Evidence against the "spare" receptor nature of alpha 2-adrenoceptors in hamster white fat cells

After having established the alpha 2-adrenoceptor nature of the binding sites specifically labeled by the alpha 2-agonist [3H] UK 14304 in hamster adipocytes, two different approaches have been used to determine whether these alpha 2-adrenoceptors were "spare receptors". The first one, consisted to block irreversibly fractions of the receptor population by various concentrations of the alpha 2-antagonist benextramine and determine the relationship between the residual receptor occupancy by UK 14304 and the corresponding magnitude of the cellular inhibitory cyclic AMP response to the alpha 2-adrenergic component of epinephrine under conditions avoiding cyclic AMP breakdown. The second approach was a detailed comparison between alpha 2-receptor occupancy by [3H] UK 14304 and the cyclic AMP inhibitory dose-response curve to this agonist in cells incubated also under conditions avoiding cyclic AMP breakdown. These two experimental approaches clearly showed that the alpha 2-adrenoceptor of hamster adipocytes are not "spare receptors".     

First Evidence of Simultaneous Circulation of Three Different Dengue Virus Serotypes in Africa

Gabon, in Central Africa, was affected for the first time in 2007 and then in 2010 by simultaneous outbreaks of chikungunya and Dengue serotype 2 (DENV-2) viruses. Through the national surveillance of dengue-like syndromes between 2007 and 2010, we observed continuous circulation of DENV-2 in a southward movement. This rapid spread of DENV-2 was associated with the emergence of DENV-1 in 2007 and DENV-3 in 2010. Interestingly, we detected six DENV-2 infected patients with hemorrhagic signs during the second outbreak in 2010. Although these cases do not meet all standard WHO criteria for severe Dengue with hemorrhage (formerly DHF), this is the first report of several dengue fever cases associated with hemorrhagic signs during a simultaneous circulation of different DENV serotypes in Africa. Together, these findings suggest that DENV is becoming more widely established on this continent and that DHF will likely become a serious public-health problem in the near future.     

Caenorhabditis elegans S-adenosylmethionine decarboxylase is highly stimulated by putrescine but exhibits a low specificity for activator binding

S-Adenosylmethionine decarboxylase (AdoMetDC) is a key enzyme of the polyamine synthetic pathway providing decarboxylated S-adenosylmethionine for the formation of spermidine and spermine, respectively. The catalytic activity of the AdoMetDC from the free-living nematode Caenorhabditis elegans highly depends on the presence of an activator molecule. Putrescine, a well-known stimulator of mammalian AdoMetDC activity, enhances the catalytic activity of the nematode enzyme 350-fold. Putrescine stimulation is discussed as a regulatory mechanism to relate putrescine abundance with the synthesis of spermidine and spermine. In contrast to any other known AdoMetDC, spermidine and spermine also represent significant activators of the nematode enzyme. However, the biological significance of the observed stimulation by these higher polyamines is unclear. Although C. elegans AdoMetDC exhibits a low specificity toward activator molecules, the amino acid residues that were shown to be involved in putrescine binding of the human enzyme are conserved in the nematode enzyme. Exchanging these residues by site-directed mutagenesis indicates that at least three residues, Thr192, Glu194 and Glu274, most likely contribute to activator binding in the C. elegans AdoMetDC. Interestingly, the mutant Glu194Gln exhibits a 100-fold enhanced basal activity in the absence of any stimulator, suggesting that this mutant protein mimics the conformational change usually induced by activator molecules. Furthermore, site-directed mutagenesis revealed that at least Glu33, Ser83, Arg91 and Lys95 are involved in posttranslational processing of C. elegans AdoMetDC.     

Methyl Jasmonate Increases the Tropane Alkaloid Scopolamine and Reduces Natural Herbivory in Brugmansia suaveolens: Is Scopolamine Responsible for Plant Resistance?

The tropane alkaloid (TA) scopolamine is suggested to protect Brugmansia suaveolens (Solanaceae) against herbivorous insects. To test this prediction in a natural environment, scopolamine was induced by methyl jasmonate (MJ) in potted plants which were left 10?days in the field. MJ-treated plants increased their scopolamine concentration in leaves and herbivory decreased. These findings suggest a cause?Ceffect relationship. However, experiments in laboratory showed that scopolamine affect differently the performance of the specialist larvae of the ithomiine butterfly Placidina euryanassa (C. Felder & R. Felder) and the generalist fall armyworm Spodoptera frugiperda (J. E. Smith): the specialist that sequester this TA from B. suaveolens leaves was not negatively affected, but the generalist was. Therefore, scopolamine probably acts only against insects that are not adapted to TAs. Other compounds that are MJ elicited may also play a role in plant resistance against herbivory by generalist and specialist insects, and deserve future investigations.     

