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Acta Dermatovenerologica Croatica : ADC Mar 2024Acquired circumscribed hyperpigmented patches and plaques have various differential diagnoses, including post-inflammatory hyperpigmentation and mycosis fungoides (MF)....
Acquired circumscribed hyperpigmented patches and plaques have various differential diagnoses, including post-inflammatory hyperpigmentation and mycosis fungoides (MF). Leukomelanoderma is an uncommon cutaneous condition in which the pathogenesis is not fully elucidated. It has been reported that leukomelanoderma occurs after allergic contact dermatitis from hydroquinone or acute cutaneous graft-versus-host disease (1,2). Hyperpigmented MF is a cutaneous T-cell lymphoma with a frequent CD8+ phenotype (3). Herein, we report a case of leukomelanoderma clinically and histologically resembling hyperpigmented MF. A 55-year-old Japanese woman was referred to our department for evaluation of reticulate pigmentation with pruritic erythema on the face. She had used commercially available depigmenting cosmetic reagents for 20 years and ointment containing 10% hydroquinone for 3 months. Physical examination revealed diffuse hyperpigmentation and demarcated hypopigmented macules on the face and neck (Figure 1, a). Dermoscopy showed depigmented spots and reticulated plus dotted hyperpigmentation; it presented a pseudo-pigment network (Figure 1, b). Histological examination of a tissue specimen biopsied from the lesion showed superficial band-like lymphocytic infiltration in dermis accompanying single cells or small clusters in epidermis (Figure 1, c). Interface changes were observed together with melanophages in the dermis. Melan-A-positive melanocytes were absent. Immunohistochemical analysis demonstrated that the epidermotropic lymphocytes were CD3+CD7-, and they had predominance of CD8+ cells (Figure 1, d). These immunohistochemical results mimicked MF. However, PCR analysis of the T-cell receptor g-gene rearrangement was negative. Closed patch test result with hydroquinone (5% pet.) was graded D2 (+?) and D3 (+). Ten months after discontinuing cosmetic reagents and hydroquinone, the pigmentary changes showed improvement. The pathomechanism of leukomelanoderma is unclear. Although post-inflammatory pigmentation due to allergic or contact dermatitis together with direct depigmenting effects from hydroquinone use has been suggested (1), the immunophenotype of T-cells has not been examined. As observed in our patient, interface changes with melanophages, in addition to frequent CD8+ phenotype of the epidermotropism and dermal infiltrate of lymphocytes, were characteristic for hyperpigmented MF (3). Moreover, minimal CD7 expression was a specific finding for MF (4). T-cell receptor clonality was negative in our patient, but the clonality appears to be detected by PCR in up to 50% of the patients with early MF (3). In contrast, the closed patch test was positive for hydroquinone in our patient, and it is reported that CD8+ T-cells are recruited to the interphase between the epidermis and the dermis of the patients with allergic contact dermatitis (5). CD8+ T-cells might contribute to acute cutaneous graft-versus-host disease-like interface changes and destroy melanocytes in the leukomelanoderma lesion. Allergic contact dermatitis presenting as leukomelanoderma was thus suggested in our patient. However, further reports and studies are required to support this issue. Therefore, we considered it necessary to follow the patient, since MF was not absolutely eliminated.
Topics: Humans; Female; Middle Aged; Mycosis Fungoides; Hyperpigmentation; Skin Neoplasms; Diagnosis, Differential
PubMed: 38946191
DOI: No ID Found -
Contact Dermatitis Jun 2024Fragrance substances are a frequent cause of contact allergy worldwide. Fragrance exposure varies by sex, age and possibly country, influenced by cosmetic availability,...
BACKGROUND
Fragrance substances are a frequent cause of contact allergy worldwide. Fragrance exposure varies by sex, age and possibly country, influenced by cosmetic availability, environmental conditions and cultural practices.
OBJECTIVES
To systematically review and gather prevalence of sensitization to fragrance mix I (FM I) and fragrance mix II (FM II) in consecutively patch-tested European dermatitis patients.
METHOD
A total of 4134 publications on patch test results of European dermatitis patients, published from 1981 to 2022, were systematically reviewed according to a previously registered and published PROSPERO protocol.
RESULTS
Eighty-four eligible original articles were analysed. Overall prevalence of sensitization to fragrance mix I (FM I) was 6.81% (95% CI: 6.37-7.28), and FM II was 3.64% (95% CI: 3.3-4.01). Sensitization to FM I was most prevalent in Central and Eastern Europe and to FM II in Western Europe. No clear time trends were observed. Among paediatric dermatitis patients, sensitization prevalence for FM I and FM II was 4.09% (95% CI: 3.37-4.96) and 2.17% (95% CI: 1.53-3.07).
