Postprandial interstitial insulin concentrations in type 2 diabetes relatives.

Background: An endothelial barrier for the insulin transport from the circulation to the target tissues of insulin has previously been suggested to contribute to insulin resistance. The interstitial insulin concentration (I-insulin) and insulin kinetics following a mixed meal have, however, previously not been characterized in human adipose tissue.

Subjects And Methods: Eight nondiabetic first-degree relatives (FDR) of type 2 diabetes patients were recruited.

Chronic itch and pain--similarities and differences.

Both, pruritus and pain are aversive, but clearly distinct sensations originating in the peripheral and central nervous system. During the last years, many interactions between itch and pain in acute transmission and sensitization processes have been identified. It is common experience that the itch sensation can be reduced by the painful sensations caused by scratching.

Frontiers in pruritus research: scratching the brain for more effective itch therapy.

This Review highlights selected frontiers in pruritus research and focuses on recently attained insights into the neurophysiological, neuroimmunological, and neuroendocrine mechanisms underlying skin-derived itch (pruritogenic pruritus), which may affect future antipruritic strategies. Special attention is paid to newly identified itch-specific neuronal pathways in the spinothalamic tract that are distinct from pain pathways and to CNS regions that process peripheral pruritogenic stimuli. In addition, the relation between itch and pain is discussed, with emphasis on how the intimate contacts between these closely related yet distinct sensory phenomena may be exploited therapeutically.

Pathophysiology and treatment of pain in joint disease.

Deep somatic pain originating in joints and tendons is a major therapeutic challenge. Spontaneous pain and mechanical hypersensitivity can develop as a consequence of sensitization of primary afferents directly involved in the inflammatory process, but also following sensitization of neuronal processing in the spinal cord (central sensitization) or higher centres. Inflammatory pain is linked to sensitization of sensory proteins at the nociceptive endings whereas pain originating from nerve damage (neuropathic pain) has been linked to changes in axonal ion channels producing ectopic discharge in nociceptors as a source of pain.

[Interactions between itch and pain].

The discovery of specific pathways for the processing of itch has greatly enhanced our understanding of the physiology of pruritus. However, the complex interactions between itch and pain are only partly understood. This review focuses on the neurophysiological basis of itch under experimental and clinical conditions.

[Clinical classification of chronic pruritus. Interdisciplinary consensus proposal for a diagnostic algorithm].

Chronic pruritus is a frequent symptom in dermatology caused by a variety of dermatologic, neurologic and other systemic diseases. For adequate, economically-appropriate medical care of patients with chronic pruritus, a clinical classification of pruritus which also serves as a diagnostic algorithm is necessary. Currently suggested classifications are etiologic and not helpful in daily clinical routine.

[Respiratory failure due to delta-9-tetrahydrocannabinol in a tetraplegic patient].

We report on a patient with an incomplete tetraplegia below C2 who suffered from a post-traumatic abdominal spasticity, spasticity of the legs, and bladder contractions of high intensity. Breathing was possible during the day using accessory respiratory musculature. All standard therapeutic regimes against spasticity failed.

Duration of effects of aspirin on platelet function in healthy volunteers: an analysis using the PFA-100.

Study Objective: The aim of the study was to determine the duration and effects of aspirin on platelet function.

Study Design: Prospective investigation.

Setting: Blood samples from volunteers.

Angiotensin converting enzyme has an inhibitory role in CGRP metabolism in human skin.

The neutral endopeptidase (NEP) is important for calcitonin gene related peptide (CGRP) degradation, while the role of angiotensin converting enzyme (ACE) remains unclear. By using dermal microdialysis we explored the effect of phosphoramidon (NEP blocker), captopril (ACE blocker) and a mixture of both drugs on the intensity of electrically-induced CGRP-mediated neurogenic flare. The results reveal that phosphoramidon elevated flare intensity, but that this was not further increased by adding captopril.

Neurogenic components of trypsin- and thrombin-induced inflammation in rat skin, in vivo.

Activation of protease-activated receptors (PAR) can induce vasodilation (VD) and increase of vascular permeability either directly by stimulating endothelial cells or indirectly via activation of nociceptors and subsequent release of neuropeptides (neurogenic inflammation). We aimed to estimate the relative contribution of the two pathways for stimulation with endogenous activators of PAR-2 (trypsin) and of PAR-1, 3 and 4 (thrombin) using in vivo dermal microdialysis in rats. Protein extravasation (PE) was assessed by increase of protein concentration in the dialysate, and VD was quantified by laser Doppler scanning.

Itch and pain.

The discovery of a specialized neuronal pathway for itch has markedly improved our understanding of itch processing under physiological conditions. However, the complex interactions of pain and itch are only partly understood. This review focuses on the neurophysiological mechanisms involved in clinical and experimental itch conditions.

Activation of naloxone-sensitive and -insensitive inhibitory systems in a human pain model.

Unlabelled: We investigated naloxone effects in a model of electrically induced pain and hyperalgesia. In a double-blind, placebo-controlled, cross-over study, 15 volunteers underwent four 150-minute sessions of high-current-density electrical stimulation of their forearms. After 60 minutes, naloxone or placebo was given intravenously (increasing plasma concentrations of 0.

