Improved vessel dilator for percutaneous catheterization

Three commercial vessel dilators and a dilator of an improved design were tested during percutaneous catheterization in 16 mongrel dogs to evaluate arterial damage produced with their use. The results indicate that, although all dilators often produce arterial damage, the improved design produced much less damage. In addition, lesions were less severe overall. The dilator has been safely and successfully used in patients for percutaneous vessel catheterization for the past 30 years at the authors' institution.     

Why HIV Positive Patients on Antiretroviral Treatment and/or Cotrimoxazole Prophylaxis Use Traditional Medicine: Perceptions of Health Workers,Traditional Healers and Patients: A Study in Two Provinces of South Africa

The study explored the perceptions, knowledge and attitudes of patients, health workers and traditional healers about the use of traditional medicine and Anti Retroviral Therapy (ART). The study explored the perceptions, knowledge and attitudes of patients, health workers and traditional healers about the use of traditional medicine and Anti Retroviral Therapy (ART), using an exploratory qualitative design in two provinces of South Africa: an urban township health facility in the Western Cape, and a rural district hospital in KwaZulu-Natal (KZN) with antennal HIV rate of 32% and 28%''respectively. In-depth interviews were conducted with 14 participants: six HIV patients on ART and using Traditional Medicine(TM), two doctors, two nurses and four traditional healers. Two focus group discussions -one at each site - were held with community health workers who work with HIV-positive patients (Western Cape [5] and in KZN [4]). Patient said to have used Traditional Healing Practices (THP) before they were diagnosed with HIV, and some who have been diagnosed with HIV continue using TM in conjunction with ART and/or Cotrimoxazole prophylaxis. Patients preferred not to disclose THP to health professionals because of lack of support and understanding. Patients utilize THP because of family expectations, privacy and confidentiality, especially when they have not disclosed their HIV status. Healthcare professionals had strong negative opinions about THP, especially for HIV-positive patients. Traditional healers supported the patient''s rationale for THP use. This study revealed a need to better understand factors involved in patients'' choosing to use THP concurrently with ART.     

US of the biceps tendon apparatus

High-resolution real-time sonography of the biceps tendon was performed on 80 patients referred for shoulder arthrography. The arthrograms and sonograms were compared at the levels of the biceps tendon groove and distal tendon. Sonography and arthrography were equally successful in facilitating the evaluation of the bony configuration of the biceps tendon groove, but sonography gave a superior image of the biceps tendon within the groove. In 16 patients, biceps tendon sheath effusions or swelling was detected using sonography; 15 of these patients had associated pathologic conditions elsewhere in the joint. Arthrograms did not disclose a biceps tendon or sheath abnormality in any of these patients. We conclude that sonography could be the imaging method of choice in patients with suspected biceps tendon lesions and that the presence of a biceps tendon or sheath abnormality indicates an increased likelihood of abnormalities elsewhere in the joint.     

Effect of natural killer cells on syngeneic bone marrow: in vitro and in vivo studies demonstrating graft failure due to NK cells in an identical twin treated by bone marrow transplantation

Bone marrow transplantation for severe idiopathic aplastic anemia was undertaken in a patient, using his monozygotic twin brother as the donor. In spite of the use of syngeneic bone marrow, failure of engraftment occurred on two occasions. In vitro studies demonstrated that natural killer (NK) cells from the recipient markedly inhibited the growth of donor bone marrow granulocyte progenitor cells. On a third attempt, successful bone marrow engraftment was achieved following high-dose cyclophosphamide, which has previously been shown to be inhibitory to NK cells. We conclude that NK cell activity may play an important role in bone marrow failure as well as being responsible for at least some cases of aplastic anemia.     

In vitro studies of lactoferrin and murine granulopoiesis

Human lactoferrin (LF) has been reported to inhibit in vitro granulopoiesis by means of decreasing colony-stimulating activity production by monocytes. We performed a series of experiments to determine if the reported experimental results could be replicated using highly purified murine LF and murine target cells. Three different types of experiments were performed. (1) Medium was conditioned by lung, femoral shaft, and adherent peritoneal cells in the presence and absence of LF, and the granulopoietic stimulating activity in the conditioned media was assayed by means of a 7-day agar colony assay and a 3-day liquid slide chamber assay, which quantitates 3H-TdR incorporation into DNA. (2) In cultures stimulated by an underlayer of adherent peritoneal cells, marrow cell colony formation in agar was determined after 7 days of culture in the presence or absence of LF. (3) LF was added to 3-day liquid marrow cell cultures that had been stimulated by lung or femoral shaft conditioned media. In all experimental situations, highly purified, iron-saturated LF in concentrations up to 10(-7) M had no effect on in vitro granulopoiesis. These results do not support LF's reputed regulatory role in granulopoiesis.     

