Assessment of frequency of micronucleated exfoliated buccal cells in relation to oxidative stress in oral lichen planus in coastal Karnataka,India

ObjectiveTo assess the frequency of micronucleus in exfoliated buccal mucosa cells of patients with oral lichen planus (OLP) in relation to free radical toxicity since OLP is considered to be a precancerous lesion.MethodsThe micronucleus frequency in exfoliated buccal mucosa cells of patients with OLP was assessed and compared to those in healthy subjects.ResultsA significant increase (P<0.004) in frequency of micronucleated exfoliated cells (MEC) was observed in patients with OLP when compared to normal subjects.ConclusionsIt can be concluded that DNA damage in MEC of OLP patients may be a consequence of increased free radical toxicity.     

Evaluation of left ventricular function and mass after Medtronic Freestyle versus homograft aortic root replacement using cardiovascular magnetic resonance

BACKGROUND AND AIM OF THE STUDY: Regression of left ventricular hypertrophy (LVH) after aortic valve replacement has traditionally been measured by echocardiography. However, cardiovascular magnetic resonance (CMR) can be used to measure left ventricular function and mass more accurately and reproducibly. This translates into fewer patients being needed to demonstrate significant changes. The study aim was to demonstrate the feasibility of using CMR to measure left ventricular mass index (LVMI) and function in patients from a prospective randomized trial, and to compare homografts with the Medtronic Freestyle root replacement. METHODS: Among 23 patients recruited, 17 had LVMI and function (end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and ejection fraction (EF)) measured pre- and postoperatively using CMR (eight homograft, nine Freestyle). RESULTS: Significant regression of LVH was seen in both groups one year postoperatively (homograft LVMI 145+/-44 g/m2 preoperative versus 83+/-23 g/m2 one year postoperatively; Freestyle LVMI 140+/-28 g/m2 versus 93+/-21 g/m2, respectively). At six months there was significant regression in the xenograft group (from 140+/-28 to 106+/-22 g/m2; p <0.05) and a trend towards regression in the homograft group (from 145+/-44 to 103+/-25 g/m2; p = NS). There was also a trend towards a reduction in EDV, ESV and SV, and an increase in EF over one year in both groups. CONCLUSION: Regression of LVH was measured using CMR in patients after aortic root replacement and coronary implantation with the homograft and Medtronic Freestyle root replacement. Despite the small number of patients studied, it was possible to demonstrate the extent and pattern of regression of left ventricular mass in the two groups.     

Measurement of ventricular volumes and function: a comparison of gated PET and cardiovascular magnetic resonance.

The aim of this study was to compare cardiac volume and function assessment using PET with the reference technique of cardiovascular magnetic resonance (CMR). METHODS: Left ventricular (LV) and right ventricular (RV) end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fractions (EF) were measured in 9 patients using both CMR and PET with inhaled C(15)O. RESULTS: Correlation between the techniques was generally reasonable (r values ranged from 0.63 to 0.99). Best agreement was seen for ESV (LV and RV). With PET, there was a tendency to underestimate LV EF and EDV, and RV EDV and SV. Agreement was worst for LV SV. Percentage difference between CMR and PET measurements ranged from -2% to 15%; Bland-Altman limits of agreement ranged from 24% to 75%. CONCLUSION: Although small systematic differences exist, the agreement between PET and CMR suggests useful information regarding function, and volumes may be obtained from a standard PET protocol.     

Inhibition of measles virus replication by 5'-nor carbocyclic adenosine analogues.

Despite intense efforts to increase vaccine coverage, measles virus (MV) still causes significant morbidity and mortality in the world, sometimes as the result of severe, chronic, lethal disease. In an effort to develop therapies to supplement immunization strategies, a number of 5'-nor carbocyclic adenosine analogues were evaluated for anti-MV activity in CV-1 monkey kidney cells. Of those compounds tested, those either unsubstituted at C4 or possessing a hydroxyl, azido or amino substituent at that position were the most active, with particularly significant inhibition of MV, strain Chicago-1. The EC50 values against this strain ranged from <0.1 to 1 mg/ml, as determined by cytopathic effect reduction assay, and confirmed by neutral red uptake. By virus yield reduction assay (+)-(1S,25,3R,4S)-4-(6'-amino-9'H-purin-9'-yl)cyclopentane-1,2,3-triol (2) (-)-(1R,2S,3R)-1-(6'-amino-9'H-purin-9'-yl)-2,3-dihydoxycyclopent-4-ene (3) (-)-(1R,2S,3R)-1-(6'-amino-9'H-purin-9'-yl)cyclopentane-2,3-dihydoxycyclopentane (5) and (-)-(1R,2R,3R,4S)-4-amino-1-(6'-amino-9'H-purin-9'-yl)cyclopentane-2,3-diol (8) were the most potent compounds tested, all with EC90 values of < or =0.4 mg/ml. Compounds 3 and 5 were also tested against other MV strains, and similarly inhibited those strains except for four designated as Bil, Edmonston, SA and X-1108. Compound 8 did not potently inhibit these other MV strains. In addition, 3, 5 and 8 demonstrated synergistic (additive) inhibition of MV replication in combination with ribavirin at several concentrations. Compounds 3, 5 and 8 were also potent MV inhibitors even when added to infected cells 24 h after virus exposure. None of these three compounds was virucidal at concentrations that inhibited viral replication as determined by virus yield reduction assay. Most compounds tested were also not toxic at concentrations >100 mg/ml in actively growing and stationary-phase cells. Results suggest that these compounds may be clinically useful anti-MV virus agents.     

