Naloxone and nalmefene absorption delivered by hollow microneedles compared to intramuscular injection

Naloxone and nalmefene were administered to seven research Beagle dogs, (mean weight approximately 12 kg) at a dose of 0.04 mg/kg and 0.014 mg/kg for naloxone and nalmefene, respectively. Each dose was administered intramuscularly (IM) with a standard IM injection and with a hollow microneedle device array using needles of 1 mm in length. The IM injection was delivered in the epaxial muscles, and the microneedle injection was delivered in the skin over the shoulder of each dog. Each dog received the same injections in a cross-over design. Following the injection, blood samples were collected for plasma analysis of naloxone and nalmefene by high pressure liquid chromatography with mass spectrometry detection (LCMS). The plasma sample concentrations were plotted for observed patterns of absorption and analyzed with non-compartmental pharmacokinetic methods (NCA). The results showed that the injection of naloxone from the microneedle device produced a higher peak concentration (CMAX) by 2.15x compared the IM injection of the same dose, and time to peak concentration (TMAX) was similar. For the nalmefene injection, the peak was not as high (lower CMAX) by 0.94x for the microneedle injection compared to the IM injection of the same dose. The microneedle produced an exposure, measured by area under the curve (AUC)) that was 0.85x and 0.58x as high for naloxone and nalmefene, respectively, than the injection by the IM route. We also observed that although the dose for naloxone was approximately 3x higher for naloxone compared to nalmefene, the mean peak concentration achieved from the naloxone injection was more than 12x higher than the nalmefene injection. These studies were designed to test the feasibility of using the hollow microneedle array as an effective method of naloxone and nalmefene delivery for emergency treatment of opioid-induced respiratory depression (OIRD). The results of these studies will form the basis of future studies, using the dog as a model, for development of hollow microneedle microarray devices to deliver opioid antagonists for treatment of OIRD in people.

Zic1 advances epaxial myotome morphogenesis to cover the neural tube via Wnt11r

The dorsal axial muscles, or epaxial muscles, are a fundamental structure covering the spinal cord and vertebrae, as well as mobilizing the vertebrate trunk. To date, mechanisms underlying the morphogenetic process shaping the epaxial myotome are largely unknown. To address this, we used the medaka zic1/zic4-enhancer mutant Double anal fin (Da), which exhibits ventralized dorsal trunk structures resulting in impaired epaxial myotome morphology and incomplete coverage over the neural tube. In wild type, dorsal dermomyotome (DM) cells, progenitors of myotomal cells, reduce their proliferative activity after somitogenesis and subsequently form unique large protrusions extending dorsally, potentially guiding the epaxial myotome dorsally. In Da, by contrast, DM cells maintain the high proliferative activity and form mainly small protrusions. By combining RNA- and ChIP-sequencing analyses, we revealed direct targets of Zic1 which are specifically expressed in dorsal somites and involved in various aspects of development, such as cell migration, extracellular matrix organization and cell-cell communication. Among these, we identified wnt11r as a crucial factor regulating both cell proliferation and protrusive activity of DM cells. We propose that the dorsal movement of the epaxial myotome is guided by DM cells and that Zic1 empowers this activity via Wnt11r to achieve the neural tube coverage.

Multifactorial Causes of Chronic Mortality in Juvenile Sturgeon (Huso huso)

This investigation focused on an episode of chronic mortality observed in juvenile Huso huso sturgeons. The examined subjects underwent pathological, microbiological, molecular, and chemical investigations. Grossly severe body shape deformities, epaxial muscle softening, and multifocal ulcerative dermatitis were the main observed findings. The more constant histopathologic findings were moderate to severe rarefaction and disorganization of the lymphohematopoietic lymphoid tissues, myofiber degeneration, atrophy and interstitial edema of skeletal epaxial muscles, and degeneration and atrophy of the gangliar neurons close to the myofibers. Chemical investigations showed a lower selenium concentration in affected animals, suggesting nutritional myopathy. Other manifestations were nephrocalcinosis and splenic vessel wall hyalinosis. Septicemia due to bacteria such as Aeromonas veronii, Shewanella putrefaciens, Citrobacter freundii, Chryseobacterium sp., and pigmented hyphae were found. No major sturgeon viral pathogens were detected by classical methods. Next-generation sequencing (NGS) analysis confirmed the absence of viral pathogens, with the exception of herpesvirus, at the order level; also, the presence of Aeromonas veronii and Shewanella putrefaciens was confirmed at the family level by the metagenomic classification of NGS data. In the absence of a primary yet undetected biological cause, it is supposed that environmental stressors, including nutritional imbalances, may have led to immune system impairment, facilitating the entry of opportunistic bacteria and mycotic hyphae.

