Search Results (31)

This study aims to apply standard statistics and InterCriteria analysis (ICrA) for assessing the effects of different transcranial magnetic stimulation (TMS) intensities and three muscle conditions on the evoked responses of the first dorsal interosseous muscle (FDIM). Surface electromyograms from the right FDIM of ten right-handed healthy volunteers were recorded, and amplitudes of motor evoked potentials (MEPs), latencies of MEPs, and silent periods were obtained. ICrA was used for the first time as a supplementary tool along with the applied statistical methods. Three case studies were processed by the ICrA approach for a wide examination of neuromuscular excitability in humans. As a result, the relations between increasing TMS intensities, MEP amplitudes, MEP latencies, and silent periods were established at relaxed muscle condition, isometric index finger abduction condition, and co-contraction of antagonist muscles condition. Also, the dependencies between MEP amplitudes, MEP latencies, and silent periods themselves, and for different TMS intensities, were outlined. The results confirmed relations known from the literature and showed new ones. Full article

Background/Objectives: Mebeverine hydrochloride (MBH) is an antispasmodic agent used to regulate bowel movements and relax intestinal smooth muscle, but its application is limited by specific side effects; therefore, this study investigates the effects of previously synthesized MBH-loaded silver nanoparticles (AgNPs) on smooth muscle contractile activity and their anti-inflammatory potential as an alternative delivery system. Methods: The interactions of AgNPs with cholinergic inhibitors, selective antagonists, Ca²⁺ blockers, and key neurotransmitters were analyzed. In vitro, albumin denaturation suppression and ex vivo assays evaluated the anti-inflammatory effects of AgNPs-MBH, validated using a DFT in silico approach. To comprehensively assess the systemic impact and IBS treatment potential of AgNPs-MBH, we also examined in vitro their antimicrobial activity and hepatic cell responses, as the liver is a key organ in evaluating the overall safety and efficacy of nanoparticles. Additionally, the drug-release capabilities of Ag NPs were established. Results: Our findings indicate that AgNPs with MBH do not affect blocked cholinergic receptors, but their effects are more pronounced and distinct in amplitude and character than MBH. MBH-loaded AgNPs showed a lower anti-inflammatory effect than MBH but were still better than diclofenac. They also affected hepatic cell morphology and proliferation, suggesting potential for enhanced therapeutic efficacy. Drug-loaded AgNPs are considered not bactericidal. Conclusions: Based on our results, drug-loaded AgNPs might be a promising medication delivery system for MBH and a useful treatment option for IBS. Future in vivo and preclinical experiments will contribute to the establishment of drug-loaded AgNPs in IBS treatment. Full article

The present study investigated the acute effects of different stretching modalities applied within a warm-up on flexibility and vertical jump height. Thirty-seven young adults participated in four randomized experimental sessions, each corresponding to a different condition: static stretch (SS), dynamic stretch (DS), contract–relax with antagonist contraction (CRAC) or a control condition with no stretch (CTRL). Conditions were five min in total duration, including 2 × 15 s stretches for each muscle group (knee flexor, knee extensor, and plantar flexor muscles). Ten min and five min of cycling preceded and followed these procedures, respectively. Hamstring flexibility and a series of countermovement jump (CMJ) measurements were interspersed within this procedure. Except for CTRL, hamstring flexibility significantly increased (p < 0.01) after all experimental procedures (7.5 ± 6.6%, 4.1 ± 4.9%, and 2.7 ± 6.0% for CRA, SS, and DS, respectively). The relative increase was significantly greater for CRAC as compared CTRL (p < 0.001). Vertical jump height significantly decreased (p < 0.05) immediately after SS (−2.3 ± 3.9%), CTRL (−2.3 ± 3.5%), and CRAC (−3.2 ± 3.3%). Jump height was unchanged after DS (0.4 ± 4.5%). Whatever the condition, no additional jump height alteration was obtained after the re-warm-up. The main findings of the present study revealed that DS is more appropriate for maintaining vertical jump height. However, stretching has no major effect when performed within a warm-up. In contrast, if the main objective is to increase flexibility, CRAC is recommended. Full article

