Free radicals are known as an important factor which may act on reperfusion injury after transient or permanent brain ischemia. Numerous studies about cytotoxic function of free radical have been done. Most of these studies demonstrate the function of free radical in reperfusion injury by using radical scavenger or antioxidant as inhibitor of radicals. We used a modification of Karnovsky's Mn2 /diaminobenzidine (DAB) technique to demonstrate intravascular free radicals following transient occlusion and reperfusion of one middle cerebral artery in Sprague-Dawley rats. The MCA was occluded for 2 hours using an intraluminal suture method. The reperfusion time after transient ischemia was 1 hour, 6 hours, and 24 hours, respectively. Animals were perfused transcardially with solution containing Mn2 and DAB. After DAB perfusion, the brains were removed promptly, sectioned in frozen, and stained with methylene blue for light microscopic examination. Upon light microscopic examination, free radicals were confined within intravascular lumen and the amount of deposits increased according to the duration of reperfusion. Upon electron microscopic examination, free radicals were located in nuclear membrane and membrane of mitochondria and RER, and demonstrated as electron dense deposits. In addition, cell processes of the neuron revealed an electron dense deposits beneath the inner side of the membrane. In conclusion, free radicals demonstrated in the reperfusion injury area indicate that free radical acts as an important cytotoxic factor. Intracellular localization of free radicals may explain the relationship between free radical and delayed neuronal injury.
Animals ; Brain Ischemia* ; Brain* ; Free Radicals* ; Ischemia ; Membranes ; Methylene Blue ; Middle Cerebral Artery ; Mitochondria ; Neurons ; Nuclear Envelope ; Perfusion ; Rats, Sprague-Dawley ; Reperfusion Injury* ; Reperfusion* ; Sutures

Glycopeptides of the clinically important antibiotic drugs are glycosylated cyclic or polycyclic nonribosomal peptides. Glycopeptides such as vancomycin and teicoplanin are often used for the treatment of gram-positive bacteria in patients. The increased incidence of drug resistance and inadequacy of these therapeutics against gram-positive bacterial infections would be the formation and clinical development of more variable second generation of glycopeptide antibiotics: semisynthetic lipoglycopeptide analogs such as telavancin, dalbavancin, and oritavancin with improved activity and better pharmacokinetic properties. In this review, we describe the development of and bacterial resistance to vancomycin, teicoplanin, and semisynthetic glycopeptides (teicoplanin, dalbavancin, and oritavancin). The clinical influence of resistance to glycopeptides, particularly vancomycin, are also discussed.
Anti-Bacterial Agents* ; Drug Resistance ; Glycopeptides ; Gram-Positive Bacteria ; Gram-Positive Bacterial Infections ; Humans ; Incidence ; Peptides ; Teicoplanin ; Vancomycin

Resistance to antibiotics is becoming a very serious problem, with so-called superbugs exhibiting resistance to nearly all conventional antibiotic drugs. Consequently, these organisms often cause severe illness and even death. Alternatives to conventional antibiotics are antimicrobial peptides (AMPs). These widely expressed short peptides, which have been isolated from insects, plants, marine organisms and mammals, including humans, show strong antimicrobial activity against both Gram-negative and Gram-positive bacteria. Most AMPs act by disrupting the bacterial membrane through "Barrel-stave", "Toroidal pore", "carpet" mechanism. In addition, AMPs may prevent septic shock through strongly binding lipopolysaccharides and lipoteichoic acid located on the bacterial membrane. The action mechanisms of AMP to minimize the likelihood developing resistance to the peptides would be particular advantage. For these reasons, we anticipate that AMPs will replace conventional antibiotic drugs in a variety of contexts.
Anti-Bacterial Agents ; Aquatic Organisms ; Gram-Positive Bacteria ; Humans ; Insects ; Lipopolysaccharides ; Mammals ; Membranes* ; Peptides* ; Shock, Septic

