Expression of connexin 32 gap junction protein in the kidneys during fetal development of the hamster (Mesocricetus auratus)

The expression of gap junction protein was examined immunohistochemically using affinity-purified antibody against rat liver gap junction protein, connexin 32 (Cx32), in the kidneys of fetal (gestation days 13–16) and adult Syrian golden hamsters. Phalloidin histochemical staining, PNA- and RCA I-lectin stainings, NCAM immunostaining, and alkaline phosphatase and Na⁺-K⁺-ATPase enzyme-histochemical staining were performed in combination with Cx32 immunostaining. The kidney sections were observed with a confocal scanning laser microscope. By gestation day 13, Cx32 immunoreactivity was observed in the differentiating tubules. The Cx32 staining was localized on the lateral cell membrane of the cells lining the developing proximal tubules, while the S-shaped bodies, developing distal tubules, and collecting tubules showed no positive immunostaining. As the kidney developed, the density of Cx32 immunoreactivity increased. As the gap junction provides pathways for cell-cell communication, the development of Cx32 expression may imply that this structure plays an important role in renal tubule development. Confocal scanning laser microscopy provided a clear image of the fluorescence-labeled cell structures, free from out-of-focus blur. Using the same sections, stereoscopic images were easily reconstructed from serial optical sections, and were helpful in understanding the spatial distribution of Cx32 expression in the developing fetal proximal tubules.     

HISTOPATHOLOGICAL STUDY ON PROGRESSIVE MUSCULAR DYSTROPHY—REPORT OF A CASE WITH AUTOPSY FINDINGS—

A typical case of the D uchenne type of progressive muscular dystrophy with autopsy findings was presented. Changes in the myocardial and smooth muscle of many organs were found, and the skeletal muscles also revealed florid changes.
Histopathological examination of the skeletal muscle was made in detail through light and electron microscopic observation.     

Neuroexcitatory actions of Tamiflu and its carboxylate metabolite

Oseltamivir (Tamiflu) is now being stockpiled by several governments as a first line treatment for an anticipated outbreak of avian influenza caused by H5N1. However, abnormal behaviors and death associated with the use of Tamiflu have developed into a major issue in Japan where Tamiflu is often prescribed for seasonal influenza. Thus, it is critical to determine neuropsychiatric effects of oseltamivir and to establish methods for safe administration. Using juvenile rats and rat hippocampal slices, we investigated whether oseltamivir has adverse effects on the central nervous system. Systemic injection of oseltamivir (50 mg/kg i.p.) produced no change in behavior within 2 h. However, prior injection of oseltamivir significantly altered the duration of loss of lightning reflex following ethanol injection (3.3 g/kg, i.p.). Ethanol injection in the presence of oseltamivir also resulted in enhanced hypothermia. In the CA1 region of hippocampal slices, oseltamivir (100 μM) induced paired-pulse facilitation in population spikes without changes in excitatory postsynaptic potentials. Similarly, 3 μM oseltamivir carboxylate, the active metabolite of oseltamivir, facilitated neuronal firing, though the facilitation did not involve GABAergic disinhibition. Moreover, oseltamivir carboxylate produced further facilitation following administration of 60 mM ethanol. These findings indicate that oseltamivir has effects on the central nervous system, especially when combined with other agents.     

Suppression of in vitro growth of virulent and avirulent herpes simplex viruses by cell-mediated immune mechanisms, antibody, and interferon.

A rounding cell-forming--GC strain, which is a variant of a syncytial giant cell-forming herpes simplex virus (+GC Miyama strain), was highly attenuated for Swiss, BALB/c nu/nu, and nu/+ mice, whereas +GC was highly virulent to all the mice tested. +GC and -GC were antigenically indistinguishable from each other by cross-neutralization and cross-immunization. Immunosuppression induced by cyclophosphamide converted the nonlethal -GC infection of mice into a fatal infection. -GC replication in tissue culture was more effectively suppressed by spleen cells immunized with either +GC or -GC than was the +GC replication. -GC replication was also inhibited more effectively by antibody or the antibody-dependent cell-mediated system than was the +GC replication. -GC is highly sensitive to mouse interferon, but +GC was relatively resistant. These findings indicate that attenuation of this avirulent -GC strain may be due to a high susceptibility of its replication to humoral and cell-mediated defense factors. The probable roles of each defense factor in recovery from the infection with virulent and attenuated herpes simplex virus are also discussed.     

Presynaptic opioid kappa-receptor and regulation of the release of Met-enkephalin in the rat brainstem

Opioid kappa-agonists had much more potent inhibitory effects on the high K+-evoked Met-enkephalin release from rat brain slices than did the mu- or delta-agonists. The opioid kappa- antagonist, MR2266 enhanced the evoked release of Met-enkephalin to a greater extent than did mu- or delta-antagonists in vitro and had a potent analgesia in mice in vivo. These findings suggest that the release of Met-enkephalin may be regulated in vitro and in vivo, mainly by presynaptic kappa-receptor-mediated mechanisms.