Effects Of Pharmacological Agents Research Articles

Comparison between Policaptil Gel Retard and Metformin by Testing of Temporal Changes in Patients with Metabolic Syndrome and Type 2 Diabetes

Introduction: Metabolic Syndrome (MS) is a pathologic condition characterized by Type 2 diabetes mellitus (T2DM), insulin resistance, abdominal obesity, hypertension, and hyperlipidemia. Until now, specific drugs such as metformin (MET) have been used to address its individual components; however, according to the recommendation of WHO, various plant extracts might be used as alternative medicines due to the side effects of pharmacologic agents. Policaptil Gel Retard® (PGR), a macromolecule complex based on polysaccharides which slows down the absorption rates of carbohydrates and fats, proved effective against glucose abnormalities. Our study aimed to verify the short-term efficacy and safety of PGR under real-life conditions. Methods: We evaluated both the 6-month changes in metabolic parameters in Italian patients with MS and T2DM, and the 10-year CV risk score (10-y-CV-RS) from the CUORE equation, competitively randomized to Policaptil Gel Retard (2172 mg before each main meal); Group A, n = 75, or Metformin (1500–2000 mg/day equally divided between the two main meals), and Group B, n = 75. Results: Fasting plasma glucose and HbA1c decreased significantly and similarly (p < 0.001) in the two groups. A significant decrease in BMI (−20% in the PGR group (p < 0.01), −14.3% in the MET group (p < 0.05)), % visceral fat, and UA levels was also apparent in both groups (p < 0.01). The opposite occurred for lipid profile, which improved significantly in the PGR group but remained unchanged in the MET group. Consequently, only the PGR group experienced a significant decrease in the 10-y-CV-RS (31.4 ± 8.0 vs. 19.7 ± 5.2, p < 0.0001), whereas this remained unchanged in the MET group (32.2 ± 3.3 vs. 30.5 ± 8.7; p n.s.). Conclusions: PGR could represent a suitable alternative to MET as a first-line treatment option, especially now that an ever-increasing number of people prefer natural products based on plant extracts. This is particularly pertinent given that, besides trying to avoid gastrointestinal side-effects as much as possible, patients might be sensitive to ecotoxicology-related problems involving plants and animals caused by the worldwide spread of environmental MET metabolites.

INVESTIGATION OF THE IMMUNOTOXIC PROPERTIES OF STRAWBERRY GARDEN LEAF EXTRACT DRY

Abstract: The main task of the preclinical study of the effect of potential drugs on the immune system is to prove or exclude the possibility of developing an immunotoxic effect caused by a pharmacological agent or its metabolites in an animal experiment. The proposed approach to assessing the immunotoxic effect of pharmacological agents consists in the study of a number of integral immunological functions that allow, taking into account the results of hematological and morphological studies of lymphoid organs, to assess the possible risk when using a new pharmacological agent. Mandatory testing for immunotoxicity should be subject to new, original pharmacological agents, as well as well-known drugs for which there is no data on the study of immunotoxicity, recommended for use in long repeated courses; use in pediatric practice, as well as for the treatment of pregnant women and when prescribed during lactation; as prophylactic agents and contraceptives; for use without a doctor's appointment among the general population [2,3]. Strawberry garden leaf extract dry (strawberry garden extract) is one of the potential substances for obtaining safe medicines for the prevention and treatment of diseases of the urinary tract, as it has diuretic and anti-inflammatory activity [4]. The study of the immunotoxic properties of strawberry garden extract is an obligatory part of the preclinical safety assessment of a new pharmacological substance for obtaining safe medicines with it. In this regard, studies on the study of the immunotoxic properties of strawberry leaves of dry extract in the framework of preclinical studies and substantiation of the use of the substance for the further development of medicines based on it are relevant.

