Dexamethasone Addition Impairs the Therapeutic Effects of Nimodipine for Subarachnoid Hemorrhage: An Experimental Animal Study.

AIM: To evaluate the effects of the combination of nimodipine and dexamethasone in subarachnoid hemorrhage (SAH). MATERIAL AND METHODS: In this study, 35 female adult Wistar Albino rats were randomly assigned to four groups: Sham (n=8), SAH with no treatment (n=9), SAH with nimodipine (n=9, oral gavage, 12 mg/kg, BID) treatment, and SAH with combined therapy with nimodipine and dexamethasone (n=9, intraperitoneally, 1mg/kg, BID). The "cisterna magna double injection of autologous blood" model was used. The animals were euthanized 5 days after the first injection. RESULTS: Of the total, five rats died before euthanasia. The SAH+Nontreatment group showed the worst score in neurological examinations, and the most severe histopathological findings were noted in terms of vasospasm. The SAH+Nimodipine group showed the best neurological score and the closest histopathological results to those of the Sham group, whereas adding dexamethasone to nimodipine treatment (the SAH+Nimodipine+Dexamethasone group) worsened the neurological and histopathological outcomes. CONCLUSION: We thus concluded that the therapeutic effects of nimodipine were impaired when combined with dexamethasone. We thus hypothesized that dexamethasone possibly induces the CYP3A4-enzyme that metabolizes nimodipine. However, it should be noted that our results are based on laboratory findings obtained on a small sample, therefore further studies with drug-drug interaction on a larger sample size through CYP3A4-enzyme and clinical confirmation are warranted.

The prognostic role of epidermal growth factor receptor mutation in completely resected ampullary adenocarcinoma.

The aim of this study is to make a differential diagnosis and prognosis of the ampullary adenocarcinoma subtypes. We also investigated the role of prognostic markers PD-1 and PD-L1, and epidermal growth factor receptor (EGFR). Local or locally advanced stage ampullary adenocarcinoma patients who had undergone pancreaticoduodenectomy at the time of diagnosis were included. MUC1, MUC2, MUC5AC, CDX2, CK7, CK20, PD-1, and PDL-1 were analysed immunohistochemically, and EGFR was analysed by real-time polymerase chain reaction. According to histopathological and immunohistochemical evaluation, we found 27 patients as pancreatobiliary type and 56 patients as intestinal type adenocarcinoma. The median survival of patients with intestinal and pancreatobiliary type adenocarcinoma was 23 months and 76 months ( p = 0.201), respectively. When the survival of PD1-positive ( n = 23) and PD-L1-positive ( n = 18) patients were compared with the patients with negative staining ( n = 60, n = 65), no significant difference was found. Epidermal growth factor receptor mutation was detected in a total of 6 patients, and 5 of these 6 mutations were shown in intestinal type tumours and one in a pancreatobiliary type tumour. A significant difference was determined in terms of overall survival for the patients with EGFR mutations compared to those without ( p = 0.008). In conclusion, we could reveal the prognostic significance of EGFR mutation, which is also a target molecule.

A Comparison of Cerebrospinal Fluid Beta-Amyloid and Tau in Idiopathic Normal Pressure Hydrocephalus and Neurodegenerative Dementias.

Purpose: Idiopathic normal pressure hydrocephalus (iNPH) is the leading reversible cause of cognitive impairment and gait disturbance that has similar clinical manifestations and accompanies to major neurodegenerative disorders in older adults. We aimed to investigate whether cerebrospinal fluid (CSF) biomarker for Alzheimer's disease (AD) may be useful in the differential diagnosis of iNPH. Patients and Methods: Amyloid-beta (Aß) 42 and 40, total tau (t-tau), phosphorylated tau (p-tau) were measured via ELISA in 192 consecutive CSF samples of patients with iNPH (n=80), AD (n=48), frontotemporal dementia (FTD) (n=34), Lewy body diseases (LBDs) (n=30) consisting of Parkinson's disease dementia and dementia with Lewy bodies. Results: The mean age of the study population was 75.6±7.7 years, and 54.2% were female. CSF Aß42 levels were significantly higher, and p-tau and t-tau levels were lower in iNPH patients than in those with AD and LBDs patients. Additionally, iNPH patients had significantly higher levels of t-tau than those with FTD. Age and sex-adjusted multi-nominal regression analysis revealed that the odds of having AD relative to iNPH decreased by 37% when the Aß42 level increased by one standard deviation (SD), and the odds of having LBDs relative to iNPH decreased by 47%. The odds of having LBDs relative to iNPH increased 76% when the p-tau level increased 1SD. It is 2.5 times more likely for a patient to have LBD relative to NPH and 2.1 times more likely to have AD relative to iNPH when the t-tau value increased 1SD. Conclusion: Our results suggest that levels of CSF Aß42, p-tau, and t-tau, in particularly decreased t-tau, are of potential value in differentiating iNPH from LBDs and also confirm previous studies reporting t-tau level is lower and Aß42 level is higher in iNPH than in AD.

