• Investigation of Plasma Treatment on Micro-Injection Moulded Microneedle for Drug Delivery

      Nair, Karthik Jayan; Whiteside, Benjamin R.; Grant, Colin A.; Patel, Rajnikant; Tuinea-Bobe, Cristina-Luminita; Norris, Keith; Paradkar, Anant R. (2015-10-30)
      Plasma technology has been widely used to increase the surface energy of the polymer surfaces for many industrial applications; in particular to increase in wettability. The present work was carried out to investigate how surface modification using plasma treatment modifies the surface energy of micro-injection moulded microneedles and its influence on drug delivery. Microneedles of polyether ether ketone and polycarbonate and have been manufactured using micro-injection moulding and samples from each production batch have been subsequently subjected to a range of plasma treatment. These samples were coated with bovine serum albumin to study the protein adsorption on these treated polymer surfaces. Sample surfaces structures, before and after treatment, were studied using atomic force microscope and surface energies have been obtained using contact angle measurement and calculated using the Owens-Wendt theory. Adsorption performance of bovine serum albumin and release kinetics for each sample set was assessed using a Franz diffusion cell. Results indicate that plasma treatment significantly increases the surface energy and roughness of the microneedles resulting in better adsorption and release of BSA.
    • Investigation of Pulse electric field effect on HeLa cells alignment properties on extracellular matrix protein patterned surface

      Jamil, M. Mahadi Abdul; Zaltum, M.A.M.; Rahman, N.A.A.; Ambar, R.; Denyer, Morgan C.T.; Javed, F.; Sefat, Farshid; Mozafari, M.; Youseffi, Mansour (2018)
      Cell behavior in terms of adhesion, orientation and guidance, on extracellular matrix (ECM) molecules including collagen, fibronectin and laminin can be examined using micro contact printing (MCP). These cell adhesion proteins can direct cellular adhesion, migration, differentiation and network formation in-vitro. This study investigates the effect of microcontact printed ECM protein, namely fibronectin, on alignment and morphology of HeLa cells cultured in-vitro. Fibronectin was stamped on plain glass cover slips to create patterns of 25μm, 50μm and 100μm width. However, HeLa cells seeded on 50μm induced the best alignment on fibronectin pattern (7.66° ±1.55SD). As a consequence of this, 50μm wide fibronectin pattern was used to see how fibronectin induced cell guidance of HeLa cells was influenced by 100μs and single pulse electric fields (PEF) of 1kV/cm. The results indicates that cells aligned more under pulse electric field exposure (2.33° ±1.52SD) on fibronectin pattern substrate. Thus, PEF usage on biological cells would appear to enhance cell surface attachment and cell guidance. Understanding this further may have applications in enhancing tissue graft generation and potentially wound repair.
    • An Investigation of the Diels-Alder Cycloadditions of 2(H)-1,4-Oxazin-2-ones.

      Afarinkia, Kamyar; Bahar, A.; Bearpark, M.J.; Garcia-Ramos, J.; Ruggiero, A.; Neuse, J.; Vyas, M. (2005)
      Forumla chem. . A variety of 5-chloro-2(H)-1,4-oxazin-2-ones bearing a range of substituents at their 3- and 6-positions undergo Diels-Alder cycloaddition as a 2-azadiene component with electron-rich, electron-deficient, and electron-neutral dienophiles. These reactions proceed with moderate regio- and stereoselectivity to afford relatively stable and readily isolable bridged bicyclic lactone cycloadducts. Chemical manipulation of these cycloadducts affords highly substituted and functionally rich piperidines. The regio- and stereochemical preferences of the cycloadditions of 5-chloro-2(H)-1,4-oxazin-2-ones are investigated computationally using density functional theory (B3LYP/6-31G*).
    • Investigation of the effects of lamotrigine and clozapine in improving reversal-learning impairments induced by acute phencyclidine and D-amphetamine in the rat.

