Human CYP2C19 Substrate and Inhibitor Characterization of Organophosphate Pesticides.

CYP2C19 is an important enzyme for organophosphate pesticide (OPP) metabolism. Because the OPPs can be both substrates and inhibitors of CYP2C19, we screened 45 OPPs for their ability to inhibit the activity of this enzyme and investigated the role of CYP2C19 in the metabolism of 22 of these molecules. We identified several nanomolar inhibitors of CYP2C19 as well as determined that thions, in general, are more potent inhibitors than oxons. We also determined that thions are readily metabolized by CYP2C19, although we saw no relationship between IC50 values and intrinsic clearance rates. This study may have implications for mitigating the risk of OPP poisoning.

Targeted Metabolomics of Organophosphate Pesticides and Chemical Warfare Nerve Agent Simulants Using High- and Low-Dose Exposure in Human Liver Microsomes.

Our current understanding of organophosphorus agent (pesticides and chemical warfare nerve agents) metabolism in humans is limited to the general transformation by cytochrome P450 enzymes and, to some extent, by esterases and paraoxonases. The role of compound concentrations on the rate of clearance is not well established and is further explored in the current study. We discuss the metabolism of 56 diverse organophosphorus compounds (both pesticides and chemical warfare nerve agent simulants), many of which were explored at two variable dose regimens (high and low), determining their clearance rates (Clint) in human liver microsomes. For compounds that were soluble at high concentrations, 1D-NMR, 31P, and MRM LC-MS/MS were used to calculate the Clint and the identity of certain metabolites. The determined Clint rates ranged from 0.001 to 2245.52 µL/min/mg of protein in the lower dose regimen and from 0.002 to 98.57 µL/min/mg of protein in the high dose regimen. Though direct equivalency between the two regimens was absent, we observed (1) both mono- and bi-phasic metabolism of the OPs and simulants in the microsomes. Compounds such as aspon and formothion exhibited biphasic decay at both high and low doses, suggesting either the involvement of multiple enzymes with different KM or substrate/metabolite effects on the metabolism. (2) A second observation was that while some compounds, such as dibrom and merphos, demonstrated a biphasic decay curve at the lower concentrations, they exhibited only monophasic metabolism at the higher concentration, likely indicative of saturation of some metabolic enzymes. (3) Isomeric differences in metabolism (between Z- and E- isomers) were also observed. (4) Lastly, structural comparisons using examples of the oxon group over the original phosphorothioate OP are also discussed, along with the identification of some metabolites. This study provides initial data for the development of in silico metabolism models for OPs with broad applications.

Impact of low-molecular-weight heparin in the treatment of moderately severe and severe acute pancreatitis; a randomized, single blind, phase 3 control trial.

INTRODUCTION: Acute pancreatitis is inflammation of pancreatic parenchyma which is an emergency condition. It is classified as mild, moderately severe, and severe categories. In severe acute pancreatitis, mortality is up to 10%-30%. Pancreatic abscess increases the mortality to 40%, and infected pancreatitis carries 100% mortality without surgical drainage. Anti-coagulant, anti-inflammatory and anti-protease activities of low-molecular-weight heparin are involved in preventing pancreatic necrosis and curbing the adverse outcomes of acute pancreatitis. AIM: To determine the effect of low-molecular-weight heparin on the outcome of moderately severe and severe acute pancreatitis. MATERIALS AND METHODOLOGY: Hospital based, single centre, randomized, single blind, phase 3 control trial. First 140 patients with moderately severe and severe acute pancreatitis admitted in hospital in the given period who met the inclusion and exclusion criteria were taken. 70 patients were placed in the control and the trial group each by simple randomization (closed envelope method). The control group received conventional treatment for pancreatitis & the trial group received 1mg/kg body weight Enoxaperin, subcutaneously, 12 hourly for seven days along with the conventional treatment. Progression of disease in Computed Tomography Severity Index and incidence of pancreatic necrosis were the main outcomes studied at the end of 7 days of treatment. RESULTS: 1386 acute abdomen cases were screened, of which 269 were diagnosed with acute pancreatitis. 147 patients with acute pancreatitis met the selection criteria and 7 were dropouts. Recruitment started on April 9, 2021 and closed on December 5, 2021. Computed Tomography Severity Index progressed in 22(31.40%) patients in control group and 6(8.6%) patients in the trial group and 18(25.71%) in the control group and 4(5.71%) in the trial group showed the presence of necrosis. The differences are significant (P value is 0.001 in each). No adverse events were seen. CONCLUSION: Use of low-molecular-weight heparin in early stage of moderately severe and severe acute pancreatitis significantly reduces the chance of disease progression and pancreatic necrosis.

