Assessment of trace elements in serum of acute lymphoblastic and myeloid leukemia patients.

AIM: Trace elements play a key role in human metabolism. The aim of the present study was to measure essential trace elements in the serum of patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). MATERIALS AND METHODS: 32 patients with ALL and 16 patients with AML were studied. The control group consisted of 36 subjects. Serum levels of the trace elements selenium, copper and zinc were measured by spectrophotometry. RESULTS: The mean of copper concentrations in the groups of patients with AML and ALL was significantly higher than in the control group (p < 0.0001), whereas serum levels of selenium and zinc were significantly lower in AML patients (p < 0.0001). Also in ALL patients the levels of selenium and zinc were significantly decreased compared with the control group (p < 0.0001; p = 0.0003). CONCLUSION: Our results indicate that the levels of zinc and selenium are significantly decreased and copper levels are significantly increased in the serum of patients with acute leukemia (AML, ALL).

Brain mitochondrial ATP-insensitive large conductance Ca⁺²-activated K⁺ channel properties are altered in a rat model of amyloid-ß neurotoxicity.

Mitochondrial dysfunction is a hallmark of amyloid-beta (Aß)-induced neuronal toxicity in Alzheimer's disease (AD). However, the underlying mechanism of how Aß affects mitochondrial function remains uncertain. Because mitochondrial potassium channels have been involved in several mitochondrial functions including cytoprotection, apoptosis and calcium homeostasis, a study was undertaken to investigate whether the gating behavior of the mitochondrial ATP- and ChTx-insensitive-IbTx-sensitive Ca(2+)-activated potassium channel (mitoBKCa) is altered in a rat model of Aß neurotoxicity. Aß1-42 (4 µg/µl) was intracerebroventricularly injected in male Wistar rats (220-250 g). Brain Aß accumulation was confirmed two weeks later on the basis of an immunohistochemistry staining assay, and physiological impacts measured in passive avoidance task cognitive performance experiments. Brain mitochondrial inner membranes were then extracted and membrane vesicles prepared for channel incorporation into bilayer lipid. Purity of the cell fraction was confirmed by Western blot using specific markers of mitochondria, plasma membrane, endoplasmic reticulum, and Golgi. Our results first provide evidence for differences in mitoBKCa ion permeation properties with channels coming from Aß vesicle preparations characterized by an inward rectifying I-V curve, in contrast to control mitoBKCa channels which showed a linear I-V relationship under the same ionic conditions (200 mM cis/50mM trans). More importantly the open probability of channels from Aß vesicles appeared 1.5 to 2.5 smaller compared to controls, the most significant decrease being observed at depolarizing potentials (30 mV to 50 mV). Because BKCa-ß4 subunit has been documented to shift the BKCa channel voltage dependence curve, a Western blot analysis was undertaken where expression of mitoBKCa α and ß4 subunits was estimated using anti-α and ß4 subunit antibodies. Our results indicated a significant increase in mitoBKCa-ß4 subunit expression coupled to a decrease in the expression of α subunit. Our results thus demonstrate a modification in the mitoBKCa channel gating properties in membrane preparations coming from a rat model of Aß neurotoxicity, an effect potentially linked to a change in mitoBKCa-ß4 and -α subunits expression or increased ROS production due to an enhanced Aß mitochondrial accumulation. Our results may provide new insights into the cellular mechanisms underlying mitochondrial dysfunctions in Aß neurotoxicity.

Impairment of brain mitochondrial charybdotoxin- and ATP-insensitive BK channel activities in diabetes.

Existing evidence indicates an impairment of mitochondrial functions and alterations in potassium channel activities in diabetes. Because mitochondrial potassium channels have been involved in several mitochondrial functions including cytoprotection, apoptosis and calcium homeostasis, a study was carried out to consider whether the gating behavior of the mitochondrial ATP- and ChTx-insensitive Ca(2+)-activated potassium channel (mitoBKCa) is altered in a streptozotocin (STZ) model of diabetes. Using ion channel incorporation of brain mitochondrial inner membrane into the bilayer lipid membrane, we provide in this work evidence for modifications of the mitoBKCa ion permeation properties with channels from vesicles preparations coming from diabetic rats characterized by a significant decrease in conductance. More importantly, the open probability of channels from diabetic rats was reduced 1.5-2.5 fold compared to control, the most significant decrease being observed at depolarizing potentials. Because BKCa ß4 subunit has been documented to left shift the BKCa channel voltage dependence curve in high Ca(2+) conditions, a Western blot analysis was undertaken where the expression of mitoBKCa α and ß4 subunits was estimated using of anti-α and ß4 subunit antibodies. Our results indicated a significant decrease in mitoBKCa ß4 subunit expression coupled to a decrease in the expression of α subunit, an observation compatible with the observed decrease in Ca(2+) sensitivity. Our results thus demonstrate a modification in the mitoBKCa channel gating properties in membrane preparations coming from STZ model of diabetic rats, an effect potentially linked to a change in mitoBKCa ß4 and α subunits expression and/or to an increase in reactive oxygen species production in high glucose conditions.

