Daily requirement of softgel thyroxine is independent from gastric juice pH

BackgroundSoftgel levothyroxine (LT4) preparation showed a better in vitro dissolution profile at increasing pH as compared to tablet LT4 preparation. Clinical studies suggested a better performance of softgel LT4 preparation in patients with gastric disorders but whether this finding is related to gastric juice pH variation in vivo is not known. MethodsTwenty-eight hypothyroid patients (24F/4M; median age=50 treated with tablet LT4 (median dose= 1.65 mu g/kg/day) and with stable thyroid stimulating hormone (TSH) values on target ( mU/l) have been shifted to softgel LT4 preparation. The dose of softgel LT4 has been titrated to obtain a similar individual serum TSH value. All subjects followed a specific treatment schedule, taking LT4 in fasting condition and then abstaining from eating or drinking for at least 1 hour. Owing to the presence of long-lasting dyspepsia or of already known gastric disorders, all patients underwent endoscopy, upon informed consent. Gastric juice has been collected during endoscopy to measure gastric pH. Then we plotted the dose of LT4 with the gastric pH obtained in vivo, before and after the switch tablet/softgel preparation in all patients. ResultsUpon the switch tablet/softgel preparation, the therapeutic LT4 dose was very slightly reduced (-6%) in the whole sample. However, the individual variations revealed the existence of two populations, one without any dose reduction (A) and the other showing a dose reduction >20% (B). Upon matching with the actual gastric pH, patients with normal pH (A: n=17; 14F/3M, median 1.52) no showed a lower softgel LT4 requirement. Instead, among patients with reduced gastric acid production (B: n=11; 10F/1M, median pH 5.02) the vast majority (10/11; 91%, p<0.0001) benefited from a lower dose of softgel LT4 (median = -23%, p<0.0001). Interestingly, the dose of LT4 in tablet correlated with pH value (Spearman's rho =0.6409; p = 0.0002) while softgel dose was independent from gastric juice pH (Spearman's rho =1.952; p = 0.3194). ConclusionsThese findings provide evidence that softgel LT4 preparation is independent from the actual gastric pH in humans and may represent a significant therapeutic option in patients with increased LT4 requirement, owed to disorders impairing the gastric acidic output

Lactobacillus rhamnosus GG supplementation on eradication rate and dyspepsia in Helicobacter pylori infection treated with three-in-one bismuth quadruple therapy

IntroductionHelicobacter pylori (Hp)-related dyspepsia has been related to gastroduodenal dysbiosis. The role of probiotic supplementation in the clinical management of Hp infection has been the object of several studies in terms of improvement of efficacy and tolerability of eradication treatments but data on their effects on the outcomes of post-eradication dyspepsia are lacking. The aim of the present study was to evaluate the influence of Lactobacillus rhamnosus GG (LGG) supplementation on bismuth quadruple therapy (BQT) in the clinical management of Hp-related infection both in terms of efficacy and tolerability and persistence of post-treatment dyspepsia.MethodsA total of 164 (121 women) Hp-positive adult patients were enrolled in this pilot study and assigned to two different treatment regimens: group A received BQT for 10 days (three capsules qid, IPP bid) and group B received BQT for 10 days in combination with 6 × 109CFU LGG (ATCC53103) taken for 24 days (7 days before, 10 days during, and 7 days after therapy). Eradication was assessed after 45 days using the 13C-urea breath test (13C-UBT). Dyspepsia, distinguished into postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS), was assessed at the time of enrollment and 6 months after eradication.ResultsApproximately 98 patients were enrolled in group A and 66 patients in group B. At the enrollment, dyspepsia was present in 76.5% of group A and 86.5% of group B. No significant differences were observed in eradication rate between the 2 groups, both in intention-to-treat (ITT) analysis (82.3 vs. 75.0%) and per-protocol (PP) analysis (95 vs. 96%), and in the presence of side effects during the treatment (70.6 vs. 65.4%). At 6 months after eradication of Hp infection, the persistence of dyspepsia was statistically higher in patients of group A than in group B (38.8 vs. 16.1%; p = 0.032). The positive influence of LGG supplementation in improving post-eradication dyspepsia resulted in statistically more effectiveness in PDS dyspepsia, whose remission was 41.7% in group A and 84% in group B patients (p = 0.011).ConclusionIn conclusion, LGG supplementation during Hp eradication therapy, even if not affecting eradication rates and therapy-related side effects, significantly impacts the remission of dyspepsia

