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Ibuprofen is widely used as a prescription and non-prescription medicine. The aim of study is to prepare Ibuprofen tablets (200mg) using direct compression technique which is now days considered a cost effective and simple method of manufacturing. It is considered as an appropriate method for hygroscopic and thermolabile substances. In order to obtain the best, optimized product, nine different formulations were developed. Diluent (X1), disintegrant (X2) and lubricant (X3) were taken as independent variables. Weight variation (Y1), thickness (Y2), length and width (Y3), hardness (Y4), friability (Y5), disintegration (Y6), dissolution (Y7) and pharmaceutical assay (Y8) were studied as response variables. The results of all nine formulations were found within the acceptable limits conforming to those given in official compendia. However, F-6 was selected as an optimized product on the basis of high dissolution (99.05%) and Assay (100.04%). The variation of weight among the tablets of F-6 was least which showed best ratio of excipients in the formulation. Optimization has proven as an effective tool in product development. This is because no clear relationship exists between the variables.

Many tumour cells have elevated rates of glucose uptake but reduced rates of oxidative phosphorylation. This persistence of high lactate production by tumours in the presence of oxygen, known as aerobic glycolysis, was first noted by Otto Warburg more than 75 yr ago. How tumour cells establish this altered metabolic phenotype and whether it is essential for tumorigenesis is as yet unknown. Here we show that a single switch in a splice isoform of the glycolytic enzyme pyruvate kinase is necessary for the shift in cellular metabolism to aerobic glycolysis and that this promotes tumorigenesis. Tumour cells have been shown to express exclusively the embryonic M2 isoform of pyruvate kinase. Here we use short hairpin RNA to knockdown pyruvate kinase M2 expression in human cancer cell lines and replace it with pyruvate kinase M1. Switching pyruvate kinase expression to the M1 (adult) isoform leads to reversal of the Warburg effect, as judged by reduced lactate production and increased oxygen consumption, and this correlates with a reduced ability to form tumours in nude mouse xenografts. These results demonstrate that M2 expression is necessary for aerobic glycolysis and that this metabolic phenotype provides a selective growth advantage for tumour cells in vivo.

MicroRNAs are abundant in animal genomes and have been predicted to have important roles in a broad range of gene expression programmes. Despite this prominence, there is a dearth of functional knowledge regarding individual mammalian microRNAs. Using a loss-of-function allele in mice, we report here that the myeloid-specific microRNA-223 (miR-223) negatively regulates progenitor proliferation and granulocyte differentiation and activation. miR-223 (also called Mirn223) mutant mice have an expanded granulocytic compartment resulting from a cell-autonomous increase in the number of granulocyte progenitors. We show that Mef2c, a transcription factor that promotes myeloid progenitor proliferation, is a target of miR-223, and that genetic ablation of Mef2c suppresses progenitor expansion and corrects the neutrophilic phenotype in miR-223 null mice. In addition, granulocytes lacking miR-223 are hypermature, hypersensitive to activating stimuli and display increased fungicidal activity. As a consequence of this neutrophil hyperactivity, miR-223 mutant mice spontaneously develop inflammatory lung pathology and exhibit exaggerated tissue destruction after endotoxin challenge. Our data support a model in which miR-223 acts as a fine-tuner of granulocyte production and the inflammatory response.

Chimerism in humans is a rare phenomenon often initially identified in the resolution of an ABO blood type discrepancy. We report a dispermic chimera who presented with mixed field in his B antigen typing that might have been mistaken for the B3 subtype. The propositus is a healthy Korean male blood donor. Neither his clinical history nor initial molecular investigation of his ABO gene explained his mixed field agglutination with murine anti-B. Chimerism was suspected, and 9 short tandem repeat (STR) loci were analyzed on DNA extracted from blood, buccal swabs, and hair from this donor and on DNA isolated from peripheral blood lymphocytes from his parents. The propositus' red blood cells demonstrated mixed field agglutination with anti-B. Exon 6 and 7 and flanking intronic regions of his ABO gene were sequenced and revealed an O01/O02 genotype. B allele haplotype-specific PCR, along with exon 6 and 7 cloning and sequencing demonstrated a third ABO allele, B101. Four STR loci demonstrated a pattern consistent with a double paternal chromosome contribution in the propositus, thus confirming chimerism. His karyotype revealed a mosaic pattern: 32/50 metaphases were 46,XY and 18/50 metaphases demonstrated 47,XYY.

