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Polydioxanone in coronary vascular surgery.

We have used polydioxanone (PDS) in 50 patients who underwent coronary artery bypass grafting. The anastomoses consisted of suturing an autologous vein graft to the coronary artery (122 operations), a vein graft to the aorta (63 operations) and the internal mammary artery to the coronary artery (33 operations). The recipient coronary artery was subjected to endarterectomy in 28 instances. The anastomoses proved to be reliable in the early postsurgical period; no bleeding was attributed to the PDS suture. Clinical follow-up for a maximum of two-and-half years, completed using control coronary angiograms in selected cases, demonstrated good results. The practical properties of PDS were evaluated to be at least as good as those of polypropylene. Experiments have clearly shown that small artery anastomoses heal more favourably after the use of absorbable sutures than after the use of nonabsorbable sutures. Because of this finding and on the basis of our clinical experience, we believe the application of PDS in coronary surgery should be recommended as an alternative treatment.

Adult↗

The impact of paired motor unit discharges on tremor.

We studied paired discharges (PDs) of single motor units (MUs) of the first dorsal interosseus muscle in parkinsonian and essential tremor. The number of PDs increased with increasing tremor strength and the duration of their intervals shortened. The amplitudes of the single tremor beats showed a significant negative correlation to the duration of the intervals of the preceding PDs. It is concluded that PDs play an important role as tremor amplifiers. The basic mechanism is probably the more than linear summation of two twitch contractions with short interval which is known from animal experiments.

Adult↗

[Responses of neurons of an isolated cortical strip in a state of convulsive excitation to single electrical stimuli].

Responses of isolated cortical slab neurons to single stimuli before, during and after the development of epileptiform state in a slab were investigated in experiments on immobilized and locally anaesthetized cats. It was shown that during the development of generalized seizure activity in an isolated cortical slab its neurons generate EPSP and paroxysmal depolarizing shifts (PDS) of the membrane potential (MP) accompanied by refractory periods. Refractory periods coincide with PDS plato and MP repolarizing shifts. During these shifts single electrical stimuli produce gradually transforming PDS. After cessation of the ictal activity neurons are still able to generate PDS to single stimuli for some time. It is suggested that the role of postsynaptic responses in genesis of the epileptiform activity is not the most important. Nonsynaptic factors are, probably, involved in its generation.

Animals↗

Sustained release tablets based on chitosan and carboxymethylcellulose sodium.

Chitosan and mixtures of chitosan with carboxymethylcellulose sodium (CMC-Na) were examined as vehicles for sustained release tablets of water-insoluble drugs. Prednisolone (PDS) was selected as a model of a water-insoluble drug for this study. Sustained release of PDS from tablets prepared by direct compression of chitosan and CMC-Na was demonstrated in model JP X fluids. Furthermore, the release rate of PDS could be controlled by changing the relative amounts of chitosan and CMC-Na, or the amount of PDS in the tablets, and by certain extra additives. Such chitosan/CMC-Na mixtures are a promising basis in the design of sustained release dosage forms of water-insoluble drugs.

Carboxymethylcellulose Sodium↗

Comparison between absorbable and nonabsorbable, monofilament sutures for end-to-end arterial anastomoses in growing pigs.

End-to-end anastomoses of the iliac arteries in growing pigs were constructed with interrupted 7-0 absorbable polydioxanone (PDS) or polypropylene (Prolene) sutures. Comparison between the two monofilament suture materials was made with respect to macroscopic and microscopic examinations, angiographic findings, recorded tensile breaking forces, and calculated blood flow values within the arterial walls at the level of the anastomoses. The angiographic examinations and the recorded tensile breaking forces did not reveal any difference between PDS- and Prolene-sutured anastomoses. On the other hand, the macroscopic findings, the histologic examination, and the calculated blood flow values (6.1 +/- 4.7 and 16.8 +/- 2.3 ml/min/100 gm for PDS- and Prolene-sutured anastomoses, respectively) point to a far more pronounced inflammatory tissue reaction with Prolene. The obtained differences clearly suggest the use of absorbable PDS instead of nonabsorbable Prolene sutures for arterial anastomoses.

