Acetaldehyde effects in the brain

The effects of alcohol have been widely studied during the past century as alcohol abuse is a major health problem in Western society. In the last years, a growing body of evidence indicates that acetaldehyde, the first oxidation product of ethanol, is one of the mediators of peripheral and central effects of ethanol. Indeed, acetaldehyde has been recently taken into account as the mediator of the rewarding properties of alcohol. The role of acetaldehyde in ethanol-related properties has been proved by enzymatic manipulation studies in which the inactivation of acetaldehyde potentially synthesized in the brain produces the same results as blocking the formation of acetaldehyde by inhibiting…

Role of acetaldehyde in alcohol addiction: current evidence and future perspectives

The effects of alcohol have been widely studied during the past century, corroborating the idea that this tiny chemical compound acts throughout most of our neurotransmitter systems since it is capable of inducing addictive behaviour. Two of the most serious problems of alcohol addiction are craving and relapse; several studies have demonstrated that relapse is related to the anxious state which occurs during withdrawal, and it has been proved that this behavioural modifications results from an alteration of the dopaminergic and serotonergic systems. An important role in the neurobiology of alcohol addiction is played by acetaldehyde (ACD), ethanol first metabolite. Our recent studies indee…

Pirrolomicine che inibiscono la Sortasi A nelle infezioni sostenute da batteri Gram-positivi

La Sortasi A è un enzima di membrana responsabile dell’ancoraggio delle proteine di superficie sulla parete cellulare dei batteri Gram-positivi. Essa è considerata un interessante obiettivo per lo sviluppo di nuovi farmaci anti-infettivi che mirino ad interferire con importanti meccanismi di virulenza Gram-positivi. In un precedente lavoro abbiamo indagato sull’attività antistafilococcica e antibiofilm di alcune Pirrolomicine naturali e sintetiche, composti pirrolici polialogenati attivi su patogeni Gram-positivi, alle concentrazioni di 1.5 e 0.045 µg/mL. I risultati biologici hanno mostrato percentuali di inibizione di biofilm comprese tra 50-80% [1]. Allo scopo di indagare sul loro meccan…

Hearing loss in neonatal intensive care units (NICUS): Follow-up surveillance

Infants admitted to the neonatal intensive care unit (NICU), who represent the 4-8% of all births, present problems such as prematurity, low Apgar scores, infections, hyperbilirubinemia and hearing impairment. In particular significant hearing loss is the most common disorder at birth, occurring in 1 to 2 newborns per 1000 in the general population and 24% to 46% of newborns who are admitted to a NICU. This leads more difficulty to develope verbal skills (learning vocabulary, grammar, word order and idiomatic expressions), language, learning and speech. Hearing impairment influences also cognitive and affective development of infants making consequences in their interpersonal relationships.…

Impact of a single, intense prenatal stress on ethanol drinking behaviour and cognition in adult male rats

Early exposure to stressful stimuli is crucial for developing varied behavioural patterns in adulthood such as anxiety, cognitive dysfunction and abuse disorders. The alteration of the hypothalamic–pituitary–adrenal (HPA) axis represents the neurobiological substrate responsible of the behavioural consequences of prenatal stress (PS). Indeed, prenatal manipulation of the HPA axis impacts on cognitive performance of the adult offspring, but also on vulnerability to alcohol consumption. Prenatal acute, moderate restraint stress has proved to facilitate HPA axis development of the offspring, since maternal corticosterone secretion leads to the reduction of anxiogenic behaviour and an improveme…

A facile synthesis of 1-ethyl-3-methyl-11-phenyl-1,4-dihydro-5H-pyrazolo[3,4-c][1,5]benzodiazocin-5-ones. A new ring system

The new ring system pyrazolo[3,4-c][1,5]benzodiazocine was obtained through cyclization of the key intermediate of type 6a-d and 9, in refluxing toluene in presence of a catalytic amount of p-toluensulfonic acid, from moderate to high yields

Association between sleep-disordered breathing and hearing disorders: Clinical observation in Sicilian patients

