Reliable and powerful laboratory markers of cobalamin deficiency in the newborn: plasma and urinary methylmalonic acid

Background: Diagnosing cobalamin deficiency is critical, given the high prevalence of cobalamin deficiency particularly in developing countries. Measuring serum cobalamin levels is of limited diagnostic sensitivity, in other words its specificity and sensitivity are low. The present study investigated the changes in the levels of metabolic markers – plasma homocysteine, plasma methylmalonic acid (MMA) and urinary MMA – of cobalamin metabolism.

Methods: Plasma cobalamin and serum folic acid were studied in 206 pregnant women over the last four prenatal weeks. Plasma cobalamin, folic acid, homocysteine, MMA from umbilical cord blood and urinary MMA in newborns were studied.

Results: Plasma cobalamin values were low in 66% of the mothers. There was a positive correlation between maternal and neonatal plasma cobalamin values (r?=?0.72, p?<?0.001). B12 was strongly inversely associated with plasma MMA, urine MMA and plasma homocysteine. To predict cobalamin deficiency, sensitivities of plasma MMA, urinary MMA and homocysteine were 96.4%, 95.6% and 88.2%, respectively. And positive predictive values (PPV) were 96.2%, 96.9% and 86% for plasma MMA, urinary MMA and plasma homocysteine levels, respectively.

Conclusion: Plasma MMA and urinary MMA B12 are the most robust markers of cobalamin deficiency. As a non-invasive method, urinary MMA is a sensitive method in demonstrating cobalamin deficiency in the newborn.     

Spectroscopic,antiproliferative and antiradical properties of Cu(II), Ni(II), and Zn(II) complexes with amino acid based Schiff bases

Novel six Cu(II), Ni(II), and Zn(II) complexes with Schiff bases derived from 4-aminobenzoic acid with terephtaldehyde and amino acids (glycine, β-alanine). Structures have been proposed from elemental analysis, UV–Vis, IR, NMR, TGA, DTA, and magnetic measurements. Spectroscopic studies suggest that coordination occurs through azomethine nitrogen, hydroxyl group, and carbonyl oxygen of the ligands to the metal ions. The elemental analyses of the complexes where L is Schiff base ligands, are confined to the stoichiometry of the type M₂L₂(CH₃COO)₂ [M = Cu(II)]; and M₂L(CH₃COO)₂ [M = Ni(II) and Zn(II)]. The cytotoxicity activities of the compounds against human breast carcinoma MCF-7 cell line have been studied. Ligands and their Zn(II) compounds inhibited cell proliferation of MCF-7 cancer cell lines in a dose- and time-dependent manner. The free radical scavenging activity was measured by 1,1-diphenyl-2-picryl-hydrazil. Our results show that the synthesized compounds induced oxidative damage by increasing the lipid peroxidation in yeast since MDA formation was increased, and it could be concluded that the synthesized compounds caused oxidative stress. In addition, the antioxidant activities of the synthesized compounds were very much lower than those of standard antioxidants.     

Pleural fluid neopterin levels in tuberculous pleurisy

OBJECTIVES: Neopterin is produced by stimulated macrophages under the influence of gamma interferon of lymphocyte origin. It is regarded as a biochemical marker of cell-mediated immune response. This study was designed to assess the diagnostic value of pleural fluid neopterin levels in tuberculous pleurisy in comparison with adenosine deaminase activity. DESIGN AND METHODS: Pleural fluid adenosine deaminase (ADA) activity and neopterin levels were measured in 16 patients with tuberculous pleurisy (TP) and 19 patients with malignant pleurisy (MP). ADA activity was determined by a colorimetric method, whereas neopterin levels were determined by a reversed-phase liquid chromatography technique. All values were given as median (min-max). RESULTS: The mean age was 45.43+/-20.39 years in the TP group and 60.42+/-11.02 years in the MP group (p=0.026). The median pleural fluid ADA activity was 51.75 U/L (3.50-62.40 U/L) in the TP group and was 2.30 U/L (1-8.20 U/L) in the MP group. The difference was statistically significant (p<0.001). The median pleural fluid neopterin levels were 13.15 nmol/L (1.86-59.50 nmol/L) and 2.44 nmol/L (0.92-27.60 nmol/L) in the TP group and the MP group, respectively (p=0.021). In order to evaluate the diagnostic value of pleural fluid neopterin concentrations, receiver-operating-characteristic curve analysis was performed. CONCLUSION: Pleural fluid neopterin concentration is significantly higher in TP when compared to MP, however when compared, its clinical use as a diagnostic marker is not valuable as ADA.     

