Add-on effects of Chinese herbal medicine external application (FZHFZY) to topical urea for mild-to-moderate psoriasis vulgaris: Protocol for a double-blinded randomized controlled pilot trial embedded with a qualitative study.

Psoriasis vulgaris is a chronic dermatological disease with a high global prevalence. It significantly reduces patients' quality of life and is associated with a substantial economic burden. Conventional therapies for mild-to-moderate psoriasis are often associated with insufficient long-term symptomatic relief and side effects. Chinese herbal medicine (CHM) is commonly used for psoriasis management. A CHM formula, namely Fu zheng he fu zhi yang (FZHFZY), has shown promising treatment effects in clinical practice when used as a bath therapy. However, its efficacy and safety has not been evaluated by a rigorous randomized controlled trial (RCT). Therefore, we designed a double-blinded pilot RCT embedded with a qualitative study on CHM formula FZHFZY plus topical urea for mild-to-moderate psoriasis vulgaris to advance the evidence development and practice of CHM external application for psoriasis. This will be a mixed-method design consisting of a pilot RCT and a qualitative study. The pilot RCT is a two-arm, parallel, placebo-controlled, double-blinded trial. Sixty eligible participants will be randomized at a 1:1 ratio to receive eight weeks' treatment of either FZHFZY plus 10% urea cream, or placebo plus 10% urea cream, with 12-week follow-up visits after the treatment phase. The CHM or placebo will be administered externally as a bath therapy. Outcome measures include trial feasibility, efficacy and safety. The primary efficacy outcome will be Psoriasis Area Severity Index (PASI). Secondary efficacy outcomes include Physician Global Assessment, PASI-75, PASI-50, Body Surface Area, Dermatology Life Quality Index, Skindex-16, itch visual analogue scale and relapse. The qualitative study will be conducted to collect participants' feedback on CHM external application and their experience with the pilot RCT. This study will advance the evidence-based clinical practice of using CHM for psoriasis vulgaris and then to support translation of findings into clinical practice in the future. Trial registration number: ChiCTR2200064092.

Parkinson's disease psychosis management: an evidence based, experience informed, pragmatic approach.

INTRODUCTION: Psychotic symptoms in people with Parkinson's disease (PD) have attracted increasing. Recommendations on treating psychosis often fail to take into account what psychotic symptoms require treatment, which has been complicated by the increasing number of reports documenting the frequency of 'minor' hallucinations. AREAS COVERED: This article focuses both on the phenomenology of psychotic symptoms and their management. EXPERT OPINION: Understanding the nature and implications of the types of psychotic symptoms in PD is the key to proper treatment. Evidence and experience-based data on the effect of anti-psychotic medications will be reviewed and how the various clinical settings should determine the treatment approach. The evidence base consists of all reported blinded trials recorded in PubMed and the experience-based studies are those chosen by the author from PubMed as illustrative. Specific recommendations for the treatment of psychosis will be listed for specific situations. Pimavanserin is the first-line choice for mild symptoms; quetiapine for symptoms that require improvement in a short period and clozapine for urgent problems or those which fail the other approaches.

Psychotic symptoms are common in PD, affecting the majority of patients by the time of death. 'Minor hallucinations' rarely require treatment but formed hallucinations and delusions often do. The vast majority of patients requiring treatment are on medications for PD motor problems. Some patients can be treated with reduction of psychoactive medications that are unrelated to PD, and some may tolerate reductions in PD medications without intolerable worsening of motor function. The remainder require treatment with medications that reduce psychotic symptoms, which include cholinesterase inhibitors, clozapine, pimavanserin, and possibly quetiapine and electroconvulsive therapy. Only clozapine and pimavanserin have unequivocal evidence for efficacy and motor tolerance. Data will be reviewed in support of each of these medications will be reviewed and pragmatic suggestions based on a large experience on when each might be used, and in what order they may be tried if initial approaches fail.

Mitochondrial targets in hyperammonemia: Addressing urea cycle function to improve drug therapies.

