(C) 2009 IBRO Published by Elsevier Ltd All rights reserved “

(C) 2009 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Purpose:

Extracorporeal. shock wave lithotripsy is the preferred treatment for upper urinary tract renal calculi. However, this treatment is associated with a high rate of recurrent renal calculi. Shock wave therapy can result in renal epithelial cell injury, which in turn is a most important factor in calculus formation. We investigated the influence of kidney damage secondary to shock waves on Ca oxalate crystal retention in the kidney. Materials and

Methods: AG-120 A total of 32 rats were randomly divided into 4 groups, including group 1-controls, group 2-sham. treated rats given 25 ml 0.75% ethylene glycol per day for 14 days, group 3-rats given 15 kV 1Hz shock waves 500 times to the

left kidney, followed by 25 ml 0.75% ethylene glycol daily for 14 days, and group 4-rats with the same treatment as group 3 except the number of impacts was increased to 1,000. The 2 kidneys were removed at the end of the experiment. Ca oxalate crystals were observed by surgical microscopy in kidney sections stained with hematoxylin and eosin. Crystal morphology was determined using polarizing microscopy. Acidified kidney tissue homogenate was examined for Ca and oxalate content by colorimetry (Sigma (R)).

Results: Kidney sections showed that kidneys that did not receive shock waves had fewer crystals than kidneys with shock Idasanutlin solubility dmso waves, which had crystals in major areas. In the left kidney in groups 2 to 4 the mean SD quantity of Ca was 16.88 +/- 6.41, 28.58 +/- 7.54 and 40.81 +/- 15.29 mu mol/gm wet kidney and the mean quantity of oxalate was 8.44 +/- 6.80, 20.52 +/- 7.70, 31.76 +/- 14.14 mu mol/gm wet kidney, respectively. Ca oxalate density increased with the number of shock wave impacts.

Conclusions: Kidney damage caused by shock wave treatment can increase Ca oxalate crystal retention

in the kidneys of rats in this stone Obeticholic Acid datasheet model.”
“Orexin-A, synthesized by neurons of the lateral hypothalamus helps to maintain wakefulness through excitatory projections to nuclei involved in arousal. Obvious changes in eye movements, eyelid position and pupil reactions seen in the transition to sleep led to the investigation of orexin-A projections to visuomotor cell groups to determine whether direct pathways exist that may modify visuomotor behaviors during the sleep-wake cycle. Histological markers were used to define these specific visuomotor cell groups in monkey brainstem sections and combined with orexin-A immunostaining. The dense supply by orexin-A boutons around adjacent neurons in the dorsal raphe nucleus served as a control standard for a strong orexin-A input.

With limited reports in the literature, the risk of acute hemorrh

With limited reports in the literature, the risk of acute hemorrhage associated with these lesions is poorly understood.

METHODS:

A 39-year-old man presented with paraplegia and bilateral upper-extremity weakness related to an acute intramedullary hemorrhage from a thoracic spinal hemangioblastoma. Magnetic resonance imaging revealed an intramedullary hemorrhage from T3 to T6 with prominent flow voids along the dorsal aspect of the spinal cord from T6 to T10. Magnetic resonance angiography of the thoracic spine indicated a prominent enhancing vessel along the dorsum of the thoracic cord.

RESULTS: An emergency T3 to T8 laminoplasty was performed for evacuation of the hematoma and gross see more total resection of the lesion. Pathological analysis of the tumor biopsy confirmed the diagnosis of hemangioblastoma.

CONCLUSION: The risk of spontaneous Foretinib order hemorrhage from a spinal hemangioblastoma is low. Spinal

hemangioblastomas presenting with intramedullary hemorrhage tend to cause severe neurological deficits and have a poorer long-term prognosis compared with subarachnoid hemorrhage and nonhemorrhagic lesions.”
“Purpose: Hypersensitivity to visceral stimuli in interstitial cystitis/painful bladder syndrome may result from enhanced responsiveness of affective circuits (including the amygdala complex) and associated central pain amplification. Potentiation of the eyeblink startle reflex under threat is mediated by output from the amygdala complex and, therefore, represents a noninvasive marker to study group differences in responsiveness in this brain circuit.

