Role of CTLA4 immunohistochemistry in the diagnosis of colon cancers

Background: There are a wide range of diagnostic markers for colorectal cancers like detection of mutated KRAS, TP53, and APC genes. However, genetic and immunological factors have also been attributed to the cancer prognosis. The present study was carried out to evaluate the expression of CTLA-4 in colorectal cancers. Methods: This cross-sectional study was carried out among 30 resected specimens of colorectal cancer. Paraffin blocks were made on samples from tumor areas along with adjacent normal areas. Immunohistochemistry for CTLA-4 was done on the sections along with controls. Gross findings were recorded from the blocks. Blocks with section containing normal epithelium and tumor were chosen for immunohistochemistry. Results: Overexpression of CTLA-4 was observed in 43.3% of the tumors. There was a significantly high tumor infiltration among those specimens showing overexpression of CTLA-4. The observed difference was statistically significant (P < 0.05). On comparing the grade of the tumor with intensity of CTLA4 uptake, it was observed that majority of the well-differentiated tumors (66.7%) had an intensity of 1+ whereas majority of the poorly differentiated tumors had an intensity of 3+ (66.7%). Conclusion: The present study has demonstrated overexpression of CTLA-4 in colorectal cancer specimens, and also highlighted the potential scope for anti-CTLA-4 agents like Ipilimumab in cancer therapy. The need for further evaluation to examine five-year survival with such immunotherapies is essential to document candid therapeutic recommendations for colorectal cancers.

Enhanced cytotoxic effect on human lung carcinoma cell line (A549) by gold nanoparticles synthesized from Justicia adhatoda leaf extract

Objective: To synthesize bio-inspired gold nanoparticles (AuNPs) using the leaf extract of Justicia adhatoda and evaluate the anti-cancer activity on human lung cancer cell line (A549). Methods: Synthesis of AuNPs was done using an aqueous leaf extract of Justicia adhatoda as a green route. The bio-synthesized AuNPs were confirmed and characterized by using various spectral studies such as UV-Vis spectrum, Scanning Electron Microscope with EDAX, Transmission Electron Microscope, Fourier Transmission Infrared Spectroscope analysis and Surface Enhanced Raman Spectroscopy. The cell viability was determined by MTT reduction assay. In addition, cytomorphology and the nuclear morphological study of A549 cell line was observed under fluorescence microscope. Results: UV-Vis spectrum showed surface plasmon resonance peak at 547 nm, scanning electron microscope and transmission electron microscope studies showed the monodispersed spherical shape and its average size in the range of 40.1 nm was noticed. Fourier Transmission Infrared Spectroscope analysis confirmed that the C=O group of amino acids of proteins had strong ability to bind with the surface of nanoparticle. Interestingly, our results also demonstrated inhibited proliferation of A549 cell line by MTT (IC50 value: 80 μg/mL). Cell morphology was observed and cell death was caused by apoptosis as revealed by propidium iodide staining. Conclusions: The current study proves the anticancer potential of bio-synthesized AuNPs. Thus, synthesized AuNPs can be used for the treatment of human lung cancer cell (A549) and it can be exploited for drug delivery in future.

Screening of cetirizine for analgesic activity in mice.

Background: Pain is the most common symptom for which patients approach doctors. We have multitude of drugs for pain relief, but they have serious side effects ranging from peptic ulcer (e.g. NSAIDs) to renal failure. The other group, opioids have well known side effects ranging from sedation to drug dependence. So a search for a drug for analgesia with high therapeutic effect and fewer side effects will be a boon for the patients. The objective of this study was to find whether cetirizine, a second generation antihistaminic drug, has got any analgesic activity in mice. Methods: Ten adult albino mice weighing 20-30 grams of either sex were randomized to two groups (n=5). Group I: control group (Treated with solvent 0.1 ml/kg), Group II: Test group (Cetirizine 1mg/kg). All drugs were given orally. The analgesic activity was evaluated by using tail flick, tail immersion and tail clip methods. Reaction time of animals to pain sensation before and after Cetirizine administration were noted at 0, 15, 30, 60 and 90 minutes time intervals respectively on Day 1, 3, 5, 7, 10. Results: Mean reaction time was expressed as Mean±SEM, and one way ANOVA was used to assess statistical significance. Cetirizine was found to have statistically significant analgesic effect in mice and time dependent increase in analgesic effect were observed in all three pain models and maximum analgesic activity was observed at 60 minutes (p<0.001) after drug administration. Conclusions: Through this study, Cetirizine, a second generation antihistamine, is found to have significant analgesic activity in mice. This effect has to be studied further elaborately in animals as well as in humans.

Tropical pancreatitis and fibrocalculous pancreatic diabetes--two sides of the same coin?

Tropical pancreatitis and fibrocalculous pancreatitic diabetes are usually considered two ends of the same disease although some studies suggest the likelihood of distinct entities. We report the occurrence of these two diseases in two siblings. The literature comparing the similarities and differences between them is briefly reviewed.

Acute pancreatitis in viral infections, with possible progression to chronic pancreatitis.

Isolated cases and small series of acute pancreatitis complicating viral infections have been reported. However, data on the natural history of such patients are sparse. We report a series of five patients of acute pancreatitis complicating diverse viral infections. During follow-up ranging from 6 to 36 months, two of these five patients developed evidence of chronic pancreatitis.

Prevention awareness counselling and evaluation (PACE) diabetes project: a mega multi-pronged program for diabetes awareness and prevention in South India (PACE- 5).