Different Antioxidant Efficacy of Two MnII-Containing Superoxide Anion Scavengers on Hypoxia/Reoxygenation-Exposed Cardiac Muscle Cells

Oxidative stress due to excess superoxide anion ([Formula: see text]) produced by dysfunctional mitochondria is a key pathogenic event of aging and ischemia-reperfusion diseases. Here, a new [Formula: see text]-scavenging MnII complex with a new polyamino-polycarboxylate macrocycle (4,10-dimethyl-1,4,7,10-tetraazacyclododecane-1,7-diacetate) containing 2 quinoline units (MnQ2), designed to improve complex stability and cell permeability, was compared to parental MnII complex with methyls replacing quinolines (MnM2). MnQ2 was more stable than MnM2 (log K = 19.56(8) vs. 14.73(2) for the equilibrium Mn2+ + L2-, where L = Q2 and M2) due to the involvement of quinoline in metal binding and to the hydrophobic features of the ligand which improve metal desolvation upon complexation. As oxidative stress model, H9c2 rat cardiomyoblasts were subjected to hypoxia-reoxygenation. MnQ2 and MnM2 (10 μmol L-1) were added at reoxygenation for 1 or 2 h. The more lipophilic MnQ2 showed more rapid cell and mitochondrial penetration than MnM2. Both MnQ2 and MnM2 abated endogenous ROS and mitochondrial [Formula: see text], decreased cell lipid peroxidation, reduced mitochondrial dysfunction, in terms of efficiency of the respiratory chain and preservation of membrane potential (Δψ) and permeability, decreased the activation of pro-apoptotic caspases 9 and 3, and increased cell viability. Of note, MnQ2 was more effective than MnM2 to exert cytoprotective anti-oxidant effects in the short term. Compounds with redox-inert ZnII replacing the functional MnII were ineffective. This study provides clues which further our understanding of the structure-activity relationships of MnII-chelates and suggests that MnII-polyamino-polycarboxylate macrocycles could be developed as new anti-oxidant drugs

Evidence for heavy fuel oil combustion aerosols from chemical analyses at the island of Lampedusa: a possible large role of ships emissions in the Mediterranean

Measurements of aerosol chemical composition made on the island of Lampedusa, south of the Sicily channel, during years 2004–2008, are used to identify the influence of heavy fuel oil (HFO) combustion emissions on aerosol particles in the Central Mediterranean. Aerosol samples influenced by HFO are characterized by elevated Ni and V soluble fraction (about 80% for aerosol from HFO combustion, versus about 40% for crustal particles), high V and Ni to Si ratios, and values of V<sub>sol</sub>>6 ng m<sup>−3</sup>. Evidence of HFO combustion influence is found in 17% of the daily samples. Back trajectories analysis on the selected events show that air masses prevalently come from the Sicily channel region, where an intense ship traffic occurs. This behavior suggests that single fixed sources like refineries are not the main responsible for the elevated V and Ni events, which are probably mainly due to ships emissions. <br><br> V<sub>sol</sub>, Ni<sub>sol</sub>, and non-sea salt SO<sub>4</sub><sup>2−</sup> (nssSO<sub>4</sub><sup>2−</sup>) show a marked seasonal behaviour, with an evident summer maximum. Such a pattern can be explained by several processes: (i) increased photochemical activity in summer, leading to a faster production of secondary aerosols, mainly nssSO<sub>4</sub><sup>2−</sup>, from the oxidation of SO<sub>2</sub> (ii) stronger marine boundary layer (MBL) stability in summer, leading to higher concentration of emitted compounds in the lowest atmospheric layers. A very intense event in spring 2008 was studied in detail, also using size segregated chemical measurements. These data show that elements arising from heavy oil combustion (V, Ni, Al, Fe) are distributed in the sub-micrometric fraction of the aerosol, and the metals are present as free metals, carbonates, oxides hydrates or labile complex with organic ligands, so that they are dissolved in mild condition (HNO<sub>3</sub>, pH1.5). <br><br> Data suggest a characteristic nssSO<sub>4</sub><sup>2−</sup>/V ratio in the range 200–400 for HFO combustion aerosols in summer at Lampedusa. By using the value of 200 a lower limit for the HFO contribution to total sulphates is estimated. HFO combustion emissions account, as a summer average, at least for 1.2 μg m<sup>−3</sup>, representing about 30% of the total nssSO<sub>4</sub><sup>2−</sup>, 3.9% of PM<sub>10</sub>, 8% of PM<sub>2.5</sub>, and 11% of PM<sub>1</sub>. Within the used dataset, sulphate from HFO combustion emissions reached the peak value of 6.1 μg m<sup>−3</sup> on 26 June 2008, when it contributed by 47% to nssSO<sub>4</sub><sup>2−</sup>, and by 15% to PM<sub>10</sub>

