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Microbiological Research Mar 2024Aminophosphonates, like glyphosate (GS) or metal chelators such as ethylenediaminetetra(methylenephosphonic acid) (EDTMP), are released on a large scale worldwide. Here,...
Aminophosphonates, like glyphosate (GS) or metal chelators such as ethylenediaminetetra(methylenephosphonic acid) (EDTMP), are released on a large scale worldwide. Here, we have characterized a bacterial strain capable of degrading synthetic aminophosphonates. The strain was isolated from LC/MS standard solution. Genome sequencing indicated that the strain belongs to the genus Ochrobactrum. Whole-genome classification using pyANI software to compute a pairwise ANI and other metrics between Brucella assemblies and Ochrobactrum contigs revealed that the bacterial strain is designated as Ochrobactrum sp. BTU1. Degradation batch tests with Ochrobactrum sp. BTU1 and the selected aminophosphonates GS, EDTMP, aminomethylphosphonic acid (AMPA), iminodi(methylene-phosphonic) (IDMP) and ethylaminobis(methylenephosphonic) acid (EABMP) showed that the strain can use all phosphonates as sole phosphorus source during phosphorus starvation. The highest growth rate was achieved with AMPA, while EDTMP and GS were least supportive for growth. Proteome analysis revealed that GS degradation is promoted by C-P lyase via the sarcosine pathway, i.e., initial cleavage at the C-P bond. We also identified C-P lyase to be responsible for degradation of EDTMP, EABMP, IDMP and AMPA. However, the identification of the metabolite ethylenediaminetri(methylenephosphonic acid) via LC/MS analysis in the test medium during EDTMP degradation indicates a different initial cleavage step as compared to GS. For EDTMP, it is evident that the initial cleavage occurs at the C-N bond. The detection of different key enzymes at regulated levels, form the bacterial proteoms during EDTMP exposure, further supports this finding. This study illustrates that widely used and structurally more complex aminophosphonates can be degraded by Ochrobactrum sp. BTU1 via the well-known degradation pathways but with different initial cleavage strategy compared to GS.
Topics: Ochrobactrum; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Biodegradation, Environmental; Glyphosate; Organophosphonates; Phosphorus; Phentermine
PubMed: 38211497
DOI: 10.1016/j.micres.2024.127600 -
Current Obesity Reports Mar 2024This review provides an overview of the history, mechanism of action, and expected treatment effects of the anti-obesity medication (AOM), phentermine. It also includes... (Review)
Review
PURPOSE OF REVIEW
This review provides an overview of the history, mechanism of action, and expected treatment effects of the anti-obesity medication (AOM), phentermine. It also includes a summary of recent research and practical guidance for prescribing clinicians.
RECENT FINDINGS
Recent research on phentermine is sparse and consists primarily of observational studies with methodologic limitations. These studies suggest that phentermine use is associated with clinically significant weight loss in adults and that the medication is generally well tolerated. Large-scale observational studies evaluating phentermine's safety have not identified an increased risk of cardiovascular events or elevations in blood pressure. There is no data to support the notion that phentermine is addictive. Although it remains the most commonly prescribed AOM in the USA, phentermine has little rigorous research to support its efficacy and safety in long-term treatment, which creates a dilemma with guideline-recommended chronic use of AOMs. While we await forthcoming conclusive data on this front, clinicians may consider using phentermine long-term in selected patients, if such prescribing is consistent with local regulatory statutes.
Topics: Adult; Humans; Anti-Obesity Agents; Obesity; Phentermine
PubMed: 38172485
DOI: 10.1007/s13679-023-00546-9 -
Alimentary Pharmacology & Therapeutics Feb 2024Obesity has reached epidemic proportions, with >40% of the US population affected. Although traditionally managed by lifestyle modification, and less frequently by... (Review)
Review
BACKGROUND
Obesity has reached epidemic proportions, with >40% of the US population affected. Although traditionally managed by lifestyle modification, and less frequently by bariatric therapies, there are significant pharmacological advancements.
AIMS
To conduct a narrative review of the neurohormonal and physiological understanding of weight gain and obesity, and the development, clinical testing, indications, expected clinical outcomes, and associated risks of current FDA-approved and upcoming anti-obesity medications (AOMs).
