Artemisia absinthium improves spatial performance and neuronal injury induced by amyloid- beta in the CA1 hippocampal area of male Wistar rats.

Alzheimer's disease is a neurodegenerative disorder. It is characterized by the presence of two aberrant structures in the brain, those are, amyloid plaques and neurofibrillary tangles, along with neuronal death. Amyloid-beta further exacerbates the metabolic decline and results in cognitive impairments. Because of the favorable antioxidant and anti-inflammatory activities of Artemisia absinthium (wormwood), this study aimed to evaluate the effects of hydroalcoholic extract of this plant on spatial memory performance, neuronal injury, and apoptosis induced by amyloid-beta. Forty-eight male Wistar rats (220-250 g) were divided into the following groups: 1) control; 2) sham (solvent; ICV); 3) amyloid-beta 1-40 (ICV); and 4) amyloid-beta plus A. absinthium (10, 50, and 100 mg/kg/day; gavage). Congo red and TUNEL staining were performed to investigate the neuronal injury. Also, the Morris water maze (MWM) test was used to evaluate the spatial memory of the experimental groups. The results showed that spatial memory for finding the hidden platform in the MWM task decreased significantly in the amyloid-beta group, compared to the control and sham groups. In contrast, treatment with A. absinthium improved spatial memory dose-dependently and reduced tissue degeneration, amyloid plaques, and apoptosis. It seems that the hydroalcoholic extract of A. absinthium, due to its antioxidant and anti-inflammatory activities, can effectively reverse spatial memory deficits and reduce amyloid-beta plaques.

Shrinking microbubbles with microfluidics: mathematical modelling to control microbubble sizes.

Microbubbles have applications in industry and life-sciences. In medicine, small encapsulated bubbles (<10 µm) are desirable because of their utility in drug/oxygen delivery, sonoporation, and ultrasound diagnostics. While there are various techniques for generating microbubbles, microfluidic methods are distinguished due to their precise control and ease-of-fabrication. Nevertheless, sub-10 µm diameter bubble generation using microfluidics remains challenging, and typically requires expensive equipment and cumbersome setups. Recently, our group reported a microfluidic platform that shrinks microbubbles to sub-10 µm diameters. The microfluidic platform utilizes a simple microbubble-generating flow-focusing geometry, integrated with a vacuum shrinkage system, to achieve microbubble sizes that are desirable in medicine, and pave the way to eventual clinical uptake of microfluidically generated microbubbles. A theoretical framework is now needed to relate the size of the microbubbles produced and the system's input parameters. In this manuscript, we characterize microbubbles made with various lipid concentrations flowing in solutions that have different interfacial tensions, and monitor the changes in bubble size along the microfluidic channel under various vacuum pressures. We use the physics governing the shrinkage mechanism to develop a mathematical model that predicts the resulting bubble sizes and elucidates the dominant parameters controlling bubble sizes. The model shows a good agreement with the experimental data, predicting the resulting microbubble sizes under different experimental input conditions. We anticipate that the model will find utility in enabling users of the microfluidic platform to engineer bubbles of specific sizes.

Subjective satisfaction and quality of life in patients prior to listing for liver transplantation.

OBJECTIVES: Differences in health-related quality of life (HR-QoL) perception between alcohol abusing and non-substance-dependent subjects with liver cirrhosis could depend on differences in personality profile and influence management of patients awaiting liver transplant. METHODS: We compared the perceptions of disease state in 78 male patients of similar disease severity divided into 2 groups based on etiology of cirrhosis: 47% had alcoholic cirrhosis, and 53% had hepatitis C virus(HCV)-related cirrhosis without alcohol abuse. Patients' perception of disease state was determined using the SAT-P questionnaire (a self-administered questionnaire that provides a global assessment of perceived HR-QoL and subjective well-being). The assessment yields 2 scales: an analytic scale based on 32 variables and a synthetic scale based on 5 factors. RESULTS: In patients with alcohol-related disease, ''psychological function'' was found to be more impaired,while ''sleep, diet, and free time'' was less impaired compared with subjects with HCV-related cirrhosis, suggesting dysfunction related to substance abuse with personality disturbance. CONCLUSIONS: The perception of disease state is different in alcohol-abusing patients with cirrhosis compared with those with cirrhosis unrelated to alcohol.

