Pediatric carcinoma of rectum - Varanasi experience

Background : Primary gastrointestinal system malignancies constitute approximately 2% of pediatric neoplasm and of these; colorectal carcinoma is the second most common malignancy. This is one of the rarer diseases in children. Aim : We reviewed our records to study the clinical features, outcome and the follow-up of this condition with evaluation of the prognostic factors. Settings and Design: Tertiary care Pediatric Surgery centre. Retrospective study. Materials and Methods : The data of all patients with diagnosis of colorectal carcinoma from January 1986 to January 2006 were reviewed. The confirmation of the diagnosis was by biopsy from the lesion. The age, sex, family history, clinical features, response to the treatment and follow-up were studied. Results : There were four male patients. All had bleeding per rectum as the presenting complaint. Three patients had advanced disease at presentation. All the patients had signet cell adenocarcinoma. The two patients expired and one was lost to follow-up. One patient is alive after one year of follow up and is receiving treatment. Conclusion : Colorectal cancer in children though rare can be a reality, hence any children presenting with pain in abdomen along with doubtful history of constipation and rectal bleeding should be examined carefully with special emphasis on digital rectal examination

Pediatric carcinoma of rectum - Varanasi experience

Background : Primary gastrointestinal system malignancies constitute approximately 2% of pediatric neoplasm and of these; colorectal carcinoma is the second most common malignancy. This is one of the rarer diseases in children. Aim : We reviewed our records to study the clinical features, outcome and the follow-up of this condition with evaluation of the prognostic factors. Settings and Design: Tertiary care Pediatric Surgery centre. Retrospective study. Materials and Methods : The data of all patients with diagnosis of colorectal carcinoma from January 1986 to January 2006 were reviewed. The confirmation of the diagnosis was by biopsy from the lesion. The age, sex, family history, clinical features, response to the treatment and follow-up were studied. Results : There were four male patients. All had bleeding per rectum as the presenting complaint. Three patients had advanced disease at presentation. All the patients had signet cell adenocarcinoma. The two patients expired and one was lost to follow-up. One patient is alive after one year of follow up and is receiving treatment. Conclusion : Colorectal cancer in children though rare can be a reality, hence any children presenting with pain in abdomen along with doubtful history of constipation and rectal bleeding should be examined carefully with special emphasis on digital rectal examination

Local recurrence and distant metastases 18 years after resection of the greater omentum hemangiopericytoma

<p>Abstract</p> <p>Background</p> <p>Hemangiopericytoma occurs with increasing frequency in 5^thdecade of life and has prediction for retroperitoneum and extremities. A case of a local recurrence and metastases of hemangiopericytoma is described.</p> <p>Case presentation</p> <p>Recurrence of hemangiopericytoma in the greater omentum and the jejunal mesentery as well as metastases in the retroperitoneal space were diagnosed in a 61-year-old patient who had a hemangiopericytoma of the greater omentum excised 18 years before.</p> <p>Conclusion</p> <p>Because of the rarity of this disease and its typical clinical course associated with late recurrence and metastases, the authors decided to present this case emphasizing the necessity of systematic oncological follow-up after the end of treatment.</p

Mapping private pharmacies and their characteristics in Ujjain district, Central India

<p>Abstract</p> <p>Background</p> <p>In India, private pharmacies are ubiquitous yet critical establishments that facilitate community access to medicines. These are often the first points of treatment seeking in parts of India and other low income settings around the world. The characteristics of these pharmacies including their location, drug availability, human resources and infrastructure have not been studied before. Given the ubiquity and popularity of private pharmacies in India, such information would be useful to harness the potential of these pharmacies to deliver desirable public health outcomes, to facilitate regulation and to involve in initiatives pertaining to rational drug use. This study was a cross sectional survey that mapped private pharmacies in one district on a geographic information system and described relevant characteristics of these units.</p> <p>Methods</p> <p>This study of pharmacies was a part of larger cross sectional survey carried out to map all the health care providers in Ujjain district (population 1.9 million), Central India, on a geographic information system. Their location vis-à-vis formal providers of health services were studied. Other characteristics like human resources, infrastructure, clients and availability of tracer drugs were also surveyed.</p> <p>Results</p> <p>A total 475 private pharmacies were identified in the district. Three-quarter were in urban areas, where they were concentrated around physician practices. In rural areas, pharmacies were located along the main roads. A majority of pharmacies simultaneously retailed medicines from multiple systems of medicine. Tracer parenteral antibiotics and injectable steroids were available in 83.7% and 88.7% pharmacies respectively. The proportion of clients without prescription was 39.04%. Only 11.58% of staff had formal pharmacist qualifications. Power outages were a significant challenge.</p> <p>Conclusion</p> <p>This is the first mapping of pharmacies & their characteristics in India. It provides evidence of the urban dominance and close relationship between healthcare provider location and pharmacy location. The implications of this relationship are discussed. The study reports a lack of qualified staff in the presence of a high proportion of clients attending without a prescription. The study highlights the need for the better implementation of regulation. Besides facilitating regulation & partnerships, the data also provides a sampling frame for future interventional studies on these pharmacies.</p