Cyanotoxins in small artificial dams in Kenya utilised for cage fish farming – a threat to local people?

Nine small artificial dams located in different climatic regions of Kenya were studied. The local communities use the stored water for various purposes, such as irrigation, domestic use, watering of livestock and cage fish farming. Such intense use is commonly accompanied by eutrophication, including fast growth of cyanobacteria, which at times produce cyanotoxins threatening human and animal life. We studied the pelagic community, analysed abiotic variables and identified microcystins by means of high performance liquid chromatography and ELISA kits at monthly intervals over a period of one year. Mass spectrometry (MALDI-TOF MS) was used to identify structural variants of microcystins by their protonated masses (M + H). Three dams contained microcystins, with the highly toxic Microcystin-LR being identified as the most prominent substance. Cell content of the toxin varied from 7.2 to 686.7 fg cell^?1. Basic limnological variables that indicate the probability of toxin presence were also recorded. Non-parametric Mann–Whitney U-test revealed significant differences in soluble reactive phosphorous, nitrate-N, water depth, total hardness and post-Nauplii stages sampled between toxin-producing and non-toxin-producing dams. Although most of the samples did not contain high amounts of cyanobacteria, the cyanotoxin-problem was evident, suggesting the need for regular cyanotoxin monitoring programs.     

Where Do We Go from Here? Prevalence of Trachoma Three Years after Stopping Mass Distribution of Antibiotics in the Regions of Kayes and Koulikoro,Mali

Objectives

A national survey in 1997 demonstrated that trachoma was endemic in Mali. Interventions to control trachoma including mass drug administration (MDA) with azithromycin were launched in the regions of Kayes and Koulikoro in 2003. MDA was discontinued after three annual rounds in 2006, and an impact survey conducted. We resurveyed all districts in Kayes and Koulikoro in 2009 to reassess trachoma prevalence and determine intervention objectives for the future. In this paper we present findings from both the 2006 and 2009 surveys.

Methods

Population-based cluster surveys were conducted in each of the nine districts in Koulikoro in 2006 and 2009, whilst in Kayes, four of seven districts in 2006 and all seven districts in 2009 were surveyed. Household members present were examined for clinical signs of trachoma.

Results

Overall, 29,179 persons from 2,528 compounds, in 260 clusters were examined in 2006 and 32,918 from 7,533 households in 320 clusters in 2009. The prevalence of TF in children aged 1–9 years in Kayes and Koulikoro was 3.9% (95%CI 2.9–5.0%, range by district 1.2–5.4%) and 2.7% (95%CI 2.3–3.1%, range by district 0.1–5.0%) respectively in 2006. In 2009 TF prevalence was 7.26% (95%CI 6.2–8.2%, range by district 2.5–15.4%) in Kayes and 8.19% (95%CI 7.3–9.1%, range by district 1.7–17.2%) in Koulikoro among children of the same age group. TT in adults 15 years of age and older was 2.37% (95%CI 1.66–3.07%, range by district 0.30–3.54%) in 2006 and 1.37% (95%CI 1.02–1.72%, range by district 0.37–1.87%) in 2009 in Kayes and 1.75% (95%CI 1.31–2.23%, range by district 1.06–2.49%) in 2006 and 1.08% (95%CI 0.86–1.30%, range by district 0.34–1.78%) in 2009 in Koulikoro.

Conclusions

Using WHO guidelines for decision making, four districts, Bafoulabe in Kayes Region; and Banamba, Kolokani and Koulikoro in Koulikoro Region, still meet criteria for district-wide implementation of the full SAFE strategy as TF in children exceeds 10%. A community-by-community approach to trachoma control may now be required in the other twelve districts. Trichiasis surgery provision remains a need in all districts and should be enhanced in six districts in Kayes and five in Koulikoro where the prevalence exceeded 1.0% in adults. Since 1997 great progress has been observed in the fight against blinding trachoma; however, greater effort is required to meet the elimination target of 2015.     

