Identification and quantification of key phytochemicals in peas - Linking compounds with sensory attributes.

Pea protein isolates contain high-quality plant protein. However, they have sensory drawbacks, notably bitterness and astringency, that have limited their use in commercial foods. This study's aim was thus to identify the main phytochemicals in pea-based samples and to examine associations with sensory attributes. The phytochemical profiles of pea flour, pea protein isolates, and pea protein isolate fractions were characterized via UHPLC-DAD-MS. A total of 48 phytochemicals have been revealed: 6 phenolic acids, 5 flavonoids, and 1 saponin were identified and quantified, while another 9 phenolic acids, 10 flavonoids, and 6 saponins were tentatively identified. The impacts of protein extraction and fractionation were studied. These processes appear to have caused some compound degradation. It was found that 29 compounds were correlated with perceived bitterness and/or astringency. Therefore, these results show that certain phytochemicals can lead to negative sensory attributes in pea-protein-based products.

[Severe form of hereditary neuralgic amyotrophy without SEPT9 gene mutation]. / Névralgie amyotrophiante héréditaire à forme sévère sans mutation du gène SEPT9.

INTRODUCTION: Hereditary neuralgic amyotrophy (HNA) is a rare condition characterized by recurrent episodes of painful paralysis preferentially affecting the brachial plexus. It is often linked to a mutation in the SEPT9 gene. CASE REPORT: A 69-year-old female patient experienced a dozen episodes of severe neurological deficit mainly affecting the brachial plexus and the phrenic and recurrent nerves. The diagnosis of HNA without SEPT9 gene mutation was retained. DISCUSSION: HNA can have significant sequelae. A genetic heterogeneity exists and mutations in the SEPT9 gene may not be found. Immunomodulatory and corticosteroid treatments have sometimes proved to be effective.

An MRI comparison of anatomical changes related to surgical treatment of prolapse by vaginal or abdominal route.

PURPOSE: The aim of this study was to determine whether or not abdominal or vaginal access is the best choice for treating genital prolapse in term of anatomical postoperative results, using an MRI pre and postoperative assessment. MATERIALS AND METHODS: Prospective study was conducted on 43 consecutive patients planned for surgery for genital prolapse from October 2001 to February 2002. The patients were studied with dynamic and static MRI sequence 4 months after surgery to indicate surgical effects on organ position. The position was evaluated with respect to the pubo coccygeal line in a dynamic sequence. RESULTS: Fifteen patients had their prolapse corrected by laparotomy always associated with sub-total hysterectomy, anterior and posterior prosthetic mesh with promontory fixation to the prevertebral ligament. Sixteen others were subjected to vaginal route with vaginal hysterectomy, paravaginal suspension followed in all cases by suspension of the vaginal cuff using Richter's technique and myorraphy of the levators. Finally, 12 patients benefited from a suspension of a sacrospinous suspension and myorraphy of the levators, without paravaginal suspension. Measure of the MRI organ location showed no significant difference except for bladder position in vaginally operated women (P = 0.02). Vaginal length and axis were comparable in all groups. CONCLUSION: Our study confirmed the objective effectiveness of the anatomical prolapse corrections conducted by abdominal route using sacropexy or by vaginal route using sacrospinous fixation. The correction provided by vaginal route always results in a return of the bladder and the vaginal fundus to their normal positions, which clearly demonstrates the short-term effectiveness of these surgical suspensions. Prolapse corrections by vaginal route did not result in any shortening of the vagina or postoperative change in vaginal orientation. Further evaluations will be needed to assess the long-term results.

[Topographic and functional anatomy of cranial nerves]. / Atteintes périphériques des nerfs crâniens: anatomie.

This review summarizes the descriptive anatomy of cranial nerves III through XII, starting at their emergence from the neuraxis towards peripheral territories, as well as their functional anatomy. For each pair of cranial nerves, correlations are made between diseases, anatomo-clinical and anatomo-neurophysiological data.

Arterial vascularization of the human thalamus: extra-parenchymal arterial groups.

