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.     

Electrocardiographic Monitoring During Coloscopy

Electrocardiographic abnormalities were observed in 15 of 23 patients (65%), five with known heart disease, who were monitored for one hour prior to, during and for one hour after coloscopy. In one patient, ischemic S-T depression, 2 mm. below the resting level, persisted during the one hour following coloscopy. In all other patients, the electrocardiographic abnormalities disappeared before the end of the monitoring period.     

Intravenous calcitriol versus paricalcitol in haemodialysis patients with severe secondary hyperparathyroidism

Aim:   Secondary hyperparathyroidism (SHPT) is common among haemodialysis patients. Intensive treatment with calcitriol is often complicated by hypercalcaemia, hyperphosphataemia and elevated calcium phosphorus (Ca X PO₄) product. Paricalcitol is a vitamin D analogue developed to overcome some of the limitations of calcitriol therapy. The study objectives were to compare the response of intact parathyroid hormone (iPTH) and the incidence of hypercalcaemia, hyperphosphataemia and elevated Ca X PO₄ product in patients with severe SHPT treated with either i.v. calcitriol or i.v. paricalcitol.
Methods:   This was a single centre randomized open label study. Patients with serum intact iPTH of 50 pmol/L or more were randomized to receive either i.v. calcitriol (0.01 ug/kg) or i.v. paricalcitol (0.04 ug/kg) during every haemodialysis treatment. Serum iPTH, calcium, phosphorus and alkaline phosphatase were measured at the beginning of the study and every 3 weeks for 12 weeks.
Results:   Twenty-five patients were enrolled into the study – 12 were randomized into the calcitriol group and 13 into the paricalcitol group. There were no differences in the baseline study parameters between both groups. Serum iPTH levels were significantly reduced ( P  = 0.003) only in the paricalcitol group but not in the calcitriol group ( P  = 0.101). On the other hand, serum calcium levels were significantly increased only in the calcitriol group ( P  = 0.004 vs P  = 0.242). Serum phosphorus, alkaline phosphatase and Ca X PO₄ product were not different.
Conclusion:   Intravenous paricalcitol may be superior to i.v. calcitriol for the treatment of severe SHPT in our chronic haemodialysis population. A larger randomized controlled trial is indicated to confirm these initial findings.     

His Bundle Extrasystoles Revisited: The Great Electrocardiographic Masquerader

A 74‐year‐old man with past history of near syncope presented with frequent periods of second‐degree atrioventricular block (2° AVB). An electrophysiological study revealed prolonged atrial‐His and His‐ventricular (HV) intervals and frequent His bundle (H) extrasystoles. The latter manifested in the surface electrocardiogram as premature atrial, junctional, or ventricular beats, as well as 2° AVB that mimicked Wenckebach or Mobitz II block. Procainamide markedly suppressed H extrasystole. However, because of the presence of prolonged HV interval and history of presyncope, a permanent pacemaker was inserted. The case illustrates the varied manifestation of H extrasystole and presents guidelines for management. (PACE 2011; e56–e59)     

Endovascular Abdominal Aortic Aneurysm Repair by Interventional Cardiologists—A Community‐Based Experience

Introduction: Endovascular repair of abdominal aortic aneurysm (AAA) is a relatively recent technology. In comparison to the conventional open surgical treatment for AAA, endovascular AAA repair (EVAR) combines a less‐invasive approach with lower morbidity and mortality. There have been few studies regarding the performance of this procedure in a community‐based setting. We report our experience of EVAR performed primarily by interventional cardiologists in a community hospital. Methods: In our community hospital setting, between September 2005 and November 2007, we included all patients who underwent EVAR by interventional cardiologists, with available on‐site vascular surgical support. Clinical and serial computed angiographic imaging outcomes were followed by a retrospective chart review. Data collection tools included demographic and clinical characteristics, anatomical aneurysm features, length of stay, peri‐ and postprocedural complications, and mortality. Results: A total of 71 consecutive patients had EVAR attempted. The endovascular stent placement was successful in 67 (93%) patients. Thirty‐day mortality in this study was 1 of 71 (1.4%). All four procedural failures and the single periprocedural mortality occurred in women. Mean follow‐up was 12 months. There were a total of six mortalities and among these four were women (P ≤ 0.001); however, multivariate analysis revealed loss of significant difference in mortality (P = 0.16). Major complications following EVAR were noted in 10 of 71 (14%) patients. Conclusion: EVAR can be successfully performed by experienced interventional cardiologists with vascular surgical support in a community‐based setting. In our experience, there is acceptable rate of complications and mortality in a carefully selected patient population. (J Interven Cardiol 2010;23:485–490)     

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.