Animals↗

Proteoglycans of rabbit corneal stroma. Isolation and partial characterization.

Proteoglycans extracted from rabbit corneal stroma can be separated by ion exchange and gel chromatography into two proteokeratan sulfates (PKS-I, PKS-II) and two proteodermatan sulfates (PDS-I, PDS-II). PKS-I (21% of the total glycosaminoglycans) contains 48% protein, and PKS-II (43% of the total) has 57% protein. In both, the only hexosamine is glucosamine, 7% of which is found in oligosaccharides. There is much more sialic acid in the oligosaccharides of PKS-II than of PKS-I, and the amino acid compositions of the two proteoglycans differ significantly. The keratan sulfates isolated from them by papain digestion are different in size, but both are digested by endo-beta-galactosidase. PDS-I (30% of the total glycosaminoglycans) has 32% protein, and 35% of its uronic acid is iduronic acid. PDS-II (6% of the total) has 42% of its uronic acid as iduronic. In general, the four rabbit proteoglycans resembled those of human and bovine corneal stroma in being smaller and more protein-rich than those of cartilage.

Amino Acids↗

Protective effects of panaxadiol saponins on cardiac functions in burned rats.

AIM: To study the effects of panaxadiol saponins (PDS) on burn rat heart functions and try to find its mechanisms. METHODS: A 35% skin-full-thickness burn was produced by using napalm in Wistar rats. PDS 30 mg kg-1 was injected i.p. to rats immediately after burn and repeated 2 h before examination. Using the isolated perfused working heart and biochemistry methods, heart rate (HR), cardiac output (CO), coronary flow (CF), left ventricular pressure (LVP), aortic pressure (AP), +/- dp/dtmax, and content of malondialdehyde (MDA), activity of superoxide dismutase (SOD) in ventricular myocardium homogenate were examined 8 h after burn. RESULTS: After burn, HR, CO, CF, LVP, AP, +dp/dtmax, -dp/dtmax, and SOD activity decreased from 206 bpm, 92 mL min-1 g-1, 26 mL min-1 g-1, 7 kPa, 5.9 kPa, 149 kPa s-1, 73 kPa s-1, 2.9 NU/mg protein to 162 bpm, 72 mL min-1 g-1, 14 mL min-1 g-1, 4 kPa, 2.2 kPa, 77 kPa s-1, 44 kPa s-1, 1.7 NU/mg protein, respectively, and MDA content raised from 0.77 nmol/mg protein to 1.35 nmol/mg protein (P all < 0.05). But in PDS-treated group, above decreased or increased dates restored to 202 bpm, 91 mL min-1 g-1, 25 mL min-1 g-1, 6 kPa, 4.1 kPa, 112 kPa s-1, 62 kPa s-1, 2.8 NU/mg protein, 0.91 nmol/mg protein, respectively (P all < 0.05 vs burn). CONCLUSION: PDS exerts definite protective effects on the cardiac functions after burn injury possibly through its enhancement of SOD activity and the reduction of both the levels of free radicals and lipid peroxides (LPO) of the myocardium.

Animals↗

A biocompatibility study on peritoneal dialysis solution bags for CAPD.

Numerous factors related to the composition of peritoneal dialysis solutions (PDS) contribute to the pathogenesis of peritoneal fibrosis during continuous ambulatory peritoneal dialysis (CAPD). They include high osmolarity, low pH, and the presence of lactate, which may be responsible for stimulating the proliferation of peritoneal fibroblasts (PF) and for the toxicity on the peritoneal mesothelial cells (PMC). Similar effects could be hypothesized for the plasticizers released from the PDS bags, usually made of polyvinyl chloride (PVC), such as the acid esters of phthalic acid, particularly bis-(2-ethylhexyl) phthalate (BEHP). Recently, however, new BEHP-free bags (Clear-Flex, Bieffe, Italy) made of three layers (polyethylene, nylon, and polypropylene) have been introduced. The aim of this work is to evaluate in vitro the effects of samples of PDS contained in PVC bags (Bieffe) and in Clear-Flex bags on the proliferative capacity of peritoneal fibroblasts and peritoneal mesothelial cells, and the release of interferon gamma (IFN gamma), interleukin-1 (IL-1) and prostaglandin E2 (PGE2) from peritoneal T lymphocytes (PTLs) and macrophages (PM phi s). Results have shown that in the presence of PDS samples contained in PVC bags, the proliferative capacity of peritoneal fibroblasts was higher than in Clear-Flexbags. There was also an increased release of IFN-gamma and IL-1 from PTLs and PM phi s (cytokines that stimulate the collagen synthesis) and a decreased release of PGE2 (cytokines which inhibit the collagen synthesis). An inhibiting action on peritoneal mesothelial cells was also seen.(ABSTRACT TRUNCATED AT 250 WORDS)

