Search

Mandibular third molar is the most common tooth to become impacted. Mandibular third molars may acquire a range of patterns and positions and may lead to a diverse group of pathologies. The objective of this study was to enlist the different patterns of mandibular third molar impactions and their associated pathologies. This descriptive study was carried out at Oral and Maxillofacial Surgery Unit of Lahore Medical & Dental College, Lahore from February 2014 to September 2015. A total of 271 patients with 382 impacted mandibular third molars were included in the current study. Their ages were between 20 to 53 years (Mean±SD, 27.81±7.37). 114 (42.07%) were male and 157 (57.93%) females with male to female ratio of 1:1.38. Patients were evaluated with thorough history, clinical and radiographic examination. Periapical and panoramic radiographs were used to assess the pattern of mandibular third molar impactions and their associated pathologies. Mesioangular angulation (45.55%) with class II ramus relation (60.73%) and Position A (54.71%) depth was the most frequent pattern of impaction. A total of 324 pathologies were seen in 271 patients who presented for removal of impacted mandibular third molars. The most common pathology associated with the impacted mandibular third molar was dental caries of third molar (38.89%), followed by pericoronitis (29.01%, periodontal disease (14.19%) and a low frequency of cysts and tumors (3.39%). Prophylactic removal of impacted mandibular third molar with unfavorable patterns and positions may be beneficial for the patients to prevent the patients from associated pathologies. [ABSTRACT FROM AUTHOR]

In the present research work comparative investigation for decolorisation of textile effluents by different chemical methods was investigated. One industrial effluent was prepared synthetically and other two were collected from industry. Samples were subjected to three different advance oxidation processes which were Fenton and photo-Fenton. Fenton treatment was optimised with different parameters like concentration of H2O2, pH, dose of Fe2+ and temperature. Then optimised conditions were employed with varying light intensities in photo-Fenton treatment using UV/vis. lamp and at different time intervals of day in solar-Fenton treatment using solar light. The effectiveness was evaluated by water quality assurance parameters such as total organic carbon (TOC), chemical oxygen demand (COD) and total suspended solids (TSS). The maximum decolorisation and mineralisation was obtained with photo-Fenton treatment using UV/Visible lamp which is supported by showing decreases in chemical oxygen demand (COD) and total organic carbon (TOC) of the treated effluents solutions. The Ames mutagenicity testing assay showed reduced mutagenicity of treated effluents by all three treatment technologies in both strains of Salmonella (TA98 and TA100). The results showed the employment studied treatments led to decolorisation and substantial mineralisation of effluents under study, however, photo-Fenton process exhibited a little more oxidation potential than others. [ABSTRACT FROM AUTHOR]

The Collum angle or the cephalometric crown-root angulation of permanent maxillary central incisors is an angle formed between the long axes of the crown and root of upper central incisors. This study aimed to evaluate the Collum angle in patients with Class II division 1 and 2 malocclusions for identifying the nature of differences, if any. Out of a total of 565 lateral cephalograms available at Lahore Medical and Dental College Orthodontic department during 2013-2014, 60 satisfied the inclusion criteria and 30 each were selected for the two malocclusion groups. The Collum angle of the permanent maxillary central incisors differ significantly among Class II division 1 and 2 permanent maxillary central incisor and showed pronounced axial bending in division 2 incisors (10.03° ± 4.37°) as compared to division 1 (3.65° ± 3.79°). The mean difference between both groups was 6.38° + 5.81°. This feature could possibly contribute to the development of a deep overbite in Class II division 2 malocclusion and also may limit the amount of root torque during fixed appliance therapy. [ABSTRACT FROM AUTHOR]

This survey was conducted to study the levels of confidence in performing basic dental procedures, reported by graduates of three different dental colleges of Lahore. A Sample of 180 students was surveyed through specially designed proformas, using five points Likert's Scale. A total response rate of 90.5 % was achieved. The null hypothesis was that graduates from different institutions have equal levels of confidence. Analysis of variance was used to assess difference of scores among institutions. P value pf 0.05 was considered to be significant. Statistically significant differences among institutions were noted(p=2.44). Students were most confident in simpler procedures in which they had had most clinical experience. They were least confident in more complex procedures in which they had the least clinical experience during third and final year of BDS. Increased clinical time in complex procedures may help in increasing graduating students' confidence procedures highlighted in this study. [ABSTRACT FROM AUTHOR]

Radicular cysts are the most common odontogenic cysts of inflammatory origin affecting the human jaws. Radicular cysts are usually asymptomatic but can result in slow growth tumefaction and involve many adjacent sound teeth endangering their vitality and prognosis. The objectives of this study were to enumerate and evaluate the etiological factors and the pattern of presentation of radicular cysts in a tertiary care centre in Pakistan. A total of 58 patients were included in this case series study after taking history, clinical examination, radiological findings, aspiration test and histological diagnosis of lesion by biopsy report. It was carried out at the Oral and Maxillofacial Surgery Department, Lahore Medical and Dental College, Lahore from April 2012 to August 2014. The patients in the study included 30 male (51.72%) and 28 female (48.28%). Most cases were diagnosed in the second decade of life (50.00%) which declined in the later age groups. The most affected region was the anterior maxilla (65.52%, n=38), followed by anterior mandible (18.96%, n=11). The main etiological factor was dental trauma followed by unrestored nonvital carious teeth. Radicular cyst is the most commonly occurring odontogenic cyst which affects the maxillofacial skeleton with varying frequency. A proper early screening of dental trauma can significantly reduce the incidence of some of these cystic lesions. In addition, patient education with regards to improved oral health and regular dental check ups is important for reducing the caries prevalence in the population. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the effect of marginal flap and paramarginal flap designs on maximum mouth opening following surgical removal of impacted mandibular third molars. This comparative study consisted of sixty patients which were divided into two groups of thirty each and was carried out at Oral and Maxillofacial Department, Lahore Medical and Dental College, Lahore from June 2012 to October 2013. Maximum mouth opening was recorded preoperatively. A marginal flap was used in one randomly chosen half of the patient's sample, and a paramarginal flap was used in the other half. The effect of these flaps on maximum mouth opening was studied postoperatively. No significant difference was found between marginal and paramarginal flaps on maximum mouth opening at second and seventh days after surgical removal of impacted mandibular third molar (P>0.05). Therefore, the decision to use a marginal flap or a paramarginal flap may be based on surgeon's preference. [ABSTRACT FROM AUTHOR]

