ECG monitoring of post-stroke occurring arrhythmias: an observational study using 7-day Holter ECG.

Post-stroke arrhythmias represent a risk factor for complications and worse prognosis after cerebrovascular events. The aims of the study were to detect the rate of atrial fibrillation (AF) and other cardiac arrhythmias after acute ischemic stroke, by using a 7-day Holter ECG which has proved to be superior to the standard 24-h recording, and to evaluate the possible association between brain lesions and arrhythmias. One hundred and twenty patients with cryptogenic ischemic stroke underwent clinical and neuroimaging assessment and were monitored with a 7-day Holter ECG. Analysis of the rhythm recorded over 7 days was compared to analysis limited at the first 24 h of monitoring. 7-day Holter ECG detected AF in 4% of patients, supraventricular extrasystole (SVEB) in 94%, ventricular extrasystole (VEB) in 88%, short supraventricular runs (SVRs) in 54%, supraventricular tachycardia in 20%, and bradycardia in 6%. Compared to the first 24 h of monitoring, 7-Holter ECG showed a significant higher detection for all arrhythmias (AF p = 0.02; bradycardia p = 0.03; tachycardia p = 0.0001; SVEB p = 0.0002; VEB p = 0.0001; SVRs p = 0.0001). Patients with SVRs and bradycardia were older (p = 0.0001; p = 0.035) and had higher CHA2DS2VASc scores (p = 0.004; p = 0.026) respectively, in the comparison with patients without these two arrhythmias. An association was found between SVEB and parietal (p = 0.013) and temporal (p = 0.013) lobe lesions, whereas VEB correlated with insular involvement (p = 0.002). 7-day Holter ECG monitoring proved to be superior as compared to 24-h recording for the detection of all arrhythmias, some of which (SVEB and VEB) were associated with specific brain areas involvement. Therefore, 7-day Holter ECG should be required as an effective first-line approach to improve both diagnosis and therapeutic management after stroke.

Germplasm evaluation to obtain inulin with high degree of polymerization in Mediterranean environment.

Long-chain length (DP) inulin-type fructans show pronounced beneficial effects to colon microbiota. In the past, cardoon roots for inulin production to fortify spaghetti gave very good results, but their harvest requires high costs. The aim of the work was to evaluate different types of inulin, extracted from cardoon roots and buds, topinambur tubers and chicory roots local populations in order to identify crops more suitable for high DP inulin production in Mediterranean environment. The inulin amount resulted in 115 (chicory), 390 (cardoon) and 550 g kg-1 of d.m. (topinambur). Both in cardoon roots and in topinambur tubers the DP was very high. With the aim to produce a functional food, substituting inulin in staple food tubers of topinambur could be a good alternative to cardoon roots, due to the biological cycle of the plant (annual vs poliennal), the lowest costs of harvest and the good amounts of high DP inulin.

Alemtuzumab treatment of multiple sclerosis in real-world clinical practice: A report from a single Italian center.

BACKGROUND: Alemtuzumab, is a compound approved for highly active MS, and, in Europe, employed after the use of other disease-modifying treatments (DMTs) with an escalation approach or used as a first therapeutic option. The occurrence of secondary autoimmune adverse events and or infections can differ depending on the employed approach. OBJECTIVE: To evaluate the efficacy and safety of alemtuzumab in real-world MS population that encompassed patients previously treated with other DMTs. METHODS: 35 patients, treated with alemtuzumab in a single MS Center, were followed for at least 36 months. The study investigated the prevalence of patients reaching the phase of the non-active disease (NEDA-3). All the adverse events were also reported, and correlations assessed. RESULTS: At the 36-month follow-up, 66,7% of patients achieved the NEDA-3 status, 90,5% of the patients were relapse-free, 85,7% showed no signs of disability progression, nor signs of MRI activity. Adverse events were observed in 45,7% of the patients and ranked as severe in 23% of them. Cases of autoimmune hemolytic anemia (AIHA), pancytopenia, viral hepatitis E, and noninfectious meningo-encephalomyelitis were found and reported. For these complications, the post hoc analysis showed possible interactive factors and causality related to previous DMT treatments. CONCLUSIONS: In a real-world MS population like the one investigated in our study, alemtuzumab was found to be an effective treatment when employed as an escalation or rescue therapy. The compound exhibits a variable safety profile and frequent adverse events that are likely depending on previous treatments and their impact on the immune system.

