Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.

BACKGROUND: Numerous studies have suggested that polyunsaturated fatty acids (PUFAs)-supplemented diets may decrease cardiovascular morbidity and mortality. Especially, omega-3 PUFAs may exert beneficial effects to the treatment and prevention of dyslipidemias, arrhythmias, atherosclerosis, and hypertension. METHODS: This study investigated plasma lipid profiles including total cholesterol, triglycerides (TG), LDL, HDL, and antioxidant status indicative of vitamin A, vitamin E, malondialdehyde (MDA) and distribution of plasma long-chain fatty acids (C12-C24) in 28 normal subjects and 24 hypertensive patients. Also, the correlation among PUFAs, levels of antioxidant status, and lipid profiles of the subjects were estimated. RESULTS: The distribution of omega-3 PUFAs, saturated fatty acids, and monounsaturated fatty acids showed significant differences (P<0.05), but that of omega-6 PUFAs did not exhibit significant differences. The omega-6/omega-3 ratio exhibited 36.96 in normal group and 14.29 in the hypertensive patient group. The levels of vitamin A, vitamin E, and MDA were increased significantly in the hypertensive patient group. CONCLUSION: PUFA levels were estimated in the hypertensive patients and normal group. The results suggest that dietary intake of proper omega-6/omega-3 ratio is needed for prevention and treatment of hypertension.
Arrhythmias, Cardiac ; Atherosclerosis ; Cholesterol ; Diet ; Dyslipidemias ; Fatty Acids ; Fatty Acids, Monounsaturated ; Fatty Acids, Unsaturated ; Humans ; Hypertension ; Malondialdehyde ; Plasma ; Triglycerides ; Vitamin A ; Vitamin E ; Vitamins

OBJECTIVE: The purpose of the present study was to investigate the efficacy, safety, and tolerability of aripiprazole in patients with schizophrenia, schizophreniform disorder, and schizoaffective disorder during acute treatment phase. METHODS: Prospective, multicenter, single group, and 8-week study was conducted in patients with schizophrenia, schizophreniform disorder, and schizoaffective disorder. A total of 300 patients were enrolled in the present study. The primary efficacy measure was the Positive and Negative Syndrome Scale (PANSS) total score, and secondary efficacy measures were the PANSS positive and negative subscales scores, and Clinical Global Impression-Severity of Illness (CGI-S) score. Treatment-emergent adverse events, extrapyramidal symptoms (EPS), weight, vital signs, and laboratory tests were assessed as measures of tolerability and safety. RESULTS: Significant improvements in all efficacy measures were achieved by aripiprazole as early as 1-week and sustained through 8-week period. First-episode patients showed greater improvements in PANSS total, positive subscale score, and CGI-S score, compared with recurrent patients. Slightly increased akathisia (+0.32 from baseline score of Barnes Akathisia Rating Scale, p=0.033) and weight gain (1.15+/-3.44 kg, p<0.001) were observed by aripiprazole during 8-week acute treatment phase. CONCLUSION: The present study demonstrated that aripiprazole was effective in acute treatment of positive and negative symptoms of schizophrenia, schizophreniform disorder, and schizoaffective disorder. In general, aripiprazole showed favorable safety and tolerability profiles, although clinicians needed to pay attention to the possibility of akathisia and weight gain by aripiprazole in first-episode patients during acute treatment phase.
Humans ; Piperazines ; Prospective Studies ; Psychomotor Agitation ; Psychotic Disorders ; Quinolones ; Schizophrenia ; Vital Signs ; Weight Gain ; Aripiprazole

OBJECTIVE: The purpose of the present study was to investigate the efficacy, safety, and tolerability of aripiprazole in patients with schizophrenia, schizophreniform disorder, and schizoaffective disorder during acute treatment phase. METHODS: Prospective, multicenter, single group, and 8-week study was conducted in patients with schizophrenia, schizophreniform disorder, and schizoaffective disorder. A total of 300 patients were enrolled in the present study. The primary efficacy measure was the Positive and Negative Syndrome Scale (PANSS) total score, and secondary efficacy measures were the PANSS positive and negative subscales scores, and Clinical Global Impression-Severity of Illness (CGI-S) score. Treatment-emergent adverse events, extrapyramidal symptoms (EPS), weight, vital signs, and laboratory tests were assessed as measures of tolerability and safety. RESULTS: Significant improvements in all efficacy measures were achieved by aripiprazole as early as 1-week and sustained through 8-week period. First-episode patients showed greater improvements in PANSS total, positive subscale score, and CGI-S score, compared with recurrent patients. Slightly increased akathisia (+0.32 from baseline score of Barnes Akathisia Rating Scale, p=0.033) and weight gain (1.15+/-3.44 kg, p<0.001) were observed by aripiprazole during 8-week acute treatment phase. CONCLUSION: The present study demonstrated that aripiprazole was effective in acute treatment of positive and negative symptoms of schizophrenia, schizophreniform disorder, and schizoaffective disorder. In general, aripiprazole showed favorable safety and tolerability profiles, although clinicians needed to pay attention to the possibility of akathisia and weight gain by aripiprazole in first-episode patients during acute treatment phase.
Humans ; Piperazines ; Prospective Studies ; Psychomotor Agitation ; Psychotic Disorders ; Quinolones ; Schizophrenia ; Vital Signs ; Weight Gain ; Aripiprazole

