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Biomedical subjects

C Silva

Publications and source records attributed to C Silva.

At least 37 records · Page 2Linked to original sources
PubMed2002

[Pharmacological treatment of obesity].

The foundation on which the treatment of obesity rests is made up of the procedures aimed at unbalancing the equation of energy balance in favour of calorie consumption. Pharmacological treatment is aimed at favouring a reduction of calorie intake or stimulating calorie production. Depending on their mechanism of action, the drugs that are used in the treatment of obesity can be divided into appetite inhibitors, inhibitors of food intake or blockers of fat digestion and stimulators of thermogenesis. Amongst the appetite inhibitors, besides the adrenergic agents such as those of the amphetamine type, which are forbidden because of their addictive effect, are the serotonin uptake inhibitors such as dexfenfluramine (withdrawn in 1997) and fluoxetine. The recent commercialisation of sibutramine, a serotonin and norepinephrine reuptake inhibitor with an appetite inhibiting and thermogenesis stimulating effect, offer new perspectives in this field. Amongst inhibitors, mention is deserved by orlistat that inhibits the absorption of upto 30% of ingested fat without causing secondary effects of significance. In the area of thermogenic drugs there are the ephedrine-caffeine association, and the adrenergic beta antagonists, which are still being researched. There are numerous future perspectives amongst which are leptin, analogs of GLP-1 and cholecystokinin and neuropeptide Y antagonists. It is necessary to have reliable predictive elements that make it possible to know the most useful drugs, as well as the sort of patients who will benefit most from the different pharmacological treatments.

English Abstract↗
PubMed2001

HIV-1 Tat neurotoxicity is prevented by matrix metalloproteinase inhibitors.

The release of potentially neurotoxic molecules by HIV-infected brain macrophages is accompanied by neuronal injury and death that results in the development of HIV-associated dementia (HAD). Among the potential neurotoxins implicated in the development of HAD is the HIV-1 transactivating protein, Tat. To investigate the mechanism by which Tat causes neurotoxicity, brain-derived Tat sequences from nondemented (Tat-ND) and demented (Tat-HAD) AIDS patients, which differed primarily in the augmenting region of Tat, were expressed in U937 monoblastoid cells and primary human macrophages. Cells expressing Tat-HAD protein exhibited elevated matrix metalloproteinase (MMP)-2 and -7 release and activation, but cells expressing Tat-ND did not exhibit enhanced MMP expression. Conditioned media from Tat-HAD-transfected cells caused significantly greater neuronal death (15.4 +/- 4.3%) than did Tat-ND (4.4 +/- 2.1%) or nontransfected (2.1 +/- 0.8%) cell-derived conditioned media. The neurotoxicity induced by Tat-HAD was inhibited by anti-MMP-2 or -7 antibodies (p < 0.005) but not by antibodies against MMP-9 or Tat. Similarly, scid/nod mice receiving striatal implants of Tat-HAD-transfected cells exhibited greater neurobehavioral abnormalities and neuronal loss (p < 0.005) than did animals receiving Tat-ND or nontransfected cells, which were reduced by treatment with the MMP inhibitor prinomastat (p < 0.005). These findings indicate that Tat causes neuronal death through an indirect mechanism that is Tat sequence dependent and involves the induction of MMPs.

AIDS Dementia Complex↗
PubMed2001

Monocyte activation and differentiation augment human endogenous retrovirus expression: implications for inflammatory brain diseases.

