This study was designed to obtain information potentially of value in understanding an modifying the impact of the social environment of the perceived quality of like among institutionalized aged persons. It was hypothesized that Person-Environment (P-E) congruence, as assessed by the Environmental Perception, Preference and Importance Scale (EPPIS), would be related to (1) sex integration/segregation makeup of the health related facility (HRF) living units, and (2) quantity of social interaction between staff and residents. Analysis of sex by unit sex-type interaction for 60 residents' Person-Environment (P-E) congruence scores revealed that elderly females on sex-integrated units reported a higher level of P-E congruence than those residing on female-only units; males on sex-integrated units, in contrast, reported a poorer level of P-E congruence than males on sex -segregated units. Furthermore, behavioral observations of staff-resident verbal interactions confirmed the hypothesis that residents living on units with high staff-resident interaction perceived the environments more congruent with their preferences than residents on units low in verbal interaction. The observed relationships between the P-E congruence measure, resident-staff interaction, and unit sex-type were taken as further support for the relevance and value of the EPPIS measure as a tool for assessing and improving the institutional milieu.

The present concepts on histamine releasing factors are discussed, their cellular origins, their effect on the target cells and its importance in asthma immunopathology. Personal results on the production of HRF by alveolar macrophages stimulated by allergen and its action on non atopic basophils are presented. Alveolar macrophages from atopic asthmatics release HRF in presence of allergen. Macrophage from non atopic do not. HRF has been tested in a Human Basophil Degranulation Test (HBDT) preparation, a significant degranulation induced by HRF from atopic patient being only observed when atopic basophils are used in HBDT. These results confirm that allergen could induce HRF production from alveolar macrophages and that this HRF could degranulate basophils in atopic and induce mediators release.

Diisocyanate-induced asthma differs from occupational asthma (OA) caused by protein allergens in that specific IgE antibody responses are rarely identified. To investigate the immunopathogenesis of diisocyanate asthma, diisocyanate-exposed workers were evaluated for in vitro production of antigen-specific mononuclear cell-derived histamine releasing factor (HRF). The mean HRF response to diisocyanate-HSA antigens was significantly greater in patients with OA than in diisocyanate-exposed asymptomatic subjects (p < 0.05). No association was found between HRF and diisocyanate-specific antibodies. Analysis of HRF production by subpopulations of peripheral blood mononuclear cells (PBMC) showed that lymphocytes and adherent cells were major sources of both spontaneous and antigen-stimulated HRF. The results suggest that antigen-specific HRF produced by PBMCs are an important biomarker for diisocyanate-induced asthma. This is the first report of hapten-specific stimulation of PBMCs resulting in HRF production.

BACKGROUND

Congenital heart malformations are risk factors that make children susceptible to infections resulting in inflammation.

METHODS

The concentration of histamine as a modulator of inflammation was quantified in pericardial fluid and expression of histamine H(4) receptor (H(4)R) and histamine-releasing factor (HRF) was determined at mRNA and protein levels. Samples of pericardium and pericardial fluid were obtained during cardiac reconstruction surgery in children.

RESULTS

In children with pericarditis, increased levels of histamine were found and expression of H(4)R was localized on mast cells. Expression of HRF was independent of presence or absence of inflammation in pericardium and was localized within stationary epithelial cells.

CONCLUSIONS

Results indicate that involvement of H4R in pericardial inflammation depends on penetration of mast cells into inflamed tissue, but HRF may not be directly involved in inflammatory reaction of the pericardium.

Histamine-releasing factor (HRF) consists of a group of cytokines that can cause basophil/mast cell to release histamine, however, the composition of HRF still remains undefined. This study was designed to measure the concentrations of chemokines in asthmatic children receiving immunotherapy. Peripheral blood mononuclear cells culture supernatants were obtained from six asthmatic children before and four, eight months after immunotherapy (IT). The levels of monocyte chemotactic and activating factor (MCAF), macrophage inflammatory protein-1a (MIP-1a), regulated on activation normal T-cell expressed and secreted (RANTES) and interleukin-8 (IL-8) spontaneously and after stimulation with PHA and mite allergen in the supernatants. The data showed: 1) The levels of MCAF and MIP-1a increased four months, and decreased eight months, after IT; 2) By contrast, the level of RANTE increased after IT; 3) The level of IL-8 also tended to increase after IT. Abnormal chemokine production may contribute to the pathogenesis of bronchial asthma and restoration of normal chemokine production may be used to partially explain the clinical efficacy of immunotherapy.

