Telemedicine and social media: A contemporary analysis of the most shared content by internet users.

OBJECTIVE: To evaluate the telemedicine information published on the most popular social media platforms, during the second year of the COVID-19 pandemic. METHODS: We queried the BuzzSumo tool to identify related telemedicine article links that were shared most on social media, from February 2021 to February 2022. The PEMAT-P was used for the quality assessment of the most shared links. RESULTS: 125 links were eligible for the analysis. Facebook was the most used social media platform for sharing articles (median engagement: 1000). Most of the articles were published by magazines (n = 82, 65.6%) and the main topic addressed was general information (n = 49, 39.2%). In the subgroup analyses of the 34 most shared articles, Facebook was the most used social media platform (median engagement:1950), most of the articles were published by magazines (n = 24, 70.6%), whereas the main topic addressed was the prescription of the abortion pill (n = 9, 26.5%). According to the PEMAT-P tool, the median understandability and actionability score was 63.8 and 20%, respectively. CONCLUSIONS: The interest in telemedicine has increased all over the world, as evidenced by the high engagement in social media articles, recorded during the last year. However, the access to digital health services is still limited, the information provided is often not verified by an official entity and unable to fill the digital divide exacerbated by COVID 19 pandemic crisis. Hence, health policy should be developed or modified to ensure a more egalitarian Internet access for all citizens. Official medical institutions should standardize telemedicine regulation and online content to reduce the widespread of misleading information.

Carbapenem-Resistant Enterobacteriaceae in Urinary Tract Infections: From Biological Insights to Emerging Therapeutic Alternatives.

Urinary tract infections (UTIs) are the second most frequent type of infection observed in clinical practice. Gram-negative Enterobacteriaceae are common pathogens in UTIs. Excessive antibiotic use in humans and animals, poor infection control, and increased global travel have accelerated the spread of multidrug-resistant strains (MDR). Carbapenem antibiotics are commonly considered the last line of defense against MDR Gram-negative bacteria; however, their efficacy is now threatened by the increasing prevalence of carbapenem-resistant Enterobacteriaceae (CRE). This comprehensive review aims to explore the biological mechanisms underlying carbapenem resistance and to present a focus on therapeutic alternatives currently available for complicated UTIs (cUTIs). A comprehensive bibliographic search was conducted on the PubMed/MEDLINE, Scopus, and Web of Science databases in December 2023. The best evidence on the topic was selected, described, and discussed. Analyzed with particular interest were the clinical trials pivotal to the introduction of new pharmacological treatments in the management of complicated cUTIs. Additional suitable articles were collected by manually cross-referencing the bibliography of previously selected papers. This overview provides a current and comprehensive examination of the treatment options available for CRE infections, offering a valuable resource for understanding this constantly evolving public health challenge.

The Role of miRNA in Testicular Cancer: Current Insights and Future Perspectives.

Background and Objectives: Despite advancements in the diagnosis and treatment of testicular germ cell tumours (TGTCs), challenges persist in identifying reliable biomarkers for early detection and precise disease management. This narrative review addresses the role of microRNAs (miRNAs) as potential diagnostic tools and therapeutic targets in the treatment of TGCTs. Materials and Methods: Three databases (PubMed®, Web of Science™, and Scopus®) were queried for studies investigating the utility of miRNA as diagnostic tools, assessing their prognostic significance, and evaluating their potential to guide TGCT treatment. Different combinations of the following keywords were used, according to a free-text protocol: "miRNA", "non-coding RNA", "small RNA", "Testicular Cancer", "seminomatous testicular germ cell", "non-seminomatous testicular germ cell". Results: The potential of miRNAs as possible biomarkers for a non-invasive diagnosis of TGCT is appealing. Their integration into the diagnostic pathway for TGCT patients holds the potential to enhance the discriminative power of conventional serum tumour markers (STMs) and could expedite early diagnosis, given that miRNA overexpression was observed in 50% of GCNIS cases. Among miRNAs, miR-371a-3p stands out with the most promising evidence, suggesting its relevance in the primary diagnosis of TGCT, particularly when conventional STMs offer limited value. Indeed, it demonstrated high specificity (90-99%) and sensitivity (84-89%), with good positive predictive value (97.2%) and negative predictive value (82.7%). Furthermore, a direct relationship between miRNA concentration, disease burden, and treatment response exists, regardless of disease stages. The initial evidence of miRNA decrease in response to surgical treatment and systemic chemotherapy has been further supported by more recent results suggesting the potential utility of this tool not only in evaluating treatment response but also in monitoring residual disease and predicting disease relapse. Conclusions: MiRNAs could represent a reliable tool for accurate diagnosis and disease monitoring in the treatment of TGCT, providing more precise tools for early detection and treatment stratification. Nevertheless, well-designed clinical trials and comprehensive long-term data are needed to ensure their translation into effective clinical tools.

