Microalgae production in olive mill wastewater fractions and cattle digestate slurry: Bioremediation effects and suitability for energy and feed uses.

The possibility of obtaining energy or nutritive streams and bioremediation as an add-on opens new perspectives for the massive culturing of microalgal biomass on waste waters generated by the agro-food sector. Ordinary revenue streams are fully preserved, or even boosted, if they are used in microalgal cultivation; however, the suitability of wastewaters depends on multiple nutritional and toxic factors. Here, the effect of modulating the Olive Mill Wastewater (OMW) and cattle digestate (CD) fraction in the formulation of a growth medium on biomass accumulation and productivity of selected biomass fractions and their relevance for biofuel and/or feed production were tested for the microalga Scenedesmus dimorphus and for the cyanobacterium Arthrospira platensis (Spirulina). Tests highlighted the strong S. dimorphus adaptability to digestate, as on OMW, compared to A. platensis, with the maximum lipid storage (48 %) when culture medium was composed by 50 % of cattle digestate.

Coupling anaerobic co-digestion of winery waste and waste activated sludge with a microalgae process: Optimization of a semi-continuous system.

Wine production represents one of the most important agro-industrial sectors in Italy. Wine lees are the most significant waste in the winery industry and have high disposal and storage costs and few applications within the circular economy. In this study, anaerobic digestion and a microalgae coupled process was studied in order to treat wine lees and waste activated sludge produced within the same facility, with the aim of producing energy and valuable microalgae biomass that could be processed to recover biofuel or biostimulant. Chlorella vulgaris was cultivated on liquid digestate in a semi-continuous system without biomass recirculation. The best growth and phytoremediation performance were achieved applying a hydraulic retention time (HRT) of 20 days with a stable dry weight, lipid and protein storage of 1.85 ± 0.02 g l-1, 33.48 ± 7.54 % and 57.85 ± 10.14 % respectively. Lipid characterization highlighted the potential use in high quality biodiesel production, according to EN14214 (<12 % v/v linolenic acid). The microalgae reactor's liquid output showed high removal of ammonia (95.72 ± 2.10 %), but low organic soluble matter reduction. Further semi-continuous process optimization was carried out by increasing the time between digestate feeding and biomass recovery at HRT 10. These operative changes avoided biomass wash-out and provided a stable phytoremediation of the digestate with 84.58 ± 4.02 % ammonia removal, 33.01 ± 1.44 % sCOD removal, 38.06 ± 2.65 % of polyphenols removal.

Evaluation of Chlorella vulgaris and Scenedesmus obliquus growth on pretreated organic solid waste digestate.

In this research Scenedesmus obliquus and Chlorella vulgaris growth was tested on digestate sludge obtained from the anaerobic co-digestion treatment of the organic fraction of municipal solid waste (OFMSW) together with waste activated sludge (WAS). Digestate was diluted 1:10 and tested in three batch experimental conditions: with no pre-treatments (noPT), after centrifugation (AC) and after filtration (AUF), in order to evaluate microalgae limiting growth factors. The best growth was obtained by C. vulgaris on digestate AC compared to S. obliquus, reaching 479 ± 31 cell million ml-1 and 131 ± 12 cell million ml-1 respectively. Ammonia removal evaluated in C. vulgaris and S. obliquus cultures was 99.2% ± 0.3 and 98.146% ± 0.008 in AC condition, respectively. Considering that AUF showed similar microalgae growth values, the digestate pretreatment for microalgae growth, could be limited to centrifugation.

Deformed wing virus type a and b in managed honeybee colonies of Argentina.

Apis mellifera is infected by more than 24 virus species worldwide, mainly positive-sense, single-stranded RNA viruses of the Dicistroviridae and Iflaviridae families. Among the viruses that infect honey bees, Deformed wing virus is the most prevalent and is present as three master variants DWV-A, B, and C. Given that the ectoparasitic mite Varroa destructor vectors these virus variants, recombination events between them are expected, and variants and their recombinants can co-exist in mites and honeybees at the same time. In this study, we detect, through RT-qPCR, the presence of DWV-A and B in the same samples of adult bees from colonies of Argentina. Total RNA was extracted from pools of ten adult bees from 45 apiaries distributed across the main beekeeping Provinces of Argentina (Buenos Aires, Santa Fe, Córdoba, Santiago del Estero, Río Negro, and Mendoza); then RT-qPCR reactions were performed to detect DWV-A and B, with specific primer pairs. After the amplifications, PCR products (204 and 660 bp amplicons for DWV-B, and ~250 bp for DWV-A) were purified and sequenced to verify that they corresponded to reported sequences, analyzing them using the Blast software. Of the 45 samples analyzed by RT-qPCR, over 90% were infected with DWV-A and 47% were also positive for DWV-B, where it was found in high prevalence specifically in colonies of A. mellifera of the Buenos Aires Province. Future studies will determine the impact of this type of the virus and its ability to recombine with the other DWV types in the apiaries of our country.

