<Emphasis Type="Italic">Chenopodium</Emphasis>: a prospective plant for phytoextraction

Leaf samples were collected from 40 accessions of Chenopodium spp. and assessed for six heavy metals (Fe, Zn, Cu, Ni, Cr and Cd) accumulation to explore the use of Chenopodium for phytoextraction of heavy metals. The results suggest that Chenopodium spp. have the ability to accumulate large quantities of heavy metals in the leaf tissues even when they are present in low concentrations in the soil. C. quinoa is a better accumulator of Ni, Cr and Cd than the rest of the species, while C. album accessions are good copper accumulators. Bioconcentration factor for chromium ranged from 0.36 (C. album “Chandanbathua”) to 6.57 (C. quinoa Ames 13719) with 13 accessions of C. quinoa scoring above the mean value. High heritability coupled with high genetic advance was recorded for Ni, Cr and Cd, which indicated a major role of additive gene action in the inheritance of these characters. Zinc showed significant positive association with iron (0.351**), nickel (0.659**), chromium (0.743**) and cadmium (0.288**). Nickel was significantly and negatively associated with copper (−0.663**), while it was positively and significantly correlated with chromium (0.682**) and cadmium (0.461**). Considering the accumulation efficiency of Chenopodium spp. with respect to heavy metals, this genus should be further explored for decontamination of metal polluted soils, with plant breeding playing an important role in evolving new plant types with higher capacity of heavy metal accumulation.     

The anergic state in sarcoidosis is associated with diminished dendritic cell function

Sarcoidosis is a chronic inflammatory disease of unknown cause, characterized by granuloma formation similar to tuberculosis, but without clear evidence of a microbial infection. Because sarcoidosis is linked with clinical anergy and other evidence of diminished cellular immunity, we hypothesized that decreased skin delayed-type hypersensitivity (DTH) responses to recall Ags in affected individuals would be associated with decreased function of their blood dendritic cells (DCs). Our study involved ex vivo isolation, phenotyping, and functional testing of myeloid DCs (mDCs), plasmacytoid DCs, and T lymphocytes from blood of normal healthy volunteers and sarcoidosis subjects with active, untreated pulmonary disease. We found mDC function in the allogeneic MLR directly corresponded to the magnitude of skin DTH reactions to recall Ags in both sarcoidosis subjects and normal volunteers. However, both of these outcomes were significantly decreased in the sarcoidosis group. Diminished mDC function occurred despite up-regulated costimulatory and maturation markers. Clinical relevance is suggested by the inverse relationship between both mDC allogeneic responses and skin DTH responses with clinical disease severity as measured by chest radiograms. Because granulomas form when cellular immunity fails to clear antigenic stimuli, attenuated mDC function in sarcoidosis may contribute to susceptibility and persistence of the chronic inflammation characteristic of this disease.     

Effects of 28-homobrassinolide on nickel uptake,protein content and antioxidative defence system in <Emphasis Type="Italic">Brassica juncea</Emphasis>

The effects of 28-homobrassinolide (HBL) on nickel uptake, protein content and activities of antioxidative enzymes were determined in the seedlings of Brassica juncea L. The seeds were treated with different concentrations (0, 0.01, 1 and 100 nM) of HBL for 8 h and then sown in the Petri plates containing various concentrations (0, 25, 50 and 100 mg dm⁻³) of nickel. After 7 d, observations were made on shoot and root length, Ni uptake, protein content and activities of antioxidative enzymes (guaiacol peroxidase, catalase, glutathione reductase, ascorbate peroxidase and superoxide dismutase). The growth of seedlings was inhibited by Ni, however, less after HBL pre-treatment. The protein content and antioxidative enzyme activities were also increased by HBL treatment.     

ACE I/D polymorphism in Indian patients with hypertrophic cardiomyopathy and dilated cardiomyopathy

Aim The study was carried to determine the association of angiotensin converting enzyme (ACE) insertion/deletion (I/D) polymorphism with the risk of hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and restrictive cardiomyopathy (RCM). Methods and results A total of 174 patients diagnosed with cardiomyopathy (118 with HCM, 51 with DCM, and 5 with RCM) and 164 ethnically, age- and gender-matched controls were included in the study. ACE I/D genotyping was performed by PCR. In total, 25.86% of the patients were in New York Heart Association (NYHA) class III and IV at presentation. A total of 67.24% patients had dyspnea, 56.89% had angina pectoris, and 25.28% of the patients had at least one event of syncope. Frequency of occurrence of the disease was more in male patients compared to female patients (P < 0.05). After adjustment for age, sex, body mass index (BMI), and smoking habit, the prevalence of ACE DD genotype, and ACE ‘D’ allele was significantly higher in patients as compared to controls and was associated with increased risk (DD: OR 2.11, 95% CI 1.27–3.52, P < 0.05; ‘D’: OR 1.91, 95% CI 1.08–3.35, P < 0.05). The mean septal thickness was higher for DD and ID genotypes (20.40 ± 3.73 mm and 21.82 ± 5.35 mm, respectively) when compared with II genotype (18.63 ± 6.69 mm) in HCM patients, however, the differences were not significant statistically (P > 0.05). The DCM patients with ID genotype showed significantly decreased left ventricular ejection fraction (LVEF) at enrolment (26.50 ± 8.04%) (P = 0.04). Conclusion Our results suggest that D allele of ACE I/D polymorphism significantly influences the HCM and DCM phenotypes.     

