Exaggerated response to cold stress in a congenic strain for the quantitative trait locus for blood pressure

OBJECTIVE: Stroke-prone spontaneously hypertensive rats (SHRSP) are known to have sympathetic hyperactivity to various stimuli. In the search for 'intermediate phenotypes' inferring the function of hypertension genes, the present study assessed responsiveness to cold stress in a congenic strain derived from SHRSP/Izm and Wistar-Kyoto/Izm (WKY/Izm). DESIGN: A congenic strain, WKYpch1.0, was established by 10 generations of backcrossing to transfer the chromosomal fragment between D1Wox29 and D1Arb21 of SHRSP to WKY. This fragment covered the 100:1 confidence interval of the quantitative trait locus (QTL) for blood pressure identified in a previous study. Response to cold stress was studied by exposing rats to 4 degrees C for 4 h. Blood pressure was monitored with telemetry. Urine was collected during the exposure, and urinary concentrations of catecholamines were measured by high-performance liquid chromatography. RESULTS: Under the cold stress, urinary excretion of norepinephrine (NE) and vanillylmandelic acid (VMA), as well as the plasma level of NE, was significantly greater in WKYpch1.0 than in WKY. The increase in blood pressure during the cold stress was also greater in WKYpch1.0 than in WKY. Further, neonatal chemical sympathectomy using guanethidine abolished the exaggerated response in blood pressure and in urinary excretion of NE and VMA in WKYpch1.0. CONCLUSION: These results suggested that the QTL region on rat chromosome 1 harbored genes responsible for the exaggerated response of the sympathetic nervous system to the cold stress. The relationship of this with the pathogenesis of hypertension should be elucidated in future studies.     

Lectin-like oxidized LDL receptor-1 is a cell-adhesion molecule involved in endotoxin-induced inflammation

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a major endothelial receptor for oxidized low-density lipoprotein, and is assumed to play a proatherogenic role in atherosclerosis. LOX-1 expression is induced by inflammatory cytokines as well as by proatherogenic stimuli. LOX-1 protein binds agedapoptotic cells, activated platelets, and bacteria, suggesting that it may have diverse activities in vivo. Here, we reveal a role for LOX-1 in endotoxin-induced inflammation. In a model of endotoxemia, injection of a high dose of endotoxin into rats induced leukopenia within 1 h and death of the animals within 24 h. Preadministration of anti-LOX-1 antibody reduced the degree of leukopenia and completely rescued the animals, whereas control IgG did not. In a model of low-dose endotoxin-induced uveitis, anti-LOX-1 antibody efficiently suppressed leukocyte infiltration and protein exudation. In situ videomicroscopic analyses of leukocyte interactions with retinal veins revealed that anti-LOX-1 antibody reduced the number of rolling leukocytes and increased the velocity of rolling, suggesting that LOX-1 functions as a vascular tethering ligand. The ability of LOX-1 to capture leukocytes under physiologic shear was confirmed in an in vitro flow model. Thus, LOX-1 is an adhesion molecule involved in leukocyte recruitment and may represent an attractive target for modulation of endotoxin-induced inflammation.     

Erythropoiesis during an erythroblastic phase of chronic myeloproliferative disorder associated with monosomy 7

A chronic myeloproliferative disorder associated with monosomy 7 is described in a 3 1/2-year-old boy. His presenting features closely resembled those of juvenile chronic myeloid leukaemia (JCML). Cytogenetic study of bone marrow cells showed that all of the metaphases examined had chromosome 7 deletions. He developed an erythroblastic phase, characterized by anaemia, marked erythroid hyperplasia of bone marrow and the appearance of nucleated red blood cells in the peripheral blood. During the erythroblastic phase, blood transfusion resulted in a suppression of erythropoiesis as evidenced in both the peripheral blood and bone marrow. The in vitro culture studies showed that the erythroid precursor was dependent upon erythropoietin (Ep) for differentiation and proliferation during the erythroblastic phase. However, the Ep dose-response curve showed that a peak of erythroid colony formation occurred at a lower concentration than in the healthy controls. These findings suggest that although the erythroid precursor remains under the control of Ep, it has an increased sensitivity to Ep during the erythroblastic phase of monosomy 7.     

