Animal Observational Studies Research Articles

The role of iron supplementation in reducing all-cause mortality of heart failure patients with iron deficiency: a systematic review and meta-analysis

Abstract Background Many heart failure patients also suffer from anemia suggesting potential therapeutic targets. However, the role of iron supplementation in patients with heart failure with iron deficiency in reducing all-cause mortality remains unclear. Purpose We aim to compare the risk of all-cause mortality in iron deficient heart failure patients who were given iron therapy versus placebo. Methods We systematically searched for RCTs comparing Fe supplementation with placebo in heart failure patients with iron deficiency from PubMed, Scopus, Science Direct, and ProQuest up to March 2021. The inclusion criteria was Randomized Controlled Trial Study with outcome of all-cause mortality. The exclusion criteria were observational studies, animal studies, and studies without English language. Odds ratio (OR) was calculated with 95% confidence interval (CI), while heterogeneity was assessed using the I2 statistics. The primary outcome was all-cause mortality. Data from eligible studies were pooled for effect estimates. Statistical analysis was performed using Review Manager software. Results From literature search, 7 RCTs were obtained. The total patients used for pooled analysis were 1192 patients receiving iron therapy and 973 patients receiving placebo. Pooled analysis using a random-effect model showed that iron therapy use was not associated with better all-cause mortality in heart failure patients with iron deficiency (OR: 0.91; 95% CI: 0.68–1.23; p: 0.56; I2: 0%). The funnel plot was asymmetric, suggesting presence of publication bias. Conclusion No benefit of Fe supplementation in reducing all-cause mortality of heart failure patients with iron deficiency. Funding Acknowledgement Type of funding sources: None. Pooled analysis for all-cause mortality

Ultrasound-guided Percutaneous Dilatational Tracheotomy: A fast and safe technique for airway management

Purpose: To describe a modified technique for percutaneous dilational tracheotomy (PDT) offering possible significant advantages over currently used procedures.
 Methods: An observational animal study using ultrasound for PDT was performed. After pre-incisional ultrasonic examination, and with continuing ultrasound guidance, the trachea was punctured with an 18-gauge introducer needle and a tracheal tube was inserted using the Seldinger technique and a Ciaglia single dilator. Setting: University Hospital animal laboratory center. Subjects: 11 pietrain pigs (weight 26–36 kg).
 Results: Successful tracheotomy was accomplished in all 11 pigs. The mean duration of the procedure was 20 seconds from skin penetration to guide wire placement. In one pig, the dorsal wall of the trachea was punctured.
 Conclusion: This novel procedure is a simple and effective technique for PDT tube placement.

An Atmospheric Plasma Jet Induces Expression of Wound Healing Genes in Progressive Burn Wounds in a Comb Burn Rat Model: A Pilot Study.

Burn-related injuries are devastating injuries with a high mortality rate that affect people of all ages worldwide. We assessed the effectiveness of plasma jet treatment in altering the expression of genes involved in wound healing in a prospective longitudinal observational animal study. Six male Sprague-Dawley rats weighing 350 g were used, and burn wounds were made by applying a preheated brass comb (100°C) to the back of the rats, resulting in four full-thickness burn wounds separated by three interspaces. A total of 18 burn wounds were induced on three rats. One side of the burn, on each rat received plasma treatment (plasma group), while the other side did not (control group). The interspaces were subjected to the plasma jet for 2 minutes per day until 7 days post-wounding. Plasma treatment significantly decreased the expression of proinflammatory cytokines. Furthermore, an increase in the expression of anti-inflammatory cytokines was observed in the plasma group. We showed that plasma jet treatment could improve burn wound healing by altering the expression of genes involved in the development of wound healing.

The potential role of incretin-based therapies for polycystic ovary syndrome: a narrative review of the current evidence.