Sterile water injections for relief of labour pain (the SATURN trial): study protocol for a randomised controlled trial

BackgroundUp to 80% of women use some form of pharmacological analgesia during labour and birth. The side effects of pharmacological agents are often incompatible with the concurrent use of non-pharmacological pain relieving strategies, such as water immersion, ambulation and upright positioning, or may have negative effects on both the mother and fetus. Sterile water injections given into the skin of the lumbar region have been demonstrated to reduce back pain during labour. However, the injections given for back pain have no effect on abdominal contraction pain. The analgesic efficacy of sterile water injections for abdominal pain during childbirth is unknown. The injections cause an immediate, brief but significant pain that deters some women from using the procedure. This study aims to investigate the use of water injections given intradermally into the abdomen to relieve labour contraction pain. A vapocoolant spray will be applied to the skin immediately prior to the injections to reduce the injection pain.MethodsIn this pragmatic, placebo controlled trial 154 low-risk women in labour at term with a labour pain score ≥ 60 on a 100 millimitre visual analogue scale (VAS) will be randomly allocated to receive either six injections of sterile water or a sodium chloride 0.9% solution as a placebo (0.1–.0.3 ml per injection). Three injections are given along the midline from the fundus to the supra-pubis and three laterally across the supra-pubis. The primary outcome will be the difference in VAS score 30 min post injection between groups. Secondary outcomes include VAS score of the injection pain on administration, VAS score of labour pain at 60 and 90 min, maternal and neonatal birth outcomes.DiscussionAccess to effective pain relief during labour is fundamental to respectful and safe maternity care. Pharmacological analgesics should support rather than limit other non-pharmacological strategies. Sterile water injections have the potential to provide an alternative form of labour pain relief that is easy to administer in any labour and birth setting, and compatible with other non-pharmacological choices.Trial registrationANZCTR (ACTRN12621001036808) Date submitted: 22/06/2021. Date registered: 05/08/2021. https://www.anzctr.org.au/

No benefit of vorapaxar on walking performance in patients with intermittent claudication.

Background: The effect of pharmacologic agents in improving walking and quality of life measures in patients with intermittent claudication (IC) is variable. The objective of this study was to investigate the effect of the novel antithrombotic vorapaxar on symptom status in patients with IC. Methods: The study was a multicenter, randomized, placebo-controlled trial wherein patients with IC were treated with either vorapaxar or placebo in addition to a home exercise program for 6 months. Walking performance and quality of life were assessed by graded treadmill test (GTT) and 12-Item Short-Form Survey (SF-12), respectively, at baseline and at 6 months. A total of 102 subjects were randomized across 12 centers. Results: Of the subjects randomized, 66 completed all study assessments and comprised the dataset that was analyzed. After 6 months, there was no significant difference between the vorapaxar and placebo groups in walking performance, as reflected by the GTT, or in quality of life, as reflected by the SF-12. There were no severe bleeding events in either group. Conclusion: This study found no benefit of vorapaxar in patients with IC and reiterates the need for future drug therapy studies that expand the benefits of supervised exercise therapy in patients with IC. ClinicalTrials.gov Identifier: NCT02660866.

Anaesthetic management of dogs with myxomatous mitral valve disease

Myxomatous mitral valve disease is the most commonly acquired heart disease in the dog. Affected dogs have a reduced forward stroke volume as a result of the regurgitant flow back through the compromised mitral valve leaflets. Primary care practitioners will be all too familiar with the challenges of performing a general anaesthetic on these animals and unfortunately, there is no ideal protocol for every case. Having knowledge of the haemodynamic changes that occur with myxomatous mitral valve disease, compared to structurally normal hearts, as well as a good understanding of pharmacological effects of agents used in general anaesthesia, is essential in the safe management of these cases. This article will summarise disease pathophysiology, concurrent cardiac medications and commonly used pre-anaesthetic, induction and maintenance agents available in primary care practice for use in dogs with myxomatous mitral valve disease.

Impact of Environmental and Pharmacologic Changes on the Upper Gastrointestinal Microbiome.

