Fluorine-thiol displacement probes for acetaminophen's hepatotoxicity

Chemicals possessing reactive electrophiles can denature innate proteins leading to undesired toxicity, and the overdose-induced liver injury by drugs containing electrophiles has been one of the major causes of non-approval and withdraw by the US Food and Drug Administration (FDA). Elucidating the associated proteins could guide the future development of therapeutics to circumvent these drugs' toxicities, but was largely limited by the current probing tools due to the steric hindrance of chemical tags including the common "click chemistry" labels. Taking the widely used non-steroidal anti-inflammatory drug acetaminophen (APAP) as an example, we hereby designed and synthesized an APAP analogue using fluorine as a steric-free label. Cell toxicity studies indicated our analogue has similar activity to the parent drug. This analogue was applied to the mouse hepatocellular proteome together with the corresponding desthiobiotin-SH probe for subsequent fluorine-thiol displacement reactions (FTDRs). This set of probes has enabled the labeling and pull-down of hepatocellular target proteins of the APAP metabolite as validated by Western blotting. Our preliminary validation results supported the interaction of APAP with the thioredoxin protein, which is an important redox protein for normal liver function. These results demonstrated that our probes confer minimal steric perturbation and mimic the compounds of interest, allowing for global profiling of interacting proteins. The fluorine-thiol displacement probing system could emerge as a powerful tool to enable the investigation of drug-protein interactions in complex biological environments.

The proportion of fevers attributable to malaria varies significantly between sites in Papua New Guinea

@#Malaria is endemic across lowland Papua New Guinea (PNG) and case management has been based on symptomatic diagnosis and presumptive treatment of fever cases with an antimalarial. This study aimed to investigate the prevalence of malaria infection among fever cases presenting to 5 purposely selected sentinel health facilities in order to estimate the proportion of patients requiring antimalarial drugs. A total of 1807 fever patients were screened. Overall, 45% of fever patients had a positive malaria blood slide; 35% were infected with Plasmodium falciparum, 9% with P. vivax and 2% with P. malariae. Slide positivity was highest in Dreikikir (75%) and lowest in Wipim (2%). Among patients aged 1-4 years, 22% had moderate to severe anaemia (Hb < 8 g/dI) and 21% of children 2-9 years of age showed signs of splenomegaly (Hackett score 1-5). Comorbidity differed significantly between study sites and was not closely correlated with malaria infection. Clinical diagnosis by health facility staff was malaria for 67% of all fever cases, including 89% of slide-positive and 48% of slide-negative patients. 70% of rapid diagnostic test-negative cases were treated with an antimalarial. It is estimated that due to the lack of parasitological diagnosis the selected health facilities reported an excess of 18% (Dreikikir) to 98% (Wipim) malaria patients on average each month. In consideration of the significant differences in malaria-attributable fevers between study sites, the implementation of parasitological diagnosis in health facilities and administration of antimalarials only to test-positive patients has the potential to significantly improve the management of fever cases and reporting of malaria. A better tailoring to different settings may increase the effectiveness of malaria control interventions.

Utilisation of public eye care services by the rural community residents in the Capricorn district, Limpopo Province, South Africa

Background: Visual impairment and blindness are major health problems worldwide; especially in the rural and remote areas of developing countries. Utilisation of eye care services is essential to reduce the burden of visual impairment and blindness; and it is therefore important that it is monitored. Objectives: The objectives of this study were to determine the level of utilisation of publiceye care services and factors that might have influenced their usage in rural communities; Capricorn district; Limpopo Province; South Africa. Method: A population-based cross-sectional study design was used. Participants were residents in selected rural villages located within approximately 5 km of six Government hospitals. Following ethical approval and receipt of informed consent; a questionnaire with closed and open-ended questions was used to collect information on the utilisation of eye care services and factors that might influence utilisation. Descriptive statistics and Pearson's Chisquare test were used to analyse and compare the data. Results: Many (62.7) of the respondents had used the government eye care services in the past. Over fifty-nine per cent (59.3) of them were satisfied with the services. Factors reported to influence utilisation (such as monthly income; knowledge of available services and the need for regular eye tests) were positively associated with utilisation of eye care services in this study (p 0.05). Conclusion: Utilisation of eye care services was relatively good; but varied significantly between sites. An awareness campaign by government and non-governmental organisations about eye care services may increase utilisation amongst rural communities