Human endogenous retroviruses (HERVs) have been implicated as causative agents in diseases characterized by inflammation and macrophage activation, such as multiple sclerosis. Because monocyte activation and differentiation influence retroviral transcription and replication, we investigated the contribution of these processes to the expression of four HERV families (HERV-W, HERV-K, HERV-E, and HERV-H) in human monocytes, and autopsied brain tissue from patients with brain diseases associated with increased macrophage activity. Reverse transcriptase-polymerase chain reaction analysis of primary macrophages and U937 monocytoid cells stimulated with phorbol-12-myristate-13-acetate or lipopolysaccharide revealed three- to ninefold increases in HERV-W, HERV-K, and HERV-H RNA levels. In addition, elevated reverse transcriptase activity and HERV RNA were detectable in supernatants from PMA-stimulated U937 cultures, properties that could be attenuated with the inhibitor of monocyte differentiation threonine-lysine-proline. In contrast, stimulation of monocytes decreased or had no effect on HERV-E expression. Compared with controls, HERV-W and HERV-K expression was increased in brain tissue from patients with multiple sclerosis or human immunodeficiency virus infection or AIDS, with concomitant elevated tumor necrosis factor-alpha levels. Similarly, elevated HERV-W levels were detected in patients with Alzheimer's dementia only when tumor necrosis factor-alpha expression was also evident (2 of 6 cases). The detection of several HERVs in inflammatory brain diseases and the capacity to augment HERV expression in monocytes with compounds that influence cellular activity suggest that increased expression of these viruses is a consequence of increased immune activity rather than causative of distinct diseases.

Adult↗
PubMed2001

Natural selection at the MJD locus: phenotypic diversity, survival and fertility among Machado-Joseph Disease patients from the Azores.

Machado-Joseph Disease (MJD) is an autosomal dominant neurodegenerative disorder of adult onset, associated with the expansion of a (CAG)n tract in the coding region of the causative gene, localized on 14q32.1. Machado-Joseph Disease shows non-Mendelian features typical of other triplet repeat disorders, including clinical heterogeneity, variable age at onset and anticipation. Three phenotypes have been proposed (clinical types 1, 2 and 3). Type 1 is associated with early age at onset and a high repeat number of the CAG sequence, and Types 2 and 3 have later onset and lower numbers of CAG repeats. This paper investigates whether there is selection against the MJD gene, acting through differential survival. nuptiality and fertility associated with clinical type and age at onset. The study sample comprised 40 MJD patients from the Azores (Portugal) having fully documented reproductive histories and known dates of death. The proportion of married patients of each clinical type increased from 0.22 among Type 1 patients, to 0.40 in Type 2 and 0.95 in Type 3. Age at onset and length of survival were also associated with marital status, with the married cases having later mean age at onset and longer mean survival time. In the whole sample, clinical type was associated with fertility, with significantly fewer children born to Type 1 patients. Among married patients clinical type was not associated with age at marriage, reproductive span or number of children. No reduction of fertility was detected among married patients in whom the onset of MJD was below the age of 50. The authors' interpretation of these results is that the high-repeat CAG haplotypes associated with early age at onset and clinical Type 1 are selected against through reduced survival and fertility. The fertility component of selection is mediated by nuptiality rather than marital fertility.

Adolescent↗
PubMed2001

Encephalopathy with staphylococcal endocarditis: multiple neuropathological findings.

BACKGROUND: Infective endocarditis is associated with serious neurological sequelae. OBJECTIVE: Here, we report a patient with Staphylococcus aureus endocarditis, secondary to congenital heart disease, with subacute onset of multiple neurological complications. RESULTS: Despite prompt antibiotic treatment with rapid sterilization of blood cultures, the patient died with brain herniation within 96 hours of admission. Neuropathological examination showed intraparenchymal hemorrhages, mycotic aneurysms, micro-abscesses and septic arteritis with accompanying infarction. Immunocytochemical studies revealed enhanced CD45 and GFAP immunoreactivity, together with adenosine A1 receptor detection on macrophages and microglia. CONCLUSIONS: Infective endocarditis is associated with multiple neuropathological lesions, which may contribute to its poor clinical outcome and activation of cells of monocyte-microglial lineage throughout the brain.

Adult↗
PubMed2001

Clinical and genetic heterogeneity in hereditary haemochromatosis: association between lymphocyte counts and expression of iron overload.