Physico-chemical analysis of drinking groundwater of around Tehran by seasonal variation.

This study was a cross-sectional descriptive study and done in four seasons during April 2011 to March 2012.The objective of the present study was to examine Physico-chemical properties of groundwater around Tehran. The results are also compared with the guideline values of Iranian legislation. A total of 160 drinking water samples were collected from different drinking groundwater around the Tehran. Total Dissolved Solids (TDS), conductivity and pH, were measured by using standard methods and the concentration of ions Cl-, F-, NO3-, NO2-, Br-, SO4(2-), PO4(3-), Ca2+, K+, Na+ and NH4+ in groundwater was performed using Ion chromatography (Metrohm Company, USA) with standard method. This study showed that most of the parameters in groundwater were below the Iranian permissible limit except total dissolved solids (N = 2), conductivity (N = 2), nitrate as NO3- (N = 22), chloride (N = 3), sulphate (N = 2), fluoride (N = 3) and ammonia (N = 8). There were significant differences (p < 0.05) between physico-chemical parameters such as pH, nitrite (NO2-), sodium, potassium, sulphate, ammonia, bromide and phosphate in different seasons. These results are important, not only for the many people who drink groundwater but also for the health supervisory agencies such as Ministry of Health and Institute of Standards and Industrial of Iran (ISIRI) to have more effective control on groundwater.

Modulation of the hepatocyte rough endoplasmic reticulum single chloride channel by nucleotide-Mg2+ interaction.

The effect of nucleotides on single chloride channels derived from rat hepatocyte rough endoplasmic reticulum vesicles incorporated into bilayer lipid membrane was investigated. The single chloride channel currents were measured in 200/50 mmol/l KCl cis/trans solutions. Adding 2.5 mM adenosine triphosphate (ATP) and adenosine diphosphate (ADP) did not influence channel activity. However, MgATP addition inhibited the chloride channels by decreasing the channel open probability (Po) and current amplitude, whereas mixture of Mg(2+) and ADP activated the chloride channel by increasing the Po and unitary current amplitude. According to the results, there is a novel regulation mechanism for rough endoplasmic reticulum (RER) Cl(-) channel activity by intracellular MgATP and mixture of Mg(2+) and ADP that would result in significant inhibition by MgATP and activation by mixture of Mg(2+) and ADP. These modulatory effects of nucleotide-Mg(2+) complexes on chloride channels may be dependent on their chemical structure configuration. It seems that Mg-nucleotide-ion channel interactions are involved to produce a regulatory response for RER chloride channels.

Evaluation of serum levels of essential trace elements in patients with pulmonary tuberculosis before and after treatment by age and gender.

The purpose of this study was to evaluate the levels of Zinc, Copper, Iron and Copper/Zinc ratio in the serum of adult patients with pulmonary tuberculosis in Iran. Serum levels of Zinc and Copper were determined by flame atomic absorption spectrophotometer and scrum iron concentration was measured by using an Auto Analyzer. The study group consisted of 50 pulmonary tuberculosis patients before treatment and after 6 months of anti-tubercular therapy. Levels of scrum Zn (p < 0.001) and Fe (p < 0.001) in TB patients were significantly increased after 6 months of anti-tubercular therapy. However, serum Cu concentration (p < 0.01) and Cu/Zn ratio (p < 0.05) were decreased after 6 months of anti-tubercular therapy. Some studies indicated a strong association of Zn, Cu, Fe and the Cu/Zn ratio with TB. In this study, we found remarkable change in Cu/Zn ratio. Some researchers mentioned that serum Cu/Zn ratio could be used as an important laboratory marker for diagnosis and treatment of tuberculosis. They also mentioned that trace element levels must be closely monitored during the process of disease.

