REDUCED CARDIOTOXICITY AND INCREASED CYTOTOXICITY IN A NOVEL ANTHRACYCLINE ANALOG, 4'-AMINO-3'-HYDROXY-DOXORUBICIN

The acute and chronic cardiotoxicity and cytotoxicity of the novel doxorubicin (DXR) derivative 4'-amino-3'-hydroxy-DXR were compared with those of 4'-deoxy-DXR and DXR. In the acute cardiotoxicity study, the ECG and hemodynamic changes recorded in anesthetized rats that had been treated i.v. with 10 mg/kg 4'-amino-3'-hydroxy-DXR or 8.6 mg/kg 4'-deoxy-DXR were significantly less severe than those caused by 13 mg/kg DXR. In the chronic cardiotoxicity study, rats received 3 weekly i.v. injections of 3 mg/kg DXR, 3 mg/kg 4'-amino-3'-hydroxy-DXR, or 2 mg/kg 4'-deoxy-DXR during the first 14 days of the study and were observed for an additional 35-day period. DXR induced severe cardiomyopathy that was characterized by ECG changes in vivo (S-alpha-T-segment widening and T-wave flattening) and by impairment of the contractile responses (F(max), +/- dF/dt(max)) to adrenaline of hearts isolated from treated animals. 4'-Deoxy-DXR caused a progressive enlargement of the S-alpha-T segment in vivo and a significant impairment of the - dF/dt(max) value in vitro, which were less severe than those produced by DXR. The least cardiotoxic drug was 4'-amino-3'-hydroxy-DXR, which induced minor ECG changes without causing significant alterations in the contractile responses of isolated hearts to adrenaline. On the basis of the drug concentration required to inhibit 50% of the colony formation (IC50) of cell lines in vitro, 4'-amino-3'-hydroxy-DXR was less active than 4'-deoxy-DXR but at least twice as active as DXR against human cancer and murine transformed cell lines. These data indicate that 4'-amino-3'-hydroxy-DXR is significantly less cardiotoxic and more cytotoxic than DXR

Antimicrobial activity and composition of five rosmarinus (Now salvia spp. and varieties) essential oils

Salvia rosmarinus Spenn. and Salvia jordanii J.B.Walker are aromatic evergreen shrubs belonging to the Lamiaceae family. Their aerial parts have been used since ancient times as natural preservatives. The present study reported the investigation of the chemical profile and the extraction yield of the essential oils (EOs) obtained from the dried aerial parts of four cultivars of Salvia rosmarinus (‘Boule’; ‘Vicomte de Noailles’; ‘Gorizia’; ‘Joyce de Baggio’) and the species S. jordanii, together with their antibacterial and antifungal activities. The phytochemical investigation evidenced a predominance of oxygenated monoterpenes in all the samples (57.5–77.1%), except in ‘Boule’, in which the hydrocarbon form prevailed (50.2%). Principal Component Analysis (PCA) of the matrix taxa × compounds showed that nine compounds have a significant discriminating function between the samples. ‘Vicomte de Noailles’ was characterized by high amounts of camphor and 14-hydroxy-9-epi-(E)-caryophyllene, while ‘Gorizia’ and Jord differed in their predominance of camphene, borneol, bornyl acetate, and α-humulene. Lastly, ‘Boule’ and ‘Joyce de Baggio’ segregated separately and were characterized by high amounts of α-pinene, myrcene, and verbenone. The selected EOs presented a moderate antibacterial activity on the tested bacterial strains and resulted not active on the tested yeast species

Sexual Dimorphism in Hematocrit Response Following Red Blood Cell Transfusion of Critically Ill Surgical Patients