Biocompatible Materials↗

Low- and high-turnover bone disease in continuous ambulatory peritoneal dialysis: effects of low-Ca2+ peritoneal dialysis solution.

Calcium carbonate (CaCO3) is an effective phosphate (PO4) binder in uremics, and its use reduces aluminum (Al) intake. By maintaining high serum Ca2+, it decreases serum parathyroid hormone (PTH) levels. Hypercalcemia, however, often limits the dosage. In order to evaluate the effects of a low-Ca peritoneal dialysis solution (PDS) (1.25 mmol/L) on Ca metabolism, we studied the following in 12 continuous ambulatory peritoneal dialysis (CAPD) patients with hypercalcemia (6 with low PTH levels, low-turnover bone disease, group 1, and 6 with high PTH levels, high-turnover bone disease, group 2, documented by bone biopsies): serum Ca2+; serum PTH; bone morphology. The follow-up was 12 months. Results show that in both groups within the third month there was a decrease in serum Ca2+. In group 1 serum PTH increased, reaching the norm, and in group 2 it further increased exceeding the norm. Because in both groups serum Ca2+ was normal, it was possible to increase oral CaCO3 (10.5 +/- 2.5 g/day) to control PO4 levels and to stop Al gels. In group 2, in order to avoid the further rise of serum PTH, the low-Ca PDS was supplemented with 2 micrograms/day of 1,25(OH)2D3 (vitamin D3); this was followed by a reduction in serum PTH with no increase in Ca2+ and PO4. The use of low-Ca PDS may be useful in preventing hypercalcemia in CAPD patients treated with high oral doses of CaCO3 and in improving low-turnover bone disease, while low-Ca PDS supplemented with vitamin D3 improves high-turnover bone disease.

Administration, Oral↗

A statistical approach to the quantitative comparison of pulsatile flow in vitro data of prosthetic heart valve testing.

BACKGROUND AND AIMS OF THE STUDY: In vitro evaluation and animal testing are fundamental steps in the assessment of prosthetic heart valves before their use in clinical practice. Valve testing under pulsatile conditions is the best in vitro simulation of cardiac valve function, and the ensuing results should support the surgeon's decision concerning the time of valve replacement. However, limits in hydraulic reproduction of cardiac function and differences in protocol implementation of in vitro testing lead to difficulties in obtaining reliable and comparable results. Debate among researchers and standardizing bodies about discrepancies in results becomes critical in light of the European CE certification of implantable medical devices. An interlaboratory environment has been created at the Biomedical Engineering unit of the Istituto Superiore di Sanita in Rome, which uses differing test apparatus to evaluate prosthetic heart valves in vitro, in order to define significant measurement parameters and procedures that produce comparative data. METHODS: Two prosthetic valves-a tilting disc and a bileaflet valve-each sized 29 mm, were tested in the aortic position on two different pulse duplicators (PDs), namely the Dynatek MP1 and a system developed at the University of Sheffield. The common protocol adopted was the FDA Interlaboratory Comparison Testing Protocol. Original software was used to manage all test phases, thus minimizing operator-dependent variability in both systems and imposing strict control of experimental conditions. Statistical analysis performed on the data followed two approaches: (i) separate fitting of the two regression equations of pressure drop-flow rate relationship obtained for each valve on both PDs, and (ii) application of a multiple regression model, to fit a single regression equation of pressure drop-flow rate relationship, using data obtained from both PDs for each valve. In addition, an additional independent (dummy) variable was introduced. RESULTS AND CONCLUSIONS: Using this approach, the valve parameter range was obtained and, by imposing strict control of the experimental set-up, the coincidence of the two valve power laws, estimated by each of the two PDs, was studied.

