scholarly journals Efficacy of Clarithromycin Depends on the Bacterial Density in Clarithromycin-Heteroresistant Helicobacter pylori Infections: An In Situ Detected Susceptibility and Quantitative Morphometry-Based Retrospective Study

2021 ◽  
Vol 27 ◽  
Author(s):  
Jewel Ju Ea Kim ◽  
Ildikó Kocsmár ◽  
György Miklós Buzás ◽  
Ildikó Szirtes ◽  
Orsolya Rusz ◽  
...  

The global rise in clarithromycin (Cla) resistance is considered to be the main contributor of Helicobacter pylori (Hp) eradication failures. In nearly half of the Cla-resistant Hp infections, Cla-susceptible bacteria are simultaneously present with the Cla-resistant ones (Cla-heteroresistance). The proportion of resistant bacteria in the bacterial population (R-fraction) and its predictive role for the use of Cla-based therapies in Cla-heteroresistant infections has not yet been investigated. Our retrospective study analyzed gastric biopsy samples of 62 Hp-positive patients with Cla-heteroresistant infection. Fluorescence In Situ Hybridization technique was used to visualize the coexistence of resistant and susceptible bacteria within one tissue sample. R-fraction was quantified on multichannel microimages by digital morphometry. Resistant bacteria had a patchy distribution within the whole bacterial population causing high diversity among the investigated areas. Patients were subdivided into two major groups according to whether a Cla-based eradication attempt was conducted before or after the biopsy sampling. R-fraction was significantly lower among cases having only one previous Cla-based eradication attempt vs. those that had multiple previous eradications, including at least one Cla-containing therapy (0.41 vs. 0.89, p = 0.0308). Majority of the patients without previous eradication attempt had successful eradication with Cla-containing regimen (59.26%), verified by a negative 13C-urea breath test or control biopsy. Multivariable model indicated that the therapeutic outcome using Cla-based regimens depended on the bacterial density rather than the R-fraction. Our study raises the potential use of Cla-containing eradication therapies in certain Cla-heteroresistant Hp infections, taking into account the possible predictive role of bacterial density.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Éva Kocsmár ◽  
György Miklós Buzás ◽  
Ildikó Szirtes ◽  
Ildikó Kocsmár ◽  
Zsófia Kramer ◽  
...  

AbstractClarithromycin is a macrolide antibiotic widely used for eradication of Helicobacter pylori infection, and thus resistance to this antibiotic is a major cause of treatment failure. Here, we present the results of a retrospective observational study of clarithromycin resistance (Cla-res) in 4744 H. pylori-infected patients from Central Hungary. We use immunohistochemistry and fluorescence in situ hybridization on fixed gastric tissue samples to determine H. pylori infection and to infer Cla-res status, respectively. We correlate this information with macrolide dispensing data for the same patients (available through a prescription database) and develop a mathematical model of the population dynamics of Cla-res H. pylori infections. Cla-res is found in 5.5% of macrolide-naive patients (primary Cla-res), with no significant sex difference. The model predicts that this primary Cla-res originates from transmission of resistant bacteria in 98.7% of cases, and derives from spontaneous mutations in the other 1.3%. We find an age-dependent preponderance of female patients among secondary (macrolide-exposed) clarithromycin-resistant infections, predominantly associated with prior use of macrolides for non-eradication purposes. Our results shed light into the sources of primary resistant cases, and indicate that the growth rate of Cla-res prevalence would likely decrease if macrolides were no longer used for purposes other than H. pylori eradication.


2019 ◽  
Vol 51 (3) ◽  
pp. 910-918
Author(s):  
Sung Han Kim ◽  
Boram Park ◽  
Jae Young Joung ◽  
Jinsoo Chung ◽  
Ho Kyung Seo ◽  
...  

1993 ◽  
Vol 13 (1) ◽  
pp. 135-144 ◽  
Author(s):  
Tomohiro Matsuyama ◽  
Hisamasa Michishita ◽  
Hitoshi Nakamura ◽  
Masato Tsuchiyama ◽  
Souichiro Shimizu ◽  
...  

