18,765 research outputs found

    Comparison of electrical impedance tomography and spirometry-based measures of airflow in healthy adult horses

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    Electrical impedance tomography (EIT) is a non-invasive diagnostic tool for evaluating lung function. The objective of this study was to compare respiratory flow variables calculated from thoracic EIT measurements with corresponding spirometry variables. Ten healthy research horses were sedated and instrumented with spirometry via facemask and a single-plane EIT electrode belt around the thorax. Horses were exposed to sequentially increasing volumes of apparatus dead space between 1,000 and 8,500 mL, in 5–7 steps, to induce carbon dioxide rebreathing, until clinical hyperpnea or a tidal volume of 150% baseline was reached. A 2-min stabilization period followed by 2 minutes of data collection occurred at each timepoint. Peak inspiratory and expiratory flow, inspiratory and expiratory time, and expiratory nadir flow, defined as the lowest expiratory flow between the deceleration of flow of the first passive phase of expiration and the acceleration of flow of the second active phase of expiration were evaluated with EIT and spirometry. Breathing pattern was assessed based on the total impedance curve. Bland-Altman analysis was used to evaluate the agreement where perfect agreement was indicated by a ratio of EIT:spirometry of 1.0. The mean ratio (bias; expressed as a percentage difference from perfect agreement) and the 95% confidence interval of the bias are reported. There was good agreement between EIT-derived and spirometry-derived peak inspiratory [−15% (−46–32)] and expiratory [10% (−32–20)] flows and inspiratory [−6% (−25–18)] and expiratory [5% (−9–20)] times. Agreement for nadir flows was poor [−22% (−87–369)]. Sedated horses intermittently exhibited Cheyne-Stokes variant respiration, and a breath pattern with incomplete expiration in between breaths (crown-like breaths). Electrical impedance tomography can quantify airflow changes over increasing tidal volumes and changing breathing pattern when compared with spirometry in standing sedated horses

    AAZTA-Like Ligands Bearing Phenolate Arms as Efficient Chelators for 68Ga Labelling in vitro and in vivo

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    : The introduction of a phenolate pendant arm in place of an acetate on AAZTA- and DATA-like ligands resulted in hepta- and hexadentate chelators able to form Ga(III) complexes with thermodynamic stability and kinetic inertness higher than that of other Ga(III) complexes based on the parent 6-amino-6-methylperhydro-1,4-diazepine scaffold. In particular, the heptadentate AAZ3A-endoHB with a phenolate arm on an endocyclic N-atom shows a logKGaL of 27.35 and a remarkable resistance to hydroxide coordination up to basic pH (pH>9). This behaviour allows to also improve the kinetic inertness of the complex showing a dissociation half-life (t1/2 ) at pH 7.4 of 76 h. Although also the hexadentate AAZ2A-exoHB chelator forms a stable (logKGaL =24.69) and inert (t1/2 =33 h at pH 7.4) Ga(III) complex, the 68 Ga labelling showed a better radiochemical yield with AAZ3A-endoHB, especially at room temperature. Thus, a bifunctional chelator of AAZ3A-endoHB was synthesized bearing an isothiocyanate group that was conjugated to the N-terminus of a c(RGD) peptide for integrin receptor targeting. Finally, the conjugate was successfully labelled with 68 Ga isotope, and the resulting radiotracer tested for its stability in human serum and then in vivo for targeting B16-F10 tumours with miniPET imaging

    Preclinical safety and efficacy of a therapeutic antibody that targets SARS-CoV-2 at the sotrovimab face but is escaped by Omicron

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    The recurrent emerging of novel viral variants of concern (VOCs) with evasion of preexisting antibody immunity upholds severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) case numbers and maintains a persistent demand for updated therapies. We selected the patient-derived antibody CV38-142 based on its potency and breadth against the VOCs Alpha, Beta, Gamma, and Delta for preclinical development into a therapeutic. CV38-142 showed in vivo efficacy in a Syrian hamster VOC infection model after post-exposure and therapeutic application and revealed a favorable safety profile in a human protein library screen and tissue cross-reactivity study. Although CV38-142 targets the same viral surface as sotrovimab, which maintains activity against Omicron, CV38-142 did not neutralize the Omicron lineages BA.1 and BA.2. These results highlight the contingencies of developing antibody therapeutics in the context of antigenic drift and reinforce the need to develop broadly neutralizing variant-proof antibodies against SARS-CoV-2

