Moon, Eunjung;Lee, Sung Ok;Kang, Tong Ho;Kim, Hye Ju;Choi, Sang Zin;Son, Mi-Won;Kim, Sun Yeou
Biomolecules & Therapeutics
/
v.22
no.5
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pp.445-452
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2014
The purpose of this study was to investigate the therapeutic effects of DA-9801, an optimized extract of Dioscorea species, on diabetic peripheral neuropathy in a type 2 diabetic animal model. In this study, db/db mice were treated with DA-9801 (30 and 100 mg/kg, daily, p.o.) for 12 weeks. DA-9801 reduced the blood glucose levels and increased the withdrawal latencies in hot plate tests. Moreover, it prevented nerve damage based on increased nerve conduction velocity and ultrastructural changes. Decrease of nerve growth factor (NGF) may have a detrimental effect on diabetic neuropathy. We previously reported NGF regulatory properties of the Dioscorea genus. In this study, DA-9801 induced NGF production in rat primary astrocytes. In addition, it increased NGF levels in the sciatic nerve and the plasma of type 2 diabetic animals. DA-9801 also increased neurite outgrowth and mRNA expression of Tieg1/Klf10, an NGF target gene, in PC12 cells. These results demonstrated the attenuation of diabetic peripheral neuropathy by oral treatment with DA-9801 via NGF regulation. DA-9801 is currently being evaluated in a phase II clinical study.
Purpose: Peripheral artery disease (PAD) is a form of arteriosclerosis that occurs in the extremities and involves ischemia. Previous studies have reported that patients with periodontitis are at high risk for PAD. However, the relationship between these 2 diseases has not yet been fully elucidated. In this cross-sectional study, we investigated this relationship by comparing patients with PAD to those with arrhythmia (ARR) as a control group. Methods: A large-scale survey was conducted of patients with cardiovascular disease who visited Tokyo Medical and Dental University Hospital. We investigated their oral condition and dental clinical measurements, including probing pocket depth, bleeding on probing, clinical attachment level, and number of missing teeth; we also collected salivary and subgingival plaque samples and peripheral blood samples. All patients with PAD were extracted from the whole population (n=25), and a matching number of patients with ARR were extracted (n=25). Simultaneously, ARR patients were matched to PAD patients in terms of age, gender, prevalence of diabetes, hypertension, dyslipidemia, obesity, and the smoking rate (n=25 in both groups). Real-time polymerase chain reaction was performed to measure the bacterial counts, while the enzyme-linked immunosorbent assay method was used to measure anti-bacterial antibody titers and proinflammatory cytokine levels in serum. Results: PAD patients had more missing teeth ($18.4{\pm}2.0$) and higher serum levels of C-reactive protein ($1.57{\pm}0.85mg/dL$) and tumor necrosis factor-alpha ($70.3{\pm}5.7pg/mL$) than ARR patients ($12.0{\pm}1.7$, $0.38{\pm}0.21mg/dL$, and $39.3{\pm}4.5pg/mL$, respectively). Meanwhile, no statistically significant differences were found in other dental clinical measurements, bacterial antibody titers, or bacterial counts between the 2 groups. Conclusions: Our findings suggested that PAD patients had poorer oral and periodontal state with enhanced systemic inflammation.
Background: It had been reported by authors that linear polarized infrared light radiation (Superizer: SL) near the stellate ganglion had a similar effect on the change of skin temperature of hand compared with the stellate ganglion block (SGB). We hypothesized that this was due to dilatation of vessels and an increased blood flow. The aim of this study was to measure the velocity of blood flow in peripheral vessels after linear polarized infrared light radiation near the stellate ganglion and to compare the effect of SL with that of SGB using local anesthetics. Methods: Forty patients whose clinical criteria were matched for the symptoms of SGB were selected for study. We radiated the stellate ganglion by linear polarized infrared light radiation and measured the blood flow of radial artery using Ultrasound Doppler blood flow meter before and after 10, 20 and 30 minutes post-radiation. After 3 days, SGB was performed using 8 ml of 1% mepivacaine to the same patient, and the radial artery blood flow was measured in the same manner. Results: The blood flow velocity was increased by 40% and 27% at 10 min and 20 min after SL and by 42% and 41% at 10 min and 20 min after SGB. However, there was no statistically significant difference in blood flow velocity between SGL and SGB. Conclusions: We could conclude that linear polarized radiation is a clinically simple and useful noninvasive therapeutic tool in clinical area.
