Extracellular vesicles (EVs), such as exosomes and microvesicles, are cell-derived lipid bilayer membrane particles, which deliver information from host cells to recipient cells. EVs are involved in various biological processes including the modulation of the immune response, cell-to-cell communications, thrombosis, and tissue regeneration. Different types of kidney cells are known to release EVs under physiologic as well as pathologic conditions, and recent studies have found that EVs have a pathophysiologic role in different renal diseases. Given the recent advancement in EV isolation and analysis techniques, many studies have shown the diagnostic and therapeutic potential of EVs in various renal diseases, such as acute kidney injury, polycystic kidney disease, chronic kidney disease, kidney transplantation, and renal cell carcinoma. This review updates recent clinical and experimental findings on the role of EVs in renal diseases and highlights the potential clinical applicability of EVs as novel diagnostics and therapeutics.

Extracellular vesicles (EVs), such as exosomes and microvesicles, are cell-derived lipid bilayer membrane particles, which deliver information from host cells to recipient cells. EVs are involved in various biological processes including the modulation of the immune response, cell-to-cell communications, thrombosis, and tissue regeneration. Different types of kidney cells are known to release EVs under physiologic as well as pathologic conditions, and recent studies have found that EVs have a pathophysiologic role in different renal diseases. Given the recent advancement in EV isolation and analysis techniques, many studies have shown the diagnostic and therapeutic potential of EVs in various renal diseases, such as acute kidney injury, polycystic kidney disease, chronic kidney disease, kidney transplantation, and renal cell carcinoma. This review updates recent clinical and experimental findings on the role of EVs in renal diseases and highlights the potential clinical applicability of EVs as novel diagnostics and therapeutics.

BACKGROUND AND PURPOSE: Discrepancies between objectively measured sleep and subjective sleep perception in patients with insomnia have been reported. However, few studies have investigated sleep-state misperception in patients with obstructive sleep apnea (OSA). We designed this study to 1) delineate the factors that could affect this discrepancy and 2) infer an underlying mechanism in patients with OSA. METHODS: We recruited patients who visited our sleep clinic for the evaluation of their snoring and/or observed OSA. Participants completed a structured questionnaire and underwent overnight polysomnography. On the following day, five sessions of the multiple sleep latency test (MSLT) were applied. We divided the patients into two groups: normal sleep perception and abnormal perception. The abnormal-perception group included patients whose perceived total sleep time was less than 80% of that measured in polysomnography. RESULTS: Fifty OSA patients were enrolled from a university hospital sleep clinic. Excessive daytime sleepiness, periodic limb movement index (PLMI), and the presence of dreaming were positively associated with poor sleep perception. REM sleep near the sleep termination exerted important effects. Respiratory disturbance parameters were not related to sleep perception. There was a prolongation in the sleep latency in the first session of the MSLT and we suspected that a delayed sleep phase occurred in poor-sleep perceivers. CONCLUSIONS: As an objectively good sleep does not match the subjective good-sleep perception in OSA, physicians should keep in mind that OSA patients who perceive that they have slept well does not mean that their OSA is less severe.
Dreams ; Extremities ; Humans ; Polysomnography* ; Sleep Apnea, Obstructive* ; Sleep Initiation and Maintenance Disorders ; Sleep, REM ; Snoring

Stroke is one of the common causes of death and disability. Despite extensive efforts in stroke research, therapeutic options for improving the functional recovery remain limited in clinical practice. Experimental stroke models using genetically modified mice could aid in unraveling the complex pathophysiology triggered by ischemic brain injury. Here, we optimized the procedure for generating mouse stroke model using an intraluminal suture in the middle cerebral artery and verified the blockage of blood flow using indocyanine green coupled with near infra-red radiation. The first week after the ischemic injury was critical for survivability. The survival rate of 11% in mice without any treatment but increased to 60% on administering prophylactic antibiotics. During this period, mice showed severe functional impairment but recovered spontaneously starting from the second week onward. Among the various behavioral tests, the pole tests and neurological severity score tests remained reliable up to 4 weeks after ischemia, whereas the rotarod and corner tests became less sensitive for assessing the severity of ischemic injury with time. Further, loss of body weight was also observed for up 4 weeks after ischemia induction. In conclusion, we have developed an improved approach which allows us to investigate the role of the cell death-related genes in the disease progression using genetically modified mice and to evaluate the modes of action of candidate drugs.
Animals ; Anti-Bacterial Agents ; Body Weight ; Brain Injuries ; Brain Ischemia ; Cause of Death ; Disease Progression ; Indocyanine Green ; Ischemia ; Mice* ; Middle Cerebral Artery ; Stroke* ; Survival Rate ; Sutures ; Therapeutic Human Experimentation

We correct a typo in the title.