    Association between spinal cord compression ratio in magnetic resonance imaging, initial neurological status, and recovery after ventral slot in 57 dogs with cervical disc extrusion

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    This retrospective, unblinded, single rater study evaluated images obtained from magnetic resonance imaging (MRI) of dogs with cervical intervertebral disc extrusion before being submitted to ventral slot decompression (VSD). Dogs were re-evaluated systematically at 10 and 30 days after VSD. The objectives of this study were to investigate the associations between the following parameters: (1) The maximal spinal cord compression ratio (SCCR) as seen on transverse MRI and pre-surgical neurological status (NS) grade; we hypothesized that dogs with greater SCCR will have worse pre-surgical NS grade at presentation; (2) Pre-surgical NS grade and postoperative recovery; we hypothesized that worse pre-surgical NS grade will be associated with longer postoperative recovery time; (3) SCCR and postoperative recovery; we hypothesized that dogs with higher SCCR will have longer recovery time; (4) Location of extrusion (cranial vs. caudal) and initial NS grade and outcomes; we hypothesized that caudal cervical extrusion will have worse NS grade and longer time to recovery; (5) Longitudinal extension of ventral CSF signal loss on HASTE pulse sequence and NS grade and time to recovery; we hypothesized that dogs with longer HASTE CSF attenuation will have higher NS grade and longer time to recovery. There was no significant association between SCCR and NS grade, suggesting that this relationship in the cervical region is similar to what is observed in the thoracolumbar region, rejecting our first hypothesis. There was a significant difference between ambulatory tetraparesis dogs versus non-ambulatory tetraparesis dogs regarding complete recovery at 10 days: dogs with NS grade 1, 2, or 3 overall recovered faster than dogs with NS grade 4. However, there was no significant difference between these groups regarding complete recovery at 30 days, thereby accepting our second hypothesis at 10 days and rejecting it at 30 days. There was no correlation between SCCR and recovery time, rejecting our third hypothesis. Caudal cervical extrusion did not show higher NS grade or longer recovery time than cranial extrusion, rejecting our fourth hypothesis. CSF attenuation length ratio on HASTE images was not significantly correlated with NS grade but weakly correlate with post-surgical recovery time, partially accepting our fifth hypothesis

    Southern Adventist University Undergraduate Catalog 2022-2023

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    Southern Adventist University\u27s undergraduate catalog for the academic year 2022-2023.https://knowledge.e.southern.edu/undergrad_catalog/1121/thumbnail.jp

