A cell-based approach to study changes in the pancreas following nicotine exposure in an animal model of injury

Background Cigarette smoking is a recognized risk factor for the induction of pancreatic diseases and is suspected to play a major role in the development of pancreatic cancer in smokers. Materials and methods This study was designed to characterize the mechanisms of nicotine-induced injury to the pancreas. AR42Jcells, a stable mutant pancreatic tumor cell line, was chosen for the study because of its stability in culture media and also because of its known secretory capacity, which is like that of a normal pancreatic acinar cell. It is hypothesized that nicotine-induced effects on the pancreas are triggered by oxidative stress induced in pancreatic acinar cell via oxidative stress signaling pathways. Results The results from our study showed that, in vitro, nicotine induced generation of oxygen free radicals measured as malondialdehyde, an end product of lipid peroxidation. Treatment of AR42J cells with nicotine induced p-ERK 1/2 activation as confirmed by Western blot and immunofluorescence imaging of cytoplasmic localization of mitogen-activated protein kinase (MAPK) signals. Nicotine enhanced AR42J cell proliferation and cholecystokinin-stimulated amylase release in AR42J cells. These effects of nicotine were confirmed by simultaneous studies conducted on the same cells by hydrogen peroxide, a known oxidative biomarker. Allopurinol, a XOD inhibitor, suppressed these effects induced by nicotine and H₂O₂ with the exception that cholecystokinin-stimulated amylase release by H₂O₂ remained unaltered when AR42J cells were preincubated with allopurinol. These results suggest that nicotine-induced effects on pancreatic acinar cells were associated with generation of oxyradical mediated via the XOD pathway. The results have a direct impact on cell proliferation, MAPK signaling, and acinar cell function. Conclusion We conclude that nicotine induces oxidative stress in pancreatic acinar cells and that these events trigger pathophysiological changes in the pancreas, leading to increased cell proliferation and injury. A part of this communication was presented in the International Pancreatic Cancer meeting held on September 5–9, 2006, in Schloss Reisensburg, Ulm, Germany     

Multiple foreign bodies (open safety pins) in the oesophagus

Intra luminal hypopharyngeal and oesophageal foreign bodies are common. Among these the incidence of open safety pin is relatively uncommon and the occurrence of multiple open safety pins in the same ’ individual is a very rare phenomenon. Removal of one open safety pin itself is a surgical enigma, as inadvertant attempts at removal may cause the pointed end to get impacted submucosally or intramurally or may cause oesophageal tear and calls for the assistance of a thoracic surgeon. This article intends to highlight the occurrence of multiple open safety pins in the lumen of the oesophagus and its difficulty in successful retrieval.     

Newer trends in tubercular uveitis: a case series with systemic correlation

AIM: To determine the spectrum of uveitis, causes of visual loss in systemic tuberculosis, role of investigations and outcome after anti-tuberculosis treatment (ATT). METHODS: A retrospective study was conducted on 250 patients with systemic tuberculosis at a referral center in Chennai, South India from April 2016 to May 2019. Systemic workup comprised of Mantoux, chest X-ray, polymerase chain reaction (PCR) and QuantiFERON (QFT) TB Gold. Aqueous humor analysis by nested PCR or real time PCR (RT-PCR) and ancillary ophthalmic investigations such as fundus fluorescein angiography, optical coherence tomography were performed. RESULTS: Multifocal choroiditis and vasculitis were the most common manifestations and had a higher risk of recurrence. Pulmonary tuberculosis was more frequently associated with uveitis. Among those with extra-pulmonary tuberculosis miliary, bone and abdominal tuberculosis had uveitis. Complications such as cystoid macular edema, choroidal neovascular membranes and macular scarring caused visual loss. Aqueous humor analysis detected mycobacterium tuberculosis antigen. Collectively, systemic investigations such as chest X-ray, Mantoux test and those performed on blood samples such as PCR and QFT were positive in 39% of patients. In inconclusive patients, nested PCR and/or RT-PCR were done on aqueous humor samples and was diagnostic in 96%. A combination of tests was diagnostic in 92%. ATT in isolation in 71% and combined with corticosteroids in 29% was used for treatment of which signs of resolution and improvement in vision started as early as 6weeks in those who were started immediately on CS and ATT and longer than 3mo in those on ATT alone. Vision improved in 69%. Complete resolution occurred in 75% and worsening in 12%. CONCLUSION: A combination of investigations guided by clinical suspicion helps in precise diagnosis. In diagnostic dilemmas analysis of ocular samples is reliable and confirmatory. Prompt treatment with ATT and corticosteroids improved vision in 23% of our patients within 2mo. Vitritis with choroiditis causes cystoid macular oedema and requires longer duration of ATT. Screening all patients and a multidisciplinary approach in tuberculosis (active, healed or during treatment) is recommended.     

