One year of surgical mask testing at the University of Bologna labs: Lessons learned from data analysis.

The outbreak of SARS-CoV-2 pandemic highlighted the worldwide lack of surgical masks and personal protective equipment, which represent the main defense available against respiratory diseases as COVID-19. At the time, masks shortage was dramatic in Italy, the first European country seriously hit by the pandemic: aiming to address the emergency and to support the Italian industrial reconversion to the production of surgical masks, a multidisciplinary team of the University of Bologna organized a laboratory to test surgical masks according to European regulations. The group, driven by the expertise of chemical engineers, microbiologists, and occupational physicians, set-up the test lines to perform all the functional tests required. The laboratory started its activity on late March 2020, and as of the end of December of the same year 435 surgical mask prototypes were tested, with only 42 masks compliant to the European standard. From the analysis of the materials used, as well as of the production methods, it was found that a compliant surgical mask is most likely composed of three layers, a central meltblown filtration layer and two external spunbond comfort layers. An increase in the material thickness (grammage), or in the number of layers, does not improve the filtration efficiency, but leads to poor breathability, indicating that filtration depends not only on pure size exclusion, but other mechanisms are taking place (driven by electrostatic charge). The study critically reviewed the European standard procedures, identifying the weak aspects; among the others, the control of aerosol droplet size during the bacterial filtration test results to be crucial, since it can change the classification of a mask when its performance lies near to the limiting values of 95 or 98%.

Immune Response and Partial Protection against Heterologous Foot-and-Mouth Disease Virus Induced by Dendrimer Peptides in Cattle.

Synthetic peptides mimicking protective B- and T-cell epitopes are good candidates for safer, more effective FMD vaccines. Nevertheless, previous studies of immunization with linear peptides showed that they failed to induce solid protection in cattle. Dendrimeric peptides displaying two or four copies of a peptide corresponding to the B-cell epitope VP1 [136-154] of type O FMDV (O/UKG/11/2001) linked through thioether bonds to a single copy of the T-cell epitope 3A [21-35] (termed B2T and B4T, resp.) afforded protection in vaccinated pigs. In this work, we show that dendrimeric peptides B2T and B4T can elicit specific humoral responses in cattle and confer partial protection against the challenge with a heterologous type O virus (O1/Campos/Bra/58). This protective response correlated with the induction of specific T-cells as well as with an anamnestic antibody response upon virus challenge, as shown by the detection of virus-specific antibody-secreting cells (ASC) in lymphoid tissues distal from the inoculation point.

Individual analysis of patients with HoFH participating in a phase 3 trial with lomitapide: The Italian cohort.

BACKGROUND AND AIMS: The efficacy and safety of lomitapide as adjunct treatment for adults with homozygous familial hypercholesterolaemia (HoFH) have been confirmed in a phase 3 trial. Given the small number of patients (N = 29), and variations in patient characteristics, examining individual cases provides additional details regarding patient management with lomitapide. Here, we examine the details of the Italian patient cohort in the phase 3 trial. METHODS AND RESULTS: The methodology of the multinational, single-arm, open-label, 78-week, dose-escalation, phase 3 trial has been previously reported. The current report details the Italian cohort of six patients (three males, three females) based on individual patient data, individual patient histories and narratives, and by mean data ± SD. Lomitapide was administered according to the dose-escalation protocol. At Week 78, concentrations of low-density lipoprotein-cholesterol were decreased by a mean of 42.6 ± 21.8% compared with baseline. Lomitapide was similarly well tolerated in the Italian cohort as in the entire study population. The most common adverse events were gastrointestinal symptoms. One patient showed an increase in liver transaminases >5× upper limit of normal that resolved after lomitapide treatment was reduced and maintained at a lower dose. CONCLUSION: The efficacy, safety and tolerability of lomitapide demonstrated in the Italian subgroup of patients are consistent with findings in the entire study population, and illustrate the broad applicability of lomitapide therapy across genotypes and clinical phenotypes. These data also provide an insight into the management of lomitapide use in a cohort of patients within a clinical trial protocol. Clinicaltrials.gov Identifier: NCT00730236.

