The relaxation effect of endocannabinoid anandamide on isolated rat bladder and vas deferens tissues and possible mechanisms.

BACKGROUND: The endocannabinoid system plays important roles in various systems, including the genitourinary system; however, its mechanism of action is not fully understood. OBJECTIVES: This study aimed to investigate the direct relaxant effects of anandamide and its possible mechanisms in isolated rat bladder and vas deferens tissues. METHODS: Twenty-one adult male Wistar albino rats were used. Bladder and vas deferens (prostatic and epididymal portions) tissues were mounted in 10 mL of organ baths. Relaxation responses to anandamide were recorded at 3 and 10 µM concentrations. After the rest period, the procedures were repeated in the presence of cannabinoid (CB) and vanilloid receptor antagonists, various potassium channel blockers, cyclo-oxygenase, and nitric oxide synthase inhibitors. In different tissues to investigate the Ca2+-channel antagonistic effect of anandamide, concentration-response curves to CaCl2 were obtained in the absence and presence of anandamide. RESULTS: Anandamide caused a significant relaxation response in the bladder and epididymal vas deferens tissues, but not in the prostatic portion. The effect of anandamide was antagonized in the presence of the CB1 antagonist AM251 or the non-selective potassium channel blocker tetraethylammonium in bladder tissue. In the epididymal vas deferens, anandamide significantly inhibited the calcium contraction responses, especially at high concentrations. The CB2 antagonist AM630 reversed this inhibition. CONCLUSIONS: The results show that anandamide has a direct relaxant effect on the isolated rat bladder and epididymal vas deferens. Anandamide triggers different mechanisms in different types of tissues, and further studies are needed to elucidate the mechanism of action of anandamide.

What You Should Know About Vasitis: A Case Report.

Even though infected vasitis is rarely reported in the literature, there are other diagnoses that share the same clinical signs, including testicular torsion, epididymo-orchitis, epididymitis, trauma, and incarcerated hernia. A 27-year-old man was brought to the emergency department by his brother with right inguinal and testicular pain for one day. The history was not significant with fever, lower urinary tract symptoms, urethral discharge, change in bowel habits, previous history of inguinal swelling, or surgical intervention. On presentation, the patient was vitally stable, and right infra-inguinal and inguinal vas deferens were tender and swollen; however, both testes and epididymis were normal, and no urethral discharge. Vasitis, or inflammation of the vas deferens, is an uncommon illness that Chan PT and Schlegel classified as either asymptomatic vasitis nodosa or severely painful infectious vasitis. Acute infective vasitis is a really uncommon illness, with only a few occurrences documented in the literature. However, the retrograde transmission of urinary pathogens such as Escherichia coli and Haemophilus influenza is thought to cause acute vasitis. Because of its rarity and ambiguous imaging findings, diagnosing vasitis can be difficult. Epididymitis, orchitis, and testicular torsion can all be ruled out with ultrasound and duplex Doppler screening. Inguinal hernia is difficult to distinguish from vasitis with ultrasound; hence, CT and MRI are more commonly used to confirm the diagnosis. Since this is the first occurrence in our city that we are aware of, it was reported. A few cases from Saudi Arabia have also been documented, and by doing so, we may raise clinicians' awareness of this disease and ensure that they can treat patients without making an incorrect diagnosis.

ECFS standards of care on CFTR-related disorders: Identification and care of the disorders.

This is the third paper in the series providing updated information and recommendations for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder (CFTR-RD). This paper covers the individual disorders, including the established conditions - congenital absence of the vas deferens (CAVD), diffuse bronchiectasis and chronic or acute recurrent pancreatitis - and also other conditions which might be considered a CFTR-RD, including allergic bronchopulmonary aspergillosis, chronic rhinosinusitis, primary sclerosing cholangitis and aquagenic wrinkling. The CFTR functional and genetic evidence in support of the condition being a CFTR-RD are discussed and guidance for reaching the diagnosis, including alternative conditions to consider and management recommendations, is provided. Gaps in our knowledge, particularly of the emerging conditions, and future areas of research, including the role of CFTR modulators, are highlighted.

Cellular Distribution of Aquaporin 3, 7 and 9 in the Male Reproductive System: A Lesson from Bovine Study (Bos taurus).

