Reduction In Edema Volume Research Articles

PACS-Integrated Tools for Peritumoral Edema Volumetrics Provide Additional Information to RANO-BM-Based Assessment of Lung Cancer Brain Metastases after Stereotactic Radiotherapy: A Pilot Study.

Stereotactic radiotherapy (SRT) is the standard of care treatment for brain metastases (METS) today. Nevertheless, there is limited understanding of how posttreatment lesional volumetric changes may assist prediction of lesional outcome. This is partly due to the paucity of volumetric segmentation tools. Edema alone can cause significant clinical symptoms and, therefore, needs independent study along with standard measurements of contrast-enhancing tumors. In this study, we aimed to compare volumetric changes of edema to RANO-BM-based measurements of contrast-enhancing lesion size. Patients with NSCLC METS ≥10 mm on post-contrast T1-weighted image and treated with SRT had measurements for up to seven follow-up scans using a PACS-integrated tool segmenting the peritumoral FLAIR hyperintense volume. Two-dimensional contrast-enhancing and volumetric edema changes were compared by creating treatment response curves. Fifty NSCLC METS were included in the study. The initial median peritumoral edema volume post-SRT relative to pre-SRT baseline was 37% (IQR 8-114%). Most of the lesions with edema volume reduction post-SRT experienced no increase in edema during the study. In over 50% of METS, the pattern of edema volume change was different than the pattern of contrast-enhancing lesion change at different timepoints, which was defined as incongruent. Lesions demonstrating incongruence at the first follow-up were more likely to progress subsequently. Therefore, edema assessment of METS post-SRT provides critical additional information to RANO-BM.

Synthesis, Computational Studies, Antioxidant and Anti-Inflammatory Bio-Evaluation of 2,5-Disubstituted-1,3,4-Oxadiazole Derivatives.

The 1,3,4-oxadiazole derivatives Ox-6a-f have been synthesized by incorporating flurbiprofen moiety with the aim to explore the potential of target molecules to decrease the oxidative stress. The title compounds Ox-6a-f were prepared by simple reactions in which a flurbiprofen -COOH group was esterified with methanol in an acid-catalyzed medium, which was then reacted with hydrazine to afford the corresponding hydrazide. The acid hydrazide was then cyclized into 1,3,4-oxadiazole-2-thiol by reacting with CS2 in the presence of KOH. The title compounds Ox-6a-f were synthesized by the reaction of an -SH group with various alkyl/aryl chlorides, which involves an S-alkylation reaction. The structures of the synthesized Ox-6a-f derivatives were ascertained by spectroscopic data. The in silico molecular docking was performed against target proteins cyclooxygenase-2 COX-2 (PDBID 5KIR) and cyclooxygenase-1 COX-1 (PDBID 6Y3C) to determine the binding affinity of the synthesized compounds with these structures. It has been inferred that most of the synthesized compounds bind well with an active binding site of 5KIR compared to 6Y3C, and especially compound Ox-6f showed excellent binding affinity (7.70 kcal/mol) among all synthesized compounds Ox-6a-f. The molecular dynamic (MD) simulation has also been performed to check the stability of docking complexes of ligands with COX-2 by determining their root mean square deviation and root mean square fluctuation. Little fluctuation was observed in case of Ox-6f, which forms the most stable complex with COX-2. The comprehensive antioxidant potential of the synthesized compounds has been evaluated by determining their free radical scavenging activity, including DPPH, OH, nitric oxide (NO), and iron chelation assay. The derivative Ox-6f showed promising results with 80.23% radical scavenging potential at a dose of 100 µg/mL while ascorbic acid exhibited 87.72% inhibition at the same dose. The anti-inflammatory activity of the final products has also been performed, and inflammatory markers were assayed, such as a thiobarbituric acid-reducing substance, nitric oxide, interleukin-6 (IL-6), and COX-2. The derivatives Ox-6d and Ox-6f displayed higher anti-inflammatory activity, exhibiting 70.56% and 74.16% activity, respectively. The results were compared with standard ibuprofen, which showed 84.31% activity at the same dose, 200 µg/mL. The anti-inflammatory potential has been performed by following the carrageen-induced hind paw edema model, and results showed that derivative Ox-6f exhibited 79.83% reduction in edema volume compared to standard ibuprofen, which reduced 84.31% edema volume. As dry lab and wet lab results confirm each other, it has been deduced that derivative Ox-6f may serve as the lead structure to design potent compounds to address oxidative stress.

