Interpersonal sensitivity and persistent attenuated psychotic symptoms in adolescence.

Interpersonal sensitivity defines feelings of inner-fragility in the presence of others due to the expectation of criticism or rejection. Interpersonal sensitivity was found to be related to attenuated positive psychotic symptom during the prodromal phase of psychosis. The aims of this study were to examine if high level of interpersonal sensitivity at baseline are associated with the persistence of attenuated positive psychotic symptoms and general psychopathology at 18-month follow-up. A sample of 85 help-seeking individuals (mean age = 16.6, SD = 5.05) referred an Italian early detection project, completed the interpersonal sensitivity measure and the structured interview for prodromal symptoms (SIPS) at baseline and were assessed at 18-month follow-up using the SIPS. Results showed that individuals with high level of interpersonal sensitivity at baseline reported high level of attenuated positive psychotic symptoms (i.e., unusual thought content) and general symptoms (i.e., depression, irritability and low tolerance to daily stress) at follow-up. This study suggests that being "hypersensitive" to interpersonal interactions is a psychological feature associated with attenuated positive psychotic symptoms and general symptoms, such as depression and irritability, at 18-month follow-up. Assessing and treating inner-self fragilities may be an important step of early detection program to avoid the persistence of subtle but very distressing long-terms symptoms.

A low-cost and versatile system for projecting wide-field visual stimuli within fMRI scanners.

We have constructed and tested a custom-made magnetic-imaging-compatible visual projection system designed to project on a very wide visual field (~80°). A standard projector was modified with a coupling lens, projecting images into the termination of an image fiber. The other termination of the fiber was placed in the 3-T scanner room with a projection lens, which projected the images relayed by the fiber onto a screen over the head coil, viewed by a participant wearing magnifying goggles. To validate the system, wide-field stimuli were presented in order to identify retinotopic visual areas. The results showed that this low-cost and versatile optical system may be a valuable tool to map visual areas in the brain that process peripheral receptive fields.

Brain connectivity is altered by extreme physical exercise during non-REM sleep and wakefulness: indications from EEG and fMRI studies.

Brain connectivity is associated to behavioral states (e.g. wake, sleep) and modified by physical activity although, to date, it is not clear which components (e.g. hypothalamus-pituitary-adrenal axis hormones, cytokines) associated to the exercise are involved. In this pilot study, we used extreme exercise (UltraTriathlon) as a model to investigate physical-activity-related changes of brain connectivity. We studied post-race brain synchronization during wakefulness and sleep as well as possible correlations between exercise-related cytokines/hormones and synchronization features. For wakefulness, global synchronization was evaluated by estimating from fMRI data (12 athletes) the brain global connectivity (GC). GC increased in several brain regions, mainly related to sensory-motor activity, emotional modulation and response to stress that may foster rapid exchange of information across regions, and reflect post-race internally-focused mental activity or disengagement from previous motor programs. No significant correlations between cytokines/hormones and GC were found. For sleep (8 athletes), synchronization was evaluated by estimating the local-(cortical) and global-related (thalamo- cortical) EEG features associated to the phenomenon of Sleep Slow Oscillations (SSO) of NREM sleep. Results showed that: power of fast rhythms in the baseline preceding the SSO increased in midline and parietal regions; amplitude and duration of SSOs increased, mainly in posterior areas; sigma modulation in the SSO up state decreased. In the post race, IL-10 positively correlated with fast rhythms baseline, SSO rate and positive slope; IL-1ra and cortisol inversely correlated with SSO duration; TNF-α and C-reactive protein positively correlated with fast rhythm modulation in the SSO up state. Sleep results suggest that: arousal during sleep, estimated by baseline fast rhythms, is increased; SSO may be sustained by cortical excitability, linked to anti-inflammatory markers (IL-10); thalamo-cortical entrainment, (sigma modulation), is impaired in athletes with higher inflammatory markers.

BOLD human responses to chromatic spatial features.

