Hypothalamic regulation of histidyl-proline diketopiperazine binding sites in the rat liver

The effects of hypothalamic hormones and electrolytic lesioning of the ventromedial hypothalamic nuclei (VMH) on histidyl-proline diketopiperazine (cyclo(His-Pro] binding in the rat liver were studied. VMH-lesioning markedly decreased cyclo(His-Pro) binding in the liver. Scatchard analysis revealed that the loss of cyclo(His-Pro) binding induced by VMH lesioning was due to a decrease in the number and affinity of binding sites. Somatostatin (SS) administration decreased cyclo(His-Pro) binding. The SS-induced changes in cyclo(His-Pro) binding were due to changes in the binding affinity. On the other hand, the administration of TRH or LH-RH did not affect cyclo(His-Pro) binding in the liver, although cyclo(His-Pro) has been proposed to be a metabolite of TRH. These findings suggest that the hypothalamus may regulate the cyclo(His-Pro) binding sites in the liver probably by controlling pancreatic SS secretion, since a VMH-lesion is reported to cause hypersecretion of pancreatic SS.     

Coronary artery bypass grafting with combined arterial grafts

Coronary artery bypass grafting with combined arterial graft using the left internal mammary artery (IMA), right IMA, and the right gastroepiploic artery (GEA) was performed in 45 patients with saphenous vein graft (SVG) (29 patients) or without SVG (16 patients) from February 1989 to October 1989. The left IMA was used in all patients, the right IMA was used in 9 patients, and the GEA was used in 43 patients. Perioperative myocardial infarction was noted in two patients who had hospital deaths. Reopening the chest for postoperative bleeding was performed in two patients, and the cerebral accident was noted in one patient. Fourteen patients were operated on without the requirement for blood transfusion. Studied within 3 postoperative months, all arterial grafts were patent though the patency was 97.7% (43/44) in SVG. It is concluded that the combined arterial graft utilizing the IMAs and GEA can be used safely and effectively.     

Involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters in neonatal rat spinal cord.

1. The possible involvement of enzymatic degradation in the inactivation of tachykinin neurotransmitters was examined in the spinal cord of the neonatal rat. 2. The magnitude of substance P (SP)- or neurokinin A (NKA)-evoked depolarization of a lumbar ventral root in the isolated spinal cord preparation was increased by a mixture of peptidase inhibitors, consisting of actinonin (6 microM), arphamenine B (6 microM), bestatin (10 microM), captopril (10 microM) and thiorphan (0.3 microM). The mixture augmented the response to NKA more markedly than that to SP. 3. In the isolated spinal cord-cutaneous nerve preparation, the saphenous nerve-evoked slow depolarization of the L3 ventral root was augmented by the mixture of peptidase inhibitors in the presence of naloxone (0.5 microM) but not in the presence of both naloxone and a tachykinin receptor antagonist, GR71251 (5 microM). 4. Application of capsaicin (0.5 microM) for 6 min to the spinal cord evoked an increase in the release of SP from the spinal cord. The amount of SP released was significantly augmented by the mixture of peptidase inhibitors. 5. Synaptic membrane fractions were prepared from neonatal rat spinal cords. These fractions showed degrading activities for SP and NKA and the activities were inhibited by the mixture of peptidase inhibitors. The degrading activity for NKA was higher than that for SP and the inhibitory effect of the mixture for NKA was more marked than that for SP. Although some other fractions obtained from homogenates of spinal cords showed higher degrading activities for SP, these activities were insensitive to the mixture of peptidase inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)     

Metabolic and morphological alterations of brown adipose tissue after sympathetic denervation in rats

Effects of sympathetic denervation on biochemical and morphological changes of brown adipose tissue (BAT) were studied in rats after severing 5 intercostal nerve bundles that enter the unilateral interscapular BAT, the contralateral BAT being used as the control. Four weeks after denervation, there was no appreciable change in BAT weight or its DNA and protein contents, whereas the triglyceride content was increased significantly. However, the rate of fatty acid synthesis was decreased to about half the rate in controls. The denervated BAT was much paler than controls and contained lots of adipocytes filled with large lipid droplets, some of which were unilocular. The results are discussed with reference to changes in BAT seen after bilateral lesions of the ventromedial hypothalamus.     

Coexistence of amyotrophic lateral sclerosis and argyrophilic grain disease: A non‐demented autopsy case showing circumscribed temporal atrophy and involvement of the amygdala

