A pilot study on secondary anemia in "frailty" patients treated with Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine: safety of treatment explored by HRV non-linear analysis as predictive factor of cardiovascular tolerability.

OBJECTIVE: Iron deficiency anemia (IDA) in patients with heart disease is correlated with decreased exercise capacity and poor health-related quality of life, and predicts worse cardiovascular outcomes, especially for elderly patients. IDA can worsen cardiac function that can be monitored with Heart Rate Variability (HRV) analysis, providing important information about cardiac health. In a recent study we explored the effect and the tolerability of the administration of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel Forte®) in "frailty" patients with secondary anemia and low kidney failure, by analysing the HRV frequency domain. The aim of the present study is the further confirmation of the safety of the already evaluated intervention, by analysing non-linear domain of HRV. PATIENTS AND METHODS: In this pilot study we enrolled 52 "frailty" elderly patients, with a recent diagnosis of secondary anemia due to iron deficiency, with Class II New York Heart Association (NYHA) hypertensive heart disease, low kidney failure, and atherosclerosis. The patients were divided in 2 groups: Group A (N=23 patients) received oral administration of Ferric Sodium EDTA in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel Forte®) 2 tabs/day, containing 60 mg of Fe3+, for 24 days; Group B (N=29 patients) received intravenous administration of ferrous gluconate 63 mg/day added to saline solution, while they were hospitalized (15±5 days). We evaluated laboratory values of hemoglobin (Hb) and sideremia levels. Furthermore, we measured ECG signals before and after treatment, using non-linear analysis techniques. RESULTS: Both intravenous and oral treatments evaluated in this study, were effective and safe about the cardiovascular risk in "frailty" elderly patients, as resulted from non-linear HRV analysis. Efficacy results showed that hemoglobin and sideremia levels after treatments are significantly increased. The HRV non-linear analysis showed that all parameters evaluated, except for the SD1 values in the Group A, were not affected by treatments, confirming the absence of cardiovascular risk of the therapy. CONCLUSIONS: Non-linear HRV evaluation confirmed that oral administration of Ferric Sodium EDTA, in combination with vitamin C, folic acid, copper gluconate, zinc gluconate and selenomethionine (Ferachel forte®) did not impact the cardiovascular risk, without causing adverse events typically reported with other iron supplementation therapies, both oral and intravenous.

New high intensity fibreoptic phototherapy devices in healthy newborns: a single pad wrapped around the neonate body in comparison with a double pad device.

BACKGROUND: Fibreoptic Phototherapy (FPT) allows to lower total serum bilirubin (TSB) levels in healthy neonates maintained in rooming-in with their mothers. The 2004 Cochrane review showed that, differently from preterm neonates, FPT was not as effective as traditional phototherapy in term neonates (TN), unless the simultaneous utilization of two FPT devices. Aim of this study was to compare the efficacy of two FPT devices, both equipped with a single light-emitting diode (LED): the first one has a single large pad wrapped around the infant body (Bilisoft, GE Health Care) (device A), the second one is a double-pad phototherapy device (BiliCocoon, CremascolieIris) (device B). METHODS: We studied 172 healthy neonates with non-hemolytic hyperbilirubinaemia: 57 TN and 57 late preterm neonates (LPN) treated with device A (Group 1); 47 TN and 11 LPN treated with device B (Group 2). We evaluated the differences between groups by the Student's t-test for continuous variables and by chi square test for categorical data. A two tailed p < 0.05 was considered significant. RESULTS: There were no differences in term of duration of FPT, TSB hourly reduction, percentage of TSB reduction after FPT, TSB maximum rebound, percentage of TSB increase after FPT discontinuation and number of after-discharge checks. Two neonates treated with device B showed no decrease in TSB values during FPT. Seven infants treated with device B experienced hyperpyrexia. CONCLUSIONS: The two LED FPT devices were both effective in lowering TSB either in TN or LPN. Device A was effective in all treated neonates without negative side effects during treatment; device B was effective in all but 2 infants and 12% of the neonates in the same group experienced hyperpyrexia. According to our results, the single big pad wrapped around the infant body has the same efficacy as a double FPT device in TN and LPN.