METHODS
We conducted a comprehensive review in PubMed for articles on pathophysiology and complications of obesity, including terms 'neurohormonal', 'obesity', 'incretin', and 'weight loss'. Next, we searched for clinical trial data of all FDA-approved AOMs, including both the generic and trade names of orlistat, phentermine/topiramate, bupropion/naltrexone, liraglutide, and semaglutide. Additional searches were conducted for tirzepatide and retatrutide - medications expecting regulatory approval. Searches included combinations of terms related to mechanism of action, indications, side effects, risks, and future directions.
RESULTS
We reviewed the pathophysiology of obesity, including specific role of incretins and glucagon. Clinical data supporting the use of various FDA-approved medications for weight loss are presented, including placebo-controlled or, when available, head-to-head trials. Beneficial metabolic effects, including impact on liver disease, adverse effects and risks of medications are discussed, including altered gastrointestinal motility and risk for periprocedural aspiration.
CONCLUSION
AOMs have established efficacy and effectiveness for weight loss even beyond 52 weeks. Further pharmacological options, such as dual and triple incretins, are probable forthcoming additions to clinical practice for combating obesity and its metabolic consequences such as metabolic dysfunction-associated steatotic liver disease.
Topics: Humans; Incretins; Topiramate; Fructose; Obesity; Anti-Obesity Agents; Weight Loss; Liver Diseases
PubMed: 38169126
DOI: 10.1111/apt.17856 -
Obesity (Silver Spring, Md.) Mar 2024The study's objective was to examine the percentage of patients with an initial antiobesity medication (AOM) fill who were persistent with AOM at 3, 6, and 12 months...
OBJECTIVE
The study's objective was to examine the percentage of patients with an initial antiobesity medication (AOM) fill who were persistent with AOM at 3, 6, and 12 months and to characterize factors associated with persistence at 12 months.
METHODS
This retrospective cohort study used electronic health records from January 2015 to July 2023 in a large health system in Ohio and Florida and included adults with BMI ≥30 kg/m who had an initial AOM prescription filled between 2015 and 2022.
RESULTS
The authors identified 1911 patients with a median baseline BMI of 38 (IQR, 34-44). Over time, 44% were persistent with AOM at 3 months, 33% at 6 months, and 19% at 12 months. Across categories of AOM, the highest 1-year persistence was in patients receiving semaglutide (40%). Semaglutide (adjusted odds ratio [AOR] = 4.26, 95% CI: 3.04-6.05) was associated with higher odds of 1-year persistence, and naltrexone-bupropion (AOR = 0.68, 95% CI: 0.46-1.00) was associated with lower odds, compared with phentermine-topiramate. Among patients who were persistent at 6 months, a 1% increase in weight loss at 6 months was associated with 6% increased odds of persistence at year 1 (AOR = 1.06, 95% CI: 1.03-1.09).
CONCLUSIONS
Later-stage persistence with AOM varies considerably based on the drug and the weight loss at 6 months.
Topics: Adult; Humans; Retrospective Studies; Anti-Obesity Agents; Weight Loss; Ohio
PubMed: 38053443
DOI: 10.1002/oby.23952 -
Methods in Molecular Biology (Clifton,... 2024We hereby present a fast and high-throughput LC-MS/MS assay for the simultaneous analysis of amphetamines and cocaine in human urine. The assay is used for confirmations...
We hereby present a fast and high-throughput LC-MS/MS assay for the simultaneous analysis of amphetamines and cocaine in human urine. The assay is used for confirmations following immunoassay urine drug screens as well as a quantitative assay to report actual urine concentrations in the range 30-10,000 ng/mL for each of the seven analytes, namely, amphetamine; methamphetamine; phentermine; methylenedioxyamphetamine; 3,4-methylenedioxymethamphetamine; methylenedioxy-ethyl-amphetamine; and a cocaine metabolite, benzoylecgonine. The assay derives its efficacy from minimal sample preparation via dilute and shoot. The platform is based on reversed-phase liquid chromatography coupled to the TSQ Endura triple-quadrupole (QqQ) MS instrument for detection via electrospray ionization multiple-reaction monitoring MS. The quantitative analysis is based on the linear calibration whereby the instrument response for each analyte at a given concentration is normalized against stable isotope-labeled internal standard. In addition, the assay can be multiplexed across more than one LC channel to obtain high-sample throughput.
