Multiple action sites of flufenamate on ion transport across the rat distal colon

The antisecretory effects of flufenamate in the rat distal colon were investigated with the Ussing-chamber and the patch-clamp method as well as by measurements of the intracellular Ca(2+) concentration using fura-2-loaded isolated crypts. Flufenamate (5.10(-4) mol l(-1)) suppressed the short-circuit current (Isc) induced by carbachol (5.10(-5) mol l(-1)), forskolin (5.10(-6) mol l(-1)) and the Isc induced by the membrane-permeable analogue of cyclic AMP, CPT - cyclic AMP (10(-4) mol l(-1)). Indomethacin (10(-6) - 10(-4) mol l(-1)) did not mimic the effect of flufenamate, indicating that the antisecretory effect of flufenamate is not related to the inhibition of the cyclo-oxygenase. When the basolateral membrane was depolarized by a high K(+) concentration and a Cl(-) current was induced by a mucosally directed Cl(-) gradient, the forskolin-stimulated Cl(-) current was blocked by flufenamate, indicating an inhibition of the cyclic AMP-stimulated apical Cl(-) conductance. When the apical membrane was permeabilized by the ionophore, nystatin, flufenamate decreased the basolateral K(+) conductance and inhibited the Na(+) - K(+)-ATPase. Patch-clamp experiments revealed a variable effect of flufenamate on membrane currents. In seven out of 11 crypt cells the drug induced an increase of the K(+) current, whereas in the remaining four cells an inhibition was observed. Experiments with fura-2-loaded isolated crypts indicated that flufenamate increased the basal as well as the carbachol-stimulated intracellular Ca(2+) concentration. These results demonstrate that flufenamate possesses multiple action sites in the rat colon: The apical Cl(-) conductance, basolateral K(+) conductances and the Na(+) - K(+)-ATPase.     

A Clinical Report and Overview of Scientific Studies and Clinical Procedures Conducted on the 3M ESPE Lava™ All-Ceramic System

The Lava All-Ceramic System (3M ESPE Dental Products, St. Paul, MN) is a high-strength zirconia system, which can be utilized to create all-ceramic crowns and fixed partial dentures (FPDs) for use in the anterior and posterior regions of the oral cavity. The following study offers an overview of previously conducted scientific studies and clinical procedures that feature the Lava All-Ceramic System as well as a more general overview of zirconia ceramics. A clinical report demonstrates the use of the Lava All-Ceramic System with the restoration of 2 single crowns.     

Cholinergic-mediated secretion in the rat colon: neuronal and epithelial muscarinic responses

The acetylcholine receptor agonists, acetylcholine (10(-5)-10(-4 M), carbachol (5 x 10(-6)-5 x 10(-5) M), bethanechol (5 x 10(-5)-5 x 10(-4) M) and dimethylphenylpiperazinium (DMPP, 10(-5) M) increased the short-circuit current (Isc) in the rat colon descendens by a tetrodotoxin (TTX)-sensitive mechanism. Blockade by TTX was still observed after removal of the submucosa, indicating the involvement of neurons of the mucosal plexus. Hexamethonium (10(-5) M) and atropine (10(-6) M) were used to distinguish between nicotinic and muscarinic neuronally mediated effects. The inhibitor of choline uptake, hemicholinium-3 (1 mM), reversibly inhibited the effect of repeated electric field stimulation (EFS). The EFS response was only inhibited by high concentrations of atropine (greater than or equal to 10(-5) M). In mucosa-submucosa preparations 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP) was more effective than telenzepine whereas pirenzepine was ineffective. Pirenzepine inhibited the EFS response in mucosa preparations as did telenzepine and 4-DAMP. It was not possible to differentiate between the muscarinic receptors involved in the different parts of the enteric nervous system on the basis of our results.     

