Markers Of Organ Damage Research Articles

What are the risk factors for ascending aorta dilatation in the non-diabetic normotensive population? A cross-sectional study in China

ObjectivesAscending aorta dilatation (AAD) has been suggested as a surrogate marker for vascular organ damage in the hypertensive population. However, limited data are available on AAD in normotensive individuals. This...

Protective effects of nordalbergin against LPS-induced endotoxemia through inhibiting MAPK/NF-κB signaling pathway, NLRP3 inflammasome activation, and ROS production.

Nordalbergin is a coumarin extracted from Dalbergia sissoo DC. To date, the biological effects of nordalbergin have not been well investigated. To investigate the anti-inflammatory responses and the anti-oxidant abilities of nordalbergin using lipopolysaccharide (LPS)-activated macrophages and LPS-induced sepsis mouse model. Production of nitrite oxide (NO), prostaglandin E2 (PGE2), pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β), reactive oxygen species (ROS), tissue damage and serum inflammatory markers, and the activation of the NLRP3 inflammasome were examined. Our results indicated that nordalbergin reduced the production of NO and pro-inflammatory cytokines in vitro and ex vivo. Nordalbergin also suppressed iNOS and cyclooxygenase-2 expressions, decreased NF-κB activity, and attenuated MAPKs signaling pathway activation by decreasing JNK and p38 phosphorylation by LPS-activated J774A.1 macrophages. Notably, nordalbergin diminished NLRP3 inflammasome activation via repressing the maturation of IL-1β and caspase-1 and suppressing ROS production by LPS/ATP- and LPS/nigericin-activated J774A.1 macrophages. Furthermore, nordalbergin exhibited protective effects against the infiltration of inflammatory cells and also inhibited the levels of organ damage markers (AST, ALT, BUN) by LPS-challenged mice. Nordalbergin possesses anti-inflammatory effects in macrophage-mediated innate immune responses, alleviates ROS production, decreases NLRP3 activation, and exhibits protective effects against LPS-induced tissue damage in mice.

Sex differences in biomarkers of end-organ damage following exertional heat stroke in humans.

Women are participating in military and athletic activities in the heat in increasing numbers, but potential sex differences in sequelae from exertional heat illness remain poorly understood. We tested the hypothesis that women suffering from exertional heat stroke (EHS) would have similar severity of organ damage biomarkers compared with men, as measured in a hospital setting. We studied women and men presenting with EHS to the emergency department at Fort Moore, GA. We measured creatinine (CR), creatine kinase (CK), alanine-transaminase (ALT), aspartate aminotransferase (AST), and estimated glomerular filtration rate (eGFR). Core temperature was also assessed by medical personnel. Biomarker data were obtained for 62 EHS cases (11 women). Men were significantly taller, and heavier, and had larger body mass index (BMI) and body surface area (P < 0.05 for all). The highest recorded body core temperature was not different between groups [women: 41.11°C (40.06, 41.67); men: 41.11°C (40.28, 41.72), P = 0.57]. Women had significantly lower peak CR [women: 1.39 (1.2, 1.48) m·dL-1; men: 1.75 (1.53, 2.16) mg·dL-1, P < 0.01] and peak CK [women: 584 (268, 2,412) U·L-1; men: 2,183 (724, 5,856) U·L-1, P = 0.02]. Peak ALT and AST were not different between groups; during recovery time points, ALT and AST were either similar or lower in women. Women spent approximately half as much time in the hospital following admittance compared with men. Our findings suggest that women may be less susceptible to organ injury resulting from EHS. Further research is necessary to understand the pathophysiology underlying these differences and how biomarkers of end-organ damage severity can differ between women and men following EHS.NEW & NOTEWORTHY We studied otherwise healthy women and men after exertional heat stroke in a military training environment. Peak values for biomarkers of kidney and muscle damage were lower in women compared with men despite similar (highest recorded) body core temperatures. During recovery, organ damage markers were similar or lower in women. These sex differences may indicate differences in the pathophysiology of responses, but more work is needed to clarify specific mechanisms.