Nutritional intake, depressive symptoms and vitamin D status in hypertensive patients in the north of Iran: A case-control study.

OBJECTIVE: We investigated vitamin D status, body size, nutritional intake and depression status in hypertensive patients in the north of Iran that have special dietary habit and lifestyle according to their culture and geographical situation. MATERIALS AND METHODS: This study was conducted on 127 patients with newly recognized hypertension and the 120 normal participants, in the north of Iran. Anthropometric data was measured and demographic characteristics, dietary intake, depression and medical status were collected by valid questionnaires. Blood samples were measured for 25-hydroxyvitamin D. RESULTS: Hypertensive patients had significantly lower serum 25-hydroxyvitamin D than control group (16±8.7ng/mL vs. 19.8±8.4ng/mL; P=0.04). In adjusted model, serum 25-hydroxyvitamin D of less than 30ng/mL was associated with an almost 4-fold odds of hypertension. The odds of hypertension in depressed patients was 1.2 times higher than in those without depression (p=0.002). After adjusted logistic regression analysis for energy intake, significant association was observed between hypertension and some dietary nutrients, including cholesterol, fiber and vitamin D intake. There was no significant association between hypertension and body weight, waist circumference as well as BMI. CONCLUSION: The vitamin D status was lower in the most individuals and it causes a considerable increase in the risk of hypertension. Undesirable intake of some nutrients and depression also increase the risk of developing hypertension. Health training about suitable dietary habits, easier access to vitamin D supplementation and screening for depression in patients with hypertension are cost-effective tools to improve outcomes in Iran.

A novel alternating current multiple array electrothermal micropump for lab-on-a-chip applications.

The AC electrothermal technique is very promising for biofluid micropumping, due to its ability to pump high conductivity fluids. However, compared to electroosmotic micropumps, a lack of high fluid flow is a disadvantage. In this paper, a novel AC multiple array electrothermal (MAET) micropump, utilizing multiple microelectrode arrays placed on the side-walls of the fluidic channel of the micropump, is introduced. Asymmetric coplanar microelectrodes are placed on all sides of the microfluidic channel, and are actuated in different phases: one, two opposing, two adjacent, three, or all sides at the same time. Micropumps with different combinations of side electrodes and cross sections are numerically investigated in this paper. The effect of the governing parameters with respect to thermal, fluidic, and electrical properties are studied and discussed. To verify the simulations, the AC MAET concept was then fabricated and experimentally tested. The resulted fluid flow achieved by the experiments showed good agreement with the corresponding simulations. The number of side electrode arrays and the actuation patterns were also found to greatly influence the micropump performance. This study shows that the new multiple array electrothermal micropump design can be used in a wide range of applications such as drug delivery and lab-on-a-chip, where high flow rate and high precision micropumping devices for high conductivity fluids are needed.

Prenatal maternal immune activation increases anxiety- and depressive-like behaviors in offspring with experimental autoimmune encephalomyelitis.

Multiple sclerosis (MS) is thought to result from a combination of genetics and environmental factors. Several lines of evidence indicate that significant prevalence of anxiety and depression-related disorders in MS patients can influence the progression of the disease. Although we and others have already reported the consequences of prenatal maternal immune activation on anxiety and depression, less is known about the interplay between maternal inflammation, MS and gender. We here investigated the effects of maternal immune activation with Poly I:C during mid-gestation on the progression of clinical symptoms of experimental autoimmune encephalomyelitis (EAE; a mouse model of MS), and then anxiety- and depressive-like behaviors in non-EAE and EAE-induced offspring were evaluated. Stress-induced corticosterone and tumor necrosis factor-alpha (TNF-α) levels in EAE-induced offspring were also measured. Maternal immune activation increased anxiety and depression in male offspring, but not in females. This immune challenge also resulted in an earlier onset of the EAE clinical signs in male offspring and enhanced the severity of the disease in both male and female offspring. Interestingly, the severity of the disease was associated with increased anxiety/depressive-like behaviors and elevated corticosterone or TNF-α levels in both sexes. Overall, these data suggest that maternal immune activation with Poly I:C during mid-pregnancy increases anxiety- and depressive-like behaviors, and the clinical symptoms of EAE in a sex-dependent manner in non-EAE or EAE-induced offspring. Finally, the progression of EAE in offspring seems to be linked to maternal immune activation-induced dysregulation in neuro-immune-endocrine system.

