Columnar lined (Barrett's) esophagus: future perspectives

Columnar lined esophagus (CLE) or Barrett's esophagus is the precursor for esophageal adenocarcinoma. Future advances in understanding and management of this condition as well as improving the quality of care of CLE patients depends on answering essential questions. It is important to standardize the criteria for CLE definition. The rapid increase in incidence of CLE and adenocarcinoma raises serious concerns that the current management of gastroesophageal reflux disease (GERD) needs reassessment. The risk factors that determine who will and will not develop CLE are as yet undetermined. There is a need to develop a clinical risk stratification tool, which will help in determining who should be screened. The impact of elimination of GERD on the natural history of CLE is one important area for future research. The benefit of surveillance strategies remains unproven and the ideal endoscopic frequency, protocols and markers of cancer risk are unknown. Dysplasia may not provide the gold standard marker of cancer risk because of some inherited problems. A better technique than the current endoscopic pinch biopsy protocol is needed. To overcome the limitations of histological markers, many other markers of cancer risk needs to be developed and validated. The key question as to whether cancer risk is actually reduced by the new ablation modalities remains unanswered. The natural history of dysplasia and its management needs to be clarified. Although many questions have to be answered, it seems, however, that at least some answers exist, and these and proposals for answering some of these questions are underlined throughout this review.     

Current status of newer antiinfectives

In the era of multidrug resistance keen interest needs to be taken in developing newer antiinfective drugs and patents. We all are aware that not many such drugs are readily available and still less are in the pipeline, and thus, such patents are limited in number. This is an attempt to review some of the newer antiinfectives used as antibacterial, antifungal and antiparasitic agents. An attempt has been made here to review the lately added newer antiinfectives. However, there has not been much change in the antiparasitic drug development arena. But it is interesting to note that even much older antiparasitic formulations are still of much use and the reason for this is reviewed here. Among the antibacterial drugs ertapenem, gemifloxacin, tigecycline and daptamycin are discussed. Doripenem has not been included here, due to the paucity of randomized trials of the molecule; however, it appears to be a promising penem that is to get added to the list of available antibiotics. The antiparasitic and antifungal drugs have attracted major attention of the research scientists and clinicians because of the increasing incidence of parasitic and fungal infections in the immunocompromised patients, leading to added morbidity and mortality. In the present review, besides newer antibiotics, newer anti parasitic and antifungal drugs have also been discussed.     

Differential growth of the freshwater mussel, Lamellidens marginalis in relation to certain drugs

The survival and growth rate of the Indian freshwater mussel, Lamellidens marginalis, (Lamarck) was ascertained in cultivation by using certain drugs in CIFA, fish farm, BBSR (India) during June 1998 to February 1999.Two sets of experiments were carried out to evaluate the effects of drugs like Betamethasone, Calcium, Azathioprine, Stanazolol, and Folic acid. Chloramphenicol was added with each treatment as prophylaxis to prevent the bacterial growth. In the first set, the inactiveness and mortality of the mussels in different drugs were studied through two different dosages and in subsequent tests the fixation of dosage was employed. The study in the second set was regarding the survival, increment of shell length, its thickness, and wet weight in response to different drugs therapy. The drugs were administered parenterally in "fixed dosage" at a regular interval of 21-23 days. The survival rate was good with Betamethasone and Azathioprine that is 75%, whereas it was 16.66% in Folic acid treatment. But the mussels originating from the control site had the significant survival rate though the growth rate was average. Calcium treatment had shown a marked increment of shell thickness and luster. The culture was lasted for 160 days. The wet weight gain of mussels in all the treatments were significant, p<0.0001 whereas increment of shell thickness was significant only in treatment B (Calcium) and treatment D (Azathioprine), p<0.0001 but with regard to the increment of length of mussel, treatment E (Stanazolol) was not significant, p>0.05. The regression analysis was adopted to find out the coefficient of determination (R(2)=0.90, being the best) from the relationship between length and weight of mussels and to establish the LWR equation with condition factor k=W/L(b).     

Rifampicin, ethambutol and pyrazinamide-induced thrombocytopenia

Drug-induced thrombocytopenia is an uncommon but serious side effect of many drugs including antituberculosis drugs. It is difficult to diagnose but easy to prevent just by stopping the exposure to the same drug again. In some cases, it can prove fatal if not taken care of urgently. Here, we report a case of thrombocytopenia due to rifampicin, ethambutol and pyrazinamide all in an adult male, which we believe is the first to be reported.     

Quantification of levetiracetam in human plasma by liquid chromatography-tandem mass spectrometry: application to therapeutic drug monitoring

A rapid, selective, reliable, precise, accurate, and reproducible tandem mass spectrometric (MS-MS) method for the quantification of levetiracetam (LEV) in human plasma using adenosine as an internal standard (IS) has been developed and validated. The drug and IS were extracted by solid phase extraction (SPE) technique and analyzed on Symmetry((R)) C(18) column (5 microm, 3.9 mm x 50 mm) using a mobile phase of methanol-water-formic acid (97:03:0.25, v/v/v) at a flow rate of 0.2 ml/min. Quantitation was achieved using a positive electrospray ionization (ESI+) interface employing multiple reaction monitoring (MRM) mode at MRM transitions m/z 171>126 and m/z 268>136 for LEV and IS, respectively. The method was validated over the concentration range of 1.0-40 microg/ml (r>0.99) with a limit of quantification of 1.0 microg/ml (R.S.D.%; 4.1 and Bias%; -9.0 to + 11.0%). Intra- and inter-run precision of LEV assay at three concentrations ranged from 0.6 to 8.9% with accuracy (bias) varied from -4.0 to 8.6% indicating good precision and accuracy. Analytical recoveries of LEV and IS from spiked human plasma were in the range of 91.7-93.4% and 80.2-84.1%, respectively. Stability of LEV in human plasma samples at different conditions showed that the drug was stable under the studied conditions. Matrix effect study showed a lack of matrix effect on mass ions of LEV and IS. The described method compared well with the commercial HPLC-UV method of Chromsystem (r(2)=0.99). The suitability of the developed method for therapeutic drug monitoring was demonstrated by measuring LEV in human plasma samples of epileptic patients treated with LEV.     

Novel molecular targets for antimalarial drug development

Malaria with one million deaths and about 500 million new cases reported annually is a challenge to drug therapy and discovery. As current antimalarial therapeutics become increasingly ineffective because of parasitic resistance, there exists an urgent need to develop and pursue new therapeutic strategies. Antimalarial drug development can follow several strategies, ranging from minor modifications of existing agents to the design of novel agents that act against new targets. Recent advances in our knowledge of parasite biology as well as the availability of the genome sequence provide a wide range of novel targets for drug design. Several promising targets for drug intervention have been revealed in recent years. This review discusses novel molecular targets of the malaria parasite available to the drug discovery scientist.