Reduced systemic microvascular function in patients with resistant hypertension and microalbuminuria: an observational study.

Resistant hypertension (RH) may be associated with microalbuminuria (MAU), a marker of cardiovascular risk and target organ damage, and both may be related to microvascular damage. Laser speckle contrast imaging (LSCI) is an innovative approach for noninvasively evaluating systemic microvascular endothelial function useful in the context of RH with or without MAU. Microalbuminuria was defined as a urine albumin-to-creatinine ratio between 30 and 300 mg/g. Microvascular reactivity was evaluated using LSCI to perform noninvasive measurements of cutaneous microvascular perfusion changes. Pharmacological (acetylcholine [ACh], or sodium nitroprusside [SNP]) and physiological (postocclusive reactive hyperemia [PORH]) stimuli were used to evaluate vasodilatory responses. Thirty-two patients with RH and a normal urine albumin-to-creatinine ratio (RH group) and 32 patients with RH and microalbuminuria (RH + MAU) were evaluated. Compared with patients without MAU, patients with RH + MAU showed reduced endothelial-dependent systemic microvascular reactivity, as demonstrated by an attenuation of microvascular vasodilation induced by PORH. On the other hand, ACh-induced vasodilation did not differ between groups. The results also revealed reduced endothelial-independent (SNP-induced) microvascular reactivity in hypertensive patients with MAU compared with patients without MAU. In this study, there was evidence of endothelial dysfunction associated with impaired microvascular smooth muscle function in patients with RH + MAU. This may suggest that patients with RH need more intensive therapeutic strategies for the control of blood pressure to avoid further vascular damage and the resulting consequences.The study was registered at ClinicalTrials.gov ( https://register.clinicaltrials.gov ) under protocol # NCT05464849, initial release 12/07/2022.

Extracellular volume fraction of liver and pancreas using spectral CT in hypertensive patients: A comparative study

BACKGROUND: Besides the direct impact on the cardiovascular system, hypertension is closely associated with organ damage in the kidneys, liver, and pancreas. Chronic liver and pancreatic damage in hypertensive patients may be detectable via imaging. OBJECTIVE: To explore the correlation between hypertension-related indicators and extracellular volume fraction (ECV) of liver and pancreas measured by iodine maps, and to evaluate corresponding clinical value in chronic damage of liver and pancreas in hypertensive patients. METHODS: A prospective study from June to September 2023 included abdominal patients who underwent contrast-enhanced spectral CT. Normal and various grades of hypertensive blood pressure groups were compared. Upper abdominal iodine maps were constructed, and liver and pancreatic ECVs calculated. Kruskal-Wallis and Spearman analyses evaluated ECV differences and correlations with hypertension indicators. RESULTS: In 300 patients, hypertensive groups showed significantly higher liver and pancreatic ECV than the normotensive group, with ECV rising alongside hypertension severity. ECVliver displayed a stronger correlation with hypertension stages compared to ECVpancreas. Regression analysis identified hypertension severity as an independent predictor for increased ECV. CONCLUSIONS: ECVliver and ECVpancreas positively correlates with hypertension indicators and serves as a potential clinical marker for chronic organ damage due to hypertension, with ECVliver being more strongly associated than ECVpancreas.

Abstract P108: Correlations of attended and unattended office blood pressure measurements with Left Ventricular Mass in untreated hypertensives.

