Cannabinoid therapeutics in orofacial pain management: a systematic review.

The objective of this paper was to investigate the published evidence regarding effects of cannabinoids (natural and synthetic) on post-operative and/or out-of-office pain management in patients suffering from orofacial pain that presents in the dental setting. Three online databases (Ovid (MEDLINE), PubMed (MEDLINE), Scopus) were searched (July 2021). Additional studies were sought through grey literature searching (Cochrane Library Trials and ClinicalTrials.gov) and hand-searching the reference lists of included articles. All studies that analysed cannabinoid products and pain management of conditions that present in the general or specialist dental setting in the English language were included. Of the five articles included, one reported a significant effect on temporomandibular disorder pain relief using a topical cannabidiol formulation compared to a placebo. Four articles reported no significant effects of cannabinoids for pain management across various orofacial pain conditions. Although one study reported a positive effect, insufficient evidence exists to support a tangible clinical benefit of cannabinoids in managing orofacial pain, further research is recommended to investigate the benefits of cannabinoids' use. © 2022 Australian Dental Association.

The use of topical anaesthetic in the banding of internal haemorrhoids: a feasibility study for a randomised control trial.

INTRODUCTION: Rubber band ligation (RBL) is a procedure commonly performed in colorectal clinics for internal haemorrhoids. Overall, 90% of patients experience pain following RBL. We aimed to complete a feasibility randomised control trial assessing the role of topical anaesthetic before RBL of internal haemorrhoids. METHODS: We performed a prospective, single-centre, single blinded, randomised (1:1) control feasibility trial. Patients presenting with symptomatic haemorrhoids suitable for banding were randomised to undergo the procedure with local anaesthetic or without (control). Pain scores and vasovagal symptoms were assessed at 0 minutes, 30 minutes, 4 hours and 72 hours after the procedure. Primary outcome measures were recruitment rate, participant retention rate and patient and surgeon acceptability. Secondary outcome measures were pain scores up to 72 hours, vasovagal episodes, new use of analgesia and adverse outcomes. RESULTS: In total, 35 patients (18 topical anaesthetic, group A; 17 no anaesthetic gel, group B) were recruited. Mean recruitment rate was 11.7 participants per month. Thirty-three (94%) participants remained in the study until completion, with two patients lost to telephone follow-up. The treatment was acceptable for 35 (97%) eligible patients. One patient declined enrolment. The treatment was acceptable to all surgeons (100%). There was a significant difference in median pain scores of -2 (95% CI -4.0 to -1.0, p=0.0006) at the 30-minute time point only. There was no significant difference in vasovagal symptoms (p=0.10) or new analgesia use (p=0.85). CONCLUSION: We have shown that a phase III clinical trial is feasible for assessing the role of topical anaesthetic before RBL of internal haemorrhoids. We have demonstrated excellent patient recruitment and retention as well as patient and surgeon acceptability.

Jellyfish venom proteins and their pharmacological potentials: A review.

Several research in the organisms of marine invertebrates to assess the medicinal ability of its bio-active molecules have yielded very positive results in recent times. Jellyfish secreted venoms are rich sources of toxins intended to catch prey or deter predators among invertebrate species, but they may also have harmful effects on humans. The nematocyst, a complex intracellular system that injects a venomous mixture into prey or predators that come into contact with the tentacles or other parts of the body of cnidarians, determines the venomous existence of cnidarians. Nematocyst venoms are mixtures of peptides, proteins and other components that in laboratory animals can induce cytotoxicity, blockade of ion channels, membrane pore formation, in vivo cardiovascular failure and lethal effects. There are also valuable pharmacological and biological aspects of jellyfish venoms. In the present review, overviews of the variety of possible toxin families in cnidarian venoms are addressed in this analysis and these potential toxins are surveyed with those from other cnidarians that offer insight into their potential functions such as anti-oxidant, anti-cancer activity and much more. This research review will provide awareness of the growing repertoire of jellyfish venom proteins and will help to further isolate and classify particular proteins to understand its structure and functional relationship.

A sustainable approach for graphene-oxide surface decoration using Oxalis corniculata leaf extract-derived silver nanoparticles: their antibacterial activities and electrochemical sensing.