Materials and

Methods: Acoustic startle responses were examined in female patients with interstitial cystitis/painful PD184352 (CI-1040) bladder syndrome (13) and healthy controls (16) during context threat (application of muscle stimulation electrodes to the lower abdomen overlying the bladder), and cued conditions for safety (no stimulation possible), anticipation and imminent threat of aversive abdominal stimulation over the bladder.

Results: Patients showed significantly greater startle responses during nonimminent threat conditions (baseline, safe and anticipation periods) while both groups showed similar robust startle potentiation during the imminent threat condition. Higher rates of anxiety and depression symptoms in the patient group did not account for the group differences in startle reflex magnitude.

Conclusions: Compared to controls, female patients with interstitial cystitis/painful bladder syndrome showed increased activation of a defensive emotional circuit in the context of a threat of abdominal pain. This pattern is similar to that previously reported in patients with anxiety disorders as well as those with irritable bowel syndrome.

Exposure can lead to changes in animal physiology and behavior an

Exposure can lead to changes in animal physiology and behavior and has been demonstrated in both experimental and field analyses. There are also potential risks to high trophic level predators, including humans. A maternal transfer has been demonstrated in fish as PCBs bind to lipids in eggs. In this study, behavioral traits (exploration and free swimming, with or without challenges) of contaminated zebrafish (Danio rerio)

LXH254 chemical structure adults and their offspring (both as five-day-old larvae and as two-month-old fish reared under standard conditions) were measured using video-tracking. Long-term dietary exposure to a mixture of non-coplanar PCBs was used to mimic known environmental contamination levels and congener composition. Eight-week-old fish were exposed for eight months at 26-28 degrees C. Those exposed to an intermediate dose (equivalent to that found in the Loire Estuary, Sigma(CB) = 515 ng g(-1) dry weight in food) displayed behavioral disruption in exploration capacities. Fish exposed to the highest dose (equivalent to that found in the Seine Estuary, Sigma(CB) = 2302 ng g(-1), dry weight in food) displayed an increased swimming activity at

the end of the night. In offspring, larval activity was increased and two-month-old fish occupied the bottom section of the tank less often. These findings call for more long-term experiments using the zebrafish model; the mechanisms underlying behavioral disruptions need to be understood due to their implications for both Selleckchem Tozasertib human health and their ecological relevance in terms of individual fitness and survival. (C) 2013 Elsevier Inc. All rights reserved.”
“Prerenal acute kidney injury (AKI) is thought to be a reversible loss of renal function without structural damage. Although prerenal and intrinsic AKI frequently coexist in clinical situations, serum creatinine and urine output provide no information to support their differentiation. Recently developed biomarkers reflect tubular epithelial injury; therefore, we evaluated urinary biomarker levels in an

adult mixed intensive care unit (ICU) cohort of patients who had ADAM7 been clinically evaluated as having prerenal AKI. Urinary L-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), N-acetyl-beta-D-glucosaminidase (NAG), and albumin in patients with prerenal AKI showed modest but significantly higher concentrations than in patients with non-AKI. We also conducted a proof-of-concept experiment to measure urinary biomarker excretion in prerenal AKI caused by volume depletion. Compared with cisplatinum and ischemia-reperfusion models in mice, volume depletion in mice caused a modest secretion of L-FABP and NGAL into urine with more sensitive response of L-FABP than that of NGAL.

We determined the mRNA expression levels of the EMP1 gene in peri

We determined the mRNA expression levels of the EMP1 gene in peripheral-blood leukocytes of patients and control subjects (n = 27 each). Next, we performed case-control association analyses (MDD, n = 182: controls, n = 350) in the Japanese population. The level of expression of the EMP1 mRNA was significantly lower in medication-free patients compared with control subjects (P<0.001). The association Ruboxistaurin molecular weight analysis revealed an absence of association between the polymorphisms studied and MDD, whereas a gender-specific association was observed between male controls

and male patients for marker rs7315725 (permutation P = 0.039). Our results suggest that the EMP1 gene may be implicated in the pathophysiology of MDD in the Japanese population. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“Objective: To establish associations between kg strength and mortality in men and women with lower extremity peripheral arterial disease (PAD).

