• Archives of Pharmacal Research
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• v.29 no.8
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• pp.699-706
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• 2006

The present study evaluated antioxidant and neuroprotective activities of hesperidin, a flavanone mainly isolated from citrus fruits, and its aglycone hesperetin using cell-free bioassay system and primary cultured rat cortical cells. Both hesperidin and hesperetin exhibited similar patterns of 1,1-diphenyl-2-picrylhydrazyl radical scavenging activities. While hesperidin was inactive, hesperetin was found to be a potent antioxidant, inhibiting lipid peroxidation initiated in rat brain homogenates by $Fe^{2+}$ and L-ascorbic acid. In consistence with these findings, hesperetin protected primary cultured cortical cells against the oxidative neuronal damage induced by $H_2O_2$ or xanthine and xanthine oxidase. In addition, it was shown to attenuate the excitotoxic neuronal damage induced by excess glutamate in the cortical cultures. When the excitotoxicity was induced by the glutamate receptor subtype-selective ligands, only the N-methyl-D-aspartic acid-induced toxicity was selectively and markedly inhibited by hesperetin. Furthermore, hesperetin protected cultured cells against the $A_{{\beta}(25-35)}-induced$ neuronal damage. Hesperidin, however, exerted minimal or no protective effects on the neuronal damage tested in this study. Taken together, these results demonstrate potent antioxidant and neuroprotective effects of hesperetin, implying its potential role in protecting neurons against various types of insults associated with many neurodegenerative diseases.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2006.04a
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• pp.139-149
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• 2006

Amyloid beta (A$\beta$) is believed one of the major pathogens of Alzheimer's disease (AD), and the reduction of A$\beta$ is considered a primary therapeutic target. Immunization with A$\beta$ can reduce A$\beta$ burden and pathological features in transgenic AD model mouse. This means anti-A$\beta$ autoantibodies may have a role in AD pathology. Recent findings suggest anti-A$\beta$ autoantibodies level decrease in AD patients. The early detection of AD is important for treatment of this disease. However, diagnosis on AD has only been possible through limited methods such as neuropsychological examination or MRI. To investigate whether it was possible to detect the presence and different levels of naturally occurring anti-A$\beta$ autoantibodies in the plasma of patients with AD and age-matched controls. An advanced ELISA was performed to detect levels of naturally occurring anti-A$\beta$ autoantibodies in the plasma. The level of anti-A$\beta$ auto-antibodies from patients with idiopathic Parkinson's disease or stroke and from normal controls were compared to that of AD patients. Our results showed a significantly lower anti-A$\beta$ autoantibodies level in AD compared to those with other neurological diseases or control. The level of anti-A$\beta$ autoantibodies in the serum may be used to diagnose the presence of AD.

• Biomolecules & Therapeutics
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• v.15 no.4
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• pp.205-211
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• 2007

The fruits and stems of Opuntia ficus-indica var. saboten have been reported to exhibit a variety of pharmacological actions, including antioxidant, analgesic, anti-inflammatory, and anti-ulcer effects. In the present study, we evaluated effects of the butanol fraction (SK OFB901) prepared from the 50% ethanol extract of the stems on various types of neuronal injuries induced by oxidative stress, excitotoxins, and amyloid ${\beta}\;(A_{\beta})$ in primary cultured rat cortical cells. Its antioxidant and radical scavenging activities were also evaluated by cell-free bioassays. We found that SK OFB901 strongly inhibited the oxidative neuronal damage induced by $H_2O_2$ or xanthine/xanthine oxidase. In addition, it exhibited marked inhibition of the excitotoxic neuronal damage induced by glutamate, N-methyl-D-aspartic acid, or kainate. Furthermore, the $A_{\beta(25-35)}$-induced neurotoxicity was also significantly attenuated by SK OFB901. It was found to inhibit lipid peroxidation initiated by $Fe^{2+}$ and L-ascorbic acid in rat brain homogenates and scavenge 1,1-diphenyl-2-picrylhydrazyl free radicals. These results indicate that the butanol fraction prepared from the stems of Opuntia ficus-indica var. saboten exerts potent antioxidant and neuroprotective effects through multiple mechanisms, implying its potential applications for the prevention or management of neurodegenerative disorders associated with oxidative stress, excitotoxicity, and $A{\beta}$.

