Expression patterns of PD-L1 and other immune checkpoint molecules in gastric cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 49-49
Author(s):  
Kenichi Nakamura ◽  
Keiichi Hatakeyama ◽  
Tetsuro Toriumi ◽  
Yusuke Koseki ◽  
Yuhei Waki ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Combination Therapy ◽  
Immune Checkpoint ◽  
Expression Patterns ◽  
Immune Checkpoint Molecules ◽  
New Strategy ◽  
Group A ◽  
Tcga Dataset ◽  
Group B

49 Background: Immune checkpoint inhibitors (ICPIs) have provided clinical benefit for various malignancies. A new attempt was recently made to combine PD-1/PD-L1 inhibitors and other ICPIs. In order to establish a new strategy for ICPI combination therapy, we must first understand the expression patterns of PD-L1 and other ICP molecules. To identify possible candidate agents for application in combination therapy with PD-1/PD-L1, we analyzed the expression patterns of ICP molecules in gastric cancer. Methods: Tumor samples were obtained from 278 patients who underwent gastrectomy for gastric cancer from 2014 to 2016, and a comprehensive gene expression analysis using a DNA microarray. We analyzed the TCGA dataset to identify the candidate ICP molecules in relation to PD-L1. The immune landscape was evaluated according to the expression patterns of known immune cell markers reported by Bindea et al. Results: Seven ICP molecules ( PD-L2, IDO1, CD80, ICOS, CTLA4, LAG3 and TIM3) were coexpressed with PD-L1 in the TCGA dataset. In our cohort, all of these molecules were also coexpressed (R > 0.5, P < 0.0001). Using a cluster analysis based on these gene expression profiles, patients were divided into Group A, characterized by the co-overexpression of PD-L1 and other ICP molecules, and Group B, characterized by the underexpression of PD-L1. In Group A, PD-L2 (R = 0.67) and IDO1 (R = 0.61) were particularly strongly associated with the PD-L1 expression. In Group B, elevated expressions of CTLA4 and ICOS were predominantly observed, and these expressions were strongly correlated with each other (R = 0.90). The tumor stage was significantly more advanced in Group B than in Group A (P = 0.02). Accordingly, Group A exhibited a better survival outcome than Group B. The immune landscape of Group A was particularly enriched for Th1, NK CD56dim and activated dendritic cells. Conclusions: PD-L1 and several immune checkpoint molecules tend to be coexpressed in gastric cancer. The combination of PD-L1/-L2 and IDO1 target agents may be a new strategy for treating gastric cancer with PD-L1 overexpression. In contrast, the underexpression of PD-L1 might be an indication for the use of CTLA4- and/or ICOS-directed therapies.

scholarly journals comparison of Efficacy of Topical Ciprofloxacin Ear drops (0.6%) Versus a Combination of Systemic with Topical Ciprofloxacin in Treating Chronically Discharging Ears

Esculapio ◽  
2020 ◽  
Vol 16 (03, july 2020-Septmber 2020) ◽  
Author(s):  
Sarwat Hassan Syed ◽  
Damish Arsalan ◽  
Ghulam Murtaza ◽  
Mohammad Qamar Nasir ◽  
Muhammad Awais Amin ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Otitis Media ◽  
Chronic Otitis Media ◽  
Substantial Variation ◽  
Treatment Methods ◽  
Group A ◽  
Group B ◽  
Ear Drops

