Showing papers on "Animal mortality published in 2013"
TL;DR: Analysis of bacterial communities associated with the purple gorgonian Paramuricea clavata, one of the most affected species, collected at different geographic locations and depth suggests that anthropogenic influence may play a significant role in determining the coral health status by affecting the composition of the associated microbial community.
Abstract: Mass mortality events of benthic invertebrates in the Mediterranean Sea are becoming an increasing concern with catastrophic effects on the coastal marine environment. Sea surface temperature anomalies leading to physiological stress, starvation and microbial infections were identified as major factors triggering animal mortality. However the highest occurrence of mortality episodes in particular geographic areas and occasionally in low temperature deep environments suggest that other factors play a role as well. We conducted a comparative analysis of bacterial communities associated with the purple gorgonian Paramuricea clavata, one of the most affected species, collected at different geographic locations and depth, showing contrasting levels of anthropogenic disturbance and health status. Using massive parallel 16SrDNA gene pyrosequencing we showed that the bacterial community associated with healthy P. clavata in pristine locations was dominated by a single genus Endozoicomonas within the order Oceanospirillales which represented ∼90% of the overall bacterial community. P. clavata samples collected in human impacted areas and during disease events had higher bacterial diversity and abundance of disease-related bacteria, such as vibrios, than samples collected in pristine locations whilst showed a reduced dominance of Endozoicomonas spp. In contrast, bacterial symbionts exhibited remarkable stability in P. clavata collected both at euphotic and mesophotic depths in pristine locations suggesting that fluctuations in environmental parameters such as temperature have limited effect in structuring the bacterial holobiont. Interestingly the coral pathogen Vibrio coralliilyticus was not found on diseased corals collected during a deep mortality episode suggesting that neither temperature anomalies nor recognized microbial pathogens are solely sufficient to explain for the events. Overall our data suggest that anthropogenic influence may play a significant role in determining the coral health status by affecting the composition of the associated microbial community. Environmental stressful events and microbial infections may thus be superimposed to compromise immunity and trigger mortality outbreaks.
100 citations
TL;DR: It is suggested that pyelonephritis can be treated by reducing mitochondrial reactive oxygen species and thus by protecting mitochondrial integrity and lowering kidney damage, pointing to mitochondria as a therapeutic target.
Abstract: Acute pyelonephritis is a potentially life-threatening infection of the upper urinary tract. Inflammatory response and the accompanying oxidative stress can contribute to kidney tissue damage, resulting in infection-induced intoxication that can become fatal in the absence of antibiotic therapy. Here, we show that pyelonephritis was associated with oxidative stress and renal cell death. Oxidative stress observed in pyelonephritic kidney was accompanied by a reduced level of mitochondrial B-cell lymphoma 2 (Bcl-2). Importantly, renal cell death and animal mortality were both alleviated by mitochondria-targeted antioxidant 10(6′-plastoquinonyl) decylrhodamine 19 (SkQR1). These findings suggest that pyelonephritis can be treated by reducing mitochondrial reactive oxygen species and thus by protecting mitochondrial integrity and lowering kidney damage.
80 citations
TL;DR: This study provides the first evidence that infectious agents could be important in the population decline of this species, and highlights the need for further research into the route of entry of T. gondii organisms into the marine environment worldwide.
70 citations
TL;DR: The bibliometric approach applied in this study shows the evolution of research and identifies major gaps to be filled by future work on cyanotoxins that could potentially lead to the underestimation of the prevalence of toxic cyanobacterial blooms and the diversity of toxins worldwide.
52 citations
TL;DR: The effects of N‐[2‐(2‐methoxy‐6H‐dipyrido{2,3‐a:3,2‐e}pyrrolizin‐11‐yl)ethyl]‐2‐furamide (NMDPEF), a melatonin‐related inhibitor of quinone oxidoreductase2 (QR2) on the toxicity of PQ in vitro & in vivo are reported.