The change in hematocrit (ΔHct) following packed red blood cell (pRBCs) transfusion is a clinically relevant measurement of transfusion efficacy that is influenced by post-transfusion hemolysis. Sexual dimorphism has been observed in critical illness and may be related to gender-specific differences in immune response. We investigated the relationship between both donor and recipient gender and ΔHct in an analysis of all pRBCs transfusions in our surgical intensive care unit (2006–2009). The relationship between both donor and recipient gender and ΔHct (% points) was assessed using both univariate and multivariable analysis. A total of 575 units of pRBCs were given to 342 patients; 289 (49.9%) donors were male. By univariate analysis, ΔHct was significantly greater for female as compared to male recipients (3.81% versus 2.82%, resp., P < 0.01). No association was observed between donor gender and ΔHct, which was 3.02% following receipt of female blood versus 3.23% following receipt of male blood (P = 0.21). By multivariable analysis, recipient gender remained associated significantly with ΔHct (P < 0.01). In conclusion, recipient gender is independently associated with ΔHct following pRBCs transfusion. This association does not appear related to either demographic or anthropomorphic factors, raising the possibility of gender-related differences in recipient immune response to transfusion

Every Dog Has Its Data:Evaluation of a Technology-Aided Canine Rabies Vaccination Campaign to Implement a Microplanning Approach

Background: Robust dog vaccination coverage is the primary way to eliminate canine rabies. Haiti conducts annual canine mass vaccination campaigns, but still has the most human deaths in the Latin American and Caribbean region. We conducted an evaluation of dog vaccination methods in Haiti to determine if more intensive, data-driven vaccination methods, using smartphones for data reporting and geo-communication, could increase vaccination coverage to a level capable of disrupting rabies virus transmission.Methods: Two cities were designated into “Traditional” and “Technology-aided” vaccination areas. Traditional areas utilized historical methods of vaccination staff management, whereas Technology-aided areas used smartphone-supported spatial coordination and management of vaccination teams. Smartphones enabled real time two-way geo-communication between campaign managers and vaccinators. Campaign managers provided geographic instruction to vaccinators by assigning mapped daily vaccination boundaries displayed on phone handsets, whilst vaccinators uploaded spatial data of dogs vaccinated for review by the campaign manager to inform assignment of subsequent vaccination zones. The methods were evaluated for vaccination effort, coverage, and cost.Results: A total of 11,420 dogs were vaccinated during the 14-day campaign. The technology-aided approach achieved 80% estimated vaccination coverage as compared to 44% in traditional areas. Daily vaccination rate was higher in Traditional areas (41.7 vaccinations per team-day) compared to in technology-aided areas (26.8) but resulted in significantly lower vaccination coverages. The cost per dog vaccinated increased exponentially with the associated vaccination coverage, with a cost of $1.86 to achieve 25$2.51 for 50% coverage, and $3.19 for 70% coverage.Conclusions: Traditional vaccination methods failed to achieve sufficiently high vaccination coverages needed to interrupt sustained rabies virus transmission, whilst the technology-aided approach increased coverage above this critical threshold. Over successive campaigns, this difference is likely to represent the success or failure of the intervention in eliminating the rabies virus. Technology-aided vaccination should be considered in resource limited settings where rabies has not been controlled by Traditional vaccination methods. The use of technology to direct health care workers based on near-real-time spatial data from the field has myriad potential applications in other vaccination and public health initiatives