"Nocturia and obstructive sleep apnea syndrome: A systematic review".

Lower urinary tract symptoms represent a significant public health problem worldwide, impairing patients' quality of life, especially in elderly people. Among LUTS, nocturia is assessed as the most experienced entity related to several disorders such as sleep disorders and/or obstructive sleep apnea syndrome (OSAS). Among OSAS patients, nocturia stands as a bothersome symptom that increases alongside with the OSAS severity. However, despite the nocturia and OSAS shared a long-acknowledged link, the causes, and the pathophysiology for development of nocturia in OSAS have remained largely unexamined. Generally, the patients with OSAS experienced nocturia due to easy waking or increased bladder filling. However, nor the effect of treatment on management of nocturia in OSAS patients are well-established.

Telemedicine and YouTube™: Video quality analysis before and after COVID-19 pandemic.

OBJECTIVE: To assess the quality content of YouTubeTM videos on telemedicine during COVID-19 pandemic. MATERIALS AND METHODS: First, the frequency of worldwide YouTube™ and Google™ searches for telemedicine was analyzed. Second, we queried YouTube™ with telemedicine-related terms. Third, the Patient Education Materials Assessment Tool for Audiovisual Materials (PEMAT A/V), the Global Quality Score (GQS), and the Misinformation tool were used for the quality assessment. RESULTS: According to selection criteria, 129 videos were collected for the analysis. From January 2018 to January 2022, the peak relative interest on YouTube™ and Google™ occurred in March 2020. Of all, 27.1 and 72.9% were uploaded before (Jan 2018-Feb 2020) and after (Mar 2020-Mar 2022) the COVID-19 outbreak, respectively. According to the PEMAT A/V, the overall median understandability and actionability was 50.0% (33.3 [IQR 0-66.7] vs 50.0 [27.1-75], p = 0.2) and 66.7% (63.6 [IQR 50.0-75.7] vs 67.9 [50.0-79.2],p = 0.6), respectively. According to GQS, 3.9%, 17.8%, 24.0%, 26.4% and 27.9% were classified as excellent, good, medium, generally poor, and poor-quality videos, respectively. The highest rate of poor-quality videos was recorded in videos uploaded before COVID-19 pandemic (37.1 vs 24.5%). According to overall misinformation score, a higher score was recorded for the videos uploaded after COVID-19 pandemic (1.8 [IQR 1.4-2.3] vs 2.2 [1.8-2.8], p = 0.01). CONCLUSIONS: The interest in telemedicine showed a significant peak when the COVID-19 pandemic was declared. However, the contents provided on YouTubeTM were not informative enough. In the future, official medical institutions should standardize telemedicine regulation and online content to reduce the widespread of misleading information.

Cytoreductive Nephrectomy and Metastatic Renal Cell Carcinoma: State of the Art and Future Perspectives.

