Frequency of Lingual Nerve Injury after the Removal of Impacted Mandibular Third Molar

Objective: to determine the frequency of lingual nerve injury after the removal of impacted mandibular 3rd molar. Study Design: Cross sectional study Place and duration: outdoor patient department of Oral and Maxillofacial Surgery Hitec Dental College, Foundation College of Dentistry Peace Gernal Hospital, Nishtar Institute of  Dentistry,Multan from January 2018 to January 2019 in one year duration. Results: Study included 335 patients with mean age of 20.86+ 1.95 yrs. Males were 190(56.7%) and females were 145(43.3%).lingual nerve injury was found in 28 patients(8.4%)while it was absent in 307 patients(91.6%).There was no significant effect was found on the frequency of lingual nerve injury for age or gender of the patient population. Conclusion: Lingual nerve injury is a commonly encountered complication among those undergoing extraction of impacted third molar. It should be carefully sought in all the patients undergoing the surgical procedure and improvement in surgical skills and techniques needs to be emphasized to further reduce the incidence and risk of this complication. Keywords: Impacted third molar, Lingual nerve, OPG (orthopantomogram), Dentistry, Mandible. DOI: 10.7176/JMPB/57-01 Publication date: July 31st 201

Metoprolol-eudragit microcapsules: pharmacokinetic study using convolution approach

The objective of this study was to employ convolution approach for the calculation of blood drug levels for various release types (1:1, 1:1.5, and 1:2, drug:polymer) of metoprolol tartrate microparticulate formulations from in vitro drug dissolution profiles. Using USP 2007 dissolution apparatus II, dissolution testing was carried out by employing sequential pH change method with and without 0.5 % soudium lauryl sulphate, surfactant. The values of derived pharmacokinetic parameters like Cmax (Maximum blood drug concentration), Tmax (Time needed to reach maximum blood drug concentration), and AUC (area under blood drug concentration curve) from the predicted drug concentration in blood were amazingly comparable to that calculated from the corresponding human in vivo data as stated in literature. As per conclusion, convolution approach is a useful analytical tool for computing drug concentration in blood as well as for evaluating product quality.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Design and Evaluation of Modified Release Bilayer Tablets of Flurbiprofen Projekt i ocena dwuwarstwowych tabletek flurbiprofenu o zmodyfikowanym uwalnianiu

Abstract Objectives. To design and evaluate modified release bilayer tablets of flurbiprofen. Material and Methods. In this study, bilayer modified release (MR) tablets of flurbiprofen were formulated using ethyl cellulose (EC) and polyvinylpyrrolidone (PVP) in different ratios as release retardant materials using a wet granulation method. In vitro release studies were done in dissolution media of varying pH i.e. pH 1.2, 4.5, 7.0 and 7.5. Results. All tablets exhibited good physical quality with respect to appearance, content uniformity, hardness, weight variation and friability. In vitro dissolution data showed that increasing proportions of EC retarded whereas increasing PVP enhanced the drug release rate. The bilayer MR tablets showed an initial release of approximately 35% (i.e. 100 mg drug) in about 1 h, then sustaining the release for 12 h, ending up with 89.56% and 96.12% for formulation MR1 and MR2, respectively. The kinetic analysis of dissolution data showed that zero order release was observed in these tablets. When data was fitted to the Korsmeyer-Peppas model, a non-Fickian transport was observed with the MR tablets. A model independent approach showed that as the release rate increases, the MDT decreases, showing the retarding behavior of the non-biodegradable polymers employed in formulation development. Conclusions. Bilayer modified release tablets of flurbiprofen can be successfully formulated using ethylcellulose and polyvinylpyrrolidone in different ratios as release retardant materials employing a wet granulation method (Adv Clin Exp Med 2011, 20, 3, 343-349). Key words: ethylcellulose, polyvinylpyrrolidone, wet granulation method, non-Fickian release. Streszczenie Cel pracy. Zaprojektowanie i ocena dwuwarstwowych tabletek flurbiprofenu o zmodyfikowanym uwalnianiu. Materiał i metody. W badaniu tym dwuwarstwowe tabletki flurbiprofenu o zmodyfikowanym uwalnianiu (MR) zostały stworzone z użyciem etylocelulozy (EC) i poliwinylopirolidonu (PVP) w różnych proporcjach jako środki opóźniające uwolnienie metodą mokrej granulacji. W badaniach uwalniania in vitro użyto środków rozpuszczają-cych o różnym pH, tj. pH 1,2; 4,5; 7,0 i 7,5. Wyniki. Wszystkie tabletki miały dobre fizyczne właściwości w odniesieniu do wyglądu, jednolitości zawartości, twardości, wahań wagi i kruszenia. W badaniach in vitro wykazano, że zwiększenie zawartości EC spowalniało, a zwiększenie zawartości PVP przyspieszało tempo uwalniania leku. Dwuwarstwowe tabletki MR wykazały począt-kowo uwalnianie ok. 35% (tj. 100 mg leku) w ciągu około 1 godz., a następnie utrzymanie rozpuszczenia przez 12 godz., kończąc na 89,56 i 96,12% dla preparatów MR1 i MR2. Analiza kinetyczna danych na temat rozpuszczania pokazała, że w tych tabletkach wystąpiło uwalnianie rzędu zerowego. Gdy dane dopasowano do modelu Korsmeyera-Peppasa, obserwowano transport masy tabletek MR niezgodny z prawem Ficka. Niezależne podejście wykazało, że w miarę wzrostu szybkości uwalniania, MDT zmniejsza się, co pokazuje opóźniające działanie nieulegających biodegradacji polimerów stosowanych w produkcji preparatu. Wnioski. Dwuwarstwowe tabletki o zmodyfikowanym uwalnianiu flurbiprofenu z powodzeniem można produkować, stosując etylocelulozę i poliwinylopirolidon w różnych proporcjach jako środki opóźniające uwolnienie metodą mokrej granulacji Słowa kluczowe: etyloceluloza, poliwinylopirolidon, metoda mokrej granulacji, uwalnianie niezgodne z prawem Ficka

