Antifungal Activity of a New Triterpenoid Glycoside from Pithecellobium racemosum (M.)

Purpose. In a continuation of our search for novel antifungal compounds from higher plants, the standard extract of the bark of Pithecellobium racemosum was found to have good activity against important AIDS-related opportunistic yeasts. Methods. The extract was subjected to bioguided fractionation using silica gel column chromatography which led to purification of triterpene glycosides. The structures of these compounds were determined by a combination of spectroscopic (IR, NMR, HRMS) and chemical methods. Results. Compound 1 is a new glycoside, 3-O[-L-arabinopyranosyl (1 -2)][-L arabinopyranosyl (1 -6)]2-acetoamido-2-deoxy--D-gluco-pyranosyl oleanolic acid and Compound 2 was identified as the known compound 3-O-[-L-arabinopyranosyl (l-2)]-L-arabinopyranosyl (1-6)] 2-acetamido-2-deoxy--D-glucopyranosyl echinocystic acid. Conclusions. Compound 1 is a new glycoside, 3-O-[-L-arabinopyranosyl (1-2)]-L-arabinopyranosyl (l-6)]-2-acetoamido-2-deoxy--D-glucopyranosyl oleanolic acid and exhibits moderate antifungal activity against T. mentogrophytes, C. albicans and S. cerevisiae with MIC values of 6.25, 12.5 and 12.5 g/ml respectively.     

Basic neuroscience

Poster Session 1

Basic neuroscience     

Risk factors for cervical dysplasia in Kerala, India

A study in Kerala, India, confirmed the importance of genital hygiene in the fight against infections that have a role in the development of cervical dysplasia and cancer. Many women cannot afford sanitary pads, while adequate facilities for washing after coitus are often unavailable. Health education, satisfactory living standards, and the empowerment of women are prerequisites for reducing the incidence of cervical dysplasia.     

A prospective comparative study of MR sialography and conventional sialography of salivary duct disease

OBJECTIVE: The purpose of this study was to determine the diagnostic accuracy of MR sialography in the examination of patients with salivary duct disease. SUBJECTS AND METHODS: Forty-nine patients (23 males and 26 females; 16-78 years old; mean age, 47 years) with symptoms related to the salivary glands underwent both conventional sialography and MR sialography. The latter was performed using a heavily T2-weighted, two dimensional, fast spin-echo technique and a 12-cm circular surface coil. Contiguous 3-mm axial images with frequency-selective fat suppression were acquired through the symptomatic gland. The MR sialography findings were compared with the final diagnoses determined by conventional sialography. RESULTS: Conventional sialography showed calculus disease (n = 13), stricture (n = 12), sialectasis (n = 4), cast (n = 3), neoplasm (n = 2), and normal duct (n = 16). MR sialography alone had a sensitivity of 69% in revealing calculus disease. However, the sensitivity increased to 100% when MR sialograms were combined with control radiographs. MR sialography was sufficient to accurately reveal stricture, sialectasis, and neoplasm and to direct therapy on the basis of its findings. Overall, MR sialography combined with control radiographs had a sensitivity, specificity, and diagnostic accuracy of 100%, 88%, and 96%, respectively, in revealing salivary duct abnormalities. CONCLUSION: MR sialography alone is not sufficiently sensitive to reveal salivary duct stones. Caution must be exercised when excluding calculus disease. MR sialography, when combined with control radiographs, is accurate and has the potential to replace conventional sialography.     

Immunosuppression is not required for reactivation of latent murine cytomegalovirus

We have shown, for the first time, that TNF induces expression of MCMV IE RNA in the lungs of latently infected mice in the absence of immunosuppression. These initial data suggest that TNF may play an important role in the reactivation of latent MCMV, in the absence of immunosuppression, and provide a provocative insight into the mechanisms of CMV reactivation. Studies are in progress to determine whether genes associated with later stages of the viral life cycle are induced by TNF and whether infectious virus is produced.     

Role of sialylation in determining the pharmacokinetics of neutrophil inhibitory factor (NIF) in the Fischer 344 rat

1. Recombinant neutrophil inhibitory factor (NIF) is a glycoprotein. Its amino acid sequence remains constant and has a molecular weight of 28.9 kD. However, approximately 40% of the total molecular weight consists of glycans with variable structure. 2. The pharmacokinetics of 11 different NIF batches with varying extents and patterns of sialylation have been investigated in the Fischer 344 rat following intravenous administration. These data indicate that reducing the extent of NIF sialylation reduces the half-life of the molecule due to an increase in the systemic clearance. Also, an increase in the number of unsialylated or neutral glycans may increase the volume of distribution of NIF, although this effect is marginal. 3. Isolated perfused rat liver (IPRL) investigations have shown that sialylated NIF has a low hepatic extraction (< 1%), while asialo NIF has an extraction that is > 20-fold higher. Co-administration of asialo NIF with asialo fetuin (a protein cleared by hepatic asialoglycoprotein receptor (possibly galactose)-mediated uptake reduced the hepatic extraction of asialo NIF. 4. These data suggest that NIF molecules that have free sugar moieties (possibly galactose) interact with an asialoglycoprotein receptor (possibly galactose-mediated) in the liver (parenchymal cells/hepatocytes). Interaction with this receptor leads to cellular internalization and degradation.     

