Computational Fluid Dynamics Analysis of Trigeminal Neuralgia Associated with the Vertebral Artery: A Report of Two Cases.

Trigeminal neuralgia is a nerve disorder that causes unilateral severe facial pain. The clinical features of trigeminal neuralgia are agonizing, paroxysmal, anticipated in one or more divisions of the trigeminal nerve, with repetitive bursts of a few seconds, exacerbated by cutaneous stimuli. Microvascular decompression is proven effective, resulting in a positive outcome. Here, we report two cases of trigeminal neuralgia associated with the vertebral artery, who underwent endoscopic microvascular decompression. This case report aims to show the benefit of computational fluid dynamics evaluation of the neurovascular contact and its effect on change in wall shear stress magnitude of the offending vertebral artery after surgical management with microvascular decompression.

Chloroxylon swietenia (Roxb.) DC induces cell death and apoptosis by down-regulating the NF-κB pathway in MCF-7 breast cancer cells: In vitro and in vivo investigations.

BACKGROUND: Natural products with targeted bioactivity have gained major attention in the field of cancer research owing to emerging anti-cancer drug resistance and off target toxicities. Chloroxylon swietenia (Roxb.) DC is recognized as a folklore medicinal plant and has numerous therapeutic benefits in the folklore medicine system, however the anti-cancer potential of this plant and its mechanism of action is poorly understood. AIMS: The aim of the study was to investigate the anti-breast cancer efficacy of C. swietenia leaves methanol extract (CSLME) against MCF-7 hormone dependent human breast cancer cell line with possible mechanism of action. METHODS AND RESULTS: The anti-breast cancer activity of CSLME against MCF-7 cells was assessed by evaluating its efficacy toward cytotoxicity, cell migration, colony formation, DNA fragmentation, apoptosis, cytoskeleton, angiogenesis, cell cycle regulation, and animal toxicity. The preliminary screening of CSLME against MCF-7 cells revealed the cytotoxicity (IC50 20 µg/ml), inhibited cell migration, colony formation, and angiogenesis. It was observed that CSLME induces apoptosis by nuclear fragmentation and disruption of cytoskeleton by actin derangement. The results of Annexin V-FITC assay and cell cycle analysis by flow cytometry clearly pointed out the sizable fraction of apoptotic cells, and arrested the cells at G2/M phase of cell cycle. The results of the immunoblotting experiments showed that CSLME activates intrinsic pathway of apoptosis with down regulation of anti-apoptotic marker like Bcl2, up regulation of pro-apoptotic markers like Bax & Bad, along with successful cleavage of Caspase-9 and PARP-1. Further, western blot analysis revealed the possible down regulation of NF-κB pathway by CSLME, which may be responsible for anti-cancer activity in MCF-7 cells. In vivo animal model studies using NOD-SCID mice demonstrated impressive anti-tumor activity with significant reduction in tumor volume of MCF-7 tumor xenograft. Of note, in-vivo acute oral toxicity study as per Organization for Economic Cooperation and Development 423 revealed the nontoxic nature of CSLME. CONCLUSION: The in vitro and in vivo findings clearly outline the potential of CSLME as inhibitor of growth and proliferation of MCF-7 cells. Mechanistically, CSLME seems to activate intrinsic pathway of apoptosis, arrest cell cycle, target actin cytoskeleton, inhibit growth, colony formation, migration, and angiogenesis, with down regulation of NF-κB pathway leading to cell death.

Dietary flavonoids inhibit the glycation of lens proteins: implications in the management of diabetic cataract.

