Inhibition of angiotensin converting enzyme increases PKCβI isoform expression via activation of substance P and bradykinin receptors in cultured astrocytes of mice

Background@#Angiotensin-converting enzyme inhibitor (ACEi) inhibits the catalysis of angiotensin I to angiotensin II and the degradation of substance P (SP) and bradykinin (BK). While the possible relationship between ACEi and SP in nociceptive mice was recently suggested, the effect of ACEi on signal transduction in astrocytes remains unclear. @*Objectives@#This study examined whether ACE inhibition with captopril or enalapril modulates the levels of SP and BK in primary cultured astrocytes and whether this change modulates PKC isoforms (PKCα, PKCβI, and PKCε) expression in cultured astrocytes. @*Methods@#Immunocytochemistry and Western blot analysis were performed to examine the changes in the levels of SP and BK and the expression of the PKC isoforms in primary cultured astrocytes, respectively. @*Results@#The treatment of captopril or enalapril increased the immunoreactivity of SP and BK significantly in glial fibrillary acidic protein-positive cultured astrocytes. These increases were suppressed by a pretreatment with an angiotensin-converting enzyme.In addition, treatment with captopril increased the expression of the PKCβI isoform in cultured astrocytes, while there were no changes in the expression of the PKCα and PKCε isoforms after the captopril treatment. The captopril-induced increased expression of the PKCβI isoform was inhibited by a pretreatment with the neurokinin-1 receptor antagonist, L-733,060, the BK B 1 receptor antagonist, R 715, or the BK B 2 receptor antagonist, HOE 140. @*Conclusions@#These results suggest that ACE inhibition with captopril or enalapril increases the levels of SP and BK in cultured astrocytes and that the activation of SP and BK receptors mediates the captopril-induced increase in the expression of the PKCβI isoform.

Decrease of Muscle Mass in Young Patients With Neuromuscular Disease:Assessment of Sarcopenia

Background@#Sarcopenia can be associated with the disease etiologies other than degenerative processes, such as neurologic disease including cerebral palsy, myelomeningocele, or Duchenne muscular dystrophy, even in children. Although the relationship between neurologic disease and scoliosis or ambulatory function is known, the mediators affecting scoliosis or gait function in these patients are unclear, an example might be sarcopenia. This study aimed to assess the degree of sarcopenia in young patients with neurologic diseases using computed tomography (CT), and analyze the correlation between sarcopenia and scoliosis or ambulatory function. @*Methods@#Pediatric and young adult patients (≤ 25 years old) who underwent whole-spine or lower-extremity CT were retrospectively included. From bilateral psoas muscle areas (PMAs) at the L3 level, the psoas muscle z-score (PMz) and psoas muscle index [PMI = PMA/(L3 height) 2 ] were calculated. The t-test, Fisher’s exact test, and logistic regression analyses were performed. @*Results@#A total of 121 patients (56 men, mean age 12.2 ± 3.7 years) were included with 79 neurologic and 42 non-neurologic diseases. Patients with neurologic diseases had lower PMz (P = 0.013) and PMI (P = 0.026) than patients without. In neurologic disease patients, severe scoliosis patients showed lower PMz (P < 0.001) and PMI (P = 0.001). Non-ambulatory patients (n = 42) showed lower BMI (β = 0.727, P < 0.001) and PMz (β = 0.547, P = 0.025). In non-ambulatory patients, patients with severe scoliosis also showed lower PMz (P < 0.001) and PMI (P = 0.004). @*Conclusion@#Patients with neurologic diseases could have sarcopenia even in young age.Psoas muscle volume was also associated with ambulatory function in these patients.Sarcopenia was more severe in severe scoliosis patients in the non-ambulatory subgroup.

