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Multiple Chemical Sensitivity (MCS) is a chronic condition characterized by reports of recurrent symptoms in response to low level exposure to various chemical substances. Recent findings suggests that dysregulation of the immune system may play a role in MCS pathophysiology. The aim of this study was to examine baseline and low dose n-butanol-induced upper airway inflammatory response profiles in MCS subjects versus healthy controls. Eighteen participants with MCS and 18 age- and sex-matched healthy controls were enrolled in the study. Epithelial lining fluid was collected from the nasal cavity at three time points: baseline, within 15 minutes after being exposed to 3.7 ppm n-butanol in an exposure chamber and four hours after exposure termination. A total of 19 cytokines and chemokines were quantified. Furthermore, at baseline and during the exposure session, participants rated the perceived intensity, valence and levels of symptoms and autonomic recordings were obtained. The physiological and psychophysical measurements during the n-butanol exposure session verified a specific response in MCS individuals only. However, MCS subjects and healthy controls displayed similar upper airway inflammatory mediator profiles (P>0.05) at baseline. Likewise, direct comparison of mediator levels in the MCS group and controls after n-butanol exposure revealed no significant group differences. We demonstrate no abnormal upper airway inflammatory mediator levels in MCS subjects before or after a symptom-eliciting exposure to low dose n-butanol, implying that upper airways of MCS subjects are functionally intact at the level of cytokine and chemokine production and secretory capacity. This suggests that previous findings of increased cytokine plasma levels in MCS are unlikely to be caused by systemic priming via excessive upper airway inflammatory processes.

ObjectivesTo investigate the pathophysiological pathways leading to symptoms elicitation in multiple chemical sensitivity (MCS) by comparing gene expression in MCS participants and healthy controls before and after a chemical exposure optimised to cause symptoms among MCS participants.The first hypothesis was that unexposed and symptom-free MCS participants have similar gene expression patterns to controls and a second hypothesis that MCS participants can be separated from controls based on differential gene expression upon a controlled n-butanol exposure.DesignParticipants were exposed to 3.7 ppm n-butanol while seated in a windowed exposure chamber for 60 min. A total of 26 genes involved in biochemical pathways found in the literature have been proposed to play a role in the pathogenesis of MCS and other functional somatic syndromes were selected. Expression levels were compared between MCS and controls before, within 15 min after being exposed to and 4 hours after the exposure.SettingsParticipants suffering from MCS and healthy controls were recruited through advertisement at public places and in a local newspaper.Participants36 participants who considered themselves sensitive were prescreened for eligibility. 18 sensitive persons fulfilling the criteria for MCS were enrolled together with 18 healthy controls.Outcome measures17 genes showed sufficient transcriptional level for analysis. Group comparisons were conducted for each gene at the 3 times points and for the computed area under the curve (AUC) expression levels.ResultsMCS participants and controls displayed similar gene expression levels both at baseline and after the exposure and the computed AUC values were likewise comparable between the 2 groups. The intragroup variation in expression levels among MCS participants was noticeably greater than the controls.ConclusionsMCS participants and controls have similar gene expression levels at baseline and it was not possible to separate MCS participants from controls based on gene expression measured after the exposure.

In this study, we investigated the time course effect of sensory eye irritation in 16 subjects exposed (i.e., eye only) to n-butanol and 1-octene. Half the subjects were exposed to n-butanol, and the remaining subjects were exposed to 1-octene. Each subject was studied on 5 different days; during each day each subject was exposed in three runs (i.e., run 1, run 2, and run 3) to a constant concentration of either n-butanol or 1-octene. We performed run 1 and run 3, both of which lasted 15 min each, to evaluate persistence in \"sensitization.\" We performed run 2, which lasted 60 min, to study the time course of sensory irritation. Ratings of ocular irritation intensity were obtained continuously during all three runs. The exposure concentrations for n-butanol were 0 mg/m 3 , 300 mg/m 3 , 900 mg/m 3 , and 3 000 mg/m 3 , and the exposure concentrations for 1-octene were 0 mg/m 3 , 6 000 mg/m 3 , 10 400 mg/m 3 , and 18 000 mg/m 3 . During run 2, we observed a slight increase in perceived eye irritation intensity for the lower concentrations of 1-octene and for all exposure concentrations of n-butanol. However, the threshold for irritation was clearly exceeded for only the 1-octene 10 400-mg/m 3 and 18 000-mg/m 3 exposures. During these two exposures, the response increased 10-fold following 20-40 min of exposure during run 2, after which the response remained constant. We investigated the existence of persistence in \"sensitization\" by comparing intensity of responses between run 1 and run 3. Persistence in \"sensitization\" was apparent for only the 1-octene exposure.

