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Biomedical subjects

P Yu

Publications and source records attributed to P Yu.

At least 55 records · Page 3Linked to original sources
PubMed2001

Effects of microinjection of melatonin and its receptor antagonists into anterior hypothalamic area on blood pressure and heart rate in rats.

AIM: To examine the effects of microinjection of melatonin and its receptor antagonists into the anterior hypothalamic area (AHA) on blood pressure (BP) and heart rate (HR) in normotensive and stress-induced hypertensive rats. METHODS: Melatonin and its receptor antagonists were microinjected into the AHA, then BP, mean arterial pressure (MAP), and HR were synchronously recorded. RESULTS: Microinjection of melatonin produced a fall in MAP. Prazosin, an antagonist of melatonin ML2 receptor, could not antagonize the depressive response induced by melatonin. While luzindole, a competitive antagonist of melatonin ML1 receptor, was able to almost completely prevented the depressive response induced by injection of melatonin. CONCLUSION: Melatonin acts as a hypotensive factor and the effects are mainly due to activation of ML1 receptors in rat brain, and the AHA may be one of the important central areas where melatonin can exert modulatory effects on BP and HR.

Animals↗
PubMed2001

Modelling viral and CD4 cellular population dynamics in HIV: approaches to evaluate intervention strategies.

Computational models, such as in epidemiology, provide a powerful tool that can be used to systematically examine an array of dynamic interactions among populations as well as to evaluate altemate disease intervention strategies. The specific objectives in this study were to: a/ examine the interaction of cellular (CD4) and HIV population dynamics and evaluate the impact of the use of combination chemotherapies on viral and CD4 populations (Experiment #1), b/ demonstrate how modelling can be used to evaluate the impact of an intervention (condom use) on reducing the rate of HIV/AIDS (Experiment #2). In this study, we used state transition models and conducted simulation experiments to evaluate various alternatives for the control and/or prevention of HIV/AIDS. The result indicated that combination therapy (double or triple drug therapies) was very effective. The HIV viral population decreased rapidly and remained suppressed for years. On the other hand, the CD4 cell population increased above 400 cells per ml and was maintained above that level for many years. Mono-therapy was not as effective; although the viral load decreased rapidly, it increased to its original levels within a few months. Since condom use is one of the key interventions of HIV/AIDS, we evaluated its use in 25%, 50% and 75% of an adult, sexually active population. Increasing condom use by 50% and 75% above an estimated baseline of 25% reduced the incidence of AIDS by 53% in Blacks, 49% in Hispanics and 43% in Whites. The study shows how a cellular/molecular level model can be incorporated within a macro-epidemiologic systems dynamics model to evaluate a variety of scientific questions such as to see if cellular/molecular level interventions reduce morbidity and mortality rates in HIV.

Anti-HIV Agents↗
PubMed2001

[A survey of the current status and distribution of cataract in the elderly].

OBJECTIVE: To study the current status and distribution of cataract in the ageing population. METHODS: A total number of 8,252 elderly aged 60 years and above in the urban and rural areas of Beijing, Shanghai, Guangzhou, Chengdu, Xi'an and Shenyang were studied, using cluster random sampling methods. RESULTS: The crude and adjusted rates of cataract prevalence in the elderly were found to be 46.8% and 42.8% respectively. However, the self-reported crude prevalence was 19.7% with only 42.1% of that shown by medical examination. The prevalence rates increased with ageing (P < 0.01), to have shown 27.9%, 41.3%, 53.2%, 67.5% and 68.0% in the age groups of 60-, 65-, 70-, 75-, 80-, 85- years old respectively (P < 0.01). There was difference in the prevalence among areas, with highest (77.9%) in the urban areas in Guangzhou and in the rural areas in Beijing (67.3%) (P < 0.01). The prevalence differed in gender as well: higher in women (49.1%, adjusted) than in men (35.6%, adjusted). Logistic regression analysis showed that the crude prevalence was correlated with ageing, profession and area (P respective < 0.01). CONCLUSION: The prevalence of cataract was high in the elderly and increased with ageing with differences in areas, and professions. It was low when self-reporting shown by medical examination, suggesting prevention and treatment of cataract in the elderly be strengthened.

