Glutathionyl-hemoglobin levels in carotid endarterectomy: a pilot study on 12 cases clinically uneventful.

Aim: Carotid endarterectomy is a widely accepted procedure for stroke prevention, and carotid clamping is a necessary surgical step. Glutathionylated haemoglobin (HbSSG) has been recently employed as a biomarker of oxidative stress, its level being increased under several conditions, including hypoxia. This study aims to evaluating whether HbSSG level in peripheral and/or jugular blood is affected during carotid surgery under normal routine operative conditions. Methods: This study enrolled 13 consecutive patients undergoing elective carotid endarterectomy under general anesthesia. At different times during surgery, blood was taken simultaneously from both a peripheral vein and the jugular vein ipsilateral to the clamped carotid. HbSSG was measured in RBC hemolysates by MALDI-ToF mass spectrometry in each sample. Results: Three patients showed a complex pattern of rise and fall of HbSSG levels in different time periods before, during and after surgery. They also showed statistically significant differences between peripheral and jugular blood, with mean HbSSG levels in jugular blood higher by approx. 30% than those of peripheral blood at the end of the period of carotid clamping. In all three patients HbSSG levels fell to pre-clamping values within 2 min from removal of carotid artery clamp. Conclusion: Although effective routine drug management allowed brain safety during carotid clamping time, a number of patients showed a fast modification over time of the HbSSG levels in jugular blood, suggesting that "resident" cerebral biochemical protection mechanisms could play some role to compensate clinically silent brain oxidative stress.

Evaluation of a rapid device for serological diagnosis of Leishmania infantum infection in dogs as an alternative to immunofluorescence assay and Western blotting.

In this study, we compared a rapid immunochromatographic test (Speed Leish K; BVT Groupe Virbac, La Seyne sur Mer, France) with an indirect immunofluorescence assay (IFAT) and Western blotting (WB) for the detection of Leishmania infantum antibodies in dogs. A total of 250 serum samples were collected from 125 L. infantum-positive and 125 L. infantum-negative dogs. Among the positive samples, 81 were strongly positive at low IFAT dilutions, while 44 were low-reactivity sera (IFAT titers, 1:40 to 1:80). The sensitivity and specificity of the Speed Leish K were 96.3% and 100%, respectively, compared with those of the IFAT. When IFAT low-reactivity sera (titers, 1:40 or 1:80) were tested with the Speed Leish K, using WB results as a reference, the sensitivities were 93.75% for sera with a 1:80 titer and 73.33% for sera with a 1:40 titer, and the specificity was 100%. The Speed Leish K is easy to use and performs well, so it can be considered a quick and reliable tool for the diagnosis of L. infantum infection in dogs.

Therapeutic and prophylactic efficacy of milbemycin oxime (Interceptor) against Thelazia callipaeda in naturally exposed dogs.

Two trials were conducted to evaluate the therapeutic and prophylactic activity of milbemycin oxime (Interceptor, Novartis Animal Health) against the eye-worm Thelazia callipaeda (Spirurida, Thelaziidae) infection. In Trial 1, the therapeutic efficacy of milbemycin oxime was evaluated in 55 naturally infected dogs treated with min. 0.5mg/kg milbemycin oxime. The dogs were clinically examined for the presence of eyeworms before and again 7 days after treatment. Dogs still positive were given a second treatment and re-checked again a week later. Forty-eight of the 55 dogs tested negative 1 week after treatment (87.3% reduction of infection rate). Following the second treatment 6 of these 7 dogs tested negative 1 week later resulting, after two treatments, in a reduction of infection rate of 98.2%. In Trial 2, the prophylactic efficacy of milbemycin oxime was evaluated in 60 uninfected dogs. Thirty dogs were treated with milbemycin oxime monthly from June to November with the recommended dose rate for the prevention of heartworm disease (> or =0.5mg/kg), 30 dogs served as untreated controls. At the end of the trail 1 dog in the treated group and 10 dogs in the control group became infected during the trial. The incidence of infection differed significantly between treated and control dogs (p=0.0056). The efficacy of the prophylactic use of a monthly treatment with milbemycin oxime showed 90% efficacy in reducing T. callipaeda infection rate.

Treatment of dog thelaziosis caused by Thelazia callipaeda (Spirurida, Thelaziidae) using a topical formulation of imidacloprid 10% and moxidectin 2.5%.

