It is vital to screen the germplasm of crop plants for salt stress tolerance so as to utilize them in breeding programs. Accordingly, in the present study, twenty diverse inbred lines, parents of mapping populations of pearl millet were chosen to determine the phenotypic contrasts for seed yield, which can open the way for developing salt tolerance QTLs. Parents were grown in two summer seasons (late and early) with VPD ≥ 2 kPa, and one rainy season with VPD < 2 kPa, during flowering and grain filling under saline (150 and 200 mM) and non-saline (0 mM) conditions. Salinity delayed flowering time by a fortnight in the summer seasons but only 5–6 days in the low VPD rainy season. Salinity decreased grain yield by 86% in late-summer and 80% in early-summer, but less than 70% in rainy season. GY penalty was higher than vegetative biomass under saline conditions especially in summer season when the evaporative demand was very high. It appears that reproduction and grain filling are sensitive to high temperature that can compound the effect of salinity and high VPD. GY of inbreds under salinity was not better in comparison with non-saline conditions. DOF and grain density (thousand grain weight) were found as important correlated traits under salinity. Also, GY was affected significantly if VPD increased during flowering time.
BACKGROUND: Hyaluronic acid (HA) fillers have been proposed as alternatives to other temporary skin fillers, such as bovine collagen, for treating facial skin lines and for providing lip augmentation. Several types of commercial HA fillers are now available in many countries. They include Restylane, which is produced by microbiologic engineering techniques, and Hylaform, which is HA extract derived from rooster combs. They have been approved for use in several countries, but not currently in the United States. There are no recommendations to perform pretreatment skin testing by the manufacturers. OBJECTIVE: Our purpose is to describe and comment on our experiences with Hylaform and Restylane fillers. Observation of any side effects and skin testing results were documented. METHODS: Between September 1996 and September 2000, 709 patients were treated with Hylaform and Restylane and were followed up clinically for at least 1 year. Three of these patients (0.42%) developed delayed skin reactions. Three other patients were referred for evaluation of their skin reactions from other practitioners. Five of these 6 patients agreed to skin testing of their forearms. RESULTS: In the 5 patients tested, challenge intradermal skin testing was positive in 4 patients; the reactions started approximately 8 weeks after injection. CONCLUSIONS: There was a slight incidence of delayed inflammatory skin reactions to two HA fillers. Both of these reactions occurred after the first and repeat injections. Challenge skin testing was positive in 4 of 5 tested patients. 相似文献
Access to specialty care is critical for patients with advanced stage lung cancer. This study assessed access to cancer specialists and cancer treatment in a broad population of patients with advanced stage lung cancer.
Materials and Methods
Two study samples were extracted from 2 claims databases and analyzed independently: patients aged ≥ 18 years with de novo diagnosis of metastatic lung cancer in the MarketScan database between 2008 and 2014 (commercially insured adult patients; n = 22,268); and patients aged ≥ 65 years in the Surveillance, Epidemiology, and End Results–Medicare database with a diagnosis of advanced non–small-cell lung cancer between 2007 and 2011 (Medicare-insured elderly patients; n = 9651). The study period spanned from 6 weeks before the first lung biopsy tied to the initial lung cancer diagnosis until the end of continuous health insurance enrollment, or data availability, or death.
Results
Among the commercially insured adults (MarketScan), most patients were seen by a cancer specialist within a month of first lung biopsy (80%), 12% were never seen by a cancer specialist, and 6% did not receive cancer-directed therapy. Among the Medicare-insured elderly patients (SEER–Medicare), the proportions were 79%, 4%, and 10%, respectively. Patients seen by a cancer specialist were more likely to receive cancer-directed therapy (95% vs. 92%, P < .001 and 92% vs. 38%, P < .001, respectively).
Conclusion
Between 4% and 12% of patients with advanced stage lung cancer do not have appropriate access to cancer specialist, which appears to negatively affect access to optimal and timely treatment. 相似文献
Purpose Eritoran (E5564) is a glycophospholipid that acts as a toll-like receptor 4 (TLR4) antagonist that is being tested as a treatment
for severe sepsis and septic shock. In the blood, eritoran binds to plasma lipoproteins altering its pharmacokinetic and pharmacodynamic
(PD) effects in vivo. The purpose of this study was to determine the influence of changes in plasma cholesterol and triglyceride concentrations
on the plasma pharmacokinetics and ex vivo activity of eritoran following single intravenous bolus dosing of eritoran to healthy female rabbits fed either a regular
chow diet or a cholesterol-enriched diet. This was done with eritoran administered as stable micelle formulations of mean
hydrodynamic diameters of 8 or 27 nm).
