Evoked thalamic neuronal activity following DRG application of two nucleus pulposus derived cell populations: an experimental study in rats.

PURPOSE: To investigate the effects on evoked thalamic neuronal activity of application of notochordal cells and chondrocyte-like cells derived from nucleus pulposus (NP) onto a dorsal root ganglion (DRG) and to compare these effects with a previously reported increased thalamic activity induced by NP. METHODS: Nucleus pulposus was harvested from tail discs of adult rats and the disc cells were separated into two cell populations, notochordal cells and chondrocyte-like cells. The two cell populations were applied separately, or in combination, to the L4 DRG of anaesthetised female Sprague-Dawley rats during acute electrophysiological experiments. In control experiments, cell suspension medium was applied on the DRG. Recordings from the contralateral thalamus were sampled for 40 min while electrically stimulating the ipsilateral sciatic nerve at above Aδ-fibre thresholds. RESULTS: Application of notochordal cells resulted in a decrease in evoked thalamic activity within 10 min while chondrocyte-like cells did not induce any changes during the 40 min of recording. The difference in evoked thalamic activity 40 min after notochordal and chondrocyte-like cell application, respectively, was statistically significant. Neither an increased concentration of chondrocyte-like cells alone nor a combination of the two cell populations induced any changes in thalamic activity. CONCLUSIONS: Separate exposure of the DRG to the two NP-derived cell populations induced different effects on evoked thalamic activity, but none of the tested cell samples induced an increase in neuronal activity similar to that previously observed with NP. This indicates a high complexity of the interaction between NP and nervous tissue.

Effectiveness of ganciclovir against human herpesvirus-6 excreted in saliva in stem cell transplant recipients.

The aim of this study was to evaluate the effect of ganciclovir on human herpesvirus-6 (HHV)-6. Forty allogeneic stem cell transplant recipients were prospectively studied by repeated sampling of the saliva. The saliva samples were assayed for HHV-6 by quantitative polymerase chain reaction. HHV-6 was detected in 33 patients. Ganciclovir was given as preemptive therapy for cytomegalovirus infection during 15 episodes that were compared to 18 episodes without any concomitant antiviral therapy. The mean HHV-6 load decreased 0.49 (s.e. 0.31) log(10)/week in patients receiving ganciclovir whereas it increased 0.15 (s.e. 0.17) log(10)/week in episodes without antiviral therapy (P=0.04). We conclude that ganciclovir can decrease the HHV-6 viral load in saliva.

The STC-1 cells express functional orexin-A receptors coupled to CCK release.

Orexins are newly discovered neuropeptides regulating feeding and vigilance and have been detected in neuroendocrine cells of the gut. Potential neuroendocrine functions of orexin are unknown. Therefore, the effects of orexin-A on the intestinal neuroendocrine cell line, STC-1, were investigated as a model system. RT-PCR demonstrated the presence of both OX(1) and OX(2) receptors. Stimulation with orexin-A produced a dose-dependent release of cholecystokinin (CCK), which was abolished by removal of extracellular Ca(2+) or the presence of the voltage-gated L-type Ca(2+)-channel blocker diltiazem (10 microM). Orexin-A (Ox-A) elevated intracellular Ca(2+), which was dependent on extracellular Ca(2+). Furthermore, orexin-A caused a membrane depolarization in the STC-1 cells. Ox-A neither elevated cAMP levels nor stimulated phosphoinositide turnover in these cells. These data demonstrate a functional orexin receptor in the STC-1 cell line. Ox-A produces CCK release in these cells, by a mechanism involving membrane depolarization and subsequently activation of L-type voltage-gated Ca(2+)-channels.

Results of different strategies for reducing cytomegalovirus-associated mortality in allogeneic stem cell transplant recipients.