    神経調節性失神の病態メカニズム解明と薬物治療への応用

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    【はじめに】神経調節性失神は血管迷走神経性失神、状況失神、頸動脈洞症候群からなり、様々な誘因によって交感神経抑制と副交感神経緊張が惹起され血圧低下や徐脈を呈する病態である。獣医臨床分野においても、犬で排便・排尿・咳嗽・嚥下によって自律神経反射が誘発された失神が報告されている。この反応は刺激受容器から求心性神経を介して孤束核へと入力し、延髄腹外側野を経由して迷走神経と交感神経の遠心路に投射すると考えられているが、その病態生理の詳細に関しては未だ不明な部分が多い。そこで本研究では延髄に多く分布しているneurokinin-1受容体に着目した。Neurokinin-1受容体は延髄を中心として中枢神経系に広く発現し、種々の行動、内分泌および自律神経機能に関与している。内因性リガンドであるsubstance-Pとともに侵害受容、情動 (不安や抑うつ) および嘔吐などへ影響することが示されている。これらの生理学的な背景を受け、neurokinin-1受容体の拮抗薬を用いることで、自律神経が関与した反射を抑制できる可能性があると考えた。本研究の第1章では犬の神経調節性失神における臨床例を報告し、その治療方針および治療における課題に関して考察した。第2章ではラットを用い、結腸直腸拡張によって反射性の血圧降下を誘発させた実験モデルを作成した。選択的nuerokinin-1受容体拮抗薬であるホスアプレピタントを投与した群と、生理食塩水を投与した群での循環動態の変化を観察した。続いてラットの脳組織を使用し、c-Fos法を用いて延髄最後野、延髄孤束核および尾側延髄腹外側野における神経活動評価を実施した。これらの実験によって得られた結果から、自律神経反射におけるneurokinin-1受容体の関与と、その拮抗薬の薬物治療への応用の可能性について考察した。第1章:犬の神経調節性失神の症例報告【背景】神経調節性失神は獣医臨床分野で排便・排尿・咳嗽・嚥下に関連した状況失神としてしばしば遭遇する疾患である。神経調節性失神の治療は誘因の排除や、発生した不整脈に対する薬物療法が中心となるが、その治療選択肢は限られている。この度、各種検査を実施し神経調節性失神と臨床診断した僧帽弁閉鎖不全症の犬の症例を経験したため、その病態・治療に関する考察を行った。【症例】症例は咳嗽および興奮時に失神を繰り返しており、僧帽弁閉鎖不全症の診断を受けていた。失神の原因精査のため麻布大学附属動物病院に紹介来院した。【経過および考察】心臓超音波検査および胸部レントゲン検査を実施し、僧帽弁粘液腫様変性性疾患: ACVIM Stage B1と診断された。この重症度では明確な臨床徴候がみられないのが一般的であり、器質的心疾患は失神の主因ではないと思われた。失神発作は咳嗽および興奮と関連して発生していることから神経調節性失神の可能性が高いと考えられたため、ホルター心電図検査を実施した。ホルター心電図の装着期間中、咳嗽時に洞停止が出現した。臨床徴候および検査所見から神経調節性失神と臨床診断した。本症例では失神の誘因となっている咳嗽に対し、内科的治療を開始した。加えて、興奮・運動時にも洞停止を呈している可能性があったため、過度な興奮や運動を控えるよう生活指導を行った。神経調節性失神には上記のような治療選択がとられるものの、根治は困難であり、しばしば対症療法的な方針をとることになる。求心性の迷走神経刺激に対しては誘因の排除を主軸とし、遠心性経路すなわち徐脈や血圧降下に対してはそれぞれの事象に対する薬物療法を行うことが主な治療となる。しかしながら反射回路である中枢神経に着目した治療は未だ確立されていない。そこで、本研究では神経調節性失神発現時の中枢神経における伝達経路を解明し、新たな薬物療法を提案することを本研究の目的とした。第2章:反射性血圧降下誘発ラットにおける循環動態の変化と延髄におけるneurokinin-1受容体の関与【背景】神経調節性失神の症例に対する主な治療アプローチは、失神の因子となる病態のコントロールを行い、失神の誘因となる生活イベントを避け、時に不整脈に対する薬物治療を行うこととなる。しかしながら、自律神経反射経路そのものに着目した薬物治療は未だ確立されていない。そこで神経調節性失神発現時の中枢神経における反射経路に着目し、求心性迷走神経と延髄を介した伝達経路を薬理学的にブロックすることで病態のコントロールが可能なのではないかと着想した。第2章では自律神経反射を誘発したラットを用いてneurokinin-1受容体拮抗薬の効果を検証した。続いて、自律神経反射経路に関与するとされる延髄最後野、孤束核、尾側延髄腹外側野の神経活動をc-Fos法で評価することによって、neurokinin-1受容体と自律神経反射経路の関連を検証した。【材料および方法】結腸直腸拡張による循環動体の変化:雄のWisterラットを用い、ウレタン麻酔下で実験を行った。ラットは結腸直腸拡張群 (CRD群) とホスアプレピタント投与群 (CRD+NK1A群) に分類した。麻酔導入後、肛門から6 cmの深さまで直径2 cmの拡張バルーンを挿入した。結腸直腸拡張手技の開始40分前に、CRD群では生理食塩水10 ml/kgを、CRD+NK1A群ではホスアプレピタント 30 mg/kgを腹腔内投与した。結腸直腸拡張手技は10秒間で拡張圧を目標値まで上昇させ、40秒間目標値を維持し、10秒かけて0 mmHgに下降させた。この操作を合計3回、目標拡張圧40、60、80 mmHgの順で実施し、拡張間のインターバルはそれぞれ5分間確保した。延髄における神経活動評価:結腸直腸拡張手技の終了後に灌流固定を行い、脳を摘出した。ビブラトームを使用して厚さ50 μmの組織切片を作成し、ABC法およびDAB法を用いて延髄最後野、延髄孤束核および尾側延髄腹外側野におけるc-Fos陽性細胞の定量的な比較を行った。加えて、組織学的な陰性コントロールとして、結腸直腸拡張を行わない非刺激群 (Control群) のラットを用意した。【結果および考察】結腸直腸拡張によって、いずれの拡張圧においても拡張前から有意な血圧降下がみられた。今回の実験モデルでは結腸直腸拡張による求心性迷走神経刺激によって交感神経活性の低下が惹起されたものと考えられ、神経調節性失神の病態を部分的に再現していると思われた。CRD群とCRD+NK1A群の両群間の比較では、80 mmHg拡張時においてCRD群と比較してCRD+NK1A群で有意に血圧の変化幅が小さかった。なお心拍数は両群で有意差はみられなかった。この結果から、選択的neurokinin-1受容体拮抗薬の全身投与は結腸直腸拡張によって誘発された血圧降下を抑制する可能性が示された。神経活動評価では、延髄最後野のc-Fos陽性細胞数は群間で有意な差はみられなかった。孤束核ではControl群と比較してCRD群でc-Fos陽性細胞が有意に多くみられたが、CRD群とCRD+NK1A群で有意差はみられなかった。一方、尾側延髄腹外側野ではControl群と比較してCRD群およびCRD+NK1A群でc-Fos陽性細胞が有意に多くみられ、CRD群とCRD+NK1A群の比較ではCRD+NK1A群のほうがc-Fos陽性細胞の数が有意に少なかった。【総括】Neurokinin-1受容体拮抗薬は結腸直腸拡張刺激によって誘発された反射を抑制する可能性が示唆された。反射性血圧降下における延髄の神経活動は、延髄への求心性入力領域である延髄最後野や孤束核では群間で有意差がみられなかったのに対し、抑制性の投射を担う尾側延髄腹外側野では有意差がみられた。このことからneurokinin-1受容体は延髄内の神経伝達経路でその役割を担っていると考えられた。本研究の結果は、臨床現場で治療選択肢の限られる神経調節性失神に対し、neurokinin-1受容体拮抗薬が新たな治療選択肢としての可能性を有することを示した。今回は排便失神の部分的再現方法として結腸直腸拡張を選択したが、今後は異なる自律神経反射モデル動物においても選択的neurokinin-1受容体拮抗薬の有用性について検討する必要がある。本研究成果は、獣医臨床分野のみならず人医療における神経調節性失神の治療確立に貢献すると考えられる。