      Idris, Nagi F.; Repeto, P.; Neill, Joanna C.; Large, C.H. (Springer Berlin / Heidelberg, 2005)
      Rationale Phencyclidine (PCP), a glutamate/N-methyl-d-aspartate (NMDA) receptor antagonist, has been shown to induce a range of symptoms similar to those of patients with schizophrenia, while d-amphetamine induces predominantly positive symptoms. Previous studies in our laboratory have shown that PCP can selectively impair the performance of an operant reversal-learning task in the rat. Furthermore, we found that the novel antipsychotic ziprasidone, but not the classical antipsychotic haloperidol, could prevent the PCP-induced deficit. Objectives The aim of the present study was to validate the model further using the atypical antipsychotic clozapine and then to investigate the effects of lamotrigine, a broad-spectrum anticonvulsant that is known to reduce glutamate release in vitro and is able to prevent ketamine-induced psychotic symptoms in healthy human volunteers. A further aim was to compare effects of PCP and d-amphetamine in the test and investigate the effects of the typical antipsychotic haloperidol against the latter. Methods Female hooded-Lister rats were food deprived and trained to respond for food in a reversal-learning paradigm. Results PCP at 1.5 mg/kg and 2.0 mg/kg and d-amphetamine at 0.5 mg/kg significantly and selectively impaired performance in the reversal phase of the task. The cognitive deficit induced by 1.5 mg/kg PCP was attenuated by prior administration of lamotrigine (20 mg/kg and 30 mg/kg) or clozapine (5 mg/kg), but not haloperidol (0.05 mg/kg). In direct contrast, haloperidol (0.05 mg/kg), but not lamotrigine (25 mg/kg) or clozapine (5 mg/kg), prevented a similar cognitive impairment produced by d-amphetamine (0.5 mg/kg). Conclusions Our findings provide further data to support the use of PCP-induced disruption of reversal learning in rodents to investigate novel antipsychotic drugs. The results also provide evidence for different mechanisms of PCP and d-amphetamine-induced disruption of performance in the test, and their different sensitivities to typical and atypical antipsychotic drugs.
    • Investigation of the nutraceutical potential of monofloral Indian mustard bee pollen

      Ketkar, S.S.; Rathore, A.S.; Lohidasan, S.; Rao, L.; Paradkar, Anant R.; Mahadik, K.R. (2014)
      This study was designed to investigate the nutraceutical potential of monofloral Indian mustard bee pollen (MIMBP). MThe nutritional value of MIMBP was examined in terms of proteins, fats, carbohydrates, and energy value. Its chemical composition in terms of total polyphenol and flavonoid content was determined. MIMBP was screened for free flavonoid aglycones by developing and validating a high-performance liquid chromatography-photo diode array (HPLC-PDA) method. MIMBP was analyzed for in vitro antioxidant effect in terms of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging activity. MIMBP was found to be comprised of proteins ((182.2+/-5.9) g/kg), fats ((137.7+/-6.8) g/kg) and carbohydrates ((560.6+/-17.4) g/kg), which result in its high energy value ((17 616.7+/-78.6) kJ/kg). MIMBP was found to contain polyphenols ((18 286.1+/-374.0) mg gallic acid equivalent/kg) and flavonoids ((1 223.5+/-53.1) mg quercetin equivalent/kg). The HPLC-PDA analysis revealed the presence of kaempferol ((65.4+/-0.5) mg/kg) and quercetin ((51.4+/-0.4) mg/kg) in MIMBP, which can be used as markers for determining the quality of bee pollen. The MIMBP extract showed DPPH free radical-scavenging activity with a half maximal inhibitory concentration of 54.79 mug/mL. The MIMBP was found to be a rich source of nutrients providing high caloric value, which makes it a candidate for a potential nutraceutical agent. The study also illustrated the high antioxidant content of MIMBP, especially in the principle polyphenols and flavonoids, which suggests its potential role in the prevention of free radical-implicated diseases. The DPPH-scavenging effect of MIMBP further confirmed its antioxidant potential. Additionally, we developed a simple, specific and accurate HPLC-PDA method for the identification and quantification of free flavonoid aglycones. This can be applied in future screenings of the quality of pollen collected by honeybees.
    • An investigation of the origins of cattle and aurochs deposited in the Early Bronze Age barrows at Gayhurst and Irthlingborough

