Scratch Cycle Research Articles

IGFBP1 promotes the proliferation and migration of lung adenocarcinoma cells through the PPARα pathway

BackgroundThe immune status is closely linked to cancer progression, metastasis, and prognosis. Lipid metabolism, crucial for reshaping immune status, plays a key role in regulating the advancement of lung adenocarcinoma (LUAD) and deserves further investigation. MethodsThis study classifies LUAD patients into different immune subtypes based on lipid metabolism-related genes and compares the clinical characteristics among these subtypes. Single-multi COX analysis screens out key genes related to prognosis, and a risk feature and prognostic model are constructed. Cell cloning, scratch, transwell, western blotting and flow cytometry cell cycle analysis to detect the function of key genes. A subcutaneous tumor animal model is used to investigate the in vivo function and molecular mechanisms of key genes. ResultsLUAD patients are classified into three immune subtypes, among which C3 subtype has lower immune status and higher frequency of gene mutations, and show lower immunoreactivity in immunotherapy. COX analysis identified a prognostic model for four lipid metabolism factors (IGFBP1, NR0B2, PPARA, and POMC). IGFBP1, a core gene in this model, is highly expressed in the C3 subtype. Functionally, knocking down IGFBP1 significantly inhibits tumor cell cloning, scratch, and migration abilities, and downregulates the expression of cell cycle and EMT-related proteins. Knocking down IGFBP1 significantly inhibits tumor burden (P < 0.05). Mechanistically, knocking down IGFBP1 inhibits the activation of PPARα to regulate tumor cell growth. ConclusionsThis study found that lipid metabolism genes are closely related to LUAD, and IGFBP1 may be a key gene in regulating tumor growth and development.

Bioinformatics analysis and experimental validation reveal that CDC20 overexpression promotes bladder cancer progression and potential underlying mechanisms.

Bladder cancer is a prevalent malignancy. CDC20, a pivotal cell cycle regulator gene, plays a significant role in tumour cell proliferation, but its role in bladder cancer remains unclear. This study aimed to analyse CDC20 expression in bladder cancer and explore its roles in tumour progression, treatment response, patient prognosis, and cellular proliferation mechanisms. We systematically analysed CDC20 expression in bladder cancer using bioinformatics. Our study investigated the impact of CDC20 on chemotherapy and radiotherapy sensitivity, patient prognosis, and changes in CDC20 methylation levels. We also explored the role and potential underlying mechanisms of CDC20 in bladder cancer cell growth. We used lentiviral transfection to downregulate CDC20 expression in 5637 and T24 cells, followed by CCK-8, colony formation, scratch, invasion, apoptosis, and cell cycle analyses. CDC20 is highly expressed in bladder cancer and is significantly correlated with poor prognosis. Moreover, CDC20 demonstrated high diagnostic potential for bladder cancer (AUC > 0.9). The tumour methylation levels of CDC20 in tumour tissues markedly decreased compared with those in normal tissues, and lower methylation levels were associated with a worse prognosis. Elevated CDC20 expression is linked to increased mutation burden. Our findings suggested a potential association between high CDC20 expression and resistance to chemotherapy and radiotherapy, as CDC20 expression may impact immune cell infiltration levels. Mechanistic analysis revealed the influence of CDC20 on bladder cancer cell proliferation through cell cycle-related pathways. According to the cell experiments, CDC20 downregulation significantly impedes bladder cancer cell proliferation and invasion, leading to G1 phase arrest. Aberrantly high CDC20 expression promotes tumour progression in bladder cancer, resulting in a poor prognosis, and may also constitute a promising therapeutic target.