Tethering and tickling: a new role for the phosphatidylserine receptor

Several receptors are implicated in apoptotic cell (AC) uptake by phagocytic cells; however, their relative dominance in mammalian systems remains to be established. New studies shed light on the role of the phosphatidyl serine (PS) receptor (PSR). Ligation of PSR by PS on AC surfaces is considered essential for signaling uptake of ACs that are tethered to phagocytes via other receptors.     

Rapid synthesis of 4-benzylidene and 4-[bis-(4-methoxyphenyl)-methylene-2-substituted phenyl-benzopyrans as potential selective estrogen receptor modulators (SERMs) using McMurry coupling reaction

7-Methoxy-4-(4-methoxybenzylidene)-2-substituted phenyl-benzopyrans I and 4-[bis-(4-methoxyphenyl)-methylene-2-substituted phenyl-benzopyrans II carrying different alkylamino residues, designed as estrogen receptor (ER) binding ligands, were successfully synthesized through the McMurry coupling reaction of substituted benzaldehyde/substituted benzophenones and 2-hydroxyphenyl-7-methoxy-chroman-4-one in presence of lithium aluminum hydride and titanium (IV) chloride (LAH-TiCl(4)). Self-coupling of carbonyl reactants led to the formation of several side products. The prototypes were evaluated for their relative binding affinity (RBA), as well as their estrogenic and antiestrogenic activities. High order of estrogenic activity (>50% gain) observed with compounds 3, 7a, 7b, 7c, 8, and 10a and also their partial estrogen antagonistic activity (> or =15%) at the uterine level points toward successful designing of the compounds. Compounds 4, 7a, 7b, 7c, and 10a also possessed significant anticancer activity against human adenocarcinoma cell line (MCF-7 cell line) that may be related to their estrogen-dependent action.     

Biomarkers of oxidative damage to predict ischaemia-reperfusion injury in an isolated organ perfusion model of the transplanted kidney

Ischaemia-reperfusion (IR) injury is known to be a risk factor influencing both short and long-term graft function following transplantation. The pathophysiology of IR injury is suggested to involve elevated reactive oxygen species production resulting in oxidative damaged cellular macromolecules. The objective of this study was to evaluate oxidative damage following IR using an isolated organ perfusion model of the transplanted kidney, in order to determine a simple, preferably non-invasive biomarker for IR injury. Porcine kidneys were retrieved with 10 or 40 min warm ischaemic (WI) time and haemoperfused for 6 h on an isolated organ perfusion machine. ELISA was used to detect carbonyls, 8-isporostane and 8-hydroxy-2'-deoxyguanosine, representing protein, lipid and DNA damage respectively in pre and post reperfusion samples of plasma, urine and biopsy material. Plasma carbonyl and 8-isporostane and were significantly increased in the 40 min group compared to pre-perfusion (0.96 +/- 0.10 vs. 0.62 +/- 0.06, P < 0.001 and 1.57(1.28-4.9) vs. 0.36(0.09-0.59), P < 0.05). The levels also correlated with creatinine clearance used to determine renal function (r = - 0.6150, P < 0.01 and r = - 0.7727, P < 0.01). The results of this study suggest both plasma carbonyl and 8-isporostane to be reliable biomarkers to predict the level IR injury.     

An overview on 5α-reductase inhibitors

Benign prostatic hyperplasia (BPH) is the noncancerous proliferation of the prostate gland associated with benign prostatic obstruction and lower urinary tract symptoms (LUTS) such as frequency, hesitancy, urgency, etc. Its prevalence increases with age affecting around 70% by the age of 70 years. High activity of 5α-reductase enzyme in humans results in excessive dihydrotestosterone levels in peripheral tissues and hence suppression of androgen action by 5α-reductase inhibitors is a logical treatment for BPH as they inhibit the conversion of testosterone to dihydrotestosterone. Finasteride (13) was the first steroidal 5α-reductase inhibitor approved by U.S. Food and Drug Administration (USFDA). In human it decreases the prostatic DHT level by 70-90% and reduces the prostatic size. Dutasteride (27) another related analogue has been approved in 2002. Unlike Finasteride, Dutasteride is a competitive inhibitor of both 5α-reductase type I and type II isozymes, reduced DHT levels >90% following 1 year of oral administration. A number of classes of non-steroidal inhibitors of 5α-reductase have also been synthesized generally by removing one or more rings from the azasteroidal structure or by an early non-steroidal lead (ONO-3805) (261). In this review all categories of inhibitors of 5α-reductase have been covered.     

Self-organizing molecular field analysis on pregnane derivatives as human steroidal 5α-reductase inhibitors

Normal growth and development of human prostate is regulated by the androgens which balances cell proliferation and apoptosis. Testosterone (T) and dihydrotestosterone (DHT) are the two key androgens that stimulate most of the androgen action in prostate. Testosterone is converted to DHT by the membrane bound NADPH-dependent 5α-reductase enzyme. As a consequence of the important observation that progesterone and deoxycortisone inhibits the synthesis of DHT by competing with 4-en-3-one function of the testosterone for the 5α-reductase enzyme a number of pregnane derivatives were synthesized and have been reported as inhibitors of human 5α-reductase enzyme. Due to lack of information on the crystal structure of human 5α-reductase, ligand-based 3D-QSAR study has been performed on pregnane derivatives using self-organizing molecular field analysis (SOMFA) for rationalizing the molecular properties and human 5α-reductase inhibitory activities. The statistical results having good cross-validated (0.881), non-cross-validated r² (0.893) and F-test value (175.527), showed satisfied predictive ability (0.777). Analysis of SOMFA models through electrostatic and shape grids provide useful information for the design and optimization of steroidal structure as novel human 5α-reductase inhibitors.