ABSTRACT
Myoblast fusion depends on mitochondrial integrity and intracellular Ca²⁺ signaling regulated by various ion channels. In this study, we investigated the ionic currents associated with [Ca²⁺]i regulation in normal and mitochondrial DNA-depleted (ρ0) L6 myoblasts. The ρ0 myoblasts showed impaired myotube formation. The inwardly rectifying K⁺ current (I(Kir)) was largely decreased with reduced expression of KIR2.1, whereas the voltage-operated Ca²⁺ channel and Ca²⁺-activated K⁺ channel currents were intact. Sustained inhibition of mitochondrial electron transport by antimycin A treatment (24 h) also decreased the I(Kir). The ρ0 myoblasts showed depolarized resting membrane potential and higher basal [Ca²⁺]ᵢ. Our results demonstrated the specific downregulation of I(Kir) by dysfunctional mitochondria. The resultant depolarization and altered Ca²⁺ signaling might be associated with impaired myoblast fusion in ρ0 myoblasts.
Subject(s)
Antimycin A , Down-Regulation , Electron Transport , Ion Channels , Membrane Potentials , Mitochondria , Muscle Development , Muscle Fibers, Skeletal , Myoblasts , Oxidative PhosphorylationABSTRACT
Transient receptor potential vanilloid 3 (TRPV3) is a non-selective cation channel with modest permeability to calcium ions. It is involved in intracellular calcium signaling and is therefore important in processes such as thermal sensation, skin barrier formation, and wound healing. TRPV3 was initially proposed as a warm temperature sensor. It is activated by synthetic small-molecule chemicals and plant-derived natural compounds such as camphor and eugenol. Schisandra chinensis (Turcz.) Baill (SC) has diverse pharmacological properties including antiallergic, anti-inflammatory, and wound healing activities. It is extensively used as an oriental herbal medicine for the treatment of various diseases. In this study, we investigated whether SC fruit extracts and seed oil, as well as four compounds isolated from the fruit can activate the TRPV3 channel. By performing whole-cell patch clamp recording in HEK293T cells overexpressing TRPV3, we found that the methanolic extract of SC fruit has an agonistic effect on the TRPV3 channel. Furthermore, electrophysiological analysis revealed that γ-schisandrin, one of the isolated compounds, activated TRPV3 at a concentration of 30 µM. In addition, γ-schisandrin (~100 µM) increased cytoplasmic Ca²⁺ concentrations by approximately 20% in response to TRPV3 activation. This is the first report to indicate that SC extract and γ-schisandrin can modulate the TRPV3 channel. This report also suggests a mechanism by which γ-schisandrin acts as a therapeutic agent against TRPV3-related diseases.
Subject(s)
Calcium , Calcium Channels , Calcium Signaling , Camphor , Cytoplasm , Eugenol , Fruit , Herbal Medicine , Ions , Methanol , Permeability , Schisandra , Sensation , Skin , Wound HealingABSTRACT
PURPOSE: This study was planned to evaluate that a lecture employing medical drama could motivate students to have an interest in the professionalism of healthcare personnel, which has currently become a critical subject in the field of medical education. METHODS: We analyzed subject headings, learning objectives, and further plans developed by students and their responses after two drama modules, 'car crash' and 'refusal of instruction', which were selected based on the conditions made by our faculty members, were given through video or paper to our 121 second-grade medical and nursing students in year 2012. RESULTS: Meaningful subject headings and learning objectives developed by students were 58.2%~60.0% and 36.8%~38.0% and significantly more in the 'refusal of instruction' than the 'car crash' (p=0.000). According to the students' major, medical students developed significantly more than nursing students (p=0.000). In the analysis of responses, 91.7% of students reported as impressive to the educational modules and 55.3% of them described their ideas associated with healthcare professionalism. CONCLUSION: Our study results suggest a possibility that the educational module employing selected medical drama could motivate students' healthcare professionalism.