The intervention of functional foods as complementary therapeutic approach for the amelioration of diabetes and sugar induced cataractogenesis is more appreciated over the present day chemotherapy agents owing to their nontoxic and increased bioavailability concerns. Dietary flavonoids, a class of bioactive phytochemicals is known to have wide range of biological activities against variety of human ailments. In the present study, we demonstrate anti-cataract effect of eight dietary flavonoids in sugar induced lens organ culture study. We present data on processes like inhibition of glycation-induced lens cloudiness, lens protein aggregation, glycation reaction and advanced glycation end products formation that can act as biochemical markers for this disease. The selected flavonoids were also tested for their aldose reductase (AR) inhibition (experimental and in silico). The molecular dynamics simulation results shed light on mechanistic details of flavonoid induced AR inhibition. The outcome of the present study clearly focuses the significance of kaempferol, taxifolin and quercetin as potential candidates for controlling diabetic cataract.

Inhibition of glycation and aldose reductase activity using dietary flavonoids: A lens organ culture studies.

On the eve of increasing incidence of diabetes mellitus and related complications, the search for novel, safe and alternatives therapeutic approaches are evolving. In the present investigation, a panel of ten dietary flavonoids such as 4'-methoxyflavanone, formononetin, hesperetin, hesperidin, naringenin, naringin, rutin, diadzin, silibinin and silymarin was evaluated as possible inhibitors of sugar induced cataractogenesis using bovine lens organ culture studies. The effect of selected flavonoids was observed on glycation induced lens opacity, AGE fluorescence, carbonyl group formation (a biomarker of glycation), protein aggregation and aldose reductase (AR) inhibition. The results obtained clearly demonstrate the efficacy of rutin and silibinin as promising leads for inhibition of glycation reaction and amelioration of sugar induced cataractogenesis. The findings of the present study may be useful for designing and development of the novel lead molecules for the management of diabetic cataract.

Effect of monohydroxylated flavonoids on glycation-induced lens opacity and protein aggregation.

Glycation-induced cataractogenesis and visual impairment is a major ophthalmic concern of altered sugar homeostasis in humans as well as animals. Searching antiglycating agents from natural sources is widely acknowledged as it can be made bioavailable through diet. The present study was designed to understand the positional suitability of hydroxylation in the flavonoid scaffold for maneuvering it as an anticataract agent. Six naturally occurring monohydroxylated flavonoids rataining hydroxylation at 3, 5, 6, 7, 2' and 4' carbon position were evaluated for their effect on glycation induced lens opacity, protein aggregation, carbonyl group formation and nontryptophan fluorescence. The selected flavonoids also evaluated for their aldose reductase inhibition: a key enzyme implicated in cataractogenesis. The results of this study clearly demonstrated the stereo-specificity of hydroxyl substitution and focused the significance of 7-hydroxy substitution as a lead scaffold. Overall, the test flavonoids demonstrated considerable anti-cataract activities in context with studied parameters.

Ethnomedicinal uses, phytochemistry and pharmacological properties of the genus Boerhavia.

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Boerhavia is widely distributed in tropical, subtropical and temperate regions of the world including Mexico, America, Africa, Asia, Indian Ocean Islands, Pacific Islands and Australia. The genus Boerhavia is extensively used by local peoples and medicinal practitioners for treatments of hepatitis, urinary disorders, gastro intestinal diseases, inflammations, skin problems, infectious diseases and asthma. Present review focused on traditional uses, phytochemistry, pharmacology and toxicology of Boerhavia genus to support potential scope for advance ethnopharmacological study. MATERIALS AND METHODS: Information on the Boerhavia species was collected from classical books on medicinal plants, pharmacopoeias and scientific databases like PubMed, Scopus, GoogleScholar, Web of Science and others. Also scientific literatures based on ethnomedicinal surveys, Ph.D. and M.Sc. dissertations, published papers from Elsevier, Taylor and Francis, Springer, ACS as well as Wiley publishers and reports by government bodies and documentations were assessed. RESULTS: A total of 180 compounds from Boerhavia genus were isolated of which B. diffusa alone shared around 131 compounds and for most of which it is currently an exclusive source. In the genus, phenolic glycosides and flavonoids contribute approximately 97 compounds. These includes eupalitin, rotenoids like boeravinones, coccineons, alkaloid i.e. betanin and punarnavine etc., showing vital pharmaceutical activities such as anticancer, anti-inflammatory, antioxidant and immunomodulatory. CONCLUSION: Boerhavia is an important genus with wide range of medicinal uses. However, most of the available scientific literatures have lacked relevant doses, duration and positive controls for examining bioefficacy of extracts and its active compounds. In some studies, taxonomic errors were encountered. Moreover, there is need for accurate methods in testing the safety and ethnomedicinal validity of Boerhavia species.

