High viremia is associated with high levels of in vivo major histocompatibility complex class I Downregulation in rhesus macaques infected with simian immunodeficiency virus SIVmac239.

Human and simian immunodeficiency viruses (HIV and SIV) downregulate major histocompatibility complex class I (MHC-I) molecules from the surface of infected cells. Although this activity is conserved across viral isolates, its importance in AIDS pathogenesis is not clear. We therefore developed an assay to detect the level of MHC-I expression of SIV-infected cells directly ex vivo. Here we show that the extent of MHC-I downregulation is greatest in SIVmac239-infected macaques that never effectively control virus replication. Our results suggest that a high level of MHC-I downregulation is a hallmark of fast disease progression in SIV infection.

Glyceollin I, a novel antiestrogenic phytoalexin isolated from activated soy.

Glyceollins, a group of novel phytoalexins isolated from activated soy, have recently been demonstrated to be novel antiestrogens that bind to the estrogen receptor (ER) and inhibit estrogen-induced tumor progression. Our previous publications have focused specifically on inhibition of tumor formation and growth by the glyceollin mixture, which contains three glyceollin isomers (I, II, and III). Here, we show the glyceollin mixture is also effective as a potential antiestrogenic, therapeutic agent that prevents estrogen-stimulated tumorigenesis and displays a differential pattern of gene expression from tamoxifen. By isolating the individual glyceollin isomers (I, II, and III), we have identified the active antiestrogenic component by using competition binding assays with human ERalpha and in an estrogen-responsive element-based luciferase reporter assay. We identified glyceollin I as the active component of the combined glyceollin mixture. Ligand-receptor modeling (docking) of glyceollin I, II, and III within the ERalpha ligand binding cavity demonstrates a unique type II antiestrogenic confirmation adopted by glyceollin I but not isomers II and III. We further compared the effects of glyceollin I to the antiestrogens, 4-hydroxytamoxifen and ICI 182,780 (fulvestrant), in MCF-7 breast cancer cells and BG-1 ovarian cancer cells on 17beta-estradiol-stimulated expression of progesterone receptor and stromal derived factor-1alpha. Our results establish a novel inhibition of ER-mediated gene expression and cell proliferation/survival. Glyceollin I may represent an important component of a phytoalexin-enriched food (activated) diet in terms of chemoprevention as well as a novel therapeutic agent for hormone-dependent tumors.

Real data examples in statistical methods papers: Tremendously valuable, and also tremendously misvalued.

When a statistical methods paper is submitted to a journal for publication, examples in which the method is applied to real data are highly encouraged by many journals and in some cases are explicitly demanded. In this commentary, we argue that real data examples serve several useful purposes. However, we also argue that in many cases, particularly in the fields of genetics and genomics, there is an implicit or explicit expectation for examples to support purposes for which they are ill-suited and furthermore that these inappropriate expectations have negative consequences for the field. We conclude by noting that real data examples can be tremendously valuable and should continue to be used where appropriate, but that the demands for, expectations of, and conclusions drawn from them need to be scaled back.

Identification of the potent phytoestrogen glycinol in elicited soybean (Glycine max).

The primary induced isoflavones in soybean, the glyceollins, have been shown to be potent estrogen antagonists in vitro and in vivo. The discovery of the glyceollins' ability to inhibit cancer cell proliferation has led to the analysis of estrogenic activities of other induced isoflavones. In this study, we investigated a novel isoflavone, glycinol, a precursor to glyceollin that is produced in elicited soy. Sensitive and specific in vitro bioassays were used to determine that glycinol exhibits potent estrogenic activity. Estrogen-based reporter assays were performed, and glycinol displayed a marked estrogenic effect on estrogen receptor (ER) signaling between 1 and 10 microM, which correlated with comparable colony formation of MCF-7 cells at 10 microM. Glycinol also induced the expression of estrogen-responsive genes (progesterone receptor and stromal-cell-derived factor-1). Competitive binding assays revealed a high affinity of glycinol for both ER alpha (IC(50) = 13.8 nM) and ER beta (IC(50) = 9.1 nM). In addition, ligand receptor modeling (docking) studies were performed and glycinol was shown to bind similarly to both ER alpha and ER beta. Taken together, these results suggest for the first time that glycinol is estrogenic and may represent an important component of the health effects of soy-based foods.

