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1.
J Am Chem Soc ; 144(40): 18532-18544, 2022 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-36178375

RESUMEN

The majority of bioactive molecules act on membrane proteins or intracellular targets and therefore needs to partition into or cross biological membranes. Natural products often exhibit lipid modifications to facilitate critical molecule-membrane interactions, and in many cases their bioactivity is markedly reduced upon removal of a lipid group. However, despite its importance in nature, lipid-conjugation of small molecules is not commonly used in chemical biology and medicinal chemistry, and the effect of such conjugation has not been systematically studied. To understand the composition of lipids found in natural products, we carried out a chemoinformatic characterization of the "natural product lipidome". According to this analysis, lipidated natural products predominantly contain saturated medium-chain lipids (MCLs), which are significantly shorter than the long-chain lipids (LCLs) found in membranes and lipidated proteins. To study the usefulness of such modifications in probe design, we systematically explored the effect of lipid conjugation on five different small molecule chemotypes and find that permeability, cellular retention, subcellular localization, and bioactivity can be significantly modulated depending on the type of lipid tail used. We demonstrate that MCL conjugation can render molecules cell-permeable and modulate their bioactivity. With all explored chemotypes, MCL-conjugates consistently exhibited superior uptake or bioactivity compared to LCL-conjugates and either comparable or superior uptake or bioactivity to short-chain lipid (SCL)-conjugates. Together, our findings suggest that conjugation of small molecules with MCLs could be a powerful strategy for the design of probes and drugs.


Asunto(s)
Productos Biológicos , Proteínas de la Membrana , Productos Biológicos/metabolismo , Membrana Celular/metabolismo , Lípidos/química , Proteínas de la Membrana/química , Permeabilidad
2.
BJU Int ; 108(2): 241-7, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-20950307

RESUMEN

OBJECTIVE: • To evaluate the impact of urisheaths vs absorbent products (APs) on quality of life (QoL) in men with moderate to severe urinary incontinence (UI). PATIENTS AND METHODS: • A randomized, controlled, crossover trial in 61 outpatient adult men with stable, moderate to severe UI, with no concomitant faecal incontinence, was conducted from June 2007 to February 2009 in 14 urology centres. • Participants tested Conveen Optima urisheaths (Coloplast, Humlebaek, Denmark) with collecting bags and their usual AP in random order for 2 weeks each. • The impact of each on QoL was measured using the King's Health Questionnaire (KHQ) and the short form-12 acute questionnaire, and each patient's preference was recorded. • A 10-item patient questionnaire was also used to assess the product main advantages on an 11-point scale (0: worst; 10: best). A 72-h leakage diary was used to record the number and severity of leaks and daily product consumption. Safety was measured as the number of local adverse events. RESULTS: • All dimensions of the KHQ were scored lower with urisheaths, indicating an improvement in QoL. The greatest mean score reductions were in Limitations of Daily Activities (-10.24, P= 0.01) and Incontinence Impact (-7.05, P= 0.045). • The majority (69%) of patients preferred Conveen Optima urisheaths to their usual AP (P = 0.002). • Urisheaths scored significantly higher for all categories in the patient questionnaire (efficacy, self-image, odour management, discretion, skin integrity) except ease of use. • Safety was considered to be good. CONCLUSIONS: • Conveen Optima urisheaths showed a positive impact on QoL (according to the KHQ results) in moderate to severe incontinent men, who were long-term users of APs, and participants largely preferred urisheaths. • Conveen Optima urisheaths should be recommended to incontinent men in preference to APs.


Asunto(s)
Pañales para la Incontinencia , Prioridad del Paciente , Calidad de Vida , Incontinencia Urinaria , Urología/instrumentación , Anciano , Métodos Epidemiológicos , Humanos , Masculino , Persona de Mediana Edad
3.
Urol Res ; 37(4): 237-9, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19513704

RESUMEN

Clinical results in urinary stones management are often reported using the stone-free (SF) rate, which is simple, reproducible and useful to compare techniques or centers. But this index does not take into account costs or patients' quality of life. In a way, SF "pursuit", which cannot be considered as a universal therapeutic goal could increase costs and decrease patients' comfort. We retrospectively reviewed files of stone management to describe costs according to several items and we emphasize the need for a true efficiency index.


