A randomised Trial of Autologous Blood products, leukocyte and platelet-rich fibrin (L-PRF), to promote ulcer healing in LEprosy: The TABLE trial.

INTRODUCTION: Autologous blood products like Platelet Rich Plasma (PRP) and Leukocyte and Platelets Rich Fibrin (L-PRF) have been used for many years across many types of skin ulcers. However, the effectiveness of autologous blood products on wound healing is not well established. METHODS: We evaluated the 'second generation' autologous product- Leukocyte and Platelet- Rich Fibrin (L-PRF). Our trial was undertaken on patients suffering from neuropathic leprosy ulcers at the Anandaban hospital which serves the entire country of Nepal. We conducted a 1:1 (n = 130) individually randomised trial of L-PRF (intervention) vs. normal saline dressing (control) to compare rate of healing and time to complete healing. Rate of healing was estimated using blind assessments of ulcer areas based on three different measurement methods. Time to complete healing was measured by the local unblinded clinicians and by blind assessment of ulcer images. RESULTS: The point estimates for both outcomes were favourable to L-PRF but the effect sizes were small. Unadjusted mean differences (intervention vs control) in mean daily healing rates (cm2) were respectively 0.012 (95% confidence interval 0.001 to 0.023, p = 0.027); 0.016 (0.004 to 0.027, p = 0.008) and 0.005 (-0.005 to 0.016, p = 0.313) across the three measurement methods. Time to complete healing at 42 days yielded Hazard Ratios (unadjusted) of 1.3 (0.8 to 2.1, p = 0.300) assessed by unblinded local clinicians and 1.2 (0.7 to 2.0, p = 0.462) on blind assessment. CONCLUSION: Any benefit from L-PRF appears insufficient to justify routine use in care of neuropathic ulcers in leprosy. TRIAL REGISTRATION: ISRCTN14933421. Date of trial registration: 16 June 2020.

Autologous blood products: Leucocyte and Platelets Rich Fibrin (L-PRF) and Platelets Rich Plasma (PRP) gel to promote cutaneous ulcer healing - a systematic review.

OBJECTIVE: To summarise evidence on the effectiveness of Platelet-Rich Plasma (PRP) gel and Leucocyte and Platelet Rich Fibrin (L-PRF) gel as agents promoting ulcer healing compared with the standard wound dressing techniques alone. DESIGN: Systematic review. ELIGIBILITY CRITERIA: Individual patient randomised controlled trials on skin ulcers of all types excluding traumatic lesions.Intervention group: treatment with topical application of L-PRF gel or PRP gel to the wound surface. CONTROL GROUP: treatment with standard skin ulcer care using normal saline, normgel or hydrogel dressings. INFORMATION SOURCES: Medline (Ovid), Excerpta Medica Database (EMBASE), Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL) and Web of Science and manual search of studies from previous systematic reviews and meta-analyses. The papers published from 1946 to 2022 with no restriction on geography and language were included. The last date of the search was performed on 29 August 2022. DATA EXTRACTION AND SYNTHESIS: Independent reviewers identified eligible studies, extracted data, assessed risk of bias using V.2 of the Cochrane risk-of-bias tool for randomised trials tool and assessed certainty of evidence by using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. MAIN OUTCOME MEASURES: Time to complete healing, proportion healed at a given time and rate of healing. RESULTS: Seven studies met the inclusion criteria, five using PRP gel and two using L-PRF gel. One study showed a better proportion of complete healing, three reported reduced meantime to complete healing and five showed improved rate of healing per unit of time in the intervention group. The risk of bias was high across all studies with one exception and the GRADE showed very low certainty of evidence. CONCLUSION: The findings show potential for better outcomes in the intervention; however, the evidence remains inconclusive highlighting a large research gap in ulcer treatment and warrant better-designed clinical trials. PROSPERO REGISTRATION NUMBER: CRD42022352418.

Investigating the sustainability of self-help programmes in the context of leprosy and the work of leprosy missions in Nigeria, Nepal and India: a qualitative study protocol.

