RESUMEN

BACKGROUND: Kounis syndrome is defined as the concurrence of acute coronary syndromes in the setting of allergic or anaphylactic reactions. It primarily affects men aged 40-70 years and is often associated with chest pain. This syndrome is often unrecognized and undiagnosed in clinical practice due to a low level of awareness. Herein, we present a case of type I Kounis syndrome in a young woman without chest pain. CASE PRESENTATION: A 28-year-old Japanese woman with a history of atopic dermatitis received a glycyrrhizin, glutathione, and neurotropin preparation (a preparation of inflamed skin extract from rabbits inoculated with vaccinia virus) at a dermatology clinic to treat pruritus caused by atopic dermatitis. Immediately after the administration, the patient developed abdominal pain and generalized body wheals. The patient was diagnosed with anaphylaxis and was transported to our hospital. She had no chest pain on arrival at our hospital; however, a 12-lead electrocardiogram showed ST elevation in leads I, aVL, V2, and V3, and an echocardiogram showed decreased wall motion in the anterior and lateral walls of the left ventricle. Sublingual nitroglycerin administration improved ST-segment elevation and left ventricular wall motion abnormalities. The patient underwent emergency coronary angiography, which revealed no significant stenosis, and was diagnosed with type I Kounis syndrome. CONCLUSION: Kounis syndrome without chest pain is rare in young women. Since it can be fatal in cases with severe allergic symptoms such as anaphylaxis, the possibility of concurrent acute coronary syndrome should be considered when treating systemic allergic reactions, regardless of age, sex, or the presence or absence of chest symptoms.

Asunto(s)

Síndrome de Kounis , Femenino , Humanos , Síndrome de Kounis/diagnóstico , Síndrome de Kounis/etiología , Síndrome de Kounis/fisiopatología , Síndrome de Kounis/tratamiento farmacológico , Adulto , Angiografía Coronaria , Resultado del Tratamiento , Electrocardiografía , Vasodilatadores/administración & dosificación , Nitroglicerina/administración & dosificación , Anafilaxia/diagnóstico , Anafilaxia/inducido químicamente , Anafilaxia/tratamiento farmacológico , Administración Sublingual

RESUMEN

Sodium serves as one of the primary cations in the central nervous system, playing a crucial role in maintaining normal brain function. In this study, we investigated alterations in sodium concentrations in the brain and/or cerebrospinal fluid across multiple models, including an aging model, a stroke model, a nitroglycerin (NTG)-induced rat migraine model, a familial hemiplegic migraine type 2 (FHM2) mouse model, and a transgenic mouse model of Alzheimer's disease (AD). Our results reveal that older rats exhibited higher sodium concentrations in cerebrospinal fluid (CSF), plasma, and various brain regions compared to their younger counterparts. Additionally, findings from the stroke model demonstrated a significant increase in sodium in the ischemic/reperfused region, accompanied by a decrease in potassium and an elevated sodium/potassium ratio. However, we did not detect significant changes in sodium in the NTG-induced rat migraine model or the FHM2 mouse model. Furthermore, AD transgenic mice showed no significant differences in sodium levels compared to wild-type mice in CSF, plasma, or the hippocampus. These results underscore the nuanced regulation of sodium homeostasis in various neurological conditions and aging, providing valuable insights into potential mechanisms underlying these alterations.

Asunto(s)

Envejecimiento , Enfermedad de Alzheimer , Modelos Animales de Enfermedad , Ratones Transgénicos , Trastornos Migrañosos , Sodio , Accidente Cerebrovascular , Animales , Enfermedad de Alzheimer/metabolismo , Sodio/líquido cefalorraquídeo , Sodio/sangre , Sodio/metabolismo , Ratas , Ratones , Masculino , Accidente Cerebrovascular/metabolismo , Trastornos Migrañosos/metabolismo , Trastornos Migrañosos/inducido químicamente , Trastornos Migrañosos/sangre , Humanos , Nitroglicerina/farmacología , Daño por Reperfusión/metabolismo , Encéfalo/metabolismo , Ratas Sprague-Dawley , Migraña con Aura

RESUMEN

Systemic vasodilating agents like nitroglycerin (NG) or iloprost (Ilo) show beneficial effects on intestinal microcirculation during sepsis, which could be attenuated by activation of the sympathetic nervous system or systemic side effects of vasodilating agents. This exploratory study aimed to investigate the effects of topically administered vasodilators and the parasympathetic drug carbachol on colonic microcirculatory oxygenation (µHbO2), blood flow (µFlow) and mitochondrial respiration. A total of 120 male Wistar rats were randomly assigned to twelve groups and underwent either colon ascendens stent peritonitis (CASP) or sham surgery. After 24 h, animals received the following therapeutic regimes: (1) balanced full electrolyte solution, (2) carbachol, (3) NG, (4) Ilo, (5) NG + carbachol, and (6) Ilo + carbachol. Mitochondrial respiration was measured in colon homogenates by respirometry. In sham animals, NG (-13.1%*) and Ilo (-10.5%*) led to a decrease in µHbO2. Additional application of carbachol abolished this effect (NG + carbachol: -4.0%, non-significant; Ilo + carbachol: -1.4%, non-significant). In sepsis, carbachol reduced µHbO2 when applied alone (-10.5%*) or in combination with NG (-17.6%*). Thus, the direction and degree of this effect depend on the initial pathophysiologic condition.