Clinical,Immunological, and Molecular Findings of Patients with p47<Superscript>phox</Superscript> Defect Chronic Granulomatous Disease (CGD) in Indian Families

Chronic granulomatous disease (CGD) is a group of inherited disorder of phagocytes, resulting from mutations in the components of the NADPH oxidase complex. Reduced or absent oxygen radical synthesis seen in these patients leads to impaired killing of intracellular bacteria and fungi. CGD clinically presents with recurrent and life-threatening infections as well as granulomatous inflammatory responses. p47^phox encoded by the NCF1 gene is the most common autosomal recessive form of CGD which is often clinically milder. Here, we are presenting the data on clinical and immunological findings in 21 Indian patients with Del GT mutation in the NCF1 gene. Diagnosis of these patients was based on detailed clinical evaluation, measurement of respiratory burst activity by nitro blue tetrazolium and dihydrorhodamine-1,2,3 assay, expression of p47^phox by flow cytometry, and molecular confirmation by GeneScan method. Seventeen male and four female patients with median age of onset of 1 year ranging from 1.5 months to 6 years were included in the study. Sixty-two percent (13 out of 21) of patients belonged to a consanguineous marriage with only one family having a history of a previous sibling death. Significant variability in clinical presentation was observed in spite of identical genetic defect ranging from asymptomatic to very severe presentation leading to early death or requiring transplantation. However, none of these patients showed difference in immunological parameters to account for this variability. Thus, this study highlights the phenotypic heterogeneity seen in these patients with Del GT mutation in the NCF1 gene and its implication in management of these patients.     

QSAR analysis of indazole estrogens as selective beta-estrogen receptor ligands: rationalization of physicochemical properties

Quantification of structure activity relationships was performed on a series of indazole estrogen analogs, for their relative beta estrogenic receptor agonist activity, in order to understand the essential structural requirements for selectivity of indazole estrogen analogs for beta-estrogenic receptor over alpha-estrogenic receptor. The de novo and Hansch approach suggested that the 3(rd) position of indazole nucleus (R(1)) is decisive for the selectivity of molecules towards beta-estrogenic receptor over alpha-estrogenic receptor. The study also depicted that the substitution of polar group at R(1) position might prove helpful in the beta-estrogenic receptor selectivity (ER(beta/alpha )).     

Total nutritional capacity and inflammation inhibition effect of Acalypha alnifolia Klein ex wild—An unexplored wild leafy vegetable

Investigation of the nutritional as well as trace elements of a wild leafy vegetable, Acalypha alnifolia, and evaluation of the analgesic, anti-inflammatory, and antipyretic properties of acetone and methanol leaf extracts are the main objectives of the present study. The powdered A. alnifolia leaf sample was subjected to nutritional and mineral analysis. Plant leaves were extracted (using the Soxhlet apparatus) as successive solvent extractions. The extract doses of 200 and 400 mg/kg of acetone and methanol extracts were used for pharmacology study. The analgesic, anti-inflammatory, and antipyretic experiments were carried out by using animal models. The obtained result proves that the plant possesses essential nutritive values and useful biological properties. The higher dose of acetone extract has significant potency when compared with methanol extract at p < 0.005. On the whole, the plant is rich in minerals and has good biological properties; hence, this plant is suggested for cultivation and regular use for nutritional supplement.     

Antifungal drug susceptibility of Cryptococcus neoformans from clinical sources in Nairobi, Kenya

The serotypes and mating types of 80 clinical isolates of Cryptococcus neoformans from Kenya were studied and subjected to broth microdilution susceptibility testing to amphotericin B (AMP), flucytosin, fluconazole (FLC), itraconazole (ITC) and miconazole (MCZ). The isolates included C. neoformans var. grubii- 75 of 80 (serotype A; 93.7%), C. neoformans var. neoformans- three of 80 (3.8%) and C. neoformans var. gattii- two (serotype B; 2.5%). Mating experiment confirmed all the isolates to be alpha-mating type. Seventy-eight (97.5%) of the isolates had minimum inhibitory concentration (MIC) of < or =0.5 microg ml(-1) to AMP and at 1 microg ml(-1), 100% of the isolates were inhibited. Flucytosin resistance was observed in 21% with MIC in which 90% of the isolates were inhibited (MIC90) of 64 microg ml(-1). Only 23.8% of the strains were susceptible to FLC with 65% susceptible dose-dependent (SDD) and 11.2% resistant. Itraconazole susceptibility was 61.3% while the rest were either SDD or resistant. The MIC90 for ITC and MCZ were 0.5 and 2 microg ml(-1) respectively. The study reports the serotypes, mating types and highlights the existence of azoles resistance in C. neoformans in Nairobi which calls for antifungal drug resistance surveillance as prophylactic use of FLC increases because of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) epidemic in sub-Saharan Africa.     

Immunomodulatory analogues of thalidomide in the treatment of multiple myeloma

The design of innovative, more effective, less toxic therapy for multiple myeloma (MM) is emerging in parallel to a better understanding of the underlying pathophysiology of this common hematologic malignancy. Thalidomide has changed the treatment paradigm for patients with myeloma. Its efficacy, however, has been compromised to some degree by its side effects. Immunomodulatory drugs (IMiDs) are structural and functional analogues of thalidomide that were specifically designed to produce new agents with enhanced immunomodulating and anticancer properties but with less toxicity. In this article, we review the clinical trial development of second-generation IMiDs lenalidomide and CC-4047. Both agents demonstrate potent activity with manageable toxicities and provide another treatment opportunity for patients with MM.