Chemical composition and antinociceptive and anti-inflammatory activity of the essential oil of Hyptis crenata Pohl ex Benth. from the Brazilian Amazon.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaf tea of Hyptis crenata has its practical use in the Brazilian Amazon for treating gastrointestinal and liver disorders, sweating induction, and as an anti-inflammatory. AIM OF THE STUDY: Evaluation of the chemical composition, acute oral toxicity, and antinociceptive and anti-inflammatory activities of the H. crenata essential oil. MATERIAL AND METHODS: The essential oil was hydrodistilled and analyzed by GC and GC-MS. The antinociceptive action in mice was evaluated for the peripheral and central analgesic activity (abdominal contortion and hot plate tests), and the xylene-induced ear swelling was carried out for the nociception test. RESULTS: Oxygenated monoterpenes (53.0%) and monoterpene hydrocarbons (38.9%) predominated in the H. crenata oil, being 1,8-cineo1e (35.9%), α-pinene (20.8%), camphor (10.0%), and ß-pinene (7.3%) their primary constituents. The oral oil administration in the mice did not display changes in behavior patterns or animal mortality at 300 and 2000 mg/kg doses. The control group's biochemical parameters (ALP, AST, ALT) displayed a statistical difference from the treated group, unlike the renal parameters, which showed no variation between the groups. Oil reduced the abdominal contortions at doses of 100 (79.5%) and 300 mg/kg (44.4%), while with endodontacin, the dose was 5 mg/kg (75.2%). In addition, the oil could not decrease the paw licking/biting time at doses of 30, 100, and 300 mg/kg. However, it showed a significant antinociceptive effect on the second phase in the formalin test inhibiting licking time, with a reduction of 50.8% (30 mg/kg), 63.4% (100 mg/kg), 58.0% (300 mg/kg), and morphine (4 mg/kg, 78.3%). The oil administration produced significant inhibition of ear edema at all tested doses, with a better effect produced at 30 mg/kg (64.0% inhibition). CONCLUSION: The oil of Hyptis crenata, rich in 1,8-cineole, camphor, α-pinene, and ß-pinene, totaling 74%, displayed low acute toxicity and significant anti-inflammatory activity, with peripheral and no central antinociceptive action. Thus, these results show an actual perspective on using H. crenata oil in developing a phytotherapeutic product.

A phase 3, randomised, placebo-controlled study of erenumab for the prevention of chronic migraine in patients from Asia: the DRAGON study.

ABSTACT: BACKGROUND: DRAGON was a phase 3, randomised, double-blind, placebo-controlled study which evaluated the efficacy and safety of erenumab in patients with chronic migraine (CM) from Asia not adequately represented in the global pivotal CM study. METHODS: DRAGON study was conducted across 9 Asian countries or regions including mainland China, India, the Republic of Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. Patients (N = 557) with CM (aged 18-65 years) were randomised (1:1) to receive once-monthly subcutaneous erenumab 70 mg or matching placebo for 12 weeks. The primary endpoint was the change in monthly migraine days (MMD) from baseline to the last 4 weeks of the 12-week double-blind treatment phase (DBTP). Secondary endpoints included achievement of ≥ 50% reduction in MMD, change in monthly acute headache medication days, modified migraine disability assessment (mMIDAS), and safety. Study was powered for the primary endpoint of change from baseline in MMD. RESULTS: At baseline, the mean (SD) age was 41.7 (± 10.9) years, and 81.5% (n = 454) patients were women. The mean migraine duration was 18.0 (± 11.6) years, and the mean MMD was 19.2 (± 5.4). 97.8% (n = 545) randomised patients completed the DBTP. Overall, demographics and baseline characteristics were balanced between the erenumab and placebo groups except for a slightly higher proportion of women in the placebo group. At Week 12, the adjusted mean change from baseline in MMD was - 8.2 days for erenumab and - 6.6 days for placebo, with a statistically significant difference for erenumab versus placebo (adjusted mean difference vs placebo: - 1.57 [95%CI: - 2.83, - 0.30]; P = 0.015). A greater proportion of patients treated with erenumab achieved ≥ 50% reduction in MMD versus placebo (47.0% vs 36.7%, P = 0.014). At Week 12, greater reductions in monthly acute headache medication days (- 5.34 vs - 4.66) and mMIDAS scores (- 14.67 vs - 12.93) were observed in patients treated with erenumab versus placebo. Safety and tolerability profile of erenumab was comparable to placebo, except the incidence of constipation (8.6% for erenumab vs 3.2% for placebo). CONCLUSION: DRAGON study demonstrated the efficacy and safety of erenumab 70 mg in patients with CM from Asia. No new safety signals were observed during the DBTP compared with the previous trials. TRIAL REGISTRATION: NCT03867201.

