Separation of D-forms and L-forms of DL-aspartic acid derivatives by the enzyme subtilisin DY

The ability of the enzyme subtilisin DY for the synthesis of derivatives of DL-aspartic acid which are differently N and C-terminal protected and semiproducts of the peptide synthesis was investigated. The enzyme reaction was characterized by high yields and a comparatively short reaction time. Two of the substrates, Z-D,L-Asp-(OMe)₂ and PhAc-D,L-Asp-(OMe)₂, were hydrolyzed for about 15 min; the reaction time for Boc-D,L-Asp-(OMe)₂ was 2.5 h. The values for the MICHAELIS constants obtained for Z-D,L-Asp-(OMe)₂ (K_m = 0.576 mM) and PhAc-D,L-Asp-(OMe)₂ (K_m = 0.300 mM) showed a high affinity of the enzyme to the substrates. For Boc-D,L-Asp-(OMe)₂ the affinity of the enzyme is considerable lower (K_m = 14.07 mM). The results of these investigations can be effectively used for the separation of N-protected derivatives of D,L-aspartic acid and with a high probability also for other amino and racemic forms.     

Application of MR spectroscopy and treatment approaches in a patient with extrapituitary growth hormone secreting macroadenoma

MR spectroscopy (MRS) of hormonally active pituitary adenomas has not been published in literature. We report MR imaging and spectroscopy findings in a 41-year-old man with extrapituitary growth hormone-secreting adenoma. Application of the single voxel proton MRS, SE 135 technique, with voxel size 11x11x11 mm, revealed the elevated choline peak (resonance at 3.2 ppm) in the paramedial aspect of the tumor, while no metabolic activity in the mentioned region was noted using the same method 11 months after Lanreotide treatment. Elevation of choline peak in functional pituitary adenomas could represent an active marker of cellular proliferation, compatible with increased hormonal activity.     

Effects of clonidine preemptive analgesia on acute postoperative pain in abdominal surgery

Preemptive analgesia refers to blockade of afferent nerve fibers before a painful stimulus, which prevents or reduces subsequent pain even beyond the effect of the block. The aim of the study was to compare the effect of clonidine used before and at the end of operation on pain control in abdominal surgery. A total of 77 patients admitted for colorectal surgery were randomly classified into three groups: epidural clonidine before operation, epidural clonidine at the end of operation, and control group. After the operation on patient demand, analgesia with boluses of epidural morphine was instituted. The parameters of postoperative pain level using VAS score (visual analog scale), sedation and analgesics consumption were determined as outcome measures at 1, 2, 6, and 24 h of the operation. Clonidine administered before operation provided lowest pain scores at 6 and 24 h (p < 0.05). Clonidine administered at the end of operation had low pain scores at 1 and 2 h, with a significant pain breakthrough thereafter (6.93 +/- 1.66 at 6 h and 4.04 +/- 2.39 at 24 h) compared with the group administered clonidine before operation (3.60 +/- 2.94 and 3.71 +/- 1.82). Clonidine administered before operation provided less sedation (p < 0.05) and a significantly lower use of analgesics (p < 0.05). Blockade of nociceptive stimulus using the centrally acting alpha2-adrenergic agonist clonidine before the onset of pain stimulus resulted in reduced pain levels, sedation and analgesic requirement.     

Synthesis and biological study of new galanthamine-peptide derivatives designed for prevention and treatment of Alzheimer’s disease

Amino Acids - The Alzheimer’s disease leads to neurodegenerative processes and affecting negatively million people worldwide. The treatment of the disease is still difficult and incomplete in...     

Treatment of rapid cycling bipolar disorders

Rapid cycling (RC) bipolar disorder is defined as four or more affective episodes within one year. RC bipolar disorder constitutes one of the most difficult forms of the illness to treat effectively. According to several studies, RC bipolar patients have more severe symptoms than non-rapid cycling bipolar patients. Most studies indicate that only 10% to 20% of patients with bipolar disorders experience rapid cycling, but this is of great concern to psychiatrists because of its association with treatment refractoriness. Second generation antipsychotics are increasingly being used in the treatment of bipolar disorder. A first step in the management of rapid-cycling bipolar disorder is the thorough assessment of possible medications or environmental factors that may destabilize the disorder and contribute to the recurrence of episodes, increasing cycle frequency, or both. All currently approved antidepressant drugs pose some risk of mood destabilization, but the risk is highest for tricyclic antidepressants. Discontinuation of antidepressants should be the first step in the management of RC patients.     

Bacterial adhesion to sulcular epithelium in periodontitis

The purpose of this study was to investigate, by electron microscopy, the type of bacterial attachment to the sulcular epithelium in periodontitis. Gingiva biopsies were observed in a transmission electron microscope using cytochemical staining with ruthenium red for glycocalyx visualisation. In addition, subgingival plaque samples and biopsies from the sulcular epithelium in periodontitis from the patients were estimated microbiologically. Aerobic bacteria only were estimated in the subgingival plaque and both aerobic and anaerobic bacteria in the gingival biopsies. No bacterial internalisation could be observed. Fimbria-mediated adhesion as the only type of bacterial attachment and a large diversity of bacterial glycocalyces were detected. As the fimbrial adhesins of putative periodontal pathogens are able in vitro to induce inflammation and bone resorption via stimulation of the proinflammatory cytokine production, the demonstrated fimbrial adhesins suggest the significant role of bacterial adhesion to sulcular epithelium in periodontitis.     

SAR around (l)-S-adenosyl-l-homocysteine,an inhibitor of human DNA methyltransferase (DNMT) enzymes

The inhibitory activity of base-modified SAH analogues and the specificity of inhibiting human DNMT1 and DNMT3b2 enzymes was explored. The 6-amino group was essential while the 7-N of the adenine ring of SAH could be replaced by CH– without loss of activity against both enzymes. The introduction of small groups at the 2-position of the adenine moiety favors DNMT1 over DNMT3b2 inhibition whereas alkylation of the N⁶-amino moiety favors the inhibition of DNMT3b2 enzyme.     

Constrained (l-)-S-adenosyl-l-homocysteine (SAH) analogues as DNA methyltransferase inhibitors

Potent SAH analogues with constrained homocysteine units have been designed and synthesized as inhibitors of human DNMT enzymes. The five membered (2S,4S)-4-mercaptopyrrolidine-2-carboxylic acid, in 1a, was a good replacement for homocysteine, while the corresponding six-member counterpart was less active. Further optimization of 1a, changed the selectivity profile of these inhibitors. A Chloro substituent at the 2-position of 1a, compound 1d, retained potency against DNMT1, while N⁶ alkylation, compound 7a, conserved DNMT3b2 activity. The concomitant substitutions of 1a at both 2- and N⁶ positions reduced activity against both enzymes.