BACKGROUND: Photobiomodulation, also referred to as Low-Level Light Therapy (LLLT), has emerged as a promising intervention for pruritus, a prevalent and often distressing symptom.
OBJECTIVE: This study investigated the efficacy of low-level light therapy (LLLT) in alleviating pruritus, hyperknesis, and alloknesis induced by histamine and Mucuna pruriens.
METHODS: In a double-blind, randomized, sham-controlled trial with a split-body design, healthy volunteers underwent 6 minutes of LLLT and sham treatments in separate upper back quadrants. The histamine model was applied to the upper quadrants, and Mucuna pruriens to the lower quadrants. Pruritus intensity, alloknesis, hyperknesis, flare area, and skin temperature were measured pre and post treatment.
RESULTS: Seventeen individuals (eight females, nine males) participated in the study. In the histamine model, LLLT notably reduced itch intensity (difference = 13.9 (95% CI: 10.5 - 17.4), p = 0.001), alloknesis (difference = 0.80 (95% CI: 0.58-1.02), p = 0.001), and hyperknesis (difference = 0.48 (95% CI: 0.09-0.86), p = 0.01). Skin temperature changes were not significantly different between the two groups (difference = -2.0 (95% CI: -6.7-2.6), p = 0.37). For the Mucuna pruriens model, no significant differences were observed in any measures, including itch intensity (difference = 0.8 (95% CI: -2.3 - 3.8), p = 0.61) hyperknesis (difference = 0.08 (95% CI: -0.06-0.33), p = 0.16) and alloknesis (difference = 0. 0.09 (95% CI: -0.08-0.256), p = 0.27).
CONCLUSIONS: LLLT effectively reduced histamine-induced pruritus, alloknesis, and hyperknesis; however, LLLT was ineffective against Mucuna pruriens-induced pruritus. Further investigations are required to determine LLLT\'s effectiveness of LLLT in various pruritus models.

BACKGROUND: Diagnosing perioperative anaphylaxis (POA) is often challenging. Although a guideline recommends measuring tryptase rather than histamine, there is little evidence for this. We aimed to examine the diagnostic performance and appropriate timing of tryptase and histamine measurements for diagnosing anaphylaxis, and the association between Hypersensitivity Clinical Scoring Scheme (HCSS) scores and elevated biomarkers.
METHODS: We measured tryptase and histamine levels thrice: 30 min, 2 h, and at least 24 h after an anaphylactic event for patients with suspected anaphylaxis, and at the induction of general anesthesia and 30 min and 2 h after the start of surgery for control patients without a reaction. Absolute values and the magnitude and rate of change from baseline were evaluated. We determined the thresholds of tryptase and histamine levels with the best diagnostic performance and compared their performance.
RESULTS: Forty-five patients with perioperative anaphylaxis were included in this study. The control group included 30 patients with uneventful general anesthesia and 12 patients with a suspected but unconfirmed diagnosis of perioperative anaphylaxis. Comparison at the same measurement timings showed that tryptase generally had better diagnostic performance than histamine. Both showed better diagnostic performance when assessed using multiple measurements rather than a single measurement. The best diagnostic performance was seen with the percentage change in the higher tryptase value, whether measured at 30 min or 2 h after anaphylaxis onset, as compared to baseline. However, neither tryptase nor histamine levels correlated with HCSS scores.
CONCLUSIONS: Overall, tryptase showed better diagnostic performance than histamine. When multiple tryptase measurements are possible, parameters calculated using two acute phase measurements and the baseline level have better diagnostic performance.

A retrospective pilot study was carried out to investigate the prevalence of four variants of the diamine oxidase (DAO) encoding gene (AOC1) in Caucasian adults with symptoms of histamine intolerance. In a cohort of 100 patients and 100 healthy individuals, DAO-encoding gene non-synonymous Single Nucleotide Variations (SNVs) were genotyped by multiplex single-nucleotide primer extension (SNPE) and capillary electrophoresis, and serum DAO activity was analyzed with a radio-extraction assay. The study found that 79% of individuals with symptoms of histamine intolerance harbored one or more of the four SNVs associated with reduced DAO activity. No significant differences were found in the prevalence of any variant between the group of patients and healthy controls. However, when considering the status of the alleles associated with DAO deficiency, more homozygous alleles were observed in histamine-intolerant patients. Moreover, a slightly but statistically higher percentage of patients had a high genetic risk score, reflecting the cumulative effect of carrying multiple DAO deficiency-associated gene variants and a high load of risk alleles (homozygous). A relationship between serum DAO activity and the genetic load of one specific SNV was observed, with DAO activity being significantly lower in patients homozygous for rs2052129. These results potentially support that carrying multiple DAO deficiency-associated gene variants and a high load of risk alleles (homozygous) is more relevant than the mere presence of one or more SNVs. Further studies are needed to determine the predictive value of these DAO-encoding gene variants.

