Testosterone-to-estradiol ratio and platelet thromboxane release in ischemic heart disease: the EVA project.

BACKGROUND: Data on the interplay between sexual hormones balance, platelet function and clinical outcomes of adults with ischemic heart disease (IHD) are still lacking. OBJECTIVE: To assess the association between the Testosterone (T)-to-Estradiol (E2) Ratio (T/E2) and platelet activation biomarkers in IHD and its predictive value on adverse outcomes. METHODS: The EVA study is a prospective observational study of consecutive hospitalized adults with IHD undergoing coronary angiography and/or percutaneous coronary interventions. Serum T/E2 ratios E2, levels of thromboxane B2 (TxB2) and nitrates (NO), were measured at admission and major adverse events, including all-cause mortality, were collected during a long-term follow-up. RESULTS: Among 509 adults with IHD (mean age 67 ± 11 years, 30% females), males were older with a more adverse cluster of cardiovascular risk factors than females. Acute coronary syndrome and non-obstructive coronary artery disease were more prevalent in females versus males. The lower sex-specific T/E2 ratios identified adults with the highest level of serum TxB2 and the lowest NO levels. During a median follow-up of 23.7 months, the lower sex-specific T/E2 was associated with higher all-cause mortality (HR 3.49; 95% CI 1.24-9.80; p = 0.018). In in vitro, platelets incubated with T/E2 ratios comparable to those measured in vivo in the lowest quartile showed increased platelet activation as indicated by higher levels of aggregation and TxB2 production. CONCLUSION: Among adults with IHD, higher T/E2 ratio was associated with a lower long-term risk of fatal events. The effect of sex hormones on the platelet thromboxane release may partially explain such finding.

Nanoscale x-ray investigation of composition fluctuations in AlGaN nanowires.

In the present study we combined, in the same synchrotron x-ray experiment, reciprocal space mapping, multiwavelength anomalous diffraction and diffraction anomalous fine structure, to determine the strain, crystallographic polarity, alloy composition and ordering at the atomic scale in [0001]-oriented AlGaN nanowires grown by molecular beam epitaxy on GaN nanowire bases. The information that we obtained was averaged over a macroscopic ensemble of NWs. We found from the diffraction anomalous fine structure that there were an isotropic increased number of Ga-Ga pairs in the Ga next nearest coordination shell (cation sublattice) with respect to what is expected for the AlGaN alloy composition determined by anomalous diffraction. This significant deviation from random alloy atomic distribution is present whatever the AlN molar fraction and growth conditions. Our results are consistent with nanoscale composition fluctuations expected from both alloy disorder or kinematically driven spontaneous ordering, both effects being suspected to account for the physical properties of AlGaN ternary alloys.

Comparison of bleeding risk scores in patients with atrial fibrillation: insights from the RE-LY trial.

BACKGROUND: Oral anticoagulation is the mainstay of stroke prevention in atrial fibrillation (AF), but must be balanced against the associated bleeding risk. Several risk scores have been proposed for prediction of bleeding events in patients with AF. OBJECTIVES: To compare the performance of contemporary clinical bleeding risk scores in 18 113 patients with AF randomized to dabigatran 110 mg, 150 mg or warfarin in the RE-LY trial. METHODS: HAS-BLED, ORBIT, ATRIA and HEMORR2 HAGES bleeding risk scores were calculated based on clinical information at baseline. All major bleeding events were centrally adjudicated. RESULTS: There were 1182 (6.5%) major bleeding events during a median follow-up of 2.0 years. For all the four schemes, high-risk subgroups had higher risk of major bleeding (all P < 0.001). The ORBIT score showed the best discrimination with c-indices of 0.66, 0.66 and 0.62, respectively, for major, life-threatening and intracranial bleeding, which were significantly better than for the HAS-BLED score (difference in c-indices: 0.050, 0.053 and 0.048, respectively, all P < 0.05). The ORBIT score also showed the best calibration compared with previous data. Significant treatment interactions between the bleeding scores and the risk of major bleeding with dabigatran 150 mg BD versus warfarin were found for the ORBIT (P = 0.0019), ATRIA (P < 0.001) and HEMORR2 HAGES (P < 0.001) scores. HAS-BLED score showed a nonsignificant trend for interaction (P = 0.0607). CONCLUSIONS: Amongst the current clinical bleeding risk scores, the ORBIT score demonstrated the best discrimination and calibration. All the scores demonstrated, to a variable extent, an interaction with bleeding risk associated with dabigatran or warfarin.