Circa 2001, Aunt Abby had reached her seventh decade when she was diagnosed with advanced ovarian cancer. Chances of cure were slim to nil, and true to her Midwestern upbringing and staunch faith that a better world awaits, Aunt Abby chose to live out her last months at home, "doing" for Uncle Bill, as she had for the last fifty-two years. Uncle Bill and the kids understood and were willing to abide by her wishes to just let her pass, as God would will. But, when the day came that Aunt Abby's heart failed, she was puttering through the local grocery alone, while Uncle Bill slipped around the corner to pick up parts from the hardware store. An alert store clerk called 911. The EMS team arrived quickly, and, as their protocol required, began resuscitation. Aunt Abby's wish for a death with "no fuss" was no match for the emergency medical system's clinical and legal duty to treat until a physician ordered otherwise.

Spirituality is essential to healthcare. It is that part of human beings that seeks meaning and purpose in life. Spirituality in the clinical setting can be manifested as spiritual distress or as resources of strength. Patients' spiritual beliefs can impact diagnosis and treatment. Spiritual care involves an intrinsic aspect of care, which underlies compassionate and altruistic caregiving and is an important element of professionalism amongst the various healthcare professionals. It also involves an extrinsic element, which includes spiritual history, assessment of spiritual issues, as well as resources of strength and incorporation of patients' spiritual beliefs and practices into the treatment or care plan. Spiritual care is interdisciplinary care-each member of the interdisciplinary team has responsibilities to provide spiritual care. The chaplain is the trained spiritual care expert on the team. Optimally, all healthcare professionals, including the chaplain, on the team interact with each other to develop and implement the spiritual care plan for the patient in a fully collaborative model.

The aim of this study is to develop a once-daily sustained release matrix tablet of ibuprofen using hydroxypropyl methylcellulose (HPMC) as release controlling factor and to evaluate drug release parameters as per various release kinetic models. In order to achieve required sustained release profile tablets were directly compressed using Avicel pH 101 and Magnesium stearate. The formulated tablets were also characterized by physical and chemical parameters and results were found in acceptable limits. Different dissolution models were applied to drug release data in order to evaluate release mechanisms and kinetics. Criteria for selecting the most appropriate model was based on linearity (coefficient of correlation). The drug release data fit well to the Higuchi expression. Drug release mechanism was found as a complex mixture of diffusion, swelling and erosion.

Researchers have extended the literature on strategies of gaining compliance with a request to incorporate cultural variations into the analytic framework. In the present investigation, the authors sought to go beyond previous studies of the factors increasing compliance rates by reexamining how researchers conceptualize and measure personal, social, and cultural influences on compliance behavior in the United States, Poland, and Hong Kong. The authors found that different levels of compliance were affected by culture, principles of influence, and the individual's personal orientation of idiocentrism/allocentrism (I/A). In the present study, the authors extended previous cross-cultural work by decomposing the I/A into 2 separate individual difference variables: normative perceptions and evaluative perceptions. The interaction of person and situation on compliance showed the power of situational demands and the strength of different aspects of personal collectivism. Different patterns of compliance at the culture level revealed the importance of culture in shaping this behavioral tendency. Thus, the authors' integration of personal, social, and cultural influences provided an interactive model to help researchers explain compliance more comprehensively.

Death ideation and death anxiety represent the cognitive and affective dimensions of death attitudes, respectively. General beliefs about the world are proposed to be useful defensive mechanisms protecting persons against the death anxiety provoked by death ideation. SEM is employed to test the proposed mediation model, using a sample of 133 Hong Kong Chinese university students. Results showed that death ideation was significantly and inversely linked to belief in social cynicism, reward for application, and fate control. Moreover, higher levels of belief in fate control and lower levels of religiosity predicted greater death anxiety. Only belief in fate control partially mediated the relationship between death ideation and death anxiety. Discussion focused on how social axioms serve as useful defensive mechanisms against death anxiety.

