Diaminobutyric acid: A tool for discriminating between carrier-mediated and non-carrier-mediated release of GABA from synaptosomes?

The carrier-mediated transport of GABA in rat brain synaptosomes was strongly and permanently inhibited byl-2,4-diaminobutyric acid (DAB). In order to discriminate between carrier-mediated and non-carrier-mediated release of [³H]GABA, synaptosomes prelabeled with 0.5 M [³H]GABA in the presence of 100 M DAB, or with 0.2 M [³H]GABA without DAB, were superfused in conditions stimulating the release of [³H]GABA. Only the release elicited by unlabeled GABA or DAB (by homo- and heteroexchange, respectively) was strongly inhibited in DAB-pretreated synaptosomes. The spontaneous release and the release induced by 56 mM KCl in the presence of CaCl₂, by the ionophore A23187, by ouabain, by lack of K⁺, or by purified black widow spider toxin were unaffected or only barely decreased in DAB-treated synaptosomes, and therefore do not seem to be mediated by the DAB-blocked GABA carrier.     

La fioritura di „Tulipa silvestris“ L. in rapporto alla nutrizione azotata

Many members of the Orchidaceae, the largest vascular plant family in Ecuador, are at risk of extinction. It was therefore considered important to establish an efficient way of clonal propagation based on somatic embryogenesis of Cattleya maxima, a native Ecuadorian orchid. To this end, we evaluated the effect on somatic embryo induction of 12 combinations of 2,4-dichlorophenoxyacetic acid and 1-phenyl-3-(1,2,3-thiadiazol-5-yl)-urea, as well as three kinds of stresses. Protocorms produced 42% of embryogenic calli on 1/2 Murashige and Skoog (1/2 MS) medium, compared to 96.3% when protocorms were stressed for 6 h with 0.3 M NaCl, followed by cultivation on 1/2 MS medium supplemented with 0.1 mg L^? 1 2,4-D. Our data demonstrated that the combination of either salt (0.3 M NaCl) or osmotic stress (0.4 M sorbitol) with subculture on 2,4-D (0.1 mg L^–1) medium significantly increases the percentage of protocorms with embryogenic callus. The number of embryos per embryogenic callus was not significantly different from that obtained after subculture in growth factor-free medium.     

Regulation of Inflammation by IL-17A and IL-17F Modulates Non-Alcoholic Fatty Liver Disease Pathogenesis

Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide. While it is well-accepted that inflammation is central to NAFLD pathogenesis, the immune pathway(s) orchestrating disease progression are poorly defined. Notably, IL-17RA signaling, via IL-17A, plays an important role in obesity-driven NAFLD pathogenesis. However, the role of the IL-17F, another IL-17RA ligand, in NAFLD pathogenesis has not been examined. Further, the cell types expressing IL-17RA and producing IL-17RA ligands in the pathogenesis of NAFLD have not been defined. Here, IL-17RA^-/-, IL-17A^-/-, IL-17F^-/- and wild-type (WT) mice were fed either standard chow diet or methionine and choline deficient diet (MCDD)—a diet known to induce steatosis and hepatic inflammation through beta-oxidation dysfunction—and hepatic inflammation and NAFLD progression were subsequently quantified. MCDD feeding augmented hepatic IL-17RA expression and significantly increased hepatic infiltration of macrophages and IL-17A and IL-17F producing CD4⁺ and CD8⁺ T cells in WT mice. In contrast, IL-17RA^-/-, IL-17A^-/-, and IL-17F^-/- mice, despite increased steatosis, exhibited significant protection from hepatocellular damage compared to WT controls. Protection from hepatocellular damage correlated with decreased levels of hepatic T-cell and macrophage infiltration and decreased expression of inflammatory mediators associated with NAFLD. In sum, our results indicate that the IL-17 axis also plays a role in a MCDD-induced model of NAFLD pathogenesis. Further, we show for the first time that IL-17F, and not only IL-17A, plays an important role in NAFLD driven inflammation.     

Outcomes associated with planned place of birth among women with low-risk pregnancies