Sarcopenia and poor nutritional status in older adults.

BACKGROUND & AIMS: The association between sarcopenia and malnutrition has been poorly studied in the older population. The purpose of this study is to address the association between sarcopenia, according to different validated definitions, and nutritional status in a large population of community-dwelling older adults. METHODS: Observational, cross-sectional study of the Geriatric Frailty Clinic (GFC) for Assessment of Frailty and Prevention of Disability, held by the "Gérontopôle" of the Toulouse University Hospital. Patients aged above 65 years who benefitted from a Dual X-ray Densitometry (DXA) during their assessment at the GFC from June 5th 2013 to January 28th 2020 were included. Sarcopenia was defined according to proposed validated definitions. The Mini Nutritional Assessment (MNA) was used to stratify nutritional status, and identify patients with a poor nutritional status (at risk of malnutrition or malnourished, MNA <24). Multiple logistic regression analyses were performed between MNA and each sarcopenia definition adjusted for confounders. RESULTS: Among the 938 patients with DXA data, a total of 809 (86.2 %) subjects were included in the analysis (mean age 81.8 ± 6.9 years, 527 females (65.1 %)). Prevalence of sarcopenia ranged from 12.6 % to 44.9 %, according to various definitions. Overall 244 (30.2 %) of the patients had a poor nutritional status (MNA-score <24), Baumgartner and Newman definitions of sarcopenia were both associated with low MNA-scores (OR = 4.69, CI 3.15-6.98 and OR = 2.30, CI 1.55-3.14, respectively), EWGSOP2 "confirmed sarcopenia" definition was also associated with low MNA-scores (OR = 3.68, CI 2.30-5.89), as well as for the lean mass definition according EWGSOP2 cut-off (OR 5.22 CI 3.52-7.73). Both FNIH and EWGSOP2 "probable sarcopenia" definitions were not associated with the risk of malnutrition. CONCLUSIONS: In this study, the prevalence of sarcopenia ranged from 12.6 to 44.9 % according to various definitions. A score of MNA under 24, was associated with almost all of the sarcopenia definitions. This study reinforces the concept that malnutrition and sarcopenia are strictly related. When facing malnutrition in daily clinical practice, body composition should be assessed and the proposed nutritional intervention should be tailored by these results in order to prevent the onset of late-life disability.

Social Vulnerability, Frailty and Self-Perceived Health: Findings from The Irish Longitudinal Study on Ageing (TILDA).

BACKGROUND: Social vulnerability interacts with frailty and influences individuals' health status. Although frailty and social vulnerability are highly predictive of adverse outcomes, their relationship with self-perceived health(SPH) has been less investigated. METHODS: Data are from the Irish Longitudinal Study on Ageing(TILDA), a population-based longitudinal study of ageing. We included 4,222 participants aged ≥50 years (age 61.4±8.5 years;women 56%) from Wave 1 (2009-2011) followed over three longitudinal waves (2012,2014-2015,2016). Participants responded to single questions with five response options to rate their 1)physical health, 2)mental health, and 3)health compared to peers. 30-item Frailty (FI) and Social Vulnerability (SVI) indices were calculated using standardised methods. Multivariable regression analyses were performed to establish the association between FI and SVI cross-sectionally and longitudinally over 6 years. RESULTS: Cross-sectionally, SVI (mean:0.40±0.08; range:0.14-0.81) and FI (mean: 0.13±0.08; range:0.10-0.58) were modestly correlated (r=0.256), and independently associated with poor physical health (SVI: OR 1.43, 95%CI 1.15-1.78; FI: OR 3.16, 95%CI 2.54-3.93), poor mental health (SVI: OR 1.65, 95%CI 1.17-2.35; FI: OR 3.64, 95%CI 2.53-5.24), and poor health compared to peers (SVI: OR 1.41,95%CI 1.06-1.89; FI: OR 3.86, 95%CI 2.9-5.14). Longitudinally, FI and SVI were independently and positively associated with poor physical health (SVI: ß 1.08, 95%CI 0.76-1.39; FI: ß 1.97, 95%CI 1.58-2.36), poor mental health (SVI: ß 1.18, 95%CI 0.86-1.5; FI: ß 1.58, 95%CI 1.2-1.97), and poor overall health compared to peers (SVI: ß 0.78, 95%CI 0.89-1.33; FI: ß 1.74, 95%CI 0.47-1.1). CONCLUSIONS: In a large cohort of community-dwelling older adults, frailty and social vulnerability were associated with poor SPH and with risk of SPH decline over six years.

