What is needed to increase the professional competencies of the military emergency medical technicians of the Republic of Korea Air Force? / 보건의료교육평가

No abstract available.

Changes in the Expressions of Iba1 and Calcitonin Gene-Related Peptide in Adjacent Lumbar Spinal Segments after Lumbar Disc Herniation in a Rat Model

Lumbar disc herniation is commonly encountered in clinical practice and can induce sciatica due to mechanical and/or chemical irritation and the release of proinflammatory cytokines. However, symptoms are not confined to the affected spinal cord segment. The purpose of this study was to determine whether multisegmental molecular changes exist between adjacent lumbar spinal segments using a rat model of lumbar disc herniation. Twenty-nine male Sprague-Dawley rats were randomly assigned to either a sham-operated group (n=10) or a nucleus pulposus (NP)-exposed group (n=19). Rats in the NP-exposed group were further subdivided into a significant pain subgroup (n=12) and a no significant pain subgroup (n=7) using mechanical pain thresholds determined von Frey filaments. Immunohistochemical stainings of microglia (ionized calcium-binding adapter molecule 1; Iba1), astrocytes (glial fibrillary acidic protein; GFAP), calcitonin gene-related peptide (CGRP), and transient receptor potential vanilloid 1 (TRPV1) was performed in spinal dorsal horns and dorsal root ganglions (DRGs) at 10 days after surgery. It was found immunoreactivity for Iba1-positive microglia was higher in the L5 (P=0.004) dorsal horn and in the ipsilateral L4 (P=0.009), L6 (P=0.002), and S1 (P=0.002) dorsal horns in the NP-exposed group than in the sham-operated group. The expression of CGRP was also significantly higher in ipsilateral L3, L4, L6, and S1 segments and in L5 DRGs at 10 days after surgery in the NP-exposed group than in the sham-operated group (P<0.001). Our results indicate that lumbar disc herniation upregulates microglial activity and CGRP expression in many adjacent and ipsilateral lumbar spinal segments.

Effects of DA-9701, a Novel Prokinetic Agent, on Phosphorylated Extracellular Signal-Regulated Kinase Expression in the Dorsal Root Ganglion and Spinal Cord Induced by Colorectal Distension in Rats

BACKGROUND/AIMS: DA-9701, a standardized extract of Pharbitis Semen and Corydalis Tuber, is a new prokinetic agent that exhibits an analgesic effect on the abdomen. We investigated whether DA-9701 affects visceral pain induced by colorectal distension (CRD) in rats. METHODS: A total of 21 rats were divided into three groups: group A (no CRD+no drug), group B (CRD+no drug), and group C (CRD+DA-9701). Expression of pain-related factors, substance P (SP), c-fos, and phosphorylated extracellular signal-regulated kinase (p-ERK) in the dorsal root ganglion (DRG) and spinal cord was determined by immunohistochemical staining and Western blotting. RESULTS: The proportions of neurons in the DRG and spinal cord expressing SP, c-fos, and p-ERK were higher in group B than in group A. In the group C, the proportion of neurons in the DRG and spinal cord expressing p-ERK was lower than that in group B. Western blot results for p-ERK in the spinal cord indicated a higher level of expression in group B than in group A and a lower level of expression in group C than in group B. CONCLUSIONS: DA-9701 may decrease visceral pain via the downregulation of p-ERK in the DRG and spinal cord.

Attenuation of Spinal Cord Injury-Induced Astroglial and Microglial Activation by Repetitive Transcranial Magnetic Stimulation in Rats

Spinal cord injury (SCI) causes not only loss of sensory and motor function below the level of injury but also chronic pain, which is difficult and challenging of the treatment. Repetitive transcranial magnetic stimulation (rTMS) to the motor cortex, of non-invasive therapeutic methods, has the motor and sensory consequences and modulates pain in SCI-patients. In the present study, we studied the effectiveness of rTMS and the relationship between the modulation of pain and the changes of neuroglial expression in the spinal cord using a rat SCI-induced pain model. Elevated expressions of Iba1 and GFAP, specific microglial and astrocyte markers, was respectively observed in dorsal and ventral horns at the L4 and L5 levels in SCI rats. But in SCI rats treated with 25 Hz rTMS for 8 weeks, these expressions were significantly reduced by about 30%. Our finding suggests that this attenuation of activation by rTMS is related to pain modulation after SCI. Therefore, rTMS might provide an alternative means of attenuating neuropathic pain below the level of SCI.

