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Biomedical subjects

A Kinnunen

Publications and source records attributed to A Kinnunen.

At least 19 recordsLinked to original sources
PubMed2005

Central nervous system drug development: an integrative biomarker approach toward individualized medicine.

Drug development for CNS disorders faces the same formidable hurdles as other therapeutic areas: escalating development costs; novel drug targets with unproven therapeutic potential; and health care systems and regulatory agencies demanding more compelling demonstrations of the value of new drug products. Extensive clinical testing remains the core of registration of new compounds; however, traditional clinical trial methods are falling short in overcoming these development hurdles. The most common CNS disorders targeted for drug treatment are chronic, slowly vitiating processes manifested by highly subjective and context dependent signs and symptoms. With the exception of a few rare familial degenerative disorders, they have ill-defined or undefined pathophysiology. Samples selected for treatment trials using clinical criteria are inevitably heterogeneous, and dependence on traditional endpoints results in early proof-of-concept trials being long and large, with very poor signal to noise. It is no wonder that pharmaceutical and biotechnology companies are looking to biomarkers as an integral part of decision-making process supported by new technologies such as genetics, genomics, proteomics, and imaging as a mean of rationalizing CNS drug development. The present review represent an effort to illustrate the integration of such technologies in drug development supporting the path of individualized medicine.

Animals↗
PubMed2004

Teaching public access defibrillation to lay volunteers--a professional health care provider is not a more effective instructor than a trained lay person.

BACKGROUND: Survival improves in witnessed out-of-hospital cardiac arrest if the victim receives bystander-initiated cardiopulmonary resuscitation and rapid defibrillation (BLS/AED). The European Resuscitation Council has a simple programme to teach these life-saving skills that require no previous experience of automated external defibrillators (AEDs). To be able to implement the use of AEDs widely, many instructors are needed, and therefore, lay persons may also be used as trainers. The purpose of this randomized study was to compare lay volunteers trained by a lay person with those trained by a health care professional using the Objective Structured Clinical Examination (OSCE). METHODS: Eight instructors, including four lay persons and four health care professionals, were given a basic course and an instructor course in CPR-D by the same instructor. All newly trained instructors trained 38 lay volunteers (19 pairs) who had no previous training in the use of a defibrillator. The lay volunteers performed the OSCE 2-3 weeks after the course. The OSCE comprised two scenarios with a manikin: the first, a patient in cardiac arrest with ventricular fibrillation, and the second, an imminent cardiac arrest with asystole as the initial rhythm. The same OSCE was performed by a group of lay first aiders practicing every 2 weeks who served as the control group. RESULTS: No statistical difference was present between the two groups of lay volunteers in the OSCE. All were able to use the AED and follow instructions. They identified patients with ventricular fibrillation and cardiac arrest, but had difficulties identifying cases with imminent cardiac arrest. The control group of trained first aiders performed significantly more effectively than the newly trained lay persons. CONCLUSIONS: No significant benefit exists in the trainer being a health care professional, but thorough training and subsequent rehearsing of the skills learned are crucial.

Cardiopulmonary Resuscitation↗
PubMed2003

Chlamydia trachomatis heat shock protein-60 induced interferon-gamma and interleukin-10 production in infertile women.

Chlamydia trachomatis-associated tubal factor infertility (TFI) involves enhanced humoral and cell-mediated immune response to the chlamydial 60 kDa heat shock protein (CHSP60). We evaluated the role of CHSP60-induced immune response in TFI by studying lymphocyte proliferation and cytokine (interferon (IFN)-gamma, interleukin (IL)-12 and IL-10) secretion in response to C. trachomatis elementary body (EB) and CHSP60 antigens in 57 women with TFI and in 76 women with other causes of infertility. Positive proliferative response of PBMC to CHSP60 was more common in the TFI group (20/57; 36%) than in the other groups (17/76; 22%) although the frequency or the median responses did not differ significantly (1.6, range 0.2-22.1 versus 1.4; 0.2-24.4). C. trachomatis EB induced significantly higher IFN-gamma and lower IL-10 secretion in the TFI group compared to the other groups. The EB and CHSP60 induced IL-12 secretion was similar in all study groups and correlated with IFN-gamma secretion in the other but not in the TFI group. The lack of correlation between EB-induced IL-12 and IFN-gamma production and simultaneously found prominent IL-10 secretion in response to CHSP60 in the TFI group suggests that the CHSP60 may have a specific role in regulating the immune reactions during chlamydial infection and may consequently contribute to the immunopathogenesis of TFI.

Adult↗
PubMed2000

Chlamydia trachomatis reactive T lymphocytes from upper genital tract tissue specimens.

