The role of parasympathetic mechanisms in the infarct-limiting effect of SGLT2 inhibitor ertugliflozin

Introduction: Based on data that outcome in patients with acute myocardial infarction is predicted by final infarct size (IS), reducing IS is of paramount importance. Recent experimental studies have demonstrated a strong infarct-sparing effect of SGLT2 inhibitors – a class of drugs which have proved to be safe and beneficial in patients with heart failure. Repurposing SGLT2 inhibitors for the benefit of patients presenting with acute myocardial infarction should be preceded by investigation of the underlying mechanisms of this infarct limitation. Experimental and clinical data indicate a potential role for autonomic modulation in these mechanisms, specifically sympatho-inhibition. The aim of this study was to investigate the role of the parasympathetic mechanism in the infarct-limiting effect of SGLT2 inhibition. Methods: Fortyeight Sprague Dawley male rats were fed with a standard diet containing either the SGLT2 inhibitor ertugliflozin or vehicle, for 5-7 days. Myocardial ischaemia/reperfusion injury was initiated by a 40-min occlusion of the left anterior descending coronary artery followed by a 2hr period of reperfusion under isoflurane anaesthesia. Bilateral cervical vagotomy was performed 10min prior to myocardial ischaemia. Alternatively, muscarinic receptors were blocked systemically with the non-selective blocker atropine sulphate (2 mg/kg bolus, then 1 mg/kg/h) or the M3-selective blocker 4-DAMP (2 mg/kg bolus). Results: Pre-treatment with ertugliflozin reduced IS in comparison with the vehicle-treated controls (p<0.001). Bilateral vagotomy, atropine sulphate and 4-DAMP all abolished this infarct-limiting effect (IS 35±10%, 44±8%, and 35±4% respectively; P<0.01 vs. Ertu for vagotomy, P<0.001 vs. Ertu for both atropine sulphate and 4-DAMP). Conclusion: These results suggest that the Infarct-limiting effect of the SGLT2 inhibitor ertugliflozin, may be mediated via activation of the vagus nerve and M3-cholinoreceptors.

Evaluation of Clinico-physiological Effects of Ketamine Alone and in Combination with Dexmedetomidine or Butorphanol in Atropinized Dogs

Background: Ketamine is rarely used alone because of its association with poor muscle relaxation, tachycardia, catalepsy or muscle rigidity and therefore commonly used in combination with alpha 2 agonist or opioid to minimize the untoward effects. The aim of the present anaesthetic study was to evaluate the clinico-physiological effects of ketamine alone and in combination with dexmedetomidine or butorphanol for inducing adequate anaesthesia in dogs. Methods: The present anaesthetic study was conducted on 18 (eighteen) healthy dogs of either sex and randomly divided into three groups (K, DK and BK) with six animals in each group. Atropine sulphate @ 0.04 mg/ kg was administered intramuscularly 15 minutes prior to anaesthetic study to all the animals. In group K, ketamine HCl alone was administered @ 5 mg/kg by slow i/v and kept as control. In group DK and BK, after administration of atropine sulphate 15 minutes later dexmedetomidine @ 10 µg/kg i/m and butorphanol @ 0.2 mg/kg i/m were administered respectively. Ten minutes later ketamine HCl was administered @ 5 mg/kg slowly intravenously in both group DK and BK to induce surgical stage of general anaesthesia. The following clinical parameters were recorded viz., onset of sedation, onset of anaesthesia, degree of analgesia, extent of muscle relaxation, duration of anaesthesia and complete recovery. The physiological parameters (rectal temperature, heart rate and respiratory rate) were recorded before anaesthetic study at 0 min. and at 10 minutes after preanaesthetic administration and then at 10, 20, 40, 60, 90, 120 and 180 minutes after ketamine anaesthesia. All the data were analyzed using SPSS v 15.0 statistics software program and presented as mean±Standard Error. Result: The onset of sedation was quicker in group DK followed by group K and BK. Duration of anaesthesia and complete recovery in group DK was significantly (p less than 0.01) longer than in group K and BK. The degree of analgesia was excellent in group DK and good in group K and BK. The extent of muscle relaxation was excellent in group DK, good in group BK and was poor in group K. The physiological parameters showed transient changes which compensated and remained within normal range during the observation period. The above anaesthetic study suggests that ketamine in combination with dexmedetomidine or butorphanol can be safely used for inducing adequate anaesthesia in dogs. However, dexmedetomidine-ketamine can be used safely for longer duration of surgical procedures in dogs.

Evaluation of Phytochemical and Anti-diarrheal Activity of Methanol Stembark Extract of Combretum hypopilinum Diels (Combretaceae)

Introduction: The plant Combretum hypopilinum has many medicinal uses in Africa. Infusion of fresh or dry leaves are commonly taken as cholagogic, diuretic, and purgative and also to treat gastrointestinal disorders, including diarrhoea, dysentery, and stomach achesObjective: To carry out phytochemical and antidiarrheal studies on the methanol stembark extract of C. hypopilinum.Methods: The C. hypopilinum stembark (1kg) were extracted with methanol using cold maceration method for 9 days. The solvent was removed by rotary evaporator and the extract was partitioned with n-hexane, chloroform and ethyl acetate to give the n-hexane, chloroform, and ethyl acetate fractions respectively. The extract was subjected to preliminary phytochemical screening, acute toxicity study and antidiarrheal activity using animal models.Result: The following metabolites: carbohydrates, alkaloids, phenol, steroids, terpenes, saponins, flavonoids and tannins were revealed when the phytochemical screening of the plant extract was carried out. The oral median lethal dose (LD50) of crude extract in mice and rats was estimated to be above 5000 mg/kg. The antidiarrheal activity carried out at dose 150, 300 and 600 mg/bw i.p. using castor oil induced diarrheal, gastric-transit time and anti-enteropooling tests in mice and rats. The extract significantly (P<0.05) inhibited diarrheal in mice and rats with highest protection/ inhibition of 93.1% and 87.9% at doses of 600 and 300 mg/kg (dose dependently) which compared with atropine sulphate (86.2%) respectively, in the castor-oil induced diarrheal test in mice. The extract also significantly (P<0.05) inhibited diarrheal in charcoal meal test with the highest % protection of 24.38% at dose 600 mg/kg and compared with loperamide (28.80%). The anti-enteropooling test in rats showed 68% inhibition of diarrheal as compared to atropine sulphate with 78% inhibition.Conclusion: The results indicated that the methanol stembark extract of Combretum hypopilinum possesses significant dose dependant antidiarrheal activity (p<0.05) in all the antidiarrheal tests. Thus, the traditional use of the plant for the treatment of diarrheal is highly justified in this study.

