Herpes Simplex Virus Pseudotumor Masking as Gastric Malignancy.

Herpes simplex virus (HSV) pseudotumor is a rare presentation of HSV and has not been previously reported in the stomach. A 51-year-old man with a medical history of HIV presented with new-onset dysphagia. Endoscopy revealed an HSV-positive mass at the gastroesophageal junction. After antiviral treatment, the patient returned with a 100-pound unintentional weight loss. Computed tomography showed an infiltrative mass with enlarged lymph nodes. The mass had progressed despite HSV treatment, and a repeat set of biopsies were negative for HSV with cells concerning for B-cell lymphoma. The patient was taken to the operating room for a full-thickness biopsy because of increasing concern for malignancy. The procedure was complicated by gastric perforation, leading to a total gastrectomy. Final pathology demonstrated an HSV-positive pseudotumor, negative for malignancy. It is important to diagnose gastric masses, especially in HIV-positive patients at high risk of infection and malignancy. However, immunocompromised patients with an HSV-positive mass should be treated for HSV pseudotumor with a longer than standard duration of antiviral therapy.

MicroRNAs as master regulators of FOXO transcription factors in cancer management.

MicroRNAs are critical regulators of the plethora of genes, including FOXO "forkhead" dependent transcription factors, which are bonafide tumour suppressors. The FOXO family members modulate a hub of cellular processes like apoptosis, cell cycle arrest, differentiation, ROS detoxification, and longevity. Aberrant expression of FOXOs in human cancers has been observed due to their down-regulation by diverse microRNAs, which are predominantly involved in tumour initiation, chemo-resistance and tumour progression. Chemo-resistance is a major obstacle in cancer treatment. Over 90% of casualties in cancer patients are reportedly associated with chemo-resistance. Here, we have primarily discussed the structure, functions of FOXO and also their post-translational modifications which influence the activities of these FOXO family members. Further, we have addressed the role of microRNAs in carcinogenesis by regulating the FOXOs at post-transcriptional level. Therefore, microRNAs-FOXO axis can be exploited as a novel cancer therapy. The administration of microRNA-based cancer therapy is likely to be beneficial to curb chemo-resistance in cancers.

Renal cell carcinoma management: A step to nano-chemoprevention.

Renal cell carcinoma (RCC) is one of the most common kidney cancers, responsible for nearly 90 % of all renal malignancies. Despite the availability of many treatment strategies, RCC still remains to be an incurable disease due to its resistivity towards conventional therapies. Nanotechnology is an emerging field of science that offers newer possibilities in therapeutics including cancer medicine, specifically by targeted delivery of anticancer drugs. Several phytochemicals are known for their anti-cancer properties and have been regarded as chemopreventive agents. However, the hydrophobic nature of many phytochemicals decreases its bioavailability and distribution, thus showing limited therapeutic effect. Application of nanotechnology to enhance chemoprevention is an effective strategy to increase the bioavailability of phytochemicals and thereby its therapeutic efficacy. The present review focuses on the utility of nanotechnology in RCC treatment and chemopreventive agents of RCC. We have also visualized the future prospects of nanomolecules in the prevention and cure of RCC.

Choline chloride attenuates the allergic airway disease by inhibiting the lysophosphatidylcholine induced response in mouse model.

Aims: Allergic airway disease manifestation is induced by lysophosphatidylcholine (LPC) through CD1d-restricted Natural killer T (NKT) cells. Choline chloride (ChCl) and LPC both have the "choline" moiety in their structure and this may interplay the effect in allergic airway disease pathway. Main methods: To test the hypothesis, mice were sensitized with cockroach extract (CE); challenged with CE or exposed to LPC and were given ChCl 1hr later. Key findings: A significant increase in Airway hyperresponsiveness (AHR), total and differential cell count, Th2 cytokines, 8-isoprostanes level in bronchoalveolar lavage fluid (BALF) and inflammation score based on lung histology were observed on challenge with CE or exposure to LPC (p â€‹< â€‹0.05) indicating LPC induced airway disease manifestation in mice. These parameters were reduced significantly after administering mice with ChCl (p â€‹< â€‹0.05). The inflammatory parameters were significantly increased in LPC exposed mice, not sensitized with CE, which were significantly decreased when mice were administered with ChCl demonstrating its role in the inhibition of LPC induced allergic airway disease manifestation. Docking of CD1d with LPC and ChCl indicated the competitive inhibition of LPC induced effect by ChCl. This was validated in vivo in the form of decreased CD1d-restricted NKT cells in BALF and lung of the immunized mice on ChCl administration. There was no effect of ChCl administration on CD1d expression in BALF and lung cells. Significance: This study shows that ChCl attenuates the allergic response by inhibiting the LPC induced- NKT cell mediated AHR, inflammation and oxidative stress by competitive inhibition to LPC in binding to CD1d.