Systemic Foot-and-Mouth Disease Vaccination in Cattle Promotes Specific Antibody-Secreting Cells at the Respiratory Tract and Triggers Local Anamnestic Responses upon Aerosol Infection.

UNLABELLED: Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting biungulate species. Commercial vaccines, formulated with inactivated FMD virus (FMDV), are regularly used worldwide to control the disease. Here, we studied the generation of antibody responses in local lymphoid tissues along the respiratory system in vaccinated and further aerosol-infected cattle. Animals immunized with a high-payload monovalent FMD vaccine developed high titers of neutralizing antibodies at 7 days postvaccination (dpv), reaching a plateau at 29 dpv. FMDV-specific antibody-secreting cells (ASC), predominantly IgM, were evident at 7 dpv in the prescapular lymph node (LN) draining the vaccination site and in distal LN draining the respiratory mucosa, although in lower numbers. At 29 dpv, a significant switch to IgG1 was clear in prescapular LN, while FMDV-specific ASC were detected in all lymphoid tissues draining the respiratory tract, mostly as IgM-secreting cells. None of the animals (n = 10) exhibited FMD symptoms after oronasal challenge at 30 dpv. Three days postinfection, a large increase in ASC numbers and rapid isotype switches to IgG1 were observed, particularly in LN-draining virus replication sites already described. These results indicate for the first time that systemic FMD vaccination in cattle effectively promotes the presence of anti-FMDV ASC in lymphoid tissues associated with the respiratory system. Oronasal infection triggered an immune reaction compatible with a local anamnestic response upon contact with the replicating FMDV, suggesting that FMD vaccination induces the circulation of virus-specific B lymphocytes, including memory B cells that differentiate into ASC soon after contact with the infective virus. IMPORTANCE: Over recent decades, world animal health organizations as well as national sanitary authorities have supported the use of vaccination as an essential component of the official FMD control programs in both endemic and disease-free settings. Very few works studied the local immunity induced by FMD vaccines at the respiratory mucosa, and local responses induced in vaccinated animals after aerosol infection have not been described yet. In this work, we demonstrate for the first time that systemic FMD vaccination (i) induced the early presence of active antigen-specific ASC along the respiratory tract and (ii) prompted a rapid local antibody response in the respiratory mucosa, triggered upon oronasal challenge and congruent with a memory B-cell response. This information may help to understand novel aspects of protective responses induced by current FMD vaccines as well as to provide alternative parameters to establish protection efficiency for new vaccine developments.

The lipid-lowering effects of lomitapide are unaffected by adjunctive apheresis in patients with homozygous familial hypercholesterolaemia - a post-hoc analysis of a Phase 3, single-arm, open-label trial.

OBJECTIVE: Lomitapide (a microsomal triglyceride transfer protein inhibitor) is an adjunctive treatment for homozygous familial hypercholesterolaemia (HoFH), a rare genetic condition characterised by elevated low-density lipoprotein-cholesterol (LDL-C), and premature, severe, accelerated atherosclerosis. Standard of care for HoFH includes lipid-lowering drugs and lipoprotein apheresis. We conducted a post-hoc analysis using data from a Phase 3 study to assess whether concomitant apheresis affected the lipid-lowering efficacy of lomitapide. METHODS: Existing lipid-lowering therapy, including apheresis, was to remain stable from Week -6 to Week 26. Lomitapide dose was escalated on the basis of individual safety/tolerability from 5 mg to 60 mg a day (maximum). The primary endpoint was mean percent change in LDL-C from baseline to Week 26 (efficacy phase), after which patients remained on lomitapide through Week 78 for safety assessment and further evaluation of efficacy. During this latter period, apheresis could be adjusted. We analysed the impact of apheresis on LDL-C reductions in patients receiving lomitapide. RESULTS: Of the 29 patients that entered the efficacy phase, 18 (62%) were receiving apheresis at baseline. Twenty-three patients (13 receiving apheresis) completed the Week 26 evaluation. Of the six patients who discontinued in the first 26 weeks, five were receiving apheresis. There were no significant differences in percent change from baseline of LDL-C at Week 26 in patients treated (-48%) and not treated (-55%) with apheresis (p = 0.545). Changes in Lp(a) levels were modest and not different between groups (p = 0.436). CONCLUSION: The LDL-C lowering efficacy of lomitapide is unaffected by lipoprotein apheresis.