Multidimensional food perception is based mainly on gustatory and olfactory function. Recent research has demonstrated that hypobaric pressure impairs gustatory function and that background noise or distracting auditory stimulation impairs olfactory function. Using a hypobaric chamber, the odor identification, discrimination, and thresholds as well as taste identification and threshold scores were measured in 16 healthy male volunteers under normal and hypobaric (6380 ft) conditions using clinically validated tests. In both conditions, background noise was either canceled out or replaced by white noise presentation (70 dB sound pressure level). Olfactory sensitivity for n-butanol and gustatory sensitivity were impaired in a hypobaric atmosphere. White noise did not influence the odor test results. White noise stimulation impaired sensitivity for sour and sweet but not for bitter or salty tastants. We conclude that hypobaric or noisy environments could impair gustatory and olfactory sensitivity selectively for particular tastants and odorants.

Background Glucocorticoid-induced osteoporosis (GIOP) represents the predominant type of secondary bone loss disorder, linked to a substantially elevated incidence of pathological fractures in clinical populations. Modified Yanghe Decoction (MYHD), a classical Chinese medicinal formula, has demonstrated therapeutic potential in managing osteoporotic conditions. Nevertheless, the specific mechanisms underlying MYHD’s effectiveness against GIOP require further elucidation, posing challenges for broader clinical implementation. Methods We performed comprehensive analysis of bioactive constituents in the MYHD n-butanol (MYHD-NB) fraction through high-performance liquid chromatography, followed by mechanistic exploration of its biological effects across experimental models. Ten-week-old male C57BL/6J mice received dexamethasone (DEX)-induced modeling and were administered either MYHD or varying concentrations of MYHD-NB via oral gavage. Following an 8-week intervention, femoral specimens underwent multimodal evaluation including histopathological examination, micro-computed tomography imaging, and advanced molecular detection techniques (immunohistochemistry/immunofluorescence). Parallel bioinformatics analysis was executed on RNA-seq datasets from osteoporotic fracture patients in the GEO repository. For in vitro experimentation, DEX-treated murine BMSCs were employed to assess MYHD-NB’s regulatory effects on cellular proliferation, migratory capacity, osteogenic differentiation potential, and ferroptotic processes. Complementary network pharmacology approaches were utilized to predict potential molecular targets and pathway interactions. Results MYHD-NB significantly improved the osteoporosis-like phenotype in mice, as indicated by the improvement of bone microstructure and the upregulation of ALP and RUNX2 expression. RNA-seq analysis of the GEO dataset showed that ferroptosis-related genes are significantly upregulated in the femurs of GIOP patients. Both in vivo and in vitro studies confirmed MYHD-NB’s capacity to mitigate dexamethasone-induced ferroptosis in BMSCs while enhancing BMSCs proliferation capacity, migratory potential, and differentiation into osteogenic lineages. Network pharmacology predictions identified HIF-1α as the pivotal regulator mediating MYHD-NB’s anti-ferroptotic effects. Molecular investigations revealed MYHD-NB’s activation of the HIF-1α/GPX4 signaling pathway, with genetic ablation of HIF-1α completely negating the compound’s therapeutic efficacy. Conclusion MYHD-NB mitigates ferroptosis triggered by DEX in BMSCs while enhancing osteogenic differentiation via the HIF-1α/GPX4 signaling pathway, elucidating its therapeutic mechanism against GIOP. These results demonstrate MYHD-NB’s superior osteogenic potential within the MYHD formulation, positioning it as a promising candidate for alternative GIOP management strategies.

Scrophularia tenuipes is an Algerian-Tunisian endemic species, which has not been studied yet. Ethyl acetate (EA) and n-butanol (Bu) fractions obtained from Scrophularia tenuipes were investigated for their health benefit properties, in particular with respect to in vivo/in vitro anti-inflammatory and antioxidant activities, as well as their potential to inhibit key enzymes with impact in diabetes (α-glucosidase and α-amylase). The fractions had a distinct phytochemical composition, of which EA was richer in total phenolic compounds (225 mg GAE/g) and mostly composed of the phenylethanoid acetyl martynoside. Compared to EA, Bu had higher amounts of total flavonoids, and according to the result obtained from UHPLC-DAD-ESI-MSn analysis, harpagoside (iridoid) was its major phytochemical. EA fraction was quite promising with regard to the in vivo (at 200 mg/kg, po) anti-inflammatory effect (62% and 52% for carrageenan-induced rat paw edema and xylene-induced ear edema tests, respectively), while Bu fraction exhibited a stronger antioxidant capacity in all tests (IC50 = 68 µg/mL, IC50 = 18 µg/mL, IC50 = 18 µg/mL and A0.50 = 43 µg/mL for DPPH●, ABTS•+, O2•− scavenging assays and cupric-reducing antioxidant capacity method, respectively). Both fractions also showed a strong effect against α-amylase enzyme (IC50 = 8 µg/mL and 10 µg/mL for EA and Bu fraction, respectively).

