Virulence factors predict long-term clinical efficacy of eradication therapy in nonulcer dyspepsia (NUD)

2000 ◽  
Vol 118 (4) ◽  
pp. A1326
Author(s):  
H.H-X Xia ◽  
N.J. Talley ◽  
A.L. Blum ◽  
C.A. O’Morain ◽  
E. Bolling-Stemevald
Keyword(s):  
Virulence Factors ◽  
Clinical Efficacy ◽  
Eradication Therapy ◽  
Nonulcer Dyspepsia

Clinical Efficacy of Dhatryadi Ghanavati in Shvitra (Vitiligo)

2017 ◽  
Vol 1 (4) ◽  
Author(s):  
Manjiri Walinjkar ◽  
P.D. Londhe ◽  
S. R. Makhare ◽  
Anil Avhad
Keyword(s):  
Clinical Efficacy ◽  
Skin Disorder ◽  
Total Population ◽  
Social Stigma ◽  
Term Treatment ◽  
Effective Therapy ◽  
Long Term Treatment ◽  
Percentage Area ◽  
Effective Remedy

Background: Shvitra (vitiligo) is a kind of skin disorder comprising of white coloured skin patches which is considered as a social stigma. Worldwide prevalence of Vitiligo is observed as 1% of the total population. Due to the chronic nature, long term treatment, lack of uniform effective therapy and unpredictable course the disease is usually very demoralizing for patients. Aim: To study the efficacy of ‘Dhatryadi Ghanavati’ in the management of Shvitra. Materials and Methods: Total 50 patients of Shvitra from OPD and IPD unit of Dr. M.N. Agashe Hospital, Satara were selected and provided with Dhatryadi Ghanavati 1gm B.D. for the duration of 3 months. Results: 100% relief was observed in Daha and Kandu followed by 83.33% relief was observed in Rukshata. 34.51% improvement was seen in number of patches, 34.82% in size of patches and 34.29% in percentage area involved. Color of the patches was improved by 69.01% whereas 44% improvement was seen in hair discoloration. Conclusion: The compound formulation ‘Dhatryadi Ghanavati’ was found as an effective remedy for ‘Shvitra’. The parameters like number of patches, size of patches, percentage area involved and colour of patches showed statistically highly significant results.

scholarly journals Pseudomonas aeruginosa PA80 is a cystic fibrosis isolate deficient in RhlRI quorum sensing

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Syed A. K. Shifat Ahmed ◽  
Michelle Rudden ◽  
Sabrina M. Elias ◽  
Thomas J. Smyth ◽  
Roger Marchant ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Genomic Islands ◽  
Clinical Strain ◽  
Whole Genome ◽  
Synonymous Mutations ◽  
Wide Range

AbstractPseudomonas aeruginosa uses quorum sensing (QS) to modulate the expression of several virulence factors that enable it to establish severe infections. The QS system in P. aeruginosa is complex, intricate and is dominated by two main N-acyl-homoserine lactone circuits, LasRI and RhlRI. These two QS systems work in a hierarchical fashion with LasRI at the top, directly regulating RhlRI. Together these QS circuits regulate several virulence associated genes, metabolites, and enzymes in P. aeruginosa. Paradoxically, LasR mutants are frequently isolated from chronic P. aeruginosa infections, typically among cystic fibrosis (CF) patients. This suggests P. aeruginosa can undergo significant evolutionary pathoadaptation to persist in long term chronic infections. In contrast, mutations in the RhlRI system are less common. Here, we have isolated a clinical strain of P. aeruginosa from a CF patient that has deleted the transcriptional regulator RhlR entirely. Whole genome sequencing shows the rhlR locus is deleted in PA80 alongside a few non-synonymous mutations in virulence factors including protease lasA and rhamnolipid rhlA, rhlB, rhlC. Importantly we did not observe any mutations in the LasRI QS system. PA80 does not appear to have an accumulation of mutations typically associated with several hallmark pathoadaptive genes (i.e., mexT, mucA, algR, rpoN, exsS, ampR). Whole genome comparisons show that P. aeruginosa strain PA80 is closely related to the hypervirulent Liverpool epidemic strain (LES) LESB58. PA80 also contains several genomic islands (GI’s) encoding virulence and/or resistance determinants homologous to LESB58. To further understand the effect of these mutations in PA80 QS regulatory and virulence associated genes, we compared transcriptional expression of genes and phenotypic effects with isogenic mutants in the genetic reference strain PAO1. In PAO1, we show that deletion of rhlR has a much more significant impact on the expression of a wide range of virulence associated factors rather than deletion of lasR. In PA80, no QS regulatory genes were expressed, which we attribute to the inactivation of the RhlRI QS system by deletion of rhlR and mutation of rhlI. This study demonstrates that inactivation of the LasRI system does not impact RhlRI regulated virulence factors. PA80 has bypassed the common pathoadaptive mutations observed in LasR by targeting the RhlRI system. This suggests that RhlRI is a significant target for the long-term persistence of P. aeruginosa in chronic CF patients. This raises important questions in targeting QS systems for therapeutic interventions.

