Gastrodin alleviates NTG-induced migraine-like pain via inhibiting succinate/HIF-1α/TRPM2 signaling pathway in trigeminal ganglion.

BACKGROUND: Increasing evidence highlights the involvement of metabolic disorder and calcium influx mediated by transient receptor potential channels in migraine; however, the relationship between these factors in the pathophysiology of migraine remains unknown. Gastrodin is the major component of the traditional Chinese medicine Tianma, which is extensively used in migraine therapy. PURPOSE: Our work aimed to explore the analgesic action of gastrodin and its regulatory mechanisms from a metabolic perspective. METHODS/RESULTS: After being treated with gastrodin, the mice were given nitroglycerin (NTG) to induce migraine. Gastrodin treatment significantly raised the threshold of sensitivity in response to both mechanical and thermal stimulus evidenced by von Frey and hot plate tests, respectively, and decreased total contact numbers in orofacial operant behavioral assessment. We found that the expression of transient receptor potential melastatin 2 (TRPM2) channel was increased in the trigeminal ganglion (TG) of NTG-induced mice, resulting in a sustained Ca2+ influx to trigger migraine pain. The content of succinate, a metabolic biomarker, was elevated in blood samples of migraineurs, as well as in the serum and TG tissue from NTG-induced migraine mice. Calcium imaging assay indicated that succinate insult elevated TRPM2-mediated calcium flux signal in TG neurons. Mechanistically, accumulated succinate upregulated hypoxia inducible factor-1α (HIF-1α) expression and promoted its translocation into nucleus, where HIF-1α enhanced TRPM2 expression through transcriptional induction in TG neurons, evidenced by luciferase reporter measurement. Gastrodin treatment inhibited TRPM2 expression and TRPM2-dependent Ca2+ influx by attenuating succinate accumulation and downstream HIF-1α signaling, and thereby exhibited analgesic effect. CONCLUSION: This work revealed that succinate was a critical metabolic signaling molecule and the key mediator of migraine pain through triggering TRPM2-mediated calcium overload. Gastrodin alleviated NTG-induced migraine-like pain via inhibiting succinate/HIF-1α/TRPM2 signaling pathway in TG neurons. These findings uncovered the anti-migraine effect of gastrodin and its regulatory mechanisms from a metabolic perspective and provided a novel theoretical basis for the analgesic action of gastrodin.

Comparing the Effects of Sesame Oil vs. Nitroglycerin Ointment on the Incidence of Chemotherapy-Induced Phlebitis: A Single Blind Clinical Trial.

BACKGROUND: Phlebitis is a severe inflammatory response in patients undergoing chemotherapy that can lead to complications and increased length of hospitalization. OBJECTIVE: This study was conducted to examine the effects of sesame oil and nitroglycerin ointment on the incidence of chemotherapy-induced phlebitis in patients with cancer.  Methods: This clinical trial study involved 138 cancer patients who were randomly assigned into three groups. The three groups received nitroglycerin ointment, sesame oil, or betadine alcoholic solution that were applied on the distal catheter area at a length of 1.5 centimeters and width of 2 × 4 cm using graded paper. The site was then dressed and fixed with anti-allergenic adhesives. The research samples were examined for 72 hours for the incidence of phlebitis. RESULTS: No statistically significant difference was observed between the incidence of phlebitis in the sesame oil, nitroglycerin ointment and alcohol-betadine groups in the first 24 hours (p=0.2), the second 24 hours (p=0.13) and the third 24 hours (p=0.13). CONCLUSION: External use of both sesame oil and nitroglycerin is effective in reducing chemotherapy-induced phlebitis. Due to its anti-inflammatory effect and low cost, however, using sesame oil is recommended.

Supplementation with SCFAs Re-Establishes Microbiota Composition and Attenuates Hyperalgesia and Pain in a Mouse Model of NTG-Induced Migraine.

