Enamel Surface Roughness after Debonding: A Comparative Study using Three Different Burs.

AIM: To compare effects of three different burs, i.e., tungsten carbide bur, composite bur, and fiber glass bur on the surface roughness of enamel after debonding evaluated by means of profilometry. MATERIALS AND METHODS: The present study was conducted in the Department of Orthodontics and Dentofacial Orthopedics, Guru Nanak Dev Dental College and Research Institute, Sunam, Punjab, India, from August 2011 to December 2012 on 36 extracted premolars. After mounting the samples in acrylic blocks with their buccal surfaces exposed, initial measurement of the surface roughness was made using profilometry. Teeth were then etched and brackets were bonded with light cure adhesive. After 3 days, the brackets were debonded using three different rotating burs at low speed, i.e., tungsten carbide bur, fiber glass bur, and composite bur. Enamel surface roughness values were obtained and assessed using paired t-test, one-way analysis of variance (ANOVA) test, and post hoc multiple tests. RESULTS: Surface roughness of enamel increased significantly for tungsten carbide bur when compared with fiber glass bur and composite bur. But there was no significant difference in the surface roughness value when fiber glass bur was compared with the composite bur. CONCLUSION: Composite and fiber glass burs used for resin removal after orthodontic debonding produced a smoother enamel surface as compared with the tungsten carbide bur. CLINICAL SIGNIFICANCE: After an orthodontic treatment, restoring the enamel surface to its pretreatment condition without inducing any iatrogenic damage after debonding is a clinical challenge. Residual resin removal through proper means ensures a smooth surface, and, hence, a plaque-free environment. Finishing requires as much planning and execution as planned for the fixed therapy itself.

Nanocarriers and Diabetes: New Vistas and the Way Ahead.

World Health Organization has reported an estimated 1.5 million deaths directly due to diabetes in 2019. Center for Disease Control and Prevention, in its National Diabetes Statistics Report, 2020, says that 1 in 10 United States residents has diabetes. This rapid progression of diabetes is noteworthy despite significant advances in the field of antidiabetic medicine. The critical challenges in treatment are dyslipidemia, hyperinsulinemia, and hyperglycemia. The latest research has also linked diabetes to carcinogenesis. The diabetic condition accelerates cell growth, proliferation, migration, inflammation, angiogenesis, metastasis, and inhibition of apoptosis in cancer cells. In addition, diabetic complications of nephropathy, retinopathy, neuropathy, cardiomyopathy, peripheral arterial disease, coronary artery disease, and stroke increase morbidity. Amidst all these challenges, a ray of hope is the advent of nanocarriers. The nano size helps in the targeted and controlled delivery of drugs. In addition, nanocarrier formulation helps in the delivery of acid-labile and enzyme- labile molecules and plant-based macromolecules via the oral route. Its use in the form of dendrimers, ethosomes, niosomes, transfersomes, and polymeric nanoparticles is established. In addition, different polymers used to formulate nanocarriers are also established for targeting diabetes. Thus, this review aims to compile approaches involving the use of nanocarriers for the betterment of pharmacotherapy of diabetes and to provide a way ahead for researchers in the field.

Increased serotonergic neurotransmission is not responsible for the anticompulsive effect of berberine in a murine model of obsessive-compulsive disorder.

