459 research outputs found
Clinical and translational imaging keeps growing: thanks to its board members, authors and readership
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The ketogenic diet increases in vivo glutathione levels in patients with epilepsy
The Ketogenic Diet (KD) is a high-fat, low-carbohydrate diet that has been utilized as the first line treatment for contrasting intractable epilepsy. It is responsible for the presence of ketone bodies in blood, whose neuroprotective effect has been widely shown in recent years but remains unclear. Since glutathione (GSH) is implicated in oxidation-reduction reactions, our aim was to monitor the effects of KD on GSH brain levels by means of magnetic resonance spectroscopy (MRS). MRS was acquired from 16 KD patients and seven age-matched Healthy Controls (HC). We estimated metabolite concentrations with linear combination model (LCModel), assessing differences between KD and HC with t-test. Pearson was used to investigate GHS correlations with blood serum 3-B-Hydroxybutyrate (3HB) concentrations and with number of weekly epileptic seizures. The results have shown higher levels of brain GSH for KD patients (2.5 ± 0.5 mM) compared to HC (2.0 ± 0.5 mM). Both blood serum 3HB and number of seizures did not correlate with GSH concentration. The present study showed a significant increase in GSH in the brain of epileptic children treated with KD, reproducing for the first time in humans what was previously observed in animal studies. Our results may suggest a pivotal role of GSH in the antioxidant neuroprotective effect of KD in the human brain
Optical imaging probes in oncology
Cancer is a complex disease, characterized by alteration of different physiological molecular processes and cellular features. Keeping this in mind, the possibility of early identification and detection of specific tumor biomarkers by non-invasive approaches could improve early diagnosis and patient management.Different molecular imaging procedures provide powerful tools for detection and non-invasive characterization of oncological lesions. Clinical studies are mainly based on the use of computed tomography, nuclear-based imaging techniques and magnetic resonance imaging. Preclinical imaging in small animal models entails the use of dedicated instruments, and beyond the already cited imaging techniques, it includes also optical imaging studies. Optical imaging strategies are based on the use of luminescent or fluorescent reporter genes or injectable fluorescent or luminescent probes that provide the possibility to study tumor features even by means of fluorescence and luminescence imaging. Currently, most of these probes are used only in animal models, but the possibility of applying some of them also in the clinics is under evaluation.The importance of tumor imaging, the ease of use of optical imaging instruments, the commercial availability of a wide range of probes as well as the continuous description of newly developed probes, demonstrate the significance of these applications. The aim of this review is providing a complete description of the possible optical imaging procedures available for the non-invasive assessment of tumor features in oncological murine models. In particular, the characteristics of both commercially available and newly developed probes will be outlined and discussed
Hypoxia-inducible factor-1α activity as a switch for glioblastoma responsiveness to temozolomide
Rationale: The activity of the transcription factor, hypoxia-inducible factor (HIF)-1\u3b1, is a common driver of a number of the pathways involved in the aggressiveness of glioblastomas (GBMs), and it has been suggested that the reduction in this activity observed, soon after the administration of temozolomide (TMZ), can be a biomarker of an early response in GBM models. As HIF-1\u3b1 is a tightly regulated protein, studying the processes involved in its downregulation could shed new light on the mechanisms underlying GBM sensitivity or resistance to TMZ. Methods: The effect of HIF-1\u3b1 silencing on cell responsiveness to TMZ was assessed in four genetically different human GBM cell lines by evaluating cell viability and apoptosis-related gene balance. LAMP-2A silencing was used to evaluate the contribution of chaperone-mediated autophagy (CMA) to the modulation of HIF-1\u3b1 activity in TMZ-sensitive and TMZ-resistant cells. Results: The results showed that HIF-1\u3b1 but not HIF-2\u3b1 activity is associated with GBM responsiveness to TMZ: its downregulation improves the response of TMZ-resistant cells, while blocking CMA-mediated HIF-1\u3b1 degradation induces resistance to TMZ in TMZ-sensitive cells. These findings are in line with the modulation of crucial apoptosis-related genes. Conclusion: Our results demonstrate the central role played by HIF-1\u3b1 activity in determining the sensitivity or resistance of GBMs to TMZ, and we suggest that CMA is the cellular mechanism responsible for modulating this activity after TMZ treatment
Diagnosis and treatment of pulmonary embolism: a multidisciplinary approach
The diagnosis of pulmonary embolism (PE) is frequently considered in patients presenting to the emergency department or when hospitalized. Although early treatment is highly effective, PE is underdiagnosed and, therefore, the disease remains a major health problem. Since symptoms and signs are non specific and the consequences of anticoagulant treatment are considerable, objective tests to either establish or refute the diagnosis have become a standard of care. Diagnostic strategy should be based on clinical evaluation of the probability of PE. The accuracy of diagnostic tests for PE are high when the results are concordant with the clinical assessment. Additional testing is necessary when the test results are inconsistent with clinical probability. The present review article represents the consensus-based recommendations of the Interdisciplinary Association for Research in Lung Disease (AIMAR) multidisciplinary Task Force for diagnosis and treatment of PE. The aim of this review is to provide clinicians a practical diagnostic and therapeutic management approach using evidence from the literature. © 2013 Lavorini et al
Validation of an Engineered Cell Model for In Vitro and In Vivo HIF-1 alpha Evaluation by Different Imaging Modalities
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High-resolution technetium-99m-HMPAO SPECT in patients with probable Alzheimer's disease : comparison with fluorine-18-FDG PET
SPECT studies of regional cerebral perfusion with a high-resolution system were compared to PET studies of regional cerebral glucose utilization (rCMRglc) in 21 patients with probable Alzheimer's disease (AD). Ten normal subjects were also evaluated with SPECT and 10 with PET.
