RESUMO

INTRODUCTION: The efficacy of liraglutide for treating type 2 diabetes mellitus and obesity is well established, but their role in the treatment of weight regain after bariatric surgery remains unclear. METHODS: We searched PubMed, Embase, and Cochrane Library databases in January 2024. A random-effects model was employed to compute mean differences (MD) and events per 100 observations with 95% confidence intervals (CI) for continuous and binary endpoints. Statistical analysis was performed using R software. RESULTS: A total of 16 studies were included and 881 individuals. Patients were mostly female (50%), aged 36 to 55 years, with a mean body mass index (BMI) of 39.4 kg/m2, and had BS surgery 5 years prior. Over a mean follow-up time ranging from 3 months to 4 years, it was observed a statistically significant reduction in BMI (MD - 8.56 kg/m2; 95% CI 3.34 to 13.79; p < 0.01) and a mean reduction in total weight (MD - 16.03 kg; 95% CI 0.03 to 32.02; p = 0.05) after liraglutide use. Additionally, 65% of patients undertaking liraglutide showed total body weight loss (BWL) above 5% (65.8 events per 100 observations; 95% CI 54.96 to 75.20; p < 0.01), while 26% lost more than 10% of total BWL (26.77 events per 100 observations; 95% CI 19.17 to 36.02; p < 0.01). A limitation is a variability between the studies. CONCLUSIONS: Our findings support the use of liraglutide for weight management in patients who experience weight regain after BS. Liraglutide is well tolerated and promotes significant weight loss, providing clinicians with a therapeutic option for this clinical challenge.

Assuntos

RESUMO

BACKGROUND: Dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist with sedative and analgesic effects, has been suggested in recent studies to possess renoprotective properties. Dexmedetomidine may reduce the incidence of delayed graft function and contribute to effective pain control post-renal transplantation. The primary objective of this systematic review was to assess whether dexmedetomidine decreases the occurrence of delayed graft function in renal transplant patients. METHODS: Databases including MEDLINE, EMBASE, and CENTRAL were comprehensively searched from their inception until March 2023. The inclusion criteria covered all Randomized Clinical Trials (RCTs) and observational studies comparing dexmedetomidine to control in adult patients undergoing renal transplant surgery. Exclusions comprised case series and case reports. RESULTS: Ten RCTs involving a total of 1358 patients met the eligibility criteria for data synthesis. Compared to the control group, the dexmedetomidine group demonstrated a significantly lower incidence of delayed graft function (OR = 0.71, 95% CI 0.52-0.97, p = 0.03, GRADE: Very low, I2 = 0%). Dexmedetomidine also significantly prolonged time to initiation of rescue analgesia (MD = 6.73, 95% CI 2.32-11.14, p = 0.003, GRADE: Very low, I2 = 93%) and reduced overall morphine consumption after renal transplant (MD = -5.43, 95% CI -7.95 to -2.91, p < 0.0001, GRADE: Very low, I2 = 0%). The dexmedetomidine group exhibited a significant decrease in heart rate (MD = -8.15, 95% CI -11.45 to -4.86, p < 0.00001, GRADE: Very low, I2 = 84%) and mean arterial pressure compared to the control group (MD = -6.66, 95% CI -11.27 to -2.04, p = 0.005, GRADE: Very low, I2 = 87%). CONCLUSIONS: This meta-analysis suggests that dexmedetomidine may potentially reduce the incidence of delayed graft function and offers a superior analgesia profile as compared to control in adults undergoing renal transplants. However, the high degree of heterogeneity and inadequate sample size underscore the need for future adequately powered trials to confirm these findings.