Cloves syndrome: a case report and perinatal diagnostic findings.

We report a neonate with prenatal ultrasound imaging features suggestive of CLOVES syndrome, confirmed postnatally by clinical and imaging findings of the constellation of truncal overgrowth, cutaneous capillary malformations, lymphatic and musculoskeletal anomalies. The clinical, radiological and histopathological findings noted in our patient help differentiate from other overgrowth syndromes such as Proteus syndrome. We report perinatal findings and add new clinical findings of this rare syndrome.

Cesarean delivery rates in Down syndrome pregnancies.

OBJECTIVES: Data on rates of cesarean delivery among pregnancies diagnosed with genetic syndromes remains limited. We examined the cesarean delivery rates for Down syndrome pregnancies over a 10-year period in the US. METHODS: We used data from the 1995-2004 US delivery data files to examine cesarean delivery rates in singleton pregnancies (at ≥20 weeks' gestation) with and without Down syndrome. We further examined if the rates of cesarean deliveries in primary and repeat cesarean deliveries among Down syndrome pregnancies differed based on the presence or absence of major structural abnormalities or stillbirth or gestational age at delivery. RESULTS: There were 35 million singleton deliveries of which 19186 were diagnosed at birth with Down syndrome (1 in 2000 births after 20 weeks gestation). The primary cesarean delivery rates were higher among Down syndrome pregnancies (17.5% in 1995 and 21.5% in 2004) compared to non-Down syndrome pregnancies (12.3% in 1995 and 16.6% in 2004). Temporal trends for cesarean deliveries were steeper among Down syndrome pregnancies with gastrointestinal and heart abnormalities than in Down syndrome cases without abnormalities. Higher cesarean delivery rates were also noted among Down syndrome pregnancies ending in third trimester live born than in control. CONCLUSION: In the US, cesarean deliveries in Down syndrome pregnancies increases over time and is greater when Down syndrome is associated with structural abnormalities and delivered during the third trimester of pregnancy.

Ectopia cordis.

We report on a preterm male newborn with complete ectopia cordis associated with Cantrell's syndrome. The neonate had an ectopia cordis involving defects of the lower sternum, supraumbilical abdominal wall, anterior portion of the diaphragm, and diaphragmatic portion of the pericardium associated with complex congenital heart defects. The infant died shortly after birth. We discuss this case and review the literature.

The sea-air exchange of mercury (Hg) in the marine boundary layer of the Augusta basin (southern Italy): concentrations and evasion flux.

The first attempt to systematically investigate the atmospheric mercury (Hg) in the MBL of the Augusta basin (SE Sicily, Italy) has been undertaken. In the past the basin was the receptor for Hg from an intense industrial activity which contaminated the bottom sediments of the Bay, making this area a potential source of pollution for the surrounding Mediterranean. Three oceanographic cruises have been thus performed in the basin during the winter and summer 2011/2012, where we estimated averaged Hgatm concentrations of about 1.5±0.4 (range 0.9-3.1) and 2.1±0.98 (range 1.1-3.1) ng m(-3) for the two seasons, respectively. These data are somewhat higher than the background Hg atm value measured over the land (range 1.1±0.3 ng m(-3)) at downtown Augusta, while are similar to those detected in other polluted regions elsewhere. Hg evasion fluxes estimated at the sea/air interface over the Bay range from 3.6±0.3 (unpolluted site) to 72±0.1 (polluted site of the basin) ng m(-2) h(-1). By extending these measurements to the entire area of the Augusta basin (~23.5 km(2)), we calculated a total sea-air Hg evasion flux of about 9.7±0.1 g d(-1) (~0.004 tyr(-1)), accounting for ~0.0002% of the global Hg oceanic evasion (2000 tyr(-1)). The new proposed data set offers a unique and original study on the potential outflow of Hg from the sea-air interface at the basin, and it represents an important step for a better comprehension of the processes occurring in the marine biogeochemical cycle of this element.

