Involvement of Estrogen Receptor-α in the Activation of Nrf2-Antioxidative Signaling Pathways by Silibinin in Pancreatic β-Cells

Silibinin exhibits antidiabetic potential by preserving the mass and function of pancreatic β-cells through up-regulation of estrogen receptor-α (ERα) expression. However, the underlying protective mechanism of silibinin in pancreatic β-cells is still unclear. In the current study, we sought to determine whether ERα acts as the target of silibinin for the modulation of antioxidative response in pancreatic β-cells under high glucose and high fat conditions. Our in vivo study revealed that a 4-week oral administration of silibinin (100 mg/kg/day) decreased fasting blood glucose with a concurrent increase in levels of serum insulin in high-fat diet/streptozotocin-induced type 2 diabetic rats. Moreover, expression of ERα, NF-E2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in pancreatic β-cells in pancreatic islets was increased by silibinin treatment. Accordingly, silibinin (10 μM) elevated viability, insulin biosynthesis, and insulin secretion of high glucose/palmitate-treated INS-1 cells accompanied by increased expression of ERα, Nrf2, and HO-1 as well as decreased reactive oxygen species production in vitro. Treatment using an ERα antagonist (MPP) in INS-1 cells or silencing ERα expression in INS-1 and NIT-1 cells with siRNA abolished the protective effects of silibinin. Our study suggests that silibinin activates the Nrf2-antioxidative pathways in pancreatic β-cells through regulation of ERα expression.

Effect of Shexiang Baoxin Pills on isoprenaline-induced myocardial cell hypertrophy and Cx43 expression / 中南大学学报(医学版)

Objective:To observe the effects of Shexiang Baoxin Pill (SBP) on isoprenaline (Iso)-induced changes in myocardial cell volume,shape,and connexin 43 (Cx43) expression.Methods:HgC2 myocardial cells were randomly divided into a control group,a Iso group and a Iso+SBP group.After 72 h of culture,the average surface area of HgC2 cells was measured under phase contrast microscope.Bicinchoninic acid (BCA) protein assay was carried out to determine the concentration of proteins.The survival rate of myocardial cells was measured by methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay,and the Cx43 expression was detected by Western blot.Results:The mean surface area and Cx43 concentration in Iso-treated myocardial cells were increased under the phase contrast microscope (P<0.05).Compared with the Iso group,the mean surface area was decreased,and the Cx43 concentration was reduced in the Iso+SBP group (both P<0.05).Compared with the control group,the Cx43 expression was obviously down-regulated in the H9C2 cells of the Iso group (P<0.05);while compared with the Iso group,the Cx43 expression was obviously up-regulated in the Iso+SBP group (P<0.05).Conclusion:Shexiang Baoxin Pills can prevent Iso-induced myocardial hypertrophy and down-regulate Cx43 expression.

Correlation between serum leptin level with coronary heart disease risk stratification and lesion degree of coronary artery / 重庆医学

Objective To observe the change of serum leptin in different risk stratifications of coronary heart disease (CHD) and to investigate its relationship with the severity of coronary artery lesion and the coronary artery Gensini score and its value in the coronary heart disease risk stratification .Methods According to coronary angiography ,120 research subjects were enrolled and di-vided into 4 groups :the non-CHD group ,stable angina(SAP) group ,unstable angina pectoris(UAP) group and myocardial infarc-tion group(AMI) ,respectively .The serum leptin levels in 4 groups were determined by immunoassay and the correlation between the leptin level with the coronary heart disease risk factor and biochemical markers of risk assessment was analyzed .Results The serum leptin level in the AMI group was significantly higher than that in the non-CHD group and the SAP group ,the leptin level showed the increasing trend with the increase of the coronary lesion severity and the Gensini scores and was positively related with the CHD risk stratification indicators cTnT and smoking index ,and negatively related with blood uric acid .Conclusion The serum leptin may be used as the valuable marker for evaluating the occurrence of acute coronary event and has good correlation with usual biochemical markers of CHD risk stratification and the severity of coronary artery lesion .