Migraine is a common brain-disorder that affects 15% of the population. Converging evidence shows that migraine is associated with gastrointestinal disorders. However, the mechanisms underlying the interaction between the gut and brain in patients with migraine are not clear. In this study, we evaluated the role of the short-chain fatty acids (SCFAs) as sodium propionate (SP) and sodium butyrate (SB) on microbiota profile and intestinal permeability in a mouse model of migraine induced by nitroglycerine (NTG). The mice were orally administered SB and SP at the dose of 10, 30 and 100 mg/kg, 5 min after NTG intraperitoneal injections. Behavioral tests were used to evaluate migraine-like pain. Histological and molecular analyses were performed on the intestine. The composition of the intestinal microbiota was extracted from frozen fecal samples and sequenced with an Illumina MiSeq System. Our results demonstrated that the SP and SB treatments attenuated hyperalgesia and pain following NTG injection. Moreover, SP and SB reduced histological damage in the intestine and restored intestinal permeability and the intestinal microbiota profile. These results provide corroborating evidence that SB and SP exert a protective effect on central sensitization induced by NTG through a modulation of intestinal microbiota, suggesting the potential application of SCFAs as novel supportive therapies for intestinal disfunction associated with migraine.

A comparative study of transdermal nitroglycerine patch and oral nifedipine in preterm labor.

Background: Currently, the main goal for the use of tocolytic therapy is to delay the birth so as to allow the use of corticosteroids for accelerating fetal lung maturity and maternal transfer to a tertiary care center and thereby reducing neonatal morbidity and mortality. Aims and Objectives: The aims amd objectives were to compare the safety and efficacy of transdermal nitroglycerine patch with oral nifedipine as a tocolytic agent to arrest preterm labor and prevent preterm birth. Materials and Methods: Based on the selection criteria, 50 patients were selected randomly in Group A and Group B. Group A women were given transdermal nitroglycerin patch, which delivered 10 mg Nitroglycerin (NTG) over 24 h and it was applied to the woman's abdomen followed by another patch of 10 mg after 1 h if contractions persisted. After 24 h, it was replaced by a fresh patch. Group B women were given an oral loading dose of nifedipine 20 mg followed by a similar dose if contractions persisted after 1 h. A maintenance dose of 10 mg thrice daily was given if contractions were suppressed. Patients were monitored from the time of admission to the time of discharge. Results: The mean duration of prolongation of pregnancy in Group B (3.68 ± 1.91 days) was significantly more than Group A (2.78 ± 1.39 days). Headache was seen significantly more in Group A (42%) than group B (6%). Tachycardia, hypotension, and palpitation showed no statistically significant difference between them. There was no statistically significant difference in the birth weight of the babies in both the groups. Conclusion: Nifedipine is a safe and effective drug in prolonging preterm labor and has minimal maternal and neonatal side effects.

RésuméContexte: Actuellement, le principal objectif de l'utilisation de la thérapie tocolytique est de retarder la naissance afin de permettre l'utilisation de corticostéroïdes pour accélérer la maturité pulmonaire fœtale et le transfert maternel vers un centre de soins tertiaires et ainsi réduire la morbidité et la mortalité néonatales. Buts et objectifs: Les buts et objectifs étaient de comparer l'innocuité et l'efficacité du timbre transdermique de nitroglycérine avec la nifédipine par voie orale comme agent tocolytique pour arrêter le travail prématuré et prévenir l'accouchement prématuré. Matériel et méthodes: Sur la base des critères de sélection, 50 patientes ont été sélectionnées au hasard dans les groupes A et B.Les femmes du groupe A ont reçu un patch transdermique de nitroglycérine, qui a administré 10 mg de NTG en 24 h et appliqué sur l'abdomen de la femme suivi d'un autre patch de 10 mg après 1 h si les contractions ont persisté. Après 24 h, il a été remplacé par un nouveau patch. Les femmes du groupe B ont reçu une dose de charge orale de 20 mg de nifédipine suivie d'une dose similaire si les contractions persistaient après 1 h. Une dose d'entretien de 10 mg trois fois par jour était administrée si les contractions étaient supprimées. Les patients ont été suivis du moment de l'admission au moment de la sortie. Résultats: La durée moyenne de prolongation de la grossesse dans le groupe B (3,68 ± 1,91 jours) était significativement plus élevée que dans le groupe A (2,78 ± 1,39 jours). Les céphalées étaient significativement plus observées dans le groupe A (42%) que dans le groupe B (6%). La tachycardie, l'hypotension et les palpitations n'ont montré aucune différence statistiquement significative entre elles. Il n'y avait pas de différence statistiquement significative du poids à la naissance des bébés dans les deux groupes. Conclusion: La nifédipine est un médicament sûr et efficace pour prolonger le travail prématuré et a des effets secondaires maternels et néonatals minimes.