BACKGROUND: Several preventive strategies against cytomegalovirus (CMV) disease have been developed during the last decade. These have frequently been used in combination, and it has been difficult to identify each strategy's contribution. METHODS: Risk factors for CMV disease, death in CMV disease and transplant-related mortality were analyzed in 584 patients, who underwent a total of 594 allogeneic bone marrow transplants. RESULTS: The overall probability of CMV disease was 8.9%. No seronegative patient who had a seronegative marrow donor developed CMV disease. The corresponding probabilities for seronegative patients with seropositive donors, seropositive patients with seronegative donors, and seropositive patients with seropositive donors were 5.4%, 13.7%, and 11.7%, respectively. In multivariate Cox models, the use of preemptive antiviral therapy and being CMV-seronegative reduced the risk for CMV disease, CMV-associated death, and transplant-related mortality (TRM). Patients who received unrelated or mismatched family donor transplants had increased risks for CMV disease, CMV-associated death, and TRM. Older age was a significant risk factor for CMV disease and TRM. A total of 258 patients who were monitored by polymerase chain reaction for CMV DNA were analyzed separately to assess whether addition of another CMV preventive strategy could give benefit. Patients who received mismatched or unrelated donor transplants had increased risk for CMV disease, death in CMV disease, and TRM. High-dose acyclovir prophylaxis or addition of intravenous immune globulin had no influence. CONCLUSIONS: Preemptive therapy based on polymerase chain reaction for CMV DNA was associated with reduced risks for CMV disease, CMV-associated death, and TRM, whereas other prophylactic modalities did not give additional benefit.

Patients' conceptions of their life situation within the first week after a stroke event: a qualitative analysis.

The aim of this study was to find out how stroke patients conceived their life situation within the first week of the acute care phase as seen from the nurses' viewpoint. Six patients were interviewed within 3 weeks from their first stroke, using questions based on a holistic philosophy and analysed with the phenomonographic approach. Two main categories emerged from the results: the feeling of unreality and the awareness of a changed role in life, together with six subcategories; feeling of a changed perception of the body; feeling of being confused; loss of capability; awareness of confined life space; the importance of support and encouragement; and the will to look for new opportunities. The study concludes that the body change resulting from a stroke leads to both physical and psychological trauma, in which the psychological crisis can be very deep and best described as a personal catastrophe. The patient's capability to receive and understand information becomes blocked, which influences both the nurse and the patient's next of kin with regard to their care of the patient. Conversations with the patient must be frequent so that the acute care can be evaluated and agreement reached between the patient's wishes and the nurses' objectives. The results indicate the significance of intervention programmes based on crisis theory within the first week of a stroke event.

Comparison of the effect of the linseed extract Salinum and a methyl cellulose preparation on the symptoms of dry mouth.

The effect of a linseed extract Salinum and a sodium carboxymethyl cellulose preparation called MAS-84 was compared with regard to its effect on the symptoms of dry mouth. Twenty patients with xerostomia, who had been treated for cancer in the head and neck by radiation were recruited from the clinic for maxillofacial surgery, Malmo University Hospital. Following radiation treatment the salivation was severely reduced. The symptoms of a general feeling of a dry mouth, difficulties in chewing and swallowing, taste disturbances, problems with speech and mouth burning were registered on a subjective verbal rating scale. In addition plaque index and gingival bleeding were determined. The study design was crossover and performed single blind. The experimental period was 7 weeks. The patients were randomly divided into 2 groups. One group used Salinum and the other MAS-84 for 3 weeks. The fourth week was a wash out period and for the next three weeks the patients shifted preparation. Each of the preparations was used ad libitum. Registrations of the various parameters were undertaken on days 0, 7 and 21 of the respective period. At the initial examination all patients reported considerable disturbances from mouth-dryness. These symptoms were reduced in 15 patients during the Salinum period and in 9 during the MAS-84 period. The relief was significantly more pronounced during the use of Salinum compared to that during the use of the methyl cellulose preparation. On day 21 plaque and gingival bleeding were significantly reduced during the Salinum period but not during the MAS-84 period. The results of the present study confirm those of a previous pilot study and indicate that the linseed mucilage significantly reduced the symptoms of dry mouth. This effect increased with increasing time of saliva substitute use. The linseed mucilage Salinum appeared to be a suitable saliva replacement in mouth dry patients.

The effect of Salinum on the symptoms of dry mouth: a pilot study.

The effect of a new saliva substitute, Salinum, was tested in 37 patients with severe symptoms of reduced salivation. The majority of the patients had suffered from hyposalivation and dry mouth for more than 8 years. The saliva substitute consisted of a water soluble extract of linseed. The physical properties of this extract are similar to those of the glycoproteins of the salivary secretions. The patients used the saliva substitute for a seven days period. Prior to the use of the extract the patients reported that the most severe symptoms of decreased salivation were a feeling of dryness in the mouth and burning sensations in the tongue, pharynx and oesophagus, The majority of the patients reported that the use of Salinum reduced the symptoms of hyposalivation. Great variation in effect occurred from patient to patient. Generally the patients with the most severe symptoms experienced the greatest relief of the symptoms when they used Salinum. Although of short duration the results of this pilot study indicate that an extract of linseeds may compensate for some aspects of the consequences of reduced salivation. Further studies are needed to elucidate the feasibility of the extract as saliva replacement.