Contribution of diffusion‐weighted imaging to dynamic contrast‐enhanced MRI in the characterization of papillary breast lesions

Papillary lesions have a broad spectrum of appearances on magnetic resonance imaging (MRI ). The purpose of this study was to evaluate whether apparent diffusion coefficient (ADC ) values of papillary lesions can be used to characterize lesion as benign or malignant. This retrospective study included 29 papillary lesions. Diagnostic values of dynamic contrast‐enhanced MRI (DCE‐MRI), DWI ‐ADC , and DCE ‐MRI plus DWI ‐ADC were separately calculated. The malignant papillary lesions (0.744×10^?3 mm²/s) exhibited significantly lower mean ADC values than the benign lesions (1.339×10^?3 mm²/s). Addition of DWI to standard DCE ‐MRI provided 100% sensitivity. We hypothesized that this combination may prevent unnecessary excisional biopsies.     

Behavior and serotonergic disorders in rats exposed prenatally to valproate: A model for autism

In order to explore whether some aspects of the autistic phenotype could be related to impairment of the serotonergic system, we chose an animal model which mimics a potential cause of autism, i.e. rats exposed to valproate (VPA) on the 9th embryonic day (E9). Previous studies have suggested that VPA exposure in rats at E9 caused a dramatic shift in the distribution of serotonergic neurons on postnatal day 50 (PND50). Behavioral studies have also been performed but on rats that were exposed to VPA later (E12.5). Our aim was to test whether VPA exposure at E9 induces comparable behavioral impairments than at E12.5 and causes serotonergic impairments which could be related to behavioral modifications. The results showed significant behavioral impairments such as a lower tendency to initiate social interactions and hyperlocomotor activity in juvenile male rats. The serotonin levels of these animals at PND50 were decreased (−46%) in the hippocampus, a structure involved in social behavior. This study suggests that VPA could have a direct or indirect action on the serotonergic system as early as the progenitor cell stage. Early embryonic exposure to VPA in rats provides a good model for several specific aspects of autism and should help to continue to explore pathophysiological hypotheses.     

Novel Aminomethylindole Derivatives as Inhibitors of pp60c‐Src Tyrosine Kinase: Synthesis and Biological Activity

The pp60^c‐Src is one of the ubiquitously expressed Src family kinases and has important functions in malignant cells, including regulation of cell division, growth factor signaling, and movement. Therefore, investigating new small molecule inhibitors of pp60^c‐Src is important to discover and develop novel therapeutics for cancer and metastasis. Moreover, some of the small molecule inhibitors that do not qualify for therapeutic use may become very useful tool to explore the role of Src kinase in normal cells as well as in a variety of disease models. Our continuous efforts to find novel inhibitors of pp60^c‐Src aimed for therapeutic and research use, we synthesized newly designed aminomethylindole derivatives as novel small molecule inhibitors and investigated their inhibitory effect on pp60^c‐Src tyrosine kinase. Here, we report one potential inhibitor of the pp60^c‐Src from five active molecules of all nine compounds, which were synthesized and screened for the biological activity of the molecules against pp60^c‐Src target.     

Griscelli syndrome: Report of Three Cases

The clinical features of three children with Griscelli syndrome and autopsy findings of two are presented. The patients were 5 years, 9 months, and 3 months old, respectively. Clinical features included partial albinism, hepatosplenomegaly, and various neurological symptoms. Light and electron microscopic studies of the skin were compatible with Griscelli syndrome. Postmortem examination of the viscera and central nervous system revealed lymphohistiocytic infiltration with erythrophagocytosis. Bilateral diffuse involvement of the central nervous system, cranial nerve, and spinal cord was detected in both cases.     

The effect of adrenalectomy on leptin levels and some metabolic parameters in rats with diet-induced obesity

Recently, there has been many investigations on the relationship between leptin and obesity, which is the main health problem in developed countries. In some reports, it has been claimed that the adrenalectomy has lead to weight loss and thus prevented obesity induced in rodents in various ways. It has also been accepted that diet-induced obesity in animals is very similar to obesity in humans beings. In this study, obesity has been developed with high-calorie diet given for 8 weeks in Sprague-Dawley rats. Then, it has been investigated how leptin and some metabolic parameters change in blood samples obtained from rats 15 d after adrenalectomy. Leptin levels was determined with Radio Immun Assay (RIA, Linco Research Co) method. Our study showed that, there were statistically significant increases in leptin (p<0.001), glucose (p<0.05), triglyceride (p<0.01) levels in diet-induced obese rats (n=19) when compared with the findings of control rats, lean ones (n=16), (Tables 3, 4). Adrenalectomy led to decreased serum leptin (p<0.001) and triglyceride (p<0.01) levels both in the obese and lean rats (Table 5). As a conclusion, it could be claimed that the decrease in leptin levels may be attributed to reduced adipose tissue due to adrenalectomy. On the other hand, the decreases in glucose and triglyceride levels might be the consequence of reduced lipogenesis and impaired gluconeogenesis with the effect of adrenalectomy. It was concluded that adrenalectomy might prevent obesity by affecting leptin and intermediate metabolism.