The influence of antiadhesion therapies on leukocyte subset accumulation in central nervous system ischemia in rats

Although treatment with agents that block leukocyte function, including anti-ICAM-1 and doxycycline, reduces experimental central nervous system (CNS) ischemic injury, it is not known how leukocyte subset accumulation is affected by these agents. Using the rat two-vessel occlusion model and immunohistochemistry, we investigated granulocyte (PMN) and monocyte/macrophage (Mφ) accumulation at 1 and 4 d postischemia. A total of 24 animals were randomized to sham surgery, or to ischemia with saline, anti-ICAM-1, or doxycycline treatments. No leukocytes were observed in sham animals. At 24 h postischemia, there was a moderate infiltration of PMN and Mφ in untreated animals that was significantly decreased with either treatment. At 4 d after ischemia no PMN were identified, with extensive Mφ accumulation occurring in untreated animals that was only partially reduced with doxycycline treatment. These results confirm that both anti-ICAM-1 and doxycycline treatments reduce PMN and Mφ infiltration at 24 h. Delayed Mφ accumulation occurs despite treatment, suggesting that some of these cells represent transformed resident microglia.     

Horizontal alveolar distraction: a surgical technique with the transport segment pedicled to the mucoperiosteum.

PURPOSE: The study goal was to describe a surgical technique for performing horizontal alveolar distraction with the aim of increasing the width of alveolar ridges that are too narrow for dental implant placement. MATERIALS AND METHODS: A transport segment is cut from the vestibular side of the ridge, using osteotomes, and maintaining extensive attachment to the mucoperiosteum. The distraction screw is placed through the vestibular mucosa and the transport segment, in vestibular-palatal direction. Distraction is then performed to increase ridge width. RESULTS: We successfully applied this technique in a patient who required 2 dental implants at adjacent sites in the upper jaw but whose alveolar ridge was too narrow for direct implantation. With horizontal distraction, ridge width was successfully increased, allowing placement of the 2 implants (diameter, 3.3 and 4.1 mm). CONCLUSION: This technique shows promise for patients requiring implants in a narrow alveolar ridge. Depending on each patients specific requirements, we suggest that it be taken into account as a possible alternative to existing techniques.     

Nasal administration of osteopontin peptide mimetics confers neuroprotection in stroke.

Osteopontin (OPN), a large secreted glycoprotein with an arginine, glycine, aspartate (RGD) motif, can bind and signal through cellular integrin receptors. We have shown previously that OPN enhances neuronal survival in the setting of ischemia. Here, we sought to increase the neuroprotective potency of OPN and improve the method of delivery with the goal of identifying a treatment for stroke in humans. We show that thrombin cleavage of OPN improves its ability to ligate integrin receptors and its neuroprotective capacity in models of ischemia. Thrombin-cleaved OPN is a twofold more effective neuroprotectant than the untreated molecule. We also tested whether OPN could be administered intranasally and found that it is efficiently targeted to the brain via intranasal delivery. Furthermore, intranasal administration of thrombin-treated OPN confers protection against ischemic brain injury. Osteopontin mimetics based on the peptide sequences located either N or C terminal to the thrombin cleavage site were generated and tested in models of ischemia. Treatment with successively shorter N-terminal peptides and a phosphorylated C-terminal peptide provided significant neuroprotection against ischemic injury. These findings show that OPN mimetics offer promise for development into new drugs for the treatment of stroke.     

Synthesis and activity of a potent N-methyl-D-aspartic acid agonist, trans-1-aminocyclobutane-1,3-dicarboxylic acid, and related phosphonic and carboxylic acids

We report the synthesis of a series of 3-carboxy-, 3-(carboxymethyl)-, 3-(omega-phosphonoalkyl)-1-aminocyclobutane-1-carboxylic acids for evaluation as agonists or antagonists of neurotransmission at excitatory amino acid receptors, particularly N-methyl-D-aspartic acid (NMDA) receptors. The compounds were evaluated as agonists on their ability to depolarize the rat brain cortical wedge preparation or as antagonist of the actions of the selective agonists NMDA, quisqualic acid, and kainic acid. The chain-elongated glutamate derivatives with potential antagonist activity proved to be weak and frequently nonselective antagonists in this assay. The most noteworthy result was that trans isomer 7b was a very potent agonist, approximately 20 times more active than NMDA at NMDA receptors, while the cis isomer was 1/3 as potent as NMDA.     