The applause sign in elderly patients with idiopathic normal pressure hydrocephalus.

Applause sign (AS) was shown to be an indicator of frontal subcortical dysfunction in many neurodegenerative diseases. Idiopathic normal pressure hydrocephalus (INPH) is one of those in which frontosubcortical disconnection can be displayed. We aimed to examine the presence of AS in the elderly patients with INPH and its possible diagnostic role in the frontal dysfunction commonly seen in the disease. Sixty-six patients diagnosed with probable INPH, 32 with behavioral variant of frontotemporal dementia (bvFTD) and 325 healthy elderly subjects were included in this cross-sectional and retrospective study. AS was evaluated with the clapping test. Patients with INPH were further assessed with frontal assessment battery (FAB), Stroop test, verbal fluency test and clock drawing test (CDT). The concentration of total amyloid-ß 42 (Aß42), Aß40, total (t) tau and phosphorylated (p)-tau proteins were also measured in the cerebrospinal fluid (CSF). AS was observed in all groups (40% in bvFTD, 28.8% in INPH, 1.2% in controls, respectively). It was significantly more frequent in patients with bvFTD and INPH as compared to the controls (p < 0.001, for each). The frequency was similar in the patients with bvFTD and INPH (p = 0.802). Significant differences were found between the AS(+) and (-) INPH patients with regards to FAB, Stroop test-errors and verbal fluency test, except for the CSF proteins. AS can be used as a simple, useful and rapid clinical test that investigates executive dysfunction in elderly patients with INPH in both inpatient and outpatient settings.

The efficacy of systemic and intravitreal infliximab treatments in an endotoxin-induced uveitis model.

Purpose: To compare the efficacy of systemic and intravitreal infliximab treatments in an experimental endotoxin-induced uveitis (EIU) model. Methods: Twenty-eight white New Zealand rabbits were equally divided into 4 groups. Group 1 received an intravitreal injection of 0.1 cc saline, group 2 received an intravitreal injection of 2 µg/0.1 cc lipopolysaccharide (LPS), group 3 received an intravitreal injection of 2 µg/0.1 cc LPS and 2 mg/0.1 cc infliximab, and group 4 received intravitreal injection of 2 µg/0.1 cc LPS and intravenous injection of 5 mg/kg infliximab. Clinical, biochemical (aqueous and vitreous humour protein levels and TNF-α concentrations), and histopathological evaluations were performed. Results: The clinical examination score was lower in group 4 than in group 2 (p = 0.006); but there was no significant difference between groups 2 and 3 (Bonferroni correction, p = 0.016). No statistically significant difference was found among groups 2, 3, and 4 for aqueous humour protein levels (p > 0.05). Significantly higher aqueous humour concentrations of TNF-α was measured in group 3 comparing to both group 1 and 4 (p = 0.003 and p = 0.002, respectively). No significant difference was found in vitreous protein levels or TNF-α concentrations among all study groups (Bonferroni correction, p = 0.026 and p = 0.101, respectively). Histopathological evaluation of the uveal tissue and anterior chamber reaction revealed the highest inflammation in group 3 (p < 0.001). In group 4, histopathological evaluation of uveal tissue was lower than in groups 2 and 3 (p < 0.001 and p = 0.001, respectively); whereas there was no difference in anterior chamber inflammation between groups 2 and 4 (p = 1.00). Conclusion: Intravitreal 2 mg/0.1 cc infliximab injection exacerbated inflammation in an EIU model; whereas systemic infliximab treatment at a dose of 5 mg/kg suppressed inflammation effectively and rapidly.

