Temperature changes caused by the difference in the distance between the ultrasound transducer and bone during 1†mhz and 3†mhz continuous ultrasound: a phantom study.

[Purpose] This study aimed to use a thermograph to observe temperature changes caused by different distances between an ultrasound transducer and bone during 1 MHz and 3 MHz continuous ultrasound emission on a phantom. [Materials and Methods] We observed the distribution of temperature elevations on a phantom consisting of pig ribs and tissue-mimicking material. One megahertz and 3 MHz ultrasound were delivered at 2.0 W/cm(2) for 5 minutes. To record the temperature changes on the phantom, we took a screenshot of the thermograph with a digital camera every 20 seconds. [Results] With 1 MHz ultrasound at the distances of 2 and 3 cm, the temperature elevation near the bone was higher than that near the transducer. However, with 3 MHz ultrasound, the temperature elevation was higher near the transducer rather than near the bone. At this point, we consider that there is a possibility of heat injury to internal organs in spite of there being no elevation of skin temperature. [Conclusion] When performing ultrasonic therapy, not only should the frequency be taken into consideration, but also the influence of the absorption coefficient and the reflection of the tissue. We visually confirmed the thermal ultrasound effect by thermography. Special attention to the temperature elevation of the internal organs is necessary to avoid injuries.

Effects of edaravone, a free radical scavenger, on photochemically induced cerebral infarction in a rat hemiplegic model.

Edaravone is a free radical scavenger that protects the adjacent cortex during cerebral infarction. We created a hemiparetic model of cerebral thrombosis from a photochemically induced infarction with the photosensitive dye, rose bengal, in rats. We examined the effects of edaravone on recovery in the model. A total of 36 adult Wistar rats were used. The right sensorimotor area was irradiated with green light with a wavelength of 533 nm (10 mm diameter), and the rose bengal was injected intravenously to create an infarction. The edaravone group was injected intraperitoneally with edaravone (3 mg/kg), and the control group was injected with saline. The recovery process of the hemiplegia was evaluated with the 7-step scale of Fenny. The infarcted areas were measured after fixation. The recovery of the paralysis in the edaravone-treated group was significantly earlier than that in the untreated group. Seven days later, both groups were mostly recovered and had scores of 7, and the infarction region was significantly smaller in the edaravone-treated group. Edaravone reduced the infarction area and promoted the functional recovery of hemiparesis from cerebral thrombosis in a rat model. These findings suggest that edaravone treatment would be effective in clinical patients recovering from cerebral infarction.

The effect of anabolic steroid administration on passive stretching-induced expression of mechano-growth factor in skeletal muscle.

BACKGROUND: Stretching of skeletal muscle induces expression of the genes which encode myogenic transcription factors or muscle contractile proteins and results in muscle growth. Anabolic steroids are reported to strengthen muscles. We have previously studied the effects of muscle stretching on gene expression. Here, we studied the effect of a combination of passive stretching and the administration of an anabolic steroid on mRNA expression of a muscle growth factor, insulin-like growth factor-I autocrine variant, or mechano-growth factor (MGF). METHODS: Twelve 8-week-old male Wistar rats were used. Metenolone was administered and passive repetitive dorsiflexion and plantar flexion of the ankle joint performed under deep anesthesia. After 24 h, the gastrocnemius muscles were removed and the mRNA expression of insulin-like growth factor-I autocrine variant was measured using quantitative real-time polymerase chain reaction. RESULTS: Repetitive stretching in combination with metenolone, but not stretching alone, significantly increased MGF mRNA expression. CONCLUSION: Anabolic steroids enhance the effect of passive stretching on MGF expression in skeletal muscle.

Passive repetitive stretching for a short duration within a week increases myogenic regulatory factors and myosin heavy chain mRNA in rats' skeletal muscles.