Compatibility and stability of linezolid injection admixed with three cephalosporin antibiotics.

OBJECTIVE: To evaluate the physical compatibility and chemical stability of linezolid (Zyvox-Pharmacia) 200 mg/100 mL admixed with cefazolin sodium 1 gram, ceftazidime 2 grams, and ceftriaxone sodium 1 gram for 7 days at 4 degrees C and 23 degrees C. DESIGN: Controlled experimental trial. SETTING: Laboratory. INTERVENTIONS: The test samples were prepared by adding the required amount of the cephalosporin antibiotic to bags of linezolid injection 200 mg/100 mL. MAIN OUTCOME MEASURES: Physical stability and chemical stability based on drug concentrations initially and after 1, 3, 5, and 7 days of storage at 4 degrees C and 23 degrees C protected from light. RESULTS: All of the linezolid admixtures with cephalosporins were clear when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low and exhibited little change. The cefazolin sodium-containing samples were colorless throughout the study. The admixtures with ceftazidime and ceftriaxone sodium had a slight yellow tinge initially, and the room temperature samples became a frank yellow color after 5 days. The refrigerated samples did not change color. High-performance liquid chromatography analysis found little or no loss of linezolid in any sample stored at either temperature throughout the study. Cefazolin sodium and ceftazidime in the linezolid admixtures at 4 degrees C remained stable for 7 days, but at 23 degrees C cefazolin sodium was stable for 3 days and ceftazidime for only 24 hours before cephalosporin decomposition exceeded 10%. Ceftriaxone sodium was less stable in the admixtures; 10% loss occurred in 3 days at 4 degrees C and more than 20% loss occurred in 24 hours at 23 degrees C. CONCLUSION: Admixtures of linezolid 200 mg/100 mL with cefazolin sodium 1 gram and ceftazidime 2 grams were physically compatible and chemically stable for at least 7 days stored at 4 degrees C protected from light and for 3 days and 1 day, respectively, at 23 degrees C protected from light. Admixtures of linezolid with ceftriaxone sodium 1 gram exhibited a rapid rate of cephalosporin loss at 23 degrees C, which precludes admixture of the two drugs.

Compatibility screening of linezolid injection during simulated Y-site administration with other drugs and infusion solutions.

OBJECTIVE: To evaluate the physical compatibility of linezolid injection (Zyvox-Pharmacia) during simulated Y-site administration with 8 infusion solutions and 110 selected other drugs. DESIGN: Controlled experimental trial. SETTING: Laboratory. INTERVENTIONS: Five-milliliter samples of linezolid injection 2 mg/mL were mixed with 5 mL samples of the selected infusion solutions and the selected other drugs diluted in 5% dextrose injection, or, if necessary to avoid incompatibility with the diluent, 0.9% sodium chloride injection. MAIN OUTCOME MEASURES: Visual examinations of the samples were performed in normal fluorescent light with the unaided eye and using a Tyndall beam (high-intensity monodirectional light source) to enhance visualization of small particles and low-level haze. The turbidity of each sample was measured, and for samples that did not exhibit visible precipitation, the particle content was measured, as well. All of the samples were assessed initially and at 1 and 4 hours. RESULTS: All of the infusion solutions and most of the test drugs were physically compatible with linezolid injection during the 4-hour observation period. Physical incompatibilities resulted when linezolid injection was combined with five of the drugs: amphotericin B, chlorpromazine hydrochloride, diazepam, pentamidine isethionate, and phenytoin sodium. Precipitation, turbidity formation, and/or unacceptable changes in measured haze levels were observed. CONCLUSION: Linezolid 2 mg/mL was physically compatible for 4 hours at room temperature with all 8 infusion solutions tested and 105 of the drugs tested. Simultaneous Y-site administration of linezolid injection with the five drugs resulting in physical incompatibilities should be avoided.

Compatibility screening of hextend during simulated y-site administration with other drugs.

