Noninvasive monitoring of deterioration in skeletal muscle function with forearm cast immobilization and the prevention of deterioration

BACKGROUND: In this research inactivity was simulated by immobilizing the forearm region in a plaster cast. Changes in skeletal muscle oxidative function were measured using near-infrared spectroscopy (NIRS), and the preventative effect of the training protocol on deterioration of skeletal muscle and the clinical utility of NIRS were examined. METHODS: Fourteen healthy adult men underwent immobilization of the forearm of the non-dominant arm by plaster cast for 21 days. Eight healthy adult subjects were designated as the immobilization group (IMM) and six were designated as the immobilization + training group (IMM+TRN). Grip strength, forearm circumference and dynamic handgrip exercise endurance were measured before and after the 21-day immobilization period. Using NIRS, changes in oxidative function of skeletal muscles were also evaluated. Muscle oxygen consumption recovery was recorded after the completion of 60 seconds of 40% maximum voluntary contraction (MVC) dynamic handgrip exercise 1 repetition per 4 seconds and the recovery time constant (TcVO(2)mus) was calculated. RESULTS: TcVO(2)mus for the IMM was 59.7 ± 5.5 seconds (average ± standard error) before immobilization and lengthened significantly to 70.4 ± 5.4 seconds after immobilization (p < 0.05). For the IMM+TRN, TcVO(2)mus was 78.3 ± 6.2 seconds before immobilization and training and shortened significantly to 63.1 ± 5.6 seconds after immobilization and training (p < 0.05). CONCLUSIONS: The training program used in this experiment was effective in preventing declines in muscle oxidative function and endurance due to immobilization. The experimental results suggest that non-invasive monitoring of skeletal muscle function by NIRS would be possible in a clinical setting

Dynamics of cellular immune responses in the acute phase of dengue virus infection.

In this study, we examined the dynamics of cellular immune responses in the acute phase of dengue virus (DENV) infection in a marmoset model. Here, we found that DENV infection in marmosets greatly induced responses of CD4/CD8 central memory T and NKT cells. Interestingly, the strength of the immune response was greater in animals infected with a dengue fever strain than in those infected with a dengue hemorrhagic fever strain of DENV. In contrast, when animals were re-challenged with the same DENV strain used for primary infection, the neutralizing antibody induced appeared to play a critical role in sterilizing inhibition against viral replication, resulting in strong but delayed responses of CD4/CD8 central memory T and NKT cells. The results in this study may help to better understand the dynamics of cellular and humoral immune responses in the control of DENV infection

Ultrasonographic Evaluation of Thymus in Holstein Calves and Heifers and its Diagnostic Application

This study was performed to evaluate the cross section of the thymus in 46 clinically healthy Holstein calves and heifers from birth to 100 weeks of age and 8 age-matched affected animals with chronic bronchopneumonia by ultrasonography. The cross sectional area of the thymus increased in healthy calves and heifers from birth to 31 weeks of age, peaked around 35 weeks of age, and then decreased until 100 weeks after birth. A positive correlation (r= 0.74, P<0.05) was found between the area in cross section and the weight of the whole thymus in calves and heifers with chronic bronchopneumonia. The cross- sectional areas of the thymus were significantly (P<0.05) lowered in animals with chronic bronchopneumonia. The cross sections of thymus in clinically healthy calves at 2 weeks of age and heifers at 34 weeks and 87 weeks of age were hypoechoic, moderately hyperechoic and hyperechoic, respectively. The observation of thymus by ultrasonography seems to be an effective tool for estimating the size of the thymus objectively in Holstein calves and heifers from birth to 100 weeks of age. The results of this study prove the approach to be useful and applicable to monitor the growth of thymus in Holstein calves and heifers and their association with chronic pneumonia

Evaluation of the effects of antiepileptic drugs on folic acid uptake by human placental choriocarcinoma cells

Folate status during pregnancy is important for fetal development and health. The placenta plays an important role in supplying the fetus with folate. Most women with epilepsy continue their medication during pregnancy. In the present study, we aimed to evaluate the effects of 16 antiepileptic drugs, clinically used for treatment of epilepsy, on folic acid uptake in two in vitro placental models, BeWo and JEG-3 cells. Short-term exposure to antiepileptic drugs had no effects on [H-3]-folic acid uptake by BeWo cells. However, long-term exposure (24 h) to valproic acid (VPA) increased [H-3]-folic acid uptake by BeWo and JEG-3 cells. VPA treatment for 24 h increased folate receptor-alpha (FR alpha) and proton-coupled folate transporter (PCFT) mRNA expression; however, it did not affect reduced folate carrier expression. These results suggested that the increase in folic acid uptake after exposure to VPA can be attributed to the induction of FR alpha and PCFT expression. Furthermore, the present study showed that exposure to clinical concentrations of oxcarbazepine and stiripentol reduced the viability of BeWo cells. Therefore, the findings of the present study may contribute to better understanding of the mechanisms of toxicity of antiepileptic drugs, and estimation of their potential risk to fetus

Effects of single and repetitive valproic acid administration on the gene expression of placental transporters in pregnant rats : An analysis by gestational period.

The use of valproic acid (VPA), an antiepileptic drug, during pregnancy, is known to increase various fetal risks. Since VPA has been known to inhibit histone deacetylases (HDACs); its administration could alter gene transcription levels. However, in vivo effects of VPA administration on placental transporters have not been fully elucidated. The purpose of the present study was to comprehensively evaluate the effects of single and repetitive VPA administration on the expression of placental transporters and analyze them by gestational day. We investigated 18 transporters (8 ATP-binding cassette (ABC) and 10 solute carrier (SLC) transporters) in the placentas of pregnant rats that were orally administered 400 mg/kg/day VPA for one or four days, during mid- or late gestation. In the control rats, 4 ABC transporter genes (Abcb1a, 1b, Abcc2, Abcc4) were upregulated, 3 (Abcc3, Abcc5, Abcg2) downregulated through gestation, whereas 1 (Abcc1) was not changed. Regarding SLC transporters, 6 genes (Slc7a5, Slc16a3, Slc22a3, Slc22a4, Slco2b1, Slco4a1) were increased, 1 (Slc29a1) decreased through gestation, whereas 3 (Slc7a8, Slc22a5, Slco2a1) showed no significant change. Single VPA administration altered the expression of 9 transporters and repetitive administration, 13 transporters. In particular, VPA remarkably decreased Abcc4 and Slc22a4 in late gestation and increased Abcc5 during mid-gestation. Our findings indicated that VPA administration changed transporter expression levels in rat placenta, and suggested that sensitivity to VPA differs across gestational stages