The Effect of High-Dose Ascorbate Supplementation on Plasma Lipoprotein(a) Levels in Patients With Premature Coronary Heart Disease

Study Objective . To determine the efficacy of high-dose ascorbate supplementation in lowering lipoprotein(a) [Lp(a)] levels in patients with premature coronary heart disease (CHD). Design . Randomized, double-blind, placebo-controlled trial. Setting . Outpatient clinic. Patients . Forty-four patients with documented premature CHD. defined as confirmed myocardial infarction and/or angiographically determined stenosis of 50% or greater in at least one major coronary artery before age 60 years. Interventions . Patients were block randomized on the basis of age, gender, and screening Lp(a) concentrations to receive ascorbate 4.5 g/day or placebo for 12 weeks. Measurements and Main Results . High-dose ascorbate was well tolerated and produced a marked elevation in mean plasma ascorbate levels (+1.2 mg/dl; p<0.001). Multiple linear regression analysis revealed no significant effect of supplementation on postintervention Lp(a) levels (p=0.39) in a model that included treatment group assignment, and baseline Lp(a) levels. Conclusions . Our findings do not support a clinically important lowering effect of high-dose ascorbate on plasma Lp(a) in patients with premature CHD.     

Mechanisms of enhanced carbohydrate and lipid metabolism in adipose tissue in uremia.

OBJECTIVE: Hyperlipidemia is a permanent finding in advanced renal failure. It is supposed to be responsible for the accelerated arteriosclerosis and cardiovascular complications observed in patients with that disease. The background is partially determined, however, our knowledge in this matter is not yet satisfactory. METHODS: This study is based on the experimental rat model of chronic renal failure (CRF). Considering white adipose tissue (WAT) lipogenesis upregulation in CRF, along with the determination of acetyl coenzyme A carboxylase (ACC) and fatty acid synthase (FAS) genes expression, we have measured WAT gene expression for sterol regulatory binding protein 1 (SREBP-1) at the level of protein mass and mRNA abundance. Furthermore, we have determined glucose uptake, glucose-to-CO 2 conversion rate, and glucose translocator (GLUT-4) gene expression in WAT. RESULTS: Upregulation of both FAS and ACC gene expression was found in WAT of CRF rats. It was accompanied by WAT SREBP-1 gene overexpression. Moreover, we have observed the increased glucose uptake, glucose to CO 2 conversion rate, and GLUT-4 gene expression in WAT of CRF rats in comparison with controls. CONCLUSION: SREBP-1 gene overexpression may contribute to enhanced lipogenesis upregulation in WAT of CRF rats. It is not excluded that the increased WAT glucose metabolism activity is also induced by this mechanism, although there is no evidence currently to that end. We hypothesize that the increased WAT lipogenesis capacity could be a part of mechanism(s) leading to CRF-induced hyperlipidemia.     

Effect of polyacid aqueous solutions on photocuring of polymerizable components of resin-modified glass ionomer cements.

OBJECTIVES: Resin-modified glass ionomer cements (RMGI) are hybrid materials prepared by incorporation of polymerizable components (typically 2-hydroxyethyl methacrylate (HEMA) with possible addition of multifunctional methacrylates) into a conventional acid-base mixture (a polymeric acid with powdered calcium fluoro-aluminosilicate glasses). During setting, the photopolymerization process and the acid-base reaction affect each other. The aim of this work was to examine the effect of a 45% aqueous solution of poly(acrylic acid) (PAA) and the liquid component of a commercial glass ionomer cement on HEMA and triethyleneglycol dimethacrylate (TEGDMA) photopolymerization. METHODS: The polymerization was initiated by 2,2-dimethoxy-2-phenylacetophenone (DMPA) and camphorquinone (CQ)/coinitiator system. The reaction course was monitored under Ar and air by isothermal differential scanning calorimetry. RESULTS: The main effect of addition of polyacid solution (PAA and commercial) up to 10wt% to HEMA on the polymerization initiated with DMPA was earlier onset of autoacceleration. For the process initiated by the CQ-based system, the addition of 5wt% of PAA solution strongly accelerated the polymerization and increased the conversion, both in Ar atmosphere as well as in air. TEGDMA photopolymerization was not influenced or slightly retarded by the presence of 3wt% of PAA solution (the upper limit of solubility), depending on the initiating system used. SIGNIFICANCE: Under initiation conditions used in curing of commercial dental products (CQ-based two component initiating system), the presence of polyacid-aqueous solution in HEMA-based photocurable component increases markedly the polymerization rate and the conversion both in Ar atmosphere as well as in air. This result contributes to a characterization of the setting process of RMGIs.     

