Behcet's disease is a multisystemic vasculitis. Arterial involvement in the form of acute dissection is rare. A 42-year-old Lebanese man with Behcet's disease presented with severe abdominal pain. On exam, blood pressure was 162/104 mm Hg, and he exhibited epigastric tenderness. CT angiogram demonstrated an acute dissection of the coeliac artery trunk, common hepatic artery and proper hepatic arteries, with asymmetric thickening of the proximal left subclavian artery and circumferential thickening of the abdominal infrarenal aorta suggestive of vasculitis. Treatment included intravenous clevidipine, nitroprusside and methylprednisolone, which transitioned to oral metoprolol, amlodipine and prednisone. He responded well. Arterial dissections have been described with Behcet's. We report a coeliac artery aneurysm in association with a flare of Behcet's disease. Arterial wall inflammation combined with the sheering forces of hypertension likely predisposes to arterial dissection.

Chromatographic methods are progressing continuously. Increasing sample complexity and safety expectations lead to higher regulatory demands, hence challenges in liquid chromatography analysis are rising, even today, when faster and faster chromatographic systems are extensively employed and become widely accessible for successful method development. The goal of this study was to investigate the impact of mobile phase influences as important factors of selectivity tuning in method development. This would mitigate mobile phase-related robustness issues throughout the method's lifecycle. To discover and understand these effects, a new module of chromatographic modeling software DryLab (ver. 4.3.4. beta) was introduced and a special experimental design (DoE) was tested, allowing the simultaneous optimization of solvent-dependent parameters, such as gradient time (tG), ternary eluent composition (tC) and pH, requiring 18 input experiments (2 × 3 × 3 = 18). Additionally, the model creation, using a UPLC system and a narrow bore column (50×), the entire experimental work could be finished in 2-3 hours. To demonstrate the applicability of this new design, amlodipine and its related pharmacopoeia impurities (A-H) were subjected to be used in a case study. Predicted vs. Experimental (or Verification) runs showed excellent agreement, average retention time deviations were typically less than 1 s. Modelled robustness testing was also performed, elucidating all important mobile phase and instrument parameters that could influence a method's lifetime performance. Furthermore, as the in silico robustness testing is the least time consuming part of the method development process, it can be used extensively to evaluate robustness even at the very early part in stage 1 of the Method Life Cycle (MLC).

We screened a library of botanical compounds purified from plants of Vietnam for modulators of the activity of a two-pore domain K+ channel, TREK-1, and we identified a hydroxycoumarin-related compound, ostruthin, as an activator of this channel. Ostruthin increased whole-cell TREK-1 channel currents in 293T cells at a low concentration (EC50 = 5.3 μM), and also activity of the TREK-2 channel (EC50 = 3.7 mM). In contrast, ostruthin inhibited other K+ channels, e.g. human ether-à-go-go-related gene (HERG1), inward-rectifier (Kir2.1), voltage-gated (Kv1.4), and two-pore domain (TASK-1) at higher concentrations, without affecting voltage-gated potassium channel (KCNQ1 and 3). We tested the effect of this compound on mouse anxiety- and depression-like behaviors and found anxiolytic activity in the open-field, elevated plus maze, and light/dark box tests. Of note, ostruthin also showed antidepressive effects in the forced swim and tail suspension tests, although previous studies reported that inhibition of TREK-1 channels resulted in an antidepressive effect. The anxiolytic and antidepressive effect was diminished by co-administration of a TREK-1 blocker, amlodipine, indicating the involvement of TREK-1 channels. Administration of ostruthin suppressed the stress-induced increase in anti-c-Fos immunoreactivity in the lateral septum, without affecting immunoreactivity in other mood disorder-related nuclei, e.g. the amygdala, paraventricular nuclei, and dorsal raphe nucleus. Ostruthin may exert its anxiolytic and antidepressive effects through a different mechanism from current drugs.

Historically, traditional herbal medicines (THMs) have been the conventional treatment strategy in the Korean medical system for treating many diseases. However, THMs have rarely been used to treat hypertension, and moreover few studies have investigated the interaction of blood pressure with the coadministration of synthetic antihypertensives. We aimed to evaluate the vasorelaxant and hypotensive effects of the traditional herbal prescription Cheonwangbosimdan (CWBSD; "Tianwangbuxindan" in Chinese) and the combination of CWBSD with amlodipine. CWBSD was extracted with distilled water at 100°C for 2 h. To investigate vasorelaxant activities, CWBSD with amlodipine (10 μg/ml) was added cumulatively (10-1,000 μg/ml) to isolated rat aortic rings precontracted using phenylephrine or potassium chloride in organ chambers. To investigate hypotensive effects, CWBSD (2,476 mg/kg) was orally administered with or without amlodipine (5 mg/kg) to spontaneously hypertensive rats (SHRs). CWBSD increased the relaxation of rat aortic rings induced by amlodipine (P < 0.01). In vivo, CWBSD coadministration with amlodipine also significantly decreased the blood pressure of SHRs compared to the amlodipine-treated group. These results suggested that CWBSD could be a useful herbal prescription to treat hypertension and we recommend establishing guidelines for the use of herbal medicines in conjunction with antihypertensive drugs, including amlodipine.

Increasing numbers of elderly people require multi-drug therapies. One route to improve adherence rates is to prepare fixed dose combinations (FDCs), in which multiple active ingredients are loaded into a single formulation. Here, we report the use of electrospinning to prepare fast-dissolving oral FDCs containing amlodipine besylate and valsartan, two drugs prescribed as FDCs for the treatment of hypertension. Electrospun fibers were prepared loaded with one or both drugs, using polyvinylpyrrolidone as the polymer matrix. The fibers were cylindrical in morphology and comprise amorphous solid dispersions except with the highest loadings of amlodipine besylate. HPLC demonstrated drug entrapment efficiencies of between 90 and 99% of the theoretical dose. The mats have folding endurances and thicknesses suitable for use as oral films. The amlodipine besylate-loaded systems are fast-dissolving, with 100% release obtained within 120 s. In contrast, valsartan release from its single-drug formulations took longer, ranging from 360 s to 24 min. With the FDC formulations, rapid release within 360 s was achieved when the loading was 5% w/w of each drug, but again the release time increased with drug loading. Electrospun fibers therefore have significant promise as FDCs, but the target drug and its loading need to be carefully considered.