Superhydrophobic Terrestrial Cyanobacteria and Land Plant Transition.

Plants and other organisms have evolved structures and mechanisms for colonizing land since the Early Ordovician. In this context, their surfaces, the crucial physical interface with the environment, are mainly considered barriers against water loss. It is suggested that extreme water repellency (superhydrophobicity) was an additional key innovation for the transition of algae from water to land some 400 mya. Superhydrophobicity enhances gas exchange on land and excludes aquatic competitors in water films. In a different context, in material science and surface technology, superhydrophobicity has also become one of the most important bioinspired innovations enabling the avoidance of water films and contamination. Here, we present data for an extremely water-repellent cyanobacterial biofilm of the desiccation tolerant Hassallia byssoidea providing evidence for a much earlier prokaryotic Precambrian (ca. 1-2 bya) origin of superhydrophobicity and chemical heterogeneities associated with land transition. The multicellular cyanobacterium is functionally differentiated in a submerged basal hydrophilic absorbing portion like a "rhizoid" and an upright emersed superhydrophobic "phyllocauloid" filament for assimilation, nitrogen fixation, and splash dispersed diaspores. Additional data are provided for superhydrophobic surfaces in terrestrial green algae and in virtually all ancestral land plants (Bryophytes, ferns and allies, Amborella, Nelumbo), slime molds, and fungi. Rethinking of superhydrophobicity as an essential first step for life in terrestrial environments is suggested.

Laparoscopic repositioning of a dislocated pacemaker into the rectovesical pouch.

Dislocation of the epicardial pacemaker into the peritoneal cavity is an uncommon but potentially life-threatening complication. We report a case of a 74 year old with an abdominally implanted epicardial pacemaker that migrated through the peritoneum to the excavatio rectovesicalis. The laparoscopic approach was chosen because of the increased risks of perioperative morbidity and decreased survival. The generator was implanted into a pocket beneath the anterior rectus sheath and the lead was peritonalized with a running suture. In conclusion, a laparoscopic retrieval is feasible and safe in the treatment of a displaced pacemaker in the rectovesical pouch.

Adhesion molecule expression precedes brain damages of lupus-prone mice and correlates with kidney pathology.

Central nervous system (CNS) involvement is a frequent and potentially life-threatening complication in systemic lupus erythematosus (SLE) yet the mechanisms of organ damage remain poorly understood. Upregulation of cellular adhesion molecules in kidney and other organs has been implicated in the expression of inflammation and tissue injury, but the relation between kidney pathology and altered brain function has not been studied. We therefore analyzed the expression of cellular adhesion molecules ICAM-1, VCAM-1, and E-selectin in brains from 6 to 14week old MRL/(lpr), MRL+/+ and C57BL/6 mice by real-time PCR and immunofluorescence. Adhesion molecule expression levels were compared to kidney pathology and adhesion molecule expression in the kidney. We found a significant upregulation of ICAM-1 and E-selectin mRNA in the kidneys from 14week-old MRL/(lpr) mice, which correlated with proteinuria and profound kidney damage. Moreover, despite the absence of marked brain histopathological changes, both ICAM-1 and E-selectin were also upregulated in brain tissue from these animals. There was a strong correlation of adhesion molecule expression levels in the kidney and the brain. Immunofluorescence studies revealed that ICAM-1 and E-selectin upregulation localizes to blood vessel walls, astrocytes related to the blood-brain barrier, and microglial cells. Our data indicate that cellular adhesion molecules in the brain are upregulated without evidence of overt brain damage, and that a strong relation exists with the levels of kidney damage. Therefore, brain involvement, even subclinical, should be presumed when peripheral organs are inflamed.

[Necrotizing granulomatosis with pulmonary, intestinal and renal involvement]. / Komplizierter Verlauf einer nekrotisierenden Granulomatose mit pulmonaler, intestinaler und renaler Vaskulitis.

