Ahmet Turan Isik

Metformin in the treatment of patients with non‐alcoholic steatohepatitis

Background : Increased insulin resistance is the major pathogenic mechanism in the development of non‐alcoholic steatohepatitis.

Inflammation and frailty in the elderly: A systematic review and meta-analysis

The pathogenesis of frailty and the role of inflammation is poorly understood. We examined the evidence considering the relationship between inflammation and frailty through a systematic review and meta-analysis. A systematic literature search of papers providing data on inflammatory biomarkers and frailty was carried out in major electronic databases from inception until May 2016. From 1856 initial hits, 35 studies (32 cross-sectional studies n=3232 frail, n=11,483 pre-frail and n=8522 robust, and 563 pre-frail+robust; 3 longitudinal studies n=3402 participants without frailty at baseline) were meta-analyzed. Cross-sectional studies reported that compared to 6757 robust participants, both 1698 frail (SMD=1.00, 95%CI: 0.40-1.61) and 8568 pre-frail (SMD=0.33, 95%CI: 0.04-0.62) participants had significantly higher levels of C-reactive protein (CRP). Frailty (n=1057; SMD=1.12, 95%CI: 0.27-2.13) and pre-frailty (n=4467; SMD=0.56, 95%CI: 0.00-1.11) were associated with higher serum levels of interleukin-6 compared to people who were robust (n=2392). Frailty and pre-frailty were also significantly associated with elevated white blood cell and fibrinogen levels. In three longitudinal studies, higher serum CRP (OR=1.06, 95%CI: 0.78-1.44,) and IL-6 (OR=1.19, 95%CI: 0.87-1.62) were not associated with frailty. In conclusion, frailty and pre-frailty are associated with higher inflammatory parameters and in particular CRP and IL-6. Further longitudinal studies are needed.

ReviewInflammation and frailty in the elderly: A systematic review and meta-analysis

The pathogenesis of frailty and the role of inflammation is poorly understood. We examined the evidence considering the relationship between inflammation and frailty through a systematic review and meta-analysis. A systematic literature search of papers providing data on inflammatory biomarkers and frailty was carried out in major electronic databases from inception until May 2016. From 1856 initial hits, 35 studies (32 cross-sectional studies n=3232 frail, n=11,483 pre-frail and n=8522 robust, and 563 pre-frail+robust; 3 longitudinal studies n=3402 participants without frailty at baseline) were meta-analyzed. Cross-sectional studies reported that compared to 6757 robust participants, both 1698 frail (SMD=1.00, 95%CI: 0.40-1.61) and 8568 pre-frail (SMD=0.33, 95%CI: 0.04-0.62) participants had significantly higher levels of C-reactive protein (CRP). Frailty (n=1057; SMD=1.12, 95%CI: 0.27-2.13) and pre-frailty (n=4467; SMD=0.56, 95%CI: 0.00-1.11) were associated with higher serum levels of interleukin-6 compared to people who were robust (n=2392). Frailty and pre-frailty were also significantly associated with elevated white blood cell and fibrinogen levels. In three longitudinal studies, higher serum CRP (OR=1.06, 95%CI: 0.78-1.44,) and IL-6 (OR=1.19, 95%CI: 0.87-1.62) were not associated with frailty. In conclusion, frailty and pre-frailty are associated with higher inflammatory parameters and in particular CRP and IL-6. Further longitudinal studies are needed.