Berberine, an isoquinoline alkaloid, is being extensively explored in several clinical trials for the treatment of metabolic disorder and cancer. It is also reported to be a potent inhibitor of prolyl oligopeptidase, which makes it a potential candidate for the treatment of neuropsychiatric disorders. We have previously shown the potential of berberine in the control of seizures in various murine models of epilepsy, diabetes-induced memory dysfunction, and ethanol-induced hyperexcitability. We have now examined the effects of acute and subchronic (7 days) administration of berberine on a murine model of obsessive-compulsive disorder - the marble-burying behavior of male mice, because berberine administration is reported to increase brain monoamine levels - a desirable endpoint in the treatment of obsessive-compulsive disorder. The studies showed that an acute administration of berberine [1-25 mg/kg, intraperitoneally (i.p.)] dose-dependently inhibited marble burying in male mice without altering locomotor activity. This effect was retained after its subchronic administration. Furthermore, coadministration of a subeffective dose of berberine (1 mg/kg) and fluoxetine (5 mg/kg, i.p.) significantly reduced marble burying in mice. Pretreatment with p-chlorophenylamine (300 mg/kg, i.p. ×3 days), a tryptophan hydroxylase inhibitor and serotonin-depleting agent, completely blocked the effect of fluoxetine on marble burying, whereas it failed to alter the effect of berberine. In conclusion, the findings of the present investigation indicate that the anticompulsive and/or anxiolytic effect of berberine observed in the present investigation may be attributed to its effect on other neurotransmitter systems, such as the nitrergic or the dopaminergic system rather than to increased serotonin turnover in the brain.

Influence of sigma-1 receptor modulators on ethanol-induced conditioned place preference in the extinction-reinstatement model.

Sigma-1 receptor agonists are reported to augment and antagonists block the rewarding effects of drugs of abuse. However, their effect on reinstatement of ethanol-induced conditioned place preference (CPP) has not yet been explored. Therefore, we investigated the ability of 2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate (PRE-084), a sigma-1 receptor agonist, and N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino) ethylamine dihydrobromide (BD-1047), a sigma-1 receptor antagonist, on the acquisition, expression, and reinstatement of ethanol-induced CPP using adult male Swiss mice. BD-1047 (0.1-10 µg/mouse, intracerebroventricularly) dose-dependently blocked the development, expression, and reinstatement of ethanol-induced CPP, and PRE-084 (0.01-10 µg/mouse, intracerebroventricularly) dose-dependently reinstated the extinguished response. These effects of PRE-084 and BD-1047 alone or in combination with ethanol did not influence the motor activity. Therefore, it is concluded that sigma-1 receptor ligands can modulate the acquisition, expression, and reinstatement of conditioned reinforcing effects of ethanol with no reinforcing or aversive influence of their own. The results add to the growing literature on sigma-1 receptor modulation in the pharmacotherapy of ethanol addiction.

Differential effect of oxidative stress on intestinal apparent permeability of drugs transported by paracellular and transcellular route.

Increased intestinal permeability of macromolecules is a common feature of oxidative stress-induced gastrointestinal diseases; how it affects the absorption of drugs is not investigated. Hence, it was proposed to study the influence of hydrogen peroxide-induced oxidative stress on permeability of atenolol and metoprolol using a modified everted rat intestine technique. Atenolol was chosen as a marker of paracellular drug transport and metoprolol was selected to represent transcellular drug transport. Wistar rats were used as a source of intestine, which was everted using a glass rod, mounted on permeability apparatus, having test drug (100 µg/ml in Krebs) in donor compartment. Samples were taken from receiver compartment every 5 min for 60 min, and analyzed by HPLC. For induction of oxidative stress isolated ileum was incubated in H2O2 (200 µM) containing Krebs for 15 min and then again permeability was estimated. Extent of oxidative stress was determined by estimating lipid peroxidation using thiobarbituric acid assay, which was found to be increased by 42 % in hydrogen peroxide treated rat intestine as compared to control group. The mean apparent permeability of atenolol and metoprolol was found to be 0.054 ± 0.024 × 10⁻4 and 0.84 ± 0.14 × 10⁻4 cm/s, respectively, in control group rat intestinal segments. After exposure to hydrogen peroxide, there was a significant increase in the mean permeability of atenolol (0.11 ± 0.01 × 10⁻4 cm/s), however, metoprolol permeability was unaltered (0.94 ± 0.047 × 10⁻4 cm/s). The marked increase in the apparent permeability of atenolol may be attributed to rupture of intestinal barrier. In conclusion, the present study reports the differential effect of oxidative stress-induced damage on drug transport across rat intestine.

