Normal Skin Temperature Research Articles

Human behavior in different TDRAs

Operative temperature is a synthesis index for radiant temperature and air temperature. The objective of this paper was to investigate human behavior in the environment that the temperature difference between radiant and air temperature (TDRA) was 0, 5, 8 and 10°C. The four types of TDRA were controlled in two operative temperatures, 28 and 32°C. The skin temperatures, thermal sensation vote (TSV) and thermal comfort vote (TCV) were recorded. The results showed that when TDRA was 0–5°C, the mean skin temperature (MST) had no change, and the local skin temperature (LST) had little change except for face and upper arm. However, when TDRA was above 5°C, the MST and LST decreased with the increment of TDRA. During the whole course that TDRA increased from 0 to 10°C, the thermal sensation changed from warm to cool. So in high radiant temperature, human body could keep normal skin temperature and thermal comfort by decreasing air temperature. The conclusions were significant for the physiological behavior of human.

Is touch gating due to sensory or cognitive interference?

Touch gating, the attenuation of tactile sensitivity in the presence of pain, is a well-documented phenomenon, but its mechanism is unknown. The ability of pain to capture attention suggests that touch gating may be an example of distraction, but the fact that pain raises tactile but not auditory thresholds argues that touch gating is a form of somatosensory interaction. Therefore, the present study was carried out to determine whether touch gating is the result of sensory or cognitive interference. Touch gating was repeatedly produced by delivering a colocalized painful heat stimulus (45°C) during forced-choice measurements of vibration threshold on the palm. Noxious heat significantly increased thresholds compared with those measured at normal skin temperature, and this interference did not decline over the course of an extended series of experiments during which pain intensity significantly habituated. Touch gating was thus related to the constant physical intensity, rather than to the changing subjective intensity, of the noxious stimulus. For comparison, a form of unambiguously cognitive interference, the Stroop effect, was also measured repeatedly; it declined significantly across sessions, unlike touch gating interference. Finally, touch gating was not correlated with measures of participants’ distractibility, fear of pain, hypervigilance, or anxiety, variables previously found to influence pain on a cognitive level. Taken together, the results suggest that touch gating is a robust, stimulus-locked form of sensory interaction, rather than a transitory result of distraction or other cognitive processes.

Hypoalgesia in mice lacking aquaporin-4 water channels

Previous studies have demonstrated the involvement of astrocytes in the modulation of pain. The water channel aquaporin-4, which is expressed in astrocytes but not neurons, has also been demonstrated to function in sensory processing, including hearing, vision, and olfaction. In the present study, we investigated a possible role of aquaporin-4 in the processing of nociception by measuring behavioral responses to noxious stimulation in aquaporin-4 knockout mice. Pain thresholds were increased in knockout mice, when compared to wild-type mice, with thermal and chemical stimulation but not mechanical stimulation. Aquaporin-4 knockout mice presented normal locomotor activity and basal skin temperature. Likewise, the electrophysiological recordings showed a significant decrease in the number of dorsal horn neurons sensitive to noxious thermal stimuli in aquaporin-4 knockout mice. Moreover, latencies to thermal stimuli were significantly prolonged in a subset of dorsal horn wide-dynamic-range neurons. Taken together, these results suggest that aquaporin-4 plays a role in the processing of nociception.

Transdermal delivery of fentanyl from matrix and reservoir systems: Effect of heat and compromised skin

The United States Food and Drug Administration (FDA) has received numerous reports of serious adverse events, including death, in patients using fentanyl transdermal systems (FTS). To gain a better understanding of these problems, the current research focuses on the in vitro characterization of fentanyl reservoir (Duragesic®) and matrix (Mylan) systems with respect to drug release and skin permeation under conditions of elevated temperature and compromised skin. In addition, different synthetic membrane barriers were evaluated to identify the one that best simulates fentanyl skin transport, and thus may be useful as a model for these systems in future studies. The results indicate that reservoir and matrix FTS are comparable when applied to intact skin at normal skin temperature but the kinetics of drug delivery are different in the two systems. At 40°C, the permeation rate of fentanyl was twice that seen at 32°C over the first 24 h in both systems; however, the total drug permeation in 72 h is significantly higher in the reservoir FTS. When applied to partially compromised skin, matrix FTS has a greater permeation enhancement effect than reservoir FTS. The intrinsic rate limiting membrane of the reservoir system served to limit drug permeation when the skin (barrier) permeability was compromised. Different ethylene vinyl acetate membranes were shown to have fentanyl permeability values encompassing the variability in human skin. Results using the in vitro model developed using synthetic membranes suggest that they mimic the effect of compromised skin on fentanyl permeability. Especially for highly potent drugs such as fentanyl, it is important that patients follow instructions regarding application of heat and use of the product on compromised skin. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2357–2366, 2010