INTRODUCTION: Leprosy occurs among very poor people who may be stigmatised and pushed further to the margins of society. Programmes to improve social integration and stimulate economic development have been implemented to help break the vicious cycle of poverty, reduced quality of life and ulcer recurrence. These involve forming groups of people, with a common concern, to provide mutual support and form saving syndicates-hence the term 'self-help groups' (SHGs). While there is literature on the existence and effectiveness of SHGs during the funded periods, little is known about their sustainability. We aim to explore the extent to which SHG programme activities have continued beyond the funding period and record evidence of sustained benefits. METHODS AND ANALYSIS: In India, Nepal and Nigeria, we identified programmes funded by international non-governmental organisations, primarily aimed at people affected by leprosy. In each case, financial and technical support was allocated for a predetermined period (up to 5 years).We will review documents, including project reports and meeting minutes, and conduct semistructured interviews with people involved in delivery of the SHG programme, potential beneficiaries and people in the wider environment who may have been familiar with the programme. These interviews will gauge participant and community perceptions of the programmes and barriers and facilitators to sustainability. Data will be analysed thematically and compared across four study sites. ETHICS AND DISSEMINATION: Approval was obtained from the University of Birmingham Biomedical and Scientific Research Ethics Committee. Local approval was obtained from: The Leprosy Mission Trust India Ethics Committee; Federal Capital Territory Health Research Ethics Committee in Nigeria and the Health Research Ethics Committee of Niger State Ministry of Health; University of Nigeria Teaching Hospital and the Nepal Health and Research Council. Results will be disseminated via peer-reviewed journals, conference presentations and community engagement events through the leprosy missions.

Mental health of hypertensive patients and its association with their blood pressure in a rural area of Kancheepuram District, Tamil Nadu.

Introduction: Chronic diseases, such as type 2 diabetes mellitus and hypertension, are often associated with psychiatric comorbidities such as anxiety, depression, and somatization. Approximately, one-fourth of the adults were diagnosed with hypertension, and the proportion will reach about one-third by 2025. The prevalence of hypertension throughout India is 29.8% and the burden of hypertension in a rural area of Tamil Nadu is 25.2%. The compliance of drug intake depends on the mental health of the patient and this study intends to take care of patients with chronic illnesses. This study is designed to assess the mental health of hypertensive patients and its association with their blood pressure. Materials and Methods: A cross-sectional descriptive study was conducted among hypertensive patients in the field practice of a tertiary care medical college in the Kancheepuram district for a period of 3 months using a semi-structured validated schedule after obtaining the informed consent. The depression anxiety stress scale (DASS) scale was used to assess the mental health of hypertensive patients. Data were analyzed using the Statistical Package for Social Sciences (SPSS) version 23.0. Results: Most hypertensive patients were found in the age group of 40 to 60 years. About 53.4% of hypertensive patients with normal blood pressure were suffering from depression. In addition, about 44.6% of pre-hypertensive patients and 44.6% of stage II hypertensive patients were found to have severe depression. Conclusion: Overall, pre-hypertensive patients were suffering from depression when compared to other hypertensive patients. Family history and tobacco and alcohol intake were other factors associated with depression in hypertensive patients.

Cross-ocean patterns and processes in fish biodiversity on coral reefs through the lens of eDNA metabarcoding.

Increasing speed and magnitude of global change threaten the world's biodiversity and particularly coral reef fishes. A better understanding of large-scale patterns and processes on coral reefs is essential to prevent fish biodiversity decline but it requires new monitoring approaches. Here, we use environmental DNA metabarcoding to reconstruct well-known patterns of fish biodiversity on coral reefs and uncover hidden patterns on these highly diverse and threatened ecosystems. We analysed 226 environmental DNA (eDNA) seawater samples from 100 stations in five tropical regions (Caribbean, Central and Southwest Pacific, Coral Triangle and Western Indian Ocean) and compared those to 2047 underwater visual censuses from the Reef Life Survey in 1224 stations. Environmental DNA reveals a higher (16%) fish biodiversity, with 2650 taxa, and 25% more families than underwater visual surveys. By identifying more pelagic, reef-associated and crypto-benthic species, eDNA offers a fresh view on assembly rules across spatial scales. Nevertheless, the reef life survey identified more species than eDNA in 47 shared families, which can be due to incomplete sequence assignment, possibly combined with incomplete detection in the environment, for some species. Combining eDNA metabarcoding and extensive visual census offers novel insights on the spatial organization of the richest marine ecosystems.

Comparative Assessment of Clinical and Quality of Life Outcomes in Mandibular Angle Fractures Treated with Standard and Three-Dimensional Mini-Plates.

