Clinical prognosis of isolated anterior cerebral artery territory infarction: a retrospective study.

BACKGROUND: Isolated anterior cerebral artery territory (ACA) infarction is a rare phenomenon, and is known to have distinctive clinical features. Little is known regarding the clinical prognosis of isolated ACA territory infarction with associated factors, and its impact on dwelling and job status. We investigated the short- and long-term outcomes of anterior cerebral artery (ACA) territory infarction, and the associated factors involved in the development of the distinctive symptoms. METHODS: This retrospective study in a prospective cohort of acute ischaemic stroke patients included consecutively enrolled patients with isolated ACA territory infarction. We investigated the functional status using the modified Rankin scale (mRS) score at discharge, three months' post-discharge, and one-year post-discharge. We also investigated the occlusion site of the ACA (proximal vs. distal); presence of distinctive symptoms of ACA territory infarction including behaviour changes, indifference, aphasia, and urinary incontinence; and the effect of these symptoms on dwelling and job status one year after discharge. RESULTS: Between April 2014 and March 2019, 47 patients with isolated ACA territory infarction were included. Twenty-nine patients (61.7 %) had good outcomes (mRS ≤ 2) at discharge; however, the mRS score increased at three months (40; 85.1 %, p < 0.001) and one year (41; 87.2 %) post-discharge. Occlusion of the ACA proximal segment was independently associated with the development of distinctive symptoms (adjusted odds ratio, 17.68; 95 % confidence interval: 2.55-122.56, p < 0.05). Twenty-one (48.8 %) patients with good outcomes at one year experienced a change in dwelling status and job loss; 20 (95.2 %) of them had distinctive ACA territory symptoms with proximal ACA occlusion. CONCLUSIONS: Short- and long-term outcomes of isolated ACA territory infarction were favourable. However, proximal segment occlusion was associated with the development of distinctive symptoms, possibly related to future dwelling and job status.

The definition and diagnosis of cold hypersensitivity in the hands and feet: Finding from the experts survey.

BACKGROUND: Cold hypersensitivity in the hands and feet (CHHF) is a symptom patients usually feel cold in their hands and feet, but not dealt with a disease in western medicine. However, it is often appealed by patients at a clinic of Korean medicine (KM), considered to be a sort of key diagnostic indicator, and actively treated by physicians. Nevertheless, there is no standardized diagnostic definition for CHHF. Therefore, we surveyed KM experts' opinions to address the clinical definition, diagnostic criteria, and other relevant things on CHHF. METHODS: We developed a survey to assess the definition, diagnosis, causes, and accompanying symptoms on CHHF. 31 experts who work at specialized university hospitals affiliated with KM hospitals consented to participation. Experts responded to survey questions by selecting multiple-choice answers or stating their opinions. RESULTS: Vast majority of experts (83.8%) agreed with our definition on CHHF ("a feeling of cold as a symptom; that one's hands or feet become colder than those of average people in temperatures that are not normally perceived as cold"). 77.4% of experts considered subjective symptoms on CHHF were more important than medical instrument results. Constitution or genetic factors (87.1%) and stress (64.5%) were the most common causes reported for CHHF. CONCLUSIONS: This study offers an expert consensus regarding the themes, opinions, and experiences of practitioners with CHHF. Our results underscore the need for standardized definitions and diagnostic criteria for CHHF.

Quercetin potentiates apoptosis by inhibiting nuclear factor-kappaB signaling in H460 lung cancer cells.

The herbal flavonoid quercetin inhibits the growth of various cancer cells, but how it affects human cancer cells, particularly lung cancer cells, is unclear. We investigated the anticancer activity of quercetin and the underlying molecular mechanisms in non-small cell lung cancer (NSCLC) cells. Quercetin strongly inhibited cell proliferation, and increased sub-G1 and apoptotic cell populations regardless of p53 status. Quercetin-induced apoptosis was verified by caspase cleavage, Hoechst staining, trypan blue exclusion, and DNA fragmentation assays. Microarray analysis using H460 cells indicated that quercetin increased the expression of genes associated with death receptor signaling tumor necrosis factor-related apoptosis-inducing ligand receptor (TRAILR), caspase-10, interleukin (IL) 1R DNA fragmentation faotor 45 (DFF45), tumor necrosis factor receptor (TNFR) 1, FAS, inhibitor of kappaBalpha (IκBα)) and cell cycle inhibition growth arrest and DNA-damage inducible 45 (GADD45), p21(Cip1)), but decreased the expression of genes involved in nuclear factor (NF)-kappaB activation (NF-κB, IKKα). Further validation assays confirmed that quercetin inhibited growth by suppressing NF-κB and by increasing the expression of death receptors and cell cycle inhibitors. Taken together, these findings suggest that quercetin may be useful in the prevention and therapy of NSCLC.

c-Jun NH2-terminal kinase contributes to dexmedetomidine-induced contraction in isolated rat aortic smooth muscle.

