Expression of metabotropic glutamate receptor 8 in autonomic cell groups of the medulla oblongata of the rat

Metabotropic glutamate receptors (mGluRs) in the medulla oblongata have been suggested to have a functional role in the regulation of cardiovascular baroreflexes. The present study examines the localization of mGluR8 autonomic nuclei of the medulla of the rat. mGluR8 immunoreactivity was observed in the cell bodies and/or processes of the dorsolateral, interstitial, medial, intermediate, ventral, ventrolateral, subpostremal, commissural, parvicellular and gelatinosus subnuclei of the nucleus tractus solitarius (NTS). The intensity of mGluR8 staining was highest in the commissural and interstitial subnuclei at the level of the area postrema. Commissural NTS is involved in regulation of baro-, and chemo-reflexes whereas the interstitial nucleus mediates respiratory reflexes. In the area postrema, diffuse staining was observed in the cell bodies, dendrites and fibers of the dorsal and central regions. In vagal outflow nuclei, mGluR8 immunoreactivity was observed in: (1) the cell bodies and processes of the dorsal motor nucleus of the vagus (DMN) throughout the rostro-caudal extent; and (2) the cell bodies and fibers throughout the rostro-caudal extent of the dorsal and ventral division the nucleus ambiguus (NA). Staining in the ventrolateral medulla was restricted to regions ventral to the nucleus ambiguus and dorsal to the lateral reticulate nucleus. The present study is the first to provide a detailed mapping of mGluR8 within the autonomic nucleii of the medulla and suggests that this subtype may be involved in shaping synaptic transmission in these central nuclei.     

Trypanothione synthetase locus in Trypanosoma cruzi CL Brener strain shows an extensive allelic divergence

The protozoan parasite Trypanosoma cruzi, agent of Chagas' disease, displays an extensive genetic heterogeneity among strains and isolates. It is, therefore, important to determine the degree of polymorphism in potential candidates for drug design. Our studies on the organisation of the locus containing the gene encoding trypanothione synthetase (TcTRS) (an enzyme involved in the unique trypanothione pathway and hence a promising drug target) revealed a high degree of sequence polymorphism between the two alleles in the T. cruzi CL Brener strain, the reference clone for the genome project. The genes linked to the synthetase appeared to be involved in diverse cell-functions, not part of the trypanothione metabolism. The gene synteny was conserved at both allelic loci that were found to reside on a pair of homologous chromosomes with a size difference of about 2 Mb. The allelic polymorphism of TcTRS resulted in a protein sequence divergence of 4%, ten-times higher than in trypanothione reductase (TR), another key enzyme in the same pathway. Such allelic divergence observed in T. cruzi genes might have implications for drug design against Chagas' disease and the evolutional impact of the CL Brener strain.     

Pathophysiology and prognosis in vietnamese adults with tuberculous meningitis

The pathogenesis of tuberculous meningitis remains unclear, and there are few data describing the kinetics of the immune response during the course of its treatment. We measured concentrations of pro- and anti-inflammatory cytokines in serial blood and cerebrospinal fluid (CSF) samples from 21 adults who were being treated for tuberculous meningitis. CSF concentrations of soluble tumor necrosis factor-alpha receptors and of matrix metalloprotein-9 and its tissue inhibitor were also measured, and blood-brain barrier permeability was assessed by the albumin and IgG partition indices. CSF concentrations of lactate, interleukin-8, and interferon-gamma were high before treatment and then decreased rapidly with antituberculosis chemotherapy. However, significant immune activation and blood-brain barrier dysfunction were still apparent after 60 days of treatment. Death was associated with high initial CSF concentrations of lactate, low numbers of white blood cells, in particular neutrophils, and low CSF glucose levels.     

