Effect of Combination Therapy with Sodium Ozagrel and Panax Ginseng on Transient Cerebral Ischemia Model in Rats

Sodium ozagrel (SO) prevents platelet aggregation and vasoconstriction in the cerebral ischemia. It plays an important role in the prevention of brain damage induced by cerebral ischemia/reperfusion. Recently, many animal studies have suggested that the Panax ginseng (PG) has neuroprotective effects in the ischemic brain. In this study, we assessed the neuroprotective effects that come from a combination therapy of SO and PG in rat models with middle cerebral artery occlusion (MCAO). Animals with MCAO were assigned randomly to one of the following four groups: (1) control (Con) group, (2) SO group (3 mg/kg, intravenously), (3) PG group (200 mg/kg, oral feeding), and (4) SO + PG group. The rats were subjected to a neurobehavior test including adhesive removal test and rotarod test at 1, 3, 7, 10, and 15 days after MCAO. The cerebral ischemic volume was quantified by Metamorph imaging software after 2-3-5-triphenyltetrazolium (TTC) staining. The neuronal cell survival and astrocytes expansion were assessed by immunohistofluorescence staining. In the adhesive removal test, the rats of PG or SO + PG group showed significantly better performance than those of the control group (Con: 88.1 ± 24.8, PG: 43.6 ± 11, SO + PG: 11.8 ± 7, P < .05). Notably, the combination therapy group (SO + PG) showed better performance than the SO group alone (SO: 56 ± 12, SO + PG: 11.8 ± 7, P < .05). In TTC staining for infarct volume, cerebral ischemic areas were also significantly reduced in the PG group and SO + PG group (Con: 219 ± 32, PG: 117 ± 8, SO + PG: 99 ± 11, P < .05). Immunohistofluorescence staining results showed that the group which received SO + PG group therapy had neuron cells in the normal range. They also had a low number of astrocytes and apoptotic cells compared with the control or SO group in the peri-infarction area. During astrocytes staining, compared to the SO + PG group, the PG group showed only minor differences in the number of NeuN-positive cells and quantitative analysis of infarct volume. In conclusion, these studies showed that in MCAO rat models, the combination therapy with SO and PG may provide better neuroprotective effects such as higher neuronal cell survival and inhibition of astrocytes expansion than monotherapy with SO alone

Motor-Evoked Potential Confirmation of Functional Improvement by Transplanted Bone Marrow Mesenchymal Stem Cell in the Ischemic Rat Brain

This study investigated the effect of bone marrow mesenchymal stem cells (BMSCs) on the motor pathway in the transient ischemic rat brain that were transplanted through the carotid artery, measuring motor-evoked potential (MEP) in the four limbs muscle and the atlantooccipital membrane, which was elicited after monopolar and bipolar transcortical stimulation. After monopolar stimulation, the latency of MEP was significantly prolonged, and the amplitude was less reduced in the BMSC group in comparison with the control group (P < .05). MEPs induced by bipolar stimulation in the left forelimb could be measured in 40% of the BMSC group and the I wave that was not detected in the control group was also detected in 40% of the BMSC group. Our preliminary results imply that BMSCs transplanted to the ischemic rat brain mediate effects on the functional recovery of the cerebral motor cortex and the motor pathway

A Pilot Study for the Neuroprotective Effect of Gongjin-dan on Transient Middle Cerebral Artery Occlusion-Induced Ischemic Rat Brain

In this study, we investigated whether gongjin-dan improves functional recovery and has neuroprotective effects on reducing the infarct volume after transient middle cerebral artery occlusion (MCAo). Infarct volume was measured using TTC staining and glucose utilization by F-18 FDG PET. Functional improvement was evaluated with the Rota-rod, treadmill, Garcia score test, and adhesive removal test. At 14 days after MCAo, neuronal cell survival, astrocytes expansion, and apoptosis were assessed by immunohistofluorescence staining in the peri-infarct region. Also, the expression of neurotrophic factors and inflammatory cytokines such as VEGF, BDNF, Cox-2, TNF-α, IL-1β, and IL-1α was measured in ischemic hemisphere regions. The gongjin-dan-treated group showed both reduced infarct volume and increased glucose utilization. Behavior tests demonstrated a significant improvement compared to the control. Also in the gongjin-dan treated group, NeuN-positive cells were increased and number of astrocytes, microglia, and apoptotic cells was significantly decreased compared with the control group in the ischemic peri-infarct area. Furthermore, the expression of VEGF and BDNF was increased and level of Cox-2, TNF-α, IL-1β, and IL-1α was decreased. These results suggest that gongjin-dan may improve functional outcome through the rapid restoration of metabolism and can be considered as a potential neuroprotective agent

Pharmacokinetic Estimation Models-based Approach to Predict Clinical Implications for CYP Induction by Calcitriol in Human Cryopreserved Hepatocytes and HepaRG Cells