In this work, a facile green synthesis using Oxalis corniculata leaf extract (OCLE) as a biodegradable reducing and capping/stabilizing agent was carried out for the construction of Oxalis corniculata leaf extract-derived silver nanoparticles (OCLE-AgNPs). Moreover, OCLE-AgNPΔGO nanocomposites were fashioned simply by mixing a GO suspension and supernatant OCLE-AgNPs via a one-pot environmentally benign method. The AgNPΔGO nanocomposites are biocompatible materials for potential applications such as antibacterial activities against two different types of bacterial cells, namely Gram-positive Bacillus subtilis and Gram-negative Escherichia coli and selective electrochemical sensing to itraconazole (ITRA) at the fabricated GCE (AgNPΔGO@GCE). AgNPΔGO@GCE sensors gave excellent outcomes for ITRA as higher current response over the bare GCE. Under optimized conditions, the oxidation peak current of ITRA varied linearly with a wide range of the concentration between 26.7 µM and 103.8 µM with a correlation coefficient of 0.997 and a detection limit of 0.1276 µM, for differential pulse anodic stripping voltammetric (DP-ASV) technique. In addition, the possible mechanism for the ITRA oxidation was further verified and explained by single-electron transfer (SET) and proton removal mechanism steps. The developed sensor exhibited good repeatability, reproducibility, and stability. The use of environmentally benign and renewable plant material offers enormous benefits of eco-friendliness applicability.

Pharmacophore modelling, atom-based 3D-QSAR generation and virtual screening of molecules projected for mPGES-1 inhibitory activity.

COX-2 inhibitors exhibit anticancer effects in various cancer models but due to the adverse side effects associated with these inhibitors, targeting molecules downstream of COX-2 (such as mPGES-1) has been suggested. Even after calls for mPGES-1 inhibitor design, to date there are only a few published inhibitors targeting the enzyme and displaying anticancer activity. In the present study, we have deployed both ligand and structure-based drug design approaches to hunt novel drug-like candidates as mPGES-1 inhibitors. Fifty-four compounds with tested mPGES-1 inhibitory value were used to develop a model with four pharmacophoric features. 3D-QSAR studies were undertaken to check the robustness of the model. Statistical parameters such as r2 = 0.9924, q2 = 0.5761 and F test = 1139.7 indicated significant predictive ability of the proposed model. Our QSAR model exhibits sites where a hydrogen bond donor, hydrophobic group and the aromatic ring can be substituted so as to enhance the efficacy of the inhibitor. Furthermore, we used our validated pharmacophore model as a three-dimensional query to screen the FDA-approved Lopac database. Finally, five compounds were selected as potent mPGES-1 inhibitors on the basis of their docking energy and pharmacokinetic properties such as ADME and Lipinski rule of five.

Quercetin attenuates neuronal death against aluminum-induced neurodegeneration in the rat hippocampus.

Aluminum is a light weight and toxic metal present ubiquitously on earth, which has gained considerable attention due to its neurotoxic effects. It also has been linked ecologically and epidemiologically to several neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Guamanian-Parkinsonian complex and Amyotrophic lateral sclerosis (ALS). The mechanism of aluminum neurotoxicity is poorly understood, but it is well documented that aluminum generates reactive oxygen species (ROS). Enhanced ROS production leads to disruption of cellular antioxidant defense systems and release of cytochrome c (cyt-c) from mitochondria to cytosol resulting in apoptotic cell death. Quercetin (a natural flavonoid) protects it from oxidative damage and has been shown to decrease mitochondrial damage in various animal models of oxidative stress. We hypothesized that if oxidative damage to mitochondria does play a significant role in aluminum-induced neurodegeneration, and then quercetin should ameliorate neuronal apoptosis. Administration of quercetin (10 mg/kg body wt/day) reduced aluminum (10 mg/kg body wt/day)-induced oxidative stress (decreased ROS production, increased mitochondrial superoxide dismutase (MnSOD) activity). In addition, quercetin also prevents aluminum-induced translocation of cyt-c, and up-regulates Bcl-2, down-regulates Bax, p53, caspase-3 activation and reduces DNA fragmentation. Quercetin also obstructs aluminum-induced neurodegenerative changes in aluminum-treated rats as seen by Hematoxylin and Eosin (H&E) staining. Further electron microscopic studies revealed that quercetin attenuates aluminum-induced mitochondrial swelling, loss of cristae and chromatin condensation. These results indicate that treatment with quercetin may represent a therapeutic strategy to attenuate the neuronal death against aluminum-induced neurodegeneration.