The green synthesis of zinc oxide nanoparticles (ZnO NPs) using plants has grown in significance in recent years. ZnO NPs were synthesized in this work via a chemical precipitation method with Jasminum sambac (JS) leaf extract serving as a capping agent. These NPs were characterized using UV-vis spectroscopy, FT-IR, XRD, SEM, TEM, TGA, and DTA. The results from UV-vis and FT-IR confirmed the band gap energies (3.37 eV and 3.50 eV) and the presence of the following functional groups: CN, OH, C=O, and NH. A spherical structure and an average grain size of 26 nm were confirmed via XRD. The size and surface morphology of the ZnO NPs were confirmed through the use of SEM analysis. According to the TEM images, the ZnO NPs had an average mean size of 26 nm and were spherical in shape. The TGA curve indicated that the weight loss starts at 100 °C, rising to 900 °C, as a result of the evaporation of water molecules. An exothermic peak was seen during the DTA analysis at 480 °C. Effective antibacterial activity was found at 7.32 ± 0.44 mm in Gram-positive bacteria (S. aureus) and at 15.54 ± 0.031 mm in Gram-negative (E. coli) bacteria against the ZnO NPs. Antispasmodic activity: the 0.3 mL/mL sample solution demonstrated significant reductions in stimulant effects induced by histamine (at a concentration of 1 µg/mL) by (78.19%), acetylcholine (at a concentration of 1 µM) by (67.57%), and nicotine (at a concentration of 2 µg/mL) by (84.35%). The antipyretic activity was identified using the specific Shodhan vidhi method, and their anti-inflammatory properties were effectively evaluated with a denaturation test. A 0.3 mL/mL sample solution demonstrated significant reductions in stimulant effects induced by histamine (at a concentration of 1 µg/mL) by 78.19%, acetylcholine (at a concentration of 1 µM) by 67.57%, and nicotine (at a concentration of 2 µg/mL) by 84.35%. These results underscore the sample solution\'s potential as an effective therapeutic agent, showcasing its notable antispasmodic activity. Among the administered doses, the 150 mg/kg sample dose exhibited the most potent antipyretic effects. The anti-inflammatory activity of the synthesized NPs showed a remarkable inhibition percentage of (97.14 ± 0.005) at higher concentrations (250 µg/mL). Furthermore, a cytotoxic effect was noted when the biologically synthesized ZnO NPs were introduced to treated cells.

Symptomatic dermographism (SD) is a common form of urticaria, which is triggered by stroking the skin. Brain involvement in its aetiology was investigated by means of magnetoencephalography (MEG) after provocation with histamine and dermography. Wheals were induced by histamine skin prick test and dermography in twelve SD patients and fourteen controls. Itch severity was scored on a Visual Analogue Scale (VAS). Relative power and functional connectivity (FC) were measured using a 306-channel whole-head MEG system at baseline and 10 min after histamine and dermography, and contrasted between groups and conditions. Furthermore, wheal diameter and itch scores after these procedures were correlated with the MEG values. SD patients had higher itch scores after histamine and dermography. No significant group-differences were observed in relative power or FC for any condition. In both groups, power decreases were mostly observed in the beta band, and power increases in the alpha bands, after provocation, with more regions involved in patients compared to controls. Increased FC was seen after histamine in patients, and after dermography in controls. In patients only, dermography and histamine wheal size correlated with the alpha2 power in the regions of interest that showed significant condition effects after these procedures. Our findings may be cautiously interpreted as aberrant itch processing, and suggest involvement of the central nervous system in the aetiology of SD.

