Chr9∶52042693|52047844⁃miR⁃351⁃5p⁃Pten Is Involved in the Development and Progression of Obstructive Sleep Apnea Syndrome through a ceRNA Mechanism / 中国生物化学与分子生物学报

Intermittent hypoxia (IH) is an important pathophysiological feature of obstructive sleep apnea (OSA), but its molecular mechanism is still unclear. We aim to investigate the role of endogenous competing endogenous RNA (ceRNA) regulatory network in the development of IH in OSA rats. An intermittent hypoxic rat model of OSA was constructed by hypoxic and reoxygenation cycles. CircRNAs and mRNAs were detected in rat bronchial tissues, and 230 up-regulated and 181 down-regulated circRNAs and 1238 up-regulated and 608 down-regulated mRNAs were analyzed and screened. The results of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differential circRNAs and mRNAs suggested that they were mainly associated with metabolic pathways and PI3K-Akt signaling pathways. The key circRNAs (the top six circRNAs with the largest differences) were further validated by quantitative real-time polymerase chain reaction (qRT-PCR), chr9:52042693| 52047844 and chr4: 64889575|64899587 were expressed in bronchial tissues consistent with the sequencing results, which were used to further construct the ceRNA regulatory network. Four potential ceRNA regulatory networks were identified by TargetScan and miRanda database, combined with the results of differential circRNA and mRNA. The expression of molecules in the four potential ceRNA regulatory networks was detected by qRT-PCR in bronchial and lung tissues, and the results suggested that the expression of this regulatory network, chr9:52042693|52047844-miR-351-5p-Pten, was consistent with the sequencing results. The findings indicate that chr9:52042693 | 52047844-miR-351-5p-Pten may be involved in the development and progression of obstructive sleep apnea syndrome through a ceRNA mechanism.

Anti-IH: An Innocuous Antibody Complicating Pre-Transfusion Testing

@#The positive antibody screen during pre-transfusion testing helps in the detection of clinically significant antibodies. However, sometimes clinically insignificant antibodies might perplex the serologic workup and can cause a delay in transfusion. Prompt recognition and timely resolution of these discrepancies in pre-transfusion testing, although time-consuming, is essential for the provision of safe blood to recipients. We report a case with an anti-IH antibody complicating the serological workup of pre-transfusion testing and an approach for its resolution and management. The role of transfusion medicine specialists in the characterization of antibodies and the selection of appropriate blood is paramount or warranted to promote safe transfusion practices.

Psychosis, Idiopathic Hypoparathyroidism and Basal Ganglia Calcification: A Case Report of Fahr’s Syndrome

Making a medical diagnosis in an elderly person presenting with first time psychiatric symptoms can be challenging. A 61 year old lady presented with 4 years history of tactile hallucinations in her legs and delusions of persecution, and 2 weeks history of depression and mild cognitive impairment. There were no other significant physical findings, except for dysarthria and fine bilateral hand tremors. As patient had no prior psychiatric history, she was investigated for differential diagnoses of late-onset schizophrenia, psychotic depression and early dementia. A thorough investigation for concomitant medical illnesses was done which revealed low serum calcium, high serum phosphate and relatively low serum parathyroid hormone levels. A diagnosis of Fahr’s syndrome (FS) was made based on history, hematological findings of idiopathic hypoparathyroidism and bilateral basal ganglia calcifications (BGC) on neuroimaging. Treatment of FS is non-specific and mainly symptomatic. This patient improved with treatment comprising antidepressant, antipsychotic and calcium supplement.

Evaluation of the Automated Blood Bank Systems IH-500 and VISION Max for ABO-RhD Blood Typing and Unexpected Antibody Screening

