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Biomedical subjects

Fang Zhang

Publications and source records attributed to Fang Zhang.

At least 37 records · Page 2Linked to original sources

Effect of quality improvement on racial disparities in diabetes care.

BACKGROUND: Racial disparities in care are well documented; information regarding solutions is limited. We evaluated whether generic quality improvement efforts were associated with changes in racial disparities in diabetes care. METHODS: Using insurance claims and electronic medical record data, we identified 5101 whites and 1987 blacks with diabetes mellitus receiving care within a multispecialty group practice from 1997 to 2001. We assessed rates of annual low-density lipoprotein cholesterol level testing, low-density lipoprotein cholesterol level control (<130 mg/dL [<3.37 mmol/L]), statin therapy, annual glycosylated hemoglobin level testing, glycosylated hemoglobin level control (<7.0%), and annual dilated eye examinations. We used logistic regression models with generalized estimating equations to adjust for race, year, race x year interactions, age, and sex. RESULTS: Rates of annual low-density lipoprotein cholesterol level testing increased from 39% to 64%, while the white-black disparity decreased from 14% to 4%; rates of low-density lipoprotein cholesterol level control increased from 15% to 43%, while the white-black disparity decreased from 9% to 6% (P<.001 for both race x year interactions). Statin therapy rates increased from 20% to 37%; however, black patients remained less likely than white patients to receive therapy. The 1997 rates of annual glycosylated hemoglobin level testing (76%) and annual eye examinations (74%) were high, and there was no white-black disparity over time. Rates of glycosylated hemoglobin level control remained low (31%), and the white-black disparity remained constant at 10%. CONCLUSIONS: Racial disparities were diminished in some aspects of diabetes care following variably successful quality improvement, but differences in the use of statins and glycemic level control persisted. Reducing disparities may require a focus on minority health.

Black People↗

Physician alerts to increase antidepressant adherence: fax or fiction?

BACKGROUND: Many managed care organizations use feedback based on electronically maintained claims data to alert physicians to potential treatment problems, including patient medication nonadherence. However, the efficacy of such interventions for improving adherence among patients treated for depression is unknown. METHODS: We examined an antidepressant compliance program consisting of faxed alerts to physicians beginning May 2003 using interrupted time series analysis to evaluate its impact on rates of antidepressant adherence between May 2002 and May 2004 among members of the managed care plan of Harvard Pilgrim Health Care, which is a health plan operating in 3 states in New England, with corporate headquarters in Wellesley, Mass. The program alerted prescribing physicians to patients with gaps of more than 10 days in refilling antidepressant prescriptions during the first 180 days of treatment. Our outcome measures were rates of nonadherence among patients with refill gaps of more than 10 days ("delayed refill") and proportion of days without treatment within the first 180 days of treatment. RESULTS: A total of 13 128 patients (> or = 18 years of age) who were starting treatment with antidepressants met the study criteria. Rates of nonadherence among patients with delayed refills remained constant (P = .22) over the 2-year study period, averaging 75% (95% confidence interval, 72.7%-77.3%). Rates of antidepressant nonadherence significantly increased over time (P = .04), with an average of 40% (95% confidence interval, 38.4%-41.6%) of days without dispensed antidepressants available during treatment episodes. CONCLUSIONS: Using real-time pharmacy information to alert physicians regarding patient adherence was not successful in increasing antidepressant adherence rates among members of the managed care plan. Effectiveness of electronically triggered, patient-specific, faxed feedback should be carefully evaluated before widespread implementation, because faxes are insufficient as a stand-alone policy tool.

Adult↗

Racial disparities in access after regulatory surveillance of benzodiazepines.

