Trombocyters roll i immunförsvaret vid lunginflammation

Thrombocytopenia is a common feature in severe infection and the extent of the thrombocytopenia has been correlated to the clinical prognosis. However the pathophysiology behind this phenomenon is not completely understood. Research in the last decade has shown that thrombocytes possess several antimicrobial properties, suggesting that they might play a still unknown role in innate immunity. Moreover platelets are known to sequestrate out into lung tissue in response to stimuli like lipopolysaccharide (LPS) and septicaemia. Streptococcus pneumoniae is a common cause of severe community aquired pneumonia and septicaemia. In this project I show that platelets in vitro are activated by S. pneumoniae and can release antimicrobial peptides in response to thrombin. This occurs independent of interactions with other cells. In vivo, I show that platelet deficiency results in increased bacterial numbers within the lungs in a mouse model of S. pneumoniae pneumonia. Histopathological examination of the lungs indicates that platelets co-localise with the bacteria –and may "trap" them within lung tissue. I conclude that platelets contribute to innate immunity to S. pneumoniae pneumonia identifying a potential therapeutic target for patients with severe infection.Trombocytopeni är en vanlig företeelse i samband med svår infektion och graden av trombocytopeni hos akut sjuka patienter har visats vara korrelerad till klinisk prognos. Detta till trots är patofysiologin till detta fenomen ännu inte helt kartlagd. Det senaste årtiondets forskning har visat att trombocyter utöver sina uppgifter i koagulationen även äger flera antimikrobiska egenskaper vilket väckt frågan om trombocyter också spelar en ännu okänd roll i det cellmedierade immunförsvaret. Det har även visats att trombocyter som utsätts för stimuli som lipopolysaccharider (LPS) och septikemi sequestrerar ut i lungvävnad in vivo. Streptococcus pneumoniae är en vanlig etiologisk orsak till förvärvad pneumoni och septikemi. I detta arbete visar jag att trombocyter in vitro blir aktiverade av S. pneumoniae och frigör antimikrobiska substanser mot S. pneumoniae efter trombin stimulering, detta utan interaktioner från andra celler. In vivo visar jag att trombocytopeni under infektion leder till en snabbare bakteriell tillväxt i lungorna på möss i en modell av S. pneumoniae infektion. Histopatologisk undersökning av dessa lungor indikerar att trombocyter samlokaliserar med bakterier –och därmed eventuellt fångar bakterier i lungvävnad innan kolonisation av vävnad hinner ske. Slutsatsen är att trombocyter medverkar i det cellmedierade immunförsvaret mot S. pneumoniae pneumoni vilket potentiellt kan utgöra ett terapeutiskt mål för patienter med svår infektion

Alpha-chloralose poisoning in cats: clinical findings in 25 confirmed and 78 suspected cases

Objectives The aim of this study was to describe the clinical picture in cats with alpha-chloralose (AC) intoxication and to confirm AC in serum from suspected cases of AC poisoning. Methods Suspected cases of AC poisoning were identified in patient records from a small animal university hospital from January 2014 to February 2020. Clinical signs of intoxication described in respective records were compiled, the cats were graded into four intoxication severity scores and hospitalisation time and mortality were recorded. Surplus serum from select cases in late 2019 and early 2020 was analysed to detect AC with a quantitative ultra-high performance liquid chromatography tandem mass spectrometry analysis, and the AC concentration was compared with the respective cat's intoxication severity score. Results Serum from 25 cats was available for analysis and AC poisoning was confirmed in all. Additionally, 78 cats with a clinical suspicion of AC intoxication were identified in the patient records, most of which presented from September to April. The most common signs of intoxication were ataxia, tremors, cranial nerve deficits and hyperaesthesia. The prevalence of clinical signs and intoxication severity differed from what has previously been reported, with our population presenting with less severe signs and no deaths due to intoxication. The majority had a hospitalisation time <48 h, irrespective of intoxication severity score. Conclusions and relevance This study describes the clinical signs and prognosis in feline AC intoxication. There were no mortalities in confirmed cases, indicating that AC-poisoned cats have an excellent prognosis when treated in a timely manner. Recognition of AC intoxication as a differential diagnosis for acute onset of the described neurological signs in areas where AC exposure is possible may influence clinical decision-making and help avoid excessive diagnostic procedures. A severe clinical picture upon presentation could be misinterpreted as a grave prognosis and awareness about AC poisoning may avoid unnecessary euthanasia

