Effects of long‐term inhibition of neuronal nitric oxide synthase on blood pressure and renin release

Nitric oxide (NO) produced by neuronal NO‐synthase (nNOS) in macula densa cells may be involved in the control of renin release. 7‐Nitro indazole (7‐NI) inhibits nNOS, and we investigated the effect of short‐ (4 days) and long‐term (4 weeks) 7‐NI treatment on blood pressure (BP), plasma renin concentration (PRC) and glomerular filtration rate (GFR) in rats on different salt diets. Rats were divided into three groups and given low‐salt (LS), normal (C) and high‐salt (HS) diets. Each diet group was subdivided into two groups treated either with 7‐NI or vehicle. Long‐term 7‐NI‐treated rats (LS and C) showed increased BP compared with controls (LS: 149 ± 4 vs. 133 ± 3; C: 146 ± 4 vs. 127 ± 4 mmHg). Blood pressure in HS rats did not differ from that in controls. Plasma renin concentration was stimulated in LS‐rats (251 ± 64 mGU mL^–1) compared with C and HS rats (42 ± 8 and 39 ± 5 mGU mL^–1, respectively) but was not significantly affected by chronic 7‐NI treatment (350 ± 103, 49 ± 10 and 50 ± 15 mGU mL^–1 in LS, C and HS, respectively). In rats treated with 7‐NI for 4 days, no effect on BP was seen, but PRC was increased in 7‐NI treated LS rats compared with vehicle treated LS rats (107 ± 15 vs. 56 ± 1 mGU mL^–1). Stimulation of PRC in LS rats was further enhanced by 7‐NI after 4 days of treatment, but not affected in rats treated for 4 weeks. This suggests that inhibition of nNOS stimulates renin release but that this stimulatory effect in the long run might be depressed by the increase in blood pressure.     

Mutagenicity profile of atmospheric particulate matter in a small urban center subjected to airborne emission from vehicle traffic and sugar cane burning

Atmospheric particulate matter (PM) is genotoxic and recently was classified as carcinogenic to humans by the International Agency for Research on Cancer. PM chemical composition varies depending on source and atmospheric conditions. The Salmonella/microsome assay is the most used mutagenicity test and can identify the major chemical classes responsible for observed mutagenicity. The objective of this work was to characterize the mutagenicity of PM samples from a countryside city, Limeira, Brazil, which is influenced by heavy traffic and sugar cane biomass burning. Six samples of total PM were collected. Air mass backward trajectories were calculated. Organic extracts were assayed using the Salmonella/microsome microsuspension mutagenicity assay using TA98, YG1041, and TA1538, with and without metabolic activation (S9). YG1041 was the most sensitive strain and mutagenicity reached 9,700 revertants per m³ without metabolic activation. Potency for TA1538 was higher than TA98, indicating that this strain should be considered in air mutagenicity studies. The increased response to YG1041 relative to TA98, and the decreased response with S9, suggests that nitroaromatics are the major contributors. Limeira is among the most mutagenic cities in the world. High mutagenicity in Limeira seems to occur when the air mass from the area of sugarcane production is mixed with air from the region impacted by anthropogenic activities such as traffic. An increase in the formation of nitro‐polycyclic aromatic hydrocarbons may result from longer contact time between the aromatic compounds and the atmosphere with high NOx and ozone concentration, although more studies are required to confirm this hypothesis. Environ. Mol. Mutagen. 57:41–50, 2016. © 2015 Wiley Periodicals, Inc.     

Arylnitro monocarbonyl curcumin analogues: Synthesis and in vitro antitubercular evaluation

Curcumin is a natural product that has been reported to exhibit myriad pharmacological properties, one of which is antitubercular activity. It demonstrates antitubercular activity by directly inhibiting Mycobacterium tuberculosis (M.tb) and also enhances immune responses that ultimately lead to the elimination of M.tb by macrophages. This natural product is, however, unstable, and several analogues, noticeably monocarbonyl analogues, have been synthesized to overcome this challenge. Curcumin and its monocarbonyl analogues reported so far exhibit moderate antitubercular activity in the range of 7 to 16 μM. Herein, we report a straightforward synthesis of novel monocarbonyl curcumin analogues, their antitubercular activity, and the structure–activity relationship. The hit compound from this study, 3a , exhibits potent MIC₉₀ values in the range of 0.2 to 0.9 μM in both ADC and CAS media.     

The regulatory and modulatory roles of TRP family channels in malignant tumors and relevant therapeutic strategies

Transient receptor potential (TRP) channels are one primary type of calcium (Ca²⁺) permeable channels, and those relevant transmembrane and intracellular TRP channels were previously thought to be mainly associated with the regulation of cardiovascular and neuronal systems. Nowadays, however, accumulating evidence shows that those TRP channels are also responsible for tumorigenesis and progression, inducing tumor invasion and metastasis. However, the overall underlying mechanisms and possible signaling transduction pathways that TRP channels in malignant tumors might still remain elusive. Therefore, in this review, we focus on the linkage between TRP channels and the significant characteristics of tumors such as multi-drug resistance (MDR), metastasis, apoptosis, proliferation, immune surveillance evasion, and the alterations of relevant tumor micro-environment. Moreover, we also have discussed the expression of relevant TRP channels in various forms of cancer and the relevant inhibitors’ efficacy. The chemo-sensitivity of the anti-cancer drugs of various acting mechanisms and the potential clinical applications are also presented. Furthermore, it would be enlightening to provide possible novel therapeutic approaches to counteract malignant tumors regarding the intervention of calcium channels of this type.