Efficacy of a collagen-based dressing in an animal model of delayed wound healing.

OBJECTIVE: The aim of this study was to evaluate in vitro and in vivo the efficacy of GBT013, a collagen-based dressing, for the treatment of chronic wounds, in a db/db mouse model of diabetes. METHOD: Macroscopic and histologic analyses of db/db mice wound healing with GBT013 or saline gauze were assessed. The mRNA expression and the proliferation of dermal fibroblast were investigated. Matrix metalloproteinases (MMP)-2 and MMP-9 activities were quantified. RESULTS: In db/db mice, GBT013 improves wound epithelialisation when compared with saline gauze. Histological analysis of scar tissue also shows an enhancement of remodelling associated with no sign of acute inflammation. In addition, GBT013 significantly decreases interleukin (IL)-6 and IL-8, significantly increases tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 fibroblast mRNA expression and significantly reduces in vitro MMP-2 and MMP-9 enzymatic activities. Moreover, GBT013 allows cell growth inside the matrix and stimulates proliferation of human dermal fibroblast. CONCLUSION: By contributing to restore MMPs/TIMPs balance, GBT013 may function in all key stages of wound healing, such as inflammation, proliferation and tissue remodelling, and ultimately may provide a favourable environment for skin repair. DECLARATION OF INTEREST: This work was supported by Genbiotech, the R&D subsidiary of Laboratoires Genévrier, a pharmaceutical company.

Electrical and rheological properties of sewage sludge--Impact of the solid content.

Sludge treatment is a multistep process during which sludge is mixed, pumped, thickened and dewatered. The total solid content (TSC) increases from a few grams to more than a hundred grams per liter and as underlined by the existing literature, rheological characteristics are key criteria for sludge management. However, these characteristics remain difficult to be determined in-situ and professionals are looking for alternative techniques to evaluate them. In that context, the potential of electrical measurements has been highlighted (Dieudé-Fauvel et al., 2009, 2014). This paper investigates the additional benefits of correlating both rheological and electrical properties for sludge characterization within the range of 1-23%TSC. On a rheological point of view, results are consistent with previous literature. In parallel, electrical impedance spectroscopy allowed us to define an equivalent electrical circuit to model the sludge electrical signature. Results highlight that the circuit parameters follow two regimes according to the range of solid content, similarly to rheological properties. This work opens new insights about sludge characterization and treatment monitoring.

Relationship between electrical and rheological properties of sewage sludge - Impact of temperature.

Rheological properties are key criteria for sewage sludge management but are difficult to determine in situ. Because the literature often links rheological characteristics to surface charges of particles that interact, the underlying electrostatic interactions could be key characteristics explaining the rheological behavior of sludge. This paper analyzed the impact of temperature on both rheological and electrical properties. Both liquid and solid properties appear to be related to electrical impedance spectroscopy measurements because they obey the same relationships with the same activation energies. Infinite viscosity follows an Arrhenius law with temperature, whereas the storage modulus shows VTF (Vogel-Tamman-Fulcher) behavior. Sludge electrical behavior can be modeled by an equivalent 2-branch parallel circuit whose respective impedances follow Arrhenius and VTF relationships. More interestingly, resistors are proportional to (dissipative) viscous characteristics, whereas capacitances are proportional to the (storage) elastic modulus. These similarities and relationships underlie the same interactions that seem to be involved in both rheological and electrical properties. These interdependences are quite logical but open new insights into sludge characterization.

Insulin signalling downstream of protein kinase B is potentiated by 5'AMP-activated protein kinase in rat hearts in vivo.

AIMS/HYPOTHESIS: 5'AMP-activated protein kinase (AMPK) and insulin stimulate glucose transport in heart and muscle. AMPK acts in an additive manner with insulin to increase glucose uptake, thereby suggesting that AMPK activation may be a useful strategy for ameliorating glucose uptake, especially in cases of insulin resistance. In order to characterise interactions between the insulin- and AMPK-signalling pathways, we investigated the effects of AMPK activation on insulin signalling in the rat heart in vivo. METHODS: Male rats (350-400 g) were injected with 1 g/kg 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) or 250 mg/kg metformin in order to activate AMPK. Rats were administered insulin 30 min later and after another 30 min their hearts were removed. The activities and phosphorylation levels of components of the insulin-signalling pathway were subsequently analysed in individual rat hearts. RESULTS: AICAR and metformin administration activated AMPK and enhanced insulin signalling downstream of protein kinase B in rat hearts in vivo. Insulin-induced phosphorylation of glycogen synthase kinase 3 (GSK3) beta, p70 S6 kinase (p70S6K)(Thr389) and IRS1(Ser636/639) were significantly increased following AMPK activation. To the best of our knowledge, this is the first report of heightened insulin responses of GSK3beta and p70S6K following AMPK activation. In addition, we found that AMPK inhibits insulin stimulation of IRS1-associated phosphatidylinositol 3-kinase activity, and that AMPK activates atypical protein kinase C and extracellular signal-regulated kinase in the heart. CONCLUSIONS/INTERPRETATIONS: Our data are indicative of differential effects of AMPK on the activation of components in the cardiac insulin-signalling pathway. These intriguing observations are critical for characterisation of the crosstalk between AMPK and insulin signalling.

Prevalence of allergy to Hymenoptera stings.