Role of dietary flavonoids in amelioration of sugar induced cataractogenesis.

Sugar induced cataractogenesis and visual impairment is more prominent ophthalmic problem in humans suffering from diabetes. Flavonoids have been identified as one of the therapeutically important class of phytochemicals possessing myriad of biological activities. Analyzing the anti-cataract effects of flavonoids from natural sources is an important aspect owing to their bioavailability in variety of dietary sources. In the present study a panel of ten dietary flavonoids like 3, 6-dihydroxy flavone, 3, 7-dihydroxy flavone, chrysin, 3-hydroxy-7-methoxy flavone, apigenin, genistein, baicalein, galangin, Biochanin-A, and diosmin were evaluated for their anti-cataract effects in sugar induced lens model studies. Series of parameters like role of flavonoids in glycation induced lens opacity, protein aggregation measurements, carbonyl group formation: a biochemical marker of glycation reaction, non-tryptophan fluorescence: a marker of formation of advanced glycation end products (AGEs) and assessment of (experimental and in silico) aldose reductase inhibition: a key enzyme of polyol pathway involved in cataractogenesis. The results of the study clearly demonstrated the impressive anti-cataract activity of chrysin followed by significant activity by apigenin, baicalein and genistein. The results of the present study may find applications in formulation of functional foods and neutraceuticals for the management of diabetic cataract.

Chitinases and Imaginal disc growth factors organize the extracellular matrix formation at barrier tissues in insects.

The cuticle forms an apical extracellular-matrix (ECM) that covers exposed organs, such as epidermis, trachea and gut, for organizing morphogenesis and protection of insects. Recently, we reported that cuticle proteins and chitin are involved in ECM formation. However, molecular mechanisms that control assembly, maturation and replacement of the ECM and its components are not well known. Here we investigated the poorly described glyco-18-domain hydrolase family in Drosophila and identified the Chitinases (Chts) and imaginal-disc-growth-factors (Idgfs) that are essential for larval and adult molting. We demonstrate that Cht and idgf depletion results in deformed cuticles, larval and adult molting defects, and insufficient protection against wounding and bacterial infection, which altogether leads to early lethality. We show that Cht2/Cht5/Cht7/Cht9/Cht12 and idgf1/idgf3/idgf4/idgf5/idgf6 are needed for organizing proteins and chitin-matrix at the apical cell surface. Our data indicate that normal ECM formation requires Chts, which potentially hydrolyze chitin-polymers. We further suggest that the non-enzymatic idgfs act as structural proteins to maintain the ECM scaffold against chitinolytic degradation. Conservation of Chts and Idgfs proposes analogous roles in ECM dynamics across the insect taxa, indicating that Chts/Idgfs are new targets for species specific pest control.

Efficient micropropagation and assessment of genetic fidelity of Boerhaavia diffusa L- High trade medicinal plant.

Boerhaavia diffusa L is a medicinal herb with immense pharmaceutical significance. The plant is used by many herbalist, Ayurvedic and pharmaceutical industries for production biopharmaceuticals. It is among the 46 medicinal plant species in high trade sourced mainly from wastelands and generally found in temperate regions of the world. However, the commercial bulk of this plant shows genetic variations which are the main constraint to use this plant as medicinal ingredient and to obtain high value products of pharmaceutical interest from this plant. In this study, we have regenerated the plant of Boerhaavia diffusa L through nodal explants and evaluated genetic fidelity of the micropropagated plants of Boerhaavia diffusa L with the help of random amplified polymorphic DNA (RAPD) markers. The results obtained using RAPD showed monomorphic banding pattern revealing genetic stability among the mother plant and in vitro regenerated plants of Boerhaavia diffusa L.