Anti-Inflammatory Activity of Stem Barks Ethanol Extracts of Asam Kandis On Male White Rats

Inflammation is a complex series of changes in tissue due to tissue injury caused by bacteria, trauma, chemicals, heat, and pain. Gamboge (Garcinia xanthochymus) is a fruit-bearing tree native to Southeast Asia. Plants of the genus garcinia are rich in secondary metabolites such as flavonoids, steroids, and triterpenes which have potential pharmacological activity. This study aimed to determine the anti-inflammatory activity based on the reduction in edema volume of Gamboge (Garcinia xanthochymus) stem bark. The inquiry was experimental. Through maceration, an ethanol extract of the gamboge stem was created. The animals were divided into five groups, each containing five white male rats. The test given was a suspension of gamboge ethanol extract at doses of 200, 400, and 600 mg/kgBW, a negative control of 1% Na CMC suspension, and a positive control of 2.25 mg/kgBW sodium diclofenac. Observations were made for 6 hours, and then data were analyzed using a two-way analysis of variance (ANOVA) test. The results showed that gamboge ethanolic extract was proven to have an anti-inflammatory effect in white male rats induced by carrageenan starting at doses of 200, 400, and 600 mg/kgBW, marked by a significant difference to the negative control (p<0.05). The 600mg/kgBW dose group showed no significantly different results from the positive control group (p>.05). These results concluded that the dose group 600mg/kgBW was the best dose of gamboge stem ethanol extract had an anti-inflammatory activity based on reducing the volume of leg edema of white male rats.
 Keywords: Asam Kandis Stem Bark; Anti-Inflammation; Male White Rats

Oral and Topical Anti-Inflammatory Activity of Jatropha integerrima Leaves Extract in Relation to Its Metabolite Profile.

Jatropha integerrima Jacq., family: Euphorbiaceae, is used in India and subtropical Africa to treat different skin conditions. In this study we evaluated the anti-inflammatory activity of J. integerrima leaves extract (JILE) using rat paw edema model. The extract was administered orally (200 and 400 mg/kg) or applied topically as creams at 2.5, 5, and 10% strength. Four hours post-treatment, maximum reduction of edema volume by 63.09% was observed after oral administration of JILE (400 mg/kg) as compared to indomethacin with 60.43%. The extract anti-inflammatory effect was accompanied by a decrease in NO, prostaglandin PGE2, TNF-α and PKC levels by 19, 29.35, 16.9, and 47.83%, respectively. Additionally, topical applications of JILE showed dose dependent reduction in paw edema and resulted in normalized levels of PGE2, TNF-α, and PKC when used as 10% cream. Signs of inflammations were reduced or absent from paw tissue of animals receiving JILE either orally or topically. Finally, liquid chromatography/mass spectrometry analysis of JILE resulted in the annotation of 133 metabolites including 24 diterpenoids, 19 flavonoids, 10 phenolic acid conjugates, 8 cyclic peptides, 6 phytosterols, 4 sesquiterpenes, and 4 coumarins. Several of the annotated metabolites have known anti-inflammatory activity including vitexin, isovitexin, fraxitin, scopeltin, stigmasterol, and many diterpenoidal derivatives.

Treatment of partial injury of the calcaneus tendon with heterologous fibrin biopolymer and/or photobiomodulation in rats.