The unpredictability of seasonal variations in serum vitamin D levels in children with asthma and/or rhinitis.

BACKGROUND: Some studies have showed that seasonality is an important determinant of vitamin D (vitD) status. OBJECTIVE: We evaluated whether there are differences in individual trends of serum vitD level over one year in asthmatic and rhinitic children. MATERIALS AND METHODS: Ninety-two asthmatic and rhinitic paediatric patients were followed up for one year and their serum vitD level was detected at three-month intervals, once in each season. RESULTS: We observed higher vitD levels at the end of summer and lower at the end of winter. However, the individual seasonal trend was very variable and unpredictable. If it is true that in a given season the majority of patients followed one direction (increase or decrease of serum vitD levels), nevertheless a substantial percentage behaved differently and unpredictably. For example, at the end of spring, 70% of patients showed an increase in serum vitD levels, but 30% showed a decrease. In addition, five individuals had a value ≥50ng/ml in September and showed serum vitD levels ≥30ng/ml throughout the year; 16 patients presented vitD value ≥40ng/ml in September and always had ≥20ng/ml in the other months. CONCLUSIONS: The wide and unpredictable variability of the individual trend of serum vitD levels should be taken into account before deciding whether or not a drug supplementation is appropriate.

How social media meet patients’ questions: YouTube™ review for mouth sores in children.

Recurrent aphthous stomatitis (RAS) is one of the most common causes of mouth sores in children so the management of this condition is a matter of great importance. YouTube™ is increasingly being used by patients to obtain health-related information. The aim of this work is to examine the quality of information offered by YouTube™ about mouth sores in children (MSC). Searching the term ‘mouth sores in children’, (MSC) displayed 12.300 results. Of the top 60 videos analyzed, 31 were excluded following exclusion criteria. The major source of upload was from healthcare information channels (HC-41,38%), followed by individual users (HP-25.59%), healthcare professionals (IU-17.24%) and generalist information channels (HC-13.78%); 20.69% of them deal with predisposing factors, and related pathologies, the majority of these propose home remedies (60.72%) rather than topical analgesic drugs (21.43%), antimicrobials (7.14%) and topical steroids (3.57). Most of the videos analyzed were slightly useful (68.97%). Information about mouth sores in children on YouTube™ was poor regardless of the upload source. Analyzing health content on social platforms is a starting point for providing greater quality of health-related information.

Safety of an accelerated build-up phase with pollen allergoids: a retrospective study

No disponible

Childhood neurofibromatosis type 2 (NF2) and related disorders: from bench to bedside and biologically targeted therapies.

Neurofibromatosis type 2 [NF2; MIM # 101000] is an autosomal dominant disorder characterised by the occurrence of vestibular schwannomas (VSs), schwannomas of other cranial, spinal and cutaneous nerves, cranial and spinal meningiomas and/or other central nervous system (CNS) tumours (e.g., ependymomas, astrocytomas). Additional features include early onset cataracts, optic nerve sheath meningiomas, retinal hamartomas, dermal schwannomas (i.e., NF2-plaques), and (few) café-au-lait spots. Clinically, NF2 children fall into two main groups: (1) congenital NF2 - with bilateral VSs detected as early as the first days to months of life, which can be stable/asymptomatic for one-two decades and suddenly progress; and (2) severe pre-pubertal (Wishart type) NF2- with multiple (and rapidly progressive) CNS tumours other-than-VS, which usually present first, years before VSs [vs. the classical adult (Gardner type) NF2, with bilateral VSs presenting in young adulthood, sometimes as the only disease feature]. Some individuals can develop unilateral VS associated with ipsilateral meningiomas or multiple schwannomas localised to one part of the peripheral nervous system [i.e., mosaic NF2] or multiple non-VS, non-intradermal cranial, spinal and peripheral schwannomas (histologically proven) [schwannomatosis]. NF2 is caused by mutations in the NF2 gene at chromosome 22q12.1, which encodes for a protein called merlin or schwannomin, most similar to the exrin-readixin-moesin (ERM) proteins; mosaicNF2 is due to mosaic phenomena for the NF2 gene, whilst schwannomatosis is caused by coupled germ-line and mosaic mutations either in the SMARCB1 gene [SWNTS1; MIM # 162091] or the LZTR1 gene [SWNTS2; MIM # 615670] both falling within the 22q region and the NF2 gene. Data driven from in vitro and animal studies on the merlin pathway [e.g., post-translational and upstream/downstream regulation] allowed biologically targeted treatment strategies [e.g., Lapatinib, Erlotinib, Bevacizumab] aimed to multiple tumour shrinkage and/or regression and tumour arrest of progression with functional improvement.