Development and Validation of a Quantitative UHPLC-MS-MS Method for the Determination of Alpha-Chloralose in Feline Blood and Application on Blood Samples Collected from Cats with Symptoms of Alpha-Chloralose Poisoning

Alpha-chloralose (AC) is used as a rodenticide as well as an anesthetic agent in laboratory animals. It was previously also used as an avicide. Detection of AC in blood samples or in body tissues collected postmortem is key for the diagnosis of clinical cases and a requirement for surveillance of secondary toxicosis, including potential cases in wild animals. Reports on poisoning of humans and non-laboratory animals confirmed by the detection of AC or its metabolites are available, however poisoning of domestic animals are rarely available. Furthermore, reports on clinical cases in domestic animals rarely report quantifications of AC in blood or body tissues. The present study describes the validation of a quantitative Ultrahigh Performance Liquid Chromatography tandem Mass Spectrometry (UHPLC-MS-MS) method that can be used in cases of suspected AC poisoning in cats. The validation study showed the method to be fit for purpose. In serum, the limit of quantification was 100 ng/mL and the limit of detection was 30 ng/mL. The new analytical method was applied on blood samples collected from 20 individual cats with a preliminary clinical diagnosis of acute AC poisoning. AC was confirmed in all 20 feline blood samples, and the concentration range of AC was 538-17,500 ng/mL. The quantitative method developed in this study was found to be a fast and selective method for confirmation of AC poisoning using blood samples from cats

Alpha-chloralose poisoning in cats : clinical findings in 25 confirmed and 78 suspected cases

Objectives The aim of this study was to describe the clinical picture in cats with alpha-chloralose (AC) intoxication and to confirm AC in serum from suspected cases of AC poisoning. Methods Suspected cases of AC poisoning were identified in patient records from a small animal university hospital from January 2014 to February 2020. Clinical signs of intoxication described in respective records were compiled, the cats were graded into four intoxication severity scores and hospitalisation time and mortality were recorded. Surplus serum from select cases in late 2019 and early 2020 was analysed to detect AC with a quantitative ultra-high performance liquid chromatography tandem mass spectrometry analysis, and the AC concentration was compared with the respective cat's intoxication severity score. Results Serum from 25 cats was available for analysis and AC poisoning was confirmed in all. Additionally, 78 cats with a clinical suspicion of AC intoxication were identified in the patient records, most of which presented from September to April. The most common signs of intoxication were ataxia, tremors, cranial nerve deficits and hyperaesthesia. The prevalence of clinical signs and intoxication severity differed from what has previously been reported, with our population presenting with less severe signs and no deaths due to intoxication. The majority had a hospitalisation time &lt;48 h, irrespective of intoxication severity score. Conclusions and relevance This study describes the clinical signs and prognosis in feline AC intoxication. There were no mortalities in confirmed cases, indicating that AC-poisoned cats have an excellent prognosis when treated in a timely manner. Recognition of AC intoxication as a differential diagnosis for acute onset of the described neurological signs in areas where AC exposure is possible may influence clinical decision-making and help avoid excessive diagnostic procedures. A severe clinical picture upon presentation could be misinterpreted as a grave prognosis and awareness about AC poisoning may avoid unnecessary euthanasia

Development and Validation of a Quantitative UHPLC-MS-MS Method for the Determination of Alpha-Chloralose in Feline Blood and Application on Blood Samples Collected from Cats with Symptoms of Alpha-Chloralose Poisoning