Diseases of the upper gastrointestinal tract have become more prevalent over time. Mechanisms of disease formation are still only partially understood. Recent literature has shown that the surrounding microbiome affects the propensity for disease formation in various parts of the upper gastrointestinal tract. A review was performed of any literature to our best knowledge concerning the effects of pharmacologic agents, environmental changes, and surgical intervention on the microbiome of the upper gastrointestinal tract. Searches of the literature were performed using specific keywords related to drugs, surgical procedures, and environmental factors. Many prescription and nonprescription drugs that are commonly used have varying effects on the upper gastrointestinal tract. Proton pump inhibitors may affect the relative prevalence of some organisms in the lower esophagus and have less effect in the proximal esophagus. Changes in the esophageal microbiome correlate with some esophageal diseases. Drugs that induce weight loss have also been shown to affect the microbiomes of the esophagus and stomach. Common surgical procedures are associated with shifts in the microbial community in the gastrointestinal tract. Environmental factors have been shown to affect the microbiome in the upper gastrointestinal tract, as geographic differences correlate with alterations in the microbiome of the gastrointestinal tract. Understanding the association of environmental and pharmacologic changes on the microbiome of the upper gastrointestinal tract will facilitate treatment plans to reduce morbidity from disease.

Effectiveness of Pharmacological Agents and Validation of Diagnostic Scales for the Management of Paroxysmal Sympathetic Hyperactivity in Hispanics.

The identification and treatment of paroxysmal sympathetic hyperactivity (PSH) still present a significant challenge. We assessed the efficacy of pharmacological agents in treating PSH symptoms and the validity of the diagnostic scales in a cohort of Hispanic patients. A retrospective chart review of cases from a single hospital was conducted in 464 records. Exclusion criteria included underlying conditions such as severe infection. Only nine patients remained in the cohort after examining their clinical records, corresponding to the following diagnoses: traumatic brain injury, subdural hemorrhage, anoxic or ischemic encephalopathy, pneumocephalus, and cerebral palsy. Using the PSH likelihood scale, six of the nine patients were identified with a score of 17 or higher, corresponding to a “probable” PSH, and three patients obtained a score between 8 and 16, corresponding to a “possible” PSH diagnosis. The top three classes of medications used were beta-blockers, antipyretics, and opioids. Benzodiazepines and neuromodulators were also frequently used in patients with trauma, but not in the ones with non-traumatic injuries. Interestingly, 75% of the patients have prescribed levothyroxine as a home medication after the PSH presentation. Medication administration did not follow a specific pattern, suggesting high variability in the management of PSH within our setting, requiring further research. Our results suggest that the pituitary axis might be involved in the progression of PSH. Establishing a specific medical code (e.g., ICD-10) describing PSH as a single entity is essential for appropriate identification and management.

Recent Findings on the Effects of Pharmacological Agents on the Nerve Regeneration after Peripheral Nerve Injury.

Peripheral nerve injuries (PNIs) are accompanied with neuropathic pain and functional disability. Despite improvements in surgical repair techniques in recent years, the functional recovery is yet unsatisfied. Indeed a successful nerve repair depends not only on the surgical strategy but also on the cellular and molecular mechanisms involved in traumatic nerve injury. In contrast to all strategies suggested for nerve repair, pharmacotherapy is a cheap, accessible and non-invasive treatment that can be used immediately after nerve injury. This study aimed to review the effects of some pharmacological agents on the nerve regeneration after traumatic PNI evaluated by functional, histological and electrophysiological assessments. In addition, some cellular and molecular mechanisms responsible for their therapeutic actions, restricted to neural tissue, are suggested. These findings can not only help to find better strategies for peripheral nerve repair, but also to identify the neuropathic effects of various medications and their mechanisms of action.