Latanoprostene Bunod 0.024% w/v Treatment of Open-anlge Glaucoma: Short-term Effects, Safety, and Changes in Ocular Blood

Purpose@#To study the short-term intraocular pressure (IOP)-lowering effect and optic nerve head (ONH) blood flow improvement after switching from latanoprost 0.005% w/v to latanoprostene bunod 0.024% w/v. @*Methods@#This prospective study ran from May 2022 to December 2022 and included 40 patients with open-angle glaucoma who switched from latanoprost 0.005% w/v to latanoprostene bunod 0.024% w/v. The IOP, ONH blood flow, and conjunctival hyperemia, corneal erosion, and eyelid pigmentation status were measured 3 months after switching. We recorded all possible side effects. @*Results@#The baseline IOP significantly dropped from 17.53 ± 6.49 to 16.00 ± 8.06 mmHg at 3 months (p = 0.032). The best-corrected visual acuity did not significantly change (0.24 ± 0.19 to 0.23 ± 0.16); neither did eyelid pigmentation (1.16 ± 0.78 to 1.16 ± 0.82) nor the corneal erosion score (0.58 ± 0.85 to 0.39 ± 0.76). Conjunctival hyperemia significantly decreased from 2.00 ± 0.69 to 1.67 ± 0.63 (p = 0.010). Neither the whole-image vessel density nor the peripapillary vessel density significantly changed. However, pruritus became significantly worse after the change (p = 0.008). @*Conclusions@#In the short term, latanoprostene bunod 0.024% w/v lowered the IOP more effectively than did latanoprost 0.005% w/v. However, there was no significant change in ONH blood flow after the switch.

Medical Representatives’ User Acceptance of Remote e-Detailing Technology: A Moderated Mediation Analysis of Technology Acceptance Model / 대한의료정보학회지

Objectives@#E-detailing methods have steadily evolved toward more contactless and interactive channels, which have received considerable attention during the coronavirus disease 2019 (COVID-19) crisis. Based on the technology acceptance model, this study attempted to identify medical representatives’ perceptions and attitudes towards individual innovativeness that affected users’ intentions to adopt new e-detailing devices utilizing information and communication technology. @*Methods@#The subjects of the current study were medical representatives at three major multinational or domestic pharmaceutical companies that operate in South Korea. In total, 300 questionnaires were distributed and 221 were returned. The survey elicited information on respondents’ perceived ease of use (PEOU), perceived usefulness (PU), personal innovativeness (PI), and user acceptance (UA) of remote e-detailing technology, in addition to demographic information and occupational characteristics. Structural equation models were fitted to the data. Separate analyses were conducted for different platform types, PCs and mobile devices. @*Results@#PEOU showed a statistically significant positive association with PU. PEOU, PU, and PI were associated with UA, and PI was a statistically significant moderator. On average, PEOU explained up to approximately 45% of the total variation in UA of remote e-detailing. @*Conclusions@#The analysis supports the framework of the technology acceptance model. PEOU was a substantially strong direct predictor of UA, and PI had a statistically significant, positive moderating effect between PU and UA. Medical representatives with pro-innovative attitudes are more likely to play the role of early adopters of remote e-detailing if they find this technology to be more useful.

Primary Tumor Suppression and Systemic Immune Activation of Macrophages through the Sting Pathway in Metastatic Skin Tumor

Purpose@#Agonists of the stimulator of interferon genes (STING) play a key role in activating the STING pathway by promoting the production of cytokines. In this study, we investigated the antitumor effects and activation of the systemic immune response of treatment with DMXAA (5,6-dimethylxanthenone-4-acetic acid), a STING agonist, in EML4-ALK lung cancer and CT26 colon cancer. @*Materials and Methods@#The abscopal effects of DMXAA in the treatment of metastatic skin nodules were assessed. EML4-ALK lung cancer and CT26 colon cancer models were used to evaluate these effects after DMXAA treatment. To evaluate the expression of macrophages and T cells, we sacrificed the tumor-bearing mice after DMXAA treatment and obtained the formalin-fixed paraffin-embedded (FFPE) tissue and tumor cells. Immunohistochemistry and flow cytometry were performed to analyze the expression of each FFPE and tumor cell. @*Results@#We observed that highly infiltrating immune cells downstream of the STING pathway had increased levels of chemokines after DMXAA treatment. In addition, the levels of CD80 and CD86 in antigen-presenting cells were significantly increased after STING activation. Furthermore, innate immune activation altered the systemic T cell-mediated immune responses, induced proliferation of macrophages, inhibited tumor growth, and increased numbers of cytotoxic memory T cells. Tumor-specific lymphocytes also increased in number after treatment with DMXAA. @*Conclusion@#The abscopal effect of DMXAA treatment on the skin strongly reduced the spread of EML4-ALK lung cancer and CT26 colon cancer through the STING pathway and induced the presentation of antigens.

