Advances in Magnetic Resonance Imaging for the assessment of degenerative disc disease of the lumbar spine

The intervertebral disc is characterized by a tension-resisting annulus fibrosus, and a compression-resisting nucleus pulposus composed largely of proteoglycan. Both the annulus and the nucleus function in concert to provide the disc with mechanical stability. Early disc degeneration begins in the nucleus with proteoglycan depletion. Quantitative MRI techniques have been developed to non-invasively quantify the earliest degenerative changes that occur within the disc. Our ability to identify and quantify these early biochemical changes will provide a better understanding of the pathophysiology of disc degeneration and facilitate the study of interventions that aim to halt or reverse the degenerative process.     

Community survey of primary dystonia in the city of Kolkata, India.

An epidemiological study on dystonia has not been reported from India. As part of a major study to find out the prevalence of major neurological disorders in the large urban city of Kolkata, Eastern India, we planned to determine the prevalence of primary dystonia. The study design was a cross-sectional study of a sample population obtained through stratified random selection and conducted in a two-stage procedure of screening by a nonprofessional team followed by confirmation of screened positive cases by the study neurologist. A total population of 52,377 was screened, and 29 subjects with dystonia were diagnosed. Out of them 23 subjects had primary dystonias [crude prevalence rate (CPR), 43.91/100,000; 95% confidence interval (CI), 28.41-64.81; age-standardized rates to world standard population, 49.06 (95% CI,31.74-72.41)] and all cases were focal type and predominantly of limb dystonia variety. Mean onset of dystonias were earlier in women (43.5 years) as compared to men (46.6 years). Thus our study on primary dystonia shows higher prevalence when compared with that of many studies globally, predominantly of focal type, earlier onset among women, and more cases of limb dystonias when compared with more prominent blepharospasm and cervical dystonias in western reports.     

Extra- and intracellular free iron and the carotid body responses

The hypothesis that chelation of free iron, by decreasing reactive oxygen species (ROS), might mimic hypoxia and stimulate the carotid body was tested. We used the iron chelators, desferrioxamine (DFO, 200-400 microM) initially, and later ciclopirox olamine (CPX, 2.5-5.0 microM), on rat carotid body in vitro and measured chemosensory activity and [Ca2+]i in isolated cultured glomus cell clusters during normoxia and hypoxia. Although acute treatment of DFO might not penetrate the cell, and extracellular DFO would not influence these activities whereas CPX significantly increased chemosensory activities as well as increased [Ca2+]i in normoxia. We concluded that chelation of extracellular free iron did not alter ROS formation and oxygen sensing. Chelation of intracellular free iron and, therefore, a decrease in intracellular ROS appears to influence oxygen sensing in the carotid body.     

Phosphorus-Containing Fluoro-Sulfonated Polytriazole Membranes with High Proton Conductivity: Understanding Microstructural and Thermomechanical Behaviors as a Function of Degree of Sulfonation

The current article describes the design and synthesis of a new series of phosphorus-containing fluoro-sulfonated polytriazoles through click polymerization. The synthesized copolytriazoles (PTPFDSH-70 to 90) with different degrees of sulfonation (DS) from 70% to 90% are structurally interpreted by various spectroscopic techniques (¹H, ¹³C, and FTIR). The high molecular weight (weight average molecular weight as high as 77 500 g mol⁻¹ with polydispersity index of 2.29) polymers exhibits excellent mechanical (elongation at break up to 95%), thermal (10% decomposition temperature: 266–317 °C), and oxidative (>14.5 h) stability. The PTPFDSH-70 to 90 possess outstanding water-holding ability in hydrated conditions (swelling ratio [in-plane]: 6.2–7.3% at 80 °C). The microstructural alterations by their thermal relaxations and transitions with increasing DS in the polymers have been thoroughly investigated by dynamic mechanical analysis. The atomic force microscopy and transmission electron microscope images of the PTPFDSH-70 to 90 polymer membranes demonstrated the phase segregated interconnected ionic cluster-like morphology between hydrophilic and hydrophobic domains. The PTPFDSH-90 (DEB:PFAZ:DSAZ = 100:10:90) polymer membrane displays the proton conductivity (176 and 190 ms cm⁻¹ at 80 and 90 °C, respectively) higher than Nafion117 under similar test conditions.     