Heterogeneity in the Antibody Response to Foot-and-Mouth Disease Primo-vaccinated Calves.

Foot-and-mouth disease (FMD) vaccines are routinely used as effective control tools in large regions worldwide and to limit outbreaks during epidemics. Vaccine-induced protection in cattle has been largely correlated with the FMD virus (FMDV)-specific antibodies. Genetic control of cattle immune adaptive responses has been demonstrated only for peptide antigens derived from FMDV structural proteins. Here, we quantify the heterogeneity in the antibody response of cattle primo-vaccinated against FMD and study its association with the genetic background in Holstein and Jersey sires. A total of 377 FMDV-seronegative calves (122 and 255 calves from 16 and 15 Holstein and Jersey sires, respectively) were included in the study. Samples were taken the day prior to primo-vaccination and 45 days post-vaccination (dpv). Animals received commercial tetravalent FMD single emulsion oil vaccines formulated with inactivated FMDV. Total FMDV-specific antibody responses were studied against three viral strains included in the vaccine, and antibody titres were determined by liquid-phase blocking ELISA. Three linear hierarchical mixed regression models, one for each strain, were formulated to assess the heterogeneity in the immune responses to vaccination. The dependent variables were the antibody titres induced against each FMDV strain at 45 dpv, whereas sire's 'breed' was included as a fixed effect, 'sire' was included as a random effect, and 'farm' was considered as a hierarchical factor to account for lack of independence of within herd measurements. A significant association was found between anti-FMDV antibody responses and sire's breed, with lower immune responses found in the Jersey sires' offspring compared with those from Holstein sires. No significant intrabreed variation was detected. In addition, farm management practices were similar in this study, and results of the serological assays were shown to be repeatable. It therefore seems plausible that differences in the immune response may be expected in the event of a mass vaccination campaigns.

Early adaptive immune responses in the respiratory tract of foot-and-mouth disease virus-infected cattle.

Foot-and-mouth disease (FMD) is a highly contagious viral disease which affects both domestic and wild biungulate species. This acute disease, caused by the FMD virus (FMDV), usually includes an active replication phase in the respiratory tract for up to 72 h postinfection, followed by hematogenous dissemination and vesicular lesions at oral and foot epithelia. The role of the early local adaptive immunity of the host in the outcome of the infection is not well understood. Here we report the kinetics of appearance of FMDV-specific antibody-secreting cells (ASC) in lymphoid organs along the respiratory tract and the spleen in cattle infected by aerosol exposure. While no responses were observed for up to 3 days postinfection (dpi), all animals developed FMDV-ASC in all the lymphoid organs studied at 4 dpi. Tracheobronchial lymph nodes were the most reactive organs at this time, and IgM was the predominant isotype, followed by IgG1. Numbers of FMDV-ASC were further augmented at 5 and 6 dpi, with an increasing prevalence in upper respiratory organs. Systemic antibody responses were slightly delayed compared with the local reaction. Also, IgM was the dominant isotype in serum at 5 dpi, coinciding with a sharp decrease of viral RNA detection in peripheral blood. These results indicate that following aerogenous administration, cattle develop a rapid and vigorous genuine local antibody response throughout the respiratory tract. Time course and isotype profiles indicate the presence of an efficient T cell-independent antibody response which drives the IgM-mediated virus clearance in cattle infected by FMDV aerosol exposure.

The lipid- and lipoprotein- [LDL-Lp(a)] apheresis techniques. Updating.