Canine thelaziosis caused by Thelazia callipaeda infects dogs, cats, foxes, rabbits, and humans resulting in conjunctivitis, pain and excessive lacrimation. T. callipaeda live in the eyes under the nictitating membrane and females release first stage larvae which are ingested by flies which act as intermediate hosts. Control of canine thelaziosis is currently based on the removal of nematodes directly from the eyes of affected dogs or on the local instillation of antiparasitic drugs. With the aim of evaluating the efficacy against T. callipaeda of an association of imidacloprid 10% and moxidectin 2.5% by spot-on formulation administered via dermal application, three groups of naturally infected animals were selected: i.e. group A (21 dogs) received a single dose of imidacloprid 10% and moxidectin 2.5% by spot-on; group B (21 dogs) received a single dose of imidacloprid 10% by spot-on and group C (20 dogs) were left untreated. The efficacy of treatments was established by eye inspection and parasite viability and vitality after 1, 5 and 9 days after animal treatments (groups A and B) and after 9 days only in untreated animals (group C). Imidacloprid 10% and moxidectin 2.5% in spot-on formulation showed to be effective with regards the control of dog thelaziosis within 5 (90.47%) to 9 (95.23%) days after treatment. Only one dog from group A presented nematodes after treatment. The presence of parasites in the eyes of dogs from groups B (imidacloprid 10%) and C confirm that the anthelmintic efficacy against T. callipaeda in animal from group A (imidacloprid 10% and moxidectin 2.5%) was most likely attributable to moxidectin 2.5%. The spot-on formulation containing imidacloprid 10% and moxidectin 2.5% is very easy to apply and helps overcome problems linked to the mechanical removal of parasites or to the restraining of the animals for the local instillation of drugs in the eyes.

Efficacy of imidacloprid on dogs and cats with natural infestations of fleas, with special emphasis on flea hypersensitivity.

In this study the efficacy of a 10% weight per volume solution of imidacloprid--registered as a flea control agent with the trademark Advantage topical solution--was assessed in Italy under field conditions in a total of 3272 dogs and cats. During the 4-week trial the number of fleas on each animal was assessed and lesions of flea allergy dermatitis (FAD; i.e., miliary or maculopapular dermatitis, hyperpigmentation, and crusty thickenings of the skin), alopecia, and pruritus were evaluated. Imidacloprid had a notable adulticidal effect and residual activity that controlled fleas and prevented reinfestation of treated animals for at least 4 weeks. In addition, a significant decrease of the clinical signs was documented regardless of each animal's breed, sex, body size, haircoat length, and living conditions. Some of the dogs were washed or shampooed after treatment without showing statistical differences in efficacy. This study demonstrates that a single treatment with imidacloprid is able to effectively control flea infestations in dogs and cats for at least 28 days and significantly contributes to the improvement or disappearance of clinical signs of FAD.

[Vascular pathology. A study of some blood parameters indicative of leukocyte activation and platelet dysfunction]. / Patologia vascolare. Studio di alcuni parametri ematici indicativi di attivazione leucocitaria e disfunzione piastrinica.

BACKGROUND: In vascular pathology the endothelial lesions easily reflect on blood cells, inducing a reactive state. In the present study the eventual presence of activation signals in leukocytes and platelets was tested. METHODS: Fifty-eight subjects with major vascular pathology and 14 with lower limbs venous insufficiency were studied, together with a control group of 25 normal subjects. Elastase PMN, superoxide ion, leukocytes and subpopulation count, platelet factor 3, clot retraction, heparin in neutralizing activity (HNA plasmatic and intraplatelet), platelet count and volume were tested. RESULTS: As regards leukocytes, it was observed a significative increase of elastase PMN and monocytes number for both the studied pathologies, of superoxide ion and leukocyte number only for major vascular pathology; for platelets, an inhibition of functionality, revealed by clot retraction test for arterious and venous pathologies and by HNA test only for the venous one. CONCLUSIONS: As regards the leukocyte activation, elastase PMN is particularly responsive to the endothelial lesion both in arterious and in venous districts, while superoxide ion appears to increase in presence of a marked alteration. The level of monocytes is indicative of an inflammatory condition and of leukocytes of an atherosclerotic inflammatory process. As for platelets, the test clot retraction is specifically sensible to the endothelial abnormality in both the arterious and venous pathologies with addition of an abnormal HNA test only in venous insufficiency. This platelet dysfunction is probably due to endothelial release of vasoactive and heparin amplifying substances.

[Heparan sulfate in the therapy of postphlebitic syndrome. Evaluation of the efficacy and tolerability as compared to mesoglycan]. / Eparansolfato nella terapia a medio termine della sindrome postflebitica. Valutazione dell'efficacia e della tollerabilità nei confronti del mesoglicano.