Introduction:Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age. Metabolic consequences associated with PCOS include, but are not limited to, insulin resistance (IR), type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). This narrative review aims to provide a comprehensive overview of the potential therapeutic roles of the incretin-based therapies in the management of PCOS.Methods:We performed a systematic search of databases including PubMed, MEDLINE and EMBASE up to 1 October 2020. We developed a search string of medical subject headings (MeSH) including the terms PCOS, incretin mimetics, glucagon-like peptide-1 (GLP-1), glucagon-like peptide-1 receptor antagonists (GLP-1 RAs), liraglutide, exenatide, semaglutide, dipeptidyl peptidase-4 (DPP-4) inhibitors, combined with IR, testosterone and sex hormone-binding globulin (SHBG).Results:We identified 854 relevant articles and, after the initial screening, eight interventional animal studies, one observational animal study, 14 interventional human studies, two case–control studies and one systematic review were included. These studies showed the potential significant roles of GLP-1 RAs and DPP-4 inhibitors in the management of PCOS, with significant improvements in the metabolic parameters, including substantial weight reduction and improved insulin sensitivity. These agents also improved the hormonal parameters through decreased free androgen and increased SHBG. Moreover, they improved menstrual regularity, increased fertility with enhanced ovulation and pregnancy in obese women with PCOS.Conclusion:GLP-1 RAs and DPP-4 inhibitors have a promising therapeutic role in PCOS; however, larger clinical trials are needed to establish the role of incretin-based therapies in the management of PCOS.

Methodology for experimental and observational animal studies in cow-calf contact systems.

In this Research Reflection we describe a common standpoint on suitable methodology for controlled and observational studies in cow-calf contact systems in dairy production. Different methods to assess behaviour, health and production in cow-calf contact systems are outlined. Knowledge and experience from researchers working in this field supplement scientific literature whenever relevant. Specific methods including study design, early behaviour of cow and calf, social behaviour relevant to cow-calf contact systems, human-animal relationships and aspects related to management (milking, weaning and separation, health) are reviewed, and recommendations formed. We expect that this paper can contribute to a better understanding of the complexity of cow-calf contact systems and help to advance research in this area of dairy production.

S100B protein and neuron-specific enolase as predictors of postoperative cognitive dysfunction in aged dogs: a case-control study

ObjectivePostoperative cognitive dysfunction (POCD) may be related to brain injury. S100B protein and neuron-specific enolase (NSE) have been investigated as potential biochemical markers of neural cell injury in animals and humans. This study aimed to investigate the association between POCD, brain injury and serum concentrations of S100B and NSE after periodontal surgery in aged dogs. Study designProspective observational animal study. AnimalsA total of 24 male and female dogs undergoing periodontal surgery. MethodsDogs were separated into two groups based on age: control group, 10 dogs ≤ 8 years and aged group, 14 dogs > 8 years. Cognitive function was measured preoperatively and on the seventh postoperative day using the Canine Cognitive Dysfunction Rating scale and the Age-Related Cognitive and Affective Disorders scale. S100B protein and NSE serum concentrations were measured before and immediately after the surgery. ResultsPOCD was not observed after surgery in the present study. Serum concentrations of S100B and NSE were increased postoperatively in the control group but not in the aged group (p = 0.04 and 0.03, respectively). Preoperative S100B serum concentrations were significantly higher in the aged group (p = 0.01). ConclusionsThere was no association between POCD and high concentrations of S100B and NSE in dogs. However, increased postoperative serum concentrations of S100B and NSE were found in the control group after surgery, an effect that may indicate neural damage. Clinical relevanceThe results suggest that anesthesia and oral surgery are associated with higher postoperative serum concentrations of S100B and NSE in dogs ≤ 8 years old, which may indicate neural damage. Serum concentrations of S100B were elevated in aged dogs before anesthesia, a finding that might be related to chronic preoperative brain damage.

Correction: Cisplatin-Induced Non-Oliguric Acute Kidney Injury in a Pediatric Experimental Animal Model in Piglets.

[This corrects the article DOI: 10.1371/journal.pone.0149013.].

Renal Tubular Cell Mitochondrial Dysfunction Occurs Despite Preserved Renal Oxygen Delivery in Experimental Septic Acute Kidney Injury.