CASE REPORT: In a 45 year old patient pulmonary, renal and ocular manifestations of ANCA-associated vasculitis is reported that required immunosuppressive therapy. On admission the patient complained about enduring lower abdominal pain. A CT scan revealed free intraabdominal fluid and dilated small intestine filled with fluid. Laparotomy was performed with the working diagnosis of paralytic ileus. Intraoperatively, hemorrhagic-necrotic alterations of the small intestinal wall were conspicuous and resected. Microscopic examination revealed transmural ischemic necrosis of the resected intestinal tissue with prominent granulomatous vasculitis of arteries. CD20-antibody rituximab was applied due to the life-threatening condition and as ultima ratio therapy. Subsequently the disease activity was controlled, renal function improved and abdominal discomfort subsided. CONCLUSION: Gastrointestinal involvement with necrotizing vasculitis is an uncommon but serious complication. Most patients respond to established therapy protocols encompassing cyclophosphamide and glucocorticoids. Administration of rituximab may be a promising alternative in refractory cases.

Radiation exposure of patient and physician during implantation and upgrade of cardiac resynchronization devices.

BACKGROUND: Cardiac resynchronization therapy (CRT) is often associated with extended fluoroscopic exposure during placement of the devices. The objective of this study was to measure the radiation exposure sustained by different parts of the body of patients and operators during fluoroscopically guided cardiac resynchronization device implantation. METHODS: Dosimetry data were prospectively recorded in a series of 104 consecutive patients, who underwent resynchronization device implantation or upgrade in our cardiac catheterization laboratory. Five Chipstrate dosimeters were fixed to the patient's skin around the thorax (right and left paravertebral, right and left parasternal, and sternal positions), one dosimeter was attached to the forehead, and one to the pubis. The operator was equipped with one dosimeter on the forehead at eye level and a ring dosimeter was worn on the right hand. RESULTS: Based on the maximum radiation dose of 9.2 mSv measured at the operator's hand in a single implantation session, it might be recommended to conservatively limit the number of implantations to four per month (an annual limit value of 500 mSv). At a mean dose of 1.2 mSv, this number can be increased sevenfold. CONCLUSION: In patients, incipient deterministic radiation effects can theoretically be observed at dose area product >400 Gy*cm(2), a dose applied in 2.9% of CRT implantation procedures. Special follow-up programs are considered necessary for these patients and for operators, as the latter may be exposed over many years given the unknown long-term impact of chronic radiation exposure and the nature of current complex electrophysiology and device procedures.

B vitamins and the risk of total mortality and cardiovascular disease in end-stage renal disease: results of a randomized controlled trial.

BACKGROUND: In observational studies, hyperhomocysteinemia has been found to be a risk factor for total mortality and cardiovascular events in patients with end-stage renal disease. These patients have grossly elevated homocysteine levels that can be lowered by supplementation with folic acid and vitamin B(12). We conducted a randomized clinical trial with B vitamins to reduce homocysteine levels and therefore cardiovascular events and total mortality. METHODS AND RESULTS: This randomized, double-blind multicenter study was conducted in 33 dialysis centers in north and east Germany between July 2002 and July 2008. We randomly assigned 650 patients with end-stage renal disease who were undergoing hemodialysis to 2 postdialysis treatments: 5 mg folic acid, 50 microg vitamin B(12), and 20 mg vitamin B(6) (active treatment) or 0.2 mg folic acid, 4 microg vitamin B(12), and 1.0 mg vitamin B(6) (placebo) given 3 times per week for an average of 2 years. The primary outcome was total mortality; the secondary outcome was fatal and nonfatal cardiovascular events. The primary outcome occurred in 102 patients (31%) receiving the active treatment and in 92 (28%) receiving placebo (hazard ratio, 1.13; 95% confidence interval, 0.85 to 1.50; P=0.51). The secondary outcome occurred in 83 patients (25%) receiving the active treatment and in 98 (30%) receiving placebo (hazard ratio, 0.80; 95% confidence interval, 0.60 to 1.07; P=0.13). CONCLUSIONS: Increased intake of folic acid, vitamin B(12), and vitamin B(6) did not reduce total mortality and had no significant effect on the risk of cardiovascular events in patients with end-stage renal disease. Clinical Trial Registration- URL: www.anzctr.org.au. Unique identifier: ACTRN12609000911291. URL: www.cochrane-renal.org. Unique identifier: CRG010600027.

Atrial fibrillation down-regulates renal neutral endopeptidase expression and induces profibrotic pathways in the kidney.

