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als about this possibility. This may shorten the time to diagnosis and treatment commencement, and thereby alleviate both GI and ASD symptoms through reducing pain, stress, or discomfort. Furthermore, this may also protect children against unnecessary dietary experiments and restrictions that have no medical indications. A personalized approach to each patient is necessary. Our understanding of ASDs has come a long way, but further studies and more systematic research are warranted.Pneumocystis pneumonia (PCP) is well known and described in AIDS patients. Due to the increasing use of cytotoxic and immunosuppressive therapies, the incidence of this infection has dramatically increased in the last years in patients with other predisposing immunodeficiencies and remains an important cause of morbidity and mortality in solid-organ transplant (SOT) recipients. PCP in HIV-negative patients, such as SOT patients, harbors some specificity compared to AIDS patients, which could change the medical management of these patients. This article summarizes the current knowledge on the epidemiology, risk factors, clinical manifestations, diagnoses, prevention, and treatment of Pneumocystis pneumonia in solid-organ transplant recipients, with a particular focus on the changes caused by the use of post-transplantation prophylaxis.
Currently there is an urgent need to develop new classes of antimicrobial agents with different mechanisms of action from conventionally antibiotics used for the control of pathogenic microorganisms. The acylpolyamine called VdTX-I was isolated from the venom of the tarantula
, and first described with activity as an antagonist of nicotinic cholinergic receptors. The main objective of this study was to investigate the antimicrobial activity found in the venom of the spider, with emphasis on the toxin VdTX-I.
Antimicrobial assays were performed in 96 well plates culture against 14 micro-organisms (fungi, yeasts and bacteria), which were tested concentrations from 0.19 to 100μM of VdTX-I. After qualitative analysis, dose-response curve assays were performed in bacterial kill curve using MTT reagent and hemolytic assay.
The antimicrobial activity of the VdTX-I toxin was observed in 12 tested species of
,
,
and
. The toxicity had a dose-response at 3.12µM - 100μM in
,
,
and
VdTX-I took about 5min to inhibit bacterial growth, which was faster than streptomycin. The toxin showed no hemolytic activity between 0.19 and 100μM. At 2.5µg/mL of toxin it was observed no growth inhibition against a mammalian cell lineage.
The VdTX-I toxin has a significant antimicrobial activity, with broad spectrum, and is experimentally inert to mammalian blood cells.
This paper explores the antimicrobial potential of the spider toxin VdTX-I, which can provide a new model to design new antimicrobial drugs.
This paper explores the antimicrobial potential of the spider toxin VdTX-I, which can provide a new model to design new antimicrobial drugs.
To evaluate the clinical safety and efficacy of the retrograde perfusion technique in kidney transplantation.
Between January 2001 and June 2011, 24 cases of kidney transplantation with kidneys perfused using the retrograde perfusion technique due to renal artery variations or injury were selected as the observation group (retrograde perfussion group, RP group). Twenty-two cases of kidney transplantation via conventional perfusion were chosen as the control group (antegrade perfussion group, AP group). There were no statistically significant differences in donor data between the two groups. Cold ischemia time, warm ischemia time, renal perfusion time, amount of perfusion fluid, acute renal tubular necrosis, wound infection, urinary fistula, graft kidney function, and the 1-year, 3-year, and 5-year survival rates for the grafted kidney in both groups were observed and recorded.
The kidney perfusion time was shorter in the RP group than that in the AP group (3.14 ± 1.00 vs. 5.02 ± 1.15 min,
= 0.030). There were 10 cases of acute renal tubule necrosis in the RP group and 5 in the AP group. The length of hospital stay was 40±14d in the RP group and 25±12d in the AP group. The follow-up time was 3.5-8.5 years (mean 6.25years). The 1-, 3-, and 5-year survival rates for the grafted kidney were 95.8%, 75.5%, and 65.5% in the RP group and 97.1%, 82.5%, and 68.4% in the AP group, respectively (
>0.05).
This study indicates that retrograde perfusion is safe and practicable for cadaveric kidney harvesting and can be regarded as a better alternative or remedial measure for a poorly perfused kidney due to vascular deformity or injury.
This study indicates that retrograde perfusion is safe and practicable for cadaveric kidney harvesting and can be regarded as a better alternative or remedial measure for a poorly perfused kidney due to vascular deformity or injury.Myalgic encephalitis (M.E.) is a common condition, the cause of which is not known and there are no treatments available. Brusatol mouse In this study the national patient support group Action for M.E. sought the opinions of their members via an online survey as to what they felt should be future priorities for M.E.
