Haem oxygenase-1 dictates intrauterine fetal survival in mice via carbon monoxide

Pregnancy establishment implies the existence of a highly vascularized and transient organ, the placenta, which ensures oxygen supply to the fetus via haemoproteins. Haem metabolism, including its catabolism by haem oxygenase-1 (HO-1), should be of importance in maintaining the homeostasis of haemoproteins and controlling the deleterious effects associated with haem release from maternal or fetal haemoglobins, thus ensuring placental function and fetal development. We demonstrate that HO-1 expression is essential to promote placental function and fetal development, thus determining the success of pregnancy. Hmox1 deletion in mice has pathological consequences for pregnancy, namely suboptimal placentation followed by intrauterine fetal growth restriction (IUGR) and fetal lethality. These pathological effects can be mimicked by administration of exogenous haem in wild-type mice. Fetal and maternal HO-1 is required to prevent post-implantation fetal loss through a mechanism that acts independently of maternal adaptive immunity and hormones. The protective HO-1 effects on placentation and fetal growth can be mimicked by the exogenous administration of carbon monoxide (CO), a product of haem catabolism by HO-1 that restores placentation and fetal growth. In a clinical relevant model of IUGR, CO reduces the levels of free haem in circulation and prevents fetal death. We unravel a novel physiological role for HO-1/CO in sustaining pregnancy which aids in understanding the biology of pregnancy and reveals a promising therapeutic application in the treatment of pregnancy pathologies.     

PAS-Induced Potentiation of Cortical-Evoked Activity in the Dorsolateral Prefrontal Cortex

Neuroplasticity and long-term potentiation (LTP) in the dorsolateral prefrontal cortex (DLPFC) are considered important mechanisms in learning and memory, and their disruption may be related to the pathophysiology of several neuropsychiatric disorders. Paired associative stimulation (PAS) is a brain stimulation paradigm that produces enhanced activity in the human motor cortex that may be related to LTP. In a group of 15 healthy participants, we report on the potentiation of cortical-evoked activity in the human DLPFC using the combination of PAS and electroencephalography. In contrast, a PAS control condition did not result in potentiation in another group of nine healthy participants. We also demonstrate that PAS-induced potentiation of cortical-evoked activity is characterized by anatomical specificity that is largely confined to the site of stimulation. Finally, we show that PAS results in potentiation of θ- and γ-activity and θ-phase–γ-amplitude coupling. These neurophysiological indices may be related to working memory, an important function of the DLPFC. To our knowledge, this is the first report of potentiation of cortical-evoked activity in the DLPFC. As this potentiation may be related to LTP, our findings provide a model through which neuroplasticity in health and disease states in the frontal cortex can be studied.     

Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a prospective randomized study

Purpose

Eradication rates following standard triple therapy for Helicobacter pylori infection are declining. Recent studies, conducted in a number of countries, have shown that sequential therapy for H. pylori infection yields high cure rates.

Aim

To compare the efficacy and tolerability of a sequential regimen as a first-line treatment of H. pylori infection with a standard triple treatment regime in Morocco.

Methods

A total of 281 naive H. pylori-infected patients, confirmed by histological examination, were assigned randomly to one of two treatment groups: standard triple therapy [omeprazole (20 mg bid) + amoxicillin (1 g bid) + clarithromycin (500 mg bid) for 7 days] or sequential therapy [omeprazole (20 mg bid) + amoxicillin (1 g bid) for 5 days, followed by omeprazole (20 mg bid) + tinidazole (500 mg bid) + clarithromycin (500 mg bid) for an additional 5 days]. H. pylori eradication was checked 4–6 weeks after treatment initiation by using a ¹³C-urea breath test. Compliance and adverse events were assessed.