396 Rapid, substantial and sustained reduction of itch in adults with atopic dermatitis applying ruxolitinib cream 1.5% (SCRATCH-AD)

Abstract Atopic dermatitis (AD) is a chronic, recurring, highly pruritic inflammatory skin disease. The mechanical injury from scratching contributes to skin inflammation and barrier disruption, exacerbating the itch–scratch cycle, which perpetuates the disease. Ruxolitinib cream is a topical formulation of ruxolitinib, a selective Janus kinase (JAK) 1/JAK2 inhibitor, approved in the USA for the short-term and noncontinuous chronic treatment of mild to moderate AD in patients ≥12 years old whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. In two pivotal phase 3 trials (TRuE-AD1 and TRuE-AD2) in adolescents and adults with AD, ruxolitinib cream 1.5% demonstrated significant improvement in itch vs. vehicle cream, as early as 12 h after initial application. A phase 2, open-label, single-site study (SCRATCH-AD; NCT04839380) was undertaken to further understand the short-term clinical benefits of ruxolitinib cream to control pruritus and reduce disease severity in participants with AD. Participants enrolled in the study were aged 18–65 years with AD for ≥6 months, with chronic itch related to AD for ≥3 months, 1–20% affected body surface area (BSA), Investigator’s Global Assessment (IGA) of ≥2 and a peak pruritus numerical rating scale (PP-NRS) score ≥4 at baseline. Participants applied ruxolitinib cream 1.5% twice daily to all lesions identified at baseline and any new lesions for 28 days. The primary endpoint was change from baseline in PP-NRS at Day 2 (24 h after the first application of ruxolitinib cream). Secondary endpoints included change from baseline in modified PP-NRS (mPP-NRS; current itch intensity) at 15 and 30 min and at 1, 2, 4, 6 and 12 h post-treatment on Day 1, as well as change from baseline in PP-NRS from Days 3 through 29, change from baseline in IGA at Days 8, 15 and 29, and safety. The primary analysis included 46 participants in the modified intent-to-treat population. Median age (range) was 30 (18–64) years; 69.6% were female, and 89.1% were White. At baseline, mean (SD) affected BSA was 9.5% (4.94%), mean (SD) 7-day average PP-NRS score was 6.7 (1.36), mean (SD) pretreatment mPP-NRS score was 6.4 (1.72) and 89.1% had an IGA score of 3. The mean (SD) change from baseline in PP-NRS on Day 2 was –3.4 (1.85). The mean (SD) change from baseline in mPP-NRS at 15 min post-treatment was –2.3 (2.34), peaking at –4.2 (2.12) at 4 h post-treatment and was –3.1 (2.00) at 12 h post-treatment. The mean (SD) change from baseline PP-NRS continued to increase through Day 29 [–5.7 (1.60)]. The mean (SD) changes from baseline in IGA score on Days 8, 15 and 29 were –1.4 (0.73), –2.0 (0.87) and –2.2 (0.90), respectively. Treatment-emergent adverse events (TEAEs) were reported in 15/49 (30.6%) participants (none were serious); one participant had a treatment-related TEAE [grade 1 application site reaction (acne)]. No participant discontinued treatment due to TEAE. Lesional skin treated with ruxolitinib cream 1.5% twice daily showed substantial decrease in transepidermal water loss from a baseline mean (SD) score of 35.0 (17.47) to 13.1 (4.42) over 4 weeks, thus reaching similar levels to the nonlesional skin score of 12.7 (4.56) at Day 29. Participants with AD applying ruxolitinib cream 1.5% experienced rapid, substantial improvement in itch, which was sustained and further improved through 28 days of treatment. Itch reduction was observed as early as 15 min, and peak reduction was observed at 4 h after first cream application. These results further demonstrate the clinical benefits and are consistent with the established data on ruxolitinib cream as an effective, well-tolerated topical treatment for AD.

Research progress on clinical and mechanisms of chronic pruritus with anxiety and depression

Chronic pruritus seriously affects the quality of life of patients, which is closely related to stress, anxiety and depression. Prolonged and repeated pruritus can induce negative emotions such as anxiety and depression, while continued increased negative emotions can also promote exacerbation of pruritus, which drives the itch scratch cycle, thereby further aggravating skin damage. More and more studies have explored the mechanism of pruritus, anxiety and depression. This article mainly reviews the clinical relationship between pruritus and anxiety, depression and the new progress of its possible mechanism, providing reference for the prevention, control and effective treatment of chronic pruritus, anxiety and depression.