Objective: To compare the efficacy of topical ciprofloxacin alone, versus a combination therapy ofsystemic with topical ciprofloxacin(0.6%) in achieving dry ears in active mucosal chronic otitis media after two weeks of treatment. Methods: After obtaining permission from ethical committee of Hospital, an over-all of 150 patients (with 75 subjects each, divided into two groups) were included in this study. In Group-A: Topical Ciprofloxacin ear drops (0.6%) 3-4 drops were instilled three times a day, 8 hours apart for 2 weeks. In Group-B: Tab Ciprofloxacin 500mg was given twice a day, 12 hours apart for 14 days along with topical Ciprofloxacin ear drops (0.6%) 3 drops were used thrice a day, 8 hours apart for 14 days. Results: Patients ranged between 15-45 years of age. Mean age of the patients was 30.3±7.4 and 29.2±7.7 years. In group-A, there were 41 males (54.7%) and in group-B 49 males (65.3%). Females were 34 (45.3%) in group-A and 27 (36%) in Group-B. Mean duration of ear discharge was 5.3±1.1 months in group-A while 5.5±1.4 months in Group-B. We could not find any substantial variation among the two group in terms of efficacy (p=0.249). Stratification with regard to age, gender and duration of ear discharge was also carried out. Conclusion: Results of this study showed that topical ciprofloxacin ear drops (0.6%) were equally effective as systemic ciprofloxacin combined with topical ciprofloxacin (0.6%), for treating chronically discharging ears. Keywords: CSOM, ciprofloxacin, nature of discharge

scholarly journals Adjuvant chemotherapy is an additional option for locally advanced gastric cancer after radical gastrectomy with D2 lymphadenectomy: a retrospective control study

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Lei Chen ◽  
Chenghai Zhang ◽  
Zhendan Yao ◽  
Ming Cui ◽  
Jiadi Xing ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Radical Gastrectomy ◽  
D2 Lymphadenectomy ◽  
D2 Gastrectomy ◽  
Group A ◽  
Group B

Abstract Background This study compared the long-term efficacy of different durations of adjuvant chemotherapy for patients with gastric cancer after radical gastrectomy with D2 lymphadenectomy. Methods We retrospectively identified 428 patients with stage II–III gastric cancer who underwent D2 gastrectomy between 2009 and 2016. Patients were divided into four groups according to the duration of adjuvant chemotherapy, including 0 week (no adjuvant, group A), 20 to 24 weeks (completed 7–8 cycles every 3 weeks or 10–12 cycles every 2 weeks, group B), and 12 to18 weeks (completed 4–6 cycles every 3 weeks or 6–9 cycles every 2 weeks, group C), and less than 12 weeks (received up to 3 cycles every 3 weeks or 5 cycles every 2 weeks, group D). The chemotherapy regimens included XELOX, SOX, and FOLFOX. 5-year overall survival (OS) and disease-free survival (DFS) were analyzed. Results The 5-year OS rates for groups A, B, C, and D were 52.3, 73.7, 72.0, and 53.3%, respectively, and the 5-year DFS rates were 50.0, 68.0, 65.4, and 50.0%, respectively. OS and DFS were higher in group B than in groups A and D. Similarly, patients in group C were more likely to have higher OS and DFS than those in groups A and D. Meanwhile, there were no significant differences in OS and DFS between groups B and C. The multivariate analysis confirmed with high statistical significance the efficacy of complete courses of adjuvant chemotherapy, and, among them, the similar impact of 4–6/6–9 and 7–8/10–12 cycles, resulting in similar HRs vs Group A (0.52 and 0.42, respectively). Conclusions To reduce toxicity and maintain efficacy, XELOX or SOX chemotherapy regimens administered for 4–6 cycles every 3 weeks or FOLFOX regimen for 6–9 cycles every 2 weeks might be a favorable option for patients with stage II–III gastric cancer after D2 gastrectomy. Prospective multicenter clinical trials with adequate sample sizes are necessary to verify these findings.

A prospective, randomized, controlled, multicenter study of apatinib combined with S-1 plus docetaxel as adjuvant therapy for locally advanced gastric cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16019-e16019
Author(s):  
Zhili Shan ◽  
Feng Guo ◽  
Hong Chen ◽  
Dapeng Li ◽  
Zhongqi Mao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Advanced Gastric Cancer ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Free Survival ◽  
Randomized Controlled ◽  
Locally Advanced Gastric Cancer ◽  
Group A ◽  
Group B ◽  
Disease Free

