Serum Serotonin Abnormality in Depression

Background

Serotonin plays an important role in treatment of depression. We evaluated the clinical correlates of plasma serotonin levels in depressed patients before and after treatment.

Methods

Study sample comprised of 40 patients diagnosed on ICD-10 diagnostic criteria, and an equal number of healthy matched controls. Subjects were evaluated on Beck''s Depression Inventory (BDI) and Suicide Ideation Scale (SIS), before and after the treatment. Blood samples were collected from all the cases and controls before starting the antidepressant medication with selective serotonin reuptake inhibitors (SSRI''s). Serum serotonin levels were measured before and after treatment.

Result

Significant differences in scores before and after the intervention on BDI, SIS and serotonin levels of cases and controls (p<.000) were noted. Correlation between the serum serotonin levels before and after the treatment, and between the rating scales did not reveal significant association (p > 0.05). Patients with suicidal intentions had lower levels of serotonin. The scores changed after intervention.

Conclusion

Treatment with SSRI''s had shown significant changes in clinical conditions. However these changes did not relate significantly with serum serotonin levels.Key Words: Serotonin, Depression, Selective serotonin reuptake inhibitors     

Pharmacophore-based 3D-QSAR of HIF-1 inhibitors

(Aryloxyamino)benzoic acids and nicotinic/isonicotinic acids represent an important new class of small molecules that inhibit the activation of Hypoxia-Inducible Factor (HIF)-1. In order to understand the factors affecting inhibitory potency of HIF-1 inhibitors, 3 dimensional-quantitative structure activity relationship (3D-QSAR) studies were performed. Since no receptor structure are available, the pharmacophore-based alignment was used for comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). The CoMFA and CoMSIA models gave reasonable statistics (CoMFA: q² = 0.564, r²=0.945; CoMSIA: q² = 0.575, r²=0.929). Both CoMFA and CoMSIA results indicate that the steric interaction is a major factor, while CoMSIA suggests importance of hydrogen bonding. These findings about steric and H-bonding effects can be useful to design new inhibitors. Equally contributed in this work.     

Validation of MCADD newborn screening

Medium‐chain acyl‐CoA dehydrogenase deficiency (MCADD) represents a potentially fatal fatty acid β‐oxidation disorder. Newborn screening (NBS) by tandem mass spectrometry (MS/MS) has been implemented worldwide, but is associated with unresolved questions regarding population heterogeneity, burden on healthy carriers, cut‐off policies, false‐positive and negative rates. In a retrospective case‐control study, 333 NBS samples showing borderline acylcarnitine patterns but not reaching recall criteria were genotyped for the two most common mutations (c.985A>G/c.199C>T) and compared with genotypes and acylcarnitines of 333 controls, 68 false‐positives, and 34 patients. c.985A>G was more frequently identified in the study group and false‐positives compared to controls (1:4.3/1:2.3 vs. 1:42), whereas c.199C>T was found more frequently only within the false‐positives (1:23). Biochemical criteria were devised to differentiate homozygous (c.985A>G), compound heterozygous (c.985A>G/c.199C>T), and heterozygous individuals. Four false‐negatives were identified because our initial algorithm required an elevation of octanoylcarnitine (C₈) and three secondary markers in the initial and follow‐up sample. The new approach allowed a reduction of false‐positives (by defining high cut‐offs: 1.4 μmol/l for C₈; 7 for C₈/C₁₂) and false‐negatives (by sequencing the ACADM gene of few suspicious samples). Our validation strategy is able to differentiate healthy carriers from patients doubling the positive predictive value (42→88%) and to target NBS to MCADD‐subsets with potentially higher risk of adverse outcome. It remains controversial, if NBS programs should aim at identifying all subsets of all diseases included. Because the natural course of milder variants cannot be assessed by observational studies, our strategy could serve as a general model for evaluation of MS/MS‐based NBS.     

Italian healthcare workers' views on mandatory vaccination

Background  

Mandatory vaccination has contributed to the success of immunisation programmes but voluntary vaccination allows people to be responsible for their own health. There are benefits from both policies and the arguments between them remain subject to debate within and without the scientific community, both nationally and internationally. The aim of this study is to assess the opinions of those who actually work in the Vaccination Service.     

COX2 and p53 risk-alleles coexist in COPD

BACKGROUND: Cigarette smoke stimulates airway epithelial cells to release pro-inflammatory cytokines which influence various inflammation-related genes, including COX2, whereas p53 expression is known to alter in such a condition. Since both the genes share several common physiological functions including inflammation and oxidative stress, we investigated within gene and gene-gene interactions towards susceptibility to the disease. METHOD: In a prospective gene-association study we conducted PCR-RFLP for genotyping the COX2 -765G/C and 8473T/C and p53 72Pro/Arg polymorphisms in 229 COPD patients and 147 healthy controls. RESULTS: The -765GC+CC genotypes of COX2 and Pro/Pro+Pro/Arg genotypes of p53 were prevalent in patients with significant odds ratio, 2.05 and 2.30, respectively (p=0.001; p=0.009, respectively), as a consequence, the -765C and 72Pro alleles were prevalent (p相似文献   