Biophysical, histopathological and pharmacological characterization of crotamine isoforms F22 and F32.

Two major crotamine isoforms (F22 and F32) were obtained after three chromatographic steps and were assayed in mouse phrenic nerve-diaphragm preparations. F32 and F22 (0.5 microg/ml, n=4) produced a facilitatory effect, which increased isometric twitch-tension by 300 and 230%, respectively, after a 120 min incubation. At a concentration of 0.1 microg/ml, both isoforms increased the twitch-tension by about 160%. However, when the isoforms were co-incubated (final concentration, 0.5 microg/ml) for 30 min prior to testing, they did not cause the facilitation seen with > or =0.1 microg/ml of each isoform alone. Histologically, F32 and F22 at 0.5 and 1 microg/ml were quantitatively alike in inducing tissue myonecrosis. However, a mixture of the two isoforms (final concentration, 0.5 microg/ml) significantly attenuated the damage seen with either toxin alone. Mass spectrometry analysis showed that the isoforms had the same molecular mass (4.8 kDa) and that they existed as monomers with a highly stable structure. These results indicate that F22 and F32 acted on muscle cells of the mouse phrenic-nerve diaphragm preparation through similar mechanisms. Since the isoforms did not produce the expected summation in the increase in muscle twitch-tension, it is possible that they may have different affinities for the sodium channel subunits.     

Health status and quality of life in patients with early-stage Hodgkin's disease treated on Southwest Oncology Group Study 9133.

PURPOSE: We describe the short and intermediate-term quality-of-life (QOL) outcomes in patients treated on a randomized clinical trial in early-stage Hodgkin's disease (Southwest Oncology Group [SWOG] 9133) comparing subtotal lymphoid irradiation (STLI) with combined-modality treatment (CMT). PATIENTS AND METHODS: Two hundred forty-seven patients participated in the QOL study (SWOG 9208), completing several standardized instruments (Symptom Distress Scale; Cancer Rehabilitation Evaluation System - Short Form; Medical Outcomes Study 36-Item Short-Form Health Survey Vitality Scale; and a health perception item), as well as questions about work, marital status, and concerns about having children. This article reports on results from baseline before random assignment, at 6 months, and at 1 and 2 years after random assignment. RESULTS: Patients receiving CMT experienced significantly greater symptom distress (P <.0001), fatigue (P =.001), and poorer QOL (P =.015) at 6 months than the STLI patients, reflecting a shorter time since completion of therapy in the CMT arm. Importantly, patients in the two groups did not differ on any outcomes at the 1-and 2-year assessments. Both patient groups reported significantly more fatigue before treatment than healthy reference populations, and fatigue did not improve in either group after treatment. CONCLUSION: This study demonstrated that patients with early-stage Hodgkin's disease experience a short-term decrease in QOL and an increase in symptoms and fatigue with treatment, which is more severe with CMT; by 1 year, however, CMT and STLI patients report similar outcomes. Fatigue scores for both arms were lower at baseline than scores for the general population and did not return to normal levels 2 years after random assignment. The mechanisms responsible for this lingering problem warrant further investigation.     

The relationship between dietary fat intake and risk of colorectal cancer: evidence from the combined analysis of 13 case-control studies

The objective of this study was to examine the effects of the intakeof dietary fat upon colorectal cancer risk in a combined analysis of datafrom 13 case-control studies previously conducted in populations withdiffering colorectal cancer rates and dietary practices. Original datarecords for 5,287 cases of colorectal cancer and 10,470 controls werecombined. Logistic regression analysis was used to estimate odds ratios (OR)for intakes of total energy, total fat and its components, and cholesterol.Positive associations with energy intake were observed for 11 of the 13studies. However, there was little, if any, evidence of anyenergy-independent effect of either total fat with ORs of 1.00, 0.95, 1.01,1.02, and 0.92 for quintiles of residuals of total fat intake (P trend =0.67) or for saturated fat with ORs of 1.00, 1.08, 1.06, 1.21, and 1.06 (Ptrend = 0.39). The analysis suggests that, among these case-control studies,there is no energy-independent association between dietary fat intake andrisk of colorectal cancer. It also suggests that simple substitution of fatby other sources of calories is unlikely to reduce meaningfully the risk ofcolorectal cancer.