Publications by authors named "Naveed Aslam"

22 Publications

  • Page 1 of 1

Serotonin-release assay-positive but platelet factor 4-dependent enzyme-immunoassay negative: HIT or not HIT?

Am J Hematol 2021 Mar 29;96(3):320-329. Epub 2020 Dec 29.

Department of Medicine, Michael G. DeGroote School of Medicine, Hamilton, Ontario, Canada.

IgG-specific and polyspecific PF4-dependent enzyme-immunoassays (EIAs) have exceptionally high sensitivity (≥99%) for diagnosis of heparin-induced thrombocytopenia (HIT), a drug reaction caused by platelet-activating antibodies detectable by serotonin-release assay (SRA). The IgG-specific EIAs are recommended for screening, as their high sensitivity is accompanied by relatively high specificity vis-à-vis polyspecific EIAs. We investigated the frequency of SRA-positive/EIA-negative (SRA+/EIA-) HIT, prompted by referral to our reference HIT laboratory of serial blood samples from a patient ("index case") with false-negative IgG-specific EIAs. Despite initial clinical suspicion for HIT, repeat negative IgG-specific EIAs prompted heparin resumption, which triggered recurrent thrombocytopenia and near-fatal cardiac arrest, indicating likely post-heparin HIT-associated anaphylactoid reaction. Further investigations revealed a strong-positive SRA, whether performed with heparin alone, PF4 alone, or PF4/heparin, with inhibition by Fc receptor-blocking monoclonal antibody (indicating IgG-mediated platelet activation); however, five different IgG-specific immunoassays yielded primarily negative (or weak-positive) results. To investigate the frequency of SRA+/EIA- HIT, we reviewed the laboratory and clinical features of patients with this serological profile during a 6-year period in which our reference laboratory investigated for HIT using both SRA and IgG-specific EIA. Although ~0.2% of 8546 patients had an SRA+/EIA- profile, further review of 15 such cases indicated clerical/laboratory misclassification or false-positive SRA in all, with no SRA+/EIA- HIT case identified. We conclude that while SRA+/EIA- HIT is possible-as shown by our index case-this clinical picture is exceptionally uncommon. Moreover, the requirement for a positive EIA is a useful quality control maneuver that reduces risk of reporting a false-positive SRA result.
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http://dx.doi.org/10.1002/ajh.26075DOI Listing
March 2021

Pharmacological evaluation of analgesic, anti-inflammatory and antipyretic activities of ethanolic extract of Indigofera argentea Burm. f.

J Ethnopharmacol 2020 Sep 11;259:112966. Epub 2020 May 11.

Department of Physiology and Pharmacology, University of Agriculture, Faisalabad, Pakistan. Electronic address:

Ethnopharmacological Relevance: Indigofera argentea Burm. f.; commonly known as neel, jantari, hathio; is traditionally used for the treatment of headache, fever, inflammation and body pain. Local communities also used this plant for the treatment of malaria, jaundice, vertigo and gastric disorders.

Aim Of The Study: This study is aimed to evaluate the toxicity and possible analgesic, anti-inflammatory and antipyretic activities of the ethanolic crude extract of Indigofera argentea (IaCr) to support its use in folk medicine and to screen the phytochemical constituents and antioxidant activity.

Materials And Methods: Aqueous ethanolic (30:70) extract of whole plant of Indigofera argentea (IaCr) was prepared and phytochemical study was performed by preliminary methods followed by HPLC and DPPH method. In vivo experiments were performed in Wistar albino rats including hot plate, tail immersion, formalin and capsaicin-induced pain tests in rats and acetic acid-induced writhing test in mice. Anti-inflammatory activity was assessed by using in vitro human red blood cell (HRBC) membrane stabilization and carrageenan-induced rat paw edema test, while antipyretic activity was evaluated by Brewer's yeast-induced pyrexia test.

Results: The crude extract of Indigofera argentea confirmed the presence of flavonoids, glycosides, alkaloids, saponins and tannins as soluble ethanolic constituents in preliminary study. The maximum quantity of gallic acid equivalent (GAE) phenolics, and quercetin equivalent (QE) flavonoid content found was 81 ± 2 mg GAE/g and 56 ± 1.4 mg QE/g of extract respectively. Quantification based on HPLC exposed the presence of phenols and flavonoids, quercetin, gallic acid, caffeic acid, chlorogenic acid, benzoic acid, ferulic acid and coumaric acid. In vivo experiments revealed significant P < 0.05) dose-dependent inhibition in hot plate, tail immersion and capsaicin-induced pain test. IaCr showed significant inhibition of pain latency against both phases in formalin test and considerably decreased the number of writhes caused by acetic acid at the doses of 30, 100 and 300 mg/kg. In the in vitro anti-inflammatory (HRBC) assay, IaCr showed good membrane stability with maximum percentage hemolysis inhibition of 49.29% while in carrageenan-induced paw edema test in rats the IaCr showed significant anti-inflammatory action in a dose-dependent fashion. Statistical significant reduction in rectal temperature was observed at the doses of 100 and 300 mg/kg in yeast-induced pyrexia test in rats.

