The new role of disodium cromoglycate in the treatment of adults with bronchial asthma.

BACKGROUND: Viral infection of the respiratory tract in patients with asthma is one of the most frequent causes of exacerbation of asthmatic symptoms. Disodium cromoglycate (DSCG) is a commonly used anti-asthmatic medicine with many beneficial biochemical and physiological effects. The purpose of this study was to investigate the efficacy of DSCG against colds when used in clinical practice. METHODS: A questionnaire survey to determine the efficacy of DSCG was undertaken in 220 adult patients with asthma (81 male, 139 female; mean age: 54.1 +/- 13.7 years and 60.1 +/- 12.7 years, respectively) from April to September 2004 at the Miyatake Asthma Clinic. RESULTS: The duration of DSCG inhalation therapy was not less than 5 years in more than half of the patients. The mean daily DSCG dose at the time of the questionnaire survey was 40mg/day in over 50% of all patients. After DSCG was added to inhaled corticosteroid (ICS) combination therapy, 56.4% of the patients rated their condition as "improved", and 66.4% of the patients felt that the frequency of colds they had caught had decreased while DSCG was added to ICS. CONCLUSIONS: DSCG inhalation therapy is a useful additional treatment following ICS to alleviate asthma symptoms, and to prevent colds in adult patients with asthma.     

Evaluation of markers to estimate volume status in hemodialysis patients: atrial natriuretic peptide, inferior vena cava diameter, blood volume changes and filtration coefficients of microvasculature

Relationships among five markers of volume status - cardio-thoracic ratio (CTR), atrial natriuretic peptide (ANP), inferior vena cava diameter at quiet expiration (IVCe), blood volume change (Delta BV/TUF) during ultrafiltration and filtration coefficients of microvasculature (Lpst) - were investigated. Fifty stable hemodialysis patients were enrolled. The CTR was measured before hemodialysis (HD), and ultrasonic measurement of IVCe and sample collection for ANP were performed shortly after HD. Lpst and Delta BV/TUF were calculated using a CRIT-LINE monitor. Overhydrated patients determined by each marker (OVERctr, OVERivc, OVERanp, OVERlp and OVERbv) were compared. The agreement of volume status determined by each marker was assessed by kappa value, and the sensitivity and specificity of each marker to distinguish overhydrated patients were analyzed by a receiver-operating characteristic (ROC) curve. IVCe, ANP, Delta BV/TUF and Lpst, significantly correlated with each other. The correlation coefficients of Lpst with IVCe, ANP and Delta BV/TUF were higher than the others. The kappa value between ANP and Lpst was the highest. OVERanp was the highest, then OVERlp, OVERivc and OVERbv, in this order. The OVERlp and OVERivc patients were completely included in OVERanp. All patients, except one OVERbv patient, were included in OVERlp. The relatively high distinguishing ability of Lpst was demonstrated by ROC analysis. These results suggest that the determination of overhydration solely by ANP was an overestimation and by Delta BV/TUF was an underestimation. The relatively high correlation coefficients of Lpst with other markers, as well as its distinguishing ability, suggest that Lpst fluctuates in close relation to other markers.     

Pure topographical disorientation following a right forceps major of the splenium lesion: a case study

A 72-year-old man with pure topographical disorientation following a focal hemorrhage in the right forceps major of splenium was assessed at 2 weeks and 3 months after the onset. Initially, he could identify familiar buildings and landmarks, but noted topographical disorientation, dysfunction in sense of quarters, and in visuo-spatial function. The improvement of topographical disorientation was attained in 3 months, while the inability of the sense of quarters and manipulating visuo-spatial information remained unchanged. These results suggested the heading disorientation was accompanied with impaired sense of quarters, although disabled sense of quarters continued beyond the recovery of heading disorientation.     