Topics: Humans; Chromatography, Liquid; Tandem Mass Spectrometry; Substance Abuse Detection; Amphetamines; Amphetamine; Cocaine; Reproducibility of Results
PubMed: 38036806
DOI: 10.1007/978-1-0716-3541-4_2 -
Cureus Oct 2023To evaluate the effect of common weight loss pharmacotherapies among low-income, racially diverse adult patients at an urban safety-net weight management clinic.
OBJECTIVE
To evaluate the effect of common weight loss pharmacotherapies among low-income, racially diverse adult patients at an urban safety-net weight management clinic.
METHODS
Our retrospective review from 2015 to 2019 examined patients who took either GLP-1 analog (GL) or phentermine/topiramate (PT) for ≥90 days and patients who exclusively pursued non-pharmacologic treatment for comparison. Changes in weight, blood pressure, and hemoglobin A1c at 1-year follow-up were reported.
RESULTS
We analyzed 22 GL and 26 PT patients and included 40 patients who pursued only lifestyle modifications (LM). All three groups achieved significant weight loss at one year: GL -3.69 (interquartile range (IQR): -11.0, -1.77) kg (p=0.0004), PT -7.01 (IQR: -13.4, -1.45) kg (p<0.001), and LM -3.01 (IQR: -6.81, 1.13) kg (p=0.005). There was no significant difference in the median weight loss (p=0.11) between the three groups. We observed no significant changes in systolic blood pressure but saw a significant change of -0.75 in hemoglobin A1c (IQR: -1.35, -0.25) (p=0.01) among patients with diabetes in the GL group.
CONCLUSIONS
Our real-world applications of GLP-1 and phentermine/topiramate suggest that both are effective weight loss medication regimens in low-socioeconomic status patients.
PubMed: 38034269
DOI: 10.7759/cureus.47922 -
JAMA Nov 2023Obesity affects approximately 42% of US adults and is associated with increased rates of type 2 diabetes, hypertension, cardiovascular disease, sleep disorders,... (Review)
Review
IMPORTANCE
Obesity affects approximately 42% of US adults and is associated with increased rates of type 2 diabetes, hypertension, cardiovascular disease, sleep disorders, osteoarthritis, and premature death.
OBSERVATIONS
A body mass index (BMI) of 25 or greater is commonly used to define overweight, and a BMI of 30 or greater to define obesity, with lower thresholds for Asian populations (BMI ≥25-27.5), although use of BMI alone is not recommended to determine individual risk. Individuals with obesity have higher rates of incident cardiovascular disease. In men with a BMI of 30 to 39, cardiovascular event rates are 20.21 per 1000 person-years compared with 13.72 per 1000 person-years in men with a normal BMI. In women with a BMI of 30 to 39.9, cardiovascular event rates are 9.97 per 1000 person-years compared with 6.37 per 1000 person-years in women with a normal BMI. Among people with obesity, 5% to 10% weight loss improves systolic blood pressure by about 3 mm Hg for those with hypertension, and may decrease hemoglobin A1c by 0.6% to 1% for those with type 2 diabetes. Evidence-based obesity treatment includes interventions addressing 5 major categories: behavioral interventions, nutrition, physical activity, pharmacotherapy, and metabolic/bariatric procedures. Comprehensive obesity care plans combine appropriate interventions for individual patients. Multicomponent behavioral interventions, ideally consisting of at least 14 sessions in 6 months to promote lifestyle changes, including components such as weight self-monitoring, dietary and physical activity counseling, and problem solving, often produce 5% to 10% weight loss, although weight regain occurs in 25% or more of participants at 2-year follow-up. Effective nutritional approaches focus on reducing total caloric intake and dietary strategies based on patient preferences. Physical activity without calorie reduction typically causes less weight loss (2-3 kg) but is important for weight-loss maintenance. Commonly prescribed medications such as antidepressants (eg, mirtazapine, amitriptyline) and antihyperglycemics such as glyburide or insulin cause weight gain, and clinicians should review and consider alternatives. Antiobesity medications are recommended for nonpregnant patients with obesity or overweight and weight-related comorbidities in conjunction with lifestyle modifications. Six medications are currently approved by the US Food and Drug Administration for long-term use: glucagon-like peptide receptor 1 (GLP-1) agonists (semaglutide and liraglutide only), tirzepatide (a glucose-dependent insulinotropic polypeptide/GLP-1 agonist), phentermine-topiramate, naltrexone-bupropion, and orlistat. Of these, tirzepatide has the greatest effect, with mean weight loss of 21% at 72 weeks. Endoscopic procedures (ie, intragastric balloon and endoscopic sleeve gastroplasty) can attain 10% to 13% weight loss at 6 months. Weight loss from metabolic and bariatric surgeries (ie, laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass) ranges from 25% to 30% at 12 months. Maintaining long-term weight loss is difficult, and clinical guidelines support the use of long-term antiobesity medications when weight maintenance is inadequate with lifestyle interventions alone.