Neuroprotective properties of lithium were evaluated by using in vivo NMDA excitotoxicity model. Systemic injection of NMDA to young mice induced neuronal apoptosis mediated by both TNFR-1 and Fas ligand, and long-term lithium treatment showed noticeable neuroprotection against NMDA-induced excitotoxicity: NMDA-damaged neurons expressed several apoptosis-related gene products such as TNFR-1, Fas ligand, and caspase-3, and these gene expressions were not found in the brain of mice chronically treated with lithium. Therefore, it is highly likely that the protection offered by chronic lithium treatment occurred at far upstream of caspase activation, since the chronic lithium treatment increased the expression of Bcl-2, an important antiapoptotic gene known to act upstream of caspase cascade. Timm's histochemistry indicated the complete blockade of the NMDA insults by the treatment. There was no indication of axonal regeneration, which follows synaptic degeneration induced by neuronal damage. Furthermore, this study reports for the first time that TNFR-1 and Fas ligand are involved in neuroprotective effects of lithium in NMDA-induced neuronal apoptosis.
Animals ; Apoptosis ; Axons ; Brain ; Caspase 3 ; Cerebrum* ; Fas Ligand Protein ; Gene Expression ; Lithium* ; Mice* ; N-Methylaspartate ; Neurons ; Neuroprotective Agents* ; Regeneration

BACKGROUND: The committee of tuberculosis(TB) survey planning for the year 2000 decided to construct the Korean Tuberculosis Surveillance System (KTBS), based on a doctor's routine reporting method. The successful keys of the KTBS rely on the precision of the recorded TB notification forms. The purpose of this study was to determine that the accuracy of the TB notification form written at a private general hospital given to the corresponding health center and to improve the comprehensiveness of these reporting systems. MATERIALS AND METHODS: 291 adult TB patients who had been diagnosed from August 2000 to January 2001, were enrolled in this study. The lists of TB notification forms were compared with the medical records and the various laboratory results; case characteristics, history of previous treatment, examinations for diagnosis, site of the TB by the international classification of the disease, and treatment. RESULTS: In the list of examinations for a diagnosis in 222 pulmonary TB patients, the concordance rate of the 'sputum smear exam' was 76% but that of the 'sputum culture exam' was only 23%. Among the 198 cases of the sputum culture exam labeled 'not examined', 43(21.7%) cases proved to be true 'not examined', 70 cases(35.4%) were proven to be 'culture positive', and 85(43.0%) cases were proven to be 'culture negative'. In the list of examinations for a diagnosis in 69 extrapulmonary TB patients, the concordance rate of the 'smear exam other than sputum' was 54%. In the list of treatments, the overall concordance rate of the 'type of registration' in the TB notification form was 85%. Among the 246 'new' cases on the TB notification form, 217(88%) cases were true 'new' cases and 13 were proven to be 'relapse', 2 were proven to be 'treatment after failure', one was proven to be 'treatment after default', 12 were proven to be 'transferred-in' and one was proven to be 'chronic'. Among the 204 HREZ prescribed regimen, 172(84.3%) patients were taking the HREZ regimen, and the others were prescribed other drug regimens. CONCLUSION: Correct recording of the TB notification form at the private sectors is necessary for supporting the effective TB surveillance system in Korea.
Adult ; Classification ; Diagnosis ; Hospitals, General* ; Humans ; Korea ; Medical Records ; Private Sector ; Sputum ; Tuberculosis*

Coptis chinensis (CC) is one of the traditional herbs used in Oriental medicine for the treatment of gastrointestinal disorders, anxiety, and insomnia. In this study, neurotrophic and neuritogenic effects of CC on rat pheochromocytoma (PC12) cells were evaluated. Pretreatment of PC12 cells with water extracts of CC (120microgram/ml) produced considerable outgrowth of neurites that is comparable to the effect of nerve growth factor (NGF). Therefore, neurite outgrowth was quantified and expression of NGF mRNA was examined. Furthermore, characteristics of neurites were immunocytochemically confirmed using axon and dendrite-specific antibodies. These results suggest that water extracts of CC contain components that have neurotrophic and neuritogenic properties.
Animals ; Antibodies ; Anxiety Disorders ; Axons ; Coptis* ; Medicine, East Asian Traditional ; Nerve Growth Factor ; Neurites ; PC12 Cells* ; Pheochromocytoma ; Rats ; RNA, Messenger ; Sleep Initiation and Maintenance Disorders ; Water*