The increasing incidence of male infertility in humans and animals creates the need to search for new factors that significantly affect the course of reproductive processes. Therefore, the aim of this study was to determine the temporospatial expression of aquaglyceroporins (AQP3, AQP7 and AQP9) in the bovine (Bos taurus) reproductive system using immunohistochemistry and Western blotting. The study also included morphological analysis and identification of GATA-4. In brief, in immature individuals, AQP3 and AQP7 were found in gonocytes. In reproductive bulls, AQP3 was observed in spermatocytes and spermatogonia, while AQP7 was visible in all germ cells and the Sertoli cells. AQP7 and AQP9 were detected in the Leydig cells. Along the entire epididymis of reproductive bulls, aquaglyceroporins were visible, among others, in basal cells (AQP3 and AQP7), in epididymal sperm (AQP7) and in the stereocilia of the principal cells (AQP9). In males of all ages, aquaglyceroporins were identified in the principal and basal cells of the vas deferens. An increase in the expression of AQP3 in the testis and cauda epididymis and a decrease in the abundance of AQP7 in the vas deferens with age were found. In conclusion, age-related changes in the expression and/or distribution patterns of AQP3, AQP7 and AQP9 indicate the involvement of these proteins in the normal development and course of male reproductive processes in cattle.

Regulation of nerve-evoked contractions of the murine vas deferens.

Stimulation of sympathetic nerves in the vas deferens yields biphasic contractions consisting of a rapid transient component resulting from activation of P2X1 receptors by ATP and a secondary sustained component mediated by activation of α1-adrenoceptors by noradrenaline. Noradrenaline can also potentiate the ATP-dependent contractions of the vas deferens, but the mechanisms underlying this effect are unclear. The purpose of the present study was to investigate the mechanisms underlying potentiation of transient contractions of the vas deferens induced by activation of α1-adrenoceptors. Contractions of the mouse vas deferens were induced by electric field stimulation (EFS). Delivery of brief (1s duration) pulses (4 Hz) yielded transient contractions that were inhibited tetrodotoxin (100 nM) and guanethidine (10 µM). α,ß-meATP (10 µM), a P2X1R desensitising agent, reduced the amplitude of these responses by 65% and prazosin (100 nM), an α1-adrenoceptor antagonist, decreased mean contraction amplitude by 69%. Stimulation of α1-adrenoceptors with phenylephrine (3 µM) enhanced EFS and ATP-induced contractions and these effects were mimicked by the phorbol ester PDBu (1 µM), which activates PKC. The PKC inhibitor GF109203X (1 µM) prevented the stimulatory effects of PDBu on ATP-induced contractions of the vas deferens but only reduced the stimulatory effects of phenylephrine by 40%. PDBu increased the amplitude of ATP-induced currents recorded from freshly isolated vas deferens myocytes and HEK-293 cells expressing human P2X1Rs by 93%. This study indicates that: (1) potentiation of ATP-evoked contractions of the mouse vas deferens by α1-adrenoceptor activation were not fully blocked by the PKC inhibitor GF109203X and (2) that the stimulatory effect of PKC on ATP-induced contractions of the vas deferens is associated with enhanced P2X1R currents in vas deferens myocytes.

Application of contrast-enhanced ultrasound in the diagnosis of tuberous vas deferens tuberculosis.

BACKGROUND: To assess the value of contrast-enhanced ultrasound (CEUS) in the diagnosis of tuberous vas deferens tuberculosis (VD TB) and improve the positive diagnostic rate of VD TB. METHODS: CEUS and routine ultrasound (US) images of 17 patients with tuberous VD TB confirmed by surgery, pathology, or laboratory semen examination were retrospectively analyzed and summarized, and the positive rates of both imaging techniques were compared. RESULTS: The 19 VD lesions of the 17 patients were divided into two types according to the CEUS findings: Type I and Type II, and type II was divided into Types IIa, IIb, and IIc. Of the nodules with transverse diameters > 1 cm, 100% presented as type II. Of the nodules with transverse diameters < 1 cm, 37.5% (3/8) presented as type I and 62.5% (5/8) presented as type II. The sonographic manifestations of tuberous VD TB were hypoechoic and mixed echoic. The positive diagnostic rate was 89.5% for CEUS and 68.4% for US, but the difference was not significant (χ2 = 2.533; P = 0.111). CONCLUSIONS: CEUS was able to show the blood supply characteristics of tuberous VD TB, the internal necrosis of nodules was more easily observed by CEUS than by routine US, which is helpful for the diagnosis of tuberous VD TB.