Asunto(s)
Cálculos Renales/terapia , Cálculos Urinarios/terapia , Urolitiasis/terapia , Costos de la Atención en Salud , Humanos , Cálculos Renales/economía , Tiempo de Internación , Calidad de Vida , Estudios Retrospectivos , Resultado del Tratamiento , Cálculos Urinarios/economía , Urolitiasis/economía
4.
Nephrol Dial Transplant ; 23(7): 2374-80, 2008 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-18283085

RESUMEN

BACKGROUND: We conducted a retrospective multi-centre study to determine the characteristics of prostate cancer in renal transplant recipients (RTR) and to analyse the relation with immunosuppressive maintenance therapies. METHODS: Patients from 19 French transplant centres diagnosed with prostate cancer at least 1 year after kidney transplantation were included in this study. Data regarding demographics, kidney transplantation, prostate cancer and immunosuppressive treatment were analysed. RESULTS: Sixty-two patients met the eligibility criteria for this study. Thirty-eight patients (61.3%) received calcineurin inhibitors (CNI) and azathioprine (AZA) with or without steroids, twenty received CNI with or without steroids (32.2%) and four received CNI and mycophenolate mofetil (6.5%). Patients with CNI and AZA immunosuppressive therapy presented more high-stage cancer (T3 and T4) when compared to patients receiving CNI alone (47.5% versus 15%, respectively, P = 0.03). A non-significant increase in lymph node invasion was found in patients receiving CNI and AZA compared to patients receiving CNI alone (21% versus 5%, P = 0.16). In the multivariate analysis, the immunosuppressive regimen with CNI and AZA was the only independent risk factor for locally advanced disease (P = 0.007). CONCLUSION: Our results showed that RTR are at risk for early occurrence and for locally advanced prostate cancer, especially when they received a CNI and AZA maintenance immunosuppressive therapy.


Asunto(s)
Inmunosupresores/uso terapéutico , Trasplante de Riñón , Neoplasias de la Próstata/epidemiología , Anciano , Azatioprina/uso terapéutico , Inhibidores de la Calcineurina , Francia/epidemiología , Humanos , Masculino , Tamizaje Masivo , Persona de Mediana Edad , Análisis Multivariante , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapéutico , Neoplasias de la Próstata/diagnóstico , Neoplasias de la Próstata/inmunología , Estudios Retrospectivos , Factores de Riesgo
5.
Prog Urol ; 17(4): 794-5, 2007 Jun.
Artículo en Francés | MEDLINE | ID: mdl-17633988

RESUMEN

There are six described complications of sickle cell trait or disease : gross hematuria, renal infarction, papillary necrosis, nephrotic syndrome and urine concentration defects. Because of a high frequency of sickle cell trait patients among patients suffering from medullary kidney carcinoma, it has been called the seventh complication. We briefly review physiopatholgy and diagnosis of these complications.


Asunto(s)
Anemia de Células Falciformes/complicaciones , Enfermedades Renales/etiología , Humanos
6.
Prog Urol ; 17(4): 828-31, 2007 Jun.
Artículo en Francés | MEDLINE | ID: mdl-17633995