Metformin Use in Diabetes Prior to Hospitalization: Effects on Mortality in Covid-19

Objective: Although type 2 diabetes mellitus (T2DM) has been reported as a risk factor for coronavirus disease 2019 (COVID-19), the effect of pharmacologic agents used to treat T2DM, such as metformin, on COVID-19 outcomes remains unclear. Metformin increases the expression of angiotensin converting enzyme 2, a known receptor for severe acute respiratory syndrome coronavirus 2. Data from people with T2DM hospitalized for COVID-19 were used to test the hypothesis that metformin use is associated with improved survival in this population.Methods: Retrospective analyses were performed on de-identified clinical data from a major hospital in Wuhan, China, that included patients with T2DM hospitalized for COVID-19 during the recent epidemic. One hundred and thirty-one patients diagnosed with COVID-19 and T2DM were used in this study. The primary outcome was mortality. Demographic, clinical characteristics, laboratory data, diabetes medications, and respiratory therapy data were also included in the analysis.Results: Of these 131 patients, 37 used metformin with or without other antidiabetes medications. Among the 37 metformin-taking patients, 35 (94.6%) survived and 2 (5.4%) did not survive. The mortality rates in the metformin-taking group versus the non-metformin group were 5.4% (2/37) versus 22.3% (21/94). Using multivariate analysis, metformin was found to be an independent predictor of survival in this cohort (P = .02).Conclusion: This study reveals a significant association between metformin use and survival in people with T2DM diagnosed with COVID-19. These clinical data are consistent with potential benefits of the use of metformin for COVID-19 patients with T2DM.

Diet and Lp(a): Does Dietary Change Modify Residual Cardiovascular Risk Conferred by Lp(a)?

Lipoprotein(a) [Lp(a)] is an independent, causal, genetically determined risk factor for cardiovascular disease (CVD). We provide an overview of current knowledge on Lp(a) and CVD risk, and the effect of pharmacological agents on Lp(a). Since evidence is accumulating that diet modulates Lp(a), the focus of this paper is on the effect of dietary intervention on Lp(a). We identified seven trials with 15 comparisons of the effect of saturated fat (SFA) replacement on Lp(a). While replacement of SFA with carbohydrate, monounsaturated fat (MUFA), or polyunsaturated fat (PUFA) consistently lowered low-density lipoprotein cholesterol (LDL-C), heterogeneity in the Lp(a) response was observed. In two trials, Lp(a) increased with carbohydrate replacement; one trial showed no effect and another showed Lp(a) lowering. MUFA replacement increased Lp(a) in three trials; three trials showed no effect and one showed lowering. PUFA or PUFA + MUFA inconsistently affected Lp(a) in four trials. Seven trials of diets with differing macronutrient compositions showed similar divergence in the effect on LDL-C and Lp(a). The identified clinical trials show diet modestly affects Lp(a) and often in the opposing direction to LDL-C. Further research is needed to understand how diet affects Lp(a) and its properties, and the lack of concordance between diet-induced LDL-C and Lp(a) changes.

Blockade of muscarinic receptors impairs reconsolidation of older fear memory by decreasing cholinergic neurotransmission: A study in rat model of PTSD

The age and strength of fear memory are two potential parameters that can be influenced by the impairing effects of pharmacological agents on reconsolidation of fear memory. In reconsolidation, stored information is rendered labile again after being reactivated. Pharmacological manipulations at this stage result in an inability to retrieve the fear memories, suggesting that they are erased or persistently inhibited. This fear memory impairment phenomenon can be valuable to treat post-traumatic stress disorders (PTSD). Previously β-adrenergic antagonist propranolol has been repeatedly reported to impair fear memory in the treatment of PTSD. Atropine has also shown to disrupt memory formation. The present study was therefore designed to compare the effects of atropine and propranolol on reconsolidation of older fear memory in rat model of PTSD using Pavlovian fear conditioning apparatus. For this purpose 18 rats were taken and divided into control, atropine and propranolol groups and subjected to Pavlovian fear conditioning trials in order to develop animal model of PTSD. To evaluate the reconsolidation impairment of fear memory by atropine and propranolol, short term and long term memory was tested after reactivation of fear memory in rats. The present findings demonstrate that atropine significantly decreases fear expression. These results suggest that atropine significantly reduces the strength of fear memories and may be effective in the treatment of psychiatric disorders especially in PTSD.