Green banana protection of gastric mucosa against experimentally induced injuries in rats. A multicomponent mechanism?

The protective capacities of fresh green (unripe) sweet bananas and of phosphatidylcholine and pectin (banana ingredients) against acute (ethanol- or indomethacin-induced) and chronic (indomethacin-induced) gastric mucosal lesions were evaluated in rats. Banana pulp was mixed with saline and given by gavage, as a pretreatment in a single dose. The identical protocol was used for pectin and phosphatidylcholine solution, and the dosages were adjusted to equal the amount of ingredients in the banana mixture, but higher concentrations were also given. The banana suspension reduced acute lesions, as did pectin and phosphatidylcholine in higher concentrations, but in concentrations as in fresh fruit no protective effects were observed except by pectin against indomethacin injury. In the model of chronic ulcers the banana suspension provided an incomplete and temporary protective effect. We conclude that the protective capacity of fresh green sweet bananas cannot be confined to only one active component. Pectin and phosphatidylcholine may protect gastric mucosa by strengthening the mucous-phospholipid layer, but the mechanism of protection afforded by bananas has to be further elucidated.

Formulation of a drug delivery system based on a mixture of monoglycerides and triglycerides for use in the treatment of periodontal disease.

This paper describes the development of a stable, controlled-release formulation of metronidazole for use in the treatment of periodontal disease. It is formulated as a suspension, which undergoes transformation to a release-controlling, semi-solid on contact with gingival fluid. The system is based on the ability of mixtures of monoglycerides and triglycerides to form liquid crystals, i.e., reversed hexagonals, in contact with water. The reversed hexagonal form was found to have the most favourable sustained release properties, compared with those from the cubic form. The source of metronidazole is the prodrug, metronidazole benzoate, which further helps to slow down the release rate. Product characteristics are assessed by differential scanning calorimetry and viscometry. The release data derive from the results of in vitro dissolution tests. X-ray diffraction, phase diagrams, and polarized light microscopy were used to elucidate the structure of the liquid crystalline phases.

Influence of beta-adrenergic receptor function during terbutaline treatment on allergen sensitivity and bronchodilator response to terbutaline in asthmatic subjects.

Nine asthmatic patients with an allergy to birch or timothy underwent bronchial allergen provocations on three different trial days, with intervals of 2 to 5 wk. Two weeks prior to one of the provocations, no medication was allowed. Before the other two provocations the patients had been on continuous treatment with oral terbutaline (7.5-mg slow-release pill bid) for 2 wk, which was discontinued 12 or 48 h before the allergen provocation. After allergen challenges, terbutaline was inhaled in increasing doses (0.5 mg, 1.0 mg, and 2.0 mg), and pulmonary function was measured after each dose. Before each allergen provocation, blood samples were drawn for measurements of catecholamine and terbutaline concentrations and for in vitro measurements of beta-adrenergic receptor function on lymphocytes (isoproterenol-induced accumulation of cyclic AMP). Beta-adrenergic receptor function on blood lymphocytes was impaired after the two treatment periods, compared with the drug-free period, and was significantly more depressed at 12 h than 48 h after dosing. The bronchial responsiveness to allergen, defined as PC20PEF (median values), was 1,700 biologic units (BU) after the period of no treatment and 220 BU and 445 BU at 12 and 48 h after discontinuation of the terbutaline treatment (p less than 0.1 after 48 h). Five of the nine patients exhibited increased bronchial responsiveness 48 h after treatment, compared to results without treatment. The responsiveness was similar on all occasions in three patients. The bronchodilator response to inhaled terbutaline after allergen-induced bronchoconstriction was attenuated (p less than 0.01) at both 12 and 48 h after terbutaline, compared to results without treatment, indicating desensitization also of the bronchial beta-adrenergic receptors. We conclude that the early bronchial responsiveness to allergen is increased following a period of continuous treatment with a beta-adrenergic receptor agonist in some asthmatic patients and that the capability of a beta-agonist to reverse allergen-induced bronchoconstriction is attenuated after beta-agonist treatment.

Structure of the starch granule--a curved crystal.