Aims and Objectives: To undertake a multidimensional comparative assessment of the standard and three dimensional (3D) mini-plates in managing isolated mandibular angle fractures (MAFs). Patients and Methods: Thirty-six subjects were divided equally into two groups. Group A underwent fixation with a standard 2 mm miniplate, while group B with 2 mm 3D mini-plates. Evaluations were done preoperatively (T0), postoperatively at one week (T1), one month (T2) and three months (T3). Maximal inter-incisal mouth opening (MIO) and mean bite force (MBF) at the central incisors, right and left molars were calculated. Postoperative complications and Quality of life (QoL) outcomes were evaluated using the short form Oral Health Impact Profile (OHIP-14). Results: Mean operative time was almost similar for both groups. Although mean MIO improved significantly from T1 to T3 in both groups, intergroup comparison of MIO was not significant. The MBF values were significantly higher in group B on the right and left molars at T2 and T3. Although significant improvement in OHIP-14 scores was seen from T2 to T3 in both the groups, intergroup comparison of OHIP was not significant. Conclusion: 3D plates demonstrated similar clinical and QoL outcomes compared to the standard mini-plates.

An individual randomised efficacy trial of autologous blood products, leukocyte and platelet-rich fibrin (L-PRF), to promote ulcer healing in leprosy in Nepal: the TABLE trial protocol.

BACKGROUND: Leprosy is curable with multidrug therapy and treatment in the early stages can prevent disability. However, local nerve damage can lead to injury and consequently recurring and disfiguring ulcers. The aim of this study is to evaluate the treatment of leprosy ulcers using an autologous blood product; leukocyte and platelet-rich fibrin (L-PRF) to promote healing. METHODS: This is a single-centre study in the Anandaban Hospital, The Leprosy Mission Nepal, Kathmandu, Nepal. Consenting patients (n=130) will be individually randomised in a single-blinded, controlled trial. Participants will be 18 years of age or older, admitted to the hospital with a clean, dry and infection-free chronic foot ulcer between 2 and 20 cm2 in size. If the ulcer is infected, it will be treated before enrolment into the study. The intervention involves the application of leukocyte and platelet-rich fibrin (L-PRF) matrix on the ulcer beds during twice-weekly dressing changes. Controls receive usual care in the form of saline dressings only during their twice-weekly dressing changes. Primary outcomes are the rate of healing assessed using standardised photographs by observers blind to allocated treatment, and time to complete re-epithelialization. Follow-up is at 6 months from randomisation. DISCUSSION: This research will provide valuable information on the clinical and cost-effectiveness of L-PRF in the treatment of leprosy ulcers. An additional benefit is the evaluation of the effects of treatment on quality of life for people living with leprosy ulcers. The results will improve our understanding of the scalability of this treatment across low-income countries for ulcer healing in leprosy and potentially other conditions such as diabetic ulcers. TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN14933421 . Registered on 16 June 2020.

Comparative study of the anaesthetic efficacy of 4% articaine versus 2% lidocaine with adrenaline during extraction of mandibular molars using an inferior alveolar nerve blocking technique.

Various anaesthetic agents have been used in dentistry for the extraction of teeth. The most commonly used local anaesthetic agent is lidocaine hydrochloride. Recently, articaine hydrochloride came into existence because of its versatile properties and longer duration of action. Due to lack of study of effects of articaine on various systems, the present study is aimed to compare the anaesthetic efficacy of articaine and lidocaine with adrenaline during the extraction of mandibular molars. A total of 100 patients was randomly divided into two groups (50 each) and clinical variables such onset and duration of anaesthesia, blood pressure, oxygen saturation, pulse rate, and pain perception were recorded at different time intervals using a visual analogue scale. The statistical analysis was performed using SPSS version 22.0. Mean and standard deviations, frequency distribution analysis, and the chi squared test were performed to calculate variables and a p< 0.05 was considered significant. Statistically significant differences were obtained regarding mean time of onset of anaesthesia (p< 0.001), mean duration of the anaesthetic effect (p< 0.001), and pain perception for the articaine group. No significant results were obtained for blood pressure, oxygen saturation, or pulse rate. During the deposition of articaine, patients reported less pain than with lidocaine. Articaine hydrochloride helped to achieve increased anaesthetic success in dental applications over lidocaine hydrochloride in terms of fast time of onset, longer duration, and less pain, all of which were attributed to its greater diffusion properties.

Evaluation of a self-help intervention to promote the health and wellbeing of marginalised people including those living with leprosy in Nepal: a prospective, observational, cluster-based, cohort study with controls.

