Physicochemical aspects of drug release. XV. Investigation of diffusional transport in dissolution of suspended, sparingly soluble drugs

The dissolution rates of sparingly soluble, fine particulate, suspended drugs have been studied using a Coulter Counter Model TAII. For two sieve fractions of oxazepam the dissolution rates were monitored in media with varying viscosities brought about by the addition of glycerol, while for griseofulvin the change in the medium's viscosity was induced by changing the temperature. By calculating the dissolution rate, and compensating for differences in particle surface area and media solubility, it was shown that the dissolution rate was diffusion controlled. After additional normalization for the diffusion coefficient, it was suggested that the so-called apparent diffusional distance decreased substantially with particle size. The effect of particle size was more limited above approx. 15 μm.     

The use of the rat facial nerve model to assess the effect of differing nerve anastomotic agents on the facial nerve

There are relatively few papers which prove that one nerve anastomotic agent for the facial nerve is superior to any other. Previous experiments on the division and anastomosis of the facial nerve have failed to consider the indeterminate variables involved, i.e. operator variability, controls and the reaction of the materials on normal nerve tissue. In this experiment, a variety of anastomotic agents were tested to see if the anastomotic agents themselves affected the extra-temporal facial nerve function. The absorbable suture, non-absorbable suture, glue and tube wrap used had no effect on normal nerve tissue or on the anastomosis of the sectioned facial nerve of the rat compared with simple laying together of the divided ends of the divided nerve.     

Vagus Nerve Stimulation Induces a Sustained Anticonvulsant Effect

Summary: Purpose: Stimulation of the vagus nerve can effectively abort several types of experimentally induced seizures in animals when administered near the time of seizure onset. Indirect evidence from human trials and animal studies suggests that the anticonvulsant effects of vagus nerve stimulation (VNS) extend beyond the duration of stimulation. We used the pentylenetetrazol model to determine whether VNS exerts a persistent anticonvulsant effect.
Methods: VNS (1 mA, 30 Hz, 500 μs pulse width) was administered continuously for 0, 1, or 60 min, or intermittently (30 s on, 5 min off) for 60 min, to awake and freely moving animals. After the end of stimulation, pentylenetetrazol (50 mg/kg i.p.) was administered to induce seizures. Time-course studies were also performed, consisting of 60 min of VNS followed by pentylenetetrazol injection after 0, 3-, 5-, and 10-min intervals.
Results: The greatest anticonvulsant effect occurred after 60 min of continuous VNS, which prevented convulsions in four of 12 rats and reduced significantly seizure duration, the total number of seizures, and number of tonic seizures. Intermittent VNS was less effective than continuous stimulation for 60 min, but more effective than that for 1 min. The anticonvulsant effect declined in a time-dependent fashion after discontinuation of VNS, with return to nonstimulated control values by 10 min.
Conclusions: The results of this study verify a persistent VNS-induced anticonvulsant effect and indicate that its efficacy is dependent on the cumulative stimulus duration.     

实验冻伤大鼠神经纤维的超微结构改变

为探讨冷冻损伤发生、发展及转归的规律，采用健康Ｗｉｓｔａｒ大鼠，分为冻伤组（２０只）和对照组（５只）。电镜下观察大鼠后肢冷冻至－２０℃后即刻、４小时、２４小时及７２小时时周围神经的超微结构改变。冻后即刻，神经髓鞘即出现轻度变性；冻后１～２４小时，有髓神经雪旺细胞及轴突严重变性，而无髓神经变性较轻；冻后７２小时，神经溃变及修复并存，无髓神经较有髓神经易于修复。     

Visual system of a naturally microphthalmic mammal: The blind mole rat,Spalax ehrenbergi