The expression of hypoxia-inducible factor-1alpha and its hydroxylases in pulmonary arteries of patient with chronic obstructive pulmonary disease / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe the expression of hypoxia-inducible factor-lalpha subunit (HIF-1alpha), HIF prolyl hydroxylase domain-containing protein(PHDs) and factor inhibiting HIF-1(FIH) in pulmonary arteries of patient with chronic obstructive pulmonary disease (COPD).</p><p><b>METHODS</b>Pulmonary specimens were obtained from patients undergoing lobectomy for lung cancer, 12 had concurrent COPD (COPD group) and 14 without COPD (control group). The ratio of vascular wall area to total vascular area (WA%) and pulmonary artery media thickness (PAMT) was observed, and HIF-1alpha and its hydroxylases(PHD1, PHD2, PHD3, FIH) mRNA and protein were detected by in situ hybridization and immunohistochemistry respectively.</p><p><b>RESULTS</b>WA% and PAMT of COPD patients(50 microm +/- 9 microm, 40% +/- 5%, were statistically different from those of the control subjects (39 microm +/- 6 microm, 31% +/- 4%, P < 0.01). Relative quantification of mRNA and protein levels (absorbance, A) showed that HIF-lalpha mRNA and protein levels in COPD group (0.230 +/- 0.036,0.275 +/- 0.039) were statistically higher than those of the control subjects (0.174 +/- 0.029, 0.102 +/- 0.015, P < 0.01 ), and that the protein level increased more markedly. PHD1 mRNA in COPD subjects (0.180 +/- 0.030) was comparable to that in control group (0.191 +/- 0.029, P > 0.05); PHD2 and PHD3 mRNA levels in COPD (0.245 +/- 0.044, 0.252 +/- 0.023) were significantly higher than those in control group(0.182 +/- 0.028, 0.127 +/- 0.017, P < 0.01). On the other hand, in COPD subjects PHD1 protein (0.104 +/- 0.015) was significantly lower(P < 0.01), whereas PHD2 protein (0.274 +/- 0.044) was significantly higher(P < 0.01) than those in control group(0.209 +/- 0.023, 0.219+/- 0.043). As for PHD3 protein, no significant changes were observed between the two groups (0.161+/- 0.023 in COPD, 0.146 +/- 0.021 in control, P > 0.05). FIH mRNA and protein both showed no differences between the two groups. Linear correlation analysis showed that HIF1alpha protein was positively correlated with WA%, PAMT, PHD2 mRNA and protein, PHD3 mRNA, and that HIF1alpha protein was negatively correlated with PHD1 protein.</p><p><b>CONCLUSION</b>PHDs may be involved in the process of hypoxic pulmonary vascular remodeling in COPD via regulation of HIF-1alpha gene expression</p>

Effects of nitric oxide on spontaneous pain reaction and neuronal apoptosis in the spinal cord of rats induced by formalin inflammatory pain / 中国应用生理学杂志

<p><b>OBJECTIVE</b>To observe whether formalin inflammatory pain can induce neuron apoptosis in rats spinal cord or not and the effects of nitric oxide on the spontaneous pain reaction and neuron apoptosis in the spinal cord of rats with formalin inflammatory pain.</p><p><b>METHODS</b>Formalin-induced paw licking time was used to reflect the degree of spontaneous pain of rats, and the flow cytometry was used to detecte neuron apoptosis rate of spinal cord.</p><p><b>RESULTS</b>Compared with control group, the apoptosis ratio of spinal neuron was increased in the rats with formalin inflammatory pain, and peaked at 3d after formalin injection. Pre-intrathecal injection of NOS inhibitor L-NAME inhibited the nociceptive behavioural response in double phases induced by fonnrmalin injection and cut down the neuron apoptosis ratio of spinal cord of rats with formalin inflammatory pain. Nociceptive behavioural response and incraesed neuron apoptosis in the spinal cord were induced by intrathecal injection of L-Arg in normal rats.</p><p><b>CONCLUSION</b>The results indicated that formalin inflammatory pain could induce the apoptosis of spinal neurons. The neurons apoptosis was the most significant on the third day after formalin injection. The increased pruduction of NO in spinal cord could promote the transmit of nociceptive information and participate the induction of neuronal apoptosis during the formalin inflammatory pain.</p>