How many types of large conductance Ca⁺²-activated potassium channels exist in brain mitochondrial inner membrane: evidence for a new mitochondrial large conductance Ca²âº-activated potassium channel in brain mitochondria.

Recently, we have reported electropharmacological properties of a charybdotoxin (ChTx)- and ATP-insensitive-iberiotoxin (IbTx)-sensitive large conductance Ca⁺²-activated potassium (BKCa) channel in almost purified brain mitochondrial inner membrane vesicles. In this work, we report the single-channel characterization of a new BK channel from rat brain mitochondrial inner membrane (mitochondrial large conductance Ca²âº-activated potassium channel, mitoBKCa channel) incorporated into a planar lipid bilayer. The channel conductance was 565 pS in 200 mM KCl cis/50 mM KCl trans. The channel open probability appeared voltage-independent at -40 to +40 mV. Adding 10 mM 4-aminopyridine (4-AP) at positive and negative potentials and 2.5 mM ATP at positive voltages inhibited the channel activities. Notably, addition of 70 µM glibenclamide to the cis side had no effect on the channel behavior. Hence, it can be concluded that there are, at least, two different types of mitoBKCa channels in brain mitochondrial membrane, and the IbTx-, ChTx-, and ATP-sensitive mitoBKCa channels may be activated during the decline of cell metabolism.

Electro-pharmacological profile of a mitochondrial inner membrane big-potassium channel from rat brain.

Recent studies have indicated a calcium-activated large conductance potassium channel in rat brain mitochondrial inner membrane (mitoBK channel). Accordingly, we have characterized the functional and pharmacological profile of a BK channel from rat brain mitochondria in the present study. Brain mitochondrial inner membrane preparations were subjected to SDS-PAGE analysis and channel protein reconstitution into planar lipid bilayers. Western blotting and antibodies directed against various cellular proteins revealed that mitochondrial inner membrane fractions did not contain specific proteins of the other subcellular compartments except a very small fraction of endoplasmic reticulum. Channel incorporation into planar lipid bilayers revealed a voltage dependent 211 pS potassium channel with a voltage for half activation (V(1/2)) of 11.4±1.1mV and an effective gating charge z(d) of 4.7±0.9. Gating and conducting behaviors of this channel were unaffected by the addition of 2.5mM ATP, and 500 nM charybdotoxin (ChTx), but the channel appeared sensitive to 100 nM iberiotoxin (IbTx). Adding 10mM TEA at positive potentials and 10mM 4-AP at negative or positive voltages inhibited the channel activities. These results demonstrate that the mitoBK channel, present in brain mitochondrial inner membrane, displays different pharmacological properties than those classically described for plasma membrane, especially in regard to its sensitivity to iberiotoxin and charybdotoxin sensitivity.

Evaluation of serum levels of zinc, copper, iron, and zinc/copper ratio in cutaneous leishmaniasis.

BACKGROUND: The purpose of this study was to evaluate the levels of zinc (Zn), copper (Cu), iron (Fe) and zinc/ copper ratio in the serum of patients with cutaneous leishmaniasis in Qom Province, center of Iran. METHODS: Serum levels of zinc and copper were determined by flame atomic absorption spectrophotometer and serum iron concentration was measured by using an Auto Analyzer. The study group consisted of 60 patients with cutaneous leishmaniasis and the control group of 100 healthy volunteers from the same area who were not exposed to cutaneous leishmaniasis. RESULT: There were no statistically significant differences in age and body mass index between the two groups. Serum Zn (P< 0.001) and Fe (P< 0.05) levels were lower in patients with cutaneous leishmaniasis than the control group. We also found serum Cu concentration (P< 0.05) in the patient group was significantly higher than that of the control group. However, zinc/ copper ratio (P< 0.001) was lower in patients with cutaneous leishmaniasis than in the control group. CONCLUSION: Our data indicated that Zn/Cu ratio was significantly lower in patients with CL as compared to the controls. Earlier reports suggest that, this ratio imbalance could be a useful marker for immune dysfunction in leishmaniasis. There was also strong association of Zn, Cu and Fe with CL. It suggests the use of blood zinc, copper, iron concentration and the copper/zinc ratio (Zn/Cu), as a means for estimating the prognosis of CL.