Therapeutic plasmapheresis allows the extracorporeal removal of plasmatic lipoproteins (Lipid-apheresis) (LA). It can be non selective (non specific), semi - selective or selective low density lipoprotein-lipoprotein(a) (specific [LDL- Lp(a)] apheresis) (Lipoprotein apheresis, LDLa). The LDL removal rate is a perfect parameter to assess the system efficiency. Plasma-Exchange (PEX) cannot be considered either specific nor, selective. In PEX the whole blood is separated into plasma and its corpuscular components usually through centrifugation or rather filtration. The corpuscular components mixed with albumin solution plus saline (NaCl 0.9%) solution at 20%-25%, are then reinfused to the patient, to substitute the plasma formerly removed. PEX eliminates atherogenic lipoproteins, but also other essential plasma proteins, such as albumin, immunoglobulins, and hemocoagulatory mediators. Cascade filtration (CF) is a method based on plasma separation and removal of plasma proteins through double filtration. During the CF two hollow-fiber filters with pores of different diameter are used to eliminate the plasma components of different weight and molecular diameter. A CF system uses a first polypropylene filter with 0.55 µm diameter pores and a second one of diacetate of cellulose with 0.02 µm pores. The first filter separates the whole blood, and the plasma is then perfused through a second filter which allows the recovery of molecules with a diameter lower than 0.02 µm, and the removal of molecules larger in diameter as apoB100-containing lipoproteins. Since both albumin and immunoglobulins are not removed, or to a negligible extent, plasma-expanders, substitution fluids, and in particular albumin, as occurs in PEX are not needed. CF however, is characterized by lower selectivity since removes also high density lipoprotein (HDL) particles which have an antiatherogenic activity. In the 80's, a variation of Lipid-apheresis has been developed which allows the LDL-cholesterol (LDLC) (-61%) and Lp(a) (-60%) removal from plasma through processing 3 liters of filtered plasma by means of lipid-specific thermofiltration, LDL immunoadsorption, heparin-induced LDL precipitation, LDL adsorption through dextran sulphate. More recently (90's) the DALI®, and the Liposorber D® hemoperfusion systems, effective for apoB100- containing lipoproteins removal have been developed. All the above mentioned systems are established LDL-apheresis techniques referable to the generic definition of LDLa. However, this last definition cannot describe in an appropriate manner the removal of another highly atherogenic lipoprotein particle: the Lp(a). Thus it would be better to refer the above mentioned techniques to the wider scientific and technical concept of lipoprotein apheresis.

New clinical perspectives of hypolipidemic drug therapy in severe hypercholesterolemia.

Patients with homozygous familial hypercholesterolemia (HoFH) represent the most severe patients within the spectrum of dyslipidemias. Untreated Low-Density Lipoprotein Cholesterol (LDL-C) levels in these patients are usually in the range 500 to 1200 mg/dL. Moreover, these patients exhibit a scarce responsiveness or even non responsiveness to oral lipid lowering agents. Patients with heterozygous familial hypercholesterolemia (HetFH) tend to have untreated LDL-C levels of 250-500 mg/dL. Many of these patients are responsive to 3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA-reductase) inhibitors (statins) and/or other specific drugs. Unfortunately, a significant subset of these patients (5-10%) have a severe and/or refractory form of HetFH and after current maximal oral therapy, they remain significantly far from treatment goals (The National Cholesterol Education Program (NCEP) ATPIII guidelines). This would be defined as LDL-C levels of ≥ 190 mg/dL - prior Coronary Heart Disease (CHD) or CHD equivalent - or ≥ 250 mg/dL (no prior CHD or CHD risk-equivalent). The only current therapy option for these patients is Low Density Lipoprotein-apheresis (LDL_a). While LDL_a is very effective in reducing LDL-C, many patients do not receive this extracorporeal therapy because of costs and limited availability of LDL_a centers. Recently, new potent lipid-lowering drugs have been developed and are currently under investigation. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a critical role controlling the levels of LDL-C. Studies have demonstrated that PCSK9 acts mainly by enhancing degradation of the Low-Density Lipoprotein receptor (LDLR) protein in the liver. Inactivation of PCSK9 in mice reduces plasma cholesterol levels. Since the loss of a functional PCSK9 in human is not associated with apparent deleterious effects, this protease is becoming an attractive target for lowering plasma LDL-C levels either alone or in combination with statins. Mipomersen, an apolipoprotein B (ApoB) synthesis inhibitor, for lowering of LDL-C showed to be an effective therapy to reduce LDL-C concentrations in patients with HoFH who are already receiving lipid-lowering drugs, including high-dose statins. Lomitapide is a potent inhibitor of microsomal triglyceride transfer protein and is highly efficacious in reducing LDL-C and triglycerides (TG). Lomitapide is currently being developed for patients with HoFH at doses up to 60 mg/d. These new powerful lipid-lowering drugs might be possibly superior than available hypolipidemic agents. Their mechanisms of action, effectiveness, safety, and indication in severe, genetically determined dyslipidemias, are reviewed.