BACKGROUND: We examined the effects of a prescription-monitoring program on benzodiazepine access among Medicaid enrollees living in neighborhoods of different racial composition. METHODS: We used interrupted time series and logistic regression to analyze data from noninstitutionalized persons aged 18 years or older (N = 124 867) enrolled continuously in New York Medicaid 12 months before and 24 months and 7 years after initiation of the program. We used census data to identify the racial composition of the neighborhoods. Outcome measures were nonproblematic use (short term, within dosing guidelines), potentially problematic use (>120 days' use or more than twice the recommended dose), and pharmacy hopping (filling prescriptions for the same benzodiazepine in different pharmacies within 7 days). RESULTS: There was a sudden, sustained reduction in benzodiazepine use in all the neighborhoods after the program's introduction. Despite the lowest rates of baseline use, enrollees in predominantly (> or = 75%) black neighborhoods experienced the highest rates of discontinuation after introduction of the program. This difference remained 7 years after policy initiation. Compared with white participants, black participants were more likely to discontinue nonproblematic (odds ratio, 1.78; 95% confidence interval, 1.47-2.17) and potentially problematic (odds ratio, 1.77; 95% confidence interval, 1.45-2.17) benzodiazepine use, after adjusting for sex, eligibility status, neighborhood poverty, and baseline use. The program almost completely eliminated pharmacy hopping in all racial groups, although less among white participants (82.6%) vs black participants (88.7%). CONCLUSIONS: A systematic benzodiazepine prescription-monitoring program reduced inappropriate prescribing, with a stronger effect in predominantly black neighborhoods despite lower baseline use. The policy may have resulted in an unintended decrease in nonproblematic use that disproportionately affects black populations.

Adult↗

Value of mink vomit model in study of anti-emetic drugs.

AIM: To establish a new, reliable vomit model of minks. METHODS: Adult male minks were randomly divided into 8 groups (n=6): cisplatin (7.5 mg/kg) intraperitoneal injection (i.p.) group, copper sulfate (40 mg/kg) intragastric injection (i.g.) group, apomorphine (1.6 mg/kg) subcutaneous injection (s.c.) group, and 18 Gy whole-body X-irradiation group, ondansetron injection group (2 mg/kg i.p.) 30 min later followed by cisplatin (7.5 mg/kg) i.p., normal saline (NS) i.p. injection control group, metoclopramide injection group (4 mg/kg i.p.) 30 min later followed by apomorphine (1.6 mg/kg) s.c., NS i.g. control group. The frequency of retching and vomiting was calculated. After behavioral experiment, distribution of 5-HT in the ileum was detected by immunohistologic method. RESULTS: Cisplatin, apomorphine, copper sulfate and X-irradiation administered to minks evoked a profound emetic response in the animals. However, retching and vomiting were significantly inhibited by pretreatment with ondansetron and metoclopramide in cisplatin and copper sulfate groups (P=0.018). Immunohistologic result showed that 5-HT released from enterochromaffin cells (EC cells) was involved in vomiting mechanism. CONCLUSION: Mink vomit model has a great value in studying the vomiting mechanism and screening new antiemetic drugs.

Animals↗

[Metabolism of recombinant CHO-GS cell reducing of toxic effect of ammonia].

The toxic effect of ammonia on rCHO-GS cell decreased obviously due to the transfection of GS system in serum-free culture. The maximum cell density, 15.6 x 10(5) cells/mL was obtained in the culture with 1.42 mmol/L ammonia. The growth of rCHO-GS cell was inhibited with an increased ammonia concentration. However, a cell density of 8.9 x 10(5) cells/mL was obtained when the concentration of ammonia was 12.65mmol/L. The intracellar metabolic pathways were affected due to the decrease of the toxic effect of ammonia on rCHO-GS cell. With the increase of initial ammonia concentration from 0.36mmol/L to 12.65mmol/L, the yield coefficients of cell to glucose and lactate to glucose decreased. The activities of hexokinase (HK), pyruvate kinase (PK), and lactate dehydrogenase (LDH) increased by 43%, 140% and 25%, respectively, indicating that the utilization of glucose increased and the glycolysis pathway was more prone to efficient energy metabolism pathway. An increased activity of glutamate-pyruvate aminotransferase (GPT) showed that the conversation from glutamate to alpha-ketoglutarate was shifted to glutamate-pyruvate transamination pathway. The deamination pathway was inhibited due to a decreased activity of glutamate dehydrogenase. In addition, the number of cells in G0/G1 phase increased and the specific production rate of recombinant protein increased by 2.1-fold with the increase of initial ammonia concentration from 0.36mmol/L to 12.65mmol/L.

