Formulation and Evaluation of Tramadol HCl Matrix Tablets Using Carbopol 974P and 934 as Rate-Controlling Agents

Purpose: To formulate and prepare controlled release (CR) matrix tablets of tramadol HCl using Carbopol 974P and 934 polymers as rate-controlling agents.Methods: The tablets were prepared by direct compression method using various drug to polymer (D:P) ratios. Co-excipients, including carboxymethylcellulose, starch and/or hydroxypropyl methylcellulosewere also used to modulate the formulations. Various physical tests and in vitro dissolution studies were carried out on the formulations. The dissolution data were subjected to various release modelsResults: As the concentration of the polymer (rate-controlling agent) increased, dissolution rate decreased, For the formulation containing Carbopol 974P at D:P ratio of 10:7, drug release decreased to 83 % compared with the release rate of 99 % for the formulation with D:P ratio of 10:3. Kinetic analysis indicates that drug release mechanism was anomalous non-Fickian diffusion.Conclusion: Both Carbopol 974P and 934 can be used as rate-controlling agents in the formulation of tramadol HCl CR tablets. Appropriate selection of drug/polymer ratio can be applied effectively to modulate the dissolution rate of the drug.Keywords: Tramadol, Carbopol, Carboxymethylcellulose (CMC), Hydroxypropyl methylcellulose, Controlled releas

Influence of genotype and age of explant source on the capacity for somatic embryogenesis of two Cavendish banana cultivars (Musa acuminata Colla, AAA)

The embryogenic capacities of flower explants from one- and two-week-old male inflorescence buds from Musa acuminata Cavendish, AAA, genotypes ‘Williams’ and ‘Grand Naine’ were investigated. Explants of hands with immature flowers were excised and induced for embryogenesis. Highlysignificant differences were found in the embryogenic response, depending on the genotype and the developmental stage of the buds from which the explants were excised. After four months of induction, the total percentage of callus formed ranged from 97.81% in explants of two-week-old ‘Williams’ buds to 52.11% in explants of two-week-old ‘Grand Naine’ buds. Embryogenic callus formation was, on average, higher in the two-week-old ‘Williams’ explants (10.01%) than in the one-week-old explants (0.78%). The opposite was true for ‘Grand Naine’, with 7.51% embryogenic callus produced in explants of one-week-old buds compared to 2.49% in two-week-old buds. Selected embryogenic calluses that were successfully established on proliferation medium led to embryogenic cell suspensions with good regeneration capacities. Fifteen to thirty-five percent of the embryos germinated, demonstrated high plant-conversion capacity (99%). The effect of the interaction between the developmental age ofexplant and the genotype on the embryogenesis response is discussed

Evidence for an increase in cosmogenic 10Be during a geomagnetic reversal

Reversals in the geomagnetic field, which occur every few hundred thousand years, represent a dramatic change in the Earth's environment. Although there is no satisfactory theory for such reversals, it is generally accepted that the dipole field intensity decreases to <20% of its 'normal' value for a few thousand years during the change in direction. Because the galactic and solar cosmic rays which impinge on the Earth's atmosphere are charged, a significant fraction (about half) of them are deflected by the geomagnetic field. At the time of a reversal, this magnetic shielding is greatly reduced, and it has been suggested that the increased flux of high-energy particles could have effects on evolutionary or climatic processes. For example, the statistically significant coincidence in levels of some marine faunal extinctions and reversal boundaries in ocean sediments could be caused, directly or indirectly, by the decreased geomagnetic intensity during the reversal. We report here evidence in marine sediments for an increase in cosmogenic 10Be production in the Earth's atmosphere during the Brunhes-Matuyama reversal 730,000 yr ago. In addition to confirming an increase in cosmogenic isotope production, the results provide information on the magnitude and duration of the geomagnetic intensity decrease during such an event, and the depth at which remanent magnetism is acquired in marine sediments

A RAC/CDC-42–Independent GIT/PIX/PAK Signaling Pathway Mediates Cell Migration in C. elegans