Animal physiological and human psychophysical studies suggest that an early step in visual processing involves the detection and identification of features such as lines and edges, by neural mechanisms with even- and odd-symmetric receptive fields. Functional imaging studies also demonstrate mechanisms with even- and odd-receptive fields in early visual areas, in response to luminance-modulated stimuli. In this study we measured fMRI BOLD responses to 2-D stimuli composed of only even or only odd symmetric features, and to an amplitude-matched random noise control, modulated in red-green equiluminant colour contrast. All these stimuli had identical power but different phase spectra, either highly congruent (even or odd symmetry stimuli) or random (noise). At equiluminance, V1 BOLD activity showed no preference between congruent- and random-phase stimuli, as well as no preference between even and odd symmetric stimuli. Areas higher in the visual hierarchy, both along the dorsal pathway (caudal part of the intraparietal sulcus, dorsal LO and V3A) and the ventral pathway (V4), responded preferentially to odd symmetry over even symmetry stimuli, and to congruent over random phase stimuli. Interestingly, V1 showed an equal increase in BOLD activity at each alternation between stimuli of different symmetry, suggesting the existence of specialised mechanisms for the detection of edges and lines such as even- and odd-chromatic receptive fields. Overall the results indicate a high selectivity of colour-selective neurons to spatial phase along both the dorsal and the ventral pathways in humans.

Physical training effects in renal transplant recipients.

INTRODUCTION: Several studies demonstrated the benefits of rehabilitation in uraemic patients. This study evaluates physical and psychosocial effects of exercise on renal transplant recipients (RTRs). PATIENTS AND METHODS: Eight RTRs were evaluated before and after an exercise training consisting of thirty 40-minute sessions, three times a week, performed with the interval training technique. RESULTS: Hospital Anxiety and Depression Scale (HADS) significantly decreased (p<0.04 and <0.008, respectively). Quality of life mean scores (SF-36 test) significantly increased (p<0.000). No differences were recorded for muscle and fat mass, maximal explosive power of the lower limbs, alkaline and acid phosphatase, parathormone (PTH), myoglobin, lipoprotein-A, glomerular filtration rate (GFR), at rest heart rate, and cardiac troponin. IL-6 decreased from 2.8±0.6 to 1.7±0.5 pg/mL (p<0.01). Resting MAP fell from 112±4 to 99±3 mmHg (p<0.02). The metabolic threshold rose from 33±4 to 43±5% (p<0.033). The blood lactate level at peak exercise increased from 5.2±0.9 to 6.2±0.7 mmol/L (p<0.012). The maximum oxygen uptake increased from 1200±210 to 1359±202 mL/min (p<0.05), iso-load oxygen uptake decreased from 1110±190 to 1007±187 mL/min (p<0.034). The maximum working capacity increased from 90±14 to 115±15 watts (p<0.000). CONCLUSION: This study suggests that an appropriate dose of physical training is a useful, safe and non-pharmacologic contribution to RTR treatment.

Diffusion tensor MRI and MR spectroscopy in long lasting upper motor neuron involvement in amyotrophic lateral sclerosis.