Subject(s)
Humans , Delivery of Health Care , Drama , Learning , Students, Medical , Students, Nursing , Subject HeadingsABSTRACT
BACKGROUND AND OBJECTIVES: Pulmonary arterial hypertension (PAH) is a life threatening disease characterized by progressive pulmonary arterial occlusion which may ultimately result in death. Currently, the available treatments are diverse, but no therapy alone can reverse the disease process although they may have some clinical benefits. This study was designed to investigate single and combination therapy of simvastatin and sildenafil, which have different mechanisms of action, in monocrotaline (MCT)-induced PAH. METERIALS AND METHODS: Rats were randomized to receive saline (control, n=8) or MCT treatment (n=32). MCT treated rats were randomized to vehicle, simvastatin (2 mg/kg/day), sildenafil (25 mg/kg/day) and a combination simvastatin and sildenafil (n=8, respectively). Three weeks later, hemodynamic study and histologic changes of pulmonary arterioles were measured. Proliferating cell nuclear antigen (PCNA) as well as Western blot for endothelial nitric oxide synthase (eNOS) were performed. RESULTS: Systolic right ventricular pressure was significantly decreased in monotherapy groups (simvastatin and sildenafil) and the combination group compared to MCT group (p<0.05). Right ventricular hypertrophy and medial wall thickness of pulmonary arterioles were significantly attenuated with sole and combination therapy (p<0.05). However, combination therapy did not confer additive benefits over monotherapy. Altered PCNA or eNOS in lung tissue was normalized by either monotherapy or combination therapy. CONCLUSION: The results suggest that either simvastatin or sildenafil has the therapeutic potential in MCT-induced PAH, although combination therapy of these two drugs has failed to show greater benefits in the study.
Subject(s)
Animals , Rats , Arterioles , Blotting, Western , Hemodynamics , Hypertension , Hypertension, Pulmonary , Hypertrophy, Right Ventricular , Lung , Monocrotaline , Nitric Oxide Synthase Type III , Piperazines , Proliferating Cell Nuclear Antigen , Pulmonary Circulation , Purines , Simvastatin , Sulfones , Ventricular Pressure , Sildenafil CitrateABSTRACT
The systolic and diastolic pressures in anesthetized Sprague-Dawley male rats were greatly decreased after single-dose of Cd treatment without significant changes in heart rate. There was a fluid-shift into the third space and/or -loss through the kidney, since plasma Na+ concentration and hematocrit ratio were significantly increased by acute Cd exposure. The present study showed that the sustained hypotensive effect of single-dose Cd on the cardiovascular system might have resulted from the systemic hypovolemia. Furthermore, renal excretion of electrolytes, including Na+ and K+, and urine flow rate were increased by Cd intoxication. Interestingly, the ratio of Na+/K+ excretion was increased and reached the maximum level 3 hours after Cd injection and returned to the normal level after 7 hours. Nevertheless, there was no difference in the regression analysis of K+ excretion and urine flow rate in both groups. Therefore, the increase in the urine volume seemed to enhance the excretion of K+. This study strongly suggest that the hypotensive effect of Cd is mediated by systemic Na+ loss through the kidney and/or hypovolemia via fluid-shift.
Subject(s)
Animals , Humans , Male , Rats , Cadmium , Cardiovascular System , Electrolytes , Heart Rate , Hematocrit , Hemodynamics , Hypovolemia , Kidney , Plasma , Rats, Sprague-DawleyABSTRACT
Na+/H+ exchanger (NHE) has a critical role in regulation of intracellular pH (pHi) in the renal proximal tubular cells. It has recently been shown that dopamine inhibits NHE in the renal proximal tubules. Nevertheless, there is a dearth of information on the effects of long-term (chronic) dopamine treatment on NHE activities. This study was performed to elucidate the pHi regulatory mechanisms during the chronic dopamine treatments in renal proximal tubular OK cells. The resting pHi was greatly decreased by chronic dopamine treatments. The initial rate and the amplitude of intracellular acidification by isosmotical Na+ removal from the bath medium in chronically dopamine-treated cells were much smaller than those in control. Although it seemed to be attenuated in Na+-dependent pH regulation system, Na+-dependent pHi recovery by NHE after intracelluar acid loading in the dopamine-treated groups was not significantly different from the control. The result is interpreted to be due to the balance between the stimulation effects of lower pHi on the NHE activity and counterbalance by dopamine. Our data strongly suggested that chronic dopamine treatment increased intrinsic intracellular buffer capacity, since higher buffer capacity was induced by lower resting pHi and this effect could attenuate pHi changes under extracellular Na+-free conditions in chronically dopamine-treated cells. Our study also demonstrated that intracellular acidification induced by chronic dopamine treatments was not mediated by changes in NHE activity.
