Zinc supplementation during chemotherapy for gynecological malignancy.

OBJECTIVE: To determine the significance of zinc supplementation for zinc deficiency during chemotherapy for gynecologic malignancies. METHODS: Twenty-eight patients suspected of zinc deficiency before chemotherapy were prospectively evaluated. Gustatory test, serum zinc, blood count, and biochemical examinations were made pre-chemotherapy at 3- and 6-week intervals. Patients with serum zinc levels <70 µg were prescribed oral zinc acetate hydrate (167.8 mg/day) for 3 weeks. The primary outcome was efficacy of zinc supplementation, the secondary outcomes were zinc deficiency rates and adverse effects of the zinc supplement. RESULTS: Fifteen (mean serum zinc level: 67.4 ± 6.2 µg/dL) out of 28 patients were administered zinc supplementation pre-chemotherapy, and subsequent serum zinc levels reached 83.2 ± 15.3 µg/dL in 3 weeks. Factors associated with chemotherapy (vs. chemoradiation, p = 0.041) and taxane + platinum (p = 0.048) were significant risk factors for decreasing zinc levels following chemotherapy. Although patients that required zinc supplementation showed decreased serum zinc levels after chemotherapy and tended to experience taste alteration (sour: p = 0.041), zinc supplementation for zinc deficiency during chemotherapy did not alter taste perception. CONCLUSION: Zinc supplementation promptly increased serum levels without major complications and may prevent an alteration in taste perception.

Pheochromocytoma Diagnosed during the Treatment of Diffuse Alveolar Hemorrhage, a Diagnostic Necessity before Using High-dose Glucocorticoids.

A 46-year-old woman with exacerbating hemoptysis and dyspnea was diagnosed with diffuse alveolar hemorrhage (DAH). High doses of glucocorticoids were initiated, but afterward, paroxysmal hypertension (210/140 mmHg) with headache and abdominal pain appeared. A 50-mm left adrenal tumor with an intense uptake by iodine-123 metaiodobenzylguanidine scintigraphy and catecholamine hypersecretion revealed complication with pheochromocytoma. Because high doses of glucocorticoids, sometimes required for DAH, can provoke life-threatening paroxysmal hypertension in pheochromocytoma and paraganglioma (PPGL), our case suggests that PPGL needs to be recognized as the cause of DAH and should be detected with whole-body imaging before starting glucocorticoids.

Radiation-induced gastrointestinal syndrome is exacerbated in vitamin C-insufficient SMP30/GNL knockout mice.

OBJECTIVES: Accidental exposure to high-dose radiation causes life-threatening acute radiation syndrome, features that include gastrointestinal syndrome (GIS) and hematopoietic syndrome (HS). Administration of vitamin C (VC), a free radical scavenger, has been reported to increase survival of mice in GIS and HS models. The effect of nutritional VC status on radiation injury remains unknown because, unlike humans, mice can synthesize VC. The aim of this study was to investigate the effect of VC insufficiency on acute radiation syndrome using senescence marker protein 30 (SMP30)/gluconolactonase knockout (SMP30-KO) mice. METHODS: SMP30-KO mice, which cannot synthesize VC, were given water with or without sufficient VC supplementation, and were analyzed in GIS and HS models. RESULTS: In the GIS model, in which bone marrow failure is rescued by bone marrow transplantation, VC-insufficient mice had a lower survival rate than VC-sufficient mice. The intestine of VC-insufficient GIS mice showed epithelial cell atrophy, inflammatory cell infiltration, and decreased crypt cell proliferation. We observed rapid VC oxidation after total body irradiation in the intestine of mice supplemented with VC-sufficient water. In the HS model, which was not combined with bone marrow transplantation, there was no difference in survival between VC-insufficient and -sufficient mice. CONCLUSION: The results of this study demonstrated that nutritionally sufficient VC exerts a radioprotective effect against radiation-induced GIS.