Sicurezza e Resilienza delle Infrastrutture

Negli ultimi anni si sono manifestati eventi calamitosi che hanno causato collassi, completi o parziali nelle reti infrastrutturali in numerose aree nel mondo. A fronteggiare tali calamità intervengono la pubblica amministrazione e/o i gestori della rete che, collaborando a volte anche con associazioni e organizzazioni private e di volontariato, operano per ripristinare le prestazioni originarie del sistema. In particolar modo le infrastrutture critiche, cioè quei sistemi legati ai servizi di comunicazione, distribuzione dell’energia, sanità, tecnologia dell’informazione, sistemi finanziari/bancari, trasporti e sistemi idrici che forniscono i servizi essenziali per l’economia, la sicurezza e la stabilità di una Nazione, devono essere salvaguardate dai disastri. Il sistema di trasporto è essenziale per il benessere delle comunità, specialmente in condizioni avverse in quanto fornisce la possibilità di evacuazione, delle operazioni di salvataggio e facilita il ripristino dei servizi per la comunità, data la sua vasta interconnessione con tutte le altre infrastrutture critiche. Le caratteristiche e la capacità di un determinato territorio atte a fronteggiare gli eventi calamitosi dipendono da numerosi aspetti che possono essere riassunti nei concetti di sostenibilità, vulnerabilità e resilienza. Gli approcci definiti come disaster risk, climate change e quello basato sulla resilienza sono gli strumenti di valutazione maggiormente utilizzati e innovativi. La recente introduzione di questi concetti e degli approcci citati comporta un ventaglio di definizioni non univoche nella letteratura tecnica. Il presente lavoro ha lo scopo di: 1) Fornire una revisione critica e comparata della letteratura tecnica sull’argomento; 2) Analizzare gli attuali approcci che mirano ad incrementare la resilienza di una infrastruttura legata al trasporto, in particolar modo nei confronti di eventi rari (es. alluvioni, frane, ecc.); 3) Individuare i fattori e le azioni che influiscono sul ripristino delle performance del sistema; 4) Elaborare un metodo di valutazione della resilienza di tipo gerarchico

Clinical Manifestations of an Outbreak of Monkeypox Virus in Captive Chimpanzees in Cameroon, 2016

Monkeypox virus (MPXV) is a re-emerging virus of global concern. An outbreak of Clade I MPXV affected 20 captive chimpanzees in Cameroon in 2016. We describe the epidemiology, virology, phylogenetics, and clinical progression of this outbreak. Clinical signs included exanthema, facial swelling, peri-laryngeal swelling, and eschar. Mpox can be lethal in captive chimpanzees with death likely resulting from respiratory complications. We advise avoiding anesthesia in animals with respiratory signs to reduce the likelihood of death. This outbreak presented a risk to animal care staff. There is a need for increased awareness and a One Health approach to preparation for outbreaks in wildlife rescue centers in primate range states where MPXV occurs. Control measures should include quarantining affected animals, limiting human contacts, surveillance of humans and animals, use of personal protective equipment, and regular decontamination of enclosures.</p

Detrimental effect of apoptosis of lymphocytes at an early time point of experimental abdominal sepsis

<p>Abstract</p> <p>Background</p> <p>Apoptosis of lymphocytes is considered a late sequelum in the sepsis cascade. The role of apoptosis of lymphocytes as a driver of final outcome was investigated.</p> <p>Methods</p> <p>Abdominal sepsis was induced after cecal ligation and puncture (CLP) in 31 rabbits. Blood was sampled at serial time intervals and peripheral blood mononuclear cells (PBMCs) were isolated. Apoptosis of lymphocytes and monocytes was measured through flow cytometric analysis. PBMCs were stimulated with LPS and Pam3Cys for the release of tumor necrosis factor-alpha (TNFα). Tissue bacterial growth was quantitatively measured. In a second set of experiments, CLP was performed in another 40 rabbits; 20 received single intravenous infusions of ciprofloxacin and of metronidazole 4 hours after surgery.</p> <p>Results</p> <p>Animals were divided into two groups based on the percentage of lymphocyte apoptosis at 4 hours after surgery; less than or equal to 32% and more than 32%. Survival of the former was shorter than the latter (p: 0.017). Tissue growth was similar between groups. Apoptosis of lymphocytes and of monocytes was lower in the former group over follow-up. Release of ΤNFα did not differ. The above findings on survival were repeated in the second set of experiments. Administration of antimicrobials prolonged survival of the former group (p: 0.039) but not of the latter group (pNS).</p> <p>Conclusions</p> <p>Lymphocyte apoptosis at an early time point of experimental peritonitis is a major driver for death. A lower percentage of apoptosis leads earlier to death. Antimicrobials were beneficial even at that disease state.</p