      Towers, Jacqueline R.; Montgomery, Janet; Evans, J.; Jay, Mandy; Parker Pearson, M. (2010-03)
      The Early Bronze Age round barrows at Irthlingborough, Northamptonshire and Gayhurst, Buckinghamshire contained remarkably large quantities of cattle (Bos taurus) remains. At Irthlingborough, at least 185 skulls with smaller numbers of mandibles, shoulder blades and pelves were found together with a small number of skeletal elements from aurochs (Bos primigenius). In contrast, the remains from Gayhurst are dominated by the limb bones from more than 300 animals. This study employed strontium isotope ratio analysis of cattle tooth enamel from 15 cattle and one aurochs to investigate the diversity of the animals’ origins at both sites and provide insights into Early Bronze Age funerary practices. Although strontium results show that most of the cattle and the aurochs included in this study were consistent with local origins, one animal from each barrow was born remotely, most likely in western Britain. In addition, a second Gayhurst animal was consistent with origins in a region of chalk rather than the local Jurassic sediments.
    • Investigation of the role of VHL-HIF signaling in DNA repair and apoptosis in zebrafish

      Kim, H.R.; Santhakumar, K.; Markham, E.; Baldera, D.; Greenald, D.; Bryant, H.E.; El-Khamisy, Sherif F.; van Eeden, F.J. (2020-03)
      pVHL is a tumor suppressor. The lack of its function leads to various tumors, among which ccRCC (clear cell renal cell carcinoma) has the most serious outcome due to its resistance to chemotherapies and radiotherapies. Although HIF promotes the progression of ccRCC, the precise mechanism by which the loss of VHL leads to tumor initiation remains unclear. We exploited two zebrafish vhl mutants, vhl and vll, and Tg(phd3:: EGFP)i144 fish to identify crucial functions of Vhl in tumor initiation. Through the mutant analysis, we found that the role of pVHL in DNA repair is conserved in zebrafish Vll. Interestingly, we also discovered that Hif activation strongly suppressed genotoxic stress induced DNA repair defects and apoptosis in vll and brca2 mutants and in embryos lacking ATM activity. These results suggest the potential of HIF as a clinical modulator that can protect cells from accumulating DNA damage and apoptosis which can lead to cancers and neurodegenerative disorders.
    • Investigations on Sanday. Vol 2. Tofts Ness: An island landscape through 3000 years of Prehistory Orcadian

      Dockrill, Stephen J.; Bond, Julie M.; Nicholson, R.A.; Smith, A.N. (2007)
      Tofts Ness is a peninsula at the north end of the Orcadian island of Sanday where mounds and banks represent a domestic landscape, marginal even in island terms, together with a funerary landscape. A combination of selective excavation and geophysical survey during 1985-8 revealed settlement and cultivation spanning Neolithic to Early Iron Age times, including burnt mounds and traces of plough cultivation. The Neolithic inhabitants of Tofts Ness appear not to have used either Grooved Ware or Unstan Ware, and it is suggested that this reflects a lack of status compared to the settlement at Pool. Instead, the pottery shares important links to contemporary assemblages from West Mainland Shetland, and this is echoed by the steatite artefacts. The link with Shetland remains visible into the Late Bronze Age. The upper levels of the main settlement mound contained the remains of stone-built roundhouses of the Late Bronze Age and Early Iron Age, of which the last survived to a height of 1.5m. A lack of personal items amongst the artefact assemblage again indicates the low status of the inhabitants. The economic evidence for all periods shows a mixed subsistence economy based on animal husbandry and barley cultivation, together with fishing, fowling and the exploitation of wild plants both terrestrial and marine. Important studies on the farming methods employed on Tofts Ness reveal a manuring strategy in managing small fields that was more akin to intensive gardening than field cultivation and a deliberate policy of harvesting the barley crop whilst under-ripe.
    • Inward rectifier potassium current (IK1) and Kir2 composition of the zebrafish (Danio rerio) heart

