Exploring Orthogonality between Halogen and Hydrogen Bonding Involving Benzene.

The concept of orthogonality between halogen and hydrogen bonding, brought out by Ho and coworkers some years ago, has become a widely accepted idea within the chemists' community. While the original work was based on a common carbonyl oxygen as acceptor for both interactions, we explore here, by means of M06-2X, M11, ωB97X, and ωB97XD/aug-cc-PVTZ DFT calculations, the interdependence of halogen and hydrogen bonding with a shared π-electron system of benzene. The donor groups (specifically NCBr and H2O) were placed on either or the same side of the ring, according to a double T-shaped or a perpendicular geometry, respectively. The results demonstrate that the two interactions with benzene are not strictly independent on each other, therefore outlining that the orthogonality between halogen and hydrogen bonding, intended as energetical independence between the two interactions, should be carefully evaluated according to the specific acceptor group.

Randomised clinical trial in women with Recurrent Vulvovaginal Candidiasis: Efficacy of probiotics and lactoferrin as maintenance treatment.

BACKGROUND: Vulvovaginal candidiasis (VVC) is a recurrent vaginal condition in childbearing women. OBJECTIVES: The aim of this study was to assess the efficacy of an oral formulation containing Lactobacillus acidophilus GLA-14, Lactobacillus rhamnosus HN001 and bovine lactoferrin on symptoms and recurrence of VVC as adjuvant therapy to topical clotrimazole. PATIENTS/METHODS: Forty-eight women positive for C. albicans, symptoms of VVC and documented history of recurrences were randomised into 2 groups receiving verum or placebo (2 capsules/day for 5 days followed by 1 capsule/day for additional 10 days) as adjuvant treatment to clotrimazole (induction phase) followed by a maintenance cycle of 6 months (1 capsule/day verum or placebo for 10 consecutive days each month). Symptoms, overall cure rate and recurrence rate were assessed. RESULTS: After clotrimazole therapy, a significant improvement of symptoms was shown in both groups. However, only women treated with probiotics and lactoferrin showed a significant improvement of itching and discharge at 3 and 6 months. During the six-month follow-up, recurrences were significantly less in the intervention group vs placebo (33.3% vs 91.7% after 3 months and 29.2% vs 100% after 6 months). CONCLUSIONS: The results show that the investigated lactobacilli mixture in combination with lactoferrin represents a safe and effective adjuvant approach for reducing symptoms and recurrences of RVVC.

Toxicity of Crepis lacera in grazing ruminants.

BACKGROUND: Crepis lacera is a plant from the Asteraceae family that is common in the Mediterranean region. Farmers believe that this plant may be deadly to small ruminants in areas of southern Italy. However, scientific evidence is lacking, and no proof exists that C. lacera is toxic to ruminants. Necropsies conducted on four sheep revealed lesions in their livers and kidneys. RESULTS: In the current study, we described sheep poisoning and isolated secondary metabolites from Crepis lacera to assess the metabolites' biological activity both in vitro and in vivo. Phytochemical study of the aerial portions of Crepis lacera led to the isolation of five sesquiterpene lactones and two phenolic compounds. Cellular viability was evaluated in cell cultures of the bovine kidney cell line Madin Darby Bovine Kidney (MDBK) after incubation with phytochemicals. Our results showed that three sesquiterpene lactones, 8-epidesacylcynaropicrin-3-O-ß-glucopyranoside (2), 8-epigrosheimin (3), and 8-ß-hydroxydehydrozaluzanin C (4), were cytotoxic after 48 h of incubation. In addition, in the in vivo study, animals that received 1 mg/kg body weight (bw) of Crepis lacera extract and were then sacrificed after 48 h showed significant lesions in their liver, lungs and kidneys. These lesions were also found in rats that received 2 mg/kg bw of the same extract and sacrificed after 24 and 48 h. CONCLUSIONS: These results validate the hypothesis that C. lacera is potentially dangerous when ingested in large quantities by grazing small domestic ruminants. Further studies are necessary to clarify the molecular mechanisms of Crepis spp. toxicity in animals.