The problem of the arterial vascularization of the human thalamus has been debated at length. Anatomical references concerning the thalamic arterial groups are contradictory and complex, preventing any solid application in practice. It is, therefore, difficult to produce reliable anatomical radio-clinical correlation. In this work, 12 adult human cerebellums (24 hemispheres) were dissected after intra-vascular injection. With care for clarification and standardization, the extra-parenchymal thalamic arteries were classified in six groups: pre-mamillary artery, perforating thalamic arteries, thalamo-geniculate arteries, perforating branches of the postero-medial, postero-lateral and anterior choroidal arteries. Variations in the pre-mamillary artery were rare. The origin of the perforating thalamic artery was unilateral in two of three cases. The origin of the thalamo-geniculate arteries arose between the posterior cerebral artery (53%) and the posterior choroidal arteries (43%). The postero-median choroidal artery was most often single and usually gave the perforating branches for the medial aspect of the thalamus. The postero-lateral choroidal artery was frequently multiple and essentially gave the perforating branches for the superior aspect of the thalamus. The pulvinarian branches most often rose from the postero-lateral choroidal arteries (two thirds of cases) and more rarely from the postero-median choroidal arteries (one third of cases). The anterior choroidal artery is a source of thalamic vascularization by its cisternal branches running towards the lateral thalamus. It can also participate in the vascularization of the pulvinar by the plexiform branches crossing the temporal horn of the lateral ventricle. This study has allowed definition of the intra-parenchymatous arterial map of the thalamus. This mapping is essential for producing anatomical radio-clinical correlations which are pertinent for therapeutic decisions.

[Detrusor-sphincter dyssynergia and botulinum toxin]. / Dyssynergie vésico-sphinctérienne et toxine botulique.

OBJECTIVE: Botulinum toxin (BT) injection into the external urethral sphincter is a promising therapy for neurogenic voiding disorders due to detrusor-sphincter dyssynergia (DSD). However the optimal treatment protocol remains unclear. METHOD: A PubMed reference search and manual bibliography review were performed, along with a search in the Annales de réadaptation et de médecine physique and in the reports of the International French-language Society of Urodynamics and the International Continence Society, which allowed us to select twelve pertinent articles with PubMed, two articles from the Annales and two conference reports. Our analysis gave special emphasis to assessment criteria, application, dosage and BT injection technique. RESULTS: Used for the first time in 1988 in spinal cord injury patients to reduce outflow obstruction due to DSD, BT injections have been shown to be a valuable alternative management of bladder dysfunction with DSD. They have been proposed in neurological patients unable to perform self-catheterisation, after drug failure and before surgery. Parameters for results assessment are mostly clinical (increased free interval between voiding, decreased post-void residual urine volumes), urodynamic (improvement in bladder emptying, increase in functional bladder capacity and decrease in urethral pressure) and electromyographic (denervation of striated urethral sphincter). The literature data regarding type of BT, dosage and protocol vary widely. Duration of action is from 2 to 12 months. Both transurethral and transperineal injections monitored by EMG are equally effective in improving detrusor-sphincter dyssynergia. CONCLUSION: With few side effects and satisfactory medium-term results, BT should be recommended as a component of DSD therapies. We propose a practical method for BT use.

[Sialorrhea, hyperhidrosis and botulinum toxin]. / Hypersialorrhée, hypersudation et toxine botulique.