Abstract: BACKGROUND AND PURPOSE The mechanisms of paraquat (PQ)-induced toxicity are poorly understood and PQ poisoning is often fatal due to a lack of effective antidotes. In this study we report the effects of N-[2-(2-methoxy-6H-dipyrido{2,3-a:3,2-e}pyrrolizin-11-yl)ethyl]-2-furamide (NMDPEF), a melatonin-related inhibitor of quinone oxidoreductase2 (QR2) on the toxicity of PQ in vitro & in vivo. EXPERIMENTAL APPROACH Prevention of PQ-induced toxicity was tested in different cells, including primary pneumocytes and astroglial U373 cells. Cell death and reactive oxygen species (ROS) were analysed by flow cytometry and fluorescent probes. QR2 silencing was achieved by lentiviral shRNAs. PQ (30 mg·kg(-1)) and NMDPEF were administered i.p. to Wistar rats and animals were monitored for 28 days. PQ toxicity in the substantia nigra (SN) was tested by a localized microinfusion and electrocorticography. QR2 activity was measured by fluorimetry of N-benzyldihydronicotinamide oxidation. KEY RESULTS NMDPEF potently antagonized non-apoptotic PQ-induced cell death, ROS generation and inhibited cellular QR2 activity. In contrast, the cytoprotective effect of melatonin and apocynin was limited and transient compared with NMDPEF. Silencing of QR2 attenuated PQ-induced cell death and reduced the efficacy of NMDPEF. Significantly, NMDPEF (4.5 mg·kg(-1)) potently antagonized PQ-induced systemic toxicity and animal mortality. Microinfusion of NMDPEF into SN prevented severe behavioural and electrocortical effects of PQ which correlated with inhibition of malondialdehyde accumulation in cells and tissues. CONCLUSIONS AND IMPLICATIONS NMDPEF protected against PQ-induced toxicity in vitro and in vivo, suggesting a key role for QR2 in the regulation of oxidative stress.
48 citations
TL;DR: The silencing or inhibition of quinone oxidoreductase 2, a NAD(P)H‐independent flavoenzyme, was shown to significantly attenuate PQ toxicity in vitro, in primary pneumocytes and astroglial U373 cells, and to strongly antagonize PQ‐induced systemic toxicity and animal mortality.
Abstract: The use of the herbicide paraquat (1,1′-dimethyl-4,4′-bipyridylium dichloride; PQ) has been fiercely challenged due to its severe acute toxicity, putative neurotoxicity after long-term exposure and lack of antidotes. Breakthrough research on PQ is therefore required for an effective risk control and to allow a safer use of PQ in the future. The silencing or inhibition of quinone oxidoreductase 2, a NAD(P)H-independent flavoenzyme, was shown to significantly attenuate PQ toxicity in vitro, in primary pneumocytes and astroglial U373 cells, and to strongly antagonize PQ-induced systemic toxicity and animal mortality. The novel results reported in this issue of BJP, added to recent findings using sodium salicylate and lysine acetylsalicylate, in which full survival of PQ-intoxicated rats was also achieved, open the door for new preventative and therapeutic strategies that may lead to safer use of this effective pesticide.
47 citations
TL;DR: The data demonstrate that although it is very promising against African trypanosomes, cynaropicrin does not show efficacy compared to benznidazole in acute mouse models of T. cruzi infection.
Abstract: In vitro and in vivo activities against Trypanosoma cruzi were evaluated for two sesquiterpene lactones: psilostachyin A and cynaropicrin. Cynaropicrin had previously been shown to potently inhibit African trypanosomes in vivo, and psilostachyin A had been reported to show in vivo effects against T. cruzi, albeit in another test design. In vitro data showed that cynaropicrin was more effective than psilostachyin A. Ultrastructural alterations induced by cynaropicrin included shedding events, detachment of large portions of the plasma membrane, and vesicular bodies and large vacuoles containing membranous structures, suggestive of parasite autophagy. Acute toxicity studies showed that one of two mice died at a cynaropicrin dose of 400 mg/kg of body weight given intraperitoneally (i.p.). Although no major plasma biochemical alterations could be detected, histopathology demonstrated that the liver was the most affected organ in cynaropicrin-treated animals. Although cynaropicrin was as effective as benznidazole against trypomastigotes in vitro, the treatment (once or twice a day) of T. cruzi-infected mice (up to 50 mg/kg/day cynaropicrin) did not suppress parasitemia or protect against mortality induced by the Y and Colombiana strains. Psilostachyin A (0.5 to 50 mg/kg/day given once a day) was not effective in the acute model of T. cruzi infection (Y strain), reaching 100% animal mortality. Our data demonstrate that although it is very promising against African trypanosomes, cynaropicrin does not show efficacy compared to benznidazole in acute mouse models of T. cruzi infection.