AIMS: Recent studies suggest that atrial fibrillation (AF) substantially influences microvascular flow in ventricular myocardium. This process may contribute to the occurrence of heart failure in AF. In general, development of heart failure and renal dysfunction go hand-in-hand causing systemic fluid overload and oedema. So far, it is unknown whether AF itself influences renal function. The aim of the present study was to determine the impact of AF on renal gene expression in a closed chest rapid atrial pacing model. METHODS AND RESULTS: A total of 14 pigs were studied. In five pigs, rapid atrial pacing (AT) was performed for 7 h (600 bpm); in five additional animals, rapid atrial pacing was performed in the presence of irbesartan infusion (irbesartan group). Four pigs were instrumented without interventions (sham). After the pacing period, renal expression of collagen I alpha 1 and I alpha 3, transforming growth factor-beta (TGF-beta), neutral endopeptidase (NEP; the main enzyme involved in natriuretic protein metabolism), and atrial natriuretic peptide (ANP) were determined by RT-PCR and immunoblot analysis. Functional in vitro experiments were performed using HEK-293 kidney cells. Renal mRNA expression of NEP was substantially down-regulated during AT (AT: 12.7 +/- 9.3% vs. sham: 100 +/- 43.4%; P < 0.01). Results at the mRNA level were confirmed at the protein level. Irbesartan therapy did not prevent down-regulation of NEP. In contrast, TGF-beta1 mRNA expression was up-regulated (AT: 208.5 +/- 79.3% vs. sham: 100 +/- 34.6% P< 0.05). Collagen and angiotensin II type 1 receptor (AT1R) expression were not significantly altered by AT. HEK-293 cells were used to determine the potential humoral factors involved in down-regulation of NEP. Application of aldosterone, ANP, asymmetric dimethylarginine, and angiotensin peptides failed to cause down-regulation of renal NEP expression in vitro. CONCLUSION: AT reduces NEP expression and stimulates TGF-beta1 signalling in the kidneys. Thus, even brief episodes of AT affect renal gene expression, which may account for structural renal changes and alterations of renal function in the long term.

Washout of water-soluble vitamins and of homocysteine during haemodialysis: effect of high-flux and low-flux dialyser membranes.

AIM: Vitamin deficiencies are common in patients with end-stage renal disease (ESRD) owing to dietary restrictions, drug-nutrient interactions, changes in metabolism, and vitamin losses during dialysis. The present study investigated the levels of serum and red blood cell (RBC) folate, plasma pyridoxal-5'-phosphate (PLP), serum cobalamin, blood thiamine, blood riboflavin, and plasma homocysteine (tHcy) before and after haemodialysis treatment. METHODS: Vitamin and tHcy blood concentrations were measured in 30 patients with ESRD before and after dialysis session either with low-flux (n = 15) or high-flux (n = 15) dialysers. RESULTS: After the dialysis procedure, significantly lower concentrations of serum folate (37%), plasma PLP (35%), blood thiamine (6%) and blood riboflavin (7%) were observed. No significant changes were found for serum cobalamin or for RBC folate. There were no differences in the washout of water-soluble vitamins between treatments with low-flux and high-flux membranes. Furthermore, a 41% lower concentration in tHcy was observed. The percentage decrease in tHcy was significantly greater in the patients treated with high-flux dialysers (48% vs 37%; P < 0.01). The percentage change during dialysis was significantly inversely related to the molecular weight of the vitamins measured (r =-0.867, P < 0.01). CONCLUSION: This study showed significantly lower blood or serum levels of various water-soluble vitamins after dialysis, independently of the dialyser membrane. The monitoring of the vitamin status is essential in patients treated with high-flux dialysers as well as in patients treated with low-flux dialysers.

Mitochondrial dysfunction and redox signaling in atrial tachyarrhythmia.