A case of polymyositis associated with Hashimoto's thyroiditis

No abstract available.

An Autopsy Case of Amyotrophic Lateral Sclerosis with Neuroinflammatory change

Neuroinflammation such as reactive gliosis and microglial activations are important pathological findings of ALS. We present a first autopsy case of ALS in Korea related with neuroinflammatory change. A 67-year-old ALS patient suddenly expired due to accidental head trauma. Gross autopsy finding showed marked atrophic change in spinal cord. Pathological finding include a marked loss of motor neurons, reactive gliosis and microglial infiltrations. These findings suggest neuroinflammation may play a role in pathogenesis of ALS.

The Effect of Minocycline on Motor Neuron Recovery and Neuropathic Pain in a Rat Model of Spinal Cord Injury

OBJECTIVE: Minocycline, a second-generation tetracycline-class antibiotic, has been well established to exert a neuroprotective effect in animal models and neurodegenerative disease through the inhibition of microglia. Here, we investigated the effects of minocycline on motor recovery and neuropathic pain in a rat model of spinal cord injury. METHODS: To simulate spinal cord injury, the rats' spinal cords were hemisected at the 10th thoracic level (T10). Minocycline was injected intraperitoneally, and was administered 30 minutes prior surgery and every second postoperative day until sacrifice 28 days after surgery. Motor recovery was assessed via the Basso-Beattie-Bresnahan test. Mechanical hyperalgesia was measured throughout the 28-day post-operative course via the von Frey test. Microglial and astrocyte activation was assessed by immunohistochemical staining for ionized calcium binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) at two sites: at the level of hemisection and at the 5th lumbar level (L5). RESULTS: In rats, spinal cord hemisection reduced locomotor function and induced a mechanical hyperalgesia of the ipsilateral hind limb. The expression of Iba1 and GFAP was also increased in the dorsal and ventral horns of the spinal cord at the site of hemisection and at the L5 level. Intraperitoneal injection of minocycline facilitated overall motor recovery and attenuated mechanical hyperalgesia. The expression of Iba1 and GFAP in the spinal cord was also reduced in rats treated with minocycline. CONCLUSION: By inhibiting microglia and astrocyte activation, minocycline may facilitate motor recovery and attenuate mechanical hyperalgesia in individuals with spinal cord injuries.

Prior Use of 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A Reductase Inhibitor, Simvastatin Fails to Improve Outcome after Experimental Intracerebral Hemorrhage

OBJECTIVE: Contrary to some clinical belief, there were quite a few studies regarding animal models of intracerebral hemorrhage (ICH) in vivo suggesting that prior use of statins may improve outcome after ICH. This study reports the effect of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitor, simvastatin given before experimental ICH. METHODS: Fifty-one rats were subjected to collagenase-induced ICH, subdivided in 3 groups according to simvastatin treatment modality, and behavioral tests were done. Hematoma volume, brain water content and hemispheric atrophy were analyzed. Immunohistochemical staining for microglia (OX-42) and endothelial nitric oxide synthase (eNOS) was performed and caspase-3 activity was also measured. RESULTS: Pre-simvastatin therapy decreased inflammatory reaction and perihematomal cell death, but resulted in no significant reduction of brain edema and no eNOS expression in the perihematomal region. Finally, prior use of simvastatin showed less significant improvement of neurological outcome after experimental ICH when compared to post-simvastatin therapy. CONCLUSION: The present study suggests that statins therapy after ICH improves neurological outcome, but prior use of statins before ICH might provide only histological improvement, providing no significant impact on neurological outcome against ICH.

