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- Hanner, Per, 1948, et al.
(author)
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Antisecretory factor-inducing therapy improves the clinical outcome in patients with Meniere's disease
- 2010
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In: Acta Oto-Laryngologica. - : Informa UK Limited. - 0001-6489 .- 1651-2251. ; 130:2, s. 223-227
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Journal article (peer-reviewed)abstract
- Conclusion: Intake of antisecretory factor (AF)-inducing SPC-flakes (R) significantly reduced vertigo in patients suffering from Meniere's disease (MD). The positive effect may be due to a modulation of the transport of water and ions in the endolymphatic space. Objective: To evaluate the effects of a 3-month treatment period with SPC-flakes (R) in patients suffering from MD. Patients and methods: A prospective, double-blind, placebo-controlled study was performed. A total of 51 adult patients with MD were included in the study: 27 subjects treated with SPC-flakes (R) and 24 subjects with control cereals. The patients received SPC-flakes (R) or control cereals (I g per kg body weight per 24 h in two servings) for 3 months. Otoneurological examinations were carried out before and after this period. Results: The severity of MD was classified according to the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) grading system. Fourteen of the 27 patients randomized to intake of the AF-inducing SPC-flakes (R) reported decreased vertigo, compared with 2 of 24 in the control group (p < 0.001). No consistent change in the otoneurological examinations could be demonstrated in any of the groups of patients.
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- Abel, Edvard, 1970, et al.
(author)
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Early disturbance of microvascular function precedes chemotherapy-induced intestinal injury
- 2005
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In: Dig Dis Sci. - : Springer Science and Business Media LLC. - 0163-2116. ; 50:9, s. 1729-33
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Journal article (peer-reviewed)abstract
- Intestinal injury 4-48 hr after cytotoxic therapy (etoposide phosphate, 100 mg/kg body weight [bw], intravenously [i.v.]) was studied in rats using ligated intestinal loops. Chromium-51 ethylenediaminetetraacetic acid ((51)Cr-EDTA) and rubidium-86 chloride ((86)RbCl) were deposited intraluminally to determine the extent of the increase in intestinal permeability and ion channel disruption. Evans Blue (EB) was used for detection of endothelial leakage. Intestinal morphology was documented. Endothelial dysfunction, as observed by an increased extravasation of EB, was evident already 4 hr after cytotoxic therapy. Intestinal epithelial injury, as observed by an increase in (51)Cr-EDTA permeation and a decrease in (86)Rb absorption, occurred after 48 hr. Finally, histology disclosed a reduced crypt cell proliferation, displayed as a decrease in Ki67-positive cells. The findings suggest that, in the development of intestinal injury after cytotoxic therapy, endothelial disruption is an early event, whereafter epithelial dysfunction and crypt stem cell arrest occur. This knowledge could be of importance in the design of future intervention trials.
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- Al-Olama, Mohamed, et al.
(author)
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The peptide AF-16 decreases high interstitial fluid pressure in solid tumors.
- 2011
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In: Acta oncologica (Stockholm, Sweden). - 1651-226X.
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Journal article (peer-reviewed)abstract
- Abstract Background. The high interstitial fluid pressure (IFP) in solid tumors restricts the access to nutrients, oxygen and drugs. Material and methods. We investigated the ability of the peptide AF-16, involved in water and ion transfer through cell membranes, to lower the IFP in two different solid rat mammary tumors, one chemically induced, slowly growing, and the other transplantable, and rapidly progressing having high cellularity. AF-16 was administered either in the tumor capsule, intranasally or intravenously. The IFP was measured by a miniature fiber optic device. Results. AF-16 significantly lowered the IFP in both the slowly and the rapidly progressing tumors, whether administrated locally or systemically. The AF-16 induced IFP reduction was maximal after 90 min, lasted at least 3 h, and returned to pretreatment levels in less than 24 h. Topical AF-16 transiently reduced the IFP in the DMBA tumors from 17.7 ± 4.2 mmHg to 8.6 ± 2.1 mmHg. Conclusion. We conclude that AF-16 transiently and reversibly lowered the high IFP in solid tumors during a few hours, which might translate into improved therapeutic efficacy.
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| 7. |
- Al-Olama, Mohamed, et al.
