Prior exercise increases basal and insulin-induced p38 mitogen-activated protein kinase phosphorylation in human skeletal muscle.

We have examined the effects of insulin on p38 mitogen-activated protein kinase (MAPK) phosphorylation in human skeletal muscle and the effects of prior exercise hereon. Seven men performed 1-h one-legged knee extensor exercise 3 h before the initiation of a 100-min euglycemic-hyperinsulinemic (600 pmol/l) clamp. Glucose uptake across the legs was measured with the leg balance technique, and muscle biopsies were obtained from the rested and exercised vastus lateralis before and during insulin infusion. Net glucose uptake during the clamp was approximately 50% higher (P < 0.05) in the exercised leg than in the rested leg. Insulin induced a modest sustained 1.2- and 1.3-fold increase (P < 0.05) in p38 MAPK phosphorylation in the rested and exercised legs, respectively. However, p38 phosphorylation was approximately 50% higher (P < 0.05) in the exercised compared with the rested leg before and during insulin infusion. We conclude that a physiological concentration of insulin causes modest but sustained activation of the p38 MAPK pathway in human skeletal muscle. Furthermore, the stimulatory effect of exercise on p38 phosphorylation is persistent for at least 3 h after exercise and remains evident during subsequent insulin stimulation. Because p38 MAPK has been suggested to play a necessary role in activation of GLUT-4 at the cell surface, the present data may suggest a putative role of p38 MAPK in the increased insulin sensitivity of skeletal muscle after exercise.     

Molecular differentiation of two morphological variants of Gracilaria salicornia

Xia in 1986 combined Gracilaria salicornia, G. canaliculata (G. crassa), G. cacalia and G. minor into one species: G.salicornia. Two morphological variants of G. salicornia were collectedfrom different localities in Malaysia. Variant A collected from Morib,Selangor grew on the roots of Avicennia. The samples showed absenceof main axis; segmented constrictions throughout; cylindrical or slightlycompressed thalli. Variant B was collected from the mudflats of TanjungTuan, growing on rocks, coral or forming mats on the mud. Plants showedabsence of main axis; segments were not constricted throughout the plant(if present only slightly articulated at the upper part), branching wasdichotomous or irregular; cylindrical or slightly compressed thalli. Thetechnique of Random Amplified Polymorphic DNA analysis (RAPD) wasused to investigate molecular characteristics of the two variants. Out ofsixty Operon primers that were screened, four primers, OPA 1, OPA 10,OPA 11 and OPK 7 were able to give polymorphism. The fingerprintsgenerated were stable and reproducible on repeated analysis. The DNAfingerprints generated were visually analysed and clustering analysis wascarried out using GelCompar 4.0. The matrix of similarities was based onthe Dice coefficients (S_D) and the cluster analysis was carried outusing the unweighted pair group method using arithmetic averages(UPGMA). DNA analysis showed that two primers (OPA 01, CAGGCCCTTC and OPK 07, AGCGAGCAAG) were able to differentiate the two variants.     

Trichomonas species: homocysteine desulphurase and serine sulphydrase activities

Homocysteine desulphurase (EC 4.4.1.2) and serine sulphydrase (EC 4.2.1.22) activities in various lines of Trichomonas vaginalis, both metronidazole resistant and sensitive, and other trichomonad species were assessed. T. vaginalis contained the highest homocysteine desulphurase and serine sulphydrase activities of all the species. Although the levels of the enzyme activity in T. vaginalis isolates differed, no correlation between the activities and sensitivity to metronidazole was apparent. T. vaginalis homocysteine desulphurase catalysed both the hydrolysis of homocysteine to hydrogen sulphide, ammonia, and 2-oxoacid, and an exchange reaction between homocysteine and 2-mercaptoethanol. Homocysteine desulphurase was detected as a single enzyme band on isoelectric focusing, whereas several isoenzymes of serine sulphydrase were found. There were large differences in serine sulphydrase isoenzyme patterns between T. vaginalis lines and between species. Several isoenzymes were amplified in cells grown with 10(-5) M DL-propargylglycine for 24 hr. T. vaginalis homocysteine desulphurase and serine sulphydrase activities were inhibited by bithionol, hexachlorophene, and dichlorophene. These compounds also inhibited growth in vitro of T. vaginalis at concentrations similar to those that inhibited the enzymes.     

Suppression of monocyte and neutrophil function by recombinant IL-2

Little IS known about the influence of IL-2 on phagocytes. We now describe the effects of human recombinant IL-2 on human neutrophil and monocyte functions related to mobility, phagocytosis, glucose uptake, respiration and degranulation. Neutrophil adherence and hexose monophosphate shunt activities were both suppressed after incubation with IL-2. IL-2 had no effect on neutrophil migration, phagocytosis, deoxyglucose uptake or degranulation, ionocytes demonstrated a greater sensitivity to IL-2 with suppression of monocyte adherence, random and stimulated migration, glucose uptake and hexose monophosphate shunt activity, even after addition of phorbol myristate acetate. Monocyte phagocytosis and degranulation were not affected. All of the effects observed were dose-dependent within a biologically active range for IL-2. These studies suggest that IL-2 may have an important down-regulatory role across a broad range of monocyte functions including movement, deoxyglucose uptake and respiration. However, its role in regulation of neutrophil function is limited to adherence and respiration. IL-2 may be a more versatile cytokine than has previously been appreciated.     

