A rare case of primary thyroid amyloidosis.

INTRODUCTION: Amyloid goiter is due to the deposition of amyloid in the thyroid, resulting with enlargement of the gland and compressive symptoms. CASE: We herein present a case of a 45-year-old male patient who complained of a big swelling in the neck. Ultrasound showed an enlarged thyroid gland with mediastinal involvement. The multinodular appearance was consistent with the diagnosis of multinodular goiter. He had a history of multiple myeloma but no sign of systemic amyloidosis. DISCUSSION: Thyroid gland was removed and the histopathological examination revealed a diffuse deposition of amyloid associated with metaplastic lipomatosis of the stroma. CONCLUSIONS: The treatment of choice in patients with amyloid goiter is total thyroidectomy to solve compression symptoms.

Anti-HIV activity of new higher order G-quadruplex aptamers obtained from tetra-end-linked oligonucleotides.

By combining the ability of short G-rich oligodeoxyribonucleotides (ODNs) containing the sequence 5'CGGA3' to form higher order G-quadruplex (G4) complexes with the tetra-end-linked (TEL) concept to produce aptamers targeting the HIV envelope glycoprotein 120 (gp120), three new TEL-ODNs (1-3) having the sequence 5'CGGAGG3' were synthesized with the aim of studying the effect of G4 dimerization on their anti-HIV activity. Furthermore, in order to investigate the effect of the groups at the 5' position, the 5' ends of 1-3 were left uncapped (1) or capped with either the lipophilic dimethoxytrityl (DMT) (2) or the hydrophilic glucosyl-4-phosphate (3) moieties. The here reported results demonstrate that only the DMT-substituted TEL-ODN 2 is effective in protecting human MT-4 cell cultures from HIV infection (76% max protection), notwithstanding all the three new aptamers proved to be capable of forming stable higher order dimeric G4s when annealed in K+-containing buffer, thus suggesting that the recognition of a hydrophobic pocket on the target glycoprotein by the aptamers represents a main structural feature for triggering their anti-HIV activity.

Role of bisphenol A as environmental factor in the promotion of non-alcoholic fatty liver disease: in vitro and clinical study.

BACKGROUND: Bisphenol A is an endocrine disrupting chemical associated with type 2 diabetes mellitus (T2DM), cardiovascular disease and liver enzyme abnormalities. AIM: To evaluate bisphenol A plasma and urine levels in non-alcoholic fatty liver disease (NAFLD) patients compared to healthy subjects. Furthermore, we evaluated, in human HepG2 cells, the effects of exposure to different concentrations of bisphenol A on both oxidative stress induction and cell proliferation. METHODS: We enrolled 60 patients with histological diagnosis of NAFLD with or without T2DM and sixty healthy subjects. In vitro, the proliferation of bisphenol A-exposed HepG2 cells at two different concentrations (0.025 and 0.05 µM) was evaluated, both at high (H-HepG2) and at low (L-HepG2) glucose concentrations for 48 h. Lipoperoxidation was assessed by thiobarbituric acid reactive substances (TBARS) assay. RESULTS: Bisphenol A levels were significantly higher in 60 NAFLD subjects, both in urine and in plasma (P < 0.0001) when compared to controls and, in this group, it appeared to be higher in 30 non-alcoholic steatohepatitis patients compared to 30 simple steatosis subjects (P < 0.05), independently from the presence of T2DM. After a bisphenol A-free diet for 1 month, NAFLD patients showed a significant reduction in bisphenol A circulating levels (P < 0.05), without a significant reduction in urine levels. H-HepG2 cells treated with bisphenol A (0.05 µM) increased proliferation compared to controls at 48 h (P < 0.0001). Bisphenol A increased TBARS levels at 48 h versus controls. CONCLUSIONS: Our study reveals a possible role of bisphenol A as an environmental factor involved in the promotion of NAFLD, particularly in T2DM patients.

Nasal photodisinfection and chlorhexidine wipes decrease surgical site infections: a historical control study and propensity analysis.