Nicardipine: When high dose nitrates fail in treating heart failure.

Sympathetic Crashing Acute Pulmonary Edema (SCAPE) describes patients who present with acute hypertensive cardiogenic pulmonary edema. These patients present in respiratory distress, and requiring immediate medical and airway management. The treatment of SCAPE includes non-invasive positive pressure ventilation (NIPPV) to maintain oxygenation, and high dose nitrates to lower blood pressure and reduce afterload. We present a case report of a patient with refractory hypertension to high dose nitrates likely due to nitroglycerin resistance or an attenuated response. The addition of nicardipine led to marked clinical improvement, normalized blood pressure and spared the patient from endotracheal intubation and admission to the intensive care unit.

Effect of applying reflexology massage on nitroglycerin-induced migraine-type headache: A placebo-controlled clinical trial.

OBJECTIVES: Nitroglycerin (NTG)-induced migraine-type headache is the most prominent side effect of nitrate therapy. Therefore, the aim of this study was to clarify the effectiveness of reflexology massage on intravenous NTG-induced headache in coronary care unit (CCU) inpatients. METHODS: This was a randomized clinical trial. The study sample included 75 patients that were randomly divided into three groups: control, intervention, and placebo groups. The intensity of baseline headache in patients who received NTG was measured by the numeric rating scale for pain (NRS Pain). Patients in the intervention group received reflexology massage two times for 20 min (at 3-h interval), wherein the upper part of patient's both foot thumbs, which is the reflection point of the head, was massaged. In the placebo group, an unspecified point on the foot (heel), which was not related to the head, was massaged. Patients in the control group did not receive any massage. RESULTS: No baseline differences existed among the three groups for the mean pain scale score (p=0.66) before the study; but the difference between the groups after the application was statistically significant (p=0.000). CONCLUSION: Reflexology massage can reduce the intensity of NTG-induced headache.

Metabolomics Strategy Using High Resolution Mass Spectrometry Reveals Novel Biomarkers and Pain-Relief Effect of Traditional Chinese Medicine Prescription Wu-Zhu-Yu Decoction Acting on Headache Modelling Rats.

Headache is a common episodic or chronic neurologic disorder. Treatment options and diagnosis are restricted by an incomplete understanding of disease pathology and the lack of diagnostic markers. Wu-Zhu-Yu decoction (WZYD), a traditional Chinese medicine (TCM) formula containing four TCM herbs, is commonly used in the treatment of headache in China. To deeply understand more about headache and investigate the pain-relief mechanism of WZYD, a comprehensive metabolomics study combined with multivariate data processing strategy was carried out. An LC-high resolution mass spectrometry-based metabolomics approach was applied to characterize metabolic biomarker candidates. Multiple pattern recognition including principal component analysis-discriminant analysis, partial least squares-discriminant analysis and hierarchical cluster analysis were used to determine groups and confirm important variables. A total of 17 potential biomarkers were characterized and related metabolic pathways were identified. The study demonstrated that the established metabolomics strategy is a powerful approach for investigating the mechanism of headache attack and WZYD. In addition, the approach may highlight biomarkers and metabolic pathways and can capture subtle metabolite changes from headache, which may lead to an improved mechanism understanding of central nervous system diseases and TCM treatment.

Baicalin Alleviates Nitroglycerin-induced Migraine in Rats via the Trigeminovascular System.

Migraine is a common neurological disorder with a serious impact on quality of life. The aim of this study was to explore the effect of baicalin on nitroglycerin-induced migraine rats. We carried out a behavioral research within 2 h post-nitroglycerin injection, and blood samples were drawn for measurements of nitric oxide (NO), calcitonin gene-related peptide, and endothelin (ET) levels. Immunohistochemistry was adopted to detect the activation of C-fos immunoreactive neurons in periaqueductal gray. The number, area size, and integrated optical density of C-fos positive cells were measured using Image-Pro Plus. As a result, baicalin administration (0.22 mm/kg) alleviated pain responses of migraine rats. It profoundly decreased NO and calcitonin gene-related peptide levels, increased ET levels, and rebuilt the NO/ET balance in migraine rats. Besides, baicalin pretreatment significantly reduced the number, the stained area size, and integrated optical density value of C-fos positive cells. In brief, this paper supports the possibility of baicalin as a potential migraine pharmacotherapy. Copyright © 2017 John Wiley & Sons, Ltd.

