Primary pelvic hydatid cyst in a postmenopausal female: a surgical challenge

Primary pelvic hydatid cysts are a rare entity and are often overlooked as a differential diagnosis of a pelvic-space-occupying lesion particularly in non-endemic regions. Unpreparedness and a hasty decision on the surgical approach may end in life-threatening complications and systemic dissemination of the disease. We report the case of a 55-year-old postmenopausal woman with a history of two previous unsuccessful surgeries to remove pelvic cystic lesions due to dense adhesions between the surrounding gut wall, bladder, and the cyst wall. Clinical and imaging findings failed to diagnose the nature of the cysts, and a laparotomy was contemplated. On the third surgical attempt, the clinical suspicion was considered and by meticulous dissection the cysts were removed thoroughly without undue complications. In the postoperative follow-up period there was no sign of disease recurrence or disseminatio

Primary pelvic hydatid cyst in a postmenopausal female: a surgical challenge

Primary pelvic hydatid cysts are a rare entity and are often overlooked as a differential diagnosis of a pelvic-space-occupying lesion particularly in non-endemic regions. Unpreparedness and a hasty decision on the surgical approach may end in life-threatening complications and systemic dissemination of the disease. We report the case of a 55-year-old postmenopausal woman with a history of two previous unsuccessful surgeries to remove pelvic cystic lesions due to dense adhesions between the surrounding gut wall, bladder, and the cyst wall. Clinical and imaging findings failed to diagnose the nature of the cysts, and a laparotomy was contemplated. On the third surgical attempt, the clinical suspicion was considered and by meticulous dissection the cysts were removed thoroughly without undue complications. In the postoperative follow-up period there was no sign of disease recurrence or disseminatio

Tribbles Pseudokinase 3 Induces Both Apoptosis and Autophagy in Amyloid-�-induced Neuronal Death

Amyloid-� (A�)-induced neuron death is considered central to the pathogenesis of Alzheimer’s disease (AD). Among several death modalities, autophagy and apoptosis play important roles in A�-induced neuron death suggesting that there may be regulatory mechanisms that initiate both cell death pathways. However, molecules that govern both pathways have not been identified. Here, we report that, upon A� treatment, tribbles pseudokinase 3 (Trib3, an ortholog of Drosophila Tribbles) is up-regulated in neurons both in vivo and in vitro. Increased Trib3 levels inhibited the activity of the kinase Akt by interacting with it. As a result, forkhead box O1 (FoxO1), a transcription factor that is negatively regulated by Akt, was activated, translocated to the nucleus, and induced the pro-apoptotic gene BCL2-like 11 (Bim). Conversely, FoxO1 responded to A� insult by binding to the Trib3 gene promoter, enhancing its expression. Our investigations further revealed that Trib3 also induces autophagy. Wefound that Trib3 indirectly activates unc-51-like autophagy-activating kinase1 (Ulk1) by impeding phosphorylation of, and thus inactivating, a negative regulator of Ulk1, mechanistic target of rapamycin. Ulk1 activation augmented autophagosome formation and reduced autophagy flux. Thus, Trib3 was required for formation of autophagosomes, which accumulated in neurons as autophagic flux was thwarted. Most importantly, silencing endogenous Trib3 strongly protected neurons from A� insult. Our results suggest that a self-amplifying feed-forward loop among Trib3, Akt, and FoxO1 in A�-treated neurons induces both apoptosis and autophagy, culminating in neuron death. Thus, Trib3 may serve as a potential therapeutic target for AD

Regulation of cytoskeletal proteins by thyroid hormone during neuronal maturation and differentiation