The present study aimed to evaluate the new heterologous fibrin biopolymer associated, or not, with photobiomodulation therapy for application in tendon injuries, considered a serious and common orthopedic problem. Thus, 84 Rattus norvegicus had partial transection of the calcaneus tendon (PTCT) and were randomly divided into: control (CG); heterologous fibrin biopolymer (HFB); photobiomodulation (PBM); heterologous fibrin biopolymer + photobiomodulation (HFB + PBM). The animals received HFB immediately after PTCT, while PBM (660nm, 40 mW, 0.23J) started 24h post injury and followed every 24h for 7, 14, and 21days. The results of the edema volume showed that after 24h of PTCT, there was no statistical difference among the groups. After 7, 14, and 21days, it was observed that the treatment groups were effective in reducing edema when compared to the control. The HFB had the highest edema volume reduction after 21days of treatment. The treatment groups did not induce tissue necrosis or infections on the histopathological analysis. Tenocyte proliferation, granulation tissue, and collagen formation were observed in the PTCT area in the HFB and HFB + PBM groups, which culminated a better repair process when compared to the CG in the 3 experimental periods. Interestingly, the PBM group revealed, in histological analysis, major tendon injury after 7days; however, in the periods of 14 and 21days, the PBM had a better repair process compared to the CG. In the quantification of collagen, there was no statistical difference between the groups in the 3 experimental periods. The findings suggest that the HFB and PBM treatments, isolated or associated, were effective in reducing the volume of the edema, stimulating the repair process. However, the use of HFB alone was more effective in promoting the tendon repair process. Thus, the present study consolidates previous studies of tendon repair with this new HFB. Future clinical trials will be needed to validate this proposal.

Three-year follow-up of the compression use in lower limb edema during pregnancy: A case report

Lower limb edema with its accompanying subjective ailments has been increasingly frequent in gravid women and in the postpartum period. The management is essentially non-interventional based on compression therapy (CT) with physical exercise adapted to the severity of venous disease and edema. A case of lower limb edema in a woman in the thirty third week of pregnancy was described. CT including compressive bandaging (CB) by short-stretch bandage and compression garments (CG) with physical activity was applied. Edema volume reduction, changes in consistency from hard to mild in palpation and reduction of accompanying ailments by use of CB after two weeks were observed. Further improvement by use of CG before and after delivery, and 3 years later was confirmed. Compression and physical exercise have a positive impact on edema reduction and leg symptoms intensity during pregnancy and should be recommended.

Effects of dexamethasone in traumatic brain injury patients with pericontusional vasogenic edema: A prospective-observational DTI-MRI study.

Cerebral edema is a frequent and serious complication in traumatic brain injury (TBI) patients. The objective is to study the effect of dexamethasone in patients with brain contusions, and to assess its effect on the vasogenic component of the pericontusional edema.Prospective-observational study to quantify, using magnetic resonance imaging, the volume of the edema before and after 10 days of dexamethasone in patients with brain contusions. Using diffusion tensor imaging, we have examined the effect of dexamethasone on fractional anisotropy (FA) and apparent diffusion coefficient (ADC). To assess changes, the pre- and post-treatment values for each patient were compared using a paired-samples Student t test.We included 30 TBI patients, 15 in each group. The volume of the vasogenic edema in the group of patients treated with dexamethasone decreased from 22 to 19 mL and this decrease was statistically significant (P < .05). Nevertheless, in the non-steroids group the volume of the vasogenic edema increased from 11 to 15 mL. There was a significant decrease in the ADC value (from 1.78–1.59; P < .05); and a significant increase in the FA value (0.09–0.11; P < .05) in the patients treated with dexamethasone.Using diffusion tensor imaging we have shown in a selected group of TBI patients with vasogenic pericontusional edema, a reduction of edema volume, a decrease in the ADC and an increase in the FA after treatment with dexamethasone. However, we have no data if such results are beneficial in terms of improving functional outcome.

Reduction of paw edema and liver oxidative stress in carrageenan-induced acute inflammation by Lobaria pulmonaria and Parmelia caperata, lichen species, in mice.