We report a case of a 68‐year‐old right‐handed man with sporadic amyotrophic lateral sclerosis (ALS) and argyrophilic grain disease (AGD) having a 22‐month duration. His initial symptoms were dysarthria and swallowing difficulty at the age of 67. Subsequently bulbar palsy and pyramidal signs developed. His cognitive functions including face recognition, personality, and behavior were not changed compared with that of before the disease onset. However, magnetic resonance imaging disclosed severe right side‐predominant temporal atrophy. The neurological diagnosis was bulbar type ALS. Pathological examination disclosed histological evidence of ALS, including loss of Betz cells and lower motor neurons, corticospinal tract degeneration, and Bunina bodies. In addition, severe neuronal loss in the bilateral temporal cortex with an anterior gradient was found. Ubiquitin‐positive inclusions were encountered in the spinal anterior horn cells and hippocampal dentate gyrus, while few ubiquitin‐positive inclusions were noted in the affected temporal cortex. The amygdala, especially the basolateral nuclear group, was severely affected by neuronal loss with tissue rarefaction. Moderate neuronal loss was encountered in the parahippocampal gyrus, and to a lesser degree, in the ambient gyrus. Unexpectedly, many argyrophilic grains, coiled bodies, tau‐positive bush‐like astrocytes, pretangles, and ballooned neurons were found in the limbic system and temporal cortex. In the hippocampus, selective tau accumulation with minor neurofibrillary changes was observed in CA2 neurons. The present case suggests that (i) ALS and AGD do rarely coexist, and (ii) when ALS patients have severe temporal atrophy, not only ALS with dementia but also concurrent AGD should be considered in the differential diagnosis.     

The effect of bismuth subnitrate on cisplatin toxicity

Bismuth subnitrate (BSN), a bismuth compound medically used for antidiarrheics, was orally administered to see whether it can reduce CDDP nephrotoxicity or not. Thirteen patients aged 19 approximately 60 with ovarian cancer entered this BSN-CDDP trial. A total of thirty three courses of BSN-CDDP treatment was undergone. BSN was administered orally at a dose of 50 mg/kg for five days before CDDP therapy. CDDP was infused for two hours. No vigorous hydration or diuresis was performed. Only 2,000 ml of saline with 20 mEq per liter of KCl was given for post-hydration. The median dose of CDDP was 100 mg/m2. The renal toxicity of BSN-CDDP treatment was minimum. 82% of the courses at the sixth day after the treatment had creatinine clearance levels which were more than 80% of those before the treatment. But twenty-four hour NAG and beta 2-microglobulin excretion were significantly increased. Bone marrow suppression and gastrointestinal disturbance were commonly observed. The results of our study indicate that BSN pretreatment reduces the renal toxicity of CDDP to some extent.     

Basic and clinical studies on imipenem/cilastatin sodium in the pediatric field

Basic and clinical studies have been performed on imipenem/cilastatin sodium (MK-0787/MK-0791) in the pediatric field. Antibacterial activities of MK-0787 against 14 clinical isolates of S. aureus and 67 isolates of E. coli were determined. The MIC of MK-0787 was 0.10 microgram/ml or less against all 14 strains of S. aureus. The MIC of MK-0787 was 0.39 microgram/ml or less against all 67 strains of E. coli. The pharmacokinetics of MK-0787/MK-0791 was studied at dose levels of 10 mg/10 mg/kg and 20 mg/20 mg/kg. The peak serum levels of MK-0787 achieved approximately 1 hour after the administration of 10 mg/10 mg/kg and 20 mg/20 mg/kg doses were 38.6 micrograms/ml and 36.2 micrograms/ml, respectively. The serum half-lives were 0.8 hour and 0.9 hour, respectively. The total 6-hour urinary excretions were 82.1% and 66.7%, respectively. The MK-0787/MK-0791 was administered to 13 children with bacterial infections. The clinical results were excellent or good in all cases. The overall efficacy rate was 100%. As a side effect, diarrhea was observed in 1 patient. Abnormalities in laboratory findings observed were elevation of direct bilirubin in 1 patient, thrombocytosis in 2, and a prolonged prothrombin time in 1 patient. Based on the above results, it can be concluded that MK-0787/MK-0791 is a safe and effective drug to use for the treatment of pediatric infections.     

Left ventricular asynergy in patients with impending myocardial infarction: two-dimensional echocardiographic assessment

To determine the clinical significance of regional left ventricular asynergy in patients with impending myocardial infarction, we recorded two-dimensional echocardiograms (2DE) serially and performed coronary angiography immediately after the hospital admission in nine patients with initial impending infarction and their last anginal attacks were within 48 hours. Left ventricular asynergy on the first 2DE was observed in six of nine patients during symptom-free periods (Group A: LV asynergy group). Five of the six patients had significant coronary artery lesions (greater than or equal to 75% stenosis) in at least one major coronary artery. Intracoronary filling defects were detected in four of the five patients. Another three patients without asynergy (Group B) had significant fixed stenosis. Coronary artery spasm was observed in two patients during coronary angiography, but no patient had intracoronary filling defects. Intracoronary nitroglycerin (0.1-0.3 mg) reduced the severity of coronary artery narrowing in two patients. In addition, urokinase (240,000-480,000 IU) via the corresponding vessel (PTCR) in the remaining seven patients resulted in reduction in the severity of coronary artery stenosis in four patients, but not in the remaining three patients. Left ventricular wall movement in the asynergy group improved rapidly and no asynergy was observed by the seventh hospital day in five of the six patients. Successful PTCR treatment resulted in improvement of left ventricular wall movement. No asynergy was found in the non-asynergy group throughout their hospitalizations. These findings indicated that abnormal left ventricular wall movement is found in patients with impending myocardial infarction, even during symptom-free periods, but the wall movement gradually improves. The 2DE observations are useful for estimating the clinical status and for planning precise therapy for impending myocardial infarction.