RESUMO

Background: The anti-inflammatory effect could be one of the mechanisms by which semaglutide reduces cardiovascular risk in patients with type 2 diabetes mellitus (T2DM) and/or obesity. Determining the anti-inflammatory effect of semaglutide was the objective of this systematic review and meta-analysis. Methods: This meta-analysis was performed according to the PRISMA guidelines. A literature search was performed to detect randomised clinical trials that have quantified the effect of semaglutide on C-reactive protein (CRP) levels compared to placebo or a control group (other glucose-lowering drugs). The primary outcome was CRP index (final CRP/basal CRP). A random-effects model was used. Results: Thirteen randomised clinical trials were considered eligible (n = 26,131). Overall, semaglutide therapy was associated with lower CRP index values compared to the placebo group (SMD -0.56; 95% CI -0.69 to -0.43, I 2 92%) or the control group (SMD -0.45; 95% CI -0.68 to -0.23, I 2 82%).Such an association was similarly observed when different treatment regimens (subcutaneous vs. oral) or different populations (patients with or without T2DM) were analysed. The sensitivity analysis showed that the results were robust. Conclusion: The present meta-analysis demonstrated that the use of semaglutide was associated with a reduction in inflammation irrespective of the population evaluated or the treatment regimen used. These findings would explain one of the mechanisms by which semaglutide reduces cardiovascular events. Systematic Review Registration: PROSPERO [CRD42024500551].

RESUMO

Monotherapy is the recommended initial treatment for early Parkinson's disease. The pharmacological options for initial treatment include dopaminergic agonists, monoamine oxidase B inhibitors, and levodopa formulations. Several factors should be considered when selecting the optimal treatment, such as disease severity, disease duration, age, activity level, and the risk of developing motor and non-motor complications. Early evidence on the potential role of levodopa formulations in the risk of dyskinesia led to levodopa aversion in the late 1990s and early 2000s, favoring the use of levodopa-sparing options like dopamine agonists. This shift resulted in an increase in behavioral adverse effects, such as impulse control disorders, leading to a subsequent dopamine agonist aversion in the mid-2000s. This review aims to provide a comprehensive evaluation of the existing literature regarding the benefits and drawbacks of levodopa versus levodopa-sparing strategies in drug-naive early-stage Parkinson's disease.

Assuntos

RESUMO

Parkinson's disease (PD) is a gradually worsening neurodegenerative disorder affecting the nervous system, marked by a slow progression and varied symptoms. It is the second most common neurodegenerative disease, affecting over six million people in the world. Its multifactorial etiology includes environmental, genomic, and epigenetic factors. Clinical symptoms consist of non-motor and motor symptoms, with motor symptoms being the classic presentation. Therapeutic approaches encompass pharmacological, non-pharmacological, and surgical interventions. Traditional pharmacological treatment consists of administering drugs (MAOIs, DA, and levodopa), while emerging evidence explores the potential of antidiabetic agents for neuroprotection and gene therapy for attenuating parkinsonian symptoms. Non-pharmacological treatments, such as exercise, a calcium-rich diet, and adequate vitamin D supplementation, aim to slow disease progression and prevent complications. For those patients who have medically induced side effects and/or refractory symptoms, surgery is a therapeutic option. Deep brain stimulation is the primary surgical option, associated with motor symptom improvement. Levodopa/carbidopa intestinal gel infusion through percutaneous endoscopic gastrojejunostomy and a portable infusion pump succeeded in reducing "off" time, where non-motor and motor symptoms occur, and increasing "on" time. This article aims to address the general aspects of PD and to provide a comparative comprehensive review of the conventional and the latest therapeutic advancements and emerging treatments for PD. Nevertheless, further studies are required to optimize treatment and provide suitable alternatives.