Effect of L-carnitine on oxidative stress and platelet activation after major surgery.

BACKGROUND: The surgical/anesthesia trauma is associated with an increased production of reactive oxygen species (ROS). This enhanced oxidative stress leads to cell damage resulting in various complications such as sepsis, myocardial injury and increased mortality. The aim of this study was to investigate the role of antioxidant treatment with l-carnitine in oxidative stress and platelet activation in patients undergoing major abdominal surgery. METHODS: Forty patients scheduled for abdominal surgery were randomly allocated to l-carnitine, administered with a rapid infusion (0.05 g/kg) diluted in 250 ml of saline solution, vs. placebo treatment just before the surgical intervention. At baseline and after treatment, oxidative stress was evaluated by detection of circulating levels of soluble NOX2-derived peptide (sNOX2-dp), a marker of NADPH oxidase activation, and by analyzing platelet ROS formation. Platelet activation was studied by dosing sCD40L. RESULTS: We observed an increase of soluble sNOX2-dp, sCD40L and ROS production in the placebo group compared with the baseline after the surgical intervention. Conversely, in the l-carnitine-treated group, sNOX2-dp, sCD40L and ROS production did not significantly differ from the baseline. A linear correlation analysis showed that Δ of ROS correlated with Δ of sNOX2 (R(s) =0.817; P<0.001) and Δ of sCD40L (R(s) =0.780; P<0.001). Multiple linear regression analysis showed that the only independent predictive variable associated with Δ of ROS was Δ of serum NOX2 levels (SE=0.05; standardized coefficient ß=1.075; P<0.001). CONCLUSION: Our findings suggest that l-carnitine could be helpful in modulating oxidative stress and platelet activation during major abdominal surgery-dependent oxidative damage.

Nutritional Considerations in Frail Older Patients with COVID-19.

The COVID-19 pandemic is posing an unprecedented challenge to healthcare systems worldwide. Older adults, which frequently present multiple chronic comorbidities, are more susceptible to COVID-19 and experience more likely negative outcomes, in terms of disease severity and mortality. However, chronological age per se may not entirely explain the dramatic scenario described among the frailest and oldest persons. Comorbidities and functional status may indeed play a relevant role. Patients at high risk of adverse clinical outcomes in COVID-19 infection are the same at risk of malnutrition, namely older adults and multimorbid individuals. In fact, COVID-19 can negatively impact on nutritional status, both in patients admitted to the hospital with the most severe manifestations of the infection, as well as in those who experience milder/asymptomatic forms of the disease. Despite being quite difficult in these emergency circumstances, nutritional status needs to be assessed in all COVID-19 patients upon admission and during hospital stay. Early nutritional support should be guaranteed in order to improve several malnutrition-related adverse outcomes. The evaluation of the nutritional status is today even more crucial than in normal times given the delicate status of older patients with COVID-19.

Pain Management in Nursing Home Residents: Results from the INCUR Study.

