptotic programmed cell death. Furthermore, autophagy may be involved in intestinal immune homeostasis due to its participation in the digestion of intracellular pathogens and in antigen presentation. In the present study, the role of autophagy in the intestinal epithelial layer was investigated. The intestinal epithelium is essential to maintain gut homeostasis, and defects within this barrier have been associated with the pathogenesis of IBD. Therefore, mice with intestinal epithelial deletion of Atg7 were generated and investigated in different mouse models. Knockout mice showed reduced size of granules and decreased levels of lysozyme in Paneth cells. However, this was dispensable for gut immune homeostasis and had no effect on susceptibility in mouse models of experimentally induced colitis

Case Report: Pediatric Renal Sarcoidosis and Prognostic Factors in Reviewed Cases

Background: Pediatric sarcoidosis is a complex inflammatory disorder with multisystemic manifestations. Kidney involvement in children is rare, and prognostic factors are unknown. Case Report and Methods: We report the case of a 16-year-old girl with multiorgan sarcoidosis and renal involvement. The patient presented with tubulointerstitial nephritis, acute kidney injury (AKI), chest CT disseminated noduli, granulomatous iridocyclitis, giant-cell sialadenitis, and arthralgia. The kidney biopsy revealed non-granulomatous interstitial nephritis. Treatment consisted of initial high-dose methylprednisolone pulse followed by oral prednisolone and methotrexate. Full remission was achieved. In addition, we performed a literature review using PubMed and analyzed data on pediatric renal sarcoidosis cases. Results: We identified 36 cases of pediatric sarcoidosis with renal involvement on presentation and data on the end-of-follow-up glomerular filtration rate (GFR). The data from the literature review showed that renal involvement was slightly more prevalent in males (60%). AKI was present in most of the described patients (84%). Oral prednisolone was used in 35 of 36 cases; in more severe cases, other immunosuppressants were used. We newly identified renal concentration impairment and granulomatous interstitial nephritis as factors with a clear trend toward GFR loss at the end of follow-up, emphasizing the importance of kidney biopsy in symptomatic patients. In contrast, higher GFR at presentation and hypercalcemia were rather favorable factors. According to the identified predictive factors, our patient has a good prognosis and is in remission. Conclusion: The factors indicating a trend toward an unfavorable renal outcome in pediatric sarcoidosis are renal concentration impairment and granulomatous interstitial nephritis at presentation, while a higher GFR is beneficial