BACKGROUND: Pre-operative decolonization therapy (DcTx) using chlorhexidine (CHG) body washes and/or intranasal mupirocin can reduce surgical site infections (SSIs), but compliance is often suboptimal. AIM: To assess the effectiveness of immediate DcTx using a novel approach of intranasal antimicrobial photodisinfection therapy (PDT) combined with CHG body wipes for the reduction of SSIs. METHODS: Between 1(st) September 2011 and 31(st) August 2012, 3068 elective cardiac, orthopaedic, spinal, vascular, thoracic and neurosurgical patients were treated with CHG in the 24h preceding surgery, and received intranasal PDT in the pre-operative area. SSI surveillance methodology remained unchanged from previous years and patients were followed for one year. Results were compared with those for a four-year historical control group of 12,387 patients as well as those for a concurrent control group of 206 untreated patients. FINDINGS: A significant reduction in the SSI rate was observed between treated patients and the historical control group [1.6% vs 2.7%, P = 0.0004, odds ratio (OR) 1.73, 95% confidence interval (CI) 1.2815-2.3453]. This significant reduction was maintained on intent-to-treat analysis (P = 0.021, OR 1.37, 95% CI 1.0476−1.7854) [corrected]. Overall compliance with DcTx was 94%. A 1:4 propensity score analysis of matched treated and untreated patients demonstrated that DcTx reduced the risk of SSIs significantly (P = 0.00026, z = 3.65). CONCLUSION: The combination of CHG wipes and PDT immediately before surgery reduced SSIs, achieved excellent compliance, and was easily integrated into the pre-operative routine.

Data available on the extent of cocaine use and dependence: biochemistry, pharmacologic effects and global burden of disease of cocaine abusers.

Drug use is seen more as an individualistic behaviour and is therefore not readily conceived of from a population perspective. There is general recognition of several phases and degrees of drug abuse, from initiation and early-use patterns to long-term chronic use. Cocaine and its derivative "crack" cocaine provide an example of both the globalization of substance use and the cyclical nature of drug epidemics. Cocaine is a powerful CNS (Central Nervous System) stimulant but exerts its action in a several types of adverse health effects, including acute toxic effects (i.e. overdose, accidental injury and violence), dependence, cardiovascular disease, cirrhosis, bloodborne bacterial and viral infections, and mental disorders. Of interest, many people who use Cocaine will use also other drugs; therefore, ascribing adverse health effect to a certain drug might be difficult. Any mucous membrane can act as a port of entry for cocaine and the systemic effect is greatly influenced by the route and speed of administration. The effects of Cocaine mainly depend on the user's addiction, the dose received and the mode of assumption. Laws restricting the availability of cocaine saw a decrease in consumption in these countries until the 1960s. The number of cocaine users worldwide ranged from 14 million to 21 million (0.3-0.5% of the population aged 15-64 years). The largest market was North America, then western and central Europe and South America.

Lethal injuries following building collapse: comparison between autopsy and radiographic findings.

PURPOSE: The aim of this study was to evaluate the impact of conventional radiology on the assessment of causes of death of human beings after a building collapse and to establish whether the radiographic approach is useful and justifiable. MATERIALS AND METHODS: Eight victims of a building collapse were subjected to autopsy, toxicology and radiographic examinations of the entire body. The autopsy findings, classified into three groups according to the New Injury Severity Score (NISS), were compared with radiographic findings. RESULTS: The death of the three individuals in group 1 was ascribed to mechanical asphyxia. Costal fractures, pneumothorax and subcutaneous emphysema were detected in one case only. The three individuals in group 2 died of mechanical asphyxia associated with cerebral injuries in all cases, abdominal injuries in two and cardiac injuries in one. Plain films showed skull fracture in one case, air within the cardiac chambers in another and diaphragmatic injuries in the third. The two individuals in group 3 died of injuries not compatible with life at the cardiac and abdominal level in both cases and at the cerebral level in one. Radiography showed multiple fractures of the cranium associated with diaphragmatic injuries in one case only. No significant pleuropulmonary radiographic findings were detected in any of the eight victims. Paralytic ileus, identified in all patients, is not strictly correlated to abdominal injuries. Skeletal injuries were all confirmed at conventional radiography. CONCLUSIONS: Conventional radiography allows for the overall assessment of skeletal injuries. Radiographic findings provide limited information about the causes of death, whereas findings related to the concomitant causes of death are more frequent. Conventional radiography should be considered inadequate, especially if the potential of the modern software tools available on current computed tomography and magnetic resonance images is considered.

Immunohistochemical characterisation and TNF-α expression of the granulomatous infiltration of the brainstem in a case of sudden death due to neurosarcoidosis.