Preperitoneal vas deferens infiltration in high-risk prostate cancer.

Objectives: The objective of this study is to evaluate the prevalence and the importance of preperitoneal vas deferens (VD) infiltration in high-risk prostate cancer (PCa). Patients and Methods: In this prospectively designed study, we included 332 high-risk PCa patients with a Briganti score >5%, who were treated by robot-assisted radical prostatectomy between July 2017 and February 2022 at the Urology Department, SLK Kliniken Heilbronn. In addition to the standard histological analysis of the distal VD, which was attached to the prostate specimen, we analysed the infiltration status of preperitoneal VD in this cohort. The preperitoneal VD, which represents the middle part of ductus deferens and extends between the internal inguinal ring and obturator fossa, was resected during extended pelvic lymphadenectomy. Distal and preperitoneal VD status was registered together with preoperative and postoperative disease characteristics. Descriptive analysis methods and logistic regression analysis were used. Results: Briganti score of the target cohort had a median value of 19%, while 235 patients (70.8%) of the group demonstrated a locally advanced disease. The Grade Group at prostatectomy specimen was at least 3 for 286 patients (86.1%). Distal VD infiltration was found in 20 patients (6%) and preperitoneal VD infiltration in two patients (0.6%). Distal VD infiltration was not associated with an increased possibility for positive surgical margins or nodal status among pT3b patients, while both patients with preperitoneal VD infiltration were characterized by highly aggressive disease in locally advanced stage and bilateral distal VD infiltration. Conclusions: PCa extension along VD may reach a more proximal point of VD than the reported from the existing data infiltration of VD adjacent to seminal vesicles. This rare manifestation of PCa local extension may be the intermediate step to the rare cases of recurrence in the testicles. However, more robust data are needed to confirm the aforementioned hypothesis. Distal VD infiltration seems to have no additional prognostic value among patients with infiltrated seminal vesicles.

Compound heterozygous mutations in CFTR causing congenital bilateral absence of the vas deferens in a Chinese pedigree.

BACKGROUND: Cystic fibrosis (CF) is an autosomal recessive disorder rarely found in Asian populations. Most males with CF are infertile because of obstructive azoospermia (OA) caused by congenital bilateral absence of the vas deferens (CBAVD). Compound heterozygous mutations of cystic fibrosis transmembrane conductance regulator (CFTR) are among the most common pathogenic factors in CBAVD. However, few genealogical analyses have been performed. METHODS: In this study, whole-exome sequencing and cosegregation analysis were performed in a Chinese pedigree involving two siblings with CBAVD. Moreover, in vitro gene expressions were used to analyze the pathogenicity of a novel CFTR mutation. RESULTS: We identified compound heterozygous mutations of CFTR comprising the known disease-causing variant c.1210-11T>G (also known as IVS9-5 T) and c.2144delA;p.q715fs in two siblings with CBAVD. To verify the effects in vitro, we transfected vectors expressing wild-type and mutated CFTR into 293T cells. The results showed that the CFTR protein containing the frameshift mutation (c.2144delA) was 60 kD smaller. With testicular sperm aspiration/intracytoplasmic sperm injection-embryo transfer (TESA/ICSI-ET), both CBAVD patients fathered healthy offspring. CONCLUSION: Our study revealed that compound heterozygous mutations of CFTR are involved in CBAVD, expanding the known CFTR gene mutation spectrum of CBAVD patients and providing more evidence that compound heterozygous mutations can cause familial CBAVD.

What's in a name? Is an anatomical term only a name?

The purpose of a standard terminology is to facilitate communication. Thus, changing the name of an anatomical structure or the meaning of an anatomical term undermines that aspiration and cuts connections with anatomy's long history. Two types of anatomical terms are the most vulnerable to logical arguments for revision-ones that are descriptive, but viewed, at least by some, as inaccurate, and ones that contain words that are polysemic or vague. A half dozen examples of each type are discussed, including ductus deferens, glandula seminalis, articulationes costochondrales, vulva and fascia. In general, traditional terms should be preserved, but judgments about which terms are traditional should be based on five centuries of modern anatomy, not just the past several decades.

