An Attempted Suicide with Copper Sulphate injected intravenously:Pathopsysiology and Therapy about a case report

Acute copper sulphate poisoning is an unusual event, rarely following parenteral exposure, complicated by toxicological effects as haemolytic anaemia, methaemoglobinaemia , hepato-renal damage and acute rhabdomyolysis. Currently, the therapeutic management ignores unique classes of evidence and is mainly based on supportive and chelation therapies. Case details. This case report describes acute copper sulphate poisoning in a 37-year-old man who attempted suicide by self-injecting an unknown amount of copper sulphate. Within three days the patient developed severe intravascular haemolysis and rhabdomyolysis. Initial therapy relied on intensive supportive care with fluids administration, electrolyte correction and packed red blood cells transfusion. The D-penicillamine (30 mg/Kg/day per os) was prescribed as chelation therapy by the poison control centre. The N-acetilcysteine and ascorbic acid were administered to prevent further oxidative stress. Later on, two sessions of therapeutic plasma exchange were performed in order to support the drug therapy. Haemolysis and rhabdomyolysis reversed throughout the hospital stay. Discussion. In this case the antidotic and antioxidant therapy resulted effective to reverse haemolysis and rhabdomyolysis and to prevent hepatic and renal damage. Moreover, this case underlies that therapeutic plasma exchange should be considered as an additive measure to undertake since the earlier stages of the emergency intervention. Acute copper sulphate poisoning is an event complicated by toxicological effects: haemolytic anaemia, methaemoglobinaemia, hepato-renal damage, acute rhabdomyolysis. The therapeutic management ignores unique classes of evidence and is based on supportive and chelation therapies. In this case: i) the antidotic and antioxidant therapy resulted effective to reverse haemolysis and rhabdomyolysis and to prevent hepatic and renal damage, ii) therapeutic plasma exchange should be considered as an additive measure to undertake

Overview of Serological Techniques for Influenza Vaccine Evaluation: Past, Present and Future

Serological techniques commonly used to quantify influenza-specific antibodies include the Haemagglutination Inhibition (HI), Single Radial Haemolysis (SRH) and Virus Neutralization (VN) assays. HI and SRH are established and reproducible techniques, whereas VN is more demanding. Every new influenza vaccine needs to fulfil the strict criteria issued by the European Medicines Agency (EMA) in order to be licensed. These criteria currently apply exclusively to SRH and HI assays and refer to two different target groups—healthy adults and the elderly, but other vaccine recipient age groups have not been considered (i.e., children). The purpose of this timely review is to highlight the current scenario on correlates of protection concerning influenza vaccines and underline the need to revise the criteria and assays currently in use. In addition to SRH and HI assays, the technical advantages provided by other techniques such as the VN assay, pseudotype-based neutralization assay, neuraminidase and cell-mediated immunity assays need to be considered and regulated via EMA criteria, considering the many significant advantages that they could offer for the development of effective vaccines

Vitamin E requirements of adult domestic cats (Felis catus) fed diets containing high levels of fish oil : a thesis presented in partial fulfilment of the requirement for the degree of Master of Nutritional Sciences at Massey University, Palmerston North, New Zealand

The vitamin E (α-tocopherol) requirement of adult cats fed diets containing high levels of fish oil was investigated. Thirty-two (16 male, 16 female) adult domestic cats (Felis catus) were randomly allocated to four groups according to sex and fed one of four experimental diets (A, B, C, and D) for 126 days. The cats were housed in large outdoor pens in groups of 8 cats. Diets A, B, C and D contained approximately 300 g of fish oil per kg diet dry matter and were supplemented to contain 0, 5, 10, and 15 IU DL-α-tocopheryl acetate per g added fish oil per kg diet, respectively. The diets were provided ad libitum with water being available at all times. Food intake was measured daily and body weights were measured at weekly intervals. Blood samples were taken from the jugular vein of each cat at bi-weekly intervals during the study. Blood samples were analysed for plasma α-tocopherol, red blood cell H₂O₂ (4 and 2 %) haemolysis, the ferric reducing ability of plasma, plasma lipid peroxides, plasma triglycerides, alkaline phosphatase and whole blood lymphocyte proliferation. All cats remained healthy throughout the study except one female cat who was removed after 3 weeks due to poor food intake. The four diets were analysed and found to be free of peroxides. The average daily metabolisable energy intake of the cats on diet A, B, C and D at the end of study were similar and were 289, 261, 256, and 267 kJ·kg⁻¹ body weight, respectively. No clinical signs of vitamin E deficiency were observed in any of the cats. The plasma α-tocopherol concentrations of the cats in the four groups at the start of the study were not significantly different between the four groups (mean ± SEM, 3.4 ± 0.2 μg-ml⁻¹). When the cats were fed diet A (unsupplemented), the mean plasma α-tocopherol concentration remained relatively low and the RBC 4 % H₂O₂ haemolysis remained high, while the RBC 2 % H₂O₂ haemolysis decreased consistently. Plasma lipid peroxides remained relatively low throughout the study. The ferric reducing ability of plasma status was compromised in the cats on the unsupplemented diet. There was no significant (P < 0.05) difference in any of the response parameters measured amongst the cats fed diets B, C and D except for the RBC 4 % H₂O₂ haemolysis of the cats on diet B which was significantly higher than those on diet C and D at week 4 and week 8, and the LPO value of the cats on diet D which was significantly higher than those of the cats on diet B and C at week 4. The vitamin E requirement of adult cats fed a high level of fish oil, using the response parameters measured, was estimated to be between 0 and 5 IU of vitamin E per g added fish oil per kg diet. The current recommendation of the Association of American Feed Control Officials (10 IU vitamin E/g fish oil/kg diet) appears to be well in excess. The results from the present study also showed that there was no beneficial effect of dietary vitamin E on whole blood cell proliferation when vitamin E levels were 150 % of the recommendations of the Association of American Feed Control Officials. The vitamin E requirement of adult cats to optimise immune response warrants further investigation