Comportamento de componentes bioquímicos do sangue em equinos submetidos à ozonioterapia / Profile of blood biochemistry components in horses treated with ozone therapy

O comportamento de constituintes bioquímicos sanguíneos (glicose, fibrinogênio, creatina fosfoquinase e gama-glutamiltransferase) foi monitorado, in vivo, em 12 equinos mestiços (seis machos e seis fêmeas), com idade entre 4 e 20 anos, submetidos à ozonioterapia. O tratamento foi realizado mediante administração de 500 ou 1000mL da mistura de oxigênio-ozônio (O2-O3) por via intravenosa, a cada três dias, durante 24 dias. Os equinos foram distribuídos em quatro grupos: MT500 constituído por três machos tratados com 500mL; MT1000 por três machos tratados com 1000mL; FT500, por três fêmeas tratadas com 500mL e FT1000, por três fêmeas tratadas com 1000mL. A ozonioterapia por via intravenosa não ocasionou alterações clínicas nos equinos. Os valores médios mínimos e máximos de glicose, fibrinogênio, creatina fosfoquinase e gama-glutamiltransferase mantiveram-se dentro dos limites de referência para a espécie equina. Houve diminuição nas concentrações da glicose e gama-glutamiltransferase ao longo dos períodos de aplicação e aumento nos valores do fibrinogênio. A creatina fosfoquinase não sofreu efeito do tratamento.

The profile of blood biochemistry variables (glucose, fibrinogen, creatine phosphokinase, and gamma glutamyltransferase) was in vivo monitored in 12 crossbred horses (six males and six females), aging from four to 20-years-old treated with ozone therapy. Treatments were carried out by applying 500 or 1000mL of the mixture oxygen-ozone (O2-O3) via intravenous route, every three days, during 24 days. Horses were assigned to four groups: MT500 (three males given 500mL), MT1000 (three males given 1000mL), FT500 (three females given 500mL) and FT1000 (three females given 1000mL). Ozone therapy by intravenous route caused no clinical changes in the horses. Minimum and maximum mean values of glucose, fibrinogen, creatine phosphokinase, and gamma glutamyltransferase were within the range considered as normal reference for the equine species. There was decrease in glucose and gamma glutamyltransferase concentrations over the period of application, whereas fibrinogen increased and creatine phosphokinase was not affected by the treatment.

Optical internal urethrotomy

During a 20 month period, 38 patients with urethral strictures were treated by Optical Internal urethrotomy at East Avenue Medical Center. The surgical technique, parameters like etiology, location and length of stricture, and complications of the procedure were described. The overall success rate was 78.9%. Good results were achieved in 25 patients (65%) and satisfactory results were noted in 5 patients (13%). Failure rate was 21% while the complication rate was 18%. Patients with strictures more than 2 cm long had an unsatisfactory outcome. Optical Internal Urethrotomy was determined to be simple and determined to be safe technique that should be considered as an option before definitive urethroplasty.

Comparative study of available fixatives in the preservation of tumor cells from bladder washings

A comparative, single blind study is done on the effect and length of time of preservation of cancer cells from unrefrigerated, barbotaged urinary bladder washings with the use of available fixatives as follows: 10% formalin, 100% methanol, 95% ethanol, 100% methanol + acetone (1:1), 100% methanol + acetic acid (3:1) and 100% methanol + acetic acid (20:1). Fifteen (15) patients with transitional cell CA and two (2) patients with squamous cell CA of the urinary bladder are included in the study. Tumor cells are preserved up to 7 days with the optimum placed at 5 days. Methanol 100% and 100% methanol + acetone (1:1) are recommended as the fixative of choice.

Simultaneous bilateral percutaneous nephrolithotripsy

From July 1987 to May 1990, a total of 13 simultaneous bilateral percutaneous nephrolithotripsies (PCNL) were performed in two medical institutions for bilateral proximal ureteral stones, bilateral pelvolithiasis and nephrolithiasis, and bilateral staghorn calculi. No major complications occurred. It appears that simultaneous bilateral PCNL has several advantages including reasonable operative time, safety of the procedure and cost effectiveness. Greater applications of this procedures is encouraged. (Author)