The urea cycle (UC) is a critically important metabolic process for the disposal of nitrogen (ammonia) produced by amino acids catabolism. The impairment of this liver-specific pathway induced either by primary genetic defects or by secondary causes, namely those associated with hepatic disease or drug administration, may result in serious clinical consequences. Urea cycle disorders (UCD) and certain organic acidurias are the major groups of inherited rare diseases manifested with hyperammonemia (HA) with UC dysregulation. Importantly, several commonly prescribed drugs, including antiepileptics in monotherapy or polytherapy from carbamazepine to valproic acid or specific antineoplastic agents such as asparaginase or 5-fluorouracil may be associated with HA by mechanisms not fully elucidated. HA, disclosing an imbalance between ammoniagenesis and ammonia disposal via the UC, can evolve to encephalopathy which may lead to significant morbidity and central nervous system damage. This review will focus on biochemical mechanisms related with HA emphasizing some poorly understood perspectives behind the disruption of the UC and mitochondrial energy metabolism, namely: i) changes in acetyl-CoA or NAD+ levels in subcellular compartments; ii) post-translational modifications of key UC-related enzymes, namely acetylation, potentially affecting their catalytic activity; iii) the mitochondrial sirtuins-mediated role in ureagenesis. Moreover, the main UCD associated with HA will be summarized to highlight the relevance of investigating possible genetic mutations to account for unexpected HA during certain pharmacological therapies. The ammonia-induced effects should be avoided or overcome as part of safer therapeutic strategies to protect patients under treatment with drugs that may be potentially associated with HA.

Discovery of 6-Formylpyridyl Urea Derivatives as Potent Reversible-Covalent Fibroblast Growth Factor Receptor 4 Inhibitors with Improved Anti-Hepatocellular Carcinoma Activity.

Fibroblast growth factor receptor 4 (FGFR4) has been considered as a potential anticancer target due to FGF19/FGFR4 mediated aberrant signaling in hepatocellular carcinoma (HCC). Several FGFR4 inhibitors have been reported, but none have gained approval. Herein, a series of 5-formyl-pyrrolo[3,2-b]pyridine-3-carboxamides and a series of 6-formylpyridyl ureas were characterized as selective reversible-covalent FGFR4 inhibitors. The representative 6-formylpyridyl urea 8z exhibited excellent potency against FGFR4WT, FGFR4V550L, and FGFR4V550M with IC50 values of 16.3, 12.6, and 57.3 nM, respectively. It also potently suppressed proliferation of Ba/F3 cells driven by FGFR4WT, FGFR4V550L, and FGFR4V550M, and FGFR4-dependent Hep3B and Huh7 HCC cells, with IC50 values of 1.2, 13.5, 64.5, 15.0, and 20.4 nM, respectively. Furthermore, 8z displayed desirable microsomal stability and significant in vivo efficacy in the Huh7 HCC cancer xenograft model in nude mice. The study provides a promising new lead for anticancer drug discovery directed toward overcoming FGFR4 gatekeeper mutation mediated resistance in HCC patients.

Efectividad de la administración de urea para el tratamiento de la hiponatremia en la insuficiencia cardiaca / Effectiveness of urea administration for the treatment of hyponatremia in heart failure

Objetivos Valorar la eficacia y la seguridad de la urea en pacientes con hiponatremia e insuficiencia cardiaca (IC). Métodos y resultados Se trata de un estudio observacional retrospectivo analítico de pacientes con IC e hiponatremia (Na+ <135mmol/l). Se incluyeron 49 pacientes tratados con urea y 47 pacientes que no recibieron urea, todos ellos bajo tratamiento estándar (según práctica clínica habitual) de la IC, con seguimiento en el hospital Álvaro Cunqueiro de Vigo entre enero de 2013 y mayo de 2022. En el estudio se evaluó la normalización de los niveles de sodio (Na >135mmol/l). La natremia al inicio del tratamiento con urea oral era de 127±5,22mmol/l, a las 24horas el sodio era de 128±2,47 (p<0,009) y la media el día de la normalización fue de 135,19±4,23mmol/l (p<0,005). Los días de media para conseguir la normalización del sodio fueron 5,03±2,37. La uremia al inicio del tratamiento con urea era de 73±46,93mg/dl y la media el día de la normalización del Na+ fue de 116,05±63,64mg/dl (p<0,002). La dosis media de urea oral fue 22,5g/día. No se observaron efectos adversos relevantes, ni cambios en cuanto a las cifras de creatinina. Conclusiones El tratamiento con urea oral añadido al tratamiento estándar, durante cortos periodos de tiempo, es seguro y eficaz para corregir la natremia en pacientes con IC hipervolémica con hiponatremia.

