Does the Surgical Intervention for Trigeminal Neuralgia Refractory to Pharmacotherapy Improve Quality-of-Life? - A Systematic Review.

PURPOSE: Trigeminal neuralgia (TN) refractory to pharmacotherapy requires surgical interventions which vary from percutaneous procedure to microvascular decompression (MVD). The aim of the systematic review is to find evidence for the surgical treatment for TN with high success rate and low complications which improves the quality-of-life (QOL). METHODS: A systematic literature search was made on published studies from MEDLINE, SCOPUS, Science Direct, and Cochrane Library databases that report the available surgical treatment for TN up to March 2020 and studies referred in the selected papers. Relevant studies were selected based on predefined eligibility criteria. The primary outcome measured was success rate, pain relief and secondary outcome measured was QOL, recurrence and complication rate. RESULTS: Ten studies with a sum of 11,154 individuals were included in this qualitative analysis. Seven studies compared MVD whereas 4 studies compared Gamma knife radiosurgery with other techniques like percutaneous balloon compression, percutaneous glycerol rhizotomy etc. The result showed that MVD has a considerable higher rate of initial pain-free outcomes (96.6%) followed by Gamma knife radiosurgery (96.2%), cryotherapy (95.4%), percutaneous balloon compression (87%), percutaneous glycerol rhizotomy (85%) and the lowest rate of cohorts who were never pain-free (1.7%).QOL was improved to 100% as a result of pain relief which was evaluated in only 2 studies . Overall the recurrence rate was 0.45 to 52%. MVD has lower rate of long-term recurrence 0.45 and 6.1% for 2 years and 8 years, respectively, and cryotherapy has the highest rate of 52% at 6 months. CONCLUSION: Outcomes of the literature search showed that it lacks the knowledge to generally support 1 or the other treatment. Each type of TN requires individualized protocols to treat based on pain response which ultimately improve the QOL. We also propose there should be more reliable data reporting by using a universally acceptable pain scale for better analysis of treatment outcome.

Aesthetic and Functional Rehabilitation of Postburn Maxillofacial Deformity.

Postburn maxillofacial deformities, although rare, are a significant cause of morbidity. Since contracture scars have a potential role in deforming the maxillofacial skeleton, the focus of treatment should be on growing patients, where scar contractures can drastically influence growth and morphology of the maxillofacial units. There are certain aspects of severe facial burns and deformities, especially of the jaws, that deserve sincere attention to overcome aesthetic and functional disabilities such as inability to masticate and incompetent lips. The purpose of this article, therefore, is to discuss these injuries, the mechanism of development of deformities of the jaws and associated structures and their management for better aesthetic, functional, and psychological health of patient. An interpretive clinical report is presented.

Effect of distal sugar and interglycosidic linkage of disaccharides on the activity of proline rich antimicrobial glycopeptides.

The effect of glycosylation on protein structure and function depends on a variety of intrinsic factors including glycan chain length. We have analyzed the effect of distal sugar and interglycosidic linkage of disaccharides on the properties of proline-rich antimicrobial glycopeptides, formaecin I and drosocin. Their glycosylated analogs-bearing lactose, maltose and cellobiose, as a glycan side chain on their conserved threonine residue, were synthesized where these disaccharides possess identical proximal sugar and vary in the nature of distal sugar and/or interglycosidic linkage. The structural and functional properties of these disaccharide-containing formaecin I and drosocin analogs were compared with their corresponding monoglycosylated forms, ß-D-glucosyl-formaecin I and ß-D-glucosyl-drosocin, respectively. We observed neither major secondary structural alterations studied by circular dichroism nor substantial differences in the toxicity with mammalian cells among all of these analogs. The comparative analyses of antibacterial activities of these analogs of formaecin I and drosocin displayed that ß-D-maltosyl-formaecin I and ß-D-maltosyl-drosocin were more potent than that of respective ß-D-Glc-analog, ß-D-cellobiosyl-analog and ß-D-lactosyl-analog. Despite the differences in their antibacterial activity, all the analogs exhibited comparable binding affinity to DnaK that has been reported as one of the targets for proline-rich class of antibacterial peptides. The comparative-quantitative internalization studies of differentially active analogs revealed the differences in their uptake into bacterial cells. Our results exhibit that the sugar chain length as well as interglycosidic linkage of disaccharide may influence the antibacterial activity of glycosylated analogs of proline-rich antimicrobial peptides and the magnitude of variation in antibacterial activity depends on the peptide sequence.

