Biomedical subjects

Francisco Cruz

Publications and source records attributed to Francisco Cruz.

26 records · Page 2Linked to original sources

PubMed2004

Botulinum toxin in the management of lower urinary tract dysfunction: contemporary update.

PURPOSE OF REVIEW: To review the most recent experience concerning the application of botulinum toxin in the human lower urinary tract. RECENT FINDINGS: Botulinum toxin was initially applied in the bladder of patients with spinal neurogenic detrusor overactivity and urinary incontinence, or in the urethra in cases of detrusor external sphincter dyssynergia. A large multicentric European study fully confirmed the initial expectancy in the former condition. In addition, the application of botulinum toxin was extended to the treatment of other urological disorders including non-neurogenic detrusor overactivity, non-relaxing urethral sphincter and detrusor underactivity. Interesting reports on the injection of botulinum toxin into the prostate of patients with benign prostatic hyperplasia are also reviewed. SUMMARY: Bladder injection of botulinum toxin is not yet an approved treatment for lower urinary tract dysfunction. Nevertheless, available data suggest that in the near future the toxin will become a standard therapeutic option in incontinent patients with neurogenic and non-neurogenic forms of overactive bladder, who do not respond to or do not tolerate anticholinergic medication. In addition, it might be expected that urethral botulinum toxin injections improve bladder emptying in patients with dysfunctional voiding problems besides detrusor external sphincter dyssynergia.

Adult↗

PubMed2004

Intravesical resiniferatoxin decreases spinal c-fos expression and increases bladder volume to reflex micturition in rats with chronic inflamed urinary bladders.

OBJECTIVE: To evaluate the effect of intravesical resiniferatoxin on spinal c-fos expression and bladder volume at reflex micturition in rats with chronic urinary bladder inflammation. MATERIALS AND METHODS: Of three groups of female Wistar rats, group 1 received cyclophosphamide (75 mg/kg body weight) intraperitoneally every third day (cyclophosphamide is an antitumoral agent that induces bladder inflammation after urinary excretion of its metabolite, acrolein); group 2 comprised sham-inflamed rats that received saline instead of cyclophosphamide, and group 3 received cyclophosphamide, as group 1, every third day but plus 10 nmol/L resiniferatoxin intravesically, through a urethral catheter, at 7 days. At 8 days, under urethane anaesthesia, a needle was inserted in the bladder dome and saline infused at 6 mL/h for 2 h. Finally the animals were perfusion-fixed through the ascending aorta with 4% paraformaldehyde. Transverse sections cut from L6 spinal cord segments were immunoreacted for Fos protein and positive cells in the dorsal horn counted. In a further set of equal groups the bladders were prepared in the same way under urethane anaesthesia and after 30-min of stabilization, saline was infused at 6 mL/h and the volume evoking reflex micturition determined. RESULTS: The mean (SD) number of positive c-fos cells per spinal cord section was 85 (21), 42 (9) (P = 0.002) and 55 (10) in groups 1 to 3, respectively; the values for group 2 and 3 were similar (P = 0.22) and statistically less than that of group 1 (P = 0.02). Reflex micturition occurred at, respectively, 0.26 (0.09), 0.49 (0.18) and 0.52 (0.11) mL, being similar in group 2 and 3 (P = 0.74) but lower in group 1 (P = 0.003). CONCLUSION: Intravesical resiniferatoxin decreases c-fos expression and increases bladder capacity in chronically inflamed rat bladders. These findings suggest that desensitizing the vanilloid receptor type 1 by intravesical resiniferatoxin is relevant to the treatment of pain and voiding frequency in patients with chronic inflammatory bladder conditions.

Animals↗

PubMed2003

A role for iron in an ancient carbonic anhydrase.