Age Factors↗
PubMed2001

[Current status and distribution of deafness in the elderly in several cities in China].

OBJECTIVE: To survey the current status and distribution of deafness and its effect on daily life activities in the old population. METHODS: Eight thousand two hundred and fifty-two elderly aged 60 years and above in the urban and rural areas of Beijing, Shanghai, Guangzhou, Chengdu, Xi'an and Shenyang were investigated, using a clustered random sampling methods. RESULTS: Overall crude prevalence of deafness in the elderly was found to be 33.7%, but the self-reported crude prevalence was low, only 47.1% when shown by medical examination. Crude prevalence rates were increasing with ageing, with 21.6%, 30.0%, 35.6%, 42.6%, 55.5% and 61.6% respectively (P < 0.01) in the age groups of 60-, 65-, 70-, 75-, 80-, 85- years old. Rate of deafness was highest in Beijing (58.5%), among the in-house workers (48.9%) and the lowest in scientists, teacher and health workers (28.5%). Logistic regression analysis showed that the crude prevalence was related to ageing, profession and area (P respective < 0.01). CONCLUSION: The prevalence of deafness was high in the elderly which increased with ageing with different areas, professions and the level of education. It was lower when self-reported than shown by medical examination. Prevention and treatment of deafness in the elderly should be strengthened.

Age Factors↗
PubMed2001

[Study on effect of Astragalus injection in treating congestive heart failure].

OBJECTIVE: To observe the clinical efficacy and side-effects of Astragalus Injection (AI) in treating congestive heart failure (CHF). METHODS: Eighty-three patients of CHF with heart function of II-IV grade assessed by NYHA (New York Heart Association) classification were randomly divided into 2 groups. The 42 patients in the treated group were treated with AI 40 ml (equivalent to 80 g crude drug) by adding in 5% glucose solution 500 ml for intravenous dripping, once a day and the 41 patients in the control group were treated by nitrolingual injection 15 mg by adding in 5% glucose solution 500 ml for intravenous dripping once a day. The therapeutic course in both groups was 2 weeks and the patients were followed-up for 1-6 months. RESULTS: The clinical heart function improvement rate and the total effective rate in the treated group after 1 month treatment were 26.2% and 78.6%, and after 6 months were 34.2% and 81.6% respectively, which were superior to those in the control group significantly (P < 0.05 or P < 0.01). The levels of left ventricular ejection fraction (LVEF), fractional shortening of left ventricular short axis (FS), the ratio of maximum blood flow between the advanced and early atrial systole (E/A), stroke volume (SV), cardiac output (CO) and the cardiac index (CI) were all improved in both groups (P < 0.01 or P < 0.05), but better improvement was shown in the treated group. Follow-up study showed that the incidence of cardiac event was lower in the treated group than that in the control group (P < 0.05). CONCLUSION: AI can be took as one of the important auxiliary drugs for treatment of CHF especially in severe cases.

Aged↗
PubMed2000

[Candida albicans resistance and genotyping by randomly amplified polymorphic DNA method].

The Etest was used to determine the minimum inhibitory concentrations(MICs) of five antifungal agents for 30 C. albicans clinical isolates. Randomly amplified polymorphic DNA(RAPD) analysis was established and was used to type 30 epidemiological unrelated strains of C. albicans. The relationship between genotype of C. albicans and its resistance to antifungal was analysed by dendrogram according to RAPD patterns. The results were that there were 2 of 30 isolates of C. albicans against fluconazole and their RAPD profiles had high similarity. These results suggest that a high degree of genetic correlation exists between fluconazole-resistant patterns and RAPD profiles of C. albicans.

Antifungal Agents↗
PubMed2000

Enantiospecific total synthesis of the sarpagine related indole alkaloids talpinine and talcarpine as well as the improved total synthesis of alstonerine and anhydromacrosalhine-methine via the asymmetric Pictet-Spengler reaction.