Introduction: Unattended (UA) office blood pressure (BP) measurements have been proposed as better substitutes for attended (AT) BP readings for the diagnosis and monitoring of patients with hypertension (HTN). A superior correlation of UA over AT BP measurements with Left Ventricular Hypertrophy (LVH), an early marker of hypertensive organ damage has not been conclusively demonstrated. We hypothesized that in a group with untreated HTN, UA BP would correlate more strongly with left ventricular hypertrophy than AT BP. Methods: Newly diagnosed untreated patients with HTN presenting newly to an outpatient clinic in Nigeria were consented as part of a larger study. Three sets of AT and UA seated BP readings were carried out using a validated device followed by same-day echocardiographic assessment of their Left Ventricular Mass Indexed to Body surface area (LVMI). Pearson’s coefficient (r) was determined and a 2-tailed significance was defined by a two-tailed P value (P) less than 0.05. Coefficients were compared using Fisher r to z transformation. Results: A total of 49 participants (female=25) were recruited with a mean age of 46.2 +/- 9 years. The mean of the AT BP in the cohort (mAT) was 157.1 +/- 13.5mmHg, while the mean of the UA BP was 151.9 +/- 15.7 with no significant difference in both (P=0.085). The mean LVMI of the cohort was 102.3 +/- 28.7 mg/m2. Both the mAT BP (r= 0.304, P= 0.034) and the mUA BP (r=0.354, P=0.013) positively correlated with LVMI, with no significant difference in the strength of both correlations with r to z transformation (z=0.27, P=0.394 ). Conclusion: In a small cohort of newly diagnosed Nigerian hypertensives, both attended and unattended systolic office blood pressure readings correlated positively with left ventricular mass indexed to body surface area, with no significant difference in the strength of their correlation. Having failed to demonstrate a superior correlation of unattended blood pressure readings with LVH, our findings support the continued use of attended office blood pressure readings for clinical monitoring in busy time-constrained office settings where unattended office blood pressure monitoring may not be feasible. Larger studies are however required to confirm these findings.

O107 A LONGITUDINAL STUDY ON THE IMPACT OF CHILDHOOD ELEVATED BLOOD PRESSURE ON TARGET ORGAN HEALTH IN ADOLESCENCE: THE EXAMIN YOUTH SA STUDY

Background and objective: Primary hypertension in children is becoming a global threat for the growing economic burden of hypertension management in adulthood and sustainable healthcare. We determined the associations of adolescent blood pressure (BP) with target organ damage markers (carotid intima-media thickness (CIMT) and left ventricular mass index (ilVM)) over a four year period, stratified by childhood BP status at baseline. Methods: We included 421 Black and 307 White South African adolescents (mean age: 11.04 years) with complete follow-up data for BP, CIMT and iLVM. Standard anthropometric measures and basic demographic information were collected. Results: Children were stratified by baseline BP status, i.e., normotensive; n=454 (57.5% Black and 57.7% female) and elevated BP; n=274 (58.4% Black and 52.2% female), with comparable proportions of ethnicity (p=0.81) and sex (p=0.15). Systolic BP (by 6mmHg; p&lt;0.001), diastolic BP (by 3mmHg; p&lt;0.001) and perfusion pressure (by 4mmHg; p&lt;0.001) as well as sex-specific body mass index for age z-scores (BAZ; p&lt;0.001) were all higher in the elevated BP compared to normotensive group. Groups were comparable for age (p=0.78), CIMT (p=0.28) and iLVM (p=0.64). In partial regression analysis (adjusting for ethnicity, sex, follow-up age and BAZ), systolic BP correlated positively with CIMT (r=0.125; p=0.041) and iLVM (r=0.184; p=0.002) in the elevated BP group only. Backward multiple adjusted linear regression analysis (adjustment for perfusion pressure at baseline, age, sex, ethnicity and BAZ) showed adverse associations of systolic BP with CIMT (β=0.126; p=0.046) and iLVM (β=0.199; p=0.001), and diastolic BP with iLVM (β=0.130; p=0.002), only in children with elevated BP at baseline. Conclusion: Elevated BP in early childhood contributes to the long-term impact on target organ health during adolescence independent of sex and ethnicity, while the association of BP with iLVM seems to be moderated by excess adiposity.