Conclusion: The results of the experimental studies proved the analgesic, anti-inflammatory and antipyretic activities of Indigofera argentea and supported the traditional use of this plant.
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http://dx.doi.org/10.1016/j.jep.2020.112966DOI Listing
September 2020

Increase in PKCα Activity during Heart Failure Despite the Stimulation of PKCα Braking Mechanism.

Authors:
Naveed Aslam

Int J Mol Sci 2020 Apr 7;21(7). Epub 2020 Apr 7.

BioSystOmics 4424 Jim West Street, Bellaire, TX 77401, USA.

Heart failure (HF) is marked by dampened cardiac contractility. A mild therapeutic target that improves contractile function without desensitizing the β-adrenergic system during HF may improve cardiac contractility and potentially survival. Inhibiting protein kinase C α (PKCα) activity may fit the criteria of a therapeutic target with milder systemic effects that still boosts contractility in HF patients. PKCα activity has been observed to increase during HF. This increase in PKCα activity is perplexing because it is also accompanied by up-regulation of a molecular braking mechanism. I aim to explore how PKCα activity can be increased and maintained during HF despite the presence of a molecular braking mechanism. Using a computational approach, I show that the local diacylglycerol (DAG) signaling is regulated through a two-compartment signaling system in cardiomyocytes. These results imply that after massive myocardial infarction (MI), local homeostasis of DAG signaling is disrupted. The loss of this balance leads to prolonged activation of PKCα, a key molecular target linked to LV remodeling and dysfunctional filling and ejection in the mammalian heart. This study also proposes an explanation for how DAG homeostasis is regulated during normal systolic and diastolic cardiac function. I developed a novel two-compartment computational model for regulating DAG homeostasis during Ang II-induced heart failure. This model provides a promising tool with which to study mechanisms of DAG signaling regulation during heart failure. The model can also aid in identification of novel therapeutic targets with the aim of improving the quality of life for heart failure patients.
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http://dx.doi.org/10.3390/ijms21072561DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177253PMC
April 2020

Simplified Model of PKCγ Signaling Dysregulation and Cytosol-to-Membrane Translocation Kinetics During Neurodegenerative Spinocerebellar Ataxia Type 14 (SCA14).

Front Neurosci 2019 31;13:1397. Epub 2020 Jan 31.

BioSystOmics, Bellaire, TX, United States.

Spinocerebellar ataxia type 14 (SCA14) is an autosomal neurodegenerative disease clinically characterized by progressive ataxia in the patient's gait, accompanied by slurred speech and abnormal eye movements. These symptoms are linked to the loss of Purkinje cells (PCs), which leads to cerebellar neurodegeneration. PC observations link the mutations in PRKCG gene encoding protein kinase C γ (PKCγ) to SCA14. Observations also show that the link between PKCγ and SCA14 relies on a gain-of-function mechanism, and, in fact, both positive and negative regulation of PKCγ expression and activity may result in changes in cellular number, size, and complexity of the dendritic arbors in PCs. Here, through a systems biology approach, we investigate a key question relating to this system: why is PKCγ membrane residence time reduced in SCA14 mutant PCs compared to wild-type (WT) PCs? In this study, we investigate this question through two contrasting PKCγ signaling models in PCs. The first model proposed in this study describes the mechanism through which PKCγ signaling activity may be regulated in WT PCs. In contrast, the second model explores how mutations in PKCγ signaling affect the state of SCA14 in PCs. Numerical simulations of both models show that, in response to extracellular stimuli-induced depolarization of the membrane compartment, PKCγ and diacylglycerol kinase γ (DGKγ) translocate to the membrane. Results from our computational approach indicate that, for the same set of parameters, PKCγ membrane residence time is shorter in the SCA14 mutant model compared to the WT model. These results show how PKCγ membrane residence time is regulated by diacylglycerol (DAG), causing translocated PKCγ to return to the cytosol as DAG levels drop. This study shows that, when the strength of the extracellular signal is held constant, the membrane lifetime of mutant PKCγ is reduced. This reduction is due to the presence of constitutively active mutant PKCγ in the cytosol. Cytosolic PKCγ, in turn, leads to phosphorylation and activation of DGKγ while it is still residing in the cytosol. This effect occurs even during the resting conditions. Thus, the SCA14 mutant model explains that, when both DAG effector molecules are active in the cytosol, their interactions in the membrane compartment are reduced, critically influencing PKCγ membrane residence time.
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http://dx.doi.org/10.3389/fnins.2019.01397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004970PMC
January 2020

Prospective nonrandomized study with early steroid withdrawal (Day 5) postrenal transplant in low immunological risk patients: A singlecenter experience at prince sultan military medical city Riyadh.

