Nuclear and magnetic spin structure of the antiferromagnetic triangular lattice compound LiCrTe2 investigated by [Formula: see text]SR, neutron and X-ray diffraction.

Two-dimensional (2D) triangular lattice antiferromagnets (2D-TLA) often manifest intriguing physical and technological properties, due to the strong interplay between lattice geometry and electronic properties. The recently synthesized 2-dimensional transition metal dichalcogenide LiCrTe[Formula: see text], being a 2D-TLA, enriched the range of materials which can present such properties. In this work, muon spin rotation ([Formula: see text]SR) and neutron powder diffraction (NPD) have been utilized to reveal the true magnetic nature and ground state of LiCrTe[Formula: see text]. From high-resolution NPD the magnetic spin order at base-temperature is not, as previously suggested, helical, but rather collinear antiferromagnetic (AFM) with ferromagnetic (FM) spin coupling within the ab-plane and AFM coupling along the c-axis. The value if the ordered magnetic Cr moment is established as [Formula: see text]. From detailed [Formula: see text]SR measurements we observe an AFM ordering temperature [Formula: see text] K. This value is remarkably higher than the one previously reported by magnetic bulk measurements. From [Formula: see text]SR we are able to extract the magnetic order parameter, whose critical exponent allows us to categorize LiCrTe[Formula: see text] in the 3D Heisenberg AFM universality class. Finally, by combining our magnetic studies with high-resolution synchrotron X-ray diffraction (XRD), we find a clear coupling between the nuclear and magnetic spin lattices. This suggests the possibility for a strong magnon-phonon coupling, similar to what has been previously observed in the closely related compound LiCrO[Formula: see text].

Cervical Human Papillomavirus genotypes in HIV-infected women: a cross-sectional analysis of the VALHIDATE study.

INTRODUCTION: Primary-prevention by prophylactic vaccination against HPV-related cancers and HPV-based screening programs are based on HPV-type distribution in immunocompetent individuals. HIV-infected women are at high risk of invasive HPV-disease sustained by a broader range of HPV-types and have higher multi-type infection rates than immunocompetent hosts. METHODS: This is a cross-sectional analysis of High Risk HPV (HR HPV) type distribution in 805 HIV+ women (HIW) compared with a control group of 1402 immunocompetent HIV- women (SPW) enrolled in the VALHIDATE study in order to define HPV type-specific distribution according to cytology. RESULTS: HIW had a 3.8, 3.6, and 2.7 times higher risk of atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL) and high grade squamous intraepithelial lesion (HSIL) than SPW respectively. HPV-DNA prevalence was 28.4% in HIW and 11.81% in SPW (p<0.0001). The prevalence of infection increased from normal cytology to HSIL both in HIW (from 21.45% to 90.91%) and SPW (from 9.54% to 75%). The OR for women with normal cytology of having a positive HPV-DNA test result of was 2.6 times higher in HIW than in SPW. The cumulative prevalence of HPV-16/18 in HSIL is much lower in HIW (36.4±28.4) than SPW (62.5±33.5). CONCLUSIONS: A higher prevalence of infection and broader HPV type distribution were observed in HIV+ women compared to the general population. More than 60% of HSIL lesions of HIW patients are caused by single or multi-type infections from non-HPV16/18 HPVs. The potential 9v-HPV vaccine coverage could be even higher than that expected for the general population given the wide panel of HPV-types observed in the HSIL of HIV+ women.

A 3-week feed restriction after weaning as an alternative to a medicated diet: effects on growth, health, carcass and meat traits of rabbits of two genotypes.