The aim of this research was to study the evolution of dental health of dental students during their academic training and to assess the extent to which the knowledge acquired was reflected in their own dental care. A cross sectional survey was carried out in a Dental College of Lahore. The sample was selected randomly choosing 40 students from each year with an age range between 18 and 24 years. The data for this study were collected using a pre-tested self- administered questionnaire and was considered mandatory for all participants to fill out. All participants were clinically examined. Their oral cavity was thoroughly checked for any ongoing disease process and a DMFT chart was filled accordingly. Data entry and analysis was done using the IBM SPSS version 20. Final sample size was 160 (Females: 75.6% / males: 24.4%). The highest frequency of females and males was observed in 3rd year and 1st year respectively Frequency distribution and Chi-Square tests of significance were performed. High levels of DMF were not that evident. Almost 30% (48) students had .00 DMF and 23% (37) had 1.00 DMF (p<0.05). Only a small number of students were found using non-fluoridated toothpaste (p< 0.01). Chi-square Analysis revealed a significant relations between the year of study and DMFT of the students (p<0.05) along with Gender and age as well as year of study and age (p<0.01). [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the correlation of hypodontia in orthodontic patients with third molar agenesis and to compare them with patients without third molar agenesis. A sample of 270 patients between age group of 12-35 years was selected from the records of Orthodontic Department of Dental College, LMDC. Panoramic radiographs and dental casts were used to determine the frequency of hypodontia. The teeth that were found missing were maxillary lateral incisor (3.1%), followed by mandibular lateral incisors (2.6%), mandibular central incisors (1.8%) and mandibular second premolars (0.55%). The Pearson chi-square test was used to determine the correlation between third molar agenesis and agenesis of other teeth. A significant correlation was established between third molar agenesis and reduced number of other teeth statistically. (p<0.05). [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the efficacy of interpositional temporalis fascia flap in the management of TMJ ankylosis by assessing the maximal mouth opening prior and after the procedure and prevention of re-ankylosis after interpositioning. This case series study consisted of twenty one patients of TMJ ankylosis, unilateral or bilateral, irrespective of age and gender. It was carried out at the Oral & Maxillofacial Surgery Department, Lahore Medical & Dental College, Lahore from December 2010 to September 2013. OPG and 3-D scan were the standard radiographs and were taken in every case. All the patients were treated surgically by temporalis fascia flap interpositional arthroplasty. Inter-incisal distance (IID) / mouth opening were recorded preoperatively, immediately after completion of operation and postoperatively at follow-up. An inter-incisal distance/ mouth opening of at least 35mm was achieved in all cases and showed no recurrence of ankylosis in any of the patients. Interpositional arthroplasty using temporalis fascia flap is an effective and reliable method to prevent re-ankylosis. Temporalis fascia flap is available at the operative site, easy to raise, well vascularized, reliable and shows better long term results. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the outcome of management of mandibular third molar impaction in terms of wound healing and periodontal probing depth of the adjacent second molar in patients treated by marginal flap versus paramarginal flap. This quasi experimental study consisted of sixty patients divided into two groups of thirty each (ages 18 to 30 years), who required surgical removal of impacted mandibular third molars. Periodontal probing depth of the adjacent second molar was recorded preoperatively. A marginal flap was used in one randomly chosen half of the patient's sample, and a paramarginal flap was used in the other half. The influence of these flaps on wound healing and periodontal probing depth of the adjacent second molar was studied postoperatively. No wound dehiscence occurred with the use of marginal flap or the paramarginal flap at 1 and 2 weeks after surgery (P>0.05). The buccal and distal probing depths of the adjacent second molar showed no significant difference between marginal flap and paramarginal flap before surgery and at 2 weeks and 4 weeks after surgery (P>0.05). No significant difference was found with the use of paramarginal flap instead of traditional marginal flap in the removal of impacted mandibular third molar. [ABSTRACT FROM AUTHOR]