Elemental Diet Accelerates the Recovery From Oral Mucositis and Dermatitis Induced by 5-Fluorouracil Through the Induction of Fibroblast Growth Factor 2.

Mucositis and dermatitis induced by anticancer agents are common complications of anticancer therapies. In this study, we evaluated the efficacy of Elental (Ajinomoto Pharmaceutical Ltd, Tokyo, Japan), an elemental diet with glutamine in the treatment of 5-fluorouracil (5-FU)-induced oral mucositis and dermatitis in vivo and tried to clarify the underlying mechanisms of its action. Oral mucositis and dermatitis was induced through a combination of 5-FU treatment and mild abrasion of the cheek pouch in hamsters and the dorsal skin in nude mice respectively. These animals received saline, dextrin or Elental suspension (18 kcal/100 g) by a gastric tube daily until sacrifice. Elental reduced oral mucositis and dermatitis more effectively than dextrin in the animal model. Moreover, growth facilitating effects of Elental on HaCaT cells were examined in vitro. MTT assay, wound healing assay, and migration assay revealed that Elental could enhance the growth, invasion, and migration ability of HaCaT. ELISA and Western blotting showed upregulated FGF2 in Elental-treated HaCaT. These findings suggest that Elental is effective for the treatment of mucositis and dermatitis, and may accelerate mucosal and skin recovery through FGF2 induction and reepithelization.

Increased cell proliferation and differential protein expression induced by low-level Er:YAG laser irradiation in human gingival fibroblasts: proteomic analysis.

Erbium-doped yttrium aluminum garnet (Er:YAG) laser treatment has demonstrated favorable wound healing effect after periodontal therapy. One of the reasons may be the positive biological effect of the low-level laser on the irradiated tissues, although the mechanism remains unclear. The aim of this study was to investigate the effect of low-level Er:YAG laser irradiation on cell proliferation and laser-induced differential expression of proteins in human gingival fibroblasts (HGFs) by proteomic analysis. In the first experiment, HGFs were exposed to low-level Er:YAG laser irradiation and the laser-induced cell proliferation and damage were evaluated on day 3. In the second experiment, proteomic analysis was performed on day 1 after irradiation. The peptides prepared from HGFs were analyzed by a hybrid ion trap-Fourier transform mass spectrometer, Mascot search engine, and UniProtKB database. A significant increase in cell proliferation without cell damage after irradiation was observed. Among the total identified 377 proteins, 59 proteins, including galectin-7, which was associated with the process of wound healing, were upregulated and 15 proteins were downregulated in laser-treated HGFs. In the third experiment, the increase in messenger RNA (mRNA) and protein expression of galectin-7 in the irradiated HGFs was validated by various analytical techniques. In addition, the effect of recombinant human galectin-7 on the modulation of HGFs proliferation was confirmed. The results indicate that low-level Er:YAG laser irradiation can promote HGF proliferation and induce a significant change in protein expression and the upregulation of galectin-7 expression may partly contribute to the increase in cell proliferation.

Cryotherapy for massive vulvar lymphatic leakage complicated with lymphangiomas following gynecological cancer treatment.

Vulvar lymphatic leakage is a severe complication associated with gynecological cancer treatments. However, standard treatment strategies have not yet been determined. We encountered a rare case of a 76-year-old multiparous woman suffering from massive lymphatic fluid leakage from the entire vulva, and papules developed and were identified as lymphangiomas. A large amount of straw-colored discharge continued from all vulvar papules, which extended over the mons pubis. Nine years ago, the patient had undergone a radical hysterectomy with concurrent chemoradiation for uterine cervical cancer treatment. Her serum albumin level was 1.9 mg/dl, which was attributed to the loss of a large amount of lymph fluid due to leakage from the vulva. Her quality of life gradually decreased because of general fatigue and the need for frequent diaper exchanges every 2 h. The patient received a less-invasive treatment with cryotherapy using liquid nitrogen. She also received a multimodality treatment consisting of the intravenous administration of albumin, massage of the lower limbs and intensive rehabilitation. Cryotherapy was administered once a week for 3 months. Her discharge almost stopped and vulvar lymphangiomas decreased without any major complications. To the best of our knowledge, this is the first case report of massive lymphatic leakage complicated with vulvar lymphangiomas. Additionally, this case may represent the first successful treatment of vulva lymph leakage by cryotherapy without recurrence. Cryotherapy may have the potential to improve the quality of life as a less-invasive treatment for gynecological cancer survivors without serious complications.