Ammonia↗

Differential effect of early or late implementation of prior authorization policies on the use of Cox II inhibitors.

BACKGROUND: State Medicaid programs introduce many types of prescribing restrictions to manage pharmaceutical use and expenditure. Little is known about the differential effect of implementing prior authorization (PA) policies at market entry versus waiting until several years later when prescribing behavior may already be established. OBJECTIVES: We sought to examine the impact on overall use of Cox II inhibitors of PA policies implemented at market entry versus at least 2 years after market entry. RESEARCH DESIGN: We quantified Cox II inhibitor and nonselective nonsteroidal anti-inflammatory drug (NSAID) utilization for state Medicaid programs from January 1996 to September 2003. We used generalized estimating equations, Tukey's studentized range test and segmented linear regression on state Medicaid programs to determine the significance of changes in medication use. MEASURES: The primary end point was the number of defined daily doses (DDD) per 1000 population per day. RESULTS: Six states implementing prescribing restrictions for Cox II inhibitors at market entry had the lowest rates of uptake, averaging 10.9 DDD/1000/d. Twelve states adopting restrictions more than 2 years after market entry experienced declines in use from 23.0 DDD/1000/d before to 13.9 DDD/1000/d after the restrictions (P < 0.01). The 17 states that had never restricted access had the highest utilization, averaging 29.0 DDD/1000/d. CONCLUSION: Implementing prescribing restrictions at market entry of Cox II inhibitors was effective in restricting uptake. Despite the difficulty in changing well-established prescribing patterns, utilization in states implementing policies 2 years after market entry approached that of the early adopting states within 1 year. Clinical outcomes of such policies remain unknown.

Anti-Ulcer Agents↗

Trends and geographic variation of opiate medication use in state Medicaid fee-for-service programs, 1996 to 2002.

BACKGROUND: Although studies have documented hospital and surgical service geographic variability, prescription use geographic variability is largely unknown. Opiate pain medications are widely used, particularly because the promulgation of clinical guidelines promoting aggressive pain treatment. This study describes temporal and interstate variability in aggregate prescription opiate medication use within U.S. Medicaid programs. METHODS: A dataset of 49 states' fee-for-service (FFS) Medicaid prescription drug dispensing records from 1996 to 2002 was compiled and used to quantify medication dispensing examining all opiates, controlled release oxycodone, and methadone. The defined daily dose (DDD) per 1000 FFS Medicaid adult enrollees per day was calculated for all opiate medication categories. A market basket of nonpain prescription medications was constructed for comparison. Rates, trends, and the coefficient of variation were determined overall, by year and for each state. RESULTS: From 1996 to 2002, overall use of opiate pain medications increased 309%. The market basket use increased 170%. Total opiate dispensing varied widely from state to state, with a range of 6.9 to 44.1 DDD/1000/d in 1996, and 7.1 to 165.0 DDD/1000/d (a 23-fold difference) in 2002. The coefficient of variation was 49.6 in 2002. Controlled release oxycodone and methadone had a greater rate of increase compared with all opiates. CONCLUSIONS: The dispensing of opiate medications in Medicaid programs increased at almost twice the rate of nonpain-related medications during the 7-year study period. Large, unexplained geographic variation in aggregate use exists. The impact of Medicaid cost-containment strategies on utilization and outcomes should be investigated.

Analgesics, Opioid↗

Rice GTPase OsRacB: potential accessory factor in plant salt-stress signaling.

