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The neurogenic bladder in spinal cord injury--pattern and management.

This study describes the various types of neurogenic bladder in spinal cord injury in relation to the level of lesion, defines the aims of bladder management, and discusses the importance of highly individualised management strategies and long-term follow-up. Urodynamic studies were done on 47 new patients with traumatic spinal cord injury when they had return of reflexic bladder activity. This study was conducted over a one-year period. Fifty-five per cent (n = 26) sustained cervical injuries (38.5% complete, 61.5% incomplete), 12.8% (n = 6) had thoracic injuries, 29.8% (n = 14) had lumbar injuries, and 2.1% (n = 1) had sacral injury. The urodynamic patterns according to injury level are shown in Table I. In patients with complete cervical injuries, 80% had detrusor sphincter dyssynergia (DSD), and areflexia was seen in 20% (n = 2). Of those with incomplete cervical injury, 7 (43.8%) had DSD, 5 (31.3%) had detrusor hyperrflexia without DSD, and 2 (12.5%) had areflexia or hyporeflexia. Normal urodynamic studies were only found in patients with incomplete cervical injury (n = 2). Of the 6 patients with thoracic injury, 4 (66.6%) had detrusor areflexia and 2 had DSD. The 2 patients with DSD had injury levels at T4/T6 and T5 respectively. Eleven (78.6%) patients with lumbar injury had detrusor areflexia, one (7.1%) had detrusor hyperreflexia (without DSD), and 2 (14.3%) had a normal urodynamic study. The various patterns of bladder management are shown in Table II. In total, there were 17 patients with DSD. Of these, 9 (52.9%) elected for intermittent catheterisation together with pharmacological therapy, 5 (29.4%) passed urine via spontaneous voiding/tapping, one (5.9%) had an in-dwelling catheter by virtue of his lack of manual dexterity and no care-giver, and 2 (11.8%) patients opted for sacral anterior root stimulator (SARS) or the Brindley device. Of the 6 patients with detrusor hyperreflexia, 4 (66.7%) passed urine spontaneously and 2 (33.3%) patients choose intermittent catheterisation together with pharmacologic therapy. There were 20 patients with detrusor areflexia/hyporeflexia; 15 (75%) were on clean intermittent catheterisation, 4 (20%) voided via straining and 1 (5%) had a suprapubic catheter inserted. The re-discovery of intermittent self-catheterisation, improved medical care, bladder training and surgical advances have enabled the goals of bladder management to be realised; namely safe bladder pressures, low residual urine volume and the attainment of continence.

Adolescent↗

Augmentation of nitric oxide to treat detrusor-external sphincter dyssynergia in spinal cord injury.

Detrusor-external sphincter dyssynergia (DSD) is a common cause of bladder outlet obstruction in men with spinal cord injuries, which if left untreated leads ultimately to renal failure. External sphincterotomy is currently the main treatment for DSD. However, obstruction persists in a substantial proportion of cases after this procedure. There is no effective drug treatment for DSD. Nitric oxide is an inhibitory neurotransmitter synthesised by nitric oxide synthase. Both animal and human studies suggest that nitric oxide mediates urethral sphincter relaxation. Nitric-oxide-synthase staining neurons have been identified in very high density in the urethral sphincters of a variety of animals and in human beings. Relaxation of the urethral sphincter is abolished by inhibitors of nitric oxide synthase and enhanced by nitric oxide donors. Mice with targeted deletion of the gene, for neuronal nitric oxide have urethral sphincters that do not relax in response to electrical stimulation. We hypothesise that augmentation of external sphincter nitric oxide could be an effective pharmacological treatment for DSD. Currently available nitric oxide donors such as glyceryl trinitrate or isosorbide mononitrate could be used to deliver nitric oxide to the urethral sphincter. The variable pharmacokinetics of these drugs combined with different modes of delivery (sublingual, buccal, or oral) could be used to achieve both short-term and long-term increases in concentrations of sphincter nitric oxide, thereby resulting in either acute or chronic lowering of urethral pressure. The safety and efficacy of this potential treatment for DSD needs to be established in clinical trials of men with spinal cord injures with DSD.

Animals↗

Disturbances of micturition in patients with a spinal arteriovenous malformation.