Reducing the itchiness associated with atopic dermatitis: results from two long‐term nemolizumab studies

British Journal of DermatologyVolume 186, Issue 4 p. e177-e177 Plain Language Summary Reducing the itchiness associated with atopic dermatitis: results from two long-term nemolizumab studies First published: 04 April 2022 https://doi.org/10.1111/bjd.21071AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Linked Article: Kabashima et al. Br J Dermatol 2022; 186:642–651. Atopic dermatitis is an inflammatory skin condition that affects up to 25% of children and 5% of adults worldwide. Itch is a common symptom of atopic dermatitis. The itch–scratch cycle associated with atopic dermatitis affects sleep and daily activities, and causes extreme distress to patients. Nemolizumab is a new drug that has been shown to reduce the severity of itch when given in combination with topical treatments (treatments that are applied directly to the skin). This study, from Japan, aimed to find out if nemolizumab can continuously reduce itch over a long period of time (more than 1 year). Information obtained from patients enrolled in two clinical trials of nemolizumab was examined. Patients in both trials continued to use their usual skin ointments/creams throughout. We found that nemolizumab was able to reduce itch and the symptoms of eczema for up to 68 weeks. Sleep and quality of life were also improved. Importantly, in the 8 weeks after stopping treatment, most patients did not report acute itchiness or a flare up of their atopic dermatitis. In addition, this study shows that nemolizumab was safe to use over this long treatment period. The results support the long-term use of nemolizumab in patients with atopic dermatitis who have not been able to get adequate relief using topical treatment or oral antihistamines. Volume186, Issue4April 2022Pages e177-e177 RelatedInformation

Racial disparities in mortality among patients with prurigo nodularis: A multi-center cohort study

Racial disparities in mortality among patients with prurigo nodularis: A multi-center cohort study

Gefitinib encapsulation based on nano-liposomes for enhancing the curative effect of lung cancer

ABSTRACT Gefitinib (GEB) is one of the drugs used for patients with epidermal growth factor receptor (EGFR)-positive mutations in non-small cell lung cancer (NSCLC). However, application of GEB is limited by its low water solubility, stability, and utilization rate, especially the side effects while GEB is given by oral. In this study, nanoliposome was used as a carrier to prepare nanoliposome compound drug (GL) by embedding GEB in the nanoliposome perfectly combined with green nontoxic solvent and thin-film dispersion method. The nanoliposome structure was expected to improve the water solubility and biocompatibility of GEB, thus improving the effect of cancer treatment. The surface electronegative nanoliposomes can effectively avoid protein adsorption and prolong the circulation time in vivo. Meanwhile, the ratio of lecithin to cholesterol (LE/CH) was explored to maximize the encapsulation efficiency of nanoliposome. Subsequent test results showed that GL exhibited better stability, smaller particle size and higher encapsulation efficiency. In addition, in vitro drug release curve also further confirmed that GL had a promising drug sustained-release effect. In particular, a series of in vitro tests such as cell activity, apoptosis, colony formation, scratch, invasion, and cell cycle assays were performed. The results indicated that GL significantly enhanced the pro-apoptotic effect on A549 cells. Most cell cycles of A549 cells were blocked in the G0/G1 phase influenced by GL, thus inhibiting the proliferation of cancer cells. In vivo anti-tumor studies showed that compared with pure GEB, GL had a significant inhibiting effect on NSCLC. In conclusion, the GL which was synthesized by a simple method in this study significantly improved the treatment effect of cancer cells, which proved that the nanoliposome carrier had an excellent application prospect in the treatment of lung cancer.

