Effects of hydroxycinnamic acids on blue color expression of cyanidin derivatives and their metal chelates.

Mechanisms to recreate many anthocyanin blue hues in nature are not fully understood, but interactions with metal ions and phenolic compounds are thought to play important roles. Bluing effects of hydroxycinnamic acids on cyanidin and chelates were investigated by addition of the acids to triglycosylated cyanidin (0-50×[anthocyanin]) and by comparison to hydroxycinnamic acid monoacylated and diacylated Cy fractions by spectrophotometry (380-700nm) and colorimetry in pH 5-8. With no metal ions, λmax and absorbance was greatest for cyanidin with diacylation>monoacylation>increasing [acids]. Hydroxycinnamic acids added to cyanidin solutions weakly impacted color characteristics (ΔE<5); while acylation (covalent acid attachment) resulted in ΔE 5-15. Triglycosylated cyanidin expressed blue color (pH 7-8), suggesting glycosylation pattern also plays a role. Al3+ chelation increased absorbance 2-42× and λmax≳40nm (pH 5-6) compared to added hydroxycinnamic acids. Metal chelation and aromatic diacylation resulted in the most blue hues.

Spectral and colorimetric characteristics of metal chelates of acylated cyanidin derivatives.

Colorants derived from nature are increasingly popular due to consumer demand. Anthocyanins are a class of naturally occurring pigments that produce red-purple-blue hues in nature, especially when interacting with metal ions and co-pigments. The role of various acylations of cyanidin (Cy) derivatives on color expression and stability of Al3+ and Fe3+ chelates in pH 6-7 were evaluated by spectrophotometry (380-700nm) and colorimetry (CIE-L∗a∗b∗) during dark, ambient storage (48h). Increased substitution generally increased λmax of Cy chelates: malonic acid monoacylationferulic-sinapic>sinapic-sinapic)>monoacylated (malonic≈sinapic>ferulic>p-coumaric).

Evaluating the role of metal ions in the bathochromic and hyperchromic responses of cyanidin derivatives in acidic and alkaline pH.

In many food products, colorants derived from natural sources are increasingly popular due to consumer demand. Anthocyanins are one class of versatile and abundant naturally occurring chromophores that produce different hues in nature, especially with metal ions and other copigments assisting. The effects of chelation of metal ions (Mg(2+), Al(3+), Cr(3+), Fe(3+), and Ga(3+)) in factorial excesses to anthocyanin concentration (0-500×) on the spectral characteristics (380-700nm) of cyanidin and acylated cyanidin derivatives were evaluated to better understand the color evolution of anthocyanin-metal chelates in pH 3-8. In all pH, anthocyanins exhibited bathochromic and hyperchromic shifts. Largest bathochromic shifts most often occurred in pH 6; while largest hyperchromic shifts occurred in pH 5. Divalent Mg(2+) showed no observable effect on anthocyanin color while trivalent metal ions caused bathochromic shifts and hue changes. Generally, bathochromic shifts on anthocyanins were greatest with more electron rich metal ions (Fe(3+)≈Ga(3+)>Al(3+)>Cr(3+)).

Soy-diet has beneficial effects on cardiovascular parameters that are independent of its lipid effect in male hypercholesterolemic rats.

Diet-induced atherosclerosis is lower in animals fed soy protein. The effects of various soy components have been extensively studied; however, little is known about the effect of crude soybean feeding on hypercholesterolemia-induced cardiovascular changes. This study investigated the effect of soy feeding on cardiovascular parameters in hypercholesterolemic male rats. Total cholesterol (TC), low density lipoprotein (LDL) and high density lipoprotein cholesterol (HDL), and triglyceride (TG) were measured. Rats were randomly assigned to control, high cholesterol (HC, 2% cholesterol) or HC + soy (HC+S) diets. In the HC+S group, rats received HC diet for 10 weeks followed by 2 weeks of soybean feeding. Arterial blood pressure, TC, TG, LDL and HDL were measured. TC, TG and LDL were higher in HC rats and were not significantly reduced by soybean feeding. Soy feeding reversed the HC-induced increase in arterial blood pressure and also restored the impaired vascular responses to acetylcholine in isolated aortic rings. Pre-incubation of HC+S aortic rings with L-NAME (10(-5) M for 20 min) partially reduced the effects of soy on acetylcholine responses, indicating that the beneficial vascular effects of dietary soy are partially mediated via nitric oxide pathway.

mtDNA ribosomal gene phylogeny of sea hares in the genus Aplysia (Gastropoda, Opisthobranchia, Anaspidea): implications for comparative neurobiology.

Sea hares within the genus Aplysia are important neurobiological model organisms; as more studies based on different Aplysia species are appearing in the literature, a phylogenetic framework has become essential. We present a phylogenetic hypothesis for this genus, based on portions of two mitochondrial genes (12S and 16S). In addition, we reconstruct the evolution of several behavioral characters of interest to neurobiologists to illustrate the potential benefits of a phylogeny for the genus Aplysia. These benefits include determination of ancestral traits, direction and timing of evolution of characters, prediction of the distribution of traits, and identification of cases of independent acquisition of traits within lineages. This last benefit may prove especially useful in understanding the linkage between behaviors and their underlying neurological bases.

