Intrathecal bradykinin administration: opposite effects on nociceptive transmission

Injected intrathecally, bradykinin (BK) produced either hyperalgesia (0.15 microg) or antinociception (6.0 microg) in rats when thermal noxious stimuli were used. Similarly, des-Arg(9)-BK at the lower dose (0.15 microg) decreased, whereas at the higher dose (6.0 microg) it increased the threshold to thermal noxious stimuli; however, these effects were less pronounced than those of BK. The antinociception induced by BK was abolished by HOE 140, a B(2) receptor antagonist, injected intrathecally at a dose of 1.3 ng and was markedly attenuated by des-Arg(10)-HOE 140, a B(1) receptor antagonist (1.15 ng i.t.). The results obtained in this study showed that--depending on the dose used--BK and des-Arg(9)-BK could produce pro- as well as antinociceptive actions. Both B(2) and B(1) receptors are involved in the action of intrathecally applied BK.     

Nutrients intake of the adolescents in Poland--ten years literature review (1990-2000)

The dietary survey among adolescents (11-15 years old) performed during last decade in Poland are not representative for national level. The analysis of data obtained by 24-h recall in different regions showed that contribution of dietary fat to energy intake was too high (37-42%), while contribution of proteins (10-11%) and carbohydrates (47-52%) too low. The intake of proteins, fibre, calcium, magnesium, copper and iron (especially among girls), vitamin C and niacin did not meet the recommended levels. The results suggest that girls are more likely to have risk of nutritional deficiencies than boys as well as adolescents from rural area than from towns. Inadequate intake of nutrients during adolescence can increase risk of dietary related diseases in later life.     

Transplants as a therapy after spinal cord injury

This review describes shortly phenomena that take place in different parts of central nervous system (CNS) after the spinal cord injury: 1/ due to axotomy many of neurones present outside the cavity of lesion (even those of supraspinal origin) can atrophy or die as an effect of necrosis or apoptosis; 2/ at the injury site itself, the primary and secondary effects lead to increased cell loss and the scar or cyst formation that are the mechanical barrier for regenerating axons; 3/ due to abolished conduction across the injury site the spinal cord circuitry below the lesion is deprived of supraspinal inputs. Then this review presents the new therapeutic strategies that were developed recently to obtain at least partial recovery of motor functions after spinal cord injury. The cell body can be rescued by applying various factors that increase intrinsic neural repair (e.g. neurotrophins or anti-apoptotic agents). To enhance the axonal regrowth through the lesion cavity, the scar and cyst formation can be reduced by constructing the bridges using e.g. the Schwann cells, fetal tissue, stem cells, olfactory ensheating glial cells, or by application of macrophages. To induce partial restoration of some functions that are controlled by neural circuitry below the lesion the various methods for enhancing the plasticity in segmental circuitry were developed (e.g. rehabilitation by locomotor training or intraspinal transplantation of monoaminergic cells). As a consequence of the great unpredictability of effects obtained after injury at different parts of the spinal cord the various strategies for repair need to be coordinated for optimal recovery.     

Die Eignung von trypsiniertem Nagelkeratinstaub, Stratumcorneum-Partikeln oder Glutamat als Kohlenstoff-Stickstoff-Quellen für Trichophyton mentagrophytes und Trichophyton rubrum

• 1 Im Rahmen vergleichender Untersuchungen zum Keratinabbau durch Dermatophyten wird über Wachstum, Stoffwechsel, physiologische Prinzipien und Intensität der Keratinolyse, die Ausscheidung von Enzymen und das Verhalten in der autolytischen Phase unter Verwendung von trypsiniertem Nagelkeratinstaub, Stratum-corneum-Partikeln und Glutamat als C-N-Quellen berichtet.
• 2 Schonende Trypsinierung (0,01 % Trypsin; 0,043 M Phosphatpuffer; pH 8,0) führt bei Nagelkeratinstaub, der eine große relative Oberfläche besitzt, innerhalb von 5 Tagen bei 23° C zu Gewichtsverlusten von 23 bis 35 %. Von Stratum-corneum-Partikeln werden unter gleichen Bedingungen bei geringer relativer Oberfläche 84 % zu löslichen Oligo- und Monomeren abgebaut.
• 3 Dermatophyten (Trichophyton mentagrophytes, Tr. rubrum) können trypsinierten Nagelkeratinstaub als vollwertige C-N-Quelle nutzen und erzielen dabel einen Keratinabbau von 80 bis 90 %. Die Geschwindigkeit der Keratinolyse; nicht aber ihr endlich erreichtes Ausmaß, werden durch den Trypsinierungsgrad negativ, durch die relative Oberfläche der Keratinpartikel positiv beeinflußt.
• 4 Ein wichtiges physiologisches Prinzip der mikrobiellen Keratinolyse ist neben dem poteniellen Sulfitmechanismus die aktive Alkalisierung des Substrates (Terrains). Sie erfolgt seitens der Pilze durch Ammoniaksekretion nach intracellulärer oxydativer Desaminierung und durch Ammoniakfreisetzung mittels extracellulärer Säureamidspaltung (Asparaginase).
• 5 Stratum-corneum-Partikel, die nach den Ergebnissen der Trypsinierungsversuche reichlich Nichtkeratinproteine und in geringeren Mengen Präkeratine bzw. trypsinlabile Keratine enthalten, werden als C-N, Quelle von Tr. mentagrophytes in kurzer Zeit praktisch vollständig und zwar ebenso schnell wie, wenn nicht sogar schneller als, Glutamat umgesetzt. Stratum corneum ist demnach als “ideale” Nährstoffquelle für Dermatophyten zu bewerten.
• 6 Das “Keratinase-Problem” wird eingehend diskutiert und dahingehend beantwortet. daß es unseres Erachtens keine streng keratinspezifischen Proteinasen bei Hautpilzen gibt, wohl aber im Komplex der keratinolytischen Prinzipien proteolytische Enzyme, die an die beim Keratinabbau vorliegenden komplizierten Bedingungen angepaßt sind, d. h. relativ hohe Sulfit-, Sulfat-, Ammoniaktiter und entsprechende pH-Werte tolerieren.
• 7 Obwohl in der autolytischen Phase Verluste an Biomasse bis zu 40 % der Myzelhöchstgewichte eintreten, so bleiben doch — jedenfalls in vitro; und warum sollte es in vivo prinzipiell anders sein (?) — über lange Zeit (mit Glutamat mindestens 140 Tage) Thallussegmente vital und ektoenzymatisch aktiv. Diese Befähigung zum langdauernden Überleben wird als Merkmal mit positivem Selektionswert beurteilt.