Synthesis and evaluation of a fluorescent non-peptidic cholecystokinin-B/gastrin receptor specific antagonist for cancer cell imaging.

Fluorescent labeling has enabled a better understanding of the relationships between receptor location, function, and life cycle. Each of these perspectives contributes new insights into drug action, particularly for G protein-coupled receptors (GPCRs). The aim of this study was to develop a fluorescein derivative, FLUO-QUIN-a novel antagonist of the cholecystokinin-B/gastrin receptor. A radioligand-binding experiment revealed an IC(50) of 4.79 nm, and the antagonist inhibited gastric acid secretion in an isolated lumen-perfused mouse stomach assay (up to 51 % at 100 nm). The fluorescence properties altered upon binding to the receptor, and the fluorophore was quenched to a greater extent when free than in the bound form. FLUO-QUIN specifically bound to human pancreatic carcinoma cells, MiaPaca-2, which are known to express the receptor, as evidenced by rapid clustering followed by time-dependent receptor internalization. This proves the stability of FLUO-QUIN and its ability to penetrate vesicular membranes and reach various cell targets. Hence it might be used as an agent for the detection of CCK-B-receptor-positive tumors by fluorescence imaging.

Glycosylated analogs of formaecin I and drosocin exhibit differential pattern of antibacterial activity.

The synthetic glycopeptides are interesting model systems to study the effect of O-glycosylation in modulating their function and structure. A series of glycosylated analogs of two antibacterial peptides, formaecin I and drosocin, were synthesized by varying the nature of sugar and its linkage with bioactive peptides to understand the influence of structure variation of glycosylation on their antibacterial activities. Higher antibacterial activities of all glycopeptides compared to their respective non-glycosylated counterparts emphasize in part the importance of sugar moieties in functional implications of these peptides. The consequences of the unique differences among the analogs were apparent on their antibacterial activities but not evident structurally by circular dichroism studies. We have shown that differently glycosylated peptides exhibit differential effect among each other when tested against several Gram-negative bacterial strains. The change of monosaccharide moiety and/or its anomeric configuration in formaecin I and drosocin resulted into decrease in the antibacterial activity in comparison to that of the native glycopeptide, but the extent of decrease in antibacterial activity of glycosylated drosocin analogs was less. Probably, the variation in peptide conformation arising due to topological dissimilarities among different sugars in the same peptide resulting in possible modulation in binding properties appears to be responsible for differences in their antibacterial activities. Indeed, these effects of glycosylation are found to be sequence-specific and depend in the milieu of amino acid residues. Interestingly, none of the carbohydrate variants affected the basic property of these peptides, which is non-hemolytic and non-toxicity to eukaryotic cells.

Comparative evaluation of Low Level Laser Therapy and cryotherapy in pain control and wound healing following orthodontic tooth extraction: A double blind study.

PURPOSE: To compare and evaluate pain and healing following orthodontic tooth extraction using Low Level Laser Therapy [LLLT] and Cryotherapy. MATERIALS AND METHODS: 62 patients referred for orthodontic extraction of bilateral bicuspids were included. Subjects were alternatively divided into two groups with 31 patients each. One of the bilateral extraction sites was subjected to either intervention, LLLT or Cryotherapy, while the other site was kept as control. Pain was assessed for 7 consecutive days by Visual Analogue Scale and Wound healing on 4th, 7th and 14th days using a modified wound healing scale. RESULTS: Pain scores were generally better for Group I [LLLT] when compared to Group II [Cryotherapy] on all days. The highest mean score for pain observed on the 1st post-extraction day was 4.00 ± 0.93 and 4.16 ± 0.93 for Group I and Group II respectively [p = 0.42]. It was also observed that LLLT helped in better wound healing as compared to cryotherapy with a significant difference in wound healing on 7th [mean score for Group I and Group II- 1.16 ± 0.52 and 1.6 ± 0.62 respectively: p = 0.01] and 14th [mean score Group I and Group II- 0.23 ± 0.43 and 1.0 ± 0.58 respectively: p = 0.00] post-extraction days. CONCLUSION: LLLT has better analgesic and wound healing properties as compared to Cryotherapy, suggesting that LLLT should be preferred over cryotherapy whenever possible.

