The Expanded Hansen Approach to Solubility Parameters. Paracetamol and Citric Acid in Individual Solvents

In this study two solubility-parameter models have been compared using as dependent variables the logarithm of the mole fraction solubility, lnX₂^e, and ln(α)/U (originally used in the extended Hansen method), where α is the activity coefficient and U is a function of the molar volume of the solute and the volume fraction of the solvent. The results show for the first time the proton-donor and -acceptor hydrogen-bonding capacities of paracetamol, as measured by the acidic and basic partial-solubility parameters. The influence of solvents on the differential scanning calorimetry (DSC) pattern of the solid phases was also studied in relation to the solubility models tested. Citric acid was chosen as a test substance because of its high acidity and its proton donor capacity to form hydrogen bonds with basic solvents. The partial acidic and basic solubility parameters obtained from multiple regression were consistent with this property, validating the model chosen. The results show that the more direct lnX₂^e variable was more suitable for fitting both models, and the four-parameter model seemed better for describing the interactions between solvent and solute.     

Atrial Evoked Response Integral for Automatic Capture Verification in Atrial Pacing

BORIANI, G., et al.: Atrial Evoked Response Integral for Automatic Capture Verification in Atrial Pacing . Beat-by-beat Autocapture is currently limited to operation in the ventricle with bipolar leads. The authors investigated the integral of the negative-going portion of the atrial evoked response integral (AERI) as a potential resource for verification of atrial capture. Intracardiac electrogram signals were collected from 59 patients (ages 67.8 ± 15.1 years) with bipolar, low polarization atrial leads. The signals were collected over a mean period of 6.1 months (minimum 4 days) after lead implantation. St. Jude Medical Affinity pulse generators were used to perform automatic capture threshold tests while the electrogram signals were recorded by a Model 3510 programming device. These signals were transferred to a personal computer in digital form for later analysis. The AERI was calculated at each programmable pacing voltage until capture was lost. The difference between the polarization integral at loss of capture and evoked response integral with successful capture was sufficient to justify enabling the atrial Autocapture feature in 53 of 59 patients in whom bipolar pacing and unipolar sensing was performed. The authors developed a calibration routine to identify automatically those patients in whom atrial Autocapture could be programmed On, based on the polarization integral at loss of capture, the estimated maximum polarization integral, and the AERI. Preliminary analysis indicated that the AERI is a practical resource for beat-by-beat atrial capture detection when used with low polarization leads. (PACE 2003; 26[Pt. II]:248–252)     

Systemic and Secretory Humoral Immunity in the Normal Human Vaginal Tract

The molecular status of Abs in the vaginal fluid is reconsidered as a basis for immunization strategies for women's vaccination against HIV. Analysis of separated immunogiobulins (Igs) shows a large proportion of uncleaved IgG, whereas the low amount of IgA includes SIgA, monomers and fragments. SIgM is at a very low level, while free SC molecules are abundant. In addition to the already documented local synthesis, vaginal IgG contains serum-derived tetanus antitoxins. The IgG could reach the lumen by diffusion, and/or be transported by an Fc receptor-associated mechanism as suggested by the subclass imbalance in favour of the IgGl isotype. Vaginal SIgA contains very low levels of antibodies to the cell-wall carbohydrates from a dental caries-associated streptococcus confirming the participation of the secretory immune system. In addition, the low percentage of IgA2 suggests that a proportion of vaginal SIgA can also derive from actively transported serum polymers. In agreement with our previous studies showing induction of vaginal tetanus antitoxins by intramuscular immunization, these results are in favour of classical parenteral vaccinations to induce protection of the human vagina.     

Assessment and Validation of US EPA's OncoLogic® Expert System and Analysis of Its Modulating Factors for Structural Alerts

OncoLogic® is a software program able to screen chemical compounds for toxicological effects. The software predicts the potential carcinogenicity of chemicals by applying rules of structure activity relationship (SAR) analysis. To validate the predictivity of OncoLogic® (Version 7.0), 123 compounds tested with the long-term carcinogenicity bioassay on rodents were extracted from the ISSCAN database and were analyzed. The concordance between the OncoLogic® SAR analysis and the bioassay results was high. To better understand the strength of the SAR science in OncoLogic®, we investigated the influence of a select group of modulating factors on the predictions by the structural alerts.     

