Moral approval of xenotransplantation in Egypt: associations with religion, attitudes towards animals and demographic factors.

Xenotransplantation has great potential as an alternative to alleviate the shortage of organs for donation. However, given that the animal most suited for xenotransplantation is the pig, there are concerns that people in Muslim countries may be more hesitant to morally approve of these procedures. In this study, the moral approval of xenotransplantation was assessed in a group of 895 participants in Egypt. The results showed that religiosity itself does not predict moral approval of xenotransplantation, but religious identity does, as Muslims are less likely to approve of xenotransplantation than Christians. However, the strongest predictor of moral approval of xenotransplantation was gender, with women displaying less approval. A partial mediating factor in this association was concern for animal welfare. Based on these results, some implications for public policy are discussed.

A disease-modifying treatment for Alzheimer's disease: focus on the trans-sulfuration pathway.

High homocysteine levels in Alzheimer's disease (AD) result from low activity of the trans-sulfuration pathway. Glutathione levels are also low in AD. L-cysteine is required for the synthesis of glutathione. The synthesis of coenzyme A (CoA) requires L-cysteine, which is synthesized via the trans-sulfuration pathway. CoA is required for the synthesis of acetylcholine and appropriate cholinergic neurotransmission. L-cysteine is required for the synthesis of molybdenum-containing proteins. Sulfite oxidase (SUOX), which is a molybdenum-containing protein, could be dysregulated in AD. SUOX detoxifies the sulfites. Glutaminergic neurotransmission could be dysregulated in AD due to low levels of SUOX and high levels of sulfites. L-cysteine provides sulfur for iron-sulfur clusters. Oxidative phosphorylation (OXPHOS) is heavily dependent on iron-sulfur proteins. The decrease in OXPHOS seen in AD could be due to dysregulations of the trans-sulfuration pathway. There is a decrease in aconitase 1 (ACO1) in AD. ACO1 is an iron-sulfur enzyme in the citric acid cycle that upon loss of an iron-sulfur cluster converts to iron regulatory protein 1 (IRP1). With the dysregulation of iron-sulfur cluster formation ACO1 will convert to IRP1 which will decrease the 2-oxglutarate synthesis dysregulating the citric acid cycle and also dysregulating iron metabolism. Selenomethionine is also metabolized by the trans-sulfuration pathway. With the low activity of the trans-sulfuration pathway in AD selenoproteins will be dysregulated in AD. Dysregulation of selenoproteins could lead to oxidant stress in AD. In this article, we propose a novel treatment for AD that addresses dysregulations resulting from low activity of the trans-sulfuration pathway and low L-cysteine.

Treatment-resistant schizophrenia: focus on the transsulfuration pathway.

Treatment-resistant schizophrenia (TRS) is a severe form of schizophrenia. The severity of illness is positively related to homocysteine levels, with high homocysteine levels due to the low activity of the transsulfuration pathway, which metabolizes homocysteine in synthesizing L-cysteine. Glutathione levels are low in schizophrenia, which indicates shortages of L-cysteine and low activity of the transsulfuration pathway. Hydrogen sulfide (H2S) levels are low in schizophrenia. H2S is synthesized by cystathionine ß-synthase and cystathionine γ-lyase, which are the two enzymes in the transsulfuration pathway. Iron-sulfur proteins obtain sulfur from L-cysteine. The oxidative phosphorylation (OXPHOS) pathway has various iron-sulfur proteins. With low levels of L-cysteine, iron-sulfur cluster formation will be dysregulated leading to deficits in OXPHOS in schizophrenia. Molybdenum cofactor (MoCo) synthesis requires sulfur, which is obtained from L-cysteine. With low levels of MoCo synthesis, molybdenum-dependent sulfite oxidase (SUOX) will not be synthesized at appropriate levels. SUOX detoxifies sulfite from sulfur-containing amino acids. If sulfites are not detoxified, there can be sulfite toxicity. The transsulfuration pathway metabolizes selenomethionine, whereby selenium from selenomethionine can be used for selenoprotein synthesis. The low activity of the transsulfuration pathway decreases selenoprotein synthesis. Glutathione peroxidase (GPX), with various GPXs being selenoprotein, is low in schizophrenia. The dysregulations of selenoproteins would lead to oxidant stress, which would increase the methylation of genes and histones leading to epigenetic changes in TRS. An add-on treatment to mainline antipsychotics is proposed for TRS that targets the dysregulations of the transsulfuration pathway and the dysregulations of other pathways stemming from the transsulfuration pathway being dysregulated.

Reward and punishment learning in schizophrenia and bipolar disorder.

Prior studies on reward learning deficits in psychiatric disorders have used probabilistic learning tasks, making it unclear whether impairment is due to the probabilistic nature of the task rather than reward processing. In this study, we tested probabilistic vs. deterministic reward and punishment learning in healthy controls and three patient groups: schizophrenia (SZ), psychotic bipolar disorder (BD), and nonpsychotic BD. Experimental results show that reward learning was impaired in patients with SZ and patients with psychotic BD in the probabilistic learning task compared to patients with nonpsychotic BD and healthy controls. In contrast, punishment learning in the probabilistic task was impaired in patients with nonpsychotic BD compared to the other patient groups and healthy controls. There were no significant differences among all groups in the deterministic learning task scores. We also found that Hamilton Depression Scale scores negatively correlated with probabilistic learning performance. Our data may suggest that reward learning impairment may be due to the nature of the task as well as subtype of BD.