A new tool to investigate anorectal disorders in patients with multiple sclerosis: STAR-Q.

BACKGROUND: Bowel symptoms are commonly experienced by patients with Multiple sclerosis (PwMS), but no specific questionnaire validated in this population allows a rigorous assessment. OBJECTIVE: Validation of a multidimensional questionnaire assessing bowel disorders in PwMS. METHODS: A prospective, multicenter study was conducted between April 2020 and April 2021. The STAR-Q (Symptoms' assessmenT of AnoRectal dysfunction Questionnaire), was built in 3 steps. First, literature review and qualitative interviews were performed to create the first version, discussed with a panel of experts. Then, a pilot study assessed comprehension, acceptation and pertinence of items. Finally, the validation study was designed to measure content validity, internal consistency reliability (alpha coefficient of Cronbach) and test-retest reliability [intraclass correlation coefficient (ICC)]. The primary outcome was good psychometric properties with Cronbach's α>0.7 and ICC>0.7. RESULTS: We included 231 PwMS. Comprehension, acceptation and pertinence were good. STAR-Q showed a very good internal consistency reliability (Cronbach's α=0.84) and test-retest reliability (ICC=0.89). Final version of STAR-Q was composed of 3 domains corresponding in symptoms (Q1-Q14), treatment and constraints (Q15-Q18) and impact on quality of life (Q19). Three categories of severity were determined (STAR-Q≤16: minor, between 17 and 20: moderate, and≥21: severe). CONCLUSIONS: STAR-Q presents very good psychometric properties and allows a multidimensional assessment of bowel disorders in PwMS.

[Guidelines on the urological management of the adult patient with spinal dysraphism (spina bifida)]. / Recommandations sur la gestion du risque et la prise en charge urologique du patient adulte atteint de dysraphisme spinal (spina bifida).

INTRODUCTION: Improved life expectancy and prenatal screening have changed the demographics of spina bifida (spinal dysraphism) which has presently become a disease of adulthood. Urinary disorders affect almost all patients with spinal dysraphism and are still the leading cause of mortality in these patients. The aim of this work was to establish recommendations for urological management that take into account the specificities of the spina bifida population. MATERIALS AND METHODS: National Diagnosis and Management Guidelines (PNDS) were drafted within the framework of the French Rare Diseases Plan at the initiative of the Centre de Référence Maladies Rares Spina Bifida - Dysraphismes of Rennes University Hospital. It is a collaborative work involving experts from different specialties, mainly urologists and rehabilitation physicians. We conducted a systematic search of the literature in French and English in the various fields covered by these recommendations in the MEDLINE database. In accordance with the methodology recommended by the authorities (Guide_methodologique_pnds.pdf, 2006), proposed recommendations were drafted on the basis of this literature review and then submitted to a review group until a consensus was reached. RESULTS: Bladder dysfunctions induced by spinal dysraphism are multiple and varied and evolve over time. Management must be individually adapted and take into account all the patient's problems, and is therefore necessarily multi-disciplinary. Self-catheterisation is the appropriate micturition method for more than half of the patients and must sometimes be combined with treatments aimed at suppressing any neurogenic detrusor overactivity (NDO) or compliance alteration (anticholinergics, intra-detrusor botulinum toxin). Resort to surgery is sometimes necessary either after failure of non-invasive treatments (e.g. bladder augmentation in case of NDO resistant to pharmacological treatment), or as a first line treatment in the absence of other non-invasive alternatives (e.g. aponeurotic suburethral tape or artificial urinary sphincter for sphincter insufficiency; urinary diversion by ileal conduit if self-catheterisation is impossible). CONCLUSION: Spinal dysraphism is a complex pathology with multiple neurological, orthopedic, gastrointestinal and urological involvement. The management of bladder and bowel dysfunctions must continue throughout the life of these patients and must be integrated into a multidisciplinary context.

[Results and compliance of transcutaneous tibial nerve stimulation on overactive bladder syndrome in patients with Parkinson's disease. Retrospective Study.] / Résultats et observance de la stimulation transcutanée du nerf tibial dans l'hyperactivité vésicale de la maladie de Parkinson idiopathique. Étude rétrospective.