BACKGROUND: Inducible nitric oxide synthase (iNOS) has been detected in a number of pathologic conditions in the central nervous system. This study was investigated the patterns of iNOS expression in the neuronal PC12 cell and the effects of nitric oxide on the apoptosis of PC12 cells. METHODS: The stimulating agents for induction of iNOS expression in PC12 cells were bacterial lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-), and interferon-gamma (IFN-). RESULTS: The expression iNOS mRNA and protein in PC12 cells stimulated with LPS/TNF-/IFN- were profoundly increased. The expression of iNOS mRNA arose at 6 hours, peaked at 12 hours, and declined to 48 hours after LPS/TNF-/ IFN- treatment. iNOS protein was increased up to 24 hours in LPS/TNF-/IFN- treated PC12 cells while the expression of nNOS was unaffected. Accumulation of NO derivatives in the culture media was markedly increased at least at up to 48 hours after LPS/TNF-/IFN- treatment. The induction of iNOS expression and NO production in differentiated PC12 cells was correlated with apoptotic cell death judged by transmission electron microscopy and DNA fragmentation from the results of the Terminal deoxynucleotidyl-transferase-mediated dUDP biotin nick end-labeling (TUNEL) method. After treatment with NOS inhibitor, N-monomethylarginine (NMMA), a profound decrease in NO production by LPS/TNF-/IFN- treated PC12 cells was noted. And the LPS/TNF-/IFN- induced apoptosis was prevented by the NMMA treatment. CONCLUSIONS: From the above results it is concluded that the expression of iNOS in differentiated PC12 cells is induced by the combined application of LPS, TNF-, and IFN-. And the apoptosis of cultured PC12 cells is mediated by iNOS-derived NO.
Animals ; Apoptosis* ; Biotin ; Cell Death ; Central Nervous System ; Culture Media ; DNA Fragmentation ; Interferon-gamma ; Microscopy, Electron, Transmission ; Necrosis* ; Neurons* ; Nitric Oxide Synthase Type II* ; Nitric Oxide* ; PC12 Cells* ; RNA, Messenger ; Tumor Necrosis Factor-alpha

Purpose: Repeated transcranial direct current stimulation (tDCS) is expected to have the potential to improve cognitive function in patients with mild cognitive impairment (MCI). We aimed to evaluate the efficacy and safety of at-home tDCS for elderly patients with MCI. Materials and Methods: Patients aged 60–80 years, who maintained normal daily living but reported objective memory impairments, were enrolled. Active or sham stimulations were applied to the dorsal frontal cortex (left: anode; right: cathode) at home for 2 weeks. Changes in cognitive function were assessed using visual recognition tasks and the Mini-Mental State Exam (MMSE), and safety and efficacy were assessed using self-reports and a remote monitoring application. Results: Of the 19 participants enrolled, 12 participants were included in the efficacy analysis. Response times and MMSE scores significantly improved after active stimulation compared to the sham stimulation; however, there were no significant differences in the proportion of correct responses. The mean compliance of the efficacy group was 97.5%±4.1%. Three participants experienced burns, but no permanent sequelae remained. Conclusion This preliminary result suggests that home-based tDCS may be a promising treatment option for MCI patients; however, it requires more attention and technological development to address safety concerns.

Objective: We aimed to investigate the associations of the triglyceride-glucose index, which measures insulin resistance, and the incidence of Parkinson’s disease. Methods: Our study used the Health Screening Cohort database of the National Health Insurance Service of South Korea (2002–2019). We included 310,021 participants who had no previous history of Parkinson’s disease and for whom more than 3 triglyceride-glucose index measurements were available. A diagnosis of Parkinson’s disease was determined via the International Classification of Diseases Tenth edition (G20) with a specific reimbursement code for rare intractable diseases and a history of prescriptions for anti-Parkinsonism drugs. Results: During a median of 9.64 years (interquartile range 8.72–10.53), 4,587 individuals (1.5%) had Parkinson’s disease. Based on a multivariable time-dependent Cox proportional hazards model, a per-unit increase in triglyceride-glucose index score was associated with a significantly increased risk of Parkinson’s disease (hazard ratio [HR]: 1.062; 95% confidence interval [CI] 1.007–1.119). In a sensitivity analysis, the triglyceride-glucose index was associated with the incidence of Parkinson’s disease in a non–diabetes mellitus cohort (HR: 1.093; 95% CI 1.025–1.165), but not in the diabetes mellitus cohort (HR: 0.990; 95% CI 0.902–1.087). In a restricted cubic spline analysis, the association between the triglyceride-glucose index and the incidence risk of Parkinson’s disease showed a nonlinear increasing (J-shaped) trend. Conclusion Our study demonstrated that higher triglyceride-glucose index scores were associated with the incidence of Parkinson’s disease in the general population, particularly in a nondiabetic mellitus cohort.

