Azelaic acid can efficiently compete for the auxin binding site TIR1, altering auxin polar transport, gravitropic response, and root growth and architecture in Arabidopsisthaliana roots.

The present study investigates the phytotoxic potential of azelaic acid (AZA) on Arabidopsis thaliana roots. Effects on root morphology, anatomy, auxin content and transport, gravitropic response and molecular docking were analysed. AZA inhibited root growth, stimulated lateral and adventitious roots, and altered the root apical meristem by reducing meristem cell number, length and width. The treatment also slowed down the roots' gravitropic response, likely due to a reduction in statoliths, starch-rich organelles involved in gravity perception. In addition, auxin content, transport and distribution, together with PIN proteins' expression and localisation were altered after AZA treatment, inducing a reduction in auxin transport and its distribution into the meristematic zone. Computational simulations showed that AZA has a high affinity for the auxin receptor TIR1, competing with auxin for the binding site. The AZA binding with TIR1 could interfere with the normal functioning of the TIR1/AFB complex, disrupting the ubiquitin E3 ligase complex and leading to alterations in the response of the plant, which could perceive AZA as an exogenous auxin. Our results suggest that AZA mode of action could involve the modulation of auxin-related processes in Arabidopsis roots. Understanding such mechanisms could lead to find environmentally friendly alternatives to synthetic herbicides.

The challenging management of malignant ureteral obstruction: Analysis of a series of 188 cases.

Background: Malignant ureteral obstruction (MUO) is a common condition that complicates the course of advanced malignancies. The aims of this study are to analyze the causes, management, and survival of patients with obstructive nephropathy due to malignant ureteric obstruction and to determine prognostic factors. Furthermore, we studied the complications and outcomes in patients who underwent urinary diversion. Materials and methods: A retrospective study was conducted on patients with computed tomography-confirmed MUO between January 2016 and November 2020. Demographic, clinical, radiological, laboratory, and management data were collected. Survival curves were estimated using the Kaplan-Meier method, and univariate and multivariate Cox proportional hazards models were used to test the association between parameters and survival. Results: A total of 188 patients were included. The mean age was 69.01 years (SD, 14.95 years), and the majority (54.8%) were male. The most common mechanism leading to MUO was compression by a pelvic mass (36.9%), and the 3 most frequent tumors causing MUO were prostate (17.6%), bladder (16.5%), and rectal cancer (11.7%).Forty-seven patients (25%) underwent urinary diversion: 23 (48.9%) underwent double-J stenting and 21 (44.7%) underwent percutaneous nephrostomy. The most common reason for urinary diversion was acute kidney injury (53.3%). Recovery of renal function was observed in 55.8% of the patients after urinary diversion. The most frequently identified complications after urinary diversion were urinary tract infection (24.4%), hematuria (17.0%), and urinary sepsis (14.9%). The median survival after hydronephrosis diagnosis was 6.43 months (interquartile range, 1.91-14.81 months). In patients who underwent urinary decompression, the median survival after urinary diversion was 8.67 months (interquartile range, 2.99-17.28 months). In the multivariate analysis, a lower grade of hydronephrosis and cancer cachexia negatively impacted survival. Conclusions: Cancer patients with MUO have a poor prognosis; therefore, the risk-benefit ratio of urinary diversion should be carefully considered. Cachexia and hydronephrosis grade can be useful in selecting suitable candidates for urinary diversion.

Short-term exposition to acute cadmium toxicity induces the loss of root gravitropic stimuli perception through PIN2-mediated auxin redistribution in Arabidopsis thaliana (L.) Heynh.

Cadmium (Cd), one of the most widespread and water-soluble polluting heavy metals, has been widely studied on plants, even if the mechanisms underlying its phytotoxicity remain elusive. Indeed, most experiments are performed using extensive exposure time to the toxicants, not observing the primary targets affected. The present work studied Cd effects on Arabidopsis thaliana (L.) Heynh's root apical meristem (RAM) exposed for short periods (24 h and 48 h) to acute phytotoxic concentrations (100 and 150 µM). The effects were studied through integrated morpho-histological, molecular, pharmacological and metabolomic analyses, highlighting that Cd inhibited primary root elongation by affecting the meristem zone via altering cell expansion. Moreover, Cd altered Auxin accumulation in RAM and affected PINs polar transporters, particularly PIN2. In addition, we observed that high Cd concentration induced accumulation of reactive oxygen species (ROS) in roots, which resulted in an altered organization of cortical microtubules and the starch and sucrose metabolism, altering the statolith formation and, consequently, the gravitropic root response. Our results demonstrated that short Cd exposition (24 h) affected cell expansion preferentially, altering auxin distribution and inducing ROS accumulation, which resulted in an alteration of gravitropic response and microtubules orientation pattern.