Characterization of PM10 sources in the central Mediterranean

The Mediterranean Basin atmosphere is influenced by both strong natural and anthropogenic aerosol emissions and is also subject to important climatic forcings. Several programs have addressed the study of the Mediterranean basin; nevertheless important pieces of information are still missing. In this framework, PM10 samples were collected on a daily basis on the island of Lampedusa (35.5° N, 12.6° E; 45 m a.s.l.), which is far from continental pollution sources (the nearest coast, in Tunisia, is more than 100 km away). After mass gravimetric measurements, different portions of the samples were analyzed to determine the ionic content by ion chromatography (IC), the soluble metals by inductively coupled plasma atomic emission spectrometry (ICP-AES), and the total (soluble + insoluble) elemental composition by particle-induced x-ray emission (PIXE). Data from 2007 and 2008 are used in this study. The Positive Matrix Factorization (PMF) model was applied to the 2-year long data set of PM10 mass concentration and chemical composition to assess the aerosol sources affecting the central Mediterranean basin. Seven sources were resolved: sea salt, mineral dust, biogenic emissions, primary particulate ship emissions, secondary sulfate, secondary nitrate, and combustion emissions. Source contributions to the total PM10 mass were estimated to be about 40 % for sea salt, around 25 % for mineral dust, 10 % each for secondary nitrate and secondary sulfate, and 5 % each for primary particulate ship emissions, biogenic emissions, and combustion emissions. Large variations in absolute and relative contributions are found and appear to depend on the season and on transport episodes. In addition, the secondary sulfate due to ship emissions was estimated and found to contribute by about one-third to the total sulfate mass. Results for the sea-salt and mineral dust sources were compared with estimates of the same contributions obtained from independent approaches, leading to an estimate of the water content bound to the sea salt in the marine source

Constraining the ship contribution to the aerosol of the Central Mediterranean

Abstract. Particulate matter with aerodynamic diameters lower than 10 µm, (PM10) aerosol samples were collected during summer 2013 within the framework of the Chemistry and Aerosol Mediterranean Experiment (ChArMEx) at two sites located north (Capo Granitola) and south (Lampedusa Island), respectively, of the main Mediterranean shipping route in the Straight of Sicily. The PM10 samples were collected with 12 h time resolutions at both sites. Selected metals, main anions, cations and elemental and organic carbon were determined. The evolution of soluble V and Ni concentrations (typical markers of heavy fuel oil combustion) was related to meteorology and ship traffic intensity in the Straight of Sicily, using a high-resolution regional model for calculation of back trajectories. Elevated concentration of V and Ni at Capo Granitola and Lampedusa are found to correspond with air masses from the Straight of Sicily and coincidences between trajectories and positions of large ships; the vertical structure of the planetary boundary layer also appears to play a role, with high V values associated with strong inversions and a stable boundary layer. The V concentration was generally lower at Lampedusa than at Capo Granitola V, where it reached a peak value of 40 ng m−3. Concentrations of rare earth elements (REEs), La and Ce in particular, were used to identify possible contributions from refineries, whose emissions are also characterized by elevated V and Ni amounts; refinery emissions are expected to display high La ∕ Ce and La ∕ V ratios due to the use of La in the fluid catalytic converter systems. In general, low La ∕ Ce and La ∕ V ratios were observed in the PM samples. The combination of the analyses based on chemical markers, air mass trajectories and ship routes allows us to unambiguously identify the large role of the ship source in the Straight of Sicily. Based on the sampled aerosols, ratios of the main aerosol species arising from ship emission with respect to V were estimated with the aim of deriving a lower limit for the total ship contribution to PM10. The estimated minimum ship emission contributions to PM10 were 2.0 µg m−3 at Lampedusa and 3.0 µg m−3 at Capo Granitola, corresponding with 11 and 8.6 % of PM10, respectively