Primary cultures of neurons from 16- to 17-day-old embryonic rat cerebra were maintained for 3 weeks in thyroid hormone deficient (TH<SUB>def</SUB>) and thyroid hormone supplemented (TH<SUB>sup</SUB>) media to investigate how TH regulates the cytoskeletal (CSK) proteins during neuronal differentiation and maturation. Two distinct phases of regulation of triton-insoluble CSK-proteins by TH were discernible - an early phase (days 4-8 of culture) when TH-deficiency resulted in down-regulation of these proteins and a late phase (days 16-20) involving up-regulation of these proteins. In contrast, the triton-soluble non-CSK proteins always remained up-regulated by TH. The two main effects of TH-deficiency were retarded neurite outgrowth and altered neuronal morphology. Of all the CSK proteins, actin was found to be predominantly sensitive. Alterations in the level of CSK actin during neuronal maturation were found to be parallel to changes in steady-state level of actin mRNA as well as actin synthesis. However, these TH-induced changes (up-regulation of actin during the early phase and down-regulation during the late phase) did not lead to parallel changes in the level of soluble G-actin which was comparable at both days 8 and 16 in TH<SUB>def</SUB> and TH<SUB>sup</SUB> cultures. Quantitation of different forms of intracellular actin revealed that G-actin level declined by about 50% between days 8 and 16. In the case of TH<SUB>sup</SUB> neurons, this reduction in G-actin was accompanied by a parallel increase in the non-CSK F-actin, whereas TH-deficiency resulted in a corresponding increase in CSK F-actin during the terminal differentiation of neurons. Thus TH regulates the biogenesis of CSK-proteins with a predominant effect on actin and the transformation of G-actin into non-CSK F-actin appears to be the key step in neuronal maturation which is affected by hypothyroidism

Sedimentation of metals in Sundarban mangrove ecosystem : dominant drivers and environmental risks

Metal contamination from upstream river water is a threat to coastal and estuarine ecosystem. The present study was undertaken to unveil sedimentation processes and patterns of heavy metal deposition along the salinity gradient of a tropical estuary and its mangrove ecosystem. Sediment columns from three representative sites of differential salinity, anthropogenic interference, and sediment deposition pattern were sampled and analyzed for grain size distribution and metal concentrations as a function of depth. Sediments were dominantly of silty-medium sand texture. A suite of fluvial and alluvial processes, and marine depositional forcing control the sediment deposition and associated heavy metal loading in this estuary. The depth profile revealed a gradual increase in heavy metal accumulation in recent top layer sediments and smaller fractions (silt + clay), irrespective of tidal regimes. Alluvial processes and long tidal retention favor accumulation of heavy metals. Enrichment factor (0.52-15), geo-accumulation index (1.4-5.8), and average pollution load index (PLI = 2.0) indicated moderate to higher heavy metal contamination status of this estuary. This study showed that alluvial processes acted as dominant drivers for the accumulation of metals in sediments, which prevailed over the influence of marine processes. Longer tidal retention of the water column favored more accumulation of heavy metals. Metal accumulation in the sediments entails a potential risk of bioaccumulation and biomagnification through the food web, and may increasingly impact estuarine ecology, economy, and ultimately human health

Multifunctional transcriptional coactivator PC4 is a global co-regulator of p53-dependent stress response and gene regulation

Abstract Human positive coactivator 4 (PC4), a multifunctional chromatin-associated protein, is known to directly interact with p53 and modulate expressions of a few p53-dependent genes. However, the role of PC4 in p53's myriad of other regulatory functions is not known. The p53–PC4 interaction was selectively perturbed by a small peptide which led to abrogation of genotoxic stress-induced up-regulation of many p53-dependent genes and reduction of apoptosis in A549 cells. Over-expression of a PC4 point mutant, incapable of binding p53, recapitulated many of the effects of the peptide. Global gene expression profiling in A549 cells, upon peptide treatment, revealed PC4's involvement in the regulation of many p53-dependent pathways, including the Hippo pathway. Introduction of the peptide in neuronal cells significantly reduced its amyloid-β-induced death. Thus, PC4 emerges as a global co-regulator of p53 and a therapeutic target against pathogeneses where the p53-dependent cell death process plays a crucial role