It is well established that excessive sodium intake is related to a higher incidence of chronic diseases such as hypertension, stroke, coronary heart disease, cardiovascular disease and gastric cancer. Although the upper limit of the current sodium intake guideline by WHO is set at 2,000 mg/day for adults, sodium intake of Koreans is well over 4,700 mg/capita/day implying an urgent need to develop and implement sodium intake reduction policy at the national level. This study investigated the cost-effectiveness of the sodium intake reduction policy, for the first time, in Korea. Analyses were performed using most recent and representative data on national health insurance statistics, healthcare utilization, employment information, disease morbidity/mortality, etc. The socioeconomic benefits of the policy, resulting from reduced morbidity of those relevant diseases, included lower medical expenditures, transportation costs, caregiver cost for inpatients and income losses. The socioeconomic benefits from diminished mortality included reductions in earning losses and welfare losses caused by early deaths. It is estimated that the amount of total benefits of reducing sodium intake from 4.7 g to 3.0 g is 12.6 trillion Korean Won; and the size of its cost is 149 billion Won. Assuming that the effect of sodium intake reduction would become gradually evident over a 5-year period, the implied rate of average return to the sodium reduction policy is 7,790% for the following 25 years, suggesting a very high cost-effectiveness. Accordingly, development and implementation of a mid-to-long term plan for a consistent sodium intake reduction policy is extremely beneficial and well warranted.
Adult ; Cardiovascular Diseases ; Caregivers ; Chronic Disease ; Coronary Disease ; Cost-Benefit Analysis ; Delivery of Health Care ; Employment ; Health Expenditures ; Humans ; Hypertension ; Incidence ; Inpatients ; Korea ; National Health Programs ; Sodium ; Stomach Neoplasms ; Stroke ; Transportation

PURPOSE: Current treatment of glioblastoma after surgery consists of a combination of fractionated radiotherapy and temozolomide. However, it is difficult to completely remove glioblastoma because it has uncertain boundaries with surrounding tissues. Moreover, combination therapy is not always successful because glioblastoma has diverse resistances. To overcome these limitations, we examined the combined effects of chemotherapy and knockdown of mitogen-activated protein kinase phosphatase-1 (MKP-1). MATERIALS AND METHODS: We used ten different anti-cancer drugs (cisplatin, cyclophosphoamide, doxorubicin, epirubicin, etoposide, 5-fluorouracil, gemcitabine, irinotecan, mitomycin C, and vincristine) to treat glioblastoma multiforme (GBM) cells. Knockdown of MKP-1 was performed using siRNA and lipofectamine. The basal level of MKP-1 in GBM was analyzed based on cDNA microarray data obtained from the Gene Expression Omnibus (GEO) databases. RESULTS: Anti-cancer drug-induced cell death was significantly enhanced by knockdown of MKP-1, and this effect was most prominent in cells treated with irinotecan and etoposide. Treatment with these two drugs led to significantly increased phosphorylation of c-Jun N-terminal kinase (JNK) in a time-dependent manner, while pharmacological inhibition of JNK partially inhibited drug-induced cell death. Knockdown of MKP-1 also enhanced drug-induced phosphorylation of JNK. CONCLUSION: Increased MKP-1 expression levels could be the cause of the high resistance to conventional chemotherapeutics in human GBM. Therefore, MKP-1 is an attractive target for overcoming drug resistance in this highly refractory malignancy.
Apoptosis ; Camptothecin ; Cell Death ; Dacarbazine ; Deoxycytidine ; Doxorubicin ; Drug Resistance ; Drug Resistance, Multiple ; Dual Specificity Phosphatase 1 ; Epirubicin ; Etoposide ; Fluorouracil ; Gene Expression ; Glioblastoma ; Humans ; JNK Mitogen-Activated Protein Kinases ; Lipids ; Mitomycin ; Oligonucleotide Array Sequence Analysis ; Phosphorylation ; Phosphotransferases ; Protein Kinases ; RNA, Small Interfering

