In vitro study on the schedule-dependency of the interaction between pemetrexed, gemcitabine and irradiation in non-small cell lung cancer and head and neck cancer cells.

Background: Based on their different mechanisms of action, non-overlapping side effects and radiosensitising potential, combining the antimetabolites pemetrexed (multitargeted antifolate, MTA) and gemcitabine (2',2'-difluorodeoxycytidine, dFdC) with irradiation (RT) seems promising. This in vitro study, for the first time, presents the triple combination of MTA, dFdC and irradiation using various treatment schedules.

Methods: The cytotoxicity, radiosensitising potential and cell cycle effect of MTA were investigated in A549 (NSCLC) and CAL-27 (SCCHN) cells.

Counting clonogenic assays from normoxic and anoxic irradiation experiments manually or by using densitometric software.

The clonogenic assay is the method of choice to determine cell reproductive death after in vitro irradiation treatment. Traditionally, colony quantification has been performed by manual counting, a very laborious, time-consuming and rather subjective task. In this study, we compared manual counting by two skilled investigators with automated counting using the freely available ClonoCounter program.

The role of apoptotic cell death in the radiosensitising effect of gemcitabine.

Background: The aim of this study was to evaluate the radiosensitising effect of gemcitabine, in terms of cell-cycle progression, induction of apoptosis, and to investigate the molecular events regulating apoptosis.

Methods: Tumour cells were treated with gemcitabine, radiation, or the combination. 0-72 h after treatment, cells were collected for cell-cycle analysis and apoptosis determination.

Chemoradiation interactions under reduced oxygen conditions: Cellular characteristics of an in vitro model.

Hypoxic tumour regions often contain viable cells that are more resistant to chemotherapy and/or radiotherapy, making it of key importance to analyse new combination treatments under both normoxic and hypoxic conditions. In this study, the impact of moderate hypoxia and anoxia on cellular characteristics was investigated in isogenic A549 cells differing in p53 status. VEGF expression, doubling time, cell cycle distribution, induction of apoptosis and p53 protein expression were evaluated.

Development of a long-acting injectable formulation with nanoparticles of rilpivirine (TMC278) for HIV treatment.

Long-acting parenteral formulations of antiretrovirals could facilitate maintenance and prophylactic treatment in HIV. Using the poorly water- and oil-soluble non-nucleoside reverse transcriptase inhibitor (NNRTI) TMC278 (rilpivirine) as base or hydrochloride (HCl), nanosuspensions were prepared by wet milling (Elan NanoCrystal technology) in an aqueous carrier. Laser diffraction showed that the average particles size were (1) close to the targeted size proportionality (200-400-800 nm), with increasing distributions the larger the average particle size, and (2) were stable over 6 months.

[Surgical management of duodenal ulcer with hemorrhage from the gastroduodenal artery: antrectomy versus conservative surgery?].

When surgery is indicated for bleeding duodenal ulcer, the traditional standard of care has been "radical surgical treatment is preferable to conservative therapy since the risk of rebleeding is reduced without an augmentation in morbidity and mortality". This principle is based on two prospective studies published before 1995. Radical surgery at that time consisted of antrectomy, while conservative therapy included oversewing of the bleeding vessel in the ulcer bed and ligation of the gastroduodenal artery (Weinberg procedure).

Anti-inflammatory and cicatrizing activities of a carbohydrate fraction isolated from sugary kefir.

Kefir is an association of microrganisms generally grown in milk, with known probiotic activities identified from its soured suspensions. Aqueous media are also able to grow kefir, but little is known about the probiotic properties of its fermented products. This work aimed to evaluate some probiotic properties of a carbohydrate fraction isolated from sugary kefir (sugary kefir carbohydrate [SKC]).

[Not Available].

O. Brehant, D. Fuks, C.

Review: implications of in vitro research on the effect of radiotherapy and chemotherapy under hypoxic conditions.

As it is now well established that human solid tumors frequently contain a substantial fraction of cells that are hypoxic, more and more in vitro research is focusing on the impact of hypoxia on the outcome of radiotherapy and chemotherapy. Indeed, the efficacy of irradiation and many cytotoxic drugs relies on an adequate oxygen supply. Consequently, hypoxic regions in solid tumors often contain viable cells that are intrinsically more resistant to treatment with radiotherapy or chemotherapy.

Regiospecific synthesis of 4-alkoxy and 4-amino substituted 2-trifluoromethyl pyrroles.

A simple and regiospecific synthesis of 4-alkoxy(amino)-2-trifluoromethyl pyrroles from 5-azido-4-alkoxy(amino)-1,1,1-trifluoro-pent-3-en-2-ones by an aza-Wittig cyclization of aminophosphoranes is described. The structures of the pyrroles and their synthetic intermediates were supported by NMR and HRMS analysis.

The function debate in philosophy.

This paper reviews the debate on the notion of biological function and on functional explanation as this takes place in philosophy. It describes the different perspectives, issues, intuitions, theories and arguments that have emerged. The author shows that the debate has been too heavily influenced by the concerns of a naturalistic philosophy of mind and argues that in order to improve our understanding of biology the attention should be shifted from the study of intuitions to the study of the actual practice of biological inquiry.

Study of the effect of a liquid nutrition supplement on the nutritional status of psycho-geriatric nursing home patients.

Objectives: To evaluate the acceptance of a multinutrient liquid nutrition supplement in psycho-geriatric nursing home patients and the effect on weight, plasma nutrients and activities of daily life.

Design: Double-blind, placebo-controlled 12-week intervention study.

