Efficacy of sucroferric oxyhydroxide treatment in Japanese hemodialysis patients and its effect on gastrointestinal symptoms.

Sucroferric oxyhydroxide (SFOH) is a non-calcium, iron-based phosphate binder indicated for the treatment of hyperphosphatemia in adult dialysis patients. Studies in Japan about the side effects of SFOH treatment indicate that the incidence of diarrhea (25%) is greater while that of constipation (2.9%) is lesser in comparison to that observed upon treatment with an existing phosphate binder. In the present study, the effect of treatment with a combination of the existing phosphate binders and SFOH on the serum phosphorus level and digestive symptoms was observed in hemodialysis patients with hyperphosphatemia, which is untreatable using only the existing phosphate binders. We evaluated the serum phosphorus levels and gastrointestinal symptoms (using the gastrointestinal symptom rating scale) of 6 patients (2 men, 4 women) before and 2, 4, 6, and 8 weeks after continuous administration. The serum phosphorus levels before and 2, 4, 6, and 8 weeks after combination treatment were 7.4±1.0 mg/dL, 5.9±1.3 mg/dL, 5.8±1.5 mg/dL, 5.8±1.4 mg/dL, and 5.8±1.3 mg/dL, respectively, with significant reduction in the levels being observed 2 weeks after administration (p<0.05) and persisting even 8 weeks after continuous administration. The constipation scores before and 2, 4, and 8 weeks after drug administration were 2.39±0.85, 2.34±1.93, 2.56±1.44, and 3.28±2.19, respectively, with no changes observed during the investigation period. The diarrhea scores before and 2, 4, and 8 weeks after drug administration were 2.22±0.91, 2.06±1.16, 1.28±0.39, and 1.06±0.13 respectively. The scores improved significantly, 4 weeks after drug administration (p<0.05), and the improvement persisted, even 8 weeks after continuous administration. Thus, by using a combination of the existing phosphate binders and SFOH, we were able to reduce the serum phosphorus level in patients with hyperphosphatemia, which is untreatable using the existing phosphate binder alone, with no sign of exacerbation of the gastrointestinal symptoms despite a few contradictory case reports.

Intrapartum care at a tertiary hospital in Cambodia: a survey using the Bologna Score.

BACKGROUND: developing countries strive to reduce maternal- and child mortality, partly through establishing health centres/hospitals with skilled birth attendants. The aim of this study was to describe childbirth care, by the use of the Bologna Score at a tertiary hospital in Cambodia with approximately 8,500 births per year. METHODS: a prospective cross-sectional study. The Bologna Score instrument, which reflects the adaption of evidence-based care and attitudes of caregivers, was used for data collection and three study specific questions. The midwives collected data from 177 consecutive childbirths. RESULTS: all women were assisted by a skilled birth attendant, the majority by a midwife (63%) and the remaining women by a physician (35%) or midwife student under supervision. A spontaneous vaginal birth was planned for 82% of the women. All women seeking care at the hospital survived the childbirth. A full 5-point Bologna Score, suggesting evidence-based management for women with spontaneous vaginal birth, was not achieved for any of the women. The use of supine position and lack of an accompanying person in the birth room, were items responsible for loss of points. Partogram and skin-to-skin contact between baby and mother were items noted for three quarters of the planned vaginal births, and the item 'Absence of labour augmentation', was affirmed to a great extent. Little more than half of the women had an episiotomy and almost 16% of the children had an Apgar score <7 at 5 mins. CONCLUSION: the Bologna Score was easy to use and pointed at items that could be improved. It was satisfying that all women survived, but alarming that 16% of the children had a low Apgar score. The findings suggest that childbirth care can be improved at the hospital.

Aconiti tuber (Bushi) improves microcirculatory disturbances induced by endotoxin in rats.

The present study investigated the effects of processed Aconiti tuber (TJ-3022, Tsumura-shuchi-bushi), a traditional herbal medicine (Kampo), on microcirculatory disturbances induced by endotoxin in the rat mesentery. The changes in arteriolar diameter, the velocity of red blood cells in arterioles and the venular microcirculation after endotoxin injection (6 mg/kg, iv) were observed using videomicroscopy. The mean arterial pressure and heart rate were monitored continuously during the experiments. TJ-3022 prevented significantly the decrease of mean arterial pressure, controlled the reduced velocity and apparently also inhibited leukocyte extravasation across venules. However, there were no significant changes in the arteriolar diameter and the heart rate between the groups treated with and without TJ-3022. The results indicate that processed Aconiti tuber (TJ-3022) has protective effects in improving microcirculatory disturbances induced by endotoxin in rat mesentery.

Suppressive effects of Neiting acupuncture on toothache: an experimental analysis on Fos expression evoked by tooth pulp stimulation in the trigeminal subnucleus pars caudalis and the periaqueductal gray of rats.