To identify a new marker of expression of disease, independent of HFE genotype in patients with hereditary haemochromatosis (HHC), the total peripheral blood lymphocyte counts were analysed according to iron status in two groups of subjects with HFE mutations. The groups consisted of 38 homozygotes for C282Y, and 107 heterozygotes for the C282Y or compound heterozygotes for C282Y and H63D. For control purposes, total lymphocyte counts and iron status were also examined in 20 index patients with African dietary iron overload, a condition not associated with HFE mutations, and in 144 members of their families and communities. Mean lymphocyte numbers were lower in C282Y homozygous HHC index subjects with cirrhosis and higher iron stores than in those without cirrhosis and with lower iron burdens [(1.65 +/- 0.43) x 10(6)/mL vs. (2.27 +/- 0.49) x 10(6)/mL; p = 0.008]. Similarly, mean lymphocyte counts were significantly lower in C282Y heterozygotes and C282Y/H63D compound heterozygotes with iron overload and increased serum ferritin concentrations compared to those with normal serum ferritin concentrations (p < 0.05). Statistically significant negative correlations were found, in males, between lymphocyte counts and the total body iron stores, either in C282Y homozygous HHC patients (p = 0.031 in a multiple regression model dependent on age) and in C282Y heterozygotes or C282Y/H63D compound heterozygotes with iron overload (p = 0.029 in a simple linear model). In contrast, lymphocyte counts increased with increasing serum ferritin concentrations among the index subjects with African iron overload (r = 0.324, not statistically significant) and among the members of their families and communities (r = 0.170, p = 0.042). These results suggest that a lower peripheral blood lymphocyte count is associated with a greater degree of iron loading in HFE haemochromatosis but not in African iron overload, and they support the notion that the lymphocyte count may serve as a marker of a non-HFE gene that influences the clinical expression of HFE haemochromatosis.

Adult↗
PubMed2001

A light- and electron-microscopic histopathological study of human bladder mucosa after intravesical resiniferatoxin application.

OBJECTIVE: To determine the morphology of bladder mucosa and the integrity of its mucin coat in patients with detrusor hyper-reflexia treated with intravesical resiniferatoxin. PATIENTS AND METHODS: Seven patients with detrusor hyper-reflexia were treated intravesically with resiniferatoxin dissolved in 10% ethanol in saline (50 nmol/L solution in two and 100 nmol/L in five). Patients were clinically evaluated by a voiding chart and filling cystometry before and 3 months after each resiniferatoxin application. In addition, they underwent cystoscopy and bladder biopsies at 22-33 months after the first instillation and at 7-23 months after the last one. Tissue samples for light microscopy were fixed in 4% paraformaldehyde, embedded in paraffin and stained with haematoxylin-eosin or periodic acid-Schiff reagent (PAS). Those for electron microscopy were fixed in 5% glutaraldehyde and embedded in resin. RESULTS: The resiniferatoxin instillation was not painful. Three months after treatment the mean voiding frequency decreased and five incontinent patients became continent. The maximum cystometric capacity increased in all patients; at cystoscopy the bladders appeared normal. On light microscopy the urothelium was of normal morphology and stained with PAS in the luminal cells and in the basement membrane. Mononuclear inflammatory cells were occasionally apparent in the lamina propria. On electron microscopy epithelial cells were visible in a thick basal lamina. Superficial cells had the usual irregular contour and contained numerous membrane-coated vesicles. In the lamina propria, unmyelinated axonal profiles with occasional varicosities could be identified. CONCLUSIONS: Intravesical resiniferatoxin improved urinary frequency, incontinence and bladder capacity in patients with detrusor hyper-reflexia, causing no morphological change in the bladder mucosa. The PAS reactivity of the carbohydrate moieties present in the mucin coat and the basement membrane was unchanged by resiniferatoxin.

Administration, Intravesical↗
PubMed2001

T-cell reactivity against streptococcal antigens in the periphery mirrors reactivity of heart-infiltrating T lymphocytes in rheumatic heart disease patients.