Setting: Two nursing homes in Boxtel, The Netherlands.

Stress responses to tilting and odor stimulus in preterm neonates after intrauterine conditions associated with chronic stress.

The effect of conditions linked with chronic intrauterine stress (CIUSTR) on the function of the autonomic nervous system (ANS) has not yet been evaluated systematically in premature neonates. We hypothesized that intrauterine stress deranges the function of the ANS as assessed by the clinical responses to certain stimuli. Twenty-one premature neonates who had suffered from CIUSTR, such as maternal smoking, maternal hypertension, and intrauterine growth retardation (STR Group), and 30 neonates who had not suffered from those intrauterine conditions were studied (C Group).

Stress responses in preterm neonates after normal and at-risk pregnancies.

Objective: To evaluate the autonomic response in preterm neonates born after an at-risk pregnancy.

Methodology: Twenty-one preterm neonates (gestational age; GA) 29-37 weeks; bodyweight (BW): 720-2113 g; postnatal age: 2-126 days), born after at-risk pregnancies (stressed (STR) group), were compared to 30 preterm neonates (GA: 26-36 weeks; BW: 813-2380 g: postnatal age: 2-86 days) without any intrauterine risk factor (C group). A 10 s pain stimulus was given on the forefoot and heart rate, respiratory rate and blood pressure were measured at 15 and 30 s, at 1, 2, 3, 4 and 5 min.

Clinical defense response to cold and noise in preterm neonates after intrauterine conditions associated with chronic stress.

Threatening stimuli may trigger abnormal reaction patterns in animals and infants. We investigated whether chronic intrauterine stress influenced these reactions. The autonomic defense response to cold and noise in 21 preterm newborns who had suffered from chronic intrauterine stress, such as maternal smoking, maternal hypertension, and intrauterine growth retardation (STR-group) was compared with the response in 30 preterm newborns without such condition (C-group).

Umbilical cord dopamine beta-hydroxylase, chromogranin A and met-enkephalin after conditions associated with chronic intrauterine stress.

Objective: To evaluate whether the markers of autonomic nervous system activity, dopamine beta-hydroxylase (DBH), chromogranin A (CGA) and met-enkephalin (E), are different in cord blood from neonates born after conditions associated with chronic intrauterine stress (CIUS) as compared to neonates born after a normal pregnancy.

Study Design: 61 newborns (median BW 2,840 g, range 617-4270 g) born after a pregnancy complicated by maternal hypertension, maternal smoking, maternal diabetes mellitus or intrauterine growth retardation (STR group) were compared with 88 neonates (median BW 2,910 g, range 4,00-4,370 g) who had not suffered from such intrauterine conditions. DBH, CGA and E were measured in the cord blood of both groups.

Cost recovery and improved drug availability in Niger--implications for total patient treatment costs.

Using quasi-experimental design methods, this study investigated, for a cost recovery intervention in Niger, how the total costs of an episode of treatment for an acute illness for a typical patient changed when user fees were imposed but accompanied by an improved drug supply. Episode costs included both cash and opportunity costs. With few exceptions, the comparisons of both the unadjusted and adjusted patient episode costs showed that patient total episode costs in the intervention sites increased relative to the control site.

Improving quality through cost recovery in Niger.

New evidence on the quality of health care from public services in Niger is discussed in terms of the relationships between quality, costs, cost-effectiveness and financing. Although structural attributes of quality appeared to improve with the pilot project in Niger, significant gaps in the implementation of diagnostic and treatment protocols were observed, particularly in monitoring vital signs, diagnostic examination and provider-patient communications. Quality improvements required significant investments in both fixed and variable costs; however, many of these costs were basic input requirements for operation.

In situ biodegradation of poly(3-hydroxybutyrate) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) in natural waters.

The biodegradation of samples of poly(3-hydroxybutyrate)(P(3HB)), poly(3-hydroxybutyrate-co-10%-3-hydroxyvalerate)(P(3HB-co-10 %-3HV)), and poly 3-hydroxybutyrate-co-20%-3-hydroxyvalerate)(P(3HB-co-20%- 3HV)) was investigated in situ in natural waters. The degradation was studied by decrease in mass, molecular weight, and tensile strength. In two freshwater ponds the polymers were slowly degraded.

Microbial degradation of poly(3-hydroxybutyrate) and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) in soils.

The microbial degradation of tensile test pieces made of poly(3-hydroxybutyrate) [P(3HB)] or a copolymer of 90% 3-hydroxybutyric acid and 10% 3-hydroxyvaleric acid was studied in soils incubated at a constant temperature of 15, 28, or 40 degrees C for up to 200 days. In addition, hydrolytic degradation in sterile buffer at temperatures ranging from 4 to 55 degrees C was monitored for 98 days. Degradation was measured through loss of weight (surface erosion), molecular weight, and mechanical strength.

The cost and efficiency of public and private health care facilities in Ogun State, Nigeria.

During the 1980s, Nigeria faced difficult economic conditions resulting in a severely constrained budget for public health services. To assess more carefully the costs and efficiency of the public and private health sectors, the Federal Ministry of Health in Nigeria undertook a comprehensive survey of health care facilities in Ogun State in 1987, the analysis of which is presented in this study. The findings suggest that there is potential to increase service delivery within existing budgets by more cost-effective allocation of inputs.

Biodegradation of polyhydroxyalkanoates.

Degradation of poly(3-hydroxybutyrate) and copolymers with 3-hydroxyvaleric acid was investigated in natural environments, and the microorganisms involved were isolated and identified. The influence of abiotic and biotic factors on the degradation is discussed.