Therapie der Migräneattacke

Zusammenfassung Die Inzidenz der Migr?ne betr?gt 6–8% für M?nner und 12–14% für Frauen. Die Attacken gehen mit pulsierenden, pochenden, halbseitigen Kopfschmerzen und vegetativen Begleiterscheinungen einher. Bei ca. 15% der Patienten kommt es vor den Kopfschmerzen zu einer Aura, meist mit visuellen Symptomen. Leichte und mittelschwere Migr?neattacken werden mit der Kombination eines prokinetischen Antiemetikums wie Metoclopramid oder Domperidon und einem ausreichend dosierten Analgetikum (Azetylsalizyls?ure, Paracetamol, Ibuprofen, Naproxen, Diclofenac) behandelt. Mittelschwere und schwere Migr?neattacken werden mit den modernen 5-HT_1B/D-Rezeptoragonisten (“Triptane”) behandelt. Die Kombination eines Antiemetikums und Ergotamintartrat ist weniger wirksam als die “Triptane”.     

Nitrate and nitrite content of the saliva, urine, blood and cerebrospinal fluid in patients at an infection clinic

In 254 patients of a ward for infectious diseases the authors demonstrated that inflammatory diseases are frequently accompanied by an increase in nitrate content of the blood, urine and saliva. This effect is especially evident in gastrointestinal disorders. Correlations of nitrate with indicators of the inflammatory process are, if at all, very weak. The endogenous synthesis of nitrate may be of importance for the total nitrate load to the organism especially in children or patients with long-lasting inflammatory disease.     

Analysis of the interchangeability of a dental articulator

A series of Dentatus ARL articulators and gauge blocks were tested for the reliability of the system to reproduce articulator mountings. Points of occlusal contact were measured at several locations on a set of casts. Analysis of the data indicated that the location of the occlusal contacts and the gauge block used were critically related to the results. Further studies to quantify the measurement error and to carefully explore where this system could be used are needed.     

Effects of Long-Term Antihypertensive Therapy with Losartan on Blood Pressure and Cognitive Function in Patients with Essential Hypertension and Other Cerebrovascular Risk Factors (AWARE Observational Study).]

BACKGROUND AND PURPOSE: As arterial hypertension is the most important risk factor for ischemic stroke, the relevant guidelines recommend rigorous treatment to normalize blood pressure. Hypertension can also be associated with cognitive decline and dementia. Therefore, the effect of a long-term therapy with the AT(1) antagonist losartan (+/- hydro chloro thiazide [HCTZ]) on cognitive function in patients with essential hypertension and additional cerebrovascular risk factors was investigated. PATIENTS AND METHODS: Prospective, open observational study in 6,206 adult patients with known essential hypertension and cerebrovascular risk factors (most with a 10-year stroke risk of >/= 20% based on the Framingham Score). Demographic data, blood pressure, selected laboratory parameters, and cognitive function (c.I. test) were determined at baseline and after 3, 6, and 12 months. RESULTS: The patients' mean age was 65.8 +/- 10.7 years and 46.1% of the patients were male. In addition to treatment with losartan +/- HCTZ, 54.1% of the patients received one or more additional antihypertensive agents. After 1 year of treatment, systolic/diastolic blood pressure fell from its baseline level of 158.1/90.3 mmHg to 137.3/80.6 mmHg (-20.8/-9.7 mmHg). The proportion of patients with no/mild/severe cognitive impairment was 30.0%/30.3%/39.7% at baseline and 34.8%/28.1%/37.1% at the end of the study. In patients with cognitive impairment, fibrinogen and hsCRP (high-sensitive C-reactive protein) levels were significantly elevated. Adverse events (AEs) were reported in 231 patients (3.7%), while serious/nonserious AEs possibly related to the study medication were reported in only six (0.1%) and 38 patients (0.6%), respectively. CONCLUSION: A high proportion of patients with hypertension shows cognitive impair ment; therefore, use of appropriate tests to detect this should be considered. The losartan-based antihypertensive treatment increased the proportion of patients with normal cognitive function, reduced blood pressure, and was well tolerated in the primary-care setting.