Chemical stability of tramadol hydrochloride injection admixed with selected pain drugs.

BACKGROUND: Tramadol hydrochloride (HCl) and ketorolac tromethamine are analgesic drugs, which are commonly used in combination in postoperative pain management. According to some studies, metoclopramide and magnesium sulfate (MgSO(4)) as adjuvant agents can improve analgesia and decrease the need for other pain drugs. MATERIALS AND METHODS: The chemical stability of tramadol HCl combined with ketorolac tromethamine and metoclopramide HCl has been studied using a stability-indicating high-performance liquid chromatographic assay method. Calibration curves were produced using linear regression of the peak area against concentration of each drug, with an r(2) value ≥ 0.96. Our aim was to investigate the stability of admixture solution of tramadol HCl combined with ketorolac tromethamine and metoclopramide HCl for 48 h (25°C) and 5 days (5°C), with MgSO(4), which has never been assessed. RESULTS: Data obtained for admixtures prepared and stored at temperatures of 25°C and 5°C, show that all drugs have reached at least 98% of the initial concentration. CONCLUSIONS: For the purpose of pre-preparing drug admixtures to use with confidence, tramadol HCl infusions may be prepared in advance and then thawed before use in clinical units. On the basis of our results, the intravenous mixture of tramadol (7.69 mg/mL), metoclopramide (0.19 mg/mL), ketorolac (1.15 mg/mL), and magnesium sulfate (77 mg/mL) may be considered for a possible commercial formulation.

A practical and transferable methodology for dose estimation in irradiated spices, based on thermoluminescence dosimetry.

The thermoluminescence technique is recommended by the European Committee for Standardization for the detection of irradiated food containing silicates as contaminants. In this work, the applicability of the thermoluminescence technique as a quantitative method to assess the original dose in irradiated oregano was studied; the additive-dose method was used, with reirradiation doses up to 600 Gy. The proposed new procedure allows to clearly discriminate irradiated from unirradiated samples, even after one year storage, and it gives an acceptable estimation of the original dose; the overall modified procedure requires only one day to be completed.

Antimicrobial and antistaphylococcal biofilm activity from the sea urchin Paracentrotus lividus.

AIMS: Staphylococcal biofilm-associated infections are resistant to conventional antibiotics. Consequently, new agents are needed to treat them. With this aim, we focused on the effector cells (coelomocytes) of the sea urchin Paracentrotus lividus immune system. METHODS AND RESULTS: We tested the activity of the 5-kDa peptide fraction of the cytosol from coelomocytes (5-CC) against a group of Gram-positive, Gram-negative bacteria and fungi. We determined minimal inhibitory concentrations (MICs) ranging from 253.7 to 15.8 mg ml(-1). We observed an inhibitory activity and antibiofilm properties of 5-CC against staphylococcal biofilms of reference strains Staphylococcus epidermidis DSM 3269 and Staphylococcus aureus ATCC 29213. The antimicrobial efficacy of 5-CC against the biofilms of clinical strain Staph. epidermidis 1457 was also tested using live/dead staining in combination with confocal laser scanning microscopy. At a sub-MIC concentration (31 x 7 mg ml(-1)) of 5-CC the formation of young (6-h old) and mature (24-h old) staphylococcal biofilms was inhibited. CONCLUSIONS: The biological activity of 5-CC could be attributed to three peptides belonging to the sequence segment 9-41 of a beta-thymosin of P. lividus. SIGNIFICANCE AND IMPACT OF THE STUDY: The effector cells of P. lividus represent an interesting source of marine invertebrates-derived antimicrobial agents in the development of new strategies to treat staphylococcal biofilms.

Efficacy of genistein aglycone on some cardiovascular risk factors and homocysteine levels: A follow-up study.

