Myocardial ischemia stimulates catecholamine synthesis and catabolism in the dog adrenal medulla

The effects of regional ischemia of the myocardium upon metabolism and catabolism of catecholamines were studied in the dog adrenal medulla. Regional ischemia was induced by ligating a small branch of the left anterior descending coronary artery for 1 or 24 hours. Sham-operated controls were run in parallel. Coronary ligation for 24 hours resulted in a decrease in the level of epinephrine and an increase in the level of dopamine in the adrenal medulla, and also resulted in an increase in the activities of the phenylethanolamine-N-methyltransferase (PNMT), monoamine oxidase, and catechol-O-methyltransferase. The results after coronary ligation for 1 hour were essentially the same as those after coronary ligation for 24 hours, except that the activity of PNMT decreased. These results suggest that both synthesis and catabolism of catecholamines in the adrenal medulla are accelerated during coronary ligation for a period of 1 to 24 hours.     

Circadian variation of motor current observed in fixed rotation speed continuous-flow left ventricular assist device support

The algorithm for the physiological control provided by left ventricular assist devices (LVADs) has been controversial. In particular, little is known about the physiological control algorithm (such as for achieving physiological circadian rhythms) in continuous-flow LVADs. To investigate the existence of circadian variation, we retrospectively evaluated the LVAD flow-correlated motor current of patients supported by continuous-flow LVADs. The motor current and the pump speed were collected from the external controller every 10 min after device implantation, and the data were divided for every 30-day period, which began on midnight on the first post-operative day. The subjects were 18 patients (mean age 37.7, mean body surface area 1.71 m² at the time of operation) with dilated cardiomyopathy or dilated phase of hypertrophic cardiomyopathy. As of August 1, 2013, the patients’ median support duration was 889 days. The mean calculated dominant period of motor current variation was 24.0 h and the mean amplitude was 11.7 mA for the entire duration. The amplitude of the motor current circadian variation tended to be increased until around the fifth month. The motor current had a tendency to be relatively low during the night time and high during the day time. A significant difference was found between the night-time and day-time mean motor current for the entire duration (p < 0.05). In conclusion, the circadian variation of the motor current could be observed over long term in patients with fixed rotation speed continuous-flow LVAD support.     

AT1 receptor blockade reduces cardiac calcineurin activity in hypertensive rats

The possible role of calcineurin in the attenuation of cardiac hypertrophy and fibrosis by blockade of the angiotensin II type 1 (AT1) receptor was investigated in Dahl salt-sensitive (DS) rats. The effect of the calcineurin inhibitor FK506 was also studied. DS rats progressively developed severe hypertension when fed a diet containing 8% NaCl from 7 weeks of age. In addition, marked cardiac hypertrophy and fibrosis were apparent and the activity of calcineurin and its mRNA expression in the myocardium was increased in these animals at 12 weeks in comparison with age-matched Dahl salt-resistant rats. The abundance of angiotensin-converting enzyme (ACE) and transforming growth factor (TGF)-beta1 mRNAs was also increased in the hearts of DS rats at 12 weeks. Treatment of DS rats with a non-antihypertensive dose of the selective AT1 receptor blocker candesartan (1 mg/kg per day) or FK506 (0.1 mg/kg per day) from 7 to 12 weeks attenuated both calcineurin activity and its mRNA expression in the heart, as well as the development of cardiac hypertrophy and fibrosis, without affecting cardiac function. Treatment with candesartan, but not FK506, prevented the upregulation of ACE and TGF-beta1 gene expression. Both candesartan and FK506 prevented the load-induced induction of fetal-type cardiac genes. These results demonstrate that AT1 receptor blockade attenuates the development of cardiac hypertrophy and fibrosis as well as the activation of calcineurin, without an antihypertensive effect, in rats with salt-sensitive hypertension. Calcineurin may be downstream from TGF-beta1 in AT1 receptor-mediated angiotensin II signaling in vivo.     

Clinical usefulness of the immunostaining of the tumor markers in pancreatic cancer

The effect of the rapid immunostaining of gastrointestinal cancer-associated antigens, CA19-9, CEA, DUPAN2, and CA50 was discussed for intraoperative pathological diagnosis of pancreatic cancer. The method can be completed in only 13 minutes with microwave irradiation to accelerate the incubation of the primary antibody. Only 3 seconds of irradiation at 500 W for fresh-frozen sections produced specific antigen staining of greater intensity than that obtained with longer incubation by the conventional method. Preservation of the tissue structure was satisfactory with minimal nonspecific background staining enabling us to diagnose the intrapancreatic spread of cancer. This method was also applied to intraoperative peritoneal washing cytology. As with frozen section biopsy, the sensitivity of intraoperative cytology is greater than by the conventional staining method, which is able to achieve more precise staging of pancreatic cancers. Our rapid immunoperoxidase staining method on the cryostat section of pancreatic biopsy specimens and on cytology samples provides important information to determine an appropriate operative approach for pancreatic cancer.     