Low-level laser therapy for spinal cord injury in rats: effects of polarization.

The effects of laser polarization on the efficacy of near-infrared low-level laser therapy for spinal cord injury (SCI) are presented. Rat spinal cords were injured with a weight-drop device, and the lesion sites were directly irradiated with a linearly polarized 808-nm diode laser positioned either perpendicular or parallel to the spine immediately after the injury and daily for five consecutive days. Functional recovery was assessed daily by an open-field test. Regardless of the polarization direction, functional scores of SCI rats that were treated with the 808-nm laser irradiation were significantly higher than those of SCI alone group (Group 1) from day 5 after injury. The locomotive function of SCI rats irradiated parallel to the spinal column (Group 3) was significantly improved from day 10 after injury, compared to SCI rats treated with the linear polarization perpendicular to the spinal column (Group 2). There were no significant differences in ATP contents in the injured tissue among the three groups. We speculate that the higher efficacy with parallel irradiation is attributable to the deeper light penetration into tissue with anisotropic scattering.

Characteristics of systolic and diastolic potentials recorded in the left interventricular septum in verapamil-sensitive left ventricular tachycardia.

We studied the electrophysiological characteristics of systolic (SP) and diastolic (DP) potentials recorded during sinus rhythm (SR) in the left interventricular septum of a 27 year-old woman presenting with verapamil-sensitive idiopathic left ventricular tachycardia (VT). During SR, and during VT, SP was activated from ventricular base-to-apex, and DP from apex-to-base. SP and DP were both detected at the site of successful ablation during SR, whereas during VT, DP was detected away from the earliest activation site. Thus, SP apparently reflected a critical component of the reentrant circuit, while DP reflected the activation of a bystander pathway.

Typical atrial flutter with atypical flutter wave morphology due to abnormal interatrial conduction.

We report a case of typical counterclockwise atrial flutter (AFL) with conduction block from right to left atrium along the coronary sinus (CS) musculature, confirmed by discontinuous CS activation sequence during pacing near the ostium and differential right atrial pacing. AFL was associated with an atypical flutter wave morphology, due to the detour of the activation wavefront from right to left atrium via alternate interatrial electrical connections, such as Bachmann's bundle, the interatrial septum, or both.

Molecular cloning, structure, expression, and chromosomal localization of the human Osterix (SP7) gene.

We report the isolation of the human orthologue of the mouse Osterix (Osx/Sp7) gene, a C2H2 zinc finger transcription factor of the SP gene family and putative "master" regulator of bone cell differentiation. The human SP7 cDNA encodes a putative 431 amino acid protein that contains three consecutive C2H2 zinc finger repeats. The SP7 protein is highly conserved between mice and humans with an overall sequence identity of 95%. The expression of a SP7 mRNA transcript of approximately 3.2 kb is restricted to bone-derived cell lines in vitro but undetectable in any adult tissues including mandibular bone by Northern blot hybridization. The specific expression of SP7 mRNA in osteoblasts in vivo was further confirmed by in situ hybridization on human embryonic tissues. The highly restricted expression pattern and the divergence of the sequence outside of the zinc finger region distinguish SP7 as a unique member of the SP family. The SP7 gene consists of two exons, with exon 2 containing most of the protein coding sequence. The gene locus was mapped to chromosome 12q13.13 by fluorescent in situ hybridization (FISH). The identification and initial characterization of the SP7 gene will facilitate the study of the molecular regulation of osteoblast differentiation in humans.