Correlation between blood magnesium and calcium concentration in patients treated with an anti-EGFR antibody.

BACKGROUND: Hypomagnesemia is one of the characteristic side effects of the human anti-epidermal growth factor receptor (EGFR) monoclonal antibodies, cetuximab and panitumumab. The major mechanism of anti-EGFR antibody-related hypomagnesemia is suppression of EGFR-mediated urinary Mg(2+) reabsorption in both the renal tubule the intestinal tract. Since Mg(2+) is known to affect blood Ca(2+) levels through regulation of parathyroid hormone (PTH) secretion, we investigated the correlation between Ca(2+) and Mg(2+) concentration in blood. METHODS: Between April 2012 and October 2015, blood Mg(2+) and Ca(2+) concentrations (albumin corrected value) of 22 colon cancer patients undergoing treatment with either cetuximab or panitumumab at Toyooka Public Hospital were measured simultaneously. RESULTS: Hypomagnesemia (of all Grades) was reported in 13 of 22 patients. Two patients had hypomagnesemia of severity > Grade 3. Changes in blood Mg(2+) and Ca(2+) concentration showed a significant correlation (r(2) = 0.7455), which could be expressed using the following equation, Ca(2+) concentration = 1.4268 × (Mg(2+) concentration) + 7.1126. CONCLUSION: Since the early stages of hypomagnesemia produce no characteristic clinical symptoms, it is easily overlooked until it becomes severe. The investigation results suggest that if low blood Ca(2+) concentration (mg/dL) is observed in patients administered anti-EGFR antibodies, early evaluation of blood Mg(2+) concentration (mg/dL) and prompt supportive care are required to prevent aggravation of hypomagnesemia.

Polaprezinc attenuates cyclophosphamide-induced cystitis and related bladder pain in mice.

Cav3.2 T-type Ca(2+) channels targeted by H2S, a gasotransmitter, participate in cyclophosphamide-induced cystitis and bladder pain. Given that zinc selectively inhibits Cav3.2 among T-channel isoforms and also exhibits antioxidant activity, we examined whether polaprezinc (zinc-l-carnosine), a medicine for peptic ulcer treatment and zinc supplementation, reveals preventive or therapeutic effects on bladder inflammation and/or pain in the mouse with cyclophosphamide-induced cystitis, a model for interstitial cystitis. Systemic administration of cyclophosphamide caused cystitis-related symptoms including increased bladder weight and vascular permeability, and histological signs of bladder edema, accompanied by bladder pain-like nociceptive behavior/referred hyperalgesia. All these symptoms were significantly attenuated by oral preadministration of polaprezinc at 400 mg/kg. The same dose of polaprezinc also prevented the increased malondialdehyde level, an indicator of lipid peroxidation, and protein upregulation of cystathionine-γ-lyase, an H2S-generating enzyme, but not occludin, a tight junction-related membrane protein, in the bladder tissue of cyclophosphamide-treated mice. Oral posttreatment with polaprezinc at 30-100 mg/kg reversed the nociceptive behavior/referred hyperalgesia in a dose-dependent manner without affecting the increased bladder weight. Together, our data show that zinc supplementation with polaprezinc prevents the cyclophosphamide-induced cystitis probably through the antioxidant activity, and, like T-channel blockers, reverses the established cystitis-related bladder pain in mice, suggesting novel therapeutic usefulness of polaprezinc.

Design of hemispherical radio frequency (RF) capacitive-type electrode free of edge effects for treatment of intracavitary tumors.

A new hemispherical electrode to heat oral cavity cancer is proposed. The electrode does not produce a hot spot around its edge, a feature that usually arises when using radio frequency (RF) capacitive-type heating. The hemispherical electrode was designed by computer simulation using a 3-D finite element method. To assess its practicality and effectiveness, we built a prototype hemispherical electrode and evaluated its heating characteristics by phantom experiments. The heating effects on the phantom were measured by thermography. The concave phantom surface in contact with the hemispherical electrode showed a uniform increase in temperature, with no obvious edge effect. The proposed electrode allows non-invasive RF capacitive-type heating for intracavity tumors that was not previously considered possible, and should contribute to the multidisciplinary treatment of intracavity tumors.