Study on the effects of an oral lactobacilli and lactoferrin complex in women with intermediate vaginal microbiota.

PURPOSE: In the vagina of healthy reproductive-aged women, several microbial species maintain a finely tuned mutualistic relationship with the host providing the first-line of defense against the colonization by opportunistic pathogens, which are the leading cause of dysbiosis or vaginal infections (bacterial vaginosis, vulvovaginal candidiasis, and aerobic vaginitis). The use of probiotic lactobacilli to prevent vaginal infections has a good rationale, and an excellent safety record, but so far only a few strains have been clinically proven to be effective, particularly to prevent BV. The aim of the clinical trial was to evaluate the changes in Nugent score in women with intermediate vaginal microbiota treated with oral Lactobacillus acidophilus GLA-14 and Lactobacillus rhamnosus HN001 mixture, in combination with bovine lactoferrin RCX™ (Respecta®) or placebo, for 15 days. METHODS: Vaginal swabs were collected from each woman at baseline and at the end of probiotic treatment and analyzed by RT-PCR. Both symptoms of abnormal vaginal micorbiota and adverse effects were assessed throughout the study. RESULTS: The results showed that oral intake of lactobacilli/lactoferrin mixture led to significant vaginal colonization by L. acidophilus GLA-14 and L. rhamnosus HN001 showing that both strains can colonize vagina following oral ingestion. The effect of such colonization is correlated with the restoration of normal Nugent score (values 0-3) and an improvement of symptoms of abnormal vaginal micorbiota including itching and discharge. CONCLUSIONS: Oral consumption of lactobacilli/lactoferrin complex corroborates the effectiveness of using lactobacilli for supporting vaginal health and provides a rational basis for future studies on vaginal infections.

Astragalus membranaceus Extract Attenuates Inflammation and Oxidative Stress in Intestinal Epithelial Cells via NF-κB Activation and Nrf2 Response.

Astragalus membranaceus, dried root extract, also known as Astragali radix, is used in traditional Chinese medicine as a tonic remedy. Moreover, it has been reported that Astragalus membranaceus could attenuate intestinal inflammation; however, the underlying mechanism for its anti-inflammatory activity in intestinal epithelial cells (IECs) remains unclear. In this study, we evaluated Astragalus membranaceus extract (5-100 µg/mL) in a model of inflammation and oxidative stress for IECs. We showed that Astragalus membranaceus extract reduced the inflammatory response induced by lipopolysaccharide from E. coli (LPS) plus interferon-γ (IFN), decreasing tumor necrosis factor-α (TNF-α) release, cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, nitrotyrosine formation, nuclear factor-κB (NF-κB) activation, and reactive oxygen species (ROS) release in the non-tumorigenic intestinal epithelial cell line (IEC-6). The antioxidant potential of Astragalus membranaceus extract was also evaluated in a model of hydrogen peroxide (H2O2)-induced oxidative stress in IEC-6, indicating that this extract reduced ROS release and increased nuclear factor (erythroid-derived 2)-like 2 (Nrf2) activation and the expression of antioxidant cytoprotective factors in these cells. The results contributed to clarify the mechanisms involved in Astragalus membranaceus extract-reduced inflammation and highlighted the potential use of this extract as an anti-inflammatory and antioxidant remedy for intestinal diseases.

Comparative Bioavailability of Two Diosmin Formulations after Oral Administration to Healthy Volunteers.

Diosmin is a flavonoid commonly found in citrus fruits, largely used as adjuvant treatment for circulatory disorders, including chronic venous insufficiency (CVI) and hemorrhoids. Following oral administration, diosmin is not directly absorbed but must first be hydrolyzed into its aglycone, diosmetin, which is then absorbed into the systemic circulation. The aim of the current cross-over clinical study was to assess the pharmacokinetic profile of µSmin® Plus, a micronized diosmin flavonoid complex standardized in diosmin and formulated with a buffering agent (tested formulation). The study compared this to unformulated micronized diosmin (reference), in 16 healthy volunteers. Plasma samples were analyzed by HPLC-MS and plasma diosmetin concentration was measured after deconjugation with ß-glucuronidase. For the tested formulation area under the curve (AUC0-t), and maximum plasma and time concentration (Cmax; tmax) were found to be 298.4 ± 163.7, 50.3 ± 22.6 and 2.2 ± 2.9, respectively. AUC0-t and Cmax of the reference were 31.9 ± 100.4 and 2.4 ± 1.9, respectively. The tested formulation showed higher plasmatic concentrations of diosmetin in comparison to those obtained after the administration of unformulated micronized diosmin. The relative bioavailability was 9.4 greater for the tested formulation than in micronized diosmin. In conclusion, our data indicate that µSmin® Plus was rapidly and well absorbed into systemic circulation and may therefore be ideally suitable to deliver diosmin in human interventional trials.