Purposes of the study were (1) to investigate changes in physical performance during 6 years follow-up among high-functioning older adults and (2) to describe the selection of study sample with reference to measured performance. Subjects (n=1,133) born during 1917-1941 participated in the battery of health-related fitness (HRF) tests (6.1-m walk, stair climbing, backwards walk, trunk side-bending, dynamic back extension, 1-km walk and body mass index) in 1996. Six hundred and six subjects were retested in 2002. In general, poorer fitness in the baseline assessment predicted non-participation in retesting as well as test exclusions and interruptions in retesting. The 6-year changes in the HRF showed a linear trend (P<0.01) according to age group: performance of older groups deteriorated on average more than the performance of younger groups. In most of the tests, gender was statistically significantly (P<0.05) associated with the changes in performance. The mean performance of the women deteriorated in all tests during the follow-up, while the mean performance of the men deteriorated only in the trunk side-bending, 6.1-m walk and 1-km walk tests. It can be concluded that among the subjects who participated in the follow-up testing, older age and being a woman increased deterioration in several components of HRF. Considering the selection of the subjects, the deteriorations identified are very likely underestimations of real fitness changes among this sample.

BACKGROUND

Diabetic retinopathy (DRP) is a common microvascular complication seen in patients with type 1 diabetes mellitus (T1DM). The effects of T1DM and concomitant (proliferative) DRP on retinal blood flow are currently unclear. Therefore, we measured retinal vascular blood flow in T1DM patients with and without DRP and non-diabetic controls. We further assessed the acute effects of panretinal photocoagulation on retinal microvascular bloodflow in eight patients with diabetes.

METHODS

Thirty-three T1DM patients with proliferative DRP, previously treated with panretinal photocoagulation (pDRP), 11 T1DM patients with untreated non-proliferative retinopathy (npDRP) and 32 T1DM patients without DRP (nDRP) were compared with 44 non-diabetic gender-matched controls. Using scanning laser Doppler flowmetry (HRF, Heidelberg) blood flow in the retinal microvasculature was measured temporal and nasal of the optic disc and averaged into one flow value per eye. The right eye was used as a default for further analyses. Eight patients with novel proliferative retinopathy (4 T1DM and 4 with type 2 diabetes) were measured before and several months after photocoagulation. Between-group differences in retinal blood flow were assessed using ANOVA corrected for multiple comparisons (Bonferroni).

RESULTS

Retinal blood flow was higher in the treated pDRP compared with the nDRP group and controls (all P Bonferroni < 0.01). Furthermore, there was a positive linear trend for blood flow with lowest blood flow in the control group and highest in the pDRP group (P-for-trend < 0.01). In the eight patients with novel proliferative retinopathy, blood flow did not significantly change before and after panretinal photocoagulation (P>> 0.05). Using regression analysis, no variables were found as predictors of retinal blood flow.

CONCLUSIONS

In comparison with controls and nDRP patients, retinal blood flow significantly increased in the pDRP group, which previously underwent photocoagulation treatment, but not in the npDRP patients. These changes may be a consequence of a failing vascular autoregulation in advanced diabetic retinopathy.

BACKGROUND

To determine if patients with no contact with a multi-disciplinary team High Risk Foot Service (MDT-HRFS) had an increased rate of hospital admission for diabetes foot infection compared to patients with contact. Secondary aims were to report on clinical outcomes.

METHODS

A retrospective study was conducted at a major tertiary referral hospital in metropolitan Sydney over 12 months. An ICD-10 search of the electronic medical record system and paper medical charts identified patients with diabetes mellitus (type 1 or type 2) and a primary admission for diabetes foot infection (DFI). Patients were categorised as having contact or no contact with an MDT-HRFS.