METHODS:
rCMRglc (for PET) and counts (for SPECT) in the associative cortices were normalized to the average rCMRglc, and counts in the calcarine cortex and basal ganglia were considered as a "reference area" to obtain a ratio. The ratio differences between patients and controls were tested with ANOVA performed separately for PET and SPECT.
RESULTS:
The difference between probable AD patients and controls was significant for both PET (p < 0.00001) and SPECT (p < 0.005); this difference was significant for the frontal, temporal and parietal cortices (p < 0.0001) for PET, and for the temporal (p < 0.005) and parietal (p < 0.001) cortices for SPECT. Temporo-parietal defects were detected in all subjects with PET and in 90% with SPECT.
CONCLUSION:
PET and SPECT are able to detect characteristic temporo-parietal abnormalities in probable AD. However, the presence of abnormalities in other associative areas is better evaluated with PET
Secondary cytomegalovirus infections: How much do we still not know? Comparison of children with symptomatic congenital cytomegalovirus born to mothers with primary and secondary infection
congenital cytomegalovirus (cCMV) infection can follow primary and secondary maternal infection. growing evidence indicate that secondary maternal infections contribute to a much greater proportion of symptomatic cCMV than was previously thought. We performed a monocentric retrospective study of babies with cCMV evaluated from august 2004 to february 2021; we compared data of symptomatic children born to mothers with primary or secondary infection, both at birth and during follow up. among the 145 babies with available data about maternal infection, 53 were classified as having symptomatic cCMV and were included in the study: 40 babies were born to mothers with primary infection and 13 babies were born to mothers with secondary infection. Analyzing data at birth, we found no statistical differences in the rate of clinical findings in the two groups, except for unilateral sensorineural hearing loss (SNHL) which was significantly more frequent in patients born to mother with secondary infection than in those born to mother with primary infection (46.2 vs. 17.5%, P = 0.037). during follow up, we found a higher rate of many sequelae (tetraparesis, epilepsy, motor and speech delay, and unilateral SNHL) in the group of children born to mothers with secondary infection, with a statistical difference for tetraparesis and unilateral SNHL. otherwise, only children born to mothers with primary infection presented bilateral SNHL both at birth and follow up. Our data suggest that the risk of symptomatic cCMV and long-term sequelae is similar in children born to mother with primary and secondary CMV infection; it is important to pay appropriate attention to seropositive mothers in order to prevent reinfection and to detect and possibly treat infected babies
Differentiation of clinically non-functioning pituitary adenomas from meningiomas and craniopharyngiomas by positron emission tomography with [18F]fluoro-ethyl-spiperone
The differential diagnosis among various types of non-functioning sellar and parasellar rumours is sometimes difficult using currently available methods of morphological imaging. The aim of this study was to define whether assessment of the uptake of [F-18]fluoro-ethyl-spiperone (FESP) with positron emission tomography (PET) could be helpful for the differential diagnosis of pituitary adenomas and other parasellar lesions, and for establishing the appropriate therapeutic approach, The population examined comprised 16 patients with the diagnosis of primary tumour of the sellar/parasellar region who were waiting to undergo surgical treatment. The results demonstrated that PET with [F-18]FESP is a very specific method for differentiating adenomas from craniopharyngiomas and meningiomas. The visual interpretation of images allows such differentiation at approximately 70 min after tracer injection. Semiquantitative analysis of the dynamic PET data confirmed the results of visual interpretation, demonstrating that the uptake of [F-18]FESP was consistently (i.e. throughout the series) at least two-to threefold higher in non-functioning adenomas than in other parasellar rumours as early as 70 min after tracer injection, and that it increased still further thereafter. It is concluded that PET with [F-18]FESP might be of clinical value in those cases in which the differential diagnosis among various histological types of sellar tumour is uncertain with conventional methods
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