Exploring regulation and function of dopamine D3 receptors in alcohol use disorder. A PET [11C]-(+)-PHNO study

Preclinical studies support an important role of dopamine D3 receptors (DRD3s) in alcohol use disorder (AUD). In animals, voluntary alcohol consumption increases DRD3 expression, and pharmacological blockade of DRD3s attenuates alcohol self-administration and reinstatement of alcohol seeking. However, these findings have yet to be translated in humans. This study used positron emission tomography (PET) and [¹¹C]-(+)-PHNO to compare receptor levels in several dopamine D2 receptor (DRD2) and DRD3 regions of interest between AUD subjects in early abstinence (n = 17; 6.59 ± 4.14 days of abstinence) and healthy controls (n = 18). We recruited non-treatment seeking subjects meeting DSM-5 criteria for AUD. We examined the relationship between DRD2/3 levels and both alcohol craving and alcohol motivation/wanting, using a cue reactivity procedure and an intravenous alcohol self-administration (IVASA) paradigm, respectively. [¹¹C]-(+)-PHNO binding levels in AUD subjects were significantly lower than binding in HCs when looking at all DRD2/3 ROIs jointly (Wilk’s Λ = .58, F(6,28) =3.33, p = 0.013, η²_p = 0.42), however there were no region-specific differences. Binding values demonstrate −12.3% and −16.1% lower [¹¹C]-(+)-PHNO binding in the SMST and SN respectively, though these differences did not withstand Bonferroni corrections. There was a positive association between [¹¹C]-(+)-PHNO binding in the SN (almost exclusively reflective of DRD3) and alpha (lower values reflect higher alcohol demand) in the APT after Bonferroni corrections (r = 0.66, p = 0.0080). This demonstrates that AUD subjects with lower DRD3 levels in the SN exhibit increased demand for alcohol. These results replicate previous findings demonstrating reduced DRD2/3 levels while also supporting a lack of DRD3 upregulation and potential downregulation in early abstinent AUD. Furthermore, the finding that binding in the SN is associated with alcohol demand warrants further examination.Subject terms: Neurotransmitters, Addiction, Translational research     

Large mass arising from the tongue as an initially and sole manifestation of Kaposi sarcoma

We report a 30- year-old Iranian woman presenting with a red to yellowish, well demarcated, painless exophytic and lobulated mass originating from the right hand side of the tongue. An excisional biopsy was obtained and it was diagnosed histopathologically as Kaposi's sarcoma by detecting atypical spindle cells with rare mitoses delineating blood-filled vascular slits.     

Mast cells and COPD

The pathogenesis of chronic obstructive pulmonary disease (COPD) is based on the innate and adaptive inflammatory immune response to the inhalation of toxic particles and gases. Although tobacco smoking is the primary cause of this inhalation injury, many other environmental and occupational exposures contribute to the pathology of COPD. The immune inflammatory changes associated with COPD are linked to a tissue-repair and -remodeling process that increases mucus production and causes emphysematous destruction of the gas-exchanging surface of the lung. The common form of emphysema observed in smokers begins in the respiratory bronchioles near the thickened and narrowed small bronchioles that become the major site of obstruction in COPD. The inflamed airways of COPD patients contain several inflammatory cells including neutrophils, macrophages, T lymphocytes, and dendritic cells. The relative contribution of mast cells to airway injury and remodeling is not well documented. In this review, an overview is given on the possible role of mast cells and their mediators in the pathogenesis of COPD. Activation of mast cells and mast cell signaling in response to exposure to cigarette smoke is further discussed.     

Effects of apple juice on risk factors of lipid profile, inflammation and coagulation, endothelial markers and atherosclerotic lesions in high cholesterolemic rabbits

Background  

Atherosclerosis which results from gradual deposition of lipids in medium and large arteries is a leading cause of mortality worldwide. The objective of this study was to determine the effect of apple juice on some risk factors of atherosclerosis and on the development of atherosclerosis in rabbits fed a high-cholesterol diet.     