The effectiveness of extracorporeal shock wave therapy on breast cancer-related lymphedema: A literature review.

Lymphedema is one of the most dreaded complications related to breast cancer surgery, commonly resulting in upper limb functional, esthetic, and psychological impairment. The necessity to improve the efficacy of conventional treatments and the promising effect of extracorporeal shock wave therapy (ESWT) on lymphangiogenesis in vitro and animal models, has prompted studies involving women affected by breast cancer-related lymphedema. Since intervention modalities and treatment protocols used are different, a review is necessary to verify the effectiveness of ESWT, evaluating the quality of existing studies and the eventual need for further research. Data were obtained from PubMed, Scopus, Google Scholar, Cochrane Library and PEDro, including articles published until January 2019. Five studies met the inclusion criteria. Evident heterogeneity emerged among selected studies permitting only a purely descriptive analysis of their data and strongly limiting their comparison. When compared to other treatment modalities, ESWT showed a significant effect on measured outcomes. It is clear that further high quality research is necessary to assert with confidence the effects and possible superiority of ESWT over other conservative therapies in the management of breast cancer-related lymphedema.

Hand motion analysis during robot-aided rehabilitation in chronic stroke.

A high percentage of post-stroke patients reports spasticity and no functional use of the upper limb. To adapt the therapy in the most patient-specific manner, it is of paramount importance to objectively assess motor improvement during rehabilitation therapy. In this paper, a quantitative evaluation of the results obtained by using a commercial exoskeletal glove for hand rehabilitation (i.e. Gloreha Sinfonia®) is performed. A camera-based calibration procedure for the bending sensors embedded in the Gloreha Sinfonia robotic glove for hand rehabilitation is introduced to retrieve the range of motion (i.e. the flexion angle excursion of the finger metacarpophalangeal joints) of the patients' hand. Once calibrated, the sensors embedded in the glove have been used to objectively assess the motor performance of chronic post-stroke patients that underwent a robotic treatment with the Gloreha Sinfonia glove. The preliminary results obtained on ten post-stroke patients demonstrated i) that the camera-based procedure permits to retrieve joints' angular values from bending sensors embedded in the glove ii) an improvement in motor performance.

Robotic treatment of the upper limb in chronic stroke and cerebral neuroplasticity: a systematic review.

Stroke is the second cause of mortality and the third cause of long-term disability worldwide. Deficits in upper limb (UL) capacity persist at 6 months post-stroke in 30-66% of hemiplegic stroke patients with major limitations in activity of daily living (ADL), thus making the recovery of paretic UL function the main rehabilitation goal. Robotic rehabilitation plays a crucial role since it allows to perform a repetitive, intensive, and task-oriented treatment, adaptable to the patients' residual abilities, necessary to facilitate recovery and the rehabilitation of the paretic UL. It has been proposed that robot-mediated training may amplify neuroplasticity by providing a major interaction of proprioceptive and/or other sensory inputs with motor outputs, with significant modifications in functional connectivity (coherence) within the fronto-parietal networks (inter- and intra-hemispheric functional connectivity) related to processes of movement preparation and execution. However, the neurophysiological mechanisms underlying this reorganization are not entirely clear yet. Therefore, the aim of this study is to revise the literature, which assesses the effect of robotic treatment in the recovery of UL deficits measured in terms of neuroplasticity in patients affected by chronic stroke. This systematic review was conducted using PubMed, PEDro, Cinahl (EBSCOhost), Scopus and Cochrane databases. The research was carried out until February 2020 it included articles written in English language, published between 2009 and 2020, and the outcomes considered were neuroplasticity assessments. We included 23 studies over 6145 records identified from the preliminary research. The selected studies proposed different methods for neuroplasticity assessment (i.e. transcranial direct current stimulation (tDCS), EEG-Based Brain Computer Interface (BCI) and Neuroimaging (fMRI)), and different Robotic Rehabilitation treatments. These studies demonstrated a positive correlation between changes in central nervous circuits and post-treatment clinical outcomes. Our study has highlighted the effectiveness of robotic therapy in promoting mechanisms that facilitate re-learning and motor recovery in patients with post-stroke chronic disabilities. However, future studies should overcome the limitations of heterogeneity found in the current literature, by proposing a greater number of high-level RCTs, to better understand the mechanisms of robot-induced neuroplasticity, follow the clinical progress, estimate a prognosis of recovery of motor function, and plan a personalized rehabilitative programme for the patients.