Features and Facts of a Gastroretentive Drug Delivery System-A Review.

English oral delivery of drug was the commonly used modality because of patient compliance and ease of administration. After oral administration of any drug, its bioavailability is affected by its residence time in stomach. Recently, gastroretentive drug delivery systems (GRDDS) have gained wide acceptance for drugs with a narrow absorption window, decreased stability at high alkaline pH, and increased solubility at low pH. This approach develops a drug delivery system, which gets retained within gastric fluid, thereby releasing its active principles in the stomach. Some methods used to achieve gastric retention of drugs include the use of effervescence agents, mucoadhesive polymers, magnetic material, bouncy enhancing excipient, and techniques that form plug-like devices that resist gastric emptying. This review provides a concise account of various attributes of recently developed approaches for GRDDS.

Berberine protects C57BL/6J mice against ethanol withdrawal-induced hyperexcitability.

Berberine ([C20H18NO4](+) ), one of the major constituents of the Chinese herb Rhizoma coptidis, is an isoquinoline alkaloid. Plethora of recent reports has indicated its ability to modulate several neurotransmitter systems, especially those implicated in ethanol dependence. Thus, the influence of berberine treatment on the development and expression of ethanol dependence was tested by using the ethanol withdrawal-induced hyperexcitability paradigm. Mice were provided with a nutritionally balanced control liquid diet as the sole nutrient source on day 0; from day 1-4 (ethanol, 3% v/v), from day 5-7 (ethanol, 6% v/v) and from day 8-10 (ethanol, 10% v/v) was incorporated into the liquid diet. On day 11, the ethanol liquid diet was replaced with nutritionally balanced control liquid diet, and ethanol withdrawal-induced hyperexcitability signs were recorded. The results revealed that acute administration of berberine (10 and 20 mg/kg, i.p.) dose-dependently attenuated ethanol withdrawal-induced hyperexcitability signs, and these results were comparable to diazepam (1.25 and 2.5 mg/kg, i.p.). Further, chronic administration of berberine (10 and 20 mg/kg, i.p.) to the ethanol diet fed mice markedly attenuated the ethanol withdrawal-induced hyperexcitability signs. In conclusion, the results and evidence suggest that berberine exhibited an inhibitory influence against ethanol withdrawal-induced hyperexcitability signs, which could be mediated through its neuromodulatory action.

Ameliorative effect of quercetin on memory dysfunction in streptozotocin-induced diabetic rats.

Diabetes-related cognitive dysfunction is a consequence of changes within the central nervous system that are secondary to chronic hyperglycemia, oxidative stress, and cholinergic dysfunction, and probably therefore anti-diabetics, anti-oxidants, and acetylcholine esterase (AChE) inhibitors were found to have beneficial effects in animal models. Quercetin, a bioflavonoid widely distributed in the plants is reported to be a potent anti-diabetic, anti-oxidant, AChE inhibitor, and memory enhancer. Therefore, we screened its influence against diabetes-induced cognitive dysfunction in streptozotocin-induced diabetic rats using Morris water and elevated plus maze (EPM) paradigms. Thirty days after diabetes induction rats exhibited marked and persistent hyperglycemia, weight loss, higher escape latency during training trials and reduced time spent in target quadrant in probe trial in Morris water maze test, and increased escape latency in EPM task. Treatment with quercetin (5-20 mg/kg, p.o., twice daily, 30 days) in streptozotocin-induced diabetic rats prevented the changes in blood glucose, body weight, and performance in Morris water and elevated plus maze tasks. In another set of experiment, quercetin (40 mg/kg, p.o., twice daily) treatment during training trials (31-35 days) markedly decreased escape latency and increased time spent in target quadrant during Morris water maze task. This treatment also decreased blood glucose levels, but had no influence on body weights. These effects were comparable to vitamin C (100 mg/kg, twice daily, 30 days) and donepezil (3 mg/kg day 31-day 35, during training trials), and devoid of any motor deficit and anxiety-like effect when tested in open field test. In conclusion, quercetin may provide a new potential option for prevention of the cognitive dysfunction in diabetes.