Cadmium,zinc, copper and metallothionein levels in human liver

The concentrations of cadmium, zinc, copper and metallothionein in the autopsy samples of liver among the inhabitants of Lód? (Poland) were determined. The cadmium levels were low in the range of 1.5 to 5.8 micrograms/g. The concentration of metallothionein determined by the Hg-method was high (0.160-1.665 mumol Hg/g); it was mainly a Zn-thionein. The percentage of hepatic zinc bound in the MT-fraction increased with the overall content of zinc in the liver. The elevation of zinc in the liver occurs in the proportion required for the saturation of metal-binding ligands of metallothionein. The role of cadmium remains less clear. Our results suggest that the metallothionein level in the liver increase significantly in response to elevated cadmium concentrations. This response, however, is in high excess to the demand which is justified stoichiometrically.     

Kinetics of polymerization of mixed diacetylene single crystals determined from dielectric measurements

Results of investigations on the kinetics of thermal polymerization of mixed single-crystalline diacetylenes are reported. The polymerization was studied at 333 K on a series of mixed 1 (pTS)– 3 (pFBS) crystals of various compositions. The polymer contents were determined from the measurements of electric permittivities of the samples during polymerization. A simple qualitative model was put forward to explain changes in the kinetics of polymerization as function of the composition of mixed crystals. At early stages of polymerization, the process of initiation of the growth of polymer chains seems to be dependent on the concentration of defects associated with a misfit between pTS and pFBS molecules.     

Role of nitric oxide in relaxation of the longitudinal layer of rectal smooth muscle

PURPOSE: This study was designed to investigate the role of nitric oxide in neurogenic relaxation of the longitudinal layer of human rectal smooth muscle. METHODS: Tissue was obtained from the mid rectum of patients undergoing anterior resection for carcinoma. Adjacent strips of longitudinal muscle were dissected and mounted in organ baths for isometric tension recording. In preliminary experiments to determine the response of strips to cholinergic, adrenergic, and potential excitatory agonists, strips were superfused with standard Krebs solution (37±0.5°C; pH, 7.4±0.05). Investigation of inhibitory, nonadrenergic noncholinergic responses required the addition of 3×10⁻⁶ M histamine to induce reproducible and stable tension for five-minute “test” periods, during which electrical field stimulation (EFS) and additional drugs were applied. In these experiments, strips were superfused with Krebs solution that contained atropine sulfate (3×10⁻⁶ M) and guanethidine (3×10⁻⁶ M). RESULTS: The response to cholinergic and adrenergic agonists was typical of nonsphincter specialized gastrointestinal smooth muscle. EFS elicited frequency-dependent, neurogenic (tetrodotoxin-sensitive) relaxations of precontracted strips, which were reduced in dose-dependent fashion by addition ofNω-nitro-l-arginine and restored by addition of 3×10 ⁻⁴ M l-arginine but not by d-arginine. Addition of exogenous nitric oxide (sodium nitroprusside) mimicked the relaxant response induced by EFS. CONCLUSION: Smooth muscle from the longitudinal layer of human rectum receives an intrinsic inhibitory innervation mediated by nitric oxide. Supported and financed by the Medical Research Council, United Kingdom. John Stebbing is in receipt of a Medical Research Council Clinical Training Fellowship. Read at the meeting of The American Society of Colon and Rectal Surgeons, Seattle, Washington, June 9 to 14, 1996.     