Triolein emulsion enhances temozolomide brain delivery: an experimental study in rats.

PURPOSE: To evaluate the enhancement of temozolomide (TMZ) delivery in the rat brain using a triolein emulsion. MATERIALS AND METHODS: Rats were divided into the five groups as following: group 1 (negative control), group 2 (treated with triolein emulsion and TMZ 20 mg/kg), and group 3 (TMZ 20 mg/kg treatment without triolein), group 4 (treated with triolein emulsion and TMZ 10 mg/kg), and group 5 (TMZ 10 mg/kg treatment without triolein). Triolein emulsion was infused into the right common carotid artery. One hour later, the TMZ concentration was evaluated quantitatively and qualitatively using high-performance liquid chromatography (HPLC-MS) and desorption electrospray ionization mass spectrometry (DESI-MS) imaging, respectively. The concentration ratios of the ipsilateral to contralateral hemisphere in each group were determined and the statistical analysis was conducted using an unpaired t-test. RESULTS: Quantitatively, the TMZ concentration ratio of the ipsilateral to the control hemisphere was 2.41 and 1.13 in groups 2 and 3, and were 2.49 and 1.14 in groups 4 and 5, respectively. Thus, the TMZ signal intensities of TMZ in group 2 and 4 were statistically high in the ipsilateral hemispheres. Qualitatively, the signal intensity of TMZ was remarkably high in the ipsilateral hemisphere in group 2 and 4. CONCLUSIONS: The triolein emulsion efficiently opened the blood-brain barrier and could provide a potential new strategy to enhance the therapeutic effect of TMZ. HPLC-MS and DESI-MS imaging were shown to be suitable for analyses of enhancement of brain TMZ concentrations.

Clinical Features of Genetic Creutzfeldt-Jakob Disease with E200K Mutation

Although genetic Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disorder, cases of genetic CJD with E200K mutation are being increasingly reported in Korea. However, the clinical features and course of genetic CJD with E200K mutation in Korea remain unclear. We describe the clinical features and course of genetic CJD with E200K mutation in a patient who initially presented with rapid progressive memory impairment and myoclonus.

Clinical Features of Genetic Creutzfeldt-Jakob Disease with E200K Mutation

Although genetic Creutzfeldt-Jakob disease (CJD) is a rare neurodegenerative disorder, cases of genetic CJD with E200K mutation are being increasingly reported in Korea. However, the clinical features and course of genetic CJD with E200K mutation in Korea remain unclear. We describe the clinical features and course of genetic CJD with E200K mutation in a patient who initially presented with rapid progressive memory impairment and myoclonus.

Bee venom reduces burn-induced pain via the suppression of peripheral and central substance P expression in mice

Background@#Scalding burn injuries can occur in everyday life but occur more frequently in young children. Therefore, it is important to develop more effective burn treatments. @*Objectives@#This study examined the effects of bee venom (BV) stimulation on scalding burn injury-induced nociception in mice as a new treatment for burn pain. @*Methods@#To develop a burn injury model, the right hind paw was immersed temporarily in hot water (65°C, 3 seconds). Immediately after the burn, BV (0.01, 0.02, or 0.1 mg/kg) was injected subcutaneously into the ipsilateral knee area once daily for 14 days. A von Frey test was performed to assess the nociceptive response, and the altered walking parameters were evaluated using an automated gait analysis system. In addition, the peripheral and central expression changes in substance P (Sub P) were measured in the dorsal root ganglion and spinal cord by immunofluorescence. @*Results@#Repeated BV treatment at the 2 higher doses used in this study (0.02 and 0.1 mg/kg) alleviated the pain responses remarkably and recovered the gait performances to the level of acetaminophen (200 mg/kg, intraperitoneal, once daily), which used as the positive control group. Moreover, BV stimulation had an inhibitory effect on the increased expression of Sub P in the peripheral and central nervous systems by a burn injury. @*Conclusions@#These results suggest that a peripheral BV treatment may have positive potency in treating burn-induced pain.

