Acupuncture Point "Hegu" (LI4) Is Close to the Vascular Branch from the Superficial Branch of the Radial Nerve.

The acupuncture point "Hegu" (LI4) has been used for treating peripheral circulatory failure, which is located in the area covered by the superficial branch of the radial nerve (SBRN). SBRN has branches reaching arteries, so-called vascular branches (VBs), which are thought to be involved in the arterial constriction. The distribution areas of the VBs from the SBRN have been reported, but the positional relationship between these distribution areas and the acupuncture points are not known. To examine the positional relationship between LI4 and VBs from the SBRN, forty hands were examined to assess the positional relationship between the acupuncture points "Erjian" (LI2), "Sanjian" (LI3), LI4, and "Yangxi" (LI5) in the Yangming Large Intestine Meridian of Hand, which are located in the area covered by SBRN, and the VBs from the SBRN. After the VBs were identified, the distances from the acupuncture points (LI2, LI3, LI4, and LI5) to the point where the VBs reached the radial artery or the first dorsal metacarpal artery were measured. VBs reaching the radial arteries were observed in all specimens. The mean distances from LI2, LI3, LI4, and LI5 to the point where the VBs reached the radial artery were 64.2 ± 8.2 mm, 42.0 ± 7.5 mm, 4.3 ± 4.3 mm, and 33.0 ± 4.8 mm, respectively. LI4 was significantly closer than the other acupuncture points (P<0.01). The nerve fibers of the VBs adjacent to the radial artery were confirmed using hematoxylin and eosin staining. Our findings provide anatomical evidence that stimulation at LI4 is used for treating peripheral circulatory failure such as Raynaud's disease. LI4 is significant because it is located at a source point, making it clinically important.

Manserin, a secretogranin II-derived peptide, distributes in the rat endocrine pancreas colocalized with islet-cell specific manner.

Manserin is a recently characterized 40-amino acid neuropeptide derived from secretogranin II, a protein belonging to the chromogranin family. Although the physiological roles of manserin have not been elucidated to date, manserin has been shown to distribute in not only the brain but also the endocrine system such as the pituitary and adrenal glands, suggesting its role in the endocrine system. The present study aimed to explore the occurrence and distribution of manserin in the rat pancreas using an immunohistochemical technique with a polyclonal antibody against rat manserin. Immunoreactivity for manserin was readily detected in almost whole islets of Langerhans whereas not at all in the exocrine pancreas. Manserin-expressing cells were not colocalized with the glucagon-secreting cells (alpha cells), whereas they colocalized with insulin-secreting cells (beta cells) and somatostatin-secreting cells (delta cells), although their intracellular distribution was different. These results indicate that manserin, occurring in the endocrine pancreas, may have a potential role in the endocrine system.

Nonexploratory movement and behavioral alterations in a thalidomide or valproic acid-induced autism model rat.

Autism is a behaviorally characterized disorder with impairments in social interactions, as well as stereotyped, repetitive patterns of behaviors and interests. Exposure of rat fetuses to thalidomide (THAL) or valproic acid (VPA) on the ninth day of gestation has been reported as a useful model for human autism. We have shown that early serotonergic neural development is disrupted in these rats. In the current study, we used a radial maze and open field experimental paradigm to investigate whether these rats present behavioral and/or learning aberrations. THAL (500mg/kg), VPA (800mg/kg), or vehicle was administered orally to E9 pregnant rats at 7-10 weeks of age. Although the mean number of correct and incorrect arm choices in the initial eight arm choices did not differ between control and teratogen-exposed groups, achievement of learning (seven or eight consecutive correct choices for 3 consecutive days for individual rats) seemed to be impaired in teratogen-exposed groups. Interestingly, average time to explore the maze task was shorter in the teratogen-exposed groups, indicating that correct choice might be due to mere coincidence (i.e., nonexploratory movement). Unexpectedly, no significant differences were observed in social interaction in these rats. These results indicate that prenatal exposure to THAL and VPA might alter behavior in a manner that is, in part, consistent with human autism.

Hypoxia-induced astrocytes promote the migration of neural progenitor cells via vascular endothelial factor, stem cell factor, stromal-derived factor-1alpha and monocyte chemoattractant protein-1 upregulation in vitro.

