Stevens-Johnson Syndrome and Herpes Simplex Type 1 Infection during Adalimumab Therapy for Crohn's Disease

Stevens–Johnson syndrome (SJS) is a severe mucocutaneous adverse drug reaction with a relatively high mortality rate. SJS is described during herpes simplex virus type 1 (HSV1) infection and, rarely, even during adalimumab therapy. We report the case of a patient with Crohn’s disease who developed SJS during an HSV1 infection and a contemporaneous anti-TNFα therapy with adalimumab. Remission was achieved with suspension of adalimumab and high doses of intravenous steroids and antivirals. Patients with HSV1 infection and on adalimumab therapy have a combined risk of SJS and should be monitored closely

Visceral sensitivity modulation by faecal microbiota transplantation: the active role of gut bacteria in pain persistence

Recent findings linked gastrointestinal disorders characterized by abdominal pain to gut microbiota composition. The present work aimed to evaluate the power of gut microbiota as a visceral pain modulator and, consequently, the relevance of its manipulation as a therapeutic option in reversing postinflammatory visceral pain persistence. Colitis was induced in mice by intrarectally injecting 2,4-dinitrobenzenesulfonic acid (DNBS). The effect of faecal microbiota transplantation from viscerally hypersensitive DNBS-treated and naive donors was evaluated in control rats after an antibiotic-mediated microbiota depletion. Faecal microbiota transplantation from DNBS donors induced a long-lasting visceral hypersensitivity in control rats. Pain threshold trend correlated with major modifications in the composition of gut microbiota and short chain fatty acids. By contrast, no significant alterations of colon histology, permeability, and monoamines levels were detected. Finally, by manipulating the gut microbiota of DNBS-treated animals, a counteraction of persistent visceral pain was achieved. The present results provide novel insights into the relationship between intestinal microbiota and visceral hypersensitivity, highlighting the therapeutic potential of microbiota-targeted interventions

VOLCANISM AND INTRUSIONS OF THE DECCAN TRAPS, INDIA: GEOCHEMISTRY AND GEOCHRONOLOGY OF THE MAGMATIC ROCKS AND PALEOENVIRONMENTAL CONSEQUENCES