Interaction of benzylidene-anabaseine analogues with agonist and allosteric sites on muscle nicotinic acetylcholine receptors

Background and purpose

Benzylidene-anabaseines (BAs) are partial agonists of the α7 nicotinic acetylcholine receptor (nAChR) but their mechanism(s) of action are unknown. Our study explores several possibilities, including direct interactions of BAs with the nAChR channel.

Experimental approach

Functional and radioligand-binding assays were used to examine the interaction of two BA analogues, 3-(2,4-dimethoxybenzylidene)-anabaseine (DMXBA) and its primary metabolite 3-(4-hydroxy-2-methoxybenzylidene)-anabaseine (4OH-DMXBA) with both agonist and non-competitive antagonist (NCA)-binding sites on muscle-type nAChRs.

Key results

Both BAs non-competitively inhibited ACh activation of human fetal muscle nAChRs and sterically inhibited the specific binding of the NCAs [piperidyl-3,4-3H(N)]-(N-(1-(2-thienyl)cyclohexyl)-3,4-piperidine ([³H]TCP) and [³H]dizocilpine to Torpedo nAChRs in the desensitized state. These compounds modulated [³H]tetracaine, [¹⁴C]amobarbital and [³H]TCP binding to resting nAChRs by allosteric mechanisms. Both BAs enhanced [³H]TCP binding when the nAChR was initially in the resting but activatable state, suggesting that both compounds desensitized the Torpedo nAChR. Although DMXBA failed to activate human fetal muscle nAChRs, 4OH-DMXBA was found to be a partial agonist. [³H]Nicotine competition-binding experiments confirmed that 4OH-DMXBA has higher affinity than DMXBA for the agonist sites, and that DMXBA is also a competitive antagonist.

Conclusions and implications

3-(4-hydroxy-2-methoxybenzylidene)-anabaseine is a partial agonist for human fetal muscle nAChRs, whereas DMXBA only has competitive and NCA activities. The NCA-binding site for BAs overlaps both the phencyclidine-and dizocilpine-binding sites in the desensitized Torpedo nAChR ion channel. The desensitizing property of BAs suggests another possible mode of non-competitive inhibition in addition to direct channel-blocking mechanisms.     

Neuroprotection by donepezil against glutamate excitotoxicity involves stimulation of ��7 nicotinic receptors and internalization of NMDA receptors

BACKGROUND AND PURPOSE

Glutamate excitotoxicity may be involved in ischaemic injury to the CNS and some neurodegenerative diseases, such as Alzheimer''s disease. Donepezil, an acetylcholinesterase (AChE) inhibitor, exerts neuroprotective effects. Here we demonstrated a novel mechanism underlying the neuroprotection induced by donepezil.

EXPERIMENTAL APPROACH

Cell damage in primary rat neuron cultures was quantified by lactate dehydrogenase release. Morphological changes associated with neuroprotective effects of nicotine and AChE inhibitors were assessed by immunostaining. Cell surface levels of the glutamate receptor sub-units, NR1 and NR2A, were analyzed using biotinylation. Immunoblot was used to measure protein levels of cleaved caspase-3, total NR1, total NR2A and phosphorylated NR1. Immunoprecipitation was used to measure association of NR1 with the post-synaptic protein, PSD-95. Intracellular Ca²⁺ concentrations were measured with fura 2-acetoxymethylester. Caspase 3-like activity was measured using enzyme substrate, 7-amino-4-methylcoumarin (AMC)-DEVD.

KEY RESULTS

Levels of NR1, a core subunit of the NMDA receptor, on the cell surface were significantly reduced by donepexzil. In addition, glutamate-mediated Ca²⁺ entry was significantly attenuated by donepezil. Methyllycaconitine, an inhibitor of α7 nicotinic acetylcholine receptors (nAChR), inhibited the donepezil-induced attenuation of glutamate-mediated Ca²⁺ entry. {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002, a phosphatidyl inositol 3-kinase (PI3K) inhibitor, had no effect on attenuation of glutamate-mediated Ca²⁺ entry induced by donepezil.

CONCLUSIONS AND IMPLICATIONS

Decreased glutamate toxicity through down-regulation of NMDA receptors, following stimulation of α7 nAChRs, could be another mechanism underlying neuroprotection by donepezil, in addition to up-regulating the PI3K-Akt cascade or defensive system.