-
ACS Sensors Sep 2018Being a typical copper-containing oxidase, tyrosinase plays critical roles in biological activity, and its aberrant expression might cause diverse skin diseases. Herein,...
Being a typical copper-containing oxidase, tyrosinase plays critical roles in biological activity, and its aberrant expression might cause diverse skin diseases. Herein, we, for the first time, have found an interesting green fluorogenic reaction between methyldopa and ethanolamine. By combining transmission electron microscopy, UV-vis absorption spectroscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and MALDI-TOF mass spectrum analysis, we have confirmed that there is a reliable method for preparing the bright green fluorescent polymethyldopa nanoparticles (PMNPs) by simply mixing methyldopa and ethanolamine at room temperature. Inspired by such a simple and convenient fluorogenic reaction, a novel polymethyldopa nanoparticles-based fluorescent sensor for detection of tyrosinase activity was developed by using the commercially available metyrosine as a substrate, accompanied by the tyrosinase-catalyzed specific conversion of metyrosine into methyldopa. According to the intrinsic sensitivity/selectivity of fluorescence technology and unambiguous response mechanism, our fluorescent sensor exhibits excellent sensing performance and can be utilized in the determination of the tyrosinase activity in real biological samples and inhibitor screening.
Topics: Enzyme Assays; Enzyme Inhibitors; Ethanolamine; Fluorescence; Fluorescent Dyes; Indoles; Methyldopa; Monophenol Monooxygenase; Nanoparticles; Polymerization; Polymers; Pyrones; Spectrometry, Fluorescence; alpha-Methyltyrosine
PubMed: 30149701
DOI: 10.1021/acssensors.8b00684 -
European Journal of Neurology Dec 2023The NKX2-1-related disorders (NKX2-1-RD) is a rare disorder characterized by choreiform movements along with respiratory and endocrine abnormalities. The European... (Review)
Review
BACKGROUND
The NKX2-1-related disorders (NKX2-1-RD) is a rare disorder characterized by choreiform movements along with respiratory and endocrine abnormalities. The European Reference Network of Rare Neurological Disorders funded by the European Commission conducted a systematic review to assess drug treatment of chorea in NKX2-1-RD, aiming to provide clinical recommendations for its management.
METHODS
A systematic pairwise review using various databases, including MEDLINE, Embase, Cochrane, CINAHL, and PsycInfo, was conducted. The review included patients diagnosed with chorea and NKX2-1-RD genetic diagnosis, drug therapy as intervention, no comparator, and outcomes of chorea improvement and adverse events. The methodological quality of the studies was assessed, and the study protocol was registered in PROSPERO.
RESULTS
Of the 1417 studies examined, 28 studies met the selection criteria, consisting of 68 patients. The studies reported 22 different treatments for chorea, including carbidopa/levodopa, tetrabenazine, clonazepam, methylphenidate, carbamazepine, topiramate, trihexyphenidyl, haloperidol, propranolol, risperidone, and valproate. No clinical improvements were observed with carbidopa/levodopa, tetrabenazine, or clonazepam, and various adverse effects were reported. However, most patients treated with methylphenidate experienced improvements in chorea and reported only a few negative effects. The quality of evidence was determined to be low.
CONCLUSIONS
The management of chorea in individuals with NKX2-1-RD presents significant heterogeneity and lack of clarity. While the available evidence suggests that methylphenidate may be effective in improving chorea symptoms, the findings should be interpreted with caution due to the limitations of the studies reviewed. Nonetheless, more rigorous and comprehensive studies are necessary to provide sufficient evidence for clinical recommendations.
Topics: Humans; Chorea; Tetrabenazine; Levodopa; Carbidopa; Clonazepam; Methylphenidate
PubMed: 37694681
DOI: 10.1111/ene.16038 -
PloS One 2023To characterize the drug-related problems (DRPs) in high-risk pregnant women with hypertension and gestational diabetes mellitus according to frequency, type, cause, and... (Observational Study)
Observational Study
OBJECTIVE
To characterize the drug-related problems (DRPs) in high-risk pregnant women with hypertension and gestational diabetes mellitus according to frequency, type, cause, and factors associated with their occurrence in the hospital setting.