The removal of pentavalent arsenic by graphite intercalation compound functionalized carbon foam from contaminated water.

In the present investigation, Graphite intercalation compound (GIC) functionalized phenolic resin based carbon foam for removal of arsenic (As(V)) from contaminated water is developed by sacrificial template technique followed by carbonization at 1000 °C in N2. The GICCF adsorbent is characterised by scanning electron microscope (SEM) for morphological study, X-ray diffraction (XRD) patterns explains the phase information and interlayer spacing of the adsorbent, whereas Fourier Transform Infrared Spectroscopy (FTIR) and X-ray Photoelectron Spectroscopy (XPS) gives the information about surface functionality and mechanism of adsorption of As(V) over the surface of adsorbent. The time data is fitted well in pseudo second order kinetics and follows multilinear nature of intra-particle diffusion model. The adsorption nature of adsorbent and adsorbate is explained by Langmuir isotherm better than Freundlich isotherm, Temkin isotherm, and D-R isotherm. The adsorption capacity of adsorbent is 62.5 µgg-1, which is calculated by Langmuir isotherm. Arsenic removal by GICCF is taken place within two hrs up to acceptable limit. The proposed GICCF can be regenerated after treating with 0.1 M HNO3 and 0.1 M HCl solution and it can be used for multiple times.

Is the routine practice of antibiotic prescription and microbial culture and antibiotic sensitivity testing justified in primary maxillofacial space infection patients? A prospective, randomized clinical study.

PURPOSE: The purpose of this prospective, randomized, comparative clinical study was to compare treatment outcome of removal of foci and incision and drainage, with or without oral antibiotic therapy, in the management of single primary maxillofacial space infection with a known focus. MATERIALS AND METHODS: A total of 40 patients with single primary maxillofacial space infection with a known infectious focus were divided into two groups, one treated with incision and drainage only, and the other with incision and drainage along with oral antibiotics. The focus of infection was addressed in both groups. Parameters evaluated included pain score, maximum mouth opening, swelling, purulent discharge and return to normal life, which were assessed on days 1, 2, 3, 5 and 7. The patients were followed up until they reported return to normal life as assessed by a questionnaire. RESULTS: All of the patients rapidly responded to treatment as observed by a reduction in pain, swelling, discharge, and improvement in mouth opening. Pus discharge stopped within first 3 days in 75% of patients. The patients who underwent immediate extraction showed a faster resolution of infection (mean return to normal life = 9 days) than others (mean = 11.2 days). There was no statistically significant difference between the two groups for the five study parameters (p < 0.05). Of the total pus specimens, 75% had no significant bacterial growth, or grew 'oral flora'/contaminants, while only 25% grew specific bacteria. CONCLUSION: This study questions the conventional practice by dental practitioners and surgeons of prescribing antibiotics to all patients with odontogenic infection. Microbial culture and antibiotic sensitivity is of little therapeutic value in selected patient groups.

Identification of potent cholecystokinin-B receptor antagonists: synthesis, molecular modeling and anti-cancer activity against pancreatic cancer cells.

Advanced malignant stages of pancreatic cancer have poor prognosis and very few treatment strategies are available. Pancreatic cancer is known to possess unique growth-related receptors that when activated, stimulate tumour proliferation. Gastrin and its related peptide cholecystokinin (CCK) are also significantly involved in the growth of this cancer type as well as other malignancies through activation of the cholecystokinin-B receptor (CCK-BR). New treatment strategies with CCK-BR antagonists are being suggested that suppress the growth promoting effects of gastrin. In this paper, we report the development of two series of quinazolinone derivatives incorporating hydrazinecarbothioamide (compounds 3a-g) and the hydrazino group (compounds 4a-e) as linkers for developing CCK-BR antagonists. The affinities of the compounds were determined using docking into the CCK-BR homology modeled structure. The compounds were tested for in vitro CCK-BR binding and gastric acid secretion in an isolated lumen-perfused mouse stomach assay. The compounds exhibited CCK-BR binding activity (IC50) in the range of 0.2-975 nM and showed good gastric acid secretion inhibitory activity. Molecular modeling of the compounds was done and pharmacophore mapping results showed good prediction of in vitro activity which correlated well with the experimental antagonistic activity. The compounds were further tested for their cytotoxicity on CCK-BR expressing pancreatic cancer cells. The results of the study provided two potent CCK-BR antagonists which also possess good to moderate growth inhibitory activities against pancreatic cancer cells.