RESULTS

One hundred ninety-six hospital admissions (156 patients) were identified with DFI over a 12-month period. Patients with no contact with a MDT-HRFS represented three quarters of admissions (no contact = 116, 74.7 % vs. contact = 40, 25.6 %, p = 0.0001) and presented with more severe infection (no contact = 39 vs. contact = 12). The odds of lower extremity amputation increased five-fold when both no contact and severe infection occurred in combination (no contact with severe infection and amputation = 34, 82.9 % vs. contact with severe infection and amputation = 7, 17.1 %, OR 4.9, 95 % CI 1.1-21.4, p = 0.037). Using estimates of both the contact and no contact population of people with diabetes and high-risk feet and assuming the risk of amputation was the same, than the number of expected amputations in the no contact group should have been 55, however the observed number was 77, 22 more than expected (p = 0.0001).

CONCLUSIONS

Patients with no contact with a MDT-HRFS represented the majority of admissions for DFIs to a tertiary referral hospital. This group on population estimates appears to be at high risk of amputation of the lower extremity and therefore early referral of this high-risk group might lower this risk.

Two simple, sensitive and specific high-performance thin-layer chromatographic (HPTLC) methods were developed for the determination of febuxostat (FEB) individually, and simultaneously with diclofenac (DIC) in human plasma. Method A presents the first HPTLC-ultraviolet attempt for FEB determination in human plasma. FEB was separated from endogenous plasma components (at hRF = 70) with ethyl acetate-methanol-water (9:2:1, v/v) mixture as mobile phase and quantified by densitometry at its λmax (315 nm). Method B is considered the first attempt for the simultaneous determination of FEB and DIC in human plasma. A mixture of petroleum ether-chloroform-ethyl acetate-formic acid (7.5:1:2.5:0.25, v/v) was used as the mobile phase. The two drugs were separated at hRF of 39 and 60 for FEB and DIC, respectively. FEB and DIC were quantified by densitometry at their isoabsorptive point (289 nm). FEB calibration plots were linear between 0.1 and 7 μg mL-1 in both methods A and B. In method B, DIC showed linear response in the range of 0.08-8 μg mL-1. Sample preparation was performed by liquid-liquid extraction using diethyl ether. Both methods did not record any interference from plasma matrix, the studied drugs' metabolites or their decomposition products. They were successfully applied for the determination of the studied drugs in healthy male volunteers after oral administration of FEB or FEB/DIC dosage forms. FEB plasma concentration increased significantly when given with DIC. The proposed methods provided very simple, rapid and cheap approaches that might be attractive for the future pharmacokinetic and bioavailability studies of FEB and/or DIC.

Currently, there is no method for providing a nonverbal objective assessment of pain. Recent work using functional near-infrared spectroscopy (fNIRS) has revealed its potential for objective measures. We conducted two fNIRS scans separated by 30 min and measured the hemodynamic response to the electrical noxious and innocuous stimuli over the anterior prefrontal cortex (aPFC) in 14 subjects. Based on the estimated hemodynamic response functions (HRFs), we first evaluated the test-retest reliability of using fNIRS in measuring the pain response over the aPFC. We then proposed a general linear model (GLM)-based detection model that employs the subject-specific HRFs from the first scan to detect the pain response in the second scan. Our results indicate that fNIRS has a reasonable reliability in detecting the hemodynamic changes associated with noxious events, especially in the medial portion of the aPFC. Compared with a standard HRF with a fixed shape, including the subject-specific HRFs in the GLM allows for a significant improvement in the detection sensitivity of aPFC pain response. This study supports the potential application of individualized analysis in using fNIRS and provides a robust model to perform objective determination of pain perception.

