Rejected

Tinnitus has similarities to chronic neuropathic pain where there are changes in the firing rate of different types of afferent neurons. We postulated that one possible cause of tinnitus is a change in the distribution of spontaneous firing rates in at least one type of afferent auditory nerve fibre in anaesthetised guinea pigs. In control animals there was a bimodal distribution of spontaneous rates, but the position of the second mode was different depending upon whether the fibres responded best to high (> 4 kHz) or low (≤4 kHz) frequency tonal stimulation. The simplest and most reliable way of inducing tinnitus in experimental animals is to administer a high dose of sodium salicylate. The distribution of the spontaneous firing rates was different when salicylate (350 mg/kg) was administered, even when the sample was matched for the distribution of characteristic frequencies in the control population. The proportion of medium spontaneous rate fibres (MSR, 1≤ spikes/s ≤20) increased while the proportion of the highest, high spontaneous firing rate fibres (HSR, > 80 spikes/s) decreased following salicylate. The median rate fell from 64.7 spikes/s (control) to 35.4 spikes/s (salicylate); a highly significant change (Kruskal-Wallis test p < 0.001). When the changes were compared with various models of statistical probability, the most accurate model was one where most HSR fibres decreased their firing rate by 32 spikes/s. Thus, we have shown a reduction in the firing rate of HSR fibres that may be related to tinnitus.

The oral IP receptor agonist selexipag is approved for the long-term treatment of pulmonary arterial hypertension (PAH). Treatment interruptions should be avoided due to the progressive nature of the disease. An intravenous (IV) formulation of selexipag was developed to provide a treatment option for short-term interruptions to oral selexipag. In this prospective, multicenter, open-label study, the safety, tolerability, and pharmacokinetics of temporarily switching between oral and IV selexipag were investigated (NCT03187678, ClinicalTrials.gov).

The success rate of inferior alveolar nerve block decreases exorbitantly in teeth with symptomatic irreversible pulpitis. The purpose of this prospective double blind randomized clinical trial was to evaluate the combined effect of oral premedication with ibuprofen and dexamethasone on the success rate of inferior alveolar nerve block in mandibular molars with symptomatic irreversible pulpits METHODS: Ninety-four adult patients actively experiencing pain and diagnosed with symptomatic irreversible pulpitis willingly participated in this study. Preoperative pain was recorded on the Heft Parker visual analog scale (VAS). Patients were randomly allocated to four different groups and received placebo (PLAg), 0.5 mg dexamethasone (DEXg), 800 mg ibuprofen (IBUg) and combination of 0.5mg dexamethasone and 800 mg ibuprofen (COMg). One hour after oral premedication, all patients received standard inferior alveolar nerve block containing 2% lignocaine with 1:200000 adrenaline. Access cavity preparation was initiated 15 minutes after administration of anesthesia. Pain scores were recorded on VAS after anesthesia, at dentin penetration to pulp chamber opening and on file placement. Success was defined as no or mild pain (0 mm-54 mm) throughout the procedure RESULTS: Chi square test was used for qualitative data comparison. One way ANOVA test and Post-hoc Boneferroni test showed statistically significant difference between COMg and the other 3 groups (P<0.001) CONCLUSIONS: Preoperative administration of combination of dexamethasone and ibuprofen improved the success rate of inferior alveolar nerve block in mandibular molars with symptomatic irreversible pulpitis.

The Mandragora genus (Solanaceae) is well known for its association with myths and has been used in herbal medicine since ancient times. This extensive literature review synthesizes the information currently available on the ethnobotany, Persian medicine (PM), traditional use, phytochemistry, pharmacology, and toxicity profile of Mandragora spp. The electronic search engines Scopus, Web of Science, PubMed, Google Scholar, and ScienceDirect were searched using keywords such as Mandragora, mandrake, phytochemistry, ethnopharmacology, Persian medicine, ethnobotany, and toxicity. Pertinent information was also extracted from books on PM, ethnomedicine, and dissertations. Mandragora species are found throughout the Mediterranean basin, Europe, Northern Africa, and the Himalayan regions. Traditionally, the species have been used to treat insomnia, dysuria, hemorrhoids, rheumatic pain, toothache, melancholia, and depression, among many others. In vitro studies have confirmed the biological properties of Mandragora spp. crude extracts, such as antioxidant, immunomodulatory, and enzyme-inhibiting effects. Various phytochemicals, such as alkaloids (e.g., atropine and scopolamine), coumarins (e.g., umbelliferone and scopoletin), withanolides (e.g., salpichrolide C), and lipid-like compounds (e.g., beta-sitosterol), have been isolated from Mandragora spp. Some of the pure compounds composing this plant are highlighted for their biologically active effects, including anticholinergic, antidepressant, antioxidant, and anti-inflammatory effects. Modern identifications of biological activities of the compounds isolated from Mandragora, especially alkaloids, support its traditional uses (e.g., for their narcotic effects). More in vivo studies are required to further understanding and most effectively utilize this genus, and extensive toxicological studies are required to validate its safety in clinical use.

