NERVE AS MODEL TEMPERATURE END ORGAN

We studied the ability of typical unmyelinated cortical axons to conduct action potentials at fever‐like temperatures because fever often gives CNS symptoms. We investigated such axons in cerebellar and hippocampal slices from 10 to 25 days old rats at temperatures between 30 and 43°C. By recording with two electrodes along axonal pathways, we confirmed that the axons were able to initiate action potentials, but at temperatures >39°C, the propagation of the action potentials to a more distal recording site was reduced. This temperature‐sensitive conduction may be specific for the very thin unmyelinated axons because similar recordings from myelinated CNS axons did not show conduction failures. We found that the conduction fidelity improved with 1 mmol/L TEA in the bath, probably due to block of voltage‐sensitive potassium channels responsible for the fast repolarization of action potentials. Furthermore, by recording electrically activated antidromic action potentials from the soma of cerebellar granule cells, we showed that the axons failed less if they were triggered 10–30 msec after another action potential. This was because individual action potentials were followed by a depolarizing after‐potential, of constant amplitude and shape, which facilitated conduction of the following action potentials. The temperature‐sensitive conduction failures above, but not below, normal body temperature, and the failure‐reducing effect of the spike's depolarizing after‐potential, are two intrinsic mechanisms in normal gray matter axons that may help us understand how the hyperthermic brain functions.

Chapter 13 - Nicotinic acetylcholine receptors in the autonomic nervous system

During intracellular recording from cat spinal motoneurons, the lumbo-sacral cord was subjected to rapid local temperature changes. Cooling to 30° C causes a decrease in the resting membrane potential (RMP), a transient increase in spike overshoot, and increases in the input resistance and the durations of both the action potential and the hyperpolarizing after-potential (HAP). Warming causes these membrane parameters to change in the opposite direction and can result in a failure of antidromic activation. The RMP changes are dependent upon the RMP at normal temperature, being negligible in cells having an initial RMP greater than 70 mV. The Q10-values of the three peaks of the differentiated spike are relatively high and nearly identical to the Q10-values of the corresponding rate constants for sodium activation and inactivation and potassium activation measured by Frankenhaeuser and Moore in toad nerve fibers, i.e. 1.71, 2.35 and 3.12, respectively. Delayed sodium inactivation and potassium activation explain the increase in spike overshoot observed during cooling, and the high Q10 of potassium activation is nearly identical to the Q10 of the time to peak of the HAP (3.12 vs. 2.97). The decrease in RMP during cooling is attributed to a decrease in the PK∶PNa ratio rather than to a blockage of an electrogenic sodium pump; the differences in RMP temperature sensitivities between cells with high and low initial RMP's might be due to a higher resting PK (anomalous rectification) at higher RMP. We conclude that the electrogenic pump does not normally contribute significantly to the RMP of cat motoneurons.

2.20 - Evolution of Taste

Temperature gradient across the skin’s layers has no influence on local skin vasomotor responses

Our sense of touch emerges from an array of mechanosensory structures residing within the fabric of our skin. These tactile end organ structures convert innocuous forces acting on the skin into electrical signals that propagate to the CNS via the axons of low-threshold mechanoreceptors (LTMRs). Our rich capacity for tactile discrimination arises from the dissimilar intrinsic properties of the LTMR subtypes that innervate different regions of the skin and the structurally distinct end organ complexes with which they associate. These end organ structures comprise a range of non-neuronal cell types, which may themselves actively contribute to thetransformation of tactile forces into neural impulses within the LTMR afferents. Although the mechanism and the site of transduction across end organs remain unclear, PIEZO2 has emerged as the principal mechanosensitive channel involved in light touch of the skin. Here we review the physiological properties of LTMR subtypes and discuss how features of their cutaneous end organ complexes shape subtype-specific tuning.

BackgroundAcute or chronic tissue damage induces an inflammatory response accompanied by pain and alterations in local tissue temperature. Recent studies revealed that the transient receptor potential A1 (TRPA1) channel is activated by a wide variety of substances that are released following tissue damage to evoke nociception and neurogenic inflammation. Although the effects of a noxious range of cold temperatures on TRPA1 have been rigorously studied, it is not known how agonist-induced activation of TRPA1 is regulated by temperature over an innocuous range centred on the normal skin surface temperature. This study investigated the effect of temperature on agonist-induced currents in human embryonic kidney (HEK) 293 cells transfected with rat or human TRPA1 and in rat sensory neurons.ResultsAgonist-induced TRPA1 currents in HEK293 cells were strongly suppressed by warm temperatures, and almost abolished at 39°C. Such inhibition occurred when TRPA1 was activated by either electrophilic or non-electrophilic agonists. Warming not only decreased the apparent affinity of TRPA1 for mustard oil (MO), but also greatly enhanced the desensitization and tachyphylaxis of TRPA1. Warming also attenuated MO-induced ionic currents in sensory neurons. These results suggest that the extent of agonist-induced activity of TRPA1 may depend on surrounding tissue temperature, and local hyperthermia during acute inflammation could be an endogenous negative regulatory mechanism to attenuate persistent pain at the site of injury.ConclusionThese results indicate that warmth suppresses and desensitizes damage-sensing ion channel TRPA1. Such warmth-induced suppression of TRPA1 may also explain, at least in part, the mechanistic basis of heat therapy that has been widely used as a supplemental anti-nociceptive approach.