Lysophosphatidylcholine plays critical role in allergic airway disease manifestation.

Phospholipase A2 (sPLA2), pivotal for allergic and inflammatory response, hydrolyses phosphatidylcholine (PC) to lysophosphatidylcholine (LPC). In present study, the role of LPC in allergic airway disease manifestation was studied using mouse model. Balb/c mice were immunized using cockroach extract (CE) and LPC release was blocked by sPLA2 inhibitor. Airway hyperresponse (AHR), lung-histology, total and differential leukocyte count (TLC&DLC), Th2 type cytokines, sPLA2 activity and LPC levels in bronchoalveolar lavage fluid (BALF) were measured. Exogenous LPC was given to the mice with or without CE sensitization, to demonstrate its role in allergic airway disease manifestation. Anti-CD1d antibody was given to study the involvement of natural killer T (NKT) cells in LPC induced response. AHR, lung-inflammation, TLC, DLC, Th2 type cytokines, sPLA2 activity and LPC levels were increased on CE challenge. sPLA2 activity and LPC release was blocked by sPLA2-inhibitor, which decreased AHR, and inflammatory parameters. Exogenous LPC with or without CE sensitization increased above parameters. CE challenge or LPC exposure increased LY49C(+)TCRß(+) NKT cells in BALF and spleen, which was reduced by anti-CD1d antibody, accompanied with reduction in AHR and allergic airway inflammation parameters. Conclusively, LPC induces allergic airway disease manifestation and it does so probably via CD1d-restricted LY49C(+)TCRß(+) NKT cells.

Gender differences in 7 years trends in cholesterol lipoproteins and lipids in India: Insights from a hospital database.

OBJECTIVE: To determine gender differences and secular trends in total, low-density lipoprotein (LDL) and high DL (HDL) cholesterol and triglycerides using a large hospital database in India. METHODS: All blood lipid tests evaluated from July 2007 to December 2014 were analyzed. Details of gender and age were available. Statin therapy was obtained at two separate periods. Trends were calculated using linear regression and Mantel-Haenszel X(2). RESULTS: Data of 67395 subjects (men 49,904, women 17,491) aged 51 ± 12 years were analyzed. Mean levels (mg/dl) were total cholesterol 174.7 ± 45, LDL cholesterol 110.7 ± 38, non-HDL cholesterol 132.1 ± 44.8, HDL cholesterol 44.1 ± 10, triglycerides 140.8 ± 99, and total: HDL cholesterol 4.44 ± 1.5. Various dyslipidemias in men/women were total cholesterol ≥200 mg/dl 25.4/36.4%, LDL cholesterol ≥130 mg/dl 28.1/35.0% and ≥100 mg/dl 54.4/66.4%, non-HDL cholesterol ≥160 mg/dl 25.5/29.6%, HDL cholesterol <40/50 mg/dl 54.4/64.4%, and triglycerides ≥150 mg/dl 34.0/26.8%. Cholesterol lipoproteins declined over 7 years with greater decline in men versus women for cholesterol (Blinear regression = -0.82 vs. -0.33, LDL cholesterol (-1.01 vs. -0.65), non-HDL cholesterol (-0.88 vs. -0.52), and total: HDL cholesterol (-0.02 vs. -0.01). In men versus women there was greater decline in prevalence of hypercholesterolemia (X(2) trend 74.5 vs. 1.60), LDL cholesterol ≥130 mg/dl (X(2) trend 415.5 vs. 25.0) and ≥100 mg/dl (X(2) trend 501.5 vs. 237.4), non-HDL cholesterol (X(2) trend 77.4 vs. 6.85), total: HDL cholesterol (X(2) trend 212.7 vs. 10.5) and high triglycerides (X(2) trend 10.8 vs. 6.15) (P < 0.01). Use of statins was in 2.6% (36/1405) in 2008 and 9.0% (228/2527) in 2014 (P < 0.01). Statin use was significantly lower in women (5.8%) than men (10.3%). CONCLUSIONS: In a large hospital - database we observed greater hypercholesterolemia and low HDL cholesterol in women. Mean levels and prevalence of high total, LDL, non-HDL and total: HDL cholesterol declined over 7 years. A lower decline was observed in women. This was associated with lower use of statins.