Exercise Induced Swelling And Neurologic Symptoms-Women's Lacrosse

HISTORY: 21year-old female freshman college lacrosse player, with pmh of right shoulder multi-directional instability secondary to Ehlers-Danolos, presents with a three week history of right arm swelling, discoloration, and numbness during jogging. Starting in fall 2009, the patient complained of right arm swelling, numbness, and pallor during jogging. The patient could feel her right shoulder subluxing while jogging. After jogging for 15 minutes she would start having numbness and tingling in her arm. She also noted hand swelling and discoloration. The patient was evaluated with right shoulder instability during her pre-participation physical examination. She failed a rehabilitation program so underwent an arthroscopic capsulorrhapy and Bankart repair of the anterior and posterior labrum during her sophomore year. She continued to have multiple subluxations. A consulting orthopedic surgeon determined that her shoulder laxity was secondary to Ehlers-Danlos. She was tested by a geneticist who confirmed the diagnosis. PHYSICAL EXAM: Mild tenderness of the anterior and posterior capsule. Positive sulcus sign bilaterally. Equal radial and brachial pulses. No peripheral arm edema. Nor No peripheral arm edema. Normal skin color and temperature. Strength of the upper extremity 5/5. Sensation to pinprick intact. Biceps, triceps, and brachioradialis reflexes 2+. DIFFERENTIAL DIAGNOSIS: Complex regional pain syndrome Axillary artery aneurysm or occlusion Tumor (mass effect) Raynaud's phenomenon Vascular etiology-arterial/venous/mixed TESTS AND RESULTS: Segmental wrist brachial index: Left and right arm is normal. Upper Extremity Thoracic Outlet Study: Abnormal during 7 lb weight maneuver in the right extremity. The left extremity is normal. FINAL WORKING DIAGNOSIS: Exercise induced thoracic outlet syndrome TREATMENT AND OUTCOMES: Patient was cleared to play given the understanding that participating in lacrosse has the risk of recurrent right shoulder subluxations, long term nerve injury to the brachial plexus, and vascular injury because of repetitive damage. Physical therapy for shoulder girdle strengthening

Success of acupuncture treatment in patients with initially low sperm output is associated with a decrease in scrotal skin temperature

Poor spermatogenesis in patients with inflammation of the genital tract is associated with scrotal hyperthermia. These patients can benefit from acupuncture treatment. We conducted a study to verify whether the influence of acupuncture treatment on sperm output in patients with low sperm density is associated with a decrease in scrotal temperature. The experimental group included 39 men who were referred for acupuncture owing to low sperm output. The control group, which comprised 18 normal fertile men, was used to define a threshold (30.5 degrees C) above which scrotal skin temperature was considered to be high. Accordingly, 34 of the 39 participants in the experimental group initially had high scrotal skin temperature; the other five had normal values. Scrotal skin temperature and sperm concentration were measured before and after acupuncture treatment. The five patients with initially normal scrotal temperatures were not affected by the acupuncture treatment. Following treatment, 17 of the 34 patients with hyperthermia, all of whom had genital tract inflammation, had normal scrotal skin temperature; in 15 of these 17 patients, sperm count was increased. In the remaining 17 men with scrotal hyperthermia, neither scrotal skin temperature nor sperm concentration was affected by the treatment. About 90% of the latter patients suffered from high gonadotropins or mixed etiological factors. Low sperm count in patients with inflammation of the genital tract seems to be associated with scrotal hyperthermia, and, consequently, acupuncture treatment is recommended for these men.

