The Dopaminergic System in Peripheral Blood Lymphocytes: From Physiology to Pharmacology and Potential Applications to Neuropsychiatric Disorders

Besides its action on the nervous system, dopamine (DA) plays a role on neural-immune interactions. Here we review the current evidence on the dopaminergic system in human peripheral blood lymphocytes (PBL). PBL synthesize DA through the tyrosine-hydroxylase/DOPA-decarboxylase pathway, and express DA receptors and DA transporter (DAT) on their plasma membrane. Stimulation of DA receptors on PBL membrane contributes to modulate the development and initiation of immune responses under physiological conditions and in immune system pathologies such as autoimmunity or immunodeficiency. The characterization of DA system in PBL gave rise to a further line of research investigating the feasibility of PBL as a cellular model for studying DA derangement in neuropsychiatric disorders. Several reports showed changes of the expression of DAT and/or DA receptors in PBL from patients suffering from several neuropsychiatric disorders, in particular parkinsonian syndromes, schizophrenia and drug-or alcohol-abuse. Despite some methodological and theoretical limitations, these findings suggest that PBL may prove a cellular tool with which to identify the derangement of DA transmission in neuropsychiatric diseases, as well as to monitor the effects of pharmacological treatments

Effects of intra-VTA injection of neurotensin on local cerebral glucose utilization in the rat.

The [14C]2-deoxyglucose method was applied to measure the effects of the injection of neurotensin (7 microg) in the ventral tegmental area on local cerebral glucose utilization in the rat. Injection of neurotensin produced significant increases of glucose utilization in the shell of the nucleus accumbens and in the olfactory tubercle. These results indicate that stimulation of neurotensin receptors in the ventral tegmental area produces functional changes that are confined to the regions receiving mesolimbic projections within the rostral extended amygdaloid complex. These findings extend our understanding on the effects of neurotensin in the limbic system, with particular regard to reward pathways

Prodromal non-motor symptoms of Parkinson’s disease

The motor symptoms of Parkinson’s disease (PD), bradykinesia, muscular rigidity, and tremor depend upon degeneration of the dopaminergic neurons in the substantia nigra pars compacta. Recent neuropathological studies show that the Lewy bodies, the intraneuronal landmark of PD, accumulate in several neuronal cell types in the brain. An ascending gradient of pathological involvement, from the medulla oblongata to neocortical areas has been reported. Thus the original view of PD as a disease characterized by selective damage of the dopaminergic neurons in the mesencephalon should be updated into the concept of a severe multisystemic neurodegenerative disorder. Additionally, the neuropathological alterations outside the substantia nigra are soundly correlated with the non-motor symptoms of PD. As a result of these findings, interest is growing in the identification of prodromal non-motor symptoms of PD. Indeed, data from the literature suggest that autonomic disturbances, olfactory dysfunctions, depression and sleep disorders (in particular REM-sleep behavior disorder) may represent prodromal non-motor symptoms of PD. Several tests are available to detect most of these symptoms. Thus, the identification of prodromal non-motor symptoms may contribute to the precocious diagnosis of PD, and might be useful in the future to test the efficacy of neuroprotective agents

Meshed Dermal Sling for Prepectoral Breast Reconstruction

The best breast reconstruction solution after mastectomy remains a topic of wide debate. Recently, the focus in the field of implant-based reconstruction has been on the increasing indications for prepectoral reconstruction. This offers undoubted advantages over subpectoral reconstruction, ranging from better aesthetic results and patient comfort to a less invasive procedure that spares the pectoralis major muscle, reducing pain and postoperative recovery time. The dermal sling is a reconstructive variant introduced by Bostwick in the 1990s and is commonly used to complete the subpectoral pocket in one- or two-stage reconstruction, creating a dual-plane reconstruction. This method may be indicated after mastectomy for both therapeutic and prophylactic purposes. It can also be used for unilateral and bilateral reconstructions. We propose a new meshed dermal sling technique that allows complete prepectoral reconstruction without the use of acellular dermal matrix, thus reducing the cost of reconstruction. It also allows the indication for complete prepectoral reconstruction to be extended to patients with medium breast volume and grade 1 or 2 ptosis, without the need to use acellular dermal matrix or the pectoralis major muscle to complete the breast pocket

Lembo DIEP: applicazioni alternative alla ricostruzione mammaria e revisione della letteratura

L’introduzione di lembi basati sulle perforanti ha aumentato notevolmente le possibilità ricostruttive per il chirurgo plastico, sostituendo progressivamente l’utilizzo dei lembi miocutanei. Il lembo DIEP, in particolare, ha assunto un ruolo fondamentale nella ricostruzione mammaria, ma non solo: per le sue caratteristiche potrebbe, in casi selezionati, risultare un lembo ottimale nella ricostruzione di altri distretti corporei. Lo scopo di questo lavoro di tesi è quello di revisionare la letteratura internazionale e riportare l’esperienza dell’Azienda Ospedaliero Universitaria Pisana nell’utilizzo del lembo DIEP in distretti alternativi alla ricostruzione mammaria, descrivendo i potenziali vantaggi e suggerendo delle possibili indicazioni al suo utilizzo nei difetti dei tessuti molli

Cultura della rigenerazione: ricerca applicata, esperienze regionali (sezione "Mosaico Italia" della Rivista "Urbanistica Informazioni", n. 312/2023)