Background/Objectives: No study has simulated rocuronium (Rb) effect-site concentrations (Ce_Rb) using real-time data—such as Rb concentrations, train-of-four (TOF) count (TOFC), and TOF ratio (TOFR)—under mechanical Rb administration. Therefore, we aimed to investigate post-operative recurarization and changes in the Ce_Rb after sugammadex (SGX) administration under conditions where Rb dosing was strictly administered using an automated delivery system for total intravenous anesthesia. Methods: This non-interventional, retrospective, observational study included 74 patients from an existing clinical trial who met the study criteria. Rb was automatically administered during surgery to maintain a TOFC of 1. SGX (2 mg/kg) was manually administered post-surgery, and the time until the TOFR reached ≥0.9 (if the time exceeded 3 min, 0.5 mg/kg SGX was added every minute). The results were analyzed using a pharmacokinetic (PK)–pharmacodynamic (PD) simulation model of the Rb-SGX complex. Results: The average total dose of administered SGX was 2.2 ± 0.4 mg/kg (mean ± standard deviation). The time from SGX administration till the TOFR reached ≥0.9 was 2.9 ± 1.1 min. Furthermore, Ce_Rb at recovery (Ce_r) was 0.3 ± 0.2 μg/mL. Notably, no cases showed post-operative recurarization within 24 h of surgery. PK–PD model simulations revealed that Ce_Rb increased again after reaching the lowest Ce_Rb in 72 cases, although no increase was recorded beyond Ce_r, suggesting no numerical risk of recurarization. Conclusions: Our results show that if TOFC of 1 is strictly maintained intraoperatively and SGX is administered till the TOFR reaches ≥0.9, post-operative recurarization does not occur. Full article

The amphibian skin secretions are excellent sources of bioactive peptides, some of which and their derivatives exhibit multiple properties, including antibacterial and antagonism against bradykinin. A novel peptide Senegalin-2 was isolated from the skin secretions of Kassina senegalensis frog. Senegalin-2 relaxed rat bladder smooth muscle (EC₅₀ 17.94 nM) and ileum smooth muscle (EC₅₀ 135 nM), inhibited S. aureus and MRSA at 2 μM, and exhibited low hemolytic activity with no cytotoxicity. To design effective bradykinin antagonists, Senegalin-2 was conjugated with bradykinin to synthesize Senegalin-2BK. This modification retained potent activity against Gram-positive bacteria. Compared to Senegalin-2, Senegalin-2BK significantly reduced hemolysis and exhibited a more than threefold increase in the selectivity index. Furthermore, Senegalin-2BK contracted the bladder (EC₅₀ 2.83 μM) and ileum (EC₅₀ 56.64 nM)’s smooth muscle. The pretreatment with 10⁻⁷ M Senegalin-2BK reduced the 10⁻⁶ M bradykinin contraction on the bladder by over 70%. In conclusion, Senegalin-2 has dual functionalities as an antibacterial agent and muscle relaxant, positioning it as a potential therapeutic candidate for managing overactive bladder. As a synthetically derived bradykinin antagonist and myotropic peptide with antibacterial properties, Senegalin-2BK shows promise in effective therapies for relieving pain, inflammation, and addressing muscular disorders such as urinary retention, constipation, and infections. Full article

Cardiovascular complications are the major cause of diabetes mellitus-related morbidity and mortality. Increased renin–angiotensin–aldosterone system activity and decreased β-adrenergic receptor (β-AR) responsiveness contribute to diabetic cardiac dysfunction. We evaluated the effect of sacubitril/valsartan (neprilysin inhibitor plus angiotensin receptor antagonist combination) and valsartan treatments on the diabetic cardiac function through β-AR responsiveness and on protein expression of diastolic components. Six-week-old male Sprague Dawley rats were divided into control, diabetic, sacubitril/valsartan (68 mg/kg)-, and valsartan-treated (31 mg/kg) diabetic groups. Diabetes was induced by a high-fat diet plus low-dose streptozotocin (30 mg/kg, intraperitoneal). After 10 weeks of diabetes, rats were treated for 4 weeks. Systolic/diastolic function was assessed by in vivo echocardiography and pressure–volume loop analysis. β-AR-mediated responsiveness was assessed by in vitro papillary muscle and Langendorff heart experiments. Protein expression of sarcoplasmic reticulum calcium ATPase2a, phospholamban, and phosphorylated phospholamban was determined by Western blot. Sacubitril/valsartan improved ejection fraction and fractional shortening to a similar extent as valsartan alone. None of the treatments affected in vivo diastolic parameters or the expression of related proteins. β₁-/β₂-AR-mediated responsiveness was partially restored in treated animals. β₃-AR-mediated cardiac relaxation (an indicator of diastolic function) responses were comparable among groups. The beneficial effect of sacubitril/valsartan on systolic function may be attributed to improved β₁-/β₂-AR responsiveness. Full article