Malignant hyperthermia in children

Malignant hyperthermia is a rare disease which is mainly an inherited autosomal dominant trait. It is characteristic for muscle rigidity, metabolism or respiratory acidosis, high values of serum creatine kinase. Then appears myoglobinuria which can lead to tubular necrosis and acute renal failure. The male child, ten years old, hospitalized because of the high temperature, exhaustion and cough. On the second day of hospitalization, he has hyperthermia (39.8 degrees C), dyspnoea, tachypnoea, was somnolent, occasionally raving, exhausted with the pains in the muscles which were rigid and painfully sensitive. During the night, the urine was dark red, but the diuresis was well. The next day, laboratory analyses showed high values of aspartate aminotransferase (4263 IU/l), alanine aminotransferase (1311 IU/l), lactate dehydrogenase (11787 IU/l), while the values of serum creatine kinase were so high that they could not be registered. The urine analysis showed the negative result on gall colours and haematuria and positive on myoglobin. During the following days, the patient had normal skin temperature, the pains in the muscles were gradually weakened and the urine cleared up. On the third day, the value of creatine kinase was measured and it was 178700 IU/l. During the next two weeks, the clinical finding was gradually normalized while the laboratory values of serum enzyme were gradually normalized only in twenty days. Malignant hyperthermia is a serious clinical syndrome which can be found with, until then, a clinically healthy child (without chronic myopathy) and it appears with the high temperature or during the surgical interventions with anaesthetics, which is especially dangerous.

Difficult Airway Due To Large Scalp Swelling In Occipital Region

A 24-year-old male presented with a big scalp swelling in the occipital region since birth, which was initially small and increased to present size of 15×10×7 cm. The swelling was lobulated, non-mobile, non-tender, with normal skin temperature and of different consistency. There was no discharge from the swelling. The aspirate from the swelling showed features of mesenchymal tumor of pleomorphic type.

Medial Knee Pain - Recreational Swimmer

HISTORY: A 42-year-old male physician and recreational swimmer presented with right knee pain. He had presented with right knee pain 1 year earlier after he slipped carrying a box, fell, and hyperflexed his knee. At that time he had minimal swelling, VMO pain, and was limited by pain with walking, squatting, or sitting with his knees bent. He complained of instability of the knee and tenderness to the medial joint line. MRI at that time revealed medial meniscus tear. He underwent arthroscopy for partial medial menisectomy of the posterior horn. Afterwards, his joint line pain resolved, but he continued to have pain localized to the VMO region with numbness and burning. Symptoms were constant, aching, and worsened by whip-kick motion with breast stroke, standing, knee bending, biking, and resting a portable computer on this area. He noted no skin rash, mottling, or temperature change. PHYSICAL EXAM Right knee with full ROM. Quad atrophy, including right VMO being slightly smaller than left. No palpable mass. No tenderness at VMO quadriceps or patellar tendon insertion, but tender over the VMO 1 inch from the insertion. Normal lower extremity reflexes. Decreased sensation along the medial knee from the joint line up to 10 cm proximal. Positive Tinel's sign at the adductor canal. Positive saphenous nerve stretch test. Lower extremity strength is 5/5 and equal. Plica band not palpable. No tenderness of the medial patellafemoral ligament, medial joint line, medial femoral condyle, or patella. Negative grind, Clark's sign, and lateral apprehension. Negative McMurray's. Lachman's and posterior drawer were normal. Varus and valgus stress were normal. Normal posterior tibialis pulse. Normal skin color and temperature. Arthroscope portal scars present, but not near the location of symptoms. DIFFERENTIAL DIAGNOSIS VMO tendinosis, saphenous nerve entrapment soft tissue or bone tumor (osteochondroma) lumbar radiculopathy (L3/L4) TESTS AND RESULTS Previous MRI knee – medial meniscus tear Knee Radiographs, 4 view – normal MRI thigh – normal FINAL WORKING DIAGNOSIS Saphenous Nerve Entrapment TREATMENT AND OUTCOMES Traditional PT and Augmented Soft Tissue Molibization 50% improvement, still restricted in activity of daily living. Steriod Injection at the Adductor Canal Marked immediate relief of symptoms, but minimal long-term improvement. Surgical consultation Neurontin/NSAIDS for conservative management. Some benefit, but patient elected saphenous nerve decompression. Operative findings included an area of serous fluid and pale area of nerve consistent with compression at the adductor canal. After the adductor canal was released his symptoms resolved.

Doppler sonographic assessment of posttraumatic reflex sympathetic dystrophy.