To assess the role of Cu-Zn superoxide dismutase (CuZnSOD) in regulating cellular antioxidant defenses, we studied the induction of CuZnSOD mRNA by an in situ hybridization technique and of CuZnSOD protein by an immunocytochemical method in the gerbil hippocampus following 5 min of transient global ischemia. For hybridization, we synthesized 48-mer oligonucleotide (base 465–512) complementary to rat CuZnSOD mRNA. Northern blot analysis showed hybridization to a single band of molecular weight 0.65 kb. After 5 min of ischemia, the signal became stronger at 3 and 24 h and returned to the control level 3 days later. In situ hybridization histochemistry revealed an increase in labeling throughout the hippocampus, especially in the granular layer 3 h following ischemia. The increase was prolonged only in the CA1 pyramidal layer after 24 h and was eliminated within 3 days or later. Conversely, analysis by Western blotting revealed that the insult produced few effects on the induction of CuZnSOD protein. Immunocytochemistry for CuZnSOD revealed a reduced immunostaining in the CA1 pyramidal layer at 24 h of recirculation when the persistent expression of CuZnSOD mRNA was shown in the same area. Our findings suggest that the expression of endogenous CuZnSOD is temporarily stimulated by an ischemic insult without increasing the protein level. The prolonged increase in mRNA and the decrease in the protein of CuZnSOD in the CA, neurons seem to imply an important role of the endogenous antioxidant enzyme that protects against the detrimental effects of superoxide radicals on delayed neuronal death.


2018 ◽  
Author(s):  
Ana Roguljic ◽  
Gulio Spagnoli ◽  
Antonio Juretic ◽  
Bozena Sarcevic ◽  
Marija Banovic ◽  
...  

Author(s):  
Gabriel Levin ◽  
Shmuel Herzberg ◽  
Uri P. Dior ◽  
Asher Shushan ◽  
Ronit Gilad ◽  
...  

2021 ◽  
Author(s):  
Samia Alaoui Boukhris ◽  
Mounia El khadir ◽  
Safae Karim ◽  
Tiatou Souho ◽  
Dafr-Allah Benajah ◽  
...  

Abstract Purpose: Helicobacter pylori, Epstein-Barr virus and human papillomavirus are three pathogens associated with various human cancers. This study aimed to investigate the role of these pathogens in gastric cancer in Moroccan population Methods: For this, a retrospective study has been conducted on participants attending the gastroenterology department of Hassan II University Hospital of Fez. A total of 279 participants were enrolled. H. pylori, EBV and HPV were detected and genotyped by PCR.Results: A significant association has been established between H. pylori, EBV and gastric cancer. 93.4% and 43.3% of gastric cancer cases are related to H. pylori and EBV respectively (p≤0.01). H. pylori-EBV co-infection is responsible of 31.6% of gastric cancer cases (p<0.01). Correlation between pathogens genotypes and gastric cancer shows 55.6% of GC EBV positives are carrying the 30bp deletion in LMP1gene, while 16% of gastric cancers cases are carrying high-risk genotypes of HPV (p=0.21). Conclusion: The obtained results highlight the possible role of co-infection in gastric cancer development.


2005 ◽  
Vol 85 (3) ◽  
pp. 195-203 ◽  
Author(s):  
XULIO MASIDE ◽  
STAVROULA ASSIMACOPOULOS ◽  
BRIAN CHARLESWORTH

We have investigated at the molecular level four cases in which D. melanogaster middle repetitive DNA probes consistently hybridized to a particular band on chromosomes sampled from a D. melanogaster natural population. Two corresponded to true fixations of a roo and a Stalker element, and the others were artefacts of the in situ hybridization technique caused by the presence of genomic DNA flanking the transposable elements (TEs) in the probes. The two fixed elements are located in the β-heterochromatin (20A and 80B, respectively) and are embedded in large clusters of other elements, many of which may also be fixed. We also found evidence that this accumulation is an ongoing process. These results support the hypothesis that TEs accumulate in the non-recombining part of the genome. Their implications for the effects of TEs on determining the chromatin structure of the host genomes are discussed in the light of recent evidence for the role of TE-derived small interfering-RNAs as cis-acting determinants of heterochromatin formation.


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