Background:Previous studies have shown that planned home birth is associated with a decreased likelihood of intrapartum intervention with no difference in neonatal outcomes compared with planned hospital birth. The purpose of our study was to evaluate different birth settings by comparing neonatal mortality, morbidity and rates of birth interventions between planned home and planned hospital births in Ontario, Canada.Methods:We used a provincial database of all midwifery-booked pregnancies between 2006 and 2009 to compare women who planned home birth at the onset of labour to a matched cohort of women with low-risk pregnancies who had planned hospital births attended by midwives. We conducted subgroup analyses by parity. Our primary outcome was stillbirth, neonatal death (< 28 d) or serious morbidity (Apgar score < 4 at 5 min or resuscitation with positive pressure ventilation and cardiac compressions).Results:We compared 11 493 planned home births and 11 493 planned hospital births. The risk of our primary outcome did not differ significantly by planned place of birth (relative risk [RR] 1.03, 95% confidence interval [CI] 0.68–1.55). These findings held true for both nulliparous (RR 1.04, 95% CI 0.62–1.73) and multiparous women (RR 1.00, 95% CI 0.49–2.05). All intrapartum interventions were lower among planned home births.Interpretation:Compared with planned hospital birth, planned home birth attended by midwives in a jurisdiction where home birth is well-integrated into the health care system was not associated with a difference in serious adverse neonatal outcomes but was associated with fewer intrapartum interventions.In Ontario, Canada, the College of Midwives of Ontario has regulated midwifery since 1994, and increasing numbers of women with low obstetrical risk and their newborns receive care in a publicly funded, midwifery-led continuity of care model.¹ Midwives have admission and discharge privileges at their local hospitals and are able to consult or transfer care to other health care providers if required. In Ontario, midwives attend a small proportion of all births in the province (10%), and about 20% of the births they attend take place at home.² A comprehensive record is maintained for every woman and infant in a midwife’s care. Until 2009, this record was submitted to the provincial Ministry of Health and Long-term Care (MOHLTC) through the Ontario Midwifery Program to access reimbursement for care provided.In the last century, Western culture has come to view hospital birth as safer than home birth.³ Recently, however, the value of hospital birth for all women with low-risk pregnancies has come into question; it has been suggested that in the absence of benefit, a planned hospital birth for this population may increase the use of intrapartum interventions, including cesarean delivery.^4–7 Even though recent studies comparing planned home and hospital births have had moderate sample sizes, they are individually limited in their ability to report definitively on rare outcomes such as death. Owing to a lack of evidence from randomized controlled trials (RCTs) to show that restricting a woman’s freedom to choose a place of birth prevents harm, the authors of a 2012 Cochrane review of planned hospital versus planned home births concluded that home birth services with collaborative medical backup should be established and offered to women with low-risk pregnancies in all jurisdictions.⁸ This conclusion, along with findings from the large English Birthplace Cohort Study,⁴ may be what prompted the National Institute for Health and Care Excellence (NICE) in England to update its intrapartum care guidelines to recommend that, for women at low risk of birth-associated complications, home birth should be considered a generally safe option.⁹ With the paucity of information derived from RCTs,⁸ observational studies are essential to continue to inform and monitor maternal and infant outcomes for women at low obstetrical risk who plan home or hospital birth, and to continue to provide pregnant women with quality information about choice of birthplace.The primary purpose of this retrospective cohort study was to determine the risk of stillbirth or neonatal death or serious neonatal morbidity among women at low obstetrical risk whose deliveries were attended by midwives and who had planned a home birth at the onset of labour, compared with women at low obstetrical risk who planned a hospital birth at the onset of labour. In addition, we also compared the incidence of maternal death and morbidity, birth interventions and breastfeeding between planned home births and planned hospital births.     

Pathophysiology of ageing, longevity and age related diseases

On April 18, 2007 an international meeting on Pathophysiology of Ageing, Longevity and Age-Related Diseases was held in Palermo, Italy. Several interesting topics on Cancer, Immunosenescence, Age-related inflammatory diseases and longevity were discussed. In this report we summarize the most important issues. However, ageing must be considered an unavoidable end point of the life history of each individual, nevertheless the increasing knowledge on ageing mechanisms, allows envisaging many different strategies to cope with, and delay it. So, a better understanding of pathophysiology of ageing and age-related disease is essential for giving everybody a reasonable chance for living a long and enjoyable final part of the life.     

Involvement of tubulin in MPP+ neurotoxicity on NGF-differentiated PC12 cells.

In vivo, the neurotoxin MPTP is oxidated to MPP⁺, which is toxic to dopaminergic neurons. In this paper, we have used MPP⁺ as a tool to evoke neurotoxicity in the PC12 cell line and investigate the intracellular events that are involved. A cytotoxicity test, performed on undifferentiated and NGF-differentiated PC12 cells, showed that MPP⁺ is much more toxic on differentiated cells and indicated the suitable range of concentrations for studying the starting events evoked by the neurotoxin. By indirect immunofluorescence we have shown that the localisation of α - and β -tubulin in NGF-differentiated cells was modified by a 24 h treatment with 15 μmol/l MPP⁺. A biochemical analysis was performed on cell extracts and the results showed that MPP⁺ treatment induced an increase in α -tubulin levels and a decrease in β -tubulin levels. These results suggest the involvement of the two microtubule proteins in MPP⁺ neurotoxicity on NGF-differentiated PC12 cells.     

Sublethal maternal pre-exposure of fish to cadmium. Effect on the survival of the newly hatched alevins

The aim of this study was to determine the effects of the exposure of pregnant females of a viviparous teleost Cnesterodon decemmaculatus to sublethal Cd solutions on the survival of their offspring. Ovigerous females were acclimated and accomodated in aquaria containing the following solutions: artificial freshwater medium (AFW) and AFW with 25, 50 and 100 microg Cd(2+) /L (as chloride). Part of the offspring born from control females was transferred to media contain-ing 25, 50 and 100 microg/L of cadmium; the rest of the fry stayed in AFW solutions without cadmium. The offspring born from the females maintained in solutions of cadmium were transferred to aquaria with AFW, and to solutions containing metal at the same concentration as their mother. In all cases mortality was recorded daily for 168 h. The results demonstrated that the survival of newborn offspring was always related to the concentration of Cd(2+) to which they were exposed at birth, regardless of the concentration of the metal to which the mother was exposed during its pregnancy. When exposed to Cd(2+), alevins from non-exposed females showed a constant linear death rate while in those from Cd-exposed it resulted exponential.     

3-Amino derivative of beta-cyclodextrin: thermodynamics of copper(II) complexes and exploitation of its enantioselectivity in the separation of amino acid racemates by ligand exchange capillary electrophoresis

The systems that the 3-amino derivative of beta-cyclodextrin (CD3NH2) forms with the proton, the copper(II) ion and each of the enantiomers of certain amino acids (alanine, phenylalanine, tyrosine and tryptophan) were investigated. The enantioselectivity shown by the potentiometric measurements carried out on the phenylalanine ternary systems was exploited in capillary electrophoresis by ligand exchange capillary electrophoresis (LECE) to obtain the separation of phenylalanine racemate. The tyrosine racemate was also separated by LECE. The comparison between thermodynamic and capillary electrophoresis (CE) results is discussed, in order to get a better insight into the separation mechanism.