Three metachronous primary lung cancers in a chronic smoker: A case report and review of the literature

Rationale:Lung cancer is a leading cause of cancer-related deaths. Smoking is major risk factor for initial and subsequent lung cancer especially in active smokers. Treatment of subsequent lung cancer depends on whether it is synchronous or metachronous. We report a rare case of triple metachronous lung cancer and review of literature of patients with triple metachronous cancers. This will be the second case reported of triple metachronous lung cancer.Patient concerns:A 60-year-old male, active smoker with diabetes mellitus, chronic obstructive pulmonary disease (COPD) and peripheral arterial disease presented with cough and hemoptysis. Initial computed tomography (CT) scan showed right upper lobe spiculated mass.Diagnosis:He underwent transthoracic needle biopsy for right upper lobe mass, showing primary lung adenocarcinoma (ADC)-Stage-IIIA. He continued to smoke and 9-years later had new left upper lobe spiculated nodule, which on surgical resection showed squamous cell carcinoma (SCC)-Stage-IA1. Despite counselling on smoking cessation, he was unable to quit. Six months later, he presented with shortness of breath and CT chest showing right hilar adenopathy in right upper and lower lobes. He underwent transbronchial biopsies of lesion which showed small cell lung carcinoma (SCLC).Interventions:His initial lung ADC-Stage-IIIA, was treated with chemotherapy, weekly thoracic radiation and additional chemotherapy cycles. Nine years later, his left upper lobe mass showing SCC-Stage-IA1 was deemed curative after apical resection and he was kept on surveillance. Six months later, after diagnosis of SCLC in right upper and lower lobe, patient was not a candidate for systemic chemotherapy due to poor performance status and opted for hospice care.Outcomes:His initial lung ADC-Stage-IIIA showed complete radiological response with chemotherapy and radiation. Subsequent SCC-Stage-IA1 was deemed curative after resection. Due to his poor performance status, he was not a candidate for chemotherapy for SCLC and patient opted for hospice care.Lessons:Smoking is a major risk factor for developing lung cancer and with continued smoking, patients are at higher risk for developing subsequent primary lung cancers. We recommend, patients with lung cancer must quit smoking, and those who do not, should remain on long-term surveillance.     

Periodontal disease in type 2 diabetes mellitus

Objective: To determine the periodontal status in well controlled and poorly controlled type 2 diabetic patients compared with normal healthy individuals. Study Design: Cross-sectional comparative study. Place and Duration of Study: Diabetes Management Centre, Services Hospital, Lahore, from November 2009 to January 2010. Methodology: Forty well controlled and forty poorly controlled type 2 diabetic subjects having good oral hygiene (scored according to simplified oral hygiene index) were compared with a control group of forty normal healthy individuals. Probing depth (PD), gingival recession (GR), and attachment loss (AL) were recorded to obtain the periodontal status of each tooth, using a Michigan probe "0" with Williams marking. Glycemic control was evaluated by glycated Hb value. Using ANOVA and independent sample t-test, mean probing depth and attachment loss in each tooth type (incisors, canines, premolars and molars) were compared. Results: Mean age of diabetic subjects was 58.86 ± 6.21 years and that of control group was 56.92 ± 6.91 years; 60% were females. Probing depth was greater in patients with poorly controlled diabetes compared to well controlled diabetic patients and non-diabetic controls (4.21 mm vs. 3.72 mm and 2.93 mm respectively, p < 0.001). Attachment loss also increased in poorly controlled diabetes (p < 0.001) compared to the control group and well controlled diabetes, however, the difference was not statistically significant when comparing well controlled to the control group (p > 0.05). Number of sites and mean percentage of sites with attachment loss of 3 4 and 3 6 mm was also significantly higher in poorly controlled diabetes compared to the control group (p < 0.05 and p < 0.001 respectively). Conclusion: Periodontal status as estimated by probing depth and degree of attachment loss deteriorates significantly with poor glycemic control in diabetes.     