Saudi J Kidney Dis Transpl 2019 Nov-Dec;30(6):1398-1406

Department of Nephrology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia.

Steroids remain an essential part of immunosuppressive therapy for renal transplant patients since the start of transplant era. Different immunosuppressive regimens are prescribed so as to minimize the side effects. The purpose of our study is to compare the outcome of early steroid withdrawal with steroid maintenance protocol. It is a prospective nonrandomized study. All patients that received renal transplants from January 2011 to December 2013 were included in the study. Early steroid withdrawal at day 5 was done in low immunological risk patients, and the results were compared with the steroid maintenance group, at one-year, posttransplant. Outcome measures included acute rejection (AR), slow graft function and delayed graft function (SGF and DGF), patient and graft survival, and new-onset diabetes after transplant (NODAT), dyslipidemia, hypertension, and obesity. A total of 249 patients were divided into two groups - 105 patients had early steroid withdrawal and 144 patients were maintained on steroid therapy. Outcome measures were compared one-year posttransplant. There was no significant difference in AR, patient and graft survival, creatinine level, and weight gain. However, a significant difference in systolic and diastolic blood pressure, lipid profile, NODAT, SGF, and DGF was found in the steroid group. Our study shows that early steroid withdrawal is a safe standard of care in low immunological risk patients.
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http://dx.doi.org/10.4103/1319-2442.275484DOI Listing
August 2020

Studies on antidiarrheal and laxative activities of aqueous-ethanol extract of Asphodelus tenuifolius and underlying mechanisms.

BMC Complement Altern Med 2019 Nov 11;19(1):307. Epub 2019 Nov 11.

Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, 60800, Pakistan.

Background: Asphodelus tenuifolius Cav. (Asphodelaceae) has traditional reputability in treatment of diarrhea and constipation but no scientific study has been reported for its gastrointestinal effects. Present study was conducted to evaluate antidiarrheal and laxative activities of the plant.

Methods: Aqueous-ethanol crude extract of Asphodelus tenuifolius (At.Cr) was subjected to phytochemical screening and liquid-liquid fractionation. In vivo studies of charcoal meal intestinal transit test, antidiarrheal activity against castor oil induced diarrhea and laxative activity were performed in mice. In vitro experiments were conducted upon rabbit jejunum preparations using standard tissue bath techniques.

Results: Phytochemical screening indicated presence of alkaloids, anthraquinones, flavonoids, saponins, steroids, tannins and phenols in At.Cr. In charcoal meal intestinal transit test, At.Cr increased (p < 0.001) intestinal motility at 100 mg/kg dose, but decreased (p < 0.001) it at 500 mg/kg dose, when compared to the control group. At.Cr (300-700 mg/kg) provided protection from castor oil induced diarrhea in mice, which was significant (p < 0.001) at 500 and 700 mg/kg doses, as compared to the saline treated control group. At.Cr (50 and 100 mg/kg) enhanced total and wet feces counts in normal mice, as compared to saline treated control. In jejunum preparations, At.Cr inhibited spontaneous, K (80 mM) and K (25 mM) mediated contractions, similar to verapamil. Pre-incubation of jejunum preparations with At.Cr resulted in rightward nonparallel shift in Ca concentration response curves, similar to verapamil. The spasmolytic activity was concentrated in ethylacetate fraction. Aqueous fraction exhibited spasmogenicity upon spontaneous contractions, which was blocked in presence of verapamil, but remained unaffected by other tested antagonists.

Conclusion: The Asphodelus tenuifolius crude extract possesses gut modulatory activity, which may normalize gut functions in diarrhea and constipation. The spasmolytic activity of the extract was found to be mediated through Ca channel blocking action. The spasmogenic activity, found partitioned in aqueous fraction, possibly involves Ca influx through voltage gated Ca channels. The study supports ethnic uses of the plant in diarrhea and constipation.
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http://dx.doi.org/10.1186/s12906-019-2740-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6849252PMC
November 2019

Antidiabetic and antidyslipidemic potential of Echinops echinatus in rat models of type I and type II diabetes.

Pak J Pharm Sci 2019 Mar;32(2):505-514

Department of Neurosurgery, University Hospital Bonn, University of Bonn, Germany.

