Public health and clinical approach to proactive Prevalence of symptoms-based diagnosis of mild SARS-CoV-2 infection in southern Tuscany.

BACKGROUND: To date, it is unknown how many Italians have had or have a mild SARS-CoV-2 infection, because of the lack of epidemiological studies involving the general population. STUDY DESIGN: Aim of this study was to investigate the prevalence/incidence of a symptoms-based mild SARS-CoV-2 infection in southern Tuscany, by using an online survey. METHODS: An anonymous random middle-aged sample of 3,460 individuals completed the survey. A symptom-score ≥5, calculated on 195 patients with RT-PCR COVID-19 disease (sensitivity/specificity of 0.815/0.780 respectively) was used for the diagnosis. RESULTS: This cut-off highlighted that 12.3% of all the population might have had a SARS-CoV-2 infection, while 3.9% of them might have it at the time of the survey. Female sex (OR=1.334 [1.029-1.728]; p=0.030), obesity status (OR=1.961 [1.304-2.949]; p=0.001), asthma (OR=2.035 [1.433-2.890]; p=0.0001), autoim-mune diseases (OR=2.103 [1.381-3.201]; p=0.001), were all risk factors for showing mild SARS-CoV-2 infection. Instead, the elderly had a low probability to develop mild forms of the disease (OR=0.984 [0.975-0.994]; p=0.001). CONCLUSION: A remarkable number of subjects in Southern Tuscany may have already had a mild SARS-CoV-2 infection. Symptoms scores might be used to screen subjects with a suspected infection. Female sex, obesity, asthma, autoimmune diseases may be factors linked with mild forms of COVID-19 disease.

Hypercalciuria: its value as a predictive risk factor for nephrolithiasis in asymptomatic primary hyperparathyroidism?

CONTEXT: The latest guidelines of the 4th International Workshop on Asymptomatic Primary Hyperparathyroidism (aPHPT) reintroduced hypercalciuria (i.e. urinary calcium > 400 mg/day) as criterion for surgery. However, the value of hypercalciuria as a predictor of nephrolithiasis and the correct cut-off values still need to be confirmed. OBJECTIVE: To evaluate the prevalence of silent kidney stones in a large series of patients with aPHPT and the sensibility, specificity and predictive value of different cut-off values of hypercalciuria in identifying patients with nephrolithiasis. DESIGN: One hundred seventy-six consecutive patients with aPHPT were evaluated at our Institution by serum and urinary parameters and kidney ultrasound. RESULTS: Silent nephrolithiasis was found in 38 (21.6%) patients. In the univariate and multivariate model, hypercalciuria was a predictor of nephrolithiasis using the criterion of 400 mg/24 h [(OR 2.30, (1.11-4.82) P = 0.025], 4 mg/kg/bw [OR 2.65, (1.14-6.25) P = 0.023], gender criterion [OR 2.79, (1.15-6.79) P = 0.023] and the cut-off value derived from the ROC analysis [(> 231 mg/24 h) OR 5.02 (1.68-14.97) P = 0.004]. Despite these several predictive criteria, however, hypercalciuria had a low positive predictive value (PPV), ranging from 27.4 to 32.7%. CONCLUSIONS: Hypercalciuria is a predictor of nephrolithiasis, but its PPV is low.

Should omalizumab be used in severe asthma/COPD overlap?

A large number of patients suffering from asthma or chronic obstructive pulmonary disease (COPD) can show overlapping features of both diseases. Several subjects affected by asthma-COPD overlap (ACO) may be at a severe stage, poorly responsive to triple therapy including inhaled corticosteroids, long-acting ß2 agonists and muscarinic antagonists. This review tries to explore whether omalizumab can be used in poorly controlled severe ACO patients. According to the few studies available, omalizumab may improve asthma outcomes in ACO, although the magnitude of improvements may be lower in comparison to those obtained in subjects affected only by severe asthma. Omalizumab, by acting on IgE, might improve the eosinophilic pattern which is characteristic of the ACO asthma inflammation component. It can be hypothesized that a prevalence of Th1/Th17 airway inflammation pathways can modulate a lower response to anti-IgE while a Th2 pattern can lead to a higher effectiveness to omalizumab in ACO. High levels of IgE, FeNO and blood eosinophil count may be markers of a better response to omalizumab. In conclusion, on the basis of the few studies available, omalizumab could be effective in poorly-controlled severe ACO, although to a reduced extent in comparison to patients affected only by asthma.