RESUMEN

UNLABELLED: Cancer in a brain-dead subject constitutes a contraindication to organ harvesting. However no data are available on prostatic assessment of brain-dead subjects prior to organ harvesting. The objective of this study was to evaluate prostate cancer screening by serum PSA assay in potential organ donors over the age of 50. METHODS: From February to May 2006, serum PSA assays were performed in all male donors in 5 different organ harvesting centres. The donor's age and the duration of bladder catheterization were also recorded. RESULTS: Of the 85 organ harvests performed, 30 (35.3%) concerned men over the age of 50 years (mean: 60.4 years, range: 50-82 years). The mean duration of catheterization was 3.1 days (range: 0.5-22 days). The mean PSA level was 8.7 ng/ml (range: 0.03-52.7) with a free PSA/total PSA ratio of 31% (range: 14-47). Twelve donors had a PSA level greater than 4 ng/ml (4.7 to 52 ng/ml), two others had a PSA level greater than 2.5 ng/ml (2.77 and 3.3 in subjects aged 72 and 57 years, respectively). There was no correlation between the donor's age, their PSA level and the duration of catheterization. CONCLUSION: The age of brain-dead donors is increasing and is reaching the age limit recommended by the Association Francaise d'Urologie for prostate cancer screening by digital rectal examination and PSA assay. Although the risk of transmission of prostate cancer after transplantation is currently unknown, at this stage when the majority of prostate cancers are discovered in a context of elevated PSA with normal digital rectal examination, the risk of transmission of a prostate cancer from the donor to the recipient is minimal or even non-existent. Digital rectal examination findings may be more relevant than PSA to contraindicate organ harvesting.


Asunto(s)
Muerte Encefálica/sangre , Antígeno Prostático Específico/sangre , Neoplasias de la Próstata , Donantes de Tejidos , Recolección de Tejidos y Órganos , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo
7.
Prog Urol ; 17(7): 1382-4, 2007 Nov.
Artículo en Francés | MEDLINE | ID: mdl-18271428

RESUMEN

Amyloidosis of the seminal vesicles is a rare cause of haemospermia. The authors report the case of a 42-year-old patient with recurrent haemospermia over a period of 2 years and abnormalities of one seminal vesicle on ultrasonography and MRI, justifying laparoscopic resection. Histological examination demonstrated localized amyloidosis, secondary to inflammation. No recurrence was observed with a follow-up of one.


Asunto(s)
Amiloidosis/complicaciones , Amiloidosis/cirugía , Enfermedades de los Genitales Masculinos/complicaciones , Enfermedades de los Genitales Masculinos/cirugía , Hematospermia/etiología , Laparoscopía , Vesículas Seminales/cirugía , Adulto , Humanos , Masculino , Procedimientos Quirúrgicos Urológicos Masculinos/métodos
8.
Prog Urol ; 17(4): 832-5, 2007 Jun.
Artículo en Francés | MEDLINE | ID: mdl-17633996

RESUMEN

OBJECTIVE: To evaluate the proportion of surgical workload, in terms of time and number of procedures, devoted to chronic renal failure surgery in an urology and transplantation operating room. MATERIAL AND METHODS: Analysis of the operative activity of the urology and transplantation operating room of Amiens Hospital over a period of one year (2003), by evaluating the number of procedures and the operating room occupation time (time between entry and exit from the operating room) recorded on ecology forms completed for each operation. Procedures performed in this operating room comprise conventional adult urological surgery and chronic renal failure procedures (from creation of venous access sites for haemodialysis to treatment of complications of renal transplantation). RESULTS: Surgical management of chronic renal failure in the operating room represents 22.6% of all procedures and 30.1% of the operating room occupation time. 69% of the renal transplantation operating time and 95% of kidney harvesting operating time are performed on an oncall basis. CONCLUSION: Operative activity related to chronic renal failure represents almost one third of the total surgical workload of a department managing this disease. These data justify the allocation of additional surgical resources adapted to this activity that is growing in parallel to the number of patients with chronic renal failure.


Asunto(s)
Fallo Renal Crónico/cirugía , Trasplante de Riñón/estadística & datos numéricos , Quirófanos/estadística & datos numéricos , Procedimientos Quirúrgicos Urológicos/estadística & datos numéricos , Carga de Trabajo/estadística & datos numéricos , Humanos , Estudios Retrospectivos
9.
Prog Urol ; 17(1): 54-9, 2007 Feb.
Artículo en Francés | MEDLINE | ID: mdl-17373238

