Heart Rate Variability as an Early Objective Indicator of Subjective Feeling of Depression in Daily Life / 대한의료정보학회지

Objectives@#Changes in the autonomic nervous system have been observed in patients with depressive disorders by measuring their heart rate variability (HRV). However, whether HRV associates with depressive events in healthy people remains unknown. @*Methods@#Four healthy people participated in the present study. Their HRVs were measured routinely for 6 to 13 months. During this time, two participants reported experiencing two and three bouts of depression, respectively. This approach allowed us to examine changes in the participants’ HRVs by comparing their HRVs from before and after the unexpected depressive events. Changes in HRV were compared against those of two participants who did not report any depressive event. @*Results@#Participants’ low frequency/high frequency (LF/HF) ratios of HRV were lower after the event of depression than before. Their LF/HF ratios increased after recovery from the depressive events. In contrast, two participants who did not report any depressive event showed relatively smaller changes in their LF/HF ratios across measurements. @*Conclusions@#These results suggest that the LF/HF ratio may provide an objective measure of subjective experiences of depression and help identify potential cases of clinical depression.

Heart Rate Variability as an Early Objective Indicator of Subjective Feeling of Depression in Daily Life / 대한의료정보학회지

Objectives@#Changes in the autonomic nervous system have been observed in patients with depressive disorders by measuring their heart rate variability (HRV). However, whether HRV associates with depressive events in healthy people remains unknown. @*Methods@#Four healthy people participated in the present study. Their HRVs were measured routinely for 6 to 13 months. During this time, two participants reported experiencing two and three bouts of depression, respectively. This approach allowed us to examine changes in the participants’ HRVs by comparing their HRVs from before and after the unexpected depressive events. Changes in HRV were compared against those of two participants who did not report any depressive event. @*Results@#Participants’ low frequency/high frequency (LF/HF) ratios of HRV were lower after the event of depression than before. Their LF/HF ratios increased after recovery from the depressive events. In contrast, two participants who did not report any depressive event showed relatively smaller changes in their LF/HF ratios across measurements. @*Conclusions@#These results suggest that the LF/HF ratio may provide an objective measure of subjective experiences of depression and help identify potential cases of clinical depression.

Calpain-2 as a Treatment Target in Prenatal Stress-induced Epileptic Spasms in Infant Rats

Stress can induce a serious epileptic encephalopathy that occurs during early infancy. Recent studies have revealed that prenatal stress exposure is a risk factor for the development of infantile spasms. Our previous work demonstrates that prenatal stress with betamethasone-induced alterations to the expression of the K⁺/Cl⁻ co-transporter (KCC2) in gamma-aminobutyric acid (GABA) interneurons lowers the seizure threshold in exposed animals. Here, we further investigated the mechanisms involved in this KCC2 dysfunction and explored possible treatment options. We stressed Sprague-Dawley rats prenatally and further treated dams with betamethasone on gestational day 15, which increases seizure susceptibility and NMDA (N-Methyl-D-aspartate)-triggered spasms on postnatal day 15. In this animal model, first, we evaluated baseline calpain activity. Second, we examined the cleavage and dephosphorylation of KCC2. Finally, we checked the effect of a calpain inhibitor on seizure occurrence. The phosphorylated-N-methyl-D-aspartate Receptor 2B (NR2B):non-phosphorylated NR2B ratio was found to be higher in the cortex of the prenatally stressed beta-methasone model. We further found that the betamethasone model exhibited increased phosphorylation of calpain-2 and decreased phosphorylation of KCC2 and Glutamic acid decarboxylase 67 (GAD67). After using a calpain inhibitor in prenatal-stress rats, the seizure frequency decreased, while latency increased. GABAergic depolarization was further normalized in prenatal-stress rats treated with the calpain inhibitor. Our study suggests that calpain-dependent cleavage and dephosphorylation of KCC2 decreased the seizure threshold of rats under prenatal stress. Calpain-2 functions might, thus, be targeted in the future for the development of treatments for epileptic spasms.