Primary Angiosarcoma of Humerus - A Case Report and Literature Review.

INTRODUCTION: Osseous angiosarcoma is a very rare tumor of bone with aggressive behavior, propensity for recurrences, and distant metastasis. The etiology of osseous angiosarcoma is uncertain; however, specific risk factors have been recognized. The diagnosis of angiosarcoma of bone demands multimodality imaging in conjunction with histopathological and vascular marker evaluation to aptly differentiate them from other vascular tumors. Treatment of osseous angiosarcoma remains controversial. CASE REPORT: A 53-year-old male presented with pain and swelling of the right upper 1/3rd of the arm following heaviness while lifting weight for 3 months. He had a history of significant weight loss and appetite with no history of inciting trauma or irradiation in the past. On examination, a diffuse swelling was noted in the right shoulder and right scapular aspect with varied consistency and ill-defined borders and margins. The skin over the swelling was stretched and shiny with dilated engorged veins over it. The plain radiograph of the right shoulder with humerus revealed a large expansile lytic soft-tissue mass in the right proximal humerus with a wide zone of transition without sclerotic margins. Magnetic resonance imaging showed T1 hypointense, T2/PDFS hyperintense large well-defined expansile lytic lesion with multi-loculated cysts, and multiple blood-fluid levels involving right proximal humerus. The patient underwent an incisional biopsy which exhibited angiosarcoma of the humerus. The patient was treated with six cycles of chemotherapy with a mesna, doxorubicin, ifosfamide, and dacarbazine regimen. The patient was still under follow-up. CONCLUSION: Being a rare clinical entity, controversy exists in angiosarcoma of humerus regarding its etiology and recommended management protocols. Histopathology and immunohistochemistry remain the gold standard in differentiating osseous angiosarcoma from other osseous vascular tumors. The treatment protocol has to be standardized to decrease morbidity and to improve the functional quality of life of the patient.

Epidemiology, clinical profile, management, and outcome of COVID-19-associated rhino-orbital-cerebral mucormycosis in 2826 patients in India - Collaborative OPAI-IJO Study on Mucormycosis in COVID-19 (COSMIC), Report 1.

Purpose: COVID-19-associated rhino-orbital-cerebral mucormycosis (ROCM) has reached epidemic proportion during India's second wave of COVID-19 pandemic, with several risk factors being implicated in its pathogenesis. This study aimed to determine the patient demographics, risk factors including comorbidities, and medications used to treat COVID-19, presenting symptoms and signs, and the outcome of management. Methods: This was a retrospective, observational study of patients with COVID-19-associated ROCM managed or co-managed by ophthalmologists in India from January 1, 2020 to May 26, 2021. Results: Of the 2826 patients, the states of Gujarat (22%) and Maharashtra (21%) reported the highest number of ROCM. The mean age of patients was 51.9 years with a male preponderance (71%). While 57% of the patients needed oxygen support for COVID-19 infection, 87% of the patients were treated with corticosteroids, (21% for > 10 days). Diabetes mellitus (DM) was present in 78% of all patients. Most of the cases showed onset of symptoms of ROCM between day 10 and day 15 from the diagnosis of COVID-19, 56% developed within 14 days after COVID-19 diagnosis, while 44% had delayed onset beyond 14 days. Orbit was involved in 72% of patients, with stage 3c forming the bulk (27%). Overall treatment included intravenous amphotericin B in 73%, functional endoscopic sinus surgery (FESS)/paranasal sinus (PNS) debridement in 56%, orbital exenteration in 15%, and both FESS/PNS debridement and orbital exenteration in 17%. Intraorbital injection of amphotericin B was administered in 22%. At final follow-up, mortality was 14%. Disease stage >3b had poorer prognosis. Paranasal sinus debridement and orbital exenteration reduced the mortality rate from 52% to 39% in patients with stage 4 disease with intracranial extension (p < 0.05). Conclusion: : Corticosteroids and DM are the most important predisposing factors in the development of COVID-19-associated ROCM. COVID-19 patients must be followed up beyond recovery. Awareness of red flag symptoms and signs, high index of clinical suspicion, prompt diagnosis, and early initiation of treatment with amphotericin B, aggressive surgical debridement of the PNS, and orbital exenteration, where indicated, are essential for successful outcome.