The enantiospecific total synthesis of talpinine 1 and talcarpine 2 has been accomplished from D-(+)-tryptophan in 13 steps (11 reaction vessels) in 10% and 9.5% overall yields, respectively. Moreover, this synthetic approach has been employed for the improved synthesis of alstonerine 3and anhydromacrosalhine-methine 4 in 12% and 14% overall yield, respectively. A convenient synthetic route for the enantiospecific, stereospecific preparation of the key intermediate (-)-N(a)-H, N(b)-benzyl tetracyclic ketone 15a via the asymmetric Pictet-Spengler reaction on a multihundred-gram scale has been developed. A diastereocontrolled (>30:1) anionic oxy-Cope rearrangement and the intramolecular rearrangement to form ring-E and an N(b)-benzyl/N(b)-methyl transfer reaction also served as key steps. This general approach can now be utilized for the synthesis of macroline/sarpagine related indole alkaloids and their antipodes for biological screening.

Alkaloids↗
PubMed2000

Alzheimer's disease: transgenic mouse models and drug assessment.

Alzheimer's disease (AD), characterized by neuritic plaques and neurofibrillary tangles of the brain, is experienced by more and more elderly people in a form of senile dementia. Four genes are closely linked with AD and are located on chromosomes 21, 19, 14 and 1. Transgenic technology enables the development of animal models for research into this human disease. Recently reported transgenic AD mouse models, which express AD-related mutant human genes, develop some significant aspects of AD-like pathology. The specific role of these mice in representing different targets, the consequent pathology of AD and the availability of this increasingly popular tool for investigating new therapeutic strategies for AD are reviewed.

Alzheimer Disease↗
PubMed2000

An independently addressable microbiosensor array: what are the limits of sensing element density?

A microdisc sensor array, prepared by thin film technology, has been used as a model for miniaturized multi-functional biosensors. It consists of a series of wells, 20 microns in diameter, possessing a 1000 A Pt layer at the bottom that serves as the indicating electrode. The depth of the wells ranged from 2.3-24 microns, depending on the photoresist employed and the spinning speed used to coat the electrode interconnect grid. Ten such wells were arranged in a circular array within an area of radius 130 microns. The center to center distance between any two of the discs ranged from 30 to 155 microns. Each disc is connected by a conductive film line to corresponding pads on the side of the sensor chip. A cylinder placed on top of the chip array formed the electrochemical cell into which a common reference and counter electrode were placed. The reference electrode was operated at ground potential. Prior to the evaluation of enzyme sensors, an assessment of "chemical cross-talk", the perturbation of sensor response resulting from the overlap of proximal diffusion layers, was made using Fe(CN)6(4-). The preliminary conclusion is that the sensing elements probably must be separated by about 100 microns in order to avoid interference from adjacent sensors. A technique was developed for the precision delivery of enzyme and cross-linking agent to the 2.3 microns cavity, having a capacity of 4 pL. This procedure makes possible the preparation of sensor arrays capable of detecting different analytes by employing different enzymes. The sensors gave reasonably rapid (2-4 s) response with linearity (up to about 10 mM. However, the sensors in the center of the array clearly showed the effects of depletion of substrates by the surrounding sensors.

Biosensing Techniques↗
PubMed2000

Increased gut permeability and bacterial translocation in Pseudomonas pneumonia-induced sepsis.

OBJECTIVE: Gut injury and barrier dysfunction may contribute to the pathogenesis of sepsis and multiple organ dysfunction syndrome. The objective of this study was to determine whether gut injury could be demonstrated in hyperdynamic, normotensive sepsis induced by Pseudomonas pneumonia. DESIGN: Randomized animal study. SETTING: University laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Sepsis was induced by intratracheal instillation of Pseudomonas aeruginosa. MEASUREMENTS AND MAIN RESULTS: We measured gut mucosal and microvascular injury. In the first experiment, gut mucosal permeability was measured by 51Cr-EDTA uptake in control (n = 6), pneumonia 20-hr (n = 4), and pneumonia 40-hr (n = 4) groups. In the second experiment, microvascular permeability was measured by albumin extravasation, and morphologic abnormalities were scored in control (n = 6), pneumonia 20-hr (n = 9), and pneumonia 40-hr (n = 11) groups. Bacterial translocation to mesenteric lymph nodes was determined in both experiments. Cardiac index increased significantly in the pneumonia compared with control rats (64+/-2.1, 68+/-1.3, vs. 46+/-2 mL/min/100 g, p < .05; all results are listed in the order of pneumonia 20-hr, pneumonia 40-hr, and control groups as mean +/- SEM). Mean blood pressure was normal and was not different between groups (112+/-3, 111+/-2, vs. 118+/-2 mm Hg). 51Cr-EDTA recovery in urine 6 hrs after gavage increased significantly in both pneumonia groups vs. controls (17.5+/-2.2%, 17.9+/-7%, vs. 4+/-0.7%; p < .05). Albumin leak (tissue/plasma ratio) increased significantly in the middle and distal small intestine in the pneumonia 40-hr group vs. controls (0.68+/-0.05, 0.76+/-0.07, vs. 0.45+/-0.04, p < .05 in the middle small gut; 0.75+/-0.09, 0.85+/-0.07, vs. 0.51+/-0.05, p < .05 in the distal small gut). Bacterial translocation to mesenteric lymph nodes increased significantly in pneumonia 40-hr rats vs. controls (positive culture 67% vs. 8%; p < .05). CONCLUSIONS: This study demonstrates gut mucosal and microvascular injury and gut barrier dysfunction in normotensive sepsis secondary to bacterial pneumonia. The mechanism and significance of the injury need to be determined.

