Effects of environmental (cold) stress and aging on cells in monocyte/macrophage lineage were investigated. We demonstrated that immune suppressive states seen in acute cold-stressed mice (8-10 weeks of age) is attributable to FcγRIIbright suppressor macrophages. Serum corticosterone levels were markedly increased in acute cold-stressed mice. In addition, expression of glucocorticoids (GC) receptor mRNA was observed in FcγRIIbright cells from these mice. The increase of FcγRIIbright cells in peritoneal exudate cells caused by acute cold stress was inhibited by adrenalectomy or administration of a saturating amount of the GC antagonist RU 38486 (mifepristone). On the contrary, administration of the GC agonist, dexamethasone, markedly increased the proportion of FcγRIIbright cells in peritoneal exudate cells of control mice. These results suggest that the generation of FcγRIIbright suppressor cells of monocyte/macrophage lineage by acute cold stress was mediated by action of GC through the GC receptor. We likewise found that the proportion of FcγRIIbright suppressor macrophages is increased in aged mice (22-24 months of age). Meanwhile, activated macrophages which function as antigen presenting cells were decreased in aged rats. Both the basal corticosterone concentrations in serum and the expression of mRNA for GC receptor in peritoneal macrophages increased significantly in aged animals, suggesting that these populational and functional changes of macrophages in aged animals were mediated, in part, by the increased basal levels of GC. This is probably being responsible for immunosenescence.
Neisseria gonorrhoeae ; Laboratory mice ; Acute ; Macrophages ; receptor

The combination effects of chloroquine with Cepharanthin^® or minocycline hydrochloride were evaluated against a blood-induced infection with chloroquine-resistant P. berghei NK 65 in ICR mice. The infected mice in an untreated control group showed a progressively increasing parasitemia leading to mouse death. A two-day dosage of 20 mg base/kg of chloroquine alone produced little effect against P. berghei NK 65 infection, and all mice died from day 13 to 15 with an increasing parasitemia. A four-day dosage of 4 mg/kg of Cepharanthin^® alone produced no antimalarial activity, and all mice died by day 10. A four-day dosage of 50 mg/kg of minocycline hydrochloride alone produced a slight effect, but all mice died by day 18. Furthermore, mice given chloroquine in combination with Cepharanthin^® died from day 14 to 15. Mice given Cepharanthin^® plus minocycline hydrochloride also died from day 15 to 17. On the other hand, infected mice treated with chloroquine plus minocycline hydrochloride survived during the experiment. All mice treated with chloroquine alone, minocycline hydrochloride alone, chloroquine plus Cepharanthin^® or Cepharanthin^® plus minocycline hydrochloride showed low parasitemia levels during drug administration and a few subsequent days, but then malaria parasites re-increased in the bloodstream of the treated mice until death. On the other hand, malaria parasites in the mice given chloroquine plus minocycline hydrochloride decreased on day 6 and then could not be detected by microscopic examination during the observation period. This finding strongly suggests that the combination effects of chloroquine and minocycline hydrochloride are worthy of evaluation in human malaria. The results also clearly demonstrate the necessity and importance of in vivo experiments in estimating the activities of drugs.

[Aim] Diffuse pan-bronchiolitis (DPB) causes severe respiratory dysfunction and severely limits a patient's daily activities. Case: This paper reports a case of a DPB patient whose respiratory symptoms were successfully improved by acupuncture. In a case report in January 2002, a 62-year-old male visited the Department of Respiratory Internal Medicine at Gifu University Hospital, complaining of cough, pumlent sputum and dyspnea on exercise. His general condition had worsened despite ordinary medical treatment. Thus acupuncture was added to the treatment in August, 2001. Intervention: The patient received acupuncture treatments once a week for 50 weeks. The acupuncture treatment was based on the Chinese medicine theory. Measurements: Outcome measures were respiratory symptoms using the Fletcher-Hugh-Jones (F-H-J) classification, 6-minute walking distance (6 MWD), blood test, arterial blood gas and pulmonary function tests. Computed tomography (CT) was assessed. Each evaluation was done after 15 weeks and 50 weeks later.
[Results] After 15 weeks of acupuncture treatment, cough, pumlent sputum, walking distance, the Borg scale and respiratory function were significantly improved compared with the baseline. Moreover, the effect of the acupuncture treatment continued for 50 weeks.
[Conclusion] This suggests that acupuncture treatment was effective in treating the advanced case of DPB.