Digoxin at sub-cardiotonic dose modulates the anticonvulsive potential of valproate, levetiracetam and topiramate in experimental primary generalized seizures.

The prevalence of epilepsy in the world population together with a high percentage of patients resistant to existing antiepileptic drugs (AEDs) stimulates the constant search for new approaches to the treatment of the disease. Previously a significant anticonvulsant potential of cardiac glycoside digoxin has been verified by enhancing a weak activity of AEDs in low doses under screening models of seizures induced by pentylenetetrazole and maximal electroshock. The aim of the present study is to investigate the influence of digoxin at a sub-cardiotonic dose on the anticonvulsant activity of valproate, levetiracetam, and topiramate in models of primary generalized seizures with different neurochemical mechanisms. A total of 264 random-bred male albino mice have been used. AEDs were administered 30 min before seizure induction once intragastrically at conditionally effective (ED50) and sub-effective (½ ED50) doses: sodium valproate and topiramate - at doses of 300 and 150 mg/kg; levetiracetam - at doses of 100 and 50 mg/kg. Digoxin was administered once subcutaneously at a dose of 0.8 mg/kg body weight (1/10 LD50) 10-15 min before seizure induction. Picrotoxin (aqueous solution 2.5 mg/kg, subcutaneously), thiosemicarbazide (aqueous solution 25 mg/kg, intraperitoneally), strychnine (aqueous solution 1.2 mg/kg, subcutaneously), camphor (oil solution 1000 mg/kg, intraperitoneally) have been used as convulsive agents for seizure induction. It was found that under the conditions of primary generalized seizures induced by picrotoxin, thiosemicarbazide, strychnine, and camphor, digoxin not only shows its own strong anticonvulsant activity but also significantly enhances the anticonvulsant potential of classical AEDs sodium valproate, levetiracetam, and topiramate. The obtained results substantiate the expediency of further in-depth study of digoxin as an anticonvulsant drug, in particular, the in-depth study of neurochemical mechanisms of its action.

In-vivo and in-vitro effectiveness of three insecticides types for eradication of the tick Rhipicephalus sanguineus in dogs.

Background: External parasites contribute to extensive harmful impacts on their hosts which is why control and eradication of external parasites have been included in all biosecurity plans of dog houses. Aim: To evaluate the in-vitro and in-vivo effectiveness of chemicals like Doramectin injectable and Fipronil 50 mg/ml drops and herbal mixes eco-friendly insecticides like phenylpyrazole-garlic-camphor mix spray for combating the external parasitism in dogs and their influence on the hematological, biochemical, and cortisol (CORT) profiles. Method: The in-vitro effectiveness of the insecticides was conducted by using a total of 216 developmental stage Rhipicephalus sanguineus (72 adults, 72 larvae, and 72 eggs) designed into three replicates of petri dishes (3 plates × 8 units × 3 stages/replicate); each replicate was exposed to 1 ml insecticide. The number of surviving ticks was recorded after 0, 2, 4, 8, 16, and 24 hours. Sixteen Rottweiler male dogs aged 1 year and 45.5 kg were divided into four groups. Three groups (G1, G2, and G3) were experimentally infested with R. sanguineus ticks 3-4 weeks post-dog arrival and kept under observation from zero-time of experimental infestation for 1-2 weeks. The three experimentally infested dog groups were treated with Doramectin injectable, Fipronil 50 mg/ml drops, and phenylpyrazole-garlic-camphor mix spray, respectively, and the fourth group was designed as a negative control. A total of 144 samples, including 48 ethylenediaminetetraacetic acid blood, 48 whole blood, and 48 sera samples, were collected. Results: The in-vitro efficacy revealed highly significant (p < 0.01) 100% killing efficacy that was achieved after 8 hours in Doramectin and Fipronil 50 mg/ml and 24 hours in phenylpyrazole-garlic-camphor mix. The in-vivo trials revealed highly significant (p < 0.01) improvements of red blood cells, hematocrit, mean corpuscular hemoglobin concentrations, platelets, total and differential leukocytic counts, erythrocyte sedimentation rates in the second hour, total protein, creatinine, alanine aminotransferase, urea, glucose, triglycerides, total cholesterol, and CORT levels in the 2-week (P1) and 4-week posttreatment (P2) samples in Dormectin, Fipronil 50 mg/ml, and phenylpyrazole-garlic-camphor mix-treated dogs with more pronounced recovery in phenylpyrazole-garlic-camphor mix spray-treated dogs. Conclusion: The insecticides were able to provide a high level of protection against experimental infestation with concern to the different modes of application. Phenylpyrazole-garlic-camphor mix spray (eco-friendly) achieved higher insecticidal action compared to the chemicals.