A stimuli-responsive,superporous and non-toxic smart hydrogel from seeds of mugwort (Artemisia vulgaris): stimuli responsive swelling/deswelling,intelligent drug delivery and enhanced aceclofenac bioavailability

Artemisia vulgaris seeds extrude hydrogel (AVH), which shows extraordinary swelling in water, at pH 6.8, and 7.4, which follows second-order kinetics. AVH exhibits reversible swelling/deswelling in ethanol and normal saline as well at pH 7.4 and pH 1.2. Therefore, AVH shows stimuli-responsiveness in different physiological conditions, solvents, and electrolytes. The superporous nature of AVH in swollen/freeze-dried sculpture is exposed in their SEM micrographs. AVH-based aceclofenac tablet formulations offer sustained-release under simulated conditions of the gastrointestinal tract (GIT) in terms of pH and transit time. Pharmacokinetic studies also show the delay and prolonged plasma concentration with t_max of 8 h, therefore, such formulations can be used to enhance the bioavailability of aceclofenac. The swelling behavior of the AVH tablet is also assessed using MRI. The in vivo fate of the AVH tablet is monitored by X-ray during the transit through the GIT. Acute toxicity studies of AVH indicate the absence of any toxicity which reveals the safety profile of AVH. Therefore, AVH can be used for oral, topical and ophthalmic drug delivery systems. These results establish the potential of AVH as a stimuli sensitive, pH-dependent, and sustained-release biomaterial for targeted drug delivery.

Artemisia vulgaris hydrogel (AVH) was evaluated as a smart material for the development of sustained and intelligent drug delivery system for NSAIDs. AVH appeared to be a non-toxic material for possible biomedical and pharmaceutical applications.     

Cyclosporin-A Augments Respiratory Burst of Whole Blood Phagocytes in Pregnant Rats

Both pregnancy and cyclosporin A (CsA) are known to inhibit T-cell mediated immune response and to activate phagocytes against microbial infections as a compensatory mechanism. Pregnant women, either with organ transplantation or suffering from autoimmune diseases, are commonly managed with CsA therapy. This investigation was aimed to study effect of CsA on phagocytic activity of whole blood polymorphonuclear leukocytes (PMNs) in pregnant rats. Both pregnant and non-pregnant Sprague–Dawley rats (4 animals per group) were treated with CsA (40 mg/kg, oral) for 7 days starting from gestation day 7. Respective control groups of non-pregnant and pregnant rats received vehicle only. Luminol-dependent chemiluminescence (CL) was used to measure the generation of reactive oxygen species (ROS) in respiratory burst of whole blood PMNs stimulated by zymosan. The results showed a moderate and insignificant increase in CL response in non-pregnant rats with CsA treatment or pregnant rats without CsA treatment. Whereas the CL response of whole blood PMNs was significantly higher (ANOVA F?= 35.66, P < 0.001) in pregnant rats treated with CsA. In conclusion, this preliminary study demonstrates synergistic effects of pregnancy and CsA on activation of PMNs resulting in massive and sustained generation of ROS that could be deleterious to both host and fetus.     

Protective effects of tocotrienols against lipid-induced nephropathy in experimental type-2 diabetic rats by modulation in TGF-β expression

Dyslipidemia is common in patients with diabetes mellitus (DM) and is considered a risk factor for the progression of diabetic nephropathy (DN). Hyperlipidemia and hyperglycemia act synergistically to induce renal injury. The present study was designed to investigate the protective effects of tocotrienols as tocotrienol-rich fraction (TRF) extracted from palm (PO) and rice bran oils (RBO) against lipid induced nephropathy in type-2 diabetic rats and its probable molecular mechanism. Male Wistar rats (175–200 g) were divided into four groups. The first group served as diabetic control, while the second and third groups received PO-TRF and RBO-TRF, respectively by gavage over a period of sixteen weeks post-induction of diabetes. The fourth group comprised of age-matched rats that served as normal control. The effects of TRF on serum lipid profile, oxidative stress markers, expression of TGF-β, fibronectin and collagen type IV were analyzed in the kidney of diabetic rats. Treatment with PO-TRF and RBO-TRF significantly improved glycemic status, serum lipid profile and renal function in type-2 diabetic rats. In addition, TRF supplementation down-regulated the expression of TGF-β, fibronectin and collagen type IV in the kidney of diabetic rats. Transforming growth factor-β (TGF-β) plays a critical role in progression of DN, but its modulation by tocotrienols in DN remains unexplored. TRF ameliorated lipid induced nephropathy in type-2 diabetes by its hypoglycemic, hypolipidemic and antioxidant activities as well as by modulation of TGF-β to prevent increased expression of collagen type IV and fibrinogen. We finally propose a mechanism for the expression of molecular markers that are significant in the events leading to diabetic nephropathy and its modulation by tocotrienols/TRF.     

