Nitric Oxide Donor NOR 3 Inhibits Ketogenesis from Oleate in Isolated Rat Hepatocytes by a Cyclic GMP-Independent Mechanism

Abstract: Studies were conducted to clarify the effects of nitric oxide donors NOR 3 (±)-(E)-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexeneamide, FK409), S1N-1 (3-morpholinosydnonimine) and SNAP (S-nitroso-N-acetylpenieillarnine) on the accumulation of cGMP and cAMP and Ca²⁺ mobilization as well as ketogenesis from oleate in isolated rat hepatocytes. NOR 3 caused inhibition of ketogenesis from oleate along with stimulation of cGMP accumulation in rat hepatocytes, whereas SIN-1 and SNAP exerted no effect on ketogenesis despite their marked stimulation of cGMP accumulation. Although the nitric oxide trapping agent, carboxy-PTIO (2-phenyl-4,4,5,5-tetramethylimidazoline-l-oxyl 3-oxide), antagonized the stimulation by NOR 3 of cGMP accumulation, it failed to modulate the anti-ketogenic action of NOR 3. Furthermore, neither 8-bromoguanosine-3′,5′-cyclic monophosphate nor N²,2′-O-dibutyrylguanosine-3′,5′-cyclic monophosphate mimicked the anti-ketogenic action of NOR 3. It is concluded in the present study that NOR 3-induced inhibition of ketogenesis in rat hepatocytes is not mediated by cGMP. The present study revealed that the remaining structure of NOR 3 from which nitric oxide had been spontaneously released had no anti-ketogenic action. We first and clearly demonstrated that nitrite production was dramatically enhanced when NOR 3 was incubated in the presence of rat hepatocytes. The mechanism whereby NOR 3 inhibits ketogenesis in rat hepatocytes will be discussed.     

Adjuvant and neoadjuvant chemotherapy for invasive bladder cancer

A total of 20 patients with primary invasive bladder cancer who underwent radical cystectomy received postoperative adjuvant chemotherapy using a CAP (cyclophosphamide, doxorubicin, and cisplatin) or modified M-VAC (methotrexate, vinblastine, pirarubicin, and cisplatin) regimen. In all, 16 of the patients were treated with CAP and 4 received the modified M-VAC regimen. Of the 20 patients, 17 had transitional-cell carcinoma with or without non-transitional-cell elements. All of the patients had tumors with a histological grade of G2 (6 cases) or G3 (14 cases). As for lymph-node metastasis, there were ten N0 cases, three N1 cases, six N2 cases, and one N3 case. Adjuvant chemotherapy was usually commenced 2 weeks after the surgery and was given every 3–4 weeks for two or three cycles. The 5-year survival rate of these 20 patients was 65.9%, whereas that of 49 patients who did not receive any adjuvant chemotherapy was 30.2%. Regarding toxicity, both of the adjuvant chemotherapy regimens used in this study were generally well tolerated. The most common toxic effects were gastrointestinal symptoms, alopecia, and myelosuppression. Another 19 patients with invasive transitional-cell carcinoma of the bladder received 2 or 3 cycles of neoadjuvant chemotherapy using the modified M-VAC or MEC (methotrexate, epirubicin, and cisplatin) regimen. Of 18 pathologically evaluable patients who underwent radical cystectomy or partial cystectomy, the stage was pT0 in 3 cases (17%), pTis in 3 (17%), pT1 in 3 (17%), and pT2 or higher in 9 (50%). The 4-year survival rate of 18 patients who received neoadjuvant chemotherapy was 71.5%. Regarding toxicity, one patient died of a bowel complication after surgery, and the complication was suggested to be drug-induced.Paper presented at the 5th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 24–25 September 1993, Hakone, Japan     

Intracranial complications resulting from frontal pyocele: Case presentation and review of experience in japan

A case of subdural empyema resulting from an acute infection of frontal cysts is reported. Urgent surgery was performed to create a right frontal burr hole, followed by an osteoplastic frontal sinusotomy and postoperative chemotherapy. Thus, this intracranial complication was successfully treated with no further sequelae. MRI was useful for clearly revealing a transtentorial herniation and the affected site of the dura mater from which bacterial infection spread intracranially. Review of rhinogenic intracranial complications in Japan shows a dramatic decrease in the mortality rate from the preantibiotics era to the pre-CT-scan era, and also from the pre–CT-scan era to the present CT-scan era. This suggests that CT scan and, more recently, MRI, have indirectly helped to reduce the mortality rate by enabling an earlier and accurate diagnosis.     

Evaluation of vascular compliance and vasoconstrictive reactions in amputated hindlimbs of rats

The vascular compliance and the contractility of vascular smooth muscle of preserved, amputated hindlimbs of rats were evaluated using a fresh blood extracorporeal circulatory system. Vascular compliance was measured under physiologic circulatory conditions (blood pressure of the amputated limb was maintained at 80–150 mm Hg [10–20 kPa]) and found not to differ significantly from that of freshly amputated limbs after storage at 4°C for 12 hours. However, after more than 24 hours of storage at 4°C, the vascular compliance decreased significantly (p < 0.01). To evaluate the contractility of vascular smooth muscle, the arterial blood pressure in the amputated limbs was transiently increased with injections of norepinephrine. The contractility could be preserved for at least 12 hours at 4°C; however, it decreased markedly after more than 24 hours. The vascular compliance and vasoconstrictive reactions of the amputated limbs were maintained for at least 12 hours at 4°C.     

