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Cassava-enriched diet is not diabetogenic rather it aggravates diabetes in rats.

Chronic intake of cassava has been thought to play a role in the pathogenesis of diabetes. We investigated the effects of dietary cassava (Manihot esculenta), which naturally contains cyanogenic glycosides, in the progression of diabetes mellitus in rats. Diabetes was induced by five mild doses of streptozotocin, in male Wistar rats which were fed a standard or cyanide-free cassava (CFC) diet containing or not containing exogenous cyanide with or without methionine. Methionine was employed to counterbalance the toxic effects of cyanide. During diabetes progression, we determined glycaemia and antioxidant status, by measuring vitamin C levels and activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione reductase (GSSG-Red). Feeding CFC diet did not induce diabetes in control rats; rather this diet, in diabetic animals, aggravated hyperglycaemia the severity of which was increased in these animals fed CFC diet, supplemented with cyanide. Addition of methionine curtailed the toxic effects of cyanide supplementation in CFC diet-fed diabetic animals. In standard diet-fed animals, the activities of SOD, GSH-Px and GSSG-Red were lower in diabetic rats than control rats. Interestingly, all of the CFC diets with or without cyanide or methionine, increased vitamin C levels and antioxidant enzyme activities in both control and diabetic animals. However, supplementing cyanide to CFC diet (without methionine) curtailed SOD and GSH-Px activities in diabetic rats. Our study shows that cassava diet containing cyanide is 'diabetes-aggravating'.

Animals↗

Electrophysiological effects of S 16257, a novel sino-atrial node modulator, on rabbit and guinea-pig cardiac preparations: comparison with UL-FS 49.

1. S 16257 is a new bradycardic agent. Its electropharmacological profile has been compared to that of the known bradycardic compound UL-FS 49 (Zatebradine). Intracellular recordings of action potentials (APs) were performed with conventional glass microelectrodes. 2. In the rabbit isolated sino-atrial node (SAN) tissue, S 16257 and UL-FS 49 (1 microM, 3 microM and 10 microM) were equipotent in slowing spontaneous APs firing predominantly by decreasing the rate of diastolic depolarization (at 3 microM, -23.8 +/- 3.9% and -27.9 +/- 2.6%, respectively). For the two compounds a maximal effect was obtained at 3 microM. In these preparations, action potential duration at 50% of total repolarization (APD50) was more affected by UL-FS 49 than S 16257 at any concentration tested (at 3 microM, +8.9 +/- 2.9% and +29.1 +/- 3.7% for S 16257 and UL-FS 49, respectively; P < or = 0.01). 3. To estimate the direct effects on AP duration, driven cardiac preparations were exposed to these agents. In guinea-pig papillary muscles, paced at a frequency of 1 Hz, increasing concentrations of S 16257 or UL-FS 49 (0.1 to 10 microM, 30 min exposure for each concentration) slightly prolonged AP repolarization. This prolongation was more marked for UL-FS 49 (at 1 microM, +6.1 +/- 0.6% and +11.2 +/- 1.3% elevation of APD50, for S 16257 and UL-FS 49, respectively). 4. Application of UL-FS 49 (3 microM) to rabbit Purkinje fibres, triggered at a frequency of 0.25 Hz, induced a marked prolongation of APD50 and APD90 (+149.4 +/- 51.2% and +86.0 +/- 15.4%, respectively). S 16257 (3 MicroM) induced only a weak prolongation of AP (+ 14.1 +/- 5.0% and + 14.8 +/- 3.3% for APD50 and APD90, respectively) significantly smaller than in the case of UL-FS 49.5. These results show that S 16257 slows the rate of spontaneous AP firing in isolated SAN mainly by a reduction of the diastolic depolarization of the cells, which suggests an inhibition of the pace-maker current (If). S 16257 and UL-FS 49 are equipotent in their bradycardic effect but S 16257 is more specific as it induces less increase in myocardial repolarization time.

Action Potentials↗

Poikiloderma of Theresa Kindler: report of a case with ultrastructural study, and review of the literature.

