ABSTRACT
BACKGROUND: Some reports have suggested an association between dopamine agonists and hiccups, involuntary contractions that merit full clinical attention because they can be very debilitating. Many drugs frequently used to treat hiccups are formally contraindicated in Parkinson's disease due to their liability to worsen motor symptoms, making the treatment of hiccups problematic in this disease. The objective of the present study was to analyze all spontaneous reports of hiccups from the European Pharmacovigilance Database in patients with Parkinson's disease and/or on dopaminergic drugs. Finally, we sought to identify evidence-based recommendations on the management of hiccups in Parkinson's disease. METHODS: We searched for all reports of hiccups in the European Pharmacovigilance Database (EudraVigilance) and calculated proportional reporting ratios for dopamine agonists and hiccups. We reviewed the literature on Parkinson's disease, dopamine agonists, and hiccups, searching for specific treatment recommendations for hiccups in this disease. RESULTS: Both rotigotine and pramipexole fulfilled the criteria to generate a safety signal. We found 32 and 13 cases of hiccups associated with dopamine agonists in EudraVigilance and the literature, respectively. There were no specific recommendations for the management of hiccups in Parkinson's disease in the clinical guidelines consulted. CONCLUSIONS: We have found evidence that rotigotine and pramipexole are associated with the appearance of hiccups and that this adverse reaction occurs predominantly in males. Given the scarce information available, specific recommendations are needed in clinical guidelines for the adequate management of hiccups in Parkinson's disease.
Subject(s)
Benzothiazoles/adverse effects , Dopamine Agonists/adverse effects , Hiccup/chemically induced , Parkinson Disease/drug therapy , Tetrahydronaphthalenes/adverse effects , Thiophenes/adverse effects , Aged , Aged, 80 and over , Benzothiazoles/therapeutic use , Dopamine Agonists/therapeutic use , Female , Humans , Male , Middle Aged , Pharmacovigilance , Pramipexole , Tetrahydronaphthalenes/therapeutic use , Thiophenes/therapeutic useABSTRACT
The decapacitating fraction of human seminal plasma, which strongly interacts with concanavalin A, is constituted by high mannose-type N-linked glycoproteins, most of them of less than 44 kDa. Each component with apparent molecular mass of 30, 18, and 17 kDa respectively, as judged by SDS-PAGE, was submitted to "in gel" digestion with trypsin followed by HPLC separation of the peptides and sequencing. They were characterized at microscale as gp17, an aspartyl protease that possibly contributes to liquefaction of the seminal plasma coagulum, two fragments of human acid phosphatase (17 and 30 kDa, respectively), and a 17-kDa fragment of carboxypeptidase E. Neither the fragments of prostatic acid phosphatase nor that of carboxypeptidase E had been described before in the human seminal fluid. Very weak bands, of apparent molecular masses 44 and 52 kDa, are consistent with presence of small amounts of parent compounds, prostatic acid phosphatase and carboxypeptidase E.
Subject(s)
Carboxypeptidase H/isolation & purification , Concanavalin A/metabolism , Glycoproteins/isolation & purification , Peptide Fragments/isolation & purification , Protein Tyrosine Phosphatases/isolation & purification , Semen/chemistry , Acid Phosphatase , Amino Acid Sequence , Carboxypeptidase H/metabolism , Chromatography, Affinity , Chromatography, High Pressure Liquid , Glycoproteins/chemistry , Glycoproteins/metabolism , Humans , Molecular Sequence Data , Molecular Weight , Peptide Fragments/metabolism , Protein Tyrosine Phosphatases/chemistry , Protein Tyrosine Phosphatases/metabolism , Semen/enzymologyABSTRACT
These studies showed that the fractionation of bovine seminal plasma based on lectin agarose affinity chromatography, employing lectins specific to asparagine linked oligosaccharides, and a lectin specific for fucosylated glycans, lead to products with an inhibitory effect on the acrosine-like protease activity. This effect decreases when glycocompounds containing fucosylated Lewis(x) structures are removed, suggesting that these compounds might have some role in the modulation of this activity in the bull. In the fraction devoid of high mannose, hybrid and non-bisecting lactosaminic oligosaccharide-containing glycocompounds, PDC-109 and aSFP proteins were detected and characterized at microscale.
