Synthetic and antibacterial studies on some new furanopeptides

A series of new furanopeptides (3) are prepared by the coupling of arylsubstituted furoic acids (1) with amino acid methyl esters, di and tetra-peptide methyl esters using dicyclohexyl carbodiimide (DCC) as coupling agent. Some of the newly synthesized compounds are characterized on the basis of IR, 1H NMR, mass spectral data and elemental analysis. Some of the selected compounds are also tested for their antibacterial properties.     

Approaches to vitamin B12 deficiency. Early treatment may prevent devastating complications

Vitamin B12 deficiency is a common problem that affects the general population and the elderly in particular. Persons with the deficiency may be asymptomatic or may have hematologic or neuropsychiatric signs and symptoms. If the disorder is untreated, complications may cause significant morbidity. In this article, Drs Dharmarajan and Norkus discuss approaches to screening and diagnosis as well as the nontoxic, low-cost treatments now available.     

Inhibitors of caspase homologues suppress an apoptotic phenotype in cultured rabbit corpora lutea

Apoptosis is a morphologically defined type of cell death initiated by various stimuli that results in the activation of caspases (cysteine-containing aspartate-specific proteases). In the present study, it was determined that caspases are present during, and play a role in, corpus luteum (CL) apoptosis in vitro. Pseudopregnancy was induced in rabbits with 100 IU human chorionic gonadotrophin. On Day 11 of pseudopregnancy, CL were isolated and cultured for 0, 2, 4, 6, and 8 h in the absence of trophic support to induce spontaneous apoptosis. Total RNA was extracted and analysed for caspase-I expression by Northern blot analysis. The results demonstrated caspase-I expression from 4 h. In the second part of the study, CL were incubated without trophic support for 4 h with increasing concentrations of three general caspase inhibitors, sodium aurothiomalate (SAM), iodoacetic acid (IAA) and N-tosyl-L-phenylalanylchloromethylketone (TPCK), and two specific caspase inhibitors, N-acetyl (Ac)-Tyr-Val-Ala-Asp (YVAD)-chloromethylketone (CMK) (Ac-YVAD-CMK) and Ac-Asp-Glu-Val-Asp (DEVD)-aldehyde (CHO) (Ac-DEVD-CHO). At completion, DNA was isolated and integrity assessed. Treatment of CL with SAM, IAA or Ac-DEVD-CHO effectively suppressed apoptotic DNA fragmentation. The final component of the study was to examine caspase-3 protein expression. Western blot analysis revealed a significant increase in caspase-3 expression over the experimental time-course. The results of the present study clearly demonstrate a time-dependent link between the caspases, specifically caspase-3 and spontaneous apoptosis in the rabbit CL.     

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.     

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.     

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.