Characterization of a model of chronic orofacial hyperalgesia in the rat: contribution of NA(V) 1.8.

The purpose of this study was to develop and characterize a model of orofacial inflammatory hyperalgesia. Injection of complete Freund's adjuvant (CFA) into the upper lip/whisker pad of the rat produced significant and long-lasting thermal (> or =14 days) and mechanical (> or =28 days) hyperalgesia in the area of CFA injection. Both indomethacin and morphine, given systemically, significantly attenuated thermal hyperalgesia; the effect of morphine was shown to be opioid receptor-mediated. We also examined the contribution of the tetrodotoxin-resistant voltage-gated sodium channel Na(v)1.8 in CFA-produced orofacial mechanical hypersensitivity. Na(v)1.8 mRNA was increased > or =2.5-fold in trigeminal ganglion neurons 1 and 2 weeks after CFA treatment, and Na(v)1.8 protein was increased in the infraorbital nerve over a similar time course. The changes observed were time-dependent and had returned to baseline when examined 2 months after inflammation; there were no changes in Na(v)1.9 mRNA in trigeminal ganglion neurons after CFA treatment. In support of this, Na(v)1.8 antisense oligodeoxynucleotide treatment significantly attenuated CFA-produced mechanical hypersensitivity. These results document development of a model of inflammatory orofacial hyperalgesia, which, consistent with other reports, indicate a contribution of tetrodotoxin-resistant, voltage-gated sodium channel Na(v)1.8. PERSPECTIVE: Orofacial hypersensitivity develops postoperatively as a routine course of orofacial surgery, and mechanical allodynia is characteristic of temporomandibular joint disorder. The results described in this report are novel with respect to the duration of orofacial hypersensitivity produced and suggest that pharmacological targeting of the voltage-gated sodium channel Na(v)1.8 may be useful in managing hypersensitivity.     

Disseminated syringomas of the upper extremities. Case history and immunohistochemical and ultrastructural study.

A case of disseminated syringomas with unusual distribution and high age of onset is reported. The 66-year-old male patient presented with multiple lesions confined to dorsum of both hands and flexor side of both forearms. Morphological and immunohistochemical studies using keratin, S-100, carcinoembryonic antigen, and epithelial membrane antigen antibodies were performed both at light microscopical and ultrastructural level. These investigations revealed the presence of keratin filament containing colloid bodies near syringomatous epithelia. Reactivity for carcinoembryonic antigen could be demonstrated on the membranes of intracytoplasmic vesicles as well as within luminal debris. Absence of S-100 and epithelial membrane antigen in the tumor and ultrastructural features indicate ductal origin of syringoma.     

Kleine Granula in den Epithelzellen der menschlichen Hornhaut

Zusammenfassung Die elektronenmikroskopische Untersuchung von in Osmium-Zink-Jodid-(OZJ) fixierten menschlichen Hornhautepithelien erbrachte den Nachweis zahlreicher OZJ-positiver intracytoplasmatischer Körperchen in den basalen Zellschichten. Die entsprechenden Äquivalente dieser Granula konnten auch in routinemäßig mit Glutaraldehyd-Osmiumtetroxyd fixierten Hornhautepithelien gefunden werden. Sie sind etwa 1000–2000 Å groß, rund bis oval, haben eine deutliche, begrenzende Membran (unit membrane) und einen elektronendichten, feingranulären Inhalt. Dieser Inhalt wird durch Osmium-Zink-Jodid geschwärzt, wenn die Körperchen keinen Kontakt mehr zum Extracellularraum haben. Sie liegen vorwiegend in der Peripherie der Zellen. Obwohl die Größe, die Konfiguration, die Lokalisation in der Zellperipherie und das Verhalten gegenüber dem OZJ mit den als Keratinosomen bekannten Organellen verschiedener anderer — meist verhornender — Epithelien übereinstimmt, erlaubt das Auftreten in den basalen Zellschichten und das Fehlen einer lamellären Innenstruktur doch eine deutliche Unterscheidung der beschriebenen Granula von Keratinosomen.Auf Grund ihrer Ultrastruktur werden diese OZJ-positiven Granula der Hornhaut als Manifestationen der Encytose aufgefaßt.