Analysis of quality raw data of second generation sequencers with Quality Assessment Software

<p>Abstract</p> <p>Background</p> <p>Second generation technologies have advantages over Sanger; however, they have resulted in new challenges for the genome construction process, especially because of the small size of the reads, despite the high degree of coverage. Independent of the program chosen for the construction process, DNA sequences are superimposed, based on identity, to extend the reads, generating contigs; mismatches indicate a lack of homology and are not included. This process improves our confidence in the sequences that are generated.</p> <p>Findings</p> <p>We developed Quality Assessment Software, with which one can review graphs showing the distribution of quality values from the sequencing reads. This software allow us to adopt more stringent quality standards for sequence data, based on quality-graph analysis and estimated coverage after applying the quality filter, providing acceptable sequence coverage for genome construction from short reads.</p> <p>Conclusions</p> <p>Quality filtering is a fundamental step in the process of constructing genomes, as it reduces the frequency of incorrect alignments that are caused by measuring errors, which can occur during the construction process due to the size of the reads, provoking misassemblies. Application of quality filters to sequence data, using the software Quality Assessment, along with graphing analyses, provided greater precision in the definition of cutoff parameters, which increased the accuracy of genome construction.</p

Antidepressant stimulation of CDP-diacylglycerol synthesis does not require monoamine reuptake inhibition

<p>Abstract</p> <p>Background</p> <p>Recent studies demonstrate that diverse antidepressant agents increase the cellular production of the nucleolipid CDP-diacylglycerol and its synthetic derivative, phosphatidylinositol, in depression-relevant brain regions. Pharmacological blockade of downstream phosphatidylinositide signaling disrupted the behavioral antidepressant effects in rats. However, the nucleolipid responses were resistant to inhibition by serotonin receptor antagonists, even though antidepressant-facilitated inositol phosphate accumulation was blocked. Could the neurochemical effects be additional to the known effects of the drugs on monoamine transmitter transporters? To examine this question, we tested selected agents in serotonin-depleted brain tissues, in PC12 cells devoid of serotonin transporters, and on the enzymatic activity of brain CDP-diacylglycerol synthase - the enzyme that catalyzes the physiological synthesis of CDP-diacylglycerol.</p> <p>Results</p> <p>Imipramine, paroxetine, and maprotiline concentration-dependently increased the levels of CDP-diacylglycerol and phosphatidylinositides in PC12 cells. Rat forebrain tissues depleted of serotonin by pretreatment with <it>p</it>-chlorophenylalanine showed responses to imipramine or maprotiline that were comparable to respective responses from saline-injected controls. With fluoxetine, nucleolipid responses in the serotonin-depleted cortex or hippocampus were significantly reduced, but not abolished. Each drug significantly increased the enzymatic activity of CDP-diacylglycerol synthase following incubations with cortical or hippocampal brain tissues.</p> <p>Conclusion</p> <p>Antidepressants probably induce the activity of CDP-diacylglycerol synthase leading to increased production of CDP-diacylglycerol and facilitation of downstream phosphatidylinositol synthesis. Phosphatidylinositol-dependent signaling cascades exert diverse salutary effects in neural cells, including facilitation of BDNF signaling and neurogenesis. Hence, the present findings should strengthen the notion that modulation of brain phosphatidylinositide signaling probably contributes to the molecular mechanism of diverse antidepressant medications.</p

