The interactions of Cobalt(II) with mitochondria from rat liver

The interactions of Co2+ with mitochondria have been investigated. The results indicate that Co2+ inhibits ATP synthesis. Further investigations into ATP synthesis mechanisms indicated that inhibition is due to the opening of a transmembrane pore. The opening of this pore causes the collapse of the high-energy intermediate where, under a pH and a potential gradient, the energy is stored and subsequently utilized to form ATP from ADP

Status of HIV and hepatitis C virus infections among prisoners in the Middle East and North Africa: review and synthesis.

INTRODUCTION: The status of HIV and hepatitis C virus (HCV) infections among incarcerated populations in the Middle East and North Africa (MENA) and the links between prisons and the HIV epidemic are poorly understood. This review synthesized available HIV and HCV data in prisons in MENA and highlighted opportunities for action. METHODS: The review was based on data generated through the systematic searches of the MENA HIV/AIDS Epidemiology Synthesis Project (2003 to December 15, 2015) and the MENA HCV Epidemiology Synthesis Project (2011 to December 15, 2015). Sources of data included peer-reviewed publications and country-level reports and databases. RESULTS AND DISCUSSION: We estimated a population of 496,000 prisoners in MENA, with drug-related offences being a major cause for incarceration. Twenty countries had data on HIV among incarcerated populations with a median prevalence of 0.6% in Afghanistan, 6.1% in Djibouti, 0.01% in Egypt, 2.5% in Iran, 0% in Iraq, 0.1% in Jordan, 0.05% in Kuwait, 0.7% in Lebanon, 18.0% in Libya, 0.7% in Morocco, 0.3% in Oman, 1.1% in Pakistan, 0% in Palestine, 1.2% in Saudi Arabia, 0% in Somalia, 5.3% in Sudan and South Sudan, 0.04% in Syria, 0.05% in Tunisia, and 3.5% in Yemen. Seven countries had data on HCV, with a median prevalence of 1.7% in Afghanistan, 23.6% in Egypt, 28.1% in Lebanon, 15.6% in Pakistan, and 37.8% in Iran. Syria and Libya had only one HCV prevalence measure each at 1.5% and 23.7%, respectively. There was strong evidence for injecting drug use and the use of non-sterile injecting-equipment in prisons. Incarceration and injecting drugs, use of non-sterile injecting-equipment, and tattooing in prisons were found to be independent risk factors for HIV or HCV infections. High levels of sexual risk behaviour, tattooing and use of non-sterile razors among prisoners were documented. CONCLUSIONS: Prisons play an important role in HIV and HCV dynamics in MENA and have facilitated the emergence of large HIV epidemics in at least two countries, Iran and Pakistan. There is evidence for substantial but variable HIV and HCV prevalence, as well as risk behaviour including injecting drug use and unprotected sex among prisoners across countries. These findings highlight the need for comprehensive harm-reduction strategies in prisons

Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis

A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (∼0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD

Involvement of intracellular Na+\mathsf{^+} accumulation in Hg+2\mathsf{^{+2}} or Cd+2\mathsf{^{+2}} induced cytotoxicity

Previously we showed that hepatocyte lysis induced by Hg$^{+2}$ or Cd$^{+2}$ could be partly attributed to mitochondrial toxicity [1, 2]. Similar changes in Na$^+$ homeostasis induced when Cd$^{+2}$ or Hg$^{+2}$ was incubated with hepatocytes. Cd$^{+2}$ or Hg$^{+2}$ induced cytotoxicity were prevented by Na$^+$ omission from the media or by the addition of the Na$^+$/H$^+$ exchange inhibitor 5-(N, N-dimethyl)-amiloride. Furthermore the omission of CI$^-$ from the media or 2 addition of glycine, a CI$^-$ channel blocker also prevented Cd$^{+2}$ or Hg$^{+2}$ induced hepatocyte toxicity. A hypotonic media also increased Cd$^{+2}$ or Hg$^{+2}$ induced hepatocyte cytotoxicity. This suggests that Cd$^{+2}$ or Hg$^{+2}$ cytotoxicity could be partly attributed to disruption of cell volume regulation mechanisms. The increased osmotic load caused by the uncontrolled accumulation of intracellular Na$^+$ in Cd$^{+2}$ or Hg$^{+2}$ treated hepatocytes likely resulted from the activation of Na$^+$/H$^+$ exchanger and the Na$^+$/HCO3$^-$ cotransporter by the acidosis and ATP depletion caused by mitochondrial toxicity