Can molecular dynamics explain decreased pathogenicity in mutant camphecene-resistant influenza virus?

ABSTARCTThe development of new anti-influenza drugs remains an active area, and efforts in this direction will likely continue far into the future. In this paper, we present the results of a theoretical study explaining the mechanisms behind the antiviral activity of camphor derivatives. These include camphecene and a number of its analogues. The compounds tested can inhibit hemagglutinin (HA) by binding to it at two possible sites. Moreover, the binding site located at the site of proteolysis is the most important. Serial passaging of influenza in the presence of camphecene leads to the formation of mutation-associated resistance. Specifically, camphecene causes a significant mutation in HA (V615L). This substitution likely reduces the affinity of the compound for the binding site due to steric restriction of the positioning of camphecene in the binding cavity. Molecular dynamics (MD) simulation results show that the mutant HA is a more stable structure in terms of thermodynamics. In other words, launching conformational rearrangements preceding the transition from pre- to post-fusion requires more energy than in wild type HA. This may well explain the lower virulence seen with the camphecene-resistant strain.

Analgesic and anti-inflammatory articular effects of essential oil and camphor isolated from Ocimum kilimandscharicum Gürke leaves.

ETHNOPHARMACOLOGICAL RELEVANCE: Leaves from Ocimum kilimandscharicum Gürke (Lamiaceae) are popularly used against articular pain. AIM OF STUDY: The aim of this study was to test the anti-inflammatory and anti-hyperalgesic (analgesic) properties of the essential oil and camphor isolated from O. Kilimandscharicum leaves (EOOK) in 4 models including zymosan induced-articular inflammation model in mice. MATERIAL AND METHODS: For in vivo models, EOOK was tested in carrageenan-induced paw edema model with oral doses of 30, 100, and 300 mg/kg (oral administration = p.o.) and in zymosan-induced articular inflammation (including knee edema, leukocyte infiltration, mechanical hyperalgesia and nitric oxide), EOOK (100 mg/kg, p. o.) and camphor (30 mg/kg, p. o.) were tested. EOOK (100 mg/kg, p. o.) was tested in the rolling and also in the adhesion of leukocytes to the mesenteric microcirculation in situ model of carrageenan induced inflammation and EOOK (1, 3, 10, 30, and 60 µg/mL) was tested in vitro against neutrophils chemotaxis induced by N-formyl methionyl leucyl phenylalanine (fMLP). RESULTS: The treatment with EOOK significantly inhibited the carrageenan-induced edema, mechanical and cold hyperalgesia. Both, EOOK and camphor inhibited all articular parameters induced by zymosan. In situ intravitral microscopy analysis, EOOK significantly inhibited carrageenan-induced leukocyte rolling and adhesion. In vitro neutrophils chemotaxis, EOOK inhibited the leukocyte chemotaxis induced by fMLP. CONCLUSIONS: The present study showed that EOOK inhibited pain and inflammatory parameters contributing, at least in part, to explain the popular use of this plant as analgesic natural agent. This study also demonstrates that camphor and some known anti-inflammatory compounds present in EOOK could contribute for analgesic and anti-inflammatory articular properties.