e16019 Background: Postoperative adjuvant chemotherapy is commonly given after the curative resection of gastric cancer (GC) in both Eastern and Western countries. Several studies have investigated the feasibility and safety of S-1 plus docetaxel or S-1 plus cisplatin. However, the best choice of adjuvant treatment for patients with gastric cancer is still debated. Apatinib, an oral small molecular of VEGFR-2 TKI, has been confirmed to improve OS and PFS with acceptable safety profile in patients with advanced gastric cancer refractory to two or more lines of prior chemotherapy. In this study, we aimed to evaluate the efficacy and safety of apatinib combined with S-1/docetaxel for locally advanced gastric cancer (T3-4aN+M0). Methods: This is a prospective, randomized, controlled, multicenter clinical study. Patients with locally advanced gastric cancer, pathological stage T3-4aN+M0 who underwent D2 lymphadenectomy without prior anti-cancer therapy were included. All these patients were assigned to group A or B. Patients in group A received 6 cycles (21 days a cycle) of adjuvant therapy using S-1 (80-120mg/d, d1-14), and docetaxel (40mg/m2, d1). Group B received the same regimen with the addition of apatinib (250mg, qd.). The primary endpoint was disease-free survival (DFS). The final analysis cutoff date was 30 November, 2020. Results: A total of 45 patients were enrolled from January 2019 to November, 2010 and assigned to group A (21) or group B (24). The DFS was not reached in both of the groups. The 1-year disease-free survival rate was 60% in group A and 90% in the group B, while the difference was not significant. The main AEs in group A were anemia (55%), nausea (50%) and neutropenia (40%); The most common AEs in group B were anemia (45%) neutropenia (40%) and diarrhea (25%). There were no treatment-related deaths. The longest administered time of apatinib with no progression was 457 days. And the median time to receive apatinib was 329 days. Conclusions: Combination of apatinib with S-1/docexal chemotherapy shows clinical benefits in locally advanced gastric cancer (T3-4aN+M0), with tolerable toxicity. The study is still ongoing to reach our final endpoint, DFS. Clinical trial information: ChiCTR2000038900.

Combination Therapy Of Tadalafil And Pentoxifylline In Severe Erectile Dysfunction; A Prospective Randomized Trial

2015 ◽  
Vol 87 (8) ◽  
Author(s):  
Santosh Kumar ◽  
Rajesh Roat ◽  
Swati Agrawal ◽  
Kumar Jayant ◽  
Ravimohan S. Mavuduru ◽  
...  
Keyword(s):  
Erectile Dysfunction ◽  
Combination Therapy ◽  
Erectile Function ◽  
T Test ◽  
P Value ◽  
Chi Square ◽  
Significant Difference ◽  
Chi Square Test ◽  
Group A ◽  
Group B

Abstractwas to assess efficacy of Tadalafil alone versus Tadalafil plus Pentoxifylline in the treatment of erectile dysfunction by using self administered IIEF-5 questionnaire.Two hundred and thirty seven patients presenting with ED at andrology OPD were evaluated for ED by a self administered IIEF (International Index of Erectile Function) questionnaire. Patients were systematically randomized by computer generated random table into two groups groups namely, group A: Tadalafil only group, group B: combination of Tadalafil + Pentoxifyl-line. All the patients were re-assessed by IIEF-5 questionnaire after 8 weeks of medical therapy. Statistical analysis was performed using student’s unpaired t-test, paired t-test, chi square test. p-value < 0.05 was considered statistically significant.Two hundred and thirty seven patients were included in the present study, in group A: 92 patients (78.6%) showed improvement in their IIEF score after 8 weeks of tadalafil treatment. While in group B, overall 104 patients(86.6%) showed improvement after combination of Tadalafil and Pentoxifylline. There was a statistically significant difference of percentage change in IIEF score was seen in group B (group A 90.7±15.2%, group B 95.6±13.4%; p value – 0.014). We found this difference even more statistically significant in patients with severe ED (group A 72.7±47.2%, group B 132.3±54.3%; p value – 0.000). There was no significant difference in between the two groups with regards to occur-rence of side effects.Both tadalafil and combination of Tadalafil + Pentoxifylline improve erectile function in patients of ED. Patients with severe ED showed much significant improvement in erectile function with combination therapy.

