New approach in the treatment of refractory vitiligo: CO2 laser combined with betamethasone and salicylic acid solution

The aim of this study is to evaluate the use of fractional carbon dioxide laser (CO₂) with betamethasone and salicylic acid solution in the treatment of patients with refractory vitiligo in hands. Each hand of the patient was randomly assigned to one of two groups: lesion treated with fractional carbon dioxide laser associated with betamethasone and salicylic acid solution administration or lesion treated only with betamethasone and salicylic acid solution. We conclude that combined treatment with fractional carbon dioxide laser and betamethasone associated with salicylic acid solution could effectively and safely be used in the treatment of refractory vitiligo.     

Primary Somatosensory Cortex Function in Complex Regional Pain Syndrome: A Systematic Review and Meta-Analysis

That complex regional pain syndrome (CRPS) is associated with functional reorganization in the primary somatosensory cortex (S1) is widely accepted and seldom questioned. Despite more than a decade of research, there has been no systematic review of the CRPS literature concerning the changes in S1 function, and therefore the extent of these changes is unclear. Here we conduct a systematic review and meta-analysis to quantify the spatial and temporal aspects of S1 function in CRPS. A comprehensive search strategy identified functional neuroimaging studies of S1 in CRPS. We adhered to a rigorous systematic review protocol when extracting data and appraising risk of bias. Outcomes were grouped into spatial representation; activation levels, including disinhibition; peak latency of activation; and glucose metabolism. Meta-analysis was conducted where possible. Fifteen studies were included, all investigating upper-extremity CRPS. In patients with CRPS, the S1 spatial representation of the affected hand is smaller than that of the unaffected hand and that of non-CRPS controls; however, this evidence comes from only a few studies. There is no difference in activation, disinhibition, or latency of peripherally evoked S1 responses in CRPS. The risk of bias was high across studies, mainly from unclear sampling methods and unblinded analysis of outcomes.     

Oxidative dehalogenation of trichlorophenol catalyzed by a promiscuous artificial heme-enzyme

The miniaturized metalloenzyme Fe(iii)-mimochrome VI*a (Fe(iii)-MC6*a) acts as an excellent biocatalyst in the H₂O₂-mediated oxidative dehalogenation of the well-known pesticide and biocide 2,4,6-trichlorophenol (TCP). The artificial enzyme can oxidize TCP with a catalytic efficiency (k_cat/K^TCP_m = 150 000 mM⁻¹ s⁻¹) up to 1500-fold higher than the most active natural metalloenzyme horseradish peroxidase (HRP). UV-visible and EPR spectroscopies were used to provide indications of the catalytic mechanism. One equivalent of H₂O₂ fully converts Fe(iii)-MC6*a into the oxoferryl-porphyrin radical cation intermediate [(Fe(iv) O)por˙⁺], similarly to peroxidase compound I (Cpd I). Addition of TCP to Cpd I rapidly leads to the formation of the corresponding quinone, while Cpd I decays back to the ferric resting state in the absence of substrate. EPR data suggest a catalytic mechanism involving two consecutive one-electron reactions. All results highlight the value of the miniaturization strategy for the development of chemically stable, highly efficient artificial metalloenzymes as powerful catalysts for the oxidative degradation of toxic pollutants.

The artificial metalloenzyme FeMC6*a is able to perform the H₂O₂-mediated dechlorination of 2,4,6-trichlorophenol with unrivalled catalytic efficiency, highlighting its potential application for the removal of toxic pollutants.     

Phenotype markers and function of neutrophils in children with hemolytic uremic syndrome

The hemolytic uremic syndrome (HUS) is the most-common cause of acute renal failure in children. Several researchers have reported the presence of neutrophil (PMN) activating cytokines, such as interleukin-8 and tumor necrosis factor-α, in the sera of HUS patients. Moreover, PMN-derived products, such as elastase, were increased. These observations have lead to the hypothesis that activated PMN could act as mediators of endothelial damage. The objective of this investigation was to directly evaluate the activation status of peripheral PMN from children with HUS. For this purpose, 12 children with typical HUS were bled during the acute period, before dialysis and/or transfusion, and 8 of them were also bled after 1 month follow-up. Additionally, blood samples from healthy control children admitted for routine surgical procedures, chronic uremic children, and neutrophilic children with acute infections not related to HUS were collected and processed in an identical manner. The function and membrane activation markers of PMN from these groups were evaluated.We found that during the acute period of HUS, PMN had reduced expression of FcγRIII (CD16) and CD11b, were degranulated, and exhibited an impaired antibody-dependent cellular cytotoxicity. These parameters returned to normal after clinical recuperation. We conclude that PMN activation in HUS patients is a very early and transient event, and upon hospitalization before dialysis PMN show a phenotype and functional pattern of partial deactivation. Received: 25 June 2001 / Revised: 16 November 2001 / Accepted: 20 November 2001     

Effects of acute hexarelin administration on cardiac performance in patients with coronary artery disease during by-pass surgery