Asunto(s)

Sistema Nervioso Autónomo , Carbacol , Microcirculación , Mitocondrias , Ratas Wistar , Sepsis , Vasodilatadores , Animales , Microcirculación/efectos de los fármacos , Sepsis/tratamiento farmacológico , Sepsis/fisiopatología , Masculino , Ratas , Vasodilatadores/farmacología , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Sistema Nervioso Autónomo/efectos de los fármacos , Sistema Nervioso Autónomo/fisiopatología , Carbacol/farmacología , Colon/efectos de los fármacos , Colon/irrigación sanguínea , Colon/metabolismo , Nitroglicerina/farmacología

RESUMEN

Iatrogenic acute limb ischaemia (ALI) in neonates is a rare but severe event with potentially deleterious outcomes. In the neonatal intensive care unit, this risk is increased due to the high rate of catheterisation procedures. ALI management includes pharmacological and non-pharmacological interventions, but no commonly accepted clinical guidelines are available. In the present case, a peripheral catheter was erroneously placed in the left brachial artery of a term infant, causing blockage and ischaemia in the limb. The catheter was immediately removed, the affected limb was elevated and warm compresses were applied to the contralateral limb. The patient was treated with fresh frozen plasma, heparin, iloprost and topical nitroglycerin. Three nerve block procedures were also performed. At 6-8 days of age, significant improvement was observed. The patient was discharged at 17 days of age with near-complete resolution, whereas complete resolution was observed at postdischarge follow-up.

Asunto(s)

Enfermedad Iatrogénica , Isquemia , Humanos , Recién Nacido , Isquemia/etiología , Isquemia/terapia , Cateterismo Periférico/efectos adversos , Arteria Braquial/diagnóstico por imagen , Heparina/administración & dosificación , Heparina/uso terapéutico , Masculino , Nitroglicerina/administración & dosificación , Nitroglicerina/uso terapéutico , Femenino , Vasodilatadores/uso terapéutico , Vasodilatadores/administración & dosificación , Iloprost/administración & dosificación , Iloprost/uso terapéutico , Enfermedad Aguda , Bloqueo Nervioso/métodos

RESUMEN

BACKGROUND: Nitroglycerin has been of considerable interest as a treatment for ischaemic stroke. Recent clinical trials with nitroglycerin transdermal patches during the acute phase of stroke failed to improve functional outcomes. Systematic review and meta-analysis of the effectiveness of nitroglycerin in preclinical models of ischaemic stroke has not previously been reported, despite several clinical trials. OBJECTIVE: To conduct a systematic review and meta-analysis of preclinical evidence regarding the effect of nitroglycerin on infarct volume in animal models of ischaemic stroke. SUMMARY OF REVIEW: The protocol was registered in PROSPERO (CRD42023432644). Our search identified 238 publications. Three publications met inclusion criteria (including 10 comparisons of infarct size). Study quality was modest (median 6 out of 9), with no evidence of publication bias. Nitroglycerin did not significantly reduce infarct volume (NMD point estimate 20.2 % reduction, 95 % CI -1.52-52.7 %, p = 0.068). Subgroup analysis suggested greater efficacy of nitroglycerin with direct intracarotid administration to the ischaemic territory at the time of reperfusion. CONCLUSIONS: A small number of studies (three) were included in this review. Overall, nitroglycerin did not reduce infarct volume in experimental stroke models. However, nitroglycerin may be of benefit when administered directly into the ischaemic territory. Given nitroglycerin's short half-life, we propose this route may minimise harmful reduction of cerebral perfusion pressure resulting from hypotension following systemic administration.

Asunto(s)

Isquemia Encefálica , Nitroglicerina , Nitroglicerina/administración & dosificación , Nitroglicerina/farmacología , Nitroglicerina/uso terapéutico , Animales , Isquemia Encefálica/tratamiento farmacológico , Vasodilatadores/uso terapéutico , Vasodilatadores/farmacología , Vasodilatadores/administración & dosificación , Modelos Animales de Enfermedad

RESUMEN

AIMS: The study evaluated the positivity rate, haemodynamic responses, and prognosis in terms of syncopal recurrence among patients with situational syncope (SS) stratified according to the underlying situational triggers. METHODS AND RESULTS: We retrospectively evaluated all consecutive patients with SS who underwent nitroglycerine (NTG)-potentiated head-up tilt test (HUTT) at Syncope Unit of the University of Campania 'Luigi Vanvitelli'-Monaldi Hospital from 1 March 2017 to 1 May 2023. All patients were followed for at least one year. The study population was divided according to the underlying triggers (micturition, swallow, defaecation, cough/sneeze, post-exercise). Two hundred thirty-six SS patients (mean age 50 ± 19.3 years; male 63.1%) were enrolled; among them, the situational trigger was micturition in 109 patients (46.2%); swallow in 32 (13.6%) patients; defaecation in 35 (14.8%) patients; post-exercise in 41 (17.4%) patients; and cough/sneeze in 17 (7.2%) patients. There were no significant differences in baseline clinical characteristics and HUTT responses between different situational triggers. The Kaplan-Meier analysis did not show a statistically different rate of syncope recurrence across patients stratified by baseline situational triggers (log-rank P = 0.21). CONCLUSION: Situational syncope appears to be a homogenous syndrome, and different triggers do not impact the HUTT response or syncope recurrence at 1 year.

Asunto(s)

Recurrencia , Síncope , Pruebas de Mesa Inclinada , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Síncope/fisiopatología , Síncope/diagnóstico , Síncope/etiología , Pronóstico , Anciano , Adulto , Tos/fisiopatología , Tos/diagnóstico , Deglución , Nitroglicerina/administración & dosificación , Valor Predictivo de las Pruebas , Hemodinámica , Factores de Riesgo