RESUMEN

STUDY OBJECTIVE: The objective of this prospective study was to describe the nature of the lesions observed during brain-dead cadavre donor kidney harvesting in France and to identify the risk factors for these lesions. MATERIAL AND METHODS: A questionnaire elaborated by the AFU Transplantation Committee concerning the quality of kidneys harvested from cadavre donors was sent to all centres performing renal transplantation in France in 2000. This prospective study was conducted over a period of 1 year and concerned the overall multi-organ harvesting procedure based on all data concerning the renal parenchyma, arteriovenous and ureteric characteristics, and the outcome of the transplants. RESULTS: Twelve centres completed the survey, allowing analysis of the data of 201 donor kidneys. 91% of harvesting surgeons were urologists. Various incidents were reported during 11% of harvesting procedures, but 1/3 of the abnormalities were not recorded by the harvesting surgeon. Isolated kidney harvesting was found to be a risk factor (20% vs 8.6%). The rate of parenchymal abnormalities was 50%, 2/3 of which were related to inadequate removal of perirenal fat. Atheroma was a risk factor for arterial lesions during harvesting (21% vs 6.50). Venous abnormalities were detected in 9% of cases: 89% of them were due to the harvesting procedure and 59% of them were not identified by the harvesting surgeon. The fact of not being a transplant surgeon was a risk factor for venous lesions (21.9% vs 6.5%). 4% of ureteric lesions were observed with no consequence on graft outcome. CONCLUSION: Adequate removal of perirenal fat before conditioning is not acquired. Isolated kidney harvesting and atheroma were risk factors for parenchymal and arterial lesions, respectively. Venous harvesting anomalies were more frequent among non-transplant surgeons.


Asunto(s)
Trasplante de Riñón/normas , Francia , Humanos , Estudios Prospectivos , Control de Calidad , Encuestas y Cuestionarios
10.
Eur Urol ; 71(2): 267-273, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27720531

RESUMEN

BACKGROUND: Up to a third of patients with localized prostate cancer have unilateral disease that may be suitable for partial treatment with hemiablation. OBJECTIVE: To evaluate the ability of high intensity focused ultrasound (HIFU) to achieve local control of the tumor in patients with unilateral localized prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: The French Urological Association initiated a prospective IDEAL multi-institutional study (2009-2015), to evaluate HIFU-hemiablation as a primary treatment. INTERVENTION: Multiparametric magnetic resonance imaging and biopsy were used for unilateral cancer diagnosis and control, and HIFU-hemiablation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary: absence of clinically significant cancer (CSC) on control biopsy at 1 yr (CSC: Gleason score ≥ 7 or cancer core length>3mm regardless of grade or > 2 positive cores). Secondary: presence of any cancer on biopsy, biochemical response, radical treatment free survival, adverse events, continence (no pad), erectile function (International Index of Erectile Function-5 ≥ 16), and quality of life (European Organization for Research and Treatment of Cancer QLQ-C28) questionnaires. RESULTS AND LIMITATIONS: One hundred and eleven patients were treated (mean age: 64.8 yr [standard deviation 6.2]; mean prostate-specific antigen: 6.2 ng/ml [standard deviation 2.6]; 68% low risk, 32% intermediate risk). Of the 101 patients with control biopsy, 96 (95%) and 94 (93%) had no CSC in the treated and contralateral lobes, respectively. Mean prostate-specific antigen at 2 yr was 2.3 ng/ml (standard deviation 1.7). The radical treatment-free survival rate at 2 years was 89% (radical treatments: six radical prostatectomies, three radiotherapies, and two HIFU). Adverse events were Grade 3 in 13%. At 12 mo continence and erectile functions were preserved in 97% and 78%. No significant decrease in quality of life score was observed at 12 mo. One limitation is the number of low-risk patients included in this study. CONCLUSIONS: At 1 yr, HIFU-hemiablation was efficient with 95% absence of clinically significant cancer associated with low morbidity and preservation of quality of life. Radical treatment-free survival rate was 89% at 2 yr. PATIENT SUMMARY: This report shows that high intensity focused ultrasound half-gland treatment of unilateral prostate cancer provides promising results with high cancer control and low morbidity.