Preclinical evaluation of [99mTc/EDDA/tricine/HYNIC0, 1-Nal3, Thr8]-octreotide as a new analogue in the detection of somatostatin-receptor-positive tumors

PURPOSE: Radiolabeled somatostatin analogues are important tools for the in vivo localization and targeted radionuclide therapy of somatostatin-receptor-positive tumors. The aim of this study was to evaluate a new somatostatin analogue designed for the labeling with (99m)Tc: [6-hydrazinopyridine-3-carboxylic acid (HYNIC(0)), 1-Nal(3), Thr(8)]-octreotide ([HYNIC]-NATE), using ethylenediamine-N,N'-diacetic acid (EDDA) and tricine as coligands. METHODS: Synthesis was preformed on a solid phase using a standard Fmoc strategy. Labeling with (99m)Tc was performed at 100 degrees C for 10 min using SnCl(2) as a reductant. Radiochemical analysis involved ITLC and high-performance liquid chromatography methods. Peptide conjugate affinity was determined in AR4-2J cell membranes. The internalization and externalization rates were studied in sstr(2)-expressing AR4-2J cells. Biodistribution of radiopeptide was studied in rats bearing the AR4-2J tumor. RESULTS: Radiolabeling was performed at high specific activities, and radiochemical purity was >95%. Peptide conjugate showed high affinity binding for sstr(2). The radioligand showed a moderate and specific internalization into AR4-2J cells (14.13+/-0.61% at 4 h). In animal biodistribution studies, a receptor-specific uptake of radioactivity was observed in somatostatin-receptor-positive organs. After 4 h, uptake in the AR4-2J tumor was 1.33+/-0.23%ID/g (percentage of injected dose per gram of tissue). CONCLUSION: These data show that [(99m)Tc/EDDA/tricine/HYNIC]-NATE is a specific radioligand for the somatostatin-receptor-positive tumors and is a suitable candidate for clinical studies.     

Liver histopathology and an in-house indirect ELISA method for the diagnosis of bovine fasciolosis

Tropical fasciolosis is regarded as one of the most important helminth infections of ruminants in Asia and Africa. Throughout most of its geographical range, Fasciola gigantica is of great importance as a parasite in cattle and buffalo. Fasciolosis diagnosis, due to low sensitivity of the coprological diagnostic method has been challenging for a long period. In this study, an in-house indirect enzyme-linked immunosorbent assay (iELISA) method; one of the most sensitive tests in this regard, using excretion–secretory (ES Ag) and Crude (Cr Ag) antigens and liver histopathology of F. gigantica were described for diagnosis of fasciolosis in cattle. For this purpose, the sera and liver specimens of slaughtered cattle were collected and their liver examined macroscopically and microscopically for infestation to fasciolosis. Sera from two groups of cattle, one infected with fasciolosis (n?=?50) and the other non-infected with fasciolosis (n?=?50), were used in the iELISA test; grouping based on histopathology results. All sera were tested by an in-house iELISA using optimum concentration of antigens. The sensitivity, specificity, accuracy, positive and negative predictive values of iELISA with ES Ag was 88%, 80%, 85%, 81%, and 87%, respectively, and with Cr Ag was 90%, 74%, 82%, 76%, and 88%, respectively. In conclusion, there was a good correlation between these two diagnostic tests of fasciolosis although iELISA using ES Ag was more closely correlated with the histopathology findings and could be regarded as a rapid diagnostic method in bovine fasciolosis.     

3D bio-printing technology for body tissues and organs regeneration

In the last decade, the use of new technologies in the reconstruction of body tissues has greatly developed. Utilising stem cell technology, nanotechnology and scaffolding design has created new opportunities in tissue regeneration. The use of accurate engineering design in the creation of scaffolds, including 3D printers, has been widely considered. Three-dimensional printers, especially high precision bio-printers, have opened up a new way in the design of 3D tissue engineering scaffolds. In this article, a review of the latest applications of this technology in this promising area has been addressed.     

Fabrication of polyhydroxybutyrate (PHB)/γ-Fe2O3 nanocomposite film and its properties study

Magnetic separation has numerous advantages in isolating cancerous and normal cells used in the diagnosis and treatment sectors. Here, we produced magnetic nanocomposite films made of polyhydroxybutyrate (PHB)/magnetite nanoparticles (γ-Fe₂O₃), and the properties of the films by SEM, TEM, FTIR, DMTA, contact angle, and cellular analyses were investigated. The microscopic images showed uniform distribution of γ-Fe₂O₃ magnetic nanoparticles in polymeric matrix. The chemical bounds between magnetic nanoparticles and polymeric matrix demonstrated using the FTIR spectrophotometer. The DMTA and contact angle results indicated an increase in the glass transition temperature and hydrophilic properties of nanocomposites is achieved by increasing the magnetic nanoparticles amount in polymer matrix. The cellular results were showed that adhesion of cancer cells compared to normal cells was significantly enhanced by the induction of a magnetic field. These nanocomposite films can be used as a substrate for cellular adhesion and separation processes.