Different profiles of buprenorphine-induced analgesia and antihyperalgesia in a human pain model.

Different mechanisms were proposed for opioid-induced analgesia and antihyperalgesia, which might result in different pharmacodynamics. To address this issue, the time course of analgesic and antihyperalgesic effects of intravenous (i.v.

Integrin-dependent amplification of the G2 arrest induced by ionizing radiation.

The progressive loss of laminin 5 and the alpha6beta4 integrin is a characteristic of the transition of prostatic intraepithelial neoplasia (PIN) to invasive human prostate cancer. Our objective was to determine if the loss of the interaction with laminin 5 would influence the ability of human epithelial cells to respond to DNA damage. Three cellular damage responses to ionizing radiation (IR) were analyzed including G2 progression, cdc2 phosphorylation, and cell survival.

[Mechanisms in the development of pain. Key issue in the periphery].

The interaction between neurons, tissue cells and inflammatory cells is of major importance for the development of pain in the periphery. In this interaction a variety of inhibitory and activating circuits has been identified in recent years. In addition to the receptors for classical inflammatory mediators on the sensory terminals like bradykinin, axonal ion channels have been identified as major modulators of pain and sensitization apart from their traditional role in conduction of action potentials.

Cellular immune suppressor activity resides in lymphocyte cell clusters adjacent to granulomata in human coccidioidomycosis.

The in situ immunologic response in human coccidioidomycosis remains undefined. To explore this further, pulmonary necrotizing coccidioidal granulomata were examined using immunohistochemical staining for lymphocyte subsets and for the cytokines interleukin-10 (IL-10) and gamma interferon (IFN-gamma). Discrete perigranulomatous lymphocytic clusters were seen in eight of nine tissues examined.

Inhibition of neutral endopeptidase (NEP) facilitates neurogenic inflammation.

Neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) are involved in neuropeptide degradation and may modulate neurogenic inflammation. We therefore explored the effect of specific blockers of NEP and ACE on the intensity of neurogenic inflammation. We investigated eight subjects on three occasions.

Distribution of cannabinoid receptor 1 (CB1) and 2 (CB2) on sensory nerve fibers and adnexal structures in human skin.

Background: Cannabinoid receptors mediate the psychopharmacological action of marijuana and have been localized in the central and peripheral nervous system as well as on cells of the immune system.

Objective: Up to now, two cannabinoid receptors (CB1 and CB2) have been cloned and recent studies on animal tissue gave evidence for the presence of cannabinoid receptors in the skin.

Methods: In the present immunohistochemical investigation we determined the precise localization of CB1 and CB2 in sections of human skin and in one case of mastocytosis.

Identification of a stem cell candidate in the normal human prostate gland.

Stem cells of the human prostate gland have not yet been identified utilizing a structural biomarker. We have discovered a new prostatic epithelial cell phenotype-expressing cytokeratin 6a (Ck6a+ cells). The Ck6a+ cells are present within a specialized niche in the basal cell compartment in fetal, juvenile and adult prostate tissue, and within the stem cell-enriched urogenital sinus.

How best to fight that nasty itch - from new insights into the neuroimmunological, neuroendocrine, and neurophysiological bases of pruritus to novel therapeutic approaches.

While the enormous clinical and psychosocial importance of pruritus in many areas of medicine and the detrimental effects of chronic 'itch' on the quality of life of an affected individual are widely appreciated, the complexity of this sensation is still often grossly underestimated. The current Controversies feature highlights this complexity by portraying pruritus as a truly interdisciplinary problem at the crossroads of neurophysiology, neuroimmunology, neuropharmacology, protease research, internal medicine, and dermatology, which is combated most successfully if one keeps the multilayered nature of 'itch' in mind and adopts a holistic treatment approach - beyond the customary, frequently frustrane monotherapy with histamine receptor antagonists. In view of the often unsatisfactory, unidimensional, and altogether rather crude standard instruments for pruritus management that we still tend to use in clinical practice today, an interdisciplinary team of pruritus experts here critically examines recent progress in pruritus research that future itch management must take into consideration.

Transcutaneous penetration of toluene in rat skin a microdialysis study.

Percutaneous absorption of lipophilic substances has major implications for therapeutical use or toxicological effects. We, therefore, using dermal microdialysis, measured local toluene concentrations and assessed the effects of duration of exposure, skin barrier disruption and the use of skin-care products. Three microdialysis membranes (3000 kDa) were inserted intradermally at a length of 2 cm in the abdominal skin of 82 anaesthetized male Wistar rats.

Electrically evoked itch in humans.

We compared itch sensations and axon reflex flare induced by transcutaneous electrical (0.08-8 ms, 2-200 Hz) and chemical (histamine iontophoresis; 100 microC) stimulation. Stimuli were applied to non-lesional volar wrist skin in 20 healthy human subjects and 10 patients with atopic dermatitis.

The effect of intravenous infusion of adenosine on electrically evoked hyperalgesia in a healthy volunteer model of central sensitization.

Human pain models invoking central sensitization, one of the key mechanisms of chronic pain, may be useful for characterizing new analgesics. A new model of electrical hyperalgesia can detect the efficacy of several analgesic mechanisms. Because IV adenosine can alleviate neuropathic pain, we investigated its effect on experimental sensitization.