Pharmacological characterization of a novel gastrodin derivative as a potential anti-migraine agent.

Migraine is a highly prevalent neurovascular disorder in the brain. An optimal therapy for migraine has not yet been developed. Gastrodin (Gas), the main effective constitute from Gastrodiae Rhizoma (Tianma in Chinese), has been indicated for migraine treatment and prophylaxis more than 30 years, with demonstrated safety. However, Gas is a phenolic glycoside, with relatively low concentrations and weak efficacy in the central nervous system. To develop more effective anti-migraine agents, we synthesized a novel Gas derivative (Gas-D). In the present study, comparative pharmacodynamic evaluations of Gas and Gas-D were performed in a model of nitroglycerin (NTG)-induced migraine in rats and the hot-plate test in mice. Following behavioral testing in this migraine model, external jugular vein blood and the trigeminal nucleus caudalis (TNC) were collected to analyze plasma nitric oxide (NO) and calcitonin gene-related peptide (CGRP) concentrations and c-Fos expression in the TNC. The acute oral toxicity of Gas and Gas-D was also examined. We found that Gas-D had potent anti-migraine effects, likely attributable to inhibition of both trigeminal nerve activation at central sites and the peripheral release of CGRP following NO scavenging. Additionally, Gas-D exerted significant anti-nociceptive effect in response to thermal pain compared with Gas. Furthermore, a single dose of 2.048 g/kg Gas or Gas-D presented no acute oral toxicity in mice. Altogether, the potent anti-migraine and anti-hyperalgesic effects of Gas-D suggest that it might be a potentially novel drug candidate for migraine treatment or prophylaxis.

Daily low-dose folic acid supplementation does not prevent nitroglycerin-induced nitric oxide synthase dysfunction and tolerance: a human in vivo study.

INTRODUCTION: Continuous treatment with nitroglycerin (GTN) causes tolerance and endothelial dysfunction, both of which may involve endothelial nitric oxide synthase (eNOS) dysfunction. eNOS dysfunction may be linked to depletion of tetrahydrobiopterin, and folic acid may be involved in the regeneration of this cofactor. It has been demonstrated that 10 mg/day folic acid supplementation prevents the development of GTN tolerance and GTN-induced endothelial dysfunction. However, the efficacy of daily lower-dose folic acid supplementation for preventing these phenomena has not been investigated. OBJECTIVE: To determine the effect of 1 mg/day folic acid supplementation on responses to sustained GTN therapy. METHODS AND RESULTS: On visit 1, 20 healthy male volunteers were randomly assigned to receive either oral folic acid (1 mg/day) or placebo for one week in a double- blind study. All subjects also received continuous transdermal GTN (0.6 mg/h). On visit 2, forearm blood flow was measured using venous occlusion strain-gauge plethysmography in response to incremental intra-arterial infusions of acetylcholine, N-monomethyl-L-arginine and GTN. Subjects in both groups displayed significantly decreased responses to acetylcholine and N-monomethyl-L-arginine infusions compared with a control group that received no treatment. Responses to GTN were also significantly diminished in both groups (P<0.05 for all). DISCUSSION: The present data demonstrate that daily supplementation with 1 mg folic acid does not prevent the development of GTN-induced eNOS dysfunction or tolerance.

Nitrate tolerance as a possible cause of multidrug-resistant coronary artery spasm.

Coronary spasm can usually be controlled by administration of Ca antagonists. However, there are some cases of coronary spasm whose attacks cannot be controlled even with large doses of Ca antagonist and/or its combination with nitrates. Here we describe the case of a 41-year-old man whose attacks of coronary spasm were resistant to the combined administration of nitrates, Ca antagonists, and a statin. The attacks were alleviated and disappeared after withdrawal of nitrates and recurred after readministration of a nitroglycerin patch. The involvement of nitrate tolerance in the pathogenesis of multidrug resistant coronary spasm was revealed and its implication discussed.