Management of canine urolithiasis by cystotomy in a two-year old Lhasa Apso bitch

Canine urolithiasis is a common urinary tract disease requiring a rapid definitive diagnosis for immediate surgical and/or non-surgical therapy. The calculi may be microscopic or macroscopic, and when detected, the condition should be treated, either surgically or conservatively. This paper presents a surgical management of urolithiasis in a two-year old Lhasa apso bitch. The dog was haematuric for two weeks and had been on ceftriaxone and diclofenac for the period. Urolithiasis was confirmed following ultrasonography. The dog was pre-medicated with 0.02 mg/kg atropine sulphate and 2 mg/kg xylazine, while anaesthesia was induced and maintained with 10 mg/kg of 5% ketamine. Following aseptic patient preparation, the peritoneal cavity was accessed via a caudal ventral midline incision. The bladder was incised and the uroliths were evacuated via a cystotomy incision. Retrograde flushing of the urethra was performed to propel uroliths into the bladder for removal. The urinary bladder was closed with polyglycolic acid in Lambert suture pattern. The peritoneum and muscles were sutured using catgut in simple continuous suture. The skin was closed with silk using horizontal mattress suture pattern. The dog recovered uneventfully from the surgery and the wound healed after two weeks, at which time the skin suture was removed Keywords: Bladder, calculi, cystotomy, urolith, urolithiasis.

Management of Accidentally Injected Ivermectin Overdose Inflicted Toxicity in German Shepherd Dog

An owner complaint about adverse reaction half an hour after accidental injection of ivermectin to a dog. The dog showed hyperthermia, bradycardia, dyspnoea, hypersalivation and frothy discharge, dilated pupil and ataxia. The dog was symptomatically treated with normal saline, dexamethasone, tribivet-M and atropine sulphate. Adverse symptoms were abolished after two hours. Instant reporting by the owner and prompt treatment in the present study helps to avoid further deterioration in the dog's condition and made possible fast recovery.

Antidiarrhoeal activity of fractions of aqueous extract of Mangifera indica L. leaves in castor oil-induced diarrhoeal female Wistar rats

Background: The aqueous extract of Mangifera indica leaves (AEMIL) has been substantiated for its antidiarrhoeal activity without information on the antidiarrhoeal-rich solvent fraction.Aim: This study evaluated the antidiarrhoeal activity of solvent–solvent fractions from M. indica leaves in female Wistar rats.Setting: This is laboratory animal-based phytopharmacological investigation conducted at the University of Ilorin.Methods: Aqueous extract of M. indica leaves was successfully fractionated to give ethyl acetate fraction (EAF), n-butanol fraction (NBF) and aqueous residual fraction (ARF). The fractions at 25, 50 and 100 mg/kg body weight (bw) were screened for antidiarrhoeal activity. The antidiarrhoeal index (ADI) was also computed.Results: Ethyl acetate fraction, NBF and ARF significantly (p 0.05) extended the onset of diarrhoea, reduced fecal parameters (number, weight and water content of feaces and number of diarrhoeal feaces), masses and volumes of intestinal fluid, distance covered by charcoal meal, peristaltic index and its inhibition, with ARF exhibiting the most pronounced effects. The ADI at 25 and 100 mg/kg bw (equivalent doses of 14.09 and 56.3 mg/kg bw, respectively) of ARF which were 55.19 and 49.87, respectively were similar to 48.50 produced by loperamide/atropine sulphate. The ADI of 32.36 and 10.18 for 100 mg/kg bw each (equivalent of 26.41 and 17.24 mg/kg bw) of EAF and NBF respectively, were lower than that of loperamide/atropine sulphate (48.50).Conclusion: Of all the fractions, the 25 mg/kg bw of ARF produced the most profound antidiarrhoeal activity via anti-motility and anti-secretory mechanisms.

Clinical signs associated with a case of iatrogenic poisoning by a turpentine-based commercial product in a 3-day-old foal

The aim of this study is to report a case of iatrogenic poisoning by a turpentine-based commercial product in a 3-day-old foal and the successful treatment of this condition. A 3-day-old male foal presented with acute cardio-respiratory collapse, anaphylactic shock, severe respiratory distress, dyspnea and pulmonary edema. The animal’s history included previous administration of a commercial veterinary product (UNITIPAN). Clinical examination revealed: temperature: (39.9 °C), pulse: 135 bpm, respiration: 51 bpm, mucous membranes: moist and congested, capillary refill time: 3 sec or less. The foal was treated with emergency hydration, duphalyte, steroidal anti-inflammatory, atropine sulphate and antibiotic. After 6 h of treatment, the foal was stabilized and vital signs were normalized 8 h after treatment start.