Assessment of perioperative transfusion therapy and complications in sickle cell disease patients undergoing surgery

BACKGROUND: Perioperative blood transfusion is usually given to sickle cell disease patients to reduce or prevent perioperative morbidity. Assessment of such a practice was the subject of our study. METHODS: A retrospective one year survey of sickle cell disease patients undergoing surgery at Salmaniya Medical Complex, Bahrain was conducted. The medical records were reviewed to characterize the surgical procedure, transfusion management and perioperative complications. RESULTS: 85 sickle cell disease patients who underwent surgery were studied. Preoperatively, 21.2% had exchange transfusion (ETX), 24.7% had simple transfusions (STX) and 54.1% had no transfusion (NTX). 14.1% of all patients had postoperative complications, and 50% of those, had complications from the laparoscopic cholecystectomy group. The incidence of sickle cell crisis postoperatively was 22.2% in ETX group, 9.5% in STX group and 4.34% in the NTX group. The incidence of acute chest syndrome postoperatively was found to be 5.55% in the ETX group, 4.76% in the STX group and 4.34% in the NTX group. No intraoperative complications were recorded in all groups. All patients who had postoperative complications had a preoperative HBSS > 40%. CONCLUSION: Exchange transfusion does not prevent perioperative complications of sickle cell disease patients. HBSS > 40% carries a higher risk of postoperative complications.     

Targeting HER-2/neu in early breast cancer development using dendritic cells with staged interleukin-12 burst secretion

Overexpression of HER-2/neu (c-erbB2) is associated with increased risk of recurrent disease in ductal carcinoma in situ (DCIS) and a poorer prognosis in node-positive breast cancer. We therefore examined the early immunotherapeutic targeting of HER-2/neu in DCIS. Before surgical resection, HER-2/neu(pos) DCIS patients (n = 13) received 4 weekly vaccinations of dendritic cells pulsed with HER-2/neu HLA class I and II peptides. The vaccine dendritic cells were activated in vitro with IFN-gamma and bacterial lipopolysaccharide to become highly polarized DC1-type dendritic cells that secrete high levels of interleukin-12p70 (IL-12p70). Intranodal delivery of dendritic cells supplied both antigenic stimulation and a synchronized preconditioned burst of IL-12p70 production directly to the anatomic site of T-cell sensitization. Before vaccination, many subjects possessed HER-2/neu-HLA-A2 tetramer-staining CD8(pos) T cells that expressed low levels of CD28 and high levels of the inhibitory B7 ligand CTLA-4, but this ratio inverted after vaccination. The vaccinated subjects also showed high rates of peptide-specific sensitization for both IFN-gamma-secreting CD4(pos) (85%) and CD8(pos) (80%) T cells, with recognition of antigenically relevant breast cancer lines, accumulation of T and B lymphocytes in the breast, and induction of complement-dependent, tumor-lytic antibodies. Seven of 11 evaluable patients also showed markedly decreased HER-2/neu expression in surgical tumor specimens, often with measurable decreases in residual DCIS, suggesting an active process of "immunoediting" for HER-2/neu-expressing tumor cells following vaccination. DC1 vaccination strategies may therefore have potential for both the prevention and the treatment of early breast cancer.     

Severe fetal anemia caused by anti-Jra: Burst forming unit-erythroid colony formation inhibition assay suggesting possible erythroid suppression mechanism

Background

The Jr blood group system includes a single, high-prevalence antigen, Jr^a, encoded by the ABCG2 gene. The impact of anti-Jr^a in pregnancy is variable, ranging from no clinical effect to severe anemia including some fetal deaths. Case reports have postulated that anti-Jr^a mediated fetal anemia is poorly hemolytic, suggesting other mechanisms of anemia may be involved.

Study Design and Methods

We describe the case of severe anti-Jr^a mediated fetal anemia. At Canadian Blood Services laboratories, maternal anti-Jr^a was tested for phagocytic activity via a monocyte monolayer assay (MMA) and erythroid suppression via inhibition of burst forming unit-erythroid (BFU-E) colony formation assays. The New York Blood Center sequenced exons 4 and 7 of the ABCG2 gene.

Results and Discussion

Sequencing of exons 4 and 7 of the ABCG2 gene revealed maternal compound heterozygosity for two nonsense mutations at exon 7 (c.706 C > T and c.784G > T). Fetal sequencing revealed the c.706C > T polymorphism. The MMA showed a borderline phagocytic index (around the cutoff of five for both donor segments tested [5 ± 1 and 7 ± 3]). The BFU-E colony formation inhibition assay suggested a dose-dependent inhibition of BFU-E colony formation with inhibition percentages of 4%, 11%, and 43% at maternal serum concentrations of 2%, 5%, and 10%, respectively. Our findings support the hypothesis that anti-Jr^a may impair erythropoiesis leading to clinically significant fetal/neonatal anemia. A referral to maternal fetal medicine is recommended if anti-Jr^a is detected in pregnancy, regardless of the titer.