Gene Expression Reveals Two Distinct Biological Groups within T-Cell Prolymphocytic Leukaemia.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4366-4366
Author(s):  
Nnenna Osuji ◽  
Ilaria Del Giudice ◽  
Tim Dexter ◽  
Estella Matutes ◽  
Vasantha Brito-Babapulle ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
Chromosome 8 ◽  
Rt Pcr ◽  
Double Positive ◽  
Reciprocal Translocations ◽  
Prolymphocytic Leukemia ◽  
Group A ◽  
Differential Responses ◽  
Group B

Abstract T-cell prolymphocytic leukemia (T-PLL) is rare and presents with widespread disease. Indolent presentations are seen but eventually progress. The disease shows marked chemoresistance and is best treated with the monoclonal anti-CD52 antibody (CAMPATH). Prolymphocytes show a post-thymic phenotype and are CD4+CD8− (65%), CD4−CD8+ (10%) or CD4+CD8+ (25%). This double positive phenotype, raises questions about the putative ontology of T-PLL. Morphological heterogeneity, with typical (75%), small cell (20%) and cerebriform/sezary-like variants (5%) is described. Inversions or reciprocal translocations of chromosome 14 involving breakpoints at q11 (TCR a/d) and q32.1 (TCL1 and TCL1b) are seen (~ 80%). Other common abnormalities involve chromosome 8, translocation (X;14)(q28;q11) and, ATM (11q23). We investigated the clinico-pathological heterogeneity in T-PLL, at the level of the transcriptome and evaluated the ability of gene expression profiling to sub-classify T-PLL. Total RNA was extracted from blood prolymphocytes (>92% purity) of 22 patients. cDNA synthesis followed by biotin-labelled cRNA synthesis was carried out as per Affymetrix protocols. Fragmented cRNA was hybridized to the Human U133 PLUS2 GeneChip array (54K probes). Microarray services were provided by MRC geneservice (UK HGMP Resource Centre). Hierarchical clustering of samples was performed using a filtered gene set (12,456) and >4 different algorithims. Prediction analysis for micoarray (PAM) and significance analysis of microarray (SAM) were used to evaluate class performance, and partition genes using pre-defined labels of immunophenotype, karyotype, response and morphology. Validation was performed by RT-PCR in a subset of genes.Unsupervised analysis robustly and reproducibly partitioned samples into 2 groups; A (n=8) and B (n=14). SAM analysis identified 4487 differentially expressed transcripts (false discovery rates <1%), >40% of which showed >2-fold difference in expression between the groups. There was no statistical difference in age, immunophenotype or karyotype betweeen groups, however, differential response to CAMPATH was seen. PAM analysis refined a sub-group of ~123 genes which most efficiently differentiated these groups. Group A showed significantly higher rates of non-response and progressive disease as compared to group B (n=14, p=0.036). Key differences related to apoptosis and cell-cycle associated gene expression. Down regulation of caspases (CASP1, CASP2,CASP4, CARD8 and CASP8AP2), cyclins (CCNC, CCND2, CCND3, CCNG1, CCNI, CCNT2), bcl-2, HDAC1, HIPK2, IL6R and ATM were frequent in group A with upregulation of genes implicated in NF-kB (TRAF4, SQSTM1) and TNF pathways (LMNA, ARTS-1), as well as transcription factors such as ATF-3. CD52 expression was ~2-fold higher in group B and may explain in part, differential responses to CAMPATH. RT-PCR validated gene expression data for LMNA and ATF-3. Despite the small numbers, algorithim-independent segregation into 2 consistent groups, in conjunction with the magnitude of gene differences, presence of many mutually exclusive divisions, and low prediciton errors, imply that the 2 identified profiles arise from fundamental differences at a regulatory level and thus likely represent a generalisable classification for T-PLL. Differential responses to CAMPATH may be a sub-feature of this grouping.

