Nermin Yucel

Ultra-structural changes and apoptotic activity in cerebellum of post-menopausal-diabetic rats: a histochemical and ultra-structural study

Abstract Diabetes mellitus (DM) is one of the most common and chronic diseases, especially in post-menopausal periods. Neuro-degeneration occurs more frequently in post-menopausal diabetics. Therefore, we investigated ovariectomized rats cerebellar cortex response to the estradiol deficiency and hyperglycemia. For the ovariectomy, the rats were bilaterally ovariectomized, and then DM induced by a single dose of Alloxan monohydrate injection in ovariectomy or/and diabetic groups. During light and electron microscopic examination, degenerated Purkinje cells membrane, swollen organelles, degenerated mitochondria, edema formation and vacuolization were seen in the ovariectomy and ovariectomy-diabetic groups sections. In addition, increased apoptotic activity was observed in the ovariectomy and ovariectomy-diabetic groups compared to the control group. We demonstrated that estradiol and insulin deficiency can affect the cerebellar cortex, which support the hypothesis that the execution of neuronal damages in post-menopausal diabetics. Also, diabetes and menopause are major risks factors for many disorders including nervous system and the number of post-menopausal-diabetics are increasing world-wide.

Effect of agomelatine on adult hippocampus apoptosis and neurogenesis using the stress model of rats.

Agomelatine (AG) is an agonist of melatonin receptors and an antagonist of the 5-HT2C-receptor subtype. The chronobiotic properties of AG are of significant interest due to the disorganization of internal rhythms, which might play a role in the pathophysiology of depression. The present study was designed to assess the effects of the antidepressant-like activity of AG, a new antidepressant drug, on adult neurogenesis and apoptosis using stress-exposed rat brains. Over the period of 1 week, the rats were exposed to light stress twice a day for 1h. After a period of 1 week, the rats were given AG treatment at a dose of either 10mg/kg or 40mg/kg for 15 days. The animals were then scarified, and the obtained tissue sections were stained with immuno-histochemical anti-BrdU, Caspase-3, and Bcl-2 antibodies. Serum brain-derived neurotrophic factor (BDNF) concentrations were measured biochemically using a BDNF Elisa kit. Biochemical BDNF analysis revealed a high concentration of BDNF in the serum of the stress-exposed group, but the concentrations of BDNF were much lower those of the AG-treated groups. Immuno-histochemical analysis revealed that AG treatment decreased the BrdU-positive and Bcl-2-positive cell densities and increased the Caspase-3-positive cell density in the hippocampus of stress-induced rats as compared to those of the stress group. The results of the study demonstrated that AG treatment ameliorated the hippocampal apoptotic cells and increased hippocampal neurogenesis. These results also strengthen the possible relationship between depression and adult neurogenesis, which must be studied further.

Dose-Dependent Paliperidone Associated With Angioedema.

resolution of symptoms suggesting an acute dystonic reaction as the diagnosis. Early recognition of this adverse effect and prompt administration of an anticholinergic in all the cases averted invasive ventilation and more importantly fatal asphyxiation. There is no evidence to suggest that benzodiazepines are necessary for treatment. In fact, these may compromise valuable respiratory reserve. That this reaction develops rarely and with exposure to a disparate variety of dosages of therapy suggest that certain patients may have an underlying predisposition to develop this adverse effect. Other diagnoses that may mimic ALD include anaphylaxis, tardive laryngeal dystonia, neuroleptic malignant syndrome, and respiratory dyskinesia. With particular relevance to our case, we would like to point out that tardive laryngeal dystonia and respiratory dyskinesia are phenomena that develop after prolonged exposure to the drug. They are often seen to coexist with tardive dyskinesia in other parts of the body and do not usually respond to anticholinergics. In our case, the patient had a history of extrapyramidal adverse effects with haloperidol, and unmasking of tardive dystonia from withdrawal of clozapine was also a possibility as this phenomenon has previously been documented in the literature. However, the sudden worsening of dyspnea newly associated with stridor along with rapid improvement after the administration of diphenhydramine all support ALD over tardive dystonia. Furthermore, the absence of fever, hyperthermia, and altered mental status rule out the possibility of neuroleptic malignant syndrome in all the above cases. The most salient diagnosis on the differential for ALD is anaphylaxis. Visualization of adducted vocal cords, absence of edema on laryngoscopy, and prompt response to anticholinergics are all findings suggestive of the former. Nevertheless, it is imperative that physicians maintain a high index of suspicion for ALD in an appropriate clinical scenario, even if administering antihistamines as a first response. Premedication with anticholinergics in the first few weeks of therapy in patients known to experience this reaction has been suggested. Educating physicians about the potential of ALD with SGA use and instructing patients to promptly selfadminister anticholinergic therapy should they notice suggestive symptoms may result in significant reduction of unnecessary invasive ventilation.