Effects of Continuous Repetitive Transcranial Magnetic Stimulation on Pain Response in Spinal Cord Injured Rat

OBJECTIVE: To investigate the effects of continuous repetitive transcranial magnetic stimulation (rTMS) on pain response in spinal cord injured rat. METHOD: Forty Sprague-Dawley rats (200~250 grams, female) were used. Thoracic spinal cord (T9) was contused using New York University (NYU) spinal cord impactor. Ten gram weight rod was dropped from a height of 25 mm to produce spinal cord contusion model with moderate injury. The animals were randomly assigned to two groups: one exposed to real magnetic stimulation (real-rTMS group) and the other not exposed to magnetic stimulation (sham-rTMS group). rTMS was applied for 8 weeks. To assess the effect of continuous rTMS on below-level pain responses after spinal cord injury (SCI), the hindpaw withdrawal response for thermal stimuli, cold stimuli and mechanical stimuli were compared between two groups. RESULTS: Behavioral response for pain showed that hindpaw withdrawal response for cold stimuli was reduced significantly from 4 weeks after SCI in real-rTMS group compared with sham group (p<0.05). CONCLUSION: These results suggest that continuous rTMS may have beneficial effects on attenuation of cold allodynia after SCI, and it might be an additional non-invasive therapeutic method in patients with chronic neuropathic pain after SCI.

A Case of Gastric Non-Hodgkin's Lymphoma That Developed in a Patient with Behcet's Disease / 대한소화기내시경학회지

Behcet's disease is chronic, relapsing, multi-systemic inflammatory vasculitis. Unlikely the other autoimmune diseases, gastric non-Hodgkin's lymphoma has rarely been reported in a patient with Behcet's disease. We report here on a 40-year-old man who had Behcet's disease for several years and who suffered recurrent oral ulcer, genital ulcer and skin lesion. The patient was treated with azathioprine and intermittent oral steroid. He complained of epigastric pain for 1 month, and he had a large ulcerative lesion seen on endoscopic evaluation. We confirmed the lesion was a gastric, diffuse, large B cell lymphoma by endoscopic biopsy. The patient was treated with the rituximab-CHOP regimen, and he has achieved a complete remission for 3 years. We report here on a case of gastric non-Hodgkin's lymphoma in a patient with Behcet's disease and who also had an ileocecal valve ulcer.

A Case of Pseudomembranous Aspergillus Tracheobronchitis in a Patient with Diabetes Mellitus

Aspergillus tracheobronchitis is one form of invasive pulmonary aspergillosis which is characterized by ulcers and pseudomembrane formation in tracheobronchial tree. In Aspergillus tracheobronchitis, the infection is often limited to the mucosa and it accounts for less than 10 percents of invasive disease. Invasive aspergillosis mainly occurs in immunocompromized patients with prolonged neutropenia, advanced AIDS, organ transplantation, high-dose glucocorticoid therapy or cytotoxic therapy although it can occur in less immunocompromised patients, such as after influenza, COPD, old age, and diabetes. We report a case of Aspergillus tracheobronchitis in a 61 year-old patient with diabetes and Child Pugh class A liver cirrhosis. He presented with cough and purulent sputum for 10 days. He was diagnosed by bronchoscopy and successfully treated with antifungal therapy.

Bacteriologic Analysis of Expectorated Sputum in Patient with Bronchiectasis / 결핵및호흡기질환

BACKGROUND: Bronchiectasis (BE) remains a rare respiratory disease in Korea. This retrospective study was done to investigate the potential pathogenic microorganisms (PPMs) that cause in patients with BE, through the use of sputum specimens. METHODS: One hundred eleven adult patients, who had undergone chest computed tomography (CT), sputum gram stain/culture, and BE detected by chest CT, were included in this study. Sputum adequacy was determined by using Murray-Washington classification. RESULTS: The mean (+/-SD) age of patients was 60.9 (+/-14.0). The number of PPMs was 167 (67%) in the total 248 isolated organisms. The most frequent PPMs were P. aeruginosa (23.4%), K. pneumoniae (10.5%), and S. aureus (8.4%). The proportion of adequate sputum (AS) was 25.8% in the total sputum specimens. The patients with AS were 41 (37%) and the patients with inadequate sputum (IS) were 70 (63%). The proportion of P. aeruginosa was higher in AS compared to that of IS (44% vs. 19%, p=0.004). The BE score was also higher in P. aeruginosa (+) patients compared to that of P. aeruginosa (-) patients (10.8 vs. 7.6, p=0.001). CONCLUSION: Although the proportion of AS in the total sputum was low, PPMs were isolated in most patients with BE. It is likely that P. aeruginosa was isolated in AS and AS patients had higher BE scores.