Sprouty2 regulates growth and differentiation of human neuroblastoma cells through RET tyrosine kinase

The Sprouty (SPRY) family of proteins includes important regulators of downstream signaling initiated by receptor tyrosine kinases. In the present study, we investigated the role of SPRY proteins in intracellular signaling via the RET receptor tyrosine kinase activated by glial cell line-derived neurotrophic factor (GDNF). Expression of SPRY1, SPRY2, SPRY3 and SPRY4 in HEK293T cells transfected with RET and GDNF receptor family alpha1 (GFRalpha1) genes significantly reduced sustained ERK activation as well as ELK-1 activation. Because expression of SPRY2 was efficiently induced by GDNF in TGW human neuroblastoma cells expressing RET and GFRalpha1, we further investigated the role of SPRY2 in the growth and differentiation of TGW cells. Expression of wild-type SPRY2 (WT-SPRY2) decreased the growth of TGW cells. In contrast, expression of a dominant negative form of SPRY2 (MT-SPRY2, with a mutated tyrosine residue) enhanced cell proliferation. In addition, expression of WT-SPRY2 reduced GDNF-dependent neurite outgrowth of TGW cells, whereas expression of MT-SPRY2 enhanced it. Taken together, our results suggest that SPRY2 regulates GDNF-dependent proliferation and differentiation of TGW neuroblastoma cells mediated by RET tyrosine kinase.     

Sesamin, a lignan of sesame, down-regulates cyclin D1 protein expression in human tumor cells

Sesamin is a major lignan constituent of sesame and possesses multiple functions such as antihypertensive, cholesterol-lowering, lipid-lowering and anticancer activities. Several groups have previously reported that sesamin induces growth inhibition in human cancer cells. However, the nature of this growth inhibitory mechanism remains unknown. The authors here report that sesamin induces growth arrest at the G1 phase in cell cycle progression in the human breast cancer cell line MCF-7. Furthermore, sesamin dephosphorylates tumor-suppressor retinoblastoma protein (RB). It is also shown that inhibition of MCF-7 cell proliferation by sesamin is correlated with down-regulated cyclin D1 protein expression, a proto-oncogene that is overexpressed in many human cancer cells. It was found that sesamin-induced down-regulation of cyclin D1 was inhibited by proteasome inhibitors, suggesting that sesamin suppresses cyclin D1 protein expression by promoting proteasome degradation of cyclin D1 protein. Sesamin down-regulates cyclin D1 protein expression in various kinds of human tumor cells, including lung cancer, transformed renal cells, immortalized keratinocyte, melanoma and osteosarcoma. Furthermore, depletion of cyclin D1 protein using small interfering RNA rendered MCF-7 cells insensitive to the growth inhibitory effects of sesamin, implicating that cyclin D1 is at least partially related to the antiproliferative effects of sesamin. Taken together, these results suggest that the ability of sesamin to down-regulate cyclin D1 protein expression through the activation of proteasome degradation could be one of the mechanisms of the antiproliferative activity of this agent.     

Testing various fruits for anti-thrombotic effect: i. Mulberries

Prevention of arterial thrombotic disease has high priority in developed countries. As inappropriate diet predispose to acute thrombotic events, regular intake of an antithrombotic diet may be a convenient and effective way of prevention. The present study was performed to examine antithrombotic effect of mulberry varieties. A shear-induced in vitro platelet reactivity/thrombolysis test (Gorog Thrombosis Test) was used to screen for antiplatelet and thrombolytic activities. In case of effectiveness, it was followed by an in vivo test of laser-induced thrombosis in mice. Antioxidant capacity was assessed by superoxide anion and radical scavenging activities. Total polyphenolics, anthocyanin and citrate contents were also measured. The tested varieties showed different effect in vitro on platelet reactivity and endogenous thrombolytic activity. Varieties inhibiting platelet reactivity were antithrombotic in vivo regardless inhibition or enhancement of thrombolysis. Those mulberry varieties, which enhanced platelet reactivity in vitro, were prothrombotic only if inhibitory activity on endogenous thrombolysis coexisted with the platelet effect. Antioxidant activities and polyphenolics content did not affect platelets and the overall thrombotic status. However, antioxidant activities and polyphenolics content significantly correlated with the endogenous thrombolytic activity. These data showed that mulberry varieties can be grouped into subclasses with either anti- or prothrombotic activities. Antioxidant activities and polyphenolic contents do not affect platelets but may enhance endogenous thrombolysis, thus causing an overall antithrombotic effect.     

