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The family of nuclear peroxisome proliferator-activated receptors (PPARα, PPARβ/δ, and PPARγ) is a set of ligand-activated transcription factors that regulate different functions in the body. Whereas activation of PPARα is known to reduce the levels of circulating triglycerides and regulate energy homeostasis, the activation of PPARγ brings about insulin sensitization and increases the metabolism of glucose. On the other hand, PPARβ when activated increases the metabolism of fatty acids. Further, these PPARs have been claimed to be utilized in various metabolic, neurological, and inflammatory diseases, neurodegenerative disorders, fertility or reproduction, pain, and obesity. A series of different heterocyclic scaffolds have been synthesized and evaluated for their ability to act as PPAR agonists. This review is a compilation of efforts on the part of medicinal chemists around the world to find novel compounds that may act as PPAR ligands along with patents in regards to PPAR ligands. The structure-activity relationship, as well as docking studies, have been documented to better understand the mechanistic investigations of various compounds, which will eventually aid in the design and development of new PPAR ligands. From the results of the structural activity relationship through the pharmacological and in silico evaluation the potency of heterocycles as PPAR ligands can be described in terms of their hydrogen bonding, hydrophobic interactions, and other interactions with PPAR.

: The aim of this study was to determine whether a non-contact sensor that detects complexion changes can be used to assess the psychological state of patients with chronic lower back pain (LBP). : Twenty-six patients with LBP (LBP group; mean age = 68.0 ± 13.9 years) and 18 control subjects without LBP (control group; mean age = 60.8 ± 16.1 years) were included in the study. All the subjects in the two groups wore headphones when asked LBP-related and LBP-unrelated questions. During questioning, the facial image of the subjects was captured using a video camera, and the complexion of the subjects was converted into red, green, and blue (RGB) values. RGB correlation coefficients (RGBCCs; range: 0-1) represent the difference in complexion between LBP-related and LBP-unrelated questions. A high RGBCC indicates that the brain is more activated by LBP-related questions than by LBP-unrelated questions. We also noted the scores of subjects on the Numerical Rating Scale (NRS), Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Pain Catastrophizing Scale (PCS), and Hospital Anxiety and Depression Scale (HADS). : There were no significant differences in RGBCC between the control and LBP groups (0.64 versus 0.56, = 0.08). In the LBP group, no correlation was observed between RGBCC and each examination item of NRS, JOABPEQ, and HADS. In contrast, a correlation was observed between RGBCC and the rumination subscale of PCS in the LBP group (Spearman's rank correlation coefficient = 0.40, = 0.04). : The complexion of patients with catastrophic thinking changes when the patients are asked LBP-related questions.

Rasagiline is a selective and irreversible inhibitor of monoamine oxidase type B with neuroprotective effect, indicated for the management of Parkinson's disease. The aim of this work was to evaluate the impact of seven alleles and of 120 additional variants located in other CYP enzymes (e.g., ), UGT enzymes (e.g., ) or other enzymes (e.g., ), and transporters (e.g., ) on the pharmacokinetic variability and safety of rasagiline. A total of 118 healthy volunteers enrolled in four bioequivalence clinical trials consented to participate in this pharmacogenetic study. alleles were not associated with the pharmacokinetic variability of rasagiline. Patients with rs1045642 G/A+A/A genotypes presented higher area under the curve adjusted by dose per weight (AUC/DW) than those with the G/G genotype ( = 0.012) and lower volume of distribution (V/F) and clearance (Cl/F) ( = 0.001 and = 0.012, respectively). Subjects with the rs2273697 A/A genotype presented lower t (i.e., the time to reach the maximum concentration, C) compared to those with G/G+G/A genotypes ( = 0.001). Volunteers with the *1/*5 genotype exhibited lower C/DW and higher t ( = 0.003 and = 0.018, respectively) than subjects with the *1/*1 diplotype. Only one adverse drug reaction was reported: headache. Our results suggest the genetic polymorphism of drug transporters, rather than metabolizing enzymes, conditions the pharmacokinetics of rasagiline.

