Floating-Harbor Syndrome: Presentation of the First Romanian Patient with a SRCAP Mutation and Review of the Literature.

Floating-Harbor syndrome (FHS) is a rare autosomal dominant syndrome characterized by short stature with delayed bone age, retarded speech development, intellectual disability and dysmorphic facial features. Recently, dominant mutations almost exclusively clustered in the final exon of the Snf2-related CREBBP activator protein (SRCAP) gene were identified to cause FHS. Here, we report a boy with short stature, speech delay, mild intellectual disability, dysmorphic features, and with genetically confirmed FHS. To the best of our knowledge, this is the first molecularly confirmed case with this syndrome reported in Romania. An intensive program of cognitive and speech stimulation, as well as yearly neurological, psychological, ophthalmological, otorhinolaryngological, pediatric and endocrinological monitoring for our patient were designed. We propose a checklist of clinical features suggestive of FHS, based on the main clinical features, in order to facilitate the diagnosis and clinical management of this rare condition.

Temporal profiling of depression vulnerability in a preclinical model of sustained depression.

Major Depression is a prevalent mental disorder that is characterized by negative mood and reduced motivation, and frequently results in social withdrawal and memory-related deficits. Repeated stressors, such as adverse life events, increase the risk for development of the disorder. Consequently, individual variability in stress response greatly weighs on depression-vulnerability and -resilience. Here, we employed the social defeat-induced persistent stress (SDPS) paradigm to identify depression-prone individuals and to examine the temporal development of depression in the months following exposure to brief defeat stress. Male Wistar rats were socially defeated (5 defeat episodes) and single-housed for a prolonged period of time (~24 weeks). We assessed the emergence of a sustained depressive-like state by repeatedly evaluating social motivation (social approach avoidance) and spatial memory (object place recognition) in SDPS rats during the isolation period. Individual variability in the effects of SDPS yielded two extreme subpopulations: an SDPS-prone group that showed gradual affective and cognitive deterioration in terms of social approach and memory retention, and a SDPS-resilient group that did not develop this phenotype. Notably, in SDPS-prone individuals, the affective deficits preceded later cognitive impairments, providing a novel temporal profile of the development of pathology in this preclinical model of sustained depression.

Apoptosis, paraptosis, necrosis, and cell regeneration in posttraumatic cerebral arteries.

This study is to understand the nature and functional significance of the activated cell death programs and rehabilitation signs during late vascular changes after brain injury. We used light and transmission electron microscopy to describe changes of cells within the vascular endothelium and tunica media of the cortical arteries four weeks after craniocerebral traumatism. Within tunica media of the posttraumatic damaged artery, apoptotic and paraptotic phenotypes were identified as well as some early ultrastructural signs of smooth muscle cells regeneration, these cell highlighting a remarkable degree of plasticity. Surprisingly, some endothelial cells showed an extensive rough endoplasmic reticulum development, whereas other endothelial cells showed typical necrosis. In conclusion, two groups of suicidal cells apoptotic and paraptotic cells were encountered in the same lesional vascular wall after neurotrauma, showing also signs of cell regeneration. The pathophysiologic significance of the coexisting double cell death programs and cell regeneration seems to be in relation with late cell survival, after arterial damage when some cells disappear and other cells try to survive undergoing reversible injury.

Regenerative medicine: Antagonic-Stress therapy in distress and aging. I. Preclinical synthesis--2003.

Repetitive and cumulative distress (acute and/or chronic, psychic and/or biologic) and aging processes (impairment phenomena, agglomerated, and accumulated with the passing of life and senescence periods), as well as distress <==> aging reciprocal amplification-accelerating-aggravation relationships require strong and rational (etiopathogenic) therapeutic interventions. Therefore, the drug, Antagonic-Stress (AS)--a new integrative therapy, with specific synergistic formula, being patented worldwide--becomes an important solution in distress, senescence, and their related pathologies. In acute (contention) stress, AS treatment significantly decreased rat mortality, number and surface of stomach ulcerations, nonesterified fatty acids (NEFAs), and increased superoxide dismutase (SOD) from blood. In chronic psychic stress, live nerve cells selectively isolated from rat cerebral cortex were highly protected by the administration of AS. In addition, antistress and antiaging homeostatic actions of AS were demonstrated in accelerated senescence (aging + distress) at multiple brain levels: on functional anabolism [increase in total ribonucleic acids (RNA), total proteins (TP), and water-soluble proteins (WSP)]; on functional catabolism [decrease in water-insoluble proteins (WIP)]; on structural anabolism (increased regeneration of free ribosomes, rough endoplasmic reticulum, mitochondria, and Nissl bodies); on structural catabolism (lipofuscinolysis and ceroidolysis, neurono-glial transfer of lipopigment continuously processed and dissoluted, and finally capillary elimination). Preclinical research with AS demonstrated important regenerative processes in the key organs (liver, heart, and brain), which mostly suffer due to both distress and senescence.