In the past decades, several treatments have been proposed for the management of metastatic renal cell carcinoma (mRCC). Among these, cytoreductive nephrectomy (CN) represents a controversial and open issue in the era of targeted therapy and novel immunotherapy with immune checkpoint inhibitors. Two important studies, CARMENA and SURTIME, analyzed therapy with sunitinib with or without CN, and immediate CN followed by sunitinib versus a deferred CN after three cycles of sunitinib, respectively. CARMENA showed the non-inferiority of sunitinib alone versus sunitinib plus CN, whereas SURTIME showed no difference in progression-free survival (PFS), but a better median OS among patients with deferred CN. Therefore, more prospective clinical trials and appropriate patient identification are necessary to support CN in this new scenario. This review provides a snapshot of the current evidence for CN in mRCC, discusses the management strategies, and offers perspectives on the direction of future research.

Incidence and Predicting Factors of Histopathological Features at Robot-Assisted Radical Prostatectomy in the mpMRI Era: Results of a Single Tertiary Referral Center.

Background and Objectives: To describe the predictors of cribriform variant status and perineural invasion (PNI) in robot-assisted radical prostatectomy (RARP) histology. To define the rates of upgrading between biopsy specimens and final histology and their possible predictive factors in prostate cancer (PCa) patients undergoing RARP. Material and Methods: Within our institutional database, 265 PCa patients who underwent prostate biopsies and consecutive RARP at our center were enrolled (2018-2022). In the overall population, two independent multivariable logistic regression models (LRMs) predicting the presence of PNI or cribriform variant status at RARP were performed. In low- and intermediate-risk PCa patients according to D'Amico risk classification, three independent multivariable LRMs were fitted to predict upgrading. Results: Of all, 30.9% were low-risk, 18.9% were intermediate-risk and 50.2% were high-risk PCa patients. In the overall population, the rates of the cribriform variant and PNI at RARP were 55.8% and 71.1%, respectively. After multivariable LRMs predicting PNI, total tumor length in biopsy cores (>24 mm [OR: 2.37, p-value = 0.03], relative to <24 mm) was an independent predictor. After multivariable LRMs predicting cribriform variant status, PIRADS (3 [OR:15.37], 4 [OR: 13.57] or 5 [OR: 16.51] relative to PIRADS 2, all p = 0.01) and total tumor length in biopsy cores (>24 mm [OR: 2.47, p = 0.01], relative to <24 mm) were independent predicting factors. In low- and intermediate-risk PCa patients, the rate of upgrading was 74.4% and 78.0%, respectively. After multivariable LRMs predicting upgrading, PIRADS (PIRADS 3 [OR: 7.01], 4 [OR: 16.98] or 5 [OR: 20.96] relative to PIRADS 2, all p = 0.01) was an independent predicting factor. Conclusions: RARP represents a tailored and risk-adapted treatment strategy for PCa patients. The indication of RP progressively migrates to high-risk PCa after a pre-operative assessment. Specifically, the PIRADS score at mpMRI should guide the decision-making process of urologists for PCa patients.

Mobile health applications in kidney stone disease management: A reliable support for patients?

INTRODUCTION: Mobile health applications (MHAs) represent an interesting issue to assist and improve the quality of life of patients affected by Kidney Stone Disease (KSD). Despite this, their scientific quality and adherence to guidelines are not yet addressed. MATERIAL AND METHODS: On 2 November 2022, we conducted an observational cross-sectional descriptive study of all MHAs on KSD. A search in the Apple App Store and Google Play Store was performed. We reviewed all mobile apps from Apple App Store and Google Play Store for KSD and evaluated their usage in screening, prevention, management, and adherence to EAU guidelines. RESULTS: In total 13 MHA were included in the final analysis. All MHAs, 4 (30.8%) from the Apple App Store and 9 (69.2%) from the Google Play Store are geared towards the patient. Engagement ranged from 1.73 to 4.06; Functionality ranged from 3.17 to 4.75; Aesthetics ranged from 1.9 to 4.12; Information ranged from 2.25 to 4.27, and Subjective quality ranged from 1.58 to 3.23. MHAs reported low and medium adherence to EAU guidelines. CONCLUSIONS: MHAs provide a very useful assistance in several medical fields, including KSD. Despite MHAs development is constantly increasing, the scientific validation, content, and quality are not yet solved. Future research is necessary to improve the quality of the apps and promote new user designed, and high-quality apps.