scholarly journals Long-term outcomes of fully covered self-expandable metal stents versus plastic stents in chronic pancreatitis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sang Hoon Lee ◽  
Yeon Suk Kim ◽  
Eui Joo Kim ◽  
Hee Seung Lee ◽  
Jeong Youp Park ◽  
...  
Keyword(s):  
Chronic Pancreatitis ◽  
Clinical Efficacy ◽  
De Novo ◽  
Plastic Stents ◽  
Metal Stents ◽  
Plastic Stent ◽  
Sems Group ◽  
Spontaneous Migration

AbstractChronic pancreatitis (CP) related main pancreatic duct (MPD) stricture has been a challenge for endoscopists. Fully covered self-expandable metal stents (FC-SEMS) has been tried in CP patients, but the efficacy and safety are still controversial. Thus, we aim to compare the long-term clinical efficacy of FC-SEMS vs. plastic stent placement in persistent MPD strictures secondary to CP. Between 2007 and 2018, 80 chronic pancreatitis patients (58 males, median age 49 years), who underwent endoscopic placement of FC-SEMS (n = 26) and plastic stent (n = 54) for persistent MPD strictures after at least 3 months of initial single plastic stenting, were retrospectively analyzed during a median follow-up duration of 33.7 months. As a result, MPD stricture resolution rate was statistically higher in FC-SEMS group (87.0% vs. 42.0%, p < 0.001). Although immediate complications occurred similarly (38.5% vs. 37.0%, p = 0.902), spontaneous migration (26.9%) and de novo strictures (23.1%) were pronounced delayed complications in FC-SEMS group. Pain relief during follow-up was significantly higher in FC-SEMS group (76.9% vs. 53.7%, p = 0.046). The total procedure cost was similar in both groups ($1,455.6 vs. $1,596.9, p = 0.486). In comparison with plastic stent, FC-SEMS placement for persistent MPD strictures had favorable long-term clinical efficacy, with its typical complications like spontaneous migration and de novo strictures.

scholarly journals 149. Efficacy of Cochleated Amphotericin B (CAMB) in Mouse and Human Mucocutaneous Candidiasis

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S204-S205
Author(s):  
Jigar V Desai ◽  
Amanda Urban ◽  
Doris Z Swaim ◽  
Elise Ferre ◽  
Benjamin Colton ◽  
...  
Keyword(s):  
Amphotericin B ◽  
Clinical Improvement ◽  
Clinical Efficacy ◽  
Chronic Mucocutaneous Candidiasis ◽  
Vaginal Tissue ◽  
Dose Escalation Study ◽  
Fungal Burden ◽  
Mucocutaneous Candidiasis ◽  
Inherited Susceptibility

