ETHANOL ENHANCES MEDIAL AMYGDALOID INDUCED INHIBITION OF PREDATORY ATTACK BEHAVIOUR IN THE CAT: ROLE OF GABAA RECEPTORS IN THE LATERAL HYPOTHALAMUS

The present study tested the hypothesis that the suppressiveeffects of ethanol upon predatory attack behaviour in the catinvolve a pathway from the medial amygdala to the lateral hypothalamus,and that these suppressive effects are mediated by -aminobutyricacid (GABA_A receptors located in the lateral hypothalamus. Cannulaelectrodes were implanted into the lateral hypothalamus forelicitation of predatory attack behaviour and for microinjectionsof the GABA_A receptor antagonist, bicuculline. Monopolar stimulatingelectrodes were implanted into the medial amygdala from whichsubseizure levels of electrical stimulation suppressed predatoryattack behaviour. In the first phase of the study, we comparedresponse latencies for predatory attack behaviour followingsingle stimulation of the lateral hypothalamus alone with thosefollowing paired trials of dual stimulation of the medial amygdalaplus lateral hypothalamus. Dual stimulation significantly suppressedpredatory attack. In the second phase of the study, peripheralethanol administration (in doses of 0.01, 0.5 and 1.0 g/kg,i.p.) enhanced the suppressive effects of medial amygdaloidstimulation in a dose- and time-dependent manner in which peakeffects were obtained 60 min post-injection. In the third phaseof the study, bicuculline (0.15 nmol) was microinjected intothe lateral hypothalamus both prior to and following pairedtrials of dual stimulation. Drug infusion blocked the suppressiveeffects of medial amygdaloid stimulation upon predatory attackbehaviour elicited from the lateral hypothalamus, indicatingthe importance of GABA_A receptors in mediating this suppression.In the fourth phase of the study, bicuculline, microinjectedinto the lateral hypothalamus at the time when ethanol's effectswere maximal (i.e. 60–80 min post-ethanol administration),totally blocked the suppressive effects of medial amygdaloidstimulation as well as the enhancing effects of ethanol uponmedial amygdaloid suppression of this form of aggressive behaviour.In the last phase of the study, bicuculline (0.15 nmol) infusioninto the lateral hypothalamus significantly reduced the suppressiveeffects of ethanol (10g/kg, i.p.) upon predatory attack behaviourelicited from the lateral hypothalamus. These results supportthe hypothesis that ethanol's suppressive effects upon predatoryattack behaviour in the cat are mediated, at least in part,by GABA_A receptors in the lateral hypothalamus. The presentand recent findings in our laboratory support the view thatGABA_A receptors in the lateral hypothalamus are activated, inturn, by a GABAergic pathway which arises from the medial hypothalamuswhose neurons receive inputs from the medial amygdala.     

Interleukin-18 Antagonism Improved Histopathological Conditions of Malaria Infection in Mice

Background: Interleukin 18 (IL-18) exerts pleiotropic roles in many inflammatory-related diseases including parasitic infection. Previous studies have demonstrated the promising therapeutic potential of modulating IL-18 bioactivity in various pathological conditions. However, its involvement during malaria infection has yet to be established. In this study, we demonstrated the effect of modulating IL-18 on the histopathological conditions of malaria infected mice. Methods: Plasmodium berghei ANKA infection in male ICR mice was used as a model for malaria infection. Modulation of IL-18 release was carried out by treatment of malarial mice with recombinant mouse IL-18 (rmIL-18) and recombinant mouse IL-18 Fc chimera (rmIL-18Fc) intravenously. Histopathological study and analysis were performed on major organs including brain, liver, spleen, lungs and kidney. Results: Treatment with rmIL-18Fc resulted in significant improvements on the histopathological conditions of the organs in malaria-infected mice. Conclusion: IL-18 is an important mediator of malaria pathogenesis and targeting IL-18 could prove beneficial in malaria-infected host.Key Words: Malaria, Interleukin-18, Plasmodium berghei, Histopathology     

The Potential of β Carbolin Alkaloids to Hinder Growth and Reverse Chloroquine Resistance in Plasmodium falciparum

Background:

Nowadays, scourge of malaria as a fatalistic disease has increased due to emergence of drug resistance and tolerance among different strains of Plasmodium falciparum. Emergence of chloroquine (CQ) resistance has worsened the calamity as CQ is still considered the most efficient, safe and cost effective drug among other antimalarials. This urged the scientists to search for other alternatives or sensitizers that may be able to augment CQ action and reverse its resistance.

Method:

Three β-carbolin derivatives, namely, harmalin, harmol and harmalol were tested for their anti-plasmodial and CQ resistance reversal effects against P. falciparum 3D7 and K1. SYBRE Green-1 based drug sensitivity assay and isobologram analysis were used to screen the mentioned effects respectively.

Results:

All of them showed moderate anti-plasmodium effect and harmalin was the most effective as compared to the others in reversing CQ resistance and tolerance.

Conclusion:

The mentioned phytochemicals are not ideal to be used as conventional antimalarials and only harmalin can be suggested to reverse CQ resistance in P. falciparum K1.     