Effectiveness of pharmacological agents for the treatment of non-infectious scleritis: a systematic review protocol

BackgroundNon-infectious scleritis is a potentially sight-threatening condition in which the sclera, the white outer layer of the eye, becomes inflamed. Whilst scleritis can be infective, the majority of cases are due to non-infectious causes, often occurring in association with an underlying systemic autoimmune or auto-inflammatory condition. Thorough systemic work-up is crucial to identify disease aetiology and exclude infection; however, a significant proportion of disease remains idiopathic with the underlying cause unknown. Non-infectious scleritis is normally managed with systemic corticosteroid and immunosuppression, yet there is no widely agreed consensus on the most appropriate therapy, and no national or international guidelines exist for treatment of non-infectious scleritis.MethodsStandard systematic review methodology will be used to identify, select and extract data from comparative studies of pharmacological interventions used to treat patients with non-infectious scleritis. Searches of bibliographic databases (Cochrane Library, MEDLINE, CINAHL and EMBASE) and clinical trial registers will be employed. No restrictions will be placed on language or date of publication. Non-English articles will be translated where necessary. The primary outcome of interest will be disease activity measured by reduction in scleritis grading according to standardised grading systems. Secondary outcomes will include change in best corrected visual acuity, reduction in concurrent dose of systemic corticosteroid, time to treatment failure, adverse events and health-related quality of life. Risk of bias assessment will be conducted appropriate to each study design. Study selection, data extraction and risk of bias assessment will be completed by two reviewers independently. Data will be presented in a table and a narrative synthesis will be undertaken. Meta-analysis will be performed where methodological and clinical homogeneity exists. Subgroup and sensitivity analysis will be undertaken if appropriate.DiscussionMany studies have investigated the effectiveness of pharmacological agents used in the management of non-infectious scleritis. A systematic review is needed to collate and analyse this evidence. Findings of this systematic review will help guide ophthalmologists managing patients with non-infectious scleritis and may form the basis for evidence-based recommendations for future clinical practice and encourage standardisation of treatment protocols.Systematic review registrationPROSPERO CRD42019125198

Mouse Models of Myeloid Malignancies.

Mouse models of human myeloid malignancies support the detailed and focused investigation of selected driver mutations and represent powerful tools in the study of these diseases. Carefully developed murine models can closely recapitulate human myeloid malignancies in vivo, enabling the interrogation of a number of aspects of these diseases including their preclinical course, interactions with the microenvironment, effects of pharmacological agents, and the role of non-cell-autonomous factors, as well as the synergy between co-occurring mutations. Importantly, advances in gene-editing technologies, particularly CRISPR-Cas9, have opened new avenues for the development and study of genetically modified mice and also enable the direct modification of mouse and human hematopoietic cells. In this review we provide a concise overview of some of the important mouse models that have advanced our understanding of myeloid leukemogenesis with an emphasis on models relevant to clonal hematopoiesis, myelodysplastic syndromes, and acute myeloid leukemia with a normal karyotype.

ЭФФЕКТИВНОСТЬ ФАРМАКОЛОГИЧЕСКИХ СРЕДСТВ ДЛЯ СНИЖЕНИЯ НЕГАТИВНОГО ВОЗДЕЙСТВИЯ ПРИ ИНТОКСИКАЦИИ ЖИВОТНЫХ КАДМИЕМ И СВИНЦОМ

In laboratory conditions, the effectiveness of pharmacological agents in reducing the negative effects with the combined intake of cadmium and lead was studied. The following agents were studied as protectors: solvimin selenium, DAFS-25, gemovit-meyan, L-cysteine. The use of each drug separately reduced the negative effects of cadmium and lead on the body, but did not completely restore all studied parameters to the level of control and did not reduce the accumulation of heavy metals in the organs and tissues of animals. Based on the data obtained, it was concluded that the most urgent is the development of complex tools that affect different systems of the animal organism and the stages of its interaction with heavy metals.

Effect of Pharmacological Agents Administered for Attenuating the Extubation Response on the Quality of Extubation: A Systematic Review.