Proinflammatory Cytokine and Nitric Oxide Production by Human Macrophages Stimulated with Trichomonas vaginalis

Trichomonas vaginalis commonly causes vaginitis and perhaps cervicitis in women and urethritis in men and women. Macrophages are important immune cells in response to T. vaginalis infection. In this study, we investigated whether human macrophages could be involved in inflammation induced by T. vaginalis. Human monocyte-derived macrophages (HMDM) were co-cultured with T. vaginalis. Live, opsonized-live trichomonads, and T. vaginalis lysates increased proinflammatory cytokines, such as TNF-alpha, IL-1beta, and IL-6 by HMDM. The involvement of nuclear factor (NF)-kappaB signaling pathway in cytokine production induced by T. vaginalis was confirmed by phosphorylation and nuclear translocation of p65 NF-kappaB. In addition, stimulation with live T. vaginalis induced marked augmentation of nitric oxide (NO) production and expression of inducible NO synthase (iNOS) levels in HMDM. However, trichomonad-induced NF-kappaB activation and TNF-alpha production in macrophages were significantly inhibited by inhibition of iNOS levels with L-NMMA (NO synthase inhibitor). Moreover, pretreatment with NF-kappaB inhibitors (PDTC or Bay11-7082) caused human macrophages to produce less TNF-alpha. These results suggest that T. vaginalis stimulates human macrophages to produce proinflammatory cytokines, such as IL-1, IL-6, and TNF-alpha, and NO. In particular, we showed that T. vaginalis induced TNF-alpha production in macrophages through NO-dependent activation of NF-kappaB, which might be closely involved in inflammation caused by T. vaginalis.

Proinflammatory Cytokine and Nitric Oxide Production by Human Macrophages Stimulated with Trichomonas vaginalis

Trichomonas vaginalis commonly causes vaginitis and perhaps cervicitis in women and urethritis in men and women. Macrophages are important immune cells in response to T. vaginalis infection. In this study, we investigated whether human macrophages could be involved in inflammation induced by T. vaginalis. Human monocyte-derived macrophages (HMDM) were co-cultured with T. vaginalis. Live, opsonized-live trichomonads, and T. vaginalis lysates increased proinflammatory cytokines, such as TNF-alpha, IL-1beta, and IL-6 by HMDM. The involvement of nuclear factor (NF)-kappaB signaling pathway in cytokine production induced by T. vaginalis was confirmed by phosphorylation and nuclear translocation of p65 NF-kappaB. In addition, stimulation with live T. vaginalis induced marked augmentation of nitric oxide (NO) production and expression of inducible NO synthase (iNOS) levels in HMDM. However, trichomonad-induced NF-kappaB activation and TNF-alpha production in macrophages were significantly inhibited by inhibition of iNOS levels with L-NMMA (NO synthase inhibitor). Moreover, pretreatment with NF-kappaB inhibitors (PDTC or Bay11-7082) caused human macrophages to produce less TNF-alpha. These results suggest that T. vaginalis stimulates human macrophages to produce proinflammatory cytokines, such as IL-1, IL-6, and TNF-alpha, and NO. In particular, we showed that T. vaginalis induced TNF-alpha production in macrophages through NO-dependent activation of NF-kappaB, which might be closely involved in inflammation caused by T. vaginalis.