Severe Spontaneous Echo Contrast/Auricolar Thrombosis in "Nonvalvular" AF: Value of Thromboembolic Risk Scores.

BACKGROUND: Patients with atrial fibrillation (AF) have an increased thromboembolic risk that can be estimated with risk scores and sometimes require oral anticoagulation therapy (OAT). Despite correct anticoagulation, some patients still develop left atrial spontaneous echo contrast (SEC) or thrombosis. The value of traditional risk scores (R2 CHADS2 , CHADS2 , and CHA2 DS2 -VASc) in predicting such events remains controversial. METHODS AND RESULTS: The aim of our study was to explore variables linked to severe SEC or atrial thrombosis and evaluate the performance of traditional risk scores in identifying these patients. In order to do this, we retrospectively analyzed 568 patients with nonvalvular nonparoxysmal AF who underwent electrical cardioversion from January 2011 to December 2016 after OAT for a minimum of 4 weeks. A transesophageal echocardiogram was performed in 265 patients for various indications, and 24 exhibited left atrial SEC or thrombosis. Female gender, history of heart failure or left ventricular ejection fraction <40%, and high levels (>1 mg/dL) of C-reactive protein (CRP) were independently associated with left atrial SEC/thrombosis. A score composed by these factors (denominated HIS [Heart Failure, Inflammation, and female Sex]) showed a sensitivity of 79% and a specificity of 60% (area under receiver operating characteristic curve 0.695, P = 0.002) in identifying patients with a positive transesophageal echo; traditional risk scores did not perform as well. CONCLUSIONS: In patients with persistent AF and suboptimal anticoagulation, a risk score composed by history of heart failure, high CRP, and female gender identifies patients at high risk of left atrial SEC/thrombosis when its value is >1.

The electronic circular dichroism of nicotine in aqueous solution: a test case for continuum and mixed explicit-continuum solvation approaches.

In this paper, we extend an integrated QM/MM/polarizable continuum model (PCM) method, which combines a fluctuating charge (FQ) approach to the MM polarization with the PCM, to describe electronic circular dichroism (ECD) spectra of systems in aqueous solution. The main features of the approach are presented, and then applications to the UV and ECD spectra of neutral (S)-nicotine in aqueous solution are reported. The performance of the QM/FQ/PCM is compared with that of the PCM against newly measured UV ECD spectra, which are in agreement with previous findings. The inclusion of specific solvation effects via the QM/FQ/PCM method leads to an improvement in the calculated spectra compared to the experimental findings, though the pure PCM results are still qualitatively correct and are a useful tool for the characterization of the states.

Lactobacilli vaginal colonisation after oral consumption of Respecta(®) complex: a randomised controlled pilot study.

PURPOSE: The aim of the current pilot study was to determine if oral consumption of a combination of two probiotics; L. acidophilus La-14, L. rhamnosus HN001, and bovine lactoferrin (Respecta(®) complex), would lead to the detection with molecular techniques of the consumed probiotic strains in the vagina. METHODS: Healthy volunteers (40) consumed the study product twice daily for 2 weeks. Vaginal swabs were collected at 0, 1, 2 and 3 weeks and analysed for the consumed organisms by qPCR. RESULTS: Vaginal L. rhamnosus and L. acidophilus levels were significantly increased on days 14 and 21. On days 14 and 21 a significant number of women had increased levels of vaginal L. acidophilus and on days 7 and 21 a significant number of women had increased levels of vaginal L. rhamnosus. CONCLUSIONS: Consumption of L. acidophilus La-14, L. rhamnosus HN001 in combination with bovine lactoferrin leads to vaginal detection; even 1 week after consumption was stopped. This provides a basis for future studies on urogenital tract health.