Heart Valve Prosthesis↗

Efficient CRISPR/Cas9-mediated genome editing of phytoene desaturase in Musa-AAA: a critical step for genetic improvement of east African highland bananas.

East African highland bananas (EAHBs), locally referred to as "matooke", are an important staple crop in Uganda. The EAHBs have a triploid genome (AAA) with a large phenotypic diversity in the Great Lakes region of Africa and are challenged by both abiotic and biotic factors. The EAHBs have been improved through conventional breeding and genetic engineering though facing challenges such as genetic drag of unfavorable traits and complex regulatory processes, respectively. Therefore, a more precise approach for crop improvement such as genome editing is highly recommended. In the current study, we assessed the feasibility and applicability of the CRISPR/Cas9 mediated-genome editing in EAHBs. Two sgRNAs were designed from the Nakitembe phytoene desaturase (PDS) gene and used to edit the PDS gene in Nakitembe (NKT) and NAROBan5 (M30) cultivars. A total of 47 NKT and 130 M30 events were regenerated via agrobacterium-mediated transformation of banana embryogenic cell suspensions. Up to 100% and 94.6% albinism rates were observed in Nakitembe and M30 cultivars respectively with additional albino-variegated and variegated phenotypes observed in M30 only. Carotenoid analysis revealed a significant reduction of total carotenoid content in edited events with all complete albinos showing no detectable carotenoids implying that the carotenoid biosynthetic pathway was effectively disrupted. Sequence analysis revealed that all of the edited events had frameshift mutations leading to PDS disruption. Overall, this study presents the first report of CRISPR/Cas9 genome editing in EAHBs and more interestingly on a hybrid, M30 showing high precision and efficiency. This validated genome editing system provides a robust platform for targeted EAHB improvement.

CRISPR/Cas9↗

Parenting behaviors associated with risk for offspring personality disorder during adulthood.

CONTEXT: Research has suggested that some types of parental child-rearing behavior may be associated with risk for offspring personality disorder (PD), but the association of parenting with offspring PD has not been investigated comprehensively with prospective longitudinal data. OBJECTIVE: To investigate the association of parental child-rearing behavior with risk for offspring PD during adulthood. DESIGN: The Children in the Community study, a prospective longitudinal investigation. SETTING AND PARTICIPANTS: A community-based sample of 593 families interviewed during childhood (mean age, 6 years), adolescence (mean ages, 14 and 16 years), emerging adulthood (mean age, 22 years), and adulthood (mean age, 33 years) of the offspring. MAIN OUTCOME MEASURE: The Structured Clinical Interview for DSM-IV Personality Disorders. RESULTS: Ten types of parenting behavior that were evident during the child-rearing years were associated with elevated offspring risk for PD during adulthood when childhood behavioral or emotional problems and parental psychiatric disorders were controlled statistically. Parental behavior in the home during the child-rearing years was associated with elevated risk for offspring PD at mean ages of 22 and 33 years. Risk for offspring PD at both assessments increased steadily as a function of the number of problematic parenting behaviors that were evident. Low parental affection or nurturing was associated with elevated risk for offspring antisocial (P = .003), avoidant (P = .01), borderline (P = .002), depressive (P = .02), paranoid (P = .002), schizoid (P = .046), and schizotypal (P<.001) PDs. Aversive parental behavior (eg, harsh punishment) was associated with elevated risk for offspring borderline (P = .001), paranoid (P = .004), passive-aggressive (P = .046), and schizotypal (P = .02) PDs. CONCLUSIONS: Parental behavior during the child-rearing years may be associated with risk for offspring PD that endures into adulthood. This risk may not be attributable to offspring behavioral and emotional problems or parental psychiatric disorder, and it may not diminish over time. Low parental nurturing and aversive parental behavior during child rearing may both be associated with elevated risk for offspring PDs.