Feed restriction after weaning is widely used in meat rabbit farms to promote health and reduce mortality, but this practice impacts negatively on rabbit growth and slaughter performance. This study compared a 3-week post-weaning feed restriction with ad libitum medicated feeding, evaluating effects on feed intake, growth, health, carcass and meat quality of rabbits of two genotypes: Italian White pure breed and Hycole hybrid×Italian White crossbred. A total of 512 rabbits at 36 days of age, of both sexes and two genotypes, were divided into four homogeneous groups assigned, from 36 to 57 days of age, to different feeding programmes (FP): restricted non-medicated (R-N), ad libitum non-medicated (L-N), restricted medicated (R-M) and ad libitum medicated (L-M). The diets were medicated with oxytetracycline (1540 mg/kg) and colistin sulphate (240 mg/kg). The restriction, performed by giving 70, 80 and 90 g/day of feed for the 1st, 2nd and 3rd week, was followed by ad libitum feeding in the successive 5 weeks, up to slaughter at 92 days of age. Restricted feeds were ingested at a level of 64% of the feed intake recorded in the ad libitum fed rabbits; it was significantly associated, regardless of medication and rabbit genotype, with a lower feed intake (-22 to -24 g dry matter/day) during the entire experiment, compensatory growth and a lower feed conversion ratio in the ad libitum period, and a lower final live weight (-150 g) than ad libitum feeding (P<0.001). During restriction, mortality was lower in the restricted rabbits (6.25%, 5.47% v. 12.5%, 14.8% for R-N, R-M, L-N and L-M; P<0.05), whereas in the ad libitum period mortality did not differ among the groups (9.23%, 9.90%, 11.0% and 4.59% for R-N, R-M, L-N and L-M). Dressing out percentage was not affected by FP or genotype; heavier carcasses were produced by rabbits fed ad libitum (+100 g; P<0.001) and crossbred rabbits (+122 g; P<0.001). Restriction did not alter meat quality, except for a tendency towards a higher cooking loss and less fat; crossbred meat was higher in L* (+1.3; P<0.01) and b* (+0.51; P<0.05) colour indexes and tenderness (-0.14 kg/cm2; P<0.05) than pure breed meat. Under the conditions of this study, a 3-week restricted feeding after weaning resulted to be a suitable alternative, also for high growth potential genotypes, to the antibiotics to preserve rabbit health. The production of lighter carcasses could be compensated partly by the lower feed conversion ratio showed by restricted rabbits.

HPV genotypes detected in the oropharyngeal mucosa of HIV-infected men who have sex with men in Northern Italy.

The aim of this study was to investigate the epidemiological profile of HPV oropharyngeal infections in HIV-infected men who have sex with men. A total of 135 subjects were enrolled at the L. Sacco University Hospital (Milan, Italy) to evaluate their HPV oropharyngeal infection status at baseline and at a follow-up visit at least 12 months later. HPV DNA was detected from oropharyngeal swabs using an in-house nested PCR that amplifies a segment of the L1 gene. The PCR products were then sequenced and genotyped. A greater percentage of high-risk genotypes was identified compared to low-risk genotypes (13·7% vs. 6·9%, P < 0·05), and two uncommon alpha-HPV genotypes were detected, i.e. HPV-102 and HPV-114. HPV infection prevalence was 24·4% and the cumulative incidence was 24·1%. During the follow-up period, one case of HPV infection (HPV-33) persisted, while the overall rate of infection clearance was 58·3%. HPV oropharyngeal infection was widespread in the cohort examined, and most of the infections were transient and cleared within 12 months. These results may help to clarify the role of HPV in the oropharynx and may also improve our understanding of the need to implement preventive strategies in at-risk populations.

Effects of ewes grazing sulla or ryegrass pasture for different daily durations on forage intake, milk production and fatty acid composition of cheese.

