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author:("Ahmad, actab")
1.  Tissue Factor Signals Airway Epithelial Basal Cell Survival via Coagulation and Protease-Activated Receptor Isoforms 1 and 2 
Tissue factor (TF) initiates the extrinsic coagulation cascade and is a high-affinity receptor for coagulation factor VII. TF also participates in protease-activated receptor (PAR)1 and PAR2 activation. Human epithelial basal cells were previously purified on the basis of TF expression. The purpose of this study was to determine if tracheobronchial epithelial basal cell–associated TF drives coagulation and/or activates PARs to promote basal cell functions. We used human tracheobronchial tissues to isolate human airway epithelial cells using specific cell surface markers by flow cytometry and studied TF expression by immunostaining. TF-dependent fibrin network formation was observed by confocal and scanning electron microscopy. TF knockdown was done using short hairpin RNA, and TF mRNA was measured using quantitative RT-PCR. We found that 97 ± 5% of first-passage human tracheobronchial epithelial cells were basal cells, and 100% of these basal cells expressed TF. Basal cell–associated TF was active, but TF activity was dependent on added extrinsic coagulation cascade factors. TF inhibition caused basal cell apoptosis and necrosis. This was due to two parallel but interdependent TF-regulated processes: failure to generate a basal cell–associated fibrin network and suboptimal PAR1 and PAR2 activity. The data indicate that membrane surface TF mediates airway epithelial basal cell attachment, which maintains cell survival and mitotic potential. The implications of these findings are discussed in the context of basal cell–associated TF activity in normal and injured tissues and of the potential for repair of airway epithelium in lung disease.
doi:10.1165/rcmb.2012-0189OC
PMCID: PMC3547080  PMID: 23065128
tissue factor; epithelium; clotting; fibrin; tracheobronchial
2.  Estimation of total phenolic content, in-vitro antioxidant and anti-inflammatory activity of flowers of Moringa oleifera 
Objective
To evaluate and compare the antioxidant potential and anti-inflammatory activity of ethanolic extract of flowers of Moringa oleifera (M. oleifera) grown in Oman.
Methods
Flowers of M. oleifera were collected in the month of December 2012 and identified by a botanist. Alcoholic extract of the dry pulverized flowers of M. oleifera were obtained by cold maceration method. The ethanolic flower extract was subjected to preliminary phytochemical screening as the reported methods. Folin-Ciocalteu reagent was used to estimate total phenolic content. DPPH was used to determine in-vitro antioxidant activity and anti-inflammatory activity of flowers was investigated by protein denaturation method.
Results
Phytochemical analysis of extract showed presence of major classes of phytochemicals such as tannins, alkaloids, flavonoids, cardiac glycosides etc. M. oleifera flowers were found to contain 19.31 mg/g of gallic acid equivalent of total phenolics in dry extract but exhibited moderate antioxidant activity. The anti-inflammatory activity of plant extract was significant and comparable with the standard drug diclofenac sodium.
Conclusions
The results of our study suggest that flowers of M. oleifera possess potent anti-inflammatory activity and are also a good source of natural antioxidants. Further study is needed to identify the chemical compounds responsible for their anti-inflammatory activity.
doi:10.1016/S2221-1691(13)60126-4
PMCID: PMC3703555  PMID: 23905019
Antioxidant; Anti-inflammatory activity; DPPH; Total phenolic content
3.  Interaction and Localization of Synthetic Nanoparticles in Healthy and Cystic Fibrosis Airway Epithelial Cells: Effect of Ozone Exposure 
Abstract
Background
Nanoparticles (NPs) produced by nanotechnology processes have taken the field of medicine by storm. Concerns about safety of these NPs in humans, however, have recently been raised. Although studies of NP toxicity have focused on lung disease the mechanistic link between NP exposure and lung injury remained unclear. This is primarily due to a lack of availability of appropriate airway disease models and sophisticated microscopic techniques to study nano-sized particulate delivery and resulting responses.
Methods
Air–liquid interface (ALI) cultures of non-cystic fibrosis (CF) and CF airway epithelial cells were exposed to the FITC-labeled NPs using a PennCentury microsprayer™. Uptake of NPs was assessed by FACS. Laser scanning microscopy (LSM) was performed and the images were analyzed by an advanced imaging software to study particle deposition and uptake.
