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Relaxant Effects of Piperine and Piperlongumine from Piper longum Fruits on Porcine Coronary Artery.Biological & Pharmaceutical Bulletin Jan 2024Since ancient times, Piper longum Linn. fruits have been recognized for exhibiting various effects, including the diaphoretic effects linked to enhanced blood flow....
Since ancient times, Piper longum Linn. fruits have been recognized for exhibiting various effects, including the diaphoretic effects linked to enhanced blood flow. Piperine and piperlongumine coexist in Piper longum Linn. fruits, although the cardiovascular effects of both compounds remain elusive. We investigated their action of piperine and piperlongumine in porcine coronary arteries, comparing them to the Ca channel antagonist diltiazem. Piperlongumine, unlike piperine or diltiazem, concentration-dependently inhibited basal contractile tone in endothelium-denuded coronary arteries. All three compounds inhibit tonic contractions induced by high potassium chloride (KCl) concentrations. The order of relaxation potency indexed by the half-maximal effective concentration (EC) were as follows: diltiazem > piperlongumine > piperine. These effects were not different between endothelium-intact and -denuded preparations. In endothelial-denuded preparations, pretreatment with these compounds not only inhibited KCl-induced tonic contractions attenuated calcium chloride (CaCl)-induced ones in a Ca-free medium. Histamine-induced phasic contractions in a Ca-free medium containing intracellular Ca chelator was completely suppressed by selective inositol trisphosphate receptor antagonist and piperlongumine, whereas piperine or diltiazem do not have the same effect. These findings suggest that piperine and piperlongumine similar to diltiazem cause vasorelaxation by inhibiting both KCl- and CaCl-induced contractions in coronary arteries, possibly through the inhibition of voltage-dependent Ca channels. Piperlongumine inhibits histamine-induced contractions in a Ca-free medium, which is associated with the intracellular Ca signaling pathway, suggesting that the relaxant effect of piperlongumine differs from that of piperine.
Topics: Animals; Swine; Diltiazem; Coronary Vessels; Fruit; Calcium Chloride; Histamine; Piper; Calcium; Potassium Chloride; Muscle Contraction
PubMed: 37989300
DOI: 10.1248/bpb.b23-00694 -
RSC Advances Nov 2023Diltiazem (DTZ) is one of the most effective medications for treating cardiovascular diseases. It has been widely used for the treatment of angina pectoris, hypertension...
Diltiazem (DTZ) is one of the most effective medications for treating cardiovascular diseases. It has been widely used for the treatment of angina pectoris, hypertension and some types of arrhythmia. The development and application of a modified carbon paste sensor with improved detection limits for the potentiometric determination of diltiazem are the main goals of the current study. Sensitivity, long-term stability, reproducibility and improving the electrochemical performance are among the characteristics that have undergone careful examination. A modified carbon paste sensor based on β-cyclodextrin (β-CD) as ionophore, a lipophilic anionic additive (NaTPB) and a ZnO-decorated polyaniline/coal nanocomposite (ZnO@PANI/C) dissolved in dibutyl phthalate plasticizer, exhibited the best performance and Nernstian slope. The ZnO@PANI/C based sensor succeeded in lowering the detection limit to 5.0 × 10 through the linear range 1.0 × 10 to 1.0 × 10 mol L with fast response time ≤ 10.0 s. The prepared nanomaterial was characterized using X-ray diffraction (XRD), Fourier transform infrared (FT-IR) spectroscopy and scanning electron microscopy (SEM). The surface properties of the proposed sensor were characterized by electrochemical impedance spectroscopy (EIS). The selectivity behavior of the investigated sensor was tested against a drug with similar chemical structure and biologically important blood electrolytes (Na, K, Mg, and Ca). The proposed analytical method was applied for DTZ analysis in pure drug, pharmaceutical products and industrial water samples with excellent recovery data.
PubMed: 38035231
DOI: 10.1039/d3ra06849h -
Case Reports in Dermatological Medicine 2024Acute generalized exanthematous pustulosis (AGEP) is a rare, acute skin eruption characterized by the development of numerous nonfollicular sterile pustules. Most cases...
Acute generalized exanthematous pustulosis (AGEP) is a rare, acute skin eruption characterized by the development of numerous nonfollicular sterile pustules. Most cases are caused by drug reactions, among which Diltiazem has been incriminated. Herein, we present an 83-year-old female who presented for evaluation of generalized skin rash 3 days after initiation of Diltiazem. She was eventually diagnosed with AGEP, Diltiazem was discontinued, and systemic steroids were administered with the resolution of symptoms. This case report has the objective of encouraging clinicians to include AGEP in the differential diagnosis of skin eruption following the initiation of Diltiazem.