Objectives To assess the efficacy and safety of urea in patients with hyponatremia and heart failure (HF). Methods and results This is a retrospective observational analytical study of patients with HF and hyponatremia (Na+ <135mmol/L). Forty-nine patients treated with urea and 47 patients who did not receive urea, all under standard treatment (according to usual clinical practice) for HF, were included and followed up at Álvaro Cunqueiro Hospital in Vigo (Spain) between January 2013 and May 2022. The study evaluated the normalization of sodium levels (Na >135mmol/L). The initial natremia at the start of oral urea treatment was 127±5.22 mmol/L, at 24h the sodium level was 128±2.47 (P<.009), and the mean on the day of normalization was 135.19±4.23mmol/L (P<.005). The average number of days to achieve sodium normalization was 5.03±2.37 days. The initial uremia at the start of urea treatment was 73±46.93mg/dL, and the mean on the day of Na+ normalization was 116.05±63.64mg/dL (P<.002). The average oral urea dose was 22.5g/day. No relevant adverse effects were observed, nor were there significant changes in creatinine levels. Conclusions Oral urea treatment, when added to standard treatment for short periods of time, is safe and effective in correcting natremia in patients with hypervolemic HF with hyponatremia. (AU)

Efectividad de la administración de urea para el tratamiento de la hiponatremia en la insuficiencia cardiaca / Effectiveness of urea administration for the treatment of hyponatremia in heart failure

Objetivos Valorar la eficacia y la seguridad de la urea en pacientes con hiponatremia e insuficiencia cardiaca (IC). Métodos y resultados Se trata de un estudio observacional retrospectivo analítico de pacientes con IC e hiponatremia (Na+ <135mmol/l). Se incluyeron 49 pacientes tratados con urea y 47 pacientes que no recibieron urea, todos ellos bajo tratamiento estándar (según práctica clínica habitual) de la IC, con seguimiento en el hospital Álvaro Cunqueiro de Vigo entre enero de 2013 y mayo de 2022. En el estudio se evaluó la normalización de los niveles de sodio (Na >135mmol/l). La natremia al inicio del tratamiento con urea oral era de 127±5,22mmol/l, a las 24horas el sodio era de 128±2,47 (p<0,009) y la media el día de la normalización fue de 135,19±4,23mmol/l (p<0,005). Los días de media para conseguir la normalización del sodio fueron 5,03±2,37. La uremia al inicio del tratamiento con urea era de 73±46,93mg/dl y la media el día de la normalización del Na+ fue de 116,05±63,64mg/dl (p<0,002). La dosis media de urea oral fue 22,5g/día. No se observaron efectos adversos relevantes, ni cambios en cuanto a las cifras de creatinina. Conclusiones El tratamiento con urea oral añadido al tratamiento estándar, durante cortos periodos de tiempo, es seguro y eficaz para corregir la natremia en pacientes con IC hipervolémica con hiponatremia.

Objectives To assess the efficacy and safety of urea in patients with hyponatremia and heart failure (HF). Methods and results This is a retrospective observational analytical study of patients with HF and hyponatremia (Na+ <135mmol/L). Forty-nine patients treated with urea and 47 patients who did not receive urea, all under standard treatment (according to usual clinical practice) for HF, were included and followed up at Álvaro Cunqueiro Hospital in Vigo (Spain) between January 2013 and May 2022. The study evaluated the normalization of sodium levels (Na >135mmol/L). The initial natremia at the start of oral urea treatment was 127±5.22 mmol/L, at 24h the sodium level was 128±2.47 (P<.009), and the mean on the day of normalization was 135.19±4.23mmol/L (P<.005). The average number of days to achieve sodium normalization was 5.03±2.37 days. The initial uremia at the start of urea treatment was 73±46.93mg/dL, and the mean on the day of Na+ normalization was 116.05±63.64mg/dL (P<.002). The average oral urea dose was 22.5g/day. No relevant adverse effects were observed, nor were there significant changes in creatinine levels. Conclusions Oral urea treatment, when added to standard treatment for short periods of time, is safe and effective in correcting natremia in patients with hypervolemic HF with hyponatremia. (AU)

Murine Malaria Model: Ketoconazole Prevented Malaria while Proguanil and Sulfadoxine/Pyrimethamine Protected against Malaria-associated Anemia and Kidney Damage.

