Preformulation evaluation of AZD1305, an oxabispidine intended for oral and intravenous treatment.

Aim: AZD1305 is a novel, water-soluble investigational antiarrhythmic agent for restoration and maintenance of sinus rhythm in atrial fibrillation patients. The present studies were performed to evaluate the possibility for further development of the compound.

Methods: A set of technical approaches were used, including X-ray powder diffractometry, differential scanning calorimetry, thermogravimetrical analysis, dynamic vapor sorption, scanning electron microscopy, salt screen, and liquid chromatography.

Effects of probiotic fermented milk on symptoms and intestinal flora in patients with irritable bowel syndrome: a randomized, placebo-controlled trial.

Objective: The effect of probiotics on IBS symptoms has been mixed, but remains an intriguing treatment option with appeal to the patient.

Material And Methods: Patients fulfilling the Rome II criteria were randomized double-blind to a daily intake of 500 ml of fermented milk containing at least 5 × 10(7) CFU/ml of Lactobacillus paracasei ssp paracasei F19, Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12 or an equal volume of acidified milk for 8 weeks. Symptoms were assessed at baseline and weekly using a disease-specific validated symptom rating scale (IBS-SSI).

Clinical trial: the effects of a fermented milk containing three probiotic bacteria in patients with irritable bowel syndrome - a randomized, double-blind, controlled study.

Background: The effects of probiotic bacteria in IBS remain controversial.

Aim: To study the effects of a probiotic product on IBS symptoms.

Methods: We randomized 74 IBS patients to receive 8 weeks of daily treatment with 400 mL milk fermented with the yoghurt bacteria and containing Lactobacillus paracasei, ssp.

Callus formation and remodeling at titanium implants.

Titanium is biocompatible with bone tissue, and during the healing process bone makes intimate contact with the implant surface. Although much is known about the long-term healing of implants, less is known about the callus formation at implants. In this study, the histology of bone healing was studied during the period between 4 and 14 days.

Administration of Lactobacillus evokes coordinated changes in the intestinal expression profile of genes regulating energy homeostasis and immune phenotype in mice.

Lactic acid bacteria are probiotics widely used in functional food products, with a variety of beneficial effects reported. Recently, intense research has been carried out to provide insight into the mechanism of the action of probiotic bacteria. We have used gene array technology to map the pattern of changes in the global gene expression profile of the host caused by Lactobacillus administration.

Inhibitory effects of halothane on the thermogenic pathway in brown adipocytes: localization to adenylyl cyclase and mitochondrial fatty acid oxidation.

Volatile anesthetics such as halothane efficiently inhibit nonshivering thermogenesis as well as the cellular manifestation of that phenomenon: norepinephrine-induced respiration in brown adipocytes. To identify the molecular site(s) of action of such anesthetics, we have examined the effect of halothane on the sequential intracellular steps from the interaction of norepinephrine with isolated brown adipocytes to the stimulation of mitochondrial respiration (=thermogenesis). We did not identify an inhibition at the level of the adrenergic receptors, but a first site of inhibition was identified as the generation of cAMP by adenylyl cyclase; this led to inhibition of norepinephrine-induced expression of the uncoupling protein-1 (UCP1) gene and reduced norepinephrine-induced lipolysis as secondary effects.

Implantation of hydrophilic and hydrophobic titanium discs in rat tibia: cellular reactions on the surfaces during the first 3 weeks in bone.

In a previous study, a method for evaluation of short-time (1-8 days) healing of titanium implants in rat tibiae was described (J. Biomed. Mater.

Thermogenesis inhibition in brown adipocytes is a specific property of volatile anesthetics.

Background: This investigation examined the possibility that the inhibitory effect of halothane on nonshivering thermogenesis (heat production) in brown adipocytes is not a universal effect of all anesthetic agents but related to the type of anesthetic.

Methods: Brown adipocytes from hamster were isolated with a collagenase digestion method and incubated with anesthetic agents. The rate of oxygen consumption was measured with an oxygen electrode.

Life without UCP1: mitochondrial, cellular and organismal characteristics of the UCP1-ablated mice.

Mice devoid of the original uncoupling protein UCP1 have provided opportunities to delineate UCP1 function in a series of biochemical and physiological contexts. The isolated brown-fat mitochondria from such mice are fully coupled (without the addition of GDP), but still exhibit a depressed capacity for ATP synthesis. However, they only show a 2-fold decrease in sensitivity to the de-energizing effect of free fatty acids, compared with UCP1-containing mitochondria, whereas they possess a (UCP1-independent) 50-fold higher sensitivity than liver mitochondria; the fatty acid sensitivities in wild-type and UCP1-deficient mitochondria may, however, be of different natures.