Soil aquifer treatment (SAT) using primary effluent (PE) is an attractive option for wastewater treatment and reuse in many developing countries with no or minimal wastewater treatment. One of the main limitations of SAT of PE is rapid clogging of the infiltration basin due to high suspended solid concentrations. Some pre-treatment of PE before infiltration is likely to reduce this limitation, improve performance of SAT and help to implement this technology effectively. The effects of three pre-treatment options namely sedimentation (SED), coagulation (COAG) and horizontal roughing filtration (HRF) on SAT were analyzed by conducting laboratory-scale batch and soil column experiments. The sedimentation and coagulation pre-treatments led to less head loss development and reduction of clogging effect. The head loss development in soil column using PE + COAG and PE + SED was reduced by 85 and 72%, respectively, compared to PE alone without any pretreatment. The overall dissolved organic carbon (DOC) removal of pre-treatments and soil column collectively were 34, 44, 51 and 43.5% for PE without any pre-treatment, PE + SED, PE + COAG and PE + HRF, respectively. Coagulation pre-treatment of PE was found to be the most effective option in terms of suspended solids, DOC and nitrogen removal. Sedimentation pre-treatment of PE could be attractive where land is relatively less expensive for the construction of sedimentation basins.

Purpose: American Society of Clinical Oncology (ASCO) guidelines define high-risk prognostic features (HRFs) in stage II colon cancer and recommend limiting adjuvant chemotherapy to patients with HRFs. We evaluated the extent to which HRFs influenced decisions on adjuvant chemotherapy before and after publication of the guidelines. Patients and Methods: We reviewed data from 100 consecutive patients with stage II colon cancer resected between January 2000 and June 2007. Practice pattern in the pre-guideline era (2000 through 2004) was compared with the postguideline era (2005-2007). Results: The median age of the cohort was 65.8 years. A total of 60 patients had>>/= 1 HRF. Overall, 38% of the patients with HRFs did not receive chemotherapy; 37.5% without HRFs did. Seventy-one percent of the patients given adjuvant chemotherapy had HRFs versus 48% of the patients not given chemotherapy. There was no association between the presence/absence of HRFs and chemotherapy (P = .25). The association between number of HRFs per individual and chemotherapy was significant (P = .0255). Bowel obstruction and T4 disease were the only individual HRFs significantly associated with chemotherapy (P = .0059 and .0294, respectively). A significant drop in use of chemotherapy for all patients occurred after publication of the guidelines, but this was caused mostly by a drop in treatment for patients with HRFs from 80% to 36% (P = .001). Conclusion: Decisions for or against adjuvant chemotherapy did not adhere completely to ASCO guidelines. Publication of the guidelines led to a significant drop in appropriate use of adjuvant chemotherapy in high-risk patients.

OBJECTIVE

American Society of Clinical Oncology (ASCO) guidelines define high-risk prognostic features (HRFs) in stage II colon cancer and recommend limiting adjuvant chemotherapy to patients with HRFs. We evaluated the extent to which HRFs influenced decisions on adjuvant chemotherapy before and after publication of the guidelines.

METHODS

We reviewed data from 100 consecutive patients with stage II colon cancer resected between January 2000 and June 2007. Practice pattern in the pre-guideline era (2000 through 2004) was compared with the post-guideline era (2005-2007).

RESULTS

The median age of the cohort was 65.8 years. A total of 60 patients had>> or = 1 HRF. Overall, 38% of the patients with HRFs did not receive chemotherapy; 37.5% without HRFs did. Seventy-one percent of the patients given adjuvant chemotherapy had HRFs versus 48% of the patients not given chemotherapy. There was no association between the presence/absence of HRFs and chemotherapy (P = .25). The association between number of HRFs per individual and chemotherapy was significant (P = .0255). Bowel obstruction and T4 disease were the only individual HRFs significantly associated with chemotherapy (P = .0059 and .0294, respectively). A significant drop in use of chemotherapy for all patients occurred after publication of the guidelines, but this was caused mostly by a drop in treatment for patients with HRFs from 80% to 36% (P = .001).

CONCLUSIONS

Decisions for or against adjuvant chemotherapy did not adhere completely to ASCO guidelines. Publication of the guidelines led to a significant drop in appropriate use of adjuvant chemotherapy in high-risk patients.