Introduction: To examine the putative association between Sleep-Disordered breathing and hearing disorders Material and methods: 120 Sicilian subjects ranging from 14 to 85 years of age who were divided in 46 cases suffering from tinnitus (G1 group) and 74 controls (G2 group) were evaluated through STOP BANG screening questionnaire and Four-Variable Screening Tool; after Data collecting each subject underwent Audiological assessment by multi-frequency audiometry (PTA) and Transient-evoked otoacoustic emissions (TEOAE-diagnostic) for each ear. Results: Cases showed: PTA significantly severe than the control group (58.70% vs. 16.89% hearing loss; P<0.001), such as a lower signal-to-noise r…

Emerging pharmacological treatments of tinnitus

Tinnitus is not a disease, but rather a symptom or condition characterized by a conscious perception of an unreal sound in the absence of external auditory stimulus. This ontological condition can modify everyday life in different ways: causing distress and annoyance, sleep disruption, anxiety and depression. The World Health Organization (WHO) describes tinnitus as a symptom of hearing disorder characterized by the sensation of buzzing, ringing, clicking, pulsations, grinding, hissing, roaring or other noises in the ear. Even if different treatments exist for “tinnitus-related abnormalities” such as cognitive behavioural therapy and/or sound therapy, no effective pharmacological approa…

Pharmacological treatment of sensorineural hearing loss

Sudden sensorineural hearing loss is a common and alarming symptom of about 360 million people that suffer from hearing impairment worldwide. The sudden sensorineural hearing loss usually arises unilaterally and it is habitually described as greater than 30dB hearing reduction, attributable to lesions of the cochlea, cranial nerve VIII, brainstem and temporal lobe. There are many factor that promote the onset of this lesions such us infections, circulatory diseases, inner ear neoplasia and neurological disorders. This pathology is characterized by primary symptoms such as the impairment of the comprehension of spoken language and the struggling to listen to music. Subsequently, secondary sy…

Role of cannabinoids in the treatment of tinnitus

Tinnitus is a frequent symptom in audiological clinical practice characterized by an abnormal noise perceived in one or both ears or in the head, in which a patient has a conscious hearing percept in absence of external sound. Tinnitus might be caused by a homeostatic response of central dorsal cochlear nucleus auditory neurons that makes them hyperactive in compensation to auditory input loss. One hypothesis suggests that tinnitus is a sensory form of epilepsy that involves the cochlear nucleus and the inferior colliculus, which display impairment in the electrical activity in the auditory system. This alteration determines a synaptic plasticity in the dorsal cochlear nucleus that becomes …

Synthesized benzamido derivatives exert antiproliferative effects by DNA damage and ROS generation.

In this study we explored the effect and the biological action of synthesized benzamido derivatives bearing the (1S,2S)-2-phenyl-cyclopropane-1-carboxamido, 1,1'-biphen-2-carboxamido and 1,1'-biphen-4-carboxamido moieties on K562, a human leukemia cell line. Among the synthesized compounds a particular antiproliferative action was observed with the benzamido derivative bearing the 2-1,1'-biphenyl moiety with the substitution at the 5 position of the benzamido moiety with iodine. This compound showed cytotoxic effects in K562 leukemic cells at nanomolar concentrations and was, therefore, chosen as compound to explore its mode of action. Our analyses provided evidence that this benzamido deri…

Synthesis and antirpoliferative activity of isoxazolo[3,4-d]pyridazin-7(6H)-one derivatives

3,4-diphenylisoxazolo[3,4-d]pyridazin-7(6H)-one analogs were synthesized and tested for the antiproliferative activity. Study on the cell cycle alteration and on some cellular target (ATM, procaspase-2 proteins and H2AX histone) demonstrate the increase of the cell population in S phase and to induce cellular death by apoptosis by DNA damage with double strand breaks.

Brief maternal separation procedures occurring early in life affect learning and memory in adult Wistar rats: sex-related differences in cognitive behaviour

Adverse life events during the neonatal period result in long-term effects on physiology and behavior. Early postnatal experiences, such as a modification of the mother–infant interaction, may influence the development of neural systems that underlie the expression of neuroendocrine and behavioural responses to environmental challenges. The present study was carried out to investigate the consequences of a brief, maternal separation on declarative and spatial memory, focusing on sex related alteration due to the discrete effects that hormones may play on the brain circuits. Our results indicate that a brief, daily maternal separation results in sexually-dimorphic cognitive alterations that …

Sintesi di un isostero del 3,5-dimetil-6-fenil-8-(trifluorometil)-5,6-diidropirazolo[3,4-f][1,2,3,5]tetrazepin-4(3H)-one (CF3-TZP) con potenziale attività biologica