Pancreatic extra-gastrointestinal stromal tumour with documentation of C-kit mutation: a case report.

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal neoplasms located in the alimentary tract. Stromal tumours that arise outside the gastrointestinal tract as primary tumour are designated as extra-gastrointestinal stromal tumours (EGIST). The EGIST are located in mesentry, omentum, retroperitoneum and rarely in pancreas. Only 19 cases of pancreatic EGIST (pEGIST) have been reported in the literature. Of these, there were only two cases of pEGIST with documentation of molecular alteration in C-Kit gene. We here report a third case of primary pEGIST with documentation of C-kit mutation.

Correlation of morphological pattern of optical coherence tomography in diabetic macular edema with systemic risk factors in middle aged males.

To study correlation of different optical coherence tomography (OCT) patterns of diabetic macular edema (DME) with systemic risk factors. Institutional cross-sectional double-masked non-interventional study with 330 eyes of middle-aged male type 2 diabetes patients with DME. Various systemic parameters were measured. Diffuse retinal thickening (DRT), cystoid and serous patterns of DME were identified on OCT. Comparison between DRT versus non-DRT and serous versus non-serous eyes was done in respect to systemic parameters. Correlation of serous and DRT pattern was tested with systemic parameters above and below specified values. Mean age was 54.4 ± 7.1 years. Mean duration of diabetes was 8.7 ± 4.2 years. Mean serum globulin level was significantly higher (p = 0.018) in serous compared to non-serous group. Prevalence of serous DME was significantly high in those with serum globulin level >3.5 gm/dl (prevalence ratio = 3.01, p = 0.040). Significant correlation of central macular thickness was observed with duration of diabetes (p = 0.002, r = 0.440).Visual acuity (logMAR) was correlated significantly with HbA1C (p = 0.031, r = 0.305). Increased serum globulin, a positive phase reactant of inflammation, was found significant independent risk factor for development of serous DME. This study did not identify any modifiable systemic factor for any of the OCT patterns in DME.

Adult hepatic mesenchymal hamartoma: an unusual case.

Mesenchymal hamartoma is a benign hamartomatous lesion with unknown histogenesis. It generally occurs in pediatric population and has been rarely reported in adults. We report an unusual case of a cystic mesenchymal hamartoma of liver in an 81-year-old elderly male. A provisional diagnosis of liver abscess was made and definitive histopathology confirmed the diagnosis. This case has been reported because of its rarity.

Intranasal administration of a combination of choline chloride, vitamin C, and selenium attenuates the allergic effect in a mouse model of airway disease.

Respiratory allergic disease is an inflammatory condition accompanied by oxidative stress. Supplementation of an anti-inflammatory agent with antioxidants may have a therapeutic effect. In this study, the effects of choline chloride in combination with antioxidants were evaluated via the intranasal route in a mouse model of allergic airway disease. Balb/c mice were sensitized on days 0, 7, and 14 and challenged on days 25-30 with cockroach extract (CE) and with a booster challenge on day 38. They were treated with choline chloride (ChCl; 1mg/kg), vitamin C (Vit C; 308.33 mg/kg), and selenium (Se; 1mg/kg) alone or in combination via the intranasal route on days 31, 33, 35, 37, and 39. The mice were sacrificed on day 40 to collect blood, bronchoalveolar lavage fluid, lungs, and spleen. Mice immunized with CE showed a significant increase in airway hyperresponsiveness (AHR), lung inflammation, Th2 cytokines, and the oxidative stress markers intracellular reactive oxygen species and 8-isoprostanes compared to the phosphate-buffered saline control group. A significant decrease was observed in these parameters with all the treatments (p<0.01). The highest decrease was noticed in the ChCl+Vit C+Se-treated group, with AHR decreased to the normal level. This group also showed the highest decrease in airway inflammation (p<0.001), IL-4 and IL-5 (p<0.001), IgE and IgG1 (p<0.001), NF-κB (p<0.001), and 8-isoprostane levels (p<0.001). Glutathione peroxidase activity, which was decreased significantly in CE-immunized mice, was restored to normal levels in this group (p<0.001). IL-10 level was decreased in CE-immunized mice and was restored to normal by combination treatment. The combination treatment induced FOXP3(+) cells in splenocyte culture, responsible for the upregulation of IL-10. In conclusion, the combination of choline chloride, vitamin C, and selenium via the intranasal route reduces AHR, inflammation, and oxidative stress, probably by causing IL-10 production by FOXP3(+) cells, and possesses therapeutic potential against allergic airway disease.