Upper motor neuron (UMN) dysfunction in Amyotrophic Lateral Sclerosis (ALS) is not easy to identify clinically: Diffusion Tensor Imaging (DTI) and single-voxel Magnetic Resonance Spectroscopy (H-MRS) can identify markers of UMN involvement. The aim of this study was to correlate brain DTI and MRS data with clinical parameters in ALS patients (PALS). We studied 32 PALS using Magnetic Resonance Imaging. The subjects were subdivided into definite/probable (D/P) and possible/suspected (P/S). DTI indices included Fractional Anisotropy (FA) and averaged Apparent Diffusion Coefficient (avADC). Anatomical areas were sampled by positioning regions of interest along corticospinal tracts, from the precentral cortex to the bulb. H-MRS voxels were localized bilaterally in precentral regions. D/P-PALS showed significantly lower FA values than healthy controls in almost all regions, whereas P/S-PALS FA values were significantly lower only in the left precentral gray matter (GM), right precentral white matter (WM), cerebral peduncles (CP), left hemipons, and left bulbar pyramid (BP). Significantly higher avADC values were observed in the D/P-PALS right precentral GM, precentral WM, right semioval center-posterior limb of the internal capsule (SC-PLIC), and left CP; and in the precentral WM, right SC-PLIC, left CP, and right hemipons of P/S-PALS. With increasing disability, only D/P-PALS showed significantly reduced FA values in the left precentral WM and hemipons, and increased avADC values in the precentral WM. Significantly lower N-acetylaspartate (NAA)/creatine-phosphocreatine complex (Cr) and higher choline (Cho)/Cr and myoinositol (mI)/Cr ratios were found in D/P-PALS, while only higher Cho/Cr and mI/Cr ratios were found in P/S-PALS. Our data highlight the usefulness of DTI and H-MRS in assessing UMN involvement. Given FA sensitivity and specificity, despite the small number of PALS, our findings support its use as a diagnostic marker in D/P-PALS.

Plasticity of the human visual brain after an early cortical lesion.

In adults, partial damage to V1 or optic radiations abolishes perception in the corresponding part of the visual field, causing a scotoma. However, it is widely accepted that the developing cortex has superior capacities to reorganize following an early lesion to endorse adaptive plasticity. Here we report a single patient case (G.S.) with near normal central field vision despite a massive unilateral lesion to the optic radiations acquired early in life. The patient underwent surgical removal of a right hemisphere parieto-temporal-occipital atypical choroid plexus papilloma of the right lateral ventricle at four months of age, which presumably altered the visual pathways during in utero development. Both the tumor and surgery severely compromised the optic radiations. Residual vision of G.S. was tested psychophysically when the patient was 7 years old. We found a close-to-normal visual acuity and contrast sensitivity within the central 25° and a great impairment in form and contrast vision in the far periphery (40-50°) of the left visual hemifield. BOLD response to full field luminance flicker was recorded from the primary visual cortex (V1) and in a region in the residual temporal-occipital region, presumably corresponding to the middle temporal complex (MT+), of the lesioned (right) hemisphere. A population receptive field analysis of the BOLD responses to contrast modulated stimuli revealed a retinotopic organization just for the MT+ region but not for the calcarine regions. Interestingly, consistent islands of ipsilateral activity were found in MT+ and in the parieto-occipital sulcus (POS) of the intact hemisphere. Probabilistic tractography revealed that optic radiations between LGN and V1 were very sparse in the lesioned hemisphere consistently with the post-surgery cerebral resection, while normal in the intact hemisphere. On the other hand, strong structural connections between MT+ and LGN were found in the lesioned hemisphere, while the equivalent tract in the spared hemisphere showed minimal structural connectivity. These results suggest that during development of the pathological brain, abnormal thalamic projections can lead to functional cortical changes, which may mediate functional recovery of vision.

Tacrolimus Therapeutic Drug Monitoring in Stable Kidney Transplantation and Individuation of CYP3A5 Genotype.

The posology of tacrolimus (TAC) is usually guided by its therapeutic drug monitoring. Some patients reach target concentrations (CTs) quickly, others more slowly. In a retrospective study, 20 kidney transplant recipients were included (mean age, 50.7 ± 14.1 years; weight 64.0 ± 14.2 kg; patients clinically stable for over a year). We studied cytochrome CYP3A5 genotype, in particular CYP3A5 6986A>G, the most important polymorphism related to the metabolism of TAC (wild genotype CYP3A5 *1 genotype, and CYP3A5 *3 variants). One year after transplantation, the CTs were 5.0 to 8.0 ng/mL. The patients were divided into group A (TAC doses < 6.0 mg/d) and group B (TAC doses > 6.0 mg/d). All were tested for the CYP3A5 gene sequence to characterize their polymorphism. Patients with CYP3A5 *1/*1 and *1/*3 were extensive metabolizers, and those with CYP3A5 *3/*3 were poor metabolizers. In group A and group B, the average TAC doses at the time of therapeutic drug monitoring were 3.0 ± 1.4 ng/mL (0.05 ± 0.03 mg/kg) and 12.8 ± 3.7 ng/mL (0.2 ± 0.1 mg/kg), respectively (P < .001). Group A was the poor metabolizers genotype, while in group B, the extensive metabolizers genotype was present. Patients with the CYP3A5 *1/*1 or *1/*3 genotype required 1.5 to 2 times higher doses than patients *3/*3 to reach CT. This genetic test allows clinicians to know, before the kidney transplant, the patient's TAC metabolism pattern and then to optimize the drug exposure.