PubMed: 38596598
DOI: 10.1155/2024/9547206 -
Diagnostics (Basel, Switzerland) Mar 2024Patients with immune-mediated rheumatic disease-related calcinosis comprise a subgroup at risk of encountering a more severe clinical outcome. Early assessment is...
Patients with immune-mediated rheumatic disease-related calcinosis comprise a subgroup at risk of encountering a more severe clinical outcome. Early assessment is pivotal for preventing overall disease progression, as calcinosis is commonly overlooked until several years into the disease and is considered as a 'non-lethal' manifestation. This single-center retrospective study explored the prevalence, clinical associations, and impact on survival of subcutaneous calcinosis in 86 patients with immune-mediated rheumatic diseases (IMRD). Calcinosis predominantly appeared in individuals with longstanding disease, particularly systemic sclerosis (SSc), constituting 74% of cases. Smaller calcinosis lesions (≤1 cm) were associated with interstitial lung disease, musculoskeletal involvement, and digital ulcerations, while larger lesions (≥4 cm) were associated with malignancy, severe peripheral artery disease, and systemic arterial hypertension. The SSc calcinosis subgroup exhibited a higher mean adjusted European Scleroderma Study Group Activity Index score than those without. However, survival rates did not significantly differ between the two groups. Diltiazem was the most commonly used treatment, and while bisphosphonates reduced complications related to calcinosis, complete resolution was not achieved. The findings underscore current limitations in diagnosing, monitoring, and treating calcinosis, emphasizing the need for further research and improved therapeutic strategies to improve patient care and outcomes.
PubMed: 38535057
DOI: 10.3390/diagnostics14060637 -
RSC Advances Jan 2024The thermodynamic properties and dissolution of indomethacin (INM) were analyzed as models for poorly water-soluble drugs. Physical mixtures of the most stable γ-form...
Quantification of crystallinity during indomethacin crystalline transformation from α- to γ-polymorphic forms and of the thermodynamic contribution to dissolution in aqueous buffer and solutions of solubilizer.
The thermodynamic properties and dissolution of indomethacin (INM) were analyzed as models for poorly water-soluble drugs. Physical mixtures of the most stable γ-form and metastable α-form of INM at various proportions were prepared, and their individual signal intensities proportional to their mole fractions were observed using X-ray powder diffraction and Fourier transform infrared spectrometry at standard temperature. The endothermic signals of the α-form, with a melting point of 426 K, and that of the γ-form, with a melting point of 433 K, were obtained by differential scanning calorimetry (DSC). Furthermore, an exothermic DSC peak of the α/γ-phase transition at approximately 428 K was obtained. As we computed the melting entropy of the α-form and that of its transformation, the frequency of the transition was quantitatively determined, which indicated the maximum of the α/γ-phase transition at an α-form proportion of 68%. Subsequently, the thermodynamic contributions of the α- and γ-forms were analyzed using a Van't Hoff plot for solubility in aqueous solutions at pH 6.8. The dissolution enthalpies for α- and γ-forms were 28.2 and 31.2 kJ mol, respectively, which are in agreement with the quantitative contribution predicted by the product of the temperature and melting entropy. The contribution of melting entropy was conserved in different dissolution processes with aqueous solvents containing lidocaine, diltiazem, l-carnosine, and aspartame as solubilizers; their γ-form Setschenow coefficients were -39.6, +82.9, -17.3, and +23.2, whereas those of the α-form were -39.7, +80.4, -16.7, and +22.7, respectively. We conclude that the dissolution ability of the solid state and solubilizers indicate their additivity independently.
PubMed: 38292264
DOI: 10.1039/d3ra08481g -
Pharmaceutics Feb 2024Human serum alpha-1-acid glycoprotein (AAG) is an acute-phase plasma protein involved in the binding and transport of many drugs, especially basic and lipophilic...
