CD4+CD25high+regulatory T cells (Tregs) are considered to be of vital importance for maintaining immunologic self-tolerance and preventing autoimmune diseases. These cells have been found to be deficient in skin lesions and in the peripheral blood of patients with psoriasis.
To investigate the role of Tregs in the pathogenesis of psoriasis and to evaluate the changes in Tregs in relation to the severity and the clinical course of psoriasis.
Immunohistochemistry (CD3, 4, 8, 79 and FOXP3) was performed in 22 psoriatic patients compared to 5 normal controls. Flow cytometry (CD3, 4, 8, 25 and FOXP3) was performed in 18 psoriatic patients and 8 normal volunteers and reverse transcriptase polymerase chain reaction (foxp3 mRNA) was performed in 8 psoriasis patients.
An increase in the FOXP3+ cell fraction was detected in the lesional psoriatic skin irrespective of the severity of psoriasis as compared with the normal skin. However, a decrease in FOXP3+ cells was observed in the samples obtained from psoriasis of 'acute course'. FOXP3+ Treg populations in the blood of the 'acute course' psoriasis was not different compared to that of 'chronic course' psoriasis and normal controls.
The deficiency of FOXP3+ Tregs in the lesional psoriatic skin might be responsible for the exacerbation of psoriasis.
CD4+CD25high+regulatory T cells; FOXP3; Psoriasis
Dilated cardiomyopathy (DCM) is usually an idiopathic disease with a poor prognosis. Hypocalcemia is a rare and reversible cause of DCM. Here, we report a 50-year-old female with DCM, induced by idiopathic hypoparathyroidism, that improved after treatment with calcium.
Cardiomyopathy, dilated; Hypocalcemia; Hypoparathyroidism
Primary signet ring cell carcinoma of the colorectum detected at an early stage is very rare; most cases are detected at an advanced stage. Therefore, its prognosis is poorer than that of ordinary colorectal cancer. A 56-year-old Korean man was seen at this hospital for management of signet ring cell carcinoma of the colon. Colonoscopic examination revealed a IIa-like, ill-defined and flatly elevated 9-mm residual tumor in the cecum. Endoscopic mucosal resection was preformed. Pathological examination of the resected specimen revealed signet ring cell carcinoma that had invaded the lamina propria without venous or perineural invasion. Abdominal computed tomography (CT) and positron CT showed no evidence of primary lesions or distant metastasis. An additional laparoscopic right-hemicolectomy was performed; no residual tumor or lymph node metastasis was found. We report a case of primary signet ring cell carcinoma of the colon detected at an early stage and provide a review of the literature.
Colon carcinoma; Signet ring cell carcinoma; Primary carcinoma; Early stage; Endoscopic mucosal resection
We describe a 64-year-old male patient with panhypopituitarism who experienced polymorphic ventricular tachycardia (VT) associated with long QT intervals. The panhypopituitarism developed as a sequelae of radiation therapy administered 20 years prior to his current presentation and was recently aggravated by urinary tract infection with sepsis. In this case, polymorphic VT was resistant to conventional therapy (including magnesium infusion), and QT prolongation and T wave inversion were normalized after the administration of steroid and thyroid hormones. Thyroid hormone is generally known to be associated with torsades de pointes (TdP), but steroid or other hormones may also provoke TdP. Hormonal disorders should be considered as a cause of polymorphic VT with long QT intervals. Some arrhythmias can be life-threatening, and they can be prevented with supplementation of the insufficient hormone.
Tachycardia, ventricular; Torsades de pointes; Hypopituitarism; Radiotherapy
AIM: To investigate the relationship between the function of vagus nerve and peptide YY3-36 and ghrelin levels after subtotal gastrectomy.
METHODS: We enrolled a total of 16 patients who underwent subtotal gastrectomy due to gastric cancer. All surgeries were performed by a single skilled surgeon. We measured peptide YY3-36, ghrelin, leptin, insulin, growth hormone levels, and body weight immediately before and one month after surgery.