This study was aimed at assessing the various factors associated with shisha smoking such as attitudes, practice and addiction among the adult population aged 15 - 44 years in Lahore city. A cross-sectional survey was held in Shisha bars, tobacco shops and Shisha cafes along with some major undergraduate colleges and Universities of Lahore in summer of 2013. All adults aged between 15 and 44 years of age who consumed Shisha were included in the sample. All other age groups and people not smoking were excluded. The data for this study were collected with the participants using an approved self- administered questionnaire. Data analysis was done using the IBM SPSS version 20. The final sample size was 300 (male 194 and female 106). The largest group was of young adults aged 21-25 years. Out of all the participants, 65% of the sample was smoking shisha for over a year. It was noteworthy that encouragement for shisha smoking was brought on more by friends (61%) as compared to colleagues (9%) and the money spent on such activities was utilized from their own pocket money (70.3%). It was also observed that 42.3% of the sample recognized water-pipe/shisha as being a stress reliever and 68.7% admitted it to be a status symbol. Hence, 77.7% of the sample smoked shisha in the company of friends with 11.3% claiming to be completely addicted to it. In addition, 72.3% of the participants of this study refused to quit water-pipe/shisha smoking. Significance was found in Pearson's correlation between gender and duration, expenditure and frequency of consumption, addiction and duration, status symbol and stress reliever, company and status symbol and addiction with duration and wanting to quit (p < 0.05). A high significance was observed in age with duration, expenditures, company, stress reliever and status symbol (p < 0.01). Frequency of consumption with addiction, and stress reliever (p < 0.01); stress reliever with age (p < 0.01); addiction with stress reliever and status symbol (p < 0.01); wanting to quit with gender and duration (p < 0.01); and lastly expenditures with encouragement, addiction, status symbol and stress reliever (p < 0.01) were also observed in 2-tailed significance of Pearson's correlation. This study concludes that shisha smoking is responsible for a lot of ill-effects in the oral cavity apart from the body itself. This habit should be minimized and the misconceptions related to it should be made clear to all young population to avoid further harm to their health. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the attitudes of dental surgeons towards posterior composite restorations in terms of case selection and concerns. 100 questionnaires were randomly distributed to the dental surgeons working in hospitals and clinics in Lahore. The questionnaires were designed to elicit information regarding case selection criteria and main concerns while placing posterior composite restorations. 92 completed questionnaires were returned. 58 general dental practitioners and 34 specialists responded to the questionnaire. 81.5% of the dentists preferred composites for restoring only small defects. 46.5% selected composites for posterior restoration on patient demand. Conservation of tooth structure was the cause for placing 81.5%, esthetics for 67.4% and patient preference for placing 74% restoration by these dentists. 69.5% of the dentists reported to adopt methods to maintain isolation during composite placement, 60% showed concern about contact point generation and 32.6% adopted techniques to minimize polymerization shrinkage stresses. Differences in responses were not remarkable between general dentist group and specialist groups. Conclusion: Conservation of tooth structure and esthetics were the main reasons for selection of posterior composites. Posterior composite restorations were chosen mainly for small defects. Patient preference was given weightage for material selection. [ABSTRACT FROM AUTHOR]

An investigation was carried out to assess the dental health awareness amongst school children aged 5 to 10 years in the city of Lahore, Pakistan. This cross-sectional survey included nine different schools of Lahore City having a total sample size of 573. The assessment of the children's level of awareness was done by clinical examination of their teeth followed by an interview. One dentist carried out all dental examinations. The examiner recorded caries incidence in all erupted teeth. Following the clinical examination, children participated in an interview using a questionnaire. The questionnaire included information about gender, age, family structure, and information regarding tooth brushing habits, routine, knowledge about brushing, amount of tooth paste used, who taught them about brushing and visits to the dentist. Data analysis was done using SPSS version 19.0 and included descriptive statistics which was frequency distribution and cross-tabulation. It was found that teachers had played a very little role in educating the children about tooth brushing and providing dental awareness (6.8%). It was the parents, however, who brought about more dental awareness in their children and gave them the necessary knowledge about oral hygiene (36.1%) especially male children. This association was highly statistically significant (p= 0.001). Majority of the children used half-length of toothpaste for tooth brushing and this frequency increased in 8 year olds therefore reducing their decayed missing filled teeth index score to a 0.31 as compared to 9 year olds (0.71). A statistically significant association was also seen between age and toothpaste size (p= 0.003) [ABSTRACT FROM AUTHOR]

The objectives of this study were to assess the Oral Health-Related Quality of Life (OHRQoL) among students in a private Dental Undergraduate School in Lahore. A cross sectional study design was used. One hundred and twenty dental students of years 2 and 3 returned completed forms containing the 14 item Oral Health Impact Profile (OHIP-14). Old and new batch students of both years were included giving a sum to four batches of students. Data analysis was done using IBM SPSS version 19. The results showed the perceived OHRQoL among students studying in two different stages (year 2 and 3) of the dental course. Age was found to be significant (P < 0.05) with the OHRQoL dimension of 'Physical pain: discomfort eating food' (p=0.043) and highly significant (P < 0.01) with the dimensions of 'Physical discomfort: poor diet' (p=0.007), 'Psychological Discomfort: Selfconsciousness' (p=0.004), 'Functional Limitation: worsened taste' (p=0.007), 'Handicap' (p=0.001) and 'Psychological disability: embarrassment' (p=0.001). Gender was found to be significant with 'Psychological disability: embarrassment' (p=0.046) and 'Social disability: difficulty in doing job' (p=0.040) and was highly significant with 'Psychological Discomfort: Self-consciousness' (p=0.001), 'Functional Limitation: trouble pronouncing words' (p=0.002) and 'Social disability: irritability' (p=0.010). Year of study showed high significance with Psychological discomfort: self-consciousness (p=0.002) The results of this study underscored the relationship between the OHRQoL and age, gender and study year and their impact on OHRQoL among the dental student community. It is essential that students are enlightened with oral health problems and how to overcome them, so that subsequent years of study in a Dental School and the OHRQoL are least affected. [ABSTRACT FROM AUTHOR]

This study was aimed to assess the Oral Health-Related Quality of Life (OHRQoL) among aged 40-70 years. The survey was conducted in Prosthodontics department of a private Dental College in Lahore, Pakistan. A cross sectional survey was carried out over a period of three months (August-October 2010). New male and female patients aged between 40 and 70 years, who came to the department of Prosthodontics for partial and complete denture problems were included in the sample. All other age groups and old (who were undergoing treatment in the department) patients were excluded. Data for this study was collected by carrying out an interview using the Oral Health Impact Profile 14 which is the shorter version of OHIP 49. Two hundred and ten patients completed the questionnaire forms containing the 14 item Oral Health Impact Profile (OHIP-14). Data analysis was done using IBM SPSS version 19. The results showed the perceived OHRQoL among adults ranging from 40-70 years in age. Age was found to be highly significant (p < 0.01) with the OHRQoL dimension of 'psychological discomfort: feeling tense' (p=0.002) and 'physical disability: interrupted meals' (p=0.006) and significant (p < 0.05) with the dimensions of 'functional limitation: worsened taste' (p=0.04) Gender was found to be significant with 'psychological disability: difficulty relaxing' (p=0.04) and highly significant with 'social disability: irritability' (p=0.003), 'handicap: life less satisfying' (p=0.002), 'physical disability: poor diet' (p=0.01), 'handicap: inability to function' (p=0.002) and 'handicap: inability to function' (p=0.002). Complete and partial denture appliances showed significance with the dimensions of 'functional limitation: worsened taste' (p=0.02) and portrayed high significance with 'physical pain: aching in mouth' (p=0.01) and 'physical pain: discomfort eating food' (p=0.001). [ABSTRACT FROM AUTHOR]

