Correction of vitamin D status by calcidiol: pharmacokinetic profile, safety, and biochemical effects on bone and mineral metabolism of daily and weekly dosage regimens.

RATIONALE: Calcidiol can be employed to correct vitamin D deficiency. MAIN RESULTS: Calcidiol administered at daily and weekly regimens over a period of 3 months was able to successfully raise 25-hydroxyvitamin D levels without altering other markers related to bone and mineral metabolism. SIGNIFICANCE: Calcidiol supplementation is effective and safe. INTRODUCTION: The correction of vitamin D status is necessary to maintain an optimal mineral and skeletal homeostasis. Despite cholecalciferol (vitamin D3) is the most commonly used drug for vitamin D supplementation, the more hydrophilic compound calcidiol (25-hydroxyvitamin D3) can be employed at daily, weekly, and monthly regimens to reach in the short term the target levels of serum 25-hydroxyvitamin D [25(OH)D]. In the administration of different doses of calcidiol pharmacokinetic study (ADDI-D study), the efficacy and safety of daily and weekly dosages of calcidiol were tested. METHODS: A total of 87 Caucasian, community-dwelling, postmenopausal women, aged 55 years or older, with vitamin D inadequacy (serum 25(OH)D levels <30 ng/ml, with mean 25(OH)D below 20 ng/ml, namely 16.5 ± 7.5 ng/ml) were randomized to receive three different dosages of calcidiol: 20 µg/day, 40 µg/day, and 125 µg/week for 3 months. The attained level of serum 25(OH)D was selected as primary endpoint to assess efficacy, while other parameters of mineral metabolism, (serum calcium, parathyroid hormone, phosphate, FGF23, urinary calcium, and markers of bone turnover) were assessed as secondary endpoints to establish safety. RESULTS: In all the three groups, serum 25(OH)D values significantly and promptly rose and plateaued above the 30 ng/ml threshold remaining within safety interval after 14 days of treatment, with similar efficacy for the similar daily and weekly dose regimens. The different dosages were also equally effective in controlling secondary hyperparathyroidism. No significant changes in calcium and phosphate metabolism and in bone turnover markers were observed for any of the treatments, confirming the safety of this compound. CONCLUSIONS: The results of this study demonstrate the short- and mid-term efficacy and safety on core parameters of mineral metabolism of different daily or weekly dosages of calcidiol when used to treat vitamin D inadequacy or deficiency in postmenopausal women. Further studies are needed to assess falls as primary outcome of calcidiol supplementation.

Effect of risedronate in osteoporotic HIV males, according to gonadal status: a pilot study.

The aim of the study was to evaluate the effect of risedronate on bone mineral density (BMD) and bone turnover markers in HIV-infected osteoporotic males, according to their gonadal status. HIV patients were followed up for 24 months and divided into two groups: patients with osteoporosis or osteopenia with fractures (group A, n = 20) and those without (group B, n = 21). Group A and B were further divided according to the presence of reduced androgenizations. Both groups were treated with cholecalciferol 800 I.U. and calcium (Ca) 1,000 mg orally every day for the first 12 months. Risedronate 75 mg for two consecutive days a month orally was then added in group A, for another 12 months. Group B continued treatment with Ca and vitamin D. Every 6 months each patient underwent biochemical evaluation, and BMD measurement. A significant increase in lumbar BMD was observed in HIV males with adequate androgenization after 12 months of risedronate treatment in group A together with a reduction of bone turnover markers. BMD remained stable with a concomitant significant slight reduction of bone turnover markers in group B. Risedronate increased BMD and reduced bone turnover markers to a greater extent in patients with adequate androgenization compared to osteoporotic HIV males with symptomatic hypoandrogenization.

Warthin's tumor distribution within the parotid gland. A feasible etiologic source from lymph nodal tissue.

