Degradation of Clodinafop Propargyl by Pseudomonas sp. Strain B2

Using clodinafop propargyl (CF) as a sole carbon, nitrogen and energy source, a CF-degrading bacterial strain was isolated from crop soil field. This strain was identified as Pseudomonas sp. strain B2 by 16S rRNA gene sequence analysis. 87.14 % CF was degraded out of initial provided 80 mg/L CF. Degradation of CF was accompanied by release of chloride ion. The optimal pH and temperature for the growth of B2 were 7.0 and 30°C, respectively in the mineral salts medium supplemented with CF. An actively growing culture of strain B2 degraded CF to clodinafop acid and 4-(4-Chloro-2-fluoro-phenoxy)-phenol within 9 h, as determined by GC–MS analysis. A metabolic pathway for the degradation of CF by B2 has been proposed.     

Dysregulation of phosphatidylinositol 3-kinase and downstream effectors in human breast cancer

Phosphatidylinositol 3-kinase (PI3-K) is a growth factor-activated transforming lipid (and protein) kinase, involved in cell motility and invasion, that has multiple effectors. Relatively little is known about its expression and enzymatic activity in human breast cancer. Since growth factor receptors are amplified in breast cancer, and the tumor suppressor PTEN may be mutated in human breast cancer, it was hypothesized that PI3-K and its downstream effectors would be activated in this disease. In 11 resected tumors analyzed for expression of this kinase, a mean 3-fold increase in protein expression was observed over the corresponding adjacent control tissue. Using an in vitro lipid kinase assay of the immunoprecipitated PI3-K protein, a greater than 2-fold increase in activation was observed. These changes were observed in the absence of an activation of either protein kinase B (PKB, akt1) or p70 S6 kinase (p70 S6K). However, p21-activated kinase (Pak), p38 mitogen-activated protein kinase (p38 MAPK) and mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK 2) were all overexpressed and demonstrated increased enzyme activity. It may be concluded that aberrant mitogenic signaling in human breast cancer in vivo involves Pak, p38 MAPK and MAPKAPK2 downstream of PI3-K, but neither of PKB or p70 S6K. It is proposed that this pathway may serve as a useful targeting nexus for investigation of small molecule inhibitors in human breast cancer.     

Genetic fingerprinting of Theileria parva using a telomeric DNA probe

 A cloned Theileria parva telomeric DNA sequence, designated pTpUtel, was used to characterize T. parva stocks and clones by hybridization to EcoRI-digested DNA. Eight of the nine T. parva stocks tested were discriminated by the telomeric restriction-fragment-length polymorphisms (RFLPs). Two isolates derived from buffalo 7014 by tick feeding on different occasions were also differentiated using the probe. The probe gave comparable results on purified piroplasm or schizont-infected lymphocyte DNA and did not cross-hybridize with uninfected bovine DNA. The telomeric restriction pattern of a cloned T. parva parasite remained identical after four passages through ticks and cattle. The telomeric sequence therefore represents a useful additional tool for analysis of theileriosis epidemiology. Received: 25 May 1995 / Accepted: 25 August 1995     

How patient involvement in care is improving service provision

An emphasis on public and service-user involvement runs through the core initiatives of the modernisation agenda as outlined in The NHS Plan (Department of Health, 2000) and related policy documents. This article discusses problems that have prevented the NHS from being responsive to the views of service users and what the implementation of policies can offer in terms of overcoming such problems. In addition, initiatives and other ways of identifying and delivering public or patient needs are considered.     

An open-label comparison of the effects of simvastatin and niacin alone and combined on the lipid profile and lipoprotein (a) level in an Indian population with dyslipidemia

Abstract

Background:

Patients with dyslipidemia often require the use of >1 lipid-altering agent to achieve the target levels recommended by the National Cholesterol Education Program Adult Treatment Panel III.

Objective:

The aim of this study was to compare the effects of simvastatin and niacin alone and combined on the lipid profile and lipoprotein (a) (Lp[a]) level in an Indian population with dyslipidemia.

Methods:

This 12-week, open-label, nonrandomized study was conducted at the Departments of Pharmacology and Medicine, Government Medical College, Amritsar (Punjab), India. Patients aged 30 to 70 years with dyslipidemia were eligible. Patients were assigned to 1 of 3 treatment groups. Group 1 received simvastatin 20 mg/d for 12 weeks. Group 2 received niacin at doses of 375 mg/d for 1 week, 500 mg/d for 1 week, and 500 mg BID for 10 weeks. Group 3 received simvastatin 10 mg/d plus niacin (375 mg for 1 week and 500 mg for 11 weeks). The lipid profile (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) and Lp(a) were measured before the start of therapy and at 6 and 12 weeks of treatment. Percentage changes from baseline were calculated. Adverse effects (AEs) were recorded at weeks 6 and 12 and through spontaneous reporting.