CHRONIC ECZEMA MANAGED WITH AYURVEDIC TREATMENT - A CASE STUDY

Background: Atopic dermatitis, also known as atopic eczema, is a chronic inflammatory skin condition characterized by pruritic, erythematous, and scaly skin lesions often localized to the flexural surfaces of the body. A genetic defect in the filaggrin protein is thought to cause atopic dermatitis by disrupting the ep-idermis. This disruption, in turn, results in contact between immune cells in the dermis and antigens from the external environment leading to intense itching, scratching, and inflammation. Scratching can then lead to further disruption and inflammation of the epidermal skin barrier; this has been described as the itch scratch cycle. According to Ayurveda, it is Raktapradoshajavikara, in which Tridosha are involved, with dominance of Kapha. The management available in current mainstream medicine is unsatisfactory; Various Ayurvedic treatments have been in use for these manifestations. Case Presentation: A 55 years old female patient presented with complaints of itching in both legs, some-times in elbows, patches in both legs since 4 years. She has also known case of HTN since 10 years. Management &amp; Outcome: Patient was admitted in Vasant Prabha Ayurvedic Hospital and was put on Ayurvedic treatment that consisted of whole body Abhyanga, Bashpaswedana, rectal drug administration (Niruhbasti) and other medicaments. She stayed for 30 days in the hospital. This case highlights the im-portance of Ayurvedic treatment in providing fast improvement in skin disease. What benefits the lady could not get in last four years have been achieved by her in just 30 days.

Fictive Scratching Patterns in Brain Cortex-Ablated, Midcollicular Decerebrate, and Spinal Cats.

Background: The spinal cord’s central pattern generators (CPGs) have been explained by the symmetrical half-center hypothesis, the bursts generator, computational models, and more recently by connectome circuits. Asymmetrical models, at odds with the half-center paradigm, are composed of extensor and flexor CPG modules. Other models include not only flexor and extensor motoneurons but also motoneuron pools controlling biarticular muscles. It is unknown whether a preferred model can explain some particularities that fictive scratching (FS) in the cat presents. The first aim of this study was to investigate FS patterns considering the aiming and the rhythmic periods, and second, to examine the effects of serotonin (5HT) on and segmental inputs to FS.Methods: The experiments were carried out first in brain cortex-ablated cats (BCAC), then spinalized (SC), and for the midcollicular (MCC) preparation. Subjects were immobilized and the peripheral nerves were used to elicit the Monosynaptic reflex (MR), to modify the scratching patterns and for electroneurogram recordings.Results: In BCAC, FS was produced by pinna stimulation and, in some cases, by serotonin. The scratching aiming phase (AP) initiates with the activation of either flexor or extensor motoneurons. Serotonin application during the AP produced simultaneous extensor and flexor bursts. Furthermore, WAY 100635 (5HT1A antagonist) produced a brief burst in the tibialis anterior (TA) nerve, followed by a reduction in its electroneurogram (ENG), while the soleus ENG remained silent. In SC, rhythmic phase (RP) activity was recorded in the soleus motoneurons. Serotonin or WAY produced FS bouts. The electrical stimulation of Ia afferent fibers produced heteronymous MRes waxing and waning during the scratch cycle. In MCC, FS began with flexor activity. Electrical stimulation of either deep peroneus (DP) or superficial peroneus (SP) nerves increased the duration of the TA electroneurogram. Medial gastrocnemius (MG) stretching or MG nerve electrical stimulation produced a reduction in the TA electroneurogram and an initial MG extensor burst. MRes waxed and waned during the scratch cycle.Conclusion: Descending pathways and segmental afferent fibers, as well as 5-HT and WAY, can change the FS pattern. To our understanding, the half-center hypothesis is the most suitable for explaining the AP in MCC.

Breaking the Itch–Scratch Cycle: Topical Options for the Management of Chronic Cutaneous Itch in Atopic Dermatitis

Chronic itch is an unpleasant sensation that triggers a desire to scratch that lasts for six weeks or more. It is a major diagnostic symptom of myriad diseases, including atopic dermatitis for which it is the most prominent feature. Chronic itch can be hugely debilitating for the sufferer, damaging in terms of both the monetary cost of treatment and its socioeconomic effects, and few treatment options exist that can adequately control it. Corticosteroids remain the first line treatment strategy for atopic dermatitis, but due to the risks associated with long-term use of corticosteroids, and the drawbacks of other topical options such as topical calcineurin inhibitors and capsaicin, topical options for itch management that are efficacious and can be used indefinitely are needed. In this review, we detail the pathophysiology of chronic pruritus, its key features, and the disease most commonly associated with it. We also assess the role of the skin and its components in maintaining a healthy barrier function, thus reducing dryness and the itch sensation. Lastly, we briefly detail examples of topical options for the management of chronic pruritus that can be used indefinitely, overcoming the risk associated with long-term use of corticosteroids.