The effect of activated protein C on experimental acute necrotizing pancreatitis

IntroductionAcute pancreatitis is a local inflammatory process that leads to a systemic inflammatory response in the majority of cases. Bacterial contamination has been estimated to occur in 30–40% of patients with necrotizing pancreatitis. Development of pancreatic necrosis depends mainly on the degree of inflammation and on the microvascular circulation of the pancreatic tissue. Activated protein C (APC) is known to inhibit coagulation and inflammation, and to promote fibrinolysis in patients with severe sepsis. We investigated the effects of APC on histopathology, bacterial translocation, and systemic inflammation in experimental acute necrotizing pancreatitis.Materials and methodForty-five male Sprague-Dawley rats were studied. Rats were randomly allocated to three groups. Acute pancreatitis was induced in group II (positive control; n = 15) and group III (treatment; n = 15) rats by retrograde injection of taurocholate into the common biliopancreatic duct. Group I rats (sham; n = 15) received an injection of normal saline into the common biliopancreatic duct to mimic a pressure effect. Group III rats were treated with intravenous APC 6 hours after induction of pancreatitis. Pancreatic tissue and blood samples were obtained from all animals for histopathological examination and assessment of amylase, tumor necrosis factor-α, and IL-6 levels in serum. Bacterial translocation to pancreas and mesenteric lymph nodes was measured.ResultsAcute pancreatitis developed in all groups apart from group I (sham), as indicated by microscopic parenchymal necrosis, fat necrosis and abundant turbid peritoneal fluid.Histopathological pancreatitis scores in the APC-treated group were lower than in positive controls (10.31 ± 0.47 versus 14.00 ± 0.52; P < 0.001). Bacterial translocation to mesenteric lymph nodes and to pancreas in the APC-treated group was significantly decreased compared with controls (P < 0.02 and P < 0.007, respectively). Serum amylase, tumor necrosis factor--α, and IL-6 levels were also significantly decreased in comparison with positive controls (P < 0.001, P < 0.04 and P < 0.001, respectively).ConclusionAPC improved the severity of pancreatic tissue histology, superinfection rates and serum markers of inflammation during the course of acute necrotizing pancreatitis.

Rat liver fibrosis regresses better with pegylated interferon alpha2b and ursodeoxycholic acid treatments than spontaneous recovery.

Abstract: Background/aims: Fibrosis and cirrhosis are common complications of chronic liver diseases. An imbalance between fibrogenesis and fibrolysis results in scarring of the liver parenchyma. We aimed to investigate the possible antifibrotic effectiveness of a newly modified interferon molecule peginterferon α2b (PEG‐IFNα2b) which has better antiviral activity, and ursodeoxycholic acid (UDCA).

Effects of pioglitazone and retinoic acid in a rotenone model of Parkinson's disease.

Parkinsons disease (PD) is a late-onset, progressive and neurodegenerative disorder of unknown etiology. Besides the other therapeutic approaches, new drug options in pharmacotherapy of PD are important. The aim of the present study was to investigate the effects of pioglitazone and retinoic acid, antioxidant and neuroprotective agents, on rotenone-induced model of PD in rats. Adult male Wistar rats (260-373 g) were subjects. Rotenone (2.5mg/kg, sc) was injected to rats for 70 days. At the end of rotenone administration, rats were treated with pioglitazone (10mg/kg, ip) and retinoic acid (1mg/kg, ip) or vehicles for 15 days. Then, rats were tested for evaluation of Parkinson signs by measurement of locomotor activity. In addition, dopamine levels were detected in striatum, hippocampus and hypothalamus in individual groups of control, rotenone and pioglitazone or retinoic acid-treated rats. Rotenone significantly reduced locomotor activity of the rats. It also significantly reduced dopamine levels in striatum and hippocampus, but not hypothalamus. Pioglitazone and retinoic acid reversed in reduction of locomotor activity significantly. Pioglitazone, but not retinoic acid, significantly reversed the reduced striatal dopamine level. Both drugs were ineffective on reduced levels of dopamine in hippocampus. Our results suggest that pioglitazone and retinoic acid have some beneficial effects on rotenone-induced model of PD in rats. Pioglitazone seems to be more effective than retinoic acid. These agents may be helpful for preventing or controlling of some signs of PD.

Late onset Alzheimer's disease in older people

Dementia has become a common diagnosis in aging populations, and the numbers will increase in the forthcoming years. Alzheimer’s disease (AD) is the most common form of dementia in the elderly, accounting for 50%–56% of cases at autopsy and in clinical series. Nowadays, the number of people affected by AD is rapidly increasing, and more than 35 million people worldwide have AD, a condition characterized by deterioration of memory and other cognitive domains, and leading to death 3–9 years after diagnosis. The number of patients with AD, the most common cause of disability in the elderly, is set to rise dramatically. Therefore, it is important for clinicians to recognize early signs and symptoms of dementia and to note potentially modifiable risk factors and early disease markers.

