Comparative studies on the substrate specificity of lecithin:cholesterol acyltransferase towards the molecular species of phosphatidylcholine in the plasma of 14 vertebrates

We have studied, in a prospective blinded fashion, the effects of regular and extended-release gemfibrozil on plasma lipoprotein and apolipoprotein (apo) levels in hypercholesterolemic subjects with decreased high density lipoprotein (HDL) cholesterol (C) levels. Study participants were men and women 19 to 80 years of age with baseline plasma low density lipoprotein (LDL) C levels > or = 4.5 mmol/l (175 mg/dl), HDL-C levels < or = 1.2 mmol/l (45 mg/dl), and triglyceride levels < or = 3.4 mmol/L (300 mg/dl). All subjects were stabilized on a diet for eight weeks prior to entry into two different protocols. In the first protocol 229 subjects were randomized to placebo or extended-release gemfibrozil (1200 mg/day) for 3 months (placebo trial). In the second protocol 655 subjects were randomized to regular or extended-release gemfibrozil (1200 mg/day) for 6 months (equivalency trial). Changes in lipids and apos were stratified by baseline HDL-C levels (< 0.9 mmol/l, and 0.9-12.2 mmol/l). In both studies, treatment with gemfibrozil, either regular or extended-release, was associated with significant (P < 0.05) decreases in plasma very low density lipoprotein (VLDL) C and triglyceride levels of 42-45% and 33-37%, respectively, in subjects with HDL-C level < 0.9 mmol/l, and of 38-47% and 32-39%, respectively, in patients with HDL-C levels of 0.9-1.2 mmol/l. Modest reductions from baseline in directly measured LDL-C levels were observed in both groups (3-6% and 8-9%, respectively). These reductions were less than those observed for calculated LDL-C (7-10% and 11%, respectively). For apo B, reductions were 11-14% and 16-17% in the two groups. HDL-C, apo A-I, and apo A-II levels increased by 15-16%, 5-6%, and 21-25%, respectively, in patients with HDL-C < 0.9 mmol/l, and by 6-7%, 2-3%, and 19-22%, respectively, in patients with HDL-C of 0.9-1.2 mmol/l. These differences in HDL-C levels reached statistical significance in the equivalency trial (P < 0.0001) and were independent of baseline triglyceride levels. Our data indicate that gemfibrozil, either regular or extended-release, is highly effective in lowering plasma triglyceride levels and increases HDL-C levels by approximately 15% in hypercholesterolemic patients with low HDL-C levels (< 0.9 mmol/l). Moreover, this agent lowers VLDL-C somewhat more than triglyceride, resulting in an underestimation of calculated VLDL-C reductions and in an overestimation of calculated LDL-C reductions. This agent also raises apo A-II levels much more than apo A-I levels.     

Small peptides as potent mimetics of the protein hormone erythropoietin

Random phage display peptide libraries and affinity selective methods were used to isolate small peptides that bind to and activate the receptor for the cytokine erythropoietin (EPO). In a panel of in vitro biological assays, the peptides act as full agonists and they can also stimulate erythropoiesis in mice. These agonists are represented by a 14- amino acid disulfide-bonded, cyclic peptide with the minimum consensus sequence YXCXXGPXTWXCXP, where X represents positions allowing occupation by several amino acids. The amino acid sequences of these peptides are not found in the primary sequence of EPO. The signaling pathways activated by these peptides appear to be identical to those induced by the natural ligand. This discovery may form the basis for the design of small molecule mimetics of EPO.     

All-optical clock distribution with synchronous frequency division and multiplication

A master optical clock from a mode locked laser is distributed to two slave twin section lasers. One slave laser divides the optical modulation frequency by 2, the other slave laser multiples the frequency by 2. It is also possible to vary the multiplication-division ratio in a slave laser using only DC control of the absorber of the twin section laser.<>     

Quantification of fluorophore concentration in tissue-simulating media by fluorescence measurements with a single optical fiber

Quantifying fluorescent compounds in turbid media such as tissue is made difficult by the effects of multiple scattering and absorption of the excitation and emission light. The approach that we used was to measure fluorescence using a single 200-microm optical fiber as both the illumination source and the detector. Fluorescence of aluminum phthalocyanine tetrasulfonate (AlPcS4) was measured over a wide range of fluorophore concentrations and optical properties in tissue-simulating phantoms. A root-mean-square accuracy of 10.6% in AlPcS4 concentration was attainable when fluorescence was measured either interstitially or at the phantom surface. The individual effects of scattering, absorption, and the scattering phase function on the fluorescence signal were also studied by experiments and Monte Carlo simulations.     

Effects of dietary Spirulina maxima on endothelium dependent vasomotor responses of rat aortic rings

The aim of this study was to evaluate the effects of Spirulina maxima on vasomotor responses of aorta rings from male Wistar rats fed on a purified diet. For this purpose, the animals (weighing 200-240 g) were allocated randomly in two groups. One receiving purified control diet (A) and the other receiving purified diet containing 5% Spirulina (B). Purified diets were according to American Institute of Nutrition guidelines and adjusted to Spirulina protein content. All animals were fed (20 g/day/rat) during two weeks, receiving water ad libitum and 12 h. light-dark cycles. Spirulina maxima effects were evaluated by concentration-response (CR) curves of aorta rings with or without endothelium to phenylephrine (PE), both in presence and absence of indomethacin (Indom) or indomethacin plus L-NAME (Indom. + L-NAME), and to carbachol (CCh). Aorta rings with endothelium from group B showed, relative to corresponding rings from group A: 1) a significant decrease in the maximal tension developed in response to PE. 2) this decrease was reverted by Indom. 3) Indom. + L-NAME induced an additional increase in the contractile responses to PE. 4) a significant shift to the left of the CR curve to CCh. No significant differences were observed in the tension developed in response to PE in rings without endothelium from either group. These results suggest that Spirulina maxima may decrease vascular tone by increasing the synthesis and release of both a vasodilating cyclooxygenase-dependent product of arachidonic acid and nitric oxide, as well as by decreasing the synthesis and release of a vasoconstricting eicosanoid from the endothelial cells.     