A structure model of the molecular arrangement in native starch proposed earlier is further considered, with special regard to the lateral packing of cluster units. The amylopectin molecules are radially distributed, with branches concentrated in clusters. Within each cluster the polyglucan chains form double helices which are hexagonally packed. The clusters form spherically concentric crystalline layers with amylose in an amorphous form acting as a space-filler. A translational mechanism for the change of helical direction at boundaries between clusters is proposed which can account for variations in the curvature of the concentric layers. The model is related to X-ray diffraction data and optical birefringence, considering dissembly at gelatinization. The structure is also discussed in relation to biosynthesis. Some aspects of gelatinization, such as the recent glass-transition approach, are then considered.

Characteristics of alveolar cells and soluble components in bronchoalveolar lavage fluid from non-smoking aluminium potroom workers.

Aluminium potroom workers have been reported to develop severe pneumoconiosis and bronchial hyperreactivity. The influence of inhalation of aluminium oxide and fluorides on the alveolar milieu was studied by bronchoalveolar lavage (BAL) in 14 male non-smoking potroom workers; 28 non-smoking healthy volunteers served as controls. The total numbers, concentrations, and proportions of various alveolar cells did not differ between the groups. The concentrations of albumin and fibronectin in BAL fluid were significantly higher (p less than 0.01 for both) in the exposed workers, reflecting an increased alveolar capillary permeability and an activation of alveolar macrophages (AMs). The concentration of angiotensin converting enzyme, another AM marker, was, however, decreased (p less than 0.01) in the workers. The concentration of hyaluronan, a fibroblast marker, did not differ between the groups. AMs from workers had a decreased capacity (p less than 0.05) to interact with yeast C3b particles but not to ingest them. The expression of HLA-DR and OKM1 on the cell surfaces of AMs were equal in the two groups. The BAL findings were not accompanied by restrictive lung disease in the workers. The fact that only a discrete alveolitis was found in the potroom workers may be due to a low grade of exposure to alumina and fluorides and to frequent use of respiratory protection equipment.

Lordosis behavior and GABAergic neurotransmission.

gamma-Aminobutyric acid (GABA) (1.0 microgram/cannula) or muscimol (50 ng/cannula) was injected into the ventromedial hypothalamus or the lateral septi nuclei of ovariectomized rats brought to sexual receptivity by combined treatment of estrogen and progesterone. No inhibitory effects of GABA or muscimol were observed on the lordosis behavior. Furthermore, systemic (1.0 mg/kg) or intrahypothalamic (50 ng/cannula) picrotoxin administration was followed by a statistically significant increase in lordosis behavior in ovariectomized, estrogen-primed rats. No such effect was observed in ovariectomized-adrenalectomized animals, indicating its dependence on adrenal secretions. Present results do not support the hypothesis of a GABAergic mechanism in the hormonal control of lordosis behavior.

Behavioral reactivity in spontaneously hypertensive rats.

Spontaneously hypertensive rats of the Okamoto strain (SHR) were compared with inbred normotensive rats of the Wistar-Kyoto strain (WKY) and with normally bred Wistar rats (NT) in tests on the audiogenic immobility reaction (freezing), open-field behavior in a dark and an enlightened arena respectively, auditory startle response and male sexual behavior. Compared to the WKYs the SHRs showed increased locomotion and rearing in the open-field situations, reduced startle response and shortened immobility reaction. The SHRs differed in the same way from the NT rats with the exception for motor activity in the dark arena, where no differences were observed. The WKY rats showed less motor activity than the NT animals. Both SH and WKY rats showed shorter latency time for ejaculation than the NT rats. The characteristics of the behavior patterns displayed by the SH rats were interpreted as indicating a reduced propensity for fear reactions in this strain of rats compared to the WKY and NT strains used in the present study.

The effect of medial preoptic-anterior hypothalamic lesions on testosterone plasma levels and testosterone conversion in the hypothalamus of male rats.

Male Wistar rats were submitted to bilateral high frequency lesions in the medial preoptic-anterior hypothalamic area or to sham procedure. The behavioral effect of the lesions was observed and plasma testosterone (T) and estradiol (E2) were measured by radioimmunoassay. In vitro metabolism of T was studied in the hypothalamus. Lesions produced a permanent deficit in male sexual behavior, an increase of plasma T and E2, and of hypothalamic T aromatization, and a decrease of T conversion to 5 alpha-dihydrotestosterone (DHT).

Effect of castration on hypothalamic testosterone metabolism in the male rat.

In vitro studies were performed of hypothalamic testosterone (T) metabolism 30 days after castration of adult male rats. No changes were seen in T conversion into dihydrotesterone and estrogens in the castrated rats. Plasma T levels were decreased while plasma estradiol concentrations did not differ from those of intact controls. It was suggested that the hypothalamic T metabolism probably is not androgen dependent.