33 citations
TL;DR: It is demonstrated that IVIBB is an effective and non-invasive way of monitoring bacterial dissemination in animals following pneumonic plague having strong correlation with cfu, and the reporter CO92-luc2 strain can be employed as a useful tool to monitor the efficacy of antimicrobial countermeasures in real time.
30 citations
TL;DR: This review will focus on the role of PRR in autophagy and its importance in maintaining cellular homeostasis and how its loss results in cell death will be essential for deciphering its role in physiology and pathology.
Abstract: The (pro)renin receptor (PRR) is a newly reported member of the renin-angiotensin system (RAS); a hormonal cascade responsible for regulating blood pressure. Originally, identification of PRR was heralded as the next drug target of the RAS, of which such therapies would have increased benefits against target-organ damage and hypertension. However, in the years since its discovery, several conditional knockout mouse models of PRR have demonstrated an essential role for this receptor unrelated to the RAS and blood pressure. Specific deletion of PRR in podocytes or cardiomyocytes resulted in the rapid onset of organ failure and subsequently animal mortality after only a matter of weeks. In both cell types, loss of PRR resulted in the intracellular accumulation of autophagosomes and misfolded proteins, indicating a disturbance in autophagy. In light of the fact that the majority of PRR is located intracellularly, this molecular function appears to be more relevant than its ability to bind to high, non-physiological concentrations of (pro)renin. This review will focus on the role of PRR in autophagy and its importance in maintaining cellular homeostasis. Understanding the link between PRR, autophagy and how its loss results in cell death will be essential for deciphering its role in physiology and pathology.
26 citations
TL;DR: The proposed framework for mortality estimation points to a unified framework for estimation of scavenging rates and searcher efficiency in a single trial and also allows estimation based only on accidental kills, obviating the need for carcass distribution trials.
Abstract: Carcass searches are a common method for studying the risk of anthropogenic hazards to wildlife, including nontarget poisoning and collisions with anthropogenic structures. Typically, numbers of carcasses found must be corrected for scavenging rates and imperfect detection. Parameters for these processes (scavenging and detection) are often estimated using carcass distribution trials in which researchers place carcasses in the field at known times and locations. In this manuscript I develop a variety of estimators based on multi-event or hidden Markov models for use under different experimental conditions. I apply the estimators to two case studies of avian mortality, one from pesticide exposure and another at wind turbines. The proposed framework for mortality estimation points to a unified framework for estimation of scavenging rates and searcher efficiency in a single trial and also allows estimation based only on accidental kills, obviating the need for carcass distribution trials. Results of the case studies show wide variation in the performance of different estimators, but even wider confidence intervals around estimates of the numbers of animals killed, which are the direct result of small sample size in the carcass distribution trials employed. These results also highlight the importance of a well-formed hypothesis about the temporal nature of mortality at the focal hazard under study.
20 citations
TL;DR: Preliminary results indicate a similar positive cardioprotective effect of drug injection into pericardial and pleural cavities under US guidance, demonstrating that this technique is useful for drug administration.
