Relative roles of endothelin-1 and angiotensin II in experimental post-ischaemic acute renal failure.

BACKGROUND: The relative roles of endothelin (ET)-1 and angiotensin (ANG) II in post-ischaemic acute renal failure (ARF) have not been fully established so far. With the aim of contributing to this goal, we assessed in this study the effect of ANG II and ET-1 blockade on the course of post-ischaemic-ARF. METHODS: Anaesthetized Wistar rats received i.v. either bosentan (a dual ET receptor antagonist; 10 mg/kg body weight) or losartan [ANG II type 1 (AT(1)) receptor antagonist; 5 or 10 mg/kg body weight] or both, 20 min before, during and 20 min after ischaemia. Rats in the control group received the vehicle via the same route. Survival and renal function were monitored up to 8 days after the ischaemic challenge, while haemodynamic parameters were measured 24 h after ARF. RESULTS: Our results demonstrate that bosentan treatment has a more beneficial effect on experimental ARF than losartan. The survival rate was remarkably higher in bosentan-treated rats than in both rat groups treated with losartan. In the ARF group treated with bosentan, renal blood flow (RBF) was increased by 129% in comparison with the untreated ARF group, whereas in the losartan-treated ARF groups, RBF was only approximately 35 or 38% higher than in control ARF rats. The glomerular filtration rate was markedly higher in bosentan-treated rats than in all other ARF groups on the first and second day after ischaemia. Tubular cell injury was less severe in bosentan-treated rats than in the control ARF rats, but in losartan-treated groups it was similar to that in the ARF group. Concurrent blockade of both ET and AT(1) receptors did not improve ARF because this treatment induced a marked decrease in blood pressure. CONCLUSIONS: These results suggest that ET-1 blockade is more efficient in improving the early course of post-ischaemic renal injury than ANG II inhibition, and that blockade of ET-1 might be effective in prophylaxis of ischaemic ARF.     

Multiple cerebral aneurysms

BACKGROUND: To define risk factors for the multiplicity of cerebral aneurysms, as well as clinical and therapeutical characteristics of patients with single aneurysms (SA) and multiple aneurysms (MA). METHODS: Retrospective study on 95 patients with SA and 22 patients with MA. For patients with SA and MA the following parameters were compared: gender, age, clinical state, aneurysmal localization and size, incidence of rebleeding and vasospasm, manner and outcome of treatment, preoperative interval, intraoperative rupture and postoperative complications. RESULTS: Aneurysms on anterior communicating artery existed in 37.4% of SA and in 17.8% of all MA (p < 0.05). As much as 44.2% of all aneurysms on middle cerebral artery and only 19% of all aneurysms on anterior communicating artery were associated with some other aneurysm (p < 0.02). The average size of SA was 15.4 +/- 11.8 mm, and 9.8 +/- 9 mm for MA (p < 0.05). Surgery was performed in 77.3% of patients with MA and 78.9% of patients with SA (p > 0.05), but complete surgical clipping was performed in 89.3% of patients with SA and in 47.1% of patients with MA (p < 0.01). Among operated patients with MA and SA, intraoperative rupture occurred in 36% and 17.6% of cases, respectively (p < 0.05) and ischemic postoperative complications were found in 29.4% and 17.3% of the cases (p > 0.05). Among 72.7% of all patients with MA and in 69.5% of all patients with SA the outcome was good, while among surgically treated patients it was good in 76.5% and 70.7% of cases, respectively. CONCLUSION: The treatment outcome was similar for patients with MA and SA, but complete operative treatment is significantly more frequent for SA. Multiple aneurysms were considerably smaller and with different anatomical distribution in relation to solitary aneurysms.     

A new off-pump hybrid open and endovascular repair to treat ductus Botalli and ascendens aneurysms

To report a combined ascending aorta and aortic arch hybrid repair, we performed off-pump with no aortic graft replacement. A 65-year-old man, developing progressive recurrent laryngeal nerve paralysis, underwent a computed tomography (CT) angiography detecting nonpatent residual ductus Botalli aneurysm and ascending aorta aneurysm. Due to severe multimorbidities, a less-invasive alternative was elaborated. In a first step, appropriate proximal landing zone for aortic stent grafting was achieved by ascending aorta diameter reduction, with epiaortic wrapping, and debranching the supra-aortic trunks. In the second step, endovascular stent grafts were deployed from proximal ascending aorta to descending aorta, excluding the ductus Botalli aneurysm. Six-month follow-up CT shows ductus Botalli aneurysm exclusion, stable stent graft position, and ascending diameter and patent and stenosis-free supra-aortic grafts. This case supports this alternative treatment to open aortic repair under circulatory arrest and deep hypothermia, especially in those patients considered unfit for such invasive treatment.     

Sonographic assessment of normal kidney dimensions in the first year of life—a study of 992 healthy infants

The omission of standards for renal length in infants younger than 1 year may result in a statistically significant increase in the frequency of “spurious” nephromegaly. Nonetheless, there are only a few reports specifically dealing with normal kidney dimensions in infants. Based on sonographic assessments performed on a sample of 992 healthy infants, between January 2002 and December 2004, this paper sets up standards for normal kidney dimensions in children aged 0–3 months, 3–6 months, 6–9 months, and 9–12 months and establishes correlations between kidney dimensions (length, width, and volume) and body length and weight. Linear as well as non-linear nomograms, with percentiles for all the kidney variables examined, based on body length, are provided. Also, statistically significant differences in mean values (P = 0.000) for all the observed neonatal kidney parameters, depending on gestational age at birth, are demonstrated. Principal advantages of our nomograms are that they are based on a large number of examined healthy infants and that kidney dimensions are related to body length. In addition, subjects are divided into four sub-annual age groups demonstrating gender-related differences in renal growth dynamics. Our linear nomograms are easier to use for routine clinical practice, but the percentile-based non-linear nomograms we present cover a much wider range of variations in normal infant kidney dimensions.     