Abstract Background The risk factors for progression of chronic kidney disease (CKD) in type 2 diabetes mellitus (DM) have not been fully elucidated. Although uncontrolled blood pressure (BP) is known to be deleterious, other factors may become more important once BP is treated. Methods All patients seen in the outpatient clinics of our hospital between January 1993 and September 2002 with type 2 DM and clinical evidence of CKD were evaluated. Progression of kidney disease was evaluated by rate of decline of glomerular filtration rate (GFR) as estimated from the simplified MDRD formula. Variables associated with progression in univariate analyses were examined by multivariate analysis to determine the factors independently associated with kidney disease progression. Results 343 patients (mean age 69 years; all male; 77% Caucasian) were studied. Mean BP, glycated hemoglobin, and serum cholesterol during the study period were 138/72 mmHg, 8.1%, and 4.8 mmol/L, respectively. Mean decline of GFR was 4.5 ml min-1 1.73 m2-1 yr-1 (range -14 to +32). Low initial serum albumin (p < 0.001), black race (p < 0.001), and degree of proteinuria (p = 0.002), but not blood pressure, glycated hemoglobin, or serum cholesterol, were independently associated with progression. Conclusion In a cohort of diabetic patients with CKD in whom mean BP was < 140/80 mmHg, the potentially remediable factors hypoalbuminemia and proteinuria but not blood pressure were independently associated with progression of kidney disease. Further understanding of the relationship between these factors and kidney disease progression may lead to beneficial therapies in such patients.

Nasolabial cyst is a relatively uncommon benign non-odontogenic type of cyst. It commonly presents in young adults and manifests as a swelling in the region of the nasolabial furrow producing a bulge beneath the nasal ala. The resultant facial disigurement and occasional pain following infection warrant a surgical treatment. Conservative enucleation via an intra-oral approach is the treatment of choice. A rare case of nasolabial cyst in an 11-year-old female child was reported. [ABSTRACT FROM AUTHOR]

The HIV transgenic (HIVtg) rat is a commonly used animal model of chronic HIV infection that exhibits a wide range of cognitive deficits. To date, relatively little work has been conducted on these rats' capacity for reversal learning, an assay of executive function and cognitive flexibility used in humans. The present study sought to determine the impact of HIV genotype on probabilistic reversal learning, effortful motivation, and spontaneous locomotion/exploration in rats. Male (n = 8) and female (n = 8) HIVtg rats and wildtype (WT) controls were utilized. Cognitive flexibility was assessed via the Probabilistic Reversal Learning Task (PRLT), which reinforced responses to two stimuli on differential probabilistic schedules that periodically reversed. Effortful motivation and locomotor/exploratory behavior were assessed via the Progressive Ratio Breakpoint Task (PRBT) and the Behavioral Pattern Monitor (BPM), respectively. Regardless of sex, HIVtg rats required fewer trials to ascertain initial PRLT reward schedules than WT rats, and completed the same number of reversals. Secondary behaviors suggested that HIVtg PRLT performance was facilitated by a speed-accuracy tradeoff strategy. No main or interactive effects of genotype were observed in the PRBT or BPM. Relative to WT controls, HIVtg rats exhibited superior probabilistic reinforcement learning. Reversal learning was unaffected by HIV genotype, as was effortful motivation and exploratory behavior. These findings contrast with previous characterizations of the HIVtg rat, thus indicating a nuanced cognitive profile that is dependent upon such task specifications as within- versus between-session assessment and probabilistic versus deterministic reward schedules., (© 2021. The Psychonomic Society, Inc.)

Background: HIV-associated neurocognitive disorder (HAND) is commonly observed in persons living with HIV (PWH) and is characterized by cognitive deficits implicating disruptions of fronto-striatal neurocircuitry. Such circuitry is also susceptible to alteration by cannabis and other drugs of abuse. PWH use cannabis at much higher rates than the general population, thus prioritizing the characterization of any interactions between HIV and cannabinoids on cognitively relevant systems. Prepulse inhibition (PPI) of the startle response, the process by which the motor response to a startling stimulus is attenuated by perception of a preceding non-startling stimulus, is an operational assay of fronto-striatal circuit integrity that is translatable across species. PPI is reduced in PWH. The HIV transgenic (HIVtg) rat model of HIV infection mimics numerous aspects of HAND, although to date the PPI deficit observed in PWH has yet to be fully recreated in animals., Methods: PPI was measured in male and female HIVtg rats and wild-type controls following acute, nonconcurrent treatment with the primary constituents of cannabis: Δ 9-tetrahydrocannabinol (THC; 1 and 3 mg/kg, s.c.) and cannabidiol (1, 10, and 30 mg/kg, i.p.)., Results: HIVtg rats exhibited a significant PPI deficit relative to wild-type controls. THC reduced PPI in controls but not HIVtg rats. Cannabidiol exerted only minor, genotype-independent effects on PPI., Conclusions: HIVtg rats exhibit a relative insensitivity to the deleterious effects of THC on the fronto-striatal function reflected by PPI, which may partially explain the higher rates of cannabis use among PWH., (© The Author(s) 2021. Published by Oxford University Press on behalf of CINP.)