OBJECTIVE: The first clinical studies indicate that Botox provides effective treatment for hyperhidrosis and sialorrhea. The aim of this work is to sum up current evaluation of this use. METHOD: A systematic literature search was conducted on the Pub Med database, along with on chapters in other publications. The most interesting articles in relation to our own personal experience were chosen. RESULTS: Despite recent use of BT to treat focal hyperhidrosis, there have been numerous publications since 1997. However, the injected areas have not been listed so frequently. Axillary hyperhidrosis has been studied most; it is also in this case and in the case of gustatory sweating that the best results have been obtained. Publications about palmar and especially plantar hyperhidrosis are much rarer, almost anecdotic. It has been demonstrated to a lesser extent that BT injections are effective in these cases. Literature about sialorrhea is just beginning. However, the reduction of the production of saliva following intra parenchymatic injection of toxin into the parotid and submandibular glands, thus rarifying drooling, has been demonstrated. For each of the pathological indications, both the injection techniques and the optimal doses remain to be determined. DISCUSSION: Because BT blocks all cholinergic transmission, including the autonomous nervous system, it was plausible to expect a reduction in sweating and salivation on local injection of the product. In fact, the first publications indicated such efficiency without serious side effects. For hyperhidrosis, there has developed a consensus for making intracutaneous injections only. Of the injections in axillary areas, the palms of the hands, the plantar regions, the face or other cutaneous areas, palmoplantar hyperhidrosis is the least accessible, in any case causes the most technical problems, because of difficulty in pain management. For sialorrhea and the drooling that accompanies certain chronical neurological diseases, BT seems to have very promising effects. However, it has not been precisely determined whether to inject the parotid gland, the submandibular gland, or both. Necessary and sufficient means of targeting are still imprecise. It also remains to be determined the number of sites per gland and the doses to be injected.

[EMG support in botulinum toxin treatment]. / Apport de l'EMG dans l'utilisation de la toxine botulique.

INTRODUCTION: The aim of this work is to sum up how the use of EMG improves BT therapy. METHOD: A systematic review of the literature in the Pub Med computer database, along with a manual biography, allowed us to choose the most synthetic and the most pertinent publications according to our own practical experience. RESULTS: There is no consensus of opinion, but the great majority of authors emphasize the importance of EMG in the different stages of botulinum toxin treatment: before injections, at the time of the injection, and finally during the follow-up after the first injection or after the repeated injections that transient efficiency make necessary. DISCUSSION: A symptomatic therapeutic means recently recognized in focal dystonias and spasticity, BT is injected locally into the muscles to be treated. EMG can be used: at pre-injection for physiopathological evaluation but above all to establish a diagnosis and precise pre-intervention evaluation; at the moment of injection to provide guidance in precise muscle selection and for maximum efficiency with reduced, therefore less costly, doses. It also limits the risk of product diffusion susceptible of causing iatrogenic side effects and/or auto-immunisation resulting in resistance to the toxin; during follow-up, to understand why treatment failed and to look for changes in the dystonia pattern leading to objective re-evaluations and adapted reinjections. Although neglected by some, electrological logistics seem to us, as to many other practitioners who inject, to be a considerably helpful aid, particularly at the moment of injection when targeting the muscle to be treated.

[Acute polyradiculoneuritis during primary herpes simple virus infection]. / Polyradiculoneuropathie aiguë au cours d'une primo-infection à virus Herpès simplex.

The herpes virus family, particularly cytomegalovirus and Epstein-Barr virus, are often associated with acute polyradiculoneuritis (APRN). APRN following primary herpes simplex virus infection is much more uncommon, viral reactivation generally being involved. We report a patient who developed APRN following herpes simplex virus primary infection, probably HSV II.

Increased Trypanosoma cruzi invasion and heart fibrosis associated with high transforming growth factor beta levels in mice deficient in alpha(2)-macroglobulin.

Trypanosoma cruzi proteinases are involved in host cell invasion in human patients and in mouse models. In mice, murine alpha(2)-macroglobulin (MAM) and murinoglobulin are circulating plasma proteinase inhibitors that also have important roles in inflammation and immune modulation. To define their role in experimental Chagas disease, we investigated the susceptibility to T. cruzi infection of mice that are deficient only in alpha2-macroglobulins (AM-KO) or in both MAM and monomeric murinoglobulin-1 (MM-KO), relative to the wild type (WT). Despite the high parasite load, parasitemia was lower in AM-KO and MM-KO mice than in WT mice. Nevertheless, we observed a significantly higher parasite load in the hearts of AM-KO and MM-KO mice, i.e., more amastigote nests and inflammatory infiltrates than in WT mice. This result demonstrates a protective role for MAM in the acute phase of murine T. cruzi infection. We further demonstrated in vitro that human alpha2-macroglobulins altered the trypomastigote morphology and motility in a dose-dependent way, and that also impaired T. cruzi invasion in cardiomyocytes. Finally, we demonstrated that the levels of transforming growth factor beta in AM-KO mice increased significantly in the third week postinfection, concomitant with high amastigote burden and important fibrosis. Combined, these in vivo and in vitro findings demonstrate that the MAM contribute to the resistance of mice to acute myocarditis induced by experimental T. cruzi infection.

