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PubMed2005

Prolongation of pentoxifylline aliphatic side chain positively affects the reversal of P-glycoprotein-mediated multidrug resistance in L1210/VCR line cells.

We reported previously that derivatives of pentoxifylline (PTX) reverse multidrug resistance (MDR) in P-glycoprotein (P-gp) positive L1210/VCR cells. Based on the results of a recent study using 25 N-alkylated methylxanthines with carbohydrate side-chains of various lengths, we formulated the following design criteria for a methylxanthine molecule to effectively reverse P-gp mediated MDR: i) a massive substituent at the N1 position is crucial for MDR reversal potency; ii) elongation of the substituents at the N3 and N7 positions (from methyl to propyl) increases the efficacy of a xanthine to reverse MDR; iii) elongation of the substituent at the C8 position (from H to propyl) decreases the efficacy of a xanthine to reverse MDR. Based on these criteria, we synthesized and tested for potency to reverse MDR a new PTX derivative, 1-(10-undecylenyl)-3-heptyl-7-methyl xanthine (PTX-UHM), with prolonged substituents at the N1 and N3 positions. The derivative was obtained by alkylation of 3-heptyl-7-methyl xanthine with 1-methylsulfonyloxy-10-undecylenyl. NMR and IR structural analyses proved the identity of the product. Cytotoxicity study showed that PTX-UHM is only slightly more toxic to L1210/VCR cells than PTX. We found that both PTX-UHM and PTX were able to reverse vincristine resistance of L1210/VCR cells, yet PTX-UHM was significantly more efficient in the reversal than PTX.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1990

Two pyridine analogues with more effective ability to reverse multidrug resistance and with lower calcium channel blocking activity than their dihydropyridine counterparts.

Four pyridine analogues and their dihydropyridine counterparts were examined for their ability to reverse drug resistance in a multidrug-resistant human carcinoma cell line, KB-C2. Two pyridine analogues were more able to reverse drug resistance than their dihydropyridine counterparts. The other two pyridine analogues had an effect on drug resistance similar to their dihydropyridine counterparts. The calcium channel-blocking activity of all the pyridine analogues was considerably lower than that of the dihydropyridine analogues. Of the pyridine analogues, 2-[4-(diphenylmethyl)-1-piperazinyl]ethyl 5-(trans-4,6-dimethyl-1,3,2-dioxaphosphorinan-2-yl)-2,6-dimethyl-4 -(3- nitrophenyl)-3-pyridinecarboxylate P-oxide (PAK-104P) was the most effective in reversing multidrug resistance. PAK-104P (1 and 5 microM) completely reversed the drug resistance in KB-8-5 and KB-C2 cells, respectively. The reversing effect of PAK-104P was greater than that of other multidrug resistance-reversing agents, cepharanthine, verapamil, nimodipine, and nicardipine. PAK-104P at 1 microM increased about 10-fold the accumulation of vinblastine in KB-C2 cells, whereas verapamil at the same concentration increased the accumulation about 2-fold. The inhibition of [3H]azidopine photolabeling of P-glycoprotein by the pyridine and dihydropyridine analogues except 2-[methyl(phenyl-methyl)amino]ethyl 4-(2-chlorophenyl)-5-(4-methyl-1,3,2-dioxaphosphorinan-2-yl)-1,4-d ihydro-2,6- dimethyl-3-pyridinecarboxylate P-oxide correlated with the reversing of drug resistance by the analogues. Some newly synthesized pyridine analogues seemed to have lower calcium channel-blocking activity and more potent resistance-reversing ability than verapamil and other calcium channel blockers.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Solutol HS 15, nontoxic polyoxyethylene esters of 12-hydroxystearic acid, reverses multidrug resistance.

