The Akt inhibitor,triciribine, ameliorates chronic hypoxia-induced vascular pruning and TGFβ-induced pulmonary fibrosis

Background and Purpose

Interstitial lung disease accounts for a group of chronic and progressive disorders associated with severe pulmonary vascular remodelling, peripheral vascular rarefaction and fibrosis, thus limiting lung function. We have previously shown that Akt is necessary for myofibroblast differentiation, a critical event in organ fibrosis. However, the contributory role of the Akt-mTOR pathway in interstitial lung disease and the therapeutic benefits of targeting Akt and mTOR remain unclear.

Experimental Approach

We investigated the role of the Akt-mTOR pathway and its downstream molecular mechanisms in chronic hypoxia- and TGFβ-induced pulmonary vascular pruning and fibrosis in mice. We also determined the therapeutic benefits of the Akt inhibitor triciribine and the mTOR inhibitor rapamycin for the treatment of pulmonary fibrosis in mice.

Key Results

Akt1^−/− mice were protected from chronic hypoxia-induced peripheral vascular pruning. In contrast, hyperactivation of Akt1 induced focal fibrosis similar to TGFβ-induced fibrosis. Pharmacological inhibition of Akt, but not the Akt substrate mTOR, inhibited hypoxia- and TGFβ-induced pulmonary vascular rarefaction and fibrosis. Mechanistically, we found that Akt1 modulates pulmonary remodelling via regulation of thrombospondin1 (TSP1) expression. Hypoxic Akt1^−/− mice lungs expressed less TSP1. Moreover, TSP1^−/− mice were resistant to adMyrAkt1-induced pulmonary fibrosis.

Conclusions and Implications

Our study identified Akt1 as a novel target for the treatment of interstitial lung disease and provides preclinical data on the potential benefits of the Akt inhibitor triciribine for the treatment of interstitial lung disease.     

Anti-arrhythmia effect of prolecophen in patients with extrasystole in comparison with other anti-arrhythmia drugs

Oral prolecohen (LEK, Yugoslavia) was given in a single dose of 300 mg to 15 patients with extrasystole of various genesis. The drug produced an antiarrhythmic effect in 50% of patients with ventricular extrasystole, but in those with supraventricular extrasystole. Prolecophenum showed a good tolerance. In 20% of the patients the adverse reactions appeared as mild headache, dizziness, dry mouth, malaise in the epigastric region. There is also evidence for efficacy of other antiarrhythmic agents used in this group of patients.     

Imaging techniques for muscle injury in sports medicine and clinical relevance

Magnetic resonance imaging (MRI) and ultrasound are the imaging modalities of choice to assess muscle injuries in athletes. Most authors consider MRI as the reference standard for evaluation of muscle injuries, since it superiorly depicts the extent of injuries independently of its temporal evolution, and due to the fact that MRI seems to be more sensitive for the detection of minimal injuries. Furthermore, MRI may potentially allow sports medicine physicians to more accurately estimate recovery times of athletes sustaining muscle injuries in the lower limbs, as well as the risk of re-injury. However, based on data available, the specific utility of imaging (including MRI) regarding its prognostic value remains limited and controversial. Although high-quality imaging is systematically performed in professional athletes and data extracted from it may potentially help to plan and guide management of muscle injuries, clinical (and functional) assessment is still the most valuable tool to guide return to competition decisions.     

Laparoscopy assisted transjejunal endoscopic retrograde cholangiography for treatment of intrahepatic duct stones in a post Roux-en-Y patient

We report a case of a 17-year-old female patient, who was operated on for choledocal cyst with Roux-en Y hepatojejunostomy. She was admitted to hospital with recurrent attacks of acute ascending cholangitis due to left intrahepatic duct stones. After a failed attempt at conventional endoscopic retrograde cholangiopancreatography through the anatomical route, she was treated successfully with laparoscopy assisted transjejunal endoscopic retrograde cholangiography.Endoscopic access to the biliary system can be difficult in patients with surgically altered anatomy of the upper gastrointestinal tract (GIT), such as Roux-en-Y reconstruction, because of the changed anatomy. However, endoscopic retrograde cholangiopancreatography (ERCP) is challenging in cases such as our patient;1,2 this is due to the distance needed to be traversed and looping. Our objective in presenting this particular case is to describe and highlight a laparoscopy assisted transjejunal ERCP to permit successful treatment and removal of intrahepatic duct stones in a post Roux-en-Y patient, and to minimize surgical inetervention to reduce unnecessary risks to the patient.     