Abstract: Introduction: For the evaluation of the congestive heart failure (CHF) in rat models, the use of special equipment for echocardiography for dynamic evaluation is suggested. The optimal doxorubicin dose for CHF induction has still not been established. Aims: The aims of our study was to find a reliable doxorubicin CHF rat model using a general ultrasound (US) equipment for in vivo ultrasound examination of the systemic circulation, to establish the optimal doxorubicin dose, and to assess the feasibility of US guided administration of the drug. Material and methods: Sixty Wistar rats, weighing 180-200 g were assigned to 3 groups (n=20 in each): group A - 4 time intraperitoneal doxorubicin “Sigma”administration, cumulative dose 2.49 mg/animal or 12.45 mg/kg; group B and 5 time doxorubicin administration, cumulative dose 3.03 mg/animal or 15.15 mg/kg; and group C- controls (injected same volume of saline). Dynamic US using linear 12 MHz transducer was used to establish the CHF modifications. Two rats with CHF were injected under US guidance in the pleural cavity with 0.06 ml cardiotropic drug levosimendan and two rats in the pericardial cavity. Results: We established the optimal cumulative doxorubicin dose for CHF induction at 12.45 mg/kg. At a higher dose, more than 40% of animals died. A lower dose did not induce significant clinical and US CHF criteria. Congestion (followed by weight gain) led to lower animal mortality. Preliminary results indicate a similar positive cardioprotective effect of drug injection into pericardial and pleural cavities under US guidance, demonstrating that this technique is useful for drug administration. Conclusions: US is an effective modality for in vivo monitoring of the rat organs for the study of cardiovascular function or for drug administration under US guidance. Suggested model (optimal dose of doxorubicin for simulation of CHF of 2.5 mg/animal, a cumulative dose of 12.45 mg/kg in 4 injections every 3 days) can be used for research purposes.
TL;DR: In this article, a 9 km stretch of National Highway-7 passing through Pench Tiger Reserve in central India with an objective to assess impacts of road induced habitat reduction and animal mortality pose the greatest challenge of conserving wildlife species in protected areas.
Abstract: Road induced habitat reduction and animal mortality pose the greatest challenge of conserving wildlife species in protected areas with extensive road networks. This study was conducted in a 9 km stretch of National Highway-7 passing through Pench Tiger Reserve in central India with an objective to assess impacts on wildlife species and their habitats. Considering that snakes are a vital part of food webs of every ecosystem and are more susceptible to vehicular causalities, we present the ecological impacts of the highway on snakes in this Tiger Reserve. We surveyed this highway section for a total of 430 road cruising days spread equally across three seasons and over two years from August 2008 to July 2010. We collected data on different variables influencing use of road side habitat, the road surface and the factors influencing mortality of snakes. We recorded a total of 490 snake road kills (approx.1.13 snakes/10km/day) during the study. We recorded the highest mortality (50%) of snakes during monsoon. Barred wolf snake had the highest mortality (22%) followed by Common cat snake (11%) and Striped keel back (8%). We identified fatality hotspots in different sections of the highway using Kernel Density Method. The linear regression model showed that the road kills were positively related to high elevation and negatively related to proximity of the agriculture fields, animal crossings and water sources.
TL;DR: A kindling TLE model in rhesus monkeys representing a primate animal model of epileptogenesis was established for the first time using repeated intramuscular injections of Coriaria lactone and resulted in behavioral, electrographical, and anatomical characteristics of human TLE.
TL;DR: Analysis of reverse transcription PCR products showed that human recombinant erythropoietin adsorbed on poly(butyl)cyanoacrylate nanoparticles more than 2-fold increased the expression of BDNF and NGF neurotrophins in the rat brain frontal cortex and hippocampus.
Abstract: Human recombinant erythropoietin adsorbed on poly(butyl)cyanoacrylate nanoparticles and administered intraperitoneally in a dose of 0.05 mg/kg exhibited a neuroprotective effect in experimental intracerebral posttraumatic hematomas (hemorrhagic stroke) and reduced animal mortality. Human recombinant erythropoietin, native and adsorbed on lactic and glycolic acid copolymer-based nanoparticles, exhibited no antistroke effect on this model. Analysis of reverse transcription PCR products showed that human recombinant erythropoietin adsorbed on poly(butyl)cyanoacrylate nanoparticles more than 2-fold increased the expression of BDNF and NGF neurotrophins in the rat brain frontal cortex and hippocampus.
TL;DR: A disease outbreak among juvenile cobia farmed in cages in the state of Rio de Janeiro, Brazil, caused by the dinoflagellate Amyloodinium ocellatum and the monogenean Neobenedenia melleni was reported.