New Dibenzocyclooctadiene Lignans and Phenolics from Kadsura heteroclite with Anti-Inflammatory Activity

A chemical investigation of K. heteroclite led to isolation of two new dibenzocyclooctadienes ( 1 and 2 ) together with 14 known compounds ( 3 – 16 ) by using multiple chromatographic techniques. New compounds ( 1 and 2 ) were obtained and identified by spectroscopic methods (HR-ESI-MS, 1D and 2D NMR, and ECD) as well as by comparison of their experimental data with those reported in the literatures. All the isolates were evaluated for their ability to modulate TNF-α production in lipopolysaccharide (LPS) stimulated RAW264.7 cells. Among them, compound 5 displayed the most inhibition against tumor necrosis factor (TNF)-α production with IC₅₀ value of 6.16±0.14 μM. Whereas, compounds ( 1 , 3 , and 6 ) showed the significant inhibition (IC₅₀ values ranging from 9.41 to 14.54 μM), and compounds ( 2 , 4 , 9 , 10 , 13 , 15 , and 16 ) exhibited moderate inhibition (IC₅₀ values ranging from 19.27 to 40.64 μM) toward TNF-α production, respectively.     

Inhibitory effects of bisbenzylisoquinolines on synthesis of the inflammatory cytokines interleukin-1 and tumour necrosis factor-alpha

Synthesis of IL-1beta and TNFalpha by human monocytesmacrophages was significantly inhibited by eleven bisbenzylisoquinolines and one half-molecule (benzylisoquinoline), with IC(50) values in the muM range. The results indicate that these compounds may have value in the therapy of human diseases where these inflammatory cytokines have a central role in pathogenesis.     

Nitrogen concentrations in a mangrove creek with a large tidal range,Peninsular Malaysia

We report on various species of nitrogen in subsurface water samples taken at the mouth of Sungai Sementa Besar, a creek about 4.5 km long off the Straits of Malacca and draining a mangrove forest on the west coast of Peninsular Malaysia. This tide-dominated watercourse shows a range greater than 4.5 metres from low to high water during springs, only 1.0 m during neaps, and salinities at the mouth of 30 or greater. After heavy rains or when the tides inundate the forest floor, inorganic nitrogen values increase as much as tenfold at the mouth. Particulate and total organic nitrogen also increase at the mouth under these conditions. There were also comparative highs of organic inputs at other times.     

Clinical significance of a high mean corpuscular volume in nonanemic patients.

A prospective study of the clinical significance of macrocytosis (mean corpuscular volume 100 fL or more) was carried out for 9 months in a teaching hospital in 1975. Of the 140 patients with macrocytosis at the time of admission (0l7% of all hospital admissions) 46 (33%) had low activity of serum or erythrocyte folate, or both, and 16 (11%) had low serum vitamin B12 concentrations. Among the 78 patients with normal B12 and folate values the most commonly associated significant clinical conditions were alcoholism or hepatic disease (36 patients), malignant disease or the effects of chemotherapy (25 patients) and chronic obstructive lung disease (10 patients).     

Automated computed tomographic scoring of lung disease in adults with primary ciliary dyskinesia

Background

The present study aimed to develop an automated computed tomography (CT) score based on the CT quantification of high-attenuating lung structures, in order to provide a quantitative assessment of lung structural abnormalities in patients with Primary Ciliary Dyskinesia (PCD).

Methods

Adult (≥18?years) PCD patients who underwent both chest CT and spirometry within a 6-month period were retrospectively included. Commercially available lung segmentation software was used to isolate the lungs from the mediastinum and chest wall and obtain histograms of lung density. CT-density scores were calculated using fixed and adapted thresholds based on various combinations of histogram characteristics, such as mean lung density (MLD), skewness, and standard deviation (SD). Additionally, visual scoring using the Bhalla score was performed by 2 independent radiologists. Correlations between CT scores, forced expiratory volume in 1?s (FEV₁) and forced vital capacity (FVC) were evaluated.

Results

Sixty-two adult patients with PCD were included. Of all histogram characteristics, those showing good positive or negative correlations to both FEV₁ and FVC were SD (R?=???0.63 and???0.67; p?<?0.001) and Skewness (R?=?0.67 and 0.67; p?<?0.001). Among all evaluated thresholds, the CT-density score based on MLD?+?1SD provided the best negative correlation with both FEV₁ (R?=???0.68; p?<?0.001) and FVC (R?=???0.71; p?<?0.001), close to the correlations of the visual score (R?=???0.60; p?<?0.001 for FEV₁ and R?=???0.62; p?<?0.001, for FVC).

Conclusions

Automated CT scoring of lung structural abnormalities lung in primary ciliary dyskinesia is feasible and may prove useful for evaluation of disease severity in the clinic and in clinical trials.

     

A solid-phase synthesis of three aza-, iminoaza- and reduced aza-peptides from the same precursor

Using the Boc-strategy, a step-by-step synthesis on the PAM solid supportof three aza-, iminoaza- and reduced aza-peptide homologues is described.From the same hydrazinocarbonyl peptide-PAM precursor, the coupling ofeither a Boc-amino acid or a Boc-amino aldehyde gives rise to an aza-peptideor an iminoaza-peptide containing theC-CO-NH-N-CO-NH-C orC-CH=N-N-CO-NH-C surrogate of the peptide motif, respectively. In situreduction of the latter by NaBH₃CN leads to a reducedaza-peptide containing theC-CH₂-NH-N-CO-NH-C moiety. The key step synthesis of thehydrazinocarbonyl peptide-PAM precursor is carried out by coupling on thegrowing peptide chain the N-Boc-aza-amino acid chloride obtained by theaction of triphosgene on the corresponding N-Boc-hydrazine. Thesemodifications have been introduced in position 1-2 of the YLGYLEQLLRbenzodiazepine-like decapeptide