Suicide is usually conceptualized as arising either because of social phenomena or individual dynamics. In this study, these approaches were combined by analyzing suicide rates of younger people aged 15-24 and elderly aged 65-74 from 54 nations using societal variables in conjunction with psychological measures of citizen characteristics as mediators. A mediated analysis showed that psychological citizen factors, like home satisfaction and happiness, mediated the impact of societal variables, like the sex ratio, in predicting suicide rates. We found different psychological and societal predictors for young and elderly suicides, with elderly suicide rates being much more predictable. An age-responsive Durkheimian framework focusing on the dynamics of social integration at different ages was used to interpret these results.

Antibacterial activity of 1-methyl-7-methoxy-beta-carboline (harmaline) and its phenacyl and coumarine analogues 1-(3-nitro-phenyl)-(2-(7-methoxy-1-methyl-1,3,4,9-tetrahydro-beta-carbolin-2-yl)-ethanone (II), 1-(3,4-dihydroxy-phenyl)-2-(7-methoxy-1-methyl-1,3,4,9-tetrahydro-beta-carbolin-2-yl)-ethanone (III) 7-(methoxy-beta-carboline),15-24,de-hydro(19,20-dimethoxy)coumarine (IV), 7-(methoxy-beta-carboline)15-24,dehydro(20-methoxy)coumarine (V) were studied by disc diffusion method. All compounds were tested against three gram positive and four gram-negative bacteria. Parent compound showed good activity. All compounds revealed better results against gram positive as compared to gram-negative bacteria. 1-(3,4-Dihydroxy-phenyl)-2-(7-methoxy-1-methyl-1,3,4,9-tetrahydro-beta-carbolin-2-yl)-ethanone (III) was found most potent compound showing broad spectrum activity when compared with all synthesized analogues. Coumarine analogues showed more or less same activity indicating that number and position of methoxy groups are not important regarding antimicrobial activity.

In animals, cells are dependent on extracellular signals to prevent apoptosis. However, using growth factor-dependent cells from Bax/Bak-deficient mice, we demonstrate that apoptosis is not essential to limit cell autonomous survival. Following growth factor withdrawal, Bax-/-Bak-/- cells activate autophagy, undergo progressive atrophy, and ultimately succumb to death. These effects result from loss of the ability to take up sufficient nutrients to maintain cellular bioenergetics. Despite abundant extracellular nutrients, growth factor-deprived cells maintain ATP production from catabolism of intracellular substrates through autophagy. Autophagy is essential for maintaining cell survival following growth factor withdrawal and can sustain viability for several weeks. During this time, cells respond to growth factor readdition by rapid restoration of the ability to take up and metabolize glucose and by subsequent recovery of their original size and proliferative potential. Thus, growth factor signal transduction is required to direct the utilization of sufficient exogenous nutrients to maintain cell viability.

Tablets are the most common dosage form. Tablets can be prepared by dry method and wet methods, both methods have their own significance as well as disadvantages. Dry method and particularly direct compression is most simplest method of tablet manufacturing. On the other hand granulation is a multiple processing method which add complexity and make validation and control difficult. For comparative study of atenolol tablets a new formulation was designed and compressed by direct compression method. Then it's physical parameters including hardness, friability, diameter, thickness, disintegration time, dissolution test were performed and finally assay carried out for evaluation and characterization of this new formulation against other formulation available in the market.