Animals↗
PubMed2000

Effects of physiologic albumin and hespan levels on hepatocytes in vitro.

BACKGROUND: Although albumin and hydroxyethyl starch (HES) are routinely used in critically ill, hypoalbuminemic patients, no studies have tested the effect of supplemental albumin and HES on hepatocyte function. METHODS: In this study, the effects of these agents were evaluated by using stable, rat hepatocyte cultures in a collagen sandwich configuration. Hepatocyte synthesis of albumin, urea, and intracellular triglycerides was monitored in Dulbecco's modified Eagle medium (supplemented with fetal bovine serum, hydrocortisone, L-proline, gentamycin, and insulin) without supplemental colloid (control cultures) and with supplemental 2% bovine serum albumin (BSA), 4% BSA, 2% HES, or 4% HES. RESULTS: The albumin secretion in control cultures rose from 31.03 microg/day per 10(6) cells on day 3 to 154.17 microg/day per 10(6) cells by day 12 and remained constant. In contrast, the level of albumin synthesis in the 2% and 4% BSA groups rose from significantly higher initial values (p < 0.05) of 71.25 microg/day per 10(6) cells and 73.27 microg/day per 10(6) cells, respectively, to 127.61 microg/day per 10(6) cells and 107.95 microg/day per 10(6) cells by day 7, then declined rapidly to 58.98 microg/day per 10(6) cells and 41.28 microg/day per 10(6) cells by day 12 when cell disruption was present. HES also reduced albumin synthesis. The urea genesis in the control groups and in the treatment groups was found to be comparable throughout the study. The BSA supplemented groups accumulated large amounts of intracellular lipid droplets during the experiment. The intracellular triglycerides analysis found the 4% BSA group to be significantly (p < 0.05) higher than the 4% HES. CONCLUSION: BSA, added to a collagen sandwich hepatocyte preparation, causes reduced hepatocyte synthesis by day 8, probably a result of intracellular triglyceride accumulation, whereas HES reduces synthesis through unidentified mechanisms.

Albumins↗
PubMed2000

Osteogenesis in cranial defects: reassessment of the concept of critical size and the expression of TGF-beta isoforms.

