Minocycline attenuates hyperlocomotion and prepulse inhibition deficits in mice after administration of the NMDA receptor antagonist dizocilpine.

The present study was undertaken to examine whether the second generation antibiotic drug minocycline attenuates behavioral changes (eg, acute hyperlocomotion and prepulse inhibition (PPI) deficits) in mice after the administration of the N-methyl-D-aspartate (NMDA) receptor antagonist (+)-MK-801 (dizocilpine). Dizocilpine (0.1 mg/kg)-induced hyperlocomotion was significantly attenuated by pretreatment with minocycline (40 mg/kg). Furthermore, the PPI deficits after a single administration of dizocilpine (0.1 mg/kg) were attenuated by pretreatment with minocycline (10, 20, or 40 mg/kg), in a dose-dependent manner. Moreover, in vivo microdialysis study in the free-moving mice revealed that pretreatment with minocycline (40 mg/kg, i.p.) significantly attenuated the increase of extracellular dopamine (DA) levels in the frontal cortex and striatum after administration of dizocilpine (0.1 mg/kg), suggesting that the inhibition of dizocilpine-induced DA release by minocycline may, at least in part, be implicated in the mechanism of action of minocycline with respect to dizocilpine-induced behavioral changes in mice. These findings suggest that minocycline could attenuate behavioral changes in mice after the administration of the NMDA receptor antagonist dizocilpine. Therefore, it is possible that minocycline would be a potential therapeutic drug for schizophrenia.     

Tissue distribution and excretion of hexabromobenzene and its debrominated metabolites in the rat

Tissue distribution and excretion of hexabromobenzene (HBB) and some metabolites were studied in male Wistar rats administered a single oral dosage of HBB.Most of the HBB dosage was absorbed by the intestinal tract and it was rapidly metabolized and distributed throughout the body as the debrominated metabolites, pentabromobenzene (PeBB), tetrabromobenzene (TeBB) and tribromobenzene (TrBB). The time courses of HBB, PeBB and TeBB concentrations in the tissues were roughly classified into several types, and debromination of HBB was found to take place stepwise.The reductive debromination of HBB occurs by metabolic enzymes in the liver rather than microbes in the intestine.     

Blood purification procedures and their related short- and long-term effect on patients.

At present, approximately 1 million patients are on chronic hemodialysis in the world. Some patients have been dialyzed for more than 20 years. However, chronic hemodialysis produces a new type of disease known as chronic hemodialysis syndrome. Procedurally induced immunomodulation may be the cause of this syndrome. Hematological changes imposed by this extracorporeal circulation for hemodialysis are discussed in this article. A comparison with procedurally induced immunomodulation by apheresis procedures is also provided. This repeated exposure of the blood-to-blood purification device with a large foreign surface produces quite substantial immunological effects to the patient. Thus, further studies were necessary to analyze more clearly the adaptation mechanism of the human defense system. On the basis of these studies, the following conclusion could be derived. Typically, Stage 1, human adaptation to the implanted or applied man-made machine, would be 48 h and could be divided into 3 phases. They would be Phase I (15-30 min) leukocyte storage, Phase II (2-24 h) leukocyte release, and Phase III (24-48 h) completion of the proper leukocyte response. To adapt hematologically in 48 h, the patient may experience 3 phases of adaptation reactions. When patients are subjected to extracorporeal circulation, the immunosuppressive state of hemodialysis is hypothesized through these studies.     

Renal Effects of Multiple Infusion of Pyridoxalated-Hemoglobin-Polyoxyethylene Conjugate (PHP) Solution in Dogs