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Small granules in epithelial cells of human cornea

Summary Ultrastructural investigations of human corneal epithelium fixed in osmium-zinc-iodide (OZJ) proved the presence of a large number of OZJ-positive intracytoplasmic granules in the basal cell layers. The respective equivalents of these granules could also be found in corneal epithelium fixed in glutaraldehydosmiumtetroxyde. They are of approximately 1000–2000 Å size, round to ovoid shape, possess a clearly defined unit membrane, and an electron-dense fine grained internal structure which is heavily stained by OZJ when the granules loose contact with the extracellular space. These granules are found mainly in the periphery of the cytoplasm. Although in size, configuration, and position at the periphery of cells and their reaction to OZJ, the granules correspond to organelles known as keratinosomes of various other — mostly keratinizing — epithelia, their presence in basal cell layers and the absence of a lamellar internal structure allow a clear differentiation between these granules and keratinosomes.On the basis of their ultrastructure, OZJ-positive granules of the cornea are conceived as manifestations of encytosis.

     

Different types of benign nerve sheath tumors

Summary In a light-, electronmicroscopic and autoradiographic study different types of nerve sheath tumors were classified. Their cellular population was quantitatively evaluated in the electron microscope.In the neurinoma the predominant cell was found to be the Schwann cell, but in the different types of neurofibromata a variable content of connective tissue cells was noted. The diffuse neurofibromata showed a quantitative cellular composition similar to normal peripheral nerves. In the plexiform neurofibroma a large number of fibroblasts were present and in the argyrophilic neurofibroma high content of perineurial cells was found. In autoradiographic sections the tumors showed in general a low proliferation rate (L.i. 1–3.6%). In the argyrophilic neurofibrom a higher labelling index (9.5%) was found.

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Zusammenfassung Verschiedene Typen von Nervenscheidentumoren wurden lichtmikroskopisch, elektronenmikroskopisch und autoradiographisch untersucht. Die elektronenmikroskopische quantitative Bestimmung der verschiedenen Zelltypen in den Tumoren ergab bei den Neurinomen eine überwiegende Beteiligung von Schwannschen Zellen (87,1%). Bei den Neurofibromen konnte eine unterschiedlich gro\e Anzahl von Bindegewebszellen nachgewiesen werden. Die diffusen Neurofibrome wiesen im allgemeinen eine Zellpopulation auf, wie man sie auch in normalen peripheren Nerven finden kann. Bei den plexiformen Neurofibromen überwogen die Fibroblasten und bei den argyrophilen Neurofibromen wurde eine hohe Perineuralzellbeteiligung gefunden. Die Proliferationsrate der Tumore in der Autoradiographie war im allgemeinen relativ gering, nur das argyrophile Neurofibrom wies einen deutlich höheren Markierungsindex (9,5%) auf.

     

Factor X deficiency in the neonatal period

An infant with a severe deficiency of factor X presened in the neonatal period with uncontrollable bleeding from heel prick sites, spontaneous bruising, and haematoma. The deficiency was controlled by infusions of dried human factors II, IX, and X concentrate; the half-life of the infused factor X material is only 18 hours. Despite prophylactic weekly infusions of factor X concentrate, the child developed a fatal intracerebral haemorrhage when only 4 months old. Coagulation studies on both parents and the elder sister showed no obvious coagulation abnormality.     

Effects of focal electrical stimulation and morphine microinjection in the periaqueductal gray of the rat mesencephalon on neuronal activity in the medullary reticular formation

Neurons in the medullary reticular formation (MRF; nucleus reticularis gigantocellularis and nucleus reticularis paragigantocellularis) were evaluated for their involvement in the analgesia produced by focal electrical stimulation and microinjection of morphine into the periaqueductal gray region (PAG) of the rat mesencephalon. Analgesia-producing PAG stimulation altered the spontaneous activity of 80% of the neurons in the MRF (both excitation and inhibition were observed) and inhibited the noxious-evoked excitation of 75% of MRF neurons. Microinjection of morphine into the PAG also increased (50%) and decreased (17%) the spontaneous activity of MRF units and inhibited the noxious-evoked excitation of 47% of MRF neurons. These effects were specific for analgesia produced by the PAG manipulations and were partially reversed by naloxone. The role of the MRF in PAG-induced analgesias and the degree of overlap in neuronal systems influenced by intracranial morphine and electrical stimulation is discussed.