Neuro-urological studies were performed on 9 patients with a spinal arteriovenous malformation (S-AVM). The micturitional history revealed that all 9 patients had voiding symptoms, obstructive in 9 and irritative in 3 patients. All patients still had obstructive symptoms after treatment of S-AVM. Six of the 9 patients had a large volume of residual urine before treatment; 5 showed urinary retention. Four of the 5 patients (80%) for whom urodynamic studies were performed before treatment had micturitional dysfunction; 2 patients had detrusor hyperreflexia, 1 with detrusor external urethral sphincter dyssynergia (DSD) and 1 with a normal sphincter, 1 patient had an autonomous bladder with DSD and 1 patient had an atonic bladder with DSD. Only 1 patient had a normal bladder and sphincter. Findings of the urodynamic studies after treatment in 9 patients showed detrusor hyperreflexia in 3 patients (2 with DSD and 1 with normal sphincter), autonomous bladder in 1 patient with DSD, atonic bladder in 4 patients (2 with DSD, 1 with incompetent sphincter and 1 with normal sphincter) and normal bladder with normal sphincter in 1 patient. Lower urinary function after treatment of S-AVM was improved in 2 patients, unchanged in 4 patients and worsened in 3 patients. The above results showed 80% of S-AVM had a severe neuropathic bladder manifested mainly by disturbance of micturition. Treatment of S-AVM does not necessarily improve the lower urinary tract function.

Adult↗

Oversulfated dermatan sulfate exhibits neurite outgrowth-promoting activity toward embryonic mouse hippocampal neurons: implications of dermatan sulfate in neuritogenesis in the brain.

Brain-specific chondroitin sulfate (CS) proteoglycan (PG) DSD-1-PG/6B4-PG/phosphacan isolated from neonatal mouse brains exhibits neurite outgrowth-promoting activity toward embryonic rat and mouse hippocampal neurons in vitro through the so-called DSD-1 epitope embedded in its glycosaminoglycan side chains. Oversulfated CS variants, CS-D from shark cartilage and CS-E from squid cartilage, also possess similar activities. We have proposed that the neuritogenic property of the DSD-1 epitope may be attributable to a distinct CS structure characterized by the disulfated D disaccharide unit [GlcUA(2S)-GalNAc(6S)]. In this study, we assessed neuritogenic potencies of various oversulfated dermatan sulfate (DS) preparations purified from hagfish notochord, the bodies of two kinds of ascidians and embryonic sea urchin, which are characterized by the predominant disulfated disaccharide units of [IdoUA-GalNAc(4S,6S)] (68%), [IdoUA(2S)-GalNAc(4S)] (66%) plus [IdoUA(2S)-GalNAc(6S)] (5%), [IdoUA(2S)-GalNAc (6S)] (>90%), and [IdoUA-GalNAc(4S,6S)] (74%), respectively. They exerted marked neurite outgrowth-promoting activities, resulting in distinct morphological features depending on the individual structural features. Such activities were not observed for a less sulfated DS preparation derived from porcine skin, which has a monosulfated disaccharide unit [IdoUA-Gal-NAc(4S)] as a predominant unit. The neurite outgrowth-promoting activities of these oversulfated DS preparations and DSD-1-PG were eliminated by the specific enzymatic cleavage of GalNAc-IdoUA linkages characteristic of DS using chondroitinase B. In addition, chemical analysis of the glycosaminoglycan side chains of DSD-1-PG revealed the DS-type structures. These observations suggest potential novel neurobiological functions of oversulfated DS structures and may reflect the physiological neuritogenesis during brain development by mammalian oversulfated DS structures exemplified by the DSD-1 epitope.

Animals↗

Delirium superimposed on dementia in a community-dwelling managed care population: a 3-year retrospective study of occurrence, costs, and utilization.

BACKGROUND: Dementia is a growing public health problem and a well-described risk factor for delirium. Yet little is known about delirium superimposed on dementia in community-dwelling populations. The purpose of this study was to examine the 3-year occurrence, healthcare utilization, and costs associated with delirium superimposed on dementia in community-dwelling persons. METHODS: We used a 3-year cross-sectional, retrospective design with an administrative database from a large managed care organization. Four individually matched samples of 699 individuals each were selected for comparison purposes: delirium superimposed on dementia (DSD), dementia alone, delirium alone, and a control group with neither delirium nor dementia. The occurrence rate of DSD was calculated by measuring those individuals with a dementia diagnosis that were also coded with an International Classification of Diseases, Ninth Edition Clinical Modification (ICD-9 CM) code for delirium or delirium with dementia. RESULTS: Of the total sample of 76,688 persons aged 65 years or older in the managed care organization, 7347 (10%) were coded as having dementia, and an additional 763 (1%) as having delirium alone. Among the 7347 with dementia, 976 (13%) had DSD, representing 1.3% of the total sample. After log transformation of total costs and adjustment for multiple covariates, the adjusted mean total health care costs remained significantly higher for the DSD group than for all other groups. CONCLUSIONS: This study is the first to report the occurrence rate of DSD in a community-dwelling population, and to demonstrate the substantial health care costs and utilization associated with DSD.