SUMMARYA heat-exchange chamber made of perspex was inserted beneath the skin of a Merino sheep. By passing water at predetermined temperatures through the chamber, the normal subdermal temperature of 37°C was raised approximately 4°C for 4 days, then lowered approximately 5°C for 4 days.In response to heating, the animal's temperature regulating mechanism was able to maintain a fairly constant subdermal temperature. However, it was unable to maintain as constant a subdermal temperature in response to cooling. There was, during the cooling period, an obvious nervous response to environmental disturbances manifested by sudden transient decreases in subdermal temperature over the chamber.During the cooling period there was a decrease of 12% in mean length growth rate of wool over the chamber but mean fibre diameter was unchanged. Heating produced a small decrease in mean fibre diameter, but no change in mean length growth rate. Heating appeared to produce a slight reduction in pigmentation of some fibres but neither heating nor cooling produced demonstrable changes in crimping.

Background: Anatomical variations in visceral arteries are not so uncommon (up to 20% of cases in general population), with splenic and hepatic artery anomalies being the most frequently reported. Aberrant arteries may be affected with aneurysmal lesions that are rare but potentially fatal conditions. In their treatment, a comprehensive understanding and knowledge of the underlining anatomical variation are pivotal to prevent potential ischemic complications for the end organ. Methods: A comprehensive literature search on the PubMed, Cochrane and Scopus databases was done using the terms: "anomalous visceral artery aneurysm", "Aberrant visceral arteries", and "anomalous origin visceral vessels". Eligible studies published from inception to 30 June 2024 were identified. Only those that had included the adopted treatment strategies (open, endovascular or hybrid repair) and the related outcomes (mortality, bleeding, end-organ ischemia, lesions of the surrounding organ, need for reintervention) were analyzed to evaluate the safety and efficacy of each approach. A narrative analysis of the indications informing the selection of each interventional treatment, based on individual procedural risks, was also presented. Results: A total of 30 publications describing 36 patients (mean age 48.9 ± 12.8 years, range 22-73 years) with aneurysms involving aberrant visceral arteries were included. Most patients were female (25/36, 69.4%). True aneurysms predominated (with a mean size of 30.5 ± 11.5 mm, range 6-60 mm), being reported in 33/36 (91.7%) patients. Most lesions involved a splenic artery arising from the superior mesenteric artery (27/36, 75.0%). Overall, 26/36 (72.2%) patients were symptomatic upon presentation, most commonly with abdominal or epigastric pain, often associated with nausea or vomiting, back pain or shortness of breath. All patients underwent preoperative Computed angiotomography or subtraction angiography to define the operative strategy. Most cases were managed electively (31/36, 86.1%), but 11.1% (4/36) of cases required urgent intervention (in one case the urgency status was not specified). Overall, 19/36 (52.8%) patients underwent purely endovascular repair, 15/36 (41.7%) were treated with open surgery, and 2/36 (5.6%) had hybrid procedures combining endovascular coiling with laparoscopic splenic artery ligation. Indication for treatment was based on vessel tortuosity, landing zones, and the presence of side branches supplying end organs. Early outcomes were favorable regardless of treatment strategies. A single organ-related complication was reported (1/36, 2.8%) following open/endovascular repair, consisting of mild pancreatitis, which resolved with conservative management. No perioperative or aneurysm-related deaths were reported in any of the included cases. No recurrent aneurysms or late aneurysm-related complications were described during the reported follow-up intervals (mean ≈ 10.5 months, range 1.5-42 months). Conclusions: Aneurysms arising from aberrant visceral arteries present unique challenges because their origin, course, and collateral networks deviate from standard anatomy. Patient selection and detailed anatomic mapping preoperatively are decisive as inadequate imaging or failure to recognize an aberrant origin can lead to the incomplete exclusion or inadvertent sacrifice of critical branches. Understanding the anatomy of visceral arteries and their variations is paramount in clinical practice, particularly when planning interventions for minimizing procedural risks, optimizing outcomes, and preventing potential complications. Contemporary practice favors endovascular repair due to lower perioperative morbidity, but success depends on vessel tortuosity, landing zones, and the presence of important side branches that supply end organs.

OA18 A rare presentation of Polyarteritis Nodosa

Homeotherms are substantially more capable of resisting cold than heat, if the normal rectal temperature is taken as the point of departure. With the possible exception of man, the number and effectiveness of the mechanisms protecting against loss of heat are also far greater. In contrast to the poikilotherms, whose temperature resistance can be essentially characterized by their lethal temperatures, a number of critical temperature ranges can be distinguished for homeotherms: 1. the external temperature at which the capacity for temperature regulation is exceeded and the core temperature changes; 2. the core temperature at which the regulatory centers are paralyzed and 3. the lethal temperature. Special conditions are also found, in which local temperature damage takes place while overall temperature regulation is maintained. Accordingly, the tolerance shown by homeotherms for extreme temperatures is determined by the interaction of a large number of factors.