To reveal the arterial Doppler sonographic findings in cases of posttraumatic reflex sympathetic dystrophy Eleven patients had hand reflex sympathetic dystrophy, and 9 had foot reflex sympathetic dystrophy. The duration of symptoms ranged from 1 to 28 weeks, and the history of fracture ranged from 6 to 48 weeks. Bilateral brachial or popliteal arteries proximal to injuries were evaluated by Doppler sonography with a 7.5-MHz linear transducer. All patients also had triphasic bone scintigraphy and extremity thermography Two patients had monophasic waveforms and 4 had low-pulsatility triphasic waveforms on the affected limbs when compared with the asymptomatic limbs. All opposite asymptomatic limbs had normal triphasic waveforms in these 6 cases. Spectral analysis revealed a loss or decrease of a normal reversed flow component with a reduced pulsatility index on the affected limb. Fourteen other patients had symmetric triphasic waveforms. We observed that the patients who had stage 1 reflex sympathetic dystrophy and warm limbs with durations of symptoms of more than 2 weeks had positive Doppler sonographic findings, whereas all patients with stage 2 reflex sympathetic dystrophy and all with normal skin temperature, regardless of stage, had normal waveforms. Doppler sonography revealed loss of normal triphasic arterial waveforms in some of the cases of stage 1 disease, whereas many cases of stage 1 disease and all cases of stage 2 disease had normal findings. Therefore, we think that Doppler sonography cannot be used for the diagnosis of reflex sympathetic dystrophy but may help in assessing hemodynamic stages of the disease.

Reductions in Systemic and Skeletal Muscle Blood Flow and Oxygen Delivery Limit Maximal Aerobic Capacity in Humans

A classic, unresolved physiological question is whether central cardiorespiratory and/or local skeletal muscle circulatory factors limit maximal aerobic capacity (VO2max) in humans. Severe heat stress drastically reduces VO2max, but the mechanisms have never been studied. To determine the main contributing factor that limits VO2max with and without heat stress, we measured hemodynamics in 8 healthy males performing intense upright cycling exercise until exhaustion starting with either high or normal skin and core temperatures (+10 degrees C and +1 degrees C). Heat stress reduced VO2max, 2-legged VO2, and time to fatigue by 0.4+/-0.1 L/min (8%), 0.5+/-0.2 L/min (11%), and 2.2+/-0.4 minutes (28%), respectively (all P<0.05), despite heart rate and core temperature reaching similar peak values. However, before exhaustion in both heat stress and normal conditions, cardiac output, leg blood flow, mean arterial pressure, and systemic and leg O2 delivery declined significantly (all 5% to 11%, P<0.05), yet arterial O2 content and leg vascular conductance remained unchanged. Despite increasing leg O2 extraction, leg VO2 declined 5% to 6% before exhaustion in both heat stress and normal conditions, accompanied by enhanced muscle lactate accumulation and ATP and creatine phosphate hydrolysis. These results demonstrate that in trained humans, severe heat stress reduces VO2max by accelerating the declines in cardiac output and mean arterial pressure that lead to decrements in exercising muscle blood flow, O2 delivery, and O2 uptake. Furthermore, the impaired systemic and skeletal muscle aerobic capacity that precedes fatigue with or without heat stress is largely related to the failure of the heart to maintain cardiac output and O2 delivery to locomotive muscle.

Effects of epidural anesthesia on thermal sensation

Background and Objectives: Epidural anesthesia decreases the core temperatures triggering vasoconstriction and shivering, presumably by increasing apparent (as opposed to actual) lower-body temperature. We therefore tested the hypothesis that epidural anesthesia also increases the overall perception of warmth. Methods: We studied 8 volunteers in a randomized, cross-over protocol separated by at least 48 hours. On one day, epidural anesthesia was induced to a T11 sensory level; the other day was a control without anesthesia. Core temperature and upper-body skin temperatures (33[deg ]C) were kept constant throughout. Lower-body skin temperature was set in a random order to 31[deg ]C, 32[deg ]C, 33[deg ]C, 34[deg ]C, 35[deg ]C, and 36[deg ]C and maintained by circulating water and forced air. At each temperature, the volunteers rated their thermal sensation with a visual analog scale (0 = cold, 100 = hot). Core temperature was 36.8 [plusmn] 0.1[deg ]C on the control day and 36.7 [plusmn] 0.1[deg ]C on the epidural day. Results: Scores for thermal sensation on the epidural day were near 47 mm at each lower-body skin temperature. On the control day, visual analog scores at a lower-body skin temperature of 31[deg ]C were 16 [plusmn] 10 mm and increased linearly to 61 [plusmn] 6 mm at 36[deg ]C. Control thermal sensation scores thus equaled those during epidural anesthesia when lower-body skin temperature was near 34[deg ]C. Conclusions: Thermal sensation with and without epidural anesthesia was comparable at a lower-body temperature near 34[deg ]C, which is a normal leg skin temperature. This suggests that autonomic and behavioral thermoregulatory consequences of epidural anesthesia differ[mdash ]or that the current explanation for reduced vasoconstriction and shivering thresholds during epidural anesthesia is incorrect. Reg Anesth Pain Med 2001;26:527-531.