In this study, we evaluated the prevalence of systemic reactions to hymenoptera stings in an adult general population, 20-60 years old. The protocol included a standardized questionnaire, skin tests to venom in subjects reporting a history of systemic reaction, and in subjects reporting a history of severe local and systemic reactions, as well as in a control group, a radioallergosorbent test (RAST) to hymenoptera venoms. According to the questionnaire, 1.2% of the study population had a history of systemic reactions. Only 0.85% had both such a history and a positive skin test to venoms. RASTs were positive, for at least one venom, in 57% of subjects with a history of systemic reaction, 15.8% of subjects with a history of severe local reactions, and 6.0% of the control group. In conclusion, this study shows that systemic reactions are not uncommon in the general population. RASTs tests are not sensitive or specific enough to be considered, per se, for indications of allergy to venoms.

Comparison between modified skin prick test with standardized allergen extracts and Phazet.

Skin prick tests (SPTs) represent one of the most common techniques of skin testing and are of great value, especially when standardized extracts are used. Phazet is a puncture test involving needles coated with standardized allergens. Phazet and SPTs have been compared in 130 subjects tested with six standardized allergen extracts: orchard-grass, olive, and mugwort pollens, cat dander, Dermatophagoides pteronyssinus, and Alternaria. Patients have been carefully selected on the basis of a suggestive clinical history, SPTs, and RAST. For all allergenic species, at least 20 nonsensitive individuals have been tested. The sensitivity (true positive in percent of patients with disease) of Phazet was 99.4%, and its specificity (true negative in percent of patients without disease) was 99.2%. It is concluded that Phazet and SPTs with standardized extracts are equally effective in the diagnosis of immediate-type allergy and that standardized extracts have improved the diagnosis of allergy, especially for previously poorly characterized extracts, such as Alternaria.

[Limits of IgE serodiagnosis of occupational respiratory allergies]. / Intérêt et limites du diagnostic sériques des allergies respiratoires professionnelles à IgE.

In occupational respiratory diseases, it is important to establish the nature of the mechanism involved. The measurement of specific IgE is an excellent tool to prove a type I, IgE mediated, hypersensitivity. There are two distinct kinds of allergens: macromolecular allergens (storage mites, sea products...) which are technically and clinically similar to usual RAST; low molecular weight allergens (haptens such as isocyanates, formaldehyde...). In these cases, the RAST technology is different and the responsibility of specific IgE is less frequent, troubles being usually caused by irritative or toxic properties of these molecules.

Clinical evaluation of the human basophil degranulation test in grass pollen allergic patients.

The reliability of the human basophil degranulation test (HBDT) is still in doubt. We took 20 orchard grass-sensitive patients and 20 non-sensitive subjects and compared the sensitivity of HBDT with skin test and RAST. Eighteen HBDTs were positive in skin test-positive patients. There was also a good correlation with the results of RAST.

[Allergologic study of allergic asthma and therapeutic implications]. / Exploration allergologique d'un asthme allergique et conséquences thérapeutiques.

The diagnosis of allergic asthma is based on a number of clinical and paraclinical findings which should allow the appropriate therapeutic decisions to be taken. The following diagnostic procedures are available to the clinician: the clinical history which is always of prime importance, skin tests, second stage of diagnosis, total serum and specific IgE (RAST) concentrations demonstrate an IgE dependent mechanism, the human basophil degranulation test (HBDT) to assess cellular sensitivity, bronchial or nasal provocation tests which finally demonstrate the responsibility of the causative allergen. In practice, the clinical history, skin tests and the RAST are sufficient to establish the diagnosis of allergy and to take the appropriate therapeutic measures: eviction, antidegranulation therapy or specific immunotherapy.

[Human basophil degranulation test in the diagnosis and prevention of peranesthetic anaphylactoid complications]. / Le test de dégranulation des basophiles humains dans le diagnostic et la prévention des accidents anaphylactoïdes peranesthésiques.

The human basophil degranulation test (HBDT) studies the allergic response of effector cells. In this work, it was used in the diagnosis of anaphylactoid reactions during anaesthesia. Thirteen patients having had an anaphylactoid shock during general anaesthesia were investigated. An HBDT was performed with every suspected drug used during the anaesthesia. Ten patients had a positive HBDT and in five cases the drug involved was suxamethonium. In one case, the IgE-dependency of the accident was asserted by the ability of the plasma to sensitize in vitro alien basophils. These sensitized basophils degranulated in the presence of Althesin and suxamethonium. Passive sensitization was abolished when using plasma heated for 2 h at 56 degrees C. Two patients had a negative HBDT to 11 drugs tested. To assess the validity of these results, and to rule out unspecific degranulation, thirteen control patients who were to undergo general anaesthesia were investigated. HBDT was performed immediately before anaesthesia in a double-blind method with every drug to be used during the anaesthesia. The twelve patients who had a negative HBDT to every drug had an uneventful anaesthesia. One patient had a positive test to thiopentone and displayed bronchospasm and generalized urticaria during the anaesthesia. In conclusion, the HBDT appears to be a reliable test in the diagnosis of anaphylactoid reactions during anaesthesia.

[Value of basophil studies in the diagnosis of drug allergies]. / Intérêt de l'exploration des basophiles humains dans le diagnostic de l'allergie médicamenteuse.

Mastocytes and basophils are the two cell populations involved in the reactions seen during drug allergies. The testing of basophils is the only and simplest way of studying sensitization in the IgE system by a drug antigen, especially when the skin tests cannot be carried out. This study is carried out in two steps: straight after the drug-induced accident, where a basophil count will give an idea of its allergic origin; and some time after the accident, where the human basophil degranulation test (H.B.D.T.) helps to identify in over 50 p. 100 of cases the responsible drug. The basophil count and H.B.D.T. techniques are then described. The authors present their own results. In a study by H.B.D.T. of 908 patients with a drug allergy, 53.2 p. 100 had positive test; 57.6 p. 100 of 33 cases who presented an anaesthetic accident had a positive H.B.D.T.