A longitudinal evaluation of changes in disability and quality of life in a sample of women with migraine

Migraine’s high prevalence, which rises up to 25% among women in the productive age, determines a strong reduction in health-related quality of life (HRQoL) and increased disability. Aim of this study is to longitudinally describe disability and HRQoL in a sample of adult women with migraine attending to a specialty centre. HRQoL was measured with the SF-36 and disability with the WHO-DAS II. One-sample t test was used to assess deterioration in disability and HRQoL scales compared to normative scores; effect size was calculated to describe magnitude of change after 3 months. Majority of scales were significantly deteriorated, and changes between baseline and follow-up were negligible to small for most of SF-36 scales, and small to moderate for WHO-DAS II scales. In conclusion, women with migraine showed pervasive deterioration in disability and HRQoL. Wider improvements were observed at follow-up for activities in which relational skills are relevant, while those with a physical component, or that are predominantly performed autonomously, remained almost unchanged.     

Predictors of Bone Responsiveness to Growth Hormone (GH) Replacement in Adult GH-Deficient Patients

Growth hormone (GH) replacement in adulthood results in variable bone responses as a function of the gonadic hormonal milieu. We performed a retrospective analysis of a large cohort of adult males and females with confirmed GH deficiency (GHD) prior to treatment and during 3 years of replacement therapy. Potential confounders and effect modifiers were taken into account. Sixty-four adult patients with GHD (20 females and 44 males; mean age 34 years, range 18–64) were included in the analysis. GH replacement induced a different effect on bone in males compared to females. Bone mineral content increased in males and decreased in females at the lumbar spine, total femur, and femoral neck; bone mineral density showed a similar trend at the lumbar spine and femoral neck. There was no significant gender difference in bone area at any measured bone site. In both sexes we observed a similar trend for serum markers of bone remodeling. Sex predicted bone outcome on multivariate analysis, as did age, onset of GHD (childhood/adulthood), pretreatment bone mass, baseline body mass index (BMI), and BMI change during GH replacement. Serum IGF-I levels during treatment did not show any relationship with bone outcome at any measured site. This study confirms that bone responsiveness to GH replacement in adult GHD varies as a function of sex even after controlling for potential confounders and highlights the importance of other cofactors that may affect the interaction between GH replacement therapy and bone remodeling.     

GLUTs and mammalian sperm metabolism

Mammalian cells use glucides as a substrate that can be catabolized through glycolitic pathways or oxidative phosphorylation, used as a source of reducing potential, or used for anabolic aims. An important role in supplying cells with energy is played by different membrane proteins that can actively (sodium-dependent glucose transporters) or passively (glucose transporters; GLUT) transport hexoses through the lipidic bilayer. In particular, GLUTs are a family of 13 proteins that facilitate the transport of sugars and have a peculiar distribution in different tissues as well as a particular affinity for substrates. These proteins are also present in mature sperm cells, which, in fact, need carriers for uptake energetic sources that are important for maintaining cell basic activity as well as specific functions, such as motility and fertilization ability. Likewise, several GLUTs have been studied in various mammalian species (man, bull, rat, mouse, boar, dog, stallion, and donkey) to point out both their actual presence or absence and their localization on plasma membrane. The aim of this work is to give an overall picture of the studies available on GLUTs in mammalian spermatozoa at this moment, pointing out the species peculiarity, the possible role of these proteins, and the potential future research on this item.     

An evaluation of the relationships between catheter design and tissue mechanics in achieving high-flow convection-enhanced delivery

Convection-enhanced delivery (CED) is a rational technique for the direct intracranial administration of a range of therapeutic agents. CED critically depends on the use of a catheter with a narrow outer diameter and low infusion rate. Failure to adhere to these requirements can lead to reflux of infusate along the catheter-brain interface and damage at the catheter-tip. In this study we have tested the hypothesis that the relationship between infusion parameters and infusate distribution, including reflux, is critically dependent on the occurrence of tissue damage. The relationship between catheter outer diameter and the extent of blood-brain barrier disruption and subsequent tissue oedema was evaluated following catheter insertion into the striatum of rats. Three patterns of infusate distribution were observed: (1) Reflux restricted to the traumatised tissue around the catheter site. (2) Distribution in the white matter beyond the area of tissue trauma. (3) Widespread distribution in the striatum, which occurred only with catheters of an outer diameter of 0.35 mm or less. Extensive tissue damage occurred with a 0.2mm outer diameter catheter. This damage was completely prevented by rounding the catheter-tip. Infusions into pig brain demonstrated that high-flow CED could be performed in a large brain in both grey and white matter using a 0.2mm outer diameter catheter, with minimal reflux or MRI-evidence of tissue damage. This study demonstrates that by minimising tissue damage from catheter design and insertion, high flow-rate CED can be utilised to distribute therapeutic agents over large volumes of brain within clinically practical timescales.     

The impact of schizophrenia on frontal perfusion parameters: a DSC-MRI study

We performed a dynamic susceptibility contrast magnetic resonance imaging (DSC-MRI) analysis to study the role of the demographic/clinical information on perfusion parameters between patients with schizophrenia and normal control subjects. 39 schizophrenia patients and 27 normal controls were studied with a Siemens 1.5T magnet. PWI images were obtained following intravenous injection of paramagnetic contrast agent (gadolinium-DTPA). For each perfusion parameter, i.e. relative cerebral blood flow (rCBF), relative cerebral blood volume (rCBV), mean transit time (MTT) and time-to-peak (TTP), the best predictor model was computed in left and right frontal cortex following a stepwise strategy. First of all, a linear model, including all the sociodemographic information and clinical variables as predictors was computed. At each step, the least significant predictor was excluded and a new linear model was evaluated until all predictors were excluded. Then, the best predictor model was selected based on the F statistic value and on the p value. The models for the rCBF and the rCBV both in the left and right frontal cortex were estimated independently from each other, and the best models contained the same predictors, i.e. clinical state, age, and length of illness. No significant models were obtained for the MTT and the TTP. This study showed a decrease in rCBF and rCBV frontal cortex values in subject affected by schizophrenia. Future DSC-MRI studies should further investigate the role of cerebral perfusion for the pathophysiology of the disease by recruiting first-episode patients and by considering cerebellar, parietal and temporal regions.     