BACKGROUND: The histamine-3 receptor (H3R) may have a role in cognitive processes through its action as a presynaptic heteroreceptor inhibiting the release of glutamate in the brain. To explore this, we examined anterior cingulate cortex (ACC) and striatum H3R availability in patients with schizophrenia and characterized their relationships with glutamate levels in corresponding brain regions.
METHODS: We employed a cross-sectional study, recruiting 12 patients with schizophrenia and 12 healthy volunteers. Participants underwent positron emission tomography using the H3R-specific radio ligand [11C]MK-8278, followed by proton magnetic resonance spectroscopy to measure glutamate levels, recorded as Glu and Glx. Based on existing literature, the ACC and striatum were selected as regions of interest.
RESULTS: We found significant inverse relationships between tracer uptake and Glu (r = -0.66, P = .02) and Glx (r = -0.62, P = .04) levels in the ACC of patients, which were absent in healthy volunteers (Glu: r = -0.19, P = .56, Glx: r = 0.10, P = .75). We also found a significant difference in striatal (F1,20 = 6.00, P = .02) and ACC (F1,19 = 4.75, P = .04) Glx levels between groups.
CONCLUSIONS: These results provide evidence of a regionally specific relationship between H3Rs and glutamate levels, which builds on existing preclinical literature. Our findings add to a growing literature indicating H3Rs may be a promising treatment target in schizophrenia, particularly for cognitive impairment, which has been associated with altered glutamate signaling.

BACKGROUND: Allergies often present challenges in managing itch and the effects of histamine. Cooling agents that act via transient receptor potential melastatin 8 (TRPM8) agonism have shown potential in itch management. However, animal studies on itch have limitations, as animals cannot communicate subjective events and their fur-coated skin differs from that of humans. Human studies offer more direct and reliable information.
OBJECTIVE: To investigate the effects of a specific TRPM8 agonist gel (cryosim-1) on itch induced by various pruritogens in human skin.
METHODS: Calcium imaging experiments determined the binding of cryosim-1 and histamine to their respective receptors. Thirty healthy volunteers underwent skin prick tests with pruritogens and a control vehicle. Itch and pain intensity were measured using a numerical rating scale (NRS) across 10 min. Participants were randomly assigned to pretreatments with vehicle or TRPM8 agonist gel. Tests were repeated at a later date, and skin moisture, transepidermal water loss and mechanical sensitivity were measured.
RESULTS: The in vitro study confirmed that histamine is not a TRPM8 agonist and cryosim-1 does not act as an agonist or antagonist on the human histamine 1 receptor. The TRPM8 agonist gel significantly reduced the itch intensity for all pruritogens compared with the vehicle-only gel. It also reduced itch NRS and the integrated itch score. Mechanical sensitivity was also reduced.
CONCLUSIONS: The specific TRPM8 agonist gel effectively suppressed human skin itch induced by various pruritogens. These versatile actions suggest that cooling agents may be promising treatments for multiple forms of itch stimuli.
Managing itching and the effects of histamine can be difficult for people with allergies. Cooling the skin or applying menthol provides some relief from itch, but the way they work is not fully understood. Cooling agents interact with a protein called TRPM8 (also known as the ‘cold and menthol receptor’) and have shown potential for the management of itch. However, much of the research has been done on animals and has limitations when compared with human studies. Antihistamine medications can help with histamine-induced itching, but they may not work for other causes of itch. This study investigated the effects of a specific TRPM8 agonist (a chemical that activates a receptor to produce a biologic response) gel called cryosim-1 on itch in human skin. To do this, we conducted tests on 30 healthy people using five different substances that cause itching. Participants rated the itch intensity and pain using a scale and we measured various aspects of their skin. The results showed that all substances caused significant itching compared to a control substance, but itchiness gradually decreased over time. Histamine and compound 48/80 also caused pain. However, when participants applied the TRPM8 activator gel before exposure, they experienced less itching and lower itch intensity versus the gel without the activator. There were no significant differences in pain between the TRPM8 activator and the gel without it. In summary, our findings showed that activating TRPM8 receptors with a specific substance effectively relieved itching caused by various irritants on human skin. This suggests its potential as a treatment for itch-related conditions. Further research is needed to understand its mechanisms better and evaluate its effectiveness in real-life situations.