Stretching is a stimulation of muscle growth. Stretching for hours or days has an effect on muscle hypertrophy. However, differences of continuous stretching and repetitive stretching to affect muscle growth are not well known. To clarify the difference of continuous and repetitive stretching within a short duration, we investigated the gene expression of muscle-related genes on stretched skeletal muscles. We used 8-week-old male Wistar rats (N = 28) for this study. Animals medial gastrocnemius muscle was stretched continuously or repetitively for 15 min daily and 4 times/week under anesthesia. After stretching, muscles were removed and total RNA was extracted. Then, reverse transcriptional quantitative real-time PCR was done to evaluate the mRNA expression of MyoD, myogenin, and embryonic myosin heavy chain (MyHC). Muscles, either stretched continuously or repetitively, increased mRNA expression of MyoD, myogenin, and embryonic MyHC more than unstretched muscles. Notably, repetitive stretching resulted in more substantial effects on embryonic MyHC gene expression than continuous stretching. In conclusion, passive stretching for a short duration within a week is effective in increasing myogenic factor expression, and repetitive stretching had more effects than continuous stretching for skeletal muscle on muscle growth. These findings are applicable in clinical muscle-strengthening therapy.

Quantitative behavioral evaluation of a non-human primate stroke model using a new monitoring system.

Background: Recently, the common marmoset (Callithrix jacchus) has attracted significant interest as a non-human primate stroke model. Functional impairment in non-human primate stroke models should be evaluated quantitatively and successively after stroke, but conventional observational assessments of behavior cannot fully fit this purpose. In this paper, we report a behavioral analysis using MarmoDetector, a three-dimensional motion analysis, in an ischemic stroke model using photosensitive dye, along with an observational behavioral assessment and imaging examination. Methods: Ischemic stroke was induced in the left hemisphere of three marmosets. Cerebral infarction was induced by intravenous injection of rose bengal and irradiation with green light. The following day, the success of the procedure was confirmed by magnetic resonance imaging (MRI). The distance traveled, speed, activity time, and jumps/climbs were observed for 28 days after stroke using MarmoDetector. We also assessed the marmosets' specific movements and postural abnormalities using conventional neurological scores. Results: Magnetic resonance imaging diffusion-weighted and T2-weighted images showed hyperintense signals, indicating cerebral infarction in all three marmosets. MarmoDetector data showed that the both indices immediately after stroke onset and gradually improved over weeks. Neurological scores were the worst immediately after stroke and did not recover to pre-infarction levels during the observation period (28 days). A significant correlation was observed between MarmoDetector data and conventional neurological scores. Conclusion: In this study, we showed that MarmoDetector can quantitatively evaluate behavioral changes in the acute to subacute phases stroke models. This technique can be practical for research on the pathophysiology of ischemic stroke and for the development of new therapeutic methods.

Exercise enhanced functional recovery and expression of GDNF after photochemically induced cerebral infarction in the rat.

Exercise has been considered to affect the functional recovery from central nervous damage. Neurotrophic factors have various effects on brain damage. However, the effects of exercise for expression of GDNF on functional recovery with brain damage are not well known. We investigated the difference in functional recovery between non-exercise and beam-walking exercise groups, and the expression of GDNF in both groups after photochemical infarction. Adult male Wistar rats (N = 64) were used. Animals were divided into two groups: non-exercise (N = 35), and beam-walking exercise (N = 29). All rats underwent surgical photochemical infarction. The rats of the beam-walking group were trained every day to walk on a narrow beam after a one-day recovery period and those of the non-exercise group were left to follow a natural course. Animals were evaluated for hind limb function every day using a beam-walking task with an elevated narrow beam. The number of GDNF-like immunoreactive cells in the temporal cortex surrounding the lesion was counted 1, 3, 5, and 7 days after the infarction. Functional recovery of the beam-walking exercise group was significantly earlier than that of the non-exercise group. At 3 days after infarction, the number of GDNF-positive cells in the temporal cortex surrounding the infarction was significantly increased in the beam-walking exercise group compared with that in the non-exercise group. In the exercise group, motor function was remarkably recovered with the increased expression of GDNF-like immunoreactive cells. Our results suggested that a rehabilitative approach increased the expression of GDNF and facilitated functional recovery from cerebral infarction.