BackgroundSeveral drugs have been tried to obtund the hemodynamic extubation response but all have variable side effects that may affect the quality of short-term recovery.ObjectiveOur primary objective was to evaluate the effect of pharmacological agents, such as dexmedetomidine, local anesthetics, and so on, administered for attenuating the extubation response on the quality of extubation, as judged by the presence or absence of cough, sedation, and laryngospasm/bronchospasm in adult patients who had undergone general anesthesia. A secondary objective was to evaluate the effect of these drugs on other immediate post-extubation complications such as respiratory depression, desaturation, bradycardia, hypotension, and nausea and vomiting (PONV).MethodsThis is a systematic review of (randomized controlled trials) RCTs with meta-analysis. The Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for RCTs on the effect of pharmacological agents on both the hemodynamic extubation response as well as the quality of extubation.ResultsFourteen out of 24 included studies were subjected to a meta-analysis. The risk of cough was less likely in the intervention group as compared to control groups (OR 0.26, 95% CI 0.15 to 0.46, p<0.00001, I2=35%). Sedation, hypotension (OR= 10.47; 95% CI: 1.86, 58.80, p=0.008, I2=0%), and bradycardia (OR= 6.57; 95% CI: 2.09, 20.64, p=0.001, I2=0%) were reported with dexmedetomidine. Only one study reported laryngospasm with dexmedetomidine and two studies with opioids.ConclusionDexmedetomidine 0.4 to 0.5 ug/kg was associated with smooth extubation, minimal coughing, no laryngospasm/ bronchospasm, and with stable hemodynamics, without causing respiratory depression, PONV, and desaturation. However, in higher doses (more than 0.5 ug/kg), it caused bradycardia, hypotension, and sedation. Other pharmacological agents, such as local anesthetics, calcium channel blockers, and opioids, did not attenuate cough associated with extubation.

Measurement of Retinal Microvascular Blood Velocity Using Erythrocyte Mediated Velocimetry

Changes in retinal blood flow may be involved in the pathogenesis of glaucoma and other ocular diseases. Erythrocyte mediated velocimetry (EMV) is a novel technique where indocyanine green (ICG) dye is sequestered in erythrocyte ghosts and autologously re-injected to allow direct visualization of erythrocytes for in vivo measurement of speed. The purpose of this study is to determine the mean erythrocyte speed in the retinal microvasculature, as well as the intravisit and intervisit variability of EMV. Data from 23 EMV sessions from control, glaucoma suspect, and glaucoma patients were included in this study. In arteries with an average diameter of 43.11 µm ± 6.62 µm, the mean speed was 7.17 mm/s ± 2.35 mm/s. In veins with an average diameter of 45.87 µm ± 12.04 µm, the mean speed was 6.05 mm/s ± 1.96 mm/s. Intravisit variability, as measured by the mean coefficient of variation, was 3.57% (range 0.44–9.68%). Intervisit variability was 4.85% (range 0.15–8.43%). EMV may represent reliable method for determination of retinal blood speed, potentially allowing insights into the effects of pharmacologic agents or pathogenesis of ocular diseases.

What are the effects of pharmacological agents for adults with acute respiratory distress syndrome (ARDS)?

What are the effects of pharmacological agents for adults with acute respiratory distress syndrome (ARDS)?

Abnormal neural functions associated with motor inhibition deficits in schizophrenia and bipolar disorder.