Beneficial effects of combination of ACE inhibitor and angiotensin II type 1 receptor blocker on cardiac remodeling in rat myocardial infarction

OBJECTIVE: Angiotensin-converting enzyme (ACE) inhibitor and angiotensin II type I receptor blockers (ARB) prevent cardiac remodeling after myocardial infarction (MI). However, it is controversial whether combination therapy of ACE inhibitor and ARB is more effective on cardiac remodeling than each agent alone. In this study, we compared the effects of an ACE inhibitor (temocapril), an ARB (CS-866), and their combination on cardiac remodeling after MI. METHODS: Temocapril at 3 or 30 mg/kg/day, CS-866 at 1 or 10 mg/kg/day, or combined temocapril and CS-866 at 1.5 and 0.5 mg/kg/day or at 15 and 5 mg/kg/day, respectively, were administered to rats after MI. At 4 weeks after MI, we assessed hemodynamics, cardiac function by Doppler echocardiography and non-infarcted myocardial mRNA expression. RESULTS: Animals treated with a combination of the two drugs had hemodynamics, heart weights and dimensions similar to the other treated animals. However, the combination of the two drugs suppressed ANP, BNP and other gene expressions related to contractile proteins of fetal type and collagens more effectively than ACE inhibitor or ARB alone. CONCLUSION: These data suggest that combination of the two drugs, independent of the hemodynamic effect, may improve left ventricular phenotypic change, collagen accumulation and diastolic function.     

Surgical resection of malignant lymphoma in the right atrium after systemic chemotherapy

A 74-year-old man was referred to us for evaluation of a tumor in the right atrium (RA). Transesophageal echocardiography (TEE) showed an unmovable 50x60 mm mass in the RA. Based on histological findings of subcutaneous tumors in the right abdominal wall, he was diagnosed as malignant lymphoma (ML), and treated with a THP-COP regimen. Upon completion of first THO-COP therapy, TEE showed marked regression of the mass and division into 3 masses, one of which showed marked floating movement with a small stalk. To prevent the risk of embolic events, surgical resection was performed. Resected tumors were necrotic tissues. Serial imaging of cardiac tumor and surgical resection is desirable to decrease the possibility of embolic complication.     

Hinesol,a compound isolated from the essential oils of Atractylodes lancea rhizome,inhibits cell growth and induces apoptosis in human leukemia HL-60 cells

Hinesol is a unique sesquiterpenoid isolated from the Chinese traditional medicine, Atractylodes lancea rhizome. In a previous study, we screened various natural products in human leukemia HL-60 cells and identified an essential oil fraction from A. lancea rhizome that exhibited apoptosis-inducing activity in these cells; hinesol was subsequently shown to be the compound responsible for this apoptosis-inducing activity. In this study, we describe the cytotoxic effects and molecular mechanisms of hinesol in HL-60 cells. The antitumor effect of hinesol was associated with apoptosis. When HL-60 cells were treated with hinesol, characteristic features of apoptosis, such as nuclear fragmentation and DNA fragmentation, were observed. These growth-inhibitory and apoptosis-inducing activities of hinesol in leukemia cells were much stronger than those of β-eudesmol, another compound isolated from the essential oil fraction. Furthermore, hinesol induced activation of c-Jun N-terminal kinase (JNK), but not p38, prior to the onset of apoptosis. These results suggested that hinesol induced apoptosis through the JNK signaling pathway in HL-60 cells. Therefore, hinesol may represent a novel medicinal drug having indications in the treatment of various cancers, including leukemia.

