Protective effect of cholecalciferol against cobalt-induced neurotoxicity in rats: ZO-1/iFABP, ChAT/AchE and antioxidant pathways as potential therapeutic targets.

Cobalt (Co) toxicity has been reported to produce central nervous system and gastrointestinal abnormalities. This study assessed the therapeutic effect of cholecalciferol (Cho) supplementation against damages caused by sub-acute (14-day) cobalt chloride (CoCl2) exposure in the brain and intestines. Thirty-five male Wistar rats were divided equally into five groups: Group I (control) received no treatment; Group II received oral CoCl2 (100 mg/kg) only; Groups III, IV, and V received 1000, 3000 and 6000 IU/kg of cholecalciferol, respectively by oral gavage, and concurrently with CoCl2. Cobalt-treated rats showed neuronal vacuolation and presence of pyknotic nuclei in the cerebral cortex and hippocampus, depletion of Purkinje cells in the cerebellum, as well as inflammation and congestion in the intestinal mucosa. Cobalt also increased brain and intestinal hydrogen peroxide (H2O2) and malondialdehyde (MDA) concentrations, while simultaneously reducing glutathione (GSH) content, superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities. Further, CoCl2 induced increases in brain acetylcholinesterase (AchE) activity and serum zonulin (ZO-1) levels. Conversely, Cho administration suppressed CoCl2-induced damages in the brain and intestines by reducing lipid peroxidation and increasing the activities of antioxidant enzymes. Remarkably, Cho produced stimulation of brain choline acetyltransferase (ChAT) and suppression of AchE activity, along with dose-dependent reduction in serum levels of ZO-1, intestinal fatty acid-binding protein (iFABP) and nitric oxide. In conclusion, the protective role of cholecalciferol against cobalt-induced toxicity occurred via modulation of cholinergic, intestinal permeability and antioxidant pathways. The results may prove significant in the context of the role of gut-brain connections in neuroprotection.

Idiopathic normal pressure hydrocephalus: correlating magnetic resonance imaging biomarkers with clinical response.

Idiopathic Normal Pressure Hydrocephalus (NPH) is a debilitating condition of the elderly. The patient is typically "wet, wobbly and wonky", to different degrees of the triad. The diagnosis is supported by the radiologic finding of dilated ventricles, determined by an elevated Evan's Index (EI) without a demonstrable cause. Patients with newly diagnosed NPH typically respond to ventriculo-peritoneal shunting (VPS). NPH-related dementia is possibly the only surgically reversible dementia. An elevated cerebrospinal fluid (CSF) fl ow rate (FR) is associated with a positive response to shunting. However, post-shunting EI and FRs are unpredictable. Of late, intracranial apparent diffusion coefficient (ADC) quantification via Diffusion Weighted Imaging (DWI) has been emerging as a possible marker in NPH diagnosis. A local study, conducted on a national level, to study the relationship of EI, FR and ADC to pre- and post-shunt clinical measurements has just ended. This review seeks to reconcile the current thinking of NPH, magnetic resonance imaging (MRI) quantification and clinical evaluation, and in the process shed some light on major pathophysiological determinants of the disease.

Value of quantitative MRI biomarkers (Evans' index, aqueductal flow rate, and apparent diffusion coefficient) in idiopathic normal pressure hydrocephalus.

PURPOSE: To define the value of Evans' index (EI), aqueductal flow rate (FR), and apparent diffusion coefficient (ADC) in the diagnosis of normal pressure hydrocephalus (NPH) and to assess the ability of these markers preoperatively to predict shunt response. To shed some light as to the mechanisms responsible for the symptoms of NPH. MATERIALS AND METHODS: Preoperative EI, FR, and ADC readings in nine cases of clinically diagnosed NPH were compared with those of age- and gender-matched controls. Similar pre- and postoperative readings of responders and nonresponders were subsequently compared. RESULTS: Compared with the controls, all measurements were statistically significant except for peak systolic flow rate (pSfr), which was near statistical significance. Comparison of pre- and postoperative readings of responders and nonresponders revealed a decrease in ADC in all responders (P = 0.032). Subdural hemorrhage was found in all nonresponders (P = 0.012). CONCLUSION: For patients presenting with signs and symptoms of NPH, readings on MRI greater than 0.3, 10 mL/min, -9.0 mL/min, and 10.65 x 10(-4) mm(2)/s for EI, peak diastolic flow rate (pDfr), pSfr, and ADC, respectively, add further weight to the diagnosis. The strong correlation between shunt response and ADC decline support our hypothesis that water accumulation in the cerebrum is the major cause for the symptoms of NPH. The presence of subdural hemorrhage in all nonresponders raises suspicion of decreased compliance as the other major cause.

