Objective: To investigate the possible mechanism and the compound(s) responsible for the antiplatelet and acetylcholinesterase (AChE) inhibitory effects of Areca catechu crude extract (Ac.Cr). Methods: Aqueous-methanol (70%) was used for extraction of plant material (betel nut). Antiplatelet activity was measured in human platelet-rich plasma by using a Lumi-aggregometer while anti-AChE activity was measured spectrophotometrically in vitro. In an attempt to find the responsible compound(s) in betel nut for antiplatelet and anti-AChE activities, different commercially available betel nut compounds were tested. Results: Ac.Cr inhibited platelet aggregation induced by arachidonic acid (AA), adenosine diphosphate (ADP), platelet-activating factor (PAF), epinephrine and Ca(2+)-ionophore. Ac.Cr was the most potent in inhibiting ADP- and Ca(2+)-ionophore-induced aggregation. In the AChE assay, Ac.Cr showed significant AChE inhibitory activity with almost complete inhibition of the enzyme. Out of the tested compounds, none of the compounds in betel nut showed any antiplatelet effect except for catechin that was the most potent against epinephrine-induced aggregation. Catechin was significantly less potent than Ac.Cr, indicating a presence of additional compound(s) with antiplatelet activity. For the AChE inhibitory effect, only tannic acid, gallic acid, diosgenin and isoguvacine were found to be active, whereby tannic acid was more potent than Ac.Cr. Conclusion: This study shows the possible antiplatelet and AChE inhibitory potential of betel nut while further studies are needed to confirm and identify more compounds in betel nut for these actions.

Microorganisms adhere to non-living material or living tissue, and form biofilms made up of extracellular polymers/slime. Biofilm-associated microorganisms behave differently from free-floating bacteria with respect to growth rates and ability to resist antimicrobial treatments and therefore pose a public health problem. The objective of this study is to detect the prevalence of biofilm producers among Gram positive and Gram negative bacteria isolated from clinical specimens, and to study their antimicrobial susceptibility pattern. The study was carried out from October 2009 to March 2010, at the Department of Microbiology, Army Medical College/ National University of Sciences and Technology (NUST), Rawalpindi, Pakistan. Clinical specimens were received from various wards of a tertiary care hospital. These were dealt by standard microbiological procedures. Gram positive and Gram negative bacteria isolated were subjected to biofilm detection by congo red agar method (CRA). Antimicrobial susceptibility testing of those isolates, which showed positive results (slime production), was done according to the Kirby-Bauer disc diffusion technique. A total of 150 isolates were tested for the production of biofilm/slime. Among them, 81 isolates showed positive results. From these 81, 51 were Gram positive and 30 were Gram negative. All the 81(54%) slime producers showed reduced susceptibility to majority of antibiotics. Bacterial biofilms are an important virulence factor associated with chronic nosocomial infection. Detection of biofilm forming organisms can help in appropriate antibiotic choice.

The neurofilament proteins (NFPs) from different neuronal tissues including Alzheimer and Huntington disease gray matter, rat brain gray, white matter and spinal cord were separated biochemically into two major fractions. A systematic investigation on the distribution, expression and phosphorylation of NFPs in those fractions was undertaken in the present study. It was found that only non-phosphorylated NF-H and NF-M, but not NF-L subunit were detected in Alzheimer brain gray matter high speed supernatant, whereas all neurofilament subunits including non-phosphorylated and phosphorylated were measured in high speed pellet fraction of the same tissue. The hyperphosphorylation of NF-H and NF-M in Alzheimer brain was shown by phosphorylation dependent monoclonal antibodies SMI31 and SMI34. This hyperphosphorylation was confirmed by non-phosphorylation dependent antibody SMI32 with dephosphosphorylation of the samples. Furthermore, an increased amount of NF-H, NH-M and NF-L, detected by SMI33 and NR4 respectively, was also observed in Alzheimer samples, in which the elevation in NF-L was significant. A significantly different immunoblot patterns in distribution, expression and phosphorylation were determined in various position of the neural system and alternative fractions. To our best knowledge, this is the first data shown definite abnormality of NFPs in Alzheimer disease. The information obtained in the present study will be extremely valuable in further study of the proteins both in physiological and pathological conditions.

OBJECTIVETo explore the association between the abnormal phosphorylation sites found in Alzheimer disease (AD) tau and the inhibition of its biological activity.

METHODSUltracentrifugation, chromatography, manual Edman degradation and autosequence techniques were used to prepare and phosphorylate human recombinant tau, isolate and purify 32P tau peptides and determine phosphorylation sites.