Family relations and eating disorders. The effectiveness of an integrated approach in the treatment of anorexia and bulimia in teenagers: results of a case-control systemic research.

This article presents the results of a broader clinical research into the effectiveness of integrated treatments in teenage eating disorders, carried out at the Complex Operative Unit of Psychotherapy (Unità Operativa Complessa or U.O.C.) of the Department of Psychiatric Sciences and Psychological Medicine in collaboration with the Department of Neuropsychiatric Science for Child Development (Dipartimento di Scienze Neuropsichiatriche dell'Età Evolutiva), both at the "La Sapienza" University of Rome. The hypothesis of this research project is that in diagnosticable situations such as anorexia or bulimia, an integrated and multidisciplinary treatment, which combines medical-nutritional interventions and family psychotherapy, allows better results than a single kind of treatment, which is the usual medical- nutritional intervention supported by psychiatric counselling. Twenty-eight cases (16 of bulimia and 12 of anorexia) were selected and then subdivided, with a randomized distribution, into two (experimental and control) homogeneous groups of 14 patients. The grouping variables were the diagnosis, the disorder's seriousness and duration, BMI, gender, age, family composition and social status. The variables which have been examined in this article are the clinical parameters, which were valuated in accordance with the DSM IV-TR criteria, and relational parameters which were explored through the use of the W.F.T. Test (Wiltwyck Family Tasks). These parameters were tested at beginning as well as at the end of the therapies, in both the experimental group and the control group. Statistical analysis has shown that the experimental group, which was followed with the integrated treatment, experienced a significant improvement of the parameters as related to dysfunctional family interaction modalities, and that this improvement was correlated to the positive evolution of the clinical parameters. This improvement was not present or not of the same degree in the control group. The results, moreover, demonstrate the effectiveness of an integrated systemic treatment based on a complex approach compared to a reductionist approach.

Cassia angustifolia extract is not hepatotoxic in an in vitro and in vivo study.

BACKGROUND: Cassia angustifolia L. (senna) is traditionally used as a laxative. Its major components are sennosides that are responsible for the laxative effect. Senna is recommended for the short-term treatment of acute constipation. Nevertheless people use its preparations as self-medication, often for long periods, to treat chronic constipation thus exposing themselves to adverse reactions. Most reactions were associated with hepatotoxicity. AIMS: The present study was aimed to evaluate the toxicity of a C. angustifolia leafextract (standardized at 60% of sennosides) on rat liver cells and the long-term effects on liver functions, in Wistar rats. METHODS: Cytotoxicity was assessed in a buffalo normal rat liver cell line (BRL-3A) by the trypan blue assay and the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide reduction test. In vivo effects were observed after oral administration of the extract for 4 or 8 weeks at doses of 12 and 58 mg/kg/day. At the end of treatment, animals were sacrificed, the postmortem examination was performed and serum was used for biochemical analysis. Liver samples were used for histomorphological and immunohistochemical examination along with the determination of oxidative stress parameters. RESULTS AND CONCLUSION: In BRL-3A cells, the extract was cytotoxic at concentrations that appear largely higher than those attainable in humans. In Wistar rats, the extract did not induce any significant change in all of the parameters tested. In summary, the present study indicates a lack of hepatotoxicity of senna at doses higher than those generally used in humans.

Role of macrophages in early protective immune responses induced by two vaccines against foot and mouth disease.

Foot and Mouth Disease (FMD) is an acute disease of cloven-hoofed species. We studied the protection and early immune response induced in the murine model by vaccines formulated with inactivated virus and two different adjuvants. The presence of IMS12802PR or ISA206VG adjuvants yielded protection against viral challenge at early times post vaccination and induced FMDV-specific, but non neutralizing, antibody titers. In vivo macrophage depletion in vaccinated mice severely decreased the protection levels after virus challenge, indicating a central role of this cell population in the response elicited by the vaccines. Accordingly, opsonophagocytosis of FITC-labelled virus was augmented in 802-FMDVi and 206-FMDVi vaccinated mice. These results demonstrate the ability of the studied adjuvants to enhance the protective responses of these inactivated vaccines without the increase in seroneutralizing antibodies and the main role of opsonization and phagocytosis in the early protective immune responses against FMD infection in the murine model.