Synthesis and cellular penetration properties of new phosphonium based cationic amphiphilic peptides

A new category of phosphonium based cationic amphiphilic peptides has been developed and evaluated as potential antimicrobial peptides and cell penetrating peptides. The required building blocks were conveniently accessible from cysteine and could be applied in a solid phase peptide synthesis protocol for incorporation into peptide sequences. Evaluation of the antimicrobial properties and cellular toxicity of these phosphonium based peptides showed that these “soft” cationic side-chain containing peptides have poor antimicrobial properties and most of them were virtually non toxic (on HEK cells tested at 256 and 512 μM) and non-haemolytic (on horse erythrocytes tested at 512 μM), hinting at an interesting potential application as cell penetrating peptides. This possibility was evaluated using fluorescent peptide derivatives and showed that these phosphonium based peptide derivatives were capable of entering HEK cells and depending on the sequence confined to specific cellular areas

Novel Molecules for Intra-Oral Delivery of Antimicrobials to Prevent and Treat Oral Infectious Diseases

New molecules were designed for efficient intra-oral delivery of antimicrobials to prevent and treat oral infection. The salivary statherin fragment, which has high affinity for the tooth enamel, was used as a carrier peptide. This was linked through the side chain of the N-terminal residue to the C-terminus of a defensin-like 12-residue peptide to generate two bifunctional hybrid molecules, one with an ester linkage and the other with an anhydride bond between the carrier and the antimicrobial components. They were examined for their affinity to a HAP (hydroxyapatite) surface. The extent of the antimicrobial release in human whole saliva was determined using 13C-NMR spectroscopy. The candidacidal activity of the molecules was determined as a function of the antimicrobial release from the carrier peptide in human saliva. The hybrid-adsorbed HAP surface was examined against Candida albicans and Aggregatibacter actinomycetemcomitans using the fluorescence technique. The bifunctional molecules were tested on human erythrocytes, GECs (gingival epithelial cells) and GFCs (gingival fibroblast cells) for cytotoxicity. They were found to possess high affinity for the HAP mineral. In human whole saliva, a sustained antimicrobial release over a period of more than 40–60 h, and candidacidal activity consistent with the extent of hybrid dissociation were observed. Moreover, the bifunctional peptide-bound HAP surface was found to exhibit antimicrobial activity when suspended in clarified human saliva. The hybrid peptides did not show any toxic influence on human erythrocytes, GECs and GFCs. These novel hybrids could be safely used to deliver therapeutic agents intra-orally for the treatment and prevention of oral infectious diseases

