Recent studies have revealed a significant relationship between erectile dysfunction (ED) and lower urinary tract symptoms (LUTS), both of which commonly affect middle-aged and older men. These conditions share underlying causes, particularly endothelial dysfunction, atherosclerosis, and chronic pelvic ischemia (CPI). This study investigated the therapeutic potential of LDD175, a large-conductance Ca 2+ -activated K + channel (BKCa channel) opener, in simultaneously treating both conditions using a CPI animal model of male Sprague Dawley rats. Our study investigated the induction of CPI through surgical endothelial damage combined with a high-cholesterol diet. We assessed erectile and voiding functions by measuring intracavernosal pressure (ICP) and intraurethral pressure (IUP), respectively, after nerve stimulation. We performed histological examinations of vascular changes and western blot analyses of cavernous and prostate tissues to understand the underlying mechanisms. This study evaluated the effectiveness of LDD175 compared to standard treatments, such as sildenafil for ED and tamsulosin for LUTS. Therefore, the CPI model successfully demonstrated ED and LUTS symptoms with decreased ICP and increased IUP. Analysis revealed elevated levels of hypoxia-inducible factor-1α, transforming growth factor-β1 and β2 in cavernous tissue, and increased α1A-adrenoceptor expression in prostate tissue. LDD175 administration showed promising results, with dose-dependent improvements in ICP and IUP, and therapeutic effects comparable to those of established treatments. Our findings suggest a novel therapeutic approach that can simultaneously address ED and LUTS, opening new possibilities for clinical application in the treatment of these interconnected conditions.
Male ; Animals ; Erectile Dysfunction/etiology* ; Rats, Sprague-Dawley ; Lower Urinary Tract Symptoms/etiology* ; Ischemia/drug therapy* ; Rats ; Tamsulosin ; Hypoxia-Inducible Factor 1, alpha Subunit/drug effects* ; Sildenafil Citrate/therapeutic use* ; Penis/blood supply* ; Disease Models, Animal ; Transforming Growth Factor beta1/metabolism* ; Pelvis/blood supply* ; Prostate/metabolism* ; Sulfonamides/therapeutic use* ; Large-Conductance Calcium-Activated Potassium Channels/agonists*

Arrhythmia is an external manifestation of cardiac electrophysiological disorder. It exists in healthy people and patients with various heart diseases, which is often associated with other cardiovascular diseases. The contraction and diastole of myocardium are inseparable from the movement of ions. There are many ion channels in the membrane and organelle membrane of myocardium. The dynamic balance of myocardial ions is vital in maintaining myocardial electrical homeostasis. Potassium ion channels that have a complex variety and a wide distribution are involved in the whole process of resting potential and action potential of cardiomyocytes. Potassium ion channels play a vital role in maintaining normal electrophysiological activity of myocardium and is one of the pathogenesis of arrhythmia. Traditional Chinese medicine(TCM)has unique advantages in treating arrhythmia for its complex active components and diverse targets. A large number of TCM preparations have definite effect on treating arrhythmia-related diseases, whose antiarrhythmic mechanism may be related to the effect on potassium channel. This article mainly reviewed the relevant studies on the active components in TCM acting on different potassium channels to provide references for clinical drug use and development.
Humans ; Potassium Channels ; Medicine, Chinese Traditional ; Anti-Arrhythmia Agents/therapeutic use* ; Arrhythmias, Cardiac/drug therapy* ; Heart Diseases/drug therapy* ; Ions

