Helicobacter pylori eradication: how can I choose an appropriate therapy?
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Antacids↗
Biomedical subjects
F Franceschi
Publications and source records attributed to F Franceschi.
Extragastric manifestations of Helicobacter pylori infection.
Since the discovery of Helicobacter pylory (H. pylori), several studies have been published concerning a hypothetical role of this bacterium in different extragastric diseases, such as ischemic heart disease, idiopathic thrombocytopenic purpura, iron deficiency anemia or other disorders. The majority of those studies may be classified as epidemiological or eradicating trials but there are also case reports or in vitro studies. Idiopathic thromobocytopenic purpura represents the disease showing a stronger link with H. pylori infection. There are also increasing evidences on the role of H. pylori infection in iron deficiency anemia and ischemic heart disease. On the contrary, the association between H. pylori infection and other diseases is still controversial, as is supported in the majority of the cases by case reports, small pilot studies or just in vitro data.
Anemia, Iron-Deficiency↗
Liver function evaluation in dogs by the galactose load test.
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Animals↗
Helicobacter pylori infection and ischaemic heart disease: an overview of the general literature.
In the last years, a considerable number of studies have been performed on the correlation between Helicobacter pylori infection and ischaemic heart disease. The reason is the supposed role of some chronic infections in the genesis and development of vessel wall injury and atheromatous plaque, as already reported for Chlamydia pneumoniae and herpes viruses. While this association may be theoretically conceivable, it still remains debated from a practical point of view. Epidemiological and animal studies as well as some eradicating trials gave conflicting results, while studies investigating the specific molecular mimicry mechanisms induced by H. pylori strongly support the association. Moreover, none of the studies performed so far did take into account the effect of the genetic susceptibility to develop ischaemic heart disease or to respond to H. pylori infection. In particular, while the exposure to some known risk factor for atherosclerosis should lead to develop ischaemic heart disease, no condition or exposure, either individual or in combination, completely explains the occurrence and the progression of the disease, as many patients develop ischaemic heart disease in the absence of any risk factor. Based on these concepts, can we state that H. pylori infection may cause the same effect in patients with ischaemic heart disease as in healthy subjects? Further studies are needed in order to clarify this issue.
Animals↗
Bacillus clausii therapy to reduce side-effects of anti-Helicobacter pylori treatment: randomized, double-blind, placebo controlled trial.
BACKGROUND: Helicobacter pylori eradication fails in about 10% of patients, particularly because of the occurrence of resistance to antibiotics and side-effects. During anti-H. pylori therapy, probiotics have been successfully used to reduce the incidence of side-effects. AIM: To evaluate the effect of Bacillus clausii, a probiotic, on incidence (primary variable) and severity of antibiotic-associated side-effects during anti-H. pylori therapy. METHODS: One hundred and twenty H. pylori-positive patients were randomly screened to receive: (i) a standard 7 days triple therapy with rabeprazole 20 mg b.d., clarithromycin 500 mg b.d. and amoxicillin 1 g b.d. and B. clausii t.d.s. (each preparation containing 2 x 10(9) spores) for 14 days starting from the first day of treatment. (ii) The same 7 days triple therapy and placebo t.d.s. for 14 days starting from the first day of treatment. Side-effects were assessed using a validated questionnaire and were recorded for 4 weeks from the start of therapy. RESULTS: The incidences of nausea, diarrhoea and epigastric pain in patients treated with B. clausii were significantly lower than in placebo group, in both PP and ITT analysis. Equally, intensity of nausea and diarrhoea in patients treated with B. clausii was significantly lower than in placebo group. There were no differences in adherence to treatment and H. pylori eradication rates between groups. Conclusion : In symptom-free, H. pylori-positive subjects B. clausii bacteriotherapy reduces the incidence of the most common side-effects related to anti-H. pylori antibiotic therapy compared with placebo.
2-Pyridinylmethylsulfinylbenzimidazoles↗
Helicobacter pylori test-and-treat strategy in the management of dyspepsia in primary care: an overview.
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Dyspepsia↗
Primary autoimmune haemolytic anaemia and coeliac disease.
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Adult↗
Macrolide resistance from the ribosome perspective.
Macrolides are important antibiotics used in treatment of respiratory tract infections in humans. Although some of these compounds have been in use for 50 years, it has not been until the last few years that their mechanism of action and the nature of ribosomal-based resistance could be more fully understood. With the advent of robust crystals of ribosomal 50S subunits, and structural resolution of macrolides and ketolides complexed to either Haloarcula marismortui or Deinococcus radiodurans 50S, the ability to dissect the binding modes and understand resistance at the level of the ribosome became possible. This review article compares the binding features of 14-, 15-, and 16-membered macrolides to that of ketolides telithromycin and ABT-773 as revealed at the atomistic level. Attempts to understand how modifications to 23S rRNA and/or mutations in ribosomal proteins L4 and L22 that have been found to confer resistance in Streptococcus pneumoniae, Streptococcus pyogenes, and Haemophilus influenzae are told from the perspective of the ribosome.