OBJECTIVES: Pain is very common among older persons living in nursing home, affecting 45% to 80% of residents, interfering with daily activities and quality of life. Aims of the study are: 1) to measure the analgesics non-prescription in nursing home residents who present pain symptoms; 2) to identify the main determinants of analgesics non-prescription. DESIGN: Retrospective cross-sectional analysis. SETTING: Data from an observational study ('Incidence of pNeumonia and related ConseqUences in nursing home Residents' [INCUR] study). PARTICIPANTS: 800 older persons living in 13 French nursing homes. Measurments: Pain symptoms were definied by one of the following criteria: i) Presence of pain affecting the individual's function in the Activities of Daily Living; ii) Presence of daily pain, and/or; iii) Severe pain measured with a visual analogue scale. RESULTS: Among the patients originally included in the study, 288 (36%) reported pain symptomatology (mean age 86.9 [SD 7.2] years, 220 (76%) participants women). Amongst these, 138 (47.9%) were treated with non-opioid analgesic drugs, 52 (18.1%) with opioids, and 98 (34%) did not receive any analgesic prescription. An adjusted logistic regression analysis found that the strongest determinant of analgesics non-prescription was the number of concomitantly prescribed drugs (p<0.001). Age, education, and frailty were not associated with prescription of analgesic drugs. CONCLUSIONS: Pain undertreatment is very common among older persons living in nursing homes. The number of prescribed medications represents the most relevant risk factor for the analgesics non-prescription. Our findings document the importance of reviewing prescriptions in nursing home residents.

Plasma adrenomedullin and endothelin-1 levels are reduced and Raynaud's phenomenon improved by daily tadalafil administration in male patients with systemic sclerosis.

The aim of our study is to evaluate in Systemic Sclerosis (SSc) male patients the tadalafil effects on Raynaud's phenomenon and on AM and ET-1 plasma levels. In an open-label study 20 consecutive male patients with SSc were enrolled and received 10 mg of tadalafil daily for 12 weeks. The primary endpoint was the subjective reduction of frequency and duration of Raynaud's attacks measured with a 10-point Raynaud's Condition Score; the secondary aim was to modify Adrenomedullin (AM) and Endothelin-1 (ET-1) plasma levels. After the treatment Raynaud's phenomenon was improved by once-daily tadalafil (decrease of mean number of Raynaud's attacks and of Raynaud's Condition Score) and plasma AM and ET-1 levels decreased. The results of our study lead us to postulate the beneficial effect of adding long term inhibition of Phosphodiesterase type 5 to Systemic Sclerosis' therapy.

Comparison of thermal infrared and laser doppler imaging in the assessment of cutaneous tissue perfusion in scleroderma patients and healthy controls.

In this study we propose a non-invasive method to calculate blood flow by means of thermal infrared imaging and bio-heat transfer modeling. The method is able to provide high time-resolution series of cutaneous blood flow images with the same spatial resolution of the thermal images. The method was tested against a standard laser Doppler imaging system, which to date is considered the gold standard for non-invasive assessment of cutaneous blood flow, on both healthy subjects and patients suffering from systemic sclerosis (SSc; a pathological condition with microvessel endothelium injury). Twenty healthy subjects and twenty SSc patients simultaneously underwent laser Doppler and thermal imaging of the dorsum of the hand. A linear correlation between perfusion values obtained with the two methods was found for the healthy control group (R = 0.85, Pearson Product Moment Correlation). A significant correlation was not observed for the SSc patient group. The results of this study suggest that combined laser Doppler, thermal imaging and bio-heat transfer modeling could effectively discriminate between healthy vs. impaired conditions of the cutaneous tissue thermal properties and cutaneous vasculature. Such method, in addition to providing a potential effective imaging-based tool for a variety of biomedical and clinical applications ranging from diagnostics to treatment follow-up, may help the understanding of the morphological and functional impairment secondary to the disease. The thermal imaging-based method provided faster and better time-resolved imaging of cutaneous perfusion than standard laser Doppler techniques as the thermal cameras can provide up to 100 complete 524 x 524 pixel images per second, thus allowing real time monitoring of tissue perfusion rates.

X-ray absorption and molecular dynamics study of cation binding sites in the purple membrane.

