Liposomal nanomedicine for breast cancer therapy

Liposomes are well-established nanocarriers for improving the therapeutic index of anticancer agents. A remarkable understanding in the pathophysiology of breast cancer progression has emerged with information on the involved specific biomolecules, which may serve as molecular targets for its therapy. Hormonal and nonhormonal receptors can both be exploited for targeting to breast cancer cells. Targeted delivery of cytotoxic drugs using liposomes is a novel approach for breast cancer therapy. In the present article, we summarize molecular targets present on the breast cancer cells. Recent developments in liposome-based delivery of bioactives for selective treatments of breast cancer are discussed. In addition, utilization of bioenvironmental conditions of tumor for liposome-based targeted delivery is also summed up.     

Current spectrum of malabsorption syndrome in adults in India

Aim  

Tropical sprue was considered to be the most important cause of malabsorption in adults in India. However, several reports indicate that celiac disease is now recognized more frequently.     

Clostridium difficile associated diarrhea: new rules for an old game

C. difficile associated diarrhea (CDAD) is now considered to be one of the commonest causes of nosocomial diarrhea. CDAD, once considered to be a "nuisance" disease, has lately become a "killer" disease with appearance of a hypervirulent strain, toxinotype III. Although the incidence and severity of CDAD have increased in the western world especially in health care settings; it still is under-recognized in India and Asia. Any episode of diarrhea with fever and leucocytosis in a patient on some antibiotics in a health care setting is strong pointer towards presence of CDAD. Clinical suspicion is usually confirmed by ELISA based C. difficile toxin assays in the stool sample. The aim of therapy is to restore normal colonic microflora, resulting in the elimination of C. difficile. Treatment of C.difficile needs to be individualized depending on the severity of the disease and patient characteristics. Majority of patients will require antibiotic therapy and, whenever possible, discontinuation of the predisposing antibiotics. Metronidazole and vancomycin are the mainstay of the treatment of CDAD, as both these agents are highly active against all strains of pathogenic C.difficile. Neither of these drugs is however effective for the carrier state of C. difficile. Approximately 15%-30% of patients experience a symptomatic recurrence after discontinuation of antibiotics. Control of health care associated CDAD involves a range of primarily preventive measures including proper hand hygiene, use of personal protective equipment, environmental decontamination, isolation or cohort nursing and adequate treatment of CDAD cases.     

Abnormalities in metabolic pathways in celiac disease investigated by the metabolic profiling of small intestinal mucosa,blood plasma and urine by NMR spectroscopy

Celiac disease (CeD) is an autoimmune enteropathy caused by gluten intake in genetically predisposed individuals. We investigated the metabolism of CeD by metabolic profiling of intestinal mucosa, blood plasma and urine using NMR spectroscopy and multivariate analysis. The metabolic profile of the small intestinal mucosa was compared between patients with CeD (n = 64) and disease controls (DCs, n = 30). The blood plasma and urinary metabolomes of CeD patients were compared with healthy controls (HCs, n = 39). Twelve metabolites (proline (Pro), arginine (Arg), glycine (Gly), histidine (His), glutamate (Glu), aspartate, tryptophan (Trp), fumarate, formate, succinate (Succ), glycerophosphocholine (GPC) and allantoin (Alln)) of intestinal mucosa differentiated CeD from controls. The metabolome of blood plasma with 18 metabolites (Pro, Arg, Gly, alanine, Glu, glutamine, glucose (Glc), lactate (Lac), acetate (Ace), acetoacetate (AcAc), β‐hydroxybutyrate (β‐OHB), pyruvate (Pyr), Succ, citrate (Cit), choline (Cho), creatine (Cr), phosphocreatine (PCr) and creatinine) and 9 metabolites of urine (Pro, Trp, β‐OHB, Pyr, Succ, N‐methylnicotinamide (NMN), aminohippurate (AHA), indoxyl sulfate (IS) and Alln) distinguished CeD from HCs. Our data demonstrated changes in nine metabolic pathways. The altered metabolites were associated with increased oxidative stress (Alln), impaired healing and repair mechanisms (Pro, Arg), compromised anti‐inflammatory and cytoprotective processes (Gly, His, NMN), altered energy metabolism (Glc, Lac, β‐OHB, Ace, AcAc, Pyr, Succ, Cit, Cho, Cr and PCr), impaired membrane metabolism (GPC and Cho) and intestinal dysbiosis (AHA and IS). An orthogonal partial least square discriminant analysis model provided clear differentiation between patients with CeD and controls in all three specimens. A classification model built by combining the distinguishing metabolites of blood plasma and urine samples gave an AUC of 0.99 with 97.7% sensitivity, 93.3% specificity and a predictive accuracy of 95.1%, which was higher than for the models built separately using small intestinal mucosa, blood plasma and urine. In conclusion, a panel of metabolic biomarkers in intestinal biopsies, plasma and urine samples has potential to differentiate CeD from controls and may complement traditional tests to improve the diagnosis of CeD.     

Staging,Treatment, and Future Approaches of Gallbladder Carcinoma

Background

Gallbladder cancer is the most common malignant cancer of the bile ducts and third most common gastrointestinal malignant in the world for public health. Its relatively low incidence and confused symptoms result in advanced disease at the time of presentation, contributing to poor prognosis and reduced survival associated with this disease. The main function of the gallbladder is to store excreted bile acids from the liver in preparation for a meal. Its main risk factor is prolonged exposure to biliary calculations, although bacterial infections and other inflammatory conditions are associated. Chronic inflammatory bowel conditions are associated with gallbladder cancer. T stage translates to identifying residual disease at reoperation for incidental gallbladder cancer and residual disease negatively affects survival.

Conclusion

It is the most common cancer of gallbladder, gallbladder cancer remains a rare disease. Gallbladder cancer is a rare disease that can be accidentally diagnosed after cholecystectomy or accidentally, often with more advanced disease. The prognosis is generally extremely poor and improvements in surgical resection of this approach have to be re-evaluated, while the role of chemotherapy and radiotherapy remains controversial.

     

Sport concussion assessment tool—Third edition normative reference values for professional Rugby Union players

Objectives

To establish normative reference data for the SCAT3 in professional Rugby Union players.

Pathogenesis of Enteropathy-Associated T Cell Lymphoma

Purpose of Review

To provide an update on the pathogenesis of enteropathy-associated T cell lymphoma (EATL) and its relationship with refractory celiac disease (RCD), in light of current knowledge of immune, genetic, and environmental factors that promote neoplastic transformation of intraepithelial lymphocytes (IELs).

Recent Findings

EATL frequently evolves from RCD type II (RCD II) but can occur “de novo” in individuals with celiac disease. Recurrent activating mutations in members of the JAK/STAT pathway have been recently described in EATL and RCD II, which suggests deregulation of cytokine signaling to be an early event in lymphomagenesis. Intraepithelial T cells are presumed to be the cell of origin of EATL (and RCD II). Recent in vitro molecular and phenotypic analyses and in vivo murine studies, however, suggest an origin of RCD II from innate IELs (NK/T cell precursors), which could also be the cell of origin of RCD II-derived EATL.

Summary

The immune microenvironment of the small intestinal mucosa in celiac disease fosters the development of EATL, often in a multistep pathway.