Male infertility, what Mobile Health Applications "know": quality analysis and adherence to European Association of Urology Guidelines.

INTRODUCTION: Male infertility (MI) is one of the most important worrying topics for the fertile age population. Nowadays, several mobile health applications (MHAs) have been developed to help and assist patients suffering from male infertility (MI), but their quality and adherence to the guidelines is not solved issue yet. MATERIALS AND METHODS: On 2nd July 2022, an observational cross-sectional descriptive study of all MHAs on male infertility was conducted: a search on both the iTunes App Store and Google Play Store was performed. Our group reviewed all MHAs, evaluating the quality, using Mobile Application Rating Scale (MARS), and the adherence to European Association of Urology guidelines, with a special tool created for this manuscript. RESULTS: In the final analysis we included 10 MHAs: 20% (n = 2) from the iTunes App Store and 80% (n = 8) from the Google Play Store. Across the sample, 80% (n = 8) of the apps provided general information on MI, 60% (n = 6) focused on diagnosis and 50% (n = 5) focused on treatment options, respectively. According to MARS tool, the mean score was 2.18 (0.78), 3.78 (0.36), 3.0 (0.53), 3.19 (0.45), 2.18 (0.54) for Engagement, Functionality, Aesthetic, Information and Subjective quality, respectively. According to EAU Adherence Score, the highest score was reported by "Infertilità" with 12/15 points while the lowest score was reported by "Fertility Diet Guide", 0/15 points. CONCLUSIONS: Nowadays, MHAs present in the market are not a reliable source of information on MI. An ideal MHAs should be based on scientific evidence, user friendly, respecting privacy and security laws, making patients feel capable and confident to change personal behavior or attitudes.

Perceptions and attitudes toward the use of telemedicine for the postoperative outpatient urological care during the COVID-19 pandemic in an Academic Hospital in Southern Italy.

INTRODUCTION: Telemedicine is a most used tools in various medical and surgical scenarios. The aim of the present study was to explore attitudes and perceptions by urologic patients toward the use of telemedicine in the context of patient-physicians communication during the post-operative follow-up in a large academic tertiary urology referral department in Italy. MATERIALS AND METHODS: An anonymous questionnaire consisting of 15 multiple choice questions was designed including three sections: respondents' demographics, attitudes, and perceptions towards the use of telemedicine. Invitations to participate to this anonymous questionnaire was given to outpatients attended at Urology Department, University of Naples Federico II. RESULTS: In total 697 responses were received (participation rate 73%). The frequency of telemedicine use was described as frequently, occasional, rarely, and never by 41.6%, 30.4%, 15.1%, and 12.6% of respondents, respectively. WhatsApp messenger used by 59.5% of respondents and telephone call (34.3%) were the most common type of tools. Satisfaction in using telemedicine was reported as very satisfied, satisfied, neutral, dissatisfied, and very dissatisfied by 39.6%,41.4%,10%,7% and 2% of respondents respectively. Overall, 43.7%% of participants individuated limited interaction and risk of misdiagnosis as the major limit of telemedicine. CONCLUSIONS: Telemedicine represents the future of medical practice due to several benefits as well as convenience, increased access to care and decreased healthcare costs.

Premature ejaculation in the era of mobile health application: A current analysis and evaluation of adherence to EAU guidelines.