Methods: This was an observational, prospective study of 410 men and women with PAD aged 55 and older recruited from Chicago-area medical centers and followed for a selleckchem mean of 60 months. The participants were followed for a mean of 60.0 months. Isometric knee extension, knee flexion, hip extension, and hip flexion were measured at baseline. Primary outcomes were all-cause and cardiovascular disease mortality. Cox proportional hazards models were used to assess relations between

leg strength and all-cause and cardiovascular disease mortality among men and women, adjusting for age, race, comorbidities, physical activity, smoking, body mass index, and the ankle brachial index.

Results- Among the 246 male participants, poorer baseline strength for knee flexion (P trend =.029), knee extension (P trend = .010), and hip extension (P trend =.013) were each associated Obatoclax Mesylate (GX15-070) independently with higher all-cause mortality. Poorer strength for knee flexion (P trend = .042) and hip extension (P trend =.029) were associated

with higher cardiovascular mortality. Compared with those in the fourth (best) baseline knee flexion quartile, hazard ratios for all-cause and cardiovascular disease mortality among men in the first (poorest) knee flexion quartile were 2.23 (95% confidence interval [CI], 102-4.87; P = .045) and 4.20 (95% Cl, 1.12-15.79; P =.044), respectively. No significant associations of leg strength and all-cause mortality were identified among women.

Conclusions: Poorer leg strength is associated with increased mortality in men, but not women, with PAD. Future study is needed to determine whether interventions that increase leg strength improve survival in men with PAD. (J Vase Surg 2010;52:624-31.)”
“Previous human imaging studies used facial stimuli to explore the potential association between depression and fear. This study aimed at investigating brain alterations in a rodent model of depression when innate fear was induced in the form of the predator odor trimethylthiazoline (TMT).

Therefore, the present study was designed to test whether a metab

Therefore, the present study was designed to test whether a metabotropic glutamate (mGlu) receptor subtype also coupled to G(q/11)-proteins, the mGlu5 receptor, also induces EPSCs when recording from layer V cortical pyramidal cells of the rat medial prefrontal cortex (mPFC). The mGlu1/5 receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG) induces EPSCs at a

similar frequency as a near-maximally effective 5-HT concentration. The mGlu5 receptor negative allosteric modulator 2-methyl-6-(phenylethynyl)pyridine (MPEP, 300 nM) potently blocked DHPG-induced EPSCs. Previous work has suggested that activation of 5-HT2A see more and OX2 receptors induces glutamate release, while mGlu2, mGlu4, and mGlu8 receptor activation suppress transmitter release from thalamocortical terminals. Taken together with past results, these findings suggest that mGlu2, mGlu4, mGlu5 and mGlu8 may all act to modulate glutamate release from afferents impinging on layer V pyramidal cells of the mPFC. These findings further suggest that monoamines, neuropeptides and glutamate itself all enhance the excitability of prefrontal cortical output cells indirectly via modulation

of glutamate release. (c) 2008 Elsevier Ireland Ltd. All rights reserved.”
“Both NMDA and non-NMDA receptors AZD4547 in vitro participate in the consolidation of passive avoidance learning (PAL) in the day-old chick. NMDA antagonists have also been implicated in reconsolidation processes following reminder-trials. In this study, we examined the effect of administering 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA receptor antagonist, on reconsolidation following memory reactivation. New Hampshire x White leghorn cockerels were trained using a modified version Tangeritin of the PAL task. When CNQX was administered 20 min following a reminder trial, a retention deficit was detected at 90 min, but this had resolved by 24 h following the reminder. The parameters of the reconsolidation deficit were similar

to those induced by CNQX injections post-training with the exception of their transience. This finding suggests that the action of non-NMDA receptors may perform a similar role in both consolidation and reconsolidation processes. (c) 2008 Elsevier Ireland Ltd. All rights reserved.”
“The doublecortin (DCX) protein is associated with microtubules, and is essential for neuronal migration, differentiation, and plasticity. In mammals, it is expressed in developing neurons and new immature neuroblasts in the adult brain, but not generally in mature neurons. In the retina, doublecortin is detectable as early as embryonic day 15 (E15), is highly expressed between E18 and E20, and is poorly expressed postnatally. In this study, we investigated immunohistochemically the expression and cellular localization of doublecortin in the adult rat retina. Doublecortin was expressed in the outer plexiform layer (OPL), and in cells in the outer border of the inner nuclear layer (INL). No other layers were labeled by anti-doublecortin antibodies.