The 5-HT 2A receptor is thought to be the primary target for psilocybin (4-phosphoryloxy- N , N -dimethyltryptamine) and other serotonergic hallucinogens (psychedelic drugs). Although a large amount of experimental work has been conducted to characterize the pharmacology of psilocybin and its dephosphorylated metabolite psilocin (4-hydroxy- N , N -dimethyltryptamine), there has been little systematic investigation of the structure-activity relationships (SAR) of 4-substituted tryptamine derivatives. In addition, structural analogs of psilocybin containing a 4-acetoxy group, such as 4-acetoxy- N , N -dimethyltryptamine (4-AcO-DMT), have appeared as new designer drugs, but almost nothing is known about their pharmacological effects. To address the gap of information, studies were conducted with 17 tryptamines containing a variety of symmetrical and asymmetrical N , N -dialkyl substituents and either a 4-hydroxy or 4-acetoxy group. Calcium mobilization assays were conducted to assess functional activity at human and mouse 5-HT 2 subtypes. Head-twitch response (HTR) studies were conducted in C57BL/6J mice to assess 5-HT 2A activation in vivo . All of the compounds acted as full or partial agonists at 5-HT 2 subtypes, displaying similar potencies at 5-HT 2A and 5-HT 2B receptors, but some tryptamines with bulkier N -alkyl groups had lower potency at 5-HT 2C receptors and higher 5-HT 2B receptor efficacy. In addition, O -acetylation reduced the in vitro 5-HT 2A potency of 4-hydroxy- N , N -dialkyltryptamines by about 10- to 20-fold but did not alter agonist efficacy. All of the compounds induce head twitches in mice, consistent with an LSD-like behavioral profile. In contrast to the functional data, acetylation of the 4-hydroxy group had little effect on HTR potency, suggesting that O -acetylated tryptamines may be deacetylated in vivo , acting as prodrugs. In summary, the tryptamine derivatives have psilocybin-like pharmacological properties, supporting their classification as psychedelic drugs., Competing Interests: The authors declare no competing financial interest., (© 2020 American Chemical Society.)

The ergoline d-lysergic acid diethylamide (LSD) is one of the most potent psychedelic drugs. 1-Acetyl-LSD (ALD-52), a derivative of LSD containing an acetyl group on the indole nitrogen, also produces psychedelic effects in humans and has about the same potency as LSD. Recently, several other 1-acyl-substitued LSD derivatives, including 1-propanoyl-LSD (1P-LSD) and 1-butanoyl-LSD (1B-LSD), have appeared as designer drugs. Although these compounds are assumed to act as prodrugs for LSD, studies have not specifically tested this prediction. The present investigation was conducted to address the gap of information about the pharmacological effects and mechanism-of-action of 1-acyl-substituted LSD derivatives. Competitive binding studies and calcium mobilization assays were performed to assess the interaction of ALD-52, 1P-LSD, and 1B-LSD with serotonin 5-HT 2 receptor subtypes. A receptorome screening was performed with 1B-LSD to assess its binding to other potential targets. Head twitch response (HTR) studies were performed in C57BL/6J mice to assess in vivo activation of 5-HT 2A (the receptor thought to be primarily responsible for hallucinogenesis). Finally, liquid chromatography/ion-trap mass spectrometry (LC/MS) was used to quantify plasma levels of LSD in Sprague-Dawley rats treated with ALD-52 and 1P-LSD. 1-Acyl-substitution reduced the affinity of LSD for most monoamine receptors, including 5-HT 2A sites, by one to two orders of magnitude. Although LSD acts as an agonist at 5-HT 2 subtypes, ALD-52, 1P-LSD and 1B-LSD have weak efficacy or act as antagonists in Ca 2+ -mobilization assays. Despite the detrimental effect of 1-acyl substitution on 5-HT 2A affinity and efficacy, 1-acyl-substitued LSD derivatives induce head twitches in mice with relatively high potency. High levels of LSD were detected in the plasma of rats after subcutaneous administration of ALD-52 and 1P-LSD, demonstrating these compounds are rapidly and efficiently deacylated in vivo. These findings are consistent with the prediction that ALD-52, 1P-LSD and 1B-LSD serve as prodrugs for LSD. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'., Competing Interests: Declaration of competing interest None., (Copyright © 2019. Published by Elsevier Ltd.)