Animals↗
Isokinetic evaluation of anterior cruciate ligament reconstruction: quadriceps tendon versus patellar tendon.
AIM: The goal of this prospective randomized study was to compare the isokinetic recovery of thigh strength after anterior cruciate ligament (ACL) reconstruction by using patellar or quadriceps tendon as graft at the 6th month follow-up. METHODS: The authors evaluated 48 patients who underwent arthroscopic ACL reconstruction using patellar tendon (PT group) or quadriceps tendon (QT group) as autograft after a 6 months follow-up undergoing the following tests: the Ergojump Bosco System springboard and Universal's FITNET computerized isokinetic system. RESULTS: The counter movement jump (CMJ) test showed a 24% (p<0.01) strength deficit in patients operated with patellar tendon and 11% in the quadriceps tendon group. Also in the leg press test the greater differences in strength (p<0.05) were verified in the patellar tendon group, above all the peak torque (PT) test carried out at 3 repetitions (15%). CONCLUSIONS: The strength deficit found in the subjects operated with quadriceps tendon were statistically lower in comparison to that verified in the patellar tendon group. A good recovery in thigh strength after 6 months in patients operated with quadriceps tendon could encourage the use of this kind of graft in order to achieve an easier rehabilitation and a faster release of the patient to daily and sports activity.
Adult↗
[Mitral insufficiency related to a spasm of the left anterior descending artery. A case report].
We report the case of a female patient of 76 years old admitted to our hospital for a pre-operative assessment of a symptomatic mitral regurgitation (MR) whose transthoracic echocardiography revealed only a trivial regurgitation. The occurrence during hospital stay of an acute pulmonary edema contemporary to the occurrence of a huge MR permitted to suspect the diagnosis of a paroxystic ischemic MR. Angiographic and hemodynamic evaluation revealed only a non-significant atheromateous plaque located in the distal LAD. The infusion of Methylergometrine triggered a severe spasm at the site of that plaque, associated with a huge MR visualized by TTE with restricted movements of both leaflets, responsible for an acute pulmonary edema occurring on the table of the catheterization laboratory. Recovery was quickly obtained after intravenous injection of Nitroglycerin, which removed the spasm and valvular regurgitation. The diagnosis of paroxystic ischemic mitral regurgitation was confirmed and a treatment based on high dosage of calcium-blocker was decided. After a follow-up of more than one year, the patient remains asymptomatic and the regurgitation has never occurred.
Aged↗
Helicobacter pylori infection and expression of the angiogenic factor platelet-derived endothelial cell growth factor by pre-neoplastic gastric mucosal lesions and gastric carcinoma.
BACKGROUND: Expression of the angiogenic factor platelet-derived endothelial cell growth factor is induced in some gastric carcinomas. Whether angiogenesis is induced early in the development of gastric pre-neoplastic lesions and whether Helicobacter pylori infection affects platelet-derived endothelial cell growth factor expression is not known. AIM: To assess whether chronic gastritis, intestinal metaplasia, gastric dysplasia and gastric carcinomas express platelet-derived endothelial cell growth factor and whether Helicobacter pylori infection might affect the expression of platelet-derived endothelial cell growth factor in these lesions. PATIENTS AND METHODS: Patients with gastric carcinomas, atrophic gastritis with associated intestinal metaplasia, dysplasia and controls without infection or carcinoma were studied. RESULTS: Platelet-derived endothelial cell growth factor was detected by immunohistochemistry in 9 out 19 gastric carcinomas (45%). Only focal immunostaining was detected in intestinal metaplasia adjacent to dysplasia and in dysplastic cells. Of the tumours, 90% contained platelet-derived endothelial cell growth factor-positive interstitial cells. A significant correlation was found between active Helicobacter pylori infection and a larger number of platelet-derived endothelial cell growth factor-positive interstitial cells in areas of intestinal metaplasia (p<0.05). CONCLUSION: Helicobacter pylori infection does not influence the expression of platelet-derived endothelial cell growth factor, once gastric cancer has developed. However, Helicobacter pylori infection may increase the extension of expression of platelet-derived endothelial cell growth factor by infiltrating interstitial cells in premalignant lesions, such as intestinal metaplasia, which may help create a favourable environment for tumour development. This may possibly be due to non-specific increase in recruitment of inflammatory cells caused by Helicobacter pylori infection. Further studies, with a larger number of samples, are now needed in order to confirm this finding.