AIM: Warthin's tumor (WT) is the second commonest parotid gland neoplasm after pleomorphic adenoma (PA). It mainly arises from the lower pole of the superficial parotid lobe (i.e., tail of gland), a site with the greatest distribution of intra-parotid lymph nodes, and its definitive etiopathogenesis is still unclear. The aim of this study was to support the strict topic and etiologic link hypothesised between this tumor and the intraparotid lymph nodes, as being massively present in the tail, by assessing the WT distribution within the parotid gland. METHODS: Seventy-one WTs excised from 64 patients were compared retrospectively with 134 PAs from 133 patients, as controls. In all sample, staging of parotid gland tumors was defined by sonography and magnetic resonance imaging. Furthermore, tumor localization, size, bilaterality and multifocality were assessed according to radiological, intraoperative and histopathological findings. RESULTS: WTs were mainly detected in the tail (73%), less in the superficial lobe (23%) and the deep one (4%). WT presented with bilateral and synchronous lesions in 10% of cases vs. 0.75% of controls. CONCLUSION: Since the tail has been well known to present the greatest distribution of intra-parotid lymph nodes, our clinical findings on WT parotid localization could suggest the possible origin of this tumor from epithelial salivary gland ductal inclusions, as being likely entrapped during embryogenesis within the intra-parotid lymph nodes, and could support the hypothesis of a heterotopy in the pathogenesis of WT. However, this suggestive hypothesis based only on clinical and "topographic" data should be confirmed by histopathological studies about the presence of the salivary ductal elements trapped within the intra-parotid lymph nodes.

Squamous cell carcinoma arising from long-term (50-year) Lupus vulgaris: is there a need for a close medical follow-up in such chronic diseases?

Skin manifestations of tuberculous infection (Mycobacterium tuberculosis) are represented by miliary tuberculosis of the skin, tuberculous chancre, scrofuloderma, tuberculosis verrucosa cutis, periorificial tuberculosis, and lupus vulgaris (LV). Among this group, LV is the most common skin condition, diagnosed in 10% of tuberculotic patients. The authors report herein a case of squamous cell carcinoma (SCC) arising from long-standing (50-year) LV and underline the need of an extensive follow-up of tuberculotic lesions.

Surgical treatment with Ligasure Precise of schwannoma of brachial plexus: case report.

English version We present a case of bulky schwannoma arising from the brachial plexus treated by a new surgical device. A 38-year-old man presented with a slow-growing left-sided supraclavicular mass and complained paresthesia of the third and forth fingers of the hand and forearm weakness. Physical examination revealed Tinel's sign. A CT-scan revealed a solid mass situated in the left profound supraclavicular fossa. The tumour was resected with the utilization of bipolar vessel sealing system (Ligasure Precise). This device is very useful in sutureless removal of masses localized in deep supraclavicular fossa. During the operation, care was taken to preserve the nerve function.

Neoformation of boldenone and related steroids in faeces of veal calves.

Conflicting findings regarding the boldenone content of bovine faeces suggest it may be synthesized de novo in emitted faeces. We tested this hypothesis by analysing uncontaminated urine, fresh and various forms of dried faeces from 10 calves (not given boldenone) by liquid chromatography/tandem mass spectrometry for 17alpha- and 17beta-boldenone (alpha and beta BOL); 1,4-androstadiene-3,17-dione (ADD); 4-androstene-3,17-dione (AED), testosterone (T) and epitestosterone (ET). Urine contained no alpha BOL, beta BOL or ADD. The analysed substances were variably present in the rectal faeces, and at generally higher levels in faeces scraped from skin or stall floor. In pooled rectal faeces naturally dried for 13 days, alpha BOL, ADD, AED and ET levels were extremely high (much higher than accounted for by increases due to drying), and beta BOL and T were absent. It is concluded that de novo synthesis of alpha BOL and metabolites occurs naturally in bovine faeces and only uncontaminated urine should be analysed for illegal boldenone.

Computer-assisted evaluation of isoelectric focusing patterns in electrophoretic gels: identification of smoothhounds (Mustelus mustelus, Mustelus asterias) and comparison with lower value shark species.