Paw edema volume reduction is a useful marker in determining the anti-inflammatory effect of drugs and plant extracts in carrageenan-induced acute inflammation. In this study, the anti-inflammatory effect of Lobaria pulmonaria (LP) and Parmelia caperata (PC), two lichen species, was examined in carrageenan-induced mouse paw edema test. Compared to the controls in carrageenan-induced inflammation (n=5/group), our results showed that pretreatment by single oral doses with PC extract (50-500mg/kg) gives better results than LP extract (50-500mg/kg) in terms of anti-edematous activity, as after 4h of carrageenan subplantar injection, paw edema formation was inhibited at 82-99% by PC while at 35-49% by LP. The higher anti-inflammatory effect of PC, at all doses, was also observed on the time-course of carrageenan-induced paw edema, displaying profile closely similar to that obtained with diclofenac (25mg/kg), an anti-inflammatory drug reference (all p<0.001). Both LP and PC, at all doses, significantly ameliorated liver catalase (CAT) activity (all p<0.05). However, superoxide dismutase (SOD) activity, glutathione peroxidase (GPx) activity and glutathione (GSH) levels were found increased in liver of PC- compared to LP-carrageenan-injected mice. Our findings demonstrated on one hand higher preventive effects of PC compared to LP in a mouse carrageenan-induced inflammatory model and suggested, on the other hand, that anti-inflammatory effects elicited by the two lichens were closely associated with the amelioration in the endogenous antioxidant status of liver.

Combination ipilimumab and radiosurgery for brain metastases: tumor, edema, and adverse radiation effects.

OBJECTIVETumor and edema volume changes of brain metastases after stereotactic radiosurgery (SRS) and ipilimumab are not well described, and there is concern regarding the safety of combination treatment. The authors evaluated tumor, edema, and adverse radiation-induced changes after SRS with and without ipilimumab and identified associated risk factors.METHODSThis single-institution retrospective study included 72 patients with melanoma brain metastases treated consecutively with upfront SRS from 2006 to 2015. Concurrent ipilimumab was defined as ipilimumab treatment within 4 weeks of SRS. At baseline and during each follow-up, tumor and edema were measured in 3 orthogonal planes. The (length × width × height/2) formula was used to estimate tumor and edema volumes and was validated in the present study for estimation of edema volume. Tumor and edema volume changes from baseline were compared using the Kruskal-Wallis test. Local failure, lesion hemorrhage, and treatment-related imaging changes (TRICs) were analyzed with the Cox proportional hazards model.RESULTSOf 310 analyzed lesions, 91 were not treated with ipilimumab, 59 were treated with concurrent ipilimumab, and 160 were treated with nonconcurrent ipilimumab. Of 106 randomly selected lesions with measurable peritumoral edema, the mean edema volume by manual contouring was 7.45 cm3 and the mean volume by (length × width × height)/2 formula estimation was 7.79 cm3 with R2 = 0.99 and slope of 1.08 on line of best fit. At 6 months after SRS, the ipilimumab groups had greater tumor (p = 0.001) and edema (p = 0.005) volume reduction than the control group. The concurrent ipilimumab group had the highest rate of lesion response and lowest rate of lesion progression (p = 0.002). Within the concurrent ipilimumab group, SRS dose ≥ 20 Gy was associated with significantly greater median tumor volume reduction at 3 months (p = 0.01) and 6 months (p = 0.02). The concurrent ipilimumab group also had the highest rate of lesion hemorrhage (p = 0.01). Any ipilimumab was associated with higher incidence of symptomatic TRICs (p = 0.005). The overall incidence of pathologically confirmed radiation necrosis (RN) was 2%. In multivariate analysis, tumor and edema response at 3 months were the strongest predictors of local failure (HR 0.131 and HR 0.125) and lesion hemorrhage (HR 0.225 and HR 0.262). Tumor and edema response at 1.5 months were the strongest predictors of TRICs (HR 0.144 and HR 0.297).CONCLUSIONSThe addition of ipilimumab improved tumor and edema volume reduction but was associated with a higher incidence of lesion hemorrhage and symptomatic TRICs. There may be a radiation dose-response relationship between SRS and ipilimumab when administered concurrently. Early tumor and edema response were excellent predictors of subsequent local failure, lesion hemorrhage, and TRICs. The incidence of pathologically proven RN was low, supporting the relative safety of ipilimumab in radiosurgery treatment.

The Effect of Complete Decongestive Therapy on Edema Volume Reduction and Pain in Women With Post Breast Surgery Lymph Edema.