The Clinical Effectiveness of Calcium Hydroxide in Root Canal Disinfection of Primary Teeth: A Meta-Analysis.

BACKGROUND The aim of this research was to systematically analyze the effectiveness of calcium hydroxide compared to formocresol (FC) and camphor phenol (CP) in root canal disinfection of primary teeth. MATERIAL AND METHODS The meta-analysis was based on the participants, interventions, control, outcome (PICO) study design principle and 16 randomized-controlled clinical trials published from January 2000 to August 2018. The data heterogeneity of each study was assessed by the Q-test. The odds ratio and 95% confidence interval (CI) were calculated based on the heterogeneity results by Revman software. RESULTS Sixteen randomized-controlled clinical trials of 3047 primary teeth were included in this meta-analysis. There were significant differences of clinical effectiveness between calcium hydroxide and FC in root canal disinfection of primary teeth (OR=3.37; 95% CI range: 2.54-4.48, P<0.01) and endodontic inter-appointment emergencies (EIAE) after disinfection for 7 days (OR=0.26; 95% CI range: 0.16-0.42, P<0.01). However, there was no statistical difference of EIAE, after disinfection of primary teeth for 48 hours, between calcium hydroxide and FC (OR=0.62; 95% CI range: 0.34-1.11, P=0.11). There were significant differences of clinical effectiveness between the calcium hydroxide and CP in root canal disinfection of primary teeth (OR=5.50; 95% CI range: 3.36-8.98, P<0.01). CONCLUSIONS This meta-analysis indicated that the effectiveness of calcium hydroxide as root canal disinfectant in primary teeth was more effective than that of FC and CP.

Blood Pressure and Cognitive Performance After a Single Administration of a Camphor-Crataegus Combination in Adolescents with Low Blood Pressure.

Low blood pressure is rather widespread among adolescents and frequently accompanied by complaints. Two single-center, double-blinded, randomized, and placebo-controlled trials were performed with adolescent participants in the age range of 14 - 17 y having a systolic blood pressure below 118 mmHg (boys) or 110 mmHg (girls). They received a single dose of 20 drops of a fixed combination of natural D-camphor and an ethanolic extract from fresh Crataegus berries (CCC) or of an ethanolic placebo. The efficacy of CCC (commercial name Korodin) has proven its efficacy in the treatment of low blood pressure in adults of all ages, although related placebo-controlled, double-blind studies for adolescents following European (EU) pediatric regulations are lacking. Blood pressure and heart rate were assessed during a rest period, prior to substance administration, 1 min thereafter, and after about 5 min. Additionally, performance was assessed by two cognitive tests. After administration of CCC, a significantly greater rise in blood pressure occurred compared to placebo. In the cognitive tasks, no significant differences were observed. No adverse events or subjective complaints were reported at the final examination; thus, the present study provides evidence for the safety and tolerability of CCC after a single administration.

Inhibition of ß-Secretase Activity by Monoterpenes, Sesquiterpenes, and C13 Norisoprenoids.

Inhibition of ß-secretase (BACE1) is currently regarded as the leading treatment strategy for Alzheimer's disease. In the present study, we aimed to screen the in vitro inhibitory activity of 80 types of aroma compounds (monoterpenes, sesquiterpenes, and C13 norisoprenoids), including plant-based types, at a 200-µM concentration against a recombinant human BACE1. The results showed that the most potent inhibitor of BACE1 was geranyl acetone followed by (+)-camphor, (-)-fenchone, (+)-fenchone, and (-)-camphor with the half-maximal inhibitory concentration (IC50) values of 51.9 ± 3.9, 95.9 ± 11.0, 106.3 ± 14.9, 117.0 ± 18.6, and 134.1 ± 16.4 µM, respectively. Furthermore, the mechanism of inhibition of BACE1 by geranyl acetone was analyzed using Dixon kinetics plus Cornish-Bowden plots, which revealed mixed-type mode. Therefore aroma compounds may be used as potential lead molecules for designing anti-BACE1 agents.