Results
Flow cytometry data revealed that CF cells accumulated increased amounts of NPs. The increased NP uptake could be attributed to the reduced CF transmembrane conductance regulator (CFTR) function as a similar increased retention/uptake was observed in cells whose CFTR expression was downregulated by antisense oligonucleotide. NPs alone did not induce pro-inflammatory cytokine release or cell death. The cell culture system was sensitive to ozone but exposure to the uncoated synthetic NPs used in this study, did not cause any synergistic or suppressive effects. LSM imaging and subsequent image restoration further indicated particle uptake and intracellular localization. Exposure to ozone increased nuclear uptake in both non-CF and CF cells.
Conclusion
Our findings demonstrate the uptake of NPs using ALI cultures of non-CF and CF airway epithelial cells. The NPs used here were useful in demonstrating uptake by airway epithelial cells without causing adverse effects in presence or absence of ozone. However, to totally exclude toxic effects, chronic studies under in vivo conditions using coated particulates are required.
doi:10.1089/jamp.2011.0889
PMCID: PMC3311910  PMID: 22007674
aerosol distribution; modeling; toxicology
4.  Hypoxia-Inducible Factor Regulates Expression of Surfactant Protein in Alveolar Type II Cells In Vitro 
Alveolar type II (ATII) cells cultured at an air–liquid (A/L) interface maintain differentiation, but they lose these properties when they are submerged. Others showed that an oxygen tension gradient develops in the culture medium as ATII cells consume oxygen. Therefore, we wondered whether hypoxia inducible factor (HIF) signaling could explain differences in the phenotypes of ATII cells cultured under A/L interface or submerged conditions. ATII cells were isolated from male Sprague-Dawley rats and cultured on inserts coated with a mixture of rat-tail collagen and Matrigel, in medium including 5% rat serum and 10 ng/ml keratinocyte growth factor, with their apical surfaces either exposed to air or submerged. The A/L interface condition maintained the expression of surfactant proteins, whereas that expression was down-regulated under the submerged condition, and the effect was rapid and reversible. Under submerged conditions, there was an increase in HIF1α and HIF2α in nuclear extracts, mRNA levels of HIF inducible genes, vascular endothelial growth factor, glucose transporter–1 (GLUT1), and the protein level of pyruvate dehydrogenase kinase isozyme–1. The expression of surfactant proteins was suppressed and GLUT1 mRNA levels were induced when cells were cultured with 1 mM dimethyloxalyl glycine. The expression of surfactant proteins was restored under submerged conditions with supplemented 60% oxygen. HIF signaling and oxygen tension at the surface of cells appears to be important in regulating the phenotype of rat ATII cells.
doi:10.1165/rcmb.2011-0052OC
PMCID: PMC3262688  PMID: 21454802
HIF; ATII cells; surfactant proteins; VEGF; GLUT1
5.  Prevalence of Myrsidea salimalii (Amblycera: Phthiraptera) on striated babblers (Turdoides earlei) (Timaliidae: Passeriformes: Aves) 
Survey of literature showed that the population characteristics of the phthirapterans parasitizing striated babblers deserved investigation. Hence, 30 birds were examined during 2007–2009 in district Rampur U.P. The prevalence of an amblyceran louse, Myrsidea salimalii on striated babblers was 40%. The mean intensity of infestation and the sample mean abundance were 33.5 and 13.4, respectively. The variance to mean ratio of the population exceeded unity (36.24). The frequency distribution pattern of the louse was aggregated but did not conform to the negative binomial model. Females outnumbered the males in natural condition (M:F—1:1.4) while the nymphal population had an edge over adult population (A:N—1:1.3).
doi:10.1007/s12639-011-0062-3
PMCID: PMC3235380  PMID: 23024506
Phthiraptera; Lice; Amblycera; Prevalence; Myrsidea
6.  SERCA2 Regulates Non-CF and CF Airway Epithelial Cell Response to Ozone 
PLoS ONE  2011;6(11):e27451.
Calcium mobilization can regulate a wide range of essential functions of respiratory epithelium, including ion transport, ciliary beat frequency, and secretion of mucus, all of which are modified in cystic fibrosis (CF). SERCA2, an important controller of calcium signaling, is deficient in CF epithelium. We conducted this study to determine whether SERCA2 deficiency can modulate airway epithelial responses to environmental oxidants such as ozone. This could contribute to the pathogenesis of pulmonary exacerbations, which are important and frequent clinical events in CF. To address this, we used air-liquid interface (ALI) cultures of non-CF and CF cell lines, as well as differentiated cultures of cells derived from non-CF and CF patients. We found that ozone exposure caused enhanced membrane damage, mitochondrial dysfunction and apoptotic cell death in CF airway epithelial cell lines relative to non-CF. Ozone exposure caused increased proinflammatory cytokine production in CF airway epithelial cell lines. Elevated proinflammatory cytokine production also was observed in shRNA-mediated SERCA2 knockdown cells. Overexpression of SERCA2 reversed ozone-induced proinflammatory cytokine production. Ozone-induced proinflammatory cytokine production was NF-κB- dependent. In a stable NF-κB reporter cell line, SERCA2 inhibition and knockdown both upregulated cytomix-induced NF-κB activity, indicating importance of SERCA2 in modulating NF-κB activity. In this system, increased NF-κB activity was also accompanied by increased IL-8 production. Ozone also induced NF-κB activity and IL-8 release, an effect that was greater in SERCA2-silenced NF-κB-reporter cells. SERCA2 overexpression reversed cytomix-induced increased IL-8 release and total nuclear p65 in CFTR-deficient (16HBE-AS) cells. These studies suggest that SERCA2 is an important regulator of the proinflammatory response of airway epithelial cells and could be a potential therapeutic target.