BACKGROUND: The concern about the global spread of resistant malaria has made the researchers not focus only on the treatment of established infections but relatively more on the prevention of the disease. OBJECTIVE: This study evaluates the chemopreventive activity of ketoconazole in a murine malarial model. METHOD: Five out of seven groups of mice were pretreated for five days with proguanil (PRG), sulfadoxine/ pyrimethamine (SP), 10, 20, and 40 mg/kg body weight (b.w) of ketoconazole (KET10, KET20, and KET40), before being infected (on the sixth day) with Plasmodium berghei. Two other groups were infected-not-treated (INT) and not-infected-nor-treated (NINT). At 72 hours postinfection, five out of ten mice in each group were sacrificed to assess parasitemia, chemoprevention, hematologic, hepatic, and renal parameters. The remaining mice were observed for 28 days to determine their mean survival day post-infection (SDPI). RESULTS: All ketoconazole groups, except KET10, demonstrated 100% chemoprevention and significantly higher mean SDPI (p<0.001) in relation to INT (negative control). There was no significant difference in the mean SDPI observed in KET20 in relation to PRG or NINT (healthy control). A dose-related increase (p<0.01) in the mean plasma urea was observed when ketoconazole groups were compared to one another: KET10 versus KET20 (p<0.01) and KET20 versus KET40 (p<0.01). Sulfadoxine/pyrimethamine demonstrated significantly reduced mean plasma urea (p<0.001) and creatinine (p<0.05) in relation to INT and NINT, respectively. While PRG demonstrated significantly higher mean red blood cell (RBC), hemoglobin (HGB), and hematocrit (HCT) in relation to INT. CONCLUSION: Ketoconazole possesses prophylactic antimalarial activity with associated dose-related renal impairment. Sulfadoxine/pyrimethamine demonstrated renoprotective potentials, while PRG prevented malaria-associated anemia.

[Effectiveness of urea administration for the treatment of hyponatremia in heart failure]. / Efectividad de la administración de urea para el tratamiento de la hiponatremia en la insuficiencia cardiaca.

OBJECTIVES: To assess the efficacy and safety of urea in patients with hyponatremia and heart failure (HF). METHODS AND RESULTS: This is a retrospective observational analytical study of patients with HF and hyponatremia (Na+ <135mmol/L). Forty-nine patients treated with urea and 47 patients who did not receive urea, all under standard treatment (according to usual clinical practice) for HF, were included and followed up at Álvaro Cunqueiro Hospital in Vigo (Spain) between January 2013 and May 2022. The study evaluated the normalization of sodium levels (Na >135mmol/L). The initial natremia at the start of oral urea treatment was 127±5.22 mmol/L, at 24h the sodium level was 128±2.47 (P<.009), and the mean on the day of normalization was 135.19±4.23mmol/L (P<.005). The average number of days to achieve sodium normalization was 5.03±2.37 days. The initial uremia at the start of urea treatment was 73±46.93mg/dL, and the mean on the day of Na+ normalization was 116.05±63.64mg/dL (P<.002). The average oral urea dose was 22.5g/day. No relevant adverse effects were observed, nor were there significant changes in creatinine levels. CONCLUSIONS: Oral urea treatment, when added to standard treatment for short periods of time, is safe and effective in correcting natremia in patients with hypervolemic HF with hyponatremia.

Transition to glycerol phenylbutyrate for the management of urea cycle disorders: clinical experiences.

BACKGROUND: Urea cycle disorders (UCDs) are a group of rare inborn diseases caused by a deficiency in one of the six enzymes or one of the two transporters involved in the urea cycle. The most common biochemical feature is elevated blood ammonia levels, which can be toxic at high levels, especially to the brain and may manifest as encephalopathy if left untreated. Glycerol phenylbutyrate (GPB) is currently approved for use in the USA and Europe for patients of all ages with UCD who cannot be managed with protein restriction and/or amino acid supplementation alone. This article presents the author's experience in different exemplary settings and depicts the most efficient management of UCDs with GPB. CASE PRESENTATION: Six patient histories are described. 4 had OCT, one citrullinemia, and one argininosuccinic aciduria. Treatment with GPB was started between 2 days and 14 years of age. Before GPB, one patient had not been treated, 4 had received sodium phenylbutyrate (NaPB), and one Na benzoate. CONCLUSIONS: Overall, treatment with GPB was followed by a relevant metabolic improvement, resulting in better therapeutic compliance, reduced hospitalization, and improved quality of life.