Contralateral cortical role on functional recovery in a rat model of hemiplegia.

The role of the contralateral cerebral cortical plasticity in functional recovery after cerebral infarction is controversial. To clarify this role, we made a second contralateral cortical infarction after recovery from the first cerebral infarction. To produce the first infarction, Wistar rats were intravenously injected with Rose Bengal to the sensorimotor area of the right hemisphere of the cerebral cortex under green-light irradiation. Two weeks after the first hemiplegia, a secondary infarction was induced in the left cerebral cortex. Functional recovery was evaluated in a beam-walking test. Hemiplegia observed 1 day after both the first and second infarctions was given a score of 1. At 14 days after the first infarction, the average recovery score (± standard error) was 6.8 ± 0.1. In contrast, functional recovery was slower after the second infarction, reaching an average score of only 3.5 ± 0.5 after 14 days. Therefore, recovery after the contralateral secondary infarction was slower than that from the first, and received a lower recovery score compared to the recovery after the first infarction. These results suggest that the undamaged contralateral cortex plays an important role in motor recovery after hemiplegia caused by cerebral infarction.

Expected for acquisition movement exercise is more effective for functional recovery than simple exercise in a rat model of hemiplegia.

BACKGROUND AND PURPOSE: The use of novel rehabilitative approaches for effecting functional recovery following stroke is controversial. Effects of different but effective rehabilitative interventions in the hemiplegic patient are not clear. We studied the effects of different rehabilitative approaches on functional recovery in the rat photochecmical cerebral infarction model. METHODS: Twenty-four male Wistar rats aged 8 weeks were used. The cranial bone was exposed under deep anesthesia. Rose bengal (20 mg/kg) was injected intravenously, and the sensorimotor area of the cerebral cortex was irradiated transcranially for 20 min with a light beam of 533-nm wavelength. Animals were divided into 3 groups. In the simple-exercise group, treadmill exercise was performed for 20 min every day. In the expected for acquisition movement-training group, beam-walking exercise was done for 20 min daily. The control group was left to recover without additional intervention. Hindlimb function was evaluated with the beam-walking test. RESULTS: Following cerebral infarction, dysfunction of the contralateral extremities was observed. Functional recovery was observed earlier in the expected for acquisition training group than in the other groups. Although rats in the treadmill group recovered more quickly than controls, the beam-walking group had the shortest overall recovery time. CONCLUSIONS: Exercise facilitated functional recovery in the rat hemiplegic model, and expected for acquisition exercise was more effective than simple exercise. These findings are considered to have important implications for the future development of clinical rehabilitation programs.

A new non-human primate model of photochemically induced cerebral infarction.

BACKGROUND AND PURPOSE: Rat models of photochemically induced cerebral infarction have been readily studied, but to date there are no reports of transcranial photochemically induced infarctions in the marmoset. In this report, we used this non-human primate as a model of cerebral thrombosis and observed the recovery process. METHODS: Five common marmosets were used. Cerebral ischemia was produced via intravascular thrombosis induced by an intravenous injection of Rose Bengal and irradiation with green light. After inducing cerebral infarction, we observed the behavior of marmosets via a continuous video recording. We evaluated maximum speed, mean speed, and distance traveled in 1 min. In addition, we evaluated scores for feeding behavior, upper limb grip, and lower limb grip. We confirmed the infarct area after cerebral infarction using 2,3,5-triphenyltetrazolium chloride staining in a separate marmoset. RESULTS: We found functional decreases 2 days after creating the cerebral infarction in all measurements. Total distance traveled, average speed, upper limb score, and feeding behavior score did not recover to pre-infarction levels within 28 days. Maximum speed in 1 min and lower limb score recovered 28 days after infarction as compared to pre-infarction levels. We confirmed the infarct area of 11.4 mm × 6.8 mm as stained with 2,3,5-triphenyltetrazolium chloride. CONCLUSION: We were able to create a primate photothrombosis-induced cerebral infarction model using marmosets and observe functional recovery. We suggest that this is a useful model for basic research of cerebral infarction.

