Evaluation of multikinase inhibitor LDN193189 induced hepatotoxicity in teleost fish Poecilia latipinna

Currently, scientists show keen interest in the drugs that inhibit multiple kinases, LDN193189, being an example. It combats certain cancers in vitro as well as in vivo, making it a prerequisite for researchers to study the toxic potential of this drug in animal models. As most of the drugs metabolized by liver cause hepatic injury, LDN193189-induced hepatotoxicity was examined using a teleost fish, Poecilia latipinna. As a prelude, calculation of LD₅₀ showed a value of 95.22?mg/kg body weight and three doses were decided based on it for further evaluations. All these groups were tested for antioxidant enzyme levels and were significantly raised for mid- and high-dose group. Similar trend was recorded for ALP, AST, and ALT levels. Furthermore, some key indicators of drug metabolism in liver were tested for their expression in response to LDN193189 treatment. Among these, Cyt-C, CYP3A4, CYP1B1 and CYP1A1 were elevated in mid- and high dose, except CYP21A1, which declined remarkably. Moreover, histological profile of the liver reflected high degree of inflammation due to drug treatment, but this was found only at high dose. In summary, LDN193189, at 2.5?mg/kg body weight, did not cause any adverse hepatotoxicity, rendering it safe for use as an anti-proliferative agent – an activity for which it has already shown promising results in the same animal model. The low-dose group previously studied for its anti-proliferative property showed no adverse effect in liver, whereas the mid- and high dose induced moderate or severe hepatotoxicity in P. latipinna.     

WHO framework convention on tobacco control and its implementation in South-East Asia region

The birth of the WHO Framework Convention on Tobacco Control (WHO FCTC) took place in response to the global tobacco epidemic and it became the most important global tobacco control instrument. Duly recognizing tobacco use as an important public health problem and in the wake of rising prevalence of and mortality related to tobacco use, almost all Member States of the South-East Asia Region signed and ratified the WHO FCTC. Following the ratification, Member countries have enacted comprehensive national tobacco control laws and regulations. Most countries have covered some important provisions, such as tax and price measures, smoke-free places, health warnings, a ban on tobacco advertising and promotion, and a ban on tobacco sales to minors. In spite of innumerable constraints and challenges, particularly human, infrastructural and financial resources, Member countries have been doing their best to enforce those legislations and regulations as effectively as possible. In order to educate the general public on the harmful effects of tobacco, mass health campaigns have been organized which are being continued and sustained. However, some of the important areas that need attention in due course of time are tax raises, illicit trade, tobacco industry interference and alternate cropping systems. All Member States in the Region are striving harder to achieving the goals and provisions of the Framework Convention through actively engaging all relevant sectors and addressing the tobacco issue holistically, and thus protecting the present and future generations from the devastating health, social, economic and environmental consequences of tobacco consumption and exposure to tobacco smoke.     

Anticonvulsant and antioxidant actions of trimetazidine in pentylenetetrazole-induced kindling model in mice

The present study was carried out to investigate the effect of trimetazidine on the course of pentylenetetrazole (PTZ)-induced chemical kindling and oxidative stress markers in PTZ-kindled mice. Kindling was induced by repeated injections of a subconvulsive dose of PTZ (30?mg?kg, i.p.) on alternate days for 5?weeks or until stage 4 of the seizure score was evoked on three consecutive administrations. Trimetazidine was administered daily in three doses (5, 10 and 20?mg/kg) per orally (p.o.) along with alternate-day PTZ. Following PTZ kindling, oxidative stress parameters, i.e. levels of malondialdehyde (MDA) and reduced glutathione (GSH), were assessed in isolated homogenized whole brain tissue. The results showed that PTZ treatment progressively increased the seizure score in control mice. Biochemical analysis revealed a significant increase in MDA levels and decreased GSH levels in the brain homogenate of PTZ-kindled mice. Daily treatment with trimetazidine in doses of 10 and 20?mg/kg significantly decreased the PTZ-induced seizure score. However, a low dose of trimetazidine (5?mg/kg) failed to improve the seizure score. Pretreatment of trimetazidine in all doses showed an ameliorating effect on biochemical alteration induced by PTZ treatment. The results of the present study indicate the potential anticonvulsant activity of trimetazidine against PTZ-induced kindling in mice.     

Socioeconomic and gender disparities in anal cancer diagnosis and treatment

Background and objectives

We investigated whether receipt of radiation in patients with anal carcinoma is related to income level and other demographic factors.