Kindler's syndrome occurred in a 13-year-old boy with parental consanguinity. The patient had acral congenital blistering and photosensitivity, both regressive, at 12 years of age, together with diffuse progressive poikiloderma, marked cutaneous atrophy, mild hyperkeratosis of the palms, gingival hypertrophy and fragility, and anal stenosis. The ultrastructural study of bullae induced by rubbing showed clefts in three levels of the dermoepidermal junction zone. A review of 14 cases in the literature consistent with Kindler's syndrome showed this to be a definite clinical entity among the other bullous hereditary poikilodermas. In two cases, ultrastructural studies showed intraepidermal, junctional, and dermal cleavage. This syndrome must be differentiated from congenital epidermolysis bullosa, Weary's syndrome, and the other bullous hereditary poikilodermas.

Adolescent↗

Atopic dermatitis: recent therapeutic advances.

New treatments were recently proposed for the management of severe atopic dermatitis (AD). They all act on some component of the immune reaction. Oral cyclosporine reduces the number of CD4+ cells, the secretion of interleukins, and the function of Langerhans cells. Although the action of oral cyclosporine at moderately high dosages is regular and rapid, the risk of serious side effects and the reappearance of progressive disease after stopping treatment limits the use of this drug in AD. Thymic hormone extracts in patients with severe AD affect the deficit of cellular immunity. gamma-Interferon inhibits IgE synthesis induced by interleukin-4, increases expression of Fc gamma receptors, and increases superoxide production by circulating monocytes. More recently, two other treatments were published: complexes of allergen and specific antibodies to Dermatophagoides pteronyssinus, and interleukin-2. All of these modalities have only a transitory effect, but they can help to modify a flare of severe AD.

Adult↗

The decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage.

BACKGROUND: Postpartum hemorrhage (PPH) is a major source of maternal morbidity. OBJECTIVES: This study's objective was to determine whether changes in hemostasis markers during the course of PPH are predictive of its severity. PATIENTS AND METHODS: We enrolled 128 women with PPH requiring uterotonic prostaglandin E2 (sulprostone) infusion. Two groups were defined (severe and non-severe PPH) according to the outcome during the first 24 hours. According to our criteria, 50 of the 128 women had severe PPH. Serial coagulation tests were performed at enrollment (H0), and 1, 2, 4 and 24 hours thereafter. RESULTS: At H0, and through H4, women with severe PPH had significantly lower fibrinogen, factor V, antithrombin activity, protein C antigen, prolonged prothrombin time, and higher D-dimer and TAT complexes than women with non-severe PPH. In multivariate analysis, from H0 to H4, fibrinogen was the only marker associated with the occurrence of severe PPH. At H0, the risk for severe PPH was 2.63-fold higher for each 1 gL(-1) decrease of fibrinogen. The negative predictive value of a fibrinogen concentration >4 gL(-1) was 79% and the positive predictive value of a concentration <or=2 gL(-1) was 100%. CONCLUSION: These findings indicate that a simple fibrinogen measurement can anticipate the risk of severe bleeding in PPH.

Adult↗

Serum lecithin: cholesterol acyltransferase activity and HDL2 and HDL3 composition in small for gestational age newborns.

The aim of this study was to determine serum lecithin: cholesterol acyltransferase (LCAT) activity in parallel with HDL2 and HDL3 composition in cord sera of small for gestational age (SGA) newborns, and to compare them with those obtained from appropriate for gestational age (AGA) newborns. LCAT activity was assayed by conversion of [3H]cholesterol to labelled cholesteryl ester. HDL2 and HDL3 were separated by ultracentrifugation. Serum cholesteryl ester, apolipoprotein (apo) A-I concentrations and LCAT activity were significantly lower (-47%, -18% and -56%, respectively), whereas serum triglyceride amounts were twofold higher in SGA newborns than in AGA newborns. In SGA newborns, HDL2 and HDL3 levels were low, and HDL3 and HDL2 phospholipid and HDL2-cholesteryl ester contents were diminished. HDL3-apo A-I, A-II, C-III and E values were lower in SGA newborns. In HDL2, apo A-I, A-II and E concentrations were decreased. Therefore, in SGA newborns, the reduced LCAT activity was associated with quantitative and qualitative changes in HDL2 and HDL3 particles.