The present work describes the results of a study aimed at identifying candidate cation binding sites on the extracellular region of bacteriorhodopsin, including a site near the retinal pocket. The approach used is a combined effort involving computational chemistry methods (computation of cation affinity maps and molecular dynamics) together with the Extended X-Ray Absorption Fine Structure (EXAFS) technique to obtain relevant information about the local structure of the protein in the neighborhood of Mn(2+) ions in different affinity binding sites. The results permit the identification of a high-affinity binding site where the ion is coordinated simultaneously to Asp212(-) and Asp85(-). Comparison of EXAFS data of the wild type protein with the quadruple mutant E9Q/E74Q/E194Q/E204Q at pH 7.0 and 10.0 demonstrate that extracellular glutamic acid residues are involved in cation binding.

Penile cutaneous temperature in systemic sclerosis: a thermal imaging study.

Systemic Sclerosis is a connective tissue disorder featuring vascular alterations and an immunological activation leading to a progressive and widespread fibrosis of several organs such as the skin, lung, gastrointestinal tract, heart and kidney. Moreover men with systemic sclerosis (SSc) present an increased risk of developing erectile dysfunction (ED). Recently, we evaluated the extent of penile vascular damage in sclerodermic patients using Duplex ultrasonography. The aim of this paper is to investigate whether penile thermal differences exist between sclerodermic patients and healthy controls. For this reason 10 men with SSc receiving current treatment for their disease, and 10 healthy controls were enrolled; penile thermal properties were assessed through non-contact thermal imaging (functional Infra Red Imaging fIRI); erectile function was evaluated using the sexual health inventory for men (SHIM) questionnaire. The SHIM results confirmed the presence of ED in sclerodermic patients. Baseline penile temperature in patients (32.1 +/- 1.4 degrees C) was lower than in controls (34.1 +/- 0.9 degrees C). Recovery from cooling test was seen to be faster in healthy controls than in patients, both in terms of recovery amplitude (patients 3.75 +/- 2.09 degrees C, controls 9.80 +/- 2.77 degrees C) and amplitude to time constant ratio (patients 1.21 +/- 0.64 degrees C/min, controls 1.96 +/- 0.48 degrees C/min). These results show that penile thermal abnormalities occur in almost all sclerodermic patients. Non-contact thermal imaging not only identifies thermal alterations but also clearly distinguishes between SSc patients and healthy controls and therefore could represent a valuable instrument in identifying early ED in SSc patients.

Management and outcomes of hepatic cirrhosis: Findings from the RING study.

BACKGROUND/AIM: Hepatic cirrhosis is a frequent reason for ordinary hospital admission (OA). The RING study collected hospital discharge files (HDF) from Italian hospital gastroenterology units (IGU). This caselist provides a broad picture of the patients admitted for this pathology. MATERIAL/METHODS: More than 50,000 HDF for OA were collected between 2001 and 2004 from 26 IGU. RESULTS: Eight thousand four hundred and eighty-seven HDF (16%) had a diagnosis of hepatic cirrhosis; Child-Pugh classes were 20.2% A, 34.8% B and 45.0% C. Patients' mean age was 63.7+/-12.1 years and 62.5% were male. A 61.1% of the cirrhosis cases had ascites, 29.9% portal-systemic encephalopathy, 29.2% hepatocellular carcinoma (HCC), 10% bleeding varices, 3.0% hepatorenal syndrome (HRS). Mortality for OA for cirrhosis was 5.7% versus 2.6% for other diagnoses. The proportion varied with the severity of the cirrhosis: 0% for Child A, 1.1% B, 10.5% C. Mortality was significantly associated with: Child-Pugh at admission (odds ratio: OR 9.2), HRS (OR 11.7), bleeding varices (OR 2.2), HCC (OR 1.8). CONCLUSIONS: Hepatic cirrhosis was found in 16% of the OA to IGU and mortality was double the rate for all the other pathologies in the same wards. Child-Pugh is a useful prognostic tool, higher classes implying a greater risk of death. HRS and bleeding varices were the complications with most influence on in-hospital mortality.

Atypical disseminated leishmaniasis resembling post-kala-azar dermal leishmaniasis in an HIV-infected patient.