Significant association between the skewed natural antibody repertoire of Xid mice and resistance to Trypanosoma cruzi infection.

The Xid mutation predominantly affects the development of B cells and consequently the levels and composition of natural antibodies in sera. In contrast to the congenic and susceptible BALB/c strain, immunodeficient BALB.Xid mice display a resistant phenotype both to acute Trypanosoma cruzi infection and to the development of severe cardiopathy. Because natural antibodies are known to be basically self-antigen driven, IgM and IgG natural antibody repertoires (NAR) were compared before and during infection in these two strains. The analysis revealed fundamental alterations of IgM and IgG NAR in pre- and post-infected Xid mice. In particular, relatively increased natural (pre-existing) autoreactive IgG, dominated by the unique recognition of a single band in autologous heart extracts, was typical for uninfected Xid mice. This natural autoreactive IgG directed to heart antigens disappeared early after infection not only in Xid, but also in individual BALB/c mice that survived the acute infection. Conversely, the subgroup of BALB/c mice that died early after infection presented the most pronounced instances of the rapid, relative increase of IgM reactivities to self and non-self proteins. These results suggest that self-reactive NAR may play a role in an immunoregulatory mechanism relevant for the determination of susceptibility/resistance to infections. This may act either by influencing specific responses, or by modulating the self-aggressive components responsible for pathology.

High incidence of biallelic point mutations in the Runt domain of the AML1/PEBP2 alpha B gene in Mo acute myeloid leukemia and in myeloid malignancies with acquired trisomy 21.

The AML1 gene, situated in 21q22, is often rearranged in acute leukemias through t(8;21) translocation, t(12;21) translocation, or less often t(3;21) translocation. Recently, point mutations in the Runt domain of the AML1 gene have also been reported in leukemia patients. Observations for mutations of the Runt domain of the AML1 gene in bone marrow cells were made in 300 patients, including 131 with acute myeloid leukemia (AML), 94 with myelodysplastic syndrome (MDS), 28 with blast crisis chronic myeloid leukemia (CML), 3 with atypical CML, 41 with acute lymphoblastic leukemia (ALL), and 3 with essential thrombocythemia (ET). Forty-one of the patients had chromosome 21 abnormalities, including t(8;21) in 6 of the patients with AML, t(12;21) in 8 patients with ALL, acquired trisomy 21 in 17 patients, tetrasomy 21 in 7 patients, and constitutional trisomy 21 (Down syndrome) in 3 patients. A point mutation was found in 14 cases (4.7%), including 9 (22%) of the 41 patients with AML of the Mo type (MoAML) (none of them had detectable chromosome 21 rearrangement) and 5 (38%) of the 13 myeloid malignancies with acquired trisomy 21 (1 M1AML, 2 M2AML, 1 ET, and 1 atypical CML). In at least 8 of 9 mutated cases of MoAML, both AML alleles were mutated: 3 patients had different stop codon mutations of the 2 AML1 alleles, and 5 patients had the same missense or stop codon mutation in both AML1 alleles, which resulted in at least 3 of the patients having duplication of the mutated allele and deletion of the normal residual allele, as shown by FISH analysis and by comparing microsatellite analyses of several chromosome 21 markers on diagnosis and remission samples. In the remaining mutated cases, with acquired trisomy 21, a missense mutation of AML1, which involved 2 of the 3 copies of the AML1 gene, was found. Four of the 7 mutated cases could be reanalyzed in complete remission, and no AML1 mutation was found, showing that mutations were acquired in the leukemic clone. In conclusion, these findings confirm the possibility of mutations of the Runt domain of the AML1 gene in leukemias, mainly in MoAML and in myeloid malignancies with acquired trisomy 21. AML1 mutations, in MoAML, involved both alleles and probably lead to nonfunctional AML1 protein. As AML1 protein regulates the expression of the myeloperoxidase gene, the relationship between AML1 mutations and Mo phenotype in AML will have to be further explored. (Blood. 2000;96:2862-2869)

Expression of the multidrug resistance-associated protein in myelodysplastic syndromes.

