The health threat of new synthetic opioids as adulterants of classic drugs of abuse.

Extensive scientific evidence shows that there is a broad spectrum of substances used as adulterants, whose effects on the user's health may be extremely harmful. The degree of purity of the drugs most commonly abused is highly variable depending on the region or epidemiological context. Practices of drug adulteration have been substantially evolving over the years: a significant trend has been observed in the last decade indicating a decline in the average purity of most drugs. Although the most frequent adulterants of common street drugs have long been well known, the rise of synthetic opioids has inevitably entailed gaps in knowledge in terms of the substances being used and their composition, which constitutes an even greater threat to public health.

The health threat of drugs of abuse adulteration by new psychoactive substances.

The practice of drug of abuse adulteration is changing. Currently, the risk of new adulteration practices involves New Psychoactive Substances (NPS), which can also be used as adulterants. In particular, the phenomenon of adulteration concerns fentanyl and its analogs, substances that can be toxic even if taken in very small quantities. The adulteration that involves NPS is creating a serious threat to the health of drug users, not only because of the pharmacological action but because of the increased toxicity of these new cutting agents.

Sildenafil-associated hepatoxicity: a review of the literature.

Sildenafil citrate (Viagra®) is a vasoactive agent available worldwide since 1998 for the treatment of male erectile dysfunction. It is a selective phosphodiesterase type 5-enzyme inhibitor able to potentiate the downstream effects of nitric oxide on smooth muscle relaxation and vasodilation through its effects on the cyclic guanosine monophosphate (c-GMP) pathway in the erectile tissue of the penis. When sildenafil is orally administered, it is rapidly absorbed with a maximum plasma concentration achieved within 1 h and has a terminal half-life of between 3 to 6 h. The drug is extensively and rapidly metabolized by the liver, primarily by the CYP3A4 enzyme. Although the drug is well tolerated, specific adverse events have been observed, like flushing, headaches, dyspepsia, and visual disturbances. Liver toxicity related to sildenafil consumption has been considered a very rare event. However, in the last decade, some cases of sildenafil-associated hepatotoxicity have been reported. Furthermore, some hepatic intoxications have been reported after the intake of "natural" or "herbal" aphrodisiac supplements sold through Internet, sex shops, social media, and by word-of-mouth found to contain sildenafil and other phosphodiesterase type 5 (PDE-5) inhibitors. Studies investigating a possible link between sildenafil use and liver damage are limited, and the underlying mechanism responsible for hepatotoxicity is still missing. Studies in animals evidence that the hematopoietic function of the liver may have severely been affected as a result of a probable toxic effect of sildenafil. Here, the studies reporting liver toxicity by sildenafil in humans and in animals are reported and discussed.

Hepatotoxicity associated with illicit use of anabolic androgenic steroids in doping.

Anabolic Androgenic Steroids (AAS) abuse and misuse is nowadays a harmful habit involving both professional or recreational athletes, as well as general population. AAS are also frequently present in over-the-counter dietary supplements without being declared in the list of ingredients, leaving consumers unaware of the risks of adverse effects. Indeed, health risks of AAS consumption in pharmaceutical preparations or dietary complements seem still underestimated and under-reported. The variety of complications due to AAS misuse involves cardiovascular, central nervous, musculoskeletal and genitourinary systems of both males and females; psychiatric and behavioral effects, damages to metabolic system, skin and mainly liver. For instance, relevant concern has been raised by the AAS hepatotoxicity including adenoma, hepatocellular carcinoma, cholestasis, and peliosis hepatis. The present review reports the information available on the hepatotoxic effects of AAS use in professional and amateur athletes.

A comparison of a hybrid light-cured glass-ionomer base and liner vs. a light-cured resin tooth fragment attachment.

PURPOSE: The purpose of this study was to compare the dislodgement strengths and fracture types for reattached tooth fragments using a light-cured composite resin material, a hybrid light-cured glass ionomer base, and a hybrid light-cured glass ionomer liner. METHODS: Seventy-five bovine incisor teeth were fractured, randomly divided into three groups of equal number, and then luted back together with three different materials (Universal Bonding Agent/TPH Composite Resin; VariGlass VLC Base; and VariGlass VLC Liner: LD Caulk Div Dentsply Int Inc, Milford, DE). The reattached fragments were subjected to thermocycling with a 40 degrees C differential and then were loaded until the force required to dislodge the fragment was reached. RESULTS: The mean dislodgement strengths were 36.8 (+/- 25.6) kg for the composite resin, 36.4 (+/- 26.7) kg for the glass ionomer base, and 31.4 (+/- 29.5) kg for the glass ionomer liner. Cohesive fractures occurred in 73% of the dislodgements. CONCLUSIONS: There was no statistically significant difference demonstrated (P < 0.05) between the three groups in terms of both dislodgement strength and fracture type.

Solitary plasmacytoma of the vertebral column. A report of 15 cases.

The clinical features and the treatment results of 15 patients with solitary plasmacytoma of the spine observed in a 28-year period (1950-1977) are reported. The signs at presentation were back pain in 4 cases and spinal cord compression in 11 cases. Three of these patients had paraplegia. Radiologically, the alteration encountered was an osteolytic lesion in all cases. The local treatment was radiotherapy in 11 cases and surgery plus radiotherapy in 4 cases. In 3 patients systemic chemotherapy was also employed. Seven patients are alive without signs of disease 3 to 9 years (mean 6 years) after diagnosis. Eight patients developed multiple myeloma in a period ranging from 1 to 8 years (mean 3.5 years). The relationship between multiple myeloma and solitary plasmacytoma of the spine, as well as the best treatment for the latter, are discussed.

The treatment of osteosarcoma of the extremities: twenty year's experience at the Istituto Ortopedico Rizzoli.

Twenty year's (1959-1979) experience in the treatment of osteosarcoma at the Bone Tumor Center of the Istituto Ortopedico Rizzoli is presented. During this period 433 cases were recorded, but only 266 were considered. All the patients underwent surgery but after 1970 whole-lung irradiation (1971), immunotherapy (1971), and chemotherapy (1972 onward) were added as adjuvant therapies on a nonrandomized basis. In the group treated with surgery alone the prognosis was very poor: 10% survived nine years or more after the diagnosis, an average disease-free interval of 7.7 months and an average survival time of 13 months. Monolateral whole-lung irradiation had negative results and was abandoned after six cases. Adjuvant immunotherapy with irradiated autologous tumor cells gave moderately positive results in 16 patients, but only by delaying the appearance of first metastases, therefore increasing the time of survival. Adjuvant chemotherapy was performed with three different protocols: one protocol with ADM only and two protocols using VCR + MTX (at medium dose) + ADM, administered according to two different schedules. Superimposable results were obtained with these three regimens. With equal follow-up, the percentage of continuously disease-free patients treated with adjuvant chemotherapy was significantly higher than that of patients treated with surgery alone (P less than 0.001). The patients in the chemotherapy group who had relapses showed a prolonged time (mean = 12.3 months) to the onset of the first metastasis. Adjuvant chemotherapy caused virtually no morbidity and no deaths. Reference is made to the advantages of a large and homogeneous caseload deriving from a single institution to avoid preselection bias and evaluate the effectiveness of new therapeutic approaches when patient randomization has not been employed.