Aflatoxicosis in rabbits: Effectiveness of Egyptian raw bentonite in prevention or diminution the detrimental effects of naturally aflatoxin contaminated diets

Thirty five females and 15 males of New Zealand White mature rabbits about 6 months of age, were assigned to 1–5 dietary treatments (7 does+3 bucks for each): uncontaminated control diet, naturally aflatoxin contaminated diet without or with 1,2 and 3% bentonite. Rabbit fed with the aflatoxin-diet had a decreased (P<0.01 or 0.05) physical semen characteristics of bucks and a reproductive performance traits of does. The values of conception rate (%), gestation length (days), litter size (n) and litter weights (g) at birth and viability (%) of litters of doe rabbits, fed with the aflatoxin-diet, recorded, respectively: 64.5; 31.0; 4.4; 275.0 and 57.1 versus 85.6; 30.3; 7.9; 508.0; and 100 for those fed with the uncontaminated diet. Addition of bentonite to the aflatoxin contaminated diet improved in general the physical semen characteristics of buck and reproductive performance traits of doe rabbits. The results of the study demonstrate that adding 1% of Egyptian raw bentonite to the naturally aflatoxin contaminated rabbit diets can provide an effective, cheap and safe practical technique for preventing the aflatoxicosis in mature rabbits.     

Dracunculiasis (guinea worm disease): eradication without a drug or a vaccine

Dracunculiasis, commonly known as guinea worm disease, is a nematode infection transmitted to humans exclusively via contaminated drinking water. The disease prevails in the most deprived areas of the world. No vaccine or medicine is available against the disease: eradication is being achieved by implementing preventive measures. These include behavioural change in patients and communities—such as self-reporting suspected cases to health workers or volunteers, filtering drinking water and accessing water from improved sources and preventing infected individuals from wading or swimming in drinking-water sources—supplemented by active surveillance and case containment, vector control and provision of improved water sources. Efforts to eradicate dracunculiasis began in the early 1980s. By the end of 2012, the disease had reached its lowest levels ever. This paper reviews the progress made in eradicating dracunculiasis since the eradication campaign began, the factors influencing progress and the difficulties in controlling the pathogen that requires behavioural change, especially when the threat becomes rare. The challenges of intensifying surveillance are discussed, particularly in insecure areas containing the last foci of the disease. It also summarizes the broader benefits uniquely linked to interventions against dracunculiasis.     

Glucose administration before exercise modulates catecholaminergic responses in glycogen-depleted subjects

Gozal, David, Patrice Thiriet, Jean Marie Cottet-Emard,Dieudonné Wouassi, Emmanuel Bitanga, André Geyssant, JeanMarc Pequignot, and Marcel Sagnol. Glucose administration before exercise modulates catecholaminergic responses in glycogen-depleted subjects. J. Appl. Physiol. 82(1):248-256, 1997.In glycogen-depleted subjects (GD) a nonlinearincrease in epinephrine (Epi) and norepinephrine (NE) parallels bloodlactate (La) during graded exercise. The effect of glucose(Glc) supplementation and route of administration on theserelationships was studied in 26 GD athletes who were randomly assignedto receive 1.3 g/kg Glc by slow intravenous infusion (IV;n = 9), oral administration (PO;n = 9), or artificially sweetenedplacebo in 1 liter of water (Asp; n = 8) in the 2 h preceding a graded maximal exercise. Performance and Lawere similar among the three groups in normal glycogen (NG) or GDconditions. However, slightly improved performances were observed in GDcompared with NG and were associated with a shift to the right in Lacurves. Blood Glc concentrations were higher in IV and PO beforeexercise, but they rapidly decreased to lowest levels in IV, graduallydecreased over time in PO, and remained stable in Asp or NG. Insulinconcentrations were highest in IV and lowest in Asp and NG at onset ofexercise, rapidly decreasing in IV and PO although remaining at higherlevels than in Asp or NG. In contrast, higher serum levels of freefatty acids were measured during exercise in Asp with no significant differences in glucagon or glycerol among the three groups. Free andsulfated NE increases were smaller in IV than in PO and Asp onexhaustion. In contrast, free and conjugated Epi were most increased inIV, with smallest increases in Asp. Dopamine levels were most increasedin IV at exhaustion. We conclude that the changes of Epi and NEconcentrations, associated with the activation of glucoregulatorymechanisms, including hyperinsulinemia, display different magnitude andtime courses during exercise in GD subjects who receive oral vs.intravenous load of Glc before exercise. We speculate that themagnitude of insulin surge after acutely increased Glc before exercisein GD subjects may exert dissociative effects on adrenal-dependentglycogenolysis and on sympathetic responses.