Echinops echinatus is traditionally an important plant that finds its extensive use as a diuretic, anti-inflammatory, anti-pyretic, nerve tonic, abortifacient, aphrodisiac, antiasthmatic, and antidiabetic agent. The current study investigates protection against the hyperglycemia and dyslipidemia in alloxan-induced (type I diabetes) and fructose-fed insulin resistance (type II diabetes) models of diabetes treated with aqueous methanolic root extract of E. echinatus (Ee.Cr). Albino rats were treated orally with Ee.Cr at doses 100, 300 and 500mg/kg. The fasting blood glucose was measured by glucometer, while standard kits were used to determine the levels of serum total cholesterol, triglycerides and HDL. The administration of Ee.Cr significantly (P<0.001) reduced the FBG concentration in a dose-dependent pattern in alloxan-induced and fructose-fed diabetic rats. The Ee.Cr also corrected the dyslipidemia associated with fructose and alloxan-induced diabetes by significantly (P<0.001) decreasing the concentration of serum total cholesterol, triglycerides, and LDL and by increasing HDL concentration. Ee.Cr also significantly (P<0.001) improved the glucose tolerance in fructose-fed rats. We conclude that Ee.Cr has antidiabetic and antidyslipidemic effects in both insulin-dependent alloxan-induced diabetes and fructose-induced insulin resistance diabetes rat models.
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March 2019

The Nutritional and Phytochemical Composition of the Indigenous Australian Pindan Walnut (Terminalia cunninghamii) Kernels.

Plant Foods Hum Nutr 2018 Mar;73(1):40-46

School of Public Health, Curtin University, Perth, Western Australia, 6102, Australia.

Nutritional composition of the kernels of two types of Pindan walnut (Terminalia cunninghamii), a native nut consumed traditionally by Australian Indigenous peoples, is reported for the first time. Results showed that Pindan walnut kernels contained high levels of fat, protein and ash, approximately 50, 30 and 5% fresh basis, respectively. The levels of minerals in the kernels were much higher than common walnuts and macadamia nuts, especially those of phosphorus, magnesium and zinc. The high amounts of polyphenols in the kernels provided strong hydrophilic antioxidant capacities, of up to 2004 mg Trolox equivalents/100 g fresh basis using the hydrophilic oxygen radical absorbance capacity assay. Both free polyphenol content and hydrophilic antioxidant capacities of the kernels were higher than those of macadamia nuts, although the lipophilic oxygen radical absorbance capacity was lower. These preliminary studies indicate high potential for wider use of the Pindan walnut as a novel, nutritious and health-promoting food.
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http://dx.doi.org/10.1007/s11130-017-0647-9DOI Listing
March 2018

Antispasmodic and bronchorelaxant activities of Salsola imbricata are mediated through dual Ca antagonistic and β-adrenergic agonistic effects.

Pharm Biol 2017 Dec;55(1):1131-1137

a Department of Pharmacy , Bahauddin Zakariya University , Multan , Pakistan.

Context: Salsola imbricata Forssk. (Chenopodiaceae) has folkloric repute for the treatment of various gastrointestinal and respiratory ailments.

Objective: The present study investigates spasmolytic and bronchorelaxant effects of S. imbricata.

Materials And Methods: The crude aqueous-ethanol extract of the aerial parts of S. imbricata and its fractions, in cumulative concentrations (0.01-10 mg/mL), were tested on contractions of isolated rabbit jejunum and tracheal preparations. Furthermore, concentration response curves (CRCs) of Ca and carbachol were constructed in the absence and presence of the extract. Standard organ bath methods were used.

Results: The crude extract relaxed spontaneous, K(80 mM) and carbachol (1 μM)-induced contractions in jejunum preparations with respective EC values of 0.40 (0.35-0.46), 0.69 (0.60-0.79) and 0.66 (0.57-0.75) mg/mL. It shifted Ca CRCs rightward in nonparallel manner. In isolated tracheal preparations, the crude extract caused relaxation of K(80 mM) and carbachol (1 μM)-induced contractions with EC values of 0.86 (0.75-0.98) and 0.74 (0.66-0.84) mg/mL, respectively. It displaced carbachol CRCs rightward with suppression of maximal response. In both tissues, pretreatment with propranolol (1 μM) caused rightward shift in inhibitory CRCs of the extract against carbachol-induced contractions. The ethyl acetate fraction was found more potent in relaxing smooth muscle contractions than the parent extract and its aqueous fraction.

Discussion And Conclusion: The results suggest that the spasmolytic and bronchorelaxant activities of S. imbricata are related to Ca antagonistic and β-adrenergic agonistic effects, thus justifying some of the traditional uses of the plant.
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http://dx.doi.org/10.1080/13880209.2017.1291691DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6130700PMC
December 2017

Higher Levels of Aflatoxin M1 Contamination and Poorer Composition of Milk Supplied by Informal Milk Marketing Chains in Pakistan.

Toxins (Basel) 2016 12 5;8(12). Epub 2016 Dec 5.

Graham Centre for Agricultural Innovation, Charles Sturt University, Wagga 2650, NSW, Australia.