Since 1933, carbonic anhydrase research has focused on enzymes from mammals (alpha class) and plants (beta class); however, two additional classes (gamma and delta) were discovered recently. Cam, from the procaryote Methanosarcina thermophila, is the prototype of the gamma class and the first carbonic anhydrase to be characterized from either an anaerobic organism or the Archaea domain. All of the enzymes characterized from the four classes have been purified aerobically and are reported to contain a catalytic zinc. Herein, we report the anaerobic reconstitution of apo-Cam with Fe2+, which yielded Cam with an effective kcat that exceeded that for the Zn2+-reconstituted enzyme. Mössbauer spectroscopy showed that the Fe2+-reconstituted enzyme contained high spin Fe2+ that, when oxidized to Fe3+, inactivated the enzyme. Reconstitution with Fe3+ was unsuccessful. Reconstitution with Cu2+, Mn2+, Ni2+, or Cd2+ yielded enzymes with effective kcat values that were 10% or less than the value for the Zn2+-reconstituted Cam. Cam produced in Escherichia coli and purified anaerobically contained iron with effective kcat and kcat/Km values exceeding the values for Zn2+-reconstituted Cam. The results identify a previously unrecognized biological function for iron.

Archaea↗

PubMed2003

Insulin induces cobalt uptake in a subpopulation of rat cultured primary sensory neurons.

Previous findings show that both the vanilloid receptor 1 and the insulin receptor are expressed on small primary sensory neurons. As insulin evokes activity in second messengers which could induce opening of the vanilloid receptor 1, we examined, by using the cobalt-uptake technique, whether or not insulin can activate cultured rat primary sensory neurons through activating the vanilloid receptor 1. Capsaicin (50, 100 and 500 nm) induced concentration-dependent labelling in primary sensory neurons. Preincubation of cells in insulin (10 micromoles) for 10 min followed by a 2-min wash did not produce significant change in the capsaicin-induced labelling. Coapplication of insulin (10 micromoles) with capsaicin, however, potentiated the 50 and 100 nm capsaicin-evoked staining. Insulin itself also produced cobalt labelling in a concentration-dependent manner. The size-frequency distributions of neurons showing capsaicin- or insulin-induced cobalt accumulation were similar. The insulin-induced cobalt labelling was significantly reduced by the tyrosine kinase inhibitor, tyrphostin AG1024, the vanilloid receptor 1 antagonists, ruthenium red and capsazepine, the protein kinase inhibitor, staurosporine and the phospholipase C inhibitor neomycin. Double immunostaining of cultured primary sensory neurons and sections from dorsal root ganglia revealed that about one-third of the cells coexpress the insulin receptor and vanilloid receptor 1. These findings suggest that insulin activates a subpopulation of primary sensory neurons, probably through phosphorylation- and/or phosphatidylinositol(4,5)biphosphate hydrolysis-evoked activation of the vanilloid receptor 1. Although the insulin-induced activation of vanilloid receptor 1 seems to be a short-lived effect in vitro, in vivo it might play a role in the development of burning pain sensation in hyperinsulinism.

Animals↗

PubMed2002

Nerve growth factor regulates galanin and c-jun overexpression occurring in dorsal root ganglion cells after intravesical resiniferatoxin application.

Galanin and c-jun expression after a single bladder instillation of resiniferatoxin was studied by immunocytochemistry in L6 dorsal root ganglia (DRG) neurons of the rat. The role of nerve growth factor depletion in causing that effect was also investigated. Three days after instillation of a 100 nM resiniferatoxin solution a marked increase in the number of galanin and c-Jun immunoreactive DRG cells was evident bilaterally. The increments were still present at 8 days and disappeared 1 month after treatment. Systemic administration of nerve growth factor, 100 microg/kg, prevented both overexpressions. Results suggest that the changes induced in bladder sensory neurons by intravesical resiniferatoxin are due, at least in part, to the temporary deprivation of bladder-derived neurotrophic factors, namely nerve growth factor, in those neurons.

Animals↗

PubMed2002

Vanilloid receptor and detrusor instability.