Clinical presentation and management of patients with primary hyperparathyroidism in Italy.

PURPOSE: Evaluation of the phenotype of primary hyperparathyroidism (PHPT), adherence to International Guidelines for parathyroidectomy (PTx), and rate of surgical cure. METHOD: From January 2014-January 2016, we performed a prospective, multicenter study in patients with newly diagnosed PHPT. Biochemical and instrumental data were collected at baseline and during 1-year follow-up. RESULTS: Over the first year we enrolled 604 patients (age 61 ± 14 years), mostly women (83%), referred for further evaluation and treatment advice. Five hundred sixty-six patients had sporadic PHPT (93.7%, age 63 ± 13  years), the remaining 38 (6.3%, age 41 ± 17  years) had familial PHPT. The majority of patients (59%) were asymptomatic. Surgery was advised in 281 (46.5%). Follow-up data were available in 345 patients. Eighty-seven of 158 (55.1%) symptomatic patients underwent PTx. Sixty-five (53.7%) of 121 asymptomatic patients with at least one criterion for surgery underwent PTx and 56 (46.3%) were followed without surgery. Negative parathyroid imaging studies predicted a conservative approach [symptomatic PHPT: OR 18.0 (95% CI 4.2-81.0) P < 0.001; asymptomatic PHPT: OR 10.8, (95% CI 3.1-37.15) P < 0.001). PTx was also performed in 16 of 66 (25.7%) asymptomatic patients without surgical criteria. Young age, serum calcium concentration, 24 h urinary calcium, positive parathyroid imaging (either ultrasound or MIBI scan positive in 75% vs. 16.7%, P = 0.001) were predictors of parathyroid surgery. Almost all (94%) of patients were cured by PTx. CONCLUSIONS: Italian endocrinologists do not follow guidelines for the management of PHPT. Negative parathyroid imaging studies are strong predictors of a non-surgical approach. PTx is successful in almost all patients.

Cypress pollen: an unexpected major sensitizing agent in different regions of Italy.

OBJECTIVES: In this multicenter survey, we assessed the impact of sensitization to cypress in atopic patients in Italy and determined whether cypress pollen concentration changed over time. METHODS: Allergists were required to collect the results of 100-200 consecutive skin prick tests (SPTs) performed during 2012. Seasonal symptoms were also recorded, as were airborne cypress pollen concentrations (data from the Italian Aerobiology Association) in 1998-2000 and 2010-2012. RESULTS: We examined 2258 atopic outpatients (56% females; age, 2-84 years) sensitized to at least 1 of the aeroallergens tested (Dermatophagoides species, grass, pellitory, olive, cypress, birch, Alternaria tenuis, and dog and cat dander). We found that 62.9%, 16.1%, and 32.7% of patients living in central, northern, and southern Italy, respectively, were sensitized to cypress (P < .0001). The cypress pollen concentration peak was delayed from February to March in 1998-2000 and 2010-2012 in all 3 regions, with a shift in pollination towards spring. Patients who were monosensitized to cypress reported mainly rhinitis (90.7%-97.6%) and conjunctivitis (38.1%-100%). In polysensitized patients, the prevalence of rhinitis, conjunctivitis, and asthma increased progressively (P < .0001) from southern to northern Italy. The same trend was observed for the prevalence of reported winter symptoms typical of cypress allergy (28%-65%). CONCLUSIONS: Today, cypress pollen is the most frequent sensitizing aeroallergen (assessed by SPT) in several areas of central Italy. Variations in the timing of the cypress pollination period may have favored this increased sensitization. Rhinitis and conjunctivitis are the predominant symptoms. The clinical impact of this allergy was poor in southern Italy and increased in central areas before reaching its peak in northern regions.