Leonurus japonicus Houtt is an exceptional medicinal herb used to treat obstetrical and gynecological diseases in traditional Chinese medicine, and it has significant effects on the treatment of dysmenorrhea and postpartum hemorrhage. This study investigated the effects of coumarins with diverse substituent groups from L. japonicus on isolated uterine smooth muscle and the preliminary mechanism of the most effective compound. Eight coumarins isolated from L. japonicus were assessed for their effects on the isolated uterine smooth muscle of nonpregnant rats in vitro. Coumarins 1 and 2 significantly promoted the contraction of rat uterine smooth muscle strips, whereas coumarins 3–5 showed remarkable relaxing effects against oxytocin (OT)-induced rat uterine smooth muscle contraction. Further mechanism investigations revealed that bergapten (coumarin 1) significantly increased the level of Ca²⁺ in uterine tissues by promoting extracellular Ca²⁺ influx and intracellular Ca²⁺ release, which were related to the activation of L-type Ca²⁺ channels and α-receptors. By contrast, osthole (coumarin 5), an α receptor antagonist, inhibited OT-induced uterine smooth muscle contraction by decreasing the level of Ca²⁺ in uterine tissues via inhibition of extracellular Ca²⁺ influx and intracellular Ca²⁺ release. This study demonstrates that the coumarins from L. japonicus are effective substances for regulating uterine smooth muscle contraction, but different coumarins with diverse substituent groups have different, even opposite effects. It can be inferred that coumarins are closely related to the efficacy of L. japonicus in the treatment of dysmenorrhea and postpartum hemorrhage. Full article

The Cupressaceae family includes species considered to be medicinal. Their essential oil is used for headaches, colds, cough, and bronchitis. Cedar trees like Chamaecyparis lawsoniana (C. lawsoniana) are commonly found in urban areas. We investigated whether C. lawsoniana exerts some of its effects by modifying airway smooth muscle (ASM) contractility. The leaves of C. lawsoniana (363 g) were pulverized mechanically, and extracts were obtained by successive maceration 1:10 (w:w) with methanol/CHCl₃. Guinea pig tracheal rings were contracted with KCl, tetraethylammonium (TEA), histamine (HIS), or carbachol (Cch) in organ baths. In the Cch experiments, tissues were pre-incubated with D-600, an antagonist of L-type voltage-dependent Ca²⁺ channels (L-VDCC) before the addition of C. lawsoniana. Interestingly, at different concentrations, C. lawsoniana diminished the tracheal contractions induced by KCl, TEA, HIS, and Cch. In ASM cells, C. lawsoniana significantly diminished L-type Ca²⁺ currents. ASM cells stimulated with Cch produced a transient Ca²⁺ peak followed by a sustained plateau maintained by L-VDCC and store-operated Ca²⁺ channels (SOCC). C. lawsoniana almost abolished this last response. These results show that C. lawsoniana, and its active metabolite quercetin, relax the ASM by inhibiting the L-VDCC and SOCC; further studies must be performed to obtain the complete set of metabolites of the extract and study at length their pharmacological properties. Full article

Numerous studies suggest the involvement of adenosine-5′-triphosphate (ATP) and similar nucleotides in the pathophysiology of asthma. Androgens, such as testosterone (TES), are proposed to alleviate asthma symptoms in young men. ATP and uridine-5′-triphosphate (UTP) relax the airway smooth muscle (ASM) via purinergic P2Y₂ and P2Y₄ receptors and K⁺ channel opening. We previously demonstrated that TES increased the expression of voltage-dependent K⁺ (K_V) channels in ASM. This study investigates how TES may potentiate ASM relaxation induced by ATP and UTP. Tracheal tissues treated with or without TES (control group) from young male guinea pigs were used. In organ baths, tracheas exposed to TES (40 nM for 48 h) showed enhanced ATP- and UTP-evoked relaxation. Tetraethylammonium, a K⁺ channel blocker, annulled this effect. Patch-clamp experiments in tracheal myocytes showed that TES also increased ATP- and UTP-induced K⁺ currents, and this effect was abolished with flutamide (an androgen receptor antagonist). K_V channels were involved in this phenomenon, which was demonstrated by inhibition with 4-aminopyridine. RB2 (an antagonist of almost all P2Y receptors except for P2Y₂), as well as N-ethylmaleimide and SQ 22,536 (inhibitors of G proteins and adenylyl cyclase, respectively), attenuated the enhancement of the K⁺ currents induced by TES. Immunofluorescence and immunohistochemistry studies revealed that TES did not modify the expression of P2Y₄ receptors or COX-1 and COX-2, while we have demonstrated that this androgen augmented the expression of K_V1.2 and K_V1.5 channels in ASM. Thus, TES leads to the upregulation of P2Y₄ signaling and K_V channels in guinea pig ASM, enhancing ATP and UTP relaxation responses, which likely limits the severity of bronchospasm in young males. Full article

