Enzymatic antioxidant system in the cestode Hymenolepis diminuta after chronic infection of the rat

Background

The aim of the present paper was to describe the enzymatic antioxidant system in Hymenolepis diminuta collected from rats exposed to chronic cestode invasion.

Methodology

We dissected different tissues of H. diminuta (immature proglottids, genital primordia, hermaphroditic proglottids, early uterus, and gravid uterus) and studied activity of: superoxide dismutases (SOD1 and SOD2), catalase (CAT), glutathione peroxidases (non-Se-dependent GSHPx and Se-dependent GSHPx), glutathione-S-transferase (GST) and glutathione reductase (GSHR), and oxidative stress markers ?? reduced glutathione (GSH), and the lipid peroxidation level (TBARS).

Results

We demonstrated changes in antioxidant enzyme activities and levels of oxidative stress markers in different tissues of the parasite. The levels of TBARS and GSH indicate that oxidative stress occurred in tissues located proximal to the intestine wall. Activity of SOD1 was high in all parts of H. diminuta, but the GST activity was the highest of all studied antioxidant enzymes. SOD2 activity differed significantly in various parts of H. diminuta. Significant differences were observed for nonSeGSHPx and activity of other GSH-dependent enzymes was generally similar in all the tissues.

Conclusions

Our results show that the enzymatic antioxidant system of H. diminuta, allows the parasite to adapt and live under conditions of chronic oxidative stress. It suggests an oxidative-antioxidative balance during interactions between parasite and host.     

Sendai virus-based liposomes enable targeted cytosolic delivery of nanoparticles in brain tumor-derived cells

Background

Nanogold has been investigated in a wide variety of biomedical applications because of the anti-inflammatory properties. The purpose of this study was to evaluate the effects of TPU (Therapeutic Pulsed Ultrasound) with gold nanoparticles (GNP) on oxidative stress parameters and the expression of pro-inflammatory molecules after traumatic muscle injury.

Materials and methods

Animals were divided in nine groups: sham (uninjured muscle); muscle injury without treatment; muscle injury + DMSO; muscle injury + GNP; muscle injury + DMSO + GNP; muscle injury + TPU; muscle injury + TPU + DMSO; muscle injury + TPU + GNP; muscle injury + TPU + DMSO + GNP. The ROS production was determined by concentration of superoxide anion, modulation of antioxidant defenses was determined by the activity of superoxide dismutase, catalase and glutathione peroxidase enzymes, oxidative damage determined by formation of thiobarbituric acid-reactive substance and protein carbonyls. The levels of interleukin-1?? (IL-1??) and tumor necrosis factor-?? (TNF-??) were measured as inflammatory parameters.

Results

Compared to muscle injury without treatment group, the muscle injury + TPU + DMSO + GNP gel group promoted a significant decrease in superoxide anion production and lipid peroxidation levels (p < 0.050). It also showed a significant decrease in TNF-?? and IL-1?? levels (p < 0.050) when compared to muscle injury without treatment group.

Conclusions

Our results suggest that TPU + DMSO + GNP gel presents beneficial effects on the muscular healing process, inducing a reduction in the production of ROS and also the expression of pro-inflammatory molecules.     

Anaphylactic Reactions to Oligosaccharides in Red Meat: a Syndrome in Evolution

Background

Human mast cells are capable of a wide variety of inflammatory responses and play a vital role in the pathogenesis of inflammatory diseases such as allergy, asthma, and atherosclerosis. We have reported that cigarette smoke extract (CSE) significantly increased IL-6 and IL-8 production in IL-1??-activated human mast cell line (HMC-1). Baicalein (BAI) has anti-inflammatory properties and inhibits IL-1??- and TNF-??-induced inflammatory cytokine production from HMC-1. The goal of the present study was to examine the effect of BAI on IL-6 and IL-8 production from CSE-treated and IL-1??-activated HMC-1.

Methods

Main-stream (Ms) and Side-stream (Ss) cigarette smoke were collected onto fiber filters and extracted in RPMI-1640 medium. Two ml of HMC-1 at 1 × 10⁶ cells/mL were cultured with CSE in the presence or absence of IL-1?? (10 ng/mL) for 24 hrs. A group of HMC-1 cells stimulated with both IL-1?? (10 ng/ml) and CSE was also treated with BAI. The expression of IL-6 and IL-8 was assessed by ELISA and RT-PCR. NF-??B activation was measured by electrophoretic mobility shift assay (EMSA) and I??B?? degradation by Western blot.

