Effect of the leaving group and solvent combination on the LFER reaction constants.

Fine effects that influence the variations of the reaction constants s(f) in LFER log k = s(f)(N(f) + E(f)) have been summarized here. Increasing solvent polarity in the series of binary mixtures increases the solvolysis rates for the same factor for all benzhydryl derivatives in which the solvation of the leaving group moiety in the transition state is substantial, i.e., log k vs. E(f) correlation lines are parallel (same s(f)). For the substrates in which the demand for solvation of the leaving groups moiety is reduced, (e.g., carbonates) s(f) parameters decrease as the fraction of the water in a given solvent/water mixture increases (log k vs. E(f) plots converge), due to decreasing solvation of the electrofuge moiety toward bigger electrofugality. The abscissa of the intersection of the converging plots might indicate the critical electrofugality above which the solvolysis rates should not depend of the water fraction. Larger reaction constant s(f) indicate later transition state for structurally related substrates only, while s(f) parameters for structurally different substrates cannot be compared likely due to different intrinsic barriers. Inversion in relative abilities of leaving groups is possible if they have similar reactivities and are characterized with different reaction constants.

Leaving group property of dimethyl sulfide.

The LFER equation log k = s(f)(E(f) + N(f)) was used to derive the nucleofuge specific parameters (N(f) and s(f)) for dimethyl sulfide in the series of aqueous alcohols, using the S(N)1 solvolysis rate constants obtained for X-substituted benzhydryl dimethyl sulfonates 1-5. The slope parameters (s(f)) are practically independent of the solvent used, while N(f) parameters slightly decrease as the polarity of the solvent increases.

Zolpidem (Ambien) in pregnancy: placental passage and outcome.

To examine the extent and clinical sequelae of fetal exposure to zolpidem, a commonly prescribed hypnotic agent. Pregnant women with psychiatric illness participating in a study of psychotropic pharmacokinetics were included. Zolpidem concentrations were analyzed in maternal and umbilical cord plasma collected at delivery. Outcomes were compared between the zolpidem-exposed group and a 1:1 matched comparator group. Forty-five women taking zolpidem during pregnancy were studied. Rates of preterm delivery and low birth weight were 26.7% and 15.6% respectively in the zolpidem-exposed group versus 13.3% and 4.4% in the matched comparator group, but no significant differences were found. The ratio of umbilical cord to maternal plasma zolpidem concentrations in 6 pairs ranged from 0.48 to 2.75. Zolpidem crosses the human placenta and rapidly clears the fetal circulation. Pregnant women with psychiatric illness treated with zolpidem may have less optimal obstetrical outcome, though it is unclear if this was related to the medication.

Lamotrigine in bipolar disorder: efficacy during pregnancy.

OBJECTIVE: Clinical management of bipolar disorder (BPD) patients during pregnancy is a major challenge. The high risk of bipolar depression during pregnancy encourages consideration of lamotrigine (LTG). We therefore compared recurrence risks among pregnant women with BPD treated with LTG to those discontinuing mood stabilizer therapies. METHODS: We compared risks and weeks to new DSM-IV illness-episodes among 26 initially clinically stable pregnant women diagnosed with DSM-IV BPD who continued LTG treatment to those discontinuing all mood stabilizer treatment during pregnancy. RESULTS: The risk of new illness-episodes with LTG was 30% versus 100% after discontinuing mood stabilizers, and survival-computed time-to-25%-recurrence was 28.0 versus 2.0 weeks (chi(2 )=17.3, p < 0.0001; hazard ratio = 12.1; 95% confidence interval = 1.6-91.7). CONCLUSIONS: Discontinuing mood stabilizer treatment presents high risks of illness-recurrence among pregnant women diagnosed with BPD. LTG may afford protective effects in pregnancy, and its reported fetal safety compares favorably to other agents used to manage BPD.

Bismuth nanoparticles-carbon nanotubes modified sensor for sulfasalazine analysis.