The present study was conducted to observe the seasonal variation in aflatoxin M1 and nutritional quality of milk along informal marketing chains. Milk samples (485) were collected from three different chains over a period of one year. The average concentrations of aflatoxin M1 during the autumn and monsoon seasons (2.60 and 2.59 ppb) were found to be significantly higher (standard error of the difference, SED = 0.21: = 0.003) than in the summer (1.93 ppb). The percentage of added water in milk was significantly lower (SED = 1.54: < 0.001) in summer (18.59%) than in the monsoon season (26.39%). There was a significantly different (SED = 2.38: 0.001) mean percentage of water added by farmers (6.23%), small collectors (14.97%), large collectors (27.96%) and retailers (34.52%). This was reflected in changes in milk quality along the marketing chain. There was no difference ( = 0.178) in concentration of aflatoxin M1 in milk collected from the farmers (2.12 ppb), small collectors (2.23 ppb), large collectors (2.36 ppb) and retailers (2.58 ppb). The high levels of contamination found in this study, which exceed the standards set by European Union (0.05 ppb) and USFDA (0.5 ppb), demand radical intervention by regulatory authorities and mass awareness of the consequences for consumer health and safety.
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http://dx.doi.org/10.3390/toxins8120347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5198542PMC
December 2016

ANTIDIABETIC AND ANTIDYSLIPIDEMIC EFFECTS OF HELIOTROPIUM STRIGOSUM IN RAT MODELS OF TYPE I AND TYPE II DIABETES.

Acta Pol Pharm 2016 Nov;73(6):1575-1586

Heliotropiumz stnigosum Wilid. (Boraginaceae) is used traditionally as a laxative, diuretic, and as a treatment for snake bites and stings of nettles. Recent investigations have shown anti-inflammatory and antioxidant activity of H. sorigosum. However, antihyperglycemic and antidyslipidemic activity of H. strigosum has not been investigated to date and we aimed to explore these activities of the crude aqueous methanolic extract of thEaerial parts of H. strigosum (Hs.Cr). Hs.Cr was administered orally at doses of 100, 300, and 500 mg/kg in alloxan-induced diabetic rats (type I diabetes) and fructose-fed rats (type II diabetes). The fasting blood glucose (FBG) concentration was assessed by glucometer, while semum total cholesterol, triglycerides and HDL were estimated by using standard kits. The FBG concentration significantly (p < 0.05) decreased in dose-dependent pattern in both alloxan-induced diabetic and fructose-fed rats on Hs.Cr administration. The percentage glucose reductions in alloxanized rats with glibenclamide, Hs.Cr 100, 300, and 500 mg/kg were obeserved to be 67, 36, 56 and 62%, respectively. In fructose-fed rats, the percentage glucose redutions associated with metformin, Hs.Cr 100, 300, and 500 mg/kg were 23, 5, 11 and 12%, respectively. The extract also corrected the dyslipidemia associated with fructose and alloxan-induced diabetes by significantly (p < 0.00 1) decreasing the concentration of serum total cholesterol, triglycerides and LDL and by increasing HDL concentration. Our data demonstrate that the H. stigosum has antidiabetic and antidyslipidemic effects, thus encouraging further studies.
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November 2016

Sharp Central Venous Recanalization in Hemodialysis Patients: A Single-Institution Experience.

Cardiovasc Intervent Radiol 2016 Jun 16;39(6):927-34. Epub 2015 Dec 16.

Department of Nephrology, Prince Sultan Military Medical City (PSMMC), Riyadh, 11159, Kingdom of Saudi Arabia.

Purpose: We report our institutional experience with sharp central venous recanalization in chronic hemodialysis patients who failed standard techniques.

Materials And Methods: Since January 2014, a series of seven consecutive patients (four males and three females), mean age 35 years (18-65 years), underwent sharp central venous recanalization. Indications included obtaining hemodialysis access (n = 6) and restoration of superior vena cava (SVC) patency to alleviate occlusion symptoms and restore fistula function (n = 1). The transseptal needle was used for sharp recanalization in six patients, while it could not be introduced in one patient due to total occlusion of the inferior vena cava. Instead, transmediastinal SVC access using Chiba needle was obtained.

Results: Technical success was achieved in all cases. SVC recanalization achieved symptoms' relief and restored fistula function in the symptomatic patient. One patient underwent arteriovenous fistula creation on the recanalized side 3 months after the procedure. The remaining catheters were functional at median follow-up time of 9 months (1-14 months). Two major complications occurred including a right hemothorax and a small hemopericardium, which were managed by covered stent placement across the perforated SVC.

Conclusion: Sharp central venous recanalization using the transseptal needle is feasible technique in patients who failed standard recanalization procedures. The potential high risk of complications necessitates thorough awareness of anatomy and proper technical preparedness.
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http://dx.doi.org/10.1007/s00270-015-1270-5DOI Listing
June 2016

Hypotensive, Angiotensin Converting Enzyme (ACE) Inhibitory and Diuretic Activities of the Aqueous-methanol Extract of Ipomoea reniformis.

