The n-acetyl phenylalanine glucosamine derivative attenuates the inflammatory/catabolic environment in a chondrocyte-synoviocyte co-culture system

Osteoarthritis (OA), the most prevalent degenerative joint disease, still lacks a true disease-modifying therapy. The involvement of the NF-κB pathway and its upstream activating kinases in OA pathogenesis has been recognized for many years. The ability of the N-acetyl phenylalanine glucosamine derivative (NAPA) to increase anabolism and reduce catabolism via inhibition of IKKα kinase has been previously observed in vitro and in vivo. The present study aims to confirm the chondroprotective effects of NAPA in an in vitro model of joint OA established with primary cells, respecting both the crosstalk between chondrocytes and synoviocytes and their phenotypes. This model satisfactorily reproduces some features of the previously investigated DMM model, such as the prominent induction of ADAMTS-5 upon inflammatory stimulation. Both gene and protein expression analysis indicated the ability of NAPA to counteract key cartilage catabolic enzymes (ADAMTS-5) and effectors (MCP-1). Molecular analysis showed the ability of NAPA to reduce IKKα nuclear translocation and H3Ser10 phosphorylation, thus inhibiting IKKα transactivation of NF-κB signalling, a pivotal step in the NF-κB-dependent gene expression of some of its targets. In conclusion, our data confirm that NAPA could truly act as a disease-modifying drug in OA

Urinalysis in Great Dane Puppies from Birth to 28 Days of Age

Urinalysis, a common test in infants, could represent a suitable non-invasive clinical tool in puppies. In dog neonates, urine is easily collected by stimulating the somato-vesccal reflex. Information on urine characteristics during the neonatal period is missing. Beside instrumental laboratory analyses, the dipstick was proven useful for rapid urinalysis to evaluate specific gravity (SG), pH, leukocytes, nitrites, glucose, proteins, ketones, urobilinogen, bilirubin, and blood. The present study aimed to describe urinalysis features by the dipstick test and refractometer along the neonatal period. Urine samples (n = 624) were collected by manual stimulation from 48 healthy Great Danes, daily from birth to seven days, then twice a week until 28 days, to assess age-related changes (ANOVA, p < 0.05) and the possible effects of gender and litter (T-test, p < 0.05). The SG and pH significantly changed during the neonatal period. Other parameters did not vary significantly in relation to age. No significant differences were observed either among litters or between genders. The present study confirmed that canine kidneys are able to concentrate urine from the second week of age when the urinary SG started to be similar to adults, while pH still increased towards the typical values of adults at 28 days. Significant glucosuria and proteinuria were never detected. Dipstick urinalysis represents a useful first-line complementary tool in newborns clinical examination, providing information about systemic homeostasis

Apgar score or birthweight in Chihuahua dogs born by elective Caesarean section : which is the best predictor of the survival at 24 h after birth?

In the dog, the correct management of parturition and the prompt neonatal evaluation and assistance can reduce the perinatal mortality rates that are particularly high in toy breeds. Newborn evaluation and factors addressing prognosis are pivotal to guarantee the correct neonatal assistance. Assessment of the Apgar score with viability classification and birthweight are recognized as predictors for neonatal survival in dogs, but breed-specific data are needed for a more feasible application in the dog species, in which wide differences among breeds are known. The present study aimed therefore to: (a) assess the role of Apgar score and birthweight as predictors for the survival of Chihuahua newborn puppies in the first 24 h of life; (b) to assess a cut-off of the Apgar score and birthweight values that can predict the survival of Chihuahua newborn puppies in the first 24 h after birth; (c) to assess the possible effect played by maternal parity, newborn gender and litter-size on Apgar score in Chihuahua newborn puppies, in order to provide breed-specific data for a better neonatal assistance..Data obtained from 176 normal developed Chihuahua puppies born by elective Caesarean section, showed that 62%, 28% and 10% of puppies were classified in the Apgar score classes 7\u201310, 4\u20136 and 0\u20133, respectively, with survival at 24 h after birth of 97%, 96%, 39%, in the three Apgar classes of viability, respectively. Apgar score was a better predictor for survival at 24 h after birth than birthweight (AUC 0.93, P < 0.0001; AUC 0.69, P < 0.01, respectively). Litter-size of 7 puppies/litter plays a negative effect on Apgar score. Apgar score is a better predictor of survival at 24 h than birthweight, and the best cut-off of Apgar score for survival at 24 h after birth is 4, with 96% sensitivity and 77% specificity. The different proportion of \u201cnormal viable\u201d and \u201cless viable\u201d neonates in comparison to other studies highlights that Chihuahua puppies born by elective Caesarean section should be carefully evaluated at birth to provide correct assistance

