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Food from the sea can make a larger contribution to healthy and sustainable diets, and to addressing hunger and malnutrition, through improvements in production, distribution and equitable access to wild harvest and mariculture resources and products. The supply and consumption of seafood is influenced by a range of 'drivers' including ecosystem change and ocean regulation, the influence of corporations and evolving consumer demand, as well as the growing focus on the importance of seafood for meeting nutritional needs. These drivers need to be examined in a holistic way to develop an informed understanding of the needs, potential impacts and solutions that align seafood production and consumption with relevant 2030 Sustainable Development Goals (SDGs). This paper uses an evidence-based narrative approach to examine how the anticipated global trends for seafood might be experienced by people in different social, geographical and economic situations over the next ten years. Key drivers influencing seafood within the global food system are identified and used to construct a future scenario based on our current trajectory (Business-as-usual 2030). Descriptive pathways and actions are then presented for a more sustainable future scenario that strives towards achieving the SDGs as far as technically possible (More sustainable 2030). Prioritising actions that not only sustainably produce more seafood, but consider aspects of access and utilisation, particularly for people affected by food insecurity and malnutrition, is an essential part of designing sustainable and secure future seafood systems. Supplementary Information: The online version contains supplementary material available at 10.1007/s11160-021-09663-x.

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BACKGROUND: Vinorelbine is a vinca alkaloid obtained by hemisynthesis, which makes the molecule more lipophilic than the other vincas. An injectable formulation is already marketed for the treatment of non small cell lung cancer (NSCLC) and advanced breast cancer (ABC). A new oral form has been developed and its file registration is being submitted. As part of its development, a clinical study was conducted to determine the absolute bioavailability and pharmacokinetics of oral vinorelbine administered as softgel capsules, and to evaluate its safety profile compared with intravenous administration. PATIENTS AND METHODS: Thirty-two patients with solid tumours were included in the study. Patients fasted and were randomised to receive vinorelbine on day 1, either as a 20 minute intravenous (i.v.) infusion of 25 mg/m2 or as softgel capsules at a dose of 80 mg/m2. Patients were treated with the alternate route after a one week wash-out period. Blood and urine samples for pharmacokinetic analysis were collected during each vinorelbine administration. Safety was assessed after each administration using the CALGB/expanded CTC classification. RESULTS: Twenty-four patients were eligible for pharmacokinetic evaluation. Oral vinorelbine was rapidly absorbed at 80 mg/m2 (Tmax 1.4 +/- 0.7 h) and showed a bioavailability of 43 +/- 14, and close to 40% based on AUC(last) and AUC(inf), respectively. A bioequivalence analysis was conducted on dosage-normalised blood exposures. Equivalence was demonstrated between 80 mg/m2 oral and 30 mg/m2 i.v., and between 60 mg/m2 oral and 25 mg/m2 i.v. The inter-individual variability was equivalent for both routes (CV: 38% and 39% for oral and i.v., respectively). A correlation was found in both methods between AUClast and % nadir variation in white blood cells (WBC) and polymorphonuclears (PMN). More cases of neutropenia (all grades pooled), leucopenia (grades 3-4 only) and nausea (grades 2-3) were induced by 80 mg/m2 oral vinorelbine than by 25 mg/m2 i.v. The greatest intensity of these effects, following oral administration, probably reflects the higher, observed drug exposure. CONCLUSION: At therapeutic dosage levels, pharmacokinetic behaviour and safety profiles were similar for both routes. The absolute bioavailability of the oral vinorelbine (new, soft gelatine capsule) was close to 40%. Inter-individual variability in drug exposure was equivalent in both routes. The pharmacokinetic/pharmacodynamic (PK/PD) relationship in haematological toxicity was independent of the routes of administration. Reliable, corresponding doses between oral and i.v. vinorelbine were established, which will result in bioequivalent AUC.

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Several chronic inflammatory changes undergone during chronic haemodialysis are associated with increased pro-inflammatory cytokine production. Although generation of anaphylatoxins has been incriminated in the untoward effects of haemodialysis, it is still debated whether anaphylatoxins stimulate monocyte secretion of TNF-alpha and IL-1. We demonstrate that peripheral mononuclear cells isolated from healthy controls and cultured with complement-activated autologous serum or recombinant C5a induced high levels of IL-1, IL-1ra, IL-8 and MCP-1, low levels of TNFalpha and sTNFRII but no IL-10 and MIP-1alpha. Cytokine production by leukocytes was investigated by FACS analysis in six patients dialysed consecutively with three equivalent low permeability membranes known to activate the complement to different degrees: polysulfone (F6HPS), cellulose acetate (CA) and cuprophane (CP). Percentage of leukocytes expressing IL-1, IL-1ra, TNF-alpha and IL-8 is increased in patients dialysed with CP. Moreover, we show for the first time that haemodialysis is associated with the production of cytokines by circulating neutrophils. Predialysis plasma levels of MCP-1 and TNFRII did not increase during the dialysis session at the time when anaphylatoxin generation was highest. Dialysis with membranes that activate the complement to a high extent induce activation of leukocytes which may explain chronic complications associated with dialysing with CP.