Alpha-chloralose (AC) is used as a rodenticide as well as an anesthetic agent in laboratory animals. It was previously also used as an avicide. Detection of AC in blood samples or in body tissues collected postmortem is key for the diagnosis of clinical cases and a requirement for surveillance of secondary toxicosis, including potential cases in wild animals. Reports on poisoning of humans and non-laboratory animals confirmed by the detection of AC or its metabolites are available, however poisoning of domestic animals are rarely available. Furthermore, reports on clinical cases in domestic animals rarely report quantifications of AC in blood or body tissues. The present study describes the validation of a quantitative Ultrahigh Performance Liquid Chromatography tandem Mass Spectrometry (UHPLC-MS-MS) method that can be used in cases of suspected AC poisoning in cats. The validation study showed the method to be fit for purpose. In serum, the limit of quantification was 100 ng/mL and the limit of detection was 30 ng/mL. The new analytical method was applied on blood samples collected from 20 individual cats with a preliminary clinical diagnosis of acute AC poisoning. AC was confirmed in all 20 feline blood samples, and the concentration range of AC was 538-17,500 ng/mL. The quantitative method developed in this study was found to be a fast and selective method for confirmation of AC poisoning using blood samples from cats

Alpha-chloralose poisoning in cats in three Nordic countries - the importance of secondary poisoning

Background Alpha-chloralose (AC) is a compound known to be toxic to various animal species and humans. In 2018 and 2019 an increase in suspected cases of AC poisoning in cats related to the use of AC as a rodenticide was reported to national veterinary and chemical authorities in Finland, Norway and Sweden by veterinarians working in clinical practices in respective country. The aims of this study were to prospectively investigate AC poisoning in cats, including possible secondary poisoning by consuming poisoned mice, and to study metabolism and excretion of AC in cats through analysis of feline urine. Methods Data on signalment, history and clinical findings were prospectively collected in Finland, Norway and Sweden from July 2020 until March of 2021 using a questionnaire which the attending veterinarian completed and submitted together with a serum sample collected from suspected feline cases of AC-poisoning. The diagnosis was confirmed by quantification of AC in serum samples. Content of AC was studied in four feline urine samples, including screening for AC metabolites by UHPLC-HRMS/MS. Bait intake and amount of AC consumed by mice was observed in wild mice during an extermination of a rodent infestation. Results In total, 59 of 70 collected questionnaires and accompanying serum samples were included, with 127 to 70 100 ng/mL AC detected in the serum. Several tentative AC-metabolites were detected in the analysed feline urine samples, including dechlorinated and oxidated AC, several sulfate conjugates, and one glucuronic acid conjugate of AC. The calculated amount of AC ingested by each mouse was 33 to 106 mg with a mean of 61 mg. Conclusions Clinical recognition of symptoms of AC poisoning in otherwise healthy cats roaming free outdoors and known to be rodent hunters strongly correlated with confirmation of the diagnosis through toxicological analyses of serum samples. The collected feline exposure data regarding AC show together with the calculation of the intake of bait and subsequent AC concentrations in mice that secondary poisoning from ingestion of mice is possible. The results of the screening for AC metabolites in feline urine confirm that cats excrete AC both unchanged and metabolized through dechlorination, oxidation, glucuronidation and sulfatation pathways

Alpha-chloralose poisoning in cats in three Nordic countries : the importance of secondary poisoning