Transdermal nitroglycerin therapy may not prevent early postmenopausal bone loss.

CONTEXT: Osteoporosis is common among postmenopausal women; animal studies and human pilot studies support the concept of nitric oxide (NO) donors reducing bone mineral density loss. OBJECTIVE: The objective of the study was to evaluate whether NO donor, nitroglycerin, prevents postmenopausal bone loss. DESIGN: This was a 3-yr randomized, double blinded, single-center, placebo-controlled clinical trial. SETTING: The single-center study was conducted at the University of Medicine and Dentistry-Robert Wood Johnson Medical School (New Brunswick, NJ). PARTICIPANTS: Participants included 186 postmenopausal women aged 40-65 yr, with lumbar bone mineral density (BMD) T-scores of 0 to -2.5. INTERVENTION: Women, stratified by lumbar T-score (<-1.50 and >or=-1.50) and years since menopause (5 yr), were randomized to receive nitroglycerin ointment (22.5 mg as Nitro-Bid) or placebo ointment received daily for 3 yr. Both groups took 630 mg daily calcium plus 400 IU vitamin D supplements. MEASUREMENTS: BMD was measured at 6 months and annually by dual-energy x-ray absorptiometry. Percent change in lumbar vertebrae BMD was the primary outcome. Hip BMD, total body bone mineral content, and height were secondary outcomes. RESULTS: After 36 months of therapy, changes of -2.1% in the active group (n = 88) and -2.5% in the placebo group (n = 82) in lumbar spine BMD were seen (P = 0.59; 95% confidence interval -1.001, 1.975). Secondary outcomes also did not differ by intervention arm. The active group reported more headaches compared with the placebo group (57 vs. 14%, P < 0.001). Other adverse and serious adverse events were not different. CONCLUSIONS: BMD changes did not substantially differ between postmenopausal women who received the dose of nitroglycerin tested, in comparison with a placebo. Once-daily dosing with 22.5 mg of transdermal-administered nitroglycerin was not effective (compliance adjusted dose was only approximately 16 mg/d); a sub-therapeutic dose.

Efficacy of nitroglycerine infusion versus sublingual nifedipine in severe pre-eclampsia: a randomized, triple-blind, controlled trial.

1. Information regarding the use of continuous i.v. administration of nitroglycerine as an antihypertensive agent in the management of pre-eclampsia is scarce. In the present study, i.v. nitroglycerine or sublingual nifedipine were administered to 32 women with severe pre-eclampsia who were being managed with controlled plasma volume expansion and MgSO(4) loading and maintenance doses. Maternal blood pressure and heart rate responses, fetal heart rate responses and perinatal fetal-maternal adverse effects were evaluated using classical parametric and non-parametric data analysis and data modelling by mixed models. 2. An important hypotensive response was observed in both groups, although this reponse was greater, faster and exhibited less variability (more precision) in the nitroglycerine-treated group. Heart rate also increased in both the nitroglycerine- and nifedipine-treated groups (4.6 +/- 4.4 vs 8.6 +/- 5.3 b.p.m., respectively), although the increase in the nifedipine-treated group was almost twofold that in the nitroglycerine-treated group. There were no significant changes in fetal heart rate in response to vasodilator therapy. The frequency of perinatal fetal-maternal adverse effects was similar in both groups at 40% and the adverse effects observed included flushing, headache, palpitations and nausea. 3. In conclusion, i.v. infusion of nitroglycerine is an effective, safe and alternative therapy for severe pre-eclampsia.

Pharmacological advancements in the treatment of chronic anal fissure.

Chronic anal fissure is a tear in the lining of the anal canal that, if not treated appropriately at an early stage, causes considerable anal pain during defaecation. Surgery is no longer considered the first-line treatment of this common condition, as recent advancements in medical treatment has produced promising results in the healing of fissures, thus avoiding the unwanted complications that frequently occur following operative treatment. This review looks at those pharmacological agents used commonly in the treatment of chronic anal fissures and explores alternative therapies that may be of benefit in the future.

Hypothalamic stimulation in chronic cluster headache: a pilot study of efficacy and mode of action.