Scratching Counteracts IL-13 Signaling by Upregulating the Decoy Receptor IL-13Rα2 in Keratinocytes.

The vicious itch–scratch cycle is a cardinal feature of atopic dermatitis (AD), in which IL-13 signaling plays a dominant role. Keratinocytes express two receptors: The heterodimeric IL-4Rα/IL-13Rα1 and IL-13Rα2. The former one transduces a functional IL-13 signal, whereas the latter IL-13Rα2 works as a nonfunctional decoy receptor. To examine whether scratch injury affects the expression of IL-4Rα, IL-13Rα1, and IL-13Rα2, we scratched confluent keratinocyte sheets and examined the expression of three IL-13 receptors using quantitative real-time PCR (qRT-PCR) and immunofluorescence techniques. Scratch injuries significantly upregulated the expression of IL13RA2 in a scratch line number-dependent manner. Scratch-induced IL13RA2 upregulation was synergistically enhanced in the simultaneous presence of IL-13. In contrast, scratch injuries did not alter the expression of IL4R and IL13RA1, even in the presence of IL-13. Scratch-induced IL13RA2 expression was dependent on ERK1/2 and p38 MAPK signals. The expression of IL-13Rα2 protein was indeed augmented in the scratch edge area and was also overexpressed in lichenified lesional AD skin. IL-13 inhibited the expression of involucrin, an important epidermal terminal differentiation molecule. IL-13-mediated downregulation of involucrin was attenuated in IL-13Rα2-overexpressed keratinocytes, confirming the decoy function of IL-13Rα2. Our findings indicate that scratching upregulates the expression of the IL-13 decoy receptor IL-13Rα2 and counteracts IL-13 signaling.

Comment on van Casteren et al. (2018): softer metallic spheres do abrade harder enamel.

Comment on van Casteren et al. (2018): softer metallic spheres do abrade harder enamel.

Itch and psyche: psychiatric aspects of pruritus.

Itch, also referred to as pruritus, is an unpleasant cutaneous sensation provoking the desire to scratch. It is often an uncomfortable, subjective sensation responsible for decreased quality of life in a variety of psychodermatological conditions. Comorbid psychiatric conditions, including depression and anxiety, are frequently associated with itch and scratch cycle. The reciprocal and intricate relationship between the psyche and itch has been widely studied. The neurobiology of itch involves the complexity of specific mediators, itch-related neuronal pathways, and central processing of itch. The connection between itch and the psyche can be grouped under three headings: pruritic diseases with psychosocial sequelae, pruritic diseases aggravated by psychosocial factors, and psychiatric disorders causing pruritus. Itch and pain modulation go together in most circumstances and involve various substances including histamine, interleukins, protease-activated receptors, transient receptor potential receptors, opioids, and cannabinoids. The close interaction between keratinocytes and nerve endings modulating pain and itch also play a major role. Management of itch associated with its psychosomatic components is directed at an underlying cause and adopting a holistic approach to address not only dermatologic and somatosensory aspects, but also the cognitive, emotional, and psychosocial components. An integrated multidisciplinary team consisting of a dermatologist, psychiatrist, psychologist, and social worker is vital in addressing the multifaceted aspects of pruritus.

