Recent advancements and new perspectives in animal models for Neurocysticercosis immunopathogenesis

Neurocysticercosis (NCC), one of the most common parasitic diseases of the central nervous system, is caused by Taenia solium. This parasite involves two hosts, intermediate hosts (pig and human) and a definitive host (human) and has various stages in its complex life cycle (eggs, oncosphere, cysticerci and adult tapeworm). Hence, developing an animal model for T. solium that mimics its natural course of infection is quite challenging. We have reviewed here the animal models frequently used to study immunopathogenesis of cysticercosis and also discussed their usefulness for NCC studies. We found that researchers have used mice, rats, guinea pigs, dogs, cats and pigs as models for this disease with varying degrees of success. Mice and rats models have been utilized extensively for immunopathogenesis studies due to their relative ease of handling and abundance of commercially available reagents to study these small animal models. These models have provided some very exciting results for in‐depth understanding of the disease. Of late, the experimentally/naturally infected swine model is turning out to be the best animal model as the disease progression closely resembles human infection in pigs. However, handling large experimental animals has its own challenges and limitations.     

Thirty-nine cases of pure red cell aplasia: A single center experience from India

Pure red cell aplasia (PRCA) is an uncommon disorder, characterized by transfusion dependent anemia, reticulocytopenia with selective aplasia or paucity of erythroid cells in bone marrow. There are only a few large series of PRCA reported in literature. This is the largest single center series of PRCA from India.

Objective: To evaluate the utility of Immunohistochemistty with Glycophorin A on bone marrow biopsies in quantitating the cut-off percentage of erythroid blasts required for diagnosis, as the upper cut-off percentage of erythroblasts for establishing a diagnosis of PRCA is still not clear.

Methods: The clinical data were obtained from patients' case files. Immunohistochemistry with Glycophorin A was performed using an immunoperoxidase technique and percentage of Glycophorin A positive cells of all nucleated cells was calculated by two independent observers.

Results: In our study, bone marrow aspirates showed a variable percentage of erythroblasts ranging from 2 to 12% (mean 6.3%) in children and from 1 to 8% (mean 4.6%) in adults on Giemsa smears. Immunohistochemistry (IHC) with Glycophorin A showed a mean positive cell % of 8.2 (range 2–16%) and 6.8 (1–9%) in pediatric and adult respectively against a mean of 28% (range 21–39%) in idiopathic thrombocytopenia (ITP) cases. Treatment with prednisone showed good response in a majority of both adults and childhood PRCA. Cyclosporine was found to be a good alternative in prednisone non-responders. Thymectomy was beneficial in patients with thymoma.

Conclusion: A higher percentage of erythroid cells (>5%) does not exclude a diagnosis of PRCA in an appropriate clinical setting and therefore can be managed as PRCA.     

Ileocolic mucormycosis – an unusual cause of a mass in the right iliac fossa

Mucormycosis is a relatively uncommon, aggressive and lethal mycosis. Fungi from the order Mucorales are the etiological agents of mucormycosis. The condition is more common among the immunocompromised, diabetic patients with ketoacidosis and people with iron overload syndromes. Diagnosis of mucormycosis requires a high index of suspicion regarding the possibility of the condition in high-risk individuals. Timely diagnosis is critical to survival and minimization of morbidity. A favourable outcome is possible only if appropriate treatment is initiated as early as possible. The present article reports a case of ileocolic mucormycosis involving a patient with chronic renal failure and familial hyperuricemia.     

In cirrhotic patients variceal bleeding is more frequent in the evening and correlates with severity of liver disease

BACKGROUND/AIMS: It has been observed that the portal pressure in cirrhotic patients shows circadian variation and is at a maximum at night. Our aims in this study were a) to evaluate the frequency of upper gastrointestinal (UGI) bleeding from esophageal/gastric varices or portal congestive gastropathy during the day, evening or night shift, and b) to correlate the frequency of bleeding during various shifts with severity of liver disease. METHODOLOGY: At our institution, during the period from January 1997 to June 1995, 15,000 gastrointestinal (GI) endoscopic reports and consultations were evaluated. Episodes of bleeding due to portal hypertension (PH), i.e., esophageal varices, gastric varices or congestive gastropathy, were noted. The time of occurrence of bleeding from PH in various shifts, e.g., day shift (DS), evening shift (ES) or night shift (NS) was determined. The severity of liver disease was classified as A, B or C according to Child's classification. RESULTS: There were 221 episodes of UGI bleeding due to PH in 144 patients. 75.5% of patients presented with hematemesis, whereas 24.5% presented with melena (p < 0.025). Bleeding started during the DS in 39/221 (17.6%), during the ES in 122/221 (55.2%), and during the NS in 60/221 (27.1%). There were 29 (13.1%) patients in Child's A, 75 (33.9%) in Child's B, and 117 (52.9%) in Child's C. Among the 122 bleeders during ES, 85 (69.6%) were in category C. It seems that in these patients UGI bleeding is more frequent during the ES compared to DS and NS (p < 0.0001; chi square; 95% CI: 0.52-0.58). Child's C patients are more likely to bleed during ES compared to Child's A or B patients (p < 0.0001; Odds Ratio: 4.8%; 95% CI: 2.7-8.5). CONCLUSIONS: 1) The majority of the cirrhotic patients with PH who develop UGI bleeding present with hematemesis rather than melena. 2) The bleeding in these patients is more likely to occur during the ES. 3) Child's C patients are more likely to bleed during the ES.     