OBJECTIVES: Increasing bone mineral density (BMD) to reduce fracture risk is a primary goal of osteoporosis treatment. This prospective, observational study evaluates the effects of monthly minodronate (MIN; 50 mg) with or without eldecalcitol (ELD) addition in osteoporosis patients with rheumatoid arthritis (RA) during 18 months. METHODS: The cohort was prospectively and randomly split into the MIN monotherapy group (14 cases) and MIN plus ELD group (combination group; 14 cases) due to no reports on the effectiveness and safety of MIN therapy in relation to ELD addition for comparisons of serum tartrate-resistant acid phosphatase (TRACP)-5b, bone alkaline phosphatase (BAP), and BMD of the lumbar 1–4 vertebrae (L-BMD), bilateral total hips (H-BMD; the mean value of the right and left hips), and bilateral femoral necks (FN-BMD) at baseline and at 6, 12, and 18 months of treatment. RESULTS: Baseline values were comparable between the groups apart from a tendency for higher TRACP5b in the combination group. Seven of 14 patients in the combination group had received previous bisphosphonate treatment. BAP was significantly more reduced in the monotherapy group at 6 months, with no other remarkable differences for TRACP5b, L-BMD, H-BMD, or FN-BMD during the observation period. CONCLUSIONS The above findings suggest that regardless of ELD addition, MIN potentially improves BMD during 18 months in osteoporosis patients with RA.

OBJECTIVES: The aim of this study was to examine the efficacy, safety, and adherence of ibandronate (IBN) treatment with or without vitamin D supplementation for 3 years in Japanese women with postmenopausal osteoporosis. METHODS: This prospective investigation included 27 patients treated with IBN alone (monotherapy group) and 29 patients receiving IBN and alfacalcidol (ALF) (combination group). Bone metabolism and bone mineral density (BMD) were measured before and at 18, 24, 30, and 36 months of therapy. Treatment discontinuation and fracture occurrence were assessed as well. RESULTS: Lumbar 1–4 BMD (L-BMD) was significantly increased in the monotherapy and combination groups by 3.9% and 7.2%, respectively, at 36 months, with significant gains in total hip BMD (H-BMD) of 3.7% and 4.9%, respectively. There were significant differences in L-BMD improvement between the groups at 18, 24, and 30 months (P < 0.05) and at 36 months (P < 0.01). Compared with pretreatment levels, the percentage changes of L-BMD and H-BMD were significant at all time points in the combination group and at all points apart from L-BMD at 36 months in the monotherapy group. In the monotherapy group, 14 patients dropped out during 3 years and 2 vertebral fractures occurred during the first year. In the combination group, 16 cases dropped out during 3 years and 1 nonvertebral fracture was noted during the first year. CONCLUSIONS: Our findings suggest that combination therapy of IBN and vitamin D is superior to monotherapy with regard to L-BMD improvements for 3 years, with both groups showing comparable safety and adherence to treatment.
Asian Continental Ancestry Group ; Bone Density ; Compliance ; Female ; Hip ; Humans ; Metabolism ; Osteoporosis ; Osteoporosis, Postmenopausal ; Prospective Studies ; Vitamin D

