Impact of metal accumulation pattern on the annual rhythmicity of antioxidants and their interrelationship to maintain the oxidative balance in mollusc

A chronological relationship between the annual profiles of oxidative stress markers, the key regulator of stress physiology has been sought in a terrestrial mollusc (Nerita articulata) under natural photothermal conditions. The hemolymph samples were collected at two different times in each month (from January to December) and the same was repeated for two consecutive years throughout an annual cycle. The fluctuations in the concentrations of certain heavy and trace metals (zinc, copper, cadmium, mercury, lead, and nickel) in both soil and hemolymph of Nerita are also estimated accordingly. Therefore, the present study aims to explore the rhythmic responses of oxidative stress marker to assess the impact of different trace and heavy metals on selected mollusc species. We tries to develop a realistic conceptual idea to analyze and predict the effect of changing environmental pollution on the possible shift in the rhythmicity of aforesaid antioxidants in terrestrial mollusc and their adaptive responses to thrive in such environment. Our results indicates that the amplitude of circannual rhythms of all the selected stress markers varied accordingly but the pattern of annual fluctuation is noted to be similar, and correlated with the metal accumulation. Therefore current information might help to frame the adaptive strategies for invertebrate species under similar toxic circumstances.     

Increased aortic intima-media thickness is related to lipid profile in newborns with intrauterine growth restriction

BACKGROUND AND AIM: Low birth-weight is known to be associated with an increase in cardiovascular risk similar to that seen with major environmental risk factors, such as cigarette smoking or hypertension. Much epidemiological evidence has linked low birth-weight with hypertriglyceridaemia. METHOD: We measured aortic wall thickness by ultrasonography and lipid profile in 40 newborn babies with intrauterine growth restriction and 40 controls. RESULTS: Maximum and mean aortic intima-media thickness were significantly higher in the babies with intrauterine growth retardation (0.58 +/- 0.06, 0.52 +/- 0.03 mm, respectively) than in controls (0.44 +/- 0.05, 0.40 +/- 0.03 mm, p < 0.0001, p < 0.0001, respectively), more so after adjustment for birth-weight (maximum intima-media thickness: 0.23 +/- 0.03 mm/kg vs. 0.12 +/- 0.02 mm/kg, p < 0.0001; mean intima-media thickness: 0.21 +/- 0.02 mm/kg vs. 0.11 +/- 0.01 mm/kg, p < 0.0001). Serum triglyceride levels were significantly higher in the intrauterine growth retardation group (48.9 +/- 14.8 mg/dl) compared with the control group (32.5 +/- 9.8 mg/dl, p < 0.0001). The mean body mass index, prepregnancy weight, weight gain during pregnancy, maternal LDL cholesterol level and, height of the mothers were significantly lower in the intrauterine growth retardation group compared with the control group. For maximum aIMT, significant associations included the ponderal index (p = <0.01), length (p = 0.01) and serum triglyceride levels of infants (p = 0.02). CONCLUSION: Newborn babies with growth restriction have significant maximum aortic thickening with hypertriglyceridaemia, suggesting that prenatal events might predispose to later cardiovascular risk.     

Paraoxonase and arylesterase levels in autoimmune thyroid diseases

Objective: The aim of this study was to evaluate serum paraoxonase-1 (PON1) activity and its association with oxidative stress in autoimmune thyroid disease (AITD).

Methods: A total of 50 patients with AITD, including 25 with Hashimoto's thyroiditis and 25 with Graves’ disease were enrolled. The control group comprised 27 healthy subjects. Blood samples were obtained in the euthyroid period and 3 months after initiation of medical treatment. Serum samples from patients with AITD and the healthy control group were analyzed for basal PON1, salt-stimulated PON1, and arylesterase (ARE) activities, along with lipid hydroperoxide (LOOH) and total free sulfhydryl (–SH) levels.

