Vasoactive intestinal peptide (VIP) conveys various physiological effects in the digestive tract, nervous and cardiovascular system, airways, reproductive system, endocrine system, and more. A family of specific membrane bound receptors, termed VPAC1, VPAC2, and PAC1, bind VIP and trigger the effects. Many of them are of clinical interest. To date more than two thousand publications suggest the use of VIP in diseases like asthma, erectile dysfunction, blood pressure regulation, inflammation, endocrinology, tumours, etc. Despite this considerable potential, the peptide is not regularly used in clinical settings. A key problem is the short half life of inhaled or systemically administered VIP due to rapid enzymatic degradation. This shortcomings could be overcome with stable derivates or improved pharmacokinetics. A promising strategy is to use biocompatible and degradable depots, to protect the peptide from early degradation and allow for controlled release. This review focuses on aspects of clinical applications of VIP and the idea to use formulations based on biodegradable particles, to constitute a dispersible VIP-depot. Smart particle systems protect the peptide from early degradation, and assist the sustainable cell targeting with VIP for therapeutic or imaging purposes.
Abstract Neutrophil azurophil granules, traditionally regarded as the neutrophil counterpart to lysosomes, lack the lysosomal marker lysosome-associated membrane glycoprotein and have recently been suggested to be nonlysosomal secretory organelles. The membrane of the azurophil granules is poorly characterized—CD63 and CD68 are the only membrane proteins identified so far. Here, azurophil granule membranes were isolated by Percoll gradient subcellular fractionation. Using matrix-assisted laser desorption ionization time of flight mass spectrometry of tryptic peptides from an isolated protein, stomatin was identified in these membranes. Using immunoelectron microscopy and immunoblot analysis of isolated organelles, stomatin was found to be subcellularly localized, not only to the azurophil granules but also by a major part to the specific granules and by a minor part to the secretory vesicles/plasma membrane. We also show the presence of detergent-insoluble, low-density membrane domains in the plasma membrane and the granule membranes and found stomatin to be localized to these domains.
The new data presented by the participants during the 'Colloquium on the Nucleolus' were reviewed and regrouped in different topics concerning the molecular and functional significance of nucleolar structure. The topics included: rRNA transcription and nucleolar organization, the nucleolus in relation to cell proliferation including nucleolus in pathology during the cell cycle and cell division, nucleologenesis, and nucleolar proteins.
Primary pulmonary hypertension is a fatal disease causing progressive right heart failure within 3 years after diagnosis. We describe a new concept for treatment of the disease using vasoactive intestinal peptide, a neuropeptide primarily functioning as a neurotransmitter that acts as a potent systemic and pulmonary vasodilator. Our rationale is based on the finding of a deficiency of the peptide in serum and lung tissue of patients with primary pulmonary hypertension, as evidenced by radioimmunoassay and immunohistochemistry. The relevance of this finding is underlined by an upregulation of corresponding receptor sites as shown by Northern blot analysis, Western blot analysis, and immunological techniques. Consequently, the substitution with the hormone results in substantial improvement of hemodynamic and prognostic parameters of the disease without side effects. It decreased the mean pulmonary artery pressure in our eight study patients, increased cardiac output, and mixed venous oxygen saturation. Our data provide enough proof for further investigation of vasoactive intestinal peptide and its role in primary pulmonary hypertension.
Abstract In clinical practice, the treatment of patients with irritable bowel syndrome (IBS) can be very challenging. The aims of the present non-interventional study (NIS) were to investigate the tolerability and efficacy of PMA-zeolite under everyday conditions in patients with diarrheic IBS type (IBS-D) or constipated type (IBS-C) or mixed type (IBS-M). Methods To document prospective data on tolerability and symptom frequency in the frame of a nationwide NIS, we recruited 204 IBS patients. The study focused on the IBS-related quality of life (measured by the SF-36 questionnaire) and improvements of IBS-related symptoms according to specific ROM-III criteria and stool consistency (Bristol stool scale). The participants documented their abdominal pain, bloating, number of bowel movements, and stool consistency through a web-based internet platform (initial and exit questionnaires) and daily diary entries over the period of intake (8 weeks). Results A total of 82.2% of the recruited patients had filled in the questionnaires before and after the 8-week treatment with PMA-zeolite. Seven of the eight subscales of the SF-36 improved significantly (p<0,001); the reduction in abdominal pain was especially significant (p<0,001). The diary entries confirmed the reduction in abdominal pain and revealed a significant reduction in days with bloating (p<0,001). The Bristol-stool-scale analysis showed improvements; particularly, patients with IBS-D benefited from the treatment (p<0,001). Conclusion The treatment duration of 8 weeks was well tolerated by most patients. Under everyday life conditions, PMA-zeolite alleviated the global IBS-related symptoms and raised the quality of life (QOL). The PMA-zeolite, thus, may represent a good adjuvant therapeutic option for patients with irritable bowel syndrome.
Cleft Lip and Palate (CLP) - a common facial malformation in newborns - is typically corrected by surgical intervention to allow for normal speech development, psychosocial adjustment, and facial attractiveness. The long term treatment outcome can be evaluated after a number of years, possibly in adulthood. We investigated the aesthetics of the nasolabial region by subjective ratings. To compare various surgical approaches we recruited 12 raters to evaluate 429 patients. Expert and lay raters judged photographs from patients, who have completed treatment with one of three different surgical strategies performed in our institution over 50 years. Facial photographs were cropped, presented to the raters in a randomized sequence, and judged by the raters on a 5 point Likert scale. The subjective ratings between the raters revealed a fair to substantial inter-rater reliability. The average ratings of the surgical outcome improved continuously over the investigated 5 decades. Despite possible differences between raters and rater groups this overall result was consistently seen in the gender groups (male/female), or expertise related groups (expert/lay). Our analysis revealed that patients with bilateral CLP scored worse than patients with unilateral CLP when treated in the fifties; more recently treated patients of both groups scored similarly.