PURPOSE: To investigate efficiency and tolerance of transcutaneous tibial nerve stimulation (TNS) in the overactive bladder syndrome in patients with Parkinson's disease (PD), and to identify predictive factors for compliance. METHODS: We conducted a retrospective monocentric study with a cohort of 17 patients with PD who have used TNS for an overactive bladder syndrome. The efficiency of the treatment was evaluated on the clinical improvement felt (rated out of ten). Patients were classified as « adopters ¼ if they continued using TNS for at least one year after beginning the treatment or as « non adopters ¼ if they stopped. Patients characteristics were evaluated for their predictive value for compliance with TNS. RESULTS: Out of 17 patients, there were 9 women and 8 men, median age 66 years (55-77), median history for Parkinson's disease 8 years (1-22) and for urinary symptoms 3 years (1-10). Subjective efficiency was seen in 10 patients (59%), on nocturia and/or urinary incontinence for 9 patients (mean efficiency 5.75/10 and median efficiency 6.5/10). Three patients found TNS not effective, and four patients didn't use it long enough to evaluate. Two patients had side effects and stopped the TNS (feeling of electricity and restless leg syndrome). 7 patients were classified as « adopters ¼ and 10 patients as « non adopters ¼ after one year. Most evaluated characteristics proved not to be of predictive value for compliance with TNS except nocturia and pollakiuria (P=0.03 and P=0.05). CONCLUSION: Our study seems to reveal TNS is particularly effective on nocturia and urge. Moreover, nocturia and pollakiuria appear to be predictive factors for SNT compliance. Nocturia could be a prominent symptom in SNT's prescription. But studies with more patients should be conducted for obtain better patient selection in TNS. LEVEL OF EVIDENCE: IV.

[Is there any obstruction other than prostatic obstruction in Idiopathic Parkinson's Disease?] / Existe-t-il une obstruction autre que prostatique dans la Maladie de Parkinson Idiopathique ?

OBJECTIVE: To highlight the existence of pseudo-dyssynergia in Idiopathic Parkinson's Disease (IPD) constituting a functional bladder outlet obstruction. MATERIALS AND METHODS: A retrospective study was conducted by including men with a confirmed diagnose of IPD who participated in the SIROCCO rehabilitation program. Patients included clinically exhibited overactive bladder and voiding dysfunction without prostatic hypertrophy ultrasounded. They have been clinically assessed by the Urinary Symptoms Profile (USP) urinary symptom score. Bladder outlet obstruction was assessed by the pressure-flow study. Urodynamic obstruction has been quantified by the bladder obstruction index which depends on detrusor pressure at maximum flow rate and maximum flow rate. It has been defined by a BOOI>40. RESULTS: The pressure-flow profile was analyzed in 5 patients who met the inclusion criteria. In this group of 5 patients with IPD, the diagnosis was made on average 10.6 years (7-14) before the pressure-flow studies were performed. Our results objectified 4 patients obstructive among 5 and one equivocal patient. A striated pseudo-dyssynergia was found in the 3 obstructive patients and associated with a smooth pseudodyssynergia in one patient. CONCLUSION: We have observed, in this short series, a pseudo-dyssynergia by subjects suffering from IPD. LEVEL OF EVIDENCE: 3.

[Impact of pharmaceutical interventions on antibiotic therapy of urinary tract infections in rehabilitation center]. / Impact des interventions pharmaceutiques sur l'antibiothérapie des infections urinaires en service de soins de suite et de réadaptation.

BACKGROUND: The aim of this study was to assess the impact of medico-pharmaceutical partnership on the quality of antibiotic treatment in urinary tract infection (UTI) within rehabilitation center. MATERIAL: All antibiotic prescriptions were validated by the pharmacist at the start of treatment and twice a week. All patients with symptomatic urinary tract infection between January 1, 2014 to December 31, 2015 were included in this study. Addition to awareness among specifiers to promoting the appropriate use of antibiotics, the pharmacist suggested pharmaceutical interventions (PI) in order to improve the quality of antibiotic treatments. At the same time, 3 quality indicators (QI) were followed: duration, dosage, antibiotic susceptibility. The compliance rates of this 3 QI allowed to assess the quality of the antibiotic treatment in urinary tract infection. RESULTS: The study population included 154 patients corresponding to 252 UTI. Sixty-eight PI were made by pharmacist about urinary tract infection treatment (overdosage or under-dosing, duration unknown, inadequate route of administration). These QI achieved 96.4% compliance with duration, 98.8% compliance with dosage and 99.2% with the antibiotic susceptibility. CONCLUSION: This study allowed showing the medico-pharmaceutical impact on the quality of antibiotic treatments in UTI. The awareness among specifiers with a daily validation of prescription by the pharmacist allowed to improve urinary tract infections care in rehabilitation center. LEVEL OF EVIDENCE: 4.