Coccoloba uvifera is a Mayan medicinal plant, and these leaves are used as antidiarrheal and diuretic agents. In the present work, we develop in-vitro, ex-vivo, in-vivo, and in-silico strategies to evaluate several aqueous extracts of C. uvifera leaves. In vitro tests showed that decoction extract (CuDe) presented the best yield and chlorophyll, phenol, and flavonoid content; however, CuDe showed low antioxidant activity (DPPH model). All aqueous extracts exert spasmolytic and vasorelaxant activity in a concentration-dependent manner (ex vivo), and in vivo tests showed that CuDe exerts the best antiperistaltic and diuretic effects. The in-silico analysis suggests that C. uvifera triterpenes act as a ligand of GPCR, and β-sitosterol could act as an antagonist of muscarinic acetylcholine receptor subtype 3 (m3AChR). In the context of aqueous extracts of C. uvifera, β-sitosterol and their heterosides were identified by FTIR and ¹H-NMR spectroscopy. The concerted binding of β-sitosterol and other triterpenes within the m3AChR binding site may be relevant for the induction of relaxant effects at the gastrointestinal smooth muscle level. In this context, C. uvifera is a high-value plant species that requires analytical and pharmacological studies to confirm traditional medicinal use. Full article

The tunica muscularis of mammalian esophagi is composed of striated muscle and smooth muscle. Contraction of the esophageal striated muscle portion is mainly controlled by cholinergic neurons. On the other hand, smooth muscle contraction and relaxation are controlled not only by cholinergic components but also by non-cholinergic components in the esophagus. Adenosine triphosphate (ATP) is known to regulate smooth muscle contraction and relaxation in the gastrointestinal tract via purinergic receptors. However, the precise mechanism of purinergic regulation in the esophagus is still unclear. Therefore, the aim of the present study was to clarify the effects of ATP on the mechanical responses of the esophageal muscle in mice. An isolated segment of the mouse esophagus was placed in a Magnus’s tube and longitudinal mechanical responses were recorded. Exogenous application of ATP induced contractile responses in the esophageal preparations. Tetrodotoxin, a blocker of voltage-dependent sodium channels in neurons and striated muscle, did not affect the ATP-induced contraction. The ATP-evoked contraction was blocked by pretreatment with suramin, a purinergic receptor antagonist. RT-PCR revealed the expression of mRNA of purinergic receptor genes in the mouse esophageal tissue. The findings suggest that purinergic signaling might regulate the motor activity of mouse esophageal smooth muscle. Full article

A recent in vivo study in pigs demonstrated the hypotensive properties of essential oil extracted from the blossoming plant Elsholtzia ciliata. This study was designed to examine the effect of E. ciliata essential oil (EO) on smooth muscle contraction. Tension measurements were performed on prostate strips and intact aortic rings isolated from rats. Results showed that EO caused a concentration-dependent reduction in phenylephrine-induced contraction of both the prostate and aorta, with a more pronounced inhibitory effect in the prostate. The IC₅₀ of EO for the prostate was 0.24 ± 0.03 µL/mL (n = 10) and for the aorta was 0.72 ± 0.11 µL/mL (n = 4, p < 0.05 vs. prostate). The chromatographic analysis identified elsholtzia ketone (10.64%) and dehydroelsholtzia ketone (86.23%) as the predominant compounds in the tested EO. Since both compounds feature a furan ring within their molecular structure, other furan ring-containing compounds, 2-acetylfuran (2AF) and 5-methylfurfural (5MFF), were examined. For the first time, our study demonstrated the relaxant effects of 2AF and 5MFF on smooth muscles. Further, results showed that EO, 2AF, and 5MFF altered the responsiveness of prostate smooth muscle cells to phenylephrine. Under control conditions, the EC50 of phenylephrine was 0.18 ± 0.03 µM (n = 5), while in the presence of EO, 2AF, or 5MFF, the EC50 values were 0.81 ± 0.3 µM (n = 5), 0.89 ± 0.11 µM (n = 5), and 0.69 ± 0.23 µM (n = 4), respectively, p < 0.05 vs. control. Analysis of the affinity of EO for α₁-adrenergic receptors in the prostate suggested that EO at a certain range of concentrations has a competitive antagonistic effect on α₁-adrenergic receptors. In conclusion, EO elicits a relaxant effect on smooth muscles which may be related to the inhibition of α₁-adrenoreceptors. Full article