Presence and Duration of Atrial Fibrillation Detected by Continuous Monitoring: Crucial Implications for the Risk of Thromboembolic Events

AF and the Risk of Thromboembolic Events. Introduction: Asymptomatic atrial fibrillation (AF) can expose patients to the risk of stroke. The primary objective of this study was to assess the incidence of thromboembolic events in relationship with CHADS₂ (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke, or transient ischemic attack) score and AF presence/duration. The secondary objective was to compare intermittent versus continuous monitoring strategies. Methods and Results: Data from patients with an implanted pacemaker and a history of AF were analyzed. Thromboembolic risk was quantified through CHADS₂ score. Three AF groups were considered: patients with <5‐minutes AF on 1 day (AF‐free); patients with >5‐minutes AF on 1 day but <24 hours (AF‐5 minutes); patients with AF episodes >24 hours (AF‐24 hours). Monitoring strategies involving 24‐hour Holter, 1‐week Holter, and 30‐day Holter were simulated. Data from 568 patients continuously monitored for 1 year were analyzed: 171 (30%) had CHADS₂ score = 0; 269 (47%) had CHADS₂ score = 1; 111 (20%) had CHADS₂ score = 2; and 17 (3%) had CHADS₂ score ≥ 3. During follow‐up, 14 patients (2.5%) had an ischemic thromboembolic event. AF‐24 hours patients numbered 223 (39.2%); AF‐5 minutes, 179 (31.5%); and AF‐free, 29.2%. By combining AF presence/duration with CHADS₂ score, two subpopulations with markedly different risks of events (0.8% vs 5%, P = 0.035) were identified, the former corresponding to AF‐free with CHADS₂≤2, or AF‐5 minutes with CHADS₂≤1, or AF‐24 hours with CHADS₂= 0. The mean sensitivity in detecting an AF episode lasting >5 minutes was 44.4%, 50.4%, and 65.1% for 24‐hour Holter, 1‐week Holter, and 1‐month Holter monitoring, respectively. Conclusion: In patients with recurrent AF episodes, risk stratification for thromboembolic events can be improved by combining CHADS₂ score with AF presence/duration. (J Cardiovasc Electrophysiol, Vol. 20, pp. 241‐248, March 2009)     

Left Atrial Dysfunction in Patients with Patent Foramen Ovale and Atrial Septal Aneurysm Scheduled for Transcathter Closure May Play a Role in Aura Genesis

Background: It has been suggested that a left atrial (LA) dysfunction induced by large shunt and large atrial septal aneurysm (ASA) may act as a concurrent mechanism of arterial embolism in patients with patent foramen ovale (PFO) and prior stroke. We aimed to evaluate the potential contribution of this mechanism as trigger of migraine in patients with PFO. Methods: From January 2007 to September 2009, we prospectively enrolled subjects with migraine who underwent percutaneous PFO closure. Echocardiographic parameter of LA dysfunction was evaluated: pre‐ and postoperative values were compared to values of different sex and heart rate matched populations: 30 healthy patients, 21 migraine patients without PFO (MwoPFO), and a group of 25 PFO patients without migraine (PFOwoM). The Migraine Disability Assessment Score (MIDAS) was used to assess the incidence and severity of migraine. Results: Forty‐five patients (38 females, mean age 38 ± 6.7 years, mean MIDAS 35.8 ± 4.7, and 28 patients with migraine with aura) fulfilled the inclusion criteria. After successful percutaneous closure (mean follow‐up of 18.2 ± 4.8 months), PFO closure remained complete in 95%; 35 of 45 patients reported resolution or amelioration of migraine (mean MIDAS score 12.3 ± 8.8, P < 0.03). All patients with aura reported aura resolution. Preclosure values demonstrated significantly greater LA dysfunction, when compared with healthy and MwoPFO groups. Among patients in the study group, only patients with migraine with aura showed LA dysfunction comparable to PFOwoM patients. Conclusion: This study suggests that LA dysfunction probably does not contribute to migraine itself but may play a role in the genesis of aura symptoms. (J Interven Cardiol 2010;23:370–376)     

Inhibition of Feline Immunodeficiency Virus Infectionin Vitroby Envelope Glycoprotein Synthetic Peptides

Sixty-six 20- to 23-amino-acid synthetic peptides, partially overlapping by 10–12 amino acids, spanning the entire sequence of the envelope SU and TM glycoproteins of the Petaluma isolate of FIV, have been used to investigate the Env domains involved in viral infection. Peptides 5 to 7, spanning amino acids²²⁵E–P²⁶⁴located in a conserved region of the SU protein, and peptides 58 to 61, spanning amino acids⁷⁵⁷N–P⁸⁰⁶and encompassing hypervariable region 8 of TM protein, exhibited a remarkable and specific antiviral effect against the homologous and one heterologous isolate, as judged by inhibition of FIV-induced syncytium formation and p25 production in CrFK cells. Peptides 5 and 7, but not peptides 58 and 59, also inhibited viral replication of a fresh FIV isolate on nontransformed lymphoid cells. By flow cytometry, peptides 5, 7, 58, and 59 were shown to bind the surface of FIV permissive cells. The antiviral activity of peptides 5 and 7, however, was time-dependent, as inhibition of FIV replication was seen when the peptides were administered before or within 3 hr after virus inoculation; in contrast, TM peptides 58 and 59 exerted a potent inhibitory effect when added up to 24 hr after virus inoculation. Circular dychroism analysis showed that peptide 5 folds to a helical conformation in the presence of a hydrophobic environment. Although the basis for the antiviral action of the peptides is not understood, our data suggest that the inhibitory peptides may act by interacting with cell-surface molecules involved in viral infection.