Advanced Digitalis intoxication is a rare event, mainly associated with overdose in patients with Digitalis therapy. We report an unusual case of acute 'familiar' digitalis poisoning in three ...patients who had eaten potato dumplings flavoured with leaves of Borago officinalis L. unconsciously mixed with leaves of Digitalis purpurea L. A complicated clinical course with marked bradyarrhythmias was presented, with good evolution thanks to the use of digoxin-specific antibody Fab fragments. The theme of the domestic use of plants with medicinal effects has been treated and discussed.
The pharmacological outline of a novel and original antagonist at the human tachykinin NK
2 receptor is presented, namely MEN13510 (
N-
N′-bis-2-(1
H-indol-3-yl)-ethyl-
N,
...N′-bis-(3-thiomorpholin-4-yl-propyl)-phthalamide). MEN13510 retained nanomolar affinity for the human tachykinin NK
2 receptor (
K
i 6.4 nM), and micromolar affinity for the human tachykinin NK
1 and NK
3 receptors. A competitive antagonism is indicated by the Schild analysis (p
K
B 7.8, slope −
0.94) of concentration–response curves of NKA induced inositolphosphates accumulation in Chinese hamster ovary (CHO) cells expressing the human NK
2 receptor in the presence of MEN13510 (30–300 nM concentration range). The MEN13510 interaction with the human NK
2 receptor was evaluated by means of heterologous inhibition binding experiments, by using agonist and antagonist radioligands (
125INKA,
3Hnepadutant,
3Hsaredutant) at a series of mutant receptors having single aminoacidic substitutions of residues located in transmembrane (TM) segments 3, 4, 5, 6, and 7. MEN13510 affinity was not affected by the mutations in TM 3 and 4 (Q109A, F112A, T171A, C167G), and it was reduced by 10-fold at the I202F mutant, but not at the Y206A (TM4). Amongst the investigated mutants bearing the mutated residues in TM6 (F270A, Y266F, W263A) only F270A decreased the MEN13510 affinity by 7-fold. Even mutations in TM7 did reduce MEN13510 affinity by 32-fold (Y289T, but not Y289F) and 13-fold (F293A). Studied mutations represent the human tachykinin NK
2 receptor discriminants involved in the binding of previously reported peptidic and nonpeptidic antagonists, against which results obtained with MEN13510 are compared. Results indicate that the binding site of this antagonist is, at least in part, overlapping to that described for NKA or saredutant. Finally we show that MEN13510 retains nanomolar affinity for the recently discovered splice variant of the human tachykinin NK
2 receptor, namely β isoform, as it has been described for the nonpeptide antagonist saredutant.
This study demonstrates a decision-support framework for planning Green Infrastructure (GI) systems that maximize urban ecosystem services in Camden, NJ. Seven key ecosystem services are evaluated ...(urban agriculture expansion, combined sewer overflow reduction, heat island reduction, flooding reduction, capacity building/green jobs expansion, fitness expansion, and stress reduction), to produce a normalized value for each service for each drainage sub-basin within the city. Gaps in ecosystem services are then mapped and utilized to geographically prioritize different kinds of multifunctional GI. Conceptual designs are developed for four site typologies: parks, schools, vacant lots, and brownfield sites. For one demonstration site, additional analysis is presented on urban engagement, life cycle cost reduction, and new sources of funding. What results is an integrated, long-term vision where multifunctional GI systems can be readily customized to meet multiple needs within urban communities. This study provides a portable and replicable framework for leveraging the regulatory requirement to manage stormwater to meet broader urban revitalization goals, all through a decentralized network of green infrastructure assets.
Aims
Transoesophageal echocardiography (TEE) with contrast administration is still considered as the reference method for the detection of patent foramen ovale (PFO) with interatrial shunt, but it is ...a semi-invasive exam. The aim of the present study is to evaluate a role of two- and three-dimensional transthoracic echocardiography (TTE and R3DTE) as a diagnostic alternative to transcranial Doppler ultrasound (TCD) and TEE for detection of atrial right-to-left shunt.
Methods and results
Seventy-five patients with history of cerebrovascular events were subjected to four diagnostic examinations: TCD, TTE, R3DTE, and TEE, with bubble contrast. Bubbles in the left atrium within three cardiac cycles were considered diagnostic for PFO and later as a pulmonary shunt. Greater than 20 bubbles in the left atrium were considered a large shunt and <20 a small shunt. Every exam was read blinded to the results of the others. From the 75 enrolled patients, 62 (82.6%) patients showed right-to-left shunt with TEE; the results were also positive in 53 patients using TCD (70.6%), in 53 using R3DTE (70.6%), and in 55 using TTE (73.3%) (P = NS). There is a statistically significant superiority for TEE in the capacity of detecting shunts compared with TCD (P < 0.024), TTE (P < 0.018), and R3DTE (P < 0.018). The TEE presents a superior ability to recognize mild/moderate interatrial shunts respect to other exams (P = 0.003), without differences for shunts of high degree. In comparison to the TEE, the sensitivity is 89% for TTE, 88% for R3DTE, and 85% for TCD; the specificity is 100% for TTE and R3DTE, and 90% for TCD; the positive predictive value is 100% for TTE and R3DTE, and 98% for TCD; and the negative predictive value is 65% for TTE, 65% for R3DTE, and 53% for TCD. Considering only for mild/moderate shunts, the diagnostic accuracy is clearly inferior (sensitivity 63% for TTE, 58% for R3DTE, and 53% for TCD).
Conclusion
In this cohort of patients, TEE confirms the role of 'gold standard' exam for the detection of PFO; the non-invasive methods, and the TTE in particular, present a good diagnostic accuracy, but are inferior to the TEE because of the low negative predictive value and the non-optimal detection of small shunts. If the only purpose of TEE is the detection of significative interatrial shunt, TEE can be replaced by TTE. The R3DTE presents a good diagnostic accuracy, provides a better anatomical definition of the interatrial septum, and may have a role in this setting of patients, but does not add a lot to the TTE for the diagnosis.
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