Protective effect of activated charcoal against progression of chronic kidney disease: A randomized clinical study.

Chronic kidney disease (CKD) is a non-reversible and progressive disease affecting the kidneys, significantly impacting global public health. One of the complications of chronic kidney disease is impaired intestinal barrier function, which may allow harmful products such as urea to enter the bloodstream and cause systemic inflammation. This study aimed to investigate whether supplementation with activated charcoal could reduce uremic toxins in patients with end-stage renal disease (ESRD). The study was a randomized clinical trial conducted at the Dialysis Center of al Diwaniyah Medical Hospital in the Diwaniyah Governorate. Eighty-two patients with ESRD on regular hemodialysis were enrolled, with 15 patients receiving oral supplementation with activated charcoal in addition to standard care and 13 patients receiving only standard care. Blood samples were collected at baseline and after eight weeks, and several biomarkers were measured, including estimated glomerular filtration rate (eGFR), creatinine, urea, phosphorus, albumin, and indoxyl sulfate. The results showed a significant reduction in both serum urea and serum phosphorus levels after eight weeks of oral-activated charcoal treatment. However, the other biomarkers were not affected by the treatment. In conclusion, the use of oral-activated charcoal for eight weeks in Iraqi patients undergoing maintenance hemodialysis improved urea and phosphorus levels.

Ammonia scavenger and glutamine synthetase inhibitors cocktail in targeting mTOR/ß-catenin and MMP-14 for nitrogen homeostasis and liver cancer.

The glutamine synthetase (GS) facilitates cancer cell growth by catalyzing de novo glutamine synthesis. This enzyme removes ammonia waste from the liver following the urea cycle. Since cancer development is associated with dysregulated urea cycles, there has been no investigation of GS's role in ammonia clearance. Here, we demonstrate that, although GS expression is increased in the setting of ß-catenin oncogenic activation, it is insufficient to clear the ammonia waste burden due to the dysregulated urea cycle and may thus be unable to prevent cancer formation. In vivo study, a total of 165 male Swiss albino mice allocated in 11 groups were used, and liver cancer was induced by p-DAB. The activity of GS was evaluated along with the relative expression of mTOR, ß-catenin, MMP-14, and GS genes in liver samples and HepG2 cells using qRT-PCR. Moreover, the cytotoxicity of the NH3 scavenger phenyl acetate (PA) and/or GS-inhibitor L-methionine sulfoximine (MSO) and the migratory potential of cells was assessed by MTT and wound healing assays, respectively. The Swiss target prediction algorithm was used to screen the mentioned compounds for probable targets. The treatment of the HepG2 cell line with PA plus MSO demonstrated strong cytotoxicity. The post-scratch remaining wound area (%) in the untreated HepG2 cells was 2.0%. In contrast, the remaining wound area (%) in the cells treated with PA, MSO, and PA + MSO for 48 h was 61.1, 55.8, and 78.5%, respectively. The combination of the two drugs had the greatest effect, resulting in the greatest decrease in the GS activity, ß-catenin, and mTOR expression. MSO and PA are both capable of suppressing mTOR, a key player in the development of HCC, and MMP-14, a key player in the development of HCC. PA inhibited the MMP-14 enzyme more effectively than MSO, implying that PA might be a better way to target HCC as it inhibited MMP-14 more effectively than MSO. A large number of abnormal hepatocytes (5%) were found to be present in the HCC mice compared to mice in the control group as determined by the histopathological lesions scores. In contrast, PA, MSO, and PA + MSO showed a significant reduction in the hepatic lesions score either when protecting the liver or when treating the liver. The molecular docking study indicated that PA and MSO form a three-dimensional structure with NF-κB and COX-II, blocking their ability to promote cancer and cause gene mutations. PA and MSO could be used to manipulate GS activities to modulate ammonia levels, thus providing a potential treatment for ammonia homeostasis.

[The efficiency of pre-administration of a peptide mimicking the spatial structure of erythropoietin -chain B in modeling experimental post-contrast acute kidney injury].

