Organ distribution and biological compatibility of surface-functionalized reduced graphene oxide.

Graphene is an sp2 hybridized allotrope of carbon with a honeycomb lattice structure that has many applications in biomedicine owing to its unique physico-chemical properties. Graphene has attracted much interest from scientists for its biomedical potential, including in drug/gene delivery, fluorescent labeling of target analytes, tissue engineering, regenerative medicine and MRI contrast enhancement. However, there are very limited data available concerning the toxicity of graphene, and efforts have been made to study the bio-nano interactions of Pluronic functionalized reduced graphene oxide (rGO-P) in animal models. The present study aimed to evaluate the systemic toxicity of rGO-P and its ability to cross the blood-brain barrier in Swiss Albino mice subject to acute exposure to 10 mg kg-1 body weight of rGO-P. Prolonged exposure was evaluated in female Wistar rats by analyzing feto-placental transmission and any associated developmental neurotoxicity after intravenous administration of 5 mg kg-1 and 10 mg kg-1 body weight of rGO-P. Biodistribution analysis using confocal Raman mapping indicated that tiny amounts of rGO-P accumulated in major organs of both dams and pups, with no evident toxic response. The accumulation of rGO-P in various tissues of rat pups born to treated dams is ample evidence of feto-placental transmission. The present study clearly suggests that rGO-P is not toxic under any of the experimental conditions. These findings can therefore be carried forward for application of rGO-P in drug/gene delivery, early diagnosis and treatment of various diseases in neonates and adults. The results of the study show that rGO-P is an auspicious and promising material for future healthcare applications.

Green synthesis of Pluronic stabilized reduced graphene oxide: Chemical and biological characterization.

The wonder material graphene has numerous potential applications in nanoelectronics, biomedicine, storage devices, etc. Synthesis of graphene is highly challenging due to the toxic chemicals used and its low yield. In the present study, a facile green route for synthesis of reduced graphene oxide (rGO) was carried out using ascorbic acid as reducing agent. rGO was stabilized using Pluronic P123 polymer to give Pluronic stabilized reduced graphene oxide (rGO-P) and gave superior yield (15 mg graphene oxide yielded ˜13 mg rGO-P). Despite the potential neuroscience applications of graphene, the impending toxicological outcome upon interaction with neurons is not well understood. Here, differentiated PC-12 neuron-like cells exposed to rGO-P showed a dose-dependent cytotoxicity. Membrane disruption and cytoskeletal integrity remained uncompromised after 24 h exposure. Oxidative stress in PC-12 was evident due to an increase in ROS generation in dose and time-dependent manner. In vivo acute toxicity was assessed in mice administered with 10 mg/kg body weight of rGO-P. There were no evident changes in behaviour, motor function or other morphological changes. In conclusion, rGO-P was successfully synthesized and provided superior yield. Even though in vitro toxicity testing showed dose-dependent toxicity, in vivo toxic effect was not apparent.

Polymorphism in factor VII gene modifies phenotype of severe haemophilia.

The basis for 10-15% of patients with severe haemophilia having clinically mild disease is not fully understood. We hypothesized that polymorphisms in various coagulant factors may affect frequency of bleeding while functionally significant polymorphisms in inflammatory and immunoregulatory genes may also contribute to variations in the extent of joint damage. These variables were studied in patients with severe haemophilia, who were categorized as 'mild' (<5 bleeds in the preceding year, <10 World Federation of Haemophilia clinical and <10 Pettersson scores, n = 14) or 'severe' (all others, n = 100). A total of 53 parameters were studied in each individual for their association with the clinical severity. Age, F8:c activity and the incidence of thrombotic markers were comparable between the groups while the median number of bleeds, number of affected joints, clinical, radiological and functional joint scores (P < or = 0.001) and life-time clotting factor use (P < or = 0.007) were different. Patients with severe molecular defects had a 4.1-fold increased risk for a severe phenotype (95% CI: 1.18-14.42, P = 0.026) compared with other mutations. Of the polymorphisms studied, the FVII353Q (RR = 3.5, 95% CI: 1.04-12.05, P = 0.044) allele was associated with a severe phenotype. This data shows that apart from the F8/F9 genotype, functional polymorphisms in FVII gene affect the phenotype of patients with severe haemophilia.