Retinal projections and visual thalamo-cortical connections were studied in the subterranean mole rat, belonging to the superspecies Spalax ehrenbergi, by anterograde and retrograde tracing techniques. Quantitative image analysis was used to estimate the relative density and distribution of retinal input to different primary visual nuclei. The visual system of Spalax presents a mosaic of both regressive and progressive morphological features. Following intraocular injections of horseradish peroxidase conjugates, the retina was found to project bilaterally to all visual structures described as receiving retinal afferents in non-fossorial rodents. Structures involved in form analysis and visually guided behaviors are reduced in size by more than 90%, receive a sparse retinal innervation, and are cytoarchitecturally poorly differentiated. The dorsal lateral geniculate nucleus, as defined by cyto- and myelo-architecture, cytochrome oxidase, and acetylcholinesterase distribution as well as by afferent and efferent connections, consists of a narrow sheet 3–5 neurons thick, in the dorsal thalamus. Connections with visual cortex are topographically organized but multiple cortical injections result in widespread and overlapping distributions of geniculate neurons, thus indicating that the cortical map of visual space is imprecise. The superficial layers of the superior colliculus are collapsed to a single layer, and the diffuse ipsilateral distribution of retinal afferents also suggests a lack of precise retinotopic relations. In the pretectum, both the olivary pretectal nucleus and the nucleus of the optic tract could be identified as receiving ipsilateral and contralateral retinal projections. The ventral lateral geniculate nucleus is also bilaterally innervated, but distinct subdivisions of this nucleus or the intergeniculate leaflet could not be distinguished. The retina sends a sparse projection to the dorsal and lateral terminal nuclei of the accessory optic system. The medial terminal nucleus is not present. In contrast to the above, structures of the “non-image forming” visual pathway involved in photoperiodic perception are well developed in Spalax. The suprachiasmatic nucleus receives a bilateral projection from the retina and the absolute size, cytoarchitecture, density, and distribution of retinal afferents in Spalax are comparable with those of other rodents. A relatively hypertrophied retinal projection is observed in the bed nucleus of the stria terminalis. Other regions which receive sparse visual input include the lateral and anterior hypothalamic areas, the retrochiasmatic region, the sub-paraventricular zone, the paraventricular hypothalamic nucleus, the anteroventral and anterodorsal nuclei, the lateral habenula, the mediodorsal nucleus, and the basal telencephalon. These results indicate that the apparently global morphological regression of the visual system conceals a selective expansion of structures related to functions of photoperiodic perception and photo-neuroendocrine regulation. We suggest that the evolution of an atrophied eye and reduced visual system is an adaptively advantageous response to the unique subterranean environment. Factors favoring regression include mechanical aspects, metabolic constraints, and competition between sensory systems. The primary advantage of sensory atrophy is the metabolic economy gained by the reduction of visual structures which do not contribute significantly to the animal's fitness. © 1993 Wiley-Liss, Inc.     

Effects of Vagal and Sympathetic Nerves on Transmembrane Potential of Cardiac Ventricular Cells of Toad

The effects of vagal and sympathetic nerves on the transmembranepotentials of cardiac cells of toad were observed by means of microelectrodetechnique.The vagal nerve was stimulated there would be an increase in restingpotential and acceleration in repolarization of action potential(AP).However,ifatropine was used before stimulation the above-mentioned phenomena woulddisappear.When the sympathetic nerve was stimulated the AP amplitudeincreased,but resting potential(RP)remained the same.The increase of APresulted from the increases of overshoot.When the sympathetic nerve wasstimulated although the heart rate increased and the duration of AP wasshortened,the plateau phase of AP was prolonged.These results suggest that theeffects of vagal and sympathetic nerves on the transmembrane potential of cardiacventricular cells are coordinated and the normal characteritics of transmembranepotential are maintained by both the vagal and sympathetic nerves.     

Effect of electric and chemical stimulation of the raphe obscurus on phrenic nerve activity in the cat

The effect of electrical and chemical (l-glutamate) stimulation of the raphe obscurus on phrenic nerve activity was examined in the cat. Phrenic nerve activity was recorded from a C5 nerve root in anesthetized, paralyzed and artificially ventilated cats. Neural discharge was quantitated by integrating the phrenic nerve activity. The respiratory frequency was determined from the integrated nerve signal. Focal electrical stimulation (18–144 μA; 5–40 Hz; 100 μs pulse duration) resulted in significant (P < 0.05) increases in both integrated phrenic nerve (IPN) amplitude and respiratory frequency. These changes were dependent upon current intensity and frequency of stimulation. The largest increases in IPN amplitude and respiratory frequency were47 ± 17%and146 ± 8%, respectively. To insure that the changes in integrated phrenic nerve activity (IPNA) were the result of stimulation of cell bodies and not axons of passage,l-glutamate (100, 200 nmol) was microinjected (100 nl) into the raphe obscurus. Significant (P < 0.05) dose-related changes occurred in integrated phrenic nerve amplitude with an increase of44 ± 13% at 100 nmol and80 ± 13% at 200 nmoll-glutamate. No significant increase in respiratory frequency was observed withl-glutamate microinjection. The results suggest that the raphe obscurus may be involved in respiratory control.     

Tenotomy prevents the functional improvement of a muscle reinnervated with a chronically severed nerve

During the early stages of nerve implantation, we followed the dynamic properties of the lateral gastrocnemius muscle of the rat, reinnervated with an acutely or chronically severed peroneal nerve. The aim of this study was to ascertain whether (1) the better functional recovery of a muscle reinnervated by a chronically severed foreign nerve is present from the onset of reinnervation, and (2) whether such functional improvement is due to the conditioning lesion effect. Our results indicate that better functional recovery is already apparent one week after nerve implantation, and it is due to the conditioning lesion effect, since tenotomy prevents such improvement. The tenotomy effect underlines the fact that some environmental factors concerning the target tissue, and not only the predegenerated nerve, are involved in the conditioning effect. © 1995 Wiley-Liss, Inc.