Azalanstat (RS-21607), a lanosterol 14 alpha-demethylase inhibitor with cholesterol-lowering activity.

Agents that inhibit hepatic cholesterol biosynthesis reduce circulating cholesterol levels in experimental animals and humans, and may be of pharmacological importance in the prevention of atherosclerosis. Azalanstat (RS-21607), a synthetic imidazole, has been shown to inhibit cholesterol synthesis in HepG2 cells, human fibroblasts, hamster hepatocytes and hamster liver, by inhibiting the cytochrome P450 enzyme lanosterol 14 alpha-demethylase. When administered orally to hamsters fed regular chow, RS-21607 (50 mg/kg/day) lowered serum cholesterol in a dose-dependent manner (ED50 = 62 mg/kg) in a period of 1 week. It preferentially lowered low density lipoprotein (LDL) cholesterol and apo B relative to high density lipoprotein (HDL) cholesterol and apo A-1. It also lowered plasma cholesterol levels in hamsters fed a high saturated fat and cholesterol diet. RS-21607 inhibited hepatic microsomal hydroxymethylglutaryl-CoA (HMG-CoA) reductase activity in hamsters in a dose-dependent manner (ED50 = 31 mg/kg), and this was highly correlated with serum cholesterol lowering (r = 0.97). Cholesterol lowering by azalanstat and cholestyramine was additive, and the increase in HMG-CoA reductase brought about by cholestyramine was attenuated significantly by azalanstat. In vitro studies with HepG2 cells indicated that this modulation of reductase activity was indirect, occurring at a post-transcriptional step, and it is proposed that a regulatory oxysterol derived from dihydrolanosterol (or lanosterol) may be responsible for this regulation. Azalanstat does not appear to lower circulating cholesterol in the hamster by up-regulation of the hepatic LDL receptor, suggesting that other mechanisms are involved. Orally administered azalanstat (50-75 mg/kg) stimulated hepatic microsomal cholesterol 7 alpha-hydroxylase activity by 50-400% in hamsters, and it is postulated that this may result from modified cholesterol absorption and bile acid synthesis.

First results of a clinical pilot study on intraarterial chemotherapy with haemofiltration of locally advanced gastrointestinal cancers.

Intra-arterial chemotherapy combined with haemofiltration enables the administration of drugs to confined neoplastic tissue while limiting the systemic drug exposure. During the procedure, the cytotoxic drugs are injected into the arterial supply of the tumour and the venous blood coming from the tumour bed is pumped out and filtered trough haemofiltration unit in order to extract the cytotoxic drug not fixed on the tumour. The patients selected for such treatment failed previous intravenous chemotherapy. Thirteen patients underwent intra-arterial chemotherapy injections combined with haemofiltration procedures: 8 unresectable liver metastases from colorectal cancer and 5 pelvic recurrences from rectal cancer. Fluorouracil, mitomycin C and doxorubicin were infused. One out of thirteen patients presented a complete regression of his liver metastases, 5/13 presented a partial regression, 2/13 patients did not show any significant modification of the size of their lesions and were classified as stable disease, 5/13 patients showed a progression of their neoplastic disease. No nephrotoxicity or major gastrointestinal side effects were observed. Intra-arterial chemotherapy combined with haemofiltration procedure is a therapeutic modality that could be considered in patients with locally advanced cancer who failed previous first line intravenous chemotherapy.