Role of computed tomography (CT) scan in staging of cervical carcinoma.

BACKGROUND & OBJECTIVES: Staging of cervical carcinoma is done clinically using International Federation of Obstetrics and Gynecology (FIGO) guidelines. It is based on physical examination findings and also includes results of biopsy, endoscopy and conventional radiological tests like chest radiograph, intravenous urography and barium enema. These conventional radiological investigations have largely been replaced by computed tomography (CT) and magnetic resonance imaging (MRI) at present. FIGO staging system does not consider CT and MRI mandatory; however, use of these modalities are encouraged. This prospective study was conducted to determine the role of CT in staging work up in women diagnosed with cervical carcinoma. METHODS: Fifty three women diagnosed with cervical carcinoma were evaluated with contrast enhanced CT scan of abdomen and pelvis. CT scan images were especially evaluated to determine tumour size, invasion of parmetrium, pelvic walls, rectum, urinary bladder and ureters, pelvic or retroperitoneal lymphadenopathy and distant metastases. CT findings were associated with clinical findings and staging, including findings from cystoscopy and sigmoidoscopy. RESULTS: There was a poor agreement between clinical and CT staging of cervical carcinoma. Primary tumour was demonstrated on CT in 36 (70%) of 53 patients. CT underestimated the parametrial, vaginal and pelvic wall invasion when compared with physical examination. CT overestimated the urinary bladder and rectal invasion when compared with cysto-sigmoidoscopy, however, CT had 100 per cent negative predictive value (NPV) to exclude bladder and rectal involvement. CT detection of lymph node enlargement and lung metastases influenced the management. INTERPRETATION & CONCLUSIONS: Our findings show that CT scan does not reliably correlate with clinical FIGO staging of cervical cancer. However, it can detect urinary obstruction as well as nodal or distant metastases and thus improves the clinical FIGO staging.

Comparative evaluation of the remineralising effects and surface microhardness of glass ionomer cement containing grape seed extract and casein phosphopeptide - amorphous calcium phosphate: an in vitro study.

AIM: To evaluate and compare in vitro the remineralising effects and surface microhardness of glass ionomer cement (GIC), GIC containing grape seed extract and GIC containing casein phosphopeptide-amorphous calcium phosphate (CPP-ACP). METHODS: An in vitro study with 45 mandibular premolars with standardised class V cavities prepared on the buccal and lingual surfaces. Artificial caries-like lesions were created and teeth were randomly divided into 3 groups of 15 teeth each. Each tooth was sectioned longitudinally into buccal and lingual halves; lingual half was used as control and the other as the test specimen. Axial longitudinal sections of the control specimens were analysed under polarised light microscopy. The experimental halves were restored with 3 materials. Group I: glass ionomer cement (GIC), Group II: 10% (w/w) grape seed extract and GIC (GSGIC), Group III: 10% (w/w) casein phosphopeptide-amorphous calcium phosphate (Recaldent) and GIC (CPPGIC). The restored tooth specimens were exposed to pH cycling for 28 days and analysed again for remineralisation under polarised microscopy. For the second part of the study, 60 cylindrical specimens (20 each) were made using standardised brass moulds and the three experimental materials. The specimens were immersed individually in de-ionised water. After 7 days of immersion, 10 specimens from each group were subjected to microhardness measurements and repeated on the remaining specimens at the end of 30 days. STATISTICS: One way ANOVA and post-hoc Tukey's test were used for statistical analysis. RESULTS: CPPGIC showed the greatest remineralisation followed by GSGIC and least for GIC. Comparisons of microhardness between the three groups were not statistically significant. CONCLUSION: Grape seed extract and CPPACP can be used for remineralisation of damaged dentine and their incorporation into GIC does not compromise the microhardness properties significantly.

Ergonomic evaluation of conventional and improved methods of aonla pricking with women workers.

