Methamphetamine abuse and “meth mouth” in Europe

With easy chemical synthesis from its precursor, methamphetamine (MA) is now widespread in many countries. The abuse of methamphetamine is associated with several negative effects on health, because MA is a neurotoxin and a dangerous central nervous system stimulant. It changes levels of neurotransmitters in the brain, releasing dopamine and inhibiting nor epinephrine uptake which increases sympathetic nervous system activity and can lead to cardiac arrhythmia, hypertension and tachypnea. The consequences of MA abuse are clearly manifested in oral diseases (like “meth mouth”) which is characterised by extensive caries, teeth grinding with ensuing dental wear and trismus. The present review was designed to fill the gap in knowledge about methamphetamine abuse in the European Union (EU) and to illustrate the main clinical effects of prolonged use. After describing the pharmacology and systemic effects of methamphetamine and concentrating on its effects on the mouth, the present review compares the epidemiology and incidence of abuse in the world, particularly the USA and the EU. Key words:Methamphetamine, “Meth mouth”, drug abuse, oral health.     

Case report: a patient with Hodgkin's disease after treatment for testicular cancer.

A young patient developed Hodgkin's disease 11 years after surgical, chemotherapeutic and radiation treatment for stage IIIA embryonal carcinoma of the testis. The importance is stressed of establishing a tissue diagnosis when there is an unexpected course of the disease.     

Structure-activity relationship between (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil (BV-araU, V-araU) in inhibition of Epstein-Barr virus replication.

The structure-activity relationship between (E)-5-(2-bromovinyl)- and 5-vinyl-1-beta-D-arabinofuranosyluracil (BV-araU and V-araU) in inhibition of Epstein-Barr virus (EBV) was evaluated. Both V-araU and BV-araU effectively inhibited EBV replication in virus-producer P3HR-1(LS) cells, as determined by DNA-DNA hybridization. The 50% effective doses (ED50) for viral DNA replication were 0.005 and 0.3 microM for V-araU and BV-araU, respectively. The in vitro therapeutic index was 4000 for V-araU and 1300 for BV-araU. Synthesis of EBV-induced polypeptides with molecular weights of 145,000 (145, 140, 130, and 110 kDa) was significantly inhibited by both drugs. Only V-araU inhibited the synthesis of 85-, 55-, and 32-kDa polypeptides by approx. 50%. Kinetic analysis of inhibition and reversibility of EBV DNA replication after removal of the drugs indicated that BV-araU has a more prolonged inhibitory effect than V-araU. These results indicate that the substitution of H by Br in the 5-vinyl group results in marked reduction in anti-EBV activity while prolonging the drug effect and diminishing cytotoxicity.     

Operative laparoscopy for uterine pathology.

In the first years of its use, operative laparoscopy for uterine pathology was employed in the surgical treatment of myomas and in the correction of uterine retroversion (hysteropexy). More recently the technique has been employed for the laparoscopically assisted hysterectomy or for subtotal laparoscopical hysterectomy using the Semm Kit. Also radical hysterectomy has been performed in advanced centers by laparoscopy. In this paper, the Authors discuss the indications, the counterindications, the risks and complications of the operative laparoscopy in the different forms of ovarian pathology.     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.     

Urinary excretion of glycated albumin in insulin-dependent diabetic patients with micro- and macroalbuminuria.

Non-enzymatic glycosylation (glycation) involves both circulating proteins, such as albumin and structural proteins, such as the components of the glomerular basement membrane. Glycated albumin is more anionic than unmodified plasma albumin at physiologic pH. Preferential urinary excretion of glycated proteins has occasionally been reported in diabetes. We therefore investigated the selectivity index (renal clearance of non-glycated/glycated albumin) in 25 insulin-dependent diabetic patients (17 with microalbuminuria and 8 with macroalbuminuria), and 19 healthy subjects. The selectivity index was significantly higher (p less than 0.01) in the microalbuminuric patients than in the macroalbuminuric patients and the control subjects: 1.11 +/- 0.03 SEM vs 0.94 +/- 0.08 vs 0.98 +/- 0.02. These results are not consistent with preferential urinary excretion of glycated albumin in insulin-dependent diabetic patients with increased urinary albumin excretion.     

Glutathione mutagenesis in Salmonella typhimurium is a {gamma}-glutamyltranspeptidase-enhanced process involving active oxygen species

Reduced glutathione (GSH) is mutagenic in Salmonella in thepresence of -glutamyltranspeptidase (GGT), with the highestresponse obtained in strain TA102. Reduced cysteinylglycine,one of the products of GGT metabolism of GSH, is mutagenic inthe absence of GGT. In strain TA102, GSH mutagenesis was dependenton molecular oxygen, enhanced by iron, inhibited by EDTA, desferrioxaminemesylate, mannitol, butylated hydroxyanisole, peroxidase andcatalase, but not by superoxide dismutase. Binding of GSH orits GGT-dependent metabolites to DNA in vitro was not detected.This is consistent with a model of an indirect mechanism ofmutagenesis, i.e. cleavage of GSH by GGT, followed by facileauto-oxidation of the resulting cysteinylglycine, with the productionof free radicals which lead to the (pen)ultimate mutagen, H₂O₂.