[Introduction]Neurally mediated syncope refers to a condition in which the balance between sympathetic and parasympathetic tone is disrupted by various triggers, leading to hypotension and bradycardia. In veterinary medicine, syncope has been observed in dogs due to triggers such as defecation, urination, coughing, and swallowing. However, the underlying mechanism remains unclear. This study focuses on neurokinin-1 receptors, which are widely expressed in the central nervous system and play a role in various functions, including pain, emotion, and emesis. The study hypothesis is that an antagonist of the neurokinin-1 receptor may be used to inhibit autonomic-mediated reflexes. The study consists of three chapters: Chapter 1 reports a clinical case of neurally mediated syncope in a dog, Chapter 2 describes an experimental model of reflex-induced hypotension in rats, and evaluated neural activity in the medulla oblongata of the rats using the c-Fos method. The results suggest a potential role for neurokinin-1 receptor antagonists in treating autonomic reflexes.Chapter 1: Case Report of neurally mediated syncope in a Dog [Background]Neurally mediated syncope is a frequently encountered condition in veterinary medicine as situational syncope related to defecation, urination, coughing, and swallowing. This report describes a case of a dog with typical neurally mediated syncope.[Case]The patient had repeatedly been fainting during coughing and was being diagnosed of mitral regurgitation. She was referred to Azabu University Veterinary Hospital to investigate the cause of her syncope.[Progress and Discussion]After performing echocardiography and chest radiography, a mitral valve myxomatous degenerative disease diagnosis was ACVIM Stage B1. The cardiac disease did not appear to be the primary cause of syncope, as no clear clinical signs are common in this disease severity. The history of. syncope were associated with coughing, a neurally mediated syncope was considered likely, and a Holter electrocardiogram was performed. During Holter ECG, sinus arrest appeared just before the onset of syncope. Based on clinical signs and Holter ECG findings, a clinical diagnosis of neurally mediated syncope was made. The patient was followed up with medical therapy for a cough. Although treatment options are available for neurally mediated syncope as mentioned above, it is often difficult to cure completely, and symptomatic treatment is often necessary. Therefore, I decided to delineate a mechanism of reflex hypotension by focusing on the reflex circuit in the central nervous system and to find out a new drug candidate of the central mechanism.Chapter 2: Involvement of the Neurokinin-1 Receptor and Circulatory Changes in Rats with Reflex Hypotension[Background]The primary therapeutic approach for cases of neurally mediated syncope, as described in Chapter 1, is to control the pathophysiological conditions that contribute to syncope and then avoid life events that trigger syncope, sometimes with pharmacological treatment that increases the basal heart rate. However, no medical treatment have yet been developed focusing on the autonomic reflex pathway. Therefore, this research focused on the reflex pathways in the central nervous system during neurally mediated syncope and hypothesized that pharmacological blockade of the afferent vagal and medulla oblongata pathways would allow control of the condition. [Materials and Methods][Colorectal Distension]Male Wister rats were used for the experiments under urethane anesthesia. Rats were classified into a colorectal distension group (CRD group) and a fosaprepitant group (CRD+NK1A group). After induction of anesthesia, a distension balloon with a diameter of 2 cm was inserted to a depth of 6 cm from the anus. In Group CRD, 10 ml/kg of saline solution was administered intraperitoneally before colorectal distension; in Group CRD+NK1A, 30 mg/kg of fosaprepitant was administered as well. Colorectal distension was performed for 10 s to increase the balloon pressure to the target value, maintained at the target value for 40 s, and then lowered to 0 mmHg over 10 s. This procedure has performed three times at target distension pressures of 40, 60, and 80 mmHg, in that order, with an interval of 5 min between each stimulus.