Risk of renal cell carcinoma and polymorphism in phase I xenobiotic metabolizing CYP1A1 and CYP2D6 enzymes

The progressive increase in sporadic renal cell carcinoma (RCC) observed in industrialized countries supports the opinion that certain carcinogens present in the environment (tobacco smoke, drugs, pollutants, and dietary constituents) may affect the occurrence and progression of this disease in developing countries like India. The polymorphism of the enzymes involved in metabolism of such environmental factors may, therefore, confer variable propensity to RCC. The possible association between RCC and a polymorphism of the CYP1A1 and CYP2D6 genes specific to the Indian population was examined using peripheral blood DNA from 196 RCC cases and 250 population controls with detailed data of clinicopathologic characteristics for the disease. The CYP1A1 (val) “variant” genotype, which contains at least 1 copy of the CYP1A1 variant alleles, was found to be associated with a 2.03-fold [GG ver. AA/AG, unadjusted OR = 2.03; 95%CI = 1.233–3.342; P = 0.005] increase in the risk of RCC. There was also a significant association (p^trend = 0.034) between higher frequency of RCC subjects containing at least of copy of the CYP1A1 (val) “variant” genotype with III or IV Fuhrman's grade. Whereas, the CYP2D6 polymorphism did not show any association with RCC risk [TT ver. CT/CC, unadjusted OR = 95%CI = 1.233–3.342; P = 0.005]. There was a significant association (p^trend = 0.001) between the poor metabolizer CYP2D6 (TT) and progression towards higher pathological stage of RCC. Our data demonstrate for the first time a significant association between pharmacogenetic polymorphisms of CYP1A1 and risk of RCC development in the Indian population. The findings suggest that inter-individual variation in the phase I metabolic enzymes involved in the fictionalization and detoxification of specific xenobiotics is an important susceptibility factor for development and progression of RCC in Indians.     

Changes in sleep architecture after burn injury: ‘Waking up’ to this unaddressed aspect of postburn rehabilitation in the developing world

BACKGROUND:

Changes in sleep architecture are common phenomena observed in post-traumatic patients; such altered sleeping patterns have negative implications on various phases of rehabilitation. Sleep is an essential process, without which one cannot function effectively and, hence, any aberrations in the quality of sleep in such patients need to be critically analyzed.

OBJECTIVE:

To probe the quality of sleep in postburn patients at one year compared with a group of adequately matched controls.

METHODS:

Quality of sleep in postburn patients at one year was measured using the Pittsburg Sleep Quality Index questionnaire and compared with a group of adequately matched controls. Data were tabulated and subjected to statistical analysis using Pearson’s χ² test.

RESULTS:

The relationship between the postburn state and sleep disturbances was found to be statistically significant. Other relevant parameters are also highlighted and discussed.

DISCUSSION:

Sleep is one of aspect of functioning that may be least taken into account by professionals during the phase of postburn rehabilitation because more obvious threats receive preferred treatment. Unless these problems are dealt with in the postburn period, rehabilitation can never be complete.

CONCLUSION:

Postburn patients experience significant changes in sleep architecture, which need to be taken into account to enable complete rehabilitation of the patient.     

The mental health of children affected by armed conflict: Protective processes and pathways to resilience

This paper examines the concept of resilience in the context of children affected by armed conflict. Resilience has been frequently viewed as a unique quality of certain ‘invulnerable’ children. In contrast, this paper argues that a number of protective processes contribute to resilient mental health outcomes in children when considered through the lens of the child's social ecology. While available research has made important contributions to understanding risk factors for negative mental health consequences of war-related violence and loss, the focus on trauma alone has resulted in inadequate attention to factors associated with resilient mental health outcomes. This paper presents key studies in the literature that address the interplay between risk and protective processes in the mental health of war-affected children from an ecological, developmental perspective. It suggests that further research on war-affected children should pay particular attention to coping and meaning making at the individual level; the role of attachment relationships, caregiver health, resources and connection in the family, and social support available in peer and extended social networks. Cultural and community influences such as attitudes towards mental health and healing as well as the meaning given to the experience of war itself are also important aspects of the larger social ecology.     

