Renal glutathione depletion and nephrotoxicity of cadmium-metallothionein in rats

Renal glutathione (GSH) concentrations were reduced approximately 80% at 4 hr after a single injection of buthionine sulfoxime (BSO) (4 mmol/kg body wt) and remained reduced for at least 16 hr in male rats. Following BSO injection, rats were injected with a nephrotoxic dose of cadmium-metallothionein (Cd-MT) (0.3 mg Cd as Cd-MT/kg body wt) and killed 1, 4, or 12 hr later. Damage to the kidney was assessed histologically and by measurement of p-aminohippuric acid (PAH) uptake into renal cortical slices. Although the renal accumulation of Cd following Cd-MT injection was significantly lower in BSO-pretreated rats as compared to nonpretreated rats, the damage to kidney was more severe. At 4 and 12 hr, both Cd-MT-induced inhibition of PAH uptake and morphological damage were significantly increased in BSO-pretreated rats. In certain experiments, the induction of renal intracellular MT synthesis by zinc pretreatment slightly decreased the renal toxicity of Cd-MT in the BSO-treated rats. The results demonstrate that although GSH depletion decreases the renal accumulation of Cd in rats injected with Cd-MT, the nephrotoxicity of Cd-MT is increased. Preinduction of MT in the kidney can only partially overcome this increase in toxicity. Therefore both GSH and intracellular MT levels can influence the renal toxicity of injected Cd-MT.     

Pseudoaneurysm of the cortical artery associated with chronic subdural hematoma--a consideration on traumatic middle cerebral artery aneurysm

A 62-year-old man was admitted to our hospital, since chronic subdural hematoma was showed after he complained of mild headache and nausea. Two years ago he had head trauma at the left parietal region after drinking. On admission there was no paresis and mild choked disc is detected. Computed tomography with contrast enhancement showed abnormal enhancement and left chronic subdural hematoma. Cerebral angiography showed an aneurysm of the angular artery. Operation was done and the aneurysm was trapped. Aneurysmal wall was histologically a pseudoaneurysm. Post-operative result was good. We considered the relationship between the cortical pseudoaneurysm and chronic subdural hematoma. We reviewed the traumatic middle cerebral artery aneurysm in the literature, 56 cases.     

Effects of chronic administration of L-arginine on vasoactive responses induced by endothelin-1 and its plasma level in streptozotocin-induced diabetic rats.

To investigate the mechanism underlying increased endothelin-1 (ET-1) release in diabetic rats, we administered L-arginine chronically to streptozotocin (STZ)-induced diabetic rats. The plasma concentrations of glucose, ET-1 and NOx (NO2- + NO3-) were all significantly raised at 10 weeks after the STZ injection. Chronic administration of L-arginine resulted in a significantly higher plasma NOx concentration and a significantly lower plasma ET-1 level at 10 weeks compared with the untreated diabetic group. ET-1 induced a biphasic vasodilator/vasoconstrictor response in the perfused isolated mesenteric arterial beds from all groups. The vasodilatation was significantly greater in diabetic rats than in age-matched controls. Chronic oral L-arginine administration had no significant effect on the enhanced ET-1-induced vasodilatation seen in the untreated diabetic rats. The vasoconstrictions induced by ET-1 and methoxamine were significantly attenuated in STZ-diabetic rats. The attenuated vasoconstrictor response to ET-1, but not that to methoxamine, was further attenuated by chronic treatment with L-arginine. We conclude that since chronic L-arginine administration not only reduced the increase in plasma ET-1 levels but also further attenuated the ET-1-induced vasoconstriction without affecting the change in vasodilatation, chronic L-arginine administration could be valuable for the treatment of the symptoms of diabetic mellitus related to ET-1.     

The effects of long term Tranilast administration on bronchial hypersensitivity in asthmatics

Tranilast is an oral antiallergic agent developed in Japan. This study investigated the effect of prolonged administration of Tranilast on the bronchial sensitivity of 18 asthmatic subjects. They were treated for either less than 3 months or more than 3 months continuously. Methacholine loading testing was used to assess bronchial reactivity, and the respiratory parameters were recorded on an Astograph. Patients treated for longer than 3 months showed a significant decrease in bronchial sensitivity (p less than 0.05). The anticholinergic and bronchodilatory properties of Tranilast were also investigated in 8 subjects. No significant anticholinergic or bronchodilatory effects were observed following a single oral dose of 100 mg of Tranilast.     

Correlation of 99mTc-MDP scintimetry and histology in cervical hip fracture

In 20 cases of fresh cervical hip fracture, treated with primary prosthetic replacement, preoperative 99mTc-MDP scintimetry was compared with histologic findings of the extracted femoral heads. The radionuclide uptake was classified into three types according to the activity distribution; overall increase, focal decrease, and overall decrease. Histologically, the location and extent of ischemic necrosis in the femoral heads were closely related to the distribution of decreased activity.