Itch Management: Topical Agents.

Chronic pruritus is a common problem in patients with inflammatory skin diseases as well as in subjects with dry or sensitive skin. Regardless of the underlying cause of the pruritus, a topical therapy is not only useful but most often necessary to achieve symptom control. A good topical therapy should fulfill different functions. An optimal basic therapy based on the condition of the skin is important to repair epithelial barrier defects and to rehydrate the skin. An adequate disease-specific topical therapy is crucial for inflamed skin, e.g. anti-inflammatory topical therapy is an important part in the treatment of atopic dermatitis. Finally, the use of specific antipruritic substances can help to improve pruritus in patients irrespective of the underlying disease. Here, we summarize topical agents used in the treatment of chronic pruritus.

John Brown's system of medicine and its introduction in Denmark around 1800.

At the end of the eighteenth century a scientific basis for medicine was called for. The Scottish physician John Brown proposed an all-comprising medical system in 1780. A surplus or lack of stimulating factors, the prime movers of life according to Brown, was supposed to explain all diseases and indicate their treatment. Individuals only subjected to a small degree of stimulation became affected by "asthenic diseases" which were the most frequent diseases. They should be treated with abundant food and wine, supplemented with camphor, opium, or other drugs considered to be stimulating. Conversely, individuals with "sthenic diseases" should reduce their intake of food and beverage. Brown's system was received with transient approval by some Danish physicians from the late 1790s. But it soon proved to be of no value in medical practice, and its success dwindled within academic medicine around 1814. On the other hand, it seemed to generate new ideas. It became linked with the German Romantic Movement and "Naturphilosophie." The widespread use of camphor and opium in both academic and folk medicine, continued throughout the nine- teenth century and into the twentieth century.

[Raspail, Don Quixote of camphor!]. / Raspail, Don Quichotte du camphre!

François Vincent Raspail (1794-1878) was a chemist and a politician who practised medicine illegally : for him, all pathologies were almost exclusively caused by "parasites" and he treated them all thanks to the beneficial effects of camphor. Raspail did not invent nor discover that substance, which was broadly used in the 18th century, but he codified the use of its various pharmaceutical forms thanks to what would be later called "Raspail's method": camphor to eat (lumps), to snuff (powder), to smoke (cigarettes), brandy and 32° camphored alcohol, camphored oil and sedative water... Since Raspail lavished his patients with many hygiene pieces of advice and moral principles, this method--that was actually a prolongation of his political action in favour of the very poor--was a complete success among the population. But this success was also due to the simplicity of the remedy, its relative harmlessness and, above all, to an incredibly efficient advertising since he enjoyed the support of many important people and also published a very successful book, his Manuel annuaire de Santé, that was re-edited 77 times.

Camphor--a fumigant during the Black Death and a coveted fragrant wood in ancient Egypt and Babylon--a review.

The fragrant camphor tree (Cinnamomum camphora) and its products, such as camphor oil, have been coveted since ancient times. Having a rich history of traditional use, it was particularly used as a fumigant during the era of the Black Death and considered as a valuable ingredient in both perfume and embalming fluid. Camphor has been widely used as a fragrance in cosmetics, as a food flavourant, as a common ingredient in household cleaners, as well as in topically applied analgesics and rubefacients for the treatment of minor muscle aches and pains. Camphor, traditionally obtained through the distillation of the wood of the camphor tree, is a major essential oil component of many aromatic plant species, as it is biosynthetically synthesised; it can also be chemically synthesised using mainly turpentine as a starting material. Camphor exhibits a number of biological properties such as insecticidal, antimicrobial, antiviral, anticoccidial, anti-nociceptive, anticancer and antitussive activities, in addition to its use as a skin penetration enhancer. However, camphor is a very toxic substance and numerous cases of camphor poisoning have been documented. This review briefly summarises the uses and synthesis of camphor and discusses the biological properties and toxicity of this valuable molecule.

Antimicrobial efficacy of chlorhexidine and calcium hydroxide/camphorated paramonochlorophenol on infected primary molars: a split-mouth randomized clinical trial.