CONCLUSION
The frequency of positive patch test results for both FMI and FMII remains high. Sensitization is also prevalent among children. Enhanced regulation and labelling of cosmetic products play a vital role in averting exposure and sensitization to fragrance allergens.
PubMed: 38945918
DOI: 10.1111/cod.14618 -
American Journal of Botany Jun 2024Theory predicts and empirical studies have shown that ecologically manipulated communities with high species diversity are resistant to invasion, but do these...
PREMISE
Theory predicts and empirical studies have shown that ecologically manipulated communities with high species diversity are resistant to invasion, but do these predictions and results hold true when applied to highly competitive invaders in natural communities? Few studies of diversity-mediated invasion resistance have measured both invasion resistance and invader impact in the same study.
METHODS
We used a two-year field experiment to test: (1) diversity-mediated competitive resistance to patch expansion by the grass, Microstegium vimineum; and (2) the competitive effect of M. vimineum on resident plant diversity. We examined responses of M. vimineum to two native plant density-reduction treatments that had opposite effects on species diversity: (1) reducing species richness via the removal of rare species; and (2) reducing dominance by reducing the density of the dominant resident species. We examined the effects of M. vimineum reduction by pre-emergent herbicide on resident diversity in the second year of the study.
RESULTS
Neither rare species removal nor dominant species reduction significantly increased M. vimineum density (relative growth rate). The pre-emergent herbicide dramatically reduced M. vimineum in year 2 of the study, but not most resident plants, which were perennials and indirectly benefited from the herbicide at a more productive site, presumably due to reduced competition from M. vimineum.
CONCLUSIONS
Diversity-mediated resistance did not effectively deter invasion by a highly competitive invader. In the case of M. vimineum and at more productive sites, it would appear that nearly complete removal of this invader is necessary to preserve plant species diversity.
PubMed: 38943238
DOI: 10.1002/ajb2.16362 -
European Journal of Pharmacology Jun 2024Nicotine has been shown to enhance object recognition memory in the novel object recognition (NOR) test by activating excitatory neurons in the medial prefrontal cortex...
Nicotine has been shown to enhance object recognition memory in the novel object recognition (NOR) test by activating excitatory neurons in the medial prefrontal cortex (mPFC). However, the exact neuronal mechanisms underlying the nicotine-induced activation of mPFC neurons and the resultant memory enhancement remain poorly understood. To address this issue, we performed brain-slice electrophysiology and the NOR test in male C57BL/6J mice. Whole-cell patch-clamp recordings from layer V pyramidal neurons in the mPFC revealed that nicotine augments the summation of evoked excitatory postsynaptic potentials (eEPSPs) and that this effect was suppressed by N-[3,5-Bis(trifluoromethyl)phenyl]-N'-[2,4-dibromo-6-(2H-tetrazol-5-yl)phenyl]urea (NS5806), a voltage-dependent potassium (Kv) 4.3 channel activator. In line with these findings, intra-mPFC infusion of NS5806 suppressed systemically administered nicotine-induced memory enhancement in the NOR test. Additionally, miRNA-mediated knockdown of Kv4.3 channels in mPFC pyramidal neurons enhanced object recognition memory. Furthermore, inhibition of A-type Kv channels by intra-mPFC infusion of 4-aminopyridine was found to enhance object recognition memory, while this effect was abrogated by prior intra-mPFC NS5806 infusion. These results suggest that nicotine augments the summation of eEPSPs via the inhibition of Kv4.3 channels in mPFC layer V pyramidal neurons, resulting in the enhancement of object recognition memory.
PubMed: 38942263
DOI: 10.1016/j.ejphar.2024.176790 -
Current Biology : CB Jun 2024Animal foraging is fundamentally shaped by food distribution and availability. However, the quantification of spatiotemporal food distribution is rare but crucial to...
Animal foraging is fundamentally shaped by food distribution and availability. However, the quantification of spatiotemporal food distribution is rare but crucial to explain variation in foraging behavior among species, populations, or individuals. Clumped but ephemeral food sources enable rapid energy intake but require increased effort to find, can generate variable foraging success, and force animals to forage more efficiently. We quantified seasonal shifts in the availability of such resources to test the proximate effects of food distribution on changes in movement patterns. The neotropical lesser bulldog bat (Noctilio albiventris) forages in a seasonal environment on emerging aquatic insects, whose numbers peak shortly after dusk. We GPS-tracked bats and quantified nocturnal insect distribution in their foraging area using floating camera traps across wet and dry seasons. Surprisingly, insects were 75% less abundant and swarms were 60% shorter lived (more ephemeral) in the wet season. As a result, wet season bats had to fly twice as far (total and maximum distance fromroost distances) and 45% longer (duration) per night. Within foraging bouts, wet season bats spent less time in each insect patch and searched longer for subsequent patches, reflecting increased temporal ephemerality and decreased spatial predictability of insects. Our results highlight the tight link between foraging effort and spatiotemporal distribution of food and the influence of constraints imposed by reproduction on behavioral flexibility and adaptations to the highly dynamic resource landscapes of mobile prey. Examining foraging behavior in light of spatiotemporal dynamics of resources can help predict how animals respond to shifts in food availability caused by escalating environmental changes.