Bupropion use: psychotic relapse versus smoking cessation

Bupropion, a first-line pharmacological treatment for nicotine addiction, is a reuptake inhibitor of dopamine and norepinephrine. Dopaminergic effects of bupropion may cause or worsen psychosis (Kumar et al., 2011; Munoli et al., 2014). We reported a case with schizoaffective disorder (SD), who presented with bupropion-induced acute psychotic episode. A 36-year-old man diagnosed to have SD, who has been on remission with risperidone 3 mg/d, Valproic Acid (VA) 1000 mg/d for four years. Family physician prescribed bupropion 300 mg/d two months ago for smoking cessation. The patient reported that the symptoms appeared on the 15th day of bupropion use. During psychiatric examination; he seemed deteriorated and presented logorrhea, elevated mood, disorganized behavior and speech, paranoid-grandiose delusions, ideas of reference, delusions of persecution, auditoryvisual hallucinations and insomnia. No impairment in orientation and memory functions was observed. PANSS score was 132/210. He has been initially treated with a combination of risperidone 3 mg/d and VA 1000 mg/d for three weeks and on the 3rd week, only his psychomotor agitation was alleviated. An increase in the dosage of risperidone to 6 mg/d caused exacerbation in extrapyramidal symptoms and as a result, biperidene 2-4-6 mg/d was added to his treatment. After dosage titration, his psychotic symptoms worsened and he did not respond to treatment. Risperidone was discontinued gradually and clozapine was added to VA. As soon as clozapine dose was titrated up to 250 mg/d, the patient’s symptoms and PANSS (58/210) scores showed significant improvement. Psychosis as a side effect of bupropion is rare in patients without a pre-existing history of psychosis (Javelot et al., 2009, 2010). Appearance of psychotic symptoms after bupropion use may be associated with inhibition of dopamine reuptake (Javelot et al., 2009, 2010; Kumar et al., 2011) especially in patients with history of psychotic symptoms. Treatment of bupropion-induced psychosis may be difficult and achieving remission may take some months. Healthcare professionals should check for any psychotic symptoms or disease before prescribing bupropion for smoking cessation.

Fog cloud in front of the Lewy bodies dementia: delirium -

Lewy body dementia (LBD) is the second most common form of dementia after Alzheimer disease. Clinical symptoms include acute onset of cognitive fluctuations accompanied by dementia, visual hallucinations, disorientation and sleep disorders that suggest initially the diagnosis of delirium. Antipsychotic medication for the treatment of delirium worsens the symptoms due to neuroleptic sensitivity associated with increased morbidity and mortality patients with LBD. In literature, there are rare case reports with overlooked LBD that presented like delirium symptoms. Additionally, it was declared that quetiapine and cholinesterase inhibitors have individually efficacy on treatment of LBD. In this case, we present a woman who had difficulty for diagnosis due to misdiagnosis of LCD and treatment with quetiapine and rivastigmine.