In this work, the most commercially important Selachian species, smoothhound (Mustelus mustelus) and starry smoothhound (Mustelus asterias), have been identified by polyacrylamide isoelectric focusing (IEF-PAGE), along with several shark species of minor commercial value. In Italy, these two smoothhound species are commonly subjected to fraudulent substitution with lesser valued sharks. After the electrophoretic runs, the band patterns of the two Mustelus species were compared with those of dogfish (Scyliorhinus canicula), spurdog (Squalus acanthias), blue shark (Prionace glauca) and black-mouthed dogfish (Galeus melanostomus), both visually and with gel analysis software. The actual isoelectric points were then submitted to cluster analysis to differentiate the single species, despite the possible occurrence of electrophoretic variations or protein polymorphism. Every shark showed species-specific band patterns and could therefore be well differentiated, as confirmed by statistical analysis.

[Efficacy and safety of ambulatory electric cardioversion of atrial fibrillation with monophasic and biphasic shock]. / Efficacia e sicurezza della cardioversione elettrica della fibrillazione atriale in regime di day-hospital con shock mono e bifasico.

BACKGROUND: The aim of this study was to evaluate the safety and efficacy of ambulatory external cardioversion (EC) by means of monophasic and biphasic shock in patients with persistent atrial fibrillation (AF). METHODS: One hundred and twenty-seven consecutive patients with AF were submitted to EC, preceded by short general anesthesia with propofol, after pretreatment with oral anticoagulants for at least 3 weeks and, if not contraindicated, with amiodarone. In 87 of these patients we used monophasic shock and in 40 patients we used biphasic shock. Our protocol provided for up to 3 shocks delivered at an energy level ranging between 200 and 360 J for monophasic and from 70 to 175 J for biphasic shock. The patients were discharged after 4 hours of ECG monitoring and following a determination of serum CK-MB at the fourth hour. RESULTS: The mean age of the patients submitted to EC with monophasic and biphasic shock (65 +/- 9 vs 67 +/- 7 years) and the duration of AF (34 +/- 22 vs 32 +/- 25 days) were similar. The efficacy of EC with monophasic shock was 85% and the mean energy delivered was 266 +/- 81.5 J. The efficacy of the EC with biphasic shock was 98% and the mean energy delivered was 127 +/- 40 J. The difference between the percentage of efficacy and the number of joules delivered was statistically significant (p < 0.05). The mean value of the CK-MB after 4 hours following delivery of the shock was not significantly different: 2.5 ng/ml for monophasic vs 1.7 ng/ml for biphasic shock (p = NS). CONCLUSIONS: In our patients, ambulatory EC of persistent AF is safe and feasible; biphasic shock is more efficacious and requires less energy with respect to monophasic shock.

Substitution of fish species detected by thin-layer isoelectric focusing and a computer-assisted method for the evaluation of gels.

Fourteen fish species susceptible to substitution were analysed by the thin-layer isoelectric focusing technique on polyacrylamide gels of pH 3.5-9.5. Four fish per species were run on the same gel to verify the possibility to differentiate them according to their protein banding patterns. The occurrence of intraspecific differences due either to electrophoretic variations or to protein polymorphism was also observed. In fact, some of them showed few dissimilarities among their protein profiles. However, the differentiation was possible for all species, even for those belonging to the same order, family and genus. Computer-based tools combined with statistical analysis were implemented and usefully applied to avoid a subjective evaluation of the isoelectric focusing gels, and to verify the reliability of the preliminary visual comparison of protein patterns.

Gas chromatographic determination of galactose in milk. Example of a switching valve used for the protection of the capillary column.

Galactose, a marker of heat treatment, has been analysed in milk as pentafluorobenzyloxime acetate by gas chromatography with flame ionization detection using a simple switching valve system. The procedure did not entail any prederivatization clean-up for lactose elimination from the sample. In a short pre-column, reagent and lactose derivative excess were separated and the galactose and internal standard derivatives were transferred to the analytical column by a four-port valve. Thus, the analytical column was protected from overloading, so avoiding rapid deterioration.