Development of novel pyrazolone derivatives as inhibitors of aldose reductase: an eco-friendly one-pot synthesis, experimental screening and in silico analysis.

Aldose reductase is the key enzyme of polypol pathway leading to accumulation of sorbitol. Sorbitol does not diffuse across the cell membranes easily and therefore accumulates within the cell, causing osmotic damage which leads to retinopathy (cataractogenesis), neuropathy and other diabetic complications. Currently, aldose reductase inhibitors like epalrestat, ranirestat and fidarestat are used for the amelioration of diabetic complications. However, such drugs are effective in patients having good glycemic control and less severe diabetic complications. In present study we have designed novel pyrazolone derivative and performed eco-friendly synthesis approach and tested the synthesized compounds as potential inhibitors of aldose reductase activity. Additional in silico analysis in current study indicates presence of highly conserved chemical environment in active site of goat lens aldose reductase. The reported data is expected to be useful for developing novel pyrazolone derivatives as lead compounds in the management of diabetic complications.

Evaluation of Vertical Bone Gain Following Alveolar Distraction Osteogenesis in the Anterior Edentulous Mandible: A Clinical Study.

AIM AND OBJECTIVES: To calculate the gain in bony height and volume of the distracted upper segment using an extraosseous unidirectional device to improve the retention of the future prosthesis. MATERIALS AND METHODS: Ten cases with completely or partially edentulous but severely or considerably resorbed anterior mandibles were managed by vertical alveolar distraction osteogenesis. All the patients were evaluated preoperatively, intraoperatively and post-operatively for various parameters clinically and radiographically i.e. on OPG, lateral cephalogram and on CT scan, at different time intervals. In all cases there was increase in vertical bone height. RESULTS: The study showed mean vertical bone gain (VBG) on OPG as 8.2 mm. The mean VBG on lateral cephalogram was 8.1 mm. The mean VBG on CT scan at right canine was 8.35 mm, at left canine was 8.2 mm and at midline was 8.27 mm. CONCLUSION: Alveolar distraction osteogenesis is a predictable method for restoring alveolar ridges prior to implant placement or prosthesis. Distraction osteogenesis is ideally suited for recreating missing tissue in the anterior esthetic zone by increasing vertical bone height as well as good width and soft tissue growth.

A prospective study involving the use of platelet rich plasma in enhancing the uptake of bone grafts in the oral and maxillofacial region.