To clarify the antinociceptive mechanism of acupuncture on acute pain, c-fos protein (Fos) expression induced by tooth pulp stimulation was immunohistochemically examined in the spinal trigeminal subnucleus pars caudalis (spVc) and the periaqueductal gray (PAG) of rats with or without Neiting acupuncture. The central projection of trigeminal ganglion neurons innervating in the tooth pulp was examined by tract-tracing method with horseradish peroxidase-conjugated wheat germ agglutinin (WGA-HRP). Central terminals from the first maxillary molar tooth were labeled transganglionically in the dorsomedial part of spVc with WGA-HRP. Numerous numbers of Fos-immunoreactive (Fos-ir) cells were found in the spVc and PAG by stimulation of the tooth pulp with acetic acid or saline. Neiting acupuncture significantly reduced the Fos expression in the spVc induced by tooth pulp stimulation. On the other hand, Neiting acupuncture evoked many Fos-ir cells in the PAG. The present results suggest that Neiting acupuncture activated PAG neurons that sent descending inhibitory fibers to medullo-spinal nociceptive neurons, and reduced the number of Fos-expressed neurons in the trigeminal subnucleus pars caudalis mediating noxious information from teeth to the higher central nervous system.

Sinitang (Shigyaku-to), a traditional Chinese medicine improves microcirculatory disturbances induced by endotoxin in rats.

The present study investigated the effects of Sinitang (Japanese name: Shigyaku-to--a traditional Chinese medicine), on microcirculatory disturbances induced by endotoxin in rat mesentery. The changes of arteriolar diameter, the velocity of red blood cells in arterioles and venular microcirculation after endotoxin injection (6 mg x kg(-1), i.v.) were observed by videomicroscopy. Mean arterial pressure and heart rate were monitored continuously during the experiments. Sinitang significantly prevented the decrease of mean arterial pressure, controlled the reduced velocity and also, apparently inhibited the leukocyte extravasation across venules. However, there were no significant changes in the arteriolar diameter and the heart rate in all groups treated with or without Sinitang. The results indicate that Sinitang has protective effects to improve the microcirculatory disturbances induced by endotoxin in rat mesentery.

The herbal medicine, sairei-to, enhances the mucociliary activity of the tubotympanum in the healthy guinea pig.

Mucociliary dysfunction in the tubotympanum is deeply reflected in the clinical manifestations of otitis media with effusion (OME), and clinical application of pharmacological agents with ciliostimulatory action might therefore enhance the mucociliary clearance function of the tubotympanum to more effectively eliminate middle ear effusions to the pharynx. A herbal medicine, sairei-to, enhances the in vitro ciliary activity of the middle ear during culture. However, this ciliostimulatory effect is not always applicable to the mucociliary system in situ, which may be deteriorated following oral administration of sairei-to. The present study therefore aimed at investigating the in vivo effect of sairei-to on the mucociliary system in the tubotympanum of the guinea pig. Thirty healthy guinea pigs were used. Ten animals were treated with oral administration of physiologic saline solution for 14 successive days. The remaining animals were treated with oral administration of 120 or 600 mg/kg body weight of sairei-to for 14 successive days. Each animal was used for examination of the ciliary activity and mucociliary clearance time of the tubotympanum, 24 h after the final treatment. No significant changes in either ciliary activity or mucociliary clearance time of the tubotympanum were observed upon administration of 120 mg/kg of sairei-to, which was equivalent to the clinical human dosage. By contrast, oral administration of 600 mg/kg of sairei-to significantly enhanced the ciliary activity, but failed to significantly accelerate mucociliary clearance in the tubotympanum, although the mean value of the clearance time became shorter. Therefore, our results suggest that sairei-to to some extent stimulates the function of the mucociliary system. In conclusion, the herbal medicine, sairei-to, might be useful in the treatment of OME, and preventive administration of this drug may be a new therapy in the treatment of recurrent OME.

The herbal medicine, sairei-to, prevents endotoxin-induced otitis media with effusion in the guinea pig.