BackgroundUpper extremity lymph edema is the most common side effect of breast cancer treatment that may produce significant physical and psychological morbidity. Pain is the frequent symptom of lymph edema that causes impairment of activities in daily life.ObjectivesThe aim of this study was assessment of the effect of complex decongestive therapy (CDT) on upper extremity lymph edema and pain in women with post breast surgery lymph edema.Patients and MethodsIn this quasi- experimental research with before- after design, 36 women with moderate lymph edema after breast surgery participated in the program. Edema volume was measured by water displacement method; pain values were evaluated by visual analog scale (VAS). Data were recorded before intervention and 2 and 4 weeks after it. CDT included the first phase (intensive phase) and the second phase (maintenance phase). Each phase lasted 2 weeks. After use of Shapiro Wilk test for normality, analysis of variances with GEE and repeated measurements were used to analyze the data.ResultsAfter one month doing CDT program, significant decrease of edema was noticed (P < 0.0001), also pain decreased during 2 and 4 weeks after intervention (P < 0.0001).ConclusionsThis study indicated that CDT program is effective in reducing lymph edema volume and pain in women with moderate post breast surgery lymph edema. It seems that raising patients’ awareness and training healthcare professionals regarding lymph edema preventive strategies have an important role in earlier and better combating this complication.

Complex Decongestive Lymphatic Therapy With or Without Vodder II Manual Lymph Drainage in More Severe Chronic Postmastectomy Upper Limb Lymphedema: A Randomized Noninferiority Prospective Study

ContextComplex decongestive lymphatic therapy (CDT) has been the method of choice in conservative management of lymphedema. Although effective, it is time consuming and manual lymph drainage (MLD) usually requires skilled therapists. ObjectivesThe purpose of this study was to compare the reduction in edema volume in more advanced (≥20% limb volume difference) postmastectomy arm lymphedema achieved by compression bandaging (CB) and physical exercises vs. the same management augmented by an additional 30 minutes of MLD (Vodder II method). MethodsSixty postmastectomy women were randomly assigned to either the CB group or the CDT group. Of those, 51 women (26 within the CB group) completed 26 weeks of therapy (two weeks of the intensive phase and six months of the maintenance phase). ResultsA decrease of limb volume (15.6% in the CB group and 13.8% in the CDT group), edema volume (47.2% and 47.4%, respectively), and limb-related volume change (14.7% and 12.5%) during the intensive phase were observed. This improvement remained constant in both groups after six months of maintenance therapy. The health-related quality of life (measured by the Lymphedema Questionnaire) similarly showed improvement in both groups, with a high level of treatment satisfaction. ConclusionThese results indicate that parallel (immediate and delayed) results may be obtained by CDT without the use of Vodder MLD and CB may be an essential part of lymphedema management.

Antimalarial drug artesunate aff ords protection against carrageenan induced acute infl ammation in rat

Artesunate, an antimalarial drug, has been shown to inhibit the release of inflammatory mediators in various disease conditions. The present study was carried out to evaluate the anti-edematogenic effect of artesunate in the rat paw edema model. Inflammation was induced in the hind paw of rat by sub-plantar injection of 0.1 mL of 0.5% carrageenan and the paw volume was measured up to a fixed mark just before the injection and then after 3 h. The difference in two volumes gave a measure of edema formation. At 3h the level of TNF-α, PGE2 and myeloperoxidase were estimated in the inflamed paw tissue. Treatment of rats with single dose of artesunate at 50 and 150 mg/kg produced a dose-dependent inhibition in paw inflammation where a significant reduction in edema volume and mediator release was observed. Our study shows that by inhibiting the release of inflammatory mediators artesunate affords protection against acute inflammation induced in the rat paw and suggests that it has a potential to be used in the treatment of inflammatory disease conditions.