RESULTS: Vagus nerve preservation group showed less body weight loss and less increase of peptide YY3-36 compared with vagotomy group (-5.56 ± 2.24 kg vs -7.85 ± 1.57 kg, P = 0.037 and 0.06 ± 0.08 ng/mL vs 0.19 ± 0.12 ng/mL, P = 0.021, respectively). Moreover, patients with body weight loss of less than 10% exhibited reduced elevation of peptide YY3-36 level, typically less than 20% [6 (66.7%) vs 0 (0.0%), P = 0.011, odd ratio = 3.333, 95% confidence interval (1.293, 8.591)].
CONCLUSION: Vagus nerve preservation contributes to the maintenance of body weight after gastrectomy, and this phenomenon may be related to the suppressed activity of peptide YY3-36.
Anal cushion; Anal incontinence; Liquids continence test; Wexner score; Hemorrhoidectomy
AIM: To investigate the efficacy of cap-fitted colonoscopy (CFC) with regard to cecal intubation time.
METHODS: Two hundred and ninety-five patients undergoing screening colonoscopy at Gospel Hospital, Kosin University College of Medicine were enrolled in this randomized controlled trial between January and December 2010. Colonoscopies were conducted by a single endoscopist. Patient characteristics including age, sex, body mass index, history of abdominal surgery, quality of preparation, and the presence of diverticulosis were recorded.
RESULTS: One hundred and fifty patients were allocated into a CFC group and 145 into a non-CFC (NCF) group. Cecal intubations were achieved in all patients. Cecal intubation time in the CFC group was significantly shorter than in the NCF group for specific conditions: age ≥ 60 years, prior abdominal surgery, and poor bowel preparation. The number of detected adenomas was higher in the CFC group than in the NCF group (P = 0.040).
CONCLUSION: CFC facilitated shortening of the cecal intubation time in difficult cases, and was more sensitive for detecting adenomas than was NCF.
Colonoscopy; Cap-fitted colonoscopy; Cecal intubation
A 32‐year‐old woman without a remarkable history presented at the emergency department with strangulation of the neck. CT scans of the neck revealed a displaced cricoid fracture. Six days after admission to hospital, hoarseness and dyspnoea disappeared. On the 10th day, the patient was discharged without complications. The traditional treatment guidelines for laryngeal trauma have recommended an early surgical intervention after immediate tracheotomy in cases of displaced fractures of the cricoid cartilage. The patient could be treated successfully through continuous monitoring of airway obstruction without surgical management.
Circadian clocks are the endogenous oscillators that harmonize a variety of physiological processes within the body. Although many urinary functions exhibit clear daily or circadian variation in diurnal humans and nocturnal rodents, the precise mechanisms of these variations are as yet unclear. In the present study, we demonstrate that Per2 promoter activity clearly oscillates in neonate and adult bladders cultured ex vivo from Per2::Luc knock-in mice. In subsequent experiments, we show that multiple local oscillators are operating in all the bladder tissues (detrusor, sphincter and urothelim) and the lumbar spinal cord (L4–5) but not in the pontine micturition center or the ventrolateral periaqueductal gray of the brain. Accordingly, the water intake and urine volume exhibited daily and circadian variations in young adult wild-type mice but not in Per1−/−Per2−/− mice, suggesting a functional clock-dependent nature of the micturition rhythm. Particularly in PDK mice, the water intake and urinary excretion displayed an arrhythmic pattern under constant darkness, and the amount of water consumed and excreted significantly increased compared with those of WT mice. These results suggest that local circadian clocks reside in three types of bladder tissue and the lumbar spinal cord and may have important roles in the circadian control of micturition function.
bladder; circadian clock; lumbar spinal cord; peripheral oscillator; voiding; water intake
Background and Aims. Conventional endoscopic submucosal resection (EMR) of carcinoid tumors often involves the resection margin, which necessitates further intervention. Endoscopic submucosal dissection (ESD) is widely accepted for removing carcinoid tumors. We aimed to evaluate the clinical usefulness of ESD with that of EMR for resection of type I gastric carcinoid tumors. Patients and Methods. The study enrolled 62 patients (37 males, 25 females; median age, 50 years; range, 40–68 years) who were treated with EMR or ESD at three hospitals; the study group had 87 type I gastric carcinoid tumors with an estimated size of ≤10 mm. The complete resection rate and the complications associated with these two procedures were analyzed. Results. The overall ESD complete resection rate was higher than that of the EMR rate (94.9% versus 83.3%, P value = 0.174). A statistically lower vertical margin involvement rate was achieved when ESD was performed compared to when EMR was performed (2.6% versus 16.7%, P value = 0.038). The complication rate was not significantly different between the two groups. Conclusions. ESD showed a higher complete resection rate, particularly for the vertical margin, with a similar complication rate. We mildly recommend ESD rather than EMR for removing type I gastric carcinoid tumors.