Reduction of serum cholesterol and hypercholesterolemic atherosclerosis in rabbits by secoisolariciresinol diglucoside isolated from flaxseed

BACKGROUND: Secoisolariciresinol diglucoside (SDG) is a plant lignan isolated from flaxseed. Lignans are platelet-activating factor-receptor antagonists that would inhibit the production of oxygen radicals by polymorphonuclear leukocytes. SDG is an antioxidant. Antioxidants studied thus far are known to reduce hypercholesterolemic atherosclerosis. The objective of this study was to determine the effect of SDG on various blood lipid and aortic tissue oxidative stress parameters and on the development of atherosclerosis in rabbits fed a high-cholesterol diet. METHODS AND RESULTS: Rabbits were assigned to 4 groups: group 1, control; group 2, SDG control (15 mg. kg body wt-1. d-1 PO); group 3, 1% cholesterol diet; and group 4, same as group 3 but with added SDG (15 mg. kg body wt-1. d-1 PO). Blood samples were collected before (time 0) and after 4 and 8 weeks of experimental diets for measurement of serum triglycerides, total cholesterol (TC), and LDL, HDL, and VLDL cholesterol (LDL-C, HDL-C, and VLDL-C). The aorta was removed at the end of the protocol for assessment of atherosclerotic plaques; malondialdehyde, an aortic tissue lipid peroxidation product; and aortic tissue chemiluminescence, a marker for antioxidant reserve. Serum TC, LDL-C, and the ratios LDL-C/HDL-C and TC/HDL-C increased in groups 3 and 4 compared with time 0, the increase being smaller in group 4 than in group 3. Serum HDL-C decreased in group 3 and increased in group 4 compared with time 0, but changes were lower in group 3 than in group 4. SDG reduced TC and LDL-C by 33% and 35%, respectively, at week 8 but increased HDL-C significantly, by>140%, as early as week 4. It also decreased TC/LDL-C and LDL-C/HDL-C ratios by approximately 64%. There was an increase in aortic malondialdehyde and chemiluminescence in group 3, and they were lower in group 4 than in group 3. SDG reduced hypercholesterolemic atherosclerosis by 73%. CONCLUSIONS: These results suggest that SDG reduced hypercholesterolemic atherosclerosis and that this effect was associated with a decrease in serum cholesterol, LDL-C, and lipid peroxidation product and an increase in HDL-C and antioxidant reserve.     

Abnormal flow-mediated epicardial vasomotion in human coronary arteries is improved by angiotensin-converting enzyme inhibition: a potential role of bradykinin

OBJECTIVES: This study was performed to determine whether angiotensin converting enzyme (ACE) inhibition improves endothelium-dependent flow-mediated vasodilation in patients with atherosclerosis or its risk factors and whether this is mediated by enhanced bradykinin activity. BACKGROUND: Abnormal coronary vasomotion due to endothelial dysfunction contributes to myocardial ischemia in patients with atherosclerosis, and its reversal may have an antiischemic action. Previous studies have shown that ACE inhibition improves coronary endothelial responses to acetylcholine, but whether this is accompanied by improved responses to shear stress remains unknown. METHODS: In 19 patients with mild atherosclerosis, metabolic vasodilation was assessed during cardiac pacing. Pacing was repeated during separate intracoronary infusions of low-dose bradykinin (BK) and enalaprilat. Endothelium-dependent and -independent vasodilation was estimated with intracoronary BK and sodium nitroprusside respectively. RESULTS: Enalaprilat did not alter either resting coronary vascular tone or dilation with sodium nitroprusside, but potentiated BK-mediated dilation. Epicardial segments that constricted abnormally with pacing (-5+/-1%) dilated (3+/-2%) with pacing in the presence of enalaprilat (p = 0.002). Similarly, BK at a concentration (62.5 ng/min) that did not alter resting diameter in the constricting segments also improved the abnormal response to a 6+/-1% dilation (p < 0.001). Cardiac pacing-induced reduction in coronary vascular resistance of 27+/-4% (p < 0.001) remained unchanged after enalaprilat. CONCLUSIONS: Thus ACE inhibition: A) selectively improved endothelium-dependent but not-independent dilation, and B) abolished abnormal flow-mediated epicardial vasomotion in patients with endothelial dysfunction, in part, by increasing endogenous BK activity.     

Prognostic value of cardiovascular magnetic resonance in patients with suspected arrhythmogenic right ventricular cardiomyopathy

Background

Early recognition and accurate risk stratification are important in the management of arrhythmogenic right ventricular cardiomyopathy (ARVC). Identification of predictors of outcome by cardiovascular magnetic resonance (CMR) in patients undergoing evaluation for ARVC is limited. We investigated the predictive value of morphological abnormalities detected by CMR for major clinical events in patients with suspected ARVC.

Methods

We performed a longitudinal study on 369 consecutive patients with at least one criterion for ARVC. Abnormal CMR was defined by the presence of one of the following: increased right ventricular (RV) volumes, reduced RV ejection fraction, RV regional wall motion abnormalities, myocardial fatty infiltration, and myocardial fibrosis. The end-point was a composite of cardiac death, sustained ventricular tachycardia, ventricular fibrillation, and appropriate ICD discharge.

Results

Twenty patients met the composite end-point over a mean follow-up of 4.3 ± 1.5 years. An abnormal CMR was an independent predictor of outcomes (p < 0.001). The presence of multiple abnormalities heralded a particular high risk of events (HR 23.0, 95% CI 5.7–93.2, p < 0.001 for 2 abnormalities; HR 35.8, 95% CI 9.7–132.6, p < 0.001 for 3 or more abnormalities). The positive predictive value of an abnormal CMR study was 21.0% for an adverse event, whilst the negative predictive value of a normal CMR study was 98.8% over the follow-up period.

Conclusions

CMR provides important prognostic information in patients under evaluation for ARVC. A normal study portends a good prognosis. Conversely, the presence of multiple abnormalities identifies a high risk group of patients who may benefit from ICD implantation.