The remarkable effects exhibited by classical psychedelics in recent clinical trials have spawned considerable interest in 5-HT 2A receptor (5-HT 2A R) activation as a treatment strategy for several psychiatric/cognitive disorders. In this study we have continued our development of 25CN-NBOH, one of the most 5-HT 2A R-selective agonists reported to date, as a pharmacological tool for exploration of 5-HT 2A R expression and functions. The importance of the 2' and 3' positions in 25CN-NBOH as structural hotspots for its 5-HT 2A R activity was investigated by synthesis and pharmacological characterization of six novel analogs at 5-HT 2A R and 5-HT 2C R in binding and functional assays. While the 5-HT 2A R activity of 25CN-NBOH was retained in 3'-methyl, 2',3'-chroman, 2',3'-dihydrofuran and 2',3'-furan analogs, the 3'-methoxy and 3'-ethyl analogs displayed substantially lower binding affinities and agonist potencies than 25CN-NBOH. Interestingly, the 2',3'-substitution pattern was also a key determinant of agonist efficacy, as all six analogs exhibited low-efficacy partial agonism or de facto antagonism at the 5-HT 2A R in the functional assays. Systemic administration of 25CN-NBOH and its close structural analog 25CN-NBMD induced robust head-twitch response in mice, a well-established behavioural effect of 5-HT 2A R activation in vivo, and 25CN-NBOH mediated robust reductions in the activity of mice in an anxiety-related marble burying assay, which supports the proposed beneficial effects of 5-HT 2A R activation on disorders characterized by cognitive rigidity. Finally, tritiated 25CN-NBOH exhibited high 5-HT 2A R binding affinity (K D ~1 nM) and selectivity against 5-HT 2B R and 5-HT 2C R in equilibrium and kinetic binding studies of the recombinant receptors, and in concordance [ 3 H]25CN-NBOH displayed substantial specific, ketanserin-sensitive binding to cortex and small levels of binding to choroid plexus in rat brain slices in autoradiography studies. In conclusion, this work delineates the subtle molecular determinants of the 5-HT 2A R activity in 25CN-NBOH, substantiates the potential in this compound and its analogs as tools for in vivo studies of the 5-HT 2A R, and introduces a novel selective agonist radioligand as another potentially valuable tool for future explorations of this receptor., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The 2,5-dimethoxyphenethylamine (2,5-PEA) scaffold is recognized as a motif conferring potent agonist activity at the serotonin 2A receptor (5-HT 2A R). The 2,5-dimethoxy motif is present in several classical phenethylamine psychedelics such as 2,4,5- trimethoxyamphetamine (TMA-2), 2,5-dimethoxy-4-methylamphetamine (DOM), 2,5-dimethoxy-4-iodoamphetamine (DOI), 2,5- dimethoxy-4-bromoamphetamine (DOB), 2,5-dimethoxy-4-bromophenethylamine (2C-B), and 2,5-dimethoxy-4-iodophenethylamine (2C-I), and it has previously been suggested that this structural motif is essential for 5-HT 2A R activation. In the present study, we present data that challenges this assumption. The 2- and 5-desmethoxy derivatives of 2C-B and DOB were synthesized, and their pharmacological profiles were evaluated in vitro at 5-HT 2A R and 5-HT 2C R in binding and functional assays and in vivo by assessing their induction of the head-twitch response in mice. Elimination of either the 2- or 5-methoxy group leads to a modest drop in binding affinity and functional potency at 5-HT 2A R and 5-HT 2C R, which was more pronounced upon removal of the 2-methoxy group. However, this trend was not mirrored in vivo , as removal of either methoxy group resulted in significant reduction in the ability of the compounds to induce the head-twitch response in mice. Thus, the 2,5-dimethoxyphenethylamine motif appears to be important for in vivo potency of phenethylamine 5-HT 2A R agonists, but this does not correlate to the relative affinity and potency of the ligands at the recombinant 5-HT 2A R.

Serotonergic hallucinogens such as lysergic acid diethylamide (LSD) induce head twitches in rodents via 5-HT 2A receptor activation. The goal of the present investigation was to determine whether a correlation exists between the potency of hallucinogens in the mouse head-twitch response (HTR) paradigm and their reported potencies in other species, specifically rats and humans. Dose-response experiments were conducted with phenylalkylamine and tryptamine hallucinogens in C57BL/6J mice, enlarging the available pool of HTR potency data to 41 total compounds. For agents where human data are available (n = 36), a strong positive correlation (r = 0.9448) was found between HTR potencies in mice and reported hallucinogenic potencies in humans. HTR potencies were also found to be correlated with published drug discrimination ED 50 values for substitution in rats trained with either LSD (r = 0.9484, n = 16) or 2,5-dimethoxy-4-methylamphetamine (r = 0.9564, n = 21). All three of these behavioral effects (HTR in mice, hallucinogen discriminative stimulus effects in rats, and psychedelic effects in humans) have been linked to 5-HT 2A receptor activation. We present evidence that hallucinogens induce these three effects with remarkably consistent potencies. In addition to having high construct validity, the HTR assay also appears to show significant predictive validity, confirming its translational relevance for predicting subjective potency of hallucinogens in humans. These findings support the use of the HTR paradigm as a preclinical model of hallucinogen psychopharmacology and in structure-activity relationship studies of hallucinogens. Future investigations with a larger number of test agents will evaluate whether the HTR assay can be used to predict the hallucinogenic potency of 5-HT 2A agonists in humans. "This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'., Competing Interests: Declaration of competing interest None., (Published by Elsevier Ltd.)

1,2-Diarylethylamines represent a class of molecules that have shown potential in the treatment of pain, epilepsy, neurodegenerative disease and depression. Examples include lefetamine, remacemide, and lanicemine. Recently, several 1,2-diarylethylamines including the dissociatives diphenidine, methoxphenidine and ephenidine as well as the opioid MT-45, have appeared as 'research chemicals' or 'legal highs'. Due to their recent emergence little is known about their pharmacology. One of these, 1-[1-(2-fluorophenyl)-2-phenylethyl]pyrrolidine (fluorolintane, 2-F-DPPy), is available for purchase with purported dissociative effects intended to resemble phencyclidine (PCP) and ketamine. To better understand this emerging class, pharmacological investigations were undertaken for the first time on fluorolintane and its five aryl-fluorine-substituted isomers. In vitro binding studies revealed high affinity for N-methyl-D-aspartate (NMDA) receptors with fluorolintane (K i  = 87.92 nM) with lesser affinities for related compounds. Additional affinities were seen for all compounds at several sites including norepinephrine (NET), serotonin (SERT) and dopamine (DAT) transporters, and sigma receptors. Notably high affinities at DAT were observed, which were in most cases greater than NMDA receptor affinities. Additional functional and behavioral experiments show fluorolintane inhibited NMDA receptor-induced field excitatory postsynaptic potentials in rat hippocampal slices and inhibited long-term potentiation induced by theta-burst stimulation in rat hippocampal slices with potencies consistent with its NMDA receptor antagonism. Finally fluorolintane inhibited prepulse inhibition in rats, a measure of sensorimotor gating, with a median effective dose (ED 50 ) of 13.3 mg/kg. These findings are consistent with anecdotal reports of dissociative effects of fluorolintane in humans., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: In recent years, there has been increasing scientific interest in the effects and pharmacology of serotonergic hallucinogens. While a large amount of experimental work has been conducted to characterize the behavioral response to hallucinogens in rodents, there has been little systematic investigation of mescaline and its analogs. The hallucinogenic potency of mescaline is increased by α-methylation and by homologation of the 4-methoxy group but it not clear whether these structural modifications have similar effects on the activity of mescaline in rodent models., Methods: In the present study, the head twitch response (HTR), a 5-HT 2A receptor-mediated behavior induced by serotonergic hallucinogens, was used to assess the effects of mescaline and several analogs in C57BL/6J mice. HTR experiments were conducted with mescaline, escaline (4-ethoxy-3,5-dimethoxyphenylethylamine) and proscaline (3,5-dimethoxy-4-propoxyphenylethylamine), their α-methyl homologs TMA (3,4,5-trimethoxyamphetamine), 3C-E (4-ethoxy-3,5-dimethoxyamphetamine) and 3C-P (3,5-dimethoxy-4-propoxyamphetamine), and the 2,4,5-substituted regioisomers TMA-2 (2,4,5-trimethoxyamphetamine), MEM (4-ethoxy-2,5-dimethoxyamphetamine) and MPM (2,5-dimethoxy-4-propoxyamphetamine)., Results: TMA induced the HTR and was twice as potent as mescaline. For both mescaline and TMA, replacing the 4-methoxy substituent with an ethoxy or propoxy group increased potency in the HTR assay. By contrast, although TMA-2 also induced the HTR with twice the potency of mescaline, potency was not altered by homologation of the 4-alkoxy group in TMA-2., Conclusions: The potency relationships for these compounds in mice closely parallel the human hallucinogenic data. These findings are consistent with evidence that 2,4,5- and 3,4,5-substituted phenylalkylamine hallucinogens exhibit distinct structure-activity relationships. These results provide additional evidence that the HTR assay can be used to investigate the structure-activity relationships of serotonergic hallucinogens.