Background: T cell mediated immunity is important in the defense mechanism of tuberculosis. Since ${\gamma}{\delta}$ T cell receptor was found to react with 65 kD heat shock protein of M.tuberculosis, there have been some reports on the role of ${\gamma}{\delta}$ T cells in the defense against M.tuberculosis. But until now, the role of the ${\gamma}{\delta}$ T cells in tuberculosis is not clear. Methods: We therefore measured the percentage of ${\gamma}{\delta}$ T cells of peripheral blood by flowcytometry before and after stimulation with Con-A, PPD and H37Ra lysate and compared between tuberculosis patients and healthy controls. Results: ${\gamma}{\delta}$ T cells of pheripheral blood in pulmonary tuberculosis patients was $7.5{\pm}5.2%$, showing no difference compared with healthy control($10.0{\pm}4.8%$). But IL-2R(+) ${\gamma}{\delta}$ T cells were higher in tuberculosis compared with healthy control($4.8{\pm}5.1%$ vs. $1.8{\pm}2.8%$). After stimulation with PPD or Con-A, the percentage of ${\gamma}{\delta}$ T cells showed no significant change, but IL-2R(+) ${\gamma}{\delta}$ T cells increased significantly in both tuberculosis($17.9{\pm}13.4%,\;57.6{\pm}20.2%$ respectively) and healthy control group($11.5{\pm}9.1%,\;80.8{\pm}9.3%$). After stimulation with H37Ra lysate, percentage of ${\gamma}{\delta}$ T cells showed increasing tendency in healthy control group, but it was not statistically significant. Conclusion: In this study, we could not demonstrate the role of ${\gamma}{\delta}$ T cells in the peripheral blood of pulmonary tuberculosis. It is suggested that further studies will be needed in the regional sites of M.tuberculosis infection.
Purpose : Hyper IgM syndrome(HIGM) is characterized by severe recurrent bacterial infections with decreased serum levels of IgG, IgA, and IgE but elevated IgM levels. Recently, it has been classified into three groups; HIGM1, HIGM2 and a rare form of HIGM. HIGM1 is a X-linked form of HIGM and has now been identified as a T-cell deficiency in which mutations occur in the gene that encodes the CD40 ligand molecule. HIGM2 is an autosomal recessive form of HIGM. Molecular studies have shown that the mutation of HIGM2 is in the gene that encodes activation-induced cytidine deaminase(AID). Recently, another rare form of X-linked HIGM syndrome associated with hypohydrotic ectodermal dysplasia has been identified. We encountered a patient with a varient form of HIGM2. To clarify the cause of this form of HIGM, we evaluated the peripheral B cells of this patient. Methods : The lymphocytes of the patient were prepared from peripheral blood. B cells were immortalized with the infection of EBV. Cell cycle analysis was done with the immortalized B cells of the patient. Peripheral mononuclear cells were stained with monoclonal anti-CD40L antibody. Total RNA was extracted from the peripheral mononuclear cells. After RT-PCR, direct sequencing for CD40L gene and HuAID gene were done. Immunostainings of a lymph node for CD3, CD23, CD40, Fas-L, bcl-2, BAX were done. Results : The peripheral B cells of this patient showed normal expression of CD40L molecule and normal sequencing of CD40L gene, and also normal sequencing of AID gene. Interestingly, the peripheral B cells of this patient showed a decreased population of G2/mitosis phase in cell cycles which recovered to normal with the stimulation of IL-4. Conclusion : We suspect that the cause of increased serum IgM in this patient may be from a decrease of G2/mitosis phase of the peripheral B cells, which may be from the decreased production or secretion of IL-4. Therefore, this may be a new form of HIGM.
For centuries, ginseng has been used for the therapeutic purpose in oriental herb medicine. Several studies have been conducted in the past to evaluate the effect of ginseng on erythropoiesis. However the results were controversial. We therefore attempted in the present studies to evaluate the effect of ginseng on the erythropoietic activity. In one series of experiments, the recovery pattern of peripheral blood(red cell count, hemoglobin content, hematocrit and reticulocyte count) was studied in posthemorrhagic anemic rabbits. After animals were maintained with normal(control group) or 1 gm% ginseng (experimental group) diet for 2 weeks, hemorrhagic anemia was induced by withdrawing blood equivalent to 25% of the total blood volume and then changes in peripheral blood were followed for following 30 days. In other series of experiments, we studied effect of ginseng on erythrokinetics using $^{59}Fe$. $^{59}Fe(10{\sim}40\;{\mu}Ci/animal)$ was injected intravenously after animals were fed with normal (control group) or 1 gm% ginseng(experimental group) diet for 2 weeks. And radioactivities in the blood compartments were measured at appropriate intervals for 15 days. Front these various erythrokinetic parameters were estimated. Results are summarized as follows: 1) Reticulocyte count was higher in the experimental group than in the control group after 2 weeks of administration of experimental diet. During the posthemorrhagic period, the reticulocyte count increased in both the control and experimental groups, but the increase appeared much earlier in the experimental group. 2) The posthemorrhagic recoveries of hematocrit, hemoglobin content and red cell count appeared to be faster in the experimental group as compaired with the control group. 3) The half life$(T_{1/2})$ of $^{59}Fe$ in the plasma was significantly(P<0.05) shorter in the experimental group(82.6 min, N=8) than in the control group(121 min, N=6). Plasma iron turnover (PIT) of the experimental group (1.78 mg/dl/24 hr.) was approximately 4 times greater than that of the control group(0.45 mg/dl/24 hr.). 4) The maximum red cell utilization(RC-U) was 82.1% in the experimental group ana 74.5% in the control group. Red cell iron turnover(RIT) of the experimental group(1.62 mg/dl/24 hr.) was slightly higher than that of the control group(0.35 mg/dl/24 hr). 5) Erythron turnover was significantly(p<0.05) greater in the experimental group(1.27 mg/dl/24 hr.) than in the control group(0.24 mg/dl/24 hr.). Marrow transit time of the experimental group(2.05 days) tended to he faster than that of the control group(2.84 days). These results suggest that the gingseng improves the recovery of posthemorrhagic anemia and stimulates the erythropoiesis in rabbits.