Ocular toxocariasis in a child: a case report from Kashmir, north India

Toxocariasis is an important zoonotic disease caused by the second stage larva of Toxocara canis or Toxocara cati . The typical clinical syndromes of toxocariasis in humans are visceral and ocular toxocariasis. Ocular toxocariasis may presents as peripheral inflammatory mass, posterior pole granuloma and endophthalmitis. We report a serologically confirmed case of ocular toxocariasis in 12-year-old female. The diagnosis was confirmed by detection of anti- Toxocara antibodies in aqueous and vitreous sample by enzyme-linked immunosorbent assay. We suggest that ophthalmologist in this region should include ocular toxocariasis in differential diagnosis particularly in children and young adults.     

Cognitive impairment in rapid‐onset dystonia‐parkinsonism

Rapid‐onset dystonia‐parkinsonism (RDP) is caused by mutations in the ATP1A3 gene. This observational study sought to determine if cognitive performance is decreased in patients with RDP compared with mutation‐negative controls. We studied 22 familial RDP patients, 3 non‐motor‐manifesting mutation‐positive family members, 29 mutation‐negative family member controls in 9 families, and 4 unrelated RDP patients, totaling 58 individuals. We administered a movement disorder assessment, including the Burke‐Fahn‐Marsden Dystonia Rating Scale (BFMDRS) and the Unified Parkinson's Disease Rating Scale (UPDRS) and a cognitive battery of memory and learning, psychomotor speed, attention, and executive function. The cognitive battery was designed to evaluate a wide range of functions; recognition memory instruments were selected to be relatively pure measures of delayed memory, devoid of significant motor or vocal production limitations. Comparisons of standardized cognitive scores were assessed both with and without controlling for psychomotor speed and similarly for severity of depressive symptoms. A majority of RDP patients had onset of motor symptoms by age 25 and had initial symptom presentation in the upper body (face, mouth, or arm). Among patients, the BFMDRS (mean ± SD, 52.1 ± 29.5) and UPDRS motor subscore (29.8 ± 12.7) confirmed dystonia‐parkinsonism. The affected RDP patients performed more poorly, on average, than mutation‐negative controls for all memory and learning, psychomotor speed, attention, and executive function scores (all P ≤ 0.01). These differences persisted after controlling for psychomotor speed and severity of depressive symptoms. Impaired cognitive function may be a manifestation of ATP1A3 mutation and RDP. © 2014 International Parkinson and Movement Disorder Society     

Regional brain imaging of vesicular acetylcholine transporter using o‐[125I]iodo‐trans‐decalinvesamicol as a new potential imaging probe

In this study, the regional rat brain distribution of radioiodinated o‐iodo‐trans‐decalinvesamicol ([¹²⁵I]OIDV) was determined in vivo to evaluate its potential as a single‐photon emission computed tomography (SPECT) imaging probe for vesicular acetylcholine transporter (VAChT). Following intravenous injection, [¹²⁵I]OIDV passed freely across the blood–brain barrier and accumulated in rat brain. The accumulation of [¹²⁵I]OIDV in rat brain was significantly reduced by coadministration of (+/?)‐vesamicol (0.125 µmol). In contrast, the coadministration of σ‐receptor ligands, such as (+)‐pentazocine (0.125 µmol) as a σ‐1 receptor ligand and (+)?3‐(3‐hydroxyphenyl)‐N‐propylpiperidine (0.125 µmol) as a σ‐1 and σ‐2 receptor ligands, barely affected the accumulation of [¹²⁵I]OIDV in rat brain. These findings in vivo were corroborated by autoradiographic analysis ex vivo. The authors found that the tracer binds with pharmacological selectivity to VAChT in rat brain and predicted that it may likewise serve in translational SPECT imaging studies of this marker in the integrity of cholinergic innervations. Synapse 68:107–113, 2014. © 2013 Wiley Periodicals, Inc.