Aged↗

Comparison of the use of L-tyrosine apodecarboxylase and D-serine apodehydratase for plasma pyridoxal phosphate assay.

The enzymatic methods for plasma pyridoxal 5'-phosphate (PLP) assay using L-tyrosine apodecarboxylase (apo-LTD) and D-serine apodehydratase (apo-DSD) were compared with respect to their operating characteristics, accuracy and precision. With the apo-LTD assay, the recovery of authentic PLP added to irradiated plasma was 96-100% and the precision for within-run and run-to-run replicates was 4-5% (coefficient of variation). The recovery of authentic PLP with the apo-DSD assay tended to be lower (viz., 95%) and the within-run and run-to-run coefficients of variation tended to be higher (viz., 5-6%), but these differences were not statistically significant. When these two assay methods were directly compared in determining the plasma PLP levels of 67 hospitalized patients, the regression lines exhibited correlation coefficients of 0.89 and 0.92 and slopes of 0.77 and 0.78, respectively. When the plasma PLP values were less than 7.5 ng/ml, the values determined by the apo-DSD assay tended to be higher than those measured by the apo-LTD method and vice versa. The lack of better agreement between the two assay methods may be explained by the fact that an inhibitor exists in plasma extracts that impairs the binding of PLP to apo-DSD and that the correction for this interference may not be uniform from one plasma sample to another. However, if one is willing to tolerate the small discrepancies between the values obtained by the apo-DSD and apo-LTD assays, these assay methods can be used interchangeably. The apo-DSD assay has the advantage of being easily adapted to a modern automated spectrophotometric centrifugal analyzer.

Apoenzymes↗

Effects of neurogenic bladder dysfunction in utero seen in neonates with myelodysplasia.

Twenty neonates with myelodysplasia were prospectively evaluated during the first month of life with urodynamic studies, contrast voiding cystourethrograms (VCUG) and renal ultrasound scans. Ten of 20 infants had abnormal VCUGs--6 with vesicoureteric reflux (VUR) and 4 with bladder trabeculation alone. Only 2/20 neonates had abnormal ultrasounds--both with hydroureteronephrosis secondary to VUR. Elevated leak point pressure (LPP) and/or detrusor sphincter dyssynergia (DSD) were present in 10/20 infants--6 with elevated LPP and DSD, 3 with elevated LPP alone and 1 with DSD alone. Eight of 10 neonates with DSD or elevated LPP had abnormal VCUGs--4 with VUR and 4 with bladder trabeculation alone. Conversely, 8/10 neonates without DSD or elevated LPP had normal VCUGs. Contrast VCUG performed shortly after birth, therefore, is essential for the discovery of bladder trabeculation and reflux. There is a strong correlation between an abnormal VCUG and the presence of DSD and elevated LPP, suggesting that neurogenic bladder dysfunction in utero can lead to these structural abnormalities.

Abnormalities, Multiple↗

Acaricidal properties of Artemisia absinthium and Tanacetum vulgare (Asteraceae) essential oils obtained by three methods of extraction.

Essential oils of Artemisia absinthium L. and Tanacetum vulgare L. were extracted by three methods, a microwave assisted process (MAP), distillation in water (DW) and direct steam distillation (DSD), and tested for their relative toxicity as contact acaricides to the two spotted spider mite, Tetranychus urticae Koch. All three extracts of A. absinthium and of T. vulgare were lethal to the spider mite but to variable degrees. The LC50 obtained from the DSD oil of A. absinthium was significantly lower (0.04 mg/cm2) than that of the MAP (0.13 mg/cm2) and DW (0.13 mg/cm2) oil of this plant species. DSD and DW extracts of T. vulgare were more toxic (75.6 and 60.4% mite mortality, respectively, at 4% concentration) to the spider mite than the MAP extract (16.7% mite mortality at 4% concentration). Chromatographic analysis indicated differences in composition between the more toxic DSD oil of A. absinthium and the other two extracts of this plant, indicating that a sesquiterpene (C15H24) compound present in the DSD oil and absent in the other two may enhance the toxicity of the DSD oil. Chemical analysis of the T. vulgare extracts indicated that beta-thujone is by far the major compound of the oil (>87.6%) and probably contributes significantly to the acaricidal activity of the oil.

