Overview of incretin hormones.

Incretins are hormones released by nutrients from the GI tract. They amplify glucose-induced insulin release. By raising circulating incretin levels, oral glucose provokes a higher insulin response than that resulting from intravenous glucose. The two most important incretin hormones are glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1). In patients with type 2 diabetes, the incretin effect is decreased, mainly due to loss of the GIP-regulated second phase of insulin secretion, and because of a decreased secretion of GLP-1. In addition to its insulinotropic effect, GLP-1 inhibits glucagon release, prolongs gastric emptying, and leads to decreases in body-weight, all of which explain the marked antidiabetogenic effect of this incretin hormone.     

Glucagon-like peptide-1 analogue LY315902: effect on intestinal motility and release of insulin and somatostatin

LY315902 is an analogue of GLP-1 that yields a reduced clearance and longer half-life. The aim of the study is to assess the effect of LY315902 on fasting gastrointestinal motility, somatostatin and insulin release. Sprague-Dawley rats were fitted with three bipolar electrodes, 15, 25 and 35 cm distal to the pylorus. The effect of LY315902 and GLP-1 on migrating myoelectric complex (MMC) cycle length, duration and propagating velocity of activity fronts was studied for 60 min in conscious animals. The effect of LY315902 and GLP-1 on fasting small bowel motility was dose-dependent and treatment with exendin (9-39)amide, a GLP-1 receptor antagonist, together with LY315902 and GLP-1 completely antagonised the inhibitory effect of LY315902 and GLP-1 on fasting small bowel motility. Pretreatment with the nitric oxide (NO) synthase inhibitor N(omega)-nitro-L-arginine (L-NNA) partly blocked the action of both LY315902 and GLP-1. Plasma insulin concentrations were not different from controls during infusion of LY315902 or GLP-1, while somatostatin concentrations were significantly higher during LY315902 and GLP-1 compared to saline. LY315902 has a longer duration of inhibitory action on the MMC than GLP-1, albeit similar effects on plasma insulin and somatostatin concentrations. The effect of LY315902 on motor control is mediated through the GLP-1 receptor and seems partly dependent on the L-arginine/NO pathway.     

Artificial neural networks for qualitative and quantitative analysis of target proteins with polymerized liposome vesicles

We investigate the feasibility of using the luminescence response of polymerized liposomes incorporating ethylenediaminetetraacetate europium(III) (EDTA-Eu(3+)) for monitoring protein concentrations in aqueous media. Quantitative analysis is based on the linear relationship between the luminescence enhancement of the lanthanide ion and protein concentration. Analytical figures of merit are presented for carbonic anhydrase, human serum albumin, gamma-globulins, and thermolysin. Qualitative analysis is based on the luminescence lifetime of the liposome sensor. This parameter, which follows well-behaved single exponential decays and provides characteristic values for each of the four studied proteins, demonstrates the selective potential for protein identification. Then partial least squares-1 and artificial neural networks are compared toward the quantitative and qualitative analysis of human serum albumin and carbonic anhydrase in binary mixtures without previous separation at the concentration levels found in aqueous humor.     

Airborne bacteria in Kuwait (1986–1988)

Totally 341 outdoors air samples were taken by Casella Airborne Sampler at a height of 7 m in the Allergy Centre of Kuwait between 1986 and 1988. Bacillus was detected in 85.3% of the samples. Micrococcus (71.3%), Staphylococcus albus (65.4%). Gram-positive rods (53.4%) were more prevalent than gram-negative rods (23.7%). Higher counts were seen in 1986 (500 CFU m^?3) compared to 1987 (407 CFU m^?3) and 1988 (369 CFU m^?3). Relatively higher counts were seen in August and September and a smaller peak was found in February and March. The correlation between the various types was always positive and was frequently highly significant. High counts were seen with strong winds. Among the meteorological factors, wind speed was the only significant factor. High average of bacteria counts were found when winds were blowing from the land (574 CFU m^?3) compared with the sea (346.5 CFU m^?3). Higher average counts were observed in the days with sand storms (1769 CFU m^?3), with rising sand (534.8 CFU m^?3) and the other days with dust phenomena, compared with clear weather (317 CFU m^?3).     

Randomization Analysis of Incomplete Data in Some Basic Designs

The first two randomization moments of W = Tt.S.S./(Tt.S.S. + Error S.S.) are derived in case of (a) a completely randomized design with one observation missing using (I) Yates method of fitting constants and (II) the available observations only and in case of (b) a randomized block design in which one treatment is tested twice by mistake in a block and another treatment is not tested at all in that block using (I) all the available observations and (II) the data after deleting the observation due to the treatment tested by mistake in place of another treatment in a block. It is concluded that in each of the two cases for a completely randomized design, the F-test is unbiased whereas in each of the two cases for a randomized block design the F-test is in general not unbiased. However, if one treatment is tested twice by mistake in randomly chosen plots of some block, the F-test is unbiased in both cases for a randomized block design. For a completely randomized design the F-test is found to be a good approximation to the corresponding randomized test if N ≧ 80 in case (I) whereas in case (II) this approximation is of the same accuracy as that of case (I) if N ≧ 90. For a randomized block design it is seen that in case (I), the F-test provides a good approximation to the corresponding randomization test if v≧r≧7 and in case (II) this approximation is of the same accuracy if r≧6 and r(v-1)≧45. The analysis of several uniformity trial data shows that for values of “N” in the neighbourhood of 50 the agreement of the first two moments of “W” under the randomization theory and normal theory are reasonably close in all the four cases considered.     