A recently developed non-ionic surfactant called Solutol HS 15 (poly-oxyethylene esters of 12-hydroxystearic acid), with low toxicity in vivo, was shown to reverse completely the multidrug resistance of KB 8-5 and KB 8-5-11 human epidermoid carcinoma cells in vitro but did not potentiate drug toxicity in drug-sensitive KB 3-1 cells. At a concentration of 10% of its own IC50 (mean concentration of drug that causes 50% inhibition of cell growth compared to controls), Solutol HS 15 produced a 35-, 28-, and 42-fold reduction in the resistance of KB 8-5-11 cells to colchicine, vinblastine, and doxorubicin, respectively. Solutol HS 15 was relatively much more potent than the prototypic reversing agent, verapamil, for reversing colchicine resistance, compared to the ability of each agent to reverse colchicine resistance, compared to the ability of each agent to reverse vinblastine resistance. Like verapamil, Solutol HS 15 promoted a 50-fold accumulation of rhodamine 123 in KB 8-5-11 cells, as measured by flow cytometry. Also, Solutol HS 15 and verapamil reduced the efflux of rhodamine 123 from KB 8-5-11 cells previously loaded with rhodamine 123 to a similar low rate. Solutol HS 15 did not affect the transport of alanine or glucose into KB 8-5-11 cells, indicating that its effect upon membrane active transport is not entirely nonspecific. Considering their different structure and different relative potency for reversing colchicine resistance, Solutol HS 15 and verapamil probably reverse multidrug resistance by different mechanisms. Solutol HS 15 merits consideration as a potential therapeutic agent because of its effectiveness for reversing multidrug resistance in vitro and its low toxicity in vivo.

Carcinoma, Squamous Cell↗
PubMed1990

Comparison of in-situ and reversed saphenous vein grafts for infrageniculate bypass.

Current controversy surrounding in-situ and reversed saphenous vein grafts prompted a review of 161 procedures performed between 1982 and 1987. Analysis was based on objective criteria recommended by the Society for Vascular Surgery/International Society for Cardiovascular Surgery (SVS/ISCVS) Committee on Reporting Standards. There were 92 in-situ bypasses, 42 to the popliteal artery below the knee, and 50 to tibial vessels; of 69 reversed vein grafts, the comparable figures were 51 and 18. Sixty-seven in-situ and 43 reversed grafts were done for foot salvage. The overall primary patency rate for in-situ grafts was 81.1% at 30 days, 77.0% at 1 year, 74.7% at 3 years and 59.8% at 5 years; corresponding reversed vein patency rates were 85.2%, 76.8%, 67.0% and 42.3%. Patency rates for foot salvage for in-situ grafts were 81.7% at 1 month, 75.9% at 1 year and 72.6% at 3 years, and for reversed vein grafts 78.6%, 70.3% and 66.5%. Secondary patency rates were 72.8% at 3 years for in-situ vein and 67.2% for reversed vein; the foot-salvage rate at 3 years was 91.0% with in-situ vein and 78.9% with reversed vein. The study demonstrated no statistically significant difference between in-situ and reversed saphenous vein bypass for infrageniculate reconstruction, regardless of the distal anastomotic site or severity of disease. Although a trend favouring the in-situ technique was noted, particularly at the tibial level, longer follow-up and a prospective randomized trial is needed to evaluate this.

Aged↗
PubMedDate not supplied

Reversal sign on CT: effect of anoxic/ischemic cerebral injury in children.

A retrospective study was performed to determine the clinical and pathologic features, etiology, and outcome of children with the reversal sign. The reversal sign, a striking CT finding, probably represents a diffuse, anoxic/ischemic cerebral injury. CT features of the reversal sign are diffusely decreased density of cerebral cortical gray and white matter with a decreased or lost gray/white matter interface, or reversal of the gray/white matter densities and relatively increased density of the thalami, brainstem, and cerebellum. Twenty children with the reversal sign were retrospectively analyzed. We divided the patients into three groups: (1) acute reversal, (2) intermediate group, and (3) chronic reversal. There were nine cases of trauma (seven of child abuse); nine hypoxia/anoxia incidents (birth asphyxia, drowning, status epilepticus); one bacterial meningitis; and one degenerative encephalitis. All acute- and intermediate-group patients had respiratory problems requiring ventilator support and intensive care. In five of seven patients who died, autopsy findings were consistent with anoxic/ischemic encephalopathy. Surviving patients have profound neurologic deficits with severe developmental delay. The CT reversal sign carries a poor prognosis and indicates irreversible brain damage.

Brain↗
PubMed1989

[Mandibular movement and electromyogram investigation of normal occlusion and reversed occlusion before and after correction of over jet].