BACKGROUND: Given the general unavailability, common adverse effects, and complicated administration of tetracycline, the clinical application of classic bismuth quadruple therapy (BQT) is greatly limited. Whether minocycline can replace tetracycline for Helicobacter pylori ( H . pylori ) eradication is unknown. We aimed to compare the eradication rate, safety, and compliance between minocycline- and tetracycline-containing BQT as first-line regimens. METHODS: This randomized controlled trial was conducted on 434 naïve patients with H . pylori infection. The participants were randomly assigned to 14-day minocycline-containing BQT group (bismuth potassium citrate 110 mg q.i.d., esomeprazole 20 mg b.i.d., metronidazole 400 mg q.i.d., and minocycline 100 mg b.i.d.) and tetracycline-containing BQT group (bismuth potassium citrate/esomeprazole/metronidazole with doses same as above and tetracycline 500 mg q.i.d.). Safety and compliance were assessed within 3 days after eradication. Urea breath test was performed at 4-8 weeks after eradication to evaluate outcome. We used a noninferiority test to compare the eradication rates of the two groups. The intergroup differences were evaluated using Pearson chi-squared or Fisher's exact test for categorical variables and Student's t -test for continuous variables. RESULTS: As for the eradication rates of minocycline- and tetracycline-containing BQT, the results of both intention-to-treat (ITT) and per-protocol (PP) analyses showed that the difference rate of lower limit of 95% confidence interval (CI) was >-10.0% (ITT analysis: 181/217 [83.4%] vs . 180/217 [82.9%], with a rate difference of 0.5% [-6.9% to 7.9%]; PP analysis: 177/193 [91.7%] vs . 176/191 [92.1%], with a rate difference of -0.4% [-5.6% to 6.4%]). Except for dizziness more common (35/215 [16.3%] vs . 13/214 [6.1%], P = 0.001) in minocycline-containing therapy groups, the incidences of adverse events (75/215 [34.9%] vs . 88/214 [41.1%]) and compliance (195/215 [90.7%] vs . 192/214 [89.7%]) were similar between the two groups. CONCLUSION: The eradication efficacy of minocycline-containing BQT was noninferior to tetracycline-containing BQT as first-line regimen for H . pylori eradication with similar safety and compliance. TRIAL REGISTRATION ClinicalTrials.gov, ChiCTR 1900023646.
Humans ; Bismuth/therapeutic use* ; Metronidazole/therapeutic use* ; Esomeprazole/pharmacology* ; Minocycline/pharmacology* ; Helicobacter pylori ; Potassium Citrate/therapeutic use* ; Anti-Bacterial Agents ; Tetracycline/adverse effects* ; Helicobacter Infections/drug therapy* ; Drug Therapy, Combination ; Amoxicillin

Hyperkalemia was one of the complications after primary aldosteronism surgery. Hyperkalemia after primary aldosteronism surgery was uncommon in clinical practice, especially persistent and serious hyperkalemia was rare. This complication was not attached great importance in clinical work. A case about persistent and serious hyperkalemia after primary aldosteronism adrenal adenoma surgery was reported and the patient was followed-up for fourteen months in this study. This patient had a laparoscopic adrenalectomy due to primary aldosteronism. Hyperkalemia was detected one month after surgery of this patient, the highest level of plasma potassium was 7.0 mmol/L. The patient felt skin itchy, nausea, palpitation. Plasma aldosterone concentration fell to 2.12 ng/dL post-operation from 35.69 ng/dL pre-operation, zona glomerulosa insufficiency was confirmed by hormonal tests in this patient after surgery. And levels of 24 hours urinary potassium excretion declined. Decrease of aldosterone levels after surgery might be the cause of hyperkalemia. Hyperkalemia lasted for 14 months after surgery and kalemia-lowering drugs were needed. A systemic search with "primary aldosteronism", "hyperkalemia", "surgical treatment" was performed in PubMed and Wanfang Database for articles published between January 2009 and December 2019. Literature review indicated that the incidence of hyperkalemia after primary aldosteronism surgery was 6% to 29%. Most of them was mild to moderator hyperkalemia (plasma potassium 5.5 to 6.0 mmol/L) and transient. 19% to 33% in hyperkalemia patients was persistent hyperkalemia. Previous studies in the levels of plasma potassium reached the level as high as 7 mmol/L in our case were rare. Whether hypoaldosteronemia was the cause of hyperkalemia was not consistent in the published studies. Risk factors of hyperkalemia after primary aldosteronism surgery included kidney dysfunction, old age, long duration of hypertention. This paper aimed to improve doctors' aweareness of hyperkalemia complication after primary aldosteronism surgery. Plasma potassium should be monitored closely after primary aldosteronism surgery, especially in the patients with risk factors. Some patients could have persistent and serious hyperkalemia, and need medicine treatment.
Adrenalectomy/adverse effects* ; Aldosterone/therapeutic use* ; Humans ; Hyperaldosteronism/surgery* ; Hyperkalemia/surgery* ; Potassium/therapeutic use*