Thermal imaging in acute herpes zoster or post-zoster neuralgia.

Asymmetry of normal skin temperature patterns has been reported in patients with herpetic disorders. The aim of the study was to describe the temperature distribution in patients suffering from acute herpes zoster or post-herpetic neuralgia. Biographic data, including age, gender and time of onset of the skin lesions, were recorded. The distribution of pain was investigated by pain mapping, and the intensity of pain and dysesthesia was quantified by a visual analogue scale. Infrared thermal images of the affected body regions were performed in all possible views using either an Agema 870 or a NEC San-ei Thermotracer. The mean temperature difference between the affected and the unaffected sides of the body in all patients was 0.52+/-0.30 degrees C. Higher temperatures were detected in early cases with a disease duration of 1-9 days (mean temperature difference: 0.62+/-0.36 degrees C) than in patients with pain scores greater than 79 (mean temperature difference: 0.48+/-0.33 degrees C). Only 6 of 57 patients presented with a temperature difference between the affected side and contralateral side of less than 0.2 degrees C. Thermal asymmetry of the skin is a common finding in patients with acute herpes. However, the thermal patterns seem to correlate better with the duration of the disease than with the intensity of pain.

Basic Science (32)

Involvement of the proinflammatory cytokines tumor necrosis factor‐alpha, IL‐1 beta, and IL‐6 but not IL‐8 in the development of heat hyperalgesia: effects on heat‐evoked calcitonin gene‐related peptide release from rat. (Friedrich‐Alexander‐Universität Erlangen‐Nürnberg, Erlangen, Germany) J Neurosci 2000;20:6289–6293.In this study, the rat skin model was used to investigate the effects of proinflammatory cytokines on the basal and heat‐evoked release of calcitonin gene‐related peptide (CCRP) from nociceptors in vivo. In contrast to the excitatory effects of cytokines observed in vivo, none of the cytokines tested evoked any CCRP release at normal skin temperature of 32°C. However, the cytokines IL‐1β, tumor necrosis factor (TNF)‐α, and IL‐6 but not IL‐8 induced a pronounced and transient sensitization of the heat‐evoked CGRP release from nociceptors in vitro. This heat sensitization was dose dependent, with EC50 for IL‐1β of 2.7 ng/mL and for TNF‐α of 3.1 ng/mL. The maximum IL‐1β effect reached almost 600% of the heat‐evoked release, and the maximum TNF‐α effect induced a rise in CGRP release of 350%. In contrast to IL‐1β and TNF‐α, IL‐6 did not induce heat sensitization when applied alone, but was only effective in the presence of soluble IL‐6 receptor. This suggests a constitutive expression of signaling receptors for TNF and IL‐1β and the signal transduction molecule gp 130, but not IL‐6 receptor or IL‐8 receptor. Furthermore, the acute cytokine signaling observed was independent of transcriptional pathways because sensitization occurred on short latency in vitro and under conditions that excluded chemotactic accumulation of immune cells from blood vessels. Conclude that interleukins may play an important role in the initiation of heat hyperalgesia in inflammation and neuropathy. Comment by Marshall Devor, PhD.Impulses in nociceptive afferents signal pain to a conscious brain, but in addition, they have an efferent, effector role in peripheral tissue. Specifically, impulses arriving at a sensory ending may cause the release of various peptides and other potential inflammatory mediators, affecting local tissue circulation and the trophic state of the tissue. Oprée and Kress show that specific cytokines can facilitate this release by lowering the temperature required to evoke release of the calcitonin gene‐related peptide. If the temperature required were lowered to basal tissue temperature, a real possibility, then the peptides would be released on a tonic basis at normal body temperature. This could be a mechanism for the disruption of normal tissue integrity in chronic inflammatory conditions such as rheumatoid arthritis.