Animals↗

[Electromyographic study on the external urethral sphincter of the male--power spectrum analysis with fast Fourier transformation].

In 23 male patients, the electrical activity of external urethral sphincter muscle was sampled before examination of cystometry (Rest), at first desire to void (FDV), maximum desire to void (MDV) and during urination (Void) by means of electromyography (EMG). Sampling time of each event was 2400 msec. The electrical activity was amplified with a lower limiting frequency of 20 Hz and an upper limiting frequency of 10000 Hz, and recorded on magneto-optical desk. Spectra were obtained using a Hamming window. The action potential of the muscle was quantitatively analyzed and power spectrum of the needle EMGs were analyzed from the magneto-optical disk by a spectrum analyzer using fast Fourier transformation (FFT, Sande-Tukey method). From each power spectrum, mean power frequency (MPF) was obtained from a calculator connected to the spectrum analyzer. Twenty three patients were divided into three groups as follows: 8 patients without any neurological abnormality (normal group), 7 patients with neurogenic bladder showing detrusor-sphincter-dyssynergia (DSD+ group) and 8 patients with neurogenic bladder without detrusor-sphincter-dyssynergia (DSD- group). The results obtained were as follows: 1) The motor unit potentials at Rest had the mean amplitude of 210 +/- 59.4 microV, 329.3 +/- 157.1 microV and 177.6 +/- 132.8 microV in normal group, DSD+ group and DSD- group, respectively. The mean duration were 4.3 +/- 0.2 msec, 5.9 +/- 1.9 msec, and 7.3 +/- 4.5 msec., respectively. The mean phases were 2.8 +/- 0.6, 2.8 +/- 0.5 and 2.5 +/- 0.3, respectively. Statistically there was no difference in amplitude, duration and phase among three groups. 2) In normal group, the power over than -20 dB was distributed from 150 to 220 Hz windows at Rest and FDV. The needle EMGs at MDV showed interference pattern and the power increased over -20 dB in all windows. The power of high frequency area relatively increased. The action potential of the muscle disappeared during urination and the power also disappeared. The average MPF was 103 Hz, 102 Hz, 150 Hz and 98 Hz at Rest, FDV, MDV and Void, respectively. 3) In DSD+ group, the needle EMGs showed interference pattern in MDV and Void, and the power increased only in low frequency area. The average MPF was 104 Hz, 105 Hz, 114 Hz and 120 Hz at Rest, FDV, MDV and Void, respectively. 4) Because of damage to nerves, the action potential of the muscle was difficult to obtain from 3 patients of DSD- group, and the power was not demonstrated.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Dural ectasia in children with Marfan syndrome: a prospective, multicenter, patient-control study.

UNLABELLED: The clinical diagnosis of Marfan syndrome in childhood is difficult, because symptoms may not have developed to their full expression until adulthood. The Ghent nosology for the diagnosis of Marfan syndrome classifies dural ectasia as a major diagnostic criterion. More than two thirds of adult patients with Marfan syndrome show dural ectasia, while the frequency in childhood is unknown. This prospective multicenter observational patient-control study was performed to identify pathologic changes of the lumbosacral spine in young patients with Marfan syndrome. DESIGN: Prospective clinical trial, multicentric, cross-sectional. SETTING: MRI of the lumbosacral spine. PATIENTS: Twenty patients with proven Marfan syndrome, 20 patients suspicious for Marfan syndrome and 38 healthy controls. OUTCOME MEASURES: Vertebral body diameter (VBD) from L1 to S1, dural sac diameter (DSD) from L1 to S1, dural sac ratio (DSR), qualitative assessment of the lumbosacral spine. RESULTS: DSD and VBD in different age groups were higher in patients with proven or suspected Marfan syndrome than in healthy controls (DSD: L1, 6-8 years, P < 0.05). VBD related to body height showed a similar growth related increase in patients with proven or suspected Marfan syndrome and controls. DSD related to body height was elevated in patients with proven or suspected Marfan syndrome at different levels of the lumbar spine. DSD at levels L1, L5, and S1, and DSR at levels L5 and S1 of patients with proven Marfan syndrome were significantly higher (P < 0.05) than in controls. CONCLUSION: Even during childhood pathologic changes inside the lumbosacral spine of patients with Marfan syndrome can be observed. Dural ectasia, which occurs at different levels of the lumbar spine, can be detected at levels L5 and S1 in up to 40% of patients with Marfan syndrome.