[c-Fos immunoreactive cells]The tissue sections 50 µm thick were prepared using a vibratome, and a quantitative comparison of c-Fos positive cells in the area postrema, the nucleus of the solitary tract, and the caudal ventrolateral medulla was performed using ABC and DAB methods. Rats in the non-stimulated group (Control group), in which no colorectal distension technique was performed, were also prepared as histologically negative controls.[Results and Discussion]A significant decrease in blood pressure was observed with colorectal distension compared to pre-stimulation at all balloon pressures. A slight increase in heart rate was observed only during 80 mmHg distension. Comparison between the CRD and CRD+NK1A groups showed that at 80 mmHg distension, blood pressure was significantly lower in the CRD+NK1A group than in the CRD group, suggesting that the afferent vagal stimulation induced a decrease in sympathetic nerve activity. The CRD+NK1A group showed a significantly smaller change in blood pressure at 80 mmHg distension than the CRD group. There was no significant difference in heart rate between the two groups. These results suggest that the administration of a selective neurokinin-1 receptor antagonist may attenuate the hypotension induced by colorectal distension.Chapter 2 demonstrated that neurokinin-1 receptor antagonists might attenuate the hypotension induced by colorectal distension. The c-Fos method was used to evaluate the neuronal activity in the medulla oblongata, the nucleus of the solitary tract, and the ventral lateral area of the caudal medulla oblongata, which are thought to be involved in autonomic reflex pathways, to investigate the association between neurokinin-1 receptors and vagal reflexes by evaluating neuronal activity in the medulla oblongata, the area postrema, the nucleus of the solitary tract, and the caudal ventrolateral medulla by the c-Fos method.The number of c-Fos-positive cells in the area postrema did not differ significantly between groups. In the nucleus of the solitary tract, more c-Fos-positive cells were found in the CRD group than in the Control group, but there was no difference between the CRD and CRD+NK1A groups. On the other hand, in the caudal ventrolateral medulla, the number of c-Fos-positive cells was lower in the CRD+NK1A group than in the CRD group.[Conclusion]The present study suggests that neurokinin-1 receptor antagonists may inhibit reflexes evoked by colorectal distension. Neuronal activity in the present study did not differ between groups in the area postrema and the nucleus of the solitary tract, which are afferent input areas to the medulla oblongata. In contrast, it did differ in the caudal ventrolateral medulla, which is responsible for the inhibitory projection. This suggests that neurokinin-1 receptors play a role in neurotransmitter pathways within the medulla oblongata. Based on the pharmacological properties of neurokinin-1 receptor antagonists, they may suppress blood pressure variability in autonomic reflexes induced by stimulation of receptors other than colorectal distension. It is necessary to investigate the usefulness of selective neurokinin-1 receptor antagonists in different types of stimuli of autonomic reflexes in the future. The results of this study will contribute to the establishment of the treatment of neurally mediated syncope in the veterinary medicine and human medicine.博士(獣医学)麻布大