Background Alpha-chloralose (AC) is a compound known to be toxic to various animal species and humans. In 2018 and 2019 an increase in suspected cases of AC poisoning in cats related to the use of AC as a rodenticide was reported to national veterinary and chemical authorities in Finland, Norway and Sweden by veterinarians working in clinical practices in respective country. The aims of this study were to prospectively investigate AC poisoning in cats, including possible secondary poisoning by consuming poisoned mice, and to study metabolism and excretion of AC in cats through analysis of feline urine. Methods Data on signalment, history and clinical findings were prospectively collected in Finland, Norway and Sweden from July 2020 until March of 2021 using a questionnaire which the attending veterinarian completed and submitted together with a serum sample collected from suspected feline cases of AC-poisoning. The diagnosis was confirmed by quantification of AC in serum samples. Content of AC was studied in four feline urine samples, including screening for AC metabolites by UHPLC-HRMS/MS. Bait intake and amount of AC consumed by mice was observed in wild mice during an extermination of a rodent infestation. Results In total, 59 of 70 collected questionnaires and accompanying serum samples were included, with 127 to 70 100 ng/mL AC detected in the serum. Several tentative AC-metabolites were detected in the analysed feline urine samples, including dechlorinated and oxidated AC, several sulfate conjugates, and one glucuronic acid conjugate of AC. The calculated amount of AC ingested by each mouse was 33 to 106 mg with a mean of 61 mg. Conclusions Clinical recognition of symptoms of AC poisoning in otherwise healthy cats roaming free outdoors and known to be rodent hunters strongly correlated with confirmation of the diagnosis through toxicological analyses of serum samples. The collected feline exposure data regarding AC show together with the calculation of the intake of bait and subsequent AC concentrations in mice that secondary poisoning from ingestion of mice is possible. The results of the screening for AC metabolites in feline urine confirm that cats excrete AC both unchanged and metabolized through dechlorination, oxidation, glucuronidation and sulfatation pathways

Alpha-chloralose poisoning in cats : Nordic Report highlights the risk of poisoning to non-target species

This report provides results from studies of Alphachloralosis poisoning in cats in three Nordic countries. A publication by Windahl et al. (2022) is the main scientific foundation to the report. The aim of this study was to investigate the possibility of secondary AC poisoning in cats from consuming poisoned mice, and to study metabolism and excretion of AC in cats. Findings in studies highlighted in the report showed that secondary poisoning of cats from ingestion of mice is possible and highlights the risk of AC poisoning to non-target species. Observations of wild mice revealed that they can consume significantly more AC-containing bait than earlier presumed.

Evaluation of cardiac troponin I as a predictor of death in critically ill cats

Abstract Background Abnormally high serum cardiac troponin I (cTnI) concentration, reflecting leakage from or necrosis of cardiomyocytes, is a negative prognosticator for death in dogs. Objectives To investigate in critically ill cats whether serum cTnI concentration is abnormally high, identify conditions associated with abnormally high cTnI concentrations, and evaluate cTnI as an independent prognosticator for death and a potential coprognosticator to the acute patient physiologic and laboratory evaluation (APPLE) score in cats. Animals One hundred nineteen cats admitted to intensive care units (ICU) and 13 healthy cats at 2 university teaching hospitals. Methods Prospective study. Clinical examinations were performed, APPLE scores calculated, and serum cTnI and serum amyloid A (SAA) measured within 24 hours after admission. Outcome was defined as death/euthanasia or survival to discharge, 28 and 90 days after ICU‐admission. Prognostic capacity of cTnI, APPLE scores and models combining cTnI and scores were evaluated by receiver‐operator‐characteristic analyses. Results Median (IQR) serum cTnI concentration was higher in ill (0.63 [0.18‐2.65] ng/mL) compared to healthy (0.015 [0.005‐0.041] ng/mL) cats (P 5 mg/L (0.84 [0.23‐2.81] ng/mL; P = .009) than in cats without these characteristics (0.45 [0.12‐1.70] and 0.35 [0.015‐0.96] ng/mL). The in‐hospital case fatality rate was 29%. Neither serum cTnI concentration for all critically ill cats (area‐under‐the‐curve 0.567 [95% CI 0.454‐0.680], n = 119) or subgroups (0.625 [0.387‐0.863], n = 27; 0.506 [0.360‐0.652], n = 86), nor APPLE scores (fast 0.568 [0.453‐0.682], full 0.585 [0.470‐0.699], n = 100), were significant prognosticators for death. Conclusions and Clinical Importance Abnormally high serum cTnI concentration was common in critically ill cats. Unlike in dogs, cTnI did not confer prognostic information regarding death