A cortical area that responds specifically to optic flow, revealed by fMRI.

The continuously changing optic flow on the retina provides information about direction of heading and about the three-dimensional structure of the environment. Here we use functional magnetic resonance imaging (fMRI) to demonstrate that an area in human cortex responds selectively to components of optic flow, such as circular and radial motion. This area is within the region commonly referrred to as V5/MT complex, but is distinct from the part of this region that responds to translation. The functional properties of these two areas of the V5/MT complex are also different; the response to optic flow was obtained only with changing flow stimuli, whereas response to translation occurred during exposure to continuous motion.

Brain representation of phonological processing in Italian: individual variability and behavioural correlates.

Neuroimaging literature on phonological processing during reading lacks of studies taking into account orthographic differences across languages and behavioural variability across subjects. The present study aimed at investigating brain representation of phonological processing in reading Italian, a language with regular orthography, with particular regard to inter-individual variability and brain-behavioural correlates. Ten Italian adults performed a rhyme generation and a rhyme judgment task during fMRI acquisition and were tested with behavioural measures of phonological processing. Results for both tasks showed activations of the left Inferior Frontal Gyrus and Dorsolateral Prefrontal Cortex, likely underlying output sublexical strategies, for all or most of the subjects, while a minority of subjects activated the Superior Temporal Sulcus and the Temporo-Parietal-Occipital Junction. These results suggest that phonological processing of written Italian is based on the prevalent use of frontal structures. However, it is of interest that the activation of the Superior Temporal Sulcus, involved in phonological input, was associated to better behavioural performances in tasks of phonological processing. Our findings may contribute to understand neural correlates of phonological processing of languages with regular orthography.

Reorganisation of the somatosensory system after early brain damage.

OBJECTIVE: To examine the reorganisation of the somatosensory system after early brain lesions. METHODS: We studied 12 young patients with congenital hemiplegia. Causative lesions were brain malformations, periventricular injuries and cortico-subcortical lesions. We explored the somatosensory system using evoked potentials, fMRI during sensory stimulation and clinical assessment of sensory function. To correlate sensory and motor function, we also performed transcranial magnetic stimulation, fMRI of hand movement and assessment of motor function by means of Melbourne test. RESULTS: Eleven patients showed a perilesional reorganisation of primary somatosensory function, as expressed by short latency potentials following stimulation of the paretic hand; in a remaining patient, delayed latency responses (N27.1) were only elicited over the ipsilateral undamaged hemisphere. Five of the eleven patients with perilesional somatosensory representation of the affected hand showed contralesional shifting of motor function, thus exhibiting sensory-motor dissociation. Significant correlation was found between sensory deficit and fMRI activation during sensory stimulation. CONCLUSIONS: In subjects with early brain lesions, somato-sensory function is generally reorganised within the affected hemisphere. A contralesional shifting is uncommon and poorly efficient in function restoration. SIGNIFICANCE: This study confirms and further explores the difference in reorganisation capabilities of the motor and sensory system following early brain injury of different etiologies and timing.

The pathogenesis of the white matter abnormalities in phenylketonuria. A multimodal 3.0 tesla MRI and magnetic resonance spectroscopy (1H MRS) study.