Lipoma arborescens is a rare, benign intra-articular hyperplastic tumor characterized by villous, polypoidal, and lipomatous proliferation of the synovium. The knee is the most commonly affected joint1,2. Intra-articular lipoma arborescens is rare in adults3-7 and extremely rare in children5,8-11. The disease is typically considered to be a unilateral condition, and bilateral disease has been reported to be extremely rare, especially in children8-13. Patients usually present with chronic or recurrent painless swelling of the knee joint. Lipoma arborescens must be considered in the differential diagnosis of chronic joint effusions in childhood10. Our patient and his family were informed that data concerning the case would be submitted for publication, and they consented. A thirteen-year-old boy was admitted to our hospital because of chronic pain in the left knee. He had no history of trauma or infection. The left knee had been painful for four weeks during walking and running, thus limiting his daily activities. There were no locking symptoms. The patient’s medical history and the family history were unremarkable. The boy was healthy and had a body mass index of 21 kg/m2. Physical examination revealed bilateral swelling of the knee joints. Both knees had a normal local temperature and normal skin coloration and were not tender to palpation. Both joints were more voluminous than expected, and a mild joint effusion was present bilaterally. Full extension and 140° of flexion were possible in both knees, and knee motion did not elicit pain. There was no tissue mass around the knees, and no laxity could be detected. The results of blood tests, including measurements of the erythrocyte sedimentation rate, rheumatoid factor, C-reactive protein level, histocompatibility antigen B27 (HLA-B27), and antinuclear immunoglobulin, were normal. …

Sarcoidosis is a noncaseating granulomatous disease, likely of autoimmune etiology, that causes inflammation and tissue damage in multiple organs, most commonly the lung, but also skin, and lymph nodes. Reduced dendritic cell (DC) function in sarcoidosis peripheral blood compared with peripheral blood from control subjects suggests that blunted end organ cellular immunity may contribute to sarcoidosis pathogenesis. Successful treatment of sarcoidosis with tumor necrosis factor (TNF) inhibitors, which modulate DC maturation and migration, has also been reported. Together, these observations suggest that DCs may be important mediators of sarcoidosis immunology. This review focuses on the phenotype and function of DCs in the lung, skin, blood, and lymph node of patients with sarcoidosis. We conclude that DCs in end organs are phenotypically and functionally immature (anergic), while DCs in the lymph node are mature and polarize pathogenic Th1 T cells. The success of TNF inhibitors is thus likely secondary to inhibition of DC-mediated Th1 polarization in the lymph node.

Nanomedications can be carried by blood borne monocyte-macrophages into the reticuloendothelial system (RES; spleen, liver, lymph nodes) and to end organs. The latter include the lung, RES, and brain and are operative during human immunodeficiency virus type one (HIV-1) infection. Macrophage entry into tissues is notable in areas of active HIV-1 replication and sites of inflammation. In order to assess the potential of macrophages as nanocarriers, superparamagnetic iron-oxide and/or drug laden particles coated with surfactants were parenterally injected into HIV-1 encephalitic mice. This was done to quantitatively assess particle and drug biodistribution. Magnetic resonance imaging (MRI) test results were validated by histological coregistration and enhanced image processing. End organ disease as typified by altered brain histology were assessed by MRI. The demonstration of robust migration of nanoformulations into areas of focal encephalitis provides '"proof of concept" for the use of advanced bioimaging techniques to monitor macrophage migration. Importantly, histopathological aberrations in brain correlate with bioimaging parameters making the general utility of MRI in studies of cell distribution in disease feasible. We posit that using such methods can provide a real time index of disease burden and therapeutic efficacy with translational potential to humans.

Bcl‐2 family proteins regulate mitochondrial apoptosis and have been shown to be involved in a variety of diseases. In sepsis, systemic inflammatory response to pathogens, apoptosis is triggered in immune cells as a result of the cytokine storm induced by sepsis. Immune cell death is not the only damage caused by sepsis and the mechanism of cellular injury on end organs is unknown despite advances in modern medicine. Much of the mortality associated with sepsis is a result of end organ failure, particularly the kidneys. Research has shown that a small amount of apoptotic cell death is characteristic in acute renal injury associated with sepsis, thus Bcl‐2 family proteins should be involved in renal death as a result of septic shock. Use of a two‐step cell culture model stresses immune cells to stimulate cytokine release comparable to the cytokine storm found in sepsis, which can then be harvested and used to treat cultured kidney cells to induce death. Examination of Bcl‐2 proteins after treatment with stimulated cytokines showed a decrease in cell viability; an increase of BH3 only, pro‐apoptotic proteins; and a decrease in anti‐apoptotic Bcl‐2 confirming their hypothesized involvement. Results provide hope for elucidation of the mechanism of sepsis from which more efficient treatments can be developed. Research funded by Elon University URP, Department of Chemistry, Elon College Fellows, and the Provost Award to VDGM.