BACKGROUND: The use of automated systems for pre-transfusion tests is increasing in an attempt to reduce workload and the impact of human errors in blood banks. We evaluated the clinical performance of the automated blood bank systems IH-500 (Bio-Rad Laboratories, Switzerland) and VISION Max (Ortho-Clinical Diagnostics, USA) for ABO-RhD blood typing and unexpected antibody screening. METHODS: ABO-RhD blood typing was performed for 410 samples, and antibody screening was performed for 332 samples, including 15 antibody-positive samples. The results obtained from the two automated instruments were compared with those obtained using manual methods for ABO-RhD blood typing and a semiautomated method (DiaMed-ID system) for antibody screening. Additionally, both instruments were evaluated in terms of concordance rates, sensitivity, and carryover. RESULTS: The concordance rate of the ABO-RhD blood typing results between the manual methods and the two automated instruments was 100%. For antibody screening tests, the concordance rates between the semiautomated method (DiaMed-ID system) and the automated methods were 100% and 99.7% for the IH-500 and VISION Max instruments, respectively. The sole discrepant result was obtained for a sample identified as antibody-positive only on the VISION Max; the antibody was identified as anti-Le(a). The overall sensitivity of the two automated instruments was the same as or higher than that of the semiautomated method. Carryover was not observed in antibody screening. CONCLUSIONS: The IH-500 and VISION Max instruments showed reliable results for ABO-RhD blood typing and unexpected antibody screening, and can be used clinically, with confidence, for pre-transfusion tests in the blood bank.

Effects of administration of IH901, a ginsenoside intestinal metabolite, on muscular and pulmonary antioxidant functions after eccentric exercise

This study was conducted to investigate whether administration of IH901, a ginseng intestinal metabolite, ameliorates exercise-induced oxidative stress while preserving antioxidant defense capability in rat skeletal muscles and lung. Eight adult male Sprague-Dawley rats per group were randomly assigned to the resting control, exercise control, resting with IH901 (25, 50, and 100 mg/kg) consumption (R/IH901), or exercise with IH901 (25, 50, and 100 mg/kg) consumption (E/IH901) group. The trained groups ran 35 min 2 days/week for 8 weeks. To analyze the IH901-training interaction, serum biochemical analysis, lipid peroxidation, citrate synthase, protein oxidation, antioxidant and superoxide dismutase in skeletal muscles and lung tissue were measured. Compared to the exercise control group, animals that consumed IH901 had significantly increased exercise endurance times (p < 0.05) and decreased plasma creatine kinase and lactate dehydrogenase levels (p < 0.05), while those in the E/IH901 groups had increased citrate synthase and anti-oxidant enzymes and decreased lipid peroxidation and protein oxidation (p < 0.05). In conclusion, IH901 consumption in aging rats after eccentric exercise has beneficial effects on anti-inflammatory and anti-oxidant activities through down-regulation of pro-inflammatory mediators, lipid peroxidation, and protein oxidation and up-regulation of anti-oxidant enzymes.

A Novel Carbamoyloxy Arylalkanoyl Arylpiperazine Compound (SKL-NP) Inhibits Hyperpolarization-Activated Cyclic Nucleotide-Gated (HCN) Channel Currents in Rat Dorsal Root Ganglion Neurons

In this study, we determined mode of action of a novel carbamoyloxy arylalkanoyl arylpiperazine compound (SKL-NP) on hyperpolarization-activated cyclic nucleotide-gated (HCN) channel currents (Ih) that plays important roles in neuropathic pain. In small or medium-sized dorsal root ganglion (DRG) neurons (<40 microm in diameter) exhibiting tonic firing and prominent Ih, SKL-NP inhibited Ih and spike firings in a concentration dependent manner (IC50=7.85 microM). SKL-NP-induced inhibition of Ih was blocked by pretreatment of pertussis toxin (PTX) and N-ethylmaleimide (NEM) as well as 8-Br-cAMP, a membrane permeable cAMP analogue. These results suggest that SKL-NP modulates Ih in indirect manner by the activation of a Gi-protein coupled receptor that decreases intracellular cAMP concentration. Taken together, SKL-NP has the inhibitory effect on HCN channel currents (I h) in DRG neurons of rats.

Evaluation of IH-1000 for Automated ABO-Rh Typing and Irregular Antibody Screening / 대한수혈학회지