Assuntos

RESUMO

ABSTRACT Monotherapy is the recommended initial treatment for early Parkinson´s disease. The pharmacological options for initial treatment include dopaminergic agonists, monoamine oxidase B inhibitors, and levodopa formulations. Several factors should be considered when selecting the optimal treatment, such as disease severity, disease duration, age, activity level, and the risk of developing motor and non-motor complications. Early evidence on the potential role of levodopa formulations in the risk of dyskinesia led to levodopa aversion in the late 1990s and early 2000s, favoring the use of levodopa-sparing options like dopamine agonists. This shift resulted in an increase in behavioral adverse effects, such as impulse control disorders, leading to a subsequent dopamine agonist aversion in the mid-2000s. This review aims to provide a comprehensive evaluation of the existing literature regarding the benefits and drawbacks of levodopa versus levodopa-sparing strategies in drug-naive early-stage Parkinson´s disease.

Assuntos

Assuntos

RESUMO

Purinergic signaling is a crucial determinant in the regulation of pulmonary vascular physiology and presents a promising avenue for addressing lung diseases. This intricate signaling system encompasses two primary receptor classes: P1 and P2 receptors. P1 receptors selectively bind adenosine, while P2 receptors exhibit an affinity for ATP, ADP, UTP, and UDP. Functionally, P1 receptors are associated with vasodilation, while P2 receptors mediate vasoconstriction, particularly in basally relaxed vessels, through modulation of intracellular Ca2+ levels. The P2X subtype receptors facilitate extracellular Ca2+ influx, while the P2Y subtype receptors are linked to endoplasmic reticulum Ca2+ release. Notably, the primary receptor responsible for ATP-induced vasoconstriction is P2X1, with α,ß-meATP and UDP being identified as potent vasoconstrictor agonists. Interestingly, ATP has been shown to induce endothelium-dependent vasodilation in pre-constricted vessels, associated with nitric oxide (NO) release. In the context of P1 receptors, adenosine stimulation of pulmonary vessels has been unequivocally demonstrated to induce vasodilation, with a clear dependency on the A2B receptor, as evidenced in studies involving guinea pigs and rats. Importantly, evidence strongly suggests that this vasodilation occurs independently of endothelium-mediated mechanisms. Furthermore, studies have revealed variations in the expression of purinergic receptors across different vessel sizes, with reports indicating notably higher expression of P2Y1, P2Y2, and P2Y4 receptors in small pulmonary arteries. While the existing evidence in this area is still emerging, it underscores the urgent need for a comprehensive examination of the specific characteristics of purinergic signaling in the regulation of pulmonary vascular tone, particularly focusing on the disparities observed across different intrapulmonary vessel sizes. Consequently, this review aims to meticulously explore the current evidence regarding the role of purinergic signaling in pulmonary vascular tone regulation, with a specific emphasis on the variations observed in intrapulmonary vessel sizes. This endeavor is critical, as purinergic signaling holds substantial promise in the modulation of vascular tone and in the proactive prevention and treatment of pulmonary vascular diseases.

RESUMO

This study assessed the pharmacokinetics and pharmacodynamics of low-dose dexmedetomidine after IV bolus in dogs. Six healthy adult dogs (6.8 ± 3.0 kg) received dexmedetomidine (2 µg.kg-1 IV) over 2 min, using an infusion pump. Blood samples were collected totaling 5 h of monitoring. A validated UHPLC-MS/MS method was used to determine the plasma concentration of dexemedetomidine. For pharmacodynamics, HR, RR, oscillometric MBP, Grint END sedation score were evaluated at baseline (T0), every 3 min (T3 to T21), and after 30 (T30) and 60 (T60) minutes, with p < 0.05. T1/2 was 28.28 ± 6.14 min; the area under the curve was 467.44 ± 60.42 ng/mL/min. The total clearance was 5.46 ± 0.41 mL/min/kg, the Vdss was 146.19 ± 21.04 mL/kg, and the C max was 3.13 ± 1.15 ng/mL. HR (bpm) decreased significantly from T6 (79 ± 21) to T21 (78 ± 31) compared to T0 (116 ± 28). RR(mpm) decreased from T3 (43 ± 44) to T60 (41 ± 23), with T0 being 70 ± 48. The MBP (mmHg) increased at T18 (151 ± 34), T21 (152 ± 35), and T30 (140 ± 27), compared to T0 (111 ± 22). Sedation occurred at all times post-bolus, with a maximum peak at T12 (END 8 ± 6). The low dose of dexmedetomidine provided sedation in all animals, characterizing rapid metabolization and elimination. However, cardiovascular effects still may have negative repercussions in dogs with hemodynamic comorbidities, highlighting the caution and individualization of its use in certain patients.