Abstract: Pyridoxalated-hemoglobin-polyoxyethylene conjugate (PHP), which is made from out-dated human red blood cells by two major chemical modifications, namely pyridoxalation and conjugation with polyoxyethylene (POE), is currently under development as a physiological oxygen carrier. This study assessed the effects of PHP-88 solution, which contains 8% (wt/vol) each of hemoglobin (Hb) and maltose, on renal function when it was infused 3 times every other day into the intact circulation of 8 dogs (5 dogs for the PHP group and 3 for the control group; 20 ml/kg for the first infusion, and 10 ml/kg each for the second and third infusions, at the rate of 2.5 ml/h/kg). Serial determinations of glomerular filtration rate (GFR) and renal plasma flow (RPF) were carried out pre- and postinfusion for up to 3 months along with measurements of blood and urine analyses, urine output rate, fractional excretion of sodium (FES), and free water clearance (C_H2O). The results showed that plasma colloid osmotic pressure (COP) elevated an average of 3.3 mm Hg (p = 0.0085), and GFR and RPF tended to increase by 13% (NS) and 38% (NS), respectively, immediately after the third infusion with PHP solution. Urine output rate increased during and after the infusion, and FES and C_H2O also increased for 24 h after the infusion in both groups. Blood urea nitrogen, serum creatinine, and serum Na⁺ concentrations were not affected greatly by the infusions, but hematocrit was decreased by 8% in the PHP group, indicating approximately a 42% expansion of plasma volume. These changes were observed to return to their preinfusion levels by 1 week postinfusion. Renal histology of the PHP group obtained at 2 weeks postinfusion revealed vacuole formation in the proximal tubules which was not associated with any pathologic changes indicative of cell death or regeneration. In 4 out of 5 dogs at 3 months postinfusion (necropsy), the vacuoles were not present. Though urinary N-acetyl β-glucosaminidase (NAG) activity had significantly increased after infusion, it returned to the preinfusion level by 1 month postinfusion. No detrimental effect of vacuoles on the assessed renal tubular functions was confirmed in the present study. The result demonstrated that multiple infusions of PHP solutions were well tolerated in normal dogs, and the observed effects were conceived predominantly attributable to the physiological response of the kidneys to an oncotic load into the circulation, which produced plasma volume expansion.     

Aneurysms of the anterior communicating artery and subclavian artery in association with congenital absence of unilateral internal carotid artery]

We encountered a rare case of unilateral internal carotid arterial defect complicated with anterior communicating aneurysm and subclavian artery aneurysm. The patient was a 56-year-old man in whom cerebral angiography and 3D-CTA revealed defects in the right internal carotid artery and the right carotid canal, and an unruptured aneurysm in the anterior communicating artery. In addition, the patient was also found to have an unruptured aneurysm in the right subclavian artery. As both the aneurysms were considered to have a high risk of rupture and such subclavian aneurysms were likely to cause an embolism, radical surgery was performed for each aneurysm. The postoperative course was uneventful, and the patient was discharged without ambulatory limitations. Although the defect in the internal carotid artery is a relatively rare vascular deformity, the incidence of cerebral aneurysm is about 30% in such cases due to the marked hemodynamic stress involved. On the other hand, there have been only two previous case reports of internal carotid arterial defect complicated with a subclavian aneurysm. Moreover, there have been no previous reports of internal carotid arterial defect complicated with both an intracranial aneurysm and a subclavian aneurysm, as observed in the present case. Thus, this case was very rare and is reported here.     

The study of intratumoral PO2 in brain tumors

The aim of this study was to evaluate the hypoxic cells in the human brain tumor in vivo. Untreated 16 cases of brain tumor were analysed. During the surgery for the purpose of removal of the tumor, needle type-O2 sensors were inserted into femoral artery and in brain tumor to measure PaO2 and intratumoral O2 pressure. A plate type O2 sensor was put on the surface of surrounding brain cortex to measure cortical O2 pressure. These O2 sensors for this study is able to measure O2 pressure continuously and to observe these three O2 pressure simultaneously. Operations were performed endotracheal anesthesia under inhalation of ethrane with maintaining systolic blood pressure 120 mmHg. Setting the rate of O2 and N2O gas inhalation 1/3, PaO2 revealed about 110 mmHg which is similar value as physiological state--1 ATM, air inhalation--. The value of TuO2 and BrO2 were revealed 15.3 +/- 2.3 (mean +/- SE) mmHg and 59.8 +/- 6.5 (mean +/- SE) mmHg. According to these results, it might be said that hypoxic fraction surely exist intratumoral tissue. It is also well known that O2 removes from higher pressure zone to lower pressure zone after O2 was diffused from red blood cell in brain tissue. It might be also mentioned that much lower hypoxic fraction than the value of this study is existing intratumoral tissue. It has long been recognized that hypoxia influences the response of cells and tissues to radiation. However, they have been suspected on the basis of experimental data in vitro. This study showed hypoxic fraction in human brain tumor tissue in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)