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     

A menopause-specific quality of life questionnaire: development and psychometric properties

Objective:

to develop a condition-specific quality of life questionnaire for the menopause with documented psychometric properties, based on women's experience. Methods: Subjects: Women 2–7 years post-menopause with a uterus and not currently on hormone replacement therapy. Questionnaire development: A list of 106 menopause symptoms was reduced using the importance score method. Replies to the item-reduction questionnaire from 88 women resulted in a 30-item questionnaire with four domains, vasomotor, physical, psychosocial and sexual, and a global quality of life question. Psychometric properties: A separate sample of 20 women was used to determine face validity, and a panel of experts was used to confirm content validity. Reliability, responsiveness and construct validity were determined within the context of a randomized controlled trial.Construct validation involved comparison with the Neugarten and Kraines' Somatic, Psychosomatic and Psychologic subscales, the reported intensity of hot flushes, the General Well-Being Schedule, Channon and Ballinger's Vaginal Symptoms Score and Libido Index, and the Life Satisfaction Index.

Results:

The face validity score was 4.7 out of a possible 5. Content validity was confirmed. Test-retest reliability measures, using intraclass correlation coefficients were 0.81, 0.79, 0.70 and 0.55 for the physical, psychosocial, sexual domains and the quality of life question. The intraclass correlation coefficient for the vasomotor domain was 0.37 but there is evidence of systematic change. Discriminative construct validity showed correlation coefficients of 0.69 for the physical domain, 0.66 and 0.40 for the vasomotor domain, 0.65 and −0.71 for the psychosocial domain, 0.48 and 0.38 for the sexual domain, and 0.57 for the quality of life question. Evaluative construct validity showed correlation coefficients of 0.60 for the physical domain, 0.28 for the vasomotor domain, 0.55 and −0.54 for the psychosocial domain, 0.54 and 0.32 for the sexual domain, and 0.12 for the quality of life question. Responsiveness scores ranged from 0.78 to 1.34.

Conclusions:

The MENQOL (Menopause-Specific Quality of Life) questionnaire is a self-administered instrument which functions well in differentiating between women according to their quality of life and in measuring changes in their quality of life.     

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.     

Parental involvement and spousal satisfaction with division of early childcare in Turkish families with normal children and children with special needs

In this low-income Turkish sample, parents reported on father and mother division of childcare labor and satisfaction with division. Regardless of whether they were rearing typical or atypical children, mothers reported a higher level of involvement than fathers in every domain of childcare. In general, both mothers and fathers reported slight dissatisfaction with their own level of participation in childcare. Across groups, all mothers were significantly more dissatisfied (than their spouses were with their level of participation) with the fathers' level of participation in childcare. Best predictors of parental involvement were parent's employment status, satisfaction with partner level of involvement, and parent educational level.     

Initiation of sexual intercourse among middle school adolescents: the influence of psychosocial factors.

PURPOSE: To explore potential psychosocial predictors for initiation of sexual intercourse among middle-school, inner-city youth, using longitudinal data from the Healthy and Alive! project. METHODS: We conducted hierarchical, logistic regression with adjustment for intraclass correlation over two sequential periods, including seventh and eighth grades (N = 3163), to assess the independent influence of psychosocial and demographic factors. Internally reliable scales to assess psychosocial influences were created, based on major theories of behavior. The sample was 52% female, 51% black, 30% Hispanic, 9% white, and 3% Asian. At baseline, 13% of girls and 39% of boys reported already having initiated sexual intercourse. RESULTS: Personal and perceived peer norms about refraining from sex were a strong and consistent protective factor. Alcohol and other drug use, poor academic performance, male gender, and black race were consistent risk factors. Self-efficacy showed a mixed effect: protective in the seventh grade but increasing risk in the eighth grade. Speaking a language other than English was a protective factor in seventh grade. Both psychosocial and demographic factors provided independent explanatory power. CONCLUSIONS: Psychosocial factors, particularly norms about having sex, influence initiation of sexual intercourse. These data suggest that programs to delay initiation of sexual intercourse should reinforce norms about refraining from sex.     