Conventional and improved methods of aonla pricking were evaluated ergonomically on an experiment conducted for 20 minute with women workers. The working heart rate, energy expenditure rate, total cardiac cost of work and physiological cost of work with conventional tools varied from 93-102 beats.min-1, 6-7.5 kJ.min-1, 285-470 beats, 14 -23 beats.min-1 while with machine varied from 96-105 beats.min-1, 6.5-8 kJ.min-1 , 336-540 beats, 16-27 beats.min-1 respectively. OWAS score for conventional method was 2 indicating corrective measures in near future while with machine was 1 indicating no corrective measures. Result of Nordic Musculoskeletal Questionnaire revealed that subjects complaint of pain in back, neck, right shoulder and right hand due to unnatural body posture and repetitive movement with hand tool. Moreover pricking was carried out in improper lighting conditions (200-300 lux) resulting into finger injuries from sharp edges of hand tool, whereas with machine no such problems were observed. Output with machine increased thrice than hand pricking in a given time. Machine was found useful in terms of saving time, increased productivity, enhanced safety and comfort as involved improved posture, was easy to handle and operate, thus increasing efficiency of the worker leading to better quality of life.

Chemometrics evaluation of the herbal drug Andrographis paniculata.

A fingerprint was developed to evaluate ten genotypes of Andrographis paniculata (a herbal drug) collected from different geographical locations. The genotypes were assessed by HPLC and the chromatogram areas were used to construct fingerprints. Between the two fingerprints, vector of differences was defined. The scalar mean of the deviated vector was used for statistical analysis. By incorporating appropriate chemometric methods better differentiation of samples was achieved. This provides tools for extracting relevant chemical information from the obtained data. The developed method can be used as a quality control tool for rapid authentication, identity, assessment and selection of good quality natural drug from a wide variety of herbal samples.

Dynamics of pesticide residues in nectar and pollen of mustard (Brassica juncea (L.) Czern.) grown in Himachal Pradesh (India).

Residues dynamics of Endosulfan (525.00 g a.i. ha(-1)), Imidacloprid seed treatment (21 g a.i. kg(-1)), Lambdacyhalothrin (75.00 g a.i. ha(-1)) and Spiromesifen (225.00 g a.i. ha(-1)) in nectar and pollen of mustard, Brassica juncea (L.) Czern. grown in Himachal Pradesh (India) were determined through bioassay (using Drosophila melanogaster Meig. as test organism) and GC (Gas chromatographic) and HPLC (High performance liquid chromatographic) methods. In general chromatographic methods were more sensitive for the determination of above given pesticides compared to bioassay method. Average recoveries in nectar samples varied between 82.85 and 88.90% by bioassay and 91.20 and 93.55% by chromatographic techniques. In pollen samples, recoveries varied between 81.44 and 86.44% by bioassay and 88.50 and 91.30% by chromatographic methods. Imidacloprid residues were neither found in nectar nor in pollen samples at the time of sampling i.e. 50% of flowering. The order of average half life of residues was: Lambdacyhalothrin (12.45 h) < Spiromesifen (19.99 h) < Endosulfan (27.49 h) for nectar and Spiromesifen (9.69 h) < Lambdacyhalothrin (12.44 h) < Endosulfan (17.84 h) for pollen samples. It was found that Imidcloprid seed treatment was practically harmless to honey bees, whereas a waiting period of 5 days must be observed on crops sprayed with these chemicals during blooms to avoid any accidental hazards to honey bees.

Targeting HIV-1 through molecular modeling and docking studies of CXCR4: leads for therapeutic development.

The chemokine receptor CXCR4 is the receptor for several chemokines and major co-receptor for X4 human immunodeficiency virus type-1 strains entry into cell. A three-dimensional model of human CXCR4 was developed by homology modeling using the high-resolution bovine rhodopsin structure as template. Interactions between CXCR4 and flavonoids were investigated using in silico docking studies. The results underscore the potential of these compounds that they may become important new antiviral drugs to combat AIDS. It is worth mentioning also that apart from these existing flavonoids, there are many new compounds that may also be useful as topical agents to inactivate virus, or may act as adjuvants with other antiviral drugs.

Meglumine Eicosapentaenoic acid (MeEPA) a new soluble omega-3 fatty acid formulation: in vitro bladder cancer cytotoxicity tests in combination with epirubicin and mitomycin.

