Therapeutic Hotline. Oral allicin in the treatment of Behcet's disease through attenuating oxidative stress: A pilot study in 20 patients with mucocutaneous lesions.

Behçet's disease (BD) involves oxidative stress (OS) aggression and imbalanced oxidant/antioxidant status. Owing to its antioxidant property, allicin is proposed for treating BD. In this study, we aimed to investigate the efficacy and safety of allicin on patients with BD with mucocutaneous involvement. Twenty patients with active BD were treated with allicin for 12 weeks and followed up to 16 weeks. A clinical manifestations index and scoring system was the primary technique for efficacy evaluation at baseline and Week 4, 12, 16. The secondary efficacy variables were OS-related biomarkers determined at first and final visit. Side effects were assessed at each visit. By the end of study, 18 patients completed the trail. Allicin was effective in decreasing ulcer and cutaneous parameters (p < .05). Especially, the greatest reduction of mucocutaneous scores emerged from baseline after the first four-week treatment (p < .05). Meanwhile, allicin remarkably ameliorated OS-related parameters. Besides, some side effects were observed on allicin, these adverse reactions, however, disappeared upon cessation of drugs. In conclusion, allicin is a safe and effective treatment for BD, which may be associated with its inhibiting OS and regulating oxidant/antioxidant status balance.

The Role of Nerve Growth Factor (NGF) and Its Precursor Forms in Oral Wound Healing.

Nerve growth factor (NGF) and its different precursor forms are secreted into human saliva by salivary glands and are also produced by an array of cells in the tissues of the oral cavity. The major forms of NGF in human saliva are forms of pro-nerve growth factor (pro-NGF) and not mature NGF. The NGF receptors tropomyosin-related kinase A (TrkA) and p75 neurotrophin receptor (p75NTR) are widely expressed on cells in the soft tissues of the human oral cavity, including keratinocytes, endothelial cells, fibroblasts and leukocytes, and in ductal and acinar cells of all types of salivary glands. In vitro models show that NGF can contribute at most stages in the oral wound healing process: restitution, cell survival, apoptosis, cellular proliferation, inflammation, angiogenesis and tissue remodeling. NGF may therefore take part in the effective wound healing in the oral cavity that occurs with little scarring. As pro-NGF forms appear to be the major form of NGF in human saliva, efforts should be made to study its function, specifically in the process of wound healing. In addition, animal and clinical studies should be initiated to examine if topical application of pro-NGF or NGF can be a therapy for chronic oral ulcerations and wounds.

Proteomic and N-glycoproteomic quantification reveal aberrant changes in the human saliva of oral ulcer patients.

Human whole saliva is a vital body fluid for studying the physiology and pathology of the oral cavity. As a powerful technique for biomarker discovery, MS-based proteomic strategies have been introduced for saliva analysis and identified hundreds of proteins and N-glycosylation sites. However, there is still a lack of quantitative analysis, which is necessary for biomarker screening and biological research. In this study, we establish an integrated workflow by the combination of stable isotope dimethyl labeling, HILIC enrichment, and high resolution MS for both quantification of the global proteome and N-glycoproteome of human saliva from oral ulcer patients. With the help of advanced bioinformatics, we comprehensively studied oral ulcers at both protein and glycoprotein scales. Bioinformatics analyses revealed that starch digestion and protein degradation activities are inhibited while the immune response is promoted in oral ulcer saliva.

Photobiomodulation regulates cytokine release and new blood vessel formation during oral wound healing in rats.