Hind limb motoneurons activity during fictive locomotion or scratching induced by pinna stimulation, serotonin, or glutamic acid in brain cortex-ablated cats

In brain cortex‐ablated cats (BCAC), hind limb motoneurons activity patterns were studied during fictive locomotion (FL) or fictive scratching (FS) induced by pinna stimulation. In order to study motoneurons excitability: heteronymous monosynaptic reflex (HeMR), intracellular recording, and individual Ia afferent fiber antidromic activity (AA) were analyzed. The intraspinal cord microinjections of serotonin or glutamic acid effects were made to study their influence in FL or FS. During FS, HeMR amplitude in extensor and bifunctional motoneurons increased prior to or during the respective electroneurogram (ENG). In soleus (SOL) motoneurons were reduced during the scratch cycle (SC). AA in medial gastrocnemius (MG) Ia afferent individual fibers of L6‐L7 dorsal roots did not occur during FS. Flexor digitorum longus (FDL) and MG motoneurons fired with doublets during the FS bursting activity, motoneuron membrane potential from some posterior biceps (PB) motoneurons exhibits a depolarization in relation to the PB (ENG). It changed to a locomotor drive potential in relation to one of the double ENG, PB bursts. In FDL and semitendinosus (ST) motoneurons, the membrane potential was depolarized during FS, but it did not change during FL. Glutamic acid injected in the L3‐L4 spinal cord segment favored the transition from FS to FL. During FL, glutamic acid produces a duration increase of extensors ENGs. Serotonin increases the ENG amplitude in extensor motoneurons, as well as the duration of scratching episodes. It did not change the SC duration. Segregation and motoneurons excitability could be regulated by the rhythmic generator and the pattern generator of the central pattern generator.

Tribological evaluation of soft metallic multilayer coatings for wear applications based on a multiple pass scratch test method

The multiple pass scratch test method was employed for characterising the tribological performance of soft metallic multilayer coatings under the linear sliding wear situation. For this purpose, three different structures of tin (Sn) based coating (<15Hv0.03) were produced by electroplating process on relatively hard metallic substrates (117Hv0.1). The coating structures studied include a benchmark monolayer coating with soft Sn matrix, and two multilayer coatings with 3-layers and 5-layers of soft Sn matrix and hard SnNi intermetallic sublayer (s). The test method involves sliding a 100Cr6 steel ball against the Sn coated surface under loaded condition for a certain length and then repeating the process 50 times in a unidirectional cyclic manner. Various loading conditions were applied to identify the correct load in order to eliminate the influence of surface roughness of coating and hardness of substrate on the tribological results. Finally, load of 10 N allowed the ball probe to remove a small amount of the coating material in each scratch cycle and differentiate between the characteristic friction and wear behaviour of different coating structures layer-by-layer. Post-test surface and cross-section of worn coating regions were analysed, and the scratch and Vickers hardness of fresh coating surfaces were measured, to correlate the tribological behaviour with the respective coating structure. Results clearly showed the beneficial effects of the lubricious intermetallic sublayer within 3-layers and 5-layers Sn coating structures. The improvement in performance was even higher with lesser thickness of sublayers in 5-layers structure. Apparently, the hard intermetallic sublayer strengths the multilayer structure and at the same time enhances its wear resistance due to increase in the overall hardness of coating. Therefore, the multiple pass scratch test method successfully compared the tribological performance of soft Sn based coatings under the carefully selected test conditions.

Psychological Interventions in the Treatment of Chronic Itch.

Patients with chronic itch suffer from higher levels of depression and anxiety than their healthy counterparts. Furthermore, psychological factors, such as stress, are known to aggravate itch. The mere act of thinking about itching can induce the sensation. Interventions like habit reversal training and arousal reduction have been shown to have positive effects on itch relief. Yet, there is still limited data on the psychological management to control the itch scratch cycle and a description of methods suitable to address itch. In this review, we describe different psychological interventions shown to be effective in the treatment of chronic itch. We also provide suggestions based on our experience of suitable interventions for patients with different types of itch.

