Long-term effects of foetal undernutrition on intermediary metabolism in growing lambs

The objective of this study was to investigate the effects of foetal undernutrition on the metabolism in growing lambs. Seven-month-old lambs whose mothers had been fed either restrictively (RN; n = 14) or adequately (AN; n = 6) in late gestation were fasted for three days. One hour before fasting and after 48 h and 72 h fasting, changes in plasma concentrations of metabolites, i.e. glucose, nonesterified fatty acids (NEFA), 3-beta-hydroxybutyrate (BOHB) and urea as well as hormones, i.e. insulin, the insulin-like growth factor (IGF-I) and leptin, were determined. Blood glucose, NEFA, urea, insulin, IGF-I and leptin were not different between the two groups of lambs. Unexpectedly, at the end of the 3 d fasting, in spite of lower NEFA concentration (1.6 +/- 0.03 vs. 1.9 +/- 0.05 mM in Groups RN and AN, respectively), the BOHB concentration in RN lambs (0.94 +/- 0.02 mM) was significantly higher than that in AN lambs (0.78 +/- 0.04 mM). This higher rate of BOHB production might be interpreted as perturbations in ketone body metabolism potentially induced by undernutrition during foetal life. However, more investigations are necessary to clarify this interrelationship.     

High-performance liquid chromatographic determination of lamivudine in human serum using liquid-liquid extraction; application to pharmacokinetic studies

A simple, fast, and sensitive high performance liquid chromatographic (HPLC) assay was developed for quantitation of lamivudine in human serum. Lamivudine is polar compound and its extraction from the human serum in previously published HPLC methods involved either protein precipitation or solid phase extraction techniques. However, existence of endogenous peaks which interfere with the drug or appeared as late eluting peaks and lead to long run time of analysis has been reported. Application of either an ion pairing agent in the mobile phase or time consuming column purge has been used in the published methods. Present paper describes liquid - liquid extraction of lamivudine and internal standard (famotidine) using dichloromethane-isopropyl alcohol (1:1, v/v) as an extracting solvent and salting out approach. The mobile phase was a mixture of phosphate buffer (0.05 M) containing triethylamine (1 mL/L, v/v; pH 3.5) and methanol (91:9, v/v) at a flow rate of 2.2 mL/min. The analysis was performed on a column (150 mm x 6 mm i.d.) which was packed with 5 microm particles of ODS packing material. Under these conditions no interference in the assay from any endogenous substance was observed. The limit of quantification was evaluated to be 5 ng/mL. Accuracy and precision of the method were also studied and the technique was shown to be selective and linear into the concentration range of 5-2500 ng/mL. This method has been used in two randomized crossover bioequivalence studies of 100 and 150 mg lamivudine preparations in 12 and 24 healthy volunteers, respectively.     

Cholesterol superlattice modulates CA4P release from liposomes and CA4P cytotoxicity on mammary cancer cells

Liposomal drugs are a useful alternative to conventional drugs and hold great promise for targeted delivery in the treatment of many diseases. Most of the liposomal drugs on the market or under clinical trials include cholesterol as a membrane stabilizing agent. Here, we used liposomal CA4P, an antivascular drug, to demonstrate that cholesterol content can actually modulate the release and cytotoxicity of liposomal drugs in a delicate and predictable manner. We found that both the rate of the CA4P release from the interior aqueous compartment of the liposomes to the bulk aqueous phase and the extent of the drug's cytotoxicity undergo a biphasic variation, as large as 50%, with liposomal cholesterol content at the theoretically predicted C(r), e.g., 22.0, 22.2, 25.0, 33.3, 40.0, and 50.0 mol % cholesterol for maximal superlattice formation. It appears that at C(r), CA4P can be released from the liposomes more readily than at non-C(r), probably due to the increased domain boundaries between superlattice and nonsuperlattice regions, which consequently results in increased cytotoxicity. The idea that the increased domain boundaries at C(r) would facilitate the escape of molecules from membranes was further supported by the data of dehydroergosterol transfer from liposomes to MβCD. These results together show that the functional importance of sterol superlattice formation in liposomes can be propagated to distal targeted cells and reveal a new, to our knowledge, mechanism for how sterol content and membrane lateral organization can control the release of entrapped or embedded molecules in membranes.     