Ulcerative Colitis as a Novel Cause of Increased Need for Levothyroxine

Background: Thyroxine absorption takes place at the small intestine level and several disorders affecting this intestinal tract lead to thyroxine malabsorption. An increased need for thyroxine has also been observed in gastric disorders due to variations in drug dissolution and/or in its ionization status. Ulcerative colitis (UC) is an inflammatory bowel disease that has been postulated as a potential cause of the increased need for thyroxine, but there is a lack of evidence on this topic. This study is aimed at measuring the thyroxine requirement in hypothyroid patients with UC.Patients and Methods: Among 8,573 patients with thyroid disorders consecutively seen in our referral center from 2010 to 2017, we identified 34 patients with a definite diagnosis of UC. Thirteen of them were hypothyroid (12 F/1 M; median age = 53 years), bearing UC during the remission phase and in need for thyroxine treatment, thus representing the study group. The dose of T4 required by UC patients has been compared to the one observed in 51 similarly treated age- and weight-matched patients, compliant with treatment and clearly devoid of any gastrointestinal and /or pharmacological interference.Results: To reach the target serum TSH, the dose of thyroxine had to be increased in twelve out of thirteen (92%) hypothyroid patients with ulcerative colitis. The median thyroxine dose required by UC patients was 1.54 μg/kg weight/day, that is 26% higher than the control patients, to reach a similar TSH (1.23 μg/kg weight/day; p = 0.0002). Since half of our study group consisted of patients aged over 60 years old, we analyzed the effect of age on the subdivision in two classes. Six out of seven (86%) adult patients (<60 years) required more T4 than those in the respective control group (1.61 vs. 1.27 μg/kg weight/day; +27%; p < 0.0001). An increased dose (+17%; p = 0.0026) but to a lesser extent, was also observed in all patients over 60 years, as compared to the control group.Conclusions: In almost all hypothyroid patients with UC, the therapeutic dose of thyroxine is increased. Therefore, ulcerative colitis, even during clinical remission, should be included among the gastrointestinal causes of an increased need for oral thyroxine

Elucidating the present-day chemical composition, seasonality and source regions of climate-relevant aerosols across the Arctic land surface

The Arctic is warming two to three times faster than the global average, and the role of aerosols is not well constrained. Aerosol number concentrations can be very low in remote environments, rendering local cloud radiative properties highly sensitive to available aerosol. The composition and sources of the climate-relevant aerosols, affecting Arctic cloud formation and altering their microphysics, remain largely elusive due to a lack of harmonized concurrent multi-component, multi-site, and multi-season observations. Here, we present a dataset on the overall chemical composition and seasonal variability of the Arctic total particulate matter (with a size cut at 10 mu m, PM10, or without any size cut) at eight observatories representing all Arctic sectors. Our holistic observational approach includes the Russian Arctic, a significant emission source area with less dedicated aerosol monitoring, and extends beyond the more traditionally studied summer period and black carbon/sulfate or fine-mode pollutants. The major airborne Arctic PM components in terms of dry mass are sea salt, secondary (non-sea-salt, nss) sulfate, and organic aerosol (OA), with minor contributions from elemental carbon (EC) and ammonium. We observe substantial spatiotemporal variability in component ratios, such as EC/OA, ammonium/nss-sulfate and OA/nss-sulfate, and fractional contributions to PM. When combined with component-specific back-trajectory analysis to identify marine or terrestrial origins, as well as the companion study by Moschos et al 2022 Nat. Geosci. focusing on OA, the composition analysis provides policy-guiding observational insights into sector-based differences in natural and anthropogenic Arctic aerosol sources. In this regard, we first reveal major source regions of inner-Arctic sea salt, biogenic sulfate, and natural organics, and highlight an underappreciated wintertime source of primary carbonaceous aerosols (EC and OA) in West Siberia, potentially associated with the oil and gas sector. The presented dataset can assist in reducing uncertainties in modelling pan-Arctic aerosol-climate interactions, as the major contributors to yearly aerosol mass can be constrained. These models can then be used to predict the future evolution of individual inner-Arctic atmospheric PM components in light of current and emerging pollution mitigation measures and improved region-specific emission inventories.Peer reviewe