The aim of the present study was to evaluate the effects of photobiomodulation (PBM) on cytokine levels and angiogenesis during oral wound healing. Ulcers were made on the dorsum of the tongue in 48 Wistar rats. Irradiation with an indium-gallium-aluminum-phosphide (InGaAlP) laser (660 nm; output power, 40 mW; spot size, 0.04 cm(2)) was performed once a day on two points of the ulcer for 14 days. Two different energy densities were used: 4 J/cm(2) (energy per point 0.16 J, total energy 0.32 J) and 20 J/cm(2) (energy per point 0.8 J, total energy 1.6 J). Tissue levels of interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were investigated by enzyme-linked immunosorbent assay (ELISA). Image analysis of CD31-immunostained sections was used to investigate microvessel density (MVD). PBM increased the tissue levels of IL-1ß at the early stage of oral wound healing (p < 0.01) and increased the tissue levels of TNF-α during all stages of oral wound healing (p < 0.05). PBM at a dose of 4 J/cm(2) produced more significant results regarding cytokine modulation and was associated with higher MVD at day 5. Collectively, these findings indicate that cytokine modulation and increased angiogenesis are among the basic mechanisms whereby PBM improves oral wound repair.

Differential expression of suppressor of cytokine signalling proteins in Behçet's disease.

Behçet's disease (BD) is a chronic, multisystemic, recurrent vasculitis disease of unknown aetiology. Proinflammatory cytokines are a key feature of the disease, but the triggers for their induction are not well understood and/or controversial. Suppressor of cytokine signalling (SOCS) proteins which negatively regulate the JAK-STAT signalling pathway of cytokine induction may be dysregulated in BD. The expression of SOCS1 and 3 mRNA and protein was studied in peripheral blood mononuclear cells (PBMCs) and neutrophils of patients with BD and compared with healthy controls (HCs) and patients with recurrent aphthous stomatitis (RAS) using RT-PCR, Western blot and immunohistochemistry. SOCS1 and 3 mRNA was also measured in buccal mucosal cells (BMC) of patients with BD and HCs. SOCS1 and 3 mRNA was significantly upregulated in PBMCs of patients with BD compared with HCs (P = 0.0149; P = 0.0007). In addition, there were subtle differences between expression in active and symptom-free BD (quiescent BD). SOCS1 and SOCS 3 were also significantly upregulated in BMC from oral ulcers of BD compared with HCs (both at P = 0.0001). A differential expression of both SOCS1 and 3 was observed between PBMCs and neutrophils in patients with BD. Immunohistochemical analysis revealed differential expression of SOCS proteins in the buccal mucosa with an increased expression at the ulcer surface of ulcers than in the non-ulcerated tissue. These observations suggest a dysregulation of the expression of these important regulators not only between patients with BD and healthy controls but also between mucosal and systemic tissues, which may reflect the nature of the aetiopathology of the disease.

Bioadhesive lipid compositions: self-assembly structures, functionality, and medical applications.

Lipid-based liquid crystalline compositions of phospholipids and diglycerides have unique bioadhesive properties with several medical applications, as exemplified by a lipid-based medical device indicated for management and relief of intraoral pain. The present paper describes the relation between self-assembly properties of phosphatidyl choline (PC) and glycerol dioleate (GDO) mixtures in the presence of aqueous fluids and functional attributes of the system, including: film formation and bioadhesion, intraoral coverage, acceptance by patients, and potential as a drug delivery system. The phase behavior of PC/GDO was characterized using synchrotron small-angle X-ray scattering. Functional properties, including the presence of study formulations at intraoral surfaces, ease of attachment, taste, and degree of and intraoral pain, were assessed in a crossover clinical pilot study in head and neck cancer patients. An optimum in functional properties was indicated for formulations with a PC/GDO weight ratio of about 35/65, where the lipids form a reversed cubic liquid crystalline micellar phase structure (Fd3m space group) over the relevant temperature range (25-40 °C).

Oxidative stress and recurrent aphthous stomatitis.