In the myelodysplastic syndromes (MDS), P-glycoprotein (P-gp) expression is clinically associated with drug resistance, whereas the clinical significance of multidrug resistance-associated protein (MRP1) is uncertain. Bone marrow from 56 patients with MDS, including six with refractory anaemia (RA)/RA with ringed sideroblasts (RARS), 23 cases of RA with excess blasts/in transformation (RAEB/T), four patients with chronic myelomonocytic leukaemia (CMML) and 23 cases of MDS having progressed to acute myeloid leukaemia (MDS-AML), were studied. MRP1 expression was investigated by immunocytochemistry (ICC) and by flow cytometry using MRPm6 monoclonal antibody. The efflux test using calcein-AM (CAM) +/- probenecid to evaluate MRP1 activity was performed in ten of the 56 patients. Twenty-eight of the 56 cases (50%) expressed MRP1. MRP1 expression was more frequent in MDS-AML than in MDS (70% vs. 36%). The efflux test using CAM was positive in three out of the ten patients tested. The results were in agreement with expression of MRP1 in six cases, and were discordant in four cases (1 MRP-/CAM+, 3 MRP+/CAM-). No correlation was observed between MRP1 expression and P-gp, lung resistance-associated protein (LRP) or CD34 expression, although there was a trend for more frequent MRP1 expression in P-gp-positive cases in MDS-AML (P = 0.08). Ten of the 26 patients treated with intensive chemotherapy achieved complete remission including six out of 16 MRP1+ and four out of ten MRP1- cases (P = NS). In conclusion, MRP1 expression was correlated with disease stage in MDS in our study. As for P-gp, discordant expression/function of MRP1 could be found in some cases, suggesting the existence of non-functional transport proteins in MDS. MRP1 expression did not seem to be a prognostic factor in MDS in our experience.

A B-cell mitogen from a pathogenic trypanosome is a eukaryotic proline racemase.

Lymphocyte polyclonal activation is a generalized mechanism of immune evasion among pathogens. In a mouse model of Trypanosoma cruzi infection (American trypanosomiasis), reduced levels of polyclonal lymphocyte responses correlate with resistance to infection and cardiopathy. We report here the characterization of a parasite protein with B-cell mitogenic properties in culture supernatants of infective forms, the cloning of the corresponding gene and the analysis of the biological properties of its product. We characterized the protein as a co-factor-independent proline racemase, and show that its expression as a cytoplasmic and/or membrane-associated protein is life-stage specific. Inhibition studies indicate that availability of the racemase active site is necessary for mitogenic activity. This is the first report to our knowledge of a eukaryotic amino acid racemase gene. Our findings have potential consequences for the development of new immune therapies and drug design against pathogens.

Lymphocyte polyclonal activation: a pitfall for vaccine design against infectious agents.

In this article, Bernardo Reina-San-Martin, Alain Cosson and Paola Minoprio summarize the marked alterations in the immune system functions after infection that might account for the poor success of effective parasite vaccine development. Many of the studies on oligoclonal B- and T-cell responses to parasite antigens aiming at vaccination strategies would seem to ignore more general, and perhaps fundamental, aspects of parasite-immune system interactions. In essence, because of its consequences on immunopathology and parasite escape, the authors ascribe a central importance in the pathogenesis of parasitic diseases to the 'nonspecific' polyclonal lymphocyte activation that occurs during infection. Hence, novel targets and strategies for immune intervention should be considered.