[Effectiveness of methotrexate for the escape by salazosulfapyridine].

Although disease modifying anti-rheumatic drugs (DMARDs) are used in the treatment of rheumatoid arthritis (RA), the selection of agents in the case of relapse (escape phenomenon) lacks clear-cut standards. We compared the effectiveness in a salazosulfapyridine and then methotrexate (SASP-->MTX) group with that in the mothotrexate (SASP+MTX) group after escape phenomenon expression in C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) data. Outpatients of the Matsubara Mayflower Hospital with a history of DMARD administration during the 4 years prior to May 2003 were studied. The CRP level in the SASP-->MTX group (n=8) after the escape phenomenon expression showed a decline after 3 months, but no decline was seen even after 3 months the two in the CRP level in the SASP+MTX group (n=10). However, the difference between groups was not significant. The fluctuation in ESR was similar to that in CRP. However, ESR was significantly lower in the SASP-->MTX group 20 weeks after escape phenomenon expression. In evaluating treatment effectiveness after escape phenomenon expression in each group, SASP-->MTX was effective in 10 and SASP+MTX in 7 patients. Side effects necessitated cessation of treatment in 1 patient in the SASP-->MTX group. Treatment continued in 4 patients in the SASP-->MTX group and 2 in the SASP+MTX group, even though side effects occurred. It should be borne in mind that combination therapy often has greater clinical benefit than single agent therapy but not always.

[Examination of the escape phenomenon in disease modifying antirheumatic drugs].

Although disease-modifying antirheumatic drugs (DMARDs) are used in the treatment of rheumatoid arthritis (RA), the selection of agents in the case of relapse (escape phenomenon) lacks clear-cut standards. Therefore we investigated the rate and conditions of escape as well as the agents used after escapes had occurred. Outpatients of the Matsubara Mayflower Hospital with a history of DMARD administration during the 4 years prior to May 2003 were studied. Those receiving salazosulfapyridine (SASP) had a high escape rate and those receiving methotrexate (MTX) and bucillamine (BC) had a low rate. The continuous duration of administration was long for MTX and BC, but short for sodium aurothiomalate (GST). BC and Actarit (AR) gradually elevated C-reactive protein (CRP) levels and the erythrocyte sedimentation rate (ESR). In patients receiving SASP and MTX, a high level of CRP and high ESR was seen 2 months prior to the occurrence of escape and remained unchanged after escape. With respect to the agents used after escape, SASP and BC were substituted with other DMARDs. A combination with other DMARDs was usually administered to patients who had been receiving MTX. Taken together, the present results clarified the characteristics of DMARD escape and will contribute to the appropriate pharmacotherapy for RA.

Engineering of polyploid Saccharomyces cerevisiae for secretion of large amounts of fungal glucoamylase.

We engineered Saccharomyces cerevisiae cells that produce large amounts of fungal glucoamylase (GAI) from Aspergillus awamori var. kawachi. To do this, we used the delta-sequence-mediated integration vector system and the heat-induced endomitotic diploidization method. delta-Sequence-mediated integration is known to occur mainly in a particular chromosome, and the copy number of the integration is variable. In order to construct transformants carrying the GAI gene on several chromosomes, haploid cells carrying the GAI gene on different chromosomes were crossed with each other. The cells were then allowed to form spores, which was followed by dissection. Haploid cells containing GAI genes on multiple chromosomes were obtained in this way. One such haploid cell contained the GAI gene on five chromosomes and exhibited the highest GAI activity (5.93 U/ml), which was about sixfold higher than the activity of a cell containing one gene on a single chromosome. Furthermore, we performed heat-induced endomitotic diploidization for haploid transformants to obtain polyploid mater cells carrying multiple GAI genes. The copy number of the GAI gene increased in proportion to the ploidy level, and larger amounts of GAI were secreted.