As the sole ubiquitous signal small guanosine triphosphate-binding protein in plants, Rop gene plays an important role in plant growth and development. In this study, we focus on the relationship between the novel rice Rop gene OsRacB and plant salt tolerance. Results show that OsRacB transcription is highly accumulated in roots after treatment with salinity, but only slightly accumulated in stems and leaves under the same treatment. Promoter analysis showed that OsRacB promoter is induced by salinity and exogenous salicylic acid, not abscisic acid. To elucidate its physiological function, we generated OsRacB sense and antisense transgenic tobacco and rice. Under proper salinity treatment, sense transgenic plants grew much better than the control. This suggests that overexpression of OsRacB in tobacco and rice can improve plant salt tolerance. But under the same treatment, no difference could be observed between OsRacB antisense plants and the control. The results indicated that OsRacB is only an accessory factor in plant salt tolerance.

Abscisic Acid↗

Halofenate is a selective peroxisome proliferator-activated receptor gamma modulator with antidiabetic activity.

Halofenate has been shown previously to lower triglycerides in dyslipidemic subjects. In addition, significant decreases in fasting plasma glucose were observed but only in type 2 diabetic patients. We hypothesized that halofenate might be an insulin sensitizer, and we present data to suggest that halofenate is a selective peroxisome proliferator-activated receptor (PPAR)-gamma modulator (SPPARgammaM). We demonstrate that the circulating form of halofenate, halofenic acid (HA), binds to and selectively modulates PPAR-gamma. Reporter assays show that HA is a partial PPAR-gamma agonist, which can antagonize the activity of the full agonist rosiglitazone. The data suggest that the partial agonism of HA may be explained in part by effective displacement of corepressors (N-CoR and SMRT) coupled with inefficient recruitment of coactivators (p300, CBP, and TRAP 220). In human preadipocytes, HA displays weak adipogenic activity and antagonizes rosiglitazone-mediated adipogenic differentiation. Moreover, in 3T3-L1 adipocytes, HA selectively modulates the expression of multiple PPAR-gamma-responsive genes. Studies in the diabetic ob/ob mouse demonstrate halofenate's acute antidiabetic properties. Longer-term studies in the obese Zucker (fa/fa) rat demonstrate halofenate's comparable insulin sensitization to rosiglitazone in the absence of body weight increases. Our data establish halofenate as a novel SPPARgammaM with promising therapeutic utility with the potential for less weight gain.

3T3-L1 Cells↗

Francisella tularensis in rodents, China.

A total of 420 rodents in China were examined for Francisella tularensis by polymerase chain reaction. The infection rates were 4.76% in total, and 11.65%, 10.00%, 6.56%, 1.77%, and 0% in Jilin, Xinjiang, Heilongjiang, Inner Mongolia, and Zhejiang, respectively. Sequence analysis showed that all the detected agents belonged to F. tularensis subsp. holarctica.

Animals↗

Spatial restriction of PDK1 activation cascades by anchoring to mAKAPalpha.

The muscle A-kinase anchoring protein (mAKAP) tethers cAMP-dependent enzymes to perinuclear membranes of cardiomyocytes. We now demonstrate that two alternatively spliced forms of mAKAP are expressed: mAKAPalpha and mAKAPbeta. The longer form, mAKAPalpha, is preferentially expressed in the brain. mAKAPbeta is a shorter form of the anchoring protein that lacks the first 244 amino acids and is preferentially expressed in the heart. The unique amino terminus of mAKAPalpha can spatially restrict the activity of 3-phosphoinositide-dependent kinase-1 (PDK1). Biochemical and genetic analyses demonstrate that simultaneous recruitment of PDK1 and ERK onto mAKAPalpha facilitates activation and release of the downstream target p90RSK. The assembly of tissue-specific signaling complexes provides an efficient mechanism to integrate and relay lipid-mediated and mitogenic activated signals to the nucleus.

3-Phosphoinositide-Dependent Protein Kinases↗

Evaluation of gene expression endpoints in the context of a Xenopus laevis metamorphosis-based bioassay to detect thyroid hormone disruptors.