OBJECTIVES: This study analyzed the oxidative stress status in patients with recurrent aphthous stomatitis (RAS) in the presence and absence of active ulceration. MATERIAL AND METHODS: Oxidative stress was analyzed in peripheral mononuclear cells of 28 RAS patients with active ulceration and 29 controls. A further blood sample was collected from nine subjects randomly selected from the 28 RAS cases, during the period in which the patients did not have active oral ulceration. The reduced glutathione (GSH), malondialdehyde (MDA), and oxidized glutathione (GSSG) levels were measured in these samples. RESULTS: The mean MDA and GSSG levels were significantly higher in patients with active RAS than in the controls, while GSH was lower in the RAS group (p < 0.01). There was a nonsignificant tendency toward higher MDA and GSSG levels in patients with major RAS compared with minor RAS. On comparing the serum findings in the nine RAS patients in the presence and absence of lesions, the presence of ulceration was associated with even higher MDA and GSSG levels and lower GSH concentrations (p < 0.05) CONCLUSIONS: Oxidative stress was detected in our RAS patients.

[Antioxidant activity of Euryale ferox seed shell extract and its therapeutic effects on oral ulcer in rats].

OBJECTIVE: To investigate the therapeutic effect of Euryale ferox seed shell extract on oral ulcer in rats and its underlying mechanism. METHODS: The contents of polyphenols and flavonoids in Euryale ferox seed shells were determined by Folin-phenol assay and aluminum nitrate colorimetry, respectively. DPPH·, ABTS+·, ·OH and·O2- scavenging experiments were performed to evaluate the antioxidant activities of Euryale ferox seed shell extract in vitro. In a rat model of oral ulcer induced by burning with glacial acetic acid, the therapeutic effect of Euryale ferox seed shell extract was assessed by detecting changes in serum levels of oxidative factors by enzyme-linked immunosorbent assay (ELISA) and observing pathological changes of the ulcerous mucosa using HE staining; the therapeutic mechanism of the extract was explored by detecting the expression levels of Keap1, Nrf2, Nes-Nrf2 and HO-1 proteins in ulcerous mucosa using Western blotting. RESULTS: The ethyl acetate extract of Euryale ferox seed shells contained 306.74±1.04 mg/g polyphenols and 23.43±0.61 mg/g flavonoids and had IC50 values for scavenging DPPH· and ABTS+· free radicals of 3.42 ± 0.97 µg/mL and 3.32 ± 0.90 µg/mL, respectively. In the rat models, the ethyl acetate extract significantly ameliorated oral mucosal ulcer, increased serum CAT level, and decreased serum MDA level. The protein expression levels of Nes-Nrf2 and HO-1 were increased and Keap1 protein expression was lowered significantly in the ulcerous mucosa of the rats after treatment with the extract (P<0.05 or 0.01). CONCLUSION: The therapeutic effect of Euryale ferox seed shell extract on oral ulcers in rats is mediated probably by activation of the Keap1/Nrf2/HO-1 signaling pathway.

Effect of fenugreek oil on healing of experimentally induced buccal mucosal ulcer by immunohistochemical evaluation of Ki-67 expression.

Wound healing involves multiple populations of cells, the extracellular matrix, and soluble mediators' actions like growth factors and cytokines. Wound care was the target of many research, utilizing new therapy techniques and the progression of acute and chronic wound treatments with techniques involving plants to improve healing and decrease the side effects of drugs. When fenugreek is applied to an ulcer, its anti-inflammatory components are released, reducing unnecessary inflammation and accelerating the healing process. Healing is controlled by growth factors that naturally activate and boost the proliferation of cells, such as Ki-67, which is associated with the growth fraction and represents the cell's ability to proliferate. The current study aims to assess the expression of Ki-67 in rat mucosal ulcers treated with fenugreek leave oil. Twenty-four male Wistar albino rats of 350-450 gm weight were used. The rats were grouped as follows; normal group (normal tissue without ulcer induction), control group (tissue with surgical ulcer induction on the right side), and study group (ulcer treated with fenugreek leave oil on the left side), and had been sacrificed at 3- and 7-day healing durations. Thereafter, the tissue specimens were used for immunohistochemical analysis of Ki-67. The obtained outcomes showed that expression of Ki-67 increased in groups where ulcers were induced, with significant differences between control and study groups on the 3rd day. It was concluded that the application of fenugreek oil had an accelerating effect on the healing process of mucosal ulcers, as indicated by the elevated expression level of Ki-67.

