OBJECTIVETo investigate the mechanism of ATP-sensitive potassium channel (K(ATP)) activator cromakalim (CRK) on action potentials and transient inward current (I(ti)) in isolated guinea pig papillary and ventricular myocytes and to explore the mechanisms of effects of I(ti) and K(ATP) treatment in idiopathic ventricular tachycardia.

METHODSThe whole-cell patch clamp recording technique was used to detect the action potentials and I(ti) and K(ATP) current alterations during the stimulated and triggered activity. Myocytes were isolated from guinea pig ventricle by enzyme digestion. The experiment was divided into four groups: (1) Control; (2) Control + Ouabain; (3) Control + CRK; (4) Control + Ouabain + CRK. (5) Control + Ouabain + CRK + glibenclamide (GLB). The action potential of guinea pig papillary muscles was measured by using standard microelectrode. The parameters in the experiment included the amplitude (APA), resting potentials (RP), action potentials duration (APD), as well as maximum rise of the action potential (Vmax).

RESULTS(1) When the guinea pig ventricular papillary myocytes were pretreated with Ouabain 0.5 micromol/L, APD prolonged significantly, especially APD(20), APD(50), APD(90). Delayed after depolorazion (DAD) and triggered activity were elicited. I(ti) currents and DAD as well as triggered activity increased. I(ti) current was (126.9 +/- 10.8) pA, lagT (1173.0 +/- 70.9) ms (n = 10, P < 0.01). (2) When guinea pig ventricular myocytes were pretreated with CRK (10 micromol/L), APD was shortened and the amplitude of DAD was lowered. The coupling time in CRK group was significantly prolonged compared with Ouabain group (n = 10, P < 0.01). (3) CRK 50 micromol/L pretreatment of the ventricular myocytes led to an increase of K(ATP) up to (342 +/- 89) pA, which was statistically significant as compared with the control group (P < 0.01). ATP-sensitive potassium channel blocker glibenclamide (10 micromol/L) could antagonize the effects of CRK on APD and I(ti) currents.

CONCLUSIONCRK might reduce the toxic effect of Ouabain on cardiomyocytes, shorten APD, terminate DAD and trigger excitation, and have protective effect on cardiomyocytes. The effects of CRK, may be associated with the inhibiting I(ti) current and increasing K(ATP).

Action Potentials ; drug effects ; Animals ; Cromakalim ; pharmacology ; Guinea Pigs ; Heart Ventricles ; drug effects ; Myocytes, Cardiac ; drug effects ; physiology ; Patch-Clamp Techniques ; Potassium Channels, Inwardly Rectifying ; agonists

OBJECTIVETo evaluate the feasibility, toxicity and tumor control of intensity modulated radiation therapy (IMRT) for recurrent nasopharyngeal carcinoma.

METHODSFourty-nine patients (Karnofsky performance status (KPS) >or= 80) with local-regional recurrence in the nasopharynx were treated with full course IMRT. Three patients with cervical lymph node metastasis (N1 2 and N3 1) were further supplemented with 5 to 6 courses of chemotherapy (Cisplatin + 5-Fu) after IMRT.

RESULTSThe results of treatment plan showed that the mean dose of covering gross tumor volume (GTV) (D(95)) in the nasopharynx was 68.09 Gy and the mean volume of GTV (V(95)) receiving the 95% dose was 98.46%. The mean dose of GTV, clinical target volume CTV1 and CTV2 in the targets were 71.40 Gy, 63.63 Gy and 59.81 Gy. The median follow-up time was 9 months (range 3 to 16 months). The local-regional progression-free survival was 100% with local-regional residual disease in 3 (6.1%) cases but was complicated with nasopharyngeal mucosa necrosis in 14 (28.6%) cases after IMRT.

CONCLUSIONIntensity modulated radiation therapy, as a re-treatment option for recurrent nasopharyngeal carcinoma, is able to improve the tumor target coverage and spare the adjacent critical structures. As high dose IMRT can result in radio-necrosis of nasopharyngeal mucosa, the prescription dose of GTV should be suitably decreased to 60 - 65 Gy.

Adult ; Aged ; Carcinoma, Squamous Cell ; pathology ; radiotherapy ; Female ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Nasopharyngeal Neoplasms ; pathology ; radiotherapy ; Neoplasm Recurrence, Local ; radiotherapy ; Neoplasm Staging ; Radiation Injuries ; pathology ; Radiotherapy Dosage ; Radiotherapy Planning, Computer-Assisted ; Radiotherapy, Conformal ; methods

Background: Upadacitinib is an oral Janus kinase1 (JAK1)-selective inhibitor, which showed a quick and significant effect on patients with atopic dermatitis in several phase 3 clinical studies. Although, an increasing number of studies have reported data on the real-world efficacy and safety of upadacitinib for the treatment of atopic dermatitis, no studies have yet been published in Korea. Objective: We assessed the real-world efficacy and safety of upadacitinib for the treatment of atopic dermatitis in Korean patients. Methods: A total of 17 patients with atopic dermatitis who received 15 mg of oral upadacitinib everyday for 16 weeks, were included in this retrospective single-center study. Based on electronic medical records, the clinical characteristics, Eczema Area and Severity Index (EASI) score, and adverse events were investigated. Results: The mean EASI score was significantly reduced at 4 weeks of upadacitinib treatment (8.81±9.00) and gradually reduced at week 8 (5.70±7.38), week 12 (4.55±6.23), and week 16 (4.58±6.74) (p＜0.001). At week 16, 61.54%, 30.77%, and 15.38% of patients achieved EASI 75, EASI 90, and EASI 100 responses, respectively. There was no statistically significant difference between EASI 75 and EASI 90 by age or gender at week 16 (p＞0.05). A total of 13 people (76.5%) had adverse events, of which acne was the most common. In all patients, the symptoms were mild and self-limited, and no patient discontinued treatment. Conclusion Upadacitinib was effective and safe for Korean patients with atopic dermatitis in real-world clinical practice.