Update on Phytochemical and Biological Studies on Rocaglate Derivatives from Aglaia Species.

With about 120 species, Aglaia is one of the largest genera of the plant family Meliaceae (the mahogany plants). It is native to the tropical rainforests of the Indo-Australian region, ranging from India and Sri Lanka eastward to Polynesia and Micronesia. Various Aglaia species have been investigated since the 1960s for their phytochemical constituents and biological properties, with the cyclopenta[b]benzofurans (rocaglates or flavaglines) being of particular interest. Phytochemists, medicinal chemists, and biologists have conducted extensive research in establishing these secondary metabolites as potential lead compounds with antineoplastic and antiviral effects, among others. The varied biological properties of rocaglates can be attributed to their unusual structures and their ability to act as inhibitors of the eukaryotic translation initiation factor 4A (eIF4A), affecting protein translation. The present review provides an update on the recently reported phytochemical constituents of Aglaia species, focusing on rocaglate derivatives. Furthermore, laboratory work performed on investigating the biological activities of these chemical constituents is also covered.

Masson's Hemangioma of Knee: A Rare Case Report.

INTRODUCTION: Intrasynovial hemangioma, a rare benign vascular lesion of joint cavities, is also called intrasynovial papillary endothelial hyperplasia or Masson's hemangioma (MH). These lesions are characterized by abnormal proliferation of endothelial cells with mild atypia with an organized thrombus. MH follows an individualized protocol for its management. CASE REPORT: A 22-year-old male gave a 10-year history of the diagnosed and operated (arthroscopically) case of synovial hemangioma of the left knee and presented with similar complaints. There was no history of trauma or infection over the left knee. The movements of the left knee were normal except with terminal restriction of movements. MRI of the left knee suggested intrasynovial low flow vascular malformation within the substance of the synovium. The patient underwent synovectomy of the hemangiomatous lesion in toto without any recurrence in the follow-up period for 8 months. Histopathology confirmed the diagnosis of intravascular papillary endothelial hyperplasia/MH. CONCLUSION: Although intrasynovial hemangioma is a very rare clinical entity, Orthopedic surgeons should have a high index of suspicion for MH, when a long-standing pain and hemarthrosis of the knee joint is being encountered in the clinical practice.

Hemangioma of First Extensor Compartment of the Wrist- A Rare Case Report.

Introduction: Although upper extremity intramuscular hemangioma is a rare clinical entity, it poses considerable morbidity in the functional needs of an individual. The diagnosis of intramuscular hemangioma poses a diagnostic glitch. The combined radiological and histopathological assessment provides a complete understanding and diagnosis for the same. Every tumor follows an individualized protocol for its management. Case Report: A 15-year-old female presented with swelling over dorsal aspect of distal 1/3rd right forearm, which was 3 cm away from the articular surface of the right wrist from the past 5 years. There was no history of trauma or infection over the right wrist. Finkelstein's test was negative, which rule out de Quervain's tenosynovitis. The movements of the right wrist were unrestricted without any distal neurovascular deficit. MRI of her right wrist and hand suggested the presence of low flow vascular malformation within the musculotendinous junction of APL and EPB muscles. The patient underwent excision biopsy of the hemangiomatous lesion in toto without any neurological complications. No recurrence was noted in the follow-up period for 6 months. Conclusion: Being a benign vascular tumor, MRI provides the gateway to diagnose intramuscular hemangioma for early intervention to provide better functional results. The choice of definitive treatment for APL and EPB hemangioma was excision biopsy in toto which provided better functional results in our patient.

