Stefano Tonini

Intestinal dysmotility and enteric neurochemical changes in a Parkinson's disease rat model

Gastrointestinal disorders, constipation in particular, are the most common non-motor dysfunctions affecting Parkinsons disease (PD) patients. We have previously reported that rats bearing unilateral nigrostriatal lesion caused by 6-hydroxydopamine (6-OHDA) stereotaxic injection develop severe constipation together with a region-specific decrease of neuronal nitric oxide synthase (nNOS) in enteric neurons of the lower intestinal tract. Here, we extend these observations on other enteric neuronal subpopulations, investigating also the propulsive activity of isolated colonic specimens. Four weeks post 6-OHDA injection, lesioned rats showed a significant increase of vasoactive intestinal polypeptide (VIP) concomitant with the reduced expression of nNOS in the myenteric plexus of distal ileum and proximal colon; in particular VIP increased in a subpopulation of neurons actively expressing nNOS. On the other hand, choline acetyltransferase (ChAT) was not modified in any of the intestinal segments analyzed. Interestingly, we found a reduced expression of dopamine receptor type 2 (D2R) in proximal (-66.8%) and distal (-54.5%) colon, together with reduced peristalsis efficiency (decrease in intraluminal pressure and frequency of peristaltic events) in the 6-OHDA-lesioned rats. The selective depletion of dopaminergic nigrostriatal neurons is associated with changes in the expression of enteric inhibitory neurotransmitters, as well as of the D2R in intestinal specific regions. Moreover, 6-OHDA-lesioned rats demonstrated altered colon propulsive activity referable to the D2R decrease. Our findings unveil subtle mechanisms underlying the enteric neurochemical plasticity events evoked by disruption of the normal brain-gut cross-talk, giving a peculiar point of view on the pathophysiology of the severe constipation that frequently affects PD patients.

Irritant vocal cord dysfunction and occupational bronchial asthma: differential diagnosis in a health care worker

OBJECTIVES Vocal cord dysfunction (VCD) is an uncommon respiratory disease characterized by the paradoxical adduction of vocal cords during inspiration, that may mimic bronchial asthma. The pathogenesis of VCD has not been clearly defined but it is possible to recognize non-psychologic and psychologic causes. The majority of patients are female but, interestingly, a high incidence of VCD has been documented in health care workers. A misdiagnosis with asthma leads to hospitalisation, unnecessary use of systemic steroids with related adverse effects, and sometimes tracheostomy and intubation. In a subset of VCD patients, the disease can be attributed to occupational or environmental exposure to inhaled irritants. MATERIALS AND METHODS We report the case of a 45-year-old woman, working as a nurse, who complained of wheezing, cough, dyspnoea related to inhalation of irritating agents (isopropylic alcohol, formaldehyde, peracetic acid). She underwent chest radiography, pulmonary function assessment both in the presence and in the absence of symptoms, bronchial provocation with methacholine and bronchodilation test with salbutamol to recognize asthmas features, allergy evaluation by skin prick tests and patch tests and video-laryngoscopy. RESULTS VCD diagnosis was made on the basis of video-laryngoscopy, that visualized the paradoxical motion of the vocal cords during symptoms, in the absence of other pathologic processes. CONCLUSIONS This case fulfils the proposed criteria for the diagnosis of irritant VCD (IVCD). This is the first report of VCD onset following exposure to several irritants: formaldehyde, glutaraldehyde, sopropylic alcohol, peracetic acid-hydrogen peroxide mixture. These substances are used as cleaning and antiseptic agents in healthcare settings and some ones can also be found in many indoor environments. A correct diagnosis is important both to give the appropriate treatment and for medical legal implications.