Abstract: This study reports a disease outbreak among juvenile cobia (Rachycentron canadum) farmed in cages in the state of Rio de Janeiro, Brazil, caused by the dinoflagellate Amyloodinium ocellatum and the monogenean Neobenedenia melleni. Two thousand five hundred fish were stocked at 0.4 kg/m3 in a set of 12 m3 tanks, in autumn (mean weight 15.0 ± 7.3 g) and in winter (mean weight 43.0 ± 5.6 g). Freshwater baths were administered as a routine treatment, as the symptoms were detected followed by two collection samples. Firstly in May 2011 (n = 5) and secondly in September 2011 (n = 10). In the first sample, the prevalence of N. melleni on the body surface was 100% and the mean intensity was 42.0 ± 1.7, while in the second sample the prevalence was 60% with a mean intensity 3.0 ± 0.2 and mean abundance 1.8 ± 0.4. Amyloodinium ocellatum was only found in the second sample, at a prevalence 100% and mean intensity 46.8 ± 3.4. The cause of fish mortality was possibly associated with a decrease in fish resistance after the first contact with monogenean parasites, allied with respiratory difficulty caused by the presence of A. ocellatum in the gills.
TL;DR: Rec recombinant gE produced in baculovirus-infected insect cells is a viable source of antigen for the detection of SHV-1 in ELISA tests and is used to develop a local indirect ELISA test with sensitivity and specificity comparable to currently available commercial tests.
TL;DR: The results suggested that Kupffer cells, TNF-α and TLR-4 play central mediator roles during the hepatoprotection against PEA-induced hepatotoxicity conferred by LPS.
Abstract: Context: Liver injury can be induced by various hepatotoxicants, including Pseudomonas aeruginosa exotoxin A (PEA). Our previous study indicated that PEA-induced rat hepatotoxicity was T cells and Kupffer cells dependent. Several reports have demonstrated that non-toxic doses of bacterial lipopolysaccharide (LPS) can protect liver against the chemicals-induced toxicity such as acetaminophen and concanavalin-A.Objective: This study aimed to investigate the protecting mechanisms of LPS on PEA-induced hepatotoxicity.Results: Rats pretreated with LPS (40 μg/kg, 12 h before PEA admission) significantly decreased animal mortality, serum enzyme (ALT, AST and T-bil) activities, histopathological changes and hepatocytes apoptosis following challenge with PEA. The concentrations of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ) and interleukin-2 (IL-2) were reduced, but IL-6 and IL-10 were increased in the serum. In addition, prior treatment of these LPS-pretreated rats with gadolinium chlori...
TL;DR: Xymedon (1-(β-oxyethyl)-4,6-dimethyl-1,2-dihydro-2-oxopyrimidine), a regeneratory and wound-healing drug, exhibited hepatoprotective activity in laboratory animals with experimental toxic hepatitis as mentioned in this paper.
Abstract: Xymedon (1-(β-oxyethyl)-4,6-dimethyl-1,2-dihydro-2-oxopyrimidine), a regeneratory and wound-healing drug, exhibited hepatoprotective activity in laboratory animals with experimental toxic hepatitis. Oral drug reduced the severity of toxic involvement of the liver induced by CCl4 and reduced animal mortality. Xymedon promoted recovery of the blood biochemical parameters characterizing the liver status.
01 Apr 2013
TL;DR: In this article, the utility of in-vessel composting for animal mortality management at the Virginia Department of Transportation (VDOT) was evaluated using rotary drum and forced aeration bin systems.
