ABSTRACT
CAREPATH project is focusing on providing an integrated solution for sustainable care for multimorbid elderly patients with dementia or mild cognitive impairment. The project has a digitally enhanced integrated patient-centered care approach clinical decision and associated intelligent tools with the aim to increase patients' independence, quality of life and intrinsic capacity. In this paper, the conceptual aspects of the CAREPATH project, in terms of technical and clinical requirements and considerations, are presented.
Subject(s)
Cognitive Dysfunction , Delivery of Health Care, Integrated , Dementia , Aged , Dementia/therapy , Humans , Multimorbidity , Quality of LifeABSTRACT
Marmosets are used as preclinical model in reproductive research. In contrast to other primates, they display short gestation times rendering this species valid for exploration of effects on fertility. However, their peculiar endocrine regulation differs from a those of macaques and humans. We subjected male marmosets to previously clinically tested hormonal regimens that are known to effectively suppress spermatogenesis. Beside a control group, seven groups (each n=6) were investigated for different periods of up to 42 months: regimen I, (four groups) received testosterone undecanoate (TU) and norethisterone enanthate (NETE); regimen II, (two groups) received TU and NETE followed by NETE only; and regimen III, (one group) received NETE only. Testicular volume, cell ploidy and histology, endocrine changes and fertility were monitored weekly. TU and NETE and initial TU and NETE treatment followed by NETE failed to suppress spermatogenesis and fertility. Testicular volumes dropped, although spermatogenesis was only mildly affected; however, testicular cellular composition remained stable. Serum testosterone dropped when NETE was given alone but the animals remained fertile. Compared with controls, no significant changes were observed in sperm motility and fertility. Administration of TU and NETE affected testicular function only mildly, indicating that the regulatory role of chorionic gonadotrophin and testosterone on spermatogenesis is obviously limited and testicular function is maintained, although the endocrine axis is affected by the treatment. In conclusion, marmosets showed a different response to regimens of male contraception from macaques or men and have to be considered as a problematic model for preclinical trials of male hormonal contraception.
Subject(s)
Antispermatogenic Agents/administration & dosage , Callithrix/blood , Fertility/drug effects , Norethindrone/analogs & derivatives , Testosterone/analogs & derivatives , Animals , Body Weight/drug effects , Chorionic Gonadotropin/metabolism , Epididymis/drug effects , Male , Models, Animal , Norethindrone/administration & dosage , Organ Size , Pituitary Gland/metabolism , Ploidies , Sperm Motility , Testis/drug effects , Testis/metabolism , Testosterone/administration & dosage , Testosterone/bloodABSTRACT
PURPOSE OF REVIEW: Recent studies have advanced our understanding that allergic inflammation triggers neuronal dysfunction, thereby modulating inflammation-related changes in affected tissues including the skin. Vice versa, evidence has emerged that inflammatory responses are controlled by neurons. Moreover, structural cells and invading immune cells express neuronal receptors and release mediators which directly communicate with nerve endings in the skin. RECENT FINDINGS: During the allergic response, skin cells do not only represent a significant source of neuromediators but also represent targets for neuropeptides or neurotrophins as well as neurotransmitters in the inflamed tissue. During the last decade, it has become obvious that a large variety of molecules influence the adaptive as well as the innate immune response. Beside neuropeptide receptors, proteinase-activated receptors, novel histamine receptors, different cytokine or chemokine receptors play a role in the pathophysiology of atopic and allergic diseases. SUMMARY: Peripheral sensory and autonomic nerves are critically involved in many pathways of the innate and adoptive immune system during allergic and atopic skin diseases. Further dissection of receptor-mediated and intracellular signal pathways will help to develop more effective therapeutic approaches for allergic and inflammatory skin diseases.
Subject(s)
Hypersensitivity/immunology , Neurogenic Inflammation/immunology , Neuroimmunomodulation/immunology , Neuropeptides/immunology , Skin Diseases/immunology , Allergens/immunology , Allergens/metabolism , Animals , Cytokines/immunology , Cytokines/metabolism , Humans , Hypersensitivity/metabolism , Ion Channels/metabolism , Neurogenic Inflammation/metabolism , Neuropeptides/metabolism , Peripheral Nervous System/immunology , Peripheral Nervous System/metabolism , Skin/innervation , Skin Diseases/metabolism , Skin Diseases/physiopathologyABSTRACT
Atopic dermatitis (AD) lesions are characterized by differences in the activation state of endothelial cells and vascular smooth muscle cells and the release of inflammatory mediators by and toward the vasculature. The vascular system, including endothelial cells and smooth muscle cells, is ultimately involved in clinical symptoms of AD, such as erythema, edema, leukocyte recruitment, and white dermographism. Various mediators and bidirectional neurovascular interactions regulate the inflammatory response during AD. T cell-endothelial cell interactions are a crucial component to establish acute AD. Various immune cells, including monocytes and mast cells, communicate with the endothelium by releasing inflammatory mediators, thereby stimulating inflammatory mediator release from activated endothelial cells. The process of adhesion, tethering, and transmigration of infiltrating cells is a highly regulated and an active communication process between endothelial cells and leukocytes. Endothelial cells play a pivotal role in the pathophysiology of AD and represent future targets for the treatment of AD.