Prostanoid-induced modulation of neuropeptide Y and noradrenaline release from the rat mesenteric bed

1. A variety of prostanoids were examined for their ability to alter the periarterial nerve stimulation-induced release of noradrenaline (NA) and neuropeptide Y immunoreactive compounds (NPY-ir) from the perfused mesenteric arterial bed of the rat. 2. Periarterial nerve stimulation (16 Hz) increased the overflow of NA, NPY-ir and perfusion pressure. 3. The prostacyclin (PGI2) analogues, carbaPGI2 and cicaprost both produced a concentration-dependent attenuation of the nerve stimulation-induced increase in NA, NPY-ir overflow and perfusion pressure. 4. The prostaglandin (PG) analogue PGE2 attenuated the evoked increase in NPY-ir overflow as well as a modest decrease in NA. 5. PGE1, sulprostone and iloprost attenuated the nerve stimulation-induced increase in NA overflow but not NPY-ir. 6. Neither PGF2alpha nor the thromboxane A2 analogue U46619 altered the evoked increase in NA or NPY-ir overflow. 7. The results support the view that sympathetic co-transmitter release can be differentially modulated by paracrine/autocrine mediators at sympathetic neuroeffector junctions.     

Natural anti-HIV agents. Part IV. Anti-HIV constituents from Vatica cinerea

In a continuing search for anti-HIV compounds from plants of Vietnam, 19 compounds, including a new triterpene, were isolated from an extract of the leaves and stem of Vatica cinerea. The new triterpene was determined to be a cycloartane triterpenoid with 29 skeletal carbons and was assigned the name vaticinone (1). The known triterpenes included three cycloartanes, a lanostane, two dammaranes, three lupanes, an ursane, and an oleanane. A chlorophyll isolate was identified as pheophorbide a (13). The majority of the triterpenes, the sesquiterpene, 1-hydroxycyclocolorenone, and pheophorbide a showed anti-HIV activity, with the chlorophyll being the most active, demonstrating an IC(50) value of 1.5 microgram/mL (2.5 microM), while being completely devoid of toxicity up to a concentration of 20 microgram/mL (33.8 microM). Vaticinone (1) was found to inhibit the replication of HIV-1, with an IC(50) value of 6.5 microgram/mL (15.3 microM; selective index = 1.4). The structures of these isolates were determined by spectral data including 1D and 2D NMR spectra.     

Skin-sparing mastectomy and immediate breast reconstruction: a prospective cohort study for the treatment of advanced stages of breast carcinoma

Background Recent published series demonstrate the safety and effectiveness of skin-sparing mastectomy (SSM) with immediate reconstruction for the treatment of early-stage breast carcinoma. Although several reports have retrospectively evaluated outcomes after breast reconstruction for locally advanced disease (stages IIB and III), no study has specifically considered immediate breast reconstruction after SSM for locally advanced disease. Methods From 1996 to 1998, 67 consecutive patients with breast carcinoma underwent SSM with immediate reconstruction and were prospectively observed. From this group of patients, those with locally advanced disease (stage IIB, n=12; stage III, n=13) were analyzed separately. Tumor characteristics, adjuvant therapy, type of reconstruction, operative time, complications, hospital stay, and incidence of local recurrence and distant metastasis were noted. Results Breast reconstruction consisted of a transverse rectus abdominis myocutaneous flap (n=22) or a latissimus flap plus an implant (n=4). The median operative time was 5.5 hours; the average hospital stay was 5.2 days. Complications required reoperation in three patients (12%): partial skin flap necrosis in two and partial abdominal skin necrosis in one. Surgery on the opposite breast for symmetry was required in one patient (4%). Postoperative adjuvant therapy was not significantly delayed (median interval, 32 days). With a median length of follow-up of 49.2 months (range, 33–64 months), local recurrence was present in only one patient (4%), with successful local salvage treatment, and distant metastasis was present in four patients (16%). Conclusions SSM with immediate reconstruction seems safe and effective and has a low morbidity for patients with advanced stages of breast carcinoma. Local recurrence rates and the incidence of distant metastasis are not increased compared with those of patients who have had modified radical mastectomies without reconstruction.