Diastolic dysfunction and severity of cirrhosis in nonalcoholic cirrhotic patients.

Background. In this study, we evaluated the association between diastolic dysfunction severity and severity of cirrhosis in nonalcoholic cirrhotic patients. Methods. This cross-sectional study was conducted on all nonalcoholic cirrhotic patients who were admitted in Rasht Razi hospital the Cancer of Guilan Province, north of Iran, from January 2011 to March 2012. Severity of cirrhosis was evaluated by Child-Pugh score. A 12-lead surface ECG and echocardiographic studies were performed. We used a HDI 3000 (Philips ATL, Bothell, WA, USA) equipped with 2 to 4 MHz probes. Diastolic function was determined by an expert cardiac sonographer. Data were analyzed by SPSS for win (version16). A P value less than 0.05 was considered significant. Results. Sixty-tree percent of patients were male. The mean age of patients was 52.78 ± 15.2 years. 22%, 38%, and 40% of patients were considered as child class A, B, and C, respectively. There was a significant relation between diastolic dysfunction and disease duration (P = 0.001), female gender (P = 0.004), age > 60 years (P = 0.045), and severity of cirrhosis (P = 0.048). On multivariate analysis, decreased E/A ratio (P = 0.03) and disease duration (P = 0.02) showed an independent significant relation. Conclusion. According to the relation between severity of cirrhosis and diastolic dysfunction, we recommend cardiac assessment in all child B and C cirrhotic patients.

The survey of diastolic function changes in end-stage renal disease patients before and 3 and 6 months after kidney transplantation.

INTRODUCTION: Left ventricular diastolic dysfunction, which is prevalent in end-stage renal disease, predicts morbidity and mortality among affected patients. The aim of this study was to evaluate diastolic function changes in end-stage renal disease patients before as well as 3 and 6 months after kidney transplantation. METHODS AND MATERIALS: This longitudinal study from November 2008 to November 2009, enrolled 27 consecutive kidney transplant patients. Systolic and diastolic blood pressures and echocardiograghic parameters such as ejection fraction, left ventricular mass, and diastolic functions were measured before, as well as 3 and 6 months after transplantation. Data were analyzed by repeated-measure analysis of variance and Friedman tests using SPSS version 18. RESULTS: The mean patients age was 39.47 ± 12.27 years with 55.6% males. The mean systolic and diastolic blood pressure and left ventricular mass decreased significantly in the first 3 (125.44 ± 11.35, 78.51 ± 6.32, 141.94 ± 3.32) and 6 months (121.48 ± 10.63, 72.96 ± 4.21, 138.25 ± 3.12) after renal transplantation compared to the values before the procedure (136.77 ± 14.09, 81.92 ± 9.01, 158.30 ± 3.58 respectively; P < .05). The left ventricular ejection fraction increased significantly at 3 (63.00 ± 6.49) and 6 months (66.11 ± 5.87) compared with preoperative (62.48 ± 5.74; P < .05). Step mean diastolic function also decreased significantly at 3 (1.94) and 6 months (1.81) compared with before transplantation (2.24; P < .05). CONCLUSION: According to our findings, transplantation can correct ejection fraction and systolic and diastolic blood pressure and lead to regression of left ventricular hypertrophy. Diastolic function was improved after transplantation.

Derivatization of peptides to enhance ionization efficiency and control fragmentation during analysis by fast atom bombardment tandem mass spectrometry.

Novel and simple procedures for preparing ethyl-triphenylphosphonium derivatives of peptides are described. These procedures allow an ethyl-triphenylphosphonium moiety to be selectively attached to either the N- or C-terminus. The resulting derivatives contain a positive charge at a fixed position and have significant hydrophobic character. Modification of peptides by these chemical methods significantly enhances the efficiency of fast atom bombardment ionization, especially of hydrophilic peptides. Moreover, upon collisionally activated dissociation, the derivatized peptides generate a predictable series of sequence ions from either the C-terminus or the N-terminus, depending on the location of the ethyl-triphenylphosphonium moiety.