Analysis of inhibition by H89 of UCP1 gene expression and thermogenesis indicates protein kinase A mediation of beta(3)-adrenergic signalling rather than beta(3)-adrenoceptor antagonism by H89.

Although it has generally been assumed that protein kinase A (PKA) is essential for brown adipose tissue function, this has not as yet been clearly demonstrated. H89, an inhibitor of PKA, was used here to inhibit PKA activity. In cell extracts, it was confirmed that norepinephrine stimulated PKA activity, which was abolished by H89 treatment.

Thermogenic responses in brown fat cells are fully UCP1-dependent. UCP2 or UCP3 do not substitute for UCP1 in adrenergically or fatty scid-induced thermogenesis.

To examine the thermogenic significance of the classical uncoupling protein-1 (UCP1), the thermogenic potential of brown adipocytes isolated from UCP1-ablated mice was investigated. Ucp1(-/-) cells had a basal metabolic rate identical to wild-type; the mitochondria within them were coupled to the same degree. The response to norepinephrine in wild-type cells was robust ( approximately 10-fold increase in thermogenesis); Ucp1(-/-) cells only responded approximately 3% of this.

Mechanistic differences of various AT1-receptor blockers in isolated vessels of different origin.

The functional inhibitory characteristics of the angiotensin II type 1 receptor blockers (ARB) candesartan; irbesartan; and losartan and its active metabolite EXP 3174 (EXP) were studied in rabbit aortic strips and rat portal vein preparations in vitro. Moreover, plasma-protein binding was determined, and the binding was high (>98. 5%) for all ARBs.

Analysis of the cellular mechanism for halothane inhibition of brown adipose tissue thermogenesis.

In the present studies, halothane is demonstrated to have a general inhibitory effect on norepinephrine-induced cAMP accumulation, lipolysis and rate of oxygen consumption, but no obvious effect on the respiratory capacity of isolated mitochondria. Further studies are necessary to elucidate these effects of halothane on brown adipose tissue nonshivering thermogenesis. Such studies may contribute to the understanding of the molecular effects of volatile anesthetics.

Halothane selectively inhibits nonshivering thermogenesis. Possible implications for thermoregulation during anesthesia of infants.

Background: During halothane anesthesia, infants fail to increase oxygen consumption in response to a cold stimulus in the form of an increase in temperature gradient between body and environment. Based on recent observations with isolated brown-fat cells, it seemed feasible that this inability to respond could be due to an inhibition of nonshivering thermogenesis during halothane anesthesia.

Methods: The rate of oxygen consumption was measured in cold-acclimated hamsters and rats.

Clinical evaluation of luteal function.

Objective: To determine the ability of luteal phase length determined by basal body temperature (BBT) pattern and a midluteal serum progesterone level to predict the result of an endometrial biopsy in a subsequent cycle.

Methods: We performed a retrospective analysis of 141 women with a history of infertility who were being evaluated for luteal function. The luteal phase length determined from a BBT chart of one menstrual cycle was compared to a single midluteal serum progesterone level from a second menstrual cycle.

Thermogenesis in brown adipocytes is inhibited by volatile anesthetic agents. A factor contributing to hypothermia in infants?

Background: In infants, nonshivering thermogenesis from brown adipose tissue provides an important source of heat for thermoregulation. Infants are known to have a high susceptibility to hypothermia during anesthesia. To investigate whether this could be due to an inhibition of nonshivering thermogenesis by anesthetics, the effect of preincubation with volatile anesthetics on the norepinephrine-induced heat production of brown adipocytes was investigated.

[Cesarean section under epidural anesthesia. A questionnaire study].

Seventy-four women selected at random who had been subjected to Caesarean section replied to questions about their satisfaction with epidural anaesthesia at various stages during the intervention. General discomfort increased during the intervention and pain contributed most to this. 96% of the women would recommend the method to others.

A microprocessor based feedback controller for mechanical ventilation.

A microcomputer feedback system has been developed which adjusts the inspired minute volume of a ventilator based on the patient's end-tidal CO2 concentration. The feedback controlled ventilator was evaluated in 6 dogs (18-20 kg). Arterial PCO2 was monitored continuously while end-tidal CO2 concentration was controlled by the micro-computer system and the following perturbations introduced: [1] NaHCO3 was infused IV, [2] a pulmonary artery was occluded, [3] one lumen of a double lumen endobronchial tube was occluded, and [4] an air embolism was given.

Microprocessors in intensive care medicine.

Three specific applications of microprocessors to intensive care instrumentation are presented. Automatic feedback control of mechanical ventilation is achieved using end-tidal carbon dioxide concentration, oxygen consumption, and carbon dioxide production as the input control parameters. Closed-loop control of fluid infusion is used for resuscitating burn patients; intravenous infusion rate is microprocessor controlled to maintain a desired urine output.