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Medical Lake, United States

Novegno F.,Catholic University Medical School
Advances and technical standards in neurosurgery | Year: 2012

Tuberous Sclerosis Complex (TSC) is an autosomal dominant multisystem disorder, characterized by the presence of hamartomatous lesions involving different organ systems, including the brain. Epilepsy is the most common presenting symptom, representing a major source of morbidity and mortality. Despite multiple antiepileptic drug combinations, in about two thirds of cases the patients present high-frequency drug-resistant epilepsy, and nonpharmacologic options may be considered. The aim of this work was to point out the current knowledge on epileptogenesis in TSC, the available medical therapies and diagnostic tools, and possible surgical strategies, with the intent to better understand the actual difficulties in controlling seizures and the results reported in the literature. There is also a section dedicated to the common association with cognitive impairment and the role of epilepsy control on its outcome. Source

Campia U.,MedStar Research Institute | Tesauro M.,University of Rome Tor Vergata | Di Daniele N.,University of Rome Tor Vergata | Cardillo C.,Catholic University Medical School
Life Sciences | Year: 2014

Obesity, the metabolic syndrome (MetS), and type 2 diabetes (T2DM) are associated with heightened cardiovascular risk. Given the vasoconstrictor and proatherogenic properties of endothelin (ET)-1, increased ET-1 activity has been postulated to participate in the derangement of adiposity-related vascular homeostasis. This concept is supported by human studies using receptor antagonists to show that the activity of endogenous ET-1 is indeed enhanced in overweight and obesity, the MetS, and T2DM. Also, increased ET-1 contributes to endothelial dysfunction related to obesity, the MetS, and T2DM, whereas decreasing ET-1 vasoconstrictor tone in these patients corrects the defective endothelium-dependent vasodilation. In addition, in patients with central adiposity and the MetS, enhanced intravascular ET-1 activity coexists with decreased nitric oxide (NO)-dependent vasodilator capacity, suggesting a prevalence of vasoconstrictor mediators in vessels of obese individuals. One mechanism evoked to explain the development of vascular abnormalities in obesity deals with the derangement of the physiological vascular effects of insulin in insulin-resistant states. Thus, in conditions of adiposity, defective insulin-mediated vasodilation leads to impaired ability of the hormone to enhance its delivery and that of substrates to peripheral tissues. An important role of ET-1 in this abnormality is supported by studies showing that upregulation of the ET-1 system impairs NO-mediated vasodilation in insulin-resistant patients, whereas NO bioactivity is restored following ET-1 antagonism. In conclusion, considerable evidence supports a mechanistic role of ET-1 in the pathophysiology of adiposity-related vascular dysfunction. Targeting the ET-1 system, therefore, might have the potential for effective cardiovascular prevention in obesity, the MetS, and T2DM. © 2014 The Authors. Source

