Physiological and pharmacological investigations of small intestinal peristalsis

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Organoprotection and cytoprotection of histamine differ in rats

Aims  The aim of the present study was to compare the organoprotective (in vivo) and cytoprotective (in vitro) effects of histamine. Methods  In vivo, gastric mucosal damage was produced by intragastric (ig) administration of 1 ml 96% ethanol (EtOH) in Sprague-Dawley rats. The animals were sacrificed 1 h after EtOH administration, when the gastric mucosal damage was measured. Histamine was given subcutaneously (sc) 30 min before administration of EtOH with and without PGI₂Na (5 μg/kg sc). Gastric acid secretion was also measured 1 h after pylorus ligation in control (saline-), histamine- and PGI₂-treated animals. The affinity, intrinsic activity curves and the values of pD₂ and pA₂ were determined in EtOH-treated and in PGI₂-treated animals. For the in-vitro studies, a mixed population of rat gastric mucosal cells was isolated by pronase digestion. Cells were preincubated for 60 min with histamine (10^♪−8-10⁻⁶ mol/L) with or without PGI₂Na (10⁻⁴ mol/L). At the end of this incubation period, cells were treated with 15% EtOH with or without 10⁻⁶-10³ mol/L indomethacin (IND) for 5 min. Cell viability was tested by trypan blue exclusion test and succinic dehydrogenase activity. Results  

Clinimetrics and epilepsy care

In order to study the practicability of rating scales in the regular care of people with epilepsy, indices have been developed and tested on their validity. These indices consist of the Index of Seizures, representing seizure activity, and the Composite Index of Impairment concerning the severity of impairment caused by the seizure type and frequency and the side-effects of anti-epileptic drug treatment. The indices have been applied in a retrospective quantitative evaluation of anti-epileptic drug therapy. The medical records of 250 randomly selected patients registered at an adult out-patient clinic have been reviewed. Their seizures have been classified as generalized tonic-clonic, simple partial and/or complex partial. The distribution of this population according to these indices has been studied, which leads us to the following conclusions:

Regulatory mechanism of acid secretion in rat stomach after damage-role of nitric oxide, histamine and sensory neurons

The gastric mucosa responds to mucosal damaging agents by significantly decreasing acid secretion. However, the inhibition of nitric oxide (NO) biosynthesis by N^G-nitro-L-arginine methyl ester (l-NAME) turned the acid-secretory response in the damaged stomach from the ‘inhibition’ into ‘stimulation’ state. The present study was performed to investigate the mechanism underlying stimulation of acid secretion in the stomach after damage in the presence of l-NAME. Exposure of the chambered rat stomach to 20 mmol/L taurocholate (TC) for 30 min decreased acid secretion with concomitant reduction of transmucosal potential difference (PD). Pretreatment with L-NAME, although it had no effect on basal acid secretion, apparently increased the acid secretion in the stomach after exposure to TC without any change in the PD response. The acid-stimulatory effect of l -NAME in the damaged stomach was reversed by the co-administration of L-arginine but not D-arginine. Such acid-secretory responses in the presence of L-NAME were also inhibited by prior administration of cimetidine, FPL-52694 (a mast cell stabilizer), spantide (a substance P antagonist) or sensory defunctionalization with capsaicin pretreatment. In contrast, mucosal exposure to TC significantly decreased the number of mucosal mast cells and increased histamine output in the lumen, and these responses were significantly inhibited by FPL-52794, spantide or sensory deafferentation. These findings suggest that:

Effects of sulphasalazine on lymphocyte functions

Sulphasalazine (SASP) is established as a second-line drug in the treatment of rheumatoid arthritis (RA) and some of the seronegative spondarthritides. It is not clear whether the parent compound, one of its two main metabolites or a combination is responsible for its therapeutic effect. Much of the drug’s action is also unknown. Since RA and the seronegative spondarthropathies ail share substantial immunopathology, the immune effects of SASP and/or its main metabolites may play a major part in its action. This paper reviews:

The population pharmacokinetics of theophylline during the early postnatal period

The following conclusions may be drawn from this study's results:

Therapeutic effects of HS-3, HS-6, benactyzine,and atropine in soman poisoning of dogs

Investigations into the therapeutic properties of various combinations of the bispyridinium salts HS-3 and HS-6 and the cholinolytics atropine and benactyzine against soman poisoning in unanesthetized male beagles were performed. In our investigations we observed that:

Quantitative determination of particulate contamination in intravenous administration sets

Particle counts were performed on 1,000 intravenous administration sets from ten suppliers on the Swiss market using a HIAC/Royco electronic counter. The following main conclusions may be drawn from the results of this study:

