Repair of potentially lethal damage by total and quiescent cells in solid tumors following a neutron capture reaction

Purpose: We analyzed the time-course of changes in the sensitivity of total (proliferating + quiescent and quiescent (Q) cell populations within solid tumors in situ following a neutron capture reaction and compared it with that after γ-ray irradiation. Methods: After continuous labeling of proliferating cells with BrdU for 5 days, mice bearing SCC VII tumors received thermal neutron irradiation with or without a ¹⁰B-labeled compound (sodium [¹⁰B]borocaptate, BSH, or dl-p-[¹⁰B]boronophenylalanine, BPA), or γ-ray irradiation. From 5 min to 72 h after treatment, tumors were excised, minced, and trypsinized. Cell suspensions were incubated for 48 h with the cytokinesis blocker cytochalasin-B. The micronucleus frequency for BrdU-unlabeled cells, Q cells at treatment, was then determined by immunofluorescence staining for BrdU. The micronucleus frequency for total cells was obtained from tumors that had not been pretreated with BrdU labeling. The sensitivity was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (micronucleus frequency). Results: Overall, Q cells showed greater repair capacities than total cells. γ-Ray irradiation and neutron irradiation with BPA induced larger repair capacities in each cell population. In contrast, thermal neutron irradiation without a ¹⁰B-labeled compound induced the smallest repair capacity in both cell populations. The use of a ¹⁰B-labeled compound, especially BPA, widened the difference in sensitivity between total and Q cells, resulted in an increase in repair capacity in both cell populations, and made the repair patterns of the two cell populations look like those induced by γ-ray irradiation. Conclusion: Differences in sensitivity and repair patterns following the neutron capture reaction were thought to depend on differences in the distribution of the ¹⁰B-labeled compound between the proliferating and Q cell populations. Received: 18 February 1999 / Accepted: 4 June 1999     

Pathological fractures due to intraosseous fat necrosis associated with pancreatitis

SIR, Necrosis of fatty bone marrow is an unusual complicationof severe pancreatic disorders. We describe a patient presentingwith multiple pathological fractures associated with alcoholicpancreatitis. A 76-yr-old man was admitted to our hospital in May 2000 forpain and swelling of the right hand, both feet and     

The role of the renal dopaminergic and the prostaglandin systems in renal uric acid metabolism in patients with essential hypertension]

The present study aimed to elucidate the role of renal dopaminergic and prostaglandin (PG) systems in renal uric acid metabolism in essential hypertension. Mean arterial pressure (MAP), heart rate (HR), endogenous creatinine clearance (Ccr), serum uric acid (SUA), urinary excretions of uric acid (UUAV) and sodium (UNaV), fractional excretions of uric acid (FEUA) and sodium (FENa), plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured before and after intravenous injection of a dopamine receptor antagonist, metoclopramide (MCP: 8 mg/m2.BSA), or before and after a single oral administration of prostaglandin synthesis inhibitor, indomethacin (IM: 75 mg), in 34 mild-to-moderate essential hypertensives (EHT). MCP injection or acute oral administration of IM caused significant decreases of UNaV and FENa in each group, whereas MAP, HR and SUA did not change in either group. Significant decreases in Ccr, UUAV and FEUA and increases in PRA and PAC were demonstrated by MCP injection, while no significant changes in these parameters were revealed by IM administration. There was a significant positive correlation between delta UUAV and delta Ccr or delta FEUA in both groups. In addition, a close positive correlation between delta UUAV and delta UNaV as well as between delta FEUA and delta FENa was found in the MCP group, but not in the IM group. On the other hand, no significant correlation was observed between delta UUAV and delta PRA or delta PAC in either MCP or IM administration. The decreases of UUAV and FEUA were significantly greater in MCP than in IM administration, despite similar changes in Ccr, UNaV and FENa between the two procedures. These data suggest that the endogenous renal dopaminergic system may contribute to renal uric acid metabolism, which is rather closely related to sodium handling in essential hypertension than the prostaglandin system. Furthermore, the attenuated renal dopaminergic activity may contribute to the elevation of serum uric acid level in patients with essential hypertension.     