Cytokines as therapeutic targets in skin inflammation

This review focuses on treatment targets for the most common inflammatory skin diseases, eczema and psoriasis with an emphasis on cytokines expressed in the uppermost layer of the skin which is easily accessible for diagnostic and therapeutic approaches. Recently, a significant body of research has highlighted the influence of the skin barrier and the patients’ microbiome on skin inflammatory responses and we will comment on their impact on mediator regulation. Itch is a prominent dermatology symptom which is influenced by cytokines and can via itch–scratch cycle impact on the skin barrier and mediator expression associated with damage. Taking the contribution of pruritus and superficial skin damage into account, we address cytokines as targets for stratified treatment approaches in subgroups of eczema and psoriasis.

Pruritus in older people

SummaryPruritus in older people is caused by a wide range of dermatological, systemic, neurological and psychogenic diseases. It can also be attributed to various cutaneous drug reactions. The dermatological, neurological and immunological changes associated with ageing predispose older people to pruritus of a wide range of aetiologies. The most common cause of pruritus in older people is xerosis, or dry skin. Regular use of emollients is the mainstay of treatment for pruritus of any cause, with general measures aiming to ensure optimal skin hydration and to prevent the itch–scratch cycle. Topical treatments are generally better tolerated for localized pruritus. Anti-histamines are the predominant agents to treat pruritus, but can be inadequate in many cases. Numerous other systemic agents have been demonstrated to alleviate pruritus depending on the cause, but may be limited by their adverse effects. This article reviews the current published literature on pruritus in older people, with a practical approach to its evaluation and management in non-specialist settings.

Rhythmic activity of feline dorsal and ventral spinocerebellar tract neurons during fictive motor actions

Neurons of the dorsal spinocerebellar tracts (DSCT) have been described to be rhythmically active during walking on a treadmill in decerebrate cats, but this activity ceased following deafferentation of the hindlimb. This observation supported the hypothesis that DSCT neurons primarily relay the activity of hindlimb afferents during locomotion, but lack input from the spinal central pattern generator. The ventral spinocerebellar tract (VSCT) neurons, on the other hand, were found to be active during actual locomotion (on a treadmill) even after deafferentation, as well as during fictive locomotion (without phasic afferent feedback). In this study, we compared the activity of DSCT and VSCT neurons during fictive rhythmic motor behaviors. We used decerebrate cat preparations in which fictive motor tasks can be evoked while the animal is paralyzed and there is no rhythmic sensory input from hindlimb nerves. Spinocerebellar tract cells with cell bodies located in the lumbar segments were identified by electrophysiological techniques and examined by extra- and intracellular microelectrode recordings. During fictive locomotion, 57/81 DSCT and 30/30 VSCT neurons showed phasic, cycle-related activity. During fictive scratch, 19/29 DSCT neurons showed activity related to the scratch cycle. We provide evidence for the first time that locomotor and scratch drive potentials are present not only in VSCT, but also in the majority of DSCT neurons. These results demonstrate that both spinocerebellar tracts receive input from the central pattern generator circuitry, often sufficient to elicit firing in the absence of sensory input.

Nalfurafine hydrochloride for the treatment of pruritus

Introduction: Severe pruritus associated with end-stage renal disease is a particularly troublesome complication, because no effective treatment has been established. However, based on the findings of a recent randomized controlled trial, nalfurafine hydrochloride was officially approved in Japan for the treatment of resistant pruritus in hemodialysis patients.Areas covered: This review is based upon a PubMed search and personal experience with nalfurafine hydrochloride. The pharmacokinetics and pharmacodynamics of nalfurafine hydrochloride are reviewed and its efficiency and potential adverse effects are discussed, mainly based on the findings of randomized controlled trials.Expert opinion: A recent long-term open trial showed that the effect of nalfurafine hydrochloride was enhanced by continuous, long-term administration. It will be of future interest to investigate its effect on excoriations, lichen simplex, prurigo nodularis and acquired perforating dermatosis (all caused by uremic pruritus), because it targets both the skin and the central nervous system. In clinical practice, it should be kept in mind that basic skin care with emollients and other topical drugs is essential for stopping the itch–scratch cycle, and the resultant skin barrier dysfunction.