INTRODUCTION: Several mobile health applications (MHAs) have been developed to assist and improve the quality of life of patients affected by premature ejaculation, but the scientific quality and adherence to guidelines are not yet addressed. MATERIALS AND METHODS: On 25 May 2022, we conducted a search in the Apple App Store and Google Play Store. We reviewed all mobile apps from Apple App Store and Google Play Store for premature ejaculation and evaluated their usage in screening, prevention, management, and adherence to EAU guidelines. RESULTS: In total 9 MHA were reviewed. All MHAs are geared towards the patient and provide information about diagnoses and treatment of PE. The mean score were 2.87, 3.69, 2.77, 2.55, 2.86 for Engagement, Functionality, Aesthetics, Information, and Subjective quality respectively. MHAs reported low and medium adherence to EAU guidelines. CONCLUSIONS: MHAs provide different services in many medical fields, including male sexual dysfunction. Their development is constantly increasing, but the problems of scientific validation, content, and quality are not yet solved. Much future research is necessary to improve the quality of the apps and promote new user designed, and high-quality apps.

Natural treatments for erectile dysfunction: A focus on mobile health applications.

To the Editor, Erectile dysfunction (ED) is defined as the persistent inability to achieve or maintain penile erection sufficient for satisfactory sexual performance. ED represents one of the most important male sexual dysfunctions with a prevalence of 52% and affecting more than 150 million men worldwide (estimated to be 322 million worldwide for 2025) [...].

Erectile dysfunction and mobile phone applications: Quality, content and adherence to European Association guidelines on male sexual dysfunction.

INTRODUCTION: Nowadays numerous mobile health applications (MHA) have been developed to assist and simplify the life of patients affected by erectile dysfunction (ED), however the scientific quality and the adherence to guidelines are not yet addressed and solved. MATERIALS AND METHODS: On 17 January 2022, we conducted a search in the Apple App Store and Google Play Store.We reviewed all mobile apps from iTunes App Store and Google Play Store for ED and evaluated different aspects as well as their usage in screening, prevention, management, and their adherence to EAU guidelines. RESULTS: A total of 18 apps were reviewed. All apps are geared towards the patient and provide information about diagnoses and treatment of ED. CONCLUSIONS: MHA represent an integral part of patients' lives, and apps providing services for male sexual dysfunction are constantly increasing. Despite this the overall quality is still low. Although many of these devices are useful in ED, the problems of scientific validation, content, and quality are not yet solved. Further work is needed to improve the quality of apps and developing new accessible, user designed, and high-quality apps.

Male Sexual Dysfunction and Infertility in Spinal Cord Injury Patients: State-of-the-Art and Future Perspectives.

Spinal cord injury (SCI) is a relevant medical and social problem. According to the World Health Organization, the commonly estimated worldwide annual incidence of SCI is 40 to 80 cases per million population. After the SCI experience, most men present with sexual dysfunction (erectile dysfunction (ED) and ejaculatory dysfunction), fertility problems (such as impaired spermatogenesis, abnormalities in sperm viability, motility, and morphology), and systemic disorders such as genitourinary infection and endocrine imbalances. The best options available for managing the ejaculatory disorders in patients suffering from SCI are penile vibratory stimulation (PVS) and electroejaculation (EEJ). Furthermore, the treatment of ED in SCI patients consists of medical therapies including phosphodiesterase 5 inhibitors (PDE5i), intracavernosal injections (ICI), vacuum erection devices (VEDs), and surgical as penile prosthesis (PP). This review provides a snapshot of the current evidence for the mechanisms of sexual dysfunction and infertility in SCI patients, discusses the best management strategies for these conditions, and offers our perspective on the direction of future research.

Prostate Cancer Diagnosis, Treatment and Outcomes in Patients with Previous or Synchronous Colorectal Cancer: A Systematic Review of Published Evidence.