[Seniority of neurobladder and effectiveness of a first intradetrusor injection of botulinum toxin]. / Ancienneté de la neurovessie et efficacité d'une première injection de toxine botulique intradétrusorienne.

UNLABELLED: Intradetrusor injection of botulinum toxin is one of the second-line therapy of neurologenic detrusor overactivity. GOAL OF THE STUDY: In 26% to 66% of the cases, intradetrusor injection of botulinum toxin is inefficient in order to reduce overactive bladder symptoms and/or overactive detrusor. The objective of this study is to determine whether it exists a link between the efficacy of the first IDBT and the length of neurological detrusor overactivity symptoms. METHODS: Retrospective study on 79 patients which have a first intradetrusor injection of botulinum toxin between January 2001 and December 2013. Inclusion criteria were patients older than 18 and having neurological detrusor overactivity. RESULTS: There is no significant difference of intradetrusor injection of botulinum toxin efficacy according to duration of urinary symptoms in the general neurologigal population (multiple sclerosis, spinal cord injury, spinal cord compression, ischemic pathology, infectious pathology) with the mean age being 46 years. On the contrary, the length of evolution of neurological detrusor overactivity symptoms before the intradetrusor botox injection therapy and the efficiency of the first intradetrusor injection of botulinum toxin seem to be correlated with negative results in patients with multiple sclerosis. CONCLUSIONS: The duration of urinary symptoms is a predictive factor of primary failure of intradetrusor injection of botulinum toxin in multiple sclerosis patients, in univariate analysis.

[Lazy bladder syndrome: review of 126 cases]. / Mégavessie congénitale: analyse clinique et urodynamique de 126 cas.

PURPOSE: The lazy bladder syndrome (LBS) is characterized by an infrequent voiding, a large bladder capacity without neurological or urological disorders. In spite of being relatively common, there is little literature about it. The aim of our study was to compare the clinical features and urodynamic findings in asymptomatic or symptomatic patients with lazy bladder syndrome. PATIENTS AND METHODS: We reviewed the charts of 126 adult patients diagnosed with lazy bladder syndrome. Clinical and radiological features, urodynamic findings and therapeutic management were evaluated. With these data, we divided patients into 2 groups: asymptomatic and symptomatic patients. After, we performed a comparative analysis of the data. RESULTS: The incident of LBS was significantly higher in women (81%). Twenty-one patients were asymptomatic (17%), 105 patients were symptomatic (83%). The patients with symptomatic LBS were significantly older (54.3 years ± 14.7). Voiding dysfunction (53%) and urinary retention (27%) were the most common symptoms in symptomatic group. In the uroflowmetry test, maximum and mean uroflow were significantly higher in asymptomatic group (P=0.0074). Reduced bladder sensation revealed no difference in the 2 groups, but in the symptomatic group, detrusor has also a poor contractility (P=0.0001). Nineteen patients (18%) had uro-nephrological complications. CONCLUSION: LBS is certainly underestimated. Voiding dysfunction, urinary retention in infrequent voiders or uro-nephrological complication (urinary tract infection with fever, ureteral reflux…) should recall LBS diagnosis. The hypothesis of bladder structural failure or autonomic nervous system dysfunction may be discussed (suggested). LEVEL OF EVIDENCE: 5.

[Bacterial ecology and resistance to antibiotics in patients with neurogenic overactive bladder treated with intravesical botulinum toxin injections]. / Écologie bactérienne et profils de résistance aux antibiotiques chez les patients avec hyperactivité du détrusor d'origine neurologique, traités par injections de toxine botulique intradétrusoriennes.