      Hassinen, M.; Haverinen, J.; Hardy, Matthew E.; Sheils, H.A.; Vornanen, M. (2015-12)
      Electrophysiological properties and molecular background of the zebrafish (Danio rerio) cardiac inward rectifier current (IK1) were examined. Ventricular myocytes of zebrafish have a robust (−6.7±1.2 pA pF−1 at −120 mV) strongly rectifying and Ba2+-sensitive (IC50=3.8 μM) IK1. Transcripts of six Kir2 channels (drKir2.1a, drKir2.1b, drKir2.2a, drKir2.2b, drKir2.3, and drKir2.4) were expressed in the zebrafish heart. drKir2.4 and drKir2.2a were the dominant isoforms in both the ventricle (92.9±1.5 and 6.3±1.5 %) and the atrium (28.9±2.9 and 64.7±3.0 %). The remaining four channels comprised together less than 1 and 7 % of the total transcripts in ventricle and atrium, respectively. The four main gene products (drKir2.1a, drKir2.2a, drKir2.2b, drKir2.4) were cloned, sequenced, and expressed in HEK cells for electrophysiological characterization. drKir2.1a was the most weakly rectifying (passed more outward current) and drKir2.2b the most strongly rectifying (passed less outward current) channel, whilst drKir2.2a and drKir2.4 were intermediate between the two. In regard to sensitivity to Ba2+ block, drKir2.4 was the most sensitive (IC50=1.8 μM) and drKir2.1a the least sensitive channel (IC50=132 μM). These findings indicate that the Kir2 isoform composition of the zebrafish heart markedly differs from that of mammalian hearts. Furthermore orthologous Kir2 channels (Kir2.1 and Kir2.4) of zebrafish and mammals show striking differences in Ba2+- sensitivity. Structural and functional differences needs to be taken into account when zebrafish is used as a model for human cardiac electrophysiology, cardiac diseases, and in screening cardioactive substances.
    • Ion microprobe assessment of the heterogeneity of Mg/Ca, Sr/Ca and Mn/Ca ratios in Pecten maximus and Mytilus edulis (bivalvia) shell calcite precipitated at constant temperature.

      Clarke, Leon J.; Kennedy, H.A.; Richardson, C.A.; Freitas, P.S. (2009)
      Small-scale heterogeneity of biogenic carbonate elemental composition can be a significant source of error in the accurate use of element/Ca ratios as geochemical proxies. In this study ion microprobe (SIMS) profiles showed significant small-scale variability of Mg/Ca, Sr/Ca and Mn/Ca ratios in new shell calcite of the marine bivalves Pecten maximus and Mytilus edulis that was precipitated during a constant-temperature culturing experiment. Elevated Mg/Ca, Sr/Ca and Mn/Ca ratios were found to be associated with the deposition of elaborate shell features, i.e. a shell surface stria in P. maximus and surface shell disturbance marks in both species, the latter a common occurrence in bivalve shells. In both species the observed small-scale elemental heterogeneity most likely was not controlled by variable transport of ions to the extra-pallial fluid, but by factors such as the influence of shell organic content and/or crystal size and orientation, the latter reflecting conditions at the shell crystalsolution interface. In the mid and innermost regions of the P. maximus shell the lack of significant small-scale variation of Mg/Ca ratios, which is consistent with growth at constant temperature, suggest a potential application as a palaeotemperature proxy. Cross-growth band element/Ca ratio profiles in the interior of bivalve shells may provide more promising palaeo-environmental tools than sampling from the outer region of bivalve shells.
    • The ionic liquid ethyltri-n-butylphosphonium tosylate as solvent for the acid-catalysed hetero-Michael reaction.