The management of patients with prostate cancer (PCa) and previous or synchronous colorectal cancer (CRC) represents a challenging issue. A systematic review was performed in May 2022 to summarize available evidence about the diagnosis, management, and outcomes of these patients. Twenty-seven studies involving 252 patients were identified. Overall, 163 (64.7%) and 89 (35.3%) patients had synchronous and metachronous PCa and CRC, respectively. In patients with synchronous diseases, PCa treatment involved active surveillance in 1 patient, radical prostatectomy (RP) in 36 patients, radiotherapy (RT) in 60 patients, RP plus RT in 1 patient, proton beam therapy in 1 patient, and cryoablation in 1 patient. In patients with previous CRC treatment, prostate biopsy was mostly performed by transrectal approach (n = 24). The trans-perineal and suprapubic approaches were adopted in 12 and 6 cases, respectively. Surgical PCa treatment in these cases involved endoscopic extraperitoneal RP, robot-assisted RP, and not otherwise specified RP in 30, 15, and 2 cases, respectively. Biochemical recurrence rates ranged from 20% to 28%. Non-surgical PCa treatment options included brachytherapy, RT plus androgen deprivation therapy, and RT alone in 23, 2 and 4 patients, respectively. PCa specific survival was reported by one study and was 100%.

The Role of Testosterone in the Elderly: What Do We Know?

Testosterone is the most important hormone in male health. Aging is characterized by testosterone deficiency due to decreasing testosterone levels associated with low testicular production, genetic factors, adiposity, and illness. Low testosterone levels in men are associated with sexual dysfunction (low sexual desire, erectile dysfunction), reduced skeletal muscle mass and strength, decreased bone mineral density, increased cardiovascular risk and alterations of the glycometabolic profile. Testosterone replacement therapy (TRT) shows several therapeutic effects while maintaining a good safety profile in hypogonadal men. TRT restores normal levels of serum testosterone in men, increasing libido and energy level and producing beneficial effects on bone density, strength and muscle as well as yielding cardioprotective effects. Nevertheless, TRT could be contraindicated in men with untreated prostate cancer, although poor findings are reported in the literature. In addition, different potential side effects, such as polycythemia, cardiac events and obstructive sleep apnea, should be monitored. The aim of our review is to provide an updated background regarding the pros and cons of TRT, evaluating its role and its clinical applicability in different domains.

A Comparative Study of the Triglycerides/HDL Ratio and Pseudocholinesterase Levels in Patients with Bladder Cancer.

BACKGROUND: Lipid alterations may serve as potential tumour biomarkers. The ratio of triglycerides to HDL cholesterol (TG/HDL ratio) is associated with various cancers. Pseudocholinesterase (PChE) activity, involved in TG hydrolysis, plays an important role in the metabolism of lipoprotein. There is scarce data assessing the reliability of both the TG/HDL ratio and PChE levels in correctly classifying patients suffering from bladder cancer. METHODS: Three hundred and ninety-six patients undergoing cystoscopy or transurethral resection of the bladder (TURB), broken into two major groups, i.e., patients with histologically confirmed, non-metastatic bladder cancer (n = 208) and without bladder cancer (no bladder cancer, n = 188), formed the study population. The last group was split into two subgroups consisting of a cohort of patients never suffering from bladder cancer but with other bladder diseases (no CaBD, n = 100) and another cohort formed by patients characterised by eradicated bladder cancer after TURB with no recurrence during a three-month follow-up (previous bladder cancer, n = 88). Pieces of information by both metabolic derangement (the presence of type 2 diabetes mellitus), hypertension and lipid profile were retrieved from patient records upon entry to the study. Sensitivity, specificity, areas under the ROC (AUROC) of the TG/HDL ratio, and PChE levels were used in diagnostic decision making. RESULTS: The TG/HDL ratio as well as PChE concentrations of bladder cancer patients were significantly different when compared to those with previous bladder cancer and the no CaBD patients (p = 0.023 and 0.0004, respectively). There was an independent role of both the TG/HDL ratio and PChE levels in predicting the presence of bladder cancer (OR: 1.22 and 0.99, respectively), but the reliability of the TG/HDL ratio (AUROC: 0.587) was superior to that of PChE levels (AUROC: 0.374). The AUROC of a new parameter resulting from the combination of the TG/HDL ratio with PChE levels showed a further increment in the discriminant power of the bladder cancer presence (0.6298), interestingly with a negative predictive value (89%) according to the Bayesian approach. The cut-off of the TG/HDL ratio, the main marker of the present study that better distinguishes bladder cancer from no bladder cancer patients, was 2.147. DISCUSSION AND CONCLUSIONS: The reliability of the TG/HDL ratio is based on the fact that this parameter likely mirrors the insulin resistance (IR) underlying bladder cancer patients. Furthermore, PChE levels evidence both IR and the associated non-alcoholic fatty liver disease. The TG/HDL ratio and PChE levels as well as their combined use could help physicians to assess/confirm the presence of this very common cancer, where early detection is important to ensure the best therapeutical approach.