Results

Both Ms and Ss CSE significantly increased IL-6 and IL-8 production (p < 0.001) in IL-1??-activated HMC-1. CSE increased NF-??B activation and decreased cytoplasmic I??B?? proteins in IL-1??-activated HMC-1. BAI (1.8 to 30 ??M) significantly inhibited production of IL-6 and IL-8 in a dose-dependent manner in IL-1??-activated HMC-1 with the optimal inhibition concentration at 30 ??M, which also significantly inhibited the enhancing effect of CSE on IL-6 and IL-8 production in IL-1??-activated HMC-1. BAI inhibited NF-??B activation and increased cytoplasmic I??B?? proteins in CSE-treated and IL-1??-activated HMC-1.

Conclusions

Our results showed that CSE significantly increased inflammatory cytokines IL-6 and IL-8 production in IL-1??-activated HMC-1. It may partially explain why cigarette smoke contributes to lung and cardiovascular diseases. BAI inhibited the production of inflammatory cytokines through inhibition of NF-??B activation and I??B?? phosphorylation and degradation. This inhibitory effect of BAI on the expression of inflammatory cytokines induced by CSE suggests its usefulness in the development of novel anti-inflammatory therapies.     

Cryptococcus neoformans induces IL-8 secretion and CXCL1 expression by human bronchial epithelial cells

Background

Smoking is the most important cause for the development of COPD. Since not all smokers develop COPD, it is obvious that other factors must be involved in disease development. We hypothesize that heme oxygenase-1 (HO-1), a protective enzyme against oxidative stress and inflammation, is insufficiently upregulated in COPD. The effects of HO-1 modulation on cigarette smoke induced inflammation and emphysema were tested in a smoking mouse model.

Methods

Mice were either exposed or sham exposed to cigarette smoke exposure for 20 weeks. Cobalt protoporphyrin or tin protoporphyrin was injected during this period to induce or inhibit HO-1 activity, respectively. Afterwards, emphysema development, levels of inflammatory cells and cytokines, and the presence of B-cell infiltrates in lung tissue were analyzed.

Results

Smoke exposure induced emphysema and increased the numbers of inflammatory cells and numbers of B-cell infiltrates, as well as the levels of inflammatory cytokines in lung tissue. HO-1 modulation had no effects on smoke induced emphysema development, or the increases in neutrophils and macrophages and inflammatory cytokines. Interestingly, HO-1 induction prevented the development of smoke induced B-cell infiltrates and increased the levels of CD4⁺CD25⁺ T cells and Foxp3 positive cells in the lungs. Additionally, the CD4⁺CD25⁺ T cells correlated positively with the number of Foxp3 positive cells in lung tissue, indicating that these cells were regulatory T cells.

Conclusion

These results support the concept that HO-1 expression influences regulatory T cells and indicates that this mechanism is involved in the suppression of smoke induced B-cell infiltrates. The translation of this interaction to human COPD should now be pursued.     

Analyse du statut oxydatif spermatique chez des patients infertiles

Introduction

Male infertility constitutes public health problems. Several factors are at the origin of this phenomenon. Currently, the oxidative stress is accused to be one of the leading causes. In our study, we sought a correlation between the markers of the oxidative stress and the sperm characteristics (morphology).

Material and methods

We evaluated the antioxidant status in the seminal plasma of 129 infertile men. Patients were characterized by infertility of variable duration. They were divided into four groups: normozoospermics who were considered as controls (n=34), asthenozoospermics (Astheno; n=43), oligozoospermics (Oligo; n=22) and teratozoospermics (Terato; n=30). Among the oxidative stress markers, we evaluated, in seminal plasma, zinc, calcium, magnesium and selenium by spectrophotometry of atomic absorption to flame and furnace. The malondialdehyde (MDA) is proportioned by spectrofluorometry.

