Six-month humoral response to BNT162b2 mRNA COVID-19 vaccine in people with multiple sclerosis treated with natalizumab

Neurological Sciences - Few studies investigated the immune response to SARS-CoV-2 vaccine in patients with multiple sclerosis (pwMS) treated with natalizumab (NTZ) and found a short-term efficient...     

Screening of PRKAR1A and PDE4D in a Large Italian Series of Patients Clinically Diagnosed With Albright Hereditary Osteodystrophy and/or Pseudohypoparathyroidism

The cyclic adenosine monophosphate (cAMP) intracellular signaling pathway mediates the physiological effects of several hormones and neurotransmitters, acting by the activation of G‐protein coupled receptors (GPCRs) and several downstream intracellular effectors, including the heterotrimeric stimulatory G‐protein (Gs), the cAMP‐dependent protein kinase A (PKA), and cAMP‐specific phosphodiesterases (PDEs). Defective G‐protein–mediated signaling has been associated with an increasing number of disorders, including Albright hereditary osteodistrophy (AHO) and pseudohypoparathyroidism (PHP), a heterogeneous group of rare genetic metabolic disorders resulting from molecular defects at the GNAS locus. Moreover, mutations in PRKAR1A and PDE4D genes have been recently detected in patients with acrodysostosis (ACRDYS), showing a skeletal and endocrinological phenotype partially overlapping with AHO/PHP. Despite the high detection rate of molecular defects by currently available molecular approaches, about 30% of AHO/PHP patients still lack a molecular diagnosis, hence the need to screen patients negative for GNAS epi/genetic defects also for chromosomal regions and genes associated with diseases that undergo differential diagnosis with PHP. According to the growing knowledge on Gsα‐cAMP signaling‐linked disorders, we investigated our series of patients (n = 81) with a clinical diagnosis of PHP/AHO but negative for GNAS anomalies for the presence of novel genetic variants at PRKAR1A and PDE4D genes. Our work allowed the detection of 8 novel missense variants affecting genes so far associated with ACRDYS in 9 patients. Our data further confirm the molecular and clinical overlap among these disorders. We present the data collected from a large series of patients and a brief review of the literature in order to compare our findings with already published data; to look for PRKAR1A/PDE4D mutation spectrum, recurrent mutations, and mutation hot spots; and to identify specific clinical features associated with ACRDYS that deserve surveillance during follow‐up. © 2016 American Society for Bone and Mineral Research.     

Exosomes in human atherosclerosis: An ultrastructural analysis study

Cell-to-cell communication, or signaling, is absolutely essential in orchestrating the activities of cells in multicellular organisms, to grow, develop, detect environmental changes and compensate for them in an internal, coordinated fashion. In the last few years, a considerable amount of new data have demonstrated the occurrence of a sophisticated intercellular signaling pathway based on the release of specialized vesicular structures, called exosomes, whose secretion appears to be regulated by various natural and experimental stimuli, physiological states, and disease processes. In the cardiovascular system, the study of exosomes is still in its infancy. Here, we aim to provide the first ultrastructural evidence for the presence of exosomes in human atherosclerotic plaque. We demonstrate by means of transmission electron microscopy that both lesional smooth muscle cells and endothelial cells are able to generate these membraneous microvesicles within specific compartments of the cell, called multivesicular bodies. Notably, in our series no signs of apoptosis have been detected in vascular cells secreting exosomes and no evidence of calcification has been observed associated with these structures in the extracellular space. Our results suggest the possible existence of a new mechanism of intercellular communication in the plaque milieu.     

Ultrastructural evidence of Tropheryma whippelii in PAS-negative granulomatous lymph nodes

The presence of Tropheryma whippelii was demonstrated in the PAS-negative mesenteric granulomatous lymph nodes of a patient affected by Whipple disease. Ultrastructurally a few bacteria, enclosed by a membrane characteristic of Tropheryma whippelii, were found in the extracellular spaces and remnants of bacteria were found in the phagocytic vacuoles of macrophages. The scarce number of bacilli, probably due to the fact that the disease was at an initial phase, could explain the absence of PAS positivity. This case confirms the role of the electron microscopy in the diagnosis of Whipple disease, especially for extra-intestinal lesions and at the initial phase of the disease, when the characteristic PAS-positive macrophages can be absent.     

Influence of Dissolution Media and Presence of Alcohol on the In Vitro Performance of Pharmaceutical Products Containing an Insoluble Drug

The purpose of this investigation is to determine how the dissolution media may influence the release rate of an insoluble drug in in vitro conditions. Some oral dosage forms containing ibuprofen, a molecule that shows pH-dependent solubility, are tested. They are evaluated in different media to simulate the gastrointestinal transit at paddle rotation speeds of 50 and 100 rpm. Moreover, the potential effect of different ethanol concentrations on drug release is tested. The dissolution profiles of the tablets show a similar behavior in water (pH 1.0) and phosphate buffer (pH 4.5) where the 2 doses are not completely dissolved. The soft capsules show a different behavior: a certain amount of ibuprofen, which is in solution inside the capsule, reprecipitates in water and in the pH 4.5 buffer. Instead, ibuprofen dissolves rapidly in the pH 6.8 buffer from all the formulations. In the water-ethanol solutions, the dissolution curves show a valuable increase in the drug dissolved at higher ethanol concentrations.     