Assuntos

RESUMO

BACKGROUND: Intravenous infusions of alpha-2 adrenoceptor sedatives and opioids can potentially facilitate surgery in donkeys while standing. Literature on this subject matter is scant. OBJECTIVES: Evaluation of efficacy of sedation from α2-adrenoceptors (dexmedetomidine or xylazine) and butorphanol during ovariectomy in standing donkeys. STUDY DESIGN: Randomised, masked in vivo experiment. METHODS: Thirteen female donkeys were sedated with butorphanol (0.05 mg/kg bwt followed by 0.05 mg/kg bwt/h) IV. Concomitantly, 6 of the 13 jennies were sedated with dexmedetomidine 2.5 mcg/kg bwt followed by 2.5 mcg/kg bwt/h (Dex-B group), while seven jennies were sedated with xylazine 0.5 mg/kg bwt followed by 0.5 mg/kg bwt/h (Xyl-B group). A line block of the left flank and an infiltration block around uterine ligament were performed with lidocaine. While the jennies underwent ovariectomies standing, sedation scores and head height above ground were assessed at 2 and 10 min after sedative boluses and every 10 min thereafter. If sedation was too light or too deep, the dose of dexmedetomidine or xylazine was increased or decreased by 25% of the original infusion rate, while butorphanol infusion rate was constant. Physiological parameters were measured. Normally distributed data were compared using the two-sample t test while repeatedly measured data were tested for differences between and within groups using repeated measures analysis of variance (ANOVA) by ranks followed by a Wilcoxon test with Tukey Honest Significant Difference for multiple testing. Statistical significance was set at p < 0.05. RESULTS: Both Dex-B and Xyl-B caused moderate to marked sedation adequate for ovariectomy in donkeys. Evident sedation was absent by 60 min of termination of infusions. No adverse physiological effects were observed. MAIN LIMITATIONS: Study on ovariectomy cases only, no pharmacokinetic profiling. CONCLUSIONS: Dexmedetomidine or xylazine and butorphanol sedation is feasible for ovariectomy in standing donkeys.

Assuntos

RESUMO

Thyroid cancer has shown a parallel increase with diabetes in the last few years. This narrative review aims to explain the association between these two entities, focusing on insulin resistance as the mediator and exploring the effects of antidiabetic agents on thyroid cancer incidence and progression.We searched Pubmed for English-written articles on insulin resistance, diabetes, antidiabetic treatments, and thyroid cancer reported from January 2019 to April 2023. Exclusion criteria were preclinical and clinical studies involving a population with thyroid dysfunction, benign nodular goiter, or those that only analyzed thyroid cancer's association with obesity.The results of the narrative literature review revealed 96 articles. Additionally, four studies from a manual search were retrieved. After the exclusion criteria were applied, we included 20 studies. Out of 8 studies on insulin-resistant or Metabolic Syndrome patients, all suggest a positive association with thyroid cancer. At the same time, for diabetes, four out of five publications support a link with thyroid cancer. The seven remaining studies on antidiabetics suggest that metformin might benefit thyroid cancer. In contrast, the evidence for an association between Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and increased thyroid cancer findings is limited.In conclusion, the association between thyroid cancer and diabetes may be explained by insulin resistance, as shown in observational studies. However, the causal role is yet to be defined. Although the wide use of different antidiabetic agents has been related to thyroid cancer prevalence and progression, future research with drugs such as metformin or GLP-1 RA is still needed.