Methods Female New Zealand White rabbits were fed a standard diet for 7 days and then randomly assigned either a regular chow diet
[regular-diet (n = 9)] or a cholesterol-enriched diet [cholesterol-diet (n = 12)] for an additional 7 days. Following feeding of these diets a single intravenous bolus dose of eritoran (0.5 mg/kg)
formulated into either “small micelles” (8 nm in diameter) or “large micelles” (27 nm in diameter) was administered to regular-fed
and cholesterol-fed rabbits. Serial blood samples were obtained prior to eritoran administration and at the following times
post injection: 0.083 (5 min), 1, 2, 4, 8, 10, 24, 48 and 72 h. Plasma was analyzed for eritoran concentrations using LC/MS/MS.
Total plasma cholesterol (TC) and triglyceride (TG) levels were quantified using enzymatic kits. Plasma eritoran pharmacokinetic
(PK) parameters were estimated by non-compartmental analysis using the WinNonlin nonlinear estimation program. To analyze
PD activity, whole blood obtained at 0.083 (5 min), 2, 24, 48 and 72 h following eritoran administration was assessed for
ex vivo activity by measuring the ability of 1 and 10 ng/ml LPS to elicit TNF-α release.
Results Total plasma cholesterol and triglyceride levels were significantly higher in cholesterol-fed rabbits compared to the rabbits
fed a regular chow diet. Diet had no effect on the estimated plasma PK parameters. However, PD activity of both small and
large micelle eritoran as measured by an ex vivo challenge dose of 1 ng/ml LPS was reduced in blood of cholesterol-fed rabbits compared to normal-fed rabbits. Comparison
of PK parameters for small and large micelles indicated that small micelles had increased AUC0–72 h, decreased plasma clearance and increased initial concentration (measured at 5 min post administration) compared to the large
micelle formulation. Consistent with this observation, eritoran formulated into small micelles had significantly greater ex vivo activity than large micelles and was independent of TC and TG concentrations.
Conclusions These findings suggest that plasma pharmacokinetics and activity of eritoran maybe influenced by eritoran micelle size and
plasma TC and TG concentrations. 相似文献
Purpose. The objectives of this study are to determine the plasma distribution of free and chylomicron-associated BIRT 377 within rats and rabbits.
Methods. For the rat studies free and chylomicron-associated BIRT 377 was incubated in plasma from CD 1 non-fasted rats for 60 minutes at 37°C. Following incubation the plasma was separated into its lipoprotein and lipoprotein-deficient plasma (LPDP) fractions by three different methods and analyzed for BIRT 377 content by HPLC. For the rabbit studies New Zealand fasted white rabbits (3 kg; n = 4) were administered an intravenous dose of free BIRT 377 (1 mg/kg). Following administration, serial blood samples were obtained and the plasma was analyzed for BIRT 377. The plasma collected at the 0.083-h time point was separated into each of its lipoprotein fractions and analyzed for BIRT 377.
Results. 37.8 ± 1.2% of the original drug amount incubated in rat plasma was recovered within the lipoprotein-rich fraction. 41.5 ± 0.4% of the original chylomicron-associated drug concentration incubated was recovered within the lipoprotein-rich fraction. The percentage of drug recovered within the TRL fraction was significantly greater following the incubation of chylomicron-associated BIRT 377 compared to free BIRT 377. In addition, BIRT 377 apparently follows a two-compartment pharmacokinetic model following single intravenous dose administration to rabbits.
Conclusions. These findings suggest that plasma lipoprotein binding of BIRT 377 is evident and may be a factor in evaluating the pharmacological fate of this drug when administered to patients that exhibit changes in their plasma lipoprotein lipid. 相似文献
We studied and compared the efficiency of induction aneurysm in apo E mice by using high fat diet and Ang II. Aneurysm induced
in 6 week old male apo E −/− mice by subcutaneous release of Ang II injection for 45 days. Also, aneurysm was induced in three
month old male apo E by administration of high fat diet for a period of three months. No difference in body weight in Ang
II treated mice. But, increase in body weight and mean arterial blood pressure observed in high fat diet group animals. Highly
significant increase in total cholesterol, TG, LDL and significant decrease in HDL level were observed in Ang II treated animals.
Significant increase in total cholesterol, but no changes in TG, LDL, HDL levels were observed in high fat diet group. Higher
percentage of circulating monocytes was observed in ang II treated group but more number of circulating lymphocytes were observed
in high fat diet group in FACS analysis. In histopathology, intimal layer of abdominal aorta was completely replaced by chronic
inflammatory cells particularly macrophages (80%) which appeared as foam cells and lymphocytes (20%) in ang II treated animals.