Sulla (Sulla coronarium L.) forage is valued for its positive impact on ruminant production, in part due to its moderate content of condensed tannin (CT). The duration of daily grazing is a factor affecting the feed intake and milk production of ewes. In this study, the effects of grazing sulla pasture compared with annual ryegrass, and the extension of grazing from 8 to 22 h/day, were evaluated with regard to ewe forage intake and milk production, as well as the physicochemical properties and fatty acid (FA) composition of cheese. During 42 days in the spring, 28 ewes of the Comisana breed were divided into four groups (S8, S22, R8 and R22) that grazed sulla (S) or ryegrass (R) for 8 (0800 to 1600 h) or 22 h/day, and received no feeding supplement. In six cheese-making sessions, cheeses were manufactured from the 48 h bulk milk of each group. Compared with ewes grazing ryegrass, those grazing sulla had higher dry matter (DM) intake, intake rate and milk yield, and produced milk that was lower in fat and higher in casein. Ewes grazing for 22 h spent more time eating, which reduced the intake rate, increased DM and nutrient intake and milk yield, and reduced milk fat. Due to the ability of CT to inhibit the complete ruminal biohydrogenation of polyunsaturated fatty acids (PUFA), the FA composition of sulla cheese was more beneficial for consumer health compared with ryegrass cheese, having lower levels of saturated fatty acids and higher levels of PUFA and n-3 FA. The FA profile of S8 cheese was better than that of S22 cheese, as it was higher in branched-chain FA, monounsaturated FA, PUFA, rumenic acid (c9,t11-C18:2), and had a greater health-promoting index. The effect of short grazing time on sulla was attributed to major inhibition of PUFA biohydrogenating ruminal bacteria, presumably stimulated by the higher accumulation of sulla CT in the rumen, which is related to a higher intake rate over a shorter eating time. Thus, grazing sulla improved the performance of ewes, thereby increasing, especially with short grazing time, the nutritional properties of cheese fat.

Effect of farming system and cheesemaking technology on the physicochemical characteristics, fatty acid profile, and sensory properties of Caciocavallo Palermitano cheese.

Caciocavallo Palermitano is a typical stretched-curd cheese that has been produced over the centuries in Sicily according to traditional cheesemaking technology and using raw milk from autochthonous cow breeds reared at pasture. The objective of this experiment was to evaluate the effects of the farming system and processing technology on the characteristics of Caciocavallo Palermitano cheese, with particular regard to the fatty acid profile. The farming system was either extensive, using autochthonous cows fed a pasture-based diet, or intensive, with specialized dairy cow breeds fed mainly hay and concentrate. The cheese-processing technology was either artisanal, using traditional wooden tools and endemic lactic bacteria, or advanced, using modern steel equipment and selected lactic bacteria. Twelve Caciocavallo Palermitano cheeses, 3 from each of the 4 experimental theses (2 farming systems × 2 cheesemaking technologies), were obtained and aged for 1, 30, 60, and 120 d. Milk of origin and cheeses were analyzed for the main chemical and rheological parameters. Fatty acids were methylated in lyophilized cheese and analyzed by gas chromatography. Sensory analysis was carried out by trained panelists. The PROC GLM of SAS 9.1.2 (SAS Institute Inc., Cary, NY) was used for the statistical analysis. The physical, chemical, and sensory characteristics of Caciocavallo Palermitano cheese were influenced more by the farming system than by the cheesemaking technology. Compared with cheese produced through intensive farming, cheese from extensive farming was richer in polyunsaturated, n-3, and odd- and branched-chain fatty acids, as well as in conjugated linoleic acid (cis-9,trans-11 C18:2), with accompanying improved human health benefits. The cheesemaking technology produced variation in the evolution of proteolysis during aging, due presumably to the different active microflora, which influenced the sensory profile of the resulting cheese. Indeed, cheese produced by artisanal manufacturing was described as less "bitter" and more "piquant" than cheese produced through the advanced process.

Relationship between body mass index, age and hypoxemia in patients with extremely severe obesity undergoing bariatric surgery.