Influence of allergic status and nasal polyposis on long-term Benralizumab response in eosinophilic severe asthma.

Objective: It is unclear whether Benralizumab effectiveness in severe eosinophilic asthma can be influenced by nasal polyposis (NP) or allergic status associations. We evaluated whether Benralizumab long-term efficacy in asthma outcomes could be different in subjects with atopy (SAEA) compared to the effectiveness in those without allergies (SNAEA) and in individuals with NP compared to those without NP. Methods: This observational retrospective study considered 95 consecutive patients divided into allergic (SAEA; n:65[68.4%]; skin prick tests positive [SPT] and/or IgE values ≥100 UI/mL), and non-allergic (SNAEA; n:30[31.6%], SPT negative and normal IgE levels<100 UI/mL). Overall population was also divided into two groups according to NP presence (NP+:39[41%] and NP-:56[59%]). Benralizumab treatment mean was19.7±7.2 months (range 12-35). Results: No differences in Benralizumab effectiveness were found in asthma outcomes in patients with/without NP. SNOT-22 improvement was higher in NP+ (-22±24) compared to NP- groups (6.33±15.5;p=0.055). FEV1 (16.33±19.22%), ACT(7.45±3.95) increases and frequency of SABA use (3.37±4.99) reduction were higher in SAEA compared to what obtained in non-allergic subjects (FEV1:8.15±15.6%,p=0.043; ACT:4.89±3.57,p=0.005; SABA use:-1.16±1.84;p=0.015). 93.8% of SAEA patients whereas only 72.2% of SNAEA individuals reduced OC doses at least half after Benralizumab (p=0.035). These results were partially confirmed by linear regression models showing associations between allergic status and FEV1, ACT and SABA use changes (ß=8.37;p=0.048, ß=2.056;p=0.033 and ß=-2.184;p=0.042 respectively). Conclusion: Benralizumab effectiveness in asthma appears to be independent of NP presence. The allergic eosinophilic disease, compared to just eosinophilic asthma, may be a more severe phenotype. Benralizumab may have greater efficacy in SAEA on some outcomes.

Severe asthma and long-term Benralizumab effectiveness in real-life.

OBJECTIVE: Long-term efficacy of Benralizumab in real life is not clearly known. We assessed the long-term effectiveness persistence to anti-IL-5R treatment in a group of severe eosinophilic asthmatics. PATIENTS AND METHODS: We retrospectively analyzed 95 individuals affected by severe asthma (36 males  ̶ 37.9%; mean age 58.1 ± 12.2) treated with Benralizumab (mean time 19.7 ± 7.2 months, range 12-35). Outcomes were evaluated at the beginning and at the end of patients' treatment periods. RESULTS: Mean baseline blood eosinophils were 897.5 ± 720.1 cells/µL (11 ± 5.6%) decreasing to 7.4 ± 20.6 cells/µL (0.97 ± 0.26%; p < 0.0001) after Benralizumab. FENO likewise decreased from 63.9 ± 68.4 to 28.4 ± 23.6 ppb, while FEV1% significantly improved (p < 0.0001). Mean FEF25-75 also increased from 45.8 ± 24.6% to 60.7 ± 24.6%, whereas RAW dropped from 202.15 ± 109.6% to 135.2 ± 54.75% (p < 0.0001). Also, lung volumes greatly decreased. ACT/ACQ significantly improved, while exacerbations number fell from 4.1 ± 2.4, before anti-IL-5R, to 0.33 ± 0.77, after treatment (p < 0.0001). Rhinitis severity levels and SNOT-22 also changed favorably. Patients that took long-term OCs were 71.6% before treatment, decreasing to 23.2% after Benralizumab (p < 0.0001), with an OCs dose reduction from 14.8 ± 8.9 to 1.45 ± 2.8 mg/day (p < 0.0001). 51.6% of subjects used SABA as needed before Benralizumab, falling to 4.2% after treatment. Several patients showed a reduction of ICS doses, SABA use and maintenance therapy step-down. Clinical/biological response with anti-IL-5R remained constant or even improved in terms of exacerbations or maintenance therapy reductions over time. On the contrary, FEF25-75% improvement slowed down in the long-term. No relationship was found between baseline blood eosinophil number and therapeutic response. CONCLUSIONS: Long-term Benralizumab effectiveness persistence in all outcomes in real life was confirmed.