T-cell molecular mimicry between streptococcal and heart proteins has been proposed as the triggering factor leading to autoimmunity in rheumatic heart disease (RHD). We searched for immunodominant T-cell M5 epitopes among RHD patients with defined clinical outcomes and compared the T-cell reactivities of peripheral blood and intralesional T cells from patients with severe RHD. The role of HLA class II molecules in the presentation of M5 peptides was also evaluated. We studied the T-cell reactivity against M5 peptides and heart proteins on peripheral blood mononuclear cells (PBMC) from 74 RHD patients grouped according to the severity of disease, along with intralesional and peripheral T-cell clones from RHD patients. Peptides encompassing residues 1 to 25, 81 to 103, 125 to 139, and 163 to 177 were more frequently recognized by PBMC from RHD patients than by those from controls. The M5 peptide encompassing residues 81 to 96 [M5(81-96) peptide] was most frequently recognized by PBMC from HLA-DR7+ DR53+ patients with severe RHD, and 46.9% (15 of 32) and 43% (3 of 7) of heart-infiltrating and PBMC-derived peptide-reactive T-cell clones, respectively, recognized the M5(81-103) region. Heart proteins were recognized more frequently by PBMC from patients with severe RHD than by those from patients with mild RHD. The similar pattern of T-cell reactivity found with both peripheral blood and heart-infiltrating T cells is consistent with the migration of M-protein-sensitized T cells to the heart tissue. Conversely, the presence of heart-reactive T cells in the PBMC of patients with severe RHD also suggests a spillover of sensitized T cells from the heart lesion.

Antigen Presentation↗
PubMed2001

Progesterone does not alter osmotic regulation of AVP.

To test the hypothesis that progesterone, independent of estrogen, decreases the plasma osmotic threshold for arginine vasopressin (AVP) release and thirst onset, we compared AVP and thirst responses to hypertonic saline infusion (HSI) during administration of oral contraceptives (OCs) containing progesterone (OCP) with responses to infusion of OCs containing progesterone and estrogen (OCEP). Eight women (29 +/- 2 yr) were infused with 3% NaCl (120 min, 0.1 ml. kg body wt(-1). min(-1)) and consumed fluid (90 min, 15 ml/kg body wt) in the early follicular and midluteal phases of a 28-day menstrual cycle and also after 4 wk of OCP and after 4 wk of OCEP in a randomized crossover design. Baseline plasma osmolality (P(osm)) was lower in the luteal phase (280 +/- 1 mosmol/kgH(2)O) and during OCEP (283 +/- 1 mosmol/kgH(2)O) than in the follicular phase (286 +/- 1 mosmol/kgH(2)O, P < 0.05) but was unaffected by OCP (284 +/- 1 mosmol/kgH(2)O). P(osm) remained lower in the follicular phase than in the luteal phase and with OCEP throughout the first 50 min of HSI. The mean abscissal plasma AVP concentration-P(osm) intercept was unaffected by OCP (267 +/- 1 mosmol/kgH(2)O) but was greater in the follicular phase (273 +/- 2 mosmol/kgH(2)O) than in the luteal phase (266 +/- 4 mosmol/kgH(2)O) and with OCEP (268 +/- 2 mosmol/kgH(2)O, P < 0.05). There were no differences in osmotic thresholds for thirst onset across experimental days. Despite the lower osmotic threshold for AVP release during the luteal phase and with OCEP, fluid balance, renal free water clearance, and Na(+) regulation during HSI were unaffected by menstrual phase or OC treatment, indicating a lower osmotic operating point for body water balance. OCP did not affect osmotic AVP regulation, suggesting that progesterone does not affect osmotic fluid regulation through a mechanism independent of estrogen.

Adult↗
PubMed2001

Diminished adenosine A1 receptor expression on macrophages in brain and blood of patients with multiple sclerosis.