      Karodia, Nazira; Liu, Xihan; Ludley, Petra; Pletsas, Dimitrios; Stevenson, Grace (2006)
      A new and convenient method for the acid-catalysed Michael addition reactions of alcohols, thiols and amines to methyl vinyl ketone has been developed using the ionic liquid ethyltri-n-butylphosphonium tosylate. The reaction conditions are mild and obviate the need for toxic and expensive Lewis acid catalysts, offering advantages over more commonly used systems.
    • Iontophoretic estradiol skin delivery and tritium exchange in ultradeformable liposomes

      Bonner, Michael C.; Barry, Brian W.; Essa, Ebtessam A. (2002)
      This work evaluated the in vitro transdermal iontophoretic delivery of tritiated estradiol from ultradeformable liposomes compared with saturated aqueous solution (control). Effects of current density and application time on tritium exchange with water were also determined. Penetration studies used three Protocols. Protocol I involved occluded passive steady state estradiol penetration from ultradeformable liposomes and control. The effect of current densities on drug penetration rates was also assessed (Protocol II). In Protocol III, three consecutive stages of drug penetration (first passive, iontophoresis and second passive) through the same human epidermal membranes were monitored. Such an experimental design investigated the possible effect of high current density (0.8 mA/cm2) on skin integrity. The tritium exchange study showed that extent of exchange correlated well with current density and time of application, with some shielding of estradiol by the liposomal structure. Liposomes enhanced estradiol passive penetration after occlusion. Protocol II showed that estradiol flux increased linearly with current density, although being delivered against electroosmotic flow. In Protocol III, reduction in flux of the second passive stage to near that of the first reflected a reversibility of the structural changes induced in skin by current.
    • Irish-Scottish connections in the 1st millennium AD: an evaluation of the links between souterrain ware and Hebridean ceramics

      Armit, Ian (2008)
      Although some limited consideration has been given to the possibility of links between the early medieval ceramic traditions of the Western Isles and the souterrain ware of north-east Ireland, these have tended to be framed in the context of supposed Dalriadic cultural infl uence fl owing from Ireland to Scotland. A re-evaluation of the possible relationships between these pottery styles suggests that souterrain ware might instead be seen as part of a regional expansion of western Scottish pottery styles in the seventh¿eighth centuries AD. This raises the question of what social processes might underlie the cross-regional patterning evident in what remains a vernacular, rather than a high-status, technology.
    • Is it assessment of learning or assessment for learning?

      Rahman, Sayeeda; Majumder, Md A.A. (2014)
      Assessment is a central feature of teaching and the curriculum. It powerfully frames how students learn and what students achieve. It is one of the most significant influences on students’ experience of higher education and all that they gain from it. The reason for an explicit focus on improving assessment practice is the huge impact it has on the quality of learning’.1 ‘Students should realize that assessment can be an opportunity for learning, rather than just something to be endured and suffered’.2 'Institutions should ensure that appropriate feedback is provided to students on assessed work in a way that promotes learning and facilitates improvement'.3
    • Is the ability to identify deviations in multiple trajectories compromised by amblyopia?

      Tripathy, Srimant P.; Levi, D.M. (2006)
      Amblyopia results in a severe loss of positional information and in the ability to accurately enumerate objects (V. Sharma, D. M. Levi, & S. A. Klein, 2000). In this study, we asked whether amblyopia also disrupts the ability to track a near-threshold change in the trajectory of a single target amongst multiple similar potential targets. In the first experiment, we examined the precision for detecting a deviation in the linear motion trajectory of a dot by measuring deviation thresholds as a function of the number of moving trajectories (T). As in normal observers, we found that in both eyes of amblyopes, threshold increases steeply as T increases from 1 to 4. Surprisingly, for T = 1-4, thresholds were essentially identical in both eyes of the amblyopes and were similar to those of normal observers. In a second experiment, we measured the precision for detecting a deviation in the orientation of a static, bilinear "trajectory" by again measuring deviation thresholds (i.e., angle discrimination) as a function of the number of oriented line "trajectories" (T). Relative to the nonamblyopic eye, amblyopes show a marked threshold elevation for a static target when T = 1. However, thresholds increased with T with approximately the same slope as in their preferred eye and in the eyes of the normal controls. We conclude that while amblyopia disrupts static angle discrimination, amblyopic dynamic deviation detection thresholds are normal or very nearly so.
    • Is there a link between dizziness and vision? A systematic review