• 한국약용작물학회:학술대회논문집
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• 2006.04a
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• pp.137-149
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• 2006

Amyloid beta ($A{\beta}$) is believed one of the major pathogens of Alzheimer's disease (AD), and the reduction of $A{\beta}$ is considered a primary therapeutic target. Immunization with $A{\beta}$ can reduce $A{\beta}$ burden and pathological features in transgenic AD model mouse. This means $anti-A{\beta}$ autoantibodies may have a role in AD pathology. Recent findings suggest $anti-A{\beta}$ autoantibodies level decrease in AD patients. The early detection of AD is important for treatment of this disease. However, diagnosis on AD has only been possible through limited methods such as neuropsychological examination or MRI. To investigate whether it was possible to detect the presence and different levels of naturally occurring $anti-A{\beta}$ autoantibodies in the plasma of patients with AD and age-matched controls. An advanced ELISA was performed to detect levels of naturally occurring $anti-A{\beta}$ autoantibodies in the plasma. The level of $anti-A{\beta}$ auto-antibodies from patients with idiopathic Parkinson's disease or stroke and from normal controls were compared to that of AD patients. Our results showed a significantly lower $anti-A{\beta}$ autoantibodies level in AD compared to those with other neurological diseases or control. The level of $anti-A{\beta}$ autoantibodies in the serum may be used to diagnose the presence of AD.

• Biomolecules & Therapeutics
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• v.22 no.3
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• pp.176-183
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• 2014

Cognitive impairment is a result of dementia of diverse causes, such as cholinergic dysfunction and Alzheimer's disease (AD). Houttuynia cordata Thunb. (Saururaceae) has long been used as a traditional herbal medicine. It has biological activities including protective effects against amyloid beta ($A{\beta}$) toxicity, via regulation of calcium homeostasis, in rat hippocampal cells. To extend previous reports, we investigated the effects of water extracts of H. cordata herb (HCW) on tauopathies, also involving calcium influx. We then confirmed the effects of HCW in improving memory impairment and neuronal damage in mice with Ab-induced neurotoxicity. We also investigated the effects of HCW against scopolamine-induced cholinergic dysfunction in mice. In primary neuronal cells, HCW inhibited the phosphorylation of tau by regulating p25/p35 expression in $A{\beta}$-induced neurotoxicity. In mice with $A{\beta}$-induced neurotoxicity, HCW improved cognitive impairment, as assessed with behavioral tasks, such as novel object recognition, Y-maze, and passive avoidance tasks. HCW also inhibited the degeneration of neurons in the CA3 region of the hippocampus in Ab-induced neurotoxicity. Moreover, HCW, which had an $IC_{50}$ value of $79.7{\mu}g/ml$ for acetylcholinesterase inhibition, ameliorated scopolamine-induced cognitive impairment significantly in Y-maze and passive avoidance tasks. These results indicate that HCW improved cognitive impairment, due to cholinergic dysfunction, with inhibitory effects against tauopathies and cholinergic antagonists, suggesting that HCW may be an interesting candidate to investigate for the treatment of AD.

• The Korean Journal of Pain
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• v.36 no.1
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• pp.11-50
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• 2023

As the field of interventional pain management (IPM) grows, the risk of surgical site infections (SSIs) is increasing. SSI is defined as an infection of the incision or organ/space that occurs within one month after operation or three months after implantation. It is also common to find patients with suspected infection in an outpatient clinic. The most frequent IPM procedures are performed in the spine. Even though primary pyogenic spondylodiscitis via hematogenous spread is the most common type among spinal infections, secondary spinal infections from direct inoculation should be monitored after IPM procedures. Various preventive guidelines for SSI have been published. Cefazolin, followed by vancomycin, is the most commonly used surgical antibiotic prophylaxis in IPM. Diagnosis of SSI is confirmed by purulent discharge, isolation of causative organisms, pain/tenderness, swelling, redness, or heat, or diagnosis by a surgeon or attending physician. Inflammatory markers include traditional (C-reactive protein, erythrocyte sedimentation rate, and white blood cell count) and novel (procalcitonin, serum amyloid A, and presepsin) markers. Empirical antibiotic therapy is defined as the initial administration of antibiotics within at least 24 hours prior to the results of blood culture and antibiotic susceptibility testing. Definitive antibiotic therapy is initiated based on the above culture and testing. Combination antibiotic therapy for multidrug-resistant Gram-negative bacteria infections appears to be superior to monotherapy in mortality with the risk of increasing antibiotic resistance rates. The never-ending war between bacterial resistance and new antibiotics is continuing. This article reviews prevention, diagnosis, and treatment of infection in pain medicine.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.2
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• pp.374-380
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• 2009

Samryungbaikchul-san(SRBCS) has been used in oriental medicine for the treatments of gastrointestinal and neurological disorders. Here, potential protective function of SRBCS was investigated in neural tissues in Alzheimer's disease(AD) mouse model. In primary cultured cells from the spinal cord of newborn rats, treatment of ${\beta}$-amyloid peptide elevated cell counts positive to glial fibrillary acidic protein(GFAP) or caspase 3 immunoreactivity, but the co-treatment of SRBCS reduced positive cell counts. In vivo administration of scopolamine, an inhibitor of muscarinic receptor, resulted in increases in the number of glial fibrillary acidic protein(GFAP) and caspase 3-positive cells in hippocampal subfields, which was then decreased by the treatment of SRBCS or acetylcholinesterase inhibitor galathamine. The present data suggest that SRBCS may play a protective role in damaged neural tissues caused by scopolamine treatments in mice.