1. The aim of the present study was to examine if and how rat hypoxia-induced astrocytes affect the migration of neural progenitor cells (NPC) and to investigate the expression patterns of some chemokines, such as vascular endothelial growth factor (VEGF), stem cell factor (SCF), stromal-derived factor-1alpha (SDF-1alpha), fractalkine and monocyte chemoattractant protein-1 (MCP-1) in hypoxia-induced astrocytes and their contribution to NPC migration in vitro. 2. Costar Transwell inserts were used for the chemotaxis assay and quantified changes in the chemokines mRNA for between 0 h and 24 h posthypoxia were tested using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. The results showed that the chemotaxis of astrocyte cells exposed to hypoxia for 18 h reached a peak value, whereas the chemotaxis of astrocytes exposed to hypoxia for 24 h began to decrease compared with those exposed to hypoxia for 18 h. Hypoxia upregulated chemokine VEGF, SCF, SDF-1alpha and MCP-1 expression in a time-dependent manner but downregulated fractalkine expression in astrocytes. In addition, the time points of the peak expressions for VEGF, SCF, SDF-1alpha and MCP-1 were similar to the time point of maximum NPC migration. 3. Specific inhibitors that block the binding of specific chemokines to its receptors were used for analysing the contribution of the chemokine to NPC migration. When VEGF, SCF, SDF-1alpha and MCP-1 were each inhibited independently, NPC migration was reduced. When they were inhibited together, NPC migration was obviously inhibited compared with both the control and single-block cultures, which implies that the migratory effect of hypoxia-induced astrocytes was synergetic by several chemokines. 4. In conclusion, we demonstrated the time-dependent manner of NPC migration promotion by hypoxia-induced astrocytes. We also provide evidence that soluble factors, such as VEGF, SCF, SDF-1alpha and MCP-1, released from astrocytes, direct the migration of NPC under hypoxic circumstances. Given that astrocytes were activated to all hypoxia-ischaemia diseases, these results indicate an important role for astrocytes in directing NPC replacement therapy in the central nervous system.

Split dose recovery studies using homologous recombination deficient gene knockout chicken B lymphocyte cells.

To understand the role of proteins involved in DSB repair modulating SLD recovery, chicken B lymphoma (DT 40) cell lines either proficient or deficient in RAD52, XRCC2, XRCC3, RAD51C and RAD51D were subjected to fractionated irradiation and their survival curves charted. Survival curves of both WT DT40 and RAD52 (-/-) cells had a big shoulder while all the other cells exhibited small shoulders. However, at the higher doses of radiation, RAD51C(-/-) cells displayed hypersensitivity comparable to the data obtained for the homologous recombination deficient RAD54(-/-) cells. Repair of SLD was measured as an increase in survival after a split dose irradiation with an interval of incubation between the radiation doses. All the cell lines (parental DT40 and genetic knockout cell lines viz., RAD52(-/-), XRCC2(-/-), XRCC3(-/-) RAD51C(-/-) and RAD51D(-/-)) used in this study demonstrated a typical split-dose recovery capacity with a specific peak, which varied depending on the cell type. The maximum survival of WT DT40 and RAD52(-/-) was reached at about 1-2 hours after the first dose of radiation and then decreased to a minimum thereafter (5h). The increase in the survival peaked once again by about 8 hours. The survival trends observed in XRCC2 (-/-), XRCC3(-/-), RAD51C (-/-) and RAD51D(-/-) knockout cells were also similar, except for the difference in the initial delay of a peak survival for RAD51D(-/-) and lower survival ratios. The second phase of increase in the survival in these cell lines was much slower in XRCC2(-/-) , XRCC3(-/-), RAD51C(-/-) and RAD51D(-/-) and further delayed when compared with that of RAD52(-/-) and parental DT40 cells suggesting a dependence on their cell cycle kinetics. This study demonstrates that the participation of RAD52, XRCC2, XRCC3, RAD51C and RAD51D in the DSB repair via homologous recombination is of less importance in comparison to RAD54, as RAD54 deficient cells demonstrated complete absence of SLD recovery.

Positron emission tomography analysis of the analgesic effects of acupuncture in rhesus monkeys.