Adolescent↗

Effects of repeated sleep deprivation in the dark- or light-period on sleep in rats.

This study was designed to examine the differences between sleep duration and EEG when sleep was restricted to the rest- or activity-phase for 5 successive days, achieved by repeated sleep deprivation in the dark (DSD) or light-period (LSD). In the DSD-experiment the percentages of the vigilance states were comparable to the level of the baseline light period. In LSD, the amounts of all sleep states increased substantially relative to baseline dark. The sleep episodes were lengthened in DSD and LSD. The duration of NREM-sleep and the sleep episodes remained longer in the light than in the dark, indicating circadian influences. In the first hours after sleep deprivation the delta activity during NREM-sleep was enhanced in LSD and to a lesser extent in DSD. This effect diminished over the consecutive days in both experiments. The EEG energy gained during sleep and its accumulation pattern on each day in DSD and LSD were strikingly similar, thereby reflecting a homeostatic process. After the sleep deprivation days, small changes were observed in the distribution of the vigilance states, the delta activity and EEG energy over the light- and dark-period.

Animals↗

Urinary levels of 3-methoxy-4-hydroxyphenylglycol predict symptom severity in selected patients with unipolar depression.

There are preliminary biological data that support the validity of subtyping depressed patients by family history into depressive spectrum disease (DSD) and non-DSD groups. We hypothesized that a relatively homogeneous group of depressed patients might show an association between symptom severity and the norepinephrine metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG). Twenty-four patients with non-DSD depression showed a relationship between urinary levels of MHPG and the severity of several depressive symptoms. There were no associations between MHPG and symptom severity for 38 DSD patients. This study provides additional support for the validity of family history approaches to subtyping depression. The data also suggest that norepinephrine may be involved in some way in the pathogenesis of symptoms in non-DSD depression.

Adult↗

DNA double-strand damage and repair following gamma-irradiation in isolated spermatogenic cells.

Various cell types in spermatogenesis exhibit differential sensitivity to radiation-induced DNA damage. The investigation of DNA radiosensitivity in vitro is complicated by the heterogeneous population of male germ cells (MGC) present in isolated single-cell suspensions. In the present investigation, the neutral elution technique was used to assess gamma-irradiation-induced DNA double-strand damage (DSD) in spermatogonia and preleptotene spermatocytes (SG/PL), pachytene spermatocytes and spermatid spermatocytes, as well as in MGC. In addition, the capability of these cell types to repair DNA double-strand damage was investigated. Based on the well established timing of the rat spermatogenic cycle, the DNA of specific cell populations was labeled using tritiated thymidine. DNA from labeled cells was determined isotopically, whereas total DNA was quantitated using a fluorometric method. DSD was induced in a dose-dependent manner in the heterogeneous population as well as in the labeled cell populations. SG/PL were more sensitive to gamma-irradiation-induced DSD than either the heterogeneous MGC population, pachytene or spermatid spermatocytes. Each cell type exhibited a similar capability to repair DSD following exposure to 3000 rad; repair was rapid (maximal within 45 min) and incomplete (less than 40%). Only pachytene spermatocytes exhibited significant repair following exposure to 6000 rad. Since a difference in sensitivity to radiation-induced DSD was demonstrated, the capability of each cell type to repair a similar initial frequency of strand damage was investigated. SG/PL, pachytene and spermatid spermatocytes differed in their capability to repair similar levels of strand damage. However, the difference in dose required to achieve equal damage may have contributed to other cellular effects, thus altering repair. In summary, a model is described that permits the evaluation of genotoxic responses in specific populations of spermatogenic cells within a heterogeneous cell suspension. The ability of specific cell types to repair gamma-irradiation-induced DNA double-strand damage is demonstrated.

Animals↗

Understanding detrusor sphincter dyssynergia--significance of chronology.