Narcolepsy, How do We Manage it?

Narcolepsy is a chronic neurologic disorder characterized by excessive daytime sleepiness and cataplexy arising from dysregulation of pathway controlling the wake and sleep states. Despite advances in our understanding of the pathophysiology of narcolepsy, to date, only symptomatic treatments exist for this disease. Especially in Korea, only limited medication for narcolepsy has been available. In general, psychostimulants such as modafinil, armodafinil, and methylphenidate were prescribed to improve wakefulness, and cataplexy was managed with antidepressants. Recently many new agents has been developed and widely used in the United States and European countries. Some of those medications are expected to be available in Korea soon. Education of lifestyle modification and regular naps are also important strategy for the treatment of narcolepsy. This review summarizes briefly current and future medication, and nonpharmacological management of narcolepsy as well.

Radiography and ct features of atherosclerosis in two miniature schnauzer dogs

Two miniature Schnauzer dogs with chronic pancreatitis were investigated. Both dogs showed systemic hypertension and increased concentrations of triglycerides and C-reactive protein. Abdominal radiography revealed cylindrical calcification in the retroperitoneum, and computed tomography (CT) showed extensive calcification of the abdominal and peripheral arteries in both dogs. Metastases and other dystrophic conditions that can cause arterial calcification were excluded based on the laboratory tests, and the dogs were diagnosed with atherosclerosis ante mortem. Atherosclerosis should be considered when extensive arterial calcification is observed on abdominal radiography or CT in miniature Schnauzers.

Phylogenetic Positioning of a Strongyloides stercoralis Isolate Recovered from a Korean Patient and Comparison with Other Asian Isolates

Strongyloidiasis is caused by Strongyloides stercoralis and is one of the most neglected tropical diseases in tropical and subtropical regions. Although several strongyloidiasis cases have been reported in Korea, genetic analysis of Korean isolates is still incomplete. In this study, a parasite was isolated from a 61-year-old man diagnosed with strongyloidiasis during the treatment of lymphoma on his retroperitoneal lymph node. Diffuse symmetric wall thickening from the ascending to descending colon and a nematode-infected intestine was observed following microscopic examination. Genomic DNA was isolated from a patient tissue block, and S. stercoralis was identified by PCR and sequencing (18S rDNA). In order to determine phylogenetic location of a Korean isolate (named KS1), we analyzed cox1 gene (500-bp) and compared it with that from 47 previous S. stercoralis isolates (28 human isolates and 19 canid isolates) from Asian countries. Our results showed that phylogenetic tree could clearly be divided into 5 different groups according to hosts and regions. KS1 was most closely related with the Chinese isolates in terms of genetic distance.

Percutaneous Trans-splenic Obliteration for Duodenal Variceal bleeding: A Case Report / 대한소화기학회지

Duodenal varices are a serious complication of portal hypertension. Bleeding from duodenal varices is rare, but when bleeding does occur, it is massive and can be fatal. Unfortunately, the optimal therapeutic modality for duodenal variceal bleeding is unclear. This paper presents a patient with duodenal variceal bleeding that was managed successfully using percutaneous trans-splenic variceal obliteration (PTVO). A 56-year-old man with a history of alcoholic cirrhosis presented with a 6-day history of melena. Emergency esophagogastroduodenoscopy revealed a large, bluish mass with a nipple sign in the second portion of the duodenum. Coil embolization of the duodenal varix was performed via a trans-splenic approach (i.e., PTVO). The patient no longer complained of melena after treatment. The duodenal varix was no longer visible at the follow-up esophagogastroduodenoscopy performed three months after PTVO. The use of PTVO might be a viable option for the treatment of duodenal variceal bleeding.