BACKGROUND AND AIM: Recent evidence suggests that genistein aglycone may act beneficially on surrogate cardiovascular risk markers in postmenopausal women. We assessed the effects of genistein aglycone on some cardiovascular risk factors and homocysteine levels after 3-years of continued therapy in a cohort of osteopenic, postmenopausal women. METHODS AND RESULTS: The parent study was a randomized, double-blind, placebo-controlled trial involving 389 postmenopausal women with low bone mass for 24 months. Subsequently, a subcohort (138 patients) continued therapy for an additional year. Participants received 54mg of genistein aglycone (n=71) or placebo (n=67), daily. Both arms received calcium and vitamin D(3) in therapeutic doses. Moreover, 4 weeks before randomization procedures and during our follow-up study, all patients received dietary instructions in an isocaloric fat-restricted diet. Blood lipid profiles, fasting glucose and insulin, insulin resistance (HOMA-IR), fibrinogen, osteoprotegerin (OPG) and homocysteine at baseline and after 24 and 36 months of treatment were measured. Compared to placebo, genistein significantly decreased fasting glucose and insulin, HOMA-IR, fibrinogen and homocysteine after 24 and 36 months of treatment. By contrast, isoflavone administration did not affect high-density lipoprotein cholesterol and triglycerides though serum OPG was higher in the genistein recipients. There were no differences in adverse events or discomfort between groups. Results on routine biochemical, liver function, and hematologic testing did not change over time in placebo or genistein group. CONCLUSIONS: After 3-years of treatment, genistein aglycone plus calcium, vitamin D(3) and a healthy diet showed positive effects on some cardiovascular risk factors and homocysteine levels in a cohort of postmenopausal women with low bone mass.

Recurrent peptic ulcer disease in a pediatric patient with type 1 neurofibromatosis and primary ciliary dyskinesia.

Neurofibromatosis type 1 is an autosomal dominant neurocutaneous disorder with characteristic features of skin and central nervous system involvement. Gastrointestinal complications are rare, especially during childhood. In adults, only two cases of peptic ulcer have been reported in neurofibromatosis, both due to Zollinger-Ellison syndrome. Peptic ulcer disease (PUD) may be primary or secondary in nature and it may be life threatening in the acute phase due to the risk of perforation. A case of recurrent gastrointestinal hemorrhage in a child with systemic neurofibromatosis and primary ciliary dyskinesia (PCD) is presented. The upper gastrointestinal endoscopy revealed the presence of multiple gastric ulcers. The ulcers scarred after the long-term administration of a proton pump inhibitor (PPI), but recurred after the suspension. Laboratory and imaging studies excluded Zollinger-Ellison syndrome and other known causes of PUD, suggesting a potential role of neurofibromatosis itself and primary ciliary dyskinesia in developing of recurrent PUD. As early diagnosis of PUD is vital for patient survival, this case report highlights the possible association of neurofibromatosis and PCD with this condition, responsive to PPI therapy and the potential need of gastric protection before complications arise.

Flavocoxid, a dual inhibitor of cyclooxygenase and 5-lipoxygenase, blunts pro-inflammatory phenotype activation in endotoxin-stimulated macrophages.