Adenocarcinoma↗
[Cardioversion by external electric shock for atrial fibrillation: does patient age affect immediate results?].
The restoration of sinus rhythm by external electric shock in patients with persistent atrial fibrillation is a well established treatment. However, in current practice this treatment is generally indicated less in the elderly subject although this attitude is not factual. The objective of this work was to evaluate the immediate results of cardioversion by external electric shock, comparing the success rates in four age groups: under 60 years, between 60 and 69 years, between 70 and 79 years, and over 80 years. This study was performed on 182 consecutive patients aged from 25 to 89 years: 35 patients aged less than 60 years, 52 patients aged from 60 to 69 years, 65 patients aged from 70 to 79 years, and 30 patients aged 80 years or over. The success rates were 91.4% before 60 years, 90.4% between 60 and 69 years, 90.8% between 70 and 79 years, and 83.3% after 80 years. There was no significant difference between the success rates in the four age groups (p = 0.68). Among the other factors analysed, only the duration of atrial fibrillation and the body mass index significantly influenced the results of external electric shock in this series. This work suggests that age does not significantly influence the immediate results of external electric shock. According to these data it does not appear justified to contra-indicate cardioversion by external electric shock on the sole criterion of age.
Adult↗
High resolution structure of the large ribosomal subunit from a mesophilic eubacterium.
We describe the high resolution structure of the large ribosomal subunit from Deinococcus radiodurans (D50S), a gram-positive mesophile suitable for binding of antibiotics and functionally relevant ligands. The over-all structure of D50S is similar to that from the archae bacterium Haloarcula marismortui (H50S); however, a detailed comparison revealed significant differences, for example, in the orientation of nucleotides in peptidyl transferase center and in the structures of many ribosomal proteins. Analysis of ribosomal features involved in dynamic aspects of protein biosynthesis that are partially or fully disordered in H50S revealed the conformations of intersubunit bridges in unbound subunits, suggesting how they may change upon subunit association and how movements of the L1-stalk may facilitate the exit of tRNA.
Bacterial Proteins↗
Structural basis for the interaction of antibiotics with the peptidyl transferase centre in eubacteria.
Ribosomes, the site of protein synthesis, are a major target for natural and synthetic antibiotics. Detailed knowledge of antibiotic binding sites is central to understanding the mechanisms of drug action. Conversely, drugs are excellent tools for studying the ribosome function. To elucidate the structural basis of ribosome-antibiotic interactions, we determined the high-resolution X-ray structures of the 50S ribosomal subunit of the eubacterium Deinococcus radiodurans, complexed with the clinically relevant antibiotics chloramphenicol, clindamycin and the three macrolides erythromycin, clarithromycin and roxithromycin. We found that antibiotic binding sites are composed exclusively of segments of 23S ribosomal RNA at the peptidyl transferase cavity and do not involve any interaction of the drugs with ribosomal proteins. Here we report the details of antibiotic interactions with the components of their binding sites. Our results also show the importance of putative Mg+2 ions for the binding of some drugs. This structural analysis should facilitate rational drug design.
Anti-Bacterial Agents↗
Metal-metal and carbon-carbon bonds as potential components of molecular batteries.
The reductive coupling of [M(salophen)] derivatives, where M is an early transition metal and salophen is N,N'-o-phenylenebis(salicylideneaminato) dianion, led to the formation of dimers linked through C-C and M-M bonds. Both of these bonds can potentially function as electron reservoirs: each bond can be used as a reversible source of a pair of electrons under the condition that it is not chemically transformed by the incoming substrate which functions as an electron acceptor. To explore this potential function as well as the competition in the redox processes between C-C and M-M bonds within the same molecular framework, we investigated the reduction of [(tBu4-salophen)NbCl3] (1) and [(tBu4-salophen)MoCl2] (7) as model compounds. In the former case, the reduction led to [(Nb-Nb)(tBu4-*salophen2*)] (2) which contains both a Nb-Nb bond (2.6528(7) A) and two C-C bonds across two imino groups of the ligand. Complex 2 can be reduced further to a transient compound 5 that contains an Nb=Nb bond. In the second case, the reduction of 7 by two electrons led to [(Mo[triplebond]Mo)(tBu4-salophen)2] (8), which does not contain any C-C linkages between the two salophen units. Complexes 2 and 5 are able to transfer one pair and two pairs of electrons, respectively, to give compounds 3, 4, and 6, with the consequent cleavage of the Nb-Nb and Nb=Nb bonds. In the present case, it is surprising that the C-C bonds do not participate in the reduction of the substrates. A careful theoretical treatment anticipates, both in the case of 1 and 7, the preferential formation of metal-metal bonds upon reduction. This is indeed the case for 7, but not for 1, where the formation of C-C bonds competes with that of M-M bonds, the latter being the first ones, however, to be involved in electron-transfer reactions. The theoretical approach allowed us to investigate the possibility of intramolecular electron transfer from C-C bonds to M-M bonds and vice versa.