RESUMEN

BACKGROUND: Migraine is a neurological disorder characterized by complex, widespread, and sudden attacks with an unclear pathogenesis, particularly in chronic migraine (CM). Specific brain regions, including the insula, amygdala, thalamus, and cingulate, medial prefrontal, and anterior cingulate cortex, are commonly activated by pain stimuli in patients with CM and animal models. This study employs fluorescence microscopy optical sectioning tomography (fMOST) technology and AAV-PHP.eB whole-brain expression to map activation patterns of brain regions in CM mice, thus enhancing the understanding of CM pathogenesis and suggesting potential treatment targets. METHODS: By repeatedly administering nitroglycerin (NTG) to induce migraine-like pain in mice, a chronic migraine model (CMM) was established. Olcegepant (OLC) was then used as treatment and its effects on mechanical pain hypersensitivity and brain region activation were observed. All mice underwent mechanical withdrawal threshold, light-aversive, and elevated plus maze tests. Viral injections were administered to the mice one month prior to modelling, and brain samples were collected 2 h after the final NTG/vehicle control injection for whole-brain imaging using fMOST. RESULTS: In the NTG-induced CMM, mechanical pain threshold decreased, photophobia, and anxiety-like behavior were observed, and OLC was found to improve these manifestations. fMOST whole-brain imaging results suggest that the isocortex-cerebral cortex plate region, including somatomotor areas (MO), somatosensory areas (SS), and main olfactory bulb (MOB), appears to be the most sensitive area of activation in CM (P < 0.05). Other brain regions such as the inferior colliculus (IC) and intermediate reticular nucleus (IRN) were also exhibited significant activation (P < 0.05). The improvement in migraine-like symptoms observed with OLC treatment may be related to its effects on these brain regions, particularly SS, MO, ansiform lobule (AN), IC, spinal nucleus of the trigeminal, caudal part (Sp5c), IRN, and parvicellular reticular nucleus (PARN) (P < 0.05). CONCLUSIONS: fMOST whole-brain imaging reveals c-Fos + cells in numerous brain regions. OLC improves migraine-like symptoms by modulating brain activity in some brain regions. This study demonstrates the activation of the specific brain areas in NTG-induced CMM and suggests some regions as a potential treatment mechanism according to OLC.

Asunto(s)

Encéfalo , Modelos Animales de Enfermedad , Trastornos Migrañosos , Nitroglicerina , Animales , Nitroglicerina/toxicidad , Nitroglicerina/farmacología , Nitroglicerina/administración & dosificación , Trastornos Migrañosos/inducido químicamente , Trastornos Migrañosos/diagnóstico por imagen , Trastornos Migrañosos/metabolismo , Trastornos Migrañosos/tratamiento farmacológico , Ratones , Encéfalo/diagnóstico por imagen , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Masculino , Proteínas Proto-Oncogénicas c-fos/metabolismo , Ratones Endogámicos C57BL , Mapeo Encefálico , Vasodilatadores/farmacología , Vasodilatadores/administración & dosificación , Umbral del Dolor/efectos de los fármacos

RESUMEN

OBJECTIVES: To investigate if daily treatment with glyceryl trinitrate (GTN) ointment, over 24 weeks combined with a 12-week eccentric exercise programme is more effective for chronic mid-portion Achilles tendinopathy than placebo ointment and eccentric exercise. METHODS: This was a single-site randomised double-blind placebo-controlled trial at an acute hospital, Dublin, Ireland. Patients with chronic mid-portion Achilles tendinopathy were randomised to either 24 weeks of daily GTN ointment or placebo ointment. Both groups received an identical 12-week eccentric exercise programme. The primary outcome measure was the Victorian Institute of Sport Assessment-Achilles (VISA-A) questionnaire at 24 weeks, which measures pain, function and activity. Secondary outcomes included pain severity, self-reported physical function, calf muscle function, pressure pain thresholds and ultrasound changes. Statistical analyses were performed according to intention-to-treat principles. RESULTS: 76 patients (30 women; 46 men, mean age±SD, 45.6±8.2 years) were recruited for the trial. Significant improvements in VISA-A scores occurred in both groups at 6-week, 12-week and 24-week follow-up. The increase was not significantly different between groups, adjusted mean between-group difference from baseline to week 6, -1.33 (95% CI -6.96 to 4.31); week 12, -1.25 (95% CI -8.0 to 5.49) and week 24, -3.8 (95% CI -10.6 to 3.0); negative values favour GTN. There was no significant between-group difference in any of the secondary outcome measures at 6, 12 and 24 weeks. CONCLUSIONS: Adding daily GTN ointment over 24 weeks to a 12-week eccentric exercise programme did not improve pain, function and activity level in patients with chronic mid-portion Achilles tendinopathy when compared with placebo ointment.

Asunto(s)

Tendón Calcáneo , Terapia por Ejercicio , Nitroglicerina , Pomadas , Tendinopatía , Humanos , Nitroglicerina/administración & dosificación , Masculino , Femenino , Tendinopatía/terapia , Tendinopatía/tratamiento farmacológico , Método Doble Ciego , Persona de Mediana Edad , Adulto , Resultado del Tratamiento , Terapia por Ejercicio/métodos , Terapia Combinada , Vasodilatadores/administración & dosificación , Dimensión del Dolor

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Herb-herb combination has been used to maximize the therapeutic efficacy in the theory of traditional Chinese medicine. Chuanxiong rhizoma (called Chuanxiong in Chinese, CX) and Cyperi rhizoma (called Xiangfu in Chinese, XF) have been used alone or in combination (CRCR) to treat migraine dating back to Eastern Jin Dynasty (AD317) of China. But no data demonstrate the possible necessities or advantages of combining CX and XF for migraine. AIM OF THE STUDY: This study explores the combination mechanism based on pharmacodynamics and pharmacokinetics. MATERIALS AND METHODS: A nitroglycerin-induced acute migraine model in rats was used to evaluate the anti-migraine effects of CRCR and the individual herbs using behavior, real time polymerase chain reaction and Western blot experiments. The absorption characteristics of active components involved in the anti-migraine action were analyzed by UPLC-MS/MS. RESULTS: CX and CRCR significantly reversed the abnormal levels of vasoactive substances (5-HT, CGRP, MMP-2 and MMP-9) to normal levels, but XF did not. XF and CRCR significantly decreased the pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-a), and increased the anti-inflammatory cytokines (IL-4 and IL-10). CRCR significantly decreased the mRNA expression levels of c-fos, iNos and nNos, and the corresponding protein expression levels of c-Fos, iNOS, and nNOS. CRCR inhibited NOS/NO pathway by downregulating the expression levels of NOS and NO. Furthermore, CRCR significantly increased the intestinal absorption rate and amount, and changed the pharmacokinetic parameters of active components in comparison with the individual herbs. CONCLUSIONS: CX had an advantage in regulating vasoactive substances, and XF focused on regulating inflammatory cytokines. CRCR is more effective in treating migraine than the individual herbs by depending on the synergistic action of CX and XF. This research provided some critical evidences on synergistic action between herb-herb interactions, and revealed the potential advantages of herb-herb combination in traditional Chinese medicine.