: After major heart surgery, some patients report visual hallucinations that cannot be attributed to psychosis or delirium. This study aimed to investigate the hallucination incidence in patients after coronary artery bypass grafting with (on-pump) and without (off-pump) extracorporeal circulation. : A total of 184 consecutive patients listed for elective on- or off-pump coronary artery bypass grafting were prospectively enrolled into the study. Preoperative baseline investigations 24-48 h before surgery (t0) and postoperative follow-up 24-48 h (t1) and 5-6 days (t2) after surgery included cognitive testing and a clinical visual acuity test (Landolt rings). Patients reporting visual hallucinations were interviewed using a structured survey to record the type, timing, duration, and frequency of their hallucinations. All the patients received a neurological examination and cranial magnetic resonance imaging if indicated. : Of the patients in the sample, 155 patients underwent on-pump bypass surgery, and 29 patients received off-pump surgery. Of these, 25 patients in the on-pump group, but none in the off-pump group, reported transient visual hallucinations ( = 0.020), which could not be attributed to stroke, delirium, psychosis, migraine, or severely impaired vision. Significant correlations were observed for the occurrence of visual hallucinations and the amount of nicotine consumption and aortic clamp/extracorporeal circulation time. : Transient visual hallucinations occur in a noticeable proportion of patients after on-pump heart surgery. Knowledge of the phenomenon's benignity is important for patients to prevent anxiety and uncertainty and for treating physicians to avoid unnecessary medication and drug-induced delirium.

Atopic dermatitis (AD) is a highly recurrent chronic inflammatory skin disease, characterized by severe itching, immune imbalance, and skin barrier dysfunction. Damage to the skin barrier function is known to be the main cause of Th1/Th2 immune imbalance, due to the Th2-mediated immune response, and pro-inflammatory cytokines, including IL-4, IL-5, IL-13 and IL-31 and it plays an important role in further eliciting the environment of AD through stimulation. Currently, the most widely used drugs for the treatment of AD are corticosteroids, antihistamines and immunosuppressants (used by more than 60% of patients), which are reported to exhibit various side effects when taken for a long time. Therefore, interest in the physiological activity of safer plant-derived natural extracts is increasing. is traditionally used in oriental medicine for bruises, habitual pain, gastric and postpartum hemorrhage. Recent studies have reported that it exhibits antioxidant anti-inflammatory and anti-hepatotoxic activity, but the role and activity of in AD have not yet been studied. Therefore, in this study, the new physiological activity of in the AD environment was investigated, suggesting its potential as a natural therapeutic agent.

Uremic pruritus is a disturbing and refractory symptom in patients with advanced chronic kidney disease. Chinese herbal medicine has been reported to alleviate uremic pruritus. To investigate the effects of Chinese herbal medicine, we conducted a systematic review and meta-analysis on patients with uremic pruritus. We searched databases (prior to 3 May 2022) for randomized controlled trials on the effects of Chinese herbal medicine in treating uremic pruritus. Our meta-analysis included 3311 patients from 50 randomized controlled trials. In patients with uremic pruritus, adjunctive Chinese herbal medicine significantly improved overall effectiveness (risk ratio 1.29, 95% CI 1.23 to 1.35), quality of life, renal function, reduced pruritus score, and inflammatory biomarkers compared to control groups with hemodialysis alone or with anti-pruritic treatments. Chinese herbal medicine treatment showed a time-dependent tendency in improving the visual analog scale of dialysis patients. Compared to control groups, no significantly higher risk of adverse events in patients taking Chinese herbal medicine (risk ratio 0.60, 95% CI 0.22 to 1.63). Chinese herbal medicine appears to be effective and safe in complementing the treatment of patients with uremic pruritus.

Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by pruritus, dry skin and redness on the face and inside elbows or knees. Most patients with AD are children and youths, but it can also develop in adults. In the therapeutic aspect, treatment with corticosteroids for AD has several side effects, such as weight loss, atrophy and acne. In the current study, we examined the anti-inflammatory effect of leaves on HaCaT keratinocytes and 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis-like symptoms in BALB/c mice. We observed that treatment exhibited significant inhibition in the production of inflammatory mediators and proinflammatory cytokines, such as IL-1β, in LPS-induced HaCaT keratinocytes by downregulating the NLRP3 inflammasome activation. Moreover, inhibited the activation of JNK, AP-1 and p65, which resulted in the deformation of NLRP3 in LPS-stimulated HaCaT cells. In mice with DNCB-induced AD-like skin lesions, the administration of ameliorated the clinical symptoms, such as the dermatitis score, thickness of lesional ear skin and TEWL. Furthermore, could attenuate the activation of the immune system, such as reducing the spleen index, concentration of the IgE levels and expression of the NLRP3 inflammasome in ear tissues. Therefore, our results suggest that exerts anti-atopic dermatitis effects by inhibiting the NLRP3 inflammasome-mediated IL-1β.

Migraine is a prevalent and debilitating neurologic disorder. Advancements in understanding the underlying pathophysiological mechanisms are spearheading the effort to introduce disease-specific treatment options. In recent years this effort has largely focused on alteration of endogenous neuropeptide signaling, namely the peptides calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP). Human studies into the pathophysiological underpinnings of CGRP and PACAP in migraine are manifold and here we review the works investigating these neuropeptides in patients suffering from migraine in order to elucidate the background for developing new treatment options for this vastly disabling disorder.

There is an unmet need for novel therapeutic tools relieving chronic pain. Hydrogen sulfide (HS) is highly involved in pain processes; however, the development of ideal matrices for sulfide donor compounds remains a great pharmaceutical challenge. We aimed to establish a suitable transdermal therapeutic system (TTS) using the HS donor diallyl disulfide (DADS) as a model compound. After the preparation of DADS, its solubility was investigated in different liquid excipients (propylene glycol, polyethylene glycol, silicone oil) and its membrane diffusivity was assessed in silicone matrices of different compositions. Drug-releasing properties of DADS-containing patches with different silicone oil contents were determined with Franz and flow-through cells. We found a correlation between the liquid excipient content of the patch and the diffusion rate of DADS. DADS showed the best solubility in dimethyl silicone oil, and the diffusion constant was proportional to the amount of oil above the 3 m/m% threshold value. The 8-day-old patch showed a significantly lower, but better-regulated, drug release over time than the 4-day-old one. In conclusion, the silicone-based polymer matrix developed in this study is suitable for stable storage and optimal release of DADS, providing a good basis for a TTS applied in chronic pain.

Schistosomiasis is a neglected tropical disease (NTD) caused by blood flukes ( spp.). Schistosomatids affect a wide array of vertebrate hosts, including humans. In the present study, multiple species of schistosomatids were identified by isolating schistosomatid cercariae (SC) from naturally infected snails. We also described different biotic and abiotic factors influencing SC infections in snails and reported human cercarial dermatitis (HCD) for the first time in Bangladesh. A total of 22,012 snails of seven species: , . , , , , spp., and spp., were collected and examined. Among these snails, 581 (2.6%) belonging to five species: . , . , . , . , and . , were infected with SC. The rate of infection was the highest for . (11.1%), followed by . (5.3%), and was the lowest for . (0.4%). Prevalence in snails was the highest in September (16.8%), followed by October (9.5%) and November (8.8%), and was the lowest in colder months, such as January (1.8%) and February (2.1%). Infections with schistosomatids were more common in larger snails and snails collected from sunny areas. We confirmed the presence of , . , . , . , and by PCR and sequencing. Through a questionnaire survey, we detected HCD in 214 (53.5%) individuals, and the infection rate was almost equally distributed across all professions. Collectively, the present results suggest that lymnaeid snails are the main vector for spp. prevalent in Bangladesh, and schistosomatids with zoonotic potential are also prevalent.