Idiopathic normal pressure hydrocephalus: correlating magnetic resonance imaging biomarkers with clinical response

Idiopathic Normal Pressure Hydrocephalus (NPH) is a debilitating condition of the elderly. The patient is typically "wet, wobbly and wonky", to different degrees of the triad. The diagnosis is supported by the radiologic finding of dilated ventricles, determined by an elevated Evan's Index (EI) without a demonstrable cause. Patients with newly diagnosed NPH typically respond to ventriculo-peritoneal shunting (VPS). NPH-related dementia is possibly the only surgically reversible dementia. An elevated cerebrospinal fluid (CSF) fl ow rate (FR) is associated with a positive response to shunting. However, post-shunting EI and FRs are unpredictable. Of late, intracranial apparent diffusion coefficient (ADC) quantification via Diffusion Weighted Imaging (DWI) has been emerging as a possible marker in NPH diagnosis. A local study, conducted on a national level, to study the relationship of EI, FR and ADC to pre- and post-shunt clinical measurements has just ended. This review seeks to reconcile the current thinking of NPH, magnetic resonance imaging (MRI) quantification and clinical evaluation, and in the process shed some light on major pathophysiological determinants of the disease.

Teleradiology in Singapore--taking stock and looking ahead.

Teleradiology will have a significant impact on the delivery of healthcare and the practice of medicine. In order to ensure a positive outcome, the expected benefits, limitations and potential pitfalls of teleradiology must be carefully considered. For Singapore, teleradiology can be used to facilitate a quantum leap in the standards of radiological services. This can be achieved through the development of an integrated, nationwide, high-speed radiology network which will allow patients to have access to high-quality and responsive subspecialty radiology expertise located throughout the country. If judiciously implemented, teleradiology has the potential to propel Singapore radiology to an unprecedented level of professional quality and service delivery, and will provide the framework for sustainable radiological insourcing from other countries.

Teleradiology in Singapore--taking stock and looking ahead

Teleradiology will have a significant impact on the delivery of healthcare and the practice of medicine. In order to ensure a positive outcome, the expected benefits, limitations and potential pitfalls of teleradiology must be carefully considered. For Singapore, teleradiology can be used to facilitate a quantum leap in the standards of radiological services. This can be achieved through the development of an integrated, nationwide, high-speed radiology network which will allow patients to have access to high-quality and responsive subspecialty radiology expertise located throughout the country. If judiciously implemented, teleradiology has the potential to propel Singapore radiology to an unprecedented level of professional quality and service delivery, and will provide the framework for sustainable radiological insourcing from other countries.

Phonological processing in Chinese-English bilingual biscriptals: an fMRI study.

Different activation loci have been reported for language processing in unilingual Chinese and unilingual English participants, as well as in bilingual readers of English and French, two alphabetic languages. Nevertheless, the extant imaging work on Mandarin-English bilinguals favors common neural substrates for English and Chinese, languages with contrasting oral and written forms. We investigated the phonological processes in reading for English-Chinese biscriptals using a homophone matching task with parallel behavioral (n = 28) and fMRI (n = 6) experiments. Unlike previous reports, we observed distinct regions of activation for Mandarin in the left and right frontal lobes, the left temporal lobe, and the right occipital lobe, plus distinct regions of activation for English bilaterally in both the frontal and parietal lobes. The implications of these novel findings are discussed with reference to language representation in bilinguals.

Combined treatment with BCG and chemotherapy for metastatic gastrointestinal cancer.

The survival of patients who have cancers of the gastrointestinal tract is poor even after surgical resection of all gross disease. In an initial consecutive series of patients with metastatic or recurrent cancers, an attempt to improve survival with combined nonspecific immunostimulation by the intraperitoneal administration of BCG followed by oral BCG cycled with chemotherapy was studied. The results suggested that a population of patients with gastric and colonic cancers showed improved survival with this treatment. A randomized trial of combined chemoimmunotherapy versus chemotherapy alone was begun on November 1, 1974, for all cancers of the stomach and pancreas and all colorectal cancers beyond stage C by Dukes' classification. The initial results with patients entered by December 31, 1975, and followed until March 1, 1976, are reported.

Adjuvant immunostimulation in malignant melanoma with oral Bacille Calmette-Guérin.

Results of the administration of oral bacille Calmette-Guérin (BCG) as an adjunct to standard treatment in 62 patients with malignant melanoma indicate that this drug is of value in preventing distant spread of the disease when it is limited to one region and in its early stages. BCG increases survival in patients with visceral metastases. In those in whom these metastases are surgically resectable, it inhibits the development of further metastases. Oral BCG treatment does not affect the course of the disease in patients with massive hepatic or intracranial metastases.