Asunto(s)

Sinergismo Farmacológico , Medicamentos Herbarios Chinos , Trastornos Migrañosos , Ratas Sprague-Dawley , Animales , Trastornos Migrañosos/tratamiento farmacológico , Masculino , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/farmacocinética , Nitroglicerina/farmacología , Ratas , Rizoma , Modelos Animales de Enfermedad

RESUMEN

BACKGROUND: Nocturnal hemodialysis (nHD) restores the attenuated brachial artery vasodilator responsiveness of patients receiving conventional intermittent hemodialysis (iHD). Its impact on coronary vasodilatation is unknown. METHODS: We evaluated 25 patients on hemodialysis who fulfilled transplant criteria: 15 on iHD (4-hour sessions, 3 d/wk) and 10 on nHD (≈40 h/wk over 8-10-hour sessions) plus 6 control participants. Following diagnostic angiography, left anterior descending (LAD) coronary flow reserve and mean luminal diameter were quantified at baseline and during sequential intracoronary administration of adenosine (infusion and bolus), nitroglycerin (bolus), acetylcholine (infusion), acetylcholine coinfused with vitamin C, and, finally, sublingual nitroglycerin. RESULTS: Coronary flow reserve in those receiving nHD was augmented relative to iHD (3.28±0.26 versus 2.17±0.12 [mean±SEM]; P<0.03) but attenuated, relative to controls (4.80±0.63; P=0.011). Luminal dilatations induced by intracoronary adenosine and nitroglycerin were similar in nHD and controls but blunted in the iHD cohort (P<0.05 versus both). ACh elicited vasodilatation in controls but constriction in both dialysis groups (both P<0.05, versus control); vitamin C coinfusion had no effect. Sublingual nitroglycerin increased mid-left anterior descending diameter and reduced mean arterial pressure in controls (+15.2±2.68%; -16.00±1.60%) and in nHD recipients (+14.78±5.46%; -15.82±1.32%); iHD responses were markedly attenuated (+1.9±0.86%; -5.89±1.41%; P<0.05, all comparisons). CONCLUSIONS: Coronary and systemic vasodilator responsiveness to both adenosine and nitroglycerin is augmented in patients receiving nHD relative to those receiving iHD, whereas vasoconstrictor responsiveness to acetylcholine does not differ. By improving coronary conduit and microvascular function, nHD may reduce the cardiovascular risk of patients on dialysis.

Asunto(s)

Nitroglicerina , Diálisis Renal , Vasodilatación , Vasodilatadores , Humanos , Femenino , Masculino , Diálisis Renal/métodos , Persona de Mediana Edad , Vasodilatadores/administración & dosificación , Vasodilatadores/farmacología , Vasodilatación/efectos de los fármacos , Vasodilatación/fisiología , Nitroglicerina/farmacología , Nitroglicerina/administración & dosificación , Anciano , Circulación Coronaria/efectos de los fármacos , Circulación Coronaria/fisiología , Acetilcolina/farmacología , Acetilcolina/administración & dosificación , Fallo Renal Crónico/terapia , Fallo Renal Crónico/fisiopatología , Arteria Braquial/efectos de los fármacos , Arteria Braquial/fisiopatología , Adenosina/administración & dosificación , Vasos Coronarios/diagnóstico por imagen , Vasos Coronarios/fisiopatología , Vasos Coronarios/efectos de los fármacos , Angiografía Coronaria

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Alpha 7 nicotinic acetylcholine receptor (α7nAChR)-mediated astrocytic activation is closely related to central sensitization of chronic migraine (CM). Xiongzhi Dilong decoction (XZDL), originated from Xiongzhi Shigao decoction of Yi-zong-jin-jian, has been confirmed to relieve CM in experiment and clinic. However, its underlying mechanism for treating CM has not been elucidated. AIM OF THE STUDY: To reveal the underlying mechanisms of XZDL to alleviate CM in vivo focusing mainly on α7nAChR-mediated astrocytic activation and central sensitization in TNC. MATERIALS AND METHODS: CM rat model was established by subcutaneous injection of nitroglycerin (NTG) recurrently, and treated with XZDL simultaneously. Migraine-like behaviors of rats (ear redness, head scratching, and cage climbing) and pain-related reactions (mechanical hind-paw withdrawal threshold) of rats were evaluated before and after NTG injection and XZDL administration at different points in time for nine days. The immunofluorescence single and double staining were applied to detect the levels of CGRP, c-Fos, GFAP and α7nAChR in NTG-induced CM rats. ELISA kits were employed to quantify levels of TNF-α, IL-1ß, and IL-6 in medulla oblongata of CM rats. The expression levels of target proteins were examined using western blotting. Finally, methyllycaconitine citrate (MLA, a specific antagonist of α7nAChR) was applied to further validate the mechanisms of XZDL in vivo. RESULTS: XZDL significantly attenuated the pain-related behaviors of the NTG-induced CM rats, manifesting as constraints of aberrant migraine-like behaviors including elongated latency of ear redness and decreased numbers of head scratching and cage climbing, and increment of mechanical withdrawal threshold. Moreover, XZDL markedly lowered levels of CGRP and c-Fos, as well as inflammatory cytokines (IL-1ß, IL-6 and TNF-α) in CM rats. Furthermore, XZDL significantly enhanced α7nAChR expression and its co-localization with GFAP, while markedly inhibited the expression of GFAP and the activation of JAK2/STAT3/NF-κB pathway in the TNC of CM rats. Finally, blocking α7nAChR with MLA reversed the effects of XZDL on astrocytic activation, central sensitization, and the pain-related behaviors in vivo. CONCLUSION: XZDL inhibited astrocytic activation and central sensitization in NTG-induced CM rats by facilitating α7nAChR expression and suppressing JAK2/STAT3/NF-κB pathway, implying that the regulation of α7nAChR-mediated astrocytic activation represents a novel mechanism of XZDL for relieving CM.