Application of Indole-Alkaloid Harmaline Induces Physical Damage to Photosystem II Antenna Complexes in Adult Plants of Arabidopsis thaliana (L.) Heynh.

Finding herbicides with new and multiple modes of action is a solution to stop the increase in resistant weed species. Harmaline, a natural alkaloid with proven phytotoxic potential, was tested on Arabidopsis adult plants by watering and spraying; watering resulted as the more effective treatment. Harmaline altered several photosynthetic parameters, reducing the efficiency of the light- (ΦII) and dark-adapted (Fv/Fm) PSII, suggesting physical damages in photosystem II, although dissipation of the energy in excess under the form of heat was not compromised as demonstrated by the significant increase in ΦNPQ. Metabolomic alterations, such as osmoprotectant accumulation and reduction in sugars' content, also indicate a reduction of photosynthetic efficiency and suggest early senescence and water status alteration induced by harmaline. Data suggest that harmaline might be considered a new phytotoxic molecule interesting for further studies.

Androgen Receptor Signaling Inhibition in Advanced Castration Resistance Prostate Cancer: What Is Expected for the Near Future?

The androgen signaling pathway is the cornerstone in the treatment of high risk or advanced prostate cancer patients. However, in recent years, different mechanisms of resistance have been defined in this field, limiting the efficacy of the currently approved antiandrogen drugs. Different therapeutic approaches are under research to assess the role of combination therapies against escape signaling pathways or the development of novel antiandrogen drugs to try to solve the primary or acquired resistance against androgen dependent or independent pathways. The present review aims to summarize the current state of androgen inhibition in the therapeutic algorithm of patients with advanced prostate cancer and the mechanisms of resistance to those available drugs. In addition, this review conducted a comprehensive overview of the main present and future research approaches in the field of androgen receptor inhibition to overcome these resistances and the potential new drugs under research coming into this setting.

Ultrastructural and hormonal changes related to harmaline-induced treatment in Arabidopsis thaliana (L.) Heynh. root meristem.

Harmaline is an indole alkaloid with demonstrated phytotoxicity and recognized pharmacological applications. However, no information is available concerning its mode of action on plant metabolism. Therefore, the present work evaluated bioherbicide mode of action of harmaline on plant metabolism of Arabidopsis thaliana (L.) Heynh. Harmaline induced a strong inhibitory activity on root growth of treated seedlings, reaching IC50 and IC80 values of 14 and 29 µM, respectively. Treated roots were shorter and thicker than control and were characterized by a shorter root meristem size and an increase of root hairs production. Harmaline induced ultrastructural changes such as increment of cell wall thickness, higher density and condensation of mitochondria and vacuolization, appearance of cell wall deposits, increment of Golgi secretory activity and higher percentage of aberrant nuclei. The ethylene inhibitor AgNO3 reversed high root hair appearance and increment of root thickness, and pTCSn::GFP transgenic line showed fluorescence cytokinin signal in stele zone after harmaline treatment that was absent in control, whereas the auxin signal in the transgenic line DR5 was significantly reduced by the treatment. All these results suggest that the mode of action of harmaline could be involving auxin, ethylene and cytokinin synergic/antagonistic action.

[Renal allograft transplant vascular complications. Diagnostic and treatment.] / Complicaciones vasculares del trasplante renal. Diagnóstico y tratamiento.

Vascular complications remain common after renal transplantation, occurring in 3% to 15% of patients. These complications can compromise graft function,with graft loss rates ranging from 12.6 to 66.7%.Vascular abnormalities of the graft, specifically the presence of multiple vessels, represent the most frequently studied risk factor for the development of vascular complications. Other risk factors identified for the development of vascular complications are linked to the characteristics of the recipient, or thromboembolic diseasesharing atherosclerosis and/or hypercoagulant state aspathogenic features.Although the most frequent vascular complication is renal artery stenosis, we will also address the complications according to their early or late on set in order to highlightthe potentially more severe complications that may affectgraft survival during the follow-up period.Early vascular complications include mainly arterial and venous thrombosis and lacerations or disruptions of artery and/or vein, as well as arterio-venous fistulas or intrarenal pseudoaneurysms. In contrast, late-onset complications include stenosis or kinking of the renal artery-and less commonly of the renal vein-, as well as extrinsic compression as a consequence of the presence of perigraft fluid collections. Finally, extrarenal pseudoaneurysm is a potentially severe complication in the late post-transplant period.Finally, this article explores special transplant situations such as complications derived from the paediatric donor in adult recipients, transplantation in the paediatric recipient and emerging techniques like robotic renal transplantation.