BACKGROUND: Despite modern advances in laboratory automated medicine, work-process in the blood bank is still handled manually. Several automated immunohematological instruments have been developed and are available in the market. The IH-1000 (Bio-Rad Laboratories, Hercules, CA, USA), a fully automated instrument for immunohematology, was recently introduced. In this study, we evaluated the performance of the IH-1000 for ABO/Rh typing and irregular antibody screening. METHODS: In October 2011, a total of 373 blood samples for ABO/Rh typing and 303 cases for unexpected antibody screening were collected. The IH-1000 was compared to the manual tube and slide methods for ABO/Rh typing and to the microcolumn agglutination method (DiaMed-ID system) for antibody screening. RESULTS: For ABO/Rh typing, concordance rate was 100%. For unexpected antibody screening, positive results for both column agglutination and IH-1000 were observed in 10 cases (four cases of anti-E and c, three of anti-E, one of anti-D, one of anti-M, and one of anti-Xg) and negative results for both were observed in 289 cases. The concordance rate between IH-1000 and column agglutination was 98.7%. Sensitivity and specificity were 90.9% and 99.3%, respectively. CONCLUSION: The automated IH-1000 showed good correlation with the manual tube and slide methods and the microcolumn agglutination method for ABO-RhD typing and irregular antibody screening. The IH-1000 can be used for routine pre-transfusion testing in the blood bank.

In vitro antioxidant properties of a ginseng intestinal metabolite IH-901 / 한국실험동물학회지

IH-901 (20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol or compound K) is a final intestinal bacterial metabolite of ginseng in humans. It has various pharmacologic effects such as antiaging, immunopotentiation, antistress, and antimetastatic activities. We analyzed the antioxidant activities of IH-901 using several assays including: total antioxidant activity, reductive potential, 1,1-diphenyl-2-picryl-hydrazyl, hydroxyl, superoxide and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assays, a nitric oxide scavenging assay and a lipid peroxidation assay. At concentrations of 25 and 100 microg/mL, IH-901 inhibited lipid peroxidation of a linoleic acid emulsion with a potency comparable to ascorbic acid and butylated hydroxyanisole. The reductive potential of IH-901 increased in a concentration-dependent manner. IH-901 exhibited strong DPPH, hydroxyl, superoxide and ABTS radical scavenging activities. IH-901 was also an effective inhibitor of lipid peroxidation, although IH-901 had only a mild scavenging activity against nitric oxide. These results suggest that IH-901 may be a useful antioxidant agent against reactive oxygen species.

Salvia miltiorrhiza monomer IH764-3 protects human brain microvascular endothelial cell from hypoxia/reoxygention injury through inhibiting leukocyte activity / 基础医学与临床

Objective To investigate the effect of IH764-3 on the leukocyte-mediated hypoxia-reoxygention injury of human brain microvascular endothelial cell (HBM VEC). Methods MTT assay was used to detect the survival of HBMVEC; gelatin zymography was used to check the activity of MMPs. The level of reactive oxygen species (ROS) in leukocyte was determined via commercially available kit, and the indirect enzyme-linked immunosorbent assay (ELISA) was used to quantify the contents of TNF-α, IL-1α, IL-2 and INF-γ in leukocyte culture medium. Results Survival of HBMVEC was impaired by hypoxia-reoxygenation, which was aggravated by supernatant of activated leukocytes but was attenuated by IH764-3. Leukocytes produced high level of MMP-9, ROS and cytokines (TNF-α, IL-1α, IL-2, IFN-γ) after hypoxia-reoxygenation, the process was inhibited by IH 764-3. Furthermore, IH764-3 could effectively reverse hypoxia-reoxygenation injury of HBMVEC with supernatant of activated leukocytes. Conclusion IH764-3 can protect HBMVEC from leukocyte-involved hypoxia-reoxygenation injury by attenuating the activation of leukocytes and inhibiting the pathogenic effects of leukocytes products.

A Case of ABO Discrepancy due to Anti-IH / 대한수혈학회지

The patient was a 70-year-old woman with hypertension and end stage renal disease, and she presented with left wrist pain due to falling a day before admission. On admission, laboratory testing revealed a hemoglobin level of 6.7 g/dL, and a physician ordered 2 units of packed RBCs. She had never received a RBC transfusion in the past. The ABO grouping showed a discrepancy between the cell type AB and serum type O, and the irregular antibody screening was negative. Crossmatchings with group AB and group O RBCs were incompatible. Anti-I, which is a cold antibody, was inferred because the degree of agglutination was decreased after warming. However, crossmatching with group O RBCs, which are the universal donor blood, was positive and the anti-IH was considered to be the specificity of the irregular antibody. The patient's serum did not react with group O cord (i) blood cells and anti-I was then considered. The genotype of this patient was AB, and it was inferred that the ABO discrepancy was due to anti-IH.

