Resistant Chorea Successfully Treated with Intravenous Immunoglobulin: A Case Report

Sydenham’s chorea (SC) is common cause of acquired chorea in childhood. SC occurs mainly in children with untreated streptococcal infections. An effective list of therapeutic options has been used to treat this disorder: antiepileptic drugs (valproic acid, carbamazepine etc.), haloperidol, chlorpromazine, amphetamines, steroids, plasma exchange and intravenous immunoglobulins (IVIG). We report a 12-year-old girl with carditis and severely generalized chorea and successfully treated with IVIG. This case report shows that IVIG is an effective treatment for the chorea cases resistant to anticonvulsants, dopamine antagonists and steroids, although larger studies are needed to confirm this conclusion.

Zebrafish Larvae's Response to Electricity is Mediated by Dopaminergic Agonists and Antagonists

The signaling molecular mechanisms in zebrafish response to electricity are unknown, so here we asked if changes to dopaminergic signaling pathways can affect their electrically-evoked locomotion. To answer this question, the effects of multiple selective and non-selective dopamine compounds on the electric response of zebrafish larvae is investigated. A microfluidic device with enhanced control of experimentation with multiple larvae is used, which features a novel design to immobilize four zebrafish larvae in parallel and expose them to electric current that induces tail locomotion. In 6 days post-fertilization zebrafish larvae, the electric induced locomotor response is quantified in terms of the tail movement duration and beating frequency to discern the effect of non-lethal concentrations of dopaminergic agonists (apomorphine, SKF-81297, and quinpirole), and antagonists (butaclamol, SCH-23390, and haloperidol). All dopamine antagonists decrease locomotor activity, while dopamine agonists do not induce similar behaviours in larvae. The D2- like selective dopamine agonist quinpirole enhances movement. However, exposure to non-selective and D1-selective dopamine agonists apomorphine and SKF-81297 cause no significant change in the electric response. Exposing larvae that were pre-treated with butaclamol and haloperidol to apomorphine and quinpirole, respectively, restores electric locomotion. The results demonstrate a correlation between electric response and the dopamine signalling pathway. We propose that the electrofluidic assay has profound application potential as a chemical screening method when investigating biological pathways, behaviors, and brain disorders.

Analysis of Rod/Cone Gap Junctions from the Reconstruction of Mouse Photoreceptor Terminals

Using serial blockface-scanning electron microscopy (SBF-SEM) and focused ion beam-scanning electron microscopy (FIB-SEM), combined with confocal microscopy for the gap junction protein Cx36, we reconstructed mouse photoreceptor terminals and located the gap junctions between them. An exuberant spray of fine telodendria extends from each cone pedicle (including blue cones) to contact 40-50 nearby rod spherules where Cx36 clusters were located, close to the mouth of the synaptic opening. There were approximately Cx36 clusters per cone 50 pedicle and 2-3 per rod spherule. We were unable to detect rod/rod or cone/cone coupling. Thus, rod/cone coupling accounts for nearly all gap junctions between photoreceptors. Our calculations suggest a mean of 82 Cx36 channels between a rod/cone pair of which 25% are open at rest. Rod/cone gap junctions are modulated by dopamine. Comparing our morphological calculations of maximum coupling to previous physiological results suggests that dopamine antagonists can drive rod/cone gap junctions to a surprisingly high open probability, approaching 100%.

Effects of prokinetics on the digestive tract.

Background: Functional gastrointestinal disorders account for at least a third of visits to gastroenterology clinics. Despite pathophysiological complexity, an impaired gut motility may be frequently present in these disorders. Introduction: Prokinetics are a class of drugs that promote gastrointestinal motility, acelerate transit and potentially improve digestive symptoms. Several prokinetic agents with a great variety of mechanisms of action are available.The purpose of this paper is to update our current knowledge about efficacy and safety of prokinetics. Methods: A literature search for efficacy and safety of prokinetics was carried out using the online databases of Pubmed, Medline and Cochrane. Results : On the basis of different receptorial action, prokinetics mainly comprise dopamine antagonists, 5HT4 agonists, motilin agonists, ghrelin agonists and cholinergic agonists. Prokinetics have the potential to improve motility function in all segments of digestive tract, from the esophagus to colon. In particular, drug international agencies approved antidopaminergic metoclopramide for the treatment of gastroparesis and serotoninergic prucalopride for chronic constipation not responsive to traditional laxatyves. Arrythmias by QT prolongation and galactorrea by prolactin stimulation are the more frequent side effects related to prokinetics use. Conclusions: Old and new prokinetics are effective in ameliorating digestive motility disorders and related symptoms and consequently are widely prescribed. Special attention should be paid to potential adverse events of these agents.