Assuntos

RESUMO

Nurr1 is a member of the orphan nuclear receptor family NR4A (nuclear receptor subfamily 4 group A) that modulates inflammation in several cell lineages, both positively and negatively. Macrophages are key regulators of inflammatory responses, yet information about the role of Nurr1 in human macrophages is scarce. Here we examined Nurr1 expression and activity in steady state and activated human macrophages. Pro- and anti-inflammatory macrophages were generated in vitro by culture of blood monocytes with granulocyte/macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF), respectively. Nurr1 expression was predominant in macrophages with the pro-inflammatory phenotype. Nurr1 activation with the agonists 1,1-bis(3'-indolyl)-1-(p-chlorophenyl) methane (C-DIM12) or isoxazolo-pyridinone 7e (IP7e) did not globally modify the polarization status of pro-inflammatory macrophages, but they decreased their production of TNF, IL-1ß, IL-6, IL-8, IL-12 p40, CCL2, IFN-ß, and reactive oxygen species, with variable potencies. Conversely, Nurr1 deficient macrophages increased the expression of transcripts encoding inflammatory mediators, particularly that of IL6, IFNB1, and CCL2. Mechanistically, endogenous Nurr1 interacted with NF-κB p65 in basal conditions and upon lipopolysaccharide (LPS)-mediated activation. C-DIM12 stabilized those complexes in cells exposed to LPS and concurrently decreased NF-κB transcriptional activity and p65 nuclear translocation. Expression of high levels of Nurr1 was associated with a subset of dermal macrophages that display enhanced levels of TNF and lower expression of the anti-inflammatory marker CD163L1 in skin lesions from patients with bullous pemphigoid (BP), a chronic inflammatory autoimmune blistering disorder. These results suggest that Nurr1 expression is linked with the pro-inflammatory phenotype of human macrophages, both in vivo and in vitro, where it may constitute a brake to attenuate the synthesis of inflammatory mediators.

Assuntos

RESUMO

In addition to their well-known classical effects, cannabinoid CB1 and CB2 receptors have also been involvement in both deleterious and protective actions on the heart under various pathological conditions. While the potential therapeutic applications of the endocannabinoid system in the context of cardiovascular function are indeed a viable prospect, significant debate exists within the literature regarding whether CB1, CB2, or a combination of both receptors exert a favorable influence on cardiac function. Hence, the aim of this study was to investigate the effects of CB1 + CB2 or CB2 agonists on cardiac excitation-contraction (E-C) coupling, utilizing fish (Brycon amazonicus) as an experimental model. The CB2 agonist elicited marked positive inotropic and lusitropic responses in isolated ventricular myocardium, induced cyclic adenosine 3',5'-monophosphate (cAMP) production, and upregulated critical Ca2+ handling proteins, such as sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and Na+/Ca2+ exchanger (NCX). Our current study demonstrated, for the first time, that CB2 receptor activation-induced effects improved the efficiency of Ca2+ cycling, excitation-contraction coupling (E-C coupling), and cardiac performance in under physiological conditions. Hence, CB2 receptors could be considered a potential therapeutic target for modulating cardiac contractile dysfunctions.