Inhibitory influence of mecamylamine on ethanol withdrawal-induced symptoms in C57BL/6J mice.

Several reports show the involvement of neuronal nicotinic acetylcholine receptors (nAChRs) in the behavioral effects of ethanol, including ethanol drinking and relapse. Therefore, this study evaluated the effects of mecamylamine, a nAChR antagonist, on ethanol withdrawal signs. Ethanol dependence was induced in C57BL/6J mice by ethanol liquid diet administration. Animals were provided with nutritionally balanced control liquid diet (600 kcal/l) as their sole nutrient source on day 0; from days 1 to 4, 3% v/v of ethanol, followed by 6% v/v of ethanol (from days 5 to 7), and 10% v/v of ethanol (from days 8 to 10) were incorporated into the liquid diet. On day 11, ethanol liquid diet was replaced with nutritionally balanced control liquid diet, and ethanol withdrawal-induced physical signs were recorded. Results showed that acute administration of mecamylamine (1-4 mg/kg, intraperitoneally) dose-dependently attenuated ethanol withdrawal-induced signs, and these effects were comparable with those of diazepam (1-2 mg/kg, intraperitoneally). In addition, chronic administration of mecamylamine into ethanol diet-fed mice markedly attenuated the ethanol withdrawal sign scores, thus supporting the contention that nAChR is involved in ethanol dependence. In conclusion, our results suggest that mecamylamine exhibited inhibitory effects on ethanol withdrawal signs which could be mediated through nAChR.

Anticonvulsant activity of berberine, an isoquinoline alkaloid in mice.

Berberine, an isoquinoline alkaloid is reported to modulate several neurotransmitter systems like N-methyl-D-aspartate, nitric oxide and serotonin, which modulate convulsions. In addition, it is suggested that Berberis vulgaris may be useful in treatment of convulsion and epilepsy. Therefore, the present study investigated the effects of berberine in pentylenetetrazole, maximal electroshock (MES) and kainic acid (KA)-induced convulsions. The latency for development of convulsions and mortality rate was recorded in these models using mice. The results revealed that in MES-induced seizures model, berberine (10 and 20 mg/kg, i.p.) decreased duration of tonic hind limb extension and percent mortality. Moreover, these doses of berberine also protected mice against KA-induced clonic convulsions and decreased mortality. Berberine also protected mice against NMDA-induced turning behavior. Further, the anticonvulsant doses of berberine did not show any signs of motor in-coordination when tested in rotarod test. In conclusion, berberine exhibits anticonvulsant activity by modulating neurotransmitter systems and may find clinical application.

Marble-burying behavior test as a murine model of compulsive-like behavior.

Object burying by rodents is a popular screening tool for anxiolytic agents. However, modulation of marble-burying by serotonin reuptake inhibitors prompted its link to obsessive-compulsive disorder/compulsive-like behavior. The Marble-burying behavior test is an acute test; however, some investigators incorporate the sub-acute treatment regimen as an essential component for screening anti-compulsive agents. The test exhibits between-laboratory methodological differences and demonstrates positive treatment responses to an array of pharmacotherapies, creating doubts about its predictive validity and construct validity. Numerous reviews are available on marble-burying behavior test, which incorporates the test as a part of anti-compulsive behavior-like screens, but none has made it a sole subject-matter for discussion. This review attempts to provide a comprehensive account of the marble-burying test as a model of compulsive-like disorders. It envisages the model's scientific origins, the preclinical research done and its correlation with the clinical research outcomes, and a detailed discussion about its validity. In conclusion, there appears a need to address the issue of construct and predictive validity of the model authoritatively; or the paradigm may remain squandered in the field of obsessive-compulsive disorder research.