Accumulating evidence links calcium-overload and oxidative stress to atrial remodeling during atrial fibrillation (AF). Furthermore, atrial remodeling appears to increase atrial thrombogeneity, characterized by increased expression of adhesion molecules. The aim of this study was to assess mitochondrial dysfunction and oxidative stress-activated signal transduction (nuclear factor-kappaB [NF-kappa B], lectin-like oxidized low-density lipoprotein receptor [LOX-1], intercellular adhesion molecule-1 [ICAM-1], and hemeoxgenase-1 [HO-1]) in atrial tissue during AF. Ex vivo atrial tissue from patients with and without AF and, additionally, rapid pacing of human atrial tissue slices were used to study mitochondrial structure by electron microscopy and mitochondrial respiration. Furthermore, quantitative reverse transcription polymerase chain reaction (RT-PCR), immunoblot analyses, gel-shift assays, and enzyme-linked immunosorbent assay (ELISA) were applied to measure nuclear amounts of NF-kappa B target gene expression. Using ex vivo atrial tissue samples from patients with AF we demonstrated oxidative stress and impaired mitochondrial structure and respiration, which was accompanied by nuclear accumulation of NF-kappa B and elevated expression levels of the adhesion molecule ICAM-1 and the oxidative stress-induced markers HO-1 and LOX-1. All these changes were reproduced by rapid pacing for 24 hours of human atrial tissue slices. Furthermore, the blockade of calcium inward current with verapamil effectively prevented both the mitochondrial changes and the activation of NF-kappa B signaling and target gene expression. The latter appeared also diminished by the antioxidants apocynin and resveratrol (an inhibitor of NF-kappa B), or the angiotensin II receptor type 1 antagonist, olmesartan. This study demonstrates that calcium inward current via L-type calcium channels contributes to oxidative stress and increased expression of oxidative stress markers and adhesion molecules during cardiac tachyarrhythmia.

Diagnosis of IPA in HIV: the role of the chest X-ray and radiologist.

The role of clinical information and chest film for the discrimination between invasive pulmonary aspergillosis (IPA) and its differential diagnoses in human immunodeficiency virus (HIV) infection was studied. The diagnostic performance of clinical information and chest film alone and in combination was studied for eight internists and eight radiologists with regular exposure to IPA patients. The multicenter case sample consisted of 25 patients with proven IPA and 25 with other pulmonary diseases typical for HIV. The cases were presented on a CD-ROM. Receiver operating characteristics (ROC) methodology was employed. With clinical information alone, internists achieved the highest diagnostic performance (area under curve/AUC=0.84). Viewing the chest films did not contribute to their performance (AUC=0.80, P=0.26). The radiologist's performance on the basis of viewing the chest film (AUC=0.75) increased significantly ( P=0.012) when clinical information (AUC=0.83) was supplied. IPA cases with characteristic radiological appearance were correctly identified in 90% with chest film. For radiologists with regular exposure to HIV patients, chest films hold relevant information and contribute to the determination in cases with characteristic radiological appearance. Overall and especially in cases with less characteristic radiological appearance, they have significant profit from full access to the clinical data. For internists with regular exposure to HIV patients, chest films do not provide information essential for the verification or differentiation of potential IPA.

Age-dependent thickening of glomerular basement membrane has no major effect on glomerular hydraulic conductivity.

BACKGROUND: The effect of the increasing thickness of the glomerular basement membrane (GBM), which is seen in ageing rats, on the effective hydraulic conductivity (k) of the glomerular capillary wall was studied in Wistar rats aged 2 and 18 months. METHODS: With the use of micropuncture techniques, ultrafiltration characteristics of cortical glomeruli were determined in isolated cell-free perfused kidneys. Because the filtration fraction in this preparation is low (3%) as a consequence of high perfusion rates at glomerular filtration rates comparable with in vivo conditions, uniform ultrafiltration conditions are provided over the whole filtering surface. After fixation at a defined perfusion pressure, the surface of glomerular capillaries (S) was obtained morphometrically on light microscopic sections of the glomeruli studied previously. RESULTS: The glomerular ultrafiltration coefficient (K(f)) was 0.025 nl/s.mmHg in young rats and 0.038 nl/s.mmHg in old rats (P<0.0005) and S was 0.140 mm(2) in young and 0.244 mm(2) in old rats (P<0.0005). However, k was not significantly different (18.0 nl/s.mmHg.cm(2) in young and 15.8 nl/s.mmHg.cm(2) in old rats) despite a 2.4-fold increase of GBM thickness as estimated from electron microscopic sections. CONCLUSIONS: These findings indicate that the age-dependent increase of GBM thickness in rat kidneys did not substantially increase hydraulic resistance of the glomerular capillary wall.

Thiol-inducing and immunoregulatory effects of flavonoids in peripheral blood mononuclear cells from patients with end-stage diabetic nephropathy.