Abstract: The Virginia Department of Transportation (VDOT) removes an estimated 55,000 deer carcasses from its roadways each year at a cost of more than $4 million per year. Many VDOT maintenance facilities have a need for viable, environmentally compliant, and cost-effective carcass management strategies. Disposal challenges include a decreasing availability of conventional disposal methods, such as landfills, and a lack of viable burial areas. The purpose of this study was to evaluate two in-vessel composting systems to determine the utility of each as a carcass management option for VDOT. The systems were a rotary drum system and a forced aeration bin system (forced air system). Pilot projects were conducted to determine the utility of each system based on two factors: (1) whether the generated compost met a set of established composting criteria, including regulatory standards; and (2) whether the system performed well from an operational standpoint. A rotary drum system was installed at a VDOT maintenance facility and monitored for 163 days. The generated compost met the established pathogen destruction criteria but was inconsistent with regard to meeting the temperature and moisture criteria. The operational performance of the system was also inconsistent. The problems encountered may be preventable in future installations, but the system requires further evaluation to determine its utility as a means of animal mortality management for VDOT. It is recommended that VDOT install a smaller rotary drum system at a selected maintenance facility and evaluate its performance when the lessons learned described in this study are applied. A forced air system was installed at another VDOT maintenance facility and monitored for 274 days. The generated compost met all established compost criteria (i.e., temperature, compost maturity, and pathogen destruction), and the system performed well from an operational standpoint. This system is a useful means of animal mortality management for VDOT. It is recommended that VDOT install several additional forced air system units at maintenance areas interested in this method of composting. When the savings in disposal fees and travel costs from composting mortalities in a compost vessel rather than disposing of them at a facility are taken into account, the initial investment in a compost vessel would be offset in less than 5 years for maintenance facilities with particularly long drives to a disposal facility (25 to 40 miles). This study will be followed by an in-depth study to evaluate the economics and logistics of in-vessel composting to complete the feasibility analysis of this method of animal mortality management for VDOT. A composting guidance document will also be prepared to support the implementation of animal mortality composting at VDOT maintenance facilities.
TL;DR: Virus retention tests showed that DCs retain AI viruses safely inside, and DCs are effective tools for evaluating virus inactivation within animal manure and mortality disposal systems.
TL;DR: The ability of sevoflurane to modulate sepsis-induced organ injury and survival, whether given during CLP and for 2 hr afterwards or when given at a lower dose for 30 minutes 24 hrpost-CLP exposure, is interesting.
Abstract: To the clinician, volatile anesthetics are the means by which we render patients insensitive to pain, still, and unaware/amnestic. To the molecular pharmacologist, they are the object of an ongoing search for mechanism(s) of action. To the laboratory investigator, they are a tool for rendering animals anesthetized in order to perform various experimental procedures. From a clinical perspective we often view volatile anesthetics and their effects as benign, reversible, and temporary. Or are they?
In this issue of Anesthesiology, Herrmann et al report the effects of volatile anesthetics in a murine model of sepsis.1 They used a common approach, cecal ligation and puncture (CLP), in which the cecum is tied off, and punctured with a needle in a standard fashion so as to leak intestinal contents into the peritoneum, which then causes sepsis in a reproducible model. Animals were anesthetized during surgery and for 2 hrpost-operatively with 1.2 minimal alveolar concentration (MAC) of desflurane, isoflurane or sevoflurane (termed “conditioning” by the authors). A sham (control) group of animals underwent laparotomy under ketamine anesthesia without CLP. Outcome assessments included 7d survival, renal and hepatic function, bacterial load in blood and peritoneal fluid, and cytokine concentrations in plasma and peritoneal fluid. In a second series of experiments, the original CLP was performed under ketamine anesthesia, and the animals were anesthetized 24 hr later with sevoflurane or desflurane, to determine the effects of volatile anesthetics after initiation of sepsis (termed “postconditioning” by the authors).
When administered using the first (conditioning) regimen, 7d survival significantly increased from 17% in controls to 83% and 58% after sevoflurane and desflurane, respectively, but was not significantly increased by isoflurane (42%). When administered 24 hr after CLP (postconditioning), sevoflurane (1 MAC for 0.5hr) significantly increased survival to 66%, but neither desflurane (1 MAC for 0.5hr) nor a greater sevoflurane exposure (1.2 MAC for 2 hr) increased survival. In the first experiment, sevoflurane partially prevented renal and hepatic dysfunction (evidenced by lesser increases in blood urea nitrogen and hepatic enzymes such as transaminases). It did not reduce bacterial load in peritoneal fluid and blood or alter levels of interleukin-6 or monocyte chemoattractant protein-1in plasma and peritoneal fluid.
