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Biomedical subjects

W Zhao

Publications and source records attributed to W Zhao.

At least 199 records · Page 11Linked to original sources

Bone resorption induced by parathyroid hormone is strikingly diminished in collagenase-resistant mutant mice.

Parathyroid hormone (PTH) stimulates bone resorption by acting directly on osteoblasts/stromal cells and then indirectly to increase differentiation and function of osteoclasts. PTH acting on osteoblasts/stromal cells increases collagenase gene transcription and synthesis. To assess the role of collagenase in the bone resorptive actions of PTH, we used mice homozygous (r/r) for a targeted mutation (r) in Col1a1 that are resistant to collagenase cleavage of type I collagen. Human PTH(1-34) was injected subcutaneously over the hemicalvariae in wild-type (+/+) or r/r mice four times daily for three days. Osteoclast numbers, the size of the bone marrow spaces and periosteal proliferation were increased in calvariae from PTH-treated +/+ mice, whereas in r/r mice, PTH-induced bone resorption responses were minimal. The r/r mice were not resistant to other skeletal effects of PTH because abundant interstitial collagenase mRNA was detected in the calvarial periosteum of PTH-treated, but not vehicle-treated, r/r and +/+ mice. Calcemic responses, 0.5-10 hours after intraperitoneal injection of PTH, were blunted in r/r mice versus +/+ mice. Thus, collagenase cleavage of type I collagen is necessary for PTH induction of osteoclastic bone resorption.

Animals↗

Sudden death in a rat subarachnoid hemorrhage model.

The pathogenesis of sudden death during subarachnoid hemorrhage (SAH) still remains to be elucidated. A new rat common carotid artery-prechiasmal extracorporeal shunt model was designed to study the effect of different severities of SAH on intracranial pressure (ICP), regional cerebral blood flow (rCBF), and mortality. Different severities of SAH were induced by controlling the bleeding period (from 30 to 90 sec) and number of bleedings (one or three times). SAH caused a dramatic increase in ICP and immediate depression of rCBF, which recovered slowly to a certain extent. ICP increased sharply within the first 30 seconds and reached a plateau concomitant with nearly zero rCBF, which suggested the occurrence of cerebral circulation arrest. Bleeding of more than 60 seconds and increased ICP over 80 mmHg were directly correlated with the mortality. Respiratory arrest was the first sign of death, immediately followed by cardiac depression resulting in sudden death. This model combines arterial bleeding with systemic blood pressure and controlled bleeding time to simulate the acute period of SAH.

Acute Disease↗

The putative mechanistic basis for the modulatory role of endothelin-1 in the altered vascular tone induced by Trypanosoma cruzi.

Chagas' disease, caused by Trypanosoma cruzi, is an important cause of heart disease in Latin America. T. cruzi-induced microvascular compromise, in turn, is thought to play a major role in chagasic heart disease. Previous in vitro studies have implicated endothelin-1 (ET-1) as a potentially important vasomodulator present in increased levels in the supernatant of T. cruzi infected cultured human umbilical vein endothelial cells (HUVEC). Thus, the goal of the present investigation was to further evaluate the potentially important contribution of ET-1 to T. cruzi-induced alterations in vascular tone in vitro. Bioassay studies once again documented that exposure of isolated rat aortic rings to infected HUVEC supernatants elicited contractile responses whose steady-state magnitude was significantly greater than contractile responses elicited by exposure of aortic rings to uninfected HUVEC supernatants. Furthermore, the increased aortic contractility was significantly attenuated by the presence of the ET(A) subtype selective antagonists BMS-182,874 or BQ-123. Additionally, incubation of HUVEC with either verapamil or phosphoramidon prior to infection was also associated with reduced aortic contractility, upon exposure to the supernatant. Phosphoramidon, but not verapamil, produced a significant decrease in the measured ET-1 levels in the HUVEC supernatant. Consistent with the bioassay results, preincubation of Fura-2-loaded cultured rat aortic vascular smooth muscle cells with verapamil resulted in a near complete ablation of ET-1-induced transmembrane Ca2+ flux. Taken together, these data are consistent with the hypothesis that ET-1-induced vasoconstriction may play an important modulatory role in the vascular compromise characteristic of T. cruzi infection.

Animals↗

Influence of early posttraumatic hypothermia therapy on local cerebral blood flow and glucose metabolism after fluid-percussion brain injury.