Adolescent↗

Establishing the psychometric properties of the DSM-III-R personality disorders: implications for DSM-V.

In this study, symptom (item) level data were used to perform a psychometric analysis of the DSM-III-R personality disorders (PDs). Determined for each PD criteria set were convergent validity, discriminant validity, and internal consistency. The results indicated that the majority of the PD criteria sets (6 of the 11 ) possessed adequate convergent validity, although discriminant validity was problematic for most of these disorders. Internal consistency was also weak for the PD criteria sets, with only 3 of the 11 exceeding a minimum cutoff score of .70. The present study employed a methodology modeled after the one reported by Morey (1988a), and the results of the two studies were highly similar. Consistent findings across the two data sets can be taken to reflect the actual psychometric properties of the DSM-III-R PDs. The success of our replication demonstrates the potential that large-scale psychometric investigations hold for aiding the development and refinement of the DSM PDs.

Humans↗

Blastic transformation in essential thrombocythemia. In vitro differentiation of blast cells into granulocytic, erythroid, and megakaryocytic lineages.

A 57-year-old man with essential thrombocythemia (ET) developed myelofibrosis, that progressed to a blastic transformation state. The characteristics of the blastic cells were serially studied both morphologically and phenotypically as well as in cell culture. The blastic cells that were first detected in peripheral blood had features of myeloid stem cells with slight differentiation toward megakaryocytic lineage. However, later in the course, most of the blastic cells were immature. During culture in the presence of human plasma-derived serum (PDS), some blastic cells obtained at the initial stage differentiated, mainly to both granulocytes and macrophages morphologically, but later tended to differentiate into both megakaryocytes and macrophages. Finally the blasts appeared to have lost their ability to differentiate morphologically. However, the blasts formed mixed colonies consisting of erythroblasts, granulocytes, macrophages, and immature blasts when cultured in methylcellulose with PHA-leukocyte conditioned medium. In addition, the blastic cells in suspension culture strongly expressed phenotypic features which are characteristic of erythroblasts, in the presence of both PDS and 12-0-tetradecanoylphorbol 13-acetate (TPA), whereas they expressed features of megakaryoblasts in the presence of PDS alone. These results suggest that essential thrombocythemia is of myeloid stem cell origin. This is the first case in the literature in which a clonal evolution in ET has been followed closely, essential events were identified serially, and the blastic cells, which appeared as a result of the progression of ET, were found to have the capability to differentiate toward the three myeloid lineages.

Blast Crisis↗

Reinforced poly(L-lactic acid) fibres as suture material.

In this study, reinforced poly(L-lactic acid) (PLLA) fibers made by a dry-spinning/hot-drawing process were evaluated for use as a suture. The initial tensile strength of the PLLA fibers was lower than the initial tensile strength of the commercially available sutures: PDS, Vicryl, silk, and Ethilon. However, after 12 weeks immersion in a phosphate saline buffer at 37 degrees C, PDS sutures have lower tensile strength than PLLA sutures and the tensile strength of Vicryl was unmeasurable because of fragmentation. Initially, PLLA fibers disintegrated into fibrils during degradation triggering an inflammatory response comparable to degradable multifilament sutures. However, the intensity of the inflammatory response against the PLLA fibers decreased and after 80 weeks implantation in the muscle layer of the abdominal wall of rats it was comparable to the one against Ethilon. The inflammatory response against Ethilon, which is considered to be nondegradable, increased in the same period, probably due to the change in shape. In practice, the handling characteristics of PLLA sutures are superior to the monofilament sutures like PDS and Ethilon and comparable with the multifilament sutures like Vicryl and silk. The knot security of PLLA sutures are expected to be better than the knot security of the monofilament sutures, but this remains to be investigated. It is concluded that dry-spun/hot-drawn (reinforced) PLLA fibers have the potential for use as long-term degradable suture material.

Animals↗

Biological response to a new composite polymer augmentation device used for cruciate ligament reconstruction.

