NMR and X-ray crystallographic studies on cyclic tetrapeptide,cyclo (D-Phe-Pro-Sar-Gly)

The conformation of the synthetic cyclic tetrapeptide cyclo (D-Phe-Pro-Sar-Gly) has been determined in solution using the nuclear magnetic resonance technique and in the crystal state by X-ray crystallography. Results showed that the peptide exhibited two different conformations in solution, conformer 1 having cis-trans-cis-trans peptide bonds and conformer 2 having trans-cis-trans-cis peptide bonds. No intramolecular hydrogen bonds were observed in the structures. The X-ray diffraction studies showed the crystals to be orthorhombic with space group P2₁2₁2₁ with unit-cell dimensions, a = 5.790, b= 10.344, c = 31.446 Å, Z=4, R= 0.104 for 2301 observed reflections. The crystal structure showed only one type of conformer having cis-trans-cis-trans peptide bonds similar to the conformer 1 in solution. © Munksgaard 1996.     

Conformational studies of a synthetic cyclic decapeptide fragment of rat transforming growth factor-α

The solution conformation of a synthetic cyclic decapeptide [with sequence mimicking the third disulfide loop of rat transforming growth factor-α (rTGF-α)] in deuterated dimethyl sulfoxide was studied by 2D NMR. The determination of solution structures was based on NOE interproton distances, using a combination of distance geometry and simulated annealing protocols. The convergence of the selected structures was evident from the small atomic pairwise root-mean-square deviation values among them. Good agreement was noted between the experimental and simulated NOESY spectra, thereby reflecting the accuracy of the calculated solution structures. Analysis of the structures indicates that the residues Tyr5 and Arg9 exhibit similar side chain orientation as that in the corresponding disulfide loop of human transforming growth factor-α.     

REPAIR OF THE QUADRICEPS APPARATUS FOLLOWING PATELLECTOMY IN RECENT FRACTURES OF THE PATELLA: A NEW TECHNIQUE,WITH RESULTS1

The importance of “double tourniquet” technique in repair of the quadriceps mechanism after total patellectomy in recent fractures of the patella is described and its advantages are discussed. The results following this method of repair in 17 total patellectomies have been studied and discussed.     

X-ray studies on crystalline complexes involving amino acids and peptides

L-Arginine acetate crystallizes in the monoclinic space group P2¹ with a = 9.229(2), b = 5.178(3), c = 13.271(4) Å and β= 111.4(1)d?. The crystal structure was solved by direct methods and refined to an R value of 0.058 for 1333 observed reflections. The conformation of the arginine molecules in the crystal is different from those observed in the crystals of L-arginine, its salts and complexes. The crystal structure indicates that complexation with a small carboxylic acid like acetic acid is sufficient to align arginine molecules in a head-to-tail fashion. The structure contains a specific ion-pair interaction, involving electrostatic attraction as well as two nearly parallel, N-H. O hydrogen bonds, between the guanidyl group and the acetate ion.     

Unilateral groin surgery in children: will the addition of an ultrasound‐guided ilioinguinal nerve block enhance the duration of analgesia of a single‐shot caudal block?

Background: Inguinal hernia repair, hydrocelectomy, and orchidopexy are commonly performed surgical procedures in children. Postoperative pain control is usually provided with a single‐shot caudal block. Blockade of the ilioinguinal nerve may lead to additional analgesia. The aim of this double‐blind, randomized controlled trial was to evaluate the efficacy of an adjuvant blockade of the ilioinguinal nerve using ultrasound (US) guidance at the end of the procedure with local anesthetic vs normal saline and to explore the potential for prolongation of analgesia with decreased need for postoperative pain medication. Methods: Fifty children ages 1–6 years scheduled for unilateral inguinal hernia repair, hydrocelectomy, orchidopexy, or orchiectomy were prospectively randomized into one of two groups: Group S that received an US‐guided ilioinguinal nerve block with 0.1 ml·kg^?1 of preservative‐free normal saline and Group B that received an US‐guided nerve block with 0.1 ml·kg^?1 of 0.25% bupivacaine with 1 : 200 000 epinephrine at the conclusion of the surgery. After induction of anesthesia but prior to surgical incision, all patients received caudal anesthesia with 0.7 ml·kg^?1 of 0.125% bupivacaine with 1 : 200 000 epinephrine. Patients were observed by a blinded observer for (i) pain scores using the Children and Infants Postoperative Pain Scale, (ii) need for rescue medication in the PACU, (iii) need for oral pain medications given by the parents at home. Results: Forty‐eight patients, consisting of 46 males and two females, with a mean age of 3.98 (sd ± 1.88) were enrolled in the study. Two patients were excluded from the study because of study protocol violation and/or alteration in surgical procedure. The average pain scores reported for the entire duration spent in the recovery room for the caudal and caudal/ilioinguinal block groups were 1.92 (sd ± 1.59) and 1.18 (sd ± 1.31), respectively. The average pain score difference was 0.72 (sd ± 0.58) and was statistically significant (P < 0.05). In addition, when examined by procedure type, it was found that the difference in the average pain scores between the caudal and caudal/ilioinguinal block groups was statistically significant for the inguinal hernia repair patients (P < 0.05) but not for the other groin surgery patients (P = 0.13). For all groin surgery patients, six of the 23 patients in the caudal group and eight of the 25 patients in the caudal/ilioinguinal block group required pain rescue medications throughout their entire hospital stay or at home (P = 0.76). Overall, the caudal group received an average of 0.54 (sd ± 1.14) pain rescue medication doses, while the caudal/ilioinguinal block group received an average of 0.77 (sd ± 1.70) pain rescue medication doses; this was, however, not statistically significant (P = 0.58). Conclusions: The addition of an US‐guided ilioinguinal nerve block to a single‐shot caudal block decreases the severity of pain experienced by pediatric groin surgery patients. The decrease in pain scores were particularly pronounced in inguinal hernia repair patients.     

