Pharmacotherapeutic strategies for critical asthma syndrome: a look at the state of the art

ABSTRACT

Introduction

‘Critical Asthma Syndrome’ (CAS) is an umbrella term proposed to include several forms of asthma, responsible for acute and life-threatening exacerbations. CAS requires urgent and adequate supportive and pharmacological treatments to prevent serious outcomes.     

Design and synthesis of novel organometallic complexes using boronated phenylalanine derivatives as potential anticancer agents

Drug design and discovery studies are important because of the prevalence of diseases without available medical cures. New anticancer agents are particularly urgent because of the high mortality rate associated with cancer. A series of mononuclear gold (III) and platinum (II) complexes based on boronated phenylalanine (BPA) were designed and synthesized using 4,4’-dimethyl-2,2’-dipyridyl (L1) or 1,10-phenanthroline-5,6-dion (L2) ligands to obtain promising anticancer drug candidates. Proton nuclear magnetic resonance, infrared, mass spectrometry, and elemental analyses were utilized for chemical characterizations. Cell viability, cancer cell colony formation, endothelial tube formation, and cytoskeleton staining assays were performed using A549 lung adenocarcinoma and human umbilical vein endothelial cells (HUVECs) to investigate preliminary pharmacological activities. L1-based platinum (II) complex (BPA-L1-Pt) was the most promising complex, and has similar activity with the approved chemotherapy drug cis-platinum. Half maximal inhibitory concentration values for BPA-L1-Pt were 9.15 µM on A549s and 16.61 µM on HUVECs; the values for cis-platinum were 5.24 µM on A549s and 23.14 µM on HUVECs. Consequently, further synthesis studies should be performed to boost the cancer cell selectivity feature of BPA by varying metal and ligand types.     

NO-1886对高糖高脂饲料喂养新西兰兔糖代谢的影响

合成药NO-1886是脂蛋白脂肪酶(LPL)的激动剂，能降低血浆甘油三酯(TG)并升高高密度脂蛋白胆固醇(HDL-c)水平。我们曾发现NO-1886还具有降低血糖的作用。本研究主要观察NO-1886对糖尿病兔胰岛素抵抗及β-细胞功能方面的影响。用高糖高脂饲料诱导，使新西兰兔血浆葡萄糖升高，发生胰岛素抵抗。在高糖高脂饲料中添加1％NO-1886进行治疗。结果：发现NO-1886可抑制血清葡萄糖升高，经糖耐量和胰岛素敏感性试验检测，NO-1886可保护胰岛素的急性相分泌，增强胰岛素对葡萄糖的清除能力。研究结果提示NO-1886具有改善胰岛素抵抗、降低血糖的作用。     

Pharmacokinetic and -dynamic studies in elderlies with a potential antihypoxidotic/nootropic drug tenilsetam utilizing pharmaco-EEG and psychometry

In a double-blind, placebo-controlled study, the pharmacokinetic, encephalotropic, and psychotropic properties of a new metabolically active thienyl-piperazine derivative were studied in ten elderly subjects in their sixties by means of quantitative EEG and psychometric analyses. At weekly intervals, they received randomized single oral doses of placebo; 75 mg, 150 mg, and 300 mg tenilsetam (CAS 997); and 3.2 g piracetam as reference drug. Blood sampling EEG recordings, psychometric and psychophysiological tests, as well as the monitoring of blood pressure, heart rate, and side effects were carried out at 0, 2, 4, 6, 8, and 24 hr. Pharmacokinetic investigations showed that CAS 997 was rather well absorbed, as peak concentrations were observed consistently at 2 hr and were clearly dose-dependent. The terminal half-life was between 18 and 22 hr, as compared with 6 hr for the reference drug piracetam, which also exhibited plasma peaks at 2 hr. Computer-assisted spectral analyses of the EEG showed a significant CNS effect of CAS 997 as compared with placebo, characterized by an increase of alpha activity, decrease of delta activity, and fast beta activity, as well as by tendency towards an augmentation of total power and decrease of the centroid and centroid deviation of the total beta activity. Partly similar though less pronounced alterations were exhibited by 3.2 g piracetam. Such changes were described previously by us after several other antihypoxidotics/nootropics and are indicative of improvement in vigilance. Dose/treatment–efficacy calculations demonstrated 75 and 150 mg CAS 997 superior both to placebo and the reference compound but also to the highest given dosis (300 mg CAS 997). Time–efficacy calculations showed two pharrnacodynamic peaks: one in the 4th and another one in the 8th to 24th hour. The time lag between pharmacokinetic and -dynamic changes may be due to the penetration of the drug through the blood brain barrier to a deep compartment receptor as well as to the formation of active metabolites. Psychometric investigations showed only small and inconsistent psychotropic effects after single doses of CAS 997 in elderlies. Evaluation of pulse rate, blood pressure, and side effects showed a good tolerability of both drugs.     