Effects of manual lymphatic drainage on breast cancer-related lymphedema: a systematic review and meta-analysis of randomized controlled trials

BackgroundLymphedema is a common complication of axillary dissection for breast cancer. We investigated whether manual lymphatic drainage (MLD) could prevent or manage limb edema in women after breast-cancer surgery.MethodsWe performed a systematic review and meta-analysis of published randomized controlled trials (RCTs) to evaluate the effectiveness of MLD in the prevention and treatment of breast-cancer-related lymphedema. The PubMed, EMBASE, CINAHL, Physiotherapy Evidence Database (PEDro), SCOPUS, and Cochrane Central Register of Controlled Trials electronic databases were searched for articles on MLD published before December 2012, with no language restrictions. The primary outcome for prevention was the incidence of postoperative lymphedema. The outcome for management of lymphedema was a reduction in edema volume.ResultsIn total, 10 RCTs with 566 patients were identified. Two studies evaluating the preventive outcome of MLD found no significant difference in the incidence of lymphedema between the MLD and standard treatment groups, with a risk ratio of 0.63 and a 95% confidence interval (CI) of 0.14 to 2.82. Seven studies assessed the reduction in arm volume, and found no significant difference between the MLD and standard treatment groups, with a weighted mean difference of 75.12 (95% CI, −9.34 to 159.58).ConclusionsThe current evidence from RCTs does not support the use of MLD in preventing or treating lymphedema. However, clinical and statistical inconsistencies between the various studies confounded our evaluation of the effect of MLD on breast-cancer-related lymphedema.

Investigation of nano lipid vesicles of methotrexate for anti-rheumatoid activity

BackgroundThe purpose of this study was to formulate and evaluate nano lipid vesicles of methotrexate (MTX) for its anti-rheumatoid activity.MethodsIn this study the principle of both active as well as passive targeting using MTX-loaded stealth liposomes as per the magic gun approach was followed. Stealth liposomes of MTX were prepared by thin-film hydration method using a PEGylated phospholipid-like DSPE-MPEG 2000. Similarly, conventional liposomes were prepared using phospholipids like DPPC and DSPC. Conventional liposomes were coated with a hydrophilic biocompatible polymer like chitosan. They were investigated for their physical properties and in vitro release profile. Further, in vivo screening of the formulations for their anti-rheumatoid efficacy was carried out in rats. Rheumatoid arthritis was induced in male Wistar-Lewis rats using complete Freund’s adjuvant (1 mg/mL Mycobacterium tuberculosis, heat killed in mineral oil).ResultsIt was found that chitosan coating of the conventional liposomes increased the physical stability of the liposomal suspension as well as its entrapment efficiency. The size of the unsonicated lipid vesicles was found to be in the range of 8–10 μm, and the sonicated lipid vesicles in the range of 210–260 nm, with good polydispersity index. Further, chitosan-coated conventional liposomes and the PEGylated liposomes released the drug for a prolonged period of time, compared to the uncoated conventional liposomes. It was found that there was a significant reduction in edema volume in the rat group administered with the test stealth liposomal formulations and chitosan-coated conventional liposomes (PEGylated and chitosan-coated conventional) compared to that of the control and standard (administered with free MTX) group of rats. PEGylated liposomes showed almost equal efficacy as that of the chitosan-coated conventional liposomes.ConclusionLipid nano vesicles of MTX can be administered by intravenous route, whereby the drug selectively reaches the target site with reduced toxicity to other organs.

What Factors Predict the Response of Larger Brain Metastases to Radiosurgery?

Approximately 20 to 40% of patients with systemic malignancies develop brain metastases. To assess the potential role of stereotactic radiosurgery (SRS) for larger metastatic brain tumors, we reviewed our recent experience. Between 2004 and 2008, 70 patients with a metastatic brain tumor larger than 3 cm in maximum diameter underwent Gamma knife SRS. Thirty-three patients had received previous whole brain radiation therapy (WBRT) and 37 received only SRS. The overall median follow-up was 8.1 months. At the first planned imaging follow-up at 2 months, 29 (41%) tumors had >50% volume reduction, 22 (31%) had 10 to 50% volume reduction, and 19 (28%) were stable or larger. We also evaluated brain edema using MRI T2 images. In 11 patients (16%) the peritumoral edema volume was reduced by more than 50%, in 25 (36%) it was reduced by 10 to 50%, in 21 (30%) it was stable, and in 13 (19%) it was increased. Twenty (36%) discontinued corticosteroids by the time of first imaging follow-up. Because of persistent symptoms, 7 patients (10%) required a craniotomy to remove the tumor. Tumor volume reduction (>50%) was associated with a single metastasis (P=.012), no previous WBRT (P=.002), and a tumor volume<16 cm3 (P=.002). The better peritumoral edema volume reduction (>50%) was associated with a single metastasis (P=.024), no previous WBRT (P=.05), and breast cancer histology (P=.044). Surgical resection remains the primary approach for larger brain metastases if feasible. Tumor volume is a better indicator than maximum diameter. Tumor volume and edema responded better in patients who underwent SRS alone.