The nucleoside adenosine has been shown to control the production of proinflammatory molecules through its actions on cell surface purine receptors. Previously, we have reported that the adenosine A1 receptor (A1AR) regulates tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) expression and exhibits diminished function in patients with multiple sclerosis (MS; Mayne et al., Ann Neurol 1999;45:633-639). In the present study, A1AR expression in both brain and peripheral blood mononuclear cells (PBMC) from MS and control groups was characterized by fluorescence-activated cell sorting (FACS), reverse transcriptase-polymerase chain reaction (RT-PCR), and immunohistochemical analyses. FACS analyses of PBMC revealed that A1AR expression was chiefly detectable on CD14-positive cells and was reduced by 53.1% (p < 0.01) in MS patients compared to controls. A1AR mRNA levels were reduced by 43.1% (p < 0.001) in the brains of MS patients compared to patients with other neurological diseases and controls. A1AR protein expression in brain was detected primarily in CD45-positive glial cells and was markedly diminished in MS patients. The analysis of A1AR transcripts in the brain revealed that the A1AR-beta transcript was diminished (49.2%) in MS patients compared to controls (p < 0.002). These results indicate that the A1AR, expressed principally on cells of monocyte/macrophage lineage in both brain and blood, is selectively diminished in MS patients. Reduction of the A1AR-beta transcript in MS patients suggests that dysregulated splicing may influence A1AR protein levels, potentially leading to increased macrophage activation and central nervous system inflammation.

Brain↗
PubMed2001

Conventional and conventional plus modified ultrafiltration during cardiac surgery in high-risk congenital heart disease.

BACKGROUND: This prospective nonrandomized study is the critical assessment of conventional ultrafiltration (CUF) and modified ultrafiltration (MUF) techniques and their efficiency in congenital heart disease surgeries. Use of cardiopulmonary bypass (CPB) in children is associated with body water retention as a consequence of prime volume and systemic inflammatory reaction. The CUF during CPB has reduced body water excess and the MUF after CPB, removes inflammatory mediators, improves hemodynamic performance, and decreases transfusion requirements. METHODS: Forty-one patients, aged 9 to 36 months, submitted to surgical correction for cardiac defects, using CPB, were divided into 2 similar groups: CUF (21 patients) operated between 1996-1997 were ultrafiltered during CPB, and CUF+MUF, (20 patients) operated between 1997-1998 and ultrafiltered during and after CPB. Postoperative duration of ventilator support, pediatric intensive care unit stay (PICU), hospital stay of the groups with and without preoperative pulmonary hypertension (PH), as well as transfusion requirement, hematocrit and platelet counts were compared. RESULTS: There were no technical complications and a significant ultrafiltrate in the CUF+MUF group was observed as compared to the CUF group. No significant differences were observed between the CUF and CUF+MUF groups regarding ventilatory support, PICU stay and hospital stay. Requirements for red cell transfusion, Ht and platelet counts were not statistically different. CONCLUSIONS: CUF and CUF+MUF were safe and efficient methods for patient stabilization independent of diagnosis and complexity of surgery. Future clinical evaluation should address a larger population of patients to research the different variables.

Algorithms↗
PubMed2000

Reconstruction of the pulmonary valve and outflow tract with bicuspid prosthesis in tetralogy of Fallot.

BACKGROUND: Right ventricular outflow tract and pulmonary valve implant in patients with tetralogy of Fallot may be required to avoid late postoperative right ventricular impairment. The use of porcine bicuspid prosthesis might be a technical alternative, although comprehensive studies on the long-term use of these prostheses are not available. METHODS: Sixty-three patients (aged 5 months to 34 years; mean, 6 years) with tetralogy of Fallot and pulmonary hypoplasia underwent surgical repair and enlargement of the right ventricular outflow using preserved porcine pulmonary bicuspid prostheses. Fifty-two patients (82.5%) were followed and underwent clinical evaluation and serial Doppler echocardiography. The first 15 patients (29.4%), with ages ranging from 5 to 16 years (mean, 8.2 years) and postoperative follow-up of 48 to 87 months (mean, 65.1 months) underwent hemodynamic and cineangiographic evaluations. RESULTS: There were 11 deaths (17.4%) in the early postoperative period. Of the 52 surviving patients (82.5%), 51 (80.9%) were followed for 1 to 87 months (mean, 42.0 months). Four patients (7.6%) had additional treatment. Of the 15 patients (29.1%) undergoing hemodynamic evaluation, 9 (60%), had mild valvular pulmonary insufficiency and 6 (40%) had moderate insufficiency. Only the right ventricle-to-pulmonary artery pressure gradients and the right ventricular ejection fraction showed statistically significant differences between groups. Right ventricular dimension, although increased in all patients, did not show statistically significant differences. CONCLUSIONS: Right ventricular outflow tract and pulmonary valve repair in patients with tetralogy of Fallot using a bicuspid porcine pulmonary prosthesis is a simple, reliable procedure with good results in postoperative medium term follow-up.