BACKGROUND: Morbid obesity is frequently accompanied by serious co-morbidity, enclosed obstructive sleep apnea and hypoventilation syndrome, and thus many morbidly obese patients require surgical interventions. The aim of this study was to evaluate the relationship between arterial oxygen (pO2) and carbon dioxide (pCO2) partial pressure, age, loss of excess weight, and body mass index (BMI) in obese patients scheduled to undergo bariatric surgery. PATIENTS AND METHODS: A group of 11 patients (4 men, 7 women, median age 38 years, range 23-58 years) with extremely severe obesity (BMI>50 kg/m²) underwent laparoscopic Roux-en-Y gastric bypass. Preoperatively, BMI, pO2, and pCO2 were 52.7±2.4 kg/m², and 70.9±5.3 and 43.1±6.5 mmHg, respectively. Hypoxemia (pO2<75 mmHg) was present in all patients, but no relationship between BMI and age (R=-0.24, p=0.44) or between BMI and pO2 (R=0.09, p=0.77) was found. RESULTS: As expected, there was a significant correlation between age and both pO2 (R=-0.58, p=0.04) and pCO2 (R=0.85, p=0.0004), while no relationship between BMI and age (R=-0.24, p=0.44), nor between BMI and pO2 (R=0.09, p=0.77) was found. Finally, there was a significant correlation between pO2 and loss of excess weight (R=-0.69, p=0.02). No intra- or postoperative complications were observed, and 12 months after surgery BMI decreased to 32.5±2.7 kg/m² (p<0.001) and pCO2 to 37.9±5.3 mmHg (p=0.05), while pO2 reached 85.8±6.8 (p<0.001) mmHg. CONCLUSIONS: In obese patients, the severity of hypoxemia is mainly related to age. The amount of weight reduction, rather than lower baseline BMI values, may justify the significant postoperative pO2 improvement.

Interferon-gamma releasing assay versus tuberculin skin testing for latent tuberculosis infection in targeted screening programs for high risk immigrants.

BACKGROUND: Recent immigrants from developing countries (<2 years since immigration) are at very high risk of active TB disease due to reactivation of latent infections acquired in the country of origin. In industrialized low-incidence TB countries targeted testing programs for high risk groups could allow the detection of latently infected persons who would likely benefit from a course of preventive treatment. In this study we evaluated the tuberculin skin test (TST) and interferon-gamma enzyme-linked immunosorbent assay (QuantiFERON TB-gold in tube, QFT-IT) strategies for TB infection screening programs in recent immigrants from highly endemic countries. PATIENTS AND METHODS: This is a prospective cross-sectional study. Paired tests performed in 1,130 immigrants attending an outpatient ward, between 2005 and 2007 for any health problem were evaluated by intention-to-treat (ITT) and per-protocol (PP) analysis for efficiency and efficacy of screening program. RESULTS: Positive TST and QFT-IT were observed in 36.04 versus 29.82% (ITT) and in 45.27 versus 30.22% (PP) respectively. A higher drop-out rate was observed for TST (20.35 vs. 1.33%) (p < 0.0001). Second level assessment was accepted by half of the TST positive patients. Overall agreement rate between 887 paired tests was fair (k = 0.38). Higher k values were observed for higher TB prevalence rate in the country of origin (k = 0.43), for TST induration diameters >20 mM (k = 0.47), in subjects aged 40-50 years (k = 0.41) and in unvaccinated persons (k = 0.40). In a multiple logistic regression model continent of origin, class of TB prevalence in the country of origin and contacts with TB patients were found to be significantly associated with the probability of TST and QFT-IT positive result. Low education levels were associated only to an increased risk of TST positive results. CONCLUSIONS: The drawback of the TST screening strategy in recent immigrants from highly endemic countries is due to low sensitivity/specificity of the test and to high drop-out rate with an overall significant lowering in strategy efficacy/efficiency. The higher QFT-IT specificity prevents unnecessary overload of the health care system and, although more expensive, might represent a cost-effective alternative to TST in targeted screening programs directed to high risk populations.

Pre-emptive treatment of acute GVHD: a randomized multicenter trial of rabbit anti-thymocyte globulin, given on day+7 after alternative donor transplants.

We have previously shown that hemopoietic stem cell transplant (HSCT) recipients can be stratified on day+7 as having low, intermediate or a high risk of transplant-related mortality (TRM). With the aim of reducing TRM and GVHD, intermediate and high-risk patients (n=170) were randomized to receive anti-thymocyte globulin (ATG, thymoglobuline) on day+7 (n=84) or no treatment (n=86) (controls). There was a reduction of TRM from 35% in controls to 29% in ATG patients (P=0.3), of acute GVHD III-IV from 15 to 5% (P=0.02) and of chronic GVHD from 26 to 11% (P=0.03); survival was comparable. The predictive value of the day+7 score on TRM was confirmed for controls (19 vs 42% for intermediate vs high risk, respectively, P=0.03), whereas ATG abrogated this predictive effect (29 vs 29%). ATG reduced GVHD (P=0.006) in high-risk patients, but not in patients with an intermediate risk. In conclusion, we confirm that TRM can be predicted on the basis of day+7 laboratory values, after alternative donor HSCT; in high-, but not intermediate-risk patients, the administration of ATG on day+7 reduces GVHD. These results may represent a platform for risk-adapted post transplant immune modulation.

