Chemically modified carbon-based electrodes for the determination of paracetamol in drugs and biological samples

Paracetamol is a non-steroidal, anti-inflammatory drug widely used in pharmaceutical applications for its sturdy, antipyretic and analgesic action. However, an overdose of paracetamol can cause fulminant hepatic necrosis and other toxic effects. Thus, the development of advantageous analytical tools to detect and determine paracetamol is required. Due to simplicity, higher sensitivity and selectivity as well as costefficiency, electrochemical sensors were fully investigated in last decades. This review describes the advancements made in the development of electrochemical sensors for the paracetamol detection and quantification in pharmaceutical and biological samples. The progress made in electrochemical sensors for the selective detection of paracetamol in the last 10 years was examined, with a special focus on highly innovative features introduced by nanotechnology. As the literature is rather extensive, we tried to simplify this work by summarizing and grouping electrochemical sensors according to the by which manner their substrates were chemically modified and the analytical performances obtained.     

Interaction between capecitabine and gemcitabine with warfarin in a patient with pancreatic cancer

Gemcitabine is the only chemotherapeutic agent approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced pancreatic cancer. 5-fluorouracil or its oral pro-drug, capecitabine is the second most commonly used agent in this malignancy. Capecitabine or 5-fluorouracil is the second most common agent used either in second-line or as a radiosensitizer. Thromboembolism requiring anticoagulation is a common paraneoplastic complication in these patients. We report a patient with pancreatic cancer, challenged with maintaining the international normalized ratio (INR) with gemcitabine-capecitabine combination, and later with gemcitabine monotherapy with concomitant warfarin, as well as, a brief review of the literature. Patients with pancreatic cancer who receive warfarin and gemcitabine should be monitored for any potential drug interactions. Frequent prothrombin time and INR evaluations are suggested for anticoagulated patients receiving gemcitabine, especially when combined with capecitabine.     

Acquired resistance to trimethoprim-sulfamethoxazole during Whipple disease and expression of the causative target gene

BACKGROUND: Whipple disease is a chronic infection caused by Tropheryma whipplei. Trimethoprim-sulfamethoxazole is recommended for treatment of Whipple disease but is associated with treatment failure. T. whipplei is resistant in vitro to trimethoprim, because the gene targeted by this agent is missing. METHODS: A patient experienced clinical failure during treatment with trimethoprim-sulfamethoxazole. The gene encoding the enzyme putatively believed to be dihydropteroate synthase (DHPS), the target of sulfamethoxazole, was amplified and sequenced for 20 T. whipplei strains from our laboratory and for isolates recovered from a case patient at the time of diagnosis and the time of treatment failure. An Escherichia coli knockout strain for this gene was complemented with the sequences from a susceptible strain and from isolates recovered from the case patient. Susceptibilities of complemented E. coli to sulfamethoxazole were tested. RESULTS: The target gene was identified among genes encoding a unique trifunctional enzyme in which DHPS is combined with the 2 preceding enzymes of the folate biosynthesis pathway. Changes in the amino acid sequence of putative DHPS were detected in the case patient. Gene complementation showed that the gene encoding putative DHPS restored the folate biosynthesis pathway and susceptibility to sulfamethoxazole, whereas the mutated sequence was associated with sulfamethoxazole resistance. CONCLUSIONS: Antibiotic susceptibility of fastidious bacteria such as T. whipplei can be evaluated by means of gene complementation techniques. Mutations in the target gene of sulfamethoxazole appear during treatment.     

The many faces of peroxisomal disorders: Lessons from a large Arab cohort

Defects in the peroxisomes biogenesis and/or function result in peroxisomal disorders. In this study, we describe the largest Arab cohort to date (72 families) of clinically, biochemically and molecularly characterized patients with peroxisomal disorders. At the molecular level, we identified 43 disease-causing variants, half of which are novel. The founder nature of many of the variants allowed us to calculate the minimum disease burden for these disorders in our population ~1:30 000, which is much higher than previous estimates in other populations. Clinically, we found an interesting trend toward genotype/phenotype correlation in terms of long-term survival. Nearly half (40/75) of our peroxisomal disorders patients had documented survival beyond 1 year of age. Most unusual among the long-term survivors was a multiplex family in which the affected members presented as adults with non-specific intellectual disability and epilepsy. Other unusual presentations included the very recently described peroxisomal fatty acyl-CoA reductase 1 disorder as well as CRD, spastic paraparesis, white matter (CRSPW) syndrome. We conclude that peroxisomal disorders are highly heterogeneous in their clinical presentation. Our data also confirm the demonstration that milder forms of Zellweger spectrum disorders cannot be ruled out by the “gold standard” very long chain fatty acids assay, which highlights the value of a genomics-first approach in these cases.     

Safety and outcome using endoscopic dilatation for benign esophageal stricture without fluoroscopy

AIM:To investigate the use of Savary-Gilliard marked dilators in tight esophageal strictures without fluoros-copy. METHODS:Seventy-two patients with signif icant dysphagia from benign strictures due to a variety of causes were dilated endoscopically. Patients with achalasia, malignant lesions or external compression were excluded. The procedure consisted of two parts. First, a guide wire was placed through video endoscopy and then dilatation was performed without fluoroscopy. In general, "the rule of three" was followed. Effective treatment was defi ned as the ability of patients, with or without repeated dilatations, to maintain a solid or semisolid diet for more than12mo. RESULTS: Six hundred and sixty two dilatations in a total of72patients were carried out. The success rate for placement of a guide wire was100%and for dilatation97%,without use of fluoroscopy, after6mo to4years of follow-up.The number of sessions per patient was between1and7,with an average of2sessions.The ability of patients, after 1 or more sessions of dilatation, to maintain a solid or semisolid diet for more than 12mo was obtained in70patients(95.8%).For very tight esophageal strictures, all patients improved clinically without complications after the endoscopic procedure without fluoroscopy, but we noted3failures. CONCLUSION:Dilatation using Savary-Gilliard dilators without fluoroscopy is safe and effective in the treatment of very tight esophageal strictures if performed with care.