Furthermore, nonconserved substitutions of Asp(632) significantly

Furthermore, nonconserved substitutions of Asp(632) significantly reduced the potency of C34 to sequestrate six-helix bundle formation and to inhibit HIV-1-mediated cell-cell fusion and infection, suggesting its importance for designing antiviral fusion inhibitors. Taken together, these data suggest that the salt bridge between the N- and C-terminal heptad repeat regions of the fusion-active HIV-1 gp41 core structure is critical for viral entry and inhibition.”
“Suppression of peri-infarct Selleck Paclitaxel depolarizations (PIDs) is one

of the major mechanisms of hypothermic protection against transient focal cerebral ischemia. Previous studies have shown the lack of hypothermic protection against permanent focal ischemia. We hypothesized the lack of hypothermic protection was due to the poor efficacy in suppression of PIDs. To examine the

hypothesis, we elucidated the effects of hypothermia on the manner of propagation of PIDs with temporal and spatial resolutions using NADH (reduced nicotinamide adenine dinucleotide) fluorescence images by illuminating the parietal-temporal cortex with ultraviolet light. Spontaneously hypertensive rats (n=14) were subjected to permanent focal ischemia by occlusion AZD8055 nmr of the middle cerebral and left common carotid arteries. 2-h hypothermia (30 degrees C) was initiated before ischemia. Although Evodiamine hypothermia delayed the appearance of PIDs, it did not suppress their appearance. Furthermore, 54% of the PIDs enlarged the high-intensity area of NADH fluorescence in the hypothermia group, similar to the normothermia group (53%). The high-intensity area of NADH

fluorescence widened by each PID was larger in the hypothermia group than in the normothermia group. These findings suggest that PIDs even in hypothermia are one of the major factors causing growth of infarction, emphasizing the importance of therapy that targets suppression of PIDs even during hypothermia. (C) 2008 Elsevier Ireland Ltd. All rights reserved.”
“TRIM5 alpha has been shown to be a major postentry determinant of the host range for gammaretroviruses and lentiviruses and, more recently, spumaviruses. However, the restrictive potential of TRIM5 alpha against other retroviruses has been largely unexplored. We sought to determine whether or not Mason-Pfizer monkey virus (M-PMV), a prototype betaretrovirus isolated from rhesus macaques, was sensitive to restriction by TRIM5 alpha. Cell lines from both Old World and New World primate species were screened for their susceptibility to infection by vesicular stomatitis virus G protein pseudotyped M-PMV. All of the cell lines tested that were established from Old World primates were found to be susceptible to M-PMV infection.

Previously, we showed that most parvalbumin positive cells in the

Previously, we showed that most parvalbumin positive cells in the external plexiform layer (EPL) of the mouse main olfactory CUDC-907 cell line bulb (MOB) were anaxonic but displayed some patch-like beta IV-spectrin and sodium channel cluster positive segments on their dendrites. In this study we further characterized those particular dendritic segments. AnkyrinG was also located there, whereas phospho-I kappa B alpha was not. Electron-microscopically those dendritic segments displayed

the membrane undercoating characteristic to the AlSs and nodes of Ranvier, further confirming their resemblance to the spike generation sites, “”hot spots”". Three-dimensional analysis revealed that each parvalbumin positive EPL neuron had 2-7 hot spots, 3-28 mu m in length and located 7-50 mu m from the somata. Similar “”hot spots”" were also encountered on a few calretinin positive granule cells and nitric oxide synthase positive periglomerular cells in the mouse MOB. In addition parvalbumin positive EPL cells in the Fat MOB displayed similar multiple dendritic “”hot spots”". Our study suggested that these morphologically identified dendritic “”hot spots”" might correspond to dendritic spike generation sites of those neurons. (C) 2008 Elsevier Ireland Ltd and the Japan Neuroscience Society.

check details All rights reserved.”
“Aims: Plasmids are critical for the pathogenicity of Yersinia pestis. In order to carry out a systematic investigation of their role in pathogenesis, we cured plasmids from Y. pestis.

Methods and Results: Each plasmid’s replicon of Y. pestis was cloned into plasmid pEX18Gm containing a counter-selectable sacB gene, and was then introduced into

Y. pestis strain 201 by electroporation. Strains containing recombinant Erythromycin plasmids were cultivated under antibiotic selection. The resultant plasmid-curing colonies, identified by specific polymerase chain reactions, were then cured off pEX18Gm under sucrose pressure. This method was used to successfully cure all four plasmids of Y. pestis, singly or in different combinations.