Subject(s)
Chromatography, Affinity/methods , Endopeptidases/metabolism , Protease Inhibitors/pharmacology , Proteins/analysis , Proteins/chemistry , Semen/chemistry , Amino Acid Sequence , Animals , Cattle , Chromatography, Gel , Electrophoresis, Polyacrylamide Gel , Endopeptidases/chemistry , Lectins/chemistry , Male , Protease Inhibitors/chemistry , Seminal Plasma ProteinsABSTRACT
Fucosylated glycoconjugates play an important role in fertilization as the recognition signal of the zona pellucida. In this work, using "critical" concentrations of either, FITC Lotus tetragonolobus lectin or FITC alpha-L-fucosyl-BSA neoglycoprotein as molecular probes, population densities of fucosylated glycoconjugates and of their "complementary" molecules (carrying fucosyl receptors), were found all over the sperm surface with higher population densities in post acrosomal sheath, neck and midpiece. These results were compared with previously reported data on the population densities of lactosaminic compounds and their "complementary" molecules, obtained on same samples of spermatozoa. Statistical data demonstrate that fucosylated glycoconjugates share the same domains with biantennary N-acetyllactosaminic oligosaccharides carrying outer galactose and bisected N-acetylglucosamine residues. These domains highly differ with those of the lactosaminic glycoproteins carrying tri and tetraantennary N-acetyllactosaminic oligosaccharides. These studies also show that the domains of fucosylated glycoconjugates and their "complementary" molecules (carrying fucosyl receptors) locate in different zones of the spermatozoon than those of the compounds carrying beta-galactosyl receptors. Besides, the results suggest structural differences between fucosylated glycoconjugates of the acrosome, equatorial zone and post acrosomal sheath. This may be relevant to the different biological behavior of these compounds and zones, in fertilization.
Subject(s)
Amino Sugars/chemistry , Fucose/chemistry , Galactose/chemistry , Glycoconjugates/chemistry , Spermatozoa/chemistry , Amino Sugars/metabolism , Binding Sites/physiology , Fluorescein-5-isothiocyanate , Follicle Stimulating Hormone/chemistry , Follicle Stimulating Hormone/metabolism , Fucose/metabolism , Galactose/metabolism , Glycoconjugates/metabolism , Humans , Lectins , Luteinizing Hormone/chemistry , Luteinizing Hormone/metabolism , Male , Protein Structure, Tertiary , Spermatozoa/ultrastructureABSTRACT
Fucosylated glycoconjugates play an important role in fertilization as the recognition signal of the zona pellucida. In this work, using "critical" concentrations of either, FITC Lotus tetragonolobus lectin or FITC alpha-L-fucosyl-BSA neoglycoprotein as molecular probes, population densities of fucosylated glycoconjugates and of their "complementary" molecules (carrying fucosyl receptors), were found all over the sperm surface with higher population densities in post acrosomal sheath, neck and midpiece. These results were compared with previously reported data on the population densities of lactosaminic compounds and their "complementary" molecules, obtained on same samples of spermatozoa. Statistical data demonstrate that fucosylated glycoconjugates share the same domains with biantennary N-acetyllactosaminic oligosaccharides carrying outer galactose and bisected N-acetylglucosamine residues. These domains highly differ with those of the lactosaminic glycoproteins carrying tri and tetraantennary N-acetyllactosaminic oligosaccharides. These studies also show that the domains of fucosylated glycoconjugates and their "complementary" molecules (carrying fucosyl receptors) locate in different zones of the spermatozoon than those of the compounds carrying beta-galactosyl receptors. Besides, the results suggest structural differences between fucosylated glycoconjugates of the acrosome, equatorial zone and post acrosomal sheath. This may be relevant to the different biological behavior of these compounds and zones, in fertilization.(AU)
Subject(s)
Comparative Study , Humans , Male , RESEARCH SUPPORT, NON-U.S. GOVT , Amino Sugars/chemistry , Fucose/chemistry , Galactose/chemistry , Glycoconjugates/chemistry , Spermatozoa/chemistry , Amino Sugars/metabolism , Binding Sites/physiology , Fluorescein-5-isothiocyanate , Follicle Stimulating Hormone/chemistry , Follicle Stimulating Hormone/metabolism , Fucose/metabolism , Galactose/metabolism , Glycoconjugates/metabolism , Lectins , Luteinizing Hormone/chemistry , Luteinizing Hormone/metabolism , Protein Structure, Tertiary , Spermatozoa/ultrastructureABSTRACT
Fucosylated glycoconjugates play an important role in fertilization as the recognition signal of the zona pellucida. In this work, using "critical" concentrations of either, FITC Lotus tetragonolobus lectin or FITC alpha-L-fucosyl-BSA neoglycoprotein as molecular probes, population densities of fucosylated glycoconjugates and of their "complementary" molecules (carrying fucosyl receptors), were found all over the sperm surface with higher population densities in post acrosomal sheath, neck and midpiece. These results were compared with previously reported data on the population densities of lactosaminic compounds and their "complementary" molecules, obtained on same samples of spermatozoa. Statistical data demonstrate that fucosylated glycoconjugates share the same domains with biantennary N-acetyllactosaminic oligosaccharides carrying outer galactose and bisected N-acetylglucosamine residues. These domains highly differ with those of the lactosaminic glycoproteins carrying tri and tetraantennary N-acetyllactosaminic oligosaccharides. These studies also show that the domains of fucosylated glycoconjugates and their "complementary" molecules (carrying fucosyl receptors) locate in different zones of the spermatozoon than those of the compounds carrying beta-galactosyl receptors. Besides, the results suggest structural differences between fucosylated glycoconjugates of the acrosome, equatorial zone and post acrosomal sheath. This may be relevant to the different biological behavior of these compounds and zones, in fertilization.