Post-kala-azar dermal leishmaniasis (PKDL) is very uncommon among HIV-positive patients, and very few cases have so far been documented. A case of atypical disseminated leishmaniasis resembling PKDL in an HIV-positive patient successfully treated with N-methylglucamine antimoniate is reported. The polymerase chain reaction performed on the skin lesions was positive for Leishmania infantum.

The combined effect of adiposity, fat distribution and age on cardiovascular risk factors and motor disability in a cohort of obese women (aged 18-83).

Obesity is associated with a number of serious diseases and with a degree of motor disability, but the extent of the risk and functional derangement within the obese population is not yet completely defined. The study aims to evaluate the combined effect of degree of adiposity, body fat distribution and age on selected cardiovascular risk factors and functional motor disability in a cohort of obese women. A multivariate analysis of variance (MANOVA) is employed to show the combined impact of body mass index (BMI), waist-to-hip ratio (WHR) and age on systolic and diastolic blood pressure (SBP and DBP), total and HDL cholesterol (T-CH and HDL-CH), coronary heart disease (CHD) risk, leg power output (W, assessed with a Margaria test for stair climbing) and subjective general fatigue in a cohort of 463 obese women (BMI range 30.2-66.7 kg/m2; age range 18-83 yr). High WHR and older age, but not BMI, are to a variable degree related to unfavorable values of parameters which contribute to the cardiovascular risk. WHR in the high range is associated with significantly higher values of SBP (p<0.001), CHD risk scores (p<0.001) as well as lower levels of HDL-CH (p=0.01), while older age is significantly associated with higher SBP (p<0.001), T-CH (p<0.001) and CHD risk scores (p<0.001). A significant interaction between age and WHR was detected in the effect on DBP (p=0.01), the negative role of high WHR values being apparent in older women (age > or = 51 yr) but not in younger ones (age < 51 yr). Although not significantly related to CHD risk scores, BMI interacted significantly with WHR in determining high risk score values (p=0.01), the negative effect of a high WHR being apparent in women with a high degree of obesity (BMI > or = 40 kg/m2) but not in those with a low one (BMI < 40 kg/m2). In contrast, WHR did not significantly affect W, which appeared to be mainly dependent on age (p<0.001) and BMI (p<0.001), when considered in terms of unit body mass (BM). Subjective global fatigue, however, was unaffected by any of the factors considered. In the present cohort of obese women, older age and excessive abdominal fat distribution (as assessed by WHR) appear to be significant factors in relation to increased cardiovascular disease risk, irrespective of BMI, while older age and higher levels of overall adiposity are associated with functional motor derangement irrespective of body fat distribution. This suggests that obesity increases metabolic risk and induces motor dysfunction by means of different biological mechanisms and with a different impact within the obese female population.

Significant changes of peripheral perfusion and plasma adrenomedullin levels in N-acetylcysteine long term treatment of patients with sclerodermic Raynauds phenomenon.

The unclear pathogenesis of scleroderma vascular lesions makes treatment of Raynaud's phenomenon (RP) in Systemic Sclerosis (SSc) patients very difficult and a new effective treatment is requested. Recently, a powerful antioxidant agent, the N-acetylcysteine (NAC) has been shown to decrease the frequency and severity of RP in SSc patients. Subsequently, using functional infrared imaging, we showed that a single 1-hour NAC infusion in these patients caused a significant increase of skin temperature. The aim of this study was to demonstrate the efficacy of long term therapy with NAC in an open clinical trial evaluating clinical, instrumental and laboratory parameters. Patients started the treatment receiving for two years, from October to May, intravenous NAC infusions of 15 mg/kg per hour each, for 5 consecutive hours, every two weeks. Before and after each infusion, patients underwent both Laser Doppler perfusion Imaging (LDPI) for the evaluation of the digital perfusion and a blood test to ascertain the plasma adrenomedullin (AM) levels. The NAC infusion increased global hands perfusion and induced a significant decreasing of plasma AM concentrations. Side effects were negligible, easy to control and reversible. Reduction of frequency and severity of RP attacks was recorded. In conclusion, NAC seems to act as an effective vasodilatator in the treatment of RP secondary to SSc and, in addition, it induced significant changes in plasma levels of AM, a potent vasodilator endothelial-derived peptide.