The effects of different milking intervals and milking times per day in jennet milk production.

In their first 150 days of lactation, nine Ragusana jennets were investigated at the 'Istituto Sperimentale Zootecnico per la Sicilia' (ISZS) in Palermo, to study the effects of different milking typologies on milk production. The jennets were kept in a paddock and were fed hay ad libitum and concentrate (3.5 kg jennet/day). From post-foaling day 21, every 3 weeks individual milk amounts were recorded, and individual milk samples were collected and analyzed for the main qualitative parameters. The compared theses were: two daily milking times with 6- and 3-h intervals; and two, three and eight daily milking times with 3-h interval. The jennets were manually milked. The foals were separated from the jennets at 0800 h, and after the last milking the foals were housed with the jennets. During the day with eight milkings, the milk yield from the jennets was fed to their respective foals, through bottles. The 6-h milking interval produced more milk (+19%) per session than the 3-h interval (P 0.01). The fat content per session, with the eight-time milking frequency (P 0.001), was greater than the others. For each milking typology, the lactation stage had a similar effect on almost all the considered variables. When observing the eight-milking times, the fat content (%) increased from 1100 to 0500 h (P 0.001). The milk yield and the fat percentage produced by two-, three- and eight-milking times were positively correlated.

Increased formation of 8-iso-prostaglandin F(2alpha) is associated with altered bone metabolism and lower bone mass in hypercholesterolaemic subjects.

OBJECTIVES: To investigate the relationship of 8-iso-prostaglandin (PG) F(2alpha) levels, a reliable marker of in vivo oxidative stress and lipid peroxidation, with bone mineral density (BMD), bone turnover markers, osteoprotegerin (OPG) and receptor activator of nuclear factor-kappa B ligand (RANKL) in hypercholesterolaemia. DESIGN: Cross-sectional study. SETTING: University hospital centre. METHODS: Serum 8-iso-PGF(2alpha) levels were measured in 173 hypercholesterolaemic subjects and in 152 age- and sex-matched normocholesterolaemic controls. Femoral neck and lumbar spine BMD, serum bone-specific alkaline phosphatase (BAP), osteocalcin (OC), OPG and RANKL levels, as well as urinary levels of C-terminal telopeptides of type I collagen (CTX-I), were also assessed. RESULTS: Hypercholesterolaemic subjects showed higher (P < 0.0001) serum 8-iso-PGF(2alpha) levels than controls. They also had decreased (P < 0.0001) femoral neck and lumbar spine BMD, and lower (P < 0.0001) serum BAP and OC levels. No significant differences between hypercholesterolaemic and control subjects were found when comparing urinary CTX-I levels, or serum OPG and RANKL levels. In multivariate linear regression analysis, serum 8-iso-PGF(2alpha) was the only negative predictor for femoral neck BMD and serum BAP and OC levels in hypercholesterolaemic subjects. No significant correlation (all P > 0.25) was present between serum 8-iso-PGF(2alpha) levels and urinary CTX-I levels, or serum OPG and RANKL levels, in hypercholesterolaemic subjects. CONCLUSIONS: We found an association between increased serum 8-iso-PGF(2alpha) levels and lower bone mass and reduced serum BAP and OC concentrations in hypercholesterolaemic subjects. These results would suggest a possible role for oxidative stress in the development of lower bone mass in hypercholesterolaemia.

Conformationally constrained analogues of endogenous tripeptide inhibitors of zinc metalloproteinases.