Assessment of copper nanoparticles treatment on male accessory reproductive organs and epididymis in a mouse model: A morphological and biochemical study.

Although the usage of nanoparticles has expanded substantially in recent years, and it causes the detrimental effect on the various organs. CuNPs are widely used in commercial applications. There has been minimal investigation into the possibly harmful effects of CuNPs on the accessory reproductive organs. Thus, the present study aimed to investigate the effect of CuNPs on the male reproductive organs like epididymis, vas deferens, seminal vesicle and prostate of mice. The mice were exposed orally to CuNPs at three doses 10, 100, and 200 mg/kg for 70 days. Our results showed that the organs index of only vas deferens and prostate reduced at 200 mg/kg group compared to the control. However, the histological study showed degenerative changes in the epididymis at higher doses like distortion in the tubules. The sperm parameters were also decreased in the 200 mg/kg CuNPs group. The vas deferens in 100 and 200 mg/kg treatment groups exhibited detachment of luminal epithelium and with a few or no spermatozoa in the higher dose group. The seminal vesicle and prostate also showed degenerative changes like atrophy, hyperplasia, and scant secretary materials. Furthermore, CuNPs also increased the oxidative stress and decreased antioxidant enzymes in vas deferens and seminal vesicles at higher dose. Caput epididymis showed decreased GPx enzymes in all the groups. However, MDA and GPx in corpus, cauda, and prostate did not show any significant variations among all the groups. In conclusion, our results suggest that CuNPs can manifest the detrimental effect of the male accessory organs and epididymis in a dose and tissue dependent manner. Since, detrimental effects were observed only at higher dose, thus, uses of CuNPs would be safe for reproductive organs at lower dose, even for the prolonged duration.

Spermatic vein thrombosis as a rare cause of testicular pain - review of the literature.

Introduction: The authors in this paper discuss a rare disease entity that can cause testicular pain and mimic varicocele. Material and methods: Citing data from a review of the world literature, spermatic cord thrombosis is most often misdiagnosed as an incarcerated inguinal hernia. Patients usually complain of pain and swelling of the testicle, pain in the inguinal region, and sometimes a palpable mass in the inguinal region. Results: Ultrasonography with colour Doppler usually establishes the correct diagnosis. Currently, there are no official recommendations for the treatment of this disease.There are reports of conservative treatment of spermatic cord thrombosis in the world literature. However, it seems that the gold standard of management remains surgical exploration, which allows us to unequivocally establish the correct diagnosis. In cases of co-morbid thrombosis with spermatic cord varicocelectomy is recommended. Conclusions: Due to the rarity of this disease, the topic of this article was undertaken. The paper reviews the world literature relating to the diagnosis and treatment of this disease entity. Our own algorithm for the management of spermatic cord thrombosis is proposed.

Male contraception: narrative review of ongoing research.

BACKGROUND: Since the release of the combined oral contraceptive pill in 1960, women have shouldered the burden of contraception and family planning. Over 60 years later, this is still the case as the only practical, effective contraceptive options available to men are condoms and vasectomy. However, there are now a variety of promising hormonal and non-hormonal male contraceptive options being studied. The purpose of this narrative review is to provide clinicians and laypeople with focused, up-to-date descriptions of novel strategies and targets for male contraception. We include a cautiously optimistic discussion of benefits and potential drawbacks, highlighting several methods in preclinical and clinical stages of development. RESULTS: As of June 2023, two hormonal male contraceptive methods are undergoing phase II clinical trials for safety and efficacy. A large-scale, international phase IIb trial investigating efficacy of transdermal segesterone acetate (Nestorone) plus testosterone gel has enrolled over 460 couples with completion estimated for late 2024. A second hormonal method, dimethandrolone undecanoate, is in two clinical trials focusing on safety, pharmacodynamics, suppression of spermatogenesis and hormones; the first of these two is estimated for completion in December 2024. There are also several non-hormonal methods with strong potential in preclinical stages of development. CONCLUSIONS: There exist several hurdles to novel male contraception. Therapeutic development takes decades of time, meticulous work, and financial investment, but with so many strong candidates it is our hope that there will soon be several safe, effective, and reversible contraceptive options available to male patients.