Characterization of Eltenac and novel COX-2 selective thiopheneacetic acid analogues in vitro and in vivo

We assessed the effect of novel selective thiopheneacetic acids on cyclooxygenase isoenzymes in vitro and in vivo. Thiopheneacetic acid Eltenac and derivatives were investigated in this study. In human whole blood experiments these derivatives were potent inhibitors of COX-2 (IC 50 = 0.02–0.4 μM) with less pronounced effect on COX-1 (IC 50 = 0.15–5.6 μM). With COX-1/COX-2 ratios between 7.5- and 16-fold they are in the range of Celecoxib (13-fold). The parent drug Eltenac demonstrated no selectivity for COX-2. In a rat paw edema model, these compounds showed reduction of edema volume in the range of 36–45% at 10 mg/kg (Eltenac 52%, Diclofenac 51%). However, the compounds were superior to Diclofenac and Eltenac with respect to their ulcerogenic and gastrointestinal properties. Introduction of a nitrate-ester moiety to either Eltenac or a derivative did neither improve selectivity or potency in vitro , nor ulcerogenicity in vivo. Molecular modeling of selective thiopheneacetic acid derivatives to the active site of human COX-2 suggested similar binding properties as Lumiracoxib and Diclofenac. In summary, modification of Eltenac generates moderately selective COX-2 drugs in the range of Celecoxib with respect to potency and selectivity. The drugs showed potent anti-inflammatory properties and significant improvement of animal survival in a sub-chronical experimental set up. Thiopheneacetic derivatives are characterized by low p K a values, short microsomal half-lives and binding mode to COX-2 similar to Diclofenac and Lumiracoxib. These properties may also have an impact on the transient inhibition of COX-2-dependent prostacyclin, thereby being less associated with vascular complications.

Stereotactic Aspiration-Thrombolysis of Intracerebral Hemorrhage and its Impact on Perihematoma Brain Edema

Recent reports suggest that when thrombolytic agents are administered within the clot, lysis rate accelerates at the expense of increased risk of worsening edema. To test this hypothesis, we report on the volumetric analysis of (1) the intraparenchymal hematoma and, (2) perihematomal edema in a cohort of ICH patients treated with intraclot rtPA. A convenience sample of highly selected ICH patients underwent frameless stereotactic aspiration and thrombolysis (FAST) of the clot. Two milligrams of rtPA were administered every 12 h until ICH volume < or =10 cc, or catheter fenestrations were no longer in continuity with the clot. ICH and perihematomal edema volumes were calculated from CT scans. Using random effects linear regression we estimated the rate of hematoma and edema volume resolution as well as their relationship during the first 8 days of lytic therapy. Fifteen patients were treated, mean age: 60.7 years, median time from ictus to FAST: 1 (range 0-3) day. Using a random effects model that considered volume resolution over the first 8 days following lytic therapy we found that the both percentage hematoma and percentage perihematoma edema resolution per day were quadratic with respect to time. Percentage residual hematoma volume on day K = 97.7% - [24.36%*K] + [1.89%*K (2)]; P < 0.001 for both terms. Percentage residual edema on day K = 97.4% - [13.94%*K] + [1.30%*K (2)]; P < 0.001 for K and P = 0.01 for K (2). Examination of each patient's volume data suggests that there exists a strong direct relationship between perihematoma edema volume and same day hematoma volume. In this cohort of ICH patients treated using FAST, volumetric analysis of ICH and perihematomal edema seems to suggest that local use of rtPA does not exacerbate brain edema formation. Furthermore, there seems to be a strong association between reduction in ICH volume and reduction in edema volume, as would be expected following the concept of "hemotoxicity" postulated by some investigators.