Somatostatin promotes accumulation of phospholipids in regenerating liver tissue of rats

Effects of somatostatin (SOM) on tissue contents of proteins, total lipids and phospholipids were investigated in regenerating and intact liver tissue of Y-59 rats. Whereas SOM inhibited protein accumulation in regenerating liver, the hormone evoked and increase in total lipids, and specially in phosphatidylcholine, phosphatidylethnolamine, phosphatidylserine (PS) and phosphatidylinositol (PI). Since the same effects were not seen when intact liver was analyzed, it is assumed that SOM acts primarily on tissue stimulated to rapid growth. The increase of PS+PI fractions indicates a specific effect of SOM on the metabolism of phosphatidylinositides. Such an effect might result from the interference of the hormone with the action of growth factors that accelerate phosphatidylinositol breakdown.     

Induction of a Peroxisomal Malate Dehydrogenase Isoform in Liver of Starved Rats

The influence of starvation on malate dehydrogenase (MDH) in rat liver was investigated. Native electrophoresis revealed two MDH isoforms in non-starved rats and three isoenzymes in starved rats. After sucrose density gradient centrifugation of cell organelles from liver, MDH activity was detected in the mitochondrial and cytosolic fractions from non-starved rats. However, additional activity was found in the peroxisomal fraction from starved rats. The latter was identified as the electrophoretically new isoform in starved animals. The three isoforms of malate dehydrogenase from hepatocytes were separated and partially purified by chromatography on DEAE-Toyopearl. Several kinetic and regulatory properties of the three isoforms were rather similar. It is suggested that the newly expressed isoform of MDH operates in the glyoxylate cycle of liver peroxisomes of food-starved animals.     

Differential expression of alternative splice variants of CTLA4 in Kuwaiti autoimmune disease patients

Cytotoxic T lymphocyte associated antigen4 (CTLA4) is a candidate susceptibility gene for the study of autoimmune diseases. The present study sought to explore the expression profile of the CTLA4 gene in autoimmune patients, such as rheumatoid arthritis (RA), systemic lupus erythematous (SLE) and Hashimoto's thyroiditis (HT), compared to healthy controls (HCs). A total of 88 (22 RA, 22 SLE 22 HT, 22 HCs) age-, gender- and ethnicity-matched individuals were recruited. The hypersensitive capillary electrophoresis method was employed to detect the CTLA4 splice variants. PCRs of the patient's cDNA using CTLA4-specific primers followed by cloning and sequencing were used to distinguish the various splice variants. The biochemical properties of all known CTLA4 variants were analysed using the ExPASy and ESEfinder programmes. Six alternatively spliced variants of the CTLA4 gene were detected in this study. These included mCTLA4-672, sCTLA4-562, N-CTLA4-292, L-CTLA4-277, ssCTLA4-214 and K-CTLA4-142 bp. K-CTLA4-142 bp and N-CTLA4-292 bp represented two novel splice variants of the CTLA4 gene. A reduction in the frequency of mCTLA4-672 bp and sCTLA4-562 bp was observed in SLE and RA patients compared to healthy controls. The shortest splice variant, K-CTLA4-142 bp, was predominantly detected in all of the tested cohorts, while the decreased expression of the N-CTLA4-292 bp variant was observed in the autoimmune subjects. The exonic splice enhancer motifs of the SRp40 protein were found exactly at the splice junction of wCTLA4 (-ACAGAGC-, 2.7) and K-CTLA4 (-TGAAAAG-, 3.37), and that of the SRp55 protein was found at the splice junction of L-CTLA4 (-TGTGTG-, 2.82). Our study highlights the discrepancies in the expression spectrum of the CTLA4 gene in autoimmune patients and healthy subjects. The abnormal expression pattern of the CTLA4 gene in autoimmune patients suggests that in addition to allelic variation, the expression pattern of CTLA4 could contribute to autoimmunity.     

Activity of the plant peptide aglycin in mammalian systems

A 37 residue peptide, aglycin, has been purified from porcine intestine. The sequence is identical to that of residues 27-63 of plant albumin 1 B precursor (PA1B, chain b) from pea seeds. Aglycin resists in vitro proteolysis by pepsin, trypsin and Glu-C protease, compatible with its intestinal occurrence and an exogenous origin from plant food. When subcutaneously injected into mice (at 10 microg.g(-1) body weight), aglycin has a hyperglycemic effect resulting in a doubling of the blood glucose level within 60 min. Using surface plasmon resonance biosensor technology, an aglycin binding protein with an apparent molecular mass of 34 kDa was detected in membrane protein extracts from porcine and mice pancreas. The polypeptide was purified by affinity chromatography and identified through peptide mass fingerprinting as the voltage-dependent anion-selective channel protein 1. The results indicate that aglycin has the potential to interfere with mammalian physiology.