    Gastroesophageal Foreign Bodies in Dogs - Endoscopy and Surgical Removal

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    Background: Gastroesophageal foreign bodies (GFD) are commonly diagnosed in dogs and are considered an endoscopic emergency that, although not resulting in serious clinical sequelae or mortality, can compromise the health and well-being of the patient. The use of the digestive endoscopy for the diagnosis and treatment of GFD can be a valuable and viable alternative. There are cases of GFD in dogs for which the indicated treatment is surgery, which can be performed using minimally invasive or conventional techniques, associated or not with flexible endoscopy. The objective of this work is to describe 16 cases of GFD removal in dogs demonstrating the efficiency of upper digestive endoscopy. Cases: Of the 16 GFD cases, 63% (10/16) were male and 37% (6/16) female. Most aged under 1 year (63%), puppies (5/16) and juveniles (5/16). The patient with the lowest body weight was a miniature pinscher weighing 0.8 kg (Case 14) and the heaviest was an American Pit Bull Terrier weighing 28 kg (Case 11), the mean body weight of patients diagnosed with GFD was 10.2 ± 6.7 kg. Small and medium breeds were more affected, 44.7% (7/16) and 44.7% (7/16), respectively, and large breeds (Golden Retrievier and Bull Terrier), from cases 1 and 4, the least affected, 12.6% (2/16) of the cases. The 16 patients underwent a 12 h food fast and a 4 h water fast, as gastrointestinal emptying in these cases of GFD can be influenced by these foreign bodies. All underwent general inhalation anesthesia with monitoring of physiological parameters (temperature, heart rate, respiratory rate, oxygen saturation and blood pressure) before, during and after EGD, being positioned in left lateral decubitus. The 16 canine patients with suspected GFD underwent EGD for diagnostic confirmation and removal of foreign bodies. Five esophageal FB were diagnosed, 31% (5/16), and 11 gastric FB, 69% (11/16). The most frequently diagnosed foreign bodies were bone and tissue, 37.5% (6/16) and 31% (5/16). Other foreign bodies were materials such as plastics, metals, rubber, foam and stone. Of the 16 cases of GFD, EGD efficiently treated 88% (14/16) without the need for hospitalization, with only supportive treatment for the remission of complications caused by the presence of foreign bodies in the gastroesophageal tract. The main complications related to the presence of GFD were esophagitis in 25% (4/16) of cases, gastritis in 38% (6/16) and both alterations in 13% (2/16). Discussion: In this work, we can observe that more than a third of the clinical cases of treated dogs were diagnosed with GFD, demonstrating that these cases are common in the veterinary clinic. Most of these animals were males less than 1 year old. The improvement of learning in this category can lead these animals to exacerbated oral exploration of new objects. Most FBs were found in the stomach because they were of adequate size, consistency and shape for their passage through the esophagus, whereas esophageal FBs were all bone fragments of rigid consistency with diameters and sizes larger than the esophageal lumen. The interval between the ingestion of the object and the veterinary care can be decisive for the removal of the FB in the esophagus or stomach. Most gastric FBs removed were fabrics and plastics, flexible objects that can pass through the esophageal lumen more easily. Removal of GFD by endoscopy was performed with a high success rate, with only 2 cases being resolved by esophagostomy and gastrotomy. Flexible endoscopy proved to be an efficient technique for removing treated GFD, which can help remove FB during esophagotomy and be associated with rigid endoscopy. Patients recovered quickly and without complications, but it is important to emphasize that inadequate maneuvers and conducts can determine other outcomes. The use of endoscopy for GFD removal needs to be more popularized, as it can ensure better results for dogs treated with GFD. Keywords: digestive tract, endoscopic extraction, flexible endoscopy, ingested object, rigid endoscopy