Identification of Peptide Binders to Truncated Recombinant Chikungunya Virus Envelope Protein 2 Using Phage Display Technology and Their In Silico Characterization.

AIM: To identify and characterize peptide binders to truncated recombinant chikungunya virus envelope protein 2. BACKGROUND: Despite extensive research on the chikungunya virus (CHIKV), the specific antiviral treatment's unavailability has stressed the need for the urgent development of therapeutics. The Envelope protein 2 (E2) of CHIKV that displays putative receptor binding sites and specific epitopes for virus neutralizing antibodies is a critical target for the therapeutic intervention. OBJECTIVE: The study aims to identify the unique peptides that can bind to truncated E2 protein of CHIKV and further explore their properties as potential therapeutic candidate. METHODS: A stretch of CHIKV-E2 (rE2), which is prominently exposed on the surface of virion, was used as bait protein to identify peptide binders to the CHIKV-rE2 using a 12-mer phage display peptide library. Three rounds of biopanning yielded several peptide binders to CHIKV-rE2 and their binding affinities were compared by phage ELISA. Additionally, a fully flexible-blind docking simulation investigated the possible binding modes of the selected peptides. Furthermore, the selected peptides were characterized and their ADMET properties were explored in silico. RESULTS: Five peptides were identified as potential binders based on their robust reactivity to the bait protein. The selected peptides appeared to interact with the crucial residues that were notably exposed on the surface of E1-E2 trimeric structure. The explored in silico studies suggested their non-allergenicity, non-toxicity and likeliness to be antiviral. CONCLUSION: The potential binding peptides of CHIKV-rE2 protein were identified using phage display technology and characterized in silico. The selected peptides could be further used for the development of therapeutics against the CHIKV infection.>.

Antiviral Peptides: Identification and Validation.

Despite rapid advances in the human healthcare, the infection caused by certain viruses results in high morbidity and mortality accentuate the importance for development of new antivirals. The existing antiviral drugs are limited, due to their inadequate response, increased rate of resistance and several adverse side effects. Therefore, one of the newly emerging field "peptide-based therapeutics" against viruses is being explored and seems promising. Over the last few years, a lot of scientific effort has been made for the identification of novel and potential peptide-based therapeutics using various advanced technologies. Consequently, there are more than 60 approved peptide drugs available for sale in the market of United States, Europe, Japan, and some Asian countries. Moreover, the number of peptide drugs undergoing the clinical trials is rising gradually year by year. The peptide-based antiviral therapeutics have been approved for the Human immunodeficiency virus (HIV), Influenza virus and Hepatitis virus (B and C). This review enlightens the various peptide sources and the different approaches that have contributed to the search of potential antiviral peptides. These include computational approaches, natural and biological sources (library based high throughput screening) for the identification of lead peptide molecules against their target. Further the applications of few advanced techniques based on combinatorial chemistry and molecular biology have been illustrated to measure the binding parameters such as affinity and kinetics of the screened interacting partners. The employment of these advanced techniques can contribute to investigate antiviral peptide therapeutics for emerging infections.

Susceptibility to high-altitude pulmonary edema is associated with circulating miRNA levels under hypobaric hypoxia conditions.