Which Mechanism is Effective on the Hyperamylasaemia After Coronary Artery Bypass Surgery?

BACKGROUND AND AIM: Acute pancreatitis is one of the less frequently diagnosed lethal abdominal complications of cardiac surgery. The incidence of early postoperative period hyperamylasaemia was reported to be 30-70% of patients who underwent coronary artery bypass grafting (CABG) with cardiopulmonary bypass (CPB). The mechanism of pancreatic enzyme elevation after cardiac surgery is not clear. Our aim was to determine the relationship between ischaemia associated temporary renal dysfunction and elevation of pancreatic enzymes after CABG. METHODS: Forty-one consecutive patients undergoing CABG under CPB were prospectively studied to determine serum total amylase, phospholipase A2, macroamylase, Cystatin C and urine NAG levels. RESULTS: Hyperamylasaemia was observed in 88% of the cases, with a distribution of 6% at the beginning of cardioplegic arrest, 5% at the 20th minute after cardioplegic arrest, 7% at the 40th minute after cardioplegic arrest, 14% when the heart was re-started, 26% at the 6th hour of intensive care and 30% at the 24th hour of intensive care. All of these patients had asymptomatic isolated hyperamylasaemia, and none of them presented with clinical pancreatitis. As indicators of renal damage; Cystatin C and NAG levels were higher compared to baseline values. CONCLUSION: Amylase began to rise during initial extracorporeal circulation and reached a maximum level postoperatively at 6 and 24hours. Decreased amylase excretion is the main reason for post CABG hyperamylasaemia.

Protective effects of acetyl-L-carnitine on cisplatin cytotoxicity and oxidative stress in neuroblastoma.

The most widely used platinum-derived drug is cisplatin in neuroblastoma (NB) chemotherapy, which is severely neurotoxic. Acetyl-L-Carnitine (ALC) is a natural occurring compound with a neuroprotective activity in several experimental paradigms. The aim of this study was to determine the effects of ALC on cisplatin induced cytotoxicity and oxidative stress in NB cells. SH-SY5Y (N-Myc negative) and KELLY (N-Myc positive) human NB cell lines were used. Cisplatin induced apoptosis was assessed by using a Cell Death Detection ELISA(PLUS) kit. Lipid peroxidation levels were determined by HPLC analysis. Glutathione levels were determined spectrophotometrically. ALC was used prophylactic or after cisplatin application. The level of cisplatin doses were determined in both type of NB cells at which 50% cell death occurred along with synchronized apoptosis induced. Prophylactic 10 and 50 micromol of ALC concentrations were decreased cisplatin induced lipid peroxidation compared to controls that normally exhibited apoptosis especially in SH-SY5Y cells. Cisplatin caused oxidative stress through decreasing glutathione levels in both cell types. ALC were effectively inhibited the increase in cisplatin induced oxidized glutathione and lipid peroxidation formation in NB cells. We suggested that prophylactic ALC would be a useful agent for cisplatin induced toxicity in NB cells.

Effects of oral L-arginine supplementation on blood pressure and asymmetric dimethylarginine in stress-induced preeclamptic rats.

This study was carried out to elucidate the role of asymmetric dimethylarginine (ADMA) and nitric oxide (NO) in preeclampsia development, and to investigate the effect of L-arginine supplementation in rats. Preeclampsia was induced in pregnant rats using a stress model. L-arginine was administered orally and ADMA, urinary nitrate, and protein levels were measured on the 20th day of pregnancy. Compared with the group of rats that are normally pregnant, the levels of blood pressure (BP), protein excretion, and ADMA were significantly increased in preeclampsia which returned to normal levels following the supplementation of L-arginine. Both group of rats had similar urine nitrate levels. Arginine-ADMA-NO pathway is affected in preeclampsia. L-arginine supplementation decreased hypertension (HT), proteinuria, and ADMA levels indicating that taking L-arginine may be beneficial in preeclampsia treatment.