BACKGROUND: People affected by leprosy are at increased risk of ulcers from peripheral nerve damage. This in turn can lead to visible impairments, stigmatisation and economic marginalisation. Health care providers suggest that patients should be empowered to self-manage their condition to improve outcomes and reduce reliance on services. Self-care involves carrying out personal care tasks with the aim of preventing disabilities or preventing further deterioration. Self-help, on the other hand, addresses the wider psychological, social and economic implications of leprosy and incorporates, for example, skills training and microfinance schemes. The aim of this study, known as SHERPA (Self-Help Evaluation for lepRosy and other conditions in NePAl) is to evaluate a service intervention called Integrated Mobilization of People for Active Community Transformation (IMPACT) designed to encourage both self-care and self-help in marginalised people including those affected by leprosy. METHODS: A mixed-method evaluation study in Province 5, Nepal comprising two parts. First, a prospective, cluster-based, non-randomised controlled study to evaluate the effectiveness of self-help groups on ulcer metrics (people affected by leprosy only) and on four generic outcome measures (all participants) - generic health status, wellbeing, social integration and household economic performance. Second, a qualitative study to examine the implementation and fidelity of the intervention. IMPACT: This research will provide information on the effectiveness of combined self-help and self-care groups, on quality of life, social integration and economic wellbeing for people living with leprosy, disability or who are socially and economically marginalised in low- and middle- income countries.

Accumulation curves of environmental DNA sequences predict coastal fish diversity in the coral triangle.

Environmental DNA (eDNA) has the potential to provide more comprehensive biodiversity assessments, particularly for vertebrates in species-rich regions. However, this method requires the completeness of a reference database (i.e. a list of DNA sequences attached to each species), which is not currently achieved for many taxa and ecosystems. As an alternative, a range of operational taxonomic units (OTUs) can be extracted from eDNA metabarcoding. However, the extent to which the diversity of OTUs provided by a limited eDNA sampling effort can predict regional species diversity is unknown. Here, by modelling OTU accumulation curves of eDNA seawater samples across the Coral Triangle, we obtained an asymptote reaching 1531 fish OTUs, while 1611 fish species are recorded in the region. We also accurately predict (R² = 0.92) the distribution of species richness among fish families from OTU-based asymptotes. Thus, the multi-model framework of OTU accumulation curves extends the use of eDNA metabarcoding in ecology, biogeography and conservation.

Comparative Evaluation of the Embrasure Wire versus Arch Bar Maxillomandibular Fixation in the Management of Mandibular Fractures: Are Arch Bars Replaceable?

The aim of this prospective study was to appraise the role of embrasure wiring in the treatment of mandibular fractures over the arch bar as adjunctive techniques of maxillomandibular fixation (MMF). This study was conducted on 40 patients who were surgically treated for mandibular fractures with accessory use of MMF (embrasure: group A vs. arch bars: group B). All patients were evaluated for demographic data, etiology, and location of fracture. Characteristically, the complications, including wire injury, infection, and malocclusion, were recorded. The data were analyzed using Student's t -test and chi-square test as appropriate. Statistical significance was set at p < 0.05). In this study, data from 40 patients were included. In group A (embrasure wiring), time required for placement of MMF was significantly less than (7.85 ± 0.81 minutes) that in group B, and also there was less incidence of wire prick to the operator in group A than in group B ( p < 0.05). However, in terms of wire prick and malocclusion, no statistically significant difference was noted in groups A and B ( p > 0.05). Patient treated with embrasure wiring intermaxillary fixation had better outcomes especially in terms of time of placement and less incidence of wire prick injury when compared with arch bar.

Opening a Can of Worms: Leprosy Reactions and Complicit Soil-Transmitted Helminths.

BACKGROUND: >94% of new annual leprosy cases are diagnosed in populations co-endemic for soil-transmitted helminths (STH). STH can profoundly dysregulate host immune responses towards Th2 bias, which can be restored over time after deworming. We hypothesize that STH co-infection is associated with leprosy reaction (denoted as simply "reaction" herein) occurrence within a co-endemic population. METHODS: A cohort study was performed on a cohort of Nepalese leprosy patients across treatment and diagnostic classifications who were screened by routine fecal smear microscopy and multiplex quantitative PCR (qPCR) for Ascaris lumbricoides (Al), Strongyloides stercoralis (Ss), Ancyclostoma duodenale (Ad) and Necator americanus (Na). RESULTS: Among 145 patients, 55% were positive for ≥1 STH (STH+): 34% Al+, 18% Ss+, 17% Ad+and 5% Na+. Significant inverse STH and reaction relationships were evidenced by the bulk of cases: 63% reaction-negative were STH+ of total cases (p=0.030) while 65% reaction-positive were STH- in new cases (96; p=0.023). Strikingly, the majority of STH+ were reaction-negative, even when considering each species: 59% Al+, 60% Ss+, 62% Ad+and 67% Na+of new leprosy cases. CONCLUSIONS: Absence of STH co-infection is associated with leprosy reaction at diagnosis within a co-endemic population. This is likely due to immune reconstitution effects after deworming or interruption of chronic STH-mediated immune dysregulation.