To explain the paradigm of significant renal functional impairment despite preserved hemodynamics and histology in sepsis-induced acute kidney injury. Prospective observational animal study. University research laboratory. Male Wistar rats. Using a fluid-resuscitated sublethal rat model of fecal peritonitis, changes in renal function were characterized in relation to global and renal hemodynamics, and histology at 6 and 24 hours (n = 6-10). Sham-operated animals were used as comparison (n = 8). Tubular cell mitochondrial function was assessed using multiphoton confocal imaging of live kidney slices incubated in septic serum. By 24 hours, serum creatinine was significantly elevated with a concurrent decrease in renal lactate clearance in septic animals compared with sham-operated and 6-hour septic animals. Renal uncoupling protein-2 was elevated in septic animals at 24 hours although tubular cell injury was minimal and mitochondrial ultrastructure in renal proximal tubular cells preserved. There was no significant change in global or renal hemodynamics and oxygen delivery/consumption between sham-operated and septic animals at both 6- and 24-hour timepoints. In the live kidney slice model, mitochondrial dysfunction was seen in proximal tubular epithelial cells incubated with septic serum with increased production of reactive oxygen species, and decreases in nicotinamide adenine dinucleotide and mitochondrial membrane potential. These effects were prevented by coincubation with the reactive oxygen species scavenger, 4-hydroxy-2,2,6,6-tetramethyl-piperidin-1-oxyl. Renal dysfunction in sepsis occurs independently of hemodynamic instability or structural damage. Mitochondrial dysfunction mediated by circulating mediators that induce local oxidative stress may represent an important pathophysiologic mechanism.

Histological effects of fibrin glue and synthetic tissue glues on the spinal cord: are they safe to use?

Introduction: Fibrin glues such as Tisseel® have been established in neurosurgery for over thirty years. They are recommended for extradural use but have intradural applications. Brachial plexus reimplantation after trauma requires intradural fibrin glue because reimplanted nerves cannot be sutured to the spinal cord. Recently synthetic glues have become popular in spinal surgery but there is limited information about their safety. Our study compared the histological effects of Tisseel®, Adherus® and BioGlue® on spinal cord using our rat brachial plexus repair model.Materials & methods: Randomised observational animal study. Forty-one Sprague-Dawley rats divided in to control (n = 9), Tisseel® (n = 8), BioGlue® (n = 10) and Adherus® (n = 14) groups. Under general anaesthesia a posterior midline cervical incision was made and hemi-laminectomies performed at C7 and T1. Dura was opened and T1 dorsal root transected and repositioned on the spinal cord. Two drops of Tisseel®, BioGlue®, Adherus® or no glue (control) were applied over the cut nerve and cord. At days 7, 14 and 28 rats were euthanized, processed and sections stained with Haematoxylin & Eosin and evaluated blind by a neuropathologist.Results: Control and Tisseel® groups showed only mild focal inflammation in the cord. Adherus® and Bioglue® groups showed evidence of spinal cord inflammation and degeneration. All BioGlue® and Adherus® rats had evidence of distortion of the cord from the glue mass at all time points. Two BioGlue®-treated and one Adherus®-treated rat developed a hemiparesis. One BioGlue® rat developed hind limb paralysis. One BioGlue® rat failed to wake up at the end of the procedure. There were no complications in control and Tisseel® groups.Conclusion: Tisseel® caused a similar inflammatory response to control and may be used on spinal cord. BioGlue® and Adherus® should be applied thinly for a watertight dural closure but intradural use and contact with spinal tissue must be avoided.

Observational research rigour alone does not justify causal inference.

Differing opinions exist on whether associations obtained in observational studies can be reliable indicators of a causal effect if the observational study is sufficiently well controlled and executed. To test this, we conducted two animal observational studies that were rigorously controlled and executed beyond what is achieved in studies of humans. In study 1, we randomized 332 genetically identical C57BL/6J mice into three diet groups with differing food energy allotments and recorded individual self-selected daily energy intake and lifespan. In study 2, 60 male mice (CD1) were paired and divided into two groups for a 2-week feeding regimen. We evaluated the association between weight gain and food consumption. Within each pair, one animal was randomly assigned to an S group in which the animals had free access to food. The second paired animal (R group) was provided exactly the same diet that their S partner ate the day before. In study 1, across all three groups, we found a significant negative effect of energy intake on lifespan. However, we found a positive association between food intake and lifespan among the ad libitum feeding group: 29·99 (95% CI: 8·2-51·7) days per daily kcal. In study 2, we found a significant (P = 0·003) group (randomized vs. self-selected)-by-food consumption interaction effect on weight gain. At least in nutrition research, associations derived from observational studies may not be reliable indicators of causal effects, even with the most rigorous study designs achievable.