Efficacy of cyclin dependent kinase 4 inhibitors as potent neuroprotective agents against insults relevant to Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease with no cure till today. Aberrant activation of cell cycle regulatory proteins is implicated in neurodegenerative diseases including AD. We and others have shown that Cyclin dependent kinase 4 (Cdk4) is activated in AD brain and is required for neuron death. In this study, we tested the efficiency of commercially available Cdk4 specific inhibitors as well as a small library of synthetic molecule inhibitors targeting Cdk4 as neuroprotective agents in cellular models of neuron death. We found that several of these inhibitors significantly protected neuronal cells against death induced by nerve growth factor (NGF) deprivation and oligomeric beta amyloid (Aβ) that are implicated in AD. These neuroprotective agents inhibit specifically Cdk4 kinase activity, loss of mitochondrial integrity, induction of pro-apoptotic protein Bim and caspase3 activation in response to NGF deprivation. The efficacies of commercial and synthesized inhibitors are comparable. The synthesized molecules are either phenanthrene based or naphthalene based and they are synthesized by using Pschorr reaction and Buchwald coupling respectively as one of the key steps. A number of molecules of both kinds block neurodegeneration effectively. Therefore, we propose that Cdk4 inhibition would be a therapeutic choice for ameliorating neurodegeneration in AD and these synthetic Cdk4 inhibitors could lead to development of effective drugs for AD

Dietary arsenic consumption and urine arsenic in an endemic population: response to improvement of drinking water quality in a 2-year consecutive study

We assessed the association between arsenic intake through water and diet, and arsenic levels in first morning-void urine under variable conditions of water contamination. This was done in a 2-year consecutive study in an endemic population. Exposure of arsenic through water and diet was assessed for participants using arsenic-contaminated water (a parts per thousand yen50 mu g L-1) in a first year (group I) and for participants using water lower in arsenic (< 50 mu g L-1) in the next year (group II). Participants with and without arsenical skin lesions were considered in the statistical analysis. Median dose of arsenic intake through drinking water in groups I and II males was 7.44 and 0.85 mu g kg body wt.(-1) day(-1) (p < 0.0001). In females, it was 5.3 and 0.63 mu g kg body wt.(-1) day(-1) (p < 0.0001) for groups I and II, respectively. Arsenic dose through diet was 3.3 and 2.6 mu g kg body wt.(-1) day(-1) (p = 0.088) in males and 2.6 and 1.9 mu g kg body wt.(-1) day(-1) (p = 0.0081) in females. Median arsenic levels in urine of groups I and II males were 124 and 61 mu g L-1 (p = 0.052) and in females 130 and 52 mu g L-1 (p = 0.0001), respectively. When arsenic levels in the water were reduced to below 50 mu g L-1 (Indian permissible limit), total arsenic intake and arsenic intake through the water significantly decreased, but arsenic uptake through the diet was found to be not significantly affected. Moreover, it was found that drinking water mainly contributed to variations in urine arsenic concentrations. However, differences between male and female participants also indicate that not only arsenic uptake, but also many physiological factors affect arsenic behavior in the body and its excretion. As total median arsenic exposure still often exceeded 3.0 mu g kg body wt.(-1) day(-1) (the permissible lower limit established by the Joint Expert Committee on Food Additives) after installation of the drinking water filters, it can be concluded that supplying the filtered water only may not be sufficient to minimize arsenic availability for an already endemic population

A cumulative assessment of plant growth stages and selenium supplementation on arsenic and micronutrients accumulation in rice grains

Arsenic (As) accumulation in rice grain and subsequent transmission into the food chain is a major global concern. Numerous attempts to minimize As accumulation in rice have been researched till date. The current investigation evaluates the relative susceptibility of different growth stages of rice plant to As stress in terms of As accumulation in grain at maturity using sixty treatment combinations. Our findings suggest that supplementing with selenium (Se) resulted in minimizing As content significantly (at P grain filling > maximum tillering. Our findings also showed that Se primed rice plants restricts majority of As accumulation in the root itself and minimizes As translocation to the above ground part. The results of this study shows that cultivation of Se primed seeds can be (i) an effective means to minimize As accumulation in rice, and (ii) potential mode of biofortification of rice grain with essential nutrient elements {iron (8.47–10.17 mg L-1), zinc (7.14–8.05 mg L-1), manganese (17.92–19.71 mg L-1) and copper (3.18–3.28 mg L-1)} improving the recommended dietary intake of micronutrients, an invaluable strategy especially for malnourished rice dependent populations. Using machine learning this study also predicts that the Se concentration of 0.862 mg L−1 could be the most effective input in minimizing As content and enhancing other micronutrient content, irrespective of As stress