A retrospective study.
To elucidate the causes of late revision following bone cement augmentation for osteoporotic vertebral compression fractures (OVCFs).
Overview of Literature
Percutaneous vertebroplasty (PVP) or kyphoplasty (KP) is thought to be effective for the treatment of OVCFs. Many complications related to PVP or KP have been reported. However, there is a paucity of reports regarding the causes of late revision surgery after failed PVP or KP.
Twenty six patients who developed unremitted back pain and/or progressive neurological deficit after a symptom-free period since treatment with PVP or KP were enrolled. All patients underwent cement removal and anterior reconstruction. Among the 26 patients, 22 patients underwent anterior interbody fusion combined with posterior instrumentation; 4 patients underwent anterior reconstruction only. The causes of revision surgery were assessed. Clinical results were assessed using a visual analogue scale (VAS) and Oswestry Disability Index (ODI). The complications were analyzed.
The average time to revision surgery was 18.9±14.6 months (range, 3-78 months). The causes of late revision surgery included 6 late infections, 8 progressive kyphoses, 10 proximal fractures after instrumented lumbar fusions, and 2 late neurological involvement. During the mean follow-up period of 13.5±7.8 months, pre-revision mean VAS (8.5±0.9) and ODI (81.2±12.5) were improved to 4.2±1.4 and 54.8±17.6, respectively. Five patients (19%) had serious complications after revision surgery.
This study presents complications of PVP or KP in the treatment of OVCFs although PVP or KP can be an effective treatment strategy for OVCF when applied in highly selected patients.
Osteoporosis; Spinal fractures; Vertebroplasty; Surgical revision
Tamsulosin, an α1-adrenoceptor antagonist, and sildenafil, a phosphodiesterase (PDE) inhibitor, are reported to improve lower urinary tract symptoms including overactive bladder (OAB). This study is aimed at investing the effects of tamsulosin and sildenafil and comparing the degree of the suppressive effects on the afferent pathways of micturition between them using an animal model of OAB, the spontaneously hypertensive rat (SHR).
The cystometric parameters, the basal pressure and duration of bladder contraction, were significantly increased in the SHR group as compared with the Wistar-Kyoto (WKY) group. The intercontraction interval also significantly decreased in the SHR group. In the SHR-Tam 0.01 mg/kg group and the SHR-Sil 1 mg/kg group, however, the basal pressure and duration were significantly reduced and the intercontraction interval was significantly prolonged. Moreover, the degree of the expression of c-Fos and NGF was significantly higher in the SHR group as compared with the WKY group. But it was significantly reduced in the SHR-Tam 0.01 mg/kg group and the SHR-Sil 1 mg/kg group. Furthermore, tamsulosin had a higher degree of effect as compared with sildenafil.
In conclusion, α1-adrenergic receptor antagonists and PDE-5 inhibitors may have an effect in improving the voiding functions through an inhibition of the neuronal activity in the afferent pathways of micturition.
Overactive bladder syndrome; Tamsulosin; Sildenafil; Neuronal activity; Afferent pathways of micturition
Achalasia is classified into 3 types according to the Chicago classification. The aim of this study was to investigate characteristics and treatment outcomes of 3 achalasia subtypes in Korean patients.
Fifty-five patients diagnosed with achalasia based on conventional or high-resolution esophageal manometry were consecutively enrolled. Their clinical characteristics, manometric, endoscopic and esophagographic findings and treatment responses were analyzed among the 3 subtypes of achalasia.