A review on colistin nephrotoxicity.

Colistin is an antibiotic that was introduced many years ago and was withdrawn because of its nephrotoxicity. Nowadays, reemergence of this antibiotic for multi-drug resistant Gram-negative infections, and a new high dosing regimen recommendation increases concern about its nephrotoxicity. This review attempts to give a view on colistin nephrotoxicity, its prevalence especially in high doses, the mechanism of injury, risk factors, and prevention of this kidney injury. The data collection was done in PubMed, Scopus and Cochrane databases. The keywords for search terms were "colistin", "nephrotoxicity", "toxicity", "renal failure", "high dose", and "risk factor". Randomized clinical trials and prospective or retrospective observational animal and human studies were included. In all, 60 articles have been reviewed. Colistin is a nephrotoxic antibiotic; a worldwide increase in nosocomial infections has led to an increase in its usage. Nephrotoxicity is the concerning adverse effect of this drug. The mechanism of nephrotoxicity is via an increase in tubular epithelial cell membrane permeability, which results in cation, anion and water influx leading to cell swelling and cell lysis. There are also some oxidative and inflammatory pathways that seem to be involved in colistin nephrotoxicity. Risk factors of colistin nephrotoxicity can be categorized as dose and duration of colistin therapy, co-administration of other nephrotoxic drugs, and patient-related factors such as age, sex, hypoalbuminemia, hyperbilirubinemia, underlying disease and severity of patient illness.

EFFECT OF DRUGS;

ABSTRACT... Objective: The aim of this study was to determine head-dipping exploratory test parameter as a measure of strongmodulating effect on brain and behavior. Design: It was an observational animal study. Setting: University of Karachi. Period: Jan 2004 toJuly 2006. Material & methods: In this present study, drugs used reserpine, nux- vomica; anacardium and chlorpromazine were widerange of pharmacological actions. We evaluate the effectiveness of these drugs as agents with modulating effect on brain and behavioraccessed by head dipping parameter. In this study, 25 mice were included belonging to both sexes. The study animals were divided intofive groups of five animals each. Four groups were given drugs and one group was kept as control. Mice (20-35g) of either sex were usedin this study. One group was kept as control for drugs. Mice were kept under room temperature. Tap-water was allowed ad-Libitum.30minutes after giving drugs, animals were observed for 10 minutes with two minutes of interval. Tablet crushed in 10ml of water, 1cc wasgiven. Screening method used was head dipping. Results: Strychnos Nux-Vomica when used in a dose of 0.07mg has strong action oncholinergic system, CNS activity and frequent head dipping (39.8±28.8) was observed. Rauwolfia serpentine is an active alkaloidparticularly present in reserpine (62.2±43.4) no significant head dipping effect was observed. Anacardium (37.2±28.6) &Chlorpromazine (39.4±32.4), show decrease effects. Keeping in view, the medicinal importance of these herbs, our present study wasdesigned to screen these drugs for CNS activity on albino mice.

Prevention of vancomycin induced nephrotoxicity: a review of preclinical data

Several strategies have been proposed for the prevention of vancomycin-induced nephrotoxicity. Here, we review available evidence supporting the respective strategies. Data were collected by searching the Scopus, PubMed, and Medline databases and the Cochrane database of systematic reviews. The key words used as search terms were "vancomycin," "nephrotoxicity", "renal failure," "renal damage," "nephroprotective," "renoprotective", and "prevention." Prospective or retrospective observational animal studies that evaluated the effects of a modality for the prevention of vancomycin-induced nephrotoxicity was included. Animal studies show beneficial effects of various antioxidants, such as erdosteine, vitamin E, vitamin C, N-acetylcysteine, caffeic acid phenethyl ester, and erythropoietin, in the prevention of vancomycin-induced nephrotoxicity. However, before these agents can be used in clinical practice, their potential benefits must be confirmed in future randomized controlled human studies.