In silico modeling of the specific inhibitory potential of thiophene-2,3-dihydro-1,5-benzothiazepine against BChE in the formation of β-amyloid plaques associated with Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease, known to be associated with the gradual loss of memory, is characterized by low concentration of acetylcholine in the hippocampus and cortex part of the brain. Inhibition of acetylcholinesterase has successfully been used as a drug target to treat Alzheimer's disease but drug resistance shown by butyrylcholinesterase remains a matter of concern in treating Alzheimer's disease. Apart from the many other reasons for Alzheimer's disease, its association with the genesis of fibrils by β-amyloid plaques is closely related to the increased activity of butyrylcholinesterase. Although few data are available on the inhibition of butyrylcholinesterase, studies have shown that that butyrylcholinesterase is a genetically validated drug target and its selective inhibition reduces the formation of β-amyloid plaques.</p> <p>Rationale</p> <p>We previously reported the inhibition of cholinesterases by 2,3-dihydro-1, 5-benzothiazepines, and considered this class of compounds as promising inhibitors for the cure of Alzheimer's disease. One compound from the same series, when substituted with a hydroxy group at C-3 in ring A and 2-thienyl moiety as ring B, showed greater activity against butyrylcholinesterase than to acetylcholinesterase. To provide insight into the binding mode of this compound (Compound A), molecular docking in combination with molecular dynamics simulation of 5000 ps in an explicit solvent system was carried out for both cholinesterases.</p> <p>Conclusion</p> <p>Molecular docking studies revealed that the potential of Compound A to inhibit cholinesterases was attributable to the cumulative effects of strong hydrogen bonds, cationic-π, π-π interactions and hydrophobic interactions. A comparison of the docking results of Compound A against both cholinesterases showed that amino acid residues in different sub-sites were engaged to stabilize the docked complex. The relatively high affinity of Compound A for butyrylcholinesterase was due to the additional hydrophobic interaction between the 2-thiophene moiety of Compound A and Ile69. The involvement of one catalytic triad residue (His438) of butyrylcholinesterase with the 3'-hydroxy group on ring A increases the selectivity of Compound A. C-C bond rotation around ring A also stabilizes and enhances the interaction of Compound A with butyrylcholinesterase. Furthermore, the classical network of hydrogen bonding interactions as formed by the catalytic triad of butyrylcholinesterase is disturbed by Compound A. This study may open a new avenue for structure-based drug design for Alzheimer's disease by considering the 3D-pharmacophoric features of the complex responsible for discriminating these two closely-related cholinesterases.</p

Effects of antibiotic resistance, drug target attainment, bacterial pathogenicity and virulence, and antibiotic access and affordability on outcomes in neonatal sepsis: an international microbiology and drug evaluation prospective substudy (BARNARDS)