PURPOSE: Dexmedetomidine, a full agonist of α2B-adrenoceptors, is used for analgesia and sedation in the intensive care units. Dexmedetomidine produces an initial transient hypertension due to the activation of post-junctional α2B-adrenoceptors on vascular smooth muscle cells (SMCs). The aims of this in vitro study were to identify mitogen-activated protein kinase (MAPK) isoforms that are primarily involved in full, α2B-adrenoceptor agonist, dexmedetomidine-induced contraction of isolated rat aortic SMCs. MATERIALS AND METHODS: Rat thoracic aortic rings without endothelium were isolated and suspended for isometric tension recording. Cumulative dexmedetomidine (10⁻9 to 10⁻6 M) dose-response curves were generated in the presence or absence of extracellular signal-regulated kinase (ERK) inhibitor PD 98059, p38 MAPK inhibitor SB 203580, c-Jun NH2-terminal kinase (JNK) inhibitor SP 600125, L-type calcium channel blocker (verapamil and nifedipine), and α2-adrenoceptor inhibitor atipamezole. Dexmedetomidine-induced phosphorylation of ERK, JNK, and p38 MAPK in rat aortic SMCs was detected using Western blotting. RESULTS: SP 600125 (10⁻6 to 10⁻5 M) attenuated dexmedetomidine-evoked contraction in a concentration- dependent manner, whereas PD 98059 had no effect on dexmedetomidine- induced contraction. SB 203580 (10⁻5 M) attenuated dexmedetomidine-induced contraction. Dexmedetomidine-evoked contractions were both abolished by atipamezole and attenuated by verapamil and nifedipine. Dexmedetomidine induced phosphorylation of JNK and p38 MAPK in rat aortic SMCs, but did not induce phosphorylation of ERK. CONCLUSION: Dexmedetomidine-induced contraction involves a JNK- and p38 MAPK-mediated pathway downstream of α2-adrenoceptor stimulation in rat aortic SMCs. In addition, dexmedetomidine-induced contractions are primarily dependent on calcium influx via L-type calcium channels.

The direct effect of levobupivacaine in isolated rat aorta involves lipoxygenase pathway activation and endothelial nitric oxide release.

BACKGROUND: Levobupivacaine is a long-acting local anesthetic with a clinical profile similar to that of racemic bupivacaine but with a greater margin of safety. Levobupivacaine produces dose-dependent vasoconstriction in vivo. Our goal in this in vitro study was to investigate the role of pathways involved in arachidonic acid metabolism in the levobupivacaine-induced contraction of isolated rat aorta and to determine which endothelium-derived vasodilators are involved in the modulation of levobupivacaine-induced contraction. METHODS: Rat thoracic aortic rings were isolated and suspended for isometric tension recording. Cumulative levobupivacaine dose-response curves over a range of 10(-6) to 3 x 10(-4) M were constructed in 1) aortic rings with no drug pretreatment; 2) endothelium-denuded rings pretreated with quinacrine dihydrochloride (nonspecific phospholipase A(2) inhibitor: 2 x 10(-5), 4 x 10(-5) M), nordihydroguaiaretic acid (NDGA) (lipoxygenase inhibitor: 10(-5), 3 x 10(-5) M), indomethacin (nonspecific cyclooxygenase inhibitor: 10(-5) M), AA-861 (5-lipoxygenase inhibitor: 10(-5), 5 x 10(-5) M), fluconazole (cytochrome P450 epoxygenase inhibitor: 10(-5) M), verapamil (10(-5) M), or calcium-free solution; and 3) endothelium-intact rings pretreated with N(omega)-nitro-L-arginine methyl ester (L-NAME) (nitric oxide synthase inhibitor: 5 x 10(-5) M), indomethacin, or fluconazole. Levobupivacaine-induced contractile response at each concentration (10(-4), 3 x 10(-4) M) was assessed in endothelium-denuded rings. Dose-response curves for potassium chloride in endothelium-denuded rings were generated in the presence or absence of NDGA and AA-861. Intracellular Ca(2+) levels were monitored by Ca(2+) image analysis using Fluo-4 fluorescence in vascular smooth muscle cells treated with levobupivacaine alone or AA-861 plus levobupivacaine. RESULTS: Levobupivacaine produced a tonic contraction in isolated rat aorta rings; this response was maximal at 10(-4) M levobupivacaine and gradually attenuated at 3 x 10(-4) M levobupivacaine. Levobupivacaine-induced contractions of endothelium-denuded rings were larger than those of endothelium-intact rings. Levobupivacaine-induced contraction of endothelium-denuded rings was attenuated by quinacrine dihydrochloride, NDGA, AA-861, verapamil, and calcium-free solution and, to a lesser extent, by indomethacin. L-NAME enhanced levobupivacaine-induced contraction of endothelium-intact rings and indomethacin slightly attenuated this contraction. NDGA and AA-861 attenuated the potassium chloride-induced contraction. AA-861 attenuated the levobupivacaine-induced intracellular calcium increase in vascular smooth muscle cells. CONCLUSIONS: Our data indicate that levobupivacaine-induced contraction of rat aortic smooth muscle is mediated mainly by activation of the lipoxygenase pathway and in part by activation of the cyclooxygenase pathway. In addition, activation of the lipoxygenase pathway seems to facilitate calcium influx via L-type calcium channels. Endothelial nitric oxide attenuates levobupivacaine-induced contraction.