BACKGROUND AND PURPOSE: The flavonoids, baicalin and catechin, from Scutellaria baicalensis and Acacia catechu, respectively, have been used for various clinical applications. Flavocoxid is a mixed extract containing baicalin and catechin, and acts as a dual inhibitor of cyclooxygenase (COX) and 5-lipoxygenase (LOX) enzymes. The anti-inflammatory activity, measured by protein and gene expression of inflammatory markers, of flavocoxid in rat peritoneal macrophages stimulated with Salmonella enteritidis lipopolysaccharide (LPS) was investigated. EXPERIMENTAL APPROACH: LPS-stimulated (1 microg.mL(-1)) peritoneal rat macrophages were co-incubated with different concentrations of flavocoxid (32-128 microg.mL(-1)) or RPMI medium for different incubation times. Inducible COX-2, 5-LOX, inducible nitric oxide synthase (iNOS) and inhibitory protein kappaB-alpha (IkappaB-alpha) levels were evaluated by Western blot analysis. Nuclear factor kappaB (NF-kappaB) binding activity was investigated by electrophoretic mobility shift assay. Tumour necrosis factor-alpha (TNF-alpha) gene and protein expression were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay respectively. Finally, malondialdehyde (MDA) and nitrite levels in macrophage supernatants were evaluated. KEY RESULTS: LPS stimulation induced a pro-inflammatory phenotype in rat peritoneal macrophages. Flavocoxid (128 microg.mL(-1)) significantly inhibited COX-2 (LPS = 18 +/- 2.1; flavocoxid = 3.8 +/- 0.9 integrated intensity), 5-LOX (LPS = 20 +/- 3.8; flavocoxid = 3.1 +/- 0.8 integrated intensity) and iNOS expression (LPS = 15 +/- 1.1; flavocoxid = 4.1 +/- 0.4 integrated intensity), but did not modify COX-1 expression. PGE(2) and LTB(4) levels in culture supernatants were consequently decreased. Flavocoxid also prevented the loss of IkappaB-alpha protein (LPS = 1.9 +/- 0.2; flavocoxid = 7.2 +/- 1.6 integrated intensity), blunted increased NF-kappaB binding activity (LPS = 9.2 +/- 2; flavocoxid = 2.4 +/- 0.7 integrated intensity) and the enhanced TNF-alpha mRNA levels (LPS = 8 +/- 0.9; flavocoxid = 1.9 +/- 0.8 n-fold/beta-actin) induced by LPS. Finally, flavocoxid decreased MDA, TNF and nitrite levels from LPS-stimulated macrophages. CONCLUSION AND IMPLICATIONS: Flavocoxid might be useful as a potential anti-inflammatory agent, acting at the level of gene and protein expression.

Genistein aglycone reverses glucocorticoid-induced osteoporosis and increases bone breaking strength in rats: a comparative study with alendronate.

BACKGROUND AND PURPOSE: Glucocorticoid-induced osteoporosis (GIO) is the leading cause of secondary osteoporosis. Clinical evidence suggests a role for genistein aglycone in the treatment of post-menopausal osteopenia although proof of efficacy in comparison with currently available treatments is still lacking. To clarify this issue, we investigated the effects of genistein on bone compared with alendronate in experimental GIO. EXPERIMENTAL APPROACH: A total of 28 female Sprague-Dawley rats were used. GIO was induced by daily injections of methylprednisolone (MP; 30 mg x kg(-1) s.c.) for 60 days. Sham GIO animals (Sham-MP) were injected daily with the MP vehicle. At the end of the osteoporosis development period, MP rats were randomized to receive: vehicle (n= 7), genistein aglycone (5 mg x kg(-1) s.c.; n= 7) or alendronate (0.03 mg x kg(-1) s.c.; n= 7). Treatment lasted 60 days. Sham-MP animals were treated with vehicle for an additional 60 days. At the beginning and at the end of treatments, animals were examined for bone mineral density and bone mineral content. Bone-alkaline phosphatase and carboxy-terminal collagen cross links were determined; femurs were removed and tested for breaking strength and histology. KEY RESULTS: Genistein aglycone showed a greater increase in bone mineral density, bone mineral content and in breaking strength than alendronate and significantly increased bone-alkaline phosphatase (bone formation marker), reduced carboxy-terminal collagen cross links (bone resorption marker), compared with alendronate. Both treatments improved bone histology and the histological score. CONCLUSION AND IMPLICATIONS: The results strongly suggest that the genistein aglycone might be an alternative therapy for the management of secondary osteoporosis.

Effects of genistein aglycone in osteoporotic, ovariectomized rats: a comparison with alendronate, raloxifene and oestradiol.

