Annals of the New York Academy of Sciences
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Ann. N. Y. Acad. Sci. · Jun 2002
Review Comparative StudyNeuropeptides in experimental and degenerative arthritis.
Classical symptoms of both inflammatory and degenerative arthritides may contribute to neurogenic responses like wheal, flare, edema, and pain. Rheumatoid arthritis (RA) is an autoimmune disease with an immunogenetic background. Neurogenic inflammation has been considered to play an essential role in RA, in part because of the symmetrical involvement (cross-spinal reflexes) and the predominant involvement of the most heavily innervated small joints of the hands and the feet (highly represented in the hominiculus). ⋯ Neuropeptides serve as messengers, which modulate and mediate the actions in these cascades. Accordingly, many neuropeptides have been used successfully as experimental treatments, most recently VIP, which effectively controlled collagen-induced arthritis in mice. Therefore, it can safely be concluded that better treatment/control of disease activity and pain can be achieved by blocking the cascade leading to initiation and/or amplification of inflammatory process combined with effects on central nociceptive and neuroendocrine responses.
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A chronic minor imbalance between energy intake and energy expenditure may lead to obesity. Both lean and obese subjects eventually reach energy balance and their body weight regulation implies that the adipose tissue mass is "sensed", leading to appropriate responses of energy intake and energy expenditure. The cloning of the ob gene and the identification of its encoded protein, leptin, have provided a system signaling the amount of adipose energy stores to the brain. ⋯ Conversely, it is unlikely that leptin has evolved to prevent obesity when plenty of palatable foods are available because the elevated plasma leptin levels resulting from the increased adipose tissue mass do not prevent the development of obesity. In conclusion, in humans, the leptin signaling system appears to be mainly involved in maintenance of adequate energy stores for survival during periods of energy deficit. Its role in the etiology of human obesity is only demonstrated in the very rare situations of absence of the leptin signal (mutations of the leptin gene or of the leptin receptor gene), which produces an internal perception of starvation and results in a chronic stimulation of excessive food intake.
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Inflammation in the joint causes peripheral sensitization (increase of sensitivity of nociceptive primary afferent neurons) and central sensitization (hyperexcitability of nociceptive neurons in the central nervous system). The processes of sensitization are thought to be the basis of arthritic pain that appears as spontaneous pain (joints at rest) and hyperalgesia (augmented pain response on noxious stimulation and pain on normally nonpainful stimulation). Sensitization also facilitates efferent neuronal processes through which the nervous system influences the inflammatory process. ⋯ Central sensitization also is facilitated by mediators that have complex actions (e.g., prostaglandin E(2)). Spinal PGE(2) binds to receptors at presynaptic endings of primary afferent neurons (thus influencing synaptic release) and to receptors on postsynaptic spinal cord neurons. The administration of PGE(2) to the spinal cord surface produces changes of responsiveness of spinal neurons similar to peripheral inflammation, and spinal indomethacin to the spinal cord attenuates development of hyperexcitability significantly.
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Ann. N. Y. Acad. Sci. · Apr 2002
ReviewBeta cell rest and recovery--does it bring patients with latent autoimmune diabetes in adults to euglycemia?
Diabetes mellitus in humans is a heterogeneous disorder classified clinically into two main types. The diagnosis of type 1 versus type 2 diabetes is made phenotypically using criteria such as age at onset, abruptness of hyperglycemic symptoms, presence of ketosis, degree of obesity and the perceived need for insulin replacement. The pathogeneses of type 1 and type 2 diabetes are believed to be different. ⋯ The disease of these autoantibody-positive type 2 diabetics is often termed latent autoimmune diabetes in adults (LADA), slowly progressive type 1 diabetes, latent type 1 diabetes, and type 1.5 diabetes. This group of patients comprises approximately 10-15% of Caucasian type 2 diabetes patients. Type 1.5 diabetes patients tend to present with islet cell autoantibodies, islet-reactive T cells, higher HbA(1c) levels, lower C peptide, and a propensity toward insulin dependency compared to autoantibody-negative classic type 2 diabetes subjects.
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Retrograde menstruation has been suggested to be the cause for the presence of endometrial cells in the peritoneal cavity. However, little is known about the events that lead to the adhesion and growth of these cells that ultimately result in endometriosis, considering the fact that the disease occurs only in certain women despite the common occurrence of retrograde menstruation in most women. We postulate that, in normal women, the endometrial cells and tissue that arrive in the peritoneal cavity during menstruation are effectively removed by macrophages that are chemoattracted and become resident tissue macrophages in the peritoneal cavity. ⋯ We provide evidence for the presence of oxidative milieu in the peritoneal cavity of women with endometriosis, the nonscavenging properties of macrophages that are nonadherent, and the synergistic interaction between macrophages, oxidative stress, and the endometrial cells. For example, the peritoneal fluid lipoproteins of subjects with endometriosis have increased the propensity to undergo oxidation as compared with plasma lipoproteins, and the subjects also have increased titer of autoantibodies to oxidatively modified proteins. If the oxidative proinflammatory nature of the peritoneal fluid is an important mediator of endometriosis growth, anti-inflammatory agents and antioxidants might afford protection against endometriosis.