A case of massive broad ligament leiomyoma imitating an ovarian tumour.

Leiomyomas are the most common benign tumours of female reproductive system which occur in women of child- bearing ages. Large fibroids are known to arise from uterus, but rarely from broad ligament. An unusual clinical presentation of a massive, broad ligament fibroid which measured 25 cm x 22 cm x 21 cm, and imitated an ovarian tumour because of its myxoid and cystic degenerations, has been described.

Intracellular Hmgb1 inhibits inflammatory nucleosome release and limits acute pancreatitis in mice.

BACKGROUND & AIMS: High mobility group box 1 (HMGB1) is an abundant protein that regulates chromosome architecture and also functions as a damage-associated molecular pattern molecule. Little is known about its intracellular roles in response to tissue injury or during subsequent local and systemic inflammatory responses. We investigated the function of Hmgb1 in mice after induction of acute pancreatitis. METHODS: We utilized a Cre/LoxP system to create mice with pancreas-specific disruption in Hmbg1 (Pdx1-Cre; HMGB1(flox/flox) mice). Acute pancreatitis was induced in these mice (HMGB1(flox/flox) mice served as controls) after injection of l-arginine or cerulein. Pancreatic tissues and acinar cells were collected and analyzed by histologic, immunoblot, and immunohistochemical analyses. RESULTS: After injection of l-arginine or cerulein, Pdx1-Cre; HMGB1(flox/flox) mice developed acute pancreatitis more rapidly than controls, with increased mortality. Pancreatic tissues of these mice also had higher levels of serum amylase, acinar cell death, leukocyte infiltration, and interstitial edema than controls. Pancreatic tissues and acinar cells collected from the Pdx1-Cre; HMGB1(flox/flox) mice after l-arginine or cerulein injection demonstrated nuclear catastrophe with greater nucleosome release when compared with controls, along with increased phosphorylation/activation of RELA nuclear factor κB, degradation of inhibitor of κB, and phosphorylation of mitogen-activated protein kinase. Inhibitors of reactive oxygen species (N-acetyl-l-cysteine) blocked l-arginine-induced DNA damage, necrosis, apoptosis, release of nucleosomes, and activation of nuclear factor κB in pancreatic tissues and acinar cells from Pdx1-Cre; HMGB1(flox/flox) and control mice. Exogenous genomic DNA and recombinant histone H3 proteins significantly induced release of HMGB1 from mouse macrophages; administration of antibodies against H3 to mice reduced serum levels of HMGB1 and increased survival after l-arginine injection. CONCLUSIONS: In 2 mouse models of acute pancreatitis, intracellular HMGB1 appeared to prevent nuclear catastrophe and release of inflammatory nucleosomes to block inflammation. These findings indicate a role for the innate immune response in tissue damage.

Synthesis and synergistic, additive inhibitory effects of novel spiro derivatives against ringworm infections.

An environmentally benign solvent free synthesis of various spiro-1,4-dihydropyridines (1,4-DHPs) incorporating 2-oxindole/piperidines is performed in 5-8 min with reasonable purity in 80-90% yield under microwave irradiation using montmorillonite KSF as an inorganic solid support. The reaction is found to be general with respect to various cyclic carbonyl compounds, e.g. cyclohexanone, substituted indole-2,3-dione, and piperidinone derivatives. In our study, these compounds were also found effective against dermatophytes and other fungal organisms. Our results suggest that novel spiro derivatives can be used for the treatment of dermatophytosis or ringworm infections.