The physical compatibility of Hextend (6% hetastarch in lactated electrolyte injection, Abbott Laboratories, Abbott Park, Illinois) with 100 selected other drugs during simulated Y-site injection was evaluated by means of visual observation, turbidity measurement, and electronic particle content assessment when appropriate. Five-milliliter samples of Hextend injection were combined with 5 mL of 100 other test drugs that included anti-infectives, analgesics, antihistamines, diuretics, steroids, and other supportive care drugs undilted or diluted in 5% dextrose injection (or if necessary to avoid incompatibility of the secondary drug with the diluent, 0.9% sodium chloride injection). Visual examinations were performed with the unaided eye in normal diffuse fluorescent light and by means of a Tyndall beam (a high-intensity monodirectional light beam) to enhance visualization of small particles and low-level turbidity. The turbidity of each sample was measured as well. The particle content of samples with no visible incompatibility was measured. Evaluation of the samples was performed initially and at 1 and 4 hours after preparation. Ninety-seven of the 100 test drugs were compatible with Hextend injection during the 4-hour observation period. However, amphotericin B and diazepam resulted in precipitation, and sodium bicarbonate resulted in microcrystalline precipitation. Hextend injection should not be administered simultaneously with those incompatible drugs. Other drugs previously reported to be incompatible with 6% hetastarch in 0.9% sodium chloride injection were not found to be incompatible with Hextend.

Compatibility and stability of linezolid injection admixed with aztreonam or piperacillin sodium.

OBJECTIVE: To evaluate the physical compatibility and chemical stability of linezolid (Zyvox-Pharmacia) 200 mg/100 mL admixed with aztreonam (Azactam-Squibb) 2 grams and separately with piperacillin sodium (Pipracil-Lederle) 3 grams over 7 days at 4 degrees C and 23 degrees C. DESIGN: Controlled experimental trial. SETTING: Laboratory. INTERVENTIONS: Test samples were prepared by adding the required amount of aztreonam or piperacillin sodium to separate bags of linezolid injection 200 mg/100 mL. MAIN OUTCOME MEASURES: Physical compatibility and chemical stability based on drug concentrations initially and after 1, 3, 5, and 7 days of storage at 4 degrees C and 23 degrees C. RESULTS: All of the linezolid admixtures with aztreonam and with piperacillin sodium were clear when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low and exhibited little change throughout the study at both storage temperatures. High-performance liquid chromatography analysis found little or no loss of linezolid in any sample stored at either temperature throughout the study. Aztreonam in the linezolid admixtures was stable for 7 days, exhibiting less than 5% loss at 4 degrees C and 9% loss at 23 degrees C. Piperacillin sodium in the linezolid admixtures was stable for 7 days at 4 degrees C, exhibiting no loss, but was stable for only 3 days at 23 degrees C with losses of about 5%. Losses had increased to 9% to 12% after 5 days of storage at room temperature. CONCLUSION: Admixtures of linezolid 200 mg/100 mL with aztreonam 2 grams or piperacillin sodium 3 grams were physically compatible and chemically stable for at least 7 days stored at 4 degrees C and for 7 days or 3 days, respectively, at 23 degrees C.

Compatibility and stability of linezolid injection admixed with three quinolone antibiotics.

OBJECTIVE: To evaluate the physical compatibility and chemical stability of linezolid 200 mg/100 mL admixed with ciprofloxacin 400 mg, ofloxacin 400 mg, and levofloxacin 500 mg for seven days at 4 and 23 degrees C. METHODS: The test samples were prepared by adding the required amount of the quinolone antibiotic to bags of linezolid injection. Evaluations for physical and chemical stability were performed initially and after one, three, five, and seven days of storage at temperatures of 4 and 23 degrees C. Physical stability was assessed using visual observation in normal light and using a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. Chemical stability of the drugs was evaluated by using stability-indicating HPLC analytical techniques. RESULTS: The linezolid admixtures with levofloxacin and ofloxacin were clear and pale yellow when viewed in normal fluorescent room light, and slightly hazy with a green cast when viewed using a Tyndall beam. Measured turbidity and particulate content were low and exhibited little change. HPLC analysis found no loss of the drugs in any sample stored at either temperature throughout the study. The linezolid admixtures with ciprofloxacin stored at room temperature (23 degrees C) were clear and nearly colorless in normal room light and when viewed using a Tyndall beam. They exhibited little or no change in measured turbidity or particulate content during the study period. HPLC analysis found no loss of either drug in seven days. However, the refrigerated samples were only compatible for 24 hours and developed a gross white precipitate thereafter. CONCLUSIONS: Admixtures of linezolid 200 mg/100 mL with levofloxacin 500 mg and with ofloxacin 400 mg were physically compatible and chemically stable for at least seven days stored at 4 and 23 degrees C. Admixtures of linezolid with ciprofloxacin 400 mg were compatible and stable for seven days at 23 degrees C, but ciprofloxacin precipitation occurred after 24 hours stored under refrigeration. Linezolid/ciprofloxacin admixtures should not be stored under refrigeration.