Objective: We aimed to investigate the associations of the triglyceride-glucose index, which measures insulin resistance, and the incidence of Parkinson’s disease. Methods: Our study used the Health Screening Cohort database of the National Health Insurance Service of South Korea (2002–2019). We included 310,021 participants who had no previous history of Parkinson’s disease and for whom more than 3 triglyceride-glucose index measurements were available. A diagnosis of Parkinson’s disease was determined via the International Classification of Diseases Tenth edition (G20) with a specific reimbursement code for rare intractable diseases and a history of prescriptions for anti-Parkinsonism drugs. Results: During a median of 9.64 years (interquartile range 8.72–10.53), 4,587 individuals (1.5%) had Parkinson’s disease. Based on a multivariable time-dependent Cox proportional hazards model, a per-unit increase in triglyceride-glucose index score was associated with a significantly increased risk of Parkinson’s disease (hazard ratio [HR]: 1.062; 95% confidence interval [CI] 1.007–1.119). In a sensitivity analysis, the triglyceride-glucose index was associated with the incidence of Parkinson’s disease in a non–diabetes mellitus cohort (HR: 1.093; 95% CI 1.025–1.165), but not in the diabetes mellitus cohort (HR: 0.990; 95% CI 0.902–1.087). In a restricted cubic spline analysis, the association between the triglyceride-glucose index and the incidence risk of Parkinson’s disease showed a nonlinear increasing (J-shaped) trend. Conclusion Our study demonstrated that higher triglyceride-glucose index scores were associated with the incidence of Parkinson’s disease in the general population, particularly in a nondiabetic mellitus cohort.

Objective: We aimed to investigate the associations of the triglyceride-glucose index, which measures insulin resistance, and the incidence of Parkinson’s disease. Methods: Our study used the Health Screening Cohort database of the National Health Insurance Service of South Korea (2002–2019). We included 310,021 participants who had no previous history of Parkinson’s disease and for whom more than 3 triglyceride-glucose index measurements were available. A diagnosis of Parkinson’s disease was determined via the International Classification of Diseases Tenth edition (G20) with a specific reimbursement code for rare intractable diseases and a history of prescriptions for anti-Parkinsonism drugs. Results: During a median of 9.64 years (interquartile range 8.72–10.53), 4,587 individuals (1.5%) had Parkinson’s disease. Based on a multivariable time-dependent Cox proportional hazards model, a per-unit increase in triglyceride-glucose index score was associated with a significantly increased risk of Parkinson’s disease (hazard ratio [HR]: 1.062; 95% confidence interval [CI] 1.007–1.119). In a sensitivity analysis, the triglyceride-glucose index was associated with the incidence of Parkinson’s disease in a non–diabetes mellitus cohort (HR: 1.093; 95% CI 1.025–1.165), but not in the diabetes mellitus cohort (HR: 0.990; 95% CI 0.902–1.087). In a restricted cubic spline analysis, the association between the triglyceride-glucose index and the incidence risk of Parkinson’s disease showed a nonlinear increasing (J-shaped) trend. Conclusion Our study demonstrated that higher triglyceride-glucose index scores were associated with the incidence of Parkinson’s disease in the general population, particularly in a nondiabetic mellitus cohort.

No abstract available.
Glycogen Storage Disease Type V* ; Glycogen Storage Disease* ; Glycogen* ; Humans ; Rhabdomyolysis* ; Seizures*

Purpose: We investigated the factors that affect the occurrence of sinusoidal obstruction syndrome (SOS) and the effect of SOS on the patient’s perioperative outcomes through histological review of liver resection specimens from patients who underwent chemotherapy. Methods: From December 2007 to December 2020, liver specimens from patients who underwent liver resection for colorectal liver metastasis after neoadjuvant chemotherapy were analyzed regarding liver damage in the nontumorous lesion. Through pathological review, patients with grade 1–3 sinusoidal dilatation were categorized into the SOS (+) group, compared to a control group (grade 0, SOS [–]). Results: Of 286 patients, 175 were included. Preoperative factors were similar between the groups. Although not statistically significant, the SOS (+) group had a shorter chemotherapy-free interval before resection (7.96 weeks vs. 10.0 weeks, P = 0.069). The SOS (+) group had higher intraoperative blood loss (889.1 ± 1,126.6 mL vs. 555.3 ± 566.7 mL, P = 0.012) and transfusion rates (46.6% vs. 25.3%, P = 0.003). SOS correlated with increased liver surgery-specific complications (40.9% vs. 26.4, P = 0.043). Patients with SOS experienced adverse effects on intrahepatic recurrent-free survival and overall survival (5-year survival, 46.0% vs. 33.9%; P = 0.014). Conclusion SOS development during liver surgery is associated with increased intraoperative blood loss, transfusion volume, and liver surgery-specific complications and has a higher risk of early recurrence and decreased overall survival.Thus, it is crucial to exercise caution during liver surgery in these patients.