Unusual case of double acute intoxication with tamoxifen complicated by miscarriage

Background: A 24-year-old female had attempted suicide twice, at the age of 20 and 24, using tamoxifen. Case report: Subsequent to the first acute intoxication a development of bilateral ovarian cysts was observed. Cysts regressed spontaneously within 8 weeks. Five weeks after the second suicidal attempt, pregnant patient (15 weeks of gestation) was admitted to the hospital with vaginal bleeding and suspicion of miscarriage. The autopsy of the fetus did not reveal any gross abnormalities, whereas the microscopic examination demonstrated numerous foci of necrosis in the placental decidua. Other fetal membranes as well as the umbilical cord were normal. Conclusions:

Stereoselectivity of the distribution of labelled noradrenaline in rabbit aortic strips after inhibition of the noradrenaline-metabolizing enzymes

Rabbit aortic strips (nerv--free, reserpinepretreated or normal) whose noradrenaline-metabolizing enzymes were inhibited (by in vitro treatment with 0.5 mM pargyline for 30 min and by the presence of 0.1 mM U-0521) were exposed to 1.18 M labelled (-)- or (+)noradrenaline for 30 min. At the end of the incubation period some strips were used for analysis of radioactivity (i.e., of noradrenaline and its metabolites), while for others the efflux of radioactivity was determined during 250 min of wash out with amine-free solution. An estimate of the original distribution of the amine into the various extraneuronal and neuronal compartments of the tissue was obtained by compartmental analysis of the efflux curves.

Not asthma,but GERD:case report

Asthma is a disorder of the lungs characterized by increased responsiveness of the airways, as manifested by episodes of wheezing and increased resistance to expiratory airflow because of varying degrees of smooth muscle contraction, edema of the mucosa, and mucus in the lumen of the bronchi and bronchioles. The stimuli vary widely and include antigens, infection, air pollutants, respiratory tract irrtants, exercise, and emotional factors. This condition is completely different from distress breathing because of laryngotracheal spasm. One of its causes is the gastric content reflux through the pharynx to the larynx because of gastroesophageal reflux disease (GERD), in addition to the typical human avian flu that may cause immediate suffocation by laryngospasm owing to acute larygotrachitis. A patient suffered from GERD without esophageal symptoms, which was diagnosed and treated as bronchial asthma during his five emergency admissions. The admissions were because of episodic attacks of severe air hunger owing to an extreme throat tightening. The patient was being treated for as long as two years. After the correct diagnosis was made and treatment of laporascopic fundaplication was performed, the longstanding “bronchial asthma”, after all, completely disappeared. The concept of “not asthma, but GERD” seems undervalued, unappreciated, even misunderstood among patients with intractable asthma. Therefore, such a case is reported in detail, similar cases are mentioned briefly as well, and a mechanism responsible for GERD-originated larryngo-or laryngotracho-spasm is proposed.     

Regulation of adrenergic receptor number following chronic noradrenaline infusion in the rabbit

In order to study noradrenaline-induced regulation of alpha- and beta-adrenoceptors, groups of male New Zealand White rabbits (n = 8) were treated with intravenous noradrenaline (0.09 mol/kg × h) or ascorbate (0.1 %) for I0 days via osmotic minipumps implanted in the femoral vein, and the number of cardiac, lung and lymphocyte beta-adrenoceptors as well as renal and platelet alpha₂-adrenoceptors were determined.

Inhibition of receptor-mediated noradrenaline release from the sympathetic nerves of the isolated rabbit heart by anaesthetics and alcohols in proportion to their hydrophobic property

The actions of anaesthetics (diethyl ether, enflurane, chloroform, methoxyflurane) and alcohols (ethanol, 1-propanol, 1-butanol, 1-pentanol) on the noradrenaline release from (and uptake into) the sympathetic nerve terminals were studied in isolated rabbit hearts perfused with Tyrode solution at constant flow rate. The noradrenaline in the perfusate was assayed spectrofluorimetrically.

Innovative Approach to Preparing Radial Artery Cocktails in Response to Manufacturer Shortages of Nitroglycerin and Verapamil

Background:

Transradial access has gained popularity over transfemoral access for cardiac catheterization, because of the decreased risk of bleeding, time to ambulation, and length of stay leading to improved patient satisfaction. One disadvantage of the radial artery approach is vasospasm, which can be prevented with the administration of verapamil and nitroglycerin in a pre- and postradial cocktail. Unfortunately, there have been manufacturer shortages for both of these medications.

Methods:

The utilization of radial artery cocktails and other nitroglycerin compounding practices were evaluated in response to cost containment and waste reduction initiatives and to medication shortages.