Very recently, a membrane receptor (vanilloid receptor type 1 [VR-1]) sensitive to capsaicin or resiniferatoxin (RTX) was identified in small- and medium-sized dorsal root ganglion neurons that give rise to most unmyelinated sensory fibers. After vanilloid binding to VR-1, these neurons remain transiently desensitized; that is, less reactive to natural stimuli. It is this effect of vanilloid substances that is being investigated for its potential therapeutic utility. In the urinary bladder, VR-1-expressing fibers are extremely abundant in the mucosa and in the muscular layer. In the latter, VR-1 fibers are intimately apposed to smooth muscle cells. The demonstration, several years ago, that these fibers were involved in detrusor hyperreflexia of spinal origin and in bladder pain processing, justified the clinical application of intravesical capsaicin or RTX in humans with these bladder diseases. More recently, the experimental and clinical evidence that the same type of bladder sensory fibers were also involved in detrusor instability made a strong case for intravesical RTX assay in patients with idiopathic detrusor instability.

Animals↗

PubMed2002

The effect of intravesical resiniferatoxin in patients with idiopathic detrusor instability suggests that involuntary detrusor contractions are triggered by C-fiber input.

PURPOSE: We evaluated the role of bladder C-fiber input in involuntary detrusor activity in patients with idiopathic detrusor instability. MATERIALS AND METHODS: Filling cystometry and a voiding chart were done in 13 patients with idiopathic detrusor instability. The first detrusor contraction, maximal cystometric capacity, daily frequency and the number of episodes of urinary incontinence were determined. A 50 nM. solution of resiniferatoxin, a specific C-fiber neurotoxin, was then instilled in the bladder for 30 minutes. Patients were reevaluated 30 and 90 days later. RESULTS: Resiniferatoxin instillation delayed or suppressed involuntary detrusor contractions during filling cystometry. The mean first detrusor contraction plus or minus standard deviation increased from 170 +/- 109 ml. at baseline to 440 +/- 130 ml. (p = 0.0001) at 30 days and to 391 +/- 165 ml. (p = 0.008) at 90 days. Mean maximal cystometric capacity increased from 291 +/- 160 to 472 +/- 139 ml. (p = 0.01) at 30 days and to 413 +/- 153 ml. (p = 0.1) at 90 days. The mean number of episodes of urinary incontinence daily decreased from 4.3 +/- 2.7 to 0.9 +/- 2.7 (p = 0.001) at 30 days and to 0.7 +/- 0.9 (p = 0.009) at 90 days. Mean frequency daily also decreased from 12 +/- 3.2 to 9.7 +/- 3.2 (p = 0.003) and to 9.9 +/- 3.5 (p = 0.001) times at the same time points, respectively. CONCLUSIONS: C-fiber input seems to have an important role in the generation of involuntary detrusor contractions and lower urinary tract symptoms in patients with idiopathic detrusor instability. Substances that block C-fiber input may represent a new strategy for treating this bladder dysfunction.

Administration, Intravesical↗

PubMed1996

Desensitization follows excitation of bladder primary afferents by intravesical capsaicin, as shown by c-fos activation in the rat spinal cord.

Activation of the protooncogene c-fos at spinal cord segments T12-L2 and L5-S1 was used to study the effects of topical administration of capsaicin on bladder primary afferents coursing in the hypogastric (HGN) or pelvic (PN) nerves of adult rats. Two hours after capsaicin instillation in the bladder numerous Fos cells occurred in lamina I at T12-L2 and in lamina I, intermediolateral gray matter (ILG) and dorsal commissure (DCM) at L5-S1. Twenty-four hours later, the Fos immunoreaction had disappeared from the spinal cord. At this time, instillation of 1% acetic acid into the bladder of capsaicin-treated rats induced considerably fewer Fos cells than in animals that had been instilled only with the vehicle solution for capsaicin. The difference in the average number of Fos cells was statistically significant in lamina I, ILG and DCM at L5-S1 but not in lamina I at T12-L2. Thus, intravesical capsaicin at the doses used excites bladder primary afferents coursing in the HGN and PN, but only desensitizes those coursing in the PN. It is suggested that this may depend on the differential occurrence of capsaicin receptors in the two nerves.

Acetic Acid↗