• Journal of Life Science
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• v.21 no.5
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• pp.647-655
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• 2011

The neurotoxicity of aggregated amyloid ${\beta}$ ($A{\beta}$) has been implicated as a critical cause in the pathogenesis of Alzheimer's disease (AD). It can cause neurotoxicity in AD by evoking a cascade of apoptosis to neuron. Here, we investigated the neuroprotective effects of cilostazol, which acts as a phosphodiesterase III inhibitor, on $A{\beta}_{25-35}$-induced cytotoxicity in mouse neuronal cells and cognitive decline in the C57BL/6J AD mouse model via peroxisome proliferator-activated receptor (PPAR)-${\gamma}$ activation. $A{\beta}_{25-35}$ significantly reduced cell viability and increased the number of apoptotic-like cells. Cilostazol treatment recovered cells from $A{\beta}$-induced cell death as well as rosiglitazone, a PPAR-${\gamma}$ activator. These effects were suppressed by GW9662, an antagonist of PPAR-${\gamma}$ activity, indicative of a PPAR-${\gamma}$-mediated signaling. In addition, cilostazol and rosiglitazone also restored PPAR-${\gamma}$ activity levels that had been altered as a result of $A{\beta}_{25-35}$ treatment, which were antagonized by GW9662. Furthermore, cilostazol also markedly decreased the number of apoptotic-like cells and decreased the Bax/Bcl-2 ratio. Intracerebroventricular injection of $A{\beta}_{25-35}$ in C57BL/6J mice resulted in impaired cognitive function. Oral administration of cilostazol (20 mg/kg) for 2 weeks before $A{\beta}_{25-35}$ injection and once a day for 4 weeks post-surgery almost completely prevented the $A{\beta}_{25-35}$-induced cognitive deficits, as did rosiglitazone. Taken together, our findings suggest that cilostazol could attenuate $A{\beta}_{25-35}$-induced neuronal cell injury and apoptosis as well as promote the survival of neuronal cells, subsequently improving cognitive decline in AD, partly because of PPAR-${\gamma}$ activation. The phosphodiesterase III inhibitor cilostazol may be the basis of a novel strategy for the therapy of AD.

• Tuberculosis and Respiratory Diseases
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• v.49 no.3
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• pp.365-371
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• 2000

Nodular pulmonary amyloidosis is one of the rare manifestation of amyloid disease. It is known to be caused by amyloid L fibrils in the majority of cases. We experienced an unusual case of a forty-one year-old woman who was presented with multiple nodular lesion on the chest X-ray. CT-guided core needle biopsy, performed on the lesion, showed apple green birefringes, when stained Congo red and examined under polarized light, Ultrastructurally, there are randomly oriented, forming densed networks, and consists of fine, 7.5 to 10nm diameter, rigid, non-branching filaments of various lengths in electron-microscopic finding. We report a case of primary diffuse nodular pulmonary amyloidosis only localized in the lung, which was confirmed by CT guided core needle biopsy.

• Tuberculosis and Respiratory Diseases
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• v.52 no.2
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• pp.174-178
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• 2002

Primary pulmonary amyloidosis is a rare condition that can be classified into the tracheobronchial, diffuse alveolar septal, and nodular parenchymal type. Tracheobronchial amyloidosis is characterized by deposition of fibrilar proteins in the tracheobronchial tree, and it can be subdivided into diffuse and focal varieties. In this report, a case of diffuse tracheobronchial amyloidosis confirmed by flexible fiberoptic bronchoscopic biopsy is presented. The patient was a 43-year old male with a chief complaint of cough and sputum for 20 days and dyspnea for one day. The chest CT scan showed diffusely thickened walls of both the main and lobar bronchi with calcification. The bronchoscopic findings showed nodular lesions of the trachea, a diffuse bronchial stenosis of both the main bronchi and a pinpoint narrowing of the left upper and right middle lobar bronchus. The biopsy showed submucosal deposits of homogenous eosinophilic amyloid materials and an apple-green birefringence under polarizing microscopy following the Congo-red stain.