Various surgical techniques for the repair of injured vas deferens in rat experiment Introduction: The herniotomy for inguinal hernia is one of the most frequent surgical procedures in paediatric surgery. The incidence of complication following primary inguinal herniotomy in neonates is not rare and repair of the injured vas deferens (VD) is not standardized. The aim of this experimental study was to assess the contusion of VD during the surgery with a surgical instrument and to perform and consequently analyze some possibilities of a simple repair method under the control of operating loupe. Methods: Seventy male rats were divided into seven subgroups according to the type of the vas deferens injury and its repair consequently: 1. Contusion, 2. cut-off and a simple one layer vasovasostomy sewn by absorbable sewing material, 3. cut-off and joining by an intraluminally lead fibre of absorbable sewing material knotted externally, 4. = 3. using non- absorbable sewing material, 5. = 2. combine with intraluminally situated absorbable sewing fibre fixed externally,6. = 5. combine with intraluminally situated non-absorbable sewing fibre fixed externally, 7. = 5. without external fixation. Fibres of non-absorbable sewing material were removed 3 weeks after the first operation. Operated or injured parts of...

Repeated exposure of the rat vas deferens to the imidazoline oxymetazoline (OXY) results in a progressive loss of response which can appear selective for imidazoline agonists. The present study tests the hypothesis that imidazolines produce desensitization through prolonged blockade or inactivation of alpha-1 adrenoreceptors. Repeated exposure to OXY, naphazoline (NPZ) or tetrahydrozoline (THZ) produces a concentration- and time-dependent rightward shift and depression of the (-)-epinephrine concentration-effect curve, suggesting a mechanism of prolonged receptor blockade or inactivation. (-)-Epinephrine Kd values were similar when estimated after either receptor inactivation with phenoxybenzamine or repeated exposure to imidazolines. The differences in the ability of individual imidazolines to produce desensitization (order of potency: OXY greater than NPZ greater than or equal to THZ) do not follow their intrinsic activity (NPZ approximately THZ approximately OXY) or affinity (OXY greater than or equal to NPZ greater than THZ). The ability of individual imidazoline and phenethylamine agonists to produce a response in imidazoline-desensitized rat vas deferens reflects agonist intrinsic efficacy. Desensitization by imidazoline exposure does not affect contraction produced by either KCl or neurokinin A. Imidazolines produce effects similar to receptor inactivation and their desensitization in vas deferens can be explained without invoking an imidazoline subtype of alpha-1 adrenoreceptor.

A Fibrose Cística (FC) é a doença autossômica recessiva mais freqüente em caucasianos e está associada, em seu amplo espectro de apresentação clínica, a mais de 1500 mutações no gene CFTR (Cystic Fibrosis Transmembrane conductance regulator). O papel de CFTR é especialmente relevante no desenvolvimento da porção reprodutiva dos ductos mesonéfricos. Em 98% dos pacientes masculinos portadores da FC, mutações em CFTR são responsáveis pela ausência bilateral congênita dos ductos deferentes (CBAVD), associada à anomalias variáveis das vesículas seminais, ductos ejaculatórios e da porção distal dos epidídimos. A ausência uni ou bilateral congênita dos ductos deferentes (CAVD), na ausência de outros sinais clínicos de FC, é conhecida causa de infertilidade masculina, presente em 1%-2% de todos os homens inférteis, e em cerca de 10% dos azoospérmicos. A reprodução assistida utilizando a injeção intracitoplasmática de espermatozóides (ICSI) obtidos preferencialmente por aspiração microcirurgica de espermatozóides do epidídimo (MESA) permite a paternidade biológica a esses pacientes. Em função da alta morbi-mortalidade da FC e da alta freqüência de portadores assintomáticos, estimada em 1:25, é recomendável que seja realizado teste para identificação de mutações em CFTR em todos os pacientes com CAVD antes de serem submetidos à ICSI. Em populações de etnia homogênea, a mutação F508 é identificada em 90% dos pacientes com FC e em 70% a 85% dos pacientes com CAVD. No Brasil, onde diferenças étnicas refletem a heterogeneidade genética, a freqüência da mutação F508 varia entre 23% e 50% em paciente com FC indicando que outras mutações devam estar envolvidas. Este dado levou ao estudo completo do gene CFTR de 20 homens inférteis com CAVD visando a identificação das mutações mais prevalentes em nossa população. Foram identificadas mutações em 17 pacientes (85%): três DF508 representando 15% (3/20), uma G542X, uma 875+1G>A e 4 mutações ainda não descritas na literatura, a S753R, G149W identificada em dois irmãos, V580F e a 712-1G>T. A variação no trato polipirimidínico em IVS8 (alelo 5T), seja como segunda mutação ou presente em homozigose, está diretamente relacionada com