INTRODUCTION: For the last ten years, botulinum neurotoxin type A has become the gold standard for the treatment of neurogenic overactive detrusor. Bacterial colonization is common for these patients using clean intermittent self-catheterization, and toxin injections are at risk of urinary tract infections. OBJECTIVES: The aim of our study was to determine the prevalence of different germs and their resistance to antibiotics in patients with neurogenic bladder, treated with intravesical botulinum toxin injections. MATERIAL AND METHOD: This epidemiologic study took place from September to October 2012 in a urodynamic and neurourology unit in a teaching hospital in Paris, France. RESULTS: Eighty patients with a valid urine culture according to our protocol, were included. Fourty-four culture were positive with 45 bacteria. We found an Escherichia coli in 42.5%, a Klebsiella pneumoniae in 7.5%, a Citrobacter freundii and an enterococcus in 2.5%, and a Staphylococcus aureus in 1.25%. Penicillin resistance were found in 51.11%, 3rd generation cephalosporins in 8.89%, quinolones in 28.89% and sulfamids in 24.44%. None were resistant to fosfomycin. CONCLUSION: E. coli was the most frequent bacterium. No resistance to fosfomycin was found.

[Urethral meatus deformities and urethra hypospadias in women: prevalence, problems and definitions. Study of 12,739 patients]. / Méat urétral enfoui et urètre hypospade chez la femme : prévalence, problématiques et définitions. Étude sur 12 739 patientes.

UNLABELLED: The difficulty to access to the urethral meatus is found in women in relation to morphological abnormalities of urogenital or ectopic locations meatus, whether acquired (urethral meatus buried [UMB]) or congenital reality (urethra hypospadias [UH]). The pathophysiology is not unequivocal with lack of clear and specific studies. PURPOSE: Verify the existence of specific functional problems, assess the prevalence and identify the anatomical features of UMB and UH. MATERIALS: UMB and UH were sought in a computerized database listing the patients attending a neurourology department between 2000 and 2014 for a pelvic-perineal disease. Each case was analysed for specific reached leaks, urinary tract infections and difficulties catheterization. RESULTS: Of the 12,739, 131 patients (1%) met the inclusion criteria, including 18 UH and 113 UMB. Ninety-one patients consulted for urinary disorders of neurological origin. The circumstances of UMB and UH discovery were: perineal systematic review in 63 cases (48%); difficulties of urethral catheterization in 65 cases (49%); urinary incontinence for 3 patients (3%). Urinary tract infections have not led to the discovery of UMB or UH. Difficulties locating the urethral meatus were congenital (UH) in 18 cases (13%). In 113 cases (87%), it was an acquired abnormality (UMB) overweight for 16 patients (12%), troublesome spasticity of the adductor muscles in 18 cases (14%), vulvovaginal atrophy in 5 cases (4%) and a patient (1%) with a pelvic organ prolapse. No details were given for the remaining 72 patients (54%). CONCLUSION: The urethral meatus difficult access due to MUE or UH can be met in a specialized service but the exact concept of MUE be defined. It can be considered as urethral meatus difficult to access and the cause is acquired. Functional impairment may be particularly important in patients requiring catheterization for bladder emptying. LEVEL OF EVIDENCE: 4.

[Comparison between autonomic nervous system cardiovascular tests (ANSCVT) and lacrymal and or salivary secretion tests (LSST) in overactive bladder syndrome and voiding dysfunction]. / Apport des tests sécrétoires dans la mise en évidence d'une dysrégulation végétative au cours des troubles vésicosphinctériens idiopathiques. Comparaison avec les tests cardiovasculaires de la fonction autonome.