Iran J Pharm Res 2013 ;12(4):769-76

Faculty of Pharmacy and Alternative Medicine, Department of Pharmacy, the Islamia University of Bahawalpur, Pakistan.

Ipomoea reniformis Roxb. (Convolvulaceae) is a small, weedy herb used for the management of cardiac problems in traditional systems of medicine in India and Pakistan. Objective of the present study was to investigate the hypotensive, diuretic and angiotensin converting enzyme (ACE) inhibitory activities of the aqueous-methanol (30:70) crude extract of the dried aerial parts of I. reniformis (Ir.Cr.) in rats. To record blood pressure lowering effects of the Ir.Cr, different doses of the extract were administered through jugular vein to the ketamine-diazepam anesthetized normotensive rats and blood pressure was recorded via carotid artery. ACE inhibitory activity of the extract was studied in-vitro; using hippuryl-l-histidyl-l-leucine as substrate, the product hippurate was quantified spectrophotometrically after reacting with cyanuric chloride/dioxane reagent. Effects of intraperitoneal administration of the extract on urine and urinary electrolyte excretion were also investigated in rats. The extract (Ir.Cr.) produced 21.51 ± 3.41, 28.99 ± 2.30, 53.34 ± 0.88 and 61.71 ± 3.37% fall in mean arterial blood pressure of the anesthetized rats at the doses of 0.1, 0.3, 1.0 and 3.0 mg/Kg, respectively. Ir.Cr. was found to have serum ACE inhibitory activity, with IC50 value of 422 ± 21.16 μg/mL. The extract also increased urine volume and urinary Na(+) excretion significantly at the doses of 30 and 50 mg/Kg in rats. The study concludes that the crude extract of Ipomoea reniformis (Ir.Cr.) has hypotensive, ACE inhibitory and diuretic activities, which provide the scientific justification for the traditional uses of the plant as cardioprotective, antihypertensive and diuretic remedy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3920690PMC
February 2014

Evaluation of different milking practices for optimum production performance in Sahiwal cows.

J Anim Sci Technol 2014 7;56:13. Epub 2014 Aug 7.

Department of Animal Resources, International Research Center for Eradication of Poverty and Hunger, Daegu University, Gyeongsan, South Korea.

The production performance of multiparous lactating Sahiwal cows (n = 24) was evaluated according to both milking frequency and method. Selected animals were randomly divided into four groups containing six animals each under a completely randomized design. Cows in groups A & B were milked by the hand milking method three times per day, respectively. Similarly, cows in groups C & D were milked by the machine milking method two and three times per day, respectively. All animals were maintained under uniform feeding and management conditions. Dry matter intake was high in animal groups milked three times per day, and it remained unchanged between the hand and machine milking methods. Milk yield was higher (P < 0.05) in cows milked three times compared to those milked twice per day, and it did not differ between hand and machine milking methods. Milk fat percentage was higher (P < 0.05) in cows milked twice per day compared to those milked three times using both machine and hand milking methods. The percentage of total solids showed a similar pattern as the fat percentage. However, percentages of protein, lactose, and non-fat solids in milk were not significantly different (P > 0.05) among the treatment groups. Collectively, the results show that milking three times per day instead of twice at 8-hour intervals can enhance milk yield in Sahiwal cows using both hand and machine milking methods.
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http://dx.doi.org/10.1186/2055-0391-56-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4540307PMC
August 2015

A consensus map of rapeseed (Brassica napus L.) based on diversity array technology markers: applications in genetic dissection of qualitative and quantitative traits.

BMC Genomics 2013 Apr 23;14:277. Epub 2013 Apr 23.

EH Graham Centre for Agricultural Innovation (an alliance between NSWDPI and Charles Sturt University), Wagga Wagga Agricultural Institute, Wagga Wagga, NSW 2650, Australia.

Background: Dense consensus genetic maps based on high-throughput genotyping platforms are valuable for making genetic gains in Brassica napus through quantitative trait locus identification, efficient predictive molecular breeding, and map-based gene cloning. This report describes the construction of the first B. napus consensus map consisting of a 1,359 anchored array based genotyping platform; Diversity Arrays Technology (DArT), and non-DArT markers from six populations originating from Australia, Canada, China and Europe. We aligned the B. napus DArT sequences with genomic scaffolds from Brassica rapa and Brassica oleracea, and identified DArT loci that showed linkage with qualitative and quantitative loci associated with agronomic traits.