A new procedure for the specific high-performance liquid chromatographic determination of hydroxyproline.

A procedure suitable for a selective high-performance liquid chromatographic (HPLC) analysis of the imino acid hydroxyproline in the presence of a large excess of amino acids is proposed. To deaminate the amino acids, the well-known reaction with nitrous acid is exploited. The N-nitroso derivatives of imino acids obtained are extracted in ethyl acetate, denitrosated by hydrobromic acid, and treated with dabsyl-chloride. The final HPLC separations are carried out on a reversed-phase column in a rapid isocratic run. The use of the cis isomer of hydroxyproline as an internal standard allows good reproducibility. As an application of the described method, the hydroxyproline content in samples containing collagen and an excess of bovine serum albumine (up to 20:1) is determined.

Age-related differences of blood pressure profile in essential hypertension.

The purpose was to assess age-related circadian changes of blood pressure profile (BPP) employing a truncated Fourier series with four harmonics (tFs) in patients with essential hypertension. The study was performed on 32 patients with essential hypertension divided in two groups: (A) 15 patients younger than 55 years and (B) 17 patients older than 60 years. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were monitored every 20 minutes for 24 h with a noninvasive portable device (SpaceLabs 90202). To evaluate the existence of SBP and DBP circadian rhythms a one-sample runs-test was performed and the mesor, amplitude, and acrophase from the overall curve of each patient were obtained by tFs. In both groups, SBP and DBP profiles showed a first peak in the late morning and a second peak in the early evening around the same hours. The two peaks in the SBP profile were higher and the two peaks in the DBP profile were lower in older patients than in younger ones (p < .01, p < .05, p < .3, p < .05). The truncated Fourier series with four harmonics evidences different age-related BP profiles characterized by two peaks with higher SBP and lower DBP in elderly patients. These changes of BPP are in accordance with the reported higher risk of cardiovascular events observed around the same hours.

Neutrophil-derived superoxide anion induces lipid peroxidation and stimulates collagen synthesis in human hepatic stellate cells: role of nitric oxide.

Experimental evidence indicates that the lipid peroxidation of biological membranes is often associated with the development of liver fibrosis. We have studied the effect of neutrophil-derived reactive oxygen species (ROS) on collagen synthesis by human hepatic stellate cells (HSC), the major source of collagen in the liver, in a coculture system. Lipid peroxidation in the cocultures was evaluated in terms of either malondialdehyde (MDA) production or the formation of MDA/4-hydroxynonenal protein adducts. The expression of cellular messenger RNAs (mRNAs) was evaluated by either Northern blotting or RNAse protection assay. Nitric oxide (NO) synthase activity in cells was measured by [3H]citrulline formation from [3H]arginine. In vitro exposure of HSC to ROS resulted in the early induction of lipid peroxidation and was associated with a marked increase (threefold) of procollagen I mRNA expression and synthesis. The addition of antioxidants, such as vitamin E or superoxide dismutase (SOD), impaired this stimulation. The inhibition of neutrophil NO formation by N(G)-monomethyl-L-arginine made the ROS-induced stimulation of procollagen I more evident. The addition of xanthine/xanthine oxidase X/XO, a superoxide anion donor, to HSC cultures strongly increased procollagen I synthesis. This stimulation was hampered by the addition of both SOD and sodium nitroprusside (an NO donor). The contribution of HSC to the production of NO in our coculture system was negligible, because inducible NO synthase (iNOS) mRNA was almost undetectable in these cells, and also because the amount of NO produced by HSC stimulated with tumor necrosis factor alpha (TNF-alpha) and lipopolysaccharide (LPS) was 500 times less than that synthesized by neutrophils. In conclusion, these results indicate that neutrophil-derived ROS may contribute to the development of hepatic fibrosis associated with alcoholic hepatitis. NO produced by neutrophils may exert a "protective" antioxidant effect by operating as a scavenger of superoxide anion.