Results

Our results show that the seminal concentrations of zinc and selenium are higher in the control group than the concentrations of these same elements in the three other groups. The seminal zinc concentration was significantly correlated with the sperm count (r=0.49; p < 0.001) and MDA (r=- 0.35; p<0.05). Sperm motility was correlated with calcium (r=0.41; p<0.001) and magnesium (r=0.31; p<0.05). The MDA concentration is higher in the three groups of patients: oligozoospermics (3.22±1.37 ??g/ml), asthenozoospermics (3.52±1.93 ??g/ml) and teratozoospermics (3.64±1.73 ??g/ml) compared with controls (2.32±0.94 ??g/ml). A single positive correlation was observed between the MDA and morphology (r=0.19; p<0.05).

Conclusion

Our study confirms that the oxidative stress plays an important role in the process of deteriorations of the spermatozoa. The free radicals can, indeed, modify the membrane structure as well as the membrane structure of the deoxyribonucleic acid. These deteriorations also lead to an increase in the percentage of sperm of abnormal forms.     

IL-3 and TNFα increase Thymic Stromal Lymphopoietin Receptor (TSLPR) expression on eosinophils and enhance TSLP-stimulated degranulation

Background

Thymic stromal lymphopoietin (TSLP) and eosinophils are prominent components of allergic inflammation. Therefore, we sought to determine whether TSLP could activate eosinophils, focusing on measuring the regulation of TSLPR expression on eosinophils and degranulation in response to TSLP, as well as other eosinophil activation responses.

Methods

Eosinophil mRNA expression of TSLPR and IL-7R?? was examined by real-time quantitative PCR of human eosinophils treated with TNF?? and IL-5 family cytokines, and TSLPR surface expression on eosinophils was analyzed by flow cytometry. Eosinophils were stimulated with TSLP (with and without pre-activation with TNF?? and IL-3) and evaluated for release of eosinophil derived neurotoxin (EDN), phosphorylation of STAT5, and survival by trypan blue exclusion. A blocking antibody for TSLPR was used to confirm the specificity of TSLP mediated signaling on eosinophil degranulation.

Results

Eosinophil expression of cell surface TSLPR and TSLPR mRNA was upregulated by stimulation with TNF?? and IL-3. TSLP stimulation resulted in release of EDN, phosphorylation of STAT5 as well as promotion of viability and survival. TSLP-stimulated eosinophil degranulation was inhibited by a functional blocking antibody to TSLPR. Pre-activation of eosinophils with TNF?? and IL-3 promoted eosinophil degranulation at lower concentrations of TSLP stimulation.

Conclusions

This study demonstrates that eosinophils are activated by TSLP and that eosinophil degranulation in response to TSLP may be enhanced on exposure to cytokines present in allergic inflammation, indicating that the eosinophil has the capacity to participate in TSLP-driven allergic responses.     

BMPR2 expression is suppressed by signaling through the estrogen receptor

Background

Low endogenous testosterone levels have been shown to be a risk factor for the development of cardiovascular disease and cardiovascular benefits associated with testosterone replacement therapy are being advocated; however, the effects of endogenous testosterone levels on acute coronary vasomotor responses to androgen administration are not clear. The objective of this study was to compare the effects of acute androgen administration on in vivo coronary conductance and in vitro coronary microvascular diameter in intact and castrated male swine.

Methods

Pigs received intracoronary infusions of physiologic levels (1?C100 nM) of testosterone, the metabolite 5??-dihydrotestosterone, and the epimer epitestosterone while left anterior descending coronary blood flow and mean arterial pressure were continuously monitored. Following sacrifice, coronary arterioles were isolated, cannulated, and exposed to physiologic concentrations (1?C100 nM) of testosterone, 5??-dihydrotestosterone, and epitestosterone. To evaluate effects of the androgen receptor on acute androgen dilation responses, real-time PCR and immunohistochemistry for androgen receptor were performed on conduit and resistance coronary vessels.

Results

In vivo, testosterone and 5??-dihydrotestosterone produced greater increases in coronary conductance in the intact compared to the castrated males. In vitro, percent maximal dilation of microvessels was similar between intact and castrated males for testosterone and 5??-dihydrotestosterone. In both studies epitestosterone produced significant increases in conductance and microvessel diameter from baseline in the intact males. Androgen receptor mRNA expression and immunohistochemical staining were similar in intact and castrated males.

Conclusions

Acute coronary vascular responses to exogenous androgen administration are increased by endogenous testosterone, an effect unrelated to changes in androgen receptor expression.     

