Central nervous system nitric oxide formation in cerebral systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an inflammatory disease in which up to two thirds of the patients present neurological symptoms. The diagnosis of the disease is based on clinical findings and the presence of autoantibodies, and the pathogenesis is unclear. The purpose of this study was to determine if the pathogenesis was partly mediated via nitric oxide (NO) formation. Cerebrospinal fluid (CSF) samples from 15 patients with cerebral SLE were analyzed for the NO metabolites nitrite and nitrate using capillary electrophoresis. The severity of neurological symptoms was scored by dividing the patients into two groups with either mild or moderate/severe CNS involvement. All patients with cerebral SLE showed increased levels of NO metabolites. In CSF, there was a relationship between signs of NO production and clinical results showing that increased levels of nitrite and nitrate were associated with more severe neurological symptoms. These findings may shed new light on the pathogenesis of cerebral SLE, and analysis of nitrate and nitrate may prove to be of value in monitoring the activity of the disease.     

Pre-emptive glycopyrrolate 0.2 mg and bradycardia during gynaecological laparoscopy with mivacurium

In a prospective, randomized, double-blind, placebo-controlled trial, the effect of pre-emptive glycopyrrolate 0.2 mg given intravenously on the incidence of bradycardia in patients undergoing elective gynaecological laparoscopy with mivacurium neuromuscular blockade was investigated. Seven out of 32 (21.6%) control patients developed bradycardia (heart rate < 50 min-1), compared with 3 of 31 (9.6%) patients receiving glycopyrrolate (P = 0.4). Glycopyrrolate 0.2 mg, given immediately before induction in gynaecological laparoscopy with mivacurium, did not significantly reduce the incidence of intraoperative bradycardia.     

Therapy of dislocated calcaneus joint fracture with the AO calcaneus plate

From August 1992 to March 1997, 66 patients with 71 displaced intraarticular calcaneal fractures were prospectively examined after an operative treatment using an extended lateral approach and the ASIF calcaneal plate followed by early functional postoperative treatment (mean follow-up 25 months, retrieval rate 96%). To classify the type of fracture and to verify the results of reduction and of retention CT scans in the coronal and transverse plane were performed pre- and postoperatively and on the day of assessment. The Zwipp Score was used for clinical evaluation. After fractures with 5 to 8 points according to the calcaneal fracture scale, 97% of the patients had an anatomical or near anatomical reduction of the posterior facet and the clinical outcome in 82% of the patients was graded as good or excellent. In 70% of patients with a fracture rated 9 to 10 points a good reduction was demonstrated and clinically there were 67% good or excellent results. But in the fractures with 11 to 12 points, despite 40% good reductions, the clinical outcome was graded as good in 10% of the patients only. However, if the post-operative displacement of the posterior facet was more than 2 mm no patient had a good result independent of the type of fracture. Due to restoration of the geometry of the most comminuted fracture types and the immediate partial weight bearing secondary soft tissue problems could be minimized without any loss of articular reduction. Anatomical reduction and stable internal fixation together with adequate physical therapy are apparently preconditions but not a guarantee for a good clinical result after displaced calcaneal fractures.     

Effects of estrogen on tight junctional resistance in cultured human umbilical vein endothelial cells

OBJECTIVE: To study the effects of estrogen on transendothelial paracellular permeability in women. METHODS: Human umbilical vein endothelial cells (HUVEC) obtained from women were grown on filters. The paracellular permeability characteristics were determined in terms of changes in the permeability to the polar acid pyranine (Ppyr) and as changes in the transendothelial electrical resistance (RTE). Tight junctional resistance characteristics were assayed by lowering luminal NaCl and measuring the dilution potential, and were expressed as the ratio of monoion mobility uCl/uNa (cation selectivity). RESULTS: Low extracellular calcium and hyperosmolarity increased Ppyr and decreased RTE. The former but not the latter condition abolished the endothelium-specific cation selectivity. Treatment with 10 nM of estradiol-17 beta had no effect on RTE, but it increased the cation selectivity. The effect of estradiol required 1-6 hours' incubation with the hormone; it was dose dependent and saturable, with a median effective concentration of estradiol of 1 nM. Diethylstilbestrol, but not estriol, could mimic the effect of estradiol, and the estrogen receptor antagonist ICI-182, 780 blocked it. CONCLUSION: Cultured HUVEC cells form patent tight junctions. Estrogens increase the cation selectivity across HUVEC cultures. The effect of estrogen may be mediated by an estrogen receptor. These effects may be important for vasculoprotection in cases of sudden changes in ions levels across the capillary wall, such as ischemia or reperfusion.     