Asunto(s)
Próstata/cirugía , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Ultrasonido Enfocado Transrectal de Alta Intensidad , Anciano , Humanos , Biopsia Guiada por Imagen , Imagen por Resonancia Magnética , Imagen por Resonancia Magnética Intervencional , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Próstata/diagnóstico por imagen , Neoplasias de la Próstata/diagnóstico por imagen , Resultado del Tratamiento
11.
Prog Urol ; 16(3): 343-6, 2006 Jun.
Artículo en Francés | MEDLINE | ID: mdl-16821348

RESUMEN

OBJECTIVE: To study the prevalence, treatment and outcome of urothelial bladder tumours (UBT) in renal transplant recipients. PATIENTS AND METHODS: Multicentre retrospective study performed in 2004 by questionnaire sent to members of the AFU Transplantation Committee. RESULT: Seven centres returned the questionnaire with a total of 32 UBTs in 21 males and 3 females with a mean age of 63.2 +/- 10.1 years, with no history of UBT. The incidence was 255 per 100,000. The median interval between transplantation and UBT was 60 months (range: 5 to 259 months). 72% of UBTs were stage pT > or = 1 and 63% were grade 3. CIS was present in 20% of cases. 25% of patients were N+. In addition to resection of the UBT, 3 patients were also treated with mitomycin C and 1 was treated with BCG. 7 patients underwent cystectomy, with a palliative objective in 42% of cases, associated with radiotherapy-chemotherapy (2/3) or chemotherapy alone (1/3). Immunosuppressive therapy was decreased in 50% of cases. Six patients (25%) died from bladder cancer, 25% relapsed with a tumour progression rate of 50%. 46% of patients were in remission of their UBT 4% died from an intercurrent cause. 76% of survivors have a Junctional graft with no alteration of serum creatinine. CONCLUSION: Renal transplant recipients have an increased incidence of UBT, which are more aggressive and associated with a higher mortality compared to the general population. Increased surveillance and aggressive treatment therefore appear to be justified.


Asunto(s)
Trasplante de Riñón , Complicaciones Posoperatorias , Neoplasias de la Vejiga Urinaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/terapia , Estudios Retrospectivos , Encuestas y Cuestionarios , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/terapia
12.
Prog Urol ; 16(1): 62-6, 2006 Feb.
Artículo en Francés | MEDLINE | ID: mdl-16526542

RESUMEN

INTRODUCTION: Prospective study of urodynamic changes induced by transobturator insertion of suburethral tape a dip-stick under-urethral. MATERIALS AND METHODS: 25 women with pure (12) or mixed (13) stress urinary incontinence were operated by this technique, allowing urodynamic assessment and completion of the MHU urinary disability questionnaire. Three operators performed these 25 tape insertions in 2 centres (Amiens and St Quentin hospitals) according to a standardized technique. Six months after the operation, patients were reviewed by clinical examination, MHU questionnaire and urodynamic assessment. RESULTS: The cure rate at 6 months was 80% (20 patients) and the improvement rate was 20% (5 patients). The maximum flow rate decreased from 23.6 ml/s to 18.9 ml/s (p = 0.02) and the post-voiding residual volume increased from 26.8 ml to 66.8 ml (p = 0.01). Urethral resistance increased from 0.16 to. 0.25 (p = 0.03) and maximum closure pressure increased from 43.8 to 47.5 cm H2O (p = 0.02). These results demonstrate the obstructive nature of this suburethral tape. The results of the MHU questionnaire showed accentuation of dysuria (p = 0.04) and improvement of stress urinary incontinence (p < 0.001). CONCLUSION: This prospective study confirms the efficacy of this technique, but analysis of the urodynamic studies and the MHU questionnaire demonstrates obstruction. Long-term surveillance of these patients by uroflowmetry and residual urine appears to be useful to detect possible progression to chronic urinary retention.


