One of the contributory causes of colon cancer is the negative effect of reactive oxygen species on DNA repair mechanisms. Currently, there is a growing support for the concept that oxidative stress may be an important etiological factor for carcinogenesis. The purpose of this review is to elucidate the role of oxidative stress in promoting colorectal carcinogenesis and to highlight the potential protective role of antioxidants. Several studies have documented the importance of antioxidants in countering oxidative stress and preventing colorectal carcinogenesis. However, there are conflicting data in the literature concerning its proper use in humans, since these studies did not yield definitive results and were performed mostly in vitro on cell populations, or in vivo in experimental animal models.

Alkaptonuria is often diagnosed clinically with episodes of dark urine, biochemically by the accumulation of peripheral homogentisic acid and molecularly by the presence of mutations in the homogentisate 1,2-dioxygenase gene (HGD). Alkaptonuria is invariably associated with HGD mutations, which consist of single nucleotide variants and small insertions/deletions. Surprisingly, the presence of deletions beyond a few nucleotides among over 150 reported deleterious mutations has not been described, raising the suspicion that this gene might be protected against the detrimental mechanisms of gene rearrangements. The quest for an HGD mutation in a proband with AKU revealed with a SNP array five large regions of homozygosity (5–16 Mb), one of which includes the HGD gene. A homozygous deletion of 649 bp deletion that encompasses the 72 nucleotides of exon 2 and surrounding DNA sequences in flanking introns of the HGD gene was unveiled in a proband with AKU. The nature of this deletion suggests that this in-frame deletion could generate a protein without exon 2. Thus, we modeled the tertiary structure of the mutant protein structure to determine the effect of exon 2 deletion. While the two β-pleated sheets encoded by exon 2 were missing in the mutant structure, other β-pleated sheets are largely unaffected by the deletion. However, nine novel α-helical coils substituted the eight coils present in the native HGD crystal structure. Thus, this deletion results in a deleterious enzyme, which is consistent with the proband’s phenotype. Screening for mutations in the HGD gene, particularly in the Middle East, ought to include this exon 2 deletion in order to determine its frequency and uncover its origin.

Background:Coronary heart disease (CHD) is a leading cause of premature death in patients with schizophrenia. CHD risk in Lebanese patients with schizophrenia remains unknown.Objectives:To (i) evaluate CHD risk of patients with schizophrenia in Lebanon; and (ii) detect the modifiable and non-modifiable factors affecting this risk.Methods:Cross-sectional study of 329 patients with schizophrenia aged 20–75 years. Ten-year hard CHD risk was calculated using the Framingham risk score. A logistic regression was conducted taking the dichotomous hard CHD (<10% and ≥10%) as the dependent variable.Results:Ten-year hard CHD risk was low (<10%) in 60.8% of patients, intermediate (10–20%) in 31.6%, and high (>20%) in 7.6%. Multivariate analysis showed that the mean 10-year hard CHD risk was 8.76±6.92 (10.82±6.83 in men and 3.18±2.90 in women). Ten-year hard CHD risk was higher in patients with the metabolic syndrome (odds ratio [OR] 2.67, confidence interval [CI] 1.54–4.64), a longer duration of schizophrenia (OR 1.03, CI 1.01–1.05), a history of other medical illnesses (OR 2.02, CI 1.18–3.47), and in those participating in art therapy (OR 2.13, CI 1.25–3.64) or therapeutic education (OR 1.93, CI 0.93–4.01). Ten-year hard CHD risk was lower in patients receiving risperidone (OR 0.23, CI 0.08–0.68), any anti-epileptic (OR 0.41, CI 0.24–0.73), or any benzodiazepine (OR 0.33, CI 0.17–0.66) medication.Conclusion:CHD is prevalent in patients with schizophrenia in Lebanon. Physicians are recommended to monitor the components of the metabolic syndrome to identify patients with increased risk of cardiovascular diseases.

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