Plasma homocysteine concentration and its relationship with the development of preeclampsia. Effect of prenatal administration of folic acid

The increase of plasmatic homocysteine (Hc) in pregnant women, who later develop preeclampsia/eclampsia, the cause of this increment and its pathogenic role in toxemia of pregnancy, are still controversial. The objectives of the present research were to determine the plasmatic He concentrations during the first and second trimesters of pregnancy and the effect of folic acid administration on these values, and in the prevention of preeclampsia. Ninety six pregnant women of low economic background were studied on the first prenatal consultation: 27 women in the first trimester of pregnancy and 59 in the second. After 8 hours of fasting, venous blood was extracted and each patient was provided with 1 mg folic acid tablets and instructed to ingest one tablet daily, and to come back to the laboratory after three months. Plasma homocysteine and serum folic acid were determined for each patient before and after the folic acid treatment, by using the IMX system (Abbott Lab) and radioimmunoassay, respectively. Basal homocysteine concentrations were 4.0 +/- 2.1 micromol/L and 4.8 +/- 2.1 micromol/L in the first and second trimesters respectively, with no significant modifications after three months of folic acid. Although the degree of desertion from the study was high, it was possible to determine the evolution of 65 pregnancies. Ten of them developed preeclampsia (15.4%). No significant differences were found in Hc concentrations, or the frequency of hyperhomocysteinemia in the different stages of pregnancy, between women with normal gestation and those who developed preeclampsia. The small sample size of these groups, preclude any valid conclusion, however the results do not suggest that Hc concentration or folic acid administration influence the development of toxemia of pregnancy.     

Lower rates of low birthweight and preterm births in the California Black Infant Health Program

OBJECTIVES: The objective of this study was to determine the impact of prenatal interventions in the California Black Infant Health (BIH) Program on low birthweight (LBW) and preterm births (PTB) outcomes. METHODS: A prospective observational study design with a comparison group was used. BIH participants with a delivery recorded between July 1996 and September 1998 were included in the birthweight and PTB analyses. These outcomes for BIH participants who entered the BIH program prior to 32 weeks' gestation (n=1,553) were compared to those of all African-American women in the BIH Program targeted ZIP codes (n=11,633). RESULTS: No statistically significant differences in LBW and PTB were found between the BIH population and the comparison group. However, a comparison of the BIH infant VLBW (<1,500 g) rate (1.9%) with the VLBW rate for the comparison group (3.0%) shows that the BIH rate is 63% of the comparison group rate. For very PTB (<32 weeks), the BIH rate (3.5%) is 81% of the comparison group rate (4.3%). BIH participants had higher risk profiles (pregnancy history, current pregnancy, and psychosocial; p=<0.01) than women in the comparison group. CONCLUSIONS: The BIH Program retained high-risk women in the program to delivery and assisted them with maintenance of prenatal care. Even though the program participants were higher risk, their LBW and PTB outcomes were comparable to the geographic area overall. More importantly, there was a trend among women in the BIH Program toward better outcomes than the comparison group in both VLBW and VPTB.     

A polymorphism in the promoter of UCP2 gene modulates lipid levels in patients with type 2 diabetes

A G/A single nucleotide polymorphism (SNP) in the position -866 of the UCP2 promoter modulates UCP2 expression in adipose tissue and pancreatic beta-cell, and is associated with variations of body mass index (BMI) and insulin secretion in nondiabetic subjects. We investigated associations of this SNP with traits related to obesity, dyslipidemia, and hyperglycemia in patients with type 2 diabetes. The -866 G/A SNP in the UCP2 promoter was genotyped by PCR/RFLP in 681 type 2 diabetic patients. Increased triglyceride (> or = 1.70 mM), total cholesterol (> or = 6.0 mM) and LDL-cholesterol (> or = 3.35 mM) levels were significantly less frequent in homozygous carriers of the G-allele than in homozygous carriers of the A-allele. Odds ratios for the risk of dyslipidemia in GG vs AA carriers were 0.45, 0.57, and 0.50, for triglyceride, total cholesterol and LDL-cholesterol, respectively (all p<0.007). No genetic effects of this polymorphism on the BMI or on traits related to the severity of hyperglycemia were observed. In conclusion, a common polymorphism in the promoter region of the UCP2 gene modulates triglycerides and cholesterol levels in French Caucasian subjects with type 2 diabetes. The implications of this effect in the evolution of type 2 diabetes and its macrovascular complications deserve to be investigated.     

Effects of a brief psychoanalytic intervention for perinatal depression

This pilot study explores the effects of a brief individual psychoanalytic therapy on perinatal depressive symptoms. This intervention is based on the Geneva's mother-infant intervention model. A sample of 129 pregnant women was recruited in Geneva (Switzerland) and screened for depressive symptoms with two instruments: the 'Edinburgh postnatal depression scale' (EPDS) and the 'Dépistage anténatal de la dépression postnatale'. A group of 40 women presenting depressive symptoms (treatment group) participated in a four-session intervention called 'Psychotherapy centred on parenthood (PCP)'. It consists in two antenatal and two postnatal sessions and is focussed on changing problematic representations of parenthood. This treatment group was compared to a control group of 88 women without depressive symptoms and following the usual obstetrical care. The main outcome measure was EPDS at 3 and 6 months after delivery. The 'Global assessment functioning scale' was administered at the end of each therapeutic session. The 'Parent-infant relationship global assessment scale' was administered at the two postnatal sessions in order to explore if PCP was also effective in preventing the potential negative effects of depression on mother-infant relationship. Results show that in the treatment group (N = 31), EPDS scores dropped from 12.8 to 4.8; none of these women met the EPDS cut-off score of 12 at 3 and 6 months postpartum. Mother-infant relationship was well adapted for all 31 dyads at the end of the intervention. These results suggest that PCP is a promising intervention for treating perinatal depression and helping mothers engaging in parenting.     