Two diastereomeric furan-2-carbonylamino-3-oxohexahydroindolizino[8,7-b]indole carboxylates, highly constrained analogues of endogenous pyroglutamyl tripeptide inhibitors of snake venom endopeptidases, have been prepared as potential inhibitors of adamalysin II and matrix metalloproteinases. They proved to be inactive against adamalysin II and weak inhibitors of gelatinase A, gelatinase B, stromelysin 1 and human neutrophil collagenase. Evaluation of the mode of binding of the (2R,5S,11bR) isomer in the active site of adamalysin II suggests that the decrease of potency may be due to the reorientation of the acylamino chain in three of the heterocyclic nucleus, to a short contact at the entrance of the S'(1) hydrophobic cleft and to the loss of flexibility of the tetracyclic nucleus in the P'(1), P'(2) region of the inhibitor, which prevents optimal arrangement in the S'(1) specificity subsite.

Extended form of a retro-inverso peptide stabilized by beta-sheet unidirectional H-bonds: Crystallographic and NMR evidence.

The crystallographic investigation of the retro-inverso peptide Bz-S-gAla-R-mAla-NHPh reveals an extended backbone conformation where the NH groups of the gem-diamino alkyl moiety and the CO groups of the malonyl residue face side by side. This extended conformation, presenting all carbonyls on opposite sides of the NH groups, is stabilized by interstrand H-bonds running in a single direction of the parallel beta-sheets that characterize the crystal packing. These sheets differ from the beta-sheets formed by native amino acids only. (1)H-NMR nuclear Overhauser effect spectroscopy (NOESY) experiments suggest that a conformation similar to that found in the crystal also prevails in dimethylsulfoxide solution. Previous potential energy calculations of gem-diamino alkyl (g) and malonyl (m) Ala residues predicted that extended forms were less stable than the helical ones because of strong electrostatic repulsions between the parallel polar groups. Similar arguments were invoked to give more weight to helical forms of the retro-peptide units in the proposal of packing models of some nylons in their crystalline polar regions. The present findings show that both g and m Ala residues can experience the extended conformation in the beta-sheet aggregation. The energy increase occurring in one strand, due to the parallel orientation of consecutive peptide dipoles, is more than compensated by favorable cooperative interactions among head-to-tail aligned peptide dipoles of facing strands, resulting in the formation of two C==O...H==N H-bonds per residue.

Two crystal structures of human neutrophil collagenase, one complexed with a primed- and the other with an unprimed-side inhibitor: implications for drug design.

Two crystal structures of human neutrophil collagenase (HNC, MMP-8), one complexed with a primed- and the other with an unprimed-side inhibitor, were determined using synchrotron radiation at 100 K. Both inhibitors contain non-hydroxamate zinc-binding functions. The Pro-Leu-L-Trp(P)(OH)(2) occupies the unprimed region of the active site, furnishes new structural information regarding interaction between the catalytic zinc ion and the phosphonate group, and is the only example of occupation of the S(1) subsite of MMP-8 by the bulky tryptophan side chain. The (R)-2-(biphenyl-4-ylsulfonyl)-1,2,3, 4-tetrahydroisochinolin-3-carboxylic acid, a conformationally constrained D-Tic derivative, accommodates its biphenyl substituent into the deep primary specificity S(1)' subsite, inducing a widening of the entrance to this pocket; this modification of the protein, mainly consisting in a shift of the segment centered at Pro217, is observed for the first time in MMP-8 complexes. Cation-aromatic interactions can stabilize the formation of both complexes, and the beneficial effect of aromatic substituents in proximity of the catalytic zinc ion is discussed. The phosphonate group bound to either a primed- or unprimed-side inhibitor maintains the same relative position with respect to the catalytic zinc ion, suggesting that this binding function can be exploited for the design of combined inhibitors assembled to interact with both primed and unprimed regions of the active cleft.

Peptides containing the sulfonamide junction. 2. Structure and conformation of Z-Tau-Pro-D-Phe-NHiPr.