BACKGROUND AND PURPOSE: Genistein aglycone positively affects bone loss in postmenopausal women, but bone quality data are still lacking. To clarify this, we investigated the effects of genistein compared with alendronate, raloxifene and oestradiol in an animal model of established osteoporosis. EXPERIMENTAL APPROACH: Six months after ovariectomy, 96 ovariectomized (OVX) rats were divided into 8 equal groups, randomized to treatments (genistein aglycone (1 and 10 mg kg(-1) s.c.); alendronate (0.003 and 0.03 mg kg(-1) s.c.); raloxifene hydrochloride (0.05 and 0.5 mg kg(-1) s.c.); 17-alpha-ethinyl oestradiol (0.003 and 0.03 mg kg(-1) s.c.)) for 12 weeks. Untreated OVX (n=12) and sham OVX (n=12) were used as controls. At the beginning and end of treatment, bone mineral density (BMD) and bone mineral content (BMC) were assessed. At the end of the experiment, calcium, phosphorus, bone-alkaline phosphatase (b-ALP), collagen C-telopeptide (CTX), osteoprotegerin (OPG) and soluble receptor activator of nuclear factor-kappaB ligand (sRANKL) were assayed. Femurs were removed and tested for breaking strength and histology. KEY RESULTS: Genistein (10 mg kg(-1)) showed a greater increase in both BMD (P<0.0001 vs OVX) and BMC than all the other treatments. Moreover, genistein significantly increased breaking strength, bone quality, b-ALP (P<0.0001 vs OVX) and OPG, and reduced CTX and sRANKL compared with the other treatments at all dose levels. CONCLUSIONS AND IMPLICATIONS: The results strongly suggest that the genistein aglycone might be a new therapy for the management of postmenopausal osteoporosis in humans.

In vitro anti-biofilm activity of Boswellia spp. oleogum resin essential oils.

AIMS: To evaluate the anti-biofilm activity of the commercially available essential oils from two Boswellia species. METHODS AND RESULTS: The susceptibility of staphylococcal and Candida albicans biofilms was determined by methyltiazotetrazolium (MTT) staining. At concentrations ranging from 217.3 microg ml(-1) (25% v/v) to 6.8 microg ml(-1) (0.75% v/v), the essential oil of Boswellia papyrifera showed considerable activity against both Staphylococcus epidermidis DSM 3269 and Staphylococcus aureus ATCC 29213 biofilms. The anti-microbial efficacy of this oil against S. epidermidis RP62A biofilms was also tested using live/dead staining in combination with fluorescence microscopy, and we observed that the essential oil of B. papyrifera showed an evident anti-biofilm effect and a prevention of adhesion at sub-MIC concentrations. Boswellia rivae essential oil was very active against preformed C. albicans ATCC 10231 biofilms and inhibited the formation of C. albicans biofilms at a sub-MIC concentration. CONCLUSIONS: Essential oils of Boswellia spp. could effectively inhibit the growth of biofilms of medical relevance. SIGNIFICANCE AND IMPACT OF THE STUDY: Boswellia spp. essential oils represent an interesting source of anti-microbial agents in the development of new strategies to prevent and treat biofilms.

Atractyligenine chemistry, Part VI: Synthesis and biological activities of atractyligenine derivatives.

Derivatives of atractyligenine, the aglycone of atractyloside, were tested in vitro for their antimicrobial and antiproliferative activity against K-562 (human chronic myelogeneous leukemia), HL-60 (human leukemia) and MCF-7 (human breast adenocarcinoma) cell lines. The most active compound showed IC50 values in the range 0.8-6.9 microM.

Detection and localisation of disulphide bonds in a synthetic peptide reproducing the sequence 1-30 of Par j 1.0101 by electrospray ionisation mass spectrometry.

The structural characterisation of a synthetic peptide reproducing the sequence 1-30 of Par j 1.0101, a major allergenic protein present in the pollen of Parietaria judaica, by combined use of chemical and enzymatic cleavage, reversed-phase high-performance liquid chromatography and electrospray ionisation mass spectrometry (ESI-MS), is described. Direct ESI-MS of the synthetic peptide after reaction with methyl iodide showed that the product is a mixture of two peptides: one form in which two out of the four cysteine residues present in the sequence are oxidised and a minor amount of another form in which all the cysteines are fully reduced. It was ascertained, using the combined procedure indicated above and without prior separation of the two species, that the disulphide bond in the partially oxidised form is located between cysteines 29 and 30. These results show the usefulness of this approach for characterising synthetic peptides containing multiple cysteine residues in the sequence.

Traditional medicine as a source of new therapeutic agents against psoriasis.

In the frame of traditional medicine, the use in the treatment of psoriasis of some plants typical of the flora of Sicily is reported. A preliminary search on some plants used for the treatment of psoriasis in Asia, South America and Africa is also reported.