Apolipoprotein A-I↗

Syndecan-4 is a signaling molecule for stromal cell-derived factor-1 (SDF-1)/ CXCL12.

Stromal cell-derived factor-1 (SDF-1)/CXCL12, the ligand for CXCR4, induces signal transduction. We previously showed that CXCL12 binds to high- and low-affinity sites expressed by primary cells and cell lines, and forms complexes with CXCR4 as expected and also with a proteoglycan, syndecan-4, but does not form complexes with syndecan-1, syndecan-2, CD44 or beta-glycan. We also demonstrated the occurrence of a CXCL12-independent heteromeric complex between CXCR4 and syndecan-4. However, our data ruled out the glycosaminoglycan-dependent binding of CXCL12 to HeLa cells facilitating the binding of this chemokine to CXCR4. Here, we demonstrate that CXCL12 directly binds to syndecan-4 in a glycosaminoglycan-dependent manner. We show that upon stimulation of HeLa cells by CXCL12, CXCR4 becomes tyrosine phosphorylated as expected, while syndecan-4 (but not syndecan-1, syndecan-2 or beta-glycan) also undergoes such tyrosine phosphorylation. Moreover, tyrosine-phosphorylated syndecan-4 from CXCL12-stimulated HeLa cells physically coassociates with tyrosine phosphorylated CXCR4. Pretreatment of the cells with heparitinases I and III prevented the tyrosine phosphorylation of syndecan-4, which suggests that the heparan sulfate-dependent binding of SDF-1 to this proteoglycan is involved. Finally, by reducing syndecan-4 expression using RNA interference or by pretreating the cells with heparitinase I and III mixture, we suggest the involvement of syndecan-4 and heparan sulfate in p44/p42 mitogen-activated protein kinase and Jun N-terminal/stress-activated protein kinase activation by action of CXCL12 on HeLa cells. However, these treatments did not modify the calcium mobilization induced by CXCL12 in these cells. Therefore, syndecan-4 behaves as a CXCL12 receptor, selectively involved in some transduction pathways induced by SDF-1, and heparan sulfate plays a role in these events.

Calcium↗

Spin-lock magnetic resonance imaging of muscle in patients with autosomal recessive limb girdle muscular dystrophy.

Spin-lock imaging is a new magnetic resonance imaging (MRI) technique used to reflect the microstructural integrity of muscle. The purpose of this study was to characterize spin-lock contrast (SLC) of calf muscles in limb girdle muscular dystrophy (LGMD). The calf muscles of 5 patients with LGMD and 10 healthy volunteers were imaged with an off-resonance magnetic resonance (MR) spin-lock suppression pulse. Spin-lock suppression ratios were calculated for anterior tibialis, posterior tibialis, soleus, and gastrocnemius muscles. Clinical assessments of muscle strength were compared to the spin-lock suppression ratios in the LGMD group. Strong SLC was observed in healthy muscles, with mean (+/- SD) suppression ratios ranging from 51.2% (+/- 3.6%) to 56.3% (+/- 1.3%). In diseased muscle, spin-lock signal suppression was reduced by 8%-70%, demonstrating an inverse correlation between symptom duration and suppression ratios. Spin-lock contrast in the patients with LGMD, as a reflection of tissue integrity, was best preserved in posterior tibialis, anterior tibialis, soleus, and gastrocnemius muscles in descending order. Clinical assessments did a poorer job of differentiating than SLC did and were in poor agreement with spin-lock suppression ratios. Spin-lock MRI can quantify microstructural changes in LGMD and appears to provide information not obtainable from clinical evaluations. This suggests that this noninvasive technique may be useful in evaluating the extent, progression, and response to therapy of LGMD.