Chlamydia trachomatis infection is associated with pelvic inflammatory disease (PID) and tubal factor infertility (TFI). We investigated the role of C. trachomatis as a target antigen of endometrial and salpingeal tissue lymphocytes derived from PID and TFI patients. Antigen specificity of the tissue originated T lymphocyte lines (TLL) was tested against C. trachomatis elementary bodies and chlamydial heat shock protein 60 (CHSP60). C. trachomatis antigen stimulated proliferation in two out of eight endometrial TLL derived from PID patients and three out of four TLL derived from TFI patients. All (n = 4) TLL derived from the salpingeal specimens responded to CHSP60 compared with only one out of 12 TLL derived from the endometrial specimens. In-vivo expression of interferon-gamma (IFN-gamma) mRNA revealed that it was present in nine of 13 specimens obtained from PID patients. The dominant activity of type-1 T lymphocytes was confirmed by the in-vitro production of IFN-gamma (median 1007 pg/ml) from all (n = 5) C. trachomatis specific TLL while IL-5 secretion was lower (median 779 pg/ml). In conclusion, C. trachomatis reactive TLL were established from in-vivo activated lymphocytes from the upper genital tract tissue of PID and TFI patients. The reactivity of the salpingeal TLL to CHSP60 provided further evidence that immunoreactivity to CHSP60 is a predominant response in patients with tubal damage.

Adolescent↗
PubMed2000

Safety evaluation of sous vide-processed products with respect to nonproteolytic Clostridium botulinum by use of challenge studies and predictive microbiological models.

Sixteen different types of sous vide-processed products were evaluated for safety with respect to nonproteolytic group II Clostridium botulinum by using challenge tests with low (2. 0-log-CFU/kg) and high (5.3-log-CFU/kg) inocula and two currently available predictive microbiological models, Food MicroModel (FMM) and Pathogen Modeling Program (PMP). After thermal processing, the products were stored at 4 and 8 degrees C and examined for the presence of botulinal spores and neurotoxin on the sell-by date and 7 days after the sell-by date. Most of the thermal processes were found to be inadequate for eliminating spores, even in low-inoculum samples. Only 2 of the 16 products were found to be negative for botulinal spores and neurotoxin at both sampling times. Two products at the high inoculum level showed toxigenesis during storage at 8 degrees C, one of them at the sell-by date. The predictions generated by both the FMM thermal death model and the FMM and PMP growth models were found to be inconsistent with the observed results in a majority of the challenges. The inaccurate predictions were caused by the limited number and range of the controlling factors in the models. Based on this study, it was concluded that the safety of sous vide products needs to be carefully evaluated product by product. Time-temperature combinations used in thermal treatments should be reevaluated to increase the efficiency of processing, and the use of additional antibotulinal hurdles, such as biopreservatives, should be assessed.

Botulinum Toxins↗
PubMed1999

Predicted and observed growth and toxigenesis by Clostridium botulinum type E in vacuum-packaged fishery product challenge tests.

The observed growth and toxigenesis by Clostridium botulinum type E in vacuum-packaged unprocessed, raw pickled and cold-smoked rainbow trout stored at slightly abusive temperatures were compared to predictions generated by two currently available predictive microbiological programs, Food MicroModel and Pathogen Modelling Program. In unprocessed fish there was only a 2 log increase in type E cell count at the time the toxicity first occurred after 2 weeks storage at 8 degrees C. Neither growth or toxin production was observed in raw pickled fish with a NaCl concentration of 6.7% (w/v) during 6 weeks storage at 6 degrees C. In cold-smoked fish with a NaCl level of 3.2% (w/v) toxic samples were detected after 3 and 4 weeks storage at 8 degrees C and 4 degrees C, respectively, without any increase in type E count. Both models were hampered by limitations to controlling environmental factors set by the programs which also had an adverse effect on the reliability of predictions. Most predictions generated by the models were inconsistent with the results observed in the challenge studies. In certain situations, the models seemed to be 'fail-safe', in that, the growth rate predicted from the model was faster or a predicted time to toxicity shorter than that which actually occurred in the food. In other situations, the predictions showed the product to be safe when it was not. The results demonstrate the need for further development and rigorous validation of the models before they are accepted for wider use by inspecting officials and the food industry.

Animals↗
PubMed1999

Heparan sulphate and HB-GAM (heparin-binding growth-associated molecule) in the development of the thalamocortical pathway of rat brain.