Las complicaciones vasculares siguen siendo frecuentes después del trasplante renal, ocurriendo entre el 3% y el 15% de los pacientes. Estas complicaciones pueden comprometer la función del injerto,con unas tasas de pérdida del injerto que varían entreel 12,6 ­ 66,7%.Las anomalías vasculares del injerto, y concretamente la presencia de múltiples vasos, representan el factor de riesgo más frecuente y estudiado para el desarrollo de complicaciones vasculares. Otros factores de riesgo de complicaciones vasculares se han relacionado con las características del receptor, o la enfermedad tromboembólica, compartiendo como características patogénicas la aterosclerosis y/o el estado hipercoagulante. Aunque la complicación vascular más frecuente está constituida por la estenosis de la arteria renal, expondremos las complicaciones en función de su presentación clínica temprana o tardía en un intento de destacar para el lector las complicaciones potencialmente más severas y que en cada momento del tiempo pueden condicionar la supervivencia del injerto.Las complicaciones de presentación preferentemente perioperatoria incluyen fundamentalmente la trombosis arterial y venosa y las laceraciones o disrupciones de arteria y/o vena, así como las fístulas arterio-venosas opseudoaneurismas intrarrenales. Por el contrario, otras complicaciones tienen comúnmente una presentación clínica más tardía. En este grupo incluimos la estenosiso acodamiento de la arteria renal y excepcionalmente de la vena renal, así como la compresión extrínseca de los vasos del injerto como consecuencia de la presencia de colecciones peri-injerto. Finalmente, una complicación severa que puede manifestarse de forma tardía enla evolución del receptor, es el pseudoaneurisma extrarrenal. Finalmente, haremos brevemente referencia a situaciones especiales del trasplante como las complicaciones derivadas del donante pediátrico en receptores adultos,del trasplante en el receptor pediátrico y de técnicas emergentes como el trasplante renal robótico.

The effect of medical and urologic disorders on the survival of patients with metastatic castration resistant prostate cancer treated with abiraterone or enzalutamide.

INTRODUCTION: Androgenic deprivation therapies have been linked to the development of metabolic syndrome (MS) and cardiovascular diseases, which may lead to a poorer survival in patients with metastatic Castration-Resistant Prostate Cancer (mCRPC). We aimed to analyze whether some cardiovascular or neurological disorders, together with other medical and urological complications, may have an effect on survival outcomes, at baseline and during treatment from patients treated with androgen pathway inhibitors (API). MATERIAL AND METHODS: A retrospective study of a consecutive series of patients diagnosed with mCRPC between 2010 and 2018 treated with API in the first line setting in a single center. RESULTS: Seventy-three patients met the inclusion criteria. Baseline prognostic factors associated with worse survival were diabetes mellitus (DM) with insulin needs compared to patients without DM [hazard ratio (HR) = 0.19, p = 0.025], hypertension (HTN) (HR = 0.46, p = 0.035), and a history of stroke (HR = 0.16, p < 0.001). However, previous history of hypercholesterolemia, arrythmias, and cognitive disorders did not result in a significant worsening on survival. During treatment, patients who developed de novo HTN had the best progression free survival (PFS) (HR = 0.38, p = 0.048) and overall survival (OS) (HR 0.08, p = 0.012) compared with patients with previous HTN. Other factors related to worse outcomes included the presence of heart failure (HR = 0.31, p = 0.001), the requirement for major opioids for pain relief (HR = 0.33, p = 0.023), and the presence of bilateral ureterohydronephrosis (HR = 0.12, p = 0.008). CONCLUSIONS: Some comorbidities may be strongly involved in patient outcomes when receiving API for mCRPC. In this sense, collaborative networking between specialists and caregivers treating prostate cancer (PC) patients should be recommended, focusing on MS features, cardiovascular and neurological disorders in order to anticipate medical and surgical complications.

The Failing Kidney Transplant Allograft. Transplant Nephrectomy: Current State-of-the-Art.

PURPOSE OF REVIEW: This review provides a critical literature overview of the risks and benefits of transplantectomy in patients with a failed allograft. Additionally, it offers a summary of related problems, primarily alloantibody sensitization in the event of nephrectomy and immunosuppression weaning. RECENT FINDINGS: Transplant nephrectomy has high morbidity and mortality rates. The morbidity of transplant nephrectomy (4.3 to 82%) is mostly due to hemorrhage or infection. Mortality rates range from 1.2 to 39%, and most are due to sepsis. Transvascular graft embolization has been described as a less invasive alternative technique for the management of symptomatic graft rejection, with minimal complications compared with transplantectomy. The number of patients with a failed allograft returning to dialysis is increasing. The role of allograft nephrectomy in the management of asymptomatic transplant failure is still controversial and up today continues to depend on the usual clinical practice of each institution. The less invasive transvascular embolization could have applicability in asymptomatic patients with the obvious lower morbidity and mortality rate.