doi:10.1371/journal.pone.0027451
PMCID: PMC3214057  PMID: 22096575
7.  Cardiorenal syndromes 
Cardiorenal syndromes (CRS) have been subclassified as five defined entities which represent clinical circumstances in which both the heart and the kidney are involved in a bidirectional injury and dysfunction via a final common pathway of cell-to-cell death and accelerated apoptosis mediated by oxidative stress. Types 1 and 2 involve acute and chronic cardiovascular disease (CVD) scenarios leading to acute kidney injury or accelerated chronic kidney disease. Types 2 and 3 describe acute and chronic kidney disease leading primarily to heart failure, although it is possible that acute coronary syndromes, stroke, and arrhythmias could be CVD outcomes in these forms of CRS. Finally, CRS type 5 describes a simultaneous insult to both heart and kidneys, such as sepsis, where both organs are injured simultaneously. Both blood and urine biomarkers are reviewed in this paper and offer a considerable opportunity to enhance the understanding of the pathophysiology and known epidemiology of these recently defined syndromes.
doi:10.4330/wjc.v3.i1.1
PMCID: PMC3030731  PMID: 21286212
Heart diseases; Kidney diseases; Cardiovascular diseases; Biological biomarkers; Creatinine
8.  Bio-Ecology of the Louse, Upupicola upupae, Infesting the Common Hoopoe, Upupa epops  
The population characteristics of the louse, Upupicola upupae (Shrank) (Mallophaga: Philopteridae: Ishnocera), infesting the Common Hoopae, Upupa epops L. (Aves: Upupiformes), were recorded during 2007–08 in District Rampur, Uttar Pradesh India. The pattern of frequency distribution of the louse conformed to the negative binomial model. The lice and its nits were reared in vitro at 35 ± 1° C, 75–82 % RH, on a feather diet. The data obtained was used to construct the life table and to determine the intrinsic rate of natural increase (0.035 female/day), the net reproductive rate was 3.67 female eggs/female, the generation time was 37 days, and the doubling time of the population was 19 days. The chaetotaxy of the three nymphal instars has also been noted to record their diagnostic characteristics. Information on egg morphology and antennal sensilla is also presented.
doi:10.1673/031.011.4601
PMCID: PMC3281440  PMID: 21861650
Ischnocera; Phthiraptera; Upupicola upupae
9.  Bcl-2 Suppresses Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase Expression in Cystic Fibrosis Airways 
Rationale: Modulation of the activity of sarcoendoplasmic reticulum calcium ATPase (SERCA) can profoundly affect Ca2+ homeostasis. Although altered calcium homeostasis is a characteristic of cystic fibrosis (CF), the role of SERCA is unknown.
Objectives: This study provides a comprehensive investigation of expression and activity of SERCA in CF airway epithelium. A detailed study of the mechanisms underlying SERCA changes and its consequences was also undertaken.
Methods: Lung tissue samples (bronchus and bronchiole) from subjects with and without CF were evaluated by immunohistochemistry. Protein and mRNA expression in primary non-CF and CF cells was determined by Western and Northern blots.
Measurements and Main Results: SERCA2 expression was decreased in bronchial and bronchiolar epithelia of subjects with CF. SERCA2 expression in lysates of polarized tracheobronchial epithelial cells from subjects with CF was decreased by 67% as compared with those from subjects without CF. Several non-CF and CF airway epithelial cell lines were also probed. SERCA2 expression and activity were consistently decreased in CF cell lines. Adenoviral expression of mutant F508 cystic fibrosis transmembrane regulator gene (CFTR), inhibition of CFTR function pharmacologically (CFTRinh172), or stable expression of antisense oligonucleotides to inhibit CFTR expression caused decreased SERCA2 expression. In CF cells, SERCA2 interacted with Bcl-2, leading to its displacement from caveolae-related domains of endoplasmic reticulum membranes, as demonstrated in sucrose density gradient centrifugation and immunoprecipitation studies. Knockdown of SERCA2 using siRNA enhanced epithelial cell death due to ozone, hydrogen peroxide, and TNF-α.