OBJECTIVE: To compare via a split-mouth randomized clinical trial the efficacy of 1% chlorhexidine gel, calcium hydroxide/camphorated paramonochlorophenol (Callen PMCC), and a one-visit endodontic treatment against mutans streptococci and anaerobic bacteria found in primary molars with necrotic pulps and to assess clinical success rates after 12 months. METHOD AND MATERIALS: Pre- and posttreatment intracanal samples were collected from 37 teeth (from 21 children) for analysis of the number of mutans streptococci and anaerobic bacteria. Clinical and radiographic criteria were analyzed to determine treatment outcome. RESULTS: Chlorhexidine gel significantly reduced mutans streptococci levels (P = .010), whereas Callen PMCC significantly reduced the levels of anaerobic bacteria (P = .002). No differences in the reduction of mutans streptococci (P = .187) and anaerobes (P = .564) were observed between groups. The clinical success rates were 85.71% (Callen PMCC), 78.57% (chlorexidine gel), and 77.77% (one-visit treatment). CONCLUSION: Teeth treated with Callen PMCC presented the highest clinical success rate. The 1% chlorhexidine gel, as well as calcium hydroxide/camphorated paramonochlorophenol, presented limited efficacy in reducing bacteria from necrotic primary root canals.

Salvia Lavandulifolia Vahl: características botánicas, composición química y actividad biológica / Salvia Lavandulifolia Vahl: botanical characteristics, chemical composition and biological activity

El objetivo de este trabajo es realizar una revisión sobre la especie Salvia lavandulifolia, conocida como salvia española, perteneciente a la familia de las Lamináceas y característica de la zona mediterránea. Presenta una gran complejidad taxonómica, reflejada en las cinco subespecies que se conocen: lavundulifolia, vellerea, oxyodon, blancoana y mariolensis. En su composición química es característica la presencia de polifenoles y terpenos, especialmente monoterpenos como alpha-pineno, 1,8-cineol y alcanfor, frecuentemente en elevado porcentaje en su aceite esencial. Esta especie forma parte de un importante género de plantas aromáticas aclimatadas en todo el mundo por su uso en medicina tradicional (antibacteriano, digestivo, reforzador de la memoria) y también con proósitos culinarios. Se han publicado diversos estudios relacionados con su actividad farmacológica que demuestran sus propiedades antioxidante, antiinflamatoria, estrogénica, inhibidora de la acetilcolinesterasa, así como su eficacia en afecciones del sistema nervioso central, como trastornos cognitivos (AU)

The aim of this paper es to review Salvia lavandulifolia, known as Spanish sage, belonging to the Lamiaceae family and characteristic of the Mediterranean área. It shows high taxonomic complexity reflected in the five known subspecies: lavandulifolia, vellerea, oxyodon, clancoana and mariolensis. Its chemical composition is characterized by the presence of polyphenols and terpenes, particularly monoterpenes such as alpha-pinene, 1,8-cineole, and camphor, which are often found in high percentage in the essential oil. This species belongs to an important genus of aromatic plants acclimated worldwide and used traditionally in medicine (as antibacterial, digestive and memory enhacer) as well as for culinary purposes- There are several pharmacological studies showing its antioxidant, anti-inflammatory, estrogenic and acetylcholinesterase inhibition properties, as well as its efficacy in central nervous system diseases as cognitive disorders (AU)

The birth of convulsive therapy revisited: a reappraisal of László Meduna's first cohort of patients.