Microcosm biofilms originating from children with different caries experience have similar cariogenicity under successive sucrose challenges.

OBJECTIVES: The source of saliva inocula and the individual characteristics of saliva donors could affect the cariogenic activity of in vitro biofilms, but this could also be modulated by environmental determinants, such as the frequency of sugar consumption. Therefore, the aim of this study was to compare the cariogenicity of microcosm biofilm growths from the saliva of caries-free (CF) children, children with early childhood caries (ECC) and with severe ECC (S-ECC), under regular sucrose exposure. METHODS: Microcosm plaque biofilms were initiated from the saliva of CF, ECC and S-ECC children. Biofilms were grown in 24-well microplates on bovine enamel discs for up to 10 days in artificial saliva, which was replaced daily. Growth conditions comprised cariogenic challenge (artificial saliva supplemented with 1% sucrose 6 h/day) or no cariogenic challenge. Daily pH was obtained from the artificial saliva, and after the experimental period, the biofilm formed on the enamel discs was collected for microbiological analyses. Mineral loss in enamel discs was estimated by percentage of surface hardness change. RESULTS: Overall, no statistically significant differences were found among saliva sources (p > 0.05). Streptococcus mutans and lactobacilli counts increased in the biofilms grown under cariogenic challenge (p < 0.05), while a substantial decrease in the artificial saliva pH was detected under the same condition (p < 0.001). Higher demineralization (p < 0.001) was observed under sucrose exposure regardless of caries experience of children. CONCLUSIONS: While the sucrose exposure determined the cariogenicity of the biofilms, the caries experience of children who provided the inocula did not affect mineral loss associated with these biofilms.

Expression of Lactobacillus brevis IOEB 9809 tyrosine decarboxylase and agmatine deiminase genes in wine correlates with substrate availability.

AIMS: Lactobacillus brevis IOEB 9809 is able to produce both tyramine and putrescine via tyrosine decarboxylase and agmatine deiminase enzymes, respectively, when cultured on synthetic media. The aims of this study were to assess the expression of L. brevis IOEB 9809 tdc and aguA1 genes, during wine fermentation and to evaluate the effect of substrate availability and pH on tdc and aguA1 expression, as well as on biogenic amine production and L. brevis viability. METHODS AND RESULTS: The relative expression of L. brevis IOEB 9809 tdc and aguA1 genes was analysed in wine by quantitative real-time RT-PCR (qRT-PCR) during a period of incubation of 30 days. Cell viability, pH values, putrescine and tyramine concentration were monitored throughout the experiments. CONCLUSIONS: The wine trials indicated that L. brevis IOEB 9809 is able to produce both tyramine and putrescine during wine fermentation. Increased cell viability was also observed in wine supplemented with tyrosine or agmatine. qRT-PCR analysis suggests a strong influence of substrate availability on the expression of genes coding for tyrosine decarboxylase and agmatine deiminase in L. brevis IOEB 9809. Less evident is the relationship between putrescine and tyramine production and tolerance to wine pH. SIGNIFICANCE AND IMPACT OF STUDY: To our knowledge, this study represents the first assessment of relative expression of L. brevis IOEB 9809 genes involved in biogenic amine production in wine. Furthermore, an effect of biogenic amine production on viability of L. brevis during wine fermentation was established.

Antioxidant and cytotoxic activities of carob tree fruit pulps are strongly influenced by gender and cultivar.