    Moringa oleifera seeds attenuate benzene-induced alterations in lipid peroxidation and antioxidant enzymes in liver and kidney tissues of Wistar rats

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    Benzene is a notorious toxicant that is responsible for a host of diseases including leukemia. Its concentration in the environment is increasing day-by-day due to excessive automobile use, accelerated industrial activities and cigarette smoke. The awareness on the harmful effects of benzene on health is limited and no antidote has been reported yet. In this study, an attempt has been made to find out a suitable remedy to overcome benzene toxicity in a living organism from a natural source with the seeds of the plant Moringa oleifera (MO). Thirty six Wistar rats were considered for the study and divided into six groups (n=6). While group I remained as control with normal animals, those in groups II – VI received benzene by oral route (800 mg/kg body weight) for 28 consecutive days. On day 29, the benzene-treated animals in groups III – VI received respectively the standard drug ascorbic acid (AA, 25 mg/kg body weight) and MO (50, 100 and 200 mg/kg body weight) for the following 7 days. Group II rats that received only benzene served as negative control without any treatment. On day 36, all the animals were sacrificed and vital organs liver and kidney were removed for studying lipid peroxidation (LPO) and antioxidant markers [Superoxide dismutase (SOD), Total reduced glutathione (TRG), Glutathione peroxidase (GPx) and Catalase (CAT)] in addition to histopathological changes in the tissues. The results of the study revealed that significant changes occurred in the above parameters due to benzene dosing to animals were reverted to near normal values on MO administration in the liver and kidney tissues as compared to untreated animals, suggesting MO’s pro-active role in attenuating benzene toxicity

    Direct activation of the fibroblast growth factor-21 pathway in overweight and obese cats

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    IntroductionFeline obesity is common, afflicting ~25–40% of domestic cats. Obese cats are predisposed to many metabolic dyscrasias, such as insulin resistance, altered blood lipids, and feline hepatic lipidosis. Fibroblast Growth Factor-21 (FGF21) is an endocrine hormone that mediates the fat-liver axis, and in humans and animals, FGF21 can ameliorate insulin resistance, non-alcoholic fatty liver disease, and obesity. Activation of the FGF21 pathway may have therapeutic benefits for obese cats.MethodsIn this preliminary cross-sectional study, ad libitum fed, purpose-bred, male-neutered, 6-year-old, obese and overweight cats were administered either 10 mg/kg/day of an FGF21 mimetic (FGF21; n = 4) or saline (control; n = 3) for 14 days. Body weight, food, and water intake were quantified daily during and 2 weeks following treatment. Changes in metabolic and liver parameters, intrahepatic triglyceride content, liver elasticity, and gut microbiota were evaluated.ResultsTreatment with FGF21 resulted in significant weight loss (~5.93%) compared to control and a trend toward decreased intrahepatic triglyceride content. Cats treated with FGF21 had decreased serum alkaline phosphatase. No significant changes were noted in liver elasticity, serum, liver, or metabolic parameters, or gut microbiome composition.DiscussionIn obese and overweight cats, activation of the FGF21 pathway can safely induce weight loss with trends to improve liver lipid content. This exploratory study is the first to evaluate the FGF21 pathway in cats. Manipulation of the FGF21 pathway has promising potential as a therapeutic for feline obesity. Further studies are needed to see if FGF21-pathway manipulation can be therapeutic for feline hepatic lipidosis

    Epidural Analgesia for Pain Management in the Intensive Care Unit

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    The pain of patients admitted into the ICU remains poorly reported and managed. It has been reported that about half of patients admitted to both medical and surgical ICU experienced significant pain during their stay in the unit. Most of these patients tend to develop psycho-traumatic experiences both while in the unit and after discharge. This chapter thus highlights the drawback of poor pain management of critically ill patients and the role of epidural analgesia in contributing to better pain control in the ICU
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