Dilation of the renal pelvis is a problem Urologists have often to deal with. One of the key aspects is to clear if the dilation is the consequence of an obstruction to the outflow or a simple anatomic variant. Aim of this study was to compare two diuretic renographic procedures, F-15 vs the new procedure F+10SP (Seated Position) in a group of hydronephrotic patients, in order to increase the accuracy in the differential diagnosis between non-obstructive and obstructive dilation. 34 Patients (14 male, 20 female, 18-71 yrs range), 27 pts having an unilateral hydronephrosis and 7 pts a bilateral hydronephrosis diagnosed by ultrasound, were enclosed in the study. They were subjected to two 99mTc-MAG3 diuretic renography with furosemide consecutively, with different modalities: 1) 40 mg of furosemide were administered IV to patient in supine position 15 minutes before tracer injection (Test F-15, by English); 2) the new procedure: 20 mg of furosemide were administered IV to patient in Seated Position (SP), 10 minutes after tracer injection during dynamic acquisition (Test F+10 SP). The average interval between the two tests was 7 days. Two different physicians analyzed all the tests. The results were classified as: non-obstruction (only F+10SP can distinguish between normal and dilated without obstruction), obstruction, equivocal and not applicable. Among the 68 renal units (RU) included in the analysis, the F+10SP test showed normal findings in 21 RU (30,8%), dilation without obstruction in 21 RU (30,8%), obstruction in 25 RU (36.8%) and equivocal result in 1 RU. The F-15 renography showed non-obstructive results in 35 RU (51.5%), obstruction in 20 RU (29.4%) and equivocal findings in 11 RU (16.1%); the test was not applicable in 2 RU (2.9%) due to insufficient renal function. Side effects reported for the F-15 renogram were hypotension in 1 patient, renal colic in 3 patients, bladder filling in 13 patients, disruption because of voiding in 4 patients. No complications were observed during or after the F+10SP renography. The 20 RU diagnosed with obstruction at the F-15 test were considered obstructed also at the F+10SP test. The "equivocal" test rate lowered from 16% for the F-15 test to less than 1.5% for the new F+10 SP test. The F+10SP procedure is easy, well tolerated, time saving and seems to be a more reliable tool in assessment of obstructive uropathy in adults. Source

Fusco S.,Catholic University Medical School | Pani G.,Catholic University Medical School
Cellular and Molecular Life Sciences | Year: 2013

Calorie restriction extends longevity and delays ageing in model organisms and mammals, opposing the onset and progression of an array of age-related diseases. These beneficial effects also extend to the maintenance of brain cognitive functions at later age and to the prevention, at least in rodents, of brain senescence and associated neurodegenerative disorders. In recent years, the molecular mechanisms underlying brain response to calorie restriction have begun to be elucidated, revealing the unanticipated role of a number of key nutrient sensors and nutrient-triggered signaling cascades in the translation of metabolic cues into cellular and molecular events that ultimately lead to increased cell resistance to stress, enhanced synaptic plasticity, and improved cognitive performance. Of note, the brain's role in CR also includes the activation of nutrient-sensitive hypothalamic circuitries and the implementation of neuroendocrine responses that impact the entire organism. The present review addresses emerging molecular themes in brain response to dietary restriction, and the implications of this knowledge for the understanding and the prevention of brain disorders associated with ageing and metabolic disease. © 2012 Springer Basel. Source

Sacco E.,Catholic University Medical School | Bientinesi R.,Catholic University Medical School
International Urogynecology Journal and Pelvic Floor Dysfunction | Year: 2015

Introduction and hypothesis: The impressive prevalence of overactive bladder (OAB) and the relevant limitations of current treatments urge the need for novel therapeutic approaches. Methods: A systematic literature and web search was performed to identify investigational drugs that entered the early and late phases of clinical development for women with OAB symptoms. Results: Approved pharmacological therapies for OAB (antimuscarinics, beta-3 agonists, and botulinum toxin) are evolving with the development of alternative administration methods, combination strategies, and novel compounds, expected to improve effectiveness, bladder selectivity, and dose flexibility. A wealth of investigational compounds, developed with both public and companies’ indoor nonclinical disease-oriented studies, entered the early and late stages of clinical development in the last decade. Most non-anticholinergic compounds in ongoing clinical trials target central and peripheral neurotransmitter receptors involved in neurological modulation of micturition, nonadrenergic-noncholinergic mechanisms, cyclic nucleotide metabolism, different subtypes of ion channels or peripheral receptors of prostaglandins, vanilloids, vitamin D3, and opioids. Fascinating advances are ongoing also in the field of genetic therapy. Conclusions: New pharmaceutical formulations and drug combinations are expected to be available in the next decade in order to overcome the limitations of current drugs for OAB. Although proof-of-concept, patient-oriented studies yielded disappointing results for several tentative drugs, a lot of clinical research is ongoing that is expected to provide clinicians with novel therapeutic agents in the near future. © 2014, The International Urogynecological Association. Source

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