Extracts from fruit pulps of six female cultivars and two hermaphrodite Portuguese carob trees [(Ceratonia siliqua L., Fabaceae)] exhibited strong antioxidant activity and were rich in phenolic compounds. The extracts decreased the viability of different human cancer cell lines on a dose- and time-dependent manner. Gender and cultivar significantly influenced the chemical content and the biological activities of the extracts. Extracts from hermaphrodite trees had a higher content of phenolic compounds, and exhibited higher antioxidant and cytotoxic activities. Among females, cv. Aida had the highest radical scavenging activity and total content of phenolics, Mulata the highest capacity to inhibit lipid oxidation and Gasparinha the strongest cytotoxic activity on HeLa cells. The decrease in cell viability was associated with apoptosis on HeLa and MDA-MB-231 lines. (+)-Catechin and gallic acid (GA) were the main compounds identified in the extracts, and GA contributed to the antioxidant activity. Our results show that the antioxidant and cytotoxic activities of carob tree fruit pulps are strongly influenced by gender and cultivar, and provide new knowledge about the advantages of hermaphrodite trees over female cultivars, namely, as a source of compounds with biological interest, which may represent an increase of their agronomic interest.

Effect of acute load of grapefruit juice on urinary excretion of citrate and urinary risk factors for renal stone formation.

The effect of citrus fruit juice ingestion on the risk of calcium oxalate stone formation is still debated. The present study was undertaken to investigate changes in urinary stone risk factors after administration of a soft drink containing grapefruit juice. Seven healthy subjects, with no history of kidney stones, were submitted to an acute oral load (20 ml/kg body weight over 60 min) of a soft drink containing grapefruit juice diluted (10%) in mineral water. After a 7-day wash-out period, each subject underwent an oral load with mineral water alone under the same conditions. Urine specimens were collected before (for 120 min) and after each oral fluid load (for 180 min). Urinary flow was significantly increased after both grapefruit juice (46+/-26 vs 186+/-109 ml/h, p = 0.01) and mineral water (42+/-16 vs 230+/-72 ml/h, p=0.001) compared to baseline. Compared to mineral water, grapefruit juice significantly (p=0.021) increased urinary excretion of citrate (25.8+/-9.3 vs 18.7+/-6.2 mg/h), calcium (6.7+/-4.3 vs 3.3+/-2.3 mg/h, p=0.015) and magnesium (2.9+/-1.5 vs 1.0+/-0.7 mg/h, p=0.003). Citrus fruit juices could represent a natural alternative to potassium citrate in the management of nephrolithiasis, because they could be better tolerated and cost-effective than pharmacological calcium treatment. However, in order to obtain a beneficial effect in the prevention of calcium renal stones a reduced sugar content is desirable to avoid the increase of urinary calcium due to the effect of sugar supplementation.

Essential oils from micropropagated plants of Lavandula viridis.

The essential oils of Lavandula viridis were analysed by GC and GC-MS. Comparisons were made between three types of plant material from the same clone: field-grown plant, in vitro shoot cultures and micropropagated plants of the same clone. The most common components usually found in lavender oils were present in the oil samples analysed and more than 45 constituents were identified, representing more than 80% of the essential oil. The essential oils analysed consisted mainly of monoterpenes (75.4-76.3%), where oxygenated and hydrocarbons identified ranged from 41.8 to 57.3% and 18.1 to 34.2%, respectively. The major components found were 1.8-cineole (18.2-25.1%), camphor (9.1-15.7%), alpha-pinene (8.8-14.1%), borneol (4.1-4.8%), beta-pinene (1.2-5.6%), delta 3-carene (1.0-6.5%) and alpha-terpineol (0.8-4.2%). The monoterpene fraction of the in vitro shoot cultures showed different relative amounts of hydrocarbons and oxygenated components in relation to the parent plant and to micropropagated plants. In the sesquiterpene hydrocarbon fraction of the oil samples analysed (6.1-8.2%), 7-epi-alpha-selinene (1.6-4.8%) was the most important component and the oxygenated sesquiterpenes were found in small amounts (1.1-1.7%). The essential oils from field-grown plants of L. viridis, when compared with those obtained from in vitro shoot cultures or micropropagated plants of the same clone, demonstrated that the same major components were found without significant compositional variations.