Extracellular matrix (ECM) molecules, such as laminin, tenascin, chondroitin sulphate proteoglycans and heparan sulphate proteoglycans have been suggested to have 'signpost' and directing roles in the formation of axonal projections in cortical development. We show here that the expression of the neurite outgrowth-promoting protein heparin-binding growth-associated molecule (HB-GAM) and N-syndecan, a transmembrane heparan sulphate proteoglycan previously isolated as a receptor for HB-GAM, is spatiotemporally associated with the developing thalamocortical pathway in the rat brain. Using in situ hybridization, thalamic neurons were shown to express mRNA for N-syndecan, and in vitro, thalamic neurons grew more neurites on HB-GAM than on laminin. The HB-GAM-induced neurite outgrowth in thalamic neurons was inhibited by heparitinase, heparin, soluble N-syndecan and by an excess of soluble HB-GAM in the culture medium. In a pathway assay, thalamic neurons selectively preferred attaching and growing neurites on matrices containing HB-GAM than on those containing fibronectin or laminin alone, suggesting that HB-GAM may modulate the effect of other ECM proteins. On an unfixed brain slice preparation, thalamic neurons repeatedly showed a typical neurite outgrowth and attachment pattern resembling the expression pattern of HB-GAM. On the brain slices, the neurite outgrowth was significantly inhibited by heparitinase, heparin and soluble HB-GAM, thus displaying features of neurite outgrowth on matrix-bound HB-GAM. Our results suggest that HB-GAM is important for the neurite outgrowth of thalamic neurons and it may function as an ECM-bound guidance cue for thalamic neurons that possess HB-GAM-binding heparan sulphates on their cell membrane.

Animals↗
PubMed1999

Recent trends in drug treatment in Europe.

The article describes the recent developments in drug treatment systems in several European countries. The article is based on the up-dated papers delivered in the closing meeting of the ISDRUTS-project (International Study of the Drug Treatment Systems) in Lisbon, October 7-9, 1998. In the article latest trends in drug situation and drug-related harm in different countries are represented. Also recent changes in legal measures, the proceeding of the harm reduction measures, the situation with heroin trials, the implosion of the drug treatment system into the alcohol treatment system and alternatives to imprisonment and other diversion mechanisms for addicts are described. In the concluding chapter recent trends in drug treatment are analysed in the framework of the political climate in Europe.

Crime↗
PubMed1999

The storage life of packed shredded Iceberg lettuce dipped in glycine betaine solutions.

The effects of glycine betaine dip, packaging method, and storage time on the sensory quality of shredded Iceberg lettuce were first modeled using a statistical experimental design, followed by a second storage test verifying the effect of the glycine betaine treatment. Shredded lettuce was dipped in 0 to 100 mg/liter active chlorine solution and then in 0 to 1.0 mol/liter glycine betaine solution, packed in 25 microm oriented polypropylene film, 250 g per package, and stored at 5 degrees C for 8 days. Models with good predictability were created suggesting that the glycine betaine dip helped retain sensory quality, especially appearance (P < 0.05). The models also suggested that washing periods over 60 s were not needed and that the microperforation of packages should not exceed 0.31 mm2 per package. The modeled positive effect on sensory quality was verified in the second storage test (P < 0.05). The optimum glycine betaine concentration was 0.2 mol/liter. Chlorination of the first dip particularly retained appearance of packed lettuce.

Betaine↗
PubMed1998

In situ detection of H1-receptor mRNA and absence of apoptosis in the transient histamine system of the embryonic rat brain.

In the developing brain, histamine is one of the first neurotransmitters to appear. The concentration of histamine in the prenatal brain is fivefold that of adult levels. During the prenatal development a large transiently histamine-immunoreactive cell population distinct from the adult histaminergic system can be found within a subpopulation of the developing serotonergic raphe nuclei neurons. Also histamine-immunoreactive nerve fibers are widely distributed already during the prenatal development extending to the diencephalon, the thalamus, the cortex, and the spinal cord. Large numbers of histamine-containing mast cells also migrate into the brain during the late prenatal life. The wide distribution and high prenatal concentrations imply important functions for the histaminergic system during intrauterine development. However, little is known about the actual functions of histamine during development, and which of the histamine receptors are present in the prenatal rat brain is currently unknown. In the present study, we used in situ hybridization to study the distribution of H1-receptor (H1R) mRNA in the embryonic rat brain and spinal cord. H1R mRNA could be detected in rat brain and in spinal cord on embryonic day (E) 14, and the expression pattern seemed to partially localize in areas containing histamine-immunoreactive nerve fibers through E14-E20. H1R mRNA was also detected by reverse transcriptase polymerase chain reaction from embryonic brain samples and by Northern hybridization. The possible involvement of apoptosis in the disappearance of the developing transiently histaminergic system was studied by using apoptosis detection based on the terminal dUTP nick end labeling (TUNEL) technique and with c-Fos immunostaining. Although histamine immunoreactivity disappears dramatically from the developing raphe nuclei after E18, only occasional apoptotic nuclei could be seen in the histamine-immunoreactive cell bodies. The presence of H1R mRNA during the embryonic development renders it possible that histamine could exert an H1R-specific function at the time of the embryonic histamine peak.

