Dual inhibitory action of trazodone on dorsal raphe serotonergic neurons through 5-HT1A receptor partial agonism and α1-adrenoceptor antagonism

Trazodone is an antidepressant drug with considerable affinity for 5-HT1A receptors and α1-adrenoceptors for which the drug is competitive agonist and antagonist, respectively. In this study, we used cell-attached or whole-cell patch-clamp recordings to characterize the effects of trazodone at somatodendritic 5-HT1A receptors (5-HT1AARs) and α1-adrenoceptors of serotonergic neurons in rodent dorsal raphe slices. To reveal the effects of trazodone at α1-adrenoceptors, the baseline firing of 5-HT neurons was facilitated by applying the selective α1-adrenoceptor agonist phenylephrine at various concentrations. In the absence of phenylephrine, trazodone (1-10 μM) concentration-dependently silenced neurons through activation of 5-HT1AARs. The effect was fully antagonized by the selective 5-HT1A receptor antagonist Way-100635. With 5-HT1A receptors blocked by Way-100635, trazodone (1-10 μM) concentration-dependently inhibited neuron firing facilitated by 1 μM phenylephrine. Parallel rightward shift of dose-response curves for trazodone recorded in higher phenylephrine concentrations (10-100 μM) indicated competitive antagonism at α1-adrenoceptors. Both effects of trazodone were also observed in slices from Tph2-/- mice that lack synthesis of brain serotonin, showing that the activation of 5-HT1AARs was not mediated by endogenous serotonin. In whole-cell recordings, trazodone activated 5-HT1AAR-coupled G protein-activated inwardly-rectifying (GIRK) channel conductance with weak partial agonist efficacy (~35%) compared to that of the full agonist 5-CT. Collectively our data show that trazodone, at concentrations relevant to its clinical effects, exerts weak partial agonism at 5-HT1AARs and disfacilitation of firing through α1-adrenoceptor antagonism. These two actions converge in inhibiting dorsal raphe serotonergic neuron activity, albeit with varying contribution depending on the intensity of α1-adrenoceptor stimulation

Foreign bodies in the upper airways: the experience of two Italian hospitals

OBJECTIVE: To study the pattern of foreign bodies in the upper airways as emerging from the hospital records in the Bologna and Siena hospitals in Italy 1997-2002. METHODS: A retrospective review of hospital records was performed using a standardized protocol. All injuries with ICD9 (International Classification of Diseases, 9'h revision) codes ranging from 931 to 934 which occurred in children age 0-14 were considered for the database. RESULTS: One hundred ninety seven patients were included in the database with a diagnosis of Foreign Bodies (FB) over the study period, 78 with ICD931, 105 with ICD932, 12 with ICD933 and 2 with ICD934 discharge diagnosis. Of the 197 patients, 51.90% of the patients were males and the 48.10% were female. Median age was 4 (2, 6). At the moment of the injury, the child was eating (11%), playing (83%) or studying (4%) or cleaning ears (2%). The child was supervised by an adult in doing his/her activities at the moment of injury in the 84.2% of the cases. The child reached the hospital using always private transport (100%), never by using an emergency transport (0%). Most commonly, FB were extracted in ambulatory (95.4%), more rarely using an endoscopic procedure (4.1%), and never using surgery. Hospitalization was required in the 0.5% of cases (1). CONCLUSIONS: Our study showed the substantial epidemiological similarity of the Italian data with the experience of other center in the world. The burden of chocking was very limited in our country, as proven by the limited access to emergency and more invasive procedures. Nevertheless, some consideration can be made from the preventive point of view. Quite surprisingly, the majority of injuries occurred under the supervision of an adult in playing or recreational activities

Foreign bodies in the upper airways: the experience of two Italian hospitals

OBJECTIVE: To study the pattern of foreign bodies in the upper airways as emerging from the hospital records in the Bologna and Siena hospitals in Italy 1997-2002. METHODS: A retrospective review of hospital records was performed using a standardized protocol. All injuries with ICD9 (International Classification of Diseases, 9'h revision) codes ranging from 931 to 934 which occurred in children age 0-14 were considered for the database. RESULTS: One hundred ninety seven patients were included in the database with a diagnosis of Foreign Bodies (FB) over the study period, 78 with ICD931, 105 with ICD932, 12 with ICD933 and 2 with ICD934 discharge diagnosis. Of the 197 patients, 51.90% of the patients were males and the 48.10% were female. Median age was 4 (2, 6). At the moment of the injury, the child was eating (11%), playing (83%) or studying (4%) or cleaning ears (2%). The child was supervised by an adult in doing his/her activities at the moment of injury in the 84.2% of the cases. The child reached the hospital using always private transport (100%), never by using an emergency transport (0%). Most commonly, FB were extracted in ambulatory (95.4%), more rarely using an endoscopic procedure (4.1%), and never using surgery. Hospitalization was required in the 0.5% of cases (1). CONCLUSIONS: Our study showed the substantial epidemiological similarity of the Italian data with the experience of other center in the world. The burden of chocking was very limited in our country, as proven by the limited access to emergency and more invasive procedures. Nevertheless, some consideration can be made from the preventive point of view. Quite surprisingly, the majority of injuries occurred under the supervision of an adult in playing or recreational activities