(author)
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Uptake of the antisecretory factor peptide AF-16 in rat blood and cerebrospinal fluid and effects on elevated intracranial pressure
- 2015
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In: Acta Neurochirurgica. - : Springer Science and Business Media LLC. - 0001-6268 .- 0942-0940. ; 157:1, s. 129-137
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Journal article (peer-reviewed)abstract
- AF-16 is a 16-amino-acid-long peptide derived from the amino-terminal part of the endogenous protein, antisecretory factor (AF). AF-16 in vivo has been shown to regulate dysfunctions in the water and ion transport system under various pathological conditions and also to counteract experimentally increased tissue pressure. Rats were subjected to a cryogenic brain injury in order to increase the intracranial pressure (ICP). The distribution of AF-16 in blood and CSF after intravenous or intranasal administration was determined in injured and control rats. ICP was monitored in freely moving, awake rats, by means of an epidural pressure transducer catheter connected to a wireless device placed subcutaneously on the skull. The continuous ICP registrations were achieved by means of telemetry. Intranasal administration of AF-16 resulted in a significantly higher CSF concentrations of AF-16 in injured than in control rats, 1.3 versus 0.6 ng/ml, whereas no difference between injured and control rats was seen when AF-16 was given intravenously. Rats subjected to cryogenic brain injury developed gradually increasing ICP levels. Intranasal administration of AF-16 suppressed the increased ICP to normal values within 30 min. Optimal AF-16 concentrations in CSF are achieved after intranasal administration in rats subjected to a cryogenic brain injury. The ability of AF-16 to suppress an increased ICP was manifested.
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| 8. |
- Bazzurro, V., et al.
(author)
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Antisecretory Factor Modulates GABAA Receptor Activity in Neurons
- 2018
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In: Journal of Molecular Neuroscience. - : Springer Science and Business Media LLC. - 0895-8696 .- 1559-1166. ; 64:2, s. 312-320
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Journal article (peer-reviewed)abstract
- The antisecretory factor is an endogenous protein found in all mammalian tissues investigated so far. It acts by counteracting intestinal hypersecretion and various forms of inflammation, but the detailed mechanism of antisecretory factor (AF) action is unknown. We tested neuronal GABAA receptors by means of AF-16, a potent AF peptide derived from amino acids 36–51 from the NH2 part of AF. Cultured rat cerebellar granule cells were used, and the effects on the GABA-mediated chloride currents were determined by whole-cell patch clamp. Both the neurotransmitter GABA and AF-16 were added by perfusion of the experimental system. A 3-min AF-16 preincubation was more efficacious than 30s in significantly elevating the rapidly desensitizing GABA-activated chloride current. No effect was found on the tonic, slowly desensitizing current. The GABA-activated current increase by AF-16 demonstrated a low k of 41pM with a maximal increase of 37% persisting for some minutes after AF washout, independent from GABA concentration. This indicates an effect on the maximal stimulation (E%Max) excluding an altered affinity between GABA and its receptor. An immunocytochemical fluorescence approach with anti γ2 subunit antibodies demonstrated an increased expression of GABAA receptors. Thus, both the electrophysiological and the immunofluorescence approach indicate an increased appearance of GABAA receptors on the neuronal membrane. The rationale of the experiments was to test the effect of AF on a defined neuronal population of GABAA receptors. The implications of the results on the impact of AF on the enteric nervous system or on brain function are discussed. © 2018, Springer Science+Business Media, LLC, part of Springer Nature.
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| 9. |
- Bazzurro, V., et al.
(author)
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Involvement of GABA(A) receptors containing alpha(6) subtypes in antisecretory factor activity on rat cerebellar granule cells studied by two-photon uncaging
- 2022
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In: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568. ; 56:5, s. 4505-4513
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Journal article (peer-reviewed)abstract
- The antisecretory factor (AF) is an endogenous protein that counteracts intestinal hypersecretion and various inflammation conditions in vivo. It has been detected in many mammalian tissues and plasma, but its mechanisms of action are largely unknown. To study the pharmacological action of the AF on different GABA(A) receptor populations in cerebellar granule cells, we took advantage of the two-photon uncaging method as this technique allows to stimulate the cell locally in well-identified plasma membrane parts. We compared the electrophysiological response evoked by releasing a caged GABA compound on the soma, the axon initial segment and neurites before and after administering AF-16, a 16 amino acids long peptide obtained from the amino-terminal end of the AF protein. After the treatment with AF-16, we observed peak current increases of varying magnitude depending on the neuronal region. Thus, studying the effects of furosemide and AF-16 on the electrophysiological behaviour of cerebellar granules, we suggest that GABA(A) receptors, containing the alpha(6) subunit, may be specifically involved in the increase of the peak current by AF, and different receptor subtype distribution may be responsible for differences in this increase on the cell.
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