With current pharmacotherapy, otitis media with effusion (OME) is often recurrent and even develops to become chronic. There is now considerable experimental and clinical evidence that the cilia in the tubotympanum play an important part in the prevention of OME. A herbal medicine, sairei-to, has been shown to stimulate the ciliary activity in vitro, and oral administration of the medicine also stimulated the ciliary activity in the tubotympanum rather than physiological states. This study was designed to investigate whether oral administration of sairei-to could prevent experimental OME in the guinea pig. A total of 120 guinea pigs were used. The control group was treated with intratympanic injection of 0.1 ml of physiologic saline solution. The saline-control group was treated with oral administration of physiologic saline solution for 14 successive days. The low-dosage group and the high-dosage group were treated with oral administration of 120 and 600 mg/kg of sairei-to for 14 successive days, respectively. The saline-control group, the low-dosage group and the high-dosage group were then treated with intratympanic injection of 0.1 ml of lipopolysaccharide solution (100 micrograms/ml) derived from Klebsiella pneumoniae. All 10 animals from the 4 groups were sacrificed 1, 3, and 7 days after the intratympanic injection, to examine ciliary activity, mucociliary clearance time, and mucosal pathology of the tubotympanum. The saline-control group exhibited middle ear effusions and pathologies similar to human OME. The incidence of middle ear effusions in the low-dosage and the high-dosage groups was somewhat reduced compared with the saline-control group. The ciliary activity in the tubotympanum was significantly reduced in the saline-control and low-dosage groups compared with the normal-control group. By contrast, the magnitude of reduction in ciliary activity was much smaller in the high-dosage group. The ciliary activity especially in the Eustachian tube and the middle ear close to the tympanic orifice at 3 and 7 days in the high-dosage group was not significantly different from that in the normal-control group. Mucociliary clearance time in the high-dosage group was not different from that in the normal-control group throughout the observation period. The groups treated with sairei-to, especially the high-dosage group, exhibited much milder pathological changes in the tubotympanum than did the saline-control group. In conclusion, clinical application of sairei-to could be an effective measure to prevent the occurrence of OME and also the recurrence of the disease, especially OME-prone individuals.

Effects of Chinese herbal medicines on DNA-synthesizing enzyme activities in mammary tumors of mice.

Sho-saiko-to (SST) and Juzen-taiho-to (JTT), Japanese modified Chinese herbal prescriptions, suppressed the activities of thymidylate synthetase and thymidine kinase involved in de novo and salvage pathways for pyrimidine nucleotide synthesis, respectively, in mammary tumors of SHN mice with the reduction of serum prolactin level. These results indicate that SST and JTT may have the antitumor effects on mammary tumors.

Suppression by kampo medicines in preneoplastic mammary hyperplastic alveolar nodules of SHN virgin mice.

Sho-saiko-to (SST), Keishi-bukuryo-gan (KBG), and Shakuyaku-kanzo-to (SKT) are Japanese modified traditional Chinese herbal medicines (Kampo medicines) consisting of 7, 5, and 2 medical plants, respectively. It is known that the hyperplastic alveolar nodule (HAN) is a representative preneoplastic state in the mammary glands of mice. We examined the effects of SST, KBG, and SKT on the formation and growth of HAN in a high-mammary-tumor strain of SHN virgin mice. Oral administration of SST for 60 days beginning at 90 days of age reduced the number and area of HAN and mammary thymidylate synthetase activity with a reduction of serum prolactin level. There was little difference between the other experimental groups and the control in the formation and growth of HAN and the enzyme activities. These results indicate that SST may have a preventive effect on malignant mammary transformations.

Effects of kampo (Japanese herbal) medicine "sho-saiko-to" on DNA-synthesizing enzyme activity in 1,2-dimethylhydrazine-induced colonic carcinomas in rats.

Sho-Saiko-To (SST) is a modified Japanese traditional Chinese herbal medicine containing seven medical plants: Bupleuri radix, Pinelliae tuber, Suxtallariae radix, Zizyphi fructus, Ginseng radix, Glycyrrhizae radix, and Zingiberis recens rhizoma. This preparation has been used in the treatment of some inflammatory diseases of the respiratory system and chronic hepatitis. In the present study, the effects of SST were investigated on the activities of DNA-synthesizing enzymes in 1,2-dimethylhydrazine (DMH)-induced colonic carcinomas in rats. Six-week administration of SST prevented nearly 100% of the body weight loss and the final number of the colonic carcinomas compared to those in the rats treated with DMH alone, and suppressed the enhanced activities of thymidylate synthetase (TS) and thymidine kinase (TK) which were involved in the de novo and salvage pathways of pyrimidine synthesis, respectively, in DMH-induced colonic carcinomas. These results indicate that SST may show directly and/or indirectly inhibitory effects on the development of colonic carcinomas.

Use of monoclonal antibodies, enzyme-linked immunosorbent assay and immunoaffinity column chromatography to determine ochratoxin A in porcine sera, coffee products and toxin-producing fungi.