OBJECTIVE: To gain insights into the nature and pathogenesis of white matter (WM) abnormalities in PKU. METHODS: Thirty-two patients with phenylalanine hydroxylase deficiency (21 with early and 11 with late diagnosis and treatment) and 30 healthy controls underwent an integrated clinical, neuroimaging (3.0 T MRI, diffusion-weighted imaging (DWI), diffusion tensor imaging (DTI)) and neurochemical (1H MRS) investigation. RESULTS: All patients had white matter abnormalities on T2-weighted (T2W) and fluid-attenuated inversion recovery (FLAIR) scans; parietal white was consistently affected, followed by occipital, frontal and temporal white matter. T1-weighted hypointense alterations were also found in 8 of 32 patients. DWI hyperintense areas overlapped with those detected on T2W/FLAIR. The apparent diffusion coefficient (ADC) was reduced and correlated inversely with severity of white matter involvement. Fractional anisotropy index, eigenvalues lambda(min), lambda(middle), lambda(max) obtained from DTI data, and the principal brain metabolites assessed by 1H MRS (except brain phenylalanine (Phe)) were normal. Brain Phe peak was detected in all but two subjects. Brain and blood Phe were strictly associated. Blood Phe at the diagnosis, patient's age, and concurrent brain Phe independently influence white matter alteration (as expressed by conventional MRI or ADC values). CONCLUSIONS: (a) MRI abnormalities in phenylketonuria are the result of a distinctive alteration of white matter suggesting the intracellular accumulation of a hydrophilic metabolite, which leaves unaffected white matter architecture and structure. (b) White matter abnormalities do not seem to reflect the mechanisms involved in the derangement of mental development in PKU. (c) Our data do not support the usefulness of conventional brain MRI examination in the clinical monitoring of phenylketonuria patients.

Intraperitoneal Tenckhoff catheter for the treatment of recurrent lymphoceles after kidney transplantation: our early experience.

Lymphoceles may occur as frequently as 16% of the time after kidney transplantation, becoming clinically evident between 18 and 180 days after surgery. The management of lymphoceles is unclear. Percutaneous needle aspiration and external drainage are associated with high recurrence and complications. Surgical intraperitoneal marsupialization of lymphocele is considered the treatment of choice, but requires hospital admission, general anesthesia, and sometimes extensive surgical dissection. We discuss our experience in the treatment of recurrent symptomatic lymphocele intraperitoneally drained using a Tenckhoff catheter in 7 consecutive patients. Clinical manifestations became evident between 26 and 90 days after transplantation. The diagnosis was obtained with abdominal ultrasound in all cases; mean lymphocele diameter was 14 +/- 6 cm. After percutaneous drainage, performed to differentiate urinoma/lymphocele and to rule out infections, the lymphocele recurred within 1 month. Thereafter, we decided to treat recurrent lymphatic collection using a Tenckhoff catheter. The lymphocele was located during the operative procedure using a sterile 3.5-MHz ultrasound probe. With the patient under local anesthesia, we performed 2 vertical 1-cm incisions to the lymphocele and peritoneum, respectively. The Tenckoff catheter was first positioned into the lymphocele and the tunneled inside the peritoneal cavity. One cuff of the Tenckhoff was fixed to the fascia to avoid possible delocalization. The patients were discharged the same day. The catheter was removed 6 months later with no evidence of lymphocele recurrence.

[Uretero-vescical anastomosis during kidney transplantation. Preliminary results of two surgical techniques]. / L'anastomosi uretero-vescicale nel trapianto di rene. Risultati preliminari di due tecniche a confronto.

AIM: The most frequent urologic complications after renal transplantation involve the uretero-vescical anastomosis (leakage, stenosis, and reflux), with a frequency of 1% to 30% in different series. METHODS: We present our results in a prospective randomized trial performed from October 2004 to September 2005, in a cohort of 36 patients, who underwent renal transplantation from cadaveric donor at our institution. A uretero-vescical anastomosis according to Lich-Gregoir was used in 18 cases (group A), whereas an anastomosis according to Knechtle was performed in other 18 patients (group B), respectively. The groups were comparable for donors and recipients characteristics. The mean donor age was 46.3 years vs 44.9 years, and the mean duration of cold ischemia was 1 086+/-296 min vs 1 100+/-381 min for group A and for group B respectively. The mean recipient age was 47.5 years vs 46.1 for group A and group B, respectively. RESULTS: No differences were evidenced between the two uretero-vescical anastomosis in term of surgical complications, infections or patient and graft survival at one year of follow-up. Stenosis and leakage involved 2 patients for each group respectively. Numbers of infections, days of antibiotic therapy were similar between the two groups. CONCLUSION: Our early experience does not evidence differences between the two types of uretero-vescical anastomosis.