Diagnostic Accuracy of Different Machine Learning Algorithms for Obstructive Sleep Apnea

Objectives@#The objective of this study was to develop models for predicting obstructive sleep apnea (OSA) based on easily obtainable clinical information of patients using various machine learning techniques. @*Methods@#We used a data set that included the records of 1,368 patients, in which 1,074 patients were male (78.5 %), and 294 patients were female (21.5 %). We randomly divided the data into a training set (1,000) and test set (368). Five machine learning methods, i.e., support vector machine model, lasso logit model, naïve bayes, discriminant analysis, and K-nearest neighbor (KNN), with a 10-cross fold technique were used with the proposed model to predict OSA. We evaluated the accuracy, sensitivity, specificity, and precision of each model for three thresholds [Apnea-Hypopnea Index (AHI)≥5, AHI≥15, and AHI≥30]. @*Results@#Among the machine learning techniques, KNN showed the best results compared to the other techniques. The accuracy, sensitivity, specificity, and precision of OSA prediction were 87.0%, 91.0%, 74.4%, and 91.9%, respectively, based on AHI≥5. When the threshold of OSA was AHI≥15 or AHI≥30, KNN provided lower accuracy (79.6% each) and precision (79.0% and 68.7%), which were still higher than those of the other techniques. @*Conclusions@#The model derived from the KNN technique exhibited the best performance based on its highest level of accuracy. We demonstrate that this model is a useful tool for predicting OSA.

Phylogenetic Positioning of a Strongyloides stercoralis Isolate Recovered from a Korean Patient and Comparison with Other Asian Isolates

Strongyloidiasis is caused by Strongyloides stercoralis and is one of the most neglected tropical diseases in tropical and subtropical regions. Although several strongyloidiasis cases have been reported in Korea, genetic analysis of Korean isolates is still incomplete. In this study, a parasite was isolated from a 61-year-old man diagnosed with strongyloidiasis during the treatment of lymphoma on his retroperitoneal lymph node. Diffuse symmetric wall thickening from the ascending to descending colon and a nematode-infected intestine was observed following microscopic examination. Genomic DNA was isolated from a patient tissue block, and S. stercoralis was identified by PCR and sequencing (18S rDNA). In order to determine phylogenetic location of a Korean isolate (named KS1), we analyzed cox1 gene (500-bp) and compared it with that from 47 previous S. stercoralis isolates (28 human isolates and 19 canid isolates) from Asian countries. Our results showed that phylogenetic tree could clearly be divided into 5 different groups according to hosts and regions. KS1 was most closely related with the Chinese isolates in terms of genetic distance.

Percutaneous Trans-splenic Obliteration for Duodenal Variceal bleeding: A Case Report / 대한소화기학회지

Duodenal varices are a serious complication of portal hypertension. Bleeding from duodenal varices is rare, but when bleeding does occur, it is massive and can be fatal. Unfortunately, the optimal therapeutic modality for duodenal variceal bleeding is unclear. This paper presents a patient with duodenal variceal bleeding that was managed successfully using percutaneous trans-splenic variceal obliteration (PTVO). A 56-year-old man with a history of alcoholic cirrhosis presented with a 6-day history of melena. Emergency esophagogastroduodenoscopy revealed a large, bluish mass with a nipple sign in the second portion of the duodenum. Coil embolization of the duodenal varix was performed via a trans-splenic approach (i.e., PTVO). The patient no longer complained of melena after treatment. The duodenal varix was no longer visible at the follow-up esophagogastroduodenoscopy performed three months after PTVO. The use of PTVO might be a viable option for the treatment of duodenal variceal bleeding.

Diagnostic Accuracy of Different Machine Learning Algorithms for Obstructive Sleep Apnea

