Jon K. Hathaway

Factors influencing enantiomeric recognition of primary alkylammonium salts by pyridino-18-crown-6 type ligands

Equilibrium constant (K), enthalpy change (ΔH), and entropy change (ΔS) values were determined for the interactions of a series of chiral pyridino-18-crown-6 type ligands with enantiomers of several primary alkylammonium salts in various solvents. Good enantiomeric recognition in terms of Δ logK was observed in many systems with Δ logK values greater than 0.4. The extent of enantiomeric recognition and the stabilities of the chiral crown ether-ammonium salt complexes were found to depend on the rigidity of the macrocyclic frame of the ligand, the type and arrangement of the donor atoms on the ligand, the bulkiness of the substituents on the ligands chiral centers, the location of the chiral centers on the ligand, and the solvent. The effects of these factors on the extent of enantiomeric recognition and on the stabilities of the complexes were examined for the systems studied.

HPV: Diagnosis, Prevention, and Treatment

Human papilloma virus (HPV) is the most common sexually transmitted disease in the world. Almost 80% of the world’s population is exposed by the age of 50. HPV can cause oropharyngeal, genital, and anal cancers. It also causes genital warts. There is no cure for HPV but vaccines are available to prevent infection by the most common HPV viruses; unfortunately, usage is low. Most people will clear HPV spontaneously. Those who do not are at high risk for developing malignancy. Treatment mainstays are destruction and excision of the lesions.

Experimental basis of cord blood transplantation

Efforts are needed to enhance the efficacy of cord blood (CB) transplantation. Laboratory information set the stage for the first and subsequent CB transplants, and will be instrumental in continuing to advance the field. This paper offers a brief understanding of the current state of hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) biology, a look back at laboratory studies leading to the first CB transplants, and a discussion of the possible means to enhance CB transplantation. Results show that physical recovery of greater numbers of HPCs is possible after CB is collected by perfusing the placenta, but how realistic this procedure is for collection of CB to be banked is open to question. We also show that the chemokine stromal cell-derived factor-1/CXCL12 can enhance the ex vivo expansion of CB HPCs beyond that of the combination of SCF, Flt3-ligand and TPO. Advances in cytokine and stromal cell biology, and in intracellular signals mediating the effects of cytokines/stromal cells should be considered in the context of future efforts to enhance functional activities of donor CB HSCs and HPCs and the microenvironmental niche of the recipient, which is required for acceptance and nurturing these HSCs/HPCs.

Intact Genetic Material is Present in Commercially Processed Cadaver Allografts Used for Pubovaginal Slings

PURPOSE We determined the presence, quantitated the concentration and assessed the length of DNA present in 4 commercially available human cadaver allografts. MATERIALS AND METHODS We evaluated 10 tissue samples from each of 4 commercial sources of human allograft (Mentor Corp., Santa Barbara, California; Musculoskeletal Transplant Foundation, Edison, New Jersey; Regeneration Technologies, Inc., Alachua, Florida; and Life Cell Corp., Woodlands, Texas) for intact DNA segments. All allograft samples underwent a standard extraction technique (proteinase K/sodium dodecyl sulfate/phenol) to isolate genetic material. Spectrophotometry evaluation was done to quantify DNA concentrations. Polymerase chain reaction was performed to amplify the retrieved DNA material. Agarose gel electrophoresis was performed to determine the size of DNA fragments. RESULTS Of the 49 samples tested from all 4 commercial sources of human allograft fascia 39 (97.5%) contained DNA of 400 to 2,000 bp segments. A 400 bp DNA segment was present in 9 Mentor, 10 Musculoskeletal Transplant Foundation, 10 Regeneration Technologies and 10 Life Cell samples. A 700 bp DNA segment was present in 10 Musculoskeletal Transplant Foundation, 10 Regeneration Technologies and 10 Life Cell allografts. A 2,000 bp DNA segment was present in 10 Life Cell tissues. CONCLUSIONS Intact genetic material was present in all 4 commercially processed human allografts. Tissue processing did not completely eliminate intact DNA segments. The size of the intact DNA and the concentration of DNA varied widely based on tissue processing methods.

Is liquid-based pap testing affected by water-based lubricant?

OBJECTIVE: To estimate the effect of water-based lubricant on the liquid-based Pap test. METHODS: Two hundred women each had 2 simultaneous Pap test collections. One specimen was randomly contaminated with 0.5 mL of water-based lubricant after collection. The physician was blinded as to which collection was contaminated. Both specimens were sent for cytology. Cytopathologists were blinded to the study. The rate of abnormal cytology and discordance between the control and the contaminated specimens was estimated. The discordance of secondary diagnoses, such as yeast infections and bacterial vaginosis, was also estimated. RESULTS: The incidence of abnormal cytology was similar in the contaminated specimens and the control specimens (6.5%, 95% confidence interval [CI] 3.5–10.9% versus 7.0%, 95% CI 3.9–11.5%). The rate of disagreement between the 2 specimens collected from each patient was 7.5% (95% CI 4.6–12.1%) and is similar to previously published estimates of discordance using conventional cytology. Secondary diagnoses, such as yeast infections or bacterial vaginosis, were similar in both groups, suggesting no interference from the lubricant. CONCLUSION: Water-based lubricant does not affect liquid-based cervical cytology Pap testing. Water-based lubricant does not affect secondary diagnoses such as bacterial vaginosis or yeast infections. LEVEL OF EVIDENCE: II-1

