- Methyldopa blocks MHC class II binding to disease-specific antigens in autoimmune diabetes. [Journal Article]
- JCIJ Clin Invest 2018 Feb 13
- Major histocompatibility (MHC) class II molecules are strongly associated with many autoimmune disorders. In type 1 diabetes, the DQ8 molecule is common, confers significant disease risk and is invol...
Major histocompatibility (MHC) class II molecules are strongly associated with many autoimmune disorders. In type 1 diabetes, the DQ8 molecule is common, confers significant disease risk and is involved in disease pathogenesis. We hypothesized blocking DQ8 antigen presentation would provide therapeutic benefit by preventing recognition of self-peptides by pathogenic T cells. We used the crystal structure of DQ8 to select drug-like small molecules predicted to bind structural pockets in the MHC antigen-binding cleft. A limited number of the predicted compounds inhibited DQ8 antigen presentation in vitro with one compound preventing insulin autoantibody production and delaying diabetes onset in an animal model of spontaneous autoimmune diabetes. An existing drug of similar structure, methyldopa, specifically blocked DQ8 in recent-onset patients with type 1 diabetes along with reducing inflammatory T cell responses toward insulin, highlighting the relevance of blocking disease-specific MHC class II antigen presentation to treat autoimmunity.
- Non-antipsychotic catecholaminergic drugs for antipsychotic-induced tardive dyskinesia. [Review]
- CDCochrane Database Syst Rev 2018 01 18; 1:CD000458
- CONCLUSIONS: Although there has been a large amount of research in this area, many studies were excluded due to inherent problems in the nature of their cross-over designs. Usually data are not reported before the cross-over and the nature of TD and its likely response to treatments make it imprudent to use this data. The review provides little usable information for service users or providers and more well-designed and well-reported studies are indicated.
- Clinical Value of 18F-FDOPA PET/CT With Contrast Enhancement and Without Carbidopa Premedication in Patients with Insulinoma. [Journal Article]
- ARAnticancer Res 2018; 38(1):353-358
- CONCLUSIONS: Based on our data, 18F-DOPA PET/CT, with contrast enhancement and without carbidopa premedication, as a 'one-stop' diagnostic modality is a viable option for insulinoma detection.
- Patient Preferences for Device-Aided Treatments Indicated for Advanced Parkinson Disease. [Journal Article]
- VHValue Health 2017; 20(10):1383-1393
- CONCLUSIONS: This study clarifies the patient perspective in therapeutic choices for advanced PD. These findings may help improve communication between patients and providers and also provide evidence on patient preferences to inform regulatory and access decisions.
- Case 38-2017. A 20-Year-Old Woman with Seizures and Progressive Dystonia. [Case Reports]
- NEJMN Engl J Med 2017 Dec 14; 377(24):2376-2385
- Voltammetric Determination of Penicillamine Using a Carbon Paste Electrode Modified with Multiwall Carbon Nanotubes In the Presence of Methyldopa as a Mediator. [Journal Article]
- IJIran J Pharm Res 2017; 16(3):1019-1029
- A multiwall carbon nanotubes-modified carbon paste electrode (MWCNTs/MCPE) was fabricated and used to study the electrooxidation of penicillamine (PA) by electrochemical methods in the presence of me...
A multiwall carbon nanotubes-modified carbon paste electrode (MWCNTs/MCPE) was fabricated and used to study the electrooxidation of penicillamine (PA) by electrochemical methods in the presence of methyldopa (MDOP) as a homogeneous mediator. The electrochemical oxidation of PA on the new sensor has been carefully studied. The kinetic parameters such as electron transfer coefficient, α, and catalytic reaction rate constant, K/h, were also determined using electrochemical approaches. The electrocatalytic oxidation peak current of PA showed a linear dependent on the PA concentrations and linear calibration curves were obtained in the ranges of 0.2-250.0 µM of PA concentration with square wave voltammetry (SWV) method. The detection limit (3σ) was determined as 0.1 µM. This sensor was also examined as a fast, selective, simple and precise new sensor for voltammetric determination of PA in real samples such as drug and urine.
- Adverse drug reactions in high-risk pregnant women: A prospective study. [Journal Article]
- SPSaudi Pharm J 2017; 25(7):1073-1077
- CONCLUSIONS: Overall, ADRs were not common events among high-risk pregnant women and no adverse pregnancy outcomes following these events were observed.
- Carbidopa: a selective Ah receptor modulator (SAhRM). [Journal Article]
- BJBiochem J 2017 Nov 06; 474(22):3763-3765
- The aryl hydrocarbon receptor (AhR) was discovered as the intracellular receptor that bound with high affinity to the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and the AhR is...