Objectives@#The objective of this study was to develop models for predicting obstructive sleep apnea (OSA) based on easily obtainable clinical information of patients using various machine learning techniques. @*Methods@#We used a data set that included the records of 1,368 patients, in which 1,074 patients were male (78.5 %), and 294 patients were female (21.5 %). We randomly divided the data into a training set (1,000) and test set (368). Five machine learning methods, i.e., support vector machine model, lasso logit model, naïve bayes, discriminant analysis, and K-nearest neighbor (KNN), with a 10-cross fold technique were used with the proposed model to predict OSA. We evaluated the accuracy, sensitivity, specificity, and precision of each model for three thresholds [Apnea-Hypopnea Index (AHI)≥5, AHI≥15, and AHI≥30]. @*Results@#Among the machine learning techniques, KNN showed the best results compared to the other techniques. The accuracy, sensitivity, specificity, and precision of OSA prediction were 87.0%, 91.0%, 74.4%, and 91.9%, respectively, based on AHI≥5. When the threshold of OSA was AHI≥15 or AHI≥30, KNN provided lower accuracy (79.6% each) and precision (79.0% and 68.7%), which were still higher than those of the other techniques. @*Conclusions@#The model derived from the KNN technique exhibited the best performance based on its highest level of accuracy. We demonstrate that this model is a useful tool for predicting OSA.

Surgical Treatment for a Broken Acupuncture Needle in the Retroperitoneal Space: A Case Report / 대한신경손상학회지

Acupuncture is a well-known traditional medical procedure in Korea and is being increasingly used to treat various conditions including pain control, especially among the older generation. However, several problems related to acupuncture have been reported. A 27-year-old woman expressed that she had back pain occurring despite her posture. She received acupuncture therapy 2 months prior. We discovered a needle-shaped foreign material near the T12 vertebra body in the retroperitoneum. We extracted 2 pieces of deteriorated broken needles by laparoscopy. Postoperatively, the woman was discharged within 5 days with no complications.We report a patient that received laparoscopy with a full recovery after having severe back pain caused by a broken needle which was stuck in the retroperitoneum.

Treatment Experiences of Traumatic Brain Injury Patients using DoctorHelicopter Emergency Medical Service: Early Data in a Regional Trauma Center / 대한신경손상학회지

Objective@#The purpose of this study is to analyze the results of doctor helicopter emergency medical service (HEMS) in traumatic brain injury (TBI) patients and to understand the effect and improvement of doctor HEMS. @*Methods@#We included TBI patients transferred by doctor HEMS of our hospital between February 2016 and December 2017. Basic characteristics, HEMS data, treatment and results data were analyzed retrospectively. We divided the patients into 3 groups as regarding severity of patient, relevance of treatment and transfer. We investigated the preventable trauma death rate (PTDR) of these groups to increase the reliability of the treatment outcome. @*Results@#TBI patients using doctor HEMS were indicated in 98 patients (18.7%) among 522 overall HEMS patients. The overall mortality was consisted in 21.4% and 43.2% was resulted in Glasgow outcome scale 4 or 5. The group of proper transport and treatment for severe TBI was consisted in 62.2% including 13 mortality cases and no preventable death. The group of delayed transport or treatment for severe TBI was 18.3% including 8 mortality cases and 1 preventable death. The PTDR of TBI after doctor HEMS was significantly lower than that of overall TBI (4.8% vs. 11.6%, p=0.045). @*Conclusion@#In patients with severe TBI, doctor HEMS can improve treatment outcomes by reducing treatment delay and unnecessary examinations and this result was evidenced that the PTDR were decreased significantly after doctor HEMS transport. The appropriate treatment is mandatory for real-time communication with the emergency doctor and treatment preparation of the trauma team during the HEMS transport.

Severe Hypophosphatemia-Induced Acute Toxic-Metabolic Encephalopathy in Continuous Renal Replacement Therapy

Acute toxic-metabolic encephalopathy (TME) is an acute condition of global cerebral dysfunction in the absence of primary structural brain disease. Severe hypophosphatemia leads to muscle weakness and involves the diaphragm but hypophosphatemia-induced TME is very rare. Herein, we report the case of a 43-year-old woman with encephalopathy with severe hypophosphatemia during continuous renal replacement therapy. She presented with features of oliguric acute kidney injury on diabetic kidney disease due to volume depletion. At admission, her mental status was alert but gradually changed to stupor mentation during continuous renal replacement therapy. Her phosphate level was less than 0.41 mEq/L and Glasgow coma scale decreased from 15 to 5. After phosphate intravenous replacement and administration of phosphate-containing replacement solution, the phosphate level increased to 2.97 mEq/L and mental state returned to alert state. This case demonstrates that the level of phosphorus should be observed during continuous renal replacement therapy.