Involvement of the Proinflammatory Cytokines Tumor Necrosis Factor-α, IL-1β, and IL-6 But Not IL-8 in the Development of Heat Hyperalgesia: Effects on Heat-Evoked Calcitonin Gene-Related Peptide Release from Rat Skin

Proinflammatory cytokines contribute to the development of inflammatory and neuropathic pain and hyperalgesia in many in vivo models. The rat skin model was used to investigate the effects of proinflammatory cytokines on the basal and heat-evoked release of calcitonin gene-related peptide from nociceptors in vitro. In contrast to the excitatory effects of cytokines observed in vivo, none of the cytokines tested evoked any calcitonin gene-related peptide (CGRP) release at normal skin temperature of 32 degrees C. However, the cytokines IL-1beta, tumor necrosis factor (TNF)-alpha, and IL-6 but not IL-8 induced a pronounced and transient sensitization of the heat-evoked CGRP release from nociceptors in vitro. This heat sensitization was dose dependent, with EC(50) for IL-1 beta of 2.7 ng/ml and for TNF-alpha of 3.1 ng/ml. The maximum IL-1 beta effect reached almost 600% of the heat-evoked release, and the maximum TNF-alpha effect induced a rise in CGRP release of 350%. In contrast to IL-1 beta and TNF-alpha, IL-6 did not induce heat sensitization when applied alone but was only effective in the presence of soluble IL-6 receptor. This suggests a constitutive expression of signaling receptors for TNF and IL-1 beta and the signal transduction molecule gp130 but not IL-6 receptor or IL-8 receptor. Furthermore, the acute cytokine signaling observed in the present study was independent of transcriptional pathways because sensitization occurred on short latency in vitro and under conditions that excluded chemotactic accumulation of immune cells from blood vessels. Our results demonstrate that interleukins may play an important role in the initiation of heat hyperalgesia in inflammation and neuropathy.

THERMOGRAPHIC STUDY OF LOW LEVEL LASER THERAPY FOR ACUTE-PHASE INJURY

Acute-phase injury is generally treated by localized cooling of the region, and rarely by the active use of low level laser therapy (LLLT) in Japan. Thermographic studies of acutephase injury revealed that circulatory disturbances at the site of trauma occurred due to swelling and edema on the day following the injury, and that skin temperature was high at the site of the trauma and low at the periphery. Following LLLT, circulatory disturbances rapidly improved, while temperature in the high temperature zone around the site of trauma fell by 3 degrees on the average, but at the periphery the low temperature rose by 3 degrees on the average to nearly normal skin temperature. Clinically, swelling and edema improved. LLLT was also useful in treating necrosis of the skin in the wound area and in accelerating healing of surgical wounds of paralytic feet, which are prone to delayed, wound healing and also wounds due to spoke injury. LLLT is useful in treating swelling and edema in acutephase injury and in accelerating healing of surgical wounds.

Dynamic thermography: analysis of hand temperature during exercise.

Exercise has a noted effect on skin blood flow and temperature. We aimed to characterize the normal skin temperature response to exercise by thermographic imaging. A study was conducted on ten healthy and active subjects (age=25.8+/-0.7 years) who were exposed to graded exercise for determination of maximal oxygen consumption (VO2 max), and subsequently to constant loads corresponding to 50%, 70%, and 90% of VO2 max. The skin temperature response during 20 min of constant load exercise is characterized by an initial descending limb, an ascending limb and a quasi-steady-state period. For 50% VO2 max, the temperature decrease rate was - 0.0075+/-0.001 degrees C/s during a time interval of 390+/-47 s and the temperature increase rate was 0.0055+/-0.0031 degrees C/s during a time interval of 484+/-99 s. The level of load did not influence the temperature decrease and increase rates. In contrast, during graded load exercise, a continuous temperature decrease of -0.0049+/-0.0032 degrees C/s was observed throughout the test. In summary, the thermographic skin response to exercise is characterized by a specific pattern which reflects the dynamic balance between hemodynamic and thermoregulatory processes.

