Effect of air pollution on peak expiratory flow rate variability.

Exposure to air pollution affects pulmonary functions adversely. Effect of exposure to pollution on diurnal variation of peak flow was assessed in healthy students. Three hundred healthy age-matched nonsmoker students were studied. They were categorized into two groups on the basis of their residence: commuters and living on campus. Peak expiratory flow (PEF) recordings were made twice daily for 2 days with the Pink City Flow Meter. The measurement was then used to calculate for each subject the amplitude percentage mean, which is an index for expressing PEF variability for epidemiological purposes (Higgins BG, Britton JR, Chinns Jones TD, Jenkinson D, Burnery PG, Tattersfield AE. Distribution of peak expiratory flow variability in a population sample. Am Rev Respir Dis 1989; 140:1368-1372). Air pollution parameters were quantified by measurement of sulfur dioxide (SO2), oxides of nitrogen (NO2), carbon monoxide (CO), and respirable suspended particulate matter (RSPM) in the ambient air at the campus and on the roadside. The mean values of PEF variability (amplitude percent mean) in the students living on campus and in the commuters were 5.7 +/- 3.2 and 11 +/- 3.6, respectively (P < .05). Among the commuters, maximum number of subjects showed amplitude percentage mean PEFR at the higher end of variability distribution, as compared to the students living on campus, among whom the majority of subjects fell in the lower ranges of variability distribution. The ambient air quality parameters, namely SO2, NO2, CO, and RSPM were significantly lower on the campus. It can be concluded that long-term periodic exposure to air pollution can lead to increased PEF variability even in healthy subjects. Measurement of PEF variability may prove to be a simple test to measure effect of air pollution in healthy subjects.     

Radiofrequency tissue ablation: an early Indian experience.

INTRODUCTION: Radiofrequency (RF) tissue ablation has been tried safely and effectively in the West as percutaneous local tissue ablation therapy. We present our experience with this technique in malignant lesions. METHODS: RF tumor ablation was done using an RF generator (Berchtold; Germany) generating 35-50 RF watts of power output. The RF needle was placed in the tumor under image guidance (n = 22) or at open surgery (n = 1). Around 1500 watts/cm3 RF energy was delivered to the tumor. Over 21 months, 23 patients underwent the procedure for 73 lesions, including metastatic liver lesions (n = 21) and locally advanced inoperable carcinoma of pancreas (n = 2). RESULTS: All lesions less than 3 cm in size (n = 15) and 39% of lesions 3-4 cm in size (17/44) had complete necrosis. Residual tumor was seen in 27/44 lesions (61%) 3-4 cm in size and in all 14 lesions more than 4 cm in size. There was no mortality or major morbidity. There were two minor complications (ascites 1, pleural effusion 1). Of 21 patients treated for liver metastases, 10 are still alive (6-month survival 19/21 [90%] and 12-month survival 11/17 [64.7%]). Only 2 of 32 (6.2%) lesions with complete necrosis had local recurrence. CONCLUSION: RF tumor ablation is a safe and effective local tissue ablative method in Indian patients.     

ASK1 associates with troponin T and induces troponin T phosphorylation and contractile dysfunction in cardiomyocytes

There is increasing support for the idea that excessive production of proinflammatory mediators such as tumor necrosis factor (TNF) and reactive oxygen species (ROS) contribute to the pathogenesis of cardiac dysfunction. However, the mechanisms by which cytokine/ROS production mediates cardiac dysfunction have not been established. Given that apoptosis signal-regulating kinase 1 (ASK1) is highly expressed in cardiac muscle and that ASK1 is an important mediator in the signaling pathways induced by tumor necrosis factor, interleukin-1, and ROS, we used the yeast two-hybrid system with ASK1 as bait to identify ASK1 substrates from a human heart cDNA library. The cDNA encoding the cardiac troponin T (cTnT) was isolated. ASK1 specifically interacted with cTnT, but not cTnI, in vitro and in vivo via the C-terminal ASK1 domain. ASK1 specifically phosphorylated cTnT in vitro and in vivo. Mutations in cTnT (T194/S198) at an ASK1-phosphorylation consensus sequence significantly reduced phosphorylation by ASK1. ROS-induced ASK1 activation, cTnT phosphorylation, and contractile dysfunction in cardiomyocytes showed similar kinetics. Moreover, overexpression of constitutively active ASK1 induces cTnT phosphorylation and inhibits shortening and calcium transient in adult cardiomyocytes. We conclude that ASK1 plays an important role in regulation of cardiac contractile function by phosphorylating cTnT and may participate in cytokine/ROS-induced pathogenesis of cardiomyopathy and heart failure.     

Androgenic Activity of Antiandrogens Predicted by Fit into DNA

Computer modeling including graphics and energy calculations were employed for the first time to examine the stereochemical fit of antiandrogens into double-stranded DNA. In this study, we assessed the relative fit of antiandrogens in the cavity between base pairs known to accommodate androgens. When compared to testosterone which was given a normalized value of 100%, the antiandrogens manifested the following order of fit: RU23908 (88%) > hydroxyflutamide (71%) > cyproterone acetate (41%). A correlation was observed between the relative fit of the antiandrogens and reported agonistic properties as assessed by the ability to increase nuclear androgen receptor levels in the rat ventral prostate. These findings may be useful in the design and development of androgen antagonists without agonistic activity.     

Biologics in Dermatology: An Integrated Review

The advent of biologics in dermatologic treatment armentarium has added refreshing dimensions, for it is a major breakthrough. Several agents are now available for use. It is therefore imperative to succinctly comprehend their pharmacokinetics for their apt use. A concerted endeavor has been made to delve on this subject. The major groups of biologics have been covered and include: Drugs acting against TNF-α, Alefacept, Ustekinumab, Rituximab, IVIG and Omalizumab. The relevant pharmacokinetic characteristics have been detailed. Their respective label (approved) and off-label (unapproved) indications have been defined, highlighting their dosage protocol, availability and mode of administration. The evidence level of each indication has also been discussed to apprise the clinician of their current and prospective uses. Individual anti-TNF drugs are not identical in their actions and often one is superior to the other in a particular disease. Hence, the section on anti-TNF agents mentions the literature on each drug separately, and not as a group. The limitations for their use have also been clearly brought out.