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     

C-reactive protein induces phosphorylation of insulin receptor substrate-1 on Ser<Superscript>307</Superscript> and Ser<Superscript>612</Superscript> in L6 myocytes,thereby impairing the insulin signalling pathway that promotes glucose transport

Aims/hypothesis C-reactive protein (CRP) is associated with insulin resistance and predicts development of type 2 diabetes. However, it is unknown whether CRP directly affects insulin signalling action. To this aim, we determined the effects of human recombinant CRP (hrCRP) on insulin signalling involved in glucose transport in L6 myotubes. Materials and methods L6 myotubes were exposed to endotoxin-free hrCRP and insulin-stimulated activation of signal molecules, glucose uptake and glycogen synthesis were assessed. Results We found that hrCRP stimulates both c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK)1/2 activity. These effects were paralleled by a concomitant increase in IRS-1 phosphorylation at Ser³⁰⁷ and Ser⁶¹², respectively. The stimulatory effects of hrCRP on IRS-1 phosphorylation at Ser³⁰⁷ and Ser⁶¹² were partially reversed by treatment with specific JNK and ERK1/2 inhibitors, respectively. Exposure of L6 myotubes to hrCRP reduced insulin-stimulated phosphorylation of IRS-1 at Tyr⁶³², a site essential for engaging p85 subunit of phosphatidylinositol-3 kinase (PI-3K), protein kinase B (Akt) activation and glycogen synthase kinase-3 (GSK-3) phosphorylation. These events were accompanied by a decrease in insulin-stimulated glucose transporter (GLUT) 4 translocation to the plasma membrane, glucose uptake and glucose incorporation into glycogen. The inhibitory effects of hrCRP on insulin signalling and insulin-stimulated GLUT4 translocation were reversed by treatment with JNK inhibitor I and the mitogen-activated protein kinase inhibitor, PD98059. Conclusions/interpretation Our data suggest that hrCRP may cause insulin resistance by increasing IRS-1 phosphorylation at Ser³⁰⁷ and Ser⁶¹² via JNK and ERK1/2, respectively, leading to impaired insulin-stimulated glucose uptake, GLUT4 translocation, and glycogen synthesis mediated by the IRS-1/PI-3K/Akt/GSK-3 pathway.     

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.     

Decreased inhibitory activity of PKC in OCD patients after six months of treatment

We investigated 5-HT reuptake and protein kinase of type C (PKC) activation in platelets of 14 OCD patients at baseline and after six months of treatment with different serotonin (5-HT) reuptake inhibitors (SRIs). The results showed that all SRIs provoked a significant increase in both the maximal velocity (V(max)) and the Michaelis-Menten constant (K(m)) of 5-HT reuptake, as compared with baseline values. The activation of PKC by means of 4-beta-12-tetradecanoylphorbol 13-acetate provoked a significant decrease in V(max) values, but the effect was not as evident as at baseline. These findings could indicate that, in OCD patients, SRIs increase the rate of reuptake and decrease the inhibitory effect of PKC and that the two phenomena may be linked, the first perhaps depending upon the second.     

Effects of CRL 41034 on the adrenergic neuroeffector interaction in the canine saphenous vein

Experiments were designed to determine the effect of CRL 41034, a buflomedil analogue, on the adrenergic responsiveness of canine veins. Rings of saphenous vein (without endothelium) were suspended for isometric tension recording in modified Krebs-Ringer bicarbonate solution at 37 degrees C. CRL 41034 produced a concentration-dependent inhibition of the contractions evoked by the alpha adrenergic agonists norepinephrine, phenylephrine and UK 14304 which was insensitive to the blockade of neuronal uptake by cocaine. CRL 41034 was more potent in inhibiting the concentration-dependent contractions evoked by UK 14304 than those by phenylephrine and the antagonism it caused against the response to UK 14304 fulfilled the criteria for competitivity. CRL 41034, at 10(-5) M significantly depressed, and at 10(-4) M abolished the contractions induced by electrical stimulation of the adrenergic nerves and those evoked by the indirect sympathomimetic amine tyramine. Strips of canine saphenous vein were superfused after incubation with [3H] norepinephrine. During sympathetic nerve activation, CRL 41304 increased the stimulation-evoked overflow of [3H] norepinephrine and 3-methoxy-4-dihydroxyphenylglycol; in the presence of rauwolscine the compound only increased the stimulation-evoked overflow of 3,4-dihydroxyphenylglycol. These experiments suggest that the major vascular effects of CRL 41034 in canine veins are blockade of alpha 2-adrenoceptors on vascular smooth muscle, and inhibition of prejunctional alpha 2-adrenoceptors on adrenergic nerve endings.