Thyroid hormone, amiodarone therapy, and prognosis in left ventricular systolic dysfunction.

BACKGROUND: Amiodarone protects patients with left ventricular systolic dysfunction (LVSD) against serious arrhythmias, but it also has numerous side effects on non-cardiac organs, such as the thyroid. Indeed, amiodarone may inhibit the peripheral conversion of T4 into T3. Pathologically reduced serum levels of T3 - the so-called "low T3 syndrome" (LOWT3) - increase mortality in patients with LVSD and not on amiodarone. AIM: The aim of the study was to examine the relationship between thyroid hormone status, amiodarone therapy, and outcome in a population with LVSD. MATERIAL/ SUBJECTS AND METHODS: A total of 2344 patients with LVSD and free of overt hyper- and hypothyroidism were enrolled. The population was divided into 4 groups: group 1 (LOWT3 and amiodarone therapy, no.=126), group 2 (isolated amiodarone therapy, no.=74), group 3 (isolated LOWT3, no.=682), group 4 (controls, no.=1462). RESULTS: Kaplan-Meier curves showed, after a mean follow-up of 31 months, increased total and cardiac mortality in groups 1 (30% and 20%, respectively), 2 (23%, 11%), and 3 (22%, 12%) compared to group 4 (total mortality log-rank 82.8, p<0.0001; cardiac mortality log-rank 63.1, p<0.0001). At Cox analysis, adjusted for several clinical variables, survival was reduced in groups 1 and 3 compared to group 4. Group 2 had a similar mortality to group 4, although the number of patients was too limited to accurately assess the effect of amiodarone on long-term prognosis. CONCLUSIONS: LOWT3 exerts an adverse impact on prognosis in LVSD, which is not influenced by concomitant amiodarone therapy.

A regular or an intermittent treatment for asthma: the long-term effect.

OBJECTIVES: Many asthmatics take therapy intermittently because of their scarce compliance. It is not known if this is effective in controlling and slowing down the lung function decline in asthma. Our aim was to compare the effect of a regular treatment and an intermittent one on some clinical aspects and on the forced expiratory volume 1 (FEV1) decline in 165 persistent asthmatics with FEV1 > 70% (60 men; age 40.87 +/- 14.05; FEV1 95.03 +/- 13.1%), in a retrospective way over 4 years. PATIENTS AND METHODS: Eighty-four patients took inhaled corticosteroids (ICSs) plus long-acting bronchodilator agents (LABAs) regularly (regular) and 81 patients took ICSs plus LABAs intermittently for short periods when symptoms appeared (intermittent). RESULTS: Less patients (p < 0.05) took oral corticosteroids, short-acting bronchodilators as needed in regular compared to intermittent. More patients increased the therapy (step-up) in intermittent (p < 0.01) More patients reported a subjective improvement while fewer reported a worsening in regular (p < 0.05). After 4 years, the variation in maximal mid expiratory flow (FEF25-75) was lower in regular (-159.40 +/- 472.79 ml/sec; CI 95% -261.99, 56.82) than in intermittent (-324.44 +/- 569.97 ml/sec; CI 95% -450.48, -198.41); whereas the FEV1 decline was similar between regular (-276.97 +/- 199.37 ml; CI 95% -316.24, -229.71) and Intermittent (-317.65 +/- 194.05 ml; CI 95% -360.56, -274.74). In males and females, in smokers and non-smokers no differences were found in the FEV1 decline. CONCLUSIONS: In conclusion, the regular use of ICSs plus LABAs is better than the irregular use of them in controlling asthma over a long period of time. Whereas, after 4 years the regular treatment may not decrease the FEV1 decline more effectively than the intermittent therapy.