Enantiomeric recognition of chiral ammonium salts by chiral pyridino- and pyrimidino-18-crown-6 ligands: Effect of structure and solvents

Chiral pyridino- 18-crown-6 ligands interact with chiral primary organic ammonium salts by hydrogen bonding from the ammonium cation to the pyridino nitrogen and two alternate ring oxygen atoms. Enantiomeric recognition in these interactions are caused by the steric bulk of the substituents at chiral macrocycle ring positions. Recognition is best for the interaction of chiral pyridino-18-crown6 hosts with the enantiomers of a-( 1-naphthylethy1)ammonium perchlorate (NapEtHC10,) over (a-phenylethy1)ammonium perchlorate (PhEtHClO,) possibly because of a greater x-x overlap between the naphthalene ring of the guest and pyridine ring of the host. Solvents play an important role in the degree of recognition. A binary solvent composed of 7/3 &H4C12/CH,0H (v/v) gave an enhanced degree of recognition. A new chiral pyrimidino- 18-crown-6 ligand exhibited recognition for the enantiomers of NapEtHC10,.

A thermodynamic study of enantiomeric recognition of organic ammonium cations by pyridino-18-crown-6 type ligands in methanol and a 1: 1 methanol-1,2-dichloroethane mixture at 25.0°C

LogK, ΔH, andTΔS values for interactions of (R) and (S) enantiomers of α-(1-naphthyl)ethylammonium perchlorate (NapEt), α-phenylethylammonium perchlorate (PhEt), and the hydrogen perchlorate salt of 2-amino-2-phenylethanol (PhEtOH) with a series of chiral and achiral pyridino-18-crown-6 type ligands and 18-crown-6 (18C6) were determined from calorimetric titration data valid in methanol and in a 1: 1 (v/v) methanol-1,2-dichloroethane (MeOH-1,2-DCE) mixture at 25.0°C. In the MeOH-1,2-DCE solvent mixture, the chiral macrocyclic ligands exhibit excellent recognition for enantiomers of the three organic ammonium cations as shown by large differences in logK values (Δ logK) which range from 0.4 to 0.6 (2.5- to 4.0-fold difference in binding constants). The Δ logK values in the solvent mixture MeOH-1,2-DCE are increased by 0.1–0.5 logK units over those in absolute methanol, indicating a favorable effect of 1,2-dichloroethane on enantiomeric recognition. In 1,2-dichloroethane, however, the interactions are too strong (logK>6) to observe the degree of recognition by a direct calorimetric method. Complexation of organic ammonium cations by these macrocyclic ligands is driven by favorable enthalpy changes. The entropy changes ure unfavorable in all cases. The thermodynamic origin of enantiomeric recognition for NapEt in 1:1 (v/v) MeOH-1,2-DCE is enthalpic, but those for PhEt and PhEtOH are entropic. Effects of the ligand structure and flexibility and of the organic cation structure on recognition and complex stability are discussed on the basis of the thermodynamic quantities. Different thermodynamic behaviors of achiral 5 and 18C6 from those of chiral macrocyclic ligands indicate a difference between chiral and achiral macrocycle interactions with the chiral organic ammonium cations. The different thermodynamic behavior of NapEt enantiomers compared to those of PhEt and PhEtOH enantiomers supports the idea that the solution complex conformation of NapEt is different from those of PhEt and PhEtOH. π-π interaction is absent for the PhEt and PhEtOH complexes with diesterpyridino-18-crown-6 ligands in solution. Therefore, the higher degree of enantiomeric recognition for NapEt than for either PhEt or PhEtOH by these chiral macrocyclic ligands is a result of the presence of π-π interaction in the NapEt system.

Enantiomeric recognition by chiral pyridino-18-crown-6 for 1-naphthylethylamine. The effect of alkyl substituents on the macrocycle ring

Abstract Molecular recognition of three chiral pyridino-18-crown-6 macrocycles with various dialkyl substituents for (R)- and (S)-α-(1-naphthyl)ethyl]ammonium perchlorate (NapEt) has been determined by isoperibol titration calorimetry and compared to values already determined for the chiral di-methyl- and di-tert-butyl-substituted crowns. Possible mechanisms of recognition for these systems are discussed using the thermodynamic values log K, ΔH, and TΔS. Macrocycles with the bulky substituents tert-butyl, isobutyl, and sec-butyl showed better recognition than those with the less bulky isopropyl and methyl substituents. In the case of macrocycles with bulky substituents, recognition of the enantiomers of NapEt was mainly the result of differences in entropy value changes. With macrocycles having less bulky substituents, reognition was mainly the result of differences in enthalpy value changes.

Transvaginal Adhesiolysis Using Laparoscopic Instruments

Intra-abdominal adhesions are a common complication of abdominal surgery and can lead to further complications including bowel obstruction, infertility, and pain. We describe a novel technique of performing transvaginal laparoscopic lysis of adhesions following a total vaginal hysterectomy in a 41-year-old woman with periumbilical pain and menorrhagia. This natural orifice transluminal endoscopic surgical procedure was tolerated well, did not add considerable overall operating time, and did not require extensive additional training. The patient reported no periumbilical pain at 1 year.