METHODOLOGY
This is an observational, longitudinal, prospective study that included 571 hospitalized pregnant women with hypertension and gestational diabetes mellitus using at least one medication. DRPs were classified according to the Classification for Drug-Related Problems (PCNE V9.00). In addition to descriptive statistics, a univariate and multivariate logistic regression model was employed to determine the factors associated with the DRPs.
RESULTS
A total of 873 DRPs were identified. The most frequent DRPs were related to therapeutic ineffectiveness (72.2%) and occurrence of adverse events (27.0%) and the main drugs involved were insulins and methyldopa. These were followed in the first five days of treatment by: the ineffectiveness of insulin (24.6%), associated with underdosage (12.9%) or insufficient frequency of administration (9.5%) and methyldopa associated with the occurrence of adverse reactions (40.2%) in the first 48h. Lower maternal age (OR 0.966, 95% CI 0.938-0.995, p = 0.022), lower gestational age (OR 0.966, 95% CI 0.938-0.996, p = 0.026), report of drug hypersensitivity (OR 2.295, 95% CI 1.220-4.317, p = 0.010), longer treatment time (OR 1.237, 95% CI: 1.147-1.333, p = 0.001) and number of prescribed medications (OR 1.211, 95% CI: 0.240-5.476, p = 0.001) were risk factors for occurrence of DRPs.
CONCLUSION
DRPs are frequent in pregnant women with hypertension and gestational diabetes mellitus, and they are mainly related to therapeutic ineffectiveness and the occurrence of adverse events.
Topics: Pregnancy; Humans; Female; Diabetes, Gestational; Drug-Related Side Effects and Adverse Reactions; Prospective Studies; Methyldopa; Hospitals; Hypertension; Insulin
PubMed: 37027363
DOI: 10.1371/journal.pone.0284053 -
The Biochemical Journal Oct 2020Tryptophan metabolites exhibit aryl hydrocarbon receptor (AhR) agonist activity and recent studies show that the phenylalanine metabolites serotonin and carbidopa, a...
Tryptophan metabolites exhibit aryl hydrocarbon receptor (AhR) agonist activity and recent studies show that the phenylalanine metabolites serotonin and carbidopa, a drug used in treating Parkinson's disease, activated the AhR. In this study, we identified the neuroactive hormone dopamine as an inducer of drug-metabolizing enzymes CYP1A1, CYP1B1, and UGT1A1 in colon and glioblastoma cells and similar results were observed for carbidopa. In contrast, carbidopa but not dopamine exhibited AhR activity in BxPC3 pancreatic cancer cells whereas minimal activity was observed for both compounds in Panc1 pancreatic cancer cells. In contrast with a previous report, the induction responses and cytotoxicity of carbidopa was observed only at high concentrations (100 µM) in BxPC3 cells. Our results show that similar to serotonin and several tryptophan metabolites, dopamine is also an AhR-active compound.
Topics: Caco-2 Cells; Carbidopa; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP1B1; Cytochrome P-450 Enzyme Inducers; Dopamine; Glucuronosyltransferase; Humans; Neoplasms; Receptors, Aryl Hydrocarbon
PubMed: 32905582
DOI: 10.1042/BCJ20200440 -
CNS Drugs Feb 2021Infusion of levodopa-carbidopa intestinal gel (LCIG; also designated carbidopa-levodopa enteral suspension) for 16 hours is a standard treatment for patients with... (Review)
Review
Infusion of levodopa-carbidopa intestinal gel (LCIG; also designated carbidopa-levodopa enteral suspension) for 16 hours is a standard treatment for patients with advanced Parkinson's disease, and clinical observations suggest that 24-hour LCIG infusion may further reduce symptoms. This review provides practical advice on the management of patients transitioning to 24-hour LCIG infusion. We review available clinical data for 24-hour infusion and discuss adjustments to dosing, recommendations for monitoring, and management of patient concerns, based on our clinical experience. Data from multiple studies suggest that LCIG may improve non-motor symptoms. Although few studies have examined 24-hour LCIG infusion, available data indicate that certain patients may benefit from around-the-clock treatment. Studies of 24-hour LCIG infusion are limited by small sample sizes and open-label study designs, which may hamper translation to clinical practice. In our experience, we have found that patients may benefit from 24-hour infusion when reductions in nocturnal symptoms and improvements to quality of sleep are needed. Levodopa-unresponsive freezing of gait or poorly controlled troublesome dyskinesias may also indicate a patient may benefit from 24-hour infusion. Dose adjustments, especially of the nocturnal rate, are typically necessary and, as with 16-hour infusion, patients should be monitored for autonomic dysfunction; overnight wearing off symptoms; weight changes; fluctuations in plasma levels of vitamins B/B, folate, and homocysteine; changes in sleep patterns; or worsening of hallucinations, delusions, and/or nightmares. Available data and our clinical experience suggest that 24-hour LCIG may be warranted among selected patients who have poorly controlled nocturnal fluctuations or early morning "off" symptoms.