Marshall-Smith Syndrome: Report of a Case and Review of the Literature

ABSTRACT Marshall-Smith syndrome is a rare disorder characterized by accelerated skeletal maturation, bullet-shaped proximal and middle phalanges, dysmorphic facial features, and failure to thrive, and is often associated with mental retardation of variable degree. We describe an 8-month-old female with this syndrome, who has a hypoplastic corpus callosum and extreme upper airway obstruction requiring tracheostomy. Also, we review the previous reports of this syndrome since 1971 (Marshall et al., 1971).     

A dopamine infusion decreases propofol concentration during epidural blockade under general anesthesia

PURPOSE: It is common clinical practice to use dopamine to manage the reduction in blood pressure accompanying epidural blockade. As propofol is a high-clearance drug, propofol concentrations can be influenced by cardiac output (CO). The purpose of the present study was to investigate the effects of dopamine infusions on propofol concentrations administered by a target-controlled infusion system during epidural block under general anesthesia. METHODS: 12 patients undergoing abdominal surgery were enrolled in this study. Anesthesia was induced with propofol and vecuronium 0.1 mg.kg(-1), and maintained using 67% nitrous oxide, sevoflurane in oxygen and constant infusion of propofol. Propofol was administered to all subjects via target-controlled infusion to achieve a propofol concentration at 6.0 microg.mL(-1) at intubation and 2.0 microg.mL(-1) after intubation. Before and after the administration of 10 mL of 1.5% mepivacaine from the epidural catheter and dopamine infusion at 5 microg.kg(-1).min(-1), CO and effective liver blood flow (LBF) were measured using indocyanine green. Blood propofol concentration was also determined using high-performance liquid chromatography. RESULTS: At one hour after epidural block and dopamine infusion, CO was significantly increased from 4.30 +/- 1.07 L.min(-1) to 5.82 +/- 0.98 L.min(-1) (P < 0.0001), and effective LBF was increased 0.75 +/- 0.17 L.min(-1) to 0.96 +/- 0.18 L.min(-1) (P < 0.0001). Propofol concentration was significantly decreased from 2.13 +/- 0.24 microg.mL(-1) to 1.59 +/- 0.29 microg.mL(-1) (P < 0.0001). CONCLUSIONS: Propofol concentrations decrease with an increase in CO, suggesting the possibility of inadequate anesthetic depth following catecholamine infusion during propofol anesthesia.     

Clinical significance of faecal calprotectin levels in patients with ulcerative colitis]

AIMS: To assess the clinical significance of faecal calprotectin levels (a neutrophil protein) in patients with ulcerative colitis (UC). METHODS: 25 patients with UC provided stool samples for calprotectin assay and the amount of calprotectin was related to UC disease activity index in each patient. Of 25 patients 4 with prednisolone refractory UC received 10 granulocyte and monocyte adsorption apheresis (GMCAP) sessions of 60 minutes duration, flow rate 30 mL per minute for 10 consecutive weeks. RESULTS: Calprotectin level in consecutive faecal samples from three patients was stable. However, increased calprotectin levels were significantly (p < 0.005) associated with Matts's endoscopic index, reflecting the level of colorectal inflammation. The 4 patients who received GMCAP therapy had a clinical activity index < 2 at week 7, the calprotectin level declined with improving Matts' index. CONCLUSIONS: Assay of faecal calprotectin holds promise as a sensitive biomarker to identify colorectal inflammation.     

Snoring associated with Ondine's curse in a patient with brainstem glioma.

Ondine's curse is an uncommon type of sleep apnea syndrome characterized by failure of automatic respiration. We present an adult patient with brainstem glioma who presented with snoring and Ondine's curse as the only symptoms. CASE REPORT: A 52-year-old female was brought to the hospital by a fellow resident due to exceptionally loud snoring. During the hospitalization, Ondine's curse was diagnosed after monitoring using Apnomonitor 5 (Chest Co., Tokyo), a cheap, non-invasive respiratory monitoring procedure. MRI and MR spectroscopy revealed a brainstem glioma. After radiation therapy, clinical response was documented using repeat apnomonitoring. CONCLUSION: Exceptionally loud snoring in non-obese adult patients with sleep apnea may be an early feature of a brainstem space-occupying lesion. Overnight sleep respiratory evaluation and neuroimaging should be considered in such instances.     

Risk factors for IgA nephropathy: a case-control study with incident cases in Japan.

BACKGROUND/AIM: Our previous study with prevalent cases suggested that some genetic, immunological and lifestyle-related factors increased the risk of immunoglobulin A nephropathy (IgAN). To confirm this hypothesis, we conducted another case-control study. METHODS: The study included 116 incident cases and 276 sex-, age- and residence-matched controls in central Japan. Information on family and individual history and on lifestyle was collected using a self-administered questionnaire. The strength of association between IgAN and a potential risk factor was assessed by calculating an odds ratio. RESULTS: A family history of chronic glomerulonephritis, susceptibility to the common cold, episodes of tonsillitis in the preceding year, preference for salty foods and a high intake of rice and n-6 polyunsaturated fatty acids (PUFA) were associated with an increased risk of IgAN. Coffee consumption and dietary calcium intake were somewhat negatively related to the risk. A significance of alcohol drinking, use of vitamin supplements, consumption of raw eggs and intake of nutrients other than n-6 PUFA and calcium, though previously suggested, was not shown in the present study. CONCLUSION: Our findings imply that some genetic factors, immune response to infections in the upper respiratory tract and nutritional imbalance would promote the development of IgAN.