Hypobaric hypoxia poses stress to sojourners traveling to high-altitude. A cascade of physiological changes occurs to cope with or adapt to hypobaric hypoxia. However, an insufficient physiological response to the hypoxic condition resulting from imbalanced vascular homeostasis pathways results in high-altitude pulmonary edema (HAPE). The present study aims to identify the implication of miRNAs associating with HAPE and adaptation. We analyzed the expression of 1,113 miRNAs in HAPE-patients (HAPE-p), HAPE-free controls (HAPE-f), and highland natives (HLs). Based on miRNA profiling and in silico analyses, miR-124-3p emerged relevantly. We observed a significant overexpression of miR-124-3p in HAPE-p. In silico analyses revealed a direct interaction of miR-124-3p with vascular homeostasis and hypoxia-associated genes NOS3 (endothelial nitric oxide synthase), Apelin, and ETS1 (V-Ets avian erythroblastosis virus E2 oncogene homolog 1). Moreover, the transcript and biolevel expression of these genes were significantly decreased in HAPE-p when compared with HAPE-f or HLs. Our in vitro analysis in human umbilical vein endothelial cells demonstrated a significant knockdown of these genes both at transcript and protein levels following miR-124-3p overexpression. Conclusively, our results showed that miR-124-3p might play a plausible role in HAPE pathophysiology by inhibiting the expression of NOS3, Apelin, and ETS1.

Current status and contemporary approaches to the discovery of antitumor agents from higher plants.

Higher plant constituents have afforded clinically available anticancer drugs. These include both chemically unmodified small molecules and their synthetic derivatives currently used or those in clinical trials as antineoplastic agents, and an updated summary is provided. In addition, botanical dietary supplements, exemplified by mangosteen and noni constituents, are also covered as potential cancer chemotherapeutic agents. Approaches to metabolite purification, rapid dereplication, and biological evaluation including analytical hyphenated techniques, molecular networking, and advanced cellular and animal models are discussed. Further, enhanced and targeted drug delivery systems for phytochemicals, including micelles, nanoparticles and antibody drug conjugates (ADCs) are described herein.

Targeting Protein Translation by Rocaglamide and Didesmethylrocaglamide to Treat MPNST and Other Sarcomas.

Malignant peripheral nerve sheath tumors (MPNST) frequently overexpress eukaryotic initiation factor 4F components, and the eIF4A inhibitor silvestrol potently suppresses MPNST growth. However, silvestrol has suboptimal drug-like properties, including a bulky structure, poor oral bioavailability (<2%), sensitivity to MDR1 efflux, and pulmonary toxicity in dogs. We compared ten silvestrol-related rocaglates lacking the dioxanyl ring and found that didesmethylrocaglamide (DDR) and rocaglamide (Roc) had growth-inhibitory activity comparable with silvestrol. Structure-activity relationship analysis revealed that the dioxanyl ring present in silvestrol was dispensable for, but may enhance, cytotoxicity. Both DDR and Roc arrested MPNST cells at G2-M, increased the sub-G1 population, induced cleavage of caspases and PARP, and elevated the levels of the DNA-damage response marker γH2A.X, while decreasing the expression of AKT and ERK1/2, consistent with translation inhibition. Unlike silvestrol, DDR and Roc were not sensitive to MDR1 inhibition. Pharmacokinetic analysis confirmed that Roc had 50% oral bioavailability. Importantly, Roc, when administered intraperitoneally or orally, showed potent antitumor effects in an orthotopic MPNST mouse model and did not induce pulmonary toxicity in dogs as found with silvestrol. Treated tumors displayed degenerative changes and had more cleaved caspase-3-positive cells, indicative of increased apoptosis. Furthermore, Roc effectively suppressed the growth of osteosarcoma, Ewing sarcoma, and rhabdomyosarcoma cells and patient-derived xenografts. Both Roc- and DDR-treated sarcoma cells showed decreased levels of multiple oncogenic kinases, including insulin-like growth factor-1 receptor. The more favorable drug-like properties of DDR and Roc and the potent antitumor activity of Roc suggest that these rocaglamides could become viable treatments for MPNST and other sarcomas.

Structurally Modified Cyclopenta[b]benzofuran Analogues Isolated from Aglaia perviridis.