Treatment of Mandibular Angle Fractures with Single Three-Dimensional Locking Miniplates without Maxillomandibular Fixation: How Much Fixation Is Required?

The aim of this simple nonrandomized and observational study was to evaluate the efficacy of single three-dimensional (3D) plate for the treatment of mandibular angle fractures without maxillomandibular fixation. A total of 30 patients with noncomminuted fractures of mandibular angle requiring open reduction and internal fixation were included in the study. All the patients were treated by open reduction and internal fixation using single 3D titanium locking miniplate placed with the help of transbuccal trocar or Synthes 90-degree hand piece and screw driver. 3D locking titanium miniplates used in our study was four-holed, box-shaped plate, and screws with 2 mm diameter and 8 mm length. The following clinical parameters were assessed for each patient at each follow-up visit: pain (visual analog scale: 0-5), swelling (visual analog scale: 0-5), mouth opening, infection, paresthesia, hardware failure (plate fracture), occlusal discrepancies, and mobility between fracture fragments. A significant decrease in pain level was seen during the follow-up visits. No statistically significant changes were seen in swelling, but mouth opening increased in the subsequent visits. Also better results were seen in terms of fracture stability and occlusion in the postoperative period. Two cases of infection and two cases of hardware failure were noted in sixth postoperative week. 3D plating system is an easy to use alternative to conventional miniplates to treat mandibular angle fractures that uses lesser foreign material, thus reducing the operative time and overall cost of the treatment. Better fracture stability and occlusion was also achieved using the 3D plating system.

Bite Force Evaluation of Conventional Plating System Versus Locking Plating System for Mandibular Fracture.

AIMS AND OBJECTIVES: To compare and evaluate the variation in recorded bite forces in patients with mandibular fractures undergoing open reduction and rigid internal fixation using standard 2.0 versus 2.0 mm locking miniplates. MATERIALS AND METHODS: A prospective randomized study was conducted for the treatment of mandibular fractures. Twenty adult patients with 31 mandibular fractures requiring an open reduction and internal fixation were included in the study. The sample was divided into two groups depending upon whether the patients received 2.0 mm non-locking (standard) or 2.0 mm locking miniplates for rigid fixation respectively. Bite force was evaluated at 1st, 3rd and 6th week after the open reduction and rigid fixation using miniplates. RESULTS: A statistically significant difference was not found in the clinical parameters such as pain, swelling, infection, paresthesia, hardware failure, and mobility between the fracture segments. The results showed that amongst locking vs non-locking miniplates, the former showed a greater bite force enhancement when compared to baseline values(post-trauma).A comparison between 2nd day post-operative vs 6th week post-operative values showed a significant increase in bite force in Group 1 (non-locking) (p < 0.05) whereas the values Were highly significant (p < 0.001) in Group 2 (locking Plate). CONCLUSION: The findings were suggestive that the efficacy of locking miniplates plate in mandibular fracture was superior in terms of bearing the masticatory loads during osteosynthesis of the fracture. However, the clinical results were almost similar to those seen with non-locking miniplate osteosynthesis.

Pre-emptive effect of dexamethasone injection and consumption on post-operative swelling, pain, and trismus after third molar surgery. A prospective, double blind and randomized study.

AIM: To evaluate the preventative effect of intravenous 4 mg of dexamethasone and 8 mg oral dexamethasone on post-operative pain, swelling and trismus after the surgical extraction of mandibular third molars. MATERIALS AND METHODS: A randomized clinical trial comprised of 200 patients (control group I intravenous and experimental group II orally) with impacted lower third molars, average age 20.8 years with no local or systemic problems, with bilateral impacted lower third molars, were operated under local anesthesia. Group I was given 4 mg IV and group II was given 8 mg orally of dexamethasone 1 h before procedure. The choice of which side to operate first and the amount of concentration of medication to use was made randomly and double-blindly. Post-operative pain was evaluated using a visual analog scale (VAS) and the degree of swelling was evaluated through facial reference points' variation. The presence of trismus was analyzed through measurement of the interincisal distance (IID). These assessments were obtained before the operation and 24 h, 48 h and 7th POD. RESULTS: No significant difference was found in facial swelling and trismus between IV 4 mg injection and oral 8 mg consumption after lower third molar surgery (student t test P > 0.05). The visual analogue scale scores for pain assessment showed no significant difference between IV injection and oral route of dexamethasone (student t test P > 0.05). CONCLUSION: Patients can be administered 8 mg oral dexamethasone is as effective as 4 mg intra venous route without much difference in final outcome at any given point of time.