Robotic hand treatment of patients affected by chronic stroke: a monocentric longitudinal pilot study.

Few studies investigated the effects of a robotic treatment in hand motor recovery after stroke. Aim of the present study was to evaluate the efficacy of treatment by means of Gloreha Sinfonia® robotic glove in hand motor recovery of a chronic stroke sample of patients with different impairment severity. Thirteen chronic stroke subjects were assigned to either active-assisted robotic treatment or passive robotic treatment according to their ability to actively extend wrist for at least 20 degrees. All subjects underwent 20 sessions of treatment with Gloreha Sinfonia® and were evaluated before (T0), after treatment (T1) and after one month (T2) with clinical scales testing motor performance [Motor Power (MP); Fugl Meyer Upper-Extremity (FMUE)] and spasticity [Modified Ashworth Scale (MAS)]. Both groups showed significant motor recovery and spasticity reduction. Further randomized controlled trials with larger samples are needed to confirm our results.

Use of wearable systems for the detection of chest-abdominal wall movement aimed at respiratory monitoring in sport: a scoping review on available data.

There is a significant request for wearable systems for vital signs and athletic performance monitoring during sport practice, both in professional and non-professional fields. Respiratory rate is a rather neglected parameter in this field, but several studies show that it is a strong marker of physical exertion. The aim of the present scoping review is to evaluate the number and kind of existing studies on wearable technologies for the analysis of the chest wall movement for respiratory monitoring in sport and fitness. The review included studies investigating the use of contact-based wearable techniques for the detection of chest wall movement for respiratory monitoring during professional or amateur sport, during fitness and physical activity. The search was conducted on PubMed/Medline, Scopus and Google Scholar electronic databases using keywords. Data extracted were entered into a Microsoft Excel spreadsheet by the leading author and then double-checked by the second author. A total of 25 descriptive studies met the inclusion criteria. Few studies on small number of athletes were found, technologies were often evaluated without a reference system, data on participants are sometimes missing. To date, we are not able to draw conclusions on which is the best and most reliable device to use during sport practice.

Investigation of apoptosis in cultured cells infected with equine herpesvirus 1.

Many viruses alter different stages of apoptosis of infected cells as a strategy for successful infection. Few studies have addressed mechanisms of equine herpesvirus 1 (EHV-1) strain-induced cell death. We investigated the effect of an abortigenic strain (AR8 strain) on heterologous Madin-Darby bovine kidney cells and homologous equine dermis (ED) cells cell lines. We compared morphologic and biochemical features of early and late apoptosis at different postinfection times. We investigated translocation of phosphatidylserine to the cell surface, nuclear fragmentation and changes in the cytoskeleton using flow cytometry and annexin V/propidium iodide staining, DNA laddering, terminal deoxynucleotidyl transferase UTP nick-end labeling assay and immunofluorescence staining of cytokeratin 18 cleavage. AR8 EVH-1 strain interfered with apoptosis in both cell lines, particularly during the middle stage of the replication cycle; this was more evident in ED cells. Although this antiapoptotic effect has been reported for other alpha herpesviruses, our findings may help elucidate how EHV-1 improves its infectivity during its cycle.

Microvascular lesions and changes in cell proliferation and death, and cytokine expression in the placentas of mice experimentally infected with Equid Herpesvirus 1.

This study describes the changes observed in the placentas of mice experimentally infected with an abortigenic strain of EHV-1 at mid-pregnancy and euthanized at days 3 and 4 post-infection. We analyzed microscopic vascular alterations, cell proliferation and death by immunohistochemistry, and the expression of IFN-γ, TNF-α and the IL-10 by qPCR and flow cytometry. Infected mice showed slight respiratory signs and ruffled fur during the first two days post-infection. Virus isolation and DNA detection were positive only in the lungs of the infected mice. Vascular congestion, increase in the labyrinth area, and a significant reduction in fetal capillary endothelium surface of infected placentas were found. Cell proliferation was significantly reduced in the infected placentas, whereas the apoptosis was significantly increased. IL10, TNF and IFN-γ showed different expression in the infected placentas and uteri. The effects of EHV-1 during pregnancy depend on different pathogenic mechanisms in which vascular alterations, and cell death and proliferation and local cytokine changes are compromised.