Comparison of targeting a DUR letter intervention at pharmacists separate from and in addition to physicians.

OBJECTIVE: To examine the impact on dipyridamole prescribing of a letter mailed to pharmacists and/or physicians. DESIGN: Interrupted time series with control series. SETTING: State of Wisconsin. PARTICIPANTS: Physicians and pharmacists caring for patients who were prescribed dipyridamole. INTERVENTIONS: The state of Wisconsin was divided into four sections, three of which were designated as experimental regions (letter to physician only, letter to pharmacist only, and letter to both physician and pharmacist) and one of which served as a control region. MAIN OUTCOME MEASURES: Cost of drug per patient per month in ambulatory and long-term care populations. RESULTS: For 763 long-term care and 586 ambulatory Medicaid patients, letters sent to both physicians and pharmacists resulted in significant reductions in dipyridamole expenditures relative to the control group. For long-term care patients, interventions directed at both physicians and pharmacists produced significant reductions in dipyridamole prescribing relative to interventions directed at physicians alone or pharmacists alone. CONCLUSION: Future DUR letter interventions designed to change prescribing habits would be more effective if they targeted both physicians and pharmacists, particularly in the long-term care setting.

A controlled letter intervention to change prescribing behavior: results of a dual-targeted approach.

OBJECTIVE: To determine the effectiveness of a drug utilization review (DUR) letter intervention sent only to physicians, sent only to pharmacists, or sent to both physicians and pharmacists in changing physician prescribing behavior for dipyridamole. DATA SOURCES/STUDY SETTING: A Wisconsin Medicaid prescription drug database for data from March 1991 through May 1992 related to both long-term care and ambulatory patient settings. STUDY DESIGN: The effects of a DUR letter intervention were tested using a field study, pre-post, nonequivalent control group, quasi-experimental design. The effects of the letter intervention in terms of dipyridamole expenditures (dollars reimbursed to pharmacies by Medicaid), expenditures for related drugs (aspirin, ticlopidine, sulfinpyrazone) and numbers of patients for whom dipyridamole was discontinued were examined across three experimental groups and a control group. DATA COLLECTION/EXTRACTION METHODS: Dipyridamole expenditures for each study patient during a six-month preintervention and six-month postintervention period were collected from Medicaid prescription drug claims. Patients who had zero dipyridamole expenditures throughout the six-month postintervention period were classified as having had dipyridamole discontinued. PRINCIPAL FINDINGS: Letters sent to both physicians and pharmacists resulted in a greater percentage of patients discontinuing dipyridamole relative to controls and statistically significant differences in postintervention dipyridamole expenditures relative to controls in both the long-term care and ambulatory patient populations. CONCLUSIONS: Interventions that focus on another person in the drug use process in addition to the physician may have greater effects on a change in the prescribing of a targeted drug than letters to physicians alone.

Deducing the pattern of arthropod phylogeny from mitochondrial DNA rearrangements.

The origins of arthropods and the phylogenetic relationships among their three major living groups (atelocerates, crustaceans and chelicerates) are vigorously contended. To help resolve this, we determined mitochondrial gene arrangements for a chelicerate, a myriapod, two crustaceans, an onychophoran, a mollusc and an annelid, and compared them with published gene orders of other species. The result strongly supports the monophyly of Arthropoda and of Mandibulata (atelocerates plus crustaceans) and refutes the Uniramia (atelocerates plus onychophorans). Gene arrangement comparisons are emerging as a powerful new tool for resolving ancient phylogenetic relationships.

Biphasic viremia and viral gene expression in leukocytes during acute cytomegalovirus infection of mice.

Circulating leukocytes are important in dissemination of cytomegalovirus (CMV) infection in humans. In the mouse model of murine CMV infection (MCMV), it has been shown that infection peaks on days 5 to 7 after experimental infection, when 0.01 to 0.1% of the circulating leukocytes contain viral DNA. In our laboratory, MCMV DNA was detected by in situ hybridization predominantly in the mononuclear cells on day 6 after acute infection. Infectious virus was recovered from day 6 mononuclear fractions in 16 of 16 mice compared with that from day 6 polymorphonuclear fractions in 4 of 16 mice. An eclipse phenomenon was noted in the blood leukocytes by quantitative blot hybridization: the amount of MCMV DNA present was small on day 2, diminished on days 3 and 4, and then increased markedly on days 5 and 6 in both the mononuclear and polymorphonuclear fractions immediately following viral augmentation in the liver and spleen. MCMV immediate-early and glycoprotein B (late) transcripts were present in pooled mononuclear fractions only on day 6 of acute infection but not in pooled polymorphonuclear fractions. Collectively, these data demonstrate that (i) circulating leukocytes, predominantly mononuclear, are involved in dissemination of MCMV; (ii) a primary viremia with dissemination of MCMV to reticuloendothelial organs (liver and spleen) occurs and is followed by viral amplification and a subsequent, more intense secondary viremia; and (iii) immediate-early viral mRNA and glycoprotein B mRNA transcripts are detectable only during peak infection on day 6 in mononuclear leukocytes but not in polymorphonuclear leukocytes.