Background: There is evidence that mGlu2/3 receptors regulate 5-HT 2A signaling, interactions that have been theorized to play a role in the antipsychotic-like effects of mGlu2/3 agonists as well as the hallucinogenic effects of 5-HT 2A agonists. One approach to unraveling this interaction is through the chronic administration of agonists at the two receptors, which should influence the functional properties of the targeted receptor due to receptor downregulation or desensitization and thereby alter crosstalk between the two receptors. In this study, we investigated whether chronic treatment with the mGlu2/3 agonist LY379268 would alter the behavioral response to a phenethylamine hallucinogen, 25CN-NBOH, which acts as a selective 5-HT 2A agonist., Methods: We first conducted a dose response of 25CN-NBOH (0.1, 0.3, 1, 3, or 10 mg/kg) to confirm the effects on head-twitch response (HTR) and then blockade studies with either the M100907 (0.1 mg/kg) or SB242084 (0.1, 0.3, or 1 mg/kg) to determine the contribution of 5-HT2A and 5-HT2C to 25CN-NBOH-induced HTR, respectively. To determine whether an mGlu2/3 agonist could block 25CN-NBOH-induced HTR, mice were pretreated with vehicle or LY379268 (0.1, 1, or 10 mg/kg) prior to 25CN-NBOH, and HTR was assessed. The effects of chronic LY379268 on 5-HT2A agonist-induced HTR were evaluated by treating mice with either vehicle or LY379268 (10 mg/kg) for 21 days and measuring 25CN-NBOH-induced HTR 48 h after the final LY379268 treatment. The following day (72 h after the final LY379268 treatment), the ability of acute LY379268 to block PCP-induced locomotor activity was assessed., Results: 25CN-NBOH dose-dependently increased the HTR, a 5-HT 2A -mediated behavior, in mice. The selective 5-HT 2A antagonist M100907 completely blocked the HTR induced by 25CN-NBOH, whereas the selective 5-HT 2C antagonist SB242084 had no effect on the HTR. Administration of LY379268 (10 mg/kg SC) attenuated the HTR induced by 1 mg/kg 25CN-NBOH by ~ 50%. Chronic treatment (21 days) with LY379268 also attenuated the HTR response to 25CN-NBOH when tested 48 h after the last dose of LY379268. In locomotor tests, acute LY379268 significantly attenuated PCP-induced locomotor activity in the chronic vehicle treatment group; by contrast, there was only a trend for an overall interaction in the chronic LY379268 group, with LY379268 blocking the locomotor-stimulating effects of PCP only during the last 20 min., Conclusions: These data are consistent with a functional interaction between mGlu2/3 and 5-HT 2A receptors, although the specific mechanism for the interaction is not known. These data support the hypothesis that mGlu2/3 receptors play a prominent role in modulating the behavioral response to 5-HT 2A receptor activation.

The author of this article wanted to change the Acknowledgments section to: These studies were supported by an award from NIDA (R01 DA041336), as well as by the Veteran's Administration VISN 22 Mental Illness Research, Education, and Clinical Center. Receptor binding and functional data were generously.

Rationale: The lysergamide lysergic acid diethylamide (LSD) is a prototypical classical hallucinogen with remarkably high potency. LSD remains a popular recreational drug but is also becoming an important research tool for medical and neuroscience studies. Recently, several lysergamides that are close structural analogs of LSD have been sold as recreational drugs, which suggests that further studies are needed to explore the pharmacological properties of these compounds., Objective: In this present investigation, another LSD congener, N-ethyl-N-cyclopropyl lysergamide (ECPLA), which to date has not been marketed as a recreational substance, was evaluated for its pharmacological features relative to those previously reported for LSD. The experiments focused on interactions with the 5-HT 2A receptor, which is responsible for mediating the psychedelic effects of LSD and other hallucinogens., Methods: Competitive binding assays were performed to measure the affinity of ECPLA for 27 monoamine receptors. The ability of ECPLA to activate human 5-HT 2 receptor subtypes was assessed using calcium mobilization assays. Head twitch response (HTR) studies were conducted in C57BL/6J mice to determine whether ECPLA activates 5-HT 2A receptors in vivo. Two other N-alkyl substituted lysergamides, N-methyl-N-isopropyl lysergamide (MIPLA) and N-methyl-N-propyl lysergamide (LAMPA), were also tested in the HTR paradigm for comparative purposes., Results: ECPLA has high affinity for most serotonin receptors, α 2 -adrenoceptors, and D 2 -like dopamine receptors. Additionally, ECPLA was found to be a potent, highly efficacious 5-HT 2A agonist for Gq-mediated calcium flux. Treatment with ECPLA induced head twitches in mice with a median effective dose (ED 50 ) of 317.2 nmol/kg (IP), which is ~ 40% of the potency observed previously for LSD. LAMPA (ED 50  = 358.3 nmol/kg) was virtually equipotent with ECPLA in the HTR paradigm whereas MIPLA (ED 50  = 421.7 nmol/kg) was slightly less potent than ECPLA., Conclusions: These findings demonstrate that the pharmacological properties of ECPLA, MIPLA, and LAMPA are reminiscent of LSD and other lysergamide hallucinogens.