The aryl hydrocarbon receptor (AhR) was discovered as the intracellular receptor that bound with high affinity to the environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and the AhR is required for mediating the toxicity induced by TCDD. Subsequent studies show that the AhR binds structurally diverse chemicals including plant-derived compounds that promote health and several AhR-active pharmaceuticals that exhibit anticancer activity. In this issue, there is a report that carbidopa, a drug used for treating Parkinson's disease, is also an AhR ligand, and this compound inhibits pancreatic cancer cell and tumor growth. These results are consistent with activities of other AhR-active compounds that inhibit carcinogenesis. Like carbidopa, these chemicals are selective AhR modulators with potential clinical applications that are AhR-dependent.
- Carbidopa is an activator of aryl hydrocarbon receptor with potential for cancer therapy. [Journal Article]
- BJBiochem J 2017 Sep 28; 474(20):3391-3402
- Carbidopa is used with l-DOPA (l-3,4-dihydroxyphenylalanine) to treat Parkinson's disease (PD). PD patients exhibit lower incidence of most cancers including pancreatic cancer, but with the notable e...
Carbidopa is used with l-DOPA (l-3,4-dihydroxyphenylalanine) to treat Parkinson's disease (PD). PD patients exhibit lower incidence of most cancers including pancreatic cancer, but with the notable exception of melanoma. The decreased cancer incidence is not due to l-DOPA; however, the relevance of Carbidopa to this phenomenon has not been investigated. Here, we tested the hypothesis that Carbidopa, independent of l-DOPA, might elicit an anticancer effect. Carbidopa inhibited pancreatic cancer cell proliferation both in vitro and in vivo Based on structural similarity with phenylhydrazine, an inhibitor of indoleamine-2,3-dioxygenase-1 (IDO1), we predicted that Carbidopa might also inhibit IDO1, thus providing a molecular basis for its anticancer effect. The inhibitory effect was confirmed using human recombinant IDO1. To demonstrate the inhibition in intact cells, AhR (aryl hydrocarbon receptor) activity was monitored as readout for IDO1-mediated generation of the endogenous AhR agonist kynurenine in pancreatic and liver cancer cells. Surprisingly, Carbidopa did not inhibit but instead potentiated AhR signaling, evident from increased CYP1A1 (cytochrome P450 family 1 subfamily A member 1), CYP1A2, and CYP1B1 expression. In pancreatic and liver cancer cells, Carbidopa promoted AhR nuclear localization. AhR antagonists blocked Carbidopa-dependent activation of AhR signaling. The inhibitory effect on pancreatic cancer cells in vitro and in vivo and the activation of AhR occurred at therapeutic concentrations of Carbidopa. Chromatin immunoprecipitation assay further confirmed that Carbidopa promoted AhR binding to its target gene CYP1A1 leading to its induction. We conclude that Carbidopa is an AhR agonist and suppresses pancreatic cancer. Hence, Carbidopa could potentially be re-purposed to treat pancreatic cancer and possibly other cancers as well.
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- Current Trend of Using Anti-Hypertensives in Pregnancy and Postpartum Period in a Tertiary Level Hospital. [Journal Article]
- MMMymensingh Med J 2017; 26(3):525-529
- Hypertensive disorders are one of the most common disorders in pregnancy. They are amongst the major cause of maternal and perinatal morbidity and mortality. Incidence is increasing in developing cou...
Hypertensive disorders are one of the most common disorders in pregnancy. They are amongst the major cause of maternal and perinatal morbidity and mortality. Incidence is increasing in developing countries like Bangladesh. This cross sectional descriptive study has done to observe the utilization of antihypertensive drugs in hypertensive disorders of pregnancy and conducted from January 2016 to December 2016 in the department of Pharmacology in collaboration with department of Gynecology and Obstetrics in Mymensingh Medical College Hospital, Mymensingh, Bangladesh. Non random purposive sampling technique was used. Total of 300 patients participated in the study, 281 anti partum and 19 postpartum. Age distribution showed 42% patients were in 21-25 years age group. Majority of the participants (91%) were housewife and majority (79%) came from poor socioeconomic status with below SSC education (68%). About 82% patients lived in rural area. Trimester and gravida wise distribution showed most of the participants were 3rd trimester (61%) and primigravida (57%) and only 6% patients belong to postpartum period. In this study preeclampsia was highest (63.8%) among all other types of hypertensive diseases in pregnancy. Majority of the patient were preferred for dual therapy (53%), mono therapy was used in 29% of cases. Most frequently given drug in pregnancy associated hypertension was methyldopa that is 88.33% (single 22.3%, combination 66%). Second most commonly used drug was nifidipine consisting of 47.6% but used in combination in all cases. Average number of anti hypertensive drugs prescribed per prescription was 1.87 and majorities (92%) were from essential drug list but used as trade name. Preeclampsia and eclampsia were more common among the hypertensive disorders in tertiary level hospital cases. Methyldopa was found to be the commonest prescribed antihypertensive in monotherapy and in combination.