Long-term compliance with continuous positive airway pressure in Saudi patients with obstructive sleep apnea: A prospective cohort study

Objectives:

To evaluate continuous positive airway pressure (CPAP) compliance and define predictors of CPAP compliance among Saudi patients with obstructive sleep apnea (OSA) after applying an educational program.

Methods:

This prospective cohort study included consecutive patients diagnosed to have OSA based on polysomnography between January 2012 and January 2014 in King Saud University, Riyadh, Kingdom of Saudi Arabia. All patients had educational sessions on OSA and CPAP therapy before sleep study, and formal hands-on training on CPAP machines on day one, day 7, and day 14 after diagnosis. The follow-up in the clinic was carried out at one, 4, and 10 months after initiating CPAP therapy. Continuous positive airway pressure compliance was assessed objectively. Logistic regression model was used to assess the predictors of CPAP adherence.

Results:

The study comprised 156 patients with a mean age of 51.9±12.1 years, body mass index of 38.4±10.6 kg/m², and apnea hypopnea index of 63.7±39.3 events/hour. All patients were using CPAP at month one, 89.7% at month 4, and 83% at month 10. The persistence of CPAP-related side effects and comorbid bronchial asthma remained as independent predictors of CPAP compliance at the end of the study.

Conclusion:

With intensive education, support, and close monitoring, more than 80% of Saudi patients with OSA continued to use CPAP after 10 months of initiating CPAP therapy.Continuous positive airway pressure (CPAP) is a standard, safe, and efficacious treatment for obstructive sleep apnea (OSA), a common disorder with established harm to quality of life and adverse consequences for cardiovascular health.1 Obstructive sleep apnea is characterized by recurrent partial (hypopnea) or complete (apnea) upper airway obstruction during sleep. These recurrent respiratory events usually cause intermittent hypoxemia and sleep fragmentation.2 Recent data demonstrated that the estimated prevalence of moderate to severe OSA ranges from 10-17% in middle-aged and elderly men.3 In Saudi Arabia, 3 out of 10 middle-aged Saudi men and 4 out of 10 middle-aged Saudi women are at high risk of having OSA.4,5 The mainstay medical treatment for OSA is CPAP therapy.6 Among various available therapeutic modalities for OSA, CPAP remains the most effective treatment.6 Continuous positive airway pressure is a machine that applies positive airway pressure to the upper air passages via a mask fitted on the mouth or nose to keep the throat open.6 Previous studies in Western countries showed that OSA patients on CPAP therapy use their machines on average from 4.5 to 5.5 hours per night with compliance rates ranging from 30-85%.7,8 Several studies have been conducted to define factors that influence, or predict CPAP use and adherence, and reported conflicting results.6 Moreover, several studies reported that race might influence CPAP adherence. For example, available data suggest lower CPAP adherence among African Americans than Caucasians.9 An earlier study that assessed CPAP compliance subjectively (self-reports) among Saudi patients with OSA after 3 months of initiation of CPAP therapy revealed an overall compliance rate of 39%.10 However, self-reports have been shown to overestimate CPAP use by approximately one hour/night when compared with objectively measured CPAP use.11 In general, there are very few data on objectively assessed long-term CPAP compliance in the literature. Moreover, there is a lack of previous study objectively addressing the rate of CPAP compliance, the predictors of good compliance, and the side effects of CPAP treatment in Saudi OSA patients. Therefore, we established in our center an educational program for patients with OSA and easily accessible medical support, and close follow-up of CPAP compliance. This study was conducted to evaluate CPAP compliance and to define predictors of CPAP compliance among Saudi patients with OSA after applying the new educational program.