The purpose of this investigation was to understand how the mandibular movement and myofunction in reversed occlusion, approach to normal occlusion after the correction of over jet. The experiment was carried out in 30 normal and 26 reversed occlusion school children patients who were classified into 3 groups by morphological analysis. A K6 diagnostic system was used. It recorded muscle activity of maximum clenching, free way space, path of closure, and the maximum velocity of opening and closing mandibular. And recorded a condylar test at the same time. Reversed occlusion classified 3 groups: upper and lower incisor had improper inclinations (D group, 19%), construction bite possible but recognized back and forth discrepancy between maxilla and mandibular (FS group, 50%), discrepancy larger than FS group and construction bite not possible (S group, 31%). Toward upper forth group indicated 77% and toward upper back group indicated 23% in normal occlusion. As for reversed occlusion the former indicated 92% and the latter indicated 8%. Differences in connection with orthodontic appliance and period of treatment were not so large. Back and forth mandibular movement, as measured by a condylar test, was greater for reversed occlusion than for normal occlusion, but this value tended to decrease after orthodontic treatment. In reversed occlusion, maximum opening, free way space, maximum velocity of opening and closing and muscle activity of rest position didn't show significant difference (p less than 0.05) among each group before and after the correction of over jet. Temporalis and masseter activity of maximum clenching, except temporalis among the D group, approached the values for normal occlusion. In the S group, muscle activity of maximum clenching with a cotton-roll, was lower before treatment, but approached to data in normal occlusion. These results prove that improvement of over jet in reversed occlusion, by ordinary orthodontal diagnosis and treatment plan, quasi-normalizes mandibular movement and muscle activity in reversed occlusion.

Child↗
PubMed1986

[Reverse redistribution in dipyridamole-loading thallium-201 images using single photon emission computed tomography].

This study demonstrated the clinical significance of reverse redistribution, i.e., a decrease in the relative Tl activity in the redistribution image compared to that of the stress image after administration of dipyridamole. Dipyridamole was infused intravenously at a rate of 0.142 mg/kg per min for four min, and a stress image was obtained 10 min after the injection of two mCi 201Tl. Each patient returned for redistribution scanning in the identical position three hours after the isotope injection. The myocardial image of Tl was analyzed by single photon emission computed tomography and its washout rate was calculated by the segmental ROI method. Myocardial function and the motion of left ventricular wall were analyzed by 99mTc-RBC-gated cardiac pool imaging. The results were as follows: Reverse redistribution was noted in 27 (21.6%) of 125 consecutive Tl dipyridamole and redistribution myocardial imaging studies. The stress image demonstrated normal perfusion (group 1) and reduced perfusion (group 2) of Tl. Group 1 consisted of 17 patients with diabetes mellitus, supraventricular arrhythmias, hypertension, and others. Group 2 consisted of 10 patients with subendocardial infarction, diabetes mellitus, and hypertension, and others. The percentage prevalence of reverse redistribution among patients with supraventricular arrhythmia was 62.5% (five of eight patients), with subendocardial infarction 60.0% (three of five), with hypertension 42.8% (six of 14), and with diabetes mellitus 40.0% (eight of 20), while in those with transmyocardial infarction and angina pectoris no reverse redistribution percentage was found. The washout rate of Tl in normal perfusion areas was 44.0 +/- 12.8%, the reverse redistribution of group 1 was 47.4 +/- 12.8%, and of group 2 was 51.2 +/- 8.2%. The washout rate of the reverse redistribution of group 2 was significantly greater than that of the normal areas. In gated cardiac pool imaging, patients in group 2 had significantly larger areas showing abnormal contraction of the left ventricular wall and significantly lower ejection fraction than did group 1. In the electrocardiogram ST segment depression was noted more frequently in group 2 than group 1. No Q wave was present in the corresponding reverse redistribution area. These results suggest that reverse redistribution might occur in a region with a combination of scarred and normal myocardium, the metabolically affected myocardium, and an area with relatively increased myocardial blood flow. The patients in group 2 seem to have the more pathological myocardium than do those in group 1.

Adult↗
PubMed1986

Reverse reaction of smooth muscle myosin light chain kinase. Formation of ATP from phosphorylated light chain plus ADP.