Is pit and fissure sealing of buccal surfaces useful in reducing incidence of caries of first permanent molars?

AIM: The aim of the study was to establish whether caries prevalence on the buccal surfaces of first lower permanent molars (FLPMs) can be compared to those on the occlusal surfaces in order to justify the utility of extending pit and fissure sealing also to the extra-occlusal surfaces. MATERIALS AND METHODS: Design: an observational study was carried out in the children population (n=779) aged ≤14 years (mean age 7.68, SD 3.53) that presented at the Paediatric Dentistry Department of the University of Perugia. In the study were included 460 patients, and absolute frequency (number) of FLMP occlusal and buccal caries, together with their ratio and their difference in percentage, were recorded and analysed. Moreover, FLMP buccal caries variation related to age, sex and parent's nationality were calculated. RESULTS: Among the 460 children included (243 males) aged 5-14 years, 103 erupted FLPMs were analysed. Of their decayed surfaces (n=115), the occlusal surfaces were 62 (53.9%) and the buccal surfaces 53 (46.1%); the absolute frequency ratio was 1.17 and the percentage difference was 7.8%. The female gender was significantly related to buccal caries of FLPMs [OR = 2.66 (95% CI; 1.27-5.59; p=0.0096)] as was the age ranging between 10-14 years [OR = 2.73 (95% CI; 1.36-5.50; p =0.004)]. The parents nationality was not significantly related to buccal caries [Odds Ratio =1.47 (95% CI; 0.70-3.06; p = 09040)]. CONCLUSIONS: The similar caries susceptibility of buccal and occlusal surfaces of FLPMs stimulates further comparative studies about the usefulness of extending pit and fissure sealing to the buccal surfaces in addition to the occlusal prophylactic intervention, particularly with regard to the female sex and during the early eruption stages of these teeth.

Comparative analysis and quantitative evaluation of ankle-foot orthoses for foot drop in chronic hemiparetic patients.

BACKGROUND: Ankle-foot-orthoses (AFOs) are frequently prescribed for hemiparetic patients to compensate for the foot drop syndrome. However, there is not a systematic study either on the effectiveness of AFOs in the gait recovery process or pointing out the therapeutic differences among the various types of AFOs available on the market. AIM: To perform a comparative evaluation of solid and dynamic Ankle-Foot-Orthoses (AFOs) on hemiparetic patients affected by foot drop syndrome by means of spatio-temporal, kinematic and electromyographic indicators. DESIGN: Crossover design with randomization for the interventions. SETTING: A rehabilitation center for adults with neurologic disorders. POPULATION: Ten chronic hemiparetic patients with foot drop syndrome met inclusion criteria and volunteered to participate. METHODS: Biomechanical gait analysis was carried out on hemiparetic subjects with foot drop syndrome under 3 conditions with randomized sequences: 1) without AFO; 2) wearing a solid AFO; 3) wearing a dynamic AFO. Significant changes in spatio-temporal, kinematic and electromyographic features of gait were investigated. RESULTS: Gait analysis outcomes showed that there were no significant differences among the solid and the dynamic AFO on the spatio-temporal parameters. Both AFOs led to a reduction of the range of motion of the ankle dorsi-plantar-flexion during stance with respect to the ambulation without AFO. They also had the effect of reducing the asymmetry between the paretic and the contralateral limb in terms of ankle angle at initial contact and hip flexion. The solid AFO generally led to an increase of the co-contraction of the couples of muscles involved in the gait. CONCLUSION: The proposed set of indicators showed that the AFOs were capable of limiting the effect of the foot-drop in hemiparetic patients and balancing the two limbs. Main differences between the two orthoses were related to muscular activity, being the level of co-contraction of the two couples of analysed muscles typically lower when the dynamic AFO was worn and closer to a normal pattern. CLINICAL REHABILITATION IMPACT: A more extensive use of the proposed indicators in the clinical practice is expected in order to enable the definition of clinical guidelines for the prescription of the two devices.

Fulminant hepatic failure of autoimmune aetiology in children.