Journal Article↗
Crystal structures of complexes of the small ribosomal subunit with tetracycline, edeine and IF3.
The small ribosomal subunit is responsible for the decoding of genetic information and plays a key role in the initiation of protein synthesis. We analyzed by X-ray crystallography the structures of three different complexes of the small ribosomal subunit of Thermus thermophilus with the A-site inhibitor tetracycline, the universal initiation inhibitor edeine and the C-terminal domain of the translation initiation factor IF3. The crystal structure analysis of the complex with tetracycline revealed the functionally important site responsible for the blockage of the A-site. Five additional tetracycline sites resolve most of the controversial biochemical data on the location of tetracycline. The interaction of edeine with the small subunit indicates its role in inhibiting initiation and shows its involvement with P-site tRNA. The location of the C-terminal domain of IF3, at the solvent side of the platform, sheds light on the formation of the initiation complex, and implies that the anti-association activity of IF3 is due to its influence on the conformational dynamics of the small ribosomal subunit.
Binding Sites↗
Reduction of dioxygen by a dimanganese unit bonded inside a cavity provided by a pyrrole-based dinucleating ligand.
A novel class of dinucleating ligands has been introduced into manganese chemistry to study the reactivity of this metal towards dioxygen under strictly controlled conditions. Such N4 ligands combine some of the major peculiarities of tetradentate Schiff bases and the porphyrin skeleton. They are derived from the condensation between 2-pyrrolaldehyde and ethylenediamine or o-phenylenediamine, leading to pyrenH2 (LH2, 1), pyrophenH2 (L'H2, 2) and Me2pyrophenH2, (L"H2, 3), respectively. Their metallation with [Mn3-(Mes)6] (Mes = 2,4,6-trimethylphenyl) led to [Mn2L2] (4), [MnL'(thf)2] (5) and [MnL"(thf)2] (6). Complex 4 displays a double-stranded helical structure, while 5 and 6 are mononuclear complexes containing hexacoordinated metals. Regardless of their structure, complexes 5 and 6 behave in a similar manner to 4 in their reaction with dioxygen, namely, as a dimetallic unit inside a cavity defined by two dinucleating ligands. These reactions led to dinuclear MnIII/MnIV oxo-hydroxo derivatives, [Mn2L2(mu-O)(mu-OH)] (7), [Mn2L'2(mu-O)(mu-OH)] (8) and [Mn2L"2(mu-O)(mu-OH)] (9), in which the two Mn ions are strongly antiferromagnetically coupled [J = -53 (7), J = -64 (8), J = -60 cm(-1) (9)]. The crystal structure of 7 could only be solved with synchrotron radiation as the crystals diffracted very poorly and suffered from twisting and disorder. The formation of 7-9 has been proposed to occur through the formation of an intermediate dinuclear hydroperoxo species.
Journal Article↗
Inducible ventricular arrhythmias and patency of infarct-related artery in survivors of acute myocardial infarction.
BACKGROUND: Patency of infarct-related artery in patients who suffered an acute myocardial infarction (AMI) has been shown to be associated with improved survival. Ventricular tachyarrhythmias induced by programmed electrical stimulation may be predictive of arrhythmic events and sudden death. HYPOTHESIS: The study was undertaken to assess the possible effect of a patent infarct-related coronary artery on induced ventricular tachyarrhythmias during programmed ventricular stimulation in survivors of AMI. METHODS: In this prospective study, programmed electrical stimulation was performed before hospital discharge (14 +/- 2 days) in 79 patients who survived an AMI. Patients were subdivided into two groups: Group I with patent infarct-related coronary artery (n = 64) and Group 2 with occluded infarct-related artery (n = 15) at coronary angiography performed at 14 +/- 2 days. These two groups were comparable in terms of mean left ventricular ejection fraction, location of infarct-related artery, number of diseased vessels, peak creatine kinase value, and infarct location. RESULTS: Ventricular arrhythmias were induced in 21 patients ( 32.6%) of Group I and 4 patients (26.6%) of Group 2. This difference was not statistically significant. CONCLUSION: This study suggests that ventricular arrhythmias induced by programmed ventricular stimulation in survivors of AMI did not differ whether the infarct-related artery was patent or occluded. Other factors may play a role in electrical instability as assessed by programmed ventricular stimulation.
Arrhythmias, Cardiac↗