     

Clinical characteristics of COVID-19 patients with underlying rheumatic diseases in Japan: data from a multicenter observational study using the COVID-19 Global Rheumatology Alliance physician-reported registry

Clinical Rheumatology - To describe clinical characteristics of patients in Japan with coronavirus disease 19 (COVID-19) and pre-existing rheumatic disease and examine the possible risk factors...     

Calcium mobilization in liver transplantation graft with warm ischemia

The influence of warm ischemia on calcium mobilization in liver transplantation was investigated. Twenty-four porcine orthotopic liver transplantations were performed by a temporary portal arterialization technique. Swine were divided into three groups according to warm ischemia time; I (0 min,n=9), II (30 min,n=8), and III (60min,n=7). Ionized calcium was measured in arterial and hepatic venous blood, in initial perfusate, and in initial perfused blood. In group I, all the pigs survived, while in group III all succumbed. In group II, four survived and four died. Ionized calcium level in influx showed no differences, but the level in the initial perfusate in group I was significantly higher than that in group III. The level in the initial perfused blood in group I was significantly higher than levels in groups II and III. Retrospective analysis in group II showed that ionized calcium value in the initial perfused blood in the survivors was significantly higher than that in the non-survivors. A substantial amount of ionized calcium accumulated after revascularization in the graft loaded with warm ischemia, and, in group II, significantly more ionized calcium accumulated in the non-survivors.     

Differences in the effects of 20 K- and 22 K-hGH on water retention in rats.

Antidiuretic actions induced by two growth hormone (GH) isoforms (20 K- and 22 K-hGH; 0.2 and 2.0 mg/kg) were evaluated in rats, as fluid retention may cause oedema, one of the adverse effects of GH. Both GH isoforms (2.0 mg/kg) suppressed urine excretion in hypophysectomized rats (P< 0.01), but only the 22 K-hGH isoform (2.0 mg/kg) suppressed urine excretion in intact rats (P< 0.01). In addition, prolactin (PRL) suppressed urine excretion in intact rats (P< 0.05). In conclusion, 20 K-hGH has less potency in causing urine retention than 22 K-hGH and since 20 K-hGH is missing 15 amino acids found in 22 K-hGH, these amino acids may be important for the antidiuretic action of GH. Since prolactin suppressed urine excretion, a part of the antidiuretic action of GH may be related to PRL-R activation.     

Quantification of Myocardial Perfusion Defect Size in Rats: Comparison between Quantitative Perfusion SPECT and Autoradiography

Purpose

Ultra-high resolution single-photon emission computed tomography (SPECT) system, using multiple pinhole collimators, has been applied to the imaging of small rodents. We aimed to compare the myocardial infarction (MI) area on quantitative perfusion single-photon emission computed tomography (QPS; Cedars-Sinai Medical Center, USA) with that on high-resolution autoradiography in rat model to determine the accuracy of perfusion defect measurement by QPS.

Procedures

After thoracotomy, rats (n?=?9) had their left coronary arteries occluded and reperfused before injection with 185 MBq [^99mTc] methoxyisobutylisonitrile ([^99mTc]MIBI) for SPECT and autoradiography. Healthy rats (n?=?28) were similarly scanned to create a normal database on which to base QPS. The MI area on SPECT images was analysed automatically by QPS software. For the autoradiography images, regions of interest for MI were set at 1 mm intervals.

Results

In normal rats, [^99mTc]MIBI accumulated throughout the left ventricles, and a polar map of ventricular perfusion showed the lowest and highest uptakes in the inferior (68 %?±?4 %) and anterior (92 %?±?5 %) walls, respectively. In the rat MI model, the percentage of polar map with reduced [^99mTc]MIBI uptake correlated strongly with the percentage of left ventricle with MI on autoradiography (r²?=?0.90).

Conclusions

QPS can quantitatively evaluate MI severity on myocardial perfusion images in rats, with comparable results to autoradiography. This widely available software could promote the development of new techniques for analysing cardiac images in small animals.