Human serum alpha-1-acid glycoprotein (AAG) is an acute-phase plasma protein involved in the binding and transport of many drugs, especially basic and lipophilic substances. The sialic acid groups that terminate the N-glycan chains of AAG have been reported to change in response to numerous health conditions and may have an impact on the binding of drugs to AAG. In this study, we quantified the binding between native and desialylated AAG and seven drugs from different pharmacotherapeutic groups (carvedilol, diltiazem, dipyridamole, imipramine, lidocaine, propranolol, vinblastine) using microscale thermophoresis (MST). This method was chosen due to its robustness and high sensitivity, allowing precise quantification of molecular interactions based on the thermophoretic movement of fluorescent molecules. Detailed glycan analysis of native and desialylated AAG showed over 98% reduction in sialic acid content for the enzymatically desialylated AAG. The MST results indicate that desialylation generally alters the binding affinity between AAG and drugs, leading to either an increase or decrease in values, probably due to conformational changes of AAG caused by the different sialic acid content. This effect is also reflected in an increased denaturation temperature of desialylated AAG. Our findings indicate that desialylation impacts free drug concentrations differently, depending on the binding affinity of the drug with AAG relative to human serum albumin (HSA). For drugs such as dipyridamole, lidocaine, and carvedilol, which have a higher affinity for AAG, desialylation significantly changes free drug concentrations. In contrast, drugs such as propranolol, imipramine, and vinblastine, which have a strong albumin binding, show only minimal changes. It is noteworthy that the free drug concentration of dipyridamole is particularly sensitive to changes in AAG concentration and glycosylation, with a decrease of up to 15% being observed, underscoring the need for dosage adjustments in personalized medicine.
PubMed: 38399284
DOI: 10.3390/pharmaceutics16020230 -
Journal of Pharmacological Sciences Nov 2023We examined whether U46619 (a prostanoid TP receptor agonist) could enhance the contractions of guinea pig urinary bladder smooth muscle (UBSM) in response to...
Pharmacological study on the enhancing effects of U46619 on guinea pig urinary bladder smooth muscle contraction induced by acetylcholine and α,β-methylene ATP and the possible involvement of protein kinase C.
We examined whether U46619 (a prostanoid TP receptor agonist) could enhance the contractions of guinea pig urinary bladder smooth muscle (UBSM) in response to acetylcholine (ACh) and an ATP analog (α,β-methylene ATP (αβ-MeATP)) through stimulation of the UBSM TP receptor and whether protein kinase C (PKC) is involved. U46619 (10 M) markedly enhanced UBSM contractions induced by electrical field stimulation and ACh/αβ-MeATP (3 × 10 M each), the potentiation of which was completely suppressed by SQ 29,548 (a TP receptor antagonist, 6 × 10 M). PKC inhibitors did not attenuate the ACh-induced contractions enhanced by U46619 although they partly suppressed the U46619-enhanced, αβ-MeATP-induced contractions. While phorbol 12-myristate 13-acetate (PMA, a PKC activator, 10 M) did not enhance ACh-induced contractions, it enhanced αβ-MeATP-induced contractions, an effect that was completely suppressed by PKC inhibitors. αβ-MeATP-induced contractions, both with and without U46619 enhancement, were strongly inhibited by diltiazem. U46619/PMA enhanced 50 mM KCl-induced contractions, the potentiation of which was partly/completely attenuated by PKC inhibitors. These findings suggest that U46619 potentiates parasympathetic nerve-associated UBSM contractions by stimulating UBSM TP receptors. PKC-increased Ca influx through voltage-dependent Ca channels may partially play a role in purinergic receptor-mediated UBSM contractions enhanced by TP receptor stimulation.
Topics: Guinea Pigs; Animals; Acetylcholine; Urinary Bladder; 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Adenosine Triphosphate; Muscle Contraction; Receptors, Thromboxane
PubMed: 37770153
DOI: 10.1016/j.jphs.2023.08.007 -
World Journal of Clinical Cases Aug 2023Atrial arrhythmias such as paroxysmal supraventricular tachycardia (PSVT) and atrial flutter (AF) are common in the perioperative setting. They commonly resolve...
BACKGROUND
Atrial arrhythmias such as paroxysmal supraventricular tachycardia (PSVT) and atrial flutter (AF) are common in the perioperative setting. They commonly resolve spontaneously. However, occasionally, they may continually progress to fatal arrhythmias or cause complications. Therefore, prompt and appropriate management is important.