RESULTSPhosphorylation of tau by casein kinase 1 (CK-1), cyclic AMP-dependent protein kinase (PKA) and glycogen synthetase kinase 3 (GSK-3) separately inhibited its biological activity and the inhibition of this activity by (CSK-3 was significantly increased if tau was prephosphorylated by CK-1 or PKA. The most potent inhibition was seen by a combined phosphorylation of tau with PKA and GSK-3. The treatment of tau by PKA and GSK-3 combination induced phosphorylation of tau at Ser-195, Ser-198, Ser-199, Ser-202, Thr-205, Thr-231, Ser-235, Ser-262, Ser-356, Ser-404, whereas Thr-181, Ser-184, Ser-262, Ser-356 and Ser-400 were phosphorylated by GSK-3 alone under the same condition.

CONCLUSIONPhosphorylation of tau by PKA plus GSK-3 at Thr-205 might play a key role in tau pathology in AD.

Alzheimer Disease ; metabolism ; Binding Sites ; Casein Kinases ; Cyclic AMP-Dependent Protein Kinases ; metabolism ; Glycogen Synthase Kinase 3 ; metabolism ; Humans ; In Vitro Techniques ; Microtubules ; metabolism ; Phosphorylation ; Protein Kinases ; metabolism ; tau Proteins ; metabolism

Hypertension is one of the most prevalent diseases in the developed and developing countries. Based on the long historical association and the provocative findings of blood pressure effects at low level of lead exposure a study was carried out to determine if an association existed between low blood lead concentration and hypertension. In this study the effects of low-level exposure to lead on blood pressure were examined among 244 adults using atomic absorption spectrometer. For quality assurance purpose certified reference materials i.e., Animal blood A-13, Bovine liver 1577 and cotton cellulose V-9 from IAEA (International Atomic Energy Agency) and NIST (National Institute of Standard Technology) were analyzed under identical experimental conditions. The mean age of hypertensive adults was 52 years (range 43 - 66). The mean values of systolic and diastolic blood pressure were (209+/-11.7) (range 170 - 250) and (117+/-3.9) (range 105 - 140) mmHg respectively. Blood lead concentration ranged from 78 - 201 microg/L with a mean of 139 microg/L and 165 - 497 microg/L with a mean of 255 microg/L in normal and hypertensive adults respectively. Increase in systolic blood pressure was significantly predictive with increase in blood lead levels. Body mass index (BMI) and lipid profile including total cholesterol, low density lipoprotein cholesterol, high density lipoprotein cholesterol and triglyceride correlated with blood pressure.
Adult ; Blood Pressure ; drug effects ; Body Mass Index ; Cholesterol ; blood ; Environmental Exposure ; Female ; Humans ; Hypertension ; chemically induced ; Lead ; blood ; toxicity ; Male ; Middle Aged ; Occupational Exposure

This study is aimed at identifying and determining the percentage of occurrence frequency of cellulose decomposing soil fungi. The soil samples were inoculated into culture plates prepared in Sabouraud medium under sterilized conditions and incubated at 30 degrees C for 4 to 7 d. The identified fungal species were incubated in self-designed cellulose medium for testing their cellulolytic ability. Forty-two species, including 2 nova species, representing sixteen genera showed growth and sporulation in the cellulose medium. Most of the isolated species were from genus Aspergillus and Penicillium. Aspergillus niger and Mucor hiemalis showed highest occurrence frequency (45% and 36% respectively), as these species were collected from about 80% of soil samples. Being agar free and cheaper, the new fungal medium designed showed results equivalent to Sabouraud medium.
Aspergillus ; isolation & purification ; metabolism ; Cellulose ; metabolism ; Culture Media ; Mitosporic Fungi ; classification ; isolation & purification ; metabolism ; Penicillium ; isolation & purification ; metabolism ; Soil Microbiology

Objective: To investigate the pharmacological potential of Argemone mexicana in treating constipation and emesis by using in vitro and in vivo models.Methods: The spasmogenic and spasmolytic effects were evaluated on isolated rabbit jejunum fragments loaded in a tissue organ bath. The response was recorded with an isotonic transducer attached with Power Lab Data Acquisition System. The laxative and antiemetic activities were assessed in BALB-c mice and poultry chicks challenged with carbamylcholine and copper sulphate stimulated emesis, respectively. Results: The total phenolic and total flavonoids contents of the extract were (267.75 ± 5.77) mg GAE/g and (73.86 ± 6.01) mg QE/g, respectively. Argemone mexicana extract exerted spasmogenic effect on isolated rabbit jejunum segments with an EC50 value of 0.016 mg/mL, which was blocked by atropine (0.3 μM). Argemone mexicana extract exerted spasmolytic effect in atropine treated jejunum fragments with an EC50 value of 2.185 mg/mL. Furthermore, Argemone mexicana extract relaxed potassium (80 mM)-induced contractions (EC50: 9.07 mg/mL), similar to a standard drug verapamil. The calcium channel blocker activity was confirmed by a rightward shift of concentration-response curve of calcium in the presence of Argemone mexicana extract (1-5 mg/mL) and verapamil (0.1-1 μM). In addition, the extract increased the distance travelled by a charcoal in the gastrointestinal tract and exhibited antiemetic effect on copper sulphate induced emesis in chicks. Conclusions: Argemone mexicana shows cholinergic agonist and calcium channel blocker activities, as well as antiemetic effect. It may be used as a potential agent for treating gastrointestinal disorders.