Generation and characterization of transgenic mice expressing mitochondrial targeted red fluorescent protein selectively in neurons: modeling mitochondriopathy in excitotoxicity and amyotrophic lateral sclerosis

Background

Accumulation of aberrant proteins to form Lewy bodies (LBs) is a hallmark of Parkinson's disease (PD). Ubiquitination-mediated degradation of aberrant, misfolded proteins is critical for maintaining normal cell function. Emerging evidence suggests that oxidative/nitrosative stress compromises the precisely-regulated network of ubiquitination in PD, particularly affecting parkin E3 ligase activity, and contributes to the accumulation of toxic proteins and neuronal cell death.

Results

To gain insight into the mechanism whereby cell stress alters parkin-mediated ubiquitination and LB formation, we investigated the effect of oxidative stress. We found significant increases in oxidation (sulfonation) and subsequent aggregation of parkin in SH-SY5Y cells exposed to the mitochondrial complex I inhibitor 1-methyl-4-phenlypyridinium (MPP ⁺ ), representing an in vitro cell-based PD model. Exposure of these cells to direct oxidation via pathological doses of H₂O₂ induced a vicious cycle of increased followed by decreased parkin E3 ligase activity, similar to that previously reported following S-nitrosylation of parkin. Pre-incubation with catalase attenuated H₂O₂ accumulation, parkin sulfonation, and parkin aggregation. Mass spectrometry (MS) analysis revealed that H₂O₂ reacted with specific cysteine residues of parkin, resulting in sulfination/sulfonation in regions of the protein similar to those affected by parkin mutations in hereditary forms of PD. Immunohistochemistry or gel electrophoresis revealed an increase in aggregated parkin in rats and primates exposed to mitochondrial complex I inhibitors, as well as in postmortem human brain from patients with PD with LBs.

Conclusion

These findings show that oxidative stress alters parkin E3 ligase activity, leading to dysfunction of the ubiquitin-proteasome system and potentially contributing to LB formation.     

Transient pharmacologic lowering of Aβ production prior to deposition results in sustained reduction of amyloid plaque pathology

Background

Alzheimer??s disease (AD) is the leading cause of dementia among the elderly. Disease modifying therapies targeting A?? that are in development have been proposed to be more effective if treatment was initiated prior to significant accumulation of A?? in the brain, but optimal timing of treatment initiation has not been clearly established in the clinic. We compared the efficacy of transient pharmacologic reduction of brain A?? with a ??-secretase inhibitor (GSI ) for 1?C3?months (M) treatment windows in APP Tg2576 mice and subsequent aging of the mice to either 15M or 18M.

Results

These data show that reducing A?? production in a 2-3M windows both initiated and discontinued before detectable A?? deposition has the most significant impact on A?? loads up to 11M after treatment discontinuation. In contrast, initiation of treatment for 3M windows from 7-10M or 12-15M shows progressively decreasing efficacy.

Conclusions

These data have major implications for clinical testing of therapeutics aimed at lowering A?? production, indicating that; i) these therapies may have little efficacy unless tested as prophylactics or in the earliest preclinical stage of AD where there is no or minimal A?? accumulation and ii) lowering A?? production transiently during a critical pre-deposition window potentially provides long-lasting efficacy after discontinuation of the treatment.     

Invulnerability of bromelain against oxidative degeneration and cholinergic deficits imposed by dichlorvos in mice brains

Background

The present study elucidates the protective potential of bromelain against dichlorvos intoxication in mice brains. Dichlorvos induces the oxidative stress by disproportionating the balance between free radicals generation and their scavenging in neurons which leads to neuronal degeneration.

Methods

In this study, mice were divided into four groups-group I (control), group II (dichlorvos treated), group III (bromelain treated) and group IV (exposed to both bromelain and dichlorvos both).

Results

Dichlorvos treatment increased the levels of thiobarbituric acid reactive substances (TBARS) and protein carbonyl content (PCC) which indicate the increased oxidative stress. Meanwhile, brain endogenous antioxidants and cholinesterases level was decreased after dichlorvos exposure. Levels of TBARS and PCC decreased whereas cholinesterases level was recorded to be elevated after bromelain exposure.

Conclusion

Bromelain offered neuroprotection by decreasing oxidative stress and augmenting cholinesterases in mice brains. This study highlights the invulnerability of bromelain against oxidative and cholinergic deficits in mice brains.