Growth hormone (GH) secretagogues are synthetic molecules with neuroendocrine but also cardiovascular activities mediated by specific GH secretagogue-receptors. The acute administration of hexarelin, a peptidyl GH secretagogue, increases left ventricular ejection fraction in normal subjects and even in patients with severe GH deficiency. We evaluated cardiac performances in patients with coronary artery disease after acute administration of hexarelin (2.0 microg/kg, i.v.) compared to that in patients given with GH-releasing hormone (GHRH; 2.0 microg/kg, i.v.), recombinant human (rh)-GH (10.0 microg/kg, i.v.) or placebo. Cardiac performance was studied in 24 male patients (age [mean +/- S.E.M.]: 59.5 +/- 1.1 years; body mass index: 24.6 +/- 0.9 kg/m(2); left ventricular ejection fraction: 57.2 +/- 1.4%) with coronary artery disease undergoing by-pass surgery during general anesthesia. Left ventricular ejection fraction, left ventricular end diastolic volume, cardiac index and cardiac output were evaluated by intraoperative omniplane transoesophageal echocardiography while wedge pressure, central venous pressure, mean arterial pressure and systemic vascular resistance index were evaluated by systemic and pulmonary arterial catheterization. RhGH, GHRH and placebo did not exert any hemodynamic effect while hexarelin induced a prompt (after +10 min) increase in left ventricular ejection fraction (P < 0.001), cardiac index (P < 0.001) and cardiac output (P < 0.001) lasting up to +90 min without any variation in left ventricular end diastolic volume. Accordingly, hexarelin induced a reduction of wedge pressure (P < 0.01). These changes occurred in the presence of increased mean arterial pressure (P < 0.05) and transient decrease of central venous pressure (P < 0.05 at +30 min only) but no change in systemic vascular resistance index. Heart rate after hexarelin was similar to that after placebo. Hexarelin induced a slight increase in GH levels which was similar to that after GHRH but far lower (P < 0.01) than that after rhGH. Thus, in patients with coronary artery disease undergoing by-pass surgery, the acute administration of hexarelin clearly improves cardiac performance without any relevant variation in systemic vascular resistance. The cardiotropic effect of hexarelin is not shared by GHRH or by rhGH, indicating that it is not mediated by the increase in circulating GH levels but more likely reflects activation of specific cardiovascular GH secretagogue receptors.     

Dual effect mediated by protease-activated receptors on the mechanical activity of rat colon

1. The present study examined the mechanical effects of agonist enzymes and receptor-activating peptides for protease-activated receptor (PAR)-1 and PAR-2 on longitudinal and circular muscle of rat isolated colonic segments in the attempt to clarify the PAR functional role in intestinal motility. 2. The responses to PAR-1 and PAR-2 activation were examined in vitro by recording simultaneously the changes of endoluminal pressure (index of circular muscle activity) and of isometric tension (index of longitudinal muscle activity). 3. Both PAR-1 agonists, thrombin (0.1 nM - 3 microM) and SFLLRN-NH2 (1 nM - 3 microM), and PAR-2 agonists, trypsin (0.1 nM - 10 microM) and SLIGRL-NH2 (1 nM - 10 microM), induced different effects in the two muscular layers: a reduction of the spontaneous contractions in the circular muscle and a contractile effect or biphasic, relaxation followed by contraction, depending on the concentration, in the longitudinal muscle. 4. The inhibitory effects were greatly reduced or abolished by apamin (0.1 microM) indicating that they mainly occur via activation of Ca2+-dependent small conductance, K+-channels. 5. The responses to PAR-1 and PAR-2 were unaffected by tetrodotoxin (1 microM) or indomethacin (1 microM) suggesting that are independent by products of cyclooxygenase or by neural action potentials. 6. These findings indicate that both PAR-1 and PAR-2 are functionally expressed in rat colon. PARs mediate changes of the mechanical activity of longitudinal and circular muscle which might explain the alterations of colonic motility observed during inflammatory conditions.     

Effects of S 21403 on hormone secretion from isolated rat pancreas at different glucose concentrations

The plasma cholesterol-lowering effect and mechanism thereof of a choleretic phloracetophenone or 2,4,6-trihydroxyacetophenone (THA) were investigated in hypercholesterolemic male hamsters. Intragastric administration of THA (300-600 micromol/kg) twice a day for 7 days to these animals caused a dose- and time-dependent decrease in both plasma cholesterol and triglyceride levels. THA at a dose of 400 micromol/kg reduced the cholesterol and triglyceride levels in plasma to 52% and 25% of the level in corresponding cholesterol-fed controls, respectively, with decreases in both plasma very low density lipoprotein and low density lipoprotein cholesterol but not in high density lipoprotein cholesterol. THA did not significantly alter total hepatic cholesterol content but significantly increased the excretion of both bile acids and cholesterol into the intestinal lumen for elimination. Corresponding to the increase in bile acid excretion, THA caused a seven-fold increase in hepatic cholesterol 7alpha-hydroxylase activity. These results suggest that THA exerts its cholesterol lowering effect by increasing hepatic cholesterol 7alpha-hydroxylase activity which increases hepatic conversion of cholesterol to bile acid for disposal via biliary secretion. This compound may have a potential for future development as a therapeutic agent for lowering lipids in hypercholesterolemic patients.