GABA shunt enzymes and the relationship with morphine abstinence

Selective inhibition of tbe rate-limiting step in tbe degradation of tbe inhibitory neurotransmitter Y·aminobutyric acid (GABA) might be of potential use in the treatment of many neurological or psychiatric disorders since it might correct a central GABA deficiency. Alternatively, as such diseases have not been correlated convincingly witb changes in tbe GABA-ergic system, inhibition of this rate-limiting step by specific drugs in clinical trials could be useful in demonstrating tbe existence of a GABA deficiency in tbese disturbances. The study of effects of drugs exerting a tberapeutic action in specific neurological or psychiatric disorders on the rate-limiting enzyme in GABA degradation might also be useful. Therefore, tbe primary object of tbis tbesis has been to find the rate-limiting step in GABA degradation. GABA is degraded by tbe consecutive action of two enzymes: GABA-transaminase and SSA-dehydrogenase. It is almost generally believed tbat GABA-transaminase is rate-limiting in GABA degradation. As a consequence, SSA-dehydrogenase has been almost completely ignored as a likely candidate for a regulatory function in tbe GABA ·shunt. Based on in vitro experiments it is suggested in this tbesis that SSA-dehydrogenase may have a regulatory function in the GABA shunt. To test this hypothesis in vivo it became of crucial importance to fmd a behavioural correlate of increased GABA-ergic activity in tbe rat. Such a behavioural correlate might be the increased locomotor activity and quasi-morphine abstinence behaviour observed after administration of di·n-propylacetate (DPA) to tbe rat. This drug is used in the treatment of petit mal epilepsy (SIMON & PENRY, 1975) and probably acts via inhibition of SSA-dehydrogenase (HARVEY et al, 1975; ANLEZARK et al., 1976). The special character of tbe behaviour observed after administration of DPA suggests tbat an increased GABA-ergic activity might be related to the well known morphine abstinence syndrome. Therefore, some studies have been conducted witb morphine to demonstrate this relationship. In addition, this DPA-induced abstinence behaviour has been studied pharmacologically to demonstrate its relationship witb an overactive GABA-ergic system in vivo

Tire-road noise: an experimental study of tire and road design parameters

It is widely known that road traffic noise has negative influences on human health. Hence, as tire-road noise is considered to be the most dominant cause of road traffic noise above 30-50 km/h, a lot of research is performed by the two involving industries: road authorities/manufacturers and tire manufacturers. Usually, the parameters influencing exterior tire-road noise are often examined separately, whereas it is the tire-road interaction which obviously causes the actual noise. An integral approach, i.e. assessing possible measures to reduce tire-road noise from both the road and the tire point of view, is needed to further reduce traffic noise. In a project Silent Safe Traffic, this tire-road interaction is studied in more detail without focusing on either tire or road but looking at the tire-road system. In this publication we present experimental results of tire and road design parameters influencing tire-road noise from a fixed reference tire-road configuration. The influence of tire tread pattern, compound and construction as well as the influence of road roughness, acoustic absorption and driving speed on the exterior tire-road noise, measured by a CPX-set up, is reported. Keywords: Tire, Road, Measuremen

Identification of Risk Factors for Dupilumab-associated OculaSurface Disease in Patients with Atopic Dermatitis

This study identified risk factors for the development of dupilumab-associated ocular surface disease in patients with moderate-to-severe atopic dermatitis in a large prospective daily practice cohort. Data from the Dutch BioDay Registry were used to assess the risk of developing dupilumab-associated ocular surface di-sease, by performing univariate and multivariate logistic regression analyses. A total of 469 patients were included, of which 152/469 (32.4%) developed dupi-lumab-associated ocular surface disease. Multivariate analysis showed a statistically significant association of the development of dupilumab-associated ocular surface disease with a history of any eye disease (his-tory of self-reported episodic acute allergic conjunctivitis excluded) combined with the use of ophthalmic medication at the start of dupilumab (odds ratio 5.16, 95% confidence interval 2.30–11.56, p < 0.001). In conclusion, a history of any eye disease (history of self-reported episodic acute allergic conjunctivitis ex-cluded) combined with the use of ophthalmic medication at baseline was associated with the development of dupilumab-associated ocular surface disease in patients with atopic dermatitis

Recent geospatial dynamics of Terceira (Azores, Portugal) and the theoretical implications for the biogeography of active volcanic islands