Recurrent Respiratory Papillomatosis is a highly recurrent and residual disease. The use of indigo-carmine chromoendoscopy increases the early detection of nonvisible disease and reduces the possibility of leaving residual lesions. The best chances of papillomatosis being eradicated depend upon a surgical shallow epitheliolysis approach applied to patients who have never been surgically damaged before. We developed a novel surgical technique based upon the use of a time controlled High Radiofrequency (HRF) energy output. We applied a three-step bloodless HRF-surgical technique, that is, epitheliolysis, angiolysis and peeling without the aid of adjunct therapies. It acts according to differences in the water density of the tissues. We use it to remove the epithelial viral reservoir thus preserving subepithelial layers. For this purpose, we designed and manufactured a custom-made HRF electrodes set for office and O.R. use. From 2005 to 2018, 39 patients (100%) with recurrent respiratory papillomatosis participated in the present prospective work. Twenty-five (64,10%) achieved complete postsurgical remission, 6 (15,38%) were lost to follow up, and 8 (20,51%) present partial remissions. Thirty-six patients had laryngeal papillomatosis. Follow-up was possible in 30 of the 36 patients with laryngeal papillomatosis with a success remission rate of 83,33% (25 of 30). Eleven of those 36 (30,55%) entered this study without previous surgical treatment and 9 of 11 (81,81%) were cured. Indigo-carmine chromoendoscopy, a visualization solution for papillomatosis detection, together with a bloodless HRF-surgical technique proved to be effective tools to eradicate papillomatosis. Voice restoration to normal or near normal levels was achieved in all patients.

We tested dried East-Asian mushrooms that have only recently appeared on the German drug "scene". They were impregnated with lysergic acid diethylamide (LSD) but sold as Mexican sacred hallucinogenic mushrooms, containing psilocybine. For the safe identification of psilocybine in mushrooms, TASmethod is proposed. Successful identification of LSD in mushrooms is done by tartaric acid extraction with subsequent TLC of the free base. The modified van Urk reaction in connection with hRf-values is best suited for the detection of psilocybine, psilocine and LSD.

The WHO annually reports an increasing abuse of new psychoactive substances (NPS), which are a heterogeneous group of synthetic drugs and are consumed as substitute for controlled drugs of abuse. In this work, we focused on highly potent derivatives such those of phenethylamine (2C), N-2-methoxybenzyl phenethylamine (NBOMes), lysergic acid diethylamide (LSD), and fentanyl. Severe to fatal intoxications were described due to their high potency. Therefore, they have to be taken at very low doses resulting in low blood concentration in the low ng/mL range, which is a challenge for reliable analytical detection and quantification. The aim of this work was therefore to design a simple, robust, and fast method for simultaneous detection and quantification of multiple substances of the different classes in human blood plasma using liquid chromatography (LC) high resolution (HR) mass spectrometry (MS) with alternating HR full-scan (HRFS) MS and "All-ions fragmentation" (AIF) MS. The paper contains results of the method validation according to the EMA guideline, including intra-/interday accuracy and precision, matrix effects, storage and benchtop analyte stability as well as selectivity and carryover. All validation criteria were fulfilled for most tested compounds except for the NBOMe derivatives, one out of ten 2C-derivatives and butyryl fentanyl, which failed at accuracy and/or precision or at the acceptance criteria for matrix effect. Reasons for this are discussed and solutions presented. Despite some limitations, the HRFS + AIFMS analysis allowed detection of most of the analytes down to 0.1ng/mL, seamless integration of new or unexpected analytes, identification and quantification with no limitations on the number of monitored compounds, and reevaluation of the acquired data also concerning metabolism studies using group-indicating fragment ions.