BACKGROUND: Antithrombotics and profibrinolytics are indicated in several clinical thrombophilic conditions such as postphlebitic syndrome. Heparansulphate, a glycosaminoglycan, shows an antithrombotic activity with low anticoagulant effect. The aim of the study was to evaluate the efficacy and the safety of heparansulphate (100 mg b.i.d.) versus mesoglycan (50 mg b.i.d.), both administered for three months in patients with postphlebitic syndrome. METHODS: The trial was performed in an open-label, controlled, with parallel and randomized groups, design. Thirty patients, with chronic venous insufficiency and a history of venous thrombosis were enrolled. Coagulative and fibrinolytic parameters (PT, aPTT, euglobulin lysis time, fibrinogen, D-dimer, t-PA, PAI-1) and signs and symptoms (cramps, paresthesia, itch, edema, local pain, skin trophism) were assessed at enrollment, 15 days later after the pharmacological washout period and after 1, 2, 3 months of treatment. Safety was evaluated by monitoring any adverse event during the study and performing clinical laboratory tests at the beginning and at the end of treatment. RESULTS: The two drugs showed a superimposable efficacy and very good tolerability. Coagulative and fibrinolytic parameters were positively affected by both treatments and the clinical benefit was particularly evident in the heparansulphate group with a significant decrease "between times" of local pain, edema, paresthesia and itching. CONCLUSIONS: These data support the use of heparansulphate, and in general of glycosaminoglycans, in the postflebitic syndrome.

Degradation behaviour of ionic stepwise polyaddition polymers of medical interest.

The aim of this presentation is to review some of our recent work mostly on poly(amidoamine)s (PAAs) and some other families of polymers structurally related to PAAs of medical interest. PAAs are obtained by stepwise polyaddition of primary monoamines, or bis secondary amines, to bisacrylamides. There are several other ter-amino polymers structurally related to PAAs, such poly(amido phosphine)s (PAPs), poly(ester-amine)s (PEAs), poly(ketone-amine)s (PKAs), poly(amidothioeteramine)s (PATAs) poly(esterthioether amine)s (PTEAs), and poly(sulphone thioetheramine)s (PSTAs). Most of the PAAs exhibit heparin complexing ability. PAAs are also being considered as soluble carriers for delivering anti-cancer drugs. Some of these polymers have been studied as antimicrobial agents. PAAs with different structures degrade at different rates under physiological conditions. The degradation rate is also strongly influenced by pH. The quaternarized PATAs and PTEAs are reasonably stable over a period of some days, but ultimately degrade to oligomeric products, while the quaternized PAAs do rapidly degrade.

Recent results on functional polymers and macromonomers of interest as biomaterials or for biomaterial modification.

Different families of functionalized polymers with potential as biomaterials, or for biomaterial modification, have been investigated. In particular, degradation studies have been performed on poly(amidoamines), a family of polymers obtained by polyaddition of amines to bisacrylamides, and endowed with heparin-complexing ability. Some new poly(amidoamines) with more resistance towards hydrolytic degradation than traditional ones have been discovered. Other ter-amino polymers deriving from the polyaddition of ter-amino functionalized bis-thiols to bis-acrylic esters, or other activated unsaturated compounds, have been studied. Their quaternarization products have been proven, in a parallel work, to act as powerful antimicrobial agents. By performing in situ the polyaddition reaction, semi-interpenetrated networks based on silicone rubber and the same polymers have been prepared. Finally, end-functionalized amphiphilic oligomers have been prepared by radical polymerization techniques, and their use for enzyme modification considered.

A comparison between the hemolytic and antibacterial activities of new quaternary ammonium polymers.

New quaternary ammonium polymers, which in a previous work had shown relevant antibacterial properties, have been investigated as regards to their hemolytic activity (HA) in comparison with a low molecular weight commercial antibacterial agent, Steramine G (SG). All polymers exhibit negligible, or at most modest, HA at dosages and contact times at which SG is strongly hemolytic.

[Hemostatic factors of endothelial origin in major vascular pathology]. / Fattori emostatici di origine endoteliale in patologia vascolare maggiore.

There is an altered hemostatic balance in vascular-based diseases. The aim of this study was to compare a group (no. = 38) of vascular patients (aortic aneurysm, carotid obstructions arteriopathies of lower limbs) and a control group (no. = 40) and assess variations in the following endothelial factors: tPA, PAI1, vWf, fibronectin and dimer D, in differentiated degrees according to the type of pathology. These were the indicative signs of endothelial mobilization resulting in the renewed continuity of the stratum with the formation of a hemostatic plug. vWf was found to be particularly significant as a marker of an ongoing atheromasic process and its extension to various vascular districts.