PubMed: 38942018
DOI: 10.1016/j.cub.2024.05.074 -
Computer Methods and Programs in... Jun 2024Assessment of drug cardiotoxicity is critical in the development of new compounds and modeling of drug-binding dynamics to hERG can improve early cardiotoxicity...
BACKGROUND AND OBJECTIVE
Assessment of drug cardiotoxicity is critical in the development of new compounds and modeling of drug-binding dynamics to hERG can improve early cardiotoxicity assessment. We previously developed a methodology to generate Markovian models reproducing preferential state-dependent binding properties, trapping dynamics and the onset of I block using simple voltage clamp protocols. Here, we test this methodology with real I blockers and investigate the impact of drug dynamics on action potential prolongation.
METHODS
Experiments were performed on HEK cells stably transfected with hERG and using the Nanion SyncroPatch 384i. Three protocols, P-80, P0 and P 40, were applied to obtain the experimental data from the drugs and the Markovian models were generated using our pipeline. The corresponding static models were also generated and a modified version of the O´Hara-Rudy action potential model was used to simulate the action potential duration.
RESULTS
The experimental Hill plots and the onset of I block of ten compounds were obtained using our voltage clamp protocols and the models generated successfully mimicked these experimental data, unlike the CiPA dynamic models. Marked differences in APD prolongation were observed when drug effects were simulated using the dynamic models and the static models.
CONCLUSIONS
These new dynamic models of ten well-known I blockers constitute a validation of our methodology to model dynamic drug-hERG channel interactions and highlight the importance of state-dependent binding, trapping dynamics and the time-course of I block to assess drug effects even at the steady-state.
PubMed: 38936153
DOI: 10.1016/j.cmpb.2024.108293 -
Neural Regeneration Research Jun 2024Diabetic retinopathy is a prominent cause of blindness in adults, with early retinal ganglion cell (RGC) loss contributing to visual dysfunction or blindness. In the...
Diabetic retinopathy is a prominent cause of blindness in adults, with early retinal ganglion cell (RGC) loss contributing to visual dysfunction or blindness. In the brain, defects in y-aminobutyric acid (GABA) synaptic transmission are associated with pathophysiological and neurodegenerative disorders, whereas glucagon-like peptide-1 (GLP-1) has demonstrated neuroprotective effects. However, it is not yet clear whether diabetes causes alterations in inhibitory input to RGCs and whether and how GLP-1 protects against neurodegeneration in the diabetic retina through regulating inhibitory synaptic transmission to RGCs. In the present study, we used the patch-clamp technique to record GABA subtype A receptor-mediated miniature inhibitory postsynaptic currents (mIPSCs) in RGCs from streptozotocin-induced diabetes model rats. We found that early diabetes (4 weeks of hyperglycemia) decreased the frequency of GABAergic mIPSCs in RGCs without altering their amplitude, suggesting a reduction in the spontaneous release of GABA to RGCs. Topical administration of GLP-1 eyedrops over a period of 2 weeks effectively countered the hyperglycemia-induced downregulation of GABAergic mIPSC frequency, subsequently enhancing the survival of RGCs. Concurrently, the protective effects of GLP-1 on RGCs in diabetic rats were eliminated by topical administration of exendin-9-39, a specific GLP-1 receptor antagonist, or SR95531, a specific antagonist of the GABA subtype A receptor. Furthermore, extracellular perfusion of GLP-1 was found to elevate the frequencies of GABAergic mIPSCs in both ON- and OFF-type RGCs. This elevation was shown to be mediated by activation of the phosphatidylinositol-phospholipase C/inositol 1,4,5-trisphosphate receptor/Ca2+/protein kinase C signaling pathway downstream of GLP-1 receptor activation. Moreover, multielectrode array recordings revealed that GLP-1 functionally augmented the photoresponses of ON-type RGCs. Optomotor response tests demonstrated that diabetic rats exhibited reductions in visual acuity and contrast sensitivity that were significantly ameliorated by topical administration of GLP-1. These results suggest that GLP-1 facilitates the release of GABA onto RGCs through the activation of GLP-1 receptor, leading to the de-excitation of RGC circuits and the inhibition of excitotoxic processes associated with diabetic retinopathy. Collectively, our findings indicate that the GABA system has potential as a therapeutic target for mitigating early-stage diabetic retinopathy. Furthermore, the topical administration of GLP-1 eyedrops represents a non-invasive and effective treatment approach for managing early-stage diabetic retinopathy.
