A spectroscopic and molecular dynamics study on the aggregation process of a long-acting lipidated therapeutic peptide: the case of semaglutide.

The aggregation properties of semaglutide, a lipidated peptide drug agonist of the Glucagon-like peptide 1 receptor recently approved for the treatment of type 2 diabetes, have been investigated by spectroscopic techniques (UV-Vis absorption, steady-state and time-resolved fluorescence, and electronic circular dichroism) and molecular dynamics simulations. We show that in the micromolar concentration region, in aqueous solution, semaglutide is present as monomeric and dimeric species, with a characteristic monomer-to-dimer transition occurring at around 20 µM. The lipid chain stabilizes a globular morphology of the monomer and dimer species, giving rise to a locally well-defined polar outer surface where the lipid and peptide portions are packed to each other. At very long times, these peptide clusters nucleate the growth of larger aggregates characterized by blue luminescence and a ß-sheet arrangement of the peptide chains. The understanding of the oligomerization and aggregation potential of peptide candidates is key for the development of long acting and stable drugs.

Stapedial reflex and radionuclide investigation of submandibular salivary glands in Bell's palsy.

We compared the prognostic value of the stapedial reflex and the results of submandibular salivary gland scintigraphy in 14 cases of Bell's Palsy.

Epidemiologic features of intestinal parasitic infections in Italian mental institutions.

To determine the prevalence of intestinal parasitic infections in the residents of four Italian psychiatric institutions, we examined the stool specimens collected in triplicate from 238 residents, enrolled between May 1995 and May 1996. Besides, physician and staff nurses provided data about each resident by standardized questionnaires. Parasites were detected in the fecal samples from 128 patients (53.8%). However, in the stool specimens from 106 residents only non-pathogenic protozoa were found (82.8%). Trichuris trichiura ova, Giardia lamblia cysts and trophozoites, Cryptosporidium parvum oocysts, and Balantidium coli cysts were found in the fecal samples from 22 residents (9.2%). B. hominis was the most prevalent parasite. It was detected in the fecal specimens from 97 residents (40.8%). The so-called nonpathogenic amebae were detected in the fecal specimens from 65 residents, though, at the same time, there was no evidence of Entamoeba histolytica infection. Twelve residents (5.0%) showed intestinal colonization by nonpathogenic flagellates. All the subjects with T. trichiura infection were housed in the facility of Ancona. Parasites were found in fecal samples from all the 11 residents with behavioural aberrations, but only three of those suffering from intestinal pathogen infection associated to diarrhea. Statistical analyses revealed that the presence of pathogenic parasites in fecal specimens was significantly associated with diarrhea, nausea, vomiting, abdominal pain, fever, behavioural aberrations and nonpathogenic protozoa (p < 0.01), but did not demonstrate any other significant associations between these parasites and the other variables, such as pruritus, mucus or blood in the stools and presence of fecal leukocytes. On the other hand, the presence of nonpathogenic protozoa was significantly related to aberrations such as pica, geophagia, phytophagy, coprophagy, coprophilia and pathogenic parasites (p < 0.01). Data analyses revealed that both pathogenic and nonpathogenic parasites were significantly more common in institutionalized patients than in controls. The rare presence of clinical signs and symptoms in colonized patients represents an important public health problem, since the presence of asymptomatic carriers among residents with low hygienic conditions, raises concern of transmission of parasitic infections to professional staff and other residents. Since the eradication of parasitic colonization in residential facilities is hard to reach, an effective prevention is the only measure to deal with this public health problem.