     

A phase I study evaluating the pharmacokinetics, safety and tolerability of an antibody-based tissue factor antagonist in subjects with acute lung injury or acute respiratory distress syndrome

Background

Several studies suggest an increase of oxidative stress and a reduction of endothelial function in obstructive sleep apnoea syndrome (OSAS). We assessed the association between OSAS, endothelial dysfunction and oxidative stress. Further aim was to evaluate the effect of nasal continuous positive airway pressure (nCPAP) on oxidative stress and arterial dysfunction.

Methods

We studied 138 consecutive patients with heavy snoring and possible OSAS. Patients underwent unattended overnight home polysomnography. Ten patients with severe OSAS were revaluated after 6?months of nCPAP therapy. To assess oxidative stress in vivo, we measured urinary 8-iso-PGF2?? and serum levels of soluble NOX2-derived peptide (sNOX2-dp). Serum levels of nitrite/nitrate (NOx) were also determined. Flow-mediated brachial artery dilation (FMD) was measured to asses endothelial function.

Results

Patients with severe OSAS had higher urinary 8-iso-PGF2?? (p<0.001) and serum NOX2 and lower NOx. A negative association was observed between FMD and OSA severity. Apnea/hypopnea index was significantly correlated with the indices of central obesity and with urinary 8-isoprostanes (r=0.298, p<0.001). The metabolic syndrome (t=-4.63, p<0.001) and urinary 8-isoprostanes (t=-2.02, p<0.05) were the only independent predictors of FMD. After 6-months nCPAP treatment, a significant decrease of serum NOX2, (p<0.005) and urinary 8-iso-PGF2?? (p<0.01) was observed, while serum NOx showed only a minor increase. A statistically significant increase of FMD was observed (from 3.6% to 7.0%).

Conclusions

The results of our study indicate that patients with OSAS and cardiometabolic comorbidities have increased oxidative stress and arterial dysfunction that are partially reversed by nCPAP treatment.     

Characterization of the antiproliferative activity of Xylopia aethiopica

Background

Xylopia aethiopica, a plant found throughout West Africa, has both nutritional and medicinal uses. The present study aims to characterize the effects of extracts of this plant on cancer cells.

Results

We report that X. aethiopica extract prepared with 70% ethanol has antiproliferative activity against a panel of cancer cell lines. The IC50 was estimated at 12 ??g/ml against HCT116 colon cancer cells, 7.5 ??g/ml and > 25 ??g/ml against U937 and KG1a leukemia cells, respectively. Upon fractionation of the extract by HPLC, the active fraction induced DNA damage, cell cycle arrest in G1 phase and apoptotic cell death. By using NMR and mass spectrometry, we determined the structure of the active natural product in the HPLC fraction as ent-15-oxokaur-16-en-19-oic acid.

Conclusion

The main cytotoxic and DNA-damaging compound in ethanolic extracts of Xylopia aethiopica is ent-15-oxokaur-16-en-19-oic acid.     

Validation of the theoretical domains framework for use in behaviour change and implementation research

Background

An integrative theoretical framework, developed for cross-disciplinary implementation and other behaviour change research, has been applied across a wide range of clinical situations. This study tests the validity of this framework.

Methods

Validity was investigated by behavioural experts sorting 112 unique theoretical constructs using closed and open sort tasks. The extent of replication was tested by Discriminant Content Validation and Fuzzy Cluster Analysis.

Results

There was good support for a refinement of the framework comprising 14 domains of theoretical constructs (average silhouette value 0.29): ??Knowledge??, ??Skills??, ??Social/Professional Role and Identity??, ??Beliefs about Capabilities??, ??Optimism??, ??Beliefs about Consequences??, ??Reinforcement??, ??Intentions??, ??Goals??, ??Memory, Attention and Decision Processes??, ??Environmental Context and Resources??, ??Social Influences??, ??Emotions??, and ??Behavioural Regulation??.

Conclusions

The refined Theoretical Domains Framework has a strengthened empirical base and provides a method for theoretically assessing implementation problems, as well as professional and other health-related behaviours as a basis for intervention development.     

The level of hypotension during hemorrhagic shock is a major determinant of the post-resuscitation systemic inflammatory response: an experimental study

Background

To evaluate whether the level of hypotension during hemorrhagic shock may influence the oxidative and inflammatory responses developed during post-ischemic resuscitation.