Of 55 patients, 21 (38.2%) patients had type I, 28 (50.9%) patients had type II and 6 (10.9%) patients had type III. The median follow-up period was 22.4 (interquartile range, 3.6-67.4) months. Type III patients were older than type I and II patients (70.0 vs. 46.2 and 47.6 years, P = 0.023). The width of the esophagus in type I patients was wider with more frequent bird's beak appearance on esophagogram than the other 2 types (P = 0.010 and 0.006, respectively). Of the 50 patients who received the evaluation for treatment response at 3 months, 7 patients (36.8% vs. 26.9%) were treated with pneumatic dilatation and 4 patients (21.1% vs. 15.4%) with laparoscopic Heller's myotomy in type I and II groups, respectively. The treatment responses of pneumatic dilatation and Heller's myotomy in type I group were 71.4 and 50.0% and in type II were 85.7 and 75.0%, respectively, and all 5 patients in type III group showed good response to medical therapy.
Clinical characteristics of 3 achalasia subtypes in Korean patients are consistent with other studies. Treatment outcomes are variable among 3 subtypes.
Esophageal achalasia; Esophageal motility disorders; Manometry
The increasing trend of antibiotic resistance requires effective second-line Helicobacter pylori (H. pylori) treatment in high prevalence area of H. pylori. The aim of our study was to evaluate the reinfection rate of H. pylori after second-line treatment that would determine the long-term follow up effect of the rescue therapy.
A total of 648 patients who had failed previous H. pylori eradication on standard triple therapy were randomized into two regimens: 1, esomeprazole (20 mg b.i.d), tripotassium dicitrate bismuthate (300 mg q.i.d), metronidazole (500 mg t.i.d), and tetracycline (500 mg q.i.d) (EBMT) or 2, moxifloxacin (400 mg q.d.), esomeprazole (20 mg b.i.d), and amoxicillin (1000 mg b.i.d.) (MEA). At four weeks after completion of eradication therapy, H. pylori tests were performed with 13C urea breath test or invasive tests. In patients who maintained continuous H. pylori negativity for the first year after eradication therapy, H. pylori status was assessed every year. For the evaluation of risk factors of reinfection, gender, age, clinical diagnosis, histological atrophic gastritis or intestinal metaplasia were analyzed.
The recrudescence rate of the EBMT was 1.7% and of the MEA group 3.3% (p = 0.67). The annual reinfection rate of H. pylori of EBMT was found to be 4.45% and the MEA group 6.46%. Univariate analysis (Log-rank test) showed no association with any clinical risk factor for reinfection.
The long-term reinfection rate of H. pylori stayed low in both of bismuth-containing quadruple therapy and moxifloxacin-based triple therapy; thus reinfection cannot affect the choice of second-line treatment.
Clinical Trial Registration Number NCT01792700
Helicobacter pylori; Reinfection; Quadruple; Moxifloxacin; Second-line
Stress has a deteriorating effect on hippocampal function. It also contributes to symptom exacerbation in many disease states, including overactive bladder and interstitial cystitis/bladder pain syndrome. We investigated the effects of various types of stresses (restraint, noise, and cold) on short-term memory and apoptosis in relation with corticotropin-releasing factor (CRF) expression.
Rats in the restraint stress group were restrained in a transparent Plexiglas cylinder for 60 minutes twice daily. Rats in the noise stress group were exposed to the 120 dB supersonic machine sound for 60 minutes twice daily. Rats in the cold stress group were placed in a cold chamber at 4℃ for 60 minutes twice daily. Each stress was applied for 10 days. A step-down avoidance test for short-term memory, immunohistochemistry for caspase-3 expression, and western blot analysis for Bax and Bcl-2 expressions were conducted.
Latency time was decreased and CRF expression in the hippocampal dentate gyrus and hypothalamic paraventricular nucleus were increased in all of the stress groups. The number of caspase-3-positive cells in the hippocampal dentate gyrus was increased and the expressions of Bax and Bcl2 in the hippocampus were decreased in all of the stress groups.
All of the stress groups experienced short-term memory impairment induced by apoptosis in the hippocampus. The present results suggest the possibility that these stresses affecting the impairment of short-term memory may also induce functional lower urinary tract disorders.