Fishes can use axial muscles as anchors or motors for powerful suction feeding

ABSTRACTSome fishes rely on large regions of the dorsal (epaxial) and ventral (hypaxial) body muscles to power suction feeding. Epaxial and hypaxial muscles are known to act as motors, powering rapid mouth expansion by shortening to elevate the neurocranium and retract the pectoral girdle, respectively. However, some species, like catfishes, use little cranial elevation. Are these fishes instead using the epaxial muscles to forcefully anchor the head, and if so, are they limited to lower-power strikes? We used X-ray imaging to measure epaxial and hypaxial length dynamics (fluoromicrometry) and associated skeletal motions (XROMM) during 24 suction feeding strikes from three channel catfish (Ictalurus punctatus). We also estimated the power required for suction feeding from oral pressure and dynamic endocast volume measurements. Cranial elevation relative to the body was small (<5 deg) and the epaxial muscles did not shorten during peak expansion power. In contrast, the hypaxial muscles consistently shortened by 4–8% to rotate the pectoral girdle 6–11 deg relative to the body. Despite only the hypaxial muscles generating power, catfish strikes were similar in power to those of other species, such as largemouth bass (Micropterus salmoides), that use epaxial and hypaxial muscles to power mouth expansion. These results show that the epaxial muscles are not used as motors in catfish, but suggest they position and stabilize the cranium while the hypaxial muscles power mouth expansion ventrally. Thus, axial muscles can serve fundamentally different mechanical roles in generating and controlling cranial motion during suction feeding in fishes.

Sensorial, Physico-chemical and Nutritive Characterization of Paddlefish (Polyodon spathula) Meat

In the current paper were studied a number of 200 sturgeons from Polyodon spathula of 4th summer (P.s.3+) breed, reared in a fishery farm from North-East of Romania. Studying of modification of sensorial characteristics of meat, analysed just after fishing and during preservation by refrigeration during 15 days (+2 � +4oC), show an optimal keeping period by refrigeration of the studied fishes for 5-6 days. The pH level from the studied muscles oscillated between values 7.9 and 7.11, after slaughtering, and at 24 h after slaughtering between 6.88 and 6.89. The water content of fillet (lateral muscles) had values of 75.41%; protein content of fillet (lateral muscles) had values of 19.89%; lipid content of fillet (lateral muscles) was 3.45%; collagen content of fillet (lateral muscles) had values of 4.14%. The values of water-protein rate (w/p = 3.79) placed the analyzed paddlefishes in the second category; energetic value of fillet gathered from studied fishes was 114.31 kcal/100 g. The rate of amino-acids from the total sum was 26.23% for the essential amino acids, 4.61% for semi-essential amino acids and 69.16% for non-essential amino acids. As rate the quantity of saturated fatty acids recorded the value of 25.64% for epaxial muscles, respectively 25.83% for hypaxial muscles; rate of mono-unsaturated fatty acids was 54.77% for epaxial muscles and 54.50% for hypaxial muscles; poly-unsaturated fatty acids had a rate of 19.59% for epaxial muscles and 19.67% for hypaxial muscles. Through histological studies for establishing the rate of muscular and conjunctive tissues from meat of studied paddlefishes, was observed that in case of lateral muscles mean diameter had an intermediary value of 43.42 �. Those data leaded to obtain a mean area for transversal section of 1485.74 �2. Mean diameter of muscular fibre (43.42 �) characterize a meat with fine texture. Profile on transversal section of muscular fibres had an ellipsoidal shape; fact which was enlightened by the rate between great diameter and small diameter (GD/SD) which varied between 1.35/1 -1.61/1. The rate of the main tissue categories in composition of lateral muscles gathered from analysed paddlefishes revealed the fact that mean rate of muscular tissue was of 70.47%, while mean rate of conjunctive tissues was of only 29.52%.

Cross-sectional area and fat content in dachshund epaxial muscles: an MRI and CT reliability study

MRI and CT are frequently used to diagnose spinal diseases in dogs. These modalities have detected epaxial muscle degeneration in dachshunds with intervertebral disc herniation. However, research on the reliability of epaxial muscular measurements is limited in veterinary medicine. The aims of the study were to assess the intrarater and inter-rater reliability of epaxial muscle cross-sectional area (CSA) and fat content measurements on MRI and CT images in dachshunds, and to compare the CSA measurement between the two modalities. MRI and CT images of 10 healthy dachshunds were evaluated. Two blinded observers assessed MRI CSA, MRI fat content, CT CSA and CT muscle attenuation of three thoracolumbar epaxial muscles using OsiriX. The results showed ‘substantial’ to ‘almost perfect’ intrarater reliability (intraclass correlation coefficient (ICC) 0.828–0.998) and inter-rater reliability (ICC 0.685–0.854) for all variables. When individual spinal segments were analysed, the intrarater and inter-rater reliability decreased and the confidence intervals increased. There was positive correlation (r= 0.719–0.841, P=0.001) and high agreement (0.824–0.894) for the measured CSA between MRI and CT. Epaxial muscle CSA and fat content can be reliably measured on MRI and CT, bearing in mind that measurement of certain segments requires adequate training.