BACKGROUND: Although cardiac hypertrophy contributes to cardiac failure, the underlying mechanism has not yet been precisely determined. This study was planned in order to determine the pathogenesis of heart failure following cardiac hypertrophy induced by -adrenergic stimulation. METHODS: The extent of cardiac hypertrophy was assessed after administrating isoproterenol (ISO, 5 mg/kg) intraperitoneally for 6 hours, 1, 3, 5, 7 and 10 days. The hematoxylin-eosin, Masson's trichrome and phosphotungstic acid hematoxylin stains along with immunohistochemical stainings for proliferating cell nuclear antigen and Ki-67 were performed in the paraffin-embedded left ventricle sections. Apoptosis was assessed by DNA laddering and terminal deoxynucleotidyl transferase TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay. TUNEL positive myocytes and some nonmyocytes appeared in the subepicardium at 6 hours after ISO administration. The localization of these cells was shifted to the subendocardium within 24 hours, and the TUNEL positive cells were seen throughout the myocardium on the 5th day after ISO treatment. Necrotic myocyte death occurred on the 3rd day of ISO administration in the subendocardium, and initial pericellular fibrosis was followed and increased thereafter, with replacement fibrosis accompanied by further necrotic myocyte cell death. CONCLUSIONS: Our data showed that ISO treatment induced apoptotic myocyte death and superimposed necrotic myocyte death with subsequent fibrosis. The observed cardiac myocyte death may reflect myocardial dysfunction.
Animals ; Apoptosis ; Cardiomegaly* ; Cell Death* ; Coloring Agents ; DNA ; DNA Nucleotidylexotransferase ; Fibrosis ; Heart Failure ; Heart Ventricles ; Hematoxylin ; Hypertrophy ; In Situ Nick-End Labeling ; Isoproterenol ; Muscle Cells ; Myocardium ; Myocytes, Cardiac* ; Phosphotungstic Acid ; Proliferating Cell Nuclear Antigen ; Rats*

The existence of opioid receptors in mammalian cerebellum except human, has not been clearly understood. In the present study, we found that NPY was inducible by morphine in the mouse cerebellar granular and Purkinje cell layers. We performed in situ RT-PCR and immunohistochemistry to characterize the NPY expression. The increase of NPY gene expression by morphine (30 mg/kg, i.p.) was inhibited by pretreatment with not only naloxone (100 mg/kg, i.p.) but also a noncompetitive NMDA antagonist, MK-801 (0.3 mg/kg, i.p.). The competitive NMDA antagonist, AP-5 (0.9 mg/kg, i.p.) slightly attenuated the increased NPY expression by morphine. Also, the finding similar to morphine was shown by NMDA (70 mg/kg, i.p.) treatment. Our results indicate that NPY was inducible by morphine and this might reflect activation of NMDA receptors in granule cells that relay mossy fiber inputs to Purkinje cells via parallel fibers.
Animals ; Cerebellum* ; Dizocilpine Maleate ; Gene Expression ; Humans ; Immunohistochemistry ; Mice* ; Morphine* ; N-Methylaspartate* ; Naloxone ; Negotiating* ; Neuropeptide Y* ; Neuropeptides* ; Purkinje Cells ; Receptors, N-Methyl-D-Aspartate ; Receptors, Opioid

Neuroprotective properties of lithium were investigated by using in vivo NMDA excitotoxicity model. The appearance of TUNEL positive cells was prominent within 24 h of NMDA (70 mg/kg, i.p.) injection in the regions of the cortex, hippocampal formation, and thalamus of mouse cerebrum. NMDA treatment resulted in the extensive enhancement of Bax immunoreactivity in the cortical and hippocampal regions. NMDA also increased the immunoreactivity of caspase 8 in the similar regions of the mouse cerebrum. However, the increased immunoreactivity of Bax and caspase 8 were dramatically attenuated by chronic lithium pretreatment (lithium chloride, 300 mg/kg/d, i.p. for 7-10 days). At the same time, lithium ion blocked the appearance of TUNEL positive cells, and the morphological assessment indicated an effective neuroprotection by lithium against NMDA excitotoxicity. Although the exact action mechanism of lithium is not straightforward at this time, we propose that the inhibition of Bax and caspase cascade is involved in the neuroprotective action of lithium.
Animals ; Caspase 8* ; Cerebrum ; Hippocampus ; In Situ Nick-End Labeling ; Lithium* ; Mice ; N-Methylaspartate ; Thalamus