Topics: Antiparkinson Agents; Carbidopa; Drug Administration Schedule; Drug Combinations; Drug Monitoring; Gels; Humans; Levodopa; Parkinson Disease; Time Factors
PubMed: 33582982
DOI: 10.1007/s40263-020-00782-w -
Pregnancy Hypertension Aug 2021To evaluate community-based health workers' ability to identify cases of hypertension in pregnancy, safely deliver methyldopa and magnesium sulphate and make referrals...
The ability and safety of community-based health workers to safely initiate lifesaving therapies for pre-eclampsia in Ogun State, Nigeria: An analysis of 260 community treatments with MgSO and/or methyldopa.
OBJECTIVES
To evaluate community-based health workers' ability to identify cases of hypertension in pregnancy, safely deliver methyldopa and magnesium sulphate and make referrals when appropriate.
STUDY DESIGN
This was part of Nigeria Community-Level Interventions for Pre-eclampsia (CLIP) cluster randomized controlled trial (NCT01911494). Community-based Health Workers (CHW) recruited pregnant women from five Local Government Areas (clusters) and used mobile health aid for clinical assessment of pre-eclampsia.
MAIN OUTCOME MEASURES
The primary outcome was the number of adverse events that occurred after the administration of magnesium sulphate and/or methyldopa to pregnant women by CHWs.
FINDINGS
Of 8790 women receiving mobile health-guided care, community-based health workers in Nigeria provided 309 women with hypertension (4.2% of delivered women), and safely administered 142 doses of intramuscular magnesium sulphate. Community Heath Extension Workers (CHEWs) and nurses gave fifty-two and sixty-seven doses of intramuscular magnesium sulphate respectively, twenty-three doses were given by other health care workers (midwives, community health officers, health assistants). The high rate of administration by nurses can be explained by turf protection as well as their seniority within the health system. Also, CHEWs and nurses gave 124 doses of oral methyldopa and 126 urgent referrals were completed. There were no complications related to administration of treatment or referral.
INTERPRETATION
These findings demonstrate the ability of community-based health workers to safely administer methyldopa and intramuscular magnesium sulphate. The use of task-sharing, therefore, could drastically reduce the three delays (triage, transport and treatment) associated with high maternal mortality and morbidity in rural communities in low- and middle-income countries.