OBJECT: Using autoradiographic image averaging, the authors recently described prominent foci of marked glucose metabolism-greater-than-blood-flow uncoupling in the acutely traumatized rat brain. Because hypothermia is known to ameliorate injury in this and other injury models, the authors designed the present study to assess the effects of posttraumatic therapeutic hypothermia on the local cerebral metabolic rate of glucose (LCMRglu) and local cerebral blood flow (LCBF) following moderate parasagittal fluid-percussion head injury (FPI) in rats. METHODS: Either cranial hypothermia (30 degrees C) or normothermia (37 degrees C) was induced for 3 hours in matched groups of rats immediately after FPI; LCMRglu and LCBF were assessed 3 hours after concluding these temperature manipulations. In rats subjected to FPI, regardless of whether normothermia or hypothermia ensued, LCBF was reduced relative to the sham-injury groups. In addition, when FPI was followed by hypothermia (FPI-30 degrees C group), the subsequent LCBF was significantly lower (35-38% on average) than in FPI-37 degrees C rats. Statistical mapping of LCBF difference imaging data revealed confluent cortical and subcortical zones of significantly reduced LCBF (largely ipsilateral to the prior injury) in FPI-30 degrees C rats relative to the FPI-37 degrees C group. Local glucose utilization was reduced in both hemispheres of FPI-37 degrees C rats relative to the sham-injury group and was lower in the right (traumatized) hemisphere than in the left. However, LCMRglu values were largely unaffected by temperature manipulation in either the FPI or sham-injury groups. The LCMRglu/LCBF ratio was nearly doubled in FPI-30 degrees C rats relative to the FPI-37 degrees C group, in a diffuse and bihemispheric fashion. Linear regression analysis comparing LCMRglu and LCBF revealed that the FPI-37 degrees C and FPI-30 degrees C data sets were completely nonoverlapping, whereas the two sham-injury data sets were intermixed. CONCLUSIONS: Despite its proven neuroprotective efficacy, early posttraumatic hypothermia (30 degrees C for 3 hours) nonetheless induces a moderate decline in cerebral perfusion without the (anticipated) improvement in cerebral glucose utilization, so that a state of mild metabolism-greater-than-blood-flow dissociation is perpetuated.

Animals↗

Irradiation of rat mesangial cells alters the expression of gene products associated with the development of renal fibrosis.

To determine the ability of radiation to modulate mesangial cell expression of various molecules involved in promoting extracellular matrix (ECM) accumulation [fibronectin, plasminogen activator-inhibitor 1 (Pai1), and tissue inhibitor of metalloproteinase-2 (Timp2)] and degradation (Tgfb, plasminogen activators u-PA or t-PA, matrix metalloproteinases Mmp2 and Mmp9), primary cultures of rat mesangial cells (passage number 6-11) were placed in serum-free medium 24 h prior to irradiation with single doses of 0.5-20 Gy (137)Cs gamma rays. After irradiation, cells were maintained in serum-free medium for a further 48 h. Irradiation of quiescent mesangial cells resulted in significant (P < 0.05) time- and dose-dependent increases in Fn and Pai1 mRNA and/or immunoreactive protein. Despite an increase in Tgfb1 mRNA, there was little evidence for an increase in total Tgfb protein. Indeed, active levels remained unaltered after irradiation. Irradiation led to differential changes in MMP expression; active Mmp2 levels increased, while Mmp9 levels appeared unaltered. In addition, secretion of plasminogen activators into the medium was unchanged after irradiation, while secretion of Timp2 increased. We conclude that irradiating mesangial cells leads to altered production of various molecules involved in accumulation and degradation of extracellular matrix.

Animals↗

Radiation-induced alterations in rat mesangial cell Tgfb1 and Tgfb3 gene expression are not associated with altered secretion of active Tgfb isoforms.

Despite evidence of selective radiation-induced modulation of expression of rat mesangial cell Tgfb gene isoforms, it is unclear whether these changes in gene expression are accompanied by changes in protein secretion. To address this issue, primary cultures of rat mesangial cells (passage number 6- 11) were placed in serum-free medium 24 h prior to irradiation with single doses of 0.5-20 Gy of (137)Cs gamma rays. After irradiation, cells were maintained in serum-free medium for a further 24 h. Irradiation of quiescent mesangial cells resulted in a significant (P </= 0.05) dose-independent increase in steady-state levels of Tgfb1 mRNA 24 h postirradiation. In contrast, steady-state levels of Tgfb3 mRNA exhibited a dose-dependent reduction after irradiation; this reduction was statistically significant after doses of 5 and 10 Gy compared to control cells (P </= 0.05). These radiation-induced changes in Tgfb gene expression were associated with modest increases in Tgfb protein as determined using mink lung epithelial cells transfected with the Pai1 promoter-luciferase construct. Twenty-four hours after a single dose of 5 Gy, the total Tgfb protein secreted by the mesangial cells was 181 +/- 2.0% of that secreted by unirradiated control cells (P </= 0.01). However, this increase was seen in terms of latent Tgfb protein; radiation failed to increase significantly the amount of active Tgfb protein secreted by mesangial cells. Both quiescent and irradiated rat mesangial cells secreted active Tgfb as primarily the Tgfb3 isoform. These data reinforce the need to interpret changes in Tgfb gene expression with caution.