Bone regeneration with umbilical cord blood mesenchymal stem cells in femoral defects of ovariectomized rats

OBJECTIVES: Current treatments for osteoporosis were prevention of progression, yet it has been questionable in the stimulation of bone growth. The mesenchymal stem cells (MSCs) treatment for osteoporosis aims to induce differentiation of bone progenitor cells into bone-forming osteoblasts. We investigate whether human umbilical cord blood (hUCB)-MSCs transplantation may induce bone regeneration for osteoporotic rat model induced by ovariectomy. METHODS: The ovariectomized (OVX) group (n = 10) and OVX-MSCs group (n = 10) underwent bilateral ovariectomy to induce osteoporosis, while the Sham group (n = 10) underwent sham operation at aged 12 weeks. After a femoral defect was made at 9 months, Sham group and OVX group were injected with Hartmann solution, while the OVX-MSCs group was injected with Hartmann solution containing 1 × 107 hUCB-MSCs. The volume of regenerated bone was evaluated using micro-computed tomography at 4 and 8 weeks postoperation. RESULTS: At 4- and 8-week postoperation, the OVX group (5.0% ± 1.5%; 6.1% ± 0.7%) had a significantly lower regenerated bone volume than the Sham group (8.6% ± 1.3%; 12.0% ± 1.8%, P < 0.01), respectively. However, there was no significant difference between the OVX-MSCs and Sham groups. The OVX-MSCs group resulted in about 53% and 65% significantly higher new bone formation than the OVX group (7.7% ± 1.9%; 10.0% ± 2.9%, P < 0.05). CONCLUSIONS: hUCB-MSCs in bone defects may enhance bone regeneration in osteoporotic rat model similar to nonosteoporotic bone regeneration. hUCB-MSCs may be a promising alternative stem cell therapy for osteoporosis.

Astrocytic Expression of CTMP Following an Excitotoxic Lesion in the Mouse Hippocampus

Akt (also known as protein kinase B, PKB) has been seen to play a role in astrocyte activation of neuroprotection; however, the underlying mechanism on deregulation of Akt signaling in brain injuries is not fully understood. We investigated the role of carboxy-terminal modulator protein (CTMP), an endogenous Akt inhibitor, in brain injury following kainic acid (KA)-induced neurodegeneration of mouse hippocampus. In control mice, there was a weak signal for CTMP in the hippocampus, but CTMP was markedly increased in the astrocytes 3 days after KA treatment. To further investigate the effectiveness of Akt signaling, the phosphorylation of CTMP was examined. KA treatment induced an increased p-CTMP expression in the astrocytes of hippocampus at 1 day. LPS/IFN-γ-treatment on primary astrocytes promoted the p-CTMP was followed by phosphorylation of Akt and finally upregulation of CTMP and p-CREB. Time-dependent expression of p-CTMP, p-Akt, p-CREB, and CTMP indicate that LPS/IFN-γ-induced phosphorylation of CTMP can activate Akt/CREB signaling, whereas lately emerging enhancement of CTMP can inhibit it. These results suggest that elevation of CTMP in the astrocytes may suppress Akt activity and ultimately negatively affect the outcome of astrocyte activation (astroglisiois). Early time point enhancers of phosphorylation of CTMP and/or late time inhibitors specifically targeting CTMP may be beneficial in astrocyte activation for neuroprotection within treatment in neuroinflammatory conditions.

Growth Differentiation Factor 15 Expression in Astrocytes After Excitotoxic Lesion in the Mouse Hippocampus

Growth differentiation factor 15 (GDF15) is, a member of the transforming growth factor beta (TGF-beta) superfamily of proteins. Although GDF15 is well established as a potent neurotrophic factor for neurons, little is known about its role in glial cells under neuropathological conditions. We monitored GDF15 expression in astrocyte activation after a kainic acid (KA)-induced neurodegeneration in the ICR mice hippocampus. In control, GDF15 immunoreactivity (IR) was evident in the neuronal layer of the hippocampus; however, GDF15 expression had increased in activated astrocytes throughout the hippocampal region at day 3 after the treatment with KA. LPS treatment in astrocytes dramatically increased GDF15 expression in primary astrocytes. In addition, LPS treatment resulted in the decrease of the IkappaB-alpha degradation and increase of the phosphorylation level of RelA/p65. These results indicate that GDF15 has a potential link to NF-kappaB activation, making GDF15 a valuable target for modulating inflammatory conditions.