Asunto(s)

Astrocitos , Medicamentos Herbarios Chinos , Trastornos Migrañosos , Receptor Nicotínico de Acetilcolina alfa 7 , Animales , Masculino , Ratas , Receptor Nicotínico de Acetilcolina alfa 7/metabolismo , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Enfermedad Crónica , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/inducido químicamente , Trastornos Migrañosos/metabolismo , Nitroglicerina/farmacología , Ratas Sprague-Dawley

RESUMEN

BACKGROUND: Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), with an incidence of approximately 9.7% according to some literature reviews. Recent clinical guidelines propose that glyceryl trinitrate (GTN) can reduce the incidence of post-ERCP pancreatitis (PEP). However, currently, no guidelines provide an exact opinion on GTN and nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent post-ERCP pancreatitis. OBJECTIVE: A meta-analysis was performed of published, full-length, randomized controlled trials (RCTs) evaluating the effects of prophylactic use of GTN, including GTN alone or GTN in combination with NSAIDs, on the prevention of PEP. METHODS: Literature searches were conducted using PubMed, Embase, Web of Science, and The Cochrane Library. Search terms included "endoscopic retrograde cholangiopancreatography" OR "ERCP," "OR 'PEP' OR 'post-endoscopic retrograde cholangiopancreatography pancreatitis', pancreatitis," "GTN" OR "glyceryl trinitrate" OR "nitroglycerin," "NSAIDs" OR "Nonsteroidal Anti-inflammatory Drugs" and limited to RCT. RESULTS: A total of 10 RCTs comprising 3240 patients undergoing ERCP were included. Meta-analysis revealed that the administration of GTN was associated with a significant reduction in the overall incidence of PEP. Moreover, PEP incidence was significantly lower in the GTN combined with the NSAIDs group than in the GTN alone group. GTN alone or GTN combined with NSAIDs may not reduce the severity of PEP (risk ratio = 0.64; 95% confidence interval: 0.41-0.99; P = .04). The difference in incidence between the 2 groups is 1.01% (6/594) in the GTN with NSAIDs group and 2.36% (14/592) in the placebo group. CONCLUSION: GTN has a significant benefit in preventing postoperative ERCP pancreatitis (P < .001). And neither GTN nor GTN plus NSAIDs reduces the incidence of non-mild ERCP postoperative pancreatitis. These conclusions need to be confirmed by high-quality randomized controlled studies with multicenter, large samples, and long-term follow-up.

Asunto(s)

Antiinflamatorios no Esteroideos , Colangiopancreatografia Retrógrada Endoscópica , Quimioterapia Combinada , Nitroglicerina , Pancreatitis , Ensayos Clínicos Controlados Aleatorios como Asunto , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Humanos , Antiinflamatorios no Esteroideos/uso terapéutico , Antiinflamatorios no Esteroideos/administración & dosificación , Nitroglicerina/uso terapéutico , Nitroglicerina/administración & dosificación , Pancreatitis/prevención & control , Pancreatitis/etiología , Vasodilatadores/uso terapéutico , Vasodilatadores/administración & dosificación

RESUMEN

BACKGROUND: Conventional anesthesia used to reduce central venous pressure (CVP) during hepatectomy includes fluid restriction and vasodilator drugs, which can lead to a reduction in blood perfusion in vital organs and may counteract the benefits of low blood loss. In this study, we hypothesized that milrinone is feasible and effective in controlling low CVP (LCVP) during laparoscopic hepatectomy (LH). Compared with conventional anesthesia such as nitroglycerin, milrinone is beneficial in terms of intraoperative blood loss, surgical environment, hemodynamic stability, and patients' recovery. METHODS: In total, 68 patients undergoing LH under LCVP were randomly divided into the milrinone group (n = 34) and the nitroglycerin group (n = 34). Milrinone was infused with a loading dose of 10 µg/kg followed by a maintenance dose of 0.2-0.5 µg/kg/min and nitroglycerin was administered at a rate of 0.2-0.5 µg/kg/min until the liver lesions were removed. The characteristics of patients, surgery, intraoperative vital signs, blood loss, the condition of the surgical field, the dosage of norepinephrine, perioperative laboratory data, and postoperative complications were compared between groups. Blood loss during LH was considered the primary outcome. RESULTS: Blood loss during hepatectomy and total blood loss were significantly lower in the milrinone group compared with those in the nitroglycerin group (P < 0.05). Both the nitroglycerin group and milrinone group exerted similar CVP (P > 0.05). Nevertheless, the milrinone group had better surgical field grading during liver resection (P < 0.05) and also exhibited higher cardiac index and cardiac output during the surgery (P < 0.05). Significant differences were also found in terms of fluids administered during hepatectomy, urine volume during hepatectomy, total urine volume, and norepinephrine dosage used in the surgery between the two groups. The two groups showed a similar incidence of postoperative complications (P > 0.05). CONCLUSION: Our findings indicate that the intraoperative infusion of milrinone can help in maintaining an LCVP and hemodynamic stability during LH while reducing intraoperative blood loss and providing a better surgical field compared with nitroglycerin. TRIAL REGISTRATION: ChiCTR2200056891,first registered on 22/02/2022.

