Impact of Physical Stress on Salivary Buffering Capacity

Background: Saliva has many properties and the buffering capacity is important for the neutralization of oral fluids. It is unclear whether stressful conditions directly affect salivary buffering capacity, and we investigated the impact of physical stress on salivary buffering capacity. Methods: Twelve participants were subjected to the physical stress of jogging and running. The salivary buffering capacity and flow rate of the participants were measured before and after exposure to stressful conditions. Salivary α-amylase activity was measured as a quantitative index of stress. Results: No change in buffering capacity was detected among each time point during the whole course under physically stressful conditions. Next, we examined the change in buffering capacity after jogging compared to baseline. Six participants showed an increase in buffering capacity (Group A), while the other six participants showed a decrease or no change (Group B) after jogging. Group B showed a decrease in flow rate and increases in α-amylase activity and protein level after jogging, whereas Group A showed no changes in these properties. Conclusions: The results suggest that salivary buffering capacity changes following exposure to physically stressful conditions, and that the changes are dependent on the stress susceptibility of individuals

癌組織への免疫担当細胞の浸潤と全身性免疫能獲得に及ぼすケモカイン遺伝子導入の効果

共立薬科大学 / 金沢大学薬学部腫瘍免疫の成立には、宿主免疫担当細胞が癌細胞を特異的に認識するステップが必要である。βケモカインに属するMIP-1αは炎症組織から産生され、T細胞、B細胞に対する走化活性化作用、マクロファージの抗腫瘍活性化作用、サイトカインの産生増強作用を有する。本研究では癌細胞にhuMIP-1α遺伝子を導入して、癌細胞に対する宿主免疫担当細胞の走化性を増強させ、抗腫瘍効果や免疫獲得能への効果増強を期待した。免疫系の正常なBALB/cマウスとそれに移植できるcolon26結腸癌細胞を選択して、huMIP-1α遺伝子導入の効果を検討した結果、以下のような新知見が得られた。huMIP-1α遺伝子導入癌細胞のマウスに移植後の増殖度は抑制されており、更にマウスの腫瘍拒絶率は高かった。また、同時に肺転移の抑制効果も見られたが、癌悪液質の改善については無効であった。腫瘍を拒絶したマウスについては、更に親株の移植を行ったところ、全例で腫瘍の増殖は認められず、この癌細胞に対する免疫力を獲得していることが示唆された。更に、我々は、他のケモカインであるMCP-1遺伝子導入癌細胞を用いて、その増殖が免疫調節剤の併用で抑制されることを示した。以上、本研究では癌の生育や腫瘍免疫獲得におけるhuMIP-1αの影響を遺伝子導入癌細胞を使用して検討し、腫瘍ワクチンの実用化の可能性を示すことができた。また効果的な薬物療法を併用することによって、腫瘍の近傍に侵潤したマクロファージを活性化して抗腫瘍効果を誘導できることがわかった。研究課題/領域番号:08672605, 研究期間(年度):1996 – 1997出典：研究課題「癌組織への免疫担当細胞の浸潤と全身性免疫能獲得に及ぼすケモカイン遺伝子導入の効果」課題番号08672605（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-08672605/）を加工して作

小腸吸収細胞膜における抗生物質と Na^+ 輸送の相互関係

金沢大学薬学部研究課題/領域番号60571086, 研究期間(年度):1985出典：研究課題「小腸吸収細胞膜における抗生物質と Na^+ 輸送の相互関係」課題番号60571086（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/grant/KAKENHI-PROJECT-60571086/）を加工して作

ケモカイン遺伝子導入癌細胞の転移と増殖に対するサイトカインネットワークの影響

金沢大学医学部・附属病院・薬剤部我々は、癌細胞と宿主細胞に介在する走化性サイトカインであるケモカイン(chemokine)に注目し、chemokine遺伝子導入癌細胞を用いて増殖と転移における役割解明のための研究を進めた。BALB/cマウスの足蹠に、MCAF、IL-8、LD78のchemokine遺伝子を導入した当該マウス種由来の結腸癌細胞を移植して、腫瘍形成能、転移能、腫瘍へのマクロファジ-(MΦ)浸潤について比較した。その結果、LD78遺伝子導入株で著しい抗腫瘍効果が認められたのに比し、MCAF、IL-8遺伝子株では抗主腫瘍果は認められなかった。また、自然肺転移能はMCAF遺伝子導入株で亢進していた。実験的肺転移モデルでも検討したところ、免疫不全マウス(BALB/c nu/nu,SCID)を用いた場合、MCAF遺伝子導入株の転移が正常マウスり減少して居ることがわかった。このことは、MCAF遺伝子導入癌細胞の接着浸潤の過程にT細胞が関与していることを示唆している。MCAF遺伝子導入株を足蹠に移植後、腫瘍へのMΦ浸潤は初期には著しく増加していたが日を追って減少した。このとき、ELISA法で測定した血清中のMCAF濃度は、in vitroでの解離定数(Kd)値を越えており、かつ走化性と相反して増加していた。一方、LD78遺伝子導入株の癌組織にはapoptosis様の細胞死が起こっていた。LD78遺伝子導入株を拒絶したマウスの反対側の足蹠に親株を再チャレンジしたところ全例が拒絶され、強い全身性免疫能を獲得していることがわかった。以上ケモカイン遺伝子の導入によりマウスに腫瘍免疫が誘導されることが立証された。Effects of chemokine on tumor progression and metastasis were studied. Cachexia-inducing adenocarcinoma cell line cells (colon 26, clone 20) were transfected with either a control plasmid or chemokine (MCAF) cDNA.The production of MCAF reached 1.9 ng/ml in vitro when transfectant cells were cultured at a cell density of 5*10^4 cells/ml for 3 days. Transfection of MCAF cDNA did not affect the growth rate in vitro. Also, MCAF-transfectants formed a similar size of tumors and induced the same degree of cachexia after intra-footpad inoculation as the parental cells. When the primary tumors were resected on the 10th day after inoculation, the incidence rate of spontaneous lung metastasis was less than 20% in both transfectant and parental cells. The number of endothelial cells in the primary tumor rapidly increased from the 10th to the 14th day after inoculation. In accordance with enhanced angiogenesis, the incidence rates of spontaneous metastasis increased when the primary tumors were resected on the 14th day after inoculation. Moreover, spontaneous lung metastases as well as experimental lung metastases were augmented in the animals injected with MCAF-transfectants compared to those injected with parental cells with a concomitant increase of angiogenesis. These results suggested that MCAF may augment the metastatic potential by modulating tumor associated angiogenesis.研究課題/領域番号:06672270, 研究期間(年度):1994 – 1995出典：研究課題「ケモカイン遺伝子導入癌細胞の転移と増殖に対するサイトカインネットワークの影響」課題番号06672270（KAKEN：科学研究費助成事業データベース（国立情報学研究所）） （https://kaken.nii.ac.jp/ja/report/KAKENHI-PROJECT-06672270/066722701995kenkyu_seika_hokoku_gaiyo/）を加工して作