In un precedente lavoro abbiamo mostrato i risultati relativi alla sintesi ed all’attività biologica del CF3-TZP 1[1] (Figura 1). Le attività antiproliferativa e apoptotica del composto 1 sono state testate su differenti linee cellulari, HL60 sensibili, HL60-R (MDR), K562 e K562-R (resistenti al Gleevec®), mostrando un profilo di attività biologica similare sulle cellule sensibili e resistenti nel range di 21-40 µM per l’IC50 e 36-62 µM per l’AC50. L’analisi citofluorimetrica sulle K562 sensibili ha indicato che il composto 1 determina un arresto dose-dipendente del ciclo cellulare in fase G0-G1 nelle prime 24 h di trattamento, mentre nelle successive 24 h si è notato una riduzione del picc…

Pharmacological therapy of newborn babies admitted to the neonatal intensive care unit

Newborn babies who need intensive medical care are often sheltered into a special area of the hospital called Neonatal Intensive Care Unit (NICU). In this structure, babies are regularly subject to conditions that would be considered harmful by older children and adults. In the last years, many clinical researches have paid particular attention to effectiveness of various pharmacological therapies, regularly used in neonatal intensive care that have sharply reduced mortality of newborn and preterm infants. Although there are many classes of drugs used for the treatment of different diseases (sepsis, pain, seizures, pulmonary hypertension and infection), the fledgling population is more diff…

Progettazione e sintesi di nuovi derivati 4-chinazolinonici potenziali inibitori della diidrofolato reduttasi

I chinazolinoni sono composti eterociclici azotati che, insieme alle chinazoline, rappresentano degli importanti farmacofori in possesso di un ampio spettro di proprietà biologiche tra cui quella antitumorale. Recentemente sono stati riportati in letteratura dei derivati 4-chinazolinonici in grado di inibire in vitro l’enzima diidrofolato reduttasi (DHFR) con IC50 comprese tra 0.4 e 1.0 µM [1]. Allo scopo di progettare la sintesi di nuovi potenziali inibitori della DHFR, è stato condotto uno studio di modellistica molecolare considerando tale enzima come biotarget. Tale studio ha portato alla selezione di 42 nuovi derivati 4-chinazolinonici (Figura 1). Attualmente, sono stati sintetizzati 2…

NUOVI DERIVATI 2-ACETAMMIDOBENZAMMIDICI: ATTIVITÀ ANTIPROLIFERATIVA E POSSIBILE MECCANISMO DI AZIONE

Le cinnammido benzammidi rappresentano una classe di sostanze biologicamente attive di grande interesse farmaceutico. Nonostante siano state descritte per svariate attività biologiche, nessun dato è stato riportato sulla loro attivita antitumorale. Inizialmente una serie di 2-cinammidobenzammidi variamente sostituite sono state sintetizzate e valutate per la loro attività antiproliferativa. Partendo dal derivato risultato più attivo, il 2-cinnammido-5-iodobenzammide, che ha mostrato una percentuale di inibizione della crescita sulle K562 del 74% a 10μM, sono stati sintetizzati una serie di derivati al fine di approfondirne la SAR.I composti così ottenuti sono risultati attivi nei confronti …

Upper respiratory tract infections in children: From case history to management

Respiratory tract infections are the most common diseases in childhood. The respiratory tract, widely branched system of ducts, is particularly exposed to the action of microorganisms transmitted by air from here the high frequency of infections they face especially in the first years of life. It is usual distinguish: upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI). In particular, in infections of the upper airways, the inflammatory process, result of the interaction between microbes and the immune response, can be localized to the mucosa of the nose or sinuses (common cold and sinusitis), or the pharynx or larynx (pharyngotonsillitis and laryngitis) …

Corrigendum to “Effects of 8-OH-DPAT on open field performance of young and aged rats prenatally exposed to diazepam: a tool to reveal 5-HT1A receptor function”

CCDC 831724: Experimental Crystal Structure Determination

Related Article: B.Maggio, D.Raffa, M.V.Raimondi, F.Plescia, M.L.Trincavelli, C.Martini, F.Meneghetti, L.Basile, S.Guccione, G.Daidone|2012|Eur.J.Med.Chem.|54|709|doi:10.1016/j.ejmech.2012.06.028