Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

Peripheral neurodegenerative diseases induced by irreversible peripheral nerve degeneration (PND), such as diabetic peripheral neuropathy, have a high prevalence worldwide and reduce the quality of life. However, there is no agent effective against the irreversible PND. After peripheral nerve injury, Schwann cells play an important role in regulating PND. However, because PND involves multiple biochemical events in Schwann cells, a one-drug-single-target therapeutic strategy is not feasible for PND. Here, we suggested that fascaplysin (Fas), a compound with multiple targets (CDK4/6), could overcome these problems. Fas exerted a significant inhibitory effect on axonal degradation, demyelination, and Schwann cell proliferation and dedifferentiation during in vitro and ex vivo PND. To discover the most likely novel target for PND, a chemo-bioinformatics analysis predicted the other on-targets of Fas and identified androgen receptor (AR) which were involved in Schwann cell differentiation and proliferation.AR interacted with Fas, and nuclear import of the AR/Fas complex was inhibited in Schwann cells, altering the expression patterns of transcription factors during PND. Therefore, Fas may have therapeutic potential for irreversible peripheral neurodegenerative diseases.

BACKGROUND: Intima-media thickness (IMT) of the carotid arteries is known to have a positive correlation with the risk of cardiovascular disease. This study was designed to identify risk factors affecting the progression of carotid IMT in patients with type 2 diabetes mellitus (T2DM). METHODS: Patients with newly diagnosed T2DM with carotid IMT measurements were enrolled, and their clinical data and carotid IMT results at baseline and 2 years later were compared. RESULTS: Of the 171 patients, 67.2% of males and 50.8% of females had abnormal baseline IMT of the left common carotid artery. At baseline, systolic blood pressure, body mass index and smoking in male participants, and fasting plasma glucose and glycated hemoglobin levels in females were significantly higher in patients with abnormal IMT than in those with normal IMT. Low density lipoprotein cholesterol (LDL-C) levels in males and high density lipoprotein cholesterol (HDL-C) levels in females at the 2-year follow-up were significantly different between the nonprogression and the progression groups. Reduction of the United Kingdom Prospective Diabetes Study (UKPDS) 10-year coronary heart disease (CHD) risk score after 2 years was generally higher in the nonprogression group than the progression group. CONCLUSION: LDL-C levels in males and HDL-C levels in females at the 2-year follow-up were significantly different between participants with and without progression of carotid IMT. Furthermore, a reduction in the UKPDS 10-year CHD risk score appeared to delay the advancement of atherosclerosis. Therefore, the importance of establishing the therapeutic goal of lipid profiles should be emphasized to prevent the progression of carotid IMT in newly diagnosed T2DM patients.
Atherosclerosis ; Blood Pressure ; Blood Glucose ; Body Mass Index ; Cardiovascular Diseases ; Carotid Arteries ; Carotid Artery, Common ; Cholesterol ; Cholesterol, HDL ; Cholesterol, LDL ; Coronary Disease ; Diabetes Mellitus, Type 2 ; Fasting ; Female ; Follow-Up Studies* ; Hemoglobin A, Glycosylated ; Humans ; Lipoproteins ; Male ; Risk Factors* ; Smoking

BACKGROUND: Intima-media thickness (IMT) of the carotid arteries is known to have a positive correlation with the risk of cardiovascular disease. This study was designed to identify risk factors affecting the progression of carotid IMT in patients with type 2 diabetes mellitus (T2DM). METHODS: Patients with newly diagnosed T2DM with carotid IMT measurements were enrolled, and their clinical data and carotid IMT results at baseline and 2 years later were compared. RESULTS: Of the 171 patients, 67.2% of males and 50.8% of females had abnormal baseline IMT of the left common carotid artery. At baseline, systolic blood pressure, body mass index and smoking in male participants, and fasting plasma glucose and glycated hemoglobin levels in females were significantly higher in patients with abnormal IMT than in those with normal IMT. Low density lipoprotein cholesterol (LDL-C) levels in males and high density lipoprotein cholesterol (HDL-C) levels in females at the 2-year follow-up were significantly different between the nonprogression and the progression groups. Reduction of the United Kingdom Prospective Diabetes Study (UKPDS) 10-year coronary heart disease (CHD) risk score after 2 years was generally higher in the nonprogression group than the progression group. CONCLUSION: LDL-C levels in males and HDL-C levels in females at the 2-year follow-up were significantly different between participants with and without progression of carotid IMT. Furthermore, a reduction in the UKPDS 10-year CHD risk score appeared to delay the advancement of atherosclerosis. Therefore, the importance of establishing the therapeutic goal of lipid profiles should be emphasized to prevent the progression of carotid IMT in newly diagnosed T2DM patients.
Atherosclerosis ; Blood Pressure ; Blood Glucose ; Body Mass Index ; Cardiovascular Diseases ; Carotid Arteries ; Carotid Artery, Common ; Cholesterol ; Cholesterol, HDL ; Cholesterol, LDL ; Coronary Disease ; Diabetes Mellitus, Type 2 ; Fasting ; Female ; Follow-Up Studies* ; Hemoglobin A, Glycosylated ; Humans ; Lipoproteins ; Male ; Risk Factors* ; Smoking