PURPOSE: To compare autonomic nervous system cardiovascular tests (ANSCVT) and lacrymal and or salivary secretion tests (LSST). METHOD: One hundred and twenty-four patients (57 females, 67 males, mean age 45) with lower urinary tract symptoms (overactive bladder syndrome or voiding dysfunction) without neurogenic or urological causes, were included. Urodynamic was performed in all the patients with LSST (saliva flowmetry-sialometry [SFS], candy weight-loss test [CWT], Schirmer test [SchT]) and ANSCVT (ratio 30:15, orthostatic hypotension analysis, deep breath test [DBT], Valsalva maneuver [VM], cold pressor test [CPT] and hand grip test [HGT]). RESULTS: In eight cases, ANSCVT were altered (four in OAB syndrome, four in voiding dysfunction). No correlation was found between positive ANSCVT and LSST (P=0.72 for CWT, P=1 for SFS, P=0.1 for SchT). In contrary, there is a significant correlation between SchT and CWT (P=0.049), but not between SchT and SFS (P=0.69) or SFS vs CWT (P=0.06). CONCLUSION: In this series LSST were not sufficient to track down autonomic nervous system alterations and ANSCVT always necessary. Autonomic dysfunctions were infrequent in OAB syndrome and "idiopathic" voiding dysfunctions (6.5%).

[Self intermittent catheterization and voiding duration: in vitro flow rate assessment of catheters used in self-catheterization]. / Autosondages urinaires et temps de vidange : étude expérimentale de la vitesse de drainage des différentes sondes d'autocathétérisme.

OBJECTIVE: To assess the flow rate obtained by catheters used in self intermittent catheterization. MATERIAL: In vitro comparative study designed to compare the average flow rate obtained by intravesical catheters, by repeated flowmetric measures. The catheters studied were the most used in France in Fr10, 12 and 14 for female catheters and in Fr12, 14 and 16 for male catheters. RESULTS: We observed a strict relationship between Charriere and flow rate, both in female and male catheters These results were statistically significant (P<0.05). For female catheters, the average flow rate varied from 2.83 to 3.7 mL/s for Fr10 catheters, from 4.31 to 5.35 mL/s for Fr12 catheters and from 7.00 to 7.85 mL/s for Fr14 catheters (P<0.05). For male catheters, the average flow rate varied from 4.53 to 5.00 mL/s for Fr12 catheters, from 6.95 to 8.17 mL/s for Fr14 catheters and from 10.4 to 11.07 mL/s for Fr16 catheters (P<0.05). In female and male population, despite the observed flow rate differences between catheters, there were no statistically significant differences. CONCLUSION: This study demonstrated a better flow rate when Charriere increases. Thus, an objective adaptation of self catheterization's materiel is possible when the patient wishes to improve flow rate in order to reduce self intermittent catheterization duration.

Do children and adolescents with type 1 diabetes suffer from a lack of resources in France? Results from a benchmark study in the New Aquitaine region.

BACKGROUND: A benchmark study was conducted in the southwest of France, in the New Aquitaine region, to investigate metabolic outcomes and availability of resources in pediatric diabetes units. We assessed whether the level of care was in accordance with the International Society for Pediatric and Adolescent Diabetes recommendations. METHODS: Demographic and clinical data were collected, as were all HbA1c tests for the 2017 calendar year. Pediatricians specialized in diabetes care were invited to complete an online survey concerning means allocated to the management of type 1 diabetes in their centers. RESULTS: Sixteen centers provided data for 1277 patients and 3873 clinical visits. A total of 1115 children suffering from diabetes for more than 1 year were studied. Median HbA1c was 8% (7.4-8.6) for the whole region. Only 29.2% of children had good metabolic control in accordance with the <7.5% target. We identified slight but significant variation in glycemic control among centers (P=0.029). The use of an insulin pump varied greatly among centers but did not explain HbA1c differences. We did not identify a correlation between medical or paramedical time dedicated to the follow-up of diabetic patients and the mean HbA1c of each center. For 100 diabetic patients, follow-up was provided by 0.42 physicians (0.23-1.50), 0.15 nurses (0-0.56), 0.12 dietitians (0-0.48), and 0.07 psychologists (0-0.30). CONCLUSION: This study demonstrates a lack of human resources allocated to the management of type 1 diabetes in the region that is far below international recommendations. The proportion of children achieving the international glycemic target is low. There is a clear need to improve glycemic control in children, which will only be possible with improved professional practices, encouraged by benchmark studies, and by increasing the size of our multidisciplinary teams.

Proteomic characterisation of leech microglia extracellular vesicles (EVs): comparison between differential ultracentrifugation and Optiprep™ density gradient isolation.

