Computer-assisted three-dimensional reconstruction of the hippocampal region based on serial sections

A large series of rabbit hippocampal Neo-Timm stained sections were manually aligned, digitized, and by a modified median filtration noise reduced and reconstructed into a three-dimensional object. From the presented simulated grey tone cuts of this object, the reader may assemble a rabbit hippocampal model, that spatially illustrates its anatomy.     

Pinacidil uptake and effects in the isolated rabbit heart

The myocardial accumulation of pinacidil showed one-compartment characteristics with a half-time of 1.11 min., whereas the disposition followed three-compartment kinetics with half-times for the relevant two redistributory and the terminal phases of 0.39, 1.51 and 5.44 min., respectively. At a steady-state drug concentration in the perfusate of 6.12 nmol ml-1, the average concentration of pinacidil in the myocardium was 20.6 nmol g-1. The accumulated amount could predictically be referred with 57% to a central and 31 and 12% to two peripheral (deeper) drug pools. The pharmacodynamic effects of pinacidil in the isolated perfused rabbit heart were studied at stepwise increasing concentrations from 0.15 to 100 microM. Coronary flowrate increased initially up to 24.5% at 1.5 microM pinacidil and then gradually decreased. Amplitude and velocity of contraction were both inhibited in a biphasic way up to 92.7 and 94.1%, respectively. Apparent dynamic steady states developed within 13-15 min. The computer-derived inhibitory Em-values related to the first phase were 49.2 and 52.4% and those related to the second phase were 111.7 and 108.3%, respectively. Heart frequency decreased monophasically and exhibited an inhibitory Em-value of 19.6%. Oxygen consumption decreased at pinacidil concentrations higher than 15 microM and the Em-value was 69.7%. The frequency-corrected QT-interval decreased biphasically and the related inhibitory Em-values were 8.6 and 58.7%. The QRS-interval did not change and the PQ-interval only showed a minor increase at the highest pinacidil concentration. Our findings are compatible with the concept of pinacidil being a potassium channel opener.     

Transplantation of central nervous tissue

Studies of post-lesional reorganization of central nervous connections have shown that central nerve fibers respond to nearby denervation by sprouting and formation of new terminals. The connections in the central nervous system (CNS) are accordingly much more plastic than was thought for a long time. This has revived the interest in transplantation of central nervous tissue. In this study we present some historical data on CNS transplantation supplemented by recent results obtained in our laboratory. Pieces of hippocampal tissue from embryonic or early postnatal rats were transplanted to different parts of the brain of littermates or adult rats. About two-thirds of the transplants were recovered after survival times ranging from 4 d to 2 years, and their cytological organization and intrinsic connections were monitored by cell and fiber stains and histochemical methods (AChE staining and Timm sulphide silver method). Comparison with both a normal and a lesioned control material revealed that in most transplants the tissue had developed as it does when left in situ in the donor brain, but deprived of its major afferent connections. In several instances we found evidence of a major exchange of connections between the transplants and host brains. The conditions needed for this to occur appeared to involve growth stimulation of host brain fibers by transection (host to transplant) and denervation of host neuropil (transplant to host). In cases where these conditions are met, the use of transplants may have future implications in attempts to repair lesions in the central nervous systems.     

Sensory neuropeptides contribute to oedema formation in experimental burns

The role of primary sensory neuropeptides in experimental burns was investigated. It was shown that after scalding, substance P-like immunoreactivity is released into the lymphatic fluid of dogs. Substance P, injected intravenously, was shown to cause dose-dependent oedema formation in rat skin, as measured with the Evans blue-technique. Furthermore, capsaicin pretreatment, which depletes the neuropeptide content of primary sensory neurons, was shown to inhibit late oedema formation in rats.     

Tropical pyomyositis in a temperate climate in an immunocompetent adult.

Tropical pyomyositis, though common in Africa, South America, and the South Pacific, is relatively rare in North America. Reported is the case of a patient who developed chest wall muscle abscesses after sustaining minor chest wall muscle trauma and presented to the emergency department appearing acutely ill. He was treated surgically with irrigation and debridement of the abscesses as well as with antibiotics and recovered fully over a seven-month course. This case illustrates important aspects of tropical pyomyositis with a discussion of the natural history of this disease as well as diagnostic modalities and treatment options for this virulent infectious process that is usually caused by penicillin-resistant Staphylococcus aureus.     

Dose-dependent headache response and dilatation of limb and extracranial arteries after three doses of 5-isosorbide-mononitrate

Summary The aim of the present study was to compare the ability of different doses of isosorbide-5-mononitrate (5-ISMN) to cause dilatation of medium sized and small arteries, and to examine the intensity and duration of any headache produced. Ten healthy volunteers each received 3 doses of 5-ISMN and placebo on separate days. The diameters of the radial and superficial temporal arteries were repeatedly measured with high frequency ultrasound and pain was scored using a 10 point verbal scale.A clear dose-relationship was found for plasma concentrations and headache, and for changes in the diameter of the temporal artery, but not for the radial artery.It is concluded that headache after 5-ISMN is caused by arterial dilatation or by mechanisms responsible for the arterial dilatation. Ultrasound monitoring of arterial diameters is an important and sensitive tool in the evaluation of nitrates and other vasodilators.     

Synthesis of 3'-alkylthio-2',3'-dideoxy nucleosides with potential anti-HIV activity from 2-deoxy-D-ribose, using a phosphorus pentoxide reagent.

Direct condensation of 2-deoxy-D-ribose (1) with mercaptans using the P4O10/H2O/Bu3N reagent in chloroform resulted in coupling at C-3 to give the anomeric mixtures of the corresponding pentopyranoses 2 and pentofuranoses 3. After acetylation with acetic anhydride in dry pyridine of these 3-alkylthio pentofuranoses, coupling with the nucleobases uracil, thymine, and cytosine in accordance with the Friedel-Crafts catalyzed silyl Hilbert-Johnson method yielded the acetylated D-erythro nucleosides 7 as anomeric mixtures, separable only by means of chromatography either before or after deprotection with ammonia. The nucleosides 8a-e were devoid of any activity against HSV-1 and HIV-1.