[Anemia after renal transplantation]. / L'anemia nel trapiantato di rene.

The anemia which commonly accompanies end-stage kidney disease usually remits within 10 - 16 weeks following successful kidney transplantation. However, a significant number of patients remain anemic or become anemic after transplantation. Unlike the great amount of data available on anemia in end-stage renal disease population, much less is known about post-transplant anemia (PTA). Existing literature data indicate that PTA prevalence is high; the findings of a few longitudinal studies showed a very high prevalence of PTA in the early post-transplantation period; during the first 5-year post-transplant period, 30-40% of transplant patients are anemic, and PTA increases subsequently after transplantation. Available information suggests that PTA prevalence is higher in pediatric compared to adult patients. A decrease in renal allograft function has been identified in several studies as the most important risk factor for PTA development. Other common causes of PTA include iron deficiency, systemic illnesses, acute and chronic infections, and drug toxicities. Several reports indicate that PTA is associated with an increased cardiovascular disease risk. Although PTA is a frequent problem in transplanted patients, iron and erythropoietin therapy are even underused in this population. Erythropoietinis effective and safe in correcting anemia during both early and late post-transplantation period. Prospective interventional studies in anemic kidney transplant recipients are needed to determine the most appropriate hemoglobin target in these patients and the potential beneficial role of erythropoietin therapy for cardiovascular and renal protection.

De novo malignancies after kidney and liver transplantations: experience on 582 consecutive cases.

De novo malignancies after transplantation are a growing problem of solid organ transplant recipients, due to longer survival follow-up under chronic immunosuppression. The aim of this study was to analyze a population of 582 consecutive kidney (n = 382) and liver (n = 202) transplant recipients, who survived at least 12 months after transplantation, at a single transplant center for the development of de novo cancers. The incidence of de novo malignancies was 7% after both renal and liver transplantation. The median elapsed time from transplant to the diagnosis of de novo malignancy was 45 months (range 3 to 220) months for kidney and 37 months (range 12 to 101 months) for liver transplants. Skin cancers were the most common within renal recipients, while gastroenteric cancers were more frequently encountered in liver transplants. Oropharyngeal and upper digestive tract tumors were always associated with a history of chronic alcohol consumption in liver recipients. Liver transplant recipients treated for acute rejection had a worse cancer prognosis than patients without rejection 1- and 2-year survivals 83% and 63% versus 36% and 17% (P = .026). The estimated 1- and 2-year survival rates for all types of de novo malignancies were 79% and 66%, including 64% and 51% for solid organ tumors versus 89% and 89% for skin cancers and posttransplant lymphoproliferative disorder (PTLD) (P = .17) in renal transplants and 70% and 42%, including 57% and 28% for solid organ tumors versus 85% and 64% for skin cancers and PTLD (P = .43) in liver transplants respectively.

CD55 is a HIF-2α marker with anti-adhesive and pro-invading properties in neuroblastoma.