In Mammals, microglial cells are considered as the resident immune cells in central nervous system (CNS). Many studies demonstrated that, after injury, these cells are activated and recruited at the lesion site. Leech microglia present a similar pattern of microglial activation and migration upon experimental lesion of CNS. This activation is associated with the release of a large amount of extracellular vesicles (EVs). We collected EVs released by microglia primary culture and compared two different protocols of isolation: one with differential ultracentrifugation (UC) and one using an additional Optiprep™ Density Gradient (ODG) ultracentrifugation. Nanoparticles tracking analysis (NTA) and transmission electron microscopy (TEM) were used to assess vesicles size and morphology. The protein content of isolated EVs was assessed by mass spectrometry approaches. Results showed the presence of EV-specific proteins in both procedures. The extensive proteomic analysis of each single ODG fractions confirmed the efficiency of this protocol in limiting the presence of co-isolated proteins aggregates and other membranous particles during vesicles isolation. The present study permitted for the first time the characterisation of microglial EV protein content in an annelid model. Interestingly, an important amount of proteins found in leech vesicles was previously described in EV-specific databases. Finally, purified EVs were assessed for neurotrophic activity and promote neurites outgrowth on primary cultured neurons.

[Maternal-fetal staphylococcal toxic shock syndrome with chorioamniotitis]. / Choc toxique staphylococcique maternofoetal sur chorioamniotite.

We report a rare case of mother-infant pair with Staphylococcal Toxic Shock Syndrome (TSS). A term neonate was born by caesarean section for maternal septic syndrome during per-partum. He presented with respiratory distress complicated by pulmonary hypertension, skin rash, and multiple organ system involvement. Staphylococcus aureus was isolated from placenta, surface swabs and gastric aspirate. He received adapted antibiotics, respiratory support by high frequency ventilation and NO. The mother had shock, skin rash and inflammatory syndrome. Outcome was good in both cases. The isolate produced enterotoxin C and L. Shock, exanthematous disease and multi-organ involvement complicating a staphylococcal infection in neonate must lead to suspect a TSS.

Phosphonoacetaldehyde hydrolase from Pseudomonas aeruginosa: purification properties and comparison with Bacillus cereus enzyme.

Phosphonoacetaldehyde hydrolase (2-oxoethylphosphonate phosphonohydrolase, EC 3.11.1.1) has been purified to electrophoretic homogeneity from cells of Pseudomonas aeruginosa A 237 grown in a culture medium containing 2-aminoethylphosphonate as both phosphorus and carbon sources. The native Mr has been estimated to be 62,000 +/- 2000, using a gel filtration column equilibrated with standard proteins. A subunit of Mr 30,000 +/- 1000 determined in sodium dodecyl sulfate-polyacrylamide gel electrophoresis gives evidence of a homodimeric structure. The enzyme, which catalyzes the C-P bond cleavage of phosphonoacetaldehyde, has a Km value of 210 microM. It is moderately inhibited by methyl-, ethyl-, propyl- and butylphosphonic acids and activated by aminomethyl-, aminoethylphosphonic acids as well as by phosphonoformic, phosphonoacetic and phosphonopropionic acids. Inhibition by orthophosphite is a time-dependent process which exhibits first-order kinetics and is enhanced by the presence of acetaldehyde. Assays for phosphite removal by dilution or dialysis do not reverse the inhibition. Phosphonoacetaldehyde hydrolase inactivation by phosphite ion appears to be inconsistent with the concept of a Schiff base intermediate as proposed for Bacillus cereus enzyme.