Adolescent↗
PubMed2000

Structure-property relationships on histamine H3-antagonists: binding of phenyl-substituted alkylthioimidazole derivatives to rat plasma proteins.

The binding of a series of H3-antagonists to rat plasma proteins was investigated by dialysis experiments, with RP-HPLC measurement of the free ligand. The series was composed of 4(5)-phenyl-2-[[2-[4(5)-imidazolyl]ethyl]thio]imidazoles having, on the phenyl ring, meta- and para-substituents, with different physico-chemical characteristics. As high protein binding had been proposed as being one of the features limiting brain access for the reference H3-antagonist thioperamide, the title series was employed to test the possibility of achieving lower protein binding by modulation of lipophilicity, while maintaining good receptor affinity. The compounds tested showed quotas of bound drug ranging from 60 to 97.5%, while for thioperamide a 78% bound drug quota was observed at high total concentrations, with a steep increase in bound percentage at lower concentrations. Two of the tested compounds, having a carboxamide substituent, showed lower protein binding compared to thioperamide over a wide range of total concentration, without a significant loss in affinity with respect to the parent compound. A strict dependence of protein binding on lipophilicity was observed, and a QSPR model was derived which could also account for the protein binding observed for thioperamide, while receptor affinity had been reported to be quite insensitive to phenyl ring substitution. It is therefore possible to modulate protein binding of these H3-antagonists, through lipophilicity adjustment, without losing receptor affinity; this finding could help in the design of new compounds with improved brain access.

Animals↗
PubMed2000

Synthesis and biological assays of new H3-antagonists with imidazole and imidazoline polar groups.

New histamine H3-receptor antagonists were synthesised and tested on rat brain membranes and on electrically stimulated guinea-pig ileum. The new compounds have a central polar group represented by a 2-alkylimidazole or a 2-thioimidazoline nucleus. The effect of the polar group basicity on the optimal length of the alkyl chain, connecting this group to a 4(5)-imidazolyl ring, was investigated. The best affinity values, obtained by displacement of [3H]-RAMHA from rat brain, were obtained for the 2-alkylimidazole derivatives (2a-f) with tetramethylene chain (pKi 8.03-8.97), having an intermediate basicity between that of the previously reported 2-thioimidazoles (1a-i) and that of 2-alkylthioimidazolines (3a-h). In contrast, a general lowering of affinity (pKi 5.90-7.63) was observed for compounds of the last series (3a-h), with a complex dependence on the terminal lipophilic group and chain length.

Animals↗
PubMed2000

Prognostic value of Ki-67 expression in localized cutaneous malignant melanoma.

BACKGROUND: The proliferative activity of some tumors is related to the development of metastatic disease and survival. Thus it could be used as a potential prognostic variable. OBJECTIVE: The purpose of this study was to determine the prognostic value of the Ki-67 index and of a "proliferation-based prognostic index" (PBPI, derived as tumor thickness x Ki-67 index/100) in localized cutaneous malignant melanoma (CMM). METHODS: The Ki-67 index (percent of total tumor nuclei) was determined in a series of 84 localized CMMs, with the use of the alkaline phosphatase-antialkaline phosphatase labeling method in formalin-fixed, paraffin-embedded material, and was correlated with other prognostic variables. Survival analysis was performed to determine whether the Ki-67 index and the PBPI could be predictive of metastatic spread or recurrent disease. A stratified analysis of these two parameters according to the tumor thickness was done. RESULTS: An association among the Ki-67 index and location, Clark level, tumor thickness and stage, and prognostic index was detected. Increased Ki-67 index and PBPI were associated with poorer overall survival (P =.03 and P <.0001, respectively) and disease-free survival (P =.01 and P <.0001, respectively). However, after stratification for thickness, only the PBPI showed independent prognostic significance, restricted to tumors thicker than 4 mm (P =. 03). CONCLUSION: The determination of the PBPI in CMM conveys prognostic information for localized thick (>4 mm) CMM, identifying two groups of patients with distinct outcome.