Incubation of smooth muscle phosphorylated heavy meromyosin in the presence of myosin light chain kinase, calmodulin, ADP, and Ca2+ results in a decrease of the protein-bound phosphate. The dephosphorylation is not due to phosphatase activity and is dependent on the presence of ADP and the active ternary myosin light chain kinase complex. Using 32P-labeled phosphorylated 20,000-dalton light chains as the phosphate donor, the formation of ATP from ADP can be demonstrated. This reaction requires the presence of Ca2+, calmodulin, and myosin light chain kinase. These results indicate that myosin light chain kinase can catalyze a reverse reaction and form ATP from ADP and phosphorylated substrate. The rate of the reverse reaction, kcat/KLC approximately 0.21 min-1 microM-1, is considerably slower than the forward reaction under similar conditions and is therefore detectable only at relatively high concentrations of myosin light chain kinase. For the reverse reaction, KmADP is approximately 30 microM and ATP is a competitive inhibitor, KIATP approximately 88 microM. For the forward reaction, measured with both isolated light chains and intact myosin, KmATP is approximately 100 microM and ADP is a competitive inhibitor, KiADP approximately 140 microM (myosin) and 120 microM (light chains). Thus, the affinity of ATP for the forward and reverse reactions is similar, but the affinity of ADP is higher for the reverse reaction. From the light chain dependence of the two reactions, the following was calculated: forward, Km = 5 microM, kcat = 1720 min-1, and reverse, Km = 130 microM, kcat = 27 min-1. In contrast to the data obtained with isolated light chains, it is suggested that, with intact myosin as substrate, the Km term is primarily responsible for determining the rate of the reverse reaction. With light chains phosphorylated at serine 19 and threonine 18, it was shown that both sites act as a phosphate donor, although the reverse reaction for threonine 18 is slower than that for serine 19.

Adenosine Diphosphate↗
PubMed1981

Micellar solubilization of biopolymers in organic solvents. Activity and conformation of lysozyme in isooctane reverse micelles.

Lysozyme solubilized in reverse micelles of bis(2-ethylhexyl) sodium sulfosuccinate in isooctane containing as little as 0.8% water (v/v) has been shown to be active. The amount of enzymatic activity depends on the water content and the pH of the reverse micellar system and under optimum conditions (i.e. pH 7.7 with 1.2% water) is 90% of the activity in water. The dependence of lysozyme activity on pH in reverse micelles is different than that in water, with the entire pH profile shifted 2 to 3 pH units higher in reverse micelles. Moreover, maximum enzyme activity is not found at the highest water contents tested (i.e. 1.6% and 2.0% water), but instead at 1.2% water. The Km for the N-acetylglucosamine oligomers used as substrate is 0.1 mM in reverse micelles (compared to 0.01 mM in water) when the concentration of substrate is referred to the water pools. Spectroscopic studies (CD, fluorescence, and UV absorbance) indicate that the conformation of lysozyme is significantly different in reverse micelles compared to water. In particular, CD studies indicate that the helical content of lysozyme changes from approximately 34% in water to approximately 48% in reverse micelles. Conformation and activity data are qualitatively correlated to the anomalous character of water in the reverse micelles. In particular, this may induce a stronger hydrogen bonding within the lysozyme which would in turn increase both the pKa of certain amino acid residues and the helical content of the macromolecule.

Animals↗
PubMed1994

Study of access recirculation in reversed temporary indwelling catheters.

At the Ottawa Civic Hospital hemodialysis unit, our prescribed blood flow rate for temporary indwelling catheters runs at 200 mls/min. We were concerned that, with the reversal of the ports of these catheters, our patients were not receiving the dialysis prescription ordered for them due to decreased efficiency of their treatment. Twenty-five of 108 patients in the program were included in a study related to the percentage of access recirculation when ports were reversed or not reversed. Of those 25 patients, approximately 42% had their ports reversed. The study took place over a two-week period and involved approximately six dialysis sessions per patient. Results indicated that the percentage recirculation increased from 2.3%-4.1% when ports were connected normally, to 12% when ports were reversed. As a result, a policy is now in place whereby our patients' treatment time is increased 20 minutes for reversed ports. In summary, recirculation rate increased with reversal of ports in temporary indwelling catheters. Extension of prescribed treatment times when ports are reversed will maintain the efficiency of dialysis.

Adult↗
PubMed1993

Doppler ultrasonography after renal transplantation: value of reversed diastolic flow in diagnosing renal vein obstruction.