Salvia miltiorrhiza monomer IH764-3 protects human brain microvascular endothelial cell from hypoxia/reoxygention injury through inhibiting leukocyte activity / 基础医学与临床

Objective To investigate the effect of IH764-3 on the leukocyte-mediated hypoxia-reoxygention injury of human brain microvascular endothelial cell (HBMVEC). Methods MTT assay was used to detect the survival of HBMVEC; gelatin zymography was used to check the activity of MMPs. The level of reactive oxygen species (ROS) in leukocyte was determined via commercially available kit,and the indirect enzyme-linked immunosorbent assay (ELISA) was used to quantify the contents of TNF-?,IL-1?,IL-2 and INF-? in leukocyte culture medium.Results Survival of HBMVEC was impaired by hypoxia-reoxygenation,which was aggravated by supernatant of activated leukocytes but was attenuated by IH764-3. Leukocytes produced high level of MMP-9,ROS and cytokines (TNF-?,IL-1?,IL-2,IFN-?) after hypoxia-reoxygenation,the process was inhibited by IH 764-3. Furthermore,IH764-3 could effectively reverse hypoxia-reoxygenation injury of HBMVEC with supernatant of activated leukocytes. Conclusion IH764-3 can protect HBMVEC from leukocyte-involved hypoxia-reoxygenation injury by attenuating the activation of leukocytes and inhibiting the pathogenic effects of leukocytes products.

Effect of exogenous orexinA on different neurons in mouse prefrontal cortex prelimbic area / 第三军医大学学报

Objective To investigate the effect of exogenous orexinA on the pyramid neurons and interneurons in the prefrontal cortex prelimbic(PL)area.Methods The pyramid neurons and interneurons in PL area of Kunming mice were selected from prefrontal cortex slices by infrared visual patch clamp technique.The morphology and electrophysiological features of the pyramid neurons and interneurons were observed.The effect of exogenous orexinA at a concentration of 400 nmol/L on these cells was studied using the whole cell configuration.Results The pyramid neurons were large,pyramidal in cell body with clear apical dendrites extending vertically and several basal dendrites radiating.The interneurons were comparatively smaller and had several processes from cell body.In current clamp mode,all 54 pyramid neurons having been recorded showed frequency adaption,and the 15 recorded interneurons discharged rapidly and had no frequency adaption.While in vol-tage clamp mode,36 pyramid neurons were regarded as Ih(+)pyramid neurons for recorded hyperpolariztion-activated cation current,and the left 18 and 15 interneurons were Ih(-).Exogenous orexinA had a total reaction rate of 51.9% on 54 recorded pyramid neurons under current clamp,and a rate of 66.7% on 36 Ih(+)pyramid neurons and of 22.2% on the Ih(-)pyramid neurons under voltage clamp.All 15 recorded interneurons had no reaction to exogenous orexinA under either mode.Conclusion OrexinA plays excitatory effect on pyramid neurons in the prefrontal cortex PL area,and this effect is much more noticeable in pyramid neurons with Ih currents.

Combined Dexamethasone/Insulin-induced Hypoglyeemic Test in Manic and Schizophrenic Patients

Many investigators are trying to elucidate the pathogenesis of psychiatric disorders on the basis of neuroendocrine responses to stimulation or perturbation. Dexamethasone(DEX) suppression has been the most widely utilized as the prototypical challenge test. Dexamethasone suppression test(DST) has proven to be valuable in diagnosing the depressive spectrum disorder. Reported specificity of diagnosis of depression is relatively high, but sensitivity is limited. Some researchers used the combination of dexamethasone and corticotropin releasing hormone(CRH) in order to improve the sensitivity. They reported that combined DEX/CRH test, i.e., we administered the insulin instead of CRH. Total subjects were 28(7 normal controls, 10 manic patients, 11 schizophrenic, patients). Subject were token DEX(1.5mg p.o.) at 11 p.m., insulin 16 hours later(0.1 unit/kg i.v.). Five blood samples for the determination of cortisol and ACTH were serially drawn at 15 minute interval. The results are as following : 1) The cortisol an ACTH levels of manic subjects increased following insulin administration. Manic subjects showed higher levels of cortisol and ACTH than schizophrenic and normal control subjects. The cortisol and ACTH levels of schizophrenic and normal control subjects did not show gross changes. 2) The sensitivity of the test was lower than that of reported DEX/CRH test.