Correlations between hemodynamic, oxygenation and tissue perfusion parameters during asphyxial cardiac arrest and resuscitation in a pediatric animal model

Aim To analyze the correlations between hemodynamic, oxygenation and tissue perfusion values in an infant animal model of asphyctic cardiac arrest (ACA). Methods A prospective observational animal study was performed in seventy one, two month-old piglets. CA was induced by removal of mechanical ventilation and was followed by advanced life support after at least 10 min. Correlations between hemodynamic [heart rate (HR), mean arterial pressure (MAP), cardiac index (CI), stroke volume index (SVI) and intrathoracic blood index (ITBI) measured by PiCCO method], blood gas values (arterial and central venous saturation), and tissue perfusion values [intramucosal gastric pH (pHi), and tissue oxygenation (cerebral and renal saturation)] were analyzed during asphyxia, resuscitation and after return of spontaneous circulation (ROSC). Results Among global hemodynamic parameters, the only moderate significant correlation observed was between CI and ITBI ( r = .551). Among tissue oxygenation/perfusion values, a moderate to good significant correlation ( r = .460–.763) between arterial oxygen saturation, central venous, renal and cerebral oxygen saturation was observed. Lactic acid, potassium (K) and pHi were correlated ( r = .561–.639), but no correlation was found between them and tissue oxygenation parameters. Global hemodynamic parameters (CI, HR, MAP) did not correlate with renal and cerebral saturations and tissue perfusion parameters. Conclusions During ACA and after ROSC global hemodynamic parameters do not correlate with oxygenation and tissue perfusion values. Additional studies which assess the potential usefulness of tissue oxygenation/perfusion parameters during cardiac arrest and ROSC are needed.

Influence of Tidal Volume on Pulse Pressure Variations in Hypovolemic Ventilated Pigs with Acute Respiratory Distress-like Syndrome

Sensitivity and specificity of respiratory change in pulse pressure (DeltaPP) to predict preload dependency has been questioned at small tidal volumes (VT) in critically ill patients suffering from acute respiratory distress syndrome (ARDS). We studied DeltaPP in pigs with ARDS-like syndrome during reversible hemorrhagic shock. Prospective, observational animal study in a Laboratory Investigation Unit. Sixteen deeply sedated mechanically ventilated pigs were successively ventilated with VT of 10 ml/kg at a respiratory rate of 15 breaths/min (RR15) and VT of 6 ml/kg at RR15 and RR25. ARDS-like syndrome was produced by lung lavage in eight pigs (ARDS group). Severe hemorrhagic shock was induced by removal of 40% of total blood volume followed by restoration. After bleeding, in the control group ventilated with a VT of 10 ml/kg, DeltaPP increased from 8.5 (95% confidence interval [CI], 7.1 to 9.9%) to 18.5% (CI, 15.3 to 21.7%; P<0.05). In the ARDS group, this index increased similarly, from 7.1% (95% CI, 5.3 to 9.0%) to 20.1% (CI, 15.3 to 24.9%; P<0.05). In control lungs, reduction in VT from 10 to 6 ml/kg reduced the DeltaPP reaction by 40%, although it remained a statistically valid indicator of hypovolemia regardless of the RR value. In contrast, in the ARDS group, DeltaPP was an unreliable hypovolemia marker at low VT ventilation, regardless of the RR value (p=not statistically significant). The present study suggests that DeltaPP is a reliable indicator of severe hypovolemia in pigs with healthy lungs regardless of VT or RR. In contrast, in pigs with ARDS-like syndrome ventilated with small VT, DeltaPP is not a good indicator of severe hemorrhage. However, in this setting, indexing DeltaPP to respiratory changes in transpulmonary pressure allows this marker to significantly indicate the occurrence of hypovolemia.