Four new cyclopenta[b]benzofuran derivatives based on an unprecedented carbon skeleton (1-4), with a dihydrofuran ring fused to dioxanyl and aryl rings, along with a new structural analogue (5) of 5‴-episilvestrol (episilvestrol, 7), were isolated from an aqueous extract of a large-scale re-collection of the roots of Aglaia perviridis collected in Vietnam. Compound 5 demonstrated mutarotation in solution due to the presence of a hydroxy group at C-2‴, leading to the isolation of a racemic mixture, despite being purified on a chiral-phase HPLC column. Silvestrol (6) and episilvestrol (7) were isolated from the most potently cytotoxic chloroform subfraction of the roots. All new structures were elucidated using 1D and 2D NMR, HRESIMS, IR, UV, and ECD spectroscopic data. Of the five newly isolated compounds, only compound 5 exhibited cytotoxic activity against a human colon cancer (HT-29) and human prostate cancer cell line (PC-3), with IC50 values of 2.3 µM in both cases. The isolated compounds (1-5) double the number of dioxanyl ring-containing rocaglate analogues reported to date from Aglaia species and present additional information on the structural requirements for cancer cell line cytotoxicity within this compound class.

Lipid Membranes Influence the Ability of Small Molecules To Inhibit Huntingtin Fibrillization.

Several diseases, including Alzheimer's disease, Parkinson's disease, and Huntington's disease (HD), are associated with specific proteins aggregating and depositing within tissues and/or cellular compartments. The aggregation of these proteins is characterized by the formation of extended, ß-sheet rich fibrils, termed amyloid. In addition, a variety of other aggregate species also form, including oligomers and protofibrils. Specifically, HD is caused by the aggregation of the huntingtin (htt) protein that contains an expanded polyglutamine domain. Due to the link between protein aggregation and disease, small molecule aggregation inhibitors have been pursued as potential therapeutic agents. Two such small molecules are epigallocatechin 3-gallate (EGCG) and curcumin, both of which inhibit the fibril formation of several amyloid-forming proteins. However, amyloid formation is a complex process that is strongly influenced by the protein's environment, leading to distinct aggregation pathways. Thus, changes in the protein's environment may alter the effectiveness of aggregation inhibitors. A well-known modulator of amyloid formation is lipid membranes. Here, we investigated if the presence of lipid vesicles altered the ability of EGCG or curcumin to modulate htt aggregation and influence the interaction of htt with lipid membranes. The presence of 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine or total brain lipid extract vesicles prevented the curcumin from inhibiting htt fibril formation. In contrast, EGCG's inhibition of htt fibril formation persisted in the presence of lipids. Collectively, these results highlight the complexity of htt aggregation and demonstrate that the presence of lipid membranes is a key modifier of the ability of small molecules to inhibit htt fibril formation.

Biosynthesis of Hyaluronic acid polymer: Dissecting the role of sub structural elements of hyaluronan synthase.

Hyaluronic acid (HA) based biomaterials have several biomedical applications. HA biosynthesis is catalysed by hyaluronan synthase (HAS). The unavailability of 3-D structure of HAS and gaps in molecular understanding of HA biosynthesis process pose challenges in rational engineering of HAS to control HA molecular weight and titer. Using in-silico approaches integrated with mutation studies, we define a dictionary of sub-structural elements (SSE) of the Class I Streptococcal HAS (SeHAS) to guide rational engineering. Our study identifies 9 SSE in HAS and elucidates their role in substrate and polymer binding and polymer biosynthesis. Molecular modelling and docking assessment indicate a single binding site for two UDP-substrates implying conformationally-driven alternating substrate specificities for this class of enzymes. This is the first report hypothesizing the involvement of sites from SSE5 in polymer binding. Mutation at these sites influence HA production, indicating a tight coupling of polymer binding and synthase functions. Mutation studies show dispensable role of Lys-139 in substrate binding and a key role of Gln-248 and Thr-283 in HA biosynthesis. Based on the functional architecture in SeHAS, we propose a plausible three-step polymer extension model from its reducing end. Together, these results open new avenues for rational engineering of Class I HAS to study and regulate its functional properties and enhanced understanding of glycosyltransferases and processive enzymes.

Virtual screening of inhibitors against Envelope glycoprotein of Chikungunya Virus: a drug repositioning approach.