Peri-implant bone regeneration with calcium sulfate: a light and transmission electron microscopy case report

BACKGROUND: Calcium sulfate is a simple, biocompatible material with a very long, safe clinical history in several different fields of medicine. It is a rapidly resorbing material that leaves behind calcium phosphate lattice, which promotes bone regeneration. OBJECTIVE: The aim of this study was a histological and ultrastructural evaluation of the tissues in a peri-implant site regenerated with calcium sulfate. MATERIALS AND METHODS: The specimens were processed for observation under light and transmission electron microscopes. RESULTS: In light microscopy, trabecular bone was present. No remnants of calcium sulfate were present. Transmission electron microscopy showed, in the areas of the interface with the implant surface, features of mature bone with many osteocytes. An amorphous layer and/or osteoid seam separated this mature bone from the metal surface. CONCLUSION: The results confirm the high biocompatibility and rapid resorption of calcium sulfate.     

Human peri-implant bone response to turned and oxidized titanium implants inserted and retrieved after 2 months

PURPOSE: The aim of this study was to evaluate the influence of oxidized surface on bone-to-implant contact percentage (BIC%) as well as the bone density within the threads area (BD%) in human bone after 2 months of unloaded healing. MATERIALS: Seven subjects (mean age 45.57 +/- 10.45 years) received 2 micro-implants each during conventional implant surgery in the posterior maxilla. The implants that presented turned and oxidized surfaces served as control and test, respectively. After the healing period, the implants and the surrounding tissue were removed and prepared for ground sectioning and analysis. RESULTS: Two turned implants were found to be clinically unstable at the time of retrieval. Histometric evaluation showed that the mean of BIC% was 17.40 +/- 14.16% and 32.19 +/- 15.68% to turned and oxidized surfaces, respectively. The BD% was 22.13 +/- 19.06% for turned surface and 50.40 +/- 18.35% for oxidized surface. CONCLUSION: The histologic data from this preliminary study suggest that the oxidized micro-implants surface presented better mean values of BIC% and BD% than turned micro-implants after a short healing time.     

Microvessel density in sinus augmentation procedures using anorganic bovine bone and autologous bone: 3 months results

PURPOSE: This study was an immunohistochemical evaluation of microvessel density (MVD) in sinus augmentation procedures with autologous bone and anorganic bone (Bio-Oss). MATERIALS AND METHODS: Twenty-four patients (14 men and 10 women - mean age of 48 years with a range from 34 to 53 years) participated in this study. All the patients presented a maxillary partial unilateral edentulism involving the premolar/molar areas, with a residual alveolar ridge height of about 4 to 5 mm. Twelve patients received sinus augmentation procedures with 100% autologous bone; 100% Bio-Oss was used in the other 12 patients. Endosseous implants were inserted after a mean period of 3 months. As control, the portions of preexisting subantral bone were used. The mean value of the MVD in control bone was 23.4 +/- 1.3. The mean value of the MVD in the sinuses augmented with autologous bone was 29.0 +/- 2.4. The mean value of the MVD in the sinuses augmented with Bio-Oss was 23.8 +/- 2.2. RESULTS: The statistical analysis showed that the differences of the MVD between control bone and sinuses augmented with Bio-Oss were not statistically significant (P = 0.52), while the difference of the MVD between sinuses augmented with autologous bone and those augmented with Bio-Oss was statistically significant (P = 0.0008). CONCLUSIONS: Autologous bone may act not only as a passive filling material in bone defects but may also release osteogenic growth factors; and particles of autologous bone seem to contain vital osteoprogenitor cells.     

Maspin expression in oral squamous cell carcinoma

Maspin (mammary serine protease inhibitor) is a member of the serpin superfamily of protease inhibitors and it has a role as a tumor suppressor. Maspin has been reported to be important in processes relevant to tumor growth and metastasis such as cell invasion, angiogenesis, and apoptosis. A high expression of maspin was correlated with better rates of survival and absence of nodal metastases in head and neck squamous cell carcinoma. In contrast, some studies have shown that maspin overexpression is correlated with a poor prognosis in pancreatic and ovarian cancers and in lung adenocarcinoma. The aim of this study was an immunohistochemical evaluation of the maspin expression in oral squamous cell carcinoma and thus 89 patients were evaluated. Maspin expression in oral squamous cell carcinoma was significantly associated with the tumor differentiation grade (chi test: P = 0.0318) and the lymph node status (chi test: P < 0.005), but not with the tumor stage (chi test: P = 0.666). Metastatic involvement of lymph nodes was observed more frequently in maspin-negative cases than in tumors with more than 5% of positive cells (P = 0.0024). The present results confirm that maspin expression predicts a better prognosis in oral squamous cell carcinoma and that maspin probably plays a role in tumor progression.