OBJECTIVE: To determine if Meglumine-Eicosapentaenoic Acid (MeEPA) acts synergistically with epirubicin and mitomycin to enhance cytotoxicity towards bladder cancer cell lines in vitro. MATERIALS AND METHODS: Bladder cancer cells were exposed to MeEPA in combination with epirubicin or mitomycin. Residual viable cell biomass was estimated with the methyl-thiazoldiphenyl tetrazolium (MTT) assay following drug exposure. Drug interaction was analysed using median effect analysis to determine levels of synergism. RESULTS: Most combinations of MeEPA with both epirubicin and mitomycin showed a high-level of synergism. At high doses, drug precipitation adversely affected MTT assay analysis suggesting antagonism of action. However, the predominant pattern was of synergism for most dose combinations tested. CONCLUSION: Bladder cancer treated by endoscopic resection alone is subject to high recurrence rates. Post-operative intravesical instillation of epirubicin and mitomycin can halve recurrence rates, but there is no evidence that disease progression to invasive bladder cancer is altered. Thus, optimisation of current treatment strategies is required. The anti-tumour activity of fatty acids is well established and MeEPA is a new, soluble formulation with the potential to enhance intravesical drug efficacy.

The release dynamics of model drugs from the psyllium and N-hydroxymethylacrylamide based hydrogels.

In order to utilize the psyllium husk, a medicinally important natural polysaccharide, for developing the novel hydrogels for the controlled drug delivery device, we have prepared psyllium and N-hydroxymethylacrylamide based polymeric networks by using N,N'-methylenebisacrylamide (N,N'-MBAAm) as crosslinker. The polymeric networks thus formed were characterized with scanning electron micrography (SEM), FTIR and thermogravimetric analysis (TGA) techniques to study various structural aspects of the networks and also with the swelling response of the polymeric networks as a function of time, temperature, pH and [NaCl]. Equilibrium swelling has been observed to depend on both structural aspects of the polymers and environmental factors. Maximum P(s) 748.3 was observed at 13.0 x 10(-3)mol/L of [N,N'-MBAAm] in 0.5M NaOH solution. The release dynamics of model drugs (salicylic acid and tetracycline hydrochloride) from hydrogels has also been discussed, for the evaluation of the release mechanism and diffusion coefficients. The effect of pH on the release pattern of tetracycline has been studied by varying the pH of the release medium. In release medium of pH 7.4 buffer the release pattern of tetracycline drastically changes to the extent that mechanism of drug diffusion shifted from non-Fickian diffusion to Fickian diffusion. It has been observed that diffusion exponent "n" have 0.71, 0.67 and 0.52 values and gel characteristic constant 'k' have 1.552 x 10(-2), 2.291 x 10(-2) and 5.309 x 10(-2) values in distilled water, pH 2.2 buffer and pH 7.4 buffer, respectively, for tetracycline release. In solution of pH 7.4 buffer, the rate of polymer chain relaxation was more as compare to the rate of drug diffusion from these hydrogels and it follows Fick's law of diffusion. The value of the initial diffusion coefficient for the release of tetracycline hydrochloride was higher than the value of late time diffusion coefficient in each release medium indicating that in the start, the diffusion of drug from the polymeric matrix was fast as compare to the latter stages.

The economic impact of visceral leishmaniasis on households in Bangladesh.

OBJECTIVES: To explore current patterns of diagnosis and treatment, quantify household economic impact and identify household strategies to cover the costs of visceral leishmaniasis (VL) care in rural Bangladesh. METHOD: Structured interviews with 113 VL patients from 87 households documenting all provider visits and expenditures for health care for VL, and the ways in which the expenditures were covered. RESULTS: Patients paid a median of 7 visits to six different providers before beginning VL treatment. All visited the subdistrict government hospital at least once. While health care, including antileishmanial drug therapy, is officially available free of charge at government facilities, 79% of patients reported making informal payments for provider access, diagnostics and drug administration; only 14% of patients received their full drug course from this source. For the 58% of patients who purchased the full treatment course, drug cost constituted 34% of direct expenditure. Median direct expenditure for one VL patient was US$87 and median income lost was $40; median total expenditure was 1.2 times annual per capita income of our study population. Households employed multiple coping strategies to cover expenditures, most commonly sale or rental of assets (62%) and taking out loans (64%). CONCLUSIONS: Visceral leishmaniasis treatment causes a major economic burden in affected families. Control strategies for VL should facilitate timely, affordable diagnosis and treatment of patients to decrease the infection reservoir and to alleviate the economic burden of VL on households.

