Trace metals such as zinc, manganese, and iron are necessary for the growth and function of the brain. The transport of trace metals into the brain is strictly regulated by the brain barrier system, i.e., the blood-brain and blood-cerebrospinal fluid barriers. Trace metals usually serve the function of metalloproteins in neurons and glial cells, while a portion of trace metals exists in the presynaptic vesicles and may be released with neurotransmitters into the synaptic cleft. Zinc and manganese influence the concentration of neurotransmitters in the synaptic cleft, probably via the action against neurotransmitter receptors and transporters and ion channels. Zinc may be an inhibitory neuromodulator of glutamate release in the hippocampus, while neuromodulation by manganese might mean functional and toxic aspects in the synapse. Dietary zinc deficiency affects zinc homeostasis in the brain, followed by an enhanced susceptibility to the excitotoxicity of glutamate in the hippocampus. Transferrin may be involved in the physiological transport of iron and manganese into the brain and their utilization there. It is reported that the brain transferrin concentration is decreased in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease and that brain iron metabolism is also altered. The homeostasis of trace metals in the brain is important for brain function and also for the prevention of brain diseases.
We studied the color change of phenothiazines and metal-containing drugs after compound formation, followed by use of FT-Raman spectrocopy to observe any structural changes in them. When 6 phenothiazines (thioridazine hydrochloride, prochlorperazine maleate, levomepromazine maleate, chlorpromazine phenolphthalinate, fluphenazine maleate and perphenazine fendiate) formed compounds with natural aluminum silicate, the color change was accompanied by a shift of FT-Raman signals. These changes could be attributed to the structural changes of phenothiazines. This present observation can be then used in advance to avoid coloration of phenothiazines during preparative procedures with metal-containing drugs such as antacids.
In the present study, we analyzed the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutrophil counts in cancer patients undergoing chemotherapy using a previously developed pharmacokinetic/pharmacodynamic model.7) The time profiles of neutrophil counts in blood after repeated administration of rhG-CSF to lung cancer patients undergoing chemotherapy could be analyzed by this model by considering the inhibition of neutrophil production by antineoplastic drugs. Although deviation was observed between the predicted and observed neutrophil counts in ovarian cancer patients, it may be possible to use this model for determining a rational dosage regimen of rhG-CSF for patients undergoing chemotherapy.
The present study investigated the effects of Ginkgo biloba extract and its flavonoid fractions on α-amylase and α-glucosidase activity in vitro. Ginkgo biloba extracts and their flavonoid fraction significantly inhibited α-amylase and α-glucosidase activity in vitro. Furthermore, Ginkgo biloba extracts and their flavonoid fraction reduced the elevation of rat plasma glucose level after oral administration of various saccharinity agents. In addition, we examined the effects of the flavonoid fraction isolated from Ginkgo biloba extracts on the plasma glucose level in streptozotocin-induced diabetic rats. When flavonoid fractions were orally administered to the rats three times daily for 9 days, plasma glucose concentrations were decreased compared with those in the water treatment group. Furthermore, flavonoid fractions reduced the elevation of rat plasma glucose levels after oral administration of sucrose and glucose in streptozotocin-induced diabetic rats.
KiBank is a database for computer-aided drug design and consists of binding affinities and chemical and target protein structures. Each chemical or protein structure with hydrogen atoms added was optimized by energy minimization and stored in PDB or MDL MOL file format, so that the structural data can be directly used for in silico binding studies. To describe the extent of inhibition, the inhibition constant (Ki) value is used to simplify comparisons of strengths among chemical-protein bindings. As of April 2004, KiBank contained 142 proteins, over 5000 chemicals, and over 6000 binding affinity values that were published in peer-reviewed journals. The binding affinity values are currently mostly for membrane and nuclear receptors but are soon being expanded to other drug targets. KiBank is updated daily and can be accessed on the Web at http://kibank.iis.u-tokyo.ac.jp/at no charge.
In recent years, there have been many attempts to reuse molten slag. Molten slag is obtained through further treatment of incinerated ash produced in the disposal process of garbage or sewage sludge and is used in building materials, such as brick. To establish the safety of such slag, its physical properties and metal contents were investigated in this study. After examining the physical and chemical characteristics of 13 forms of slag made using different methods, no differences were observed and it was judged that reuse is possible. There was little elution of toxic metals in the elution test when water was used as a solvent. On the other hand, when acid and alkali were used, the elution of toxic metals tended to become greater.
The effect of incadronate, a third-generation bisphosphonate, was evaluated in rats with corticosteroid-induced osteopenia. Male Wistar rats were treated with methylprednisolone acetate (1 mg/kg, s.c.) once daily, 3 days a week for 12 weeks. Other groups received simultaneous treatment with methylprednisolone acetate and incadronate (0.03, 0.3 or 3 mg/kg, p.o.); incadronate was given once daily, 6 days a week for 12 weeks. Bone mineral densities (BMDs) of the second lumbar (L2) vertebra as well as the ultimate compressive strength of the fifth lumbar (L5) vertebra decreased. Incadronate dose-dependently inhibited the loss of L2 BMDs and the decrease in strength of the L5 vertebrae. These results suggest that incadronate may be effective in treating osteopenia accompanying corticosteroid therapy.
Serum albumin is widely used for the treatment of hypovolemia, shock, hyperbilirubinemia or acute liver failure. However, serum albumin itself may have a significant effect on the action, elimination or distribution of other medications in blood which may affect the outcome of the treatment. Besides, it is also expensive and, most important, can be a carrier for many life-threatening diseases such as AIDS. The objective of this study is to evaluate the serum albumin utilization in inpatient at a private hospital in Bangkok, Thailand. Descriptive, retrospective study was designed to monitor the 25% w/v serum albumin orders over a four-month period. The background information, doses and rational of serum albumin orders, other medication orders, side effects, the interaction between serum albumin and other medications, the laboratory results and also clinical outcome of the patients were recorded. From the medication orders of 74 inpatients, there were 104 orders of serum albumin for 9 indications. The most common indications were hypoalbuminemia (48%) and cirrhosis (9%). From the total number of serum albumin orders, there were only 67 orders (64.4%) prescribed with rational dose and duration under appropriate indications. Totally about 35.6% of serum albumin orders were prescribed with improper indications such as edema, anemia or coronary artery bypass grafting. Out of 35.6%, 14% of the orders were prescribed to contraindicated patients. No side effect of serum albumin infusion was found during this study. The result indicates the over-utilization of serum albumin and specific guideline for using this agent should be set in every hospital.