Increased marble-burying behavior in ethanol-withdrawal state: modulation by gonadotropin-releasing hormone agonist.

A characteristic behavior in alcohol abstinence state indicates the possibility of obsessive-compulsive behavior in alcoholics. Ethanol is known to reduce hypothalamic synthesis, release, and mRNA expression of gonadotropin-releasing hormone (GnRH) that modulates serotonergic, dopaminergic, and glutamatergic systems, which experience adaptive changes on chronic exposure to ethanol. Such changes are also evident in obsessive-compulsive disorder. Therefore, it was proposed to investigate the effect of ethanol-withdrawal on marble-burying behavior in mice, particularly because it simulates some aspects of obsessive-compulsive behavior; further, the influence of GnRH agonist was studied on the same. Ethanol-withdrawal state was induced after its chronic administration, and marble-burying behavior was observed at 0, 6, 24, 48, and 96 h interval. Further, the influence of leuprolide--a GnRH agonist (50-600 microg/kg, s.c.) or fluoxetine (5-30 mg/kg, i.p.) was investigated on ethanol-withdrawal-induced changes in marble-burying behavior. The results indicated that ethanol-withdrawal led to a gradual increase in marble-burying behavior upto 48 h with peak at 24 h interval. Administration of leuprolide (100-600 microg/kg, s.c.), 30 min prior to 24 h interval, dose dependently reduced ethanol-withdrawal-induced increase in marble-burying behavior, and this effect was comparable to that of fluoxetine (15 and 30 mg/kg, i.p.). Further, twice daily administration of leuprolide (50 microg/kg, s.c), concomitant with ethanol, prevented the gradual increase in marble-burying behavior after ethanol-withdrawal and this effect was comparable to fluoxetine (5 mg/kg, i.p.). In conclusion, ethanol-withdrawal on chronic administration increases marble-burying behavior in mice; its development and expression is attenuated by leuprolide.

Pain Perception and Personality Trait toward Orthodontic Treatment.

AIM: The study was done to evaluate the pain perception, attitude, and personality trait of the patient toward orthodontic treatment. MATERIALS AND METHODS: In this cross-sectional questionnaire survey, 100 patients were divided into Group 1, 150 (75 males and 75 females) as untreated group and Group 2, 150 as treated group (75 males and 75 females). Evaluation of the patients was done based on pain perception, attitude, and personality trait. Set of questionnaire was used to assess attitude and pain perception on visual analog scale. The data were tabulated, and statistical evaluation was done using statistical software IBM SPSS Statistics for Windows, (Version 21.0. Armonk, NY: IBM Corp.) using t-test and Tukey's test. RESULTS: The mean pain perception for Group 1 was 4.8 ± 1.30 and 4.17 ± 1.58 in Group 2; the difference was not statistically significant (P = 0.26). The mean value for attitude in Group 1 was 3.57 ± 1.21, and in Group 2, it was 3.39 ± 1.60 (P = 0.09). There was statistically significant difference in pain perception between low (L) level to high level (H) neuroticism (P = 0.009). There was significant difference (P = 0.021) in pain for conscientiousness from very low to very high levels which is directly proportional. CONCLUSION: The present study indicated that attitude, personality traits, and pain perception have a definite role in patient cooperation and success of orthodontic treatment.

Effects of agomelatine in a murine model of obsessive-compulsive disorder: interaction with meta-chlorophenylpiperazine, bicuculline, and diazepam.

