Post sclerotherapy esophageal ulcers: a prospective analysis of their behaviour

The reported incidence of post sclerotherapy esophageal ulcers has shown marked variation, possibly due to lack of uniform criteria for their diagnosis. Using fixed criteria (size greater than or equal to 5 mm, duration greater than or equal to 2 weeks), we prospectively studied 82 patients with portal hypertension, who underwent four or more sessions of endoscopic sclerotherapy (EST), for the occurrence and behaviour of these ulcers. Post sclerotherapy ulcers occurred after 43 (9.2%) of 465 EST sessions in 30 (36.6%) of 82 patients. Ulcers were significantly associated with two complications: rebleed during the course of sclerotherapy (33% of ulcers bled compared to 3% from variceal rupture; p less than 0.001) and esophageal stricture formation (66.7% of strictures occurred in patients who had ulcers; p less than 0.05). Ulcers occurred more frequently in patients with poor liver function (61.5% in Child's C grade compared with 31.9% in Child's A or B grades; p less than 0.05) and after injection into larger varices (83.7% in varices grades 3 and 4, 16.3% in lower grades; p less than 0.005). Severe persistent chest pain (p less than 0.001) and pyrexia (p less than 0.01) after sclerotherapy were clinical pointers of ulcerogenesis.     

Toxicity of 1-phenylcyclohexene and its interaction with phencyclidine

The toxicity of 1-phenylcyclohexene (PC), a pyrolysis product of phencyclidine (PCP), and its interaction with PCP were evaluated. The ip LD50 of PC in Swiss male mice was 22 mmol/kg. Treatment of mice with PC at 2.2 mmol/kg/day, ip, for up to 7 days increased the liver/body weight ratio, which returned to normal within 7 days after PC withdrawal. Increases of 32% in serum glutamic-oxalacetic transaminase (SGOT) and 94% in serum glutamic-pyruvic transaminase (SGPT) were observed within 4 hr following the initial (Day 1) dose of PC. Smaller increases in the SGOT activity continued following Day 2 and 3 PC administrations. The SGPT activity remained elevated after these treatments. Activities of both enzymes, however, returned to normal within 24 hr following daily PC injections. No pathologic changes were observed in liver, brain, spleen, kidneys, and lungs with light microscopy. PC treatment for 4 days at 2.2 or 4.4 mmol/kg produced proliferation along with dilatation and fragmentation of the endoplasmic reticulum in liver. Scattering of ribosomes in the cytoplasm and dilatation of rough-surfaced cisternae were prominent at the higher dosage. Pretreatment of animals for 4 days with PC (1.1, 2.2, and 4.4 mmol/kg, ip) decreased pentobarbital- (60 mg/kg) induced sleeping time by 27, 64, and 80% and lowered PCP- (16.4 mumol/kg) stimulated locomotor activity by 18, 28, and 41%, respectively. Pretreatment of animals with PC for 1 hr inhibited (ED50: 2.3 mmol/kg) the PCP-induced locomotion. These results indicate that the PC treatment during a 7-day period produces some undesirable effects on liver function, which are reversible on its discontinuation. However, PC also weakens toxic effects of PCP.     

In vitro degradation of apo-, zinc-, and cadmium-metallothionein by cathepsins B, C, and D.

Metallothionein (MT) has been extensively studied over the past several years because of its probable role in endogenous metal homeostasis and cellular protection. A large body of knowledge now exists describing the physicochemical properties of MT as well as the mechanisms involved in MT induction. It has been well established that MT protects tissues from metal toxicity by chelating metals that would otherwise be available to interact with and disrupt vital cell functions. Information on the degradation of metal-saturated MT and the fate of the metals associated with it would be extremely important in predicting metal toxicity. Lysosomes have been targeted as a possible subcellular site for the turnover of MT; however, the susceptibility of MT to degradation by specific acidic proteases (i.e., cathepsins) has not been described. Therefore, the purpose of the present study was to examine the relative abilities of cathepsins B, C, and D to degrade Zn7-MT, Cd7-MT, and apo-MT in vitro. In so doing, the effects of metal species, degree of metal saturation, and pH on the degradation processes were evaluated. Time course experiments revealed that apo-MT was rapidly degraded by all three cathepsins. Cathepsin B degraded apo-MT approximately 36-fold more rapidly than cathepsin C and 45-fold more rapidly than cathepsin D. Therefore, under the in vitro conditions used in this study, the relative potency of the cathepsins tested was cathepsin B much much greater than cathepsin C greater than cathepsin D. In comparison, metal-saturated MT was more than 1000-fold more resistant to degradation by the cathepsins tested. In order to determine how much metal was needed to protect MT against degradation, apo-MT was reconstituted with increasing molar equivalents of Zn2+. The results suggest that as metal to apo-MT ratios increase, less apo-MT substrate is available to the protease and degradation decreases.     

1(2-Benzoylethyl)pyridinium chloride: A new potent and selective inhibitor of bovine brain and human placental choline acetyltransferase

A newly synthesized 1(2-benzoylethyl)pyridinium (BEP), an analog of the choline acetyltransferase (ChA) inhibitor (2-benzoylethyl)trimethylammonium (BETA), was evaluated for its ability to inhibit ChA from bovine brain and human placenta. Its ChA inhibitory properties were compared with that of BETA. BEP was found to be an effective inhibitor of ChA (I50: 10-18 microM). BEP, as well as BETA, was a linear noncompetitive inhibitor of ChA with respect to both substrates, acetylcoenzyme A and choline. BEP and BETA were poor inhibitors of electric eel acetylcholinesterase. These observations indicate that BEP is a potent and selective inhibitor of ChA. Furthermore, because of the possible delocalization of the positive charge at the N atom of the BEP molecule throughout the pyridine ring, it is anticipated that BEP would have a higher potential for lipid solubility, stability and selectivity than BETA.     

