Minocycline Mitigation of Tremor Syndrome and Defect of Cognitive and Balance Induced by Harmaline.

INTRODUCTION: Minocycline has anti-inflammatory, anti-apoptotic, and anti-oxidant effects. Preclinical data suggest that minocycline could be beneficial for treating common neurological disorders, including Parkinson disease and multiple sclerosis. METHODS: In this study, the effects of minocycline on harmaline-induced motor and cognitive impairments were studied in male Wistar rats. The rats were divided into four groups of ten animals each. Harmaline was used for the induction of Essential Tremor (ET). Minocycline (90 mg/kg, IP) was administered 30 minutes before the saline or harmaline. Tremor intensity, spontaneous locomotor activity, passive avoidance memory, anxiety-related behaviors, and motor function were assessed in the rats. RESULTS: The results showed that minocycline could recover tremor intensity and step width but failed to recuperate the motor balance. The memory impairments observed in harmaline-treated rats were somewhat reversed by administration of minocycline. The cerebellum and inferior olive nucleus were studied for neuronal degeneration using histochemistry and transmission electron microscopy techniques. Harmaline caused ultrastructural changes and neuronal cell loss in inferior olive and cerebellar Purkinje cells. Minocycline exhibited neuroprotective changes on cerebellar Purkinje cells and inferior olivary neurons. CONCLUSION: These results open new therapeutic perspectives for motor and memory impairments in ET. However, further studies are needed to clarify the exact mechanisms.

Looking into a Deluded Brain through a Neuroimaging Lens.

Delusions are irrational, tenacious, and incorrigible false beliefs that are the most common symptom of a range of brain disorders including schizophrenia, Alzheimer's, and Parkinson's disease. In the case of schizophrenia and other primary delusional disorders, their appearance is often how the disorder is first detected and can be sufficient for diagnosis. At this time, not much is known about the brain dysfunctions leading to delusions, and hindering our understanding is that the complexity of the nature of delusions, and their very unique relevance to the human experience has hampered elucidation of their underlying neurobiology using either patients or animal models. Advances in neuroimaging along with improved psychiatric and cognitive modeling offers us a new opportunity to look with more investigative power into the deluded brain. In this article, based on data obtained from neuroimaging studies, we have attempted to draw a picture of the neural networks involved when delusion is present and evaluate whether different manifestations of delusions engage different regions of the brain.

Relationship between the serum levels of Vitamin D and inflammatory markers in ESRD patients.

BACKGROUND AND AIM: In patients with End-stage renal disease (ESRD), 25-(OH)-Vitamin D3 deficiency is a common problem and also the inflammatory responses increase in these patients. The present study aims to evaluate the relation of 25-(OH)-Vitamin D3 with the indirect inflammatory markers in patients on hemodialysis (HD) and peritoneal dialysis (PD). METHODS: This study was done by cross-sectional method on 85 ESRD patients receiving renal replacement therapy (RRT), from one geographical area. 64 patients on HD and 21 patients on PD who were matched for age and sex were studied. Serum level of 25-(OH) Vitamin D3 was measured in each patient. ESR, CRP and the other routine blood tests were measured as well. RESULTS: The level of 25-OH Vitamin D3 was significantly lower in PD group in comparison to HD group (P: 0/0012, 2/70±0/10 vs 2/05±0/14). Platelet (195/40 ± 7/6 vs 265/52 ± 15/6, P: 0/001) and ESR (46/80 ± 6/89 vs 23/53 ± 1/96, P: 0/003) were significantly higher in PD group. Considering total population of the study (PD and HD), there was a significant association between ESR and serum level of 25-(OH)-Vitamin D3 (r: 0.26, P: 0.036) but no correlation was seen between 25-(OH)-Vitamin D3 and hemoglobin (Hb) or duration of dialysis. On the other hand, in patients on HD, multiple regression analysis revealed a significant relationship between duration of dialysis (P: 0.02), Hb (P: 0.01) and ESR (P: 0.001) with 25-(OH)-Vitamin D3 level. Moreover, there was a relationship between vitamin D3 levels and inflammatory markers as well. CONCLUSIONS: The deficiency of 25-(OH)-Vitamin D3 was followed with increase of ESR as an inflammatory marker in patients on HD. Key words: Inflammation; 25-hydroxy vitamin D; Renal replacement; Dialysis.

Bipolar disorder and the endocannabinoid system.

OBJECTIVE: Bipolar disorder (BD) is a debilitating, lifelong neuropsychiatric illness characterised by unsteady mood states which vacillate from (hypo)mania to depression. Despite the availability of pharmaceutical agents which can be effective in ameliorating the acute affective symptoms and prevent episodic relapse, BD is inadequately treated in a subset of patients. The endocannabinoid system (ECS) is known to exert neuromodulatory effects on other neurotransmitter systems critical in governing emotions. Several studies ranging from clinical to molecular, as well as anecdotal evidence, have placed a spotlight on the potential role of the ECS in the pathophysiology of BD. In this perspective, we present advantages and disadvantages of cannabis use in the management of illness course of BD and provide mechanistic insights into how this system might contribute to the pathophysiology of BD. RESULTS: We highlight the putative role of selective cannabinoid receptor 2 (CB2) agonists in BD and briefly discuss findings which provide a rationale for targeting the ECS to assuage the symptoms of BD. Further, data encourage basic and clinical studies to determine how cannabis and cannabinoids (CBs) can affect mood and to investigate emerging CB-based options as probable treatment approaches. CONCLUSION: The probable role of the ECS has been almost neglected in BD; however, from data available which suggest a role of ECS in mood control, it is justified to support conducting comprehensive studies to determine whether ECS manipulation could positively affect BD. Based on the limited available data, we suggest that activation of CB2 may stabilise mood in this disorder.