Cognitive Outcomes in Young Adults with Primary Arterial Hypertension: The Role of Cardiovascular Risk Factors and Hypertension-Mediated Organ Damage.

Background and Objectives: We aimed to explore the association between cognitive performance and markers of hypertension-mediated organ damage (HMOD) in young adults with hypertension. Materials and Methods: A group of adults aged 16 to 45 years with primary arterial hypertension completed a battery of paper-pencil as well as computer-based neuropsychological tests across all major cognitive domains. They also underwent office and ambulatory 24 h blood pressure, intima-media thickness measurements, heart ultrasound, and laboratory analysis of their lipid profile, blood uric acid concentration, and urine albumin-creatinine ratio. Associations between cognitive test results and markers of HMOD were explored through correlation analysis and age-, sex-, and body mass index-adjusted linear regression modeling. Results: Seventy-six individuals (62, 81.6% male) aged 36.5 years (interquartile range 18.4 to 42.0 years) were enrolled. After adjusting for age, sex, and body mass index in linear regression models, worse categorical fluency was associated with higher left ventricular mass (βst = -0.264, p = 0.043) and worse performance in a task of sustained attention-with higher left ventricular mass index (βst = -0. 304, p = 0.016). Worse phonemic fluency was related to higher pulse pressure (βst = -0.241, p = 0.049) in the respective model. Better strategy use in the task of spatial working memory was linked to higher daytime mean diastolic blood pressure (βst = -0.343 p = 0.017). Conclusions: Performance among young adults with hypertension across selected cognitive domains was inversely associated with pulse pressure, markers of left ventricular damage, and directly associated with daytime diastolic blood pressure. Our study suggests that the previously reported relationship between cognitive and cardiovascular markers in hypertension exists earlier than in middle or late adulthood.

Ambulatory Blood Pressure Phenotypes, Arterial Stiffness, and Cardiac Remodeling.

Evidence on the association of arterial stiffness and left ventricular (LV) concentric remodelling/LVH assessed by echocardiography, with abnormal blood pressure (BP) phenotypes, defined by office and ambulatory BP monitoring (ABPM) in the community is scanty. Thus, we investigated this issue in the participants to the Pressioni Monitorate E Loro Associazioni (PAMELA) study. The present study included 491 participants who attended the second and third survey of the PAMELA study performed after 10 and 25 years from the initial evaluation. Data collection included medical history, anthropometric parameters, blood examinations, office, ABPM, echocardiographic and Cardio-Ankle Vascular Index (CAVI) measurements. In the whole study sample (age 66+10 years, 50% males), the prevalence rates of sustained normotension (NT), white coat hypertension (WCH), masked hypertension (MH), sustained hypertension (SH) and non-dipping (ND) were 31.2, 10.0, 24.2, 34.6, and 35.8% and respectively. The likelihood of having SH, the BP phenotype carrying the greatest CV risk, was four times higher (OR= 4.31, CI:2.39-7.76, p<0.0001) in participants with increased CAVI and LV remodelling/LVH compared to their counterparts without organ damage. This association showed an incremental value in discriminating SH compared to both isolated markers of organ damage (OR=1.92,p=0.03 for increased CAVI and OR= 2.02, p=0.02 for LV remodelling/LVH). The presence of isolated but also combined organ damage was unrelated to ND. Our study provides new evidence of the incremental value of looking for both vascular and cardiac target organ damage to optimize the identification and clinical management of SH in the general population.

