T1 assessment of hip joint cartilage following intra‐articular gadolinium injection: A pilot study

This pilot study defines the feasibility of cartilage assessment in symptomatic femoroacetabular impingement patients using intra‐articular delayed gadolinium‐enhanced MRI of cartilage (ia‐dGEMRIC). Nine patients were scanned preliminary to study the contrast infiltration process into hip joint cartilage. Twenty‐seven patients with symptomatic femoroacetabular impingement were subsequently scanned with intra‐articular delayed gadolinium‐enhanced MRI of cartilage. These T₁ findings were correlated to morphological findings. Zonal variations were studied. This pilot study demonstrates a significant difference between the pre‐ and postcontrast T₁ values (P < 0.001) remaining constant for 45 min. We noted higher mean T₁ values in morphologically normal‐appearing cartilage than in damaged cartilage, which was statistically significant for all zones except the anterior‐superior zone. Intraobserver (0.972) and interobserver correlation coefficients (0.933) were statistically significant. This study outlines the feasibility of intra‐articular delayed gadolinium‐enhanced MRI of cartilage for assessment of cartilage changes in patients with femoroacetabular impingement. It can also define the topographic extent and differing severities of cartilage damage. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

DNA-Binding Interaction Studies of Microwave Assisted Synthesized Sulfonamide Substituted 8-Hydroxyquinoline Derivatives

Sulfonamide substituted 8-hydroxyquinoline derivatives were prepared using a microwave synthesizer. The interaction of sulfonamide substituted 8-hydroxyquinoline derivatives and their transition metal complexes with Plasmid (pUC 19) DNA and Calf Thymus DNA were investigated by UV spectroscopic studies and gel electrophoresis measurements. The interaction between ligand/metal complexes and DNA was carried out by increasing the concentration of DNA from 0 to 12 μl in UV spectroscopic study, while the concentration of DNA in gel electrophoresis remained constant at 10 μl. These studies supported the fact that, the complex binds to DNA by intercalation via ligand into the base pairs of DNA. The relative binding efficacy of the complexes to DNA was much higher than the binding efficacy of ligands, especially the complex of Cu-AHQMBSH had the highest binding ability to DNA. The mobility of the bands decreased as the concentration of the complex was increased, indicating that there was increase in the interaction between the metal ion and DNA. Complexes of AHQMBSH were excellent for DNA binding as compared to HQMABS.     

Case series of neonatal hypocalcemia due to pseudohypoparathyroidism

Four children; all between 10-40 days of age, were admitted with multiple episodes of multifocal seizure. After admission blood investigation was carried out and they were found to have hypocalcemia, hyperphosphatemia; kidney function tests were normal. Serum parathyroid hormone was highly elevated and serum magnesium level was found to be normal in these patients. The infants did not have any other features of pseudohypoparathyroidism. The seizure was initially resistant to intravenous calcium therapy and later responded to oral calcitriol and calcium therapy. The diagnosis of pseudohypoparathyroidism was made according to biochemical investigations. The infants were symptom-free during follow-up and the biochemistry reports were also normalized. One of the infants was also suffering from neonatal hepatitis, due to CMV infection.     

4‐Hydroxy‐α‐Tetralone and its Derivative as Drug Resistance Reversal Agents in Multi Drug Resistant Escherichia coli

The purpose of present investigation was to understand the drug resistance reversal mechanism of 4‐hydroxy‐α‐tetralone ( 1 ) isolated from Ammannia spp. along with its semi‐synthetic derivatives ( 1a – 1e ) using multidrug resistant Escherichia coli (MDREC). The test compounds did not show significant antibacterial activity of their own, but in combination, they reduced the minimum inhibitory concentration (MIC) of tetracycline (TET). In time kill assay, compound 1 and its derivative 1e in combination with TET reduced the cell viability in concentration dependent manner. Compounds 1 and 1e were also able to reduce the mutation prevention concentration of TET. Both compounds showed inhibition of ATP dependent efflux pumps. In real time polymerase chain reaction (RT‐PCR) study, compounds 1 and 1e alone and in combination with TET showed significant down expression of efflux pump gene (yojI) encoding multidrug ATP binding cassettes (ABC) transporter protein. Molecular mechanism was also supported by the in silico docking studies, which revealed significant binding affinity of compounds 1 and 1e with YojI. This study confirms that compound 1 and its derivative 1e are ABC efflux pump inhibitors which may be the basis for development of antibacterial combinations for the management of MDR infections from inexpensive natural product.     