Neurosarcoidosis carries a mortality of 10%, over twice that of sarcoidosis overall, although it has been rarely reported as a cause of sudden death. The current evidence suggests that sarcoidosis results from an enhanced immune reaction to a variety of antigens, non-self or self which causes CD4 (helper-inducer) T-cell accumulation with a ratio of helper-inducer T cells to suppressor-cytotoxic T cells usually high in affected organs, activation and release of inflammatory cytokines, and formation of granulomatous lesions. Numerous cytokines and other mediators are produced by both activated macrophages and T lymphocytes bearing the CD4-helper phenotype during the granuloma responses. A number of data suggest that interferon-gamma (IFN-gamma) and cytokines such as TNF-α, IL-2, and IL-18 play a critical role in the formation of granulomas. In this article, we describe the clinical and pathological characteristics of a patient who suddenly died due to acute respiratory failure. Neurosarcoidosis with massive and extensive involvement of the brainstem was established as the cause of death. Western blot analysis in the patient demonstrated the TNF-α presence as a 51-kDa protein in the brain tissue. The immunohistochemical analysis showed a poor positiveness for CD4 in all samples around the granulomas, as well as moderate positiveness for CD8, CD15, and CD20; CD45 and CD68 showed a strong positiveness in all the brain samples. Histological findings, immunohistochemical analysis, and proteomic studies addressed the diagnosis of neurosarcoidosis with involvement of the nucleus of the solitary tract in the brainstem and central hypoventilation as the cause of death.

Cold affects the transcription of fatty acid desaturases and oil quality in the fruit of Olea europaea L. genotypes with different cold hardiness.

The olive tree lacks dormancy and is low temperature sensitive, with differences in cold tolerance and oil quality among genotypes. The oil is produced in the drupe, and the unsaturated fatty acids contribute to its quality. The aim of the present research was to investigate the relationship among development, cold response, expression of fatty acid desaturase (FAD) genes, and unsaturated fatty acid composition in drupes belonging to genotypes differing in leaf cold tolerance, but producing good oil (i.e. the non-hardy Moraiolo, the semi-hardy Frantoio, and the hardy Canino). In all genotypes, cold sensitivity, evaluated by cold-induced transient increases in cytosolic calcium, was high in the epi-mesocarp cells before oil body formation, and decreased during oil biogenesis. However, genotype-dependent differences in cold sensitivity appeared at the end of oil production. Genotype-dependent differences in FAD2.1, FAD2.2, FAD6, and FAD7 expression levels occurred in the epi-mesocarp cells during the oleogenic period. However, FAD2.1 and FAD7 were always the highest in the first part of this period. FAD2.2 and FAD7 increased after cold applications during oleogenesis, independently of the genotype. Unsaturated fatty acids increased in the drupes of the non-hardy genotype, but not in those of the hardy one, after cold exposure at the time of the highest FAD transcription. The results show a direct relationship between FAD expression and lipid desaturation in the drupes of the cold-sensitive genotype, and an inverse relationship in those of the cold-resistant genotype, suggesting that drupe cold acclimation requires a fine FAD post-transcriptional regulation. Hypotheses relating FAD desaturation to storage and membrane lipids, and genotype cold hardiness are discussed.

Renal heat shock proteins over-expression due to anabolic androgenic steroids abuse.

Chronic use of anabolic adrogenic steroids (AAS) has been known to cause serious adverse effects. While the effects of AASs on cardiovascular system are well known, toxicity on other organs has received less attention. A doserelated nephrotoxic effect has been proposed and a wide variety of morpho-functional damages have been observed, but the exact pathophysiological mechanism of action is still not well known. In the present minireview, we highlight the remaining issues through an analysis of the pertinent literature. As with HSPs toxic agents their overexpression could be considered a protective reaction against AAS abuse however, comprehensive studies concerning the whole range of Hsps/chaperones expressions in all organs after long term use of AAS are needed.

MDMA administration and heat shock proteins response: foreseeing a molecular link.

Molecular and cellular mechanisms of MDMA-induced toxicity have been extensively studied in a number of experimental models. Nevertheless, only few studies investigated the involvement of HSPs ("molecular chaperones") in MDMA organs toxicity. In the present minireview we highlight this subject analysing the results of these studies conducted especially on brain tissue. Despite of it seems obvious that HSPs overexpression is a protective reaction against MDMA treatment, the molecular mechanisms for exerting their action are far to be undiscovered. At the same time, we need of comprehensive studies concerning the whole range of Hsps/chaperones expressions in all organs after acute and chronic administration of MDMA.