Adolescent↗

Zinc is both an intracellular and extracellular regulator of KATP channel function.

Extracellular Zn(2+) has been identified as an activator of pancreatic K(ATP) channels. We further examined the action of Zn(2+) on recombinant K(ATP) channels formed with the inward rectifier K(+) channel subunit Kir6.2 associated with either the pancreatic/neuronal sulphonylurea receptor 1 (SUR1) subunit or the cardiac SUR2A subunit. Zn(2+), applied at either the extracellular or intracellular side of the membrane appeared as a potent, reversible activator of K(ATP) channels. External Zn(2+), at micromolar concentrations, activated SUR1/Kir6.2 but induced a small inhibition of SUR2A/Kir6.2 channels. Cytosolic Zn(2+) dose-dependently stimulated both SUR1/Kir6.2 and SUR2A/Kir6.2 channels, with half-maximal effects at 1.8 and 60 microm, respectively, but it did not affect the Kir6.2 subunit expressed alone. These observations point to an action of both external and internal Zn(2+) on the SUR subunit. Effects of internal Zn(2+) were not due to Zn(2+) leaking out, since they were unaffected by the presence of a Zn(2+) chelator on the external side. Similarly, internal chelators did not affect activation by external Zn(2+). Therefore, Zn(2+) is an endogenous K(ATP) channel opener being active on both sides of the membrane, with potentially distinct sites of action located on the SUR subunit. These findings uncover a novel regulatory pathway targeting K(ATP) channels, and suggest a new role for Zn(2+) as an intracellular signalling molecule.

Adenosine Triphosphate↗

Segregation in DNA solutions induced by electric fields.

DNA solutions subjected to an electric field exhibit an instability that leads to DNA segregation in aggregates tilted with regard to the field. With the use of epifluorescence videomicroscopy, the evolution of DNA patterns in capillaries as a function of DNA concentration, DNA size, field strength, and field frequency was studied. The field threshold for segregation was decreased when the frequency was lowered or when the DNA molecular weight or concentration was increased. Aggregation is attributed to an electrohydrodynamic instability triggered by the dipole-dipole interaction. This phenomenon explains the failure of earlier attempts to separate large DNA in capillaries.

DNA↗

Characterization of colony morphology variants isolated from Pseudomonas aeruginosa biofilms.

In this study, we report the isolation of small, rough, strongly cohesive colony morphology variants from aging Pseudomonas aeruginosa PAO1 biofilms. Similar to many of the P. aeruginosa colony morphology variants previously described in the literature, these variants autoaggregate in liquid culture and hyperadhere to solid surfaces. They also exhibit increased hydrophobicity and reduced motility compared to the wild-type parent strain. Despite the similarities in appearance of our colony morphology variant isolates on solid medium, the isolates showed a range of responses in various phenotypic assays. These variants form biofilms with significant three-dimensional structure and more biomass than the wild-type parent. To further explore the nature of the variants, their transcriptional profiles were evaluated. The variants generally showed increased expression of the psl and pel loci, which have been previously implicated in the adherence of P. aeruginosa to solid surfaces. When a mutation in the psl locus was introduced into a colony morphology variant, the colony morphology was only partially affected, but hyperadherence and autoaggregation were lost. Finally, similar colony morphology variants were found in isolates from cystic fibrosis patients. These variants displayed many of the same characteristics as the laboratory variants, suggesting a link between laboratory and cystic fibrosis biofilms.

Bacterial Adhesion↗

Cra-dependent transcriptional activation of the icd gene of Escherichia coli.