Cross-neutralization of the neurotoxicity of Crotalus durissus terrificus and Bothrops jararacussu venoms by antisera against crotoxin and phospholipase A2 from Crotalus durissus cascavella venom.

We have previously demonstrated that rabbit antisera raised against crotoxin from Crotalus durissus cascavella venom (cdc-crotoxin) and its PLA2 (cdc-PLA2) neutralized the neurotoxicity of this venom and its crotoxin. In this study, we examined the ability of these antisera to neutralize the neurotoxicity of Crotalus durissus terrificus and Bothrops jararacussu venoms and their major toxins, cdt-crotoxin and bothropstoxin-I (BthTX-I), respectively, in mouse isolated phrenic nerve-diaphragm preparations. Immunoblotting showed that antiserum to cdc-crotoxin recognized cdt-crotoxin and BthTX-I, while antiserum to cdc-PLA2 recognized cdt-PLA2 and BthTX-I. ELISA corroborated this cross-reactivity. Antiserum to cdc-crotoxin prevented the neuromuscular blockade caused by C. d. terrificus venom and its crotoxin at a venom/crotoxin:antiserum ratio of 1:3. Antiserum to cdc-PLA2 also neutralized the neuromuscular blockade caused by C. d. terrificus venom or its crotoxin at venom or toxin:antiserum ratios of 1:3 and 1:1, respectively. The neuromuscular blockade caused by B. jararacussu venom and BthTX-I was also neutralized by the antisera to cdc-crotoxin and cdc-PLA2 at a venom/toxin:antiserum ratio of 1:10 for both. Commercial equine antivenom raised against C. d. terrificus venom was effective in preventing the neuromuscular blockade typical of B. jararacussu venom (venom:antivenom ratio of 1:2), whereas for BthTX-I the ratio was 1:10. These results show that antiserum produced against PLA2, the major toxin in C. durissus cascavella venom, efficiently neutralized the neurotoxicity of C. d. terrificus and B. jararacussu venoms and their PLA2 toxins.     

Pharmacological evidence for a presynaptic action of venoms from Bothrops insularis (jararaca ilhoa) and Bothrops neuwiedi (jararaca pintada).

Whereas the presynaptic action of Crotalus durissus terrificus venom is well-established, Bothrops venoms have historically been considered to have only postsynaptic and muscular effects. However, some studies have also suggested a presynaptic action for these venoms. In this work, we used chick biventer cervicis preparations to compare the presynaptic actions of two Bothrops venoms (B. insularis and B. neuwiedi) with that of C. d. terrificus venom. At 10 microg/ml, all venoms produced irreversible blockade of the twitch tension responses, with no reduction in acetylcholine (ACh)-induced contractures and only a slight decrease in potassium induced-contractures. The times (in min) required to produce 50% neuromuscular blockade (C. d. terrificus: 16.3+/-0.7, n = 8; B. insularis: 30.0+/-1.9, n = 5; B. neuwiedi: 42.0+/-2.0, n = 8; mean +/- SEM) were significantly different among the venoms (p < 0.01). Lowering the temperature at which the experiments were done (from 37 to 24 degrees C) prevented neuromuscular blockade by the three venoms, indicating that enzyme activity may be involved in this response. At concentrations capable of causing complete neuromuscular blockade, creatine kinase release remained close to levels seen in control preparations incubated with Krebs solution alone (500-1200 IU/l). Commercial crotalic antivenom, but not bothropic antivenom, protected against the neuromuscular blockade caused by B. insularis and B. neuwiedi venoms. These observations indicate that bothropic venoms may contain components which act presynaptically in a manner similar to C. d. terrificus venom, and that at low venom concentrations a direct action on skeletal muscle does not contribute to this presynaptic neurotoxicity.