Following the program of researching metabolic changes in methamphetamine abuser patients, I decided to measure the prevalence of hypocalcaemia in my patients, for three reasons: both hypocalcaemia and methamphetamine abuse can cause seizure(1&3) and both of them, can cause depression.(2&3) and both of them can cause muscle cramp.(2&3) Method We visited all the patients that refereed to (Afarinesh addiction clinic in Karaj, Iran) and asked them if they had taken any calcium pills during their methamphetamine abusing period or not. If the answer was negative, we measured their serum calcium level. Results 15 of the volunteers were suitable for this study. All of them were men and their aged varied between 29 to 47 years old. The average ages was 32.4 years old .In one patient out of 15 that I inspected in this study , the serum calcium level was below 8.8mg/dL(4) and in 2 patients the serum calcium level was upper than 10.5 mg/dL(between 10.5mg/dL and 12mg/dL) (5). This study shows that 6.6 percent of the patients with methamphetamine abuse suffer from hypocalcaemia and 13.3 patients have hyperkalemia.
Ghrelin, an endogenous ligand for growth hormone secretagogue receptor (GHS-R, a G-protein-coupled receptor), is a 28-amino-acid peptide that regulates growth hormone secretion, food intake, reward-seeking behavior and memory performance. In the substantia nigra pars compacta (SNc), ghrelin electrically activates dopaminergic neurons, and increases dopamine concentration in the striatum. However, how ghrelin enhances neuronal excitability remains largely unknown. In the present study, we focus on A-type potassium channels (IA), which has a wide expression on dopaminergic neurons and plays a key role in pacemaker control. Brain slices of the SNc were prepared from C57BL/6 mice of postnatal 15-20 days. The effects of ghrelin on spontaneous firing and IA current of dopaminergic neurons were observed by whole cell patch clamp technique. IA specific blocker 4-AP (1 mM) significantly enhanced the spontaneous firing of dopaminergic neurons, whereas further application of ghrelin (100 nM) had no additional effect on neuronal firing. The application of ghrelin reversibly and significantly decreased the amplitude of IA to 54% of control. Application of H89 (1 μM, PKA selective blocker) did not alter the IA current or the response to ghrelin. However, GF109203X (5 μM, PKC inhibitor) abolished ghrelin-induced inhibition of IA. To assess the involvement of the possible PKC specific subspecies, we then used Gö6976 (20 nM, conventional PKCs selective inhibitor) and Rottlerin (10 μM, PKCδ selective inhibitor). Our results showed that bath application of Gö6976 or Rottlerin alone had no effect on the IA currents, whereas Rottlerin totally abolished the IA current response to ghrelin. Therefore, our findings indicate that inhibition of IA may contribute to the ghrelin-induced excitation of dopaminergic neurons. Ghrelin reduces IA by activation of PKCδ pathway.
Limin Shi has completed her PhD at the age of 29 years from Qingdao University. She is an associated Professor of the department of physiology and pathophysiology in Qingdao University. She has published more than 10 papers in reputed journals.
Lactoferrin (Lf), and the lactoferrin receptor (LfR), regulate cell membrane iron transport, are synthesized in the brain by activated microglia, and their expression is increased in dopaminergic neurons in Parkinson’s disease (PD). We examined the effect of daily intragastric doses of apo-Lf and holo-Lf for 7 days in an experimental 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD and hypothesized that Lf protects against PD through altered iron metabolism. Apo-Lf and holo-Lf antagonized MPTP-induced symptoms including shortening pole climbing time, reducing weight loss, preventing tyrosine hydroxylase immunoreactive (TH-ir) neuron loss in the substantianigra (SN), and restoring dopamine in the striatum. Lf increased SOD1 and Bcl-2 expression, and decreased cleaved caspase-3 expression in the SN. Lf treatment down-regulated iron import protein divalent metal transporter (DMT1) and up-regulated iron export protein ferroportin1 (FPN1) normalizing MPTP-induced accumulation of nigral iron. Lf alleviated MPTP-induced increases in serum iron and ferritin, and decreased serum TIBC, spleen weight, and spleen iron content. Liver iron routine blood test remained unchanged. Our studies showed that Apo-Lf and holo-Lf have a protective effect against MPTP-induced PD, with apo-Lf showing greater efficacy. Therefore, Lf is a new potential treatmentfor PD. More importantly, we put forward a hypothesis that spleen weight loss and lower spleen iron levels might be the original source of iron overload in SN.
Jun Wang has completed her PhD from Qingdao University and postdoctoral studies from University at Buffalo. She is a Professor of the department of physiology and pathophysiology in Qingdao University. She has published more than 30 papers in reputed journals.
Alpha-synuclein plays a central role in synucleinopathies pathogenesis such as Parkinson’s disease (PD). Phosphorylation is the most common and important protein modification linked to α-synuclein pathologies. There is mounting evidence suggested iron and α-synuclein are closely related in PD. In the present study, we aimed to investigate whether and how phosphorylation was involved in iron induced α-synuclein regulations. The results showed that iron could induce pS129 (phosphorylation at Ser129) and α-synuclein upregulation in the substantia nigra of iron overloaded rats and iron treated SH-SY5Y cells, accompanied by the elevated levels of polo-like kinase 2 (PLK2) and casein kinase 2 (CK2). Over-expression of CK2 or PLK2 induced pS129 up-regulation and inhibitors of CK2 or PLK2 could suppress iron induced α-synuclein phosphorylation. Antioxidant NAC could fully block iron induced upregulation of CK2, PLK2 and pS129 levels, indicating oxidative stress plays a critical role in iron induced α-synuclein phosphorylation. However, iron induced α-synuclein up-regulation could only be partially blocked by CK2/PLK2 inhibitor or NAC; enhanced autophagy and proteasome activities seemed to act as compensatory responses to promote intracellular clearance of α-synuclein induced by iron. These findings demonstrate that iron induced oxidative stress is largely responsible for regulating α-synuclein phosphorylation and upregulation via CK2 and PLK2, and α-synuclein upregulation is not fully phosphorylation-dependent.
Junxia Xie has completed her PhD from Ocean University of China and postdoctoral studies from Institute of Physiology, Department of Neurology, University of Munich and Klinikum Groβhardern, München. She is the director of Institute of Brain Science and Disease in Qingdao University. She has published more than 100 papers in reputed journals and has been serving as an editorial board member of repute.
18 volunteers who had referred to our addiction clinic for their methamphetamine abuse problem, were suitable for Measuring their Serum TG Level. Their age varied between 22 and 45 years, with the average being 30.95 years. One patient was female. We first asked them if they have any history of hyperlipidemia before using methamphetamine. The ones with their answers being negative or “unsure” were allowed in the program. 17 volunteers were suitable for measuring their Serum Cholesterol Level. Their age varied between 25 and 45 years, with 33.17 years old being the average. One volunteer was a female. The condition to get in the program program, was the same as the one for the TG test. Results In 4 out of 18 patients, the Serum Triglyceride Level was equal or under 60mg/dL. On the other hand, 22.22 percent of them had a Serum TG Level of under or equal to 60mg/L. In 5 out of 18 patients, the Serum TG Level was higher than 150mgdL. The Serum TG Level varied between 45 to 496 with 166.11 being the average. In 6 out of 17 patients, the Serum Cholesterol Level was higher than 200mg/dL. On the other hand, 35.29 percent of the patients had hypercholesterolemia. In 7 out of 17 patients, the serum cholestrol level was lower than 160mg/dL3. On the other hand, 41.17 percent of the patients had hypocholestrolemia. The Serum Cholesterol Level varied between 94 to 245 mg/dL and the average was 187mg/dL.