A novel class of highly potent and selective A1 adenosine antagonists: structure-affinity profile of a series of 1,8-naphthyridine derivatives

A series of 1,8-naphthyridine derivatives (12-36), bearing a phenyl group in position 2 and various substituents in positions 4 and 7, were synthesized in an attempt to obtain potent, selective antagonists for the A1 adenosine receptor subtype. The compounds were tested to evaluate their affinity for A1 compared with A2A and A3 adenosine receptor subtypes. In binding studies in bovine brain cortical membranes, most of the compounds showed an affinity for A1 receptors in the low nanomolar range and two in the subnanomolar range with an interesting degree of A1 versus A2A and A3 selectivity. Comparison of the 4-substituted derivatives indicated that 4-OH substitution, with a 4-quinoid structure, causes an increase in the A1 and A2A affinity and generally also in A1 selectivity. The kind of substitution in position 7 can greatly modulate the affinity: the most interesting substituents in this position seemed to be electron-withdrawing groups; in particular the 7-chloronaphthyridine 25d showed a remarkable selectivity (A2A/A1 ratio of 670, A3/A1 ratio of 14,000) associated with a higher A1 affinity (Ki = 0.15 nM). NMR studies on these compounds 12-36 indicated that the 4-OH-substituted ones prefer the tautomer in which the oxygen in position 4 is in the quinoid form and the nitrogen in position 1 is protonated. Theoretical calculations are in agreement with the NMR data.     

Evaluation of efficacy and tolerability of K-FA fluocinolone acetonide tape

In order to assess the efficacy and tolerability of a fluocinolone acetonide tape (8 micrograms/cm2), 30 volunteer out-patients, 11 females and 19 males, mean age 43.4 years, affected by different kinds of dermatoses were treated. The tape was applied once or twice daily for an average period of 9.3 days. At the beginning and the end of the treatment, detailed dermatological and blood chemistry examinations were performed in all the patients. The clinical results were excellent for all the dermatoses treated. Itching at the site of application was reported by two patients and slight atrophy was observed in one patient. The patients' compliance was excellent. The blood chemistry tests showed no significant variation.     

Development of the cloacal bursa in the domestic fowl. I. An allometric and morphological study of the interfollicular surface epithelium (ISE)

The allometric relation applied between the body weight and the volume increment of the interfollicular surface epithelium (ISE) showed just one developmental stage during the period analysed (from 16d old embryos through 28 old d chicks). In this single allometric developmental stage the ISE growth is relatively more pronounced than that of the bursa as a whole due to profound cellular modifications which that epithelium undergoes from the primitive undifferentiated epithelial cells through goblet and prismatic cells. The latter could have an endocytic capability due to their primary and secondary lysosomes content. A possible cellular differentiation of the ISE during the histogenesis of the cloacal bursa is also discussed.     

Beyond Lockdown: The Potential Side Effects of the SARS-CoV-2 Pandemic on Public Health

Lockdowns to contain the spread of the SARS-CoV-2 have disrupted routines and behaviors, which could lead to a worsening of lifestyle and an increase in the burden of non-communicable diseases. This study aimed to describe the changes in physical activity, diet, alcohol drinking, and cigarette smoking during lockdown. A self-administered online survey addressing adults living in a province in northern Italy was advertised through websites and social media. Citizens could access the survey in anonymity from 4 May until 15 June 2020. A total of 1826 adults completed the survey, with a worsening of physical activity (35.1%), diet (17.6%), alcohol drinking (12.5%), and cigarette smoking (7.7%) reported. In contrast, 33.5% reported an improvement in diet, 12.6% in alcohol drinking, 5.3% in physical activity and 4.1% in cigarette smoking. Female sex, young adult age, suspension of work activity, and symptoms of psychological distress were the factors associated with a greater likelihood of change, which was frequently for the worse. Lockdown had an impact on lifestyle, with some net beneficial effects on diet and mostly negative effects on physical activity. Public health measures should be implemented to avoid long-term negative effects of the lockdown, supporting individuals more prone to change for the worse.     

Randomized comparison of ceftriaxone versus ceftriaxone plus amikacin for the empirical treatment of infections in patients with altered host defense: microbiological and clinical evaluation.

Two hundred and eighty-four febrile episodes in immunocompromised patients were treated with ceftriaxone alone or in combination with amikacin. In the ceftriaxone-treated group, 60 out of 143 febrile episodes were microbiologically documented, while in the group receiving the combination therapy, there were 32 out of 140 (p = 0.0007). Gram-positive microorganisms were more common than gram-negative ones, accounting for 59 of the 101 isolated bacteria. The ceftriaxone regimen appeared to have a response rate comparable to the combination regimen (73.91 vs. 78.88%). Superinfections occurred under both regimens.     

Tubby protein in human lymphocytes from normal weight and obese subjects

OBJECTIVES: The presence of tubby protein in human lymphocytes was investigated and their electrophoretic mobility property between normal weight and obese subjects was compared. DESIGN AND METHODS: 2-DE proteome map of lymphocytes has been generated and western blot analysis was conducted using anti-tub polyclonal antibody. RESULTS AND CONCLUSIONS: We found the presence of tubby protein both in normal weight and in obese subjects; however in the latter an isoelectric point shift toward the acidic end was observed.     

Automated Neuron Tracing Methods: An Updated Account

The reconstruction of neuron morphology allows to investigate how the brain works, which is one of the foremost challenges in neuroscience. This process aims at extracting the neuronal structures from microscopic imaging data. The great advances in microscopic technologies have made a huge amount of data available at the micro-, or even lower, resolution where manual inspection is time consuming, prone to error and utterly impractical. This has motivated the development of methods to automatically trace the neuronal structures, a task also known as neuron tracing. This paper surveys the latest neuron tracing methods available in the scientific literature as well as a selection of significant older papers to better place these proposals into context. They are categorized into global processing, local processing and meta-algorithm approaches. Furthermore, we point out the algorithmic components used to design each method and we report information on the datasets and the performance metrics used.