Tobacco habits and risk of lung, oropharyngeal and oral cavity cancer: a population-based case-control study in Bhopal, India

BACKGROUND: Tobacco habits in India are unique and vary in different regions. Few studies, and none from central India, have reported on type of tobacco used and risk of the most common cancer types in India. We conducted a population-based case-control study to evaluate the risk of tobacco particularly bidi smoking and tobacco quid chewing on the most common cancer sites among males in Bhopal. METHODS: In all, 163 lung, 247 oropharyngeal and 148 oral cavity cancer cases from the Population-Based Cancer Registry records and 260 controls randomly selected from a tobacco survey conducted in the Bhopal population formed the study population. RESULTS: A significant risk of bidi and cigarette smoking with a dose-response relationship was observed for lung and oropharyngeal cancer. Tobacco quid chewing showed no risk for lung, marginally increased risk for oropharyngeal and about a sixfold increased risk for oral cavity cancer. Population-attributable risk per cent (PARP) was observed to be 82.7% and 71.6% for smokers for the development of lung and oropharyngeal cancer, while the same was found to be 66.1% for tobacco chewers for the development of oral cavity cancer. CONCLUSIONS: These data provide strong evidence that smoking bidi is even more hazardous than cigarette smoking in the development of lung and oropharyngeal cancer. An intervention study to prevent the use of tobacco will be useful in this population as it also underwent gas exposure due to a chemical accident in 1984.     

Projected clustering of hyperspectral imagery using region merging

In this study, a novel method for clustering hyperspectral images is proposed. The proposed method performs projected clustering in feature/spectral space and merges regions in image/spatial space. The novelty of the proposed method lies in the way in which spectral and spatial information is used, along with its inclusion in the projected clustering framework. The proposed method transfers clusters formed in feature space to image space by converting them into regions. Then in image space, regions are iteratively merged by making use of spatial adjacency and spectral similarity. To evaluate the effectiveness of the proposed method, experiments are conducted on three hyperspectral images. The proposed method is also compared with other partitional clustering methods. Results demonstrate that the proposed method has ability to achieve better performance in most cases.     

Conservative management of type 2 gallbladder perforation in a child

Gallbladder perforation(GBP) is a rare but serious complication of cholecystitis and needs to be managed promptly. Acalculus cholecystitis leading to GBP is frequently associated with enteric fever and found in critically ill patients, and a surgical approach is not always feasible in such patients. Use of percutaneous tube cholecystostomy(PTC) in such patients is a known entity but it is usually followed by interval cholecystectomy. Here we report a case of perforated gallbladder in a child managed conservatively and successfully with PTC as the definitive treatment wherein cholecystectomy was avoided. The functionality of the gallbladder was confirmed by a Tc99m-HIDA scan.     

Linagliptin: a novel methylxanthin based approved dipeptidyl peptidase-4 inhibitor

Chemically, methylxanthine nucleus based Linagliptin (BI-1356, BI-1356-BS) is a dipeptidyl peptidase-IV inhibitor, which has been developed by Boehringer Ingelheim in association with Lilly for the treatment of Type-II Diabetes. Linagliptin was marketed by Lilly under the trade name Tradjenta and Trajenta. Linagliptin was approved as the once-daily dose by USFDA on 2 May 2011, for the treatment of Type-II Diabetes. Linagliptin 5mg once daily dose was approved based on a clinical trial program, which was conducted on approximately 4,000 adults with Type-II Diabetes. Linagliptin demonstrated statistically significant mean difference in HbA1c from placebo of up to 0.72 percent, when it was used monotherapically. In patients, who were not adequately controlled on metformin or metformin plus sulphonylurea, the addition of Linagliptin resulted in a statistically significant mean difference in HbA1c from placebo of -0.6 percent. Linagliptin was observed to produce significant reduction in fasting plasma glucose (FPG) compared to placebo, when used as a monotherapy in combination with metformin, sulfonylurea and/or pioglitazone. Linagliptin demonstrated significant reduction post-prandial glucose (PPG) levels in two hours as compared with placebo in monotherapy as well as in combination with metformin. In vitro assays also anticipated that Linagliptin is a potent DPPIV inhibitor as well as it exhibits good selectivity for DPP-IV as compared with other DPPs. The in-vivo studies also demonstrated same anticipation with respect to Linagliptin. Consequently, increasing the GLP-1 levels so far improved glucose tolerance in both healthy animals. X-ray crystallography anticipates that Linagliptin complexes with human DPPIV enzyme, e.g. butynyl substituent occupies the S1 hydrophobic pocket of the enzyme; the aminopiperidine substituent in the xanthine scaffold occupies the S2 subsite and its primary amine interacts with the key amino acid residues, which involves in the recognition of peptide substrates. In the present review, we have tried to cover comparative study of DPPIV inhibitors, chemistry, physical properties, commercial synthesis, patent portfolio, crystalline polymorphic forms of Linagliptin and its receptor interaction, Pharmacophore rational, mechanism, clinical studies, preclinical, adverse effect, available formulations, dose regimen, co-therapy of Linagliptin, giving emphasis on the medicinal chemistry aspects.     