Megalencephaly and perisylvian polymicrogyria with postaxial polydactyly and hydrocephalus (MPPH): report of a new case.

Megalencephaly (MEG), or enlargement of the brain, can either represent a familial variant with normal cerebral structure, or a rare brain malformation associated with developmental delay and neurological problems. MEG has been split into two subtypes: anatomical and metabolic. The latter features a build-up inside the cells owing to metabolic causes. Anatomical MEG has been detected in many different conditions, including many overgrowth syndromes. In 2004 Mirzaa et al. reported five non-consanguineous patients with a new MCA/MR syndrome characterized by severe congenital MEG with polymicrogyria (PMG), postaxial polydactyly (POLY) and hydrocephalus (HYD). The authors argued that these findings identified a new and distinct malformation syndrome, which they named MPPH. We report on a new case of MPPH, the first to be described after the original series (Mirzaa et al., 2004).

An unusual case of crossbow homicide.

The authors report the case of a man found unresponsive in a wooded area with injuries on the face, eyes, shoulders and back, probably produced by caustic agents. A penetrating wound was noted in the left occipital region. Four days after admission to an Intensive Care Unit he died. No weapon was found at the crime scene. Autopsy revealed an occipital bone defect in the wound area, and cerebral haemorrhage in the left hemisphere in the absence of an exit wound. Immunohistochemical staining of brain samples for ß-APP were critical establishing the extent of the injury. The peculiarity of the wound and the lack of circumstantial evidence made it necessary to conduct a careful investigation to identify the weapon. Firing tests performed on experimental cranial models established the use of a crossbow weapon as a cause of the observed wound.

HLA allele frequency and clinical outcome in Italian patients with cutaneous melanoma.

The current study focuses the analysis on the possible relationship between HLA allele frequency and clinical outcome of melanoma in a population of 382 Italian patients, as compared with 203 ethnically matched controls. In a 3-year follow-up study, results showed significant differences between groups of patients selected according to clinical stage, histology, and progression of the disease. A*01 seems to be correlated with a less aggressive variant of the disease, whereas DRB1*01-DQB1*0501 seems to be associated with metastatic progression of melanoma. Moreover, a negative association with B*13, B*44, as well as with DRB1*04-DQB1*0302 was found. A multivariate logistic regression model showed HLA-DRB1*04 to behave as an independent favorable prognostic marker of melanoma in our population (OR = 2.34, CI = 1.15-4.74).

Inhibition and regulation of rat liver L-threonine dehydrogenase by different fatty acids and their derivatives.

Rat liver L-threonine dehydrogenase is a mitochondrial enzyme which transforms L-threonine either into aminoacetone or into acetyl-CoA. We show that it is inhibited by several fatty acids and their derivatives: short chain fatty acids, L-2-hydroxybutyrate and D-3-hydroxybutyrate, long chain fatty acids, such as lauric acid, myristic acid, palmitic and stearic acids, bicarboxylic acids such as malonic acid and its derivatives methyl- and hydroxymalonic acids. The inhibition occurs at low and physiological concentrations of such compounds, which are normally present and metabolized in mitochondria. It presumably plays a role in the physiology of acetyl-CoA-dependent formation of fatty acids and ketobodies, in L-threonine-dependent gluconeogenesis, and in the regulation of L-threonine metabolism by L-threonine dehydrogenase and L-threonine deaminase.

Crohn disease: susceptibility and disease heterogeneity revealed by HLA genotyping.

Predisposition to Crohn disease (CD) seems to be genetically determined but, though several reports on the matter, the association between HLA antigens and the disease is still controversial. PCR-SSP high resolution typing in 107 CD patients, and in subgroups selected according to clinical features, showed a positive association with the rare haplotype DRB1*07, DQB1*0303 both in the overall patients (p = 0.002; pc = ns) and in the subgroup of nonfistulized patients (p = 0.0008; pc = 0.032). Moreover, the protective role of the haplotype DRB1*03, DQB1*0201 (p = 0.029) was confirmed also in Italian patients, whereas no strong association with HLA class I alleles has been found. In addition, variability of the HLA alleles frequency in CD subgroups was observed, supporting the hypothesis of a genetic heterogeneity of the disease and suggesting that HLA alleles distribution in selected groups may allow to identify patients with probably different prognosis or associated complications.