Inhibitory effect of fentanyl on phenylephrine-induced contraction of the rat aorta.

PURPOSE: Fentanyl was reported to inhibit the alpha(1)-adrenoceptor agonist-induced contraction. The goal of this in vitro study was to identify the alpha(1)-adrenoceptor subtype primarily involved in the fentanyl-induced attenuation of phenylephrine-induced contraction in isolated endothelium-denuded rat aorta. MATERIALS AND METHODS: Aortic rings were suspended in order to record isometric tension. Concentration-response curves for phenylephrine (10(-9) to 10(-5) M) were generated in the presence or absence of one of the following drugs: fentanyl (3 x 10(-7), 10(-6), 3 x10(-6) M), 5-methylurapidil (3 x10(-8), 10(-7), 3 x 10(-7) M), chloroethylclonidine (10(-5) M) and BMY 7378 (3 x 10(-9), 10(-8), 3 x 10(-8) M). Phenylephrine concentration-response curves were generated in the presence or absence of fentanyl in rings pretreated with either 3 x10(-9) M prazosin, 10(-9) M 5-methylurapidil or 3 x 10(-9) M BMY 7378. RESULTS: Fentanyl (10(-6), 3 x 10(-6) M) attenuated phenylephrine-induced contraction in the rat aorta. 5-Methylurapidil and BMY 7378 produced a parallel rightward shift in the phenylephrine concentration-response curve. The pA(2) values for 5-methylurapidil and BMY 7378 were estimated to be 7.71 +/- 0.15 and 8.99 +/- 0.24, respectively. Fentanyl (10(-6) M) attenuated phenylephrine-induced contraction in rings pretreated with 10(-9) M 5-methylurapidil, but did not alter the rings when pretreated with 3 x 10(-9) M BMY 7378. Pretreatment of the rings with chloroethylclonidine showed a 72.9 +/- 2.3% reduction in phenylephrine-induced maximal contraction. CONCLUSION: The results suggest that fentanyl attenuates phenylephrine-induced contraction by inhibiting the pathway involved in the alpha(1D)-adrenoceptor-mediated contraction of the rat aorta.

Direct effect of dexmedetomidine on rat isolated aorta involves endothelial nitric oxide synthesis and activation of the lipoxygenase pathway.

1. The aims of the present in vitro study were to examine the roles of pathways associated with arachidonic acid metabolism in dexmedetomidine-induced contraction and to determine which endothelium-derived vasodilators are involved in the endothelium-dependent attenuation of vasoconstriction elicited by dexmedetomidine. 2. Dexmedetomidine (10(-9)-10(-6) mol/L) concentration-response curves were constructed in: (i) aortic rings with no drug pretreatment; (ii) endothelium-denuded aortic rings pretreated with either 2 x 10(-5) mol/L quinacrine dihydrochloride, 10(-5) mol/L nordihydroguaiaretic acid (NDGA), 3 x 10(-5) mol/L indomethacin or 10(-5) mol/L fluconazole; and (iii) endothelium-intact aortic rings pretreated with either 5 x 10(-5) mol/L N(G)-nitro-l-arginine methyl ester (l-NAME), 10(-5) mol/L fluconazole, 10(-5) mol/L indomethacin, 10(-5) mol/L glibenclamide, 5 x 10(-3) mol/L tetraethylammonium or 5 x 10(-5) mol/L l-NAME plus rauwolscine (10(-5), 10(-6) mol/L). The production of nitric oxide (NO) metabolites was determined in human umbilical vein endothelial cells treated with dexmedetomidine. 3. Quinacrine dihydrochloride, NDGA and indomethacin attenuated the dexmedetomidine-induced contraction of endothelium-denuded rings. Dexmedetomidine (10(-7)-10(-6) mol/L)-induced contractions of endothelium-denuded rings were enhanced compared with those of endothelium-intact rings, as were dexmedetomidine-induced contractions of endothelium-intact rings pretreated with l-NAME or tetraethylammonium. Rauwolscine attenuated dexmedetomidine-induced contractions in endothelium-intact rings pretreated with l-NAME. Dexmedetomidine (10(-6) mol/L) was found to activate NO production. 4. Taken together, the results indicate that dexmedetomidine-induced contraction of aortic rings involves activation of the lipoxygenase and cyclo-oxygenase pathways and is attenuated by increased NO production following stimulation of endothelial alpha(2)-adrenoceptors by dexmedetomidine.