Effect of kaempferol on lipid peroxidation and antioxidant status in 1,2-dimethyl hydrazine induced colorectal carcinoma in rats

Colorectal cancer, a common cause of cancer related deaths in both sexes in western population is often due to persistent oxidative stress leading to DNA damage. Antioxidants scavenge free radicals and inhibit neoplastic process. Kaempferol, a flavonol widely distributed in tea, broccoli, grape fruit, brussel sprouts and apple and is claimed to have chemopreventive action in colon cancer. The aim of our study was to evaluate the effect of kaempferol on tissue lipid peroxidation and antioxidant status in 1,2-dimethyl hydrazine induced colorectal cancer in male wistar rats and to compare its efficacy with irinotecan. Experimental colon cancer induced by 1,2-dimethyl hydrazine in rats mimic human colon cancer and therefore is an ideal model for chemoprevention studies. The rats were divided into six groups. Group 1 served as control. Group 2 received 1,2-dimethyl hydrazine (20 mg/kg body weight) subcutaneously once a week for four weeks. Group 3 received irinotecan (100 mg/kg body weight) intravenously once a week for four weeks with 1,2-dimethyl hydrazine. Groups 4 to 6 were given a daily oral dose of 50, 100, 200 mg/kg body weight of kaempferol with 1,2-dimethyl hydrazine. The total study period was 16 weeks. Kaempferol supplementation lowered 1,2-dimethyl hydrazine induced erythrocyte lysate and liver thiobarbituric acid reactive substances level and rejuvenated anti oxidant enzymes catalase, super oxide dismutase and glutathione peroxidase. The recovery of enzyme status was maximum at the dose of 200 mg/kg body weight and was comparable to irinotecan. Our study reveals that kaempferol could be safely used as a chemopreventive agent in colorectal cancer.     

Biological and chemical inhibitors of NF-kappaB sensitize SiHa cells to cisplatin-induced apoptosis

Cisplatin, a chemotherapeutic agent, is known to induce apoptosis of cancer cells. We examined the role of NF-kappaB during cisplatin-induced apoptosis in two human cervical cancer cell lines, HeLa and SiHa, known to differ in their response to cisplatin treatment. We found that SiHa cells were relatively more resistant than HeLa cells to the cytotoxic effects induced by cisplatin as measured by MTT assays. HeLa cells were more sensitive to the apoptotic effects induced by cisplatin as shown by increases in annexin staining, DNA fragmentation, and loss of mitochondrial membrane potential. Similarly the activities of caspases 3, 8, and 9 and cleavage of PARP induced by cisplatin were more in HeLa than SiHa cells. Cisplatin induced NF-kappaB DNA binding activity in HeLa and SiHa cells but not in primary cervical cells and the active DNA binding complex in SiHa cells consists of p50 and RelA heterodimers. However, when NF-kappaB DNA binding activity was blocked by chemical (curcumin, PDTC, or salicylic acid) or biological inhibitors (NIK-KM or IKK-beta DN), the cell viability was less in SiHa cells with cisplatin treatment, but these effects were not observed in HeLa cells. Similarly upon treatment with cisplatin SiHa cells had more activation of caspases compared to that seen in HeLa cells under conditions of NF-kappaB inhibition by biological or chemical inhibitors. These results suggest that NF-kappaB may contribute to the resistance of human cervical cancer cells to cisplatin and highlight the potential use of combination therapy involving cisplatin and NF-kappaB inhibitors.     

Iron Oxide Nanoparticles Induces Cell Cycle-Dependent Neuronal Apoptosis in Mice

Iron oxide (Fe₂O₃) nanoparticles (NPs) with its unique magnetic and paramagnetic properties are popular in biomedical applications. Some of their neurotoxic mechanisms due to repeated administration are proven. However, we speculate that the neuronal damage might be due to apoptosis resulting from unusual cell cycle entry. Moreover, iron accumulation has been shown to be closely associated with most of the neurodegenerative disorders. Thus, in the current study, mice were orally (po) treated with the Fe₂O₃-NPs to investigate cell cycle-associated events/components and occurrence of apoptosis. A subsequent increase in oxidant levels was observed with the iron accumulation due to Fe₂O₃-NPs exposure. The accumulated β-amyloid and reduced level of cdk5 seem to aid in the cell cycle entry and forcing progression towards apoptosis. Expression of Cyclin D1 and pRb (Ser 795) indicate the cell cycle re-entry of neurons. Overexpression of RNA Pol II and PARP cleavage suggests DNA damage due to Fe₂O₃-NPs exposure. Further, hyperphosphorylation of p38 (Thr 180/Tyr 182) confirms the activation of DNA damage-dependent checkpoint. Expression patterns of pro- and anti-apoptotic markers, TUNEL and TEM indicate the occurrences of apoptosis.     

