ABSTRACT
Pseudomonas aeruginosa (PA) can cause infections in compromised hosts by interacting with the glycocalyx of host epithelial cells. It binds to glycostructures on mucosal surfaces via two lectins, which are carbohydrate-binding proteins, named PA-IL and PA-IIL, and blocking this interaction is, thus, an attractive anti-adhesive strategy. The aim of this study was to determine by ciliary beat frequency (CBF) analysis whether monosaccharides or peptides mimicking glycostructures represent blockers of PA lectin binding to human airway cilia. The treatment with monosaccharides and peptides alone did not change the CBF compared to controls and the tested compounds did not influence the cell morphology or survival, with the exception of peptide pOM3. PA-IL caused a decrease of the CBF within 24 h. D-galactose as well as the peptides mimicking HNK-1, polysialic acid and fucose compensated the CBF-modulating effect of PA-IL with different affinities. PA-IIL also bound to the human airway cilia in cell culture and resulted in a decrease of the CBF within 24 h. L(-)-fucose and pHNK-1 blocked the CBF-decreasing effect of PA-IIL. The HNK-1-specific glycomimetic peptide had a high affinity for binding to both PA-IL and PA-IIL, and inhibited the ciliotoxic effect of both lectins, thus, making it a strong candidate for a therapeutic anti-adhesive drug.
Subject(s)
Cilia/drug effects , Lectins/antagonists & inhibitors , Monosaccharides/pharmacology , Peptides/pharmacology , Pseudomonas aeruginosa/metabolism , Adhesins, Bacterial/metabolism , Amino Acid Sequence , Bacterial Adhesion/drug effects , Bacterial Proteins/metabolism , Binding Sites , Bronchi/metabolism , Bronchi/microbiology , CD57 Antigens/chemistry , CD57 Antigens/metabolism , Cilia/metabolism , Fucose/chemistry , Fucose/metabolism , Galactose/chemistry , Galactose/metabolism , Humans , Lectins/metabolism , Molecular Mimicry , Molecular Sequence Data , Peptides/chemistry , Pseudomonas aeruginosa/pathogenicityABSTRACT
OBJECTIVE: The authors evaluated the diagnostic validity of an interview-based panic disorder diagnosis in cardiology chest pain patients with angiographically normal coronary arteries. METHOD: Patient probands with normal coronary arteries (N = 65) were first contracted immediately after their normal angiogram and were given a structured diagnostic interview. On the basis of the results of the interview, probands were grouped as having panic disorder (N = 19), panic attacks that did not meet frequency criteria for panic disorder (N = 17), or no panic (N = 29). At a later time, patient probands were recontacted and given a structured family history interview that inquired about psychopathology in their first-degree biological relatives (N = 544). RESULTS: As predicted, panic disorder was significantly more prevalent among the first-degree relatives of probands with normal coronary arteries diagnosed with panic disorder or panic attacks than among the family members of probands with normal coronary arteries without panic (17.4% versus 15.7% versus 4.0%). Family members of probands with panic attacks were significantly more likely to be diagnosed with major depression than were the family members of probands with no panic; however, differences did not reach significance for family members of the panic disorder proband group. Groups did not differ significantly in familial alcoholism. CONCLUSIONS: These data support the construct validity of an interview-based panic disorder diagnosis among patients with chest pain and normal coronary arteries and suggest that these patients could benefit from treatment for panic disorder.
Subject(s)
Chest Pain/diagnostic imaging , Coronary Angiography , Family , Panic Disorder/diagnosis , Alcoholism/diagnosis , Alcoholism/genetics , Chest Pain/diagnosis , Chest Pain/therapy , Depressive Disorder/diagnosis , Depressive Disorder/genetics , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Male , Middle Aged , Panic Disorder/genetics , Panic Disorder/therapy , Psychiatric Status Rating ScalesABSTRACT
OBJECTIVE: Nonfearful panic disorder meets the DSM-III-R criteria for panic disorder but is not associated with subjective fear and anxiety. The authors determined its prevalence in a group of neurology patients and assessed its diagnostic validity as a panic disorder subtype by evaluating the response of the patients with nonfearful panic disorder to sodium lactate and antipanic pharmacotherapy. METHOD: The subjects were all neurology patients referred over 1 year to a university hospital's psychiatric consultation service because of negative medical workups for their symptoms (N = 48). Patients who met the DSM-III-R criteria for panic disorder but did not report subjective anxiety or fear during panic episodes were diagnosed as having nonfearful panic disorder. Afterward, each of those patients received a sodium lactate infusion and, 5 hours later, a sodium chloride infusion. They were then treated with antipanic medication and followed for at least 6 months. RESULTS: Of the 48 neurology patients referred for psychiatric evaluation, 11 (23%) met the criteria for panic disorder, and all 11 met the criteria for nonfearful panic disorder. All 11 responded positively to lactate but not to placebo, and they each experienced an at least 75% reduction in symptoms during the 6-month follow-up period. Detailed case reports of three of these patients are presented. CONCLUSIONS: These findings support the construct and predictive diagnostic validity of nonfearful panic disorder as a subtype of panic disorder and suggest that a lack of attention to this group leads to both the underestimation of the prevalence of panic disorder and to the withholding of potentially successful treatments for this group.