Asunto(s)
Prótesis e Implantes , Incontinencia Urinaria de Esfuerzo/cirugía , Urodinámica , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Uretra , Procedimientos Quirúrgicos Urológicos/métodos
13.
J Neurosci ; 24(33): 7335-43, 2004 Aug 18.
Artículo en Inglés | MEDLINE | ID: mdl-15317859

RESUMEN

Direction-selective retinal ganglion cells show an increased activity evoked by light stimuli moving in the preferred direction. This selectivity is governed by direction-selective inhibition from starburst amacrine cells occurring during stimulus movement in the opposite or null direction. To understand the intrinsic membrane properties of starburst cells responsible for direction-selective GABA release, we performed whole-cell recordings from starburst cells in mouse retina. Voltage-clamp recordings revealed prominent voltage-dependent K(+) currents. The currents were mostly blocked by 1 mm TEA, activated rapidly at voltages more positive than -20 mV, and deactivated quickly, properties reminiscent of the currents carried by the Kv3 subfamily of K+ channels. Immunoblots confirmed the presence of Kv3.1 and Kv3.2 proteins in retina and immunohistochemistry revealed their expression in starburst cell somata and dendrites. The Kv3-like current in starburst cells was absent in Kv3.1-Kv3.2 knock-out mice. Current-clamp recordings showed that the fast activation of the Kv3 channels provides a voltage-dependent shunt that limits depolarization of the soma to potentials more positive than -20 mV. This provides a mechanism likely to contribute to the electrical isolation of individual starburst cell dendrites, a property thought essential for direction selectivity. This function of Kv3 channels differs from that in other neurons where they facilitate high-frequency repetitive firing. Moreover, we found a gradient in the intensity of Kv3.1b immunolabeling favoring proximal regions of starburst cells. We hypothesize that this Kv3 channel gradient contributes to the preference for centrifugal signal flow in dendrites underlying direction-selective GABA release from starburst amacrine cells


Asunto(s)
Células Amacrinas/fisiología , Neuropéptidos/fisiología , Canales de Potasio con Entrada de Voltaje , Canales de Potasio/fisiología , Células Amacrinas/metabolismo , Animales , Conductividad Eléctrica , Ratones , Ratones Noqueados , Neuropéptidos/análisis , Neuropéptidos/genética , Técnicas de Placa-Clamp , Canales de Potasio/análisis , Canales de Potasio/genética , Retina/química , Retina/metabolismo , Canales de Potasio Shaw , Transmisión Sináptica
14.
J Gen Physiol ; 106(3): 393-414, 1995 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8786340

RESUMEN

We previously showed (Frace, A.M. and H.C. Hartzell. 1993. Journal of Physiology. 472:305-326) that internal perfusion of frog atrial myocytes with the nonselective protein phosphatase inhibitors microcystin or okadaic acid produced an increase in the L-type Ca current (ICa) and a decrease in the delayed rectifier K current (IK). We hypothesized that microcystin revealed the activity of a protein kinase (PKX) that was basally active in the cardiac myocyte that could phosphorylate the Ca and K channels or regulators of the channels. The present studies were aimed at determining the nature of PKX and its phosphorylation target. The effect of internal perfusion with microcystin on ICa or IK was not attenuated by inhibitors of protein kinase A (PKA). However, the effect of microcystin on ICa was largely blocked by the nonselective protein kinase inhibitors staurosporine (10-30 nM), K252a (250 nM), and H-7 (10 microM). Staurosporine and H-7 also decreased the stimulation of ICa by isoproterenol, but K252a was more selective and blocked the ability of microcystin to stimulate ICa without significantly reducing isoproterenol-stimulated current. Internal perfusion with selective inhibitors of protein kinase C (PKC), including the autoinhibitory pseudosubstrate PKC peptide (PKC(19-31)) and a myristoylated derivative of this peptide had no effect. External application of several PKC inhibitors had negative side effects that prevented their use as selective PKC inhibitors. Nevertheless, we conclude that PKX is not PKC. PKA and PKX phosphorylate sites with different sensitivities to the phosphatase inhibitors calyculin A and microcystin. In contrast to the results with ICa, the effect of microcystin on IK was not blocked by any of the kinase inhibitors tested, suggesting that the effect of microcystin on IK may not be mediated by a protein kinase but may be due to a direct effect of microcystin on the IK channel.


