Choleretic activity of 2-demethoxycarbonyl-2-ethoxycarbonyl-11-deoxymisoprostol on the model of CCl<Subscript>4</Subscript>-induced hepatitis

Therapeutic administration of 11-deoxymisoprostol had a hepatoprotective effect, which manifested in a decrease in the content of alanine transaminase and aspartate transaminase in blood plasma, and produced a choleretic effect in rats with CCl₄-induced toxic hepatitis. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 2, pp. 183–184, February, 2008     

Synthesis and pharmacological properties of the 1-(furyl-2)-4-dimethylaminobutane and 1-(furyl-2)-5-dimethylaminopentane derivatives

Pharmaceutical Chemistry Journal -     

Bronchoscopy in complex examination and treatment of patients with lung abscess

Lung abscess was diagnosed during a complex examination in 115 patients. All the patients had local treatment through the bronchoscope. Cleansing of the abscess cavity takes place 1,3 times quicker in the patients who were given laser irradiation in addition to sanitation bronchoscopy or to whom immunomodulators and antibiotics were introduced lymphotropically intrabronchially, than in those with usual sanitation. The administration of 20 ml of glycerol in the abscess cavity allowed cleansing of the cavity to be 2-3 times quicker.     

Analysis of psychomotor activity in children with spastic infantile cerebral palsy by using the computer-assisted test system "Rhythmotest"

The paper considers how to obtain quantitative characteristics of sensomotor responses while tracing, learning, and reproducing rhythmical stimuli of different frequency and modality which can be used to assess psychomotor activity, perception, attention, short-term memory in schoolchildren with infantile cerebral paralysis. The results of examinations of children with this condition are given and analyzed.     

Peculiarities of maternal mortality in the University Hospital of Pleven for period 1977-2001

The authors report retrospective investigation of causes for maternal mortality in the Department of Obstetric and Gynecology in Hospital in Pleven for the period 1977-2001 and comparison between indexes for a different period of time. Objects of investigation were patient histories necropsy report and forensic expertise. Vital births were 73922 for a period of 25 years in Pleven. Dead pregnant and maternity were 45 and the rate of maternal mortality was 60,07/per 100 000 vital births. Causes of maternal mortality were divided in immediate 40 cases (88,88%) and indirect--5 cases (11,11%). The hemorrhage was the most common cause of maternal mortality--18 cases (45%). The authors mention that the absolute number of maternal losses is comparatively constant but the rate of maternal mortality in creases because of tendency of decrease of birthrate and concentration of pathology in Department of Obstetric and Gynecology in Pleven.     

A phase I evaluation of the effect of curcumin on dose‐limiting toxicity and pharmacokinetics of irinotecan in participants with solid tumors

Curcumin inhibits UDP‐glucuronyltransferases, a primary metabolic pathway for cancer chemotherapeutic agents like irinotecan. Concurrent administration of both agents may exacerbate irinotecan toxicity. We conducted this phase I study to determine the safety of concurrent curcumin and irinotecan administration. Ten participants with advanced solid tumors received one of four doses (1, 2, 3, and 4 g) of a curcumin phosphatidylcholine complex (PC) orally daily, and 200 mg/m² of i.v. infusion irinotecan on days 1 and 15 of a 28‐day cycle, to determine the maximum tolerated dose (MTD) of PC. Thirteen participants received 4 g of PC (MTD) to assess the effect on the pharmacokinetic (PK) properties of irinotecan and its metabolites, SN‐38 and SN‐38G. Irinotecan, SN‐38, and SN‐38G exposure equivalence with and without curcumin was assessed using area under the plasma concentration‐time curves from 0 to 6 h (AUC_0‐6h). Safety assessments and disease responses were also evaluated. The combination of irinotecan and PC was well‐tolerated. Because there was no dose limiting toxicity, the maximum dose administered (4 g) was defined as the recommended phase II dose of PC. PC did not significantly alter the plasma exposure and other PK properties of irinotecan and its metabolites. There was no apparent increase in the incidence of irinotecan‐associated toxicities. The objective response rate was 3/19 (22%, 95% confidence interval [CI]: 5–39%), median progression free survival and overall survival (n = 23) were 4 months (95% CI: 2.9–8.9 months) and 8.4 months (95% CI: 3.7 – not evaluable [NE]), respectively. Future studies are required to evaluate the efficacy of this combination.

Study Highlights

• WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Curcumin can be safely administered with some standard chemotherapy agents like gemcitabine, taxanes, and 5‐fluorouracil.

• WHAT QUESTION DID THIS STUDY ADDRESS?

Both curcumin and irinotecan are metabolized by UGT enzymes and concurrent administration may affect the pharmacokinetics (PKs) and clinical effect of irinotecan. This study sought to assess the effect of curcumin on the PK properties and adverse effect profile of irinotecan.

• WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?

Up to 4 g of a phosphatidylcholine curcumin (PC) formulation can be safely administered with irinotecan without an impact on the PK and adverse event profile of irinotecan.

• HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?

Curcumin’s anticancer properties have been documented. Higher doses of PC can be investigated to determine a dose that acts synergistically with irinotecan to improve clinical outcomes.     

Functional genomic screen of human stem cell differentiation reveals pathways involved in neurodevelopment and neurodegeneration

Human embryonic stem cells (hESCs) can be induced and differentiated to form a relatively homogeneous population of neuronal precursors in vitro. We have used this system to screen for genes necessary for neural lineage development by using a pooled human short hairpin RNA (shRNA) library screen and massively parallel sequencing. We confirmed known genes and identified several unpredicted genes with interrelated functions that were specifically required for the formation or survival of neuronal progenitor cells without interfering with the self-renewal capacity of undifferentiated hESCs. Among these are several genes that have been implicated in various neurodevelopmental disorders (i.e., brain malformations, mental retardation, and autism). Unexpectedly, a set of genes mutated in late-onset neurodegenerative disorders and with roles in the formation of RNA granules were also found to interfere with neuronal progenitor cell formation, suggesting their functional relevance in early neurogenesis. This study advances the feasibility and utility of using pooled shRNA libraries in combination with next-generation sequencing for a high-throughput, unbiased functional genomic screen. Our approach can also be used with patient-specific human-induced pluripotent stem cell-derived neural models to obtain unparalleled insights into developmental and degenerative processes in neurological or neuropsychiatric disorders with monogenic or complex inheritance.     

水体中克雷伯菌属的分布及其在水源性急性肠道感染中的价值

俄罗斯不同气候地区不同功能水体中克雷伯菌属广泛分布。克雷伯菌属可见于遭受生物、化学污染的集中供水的地表水源,无防护的地下蓄水层,缺乏有效清洁、消毒系统的饮用水。研究表明,水体中的克雷伯菌属具有致病性和毒性,对现代药物和消毒剂(氯、紫外线)具有抗性,很容易穿透进入地下蓄水层。克雷伯菌属细菌有很强的致病性(粘附力、侵袭力、磷酸酯酶、卵磷脂酶、脱氧核糖核酸酶、溶血活性),含有致病性遗传标记cnf-1。克雷伯菌属(100 CFU/dm³)可引起急性肠道感染。在不检测总大肠菌群的情况下,检测水体尤其是饮用水中的克雷伯菌属,可以评估所用水的流行病学危险。