Normal Values of the Mitral-Aortic Intervalvular Fibrosa Thickness: A Multimodality Study.

BACKGROUND: The avascular region of the fibrous body between the mitral and aortic valves, named mitral-aortic intervalvular fibrosa (MAIVF), is often involved in the periaortic diffusion of infective endocarditis (IE), resulting in abscess or pseudoaneurysm formation. The early recognition of these life-threatening complications is of crucial importance, as urgent surgical correction is necessary. In the first stages of the abscess formation, the only sign is an increased thickness of the MAIVF. To the best of our knowledge, normal transesophageal echocardiography (TEE) examination reference values for MAIVF thickness has not yet been established. The aim of the study was to define the normal ranges of MAIVF thickness in a population of healthy adults who underwent a TEE examination. MATERIALS AND METHODS: A population of consecutive adult patients who underwent a TEE examination was enrolled in the study. Measurement was performed in short-axis (SAX) and long-axis (LAX) views. Mean-2 standard deviations (mean-2SDs) and 5%, 10%, 90%, and 95% confidence intervals were evaluated. A comparison with MAIVF thickness in patients affected by aortic IE complicated by abscess formation was performed, and receiver operating characteristic (ROC) curves were constructed to achieve the optimal cutoff value of normality. RESULTS: A total of 477 consecutive Caucasian adult patients were enrolled (mean age: 69 years, range: 27-93 years). Mean-2SD MAIVF measurement in SAX view was 0.325 cm (95% confidence interval [CI]: 0.319-0.330 cm) and in LAX view was 0.340 cm (95% CI: 0.334-0.346 cm). Computed tomography-MAIVF mean measurement (±2SD) was 0.237 cm (95% CI: 0.110-0.340 cm). ROC curves showed that a cutoff SAX value measurement of 0.552 (area under the curve [AUC]: 95.2%) had a sensibility of 88.2% and a specificity of 92.4%; a LAX measurement value of 0.623 (AUC: 93.3%) had a sensibility of 82.7% and a specificity of 85.7%. The multivariate analysis showed no significant correlation between MAIVF thickness, age, and sex. CONCLUSION: In healthy patients, MAIVF thickness should not exceed 0.600 cm. Above these values, the suspicion of a periaortic abscess formation should be raised. MAIVF increased thickness may be an early sign of perivalvular diffusion requiring an urgent endocarditis team evaluation.

Factors reducing omalizumab response in severe asthma.

BACKGROUND: Despite adding Omalizumab to conventional therapy, several severe asthmatics still show poor disease control. We investigated the factors that may affect a reduced Omalizumab response in a large population of severe asthmatics. METHODS: 340 patients were retrospectively evaluated. FEV1%, FVC%, Asthma Control Test (ACT), fractional exhaled nitric oxide (FENO), possible step-downs/step-ups of concomitant therapies, exacerbations, disease control levels, ICS doses and SABA use, observed at the end of treatment, were considered as a response to Omalizumab. RESULTS: Age was an independent risk factor for a reduced response concerning FEV1%, FVC%, ACT and for a lower asthma control. Obesity (vs normal weight) was a determinant condition for exacerbations (OR:3.114[1.509-6.424], p = 0.002), for a disease partial/no control (OR:2.665[1.064-6.680], p = 0.036), for excessive SABA use (OR:4.448[1.837-10.768], p = 0.002) and for an unchanged/increased level of concomitant asthma medications. Furthermore, obesity also reduced the response in FEV1 (ß = -6.981,p = 0.04), FVC (ß = -11.689,p = 0.014) and ACT (ß = -2.585, p = 0.027) and was associated with a higher FENO level (ß = 49.045,p = 0.040). Having at least one comorbidity was a risk factor for exacerbations (OR:1.383[1.128-1.697], p = 0.008) and for an ACT <20 (OR:2.410[1.071-3.690], p = 0.008). Specifically, chronic heart disease was associated with both a lower ACT and FVC% whereas gastroesophageal reflux with a partial/no asthma control. Nasal polyps were a predisposing factor leading both to exacerbations and to the use of higher inhaled corticosteroids doses. Moreover, smoking habits, pollen or dog/cat dander co-sensitizations may negatively influence Omalizumab response. CONCLUSION: Age, obesity, comorbidities, smoking habits, nasal polyps, allergic poly-sensitization might reduce Omalizumab effectiveness independently to other asthma-influencing factors.