Investigation of shared genetic effects for psychotic and obsessive symptoms in young adult twins

Genetic and environmental architecture of psychotic and obsessive symptoms are not completely elucidated. This study estimated for these symptoms (i) the genetic and environmental components, (ii) the within-individual association, and (iii) the extent to which this association originates from common genetic and environmental factors. Young adult twins (N = 701) from the population-based Italian Twin Register were assessed for psychotic and obsessive-compulsive symptoms by using the Symptom Check List (SCL-90). Multivariate Cholesky models were fitted by the Mx statistical program. No previous study used this design to examine the same dimensions. The best-fitting model included additive genetic and nonshared environmental components, each accounting for about half of total variance in the symptoms. Genetic influences on the different symptoms overlapped considerably (r_g = 0.81 to 0.99). Phenotypic correlations of psychotic symptoms and of psychotic with obsessive symptoms were high (r = 0.61 to 0.76), with 53% to 69% explained by shared genetic effects. This study shows substantial genetic influence on psychotic and obsessive symptoms, and indicates that their co-occurrence may be due to genetic factors to a greater extent than to environmental effects. These results encourage the search for genetic and environmental factors underlying the covariance between different psychotic traits as well as between psychotic and obsessive traits.     

Cerebellar and lobar blood flow in schizophrenia: a perfusion weighted imaging study

Accumulating evidence indicates that cannabis use may be a risk factor for schizophrenia (SZ), and chronic cannabis users score higher than non-users on measures of schizotypal personality traits. The purpose of the present study was to investigate the relations between normal personality, schizotypy, and cannabis use. Sixty-two chronic cannabis users and 45 cannabis-naïve controls completed a measure of normal personality, the NEO-Five Factor Inventory (NEO-FFI), and two measures of schizotypy, the schizotypal personality questionnaire (SPQ) and perceptual aberration scale (PAS). Substance use was assessed using the SCID I alcohol/drug module and a locally developed drug use questionnaire. On the NEO-FFI, users scored higher than controls on openness, but lower on agreeableness and conscientiousness, and endorsed greater schizotypy on the SPQ and PAS. Higher neuroticism predicted greater schizotypy in both groups, and, higher Extraversion predicted lower negative-syndrome schizotypy among users. Finally, duration of cannabis use was positively correlated with scores on the SPQ and PAS among users, suggesting a relation between overall cannabis use chronicity and schizotypy. These data show that cannabis users differ from non-users on dimensions of normal personality and schizotypy, and provide further evidence that cannabis use is associated with increased levels of psychosis-related personality traits.     

Thermal, spectroscopic, and ab initio structural characterization of carprofen polymorphs

Commercial and recrystallized polycrystalline samples of carprofen, a nonsteroidal anti-inflammatory drug, were studied by thermal, spectroscopic, and structural techniques. Our investigations demonstrated that recrystallized sample, stable at room temperature (RT), is a single polymorphic form of carprofen (polymorph I) that undergoes an isostructural polymorphic transformation by heating (polymorph II). Polymorph II remains then metastable at ambient conditions. Commercial sample is instead a mixture of polymorphs I and II. The thermodynamic relationships between the two polymorphs were determined through the construction of an energy/temperature diagram. The ab initio structural determination performed on synchrotron X-Ray powder diffraction patterns recorded at RT on both polymorphs allowed us to elucidate, for the first time, their crystal structure. Both crystallize in the monoclinic space group type P2(1) /c, and the unit cell similarity index and the volumetric isostructurality index indicate that the temperature-induced polymorphic transformation I → II is isostructural. Polymorphs I and II are conformational polymorphs, sharing a very similar hydrogen bond network, but with different conformation of the propanoic skeleton, which produces two different packing. The small conformational change agrees with the low value of transition enthalpy obtained by differential scanning calorimetry measurements and the small internal energy computed with density functional methods.     

Reduced antiarrhythmic efficacy of verapamil in isolated rat hearts in the presence of elevated extracellular calcium

An isolated heart method that has been proposed to aid in ascertaining the involvement of L-type calcium channel blockade in the mechanism of action of novel antiarrhythmic drugs involves increasing the calcium concentration in the perfusion buffer. The purpose of this study was to determine the validity of this method using an established L-type calcium channel blocker, verapamil. Isolated rat hearts were perfused with normal calcium (1.4 mM) Krebs solution containing drug vehicle only, a normal calcium solution containing verapamil (300 nM), or a high calcium (2.8 mM) solution containing verapamil. The occurrence of ventricular fibrillation during a subsequent period of regional myocardial ischemia was monitored. The incidence of ventricular fibrillation was significantly reduced from 80% in controls to 20% by perfusion with verapamil in normal calcium Krebs solution (P < 0.05). Perfusion with the high calcium solution increased the incidence of ventricular fibrillation in the presence of verapamil to 40% (P > 0.05 versus controls). We conclude that the antiarrhythmic effect of verapamil in isolated hearts can be attenuated by increasing the calcium content of the perfusion solution, but a twofold increase in the calcium concentration failed to fully restore susceptibility to ventricular fibrillation to that observed in verapamil-free controls.