Chikungunya virus (CHIKV) a re-emerging mosquito-borne alpha virus causes significant distress which is further accentuated in the lack of specific therapeutics or a preventive vaccine, mandating accelerated research for anti-CHIKV therapeutics. In recent years, drug repositioning has gained recognition for the curative interventions for its cost and time efficacy. CHIKV envelope proteins are considered to be the promising targets for drug discovery because of their essential role in viral attachment and entry in the host cells. In the current study, we propose structure-based virtual screening of drug molecule on the crystal structure of mature Chikungunya envelope protein (PDB 3N41) using a library of FDA approved drug molecules. Several cephalosporin drugs docked successfully within two binding sites prepared at E1-E2 interface of CHIKV envelop protein complex with significantly low binding energies. Cefmenoxime, ceforanide, cefotetan, cefonicid sodium and cefpiramide were identified as top leads with a cumulative score of -67.67, -64.90, -63.78, -61.99, and - 61.77, forming electrostatic, hydrogen and hydrophobic bonds within both the binding sites. These shortlisted leads could be potential inhibitors of E1-E2 hetero dimer in CHIKV, hence might disrupt the integrity of envelope glycoprotein leading to loss of its ability to form mature viral particles and gain entry into the host.

Chondroid Tenosynovial Giant Cell Tumor of Temporomandibular Joint.

Tenosynovial giant cell tumor (TGCT), a benign proliferative lesion arising from the synovial membrane of the joints, is rarely seen in the temporomandibular joint. It frequently presents as a painful, preauricular swelling and affects the jaw functions. Two types of TGCT seen are diffuse TGCT (TGCT-D) and localized TGCT. A case of TGCT-D is described here, the highlight of the case being extensive areas of chondroid metaplasia which mimicked chondroid lesions, but was ruled out based on negative immunohistochemical findings within the tumor cells.

Comparative evaluation of pressure generated on a simulated maxillary oral analog by impression materials in custom trays of different spacer designs: An in vitro study.

INTRODUCTION: Literature reveals that masticatory load on denture bearing tissues through complete dentures should be maximum on primary stress bearing areas and least on relief area in accordance with the histology of underlying tissues. A study to validate the existing beliefs was planned to compare the pressure on mucosa using selective pressure technique and minimal pressure technique, with the incorporation of two different impression materials utilizing the pressure sensors during secondary impression procedure. MATERIALS AND METHODS: The study was performed using a maxillary analog. Three pressure sensors were imbedded in the oral analog, one in the mid palatine area and the other two in the right and left ridge crest. Custom trays of two different configurations were fabricated. The two impression materials tested were light body and zinc oxide eugenol. A total of 40 impressions were made. A constant weight of 1 kg was placed, and the pressure was recorded as initial and end pressures. RESULTS: A significant difference in the pressure produced using different impression materials was found (P < 0.001). Light body vinyl polysiloxane produced significantly lesser pressure than zinc oxide eugenol impression materials. The presence of relief did affect the magnitude of pressure at various locations. CONCLUSION: All impression materials produced pressure during maxillary edentulous impression making. Tray modification is an important factor in changing the amount of pressure produced. The impression materials used also had a significant role to play on the pressures acting on the tissues during impression procedure. CLINICAL IMPLICATION: Light body VPS impression material may be recommended to achieve minimal pressure on the denture bearing tissues in both selective as well as minimal pressure techniques.

Plasma Cell Neoplasm Manifesting Initially as a Sub-Cutaneous Supra-Orbital Swelling.

Multiple myeloma is a plasma cell neoplasm seen usually in patients over 50 years of age. Some cases may be asymptomatic initially and are detected during a routine test like complete blood count. They only require a close follow-up and monitoring. However, around 1% of these monoclonal gammopathy of undetermined significance progress to multiple myeloma every year and then they need to be taken care of by chemotherapy, targeted therapy, bisphosphonates and 6 monthly urine and bone examinations. Here, we present a case of 35-year-old female with an initial symptom of a vague backache along with a left subcutaneous supra-orbital swelling which was diagnosed as multiple myeloma by aspiration cytology and confirmed by ancillary tests. She has since been on treatment with bortezomib and prednisone and is responding well.