The anticompulsive potential of agomelatine, a potent MT1/2 receptor agonist, and its combined effect with m-chlorophenylpiperazine hydrochloride (mCPP), bicuculline, and diazepam, were investigated in male C57BLJ/6 mice using marble-burying behavior (MBB) test. Acute administration of agomelatine (30-40 mg/kg, intraperitoneal (i.p.)) significantly inhibited the MBB in mice without influencing their locomotor activity. Further, chronic (28 days) administration of lower doses of agomelatine (10 and 20 mg/kg, i.p.) dose-dependently reduced the MBB without influencing their locomotor activity. Interaction studies revealed that pretreatment with mCPP (0.5 mg/kg, i.p.), a serotonin 5HT2C agonist, partially attenuated the anticompulsive effect of agomelatine (30 mg/kg). Further, a GABAA receptor agonist (diazepam, 1.25 mg/kg, i.p.) and antagonist (bicuculline, 1 mg/kg, i.p.) had no influence on the effects of agomelatine on MBB and locomotor activity. The doses of modulators were selected on the basis of dose-response studies. The results indicate that agomelatine has a potent anticompulsive effect that can be attributed to 5HT2C antagonism and MT1/2 agonism, and is certainly not mediated via its effects on the GABAergic system. Thus, the study adds to the growing literature on the psychopharmacological effects of agomelatine, and warrants further exploration in multiple paradigms.

Standardization of an ex vivo method for determination of intestinal permeability of drugs using everted rat intestine apparatus.

INTRODUCTION: Everted gut sac of rat intestine is a paradigm widely employed for determination of absorption kinetics of drugs along with evaluation of effects of absorption enhancers. Since its inception in 1954, it has been optimized to enhance tissue survival and use, but it still suffers the limitation of small serosal compartment size and lack of validity of single experiment. METHODS: The aim of the present work was to standardize a new ex vivo model to study drug absorption using a specially designed glass apparatus, everted segment of rat intestine, and three absorption markers [paracellular (atenolol), transcellular (metoprolol and propranolol)]. To validate a single experiment phenol red was used as non-absorbable marker. RESULTS: The mean apparent permeabilities (Papp) for the markers were found to be 0.054±0.024×10(-4)cm/s (atenolol), 0.84±0.14×10(-4)cm/s (metoprolol), and 1.64±0.16×10(-4)cm/s (propranolol); wherein data from only those experiment was used, which showed negligible absorption of phenol red. DISCUSSION: The model is simple to establish, gives excellent absorption kinetics, and most importantly provides a way to validate the experiment simultaneously. The proposed method can be used in all kinds of drug absorption studies, especially biopharmaceutical investigations studying absorption enhancement strategies.

Acquisition, expression, and reinstatement of ethanol-induced conditioned place preference in mice: effects of exposure to stress and modulation by mecamylamine.

Nicotinic acetylcholine receptors mediate some of the rewarding and motivational effects of ethanol, including relapses. Relapses are common in drug addicts during abstinence when exposure to any stressor ensues. However, the role of nicotinic acetylcholine receptors in the ethanol- and stress-induced reinstatement of ethanol-induced conditioned place preference has not yet been explored. Therefore, the present study investigated the influence of mecamylamine, a nicotinic acetylcholine receptors antagonist on acquisition, expression, and reinstatement of ethanol-induced conditioned place preference in adult male Swiss mice. The results revealed that mecamylamine (0.1-10 µg/mouse, intracerebroventricularly) dose dependently prevented the development, expression, and reinstatement of ethanol-induced conditioned place preference. Further, acute treatment with mecamylamine blocked the restraint stress and forced swim stress-induced reinstatement of ethanol-induced conditioned place preference. All of these treatments had no influence on the locomotor activity. Therefore, it is concluded that mecamylamine blocks the acquisition, expression and reinstatement of conditioned reinforcing effects of ethanol without per se reinforcing or aversive influence. This ability of mecamylamine might be a potential advantage in the treatment of alcoholism.

Protection of cholinergic and antioxidant system contributes to the effect of berberine ameliorating memory dysfunction in rat model of streptozotocin-induced diabetes.

