Does short-term treatment with proton pump inhibitors cause rebound aggravation of symptoms?

BACKGROUND: Rebound acid hypersecretion might occur after treatment with proton pump inhibitors. This study looks for a rebound aggravation of symptoms after short-term treatment with lansoprazole. STUDY: Sixty-two patients (19 men and 43 women; mean age, 54 years; range, 32-77 years) with heartburn and regurgitation and normal upper endoscopy findings were studied in a randomized, double-blind, placebo-controlled trial with a crossover design. There were two 5-day treatment periods with lansoprazole 60 mg once daily or placebo in random order, separated by a 9-day washout period. Reflux, total, and antacid scores were calculated for each of the treatment periods. Higher scores during the placebo period in the group given lansoprazole first than in the group given placebo first indicated a rebound aggravation of symptoms. RESULTS: The mean symptom scores during the placebo period in the groups given lansoprazole first and placebo first were as follows: reflux score, 21.5 and 17.6, respectively (not significant); total score, 11.2 and 10.3, respectively (not significant); and antacid score, 8.2 and 7.2, respectively (not significant). CONCLUSIONS: There is no indication of a rebound aggravation of symptoms 12 to 14 days after a 5-day treatment with lansoprazole 60 mg once daily in patients with reflux symptoms.

Primary structure of fox (Vulpes vulpes) proinsulin based on sequence studies of pancreatic peptides and cDNA.

Insulin and C-peptide were extracted and purified from fox (Vulpes vulpes) pancreas using gel filtration, ion-exchange chromatography and HPLC. Chromatographic data for the insulin, as well as for its oxidized and carboxymethylated chains proved it to be identical to that of polar fox (Alopex lagopus) and dog. The sequence analysis of a peptide which was assumed to be the corresponding C-peptide revealed that it comprises 23 amino acid residues and is identical to the C-peptide fragment isolated from dog pancreas: it differs from polar fox C-peptide by a single substitution (Asp-->Glu). mRNA was isolated from pancreatic tissue and cDNA was obtained by reverse transcription. A polymerase chain reaction was performed using gene-specific primers to obtain a DNA fragment corresponding to part of fox proinsulin. DNA sequencing revealed 100% identity to dog proinsulin at the protein level, although some amino acids were encoded by different codons. The total sequence of proinsulin was deduced from these results.

Secretory expression of human albumin domains in Saccharomyces cerevisiae and their binding of myristic acid and an acylated insulin analogue.

Albumin is organized in three homologous domains formed by double loops stabilized by disulfide bonds. Utilizing a secretory expression system based on a synthetic secretory prepro-leader, the three human serum albumin domains were expressed in the yeast Saccharomyces cerevisiae. Human serum albumin domains I and III were efficiently expressed and secreted, indicating that these domains can form independent structural units capable of folding into stable tertiary structures. In contrast, albumin domain II was not secreted and disappeared early in the secretory pathway. Human serum albumin has the ability to bind a large number of small molecule ligands, including fatty acids, presumably due to its structure and structural flexibility. Purified albumin domain III bound myristic acid, whereas purified albumin domain I did not bind myristic acid. A new soluble long-acting insulin an alogue acylated with myristic acid (Markussen J., et al., Diabetologia 39, 281-288, 1996) bound to domain III and bound markedly more weakly to domain I.

Synthetic leaders with potential BiP binding mediate high-yield secretion of correctly folded insulin precursors from Saccharomyces cerevisiae.

Secretion leaders are essential for expression of many heterologous proteins including insulin in yeast. The function of secretion leaders and their interaction with the secretory pathway is not clear. To determine what constitutes functional pre-pro-leader sequences in Saccharomyces cerevisiae, synthetic leader sequences for secretion of the insulin precursor were developed by a combination of rational design and stepwise systematic optimization. The synthetic leaders efficiently facilitate secretion of the insulin precursor from S. cerevisiae when compared with the alpha-factor leader, leading to a high yield of correctly folded insulin precursor in the culture supernatant. The synthetic leaders feature two potential N-linked glycosylation sites which are efficiently glycosylated during secretion. Pulse-chase analysis indicates that the synthetic leaders/insulin precursor fusion protein have a prolonged residence in the endoplasmic reticulum compared to the alpha-factor leader/insulin precursor fusion protein. The longer transition time in the endoplasmic reticulum mediated by the synthetic leaders might provide additional time for correct folding of the insulin precursor and account for the increased fermentation yield.

Novel avidin and streptavidin binding sequences found in synthetic peptide libraries.

Synthetic resin-bound peptide libraries made of protein L-amino acids have been synthesized. During screening of the libraries, peptides that bind to avidin have been identified containing a novel motif with two histidines separated by one residue. A sub-library was synthesized and screened, and new critical residues appeared surrounding the two histidines. Additionally peptide libraries made of D-amino acids have been screened with avidin and streptavidin and novel motifs have been found.

Real time monitoring of acylations during solid phase peptide synthesis: a method based on electrochemical detection.

Monitoring of acylation reactions during solid phase peptide synthesis is important to ensure high coupling yields in all steps of the synthesis. We describe in this paper a simple and reliable method for monitoring the time course of the acylation steps as well as the washing and deprotection steps during computer-controlled solid phase peptide synthesis. The method is based on the continuous measurement of electrical conductivity in the reaction vessel. It is shown that there is a close correspondence between the degree of acylation (as determined from the amount of 9-fluorenylmethoxycarbonyl- (Fmoc) groups released during deprotection) and the conductivity profile obtained during coupling of the amino acids to the growing peptide chain. The measurements are fed back to the computer providing data for software control of the duration of the acylation, deprotection and washing steps. The method is demonstrated with pentafluorophenol esters, but is equally applicable to dihydroxybenzotriazole esters and symmetric anhydrides using the Fmoc-polyamide strategy in a continuous flow set-up with dimethylformamide (DMF) as the general solvent.

Mannitol-induced rebleeding from intracranial aneurysm. Case report.

A case is presented in which rebleeding from an intracranial saccular aneurysm occurred a few minutes after intravenous administration of mannitol during surgery. The relationship between the reducing effect of mannitol on elevated intracranial pressure and the increased pressure gradient across the aneurysm wall, causing risk of rebleeding, is discussed. Procedures that can reduce this risk are summarized.

A new nerve stimulator (Myotest).

The Myotest is a new nerve stimulator which can give train-of-four, single twitch (1 and 10 s) and tetanic stimuli. Power is supplied by standard batteries, which allow 200 h effective use. The impulse is unipolar constant current, and the amplitude can be adjusted between 0 and 40 mA. These factors, plus the electronic control of stimulus administration, make the nerve stimulator easy to use, and facilitate the interpretation of responses, especially to tetanic and post-tetanic stimulation.