OBJECTIVE: The Prevention Awareness Counselling Evaluation (PACE) Diabetes Project is a large scale community based project carried out to increase awareness of diabetes and its complications in Chennai city (population: 4.7 million) through 1) public education 2) media campaigns 3) general practitioner training 4) blood sugar screening and 5) community based "real life" prevention program METHODS: Education took place in multiple forms and venues over the three-year period of the PACE project between 2004-2007. With the help of the community, awareness programs were conducted at residential sites, worksites, places of worship, public places and educational institutions through lectures, skits and street plays. Messages were also conveyed through popular local television and radio channels and print media. The General Practitioners (GPs) program included training in diabetes prevention, treatment and the advantages of early detection of complications. Free random capillary blood glucose testing was done for individuals who attended the awareness programs using glucose meter. RESULTS: Over a three-year period, we conducted 774 education sessions, 675 of which were coupled with opportunistic blood glucose screening. A total of 76,645 individuals underwent blood glucose screening. We also set up 176 "PACE Diabetes Education Counters" across Chennai, which were regularly replenished with educational materials. In addition, we trained 232 general practitioners in diabetology prevention, treatment and screening for complications. Multiple television and radio shows were given and messages about diabetes sent as Short Message Service (SMS) through mobile phones. Overall, we estimate that we reached diabetes prevention messages to nearly two million people in Chennai through the PACE Diabetes Project, making it one of the largest diabetes awareness and prevention programs ever conducted in India. CONCLUSION: Mass awareness and screening programs are feasible and, through community empowerment, can help in prevention and control of non-commuincable diseases such as diabetes and its complications on a large scale.

Fulminant hepatic failure for herpes simplex virus.

Although exceedingly rare, fulminant hepatic failure in immunocompetent patients can develop with primary or recurrent infection due to herpes simplex virus. The diagnosis is frequently obscured by the absence of mucocutaneous involvement. Elevated transaminases with leucopenia and a relatively low bilirubin level may provide clues to the diagnosis. Here a female patient, 43 years, presented with the complaints of increasing jaundice, anorexia, nausea, vomiting for one week duration. She had hepatomegaly. Investigations revealed markedly raised transaminases and coagulopathy. Herpes simplex virus IGM (by ELISA) was positive. The immunocompetent woman was treated with acyclovir but the result was fatal.

Tropical pancreatitis - a distinct entity, or merely a type of chronic pancreatitis?

Tropical pancreatitis was described 50 years ago as a disease of the tropical regions, particularly southern India, with young age at onset, malnutrition, rapid progression, severe pancreatic damage with multiple large ductal calculi, and absence of history of alcoholism or biliary tract disease as its hallmarks. Over the years, chronic pancreatitis in southern India has shown a change, with increase in older patients, occurrence of milder disease including milder diabetes, increasing longevity, and increasing association with alcoholism and smoking. This article looks at changes in the disease and in dietetic, environmental and socioeconomic factors over the years, in an attempt to understand the environment-gene interactions in its causation. This analysis shows that tropical pancreatitis may represent one end of the wide spectrum of chronic pancreatitis in the tropics, with alcoholic pancreatitis representing the other extreme.

A clinical profile to assess the potential risk factors for cleft lip and palate.

Cleft lip and palate is one of the most common malformations in man. Although the subject of a great deal of investigation, etiologic factors contributing to these congenital deformities remain largely unknown. Various factors like race, sex, parental age at the time of conception etc. have been listed as the exogenous factors. This article strives to project any significant relationship of these factors to cleft lip and cleft palate.

Oxidative stress in alcoholic liver disease.

We report on the prooxidant (lipid peroxides) and antioxidant levels (ascorbic acid, reduced glutathione, superoxide dismutate activity) in healthy individuals (30) and patients with cirrhosis (37; 22 alcoholic cirrhosis and 15 non alcoholic cirrhosis). A significant increase in plasma lipid peroxide (P < 0.05) and ascorbic acid (P < 0.01) and a significant decrease in reduced glutathione (P < 0.001) and superoxide dismutase activity (P < 0.05) in haemolysate was observed in cirrhosis patients compared to the control group. A significant decrease in reduced glutathione (P < 0.01) and superoxide dismutase (P < 0.05) activity was also observed when the alcoholic cirrhosis group was compared to non alcoholic group. A significant increase in aspartate transaminase (P < 0.05), gamma glutamyl transaminase (P < 0.01) and aspartate transaminase/alanine transaminase (P < 0.05) ratio was seen in alcoholic cirrhosis group. A significant positive correlation between gamma glutamyl transferase and lipid peroxides (r = 0.48, P < 0.05) was observed in alcoholic cirrhosis.

Ranitidine for the prevention of complications following endoscopic sclerotherapy for esophageal varices.

Thirty one patients with significant esophageal variceal bleed were allocated alternately to receive endoscopic sclerotherapy along with ranitidine 300 mg daily or endoscopic sclerotherapy alone till eradication of varices. The mean sclerotherapy sessions, time and volume of sclerosant required for obliteration of varices were similar for the two groups. The esophageal varices were eradicated in all the patients except three in sclerotherapy alone group. There was statistically significant reduction in frequency of post sclerotherapy mucosal ulcers (P < 0.05) after addition of ranitidine to sclerotherapy. Rebleeding was not only significantly reduced (P < 0.05) in the sclerotherapy with ranitidine group but was minor and did not even require blood transfusion. In sclerotherapy alone group rebleeding was controlled by surgery in two patients and one died due to massive bleeding. The results of this study suggest a beneficial role of ranitidine in reducing post sclerotherapy mucosal ulcers and rebleeding. This effect of ranitidine emphasises the role of acid-pepsin in pathogenesis of these ulcers and its associated morbidity.