a CAVD, com freqüências em população caucasiana masculina infértil variando entre 21% e 30%. No presente estudo, 15 (15/20=75%) pacientes apresentaram o alelo a variante alélica 5T sendo que em 8 pacientes essa variante alélica foi identificada em heterozigose composta com outra mutação. Anomalias renais foram identificadas em 6 pacientes, todos com CBAVD. O presente estudo pode correlacionar o fenótipo da CAVD a alterações no genótipo de CFTR em 100% dos pacientes investigados / Cystic Fibrosis (CF) is the most common autosomal recessive disorder in caucasians and is associated, in an wide variety of different clinical manifestatons. More than 1500 mutations in the CFTR gene (Cystic Fibrosis regulator Transmembrane conductance) have been described and an even growing number of mutations are being currently studied worldwide. The role of CFTR gene is especially important in reproductive tissues of the mesonephric tract sensitive to the expression of the CFTR gene. The great majority of infertile males with CF (98%) have clinical manifestations and mutations in CFTR are responsible for the congenital bilateral absence of the vas deferens (CBAVD), associated to the abnormalities of the seminal vesicles, ejaculatory ducts and/or the distal portion of the epididymis. The congenital absence, uni or bilateral, of the vas deferens (CAVD), in the absence of other clinical signals of CF is a known cause of male infertility present in 1%-2% of all men investigated and in about 10% of men with obstructive azoospermia. Serious considerations should be drawn about the lack of proper diagnosis of infetile males with CFTR that seek reproductive clinics for assisted reproductive techniques (ARTs), as well as the lack of proper consideratins of the existance of this disease as a potential cause of male infetility among male are takers, like urologistas, andrologistas and gynecologists that rush for the misuse of ARTs. The introduction of Intracytoplasmic Sperm Injection (ICSI), has given new reproductive potetntial for these couples, but again as in the majority of cases it is obstructive azoospermia, couples should be advised about proper microsurgical sperm retrieval, preferentialy microsurgical epydidymal sperm aspiration (MESA). As a consequence of the potential high mortality rate of the CF descendents and the high frequency of carriers, estimated in 1:25,it is highly recommended that tests for correct identification of mutations in CFTR gene are carried out for all patients with CAVD before considered being submitted to ICSI. In populations of homogeneous ethnic origin, the mutation F508 is identified in 90% of the patients with CF and between 70% and 85% of the patients with CAVD. In Brazil, where ethnic differences reflect the genetic heterogeneity, the frequency of the mutation in F508 varies between 23% and 50%, indicating that other mutations must have a role. Our data looked carefully in the CFTR gene of 20 infertile men with CAVD aiming at the identification of the most prevalent mutations in our population. Mutations had been identified in 17 patients (85%): three DF508 representing 15% (3/20), one G542X, one 875+1G>A and 4 mutations not yet described in literature, S753R, G149W identified in two brothers, V580F and 712-1G>T. In the literature the allelic variant in IVS8 (allele 5T), either as a second mutation or in homozygosis, is directly related with the CAVD, with reported frequencies in the infertile caucasian male population varying between 21% and 30%. In the present study, 15 (15/20=75%) patients presented the CFTR mutation in the IVS8/5T: eight of them in heterozygosis composed with another mutation. Regarding genitourinary tract malformations, kidney anomalies were identified in 6 patients, all with CBAVD. In the present study we could correlationate the phenotype of the CAVD with the genotype alterations of CFTR gene in 100% of the investigated patients

A Fibrose Cística (FC) é a doença autossômica recessiva mais freqüente em caucasianos e está associada, em seu amplo espectro de apresentação clínica, a mais de 1500 mutações no gene CFTR (Cystic Fibrosis Transmembrane conductance regulator). O papel de CFTR é especialmente relevante no desenvolvimento da porção reprodutiva dos ductos mesonéfricos. Em 98% dos pacientes masculinos portadores da FC, mutações em CFTR são responsáveis pela ausência bilateral congênita dos ductos deferentes (CBAVD), associada à anomalias variáveis das vesículas seminais, ductos ejaculatórios e da porção distal dos epidídimos. A ausência uni ou bilateral congênita dos ductos deferentes (CAVD), na ausência de outros sinais clínicos de FC, é conhecida causa de infertilidade masculina, presente em 1%-2% de todos os homens inférteis, e em cerca de 10% dos azoospérmicos. A reprodução assistida utilizando a injeção intracitoplasmática de espermatozóides (ICSI) obtidos preferencialmente por aspiração microcirurgica de espermatozóides do epidídimo (MESA) permite a paternidade biológica a esses pacientes. Em