Asunto(s)

Pérdida de Sangre Quirúrgica , Presión Venosa Central , Hepatectomía , Laparoscopía , Milrinona , Nitroglicerina , Vasodilatadores , Humanos , Milrinona/administración & dosificación , Nitroglicerina/administración & dosificación , Hepatectomía/métodos , Masculino , Femenino , Método Doble Ciego , Laparoscopía/métodos , Persona de Mediana Edad , Presión Venosa Central/efectos de los fármacos , Vasodilatadores/administración & dosificación , Pérdida de Sangre Quirúrgica/prevención & control , Anciano , Adulto , Complicaciones Posoperatorias/prevención & control

RESUMEN

Objectives: To compare the outcome of botulinum toxin injection with and without glyceryl trinitrate with respect to postoperative pain and healing in the treatment of anal fissures. METHODS: The prospective, comparative study was conducted at the Department of General Surgery, Mayo Hospital, Lahore, Pakistan, from September 1, 2021, to August 31, 2022, and comprised adult chronic anal fissure patients of either gender. They were randomised using the lottery method into group A which received botulinum toxin injection, and group B which received botulinum toxin injection plus 1g of 0.2% topical glyceryl trinitrate cream. Post-operative pain was measured 24 hours after the procedure using the visual analogue scale. Healing was assessed by examining the wound for the appearance of granulation tissue 4 weeks post-procedure. Data was analysed using SPSS 26. RESULTS: Of the 88 patients, 44(50%) were in group A; 32(72.7%) males and 12(27.3%) females with mean age 33.91±14.8 years. There were 44(50%) patients in group B; 35(79.5%) males and 9(20.5%) females with mean age range 36.33±14.9 years. The mean postoperative pain at 24 hours in group A was 4.67±1.16 and it was 3.06±0.65 in group B (p=0.009). In group A, 23(69.7%) patients showed complete healing at 4 weeks compared to 30(90.9%) in group B (p=0.030). CONCLUSIONS: Botulinum toxin injection with glyceryl trinitrate could be considered as first line of treatment for chronic anal fissure in patients who refuse surgery and with previous sphincter surgery.

Asunto(s)

Toxinas Botulínicas Tipo A , Fisura Anal , Nitroglicerina , Dolor Postoperatorio , Cicatrización de Heridas , Humanos , Fisura Anal/tratamiento farmacológico , Fisura Anal/cirugía , Femenino , Masculino , Nitroglicerina/administración & dosificación , Nitroglicerina/uso terapéutico , Adulto , Dolor Postoperatorio/tratamiento farmacológico , Toxinas Botulínicas Tipo A/administración & dosificación , Toxinas Botulínicas Tipo A/uso terapéutico , Persona de Mediana Edad , Enfermedad Crónica , Cicatrización de Heridas/efectos de los fármacos , Estudios Prospectivos , Adulto Joven , Vasodilatadores/administración & dosificación , Vasodilatadores/uso terapéutico , Fármacos Neuromusculares/administración & dosificación , Fármacos Neuromusculares/uso terapéutico , Quimioterapia Combinada , Resultado del Tratamiento , Dimensión del Dolor

RESUMEN

BACKGROUND: Nurses adjust intravenous nitroglycerin infusions to provide acute relief for angina by manually increasing or decreasing the dosage. However, titration can pose challenges, as excessively high doses can lead to hypotension, and low doses may result in inadequate pain relief. Clinical decision support systems (CDSSs) that predict changes in blood pressure for nitroglycerin dose adjustments may assist nurses with titration. OBJECTIVE: This study aimed to design a user interface for a CDSS for nitroglycerin dose titration (Nitroglycerin Dose Titration Decision Support System [nitro DSS]). METHODS: A user-centered design (UCD) approach, consisting of an initial qualitative study with semistructured interviews to identify design specifications for prototype development, was used. This was followed by three iterative rounds of usability testing. Nurses with experience titrating nitroglycerin infusions in coronary care units participated. RESULTS: A total of 20 nurses participated, including 7 during the qualitative study and 15 during usability testing (2 nurses participated in both phases). Analysis of the qualitative data revealed four themes for the interface design to be (1) clear and consistent, (2) vigilant, (3) interoperable, and (4) reliable. The major elements of the final prototype included a feature for viewing the predicted and actual blood pressure over time to determine the reliability of the predictions, a drop-down option to report patient side effects, a feature to report reasons for not accepting the prediction, and a visual alert indicating any systolic blood pressure predictions below 90 mm Hg. Nurses' ratings on the questionnaires indicated excellent usability and acceptability of the final nitro DSS prototype. CONCLUSION: This study successfully applied a UCD approach to collaborate with nurses in developing a user interface for the nitro DSS that supports the clinical decision-making of nurses titrating nitroglycerin.

Asunto(s)

Sistemas de Apoyo a Decisiones Clínicas , Nitroglicerina , Interfaz Usuario-Computador , Nitroglicerina/administración & dosificación , Nitroglicerina/uso terapéutico , Humanos , Relación Dosis-Respuesta a Droga

RESUMEN

OBJECTIVE: To describe the clinical course and treatment of 3 dogs with peripheral vasopressor extravasation. CASE SERIES SUMMARY: Although vasopressor extravasation (VE) is a well-documented complication in human medicine, literature describing VE and its management in veterinary patients is sparse. VE increases patient morbidity by causing local tissue injury and necrosis. The gold standard treatment for VE, phentolamine, has been periodically limited in supply in human medicine and is not consistently available for use in veterinary medicine. An alternative protocol proposed for use in people with VE combines topical nitroglycerin application with subcutaneous terbutaline infiltration. In this report, a treatment protocol utilizing these therapies was used to treat 3 dogs with VE and secondary tissue injury. NEW OR UNIQUE INFORMATION PROVIDED: This report describes 3 cases of VE-induced tissue injury in dogs. In addition, this report describes the use of perivascular terbutaline infiltration and topical nitroglycerin application as therapeutic management for VE in dogs.