The observation of reversed diastolic flow during Doppler ultrasonography (US) of renal transplants has been described as sensitive but not specific in the diagnosis of renal vein thrombosis. To determine the diagnostic accuracy of reversed diastolic flow for renal vein obstruction in patients who underwent renal transplantation at a tertiary-care teaching hospital over a 3-year period, the authors identified all patients in whom reversed diastolic flow was observed during Doppler US (17 patients) and those in whom complete renal vein obstruction occurred, necessitating nephrectomy (16 patients). Three types of reversed diastolic flow were found; the wave-forms of two of these had a large reversed component. One of these two types was present in nine of the patients in whom complete venous obstruction occurred. The sensitivity, specificity and positive predictive value of reversed diastolic flow were 82%, 99% and 75% respectively. The authors conclude that a US finding of reversed diastolic flow with a large reversed component is a sensitive and specific sign of renal vein obstruction, usually renal vein thrombosis.

Diastole↗
PubMed1977

[Reversal of intestinal segments for therapy of malabsorption after small bowel resection. Experiments on animals (author's transl)].

Following massive small bowel resection malnutrition occurs as a result of impaired digestion and malabsorption. Of the numerous methods of operation suggested to improve intestinal absorption only the reversal of intestinal segments seems to be promising. Since so far this method was used clinically only in single cases, the method was studied experimentally in 50 minipigs (divided in 4 groups: 90 p.c.-small bowel resection without reversal, with primary or secondary reversal, and normal controls). The reversed segments 5 or 10 cm in length were inserted in the middle or at the end of the remaining jejunum or ileum. In comparison with the animals without intestinal reversal the animals with reversed segments showed a significant increase of intestinal transit time and of absorptive capacity, a nearly normal weight development and a considerably better adaptation of the remaining small bowel. In contrast to that the animals without reversal showed after an average of 3 months extreme cachexia. These encouraging experimental results with reversed segments in short bowel syndrome justifies in our opinion the application of this therapeutic principle in humans.

Animals↗
PubMed1996

Preoperative reverse transcriptase polymerase chain reaction for prostate specific antigen predicts treatment failure following radical prostatectomy.

PURPOSE: We previously demonstrated than an enhanced reverse transcriptase-polymerase chain reaction assay for prostate specific antigen (PSA) can predict final pathological stage in radical prostatectomy patients. The potential role of the assay in predicting serum PSA recurrence after radical prostatectomy was explored. MATERIALS AND METHODS: We evaluated 100 radical prostatectomy candidates by reverse transcriptase polymerase chain reaction preoperatively, and status was compared to serum PSA, Gleason score and final pathological results. Potential surgical failure was defined as tumor at the surgical margin or extending into the seminal vesicle. Patients were monitored postoperatively by serum PSA every 4 months. Kaplan-Meier analysis was used to evaluate the correlation between reverse transcriptase polymerase chain reaction and disease recurrence, defined as a PSA of 0.2 ng/ml. or greater. RESULTS: Enhanced reverse transcriptase polymerase chain reaction for PSA had a stronger correlation with potential surgical failure than preoperative serum PSA or Gleason score (relative risks 15.2, 5.9 and 3.2, respectively). The correlation between these modalities and PSA recurrence was evaluated during a mean followup of 13.6 months (range 5 to 26). Of 36 patients with positive reverse transcriptase polymerase chain reactions 9 had failure by PSA compared to 3 of 64 (4.7%) with negative polymerase chain reactions (p<0.0286). The relative risk for failure by reverse transcriptase polymerase chain reaction was 3.6. Gleason score and serum PSA had higher correlations with postoperative PSA elevations (relative risk 13.2 and 7.6, respectively). A Cox regression analysis model demonstrated that reverse transcriptase polymerase chain reaction for PSA can be used in conjunction with Gleason score and provides statistically significant risk information. CONCLUSIONS: Enhanced reverse transcriptase polymerase chain reaction for PSA is a statistically significant predictor of potential failure by pathological analysis and of disease recurrence by PSA. Longer followup data are required to define further the role of the assay in the management of patients with prostate cancer.

Aged↗
PubMed1996

Speech perception of temporally reversed syllables by normally hearing adults.