The Deccan Traps are one of the most important Large Igneous Provinces (LIP) in the world, they are mainly constituted by tholeiitic lava flows, now covering almost one sixth of the Indian continent, and reaching the maximum exposed thickness of 1300 m. The emplacement of such quantities of magma and its timing (ca. 66Ma) close to the Cretaceous-Paleogene (K-Pg) boundary, have led several authors to propose a causal link between the formation of the province and the K-Pg boundary mass extinction . Moreover, a distinctive feature of the province is the presence, beside the tholeiites, of several alkaline bodies, associated with the main fault zones of India. These two important aspects of the Deccan Traps have been investigated in the northern portion of the province by sampling both alkaline and tholeiitic rocks, in order to provide precise timing of emplacement and to constrain the relationship between them through the definition of their mantle source. 40Ar/39Ar step-heating analyses provided two different age peaks that straddle the K-Pg boundary, one with an age comparable with the main phase of Deccan volcanism (ca 66.5 Ma), the other slightly younger (ca. 65.2 Ma), thus confirming the synchrony between the emplacement of the province and the end-Cretaceous mass extinction. Therefore, the input in the atmosphere of huge quantities of gas, produced by the emplacement of the Deccan Traps, could have contributed to the extinction. In particular a crucial role may be provided in this sense by the alkaline magmas, which are likely enriched in volatile elements. Whole rock analyses showed that the samples span a wide compositional range varying from little-evolved compositions such as picro-basalts to fairly evolved ones such as rhyolite; the large variation is observed in the total alkali content (Na2O+K2O) as well, ranging from the subalakaline basalt field, up to strongly alkaline samples like phonolites. Alkaline rocks appear enriched in the most incompatible elements and present higher La/Yb ratios (19.5-68.8). They are also characterized by negative K anomaly (possibly suggesting the presence of a K-rich residual mantle mineral), and Pb spikes; on average they present patterns similar to those displayed by other alkaline rocks of the Deccan Traps, thus suggesting analogous origin and source. Sr-Nd isotopes define a large spectrum of compositions, departing from a similar depleted end-member (εNdt ca. +3 and 87Sr/86Srt ca. 0.705) and trending towards low εNdt and relatively low 87Sr/86Srt (-12.96 and 0.71061, respectively), and toward very high 87Sr/86Srt (0.72788) and low εNdt (-12.50). The trend with higher 87Sr/86Srt has been interpreted as the result of Assimilation- Fractional Crystallization (AFC) process, starting from a magma similar to Réunion OIBs or Central Indian Ridge basalts progressively contaminated by rocks from the Indian cratons (Dharwar and Aravalli cratons). The trend towards low εNdt and relatively low 87Sr/86Srt is defined mainly by mafic sulbalkaline rocks from the Phenai Mata intrusion. These rocks are characterized also by very high 207Pb/204Pbt and 208Pb/204Pbt ratios. Given the preliminary 187Os/188Ost compositions (0.1584 to 0.2457), mafic subalkaline rocks assimilated only negligible amounts of crust. Their enriched Sr-Nd-Pb isotopic composition is thus best interpreted as resulting from recycling of ancient sediments in their mantle source. On the contrary, alkaline samples present quite homogeneous isotopic compositions, slightly more enriched than that of nearby carbonatite complexes (e.g. Amba Dongar) and substantially more enriched than Reunion basalts. Therefore, the alkaline rocks are unlikey a product of the Reunion mantle plume, but more probably of the subcontinental lithospheric mantle, as is consistent also with their incompatible trace element contents and patterns.I Deccan Traps sono una delle più importanti grandi province magmatiche del mondo, sono principalmente costituiti da colate di lava tholeiitica, attualmente ricoprono circa un sesto del continente Indiano e raggiungono uno spessore massimo di 1300m. La messa in posto di queste grandi quantità di magma avvenuta al limite Cretaceo-Paleogene (K-Pg), ha portato diversi autori a proporre un rapporto di causalità tra la formazione di questa provincia e l’estinzione di massa al limite K-Pg. Inoltre, una caratteristica dei Deccan Traps è la presenza, oltre alle tholeiiti, di diversi corpi alcalini associati con le principali zone di faglia indiane. Questi due importanti aspetti dei Deccan traps sono stati studiati nella porzione nordoccidentale della provincia, campionando rocce alcaline e tholeiitiche, al fine di definire un preciso tempo di messa in posto e caratterizzare la relazione tra le diverse litologie, attraverso la determinazione della loro sorgente di mantello. Le analisi 40Ar/39Ar step-heating hanno restituito due diversi picchi di età a cavallo del limite K-Pg, il primo con un’età comparabile a quella della fase principale del magmatismo Deccan (ca. 66.5Ma), il secondo più giovane (ca. 65.2 Ma), confermando quindi l’effettiva sincronia tra la formazione della provincia e l’estinzione di massa alla fine del Cretaceo. Quindi, l’immissione in atmosfera di grandi quantità di gas, prodotta dalla messa in posto dei Deccan Traps, può aver contribuito all’estinzione. In particolare un ruolo molto importante potrebbe essere stato quello dei magmi alcalini, che verosimilmente sono arricchiti in elementi volatili. I campioni coprono un ampio range composizionale in termini di elementi maggiori, variando da composizioni poco evolute come i picro-basalti, a evolute come le rioliti; la variabilità è osservata anche nel contenuto di alcali (Na2O+K2O), variando dal campo subalcalino dei basalti a quello di campioni fortemente alcalini come le fonoliti. Le rocce alcaline sono arricchite negli elementi più incompatibili e presentano un rapporto La/Yb più alto (19.5-68.8). sono inoltre caratterizzate da una anomalia negativa in K, (probabilmente dovuta alla presenza di una fase residuale ricca in K nel mantello) e ad una positiva in Pb; in genere presentano pattern simili a quelli di altre rocce alcaline dei Deccan Traps, suggerendo quindi un’origine simile. Anche i rapporti isotopici di Sr e Nd definiscono un ampio range composizionale, partendo da un end-member impoverito (εNdt ca. +3 and 87Sr/86Srt ca. 0.705), verso composizioni a basso εNdt e relativamente basso 87Sr/86Srt (-12.96 and 0.71061, rispettivamente), e verso composizioni a 87Sr/86Srt (0.72788) molto alto e basso εNdt (-12.50). Il trend a più alto 87Sr/86Srt è stato interpretato come il risultato di un processo di assimilazione e cristallizzazione frazionata (AFC), a partire da un magma simile alle composizioni tipiche di Réunion o del Central Indian Ridge, progressivamente contaminato da rocce dei Cratoni indiani (Dharwar e Aravalli). Il trend verso composizioni a basso εNdt e relativamente basso 87Sr/86Srt è definito principalmente da rocce mafiche subalcaline dell’intrusione di Phenai Mata, queste rocce sono anche caratterizzate da rapporti 207Pb/204Pbt and 208Pb/204Pbt molto alti. Date le prime composizioni isotopiche 187Os/188Ost (da 0.1584 a 0.2457), queste rocce hanno assimilato porzioni trascurabili di crosta. Le loro composizioni Sr-Nd-Pb arricchite sono quindi meglio interpretate come il risultato del contributo nella sorgente di mantello di antichi sedimenti riciclati. Al contrario i campioni alcalini presentano composizioni isotopiche piuttosto omogene, leggermente più arricchite rispetto a quelle dei vicini complessi carbonatitici (p. es. Amba Dongar) e decisamente più arricchiti dei basalti di Réunion. Perciò le rocce alcaline sembrano non essere il prodotto del plume di Réunion, ma più probabilmente del mantello litosferico subcontinentale, come suggerito anche dai contenuti e dai pattern degli elementi in traccia