OBJECTIVE: Autoimmune hepatitis (AIH) is considered an underdiagnosed cause of fulminant hepatic failure (FHF). Autoimmune FHF (AI-FHF) is believed to lead invariably to liver transplantation (LTX) or death. We aimed to describe the autoimmune features of children diagnosed as having AI-FHF and indeterminate FHF (ID-FHF), and describe the outcome of patients with AI-FHF treated with immunosuppressive drugs. METHODS: In this case-control study, the files of patients with AI-FHF and ID-FHF were reviewed and compared. AIH was diagnosed based on positive autoantibodies, raised immunoglobulin G, and histology when available. FHF was defined by raised transaminases, international normalised ratio ≥ 2.0, presence of encephalopathy, and no previously recognised liver disease. RESULTS: A total of 46 children with FHF were managed in the last 15 years: 10/46 (22%) had AI-FHF, 20/46 (43%) ID-FHF, and 16 had other diagnosis. The mean follow-up time was 4.6 years. AI-FHF and ID-FHF differed for the presence of autoantibodies (10/10, 6/10 liver/kidney microsome [LKM]-type, vs 3/20, none LKM, P < 0.0001), immunoglobulin G level (1845 vs 880 mg/dL, P < 0.001), median age at diagnosis (6.4 vs 1.8 years, P = 0.017), and alanine aminotransferase level (1020 vs 2386 IU/L, P = 0.029). Liver histology did not allow to differentiate the 2 conditions. Among the patients with AI-FHF, 4/9 who received steroids recovered; 5/9 required LTX and 1 died awaiting treatment. CONCLUSIONS: AIH is a much more common cause of FHF than previously suggested, and a complete autoantibody testing including LKM-type is essential in this setting. Autoantibodies are uncommon in ID-FHF, and histology cannot distinguish it from AI-FHF. A cautious steroid trial may avoid LTX in some of the patients with AI-FHF.

Protective effects of intranasal immunization with recombinant glycoprotein d in pregnant BALB/c mice challenged with different strains of equine herpesvirus 1.

Equine herpesvirus (EHV)-1 induces respiratory infection, neurological disorders and abortion in horses. Most of the currently available attenuated or inactivated vaccines against this infection are administered intramuscularly and only provide partial protection against the respiratory disease. The present study examines the effect of intranasal immunization with purified EHV-1 recombinant glycoprotein D (gD) in BALB/c mice followed by challenge with three different EHV-1 strains during early to mid-pregnancy. The induced viral infection was evaluated by virus isolation, DNA detection by polymerase chain reaction, histopathology and immunohistochemical localization of antigen in the lung, placenta and uterus. Non-immunized mice showed clinical signs of infection, positive virus isolation from lungs and uteri, and abortion induced by one of the virus strains. Endometrial lesions developed in some of these animals that have been described previously only in horses. Immunized mice and their offspring had no viral infection or typical lesions. Intranasally administered gD therefore induced partial or complete protection against three different EHV-1 strains in BALB/c mice.

Microalgal biomass production by using ultra- and nanofiltration membrane fractions of olive mill wastewater.

Olive milling produces huge amounts of wastewater (OMWW) characterized by an extremely high organic load. Its polyphenols content is a hindrance to conventional biological treatment and to using it as growing medium for common microbial biomasses. The practice to dump it on soil is in conflict with the latest EU directives about waste management. OMWW can be effectively and efficiently treated by means of membrane technology to a fraction of the initial volume, but membrane processing concentrates still require treatment. Reversing the overall cost balance of membrane processing and subsequent treatment requires valorizing the concentrates through their reuse, as well as ensuring long-term service of the membrane system through effective wastewater pretreatment and sustainable, fouling-controlling, membrane operation conduite. Aim of this work is to reuse and valorize the ultra- and nanofiltration membrane concentrates as media for biomass production of microalgae and cyanobacteria. Scenedesmus dimorphus and Arthrospira platensis, usable as a food, feed, nutraceutical component or feedstock for biofuels, were selected for this investigation. Microalgal growth was experimentally determined and related to the composition of the concentrate-based media and to the irradiance distribution within the photobioreactor volume to decouple light limitation and medium chemical composition effects.

Inter-hemispheric coupling changes associate with motor improvements after robotic stroke rehabilitation.