The advantages of circular stapling instrument compared with Albert-Lembert suture for anastomosis of Billroth I gastrectomy for gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14104-14104
Author(s):  
H. Imamura ◽  
H. Furukawa ◽  
M. Tatsuta ◽  
T. Kishimoto ◽  
K. Yamamoto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Anastomotic Leakage ◽  
Distal Gastrectomy ◽  
Circular Stapler ◽  
Purse String ◽  
Billroth I ◽  
Anastomotic Bleeding ◽  
Group A ◽  
Group B ◽  
Linear Cutter

14104 Background: In Japan, reconstruction with Billroth I using Albert-Lembert suture had been usually performed in distal gastrectomy for gastric cancer. However stapling instruments have within recent years gained wide acceptance not only in total gastrectomy but also in distal gastrectomy. We have introduced circular stapling instrument for anastomosis reconstructed with Billroth I since June 2001. Methods: 111 and 222 patients with gastric cancer underwent distal gastrectomy reconstructed with Billroth I using Albert-Lembert suture from June 1999 to May 2001 (Group A) and using circular stapling instrument from June 2001 to December 2003 (Group B) for anastmosis in our institute, respectively. Albert-Lembert suture was performed as end-to-end gastroduodenostomy followed by resection of proximal line stapled across with liner cutter instrument. The procedure of anastomosis using circular stapling instrument was as followed; the distal duodenum was clamped with the purse-string instrument, divided proximally, the anvil was attached, the purse-string was tied down, the circular stapler without anvil was inserted through a gastrotomy, brought out through a stab wound at the anastomosis site, the instrument was closed and fired, and gastrectomy involving the site of gastrotomy was closed with linear cutter instrument. The followed-up periods of all patients from surgery were more than 2 years. We retrospectively compared the incidence of anastomosis-related complications within 2 years from surgery consisting of anastomotic bleeding, leakage, and stenosis. P-values were calculated statistically using χ2-test. Results: Anastomotic bleeding occurred in 1 (0.45%) patient of Group B, but in none of Group A (P=0.48). Anastomotic leakage occurred in 2 patients (1.80%) of Group A, but in none of Group B (P=0.045). Anastomotic stenosis occurred in 2 patients (0.90%) of Group B, but in none of Group A (P=0.32). All complications were recovered and all patients left hospital in the safety. Conclusions: Our data indicated that circular stapling instrument for anastomosis of Billroth I gastrectomy for gastric cancer significantly reduced the incidence of anastomotic leakage compared with Albert-Lembert suture. No significant financial relationships to disclose.

Characterization of human skeletal muscle in weight-losing pancreatic cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9571-9571
Author(s):  
J. M. Brell ◽  
J. Hardacre ◽  
J. Schulak ◽  
R. Onders ◽  
T. Stellato ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Weight Loss ◽  
Body Mass ◽  
Caspase 3 ◽  
Expression Patterns ◽  
Rt Pcr ◽  
Group A ◽  
Median Weight Loss

9571 Background: Decreased body mass (cachexia) is a common cause of functional decline in pancreas carcinoma (PC) and other malignancies. The etiology is unknown. Characterization of human PC skeletal muscle, in regard to proteolysis and gene expression, compared to control muscle may reveal information about pathophysiology. Methods: Biopsies of rectus abdominus muscle were performed in weight-losing PC patients all stages (A) during cancer-related surgery and in cancer-free controls undergoing ventral hernia repair (B). Caspase-3, pAkt, and urinary 3-methylhistidine (u3-MH) were assessed by Western blot and high-performance liquid chromatography. Fat-free mass (FFM), body mass index (BMI), and time to progression were recorded. Muscle from five patients (median weight loss 21%) and five controls were analyzed for gene expression patterns using Affymetrix Human Genome U133 A 2.0 array chip. Two hundred differentially over- and under-expressed genes were examined in group A for potential association with cachexia. RT-PCR confirmation of six candidate genes was performed. Results: Thirty-eight patients were enrolled. Median weight loss in group A (N=27) was 14.5% (5% - 34%). No differences were noted between groups in caspase-3 and pAkt expression. Baseline u3-MH (p=0.86) and FFM (p= 0.28) did not differ; baseline BMI was lower in group A (p=0.04). BMI follow-up measurements (N=17) were significantly decreased (p=0.0005). In 65% patients, progressive disease was noted within median time of 3 months. RT-PCR established up-regulation of CHRNA1 and LMO7, but not GDF8. mRNA down-regulation for TRIM63, IGF-BP6, and MYH-1 was confirmed. Conclusions: Muscle proteolysis in human PC skeletal muscle was not demonstrated, perhaps due to unmeasurable proteolysis or use of non-informative endpoints. BMI decreased in group A with PD; further studies need tight control of BMI variables. New hypotheses about cachexia include neuromuscular junction dysfunction, as CHRNA1 has specific role in ion channel gating; this is disrupted in the paraneoplastic Eaton-Lambert syndrome. This is first study analyzing human muscle in weight-losing PC and proves symptom management multidisciplinary research is feasible in academic setting. Supported by American Cancer Society pilot grant. No significant financial relationships to disclose.