VOLCANISM AND INTRUSIONS OF THE DECCAN TRAPS, INDIA: GEOCHEMISTRY AND GEOCHRONOLOGY OF THE MAGMATIC ROCKS AND PALEOENVIRONMENTAL CONSEQUENCES

The Deccan Traps are one of the most important Large Igneous Provinces (LIP) in the world, they are mainly constituted by tholeiitic lava flows, now covering almost one sixth of the Indian continent, and reaching the maximum exposed thickness of 1300 m. The emplacement of such quantities of magma and its timing (ca. 66Ma) close to the Cretaceous-Paleogene (K-Pg) boundary, have led several authors to propose a causal link between the formation of the province and the K-Pg boundary mass extinction . Moreover, a distinctive feature of the province is the presence, beside the tholeiites, of several alkaline bodies, associated with the main fault zones of India. These two important aspects of the Deccan Traps have been investigated in the northern portion of the province by sampling both alkaline and tholeiitic rocks, in order to provide precise timing of emplacement and to constrain the relationship between them through the definition of their mantle source. 40Ar/39Ar step-heating analyses provided two different age peaks that straddle the K-Pg boundary, one with an age comparable with the main phase of Deccan volcanism (ca 66.5 Ma), the other slightly younger (ca. 65.2 Ma), thus confirming the synchrony between the emplacement of the province and the end-Cretaceous mass extinction. Therefore, the input in the atmosphere of huge quantities of gas, produced by the emplacement of the Deccan Traps, could have contributed to the extinction. In particular a crucial role may be provided in this sense by the alkaline magmas, which are likely enriched in volatile elements. Whole rock analyses showed that the samples span a wide compositional range varying from little-evolved compositions such as picro-basalts to fairly evolved ones such as rhyolite; the large variation is observed in the total alkali content (Na2O+K2O) as well, ranging from the subalakaline basalt field, up to strongly alkaline samples like phonolites. Alkaline rocks appear enriched in the most incompatible elements and present higher La/Yb ratios (19.5-68.8). They are also characterized by negative K anomaly (possibly suggesting the presence of a K-rich residual mantle mineral), and Pb spikes; on average they present patterns similar to those displayed by other alkaline rocks of the Deccan Traps, thus suggesting analogous origin and source. Sr-Nd isotopes define a large spectrum of compositions, departing from a similar depleted end-member (εNdt ca. +3 and 87Sr/86Srt ca. 0.705) and trending towards low εNdt and relatively low 87Sr/86Srt (-12.96 and 0.71061, respectively), and toward very high 87Sr/86Srt (0.72788) and low εNdt (-12.50). The trend with higher 87Sr/86Srt has been interpreted as the result of Assimilation- Fractional Crystallization (AFC) process, starting from a magma similar to Réunion OIBs or Central Indian Ridge basalts progressively contaminated by rocks from the Indian cratons (Dharwar and Aravalli cratons). The trend towards low εNdt and relatively low 87Sr/86Srt is defined mainly by mafic sulbalkaline rocks from the Phenai Mata intrusion. These rocks are characterized also by very high 207Pb/204Pbt and 208Pb/204Pbt ratios. Given the preliminary 187Os/188Ost compositions (0.1584 to 0.2457), mafic subalkaline rocks assimilated only negligible amounts of crust. Their enriched Sr-Nd-Pb isotopic composition is thus best interpreted as resulting from recycling of ancient sediments in their mantle source. On the contrary, alkaline samples present quite homogeneous isotopic compositions, slightly more enriched than that of nearby carbonatite complexes (e.g. Amba Dongar) and substantially more enriched than Reunion basalts. Therefore, the alkaline rocks are unlikey a product of the Reunion mantle plume, but more probably of the subcontinental lithospheric mantle, as is consistent also with their incompatible trace element contents and patterns.I Deccan Traps