Sulphanilic acid: divergent results in the guinea pig maximization test and the local lymph node assay

The guinea pig maximization test (GPMT) has proven to be a valuable tool for the identification of the skin sensitization potential of chemicals. The method identifies a hazard which can lead in the EC to compulsory labelling of that chemical. In the present study, data on sulphanilic acid derived from the GPMT has been compared with results from a second guinea pig assay (the cumulative contact enhancement test) and the murine local lymph node assay, both of which require only topical application of chemical. Except for the GPMT, no test identified any sensitizing activity associated with exposure to sulphanilic acid. These latter results are consistent with the experience gained from substantial human exposure in an occupational setting and from which no cases of allergic contact dermatitis to sulphanilic acid have arisen over a 20-year period. In consequence, it is questioned which test protocol in practice has given the more accurate identification of sensitization hazard relevant to man.     

Occupational irritant contact dermatitis and fungal infection in construction workers

We have examined 6 construction workers who developed chronic skin diseases on their hands over a period of 15 years (1970–1985). 4 developed a Trichophyton rubrum infection, and the other 2 an irritant contact dermatitis. All of them carried out jobs which caused traumatization of the skin, due to the presence of ethylene glycol and mineral oils during operation of pneumatic hammers in winter. They also suffered other types of skin trauma during their work. Construction workers may be at risk of developing an occupational skin disease involving fungal infection.     

A method for the accurate determination of anti-hapten cytotoxic T lymphocyte precursors: correction for apparent 'anti-self' reactivity

A method is described for accurately determining the frequency of precursors of hapten specific cytotoxic T cells. The method is based on a standard Poisson analysis of limit dilution cultures, but makes a correction of 'anti-self' reacting clones and for spontaneously arising clones that recognise modified self. These corrections are shown to be especially important when low hapten densities are used, where there may be more than a 10-fold difference between the corrected and uncorrected frequency estimates. Determined levels of antigen specificity and of H-2 restriction are significantly enhanced by application of this method.     

Developmental regulation of type 1 and type 3 interferon production and risk for infant infections and asthma development

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Computer assisted total knee arthroplasty: 2.5 years follow-up of 200 cases

IntroductionComputer assisted surgery in total knee arthroplasty (TKA) should improve accuracy of both femoral and tibial components placement. This study evaluated the functional outcomes of computer navigated total knee arthroplasty through the Knee Society Score (KSS) and Tegner Lysholm Knee Scoring Scale (TLKSS).Materials and methodsBetween September 2007 and February 2013, 180 patients (200 knees; 109 females and 71 males; mean age: 64 years) undergoing computer-assisted TKA were recruited. Plain radiographs and CT scans were performed post-operatively to evaluate alignment. The clinical outcomes were measured using the KSS and TLKSS pre-operatively and after 6, 12 and 36 months.ResultsThe mean follow-up duration was 2.5 years. The mean tourniquet time was 72 ± 13.4 min, and patients received an average of 0.6 ± 0.82 units of blood after surgery. The average preoperative KSS functional score of 44.6 ± 13.7 improved to 80.4 ± 16.4 after 2 years. The average preoperative TLKSS improved to 71.4 ± 13.5 after 2 years. The mechanical axis was within ±3° in all patients. No axial malalignments were observed on TC Scan. Three patients (1.6% of cases) required revision.ConclusionComputer assisted TKA allows reproducible alignment and kinematics, reducing outliers, provides ligament balancing and ensures good short term outcomes in terms of KSS functional score and TLKSS.