In vitro depressant effects of U-54494A, an anticonvulsant related to kappa opioids, in the hippocampus.

The effects of cis-3,4 dichloro-N-2-(1-pyrrolidinyl)cyclo-hexyl-benzamide (U-54494A), an anticonvulsant related to kappa opioids, were studied in vitro on the extracellular electrical activity of the CA1 region of slices of hippocampus in the rat. The effects of U-54494A were compared to those of the kappa opioid agonist trans-3,4 dichloro-N-2-(1-pyrrolidinyl)cyclo-hexyl benzeneacetamide methane sulphonate (U-50488H). Both U-54494A and U-50488H, in concentrations of 50 and 100 microM, respectively, reduced the magnitude of the orthodromically evoked CA1 population spikes after electrical stimulation of the stratum radiatum (100-200 microA, 70 microseconds, 0.1 Hz). Naltrexone (25 microM), or the selective kappa opiate receptor antagonist, 1-cyclopenthyl-5-(1,2,3,4,5,6-hexahydroxy-3,6,11-trimethyl-2 -6-methano-3- benzazocin)-3-pentatone methane sulphonate (WIN 44441-3) (25 microM), prevented the depressant activity of U-54494A (200 microM) on the CA1 population spikes. High calcium (+3mM) solutions prevented the depressant activity of increasing concentrations of both U-54494A and U-50488H on the amplitude of CA1 population spikes. Up to 200 microM, both drugs were ineffective in depressing the epileptiform bursting in CA1, due to 1 mM penicillin or to perfusion of the slice in absence of magnesium ions. The results demonstrate: (1) the inability of U-54494A to show antagonistic activity in two in vitro models of interictal epilepsy; (2) a depressant effect of U-54494A on basal synaptic transmission in the CA1 region of the hippocampus, which may be related to an influence on transneuronal calcium currents and which may be involved in the reported antagonism of ictal epileptic seizures by drugs.

Investigation of Dienophile-TiCl(4) Complexation by Means of X-ray Absorption and (13)C-NMR Spectroscopies.

Extended X-ray absorption fine structure (EXAFS) and X-ray absorption near edge structure (XANES) techniques, in combination with (13)C-NMR spectroscopy, have been used to study the complexation of methyl acrylate (1), N-acryloylbenzylamine (2), O-acryloyl-(R)-pantolactone (3), methyl N-acryloyl-(S)-prolinate (4), and methyl N-acryloyl-(S)-phenylalaninate (5) with excess TiCl(4) in solution. The results obtained show that TiCl(4) has a great tendency to coordinate with two ester ligands, but this tendency is not so marked with amides, which is related to the greater basicity of the latter. Complexation increases the Ti-Cl bond distance, in comparison with TiCl(4), which is clearly shown by the EXAFS spectra. Chelate complexes are formed with bidentate ligands, but comparison between the EXAFS spectra, obtained with different TiCl(4)/dienophile ratios, shows that chelation is more difficult with methyl N-acryloyl-(S)-phenylalaninate (5).

Immune effects of nickel.

Data on nickel immunomodulation are contradictory. The most consistent immune effects are suppression of immune responses. It has been shown that T-lymphocytes and NK cells are more susceptible to nickel toxicity than are B lymphocytes or macrophages. Data reported about cytokine production in human and nickel reactive T-cell clones are also conflicting. Some authors studied showed a higher synthesis of IL4, IL5 and IL13 but not of IFN gamma and TNFalpha in Ni allergic subjects. We found that the addiction on NiSo4 to the PBMC cultures of non sensitised subjects induces a reduction of release of IL5, IFN gamma and TNFalpha. Our studies demonstrate a clear difference in the NK cell activity between nickel-tolerant and intolerant individuals. In particular NK cell activity in reduced in sensitised patients respect to the normal subjects and the addition of Ni has immunotoxic potential. Researches are in progress in an Attempt to correlate the present data with other immune parameters and to measure the effects of a Ni Free diet on the immune system of subjects with Ni intolerance. The comprehension of the mechanisms inducing these changes requires further studies in the uptake and intracellular distribution and binding of the metal.