Initial Clinical Experience with the New Irrigated Tip Magnetic Catheter for Ablation of Scar-Related Sustained Ventricular Tachycardia: A Small Case Series

Background: A remote magnetic navigation system (MNS) has been used with a nonirrigated magnetic catheter for ablation of some supraventricular and ventricular arrhythmias. However, the irrigated tip catheter has not been evaluated.
Objective: To evaluate the feasibility and efficiency of the newly available irrigated tip magnetic catheter for radiofrequency ablation (RF) of electrical storm due to scar-related ventricular tachycardia (VT) in patients with ischemic heart disease.
Methods: Between January and March 2008, a total of 4 consecutive patients (4 men, mean age 67.7 years) with electrical storm who had an implantable cardioverter defibrillator underwent radiofrequency ablation using a remote MNS and the new magnetic irrigated catheter.
Results: Five ablation procedures were performed in study patients. Acute success, defined as noninducibility of any monomorphic VT, was obtained in 3 patients. In 1 patient, a nonclinical VT remained inducible. A monomorphic VT corresponding to clinical VT with the median (range) cycle length of 485 (440–580) ms was induced in all patients. The duration of ablation was 2,273 (985–3087) seconds, with median total procedure and fluoroscopy times of 135 (100–150) minutes and 6.5 (5–9) minutes, respectively. One recurrence occurred 1 week after ablation, which was ablated successfully in the second session. No complication was observed after ablation. During mean follow-up of 4.2 months, all patients were in sinus rhythm, they received no ICD therapy, and no mortality occurred.
Conclusions: Irrigated ablation of scar-related ventricular tachycardia guided by remote MNS is a feasible and effective modality for management of the electrical storm in patients with ischemic cardiomyopathy with minimal radiation exposure.     

Metastatic Carcinoma Simulating Linitis Plastica of the Colon

Reported herein is the case of a 70-year old woman with metastatic breast carcinoma presenting as linitis plastica of the ascending colon. The breast tumor was diagnosed nine years previously. The clinical, roentgenographic and pathologic features of colonic linitis plastica and the preoperative diagnostic difficulties are discussed. There is no difference in the morphologic features of primary and secondary linitis plastica. The latter may result from anaplastic carcinoma of the stomach, gallbladder or breast.     

Potential New Indication for Ivabradine: Treatment of a Patient with Congenital Junctional Ectopic Tachycardia

Ivabradine is a new antiarrhythmic agent with direct inhibition of the pacemaker (If) current. It has been used extensively to decrease sinus rate in the treatment of cardiac failure, and also in a single case of atrial ectopic tachycardia in a child. Here we report the case of a 3‐year‐old girl with congenital junctional ectopic tachycardia (JET), resistant to conventional antiarrhythmic medications, who was successfully treated with ivabradine. We suggest that ivabradine can be an effective treatment for junctional automatic tachycardias and can be considered as a new line of therapy for this incessant form of tachycardia.     

Permanent Cardiac Pacing with Sutureless Myocardial Electrodes: Experience in First One Hundred Patients

This report concerns our experience with a sutureless myocardial lead which we have used in 103 patients for establishment of permanent cardiac pacing. The electrode was inserted through a subxiphoid approach in all patients. Results to date indicate that this technique compares favorably with the presently popular transvenous technique as far as immediate or long-term morbidity is concerned. Complications were related entirely to pericardiotomy; no lead failure was seen during a maximum follow-up period of four years.     

Predictors of Syncope in Patients with Hypertrophic Cardiomyopathy

Background: Approximately 30% of patients with hypertrophic cardiomyopathy (HCM) suffer syncope and syncope was the only symptom associated with sudden death. However, no systematic studies in large cohorts looking at predictors of syncope are available in the literature. Therefore, we sought to determine predictors of syncope in patients with HCM.
Methods: One hundred and seventy-three consecutive patients with HCM and a mean age of 42 ± 18 years (range 10–78) underwent extensive clinical, electrocardiographic, and echocardiographic testing to identify predictors of syncope.
Results: During the mean follow-up duration of 50 months, syncope occurred in 28% of the HCM patients. Univariate analysis showed male gender, age <40 years, family history of sudden death, PR interval, QRS width, ≥2 bursts of nonsustained ventricular tachycardia (NSVT), ≥3 bursts of nonsustained supraventricular tachycardia (NSSVT), maximum left ventricular wall thickness ≥30 mm, and abnormal blood pressure response, out of 24 demographic, clinical, hemodynamic, electrocardiographic, and echocardiographic features, to be significantly associated with syncope. Of these nine variables, the only independent predictors of syncope at multivariate analysis were age <40 years (odds ratio [OR]: 4.4, 95% confidence interval [CI]: 2.2–16, P = 0.003), ≥2 bursts of NSVT (OR: 9.9, 95% CI: 2.0–46, P = 0.0001), and ≥3 bursts of NSSVT (OR: 2.7, 95% CI: 0.38–8.25, P = 0.001). The concomitant occurrence of all three variables had a sensitivity of 87% and specificity of 73% in identifying the patients with syncopal events.
Conclusions: The results of this study showed that age <40 years, bursts of NSVT, and NSSVT were independently associated with the risk of syncope in patients with HCM. Demographic data and ambulatory ECG findings could help in risk stratification of patients with HCM.     

Catheter Ablation of an Accessory Pathway within the Marshall Vein in a Patient with Mechanical Mitral Valve

A 37‐year‐old man, known case of mitral valve replacement, was referred for ablation. Meticulous mapping showed the earliest signal in the distal coronary sinus (CS). Endocardial ablation via transseptal approach failed to permanently ablate the accessory pathway. Similarly, ablation within the CS was unsuccessful. Finally, the mapping catheter was introduced into the vein of Marshall (VoM) and a very early signal was obtained. In the first 3 seconds of the radiofrequency energy application within the VoM, delta wave disappeared. During 1‐year follow‐up, the patient had no recurrence of the palpitations and electrocardiogram showed no delta wave. (PACE 2013; 36:e132–e135)