RéSUMé: CONTEXTE: Depuis la sortie de la pilule contraceptive orale combinée en 1960, les femmes ont assumé le fardeau de la contraception et de la planification familiale. Plus de 60 ans plus tard, c'est toujours le cas, car les seules options contraceptives pratiques et efficaces disponibles pour les hommes sont les préservatifs et la vasectomie. Cependant, il existe maintenant une variété d'options contraceptives masculines hormonales et non hormonales prometteuses qui sont à l'étude. Le but de cette revue narrative est de fournir aux cliniciens et aux profanes des descriptions ciblées et à jour de nouvelles stratégies et cibles pour la contraception masculine. Nous incluons une discussion prudemment optimiste sur les avantages et les inconvénients potentiels, en soulignant plusieurs méthodes aux stades précliniques et cliniques du développement. RéSULTATS: En juin 2023, deux méthodes contraceptives masculines hormonales faisaient l'objet d'essais cliniques de phase II pour leur innocuité et leur efficacité. Un essai international de phase IIb à grande échelle, portant sur l'efficacité de l'acétate de ségestérone transdermique (Nestorone) et du gel de testostérone, a recruté plus de 460 couples et devrait être achevé pour la fin de 2024. Une seconde méthode hormonale, l'undécanoate de diméthandrolone, fait l'objet de deux essais cliniques axés sur l'innocuité, la pharmacodynamique, la suppression de la spermatogenèse et des hormones; le premier de ces deux essais devrait être achevé en décembre 2024. Il existe également plusieurs méthodes non hormonales à fort potentiel aux stades précliniques de développement. CONCLUSIONS: Il existe plusieurs obstacles à la nouvelle contraception masculine. Le développement thérapeutique nécessite des décennies de temps, un travail méticuleux et un investissement financier ; mais avec autant de candidats solides, nous espérons qu'il y aura bientôt plusieurs options contraceptives sûres, efficaces et réversibles, disponibles pour les hommes.

Interaction of endocannabinoid system and cyclooxygenase metabolites with fatty acid amide hydrolase and cyclooxygenase enzyme activities on contractile responses in rat vas deferens tissue.

The endocannabinoid system and prostaglandins are important modulators in the genitourinary system. This study aimed to investigate the possible interactions between the endocannabinoid system and the cyclooxygenase (COX) pathway on rat vas deferens. For this purpose, the concentration responses of the endocannabinoid anandamide, prostaglandin F2α analog latanoprost, and prostaglandin E1 analog misoprostol on the electrical field stimulation (EFS)-induced contractile responses were obtained. The concentration responses to anandamide were obtained again in the presence of nonselective COX inhibitor flurbiprofen and prostaglandin analogs, while the concentration responses of latanoprost and misoprostol were obtained in the presence of cannabinoid receptor antagonists and fatty acid amide hydrolase (FAAH) enzyme inhibitor URB597. FAAH, COX-1, and COX-2 enzyme levels in vas deferens tissue samples were also determined. The cumulative addition of anandamide was not different from the vehicle; however, the EFS-induced contractile responses were significantly increased with the incubation of latanoprost or flurbiprofen in the prostatic portion. Flurbiprofen and misoprostol decreased FAAH enzyme levels in both portions of the vas deferens, while latanoprost induced the inhibition in the prostatic portion. The cumulative administration of latanoprost and misoprostol significantly enhanced the contractile responses in the prostatic portion. This effect of latanoprost was significantly antagonized by URB597 and AM251. The enhancing effect of misoprostol was antagonized by anandamide, URB597, AM251, and AM630. Anandamide, AM251, AM630, and URB597 decreased enzyme levels of COX-1 and COX-2 in both portions of the vas deferens. These results demonstrate an intricate crosstalk between endocannabinoids and prostaglandins in modulation of the vas deferens contractility.

Unilateral renal agenesis and ipsilateral absence of the vas deferens in a cryptorchid infant with Klippel-Feil syndrome.

