Improved antifibrotic effect of a combination of verapamil and silymarin in rat-induced liver fibrosis

Background and study aimsLiver fibrosis progresses to cirrhosis in several settings, for example, severe acute alcoholic hepatitis, and hepatitis C virus (HCV) reinfection after liver transplantation. Cirrhosis produces hepatocellular dysfunction, which is also a risk factor for hepatocellular carcinoma.We studied verapamil as a prophylactic, therapeutic antifibrotic drug alone and in combination with silymarin in experimental rat’s liver-induced fibrosis.Material and methodsLiver fibrosis was induced by intra-peritoneal injection of rats with pig serum 0.5 ml twice weekly for 6 weeks, which resulted in score three fibrosis. Prophylactic verapamil alone and silymarin alone and a combination of both were administered at the same time of induction of liver fibrosis and continued for the duration of induction. Therapeutic verapamil was started on the last day of fibrosis induction and continued for 4 weeks. The extent of liver fibrosis was evaluated using Ishak’s fibrosis score. Serum alanine aminotransferase (ALT) was measured for follow-up.ResultsCompared to fibrotic model rats, prophylactic verapamil, silymarin and combined verapamil plus silymarin significantly resulted in lower serum ALT levels. Prophylactic use of verapamil and silymarin each alone revealed score 2 fibrosis with positive α-SMA immunostaining; while prophylactic treatment with combined verapamil plus silymarin revealed no fibrosis supported by negative α-SMA immunostaining. Verapamil treated fibrotic rat’s liver revealed significant regression in liver fibrosis scores with positive α-SMA immunostaining.ConclusionsVerapamil alone has a more significant prophylactic than therapeutic antifibrotic effect against induced liver fibrosis; it was more significant than silymarin. The combination of verapamil and silymarin, showed the best protection through their synergistic antifibrotic effect.     

Increased PLA2 activity in the hippocampus of patients with temporal lobe epilepsy and psychosis

Objective

The aim of this work was to investigate whether increased activity of the enzyme phospholipase A₂ (PLA₂) in the brain, as frequently reported in schizophrenia, is also related to psychosis in epilepsy. Our working hypothesis was based on the increased prevalence of schizophrenia-like psychosis in patients with temporal lobe epilepsy (TLE) secondary to mesial temporal sclerosis (MTS), as compared to patients with other forms of epilepsy.

Methods

We determined PLA₂ activity in hippocampal tissue from 7 patients with TLE-MTS and psychosis, as compared to 9 TLE-MTS patients without psychosis. Hippocampal tissue was obtained from patients who underwent an anterior temporal lobectomy due to therapy-resistant epilepsy.

Results

We found that patients with TLE-MTS and psychosis had a significantly increased calcium-independent PLA₂ activity as compared to patients without psychosis (p = 0.016).

Conclusion

Our finding suggest that an increment in brain PLA₂ activity is not specific for schizophrenia, but rather may be associated to the manifestation of schizophrenia-like psychotic symptoms in general.     

Regenerative medicine as applied to solid organ transplantation: current status and future challenges

In the last two decades, regenerative medicine has shown the potential for “bench‐to‐bedside” translational research in specific clinical settings. Progress made in cell and stem cell biology, material sciences and tissue engineering enabled researchers to develop cutting‐edge technology which has lead to the creation of nonmodular tissue constructs such as skin, bladders, vessels and upper airways. In all cases, autologous cells were seeded on either artificial or natural supporting scaffolds. However, such constructs were implanted without the reconstruction of the vascular supply, and the nutrients and oxygen were supplied by diffusion from adjacent tissues. Engineering of modular organs (namely, organs organized in functioning units referred to as modules and requiring the reconstruction of the vascular supply) is more complex and challenging. Models of functioning hearts and livers have been engineered using “natural tissue” scaffolds and efforts are underway to produce kidneys, pancreata and small intestine. Creation of custom‐made bioengineered organs, where the cellular component is exquisitely autologous and have an internal vascular network, will theoretically overcome the two major hurdles in transplantation, namely the shortage of organs and the toxicity deriving from lifelong immunosuppression. This review describes recent advances in the engineering of several key tissues and organs.     

Intragastric balloon positioning and removal: sedation or general anesthesia?

Background  

Different anesthesiological techniques are currently used for intragastric balloon positioning and removal. The aim of this study is to compare different anesthesiological approaches for balloon positioning and removal in a large multicentric patient population.     

Gallstone disease in the elderly: are older patients managed differently?

Background  

This study aimed to describe the differences in the management of symptomatic gallstone disease within different elderly groups and to evaluate the association between older age and surgical treatment.     

Prediction of failure in vancomycin-treated methicillin-resistant Staphylococcus aureus bloodstream infection: a clinically useful risk stratification tool

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of bloodstream infection (BSI) and is often associated with invasive infections and high rates of mortality. Vancomycin has remained the mainstay of therapy for serious Gram-positive infections, particularly MRSA BSI; however, therapeutic failures with vancomycin have been increasingly reported. We conducted a comprehensive evaluation of the factors (patient, strain, infection, and treatment) involved in the etiology and management of MRSA BSI to create a risk stratification tool for clinicians. This study included consecutive patients with MRSA BSI treated with vancomycin over 2 years in an inner-city hospital in Detroit, MI. Classification and regression tree analysis (CART) was used to develop a risk prediction model that characterized vancomycin-treated patients at high risk of clinical failure. Of all factors, the Acute Physiology and Chronic Health Evaluation II (APACHE-II) score, with a cutoff point of 14, was found to be the strongest predictor of failure and was used to split the population into two groups. Forty-seven percent of the population had an APACHE-II score < 14, a value that was associated with low rates of clinical failure (11%) and mortality (4%). Fifty-four percent of the population had an APACHE-II score ≥ 14, which was associated with high rates of clinical failure (35%) and mortality (23%). The risk stratification model identified the interplay of three other predictors of failure, including the vancomycin MIC as determined by Vitek 2 analysis, the risk level of the source of BSI, and the USA300 strain type. This model can be a useful tool for clinicians to predict the likelihood of success or failure in vancomycin-treated patients with MRSA bloodstream infection.