Aortic regurgitation (AR) causes an increased diastolic reverse flow at various levels of aorta and its branching vessels. A prospective study was designed to evaluate the feasibility and accuracy of duplex sonography of the common carotid artery (CCA) in patients with various degrees of AR quantified by cardiac angiography. Twenty-four patients, with pure angiographic AR, of mean age 63.5 + 2.5-year old were included. Holodiastolic reverse flow (HRF) was recorded in all seven patients with severe angiographic AR (five with grade III and two with grade IV) and in none of the seventeen patients (eight with grade I and nine with grade II) with mild angiographic AR (p < 0.001). Furthermore, HRF was recorded both in the CCA and in the aorta, where it represents another criterion of severe AR, of six patients with severe angiographic AR and was absent in the eleven patients with grade I or II AR (p < 0.001). Demonstration of HRF in the CCA may be a very helpful criterion in distinguishing patients with severe AR.

OBJECTIVE

To discuss the prognostic significant of autophagy related proteins (ARPs) in retinoblastoma (RB) and to find the molecular marker to distinguish retinocytoma (RC) and RB by investigating the different expression profiling of microtubule-associated protein light chain 3 (LC3B) and other ARPs in RC and RB.

METHODS

Specimens with retinocytoma region (RCR) or mainly composed with Flexner-Winterstein rosettes (FWR) were screen out from 219 paraffin-embedded RB samples and respectively taken as RCR group and FWR group. Others were taken as undifferentiated (UD) group. Immunochemistry (IHC) of LC3B and electronic microscopy was used to identify autophagy. The IHC scores of LC3B and other ARPs, such as Beclin, PTEN, p27, p16(INK4a), mTOR and BCL-2 were compared and correlation analysis was applied to find potential proteins which may involve in autophagy regulation. The prognostics significance of LC3B was evaluated by comparing the high risk features (HRFs) in 3 groups of total 219 samples.

RESULTS

Twenty-one specimens with RCR and 36 specimens mainly composed with FWR were screen out. RCR cell had a high level of LC3B and lots of autophagic vacuoles. Beclin, PTEN, p27 had positive correlation with LC3, and p16(INK4a) had negative correlation, while the expression of mTOR and BCL-2 in RCR and RB region did not show any difference. Cases with RCR had lower rate of HRFs than undifferentiated cases.

CONCLUSIONS

ARPs had different expression pattern between RCR and other pathological types of RB, and could be ideal markers to distinguish RC from RB. Our finding indicated cases with RCR had favorable prognosis just like those with FWR.

This study examined the relationship between fundamental movement skills (FMS) and health related fitness (HRF) components in children. A cross section of Irish primary school children across all age groups participated in this study (n=2098, 47% girls, age 5-12 years of age, mean age 9.2 ±2.04). FMS were measured using the Test of Gross Motor Development (TGMD-3), along with two additional assessments of vertical jump and balance. All HRF components were also assessed: body composition through BMI and waist circumference, muscular strength (MS) using a hand dynamometer, muscular endurance (ME) through the plank test, flexibility with back-saver sit-and-reach, and cardiovascular endurance (CVE) using the 20m PACER test. Hierarchal multiple regressions were used to measure associations between the HRF components and overall FMS and the FMS subtests: locomotor, object control and balance skills. Results show significant positive relationships between FMS and MS (R² = 0.25, β= -0.19), ME (R² = 0.11, β= 0.34), flexibility (R² = 0.13, β= 0.14) and CVE (R² = 0.17, β= 0.39), and an inverse relationship between FMS and body composition (R² = 0.25, β= -0.19). The data presented reinforces the position that the relationship between FMS and HRF is dynamic, and predominantly strengthens with age through the course of childhood. Findings suggest that developing FMS as a child may be important to developing HRF across childhood and into adolescence.

Keywords: Motor skills; children’s health; physical activity.

OBJECTIVE

To isolate the cardiogenic fraction, which can enhance cardiogenic differentiation of bone marrow-derived mesenchymal stem cells (MSC) from Geum japonicum. The therapeutic effect of the isolated cardiogenic fraction was further tested in a rat myocardial infarction (MI) model.