Asunto(s)
Canales de Calcio/efectos de los fármacos , Proteínas Quinasas Dependientes de AMP Cíclico/farmacología , Inhibidores Enzimáticos/farmacología , Corazón/efectos de los fármacos , Proteínas Quinasas/efectos de los fármacos , Animales , Microcistinas , Péptidos Cíclicos/farmacología , Rana esculenta , Factores de Tiempo
15.
J Gen Physiol ; 114(5): 673-84, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10532964

RESUMEN

Native and recombinant G protein-gated inwardly rectifying potassium (GIRK) channels are directly activated by the betagamma subunits of GTP-binding (G) proteins. The presence of phosphatidylinositol-bis-phosphate (PIP(2)) is required for G protein activation. Formation (via hydrolysis of ATP) of endogenous PIP(2) or application of exogenous PIP(2) increases the mean open time of GIRK channels and sensitizes them to gating by internal Na(+) ions. In the present study, we show that the activity of ATP- or PIP(2)-modified channels could also be stimulated by intracellular Mg(2+) ions. In addition, Mg(2+) ions reduced the single-channel conductance of GIRK channels, independently of their gating ability. Both Na(+) and Mg(2+) ions exert their gating effects independently of each other or of the activation by the G(betagamma) subunits. At high levels of PIP(2), synergistic interactions among Na(+), Mg(2+), and G(betagamma) subunits resulted in severalfold stimulated levels of channel activity. Changes in ionic concentrations and/or G protein subunits in the local environment of these K(+) channels could provide a rapid amplification mechanism for generation of graded activity, thereby adjusting the level of excitability of the cells.


Asunto(s)
Subunidades beta de la Proteína de Unión al GTP , Subunidades gamma de la Proteína de Unión al GTP , Proteínas de Unión al GTP/farmacología , Proteínas de Unión al GTP Heterotriméricas , Activación del Canal Iónico/efectos de los fármacos , Magnesio/farmacología , Canales de Potasio de Rectificación Interna , Canales de Potasio/fisiología , Sodio/farmacología , Adenosina Trifosfato/farmacología , Animales , Sitios de Unión/fisiología , Embrión de Pollo , Sinergismo Farmacológico , Conductividad Eléctrica , Canales de Potasio Rectificados Internamente Asociados a la Proteína G , Guanosina 5'-O-(3-Tiotrifosfato)/farmacología , Atrios Cardíacos/química , Atrios Cardíacos/citología , Activación del Canal Iónico/fisiología , Potenciales de la Membrana/fisiología , Miocardio/química , Miocardio/citología , Oocitos/fisiología , Técnicas de Placa-Clamp , Fosfatidilinositol 4,5-Difosfato/farmacología , Canales de Potasio/química , Xenopus
16.
Transplantation ; 75(2): 237-9, 2003 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-12548131

RESUMEN

BACKGROUND: There is no consensus regarding prostate cancer in renal-transplant recipients (RTR). A questionnaire evaluating prostate cancer screening after transplantation and assessing the number, diagnostic modalities, treatment, and outcome of prostate cancer cases was mailed to 22 French renal-transplant centers. RESULTS: Among 1,680 RTR in 1998, 11 (0.65%) cases of prostate cancer were diagnosed, and among the 2,338 recipients followed up, 28 (1%) cases of prostate cancer have been diagnosed and treated. Median ages at diagnosis and at transplantation were 63 and 58, respectively. Clinical stages were T1 50% and T2 25%. Eighteen patients had a Gleason score under 7. At 18 months of mean follow-up, 2 men had died from prostate cancer, and in the curative treatment group, 16 of 17 men were alive with no evidence of disease. CONCLUSIONS: The incidence of prostate cancer in RTR appeared to be higher than expected. Prostate specific antigen (PSA) testing should be performed routinely each year in renal transplantation centers.


