An update on cancer- and chemotherapy-related cognitive dysfunction: current status

The purpose of this review is to summarize the current literature on the effects of cancer treatment-related cognitive difficulties, with a focus on the effects of chemotherapy. Numerous patients have cognitive difficulties during and after cancer treatments and, for some, these effects last years after treatment. We do not yet fully understand which factors increase susceptibility to cognitive difficulties during treatment and which cause persistent problems. We review possible contributors, including genetic and biological factors. Mostly we focus is on cognitive effects of adjuvant chemotherapy for breast cancer; however, cognitive effects of chemotherapy on the elderly and brain tumor patients are also discussed.     

Pharmacologic treatment of cancer-related fatigue

Fatigue is the most commonly reported symptom in patients with cancer, with a prevalence of over 60% reported in the majority of studies. This paper systematically reviews pharmacologic agents in the treatment of cancer-related fatigue (CRF). We conducted a literature review of clinical trials that assessed pharmacologic agents for the treatment of CRF. These agents include hematopoietics (for anemia), corticosteroids, and psychostimulants. Other therapeutic agents that are less well studied for CRF but are currently the focus of clinical trials include l-carnitine, modafinil, bupropion, and selective serotonin reuptake inhibitors such as paroxetine. Disclosure of potential conflicts of interest is found at the end of this article.     

Assessment of cancer-related fatigue: implications for clinical diagnosis and treatment

Cancer-related fatigue (CRF) is a highly prevalent and debilitating symptom experienced by most cancer patients during, and often for considerable periods after, treatment. The recognition of the importance of CRF to patients' psychosocial and cognitive functioning, as well as to their quality of life, has driven the development of a wide range of assessment tools for screening and diagnosis of CRF. Over 20 different measures have been used to assess CRF from either a unidimensional or multi-dimensional perspective. Unidimensional measures are often single-question scales that generally focus on identifying the occurrence and severity of CRF, whereas multidimensional measures may also examine the effect of CRF across several domains of physical, socio-emotional, and cognitive functioning. This paper provides an overview and critique of measures commonly used to assess CRF. Single-question assessment is the most commonly used and the most useful methodology. Strategies to facilitate reliable assessment of CRF are also discussed. Disclosure of potential conflicts of interest is found at the end of this article.     

Norrie Disease: First Mutation Report and Prenatal Diagnosis in an Indian Family

Norrie Disease (ND) is a rare X-linked recessive disorder characterised by congenital blindness due to severe retinal dysgenesis. Hearing loss and intellectual disability is present in 30–50?% cases. ND is caused by mutations in the NDP gene, located at Xp11.3. The authors describe mutation analysis of a proband with ND and subsequently prenatal diagnosis. Sequence analysis of the NDP gene revealed a hemizygous missense mutation arginine to serine in codon 41 (p.Arg41Ser) in the affected child. Mother was carrier for the mutation. In a subsequent di-chorionic di-amniotic pregnancy, the authors performed prenatal diagnosis by mutation analysis on chorionic villi sample at 11?wk of gestation. The fetuses were unaffected. This is a first mutation report and prenatal diagnosis of a familial case of Norrie disease from India. The importance of genetic testing of Norrie disease for confirmation, carrier testing, prenatal diagnosis and genetic counseling is emphasized.     

Generation of diagnostic anti-teliospore antibodies for development of specific immunodiagnostic format for detection of Karnal bunt (Tilletia indica) of wheat

Rabbit antisera were generated against four preparations of teliospores of Tilletia indica the fungus responsible for Karnal bunt in wheat having titre ranging from 1:2500 to 1:10,000. The suitability of four solubilising agents (I–IV) used for extraction of teliospores/spore proteins was assessed, highest protein extractability was observed with solubilising agent I (0.5% sodium dodecyl sulphate). The maximum immunoreactivity in enzyme linked immunosorbent assay (ELISA) was observed with the teliosporic protein(s) extracted using solubilising agent I followed by agent II, IV and III. Further, the results of western blotting with proteins from different fungal pathogens using anti-intact teliospores antibody showed one unique immunoreactive band of 28 kDa with teliosporic protein of T. indica only. The potential diagnostic antibody was generated against the characterised protein (28 kDa) of teliospore wall's antigen of T. indica. The developed diagnostic antibody and solubilising agent I could therefore be employed for development of specific and rapid immunodiagnostic format for detection of Karnal bunt.     

Overview of dynamic contrast-enhanced MRI in prostate cancer diagnosis and management

OBJECTIVE: This article is a primer on the technical aspects of performing a high-quality dynamic contrast-enhanced MRI (DCE-MRI) examination of the prostate gland. CONCLUSION: DCE-MRI is emerging as a useful clinical technique as part of a multi-parametric approach for evaluating the extent of primary and recurrent prostate cancer. Performing a high-quality DCE-MRI examination requires a good understanding of the technical aspects and limitations of image acquisition and postprocessing techniques.     