Lightweight and Easily Foldable MCMB-MWCNTs Composite Paper with Exceptional Electromagnetic Interference Shielding.

Lightweight and easily foldable with high conductivity, multiwalled carbon nanotube (MWCNT)-based mesocarbon microbead (MCMB) composite paper is prepared using a simple, efficient, and cost-effective strategy. The developed lightweight and conductive composite paper have been reported for the first time as an efficient electromagnetic interference (EMI) shielding material in X-band frequency region having a low density of 0.26 g/cm(3). The investigation revealed that composite paper shows an excellent absorption dominated EMI shielding effectiveness (SE) of -31 to -56 dB at 0.15-0.6 mm thickness, respectively. Specific EMI-SE of as high as -215 dB cm(3)/g exceeds the best values of metal and other low-density carbon-based composites. Additionally, lightweight and easily foldable ability of this composite paper will help in providing stable EMI shielding values even after constant bending. Such intriguing performances open the framework to designing a lightweight and easily foldable composite paper as promising EMI shielding material, especially in next-generation devices and for defense industries.

Understanding the importance of glycosylated threonine and stereospecific action of Drosocin, a Proline rich antimicrobial peptide.

Glycosylation is an essential post-translational modification for few antimicrobial peptides of Proline rich class. In the present study we have shown the importance of Thr glycosylation over Ser glycosylation in Drosocin. Difference of a methyl group makes glycosylated-Thr preferred over glycosylated-Ser and renders higher activity to the peptide, probably due to the rigid conformation provided by the glycosylated-Thr. The structural rigidity provided by glycosylated-Thr to Drosocin backbone was mimicked by substituting glycosylated-Thr11, Ser7 and Ser12 with Pro residues. The designed non-glycosylated analogue, P(7)P(11)P(12)-Drosocin, exhibited functional and structural properties similar to that of the native monoglycosylated peptide. The functional importance of stereospecificity of amino acids and sugar was further explored. Interestingly, (all D) p(7)p(11)p(12)-Drosocin failed to exhibit antimicrobial activity but had comparable binding affinity to DnaK, one of the proposed targets for Proline rich class of antibacterial peptides, as that of its L counterpart. However, Drosocin containing either L or D enantiomeric sugar, displayed antimicrobial activity and binding affinity to bacterial heat shock protein, DnaK. The flow cytometry (FACS) experiments revealed the internalization of Drosocins bearing enantiomeric sugars and P(7)P(11)P(12)-Drosocin but not of its d-enantiomer into bacteria suggesting the importance of stereospecificity of amino acids for membrane entry. Once internalized both enantiomeric peptides may behave similarly. This assumption was corroborated by in vitro activity of (all D) p(7)p(11)p(12)-Drosocin in cell free assay where it abrogated transcription/translation pathway similar to l-enantiomer but could not inhibit the same in whole cell assay. These research findings provide insights into the mode of action of Proline rich class of antibacterial peptides and guidelines for designing functionally equivalent non-glycosylated analogues of glycosylated antibacterial peptides.

Novel 99mTc radiolabeled quinazolinone derivative [Qn-In]: synthesis, evaluation and biodistribution studies in mice and rabbit.

A quinazolinone derivative as a novel non-peptidic CCK-B receptor antagonist designated as Qn-In, was synthesized, characterized by spectroscopic techniques and evaluated for radiopharmaceutical potential. The efficiency of labeling with (99m)Tc was greater than 98% and the complex was stable for about 7 hours at 37 degrees C in presence of serum. Affinity of Qn-In was determined to be in nanomolar range by competitive binding studies on cancer cell line MDA-MB-468. Bio-distribution of (99m)Tc labeled Qn-In in mice was examined by intravenous administration and time-activity curves were generated. The ligand showed binding to most of the organs, known to express CCK-B receptor. The lack of uptake in brain may be due to the inability of the complex to cross the blood-brain barrier. Our results show that (99m)Tc labeled Qn-In ligand provides a new template for further development of non-peptidic ligands for diagnosis and therapy of diseases related with CCK-B receptor.