This phase III, investigator-blind, randomized, parallel-group study compared the efficacy and tolerability of clarithromycin modified release (MR) with those of amoxicillin/clavulanic acid in 250 adult outpatients with acute exacerbationof chronic bronchitis (AECB). Patients received either clarithromycin MR 500 mg once daily or amoxicillin/clavulanic acid 500 mg/125 mg three times daily for 7 days. Primary endpoints were sponsor-defined clinical response and pathogen outcome at the end of treatment. Secondary endpoints were sponsor-defined clinical response and pathogen outcome at study end, investigator-defined clinical response at end of treatment and end of study, resolution or improvement of signs and symptoms, eradication of baseline pathogens, serologic outcome for atypical pathogens, and occurrence of reinfection and superinfection. Adverse events and compliance were also evaluated. Clinical and bacteriologic outcomes with both treatments for all endpoints were statistically equivalent, as were total adverse events, although the incidences of digestive disturbances (13% vs 4%) and discontinuations due to adverse events (8 vs 2 patients; P < or =.05) were significantly higher with amoxicillin/clavulanic acid. Ninety-five percent of patients receiving clarithromycin MR and 80% receiving amoxicillin/clavulanic acid were 100% compliant with medication (P < or =.05). Clarithromycin MR and amoxicillin/clavulanic acid are both well tolerated and effective as therapy for AECB; however, clarithromycin produced fewer side effects and discontinuations and higher compliance rates.

Amoxicillin-Potassium Clavulanate Combination↗

PubMedDate not supplied

LHRH-like immunoreactivity in the human placenta is not identical to LHRH.

LHRH-like immunoreactive material was separated from human placental homogenates by chromatography and tested against two antibodies directed respectively against the C- or the N-terminus (N- and C-antibodies) of the synthetic peptide. Extraction yield was 94 per cent as assessed by the recovery of the radiolabelled LHRH added to the homogenates. Placental LHRH-like immunoreactivity in crude extracts appeared largely overestimated, due to interference of endogenous substances non-related to LHRH. After elimination of this contamination, a higher residual activity was detected with the C- than with the N-antibodies. Eluates tested under these conditions contained only 550 pg of LHRH-like material per kg of placenta. This concentration was comparable whether placental tissue had been sampled at 12 weeks of pregnancy or at the end of gestation. The corresponding peptides however neither co-eluted with synthetic LHRH nor with catabolite fragments of the peptide. It is concluded that the human placenta contains a lesser amount of LHRH-like material than anticipated on the basis of earlier results and that this material does not correspond to the native decapeptide.

Antibody Specificity↗

PubMedDate not supplied

Possible role of neuropeptide degrading enzymes on thyroliberin secretion in fetal hypothalamic cultures grown in serum free medium.

In the present work, we have looked for the presence of two tissular neuropeptide degrading activities, the pyroglutamate aminopeptidase (PAP) and the post-proline cleaving enzyme (PPCE), in dissociated brain cell cultures. These two activities are present in extracts of cells grown in serum-free medium and are detected at a very low level in incubation media. Depolarization of hypothalamic neurons by 60 mM K+ does not specifically increase the level of PAP and PPCE in the medium. We have also used an inhibitor of PPCE: Z-Gly-ProCHN2. This compound can be left in contact with living cells without any toxicity, and in certain conditions of incubation blocks totally and irreversibly both PAP and PPCE. This blockade results in increased levels of TRH, intracellular as well as released into the medium, spontaneously and upon K+ depolarization. These results evidence the role of degradation processes in the mechanisms regulating peptide turn-over.

Aminopeptidases↗

PubMedDate not supplied

Adenohypophyseal degradation of thyrotropin releasing hormone regulated by thyroid hormones.

Thyrotropin Releasing Hormone (TRH; pyroGlu-His-Pro-NH2) is important in the regulation of adenohypophyseal hormone secretion and also serves neurotropic functions in extra-hypothalamic brain areas, indicating that it is involved in neurotransmission and other forms of cellular communication. This hypothesis is strengthened by the observation that TRH is hydrolysed at the pyroGlu-His bond by a particulate enzyme located in the synaptosomal and adenohypophyseal plasma membrane. Furthermore, this enzyme has been identified as a heterogeneously distributed ectoenzyme which has a high degree of substrate specificity like the TRH-degrading serum enzyme studied previously. In the rat, the activity of the TRH-degrading serum enzyme has been shown to be influenced by the thyroid status of the animals; here I report that the activity of the membrane-bound TRH-degrading enzyme of the anterior pituitary is stringently controlled by thyroid hormones, but that the activity of the brain enzyme is not.

Animals↗