[Major interventions in vascular surgery with and without autotransfusion. Comparison of coagulation and hemodynamic parameters]. / Interventi di chirurgia vascolare maggiore con e senza autotrasfusione. Confronto di parametri coagulativi ed emodinamici.

Twenty out of 32 patients undergoing major vascular surgery received autologous blood transfusion and hemostatic and hematological parameters were evaluated in both transfused and non-transfused groups. Blood and urine samples were also analysed. No acceleration of the hemostatic process was observed during either surgery or the postoperative period; free hemoglobin present in reinfusion sacks (?), even in high doses, was immediately restored to normal values in the patient's circulation. A slight effect was observed at the renal level alone. These findings confirm the good qualitative level of the procedures used to reinfuse blood lost during surgery.

Polymer-mediated electrostatic interactions between charged lipid assemblies and electrolyte solutions: a tentative model of the polyethylene glycol-induced cell fusion.

We developed a theoretical model to investigate the interaction between charged lipid aggregates and a water solution containing ions and uncharged polymers. The local concentration of ions and polymer chains around the lipid aggregate have been treated as variational parameters which can be found by minimizing the total energy of the system. We divided the energy into the following main contributions: (a) Solvation energy of the ions. This depends on the local polymer concentration through the variation of the solvent dielectric properties. (b) Ions-lipid aggregate interactions. These depend on the local concentrations both of the ion cloud and polymer chains. (c) Conformational energy of the polymer. This term is related to the inhomogeneous spatial density of the polymer segments. Any direct interaction between the charged lipid surface and the polymer coils has been intentionally neglected. The minimization procedure leads to a non-linear Poisson-Boltzmann equation coupled with a non-linear algebraic equation describing the polymer distribution. The solution of the above system allows one to calculate the ions and polymer spatial distribution around the lipid aggregate. The knowledge of such parameters is useful to predict the effect of non-ionic polymers on the structure and properties of lipid assemblies such as the mean area per lipid molecule, the aggregation number, the critical micellar concentration and the formation of immiscibility gaps in mixed lipid systems. A possible involvement of these parameters into the fusion process between lipid vesicles is discussed.

Effects of carnitine and acetylcarnitine isomers on mitochondrial respiration.

Mitochondrial respiration was studied in the presence of carnitine or acetyl-carnitine isomers. The results demonstrate that 15 mM L-acetylcarnitine stimulates oxygen consumption by approximately 25%. D-acetylcarnitine (15 mM) had a slight inhibitory effect whereas racemic DL-acetylcarnitine (15 mM) markedly inhibited mitochondrial respiration. Similarly racemic DL-carnitine showed approximately 60% inhibition of mitochondrial respiration. L-carnitine or D-carnitine showed no significant effect on oxygen consumption. Further studies will be required to establish whether the carnitine or acetylcarnitine isomers competitively inhibit the acylcarnitine translocase systems of the mitochondrial membrane.

[Antibacterial chemotherapy in resuscitation. Our clinical experience]. / Chemioterapia antibatterica in rianimazione. Nostra esperienza clinica.

Experience with antibiotic management in a resuscitation centre between 1974 and 1978 is described. An account is given of the incidence of bacteria in excreate, urine, blood, etc. cultures, and of the sensitivity of germs most commonly encountered in such centres to single antibiotics. It is shown that Gram-negative bacteria, particularly Pseudomonas aeruginosa, predominate, and the way in which their sensitivity to antibiotics varies in the course of time is examined. Preparation of an "overall antibiogram" based on assessment of the data made it clear that aminoglycosides and cephalosporins are the drugs of choice for Gram-negative forms, and cephalosporins for Gram-positive bacteria. A critical survey of the results leads to the suggestion that four changes should be made in the approach to antibiotic therapy: 1) elimination of the practice of "preventive" therapy in the form of "initial cover"; 2) withdrawals on admission for bacteriological determinations; 3) abstention or administration of a low-toxicity antibiotic (one of the penicillins) in the case of "minor" infection; 4) employment of potent bactericides of the aminoglycoside group or the polymixines only in cases of superinfection with evidence of septicaemia supported by an antibiogram. It is felt that the essential premiss to sound antibiotic management is the removal of other routes where by infection can enter. Drastic supplementary measures must be taken with regard to the architecture of the premises and the sterilisation of material. Staff training is also essential to prevent the spread of infection from hyperseptic patients.