The "dot-in-circle" sign -- a characteristic MRI finding in mycetoma foot: a report of three cases.

Three patients referred for MRI of the foot were found to have imaging features characteristic of mycetoma. Two patients presented with recurrent soft tissue masses, which were operated on several times and not suspected to be of infective aetiology. The third patient had typical clinical features with a history of blackish granule discharge. In all three patients, MRI showed conglomerate areas of small round discrete T(2) weighted hyperintense lesions, representing granulation tissue surrounded by a low-signal-intensity rim representing intervening fibrous septa. Within many of these hyperintense lesions, there was a central low-signal-intensity dot, which gives rise to the "dot-in-circle" sign that has been very rarely described in the literature. This sign is an easily recognisable and unique appearance that is highly suggestive of mycetoma.

Is pneumorrhachis a poor prognostic sign in acute gangrenous abdominal emergencies?

Pneumorrhachis (air in the spinal canal) is an uncommon radiological finding. Its detection in gangrenous abdominal emergencies is rarer with uncertain prognostic significance. We illustrate the computed tomography features and assess the patient outcomes in two cases of pneumorrhachis identified in gangrenous pathologies of the abdomen (emphysematous pyelonephritis and bowel gangrene). Patient outcome was poor in the current and previously reported cases. Pneumorrhachis could be an additional imaging sign of poor prognosis in acute gangrenous abdominal emergencies.

Psychometric analysis of the Functional Independence Score in Haemophilia (FISH).

Joint morbidity in haemophilia has traditionally been measured using clinical and radiological scores. There have been no reliable, validated tools for the assessment of functional independence in persons with haemophilia till recently. The Functional Independence Score in Haemophilia (FISH) has been developed as a performance based assessment tool to address this need. The FISH is designed to measure the patient's independence in performing activities of daily living (grooming and eating, bathing and dressing), transfers (chair and floor), and mobility (walking, step climbing and running). On assessment of its psychometric properties in 63 patients with haemophilia (mean age 14 years), FISH was found to have good internal consistency (Cronbach's alpha of 0.85). It had moderate correlation with the World Federation of Hemophilia clinical score (r = -0.61), and a correlation with the Pettersson score of -0.38. It had good correlation with other self-rated functional scores, such as the Stanford Health Assessment Questionnaire (r = -0.75); the Western Ontario and McMaster Universities Osteoarthritis Index (r = -0.66) and the Haemophilia Activities List (HAL) (r = -0.66). It had good reliability with a pooled intra class correlation of 0.98. On assessing responsiveness following treatment of flexion deformities of the knee in 12 patients, the FISH showed significant changes in the score with a standardized responsiveness mean of -1.93. In conclusion, the FISH was found to be a reliable and valid tool with good internal consistency and responsiveness to therapy, for the assessment of functional independence in persons with haemophilia.

Unusual extra-axial central nervous system involvement of non-Hodgkin's lymphoma: magnetic resonance imaging.

The MR imaging findings in a patient with non-Hodgkin's lymphoma with unusual involvement of the sella, pituitary stalk and left parasellar region are reported here. On the basis of the MR imaging findings, the initial differential diagnosis included invasive pituitary adenoma, a granulomatous lesion and en plaque meningioma. Trans-sphenoidal biopsy of the sellar mass showed chronic inflammatory changes and the patient was initially treated for tuberculosis. Because follow-up imaging showed the lesion to be progressive, a biopsy was done of an enlarged right inguinal lymph node. This revealed non-Hodgkin's lymphoma.