Exogenous administration of estradiol and cholecystokinin alters exocrine pancreatic function in rats

Summary This study was conducted in rats to investigate the influence of exogenously administered estradiol (ESD) and/or cholecystokinin (CCK) on components and secretions of the pancreatic acini. Intact male rats were treated for 14 d with exogenous administration of ESD, CCK, or ESD+CCK. After 14 d CCK treatment induced significant increases in DNA and RNA contents, and DNA/RNA ratio in the pancreas, indicating hyperplasia and hypertrophy of the pancreas, however, ESD treatment did not have these effects. Both ESD treatment and CCK treatment induced significant increases in amylase and trypsinogen contents in pancreatic acini and each decreased secretion from acini in response to CCK. Combined treatment with ESD plus CCK augmented these effects on enzyme contents and secretion. The results indicate that exogenous administration of CCK has trophic effects on the exocrine pancreas, increasing effects on enzyme contents and inhibitory effects on amylase secretion. In contrast, exogenous administration of ESD had no trophic effects on pancreas, but had increasing effects on enzyme contents and inhibitory effects on amylase secretion. The results suggest that the effects of exogenous ESD and CCK on pancreas are not similar to each other, but both ESD and CCK may be involved in regulating pancreatic exocrine functions.     

L-364,718, a new CCK antagonist,inhibits postprandial pancreatic secretion and PP release in dogs

The effects of L-364,718, a new CCK receptor antagonist, on food-stimulated exocrine pancreatic secretion and plasma levels of PP, insulin, CCK, and gastrin were examined in four conscious dogs with pancreatic fistulas. Intravenous injections of L-364,718 (20 nmol/kg) significantly inhibited pancreatic protein and enzyme responses by food (33% inhibition) but not juice volume output. Both rapid and secondary prolonged postprandial rises of plasma PP were also significantly suppressed by L-364,718 (50% inhibition); however, plasma levels of insulin were not altered. Postprandial levels of gastrin were not affected by L-364,718 administration, whereas 3-hr integrated CCK response was significantly enhanced by L-364,718. This study indicates that L-364,718 inhibits pancreatic protein and enzyme secretion and the release of pancreatic polypeptide stimulated by food in conscious dogs. This inhibition might be due to the selective blockage of receptor binding of circulating CCK molecules. The results suggest that L-364,718 may be useful for the physiological and pathophysiological studies associated with CCK.     

Eosinophilic ascites due to Strongyloides stercoralis.

We report the case of a patient with eosinophilic ascites in whom filariform larvae of Strongyloides stercoralis were found in smears of the ascitic fluid. The ascites resolved after therapy with albendazole. Eosinophilic ascites can rarely result from parasitic infections including Strongyloides stercoralis.     

Leptospirosis: clinical presentation and correlation with serovars

A total of 2400 patients with pyrexia of unknown origin and or suspected leptospirosis were included in this study. Dark field microscopy detected Leptospira in 690 cases, Leptospira serological Investigations proved positive in 570 out of these 690 patients. Among them 212 had the classical icteric and the other 358 had anicteric type of presentation. Notably eptospira interrogans serovar ictero haemorrhagiae infection was encountered in 212 patients. In 30 patients, who had multi organ dysfunction which included renal failure, hepatic dysfunction or meningitis was due to Leptospira interrogans Serovar cannicola. Coexsistense of leptospirosis and hepatitis B virus infection were noted in 15 patients. Antibody to Leptospira interrogans was demonstrated by Micro agglutination test (MAT) in addition to dark field microscopy positivity in these cases. Similarly HIV antibody was demonstrated in 30 of the 330 anicteric patients. 554 out of 570 cases responded to intra venous penicillin (216), and oral Doxycycline (182) and Augmentin (156), and the remaining 16 patients succumbed to death.     

Investigation on the effect of eclipta alba on animal models of learning and memory

Short and long term memory loss may result from deteriorating cerebral mechanisms due to varied causes which could have a tremendous impact on the quality of life. Herbs are being constantly explored to resolve cognitive deficits. Eclipta alba (Ea) commonly called as the trailing Eclipta is being examined for its memory enhancing quality as it is traditionally used for this purpose. The shade dried leaves of Eclipta alba was extracted with distilled water. The suspension of Ea containing 100 and 200 mg/kg was administered to rats to evaluate Transfer Latency (TL) on an elevated plus maze. TL was a measure of acquisition and retrieval learning. Mice were placed at the center of open field apparatus to assess spatial habitual learning, observed for 20 minutes for rearing and time spent during rearing using varied doses for 30 minutes, 24 hours and 96 hours and 144 hrs. The results revealed significant improvement of retrieval memory.