Return to Work After Coronary Angioplasty or Heart Surgery: A 5-Year Experience With the CardioWork Protocol

Objective:The “CardioWork” protocol, for work resumption after invasive heart procedures and subsequent cardiac rehabilitation, is presented. Methods:Over 5 years, 107 consecutive patients of working age were enrolled. Jobs were classified as multiples of basal metabolism according to the entity of physical strain. These data were integrated with instrumental evaluations to provide indications regarding time and modality of work resumption. Results:A total of 89.7% of patients resumed working. Other relevant findings include the correlation of time for work resumption with the kind of treatment and the task energy requirement; the earliness of return to work, even for older people and those performing heavy tasks; and the difficulty of work resumption for those who failed to restart work within 6 months. Conclusions:This study highlights the importance of a multidisciplinary rehabilitative approach to facilitate work resumption, adapting the work tasks to the changed psychophysical capabilities.

Adenosine A1 and A3 Receptor Agonists Inhibit Nonadrenergic, Noncholinergic Relaxations in the Guinea Pig Isolated Trachea

Background: Adenosine affects the tone and reactivity of airways by activating specific membrane receptors, named A₁, A_2a, A_2b and A₃. It affects cellular activities either directly by regulating membrane ion exchanges and polarization, or indirectly by modifying neurotransmitter release. Objectives: We assessed the effect of A₁ and A₃ receptor activation on electrically induced nonadrenergic, noncholinergic (NANC) relaxations in the guinea pig isolated trachea and the localization of A₁ and A₃ receptors in tracheal inhibitory neurons. Methods: NANC responses at 3 Hz were evaluat- ed in the presence of 2-chloro-N⁶-cyclopentyladenosine (CCPA), a selective A₁ agonist, and 2-chloro-N⁶-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (Cl-IB-MECA), a selective A₃ agonist, before and after the administration of 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a selective A₁ antagonist, or 9-chloro-2-(2-furanyl)-5-((phenylacetyl)amino[1,2,4]triazolo[1,5-c])quinazoline (MRS 1220), a selective A₃ antagonist, respectively. For immunohistochemistry, tissues were exposed to antibodies to HuC/D, a general neuronal marker, neuronal nitric oxide synthase (nNOS), and A₁ or A₃ adenosine receptors and processed by indirect immunofluorescence. Results: CCPA (10 nM–3 μM) inhibited NANC relaxations. DPCPX (10 nM) failed to antagonize the effect of CCPA, but inhibited per se NANC relaxations (range 0.1–100 nM). CCPA (10 nM–10 μM) contracted unstimulated tracheal preparations, an effect antagonized by 10 nM DPCPX, with a pK_B value of 8.43. Cl-IB-MECA (10 nM–3 μM) inhibited NANC relaxations through a mechanism antagonized by MRS 1220 (100 nM). A₁- and A₃-positive neurons containing nNOS were detected in tracheal sections. Conclusions: Enogenous adenosine may induce airway hyperresponsiveness by inhibiting NANC relaxations via A₁ and A₃ receptors.

Inhaled ammonium persulphate inhibits non-adrenergic, non-cholinergic relaxations in the guinea pig isolated trachea.

Background: Persulphates can act both as irritants and sensitizers in inducing occupational asthma. A dysfunction of nervous control regulating the airway tone has been hypothesized as a mechanism underlying bronchoconstriction in asthma. Objectives: It was the aim of this study to investigate whether inhaled ammonium persulphate affects the non-adrenergic, non-cholinergic (NANC) inhibitory innervation, the cholinergic nerve-mediated contraction or the muscular response to the spasmogens, carbachol or histamine, in the guinea pig epithelium-free, isolated trachea. Methods: Male guinea pigs inhaled aerosols containing ammonium persulphate (10 mg/m3 for 30 min for 5 days during 3 weeks). Control animals inhaled saline aerosol. NANC relaxations to electrical field stimulation at 3 Hz were evaluated in whole tracheal segments as intraluminal pressure changes. Drugs inactivating peptide transmission, nitric oxide synthase, carbon monoxide production by haem oxygenase-2 and soluble guanylyl cyclase were used to assess the involvement of various inhibitory neurotransmitters. Carbachol and histamine cumulative concentration-response curves were obtained. Results: In both groups, nitric oxide and carbon monoxide participated to the same extent as inhibitory neurotransmitters. In exposed animals, the tracheal NANC relaxations were reduced to 45.9 ± 12.1% (p < 0.01). The cholinergic nerve-mediated contractions to electrical field stimulation and the muscular response to histamine were not modified by ammonium persulphate exposure. The muscular response to carbachol was unaffected up to 1 µM. Conversely, the response to the maximal concentration of carbachol (3 µM) was increased (p < 0.01). Conclusion: Ammonium persulphate inhalation at high concentrations impairs the nervous NANC inhibitory control in the guinea pig airways. This may represent a novel mechanism contributing to persulphate-induced asthma.