Transforming growth factor-betas (TGF-beta) have been demontstrated to be upregulated during osteoblast function in vitro and during cranial suture fusion in vivo. The authors hypothesized that spontaneous reossification of calvarial defects was also associated with upregulation of TGF-beta. The present study was designed to (1) evaluate the concept of a critical-size defect within the calvaria in an adult guinea pig model and (2) investigate the association between the ossification of calvarial defects and TGF-beta upregulation. Paired circular parietal defects with diameters of 3 and 5 mm and single parietal defects with diameters of 8 or 12 mm were made in 45 six-month-old skeletally mature guinea pigs. Three animals per defect size were killed after survival periods of 3 days, 1 week, 4 weeks, 8 weeks, or 12 weeks. New bone ingrowth was evaluated by assessing for linear closure by a traditional linear method and by a modified cross-sectional area method using an image analysis system in which the thickness of new bone was taken into account. Immunohistochemistry was performed using rabbit polyclonal antibodies to localize TGF-beta1, -beta2, and -beta3. All specimens were photographed, and the intensity of immunostaining was graded based on subjective photographic assessment by three independent reviewers. No defect demonstrated any measurable bone replacement after a survival period of 3 days. All 3- and 5-mm defects were completely reossified after 12 weeks based on the linear analysis of new bone, indicating these defects to be less than critical size. However, new bone formation in the 5-mm defects never exceeded a mean of 40 percent by cross-sectional area of new bone. Percent of new bone formation by cross-sectional area was significantly higher within 3-mm defects than in all larger defects 4 weeks after the craniotomy, reaching a mean of 89 percent new bone by 12 weeks. Persistent gaps were noted on linear analysis of the 8- and 12-mm wounds by 12 weeks, and mean percent new bone by cross-sectional area remained below 30 percent. Immunolocalization demonstrated osteogenic fronts at the advancing bone edge and the endocranial side, in which the osteoblasts stained strongly for all isoforms of TGF-beta. The intensity of osteoblast expression waned considerably after the majority of the defect had reossified. These data indicate that histometric analysis based on cross-sectional area more accurately reflects the osteogenic potential of a cranial defect than does linear inspection of defect closure. Although the interpretation of immunolocalization studies is highly subjective, independent assessment by three reviewers indicates that isoforms of TGF-beta were upregulated during a limited "window" of time corresponding to the period of active calvarial reossification, and expression of TGF-beta corresponded to osteoblast activity within osteogenic fronts.

Animals↗
PubMed2000

An alternative thermodilution method to measure cardiac output in a rat model of stagnant hypoxia.

Rats are often used to study hemodynamics in animal research. We have established an alternative method to measure cardiac output in a conscious rat using a thermodilution technique via a left ventricular injection. The validity of this method was evaluated in conscious rats and compared with the results obtained using the radiolabeled microspheres (reference sample method). Using 20 male Sprague-Dawley rats, a baseline cardiac index was measured by thermodilution to determine the baseline cardiac index and to evaluate between animal variability. The baseline cardiac index was compared to the reference sample method with 6 rats. Following baseline measurements, an intra-atrial balloon was inflated in a stepwise manner to create 2 to 3 different cardiac outputs, and the cardiac index was computed. For each measurement, the cardiac index was first measured by thermodilution and immediately followed by the reference sample method. A total of 21 measurements were obtained, and the results were analyzed by a Bland-Altman plot and the correlation coefficient was calculated. Although the agreement between the two methods was poor, both methods had a good correlation (r2 = 0.59). With the thermodilution technique, we demonstrated a small coefficient of variation in each measurement, with a low intra-animal and inter-animal variability. As there is no gold standard method to measure cardiac output in rats, we believe that left ventricular thermodilution is a reliable method, and overcomes several technical difficulties such as heat loss, one of the significant limitations of the conventional thermodilution method (via right atrial injection). This new thermodilution technique (via the left ventricle) is therefore an attractive alternative method to measure cardiac output in rats.

Animals↗
PubMed2000

Diaspirin cross-linked Hb and norepinephrine prevent the sepsis-induced increase in critical O(2) delivery.

We hypothesized that support of arterial perfusion pressure with diaspirin cross-linked Hb (DCLHb) would prevent the sepsis-induced attenuation in the systemic O(2) delivery-O(2) uptake relationship. Awake septic rats were treated with a chronic infusion of DCLHb or a reference treatment [norepinephrine (NE)] to increase mean arterial pressure by 10-20% over 18 h. Septic and sham control groups received normal saline. Isovolemic hemodilution to create anemic hypoxia was then performed in a metabolic box during continuous measurement of systemic O(2) uptake. O(2) delivery was calculated from hemodynamic variables, and the critical point of O(2) delivery (DO(2 crit)) was determined using piecewise regression analysis of the O(2) delivery-O(2) uptake relationship. Sepsis increased DO(2 crit) from 4.99 +/- 0.17 to 6.69 +/- 0.42 ml x min(-1) x 100 g(-1) (P < 0.01), while O(2) extraction capacity was decreased (P < 0.05). DCLHb and NE infusion prevented the sepsis-induced increase in DO(2 crit) [4.56 +/- 0.42 ml x min(-1) x 100 g(-1) (P < 0.01) and 5.04 +/- 0.56 ml x min(-1) x 100 g(-1) (P < 0.05), respectively]. This was explained by a 59% increase in O(2) extraction capacity in the DCLHb group compared with septic controls (P < 0.05), whereas NE treatment decreased systemic O(2) uptake in anemic hypoxia (1.51 +/- 0.08 vs. 1.87 +/- 0.1 ml x min(-1) x 100 g(-1) in septic controls, P < 0.05). We conclude that DCLHb ameliorated O(2) extraction capacity in the septic microcirculation, whereas NE decreased the metabolic demands of the tissues.

