Helicobacter pylori and Gastric Cancer: An Overrated Risk?

Objective: As recently suggested, nitric oxide (NO) may play an important role in the regulation of esophageal motility, being partly responsible for the latency period and latency gradient between the onset of a swallow and contractions of esophageal circular smooth muscles. Diffuse esophageal spasm appears to be a classical example in which the mechanisms normally responsible for the physiologic timing of the contractions occurring in the esophageal body after swallowing are disturbed. Methods: Five patients (one male and four female; age, 18-48 years) with symptomatic esophageal spasm were given glyceryl trinitrate (GTN) intravenously in gradually increasing doses or L-arginine on two separate occasions and underwent manometric measurements of esophageal motility after wet swallows, using a multilumen perfused catheter system (Synectics Medical, Stockholm, Sweden). The amplitude, duration, and propagation of the contractions and the latency period were analyzed, using specially designed software. Additionally, during the GTN infusion period arterial blood pressure was measured every 5 min. Results: GTN given at a dose of 100 to 200 μg/kg-h intravenously caused the occurrence of and a dose-dependent elongation of the latency period after swallowing. The mean amplitude of the contractions did not show any significant alterations, whereas the mean duration of the contractions decreased significantly, from 11.2±4.8 sec to 5.4 ± 0.8sec. These effects were accompanied by significant alleviation of symptoms during swallowing. Interestingly, no adverse side effects such as headache or flush were observed at any dose of GTN. The blood pressure did not show any changes during the studies in any of the five patients. Administration of L-arginine (300 mg/kg-h intravenously) did not cause any significant alterations of motility pattern or alleviation of dysphagia. Conclusions: 1) NO may play an important role in the control of human esophageal motility, being involved in the mechanisms responsible for the timing of propulsive contractions in the esophageal body after swallowing; 2) GTN may to be of benefit in the treatment of diffuse esophageal spasm in symptomatic patients; and 3) patients with diffuse esophageal spasm may have a malfunction in endogenous NO synthesis and/or degradation.     

Structural and thermal characterization of glyceryl behenate by X-ray diffraction coupled to differential calorimetry and infrared spectroscopy

Physical and thermal properties of glyceryl behenate (Compritol 888 ATO) used as sustained-release matrix in pharmaceutical applications are studied by coupled time-resolved synchrotron X-ray diffraction and Differential Scanning Calorimetry combined with Infrared Spectroscopy. With these techniques, all polymorphs formed in glyceryl behenate, analyzed as received and after various thermal treatments from quenching to slow crystallization, are characterized. By using different well-controlled mixtures of mono-, di- and tribehenate, we identify each lamellar phase observed in the glyceryl behenate. Finally the influence of the crystallization rate on the formation of preferential conformations was also analyzed in order to bring insights into the polymorphism of glyceryl behenate. By changing the crystallization rate of the sample, it was shown that one can favor the formation of preferential polymorphs in the sample. In particular the crystallization at 10 degrees C/min seems to be well adapted for producing a single lamellar phase with a period of 60.9 A while a crystallization rate of 0.4 degrees C/min produces three different lamellar phases.     

A review of chronic anal fissure management

Anal fissure management has rapidly progressed in the last 15 years as our understanding of fissure pathophysiology has developed. All methods of treatment aim to reduce the anal sphincter spasm associated with chronic anal fissures. Surgical techniques have been used for over 100 years with success. Lateral internal sphincterotomy remains the surgical treatment of choice for many practitioners. Postoperative impairment of continence remains controversial. Recently, less invasive methods of treatment have been explored. Topical nitrates, calcium channel blockers and botulinum toxin are established treatments. These and other non-surgical treatments are described in this review. Various guidelines and treatment algorithms for anal fissure are also discussed.     

奥曲肽联合硝酸甘油治疗肝硬化静脉曲张出血的疗效分析

目的观察奥曲肽联合硝酸甘油对肝硬化静脉曲张出血患者的疗效。方法选择120例肝硬化静脉曲张患者,随机分为二组,治疗组60例,给予奥曲肽联合硝酸甘油为主的治疗,对照组60例给予以奥曲肽为主的治疗。治疗2周,观察其疗效。结果治疗前后两组患者门静脉血流量的降低值和脾静脉血流量降低值比较有显著性差异;两组治愈率,平均止血时间及疗效差别比较具有统计学意义（P〈0.05）。结论奥曲肽联合硝酸甘油治疗组治疗肝硬化静脉曲张出血的疗效优于单用奥曲肽的治疗组。     

Effect of nitric oxide on gallbladder motility in patients with acalculous biliary pain: a cholescintigraphic study