Carpometacarpal subchondral cysts due to repetitive movements in shoemaker: A case report

ObjectivesSubchondral carpometacarpal cysts are classic and almost pathognomonic lesions found in workers using vibrating instruments over prolonged periods of time.Materials and MethodsWe present the case of a 53-year-old woman who worked for 30 years sewing shoe uppers, a task which required grasping firmly a pear-shaped handle awl and pushing it through the leather upper and the sole of the shoe, with combined flexion and supination movement of the wrist. After approximately 20 years of working, the patient noted gradual onset of paresthesias in the dominant (right) hand, with increasing difficulty in grasping the awl. Subsequent diagnosis of carpal tunnel syndrome was confirmed by electrophysiologic testing and its surgical release was performed. Nevertheless, hand pain, paresthesias and weakness persisted.ResultsUltrasound of the snuffbox tendons excluded DeQuervain tenosynovitis. Radiographic imaging of the symptomatic hand showed carpometacarpal subchondral cystic formations.ConclusionsIn addition to demonstrating the usefulness of radiographic imaging in patients with persistent hand pain post-carpal release, this case is important in illustrating that repetitive movements with high pressure over the palmar carpal area may cause bone cysts, even if the subjects do not use vibrating tools.

Analisi retrospettiva della prevalenza di complicanze correlate alle procedure di chemioembolizzazione intra-arteriosa epatica (TACE) nelle differenti classi di rischio

Transcatheter hepatic chemoembolization (TACE) is widely used in the treatment of unresectable hepatic tumors. Although considered relatively safe, TACE has been associated with several complications. The aim of this study was to determine the prevalence of complications and correlate them with some know risk factors. Between 2004 and 2009 we treated 155 patients (106 men and 49 women) with 297 sessions of TACE. 193 patients had primitive liver tumor and 104 had metastases from different primitivities. The patients were aged 49–86 years. TACE procedures were performed either with drug loaded microspheres (136 sessions with DCBead®; 124 with Hepasphere®) and with iodized oil (33 with Lipiodol®). The chemoterapeutic agent used was Epidoxorubicin in 217 sessions, Irinotecan in 30 and Oxaliplatin in 50. Our data showed that major complications occurred in 16.5% of patients. Specifically we found acute pancreatitis (2.7%), liver abscess (3%), cholecystistis (3.7%) and autoimmune thrombocytopenia (3.4%). Around 80 % of patients had postembolization syndrome that is not considered a complication but rather an expected outcome of embolotherapy. Complications occurred more frequently in diabetic than in non diabetic patients (26.7% vs 13.1%; p=0.006). Conversely we didn’t find any statistically significant differences according to the embolization agents used (Lipiodol® vs microspheres), the chemotherapic agent (Epidoxorubin vs Oxalplatin vs Irinotecan ), the age of the patients and the histology (primary vs metastatic tumors). All patients received antibiotic therapies before and after TACE; no statistically significant differences were found among the different classes of antibiotics used. Also no more complications were found with combined therapies (TACE+RFTA) than with TACE alone. Among the know risk factors only diabetes increases the prevalence of complications of TACE. TACE with Lipiodol® is more painful than drug loaded microspheres.