Antimicrobial susceptibility by Etest of Bartonella henselae isolated from cats and human in Japan

Bartonella henselae, a small fastidious Gram-negative bacillus, is the causative agent of cat-scratch disease (CSD). Because of difficulty in isolating the organism, there has been no report on its antibiotic susceptibility in Japan. We determined the minimal inhibitory concentrations (MICs) of eight antimicrobial agents against 32 isolates of B. henselae (31 from cats and one from a human in Japan) by the Etest method. MICs of all 32 isolates were <0.016 μg/ml for minocycline and ranged from ≤0.016 to 0.064 μg/ml for erythromycin, clarithromycin, azithromycin, ceftriaxone, and amoxicillin. MICs ranges of ciprofloxacin and gentamicin were from 0.064 to 0.25 μg/ml and from 0.5 to 3 μg/ml, respectively. All isolated strains showed high susceptibility to minocycline and macrolides antibiotics, which are currently used in the primary treatment of CSD in Japan. Although in vitro result of B. henselae susceptibility testing may not necessarily correlate with clinical response, these data are relevant in the choice of drugs for CSD treatment.     

Evidence for angiotensin II type 2 receptor-mediated cardiac myocyte enlargement during in vivo pressure overload

The pathophysiological roles of the angiotensin II type 2 receptor (AT(2)) in cardiac hypertrophy remain unclear. By the targeted deletion of mouse AT(2) we were able to prevent the left ventricular hypertrophy resulting from pressure overload, while cardiac contractile functions remained normal. This implies that AT(2) is a mediator of cardiac hypertrophy in response to increased blood pressure. The effects of AT(2) deletion were independent of activation of embryonic genes for cardiac hypertrophy. However, p70(S6k), one of the key factors in cardiac hypertrophy, was markedly and specifically reduced in the ventricles of Agtr2(-)/Y mice. We propose that p70(S6k) plays a major role in AT(2)-mediated ventricular hypertrophy. This article may have been published online in advance of the print edition. The date of publication is available from the JCI website, http://www.jci.org.     

Intraoperative peritoneal washing cytology with the rapid immunoperoxidase method using microwave irradiation

The rapid immunocytochemical staining of gastrointestinal cancer-associated antigens, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19–9), for intraoperative peritoneal washing cytology of pancreatic or biliary carcinoma can be completed in only 25 minutes by using microwave irradiation to accelerate incubation of the primary antibody. Only 3-second irradiation at 500 W for fresh smears produced specific antigen staining of malignant cells similar to that obtained with longer incubation, and the sensitivity of intraoperative cytology was greater than by the conventional staining method. The rapid immunocytochemical staining method of peritoneal washings at laparotomy can provide sensitive information for determining more aggressive therapy for intraperitoneal spread of malignant cells before closing the abdominal wall. © 1995 Wiley-Liss, Inc.     

Prevention by natural food anthocyanins, purple sweet potato color and red cabbage color, of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-associated colorectal carcinogenesis in rats initiated with 1,2-dimethylhydrazine

The potential of purple sweet potato color (PSPC) and red cabbage color (RCC), natural anthocyanin food colors, to modify colorectal carcinogenesis was investigated in male F344/DuCrj rats, initially treated with 1,2-dimethylhydrazine (DMH) and receiving 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the diet. After DMH initiation, PSPC and RCC were given at a dietary level of 5.0% in combination with 0.02% PhIP until week 36. No PSPC or RCC-treatment-related changes in clinical signs and body weight were found. Incidences and multiplicities of colorectal adenomas and carcinomas in rats initiated with DMH were clearly increased by PhIP. In contrast, lesion development was suppressed by RCC, or tended to be inhibited by PSPC administration. Furthermore, in the non-DMH initiation groups, induction of aberrant crypt foci (ACF) by PhIP was significantly decreased by RCC supplementation. The results thus demonstrate that while PhIP clearly exerts promoting effects on DMH-induced colorectal carcinogenesis, these can be reduced by 5.0% PSPC or 5.0% RCC in a diet under the present experimental conditions.