Silk Fibroin Microneedles Loaded with Lipopolysaccharide-Pretreated Bone Marrow Mesenchymal Stem Cell-Derived Exosomes for Oral Ulcer Treatment.

Oral ulcers, superficial lesions on the surface of the oral mucosa, have a high incidence rate, and their main symptoms include local pain and erosion. Lipopolysaccharide (LPS)-preconditioned bone marrow mesenchymal stem cells and their secreted exosomes (LPS-pre-Exos) have been shown to promote recovery in various inflammatory conditions and wounds. However, studies documenting LPS-pre-Exos as a therapeutic intervention for oral mucosal-like diseases are lacking. In this study, we prepared a silk fibroin microneedle (MN) patch consisting of LPS-pre-Exos and zeolitic imidazolate framework-8 (ZIF-8) that localized at the tip and base, respectively, and used this MN patch for oral ulcer treatment. Upon insertion into the oral mucosa, continuous LPS-pre-Exos release was observed, which promoted macrophage polarization and tissue healing. Additionally, the ZIF-8 framework in the MN patch facilitated the controlled release of Zn2+, which demonstrated potent antimicrobial properties via synergistic effects. The in vitro experimental results showed that the silk fibroin MN patch can continuously release LPS-pre-Exos and Zn2+ for more than 7 days. Thus, the LPS-pre-Exos and ZIF-8-loaded silk fibroin MN patch exhibited good anti-inflammatory and antibacterial properties, promoting oral ulcer healing, and showed good histocompatibility. Hence, it may represent a potentially valuable strategy for facilitating oral ulcer healing.

The Correlation Between IFNG Gene Methylation and Th1|Th2 Cell Balance in ROU and the Interventional Study of Jiaweidaochi Powder.

The pathogenesis of recurrent oral ulcers (ROU) is complex, with a long duration of illness and challenging to cure. According to traditional Chinese medicine (TCM),"heat accumulation in the heart-spleen" is one of the main causative factors. Jiaweidaochi powder (JWDCP) is based on the ancient Chinese medicine formula JWDCS, with the addition of Tongcao and gypsum and the removal of Mu Tong. It is generally used to treat "heat accumulation in the heart-spleen." Previous studies have demonstrated that it effectively reduces recurrence rates and is anti-inflammatory in modulating immunity. The ROU rats' model for JWDCP intervention treatment had been established, and histological tests revealed that JWDCP has a therapeutic effect on the pathological changes in the oral mucosa. In addition, the methylation levels of peripheral blood IFNG gene were detected by bisulfite sequencing PCR (BSP), and the methylation levels of the IFNG promoter region in the model group and each dose group were lower than those in the control group. However, no significant methylation differences were observed. Furthermore, the results of enzyme-linked immunosorbent assay (ELISA) and RNA quantitative polymerase chain reaction showed that JWDCP could reduce IFN-γ and IL-4 protein concentrations, with high GATA-3 mRNA production, T-bet mRNAproduction was upgraded, elevated IL-4 mRNA levels, and reduced IFN-γ mRNA levels after treatment (P < 0.001). The expression of transcription factor T-betmRNA and GATA-3 gene mRNA was accompanied by changes in IFN-γmRNA and IL-4mRNA, demonstrating that Th2 type differentiation in RAS suppresses the body's immunity and that the imbalance of transcription factor expression further leads to Th1/Th2 drift. JWDCP is likely to reduce the protein concentration by regulating the imbalance of transcription factors and enhancing antioxidant capacity, thus achieving therapeutic effects. Treatment of recurrent oral ulcer models is not sufficient to reset IFNG methylation levels, correlating with the refractoriness of ROU, further confirming the complexity of epigenetic mechanisms and that epigenetic alterations in specific mediators may persist locally.

Eosinophilic ulcer of the oral mucosa.