Methods

Fifteen rabbits were equally allocated into three groups: sham-operated (group sham); bled within 30 minutes to mean arterial pressure (MAP) of 40 mmHg (group shock-40); bled within 30 minutes to MAP of 30 mmHg (group shock-30). Shock was maintained for 60 min. Resuscitation was performed by reinfusing shed blood with two volumes of Ringer's lactate and blood was sampled for estimation of serum levels aminotransferases, creatinine, TNF-α, IL-1β, IL-6, malondialdehyde (MDA) and total antioxidant status (TAS) and for the determination of oxidative burst of polymorhonuclears (PMNs) and mononuclear cells (MCs).

Results

Serum AST of group shock-30 was higher than that of group shock-40 at 60 and 120 minutes after start of resuscitation; serum creatinine of group shock-30 was higher than group shock-40 at 120 minutes. Measured cytokines, MDA and cellular oxidative burst of groups, shock-40 and shock-30 were higher than group sham within the first 60 minutes after start of resuscitation. Serum concentrations of IL-1β, IL-6 and TNF-α of group shock-30 were higher than group shock-40 at 120 minutes (p < 0.05). No differences were found between two groups regarding serum MDA and TAS and oxidative burst on PMNs and MCs but both groups were different to group sham.

Conclusion

The level of hypotension is a major determinant of the severity of hepatic and renal dysfunction and of the inflammatory response arising during post-ischemic hemorrhagic shock resuscitation. These findings deserve further evaluation in the clinical setting.     

Structural and mechanistic investigations on Salmonella typhimurium acetate kinase (AckA): identification of a putative ligand binding pocket at the dimeric interface

Background

A large number of studies have been carried out to obtain amino acid propensities for ??-helices and ??-sheets. The obtained propensities for ??-helices are consistent with each other, and the pair-wise correlation coefficient is frequently high. On the other hand, the ??-sheet propensities obtained by several studies differed significantly, indicating that the context significantly affects ??-sheet propensity.

Results

We calculated amino acid propensities for ??-helices and ??-sheets for 39 and 24 protein folds, respectively, and addressed whether they correlate with the fold. The propensities were also calculated for exposed and buried sites, respectively. Results showed that ??-helix propensities do not differ significantly by fold, but ??-sheet propensities are diverse and depend on the fold. The propensities calculated for exposed sites and buried sites are similar for ??-helix, but such is not the case for the ??-sheet propensities. We also found some fold dependence on amino acid frequency in ??-strands. Folds with a high Ser, Thr and Asn content at exposed sites in ??-strands tend to have a low Leu, Ile, Glu, Lys and Arg content (correlation coefficient = ?0.90) and to have flat ??-sheets. At buried sites in ??-strands, the content of Tyr, Trp, Gln and Ser correlates negatively with the content of Val, Ile and Leu (correlation coefficient = ?0.93). "All-??" proteins tend to have a higher content of Tyr, Trp, Gln and Ser, whereas "??/??" proteins tend to have a higher content of Val, Ile and Leu.

Conclusions

The ??-helix propensities are similar for all folds and for exposed and buried residues. However, ??-sheet propensities calculated for exposed residues differ from those for buried residues, indicating that the exposed-residue fraction is one of the major factors governing amino acid composition in ??-strands. Furthermore, the correlations we detected suggest that amino acid composition is related to folding properties such as the twist of a ??-strand or association between two ?? sheets.     

A novel application of capnography during controlled human exposure to air pollution

Background

A detailed contrast bolus propagation model is essential for optimizing bolus-chasing Computed Tomography Angiography (CTA). Bolus characteristics were studied using bolus-timing datasets from Magnetic Resonance Angiography (MRA) for adaptive controller design and validation.

Methods

MRA bolus-timing datasets of the aorta in thirty patients were analyzed by a program developed with MATLAB. Bolus characteristics, such as peak position, dispersion and bolus velocity, were studied. The bolus profile was fit to a convolution function, which would serve as a mathematical model of bolus propagation in future controller design.

Results

The maximum speed of the bolus in the aorta ranged from 5–13 cm/s and the dwell time ranged from 7–13 seconds. Bolus characteristics were well described by the proposed propagation model, which included the exact functional relationships between the parameters and aortic location.

Conclusion

The convolution function describes bolus dynamics reasonably well and could be used to implement the adaptive controller design.