A resorbable composite augmentation cord braided of poly(L-lactide) and poly(L-lactide-co-glycolide) fibers was designed for the temporary protection of repaired cruciate ligaments. This study examined the biocompatibility of the new device and the influence of augmentation duration on ligament healing in a sheep model. The anterior cruciate ligament (ACL) was cut close to the femoral insertion and reinserted with sutures. The repaired ACLs were augmented with the slowly degrading new composite cord and alternatively with a faster degrading polydioxanone cord (PDS). A tendon graft group (gold standard) served as control. Histological evaluation and biomechanical testing were performed after 6 months. The composite cord showed no signs of degradation, whereas the PDS was intra-articularly resorbed. Both devices showed only minor foreign body reactions, proving their good biocompatibility. However, 9 of 11 composite cords had ruptured too early because of fatigue at the bone tunnel entrances. All operated knees were less stable than the nonoperated collateral joints. Knees equipped with the composite cord showed the largest anterior instabilities, whereas the PDS-augmented group exhibited in some cases knee instabilities comparable with that of the tendon group. A positive effect of a longer mechanical protection by a slowly degrading augmentation could not yet be shown. The fatigue strength of the device still needs improvement.

Animals↗

Proliferative characteristics of clonal endothelial cell strains.

We have utilized clonal strains of bovine fetal aortic endothelial cells to study cellular senescence in a differentiated cell type of physiological significance. Serial subcultivation of nine endothelial clones derived from three fetal calf aortas revealed proliferative life-spans in vitro of 53--125 population doublings (PDs), compared with 60 and 143 PDs for two lines of bovine fetal lung cells and 85 and 147 PDs for two lines of bovine vascular smooth muscle cells. Serial growth curves showed marked reductions associated with endothelial cellular senescence both in cellular growth rate and culture plateau density. Studies of the 24-hour [3H]-thymidine labeling index versus percentage of proliferative life-span completed indicated that clonal endothelial cultures contained a large proportion (greater than 90%) of rapidly cycling cells until about 75% of the lifespans were completed. Senescent endothelial cells showed evidence of large increases in cell area, cell volume, and protein content. In those clones examined, one specialized endothelial function, Factor VIII antigen expression, was retained qualitatively throughout the life-spans.

Animals↗

Human platelet alpha granules contain a nonspecific inhibitor of megakaryocyte colony formation: its relationship to type beta transforming growth factor (TGF-beta).

Whole blood serum (WBS) and platelet-poor plasma-derived serum (PDS) from the same normal subject were compared for their abilities to support human megakaryocyte (MK) colony formation. In all cases, PDS promoted the growth of a higher number (20-50%) of MK colonies than did WBS. Increasing amounts of WBS decreased the number of colonies, whereas increasing concentration of PDS had no marked effects. Crude platelet extracts or platelet secretory products from thrombin-activated platelets also elicited an inhibition of MK colony formation in a dose-dependent manner. A complete inhibition was found for a dose equivalent to 1.10(9) platelets/ml and a 50% inhibition in a range of 1.10(7)-1.10(8) platelets/ml. These platelet products were also inhibitory for erythroid progenitor growth. Platelets from two patients with gray platelet syndrome elicited only a minor inhibition of MK growth, suggesting that the platelet alpha granule is the origin of this inhibition. When platelet extracts were acid-treated, the biological activity of the inhibitor on CFU-MK and CFU-E growth was 20-50-fold higher. In addition, a potent stimulatory activity on the growth of day 7 CFU-GM was observed. The enhancement of biological activities by acid treatment suggests that type beta transforming growth factor (TGF-beta) could be involved in this platelet inhibitory activity. The homogeneous native TGF-beta (from 1 pg to 1 ng/ml) produced the same effects previously induced by platelet products. It totally inhibited CFU-MK growth (at a 500 pg/ml), it inhibited CFU-E growth, and it stimulated growth of day 7 CFU-GM in the presence of a colony-stimulating factor. The inhibition of CFU-MK growth was also observed on purified progenitors. In conclusion, these results suggest that TGF-beta may be implicated in negative autocrine regulation of megakaryopoiesis. However, since this molecule has ubiquitous biological activities, its physiologic relevance as a normal regulator of megakaryopoiesis requires further investigation.

Blood Physiological Phenomena↗