[2-Amino-ethylphosphonic acid transport in Pseudomonas aeruginosa]. / Transport de l'acide amino-2-éthylphosphonique chez Pseudomonas aeruginosa

2-Aminoethylphosphonic acid (ciliatine) can be used as a source of phosphorus or nitrogen by Pseudomonas aeruginosa. The conditions of its uptake have been investigated. The transport is inducible by ciliatine itself or by its homologue, 3-aminopropylphosphonate, but neither by other phosphonic compounds nor by carboxylic or sulfonic related derivatives. The induction was not suppressed by inorganic phosphate. The transport appears to be an active process, pH and temperature dependent: it requires energy and is dependent on new protein synthesis. The uptake follows Michaelis kinetics. The substrate specificity involved in ciliatine uptake favours the existence of two different transport systems: the first one, inducible by ciliatine, was very sensitive towards different aminophosphonic acids and was competitively inhibited by inorganic phosphate and methylphosphonate; the second transport system, inducible by 3-amino-propylphosphonate, appeared less sensitive towards alpha-aminophosphonic acids and was non competitively inhibited by phosphate and methylphosphonate. No interactions were observed with related aminocarboxylic acids or with taurine. Some molecular structural requirements for the binding of an effector on both permeases are discussed. The regulatory function of inorganic phosphate, the chief breakdown product of ciliatine, is also emphasized.

In vivo incorporation of cytidine-monophosphate-ciliatine into rat liver lipids.

1. In vivo this investigation was carried out in order to compare the incorporation into rat lipids of free [1,2-minus 14C]-ciliatine and CMP-[1,2-minus 14C]-ciliatine which is the precursor in phosphonolipid biosynthesis. 2. The incorporation of the radioactivity from CMP-[1,2-minus 14C]-ciliatine took place more rapidly than that from free [1,2-minus 14C]-ciliatine in both liver and kidney. The amount of radioactivity from the CMP-[1,2-minus 14C]-ciliatine incorporated into total liver lipids was about 5 times higher than that incorporated into total liver lipids of rat two hrs after injecting free-[1,2-minus 14C]-ciliatine. 3. The amount of [1,2-minus 14C]-ciliatine incorporated into total liver lipids was 15 and 21 times higher than that incorporated into total kidney lipids of rat two and four hrs after injecting free [1,2-minus 14C]-ciliatine. 4. If the main pathway for the phosphonolipid biosynthesis is via CMP-ciliatine, the rate of phosphonolipid formation from CMP-ciliatine must therefore be higher than that from free-ciliatine. The results obtained here indicate therefore that the main pathway for phosphonolipid biosynthesis is a pathway involving CMP-ciliatine. 5. An unknow compound was detected in the water soluble fraction of the acid hydrolyzate of liver phosphonolipids. This material migrated with the N-trimethyl-derivative of ciliatine on the thin-layer chromatogram. The result shows that there is therefore a possibility of methylation of exogenous ciliatine to the phosphonate analogue of choline in the mammalian body.

(beta-Chloro-alpha-aminoethyl)phosphonic acids as inhibitors of alanine racemase and D-alanine:D-alanine ligase.

The (beta-chloro-, (beta, beta-dichloro-, and (beta, beta, beta-trichloro-alpha-aminoethyl)phosphonic acids have been synthesized and their inhibitory properties on the alanine racemases [EC 5.1.1.1] and the D-Ala:D-Ala ligases [EC 6.3.2.4] from Pseudomonas aeruginosa and Streptococcus faecalis have been evaluated. The monochloro and the dichloro derivatives of Ala-P exhibit a strong inhibition on the racemases of the two species tested but do not behave as suicide substrates. Only the D-Ala:D-Ala ligase of S. faecalis is inhibited by these compounds. The poor antibacterial activity observed with beta-chloro- and beta, beta-dichloro-Ala-P might be enhanced by the peptide-transport strategy.

(1-Amino-2-propenyl) phosphonic acid, an inhibitor of alanine racemase and D-alanine:D-alanine ligase.

DL-(1-Amino-2-propenyl)phosphonic acid was synthesized through the sequential oxidation, sulfoxide elimination, and deprotection of diphenyl [1-[(benzyloxycarbonyl)amino]-3-(phenylthio)propyl] phosphonate. This analogue of vinylglycine is a strong inhibitor of the alanine racemases from Pseudomonas aeruginosa and Streptococcus faecalis and of the D-Ala:D-Ala ligase from this latter species. This molecule is ineffective against the whole bacterial cells. Unlike vinylglycine, this unsaturated phosphonate does not inhibit the following mammalian enzymes: aspartate aminotransferase, alanine aminotransferase, D-amino acid oxidase, which indicates its specificity. Thus, its incorporation in a peptide structure could induce interesting antimicrobial properties.