Results

The two groups did not differ significantly in gender, age, previous disease history, endoscopic and histological features and smoking. The intention-to-treat and per-protocol eradication rates were 65.9 and 71 % in the standard triple therapy group, and 82.8 and 89.9 % in the sequential therapy group, respectively. The eradication rate was significantly higher in the sequential therapy group than in the standard triple therapy group (p?<?0.001), There was no statistically significant difference in compliance (97.5  vs. 96.3 %) and incidence of side-effects (27.5 vs. 27.9 %) between the two groups.

Conclusions

Based on our results, we conclude that for eradication of H. pylori infection, the 10-day sequential therapy is more effective than the standard triple therapy and is equally tolerated. These results confirm those of other studies in other countries.     

Alpha-Lipoic Acid Improves Subclinical Left Ventricular Dysfunction in Asymptomatic Patients with Type 1 Diabetes

BACKGROUND: Oxidative stress plays an important role in the development of diabetic cardiomyopathy. Alpha-lipoic acid (ALA) is a powerful antioxidant that may have a protective role in diabetic cardiac dysfunction. AIM: We investigated the possible beneficial effect of alpha-lipoic acid on diabetic left ventricular (LV) dysfunction in children and adolescents with asymptomatic type 1 diabetes (T1D). SUBJECTS AND METHODS: Thirty T1D patients (aged 10-14) were randomized to receive insulin treatment (n = 15) or insulin plus alpha-lipoic acid 300 mg twice daily (n = 15) for four months. Age and sex matched healthy controls (n = 15) were also included. Patients were evaluated with conventional 2-dimensional echocardiographic examination (2D), pulsed tissue Doppler (PTD), and 2-dimensional longitudinal strain echocardiography (2DS) before and after therapy. Glutathione, malondialdhyde (MDA), nitric oxide (NO), tumor necrosis factor-alpha (TNF-alpha), Fas ligand (Fas-L), matrix metalloproteinase 2 (MMP-2), and troponin-I were determined and correlated to echocardiographic parameters. RESULTS: Diabetic patients had significantly lower levels of glutathione and significantly higher MDA, NO, TNF-alpha, Fas-L, MMP-2, and troponin-I levels than control subjects. The expression of transforming growth factor beta (TGF-beta) mRNA in peripheral blood mononuclear cells was also increased in diabetic patients. Significant correlations of mitral e''/a'' ratio and left ventricular global peak systolic strain with glutathione, MDA, NO, TNF-alpha, and Fas-L were observed in diabetic patients. Alpha-lipoic acid significantly increased glutathione level and significantly decreased MDA, NO, TNF-alpha, Fas-L, MMP-2, troponin-I levels, and TGF-beta gene expression. Moreover, alpha-lipoic acid significantly increased mitral e''/a'' ratio and left ventricular global peak systolic strain in diabetic patients. CONCLUSION: These findings suggest that alpha-lipoic acid may have a role in preventing the development of diabetic cardiomyopathy in type 1 diabetes.     

Impact of tigecycline versus imipenem–cilastatin on fibrinogen levels following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC): a randomized-controlled study

The aim of this prospective, randomized study was to compare the effects of tigecycline and imipenem-cilastatin on fibrinogen levels in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Patients were empirically randomized to receive tigecycline or imipenem–cilastatin. Fibrinogen levels were measured in both patient groups on days 1, 3, 5 and 8 of antibiotic therapy and 3 days after antibiotic therapy completion. Twenty patients received tigecycline and 22 patients received imipenem–cilastatin . Patients in the tigecycline group had lower mean fibrinogen levels compared to those in the imipenem–cilastatin group on day 3 (4.1 ± 1.2 vs. 5.9 ± 1.3 g/L; p < 0.001), day 5 (3.7 ± 1.2 vs. 6.5 ± 1.1 g/L; p < 0.001), day 8 (3.5 ± 1.3 vs. 5.8 ± 1.6 g/L; p < 0.001), and day 3 after antibiotic completion (4.1 ± 1.4 vs. 6.1 ± 1.6 g/L; p < 0.001). In conclusion, compared to imipenem–cilastatin, tigecycline was associated with a significant decrease in fibrinogen levels, following CRS and HIPEC.