IN VITRO ANTIOXIDANT AND ANTI-DOPAMINERGIC ACTIVITY OF ALKALOID-RICH FRACTION ISOLATED FRO MLEAVES OF MURRAYA KOENIGII

Anti-dopaminergic or dopamine antagonists are preferably used as anti-psychotics, in schizophrenia, bipolar disorders and stimulant psychosis. They are also effective in many other gastrointestinal disorders including nausea and vomiting. Many herbal drugs like digoxin, quinine, morphine, are known for their therapeutic importance. The objective of this study was to use animal models to investigate the impact of Murraya koenigii L. leaves (MK) as an anti-dopaminergic.Pet ether extract of MK (PEMK) and alkaloids isolated from PEMK (AFMK) has shown potent antioxidant activity when tested against invitro antioxidant methods like free radical scavenging by DPPH method, total antioxidant activity by thiocyanate method and H2O2scavenging activity. Significant decreasein the dopaminergic activity was observed in validated animal models like haloperidol-induced catalepsy in mice, apomorphine-induced stereotypic behavior, foot shock-induced aggression and phenobarbitone-induced sleeping behavior. This may be attributed to the presence of carbazole alkaloids having antioxidant potential.

FREQUENCY OF THYROID DYSFUNCTION IN CHRONIC KIDNEY DISEASE PATIENTS

Objectives: To determine the frequency of thyroid dysfunction in chronic kidney disease patients. Methods: It was a Cross-sectional Study at department of Medicine, Bahawal Victoria Hospital, Bahawalpur. Duration of the study was from 20th October 2018 to 19th April 2019. 72 patients with chronic kidney disease, 20 to 60 years of age and of both genders were included. Patients with known thyroid disorders or taking medication that can affect thyroid function (dopamine antagonists, antiepileptic, oral contraceptives, lithium, and glucocorticoids) were excluded. Venous blood sample was taken and sent to the laboratory for thyroid function tests. Results: Age of the patients included in this study was from 20 to 60 year and mean age was 41.97 ± 9.76 years. Most of them 42 (58.33%) were between 41 to 60 years of age. Out of 72 patients, 44 (61.11%) were male and 28 (38.89%) were female with male to female ratio of 1.6:1. Mean duration of disease in our study was 5.71 ± 2.50 years .Mean BMI was 27.75 ± 3.01 kg/m2.Thyroid dysfunction was present in 23 (31.94%) patients of chronic kidney disease. Conclusion: Thyroid dysfunction is frequently found in chronic kidney disease patients.

Very-Low-Dose Levodopa Therapy for Pediatric Neurological Disorders: A Preliminary Questionnaire in Japan

Introduction: Post-synaptic dopamine receptor supersensitivity (DARSS) has been extensively researched by Dr. Masaya Segawa, who has investigated the efficacy of very-low-dose levodopa therapy (VLDT; 0.5–1 mg/kg/day). Considerable Japanese research supports the possibility that VLDT could be used to treat pediatric neurological disorders. We conducted an on-line survey in 2014 to collect real-world data on the use of VLDT to treat DARSS.Methods: A two-step survey, including a screening test and questionnaire, was posted on a private internet site that could be accessed via the VLDT Research Group home page, and 1,165 pediatric neurologists across Japan were invited to complete it.Results: A total of 25 respondents reported prescribing VLDT; 19 used VLDT to treat autism spectrum disorder, 14 for tics, 12 for speech delay, 9 for Rett syndrome, 7 for attention-deficit/hyperactivity disorder, intellectual disability, and 6 for sleep problems. Twelve respondents reported prescribing a dose of 0.5 mg/kg. Twenty-two reported that VLDT was effective for treating behavioral problems, and twenty reported a good efficacy for treating motor symptoms. Adverse events had a low incidence. Notably, respondents chose VLDT for its possible action in DARSS and for its safety. VLDT was commonly used for behavioral problems in patients younger than 5 years, and for motor symptoms in aged 5–9 years.Conclusion: VLDT could safely treat behavioral and motor symptoms in pediatric neurological disorders. In contrast, dopamine antagonists are associated with potent efficacy, but with adverse effects such as sleepiness and obesity. Further surveys should be conducted with a broader participants.

Modern approaches to drug treatment for vestibular vertigo

In recent years, some progress has been achieved in elaborating the algorithms and standards for the treatment of many conditions accompanied by vertigo. The current possibilities of treating vestibular vertigo consist of a gradually expanding arsenal of symptomatic and pathogenetic drugs. Among the drugs used for the symptomatic treatment of vestibular vertigo, there are vestibular suppressants (antihistamines, benzodiazepines, and calcium antagonists) and antiemetics (dopamine antagonists and serotonin 5-HT3 receptor antagonists). The paper discusses the possibilities of using betahistine and vitamin D as pathogenetic agents for recurrent benign paroxysmal positional vertigo; diuretics, betahistine (including the new prolonged release formulation Betaserc® Long), glucocorticoids, and gentamicin for Meniere's disease; triptans, beta-blockers, tricyclic antidepressants, and anticonvulsants for vestibular migraine; glucocorticoids, antiviral agents, and drugs that accelerate vestibular compensation for acute unilateral peripheral vestibulopathy (vestibular neuritis and Ramsey Hunt syndrome).The emergence of new drugs, as well as the design of new dosage forms that enhance patient adherence to the prescribed treatment, can improve quality of life in patients suffering from diseases that have recently led to long-term disability or even incapacitation.