Timing clinical events in the treatment of pancreatitis and hypertriglyceridemia with therapeutic plasmapheresis.

BACKGROUND: Hyperlipidemic pancreatitis (HP) is caused by severe hypertriglyceridemia (SHTG). Evidence of SHTG refractoriness to standard medical treatment but not to therapeutic apheresis has increased in the last years. METHODS: Described is the timing of clinical events and the sequence of therapeutic plasma-exchange (TPE) procedures to treat pancreatitis due to SHTG in a male patient, Caucasian, aged 49years, referred to emergency for severe epigastric pain. There was no history of alcohol consumption, a pre-existing mild hyperlipidemia was treated with diet alone, and biliary imaging was normal. Physical examination revealed epigastric tenderness. Laboratory investigation revealed marked hypertriglyceridemia (11,355mg/dL; range: 30-150), and hypercholesterolemia (941mg/dL; range: 80-200). Serum amylase (Amy) and lipase (Lip) were increased: 160UI/L (range: 20-100) and 175UI/L (range: 13-60), respectively. A computerized tomography (CT) scan of the abdomen revealed a picture compatible with acute pancreatic phlogosis. It was diagnosed as "acute secondary pancreatitis (AP) and SHTG". RESULTS: The patient was successfully submitted to three sessions of TPE in emergency. He was released from hospital after 13 days of hospitalization. The levels of lipids and lipoproteins in his plasma were as follows: triglycerides (TG) 185mg/dL; total cholesterol (TC) 179mg/dL; HDL-cholesterol (HDLC) 22mg/dL; LDL-cholesterol (LDLC) 120mg/dL. CONCLUSIONS: The decision to submit the patient with clinical evidence of HP caused by SHTG to apheresis was correct. The improvement in the clinical picture was fast and the recovery was complete.

Cytokines profile in serum of homozygous familial hypercholesterolemia is changed by LDL-apheresis.

OBJECTIVE: The effects of LDL-apheresis (LDLa) with dextran sulphate on plasma cytokines in 6 homozygous familial hypercholesterolemic (HozFH) patients, were evaluated. METHODS: Plasma IL-1α; IL-1ra; IL-4; IL-6; IL-10; IL-12(p40); IL-12(p70); TNF-α, sTNF-R, VEGF, VEGF-R1, E-Selectin (ESEL), and P-Selectin (PSEL) concentrations were measured before and after LDLa on three consecutive sessions for each patient. RESULTS: TNF-α was significantly reduced (-60%; P=0.01), while TNF-R was only slightly increased (+15%), although not significantly. Plasma VEGF was significantly reduced (-57%; P=1.87301E-05), while VEGF-R1 was significantly increased (+56%; P=0.05). ESEL and PSEL were reduced but not to a statistically significant extent (-19%, -15%, respectively). IL-1α level was dramatically reduced (-87%; P=0.0001). IL-1ra concentration was only slightly increased in plasma, but not significantly. IL-4 and IL-10 levels were significantly reduced in plasma after apheresis (-50%; P=0.03, and -55%; P=0.004, respectively). On the contrary, IL-6 concentration showed a slight decrease (-8%). Plasma IL-12p40 was significantly increased (+47%; P=0.0004). On the other hand, IL-12p70 was reduced, but the difference (-31%) was not statistically significant. CONCLUSIONS: Plasma cytokines imbalance is associated with inflammation and atherogenesis. In this study LDLa changed several circulating cytokines inducing anti-inflammatory and anti-atherogenic changes in cytokines plasma profile in HozFH patients with/without pre-existing angiographically demonstrated coronary heart disease (CHD) and aortic valvular disease (AVD).

Adjuvant effect of Cliptox on the protective immune response induced by an inactivated vaccine against foot and mouth disease virus in mice.