Effectiveness of the treatment-phase of two-phase complex decongestive physiotherapy for the treatment of extremity lymphedema

Complex decongestive physiotherapy (CDP) consists of a two-phase treatment program and is the international standard therapy for lymphedema. However, this therapy is not performed at most hospitals in Japan. The subjects of the present study were 82 Japanese women with lymphedema of an extremity (median age, 64 years; range, 40-86 years). The volume of the affected extremity was compared before and after therapy, and the duration of the CDP treatment phase and rate of edema reduction were ascertained. The associations between the effect of CDP and duration of lymphedema, operative procedure, and radiotherapy were also investigated. For patients with upper-extremity lymphedema, the median duration of the CDP treatment phase was 6 treatment days (range, 3-26 days), median reduction of edema volume was 328.7 ml (range, 76.6-1258.0 ml; P = 0.0014), and median rate of edema reduction was 58.9% (range, 42.7%-97.1%). For patients with lower-extremity lymphedema, the median duration of the CDP treatment phase was 10 treatment days (range, 2-35 days), median reduction of edema volume was 1573.7 ml (range, 293.9-3471.1 ml; P < 0.0001), and median rate of edema reduction was 73.4% (range, 29.2%-117.3%). Although no correlation was seen between duration of lymphedema and duration of the CDP treatment phase or rate of edema reduction, the degree of lymph node dissection tended to influence rate of edema reduction in patients with lower-extremity lymphedema. In a study of Japanese women with lymphedema, CDP comprising a two-phase treatment program was clearly effective.

Melatonin reduces cerebral edema formation caused by transient forebrain ischemia in rats

Reduction of cerebral edema, an early symptom of ischemia, is one of the most important remedies for reducing subsequent chronic neural damage in stroke. Melatonin, a metabolite of tryptophan released from the pineal gland, has been found to be effective against neurotoxicity in vitro. The present study was aimed to demonstrate the effectiveness of melatonin in vivo in reducing ischemia-induced edema using magnetic resonance imaging (MRI). Rats were subjected to middle cerebral artery (MCA) occlusion/reperfusion surgery. Melatonin was administered twice (6.0 mg/kg, p.o.): just prior to 1 h MCA occlusion and 1 day after the surgery. T 2-weighted multislice spin-echo images were acquired 1 day after the surgery. Increases in T 2-weighted signals in ischemic sites of the brain were clearly observed after MCA occlusion. The signal increase was found mainly in the striatum and in the cerebral cortex in saline-treated control rats. In the melatonin-treated group, the total volume of cerebral edema was reduced by 45.3% compared to control group ( P < 0.01). The protective effect of melatonin against cerebral edema was more clearly observed in the cerebral cortex (reduced by 56.1%, P < 0.01), while the reduction of edema volume in the striatum was weak (reduced by 23.0%). The present MRI study clearly demonstrated that melatonin is effective in reducing edema formation in ischemic animals in vivo, especially in the cerebral cortex. Melatonin may be highly useful in preventing cortical dysfunctions such as motor, sensory, memory, and psychological impairments.

Frontiers in lymphatic microsurgery.

The Authors report an overview on the modern surgical treatment of peripheral lymphoedema. The aim of lymphatic microsurgical operations is to drain the lymph either toward the venous circulation (lympho-venous shunts) or the lymphatic collectors above the obstacle to the lymph flow, with the interposition of lymphatic or venous grafts (lymphatic-venous-lymphatic plasty). Selection of candidate patients for lymphatic microsurgery is based on an adequate diagnostic investigation, which includes above all lymphoscintigraphy, conventional oil contrast lymphangiography, Doppler venous flowmetry and manometry, and, if necessary (angiodysplasias), an accurate study also of the artery circulation. The clinical outcome of lymphatic microsurgery, assessed by water volumetry and lymphangioscintigraphy, performed at variable distance of time from operations till over 5 years after surgery, shows a significant reduction of edema volume and improvement of lymph flow in all patients and that the more precocious the microsurgical treatment the better the results.