Results:

A modified process for supplying verapamil and nitroglycerin for the transradial approach via separate syringes enabled physicians to have quick access to the medications and to customize the cocktail based on the patient’s needs. This process also decreased costs and minimized wastage. The change in practice decreased waste from 44% for preradial cocktail syringes and 66% for postradial cocktail syringes to 8.7%.

Discussion:

This process for supplying the medications necessary to perform a radial artery catheterization and intracoronary nitroglycerin has allowed for conservation of commercial product supply.Key Words: verapamil, cardiac catheterization, drug shortage, nitroglycerin, radial artery spasm, stability, transradialAt The Ohio State University Wexner Medical Center (OSUWMC), 4,000 diagnostic catheterizations and 1,500 percutaneous coronary interventions (PCI) are performed annually. Until September 2010, the transfemoral approach accounted for more than 80% of the access sites used for patients undergoing cardiac catheterization procedures. The transradial approach has gained popularity as a way to decrease the number of post-PCI bleeding complications, access site hematomas, and transfusions as well as to decrease the time to ambulation and length of stay.^1–4In comparison to the femoral artery, the radial artery is significantly smaller, which predisposes the vessel to vasospasm. One of the most frequent complications of patients undergoing the transradial approach is radial artery spasm; this can cause discomfort for the patient during the procedure and can require that the procedure be stopped or the access site changed. There is no standard definition for radial artery spasm and there are differences in techniques used to perform the procedure, but the incidence of vasospasm is estimated to be between 2% and 51.3%.^1–4 Factors other than radial artery spasm can lead to the procedure being stopped or the access site being changed, so the incidence attributable to radial artery spasm alone is not well-established.Intra-arterial administration of vasodilating agents with differing mechanisms of action (ie, verapamil and nitroglycerin) prior to inserting the sheath has been shown to reduce the incidence and severity of radial artery spasm.^3,4 Verapamil works by inhibiting calcium influx and contractility of smooth muscles through selective blockade of the L-type voltage-gated calcium channels; nitroglycerin works by releasing nitric oxide, raising cGMP levels, and reducing the calcium concentration to cause relaxation in the smooth muscle. In addition to vasodilating agents, heparin may be used in the preradial cocktail to prevent thrombus formation that may lead to radial artery occlusion when the wire is inserted.Up to 2012 at OSUWMC, the interventional cardiologists could administer a preradial cocktail containing nitroglycerin 200 mcg, verapamil 2.5 mg, and heparin 2,500 units and a postradial cocktail containing nitroglycerin 200 mcg and verapamil 2.5 mg (see 3 Both syringes were diluted with normal saline to a total volume of 10 mL; they had an arbitrary refrigerated 24-hour default expiration date due to the lack of data showing detrimental degradation within this time period or supportive data extending the storage time. This expiration dating falls within the sterility dating as established by the US Pharmacopeia (USP).⁵ For predrawn syringes, the beyond-use dating for a medium risk level would permit 30 hours at room temperature or 9 days refrigerated without additional sterility testing.

Table 1.

Baseline recipe for pre- and postradial cocktails^3–4

Beyond Gout: Colchicine Use in the Cardiovascular Patient

Colchicine is one of the oldest medications still in use today and is commonly used for the treatment of gout and familial Mediterranean fever. Its anti-inflammatory properties have raised the question of its utility in managing several cardiovascular diseases, including postoperative atrial fibrillation and pericarditis. This article will review the evidence for colchicine in these conditions and provide recommendations for use.Colchicine is one of the oldest known drugs still prescribed today. It is US Food and Drug Administration (FDA)–approved for the treat-ment of familial Mediterranean fever and acute gout and for prophylaxis against gouty arthritis.¹ Colchicine exhibits both antiproliferative and anti-inflammatory actions, primarily via inhibition of microtubule self-assembly through the formation of tubulin-colchicine complexes. This action inhibits the movement of intercellular granules and the secretion of various inflammatory substances. Colchicine has also been found to impair neutrophil adhesion to vascular endothelium. Colchicine shows a preferential concentration for leukocytes, thus decreasing leukocyte motility and blunting the inflammatory response. Peak concentrations in leukocytes may be more than 10 times the peak concentration in plasma; therefore, a therapeutic effect can be seen at relatively low oral doses.²In recent years, colchicine has been evaluated in the management of a number of cardiovascular diseases, most notably the treatment of acute and recurrent pericarditis and prevention of postoperative atrial fibrillation (POAF). In this article, we review the current evidence for colchicine’s role in the treatment of cardiovascular disease and provide recommendations for use. All trials discussed are summarized in