Background Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin–gentamicin as first-line therapy for the management of neonatal sepsis. In the BARNARDS observational cohort study of neonatal sepsis and antimicrobial resistance in LMICs, common sepsis pathogens were characterised via whole genome sequencing (WGS) and antimicrobial resistance profiles. In this substudy of BARNARDS, we aimed to assess the use and efficacy of empirical antibiotic therapies commonly used in LMICs for neonatal sepsis. Methods In BARNARDS, consenting mother–neonates aged 0–60 days dyads were enrolled on delivery or neonatal presentation with suspected sepsis at 12 BARNARDS clinical sites in Bangladesh, Ethiopia, India, Pakistan, Nigeria, Rwanda, and South Africa. Stillborn babies were excluded from the study. Blood samples were collected from neonates presenting with clinical signs of sepsis, and WGS and minimum inhibitory concentrations for antibiotic treatment were determined for bacterial isolates from culture-confirmed sepsis. Neonatal outcome data were collected following enrolment until 60 days of life. Antibiotic usage and neonatal outcome data were assessed. Survival analyses were adjusted to take into account potential clinical confounding variables related to the birth and pathogen. Additionally, resistance profiles, pharmacokinetic–pharmacodynamic probability of target attainment, and frequency of resistance (ie, resistance defined by in-vitro growth of isolates when challenged by antibiotics) were assessed. Questionnaires on health structures and antibiotic costs evaluated accessibility and affordability. Findings Between Nov 12, 2015, and Feb 1, 2018, 36 285 neonates were enrolled into the main BARNARDS study, of whom 9874 had clinically diagnosed sepsis and 5749 had available antibiotic data. The four most commonly prescribed antibiotic combinations given to 4451 neonates (77·42%) of 5749 were ampicillin–gentamicin, ceftazidime–amikacin, piperacillin–tazobactam–amikacin, and amoxicillin clavulanate–amikacin. This dataset assessed 476 prescriptions for 442 neonates treated with one of these antibiotic combinations with WGS data (all BARNARDS countries were represented in this subset except India). Multiple pathogens were isolated, totalling 457 isolates. Reported mortality was lower for neonates treated with ceftazidime–amikacin than for neonates treated with ampicillin–gentamicin (hazard ratio [adjusted for clinical variables considered potential confounders to outcomes] 0·32, 95% CI 0·14–0·72; p=0·0060). Of 390 Gram-negative isolates, 379 (97·2%) were resistant to ampicillin and 274 (70·3%) were resistant to gentamicin. Susceptibility of Gram-negative isolates to at least one antibiotic in a treatment combination was noted in 111 (28·5%) to ampicillin–gentamicin; 286 (73·3%) to amoxicillin clavulanate–amikacin; 301 (77·2%) to ceftazidime–amikacin; and 312 (80·0%) to piperacillin–tazobactam–amikacin. A probability of target attainment of 80% or more was noted in 26 neonates (33·7% [SD 0·59]) of 78 with ampicillin–gentamicin; 15 (68·0% [3·84]) of 27 with amoxicillin clavulanate–amikacin; 93 (92·7% [0·24]) of 109 with ceftazidime–amikacin; and 70 (85·3% [0·47]) of 76 with piperacillin–tazobactam–amikacin. However, antibiotic and country effects could not be distinguished. Frequency of resistance was recorded most frequently with fosfomycin (in 78 isolates [68·4%] of 114), followed by colistin (55 isolates [57·3%] of 96), and gentamicin (62 isolates [53·0%] of 117). Sites in six of the seven countries (excluding South Africa) stated that the cost of antibiotics would influence treatment of neonatal sepsis

Molecular Docking and Quantitative Structure Activity Relationship (QSAR) Studies of Some Newly Synthesized Poly (Azomethine) Esters

Molecular docking procedure is well known for the investigation of small molecules; however, for macromolecules, it has attained limited success so far. Thus, in an attempt, a series of poly (azomethine) esters was synthesized in a laboratory, and their model oligomer units were studied by computer-aided computational MOE software package to investigate, specifically, binding modes that could influence their anticancer activities. Poly (azomethine) ester (PAME) was prepared by solution phase polycondensation of a preformed Schiff base (SB) 4-((4-(4-(4-hydroxybenzylideneamino)phenoxy)phenylimino)methyl) phenol with terephthaloyl chloride (TC). Terpolymers (PAMEF, PAMEB, PAMESi, PAMEPr, and PAMEH) were synthesized by the incorporation of various moieties along with TC and SB in the main chain. Structural elucidation was carried out by spectroscopic studies and elemental analysis. Docking procedure, adopted to investigate anticancer activity, showed that material was docked in the same pocket of active site as by anticancer protein complex (PDB code: 1T69). Molecular docking along with the quantitative structure activity relationship (QSAR) investigations showed groove binding as a preferred mode between the material and double-stranded DNA (PDB ID-1BNA). Binding strength indicated worthy correlation with various physicochemical parameters of the material like hydrophobic surface area (Vsurf), EHOMO, ELUMO, log P, and molar refractivity (MR). Calculated values for the formation constant (Kf) showed good binding strength for polymer-DNA complex. Consequently, the synthesized material is expected to exhibit anticancer activities and could be studied further as anticancer drugs

Thigh-length compression stockings and DVT after stroke

Controversy exists as to whether neoadjuvant chemotherapy improves survival in patients with invasive bladder cancer, despite randomised controlled trials of more than 3000 patients. We undertook a systematic review and meta-analysis to assess the effect of such treatment on survival in patients with this disease