In recent years, rigid analogs of phenylalkylamine hallucinogens have appeared as recreational drugs. Examples include 2-(8-bromo-2,3,6,7-tetrahydrobenzo[1,2-b:4,5-b']difuran-4-yl)ethan-1-amine (2C-B-FLY) and 1-(8-bromobenzo[1,2-b;4,5-b']difuran-4-yl)-2-aminopropane (Bromo-DragonFLY, DOB-DFLY). Although some rigid compounds such as DOB-DFLY reportedly have higher potency than their non-rigid counterparts, it is not clear whether the same is true for 2C-B-FLY and other tetrahydrobenzodifurans. In the present study, the head twitch response (HTR), a 5-HT 2A receptor-mediated behavior induced by serotonergic hallucinogens, was used to assess the effects of 2,5-dimethoxy-4-bromoamphetamine (DOB) and its α-desmethyl homologue 2,5-dimethoxy-4-bromophenethylamine (2C-B), as well as their benzodifuranyl and tetrahydrobenzodifuranyl analogs, in C57BL/6J mice. DOB (ED 50  = 0.75 μmol/kg) and 2C-B (ED 50  = 2.43 μmol/kg) induced the HTR. The benzodifurans DOB-DFLY (ED 50  = 0.20 μmol/kg) and 2C-B-DFLY (ED 50  = 1.07 μmol/kg) had significantly higher potency than DOB and 2C-B, respectively. The tetrahydrobenzodifurans DOB-FLY (ED 50  = 0.67 μmol/kg) and 2C-B-FLY (ED 50  = 1.79 μmol/kg), by contrast, were approximately equipotent with their non-rigid counterparts. Three novel tetrahydrobenzodifurans (2C-I-FLY, 2C-E-FLY and 2C-EF-FLY) were also active in the HTR assay but had relatively low potency. In summary, the in vivo potency of 2,5-dimethoxyphenylalkylamines is enhanced when the 2- and 5-methoxy groups are incorporated into aromatic furan rings, whereas potency is not altered if the methoxy groups are incorporated into dihydrofuran rings. The potency relationships for these compounds in mice closely parallel the human hallucinogenic data. The high potency of DOB-DFLY is probably linked to the presence of two structural features (a benzodifuran nucleus and an α-methyl group) known to enhance the potency of phenylalkylamine hallucinogens., (Published by Elsevier Ltd.)

Chronic inflammation is a major cause of morbidity and mortality in end-stage renal disease. The associated anemia in these patients due to renal cortical atrophy and erythropoietin deficiency is treated with recombinant erythropoietin. Recent reports suggest a growing incidence of symptomatic venous thrombosis in cancer patients treated with recombinant erythropoietin. Several investigators have reported on different mechanisms of thrombosis in these patients. We hypothesize that thrombosis in patients with end-stage renal disease due to increased expression of C-reactive protein (CRP) as a result of chronic inflammation promotes the release of thrombin activatable fibrinolytic inhibitor causing fibrinolytic deficit and eventually thrombosis. Furthermore, because endothelial nitric oxide is responsible for the maintenance of the normal vascular function, the decreased levels of nitric oxide in chronic inflammation cause endothelial damage and result in thrombosis. To test this hypothesis, blood samples were collected from 106 patients (49 male and 57 female, aged 59.8+/-15.7 years) with end-stage renal disease undergoing hemodialysis and treated with recombinant erythropoietin at a mean dose of 201.8 U/kg/week. Blood samples were drawn in 5-mL tubes containing 3.2% sodium citrate just before the hemodialysis procedure. These blood samples were immediately centrifuged to obtain platelet-poor plasma, which was aliquoted and frozen at -70 degrees C until further analysis. Erytropoietin antibodies were measured using an anti-EPO enzyme-linked immunosorbent assay (ELISA) method developed in our laboratory. Nitric oxide was measured using a NO analyzer (Sievers 280I, Ionics, Boulder, CO). Plasma CRP levels were measured with a highly sensitive ELISA method IMUNOCLONE CRP ELISA (American Diagnostica, Greenwich, CT). TAFI antigen levels in plasma were analyzed with an IMUCLONE TAFI ELISA kit (American Diagnostica, Greenwich, CT). TAFI functional activity was assayed with an ACTICHROME TAFI activity kit. The measured levels of nitric oxide, CRP, TAFI antigen, and TAFI functional were 37.36+/-36.8 (normal value, 37.49+/-18.96; range, 19.3-102 microM), 12.27+/-10.6 (normal value, < 1 microg/mL), 146.9+/-28.4% NHP (normal, 100% NHP), and 102.55+/-37% NHP (normal range, 22.3-165.7; mean, 89.5% NHP), respectively. The erythropoietin antibody was detected in 9.4% of the patient group. While 20% of the erythropoietin antibody-positive and 27.1% of the erythropoietin antibody-negative patients experienced chest pain, thrombotic events developed in 9.4% of the erythropoietin antibody-negative patients. These data provide the rationale for a novel mechanism of thrombosis through increased activity of CRP, nitric oxide, and TAFI, leading to fibrinolytic deficit and thrombosis in patients treated with erythropoietin.