An unusual cause of macular infarction: protein-losing enteropathy

Protein-losing enteropathy is a multisystem disorder characterized by abnormally high loss of plasma proteins in the gastrointestinal tract. In addition to loss of plasma proteins there is also loss of anticoagulant globulins leading to a prothrombotic state in the body. Single case observation. The patient developed unilateral macular infarction with non-embolic cerebral infarct due to loss of Antithrombin 3 and Protein S proteins in the gastrointestinal tract. The patient had poor recovery of vision due to severe ischemic retinal injury. The gastroenterology team should be on an alert to rule out prothrombotic states in such patients to prevent such complications.     

Aldol derivatives of Thioxoimidazolidinones as potential anti-prostate cancer agents

The paper discusses the synthesis and stereochemical aspects of the anti aldol products, 3-(substituted phenyl)-5-[(substituted phenyl) hydroxy methyl]-5-methyl-4-oxo-2-thioxoimidazolidines. The stereochemistry observed in the aldol reactions with benzaldehydes was explained by transition state model of the endocyclic (E)-enolate formed from the rigid 4-oxo-2-thioxoimidazolidine skeleton. Proton NMR and ROESY spectral analyses were carried out to identify the syn and anti conformations of the aldol diastereomers. Configurations of the enantiomers of the representative anti aldol product 3-(4-chlorophenyl)-5-[(4-chlorophenyl) hydroxy methyl]-5-methyl-4-oxo-2-thioxoimidazolidine was determined by single crystal XRD studies. The compounds were screened in vitro against prostate cancer cell lines, PC-3 and LNCaP and the most potent derivatives were identified.     

Increased risk of hepatitis E in sewage workers from India

Considering feco-oral transmission of hepatitis E virus (HEV), the risk of the infection was assessed among sewage workers. On the basis of the close contact with sewage, the participants (n = 147) were divided into sewage workers (n = 92) and others (n = 55); none used personal protective equipment (eg, coveralls, boots, gloves) Age-matched individuals from lower socioeconomic status and without any exposure to sewage were used as controls. IgG-anti-HEV positivity in enzyme-linked immunosorbent assay was significantly higher (P < 0.01) among staff members (83/147, 56.5%) than the controls (19%). A significant rise in anti-HEV positivity (P < 0.05) was recorded in sewage workers working for >5 years. Multivariate regression analysis identified contact with sewage as the independent variable associated with anti-HEV positivity. Strict adherence to good working practices must take top priority for protection of these workers from sewage pathogens.     

Performance evaluation of a full-scale coke oven wastewater treatment plant in an integrated steel plant

Wastewater generated during coke-oven gas cleaning operations in the integrated steel plant contains phenol, cyanide, thiocyanate, and also oil and grease. Although the activated sludge process is widely practiced for biological treatment of coke-oven wastewater, it was observed during the evaluation of performance of full scale coke-oven wastewater treatment plant that oil contamination and poor sludge settleability had resulted in poor maintenance of the activated sludge process. Keeping these aspects in view, treatability studies were conducted and an alternative treatment process is proposed. With these corrective measures the coke-oven wastewater treatment plant will give desired performance. In this paper we present results of the performance evaluation, data on treatability studies and alternative treatment process scheme.     

The ABCG2 C421A polymorphism does not affect oral nitrofurantoin pharmacokinetics in healthy Chinese male subjects

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• An increasing number of drugs on the market or under development have been identified as substrates of the ATP-binding cassette drug efflux transporter breast cancer resistance protein (BCRP; ABCG2), which can affect the pharmacokinetics of drugs by reducing absorption and/or increasing biliary elimination.
• ABCG2 C421A, a single nucleotide polymorphism associated with decreased protein expression/transport activity in vitro and higher anti-cancer drug concentrations in carriers of the C421A polymorphism, may contribute to the intersubject pharmacokinetic variability of BCRP substrates.
• Predicting the potential influence of BCRP on drug disposition or drug interactions is challenging because of the lack of a well-characterized, BCRP-selective clinical probe substrate.
• Nitrofurantoin is potentially a suitable clinical BCRP probe substrate based on preclinical and clinical information available (e.g. in vitro transport studies, Bcrp knockout mouse studies, inhibition studies in rats, and milk secretion studies in rats and humans).

WHAT THIS STUDY ADDS

• The ABCG2 C421A SNP had no effect on oral nitrofurantoin plasma and urine pharmacokinetic parameters in healthy male Chinese subjects.
• Nitrofurantoin does not appear to be a useful clinical BCRP probe.

AIMS

A number of drugs are substrates or inhibitors of the efflux transporter breast cancer resistance protein (BCRP; ABCG2), which can limit systemic exposure by reducing absorption and/or increasing biliary elimination. The identification of a BCRP-selective clinical probe drug would provide a useful tool to understand the effect of genetic polymorphisms and transporter-based drug interactions on drug pharmacokinetics. The aim of this study was to assess the utility of nitrofurantoin as a clinical probe substrate for BCRP activity by evaluating the impact of genetic variation on nitrofurantoin pharmacokinetics.

METHODS

Nitrofurantoin pharmacokinetics were studied in an open-label, single-oral dose (100 mg) study in 36 male Chinese subjects who were pre-screened for ABCG2 421 CC, CA and AA genotypes (n = 12 each). Plasma and urine concentrations of nitrofurantoin were determined by LC/MS/MS and LC/UV respectively. anova was used to compare pharmacokinetic parameters among genotypes.