sono una delle più importanti grandi province magmatiche del mondo, sono principalmente costituiti da colate di lava tholeiitica, attualmente ricoprono circa un sesto del continente Indiano e raggiungono uno spessore massimo di 1300m. La messa in posto di queste grandi quantità di magma avvenuta al limite Cretaceo-Paleogene (K-Pg), ha portato diversi autori a proporre un rapporto di causalità tra la formazione di questa provincia e l’estinzione di massa al limite K-Pg. Inoltre, una caratteristica dei Deccan Traps è la presenza, oltre alle tholeiiti, di diversi corpi alcalini associati con le principali zone di faglia indiane. Questi due importanti aspetti dei Deccan traps sono stati studiati nella porzione nordoccidentale della provincia, campionando rocce alcaline e tholeiitiche, al fine di definire un preciso tempo di messa in posto e caratterizzare la relazione tra le diverse litologie, attraverso la determinazione della loro sorgente di mantello. Le analisi 40Ar/39Ar step-heating hanno restituito due diversi picchi di età a cavallo del limite K-Pg, il primo con un’età comparabile a quella della fase principale del magmatismo Deccan (ca. 66.5Ma), il secondo più giovane (ca. 65.2 Ma), confermando quindi l’effettiva sincronia tra la formazione della provincia e l’estinzione di massa alla fine del Cretaceo. Quindi, l’immissione in atmosfera di grandi quantità di gas, prodotta dalla messa in posto dei Deccan Traps, può aver contribuito all’estinzione. In particolare un ruolo molto importante potrebbe essere stato quello dei magmi alcalini, che verosimilmente sono arricchiti in elementi volatili. I campioni coprono un ampio range composizionale in termini di elementi maggiori, variando da composizioni poco evolute come i picro-basalti, a evolute come le rioliti; la variabilità è osservata anche nel contenuto di alcali (Na2O+K2O), variando dal campo subalcalino dei basalti a quello di campioni fortemente alcalini come le fonoliti. Le rocce alcaline sono arricchite negli elementi più incompatibili e presentano un rapporto La/Yb più alto (19.5-68.8). sono inoltre caratterizzate da una anomalia negativa in K, (probabilmente dovuta alla presenza di una fase residuale ricca in K nel mantello) e ad una positiva in Pb; in genere presentano pattern simili a quelli di altre rocce alcaline dei Deccan Traps, suggerendo quindi un’origine simile. Anche i rapporti isotopici di Sr e Nd definiscono un ampio range composizionale, partendo da un end-member impoverito (εNdt ca. +3 and 87Sr/86Srt ca. 0.705), verso composizioni a basso εNdt e relativamente basso 87Sr/86Srt (-12.96 and 0.71061, rispettivamente), e verso composizioni a 87Sr/86Srt (0.72788) molto alto e basso εNdt (-12.50). Il trend a più alto 87Sr/86Srt è stato interpretato come il risultato di un processo di assimilazione e cristallizzazione frazionata (AFC), a partire da un magma simile alle composizioni tipiche di Réunion o del Central Indian Ridge, progressivamente contaminato da rocce dei Cratoni indiani (Dharwar e Aravalli). Il trend verso composizioni a basso εNdt e relativamente basso 87Sr/86Srt è definito principalmente da rocce mafiche subalcaline dell’intrusione di Phenai Mata, queste rocce sono anche caratterizzate da rapporti 207Pb/204Pbt and 208Pb/204Pbt molto alti. Date le prime composizioni isotopiche 187Os/188Ost (da 0.1584 a 0.2457), queste rocce hanno assimilato porzioni trascurabili di crosta. Le loro composizioni Sr-Nd-Pb arricchite sono quindi meglio interpretate come il risultato del contributo nella sorgente di mantello di antichi sedimenti riciclati. Al contrario i campioni alcalini presentano composizioni isotopiche piuttosto omogene, leggermente più arricchite rispetto a quelle dei vicini complessi carbonatitici (p. es. Amba Dongar) e decisamente più arricchiti dei basalti di Réunion. Perciò le rocce alcaline sembrano non essere il prodotto del plume di Réunion, ma più probabilmente del mantello litosferico subcontinentale, come suggerito anche dai contenuti e dai pattern degli elementi in traccia