Atypical presentation of distal renal tubular acidosis in two siblings

Primary distal renal tubular acidosis (dRTA) is an inherited disease characterized by the inability of the distal tubule to lower urine pH <5.50 during systemic acidosis. We report two male siblings who presented with severe hyperchloremic metabolic acidosis, high urinary pH, nephrocalcinosis, growth retardation, sensorineural hearing loss, and hypokalemic paralysis. Laboratory investigations revealed proximal tubular dysfunction (low molecular weight proteinuria, generalized hyperaminoaciduria, hypophosphatemia with hyperphosphaturia, and hypouricemia with hyperuricosuria). There was significant hyperoxaluria and laboratory evidence for mild rhabdomyolysis. Under potassium and alkali therapy, proximal tubular abnormalities, muscular enzymes, and oxaluria normalized. A homozygous mutation in the ATP6V1B1 gene, which is responsible for dRTA with early hearing loss, was detected in both siblings. In conclusion, proximal tubular dysfunction and hyperoxaluria may be found in children with dRTA and are reversible under appropriate therapy.     

Atomic interactions of neonicotinoid agonists with AChBP: molecular recognition of the distinctive electronegative pharmacophore

Acetylcholine-binding proteins (AChBPs) from mollusks are suitable structural and functional surrogates of the nicotinic acetylcholine receptors when combined with transmembrane spans of the nicotinic receptor. These proteins assemble as a pentamer with identical ACh binding sites at the subunit interfaces and show ligand specificities resembling those of the nicotinic receptor for agonists and antagonists. A subset of ligands, termed the neonicotinoids, exhibit specificity for insect nicotinic receptors and selective toxicity as insecticides. AChBPs are of neither mammalian nor insect origin and exhibit a distinctive pattern of selectivity for the neonicotinoid ligands. We define here the binding orientation and determinants of differential molecular recognition for the neonicotinoids and classical nicotinoids by estimates of kinetic and equilibrium binding parameters and crystallographic analysis. Neonicotinoid complex formation is rapid and accompanied by quenching of the AChBP tryptophan fluorescence. Comparisons of the neonicotinoids imidacloprid and thiacloprid in the binding site from Aplysia californica AChBP at 2.48 and 1.94 A in resolution reveal a single conformation of the bound ligands with four of the five sites occupied in the pentameric crystal structure. The neonicotinoid electronegative pharmacophore is nestled in an inverted direction compared with the nicotinoid cationic functionality at the subunit interfacial binding pocket. Characteristic of several agonists, loop C largely envelops the ligand, positioning aromatic side chains to interact optimally with conjugated and hydrophobic regions of the neonicotinoid. This template defines the association of interacting amino acids and their energetic contributions to the distinctive interactions of neonicotinoids.     

Freeze-frame inhibitor captures acetylcholinesterase in a unique conformation

The 1,3-dipolar cycloaddition reaction between unactivated azides and acetylenes proceeds exceedingly slowly at room temperature. However, considerable rate acceleration is observed when this reaction occurs inside the active center gorge of acetylcholinesterase (AChE) between certain azide and acetylene reactants, attached via methylene chains to specific inhibitor moieties selective for the active center and peripheral site of the enzyme. AChE catalyzes the formation of its own inhibitor in a highly selective fashion: only a single syn1-triazole regioisomer with defined substitution positions and linker distances is generated from a series of reagent combinations. Inhibition measurements revealed this syn1-triazole isomer to be the highest affinity reversible organic inhibitor of AChE with association rate constants near the diffusion limit. The corresponding anti1 isomer, not formed by the enzyme, proved to be a respectable but weaker inhibitor. The crystal structures of the syn1- and anti1-mouse AChE complexes at 2.45- to 2.65-A resolution reveal not only substantial binding contributions from the triazole moieties, but also that binding of the syn1 isomer induces large and unprecedented enzyme conformational changes not observed in the anti1 complex nor predicted from structures of the apoenzyme and complexes with the precursor reactants. Hence, the freeze-frame reaction offers both a strategically original approach for drug discovery and a means for kinetically controlled capture, as a high-affinity complex between the enzyme and its self-created inhibitor, of a highly reactive minor abundance conformer of a fluctuating protein template.     

Image Quality in Real-Time Teleultrasound of Infant Hip Exam Over Low-Bandwidth Internet Links: a Transatlantic Feasibility Study

Evolution of communication systems, especially internet-based technologies, has probably affected Radiology more than any other medical specialty. Tremendous increase in internet bandwidth has enabled a true revolution in image transmission and easy remote viewing of the static images and real-time video stream. Previous reports of real-time telesonography, such as the ones developed for emergency situations and humanitarian work, rely on high compressions of images utilized by remote sonologist to guide and supervise the unexperienced examiner. We believe that remote sonology could be also utilized in teleultrasound exam of infant hip. We tested feasibility of a low-cost teleultrasound system for infant hip and performed data analysis on the transmitted and original images. Transmission of data was accomplished with Remote Ultrasound (RU), a software package specifically designed for teleultrasound transmission through limited internet bandwidth. While image analysis of image pairs revealed statistically significant loss of information, panel evaluation failed to recognize any clinical difference between the original saved and transmitted still images.