The relationship between growth factor-dependent cell growth and proliferation and the up-regulation of cellular metabolism required to support these processes remains poorly defined. Here, we demonstrate that cell growth, proliferation, and glucose metabolism are coordinately regulated by interleukin-3 (IL-3) in cytokine-dependent cells. Surprisingly, glycolytic activity is stimulated to a greater extent than would be expected based on the rate of cell growth or proliferation. IL-3 signaling exerts a direct effect on glycolytic commitment independent of cell growth control. These results are not restricted to IL-3 as the cytokines IL-7 and IL-2 have similar effects on glucose metabolism when assayed in factor-dependent cell lines or primary lymphocytes, respectively. Growth factor stimulation leads cells to consume less oxygen and produce more lactate per glucose, indicative of conversion from oxidative to glycolytic metabolism. The enforced rate of glucose metabolism is in excess of that required to support cell growth; accordingly, if extracellular glucose is reduced, cells retain the ability to grow and proliferate by derepressing oxidative metabolism. These data suggest that the high rate of glycolysis observed in response to growth factor stimulation is a primary effect rather than a homeostatic response to increased cell growth.

Cancer cells frequently display high rates of aerobic glycolysis in comparison to their nontransformed counterparts, although the molecular basis of this phenomenon remains poorly understood. Constitutive activity of the serine/threonine kinase Akt is a common perturbation observed in malignant cells. Surprisingly, although Akt activity is sufficient to promote leukemogenesis in nontransformed hematopoietic precursors and maintenance of Akt activity was required for rapid disease progression, the expression of activated Akt did not increase the proliferation of the premalignant or malignant cells in culture. However, Akt stimulated glucose consumption in transformed cells without affecting the rate of oxidative phosphorylation. High rates of aerobic glycolysis were also identified in human glioblastoma cells possessing but not those lacking constitutive Akt activity. Akt-expressing cells were more susceptible than control cells to death after glucose withdrawal. These data suggest that activation of the Akt oncogene is sufficient to stimulate the switch to aerobic glycolysis characteristic of cancer cells and that Akt activity renders cancer cells dependent on aerobic glycolysis for continued growth and survival.

This article is an attempt to study the neglected linkages between culture and aggression. It does so by conceptualizing culture as a set of affordances and constraints that channel the expression of coercive means of social control by self and others. All cultural systems represent solutions to the problems associated with distributing desired material and social resources among its group members while maintaining social order and harmony. Norms are developed surrounding the exercise of mutual influence in the process of resource allocation, favoring some and marginalizing others. Violations of these norms by resource competitors are conceptualized as "aggressive" behaviors and stimulate a process of justified counter attack, escalating the violence. The current data from both societal-level and individual-level studies are examined and integrated in light of this organizing framework, and future studies are proposed to explore the interface between culture and aggression more productively.

The proapoptotic Bcl-2 family members Bak and Bax play central and redundant roles in the regulation of apoptosis. In this study, we investigated the effect of loss of Bax and Bak in the CNS. The adult bax-/-bak-/- mice display masses of densely staining cells in the proliferative zones of the brain. These cells are shown to be a mix of neural progenitor cells and postmitotic cells at different stages of neural and glial differentiation. Both neural progenitor cells and mature neurons derived from bax-/-bak-/- mice were resistant to various apoptotic stimuli. Despite this resistance, postmitotic mature bax-/-bak-/- neurons remain as sensitive to excitoxic death as wild-type neurons. Thus, Bax and Bak play a critical role in regulating the number of neural progenitor cells in the adult brain but are not absolutely required for the initiation of neuronal cell death after neurotoxic injury.

During apoptosis, the mitochondrial membrane potential (MMP) decreases, but it is not known how this relates to the apoptotic process. It was recently suggested that cytochrome c is compartmentalized in closed cristal regions and therefore, matrix remodeling is required to attain complete cytochrome c release from the mitochondria. In this work we show that, at the onset of apoptosis, changes in MMP control matrix remodeling prior to cytochrome c release. Early after growth factor withdrawal the MMP declines and the matrix condenses. Both phenomena are reversed by adding oxidizable substrates. In mitochondria isolated from healthy cells, matrix condensation can be induced by either denying oxidizable substrates or by protonophores that dissipate the membrane potential. Matrix remodeling to the condensed state results in cristal unfolding and exposes cytochrome c to the intermembrane space facilitating its release from the mitochondria during apoptosis. In contrast, when a transmembrane potential is generated due to either electron transport or a pH gradient formed by acidifying the medium, mitochondria maintain an orthodox configuration in which most cytochrome c is sequestered in the cristae and is resistant to release by agents that disrupt the mitochondrial outer membrane.