Evaluation of PIRs Post-Fire Pull-Out Strength in Concrete Exposed to ISO 834-1 Fire.

Post-installed rebars (PIRs) using mortar can offer bond strength at ambient temperature equal or higher to that of cast-in place rebars. However, high temperatures have the effect of weakening the bond, typically governed by the chemical and physical properties of the mortar which is often sensitive to temperature increase. Therefore, the behavior of PIRs in a fire situation becomes vulnerable. Moreover, after exposure of PIRs to high temperature, the heat transfer continues during the post-fire phase, which might endanger the construction after a fire event. In order to evaluate the evolution of the pull-out capacity during fire, Pinoteau et al. have developed the bond resistance integration method (Pinoteau's RIM) to predict the bond resistance value of a rebar subjected to various temperatures in accordance with the fire exposure curves. Therefore, accurate temperature profiles during the post-fire phase are needed to ensure a correct calculation of the post-fire behavior of the PIR connection. This paper presents 3D finite element thermal simulations of PIRs in concrete exposed to ISO 834-1 fire conditions then cooled with ambient air. Numerical thermal profiles are then compared to the experimental results (i.e., post-fire pull-out tests). The proposed model provides guidelines for conducting numerical simulations to determine the thermal entry data necessary for predicting thermal profiles in PIRs during heating and cooling phases. Then, the post-fire pull-out capacity of PIRs in concrete is calculated using Pinoteau's RIM, and compared to experimental post-fire pull-out results.

Modulation of aldose reductase activity by aldose hemiacetals.

BACKGROUND: Glucose is considered as one of the main sources of cell damage related to aldose reductase (AR) action in hyperglycemic conditions and a worldwide effort is posed in searching for specific inhibitors of the enzyme. This AR substrate has often been reported as generating non-hyperbolic kinetics, mimicking a negative cooperative behavior. This feature was explained by the simultaneous action of two enzyme forms acting on the same substrate. METHODS: The reduction of different aldoses and other classical AR substrates was studied using pure preparations of bovine lens and human recombinant AR. RESULTS: The apparent cooperative behavior of AR acting on glucose and other hexoses and pentoses, but not on tethroses, glyceraldehyde, 4-hydroxynonenal and 4-nitrobenzaldehyde, is generated by a partial nonclassical competitive inhibition exerted by the aldose hemiacetal on the reduction of the free aldehyde. A kinetic model is proposed and kinetic parameters are determined for the reduction of l-idose. CONCLUSIONS: Due to the unavoidable presence of the hemiacetal, glucose reduction by AR occurs under different conditions with respect to other relevant AR-substrates, such as alkanals and alkenals, coming from membrane lipid peroxidation. This may have implications in searching for AR inhibitors. The emerging kinetic parameters for the aldoses free aldehyde indicate the remarkable ability of the enzyme to interact and reduce highly hydrophilic and bulky substrates. GENERAL SIGNIFICANCE: The discovery of aldose reductase modulation by hemiacetals offers a new perspective in searching for aldose reductase inhibitors to be developed as drugs counteracting the onset of diabetic complications.