Respondents were asked what they considered first, second and third research priorities to be from a list of 13 pre-defined options. Individuals were invited to provide additional free text comments about Action for M.E.'s research priorities in general. Of the 1144 respondents 822 had M.E.; 94 were a supporting a member of Action for M.E. ; 66 were carers for someone with M.E.; 26 were professionals with an interest in M.E.; 136 had a family member or colleague with M.E. Individuals selected more than one category as applicable. The top five research priorities identified were disease processes to achieve a better understanding of the causes of M.E.; more effective treatments; faster and more accurate diagnosiuals affected by M.E. have clear views regarding priorities for research investment. These have informed Action for M.E.'s ongoing research strategy and ultimately will inform national and international research priorities.Arsenic and nicotine exposure has been a major health concern globally. Individually both these toxicants increase the risk to various diseases including cancers. However, limited information exists on the co-exposure. In this study, we evaluate the effects of their individual and combined exposure and if co-exposure to these toxicants might have a synergism or antagonism. Male rats were exposed to a very low dose of arsenic (25 ppm in drinking water) or nicotine (0.25 mg/kg, sub-cutaneously) for a period of 5 months and post exposure various biochemical variables indicative of oxidative stress and apoptosis evaluated. Almost all glutathione linked enzymes showed marked alteration in individual as well as co-exposure treated groups. While serum creatinine and apoptosis indicator, lactate dehydrogenase (LDH) were significantly increased in both treatments, an additive effect was noted in co-exposure group. A similar trend was also seen in brain and liver but not in kidneys. Gene expression studies showed marked reduction in catalase, Cu-Zn SOD, GST, there was a significant up regulation in Bax, caspase 3 in various tissues along with urinary 8-OHdG levels, indicative of DNA damage and apoptosis. Interestingly, a decrease in liver arsenic concentration was noted in co-exposed group compared to arsenic alone exposed group. In conclusion, the present study suggests that arsenic and nicotine exhibited significant toxicity during individual exposure whereas co-exposure to these toxins showed variable conditions (indicative of both synergism and antagonism) in male rats.In the present study, α-tocopherol succinate (TOS) conjugated dextran (Dex-TOS) was synthesized and characterized by fourier transform infrared (FT-IR) spectroscopy, ¹H nuclear magnetic resonance (¹H NMR), dynamic light scattering (DLS) and fluorescence spectroscopy. Dex-TOS could form nanoscaled micelles in aqueous medium. The critical micelle concentration (CMC) is 0.0034 mg/mL. Doxorubicin (Dox) was selected as a model drug. Dox-loaded Dex-TOS (Dex-TOS/Dox) micelles were prepared by a dialysis method. The size of Dex-TOS/Dox micelles increased from 295 to 325 nm with the Dox-loading content increasing from 4.21% to 8.12%. The Dex-TOS/Dox micelles were almost spherical in shape, as determined by transmission electron microscopy (TEM). In vitro release demonstrated that Dox release from the micelles was in a sustained manner for up to 96 h. The cellular uptake of Dex-TOS/Dox micelles in human nasopharyngeal epidermoid carcinoma (KB) cells is an endocytic process determined by confocal laser scanning microscopy (CLSM). Moreover, Dex-TOS/Dox micelles exhibited comparable cytotoxicity in contrast with doxorubicin hydrochloride. These results suggested that Dex-TOS micelles could be a promising carrier for drug delivery.
Targeted kinase inhibitors are an important class of agents in anticancer therapeutics, but their limited tolerability hampers their clinical performance. Identification of the molecular mechanisms underlying the development of adverse reactions will be helpful in establishing a rational method for the management of clinically adverse reactions. Here, we selected sunitinib as a model and demonstrated that the molecular mechanisms underlying the adverse reactions associated with kinase inhibitors can efficiently be identified using a systems toxicological approach.
First, toxicological target candidates were short-listed by comparing the human kinase occupancy profiles of sunitinib and sorafenib, and the molecular mechanisms underlying adverse reactions were predicted by sequential simulations using publicly available mathematical models. Next, to evaluate the probability of these predictions, a clinical observation study was conducted in six patients treated with sunitinib. Finally, mouse experiments werenal method for the management of these adverse reactions.
Regulation of gene expression by microRNAs (miRNAs) is critical for determining cellular fate and function. Dysregulation of miRNA expression contributes to the development and progression of multiple diseases. miRNA can target multiple mRNAs, making deconvolution of the effects of miRNA challenging and the complexity of regulation of cellular pathways by miRNAs at the functional protein level remains to be elucidated. Therefore, we sought to determine the effects of expression of miRNAs in breast and ovarian cancer cells on cellular pathways by measuring systems-wide miRNA perturbations to protein and phosphoproteins.
We measure protein level changes by reverse-phase protein array (RPPA) in MDA-MB-231, SKOV3.ip1 and HEYA8 cancer cell lines transfected by a library of 879 human miRNA mimics.
The effects of multiple miRNAs-protein networks converged in five broad functional clusters of miRNA, suggesting a broad overlap of miRNA action on cellular pathways. Detailed analysis of miRNA clusters revealed novel miRNA/cell cycle protein networks, which we functionally validated.
phosphoprotein network estimation using Gaussian graphical modeling, using no priors, revealed known and novel protein interplay, which we also observed in patient ovarian tumor proteomic data. We identified several miRNAs that have pluripotent activities across multiple cellular pathways. In particular we studied miR-365a whose expression is associated with poor survival across several cancer types and demonstrated that anti-miR-365 significantly reduced tumor formation in animal models.
Mapping of miRNA-induced protein and phosphoprotein changes onto pathways revealed new miRNA-cellular pathway connectivity, paving the way for targeting of dysregulated pathways with potential miRNA-based therapeutics.
Mapping of miRNA-induced protein and phosphoprotein changes onto pathways revealed new miRNA-cellular pathway connectivity, paving the way for targeting of dysregulated pathways with potential miRNA-based therapeutics.