Abstract Background Candida albicans causes debilitating mucosal infections in patients with inherited susceptibility to chronic mucocutaneous candidiasis (CMC), often requiring long-term azole-based treatment. Due to increasing azole resistance, alternative treatments are desirable. Acquired resistance to amphotericin B (AMB) is rare but AMB use is limited by parenteral administration and nephrotoxicity. Cochleated AMB (CAMB) is a new oral formulation of AMB and thus an attractive option for oropharyngeal candidiasis (OPC), esophageal candidiasis (EC) and vulvovaginal candidiasis (VVC). We assessed the efficacy of CAMB in mouse models of OPC and VVC and in 4 patients with azole resistant CMC manifesting as OPC, EC or VVC. Methods Act1 -/- mice were infected with C. albicans in models of OPC and VVC and were treated once daily via oral gavage with CAMB or vehicle or intraperitoneal AMB-deoxycholate (AMBd) from day 1 through 4 post-infection (pi). At day 5 pi, the tongue or vaginal tissue was harvested to quantify fungal burden. Patients with azole resistant CMC enrolled in a phase 2A CAMB dose escalation study. The primary endpoint was clinical improvement at 2 weeks based on an efficacy scale, followed by optional extension for long-term suppression of CMC to assess safety and efficacy. Results CAMB-treated mice had significantly reduced tongue and vaginal tissue fungal burden compared to vehicle-treated mice, while they exhibited comparable fungal control relative to AMBd-treated mice. Among 4 CAMB-treated patients, 3 reached clinical efficacy by 2 weeks at a dose of 400 mg twice daily and one reached clinical efficacy at 200 mg twice daily. Three of 4 patients continued on the extension phase past 48 months with sustained clinical improvement of OPC and EC; patient #3 had relapse of esophageal symptoms at week 24 and was withdrawn from further study. Clinical response was not seen for onychomycosis or VVC. CAMB was safe and well-tolerated without renal toxicity. Conclusion Oral administration of CAMB in IL-17-signaling deficient mice resulted in reduced tongue and vaginal tissue fungal burden during mucosal C. albicans infections. A proof-of-concept clinical trial in humans with inherited CMC showed efficacy in OPC and EC with good tolerability and safety. Disclosures Benjamin Colton, PharmD, Merck (Shareholder)Pfizer (Shareholder) Ruying Lu, n/a, Matinas BioPharma Inc. (Employee)Matinas BioPharma Inc. (Employee, Shareholder) Theresa Matkovits, PhD, Matinas BioPharma (Employee, Shareholder) Raphael J. Mannino, n/a, Matinas BioPharma Inc. (Employee, Shareholder) Michail Lionakis, MD, ScD, Matinas BioPharma (Research Grant or Support)

scholarly journals Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study

Gut ◽  
2017 ◽  
Vol 67 (1) ◽  
pp. 28-35 ◽  
Author(s):  
Ka Shing Cheung ◽  
Esther W Chan ◽  
Angel Y S Wong ◽  
Lijia Chen ◽  
Ian C K Wong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Proton Pump Inhibitors ◽  
Proton Pump ◽  
Proportional Hazards Model ◽  
Absolute Risk ◽  
Eradication Therapy ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model

ObjectiveProton pump inhibitors (PPIs) is associated with worsening of gastric atrophy, particularly in Helicobacter pylori (HP)-infected subjects. We determined the association between PPIs use and gastric cancer (GC) among HP-infected subjects who had received HP therapy.DesignsThis study was based on a territory-wide health database of Hong Kong. We identified adults who had received an outpatient prescription of clarithromycin-based triple therapy between year 2003 and 2012. Patients who failed this regimen, and those diagnosed to have GC within 12 months after HP therapy, or gastric ulcer after therapy were excluded. Prescriptions of PPIs or histamine-2 receptor antagonists (H2RA) started within 6 months before GC were excluded to avoid protopathic bias. We evaluated GC risk with PPIs by Cox proportional hazards model with propensity score adjustment. H2RA was used as a negative control exposure.ResultAmong the 63 397 eligible subjects, 153 (0.24%) developed GC during a median follow-up of 7.6 years. PPIs use was associated with an increased GC risk (HR 2.44, 95% CI 1.42 to 4.20), while H2RA was not (HR 0.72, 95% CI 0.48 to 1.07). The risk increased with duration of PPIs use (HR 5.04, 95% CI 1.23 to 20.61; 6.65, 95% CI 1.62 to 27.26 and 8.34, 95% CI 2.02 to 34.41 for ≥1 year, ≥2 years and ≥3 years, respectively). The adjusted absolute risk difference for PPIs versus non-PPIs use was 4.29 excess GC (95% CI 1.25 to 9.54) per 10 000 person-years.ConclusionLong-term use of PPIs was still associated with an increased GC risk in subjects even after HP eradication therapy.

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