P21 activated kinase (PAK), PAK interacting exchange factor (PIX), and G protein coupled receptor kinase interactor (GIT) compose a highly conserved signaling module controlling cell migrations, immune system signaling, and the formation of the mammalian nervous system. Traditionally, this signaling module is thought to facilitate the function of RAC and CDC-42 GTPases by allowing for the recruitment of a GTPase effector (PAK), a GTPase activator (PIX), and a scaffolding protein (GIT) as a regulated signaling unit to specific subcellular locations. Instead, we report here that this signaling module functions independently of RAC/CDC-42 GTPases in vivo to control the cell shape and migration of the distal tip cells (DTCs) during morphogenesis of the Caenorhabditis elegans gonad. In addition, this RAC/CDC-42–independent PAK pathway functions in parallel to a classical GTPase/PAK pathway to control the guidance aspect of DTC migration. Among the C. elegans PAKs, only PAK-1 functions in the GIT/PIX/PAK pathway independently of RAC/CDC42 GTPases, while both PAK-1 and MAX-2 are redundantly utilized in the GTPase/PAK pathway. Both RAC/CDC42–dependent and –independent PAK pathways function with the integrin receptors, suggesting that signaling through integrins can control the morphology, movement, and guidance of DTC through discrete pathways. Collectively, our results define a new signaling capacity for the GIT/PIX/PAK module that is likely to be conserved in vertebrates and demonstrate that PAK family members, which are redundantly utilized as GTPase effectors, can act non-redundantly in pathways independent of these GTPases

Prophylactic HPV vaccines: prospects for eliminating ano-genital cancer

Virtually all cases of cervical cancer and its precursor intra-epithelial lesions are a result of infection with one or other of a subset of genital human papillomaviruses (HPVs), suggesting that prevention of HPV infection by prophylactic vaccination would be a highly effective anticancer strategy. Two HPV L1 virus-like particle vaccines have been developed, a quadrivalent HPV16/18/6/11 product and a bivalent HPV16/18 product; both have been shown to be highly immunogenic with a good safety profile and 100% efficacy against HPV16/18-related high-grade cervical intra-epithelial neoplasia (CIN2/3), implying that they will be effective at preventing HPV16/18-related cervical cancer

Keratin 8 expression in colon cancer associates with low faecal butyrate levels

<p>Abstract</p> <p>Background</p> <p>Butyrate has been implicated in the mechanistic basis of the prevention of colorectal cancer by dietary fibre. Numerous in vitro studies have shown that butyrate regulates cell cycle and cell death. More recently we have shown that butyrate also regulates the integrity of the intermediate filament (IF) cytoskeleton <it>in vitro</it>. These and other data suggest a link between the role of diet and the implication of a central role for the keratin 8 (K8) as guardian of the colorectal epithelium.</p> <p>Methods</p> <p>In this cross-sectional study possible links between butyrate levels, field effects and keratin expression in cancer were addressed directly by analysing how levels of expression of the IF protein K8 in tumours, in adjacent fields and at a distant landmark site may be affected by the level of butyrate in the colon microenvironment. An immunohistochemical scoring protocol for K8 was developed and applied to samples, findings were further tested by immunoblotting.</p> <p>Results</p> <p>Levels of K8 in colorectal tumours are lower in subjects with higher levels of faecal butyrate. Immunoblotting supported this finding.Although there were no significant relationships with butyrate on the non-tumour tissues, there was a consistent trend in all measures of extent or intensity of staining towards a reduction in expression with elevated butyrate, consistent with the inverse association in tumours.</p> <p>Conclusions</p> <p>The data suggest that butyrate may associate with down-regulation of the expression of K8 in the cancerized colon. If further validated these findings may suggest the chemopreventive value of butyrate is limited to early stage carcinogenesis as low K8 expression is associated with a poor prognosis.</p

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

Left ventricular volume: an optimal parameter to detect systolic dysfunction on prospectively triggered 64-multidetector row computed tomography: another step towards reducing radiation exposure