Deficits in response inhibition have been observed in schizophrenia and bipolar disorder; however, the neural origins of the abnormalities and their relevance to genetic liability for psychosis are unknown. We used a stop‐signal task to examine motor inhibition and associated neural processes in schizophrenia patients (n = 57), bipolar disorder patients (n = 21), first‐degree biological relatives of patients with schizophrenia (n = 34), and healthy controls (n = 56). Schizophrenia patients demonstrated motor control deficits reflected in longer stop‐signal reaction times and elongated reaction times. With the possibility of needing to inhibit a button press, both schizophrenia and bipolar disorder patients showed diminished reductions of the P300 brain response and only the healthy controls demonstrated adjustments in response execution time, as measured by response‐locked lateralized readiness potentials. Schizotypal traits in the biological relatives were associated with less P300 modulation consistent with the motor‐related anomalies being associated with subtle schizophrenia‐spectrum symptomatology in family members. The two patient groups had elongated response selection processes as manifest in the delayed onset of the stimulus‐locked lateralized readiness potential. The bipolar disorder group was unique in showing significantly diminished neural responses to the stop‐signal to inhibit a response. Antipsychotic medication dosage was related to worse motor inhibition, thus motor inhibition deficits in schizophrenia may be partially explained by the effect of pharmacological agents. Failed modulation of brain processes in relation to response inhibition probability and the lengthening of motor response selection appear to be transdiagnostic abnormalities spanning schizophrenia and bipolar disorder.

Impact of modulation of the α7 nicotinic acetylcholine receptor on nicotine reward in the mouse conditioned place preference test.

The α7 nicotinic acetylcholine receptor (nAChR) has been implicated as a target in modulating nicotine reward. However, the effect of pharmacological agents that have been shown to alter the channel properties of the α7 nAChR is not well understood in nicotine reward. This study aimed to investigate the impact of α7 nAChR pharmacological modulation on nicotine conditioned place preference (CPP) in mice by using positive allosteric modulators (PAMs) and a silent agonist. The effect of the orthosteric α7 nAChR full agonist PNU282987 (1.3 and 9mg/kg, s.c.), Type I α7 PAM NS1738 (1 and 10mg/kg; i.p.), the Type II α7 PAM PNU120596 (0.3, 1, and 3mg/kg, i.p.), and the α7 silent agonist NS6740 (1 and 3mg/kg, i.p) on nicotine CPP was measured in mice. Mice were conditioned with either saline or nicotine (0.5mg/kg) for 3days in the CPP paradigm. The α7 full orthosteric agonist PNU282987 and the Type II α7 nAChR PAM PNU120596 reduced nicotine CPP, while the silent agonist NS6740 and Type I PAM NS1738 had no effect. The effects of PNU282987 and PNU120596 did not have an effect on morphine CPP. Taken together, our results suggest that modulation of the α7 nAChR can play important roles in nicotine CPP in mice. In addition, the Type II α7 nAChR PAM PNU120596 attenuated nicotine reward suggesting that endogenous acetylcholine/choline tone is sufficient to reduce nicotine CPP. These findings highlight a beneficial effect of using α7 nAChR PAMs in nicotine reward.

Characterization at the Molecular Level using Robust Biochemical Approaches of a New Kinase Protein.

Extensive whole genome sequencing has identified many Open Reading Frames (ORFs) providing many potential proteins. These proteins may have important roles for the cell and may unravel new cellular processes. Among proteins, kinases are major actors as they belong to cell signaling pathways and have the ability to switch on or off many processes crucial to the fate of the cell, such as cell growth, division, differentiation, motility, and death. In this study, we focused on a new potential kinase protein, LIMK2-1. We demonstrated its existence by Western Blot using a specific antibody. We evaluated its interaction with an upstream regulating protein using coimmunoprecipitation experiments. Coimmunoprecipitation is a very powerful technique able to detect the interaction between two target proteins. It may also be used to detect new partners of a bait protein. The bait protein may be purified either via a tag engineered to its sequence or via an antibody specifically targeting it. These protein complexes may then be separated by SDS-PAGE (Sodium Dodecyl Sulfate PolyAcrylamide Gel) and identified using mass spectrometry. Immunoprecipitated LIMK2-1 was also used to test its kinase activity in vitro by γ[32P] ATP labeling. This well-established assay may use many different substrates, and mutated versions of the bait may be used to assess the role of specific residues. The effects of pharmacological agents may also be evaluated since this technique is both highly sensitive and quantitative. Nonetheless, radioactivity handling requires particular caution. Kinase activity may also be assessed with specific antibodies targeting the phospho group of the modified amino acid. These kinds of antibodies are not commercially available for all the phospho modified residues.