Incompatibilities of lansoprazole injection with other drugs during simulated y-site coadministration.

The physical compatibility of lansoprazole injection with selected other drugs during simulated Y-site coadministration was evaluated by means of visual observation, turbidity measurement, and particle content assessment. Five-milliliter samples of lansoprazole 0.55 mg/mL in 0.9% sodium chloride injection were conbined with 5 mL of 112 other drugs including antineoplastics, analgesics, antiinfectives, and supportive-care drugs undiluted or diluted in 0.9% sodium chloride injection or 5 % dextrose injection for amphotericin B. Visual examinations were performed with the unaided eye in fluorescent light and by means of a Tyndall beam (a high-intesity, monodirectional light beam) to enhance the visualization of small particles and low-level trubidity. The turbidity of each sample was measured as well. Particle sizing and counting were performed on selected samples. Evaluation of the samples was performed initially and at 1 and 4 hours after preparation. Of the drugs tested, 92 were incompatible with lansoprazole 0.55 mg/mL in 0.9% sodium chloride injection during the 4-hour observation period. Gross precipitation or color changes visible in normal diffuse room light with the unaided eye occurred with 45 drugs. Phenomena not visible with the unaided eye, such as microprecipitation and /or increases in measured turbidity, occurred with 47 drugs. Only 20 drugs were found to be compatible for at least 4 hours. The measured turbidity of the lansoprazole control solutions and the compatible test samples, remained essentially unchanged throughout the study. In addition, the compatible samples exhibited no color change or substantial change in particle size and content throughout the observation period. In conbination with lansoprazole, only 20 drugs were considered to be physically compatible. Ninety-two drugs exhibited frank precipitation, microparticulate formation, color changes, or unacceptable increases of measured turbidity within 4 hours and should not be simultaneously coadministered with lansoprazole.

Compatibility and stability of linezolid injection admixed with gentamicin sulfate and tobramycin sulfate.

The purpose of this study was to evaluate the physical compatibility and chemical stability of linezolid 200 mg/100mL admixed with gentamicin sulfate 80 mg and tobramycin sulfate 80 mg over 7 days at 4 deg C and 23 deg C. The test samples were prepared by adding the required amount of the aminoglycoside antibiotic to bags of linezolid injection 200mg/100mL. Physical and chemical stability based on drug concentrations initially and after 1, 3, 5, and 7 days of storage at 4 deg C ad 23 deg C were evaluated. The linezolid-aminoglycoside admixtures were clear when viewed in normal fluorescent room light and with a Tyndall beam. Measured turbidity and particulate content were low and exhibited little change. The admixtures remained colorless throughout the study. High-performance liquid chromatography analysis indicated little or no loss of linezolid in any sample stored at either temperature throughtout the study. Gentamicin sulfate and tobramycin sulfate in the linezolid admixtures at 4 deg C remained stable for 7 days, but at 23 deg C gentamicin sulfate was stable for 5 days and tobramycin sulfate was stable for only 1 day before aminoglycoside losses exceeded 10%. Admixtures of linezolid 200mg/100mL with gentamicin sulfate 80 mg and tobramycin sulfate 80 mg were physically compatible and chemically stable for at least 7 days when stored at 4 deg C and for 5 days or 1 day, repectively, at 23 deg C.