BACKGROUND: The general purpose of this study was to determine the effects of phonological knowledge on performance on a simple task of speech discrimination. If a test can be devised that is independent of the subject's phonological knowledge then it should be possible to measure auditory speech perception capacity in young deaf children before they have developed spoken language skills. In the present study, temporal reversal was used to limit normal subjects' use of phonological knowledge without removing acoustic information. METHODS: An auditory, 3-interval, forced-choice (oddity) test of phonetic contrast perception was administered to 5 normally hearing adult speakers of English. Perception of place of articulation was measured in stops and fricatives--both voiced and unvoiced. The test was presented both with natural syllables and with the same syllables reversed in time. In addition, the test was administered with a fixed context and a mixed context (i.e., context changing from trial to trial). The subject's task was always to identify the odd-man-out in each presentation of 3 syllables. RESULTS: Overall, error rate was significantly higher for temporally-reversed than for natural syllables (6.7% versus 1.7%). The effect was, however, present only in stops (11.7% versus 1.7%) and not in fricatives (0.8% versus 0.8%). Changing from a fixed to a mixed context did not influence the effect of reversal. There were, however, significant differences among subjects in the temporally-reversed condition. CONCLUSIONS: The main effect of reversal supports the hypothesis that performance falls, even on a simple task, when phonetic processing is impeded. The fact that the effect is present only for stops adds further support, because temporal reversal does not affect the essential acoustic properties of fricatives. The presence of inter-subject differences suggests that the ability to switch to an acoustic strategy when phonetic processing is impeded may be affected by aptitude and experience. The fact that error rate was low, even for reversed stops, suggests that a test of this type could be used for assessing speech perception capacity in deaf children with impaired phonology. The procedure is not, however, completely independent of the effects of phonetic processing.

Adult↗
PubMed1996

Thallium-201 reverse redistribution at reinjection imaging correlated with coronary lesion, wall motion abnormality and tissue viability.

UNLABELLED: Previous studies based on standard stress-redistribution 201TI scintigraphy provided conflicting results about the clinical significance 201Tl reverse redistribution. Recent observations indicate that the majority of these defects normalize following reinjection reflecting viable myocardium. METHODS: In this study, the meaning of reverse redistribution occurring at reinjection imaging, its relation to standard 4-hr redistribution, coronary lesion, abnormal wall motion and tissue viability were assessed. A region with normal activity in the stress image was considered as having reverse redistribution if 201Tl activity at reinjection imaging was definitely abnormal with a decrease in relative tracer uptake >15% of the peak. From a series of 270 patients, 29 showed reverse redistribution. Of these 29 patients, 27 had evidence of previous myocardial infarction. Coronary lesions were detected in all but 1 patient. Average ejection fraction was 0.38 +/- 0.11. RESULTS: On a segmental basis, 50/377 regions showed the pattern of reverse redistribution. A significant coronary lesion (> or = 50%) was found in 78% of these regions; occlusion rate was 50%, and collateral circulation was found in 35% of occluded vessels. Hypokinesis or akinesis was present in 72% of segments. Tissue viability, defined as an uptake >55% of the peak, was found in 44% of these segments. The 50 segments showing reverse redistribution were divided into two groups according to an abnormal uptake also at 4-hr redistribution (group 1, 25 segments) or appearing only following reinjection (group 2,25 segments). Despite segments of group 1 showing a higher degree of coronary stenosis (80 +/- 32 versus 59 +/- 43%, p < 0.01), a similar rate of coronary occlusion, ventricular dysfunction and maintained viability was found in the two groups. CONCLUSION: Reverse redistribution in chronic coronary artery disease is frequently associated with significant coronary lesion, collateral-dependent dysfunctioning myocardium and preserved tissue viability. The occurrence of reverse redistribution following reinjection expands the indication for viability imaging to all patients with known coronary artery disease and regional wall motion abnormalities who undergo diagnostic and prognostic 201TI scintigraphy.

Coronary Angiography↗
PubMed1997

The feasibility of cryopreservation of sperm harvested intraoperatively during vasectomy reversals.