Evaluation of a DUR intervention: a case study of histamine antagonists.

Drug Utilization Review (DUR) programs aim to control inappropriate prescribing and drug costs, but there are few rigorous studies of their impact. This paper presents the evaluation results of a DUR intervention (excessive duration of full-dose histamine-2 receptor antagonists) using a quasi-experimental design. We observe a greater reduction of H2RA use in the intervention group than in the comparison group, and a reduction in drug expenditures which exceeded the cost of targeting and notifying prescribers. The success of DUR programs depends on both their efficiency and the drug issues under consideration; the use of a comparison group is critical in the evaluation of their impact.

The effects of nicotinamide and hyperbaric oxygen on skin flap survival.

Hyperbaric oxygen has been established as an acceptable treatment for the chronic healing wound. Nicotinamide has been shown to be angiogenic and accelerate the physiologic process following wounding. Therefore both nicotinamide and hyperbaric oxygen were evaluated to enhance flap survival in an island pedicle skin flap model. These two treatment modalities were evaluated alone and in combination to assess if there is an addictive effect to enhance flap survival. Forty Sprague-Dawley male rats (weight 300-350 grams) were treated for 14 days preoperatively 1 day post-operatively with either 400 mg of nicotinamide i.p. or saline i.p. On day 14, a 7 X 7 cm island pedicle skin flap was elevated ligating the left inferior epigastric neurovascular pedicle and were sutured in their normal position. Twenty animals then underwent hyperbaric oxygen treatments. Forty-eight hours post-operatively animals were re-anesthetized and were given a single injection of fluorescein (25 mg/kg) via the tail vein. The % survival of the flap and SEM of the groups are as follows: Saline 45.67 +/- 31.14, nicotinamide 85.30 +/- 9.24, saline-hyperbaric oxygen 76.70 +/- 9.42 and nicotinamide-hyperbaric oxygen 90.86 +/- 3.94 with statistical significance of p less than 0.01. Nicotinamide appears to be another acceptable therapeutic modality in the management of the acceleration of wound healing.

Nicotinamide enhances skin flap survival.

The effects of nicotinamide in an abdominal island pedicle skin flap were examined. A 7 x 7 cm island pedicle skin flap ligating the left inferior neurovascular pedicle was created on 50 male Sprague Dawley rats (250-275 grams) that were divided into five groups. Animals received either 0.6 cc of saline or doses of nicotinamide for 16 days (14 days preoperatively and 2 days postoperatively): 25 mg b.i.d., 50 mg b.i.d., 100 mg b.i.d. or 200 mg b.i.d. Forty-eight hours postoperatively each animal received 25 mg of Fluorescein via the tail vein. The area of necrosis was visualized and quantified and is presented as % survival. A one factor Fisher PLSD test was performed with a statistical significance of p less than 0.05 with the results as follows: saline 58.8%, 25 mg 68.6%, 50 mg 82%, 100 mg 80.8%, and 200 mg 86%. From this data it would appear that the angiogenic factor nicotinamide may increase random flap survival.

An examination of histamine-2 receptor antagonist use by Medicaid recipients in Wisconsin long-term care facilities.

The Wisconsin Drug Utilization Review Project used Medicaid claims data to examine the use of long-term, full doses histamine-2 receptor antagonists (H2RAs) among long-term care facility (LTCF) residents, ie, doses exceeding 800 mg per day of cimetidine or 150 mg per day of ranitidine for 12 weeks or more. Additional information about a small but representative sample of patients was obtained from consultant pharmacists by mail questionnaire. Of approximately 35,000 residents, there were 1,046 receiving long-term, full-dose H2RAs during 1984 at a cost of +405,848. No differences were noted between treated patients and the overall LTCF population by gender, age, level of care, or geographic locality. Among 387 patients receiving therapy for the last 3 months of 1984, over one half received antacids and over 20% received nonsteroidal anti-inflammatory drugs concurrently. According to survey respondents, almost one half of the patients had no diagnosis amenable to treatment by H2RAs. Diagnostic procedures conducted within 30 days prior to the initiation of H2RAs were hemoglobin/hematocrit assessment (performed on 53% of patients), stool testing (34%), radiological exam (23%) and endoscopy (8%). The results suggest that there is widespread use of long-term full-dose H2RAs in LTCFs for undocumented, inappropriate, and poorly supported diagnoses. Such findings are of concern to all persons charged with monitoring drug use in nursing homes because of the implications for both quality and cost of care. Information from this study will be used in designing a program to reduce inappropriate utilization of H2RAs, and Medicaid claims data will be used to monitor trends in utilization.