In this study, we define the correlation between LV volumes (both LV end-diastolic volume [LVEDV] and LV end-systolic volume [LVESV]) and ejection fraction (EF) on 64 slice multi-detector computed tomography (MDCT). We also determine the accuracy of all the LV volume (LVV) parameters to detect LV systolic dysfunction (LVSD) and investigate the feasibility of using LVV as a surrogate of LVSD on prospectively gated imaging to prevent the radiation exposure of retrospective imaging. 568 patients undergoing 64-detector MDCT were divided into 2 groups: Group 1—subjects without any heart disease and LVEF ≥ 50%; and Group 2—patients with coronary artery disease and LVEF < 50% (defined as LVSD). The LVV (LV cavity only) and Total LV volume (cavity + LV mass) at end-systole and end-diastole (LVESV, Total LVESV, LVEDV and Total LVEDV) were measured. The upper limit values (mean + 2 SD) of all LVV parameters in Group 1 were used as the reference criterion to diagnose LVSD in Group 2. An exponential correlation was found between LVEF and all the LVV parameters. The specificity to detect LVSD in Group 2 was >90% and the sensitivity was 88.9, 83.3, 61.3 and 74.9% by using LVESV, Total LVESV, LVEDV and Total LVEDV, respectively. Systolic and diastolic LV volumes had a high correlation with LVEF and a high accuracy to detect LVSD. Thus, on prospectively triggered imaging, ventricular volumes can predict patients with reduced LVEF, and appropriate referrals can be made

Female genital schistosomiasis as an evidence of a neglected cause for reproductive ill-health: a retrospective histopathological study from Tanzania

BACKGROUND: Schistosomiasis affects the reproductive health of women. Described sequelae are ectopic pregnancy, infertility, abortion, and cervical lesions and symptoms mimicking cervical cancer and STIs. There are indications that cervical schistosomiasis lesions could become co-factors for viral infection such as HIV and HPV. METHODS: In a retrospective descriptive histopathological study clinical specimens sent between 1999 and 2005 to the pathology department of a consultant hospital in Tanzania were reviewed to analyse the occurrence and features of schistosomiasis in female genital organs. RESULTS: During the study period, schistosomiasis was histopathologically diagnosed in 423 specimens from different organs (0.7% of all specimens examined in the study period), out of those 40% were specimens from female and male organs. The specimens were sent from 24 hospitals in 13 regions of mainland Tanzania. Female genital schistosomiasis was diagnosed in 125 specimens from 111 patients. The main symptoms reported were bleeding disorders (48%), ulcer (17%), tumor (20%), lower abdominal pain (11%) and infertility (7%). The majority of cases with genital schistosomiasis were diagnosed in cervical tissue (71 cases). The confirmation of cervical cancer was specifically requested for 53 women, but the diagnosis could only be verified for 13 patients (25%), in 40 cases only severe cervical schistosomiasis was diagnosed. Vulval/labial schistosomiasis was seen in specimens from young women. Infertility was reported in four patients with schistosomiasis of the Fallopian tubes. CONCLUSION: Genital schistosomiasis adds to the disease burden of women in all age groups. Pathological consequences due to the involvement of different genital organs can be damaging for the affected women. Clinical unawareness of genital schistosomiasis can lead to misdiagnosis and therefore false and ineffective therapy. In endemic areas cervical schistosomiasis should be considered as differential diagnosis of cancer

Expression of yeast lipid phosphatase Sac1p is regulated by phosphatidylinositol-4-phosphate

<p>Abstract</p> <p>Background</p> <p>Phosphoinositides play a central role in regulating processes at intracellular membranes. In yeast, a large number of phospholipid biosynthetic enzymes use a common mechanism for transcriptional regulation. Yet, how the expression of genes encoding lipid kinases and phosphatases is regulated remains unknown.</p> <p>Results</p> <p>Here we show that the expression of lipid phosphatase Sac1p in the yeast <it>Saccharomyces cerevisiae </it>is regulated in response to changes in phosphatidylinositol-4-phosphate (PI(4)P) concentrations. Unlike genes encoding enzymes involved in phospholipid biosynthesis, expression of the <it>SAC1 </it>gene is independent of inositol levels. We identified a novel 9-bp motif within the 5' untranslated region (5'-UTR) of <it>SAC1 </it>that is responsible for PI(4)P-mediated regulation. Upregulation of <it>SAC1 </it>promoter activity correlates with elevated levels of Sac1 protein levels.</p> <p>Conclusion</p> <p>Regulation of Sac1p expression via the concentration of its major substrate PI(4)P ensures proper maintenance of compartment-specific pools of PI(4)P.</p