AIM: To study the efficiency of pre-administration of a peptide mimicking the spatial structure of erythropoietin -chain B in modeling experimental post-contrast acute kidney injury. MATERIALS AND METHODS: In this study, an experimental model of post-contrast acute kidney injury was created using a non-steroidal anti-inflammatory drug, a nitric oxide synthase inhibitor, and injection of iopromide to mature male mice. After 48 hours, a comprehensive assessment of the concentration of creatinine, urea, glomerular filtration rate, the ratio of urea/albumin in the serum, as well as the level of proteinuria and interleukin 6 in the urine was carried out. RESULTS: A peptide mimicking the spatial structure of erythropoietin -chain B, administered at a dose of 100 g/kg 30 minutes before modeling of pathologic process, contributes to a significant decrease in creatinine and urea concentrations by 2.5 and 1.8 times, respectively, with an increase in glomerular filtration rate 4.4 times. In addition, in the group with pharmacological correction, there was a significant decrease in the ratio of urea/albumin by 2.2 times, a decrease in the level of proteinuria by 61.9% and a decrease in the concentration of pro-inflammatory interleukin-6 in the urine by 2.1 times. CONCLUSION: Thus, the preliminary administration of a peptide that mimics the spatial structure of the erythropoietin -chain B helps to reduce the severity of post-contrast acute kidney injury in the experiment, due to anti-inflammatory properties.

The potential renoprotective effect of Raloxifene in renal ischemia-reperfusion injury in a male rat model.

Renal ischemia-reperfusion injury is caused by a temporary reduction in oxygen-carrying blood flow to the kidney, followed by reperfusion. During ischemia, kidney tissue damage induces overproduction of reactive oxygen species, which produces oxidative stress. The blood flow restoration during the reperfusion period causes further production of reactive oxygen species that ends with apoptosis and cell death. This study aimed to investigate the potential renoprotective effects of Raloxifene on bilateral renal ischemia-reperfusion injury in rats by looking into kidney function biomarkers, urea and creatinine, inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß). Additionally, antioxidant markers such as total antioxidant capacity (TAC) and the pro-apoptotic marker caspase-3 were assessed. Histopathological scores were also employed for evaluation. Our experimental design involved 20 rats divided into four groups: the sham group underwent median laparotomy without ischemia induction, the control group experienced bilateral renal ischemia for 30 minutes followed by 2 hours of reperfusion, the vehicle group received pretreatment with a mixture of corn oil and dimethyl sulfoxide (DMSO) before ischemia induction, and the Raloxifene-treated group was administered Raloxifene at a dose of 10 mg/kg before ischemia induction, followed by ischemia-reperfusion. Urea and creatinine, TNF-α, IL-1ß, and caspase-3 in the Raloxifene group were significantly lower compared to the control and vehicle groups. On the other hand, TAC levels in the Raloxifene group were significantly higher than in the control and vehicle groups. This study concluded that Raloxifene had a renoprotective impact via multiple actions as an anti-inflammatory, anti-apoptotic, and antioxidant agent.

Use of Urea for the Syndrome of Inappropriate Secretion of Antidiuretic Hormone: A Systematic Review.

Importance: Hyponatremia and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) are associated with significant mortality and morbidity. The effectiveness and safety of oral urea for SIADH are still debated. Objective: To evaluate the efficacy and safety of urea for the treatment of SIADH. Evidence Review: A systematic search of Medline and Embase was conducted for controlled and uncontrolled studies of urea for SIADH in adult patients. The primary outcome was serum sodium concentration after treatment. Secondary outcomes included the proportion of patients with osmotic demyelination syndrome (ODS), intracranial pressure, and resource use such as length of stay. Findings: Twenty-three studies involving 537 patients with SIADH were included, of which 462 were treated with urea. The pooled mean baseline serum sodium was 125.0 mmol/L (95% CI, 122.6-127.5 mmol/L). The median treatment duration with oral urea was 5 days. Urea increased serum sodium concentration by a mean of 9.6 mmol/L (95% CI, 7.5-11.7 mmol/L). The mean increase in serum sodium after 24 hours was 4.9 mmol/L (95% CI, 0.5-9.3 mmol/L). Adverse events were few, mainly consisting of distaste or dysgeusia, and no case of ODS was reported. Resource use was too infrequently reported to be synthesized. Conclusions and Relevance: In this systematic review of the use of urea in SIADH and despite the lack of randomized clinical trials, lower-quality evidence was identified that suggests that urea may be an effective, safe, and inexpensive treatment modality that warrants further exploration.