CONCLUSION AND RELEVANCE
Obesity affects approximately 42% of adults in the US. Behavioral interventions can attain approximately 5% to 10% weight loss, GLP-1 agonists and glucose-dependent insulinotropic polypeptide/GLP-1 receptor agonists can attain approximately 8% to 21% weight loss, and bariatric surgery can attain approximately 25% to 30% weight loss. Comprehensive, evidence-based obesity treatment combines behavioral interventions, nutrition, physical activity, pharmacotherapy, and metabolic/bariatric procedures as appropriate for individual patients.
Topics: Adult; Female; Humans; Male; Anti-Obesity Agents; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Gastric Balloon; Glucagon-Like Peptide 1; Glucose; Hypertension; Obesity; Obesity Management; Overweight; Peptides; United States; Weight Loss; Body Mass Index
PubMed: 38015216
DOI: 10.1001/jama.2023.19897 -
Life (Basel, Switzerland) Nov 2023This review delves into the therapeutic applications of amphetamine-type stimulants such as lisdexamphetamine dimesylate, mixed amphetamine salts,... (Review)
Review
This review delves into the therapeutic applications of amphetamine-type stimulants such as lisdexamphetamine dimesylate, mixed amphetamine salts, 3,4-methylenedioxymethamphetamine (MDMA), dextroamphetamine, and phentermine. These compounds have been investigated for their potential in treating a range of psychiatric disorders, including attention deficit hyperactivity disorder (ADHD), drug dependence, post-traumatic stress disorder (PTSD), and obesity. Lisdexamphetamine dimesylate has shown promise in effectively treating ADHD symptoms in both children and adults. Additionally, it has been explored as a potential treatment for drug dependency and withdrawal, demonstrating encouraging results. Mixed amphetamine salts have also exhibited efficacy in reducing ADHD symptoms in adults. Future research should explore their potential use in treating bipolar disorder and cocaine dependence, considering the associated risks and benefits. MDMA-assisted psychotherapy has emerged as an innovative approach to treating PTSD, leading to sustained reductions in symptoms and even promoting post-traumatic growth. Furthermore, it has shown promise in managing anxiety related to life-threatening illnesses. Dextroamphetamine and phentermine have demonstrated efficacy in treating cocaine and opioid dependence, ADHD, and obesity. However, careful consideration and monitoring by medical professionals are essential due to the potential risks and benefits associated with them. In conclusion, amphetamine-type stimulants present a promising avenue for therapeutic interventions in various psychiatric conditions. Nevertheless, further research is necessary to comprehensively understand their mechanisms of action, dosage requirements, and long-term effects in different patient populations.
PubMed: 38004320
DOI: 10.3390/life13112180 -
Obesity Research & Clinical Practice 2023Bariatric surgery has been suggested as a safe and effective way to treat obesity by facilitating weight loss, but factors that predict the likelihood of bariatric...
BACKGROUND
Bariatric surgery has been suggested as a safe and effective way to treat obesity by facilitating weight loss, but factors that predict the likelihood of bariatric surgery are unknown. The objective of this study was to describe factors associated with individuals with obesity that influence their decision to undergo bariatric surgery.