Theobromine enhances the conversion of white adipocytes into beige adipocytes in a PPARγ activation-dependent manner

The adipocytes play an important role in driving the obese-state—white adipose tissue (WAT) stores the excess energy as fat, wherein brown adipose tissue (BAT) is responsible for energy expenditure via the thermoregulatory function of uncoupling protein 1 (UCP1)—the imbalance between these two onsets obesity. Moreover, the anti-obesity effects of brown-like-adipocytes (beige) in WAT are well documented. Browning, the process of transformation of energy-storing into energy-dissipating adipocytes, is a potential preventive strategy against obesity and its related diseases. In the present study, to explore an alternative source of natural products in the regulation of adipocyte transformation, we assessed the potential of theobromine (TB), a bitter alkaloid of the cacao plant, inducing browning in mice (in vivo) and primary adipocytes (in vitro). Dietary supplementation of TB significantly increased skin temperature of the inguinal region in mice and induced the expression of UCP1 protein. It also increased the expression levels of mitochondrial marker proteins in subcutaneous adipose tissues but not in visceral adipose tissues. The microarray analysis showed that TB supplementation upregulated multiple thermogenic and beige adipocyte marker genes in subcutaneous adipose tissue. Furthermore, in mouse-derived primary adipocytes, TB upregulated the expression of the UCP1 protein and mitochondrial mass in a PPARγ ligand-dependent manner. It also increased the phosphorylation levels of PPARγ coactivator 1α without affecting its protein expression. These results indicate that dietary supplementation of TB induces browning in subcutaneous WAT and enhances PPARγ-induced UCP1 expression in vitro, suggesting its potential to treat obesity.ArticleThe Journal of Nutritional Biochemistry. 100: 108898 (2021)journal articl

Physicochemical Properties of Amphoteric β-Lactam Antibiotics. III. Stability, Solubility, and Dissolution Behavior of Cefatrizine and Cefadroxil as a Function of pH

金沢大学大学院自然科学研究科分子作用学金沢大学薬学

Enhancement of Zidovudine Uptake by Dehydroepiandrosterone Sulfate in Rat Syncytiotrophoblast Cell Line TR-TBT 18d-1

ABSTRACT: AZT (3-azido-3-deoxythymidine; zidovudine), which is used for the prevention of mother-to-child transmission of HIV-1, is transplacentally transferred to the fetus across the blood-placenta barrier, which is composed of syncytiotrophoblasts. We recently showed that apical uptake of AZT by syncytiotrophoblasts is mediated by saturable transport system(s) in the TR-TBT 18d-1 cell line, and the cellular accumulation of AZT was increased in the presence of dehydroepiandrosterone sulfate (DHEAS). Here, we aimed to clarify the mechanism of this effect of DHEAS. Inhibitors of efflux transporters, including breast cancer resistance protein, P-glycoprotein, and multidrug resistance proteins, had little effect on the cellular accumulation of AZT in TR-TBT 18d-1. Kinetic study revealed that the rate constant for AZT uptake was greatly increased in the presence of 1 mM DHEAS. These results suggested that the effect of DHEAS was because of enhancement of the uptake process(es), rather than inhibition of efflux. When AZT uptake was analyzed according to the Michaelis-Menten equation, the estimated Michaelis constant, K m , for AZT uptake in the presence of 1 mM DHEAS was lower than that in its absence, whereas maximum uptake velocity, V max , and nonsaturable uptake clearance, k ns , were similar in the presence and absence of DHEAS, indicating that DHEAS may change the recognition characteristics of the transporter for AZT in TR-TBT 18d-1. Thus, the increase of AZT uptake in TR-TBT 18d-1 cells in the presence of DHEAS was concluded to be because of a DHEAS-induced change in the affinity of AZT uptake system, although the transporter responsible for AZT uptake has not been identified