Animals↗

[Seroepidemiological study on Helicobactor pylori infection in rural adult residents].

OBJECTIVE: To study the prevalence of Helicobactor pylori (Hp) infection in rural adult residents of China and its relation to serum levels of pepsinogen I (PG I), pepsinogen II (PG II) and gastrin (GAS). METHODS: Serum levels of antibodies against Hp were determined with enzyme-liked immunosorbent assay (ELISA) in 1,504 residents aged over 30 in Zanhuang County of Hebei Province, and their serum levels of PG I, PG II and GAS, as well as PG I/PG II ratio, were analyzed quantitatively, with radioimmunoassay (RIA). RESULTS: Positivity for serum Hp antibody accounted for 66.4% of the rural adults in Zanhuang County, without significant sex difference. There was no significant difference in positivity for serum Hp antibody between residents in the high and low prevalent areas of gastric cancer. Serum levels of PG I, PG II and GAS were significantly higher in those with positive serum IgG anti-Hp (62.3 micrograms/L, 15.45 micrograms/L and 74.00 pg/ml, respectively) than those negative (42.1 micrograms/L, 6.40 micrograms/L and 66.00 pg/ml, respectively), all with a P-value less than 0.005, and the ratio of serum PG I to PG II levels was significantly lower in the former (4.0) than that in the latter (6.6), with P < 0.005. CONCLUSION: More than two thirds of the adult residents in Zanhuang County had infected with Hp, which could affect their serum levels of PG and GAS.

Adult↗

Ion Channels and Gap Junctions: Their Role in Erectile Physiology, Dysfunction, and Future Therapy.

A flurry of research and clinical activity during this past decade has documented that the tonicity and synchronicity of the corporal smooth muscle cells of the penis are major determinants of erectile capacity and function. Specifically, the effects of diverse and bifurcating intracellular signal transduction pathways on the activity of nonjunctional ion channels such as potassium (K(+)), calcium (Ca(2+)), and chloride (C(1-)) govern the former, whereas intercellular communication through gap junctions provides the anatomic substrate for the latter. Recent studies at the tissue, cellular, subcellular, and molecular levels have verified this supposition and provided important insight into how subtle alterations in the balance between contraction and relaxation of the corporal smooth muscle cells can predispose a man to erectile failure. This report reviews the available information concerning the participation of gap junctions and K(+), Ca(2+), and C(1-) channels in the erectile process and describes their importance as potential molecular targets for the future therapy of erectile dysfunction (ED). It is argued that a major goal should now be to proceed on at least two fronts simultaneously: (1) to capitalize on these new mechanistic insights by developing novel treatments for ED centered on the modulation of ion channel activity; and (2) simultaneously to take advantage of the unique therapeutic opportunities afforded by the presence and ubiquitous distribution of gap junction channels in the human corpora. One strategy that fulfils both criteria will be briefly reviewed, that is, gene therapy with the maxi-K(+) channel subtype.

Journal Article↗

[Determination of plasma serotonins level in patients with pregnancy induced hypertension].

OBJECTIVE: To determine whether levels of serotonin(5-HT) and 5-hydroxy-indolescetic acid (5-HIAA) play an important role in the pathogenesis of pregnancy induced hypertension (PIH). METHODS: Maternal venous blood were collected from 60 women with PIH and 40 normotensive pregnant women in third trimester as control, and umbilical venous blood were collected from 38 newborns in each groups. Plasma and platelet 5-HT and 5-HIAA levels were measured by spectrophotometry. RESULTS: The mean 5-HT level was (54.16 +/- 10.13) nmol/L and 5-HIAA was (43.62 +/- 6.37) nmol/L in maternal plasma, while they were (50.23 +/- 7.83) nmol/L and (41.73 +/- 8.61) nmol/L in umbilical plasma respectively in the normotensive group. The mean 5-HT was (86.24 +/- 14.37) nmol/L and 5-HIAA was (62.37 +/- 8.34) nmol/L in maternal plasma of patients with PIH. While the mean 5-HT was (71.56 +/- 10.13) nmol/L and 5-HIAA was (62.37 +/- 11.37) nmol/L in umbilical plasma in PIH group. 5-HT and 5-HIAA levels in maternal and umbilical blood of PIH groups were significantly higher than that in the control group (P < 0.01). CONCLUSIONS: The markedly elevated plasma 5-HT and 5-HIAA levels might be caused by the increased release of 5-HT by platelet. The result showed that elevated levels of 5-HT and 5-HIAA in patients with PIH might take part in the pathogenesis of PIH.