Curcumin Nanoparticles Attenuate Neurochemical and Neurobehavioral Deficits in Experimental Model of Huntington’s Disease

Till date, an exact causative pathway responsible for neurodegeneration in Huntington’s disease (HD) remains elusive; however, mitochondrial dysfunction appears to play an important role in HD pathogenesis. Therefore, strategies to attenuate mitochondrial impairments could provide a potential therapeutic intervention. In the present study, we used curcumin encapsulated solid lipid nanoparticles (C-SLNs) to ameliorate 3-nitropropionic acid (3-NP)-induced HD in rats. Results of MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay and succinate dehydrogenase (SDH) staining of striatum revealed a marked decrease in Complex II activity. However, C-SLN-treated animals showed significant increase in the activity of mitochondrial complexes and cytochrome levels. C-SLNs also restored the glutathione levels and superoxide dismutase activity. Moreover, significant reduction in mitochondrial swelling, lipid peroxidation, protein carbonyls and reactive oxygen species was observed in rats treated with C-SLNs. Quantitative PCR and Western blot results revealed the activation of nuclear factor-erythroid 2 antioxidant pathway after C-SLNs administration in 3-NP-treated animals. In addition, C-SLN-treated rats showed significant improvement in neuromotor coordination when compared with 3-NP-treated rats. Thus, the results of this study suggest that C-SLNs administration might be a promising therapeutic intervention to ameliorate mitochondrial dysfunctions in HD.     

Preserved umbilical cord facilitates antenatal diagnosis of spinal muscular atrophy

Spinal Muscular atrophy (SMA) Type I is a fatal autosomal recessive disease caused by homozygous deletion of telometric region of exon 7/8 of the SMN gene. Prenatal diagnosis is feasible and desirable by most families. We report on prenatal diagnosis of SMAI in a family where dried umbilical cord stump from the deceased affected baby was used to confirm the diagnosis. Prenatal diagnosis was provided in the subsequent pregnancy. We emphasize the need for storing DNA from individuals affected with suspected single gene disorders.     

Carrier frequency of F508del mutation of cystic fibrosis in Indian population.

BACKGROUND: Cystic fibrosis (CF) is considered to be very rare in Indian subcontinent. Based on reports of CF in migrants from Indian subcontinent to United Kingdom and United States of America, the prevalence of CF is estimated to be between 1/10,000 and 1/40,000 in this ethnic group. The present study was done to estimate the carrier frequency of F508del mutation among neonates using cord blood samples to reflect the prevalence of CF in the study population. METHODS: 955 mothers delivering at our hospital between December 1999 and November 2000 were enrolled. Cord blood samples were analyzed for F508del mutation using polymerase chain reaction and gel electrophoresis. The frequency of patients homozygous for F508del mutation in the population was estimated using Hardy-Weinberg principle. The prevalence of CF was estimated by using the proportion of F508del homozygous cases out of all CF patients, as reported in various studies (19-44%) from Indian subcontinent. RESULTS: Out of 955 cord blood samples, 4 were positive for F508del mutation. The carrier frequency and gene frequency of F508del mutation in the Indian population was calculated to be 1/238 (0.42%) and 1/477 (0.21%), respectively. Frequency of CF patients homozygous for F508del mutation is 1/228,006. The estimated prevalence of CF is 1/43,321 to 1/100,323 in Indian population. CONCLUSION: CF does occur in Indian subcontinent though the prevalence is lesser than the Caucasian population.     

Surface Plasmon Resonance Sensogram Based Characterization of Antibodies Raised Against Intact Teliospores and Purified Diagnostic Antigen for Development of Nano-Immunosensor for Fungal Spore Antigen of Karnal Bunt (Tilletia indica) of Wheat

The label free real time surface plasmon resonance based immuno-sensing system was first time demonstrated in the authors’ lab using a mercaptoundecanoic acid modified gold sensor chip. The kinetics of the antigen–antibody interaction was determined for optimization of resonance signal intensity for the detection of antigen(s) of fungal teliospores-causative entities of Karnal bunt disease of wheat incited by Tilletia indica. The approach involves the use of a rabbit polyclonal (anti-teliospore) antibody and mono-specific antibody generated against intact teliospores and purified diagnostic antigen of 28 kDa protein. The sensitivity of each of these two immunosensors constructed with the different concentrations of teliosporic antigen was determined by sensogram analysis which showed detection sensitivity as low as 625 and 156 pg which is equivalent to 2.5 and 1.0 teliospores over the sensor surface by getting an angle of dip indicating greater affinity of raised anti-teliospore antibodies and monospecific antibody respectively. By using kinetic evaluation software, the equilibrium constant (KD) and maximum binding capacity of analyte (B_max) values were calculated and found to be 3.45 and 331.8 nM respectively using polyclonal and 1.57 and 289.57 nM respectively using monospecific antibody.