Brown tumors are erosive bony lesions caused by the chronic excessive secretion of parathyroid hormone. Since the introduction of routine calcium measurement, the diagnosis of hyperparathyroidism has usually been made in asymptomatic patients, and as a result, brown tumors are rarely observed as an initial manifestation of hyperparathyroidism. The authors report a case of a 32-year-old woman who presented with right cheek swelling. A CT scan showed erosive bone tumors of the mandible. These lesions were finally diagnosed as brown tumors associated with secondary hyperparathyroidism due to chronic renal failure. Brown tumor as a result of hyperparathyroidism is a relatively rare clinical finding in otorhinolaryngology, thus, the authors illustrate this case with a brief review of the literature.
Adult ; Calcium ; Cheek ; Female ; Humans ; Hyperparathyroidism ; Hyperparathyroidism, Secondary ; Kidney Failure, Chronic ; Mandible ; Otolaryngology ; Parathyroid Hormone

OBJECTIVES: To examine possible modulators of the ion transport through the apical membrane of the nasal polyps. METHODS: The study was conducted using the freshly-excised nasal polyps from the patients with chronic sinusitis. A voltage-sensitive vibrating probe technique was introduced to monitor the short-circuit current across the apical membrane of the polyp at 37degrees C. RESULTS: In the presence of amiloride, Adenosine 5'-triphosphate induced 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic acidsensitive chloride current. Uridine 5'-diphosphate was less potent than Uridine 5'-triphosphate, and adenosine increased chloride secretion, which was blocked by the antagonist, 8-(p-sulfophenyl) theophylline on adenosine receptor. Based on the pharmacologic profiles, multiple purinergic receptors, including P2Y(2), P2Y(6), and P1 receptors, were functionally expressed. However, P2X receptor agonists (alpha,beta-methyleneadenosine 5'-triphosphate and 2'- & 3'-O-[4-benzoyl-benzoyl] adenosine 5'-triphosphate), Cystic fibrosis conductance regulator (CFTR) activator (genistein), nitric oxide substrate (L-arginine), and nitric oxide donor (sodium nitroprusside) had no significant effect on the short circuit current. CONCLUSION: Among tested drugs, P2Y receptor agonists were major modulators of ion transport in nasal polyps in situ.
Adenosine ; Amiloride ; Cystic Fibrosis ; Genistein ; Humans ; Ion Transport ; Membranes ; Nasal Polyps ; Nitric Oxide ; Organothiophosphorus Compounds ; Polyps ; Receptors, Purinergic ; Receptors, Purinergic P1 ; Sinusitis ; Theophylline ; Tissue Donors ; Uridine

Background and purpose: The availability and promise of effective treatments for neurodegenerative disorders are increasing the importance of early diagnosis. Having molecular and biochemical markers of Alzheimer's disease (AD) would complement clinical approaches, and further the goals of early and accurate diagnosis. Combining multiple biomarkers in evaluations significantly increases the sensitivity and specificity of the biochemical tests. Methods: In this study, we used color-coded bead-based Luminex technology to test the potential of using chemokines and cytokines as biochemical markers of AD. We measured the levels of 22 chemokines and cytokines in the serum and cerebrospinal fluid (CSF) of 32 de novo patients (13 controls, 11 AD, and 8 Parkinson's disease [PD]). Results: MCP-1 was the only cytokine detectable in CSF, and its levels did not differ between control and disease groups. However, the serum concentration of eotaxin was significantly higher in AD patients than in the control group. Conclusions: The analysis of multiple inflammatory mediators revealed marginal differences in their CSF and serum concentrations for the differential diagnosis of AD and PD. These results provide evidence that immunological responses are not major contributors to the pathogenesis of AD and PD.
Alzheimer Disease ; Biomarkers ; Chemokines ; Complement System Proteins ; Cytokines ; Diagnosis, Differential ; Early Diagnosis ; Humans ; Neurodegenerative Diseases ; Parkinson Disease ; Sensitivity and Specificity