Adult↗

[Detection of antineutrophil cytoplasmic autoantibodies in pregnancy induced hypertension and its clinical significance].

OBJECTIVE: To explore the level of antineutrophil cytoplasmic autoantibodies (ANCA) in patients with pregnancy induced hypertension (PIH) and its clinical significance. METHOD: 37 cases with PIH and 39 non-PIH pregnancy were studied for ANCA by indirect immunflourscence. RESULTS: ANCA positive rates were 33.3%, 88.9% and 86.4% in mild, moderate, severe PIH, respectively, and most of them were c-ANCA. The positive rate was only 13.2% in non-PIH control, significantly lower than those in PIH (P < 0.001). CONCLUSION: ANCA may be one of the causes for endothelial cell damage and a predicting marker in PIH.

Adult↗

[Effect of Baoyuan Qiangshen capsule no. II on tubular interstitial injury in chronic renal failure patients].

OBJECTIVE: To investigate the protective effect and mechanism of Baoyuan Qiangshen Capsule No. II (BYQS) in treating chronic renal failure (CRF). METHODS: Sixty patients of CRF were divided into 2 groups randomly, the tested group treated with BYQS combined with Lotensin and the control group treated with essential amino acid combined with Lotensin. Changes of renal function and tubular marked proteins were observed. RESULTS: The markedly effective rate and total effective rate of the tested group were 63.3% and 93.3% respectively and those of the control group were 30.0% and 56.7% respectively, the effect of the tested group was markedly better than that of the control group (P < 0.01). In the tested group after treatment, BUN, SCr and CCr were improved significantly, urine retinol binding protein and beta 2-microglobulin and N-acetyl-beta-D-glucosamindase decreased significantly (P < 0.01), while Tamm-Horfau protein increased significantly (P < 0.05). CONCLUSION: BYQS could alleviate tubular interstitial injury significantly so as to improve the renal function and enhance the effective rate in treating CRF.

Adolescent↗

[Clinical and experimental study on treatment of Helicobacter pylori infected gastritis by xialian yiyou capsule].

OBJECTIVE: To observe the therapeutic effect of Xialian Yiyou Capsule (XLYYC) on helicobacter pylori (HP) infected gastritis to develop the serial Chinese classical recipe. METHODS: HP infected patients were divided into two groups, 136 patients in the XLYYC group treated with XLYYC and 90 patients in the control group treated with Lizhu Dele Capsule, for 4 weeks as one therapeutic course, the clinical therapeutic effect was observed, and corresponding animal experiments were done. RESULTS: Clinical effect of the XLYYC group was better than that of the control group in improving clinical symptoms, relieving inflammation of gastric mucosa and eliminating HP (P < 0.05, P < 0.01). Results of animal experiment showed that XLYYC was superior than the control significantly in anti-inflammation, analgesia, stomach emptying and curing gastric ulcer model (P < 0.05, P < 0.01). Without any adverse reaction has been found in acute toxicologic study. CONCLUSION: The therapeutic effect of XLYYC in treating HP infected gastritis was definite and safe, non-toxic.

Adolescent↗

[Extensive transbasal approach for removal of tumours in the nasal, sphenoid and clival regions].

OBJECTIVE: To improve operative results of removal of the tumors in midline cranial base and the reconstruction of defect at frontal base through modification of the operative approach and techniques. METHODS: Extensive transbasal approach was used in 15 patients with tumours in the nasal, sphenoid and clival regions. RESULTS: The tumor was removed in 10 patients, near totally removed in 4 and partial removed in 1. The operative results of all patients were excellent except an elderly patient with mild operative morbidity. CONCLUSIONS: The procedure we used expand the operative indications for the tumors situated at the midline cranial base and improve the operative results. The procedure has advantages such as wide operative space, reliable reconstruction of the frontal base, and no severe complications.