Anti-inflammatory effect of O-methylated flavonol 2-(3,4-dihydroxy-phenyl)-3,5-dihydroxy-7-methoxy-chromen-4-one obtained from Cassia sophera Linn in rats

Ethnopharmacological relevance

Cassia sophera Linn (Family Caesalpiniaceae), popularly known as kasundi, is used both in the Indian traditional system and folk medicine to treat several inflammatory pathologies such as asthma, arthritis and pains. The aim of the present study was to evaluate the scientific basis of anti-inflammatory activity of Cassia sophera ethanol extracts and of an isolated constituent of Cassia sophera.

Materials and methods

The anti-inflammatory activity of Cassia sophera was studied using the carrageenan, dextran induced rat paw edema, and cotton pellet induced granuloma in rats. The ethanol extract was administered at the concentrations of 200 and 400 mg/kg body weight whereas rhamnetin (RN) was administered at a dose of 10 and 15 mg/kg, b.w. Indomethacin was used as standard drug.

Results

The HPLC analysis revealed that good amounts of rhamnetin (0.18%) was present in Cassia sophera.The ethanol extracts at 400 mg/kg, showed maximum inhibition of inflammation induced by carrageenan (44%), dextran (40%), cotton pellets (37.47%). On the other hand rhamnetin (15 mg/kg) exhibited maximum anti-inflammatory effect, that is 79 and 33% at the end of 3 h with carrageenin, and dextran-induced rat paw edema, respectively. In a chronic test rhamnetin (15 mg/kg) showed 43.32% reduction in granuloma weight.

Conclusion

The marked inhibitory effect on paw edema and granuloma showed that Cassia sophera possess remarkable anti-inflammatory activity which may be due to rhamnetin at least in part, supporting the folkloric usage of the plant to treat various inflammatory diseases.     

A novel N-hydroxy-N′-aminoguanidine derivative inhibits ribonucleotide reductase activity: Effects in human HL-60 promyelocytic leukemia cells and synergism with arabinofuranosylcytosine (Ara-C)

Ribonucleotide reductase (RR; EC 1.17.4.1) is responsible for the de novo conversion of ribonucleoside diphosphates into deoxyribonucleoside diphosphates, which are essential for DNA replication. RR is upregulated in tumor cells and therefore considered to be an excellent target for cancer chemotherapy.ABNM-13 (N-hydroxy-2-(anthracene-2-yl-methylene)-hydrazinecarboximidamide), a novel N-hydroxy-N′-aminoguanidine has been designed to inhibit RR activity using 3D molecular space modeling techniques. In this study, we evaluated its effect on human HL-60 promyelocytic leukemia cells. ABNM-13 proved to be a potent inhibitor of RR which was displayed by significant alterations of deoxyribonucleoside triphosphate (dNTP) pool balance and a highly significant decrease of incorporation of radiolabeled cytidine into DNA of HL-60 cells. Diminished RR activity caused replication stress which was consistent with activation of Chk1 and Chk2, resulting in downregulation/degradation of Cdc25A. In contrast, Cdc25B was upregulated, leading to dephosphorylation and activation of Cdk1. The combined disregulation of Cdc25A and Cdc25B was the most likely cause for ABNM-13 induced S-phase arrest. Finally, we combined ABNM-13 with the first-line antileukemic agent arabinofuranosylcytosine (Ara-C) and found that ABNM-13 synergistically potentiated the antineoplastic effects of Ara-C.Due to these promising results, ABNM-13 deserves further preclinical and in vivo testing.