CASE SUMMARY
A 46-year-old female patient diagnosed with cervical C6-7 radiculopathy characterized by decreased sensation in the right third, fourth and fifth fingers underwent C6-7 anterior cervical disc fusion surgery. Electrocardiography showed PSVT and ventricular tachycardia during C6-7 disc retraction. However, the patient remained stable. Initial treatment with esmolol and lidocaine for ventricular tachycardia was ineffective. Carotid massage and Valsalva maneuver were attempted but PSVT did not resolve. The surgery was paused, and the patient's fraction of inspired oxygen was set to 100%. Adenosine was administered for pharmacological management of PSVT. The arrhythmia temporarily resolved. However, it then transformed into AF. Diltiazem was administered, which briefly decreased blood pressure, which immediately recovered. Surgery resumed while the patient was in normal sinus rhythm. She was discharged safely on postoperative day 6 without complications or abnormalities. Currently, she is living a healthy life without arrhythmia recurrence.
CONCLUSION
Ganglia associated with cardiac arrhythmias in the surgical site should be identified during cervical spine surgery.
PubMed: 37727714
DOI: 10.12998/wjcc.v11.i24.5789 -
Case Reports in Emergency Medicine 2023The most frequent atrioventricular tachycardia in the emergency room is atrioventricular nodal reentrant tachycardia (AVNRT). The first treatment option for ending...
BACKGROUND
The most frequent atrioventricular tachycardia in the emergency room is atrioventricular nodal reentrant tachycardia (AVNRT). The first treatment option for ending stable narrow QRS complex SVTs is vagal maneuvers and adenosine. When adenosine or vagal maneuvers fail to change a patient's rhythm to normal sinus rhythm, long-acting AV nodal-blocking medications, including nondihydropyridine calcium channel blockers (verapamil and diltiazem), flecainide, or beta-blockers, are employed. Electricity (synchronized cardioversion) is the preferred form of treatment for unstable patients. . A 40-year-old male patient presented to the Emergency Department of Dubti General Hospital, the Afar regional state in Ethiopia, with a complaint of shortness of breath, palpitation, extreme fatigue, and chest pain of a day's duration. His blood pressure was 80/50 mmHg, he had cold extremities and a weak radial pulse, and his apical heart rate was fast, making it difficult to count. His electrocardiogram (ECG) showed paroxysmal supraventricular tachycardia (PSVT) with a heart rate of 200. He was a candidate for electrical cardioversion due to unstable PSVT, but he and his family members refused to give consent. Even though he is not indicated for pharmacologic therapy, none of the commonly used drugs were available at the hospital. We managed him with digoxin, and the outcome was positive.
CONCLUSION
Even though we could not find a clear recommendation regarding the use of digoxin for patients with unstable PSVT (AVNRT), by taking into consideration its negative chronotropic effect and its action to suppress the AV nodal conduction velocity, it may reduce the heart rate, and it can be used as an alternative in such difficult scenarios and a resource-limited setting. But this should be further investigated.
PubMed: 37457790
DOI: 10.1155/2023/7301460 -
Journal of the Anus, Rectum and Colon 2024Lateral internal sphincterotomy is a conventional surgical intervention for chronic anal fissures, yet the potential for postoperative anal incontinence underscores the...
OBJECTIVES
Lateral internal sphincterotomy is a conventional surgical intervention for chronic anal fissures, yet the potential for postoperative anal incontinence underscores the need for an alternative approach. This study aimed to evaluate the outcomes of patients with chronic fissures who underwent a combination of fissurectomy, vertical non-full thickness midline sphincterotomy (VNMS), and mucosal advancement flap (MAF), as a means of mitigating the risk of incontinence.
METHODS
This retrospective analysis included forty-six consecutive patients with chronic anal fissures, unresponsive to topical diltiazem, who underwent fissurectomy combined with VNMS and MAF between April 2018 and May 2023. Primary outcome measures encompassed fissure healing rates. Continence was assessed using the Fecal Incontinence Severity Index (FISI), and manometric assessments were conducted before the procedure and three months postoperatively.
RESULTS
With a median follow-up of 27 months, there were no postoperative complications, and the overall fissure healing rate reached 96% (44/46). At three months post-procedure, FISI scores were reduced to 0, with no instances of fecal soiling. Anal resting pressure exhibited a significant reduction at 3 months [pre-op: 133 (95% CI, 128-150) vs. 3 mo: 109 (95% CI, 100-117) cmHO; = 0.01]. Similarly, maximum anal squeeze pressure showed a significant decrease three months post-surgery [pre-op: 317 cmHO (95% CI, 294-380) vs. 3 mo: 291 cmHO (95% CI, 276-359), = 0.03].
CONCLUSIONS
The combination of fissurectomy, VNMS, and MAF proved to be an effective approach for chronic anal fissures, yielding favorable medium-term outcomes without postoperative anal incontinence.
PubMed: 38689786
DOI: 10.23922/jarc.2023-072