Tibial dyschondroplasia (TD) cases has not been reported in Tibetan chickens (TBCs), but it is commonly seen in commercial broilers characterized by lameness. The underlying mechanism remains unclear. Hypoxia-inducible factors (HIFs) are important regulators of cellular adaptation to hypoxic conditions. In this study, we investigated the role of HIF-1α,
Anoxia ; Blotting, Western ; Chickens ; Growth Plate ; Osteochondrodysplasias ; Poultry ; Reverse Transcriptase Polymerase Chain Reaction ; RNA ; Thiram

Background: and Purpose The association of dyslipidemia with stroke has been inconsistent, which may be due to differing associations within etiological stroke subtypes. We sought to determine the association of lipoproteins and apolipoproteins within stroke subtypes. Methods: Standardized incident case-control STROKE study in 32 countries. Cases were patients with acute hospitalized first stroke, and matched by age, sex and site to controls. Concentrations of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A1 (apoA1), and apoB were measured. Non-HDL-C was calculated. We estimated multivariable odds ratio (OR) and population attributable risk percentage (PAR%). Outcome measures were all stroke, ischemic stroke (and subtypes), and intracerebral hemorrhage (ICH). Results: Our analysis included 11,898 matched case-control pairs; 77.3% with ischemic stroke and 22.7% with ICH. Increasing apoB (OR, 1.10; 95% confidence interval [CI], 1.06 to 1.14 per standard deviation [SD]) and LDL-C (OR, 1.06; 95% CI, 1.02 to 1.10 per SD) were associated with an increase in risk of ischemic stroke, but a reduced risk of ICH. Increased apoB was significantly associated with large vessel stroke (PAR 13.4%; 95% CI, 5.6 to 28.4) and stroke of undetermined cause. Higher HDL-C (OR, 0.75; 95% CI, 0.72 to 0.78 per SD) and apoA1 (OR, 0.63; 95% CI, 0.61 to 0.66 per SD) were associated with ischemic stroke (and subtypes). While increasing HDL-C was associated with an increased risk of ICH (OR, 1.20; 95% CI, 1.14 to 1.27 per SD), apoA1 was associated with a reduced risk (OR, 0.80; 95% CI, 0.75 to 0.85 per SD). ApoB/A1 (OR, 1.38; 95% CI, 1.32 to 1.44 per SD) had a stronger magnitude of association than the ratio of LDL-C/HDL-C (OR, 1.26; 95% CI, 1.21 to 1.31 per SD) with ischemic stroke (P<0.0001). Conclusions The pattern and magnitude of association of lipoproteins and apolipoproteins with stroke varies by etiological stroke subtype. While the directions of association for LDL, HDL, and apoB were opposing for ischemic stroke and ICH, apoA1 was associated with a reduction in both ischemic stroke and ICH. The ratio of apoB/A1 was the best lipid predictor of ischemic stroke risk.

Objective: To investigate the pharmacological potential of Argemone mexicana in treating constipation and emesis by using in vitro and in vivo models. Methods: The spasmogenic and spasmolytic effects were evaluated on isolated rabbit jejunum fragments loaded in a tissue organ bath. The response was recorded with an isotonic transducer attached with Power Lab Data Acquisition System. The laxative and antiemetic activities were assessed in BALB-c mice and poultry chicks challenged with carbamylcholine and copper sulphate stimulated emesis, respectively. Results: The total phenolic and total flavonoids contents of the extract were (267.75 ± 5.77) mg GAE/g and (73.86 ± 6.01) mg QE/g, respectively. Argemone mexicana extract exerted spasmogenic effect on isolated rabbit jejunum segments with an EC50 value of 0.016 mg/mL, which was blocked by atropine (0.3 μM). Argemone mexicana extract exerted spasmolytic effect in atropine treated jejunum fragments with an EC50 value of 2.185 mg/mL. Furthermore, Argemone mexicana extract relaxed potassium (80 mM)-induced contractions (EC50: 9.07 mg/mL), similar to a standard drug verapamil. The calcium channel blocker activity was confirmed by a rightward shift of concentration-response curve of calcium in the presence of Argemone mexicana extract (1-5 mg/mL) and verapamil (0.1-1 μM). In addition, the extract increased the distance travelled by a charcoal in the gastrointestinal tract and exhibited antiemetic effect on copper sulphate induced emesis in chicks. Conclusions: Argemone mexicana shows cholinergic agonist and calcium channel blocker activities, as well as antiemetic effect. It may be used as a potential agent for treating gastrointestinal disorders.