Restrain stress; Noise stress; Cold stress; Short-term memory; Apoptosis
The described oxime-based library protocol provides detailed procedures for the linkage of aminooxy functionality with aldehyde building blocks that result in the generation of libraries of multidentate inhibitors. Synthesis of inhibitors for protein tyrosine phosphatases (PTPs) and antagonists directed against the human tumor susceptibility gene 101 (Tsg101) are shown as examples. Three steps are involved: a) the design and synthesis of aminooxy platforms; b) tethering with aldehydes to form oxime-based linkages with sufficient purity; and c) direct in vitro biological evaluation of oxime products without purification. Each coupling reaction is a) performed in capped microtubes at room temperature; b) diluted for inhibitory evaluation and c) screened with targets in microplates to provide IC50 or Kd values. The synthesis of the aminooxy platforms takes 3–5 days; tethering with the aldehydes takes 24 h; and inhibition assay of enzymes and protein-protein interactions (PPIs) takes 30 min and 2 h respectively.
Oxime; aminooxy platform; multidentate inhibitors; PTP; YopH; PPIs; Tsg101; click chemistry
Sleep disturbances and emotional dysfunction are commonly associated with gastroeophageal reflux disease (GERD). The aims of this study were to evaluate GERD symptoms and disturbance in erosive reflux disease (ERD) and nonerosive reflux disease (NERD) patients, and to compare sleep dysfunction, depressive mood, anxiety and quality of life (QOL) among the control, ERD and NERD patients in Korea.
The Korean subjects were enrolled between 2010 and 2012, classified into 3 groups; the control group with no symptom and normal endoscopic findings, the ERD group with erosive esophagitis and the NERD group with more than one episode of heartburn or acid regurgitation per week, positive response to proton pump inhibitor, and normal endoscopic findings. Questionnaire included GERD symptoms, GERD impact scale (GIS) and daytime pathological sleepiness (Epworth sleepiness scale), sleep dysfunction (Pittsburgh sleep quality index, PSQI), depression and anxiety (Hospital anxiety and depression scale, HADS) and QOL (WHO quality of life scale abbreviated version, WHOQOL-BREF).
A total of 217 subjects were enrolled as follows; control (n = 70), ERD (n = 70) and NERD (n = 77). Impact of symptom of GIS score was higher in the NERD (9.2 ± 0.4) than in the ERD (6.5 ± 0.3) group (P < 0.001). Sleep dysfunctions were more frequent in GERD than the control group (PSQI score [P = 0.021]). Anxiety subscale of HAD score was higher in NERD (7.0 ± 0.5, P = 0.002) and ERD (6.2 ± 0.7, P = 0.004) groups than control (4.3 ± 0.7) group. WHOQOL-BREF scores in NERD (54.9 ± 2.3) and ERD (57.8 ± 2.4) groups were significantly lower than those in the control group (63.8 ± 2.4) (P = 0.002; P = 0.014, respectively).
The patients with NERD than ERD suffered more from the symptoms and disturbance in Korea. Sleep dysfunction and anxiety mood were higher and QOL was decreased in GERD, especially in NERD, suggesting that those factors might affect the severity of NERD.
Emotions; Gastroesophageal reflux; Quality of life; Sleep
Background and Purpose
Sudden cardiac death is one of the leading causes of death in patients with myotonic dystrophy type 1 (DM1). It has been proposed that a prolonged QT interval is associated with sudden cardiac death in several neurological diseases, including multiple system atrophy, idiopathic Parkinson's disease, and diabetic autonomic neuropathy. However, analyses of the corrected QT (QTc) interval in DM1 patients are rare in the literature. The purposes of this study were to determine the association between the QT interval and DM1, and the affecting factors.
Thirty-nine patients diagnosed with DM1 through genetic testing were enrolled. The QTc interval (calculated using Bazett's formula: QTc=QT/√RR) was compared between these patients and 39 normal healthy controls. The clinical and laboratory factors affecting QTc interval in the patient group were investigated.
The QTc interval was significantly longer in the DM1 group (411.2±44.7 msec, mean±SD) than in the normal control group (355.6±20.6 msec). Intragroup analysis revealed that a prolonged QTc interval in DM1 patients was associated with being female and older, having a longer disease duration, and exhibiting abnormal electrocardiography findings.