Ochratoxin A, produced by a number of fungal species, has been found in many milieu, including porcine sera and coffee beans. It was therefore analysed by enzyme-linked immunosorbent assay (ELISA) in porcine sera, coffee products and fungal cultures, using monoclonal antibodies, a monoclonal antibody-linked immunoaffinity column (IAC) and high-performance liquid chromatography (HPLC). The chloroform extracts of acidified porcine sera were assayed directly by ELISA, with alkaline phosphatase and horseradish peroxidase as marker enzymes, at detection limits of 0.1 and 0.01 ng/ml, respectively. The presence of ochratoxin A in ELISA was confirmed by HPLC. The average contents in the five different lots tested were: 0.4 ng/ml in lot A (19 samples), 0.36 ng/ml in lot B (104 samples), 5.20 ng/ml in lot C (17 samples), 1.24 ng/ml in lot D (23 samples) and 0.22 ng/ml in lot E (24 samples). ELISA of methanol extracts of rice cultures showed the presence of more than 0.1 ng/g in 3 of 15 isolates of Aspergillus, in 16 of 67 isolates of Penicillum and in 7 of 17 isolates of Eupenicillum; none was found in an isolate of Emericella. IAC-HPLC analysis revealed that P. foetidus, which is similar to A. niger and is used for the production of a Japanese alcoholic drink (shou-chuu), also produced ochratoxin A. Use of IAC-HPLC to analyse coffee beans and instant coffee power resulted in the sharp resolution of ochratoxin A without complicated clean-up steps. The IAP-HPLC technique could thus be used for mass surveys of ochratoxin A residues in biological specimens.

Direct projection from the dorsal hypothalamic area to the nucleus raphe pallidus: a study using anterograde transport with Phaseolus vulgaris leucoagglutinin in the rat.

A hypothalamic projection to the nucleus raphe pallidus of the medulla was examined using the anterograde tracing technique based on Phaseolus vulgaris leucoagglutinin (PHA-L) in the rat. After the iontophoretic application of PHA-L to the dorsal hypothalamic area, labeled fibers that finally ended in the nucleus raphe pallidus were observed descending through the most medial part of the ventral tegmental area and the nucleus reticularis tegmenti pointis to reach the medial aspect of the pyramid. Many varicose fibers forming a loose plexus were observed in the nucleus raphe pallidus, especially ventrally. The ventral surface of the pyramid and the most ventral region of the nucleus reticularis paragigantocellularis lateralis (PGCL) contained labeled varicose fibers. At the electron microscopic level, the labeled profiles in the nucleus raphe pallidus were small-sized unmyelinated axons and axon terminals. Labeled axon terminals containing spherical synaptic vesicles formed synapses on spine-like protrusions or small-sized dendritic shafts. These results strongly indicate that neurons in the dorsal hypothalamic area have a direct connection with neurons in the nucleus raphe pallidus and the ventral part of the PGCL. The possible involvement of this pathway in cardiovascular regulation was discussed.

Hypothalamic descending afferents to cells of origin of the greater petrosal nerve in the rat, as revealed by a combination of retrograde HRP and anterograde autoradiographic techniques.

Projections from the hypothalamus to cells of origin of the greater petrosal nerve were studied by the HRP and autoradiographic techniques in the rat. After an injection of [3H]amino acids into the hypothalamus and an application of HRP to the greater petrosal nerve, we found that a compact group of HRP-labeled neurons was located within a dense accumulation of silver grains in the nucleus reticularis parvocellularis. The present results show that the hypothalamus projects directly to cells of origin of the greater petrosal nerve.

A direct hypothalamic projection to the superior salivatory nucleus neurons in the rat. A study using anterograde autoradiographic and retrograde HRP methods.

The location of the superior salivatory nucleus and terminal labelings of the hypothalamic descending fibers were demonstrated in the nucleus reticularis parvocellularis using HRP and the autoradiographic techniques, respectively. When both techniques were used in the same animals, some HRP-labeled neurons were seen among the accumulations of silver grains, suggesting pericellular terminations. The present study demonstrates that the hypothalamic efferents project directly to the superior salivatory nucleus innervating salivary and lacrimal glands.

Selenium protection against mercury toxicity: high binding affinity of methylmercury by selenium-containing ligands in comparison with sulfur-containing ligands.

In determining the protection of selenium against mercury toxicity, the binding affinity of methylmercury by various selenium-containing ligands was investigated by proton magnetic resonance (PMR) spectroscopy. The most striking feature was the small J199Hg-1H value of the selenocysteamine- and selenocysteine-methylmercury complexes, namely, the high affinity of the selenohydryl group to the mercury in comparison with those of the sulfhydryl and amino groups. The order of binding affinity of the coordination groups toward methylmercury is clearly SeH greater than SH greater than or equal to Se-Se greater than NH2 greater than S-S, SeCH3, SCH3. A definite correlation was found to exist between the mercury-proton coupling constants and the chemical shifts of methyl groups of the methylmercury complexes. A relationship between the order (Se greater than S greater than NH2) of affinity for methylmercury and the basicity (or electronegativity and covalent radius) of the donor groups was also discussed. These results suggest the high covalency of the CH3Hg-Se bond, which involves dpi-dpi back bonding.