The ability of sevoflurane to modulate sepsis-induced organ injury and survival, whether given during CLP and for 2 hr afterwards or when given at a lower dose for 30 minutes 24 hrpost-CLP exposure, is interesting. So also is the ability of desflurane during CLP and for 2 hr afterwards (but not at 24 hr), and the lesser ability of isoflurane using the same strategy. And with these new observations come the natural questions: (1) what is the mechanism, (2) why are the anesthetics different with regard to their conditioning effects, and (3) why is sevoflurane but not desflurane effective in a postconditioning regimen? Unfortunately, the report by Herrmann et al raises more questions than it answers.
Given that animal mortality in sepsis is highly dependent upon both sex and strain, it is unclear whether these results would be generalizable to either female mice or either outbred or other commonly used inbred strains. There is also increasing recognition that mortality continues up to 28 days following CLP,2 and the impact of volatile anesthetics on late deaths from sepsis was not evaluated in the experiments reported by Herrmann et al. Further, the investigators did not give animals postoperative antibiotics, a common practice following CLP in order to enhance clinical relevance. It is known that antibiotics improve survival after CLP, and it is not clear whether the survival advantage conferred by volatile anesthetics would persist in either a lower mortality model or one with a lower bacterial burden. It is also questionable whether the modest differences in blood urea nitrogen and transaminases are sufficient to account for the profound survival advantage conferred by sevoflurane, especially given the absence of differences in bacteremia, local infection or pro-inflammatory cytokines. Sepsis is associated with chronic immunosuppression and modulating the immune system represents a potential therapeutic avenue in the disease. Given the fact that volatile anesthetics can have immunomodulatory effects, assaying the immune system represents a logical next step. Additionally, the investigators only evaluated biochemical outcomes after sevoflurane but not isoflurane or desflurane exposure, and not when started 24 hr after CLP. They also did not evaluate differences between the drugs. Are desflurane and isoflurane less effective because they undergo less metabolism?3
We also do not know if the effects of differing anesthetics are additive. This is possible in light of a recent study of two different models of critical illness examining the impact of giving ketamine prior to the induction of sevoflurane anesthesia.4 Survival was improved in mice that received ketamine 10 minutes prior to anesthesia with sevoflurane that were given an LPS challenge immediately after laparotomy compared to mice given sevoflurane alone although ketamine had no impact on survival in mice given Escherichia coli after a laparotomy. This study design differed from that of Herrmann et al. in both the anesthetic strategies and models of critical illness used; however, it raises the possibility that unique anesthetics given at different times could potentially alter the host immune response thereby improving survival.
While a number of questions remain, we can now add the survival benefit conferred by sevoflurane and desflurane following CLP to prior examples of protection by volatile anesthetics against injury from cerebral, cardiac, hepatic, and renal ischemia-reperfusion, and by isoflurane against a comparable model of CLP sepsis.5 A mechanistic understanding of how volatile anesthetics improve rodent survival in models of sepsis and ischemia-reperfusion may thus yield new exciting therapeutic avenues to pursue in critically ill patients. And additionally, mechanistic questions aside, and of immediate relevance to experimentalists using volatile anesthetics to enable their animal procedures, is that these drugs may not be the benign, temporary, and reversible tools they might be considered to be. As identified by Herrmann et al, anesthesia may be a critical confounder when comparing study data where different anesthetic protocols were used.
TL;DR: This modified animal model could be contributive in the evaluation of antibacterial agents, especially to simulate the behavior of intensive care unit immunocompromised patients.
Abstract: Because the magnitude of spontaneous bacterial clearance can be similar or even higher than treatment effect, depending upon experimental model and bacterial strain used, this work investigated the value of rendering rats immunosuppressed to facilitate bacterial implantation and reduce spontaneous bacterial clearance. In a first step, rats received a single intravenous cyclophosphamide dose 4 days before infection. Three different doses were tested: 10, 20, and 40 mg/kg. After modeling with NONMEM V, the cyclophosphamide dose required to maintain white blood cell count <1.0 × 10(3)/μL from day 4 to day 5 was 30 mg/kg. In a second step, influence of immunosuppression on lung bacterial titers was characterized. Rats were given one of the three intravenous cyclophosphamide doses (0, 10, 30 mg/kg), and after 4 days, they were infected by tracheal injection of 8.9 ± 0.1 log10 cfu Enterobacter cloacae before being sacrificed at different times. Bacteria in homogenized lungs were quantitatively cultured on Drigalski agar. Bacterial lung count was closely influenced by the grade of induced leukopenia. A single intravenous 30 mg/kg cyclophosphamide dose 4 days before infection suppressed the spontaneous clearance of E. cloacae for at least 30 h without significantly increasing animal mortality; this result seems to be linked to a white blood cell count maintained lower than 1.0 × 10(3)/μL for all the time. This modified animal model could be contributive in the evaluation of antibacterial agents, especially to simulate the behavior of intensive care unit immunocompromised patients.