Ongoing work shows that species richness patterns on volcanic oceanic islands are shaped by surface area changes driven by longer time scale (>1 ka) geological processes and natural sea level fluctuations. A key question is: what are the rates and magnitudes of the forces driving spatial changes on volcanic oceanic islands which in turn affect evolutionary and biogeographic processes? We quantified the rates of surface-area changes of a whole island resulting from both volcanogenic flows and sea level change over the last glacial-interglacial (GI) cycle (120 ka) for the volcanically active island of Terceira, (Azores, Macaronesia, Portugal). Volcanogenic activity led to incidental but long-lasting surface area expansions by the formation of a new volcanic cone and lava-deltas, whereas sea level changes led to both contractions and expansions of area. The total surface area of Terceira decreased by as much as 24% per time step due to changing sea levels and increased by 37% per time step due to volcanism per time step of 10 ka. However, while sea levels nearly continuously changed the total surface area, volcanic activity only impacted total surface area during two time steps over the past 120 ka. The surface area of the coastal and lowland region (here defined as area <300 m) was affected by sea level change (average change of 11% / 10 ka for 120–0 ka) and intra-volcanic change (average change of 17% / 10 ka for 120–0 ka). We discuss the biogeographic implications of the quantified dynamics, and we argue that surface area change is mainly driven by volcanic processes in the early stages of the island’s life cycle, while during the later stages, area change becomes increasingly affected by sea level dynamics. Both environmental processes may therefore affect biota differently during the life cycle of volcanic oceanic islands.S.J.N. received funding from the Portuguese National Funds, through Fundação para a Ciência e a Tecnologia (FCT), within the project UID/BIA/00329/2013 and the Research Fellowship PD/BD/114380/2016. S.P.A. acknowledges his research contract (IF/00465/2015) funded by the Portuguese Science Foundation (FCT). C.S.M. is benefiting from a PhD grant M3.1.a/F/100/2015 from FRCT/Açores 2020 by Fundo Regional para a Ciência e Tecnologia (FRCT). Financial support to R.A. was received from the Laboratory of Excellence ‘TULIP’ (PIA-10-LABX-41). This work was supported by FEDER funds through the Operational Programme for Competitiveness Factors – COMPETE and by National Funds through FCT under the UID/BIA/50027/2013, POCI-01-0145-FEDER-006821 and under DRCT-M1.1.a/005/Funcionamento-C-/2016 (CIBIO-A) project from FRCT. This work was also supported by FEDER funds (in 85%) and by funds of the Regional Government of the Azores (15%) through Programa Operacional Açores 2020, in the scope of the project “AZORESBIOPORTAL – PORBIOTA”: ACORES‑01‑0145-FEDER-000072.info:eu-repo/semantics/publishedVersio

Health outcomes of 1000 children born to mothers with inflammatory bowel disease in their first 5 years of life

OBJECTIVE: The aim of this study was to describe the long-term health outcomes of children born to mothers with inflammatory bowel disease (IBD) and to assess the impact of maternal IBD medication use on these outcomes. DESIGN: We performed a multicentre retrospective study in The Netherlands. Women with IBD who gave birth between 1999 and 2018 were enrolled from 20 participating hospitals. Information regarding disease characteristics, medication use, lifestyle, pregnancy outcomes and long-term health outcomes of children was retrieved from mothers and medical charts. After consent of both parents, outcomes until 5 years were also collected from general practitioners. Our primary aim was to assess infection rate and our secondary aims were to assess adverse reactions to vaccinations, growth, autoimmune diseases and malignancies. RESULTS: We included 1000 children born to 626 mothers (381 (61%) Crohn's disease, 225 (36%) ulcerative colitis and 20 (3%) IBD unclassified). In total, 196 (20%) had intrauterine exposure to anti-tumour necrosis factor-α (anti-TNF-α) (60 with concomitant thiopurine) and 240 (24%) were exposed to thiopurine monotherapy. The 564 children (56%) not exposed to anti-TNF-α and/or thiopurine served as control group. There was no association between adverse long-term health outcomes and in utero exposure to IBD treatment. We did find an increased rate of intrahepatic cholestasis of pregnancy (ICP) in case thiopurine was used during the pregnancy without affecting birth outcomes and long-term health outcomes of children. All outcomes correspond with the general age-adjusted population. CONCLUSION: In our study, we found no association between in utero exposure to anti-TNF-α and/or thiopurine and the long-term outcomes antibiotic-treated infections, severe infections needing hospital admission, adverse reactions to vaccinations, growth failure, autoimmune diseases and malignancies

Efficacy of serology driven “test and treat strategy” for eradication of H. pylori in patients with rheumatic disease in the Netherlands

The treatment of choice of H. pylori infections is a 7-day triple-therapy with a proton pump inhibitor (PPI) plus amoxicillin and either clarithromycin or metronidazole, depending on local antibiotic resistance rates. The data on efficacy of eradication therapy in a group of rheumatology patients on long-term NSAID therapy are reported here. This study was part of a nationwide, multicenter RCT that took place in 2000–2002 in the Netherlands. Patients who tested positive for H. pylori IgG antibodies were included and randomly assigned to either eradication PPI-triple therapy or placebo. After completion, follow-up at 3 months was done by endoscopy and biopsies were sent for culture and histology. In the eradication group 13% (20/152, 95% CI 9–20%) and in the placebo group 79% (123/155, 95% CI 72–85%) of the patients were H. pylori positive by histology or culture. H. pylori was successfully eradicated in 91% of the patients who were fully compliant to therapy, compared to 50% of those who were not (difference of 41%; 95% CI 18–63%). Resistance percentages found in isolates of the placebo group were: 4% to clarithromycin, 19% to metronidazole, 1% to amoxicillin and 2% to tetracycline