Ground-based observations of ultraviolet and total solar radiation in Shenyang, northeast China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>This work explores the diurnal variation of Solar ultraviolet radiation (UVR) and total solar radiation (TSR) in northeast China, using daily observations of UVR and TSR in Shenyang.</p><p><b>METHODS</b>UVR and TSR measurements were carried out from March 1st, 2006 to December 31st, 2009 in Shenyang, Liaoning province, China (41°51' N, 123°27' E).</p><p><b>RESULTS</b>Both TSR and UVR showed seasonal variation, reaching the highest levels in summer and the lowest in winter. They showed the greatest fluctuation in summer and autumn. The irradiance of TSR and UVR on clear days around the equinoxes and solstices increased substantially compared with the mean seasonal irradiance, especially in autumn. The whole day accumulated dose of UVR in winter was far less than that during the middle part of a summer day (i.e. between 10:00 and 14:00). It was also less than the accumulated summer dose of morning and afternoon (i.e. between 8:00 and 10:00 and 14:00 and 16:00).</p><p><b>CONCLUSION</b>The instant irradiance and daily accumulated amount of UVR are low in Shenyang, especially in autumn and winter. Thus concern about the health effects arising because shortage of UVR in northeast China is warranted.</p>

Formalin inflammatory pain induced hippocampal neuronal apoptosis of rats / 中国应用生理学杂志

<p><b>AIM</b>To investigate whether formalin inflammatory pain can induce hippocampal neuronal apoptosis of rats or not.</p><p><b>METHODS</b>Rats were subcutaneously injected with 0.2 ml 0.5% formalin into the ventral surface of right hind paw to induce periphery inflammatory pain. The flinches of rats were counted to observe their painful reaction. Flow cytometry was used to assay the ratio of apoptosis of hippocampal neurons. The immunohistochemistry was used to observe the expression of p53 protein in hippocampal subregions.</p><p><b>RESULTS</b>Compared with control group, the apoptotic ratio of hippocampal neurons was significantly increased in rats with inflammatory pain, and formalin inflammatory pain induced upregulation of p53 protein expression in all hippocampal subregions. Both the apoptotic ratio and the p53 protein expression peaked on the third day after the formalin injection. The twice injection of formalin into the hind paws of rats resulted in an enhancement of painful reaction and increase in apoptotic ratio of hippocampal neurons compared with the rats of injection formalin once group.</p><p><b>CONCLUSION</b>Formalin inflammatory pain can induce the hippocampal neuronal apoptosis in rats with a certain time course. Neuronal apoptosis is relevant to the intensity of pain. The up-regulation of p53 protein expression may implicate in the induction of hippocampal neuronal apoptosis in rats with inflammatory pain.</p>

Intrathecal injection of MK-801 inhibited the NOS activity and NO content of hippocampus in rat during the process of formalin-induced inflammatory pain / 中国应用生理学杂志

<p><b>AIM</b>To study the effect of intrathecal injection of MK-801, a NMDA receptor antagonist, on the NOS activity and NO content of hippocampus in rat during the process of formalin-induced inflammatory pain as well as the pain behavior of rat.</p><p><b>METHODS</b>The degree of pain was determined by observing the time of licking and biting the injected paw. NOS expression in the hippocampus was determined by using NADPH-d histochemical staining. NO content of hippocampus was determined by assaying NO3; and NO2.</p><p><b>RESULTS</b>Subcutaneous injection of formalin elicited a characteristic pain behavioural response consisting of licking and biting the injected paw, etc. Intrathecal injection of MK-801 could shorten obviously the time of licking and biting representing pain behavioural response in phase 2. It is suggested that intrathecal injection of MK-801 could block the pain behavioural response induced by formalin (P < 0.05). The number and staining degree of NADPH-d positive neurons in formalin group significantly increased at 12 h after the formalin injection in CA1, CA2-3 and DG of hippocampus compared with control group as well as NO content, however, the number and staining degree of NADPH-d positive neurons in formalin + MK-801 group significantly decreased in contrast to those of formalin 12 h group as well as the NO content (P < 0.01).</p><p><b>CONCLUSION</b>Intrathecal injection of NMDA receptor antagonist MK-801 could inhibit the NOS activity and NO production in hippocampus of rat, which showed the increase of hippocampal NO production was mainly induced by the peripheral nociceptive information input.</p>