Asunto(s)

Administración Tópica , Enfermedades de los Perros , Nitroglicerina , Terbutalina , Animales , Perros , Nitroglicerina/administración & dosificación , Nitroglicerina/uso terapéutico , Terbutalina/administración & dosificación , Terbutalina/uso terapéutico , Enfermedades de los Perros/tratamiento farmacológico , Masculino , Femenino , Extravasación de Materiales Terapéuticos y Diagnósticos/veterinaria , Extravasación de Materiales Terapéuticos y Diagnósticos/tratamiento farmacológico , Inyecciones Subcutáneas/veterinaria , Vasoconstrictores/administración & dosificación , Vasoconstrictores/uso terapéutico , Pomadas , Vasodilatadores/administración & dosificación , Vasodilatadores/uso terapéutico

RESUMEN

OBJECTIVE: Our aim was to survey astrocyte and microglial activation across four brain regions in a mouse model of chronic migraine. BACKGROUND: Chronic migraine is a leading cause of disability, with higher rates in females. The role of central nervous system neurons and glia in migraine pathophysiology is not fully elucidated. Preclinical studies have shown abnormal glial activation in the trigeminal nucleus caudalis of male rodents. No current reports have investigated glial activation in both sexes in other important brain regions involved with the nociceptive and emotional processing of pain. METHODS: The mouse nitroglycerin model of migraine was used, and nitroglycerin (10 mg/kg) or vehicle was administered every other day for 9 days. Prior to injections on days 1, 5, and 9, cephalic allodynia was determined by periorbital von Frey hair testing. Immunofluorescent staining of astrocyte marker, glial fibrillary protein (GFAP), and microglial marker, ionized calcium binding adaptor molecule 1 (Iba1), in male and female trigeminal nucleus caudalis, periaqueductal gray, somatosensory cortex, and nucleus accumbens was completed. RESULTS: Behavioral testing demonstrated increased cephalic allodynia in nitroglycerin- versus vehicle-treated mice. An increase in the percent area covered by GFAP+ cells in the trigeminal nucleus caudalis and nucleus accumbens, but not the periaqueductal gray or somatosensory cortex, was observed in response to nitroglycerin. No significant differences were observed for Iba1 staining across brain regions. We did not detect significant sex differences in GFAP or Iba1 quantification. CONCLUSIONS: Immunohistochemical analysis suggests that, at the time point tested, immunoreactivity of GFAP+ astrocytes, but not Iba1+ microglia, changes in response to chronic migraine-associated pain. Additionally, there do not appear to be significant differences between males and females in GFAP+ or Iba1+ cells across the four brain regions analyzed.

Asunto(s)

Modelos Animales de Enfermedad , Trastornos Migrañosos , Nitroglicerina , Animales , Nitroglicerina/farmacología , Trastornos Migrañosos/metabolismo , Trastornos Migrañosos/fisiopatología , Masculino , Femenino , Ratones , Hiperalgesia/fisiopatología , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/metabolismo , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Ratones Endogámicos C57BL , Corteza Somatosensorial/efectos de los fármacos , Corteza Somatosensorial/fisiopatología , Neuroglía/efectos de los fármacos , Neuroglía/metabolismo , Proteínas de Unión al Calcio/metabolismo , Sustancia Gris Periacueductal/efectos de los fármacos , Sustancia Gris Periacueductal/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Emociones/fisiología , Emociones/efectos de los fármacos , Proteínas de Microfilamentos/metabolismo , Vasodilatadores/farmacología , Enfermedad Crónica , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Núcleo Caudal del Trigémino/efectos de los fármacos , Núcleo Caudal del Trigémino/metabolismo

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Paeonol (PAE) and glycyrrhizic acid (GLY) are predominate components of 14 blood-entering ones of Piantongtang No. 1, which is a traditional Chinese medicine prescription for chronic migraine with minimal side effects. Both paeonol and glycyrrhizic acid exhibit analgesic, neuroprotective and anti-inflammatory properties individually. Our previous research has highlighted their combined effect (PAE + GLY) in ameliorating migraine symptoms. However, there are not yet any studies exploring the mechanism of action of PAE + GLY in the treatment of migraine. AIM OF THE STUDY: This research aimed to determine the mechanism of PAE + GLY in ameliorating the recurrent nitroglycerin-induced migraine-like phenotype in rats. MATERIALS AND METHODS: Using a nitroglycerin-induced migraine model via subcutaneous injection in the neck, we evaluated the effect of PAE + GLY on migraine-like symptoms. Behavioural tests and biomarkers analysis were employed, alongside transcriptome sequencing (RNA-seq). Mechanistic insights were further verified utilising reverse transcription quantitative PCR (RT-qPCR), Western blot (WB), ELISA and immunofluorescence (IF) techniques. RESULTS: Following treatment with PAE + GLY, hyperalgesia threshold and 5-hydroxytryptamine (5-HT) levels increased, and migraine-like head scratching, histamine and calcitonin gene-related peptide (CGRP) levels were reduced. RNA-Seq experiments revealed that PAE + GLY upregulated the expression of Glutamate decarboxylase 2 (GAD2) and γ-aminobutyric acid type B receptor subunit 2 (GABBR2) genes. This upregulation activated the GABAergic synapse pathway, effectively inhibiting migraine attacks. Further validation demonstrated an increase in γ-aminobutyric acid (GABA) content in cerebrospinal fluid post PAE + GLY treatment, coupled with increased expression of dural GAD2, GABBR2 and transient receptor potential channel M8 (TRPM8). Consequently, this inhibited the expression of dural cAMP-dependent protein kinase catalytic subunit alpha (PRKACA) and transient receptor potential channel type 1 (TRPV1), subsequently downregulating p-ERK1/2, p-AKT1, IL-1ß and TNF-α. CONCLUSIONS: Our findings underscore that PAE + GLY ameliorates inflammatory hyperalgesia migraine by upregulating inhibitory neurotransmitters and modulating the GABBR2/TRPM8/PRKACA/TRPV1 pathway.