Apixaban: a new player in the anticoagulant class

Apixaban (BMS-562247-01) is a compound being investigated as an anticoagulant. Apixaban molecule is developed in a joint venture by Pfizer and Bristol-Myers Squibb. Apixaban, a coagulation factor Xa inhibitor, approved in the E.U. in 2011 for the prevention of venous thromboembolic events in adult patients, who have undergone elective hip or knee replacement. The Apixaban based drug will be marketed under the brand name Eliquis? and is expected to rack up annual sales of over $2.5 billion. Apixaban is expected to provide stiff competition to warfarin, a popular blood thinner used in Europe. Warfarin is known to cause some serious side effects in patients. Apixaban, as compared with aspirin, reduced the risk of stroke or systemic embolism in patients experiencing atrial fibrillation by more than 50% (from 3.7% per annum with aspirin to 1.6% per annum with apixaban). Apixaban exhibits superiority to enoxaparin in preventing thrombosis in patients undergoing elective hip replacement surgery with similar bleeding rates. Apixaban is a highly selective and potent Factor Xa Inhibitor with Ki=0 8nM to both free as well as prothrombinase bound FXa. In X-ray crystal structure studies indicate that the pyrazole N-2 nitrogen atom interacts with backbone of Gln192 and the carbonyl oxygen of carboxamide interacts with NH of Gly216. The orientation of phenyllactum in the S4 region indiacates an edge to face interaction with Trp215, which is positioned between the Tyr99 and Phe174. In the present review, we have tried to cover comparative study of various FXa-inhibitors and point out apixaban in the various aspect including molecular chemistry, physical properties, commercial synthesis, current patent status, crystalline polymorphic forms, molecular receptor interaction, pharmacophore rational, mechanism of action, clinical studies, preclinical, adverse effect, available formulation, dose regimen and co-therapy, thus giving emphasis on medicinal chemistry aspects.     

Increased myeloperoxidase enzyme activity in plasma is an indicator of inflammation and onset of sepsis

Introduction

Circulating lipopolysaccharides released from bacteria may activate both neutrophils and monocytes. The activated neutrophils release myeloperoxidase (MPO), a specific enzyme with strong oxidative activity. The aim of this study was to evaluate MPO enzyme activity in plasma of critically ill patients and to check the hypothesis that these concentrations in plasma would be higher in sepsis and systemic inflammatory conditions, as neutrophils release their contents before proliferating in response to stress.

Material and Methods

Blood samples were collected from 105 critically ill patients admitted to the intensive care unit, consisting of those with systemic inflammatory response syndrome (n = 42), sepsis (n = 37), and septic shock (n = 26). Plasma MPO enzyme activity was determined by o-dianisidine-H₂O₂ method, modified for 96-well plates.

Results

The plasma MPO enzyme activity in sepsis patients was significantly higher than that in the control group (mean, 2.4 ± 1.8 in sepsis and 1.86 ± 1.2 nmol per milligram protein per 10 minutes in systemic inflammatory response syndrome vs 0.32 ± 0.11 nmol per milligram protein per 10 minutes in healthy controls). Mean plasma lactate levels in sepsis (7.8 ± 1.2 mmol/L) and shock patients (9.5 ± 1.2 mmol/L) and cytokines like tumor necrosis factor–α, interleukin-8, and interleukin-1β were simultaneously evaluated to establish onset of inflammation and sepsis. These results show that neutrophil activation occurring during inflammation and sepsis could be detected by plasma MPO concentration.

Conclusion

The plasma MPO concentrations may be a marker of the neutrophil proliferation and severity of inflammation.     

Atorvastatin Protects against Ischemia-Reperfusion Injury in Fructose-Induced Insulin Resistant Rats

Purpose  

High fructose (HFr) intake is known to cause insulin resistance syndrome (IRS), however its effect against acute coronary events remains elusive. The present study was undertaken to evaluate the effect of HFr (60%) diet on myocardial ischemia-reperfusion (MI-RP) injury and its modulation by atorvastatin treatment.     

Spectrum of HIV/AIDS related cancers in India

Objective To study the cancer pattern among HIV positive cancer cases. Method The study group included patients registered in the HIV Cancer clinic at the Tata Memorial Hospital (TMH), Mumbai, which is the largest tertiary referral cancer center in India. We used the gender and age-specific proportions of each cancer site of the year 2002 that was recorded in the Hospital Cancer Registry to estimate an expected number of various cancer sites among HIV positive cancer patients during the period 2001–2005. The observed number of site-specific cancer cases was divided by the expected number to obtain proportional incidence ratio (PIR). Results No case of Kaposi’s sarcoma was observed. Increased proportion of non- Hodgkin’s lymphoma (NHL) was observed (PIR in males = 17.1, 95%CI 13.33-21.84, females = 10.3, 95%CI 6.10-17.41).In males, PIR was increased for anal cancer (PIR = 10.3, 95%CI 4.30–24.83), Hodgkin’s disease, testicular cancer, colon cancer, and few head and neck cancer sites. Among females, the PIRs for cervical cancer (PIR = 4.1, 95%CI 2.90–5.75), vaginal cancer (PIR = 7.7, 95%CI 2.48–23.85), and anal cancer (PIR = 6.5, 95%CI 0.91–45.88) were increased. Conclusions The absence of Kaposi’s sarcoma and increased PIRs for certain non –AIDS defining cancers among HIV infected cancer cases indicates a different spectrum of HIV associated malignancies in this region. The raised PIR for cervical cancer emphasizes the urgent need for screening programs for cervical cancer among HIV infected individuals in India.