Asunto(s)
Trasplante de Riñón/efectos adversos , Neoplasias de la Próstata/epidemiología , Adulto , Factores de Edad , Anciano , Humanos , Terapia de Inmunosupresión/efectos adversos , Incidencia , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/etiología
17.
J Med Microbiol ; 53(Pt 10): 985-990, 2004 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-15358820

RESUMEN

Three specimens from 111 asymptomatic male partners of infertile couples attending the Department of Urology in Amiens, France, were examined by the PCR COBAS AMPLICOR test (Roche Molecular Diagnostics) for the presence of Chlamydia trachomatis. The specimens analysed were: first void urine (FVU), urine obtained after prostatic massage (UPM) and semen specimens. Serum from each patient was also obtained and analysed for the presence of IgG and IgA chlamydial antibodies by in-house microimmunofluorescence (MIF) and pELISA. C. trachomatis was detected by PCR in 5.4% of FVU samples, 2.7% of semen specimens and in 0.9% of UPM samples. Two treatments for processing the samples (storage at -70 degrees C and heating to 95 degrees C) were routinely used before initial testing to reduce the effects of inhibitors of PCR. Despite these precautions, the PCR method revealed the presence of inhibitors in 7.3% of semen specimens and 3.6% of FVU samples. C. trachomatis was detected by PCR COBAS AMPLICOR in seven of 111 patients (6.3%) and by serology in five of 111 patients (4.5%). The detection of C. trachomatis in FVU, UPM and semen specimens can serve as a marker for the presence of this organism in the genital tract, and can be used as a reliable way of detecting asymptomatic carriers of infection.


Asunto(s)
Infecciones por Chlamydia/epidemiología , Chlamydia trachomatis/aislamiento & purificación , Infertilidad Masculina/microbiología , Adulto , Anticuerpos Antibacterianos/sangre , ADN Bacteriano/análisis , Humanos , Masculino , Reacción en Cadena de la Polimerasa , Semen/microbiología , Orina/microbiología
18.
Prog Urol ; 12(6): 1294-6, 2002 Dec.
Artículo en Francés | MEDLINE | ID: mdl-12545643

RESUMEN

The authors report the case of a patient with multiple urothelial tumours only sparing the superior left ureter and the urethra. The complex treatment consisted of a combination of resection of the entire urinary tract, except for the left kidney and its proximal ureter that was transplanted into the right iliac fossa, after ex vivo partial pyelectomy. This complex treatment regimen avoided the need for dialysis with a good functional and oncological result, three years later.


Asunto(s)
Carcinoma de Células Renales/cirugía , Trasplante de Riñón , Neoplasias Primarias Múltiples/cirugía , Neoplasias Urológicas/cirugía , Humanos , Masculino , Persona de Mediana Edad
19.
Prog Urol ; 12(2): 318-20, 2002 Apr.
Artículo en Francés | MEDLINE | ID: mdl-12108352

RESUMEN

Lympoepithelioma, originally described within the nasopharynx is an undifferenciated malignant epithelial tumor with a prominent lymphoid stroma. We report a case of lymphoepithelioma of the bladder after intravesical BCG treatment for carcinoma in situ.


Asunto(s)
Carcinoma/patología , Neoplasias de la Vejiga Urinaria/patología , Vacuna BCG/uso terapéutico , Carcinoma in Situ/tratamiento farmacológico , Carcinoma in Situ/patología , Humanos , Masculino , Persona de Mediana Edad
20.
Prog Urol ; 14(1): 87-9, 2004 Feb.
Artículo en Francés | MEDLINE | ID: mdl-15098763

RESUMEN

Emphysematous cystitis is a rare disease mainly encountered in poorly controlled diabetics, immunodepressed patients or patients with infravesical obstruction. The pathophysiology of this disease is characterized by the formation of carbon dioxide (CO2) present in the lumen and/or bladder wall, derived from bacterial fermentation of carbohydrates. The bacteria most frequently responsible are facultative aerobes-anaerobes (Escherichia coli) and more rarely strict anaerobes (Clostridium perfringens). The authors report a case of emphysematous cystitis in a context of pelvic trauma and fracture of the pelvis, complicated by secondary bladder rupture. The diagnostic and therapeutic aspects are discussed.


Asunto(s)
Cistitis/complicaciones , Enfisema/complicaciones , Vejiga Urinaria/lesiones , Anciano , Cistitis/diagnóstico , Cistitis/cirugía , Enfisema/diagnóstico , Enfisema/cirugía , Femenino , Humanos , Enfermedades de la Vejiga Urinaria/complicaciones , Enfermedades de la Vejiga Urinaria/diagnóstico , Enfermedades de la Vejiga Urinaria/cirugía
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