40Ar/39Ar ages of alkaline and tholeiitic rocks from the northern Deccan Traps: implications for magmatic processes and the K–Pg boundary

The Deccan large igneous province in India was emplaced temporally close to the Cretaceous–Palaeogene (K–Pg) boundary and is formed by tholeiitic flood basalts and less abundant alkaline rocks. Definition of the origin of Deccanmagmatism and of its environmental impact relies on precise and accurate geochronological analyses.We present new40Ar/39Ar ages from the northern sector of the province. In this area, tholeiitic and alkaline rocks were contemporaneously emplaced at 66.60 ± 0.35 to 65.25 ± 0.29 Ma in the Phenai Mata area, whereas rocks from Rajpipla and Mount Pavagadh yielded ages ranging from 66.40 ± 2.80 to 64.90 ± 0.80 Ma. The indistinguishable ages for alkaline and tholeiitic magmatism suggest that distinct mantle sources were synchronously active. The new ages are compared with previous ages, which were carefully screened and filtered and then recalculated to be comparable. The entire dataset of geochronological data does not support a time-related migration of the magmatismrelated to the northward Indian platemovement relative to the Reunion mantle plume. The main phase of magmatism, including the newly dated rocks from the northern Deccan, occurred at the K–Pg boundary. This suggests a causal link between the emplacement of the province and the K–Pg mass extinction

Effects of Ultramicronized <i>N</i>-Palmitoylethanolamine Supplementation on Tramadol and Oxycodone Analgesia and Tolerance Prevention

Chronic pain management requires increasing doses of opioids, the milestone of painkillers, which may result in the onset of tolerance with exacerbated side effects. Maintaining stable analgesia with low doses of opioids is thus imperative. N-palmitoylethanolamine (PEA) is an endogenous lipid compound endowed with pain-relieving as well as anti-inflammatory properties. The ultramicronized formulation of PEA was recently demonstrated to be able to modulate morphine’s effects, delaying tolerance and improving efficacy. To evaluate the possible application to other opioids, in this study, we analysed the capacity of ultramicronized PEA to regulate analgesia and tolerance induced by oxycodone and tramadol. Pre-emptive and continuative treatment with ultramicronized PEA (30 mg kg−1, daily, per os) delayed the onset of opioid tolerance and enhanced opioid analgesia when it was acutely administered in association with tramadol (20 mg kg−1, daily, subcutaneously) or oxycodone (0.5 mg kg−1, daily, subcutaneously). Moreover, PEA exerted antinociceptive effects on tolerant rats, suggesting the use of PEA together with opioids for stable, long-lasting analgesia. To that purpose, the oxycodone dose needed to be increased from 0.3 mg kg−1 (day 1) up to 1 mg kg−1 (day 31) in the oxycodone + vehicle group; the tramadol dose was progressively enhanced from 15 mg kg−1 to 50 mg kg−1 in 31 days in the tramadol + vehicle group. Acute oral co-treatment with PEA (120 mg kg−1) achieved the same analgesia without increasing the dose of both opioids. The behavioural effects of PEA on opioid chronic treatment paralleled a decrease in astrocyte activation in the dorsal horn of the spinal cord (a marker of the development of opioid tolerance) and with a modulation of mRNA expression of IL-6 and serpin-A3. In conclusion, pre- and co-administration of ultramicronized PEA delayed the development of tramadol tolerance, potentiating either oxycodone or tramadol analgesia and allowing a long-lasting analgesic effect with a low opioid dose regimen. The use of PEA is suggested for clinical purposes to support the opioid-based management of persistent pain

Increased Risk of Liver Cirrhosis during Azathioprine Therapy for Crohn&apos;s Disease

Azathioprine is a cornerstone of the therapy of Crohn’s disease. Unfortunately, infections and malignancies are relatively common adverse effects related to this drug; however, cirrhosis is exceptionally reported as a side effect. We report the case of a 49-year-old male patient with ileocolonic steno-penetrating Crohn’s disease who developed hepatic cirrhosis while treated with azathioprine. After taking azathioprine for 3 years with regular follow-up, he developed pancytopenia, and liver cirrhosis was diagnosed with ultrasound, abdomen computed tomography scan, transient elastography, and liver biopsy. As all other causes of liver damage were excluded, azathioprine was believed to be the cause of liver injury and therefore was interrupted