Significant impact of pace of eating on serum ghrelin and glucose levels

Objectives:To study the effect of normal versus slow eating on serum ghrelin, glucose, insulin, and C-peptide levels in healthy subjects from Riyadh, Saudi Arabia.Design and methods:The specified breakfast meal was served on two randomized occasions to 24 healthy volunteers to eat with a normal pace or at a slow rate. Venous blood samples were collected at 7 time points for biochemical analysis.Results:The slow ingestion of meals resulted in a significant increase in blood glucose and ghrelin levels as compared to normal pace of eating.Conclusions:Normal eating speed appears to be beneficial for maintaining the optimal blood glucose and ghrelin levels.     

Aversive Effects of Ethanol in Adolescent Versus Adult Rats: Potential Causes and Implication for Future Drinking

Background: Many people experiment with alcohol and other drugs of abuse during their teenage years. Epidemiological evidence suggests that younger initiates into drug taking are more likely to develop problematic drug seeking behavior, including binge and other high‐intake behaviors. The level of drug intake for any individual depends on the balance of rewarding and aversive effects of the drug in that individual. Multiple rodent studies have demonstrated that aversive effects of drugs of abuse are reduced in adolescent compared to adult animals. In this study, we addressed 2 key questions: First, do reduced aversive effects of ethanol in younger rats correlate with increased ethanol consumption? Second, are the reduced aversive effects in adolescents attributable to reduced sensitivity to ethanol’s physiologic effects? Methods: Adolescent and adult rats were tested for ethanol conditioned taste aversion (CTA) followed by a voluntary drinking period, including postdeprivation consumption. Multivariate regression was used to assess correlations. In separate experiments, adolescent and adult rats were tested for their sensitivity to the hypothermic and sedative effects of ethanol, and for blood ethanol concentrations (BECs). Results: We observed that in adolescent rats but not adults, taste aversion was inversely correlated with postdeprivation consumption. Adolescents also exhibited a greater increase in consumption after deprivation than adults. Furthermore, the age difference in ethanol CTA was not attributable to differences in hypothermia, sedation, or BECs. Conclusions: These results suggest that during adolescence, individuals that are insensitive to aversive effects are most likely to develop problem drinking behaviors. These results underscore the importance of the interaction between developmental stage and individual variation in sensitivity to alcohol.     

Traditional medicines of plant origin used for the treatment of inflammatory disorders in Pakistan:A review

OBJECTIVE:To pool data on ethnobotanical medicine for the treatment of inflammatory disorders in Pakistan.METHODS:We reviewed 237 research publications based on data from the six provinces in Pakistan(Punjab = 85,Khyber Pakhtunkhwa = 65,Sindh =15,Balochistan = 8,Gilgit Baltistan = 22,Azad Jammu and Kashmir = 42) published until June 2015 in various journals.This was achieved using seven online databases:Science Direct,Google,Google Scholar,Pub Med,Wiley Online Library,SpringerLink,and MEDLINE.Data were analyzed from different perspectives.RESULTS:People from Pakistan made use of 371 plant species belonging to 263 genera and 99 families for the treatment of inflammatory disorders.Plants from the Asteraceae family were used most often.Herbs were the dominant growth form.Leaves were the plant parts used most often.Decoctions were the main preparation method.Nine plant species were used most frequently in thedwellers of most regions of Pakistan.A total of 111 plants were shown experimentally to have neither anti-arthritic nor anti-inflammatory activities,and148 plant species were threatened.Eighty-four species had commercial importance.Twelve plant species were imported,and 25 plant species were exported,from Pakistan.CONCLUSION:This review provides baseline data for plant species in Pakistan that have potential anti-inflammatory/anti-arthritic activities.