Studies on the Level of Natural Antibodies Reactive with Various Tumor Cells during Urethane Carcinogenesis in BALB/c Mice

Serum from young normal BALB/c mice was found to contain IgM antibodies able tomediate complement-dependent lysis of certain syngeneic or allogeneic tumor target cells. The titer of such naturally occurring antitumor antibodies (NATA) was found to increase with aging.A longitudinal serological study comparing the cytotoxicity potential of NATA fromnormal and from urethan-treated BALB/c mice was performed. It was found that urethan-treated mice that did not develop primary lung-adenomas within the duration of the experi-ment had significantly lower NATA titers, against one out of 4 target cells assayed, than urethan-treated animals that developed lung adenomas. This difference was evident in two independent experiments. The results suggested that the lower NATA activity of the urethan-treated mice that did not develop tumors existed even before exposure to the carcinogenic insult. This raises the possibility that certain populations could be segregated according to their natural antibody profile into those individuals which will develop primary tumors within a certain period if exposed to a subthreshold amount of carcinogen, and those which will not.     

Environmental lead and childhood blood lead levels in US children: NHANES, 1999–2006

Although blood lead levels in the United States have fallen dramatically since 1980, there remain subgroups of children with high blood lead levels. We assessed the relationship between environmental lead sources and blood lead levels in children ages 1 to 5 years from the National Health and Nutrition Examination Survey (NHANES), 1999–2006. Modeled ambient air lead levels and industrial lead releases at the census-tract level were assigned to each child's residence with adjustment for confounding factors. Of 3,223 children, 272 (8.4%) had blood lead levels ≥ 5 ug/dL. Industrial releases (2,252 vs 1,696 lbs/mi²) and ambient air lead levels (2.28 vs 1.75 ng/m³) were greater in exposed versus unexposed children. For every 10,000 lb/mi² increase in inverse distance squared weighted exposure, there was a 1.13% increase (95% CI: 0.45%, 1.81%) in blood lead (p = .001).     

Preparation-free method can enable rapid surfactant screening during industrial processing of influenza vaccines

Triton X-100 (TX-100) is the most common surfactant used to split viruses during the production of influenza split-virus vaccines. It is a mild surfactant not known to denature the viral proteins; this property makes TX-100 useful for maintaining antigen conformational structure, and, as an added benefit, for partially stabilizing vaccine formulations against protein aggregation. Despite its benefits, TX-100 needs to be filtered out after virus splitting has been achieved, due to its toxicity in large quantities. Accordingly, residual TX-100 presence in vaccine formulations has implications for both formulation stability and safety, necessitating both accurate screening during processing to guide decision-making about filtration repeats and accurate quantitation in the final product. Accurate HPLC-based methods are used successfully for the latter but their use for routine screening during processing is far from ideal because they often require extensive sample preparation and are fairly slow, complicated and costly. Here, “deconstruction” of UV–Vis absorption spectra into components corresponding to different absorbing “species” is demonstrated as a novel and viable method for routine TX-100 screening in vaccine samples from different industrial processing steps. This method is fairly accurate and, more importantly, preparation-free, rapid, simple/user-friendly and comparatively inexpensive. It is evaluated in depth in terms of applicability conditions, limitations and potential for high-throughput adaptation as well as generalization to other complex biopharmaceutical formulations.     

In silico study of naphtha [1, 2-d] thiazol-2-amine with adenosine A2A receptor and its role in antagonism of haloperidol-induced motor impairments in mice

Loss of dopaminergic nigrostriatal neurons in the substantia nigra leads to Parkinson's disease (PD). Adenosine A_2A receptors (A_2ARs) have been anticipated as novel therapeutic target for PD. A_2ARs potentiate locomotor behavior and are predominantly expressed in striatum. Naphtha [1, 2-d] thiazol-2-amine (NATA), a tricyclic thiazole have been studied as new anti-Parkinsonian compound. AutoDock analysis and pharmacophore study of NATA with known A_2AR antagonists explicit its efficacy as a possible adenosine receptor antagonist. In vivo pharmacology of NATA showed reduction of haloperidol (HAL)-induced motor impairments in Swiss albino male mice. Relatively elevated levels of dopamine in NATA pre-treated mice are suggestive of its possible role as neuromodulator in PD.     

Evaluation of the agreement between modeled and monitored ambient hazardous air pollutants in California

Elevated breast cancer incidence rates in urban areas have led to speculation regarding the potential role of air pollution. In order to inform the exposure assessment for a subsequent breast cancer study, we evaluated agreement between modeled and monitored hazardous air pollutants (HAPs). Modeled annual ambient concentrations of HAPs in California came from the US Environmental Protection Agency’s National Air Toxics Assessment database for 1996, 1999, 2002, and 2005 and corresponding monitored data from the California Air Resources Board’s air quality monitoring program. We selected 12 compounds of interest for our study and focused on evaluating agreement between modeled and monitored data, and of temporal trends. Modeled data generally underestimated the monitored data, especially in 1996. For most compounds agreement between modeled and monitored concentrations improved over time. We concluded that 2002 and 2005 modeled data agree best with monitored data and are the most appropriate years for direct use in our subsequent epidemiologic analysis.     

Novel selective and metabolically stable inhibitors of anandamide cellular uptake

Novel aromatic analogues of N-oleoylethanolamine and N-arachidonoylethanolamine (anandamide, AEA) were synthesized and, based on the capability of similar compounds to interact with proteins of the endocannabinoid and endovanilloid signaling systems, were tested on: (i) cannabinoid CB(1) and CB(2) receptors; (ii) vanilloid VR1 receptors; (iii) anandamide cellular uptake (ACU); and (iv) the fatty acid amide hydrolase (FAAH). The (R)- and, particularly, the (S)-1'-(4-hydroxybenzyl) derivatives of N-oleoylethanolamine and AEA (OMDM-1, OMDM-2, OMDM-3, and OMDM-4) inhibited to a varied extent ACU in RBL-2H3 cells (K(i) ranging between 2.4 and 17.7 micro M), the oleoyl analogues (OMDM-1 and OMDM-2, K(i) 2.4 and 3.0 micro M, respectively) being 6- to 7-fold more potent than the arachidonoyl analogues (OMDM-3 and OMDM-4). These four compounds exhibited: (i) poor affinity for either CB(1) (K(i)> or = 5 micro M) or CB(2) (K(i)>10 micro M) receptors in rat brain and spleen membranes, respectively; (ii) almost no activity at vanilloid receptors in the intracellular calcium assay carried out with intact cells over-expressing the human VR1 (EC(50)> or = 10 micro M); and (iii) no activity as inhibitors of FAAH in N18TG2 cell membranes (K(i)>50 micro M). The oleoyl- and arachidonoyl-N'-(4-hydroxy-3-methoxybenzyl)hydrazines (OMDM-5 and OMDM-6), inhibited ACU (K(i) 4.8 and 7.0 micro M, respectively), and were more potent as VR1 agonists (EC(50) 75 and 50nM, respectively), weakly active as CB(1) receptor ligands (K(i) 4.9 and 3.2 micro M, respectively), and inactive as CB(2) ligands (K(i)>5 micro M) as well as on FAAH (K(i)> or = 40 micro M). In conclusion, we report two novel potent and selective inhibitors of ACU (OMDM-1 and OMDM-2) and one "hybrid" agonist of CB(1) and VR1 receptors (OMDM-6). Unlike other compounds of the same type, OMDM-1, OMDM-2, and OMDM-6 were very stable to enzymatic hydrolysis by rat brain homogenates.