Could a vitamin D deficiency cause a combined long-term FEV1 and bone mineral density deterioration in female asthmatics?

OBJECTIVES: We already know that asthma is associated to osteoporosis/osteopenia and characterized by an accelerated lung function decline. Our study aimed at assessing whether lung function decline and bone mineral density (BMD) deterioration in time were associated in a group of female long-standing asthmatics. We also tried to understand whether these two aspects were related to ICS treatment and vitamin D levels. METHODS: 35 female asthmatics were retrospectively analysed. Results of methacholine challenge test at asthma onset, FEV1%, bone density scan at moment of recruitment and after at least 5years later were considered. RESULTS: A significant positive relationship between femoral-t-scores changes and FEV1 decline was found after a median follow-up time of 7 [6-9] years (r=0.43;p=0.04). Femoral-t-score variations and vitamin D values were also significantly related (r=0.669;p=0.024). Furthermore, we found that FEV1 decline was worse in subjects with lower vitamin D levels (-57.5[-80.4-35.9]ml/year), compared to those with normal vitamin D rates (12[-16-23.6]ml/year;p=0.055). Femoral/vertebral t-score changes, as well as FEV1, decline were not associated to the use of medium/high ICS doses when compared to subjects treated with low ICS dosages. CONCLUSIONS: FEV ¹ decline and BMD deterioration in time observed in a group of female asthmatics were associated; low vitamin D levels may be the link.

Effects of omalizumab in severe asthmatics across ages: A real life Italian experience.

BACKGROUND: This retrospective study aimed at evaluating long-term effects of Omalizumab in elderly asthmatics in a real-life setting. METHODS: 105 consecutive severe asthmatics (GINA step 4-5; mean FEV1% predicted:66 ± 15.7) treated with Omalizumab for at least 1 year (treatment mean duration 35.1 ± 21.7 months) were divided into 3 groups according to their age at Omalizumab treatment onset: 18-39, 40-64 and ≥ 65 years. RESULTS: Comorbidities, number of overweight/obese subjects and patients with late-onset asthma were more frequent among older people. A similar reduction of inhaled corticosteroids dosage and SABA on-demand therapy was observed in all groups during Omalizumab treatment; a similar FEV1 increased was also observed. Asthma Control Test (ACT) improved significantly (p < 0.001) in the three groups, increasing from 15 [IQR:12-18] to 24 [IQR:22-25] in younger subjects, from 14 [IQR:10-16] to 21 [IQR:20-23] in the 40-64-year-group and from 15 [IQR:12-16] to 20 [IQR:18-22] in elderly patients where improvement was lower (p = 0.039) compared to younger people. Asthma exacerbations decreased significantly after Omalizumab but the percentage of exacerbation-free patients was higher in younger people (76.9%) compared to middle aged patients (49.2%) and the elderly (29%) (p = 0.049). After Omalizumab treatment, the risk for exacerbations was lower in subjects aged 40-64 (OR = 0.284 [CI95% = 0.098-0.826], p = 0.021) and 18-39 (OR = 0.133 [CI95% = 0.026-0.678], p = 0.015), compared to elderly asthmatics. Also, a significantly reduced ACT improvement (ß = -1.070; p = 0.046) passing from each age class was observed. CONCLUSION: Omalizumab improves all asthma outcomes independently of age, although the magnitude of the effects observed in the elderly seems to be lower than in the other age groups.

Can we modulate asthma maintenance treatment level with disease seasonal variations?