Five-year retrospective Italian multicenter study of visceral leishmaniasis treatment.

The treatment of visceral leishmaniasis (VL) is poorly standardized in Italy in spite of the existing evidence. All consecutive patients with VL admitted at 15 Italian centers as inpatients or outpatients between January 2004 and December 2008 were retrospectively considered; outcome data at 1 year after treatment were obtained for all but 1 patient. Demographic characteristics, underlying diseases, diagnostic procedures, treatment regimens and outcomes, as well as side effects were recorded. A confirmed diagnosis of VL was reported for 166 patients: 120 (72.3%) immunocompetent, 21 (12.6%) patients with immune deficiencies other than HIV infection, and 25 (15.1%) coinfected with HIV. Liposomal amphotericin B (L-AmB) was the drug almost universally used for treatment, administered to 153 (92.2%) patients. Thirty-seven different regimens, including L-AmB were used. The mean doses were 29.4 ± 7.9 mg/kg in immunocompetent patients, 32.9 ± 8.6 mg/kg in patients with non-HIV-related immunodeficiencies, and 40.8 ± 6.7 mg/kg in HIV-infected patients (P < 0.001). The mean numbers of infusion days were 7.8 ± 3.1 in immunocompetent patients, 9.6 ± 3.9 in non-HIV-immunodeficient patients, and 12.0 ± 3.4 in HIV-infected patients (P < 0.001). Mild and reversible adverse events were observed in 12.2% of cases. Responsive patients were 154 (93.3%). Successes were 98.4% among immunocompetent patients, 90.5% among non-HIV-immunodeficient patients, and 72.0% among HIV-infected patients. Among predictors of primary response to treatment, HIV infection and age held independent associations in the final multivariate models, whereas the doses and duration of L-AmB treatment were not significantly associated. Longer treatments and higher doses of L-AmB were not able to significantly modify treatment outcomes either in the immunocompetent or in the immunocompromised population.

Bacillus coagulans LMG S-24828 Impairs Candida Virulence and Protects Vaginal Epithelial Cells against Candida Infection In Vitro.

Probiotics are living microbes that provide benefits to the host. The growing data on health promotion, following probiotics administration, increased interest among researchers and pharmaceutical companies. Infections of the lower genital tract in females, caused by a wide range of pathogens, represent one of the main areas for the use of probiotics and postbiotics. Vulvovaginal candidiasis (VVC) affects 75% of women of reproductive age at least once during their lifetime, with 5-8% developing the recurrent form (RVVC). The disease is triggered by the overgrowth of Candida on the vaginal mucosa. Here, in order to establish its probiotic potential in the context of VVC, we evaluated the anti-fungal effects of the spore-producing Bacillus coagulans LMG S-24828 against C. albicans and C. parapsilosis as well as its beneficial effects in counteracting Candida vaginal infection in vitro. Our results show that both live B. coagulans and its Cell-Free Supernatant (CFS) exerted antifungal activity against both fungi. Moreover, live B. coagulans reduced hyphal formation, inhibited C. albicans adhesion to vaginal epithelial cells, showed co-aggregation capacity, and exerted a protective effect on vaginal epithelial cells infected with C. albicans. These data suggest that B. coagulans LMG S-24828 may provide benefits in the context of Candida vaginal infections.

Alteration of Smell and Taste in Asymptomatic and Symptomatic COVID-19 Patients in Sicily, Italy.