Metabolic and biochemical abnormalities of articular cartilage induced by implantation of a sterile sheet of polyethylene in the rabbit patellofemoral joint

A polyethylene sheet was implanted in the patellofemoral joint of the right knee of the rabbit and the biochemical and metabolic changes in the articular cartilage from femoral trochleas (in contact with the implant) and femoral condyles (free of direct contact) were compared with those in their sham-operated counterparts 7, 15, and 30 days after joint implantation. The results showed that there was an increase in the water content; the extraction yields of uronic acid--, 35SO4-, and [3H]glycine-containing compounds; and the incorporation of [3H]thymidine, [3H]glycine, and 35SO4. Concomitantly, the contents of uronic acid--, hexosamine-, neutral sugars-, and hydroxyproline-containing substances decreased in the femoral trochlear cartilage and, to a much lesser extent, in the femoral condylar cartilage from implanted joints. The increased capacity of viable chondrocytes to incorporate metabolic radiolabeled precursors into newly synthesized macromolecules may represent a reparative cell response to the tissue injury induced by the implant. This is therefore a useful model for studying the response of chondrocytes to mechanical injury and tissue tolerance to intraarticularly implanted prosthetic materials.     

Structural and biochemical abnormalities of articular cartilage in rheumatoid arthritis

Compared with normal cartilage, the water content, extraction yields, and capacity of 34SO4 incorporation, were found to be increased in articular cartilage from rheumatoid joints, which also synthesizes an increased proportion of low and middle density small size proteoglycans (PGs), enriched in dermatan sulfate. These small [35S]-PGs also possess longer glycosaminoglycan side chains and lack the ability to interact with hyaluronan. An altered pattern of PG synthesis of rheumatoid chondrocytes may contribute to cartilage damage in this condition.     

Prevalence of the palmaris longus through clinical evaluation

Purpose  

Most standard textbooks of hand surgery report on the rate of palmaris longus muscle absence of 15%. The aim of the study was to determine the absence of palmaris longus and to correlate it with age, sex and body side.     

Auswirkungen des K+-Kanalblockers Tedisamil auf H?modynamik, Myokardisch?mie und neurohumorales System bei Patienten mit stabiler Angina pectoris.?Ein Vergleich mit dem β-Blocker Atenolol

Klinische Limitationen bei der Behandlung der stabilen Angina pectoris mittels Betablocker führten zur Entwicklung von alternativen frequenzsenkenden Substanzen wie beispielsweise dem K⁺-Kanalblocker Tedisamil, der neben antiisch?mischen auch antiarrhythmische Eigenschaften aufweist. In der vorliegenden Untersuchung (doppelblinder, randomisierter Gruppenvergleich) wurden die h?modynamischen, antiisch?mischen, metabolischen und neurohumoralen Auswirkungen von 2× 100 mg Tedisamil und 2× 50 mg Atenolol als Monotherapie bei 48 Patienten mit stabiler Angina pectoris über einen Zeitraum von 6 Tagen verglichen. Tedisamil und Atenolol führten zu einer Senkung der Herzfrequenz sowohl in Ruhe (Tag 1: –14 vs –15 min^-1; p > 0,05; Tag 6: –15 vs –22 min^-1; p > 0,05) als auch unter Belastung (Tag 1: –9 vs –18 min^-1; p = 0,001; Tag 6: –12 vs –25 min^-1; p = 0,001) bei gleichzeitiger Erh?hung der Angina-pectoris-Schwelle. Das Herzzeitvolumen wurde unter beiden Substanzen sowohl in Ruhe (Tag 1: –1,01 vs –1,19 l/min; p > 0,05; Tag 6: –0,86 vs –1,01 l/min; p > 0,05) als auch unter Belastung (Tag 1: –0,82 vs –1,28 l/min; p > 0,05); Tag 6: –0,65 vs –2,68 l/min; p = 0,03) gesenkt, wobei das Schlagvolumen unver?ndert blieb. Der rechtsatriale Druck ?nderte sich nur unter Belastung mit einem Abfall unter Tedisamil (–1,7 mm Hg) und einem Anstieg unter Atenolol (+3,7 mm Hg) (p = 0,001). In der Tedisamil-Gruppe fiel der mittlere pulmonalkapill?re Verschlu?druck am 6. Behandlungstag sowohl in Ruhe (–0,5 mm Hg) als auch unter Belastung (–6,9 mm Hg), zeigte jedoch unter Atenolol eine Tendenz zum Anstieg (Ruhe: +1,7 mm Hg; Belastung: +3,7 mm Hg) (p = 0,03). Eine Senkung des arteriellen Druckes zeigte sich nur unter Behandlung mit Atenolol. W?hrend die belastungsinduzierten Noradrenalin-Plasmaspiegel nach Tedisamil-Gabe gesenkt wurden (–93 pg/ml), zeigte sich unter Atenolol eine Erh?hung (+172 pg/ml) (p = 0,001). Nach Tedisamil fand sich eine im Vergleich zu Atenolol signifikante Verl?ngerung des QT_c-Intervalls (+31 vs –8 ms) 8p = 0,002) bei einem Ausgangswert von 0,408 ± 0,018 und unver?nderten PQ- und QRS-Zeiten. In der vorliegenden Studie zeigte Tedisamil günstige h?modynamische, metabolische und neurohumorale Effekte bei Patienten mit stabiler Angina pectoris. Die antiisch?mische Wirkung von Tedisamil, gemessen an der ST-Strecken-Senkung und der Angina-pectoris-Schwelle, ist mit der von Atenolol vergleichbar.