Conclusions: Naturally evolving plasmids in Y. pestis are difficult to remove by conventional curing methods. We employed a method based on plasmid incompatibility to cure the plasmids from Y. pestis, which confirmed the efficacy of this method for curing plasmids with different types of replicons from one bacterium.

Significance and Impact of the Study: There have been no reports on the curing of multiple plasmids by using replication mechanisms from one bacterium with this technique. In the present study, we were able to successfully apply this methodology to cure four plasmids from Y. pestis, confirming its feasibility.”
“Prepulse inhibition (PPI) and habituation of the acoustic startle reflex (ASR) are considered to be candidate endophenotypes of schizophrenia.

This analysis detected extensive clonal expansion of

hepa

This analysis detected extensive clonal expansion of

hepatocytes, as previously found in chronically infected chimpanzees and woodchucks. Tissue sections were stained with hematoxylin and eosin (H&E), and DNA was extracted from the adjacent section for inverse PCR to detect integrated HBV DNA. This analysis revealed that clonal expansion can occur among normal-appearing human hepatocytes.”
“The Etomoxir research buy study investigates time-variant directed interactions between brain regions during the interburst-burst EEG pattern (trace alternant) characteristic of quiet sleep in healthy neonates. The transition from interburst to burst is of particular interest as the generation of the EEG characteristics at burst onset reflects timing and time-variant interplay between the cortical and

the thalamo-cortical brain structures. To study the dynamics of the interactions, time-variant partial directed coherence (PDC), a measure of effective connectivity, was used which allows analysis in the time-frequency range. The main results of the grand mean PDC analysis are: (1) PDC time-frequency patterns are frequently associated with phase-locked oscillations. (2) Interhemispheric interactions are dominant between frontal, central and occipital electrodes and intrahemispheric interactions Batimastat mouse are much less substantial. (3) An interaction breakdown for the frequency ranges 1-4 Hz (Fp(1) double right arrow Fp(2)) and 0.5-3 Hz (Fp(2) double right arrow Fp(1)) exists which lasts about 2.5 s and which is located at about burst onset. (4) Strong interactions in the high-frequency range 3.5-4.5 Hz between the frontal electrodes can be observed for both directions at the burst onset. It can be concluded that the evolution of strong interactions in the high-frequency range, which starts shortly before or at the burst onset from frontal regions to anteroposterior directions as well as the frontal interhemispheric interactions,

are associated with the burst onset generation. Additionally, the collapsing of the interactions before burst onset and after the burst are indicative of neuronal reorganisation processes. (C) 2010 Elsevier Ireland Ltd. All rights reserved.”
“We characterized heptaminol a human H5N1 virus isolate (KAN-1) encoding a hemagglutinin (HA) with a K-to-E substitution at amino acid position 222 that was previously described to be selected in the lung of the infected patient. In mice, the growth of the HA(222E)-encoding virus was mainly confined to the lung, but reversion to 222K allowed virus to spread to the brain. The HA(222E) variant showed an overall reduced binding affinity compared to that of HA(222K) for synthetic Neu5Ac2-3Gal-terminated receptor analogues, except for one analogue [Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)(6-HSO(3)) GlcNAc beta, Su-SLe(x)].

(C) 2009 Elsevier Ireland

(C) 2009 Elsevier Ireland Wortmannin nmr Ltd. All rights reserved.”
“Objective: We sought to determine

the effect of neoadjuvant chemoradiotherapy followed by surgical intervention on health-related quality of life in patients with esophageal cancer.

Methods: Health-related quality of life was evaluated in a prospective phase II study of neoadjuvant chemoradiotherapy followed by esophagectomy in 52 patients with carcinoma of the esophagus. Esophagectomy was performed 6 weeks after completion of induction. Functional Assessment of Cancer Therapy-Esophageal scoring was performed before treatment, 7 weeks after initiation of neoadjuvant therapy, before resection, and at 1, 3, and 6 months and 1 year after resection.