RESULTS

There were no significant differences in nitrofurantoin pharmacokinetics among the genotypic cohorts. The geometric mean nitrofurantoin plasma AUC_(0-∞) (95% confidence interval) values were 2.21 (2.00, 2.45), 2.42 (2.11, 2.78) and 2.32 (1.99, 2.70) µg h ml⁻¹ and half-life values were 0.79 (0.59, 1.0), 0.76 (0.64, 0.89) and 0.72 (0.62, 0.84) h for ABCG2 421 genotypes CC, CA and AA, respectively. The percentage of dose excreted unchanged in the urine was 43, 44 and 39%, respectively.

CONCLUSIONS

The ABCG2 C421A polymorphism had no effect on nitrofurantoin plasma and urine pharmacokinetic parameters in healthy Chinese subjects. These results indicate that nitrofurantoin is not a suitable clinical probe substrate for assessing BCRP activity.     

Studies on synthesis and pharmacological activities of 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazoles and their dihydro analogues

Several 3,6-disubstituted-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole and their dihydro analogues were synthesized from hetero aromatic acids and hetero aromatic aldehydes, respectively, by microwave-assisted dry media and conventional methods. Elemental analysis, IR, (1)H NMR, (13)C NMR and mass spectral data elucidated the structures of all newly synthesized compounds. Synthesized compounds are studied for their antibacterial, antifungal, anti-inflammatory and analgesic activities. Some of the tested compounds showed significant pharmacological activities.     

Technik der biologischen Osteosynthese von subtrochantären Frakturen mit der dynamischen Kondylenschraube (DCS)

Zusammenfassung Operationsziel Behandlung geschlossener subtrochantärer Mehrfragmentfrakturen mit der dynamischen Kondylenschraube (DCS) mit dem Ziel der Verkürzung der Operationszeit sowie der Verringerung des Blutverlusts und der Rate von verzögerten Bruchheilungen. Indikationen Subtrochantäre Mehrfragmentbrüche, besonders solche der Typen B und C nach der AO-Klassifikation. Frakturen, die bis in die Fossa pyramidalis hineinreichen und für eine intramedulläre Stabilisierung nicht geeignet sind. Schlechter Allgemeinzustand, der keine längere Narkosen zulässt, wie sie u. U. bei der Marknagelung benötigt wird. Kontraindikationen Offene Frakturen. Übergewichtigkeit. Frakturen des Calcar femoris sind keine Kontraindikation! Operationstechnik Zugang entweder über kleine Inzisionen proximal und distal oder über einen verkürzten Standardzugang ohne Eröffnung der Trümmerzone der Fraktur und zum Erhalt des Frakturhämatoms. Die DCS wird unter Bildwandlerkontrolle eingebracht. Die Platte wird unter dem Musculus vastus lateralis durchgeschoben und am Schluss um 180° gedreht, damit die Führungshülse über die DCS gleiten kann. Die Position wird in drei Ebenen radiologisch überprüft. Proximal und distal der Frakturzone wird die Platte mit Schrauben fixiert. Ergebnisse Zwischen 10/1995 und 02/1999 wurden 28 Männer und drei Frauen mit subtrochantären Frakturen mit einer DCS nach biologischen Prinzipien operiert. Knöcherne Ausheilung wurde bei allen 31 Patienten erreicht. Vollbelastung war nach durchschnittlich 4,9 Monaten möglich. Die durchschnittliche Operationszeit betrug 2 h, der durchschnittliche Blutverlust 430 ml. Ein Patient erlitt eine oberflächliche Infektion, die nach Débridement und Antibiotikatherapie ausheilte. Fehlstellungen wurden zweimal beobachtet; sie bedurften keiner Korrektur. Die Ergebnisse sind im Hinblick auf den Blutverlust, die Operationszeit und die Heilungsquote besser als diejenigen mit offener Operationstechnik. Abstract Objective Treatment of closed comminuted subtrochanteric fractures using the dynamic condylar screw (DCS), with the goal of reducing operating time, blood loss, and incidence of delayed union. Indications Comminuted subtrochanteric fractures, especially types B and C of the AO classification. Fracture line extending to piriformis fossa precluding use of an intramedullary device. Poor general condition, i. e., unable to withstand prolonged anesthesia as required in open reduction and internal fixation (ORIF)/nailing. Contraindications Compound fractures. Obesity. Calcar comminution is not a contraindication! Surgical Technique Approach either through small proximal and distal incisions or limited exposure of the fracture site without opening the region of comminution and preservation of medial fracture hematoma. DCS inserted under image intensifier control. Plate slid beneath vastus lateralis. Rotated 180° to allow barrel to slice over condylar screw. Alignment in all three planes confirmed under radiologic control. Proximal and distal screws inserted to stabilize the fracture. Results Between 10/1995 and 02/1999, 28 men and three women with subtrochanteric fractures were treated with a DCS using biologic principles. Union was achieved in all 31 patients (100%) and full weight bearing possible after an average of 4.9 months. The average operating time was 2 h, and blood loss averaged 430 ml. Only one patient had a superficial infection, which settled on local debridement and antibiotics. Malunion was seen twice (6.4%) which did not require further surgery. These results are superior to open technique in respect to blood loss, surgical time, and union rate.