função da alta morbi-mortalidade da FC e da alta freqüência de portadores assintomáticos, estimada em 1:25, é recomendável que seja realizado teste para identificação de mutações em CFTR em todos os pacientes com CAVD antes de serem submetidos à ICSI. Em populações de etnia homogênea, a mutação F508 é identificada em 90% dos pacientes com FC e em 70% a 85% dos pacientes com CAVD. No Brasil, onde diferenças étnicas refletem a heterogeneidade genética, a freqüência da mutação F508 varia entre 23% e 50% em paciente com FC indicando que outras mutações devam estar envolvidas. Este dado levou ao estudo completo do gene CFTR de 20 homens inférteis com CAVD visando a identificação das mutações mais prevalentes em nossa população. Foram identificadas mutações em 17 pacientes (85%): três DF508 representando 15% (3/20), uma G542X, uma 875+1G>A e 4 mutações ainda não descritas na literatura, a S753R, G149W identificada em dois irmãos, V580F e a 712-1G>T. A variação no trato polipirimidínico em IVS8 (alelo 5T), seja como segunda mutação ou presente em homozigose, está diretamente relacionada com a CAVD, com freqüências em população caucasiana masculina infértil variando entre 21% e 30%. No presente estudo, 15 (15/20=75%) pacientes apresentaram o alelo a variante alélica 5T sendo que em 8 pacientes essa variante alélica foi identificada em heterozigose composta com outra mutação. Anomalias renais foram identificadas em 6 pacientes, todos com CBAVD. O presente estudo pode correlacionar o fenótipo da CAVD a alterações no genótipo de CFTR em 100% dos pacientes investigados / Cystic Fibrosis (CF) is the most common autosomal recessive disorder in caucasians and is associated, in an wide variety of different clinical manifestatons. More than 1500 mutations in the CFTR gene (Cystic Fibrosis regulator Transmembrane conductance) have been described and an even growing number of mutations are being currently studied worldwide. The role of CFTR gene is especially important in reproductive tissues of the mesonephric tract sensitive to the expression of the CFTR gene. The great majority of infertile males with CF (98%) have clinical manifestations and mutations in CFTR are responsible for the congenital bilateral absence of the vas deferens (CBAVD), associated to the abnormalities of the seminal vesicles, ejaculatory ducts and/or the distal portion of the epididymis. The congenital absence, uni or bilateral, of the vas deferens (CAVD), in the absence of other clinical signals of CF is a known cause of male infertility present in 1%-2% of all men investigated and in about 10% of men with obstructive azoospermia. Serious considerations should be drawn about the lack of proper diagnosis of infetile males with CFTR that seek reproductive clinics for assisted reproductive techniques (ARTs), as well as the lack of proper consideratins of the existance of this disease as a potential cause of male infetility among male are takers, like urologistas, andrologistas and gynecologists that rush for the misuse of ARTs. The introduction of Intracytoplasmic Sperm Injection (ICSI), has given new reproductive potetntial for these couples, but again as in the majority of cases it is obstructive azoospermia, couples should be advised about proper microsurgical sperm retrieval, preferentialy microsurgical epydidymal sperm aspiration (MESA). As a consequence of the potential high mortality rate of the CF descendents and the high frequency of carriers, estimated in 1:25,it is highly recommended that tests for correct identification of mutations in CFTR gene are carried out for all patients with CAVD before considered being submitted to ICSI. In populations of homogeneous ethnic origin, the mutation F508 is identified in 90% of the patients with CF and between 70% and 85% of the patients with CAVD. In Brazil, where ethnic differences reflect the genetic heterogeneity, the frequency of the mutation in F508 varies between 23% and 50%, indicating that other mutations must have a role. Our data looked carefully in the CFTR gene of 20 infertile men with CAVD aiming at the identification of the most prevalent mutations in our population. Mutations had been identified in 17 patients (85%): three DF508 representing 15% (3/20), one G542X, one 875+1G>A and 4 mutations not yet described in literature, S753R, G149W identified in two brothers, V580F and 712-1G>T. In the literature the allelic variant in IVS8 (allele 5T), either as a second mutation or in homozygosis, is directly related with the CAVD, with reported frequencies in the infertile caucasian male population varying between 21% and 30%. In the present study, 15 (15/20=75%) patients presented the CFTR mutation in the IVS8/5T: eight of them in heterozygosis composed with another mutation. Regarding genitourinary tract malformations, kidney anomalies were identified in 6 patients, all with CBAVD. In the present study we could correlationate the phenotype of the CAVD with the genotype alterations of CFTR gene in 100% of the investigated patients