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Complement activation, neutrophil stimulation, increased cellular adhesiveness, transient leukocyte margination and pulmonary leukostasis take place during hemodialysis with cellulosic dialysis membranes. Several investigators have hypothesized that complement activation is primarily responsible for the acute neutropenia occurring during the early phase of bio-incompatible hemodialysis. We have investigated the relationship between complement activation, levels of expression of CD11b and CD61 integrins on neutrophils and platelets, neutrophil counts and blood gas measurements in patients dialyzed with three types of membranes, known to activate the complement system to a different extent. Polysulfone, cellulose acetate and cuprophane membranes were used subsequently in six patients in a prospective cross-over trial design to reduce inter-individual variability. Increased levels of CD61 and CD11b, as well as neutropenia, were detected regardless of the type of membrane used. We observed a high inter-individual variation with regard to complement activation suggesting varying susceptibility to dialysis membranes. We also report that the kinetics of anaphylatoxin generation were dissociated from those of the upregulation of adhesion molecules, early neutrophil margination and decrease in PaO2 during the first 30 min of hemodialysis. Similar results were obtained with all three types of dialysis membranes. The data strengthen the hypothesis that factors other than complement are involved in the induction of dialysis-related neutropenia and hypoxemia.

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BACKGROUND: beta-2 microglobulin is predominant in amyloid deposits in patients undergoing long term hemodialysis. Amyloid accumulation has been ascribed to dialysis membranes, endotoxin contamination of the dialysate, uremia and chronic systemic inflammation associated with enhanced monocytic cytokine production in hemodialyzed patients. Interleukin-1 has been proposed to play a critical role in the induction of beta-2 microglobulin synthesis and release. METHODS: We examined if monocytes contribute to beta-2 microglobulin production upon stimulation with inflammatory mediators that are generated during hemodialysis and investigated the production of beta-2 microglobulin by cells from patients, with and without clinical signs of amyloidosis, at the time when patients' monocytes contained maximal intracellular accumulation of IL-1. RESULTS: We demonstrated that only monocytes are able to release increased levels of beta-2 microglobulin upon stimulation by IL-1, TNF alpha, C5a and LPS. Increased levels of beta-2 microglobulin were associated with increased levels of beta-2 microglobulin mRNA. Before dialysis session, 20-60% of circulating CD14+ monocytes from patients contained IL-1. At the time when maximal IL-1 production was detected, we showed by RT-PCR increased transcription of IL-1 gene in patients' monocytes. We observed that monocytes from patients with amyloidosis contained higher amounts of IL-1 as compared to monocytes from patients without clinical signs of amyloidosis, but could not secrete increased amounts of beta-2 microglobulin upon LPS-stimulation. CONCLUSIONS: Our data indicated that chronic inflammation, as demonstrated by increased intracellular IL-1 expression, is not associated with increased production of beta-2 microglobulin by monocytes from patients on hemodialysis.

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We have used two-color flow cytometry to study in vivo monocytic cytokine production at the single-cell level in HIV-infected patients. We demonstrated the presence of intracellular IL-1 alpha, IL-1 beta, IL-1ra, and TNF alpha in circulating CD14+ monocytes from HIV-infected patients. The specificity of intracellular staining with anti-cytokine antibodies was demonstrated by the suppression of the fluorescent signal when staining was performed in the presence of recombinant cytokines. We did not detect any specific intracellular staining when anti-IL-4 antibodies were used since monocytes do not produce IL-4. In vivo intracellular cytokine production of IL-1 alpha, IL-1 beta, IL-1ra, and TNF alpha was higher in monocytes from HIV-infected individuals compared to monocytes from healthy controls; however, only the data concerning IL-1 alpha reached statistical significance. Monocytic cytokines are involved in the regulation of HIV gene expression and may participate in the modulation of the Th1/Th2 balance. The ability to follow the production of a wide range of cytokines by circulating monocytes of HIV-infected patients should allow one to better analyze the role of monocytic cytokines in the pathogenesis of HIV disease.

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Cellular interactions are controlled by complex mechanisms which come into play at the receptors on the cell surface (adhesion molecules: selectins, integrins, superfamily of immunoglobulins), the soluble cell mediators (cytokines) and the components of the tissue matrix (fibronectin, collagen, etc.). Disturbance of one of these systems may induce a pathological condition. The physiological state of the individual therefore depends on the balance of all these components. In the development of inflammation, adhesion molecules play an essential role in the localisation of the inflammatory response. At this level, the vascular endothelium, a governing barrier for the exchanges between blood and the tissues, plays an active part in regulation of the transcapillary permeability, control of proliferation of haematopoietic cells and the phases of the inflammatory response. After they have marginated, the active cells migrate by diapedesis towards the site of inflammation by creation of chemotactic signals as the adhesion between the cells is insufficient to induce their migration. The adherence phenomena depend on a process that is strictly controlled by the cytokines and enable intervention of cell-cell reactions and cell-protein recognition of the extra-cellular matrix. Cytokines play a key role in control of the expression and/or avidity of membrane receptors for ligand(s). An appropriate and rapid response of the circulating cells depends on coordination of the train of events that regulate the functional expression of the adhesion molecules. Use of specific antibodies that prevent cell adherence opens very important therapeutic possibilities because a single blockage of cell adhesion can have an immediate direct impact on development of the inflammatory response.

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