Transcriptional characterization of microenvironment and their prediction role for the prognosis of hepatocellular carcinoma after surgery.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15650-e15650
Author(s):  
Kehe Chen ◽  
Haiming Wei ◽  
Tianqi Liu ◽  
Zhenxiang Chen ◽  
Deng Pan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Antigen Processing ◽  
Tissue Samples ◽  
Ffpe Tumor ◽  
Group A ◽  
One Year ◽  
Group B ◽  
Immune Related Genes ◽  
The Impact

e15650 Background: Hepatocellular carcinoma (HCC) is one of the most common prevalent fatal cancers worldwide with poor prognosis due to high incidence of recurrence. For patients with HCC, surgical treatment is a potentially cutative therapy. However, the puzzle in the therapy was the rapid recurrence after surgery. The purpose of this study was to integrate the impact of different immune context present in HCC microenvironment on patients’ prognosis, provide the molecular prediction clue of HCC recurrence. Methods: RNA targeted sequencing was performed on 12 primary tumor specimens from HCC patients. Transcripts of 395 immune related genes expressed in FFPE tumor samples were analyzed. The lima package was used to analyze the different expressed genes (DEGs) between patients with different prognosis. The gene set variance analysis (GSVA) analysis was performed to explore gene sets enrichment related to the recurrence post-resection. Results: 15 DEGs were detected in tissue samples between the two groups (group A: patients who relapsed within one year after surgery; group B: patients who hadn't relapsed beyond two years after surgery). The Antigen processing pathway enrichment may associate with the favorable prognosis (p < 0.05). HLA-A gene expression in group A was lower than that in group B; The gene expression of IL23A, TP63, ALOX15B, BUB1, CXCR2, CCL20, CLEC4C, PTK7, MPO, IL1B, MMP9, GAGE2C, GAGE2A, GAGE2E, DMBT1, FOXM1 in group A was higher than that in group B. Additionally, the combination of 3 genes (TP63, IL23A and BUB1) can distinguish the patients recurrent within 1 year or beyond 2 years post-resection. The joint diagnostic equation is logit (Y = 1) = 0.073 +0.740 *(TP63) + 0.589 * (IL23A)+0.959(BUB1), (Optimal threshold: 0.667, specificity: 1, sensitivity: 0.833). Conclusions: Our results suggest that RNA-seq of immune related genes from FFPE sample can effectively profile the specific landscape of tumor immune microenvironment and predict the survival of HCC. 3 genes’ expression (TP63, IL23A and BUB1) might correlate with recurrence in HCC patients after surgery.

Calcium dobesilate and oxerutin: effectiveness of combination therapy

2010 ◽  
Vol 25 (2) ◽  
pp. 66-71 ◽  
Author(s):  
B Akbulut
Keyword(s):  
Combination Therapy ◽  
Venous Insufficiency ◽  
Statistical Significance ◽  
Symptomatic Relief ◽  
Antioxidant Properties ◽  
Erythrocyte Aggregation ◽  
Calcium Dobesilate ◽  
Significant Difference ◽  
Group A ◽  
Group B