Effects of cadmium(II) on (+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide-induced DNA damage response in human fibroblasts and DNA repair: a possible mechanism of cadmium's cogenotoxicity

Cadmium, a widespread environmental pollutant and a cigarette smoke constituent, enhances the genotoxicity of benzo[a]pyrene (BP). The mechanism(s) underlying the potentiation of BP-induced genotoxicity by Cd2+ is not clearly understood. Our studies of the effects of noncytotoxic concentrations of Cd2+ on the levels of p53 and p21 in (+/-)-anti-benzo[a]pyrene-7,8-diol-9,10-epoxide (BPDE)-treated human fibroblasts showed that Cd2+ decreased BPDE-induced p21 levels in a dose-dependent manner whereas p53 accumulation is attenuated only at higher noncytotoxic concentrations of cadmium. These findings suggest that both the activity and the accumulation of p53 in response of BPDE treatment are inhibited by Cd2+ although the possibility of p53-independent p21 transactivation cannot be ruled out. Exposure of synchronized human fibroblast cells to 0.5 microM of BPDE caused 72% of the cells remaining in G1 phase as compared to 52% in the case of untreated cells. Treatment of the cells with CdCl2 prior to exposing them to BPDE caused a decrease in the G1 population (72 to 54%) in a dose-dependent manner. An in vitro repair assay of BPDE-damaged pUC18 plasmid DNA using untreated and cadmium-treated nucleotide excision repair (NER) proficient HeLa extract showed that cadmium impaired the ability of HeLa cell extract to repair BPDE-damaged pUC18 DNA. Our findings indicate that cadmium not only inhibits NER pathway-dependent repair of BPDE-damaged DNA but also impairs p53 and p21 responses and overrides BPDE-induced G1-S cell cycle arrest. The effect of cadmium on these processes may explain, at least partly, the potentiating effect of the metal on the genotoxicity of BP.     

Enhancement of paclitaxel-induced microtubule stabilization, mitotic arrest, and apoptosis by the microtubule-targeting agent EM012

EM012, a semisynthetic phthalideisoquinoline alkaloid, has been recently found to target microtubules and possess anti-cancer activity. In this study, we evaluated the effects of EM012 in combination with the classic microtubule-targeting agent paclitaxel. Our results demonstrated that EM012 enhanced the anti-proliferative activity of nanomolar concentrations of paclitaxel in human breast cancer (MCF7), prostate cancer (DU145), and non-small-cell lung cancer (A549) cells. Further studies revealed that EM012 increased the ability of nanomolar concentrations of paclitaxel to induce mitotic arrest and apoptosis, without affecting microtubule polymerization. In contrast, when micromolar concentrations of paclitaxel were used, EM012 promoted paclitaxel-induced microtubule polymerization both in vitro and in cultured cells. Nevertheless, EM012 enhanced the ability of nanomolar concentrations of paclitaxel to stabilize microtubules, as indicated by increased tubulin acetylation. Our results therefore suggest a therapeutic potential of EM012/paclitaxel combination in the management of human cancer and provide mechanistic insights into the combined effects of these two microtubule-targeting agents.     

