Value of IL28B genotyping in patients with HCV-related mixed cryoglobulinemia: results of a large, prospective study.

HCV-related mixed cryoglobulinemia (MC) is characterized by clonal expansion of B cells producing a polyreactive natural antibody (rheumatoid factor) and interferon (IFN)-based therapy is the first therapeutic option in mild-moderate MC. Single nucleotide polymorphisms (SNPs) proximal to genes involved in the innate response (IL28B/IFN-λ gene family) are strongly associated with spontaneous and IFN-induced viral clearance in hepatitis C, but no data exist about their role in HCV-positive MC. A large cohort of patients with HCV and MC was studied to evaluate the influence of IL28B genotype on the response to treatment and/or the evolution to MC of HCV infection. The rs12979860/rs8099917 IL28B polymorphisms were analysed in 481 consecutive HCV-positive subjects (250 with MC and 231 without MC, as controls) using real-time PCR and direct sequencing. Hundred and fifteen HCV patients with MC received standard anti-HCV therapy, and the results were evaluated according to the IL28B SNP distribution. Similar IL28B SNPs allele frequencies were recorded for patients and controls. IL28B major allele homozygosis (for both SNPs tested) was tightly correlated with virological and clinical response (P = 0.002). A statistically significant association was limited to 'difficult-to-treat' (G1/4) HCV genotypes. The IL28B genotype was a strong independent predictor of response (P = 0.007, OR 6.06; CI 1.65-22.22). The IL28B genotype was confirmed to be a useful predictor of response to IFN-based therapy in patients with HCV and MC. The very close correlation between IL28B SNP distribution, virological and clinical response definitively confirmed the key role played by HCV in MC. Conversely, the IL28B genotype does not seem to influence the evolution to MC.

Transmittance Fourier transform infrared spectra of liquid water in the whole mid-infrared region: temperature dependence and structural analysis.

Transmittance Fourier transform infrared (FT-IR) spectra of liquid water in the 4-80 degrees C temperature range are reported in the whole mid-infrared (MIR) region (4000-360 cm (-1)). The spectra were recorded by using a newly developed, home-made transmittance cell, working in light vacuum conditions (pressures of the order of 3-4 millibar). This permits the elimination of the aqueous vapor bands from the liquid spectra, particularly in the bending region, and the rapid collection of data without fluxing large amounts of nitrogen through the interferometer sample chamber. The temperature evolution of the OH stretching and HOH deformation bands is discussed in terms of Gaussian components analysis and a two-state model describing the equilibrium between different H-bond structures of liquid water. From this picture, structural and thermodynamic information about the hydrogen-bonding network of water is obtained.

Vascular damage and not hypertension per se influences endothelin-1 plasma levels in patients with non insulin dependent diabetes mellitus.

Several reports indicate higher endothelin-1 (ET-1) levels in patients with non insulin dependent diabetes mellitus (NIDDM), although this finding has not been confirmed by other studies. The discrepancy may be partially explained by the frequent coexistence in NIDDM patients of other pathologies, such as essential hypertension, and by the presence of diabetic vascular complications or renal failure, able, per se, to increase ET-1 circulating levels. This study aimed to evaluate the influence of arterial hypertension and/or of diabetic angiopathy on ET-1 circulating levels in a group of NIDDM patients. We measured ET-1 plasma concentrations in three groups of subjects: a) 22 NIDDM patients with or without hypertension and with or without vascular complications; b) 11 hypertensive patients; c) 14 age-matched healthy volunteers. Plasma ET-1 concentrations were significantly higher in NIDDM patients with angiopathy (7.3 +/- 0.7 pg/ml, mean +/- Standard Error; p < 0.001) than diabetics without angiopathy (4.4 +/- 0.53 pg/ml), hypertensive patients (4.7 +/- 0.85 pg/ml) and healthy subjects (3.1 +/- 0.19 pg/ml). This report indicates that increased plasma ET-1 levels in NIDDM patients may be ascribed only to those with vascular compliances, while hypertension, per se, does not affect ET-1 plasma levels in these patients.

Serum beta-endorphin increase after intravenous histamine treatment of chronic daily headache.

Histamine is able to induce spontaneous-like headache attacks in migraine and cluster headache subjects. Therefore, it has been considered as a possible agent in the pathogenesis of headache. Histamine desensitization is used for the treatment of cluster and other chronic headaches like migrains with interparoxysmal headache. However, it is unknown whether desensitization plays a role in headache improvement. Since a disfunction of the opioid system has been considered responsible for idiopathic headache and since low beta-endorphin levels have been demonstrated in some idiopathic headaches, particularly in migraine with interparoxysmal headache, we planned this study to verify if histamine therapy is able to modify serum beta-endorphin concentrations. For this purpose, we studied 24 healthy control subjects and 36 patients suffering from migraine with interparoxysmal headache refractory to conventional therapies. Patients showed baseline serum beta-endorphin levels significantly lower than healthy control subjects and treatment with histamine for 15 days increased their beta-endorphin concentrations. We believe that histamine treatment can activate the opioid endogenous system. However, the therapeutic effect of histamine remains to be verified by evaluating the correlation between beta-endorphin levels and headache improvement.

Evidence for bone mass and body fat distribution relationship in postmenopausal obese women.