Memory impairment induced by streptozotocin in rats is a consequence of changes in CNS that are secondary to chronic hyperglycemia, impaired oxidative stress, cholinergic dysfunction, and changes in glucagon-like peptide (GLP). Treatment with antihyperglycemics, antioxidants, and cholinergic agonists are reported to produce beneficial effect in this model. Berberine, an isoquinoline alkaloid is reported to exhibit anti-diabetic and antioxidant effect, acetylcholinesterase (AChE) inhibitor, and increases GLP release. However, no report is available on influence of berberine on streptozotocin-induced memory impairment. Therefore, we tested its influence against cognitive dysfunction in streptozotocin-induced diabetic rats using Morris water maze paradigm. Lipid peroxidation and glutathione levels as parameters of oxidative stress and choline esterase (ChE) activity as marker of cholinergic function were assessed in the cerebral cortex and hippocampus. Thirty days after diabetes induction rats showed a severe deficit in learning and memory associated with increased lipid peroxidation, decreased reduced glutathione, and elevated ChE activity. In contrast, chronic treatment with berberine (25-100mg/kg, p.o., twice daily, 30 days) improved cognitive performance, lowered hyperglycemia, oxidative stress, and ChE activity in diabetic rats. In another set of experiment, berberine (100mg/kg) treatment during training trials also improved learning and memory, lowered hyperglycemia, oxidative stress, and ChE activity. Chronic treatment (30 days) with vitamin C or metformin, and donepezil during training trials also improved diabetes-induced memory impairment and reduced oxidative stress and/or choline esterase activity. In conclusion, the present study demonstrates treatment with berberine prevents the changes in oxidative stress and ChE activity, and consequently memory impairment in diabetic rats.

NSAIDs-Related Pyloroduodenal Obstruction and Its Endoscopic Management.

Endoscopic balloon dilatation (EBD) has important role in the management of benign gastric outlet obstruction. Although there are many reports on the role of EBD in the management of corrosive-induced and peptic benign GOO, there is scanty data on its role in the management of NSAID-induced GOO. We report 10 cases of NSAID-induced pyloroduodenal obstruction and their endoscopic management. The most common site of involvement was duodenum (5/10) followed by both pylorus and duodenum (4/10) and pylorus (1/10). Most of the strictures were short web-like, and the mean (SD) number of stricture was 2.0 (0.94). Endoscopic balloon dilatation was successful in 90% (9/10) cases requiring mean (SD) of 2.0 (1.6) sessions of dilatation to achieve target diameter of 15 mm and mean (SD) of 5.3 (2.7) sessions to maintain it over a treatment period of 4.5 months (IQR 2-15 months). There was no procedure-related complication or mortality.

Inhibitory effect of berberine on the motivational effects of ethanol in mice.

It is believed that drug-induced rewarding effects play an important role in the development of substance dependence. Recently, berberine was reported to inhibit the rewarding effects of drugs of abuse such as cocaine, morphine, and nicotine. Berberine is also demonstrated to modulate the activity of several neurotransmitter systems like, dopamine, nitric oxide, serotonin, and NMDA, which are implicated in rewarding effects of ethanol. Hence, we hypothesized that berberine may modulate the ethanol-induced rewarding effects. Therefore, we studied the effect of berberine on locomotor sensitization, conditioned place preference (CPP), and ethanol drinking preference in mice. The results revealed that acute administration of berberine (2.5, 5, and 10 mg/kg, i.p.) dose dependently reduced locomotor stimulant effect of acute ethanol and expression of sensitization to locomotor stimulant effect of ethanol. Further, pretreatment with berberine (2.5, 5, and 10 mg/kg, i.p.) prior to each dose of ethanol, blocked the development as well as expression of sensitization to locomotor stimulant effect of ethanol. In another set of experiment, treatment with berberine (5 and 10 mg/kg, i.p.) reduced the induction and expression of ethanol-induced CPP in mice. In addition, berberine in these doses also reduced preference to ethanol drinking over water, but did not alter the general reward. In conclusion, the results of the present study revealed that berberine attenuates ethanol-induced rewarding effects in mice and that could be attributed to its neuro-modulatory action.