Topics: Adolescent; Adult; Antihypertensive Agents; Benchmarking; Clinical Competence; Community Health Services; Female; Humans; Magnesium Sulfate; Methyldopa; Middle Aged; Nigeria; Pre-Eclampsia; Pregnancy; Young Adult
PubMed: 34175582
DOI: 10.1016/j.preghy.2021.05.005 -
Advances in Therapy Sep 2019In 2015, the US Food and Drug Administration approved levodopa-carbidopa intestinal gel (LCIG; also known as carbidopa-levodopa enteral suspension in the US) for the... (Review)
Review
In 2015, the US Food and Drug Administration approved levodopa-carbidopa intestinal gel (LCIG; also known as carbidopa-levodopa enteral suspension in the US) for the treatment of motor fluctuations in patients with advanced Parkinson's disease. LCIG provides a continuous infusion of levodopa and carbidopa by means of a portable pump and percutaneous endoscopic gastrojejunostomy tube. The delivery system has a two-fold pharmacokinetic advantage over orally administered carbidopa/levodopa. First, levodopa is delivered in a continuous rather than intermittent, pulsatile fashion. Second, delivery to levodopa's site of absorption in the jejunum bypasses the stomach, thereby avoiding issues with erratic gastric emptying. In blinded prospective clinical trials and observational studies, LCIG has been shown to significantly decrease "off" time, increase "on" time without troublesome dyskinesia, and reduce dyskinesia. Consistent with procedures in previous studies, LCIG initiation and titration in the pivotal US clinical trial were performed in the inpatient setting and followed a standardized protocol. In clinical practice, however, initiation and titration of LCIG have a great degree of flexibility and, in the US, almost always take place in the outpatient setting. Nonetheless, there remains a significant amount of clinician uncertainty regarding titration in outpatient clinical practice. This review aims to shed light on and provide guidance as to the current methods of titration in the outpatient setting, as informed by the medical literature and the authors' experiences. FUNDING: AbbVie, Inc. Plain language summary available for this article.
Topics: Aged; Antiparkinson Agents; Carbidopa; Drug Combinations; Female; Gels; Humans; Infusions, Parenteral; Levodopa; Male; Middle Aged; Observational Studies as Topic; Parkinson Disease; Precision Medicine; Prospective Studies; United States
PubMed: 31278691
DOI: 10.1007/s12325-019-01014-4 -
PloS One 2022To compare maternal and infant outcomes with different antihypertensive medications in pregnancy.
OBJECTIVE
To compare maternal and infant outcomes with different antihypertensive medications in pregnancy.
DESIGN
Retrospective cohort study.
SETTING
Kaiser Permanente, a large healthcare system in the United States.
POPULATION
Women aged 15-49 years with a singleton birth from 2005-2014 treated for hypertension.
METHODS
We identified medication exposure from automated pharmacy data based on the earliest dispensing after the first prenatal visit. Using logistic regression, we calculated weighted outcome prevalences, adjusted odds ratios (aORs) and 95% confidence intervals, with inverse probability of treatment weighting to address confounding.
MAIN OUTCOME MEASURES
Small for gestational age, preterm delivery, neonatal and maternal intensive care unit (ICU) admission, preeclampsia, and stillbirth or termination at > 20 weeks.
RESULTS
Among 6346 deliveries, 87% with chronic hypertension, the risk of the infant being small for gestational age (birthweight < 10th percentile) was lower with methyldopa than labetalol (prevalence 13.6% vs. 16.6%; aOR 0.77, 95% CI 0.63 to 0.92). For birthweight < 3rd percentile the aOR was 0.57 (0.39 to 0.80). Compared with labetalol (26.0%), risk of preterm delivery was similar for methyldopa (26.5%; aOR 1.10 [0.95 to 1.27]) and slightly higher for nifedipine (28.5%; aOR 1.25 [1.06 to 1.46]) and other β-blockers (31.2%; aOR 1.58 [1.07 to 2.23]). Neonatal ICU admission was more common with nifedipine than labetalol (25.9% vs. 23.3%, aOR 1.21 [1.02 to 1.43]) but not elevated with methyldopa. Risks of other outcomes did not differ by medication.
CONCLUSIONS
Risk of most outcomes was similar comparing labetalol, methyldopa and nifedipine. Risk of the infant being small for gestational age was substantially lower for methyldopa, suggesting this medication may warrant further consideration.