Crazy vaping and crazy-paving,a case of E-Cigarette/Vaping-Associated Lung Injury (EVALI) with chest CT showing crazy-paving pattern

E-cigarettes are devices that generate an aerosol by heating a fluid containing multiple chemicals, such as nicotine, additives, and flavorings. They were developed to aid in smoking cessation and were promoted as socially acceptable, healthier, cheaper than conventional cigarettes. Multiple lung disorders related to e-cigarette use are reported, and they range from mild cases of pneumonitis to life-threatening lung disorders that may require intubation and mechanical ventilation. Most of the complications are due to the generation of various unknown and potentially harmful chemicals within the aerosol generated in the e-cigarette. These disorders are known collectively as e-cigarette/Vaping-associated lung injury (EVALI). E-cigarettes are marketed as safer alternatives to traditional cigarettes, with the highest rates of use are noted in young smokers. Given the significant prevalence of e-cigarettes use and their pulmonary complications, EVALI should be considered a potential etiology in the broad differential diagnosis of patients with pulmonary disease and a history of vaping. Herein, we present a case of cryptogenic organizing pneumonia with a chest C.T. showing a crazy-paving pattern in a patient with a history of vaping.     

Conscious sedation: A dying practice?

Sedation practices vary according to countries with different health system regulations, the procedures done, and local circumstances. Interestingly, differences in the setting in which the practice of gastroenterology and endoscopy takes place (university-based vs academic practice) as well as other systematic practice differences influence the attitude of endoscopists concerning sedation practices. Conscious sedation using midazolam and opioids is the current standard method of sedation in diagnostic and therapeutic endoscopy. Interestingly, propofol is a commonly preferred sedation method by endoscopists due to higher satisfaction rates along with its short half-life and thus lower risk of hepatic encephalopathy. On the other hand, midazolam is the benzodiazepine of choice because of its shorter duration of action and better pharmacokinetic profile compared with diazepam. The administration of sedation under the supervision of a properly trained endoscopist could become the standard practice and the urgent development of an updated international consensus regarding the use of sedative agents like propofol is needed.     

Handheld Metal Detector for Metallic Foreign Body Ingestion in Pediatric Emergency

Objective

Foreign body ingestion is a common problem for which children present to the emergency department. The most common ingested foreign bodies among children are coins. Metal detector is an equipment, which measures a change in inductance of a coil when an electroconductive material is placed near it and produces an audio-visual signal. The present study was conducted to determine the effectiveness and feasibility of HMD in the local Pediatric population.

Methods

This was a prospective study conducted in the pediatric emergency department among children presenting with history of foreign body ingestion. The outcome measured was presence or absence of metallic foreign body detected on handheld metal detector examination.

Results

During the study period, 36 patients with history of foreign body ingestion presented to the emergency department. Among these, 28 were metallic foreign body ingestions. Coins were the most common type of foreign body ingested. Among the metallic foreign bodies ingested, all the coins were accurately identified by the handheld metal detector. Non-coin metallic foreign bodies like metallic screw, needle and stapler pin were not identified by the handheld metal detector.

Conclusions

The study demonstrates that handheld metal detector can be safely and reliably used as a screening tool in the process of detecting ingested coins. The plain radiograph still appears to be superior as it accurately localizes sharp metallic objects as well as cell batteries (button batteries) which need to be detected early and removed in order to prevent complications. Handheld metal detector is an effective tool that can be used in the follow up of patients to confirm whether the coin like metallic foreign body has been expelled. Handheld metal detector examination is more sensitive than traditional X-ray examination to detect radiolucent metallic foreign bodies like aluminium.