Influence of ventilatory settings on exhaled nitric oxide during high frequency oscillatory ventilation

Nitric oxide (NO), which is produced in the lower airways, diffuses from cells into the air space and can be measured in exhaled air. The influence of high frequency oscillatory ventilation on the production of exhaled NO (eNO) has not been thoroughly studied. The objectives of this study are to establish an animal model for evaluation of lower airway NO and to evaluate settings in terms of frequency, mean airway pressure (MAP), amplitude pressure (amplitude), and inspiratory time ratio (t(I)/t(E)) during high frequency oscillatory ventilation on the production of eNO. An observational animal study was performed on 12 female New Zealand White rabbits, which were anesthetized, tracheotomized and ventilated using a SensorMedics 3100A HFOV ventilator (SM3100A). The concentration of NO in exhaled gas was measured by chemiluminescence continuously from the nose and the side hole of the adaptor of endotracheal tube. The individual effects of the respiratory settings were evaluated. The results were analyzed by paired t-test or by the generalized estimating equation method. We found that the lower airway was the main source of the eNO, that amplitude, MAP, and t(I)/t(E) were positively correlated with the level of eNO and that frequency was negatively correlated with the level of eNO. These findings fit the stretch theory for the production of endogenous NO. Monitoring of eNO during HFOV may provide insights into lung mechanics and ventilation efficiency and be used in the future as a guide during clinical practice.

Balloon-Facilitated Percutaneous Dilational Tracheostomy Tube Placement: Preliminary Report of a Novel Technique

To describe a novel technique for percutaneous tracheotomy (PT) that could be an alternative to current dilational techniques.An observational animal study of PT was performed using the Seldinger guide wire technique with a tracheostomy tube preloaded onto a dilational balloon catheter. A small skin incision was done with an 11-blade scalpel, but no blunt subcutaneous tissue dissection was performed.Animal laboratory in a university hospital.Seven adult pigs (approximate weight, 16 to 21 kg).Successful tracheostomy was accomplished in all seven pigs without apparent complication. Vital signs and oximetry results remained unchanged throughout the procedure. The mean duration of the procedure was 5.5 min from tracheal puncture to ventilation.This novel procedure is a simple and effective means of PT tube placement without subcutaneous tissue dissection and could potentially have decreased complications when compared to the standard methods of PT currently employed in humans. Human studies are pending.

Evolution of the Stone Heart After Prolonged Cardiac Arrest

We hypothesized that progressive impairment in diastolic function during cardiopulmonary resuscitation (CPR) precedes evolution of the "stone heart" after failure of CPR. We therefore measured sequential changes in left ventricular (LV) volumes and free-wall thickness of the heart during CPR in an experimental model. Prospective, observational animal study. Medical research laboratory in an university-affiliated research and educational institute. Domestic pigs. Ventricular fibrillation (VF) was induced in 40 anesthetized male domestic pigs weighing between 38 kg and 43 kg. After 4 min, 7 min, or 10 min of untreated VF, electrical defibrillation was attempted. Failing to reverse VF in each instance, precordial compression at a rate of 80/min was begun coincident with mechanical ventilation. Coronary perfusion pressures (CPPs) were computed from the differences in time-coincident diastolic aortic and right atrial pressures. Left ventricular (LV) systolic and diastolic ventricular volumes and thickness of the LV free wall were estimated with transesophageal echocardiography. The stroke volumes (SVs) were computed from the differences in decompression diastolic and compression systolic volumes. Free-wall thickness was measured on the hearts at autopsy. Significantly greater CPPs were generated with the 4 min of untreated cardiac arrest. Progressive reductions in LV diastolic and SV and increases in LV free-wall thickness were documented with increasing duration of untreated VF. A stone heart was confirmed at autopsy in each animal that failed resuscitative efforts. Correlations with indicator dilution method and physical measurements at autopsy corresponded closely with the echocardiographic measurements. Progressive impairment in diastolic function terminates in a stone heart after prolonged intervals of cardiac arrest.