Chiari Malformation Type I (CM) includes a range of cranial abnormalities at the junction of the skull with the spine, with common symptoms including pain and headaches. Currently, CM pain is managed medically through anti-inflammatory drugs, muscle relaxants, and opioids, while surgical management includes posterior fossa decompression. Given the adverse effects of opioid use, and an ongoing opioid epidemic, there is a need for safe, non-opioid alternatives for clinical pain management. This systematic review was performed to provide an update on the current literature pertaining to the treatment of CM pain with non-opioid alternatives. A literature search was performed in June 2022 utilizing the PubMed and Google Scholar databases, and articles were identified that included information regarding non-opioid pain management in CM patients. A total of 90 articles were obtained from this search, including 10 relevant, drug-specific studies. Two independent reviewers selected and included all relevant articles based on the chosen search criteria to minimize bias risk. Currently available treatments for neurosurgical pain management include anticonvulsants, corticosteroids, NSAIDs, anti-inflammatory drugs, NMDA receptor antagonists, local anesthetics, nerve blocks, scalp blocks, and neuromuscular blocks. While more information is needed on the use of non-opioid pain management, the present literature provides potential evidence of its efficacy amongst the CM patient population, on account of the success that non-opioid pain management has demonstrated within other neurological pain syndromes. Further research into non-pharmacological pain management would also benefit the CM population and could be generalized to related conditions. Full article

The present study aimed to investigate the acute effects and the mechanism of ketamine on nicotine-induced relaxation of the corpus cavernosum (CC) in mice. This study measured the intra-cavernosal pressure (ICP) of male C57BL/6 mice and the CC muscle activities using an organ bath wire myograph. Various drugs were used to investigate the mechanism of ketamine on nicotine-induced relaxation. Direct ketamine injection into the major pelvic ganglion (MPG) inhibited MPG-induced increases in ICP. D-serine/L-glutamate-induced relaxation of the CC was inhibited by MK-801 (N-methyl-D-aspartate (NMDA) receptor inhibitor), and nicotine-induced relaxation was enhanced by D-serine/L-glutamate. NMDA had no effect on CC relaxation. Nicotine-induced relaxation of the CC was suppressed by mecamylamine (a non-selective nicotinic acetylcholine receptor antagonist), lidocaine, guanethidine (an adrenergic neuronal blocker), N^w-nitro-L-arginine (a non-selective nitric oxide synthase inhibitor), MK-801, and ketamine. This relaxation was almost completely inhibited in CC strips pretreated with 6-hydroxydopamine (a neurotoxic synthetic organic compound). Ketamine inhibited cavernosal nerve neurotransmission via direct action on the ganglion and impaired nicotine-induced CC relaxation. The relaxation of the CC was dependent on the interaction of the sympathetic and parasympathetic nerves, which may be mediated by the NMDA receptor. Full article

Cinnamon is one of the most commonly used spices worldwide. In some Arab countries, cinnamon is used with other ingredients to relieve bronchospasm and treatment of airways-related disorders. In the current study, GC, GC-MS and tracheal relaxant effect comparison were performed using the three available types in Saudi Arabia, Cinnamomum verum (Ceylon cinnamon), C. cassia (Chinese cinnamon) and C. loureiroi (Vietnamese cinnamon). The essential oil of C. verum was the most potent in the relaxation of guinea pig isolated tracheal muscles against carbachol (CCh, 1 uM)-evoked bronchospasm at the concentration range from 0.03 to 3 mg/mL followed by C. bureiroi at 0.03 to 5 mg/mL; whereas, C. cassia was the least potent oil. Cinnamaldehyde (1), isolated as the main component of the three oils induced complete relaxation of low K⁺ (25 mM)-evoked contractions, with mild effect on the contractions evoked by high K⁺ (80 mM). Pre-incubation of the tracheal tissues with glibenclamide (10 μM) significantly opposed the relaxation of low K⁺ by cinnamaldehyde. The standard drug, cromakalim also inserted glibenclamide-sensitive inhibition of low K⁺ without relaxing high K⁺. These results indicate that cinnamaldehyde acts predominantly by ATP-specific K⁺ channel opening followed by weak Ca⁺⁺ antagonistic effects. The obtained results justify the medicinal value of cinnamon oil in respiratory disorders. Full article