The higher incidence of sudden cardiac death in the DM1 population is associated with the observed prolonged QTc interval in those patients.
myotonic dystrophy; corrected QT interval; Bazett's formula; sudden cardiac death
Although the Ylang-Ylang aroma (YYA) has used as a general method for enhancing sedative effect, there was a little report on the efficacy of YYA on heart function using the electrocardiogram (EKG). Therefore, identifying of the effects of YYA on blood pressure (BP) and heart rate (HR) is important in order to demonstrate the effectiveness of YYA. The aim of this study was to investigate the effects of YYA on BP and HR in healthy men. Twenty-nine men took part in this study. The subjects were randomly divided into 2 groups: Ylang-Ylang group (YYG, n= 15) and control group (CG, n= 14). Physiological parameters recorded were BP by using a sphygmomanometer and HR by using an EKG. The present results demonstrated that inhalation of YYA significantly decreased the systolic and diastolic blood pressure. Inhalation of YYA also significantly decreased the HRs in 10 leads, except in lead I and aVR. This indicates that the HRs recorded in lead I and aVR were less sensitive or obtuse compared to those in the 10 other leads. Therefore, such a result reveals that it is necessary to be aware of the terms regarding the position. In the present results, YYA caused a reduction of HR and BP, and a relief of the arousal level in healthy men. The present results show a sedative effect of YYA, and this study provides some evidences for the usage of YYA in medicinal agent.
Ylang-Ylang; Heart rate; Systolic blood pressure; Diastolic blood pressure; Electrocardiogram
There has been no report regarding the regression of Barrett's esophagus (BE) by continuous treatment of proton pump inhibitor (PPI). The aim of this study was to determine the regression rate of BE by PPI and predictable markers related to regression.
Thirty-five patients diagnosed as BE were consecutively enrolled and most of them took continuous PPI. The 25 patients underwent endoscopic surveillance and received biopsy. If the specialized intestinal metaplasia (SIM) was lost at any point of surveillance and did not recur, the case was regarded as the regression group. The proportion of SIM was graded and the mucin phenotype was decided using immunohistochemistry for MUC2, MUC5AC and MUC6. To assess the cell proliferation indexes and the degree of intestinal maturation, immunohistochemistry for Ki67 and CDX2 were performed.
The regression of BE occurred in the 11 (44%) patients. The clinical and demographic factors showed no difference between the regression (n = 11) and persistence group (n = 14). The lower grade of SIM (P < 0.001) and gastric predominant mucin phenotype (P = 0.018) were more frequent, and the number of Ki67 positive cell per gland (P = 0.008) and the mean extent of CDX2 (P = 0.022) were lower in the regression group than in the persistence group.
The regression of BE by PPI treatment was frequent in Korea. The immunohistochemical detection of mucin phenotype, grade of SIM, Ki67 and CDX2 expression in Barrett's mucosa could be useful as a predictable marker for regression of SIM in BE.
Barrett esophagus; Biologic markers; Regression
This study evaluated the effect of Helicobacter pylori eradication on functional dyspepsia (FD), and the relationship between the changes of histological gastritis and FD symptom responses.
A total of 213 FD patients diagnosed by Rome III criteria were consecutively enrolled. H. pylori tests and gastritis grade by the Sydney system were performed before and 1 year after the proton pump based-eradication therapy for 7 days. Serum levels of pepsinogen, and genetic polymorphisms IL-6, IL-8 and IL-10 were investigated.
Total of 91 patients completed the 1 year follow-up. When the response rate of dyspepsia was compared at 1 year between the non-eradicated group (n = 24) and eradicated group (n = 67), each group showed complete response of 62.5% and 62.7%; satisfactory response (≥ 50%) of 0.0% and 19.4%; partial response (< 50%) of 12.5% and 11.9%; and refractory response of 25.0% and 6.0%, respectively (P = 0.015). In addition, the responder group (complete + satisfactory response) at 1 year showed improvement of activity and chronic inflammation in both the antrum and corpus (all P < 0.001). Multivariate analysis showed that H. pylori eradication (OR, 5.81; 95% CI, 1.07-31.59) and symptom improvement at 3 month (OR, 28.90; 95% CI, 5.29-157.82) were associated with the improvement of dyspepsia at 1 year. Among the successfully eradicated FD patients (n = 67), male (P = 0.013) and higher initial BMI (P = 0.016) were associated with the improvement of dyspepsia at 1 year.