Objectives Chronic venous insufficiency (CVI) is an important cause of discomfort and inability to work. Hydroxyethylrutosides (Venoruton®; 0-[beta-hydroxyethyl]-rutosides) has been used for decades for the treatment of CVI. Studies have reported symptomatic relief and a decreased capillary filtration after the administration of the oral preparations. Calcium dobesilate is a synthetic venoactive drug acting on several levels. It inhibits capillary permeability; it has antioxidant properties; and it inhibits the synthesis of prostaglandins and thromboxanes, reducing platelet and erythrocyte aggregation, as well as blood viscosity. The aim of this study is to determine whether the combination of both drugs is more effective in decreasing patients' complaints. Methods One hundred and fifty patients with primary venous insufficiency were randomized into three groups: Group A receiving calcium dobesilate only, Group B receiving oxerutin only and Group C receiving both calcium dobesilate and oxerutin. Patients were evaluated with a questionnaire before and four weeks after treatment regarding following parameters: itching, fatigue, heaviness, numbness, cramp, swelling and sensitiveness. Patients rated their symptoms from 0 to 4 (0: absent; 1: mild; 2: moderate; 3: severe; 4: very severe). Results Complaints, which were scored by patients before and after treatment, decreased. Among the single-drug groups, itching score decreased more in Group B, whereas scores of fatigue, heaviness, numbness, cramp and swelling decreased more in Group A. But the difference was not significant, statistically. But all complaints decreased significantly in Group C. Difference of scores after treatment revealed no statistical significance in Group A and B, but scores of Group C produced a significant difference when compared with Group A and B. Conclusion Results demonstrate that a combination of calcium dobesilate and oxerutin shows a better improvement of complaints. These observations have to be confirmed in larger series with objective tests. Changes of quality of life after a combination therapy might also be of interest.

scholarly journals Null Mutations of Group A Streptococcus Orphan Kinase RocA: Selection in Mouse Infection and Comparison with CovS Mutations in Alteration of In Vitro and In Vivo Protease SpeB Expression and Virulence

2016 ◽  
Vol 85 (1) ◽  
Author(s):  
Wenchao Feng ◽  
Dylan Minor ◽  
Mengyao Liu ◽  
Jinquan Li ◽  
Suzanne L. Ishaq ◽  
...  
Keyword(s):  
Gene Expression ◽  
Growth Phase ◽  
Virulence Genes ◽  
Expression Patterns ◽  
Mouse Skin ◽  
Exponential Growth Phase ◽  
Wild Type ◽  
Subcutaneous Infection ◽  
Group A

ABSTRACT Group A Streptococcus (GAS) acquires mutations of the virulence regulator CovRS in human and mouse infections, and these mutations result in the upregulation of virulence genes and the downregulation of the protease SpeB. To identify in vivo mutants with novel phenotypes, GAS isolates from infected mice were screened by enzymatic assays for SpeB and the platelet-activating factor acetylhydrolase Sse, and a new type of variant that had enhanced Sse expression and normal levels of SpeB production was identified (the variants had a phenotype referred to as enhanced Sse activity [SseA+] and normal SpeB activity [SpeBA+]). SseA+ SpeBA+ variants had transcript levels of CovRS-controlled virulence genes comparable to those of a covS mutant but had no covRS mutations. Genome resequencing of an SseA+ SpeBA+ isolate identified a C605A nonsense mutation in orphan kinase gene rocA, and 6 other SseA+ SpeBA+ isolates also had nonsense mutations or small indels in rocA. RocA and CovS mutants had similar levels of enhancement of the expression of CovRS-controlled virulence genes at the exponential growth phase; however, mutations of RocA but not mutations of CovS did not result in the downregulation of speB transcription at stationary growth phase or in subcutaneous infection of mice. GAS with RocA and CovS mutations caused greater enhancement of the expression of hasA than spyCEP in mouse skin infection than wild-type GAS did. RocA mutants ranked between wild-type GAS and CovS mutants in skin invasion, inhibition of neutrophil recruitment, and virulence in subcutaneous infection of mice. Thus, GAS RocA mutants can be selected in subcutaneous infections in mice and exhibit gene expression patterns and virulences distinct from those of CovS mutants. The findings provide novel information for understanding GAS fitness mutations in vivo, virulence gene regulation, in vivo gene expression, and virulence.

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