Purpose Multiple chemical sensitivity (MCS) is a prevalent medically unexplained symptom characterized by symptom reactions to everyday chemical exposure below hygienic thresholds. The aim of this study was to investigate the expressions of hyper-reactivity in MCS during whole-body exposure to low concentrations of the odorant n -butanol. Methods We exposed 18 participants with MCS and 18 non-ill controls to a low concentration of the odorant n -butanol using an exposure chamber. The first 10 min constituted blank exposure, after which the n -butanol concentration increased and reached a plateau at 11.5 mg/m 3 . Results MCS participants, compared with controls, reported greater perceived odor intensities, more unpleasantness to the exposure and increasing symptoms over time. MCS participants also expressed higher pulse rate and lower pulse rate variability than controls did. No group differences were found for breathing rate or tonic electrodermal activity responses. Conclusions We conclude that MCS sufferers differ from healthy controls in terms of autonomic responses, symptoms and chemosensory perception during chemical exposure.

Background Periploca aphylla is used by local population and indigenous medicine practitioners as stomachic, tonic, antitumor, antiulcer, and for treatment of inflammatory disorders. The aim of this study was to evaluate antidiabetic effect of the extract of P. aphylla and to investigate antioxidant and hypolipidemic activity in streptozotocin (STZ)-induced diabetic rats. Methods The present research was conducted to evaluate the antihyperglycemic potential of methanol extract of P. aphylla (PAM) and subfractions n-hexane (PAH), chloroform (PAC), ethyl acetate (PAE), n-butanol (PAB), and aqueous (PAA) in glucose-overloaded hyperglycemic Sprague-Dawley rats. Based on the efficacy, PAB (200 mg/kg and 400 mg/kg) was tested for its antidiabetic activity in STZ-induced diabetic rats. Diabetes was induced via intraperitoneal injection of STZ (55 mg/kg) in rat. Blood glucose values were taken weekly. HPLC-DAD analysis of PAB was carried out for the presence of various polyphenols. Results HPLC-DAD analysis of PAB recorded the presence of rutin, catechin, caffeic acid, and myricetin. Oral administration of PAB at doses of 200 and 400 mg/kg for 21 days significantly restored (P < 0.01) body weight (%) and relative liver and relative kidney weight of diabetic rats. Diabetic control rats showed significant elevation (P < 0.01) of AST, ALT, ALP, LDH, total cholesterol, triglycerides, LDL, creatinine, total bilirubin, and BUN while reduced (P < 0.01) level of glucose, total protein, albumin, insulin, and HDL in serum. Count of blood cells and hematological parameters were altered in diabetic rats. Further, glutathione peroxidase, catalase, superoxide dismutase, glutathione reductase, and total soluble protein concentration decreased while concentration of thiobarbituric acid reactive substances and percent DNA damages increased (P < 0.01) in liver and renal tissues of diabetic rats. Histopathological damage scores increased in liver and kidney tissues of diabetic rats. Intake of PAB (400 mg/kg) resulted in significant improvement (P < 0.01) of above parameters, and results were comparable to that of standard drug glibenclamide. Conclusion The result suggests the antihyperglycemic, antioxidant, and anti-inflammatory activities of PAB treatment in STZ-compelled diabetic rat. PAB might be used as new therapeutic agent in diabetic patients to manage diabetes and decrease the complications.

Objective: To review the literature on carcinogen derived biomarkers of exposure to secondhand tobacco smoke (SHS). These biomarkers are specifically related to known carcinogens in tobacco smoke and include urinary metabolites, DNA adducts, and blood protein adducts. Method: Published reviews and the current literature were searched for relevant articles. Results: The most consistently elevated biomarker in people exposed to SHS was 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) and its glucuronides (NNAL-Gluc), urinary metabolites of the tobacco specific lung carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). The tobacco specificity of this biomarker as well as its clear relation to an established lung carcinogen are particularly appropriate for its application in studies of SHS exposure. Conclusion: The results of the available carcinogen derived biomarker studies provide biochemical data which support the conclusion, based on epidemiologic investigations, that SHS causes lung cancer in non-smokers.

The ion current induced by the glutamate receptor agonist N-methyl-D-aspartate (NMDA) in voltage-clamped hippocampal neurons was inhibited by ethanol (EtOH). Inhibition increased in a concentration-dependent manner over the range 5 to 50 mM, a range that also produces intoxication. The amplitude of the NMDA-activated current was reduced 61 percent by 50 mM EtOH; in contrast, this concentration of EtOH reduced the amplitude of current activated by the glutamate receptor agonists kainate and quisqualate by only 18 and 15 percent, respectively. The potency for inhibition of the NMDA-activated current by several alcohols is linearly related to their intoxicating potency, suggesting that alcohol-induced inhibition of responses to NMDA receptor activation may contribute to the neural and cognitive impairments associated with intoxication.