The purpose of this study was to gain insight into histamine\'s role in the exercise inflammatory response and recovery from exercise. To explore this, young healthy participants (n = 12) performed 300 eccentric leg extensions under control (Placebo) versus histamine H1 and H2 receptor antagonism (Blockade) in a randomized cross-over study. Circulating leukocytes and cytokines were measured for 72 h after exercise. Circulating leukocytes were elevated at 6 and 12 h after exercise (p < 0.05) with the peak response being a 44.1 ± 11.7% increase with Blockade versus 13.7 ± 6.6% with Placebo (both p < 0.05 vs. baseline, but also p < 0.05 between Blockade and Placebo). Of the cytokines that were measured, only MCP-1 was elevated following exercise. The response at 6 h post-exercise was a 104.0 ± 72.5% increase with Blockade versus 93.1 ± 41.9% with Placebo (both p < 0.05 vs. baseline, p = 0.82 between Blockade and Placebo). The main findings of the present investigation were that taking combined histamine H1 and H2 receptor antagonists augmented the magnitude but not the duration of the increase of circulating immune cells following exercise. This suggests histamine is not only exerting a local influence within the skeletal muscle but that it may influence the systemic inflammatory patterns.

We evaluated the histamine 1 receptor antagonist ebastine as a potential treatment for patients with non-constipated irritable bowel syndrome (IBS) in a randomised, placebo-controlled phase 2 study.
Non-constipated patients with IBS fulfilling the Rome III criteria were randomly assigned to 20 mg ebastine or placebo for 12 weeks. Subjects scored global relief of symptoms (GRS) and abdominal pain intensity (API). A subject was considered a weekly responder for GRS if total or obvious relief was reported and a responder for API if the weekly average pain score was reduced by at least 30% vs baseline. The primary endpoints were the proportion of subjects who were weekly responders for at least 6 out of the 12 treatment weeks for both GRS and API (\'GRS+API\', composite endpoint) and for GRS and API separately.
202 participants (32±11 years, 68% female) were randomly allocated to receive ebastine (n=101) or placebo (n=101). Treatment with ebastine resulted in significantly more responders (12%, 12/92) for GRS+API compared with placebo (4%, 4/87, p=0.047) while the proportion of responders for GRS and API separately was higher for ebastine compared with placebo, although not statistically significant (placebo vs ebastine, GRS: 7% (6/87) vs 15% (14/91), p=0.072; API: 25% (20/85) vs 37% (34/92), p=0.081).
Our study shows that ebastine is superior to placebo and should be further evaluated as novel treatment for patients with non-constipated IBS.
The study protocol was approved by the local ethics committee of each study site (EudraCT number: 2013-001199-39; ClinicalTrials.gov identifier: NCT01908465).

BACKGROUND: Allergic rhinitis (AR) is an inflammatory, symptomatic disorder stimulated by antigen-specific immunoglobulin E inflammation in response to allergens. Current treatments include the use of corticosteroids and antihistamines to reduce inflammation by preventing histamine release. Palmitoylethanolamide (PEA) is reported to be an alternative treatment, shown to downregulate mast cell activation and increase the synthesis of endocannabinoid 2-Arachidonoylglycerol to reduce histamine and the symptoms of AR.
METHODS: A double-blind, randomised, placebo-controlled clinical trial in which 108 participants presenting with seasonal AR were supplemented with either 350 mg of PEA (Levagen+) or a placebo daily for two weeks. Symptom scores were recorded using the reflective total nasal symptom score (rTNSS) twice a day (morning and evening) for the two weeks, and blood was taken at baseline and week 2.
RESULTS: 101 participants completed the study with no baseline group differences. No significant difference was seen between groups for allergy symptoms scores (rTNSS) throughout the 14 days of treatment. A sub-group analysis of participants scoring over four (mild-to-moderate) on the total rTNSS at baseline showed that Levagen+ significantly reduced scores compared to the placebo group. Only 36 participants had full sets of blood taken due to COVID-19. The pathology results showed a significant difference in change from baseline between groups. The Levagen+ group had a significant decrease from baseline in histamine, IL-4, IL-8, IL-10, and TNF-α. The placebo group only had a reduction in IL-4.
CONCLUSIONS: The results of this study show that Levagen+ can alleviate AR symptoms, resulting in a reduction in histamine and inflammatory markers.