Allopurinol in rat chronic pancreatitis: effects on pancreatic stellate cell activation.

Objectives: Activation of pancreatic stellate cells (PSCs) is a key event in pancreatic fibrosis. Xanthine oxidase-derived free radicals are involved in the mechanism of chronic pancreatitis (CP). We here searched the in vivo effects of allopurinol on PSC activation and its relation to tissue oxidative stress and histological findings in rat CP. Methods: Rat CP was induced with intraductal trinitrobenzene sulfonic acid in groups 1 (n = 16) and 2 (n = 10). Group 3 (n = 10) received intraductal saline. Four weeks after induction, group 1 received allopurinol (200 mg/kg, SC), and groups 2 and 3 received saline. After 4 weeks, oxidative stress parameters, histological evaluation, and immunostaining for α-smooth muscle actin (+) PSCs were performed in the pancreata. Results: Oxidative stress parameters improved significantly in group 1 compared with groups 2 and 3. Collagen deposition and lobular/sublobular atrophy were significantly lower in group 1 than in group 2. α-smooth muscle actin (+) PSCs counts in group 1 were significantly lower than in group 2, and were in correlation with the degree of fibrosis and atrophy. Conclusions: Allopurinol inhibits PSC activation in vivo. Pancreatic fibrosis can be prevented, at least in part, by antioxidant treatment through xanthine oxidase metabolism. Long-term use of allopurinol and its analogs may be considered in clinical trials with CP.

The effect of combination therapy of hyperbaric oxygen, meropenem, and selective nitric oxide synthase inhibitor in experimental acute pancreatitis.

Despite the new diagnostic and therapeutic advancements, acute pancreatitis has still high rate of morbidity and mortality. We aimed to evaluate the effects of hyperbaric oxygen (HBO) therapy alone or combined with S-methylisothiourea (SMT), and meropenem (MER) therapy in an experimental rat model of acute necrotizing pancreatitis. Rats were randomly divided into 8 groups, and acute pancreatitis was induced in all groups except group 1. Treatment protocols were saline for group 2, SMT for group 3, SMT + MER for group 4, SMT + HBO for group 5, HBO for group 6, HBO + MER for group 7, and MER for group 8. All surviving animals were killed 48 hours after the induction of pancreatitis, and specimens were collected. Oxidative stress parameters, histopathologic scores and amylase levels were better in treatment groups than in the positive control group (group 2). The most favorable results were obtained in HBO treatment groups, especially in HBO + MER group (group 7). Our results indicate that adding HBO therapy to the antibiotic therapy will decrease oxidative stress parameters, serum amylase levels, and histopathological score. We suggest that adding the HBO therapy as an adjunctive to the treatment protocol of acute necrotizing pancreatitis may yield improvement in the morbidity and mortality of the disease.

Which cholinesterase inhibitor is the safest for the heart in elderly patients with Alzheimer's disease?

Objective: Cholinesterase inhibitors (ChEIs) are widely used for the treatment of Alzheimer’s disease (AD); however, their cholinergic side effects on the cardiovascular system are still unclear. In this study, we aimed to examine the side effects caused by donepezil, rivastigmine, and galantamine on cardiac rhythm and postural blood pressure changes in elderly patients with AD. Methods: Of 204 consecutive elderly patients who were newly diagnosed with AD, 162 were enrolled and underwent comprehensive geriatric assessments. The electrocardiographs (ECGs) and blood pressures were recorded at the baseline and 4 weeks after the dose of 10 mg/d of donepezil, 10 cm2/d of rivastigmine, and 24 mg/d of galantamine. Results: There were no changes relative to the baseline in any of the ECG parameters or arterial blood pressure with any of the administered ChEIs. Conclusion: It was demonstrated that none of the 3 ChEIs were associated with increased negative chronotropic, arrhythmogenic, and hypotensive effects for the elderly patients with AD.