PURPOSE: Intracytoplasmic sperm injection during in vitro fertilization involves the microinjection of a single sperm into each egg from the partner. Pregnancies have resulted from this powerful new technology when fewer than 100 motile sperm were present in the semen, or when sperm were obtained from the epididymis or testicle by open operations or needle aspirations. Some surgeons have cryopreserved sperm obtained from the vas or epididymis during vasectomy reversals. However, cryopreservation of nonmotile sperm serves no useful purpose. MATERIALS AND METHODS: We performed a retrospective analysis of 603 vasectomy reversals in which the intraoperative vasal and/or epididymal fluid was examined microscopically. The motility of the sperm obtained intraoperatively was used as a gauge for the potential use of such sperm for in vitro fertilization and intracytoplasmic sperm injection after cryopreservation and thawing, should the vasectomy reversal fail. RESULTS: Motile sperm were present in the intraoperative vasal or epididymal fluid in 35% of all vasectomy reversals (34% of first and 39% of repeat procedures). The percentage of reversals in which motile sperm were present in the intraoperative fluid was not related to the time from vasectomy until reversal. CONCLUSIONS: The absence of motile sperm in the intraoperative vasal or epididymal fluid precludes consideration of sperm cryopreservation during vasectomy reversals. Although to our knowledge the minimum percentage of sperm motility needed for in vitro fertilization and intracytoplasmic sperm injection after cryopreservation and thawing has not been established, our results provide surgeons with information to judge the merit of sperm harvesting and cryopreservation during vasectomy reversals.

Cryopreservation↗
PubMed1993

HIV-1 reverse transcriptase: inhibition by 2',5'-oligoadenylates.

2',5'-Oligoadenylates (2-5A) and derivatives are noncompetitive inhibitors of primer/HIV-1 reverse transcriptase complex formation. The mechanism and specificity of this inhibitory action of 2-5A and 2-5A derivatives have been evaluated with 2-5A molecules modified in ribosyl moiety, chain length, extent of 5'-phosphorylation, and 2',5'-phosphodiester linkage. UV covalent cross-linking of preformed complexes of p66/p66 homodimer or p66/p51 heterodimer recombinant HIV-1 reverse transcriptase and the primer analog pd(T)16 allowed analysis of the initial step in HIV-1 reverse transcriptase-catalyzed DNA synthesis. Utilizing this primer binding assay, it is demonstrated that 2-5A and 2-5A derivatives inhibit the binding of pd(T)16 to HIV-1 reverse transcriptase. This inhibition is specific for the 2',5'-internucleotide linkage in that the corresponding 3',5'-adenylate derivatives do not exhibit inhibitory activity. Enhanced inhibitory properties were observed following modifications of the 2-5A molecule which result in an increase in hydrophobicity. Replacement of the D-ribosyl moiety of 2-5A with the 3'-deoxyribosyl moiety increased the inhibition of primer/HIV-1 reverse transcriptase complex formation 15-20%. 2',5'-Phosphorothioate substitution yielded the most effective inhibitors, with Ki's of 7-13 microM. In all cases, inhibition of primer/HIV-1 reverse transcriptase complex formation showed a preference for the 5'-triphosphate moiety. Nonphosphorylated derivatives were not inhibitory; 5'-monophosphate derivatives exhibited little or no inhibition. The inhibition of primer binding to HIV-1 reverse transcriptase correlated well with the inhibition of DNA-directed DNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenine Nucleotides↗
PubMed2005

Analysis of interactions of DNA polymerase beta and reverse transcriptases of human immunodeficiency and mouse leukemia viruses with dNTP analogs containing a modified sugar residue.

Substrate properties of various morpholinonucleoside triphosphates in the reaction of DNA elongation catalyzed by DNA polymerase beta, reverse transcriptase of human immunodeficiency virus (HIV-1 RT), and reverse transcriptase of Moloney murine leukemia virus (M-MuLV RT) were compared. Morpholinonucleoside triphosphates were utilized by DNA polymerase beta and HIV-1 reverse transcriptase as substrates, which terminated further synthesis of DNA, but were virtually not utilized by M-MuLV reverse transcriptase. The kinetic parameters of morpholinoderivatives of cytosine (MorC) and uridine (MorU) were determined in the reaction of primer elongation catalyzed by DNA polymerase beta and HIV-1 reverse transcriptase. MorC was a more effective substrate of HIV-1 reverse transcriptase and significantly less effective substrate of DNA polymerase beta than MorU. The possible use of morpholinonucleoside triphosphates as selective inhibitors of HIV-1 reverse transcriptase is discussed.

Catalysis↗