BACKGROUND: Histidine-tryptophan-ketoglutarate (HTK) is a solution commonly used for organ transplantation. However, there is no certified fixed regimen for on-pump heart surgery in neonates. We aimed to retrospectively evaluate the outcomes related to different HTK dosages and to analyze the safety of high-dosage perfusion. METHODS: A total of 146 neonates who underwent on-pump heart surgery with single-shot HTK perfusion were divided into two groups according to HTK dosages: a standard-dose (SD) group (n = 63, 40 mL/kg < HTK ≤ 60 mL/kg) and a high-dose (HD) group (n = 83, HTK >60 mL/kg). Propensity score matching (PSM) was performed to control confounding bias. RESULTS: The SD group had a higher weight (3.7 ± 0.4 vs. 3.4 ± 0.4 kg, P < 0.0001), a lower proportion of complete transposition of the great artery (69.8% vs. 85.5%, P = 0.022), a lower cardiopulmonary bypass (CPB) time (123.5 [108.0, 136.0] vs. 132.5 [114.8, 152.5] min, P = 0.034), and a lower aortic x-clamp time (82.9 ± 27.1 vs. 95.5 ± 26.0 min, P = 0.005). After PSM, 44 patients were assigned to each group; baseline characteristics and CPB parameters between the two groups were comparable. There were no significant differences in peri-CPB blood product consumption after PSM (P > 0.05). The incidences of post-operative complications were not significantly different between the two groups. There were no significant differences in ventilation time, intensive care unit stay, and post-operative hospital stay (P > 0.05). Follow-up echocardiography outcomes at 1 month, 3 to 6 months, and 1 year showed that left ventricular ejection fraction and end-diastolic dimension were comparable between the two groups. CONCLUSIONS In neonatal on-pump cardiac surgery patients, single-shot HD (>60 mL/kg) HTK perfusion had a comparable heart protection effect and short-term post-operative prognosis as standard dosage perfusion of 40 to 60 mL/kg. Thus, this study provides supporting evidence of the safety of HD HTK perfusion.
Glucose/therapeutic use* ; Histidine ; Humans ; Infant, Newborn ; Mannitol ; Organ Preservation Solutions ; Potassium Chloride/therapeutic use* ; Prognosis ; Retrospective Studies ; Stroke Volume ; Tryptophan ; Ventricular Function, Left

General anesthesia is an unconscious state induced by anesthetics for surgery. The molecular targets and cellular mechanisms of general anesthetics in the mammalian nervous system have been investigated during past decades. In recent years, K channels have been identified as important targets of both volatile and intravenous anesthetics. This review covers achievements that have been made both on the regulatory effect of general anesthetics on the activity of K channels and their underlying mechanisms. Advances in research on the modulation of K channels by general anesthetics are summarized and categorized according to four large K channel families based on their amino-acid sequence homology. In addition, research achievements on the roles of K channels in general anesthesia in vivo, especially with regard to studies using mice with K channel knockout, are particularly emphasized.
Anesthetics, General ; pharmacology ; therapeutic use ; Animals ; Humans ; Potassium Channels ; metabolism

Actinomycosis ; complications ; drug therapy ; pathology ; Aged, 80 and over ; Amoxicillin-Potassium Clavulanate Combination ; therapeutic use ; Anti-Bacterial Agents ; therapeutic use ; Cephalexin ; therapeutic use ; Ciprofloxacin ; therapeutic use ; Clindamycin ; therapeutic use ; Coinfection ; drug therapy ; Drug Resistance, Bacterial ; Escherichia coli Infections ; complications ; drug therapy ; Humans ; Male ; Pseudomonas Infections ; complications ; drug therapy ; Skin Diseases, Bacterial ; complications ; drug therapy ; pathology ; Staphylococcal Skin Infections ; complications ; drug therapy ; Thigh ; Trimethoprim, Sulfamethoxazole Drug Combination ; therapeutic use

OBJECTIVETo assess the biological effects of the six-herb mixture Anti-Insomia Formula (AIF) extract using caffeine-induced insomnia Drosophila model and short-sleep mutants.

METHODSCaffeineinduced insomnia wild-type Drosophila and short-sleep mutant flies minisleep (mns) and Hyperkinetic(Y) (Hk(Y)) were used to assess the hypnotic effects of the AIF in vivo. The night time activity, the amount of night time sleep and the number of sleep bouts were determined using Drosophila activity monitoring system. Sleep was defined as any period of uninterrupted behavioral immobility (0 count per minute) lasting > 5 min. Night time sleep was calculated by summing up the sleep time in the dark period. Number of sleep bouts was calculated by counting the number of sleep episodes in the dark period.