Possible Anandamide and Palmitoylethanolamide involvement in human stroke

Background  

Endocannabinoids (eCBs) are ubiquitous lipid mediators that act on specific (CB1, CB2) and non-specific (TRPV1, PPAR) receptors. Despite many experimental animal studies proved eCB involvement in the pathogenesis of stroke, such evidence is still lacking in human patients. Our aim was to determine eCB peripheral levels in acute stroke patients and evaluate their relationship with clinical disability and stroke volume.     

PARP inhibitor rucaparib induces changes in NAD levels in cells and liver tissues as assessed by MRS

Poly(adenosine diphosphate ribose) polymerases (PARPs) are multifunctional proteins which play a role in many cellular processes. Namely, PARP1 and PARP2 have been shown to be involved in DNA repair, and therefore are valid targets in cancer treatment with PARP inhibitors, such as rucaparib, currently in clinical trials. Proton magnetic resonance spectroscopy (¹H‐MRS) was used to study the impact of rucaparib in vitro and ex vivo in liver tissue from mice, via quantitative analysis of nicotinamide adenosine diphosphate (NAD⁺) spectra, to assess the potential of MRS as a biomarker of the PARP inhibitor response. SW620 (colorectal) and A2780 (ovarian) cancer cell lines, and PARP1 wild‐type (WT) and PARP1 knock‐out (KO) mice, were treated with rucaparib, temozolomide (methylating agent) or a combination of both drugs. ¹H‐MRS spectra were obtained from perchloric acid extracts of tumour cells and mouse liver. Both cell lines showed an increase in NAD⁺ levels following PARP inhibitor treatment in comparison with temozolomide treatment. Liver extracts from PARP1 WT mice showed a significant increase in NAD⁺ levels after rucaparib treatment compared with untreated mouse liver, and a significant decrease in NAD⁺ levels in the temozolomide‐treated group. The combination of rucaparib and temozolomide did not prevent the NAD⁺ depletion caused by temozolomide treatment. The ¹H‐MRS results show that NAD⁺ levels can be used as a biomarker of PARP inhibitor and methylating agent treatments, and suggest that in vivo measurement of NAD⁺ would be valuable.     

The <Emphasis Type="Italic">NLRP3</Emphasis> and <Emphasis Type="Italic">CASP1</Emphasis> gene polymorphisms are associated with developing of acute coronary syndrome: a case-control study

The protein products of NLRP3 and CASP1 genes are involved in the cleavage of pro-IL-1B and pro-IL-18 leading to the active cytokines, which play an important role in the development of the acute coronary syndrome (ACS). The aim of the present study was to evaluate whether NLRP3 and CASP1 gene polymorphisms are biomarkers of ACS susceptibility in Mexican population. Two polymorphisms of the CASP1 gene [G+7/in6A (rs501192) and A10370-G Exon-6 (rs580253)] and one of the NLRP3 gene [UTR′3 G37562-C (rs10754558)] were genotyped by 5′ exonuclease TaqMan assays in a group of 617 patients with ACS and 609 control individuals. Under recessive model, the CASP1 G+7/in6A polymorphism was associated with an increased risk of developing ACS when compared to healthy controls (OR = 1.76, 95% CI 1.08–2.86, P _Res  = 0.022). In the same way, under recessive model, the CASP1 A10370-G was associated with increased risk of ACS (OR = 1.75, 95% CI 1.07–2.85, P _Res  = 0.025). Moreover, under co-dominant, dominant, over-dominant, and additive models, the NLRP3 UTR′3 G37562-C was associated with a decreased risk of ACS (OR = 0.45, 95%CI 0.22–0.92, P _Co-dom  = 0.006; OR = 0.61, 95%CI 0.44–0.84, P _Dom  = 0.002; OR = 0.67, 95%CI 0.48–0.94, P _Over-dom  = 0.02; and OR = 0.65, 95%CI 0.50–0.94, P _Add  = 0.02, respectively). In summary, this study demonstrates that the G+7/in6A and A10370-G polymorphisms of the CASP1 gene are associated with increased risk of developing ACS, whereas the UTR′3 G37562-C polymorphism of the NLRP3 gene is associated with a decreased risk of developing ACS in Mexican population.     

Reduced frequency of two activating KIR genes in patients with sepsis

Natural killer (NK) cell activity is regulated by activating and inhibitory signals transduced by killer cell immunoglobulin-like receptors (KIR). Diversity in KIR gene repertoire among individuals may affect disease outcome. Sepsis development and severity may be influenced by genetic factors affecting the immune response. Here, we examined sixteen KIR genes and their human leucocyte antigen (HLA) class I ligands in critical patients, aiming to identify patterns that could be associated with sepsis. Male and female patients (ages ranging between 14 and 94 years-old) were included. DNA samples from 211 patients with sepsis and 60 controls (critical care patients with no sepsis) collected between 2004 and 2010 were included and genotyped for KIR genes using the polymerase chain reaction method with sequence-specific oligonucleotide (PCR-SSO), and for HLA genes using the polymerase chain reaction method with sequence-specific primers (PCR-SSP). The frequencies of activating KIR2DS1 and KIR3DS1 in sepsis patients when compared to controls were 41.23% versus 55.00% and 36.49% versus 51.67% (p = 0.077 and 0.037 respectively before Bonferroni correction). These results indicate that activating KIR genes 2DS1 and 3DS1 may more prevalent in critical patients without sepsis than in patients with sepsis, suggesting a potential protective role of activating KIR genes in sepsis.