A 56-year-old woman presented with a painless lesion on the inner aspect of her upper lip. The clinical differential diagnoses were oral syphilitic chancre, tuberculosis, histoplamosis, and neoplasia. A biopsy was performed, and the histopathologic diagnosis revealed an eosinophilic ulcer of the oral mucosa. Based on this case, we discuss the history, mechanisms of pathogenesis, clinical manifestations, histopathology, differential diagnosis, and therapy of eosinophilic ulcer of the oral mucosa.

Anti-inflammatory effect of HGF responses to oral traumatic ulcers using an HGF-Tg mouse model.

Hepatocyte growth factor (HGF) has been implicated in inhibiting diverse types of inflammation. Oral traumatic ulceration (OTU) is a common disease of the oral mucosa, and inflammation is the main process for ulcer healing. This study aimed to explore the expression of HGF in oral ulcers and its role in ulcer inflammation. The saliva of 14 recurrent alphous stomatitis (RAS) patients, 18 OTU patients and 17 healthy controls was collected. Traumatic ulcers of the left mucosa were observed in 42 wild-type (WT) and 42 HGF-overexpressing transgenic (HGF-Tg) mice. Histological scores, inflammatory cell expression and serum cytokine expression were measured and analyzed on the 5th day. The HGF protein level in ulcer-affected human saliva was 9.3-fold higher than that in healthy saliva. The HGF protein levels in RAS and OTU saliva were 14- and 5.7-fold higher, respectively, than those in healthy saliva. Traumatic ulcers enhanced HGF expression in ulcer-affected oral mucosa and in the blood of C57BL/6 mice by 1.21- and 1.40-fold, respectively. In HGF-Tg mouse traumatic ulcers, HGF expression was 1.34-fold higher than that in wild-type mice. HGF-Tg mice had lower weight loss, less ulcer area and lower histopathology scores than WT mice. The results from immunohistochemistry, flow cytometry and serum cytokine analysis showed that HGF-Tg animals presented fewer Ly6G-positive neutrophils and higher levels of circulating inflammatory cytokines. HGF overexpression alleviated weight loss, ulcer area and inflammation, suggesting the role of HGF in promoting the healing of oral ulcers.

Perforin and granzyme B involvement in oral lesions of lichen planus and chronic GVHD.

BACKGROUND: Oral lesions of lichen planus and chronic graft-vs.-host disease (cGVHD) have similar clinical and histological features, but distinct etiology. Apoptosis induced by cytotoxic T lymphocyte has been proposed as a mechanism of keratinocytes death. Cytotoxicity can be mediated by granules containing granzyme B and perforin. Since common features can reflect similarities in immunological mechanisms, we studied the role of those molecules in both diseases. METHODS: We analyzed 29 cases of oral lichen planus and 27 of oral cGVHD. The sections were studied on H&E, perforin and granzyme B staining. RESULTS: The total means (epithelium plus connective tissue number) of the granzyme B- and perforin-positive cells were significantly higher in cGVHD than in oral lichen planus lesions (P<0.05). Also, it was found that the higher the number of perforin+ cells, the higher the number of granzyme-B+ cells in the epithelium and in the connective tissue for both groups (P < 0.05). In oral lichen planus, the number of single apoptotic bodies had a positive correlation with connective tissue granzyme immunostaining and a negative correlation with perforin (P<0.01). On the contrary, in oral cGVHD, the number of apoptotic body clusters presented a positive correlation with connective tissue perforin (P<0.01). CONCLUSIONS: Our findings indicate that apoptosis in oral lichen planus seems to be correlated with granzyme B release, while in oral cGVHD, perforin seems to be more important. Although these diseases present clinical and histological similarities, subtle differences seem to exist in their pathogenetic mechanisms.

Comparative Evaluation of SMAD-2 Expression in Oral Submucous Fibrosis and Reactive Oral Lesions.