OBJECTIVES: To evaluate in patients with spinal cord injury (SCI) and detrusor sphincter dyssynergia (DSD) whether the onset of external urethral sphincter (EUS) contractions precedes or follows the onset of bladder contractions and to address the issue of potential therapeutic approaches based on the understanding of DSD chronology. METHODS: A retrospective review of video-urodynamic recordings of patients with SCI that demonstrated both untreated neurogenic overactive bladder and DSD, from January 2002 to December 2003, was performed. Delay A was defined as the period between the onset of an EUS pressure increase and the onset of a bladder pressure increase and delay B as the period between the onset of a urethral sphincter pressure increase and the moment at which the bladder pressure increase reached 10 cm H2O greater than the baseline value. RESULTS: Twenty patients with traumatic SCI matched all inclusion criteria. Delay A was positive (EUS contracted first) in 16 (80%) of 20 patients. The mean time for delay A was 2.2 seconds. A positive association was found among a positive delay A, the completeness of the spinal lesion, and continuous DSD type. Delay B was positive in all 20 patients (100%). The mean time for delay B was 7.6 seconds. CONCLUSIONS: In most patients with SCI and DSD, the EUS contraction started before the onset of the bladder contraction. Additionally, in all patients with SCI, the EUS contraction started before the critical part of the bladder contraction. A pathophysiologic hypothesis for such chronology is discussed. A potential therapeutic application would be to use urethral sphincter activity to trigger inhibition of bladder contractions (conditional neuromodulation) and treat the neurogenic overactive bladder.

Humans↗

Modelling the effects of (green) antifungals, droplet size distribution and temperature on mould outgrowth in water-in-oil emulsions.

Prevention of fungal spoilage is a key microbiological issue for the shelf life of fat spreads. Our aim was to assess and model the scope of (natural) antimicrobials for extending shelf life of spreads (water-in-oil emulsions). Production conditions were established to make 60% model fat spreads with reproducible droplet size distributions. The mould vulnerabilities ranged from 1 to 20 weeks. The system allowed feasibility testing of lytic enzymes (Novozym 234) and LMW compounds against Penicillium roqueforti, a key-spoilage mould. The action of Novozym 234, carvacrol, undecanol and dihydrocarveol was benchmarked against sorbate and preservative-free controls under ambient and chilled conditions. Novozym 234 was ineffective to prevent outgrowth of P. roqueforti. Carvacrol, undecanol and dihydrocarveol had limited effects on shelf-life extension compared to sorbate. Fungal growth boundaries of (un-)preserved spreads were modelled. The emulsion droplet size distribution (DSD) was first captured in a mechanistic parameter DSD-I (I = Influence). DSD-I was a move away from the mean droplet diameter D3,3 as sole quantitative droplet-size distribution parameter for mould susceptibility of emulsions. DSD-I is a combination of available water droplets and surface area to initiate and sustain fungal outgrowth. Followup experiments showed that modelling D3,3 and distribution width (e(sigma)) instead of DSD-I gave better results for emulsions with high e(sigma). Empirical predictive models were subsequently developed for the effects of D3,3, e(sigma) and undissociated sorbic acid (HSO) on the shelf life of emulsions.

Antifungal Agents↗

Botulinum a toxin and detrusor sphincter dyssynergia: a double-blind lidocaine-controlled study in 13 patients with spinal cord disease.

OBJECTIVE: To compare the efficacy and tolerance of botulinum A toxin (BTx) versus lidocaine (L), applied in the external urethral sphincter with a single transperineal injection in order to treat detrusor sphincter dyssynergia (DSD) in spinal cord injured patients. METHODS: Thirteen patients (1F, 12 M) suffering from chronic urinary retention due to DSD were randomised to receive one transperineal injection of 100 IU BTx Botox degrees in 4 ml of 9% saline (botulinum group, (BG)) or 4 ml of 0.5% L (lidocaine group, (LG)). The main criteria of efficacy was post-voiding residual urine volume (PRUV), assessed three times daily on day one (D1), D7 and D30 after each injection. Other criteria were micturition diary, satisfaction score (SS), maximal urethral pressure (MUP), maximum detrusor pressure (DP) and type of DSD, recorded on D0 and D30. RESULTS: In the BG, there was a significant decrease in PRUV (D7: -141.4 ml (p<0.03); D30: -159.4 ml (p<0.01)), in MUP (D30: -32 cm H(2)O, p<0.04) whereas no significant improvement was shown in the LG. SS was higher in BG than LG (p<0.02). DSD improved in BG whereas it remained unchanged in LG. All LG patients also received one injection of BTx on D30. They still presented improvement in PRUV and MUP 1 month later (D30'). Tolerance appeared satisfactory in both groups. CONCLUSIONS: The preliminary results of this initial randomised double-blind study clearly demonstrated the superiority of BTx compared to L in improving clinical symptoms and urethral hypertonia associated with DSD in spinal cord injured patients.