     

Serotonin-related enhancement of recovery of hind limb motor functions in spinal rats after grafting of embryonic raphe nuclei

Recently, we demonstrated improvements in hind limb locomotor-like movements following grafting of embryonic raphe nuclei cells into the spinal cord below the level of total transection in adult rats. The purpose of the present study was to clarify whether this improvement was due to newly established serotonergic innervation between the graft and the host. Two months after intraspinal grafting of the embryonic raphe nuclei, the spinalized rats, when put on a treadmill, could be induced to walk with regular alternating hind limb movements with the plantar contact with the ground during the stance phase, and ankle dorsiflexion during the swing phase of each step cycle. In the same situation the spinal rats, that did not receive the graft, were not able to initiate the dorsiflexion of the ankle joint during the swing phase and very often the dorsal surface of the foot was dragged along the ground. Intraperitoneal application of directly acting 5-HT2 antagonist Cyproheptadine (1 mg/kg) impaired reversibly the hind limb locomotor-like movements in grafted rats. This impairment lasted for 2-3 h. The same procedure in control rats did not markedly alter the hind limb locomotor-like movements. The effect of Cyproheptadine in grafted rats was reversed by i.p. injections of the 5-HT2 agonist Quipazine (0.5 mg/kg). These results show that the graft-induced restitution of hind limb locomotor abilities in adult spinal rats is brought about by the new serotonergic innervation of the host spinal cord circuitry from the grafted neurons and is mediated by 5-HT2 receptors.     

Experimental intraprostatic injection of bacillus Calmette-Guerin: a feasibility and safety study

PURPOSE: We investigated the feasibility and safety of intraprostatic administration of bacillus Calmette-Guerin (BCG) and determined the histological changes induced by this approach. MATERIALS AND METHODS: A total of 36 healthy male beagle dogs 2.2 to 3.6 years old weighing 10.0 to 14.8 kg were randomly assigned to 6 experimental groups. Four groups were given intradermal BCG vaccination and 6 weeks later they were given 0 (group 1), 10 (group 2), 5 x 10 (group 3) or 10 (group 4) BCG organisms intraprostatically. An additional group received prevaccination, followed 6 weeks later by a dose of 10 BCG organisms intraprostatically and then 6 weeks of antibiotics (group 5). Another group receiving no prevaccination and 5 x 10 BCG organisms intraprostatically at week 6 were included (group 6). RESULTS: Adverse reactions (ARs) were seen in 12 dogs, including inguinal lymphadenopathy in 3, an anal lesion in 5, constipation in 7 and dysuria in 3. There was a trend toward an increased incidence of ARs in high dose groups 3 and 4, fewer ARs in group 5 and no ARs in group 6. There was minimal evidence of systemic dissemination of BCG in any group. Post-necropsy histological analysis indicated higher inflammation as well as glandular destruction in high dose groups 3 and 4. Antibiotics did not seem to lessen the histological response to intraprostatic BCG injection (group 5). Interestingly in nonvaccinated group 6 the level of inflammation as well as glandular destruction was higher. CONCLUSIONS: Our results indicate that intraprostatic BCG administration in dogs is a safe and well tolerated procedure. It is free of major or long lasting serious complications.     

Quantitative assessment of mRNA TGF-beta1 in liver tissue in connection with serum mean daily level of TGF-1 in chronic hepatitis B patient

Monitoring of fibrosis process with the use of histopathologic studies on liver's bioptates is limited, so it is attempted to find reliable, obtained with less invasive methods, sensitive and reflecting fibrosis dynamics markers of this process. The aim of the study was simultaneously to assess liver's expression as well as circadian and mean daily TGF-betal concentration in serum of patients with chronic hepatitis type B in comparison to control group. Studies were performed on 50 patients (9 women, 41 men) aged 45.9 +/- 2.3 years with chronic hepatitis type B. Control group consisted of 20 patients (mean age 38.6 +/- 3.7 years), in which so called minimal changes without fibrosis were observed in histophatologic bioptate of liver. Blood for studies was collected every 4 houres during the day. Serum concentration of TGF-betal was assessed with the use of ELISA method, and expression of mRNA TGF-betal in liver with QRT-PCR method. No significant difference between circadian as well as mean daily serum TGF-betal concentration beetwen control group and the group with chronic hepatitis type B was shown. Increased expression of mRNA, TGF-betal in bioptate of liver of patients with chronic hepatitis type B in comparison to control group was noted. In "minimal changes" control group presence of significant positive correlation between expression of mRNA TGF-beta1 in liver and concentration of this cytokine in serum was shown, in the group of patients with chronic hepatitis B this connection was not noted.