Effect of Prepartum Supplementation of Selenium and Vitamin E on Serum Se, IgG Concentrations and Colostrum of Heifers and on Hematology, Passive Immunity and Se Status of Their Offspring

Forty heifers at the late stage of gestation were randomly assigned into five groups. Heifers were balanced for age, weight, and time of calving in each group. Four and 2?weeks before expected time of calving, the heifers were injected with 0?ml (C), 10?ml (T1), 20?ml (T2), 30?ml (T3), and 40?ml (T4) Se and VE supplements, respectively. Each milliliter of the supplement contained of 0.5?mg Se as sodium selenite and 50?IU of dl-alpha-tocopheryl acetate. Blood samples were collected from the heifers 4?weeks before expected calving and at calving day and from the calves at birth and 7?days of age. The serum Se and immunoglobulin G (IgG) concentrations, white blood cell and differential leukocyte counts were measured. The Se concentrations in the sera of the heifers before the injections of Se and VE supplements were the same among the groups (P?>?0.05), but after calving were significantly increased in the treated heifers (P??0.05). The white blood cell counts were higher in calves of heifers in groups T3 and T4 compared with the control group at 7?days of age (P?相似文献   

Comparative analysis of DNA polymorphisms and phylogenetic relationships among Syzygium cumini Skeels based on phenotypic characters and RAPD technique

The Indian black berry (Syzygium cumini Skeels) has a great nutraceutical and medicinal properties. As in other fruit crops, the fruit characteristics are important attributes for differentiation were also determined for different accessions of S. cumini. The fruit weight, length, breadth, length: breadth ratio, pulp weight, pulp content, seed weight and pulp: seed ratio significantly varied in different accessions. Molecular characterization was carried out using PCR based RAPD technique. Out of 80 RAPD primers, only 18 primers produced stable polymorphisms that were used to examine the phylogenetic relationship. A sum of 207 loci were generated out of which 201 loci found polymorphic. The average genetic dissimilarity was 97 per cent among jamun accessions. The phylogenetic relationship was also determined by principal coordinates analysis (PCoA) that explained 46.95 per cent cumulative variance. The two-dimensional PCoA analysis showed grouping of the different accessions that were plotted into four sub-plots, representing clustering of accessions. The UPGMA (r = 0.967) and NJ (r = 0.987) dendrogram constructed based on the dissimilarity matrix revealed a good degree of fit with the cophenetic correlation value. The dendrogram grouped the accessions into three main clusters according to their eco-geographical regions which given useful insight into their phylogenetic relationships.     

Identification of the motif in versican G3 domain that plays a dominant-negative effect on astrocytoma cell proliferation through inhibiting versican secretion and binding

This study was designed to investigate the mechanisms by which mutant versican constructs play a dominant-negative effect on astrocytoma cell proliferation. Although a mini-versican or a versican G3 construct promoted growth of U87 astrocytoma cells, a mini-versican lacking epidermal growth factor (EGF) motifs (versicanDeltaEGF) and a G3 mutant (G3DeltaEGF) exerted a dominant-negative effect on cell proliferation. G3DeltaEGF-transfected cells formed smaller colonies, arrested cell cycle at G(1) phase, inhibited expression of cell cycle proteins cdk4 and cyclin D1, and contained multiple nucleoli. In cell surface binding assays, G3 products expressed in COS-7 cells and bacteria bound to U87 cell surface. G3DeltaEGF products exhibited decreased binding activity, but higher levels of G3DeltaEGF products were able to inhibit the binding of G3 to the cell surface. G3DeltaEGF expression inhibited secretion of endogenous versican in astrocytoma cells and also inhibited the secretion of mini-versican in COS-7 cells co-transfected with the mini-versican and G3DeltaEGF constructs. The effect seems to depend on the expression efficiency of G3DeltaEGF, and it occurred via the carbohydrate recognition domain.     

Versican modulates embryonic chondrocyte morphology via the epidermal growth factor-like motifs in G3

This investigation was designed to characterize the effect of the extracellular matrix molecule versican on chondrocyte morphology, using the well-studied chondrocyte cell culture system. When cultured chondrocytes reverted or "dedifferentiated" to a fibroblast-like morphology, we found that versican expression was significantly enhanced. Transfection of chondrocytes, isolated from embryonic chicken sterna, with a chicken miniversican construct accelerated the reversion process, while expression of an antisense construct inhibited it. A mutant miniversican lacking two epidermal growth factor-like motifs (versicanDeltaEGF) promoted differentiation, as shown by morphological changes and changes in the expression of other extracellular matrix molecules. A truncated versican mutant, the G3DeltaEGF, a G3 domain lacking its two epidermal growth factor-like motifs, also enhanced differentiation. This effect is related to G3DeltaEGF-induced change in cytoskeleton, since transfected cells exhibited misassembly of actin filaments. This article thus provides the first evidence that versican modulates chondrocyte morphology via changes in cytoskeletal structure, and may imply that extracellular matrix molecules play an important role in cell differentiation.     

Effects of Aerobic Exercise during Pregnancy on Neurobehavioral Performances and Serum Levels of GDNF in Adult Male Mice Offspring

Neurophysiology - Clinical evidence indicates that physical activity during pregnancy may modulate the brain development and improve the neurobehavioral functions of the offspring. Nevertheless,...