Role of fine-needle aspiration cytology and needle-core biopsy in the diagnosis of lobular carcinoma of the breast

Fine-needle aspiration cytology (FNAC) plays a key role in the preoperative diagnosis of carcinoma of the breast but is less reliable in the diagnosis of infiltrating lobular carcinoma. The method of diagnosis was reviewed in 56 patients with lobular carcinoma who had attended screening and symptomatic clinics. In 29 patients FNAC results demonstrated malignant cells; 15 of these had palpable disease and the mean tumour size was 21 mm. In 27 patients FNAC failed to demonstrate malignant cells; 13 lesions were palpable and the mean tumour size was 23 mm. Ten patients were diagnosed by needle-core biopsy when FNAC was not diagnostic. FNAC may fail to diagnose even large lobular carcinoma and needle-core biopsy is strongly recommended in this situation.     

Capsaicin cough sensitivity in allergic asthmatic patients increases during the birch pollen season.

BACKGROUND: A change in neural responsiveness may occur as the result of allergic inflammation in the lower airways as well as in the upper airways. In the lower airways, capsaicin cough sensitivity is known to reflect sensory neural reactivity. OBJECTIVE: The aim of this study was to establish whether allergic inflammation changes airway neural sensory reactivity during prolonged allergen exposure. METHODS: Ten nonsmoking patients with birch pollen-allergic asthma performed a capsaicin inhalation challenge twice, once in the off-pollen season and once during the pollen season. The number of coughs and symptoms induced by capsaicin were recorded and compared with those of healthy control subjects. RESULTS: The response to capsaicin, expressed as number of coughs, increased in a dose-dependent manner during both tests. Before the season, the response was similar to that of healthy control subjects, but during the pollen season, the reactivity was significantly increased. Variations in forced expiratory volume in 1 second were not significant before and after each challenge, and values did not change during the pollen season as compared with the winter season. CONCLUSIONS: Sensory reactivity in allergic asthmatic patients may be increased during prolonged allergen exposure as during the pollen season. This finding suggests that allergic inflammation in the lower and/or upper airways may trigger neurogenic mechanisms of significant clinical importance.     

Effect of Food on the Pharmacokinetics of a New Hydroxypropyl-β-Cyclodextrin Formulation of Itraconazole

Study Objective . To compare the pharmacokinetics of a single 100-mg oral dose of itraconazole administered as 10 ml of a 10-mg/ml itraconazole solution in hydroxypropyl-β-cyclodextrin under fasting versus postprandial conditions. Design . Open-label, two-way, randomized, crossover study. Setting . Janssen Research Foundation, Belgium. Patients . Twelve healthy volunteers. Interventions . Blood samples were obtained for pharmacokinetic analyses immediately before dosing and at regular intervals up to 96 hours after each dose. Blood and urine samples were obtained for hematologic, biochemical, and urinary safety analyses at baseline and at the end of the study. Measurements and Main Results . The mean peak plasma concentrations of both itraconazole and its active metabolite hydroxy-itraconazole were significantly higher under fasting conditions than under postprandial conditions. The mean times to peak concentration for both the parent compound and its metabolite were significantly shorter under fasting than under nonfasting conditions. The mean areas under the curve (AUC_0–∞ and AUC_{0–24 hrs}) were also significantly higher under fasting than under postprandial conditions. Conclusions . Our findings suggest that the higher bioavailability of this new formulation of itraconazole may be of benefit in seriously ill patients who are not able to ingest adequate quantities of food. The fact that the solution was also well tolerated and was not associated with clinically significant changes in any laboratory value further underscores the potential utility of this dosing form.