Purpose: This study compared outcomes in children with acute leukemia who underwent transplantations with umbilical cord blood (UCB), bone marrow, or peripheral blood stem cells from a human leukocyte antigen (HLA)-matched related donor (MRD) or an unrelated donor (URD). Methods: This retrospective study included consecutive acute leukemia patients who underwent their first allogeneic hematopoietic stem cell transplantation (HSCT) at Samsung Medical Center between 2005 and 2010. Patients received stem cells from MRD (n=33), URD (n=46), or UCB (n=41). Results: Neutrophil and platelet recovery were significantly longer after HSCT with UCB than with MRD or URD ($p$ <0.01 for both). In multivariate analysis using the MRD group as a reference, the URD group had a significantly higher risk of grade III to IV acute graft-versus-host disease (GVHD; relative risk [RR], 15.2; 95% confidence interval [CI], 1.2 to 186.2; $p$=0.03) and extensive chronic GVHD (RR, 6.9; 95% CI, 1.9 to 25.2; $p$ <0.01). For all 3 donor types, 5-year event-free survival (EFS) and overall survival were similar. Extensive chronic GVHD was associated with fewer relapses (RR, 0.1; 95% CI, 0.04 to 0.6; $p$ <0.01). Multivariate analysis showed that lower EFS was associated with advanced disease at transplantation (RR, 3.2; 95% CI, 1.3 to 7.8; $p$ <0.01) and total body irradiation (RR, 2.1; 95% CI, 1.0 to 4.3; $p$=0.04). Conclusion: Survival after UCB transplantation was similar to survival after MRD and URD transplantation. For patients lacking an HLA matched donor, the use of UCB is a suitable alternative.
Background: It is reported that the percentage of smudge cells in the blood smear could be a prognostic indicator in chronic lymphocytic leukemia. However, the clinical significance of smudge cells in other hematological malignancies, solid tumors or non-malignant diseases is less clear. Hence, this study was conducted to survey the clinical significance of smudge cells in hematological cancers and other disorders. Materials and Methods: From January to November, 2015, the clinical data of patients who received blood examination with differential counts for clinical purpose and were found to have smudge cells in the peripheral blood film in Far Eastern Memorial Hospital were selected. The percentage of smudge cells and patient outcomes were evaluated for further univariate and survival analyses. Results: A total of 102 patients with smudge cells in their blood smears were included. Smudge cells were frequently presented in out-of-hospital cardiac arrest (OHCA; n=30), infections (n=23), hematological cancers (n=23) and solid cancers (n=10). There was no relationship between the percentage of smudge cells and the patient mortality in all diseases (OR: 1.08, 95% CI: 0.47-2.48, P=1.000) as well as the OHCA group (OR: 1.91, 95% CI: 0.38-9.60, P=0.694). It was observed that in patients with all cancers with the percentage of smudge cells less than 50% had a lower mortality rate in comparison with those who had the percentage of smudge cells of 50% or more (OR: 22.29, 95% CI: 2.38-208.80, P<0.001). Additionally, it was seemingly that patients with smudge cells of 50% or more had a lower survival rate than those with smudge cells less than 50% in all cancers with follow-up at 2-month intervals, but without statistical significance (P=0.064). Conclusions: Our survey indicated that in all cancers, those who had higher percentage of smudge cells were prone to have poor outcomes when compared with the subjects with lower percentage of smudge cells. This finding was quite different from the results of previous studies in which the race-ethnicity of most study populations was non-Asian; hence, further investigations are required. Besides, there was no apparent association of the percentage of smudge cells with patient outcomes in all diseases, including OHCA.
Hypereosinophilic syndrome is a rare hematologic disorder with sustained eosinophilia. Peripheral blood eosinophilia without an underlying etiology and with organs dysfunction has been designated hypereosinophilic syndrome. We report a rare case of symptomatic spinal infiltration of eosinophils at osteolytic T5 in patient with idiopathic hypereosinophilic syndrome.
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