Conclusions: Reduced SERCA2 expression may alter calcium signaling and apoptosis in CF. These findings decrease the likelihood of therapeutic benefit of SERCA inhibition in CF.
doi:10.1164/rccm.200807-1104OC
PMCID: PMC2675566  PMID: 19201925
cystic fibrosis; SERCA2; pulmonary epithelium; ER
10.  Khamiras, a natural cardiac tonic: An overview 
The Unani system of Medicine (Unanipathy), which originated in Greece, is based on the principles proposed by Galen, a Greek practitioner. Since then, many Arab and Persian scholars have contributed to the system. Among them Ibn-e-Sina, an Arab philosopher and Physicist who wrote ‘Kitab-al-shifa’ are worth mentioning. This system has an extensive and inspiring record in India. It was introduced in India around the tenth century A.D with the spread of Islamic civilization. At present, Unanipathy has become an important part of the Indian system of Medicine. Unani medicines have been used since ancient times, as medicines for the treatment of various ailments. In spite of the great advances observed in modern medicine in recent decades, Unani drugs still make an important contribution to healthcare. The Unani system of medicine is matchless in treating chronic diseases like arthritis, asthma, mental, cardiac, and digestive disorders, urinary infections, and sexual diseases. The medicines administered go well with the temperament of the patient, thus speeding up the process of recovery and also reducing the risk of drug reaction. The Unani system of medicine recognizes the influence of the surroundings and ecological conditions on the state of health of human beings. The system aims at restoring the equilibrium of various elements and faculties of the human body. It has laid down six essential prerequisites for the prevention of diseases and places great emphasis, on the one hand, on the maintenance of proper ecological balance, and on the other, on keeping water, food, and air free from pollution. These essentials, known as ‘Asbab-e-Sitta Zarooriya’, are air, food, and drink, bodily movement and repose, psychic movement and repose, sleep and wakefulness, and excretion and retention. The Unani system is a secular system in temperament and is popular among the masses. In Unani medicine, although the general preference is for single drugs, compound formulations are also used in the treatment of various complex and chronic disorders. In the light of the present knowledge, this review is a small effort to discuss the efficacious nature of ‘Khamira’, a semi-solid preparation, which is traditionally used for cardiac ailments, such as, palpitations, weakness of the heart, and so on. On the basis of their constituents these are named as, Khamira Aabresham, Khamira Gaozaban, Khamira Marwareed, and so on. Khameeras are also used as general tonics for other vital organs like the liver and brain. In view of the increasing number of cardiac diseases, a thorough evaluation of this ancient work on Khamira is of special significance.
doi:10.4103/0975-7406.67009
PMCID: PMC3147110  PMID: 21814439
Cardiotonic; khameera; Unani system of medicine
11.  Population Characteristics and the Nature of Egg Shells of two Phthirapteran Species Parasitizing Indian Cattle Egrets 
The prevalence, intensities of infestation, range of infestation and population composition of two phthirapteran species, Ardeicola expallidus Blagoveshtchensky (Phthiraptera: Philopteridae) and Ciconiphilus decimfasciatus Boisduval and Lacordaire (Menoponidae) on seventy cattle egrets were recorded during August 2004 to March 2005, in India. The frequency distribution patterns of both the species were skewed but did not correspond to the negative binomial model. The oviposition sites, egg laying patterns and the nature of the eggs of the two species were markedly different.
doi:10.1673/031.010.14123
PMCID: PMC3016757  PMID: 21067416
Amblycera; lschnocera; Ardeicola expallidus; Ciconiphilus decimfasciatus
12.  Pulmonary Embolectomy 
Western Journal of Medicine  1978;128(5):377-381.
Embolectomy was carried out in eight patients with pulmonary emboli. Angiographic diagnosis was obtained in six, and in two cases pulmonary angiography could not be done because of the very critical condition of the patients. In the latter two, diagnosis was made based only on clinical findings. Two patients died in the operating room (25 percent). Six patients were discharged in good condition.
It is emphasized that pulmonary embolectomy should be done in cases of pulmonary emboli when a clinical status of shock is present (systolic blood pressure less than 80 mm of mercury and the patient in low cardiac output syndrome) and when there is no response to medical treatment regardless of the degree of obstruction in the pulmonary arterial tree.
Images
PMCID: PMC1238147  PMID: 664640

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