Results: Forty-three patients completed the entire treatment protocol. Functional Assessment of Cancer Therapy-Esophageal scores decreased significantly after chemoradiation at week 7 (120 vs 127 this website at baseline, P = .04) but returned to baseline levels before surgical intervention (127). Similarly, scores decreased significantly after surgical intervention (115 at 1 month, P = .02) but returned to baseline levels by 3 months postoperatively (127). At 1 year postoperatively, there was a statistically significant improvement in scores compared with those at baseline (139,

P = .003). Functional Assessment of Cancer Therapy- Esophageal scores continued to increase over time for patients who were alive at least 1 year after the operation with or without disease but were observed to significantly decrease in those who died within 1 year after the operation (P = .0001). An increase in quality of life was associated with a significantly lower risk Calpain of death (P = .04).

Conclusion: Neoadjuvant therapy has a significant effect on health-related quality of life, but this is transient, with recovery to baseline within 5 to 7 weeks after completion of induction therapy. Health-related quality of life decreases again after surgical intervention but returns to baseline levels

within 3 months.”
“Alzheimer’s disease (AD) is characterized by the pathological deposition of amyloid-P protein in the aged brain. Inefficient clearance of amyloid-beta from brain tissue is believed to play a major role in the pathogenesis of these deposits. Since amyloid-P clearance likely involves activation of microglial cells via toll-like receptors and since these receptors and their signaling pathways are regarded as potential therapeutic targets, we have studied the expression of toll-like receptor (tlr) mRNAs in an animal model of AD (APP23 transgenic mice). Laser microdissection was used to harvest plaques, tissue surrounding plaques and plaque-free tissue from cortex of aged APP23 transgenic mice and age-matched controls. Real-time RT-PCR was employed to quantify expression levels of different tlr mRNAs in these tissues. This revealed a strong upregulation of tlr2, tlr4.


“Introduction The impact of preformed donor-specific anti


“Introduction. The impact of preformed donor-specific antibodies (DSA) is incompletely understood in liver transplantation.

The incidence and impact of preformed DSA on early post liver transplant were assessed and these were correlated with compliment fragment C4d on allograft biopsy. Methods. Pretransplant serum from 41 consecutive liver transplant recipients (brain dead donors; DBD = 27 and cardiac death donors; DCD = 14) were tested for class-specific anti-human leukocyte antigen (HLA) and compared against donor HLA types. Liver biopsies were taken during cold storage (t-1) and post-reperfusion AZD3965 supplier (t0) stained with C4d and graded for preservation-reperfusion injury (PRI). Results. Of the 41 recipients, 8 (20%) had anti-HLA class I/II antibodies pretransplant, 3 (7%) were confirmed preformed DSA; classes I and II (n=1) and class I only (n=2). No biopsies showed definite evidence of antibody-mediated rejection. Graft biopsies in overall showed Cediranib nmr only mild PRI with ischemic hepatocyte C4d pattern similar in both positive and negative DSA patients. One DSA-positive (33%) compared with four DSA-negative patients (10%) had significant early graft

dysfunction; severe PRI causing graft loss from primary nonfunction was seen only in DSA-negative group. Allograft biopsy of preformed DSA-positive patient demonstrated only minimal PRI; however, no identifiable cause could be attributed to graft dysfunction other than preformed DSA. Conclusion. Preformed DSA are present in 5-10% liver transplant recipients. There is no association between anti-HLA DSA and PRI and C4d, but preformed DSA may cause early morbidity. Larger studies on the impact of DSA with optimization of C4d techniques are required.”
“Background and aims. Determination of hepatic copper (Cu) concentration is important in Wilson’s disease (WD) diagnosis. The aim of this study was to evaluate

uneven distribution of liver Cu concentration and the utility of double-sample biopsy dipyridamole in WD diagnosis. Methods. Thirty-five WD patients (20 male; mean age 41 +/- 9 years) were enrolled in the study and double-liver samples for biopsy were obtained. A further 30 WD patients, in whom Cu determination was performed using single-liver samples, were also enrolled as controls. Results. A marked difference in hepatic Cu concentration was observed between the two sample groups (p < 0.0001). This difference is statistically significant for all levels of liver fibrosis (p < 0.001) and for the comparison of hepatic and neurological phenotypes (p < 0.01). The sensitivity of the Cu concentrations obtained from the double-sample biopsies for the conventional cut-off value of 250 mg/g dry weight of tissue was 85.7% compared to 80% in the single-sample biopsies.