BACKGROUND: The introduction of convulsive therapy (COT) was undoubtedly one of the milestones in the history of psychiatry. Its originator, László Meduna, has become one of the founding fathers of biological psychiatry. METHODS: In his first major publication on COT, Meduna described the short-term treatment outcome of the first 26 schizophrenia patients who underwent camphor- or cardiazol-induced COT; 10 improved significantly, 3 appeared slightly improved, and 13 were unimproved. The original medical notes of 23 of the 26 patients were recently recovered and the patients re-diagnosed by the authors employing ICD-10 criteria. RESULTS: The diagnosis of schizophrenia was confirmed in 15 cases (all but two of them involving prominent catatonic symptomatology), while 2 cases met diagnostic criteria for schizoaffective disorder, 3 for Bipolar Affective Disorder (BAD) with psychotic features, 1 for psychotic depression, and 1 for Acute and Transient Psychotic Disorder (ATPD). In a final case, the most probable diagnosis was schizophrenia. Scrutiny of the notes revealed that 4 schizophrenia patients evidenced slight improvement on COT and in one case the improvement was only transient. A limitation of this study is that the quality of the original files varied considerably and the re-evaluation was done retrospectively. CONCLUSIONS: A very broad concept of schizophrenia in the 1930s explains the discrepancy between the original and the revised results. In line with the current views on the effectiveness of electroconvulsive therapy, catatonic symptoms, but not the core schizophrenic process, showed some improvement while all ATPD, BAD and depressed patients responded to COT.

[Camphor poisoning following ingestion of mothballs 'for headache']. / Kamferintoxicatie na inname van mottenballen 'wegens hoofdpijn'.

BACKGROUND: Camphor is a toxic hydrocarbon, found in numerous over-the-counter medicinal products and chemist-shop items. The consequences of camphor poisoning depend on the dose, and severe poisoning can result in death. Ingestion of camphor can cause seizures, apnoea, renal insufficiency, raised hepatic enzyme levels, and vomiting resulting in chemical pneumonitis due to aspiration. CASE DESCRIPTION: We present the case of a 34-year-old female patient from the Dominican Republic who was brought into our accident and emergency department following the ingestion of camphor mothballs for persisting headaches. She was unconscious (Glasgow coma score: 3) and had severe acidosis (pH 6.59), respiratory insufficiency, electrolyte imbalance and raised hepatic enzyme and amylase levels. She was admitted to the intensive care unit and recovered quickly. Five days later, she was transferred to a general ward, where it became apparent that she was suffering from severe memory loss. After eight days she was discharged in good clinical condition, although she still suffered some memory loss. CONCLUSION: Many every-day products contain camphor. Poisoning can lead to an acute clinical picture, and immediate intensive care department treatment is obligatory. As there is no antidote available, supportive care is the only available option when poisoning occurs.

Further antinociceptive effects of myricitrin in chemical models of overt nociception in mice.

The present work explored the antinociceptive effects of the flavonoid myricitrin in models of overt nociception triggered by intraplantar injection of chemical algogens into the hind paw of mice. The nociception induced by bradykinin (3 nmol/paw i.pl.) was abolished by prior treatment with myricitrin (10-100mg/kg, i.p.) with ID(50) of 12.4 (8.5-18.1)mg/kg. In sharp contrast, myricitrin failed to affect the nociception elicited by prostaglandin E(2) (3 nmol/paw i.pl.). Cinnamaldehyde (10 nmol/paw i.pl.)-induced nociception was reduced by myricitrin (100mg/kg, i.p.) and camphor (7.6 mg/kg,s.c.) in 43±10% and 57±8%, respectively. Myricitrin (30-100mg/kg, i.p.) and amiloride (100mg/kg, i.p.) inhibited nociceptive responses induced by acidified saline (pH 5/paw i.pl.), with ID(50) of 22.0 (16.1-30.0)mg/kg and inhibition of 71±6% and 64±5%, respectively. Moreover, myricitrin (10-30 mg/kg, i.p.) and ruthenium red (3mg/kg, i.p.) significantly reduced the nociception induced by menthol (1.2 µmol/paw i.pl.) with the mean ID(50) of 2.4 (1.5-3.7)mg/kg and inhibition of 95±3% and 51±7%, respectively. In addition, myricitrin administration (30 and 100mg/kg, i.p.) markedly reduced menthol-induced mechanical allodynia. However, myricitrin (100mg/kg, i.p.) prevented (only in time of 60 min) cold allodynia induced by menthol. Collectively, the present results extend prior data and show that myricitrin promotes potent antinociception, an action that is likely mediated by an inhibition of the activation of nociceptors by bradykinin and TRPs agonist (i.e. cinnamaldehyde, acidified saline and menthol), probably via inhibition of PKC pathways. Thus, myricitrin could constitute an attractive molecule of interest for the development of new analgesic drugs.