Results: Serum PON1 activities and –SH levels were significantly lower (P?<?0.001, for each), whereas LOOH levels were significantly higher (P?<?0.001, for each) in patients with AITD, compared to the control group. We observed no significant differences in ARE levels between the patient and healthy control groups (P?>?0.05). PON1 activity was positively correlated with –SH (r?=?0.522, P?<?0.001) and negatively correlated with LOOH (r?=??0.487, P?<?0.001). PON1 phenotype distribution of the subjects was not significantly different among the three groups (P?=?0.961).

Conclusions: Serum PON1 activity is decreased in patients with AITD, and correlated positively with –SH, a well-known antioxidant, and negatively with LOOH, an index of lipid oxidation.     

Synthesis and carbonic anhydrase inhibitory properties of novel bromophenols including natural products

(2-Bromo-3,4-dimethoxyphenyl) (3,4-dimethoxyphenyl)methanone (10) and its derivatives with Br, one dibromide and isomeric three tribromides, were synthesized. Demethylation of these compounds afforded a series of new bromophenols. Inhibition of human cytosolic carbonic anhydrase II (hCA II) isozyme by these new bromophenols and naturally occurring 3,4,6-tribromo-5-(2,5-dibromo-3,4-dihydroxybenzyl)benzene-1,2-diol (3), and 5,5'-methylenebis(3,4,6-tribromo-benzene-1,2-diol) (4) was investigated. The synthesized compounds showed carbonic anhydrase inhibitory capacities with IC(50) values in the range of 0.7-372 μM against hCA II. Some bromophenols investigated here showed effective hCA II inhibitory activity and might be used as leads for generating novel carbonic anhydrase inhibitors which are valuable drug candidates for the treatment of glaucoma, epilepsy, gastric and duodenal ulcers, neurological disorders, or osteoporosis.     

Replication and discrimination of limb movement velocity

It is well known that proprioception is composed of the senses of movement and position. Whereas tests of position sense are quite commonly used, tests of the acuity in perception of movement velocity are scarce. In the present study we examined some novel tests for assessing the sense of limb movement velocity, involving replication and discrimination of single-joint movement velocity. Specifically, we investigated: (1) whether replication of limb movement velocity is more accurate following active criterion movements as compared to passive; (2) whether antagonist muscle contraction during passive limb movement enhances velocity discrimination; (3) how criterion movement velocity influences response accuracy; (4) the relationship between movement velocity and movement extent during velocity replication; and (5) whether subjects really base discrimination of velocities on perceived velocity. Sixteen healthy subjects participated in four tests (I-IV). For each test, horizontal abductions were performed about the right glenohumeral joint from the sagittal plane. The subjects were required to actively replicate the velocity of either an active (Test I) or passive (Test II) criterion movement, or judge whether a passive/semipassive (passive during antagonist muscle contraction) movement was faster or slower than a previous passive/semipassive criterion movement (Test III/IV). The results revealed higher response accuracy for Test I compared to Test II and for slower movements compared to faster, but no difference in response accuracy between Test III and IV. For velocity discrimination, the analysis revealed that the subjects based their judgment on the difference between criterion and comparison velocity rather than time or extent cues.     

Structural and inhibition analysis of novel sulfur-rich 2-mercaptobenzothiazole and 1,2,3-triazole ligands against <Emphasis Type="Italic">Mycobacterium tuberculosis</Emphasis> DprE1 enzyme

Mycobacterium tuberculosis decaprenylphosphoryl-β-d-ribose oxidase (MtbDprE1) acts in concert with decaprenylphosphoryl-β-d-ribose 2-epimerase (MtbDprE2) and catalyzes the epimerization of DPR into DPA. DPA is the sole precursor for synthesis of arabinogalactan and lipoarabinomannan in the mycobacterial cell wall. MtbDprE1 is a unique antimalarial drug target and many covalent and non-covalent inhibitors against MtbDprE1 have been studied for their antituberculosis activities. In the current study, we have purified MtbDprE1 enzyme and synthesized six sulfur-rich 2-mercaptobenzothiazole and 1, 2, 3-triazole conjugated ligands and performed binding analysis with MtbDprE1. All ligands have shown competitive binding, as observed for other covalently and noncovalently bound MtbDprE1 inhibitors. Molecular docking analysis of six ligands with MtbDprE1 shows that they occupy the substrate binding pocket of MtbDprE1 and are stabilized by hydrogen bonds and van der Waals interactions. Our study shows that sulfur-rich 2-mercaptobenzothiazole ligands act as specific inhibitors against MtbDprE1 and could be used as antituberculosis agents.     