Effect of early endothelial function improvement on subclinical target organ damage in hypertensives

Endothelial dysfunction is acknowledged as a marker for subclinical target organ damage (STOD) in hypertension, though its therapeutic potential has not yet been clarified. This study assessed whether early endothelial function improvement (EEFI) reduced STOD in patients with essential hypertension (EH). We conducted a retrospective cohort analysis of 456 EH patients initially free from STOD. Endothelial function was assessed using brachial artery flow-mediated dilation (FMD), with values ≤ 7.1% indicating dysfunction. Patients were initially categorized by endothelial status (dysfunction: n = 180, normal: n = 276), and further divided into improved or unimproved groups based on changes within three months post-enrollment. During a median follow-up of 25 months, 177 patients developed STOD. The incidence of STOD was significantly higher in patients with initial dysfunction compared to those with normal function. Kaplan–Meier analysis indicated that the improved group had a lower cumulative incidence of STOD compared to the unimproved group (p < 0.05). Multivariable Cox regression confirmed EEFI as an independent protective factor against STOD in EH patients (p < 0.05), regardless of their baseline endothelial status, especially in those under 65 years old, non-smokers, and with low-density lipoprotein cholesterol levels ≤ 3.4 mmol/L. In conclusion, EEFI significantly reduces STOD incidence in EH patients, particularly in specific subgroups, emphasizing the need for early intervention in endothelial function to prevent STOD.

Cell Free DNA in SLE Patients: A Possible Marker of Disease Activity and Organ Damage

Abstract Background Systemic lupus erythematous (SLE) is a prototypic autoimmune disease with a complex pathogenesis involving multiple genetic and environmental factors. Cell death has been regarded as an important event in lupus pathogenesis as it leads to release of antigens as nucleic acids for immune complex formation. DNA-antibody complex in the circulation are one of the hallmarks of SLE that leads to detrimental effects causing manifestations of SLE. Fluctuation in circulating DNA level might be one of the driving factors behind flare-ups of SLE. Objectives This study aims to measure the circulating cell free DNA (cf-DNA) in patients with SLE as a potential marker for disease activity and organ damage. Methods This case control study included 100 participants categorized into 75 SLE patients as patient group (Group I), further divided to 39 SLE patients without therapy (group Ia), 36 SLE patients with therapy (Group Ib) and 25 age and sex matched healthy subjects as a control group (Group II). All participants were subjected to full history taking, thorough rheumatological examination and lab assessment of complete blood count (CBC), ESR, CRP, C3, C4 levels, ANA titer, anti-ds-DNA concentration by ELIZA and measurement of plasma cf-DNA levels by real time PCR. Cf- DNA concentration is expressed as concentration (ng/ml). Results SLE patients (Group Ia and Ib) showed significant increase in (plasma cf-DNA,CRP, ESR, ANA, anti-ds-DNA), significant decrease in (C3 and C4, hemoglobin, total leucocytic count and platelet count). Plasma cf-DNA (ng/ml) was significantly lower in group Ib compared to group Ia. There was significant positive correlation between plasma cf-DNA (ng/ml) and levels of ANA and anti-ds-DNA in all SLE patients and with SLEDAI-2k score in all patients. Conclusion Plasma level of cf-DNA is significantly increased in SLE patients especially before starting therapy these data may suggest it to be a possible marker of treatment follow up. Further studies on a larger patient population are still needed to confirm these results.

The Relationship between updated Systemic Coronary Risk Estimation (SCORE 2) and markers of subclinical atherosclerosis and target organ damage in asymptomatic population with metabolic syndrome

The Relationship between updated Systemic Coronary Risk Estimation (SCORE 2) and markers of subclinical atherosclerosis and target organ damage in asymptomatic population with metabolic syndrome

Lack of Association of Vascular Risk Factors with HIV-Associated Neurocognitive Disorders in cART-Treated Adults Aged ≥ 50 Years in Tanzania.