Prolongevity medicine: Antagonic-Stress drug in distress, geriatrics, and related diseases. II. Clinical review--2003.

Distress and senescence, their reciprocal aggravating-quickening connections, and their related pathologies have a large worldwide impact on healthcare systems in this new millennium. For this reason, Antagonic-Stress (AS)--an advanced integrative therapy, with specific synergistic composition, and patented internationally--represents a significant strategy in health, aging, and longevity. Clinical research with AS proves the drug's efficacy in the management of distress (neurotic, stress-related, and affective disorders; behavioral syndromes associated with physiological disturbances and physical factors; mental and behavioral disorders due to psychoactive substance uses) and psychogeriatrics [organic, including symptomatic, mental disorders (OMD)]. Specific multiaxial psychopathological instruments and psychometric tests in multiple assessments used for gerontopsychiatry demonstrated strong improvements after AS administration in early-moderate stages of Alzheimer or vascular dementia, as well as in other OMD. In addition, comparative clinical studies evinced the superiority of AS (synergistic multitherapy) versus monotherapy [meclofenoxate (MF), piracetam (PA), pyritinol (PT), and nicergoline (NE), respectively]. These comparative clinical trials agreed closely with comparative preclinical research and confirmed AS synergistic homeostatic, adaptogenic, antioxidative, cerebrovascular, neurometabolic, and nootropic actions. Also, the AS protective actions against oxidative stress recommend this orthomolecular therapy in stress, aging, and free radical pathology.

An antistress and antiaging neurometabolic therapy. Accelerated lipofuscinolysis and stimulated anabolic regeneration by the antagonic-stress synergistic formula.

In both stress and aging, an etiopathogenic analysis demonstrates in the brain some common mechanisms and reciprocal accelerating relationships: hypoanabolism (decrease of RNA and protein synthesis), coupled with hypercatabolism (increase of oxidative stress-lipid peroxidation, with waste product accumulation: lipofuscinage pigment and water-insoluble proteins). For therapeutical intervention in these antihomeostatic processes, we successively (1972-1992) developed a neurometabolic antioxidative therapy--finally represented by a specific antistress and antiaging synergistic formula, Antagonic-Stress. Its homeostatic actions have been demonstrated in the stressed aging brains by reestablishing the anabolism/catabolism balance: anabolic regeneration by increasing total RNA, total proteins and water-soluble proteins, coupled with catabolic regulation by accelerated lipofuscinolysis and age pigment elimination (neuronal-->glial-->capillary route) and decreasing of water-insoluble proteins. Specific, synergistic, and superior actions of Antagonic-Stress multiple formula vs. antistress and antiaging monotherapy have been demonstrated by preclinical and clinical studies, confirming our results.

Brain lipofuscinolysis and ceroidolysis--to be or not to be.

Lipofuscin pigment (LP) accumulations and ceroid pigment (CP) storages were demonstrated by multiple consensus studies. On the contrary, fewer researches, sometimes with opposite conclusions were made on brain LP and CP decrease, dissolution and elimination. Neuroactive agents (such as Meclofenoxate, Orotic acid, Antagonic-Stress, Piracetam, L-Deprenyl, Geriforte) generate LP and CP decrease and dissolution by cytoplasm rehydration, optimization of the brain cellular recycling system activities, by neuronal, glial and capillary LP lysis and CP lysis, by neurono-glio-endothelial transfer of highly processed LP and CP, with final capillary elimination. Therefore, these nootropic drugs may become therapeutical solutions in brain aging deceleration, in CP inductive circumstances and in age-associated diseases.

Antagonic-stress. A new treatment in gerontopsychiatry and for a healthy productive life.