Opioids and Cardiac Arrhythmia: A Literature Review.

OBJECTIVE: One of the most important side effects of opioids is their influence on the electrical activity of the heart. This review focusses on the effects of opioids on QT interval prolongation and their arrhythmogenic liability. METHODS: By using various keywords, papers published up to 2018 in different databases were searched and identified. The search terms were opioids names, corrected QT interval, human-ether-a-go-go gene, torsades de pointes (TdP), cardiac arrhythmias, opioid dependence and other relevant terms. It emphasized the effects of each opioid agent alone on electrocardiogram (ECG) and some interactions. RESULTS: Available data indicate that some opioids such as methadone are high-risk even at low doses, and have potential for prolongation of the QT interval and development of TdP, a dangerous ventricular tachycardia. A number of opioids such as tramadol and oxycodone are intermediate risk drugs and may develop long QT interval and TdP in high doses. Some other opioids such as morphine and buprenorphine are low-risk drugs and do not produce QT interval prolongation and TdP at least in routine doses. Opium-consumers are at higher risk of supra-ventricular arrhythmias, sinus bradycardia, cardiac block and atrial fibrillation. CONCLUSION: The cardiac arrhythmogenicity of various opioids is different. Methadone has a higher capability to induce long QT interval and dangerous arrhythmias in conventional doses than others. To reduce of arrhythmogenic risk, high doses of opioids must be used cautiously with periodic monitoring of ECG in high-risk consumers such as patients under opioid maintenance treatment.

Posttraumatic Growth and Its Dimensions in the Mothers of Children with Cancer.

BACKGROUND: Posttraumatic growth resulting from a stressful factor such as the diagnosis and treatment of cancer can positively affect various aspects of a mother's life as the child's main caregiver. The present study aims to determine the level of posttraumatic growth in the mothers of the children with cancer. METHODS: In the present descriptive study, the statistical population consisted of the mothers of the children with cancer referring to oncology clinics or hospitalized in the oncology departments of selected hospitals from June 2016 to October 2016. The samples included 180 eligible mothers selected by convenient sampling. The data were collected using "Posttraumatic Growth Inventory" (PTGI) that determines the psychological growth following exposure to traumatic events with 21 items in 5 domains of new possibilities, relationship with others, appreciation of life, personal strength, and spiritual changes and scored by 6-point Likert scale, ranging from 0 to 105; the higher scores indicate greater growth. The data were analyzed in SPSS-20 using descriptive and inferential statistical tests. RESULTS: The mean age of the participating mothers was 34±5.3, 83.3% of whom were housewives. The majority of the children suffered from leukemia, and cancer onset age was between 3 and 6 in 33.9% of the children. The mothers' mean score of posttraumatic growth was 62.4±18.9, and the highest percentage of scores in various dimensions belonged to "spiritual change" (3.59), "appreciation of life" (3.04), and "relating to others" (3.02). CONCLUSION: Results showed that the experience of having a child with cancer can lead to posttraumatic growth in mothers.

A Brain on a Roller Coaster: Can the Dopamine Reward System Act as a Protagonist to Subdue the Ups and Downs of Bipolar Disorder?

One of the most interesting but tenebrous parts of the bipolar disorder (BD) story is the switch between (hypo)mania and depression, which can give bipolar patients a thrilling, but somewhat perilous, 'ride'. Numerous studies have pointed out that there are some recognizable differences (either state-dependent or state-independent) in several brain regions of people with BD, including components of the brain's reward system. Understanding the underpinning mechanisms of high and low mood statuses in BD has potential, not only for the development of highly specific and selective pharmaceutical agents, but also for better treatment approaches and psychological interventions to manage BD and, thus, give patients a safer ride. Herein, we review evidence that supports involvement of the reward system in the pathophysiology of mood swings, with the main focus on the mesocorticolimbic dopaminergic neural circuitry. Principally using findings from neuroimaging studies, we aim to signpost readers as to how mood alterations may affect different areas of the reward system and how antipsychotic drugs can influence the activity of these brain areas. Finally, we critically evaluate the hypothesis that the mesocorticolimbic dopamine reward system may act as a functional rheostat for different mood states.

Cannabinoids and Tremor Induced by Motor-related Disorders: Friend or Foe?

Tremor arises from an involuntary, rhythmic muscle contraction/relaxation cycle and is a common disabling symptom of many motor-related diseases such as Parkinson disease, multiple sclerosis, Huntington disease, and forms of ataxia. In the wake of anecdotal, largely uncontrolled, observations claiming the amelioration of some symptoms among cannabis smokers, and the high density of cannabinoid receptors in the areas responsible for motor function, including basal ganglia and cerebellum, many researchers have pursued the question of whether cannabinoid-based compounds could be used therapeutically to alleviate tremor associated with central nervous system diseases. In this review, we focus on possible effects of cannabinoid-based medicines, in particular on Parkinsonian and multiple sclerosis-related tremors and the common probable molecular mechanisms. While, at present, inconclusive results have been obtained, future investigations should extend preclinical studies with different cannabinoids to controlled clinical trials to determine potential benefits in tremor.