Local Physostigmine in the Management of Early Alcohol Withdrawal

Physostigmine salicylate eyedrops were administered to 15 alcoholic patients suffering from alcohol withdrawal in a double-blind study with placebo washout period prior to active medication. Treatment consisted of one 180 min session with placebo drops—saline chloride which followed trial of same duration with physostigmine salicylate eyedrops. Subjects were evaluated on the serial measurement on the Acute Withdrawal Scale and on the Visual Analog Craving Scale. The results immediately after treatment showed significant symptom reduction following physostigmine administration. It is postulated that the mechanism of physostigmine reversal of withdrawal symptoms may be due to short reversible changes in the reflex responses of the cholinergic hypothalamic neurons.     

Delta opioid receptor selective ligands; DPLPE-deltorphin chimeric peptide analogues†

Further efforts to correlate the topography of the bioactive structures of DPDPE and the deltorphins, two δ-opioid receptor active peptide families, are reported. A number of DPLPE-deltorphin chimeric peptides have been synthesized in which the C-terminal dipeptide δ-address of the deltorphins (-Val-GlyNH₂, -Nle-GlyNH₂) have been linked to the highly δ-opioid selective cyclic peptides DPDPE or DPLPE. These studies demonstrate that a major structural feature determining high potency of hybrid analogues is the chirality of the amino acid residue in position 5. The radioligand binding assays have revealed a decrease in potency (compared to DPDPE) at §-receptors when the C-terminal dipeptides were added to DPDPE. On the other hand, chimeric peptides of DPLPE with these same C-terminal dipeptides retained high δ-selectivity and affinity. Similar results were obtained using the mouse vas deferens (MVD) and guinea pig ileum (GPI) bioassays. The importance of the hydrophilicity of amino acids in positions 2 and 5 for δ-selectivity is consistent with the previous finding for DPLPE and DPDPE. On the other hand, the replacement of phenylalanine-4 with p-chlorophenylalanine-4 did not increase δ-selectivity as in DPDPE. These findings suggest that the δ-receptor interacts with hybridized enkephalins and deltorphins somewhat differently than with DPDPE.     

The association of –262C/T polymorphism in the catalase gene and delayed graft function of kidney allografts

Background: Catalase is an intracellular antioxidant enzyme that is mainly located in cellular peroxisomes and in the cytosol. This enzyme plays a significant role in the development of tolerance to oxidative stress in the adaptive response of cells and tissues. The aim of the present study was to examine the association between the –262C/T polymorphism in the catalase gene and delayed graft function (DGF), acute rejection and chronic allograft nephropathy of kidney allografts. Methods: One hundred eighty‐seven recipients of first renal transplants were included in the study. The histories of the patients were analysed regarding DGF, acute rejection and chronic allograft nephropathy. The polymorphism –262C/T in the catalase gene was analysed using the polymerase chain reaction – restriction fragment length polymorphism (PCR‐RFLP) method. Results: The risk of DGF was significantly lower in T allele carriers compared with CC homozygotes: odds ratio = 0.34, 95% confidence interval = 0.17–0.67, P = 0.001. There were no statistically significant associations between the studied polymorphism and acute rejection or chronic allograft nephropathy. Conclusion: The results of this study suggest that –262C/T polymorphism in the catalase gene is associated with DGF in kidney allograft recipients.     

Lipid membrane permeability of modified c[D-Pen2, D-pen5]enkephalin peptides

Permeability coefficients of a series of analogues of a potent opioid peptide, c[D-Pen², D-Pen⁵]enkephalin, were measured in a model membrane system. The analogues included hydrophobic amino acid substitutions on position 3. Liposomes of a mixed composition consisting of zwitterionic lipids and cholesterol served as the model membranes. The obtained permeability coefficients range between 0.38 × 10^?12 and 2.9 × l0^?12 cm/s. These data were correlated with the hydrophobicity scale of Nozaki and Tanford (J. Biol. Chem. 246, 1971, 2211-2217) (correlation coefficient = 0.9933) and with determinations of lipid order perturbation by differential scanning calorimetry (correlation coefficient = -0.9779). The reasonably good correlation obtained within the family of analogues substituted on position 3 (Gly, Ala, Leu, Phe) indicates that changes in permeabilities are primarily related to increases in the partition coefficient of the peptide. However, Phe residue added on the N-terminal end of the peptide (position 0) does not appear to follow the observed trend, showing stronger lipid perturbation and lower permeability compared to the Phe³ analog. This observation demonstrates that each class of peptide modifications requires a new basis of permeability analysis and predictions. © Munksgaard 1996.     