Modes of action of terpene penetration enhancers in human skin; Differential scanning calorimetry, small-angle X-ray diffraction and enhancer uptake studies

The mechanisms through which the terpenes, d-limonene, 1–8-cineole and nerolidol, increase the permeability of human stratum corneum (s.c.) and the mechanisms underlying propylene glycol (PG)/terpene synergy were investigated using differential scanning calorimetry (DSC), small-angle X-ray diffraction (SAXD) and enhancer uptake studies. DSC experiments identified two major lipid transitions at 72° and 83°C. d-Limonene reduced the temperatures of both transitions by approx. 20°C without affecting their enthalpies ( ΔH). 1–8-Cineole also reduced the temperatures of both transitions by approx. 20°C but also reduced ΔH for the first major lipid transition; ΔH for the second was unaffected. d-Limonene increased the combined entropy change ( ΔS) associated with both lipid transitions by 11% whereas 1–8-cineole decreased ΔS by 32%. The decrease in ΔS produced by 1–8-cineole provides evidence that this enhancer is lipid disruptive at normal skin temperature. Nerolidol reduced the transition temperatures of both major lipid transitions by approx. 4°C and also decreased their cooperativity. Reduced bilayer cooperativity indicates that this enhancer also disrupts the intercellular lipids. Lack of a clear baseline prevented accurate measurement of ΔH and ΔS values following nerolidol treatment. SAXD experiments showed that d-limonene and 1–8-cineole act to reduce the intensity of lipid based reflections. Decreases in reflection intensities may be linked to a disruption of lipid packing within the bilayers and/or to a disturbance in the stacking of the bilayers. Treatment with nerolidol did not markedly reduce the intensities of the bilayer based reflections. Uptake studies revealed that large quantities of terpenes can be accommodated by the s.c. (mean uptake of d-limonene, 1–8-cineole and nerolidol was 8.90%, 26.2% and 39.6% w/w dry s.c.). The possibility that terpene enhancers pool in the s.c. is discussed. DSC and SAXD investigations provided fragmented evidence that PG/terpene synergy may produce enhanced lipid bilayer disruption. Enhancer uptake studies showed that PG does not significantly increase terpene delivery to the s.c. above that provided by application of neat terpenes.

Characterization of Low-Temperature (i.e.,

This study aims to characterize human stratum corneum (SC), focusing on those lipid transitions that occur at or below physiologically relevant temperatures. In the past, a lipid transition near 35 degrees C had been thought to be variable and a consequence of superficial sebaceous lipid contamination. However, analysis here indicates that it is widely present, and cannot be attributed to sebum production. We demonstrate that this transition represents a solid-to-fluid phase change for a discrete subset of SC lipids. The reversibility of this transition upon reheating, and its absence in extracted lipid samples imply that these lipids are not uniformly present throughout the SC, but would appear to be differentially distributed in response to terminal differentiation. Further, such an arrangement could involve a close association with other nonlipid (e.g., protein) components. Evidence for a new transition at approximately 55 degrees C is presented that suggests the loss of crystalline orthorhombic lattice structure. The existence of orthorhombic structure at physiologic temperature is reasoned to involve ceramides and/or free fatty acids. Localization of these lipids at the level of the corneocyte envelope supports a comprehensive picture of water transport across the SC, whereby diffusion occurs primarily via the intercellular lipids. This view, coupled with the hydration-induced changes in lipid disorder observed here provides additional insight into the mechanism by which skin occlusion increases permeability. Summarily, these results i) emphasize the inherent danger of over-interpreting experiments with isolated SC lipids, ii) emphasize the potential advantage(s) of employing several biophysical techniques to study SC structure, and iii) indicate that a full characterization of lipid phase behavior is requisite to our eventual understanding of SC structure and permeability function, particularly those phase transitions that occur near or at normal skin temperature.

Percutaneous local anaesthesia: drug release characteristics of the amethocaine phase-change system

Differential scanning calorimetry has been used to demonstrate that amethocaine base, when formulated as a percutaneous anaesthetic gel, undergoes a phase change at or below normal skin temperature. Under aqueous conditions the melting point of amethocaine was lowered by approx. 10°C. The influence of the phase change on drug release characteristics was investigated in respect of both gelled, saturated amethocaine solutions and formulations containing a reservoir of undissolved drug. Drug release from the formulation, and subsequent penetration of iipophilic barriers, was shown to proceed from the aqueous diffusion layer at the formulation/barrier membrane interface. A more rapid replenishment of the diffusion layer can be achieved after the phase change has occurred. Under these conditions the drug is present both in solution and as undissolved oil droplets, the latter having an enhanced dissolution rate compared to solid drug particles in suspension. Given the low solubility of amethocaine base, and therefore the comparatively low concentration gradient established across the diffusion layer, the proven percutaneous anaesthetic efficacy of amethocaine is largely related to its lipophilicity and anaesthetic potency. An overall scheme is proposed for the drug release characteristics of the amethocaine phase-change system.