PURPOSE: In the chronic phase of stroke brain plasticity plays a crucial role for further motor control improvements. This study aims to assess the brain plastic reorganizations and their association with clinical progresses induced by a robot-aided rehabilitation program in chronic stroke patients. METHODS: 7 stroke patients with an upper limb motor impairment in chronic phase underwent a multi-modal evaluation before starting and at the end of a 12-week upper-limb neurorehabilitation program. Fugl-Meyer Assessment (FMA) Scale scores and performance indices of hand movement performance (isometric pinch monitored through a visual feedback) were collected. Cerebral reorganizations were characterized by 32-channel electroencephalography (EEG) focusing on ipsilesional and contralesional resting state properties investigating both bipolar derivations overlying the middle cerebral artery territory and the primary somatosensory sources (S1) obtained through the Functional Source Separation (FSS) method. Power Spectral Density (PSD) and interhemispheric coherence (IHCoh) at rest were measured and correlated with clinical and hand control robot-induced improvements. RESULTS: After the robotic rehabilitation we found an improvement of FMAS scores and hand motor control performance and changes of brain connectivity in high frequency rhythms (24-90 Hz). In particular, the improvement of motor performance correlated with the modulation of the interhemispheric S1 coherence in the high beta band (24-33 Hz). CONCLUSIONS: Recently it has been shown that an upper limb robot-based rehabilitation improves motor performance in stroke patients. We confirm this potential and demonstrate that a robot-aided rehabilitation program induces brain reorganizations. Specifically, interhemispheric connectivity between primary somatosensory areas got closer to a 'physiological level' in parallel with the acquisition of more accurate hand control.

Intestinal transplantation in children: the first successful Italian series.

The preliminary experience of the first Italian program of pediatric intestinal transplantation is presented herein. A multidisciplinary group with broad experience in pediatric solid organ transplantation started the program. Nine children with complications of chronic intestinal failure were listed for transplantation. One child died on the waiting list; one received an isolated liver transplantation; three isolated intestinal; three multivisceral; and one, a combined liver/intestine transplantation. There was no in-hospital mortality, and all children were weaned from parenteral nutrition. The recipient of the multivisceral graft died after 14 months for unknown causes. All other recipients are alive after a median follow-up of 13 months. Patient and graft actuarial survivals for recipients of intestinal grafts were 100% at 1 year and 75% at 2 years.

Performance of a fungal based SBR under pH extreme and shock phenolic exposure.

An investigation was performed to explore the capabilities of a filamentous fungal biomass to grow non-aseptically in a glucose-fed Sequencing Batch Reactor system in very extreme environment (pH 3.5) conditions. Trichoderma viride Pers: Fr. Isolate 8/90 was used as inoculum. Microscopic investigations were carried out to confirm fungal dominance in the open culture. In batch tests, the fungal biomass showed a significant ability to grow and remove the applied organic load (2000 mg(Glucose) L(-1) d(-1)), with high biomass yields. Furthermore, the biomass showed an ability to resist gallic acid toxicity at high concentraions (1 g L(-1)) without any pre- exposure acclimation of the biomass. The biomass (about 2.5 g(VSS) L(-1)) demonstrated significant aerobic removal of gallic acid in a timeframe of 20 h from initial exposure. The robust characteristics of this SBR system demonstrate potential for future development of fungal based treatment for recalcitrant feedstocks or operation under extreme environmental conditions.

Cyclosporin in steroid-resistant autoimmune hepatitis and HCV-related liver diseases.

Cyclosporin has been used for many years in transplantation, and in this field its role is widely documented. However, other fields of application merit to be investigated, including the role of cyclosporin in treating autoimmune hepatitis and its possible role as an antiviral agent in hepatitis C virus (HCV) infections in both immunocompetent patients and in recipients of orthotopic liver transplants. Cyclosporin A has given promising results in small studies, and experience in transplantation and other immunological disorders indicates that its side-effects can be adequately managed. Cyclosporin certainly deserves further clinical investigation for first-line therapy in autoimmune hepatitis. Cyclosporin A suppresses the HCV genome dose-dependently in vitro at clinically relevant concentrations (150-250 ng/mL). The maximum effect is similar to that obtained with IFN alpha, and the effects of these two agents are certainly additive, and possibly synergistic. The inhibitory action of cyclosporin A appears to be independent upon its immunosuppressive action. Analysis of indirect endpoints in clinical trials on cyclosporin A for immunosuppression in transplant recipients indicates that cyclosporin A treatment can delay recurrence of HCV. Small, open label studies suggest that the observed anti-HCV activity of cyclosporin A can be translated into a real clinical benefit; nevertheless, these findings need to be confirmed in randomized, controlled clinical trials.