HIV-associated neurocognitive disorders (HAND) are highly prevalent in those ageing with HIV. High-income country data suggest that vascular risk factors (VRFs) may be stronger predictors of HAND than HIV-disease severity, but data from sub-Saharan Africa are lacking. We evaluated relationships of VRFs, vascular end-organ damage and HAND in individuals aged ≥ 50 in Tanzania. c-ART-treated individuals were assessed for HAND using consensus criteria. The prevalence of VRFs and end organ damage markers were measured. The independent associations of VRFs, end organ damage and HAND were examined using multivariable logistic regression. Data were available for 153 individuals (median age 56, 67.3% female). HAND was highly prevalent (66.7%, 25.5% symptomatic) despite well-managed HIV (70.5% virally suppressed). Vascular risk factors included hypertension (34%), obesity (10.5%), hypercholesterolemia (33.3%), diabetes (5.3%) and current smoking (4.6%). End organ damage prevalence ranged from 1.3% (prior myocardial infarction) to 12.5% (left ventricular hypertrophy). Measured VRFs and end organ damage were not independently associated with HAND. The only significant association was lower diastolic BP (p 0.030, OR 0.969 (0.943-0.997). Our results suggest that vascular risk factors are not major drivers of HAND in this setting. Further studies should explore alternative aetiologies such as chronic inflammation.

Hypertension and arterial wall stiffness in clinical practice: literature review

Arterial stiffness, as a marker of subclinical target organ damage in patients with hypertension (HTN), is an important and independent predictor of mortality and cardiovascular morbidity. The review examines factors contributing to increased vascular wall stiffness with a focus on smoking, pathogenesis of increased arterial stiffness with aging, and the effect of arterial stiffness on increased systolic and pulse pressure. Particular attention is paid to the effect of pulse pressure on the risk of cardiovascular events, primarily on the incidence of stroke and cognitive impairment. Thiazide-like diuretics and calcium antagonists have the greatest evidence base in HTN treatment in the elderly due to their ability to reduce systolic and pulse pressure, reduce arterial stiffness and have a positive effect on prognosis. The use of amlodipine/indapamide retard combination promotes more effective treatment of elderly patients with HTN.

Gut Microbiota Improves Prognostic Prediction in Critically Ill COVID-19 Patients Alongside Immunological and Hematological Indicators.

The gut microbiota undergoes substantial changes in COVID-19 patients; yet, the utility of these alterations as prognostic biomarkers at the time of hospital admission, and its correlation with immunological and hematological parameters, remains unclear. The objective of this study is to investigate the gut microbiota's dynamic change in critically ill patients with COVID-19 and evaluate its predictive capability for clinical outcomes alongside immunological and hematological parameters. In this study, anal swabs were consecutively collected from 192 COVID-19 patients (583 samples) upon hospital admission for metagenome sequencing. Simultaneously, blood samples were obtained to measure the concentrations of 27 cytokines and chemokines, along with hematological and biochemical indicators. Our findings indicate a significant correlation between the composition and dynamics of gut microbiota with disease severity and mortality in COVID-19 patients. Recovered patients exhibited a higher abundance of Veillonella and denser interactions among gut commensal bacteria compared to deceased patients. Furthermore, the abundance of gut commensal bacteria exhibited a negative correlation with the concentration of proinflammatory cytokines and organ damage markers. The gut microbiota upon admission showed moderate prognostic prediction ability with an AUC of 0.78, which was less effective compared to predictions based on immunological and hematological parameters (AUC 0.80 and 0.88, respectively). Noteworthy, the integration of these three datasets yielded a higher predictive accuracy (AUC 0.93). Our findings suggest the gut microbiota as an informative biomarker for COVID-19 prognosis, augmenting existing immune and hematological indicators.

Developing a Clinically Relevant Hemorrhagic Shock Model in Rats.