Foot and Mouth Disease (FMD) is an acute disease caused by Foot and Mouth Disease Virus (FMDV) which causes important economy losses, this is why it is necessary to obtain a vaccine that stimulates a rapid and long-lasting protective immune response. Cliptox is a mineral microparticle that in earlier studies has shown adjuvant activity against different antigens. In this study we have examined the effects of Cliptox on the magnitude and type of immunity elicited in response to inactivated FMDV (iFMDV) vaccine. It was demonstrated that iFMDV-Cliptox stimulates a specific antibody response detected in mucosal and in sera. The different isotype profiles elicited by inoculation with this vaccine indicate a Th1/Th2 response. Also, an increase in dendritic cells and macrophages in the spleen in comparison with the iFMDV vaccine iFMDV-Cliptox was detected. The Cliptox-iFMDV formulation was non toxic by using egg embryos and yielded increased protection against challenge with FMDV in the murine model. Our results show that the incorporation of Cliptox into FMDVi vaccine induces an increase of the specific protective immune response in mice and clearly indicate that Cliptox TM exert an (important) up-regulation on DC and MPhi. Additionally, Cliptox TM adjuvant can be used in vaccines for induction of mucosal immune response.

Treatment of symptomatic hyperLp(a)lipidemia with LDL-apheresis vs. usual care.

BACKGROUND/AIMS: To assess LDL-apheresis efficacy to lower Lp(a) and to compare the effects of Usual Medical Care (UMC) a 12-months study was carried out. The incidence of new coronary artery disease (CAD) events/need of revascularization, was also monitored. METHODS: Twenty-one patients with hyperLp(a)lipidemia and angiographically documented CAD were randomly assigned to LDL-apheresis every week, or the UMC. RESULTS: LDL-apheresis group, averaged an Lp(a) reduction of 57.8+/-9.5% vs. basal values (P<0.001). In the UMC group Lp(a) increased in 1 year to 14.7+/-36.5% (P=0.66). Stepwise multivariate regression analysis for predictors of Lp(a) including: type of treatment, smoking, hypertension, age, age at first cardiovascular event, initial Lp(a), LDL, and BMI values, was performed. Only the type of treatment was co-related (P<0.001): Lp(a) variation (beta)=0.863. The model has R2 adjusted relative risk of 0.725. CONCLUSION: LDL-apheresis could be the first line treatment of isolated hyperLp(a)lipidemia when CAD is established. New CAD events/cardiac interventions were not observed.

Treatment of symptomatic HyperLp(a)lipoproteinemia with LDL-apheresis: a multicentre study.

LDL-apheresis (LDLa) efficacy in the treatment of symptomatic HyperLp(a)lipoproteinemia -HyperLp(a)- has been studied in a multicentre trial. After 3.1+/-2.7 years of weekly and biweekly treatment, the data from 19 patients (males:12; females:7; aged 53.8+/-9.3 years; mean body mass index: 24.6+/-2.3 Kg/m²) were evaluated. Data were collected using the same questionnaire shared by 5 participating centres. A total of 2331 procedures were performed. A mean of 3593.7+/-800.3 ml of plasma or 8115.3+/-2150.1 ml of blood, depending upon the technique used (H.E.L.P., D.A.LI., Dextransulphate, Lipocollect 200), was regularly treated on average every 10.1+/-2.6 days. Baseline mean Lp(a) levels were 172.3+/-153.8 mg/dL. The mean pre-/post-apheresis Lp(a) levels decreased from 124.5+/-107.2 mg/dL (p<0.001 vs baseline) to 34.2+/-40.6 mg/dL (p<0.001 vs pre-). Baseline mean LDL-cholesterol (LDLC) levels were 152.3+/-74.6 mg/dL. The mean pre-/post-apheresis LDLC levels decreased from 130.4+/-61.1 mg/dL (p<0.004 vs baseline) to 41.2+/-25.1 mg/dL (p<0.001 vs pre-). The hypolipidemic drugs given to the patients during LDLa were: ezetimibe+simvastatin, atorvastatin, rosuvastatin, pravastatin, acipimox, and omega-3 fatty acids. 58% of the patients had arterial hypertension. Cigarette smokers were 5.3%. Alcohol intake was present in 21%. 52.6% were physically active. Patients with coronary artery disease (CAD) submitted to coronary catheterization before LDLa were 95%. In 5.5% (#1) CAD recurred despite treatment with LDLa. 79% were submitted to coronary revascularization before LDLa. CAD was: monovasal in 8 patients (42.1%), bivasal in 5 (26.4%), trivasal in 4 (21%), plurivasal in 2 (10.5%). In 94.5% of the sample the lesions were stable (< 0% deviation) over 3.1+/-2.7 years. 37% had both CAD and extra-coronary artery disease. This multicentre study confirmed that long-term treatment with LDLa was at least able to stabilize CAD in the majority of the individuals with symptomatic HyperLp(a).