ABSTRACT: Platelet-rich plasma (PRP) is an autologous product that contains highly concentrated number of platelets in a small volume of plasma, derived from whole blood by gradient density centrifugation. It has been speculated that local growth factors in human platelets (insulin-like growth factor, IGF; transforming growth factor, TGF-ß; platelet derived growth factor, PDGF) would enhance healing of grafts and also counteract resorption. The aim of this study was to evaluate efficacy of PRP on early healing after autogenous bone grafting. Of the twenty patients selected ten were treated with autogenous bone graft and PRP (PRP group) and other ten with autogenous bone graft alone (non-PRP group). PRP group consisted of two benign tumor of mandible, one post surgical defect, two unilateral alveolar cleft, one bilateral alveolar cleft with skeletal class III malocclusion, one maxillary hypoplasia, one oronasal fistula, one recurrent tumor of mandible, one multiple impacted mandibular teeth. Non-PRP group consisted of seven benign tumor of jaw, one keratocyst odontogenic tumor, one orbital blow out fracture, one residual traumatic defect. Biopsies were taken in the native bone, PRP treated grafted bone, grafted bone without PRP at 3 months to assess the maturity of bone. Radiographic imaging was performed by panoramic radiography at 3 and 6 months to evaluate bone opacity of grafted bone on comparison with native bone and computerized tomography at 6 months to evaluate grafted bone morphologically and to measure bone density in Hounsfield units. Microscopic results showed that significantly more matured bone was formed at PRP treated sites as that of native bone and immature bone in controls after 3 months of healing. Bone opacity of PRP treated bone grafts was close to that of native bone than that of non-PRP treated bone grafts on panoramic radiograph at 3 and 6 months. There was graft loss in three cases and graft resorption in one case of non-PRP treated bone grafts at 6 months. In PRP group the compact bone was clearly differentiated from cancellous bone as in native bone and thick in five cases, thin in five cases. In non-PRP group the compact bone was thin as a whole. Comparing native bone group and PRP group the CT value of PRP treated bone graft was more or less close to native bone group and comparing native bone group and non-PRP group CT value was low in non-PRP treated bone graft. Whereas when comparing PRP and non-PRP group CT value was higher in PRP group. Autologous PRP was a safe, biocompatible, effective, source for growth factors and carries no risk of transmissible diseases. It enhances and accelerates bone regeneration of autogenous bone grafts.

Soybean Knowledge Base (SoyKB): a web resource for soybean translational genomics.

BACKGROUND: Soybean Knowledge Base (SoyKB) is a comprehensive all-inclusive web resource for soybean translational genomics. SoyKB is designed to handle the management and integration of soybean genomics, transcriptomics, proteomics and metabolomics data along with annotation of gene function and biological pathway. It contains information on four entities, namely genes, microRNAs, metabolites and single nucleotide polymorphisms (SNPs). METHODS: SoyKB has many useful tools such as Affymetrix probe ID search, gene family search, multiple gene/metabolite search supporting co-expression analysis, and protein 3D structure viewer as well as download and upload capacity for experimental data and annotations. It has four tiers of registration, which control different levels of access to public and private data. It allows users of certain levels to share their expertise by adding comments to the data. It has a user-friendly web interface together with genome browser and pathway viewer, which display data in an intuitive manner to the soybean researchers, producers and consumers. CONCLUSIONS: SoyKB addresses the increasing need of the soybean research community to have a one-stop-shop functional and translational omics web resource for information retrieval and analysis in a user-friendly way. SoyKB can be publicly accessed at http://soykb.org/.

Comparison of preauricular approach versus retromandibular approach in management of condylar fractures.

AIM: The aim of the study is to compare the two extra oral approaches to the TMJ viz preauricular and retromandibular approach in management of condylar fractures of mandible. METHODS AND MATERIALS: Patients with fractured dislocation and displacement of mandible condyle in medial direction were managed by preauricular approach. Patients with lateral displacement of mandibular condyle were managed by retromandibular approach. OPG, Reverse towne's, and C.T. scan were taken in all the cases prior to surgery to assess the pattern of displacement. RESULTS: In our study both approaches have given excellent access and visibility to the condylar fractures but with limitations in each technique. Minimal intraoperative and postoperative complications were encountered in both approaches. The duration of the procedure for preauricular approach was much longer when compared with retromandibular approach. Facial nerve weakness was common in patients treated with preauricular approach, which they improved over a period of time and had complete recovery. Postoperative scar was imperceptible in all cases and good cosmetic results were seen with both approaches. Mouth opening, mandibular movements and occlusion were more or less same in both the approaches while pain and clicking was common in preauricular approach. CONCLUSION: Both approaches have good results in managing condylar fractures with retromandibular approach having ease of access and ease of fixation. So one can always give preference to retromandibular approach over preauricular approach in managing the condylar fracture except in some cases where preauricular approach is the only option like anteromedial dislocation or complete medial dislocation of condylar segment. Situations, where patients who reported very late for the surgery with resultant scarring of the tissue, in those cases preauricular approach is the only option.