Osteonecrosis of the Hip in Patients with Aplastic Anemia

The incidence and clinical and magnetic resonance imaging features of osteonecrosis of the hip were evaluated in patients with aplastic anemia. Two hundred and forty-one patients with aplastic anemia were examined using MR imaging of bone marrow during the five years from 1994 to 1998. Osteonecrosis of the hip was observed on MR imaging in nineteen (15 males and 4 females, mean age 35 yr) of the 241 patients. It was present in both hips in 14 patients, and there were five cases with unilateral occurrence, with a total of 33 involved hips. All except for five hips with associated bone marrow edema revealed increased fatty marrow conversion in the proximal femoral metaphysis. In nine patients, osteonecrosis was detected without any pain. Five patients already had osteonecrosis before any medication was administered. Twelve patients received antilymphocyte globulin, and seven patients received a low dose of steroids before the MR diagnosis of osteonecrosis. Osteonecrosis of the hip frequently develops in patients with aplastic anemia (7.9%), associated with fatty marrow conversion of the proximal femoral metaphysis.

A Clinical Observation on Leukemia Cutis / 대한피부과학회지

BACKGROUND: Leukemia cutis is readily recognized and documented by biopsy, in contrast. to leukemic involvement in more occult sites. Nine cases of leukemia cutis have been reported in the Korean literatures. However no collective clinical studies have been reported in Korea. OBJECTIVE: We evaluated the differences in patient age and sex, the clinical appearences and distributions of the skin lesions, interval between diagnosis of systemic leukemia and skin involvement, clinical course, and prognosis according to the type of leukemias. METHODS: We carried out a retvospective study of 22 cases of leukemia cutis. Clinical information was obtained from the records of of 22 patients diagnosed at St. Mary's Hospital from 1988 to 1995. All the included cases were well evaluated for their clinical and histopathologic findings. RESULTS: 1. Among 22 patients with leukemia cutis, male patients outnumbered female by 2 to 1 and the mean age was 25.8 years. 2. The clinical appearance of leukemia cutis includes papules, macules, nodules, plaques in all types of leukemia. Ulcerative lesions and vesicles were seen infrequently in leukemia cutis. Leukemia cutis often involved saultiple location of the skin, with no specific predilection of the site. There were no differences in distribution of lesions depending on the types of systemic leukemia. 3. In 68% of the patients with leukemia cutis, the skin lesions developed after the systemic leukemia was diagnosed, and 14% of patients had concomitant, involvement. 18% of patients had skin lesions preceding the diagnosis of systemic leukemia, howevere cytochemical and cytomorphologic studies of bone marrow and peripheral blood smear were not employed at the time of the skin biopsy. 4. Fourteen of 22 patients(64%) did not achieve a complete remission following the diagnosis of leukemia cutis and two of 14 patients without having complete remission could achieve complete remissions with proper anticancer therapy after the diagnosis of leukemia cutis. Total eight patients(36%) achieved a complete remission, then they had a relapse of leukemia in the skin, without having had any skin involvement at the time of the diagnosis of leukemia. 5. Seventeen of 22 patients(77% ) who were being followed up in our series died after leukemia cutis was diagnosed. The mean intervals between diagnosis of leukemia cutis and death was 3.8 months and they died mostly within 1 year. CONCLUSION: The presence of leukemic infiltration in the skin may help the clinician suspect the early diagnosis and relapse of systemic leukemia. It appears that leukemia cutis is associated with a grave prognosis.