Assuntos

RESUMO

BACKGROUND: To estimate the contemporary prevalence of established cardiovascular disease (CVD) in adults with type 2 diabetes (T2D) in Mexico. METHODS: CAPTURE was a multinational, non-interventional, cross-sectional study across 13 countries from five continents. Standardized demographic and clinical data were collected from adults with T2D attending a single routine healthcare visit in primary or specialized care between December 2018 and September 2019. Data from Mexico are analyzed in this study. RESULTS: Of the 9,823 patients included in the CAPTURE study, 820 (8.3%) participants were from Mexico, mainly attended in private centers (29.3% in 6 specialized diabetes treatment centers and 70.7% in 26 primary care centers). The median age was 63.0 years, 52.6% were women, the duration of diabetes was 11.8 years and the average HbA1c 7.5%. The weighted prevalence [95% CI] of CVD and atherosclerotic CVD was 36.9% [34.1-39.6] and 29.5% [26.7-32.3], respectively. Additionally, the prevalence of coronary heart disease, heart failure, peripheral arterial disease and cerebrovascular disease was 23.1% [20.6-25-7], 8.4% [6.8-10.0], 5.0% [3.5-6.5] and 3.9% [2.6-5.2], respectively. Glucose lowering drugs were used in 88.5% of patients, being metformin the most commonly drug used (79.4%), followed by sulfonylureas (26.3%). SGLT-2 inhibitors and GLP1 receptor agonists were used in 15.5% and 3.9%, respectively. CONCLUSIONS: In Mexico, nearly four out of ten patients with T2D mainly attended in private centers have CVD, particularly atherosclerotic CVD. Most patients were not taking glucose lowering drugs with proven CV benefit.

RESUMO

Forty-five male non-castrated crossbred Dorper lambs (40.17 ± 0.35 kg body weight, BW) were employed in a completely randomized design with five treatments to investigate the effects of the duration of calcium propionate (CaPr) supplementation (10 g CaPr/lamb/d for 0, 14, 28, or 42 d before slaughter) on lambs finished with zilpaterol hydrochloride (ZH, 7.2 mg/lamb/d for a fixed period of 28 d before slaughter) regarding their productive performance, carcass characteristics, and meat quality. Treatments consisted of the following: (1) No additives (CTL), (2) 0 days on CaPr plus 28 d on ZH, (3) 14 days on CaPr plus 28 d on ZH, (4) 28 days on CaPr plus 28 d on ZH, and (5) 42 days on CaPr plus 28 d on ZH. When compared with CTL, ZH lambs exhibited a similar average daily gain (ADG) but had lower dry matter intake (DMI), leading to increased feed efficiency. Supplementing with ZH alone did not affect carcass traits, visceral mass, whole cuts, or meat quality. Lambs that received both CaPr 28 d and ZH exhibited quadratic increases (p < 0.05) in final body weight (FBW), ADG, and dressing percentage (D%). These increases were optimal at estimated inclusion durations of 26 d for FBW, 30 for ADG, and 39 d for D%. The ADG:DMI ratio and the longissimus muscle area (LMA) both exhibited quadratic increases (p < 0.05). The optimal duration of CaPr supplementation for ADG:DMI ratio was found to be 28 d, while for LMA, it was 14 d. As the period of CaPr supplementation increased, there was a linear increase (p < 0.05) in hot carcass weight, leg circumference, and whole cuts of breast IMPS209 and shoulder IMPS207. Cook loss percent increased quadratically (p < 0.05), and was higher when CaPr was included for an estimated duration of 26 d. As the duration of CaPr supplementation increased, the purge loss percentage (PRL) also increased linearly (p < 0.05). In conclusion, including CaPr in the diet for a duration of 28 d in lambs improved the response to ZH supplementation on the productive performance, carcass weight, and some whole cuts. However, it can also have a negative effect on PRL%.