[Current status of androgen deprivation therapy in hormone-sensitive prostate cancer.] / Estado actual de la castración en cáncer de próstata metastásico hormonosensible.

OBJECTIVE: To analyze the current available evidence of androgen deprivation therapy in hormone-sensitive metastatic prostate cancer, focused on the relevance of suppressing circulating testosterone levels and its prognostic significance. To assess the optimal value of castration levels and PSA reduction under hormone treatment. METHODS: We performed a bibliographic review through automatized search in the Pubmed bibliographic database and Clinical Key. The search strategy included the following terms: "prostate cancer" AND "hormones", "metastatic prostate cancer", "testosterone" AND "prostate cancer", "hormone naive/sensitive" AND "prostate cancer". RESULTS: Lower testosterone levels are associated with better survival and have prognostic significance. Values below 32-20 ng/dl, in accordance to different reported studies, have been established as optimal castration levels with clinical significance, with impact on cancer specific survival and time to castration resistance. Similarly, low PSA levels after starting hormone therapy have been suggested as a strong predictor of survival and treatment response. CONCLUSIONS: Close monitoring of PSA and testosterone levels is necessary in patients with metastatic prostate cancer during hormone deprivation treatment. Combination of both values allows to predict treatment response and early identification of tumor progression, and to put forward subsequent therapeutic strategies improving survival in this group of patients.

The Usefulness of Contrast-Enhanced Ultrasound in the Assessment of Early Kidney Transplant Function and Complications.

OBJECTIVES: The routine diagnostic method for assessment of renal graft dysfunction is Doppler ultrasound. However, contrast-enhanced ultrasound (CEUS) may provide more information about parenchymal flow and vascular status of kidney allografts. The aim of the study was to assess the effectiveness of CEUS in the immediate post-transplant period, focusing on acute vascular complications. A brief review of available literature and a report of our initial experience is made. MATERIAL AND METHODS: 15 kidney transplant (KT) cases with clinical suspicion of acute surgical complication were assessed with CEUS and conventional Doppler ultrasound (US). In addition, bibliographic review was conducted through PubMed, Embase, and ClinicalKey databases. RESULTS: 10% of KT underwent CEUS, useful for detecting vascular complication or cortical necrosis in 4 (26%) and exclude them in 74%. Grafts with acute vascular complications have a delayed contrast-enhancement with peak intensity lower than normal kidneys. Perfusion defects can be clearly observed and the imaging of cortical necrosis is pathognomonic. CONCLUSIONS: CEUS is a useful tool in the characterization of renal graft dysfunction with special interest on acute vascular complications after renal transplant. It is a feasible technique for quantitative analysis of kidney perfusion, which provides information on renal tissue microcirculation and regional parenchymal flow. Exploration could be done by a urologist at the patient's bedside while avoiding iodinated contrast.

Genital self-mutilation. Case report and bibliographic review.

OBJECTIVE: To report a very uncommon case of penile open wound made by self-mutilation in a 51-year-old man, and to perform a bibliographic review. METHODS: 51-year-old man presenting at the Emergency Department under Police guard after self-cutting his penis while he was urinating, presenting an almost complete circular section that required immediate surgical repair. RESULTS: Early surgical management showed the section of almost the whole penile circumference, from ventral to dorsal, including urethra and both cavernous bodies, respecting only the dorsal vascular penile complex. We performed a primary anastomosis of the damaged structures and careful haemostasis of the penis. CONCLUSIONS: Open traumas to the penis usually require an urgent surgical examination, being mandatory to try a primary reconstruction if the global clinical situation allows it. Cosmetic and functional postoperative results advise this attitude.

Bibliographic review about the usefulness of ultrasound contrast media in the study of renal masses.

OBJECTIVES: The microbubbles enhanced ultrasound contrast is a novel technique that informs us in real time of renal perfusion and microcirculation. METHOD: We reviewed the literature about its use in the study of renal masses in order to show their actual clinical performance in this condition. RESULT: This technique is useful in the differential diagnosis of pseudotumors, characterization and monitoring of small renal masses, the study of complex renal cysts and controlling the progression of renal masses that underwent ablative treatments. Like any diagnostic technique has some limitations on usage;its rapid contrast wash, being operator-dependent, require some experience and need special software to be correctly interpreted. CONCLUSIONS: The microbubbles enhanced ultrasound contrast is a useful and economic technique for the study and differential diagnosis of the renal masses.