Role of cyclooxygenase activation and prostaglandins in antigen-induced excitability changes of bronchial parasympathetic ganglia neurons

In vitro antigen challenge has multiple effects on the excitability of guinea pig bronchial parasympathetic ganglion neurons, including depolarization, causing phasic neurons to fire with a repetitive action potential pattern and potentiating synaptic transmission. In the present study, guinea pigs were passively sensitized to the antigen ovalbumin. After sensitization, the bronchi were prepared for in vitro electrophysiological intracellular recording of parasympathetic ganglia neurons to investigate the contribution of cyclooxygenase activation and prostanoids on parasympathetic nerve activity. Cyclooxygenase inhibition with either indomethacin or piroxicam before in vitro antigen challenge blocked the change in accommodation. These cyclooxygenase inhibitors also blocked the release of prostaglandin D(2) (PGD(2)) from bronchial tissue during antigen challenge. We also determined that PGE(2) and PGD(2) decreased the duration of the action potential after hyperpolarization, whereas PGF(2alpha) potentiated synaptic transmission. Thus prostaglandins released during antigen challenge have multiple effects on the excitability of guinea pig bronchial parasympathetic ganglia neurons, which may consequently affect the output from these neurons and thereby alter parasympathetic tone in the lower airways.     

ABA, hydrogen peroxide and nitric oxide signalling in stomatal guard cells

Increased synthesis and redistribution of the phytohormone abscisic acid (ABA) in response to water deficit stress initiates an intricate network of signalling pathways in guard cells leading to stomatal closure. Despite the large number of ABA signalling intermediates that are known in guard cells, new discoveries are still being made. Recently, the reactive oxygen species hydrogen peroxide (H2O2) and the reactive nitrogen species nitric oxide (NO) have been identified as key molecules regulating ABA-induced stomatal closure in various species. As with many other physiological responses in which H2O2 and NO are involved, stomatal closure in response to ABA also appears to require the tandem synthesis and action of both these signalling molecules. Recent pharmacological and genetic data have identified NADPH oxidase as a source of H2O2, whilst nitrate reductase has been identified as a source of NO in Arabidopsis guard cells. Some signalling components positioned downstream of H2O2 and NO are calcium, protein kinases and cyclic GMP. However, the exact interaction between the various signalling components in response to H2O2 and NO in guard cells remains to be established.     

Ion chromatographic determination of thyroxine in urine

Thyroxine (3,5,3',5'-tetraiodo thyronine) is administered to patients suffering from endemic goiter as also in cases of non-iodine deficient ethiology and hypothyroidism. It is suggested that the uptake of thyroxine can be monitored by assessing the levels of the same in the urine of patients under treatment. For the purpose, a highly sensitive and selective ion chromatographic procedure is developed. The sample of urine is treated with sodium hydroxide and UV irradiated to convert iodine in thyroxine to iodide. Subsequently, iodide is separated on an anion exchanger AS 4A column using 50 mM NaOH as the eluent and determined spectrophotometrically at 226 nm.     

FNAC of Bacillus- Calmette- Guerin lymphadenitis masquerading as Langerhans cell histiocytosis

Bacillus Calmette Guerin (BCG) lymphadenitis is a well known entity. Disseminated BCG infection usually presents as generalized lymphadenopathy, skin rash and hepatosplenomegaly and at times, can pose a diagnostic challenge to clinicians. There are only a few published studies on the cytological findings of BCG lymphadenitis. In this letter we report the fine needle aspiration cytology (FNAC) of BCG lymphadenitis clinically masquerading as Langerhans cell histiocytosis (LCH). FNA smears showed sheets of foamy macrophages and many polymorphs in a dirty necrotic background with many macrophages as well as polymorphs showing negatively stained rod like structures within their cytoplasm. Zeihl Neelson stain revealed that these cells were heavily loaded with acid fast bacilli (AFB). In the index case, AFB were also seen within the cytoplasm of polymorphs, which has not been documented earlier in the literature.     

Sonic hedgehog pathway activation regulates cervical cancer stem cell characteristics during epithelial to mesenchymal transition

Resistance to therapy and metastasis remains one of the leading causes of mortality due to cervical cancer despite advances in detection and treatment. The mechanism of epithelial to mesenchymal transition (EMT) provides conceptual explanation to the invasiveness and metastatic spread of cancer but it has not been fully understood in cervical cancer. This study aims to investigate the mechanism by which silencing of E-cadherin gene regulates EMT leading to proliferation, invasion, and chemoresistance of cervical cancer cells through the Hedgehog (Hh) signaling pathway. We developed an in vitro EMT model by the knockdown of E-cadherin expression in cervical cancer cell lines. To understand the role of developmental pathway like Hh in the progression of cervical cancer, we investigated the expression of Hh pathway mediators by array in E-cadherin low cervical cancer cells and observed upregulation of Hh pathway. This was further validated on low passage patient-derived cell lines and cervical carcinoma tissue sections from cervical cancer patients. Further, we evaluated the role of two inhibitors (cyclopamine and GANT58) of the Hh pathway on invasiveness and apoptosis in E-cadherin low cervical cancer cells. In conclusion, we observed that inhibition of Hh pathway with GANT58 along with current therapeutic procedures could be more effective in targeting drug-resistant EMT cells and bulk tumor cells in cervical cancer.     

Theoretical studies on interaction of anticancer drugs (dacarbazine,procarbazine and triethylenemelamine) with normal (AT and GC) and mismatch (GG,CC, AA and TT) base pairs

This study is an attempt to gain a better understanding of the physicochemical interaction between novel anticancer drugs and DNA bases. We have employed quantum chemical tools to explore the interaction of a few anticancer drugs [namely procarbazine (PR), dacarbazine (DC) and triethylenemelamine (TR)] with isolated normal (GC and AT) and mismatch (AA, CC, GG and TT) base pairs. The molecular geometries, electronic structural stability, vibrational energies, chemical reactivity and other electronic properties were studied using MP2/6-311+G^**, B3LYP/6-311+G^** and M05-2X/6-311+G^** methods. The optimised geometries of the usual and mismatch base pairs are almost planar whereas the geometries of drug-interacting complexes deviate from planarity. The presence of steric hindrance and π-bond overlaps between C–C bonds in the complexes has distorted the planarity of the four- and five-member rings in the base pairs. Among the three drugs chosen, DC and PR bond well with normal and mismatch base pairs with large interaction energy. The electron density (ED) difference maps of the most stable GG–DC, GG–PR and GG–TR drug-interacting complexes show the information about sharing of ED and gain or loss of ED within the interacting molecules. The stabilisation energy of the charge transfer interaction between the relevant donor–acceptor orbital of GG–DC and GC–DC complexes has been found to be around 16 kcal/mol and GG–PR and GC–PR complexes has been found to be around 12 kcal/mol. But, for the GG–TR and GC–TR complexes, the stabilisation energy is found to be less than 6 kcal/mol. Moreover, the topological analysis of hydrogen bond network of DC and PR drug-interacting complexes have high electron and Laplacian density with structural stability at the bond critical points (BCPs), while compared TR drug-interacting complexes by atoms in molecules and natural bond orbital analysis. Finally, we may conclude that the drugs DC and PR are highly efficient drugs to target normal and mismatch base pair for control and inhibition of DNA replication.