      Armstrong, Deborah; Charlesworth, Emily; Alderson, Alison J.; Elliott, David B. (2016-07)
      Purpose: The aim of this study was to systematically review the literature to investigate the link (if any) between vision and dizziness. Methods: Medline, CINAHL, AMED, Web of Science and The Cochrane Library were searched with keywords chosen to find articles which investigated the causes of dizziness and considered vision as a possible trigger. Citation chaining of all included papers was performed in addition to the hand searching of all reference lists. Unpublished literature was identified using www.opengrey.eu. The review considered studies involving adults which link, measure or attempt to improve any aspect of vision in relation to dizziness. Results: Nine thousand six hundred and eighty one possible references were found, and the abstracts were screened independently by two reviewers to determine if they should be included in the study. Thirteen papers were found which investigated whether dizziness was linked to an assessment of vision. Visual impairment measures were crude and typically self-report, or Snellen visual acuity with little or no measurement details. Five studies found an independent link between dizziness and vision, five found a weak association (typically finding a link when univariate analyses were used, but not when multivariate analyses were used), and three found no association. Studies finding a strong link were usually cross-sectional with a large study population whereas those finding a weak association had relatively small numbers of participants. Studies which did not find an association used a broad definition of dizziness that included the term light-headedness, an unreliable Rosenbaum near visual acuity chart or an unusual categorisation of visual acuity. Conclusions: This review suggests that dizziness (although likely not ‘light-headedness’) is linked with poor vision although further studies using more appropriate measures of vision are recommended.
    • Ischaemic skeletal muscle increases serum ischaemia modified albumin.

      Troxler, M.; Thompson, D.; Homer-Vanniasinkam, Shervanthi (2009-11-02)
      Objectives Ischaemia modified albumin (IMA) has been used as a marker of myocardial ischaemia but little is known about its production during ischaemia of other tissues. The clinical models of patients with intermittent claudication and major arterial surgery were used to investigate IMA production from ischaemic skeletal muscle. Materials and methods IMA was measured pre-operatively, at end ischaemia, and 5min, 4, 24, 48, 72 and 144h post-surgery in patients undergoing (a) revascularisation for intermittent claudication (IC, n=15), (b) abdominal aortic aneurysm repair (AAA, n=12) and controls (n=16). Results The median pre-operative IMA concentration in IC patients was significantly higher than the AAA group (88.3 versus 83.5U/ml, p=0.036) and controls (88.3 versus 80.3U/ml, p=0.031). IMA concentrations increased significantly during arterial clamping in both IC and AAA groups (88.3 versus 120.0U/ml, p=0.001; 83.5 versus 118.8U/ml, p=0.002, respectively) consistent with increased skeletal muscle ischaemia. In contrast, there was only a mild perioperative increase in the controls (80.3 versus 91.6U/ml, p=0.012). Conclusions Patients with intermittent claudication have significantly elevated IMA and skeletal muscle ischaemia during arterial surgery results in significantly increased circulating IMA. When IMA is used to detect myocardial ischaemia, ischaemic skeletal muscle must be excluded.
    • Isolation of stimulus characteristics contributing to Weber's law for position.