Thyroid hormones (TH) are important in growth, development and the maintenance of proper cellular metabolism in vertebrates. Amphibian metamorphosis is completely dependent on TH and forms the basis of a screen for thyroid axis disrupting chemicals that currently relies on external morphological endpoints and changes in thyroid gland histology. The requirement for TH-dependent gene expression makes it possible to augment this screen through the addition of molecular endpoints. In order to do this, gene selection, choice of sampling time, tissue sensitivity, and their relationship to morphological change must all be considered. We exposed stage 54 Xenopus laevis tadpoles to a concentration series of the THs, thyroxine (T4) and 3,5,3'-triiodothyronine (T3), and three known TH antagonists, methimazole, propylthiouracil (PTU), and perchlorate. The agonists significantly accelerated metamorphosis as defined by developmental stage attained after 14 days. In contrast, the TH antagonists significantly delayed metamorphosis at 14 days and caused an increase in thyroid gland size at day 8. We assessed the changes in steady-state mRNA levels of thyroid hormone receptor alpha- and beta-isoforms and the basic transcription element binding (BTEB) protein by quantitative real-time polymerase chain reaction. Three tissues (brain, tail and hindlimb) were analyzed at 24, 48 and 96 h and we found that TH receptor, TRbeta, and BTEB were the most sensitive gene transcripts for the TH agonists, whereas only TRalpha displayed significant changes upon antagonist exposure. We detected differences in tissue-specific responses between the two agonists. We matched the concentrations of T3 and T4 that elicited similar biological responses at 14 days and compared the induction of gene expression. At 96 h, the TRbeta and BTEB expression response to T3 and T4 was similar in the tail. In contrast, T3 elicited no concentration-dependent changes in TRbeta and BTEB expression in the brain, whereas T4 elevated their expression. The tail showed the highest correlation between TH concentration and morphological outcome whereas the brain was the most sensitive to antagonist treatment. Only methimazole and perchlorate showed significant changes in TRalpha gene expression in the brain whereas PTU did not suggesting differences in cellular mechanisms of action. The greatest effect on gene expression occurred within 48 h with many of the hormone-dependent changes disappearing by 96 h. This study accentuates the need to examine multiple tissues and provides critical information required for optimization of exposure regimens and endpoint assessments that focus on the detection of disruption in TH-regulatory systems.

Animals↗

Two-dimensional kinetics regulation of alphaLbeta2-ICAM-1 interaction by conformational changes of the alphaL-inserted domain.

The leukocyte integrin alphaLbeta2 mediates cell adhesion and migration during inflammatory and immune responses. Ligand binding of alphaLbeta2 is regulated by or induces conformational changes in the inserted (I) domain. By using a micropipette, we measured the conformational regulation of two-dimensional (2D) binding affinity and the kinetics of cell-bound intercellular adhesion molecule-1 interacting with alphaLbeta2 or isolated I domain expressed on K562 cells. Locking the I domain into open and intermediate conformations with a disulfide bond increased the affinities by approximately 8000- and approximately 30-fold, respectively, from the locked closed conformation, which has similar affinity as the wild-type I domain. Most surprisingly, the 2D affinity increases were due mostly to the 2D on-rate increases, as the 2D off-rates only decreased by severalfold. The wild-type alphaLbeta2, but not its I domain in isolation, could be up-regulated by Mn2+ or Mg2+ to have high affinities and on-rates. Locking the I domain in any of the three conformations abolished the ability of divalent cations to regulate 2D affinity. These results indicate that a downward displacement of the I domain C-terminal helix, induced by conformational changes of other domains of the alphaLbeta2, is required for affinity and on-rate up-regulation.

Animals↗

NixPb1-x nanowire arrays: effects of annealing.

Ni(x)Pb(1-x) nanowire arrays were successfully fabricated by AC electrodeposition within the nanopores of ordered porous alumina films prepared by a two-step anodization. Transmission electron microscopy analyses showed that the Ni-Pb nanoarrays are polycrystalline with dimension uniformity around 20 nm in diameter and lengths up to several micrometers. X-ray diffraction results revealed that the face-centered-cubic (fcc) Ni and fcc Pb peaks are detected when the Ni component (x) is below 0.71, indicating that the Ni(x)Pb(1-x) nanoarrays do not form metastable phase alloy. Hysteresis loops determined by vibrating sample magnetometer indicated that the Ni(x)Pb(1-x) nanoarrays obtained possess obvious magnetic anisotropy, and the perpendicular coercivity was lower than that of pure Ni nanowries before and after annealing. Annealing under magnetic field was carried out to examine the effect of a magnetic field on magnetic properties using an electromagnet field up to 0.3 T.