Neurochemical Characterization of the TRPV1-Positive Nociceptive Primary Afferents Innervating Skeletal Muscles in the Rats

OBJECTIVE: Transient receptor potential vanilloid subfamily type 1 (TRPV1), a most specific marker of the nociceptive primary afferent, is expressed in peptidergic and non-pepetidergic primary afferents innervating skin and viscera. However, its expression in sensory fibers to skeletal muscle is not well known. In this study, we studied the neurochemical characteristics of TRPV1-positive primary afferents to skeletal muscles. METHODS: Sprague-Dawley rats were injected with total 20 microliter of 1% fast blue (FB) into the gastrocnemius and erector spinae muscle and animals were perfused 4 days after injection. FB-positive cells were traced in the L4-L5 (for gastrocnemius muscle) and L2-L4 (for erector spinae muscle) dorsal root ganglia. The neurochemical characteristics of the muscle afferents were studied with multiple immunofluorescence with TRPV1, calcitonin gene-related peptide (CGRP) and P2X(3). To identify spinal neurons responding to noxious stimulus to the skeletal muscle, 10% acetic acids were injected into the gastrocnemius and erector spinae muscles and expression of phospho extracellular signal-regulated kinase (pERK) in spinal cords were identified with immunohistochemical method. RESULTS: TRPV1 was expressed in about 49% of muscle afferents traced from gastrocnemius and 40% of erector spinae. Sixty-five to 60% of TRPV1-positive muscles afferents also expressed CGRP. In contrast, expression of P2X3 immnoreaction in TRPV1-positive muscle afferents were about 20%. TRPV1-positive primary afferents were contacted with spinal neurons expressing pERK after injection of acetic acid into the muscles. CONCLUSION: It is consequently suggested that nociception from skeletal muscles are mediated by TRPV1-positive primary afferents and majority of them are also peptidergic.

The VR1-Positive Primary Afferent-Mediated Expression of pERK in the Lumbosacral Neurons in Response to Mechanical and Chemical Stimulation of the Urinary Bladder in Rats

OBJECTIVE: This study characterized the neurons in the lumbosacral cord that express phospho ERK (pERK) after distension or irritation of the bladder, and their relation to the vanilloid receptor 1 (VR1) positive primary afferents. METHODS: Mechanical distension and chemical irritation of the bladder were induced by intravesical injection of the saline and mustard oil, respectively. Spinal neurons expressing pERK and the primary afferent fibers were characterized using multiple immunofluorescence for neurokinin 1 (NK1), neuronal nitric oxide synthetase (nNOS) and VR1. RESULTS: Neurons in lamina I, medial dorsal horn (MDH), dorsal gray commissure (DGC) and sacral parasympathetic nucleus (SPN) were immunoreactive for pERK after either mechanical or chemical stimulation. The majority of pERK positive cells were positive for NK1 in lamina I and SPN, but not in the DGC. Most of pERK positive cells are not stained for nNOS except in a small population of the cells in the SPN and DGC. Contacts between perikarya and dendrites of pERK-positive cells and terminals of primary afferents expressing VR1 were identified in lamina I, lateral collateral path (LCP) and SPN. CONCLUSION: In this study, the lumbosacral neurons activated by mechanical and chemical stimulation of the urinary bladder were identified with expression of the pERK, and also provided the evidence that VR1-positive primary afferents may mediate the activation of these neurons.

Change in the Expression of p75 Neurotrophin Receptor and TRPV1 in the Spinal Cord and Dorsal Root Ganglion after an Injury to the Spinal Nerves in Rats / 대한정형외과학회잡지

PURPOSE: To determine the relationship between change in the expression of the p75 neurotrophin receptor (NTR) and transient receptor potential vanilloid 1 (TRPV1) after a spinal nerve injury with time. MATERIALS AND METHODS: The L5 and L6 spinal nerve of the rats were cut unilaterally. The spinal cord and dorsal root ganglion (DRG) were subjected to immunohistochemistry for p75 NTR and TRPV1. RESULTS: The immunoreaction (IR) for p75 NTR in the neuronal cytoplasm was persistently lower on the ipsilateral L5 and L6 DRG but higher in the satellite cells and fibers. The colocalization between p75 NTR and TRPV1 was increased temporarily in the L4 DRG in both sides. In the spinal cord, p75 NTR-IR decreased temporalily in the ipsilateral dorsal horn of the L4-L6 level and had recovered at 28 days after injury. CONCLUSION: These results show that a differential change in the expression of p75 NTR and TRPV1 is related to the different functional recovery of the sensory and motor system, and that increased colocalizations between p75 NTR and TRPV1 in a non-injured DRG might be related to the development of neuropathic pain after a peripheral nerve injury.