      Whitaker, David J.; Bradley, A.; Barrett, Brendan T.; McGraw, Paul V. (2002)
      To examine the independent contribution of various stimulus characteristics to positional judgements, we measured vernier alignment performance for three types of Gabor stimuli. In one, only the contrast envelope of the upper and lower stimulus elements was offset, with the luminance-modulated carrier grating remaining in alignment. In the second, only the carrier grating was offset. In the third, both carrier and envelope were offset together. Performance was examined over a range of element separations. When both cues are available, thresholds for small separations are dominated by carrier offset information and are inversely proportional to carrier frequency. At large separations, thresholds are governed by the spatial scale characteristics of the envelope. For broad-band stimuli such as lines, bars or dots typically used for vernier acuity, their higher frequency content can be used when separations are small, but as separation increases a smooth transition between the scales that determine threshold results in the continuum known as Weber's law for position. That is, with increasing separation, larger scales must be used, and thresholds increase in direct proportion to 1/frequency.
    • Isolation rearing impairs novel object recognition and attentional set shifting performance in female rats

      McLean, Samantha L.; Grayson, Ben; Harris, M.; Protheroe, C.; Bate, S.; Woolley, M.L.; Neill, Joanna C. (2010-01)
      It has been suggested that the isolation rearing paradigm models certain aspects of schizophrenia symptomatology. This study aimed to investigate whether isolation rearing impairs rats’ performance in two models of cognition: the novel object recognition (NOR) and attentional set-shifting tasks, tests of episodic memory and executive function, respectively. Two cohorts of female Hooded-Lister rats were used in these experiments. Animals were housed in social isolation or in groups of five from weaning, post-natal day 28. The first cohort was tested in the NOR test with inter-trial intervals (ITIs) of 1 min up to 6 h. The second cohort was trained and tested in the attentional set-shifting task. In the NOR test, isolates were only able to discriminate between the novel and familiar objects up to 1-h ITI, whereas socially reared animals remembered the familiar object up to a 4-h ITI. In the attentional set-shifting task, isolates were significantly and selectively impaired in the extra-dimensional shift phase of the task (P < 0.01). Rats reared in isolation show impaired episodic memory in the NOR task and reduced ability to shift attention between stimulus dimensions in the attentional set-shifting task. Because schizophrenic patients show similar deficits in performance in these cognitive domains, these data further support isolation rearing as a putative preclinical model of the cognitive deficits associated with schizophrenia.
    • Isomorphism: 'Molecular similarity to crystal structure similarity' in multicomponent forms of analgesic drugs tolfenamic and mefenamic acid

      Ranjan, S.; Devarapalli, R.; Kundu, S.; Saha, S.; Deolka, S.; Vangala, Venu R.; Reddy, C.M. (2020-03)
      The non-steroidal anti-inflammatory drugs mefenamic acid (MFA) and tolfenamic acid (TFA) have a close resemblance in their molecular scaffold, whereby a methyl group in MFA is substituted by a chloro group in TFA. The present study demonstrates the isomorphous nature of these compounds in a series of their multicomponent solids. Furthermore, the unique nature of MFA and TFA has been demonstrated while excavating their alternate solid forms in that, by varying the drug (MFA or TFA) to coformer [4-dimethylaminopyridine (DMAP)] stoichiometric ratio, both drugs have produced three different types of multicomponent crystals, viz. salt (1:1; API to coformer ratio), salt hydrate (1:1:1) and cocrystal salt (2:1). Interestingly, as anticipated from the close similarity of TFA and MFA structures, these multicomponent solids have shown an isomorphous relation. A thorough characterization and structural investigation of the new multicomponent forms of MFA and TFA revealed their similarity in terms of space group and structural packing with isomorphic nature among the pairs. Herein, the experimental results are generalized in a broader perspective for predictably identifying any possible new forms of comparable compounds by mapping their crystal structure landscapes. The utility of such an approach is evident from the identification of polymorph VI of TFA from hetero-seeding with isomorphous MFA form I from acetone–methanol (1:1) solution. That aside, a pseudopolymorph of TFA with dimethylformamide (DMF) was obtained, which also has some structural similarity to that of the solvate MFA:DMF. These new isostructural pairs are discussed in the context of solid form screening using structural landscape similarity