We enrolled six patients suffering from refractory chronic cluster headache in a pilot trial of neurostimulation of the ipsilateral ventroposterior hypothalamus using the stereotactic coordinates published previously. After the varying durations needed to determine optimal stimulation parameters and a mean follow-up of 14.5 months, the clinical outcome is excellent in three patients (two are pain-free; one has fewer than three attacks per month), but unsatisfactory in one patient, who only has had transient remissions. Mean voltage is 3.28 V, diplopia being the major factor limiting its increase. When the stimulator was switched off in one pain-free patient, attacks resumed after 3 months until it was turned on again. In one patient the implantation procedure had to be interrupted because of a panic attack with autonomic disturbances. Another patient died from an intracerebral haemorrhage that developed along the lead tract several hours after surgery; there were no other vascular changes on post-mortem examination. After 1 month, the hypothalamic stimulation induced resistance against the attack-triggering agent nitroglycerin and tended to increase pain thresholds at extracephalic, but not at cephalic, sites. It had no detectable effect on neurohypophyseal hormones or melatonin excretion. We conclude that hypothalamic stimulation has remarkable efficacy in most, but not all, patients with treatment-resistant chronic cluster headache. Its efficacy is not due to a simple analgesic effect or to hormonal changes. Intracerebral haemorrhage cannot be neglected in the risk evaluation of the procedure. Whether it might be more prevalent than in deep-brain stimulation for movement disorders remains to be determined.

Adverse effects of nitroglycerin treatment on endothelial function, vascular nitrotyrosine levels and cGMP-dependent protein kinase activity in hyperlipidemic Watanabe rabbits.

OBJECTIVE: With the present studies we sought to determine how treatment with nitroglycerin (NTG) affects endothelial function, oxidative stress and nitric oxide (NO)-downstream signaling in Watanabe heritable hyperlipidemic rabbits (WHHL). BACKGROUND: In vitro experiments have demonstrated potent antiatherosclerotic effects of NO suggesting that treatment with NO-donors such as NTG could compensate for the diminished availability of endothelial NO. Nitric oxide may, however, not only be scavenged by reaction with endothelium-derived superoxide but also form the potent oxidant and inhibitor of vascular function, peroxynitrite (ONOO(-)). METHODS: Watanabe heritable hyperlipidemic rabbits were treated for three days with NTG patches. Normolipidemic New Zealand White rabbits (NZWR) served as controls. Endothelial function was assessed ex vivo with organ chamber experiments and vascular superoxide was quantified using lucigenin (5 and 250 microM) and CLA-enhanced chemiluminescence. Vascular ONOO(-) formation was determined using nitrotyrosine antibodies. The activity of the cGMP-dependent kinase (cGK-I) was assessed by determining the phosphorylation of vasodilator-stimulated phosphoprotein VASP (P-VASP). RESULTS: Nitroglycerin treatment caused endothelial dysfunction in NZWR and WHHL, associated with an increase in superoxide and ONOO(-) production and a substantial drop in cGK-I activity. In vivo NTG-treatment decreased lipophilic antioxidants (alpha- and beta-carotene) in NZWR and WHHL. Treatment of NZWR with NTG also decreased plasma extracellular superoxide dismutase (EC-SOD)-activity. CONCLUSIONS: Nitroglycerin treatment of WHHL with exogenous NO worsens rather than improves endothelial dysfunction secondary to increased formation of superoxide and/or peroxynitrite leading to decreased cGK-I activity. The decrease in plasma levels of alpha- and beta-carotene may be at least in part due to a decrease in EC-SOD activity.

Double blind randomised controlled trial of topical glyceryl trinitrate in anal fissure.