Ablation of Severe Drug‐Resistant Tachyarrhythmia During Pregnancy

Ablation of Tachyarrhythmia During Pregnancy. Aims: The goal of this study was to describe mapping and ablation of severe arrhythmias during pregnancy, with minimum or no X‐ray exposure. Treatment of tachyarrhythmia in pregnancy is a clinical problem. Pharmacotherapy entails a risk of adverse effects and is unsuccessful in some patients. Radiofrequency ablation has been performed rarely, because of fetal X‐ray exposure and potential maternal and fetus complications. Group and Method: Mapping and ablation was performed in 9 women (age 24–34 years) at 12–38th week of pregnancy. Three had permanent junctional reciprocating tachycardia, and 2 had incessant atrial tachycardia. Four of them had left ventricular ejection fraction ≤45%. One patient had atrioventricular nodal reciprocating tachycardia requiring cardioversion. Three patients had Wolff‐Parkinson‐White syndrome. Two of them had atrial fibrillation with ventricular rate 300 bpm and 1 had atrioventricular tachycardia 300 bpm. Fetal echocardiography was performed before and after the procedure. Results: Three women had an electroanatomic map and ablation done without X‐ray exposure. The mean fluoroscopy time in the whole group was 42 ± 37 seconds. The mean procedure time was 56 ± 18 minutes. After the procedure, all women and fetuses were in good condition. After a mean period of 43 ± 23 months follow up (FU), all patients were free of arrhythmia without complications related to ablation either in the mothers or children. Conclusion: Ablation can be performed safely with no or minimal radiation exposure during pregnancy. In the setting of malignant, drug‐resistant arrhythmia, ablation may be considered a therapeutic option in selected cases. (J Cardiovasc Electrophysiol, Vol. 21, pp. 877‐882, August 2010)     

Apoptosis of T Cells in the First Trimester Human Decidua

PROBLEM: Apoptosis has been accepted as a mechanism for maintaining tolerance in the immune system. The induction of apoptotic cell death can also be a possible outcome of the lymphocyte activation. Expression of Fas ligand (FasL) by the human trophoblast has been proposed as a mechanism providing protection against the lytic action of decidual immune cells. The aim of this study was to determine whether decidual T cells undergo apoptosis during abortion. METHOD OF STUDY: We studied apoptosis of T cells isolated from the first-trimester decidua in 12 women after spontaneous or elective abortion. We used gel electrophoresis to detect DNA fragmentation. Cells undergoing DNA fragmentation also were identified by DNA analysis using flow cytometry. This method was based on the accumulation of ethanol-fixed apoptotic cells in the sub-GO/G1 peak of the DNA content as a result of the loss of DNA fragments from the cells and because of a reduced DNA ability to be stained by propidium iodide. In addition, the expression of Fas antigen on the surface of decidual T cells (CD3⁺) also was determined. RESULTS: We did not detect apoptosis by the “ladder” technique. However, the apoptotic index (the percentage of positive cells per total number of cells) ranged from 2% to 24% using flow cytometry. CONCLUSIONS: Trophoblast cells usually fail to stimulate alloantigen-specific T cells, but they may express nonclassical major histocompatibility complex alloantigens to which mothers can produce immunoglobulin G alloantibody, which requires T helper cell activation. The apoptosis of T cells in the human decidua, probably through Fas-FasL signaling, may be a defense mechanism against rejection of the fetal allograft by the maternal immune system.     

The Importance of Decalcification in the Treatment of Tuberculosis I. The Influence of Decalcification in the Course of Healing in Experimental Tuberculosis in Guinea pigs1

The authors have the opinion that hypercalcification of the morbid pulmonary tissue in destructive pulmonary tuberculosis impedes the requisite penetration by the therapeutic agents employed. Experiments were made on guinea pigs, one group receiving antibiotics together with chemical compounds of the EDTA type having a decalcifying effect, while a second group received calcifying agents as well as therapeutic drugs. For control, a third group was treated solely with streptomycin and isoniazid. Chemical, anatomicopathological and histopathological tests provided criteria for evaluation. The best therapeutic results were obtained in the group of decalcified animals.