Asunto(s)

Acetofenonas , Ácido Glicirrínico , Trastornos Migrañosos , Nitroglicerina , Canales Catiónicos TRPM , Canales Catiónicos TRPV , Animales , Masculino , Ratas , Acetofenonas/farmacología , Modelos Animales de Enfermedad , Quimioterapia Combinada , Ácido Glicirrínico/farmacología , Ácido Glicirrínico/uso terapéutico , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/inducido químicamente , Trastornos Migrañosos/metabolismo , Nitroglicerina/toxicidad , Nitroglicerina/farmacología , Fenotipo , Proteína Quinasa C-alfa/metabolismo , Proteína Quinasa C-alfa/genética , Ratas Sprague-Dawley , Receptores de GABA/metabolismo , Receptores de GABA/genética , Transducción de Señal/efectos de los fármacos , Canales Catiónicos TRPM/metabolismo , Canales Catiónicos TRPM/genética , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genética

RESUMEN

BACKGROUND: This study aimed to investigate the effectiveness of combining sevoflurane with remifentanil, esmolol, or nitroglycerin for hypotensive anesthesia and determine the suitable hypotensive anesthesia method for orthognathic surgery. MATERIAL AND METHODS: This retrospective study included 60 patients who underwent orthognathic surgery for developmental malocclusion. They were divided into three groups based on the hypotensive agent preferences: Group 1 (n = 20), sevoflurane and remifentanil; Group 2 (n = 20), sevoflurane and esmolol; Group 3 (n = 20), sevoflurane and nitroglycerin. Bleeding volume, heart rate, systolic, diastolic, and mean arterial blood pressure were recorded at certain times during the perioperative period, including at stages with increased stress levels in the body, such as incision and osteotomy. The patients' blood pressure, analgesic consumption and pain level were recorded in the postoperative period. RESULTS: Bleeding volume, surgery satisfaction related to bleeding, and total operation time did not differ significantly between groups. Intraoperatively, heart rates were significantly higher in Group 3 than in Groups 1 and 2 (p = 0.001). However, hemodynamic stability was similar in Groups 1 and 2. Postoperatively, analgesic consumption, pain levels, and blood pressure dynamics did not differ significantly between groups (p > 0.05). CONCLUSIONS: Based on this study's results, it was concluded that infusing remifentanil, esmolol, or nitroglycerin with sevoflurane during orthognathic surgery successfully achieved the targeted hypotensive anesthesia and can be considered alternative methods. The decision on which method to use should consider the patient's overall health status and additional medical conditions.

Asunto(s)

Procedimientos Quirúrgicos Ortognáticos , Remifentanilo , Sevoflurano , Humanos , Estudios Retrospectivos , Sevoflurano/administración & dosificación , Femenino , Masculino , Remifentanilo/administración & dosificación , Procedimientos Quirúrgicos Ortognáticos/métodos , Adulto , Adulto Joven , Nitroglicerina/administración & dosificación , Propanolaminas/administración & dosificación , Propanolaminas/uso terapéutico , Hipotensión Controlada/métodos , Piperidinas/administración & dosificación , Éteres Metílicos/administración & dosificación , Adolescente , Anestésicos por Inhalación/administración & dosificación

RESUMEN

INTRODUCTION: The development of several experimental migraine provocation models has significantly contributed to an understanding of the signaling mechanisms of migraine. The early history of this development and a view to the future are presented as viewed by the inventor of the models. METHODS: Extensive knowledge of the literature was supplemented by scrutiny of reference lists. RESULTS: Early studies used methodologies that were not blinded. They suggested that histamine and nitroglycerin (Glyceryl trinitrate, GTN) could induce headache and perhaps migraine. The development of a double blind, placebo-controlled model, and the use of explicit diagnostic criteria for induced migraine was a major step forward. GTN, donor of nitric oxide (NO), induced headache in people with- and without migraine as well as delayed migraine attacks in those with migraine. Calcitonin gene-related peptide (CGRP) did the same, supporting the development of CGRP antagonists now widely used in patients. Likewise, pituitary adenylate cyclase activating peptide (PACAP) provoked headache and migraine. Recently a PACAP antibody has shown anti migraine activity in a phase 2 trial. Increase of second messengers activated by NO, CGRP and PACAP effectively induced migraine. The experimental models have also been used in other types of headaches and have been combined with imaging and biochemical studies. They have also been used for drug testing and in genetic studies. CONCLUSION: Conclusion. Human migraine provocation models have informed about signaling mechanisms of migraine leading to new drugs and drug targets. Future use of these models in imaging-, biochemistry- and genetic studies as well as in the further study of animal models is promising.

Asunto(s)

Trastornos Migrañosos , Transducción de Señal , Trastornos Migrañosos/tratamiento farmacológico , Humanos , Animales , Transducción de Señal/efectos de los fármacos , Péptido Relacionado con Gen de Calcitonina/antagonistas & inhibidores , Péptido Relacionado con Gen de Calcitonina/metabolismo , Nitroglicerina/farmacología , Modelos Animales de Enfermedad