Results: The integrated consensus map covered a total of 1,987.2 cM and represented all 19 chromosomes of the A and C genomes, with an average map density of one marker per 1.46 cM, corresponding to approximately 0.88 Mbp of the haploid genome. Through in silico physical mapping 2,457 out of 3,072 (80%) DArT clones were assigned to the genomic scaffolds of B. rapa (A genome) and B. oleracea (C genome). These were used to orientate the genetic consensus map with the chromosomal sequences. The DArT markers showed linkage with previously identified non-DArT markers associated with qualitative and quantitative trait loci for plant architecture, phenological components, seed and oil quality attributes, boron efficiency, sucrose transport, male sterility, and race-specific resistance to blackleg disease.

Conclusions: The DArT markers provide increased marker density across the B. napus genome. Most of the DArT markers represented on the current array were sequenced and aligned with the B. rapa and B. oleracea genomes, providing insight into the Brassica A and C genomes. This information can be utilised for comparative genomics and genomic evolution studies. In summary, this consensus map can be used to (i) integrate new generation markers such as SNP arrays and next generation sequencing data; (ii) anchor physical maps to facilitate assembly of B. napus genome sequences; and (iii) identify candidate genes underlying natural genetic variation for traits of interest.
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http://dx.doi.org/10.1186/1471-2164-14-277DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641989PMC
April 2013

Regulation of cytoplasmic polyadenylation can generate a bistable switch.

BMC Syst Biol 2012 Feb 15;6:12. Epub 2012 Feb 15.

Department of Neurobiology and Anatomy, The University of Texas, Medical School, 6431 Fannin Street, Houston, Texas 77030, USA.

Background: Translation efficiency of certain mRNAs can be regulated through a cytoplasmic polyadenylation process at the pre-initiation phase. A translational regulator controls the polyadenylation process and this regulation depends on its posttranslational modifications e.g., phosphorylation. The cytoplasmic polyadenylation binding protein (CPEB1) is one such translational regulator, which regulates the translation of some mRNAs by binding to the cytoplasmic polyadenylation element (CPE). The cytoplasmic polyadenylation process can be turned on or off by the phosphorylation or dephosphorylation state of CPEB1. A specific example could be the regulation of Calcium/Calmodulin-dependent protein kinase II (αCaMKII) translation through the phosphorylation/dephosphorylation cycle of CPEB1.

Result: Here, we show that CPEB1 mediated polyadenylation of αCaMKII mRNA can result in a bistable switching mechanism. The switch for regulating the polyadenylation is based on a two state model of αCaMKII and its interaction with CPEB1. Based on elementary biochemical kinetics a high dimensional system of non-linear ordinary differential equations can describe the dynamic characteristics of the polyadenylation loop. Here, we simplified this high-dimensional system into approximate lower dimension system that can provide the understanding of dynamics and fixed points of original system. These simplified equations can be used to develop analytical bifurcation diagrams without the use of complex numerical tracking algorithm, and can further give us intuition about the parameter dependence of bistability in this system.

Conclusion: This study provides a systematic method to simplify, approximate and analyze a translation/activation based positive feedback loop. This work shows how to extract low dimensional systems that can be used to obtain analytical solutions for the fixed points of the system and to describe the dynamics of the system. The methods used here have general applicability to the formulation and analysis of many molecular networks.
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http://dx.doi.org/10.1186/1752-0509-6-12DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3359155PMC
February 2012

Tacrolimus versus cyclosporine for early steroid withdrawal after renal transplantation.

J Nephrol 2012 Jan-Feb;25(1):43-9

Division and Chair of Nephrology, University Hospital Spedali Civili, Brescia, Italy.

Introduction: This study compares cyclosporine (CsA) with tacrolimus (Tac) in preventing acute rejection (AR) after steroid withdrawal (SW) 5 days after renal transplantation (Tx).

Methods: The data were collected from 2 prospective sequential studies carried out from February 2002 to May 2006. Forty-nine patients received CsA, 56 patients Tac. Rapamycin (Rapa) was added to both calcineurin inhibitors (CNIs). The studies were homogeneous regarding both clinical procedures and patient demographics.

Results: Three years after SW, Tac was more effective than CsA in reducing the risk both of AR (35% vs. 53%; p<0.06) and mainly of relapses (9% vs. 33%; p<0.007). In addition, Tac enabled more patients to go onto a steroid-free regime (88% vs. 65%; p<0.01). No difference arose concerning the timing of AR, graft function, CNI withdrawal, incidence of side effects or patient and graft survival rates. In both groups, rejection after SW was associated with a worse graft function.

Conclusions: Tac was more effective than CsA in preventing AR after early SW, and increased significantly patient probability of maintaining a steroid-free regime. In this setting, Tac and CsA had the same safety profile. However, a follow-up longer than 3 years might be needed to estimate the consequences of the higher rate of AR encountered under CsA therapy.
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http://dx.doi.org/10.5301/jn.5000070DOI Listing
June 2012

The biosynthesis characteristics of TTP and TNF can be regulated through a posttranscriptional molecular loop.