Clinical efficacy of medical hydrology: an umbrella review

The aim of this research was to summarize available scientific evidence on the efficacy of medical hydrology for the management of any health condition. The search was conducted on 26th March 2021, in the following databases: Medline (via PubMed), EMBASE, Web of Science, Cochrane Library, and Google Scholar. All relevant literature reviews investigating the clinical efficacy of interventions characterized by the use of natural mineral waters and muds were included. The quality of studies was assessed with the “AMSTAR 2” tool. After article screening, 49 reviews were included in this work. Overall, retrieved scientific evidence suggests that spa therapy is beneficial for patients affected by some specific musculoskeletal conditions, with improvements potentially lasting up to 9 months. Moreover, balneotherapy can be an integrative support for the management of chronic venous insufficiency and some inflammatory skin diseases like psoriasis. The role of spa therapy in rehabilitation appears relevant as well. More limited, although interesting evidence exists for inhalation and hydropinic therapies. Globally, retrieved evidence suggests that, besides individual wellbeing, medical hydrology can be useful for public health. In particular, higher-quality studies seem to support the integrative use of spa-related interventions for conditions like osteoarthritis, fibromyalgia, low back pain of rheumatic origin, and chronic venous insufficiency. However, the body of evidence has some limitations and further clinical trials should be designed for each relevant application to consolidate and expand acquired knowledge

DOPAL derived alpha-synuclein oligomers impair synaptic vesicles physiological function

Parkinson's disease is a neurodegenerative disorder characterized by the death of dopaminergic neurons and by accumulation of alpha-synuclein (aS) aggregates in the surviving neurons. The dopamine catabolite 3,4-dihydroxyphenylacetaldehyde (DOPAL) is a highly reactive and toxic molecule that leads to aS oligomerization by covalent modifications to lysine residues. Here we show that DOPAL-induced aS oligomer formation in neurons is associated with damage of synaptic vesicles, and with alterations in the synaptic vesicles pools. To investigate the molecular mechanism that leads to synaptic impairment, we first aimed to characterize the biochemical and biophysical properties of the aS-DOPAL oligomers; heterogeneous ensembles of macromolecules able to permeabilise cholesterol-containing lipid membranes. aS-DOPAL oligomers can induce dopamine leak in an in vitro model of synaptic vesicles and in cellular models. The dopamine released, after conversion to DOPAL in the cytoplasm, could trigger a noxious cycle that further fuels the formation of aS-DOPAL oligomers, inducing neurodegeneration

How stressful is maternity? Study about cortisol and dehydroepiandrosterone-sulfate coat and claws concentrations in female dogs from mating to 60 days post-partum

In dogs, the phase from mating to the end of weaning lasts about 120 days and encompasses many aspects that, interacting, contribute to increase the allostatic load. The coat and claws, useful for long-term change assessments, have the advantage of being collectable without invasiveness. In the present study, the Cortisol (C) and Dehydroepiandrosterone-sulfate (DHEA-S) concentration monthly changes in the coat and claws were studied in female dogs from mating to the end of weaning to assess Hypothalamic\u2013Pituitary\u2013Adrenal (HPA) axis activation during pregnancy and the post-partum period. The results from 15 Dobermann Pinscher female dogs showed a trend of increase of the coat C from mating to 60 days post-partum, with significant changes between mating and parturition-60 days post-partum (p < 0.01) and between the 30-day pregnancy diagnosis (PD) and 30\u201360 days post-partum (p < 0.05). The claws C trend showed significant increases between mating and 30\u201360 days post-partum (p < 0.05) and between the PD and 60 days post-partum (p < 0.01). DHEA-S in both matrices showed non-significant changes. The results suggest that maternity could play a pivotal role in the HPA axis activation, with a subsequent chronic secretion of C determining an increase in the allostatic load in the mothers. Neither maternal parity nor litter size played a significant role in the accumulation of C and DHEA-S in both matrices