OBJECTIVES: The aim of this study was to examine the discontinuation and occurrence of fracture during denosumab treatment in Japanese women with primary osteoporosis or rheumatoid arthritis (RA) with osteoporosis. METHODS: This retrospective study included 143 patients with primary osteoporosis and 96 patients with RA and osteoporosis who were treated with denosumab. Treatment discontinuation, fracture occurrence, lumbar spine (L1–4) bone mineral density (LS-BMD), and bilateral total hip BMD (TH-BMD) were examined before and at 1 and 2 years after treatment commencement. RESULTS: In the primary osteoporosis group, 32 cases dropped out and no fractures occurred from 0 to 1 year. Eighteen cases were lost to follow-up and no fractures were noted from 1 to 2 years. In the RA with osteoporosis group, 7 cases dropped out and no fracture occurred from 0 to 1 year. Twenty-one cases were lost to follow-up and 2 nonvertebral fractures were noted from 1 to 2 years. In this group, 13 cases dropped out from 1 to 2 years and 16 cases dropped out during the 2-year study period due to economic reasons. LS-BMD and TH-BMD values increased continuously for 2 years of treatment in both primary osteoporosis and RA with osteoporosis groups. CONCLUSIONS: These results suggest that during denosumab therapy, the discontinuation rate is expected to remain low during 2 years of treatment in primary osteoporotic patients. In RA patients with osteoporosis, however, the discontinuation rate may increase due to economic reasons from 1 to 2 years of therapy.
Arthritis, Rheumatoid* ; Asian Continental Ancestry Group* ; Bone Density ; Compliance* ; Denosumab* ; Female ; Hip ; Humans ; Lost to Follow-Up ; Osteoporosis* ; Retrospective Studies ; Spine

AIMTo evaluate the occurrence and prevalence of microdeletions in the gamma chromosome of patients with azoospermia.

METHODSDNA from 29 men with idiopathic azoospermia was screened by polymerase chain reaction (PCR) analysis with a set of gamma chromosome specific sequence-tagged sites (STSs) to determine microdeletions in the gamma chromosome.

RESULTSDeletions in the DAZ (deleted in azoospermia) loci sgamma254 and sgamma255 were found in three patients with idiopathic azoospermia, resulting in an estimated frequency of deletions of 10.7% in idiopathic azoospermia men.

CONCLUSIONWe conclude that PCR analysis is useful for the diagnosis of microdeletions in the Y chromosome, which is important when deciding the suitability of a patient for assisted reproductive technology such as testicular sperm extracion-intracytoplasmic sperm injection (TESE-ICSI).

Adult ; Base Sequence ; Chromosomes, Human, Y ; DNA Primers ; Euchromatin ; genetics ; Follicle Stimulating Hormone ; blood ; Heterochromatin ; genetics ; Humans ; Luteinizing Hormone ; blood ; Male ; Oligospermia ; blood ; etiology ; genetics ; Polymerase Chain Reaction ; Prolactin ; blood ; Sequence Deletion ; genetics ; Sequence Tagged Sites ; Testosterone ; blood

Objective: Anticancer drugs have carcinogenic potential and are associated with occupational exposure risks among healthcareprofessionals who handle them. To minimize occupational exposure, healthcare workers must be adequately aware of the risks ofanticancer drugs and the appropriate techniques for their preparation. However, there is little information on the awareness ofpharmacists who prepare anticancer drugs in medical settings. The aim of this study was to investigate awareness of hazardous drugs(HD) and appropriate preparation techniques among pharmacists, and identify problems that pharmacists experience in managing theirexposure to anticancer drugs.Design: Questionnaire.Method: The questionnaire was sent by e-mail or mail to pharmacists employed at 270 institutions who belonged to the Chiba Societyof Hospital Pharmacists. From September 2015 to March 2016, respondents completed the questionnaires voluntarily and returnedthem by mail. Returning the questionnaire was regarded as informed consent to participate in this survey. Based on the completedquestionnaires, we examined the awareness of pharmacists in their daily work.Results: In total, 218 questionnaires were returned (collection rate: 10%). Awareness of the risks of anticancer drugs was high, and ahigh percentage of respondents use personal protective equipment during drug preparation, but the use of closed system drug transferdevices was low. Overall, however, it was found that many pharmacists had insufficient understanding of safe handling techniques.Discussion: Despite some recognition of the risks associated with exposure to HD, the measures taken to prevent exposure toHDs―including anticancer drugs―were inadequate and this issue must be urgently addressed by medical institutions and pharmacists.Countermeasures such as training sessions in the handling of HDs and the development of manuals are needed for each facility.