Possible Apoptotic Mechanisms in the Vesiculation Process of Pemphigus, Bullous Pemphigoid, and Epidermolysis Bullosa Acquisita / 대한피부과학회지

BACKGROUND: Apoptosis, or programmed cell death, may participate with pathogenesis of intercellular detachment and loss of cell-matrix interaction. Autoimmune bullous dermatoses is an entity charaterized by bullous lesions of the skin and mucosa, and autoantibodies to the specific tissue components. OBJECTIVE: The purpose of this study was to investigate the induction of apoptosis in the lesional skin of pemphigus vulgaris (PV), pemphigus foliaceus (PF), bullous pemphigoid (BP), and epidermolysis bullosa acquisita (EBA). METHODS: Hoechst 33342 (bisbenzimide) staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining was performed to determine the induction of apoptosis in the lesional skin of each disease. RESULTS: In PV and PF, typical findings of apoptosis were observed in the lesional epidermis showing acantholysis. However, in BP and EBA, no apoptosis of the epidermis was observed. CONCLUSION: These results suggest that apoptosis is only associated with acantholysis of the epidermal keratinocytes, one of many components of pathogenesis in bullous disease, in patients with pemphigus.

Effects of 3-aminobenzamide (3-AB) on the alterations in primary afferent and spinal neurons induced by spinal nerve injury in rats / 대한정형외과연구학회지

PURPOSE: The authors studied the effect of the 3-AB, an inhibitor of poly(ADP-ribose)polymerase (PARP), on the changes of primary afferents and spinal cord after spinal nerve injury. METHOD: The L5 and L6 spinal nerve of the rats were cut, and 3-AB (10 mg/Kg) was injected intraperitoneally once per day. The animals were sacrificed 3 days, 7 days, 14 days and 28 days after nerve injury. Binding of isolectin B4 (IB4) and immunohistochemistry (IHC) of CGRP for the changes in primary afferents, IHC of NK1 for sensory neurons, and of cleaved caspase 3 and NeuN for the apoptotic changes in spinal neurons were performed. RESULT: Decreased binding of IB4 and immunoreactivity (IR) for CGRP, increase of IR for NK1, and cleaved caspase 3 in both neurons and glia in ipsilateral dorsal horn were observed after spinal nerve injury. These changes were attenuated, especially at between 3 days and 14 days, by administration of 3-AB. CONCLUSION: It is suggested that inhibition of PARP by 3-AB may attenuate alterations of primary afferents and spinal neurons, at least in early stage, after spinal nerve injury.

Effects of 3-aminobenzamide (3-AB) on the alterations in primary afferent and spinal neurons induced by spinal nerve injury in rats / 대한정형외과연구학회지

PURPOSE: The authors studied the effect of the 3-AB, an inhibitor of poly(ADP-ribose)polymerase (PARP), on the changes of primary afferents and spinal cord after spinal nerve injury. METHOD: The L5 and L6 spinal nerve of the rats were cut, and 3-AB (10 mg/Kg) was injected intraperitoneally once per day. The animals were sacrificed 3 days, 7 days, 14 days and 28 days after nerve injury. Binding of isolectin B4 (IB4) and immunohistochemistry (IHC) of CGRP for the changes in primary afferents, IHC of NK1 for sensory neurons, and of cleaved caspase 3 and NeuN for the apoptotic changes in spinal neurons were performed. RESULT: Decreased binding of IB4 and immunoreactivity (IR) for CGRP, increase of IR for NK1, and cleaved caspase 3 in both neurons and glia in ipsilateral dorsal horn were observed after spinal nerve injury. These changes were attenuated, especially at between 3 days and 14 days, by administration of 3-AB. CONCLUSION: It is suggested that inhibition of PARP by 3-AB may attenuate alterations of primary afferents and spinal neurons, at least in early stage, after spinal nerve injury.