Pulsed Current Effect on the Hard Anodizing of an AlSi10Mg Aluminum Alloy Obtained via Additive Manufacturing

The hard anodizing treatments of cast Al-Si alloys are notoriously difficult. Indeed, their microstructural features hinder the growth of a uniform, compact, and defect-free anodic oxide. In this paper, AlSi10Mg samples, produced via Gravity Casting (GC) and Additive Manufacturing, i.e., Laser Powder Bed Fusion (L-PBF), were hard anodized in a sulfuric acid bath, in order to verify how the particular microstructure obtained via L-PBF affects the thickness, hardness, compactness, and defectiveness of the anodic oxide. Moreover, for the first time, Pulsed Direct Current (PDC) procedures were used to perform the hard anodizing treatments on additively manufactured AlSi10Mg alloy. Several combinations of temperature and electrical parameters, i.e., current density, frequency, and Duty Cycle, were tested. The anodized samples were characterized through optical microscopy analysis, Scanning Electron Microscopy (SEM) analysis, and accelerated corrosion tests, i.e., Potentiodynamic Polarization (POL) and Electrochemical Impedance Spectroscopy (EIS) measurements. The PDC procedures allowed improvement of the compromise between evenness, compactness, and defectiveness. Among the attempted PDC procedures, a specific combination of electrical parameters and temperature allowed the best results to be obtained, i.e., the highest hardness and the lowest volumetric expansion values without compromising the oxide quality rating and the corrosion resistance behavior. However, none of the attempted PCD strategies allowed the hardness values obtained on samples produced via GC to be reached

Assessment of neonatal viability : the Apgar score

In dogs, perinatal mortality is relatively high, and deaths peak around birth and during the first week of age. Among the several causes, the long process of whelping plays an important role in canine perinatal mortality. Therefore, also in dogs the early neonatal assistance to puppies is mandatory. However, in comparison to humans, knowledge and technological ability in dog neonatology are tremendously scarce. The Apgar score for the newborn viability assessment at birth represent a feasible method for the prompt recognition of newborns that needs special assistance immediately after birth. The five parameters Apgar score, adapted to the canine specie by different studies, advantages and limits, as well as clinical application are presented and discussed

Effects of Alfaxalone or Propofol on Giant-Breed Dog Neonates Viability During Elective Caesarean Sections

Nowadays, thanks to the increased awareness of owners and breeders and to the most recent techniques available to veterinarians, the management of parturition, especially of C-sections, has become a topic of greater importance. Anesthesia is crucial and must be targeted to both the mother and neonates. The present study aimed to evaluate the effect of the induction agent alfaxalone on the vitality of puppies born from elective C-section, in comparison to propofol. After inducing general anesthesia for elective C-section, puppies from the mothers induced with alfaxalone had higher 5-min Apgar scores than those induced with propofol. The concentration of cortisol in fetal fluids collected at birth is neither influenced by the anesthetic protocol used, nor does it differ between amniotic and allantoic fluids. Nevertheless, the cortisol concentration in fetal fluids affects the relationship between anesthesia and the Apgar score: the present study highlights a significant relationship between the anesthetic protocol used and Apgar score in puppies, and fetal fluids cortisol concentration acts as a covariate of this relationship. Alfaxalone is a safe and effective drug for the induction of anesthesia in dogs, and it can be successfully employed for elective C-section, with neonatal wellbeing improvements