Calcitriol, a vitamin D3 metabolite, is approved for various indications because it is the bioactive form of vitamin D in the body. The purpose of this study was to predict the clinical significance of cytochrome P450 (CYP) induction by calcitriol using in vitro human cryopreserved hepatocytes, HepaRG experimental systems, and various pharmacokinetic estimation models. CYP2B6, 3A4, 2C8, and 2C9 mRNA levels increased in a concentration-dependent manner in the presence of calcitriol in human cryopreserved hepatocytes and HepaRG cells. Using the half maximal effective concentration (EC50) and maximum induction effect (Emax) obtained from the in vitro study, a basic kinetic model was applied, suggesting clinical relevance. In addition, a static mechanistic model showed the improbability of a clinically significant effect; however, the calculated area under the plasma concentration–time curve ratio (AUCR) was marginal for CYP3A4 in HepaRG cells. To clarify the effect of CYP3A4 in vivo, physiologically based pharmacokinetic (PBPK) modeling was applied as a dynamic mechanistic model, revealing a low clinically significant effect of CYP3A4 induction by calcitriol. Therefore, we conclude that CYP induction by calcitriol treatment would not be clinically significant under typical clinical conditions

Long-Term Warming Trends in Korea and Contribution of Urbanization: An Updated Assessment

This study conducted an updated analysis of the long-term temperature trends over South Korea and reassessed the contribution of the urbanization effect to the local warming trends. Linear trends were analyzed for three different periods over South Korea in order to consider possible inhomogeneity due to changes in the number of available stations: recent 103 years (1912–2014), 61 years (1954–2014), and 42 years (1973–2014). The local temperature has increased by 1.90°C, 1.35°C, and 0.99°C during the three periods, respectively, which are found 1.4–2.6 times larger than the global land mean trends. The countries located in the northern middle and high latitudes exhibit similar warming trends (about 1.5 times stronger than the global mean), suggesting a weak influence of urbanization on the local warming over South Korea. Urbanization contribution is assessed using two methods. First, results from “city minus rural” methods showed that 30–45% of the local warming trends during recent four decades are likely due to the urbanization effect, depending on station classification methods and analysis periods. Results from an “observation minus reanalysis” method using the Twentieth Century Reanalysis (20CR) data sets (v2 and v2c) indicated about 25–30% contribution of the urbanization effect to the local warming trend during the recent six decades. However, the urbanization contribution was estimated as low as 3–11% when considering the century-long period. Our results confirm large uncertainties in the estimation of urbanization contribution when using shorter-term periods and suggest that the urbanization contribution to the century-long warming trends could be much lower.112sciescopu

Effect of an extract of Pinus koraiensis leaves, Lycium chinense fruit, and Saururus chinensis (Lour.) Baill. leaves on liver function in excessive drinkers: A randomized, double-blind, placebo-controlled trial

Chronic alcohol consumption is a major risk factor for alcoholic liver disease. In this study, we examined the effect of an extract of Pinus koraiensis leaves, Lycium chinense fruit, and Saururus chinensis (Lour.) Baill. leaves (PLC) on liver function in Korean. A randomized, double-blind, placebo-controlled study was performed in 50 excessive drinkers. The subjects were randomly assigned to PLC (n = 25, 2,000 mg/day) or placebo (n = 25) groups. Blood liver enzymes, lipid profiles, and antioxidant enzymes were assessed at baseline and 12 weeks. GGT level significantly decreased in women in the test group compared with the placebo group (-2.50 ± 3.54 U/L vs. 3.80 ± 11.23 U/L, P = 0.006). TC (-13.04 ± 25.65 mg/dL, P = 0.020) and LDL-C (-10.33 ± 24.15 mg/dL, P = 0.047) levels reduced in the test group after 12 weeks. Although PLC, appears the possibility of improving liver function in excessive drinkers, however, a larger scale and long-term intervention study should be performed

Has Global Warming Contributed to the Largest Number of Typhoons Affecting South Korea in September 2019?

A multimodel analysis indicates that the 2019 September record high number of typhoons affecting South Korea was contributed to mostly by the very strong convection over northwestern India with no discernible anthropogenic contribution. ?2021 American Meteorological Society11Nsciescopu

Crohn's disease and smoldering multiple myeloma: a case report and literature review

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) that presents with abdominal pain, weight loss, and diarrhea. Although the etiology has not been fully elucidated, both environmental and genetic causes are known to be involved. In chronic inflammatory conditions such as IBD, B lymphocytes are chronically stimulated, and they induce monoclonal expansion of plasma cells, sometimes resulting in monoclonal gammopathy of undetermined significance. Immunomodulators that are commonly used to control inflammation, such as tumor necrosis factor-α (TNF-α) blockers could increase the possibility of hematologic malignancy. The pathogenesis of multiple myeloma in association with TNF-α inhibitor therapy is attributed to decreased apoptosis of plasma cell populations. Here, we describe a case of a 36-year-old male patient who was diagnosed with immunoglobulin A subtype smoldering multiple myeloma during the treatment for CD with infliximab and adalimumab. We report this case along with a review of the literature on cases of multiple myeloma that occurred in conjunction with CD