Topics: Antihypertensive Agents; Birth Weight; Female; Humans; Hypertension, Pregnancy-Induced; Infant; Infant, Newborn; Infant, Newborn, Diseases; Labetalol; Methyldopa; Nifedipine; Pregnancy; Pregnancy Outcome; Premature Birth; Retrospective Studies
PubMed: 35576217
DOI: 10.1371/journal.pone.0268284 -
The British Journal of Ophthalmology Nov 2018Amblyopia therapy options have traditionally been limited to penalisation of the non-amblyopic eye with either patching or pharmaceutical penalisation. Solid evidence,... (Review)
Review
Amblyopia therapy options have traditionally been limited to penalisation of the non-amblyopic eye with either patching or pharmaceutical penalisation. Solid evidence, mostly from the Pediatric Eye Disease Investigator Group, has validated both number of hours a day of patching and days per week of atropine use. The use of glasses alone has also been established as a good first-line therapy for both anisometropic and strabismic amblyopia. Unfortunately, visual acuity equalisation or even improvement is not always attainable with these methods. Additionally, non-compliance with prescribed therapies contributes to treatment failures, with data supporting difficulty adhering to full treatment sessions. Interest in alternative therapies for amblyopia treatment has long been a topic of interest among researchers and clinicians alike. Incorporating new technology with an understanding of the biological basis of amblyopia has led to enthusiasm for binocular treatment of amblyopia. Early work on perceptual learning as well as more recent enthusiasm for iPad-based dichoptic training have each generated interesting and promising data for vision improvement in amblyopes. Use of pharmaceutical augmentation of traditional therapies has also been investigated. Several different drugs with unique mechanisms of action are thought to be able to neurosensitise the brain and enhance responsiveness to amblyopia therapy. No new treatment has emerged from currently available evidence as superior to the traditional therapies in common practice today. But ongoing investigation into the use of both new technology and the understanding of the neural basis of amblyopia promises alternate or perhaps better cures in the future.
Topics: Amblyopia; Carbidopa; Child; Cytidine Diphosphate Choline; Dopamine Agonists; Drug Combinations; Eyeglasses; Humans; Levodopa; Nootropic Agents; Sensory Deprivation; Vision, Binocular
PubMed: 29777043
DOI: 10.1136/bjophthalmol-2018-312172 -
Journal of Parkinson's Disease 2023Levodopa-carbidopa intestinal gel (LCIG) improves motor and non-motor symptoms in patients with advanced Parkinson's disease (aPD). (Observational Study)
Observational Study
BACKGROUND
Levodopa-carbidopa intestinal gel (LCIG) improves motor and non-motor symptoms in patients with advanced Parkinson's disease (aPD).
OBJECTIVE
To present the final 36-month efficacy and safety results from DUOGLOBE (DUOdopa/Duopa in Patients with Advanced Parkinson's Disease - a GLobal OBservational Study Evaluating Long-Term Effectiveness; NCT02611713).
METHODS
DUOGLOBE was an international, prospective, long-term, real-world, observational study of patients with aPD initiating LCIG in routine clinical care. The primary endpoint was change in patient-reported "Off" time to Month 36. Safety was assessed by monitoring serious adverse events (SAEs).
RESULTS
Significant improvements in "Off" time were maintained over 3 years (mean [SD]: -3.3 hours [3.7]; p < 0.001). There were significant improvements to Month 36 in total scores of the Unified Dyskinesia Rating Scale (-5.9 [23.7]; p = 0.044), Non-Motor Symptoms Scale (-14.3 [40.5]; p = 0.002), Parkinson's Disease Sleep Scale-2 (-5.8 [12.9]; p < 0.001), and Epworth Sleepiness Scale (-1.8 [6.0]; p = 0.008). Health-related quality of life and caregiver burden significantly improved through Months 24 and 30, respectively (Month 24, 8-item Parkinson's Disease Questionnaire Summary Index, -6.0 [22.5]; p = 0.006; Month 30, Modified Caregiver Strain Index, -2.3 [7.6]; p = 0.026). Safety was consistent with the well-established LCIG profile (SAEs: 54.9% of patients; discontinuations: 54.4%; discontinuations due to an adverse event: 27.2%). Of 106 study discontinuations, 32 patients (30.2%) continued LCIG outside the study.
CONCLUSION
DUOGLOBE demonstrates real-world, long-term, reductions in motor and non-motor symptoms in patients with aPD treated with LCIG.
Topics: Humans; Levodopa; Carbidopa; Parkinson Disease; Antiparkinson Agents; Prospective Studies; Quality of Life; Drug Combinations; Gels
PubMed: 37302039
DOI: 10.3233/JPD-225105