Over the recent decades, the development of animal models allowed us to better understand various pathologies and identify new treatments. Hemorrhagic shock, i.e., organ failure due to rapid loss of a large volume of blood, is associated with a highly complex pathophysiology involving several pathways. Numerous existing animal models of hemorrhagic shock strive to replicate what happens in humans, but these models have limits in terms of clinical relevance, reproducibility, or standardization. The aim of this study was to refine these models to develop a new model of hemorrhagic shock. Briefly, hemorrhagic shock was induced in male Wistar Han rats (11-13 weeks old) by a controlled exsanguination responsible for a drop in the mean arterial pressure. The next phase of 75 min was to maintain a low mean arterial blood pressure, between 32 mmHg and 38 mmHg, to trigger the pathophysiological pathways of hemorrhagic shock. The final phase of the protocol mimicked patient care with an administration of intravenous fluids, Ringer Lactate solution, to elevate the blood pressure. Lactate and behavioral scores were assessed 16 h after the protocol started, while hemodynamics parameters and plasmatic markers were evaluated 24 h after injury. Twenty-four hours post-hemorrhagic shock induction, the mean arterial and diastolic blood pressure were decreased in the hemorrhagic shock group (p< 0.05). Heart rate and systolic blood pressure remained unchanged. All organ damage markers were increased with the hemorrhagic shock (p < 0.05). The lactatemia and behavioral scores were increased compared to the sham group (p < 0.05). In conclusion, we demonstrated that the protocol described here is a relevant model of hemorrhagic shock that can be used in subsequent studies, particularly to evaluate the therapeutic potential of new molecules.

O95: The role of the complement system in mediating ischaemic cholangiopathy in DCD liver transplantation

Abstract Background The discrepancy between available organs and the number of patients on the waiting list have led to an increasing number of donor after circulatory death (DCD) liver grafts being used. DCD liver grafts suffer from a higher risk of ischaemic cholangiopathy, the pathophysiology of which is poorly understood. We hypothesized that the complement system mediates damage to the arterial endothelium, thereby affecting the ability of cholangiocytes to regenerate. Methods Livers declined for clinical transplantation were perfused for up to 10 hours with anti-coagulated packed red cells at 37° with or without complement inhibition. Levels of circulating complement components, tissue binding of complement proteins, and organ damage markers were measured. Results 5 DBD and 5 DCD livers were perfused, and 5 further DCD livers being perfused with eculizumab. C3 production was significantly higher in the untreated DCD cohort compared to DBD livers at 10 hours (52.68 mg/ml vs 8.62 mg/ml, p&amp;lt;0.005). C5b-9 deposition on the arterial endothelium of the portal tracts was significantly higher in the untreated DCD cohort compared to the treated DCD livers (mean 0.9 R.U vs 0.4 R.U, p&amp;lt;0.05). There was a non-significant difference in bile production and composition between the treated DCD and untreated DCD cohort. Conclusions There is evidence that the complement system mediates the damage to the arterial endothelium within the portal tracts of the liver. This damage could be ameliorated by complement inhibition. Further work to correlate this findings with clinical outcomes will be required.

Novel drug therapy of acute hepatic failure induced in rats by a combination of tadalafil and Lepidium sativum

BackgroundHepatocyte death and a systemic inflammatory response are the outcome of a complex chain of events mediated by numerous inflammatory cells and chemical mediators. The point of this study was to find out if tadalafil and/or Lepidium sativum (L. sativum) could help people who have been exposed to carbon tetrachloride (CCL4) and are experiencing acute moderate liver failure. This was especially true when the two were used together.Method and materialsTo cause mild liver failure 24 h before sacrifice, a single oral dosage of CCL4 (2.5 mL/kg b.w.) (50% in olive oil) was utilized. Furthermore, immunohistochemical expression of nuclear factor kappa B (NF-κB) as well as histological abnormalities were performed on liver tissue.ResultsThe results showed that tadalafil and/or L. sativum, especially in combination, performed well to cure acute mild liver failure caused by CCL4. This was demonstrated by a decrease in NF-κB expression in the liver tissue and an improvement in organ damage markers observed in the blood and liver tissues. Furthermore, such therapy reduced interleukin1 beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels in the liver tissue. It’s worth noting that the tested combination resulted in greater liver improvement.ConclusionsAccording to the findings, tadalafil and L. sativum, particularly in combination, have the ability to protect the liver from the negative effects of CCL4 exposure. Because of its capacity to improve liver function, restore redox equilibrium, and decrease inflammatory mediators, it is a prospective option for mitigating the negative effects of common environmental pollutants such as CCL4.