Prolonged molecular remission in advanced acute promyelocytic leukaemia after treatment with gemtuzumab ozogamicin (Mylotarg CMA-676).

We report a patient with acute promyelocytic leukaemia (APL) who received two doses of gemtuzumab ozogamicin for advanced disease. Previous treatments included front-line all-trans retinoic acid and anthracyclines, polychemotherapy consolidation, salvage chemotherapy for the first relapse followed by autologous stem cell transplantation (ASCT), arsenic trioxide for the second relapse followed by a second ASCT and then high-dose methotrexate for more advanced systemic disease with central nervous system involvement. The patient achieved prolonged haematological and molecular remission after monotherapy with gemtuzumab ozogamicin given at the time of the third relapse.

Effect of natural allergen exposure on non-specific bronchial reactivity in asthmatic farmers.

The aim of the study was to assess the seasonal variability of non-specific bronchial reactivity (NSBR) evaluated with methacholine in asthmatic farmers allergic to pollens. Twenty farmers (16 male and four female) with allergy to pollens, e.g. 'Graminae' and 'Parietaria', entered the study. None of the patients had been previously treated with specific immunotherapy. Patients underwent a methacholine challenge at the first visit and then in the subsequent seasons. Four groups of tests were obtained according to the period when the challenge was performed. Group 1: challenges performed in December, January and February; group 2 in March, April and May; group 3 in June, July and August; group 4 in September, October and November. PD20 values were expressed as the natural logarithm of the cumulative dose of methacholine causing at least a 20% fall in FEV1. Bronchial hyperreactivity was highest in summer, followed by spring and autumn; in winter it was much lower. Multiple group analysis (ANOVA) showed statistically significant differences between the groups (P < 0.01). When the groups were compared individually, statistically significant differences existed only between group 1 (winter) and each of the other groups, respectively 2 (spring) (P = 0.02), 3 (summer) (P = 0.004) and 4 (autumn) (P = 0.02). The results underlined the importance of allergic inflammation in determining changes in NSBR. In the region where the study was carried out (central Italy), the grass and Paretaria pollination lasts from March to November. Therefore, farmers had a progressive increase in NSBR from spring to summer and a decrease in fall as a consequence of the varying pollen concentration in different seasons. The level of allergen exposure is, in fact, the main factor that determines the severity of bronchial inflammation, thus affecting NSBR.

Prevalence of sensitization to Cupressus sempervirens: a 4-year retrospective study.

In the last few years Cupressus sempervirens has been identified as the cause of an increasing number of cases of late winter-early spring pollinosis in Mediterranean countries. We conducted a 4-year retrospective study of a large group of subjects with documented allergic respiratory disease in order to determine the prevalence, clinical significance and annual rate of sensitization to C. sempervirens pollen. Anamnestic data and skin prick tests (SPT) with common aeroallergens and C. sempervirens extract were collected from 1397 subjects (712 male and 685 female) resident in Latium, a region in central Italy, with complaints related to upper- or lower-respiratory-tract disorders or conjunctival disease. Two hundred and forty-three subjects (17.4%) showed positive results to C. sempervirens extract: 47 (19.3%) of them were monosensitized. The annual sensitization rate of SPT positivity to C. sempervirens varied from 7.2% in 1995 to 22% in 1998. All the subjects monosensitized to cypress pollen had symptoms from January through April. Our study suggests that sensitivity to C. sempervirens is responsible for respiratory symptoms in an increasing percentage of subjects. Further studies are needed to determine its frequency at the national level.

Bioactive constituents of Conyza albida.