Topical cycloplegic agents often are used in ophthalmology in the context of management of ocular inflammation. Preliminary searches of the literature provided little evidence to support their use in relieving pain or reducing inflammation. The goal of this study was to evaluate the current literature for any evidence regarding the effectiveness of cycloplegics for treatment of pain or inflammation in patients with anterior segment injury or inflammation through a systematic review and meta-analysis.

Epling and Játiva is a perennial mint from the Lamiaceae family, endemic to Mexico, predominantly from the state of Oaxaca. Due to its psychoactive properties, had been used for centuries by Mazatecans for divinatory, religious, and medicinal purposes. In recent years, its use for recreational purposes, especially among adolescents and young adults, has progressively increased. The main bioactive compound underlying the hallucinogenic effects, salvinorin A, is a non-nitrogenous diterpenoid with high affinity and selectivity for the k-opioid receptor. The aim of this work is to comprehensively review and discuss the toxicokinetics and toxicodynamics of and salvinorin A, highlighting their psychological, physiological, and toxic effects. Potential therapeutic applications and forensic aspects are also covered in this review. The leaves of can be chewed, drunk as an infusion, smoked, or vaporised. Absorption of salvinorin A occurs through the oral mucosa or the respiratory tract, being rapidly broken down in the gastrointestinal system to its major inactive metabolite, salvinorin B, when swallowed. Salvinorin A is rapidly distributed, with accumulation in the brain, and quickly eliminated. Its pharmacokinetic parameters parallel well with the short-lived psychoactive and physiological effects. No reports on toxicity or serious adverse outcomes were found. A variety of therapeutic applications have been proposed for which includes the treatment of chronic pain, gastrointestinal and mood disorders, neurological diseases, and treatment of drug dependence. Notwithstanding, there is still limited knowledge regarding the pharmacology and toxicology features of and salvinorin A, and this is needed due to its widespread use. Additionally, the clinical acceptance of salvinorin A has been hampered, especially due to the psychotropic side effects and misuse, turning the scientific community to the development of analogues with better pharmacological profiles.

is the largest genus of Myristicaceae in America, comprising about 60 species of medium-sized trees geographically spread from Mexico to southern Brazil. The plant species of this genus have been widely used in folk medicine for the treatment of several ailments, such as rheumatic pain, bronchial asthma, tumors in the joints, intestinal worms, halitosis, ulcers, and multiple infections, due to their pharmacological activity. This review presents an updated and comprehensive summary of species, particularly their ethnomedicinal uses, phytochemistry, and biological activity, to support the safe medicinal use of plant extracts and provide guidance for future research. The spp.'s ethnopharmacology, including in the treatment of stomach pain and gastric ulcers, as well as antimicrobial and tryponosomicidal activities, is attributable to the presence of a myriad of phytoconstituents, such as flavonoids, tannins, phenolic acids, lignans, arylalkanones, and sitosterol. Hence, such species yield potential leads or molecular scaffolds for the development of new pharmaceutical formulations, encouraging the elucidation of not-yet-understood action mechanisms and ascertaining their safety for humans.

Spontaneous splenic rupture (SSR) is a rare phenomenon where the spleen ruptures without associated trauma. SSR can lead to an intra-abdominal haemorrhage and an acute abdomen that can be life threatening.

Paroxysmal Hemicrania is a rare form of primary headache in children and adolescents, belonging to the group of trigeminal autonomic cephalalgias. Patients suffer from severe, short-lasting unilateral headaches accompanied by symptoms of the autonomic system on the same side of the head. The short duration of attacks distinguishes Paroxysmal Hemicrania from other trigeminal autonomic cephalalgias. Indomethacin is the treatment of choice, and its effectiveness provides a unique diagnostic criterion. However, the long-term outcomes in children are highly underreported. In this case-series, = 8 patients diagnosed with Paroxysmal Hemicrania were contacted via telephone 3.1 to 10.7 years after initial presentation. A standardized interview was conducted. = 6 patients were headache-free and no longer took indomethacin for 5.4 ± 3.4 years. The mean treatment period in these patients was 2.2 ± 1.9 years. Weaning attempts were undertaken after 1.7 ± 1.3 months; in = 3 patients, more than one weaning attempt was necessary. = 2 patients were still taking indomethacin (4.5 and 4.9 years, respectively). Both unsuccessfully tried to reduce the indomethacin treatment (two and six times, respectively). Adverse effects appeared in = 6 (75%) patients and led to a discontinuation of therapy in = 2 patients. Our long-term follow-up suggests that in a substantial proportion of pediatric patients, discontinuing indomethacin therapy is possible without the recurrence of Paroxysmal Hemicrania.

The incidence of ultrasound seromas has significantly increased after large hernial sac surgery. Several methods are available for preventing ultrasound seromas, but the clinical results are poor. It has also been demonstrated that hernial sac stump fenestration during laparoscopic incisional hernia repair surgery can significantly decrease the incidence of ultrasound seromas.