Immobilisation efficacy of conducted electrical weapons on captive white-tailed deer

Context Wildlife emergencies (e.g. injured animals) often require capture or humane dispatch of animals to resolve the situation. Conducted electrical weapons (CEWs) have the potential to immobilise white-tailed deer (Odocoileus virginianus) for a short duration to avoid potential risks of extended immobilisation (e.g. chemical immobilisation) and increase safety for managers and the public during humane killing by gunshot. Aims To test rapid immobilisation with minimal long-term physiological consequences of CEW immobilisation of white-tailed deer. Methods We arranged five treatment groups of captive deer, including (1) chemical immobilisation with 5-s CEW exposure (n = 5), (2) chemical immobilisation with 15-s CEW exposure (n = 5), (3) 5-s CEW exposure with no chemical immobilisation (n = 10), (4) 15-s CEW exposure with no chemical immobilisation (n = 10) and (5) a control group with no chemical immobilisation or CEW exposure (n = 10). We conducted treatments 1 and 2 to determine short-term physiological effects of CEWs on deer, related to overall welfare. In treatment groups 1 and 2, we sedated deer to collect blood immediately before CEW exposure, and 2 days and 5 days post-exposure for serum biochemical analysis (to measure physiological markers of organ and tissue damage). We observed deer before, during and after treatments to evaluate potential behavioural changes. Key results All deer showed signs of muscle paralysis immediately after exposure to CEW and regained muscle control immediately after the exposure ended. Serum biochemistry results for treatment group 1 and 2 revealed significant increases in creatine kinase (CK) and aspartate aminotransferase (AST) 2 days post-treatment, before returning to pre-exposure concentrations by day 5-post-exposure, suggesting temporary myopathy. By 15-days post-exposure, deer that were only exposed to the CEW had 27 of 39 (69%) remotely fired probes still attached. No long-term behavioural or physiological changes were observed post-treatment. Conclusions Our findings suggest that for immobilisation of white-tailed deer, short-term exposure to a CEW to is a potential alternative to typical capture techniques and can provide sufficient immobilisation to approach and humanely kill deer by gunshot if necessary in wildlife emergencies. Implications As with all capture techniques, trainings and protocols should be developed to ensure the safety of personnel and animals during CEW exposures.

Degree of organ damage and inflammatory markers in sepsis mice models inducted by various doses of lipopolysaccharides

Background Sepsis is a life-threatening disease, and animal models of sepsis are minimal. This study aims to find the optimal dose of LPS to make a sepsis mouse model by examining the presence of target organ damage. Methods This study used 30 mice divided into four groups. The control group (3 mice) injected 0.5 cc NaCl 0.9% intraperitoneally (i.p.). Group A (9 mice) was injected with lipopolysaccharides (LPS) 0.125 mg/kg B.W. i.p. given on the first and second day, group B (9 mice) was injected with LPS 0.15 mg/kg B.W. i.p. given on the first and second days, and group C (9 mice) was injected by LPS 0.3 mg/kg B.W. single dose i.p. On the third, fourth, and fifth days, the termination of each group of three mice and examination of the NF-κB, tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), alanine aminotransferase (ALT), the expression of NF-κB in the liver and kidneys, and histopathology in the liver and kidneys were conducted. Results NF-κB, C-reactive protein (CRP), alanine aminotransferase (ALT), NF-κB examinations, and tumor necrosis factor-α (TNF-α) in all treatment groups increased when compared with the control. The highest degree of histopathological features of the kidneys and liver and the results of immunohistochemistry examinations on the liver and kidneys were shown in group C. Conclusions The optimal dose of LPS to make a sepsis mouse model was 0.3 mg/kgB.W with the most severe target organ damage dan significant increased of inflammatory markers.