ANTIOXIDANT AND TOXICITY ACTIVITY IN VITRO OF TWELVE SAFROLE DERIVATIVES

Indexación: Web of Science; Scielo.The aim of this study was to determine the influence of substituents in aromatic ring and the side chain of safrole on the antioxidant capacity and toxicity of twelve synthetic derivatives of safrole (S1-S12). Each compound was analyzed by two antioxidant methods: DPPH and bleaching of β-carotene (DBC). Among the derivates of safrol assayed, S5, S6, S9, S10 and S11 showed the strongest antioxidant capacity: DPPH method, first order specific rate constant (0.0152, 0.0211, 0.0432, 0.0317 and 0.0072) and DBC (22.41 ± 0.13%, 10.71 ± 0.05 %, 9.12 ± 0.89 %, 30.97 ± 0.92 % and 19.08 ± 0.31 %), respectively. The toxicity of the active compounds was evaluated by means of two techniques, Artemia salina, LD50 (4466 ± 1057 ppm, 630 ± 108 ppm, 1513 ± 797 ppm, 1585 ± 317 ppm, 1259 ± 242 ppm) and red cells, Haemolysis (1.58 ± 0.98%, 4.02 ± 2.03%, 8.42 ± 1.38%, 2.59 ± 2.31%, 2.92 ± 0.52%), to provide preliminary information that can be used as a basis for further studies to contribute to the search for new antioxidants.http://ref.scielo.org/9sqp8

Age-Related Reference Intervals of the Main Biochemical and Hematological Parameters in C57BL/6J, 129SV/EV and C3H/HeJ Mouse Strains

BACKGROUND: Although the mouse is the animal model most widely used to study the pathogenesis and treatment of human diseases, reference values for biochemical parameters are scanty or lacking for the most frequently used strains. We therefore evaluated these parameters in the C57BL/6J, 129SV/EV and C3H/HeJ mice. METHODOLOGY/PRINCIPAL FINDINGS: We measured by dry chemistry 26 analytes relative to electrolyte balance, lipoprotein metabolism, and muscle/heart, liver, kidney and pancreas functions, and by automated blood counter 5 hematological parameters in 30 animals (15 male and 15 female) of each mouse strain at three age ranges: 1-2 months, 3-8 months and 9-12 months. Whole blood was collected from the retro-orbital sinus. We used quality control procedures to investigate analytical imprecision and inaccuracy. Reference values were calculated by non parametric methods (median and 2.5(th) and 97.5(th) percentiles). The Mann-Whitney and Kruskal-Wallis tests were used for between-group comparisons. Median levels of GLU, LDH, Chol and BUN were higher, and LPS, AST, ALP and CHE were lower in males than in females (p range: 0.05-0.001). Inter-strain differences were observed for: (1) GLU, t-Bil, K+, Ca++, PO(4)- (p<0.05) and for TAG, Chol, AST, Fe++ (p<0.001) in 4-8 month-old animals; (2) for CK, Crea, Mg++, Na++, K+, Cl- (p<0.05) and BUN (p<0.001) in 2- and in 10-12 month-old mice; and (3) for WBC, RBC, HGB, HCT and PLT (p<0.05) during the 1 year life span. CONCLUSION/SIGNIFICANCE: Our results indicate that metabolic variations in C57BL/6J, 129SV/EV and C3H/HeJ mice after therapeutic intervention should be evaluated against gender- and age-dependent reference intervals

Temperature-dependent release of ATP from human erythrocytes: Mechanism for the control of local tissue perfusion

Copyright @ 2012 The AuthorsThis article has been made available through the Brunel Open Access Publishing Fund.Human limb muscle and skin blood flow increases significantly with elevations in temperature, possibly through physiological processes that involve temperature-sensitive regulatory mechanisms. Here we tested the hypothesis that the release of the vasodilator ATP from human erythrocytes is sensitive to physiological increases in temperature both in vitro and in vivo, and examined potential channel/transporters involved. To investigate the source of ATP release, whole blood, red blood cells (RBCs), plasma and serum were heated in vitro to 33, 36, 39 and 42°C. In vitro heating augmented plasma or ‘bathing solution’ ATP in whole blood and RBC samples, but not in either isolated plasma or serum samples. Heat-induced ATP release was blocked by niflumic acid and glibenclamide, but was not affected by inhibitors of nucleoside transport or anion exchange. Heating blood to 42°C enhanced (P < 0.05) membrane protein abundance of cystic fibrosis transmembrane conductance regulator (CFTR) in RBCs. In a parallel in vivo study in humans exposed to whole-body heating at rest and during exercise, increases in muscle temperature from 35 to 40°C correlated strongly with elevations in arterial plasma ATP (r2 = 0.91; P = 0.0001), but not with femoral venous plasma ATP (r2 = 0.61; P = 0.14). In vitro, however, the increase in ATP release from RBCs was similar in arterial and venous samples heated to 39°C. Our findings demonstrate that erythrocyte ATP release is sensitive to physiological increases in temperature, possibly via activation of CFTR-like channels, and suggest that temperature-dependent release of ATP from erythrocytes might be an important mechanism regulating human limb muscle and skin perfusion in conditions that alter blood and tissue temperature.This article is made available through the Brunel Open Access Publishing Fund