Results:

Ninety patients were enrolled (50 men, 40 women; 30 patients per treatment group). In group 1, the mean (SD) percentage decrease in LDL-C level at 12 weeks was 42.79% (16.29%) (P < 0.05), but no significant change was seen in group 2 or 3. The mean (SD) percentage increases in HDL-C level were 18.43% (13.28%) and 20.82% (17.57%) in groups 2 and 3, respectively (both, P < 0.05), but no significant change was seen in group 1. TC levels decreased by a mean (SD) of 32.97% (13.66%) in group 1 (P < 0.05), but no significant change was seen in group 2 or 3. TG and Lp(a) levels did not change significantly in any of the 3 treatment groups. Flushing, myalgia, and dyspepsia were the most common AEs in patients receiving niacin.

Conclusions:

In this study in Indian patients with dyslipidemia, simvastatin-niacin combination therapy was associated with greater changes in lipid profile compared with either agent used alone. Niacin was also associated with greater changes in Lp(a) levels. AEs were less prevalent with combination therapy than with niacin alone.Key words: dyslipidemia, simvastatin, niacin, combination therapy     

Abdominal pain as the initial and sole clinical presenting feature of systemic lupus erythematosus.

Classically, a diagnosis of systemic lupus erythematosus (SLE) is dependent on renal, rheumatological, cutaneous and neurological target organ damage with supporting serological markers. A previously healthy 26-year-old Japanese woman whose only manifestation of otherwise occult SLE was severe abdominal pain is reported. A computed tomographic scan of the abdomen revealed thickened loops of small bowel, endoscopic findings were nonspecific and jejunal biopsy revealed a nonspecific enteritis. Laboratory studies revealed lymphopenia, hypocomplementemia, a positive antinuclear antibody, a weakly positive anti-Smith and a strongly positive anti-double stranded DNA. There was a prompt symptomatic recovery with immunosuppressive therapy. The authors' experiences, and a review of the literature suggest that a diagnosis of SLE should be considered in young Asian women who present with significant but clinically enigmatic gastrointestinal illness.     

Mutational analysis of CACNA1G in idiopathic generalized epilepsy. Mutation in brief #962. Online

Recent studies have strongly implicated low voltage-activated/T-type calcium channels (T-channels) in the etiology of epilepsy. Here, we report the results of a mutational analysis of the CACNA1G gene, encoding the T-channel Ca(V)3.1/(1G) subunit, using a cohort of 123 mostly Japanese and Hispanic patients with idiopathic generalized epilepsies (IGE) and 360 healthy control individuals. We found 13 variants, including five which involved amino acid substitutions. One variant, c.1709C>T (Ala570Val), is present in a sporadic case of juvenile myoclonic epilepsy (JME) with early childhood absence and astatic seizures, but was not found in control samples. Another variant, c.3265G>T (Ala1089Ser), was observed in three family members affected with JME, and also in one control individual. Two JME patients and three control individuals harbored a third variant, c.2968G>A (Asp980Asn). Although not statistically significant, slightly faster inactivation decay rates were observed in some mutant channels. Our collective findings flag CACNA1G as a potential susceptibility locus for IGE subsyndromes that warrants closer investigation.     

冠状动脉搭桥患者围术期血浆15-F2t-isoprostane含量变化及临床意义

目的　分析常温心脏手术中血浆游离 15 F2 t isoprostane浓度变化及其与术后早期心功能的关系。方法　选择 30例在常温体外循环 (CPB)下行冠状动脉搭桥术患者 ,根据术后有 (组 )、无 (组 )应用正性肌力药物分为两组。 CPB中采用间断温血灌注 ,分别于麻醉诱导后、阻升主动脉后 30 min以及开放升主动脉后 10、30和 12 0 min抽取中心静脉血样 ,采用有高度特异性的兔血清抗体用酶标放射免疫法测量血浆中游离 15 F2 t isoprostane含量。术中至术后 6 h进行连续心排量测量。结果　 15 F2 t isoprostane血浆含量于阻升主动脉后 30 m in、开放升主动脉后 10 min显著升高 ,开放升主动脉 30 m in以后开始下降。组 患者血浆 15F2 t isoprostane含量的升高呈递减趋势 ,至开放升主动脉后 30 min恢复正常 ;相反 ,术后需两种以上正性肌力药物支持以维持心脏指数 (CI) >2 .2 L· m in- 1· m- 2的患者 (组 )血浆 15 F2 t isoprostane含量至开放升主动脉后 30 m in均显著高于正常。术后 CI与开放升主动脉后 10和 30 min时血浆游离 15 F2 t isoprostane含量呈良好的负相关性 (r=- 0 .95 ,P<0 .0 1)。结论　术中 15 F2 t isoprostane血浆含量与术后心功能的恢复密切相关。