TL;DR: The study showed that diseases can be controlled and income could be improved if inputs and credit are provided in the areas of concern and the after effects of the study resulted in improved managemental practices which caused remarkable development.
Abstract: 3 Abstract: A study was conducted to examine the effect of Aga Khan Rural Support Program on huma n resource development particularly on livestock management in district Chitral. Study was conducted in three- community organizations in village Charun, Tehsil Mastu, Chitral. A total 120 respondents were randomly selected for interview, 98 beneficiaries and 22 non-beneficia ries. Almost 100% respondents were landowners, cultivating a land of about two kanal and were satisfied with training component of AKRSP , about 47% were literate. The enrolled respondents were 50.2% of the age 33-45 years and 30.1% of the age 46-58 years. Farming was main occupation of 64% beneficiaries, 29% adopted as secondary occupation and 8% having not even the secondary occupation. The rest were engaged in other services like business, labor etc., while majority having annual income ranging from RS. 34600 to 45600. About 45% respondents applied training information and found it useful. Collectively observed 47% increase in livestock size and 24%-improved breed was used as AKRSP had provided a jersey bull for crossing with local breed. The after effects of the study resulted in improved managemental practices which caused remarkable development like enhanced production and increased income of the beneficiaries i.e. up to 62%, changes in farmin g practice up to 19% and up gradation in occupation of 65% beneficiaries. Besides improvement in the size of livestock holding and milk production, medication and vaccination reduced animal mortality and disease out breaks. The study showed that diseases can be controlled and income could be improved if inputs and credit are provided in the areas of concern.
01 Jan 2013
TL;DR: The intestinal damage had improved significantly in the experiment groups that received different reference drugs which is comparable with sulfasalazine treated group, and the experimental observations, gross pathology of intestinal lesions and statistical analysis reveals no significant difference among the different reference drug treated groups.
Abstract: Crohn's disease and Ulcerative colitis were chronic inflammatory disorders of the bowel categorized as inflammatory bowel diseases. Trinitrobenzene sulfonic acid (TNBS)-induced colitis was one of the most common methods for studying inflammatory bowel disease in animal models. Several factors may, however, affect its reproducibility, rate of animal mortality, and macroscopic and histopathological outcomes.The current study was undertaken with the objective to validate the main contributing factors to this method and compare the effects of different reference drugs upon better amelioration of trinitrobenzenesulfonic acid (TNBS) induced colitis. With the above objectives, ulcerative colitis was induced by intrarectal administration of TNBS in male Wistar rats at a dose rate of 20 mg in 0.5 mL of ethanol per animal for all groups except the negative control group, which received 0.5 mL of normal saline. Different reference drugs like dexamethasone (1 mg/kg, intraperitoneally (i.p.) and 2 mg/kg, orally (p.o.)), hydrocortisone acetate (20 mg/kg, i.p.; 20 mg/kg, enema) and sulfasalazine 500mg/kg ,p.o.were administered daily once from Day 3 to 9 except the negative and positive controls which received normal saline at the rate of 10 mL/kg body weight. All the animals were sacrificed on Day 10; the colons were excised and the colon morphology and net weight of the colon segment were graded and measured, respectively. The intestinal damage had improved significantly in the experiment groups that received different reference drugs which is comparable with sulfasalazine treated group. The experimental observations, gross pathology of intestinal lesions and statistical analysis reveals no significant difference among the different reference drugs treated groups. Keywords: Reference drugs, trinitrobenzenesulfonic acid, Hydrocortisone, Dexamethasone, Sulfasalazine