OBJECTIVES: Alteration of smell and taste has been reported in patients with coronavirus disease 2019 (COVID-19). The incidence and clinical-symptomatic manifestation of COVID-19 is different between northern and southern Italy. This study aims to evaluate the onset of alteration of smell and taste in asymptomatic and symptomatic patients in Sicily (extreme south of Italy). METHODS: This prospective cross-sectional study was performed on asymptomatic and symptomatic COVID-19 patients tested for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) from May 1 to May 15, 2020. A questionnaire was used for evaluating the prevalence of smell and taste disorders in COVID-19 patients before performing nasopharyngeal swab. RESULTS: Of the total 292 patients, 242 (83.2%) were negative for SARS-CoV-2 and 50 were positive (16.8%). Twenty-six of the 50 (52%) SARS-CoV-2 positive patients reported smell/taste disorders. Twenty-eight of the 50 (57.1%) SARS-CoV-2 positive patients were hospitalized (group A), and 22 (42.9%) were nonhospitalized (group B). The mean age in group A and group B was 45.4 ± 13.7 years and 57.0 ± 15.0, respectively (P = .007). The symptoms reported by hospitalized patients were fever (71.4%), cough (64.2%), fatigue (82.1%), and dyspnea (100%), while in nonhospitalized patients, the most reported symptoms were sore throat (72.7%), rhinorrhea (77.2%), and altered smell (81.8%). Anosmia/hyposmia reported in group A and group B was 28.5% and 81.8%, respectively (P = .001). CONCLUSION: These preliminary results indicate that the majority of SARS-Cov-2 positive patients in southern Italy did not require hospitalization and presented with milder symptoms or no symptoms and the alterations in smell and taste occurred.

Effects of a nutraceutical combination of monacolin, γ-oryzanol and γ-aminobutyric acid on lipid profile and C-reactive protein in mice.

INTRODUCTION: The aim of this study was to evaluate the efficacy of two nutraceutical agents aimed to improve lipid profile in a sample of mice. MATERIAL AND METHODS: Fifty mice were randomly divided into four groups. Control mice were fed a standard diet (SD), while the other three groups were fed with a high-fat diet (HFD) for 4 weeks. At the end of the run-in period, mice fed with the SD continued to follow the SD, while mice fed with the HFD were divided into three groups: one continued with the HFD, one continued to follow the HFD + a blend of natural components derived from rice and fermented rice (monacolin K 3%, γ-oryzanol, and γ-aminobutyric acid) (S1), and the other one followed the HFD + one nutraceutical containing monacolin K 3% alone for 24 weeks. RESULTS: The results showed that mice treated with HFD + S1 and HFD + S2 had lower levels of TC compared to mice fed with the HFD alone (p < 0.01, and p < 0.05, respectively). Moreover, mice treated with HFD + S1 had lower TC and LDL-C levels compared to mice fed with HFD + S2 (p < 0.05). Mice treated with HFD + S1 or S2 had lower Tg levels compared to mice fed with the HFD (p < 0.05). CONCLUSIONS: We can conclude that a combination of monacolin K 3%, γ-oryzanol, and γ-aminobutyric acid is more effective than monacolin K 3% alone in reducing the negative effects of a HFD in a sample of specific pathogen-free mice.

[Association between raised IL-8 serum levels and resistance to combined peg-interferon plus ribavirin therapy in HCV+ active chronic hepatitis]. / associazione tra elevati livelli sierici di IL-8 e resisitenza alla terapia combinata con PEG-interferon + ribavirina nell'epatite cronica attiva HCV+.

IL-8 serum levels were measured in a group of 44 patients affected with Chronic Active Hepatitis (CAH) HCV+ at the beginning and end of peg-interferon plus ribavirin combined therapy. IL-8 levels were compared with those measured in a group of healthy controls. The patients were treated for 12 months, and then followed up for 6 months after the end of the therapy. IL-8 serum levels were detected by ELISA at the beginning and end of the therapy, and then at the end of the follow-up. IL-8 serum levels were significantly more elevated (p<0.01) in CAH HCV+ patients than in the healthy controls. Furthermore, IL-8 serum levels in those patients who subsequently showed a sustained virological response to the therapy, declined on treatment and maintained lower levels than in those who did not respond to therapy. Serum IL-8 can be considered and proposed as a non-invasive and predictive marker of response to combined PEG IFN alpha2b + Ribavirin in CAH HCV +.

Accumulation of Polychlorinated Biphenyls in Mussels: A Proteomic Study.