Decreased calcitonin gene-related peptide expression in the dorsal root ganglia of TNF-deficient mice in a monoiodoacetate-induced knee osteoarthritis model

Background: The detailed mechanisms of knee osteoarthritis (OA) pain have not been clarified, but involvement of inflammatory cytokines such as tumor necrosis factor-alpha (TNF) has been suggested. The present study aimed to investigate the more detailed neurological involvement of TNF in joint pain using a TNF-knockout mouse OA model. Methods: The right knees of twelve-week-old C57BL/6J wild and TNF-deficient knockout (TNF-ko) mice (n=15, each group) were given a single intra-articular injection of 10 µg monoiodoacetate in 10 mL sterile saline. The left knees were only punctured as the control. Evaluations were performed immediately after the injection (baseline) and at 7, 14, and 28 days after the injection with a subsequent intra-articular injection of neurotracer into both knees. The animals were evaluated for immunofluorescence of the lumbar dorsal root ganglia (DRG) innervating the knee joints. The injected knees were observed macroscopically and mouse pain-related behaviors were scored. Results: Macroscopic observation showed similar knee OA development in both wild and TNF-ko mice. Calcitonin gene-related peptide (CGRP, a neuropeptide identified as a inflammatory pain-related biomarker) was significantly increased in DRG neurons innervating OA-induced knee joints with significantly less CGRP expression in TNF-ko animals. Pain-related behavior scoring showed a significant increase in pain in OA-induced joints, but there was no significant difference in pain observed between the wild and TNF-ko mice. Conclusions: The result of the present study indicates the possible association of TNF-alpha in OA pain but not OA development.     

In Vivo Curative and Protective Potential of Orally Administered 5-Aminolevulinic Acid plus Ferrous Ion against Malaria

5-Aminolevulinic acid (ALA) is a naturally occurring amino acid present in diverse organisms and a precursor of heme biosynthesis. ALA is commercially available as a component of cosmetics, dietary supplements, and pharmaceuticals for cancer diagnosis and therapy. Recent reports demonstrated that the combination of ALA and ferrous ion (Fe²⁺) inhibits the in vitro growth of the human malaria parasite Plasmodium falciparum. To further explore the potential application of ALA and ferrous ion as a combined antimalarial drug for treatment of human malaria, we conducted an in vivo efficacy evaluation. Female C57BL/6J mice were infected with the lethal strain of rodent malaria parasite Plasmodium yoelii 17XL and orally administered ALA plus sodium ferrous citrate (ALA/SFC) as a once-daily treatment. Parasitemia was monitored in the infected mice, and elimination of the parasites was confirmed using diagnostic PCR. Treatment of P. yoelii 17XL-infected mice with ALA/SFC provided curative efficacy in 60% of the mice treated with ALA/SFC at 600/300 mg/kg of body weight; no mice survived when treated with vehicle alone. Interestingly, the cured mice were protected from homologous rechallenge, even when reinfection was attempted more than 230 days after the initial recovery, indicating long-lasting resistance to reinfection with the same parasite. Moreover, parasite-specific antibodies against reported vaccine candidate antigens were found and persisted in the sera of the cured mice. These findings provide clear evidence that ALA/SFC is effective in an experimental animal model of malaria and may facilitate the development of a new class of antimalarial drug.     

Effect of early mobilization on discharge disposition of mechanically ventilated patients

[Purpose] The purpose of this study was to clarify the benefits of early mobilization for mechanically ventilated patients for their survival to discharge to home from the hospital. [Subjects and Methods] Medical records were retrospectively analyzed of patients who satisfied the following criteria: age ≥ 18 years; performance status 0–2 and independent living at their home before admission; mechanical ventilation for more than 48 h; and survival after mechanical ventilation. Mechanically ventilated patients in the early mobilization (EM) group (n = 48) received mobilization therapy, limb exercise and chest physiotherapy, whereas those in the control group (n = 60) received bed rest alone. Univariate and multivariate logistic regression analyses were performed to identify clinical variables associated with discharge disposition. [Results] Early mobilization was a positive independent factor and the presence of neurological deficits was a negative factor contributing to discharge to home. Among patients surviving mechanical ventilation without neurological deficits, the rate of discharge to home was significantly higher among patients in the EM group that in the control group (76% vs. 40%). [Conclusion] Early mobilization can improve the rate of discharge to home of patients requiring mechanical ventilation because of non-neurological deficits.Key words: Mechanical ventilation, Early mobilization, Physiotherapy