Subject(s)
Baths , Dopamine , Hydrogen-Ion Concentration , Kidney , OpossumsABSTRACT
In the present studies, changes of the glial fibrillary acidic protein (GFAP) expression in the astrocytes of the rat hippocampal formation were examined in response to the bilateral carotid artery occlusion for 10 minutes along with a decrease of mean arterial blood pressure (MABP) to 50 mmHg. Their relations to neuronal viability were also studied by H&E staining. In early postischemic period, mild increase of the GFAP expression was observed and this was not only confined to the mild-necrotic (CA3 and dentate gyrus) regions but also in the non-necrotic regions (CA1 and subiculum) at postischemic 8 h. This suggest that astrocytosis during early postischemic period may be resulted from nonspecific reaction associated with changes in brain environment. In contrast, in late phase of the postischemia, a marked increase of the GFAP expression was observed at day 4. Moreover, cell bodies were significantly larger and many prominent and numerous processes were observed, suggesting that this may also contribute to the significant increase in the GFAP expression. Importantly, these cellular changes were only confined to the regions of massive necrosis such as subiculum and inner granular cell layer of dentate gyrus and were not observed in the non-necrotic regions (except CA1). In contrast, the GFAP expression in astrocytes were returned to control levels in mildly damaged CA3 region by 4 days. Thus reactive astrocytosis with upregulation of the GFAP in the late postischemic period with structural transformation in the regions of massive necrosis may contribute to the damages in the neighboring neurons.
Subject(s)
Animals , Rats , Arterial Pressure , Astrocytes , Brain , Carotid Arteries , Dentate Gyrus , Glial Fibrillary Acidic Protein , Gliosis , Hippocampus , Necrosis , Neurons , Up-RegulationABSTRACT
Effects of cadmium exposure on renal Na+ and K+ transports were studied in rats. During the course of cadmium treatment (2 mg Cd/kg/day, s.c. injections for 3 weeks) renal tubular transports of Na+ and K+ were evaluated by lithium clearance technique. During the early phase (first week) of cadmium treatment, urinary Na+ excretion decreased drastically and this was due to an increased Na+ reabsorption both in the proximal and distal nephrons. During the late phase (third week) of cadmium treatment, filtered Na+ load was decreased by reduction in GFR, but the renal Na+ excretion returned to the control level due to impaired Na+ transport in the proximal tubule. Urinary excretion of K+ did not change during the early phase, but it rose markedly during the late phase of cadmium treatment. These results indicate that a light cadmium intoxication induces a Na+ retention, and a heavy intoxication results in a K+ loss. Possible mechanisms for these changes are discussed.
Subject(s)
Animals , Rats , Cadmium , Lithium , Nephrons , Potassium , SodiumABSTRACT
A case of Lichen planus in 41 year old with predisposing emotional factor is reported here and reviewed therapeutic experiences and reveiwed of literatures. This patient who has been suffering from pruritic, dull erythematous maculo-papular eruptions of trunk and extremites which was preoccupied with imagination as if she were exposed sequela to atomic bomb explosion in Japan, World War II, is presented.
Subject(s)
Adult , Humans , Explosions , Fibrinogen , Imagination , Japan , Lichen Planus , Lichens , Nuclear Weapons , World War IIABSTRACT
The one case of sparganosis is described, the patient, 45 years old male, had adult fist sized tumor mass on scrotum for 3 year's duration and removed 4 adults sparganum mansonoides by surgical operation. Attention is calIed to the importance of sparganosis in subcutaneous swelling or tumor because of to took lived snake or non-boiling water in customary at Korea.
Subject(s)
Adult , Humans , Male , Middle Aged , Korea , Scrotum , Snakes , Sparganosis , Sparganum , WaterABSTRACT
The one case of sparganosis is described, the patient, 45 years old male, had adult fist sized tumor mass on scrotum for 3 year's duration and removed 4 adults sparganum mansonoides by surgical operation. Attention is calIed to the importance of sparganosis in subcutaneous swelling or tumor because of to took lived snake or non-boiling water in customary at Korea.
Subject(s)
Adult , Humans , Male , Middle Aged , Korea , Scrotum , Snakes , Sparganosis , Sparganum , WaterABSTRACT
Two cases of xeroderma pigmentosum in brothers without complicated by malignant changes were presented. The clinical and histopathological studies revealed characteristic features of the disease and literatures reviewed.
Subject(s)
Humans , Ichthyosis , Siblings , Xeroderma PigmentosumABSTRACT
Two cases of xeroderma pigmentosum in brothers without complicated by malignant changes were presented. The clinical and histopathological studies revealed characteristic features of the disease and literatures reviewed.