The measurement of bone mass, a reliable predictor of osteoporotic fractures, in obese subjects has yielded conflicting results and bone mass has been reported to be elevated, normal or decreased. These observations indicate that factors other than body weight may be involved in the less risk for osteoporosis in obese subjects. In order to clarify the role of body fat distribution on bone density we studied sixty postmenopausal overweight/obese women with Body Mass Index (BMI) over 25 kg/m(2). Thirty five age-matched, nonobese postmenopausal women, served as controls. Bone mineral density (BMD) was measured at the proximal and ultradistal non dominant forearm using a double energy X-ray absorption (DEXA) apparatus. The waist/hip circumferences ratio (WHR) was used, in obese group, as an anthropometric estimation of the abdominal (WHR>0.85) to lower-extremity (WHR>0.85) fat proportion. The results were analyzed by Student t-test, ANOVA, and multiple linear regression analysis. No difference was found in BMD between obese group and controls, but a highly significant (P<0.001) positive correlation has been documented between proximal and ultradistal radius bone mineral density and waist/hip ratio in the obese group. Instead not significant correlation was found with BMI. Regional fat topography may influence the bone mass independently of total adiposity and visceral fat was the primary parameter accounting for higher bone mineral density values. These finding suggest that women with android-like obesity are protected from osteoporosis.

Serum osteocalcin levels in postmenopausal obese women.

In epidemiology of osteoporosis, obesity is to be considered one of its protecting factors. However there are in the literature discordant opinions: some authors describe a protective effect of obesity on the trabecular bone, others on the cortical one, others no effects at all and others finally a positive influence on both the trabecular and the cortical bone. However, only few studies on obesity's impact on bone metabolism are available. Bone mineral density at forearm and serum osteocalcin levels, a specific and sensitive marker of bone turn-over, in a group of postmenopausal obese women with those of a nonobese control group were compared. Obese women showed higher densitometric measurements than nonobese, but only the values of the third distal site of forearm resulted higher in a significant way. Serum osteocalcin values were similar between the two groups but the obese women showed a greater dispersion of the values (8.15 +/- 4.96 ng/ml) compared to nonobese (8.35 +/- 1.63 ng/ml). This high variability suggests an heterogeneity of bone turn-over in obese subjects and could explain the discordant results of the literature.

Angiopathy affects circulating endothelin-1 levels in type 2 diabetic patients.

To evaluate the role of endothelin-1 (ET-1), a vasoconstrictor and mitogenic peptide synthesized by endothelial cells, on the endothelial dysfunction in non-insulin-dependent diabetic (type 2) patients, we have measured the circulating ET-1 levels in 25 patients with and without clinically evident vascular complications and in a control group. Circulating ET-1 levels were significantly higher in diabetic patients with angiopathy than in diabetics without angiopathy and in controls (7.02 +/- 2.9 pg/ml vs 4.4 +/- 1.1 pg/ml and 3.08 +/- 0.7 pg/ml, respectively; P < 0.001). No difference was demonstrated between diabetic patients without angiopathy and controls. These findings suggest that ET-1 may be a marker for arterial vascular disease only in patients with overt angiopathy. It is unclear whether it participates in the endothelial injury process or it is merely released from damaged endothelial cells.

Serum melatonin in multiple myeloma: natural brake or epiphenomenon?

Melatonin (MEL), the main hormone produced by the pineal gland, seems to exert antineoplastic activity both in vitro and in vivo. Moreover, several studies reported increased melatonin blood levels in cancer patients. Plasma melatonin concentrations were determined in 46 patients with multiple myeloma and in 31 age matched healthy subjects (57.8 +/- 6.9 versus 55.2 +/- 8.9 years). Venous blood was drawn between 7.30 and 9.30 a.m. and melatonin was assayed using a commercially available radioimmunoassay. The data were analysed by Student's t test and results reported as mean values +/- standard deviation. The patients with multiple myeloma showed significantly higher mean melatonin serum levels than healthy subjects (21.6 +/- 13.5 versus 12.1 +/- 4.8 pg/ml; p < 0.001). This behaviour could actually represent a phenomenon secondary to an altered endocrine-metabolic balance caused by an increased demand of the developing tumor. On the other hand, the increased melatonin secretion might be considered as a compensatory mechanism due to its antimitotic action and therefore as an effort to secrete substances capable of regulating neoplastic growth.

Comparison between venoconstrictor effects of sumatriptan and ergotamine in migraine patients.

The vasoconstrictor activity of sumatriptan and ergotamine were compared by injecting these drugs in the hand vein of migraine subjects. We used the "venotest method", which permits the evaluation of the venoconstrictor effect of small doses of drugs, acting locally in the hand vein. Sumatriptan injected at increasing doses in the hand vein provoked contraction only at high doses (500 micrograms): venoconstriction lasted 5-15 minutes and was similar in intensity and duration to that induced by 0.5-1 micrograms of 5-hydroxytryptamine (5-HT). Likewise, ergotamine induced contraction only at a dose of 50 micrograms: this venoconstrictor effect was long lasting (at least 1 hour). Ergotamine-induced hand vein contraction, almost completely inhibited by ketanserin, seems mediated at least in part by 5-HT2 receptors, like the one induced by 5-HT and sumatriptan, already observed in a previous study. Clinical doses of ergotamine (0.25 mg intramuscular) and of sumatriptan (6 mg subcutaneous) do not provoke hand vein contraction for at least 1 hour: this could be due to a low activity of these drugs on the 5-HT2 vein receptors or a technique that is unsuitable to detect the vasoconstrictor effect of drugs given by the systemic route. The long lasting venoconstrictor effect of ergotamine may be due to a slow dissociation from receptor sites. The short vasoconstriction induced by sumatriptan could account for the recurrence of headache in many sumatriptan-treated migraine subjects.