Animals↗
PubMed1998

N-syndecan and HB-GAM (heparin-binding growth-associated molecule) associate with early axonal tracts in the rat brain.

Heparin-Binding Growth-Associated Molecule (HB-GAM)/pleiotrophin is an 18 kDa extracellular matrix- and cell-surface-associated protein shown to enhance neurite outgrowth of perinatal forebrain neurones in vitro. The heparan sulphate proteoglycan N-syndecan (Raulo et al., 1994) has been isolated as a receptor/coreceptor for the HB-GAM. We have investigated, whether HB-GAM and N-syndecan could have a similar role in neurite outgrowth and axon guidance in early axonal tracts of brain. In the present study N-syndecan was found to be spatiotemporally associated with the developing axonal tracts already on embryonic day 9 in rat, as revealed by coexpression with class III beta-tubulin, which is one of the earliest neuronal markers (Easter et al., 1993; Brittis et al., 1995). Later, N-syndecan and HB-GAM were detected in the first afferent serotonergic projections arising from the pontine raphe nuclei. The expression pattern of HB-GAM peaked in the developing rhombencephalon at embryonic stage (E) 13-14. At the same time, N-syndecan was expressed in the developing raphe neurones growing neurites towards the diencephalon along HB-GAM immunoreactive pathways. When rhombencephalic neurones were cultured on decreasing concentrations of substrate-bound HB-GAM, E13 neurones showed a significantly better neurite outgrowth response than E11, E16 or E18 neurones. The neurite outgrowth of raphe neurones in vitro was inhibited by adding soluble heparin or N-syndecan into the culture medium, whereas addition of chondroitin sulphate had no effect. In a simple pathway assay, E13 raphe neurones selectively preferred attaching and growing neurites on pathways containing HB-GAM as compared with regions containing either laminin or fibronectin alone. Our results suggest that HB-GAM may function as a developmentally regulated cue for rhombencephalic neurones that possess N-syndecan on their cell membrane.

Animals↗
PubMed1993

Histamine: its metabolism and localization in mammary gland.

1. Mammary gland of mouse (Mus musculus), rat (Rattus rattus), guinea pig (Cavia porcellus), cow (Bos taurus) and pig (Sus scrofa) contains different but always high concentrations of histamine. 2. Generally, the tissue histamine is localized in mast cells, although non-mast cell histamine immunoreactivity is also present in mammary glands of the mouse, cow and pig. No histamine immunoreactive nerves could be detected. 3. Mammary glands are able to synthesize and inactivate histamine; the activity of specific histidine decarboxylase and at least one of the catabolizing enzyme could be demonstrated. 4. Histamine fulfils basic criteria for being involved in physiological function of mammary glands.

Animals↗
PubMed1991

Histamine and tyrosine hydroxylase in developing rat brain.

The distribution of histamine and tyrosine hydroxylase in fetal rat brain was investigated immunocytochemically in order to determine possible colocalization of these two substances. Embryonic rat brains were fixed with carbodiimide and processed for immunofluorescence studies with antisera against histamine and tyrosine hydroxylase either in the same sections or in consecutive sections. Histamine and tyrosine hydroxylase showed no colocalisation in the developing rat brain. However, fibre networks immunoreactive for histamine and tyrosine hydroxylase were often found in the same areas. The results of the study suggest that the catecholaminergic and histaminergic neurones develop separately in the rat brain. Based on the location of developing histamine-immunoreactive neurones, a more intimate relationship between histamine- and serotonin-containing neurones in the developing rat brain is plausible.

Animals↗
PubMed1990

Nimodipine after resuscitation from out-of-hospital ventricular fibrillation. A placebo-controlled, double-blind, randomized trial.

One hundred fifty-five consecutive patients resuscitated after out-of-hospital ventricular fibrillation by a physician-manned advanced life support unit were randomly assigned to receive nimodipine or placebo at a dosage of 10 micrograms/kg as an intravenous injection immediately after restoration of spontaneous circulation, followed by an infusion of 0.5 micrograms/kg per minute for 24 hours. No significant difference was found in the 1-year survival rate of nimodipine-treated (30 [40%] of 75 patients) and placebo-treated patients (29 [36%] of 80 patients). Recurrent ventricular fibrillation during the treatment occurred in one patient in the nimodipine group compared with 12 patients in the placebo group. In a post hoc analysis of patients with very long delays in advanced life support (more than 10 minutes), the 1-year survival rate was higher with nimodipine (eight [47%] of 17 patients) than with placebo (two [8%] of 26 patients). Nimodipine may be of benefit in patients with delayed resuscitation.

Aged↗