Therapeutic apheresis in low weight patients: technical feasibility, tolerance, compliance, and risks.

The use of therapeutic apheresis in very low weight patients is generally thought to have limitations, because of possible severe adverse reactions, potential risk related to the extracorporeal procedure, due to the low weight of the young patients. A careful therapeutic approach using appropriate precautions, and also introducing modifications to the standard procedure, can minimise the risk without compromising the efficacy of the plasmapheresis. The aim of the study was to evaluate apheresis tolerance and acceptability in children [Artif. Organs. 21 (1997) 1126] and infants [J. Clin. Apheresis 5 (1989) 21] with inherited lipid metabolism disorder, familial hypercholesterolemia (FH), primary hyperlipoproteinemia (lipoprotein phenotype I), and acute leukemia, weighing on average 20.55 kg. One thousand one hundred twenty three aphereses were completed. Three types of apheresis were performed: leukapheresis, plasma exchange, dextran sulphate cellulose (DSC) low density lipoprotein (LDL)-apheresis. Three different types of continuous flow systems were used. Technical adaptation depending on patients blood volume, body mass index, hematocrit, type of system used, permitted us to perform complete aphereses, obtaining a high degree of tolerance and acceptability of the treatment. The use of plasmapheresis is regarded to be an extreme therapeutic measure in children. However, when the need for such treatment is undebatable, plasmapheresis must be done. A well-trained and experienced team can overcome the technical difficulties in order to complete the procedures without complications. The most frequently observed adverse effects are vascular relative access insufficiency (2.0%), and mild hypotension (2.0%).

Efficacy, safety and tolerability of combined low-dose simvastatin-fenofibrate treatment in primary mixed hyperlipidaemia.

OBJECTIVE: In order to assess the long-term (12 months) efficacy and safety of fenofibrate administered with simvastatin in the treatment of primary mixed hyperlipidaemia, we conducted a study that compared increasing dosages of these drugs in subgroups of men and women belonging to a clinical sample of out-patients. DESIGN: This was an open study carried out in patients with primary mixed hyperlipidaemia (lipoprotein phenotype IIb) who needed a combined therapeutic approach because of their poor response to a single-drug regimen with an HMG-CoA reductase inhibitor (simvastatin). Thus, a fibrate (fenofibrate) was added to the therapy. The study lasted 12 months. PATIENTS: Forty-five patients (mean age: 58.9 +/- 11.3 years) with primary mixed hyperlipidaemia who showed a poor response to the single-drug hypolipidaemic treatment were enrolled. Their average plasma triglyceride level was consistently above 300 mg/dL and low-density lipoprotein cholesterol (LDL-C) was over 160 mg/dL after at least 6 months of a single hypolipidaemic drug (simvastatin) regimen plus antiatherogenic dietary treatment. INTERVENTIONS: Five patients received simvastatin 10mg once daily in addition to fenofibrate 200mg; 26 patients received simvastatin 20mg once daily plus fenofibrate 200mg; 11 patients received simvastatin 20mg once daily plus fenofibrate 300mg; and three patients received simvastatin 30mg once daily plus fenofibrate 200mg. The patients were allocated to treatment groups on the basis of their relative response to the therapy. Those making up the progressively higher agent/dose groups were the individuals at higher cardiovascular risk according to the total cholesterol and non-high-density lipoprotein cholesterol (HDL-C) values. RESULTS: The double-drug regimen given for 12 months to four different groups, according to the different combined dosages of simvastatin and fenofibrate, resulted in a reduction in total cholesterol of 18% (p