Coinfection with herpes simplex virus and cytomegalovirus is a very rare cause of esophageal ulcer and upper gastrointestinal hemorrhage. A 26 year-old male kidney transplant recipient was referred with a complaint of melena. Upper gastrointestinal endoscopy showed a huge esophageal ulcer in the anastomosis site of the esophagogastrostomy. The ulcer occupied about two-thirds of the circumference of the esophageal lumen and an exposed vessel in the ulcer base was noted. Pathologic findings with immunohistochemical stain showed co-infection of herpes simplex virus and cytomegalovirus. He was treated successfully with endoscopic hemostasis and antiviral therapy. We report a case of upper gastrointestinal hemorrhage from esophageal ulcer caused by coinfection of herpes simplex virus and cytomegalovirus.
Coinfection ; Cytomegalovirus ; Endoscopy, Gastrointestinal ; Gastrointestinal Hemorrhage ; Glycosaminoglycans ; Hemostasis, Endoscopic ; Herpes Simplex ; Humans ; Immunocompromised Host ; Kidney ; Male ; Melena ; Methylmethacrylates ; Polystyrenes ; Simplexvirus ; Ulcer

Coinfection with herpes simplex virus and cytomegalovirus is a very rare cause of esophageal ulcer and upper gastrointestinal hemorrhage. A 26 year-old male kidney transplant recipient was referred with a complaint of melena. Upper gastrointestinal endoscopy showed a huge esophageal ulcer in the anastomosis site of the esophagogastrostomy. The ulcer occupied about two-thirds of the circumference of the esophageal lumen and an exposed vessel in the ulcer base was noted. Pathologic findings with immunohistochemical stain showed co-infection of herpes simplex virus and cytomegalovirus. He was treated successfully with endoscopic hemostasis and antiviral therapy. We report a case of upper gastrointestinal hemorrhage from esophageal ulcer caused by coinfection of herpes simplex virus and cytomegalovirus.
Coinfection ; Cytomegalovirus ; Endoscopy, Gastrointestinal ; Gastrointestinal Hemorrhage ; Glycosaminoglycans ; Hemostasis, Endoscopic ; Herpes Simplex ; Humans ; Immunocompromised Host ; Kidney ; Male ; Melena ; Methylmethacrylates ; Polystyrenes ; Simplexvirus ; Ulcer

BACKGROUND/AIMS: This study assessed the antibiotic resistance organisms isolated from the blood and bile of acute cholangitis and evaluated risk factors associated with them and their impact on clinical outcomes. METHODS: The identities and antibiotic resistance profiles of bacteria isolated from 433 cases of acute cholangitis from 346 patients were analyzed. Risk factors and the outcomes of patients infected with them were assessed. RESULTS: Microorganisms were isolated from 266 of 419 blood cultures and 256 of 260 bile cultures. Isolates from bile and blood were identical in 71% of the cases. A total of 20 extended spectrum-beta-lactamase (ESBL)-producers and 4 carbapenemase-producing organisms were isolated from blood, and 34 ESBL-producers and 13 carbapenemase-producers were isolated from bile. Sixty-four (14.8%) cases were infected with any one of these bacteria isolated from blood or bile. Risk factors associated with them in blood were nosocomial infection and prior biliary intervention. In bile, indwelling biliary device was a risk factor associated with them. Antibiotic-resistant bacteria were associated with mortality, independent of other prognostic factors. CONCLUSIONS: ESBL or carbapenemase-producing bacteria were frequently isolated in acute cholangitis patients especially with prior biliary intervention and nosocomial infection. Isolation of antibiotic-resistant bacteria was an independent risk factor of mortality.
Bacteria ; Bacterial Proteins ; beta-Lactamases ; Bile ; Cholangitis ; Cross Infection ; Drug Resistance, Microbial ; Humans ; Risk Factors

The publisher wishes to apologize for incorrectly displaying the author (Jung-Ho Han) name. We correct his name from Jung-Ho Han to Joung-Ho Han.