Polychlorinated biphenyls (PCBs) are environmental pollutants of industrial origin that can contaminate food, mainly food of animal origin. Although production of PCBs has been banned in many countries since the 1980s, they are still present in the environment and are considered dangerous pollutants for human health. In fact, they can bioaccumulate in living organisms such as marine organisms because of their chemical and physical properties. New analytical approaches are useful to monitor the presence of such contaminants in seafood products and in the environment. In this work, we evaluate changes in protein expression of Mytilus galloprovincialis (Lam.) experimentally exposed to a PCB mixture and identify chemically specific protein expression signatures by using a proteomic approach. In particular, we identify 21 proteins whose levels of expression are sensibly modified after 3 weeks of exposure. The present work shows that a proteomic approach can be a useful tool to study alterations of protein expression in mussels exposed to PCBs and represents a first step toward the development of screening protocols to be used for biomonitoring surveys of fishery products.

Effects of Lactobacillus rhamnosus and Lactobacillus acidophilus on bacterial vaginal pathogens.

The human vagina is colonized by a variety of microbes. Lactobacilli are the most common, mainly in healthy women; however, the microbiota composition can change rapidly, leading to infection or to a state in which potential pathogenic microorganisms co-exist with other commensals. In premenopausal women, urogenital infections, such as bacterial vaginosis and aerobic vaginitis, remain an important health problem. Treatment of these infections involves different kind of antibiotics; however, the recurrence rate remains high, and it must be also underlined that antibiotics are unable to spontaneously restore normal flora characterized by an abundant community of Lactobacilli. The main limitation is the inability to offer a long-term defensive barrier, thus facilitating relapses and recurrences. We report here the antimicrobial activities of two commercially existing Lactobacillus strains, Lactobacillus rhamnosus HN001 and Lactobacillus acidophilus GLA-14 strains and their combination (Respecta® probiotic blend) against four different pathogens responsible for both bacterial vaginosis ( Gardenerella vaginalis and Atopobium vaginae) and aerobic vaginitis ( Staphylococcus aureus and Escherichia coli) by co-culturing assay. The probiotic combination, even if resulting in a different microbicidal activity against the different strains tested, demonstrated the efficacy of combined Lactobacillus strain treatment.

Liposomal amphotericin B for the treatment of visceral leishmaniasis.

During the past decade, liposomal amphotericin B has been used with increasing frequency to treat visceral leishmaniasis (VL). The World Health Organization convened a workshop to review current knowledge and to develop guidelines for liposomal amphotericin B use for VL. In Europe, liposomal amphotericin B is widely used to treat VL. In Africa and Asia, the VL disease burden is high and drug access is poor; liposomal amphotericin B is available only through preferential pricing for nonprofit groups in East Africa. Clinical trials and experience demonstrate high efficacy and low toxicity for liposomal amphotericin B (total dose, 20 mg/kg) in immunocompetent patients with VL. Combination trials in areas with antileishmanial drug resistance, and treatment and secondary prophylaxis trials in VL-human immunodeficiency virus-coinfected patients, are important to safeguard the current armamentarium and to optimize regimens. The public health community should work to broaden access to preferential liposomal amphotericin B pricing by public sector VL treatment programs.

Increased CD154 expression in uninfected infants born to HIV-positive mothers exposed to antiretroviral prophylaxis.

Although prevention of mother-to-child HIV transmission by antiretroviral drugs has been shown to be effective, the short- and long-term effects of treatment are not well known. Several reports suggest that antiretroviral drugs act not only by inhibiting viral replication, but also by improving antiviral immunity. In particular, treatment with nucleoside analogs was found to increase CD40 ligand (CD40L; CD154) levels, an inducible molecule expressed on activated T lymphocytes. The present study investigated potential immunostimulatory effects of antiretroviral treatment (ART) in uninfected HIV-exposed infants, receiving either ante- or postnatal therapy to reduce the transmission rate. To this end, we analyzed CD40L expression in unstimulated lymphocytes from peripheral blood samples of uninfected infants vertically exposed to HIV and subjected to ART. The CD45 PanLeucogating strategy was applied in flow cytometry to analyze the lymphocytes of 41 cases and 64 age-matched infants, taken as control. We found increased CD154 expression on both CD4+ and CD8+ lymphocytes in ART-treated infants, compared with the controls. CD154 was apparently functional, because the expression of CD86 on monocytes was enhanced; moreover, inhibition of the CD40-CD40L interaction produced downmodulation of CD86. From these results, we conclude that CD4+ and CD8+ lymphocytes of HIV-exposed noninfected infants, who have been exposed to antiretroviral drugs in fetal and early life, display enhanced CD154 expression and costimulatory activity.