Fracture of mandibular condyle­to open or not to open: an attempt to settle the controversy.

OBJECTIVE: To compare the outcome of the open method versus the closed method of treatment for mandibular condylar fracture. STUDY DESIGN: Fifty patients with fractures of the mandibular condylar processes were evaluated. All fractures were displaced, with a degree of deviation between the condylar fragment and the ascending ramus of 10 to 45 degrees (mediolaterally). The patients were randomly divided into two groups, with group 1 receiving open reduction internal fixation and group 2 receiving closed reduction. The follow-up was done over the period of 6 months. RESULTS: Statistically significant improvement was seen in group 1 compared with group 2 in terms of anatomic reduction of the condyle, shortening of the ascending ramus, occlusal status, and deviation on mouth opening. CONCLUSIONS: A statistically significant difference was seen in the patients treated with the open method, with improved temporomandibular joint functions and fewer short- and long-term complications compared with those treated with the closed method.

Acupuncture ( zhen jiǔ) - an emerging adjunct in routine oral care.

Acupuncture ( Zhen Jiǔ) ('acus' (needle) + 'punctura' (to puncture)) is the stimulation of specific points along the skin of the body involving various methods such as penetration by thin needles or the application of heat, pressure, or laser light. Acupuncture ( Zhen Jiǔ) aims to treat a range of medical and dental ailments, though is most commonly used for pain relief. This article reviews about the various possible roles of acupuncture ( Zhen Jiǔ) in clinical dental practice. Acupuncture ( Zhen Jiǔ) has potential in supplementing conventional treatment procedures by its diverse applicability outreach. Role of acupuncture ( Zhen Jiǔ) in dental practice has been well supported by clinical trials. Its role in alleviating facial pain, pre-operative and post-operative dental pain has led to its widespread application. Its role as sole analgesic for treatment procedure has to be tested. It's It is a thought that acupuncture ( Zhen Jiǔ) may prove an indispensible supplement to conventional treatment modalities and more of clinical trials and studies are required to prove the efficacy. Acupuncture ( Zhen Jiǔ) is not a miracle cure and is not going to replace the drill. However, the technique can be a supplement to conventional treatments in TMDs, facial pain, pain management Sjoegrens syndrome, and in phobias and anxiety. The application and use of Acupuncture ( Zhen Jiǔ) comes with some side effects. Proper training needs to be obtained before commencement of any procedure related to acupuncture ( Zhen Jiǔ). Various training programs are offered to train clinical practitioners the apt method to use acupuncture ( Zhen Jiǔ).

Pharmacological studies of geissoschizine methyl ether, isolated from Uncaria sinensis Oliv., in the central nervous system.

The pharmacological properties of geissoschizine methyl ether, isolated from Uncaria sinensis Oliv., were analyzed in vitro and in vivo using mice central serotonin neurons. In the in vitro experiment, geissoschizine methyl ether inhibited [3H]8-hydroxy-2-(di-n-propylamino)tetralin) ([3H]8-OH-DPAT) (K(i)=0.8 microM), [3H]mesulergine (K(i)=0.9 microM) and [3H]ketanserin (K(i)=1.4 microM), but had less affinity toward [3H]prazosin (K(i) > 10 microM) and [3H]spiperone (K(i) >15 microM) binding to mouse brain membranes. The in vivo studies showed that geissoschizine methyl ether dose-dependently reduced 5-hydroxy-L-tryptophan (I-5-HTP) plus clorgyline-induced head twitch response without inhibiting the I-5-HTP plus clorgyline and 8-OH-DPAT-induced head weaving. On the other hand, geissoschizine methyl ether also decreased the rectal temperature of mice (hypothermic response) in a dose-dependent manner. These results suggest that geissoschizine methyl ether possesses mixed 5-HT(1A) receptor agonist/5-HT(2A/2C) receptor antagonist activities and inhibits the head twitch response by blocking the 5-HT(2A) receptors, and possibly, at least in part, by stimulating the 5-HT(1A) receptors in the central nervous system.