Effect of menthol on detrusor smooth-muscle contraction and the micturition reflex in rats.

OBJECTIVES: To investigate the effects of menthol, an activator of the temperature-sensitive transient receptor potential family member TRPM8, on detrusor smooth-muscle contraction and the micturition reflex in rats. METHODS: We evaluated the effect of intravesical infusion of 1 or 3 mM menthol by cystometry in conscious female Sprague-Dawley rats. Some of the animals were pretreated with 125 mg/kg capsaicin subcutaneously 4 days earlier. The parameters measured were voided volume (VV), residual volume (RV), volume threshold for inducing micturition (VT), voiding efficiency (VE), micturition pressure (MP), and pressure threshold for inducing micturition (PT). Strips of detrusor muscle were mounted in organ baths to study the effect of menthol on the contractile response to 0.01 mM carbachol. RESULTS: Intravesical infusion of 3 mM menthol reduced VV by 20%, VT by 19%, and PT by 31%. RV, VE, and MP were unaltered. Capsaicin pretreatment had no effect on baseline cystometric parameters, and 3 mM menthol caused similar reductions in VV (24%), VT (22%), and PT (30%), while having no effect on RV, VE, and MP. Menthol at 0.1, 0.3, and 1 mM inhibited carbachol-induced contractions by 10.7%, 36.7%, and 97.3%, respectively. CONCLUSIONS: Our results demonstrated that intravesical infusion of menthol facilitated the micturition reflex, and capsaicin pretreatment had no effect on this response. Menthol inhibited carbachol-induced contraction of the detrusor smooth muscle. This suggests that intravesically infused menthol cannot relax detrusor muscle, and acts on capsaicin-resistant afferents (probably through TRPM8 in urothelium or sensory nerve endings) to facilitate the micturition reflex.

Functional recovery and expression of GDNF seen in photochemically induced cerebral infarction.

Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor involved in the survival and proliferation of neurons. However, there have been few reports examining the relationship between GDNF and functional recovery after cerebral infarction. The authors investigated the change in the expression of GDNF proteins during functional recovery in rats following photochemically induced cerebral infarctions. Functional recovery for the first 14 days after the infarction was evaluated using a beam-walking test. The number of GDNF-like immunoreactive cells around the infarction were counted at various times (24 h, 72 h, 7 days, and 14 days) post-infarction. Immunohistochemical analysis of brain sections showed that the expression of GDNF-like immunoreactive cells was significantly increased in the temporal cortex until 7 days on the side ipsilateral to the infarction, and had decreased by 14 days. Likewise, the functional recovery of paralysis was substantial until 7 days post-infarction, after which the improvement was mild. Therefore, the expression of GDNF protein might have some relationship with the functional recovery of paralysis. There are great hopes that GDNF could be used as a therapeutic agent for cerebral infarction.

Combination effect of AC-7700, a novel combretastatin A-4 derivative, and cisplatin against murine and human tumors in vivo.

The in vivo combination effect of AC-7700, a novel combretastatin A-4 derivative, and cisplatin (CDDP) was examined. The combination of AC-7700 and CDDP increased antitumor activity against murine colon 26 tumor in mice and cured the mice. This combination effect was found over wide dosage ranges of AC-7700 (20-80 mg/kg) and CDDP (2.5-5 mg/kg). Moreover, this combination augmented antitumor activity against murine S180 and M109 tumors, and human LX-1 and LS180 tumor xenografts in mice. The effect was the strongest when AC-7700 and CDDP were administered simultaneously. To study this combination effect, we measured the concentrations of CDDP in tumors, plasma and kidneys of the mice with colon 26 tumor. In the combination with AC-7700, the concentration of CDDP in the tumors increased from 0.5 to 96 h after administration, but did not change or decrease in plasma or kidneys. Against human LS180 xenografts in mice, the combination similarly increased the concentration of CDDP in the tumors. These results suggest that AC-7700 may specifically augment the accumulation of CDDP in tumors, and thus has the potential to be useful in combination chemotherapy with CDDP.