Animals↗
PubMed2000

Renal protein phosphatase 2A activity and spontaneous hypertension in rats.

The impaired renal paracrine function of dopamine in spontaneously hypertensive rats (SHR) is caused by hyperphosphorylation and desensitization of the renal D(1) dopamine receptor. Protein phosphatase 2A (PP(2A)) is critical in the regulation of G-protein-coupled receptor function. To determine whether PP(2A) expression and activity in the kidney are differentially regulated in genetic hypertension, we examined the effects of a D(1)-like agonist, fenoldopam, in renal cortical tubules and immortalized renal proximal tubule cells from normotensive Wistar-Kyoto rats (WKY) and SHR. In cortical tubules and immortalized proximal tubule cells, PP(2A) expression and activities were greater in cytosol than in membrane fractions in both WKY and SHR. Although PP(2A) expressions were similar in WKY and SHR, basal PP(2A) activity was greater in immortalized proximal tubule cells of SHR than WKY. In immortalized proximal tubule cells of WKY, fenoldopam increased membrane PP(2A) activity and expression of the regulatory subunit PP(2A)-B56alpha, effects that were blocked by the D(1)-like antagonist SCH23390. Fenoldopam had no effect on cytosolic PP(2A) activity but decreased PP(2A)-B56alpha expression. In contrast, in immortalized proximal tubule cells of SHR, fenoldopam decreased PP(2A) activity in both membranes and cytosol but predominantly in the membrane fraction, without affecting PP(2A)-B56alpha expression; this effect was blocked by the D(1)-like antagonist SCH23390. We conclude that renal PP(2A) activity and expression are differentially regulated in WKY and SHR by D(1)-like receptors. A failure of D(1)-like agonists to increase PP(2A) activity in proximal tubule membranes may be a cause of the increased phosphorylation of the D(1) receptor in the SHR.

Animals↗
PubMed2000

Brasofensine NeuroSearch.

Brasofensine (NS-2214) is a dopamine reuptake inhibitor under development by NeuroSearch for the potential treatment of Parkinson's disease (PD) [178224]. The compound entered phase II trials in Denmark in November 1996, and phase I trials in the US in January 1996 [195505], [206604]. Bristol-Myers Squibb (BMS) had been codeveloping the compound until June 1999, when it decided to withdraw from the collaboration due to financial restraints of further regulatory requirements (such as additional toxicology documentation) [318365], [329665]. NeuroSearch was seeking licensing agreements with one or more international pharmaceutical companies to accelerate the development and marketing of brasofensine [187758] and had plans to meet with new potential partners for discussions concerning brasofensine licensing in late 1999 [337221]. A more complete evaluation of the effects of brasofensine was anticipated to be obtained through controlled trials, of at least 3 months duration, comparing it with a placebo and the marketed anti-Parkinson's drug, L-DOPA [317406]. In addition, further animal (monkey) tests were planned in order to document the safety of the drug in long-term treatment. These studies were expected to be discussed with the US FDA in October 1999 and, if satisfactory, the 3-month clinical trials were planned to commence in mid-2000 [337221]. At a meeting with the FDA during 1999, NeuroSearch presented plans for developing brasofensine alone. These were found to be satisfactory on condition that further preclinical studies were performed prior to any more clinical development [371542]. In August 2000, Lehman Brothers predicted worldwide sales of US $45 million in 2002 and US $175 million in 2003 [389229]. In February 1999, Lehman Brothers predicted the drug had a 35% probability of reaching market, with an estimated first launch date in 2002. The analysts predicted peak sales would occur in 2009, with sales of $250 million at that time [319225].

Animals↗