Geoelectrical Subsurface Characterization for Foundation Purposes in the College of Agricultural Sciences (CAS) Campus, Ebonyi State University, Abakaliki, Southeastern Nigeria

The study area is underlain by shales and volcanoclastics with subordinate lenses of sandstones and sandy limestone (Abakaliki Formation) of the Albian Asu River Group, southeastern Nigeria. Geophysical investigation was carried out at the College of Agricultural Sciences (CAS) Campus, Ebonyi State University (EBSU) to determine the structural competence of the subsurface geological strata for building construction and other foundation purposes, using vertical electrical sounding (VES) survey technique of the electrical resistivity method. From the result of the survey, two major zones have been established within the study area for building construction purposes. Zone A comprises of areas around the catholic church building, EBSU primary school up to the school of post graduate studies, while zone B  is made up of areas around the EBSU secondary school, proposed student centre up to the main entrance gate which led to the Ogoja road. Zone A has been recommended for bungalows and other forms of low rising buildings, while zone B has been recommended for storey buildings and other heavy engineering structures. Overburden thickness for the two zones ranges from 1.3 m to 2.7 m, and 0.6 m to 2.7 m for zones A and B respectively. The cracks on walls of the buildings within the campus have been attributed to either the inability of the engineers to dig the foundation to the required depth or the construction of heavier structures on very weak subsurface layers which triggered off movement. Keywords: Geoelectrical, Characterization, Foundation, Ebonyi State University, Nigeria

Polymorphic post-transplant lymphoproliferative disorder in a gilt

N.A. (case report, no abstract

Normothermic and hypothermic oxygenated perfusion for donation after circulatory death in kidney transplantation: Do we pay higher risk of severe infection after transplantation?: A case report

Background: Normothermic and hypothermic oxygenated perfusion for donation after circulatory death in kidney transplantation are becoming popular in Italy, with the purpose of reducing the risk of primary non function and delayed graft function due to the prolonged warm ischemia time. Potential complications related to these procedures are currently under investigation and are continuously emerging with the increasing experience. Post-operative infections - in particular graft arteritis - are a rare complication but determine high risk of mortality and of graft loss. The acute onset of the arterial complications makes it very difficult to find an effective treatment, and early diagnosis is crucial for saving both patient and graft. Prevention of such infections in this particular setting are advisable. Case presentation: We present a patient with an acute arterial rupture after transplantation of a DCD graft treated in-vivo hypothermic oxygenated perfusion. The cause was a severe arteritis of the renal artery caused by Candida krusei and Pseudomonas aeruginosa. We discussed our treatment and we compared it to the other reported series. Conclusion: Fungal infections in DCD transplant may be treacherous and strategies to prevent them should be advocated

Exploring the Evidence for Broad-Spectrum Effectiveness of Perampanel: A Systematic Review of Clinical Data in Generalised Seizures.

BACKGROUND: The effectiveness of adjunctive perampanel has not been systematically assessed in seizure types other than its approved indications of focal seizures and primary generalised tonic-clonic seizures (PGTCS) in idiopathic generalised epilepsies (IGEs). OBJECTIVE: We aimed to identify and review available evidence on outcomes with perampanel in generalised seizures and epilepsies to examine its potential as a broad-spectrum anti-seizure medication. METHODS: Bibliographic databases of publications, clinical trials, and conference abstracts were searched up to August 2020 to identify studies reporting seizure or safety outcomes in patients of any age, with any type of epilepsy-associated generalised seizures treated with perampanel. Data extracted from selected records were tabulated by seizure type and syndrome, and analysed qualitatively (PROSPERO protocol CRD42020201564). RESULTS: Ninety-one reports met inclusion criteria and were selected: 15 reports of 1 randomised controlled trial (RCT), 8 reports of 4 non-randomised interventional studies, 37 reports of observational studies, 21 case reports and 10 systematic reviews and meta-analyses. Extracted data included 359 patients with PGTCS of any aetiology, 251 with myoclonic seizures, 112 with absence seizures, 50 with tonic seizures and 32 children with epileptic spasms. The most commonly reported epilepsy type was IGE (N = 378) and the most common syndromes were juvenile myoclonic epilepsy (N = 92), progressive myoclonic epilepsies (N = 59) and absence epilepsies (N = 43). The RCT provided Class I evidence of the efficacy and tolerability of adjunctive perampanel for PGTCS in patients aged ≥ 12 years with IGE. Data from other studies provides weaker (observational) evidence of its effectiveness in multiple generalised seizure types, including myoclonic, absence and tonic seizures. There were no patterns suggesting seizure worsening or aggravation in any seizure or epilepsy type. CONCLUSIONS: The identified studies suggest the potential of perampanel as a broad-spectrum antiseizure medication. Much of the available data, however, come from non-randomised, non-controlled studies and are open to high risk of bias. Further studies are warranted to provide more robust evidence