RESUMO

The aim of this study was to compare the effects of two anesthetic induction protocols for long procedures carried out in the field in Tapiridae. Sixteen tapirs were divided into two groups (n=8) receiving either detomidine (DET) or dexmedetomidine (DEX) for anesthetic induction. All animals were anesthetized by intramuscular administration of a combination of ketamine (1.5 mg/kg), midazolam (0.2 mg/kg), plus either DET (0.04 mg/kg) or DEX (0.007 mg/kg). Anesthetic maintenance was by continuous infusion of ketamine, midazolam, and glyceryl guaiacol ether at 2 mg/kg per hour, 0.1 mg/kg per hour, and 100 mg/kg per hour, respectively). The animals were kept anesthetized for a total of 50 min to allow physical examination and collection of biological material as part of a research program, and physiological variables (heart rate [HR], respiratory rate, oxyhemoglobin saturation [SpO2], rectal temperature [RT], mean arterial pressure [MAP], blood glucose [GLI], and cortisol) and electrocardiogram were recorded during anesthesia. Anesthetic recovery was monitored by two researchers who were not informed of the induction protocol group. The recorded results were statistically evaluated. In both groups there was an initial increase in MAP, which subsequently decreased; RT gradually decreased during anesthesia; HR and GLI increased throughout the procedure; SpO2 was below normal throughout the procedure. Cortisol levels were significantly higher in the DEX group than in the DET group. Also, the animals in the DEX group had a longer recovery time than those in the DET group. On the basis of the results, we conclude that the combination of alpha-2 agonists and midazolam, ketamine, and glyceryl guaicol ether is an appropriate protocol for the anesthesia of tapirs in the field. However, in moderately extended procedures oxygen supplementation is recommended. Additionally, DEX resulted in fewer cardiovascular effects and longer-lasting sedation than DET.

Assuntos

RESUMO

Ocular surface disease (OSD), a disorder affecting the lacrimal and meibomian glands and the corneal and conjunctival epithelium, is a well-known complication of topical glaucoma therapy. OSD can present as a new or pre-existing condition that virtually any anti-glaucoma formulation can exacerbate. As such, both glaucoma and OSD frequently coexist. Typical OSD symptoms include ocular discomfort, redness, burning, and dryness, whereas signs include periorbital and eyelid skin pigmentation, conjunctival scarring, and superficial punctate keratitis. Pressure-lowering eyedrops can cause toxic, allergic, and inflammatory reactions on the ocular surface. The latter can result from either preservatives or direct toxicity from the active molecule. Although usually mild, OSD can cause significant symptoms that lead to poor quality of life, decreased compliance to therapy, glaucoma progression, and worse visual outcomes. Given the chronic nature of glaucoma, lack of curative therapy, and subsequent lifelong treatment, addressing OSD is necessary. This manuscript aims to provide an up-to-date overview of OSD's signs, symptoms, and pathogenic mechanisms from glaucoma therapy toxicity.

RESUMO

The large-conductance Ca2+-activated K+ (BK) channel is widely expressed in the pulmonary blood vessels and plays a significant role in regulating pulmonary vascular tonus. It opens under membrane depolarization, increased intracellular Ca+2 concentration, and chronic hypoxia, resulting in massive K+ efflux, membrane hyperpolarization, decreased L-type Ca+2 channel opening, and smooth muscle relaxation. Several reports have demonstrated an association between BK channel dysfunction and pulmonary hypertension (PH) development. Decreased BK channel subunit expression and impaired regulation by paracrine hormones result in decreased BK channel opening, increased pulmonary vascular resistance, and pulmonary arterial pressure being the cornerstone of PH. The resulting right ventricular pressure overload ultimately leads to ventricular remodeling and failure. Therefore, it is unsurprising that the BK channel has arisen as a potential target for treating PH. Recently, a series of selective, synthetic BK channel agonists have proven effective in attenuating the pathophysiological progression of PH without adverse effects in animal models.

RESUMO

INTRODUCTION: Despite the inherent heterogeneity of the information derived from national registries, they are a useful tool to investigate the epidemiological, clinical, biochemical and treatment outcome characteristics of low prevalence conditions such as acromegaly. Although the information provided by single-center experiences is more homogeneous, these studies usually comprise a limited number of patients and thus, frequently lack statistical power. AREAS COVERED: Registry-based Information regarding the epidemiology, clinical presentation, biochemical and imaging diagnosis, as well as therapeutic outcome and mortality in acromegaly is critically analyzed. EXPERT OPINION: By gathering data from multiple centers in a specific Country, these registries generate important insights into the real-life behavior of this condition, that should be considered, both, in international consensus meetings and in the design of local, Country-specific diagnostic and therapeutic strategies.

Assuntos