H. pylori eradication improved FD symptoms, as well as gastritis at 1 year, suggesting that inflammation mediates FD.
Eradication; Functional dyspepsia; Helicobacter pylori
Thermosensation is mediated by ion channels that are highly temperature-sensitive. Several members of the family of transient receptor potential (TRP) ion channels are activated by cold or hot temperatures and have been shown to function as temperature sensors in vivo. The molecular mechanism of temperature-sensitivity of these ion channels is not understood. A number of domains or even single amino acids that regulate temperature-sensitivity have been identified in several TRP channels. However, it is unclear what precise conformational changes occur upon temperature activation. Here, we used the cysteine accessibility method to probe temperature-dependent conformations of single amino acids in TRP channels. We screened over 50 amino acids in the predicted outer pore domains of the heat-activated ion channels TRPV1 and TRPV3. In both ion channels we found residues that have temperature-dependent accessibilities to the extracellular solvent. The identified residues are located within the second predicted extracellular pore loop. These residues are identical or proximal to residues that were shown to be specifically required for temperature-activation, but not chemical activation. Our data precisely locate conformational changes upon temperature-activation within the outer pore domain. Collectively, this suggests that these specific residues and the second predicted pore loop in general are crucial for the temperature-activation mechanism of these heat-activated thermoTRPs.
Microneedles provide a minimally invasive means to transport molecules into the skin. A number of specific strategies have been employed to use microneedles for transdermal delivery.
The purpose of this study was to investigate the safety of two new digital microneedle devices (Digital Hand® and Digital Pro®; Bomtech Electronics Co., Ltd., Seoul, Korea) for the perforation of skin in skin-hairless-1 mice. This device replaces conventional needles and is designed specifically for intradermal delivery.
We used two newly developed digital microneedle devices to perforate the skin of skin-hairless-1 mice. We conducted a comparative study of the two digital microneedle devices and DTS® (Disk type-microneedle Therapy System; DTS lab., Seoul, Korea). To evaluate skin stability, we performed visual and dermatoscopic inspections, measurements of transepidermal water loss, and biopsies.
The two novel digital microneedle devices did not induce significant abnormalities of the skin on visual or dermatoscopic inspection, regardless of needle size (0.25~2.0 mm). No significant histopathological changes, such as inflammatory cell infiltration, desquamation of the stratum corneum, or disruption of the basal layer, were observed. The digital microneedle devices and microneedle therapy system produced similar results on measures of skin stability.
These two novel digital microneedle devices are safe transdermal drug delivery systems.
Digital; Mesotherapy; Safety; Water loss
Spontaneous reporting systems have several weak points, such as low reporting rates and insufficient clinical information. Active surveillance programs, such as ward rounds and a clinical data repository (CDR), may supplement the weak points of such systems. We developed active surveillance programs and compared them with existing spontaneous reporting.
We collected adverse drug event (ADE) cases, which comprised 1,055 cases of spontaneous reporting, 309 reported by ward rounds, and 229 found using a CDR. The clinical features and causative drugs were evaluated.
Active surveillance programs detected additional serious ADEs compared to those of spontaneous reporting programs. The ADEs identified by CDR (22.9%) were more likely to be classified as "serious" than those reported spontaneously (5.2%) or identified during ward rounds (10.3%). Causative drugs also differed. Opioids, antibiotics, and contrast media were the most common drugs causing ADEs in the spontaneous reporting system, whereas the active surveillance programs identified antibiotics as the most common causative drug. Clinical features also differed. ADEs with gastrointestinal manifestations were reported most frequently by spontaneous reporting programs. ADEs reported from active surveillance more reliably identified events associated with changes in laboratory values, such as hepatobiliary toxicity, hematologic manifestations, and nephrologic manifestations, compared with spontaneous reporting programs.
Our findings suggest that active surveillance programs can supplement spontaneous reporting systems in hospitals. ADEs related to laboratory abnormalities were monitored more closely by active surveillance programs and may be useful for identification of serious ADEs.
Drug toxicity; Spontaneous reporting; Active surveillance