Efeitos da lasalocida sobre a produçäo de vacas leiteiras em sistema semi-intensivo / Lasalocid effects on dairy cows production of in a semi-intensive management system

Foram estudados os efeitos da lasalocida sobre a produçäo de leite, teor e percentagem de gordura no leite, variaçöes de peso e condiçöes corporais de 18 vacas leiteiras do ecótipo Mantiqueira, com média de 75 dias pós-parto ao início do experimento, alimentadas com 1,0 kg de mistura de concentrados para cada 2,5 kg de leite produzidos acima dos primeiros 4,0 kg, capim elefante (Pennisetum purpureum, var. Napier) picado, fornecido no cocho, e pastagem de Bracharia brizantha. Utilizou-se um delineamento em blocos casualizados e os tratamentos consistiram na administraçäo diária de 0,200 e 300 mg de lasalocida/animal. O experimento teve duraçäo de 17 semanas, sendo as quatro primeiras destinadas ao período de adaptaçäo. Independente da dose empregada a lasalocida näo alterou significativamente a produçäo de leite e a produçäo de leite corrigida a 4 por cento de gordura, porém o grupo tratado com 200 mg apresentou maior porcentagem de gordura no leite (P<0,05). Os grupos tratados com 200 e 300 mg apresentaram ganhos de peso, porém näo estatisticamente menores em relaçäo aos animais controle, quando os dados foram analisados como percentagem de peso vivo. Näo foi observada alteraçäo na condiçäo corporal dos animais

Induction of procollagen type I gene expression and synthesis in human hepatic stellate cells by 4-hydroxy-2,3-nonenal and other 4-hydroxy-2,3-alkenals is related to their molecular structure.

4-Hydroxy-2,3-nonenal (HNE) has been shown to induce procollagen type I gene expression and synthesis in hepatic stellate cells (HSC), i.e. the cells responsible for deposition of collagen and other extracellular matrix proteins in fibrotic liver. Here we report that the stimulatory effect of HNE mostly depends on the contemporary presence of the hydroxyl group in position C4 and of the double bond between position C2 and C3 since equimolar concentrations of 2,3-nonenal as well as of nonenal did not procollagen type I synthesis either at mRNA or at protein levels. Accordingly to this concept, all the other 4-hydroxy-2,3-alkenals of different chain length tested on cultured human HSC (4-hydroxy-2,3-hexenal, 4-hydroxy-2,3-octenal and 4-hydroxy-2,3-undecenal) strongly induced procollagen type I gene expression and synthesis. The stimulatory effect of 4-hydroxy-2,3-alkenals may depend on the well known ability of these aldehydes to react with either SH-groups or NH2-groups of functional proteins.

[Controlled trabeculectomy and incidence of postoperative choroidal detachment]. / Kontrollierte Trabekulektomie und Häufigkeit der postoperativen Aderhautamotio.

In this study the authors report their experience with titrated trabeculectomy. It is performed as follows: tight scleral flap trabeculectomy, five or more 10/0 nylon sutures, argon laser lysis of one or more sutures (depending on the eye's postoperative condition) by means of the Hoskins lens. The aim of this technique, performed by the authors for 3 years, is to decrease atalamia and choroidal detachment. Results obtained in 70 eyes of 62 patients with chronic open-angle glaucoma are compared by means of statistical analysis with those in 70 eyes of 66 patients operated on by means of the traditional technique. The incidence of choroidal detachment is significantly reduced (P < 0.001). There is no important difference in ocular pressure and visual acuity. In conclusion, this technique is very useful in controlling and titrating the filtration rate, avoiding an excessive lowering of IOP after trabeculectomy and decreasing the complications.

MRI and intraocular tamponade media.

Thirteen patients who underwent surgery for retinal detachment and injection of intraocular tamponade media (silicone oil, fluorosilicone oil, or perfluorocarbon liquid) underwent magnetic resonance imaging (MRI), using spin-echo T1- and T2-weighted images. The ophthalmic tamponade media showed different signal intensity, according to their chemical structure. Unlike ophthalmoscopy or ultrasonography, MRI showed no oil-related artefact, making possible recognition of recurrent retinal detachment.