Production of solasodine by Solanum laciniatum using plant tissue culture technique.

Leaf and hypocotyl explants of 15 days old aseptically grown seedlings of Solanum laciniatum were cultured on MS medium supplemented with NAA (2 mg/l) and kinetin (0.5 mg/l) for callus initiation. For maintenance and proliferation of callus MS medium supplemented with 2,4-D (1 mg/l) and kinetin (0.5 mg/l) was used. The growth of the calli derived from hypocotyls increased with time of incubation and remained almost constant after 45 days. The solasodine content in callus culture was maximum after 30 days of incubation. Addition of L-arginine in the medium (50-150 mg/l) increased growth as well as chlorophyll content in the callus culture. The solasodine content also increased up to 1.2 to 1.4 times in these cultures. High frequency shoot regeneration was obtained in MS medium having BA (4 mg/l) and IBA (0.25 mg/l). For shoot multiplication, MS medium having BA (4 mg/l) was used. Shoots rooted on the same medium. Organogenesis promoted solasodine accumulation in the cultures. Regenerated shoots yielded higher solasodine content than undifferentiated as well as organogenic callus. Solasodine contents in the regenerated shoots was found to be 10 times higher than the callus culture and approached towards the field grown plants. Thin layer chromatography revealed the presence of three compounds. The most predominant spot (Rf 0.789) corresponded to the reference solasodine.

Hypolipidemic effect of different extracts of Clerodendron colebrookianum Walp in normal and high-fat diet fed rats.

Clerodendron colebrookianum Walp (family, Verbenaceae) has been used as a home remedy by the Mizo people of north eastern (NE) region of India in their folklore medicine as a cardioprotective (mainly against high blood pressure) agent. The scientific basis for their use has yet to be established. Therefore, in this investigation an attempt has been made to study the effect of different extracts of the leaves of Clerodendron colebrookianum Walp (CC) on serum lipid profile which is closely associated with many cardiovascular diseases. It was found that after administration of both crude and organic extracts the serum lipid profile, i.e. total cholesterol (TC), triglycerides (TG) and low density lipoprotein (LDL) lowered significantly (P<0.001) from their respective control except TG in methanol extract (ME)-treated rats. The decreased percentage of TC, TG and LDL after administration of crude extract (CE) and ethylacetate extract (EE) with normal diet were found to be 35, 39 and 48%, and 33, 18 and 91%, respectively, after 7 days of treatment. In case of ME the lowering of TC and LDL were noted to be 41 and 85%, respectively. Both TC and TG were lowered significantly (P<0.001) even after the administration of crude extract against high-fat diet. Significant increase of cardioprotective lipid, i.e high density lipoprotein (HDL) after administration of EE (46%) and ME (38%) was another interesting finding of this experiment. Total cholesterol:HDL and LDL:HDL ratios were significantly lower in the experimental group. Therefore, it was concluded that the leaves of CC have definite cardioprotective potentiality, and there is a valid scientific basis for consuming it for better health in NE region of India.

Genetic transformation of Robinia pseudoacacia by Agrobacterium tumefaciens.

Transgenic Robinia pseudoacacia plants were obtained by Agrobacterium tumefaciens mediated gene transfer. Agrobacterium strain LBA4404 harbouring a binary vector that contained the chimeric neomycin phosphotransferase II (NPTII) and beta-glucuronidase (GUS) genes was co-cultivated with hypocotyl segments of in vitro raised seedlings of Robinia. Parameters important for high efficiency regeneration and transformation rates included type of explant, pre-conditioning of explants and appropriate length of co-cultivation period with Agrobacterium. A transformation frequency 16.67% was obtained by 48 hr of pre-conditioning followed by 48 hr of co-cultivation. Transformed tissue was selected by the ability to grow on kanamycin containing medium. Successful regeneration was followed after histochemical GUS assay for the detection of transgenic tissue. This transformation procedure has the potential to expand the range of genetic variation in Robinia.