Biomarkers↗
PubMed2000

Estrogen modifies the temperature effects of progesterone.

To test the hypothesis that progestin-mediated increases in resting core temperature and the core temperature threshold for sweating onset are counteracted by estrogen, we studied eight women (24 +/- 2 yr) at 27 degrees C rest, during 20 min of passive heating (35 degrees C), and during 40 min of exercise at 35 degrees C. Subjects were tested four times, during the early follicular and midluteal menstrual phases, after 4 wk of combined estradiol-norethindrone (progestin) oral contraceptive administration (OC E+P), and after 4 wk of progestin-only oral contraceptive administration (OC P). The order of the OC P and OC E+P were randomized. Baseline esophageal temperature (T(es)) at 27 degrees C was higher (P < 0.05) in the luteal phase (37.08 +/- 0.21 degrees C) and in OC P (37.60 +/- 0.31 degrees C) but not during OC E+P (37.04 +/- 0.23 degrees C) compared with the follicular phase (36.66 +/- 0.21 degrees C). T(es) remained above follicular phase levels throughout passive heating and exercise during OC P, whereas T(es) in the luteal phase was greater than in the follicular phase throughout exercise (P < 0.05). The T(es) threshold for sweating was also greater in the luteal phase (38.02 +/- 0.28 degrees C) and OC P (38.07 +/- 0.17 degrees C) compared with the follicular phase (37.32 +/- 0.11 degrees C) and OC E+P (37.46 +/- 0.18 degrees C). Progestin administration raised the T(es) threshold for sweating during OC P, but this effect was not present when estrogen was administered with progestin, suggesting that estrogen modifies progestin-related changes in temperature regulation. These data are also consistent with previous findings that estrogen lowers the thermoregulatory operating point.

Adult↗
PubMed2000

Desensitization of bladder sensory fibers by intravesical resiniferatoxin, a capsaicin analog: long-term results for the treatment of detrusor hyperreflexia.

OBJECTIVES: To assess the pungency and the desensitizing effects of intravesical resiniferatoxin, an ultrapotent capsaicin analog, in patients with detrusor hyperreflexia. METHODS: Fourteen patients with detrusor hyperreflexia were instilled during 30 min, without any form of local anesthesia, with 100 ml (or the bladder capacity if lower than that volume) of 50 or 100 nM resiniferatoxin solutions in 10% alcohol in saline. Patients were evaluated by voiding chart and urodynamic tests (volume to first contraction, maximal cystometric capacity, maximal detrusor pressure, icewater test) at 14, 30, 60, and 90 days and every 3 months thereafter RESULTS: Resiniferatoxin instillation did not evoke pain or temporary worsening of urinary symptoms. Treatment improved or abolished incontinence in 9 out of 12 incontinent patients. Mean urinary frequency decreased from 14.2+/-6.4 to 10.3+/-3.2 at 3 months (p = 0.01). At this time point, mean maximal cystometric capacity increased from 182.3+/-119.8 to 330.0+/-201.6 ml (p = 0.01) and the ice water test, positive in 13 cases, became negative in 8 of them. Maximal detrusor pressure was not modified by the treatment. The effect was long-lasting, reaching 12 months in 7 cases. CONCLUSIONS: The absence of irritative symptoms during bladder instillation of resiniferatoxin and the rapid onset of desensitization make this vanilloid superior to capsaicin for the treatment of detrusor hyperreflexia.

Administration, Intravesical↗