Genome wide screen identifies microsatellite markers associated with acute adverse effects following radiotherapy in cancer patients

Background  

The response of normal tissues in cancer patients undergoing radiotherapy varies, possibly due to genetic differences underlying variation in radiosensitivity.     

JPN Guidelines for the management of acute pancreatitis: diagnostic criteria for acute pancreatitis

The currently used diagnostic criteria for acute pancreatitis in Japan are presentation with at least two of the following three manifestations: (1) acute abdominal pain and tenderness in the upper abdomen; (2) elevated levels of pancreatic enzyme in the blood, urine, or ascitic fluid; and (3) abnormal imaging findings in the pancreas associated with acute pancreatitis. When a diagnosis is made on this basis, other pancreatic diseases and acute abdomen can be ruled out. The purpose of this article is to review the conventional criteria and, in particular, the various methods of diagnosis based on pancreatic enzyme values, with the aim of improving the quality of diagnosis of acute pancreatitis and formulating common internationally agreed criteria. The review considers the following recommendations:

• — Better even than the total blood amylase level, the blood lipase level is the best pancreatic enzyme for the diagnosis of acute pancreatitis and its differentiation from other diseases.
• — A pivotal factor in the diagnosis of acute pancreatitis is identifying an increase in pancreatic enzymes in the blood.
• — Ultrasonography (US) is also one of the procedures that should be performed in all patients with suspected acute pancreatitis.
• — Magnetic resonance imaging (MRI) is one of the most important imaging procedures for diagnosing acute pancreatitis and its intraperitoneal complications.
• — Computed tomography (CT) is also one of the most important imaging procedures for diagnosing acute pancreatitis and its intraabdominal complications. CT should be performed when a diagnosis of acute pancreatitis cannot be established on the basis of the clinical findings, results of blood and urine tests, or US, or when the etiology of the pancreatitis is unknown.
• — When acute pancreatitis is suspected, chest and abdominal X‐ray examinations should be performed to determine whether any abnormal findings caused by acute pancreatitis are present.
• — Because the etiology of acute pancreatitis can have a crucial influence on both the treatment policy and severity assessment, it should be evaluated promptly and accurately. It is particularly important to differentiate between gallstone‐induced acute pancreatitis, which requires treatment of the biliary system, and alcohol‐induced acute pancreatitis, which requires a different form of treatment.

     

Immediate effect of Shakuyaku-kanzo-to on muscle cramp in hemodialysis patients

We administered 2.5 g of Shakuyaku-kanzo-to granule to 61 patients who had muscle cramp during hemodialysis (HD) sessions and examined its immediate effects. We selected 10 patients who wanted to take the drug at home, out of cases, for whom the drug was effective on the study described above and had them take the drug in the same way at the beginning of muscle cramp at home examined the effects. In the study during HD sessions, muscle cramp and its associated pain disappeared in 5.3 +/- 3.9 min on average in 54 out of 61 cases. In the study of patients who took the drug at home, muscle cramp disappeared within 10 min in all cases. Shakuyaku-kanzo-to is thought to be very useful for muscle cramp during HD sessions of hemodialized patients because it has immediate effects by its oral administration on the occasion of cramp. With regard to the muscle cramp, which appears at home after HD sessions, the patients can cope with it by taking the drug by themselves. This is an epoch-making therapy, for it was impossible to cope with muscle cramp except in hospitals because the therapy of muscle cramp was limited to intravenous infusion of hypertonic solutions of dextrose, mannitol, and saline during HD sessions.