The taurine (Tau) containing N-protected pseudotripeptide isopropylamide Z-Tau-Pro-D-Phe-NHiPr (1) has been specifically designed and synthesized as suitable model to test the ability of the sulfonamido group to participate as H-bond acceptor to a type II beta-turn and to get information on the preferred rotameric conformation around the S-N bond and the hybridization state of the nitrogen atom. The present structural investigation reveals that, although the sulfonamide junction is invariably folded in a gauche mode, the beta-turn structure, stabilized by the 4 --> 1 hydrogen bond, is not found in the crystal and the sulfonamido oxygen atoms are not involved in any intra- or intermolecular hydrogen-bond interaction. More than one conformer populates the CDCl(3) solution with only a minor contribution by the expected beta-turn. The Pro nitrogen is significantly pyramidalized and the nitrogen lone pair points in opposite direction to that of the Pro C(alpha)H bond thus adopting R chirality, in an arrangement practically identical to that found in the previously studied homochiral analogue Z-Tau-Pro-Phe-NHiPr.

Inhibition of adamalysin II and MMPs by phosphonate analogues of snake venom peptides.

Phosphonate analogues of the peptidomimetic N-(Furan-2-yl)carbonyl-Leu-Trp-OH were prepared with the goal of evaluating the effect of phosphonate for carboxylate replacement on binding with snake venom metalloproteinases and MMPs. N-(Furan-2-yl)carbonyl-Leu-L-Trp(P)-(OH)2 showed a 75-fold increase of the inhibiting activity against adamalysin II, a snake venom metalloproteinase structurally related to MMPs and TACE. Both the phosphonate and carboxylate peptidomimetics fit into the active site adopting a retrobinding mode and provide the structural base for a new class of metalloproteinases inhibitors.

Shortened head-up tilt testing potentiated with sublingual nitroglycerin in patients with unexplained syncope.

BACKGROUND: Head-up tilt testing is extensively used to determine the vasovagal origin of syncope in patients with otherwise unexplained loss of consciousness, although issues remain regarding the method of the test. The diagnostic value of a shortened head-up tilt test potentiated with sublingual nitroglycerin was assessed in patients with unexplained syncope. METHODS: Two hundred two patients (mean age 49+/-19 years) with syncope of unknown origin and 34 subjects in a control group (mean age 45+/-17 years) were studied. The patients and the subjects in the control group were tilted upright to 60 degrees for 20 minutes. If syncope did not occur, sublingual nitroglycerin (400 microg) was administered, and observation was continued for 25 more minutes. RESULTS: During the unmedicated phase syncope occurred in 22 (11%) patients and in one member of the control group. After nitroglycerin was administered, syncope occurred in 119 (59%) patients and in 1 (3%) member of the control group. False-positive response (exaggerated response) was observed in eight (4%) patients and in four (12%) subjects in the control group. The total positivity rate of the test was 70% with a specificity rate of 94%. CONCLUSIONS: Short-duration head-up tilt test potentiated with sublingual nitroglycerin provides an adequate specificity and positivity rate in patients with unexplained syncope.

Pheochromocytoma crisis caused by contemporary ergotamine, caffeine, and nimesulide administration.

Pheochromocytoma is a rare tumor that secretes excess catecholamines. Pheochromocytoma crises may be precipitated by the use of several drugs. This article describes the case of a patient affected by pheochromocytoma in whom multiple organ failure developed after contemporary administration of ergotamine, caffeine, and nimesulide. The patient recovered completely long after surgical intervention.

Synthesis, conformation, and biological activity of two fMLP-OMe analogues containing the new 2-[2'-(methylthio)ethyl]methionine residue.

The new C alpha-tetrasubstituted alpha-amino acid residue 2-[2'-(methylthio)ethyl]methionine (Dmt) has been introduced into the reference chemotactic tripeptide HCO-Met-Leu-Phe-OMe (fMLP-OMe) in place of the leucine or methionine, respectively. The biological activity of the new analogues [Dmt2]fMLP-OMe (2) and [Dmt1]fMLP-OMe (3) has been determined; whereas 2 is active toward human neutrophils, stimulating directed migration, superoxide anion generation, and lysozyme release, 3 results practically inactive in all tested assays. A conformational analysis on 2 and 3 has been performed in solution by using ir absorption and 1H-nmr. The conformation of 2 was also examined in the crystal by x-ray diffraction methods. Both 2 and 3 adopt fully extended conformation in correspondence with the Dmt residue. Biological and conformational results are discussed and compared with related previously studied models.