CD55 has been revealed to have an important role in tumor genesis, and presence of small populations of cells with strong CD55 expression would be sufficient to predict poor prognosis of several tumors. In our study we revealed that CD55 is a novel target of hypoxia-inducible factor HIF-2α in neuroblastoma (NB) cells. We show that HIF-2α expression is sufficient to sustain stem-like features of NB cells, whereas CD55 protein upon HIF-2α expression contributes to growth of colonies and to invasion of cells, but not to stemness features. Interestingly, in NB tissues, CD55 expression is limited to quite a small population of cells that are HIF-2α positive, and the gene expression of CD55 in the NB data set reveals that the presence of CD55(high) affects prognosis of NB patients. The functional characterization of CD55-positive populations within heterogeneous NB monoclonal cell lines shows that CD55 has pro-invading and anti-adhesive properties that might provide the basis for the ability of solid tumors to survive as microscopic residual disease. The easy accessibility to CD55 membrane antigen will offer the possibility of a novel antibody approach in the treatment of recurrent tumors and will provide a ready target for antibody-based visualization in NB diagnosis and prognosis.

Antiestrogens upregulate estrogen receptor beta expression and inhibit adrenocortical H295R cell proliferation.

The molecular mechanisms involved in adrenocortical tumorigenesis are still not completely understood. In this study, using the H295R cell line as a model system, we investigated the role of estrogens and estrogen receptor (ER) alpha and ER beta in the growth regulation of adrenocortical tumors. We demonstrated that H295R cells are able to convert androgens to estrogens by a constitutive expression of active cytochrome P450 aromatase protein and express ER beta to a greater extent than ER alpha. Moreover, physiological concentrations of 17beta-estradiol (E2) determined an increase of thymidine incorporation, suggesting the presence of an autocrine mechanism in maintaining H295R cell proliferation. Evaluating the response to ER antagonists like 4-hydroxytamoxifen (OHT) and ICI 182 780 (ICI), we observed an up-regulation of ER beta and a dose-dependent inhibition of H295R cell proliferation. Whereas ICI determined the growth arrest of H295R cells, OHT induced morphological changes that were characteristic of apoptosis. According to the above-mentioned observations, OHT but not ICI clearly induced a marked expression of FasL and the cleavage of both caspase-8 and caspase-3. Interestingly, the apoptotic effects of OHT in H295R cells may be consequent to the enhanced levels of ER beta which stimulate the expression of FasL interacting with activating protein (AP)-1 sites located within its promoter sequence. In conclusion, we have demonstrated that H295R cells are able to transform androgens to estrogens that activate an autocrine mechanism, mediated by their own receptors, and contribute to regulate the proliferation of these cells. Moreover, this study points towards a role for ER beta as an important mediator of the repressive effects exerted by antiestrogens on H295R cells; however, further studies are needed to clarify its role in the control of adrenocortical cell proliferation and on the potential benefits of antiestrogens for treatment of adrenocortical cancer.

Cryopreserved human hepatocytes from cell bank: in vitro function and clinical application.

UNLABELLED: We Aimed to analyze the in vitro function of isolated and cryopreserved human hepatocytes (CHH) from a cell bank and to define their potential clinical application in a bioartificial liver (BAL) device. METHODS: Over 24 months, 103 not transplantable livers were utilized for human hepatocytes isolation and cryopreservation. Hepatocytes isolated by collagenase were analyzed for yield, viability, diazepam metabolism, and production of human albumin after isolation and cryopreservation in LN(2). RESULTS: The causes for refusal for transplantation were macrosteatosis >60%, ischemic damage due to donor hypotension, and nonviral cirrhosis in 60%, 11%, and 8%, respectively. Cell yields averaged 7 million hepatocytes per gram of liver of mean viability of 80% +/- 13%. The viability of CHH after thawing averaged 50%. Thawed hepatocytes showed diazepam metabolism, and human albumin synthesis comparable to fresh cells. CHH were utilized as the biological component of a BAL for temporary support as three applications of two patients affected by fulminant hepatic failure awaiting urgent transplant. Ten to 13 billion viable CHH were loaded into each BAL. Liver function showed bilirubin and ammonia reduction at the end of each treatment. One patient was successfully bridged to emergency OLTx after one BAL; in the second case there was spontaneous recovery of liver function after two BAL. CONCLUSIONS: Recovery of donor human livers unwanted for transplantation allowed isolation and cryopreservation of viable and functionally active human hepatocytes, which have been banked and successfully used for clinical applications of a BAL device.