PubMed: 38934389
DOI: 10.4103/NRR.NRR-D-24-00001 -
Journal of the European Academy of... Jul 2024
Topics: Humans; Dermatitis, Allergic Contact; Female; Male; Middle Aged; Diabetes Mellitus, Type 1; Dermatitis, Irritant; Adult; Aged; Equipment and Supplies; Patch Tests
PubMed: 38924616
DOI: 10.1111/jdv.20089 -
Contact Dermatitis Jun 2024Tefillin are a religious article worn by Jewish men during daily prayer. Tefillin dermatitis secondary to potassium dichromate sensitivity is recognised, but data remain...
BACKGROUND
Tefillin are a religious article worn by Jewish men during daily prayer. Tefillin dermatitis secondary to potassium dichromate sensitivity is recognised, but data remain sparse.
OBJECTIVE
To investigate the prevalence and clinical characteristics of tefillin dermatitis.
METHODS
Patients who underwent patch testing with the European baseline series in a tertiary dermatology clinic in 2009-2023 and were diagnosed with tefillin dermatitis were identified by file review and their clinical data recorded.
RESULTS
Of 1679 consecutive male patients tested, 25 (1.49%) were diagnosed with tefillin dermatitis, accounting for 15.34% of all potassium-dichromate-positive patients (163/1679). Mean pre-symptomatic duration of tefillin use was 38 ± 16.9 years, and mean follow-up time, 3.1 ± 2.9 years. Patients presented with an eczematous rash on body areas in direct contact with the leather box or straps of the tefillin. An id reaction was noted in 32%, and sensitivity to other leather accessories, in 44%. Fourteen patients (56%) switched to chromate-free tefillin: symptoms resolved completely in 11 (79%) and partially in 2.
LIMITATIONS
Retrospective cohort design.
CONCLUSION
This is the largest study to date of tefillin dermatitis caused by sensitivity to potassium dichromate used in leather production. Prognosis after switching to chromate-free tefillin was good-to-excellent. Tefillin dermatitis may be more prevalent than previously thought.
PubMed: 38923529
DOI: 10.1111/cod.14627 -
BioRxiv : the Preprint Server For... Jun 2024The vestibular nerve is comprised of neuron sub-groups with diverse functions related to their intrinsic biophysical properties. This diversity is partly due to...
The vestibular nerve is comprised of neuron sub-groups with diverse functions related to their intrinsic biophysical properties. This diversity is partly due to differences in the types and numbers of low-voltage-gated potassium channels found in the neurons' membranes. Expression for some low-voltage gated ion channels like KCNQ4 is upregulated during early post-natal development; suggesting that ion channel composition and neuronal diversity may be shaped by hair cell activity. This idea is consistent with recent work showing that glutamatergic input from hair cells is necessary for the normal diversification auditory neurons. To test if biophysical diversity is similarly dependent on glutamatergic input in vestibular neurons, we examined the maturation of the vestibular epithelium and ganglion neurons in mice whose hair cell synapses lack glutamate. Despite lacking glutamatergic input, the knockout mice showed no notable balance deficits and crossed challenging balance beams with little difficulty. Immunolabeling of the vestibular epithelia showed normal development as indicated by an identifiable striolar zone with calyceal terminals labeled by molecular marker calretinin, and normal expression of KCNQ4 by the end of the second post-natal week. We found similar numbers of Type I and Type II hair cells in the knockout and wildtype animals, regardless of epithelial zone. Thus, the presumably quiescent Type II hair cells are not cleared from the epithelium. Patch-clamp recordings showed that biophysical diversity of vestibular ganglion neurons in the mice is comparable to that found in wildtype controls, with a similar range firing patterns at both immature and juvenile ages. However, our results suggest a subtle biophysical alteration to the largest ganglion cells (putative somata of central zone afferents); those in the knockout had smaller net conductance and were more excitable than those in the wild type. Thus, unlike in the auditory nerve, glutamatergic signaling is unnecessary for producing biophysical diversity in vestibular ganglion neurons. And yet, because the input signals from vestibular hair cells are complex and not solely reliant on quantal release of glutamate, whether diversity of vestibular ganglion neurons is simply hardwired or regulated by a more complex set of input signals remains to be determined.
PubMed: 38915604
DOI: 10.1101/2024.06.12.597464