Cultura della rigenerazione: ricerca applicata, esperienze regionali (sezione "Mosaico Italia" della Rivista "Urbanistica Informazioni", n. 312/2023). La sezione, curata da Gianfranco Buttarelli e Antonio Cappuccitti, tratta i seguenti aspetti del dibattito ed esperienza urbanistica recenti riguardanti la cultura e la pratica della rigenerazione urbana: "La cultura della rigenerazione: ricerca applicata, esperienze regionali" (Gianfranco Buttarelli, Antonio Cappuccitti), "Rigenerare recuperando: i piani particolareggiati esecutivi del Comune di Aprilia" (Gianfranco Buttarelli, Ilaria Buttarelli), "Ricerca applicata e norme regionali nella cultura della rigenerazione urbana" (Antonio Cappuccitti), "Gli schemi di assetto, riferimento sistemico per tutti gli interventi di rigenerazione urbana" (Damiano Maurizio Sollami), "La rigenerazione urbana nel Lazio e la Lr 7/2017. Stato, criticità, riflessioni" (Francesco Rubeo)

Neuropharmacology and behavior in planaria: translations to mammals

Planarians are the simplest animals to exhibit a body plan common to all vertebrates and many invertebrates, characterized by bilateral rather than radial symmetry, dorsal and ventral surfaces, and a rostrocaudal axis with a head and a tail, including specialized sense organs and an aggregate of nerve cells in the head. Neurons in planarian more closely resemble those of vertebrates than those of advanced invertebrates, exhibiting typical vertebrate features of multipolar shape, dendritic spines with synaptic boutons, a single axon, expression of vertebrate-like neural proteins, and relatively low spontaneously generated electrical activity. Here we report the most relevant contribution to the knowledge of the neuropharmacology of planarians, with particular reference to the behavioral consequences of the exposure to drugs acting on neural transmission. Neurochemical and histochemical data indicate the presence of several neurotransmitter-receptor systems in planarians. Moreover, a variety of experimental studies characterized specific behavioral patterns of these animals following the exposure to drugs acting on neural transmission. There is also evidence of the interactions between discrete neurotransmitter-receptor systems in modulating behavior in planarians. Finally, the model has proved efficacy for investigating the neurotoxicology of the dopamine neurons, and for the initial screening of the neuroprotective potential of drugs. In conclusion, these findings indicate that interactions between discrete neurotransmitter-receptor systems occur very early along phylogeny, although they may have evolved from very fundamental behaviors, such as motor activity in planarian, to more complex and integrated functions in vertebrates

Thorned heart. Description of a near-fatal cardiac embolism after percutaneous Vertebroplasty

Cement extravasation is a rather common complication of vertebroplasty, which can be observed in up to 30-40% of patients undergoing this procedure, further associated with venous leakage occurring in up to 24% of cases. Pulmonary embolism may eventually develop once the cement migrates within the pulmonary artery, and is the most common complication of cement extravasation (involving ~4.6% of patients). Intra-cardiac cement embolism is considerably less frequent, but is a potentially fatal complication, mostly managed with cardiac surgery. We describe here a rare case of near-fatal cardiac cement embolism, with a large fragment perforating the right ventricle and reaching the pericardium, who presented to the Emergency Department (ED) for syncope. The patient, who displayed this severe complication after a vertebroplasty procedure performed for osteoporotic compression fracture, needed cardiac surgery

Cannabinoid-induced stimulation of motor activity in planaria by an opioid receptor-mediated mechanism

Planaria, the most primitive example of centralization and cephalization of the nervous system along phylogeny, shows specific stereotyped behavioral patterns following exposure to drugs acting on neural transmission. In this study, the authors investigated the effects of exposure to the synthetic cannabinoid receptor agonist WTN55212.2 on motor activity in planaria. WTN55212.2 produced dose-dependent stimulation of motor behavior. High doses of the drug caused stereotyped activities identical to those seen previously with opioid agonists. These effects were antagonized by coexposure to cannabinoid or opioid receptor antagonists. The results indicate that functional interactions between cannabinoid and opioid systems are highly conserved along phylogeny, at least at the behavioral level

Dopamine transporter immunoreactivity in peripheral blood mononuclear cells in amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a chronic progressive neuromuscular disorder of unknown etiology, characterized by weakness, muscle wasting, fasciculations, and increased reflexes, with conserved intellect and higher functions. The neuropathology of ALS is mostly confined to damage of the motor neurons in the cerebral cortex, some motor nuclei of the brainstem, and anterior horns of the spinal cord. However, there is evidence for the involvement of other neuronal systems in the disease. In particular, damage of the dopamine neurons has been shown by neurochemical and imaging studies in the brain and spinal cord of ALS patients. Recent reports suggest that peripheral blood mononuclear cells (PBMC) may represent a useful in vivo model to study neurochemical alterations that occur in neurodegenerative disorders. Here we demonstrate the significant reduction of dopamine transporter immunoreactivity in PBMC of patients affected by ALS with respect to healthy subjects. These results extend our knowledge of damage of the dopamine system in ALS to peripheral cells. Thus, the original concept of ALS as an isolated degeneration of motor neurons seems to extend to a more widespread understanding of the disease with involvement of other neuronal systems in the central as well as peripheral nervous system