All eukaryotic organisms have mechanisms to adapt to changing metabolic conditions. The mammalian cell survival gene Bcl-x(L) enables cells to adapt to changes in cellular metabolism. To identify genes whose function can be substituted by Bcl-x(L) in a unicellular eukaryote, a genetic screen was performed using the yeast Saccharomyces cerevisiae. S. cerevisiae grows by anaerobic glycolysis when glucose is available, switching to oxidative phosphorylation when carbohydrate in the media becomes limiting (diauxic shift). Given that Bcl-x(L) appears to facilitate the switch from glycolytic to oxidative metabolism in mammalian cells, a library of yeast mutants was tested for the ability to efficiently undergo diauxic shift in the presence and absence of Bcl-x(L). Several mutants were identified that have a defect in growth when switched from a fermentable to a nonfermentable carbon source that is corrected by the expression of Bcl-x(L). These genes include the mitochondrial chaperonin TCM62, as well as previously uncharacterized genes. One of these uncharacterized genes, SVF1, promotes cell survival in mammalian cells in response to multiple apoptotic stimuli. The finding that TCM62 and the analogous human prohibitin gene also inhibit mammalian cell death following growth factor withdrawal implicates mitochondrial chaperones as regulators of apoptosis. Further characterization of the genes identified in this screen may enhance our understanding of Bcl-x(L) function in mammalian cells, and of cell survival pathways in general.

Microbial resistance to majority of the available antimicrobial agent is a serious and global problem. Due to heavy and discriminate usage of antibiotics, high prevalence of drug-resistant bacteria in the indigenous fecal flora, poor standards of sanitation, lack of education and prevalence of malnutrition. This problem is at its extreme in developing countries like Pakistan. For this various Aminoglycosides were tested against different Gram positive and Gram negative isolates. The results showed that these isolates were resistant against most of these antibiotics with increase in MIC's. In Aminoglycoside group Tobramycin was the most effective agent against Staph. aureus and E. coli with MIC90s of 1 microg/ml and 2 microg/ml, while against Klebsiella and P. aeruginosa its activity was moderate to low. Amikacin showed highest activity against P. aeruginosa, E. coli and Klebsiella species with MIC90s of 4 microg/ml and 8 microg/ml. Kanamycin and Streptomycin were not active against the tested isolates.

More than 90% of world's children are born each year in the developing world. Each year 12.9 million children die. Twenty eight percent of death are caused by pneumonia, 23% by diarrheal disease and 16% by vaccine-preventable diseases. Thirty-five thousand die each day, most from common and preventable problems. Health and illness are the result of a complex dynamic of environmental, social, political and economic factors. Bacterial resistance to antimicrobial agents is a continuing serious problem in the treatment of infections. Although this problem was recognized shortly after the commercial introduction of antimicrobial agents, it means that resistance is now emerging at a more rapid rate than ever before. To start with, during the present study an effort has been made to accomplish this task, 84 clinical isolates of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa were collected from different hospitals in Karachi. An in vitro study of these isolates was carried out by Agar dilution method using eleven antimicrobial agents and their combination (Lorian, 1991). Among Cephalosporins, third generation Cephalosporin, Cefotaxime was highly effective against Gram positive and Gram negative bacteria. Cefotaxime was active against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. 1.19% isolates of Staphylococcus aureus, 19% isolates of Escherichia coli and 10% isolates of Pseudomonas aeruginosa were resistant against Cefotaxime. In Quinolone group, Ofloxacin was highly active against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Whereas 28% isolates of Staphylococcus aureus, 26% isolates of Escherichia coli and 11% isolates of Pseudomonas aeruginosa were resistant to Ofloxacin. Twenty six percent isolates of Staphylococcus aureus and 58% isolates Escherichia coli were resistant against Ciprofloxacin.