AIMS: To determine the effectiveness and safety of topical glyceryl trinitrate (GTN) in the management of acute anal fissure in children. METHODS: Individual children were randomised to receive GTN paste or placebo for six weeks in addition to oral senna and lactulose. Patients took laxatives alone for a further 10 weeks. Each week a research nurse telephoned families to assess pain scores and give advice. Main outcome measures were validated standardised pain scores and time to painless defaecation. RESULTS: Forty subjects were recruited from 46 eligible children; 31 children completed the trial (13 in the GTN group and 18 in the placebo group). No differences in the proportion of those achieving pain free defaecation with relation to time were seen between the two groups. Similarly, there were no significant differences in pain scores between the two groups over the 16 week study period. However, in both groups pain scores had decreased significantly. There were no differences in the incidence of rectal bleeding, faecal soiling, presence of visible fissure, skin tag, or faecal loading at outpatient review at the time of recruitment, or at 6 weeks and 16 weeks. No serious adverse effects were observed. CONCLUSIONS: This study suggests that 0.2% GTN paste is ineffective in the treatment of acute anal fissures in childhood. However the overall fissure healing rate is high (84%) with associated reduction in pain scores, suggesting that a nurse based treatment programme can achieve a high rate of fissure healing.

[Salvia Miltiorrhizae Composita in preventing PaO2 lowering induced by controlled hypotension with nitroglycerin].

OBJECTIVE: To observe the effects of Salvia Miltiorrhizae Composita (SMC) on blood gas variations of nitroglycerin (NTG) controlled hypotension. METHODS: Sixteen patients who were arranged to undergo operation under general anesthesia in controlled hypotension condition were divided randomly into control group (n = 8) and SMC group (treated group, n = 8), NTG were used to create controlled hypotension in both groups and blood pressure decrease about 30% comparing with the control values. Patients in the treated group were administered intravenously with SMC (16 ml) before the utilization of NTG. RESULTS: Significant PaO2 decrease and Pa-etCO2 increase were observed in the control group during the controlled hypotension period. However, blood gas values in the treated group did not evidently change. CONCLUSION: It suggested that SMC can prevent the side effects of NTG on blood gas.

Abnormal rheologic effects of glyceryl trinitrate in patients with non-insulin-dependent diabetes mellitus and reversal by antioxidants.

OBJECTIVE: To evaluate 1) the hemorrheologic and hemodynamic effects of glyceryl trinitrate in patients with non-insulin-dependent diabetes mellitus and 2) the influence of antioxidants on these effects. DESIGN: Case-control study. SETTING: University hospital clinic. PATIENTS: 40 patients with diabetes and no evidence of cardiovascular complications and 40 controls matched for demographic variables and body habitus. INTERVENTIONS: Sublingual glyceryl trinitrate (0.3 mg) and transdermal glyceryl trinitrate patches (10 mg/d). Vitamin E, 300 mg/d orally for 7 days, and glutathione, 600 mg intravenously or intramuscularly, were given to test the effects of antioxidant supplementation. MEASUREMENTS: Systolic, diastolic, and mean arterial pressure and heart rate; left ventricular ejection fraction; platelet aggregation, blood viscosity, and blood filterability in vitro and ex vivo. RESULTS: Compared with controls, patients with diabetes had increased platelet aggregation to adenosine diphosphate (P < 0.005), increased blood viscosity (P < 0.001), and decreased blood filterability (P = 0.041) at baseline; blood pressure, heart rate, and ejection fraction were similar in the two groups. In controls, both sublingual glyceryl trinitrate and transdermal glyceryl trinitrate patches significantly reduced platelet aggregation (-38%; 95% CI, -49% to -27%) and blood viscosity (-8%; CI, -11% to -5%) and increased blood filterability (10%; CI, 7.0% to 13.1%). Slight but significant decreases in blood pressure and ejection fraction and an increase in heart rate were also seen in controls after administration of glyceryl trinitrate (both preparations). In patients with diabetes, glyceryl trinitrate paradoxically increased platelet aggregation (24%; CI, 15% to 33%) and blood viscosity (6%; CI, 2.9% to 8.8%) and decreased blood filterability (-7%; CI, -9.5% to -4.4%); hemodynamic values did not change significantly. In both groups, rheologic responses to glyceryl trinitrate (end concentration, 100 and 200 ng/mL) in vitro were similar to those seen in ex vivo studies. Vitamin E and glutathione normalized rheologic responses to glyceryl trinitrate in patients with diabetes. CONCLUSIONS: Organic nitrates have beneficial effects on blood rheology in controls but not in patients with diabetes, in whom a paradoxical deterioration is seen. Antioxidant supplementation can normalize primary tolerance to the rheologic effects of nitrates in diabetes.