SUBJECTS AND METHODS
The study design was a cross-sectional study and participants were recruited via a survey link posted on the Obesity Action Coalition website. Demographic data, medical data, weight loss program data, and reports of personal experiences were gathered via an online survey. A multivariate logistic regression model was conducted to examine predictors associated with bariatric surgery (N = 4192).
RESULTS
Participants who took phentermine (OR=2.983), Phentermine-topiramate (Qsymia) (OR=2.863), Naltrexone-bupropion (Contrave) (OR=3.246), or Liraglutide (Saxenda) (OR=2.144) had a higher likelihood of undergoing bariatric surgery for weight loss. Participants with type 2 diabetes (OR=1.728), post-traumatic stress disorder (PTSD) (OR=1.489), or COVID-19 (OR=3.852) had a higher likelihood of undergoing bariatric surgery while sleep apnea (OR=0.760) was associated with a lower likelihood of receiving surgery. Those who used MyFitnessPal™ (OR=2.232), Noom™ (OR=1.400), Jenny Craig™ (OR=1.533), or Keto (OR=1.664) for weight loss had a higher likelihood of obtaining bariatric surgery. Personal trauma experiences of sexual abuse (OR=1.982) and physical abuse (OR=1.490) were more associated with participants who underwent surgery.
CONCLUSIONS
A variety of characteristics were associated with decisions to undergo bariatric surgery. These findings may help to determine ways to support individuals who are considering bariatric surgery.
Topics: Humans; Anti-Obesity Agents; Diabetes Mellitus, Type 2; Cross-Sectional Studies; Obesity; Bariatric Surgery; Phentermine; Weight Loss; Obesity, Morbid
PubMed: 38000977
DOI: 10.1016/j.orcp.2023.11.003 -
Biomedicine & Pharmacotherapy =... Dec 2023Intracranial self-stimulation (ICSS) of the medial forebrain bundle in mice is an experimental model use to assess the relative potential of reward-seeking behaviors....
Abused drug-induced intracranial self-stimulation is correlated with the alteration of dopamine transporter availability in the medial prefrontal cortex and nucleus accumbens of mice.
Intracranial self-stimulation (ICSS) of the medial forebrain bundle in mice is an experimental model use to assess the relative potential of reward-seeking behaviors. Here, we used the ICSS model to evaluate the abuse potential of 18 abused drugs: 3-Fluoroethamphetamine (3-FEA); methylphenidate; cocaine; dextroamphetamine; alpha-Pyrrolidinobutyrophenone (α-PBT); 4'-Fluoro-4-methylaminorex (4-FPO); methamphetamine; larocaine; phentermine; paramethoxymethamphetamine (PMMA); phendimetrazine; N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48); Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (CB-13); 4-Ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210); Naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018); N-(ortho-methoxybenzyl)-4-ethylamphetamine (4-EA-NBOMe); N-[(2-Methoxyphenyl)methyl]-N-methyl-1-(4-methylphenyl)propan-2-amine (4-MMA-NBOMe); and 1-[1-(4-methoxyphenyl)cyclohexyl]piperidine (4-MeO-PCP). We determined dopamine transporter (DAT) availability in the medial prefrontal cortex (mPFC), striatum, and nucleus accumbens (NAc) after drug treatment. DAT availability in the mPFC and NAc significantly correlated with the ICSS threshold after drug treatment. Extracellular dopamine and calcium levels in PC-12 cells were measured following drug treatment. After drug treatment, Spearman rank and Pearson correlation analyses showed a significant difference between the extracellular dopamine level and the ICSS threshold. After drug treatment, Spearman rank correlation analysis showed a significant correlation between Ca signaling and the ICSS threshold. A positive correlation exists between the ICSS threshold and DAT availability in the mPFC and NAc provoked by abused drugs. The relative potential of drug-induced reward-seeking behavior may be related to DAT availability-mediated extracellular dopamine levels in the mPFC and NAc.
Topics: Animals; Mice; Dopamine; Dopamine Plasma Membrane Transport Proteins; Nucleus Accumbens; Prefrontal Cortex; Self Stimulation
PubMed: 37948992
DOI: 10.1016/j.biopha.2023.115860