Impact of insulin resistance on cardiac and vascular function.

BACKGROUND: Insulin resistance (IR), constitutes an important cardiovascular risk factor and can cause ischemic heart disease. It can lead to left ventricular dysfunction with a mechanism independent of ischemic heart disease and it is closely associated with impaired vascular function. The aim of our study was to explore the impact of IR on cardiac and vascular function, in patients with cardiovascular risk factors but angiographically undamaged coronary arteries. METHODS: We studied 32 patients (62.06±11.19years) with cardiovascular risk factors. All patients underwent coronary angiography, echocardiography, Doppler ultrasound of carotid arteries and laboratory tests. Exclusion criteria were coronary artery disease detected by coronary angiography, diabetes mellitus, creatinine above 1.5mg/dl, atrial fibrillation or malignant arrhythmias, left-ventricular hypertrophy, valvular heart disease, ejection fraction below 50%. The presence of insulin resistance was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Each patient underwent a complete echocardiographic examination including Global Longitudinal Strain assessment and carotid artery ultrasound scan including measurement of arterial stiffness. RESULTS: The patients were divided into two groups based on the median value of HOMA-IR, the first group for values <4.14 and, the second, for values ≥4.14. Ejection fraction and diastolic function did not significantly differ between the two groups, whether in patients with higher levels of HOMA-IR (≥4.14) we observed a Global Longitudinal Strain (GLS) that was significantly reduced (-16.50±1.37% vs. -20.73±1.84%, p=0.0015) vascular stiffness, measured in the carotid arteries as pulse wave velocity (PWV) (9.70±1.75m/s vs. 7.40±1.89m/s, p=0.00148) that was increased. At multivariate analysis HOMA-IR was an independent predictor of myocardial dysfunction (GLS: coefficient 0.1156, p<0.0001). CONCLUSION: Insulin resistance is associated with subclinical myocardial and vascular alterations in patients without significant coronary artery disease, measured as a reduction of Global Longitudinal Strain, and increased arterial stiffness. Our results underscore the importance of studying the interaction between ventricular function and vessels, in the perspective of more effective preventive and therapeutic interventions.

Pharmacokinetic Profile of µSMIN Plus™, a new Micronized Diosmin Formulation, after Oral Administration in Rats.

Diosmin is a naturally occurring flavonoid present in citrus fruits and other plants belonging to the Rutaceae family. It is used for the treatment of chronic venous insufficiency (CVI) for its pheblotonic and vaso-active properties, safety and tolerability as well. The aim of the current in vivo study was to investigate the pharmacokinetic profile of a branded micronized diosmin (µSMIN Plus™) compared with plain micronized diosmin in male Sprague-Dawley rats. After oral administration by gastric gavage, blood samples were collected via jugular vein catheters at regular time intervals from baseline up to 24 hours. Plasma concentrations were assessed by LC/MS. For each animal, the following pharmacokinetic parameters were calculated using a non-compartmental analysis: maximum plasma drug concentration (Cmax), time to reach Cmax (Tmax), area under the plasma concentration-time curve (AUC0-last), elimination half-life (t½), and relative oral bioavailability (%F). The results of the current study clearly showed an improvement in the pharmacokinetic parameters in animals treated with µSMIN Plus™ compared with animals treated with micronized diosmin. In particular, µSMIN Plus™ showed a 4-fold increased bioavailability compared with micronized diosmin. In conclusion, the results from the current study provided a preliminary pharmacokinetic profile for µSMIN Plus™, which may represent a new tool for CVI management.