Nanocomposite of bismuth nanoparticles and carbon nanotubes in Nafion matrix was used as modifier for glassy carbon electrode in analysis of anti-inflamatory drug sulfasalazine. The nanocomposite surface exhibited exceptional synergy and remarkable enhancement effect to the voltammetric response of drug. The surface morphology and structure characterization of the modified electrodes was characterized by scanning electron microscopy, energy dispersive X-ray spectroscopy and cyclic voltammetry. The sensor exhibited excellent electroanalytical performance for drug determination in comparison with bismuth film electrode. The adsorptive stripping square-wave voltammetric signal showed a good linear correlation to sulfasalazine concentration in a broad range from 5.0×10-8 to 1.0×10-5M with low detection limit of 1.3×10-8M.The method was successfully utilised for drug quantification in human serum samples and good recoveries were obtained without interference from endogenous substances, 5-aminosalycilic acid and sulfapyridine formed after biotransformation of drug and folic acid co-administered as the supplement during sulfasalazine therapy. Additionally, the proposed sensor was successfully applied to analysis of sulfasalazine content in gastro-resistant pharmaceutical dosage forms.

Quantitative Analysis of Phenolic Acids and Antiplatelet Activity of Melissa officinalis Leaf Extracts.

The contents of total phenolic acids and rosmarinic acid were determined and the antiplatelet potential assessed of extracts of lemon balm (Melissa officinalis L., Lamiaceae) leaf samples collected during 2014 and 2015. The quantity of total phenolic acids ranged from 4.8 to 8.5%, while the rosmarinic acid content ranged from 1.78 to 4.35%. Results of statistical analysis showed that the undiluted extracts have antiplatelet activity in the ADP test (final concentration 31.25 mg/L). While there are reports on antiplatelet activity of lemon balm essential oil, to the best of our knowledge, this is the first report on antiplatelet activity of lemon balm leaf extracts.

Electrochemical sensing of mesalazine and its N-acetylated metabolite in biological samples using functionalized carbon nanotubes.

A rapid analytical method without the time-consuming separation step was developed to simultaneously determine mesalazine and its N-acetylated metabolite. A simply designed electrochemical sensor with functionalized carbon nanotubes in a Nafion matrix was constructed for this purpose. The presence of the nanocomposite modifier on the electrode surface significantly affects the voltammetric response of target analytes. The morphology of the modified surface was investigated by scanning electron microscopy. The effect of modifier amount on the sensor performance was investigated in order to obtain the most favorable response of mesalazine since it was found in lower concentration limits in real samples then its metabolite due to the rapid drug elimination and the slightly slower renal metabolite excretion. Under optimal conditions, the anodic peak currents measured by square-wave voltammetry increased linearly after short accumulation of 30s in the range of 5.0×10(-8)-2.5×10(-6)M and 1.0×10(-7)-5.0×10(-6)M for drug and metabolite, respectively. In addition to stable response, the sensor has excellent performance associated with high sensitivity (2.33×10(7) and 8.37×10(6)µAM(-1) for drug and metabolite, respectively). The synergistic effect of the carbon nanotubes and Nafion polymer film yielded detection limit of 1.2×10(-8)M for mesalazine and 2.6×10(-8)M for its metabolite that is comparable to known chromatographic methods. Due to the easy preparation and regeneration, the proposed sensor opens new opportunity for fast, simple and sensitive analysis of drug and its metabolite in human serum samples as well as direct quantification of mesalazine in delayed-release formulations.

Newly onset sinus bradycardia in the context of multiple sclerosis relapse.

Cardiovascular disorders in acute multiple sclerosis (MS) relapse have been infrequently reported. We present a young multiple sclerosis patient with acute onset of cerebellar symptomatology along with sinus bradycardia. Brain magnetic resonance imaging showed one lesion in the left cerebellar hemisphere which showed postcontrast enhancement and one in the midbrain without postcontrast enhancement. No cardiac pathology was found and symptoms gradually improved after a 5-day course of corticosteroid therapy. It is important to bear in mind the possibility of these rare cardiac symptoms in MS patients, because of their timely recognition and appropriate treatment.

Kinetics of the solvolyses of benzhydryl derivatives: basis for the construction of a comprehensive nucleofugality scale.