We report an exceedingly rare case of Klippel-Feil syndrome (KFS), compounded by ipsilateral absence of the vas deferens, renal agenesis, and diaphragmatic hernia. Unilateral absence of the vas deferens was found incidentally during orchidopexy. To the best of our knowledge, no case of unilateral absence of the kidney and vas deferens has been reported in children with KFS.

The effects of different vasovasostomy techniques on motility of vas deferens (vas motility following vasovasostomy).

PURPOSE: Vasovasostomy is used to correct vas deferens (VD) transections encountered during surgery or to reverse sterilization vasectomies. Achieving vasal patency is the primary goal and the success is assessed on various factors including VD patency, flow rates, and pregnancy rates. While preserving vas motility is not a major concern in surgical practice, it is worth noting that VD has peristaltic activity which plays crucial role during ejaculation. Any disruption in its motility could potentially lead to negative outcomes in the future. We conducted an experimental study to assess vas motility changes following vasovasostomy. METHODS: The study was approved by Gazi University, Animals Ethic Committee. Twenty-four rats were allocated to four groups. Left-sided VD was harvested in control group (Gr1). The rest of the animals were subjected to transection of VD. Gr2 and 3 underwent microscopic and macroscopic anastomosis, respectively, while Gr4 underwent vasal approximation. After 12 weeks, all left-sided VD were resected, electrical field stimulation (EFS) and exogenous drugs were applied to induce contractions. Statistical analyses were performed and p value < 0.05 was regarded as statistically significant. RESULTS: The first and second phases of EFS-induced contractile responses(CR) increased for Gr3 and decreased for Gr4 at submaximal and maximal frequencies. An increase only at maximal frequency for second phase EFS-induced CR was encountered for Gr2. α-ß-methylene-ATP-induced CR decreased for Gr3 and 4. Noradrenaline-induced CR increased for Gr2, and 3 and decreased for Gr4. CONCLUSION: The results suggest that vasovasostomy performed using a surgical technique that minimizes disruption or damage to VD may have a favorable impact on motility.

Heat Shock Proteins Are Differentially Expressed in the Domestic Cat (Felis catus) Testis, Epididymis, and Vas Deferens.

Heat shock proteins (HSPs) play key roles in controlling the morphological transformation of germ cells during spermatogenesis and posttesticular maturation of sperm. This study aims to reveal the presence and localization patterns of large adenosine triphosphate (ATP)-dependent HSPs family members in adult domestic cat testis and excurrent ducts utilizing Western blot, immunohistochemistry, and immunofluorescence techniques. The results indicated that the relative amounts of heat shock protein D1 (HSPD1)/HSP60, heat shock protein C (HSPC)/HSP90, and heat shock protein H (HSPH)/HSP105/110 were highest in the testis, while heat shock protein A (HSPA)/HSP70 was highest in the corpus epididymis. HSPs exhibited spermatogenic stage-dependent localization patterns in germ cells. Sertoli and Leydig cells were positive for other HSPs except for HSPC/HSP90. The tubules rectus and rete testis epithelia showed only HSPD1/HSP60 and HSPA/HSP70 immunoreactivity, while the ciliated cells of efferent ductules were positive for all HSPs. In the epididymis and vas deferens, HSPs localizations were cell and region specific. HSPD1/HSP60 was localized in the midpiece of the immature spermatozoa tail, while HSPA/HSP70 and HSP90 were found only in the proximal cytoplasmic droplet (CD). HSPH/HSP105 was observed in CD and the principal piece but not the midpiece. Overall, the different expression of HSPs throughout the domestic cat testis and excurrent ducts indicates their critical roles in maintaining reproductive functions under physiological conditions.

Development of a nomogram for the early prediction of PACU VAS in patients undergoing laparoscopic radical resection of colorectal cancer with fentanyl.