BACKGROUND: The event of fibrosis encompasses involvement of definite immunological and molecular mechanisms. As quite a lot of pro-fibrotic pathways are concerned, a multipronged approach is obligatory to cognize the fibrotic events. SMAD signaling pathway hasn't been studied oral fibrotic events.In the progression of cramming the SMAD signaling pathway in OSMF, the first initiator protein of the pathway was considered for evaluation in the present study. MATERIALS AND METHODS: A total of 100 subjects consisting of 20 controls, 40 patients with reactive lesions such as Traumatic Fibroma, Epulis Fissuratum and Gingival Hyperplasia and 40 patients with Oral Submucous Fibrosis were recruited for the study. Tissue homogenates were assayed by quantitative sandwich enzyme immunoassay technique using Human Mothers Against Decapentaplegic Homolog 2 (Smad2). RESULTS: SMAD 2 expression values showed significant difference between control and OSMF group. However, the difference between reactive lesions with control and OSMF were not statistically significant. CONCLUSION: Graded increase of SMAD 2 expression from control,reactive lesions and OSMF were observed accentuating the role of SMAD signalling pathway in fibro genesis. Further this can be validated to generate effective antifibrotic targets.

Abatacept treatment impairs the cell migration and wound healing of oral ulcers in rats: Role of interleukin (IL)-1ß, -6 and -10 and CD8/CD30 cells: Influence of abatacept treatment on oral wound healing: Experimental model on rats.

The present study aimed to evaluate the healing process of ulcers in the jugal mucosa of Wistar rats treated with abatacept. The rats were randomly assigned to four groups: saline-treated control (0.3 mL/kg) abatacept-treated groups at dosages of 3.2, 8.0 and 20.0 mg/kg/week. After two weeks of subcutaneous (SC) administration, ulcers were introduced into the left jugal mucosa with an 8-mm diameter punch. SC administration was continued until euthanasia (after 1, 3, 7, 14 and 21 days of ulceration), and ulcers were clinically measured and animals weighed. Histological slides were evaluated (healing scores and polymorphonuclear, mononuclear, vessel, and fibroblast/myofibroblast counts). We also performed collagenesis analysis (Picrosirius Red) and immunohistochemistry (induced nitric oxide synthase (iNOS), interleukin (IL)-1beta (1ß), -6, -10, plus the analysis of CD8 and CD30). The experiment was repeated to perform a vascular permeability assay. ANOVA 1-way or 2-way/Bonferroni and Kruskal-Wallis/Dunn tests were used for statistical analysis (GraphPad Prism 5.0®, p < 0.05). Abatacept treatment reduced the ulcer diameter and the numbers of polymorphonuclear and mononuclear cells; reduced the CD8+/CD30+ ratio and vascular permeability; and increased collagenesis and IL-10 expression at the beginning of the protocol. At the highest dose, there was a delay in repair and vascular proliferation; a reduction in the number of fibroblasts/myofibroblasts; and prolongation of iNOS, IL- and IL- expression. We conclude that abatacept accelerates the healing of oral ulcers by reducing the migration of inflammatory cells, but overdose of abatacept leads to delayed repair and prolongation of proinflammatory cytokine expression.

Evaluation of anti-inflammatory, analgesic and TNF-α inhibition (upon RAW 264.7 cell line) followed by the selection of extract (leaf and stem) with respect to potency to introduce anti-oral-ulcer model obtained from Olax psittacorum (Lam.) Vahl in addition to GC-MS illustration.