CD40 expressed on human melanoma cells mediates T cell co-stimulation and tumor cell growth.

CD40 is a 50 kDa molecule, a member of the tumor necrosis factor/nerve growth factor receptor family. It is expressed on B cells, monocytes, dendritic cells and various malignant cells. While the critical relevance of this molecule in T cell-dependent B cell activation is already established, the biological role of CD40-CD154 interaction in non-hematopoietic cells is still unknown. Here we show that CD40 is functionally expressed on human melanoma-derived cell lines. No correlation between surface CD40 expression and the origin of the cell line, primary versus metastatic, was observed. Melanoma cells were shown to be able to co-stimulate TCR-triggered human T cells; moreover, because they do not express CD80 or CD86 co-stimulatory structures, the involvement of additional pathways have to be postulated. We have identified CD40 as one of the molecules involved in melanoma cell-mediated co-stimulation of anti-CD3-triggered human CD4(+) T lymphocytes. In addition, a CD40-dependent pathway, able to enhance tumor cell proliferation at low serum concentrations, in vitro, has been shown to be functional in human melanoma cell lines.

Hypertension in the elderly is associated with impaired glucose metabolism independently of obesity and glucose intolerance.

We evaluated insulin secretion, insulin sensitivity and blood pressure changes after oral administration of glucose in hypertensive and normotensive elderly subjects. The hypertensive group consisted of 12 subjects (aged 72.5 +/- 1.9 years, mean +/- s.e.m.) who had a history of hypertension lasting 10-25 years and were not more than 20% above ideal body weight. The normotensive group consisted of 12 subjects matched to the hypertensive group for age, sex and weight. All subjects underwent an oral glucose tolerance test (75 g glucose dissolved in 300 ml water), an intravenous glucose tolerance test (0.33 g/kg of a 50% glucose solution) and a euglycaemic, moderately hyperinsulinaemic glucose clamp. In both groups, oral glucose tolerance was normal according to the criteria of the National Diabetes Data Group; the hypertensive group showed significantly higher plasma glucose and insulin responses to oral glucose than the normotensive group, suggesting insulin resistance. The results of the euglycaemic clamp confirmed the state of reduced insulin sensitivity. Our data demonstrate that oral but not intravenous glucose produces a fall in blood pressure in hypertensive but not in normotensive patients, probably because activation of the sympathetic nervous system is impaired in hypertensive subjects; moreover, hypertension in the elderly seems associated with a state of reduced sensitivity to insulin.

Effects of the angiotensin converting enzyme inhibitor enalapril compared with diuretic therapy in elderly hypertensive patients.

The aim of this study was to evaluate the usefulness of the angiotensin converting enzyme (ACE) inhibitor enalapril in a group of 30 patients (mean age 73.3 years) with moderate hypertension and normal haematological and chemical parameters (170 +/- 8.1 mmHg systolic and 104 +/- 5.8 mmHg diastolic blood pressure), who were receiving diuretic therapy with chlorthalidone (12.5 mg/day). This therapy caused a significant decrease in systolic and diastolic blood pressure (to 165 +/- 6.7 and 98 +/- 4.7 mmHg, respectively; P less than 0.001) but it also induced hypokalaemia (3.04 +/- 0.7 mmol/l; P less than 0.001) and multiple (greater than 10/h) and complex premature ventricular depolarizations (2nd, 3rd and 4th Lown grade). Enalapril treatment (5 mg/day for 5 days and 10 mg thereafter) was added to the diuretic therapy and after 2 months a further decrease in blood pressure was observed (to 158 +/- 5.6 mmHg systolic, P less than 0.001; 87.2 +/- 5.0 mmHg diastolic, P less than 0.001). Moreover, there was a significant reduction in the mean heart rate (from 79 to 72 beats/min, P less than 0.005) and an increase in serum potassium (to 4.19 +/- 0.2 mmol/l; P less than 0.001). In 80% of patients a 24-h dynamic electrocardiogram showed a significant reduction in both the number and complexity of premature ventricular depolarizations. Our findings suggest that ACE inhibitors can be useful in patients developing hypokalaemia during therapy. However, we are not yet able to explain the beneficial effects of enalapril in decreasing the frequency of premature ventricular depolarizations.