Antenatal ambroxol treatment does not prevent the respiratory distress syndrome in premature infants

The effectiveness of ambroxol in the prevention of neonatal respiratory distress syndrome and in reducing the need for intermittent mandatory ventilation and oxygen therapy was studied in 88 mothers whose infants was born between 24 and 34 weeks of gestation and who were randomized either for treatment with ambroxol (group A = 42) or served as control (group B = 46). There were no significant differences in the mean gestational age, birth weight or Apgar score between the two groups. We found no significant differences in occurrence of respiratory distress syndrome (55% vs 45%), in support by intermittent mandatory ventilation (71% vs 72%) or oxygen therapy (74% vs 75%) at 12 h of age between groups A and B. CONCLUSION: This study does not suggest the efficacy of antenatal ambroxol treatment both for the prevention of neonatal respiratory distress syndrome and for the reduction of its severity.     

Life-threatening transient neonatal Beh?et's disease

This case report describes transient neonatal Beh?et's disease, with life-threatening complications in the neonate. Male Baby R developed blood-streaked diarrhoea 5 days after birth, followed by recurrent severe scarring orogenital ulceration and vasculitic skin lesions. In this sixth week of life, he developed stridor leading to a respiratory arrest and necessitating assisted ventilation. No infective cause was isolated. Baby R responded well to i.v. and subsequent oral steroid therapy. At 8 weeks old he had fully recovered and remains well. Baby R's mother was not previously known to have Beh?et's disease. During the pregnancy, she began to suffer orogenital ulceration, associated with skin lesions typical of Beh?et's disease. Mild orogenital ulceration has become recurrent.     

Sex hormones differentially regulate isoforms of UDP-glucuronosyltransferase

PURPOSE: To investigate the role of sex hormones in the regulation of UDP-glucuronosyltransferase (UGT). METHODS: We examined liver from adult, prepubertal, gonadectomised and gonadectomised plus hormone replaced rats of both sexes. Immunohistochemistry and immunoblots were performed using a polyclonal UGT antibody to a number of family 1 and family 2 UGT isoforms. Northern blot analysis was performed utilising cDNA probes to family 1 and family 2 isoforms. RESULTS: Immunohistochemistry demonstrated variations in intensity and distribution of staining in the hormonally manipulated rats. Immunoblots showed variations in individual band intensity between rat groups. Immunoblots using a more specific antibody (anti-17 beta-hydroxysteroid UGT, which recognises UGT2B3 and UGT2B2) demonstrated marked differences between male and female rats and significant alterations after gonadectomy and testosterone replacement in the male rats. In northern analysis, UGT2B3 and 2B1 mRNA were significantly higher in adult males than females, and in prepubertal males compared to prepubertal females. In male rats, gonadectomy resulted in a 45-53% reduction in UGT2B3 and 2B1 levels respectively, which increased significantly with testosterone treatment to greater than normal adult levels. No change in UGT2B3 or 2B1 occurred after gonadectomy in females. In contrast, UGT1*1 mRNA tended to be higher in adult female and prepubertal female rats than in their male counterparts. In females, gonadectomy resulted in significant up-regulation of UGT1*1, while gonadectomy plus oestradiol treatment resulted in markedly reduced levels. UGT1*1 mRNA was not significantly altered by gonadectomy in males. CONCLUSIONS: This study demonstrates the differential effects of sex hormones on the expression of isoforms from the two phylogenetically distinct UGT families.     

Computer-assisted sperm analysis for assessing initial semen quality and changes during storage at 5 degrees C

Computer-assisted sperm analysis equipment was used to evaluate bull sperm initially in a modified Tyrode's solution, in Cornell University extender, and in egg yolk-glycerol-Tris extender (following cooling and storage in the latter two extenders). Two ejaculates of semen were collected from each of eight bulls. Semen was divided into aliquots using a factorial arrangement. The semen, diluted to approximately 20 x 10(6) sperm/ml, was loaded into two 20-micron chambers, and six microscope fields from each chamber were videotaped for each treatment of each ejaculate of semen. Eight sperm characteristics analyzed with the Hamilton Thorne integrated visual optical system (Hamilton Thorne, Beverly, MA) were reported, and some of these characteristics differed significantly among bulls. The initial values of motile sperm in modified Tyrode's solution, Cornell University extender, and egg yolk-glycerol-Tris extender were 87, 79, and 66%; little change followed cooling and storage at 5 degrees C in the latter two extenders. Also, there was a small but significant decline in sperm velocity during 3 d of storage. Hyperactive sperm increased slightly during storage. The procedures used can rapidly and accurately measure many sperm characteristics in fresh semen and in semen stored in egg yolk extenders, and differences among bulls can be detected.