Improved Air Quality and Attenuated Lung Function Decline: Modification by Obesity in the SAPALDIA Cohort

Background: Air pollution and obesity are hypothesized to contribute to accelerated decline in lung function with age through their inflammatory properties.Objective: We investigated whether the previously reported association between improved air quality and lung health in the population-based SAPALDIA cohort is modified by obesity.Methods: We used adjusted mixed-model analyses to estimate the association of average body mass index (BMI) and changes in particulate matter with aerodynamic diameter ≤ 10 µm (PM₁₀; ΔPM₁₀) with lung function decline over a 10-year follow-up period.Results: Lung function data and complete information were available for 4,664 participants. Age-related declines in lung function among participants with high average BMI were more rapid for FVC (forced vital capacity), but slower for FEV₁/FVC (forced expiratory volume in 1 sec/FVC) and FEF_25–75 (forced expiratory flow at 25–75%) than declines among those with low or normal average BMI. Improved air quality was associated with attenuated reductions in FEV₁/FVC, FEF_25–75, and FEF_25–75/FVC over time among low- and normal-BMI participants, but not overweight or obese participants. The attenuation was most pronounced for ΔFEF_25–75/FVC (30% and 22% attenuation in association with a 10-μg/m³ decrease in PM₁₀ among low- and normal-weight participants, respectively.)Conclusion: Our results point to the importance of considering health effects of air pollution exposure and obesity in parallel. Further research must address the mechanisms underlying the observed interaction.Citation: Schikowski T, Schaffner E, Meier F, Phuleria HC, Vierkötter A, Schindler C, Kriemler S, Zemp E, Krämer U, Bridevaux P-O, Rochat T, Schwartz J, Künzli N, Probst-Hensch N. 2013. Improved air quality and attenuated lung function decline: modification by obesity in the SAPALDIA cohort. Environ Health Perspect 121:1034–1039; http://dx.doi.org/10.1289/ehp.1206145     

Nutrition and health education through I.C.D.S

Summary results and discussion were provided for an Integrated Child Development Service (ICDS) survey of 52 anganwadi community workers (AWWs) and 156 mothers of ICDS beneficiary children. The project was implemented in Nelamangala, Bangalore, India, in order to ascertain the practices of mothers in managing diarrhea and respiratory infections and nutrition. The results would be applied to improving health education and developing appropriate and effective communication about nutrition and health between the AWW and the mother. The results of the AWWs survey showed that the 96.16% of AWWs had education up to the high school level and 2 graduated from high school. 69.2% weighed children correctly and 53.84% plotted growth charts satisfactorily. 53.50% of the 2507 growth charts were satisfactorily graphed. 94% reported weighing all children every month, however, the work load made this activity very difficult. Only 5.7% plotted the growth chart immediately after weighing. 38.46% found the visual record of growth good tool of health and nutrition education. 86.92% correctly identified a flattened curve as an indicator of growth failure. 71.15% were aware that additional feeding was needed. 17.30% suggested treatment with tonics and 3.84% suggested treatment for worm infestations. The responses from the mothers indicated that 51.92% were illiterate, agricultural laborers. 92% of mothers had a per capita income of less than Rs. 300/month. 86.53% were aware of the growth monitoring of the AWWS and 61% knew it was conducted monthly. 20.53% had participated in weighing sessions and 42% reported that AWWs explained the meaning of growth monitoring and the importance of weighing procedures. 28.84% reported that AWWs showed comparisons of present and previous weights and explained the significance. 38.64% considered the information meaningful, but only 3.84% could correctly interpret a flattened curve. 63.43% were misinformed about diarrhea causes and treatment. The recommendation was for use of arm circumference tapes for measuring malnutrition, for better training of AWWs in promoting extra feeding for malnutrition, for promoting continued breast feeding during diarrhea bouts, and discouraging use of over-the-counter drugs for treatment of respiratory infections.     

Voriconazole for the treatment of refractory Aspergillus fumigatus keratitis

We report a case of Aspergillus fumigatus keratitis in a 53-year-old, well-controlled diabetic female who did not respond to standard antifungal treatment. She was started on topical natamycin eye drops, but the infiltrate continued to progress. Topical amphotericin B and systemic ketoconazole was added, however, there was no response and the infiltrate increased further. She was then switched to topical and systemic voriconazole. Steady resolution of the infiltrate was noted within 2 weeks of therapy.