Degradation of elastin, infiltration of lymphocytes, chondrocytes and cellular migration towards media were observed in the
abdominal aorta of high fat diet group. Real time analysis and immunofluorescence assay supports over expression of Vcam 1
Icam1, MCP 1and MMP2 genes were observed in Ang II treated animals. In immunofluorescence assay, over expression of Mac 3
protein specific for macrophages was observed in abdominal aorta of ang II treated animals, but over expression of CD45.1
& 45.2 proteins specific to lymphocytes were observed in high fat diet group. Based on our observations, Ang II induced aortic
aneurysm by recruiting/ proliferating circulating monocytes by up regulating Icam-1, Vcam -1 and MCP-1. Also, ang II involved
in degradation of elastin in the abdominal aorta by up regulation of MMP2 to promote agranulocytes migration in the intimal
layers. Epithelial cell hyperplasia with accumulation of fatty fluids (cyst) was observed in seminal vesicle and ventral prostate
of high fat treated animals. Fatty degeneration, germ cell apoptosis and infiltration giant cells were observed in the testes
of high fat diet group. As per available literature these observations were not reported with high fat diet treatments with
apo E models. High fat diet induced aneurysm prominently in abdominal, thoracic aorta and extensive plaque formation was observed
in femoral and renal arteries. Administration of high fat diet containing cholesterol induced aneurysm in apo E mice model
also efficient method to rule out the pathogenesis of aortic aneurysm when compared with angiotensin. 相似文献
1-(2'-Oxo/thiobarbiturinyl)-3-arylidenylchalcones (3-14) were synthesized by the condensation of different aromatic aldehydes with 5-acetyl-2-oxo/thiobarbituric acid (1 resp. 2) and various 1-acetyl-5-arylidenyl-3-(2'-oxo/thiobarbiturinyl)-2-pyrazolines (15-26) were synthesized by cyclisation of compounds 3-14 with hydrazine hydrate. The newly synthesized compounds showed anticonvulsant activity ranging from 40% to 90%. Compound 23 showed the maximum activity being more potent than the reference drug 1-acetyl-5-(P-methoxyphenyl)-3-(2'-thiobarbiturinyl)-2-pyrazoline. 相似文献
This review article addresses the recently discovered finding that cholesteryl ester transfer protein (CETP) can facilitate the transfer of water-insoluble drugs between different lipoprotein subclasses. This protein, which is often referred to as lipid transfer protein I (LTP I), is involved in the lipid regulation of lipoproteins. It is responsible for the facilitated transfer of core lipoprotein lipids, cholesteryl ester and triglycerides, and approximately one-third of the coat lipoprotein lipid, phosphatidylcholine, between different plasma lipoproteins. The human body appears to recognize exogenous water-insoluble drugs as lipid-like particles, which suggests that these compounds may interact with lipoproteins just like endogenous plasma lipids, and thus their transfer between lipoproteins may be facilitated by plasma CETP. Patients with a variety of diseases (i.e. diabetes, cancer, AIDS) often exhibit hypo- and/or hypercholesterolemia and triglyceridemia, commonly referred to as dyslipidemias, which result in changes in their plasma lipoprotein-lipid composition and concentration. The interaction of water-insoluble drugs with these dyslipidemic lipoproteins may be responsible for the differences seen in the pharmacokinetics and pharmacodynamics of the drug within different diseased patient populations. It is possible that these differences may be linked to the ability of CETP to transfer these compounds from one lipoprotein to another. This review examines the current understanding of the relationship between CETP activity and the lipoprotein distribution of a number of compounds (e.g. amphotericin B and cyclosporine A). It further suggests that additional research will expand our understanding of the role of CETP to explain other functions in lipophilic drug distribution and metabolism. 相似文献
Depression is common among patients who abuse both opiates and cocaine, and its treatment has had mixed success. This study compares buprenorphine-maintained patients with lifetime major depressive disorder (MDD, N = 53) with those never depressed (ND, N = 96) on cocaine and opiate-free urines during a 12-week outpatient double-blind, placebo-controlled, randomized clinical trial. The 149 subjects were assigned to four groups: 1) desipramine (DMI) + contingency management (CM); 2) DMI + noncontingency management (NCM); 3) placebo + CM; and 4) placebo + NCM. Depression assessments included Hamilton Depression Rating Scale, Center for Epidemiological Studies Depression Inventory, and Structured Clinical Interview for DSM-IV interview for diagnosis of lifetime MDD. Urine toxicologies were performed thrice weekly and the CES-D was performed monthly. The MDD group had a larger proportion of females (45% vs 21%, P = 0.02) and were more likely to be married (13.2% vs 7.3%, P = 0.02) than the ND group. Treatment retention did not vary by depression status. Hierarchical Linear Modeling found that depressive symptoms decreased comparably across the four treatment groups. Although participation in CM improved drug-free urines more for patients with MDD than for the ND group (Z = 2.44, P = 0.01), treatment with DMI was significantly more efficacious for the ND group than for the MDD group (Z = -2.89, P = 0.003). These results suggest that patients with MDD may respond better to behavioral treatments such as CM than to desipramine plus buprenorphine. The ND cocaine-abusing, opiate-dependent patients may be more responsive to the anticraving effects of DMI. 相似文献