A series of 21 benzhydrylium ions (diarylmethylium ions) are proposed as reference electrofuges for the development of a general nucleofugality scale, where nucleofugality refers to a combination of leaving group and solvent. A total of 167 solvolysis rate constants of benzhydrylium tosylates, bromides, chlorides, trifluoroacetates, 3,5-dinitrobenzoates, and 4-nitrobenzoates, two-thirds of which have been determined during this work, were subjected to a least-squares fit according to the correlation equation log k(25 degrees C) = sf(Nf + Ef), where sf and Nf are nucleofuge-specific parameters and Ef is an electrofuge-specific parameter. Although nucleofuges and electrofuges characterized in this way cover more than 12 orders of magnitude, a single set of the parameters, namely sf, Nf, and Ef, is sufficient to calculate the solvolysis rate constants at 25 degrees C with an accuracy of +/-16 %. Because sf approximately 1 for all nucleofuges, that is, leaving group/solvent combinations, studied so far, qualitative discussions of nucleofugality can be based on Nf.

How fast do R-X bonds ionize? A semiquantitative approach.

The correlation equation log k(25 degrees C) = sf(Nf + Ef), where sf and Nf are nucleofuge-specific parameters referring to leaving group/solvent combinations and Ef are electrofuge-specific parameters referring to the incipient carbocation R+, are used to predict ionization rate constants of alkyl derivatives R--X. We show how to employ the Ef parameters of reference electrofuges and the sf and Nf parameters of reference nucleofuges reported in the preceding article for determining further sf, Nf, and Ef parameters. Since sf is usually close to 1.0, one comes to the semiquantitative rule that at 25 degrees C, compounds R--X for which Nf + Ef>-2 will solvolyze with half-lives of less than a minute, while the solvolysis half-lives will exceed 1 month if Nf + Ef<-6.5.

[Characteristics of cesarean sections at the University Hospital Mostar]. / Osobitosti carskih rezova u Klinickoj bolnici Mostar.

We performed a retrospective, descriptive study in order to analyze characteristics of the cesarean sections at the University Hospital Mostar in year 2002. We analyzed cesarean sections incidence, general characteristics of the parturients and neonates, major indications for the cesarean section and postoperative course. During year 2002, there were 247 cesarean sections out of total of the 1510 deliveries. Total of 255 neonates were born by this operative procedure and 16 of them were twins. We used the operational, labour, neonate and parturients records in order to collect data. The incidence of cesarean sections in University Hospital Mostar in year 2002 was 16.4%. There were 5.3% elective procedures. Most of the parturients were in age group 25-35. More than half of the parturients gave birth for the first time. The major diagnoses for cesarean section were previous cesarean section, fetal distress, breech presentation, cephalo-pelvine dysproportion and dystocia. Most of the pregnancies terminated by cesarean section (87.3%) were in term. The majority of neonates had weight > or = 2500 g (93.7%) and first minute Apgar score > or = 7 (96.4%). Parturients stayed for a week in the hospital and were given antibiotic prophylaxis postoperatively. Each second parturient suffered from pyrexia of unknown origin postoperatively. Comparing to literature data, we found high incidence of cesarean sections considering total number of deliveries and pregnancy pathology. We think that proper measures of decreasing this incidence should take place in University Hospital Mostar.

Solvolysis of 1,1-dimethyl-4-alkenyl chlorides: evidence for pi-participation.

Tertiary 1,1-dimethyl-4-alkenyl chloride (1) solvolyzes with significantly reduced secondary beta-deuterium kinetic isotope effect (substrate with two trideuteromethyl groups) and has a lower entropy and enthalpy of activation than the referent saturated analogue 4 (k(H)/k(D) = 1.30 +/- 0.03 vs k(H)/k(D) = 1.79 +/- 0.01; Delta Delta H(++) = -9 kJ mol(-1), Delta Delta S(++) = -36 J mol(-1) K(-1), in 80% v/v aqueous ethanol), indicating participation of the double bond in the rate-determining step. Transition structure 1-TS computed at the MP2(fc)/6-31G(d) level of theory revealed that the reaction proceeds through a late transition state with considerably pronounced double bond participation and a substantially cleaved C-Cl bond. The doubly unsaturated compound 3 (1,1-dimethyl-4,8-alkadienyl chloride) solvolyzes with further reduction of the isotope effect, and a drastically lower entropy of activation (k(H)/k(D) = 1.14 +/- 0.01; DeltaS(++) = -152 +/- 12 J mol(-1) K(-1), in 80% v/v aqueous ethanol), suggesting that the solvolysis of 3 proceeds by way of extended pi-participation, i.e., the assistance of both double bonds in the rate-determining step.