RESULTSAIF at the dosage of 50 mg/mL, effectively attenuated caffeine-induced wakefulness (P<0.01) in wild-type Canton-S flies as indicated by the reduction of the sleep bouts, night time activities and increase of the amount of night time sleep. AIF also significantly reduced sleeping time of short-sleep Hk(Y) mutant flies (P<0.01). However, AIF did not produce similar effect in mns mutants.

CONCLUSIONAIF might be able to rescue the abnormal condition caused by mutated modulatory subunit of the tetrameric potassium channel, but not rescuing the abnormal nerve firing caused by Shaker gene mutation. This study provides the scientific evidence to support the use of AIF in Chinese medicine for promoting sleep quality in insomnia.

Animals ; Caffeine ; Chromatography, High Pressure Liquid ; Disease Models, Animal ; Drosophila melanogaster ; drug effects ; physiology ; Hypnotics and Sedatives ; pharmacology ; therapeutic use ; Mutation ; genetics ; Potassium Channels ; genetics ; Sleep ; drug effects ; Sleep Initiation and Maintenance Disorders ; drug therapy ; Wakefulness ; drug effects

Traumatic gas gangrene is a fatal infection mainly caused by Clostridium perfringens. It is a challenge to manage gas gangrene in open wounds and control infection after debridement or amputation. The aim of the present study was to use vacuum sealing drainage (VSD) with continuous irrigation of potassium permanganate to manage infective wounds of gas gangrene and observe its clinical efficacy. A total of 48 patients with open traumatic gas gangrene infection were included in this study. Amputations were done for 27 patients, and limb salvage procedures were performed for the others. After amputation or aggressive debridement, the VSD system, including polyvinyl alcohol (PVA) foam dressing and polyurethane (PU) film, with continuous irrigation of 1:5000 potassium permanganate solutions, was applied to the wounds. During the follow-up, all the patients healed without recurrence within 8-18 months. There were four complications. Cardiac arrest during amputation surgery occurred in one patient who suffered from severe septic shock. Emergent resuscitation was performed and the patient returned to stable condition. One patient suffered from mixed infection of Staphylococcal aureus, and a second-stage debridement was performed. One patient suffered from severe pain of the limb after the debridement. Exploratory operation was done and the possible reason was trauma of a local peripheral nerve. Three cases of crush syndrome had dialysis treatment for concomitant renal failure. In conclusion, VSD can convert open wound to closed wound, and evacuate necrotic tissues. Furthermore, potassium permanganate solutions help eliminate anaerobic microenvironment and achieve good therapeutic effect on gas gangrene and mixed infection. VSD with continuous irrigation of potassium permanganate is a novel, simple and feasible alternative for severe traumatic open wounds with gas gangrene infection.
Adolescent ; Adult ; Aged ; Child ; Drainage ; Female ; Gas Gangrene ; etiology ; therapy ; Humans ; Male ; Middle Aged ; Negative-Pressure Wound Therapy ; methods ; Potassium Permanganate ; therapeutic use ; Retrospective Studies ; Therapeutic Irrigation ; Treatment Outcome ; Young Adult

BACKGROUNDOuabain and digoxin are important cardiac glycoside and related to many cardiovascular diseases. The purpose of this study was to investigate the changes of sodium pump α-subunit expression in rats and compare the effects of ouabain (OUA) and digoxin (DIG) on the development of hypertension.

METHODSIn situ hybridization was performed. Specific sequence oligonucleotide probe tailing with a Dig-dUTP hybrid to target nucleic acids of the sodium pump α-subunit. According to counting positive particles sodium pump subunit expression was analyzed with statistical methods.

RESULTSOn day 16 of drug administration, the blood pressure of rats increased significantly in the OUA group. In the DIG group, the blood pressure revealed no significant difference when compared to the control group. In addition, the effects of OUA and DIG on sodium pump α-subunit RNA expression in tissues differed.

CONCLUSIONSOUA and DIG can not only change the configuration of the sodium pump to depress their activity, but also influence their gene expression which is important in the mechanism of hypertension. This may be a key point in the pathogenesis of hypertension in the manner in which OUA differs from DIG and changes the sodium pump gene expression in the arteries and kidneys of rats.

Animals ; Blood Pressure ; drug effects ; Digoxin ; therapeutic use ; Hypertension ; drug therapy ; In Situ Hybridization ; Male ; Ouabain ; therapeutic use ; Rats, Sprague-Dawley ; Sodium-Potassium-Exchanging ATPase ; metabolism