A mild decrease of renal function is related to increased hemoglobin level during 5-year follow-up period

BACKGROUND/AIMS: We analyzed chronological changes in hemoglobin according to renal function changes over a 5-year follow-up period. METHODS: We enrolled 5,266 adults with a glomerular filtration rate (GFR) > or = 60 mL/min/1.73 m2 at an initial examination at a routine health check-up; a follow-up examination was conducted 5 years later. We categorized the subjects according to GFR ratio (groups 1, 2, and 3, defined as GFRratio > or = 1.00, 0.75 to 0.99, and or = 90 mL/min/1.73 m2 at the initial examination (all p or = 60 mL/min/1.73 m2, a mild decrease in GFR over a 5-year follow-up period was associated with an increase in hemoglobin levels.

Correlation between periodontitis and chronic kidney disease in Korean adults

BACKGROUND: Periodontitis and chronic kidney disease (CKD) are important health issues; however,the association between periodontitis and CKD markers, especially in Korean adults,remains elusive. METHODS: Data on 15,729 Korean adults were obtained from the Korean National Health and Nutritional Examination Surveys IV and V. The CKD markers included a decreased estimated glomerular filtration rate (eGFR;<60 mL/min/1.73m2), proteinuria, and hematuria. Odds ratios (ORs) and 95% confidence intervals were measured using stepwise multivariate logistic regression analyses for CKD markers based on the presence of periodontitis. RESULTS: Patients with periodontitis had greater unadjusted ORs for CKD markers compared to those without periodontitis, as follows: decreased eGFR,4.07(3.11-5.33); proteinuria, 2.12(1.48-3.05); and hematuria, 1.25 (1.13-1.39, all P<0.001). Periodontitis was a significant predictor of decreased eGFR independent of allcovariates [1.39 (1.03-1.89), P=0.034]. However, the effect of periodontitis on decreased eGFR seemed to be affected by hypertension and diabetes mellitus. Periodontitis was not an independent predictor of proteinuria; the significance disappeared after adjusting for hypertension and diabetes mellitus. Periodontitis was significantly correlated with hematuria, leading to similar ORs regardless of the adjustment for covariates[1.29 (1.15-1.46), P<0.001]. CONCLUSION: This study confirms the correlation between periodontitis and CKD markers, including decreased eGFR, proteinuria, and hematuria in Korean adults.

A Case of Chronic Renal Failure Associated with Systemic Capillary Leak Syndrome / 영남의대학술지

Systemic capillary leak syndrome (SCLS) is an unusual entity characterized by hypovolemic shock, hemoconcentration, and hypo-albuminemia associated with paraproteinemia as a result of marked capillary hyperpermeability. Complications of this syndrome can include compartment syndromes, pulmonary edema, thrombosis, and acute kidney injury. This paper reports a case of severe SCLS accompanied by acute tubular necrosis caused by hypoperfusion and myoglobinuria secondary to rhabdomyolysis, which resulted in chronic kidney disease that necessitated hemodialysis. However, there have been rare data of residual end-organ damage after acute attacks in Korea. Therefore, this paper reports a case of complicated SCLS enough to hemodialysis and that developed into chronic kidney disease.

Expression of Gpnmb in NK Cell Development from Hematopoietic Stem Cells

BACKGROUND: Molecular mechanisms of natural killer (NK) cell development from hematopoietic stem cells (HSCs) have not been clearly elucidated, although the roles of some genes in NK cell development have been reported previously. Thus, searching for molecules and genes related NK cell developmental stage is important to understand the molecular events of NK cell development. METHODS: From our previous SAGE data-base, Gpnmb (Glycoprotein non-metastatic melanoma protein B) was selected for further analysis. We confirmed the level of mRNA and protein of Gpnmb through RT-PCR, quantitative PCR, and FACS analysis. Then we performed cell-based ELISA and FACS analysis, to know whether there are some molecules which can bind to Gpnmb. Using neutralizing antibody, we blocked the interaction between NK cells and OP9 cells, and checked IFN-gamma production by ELISA kit. RESULTS: Gpnmb expression was elevated during in vitro developmental stage and bound to OP9 cells, but not to NK precursor cells. In addition, we confirmed that the levels of Gpnmb were increased at NK precursor stage in vivo. We confirmed syndecan4 as a candidate of Gpnmb's binding molecule. When the interaction between NK cells and OP9 cells were inhibited in vitro, IFN-gamma production from NK cells were reduced. CONCLUSION: Based on these observations, it is concluded that Gpnmb has a potential role in NK cell development from HSCs.