The Germinal Center Kinase TNIK Is Required for Canonical NF-κB and JNK Signaling in B-Cells by the EBV Oncoprotein LMP1 and the CD40 Receptor

The tumor necrosis factor-receptor-associated factor 2 (TRAF2)- and Nck-interacting kinase (TNIK) is a ubiquitously expressed member of the germinal center kinase family. The TNIK functions in hematopoietic cells and the role of TNIK-TRAF interaction remain largely unknown. By functional proteomics we identified TNIK as interaction partner of the latent membrane protein 1 (LMP1) signalosome in primary human B-cells infected with the Epstein-Barr tumor virus (EBV). RNAi-mediated knockdown proved a critical role for TNIK in canonical NF-κB and c-Jun N-terminal kinase (JNK) activation by the major EBV oncoprotein LMP1 and its cellular counterpart, the B-cell co-stimulatory receptor CD40. Accordingly, TNIK is mandatory for proliferation and survival of EBV-transformed B-cells. TNIK forms an activation-induced complex with the critical signaling mediators TRAF6, TAK1/TAB2, and IKKβ, and mediates signalosome formation at LMP1. TNIK directly binds TRAF6, which bridges TNIK's interaction with the C-terminus of LMP1. Separate TNIK domains are involved in NF-κB and JNK signaling, the N-terminal TNIK kinase domain being essential for IKKβ/NF-κB and the C-terminus for JNK activation. We therefore suggest that TNIK orchestrates the bifurcation of both pathways at the level of the TRAF6-TAK1/TAB2-IKK complex. Our data establish TNIK as a novel key player in TRAF6-dependent JNK and NF-κB signaling and a transducer of activating and transforming signals in human B-cells.     

Antioxidant and Antimicrobial Activity in Some Indian Herbal Plants: Protective Effect against Free Radical Mediated DNA Damage

Indian herbal plant species Lantana indica, Adhatoda vasica, Pandanus furcatus, Tylophora indica and Centella asiatica, traditionally used in ethno medicines to treat common infections and various disorders, have been studied for their antimicrobial and antioxidant activity. The methanolic extracts of the plant leaves exhibited significant and dose-dependent antioxidant activities in DPPH radical scavenging, ferric ion reducing and phosphomolybdate assays. These leaf extracts showed antimicrobial activity against selected Gram +ve and Gram ?ve bacterial strains. A. vasica and L. indica extracts possessed maximum antioxidant and antimicrobial activity, respectively. The activities could be correlated to phenolics and flavonoid content of the leaf extracts which ranged from 30.25 to 91.98 mg GAE g^?1 dw leaf extract and 2.67 to 96.45 mg RE g^?1 dw leaf extract respectively. The aqueous extracts of plant leaves significantly protected the DNA damage against the oxidative damage caused by hydroxyl radicals.     

Synthesis and potent antimicrobial activity of some novel methyl or ethyl 1H-benzimidazole-5-carboxylates derivatives carrying amide or amidine groups

A series of benzimidazole-5-carboxylic acid alkyl ester derivatives carrying amide or amidine substituted methyl or phenyl groups at the position C-2 were synthesised and evaluated for antibacterial and antifungal activities against S. aureus, methicillin resistant S. aureus (MRSA), S. faecalis, methicillin resistant S. epidermidis (MRSE), E. coli and C. albicans. The results showed that while all simple acetamides are essentially inactive, aromatic amides and amidines have potent antibacterial activities. Aromatic amidine derivatives 13 f-h exhibited the best inhibitory activity with 1.56-0.39 microg/mL MIC values against MRSA and MRSE.