Protective role of metallothionein in bone marrow injury caused by X-irradiation

In order to elucidate the role of metallothionein (MT) in preventing the adverse effects of X-ray irradiation, we examined the susceptibility of MT-I/II null mice to bone marrow injury caused by X-irradiation and effects of pretreatment with MT-inducing metals on X-ray injury. Eight-week-old male mice were exposed to a single bout of whole-body X-irradiation at a dose between 0.1 and 6.0 Gy. The numbers of leukocytes, reticulocytes with micronuclei (MNRET) in the blood, and polychromatic erythrocytes with micronuclei (MNPCE) in the bone marrow were determined 24 hr after X-irradiation. X-irradiation significantly decreased the total number of leukocytes in MT-I/II null mice and wild-type mice in a dose-dependent manner, but the total number of leukocytes was significantly lower in MT-I/II null mice than in wild-type mice at a low dose of irradiation, between 0.1 and 1.0 Gy. X-irradiation (0.1 and 0.5 Gy) significantly increased the appearance of MNRET and MNPCE in both strains, but the increase was greater in the MT-I/II null mice than in the wild-type mice. Additional groups of mice were pre-administered bismuth nitrate or zinc sulfate to induce MT in the bone marrow cells prior to X-irradiation; the X-ray injury was prevented by such treatments in wild-type mice only. Thus, the present results suggest that MT plays a protective role against a low dose of X-ray injury.     

Relief of Post‐Tonsillectomy Pain by Release of Lidocaine From Fibrin Glue

Objectives Pain inevitably develops after resection of the palatine tonsil (tonsillectomy). Therefore, we applied a mixture of lidocaine and fibrin glue to the tonsillar fossae immediately after tonsillectomy and evaluated its analgesic effects. Study Design A prospective randomized trial. Methods Seventy‐four consecutive patients who had undergone tonsillectomy by the same surgeon (S.K.) were allocated by the sealed envelope method into three groups. After routine tonsillectomy, the operation was terminated in group A (control group), but the bilateral tonsillar fossae were covered with 1 mL fibrin glue using CaCl₂ as solution to dissolve thrombin in group B and using 4% lidocaine chloride instead of CaCl₂ in group C. No significant difference was observed in age or sex among the three groups. Analgesic effects were evaluated in terms of the postoperative days required until the patient began to eat normally and the postoperative days on which the patient desired analgesic administration. Results The mean postoperative days until the patient began to eat normally were 4.22 in group A and 3.78 in group B, showing no significant difference, but 2.83 in group C, being significantly shorter (P <.05). The mean postoperative days on which analgesic administration was necessary were 4.56 in group A and 4.91 in group B, showing no significant difference, but 2.88 in group C, being significantly shorter (P <.05). Conclusion This method can be readily performed, requires no special treatment, and appears to have adequate pain‐relieving effects.     

Transnasal bamboo foreign body lodged in the sphenoid sinus

Transnasal sphenoid sinus foreign body is a rare condition. We report a very rare case of transnasal bamboo foreign body lodged in the sphenoid sinus without damages to the orbital wall or skull base. A 69-year-old man fell down onto a bamboo stick, which snapped after penetrating his face through the right nostril. CT demonstrated that the bamboo stick stuck into the middle meatus, penetrated the ethmoid sinus just medial to the lamina papyracea and reached to the sphenoid sinus. No abnormal findings were detected in the orbit or skull base. The foreign body was removed from the nasal cavity without any complication. The endoscope was useful for evaluating possible injuries in the orbit and skull base and confirming the absence of residual foreign bodies.     

Reversible serotoninergic neurotoxicity ofN-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mouse striatum studied by neurochemical and immunohistochemical approaches

Effects ofN-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on serotonin (5-HT) were studied in mouse striatum. The 5-HT level was significantly reduced at 1 week after MPTP, though returned at 4 weeks. The level of 5-hydroxyindoleacetic acid (5-HIAA) increased at both 1 and 4 weeks. The ratio of increase in 5-HT induced by pargyline administration was larger in MPTP-pretreated mice than in vehicle-pretreated controls at 1 week, although it was identical in both groups at 4 weeks. The 5-HT immunohistochemical study confirmed the biochemical change of 5-HT. These results suggest that MPTP functionally affects the 5-HT metabolism in mouse striatum.     

Calcitonin gene-related peptide-like immunoreactive sensory fibers form synaptic contact with sympathetic neurons in the rat celiac ganglion

The present study demonstrates synaptic contact between calcitonin gene-related peptide (CGRP)-like immunoreactive axon terminals and sympathetic neurons in the rat celiac ganglion. Our observations suggest that sensory ganglion neurons directly regulate the sympathetic activity via synapses, because CGRP immunoreactive (CGRPI) fibers in this ganglion are supplied by the sensory ganglia.     

Appearance of substance P-like immunoreactive neurons in the rat superior colliculus after neonatal eye enucleation.

The possibility that eye enucleation within one day after birth has an effect on the postnatal development of substance P (SP)-like-immunoreactive (SP-I) structures in the superior colliculus (SC) was investigated in the rat. Results were compared with those in animals enucleated at postnatal day 15. All the animals were allowed to survive until postnatal day 90, after which changes in SP-I neurons and fibers were identified immunohistochemically. In colchicine-treated rats, the most remarkable changes occurred in SP-I neurons following eye enucleation at birth; large numbers of SP-I neurons appeared in the ventral part of the stratum griseum superficiale (SGS), stratum opticum (SO) and stratum griseum intermediale (SGI) of the deafferentated SC. SP-I neurons did not appear in these layers, when deafferentation of the SC was carried out in rats at postnatal day 15. These findings suggest strongly that eye enucleation at birth affects the production of SP of neurons in the ventral part of the SGS, SO and SGI at the deafferentated SC. The appearance of SP-I neurons in the neonatal eye enucleation may be due, at least partially, to reorganization of another neuronal system in the SC.     

Efficacy of the novel tubulin polymerization inhibitor PTC‐028 for myelodysplastic syndrome

Monomer tubulin polymerize into microtubules, which are highly dynamic and play a critical role in mitosis. Therefore, microtubule dynamics are an important target for anticancer drugs. The inhibition of tubulin polymerization or depolymerization was previously targeted and exhibited efficacy against solid tumors. The novel small molecule PTC596 directly binds tubulin, inhibits microtubule polymerization, downregulates MCL‐1, and induces p53‐independent apoptosis in acute myeloid leukemia cells. We herein investigated the efficacy of PTC‐028, a structural analog of PTC596, for myelodysplastic syndrome (MDS). PTC‐028 suppressed growth and induced apoptosis in MDS cell lines. The efficacy of PTC028 in primary MDS samples was confirmed using cell proliferation assays. PTC‐028 synergized with hypomethylating agents, such as decitabine and azacitidine, to inhibit growth and induce apoptosis in MDS cells. Mechanistically, a treatment with PTC‐028 induced G2/M arrest followed by apoptotic cell death. We also assessed the efficacy of PTC‐028 in a xenograft mouse model of MDS using the MDS cell line, MDS‐L, and the AkaBLI bioluminescence imaging system, which is composed of AkaLumine‐HCl and Akaluc. PTC‐028 prolonged the survival of mice in xenograft models. The present results suggest a chemotherapeutic strategy for MDS through the disruption of microtubule dynamics in combination with DNA hypomethylating agents.