Asthma can have clinical seasonal fluctuations due to different exposure factors. The analysis of our data and literature confirm a seasonal trend of asthma severity. In this brief review, authors discuss the possibility to adapt maintenance therapy level to clinical seasonal fluctuations, by increasing treatment in some seasons to prevent exacerbations and by decreasing it in others, when symptoms are low, in order to minimize costs and maximize safety. Literature and our data (concerning studies carried out in areas with a temperate climate) indicate that asthma severity is reduced in summer while it tends to increase in the other seasons. Authors conclude that a preventive increasing maintenance treatment level during the season when we know that patients worsen (starting some weeks before symptom worsening) may reduce asthma exacerbation risks. On the contrary, a summer treatment reduction, in patients that improve during this period, may be considered only in asthma phenotypes with a benign disease course in time.

Flavonoids as antioxidant agents: importance of their interaction with biomembranes.

Flavonoids, a group of phenolic compounds widely occurring in the plant kingdom, have been reported to possess strong antioxidant activity. In the present study, four flavonoids (quercetin, hesperetin, naringenin, rutin), chosen according to their structural characteristics, were tested in two different in vitro experimental models: (1) Fe(2+)-induced linoleate peroxidation (Fe(2+)-ILP), by detection of conjugated dienes; and (2) autooxidation of rat cerebral membranes (ARCM), by using thiobarbituric acid for assay of free malondialdehyde production. The results obtained were also interpreted in the light of flavonoid interactions, studied by differential scanning calorimetry, with dipalmitoylphosphatidylcholine (DPPC) vesicles as a biological membrane model. The antilipoperoxidant activity of the flavonoids tested can be classified as follows: rutin > hesperetin > quercetin > naringenin in the Fe(2+)-ILP test: quercetin > rutin > hesperetin > naringenin in the ARCM test. Quercetin, hesperetin, and naringenin interacted with DPPC liposomes causing different shifts, toward lower values, of the main transition peak temperature (Tm) typical for DPPC liposomes; however, no change in Tm of DPPC dispersion was observed in the presence of rutin. The hypothesis will be discussed that flavonoid capacity to modify membrane-dependent processes, such as free-radical-induced membrane lipoperoxidation, is related not only to their structural characteristics but also to their ability to interact with and penetrate the lipid bilayers.

Genetically epilepsy-prone rodents show some changes of ion levels in the brain.

In the present study the water and ion (Na+, K+, Ca2+, Fe3+, Se4+, Mg2+, Mn2+, Mn2, Se4+, Cu2+) content in the brain of genetically epilepsy-prone rats (GEPRs) and of 21-, 45-, and 60-day-old DBA/2 mice were determined, and compared with those measured in normal controls (Sprague-Dawley rats and Swiss mice), to verify whether the predisposition to audiogenic seizures (AGS) may be partially related to changes in the cerebral osmotic and ionic state. Our findings clearly evidenziate two points: a) a more complex shift in brain ionic balance (rather than a peculiar modification in the concentration of a single ion) seems very likely involved in AGS susceptibility; (b) brain Ca2+ and Se4+ amounts, together with the water content, appear to be really important factors to which a role in abnormal seizure predisposition may be attributed.

Systemic cytokine administration can affect blood-brain barrier permeability in the rat.

The aim of the present study was to clarify the effect of intracarotid injection of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) on the permeability of the blood-brain barrier (BBB) in the rat. A regional blood-to-brain transfer constant (Ki) for [14C] alpha-aminoisobutyric acid ([14C]AIB) and the cerebral residual blood volume were calculated 10 min following administration of cytokines (CKs; 1000 U/rat). The injection of IL-2 and IL-6 (but not of IL-1 beta) induced a significant enhancement of Ki values for [14C]AIB within several brain areas; conversely, when the rats were given TNF-alpha, a striking decrease in BBB permeability was observed. The cerebral regional blood volumes appeared significantly lower in the rats injected with IL-6 than in the control animals, but markedly increased following TNF-alpha administration. Our findings confirm the ability of some CKs to affect the permeability of the BBB and/or to act, probably indirectly, as vasomodulator agents of the cerebral microvessel endothelium.