Introduction: To make early predictions of PACU VAS before surgery, we created a novel nomogram for the early prediction of PACU VAS in patients having laparoscopic radical excision of colorectal cancer with fentanyl. Methods: From July 2018 to December 2020, a total of 101 patients in Zhongshan Hospital Affiliated to Fudan University who underwent laparoscopic radical resection of colorectal cancer were enrolled in this study. For feature selection, a stepwise regression model was utilized. Multivariable logistic regression analysis was used to establish a prediction model. We incorporated age, gender, weight, height, fentanyl dosage during operation, operation time, and OPRM1 genotype, and this was presented with a nomogram. The nomogram's performance was evaluated in terms of discrimination and clinical utility. Results: The signature, which comprised of seven carefully chosen characteristics, was linked to the PACU VAS for the development dataset. Predictors contained in the individualized prediction nomogram included age, gender, weight, height, fentanyl dosage during operation, operation time, and OPRM1 genotype. With an area under the ROC curve of 0.877 (95% CI, 0.6874-1.0000), the model showed good discrimination. The nomogram still had good discrimination. Decision curve analysis demonstrated that the nomogram was clinically useful. Conclusions: The nomogram presented in this study incorporates age, gender, weight, height, fentanyl dosage during operation, operation time, and OPRM1 genotype and can be conveniently used to facilitate the individualized prediction of PACU VAS in patients undergoing laparoscopic radical resection of colorectal cancer with fentanyl.

Effects of RS17053 on α1 -adrenoceptors in rat vas deferens and aorta.

BACKGROUND: RS17053 is classed as an α1A -adrenoceptor selective antagonist. OBJECTIVES: We have examined its profile of action at all subtypes of α1 -adrenoceptor. METHODS: Noradrenaline (NA) evoked contractions of rat vas deferens involve α1D -adrenoceptors in phasic contractions and α1A -adrenoceptors in tonic contractions. Contractions of rat aorta to NA involve α1D - and α1B -adrenoceptors. RESULTS: RS17053 (10-5  M) shifted NA potency and virtually abolished tonic contractions to NA, with little or limited effect on phasic contractions. The α1D -adrenoceptor antagonist BMY7378 (3 × 10-7 M) significantly inhibited the remaining phasic component of the contractions, and the α1A -adrenoceptor antagonist RS100329 (10-7  M) inhibited further the residual tonic contraction. Hence, RS17053 shows high selectivity for α1A -adrenoceptors over α1D -adrenoceptors in rat vas deferens. However, RS17053 (10-5  M) produced a large shift in the potency of NA in rat aorta, with a pKB of 6.82. Large shifts of NA potency in rat aorta involve α1B -adrenoceptor blockade. CONCLUSION: Results in rat vas deferens demonstrate low potency of RS17053 at α1D -adrenoceptors, but results from rat aorta can only be explained as demonstrating α1B -adrenoceptor antagonism by RS17053. RS17053 may be a useful pharmacological tool when reclassified as a mainly α1A - and to a lesser extent α1B -adrenoceptor antagonist with little effect at α1D -adrenoceptors.

Compound heterozygous variants in CFTR with potentially reducing ATP-binding ability identified in Chinese infertile brothers with isolated congenital bilateral absence of vas deferens.

BACKGROUND: Isolated congenital bilateral absence of vas deferens (iCBAVD) in men results in obstructive azoospermia and is mainly caused by pathogenic variants in cystic fibrosis transmembrane conductance regulator (CFTR) or adhesion G protein-coupled receptor G2 (ADGRG2). METHODS: The next-generation sequencing (NGS) was used to screen the mutations in the proband, and Sanger sequencings were performed to validate the compound heterozygous variant of CFTR in his family members. Protein structure simulation was performed to discover the potential pathological mechanism. RESULTS: This study reported novel compound heterozygous CFTR mutations (NM:000492.4, Intron: 5T; c.3965_3969dupTTGGG: p.R1325Gfs*5) in two brothers with obstructive azoospermia. The compound heterozygous CFTR mutations were first screened out by NGS in an infertile male patient who exhibited iCBAVD from a nonconsanguineous Chinese family. Histological analysis of the testicular biopsy from this patient revealed normal spermatogenesis and mature spermatozoa were observed in the seminiferous tubules. Surprisingly, the same compound heterozygous CFTR mutations were also observed in his brothers who also exhibited iCBAVD, with their parents being a heterozygous carrier for the mutations, as verified by Sanger sequencing. Protein structure simulation revealed that these mutations potentially led to impaired ATP-binding ability of CFTR. CONCLUSION: We identified novel compound heterozygous CFTR mutations in two brothers and summarized the literature regarding CFTR mutation and male infertility. Our study may contribute to the genetic diagnosis of iCBAVD and future genetic counseling.