Effect of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) on Neutropenia Occuring during Radiotherapy / 대한치료방사선과학회지

PURPOSE: To assess the efficacy of recombinant human granulocyte-macrophage colony-stimulatin g factor(GM-CSF) in the neutropenia by radiotherapy. MATERIALS AND METHODS: Eleven patients with various solid tumor were treated with a daily subcutaneous dose of GM-CSF(3-7 microgram/kg) for 5 days during the radiotherapy. Before and during the course of the study all the patients were monitored by the recording of physical examination, the complete blood count with differential and reticulocyte count and liver function test. Eight patients received patients received prior or concurrent chemotherapy. RESULTS: In 10 patients, the neutrophilic nadir was significantly elevated and the length of time that patients had a neutrophil count below 103/mm3, a threshold known to be critical to acquiring infective complications was shortened following GM-CSF injection. A significant rise (two fold or greater) of neutrophil count was seen in 10 of 11 patients. In most patients, discountinuation of GM-CSF resulted in a prompt return of granulocyte counts toward baseline. However the neutrophil count remained elevated over 103/mm3 during radiation therapy, and radiotherapy delays were avoided. Other peripheral blood components including monocytes and platelets also increased after GM-CSF treatment. No siginificant toxicity was encountered with subcutaneous GM-CSF treatment. CONCLUSION: GM-CSF was well tolerated by subcutaneous route and induced improvement in the neutropenia caused by radiotherapy.

Richer's Syndrome: Report of a case

Richer's syndrome is a development of a high grade malignant lymphoma in a patient with preexisting chronic 1ymphocytic leukemia, small lymphocytic lymphoma or Waldenstrom's macroglobulinemia. A rare case of Richer's syndrome arising in the spleen of a 35-year-old-man was studied by morphology, immunohistochemistry and gene rearrangement study. He has had weight loss and night sweat for last 6 months. Hepatosplenomegaly and abdominal lymphadenopathy were noted on CT scanning. Especially an ovoid radiolucent mass was found within the image of splenomegaly. Lymph nodes and liver biopsy, bone marrow aspiration and splenectomy were done. In the lymph nodes, liver and bone marrow, well differentiated small lymphocytic infiltrations were found but, in the spleen, pleomorphic, large cells with occasional multinucleated giant cells formed a nodular mass surrounded by diffuse, extensive infiltration of small well differentiated lymphocytes. The two distinctive areas in the spleen had positive staining for B-cell marker (HLA-DR and L26), negative staining for T-cell marker (UCLH1), and positive staining for IgM heavy chain and kappa light chain by immuohistochemical study. so this case was diagnosed as a diffuse large cell 1ymphoma transformed from small lymphocytic lymphoma. We made an another effort to clarify their clonality. Gene rearrangement method usingcomplementarity.determining region 3(CDR3) of immunoglobulin heavy chain (IgH) gene and T-cell receptor gamma (TCRgamma) gene by polymerase chain reaction (PCR) technique was done. The two lymphomas in the spleen demonstrated the same rearrangement pattern in both IgH and TCRgamma gene. We think these findings strongly suggest that the large cell lymphoma has the same clonality with that of the small lymphocytic lymphoma.

A Case of Acute Graft-versus-Host Disease / 대한피부과학회지

We report a case of acute graft-versus-host disease, which developed after bone marrow transplantation because of acute myelocytic leukemia in a 39-year old male, The pruritic, erythematous maculopapular eruptions began to developed on the perioral regions, and spreaded the face, the oral mucosa, both hands, and buttocks at the twenty fourth day after bone marrow transplanta.tion. The eruptions were confluent to form erythematous patches. Iistopathological findings show parakeratosis, lymphoid cell exocytosis, and papillary edema, lymphohistiocytic infiltration, and melanophage in the upper dermis, and basal vacuolation. He was treated systemically by methylprednisolone, and antilymphocytic globulin, and tapically by emollients and steroids.