The bioactivity-guided fractionation of an active chloroform extract of Conyza albida led to the isolation of three alkenynes, deca-4,6-diyn-2-(Z)-enoic methyl ester (1), deca-4,6-diyn-2-(Z)-enoic ethyl ester (2) and deca-2,4-diene-4-hydroxy-6-yn-1,4-olide (3), and the terpenoid spathulenol (4), as the active toxic metabolites in the Artemia sp. lethality test. When tested in the KB cell cytotoxicity assay, compounds 1-4 demonstrated IC50 values of 52.2, 38.4, 117.9, and 83.8 microM, respectively. All compounds studied were inactive in the DNA methyl green and DNA strand scission assays, while compounds 3 and 4 showed moderate activity as inhibitors of human topoisomerase I. Compound 2 is reported here for the first time.

Cytotoxic 4-nerolidylcatechol from Pothomorphe peltata inhibits topoisomerase I activity.

Bioactivity-guided fractionation of the leaf methanolic extract of P. peltata (Piperaceae), using the brine shrimp lethality test, led to the isolation of catechol derivative 4-nerolidylcatechol (4-NC). The methanolic extract was active against crown gall tumour in potato discs, showing a 22% crown gall tumour inhibition (SD = 4%), while 4-NC was cytotoxic against KB tumour cells growth (EC50 = 1.3 micrograms/ml). No interaction with DNA could be observed when tested using the methyl green-DNA (MG-DNA) bioassay. An inhibition in the activity of topoisomerase I using agarose gel electrophoresis was detected in the presence of the purified compound (IC50 = 20 micrograms/ml), suggesting that this could be a possible mechanism for the cytotoxicity observed in KB cells.

Prenatal cocaine exposure: long-term deficits in learning and motor performance.

We have developed a rabbit model of in utero exposure to intravenous injections of cocaine given twice daily to dams from gestational days 8-29. At the doses employed (4 mg/kg, injected twice daily), no differences were found in the body weight gain of dams, time to delivery, litter size, and body weight or other physical characteristics of the offspring. However, cocaine-exposed pups displayed an abnormal structural and neurochemical development of the anterior cingulate cortex which persisted into adulthood. In agreement with the known functions of the anterior cingulate cortex, we found that adult, sexually mature rabbits, exposed to cocaine prenatally, demonstrate impairments in motor function, alterations in associative learning and severe impairments in discrimination learning. Moreover, the alterations in discrimination learning were interpreted to be due to deficits in attentional processes. Specifically, cocaine progeny preferentially attend to more salient stimuli even when these are not relevant to the task. Consequently they have difficulty in attending to less salient but relevant stimuli when more salient but irrelevant stimuli occur in the same context. We concluded that the learning deficits are a reflection of the morphologic and neurochemical abnormalities of the anterior cingulate cortex. Alterations in dopamine function of the caudate nucleus may also contribute to the deficits in motor performance.

Repetitive treatment with serotonin modifies protein synthesis and protein phosphorylation in the central nervous system of Hirudo medicinalis.

Serotonin (5HT) is the neurotransmitter involved in some forms of short-term memory in the leech. Behavioral experiments have demonstrated that long-term memory requires new protein synthesis. With the aim of studying the molecular mechanism underlying memory processes in the leech, we have analyzed the effect of 5HT on protein synthesis and protein phosphorylation. Segmental ganglia of the leech central nervous system have been labeled, proteins have been separated by two-dimensional-electrophoresis and labeled proteins detected by autoradiography. Our findings indicate that repetitive treatment with 5HT produces either the persistence of phosphorylation or changes in protein synthesis in several proteins.

Food-dependent exercise-induced anaphylaxis: report of two cases.

Exercise-induced anaphylaxis (EIAn) is a rare condition characterized by giant urticaria, angioedema and acute gastrointestinal symptoms that develops on exertion. In the most severe forms it may be associated with acute cardiorespiratory symptoms (laringeal stridor, wheezing), profound hypotension or syncope. In some individuals, EIAn characteristically occurs after a meal suggesting that the anaphylactic reaction is provoked by both exercise and ingestion of a foodstuff to which the patient has become sensitized. Two representative cases of severe food-dependent EIAn are described, which emphasize the need of performing a careful allergological evaluation in sportsmen with unexplained cardiovascular and/or respiratory symptoms during effort, especially when associated with other allergic manifestations and/or occurring in the post-prandial period.