Adult↗

[Study on the antidiuretic efficacy and mechanism of indapamide in central diabetes insipidus].

OBJECTIVE: To investigate the efficacy and antidiuretic mechanism of indapamide in central diabetes insipidus. METHODS: We observed eight patients with central diabetes insipidus treated by indapamide (2.5-7.5 mg.d-1) or dihydro-chlorothiazide (50-70 mg.d-1) or carbamazepine (150-300 mg.d-1) for 8 days with randomized block design. The therapy was changed twice in sequence after 4 days without treatment. Urine output and indexes of water metabolism were also observed. RESULTS: The urine output was reduced on the 4th day and 8th day with each therapy. The serum potassium and chloride concentration was decreased and renin activity was increased on the 4th and 8th day with indapamide therapy. CONCLUSION: Indapamide has antidiuretic action on central diabetes insipidus. The action may result from the changes of hydroelectrolytes and renin-angiotensin-aldosterone system.

Adolescent↗

[A study on major chemical components of Uvaria grandiflora].

OBJECTIVE: To make clear the chemical constituents of Uvaria grandiflora (Annonaceae). METHODS: Purification was performed using sephadex LH-20 permeation and silica gel chromatography. Structures of the purified components were determined on the basis of 1H, 13C NMR analysis and also by comparison with those of authentic compounds. RESULTS: Two major triterpenes, suberosol and lupeol, were identified. CONCLUSION: This paper is the first report on the identification of suberosol and lupeol from the gunus Uvaria.

Pentacyclic Triterpenes↗

Suppressive effect of carotenoids on the luminol dependent chemiluminescence of the stimulated rat macrophages.

Rat macrophages stimulated by phorbol 12-myristate 13-acetate (PMA) produced significant chemiluminescence in luminol. Carotenoids suppressed the luminol-dependent chemiluminescence at the beginning and after two minutes of the stimulation. Canthaxanthin and bixin had higher suppressive activity that beta-carotene and lutein. The measurement of the absorption spectra of carotenoids showed that the absorption by carotenoids was diminished during the stimulation of macrophages. The results suggest that the suppressive effect of carotenoids may be due to their scavenging the reactive oxygen metabolites released by macrophages.

Animals↗

Pixel-based image analysis of HSP70, GADD45 and MAP2 mRNA expression after focal cerebral ischemia: hemodynamic and histological correlates.

Gene expression studies with in situ hybridization after focal brain ischemia indicate a variety of distinct anatomical patterns. An important question is to what extent such reactive gene expression correlates with neuronal damage or survival. To study these questions, we focused on two stressed-induced genes, heat shock protein 70 (HSP70) and growth-arrest and DNA damage-inducible gene (GADD) 45 mRNA, and we compared reactive changes in mRNA to loss of the constitutive signal for microtubule-associated protein 2 (MAP2) mRNA. A pixel-based image analysis of mRNA signals was carried out using a highly reproducible model of focal brain ischemia. A poly-l-lysine coated filament was used to occlude the origin of the middle cerebral artery (MCA) for 2 h in ventilated, normothermic rats. Brains were collected after 0, 1, 3 and 6 h, and 1, 3 and 7 days. In situ hybridization analysis was carried out for HSP70 mRNA, GADD45 mRNA and MAP2 mRNA. Autoradiographic data sets were averaged and co-mapped into a common template of the rat brain. These data sets were then compared on a pixel-by-pixel basis with previously acquired image data sets derived from quantitative studies of local cerebral blood flow (LCBF) (obtained at the end of 2-h ischemia) of and infarctive histopathology (obtained at 3 days) in the same focal ischemia model. HSP70 mRNA and GADD45 mRNA were grossly elevated in the hemisphere subjected to ischemia during the first day. Pixel-based analysis showed a strong correlation between HSP70 mRNA signals, the degree of early blood-flow reduction and the probability of histological infarction. GADD45 mRNA was expressed in a more variable fashion. Decreases in MAP2 mRNA signals at 1, 3 and 7 days correlated strongly with histological infarction. These co-mapping procedures allow us to conclude that HSP70 mRNA is a robust indicator of ischemic stress and histological outcome after 2 h of focal brain ischemia. The topographic features of GADD45 expression suggest its possible role in conferring resistance to ischemic injury. Finally, our results indicate that local decreases in constitutive MAP2 expression at 1 day and beyond may be used as a robust marker of tissue regions having a high probability of focal infarction.

Animals↗