Central line-associated bloodstream infection among children with biliary atresia listed for liver transplantation

BACKGROUND Pre-transplant nutrition is a key driver of outcomes following liver transplantation in children.Patients with biliary atresia(BA) may have difficulty achieving satisfactory weight gain with enteral nutrition alone,and parenteral nutrition(PN) may be indicated.While PN has been shown to improve anthropometric parameters of children with BA listed for liver transplantation,less is known about the risks,particularly infectious,associated with this therapy among this specific group of patients.AIM To describe the incidence,microbiology,and risk factors of central line-associated bloodstream infection(CLABSI) among children with BA listed for liver transplantation.METHODS Retrospective review of children aged ≤ 2-years of age with BA who were listed for primary liver transplantation at Texas Children's Hospital from 2008 through2015(n = 96).Patients with a central line for administration of PN(n = 63) were identified and details of each CLABSI event were abstracted.We compared the group of patients who experienced CLABSI to the group who did not,to determine whether demographic,clinical,or laboratory factors correlated with development of CLABSI.RESULTS Nineteen of 63 patients(30%,95%CI:19,43) experienced 29 episodes of CLABSI during 4800 line days(6.04 CLABSI per 1000 line days).CLABSI was predominantly associated with Gram-negative organisms(14/29 episodes,48%)including Klebsiella spp.,Enterobacter spp.,and Escherichia coli.The sole polymicrobial infection grew Enterobacter cloacae and Klebsiella pneumoniae.Grampositive organisms(all Staphylococcus spp.) and fungus(all Candida spp.)comprised 9/29(31%) and 6/29(21%) episodes,respectively.No demographic,clinical,or laboratory factors were significantly associated with an increased risk for the first CLABSI event in Cox proportional hazards regression analysis CONCLUSION There is substantial risk for CLABSI among children with BA listed for liver transplantation.No clinical,demographic,or laboratory factor we tested emerged as an independent predictor of CLABSI.While our data did not show an impact of CLABSI on the short-term clinical outcome,it would seem prudent to implement CLABSI reduction strategies in this population to the extent that each CLABSI event represents potentially preventable hospitalization,unnecessary healthcare dollar expenditures,and may exact an opportunity cost,in terms of missed allograft offers.     

Prediction of additional axillary metastasis of breast cancer following sentinel lymph node surgery

Sentinel lymphadenectomy is a sensitive and specific procedure that has reduced the need for complete axillary lymph node dissections in patients with negative sentinel lymph nodes (SLNs). However, numerous studies have shown that SLN may be the only positive lymph node in 40 to 70% of cases. This study was therefore undertaken to determine if the characteristics of primary breast tumor or its metastasis in the SLN could predict the presence of residual disease in the nonsentinel lymph nodes (NSLNs) and thus allow for further reduction in axillary lymph node surgery. The SLN procedure was performed on 329 patients at our institution, of which 131 had positive SLNs and underwent further axillary surgery. Fifty-four patients had additional disease in the NSLNs, while in the remaining 77 cases, no residual disease was detected. The clinical and pathologic features of these cases were reviewed and statistical analysis was performed. Multivariate analysis determined two significant independent variables for prediction of residual disease in the axilla: the size of the metastatic tumor in SLNs and the presence of its extranodal extension. The mean tumor size in SLNs without residual disease in NSLNs was 0.4 cm. It was 1.1 cm in patients with additional NSLN metastasis. The positive predictive value in both instances is about 80%. The risk of NSLN involvement in patients with SLN tumors of < or = 0.4 cm was 21%. The risk was the same (21%) for patients with micrometastatic disease (< or = 0.2 cm) in SLNs. In these cases the residual disease in the NSLNs was also small. SLNs with metastatic deposits larger than 1.0 cm were likely to contain additional metastases in the NSLNs in 81% of cases. This increased to 100% if the primary carcinoma was larger than 5 cm, if it was poorly differentiated, or if it showed HER-2/neu gene amplification. The presence of an extranodal extension of SLN metastasis was an independent predictor of residual axillary disease and was associated with NSLN metastasis in 76% of cases. Primary tumor characteristics did not correlate with the incidence of NSLN metastasis in our series.     

Ophthalmic features and management outcomes of 30 children having Goldenhar syndrome

To study the ophthalmic clinical profile and the management outcomes of children having Goldenhar syndrome (GS). Retrospective review of included children     

Changes in content of triterpenoids and polysaccharides in <Emphasis Type="Italic">Ganoderma lingzhi</Emphasis> at different growth stages

Ganoderma lingzhi is a traditional medicinal mushroom, and its extract contains many bioactive compounds. Triterpenoids and polysaccharides are the primary bioactive components that contribute to its medicinal properties. In this study, we quantified 18 triterpenoids, total triterpenoid content and total polysaccharide content in the ethanol and water extracts of G. lingzhi at different growth stages. Triterpenoids were quantified by liquid chromatograph–tandem mass spectrometry in the multiple-reaction-monitoring mode. Total triterpenoid and total polysaccharide content were determined by colorimetric analysis. The results indicated that the fruit bodies at an early growth stage had a higher content of ganoderic acid A, C2, I and LM2, as well as of ganoderenic acid C and D, than those at a later growth stage. In contrast, ganoderic acid K, TN and T–Q contents were higher in mature fruit bodies (maturation stage). The highest total triterpenoid and total polysaccharide contents were found in fruit bodies before maturity (stipe elongation stage or early stage of pileus formation). Our results provide information which will contribute to the establishment of an efficient cultivation system for G. lingzhi with a higher content of triterpenoids.