A complex antiaging formula--Antagonic-Stress--was investigated vs. placebo (PL), meclofenoxate (MF)--neurometabolic nootropic and vs. nicergoline (NE)--cerebral vasodilator by comparative multiple trials (double-blind, randomized, and parallel) in gerontopsychiatry (DSM-III-R, 1987 and ICD-10, 1992 criteria). AS vs. PL studies in organic mental disorders--amnestic, depressive, anxiety, associated with axis III physical disorders or conditions, and in multiinfarct dementia were followed by AS vs. MF or NE investigations in senile dementia of Alzheimer's type. A total of 343 old people, distributed in 4 PL groups, 1 MF group, 1 NE group, and 5 AS groups were studied. Multiple investigations, before and after three-month treatments were made: psychometric evaluation by Sandoz Clinical Assessment-Geriatric, Self-Assessment Scale-Geriatric and their 5 subscales; psychopathological rating by Hamilton Depression and Anxiety Scales; as well as psychometric testing by digit symbol of WAIS, Wechsler Memory Scale and Wechsler Adult Intelligence Scale (WAIS). Except PL, prolonged and large dose treatments with these cerebral activators (MF, NE and especially AS) reduced the psychogeriatric-psychopathological scores and the deterioration index, and improved cognitive performance. The therapeutical effectiveness of AS multiple formula in gerontopsychiatry and its superiority vs. monotherapy (MF or NE) are discussed in connection with its complex neurometabolic and synergetic composition, multiple antioxidative combinations, free radical scavengers, lipofuscinolytic agents, the antiischemic action of antioxidants, multivitamin and multimineral supplementation, and with the better efficacy of multitherapy vs. monotherapy in geriatrics.

Antagonic-stress: A therapeutic composition for deceleration of aging. I. Brain lipofuscinolytic activity demonstrated by light and fluorescence microscopy.

The dynamics, the histochemical and morphological characteristics of brain lipopigment (LP: lipofuscin and ceroid) were studied after 8 weeks of daily administration of Antagonic-Stress (AS), a new combination of various compounds used in cerebroprotection and the treatment of cerebral senescence. LP features of treated old (TO), control old (CO) and control adult (CA) groups of 60 Wistar male rats were compared by morphometry, light and fluoresence microscopy. AS administration produced a general, intense and selective decrease of LP from TO group: 48. 1 and 39.6% in various cerebral cortex areas, 47.5% in hippocampus, 47.3-37.2% in brain stem reticular formation, 38.8% in hypothalamus and 34.1% in Purkinje cell layer in comparison with CO group. In addition, histochemical and morphological characteristics of LP in TO group were modified and were close to those of CA group, represented by an active transformation of their chemical constituents and intracellular architecture. The decrease and dissolution of LP may be explained by the inhibition of LP genesis, associated with the acceleration of LP lysis (lipofuscinolysis and ceroidolysis), transfer and elimination. Our findings indicate that LP dynamics, histochemical and morphological characteristics may be manipulated by nootropic and anti-aging drugs, which actively interfere with LP genesis and lysis.

Antagonic-stress: A therapeutic composition for deceleration of aging. II. Brain lipofuscinolytic activity demonstrated by electron microscopy.

Electron microscopic morphology and distribution of brain lipofuscin and ceroid (LP) were studied after 8 weeks of daily treatment with Antagonic-Stress (AS), a new combination of various components with cerebroprotective and anti-aging properties. LP characteristics were investigated in selected brain areas of control adult (CA), control old (CO) and treated old (TO) groups of 30 male Wistar rats. Cellular and regional distributions of LP in the TO group were very different from those of the CO group and resembled that of the CA group. In addition, electron microscopic signs of dissolution of LP were constantly observed in the TO group. Neurons and glia cells of TO group displayed an intense replacement of damaged organelles, especially of mitochondria, with normal organelles, many of them in hyperfunctional stages. Neuronal, glial and capillary LP lysis occurred simultaneously with neuro-glial LP transfer and capillary LP elimination. Numerous microglia cells overloaded with processed LP were identified in the vicinity of the capillary areas. AS treatment of 8 weeks induces lysis of LP which may be useful for therapeutic purposes in various brain pathologies and in deceleration of brain aging in healthy elderly.