The icd gene of Escherichia coli, encoding isocitrate dehydrogenase, was shown to be expressed from two different promoters: the previously identified icd P1 and a newly detected second promoter, icd P2, whose expression is positively regulated by the catabolite repressor-activator protein Cra, formerly called FruR. In each case, we determined the mRNA start site by primer extension analysis of in vivo transcripts and examined the interaction of the icd control region with either RNA polymerase or Cra. We observed that (i) the Cra factor binds to and activates transcription from a site centered at position -76.5 within the icd P2 promoter region and (ii) three particular mutations in the C-terminal end of the alpha subunit of RNA polymerase (L262A, R265A, and N268A) considerably diminish transcription initiating from the icd P2 promoter, as shown by in vitro experiments performed in the presence of mutant RNA polymerases carrying Ala substitutions.

Amino Acid Substitution↗

Characterization of the two Mycobacterium tuberculosis recA promoters.

The recA gene of Mycobacterium tuberculosis is unusual in that it is expressed from two promoters, one of which, P1, is DNA damage inducible independently of LexA and RecA, while the other, P2, is regulated by LexA in the classical way (E. O. Davis, B. Springer, K. K. Gopaul, K. G. Papavinasasundaram, P. Sander, and E. C. Böttger, Mol. Microbiol. 46:791-800, 2002). In this study we characterized these two promoters in more detail. Firstly, we localized the promoter elements for each of the promoters, and in so doing we identified a mutation in each promoter which eliminates promoter activity. Interestingly, a motif with similarity to Escherichia coli sigma(70) -35 elements but located much closer to the -10 element is important for optimal expression of P1, whereas the sequence at the -35 location is not. Secondly, we found that the sequences flanking the promoters can have a profound effect on the expression level directed by each of the promoters. Finally, we examined the contribution of each of the promoters to recA expression and compared their kinetics of induction following DNA damage.

Bacterial Proteins↗

Epidemiology of adult Still's disease: estimate of the incidence by a retrospective study in west France.

OBJECTIVES: To estimate the incidence of adult Still's disease (ASD) and to specify, if possible, associated factors. METHODS: A retrospective study of the populations of the Brittany and Loire regions in west France was made from 1 January 1982 to 31 December 1991. All internal medicine and rheumatology practitioners of these regions were consulted. RESULTS: Sixty-two (62) cases were reported (93% response). The disease incidence calculated over five years was 0.16 per 100,000 inhabitants in the study population. There was no sex bias (sex ratio 1.06 in ASD v 1.05 in the overall population. The mean age of the study population was 36 years, with two peaks of distribution at 15-25 and 36-45 years. A history of allergy was present in 23% of patients (n = 14). In two patients, it was possible to correlate an environmental allergen to exacerbation of ASD. CONCLUSION: The yearly incidence of ASD was estimated to be 0.16 per 100,000 inhabitants. However, it was not possible to incriminate any infectious, toxic, or genetic factors in exacerbation of the disease.

Adolescent↗

Antiperinuclear factors are present in polyarthritis before ACR criteria for rheumatoid arthritis are fulfilled.

OBJECTIVE: To show that antiperinuclear factor (APF) may be useful for the diagnosis of rheumatoid arthritis at a time when the American College of Rheumatology (ACR) criteria are not yet fulfilled. METHODS: Testing for APF-IgG (1:100 threshold) and rheumatoid factors (RF) was done in 60 patients with polyarthritis of recent onset during a three year follow up. RESULTS: At the end of the study, 21/40 rheumatoid arthritis were positive for RF and 31/40 for APF, including 18/40 cases (45%) in which ACR criteria were not yet fulfilled. CONCLUSIONS: APF are useful in the diagnosis of early rheumatoid arthritis.

Antibodies, Antinuclear↗

Experimental ocular siderosis after extrabulbar administration of iron.

The authors studied the penetration of iron administered extrabulbarly into the ocular tissues of rabbits. It was found that iron passes from the orbit into the eyeball and accumulates in considerable quantities in the sclera, choroid, retina, ciliary body, and even in the vitreous and corneal epithelium. However, light microscopy failed to show any damage to the ocular tissues. The mechanism by which iron penetrates into the eyeball is discussed, and comparison is made between changes in the tissues, which characterise siderosis produced by an intrabulbar iron foreign body, and those in which an extrabulbar foreign body is involved.

Animals↗