The purpose of this study was to examine whether pain-induced brain activation was suppressed by acupuncture analgesia. We investigated the suppression of the pain-induced neuronal activation in specific brain areas of three male rhesus monkeys (aged four years old) using positron emission tomography (PET), in which changes in the regional cerebral blood flow (rCBF) were examined as an index of the neuronal activation. The brain areas such as the thalamus, insula and anterior cingulate cortex were activated by heating the tail of monkeys in 47 degrees C water compared to the heating at 37 degrees C. Those activations were suppressed by electroacupuncture (EA) with a 2 sec alteration of the frequency of 4 Hz/60 Hz at the right ST36 (the upper anterior tibial muscle) and the right LI4 (the back palm between the first and second metacarpal) acupoints. Meanwhile, this EA analgesic effect was confirmed by prolonging the tail withdrawal latencies from hot water in the temperature range from 45 to 50 degrees C.These brain areas were corresponded to the pain-related areas as reported in previous studies. In conclusion, we were able to visualize the acupuncture analgesia in the CNS. We also detected the brain areas activated or inactivated by acupuncture. The areas that responded to acupuncture stimulation at 47 degrees C water were different from the regions at 37 degrees C. We consider that this difference in the response to acupuncture may support the variation of the clinical efficacy of acupuncture in patients bearing pain or other disorders.

Effects of Chinese herbal medicine based on hachimi-jio-gan on osteopenia in rats.

The effects of Chinese herbal medicines including Hachimi-jio-gan (HJG) and/or Hochu-ekki-to (HEW) on osteopenia in rats were investigated. The Chinese herbal medicines were administrated for 8 weeks (7 times/week) starting from 1 week after ovariectomy. HJG and Prescription-2 (Prsc-2, the prescription based on HJG) showed protective effect on bone loss of the vertebrae after ovariectomy. However, Prescription-1 (the prescription based on HJG and HET) had no effect. Then, we made osteopenia model in rats by prednisolone and low calcium diet. Prsc-2 and HJG were administrated for 20 weeks with prednisolone. These Chinese remedies showed protective effects for osteopenia, with better indices on bone loss of the limbs than HJG alone in the osteopenia rats. It can be concluded that Prsc-2 is more effective than HJG for bone loss induced by various factors, and the additives in Prsc-2 may enhance the therapeutic effect.

Sex difference of adenine effects in rats: renal function, bone mineral density and sex steroidogenesis.

Adenine is widely used in clinical field, however, an excess of adenine is harmful. It is known that the feeding of an adenine-rich diet induces renal failure and decreases bone mineral density (BMD) and the serum testosterone level in male rats. However, there is little information about the influence of adenine on female animals. We compared the effects of adenine treatment between male and female rats. Young male and female rats were administered adenine adjusted with distilled water (6 mg/ml, 50 mg/ml and 100 mg/ml) for 8 weeks (3 times/week, 8-16 week old). In male rats, renal failure was induced by 100 mg/ml adenine treatment and renal dysfunction was induced by 50 mg/ml adenine treatment. Bone loss and the reduction of the testosterone level were also caused by both concentrations of adenine. However, the serum testosterone level and BMD in male rats were decreased by 6 mg/ml adenine treatment by which renal dysfunction was not caused. It is suggested that adenine directly affected bone metabolism and sex steroidgenesis in male animals, not through altering renal dysfunction. In female rats, conversely, renal dysfunction was induced only in the 100 mg/ml group, which was somewhat different from the observation in male rats. The serum 17-beta estradiol level and the BMD in female rats were not affected by adenine treatment at all. In conclusion, there is a significant difference of the effects of adenine, which is commonly contained in medicine and general foods, on steroidgenesis and renal function between male and female rats.

Effects of the Chinese herbal medicine based on Hachimi-jio-gan in male rats with the adenine-induced osteopenia.

In the adenine-induced renal failure rats, reversibility of renal failure and recovery of bone mineral density (BMD) by discontinuation of adenine-rich diet were reported. We think that the effect to bone metabolism with medication may be able to be evaluated as reinforcement of the BMD recovery. We have so far investigated the Chinese herbal medicine based on Hachimi-jio-gan (HJG) which are more effective than HJG alone. In this study, we investigated the effects of our Chinese herbal prescription on BMD in the adenine-treated rats compared to that of vitamin D3 treatment. Young male rats were administrated 100 mg/ml adenine for 8 weeks, and they showed renal failure and bone loss. The adenine-treated rats were divided into the following 3 groups, that is, the group experienced no treatment (control), the group given our Chinese herbal medicine (HAO), and the group given vitamin D3 (VD3) medication. It is likely that VD3 medication was less effective for increase of the femoral BMD than increase of the spinal BMD. In contrast, HAO was effective for increase of the femoral BMD. The VD3 group showed low deoxypyridinoline (Dpd: bone resorption maker) as compared to the control group. However, the HAO group showed same or slightly high Dpd. It is suggested that VD3 may increase BMD by reduction of bone resorption, while HAO may show effect on BMD by activating bone metabolism. It is indicated that HAO may become a curative medicine for bone loss because of the different target site from vitamin D3.