Adult↗

Comparative study of the action of bovine duodenal proteinases (duodenases) on polypeptide substrates.

A comparative study of substrate specificity of bovine duodenal proteinases--chymotrypsin-like duodenase (ChlD) and dual-specificity duodenase (dsD)--was carried out using oligopeptide substrates (human proinsulin, glucagon, melittin, angiotensinogen fragment 1-14). ChlD displayed mainly chymotrypsin-like properties towards these substrates, hydrolyzing peptide bonds carboxy-terminally to bulky aliphatic or aromatic residues. In melittin, ChlD additionally cleaved peptide bonds after Thr and Ser residues. Dual-specificity duodenase (dsD) significantly restricted its specificity to only trypsin-like or only chymotrypsin-like or displayed full activity, combining both specificities, depending on substrate. Both ChlD and dsD efficiently hydrolyzed a single peptide bond (Phe8--His9) in angiotensinogen fragment 1-14. The kinetic parameters of angiotensinogen fragment 1-14 cleavage by ChlD and dsD were determined (k(cat)/K(m) = 80,500 M(-1) x sec(-1) for ChlD and 103,000 M(-1) x sec(-1) for dsD).

Amino Acid Sequence↗

Characteristic hexasaccharide sequences in octasaccharides derived from shark cartilage chondroitin sulfate D with a neurite outgrowth promoting activity.

A mouse brain chondroitin sulfate (CS) proteoglycan, DSD-1-PG, bears the DSD-1 epitope and has neurite outgrowth promoting properties. Shark cartilage CS-C inhibits the interactions between the DSD-1-specific monoclonal antibody 473HD and the CS chains of the DSD-1-PG, which is expressed on the mouse glial cells (Faissner, A., Clement, A., Lochter, A., Streit, A., Mandl, C., and Schachner, M. (1994) J. Cell Biol. 126, 783-799). On the other hand, several hexasaccharides isolated from commercial shark cartilage CS-D, which contains a higher proportion of characteristic D units (GlcUA(2-sulfate)beta1-3GalNAc(6-sulfate)) as compared with CS-C, has the A-D tetrasaccharide sequence composed of an A disaccharide unit (GlcUAbeta1-3GalNAc(4-sulfate)) and a D disaccharide unit (Nadanaka, S. and Sugahara, K. (1997) Glycobiology 7, 253-263). In this study, the biological activities and the structure of shark cartilage CS-D were investigated. CS-D inhibited the interactions between monoclonal antibody 473HD and DSD-1-PG and also promoted neurite outgrowth of embryonic day 18 hippocampal neurons. Eight octasaccharide fractions were isolated from CS-D after partial digestion with bacterial chondroitinase ABC by means of gel filtration chromatography and anion-exchange high performance liquid chromotography to investigate the frequency and the arrangement of the A-D tetrasaccharide unit in the polymer sequence. Structural analysis performed by a combination of enzymatic digestions with 500-MHz 1H NMR spectroscopy demonstrated that the isolated octasaccharides shared the common core structure DeltaHexAalpha1-3GalNAcbeta1-4(GlcUAbeta1-3GalNAc)3 with four, five, and six sulfate esters at various hydroxyl groups in different combinations. In the structure, DeltaHexA and GlcUA represent 4-deoxy-alpha-L-threo-hex-4-enepyranosyluronic acid and glucuronic acid, respectively. No D-D tetrasaccharide sequence was found, and discrete D disaccharide units were demonstrated exclusively as A-D tetrasaccharide units in either an A-D-A or an A-D-C hexasaccharide sequence in the five octasaccharides that represented about 5.0% (w/w) of the starting polysaccharides (C denotes the disaccharide GlcUAbeta1-3GalNAc(6-sulfate)). It remains to be determined whether such characteristic hexasaccharide sequences present in shark cartilage CS-D serve as functional domain structures recognized by some protein ligands.

Animals↗