Inadvertent duodenal stenting: a case report.

A Gianturco type metallic stent placed in the common bile duct migrated into the duodenum. The device remains in situ, and has caused no ill-effects to date. This raises the possibility that such stents may be deployed in the gastrointestinal tract.     

Dermatomycosis in Goats in India

Summary: In an extensive survey involving 2176 goats 1.56% of goats manifested clinical lesions of ringworm infection. Animals below the age of 6 months were affected most (4.20%). The incidence of infection was higher during the winter months. T. verrucosum, T. mentagrophytes and M. gypseum were isolated from the skin scrapings of 12, 4, and 2 goats respectively. It is suggested that the infected animals could be a source of disease to human population in which the zoophilic dermatophyte invasion is characterized by severe inflammatory lesions of the skin. The zoonotic importance of different dermatophytes is stressed.
Zusammenfassung: In einer ausgedehnten Untersuchung an 2176 Ziegen wurden bei 1,56% klinische Zeichen einer Hautmykose festgestellt. Tiere, die jühger als 6 Monate alt waren, zeigten mit 4,20% am häfigsten Krankheitssymptome. In den Wintermonaten war die Erkrankungshäufigkeit am gröBten. T. vermcosum, T. mentagrophytes and M. gypseum wurden jeweils von 12,4 bzw. 2 Ziegen isoliert. Die inflzierten Tiere köinnen eine Infektionsquelle für die menschliche Bevölkerung darstellen und dort Mykosen mit stark entzündlichen Veränderungen auslösen. Die Bedeutung verschiedener Dermatophyten als Erreger von Zoonosen wird hervorgehoben.     

Investigations on the toxicological profile of functionalized fifth-generation poly (propylene imine) dendrimer

Dendrimers have generated tremendous interest in the field of drug delivery. Despite indications of their utility as drug carriers, the inherent cytotoxicity associated with polycationic dendrimers acts as a limiting factor to their clinical applications. Many functionalization strategies have been adopted to mask peripheral amines in order to overcome this limitation. The object of the present investigation was to evaluate the effect of functionalization on the toxicological profile of fifth-generation poly(propylene imine) dendrimer (PPI-5.0G). Four forms of functionalized dendrimers, including protected glycine and phenylalanine, and mannose and lactose functionalized poly(propylene imine) (PPI) dendrimer, were synthesized as prospective drug carriers. These dendrimeric systems were evaluated for haemolytic toxicity, cytotoxicity, immunogenicity and haematological parameters. PPI-5.0G demonstrated a positive charge-based time- and concentration-dependent toxicity profile. Functionalization greatly improved the toxicity profile of the parent dendrimer. Hence it is proposed that these functionalized forms of PPI dendrimer have great potential as bio-compatible drug vehicles.     

Functional polymeric nanoparticles: an efficient and promising tool for active delivery of bioactives

Nanotechnology is a multidisciplinary field and has achieved breakthroughs in bioengineering, molecular biology, diagnostics, and therapeutics. A recent advance in nanotechnology is the development of a functional nanosystem by incorporation, adsorption, or covalent coupling of polymers, carbohydrates, endogenous substances/ligands, peptides, proteins, nucleic acids, and polysaccharides to the surface of nanoparticles. Functionalization confers a wide array of interesting properties such as stealth characteristics, a bioadhesive property, and that it prevents aggregation of nanoparticles, imparts biostability and solubility, reduces toxicity, and provides site-specific delivery. This makes the nanosystem an intelligent tool for diagnostics, prognostics, and controlled and sustained delivery of protein, peptide, pDNA, and other therapeutic agents to specific targets (tissue, cell, and intracellular). Various types of functional nanosystems, such as carbon nanotubes, quantum dots, polymeric micelles, dendrimers, metallic nanoparticles, and liposomes, are being extensively explored. However, high tissue accumulation of nonbiodegradable nanoparticles has caused toxicity problems and rendered them as not-so-popular therapeutic and diagnostic systems. The toxicity and safety of nonbiodegradable nanoparticles are subject to future research. Polymeric nanoparticles have offered attractive alternative modules due to biocompatibility, nonimmunogenicity, nontoxicity, biodegradability, simple preparation methods, high physical stability, possibility of sustained drug release, and higher probability for surface functionalization. Depending on properties that have been modified, polymeric nanoparticles can be grouped in to four classes, namely, stealth, polysaccharide decorated biomimetic, bioadhesive, and ligand-anchored functional polymeric nanoparticles (f-PNPs). This review explores the ligand-anchored f-PNP as a carrier for active delivery of bioactives, envisaged to date. This review also details the ligands available for conjugation, their method of coupling to nanoparticles, and applications of f-PNPs in anticancer drug delivery, oral delivery, gene delivery, vaccine delivery, and intracellular delivery; site-specific delivery to liver, macrophages, lymphatics, and brain; and miscellaneous applications. This review also addresses formidable challenges encountered, and proposes some future strategies for development of a promising site-specific active delivery system.