Journal Article↗

Depletion of GAK/auxilin 2 inhibits receptor-mediated endocytosis and recruitment of both clathrin and clathrin adaptors.

Cyclin G-associated kinase (GAK/auxilin 2), the ubiquitous form of the neuronal-specific protein auxilin 1, is an essential cofactor for the Hsc70-dependent uncoating of clathrin-coated vesicles. We have now investigated the effect of knocking down GAK in HeLa cells by vector-based small hairpin RNA. Functionally, depletion of GAK caused a marked decrease in internalization of both transferrin and epidermal growth factor and altered mannose 6-phosphate receptor trafficking, but had little effect on the recycling of transferrin receptor back to the plasma membrane. Structurally, depletion of GAK caused a marked reduction in perinuclear clathrin associated with the trans-Golgi network and in the number of clathrin-coated pits on the plasma membrane, and reduced clathrin exchange on the few clathrin-coated pits that remained. Surprisingly, while clathrin depletion does not prevent adaptors from assembling on the membrane, depletion of GAK caused a dramatic reduction in AP2 and epsin on the plasma membrane and AP1 and GGA at the trans-Golgi network. A similar effect was caused by expression of a dominant negative Hsp70 mutant. These results suggest that GAK, in conjunction with Hsc70, not only uncoats clathrin-coated vesicles and induces clathrin exchange on clathrin-coated pits, but also mediates binding of clathrin and adaptors to the plasma membrane and the trans-Golgi network.

Adaptor Proteins, Vesicular Transport↗

Acute toxicity of nano- and micro-scale zinc powder in healthy adult mice.

The purpose of this study is to evaluate the acute toxicity of oral exposure to nanoscale zinc powder in mice. The healthy adult male and female mice were gastro-intestinally administered at a dose of 5 g/kg body weight with two size particles, nanoscale zinc (N-Zn) and microscale zinc (M-Zn) powder, while one group mice treated with sodium carboxy methyl cellulose was used as the control. The symptoms and mortality after zinc powder treatment were recorded. The effects of particles on the blood-element, the serum biochemical level and the blood coagulation were studied after 2 weeks of administration. The organs were collected for histopathological examination. The N-Zn treated mice showed more severe symptoms of lethargy, vomiting and diarrhea in the beginning days than the M-Zn mice. Deaths of two mice occurred in the N-Zn group after the first week of treatment. The mortalities were confirmed by intestinal obstruction of the nanoscale zinc aggregation. The biochemical liver function tests of serum showed significantly elevated ALT, AST, ALP, and LDH in the M-Zn mice and ALT, ALP, and LDH in the N-Zn mice compared with the controls (P<0.05), which indicated that the liver damage was probably induced by both micro- and nano-scale zinc powders. The clinical changes were observed in the two treated group mice as well. The levels of the above enzymes were generally higher in the M-Zn mice than in the N-Zn mice, which implied that M-Zn powder could induce more severe liver damage than N-Zn. The biochemical renal function tests of serum BUN and CR in the M-Zn mice markedly increased either compared with the N-Zn mice or with the controls (P<0.05), but no significant difference was found between the N-Zn and the control mice. However, severe renal lesions were found by the renal histopathological examination in the N-Zn exposed mice. Therefore, we concluded that severe renal damage could occur in the N-Zn treated mice, though no significant change of blood biochemical levels occurred. Blood-element test showed that in the N-Zn mice, PLT and RDW-CV significantly increased, and HGB and HCT significantly decreased compared to the controls, which indicated that N-Zn powder could cause severe anemia. Besides the pathological lesions in the liver, renal, and heart tissue, only slight stomach and intestinal inflammation was found in all the zinc treated mice, without significant pathological changes in other organs.

Animals↗