Prevalence rates and risk factors for hepatitis C among drug users not in treatment in Malaysia

Introduction and Aims. The prevalence of hepatitis C virus (HCV) among heroin dependants in treatment was estimated at 89.9%; however, virtually no information exists on the prevalence or risk behaviour among the larger population of drug users not in treatment. This study assessed the prevalence of HCV and associated risk factors among this group with a view to designing more effective intervention programs. Design and Methods. A cross‐sectional survey of 552 not‐in‐treatment drug users recruited from five key urban centres across peninsular Malaysia with on‐site serological testing for HCV and HIV seropositivity was conducted. Results. HCV prevalence was 65.4% for the overall sample, but higher among injecting drug users (67.1%) relative to non‐injecting drug users (30.8%). Bivariate analysis suggested seven risk factors though only sharing injecting paraphernalia and lifetime homosexual/bisexual behaviour remained significant in multivariate analysis. Discussion and Conclusions. With the majority (65.9%) sharing injecting equipment and about the same proportion (65.4%) being HCV positive, the risk of further transmission to new drug users is high. It is imperative that the nascent needle and syringe exchange and condom distribution program and its ancillary services—launched in 2005 to fight HIV—be fine tuned, as a first step, to control HCV. With its greater infectivity and non‐symptomatic character, HCV is more insidious. Given the shared risk factors of HCV and HIV, routine screening of drug users for HCV—currently non‐existent—should be instituted. This, with other intervention measures, will help detect and control HCV at an earlier stage while also checking the spread of HIV.[Vicknasingam B, Narayanan S, Navaratnam V. Prevalence rates and risk factors for hepatitis C among drug users not in treatment in Malaysia. Drug Alcohol Rev 2009;28:447–454]     

X-Ray studies on crystalline complexes involving a mino acids and peptides

L-Histidine acetate crystallizes in two forms: (I) orthorhombic; P2₁2₁2₁; a= 5.027, b= 11.126, c= 17.473 Å; Z = 4; (II) monoclinic; C2; a= 15.649, b= 9.276, c= 8.566 Å; β= 94.65°; Z = 4. The structures were solved by direct methods and refined to R-values of 0.056 and 0.089 for 1131 and 1330 observed reflections, respectively. The conformations of the histidine molecule in the two forms are different. However, both are such that they facilitate the occurrence of a specific interaction of the histidine molecule with a carboxylate group. The basic elements of aggregation are hydrogen-bonded histidine ribbons, but they are of different types in the two structures. The ribbons are interconnected by acetate ions to form the crystals. The structures contain two characteristic interaction patterns involving amino and carboxylate groups, one of which is observed for the first time. The two water molecules in form II and their symmetry equivalents form an uninterrupted hydrogen-bonded chain running through the crystal. They also present an interesting case of disorder in hydrogen bonds. A comparative study involving amino acid complexes of acetic acid shows that the presence of acetate ion could lead to new aggregation patterns, specific interactions and characteristic interaction patterns with varying degrees of similarity with those observed in other structures containing amino acids.     

X-ray studies on crystalline complexes involving amino acids and peptides

l -Lysine d -glutamate crystallizes in the monoclinic space group P2₁ with a= 4.902, b= 30.719. c= 9.679 Å. β= 90° and Z = 4. The crystals of l -lysine d -aspartate monohydrate belong to the orthorhombic space group P2₁2₁2₁ with a= 5.458, b= 7.152, c= 36.022 Å and Z = 4. The structures were solved by the direct methods and refined to R values of 0.125 and 0.040 respectively for 1412 and 1503 observed reflections. The glutamate complex is highly pseudosymmetric. The lysine molecules in it assume a conformation with the side chain staggered between the α-amino and the α-carboxylate groups. The interactions of the side chain amino groups of lysine in the two complexes are such that they form infinite sequences containing alternating amino and carboxylate groups. The molecular aggregation in the glutamate complex is very similar to that observed in l -arginine d -aspartate and l -arginine d -glutamate trihydrate, with the formation of double layers consisting of both types of molecules. In contrast to the situation in the other three ld complexes, the unlike molecules in l -lysine d -aspartate monohydrate aggregate into alternating layers as in the case of most ll complexes. The arrangement of molecules in the lysine layer is nearly the same as in l -lysine l -aspartate, with head-to-tail sequences as the central feature. The arrangement of aspartate ions in the layers containing them is, however, somewhat unusual. Thus the comparison between the ll and the ld complexes analyzed so far indicates that the reversal of chirality of one of the components in a complex leads to profound changes in molecular aggregation, but these changes could be of more than one type.     

Anaesthetic management of insulinoma

The anaesthetic management of two cases of insulinoma treated by distal pancreatectomy is presented. Stress is laid on pre-operative and intra-operative glucose administration in sufficiently high quantity. Pre-operative corticosteroid therapy is better avoided. Dextrose infusion should be stopped soon after removal of the tumour to prevent excessive hyperglycemic response in the postoperative period. Methyoxyflurane was used because it tends to raise the blood sugar level. Pancuronium bromide was preferred because of the stable cardiovascular conditions it produces.