The aim of the present study was to evaluate the influence of the exogenous nitric oxide donor glyceryl trinitrate on cerulein-induced gallbladder contraction in patients with acalculous biliary pain. Quantitative hepatobiliary scintigraphy was performed on 33 patients. From the 60th min cerulein (1 ng/kg body wt/min for 10 min intravenous) then from the 90th min the same dose of cerulein plus glyceryl trinitrate (0.5 mg sublingually) (21 patients) or placebo (12 patients) were administered and the gallbladder ejection fraction was measured repeatedly. After the first dose of caerulein, the gallbladder ejection fraction was less than 35% in 23 of 33 patients (nonresponders), while it was more than 35% in the remaining 10 patients (responders). After the second dose of cerulein in 16 nonresponder patients glyceryl trinitrate administration significantly increased the previously impaired gallbladder ejection fraction while in 7 nonresponder patients placebo administration had no effect. In conclusion, normalization of the gallbladder ejection fraction in the majority of patients following glyceryl trinitrate administration suggests that impairment of gallbladder emptying is caused by a functional motility disorder rather than any organic disease.     

CUT OR PASTE? THE USE OF GLYCERYL TRINITRATE PASTE IN THE TREATMENT OF ACUTE AND CHRONIC ANAL FISSURE

Background : Anal fissure unresponsive to conservative measures such as stool softeners frequently requires surgical intervention. The present study describes the use of glyceryl trinitrate (GTN) in the treatment of acute and chronic anal fissure. Methods : Eighteen consecutive patients with anal fissure were treated with 0.5% GTN paste in soft white paraffin applied twice daily to the anus. These patients were followed at regular intervals to assess symptom control, rate of healing, adverse effects and recurrence rate. Results : Two patients were lost to follow‐up. Twelve of the remaining 16 were cured. Of these, symptomatic relief was obtained for most within 2 days, and for all within 1 week. No patient required cessation of treatment due to adverse effects. Treatment failed in four of 16 patients. Two of these patients subsequently underwent successful surgical procedures, and two patients (while not completely cured) had sufficient symptomatic relief to decide against surgery. Conclusions : The use of GTN paste in the treatment of acute and chronic anal fissure may be a safe and effective modality that can be considered as first‐line treatment for this condition.     

EFFECT OF TOLERANCE TO GLYCERYL TRINITRATE ON VASCULAR RESPONSES IN CONSCIOUS RABBITS

1. The effect of tolerance to glyceryl trinitrate (GTN) on vasodilator and vasoconstrictor responses was examined in conscious rabbits and isolated rabbit aortic rings. 2. In conscious rabbits, depressor responses to 5 min infusions of GTN (10-40 micrograms/kg per min intravenously (i.v.)), sodium nitroprusside (SNP, 5-20 micrograms/kg per min i.v.) and acetylcholine (ACh, 3-12 micrograms/kg per min i.v.) were examined before and after transdermal treatment with GTN (20 mg/48 h). GTN pretreatment significantly attenuated GTN-induced depressor responses, indicating the development of tolerance, but did not affect the reductions in arterial pressure induced by SNP or ACh. 3. Similarly, aortic rings taken from GTN pretreated rabbits exhibited tolerance to GTN but the relaxant responses to SNP or the calcium ionophore A23187 were not affected. In the aortic rings from GTN-tolerant rabbits contractile responses to serotonin or the thromboxane-mimetic U46619 were significantly attenuated, in contrast to the responses to the alpha 1-adrenoceptor agonist phenylephrine (PE) which were significantly enhanced. 4. Similarly, in conscious rabbits, PE-induced increases in arterial pressure and hindlimb vascular resistance were significantly enhanced by GTN pretreatment but the responses to the alpha 2-adrenoceptor agonist BHT 920 were unaffected. 5. In conclusion, tolerance to GTN does not affect endothelium-dependent vasodilatation but does cause a selective enhancement of alpha 1- but not alpha 2-adrenoceptor-mediated vasoconstriction.     

The effect of nitric oxide-donating vasodilators on monocyte chemotaxis and intracellular cGMP concentrations in vitro

Summary The effects of sodium nitroprusside (SNP) and 3-morpholino sydnonimine (SIN-1), isosorbide dinitrate (ISDN) and glyceryl trinitrate (GTN), and molsidomine (the inactive precursur of SIN-1) on monocyte chemotaxis and cyclic GMP (cGMP) concentration were studied.SNP and SIN-1 inhibited monocyte N-formyl-methionyl-leucyl-phenylalanine-stimulated migration and increased cGMP concenrations in a dose-dependent (>10^–5 mol·l^–1) and time-dependent manner. Furthermore, 8-bromo cGMP inhibited monocyte chemotaxis in a dose-dependent fashion. In contrast, ISDN, GTN and molsidomine did not alter monocyte migration or cGMP concentration.These results support earlier observations that nitric oxide inhibits monocyte function in vitro via a cGMP-mediated mechanism.The differential effects of the spontaneous and thiol-dependent NO-donating nitrovasodilators on monocyte function suggests that monocytes, like platelets, are not able to directly metabolise ISDN and GTN. If similar observations can be made in vivo, it is possible that certain nitrovasodilators might be used therapeutically to inhibit monocyte function, for example during atherogenesis.