The cellular thiol status and its relationship to T-cell activation and cytokine synthesis of mononuclear cells was investigated in patients with end-stage diabetic nephropathy (ESDN) undergoing dialysis treatment. The functional effects of thiol repair by in vitro and in vivo treatment with flavonoids were elucidated. The thiol status of peripheral blood lymphocytes from 30 ESDN patients on hemodialysis and healthy controls was determined by flow cytometry. T-cell activation in response to pokeweed mitogen was analyzed by CD69 expression; cytokines were determined in cell culture supernatants. In result, compared to age-matched healthy subjects, a significant thiol deficiency in ESDN patients was obvious. The lowered total intracellular thiol levels correlated directly to a significant diminished T-cell activation and an elevated synthesis of TNF-alpha in the patient group. The treatment with flavonoids led to a restoration of the thiol status within 72 h in vitro and in vivo. This effect showed a biphasic kinetic that first utilized cell surface thiols and secondly intracellular thiols. In parallel, the T-cell activation was improved substantially along with a significant decrease in TNF-alpha release. These data provide the rational for clinical trials using flavonoids in ESDN to normalize immunoregulatory defects via restoration of the cellular thiol status.

Ambulatory treatment with intravenous norepinephrine in a patient with end stage renal disease and generalized AA amyloidosis.

A 35-year-old man with juvenile rheumatoid arthritis and generalized AA amyloidosis of 10 years duration developed end stage renal failure. Following appendectomy, the patient experienced progressive circulatory failure which required IV treatment with norepinephrine. All attempts to discontinue IV norepinephrine failed, each leading to recurrent life-threatening hypotension. Finally, a central venous port with a portable mechanical infusion pump system was implanted supplying a continuous norepinephrine infusion. The patient then became independently mobile and could be discharged. For three months, the patient was monitored as an outpatient and treated by ambulatory intermittent hemofiltration. Finally, the patient suffered from a hemorrhagic infarction of the small bowel due to postoperative adhesions and died shortly after surgery. At autopsy, advanced generalized AA amyloidosis was found. Amyloid deposits had almost entirely replaced the cortex and the medulla of the adrenal glands. It can be speculated that the requirement of exogenous norepinephrine may be in part due to an adrenal insufficiency whereas it was initially considered as being only related to cardiac involvement. A continuous ambulatory treatment with catecholamines could be a possible treatment - at least temporarily - in amyloid cases in which all other attempts have failed to prevent chronic life-threatening hypotension.

Small-sized low-density lipoproteins of subclass B from patients with end-stage renal disease effectively augment tumor necrosis factor-alpha-induced adhesive properties in human endothelial cells.

Increased prevalence of small-sized low-density lipoprotein (LDL) subclass B (diameter < 25.5 nm) possibly is involved in the multifactorial process of cardiovascular disease in patients with end-stage renal disease. Given these epidemiological observations, mechanisms underlying the combined effect of a proinflammatory insult and LDL of different subclasses (subclass A, diameter > 25.5 nm, and subclass B) in a cellular model were investigated. For this, human umbilical vein endothelial cells were preexposed to LDL, then stimulated with tumor necrosis factor-alpha (TNF-alpha). Modulatory effects of LDL phenotypes on the activation of adhesion molecules, monocyte adherence, and transcriptional activity of nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) were investigated. Our data show that subclass B LDLs were metabolized through nonspecific scavenger receptors and specific LDL-receptor pathways in endothelial cells. Furthermore, LDL subclass B in comparison to subclass A more effectively enhanced monocyte recruitment and adhesive properties of endothelial cells in response to TNF-alpha. These effects appeared not to be mediated by oxidative stress-responsive NF-kappaB because modulation of this transcription factor by LDL was moderate and similar for both LDL phenotypes. Conversely, effects of LDL subclass B were considered to be caused by augmented AP-1 binding activity. In conclusion, the present model provides new clues in atherogenic mechanisms of small-sized LDLs, which sensitize vascular cells to inflammatory signals more effectively than normal-sized LDLs.

Guideline based structured documentation: the final goal?

Structured documentation of medical procedures facilitates information retrieval for research and therapy and may help to improve patient care. Most medical documents until today however consist mainly of unstructured narrative text. Here we present an application for endoscopy which is not only fully integrated into a comprehensive clinical information system, but which also supports various degrees of structuring examination reports. The application is used routinely in a German University hospital since summer 2000. We present the first unstructured version which permits storage of a free text report together with selected examination images. The next step added improved structure to the document using a catalogue of index terms. The practical advantages of selective patient retrieval are described. Today we use a version which supports fully structured, guideline based documentation of endoscopy reports in order to automatically generate essential classification codes and the narrative examination report All versions have advantages and disadvantages and we conclude that guideline based documentation may not be suitable for all endoscopy cases.