Clinical Chemistry and Laboratory Medicine

The effect of solvent conditions on the aggregation of IgM in serum specimens from patients with macroglobulinemia was studied by a turbidimetric procedure. Aggregation of IgM varied considerably among the samples and was affected by a number of experimental parameters. In general, IgM aggregation was more pronounced under acidic conditions and in solvents with low ionic strength. The presence of watermiscible organic solvents also promoted aggregation. Based on these studies, it was concluded that the major force involved in the formation of immunoglobulin aggregates in the serum of patients with macroglobulinemia was electrostatic, rather than hydrophobic, interactions. A number of additives known to prevent protein aggregation were evaluated for their effectiveness in inhibiting IgM aggregation. The only additives that were shown to inhibit or reduce IgM aggregation were charged molecules, such as arginine, sodium chloride, ethylenediamintetraacetic acid and quaternary ammonium β-cyclodextrin. Some of these charged additives were also effective in dissociating the IgM aggregates once they were formed, even in the presence of detergent.

Background: Nitric oxide (NO) is known to be a signaling molecule with many physiogical functions including apoptotic process regulation. Since apoptosis may contribute to the pathophysiology of schizophrenia, this study was undertaken to determine the plasma concentrations of NO in schizophrenics.

Methods: Nitrite/nitrate (NO₂ ^–/NO₃ ^–) concentrations were measured in plasma from 40 patients with schizophrenia, and 36 age- and gender-matched healthy persons using a colorimetric test.

Results: Plasma NO₂ ^–/NO₃ ^– concentrations were significantly higher in patients with schizophrenia (102.8±34.7 μmol/L, p<0.0001) than in controls (69.2±13.2 μmol/L). Also, mean NO₂ ^–/NO₃ ^– values in female patients and controls were significantly higher (118.2±44.7 μmol/L, p<0.001; 74.8±16.1 μmol/L, p<0.05, respectively) compared to males (94.7±25.3 μmol/L, 67.6±10.8 μmol/L). Significant correlation was seen between plasma NO₂ ^–/NO₃ ^– concentrations and heredity, number of episodes and peripheral blood mononuclear cell (PBMC) caspase-3 activity, which was significantly higher in patients than in controls (p<0.05). There was no significant difference in NO₂ ^–/NO₃ ^– concentrations between patients with different Positive and Negative Syndrome Scale (PANSS) scores or between patients treated with haloperidol (97.2±31.2 μmol/L) and those treated with other atypical antipsychotic drugs (109.8±33.7 μmol/L). Both parameters showed no significant differences between smokers and non-smokers.

Conclusions: This study showed that plasma NO₂ ^–/NO₃ ^– concentrations were significantly increased in patients with schizophrenia, being significantly higher in female than male patients, and showing a significant correlation with heredity, number of episodes and PBMC caspase-3 activity. These results suggest that NO could be considered an inducer or regulator of apoptosis in patients with schizophrenia.

Clin Chem Lab Med 2010;48:89–94.

Pancreatic cancer is considered one of the most lethal cancers being the fourth leading cause of cancer deaths in adults in the United States because of the lack of early signs and symptoms and the lack of early detection. Pancreatic ductal adenocarcinoma (PDAC) is the most common histological type among pancreatic cancers, representing 80%–90% of all solid tumors of the pancreas. The majority of PDAC develops from three precursor lesions: pancreatic intraepithelial neoplasia, intraductual papillary mucinous neoplasm and mucinous cystic neoplasm. Although histologic tissue evaluation remains the gold standard for diagnosis, endoscopic ultrasound-guided fine needle aspiration has become the preferred modality for obtaining pathologic confirmation. At Dartmouth-Hitchcock Medical Center (DHMC),we have developed and validated a microRNA (miRNA) panel for patients with pancreatic diseases that can be used in association with the gold standard method for diagnosis. miRNAs have an important role in biological processes, such as apoptosis, metabolism, cell growth and differentiation. In cancer, miRNAs can be classified as either oncogenic or tumor suppressor according to their function in the carcinogenic process. In this study, we describe the expression of many miRNA in benign and malignant pancreatic tissues as well as their clinical significance. For this reason, miRNAs have been considered potential biomarkers of pancreatic diseases that could potentially contribute to an early diagnosis, predict disease progression, accurately monitor disease, contribute to better treatment strategies and reduce mortality by improving disease management.

CYP2C9, an isoform of the cytochrome P450 enzyme, is involved in the metabolism of most of the drugs of choice for the treatment of thromboembolic disorders. Functional polymorphism is associated with two variant alleles (alleles