J Biol Chem 2011 Feb 18;286(5):3767-76. Epub 2010 Nov 18.

Department of Neurobiology and Anatomy, University of Texas Medical School, Houston, Texas 77030, USA.

The abundant expression of tumor necrosis factor (TNF) is a hallmark of chronic inflammation of the gastrointestinal tract. Prolonged inflammation can lead to inflammatory bowel disease. TNF biosynthesis is regulated both at transcription and posttranscriptional levels. However, the stimulation-induced increase in translation rate is much larger. This might indicate the possibility of a posttranscriptional regulatory mechanism. How, during basal conditions, is the free concentration of TNF tightly regulated at low levels? The stability and translational efficiency of TNF transcript are regulated by an AU-rich element (ARE) in the 3'-UTR of messenger RNA. A transacting protein, TTP, binds to ARE and enhances the mRNA turnover. Here, we examine a proposal that TNF homeostasis is regulated by a TTP-TNF interaction loop at the posttranscriptional level. We propose a computational framework of this regulatory loop by modeling the role of AREs in mediating the messenger RNA stability and translation. This posttranscriptional regulatory loop between TTP and TNF is composed of two feedback loops (i.e. positive and negative). The mutual interaction of these feedback loops regulates the biosynthesis response of TNF during basal and inflammatory conditions. Here, we also propose an explanation for why the p38 inhibitors become insensitive for TTP knock-out mice.
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http://dx.doi.org/10.1074/jbc.M110.168757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030378PMC
February 2011

Translational switch for long-term maintenance of synaptic plasticity.

Mol Syst Biol 2009 16;5:284. Epub 2009 Jun 16.

Department of Neurobiology and Anatomy, The University of Texas Medical School at Houston, Houston, TX 77030, USA.

Memory can last a lifetime, yet synaptic contacts that contribute to the storage of memory are composed of proteins that have much shorter lifetimes. A physiological model of memory formation, long-term potentiation (LTP), has a late protein-synthesis-dependent phase (L-LTP) that can last for many hours in slices or even for days in vivo. Could the activity-dependent synthesis of new proteins account for the persistence of L-LTP and memory? Here, we examine the proposal that a self-sustaining regulation of translation can form a bistable switch that can persistently regulate the on-site synthesis of plasticity-related proteins. We show that an alpha CaMKII-CPEB1 molecular pair can operate as a bistable switch. Our results imply that L-LTP should produce an increase in the total amount of alpha CaMKII at potentiated synapses. This study also proposes an explanation for why the application of protein synthesis and alphaCaMKII inhibitors at the induction and maintenance phases of L-LTP result in very different outcomes.
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http://dx.doi.org/10.1038/msb.2009.38DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2710869PMC
September 2009

Unusual oropharyngeal foreign body.

J Coll Physicians Surg Pak 2008 Nov;18(11):719-20

Department of ENT, Head and Neck Surgery, Federal Postgraduate Medical Institute and Sheikh Zayed Hospital, Lahore, Pakistan.

We present an unusual case of foreign body (sewing needle) in a young man, who swallowed it with bolus of food. It penetrated through soft palate into parapharyngeal space, detected with image intensifier and removed successfully. Postoperative course remained uneventful.
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http://dx.doi.org/11.2008/JCPSP.719720DOI Listing
November 2008

Ciprofloxacin inhibits cell growth and synergises the effect of etoposide in hormone resistant prostate cancer cells.

Int J Oncol 2002 Jul;21(1):207-11

Department of Hematology/Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.

Prostate cancer is the most commonly diagnosed cancer and the second leading cause of cancer related deaths in men in the United States. Ciprofloxacin is a relatively non-toxic antibiotic that can be easily administered orally with large volume of distribution and good tissue penetration. Studies from others and our laboratory have recently reported its anti-tumor activity in a variety of human tumor cells. In our current experiment, we studied the effect of ciprofloxacin on a hormone resistant prostate cancer (HRPC) cell line, PC-3. Our study shows significant in vitro cell growth inhibition of PC-3 cell line (p=0.0001) and also shows that there is a synergistic increase in the antiproliferative effect of etoposide when these cells are pretreated with ciprofloxacin for 24 h, prior to etoposide exposure (p=0.0001). Western blot analysis of the protein extracts from these cells showed down-regulation of Bcl-2, altering the ratio of Bax:Bcl-2 favoring apoptosis. In our study no significant effect was seen on p21WAF1 expression by the combination of ciprofloxacin and etoposide but there was down-regulation of p21WAF1 gene by ciprofloxacin alone. Ciprofloxacin also inhibited NF-kappaB binding to DNA. Further studies in this area are warranted as the roles of p21WAF1, Bax/Bcl-2 and NF-kappaB may be important molecular events in mediating the antiproliferative and apoptosis inducing effect of etoposide in combination with ciprofloxacin in HRPC cells.
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July 2002