METHODS

Bioassay guided fractionation method was used for the isolation of the cardiogenic fraction, named as heart repair fraction (HRF). MI was induced by a permanent ligation of left anterior descending coronary artery. The rats exhibiting similarly decreased values of left ventricle ejection fraction (LVEF) and fraction shortening (LVFS) were used. The rats in test group (n = 10) were subject to HRF treatment (20 mg×kg(-1)×d(-1)) through gastric gavage daily for 4 weeks. Water alone (2 ml/d) was given through gastric gavage to rats in the control group (n = 10). The cardiac function was assessed by echocardiography at different time points. Masson trichrome staining was used for evaluation of the infarct size. Morphological and immunohistochemical studies were performed to investigate the HRF mediated myocardial regeneration.

RESULTS

LVEF (66.2% ± 6.9%) and LVFS (46.8% ± 5.8%) were significantly increased two weeks post HRF treatment compared with the values (LVEF: 55.7% ± 6.0% and LVFS: 36.4% ± 5.2%) in control rats (all P < 0.01). The improved heart function was further restored 4 weeks post HRF treatment (P < 0.01). Furthermore, the treatment of acute MI with this HRF significantly reduced the infarct size (19.0% ± 6.1%) compared with that (31.1% ± 8.6%) in control rats (P < 0.01). Substantial regeneration of cardiomyocytes in infarcted region of the HRF treated heart was also observed that replaced a considerable part of the infarcted heart tissues resulting in remarkable reduction of the infarct size.

CONCLUSIONS

The properties of this HRF isolated from Geum japonicum in stimulating substantial regeneration of myocardium in infarct region with consequently improved cardiac function appear to be new and represent a new approach for the treatment of MI.

Cattle losses in Brazil have been attributed to Palicourea marcgravii St. Hil., a toxic plant for cattle. The crude extract from the leaves of P. marcgravii was successively fractionated using solvents with different polarities to determine whether monofluoroacetic acid and/or some other substance present in the leaves may be responsible for the acute symptoms caused by the plant. Authentic sodium monofluoroacetate (SMFA) was used for comparison. The only P. marcgravii fraction which induced seizures and death in intoxicated rats was water soluble. The signs and symptoms induced in the animals by the crude extract and water-soluble fraction were the same as induced by SMFA and included tonic seizures and other actions on the CNS. The dose-lethality and dose-latency to the 1st seizure curves constructed for the water-soluble fraction of the leaf extract (30-100 mg/kg) and SMFA (0.6-3.0 mg/kg) were parallel. Five animals per dose were used. The potency ratio of SMFA in relation to the water-soluble fraction of the leaf extract was 53.8 (dose-lethality curve) and 64.1 (dose-latency to the 1st seizure curve). The water-soluble fraction contained a substance with hRf = 20 which was the same as that of authentic SMFA. The 19F NMR spectra of authentic SMFA and the P. marcgravii water-soluble fraction were identical. These data demonstrate the presence of SMFA in the water-soluble fraction of P. marcgravii leaves and show that monofluoroacetate is the active principle responsible for the signs and symptoms of acute intoxication.

OBJECTIVE

Among other neuroimaging techniques, functional magnetic resonance imaging (fMRI) can be useful for studying the development of motor fatigue. The aim of this study was to identify differences in cortical neuronal activation in nine subjects on three motor tasks: right-hand movement with minimum, maximum, and post-fatigue maximum finger flexion.

METHODS

fMRI activation maps for each subject and during each condition were obtained by estimating the optimal model of the hemodynamic response function (HRF) out of four standard HRF models and an individual-based HRF model (ibHRF).

RESULTS

ibHRF was selected as the optimal model in six out of nine subjects for minimum movement, in five out of nine for maximum movement, and in eight out of nine for post-fatigue maximum movement. As compared to maximum movement, a large reduction in the total number of active voxels (primary sensorimotor area, supplementary motor area and cerebellum) was observed in post-fatigue maximum movement.

CONCLUSIONS

This is the first approach to the evaluation of long-lasting contraction effort in healthy subjects by means of the fMRI paradigm with the use of an individual-based hemodynamic response. The results may be relevant for defining a baseline in future studies on central fatigue in patients with neuropathological disorders.