Agronomic Management of Indigenous Mycorrhizas

Many of the advantages conferred to plants by arbuscular mycorrhiza (AM) are associated to the ability of AM plants to explore a greater volume of soil through the extraradical mycelium. Sieverding (1991) estimates that for each centimetre of colonized root there is an increase of 15 cm3 on the volume of soil explored, this value can increase to 200 cm3 depending on the circumstances. Due to the enhancement of the volume of soil explored and the ability of the extraradical mycelium to absorb and translocate nutrients to the plant, one of the most obvious and important advantages resulting from mycorrhization is the uptake of nutrients. Among of which the ones that have immobilized forms in soil, such as P, assume particular significance. Besides this, many other benefits are recognized for AM plants (Gupta et al, 2000): water stress alleviation (Augé, 2004; Cho et al, 2006), protection from root pathogens (Graham, 2001), tolerance to toxic heavy metals and phytoremediation (Audet and Charest, 2006; Göhre and Paszkowski, 2006), tolerance to adverse conditions such as very high or low temperature, high salinity (Sannazzaro et al, 2006), high or low pH (Yano and Takaki, 2005) or better performance during transplantation shock (Subhan et al, 1998). The extraradical hyphae also stabilize soil aggregates by both enmeshing soil particles (Miller e Jastrow, 1992) and producing a glycoprotein, golmalin, which may act as a glue-like substance to adhere soil particles together (Wright and Upadhyaya, 1998). Despite the ubiquous distribution of mycorrhizal fungi (Smith and Read, 2000) and only a relative specificity between host plants and fungal isolates (McGonigle and Fitter, 1990), the obligate nature of the symbiosis implies the establishment of a plant propagation system, either under greenhouse conditions or in vitro laboratory propagation. These techniques result in high inoculum production costs, which still remains a serious problem since they are not competitive with production costs of phosphorus fertilizer. Even if farmers understand the significance of sustainable agricultural systems, the reduction of phosphorus inputs by using AM fungal inocula alone cannot be justified except, perhaps, in the case of high value crops (Saioto and Marumoto, 2002). Nurseries, high income horticulture farmers and no-agricultural application such as rehabilitation of degraded or devegetated landscapes are examples of areas where the use of commercial inoculum is current. Another serious problem is quality of commercial available products concerning guarantee of phatogene free content, storage conditions, most effective application methods and what types to use. Besides the information provided by suppliers about its inoculum can be deceiving, as from the usually referred total counts, only a fraction may be effective for a particular plant or in specific soil conditions. Gianinazzi and Vosátka (2004) assume that progress should be made towards registration procedures that stimulate the development of the mycorrhizal industry. Some on-farm inoculum production and application methods have been studied, allowing farmers to produce locally adapted isolates and generate a taxonomically diverse inoculum (Mohandas et al, 2004; Douds et al, 2005). However the inocula produced this way are not readily processed for mechanical application to the fields, being an obstacle to the utilization in large scale agriculture, especially row crops, moreover it would represent an additional mechanical operation with the corresponding economic and soil compaction costs. It is well recognized that inoculation of AM fungi has a potential significance in not only sustainable crop production, but also environmental conservation. However, the status quo of inoculation is far from practical technology that can be widely used in the field. Together a further basic understanding of the biology and diversity of AM fungi is needed (Abbott at al, 1995; Saito and Marumoto, 2002). Advances in ecology during the past decade have led to a much more detailed understanding of the potential negative consequences of species introductions and the potential for negative ecological consequences of invasions by mycorrhizal fungi is poorly understood. Schwartz et al, (2006) recommend that a careful assessment documenting the need for inoculation, and the likelihood of success, should be conducted prior to inoculation because inoculations are not universally beneficial. Agricultural practices such as crop rotation, tillage, weed control and fertilizer apllication all produce changes in the chemical, physical and biological soil variables and affect the ecological niches available for occupancy by the soil biota, influencing in different ways the symbiosis performance and consequently the inoculum development, shaping changes and upset balance of native populations. The molecular biology tools developed in the latest years have been very important for our perception of these changes, ensuing awareness of management choice implications in AM development. In this context, for extensive farming systems and regarding environmental and economic costs, the identification of agronomic management practices that allow controlled manipulation of the fungal community and capitalization of AM mutualistic effect making use of local inoculum, seem to be a wise option for mycorrhiza promotion and development of sustainable crop production

Influence of Various Polymorphic Variants of Cytochrome P450 Oxidoreductase (POR) on Drug Metabolic Activity of CYP3A4 and CYP2B6

Cytochrome P450 oxidoreductase (POR) is known as the sole electron donor in the metabolism of drugs by cytochrome P450 (CYP) enzymes in human. However, little is known about the effect of polymorphic variants of POR on drug metabolic activities of CYP3A4 and CYP2B6. In order to better understand the mechanism of the activity of CYPs affected by polymorphic variants of POR, six full-length mutants of POR (e.g., Y181D, A287P, K49N, A115V, S244C and G413S) were designed and then co-expressed with CYP3A4 and CYP2B6 in the baculovirus-Sf9 insect cells to determine their kinetic parameters. Surprisingly, both mutants, Y181D and A287P in POR completely inhibited the CYP3A4 activity with testosterone, while the catalytic activity of CYP2B6 with bupropion was reduced to approximately ∼70% of wild-type activity by Y181D and A287P mutations. In addition, the mutant K49N of POR increased the CLint (Vmax/Km) of CYP3A4 up to more than 31% of wild-type, while it reduced the catalytic efficiency of CYP2B6 to 74% of wild-type. Moreover, CLint values of CYP3A4-POR (A115V, G413S) were increased up to 36% and 65% of wild-type respectively. However, there were no appreciable effects observed by the remaining two mutants of POR (i.e., A115V and G413S) on activities of CYP2B6. In conclusion, the extent to which the catalytic activities of CYP were altered did not only depend on the specific POR mutations but also on the isoforms of different CYP redox partners. Thereby, we proposed that the POR-mutant patients should be carefully monitored for the activity of CYP3A4 and CYP2B6 on the prescribed medication