Dental aesthetic perception of patients submitted to activated charcoal-based bleaching agents: A randomized clinical trial.

OBJECTIVE: To evaluate the effects of activated charcoal-based products used in two presentation forms (powder or toothpaste), compared to 10 % carbamide peroxide and conventional toothpaste on aesthetic perception and psychosocial impact before and after treatment. METHODS: Fifty-six participants were divided into 4 experimental groups (n = 14). Activated charcoal-based powder (PW); Activated charcoal-based dentifrice (AC); Conventional fluoride toothpaste (CD) and 10 % carbamide peroxide (CP). All products were used for 14 days. Psychosocial impact on dental esthetics (PIDAQ), oral health impact profile (OHIP- Esthetics) and orofacial esthetics scale (OES) questionnaires were applied before and after treatment. Descriptive and exploratory data analyses were performed and analyzed using linear mixed models for repeated measures over time considering significance level of α = 0.05. RESULTS: For PIDAQ, the CP group showed significant decrease in psychological impact, aesthetic perception domains and overall score, while in the PW group, there was only a significant decrease in the psychological impact domain. Decrease in OHIP was observed for the functional limitation domain scores for treatments with CP and PW, in the psychological discomfort domain, decrease was observed for all groups, while for the OES questionnaire, significant increase in the color domain was observed for the CP group. CONCLUSION: Activated charcoal-based products showed lower scores in all questionnaires when compared with carbamide peroxide; thus, charcoal-based products promoted lower impact on quality of life and aesthetic perception. CLINICAL RELEVANCE: In this randomized clinical trial, charcoal-based OTC products had inferior quality of life and aesthetic perception results compared to conventional carbamide peroxide bleaching.

Mechanisms of landiolol-mediated positive inotropy in critical care settings.

PURPOSE: To present the potential mechanisms by which landiolol enhances a positive inotropic response in critically ill patients. METHODS: Analysis of preclinical, animal, and clinical data to provide novel knowledge and translate research findings into potential clinical application. RESULTS: The super-selective ß1-antagonist landiolol may increase inotropy and may be associated with positive outcomes in critically ill patients with acute decompensated heart failure or sepsis. CONCLUSION: This review sheds light on the potential mechanisms by which landiolol enhances a positive inotropic response, potentially alleviating the long-held concern over possible negative hemodynamic effects in critically ill patients.

Effect of bleaching treatments on the adhesion of orthodontic brackets: a systematic review.

BACKGROUND: Nowadays bleaching procedures have gained popularity in orthodontic patients. Peroxide and Carbamide acids are the common agents which are used in in-office and at home bleaching techniques. Consequently, the Bonding adhesion to the enamel can be influenced by the orthodontic phase and the residual peroxide might interfere with the polymerization and the adhesion of the brackets. Frequent debonding of the brackets from teeth after the bleaching procedure could cause the lengthening of the therapy and promote irregularities on enamel surface derived from an additional bonding phase of the brackets. The aim of this systematic review is to appraise the influence regarding the effect of the bleaching procedure on the bond strength of orthodontic brackets. METHODS: An electronic database search was performed. Search terms included: bleaching, brackets, adhesion; data were extracted and summarized. Risk of bias was assessed using the Chocrane risk of bias tool, adapted for in vitro studies. RESULTS: A total of 8689 articles were screened and 11 studies met the inclusion criteria of this systematic review. 1000 teeth of human and bovine origin were analyzed for the shear bond strength (SBS) of stainless and ceramic brackets after the bleaching treatments. All the authors divided the groups in different subgroups with different bleaching agents and in different concentration. The SBS value allowed to demonstrate the necessity to delay the bonding of the brackets for two weeks after a bleaching treatment and its improvement when tooth mousse or antioxidants agents are used. CONCLUSIONS: The SBS values and the delay of the bonding procedure must be considered in dental practice and clinical strategies are necessary in order to avoid drawbacks which could cause the debonding of the brackets after bleaching due to the alterations of the dental substrate, thus interfering with the orthodontic treatments.