Population structure and physiological changes within a hot spring microbial mat community following disturbance

The influence of disturbance on a hot spring cyanobacterial mat community was investigated by physically removing the top 3.0 mm, which included the entire cyanobacterial layer. Changes in 16S rRNA-defined populations were monitored by denaturing gradient gel electrophoresis analysis of PCR-amplified 16S rRNA gene segments. Some previously absent cyanobacterial populations colonized the disturbed areas, while some populations which were present before the disturbance remained absent for up to 40 days. Changes in physiological activity were measured by oxygen microelectrode analyses and by 14CO2 incorporation into cyanobacterial molecular components. These investigations indicated substantial differences between the disturbed and undisturbed mats, including an unexplained light-induced oxygen consumption in the freshly exposed mat, increased carbon partitioning by phototrophs into growth-related macromolecules, bimodal vertical photosynthesis profiles, and delayed recovery of respiration relative to photosynthesis.     

Complete clinical remission and subsequent relapse of bronchiectasis-related (AA) amyloid induced nephrotic syndrome

Systemic amyloidosis normally has a dismal prognosis. However, there are several case reports of protracted survival, usually as a response to measures designed to retard the further deposition of amyloid fibrils. In AA amyloid, most commonly associated with inflammatory rheumatological, bowel, and chest diseases, such interventions have had some success, but the dramatic response of complete resolution of nephrotic syndrome as a result of the regular institution of postural chest drainage and antibiotic therapy, in the clinical context of bronchiectasis, has been previously reported only once. In both of our cases, after protracted remission, such therapy was abandoned by the patients, leading both to recurrence of nephrotic syndrome and also eventually to end-stage renal failure requiring dialysis.     

(Pheo)melanin photosensitizes UVA-induced DNA damage in cultured human melanocytes

The question of whether melanins are photoprotecting and/or photosensitizing in human skin cells continues to be debated. To evaluate the role of melanin upon UVA irradiation, DNA single-strand breaks (ssb) were measured in human melanocytes differing only in the amount of pigment produced by culturing at two different concentrations, basic (0.01 mM) or high (0.2 mM), of L-tyrosine, the main precursor of melanin. In parallel, pheo- and total melanin contents of the cells were determined. Identical experiments were performed with two melanocyte cultures derived from a skin type I and a skin type VI individual. For the first time the correlation between UVA-induced genotoxicity and pheo-/total melanin content has been investigated. We observed that cultured in basic medium, the skin type VI melanocytes contained 10 times more total melanin and about seven times more pheomelanin than the skin type I melanocytes. Elevation of tyrosine level in the culture medium resulted in an increase of both pheo- and total melanin levels in both melanocyte cultures; however, the melanin composition of skin type I melanocytes became more pheomelanogenic, whereas that of skin type VI melanocytes remained the same. The skin type VI melanocytes cultured in basic medium demonstrated a very high sensitivity (1.18 ssb per 10(10) Da per kJ per m2) toward UVA that is probably related to their high pheo- and total melanin content. Their UVA sensitivity, however, did not change after increasing their melanin content by culturing at high tyrosine concentration. In contrast, the skin type I melanocytes demonstrated a low sensitivity (0.04 ssb per 10(10) Da per kJ per m2) toward UVA when cultured in basic medium, but increasing their melanin content resulted in a 3-fold increase in their UVA sensitivity (0.13 ssb per 10(10) Da per kJ per m2). These results demonstrate that UVA-irradiated cultured human melanocytes are photosensitized by their own synthesized chromophores, most likely pheomelanin and/or melanin intermediates.