ETHNOPHARMACOLOGICAL RELEVANCE: Olax psittacorum (Lam.) Vahl., belongs to family olacaceae claimed as an "Issan folk medicine" portray the ethnomedicinal value like curative property of infection in the urinary tract, analgesic, antipyretic, skin-ulcer, antianemic (bark) as well as food additives (leaves). Research articles have proven the presence of anti-swelling property, laxative action, and antiviral activity against poliovirus moreover, the antioxidant property too. AIM OF THE EXPERIMENT: Evaluation of antiulcer property (induced within the oral mucosa) of the extract selected amongst two extracts based upon better property towards the ability of anti-inflammatory and analgesia through the in-vivo model as well as the inhibitory property of TNF-α (cell line RAW264.7). To justify the presence of activity extracts were introduced for GC-MS investigation. MATERIALS AND METHODS: Methanolic extracts (leaf; LME and stem; SME) were collected through maceration and introduced to carrageenan-induced paw edema to evaluate the anti-inflammatory activity and formalin-induced as well as tail-flick in-vivo models to evaluate the analgesic property. Anti-oral ulcer property was analyzed through the acetic-acid induced in-vivo model. The cytotoxicity was performed on mouse macrophages and fibroblast cells to find a toxic concentration of test substances and to evaluate their modulatory effect of TNF-α inhibition property against LPS induced toxicity. RESULTS: As compared to diclofenac (100 mg/kg) only LME and SME 200 mg/kg dose group have insignificant (P < 0.05) difference and P-values are 0.99 and 0.88 respectively. From the overall outcome, it can be concluded that compared to the diclofenac (100 mg/kg) group from 4th hours onwards LME (200 mg/kg) group was able to sustain the inflammation so similar. According to statistical consideration, LME (200 mg/kg) dose has also shown better results in formalin-induced analgesia as well as tail-flick. Cytotoxicity (CTC50) concentrations of LME and SME are 419.60 ± 4.09 and 230.21 ± 0.79 µg/ml respectively on RAW264.7 cell line. According to CTC50 the highest concentration of LME and SME is 400 and 200 µg/ml respectively has chosen to evaluate percentage inhibition of TNF-α as compared to diclofenac sodium (25 µg/ml). 50% inhibition was achieved by LME as well as diclofenac i.e. 51.2 ± 2.6% and 50.3 ± 0.8% instead of SME i.e. 45.2 ± 1.7%. As compared to the negative group on DAY-4, LME 200 mg/kg/bw dose shown proper growth of epithelial or mucosal layer which reveals proper healing of the surface of the tongue with no sign of injury. GC-MS results also reveal that, LME and SME both have Cyclohexasiloxane, dodecamethyl; Hexadecanoic acid, methyl ester which are responsible for anti-inflammatory and analgesic activity but besides, LME has more 4 compounds responsible for activities these are methyl salicylate; phytol; ß-Sitosterol; 9,12,15-Octadecatrienoic acid,2,3-bis[(trimethylsilyl)oxy]propyl ester, (Z, Z, Z). CONCLUSION: The overall outcomes of the study encapsulate that LME extract with a dose of 200 mg/kg/bw will be a good choice to overcome the above-cited ailments. Further studies upon this plant are needed to establish its importance in the human society through quantitative isolation of the metabolites and their pharmacokinetic as well as pharmacodynamic evaluation to establish the proper pathway of action.

Comparison of Salivary and Serum Alkaline Phosphates Level and Lactate Dehydrogenase Levels in Patients with Tobacco Related Oral Lesions with Healthy Subjects - A Step Towards Early Diagnosis.

AIM: To evaluate and compare salivary and serum levels of Alkaline Phosphates and Lactate Dehydrogenase in patients without the habit of tobacco, in patients with the habit of tobacco, in patients with benign oral lesions and in patients with oral premalignant lesions and oral malignant lesions. MATERIAL AND METHODOLOGY: This study was comprised of 500 subjects, Group I: 100 healthy individuals without the habit of tobacco usage formed the control group. Group II: 100 patients with the habit of tobacco/ smoking consumption without any oral lesion. Group III: 100 patients with benign oral lesions. Group IV: 100 patients having the history of tobacco consumption and having apparent precancerous lesions like leukoplakia, erythroplakia. Group V:100  patients having frank oral cancer. The grade of dysplasia in these patients was statically correlated with the levels of serum and salivary ALP and LDH. RESULTS: This study revealed that there was high expression of both serum and salivary ALP and LDH  in group IV and Group V as compared with the other groups and mean difference showed a statistically significant p value of less than 0.01. This study revealed that the in group V, the highest level of serum and salivary ALP was found in those patients who were reported with poorly differentiated oral cancer. CONCLUSION: Both Alkaline phosphates and Lactate dehydrogenase could be considered a sensitive markers for the detection of dysplasia with already existing precancancerous and cancerous lesions.