Collagen synthesis and heart failure

Little is known about collagen metabolism in heart failure, with or without left ventricular systolic dysfunction. We studied serum concentrations of the carboxy-terminal propeptide of procollagen type I (PIP), a marker of collagen type-I synthesis, and of the carboxy-terminal telopeptide of collagen type I (ICTP), a marker of collagen type-I degradation, in 70 patients admitted for heart failure (35 with depressed left ventricular systolic function and 35 with preserved left ventricular systolic function) and in 30 control subjects. Patients with kidney failure, liver disease, metabolic bone disease, rheumatic disease, recent (within 3 months) major trauma or surgery, or serious wounds were excluded. The concentration of the collagen synthesis marker, PIP, was higher in heart failure patients than control subjects, at 140+/-56.38 mg/L vs 113.66+/-36.6 microg/L, respectively (P=.01). However, there was no difference in the concentration of the collagen degradation marker, ICTP, between heart failure patients and control subjects, at 2.89+/-2.37 mg/L vs 2.26+/-1.7 microg/l, respectively. In heart failure patients, left ventricular systolic function had nonsignificant effect on the PIP or ICTP concentration.     

Intercalary femur and tibia segmental allografts provide an acceptable alternative in reconstructing tumor resections

Intercalary femur and tibia segmental allografts were implanted in 59 consecutive patients after segmental resection-52 for malignant and seven for benign aggressive bone tumors. The patients were followed up for an average of 5 years. Allograft survival was determined with the Kaplan-Meier method. Infection, fracture, and nonunion rates were determined. The overall 5-year survivorship for the 59 intercalary allografts was 79%, and we found no significant differences between allograft survival in patients receiving or not receiving adjuvant chemotherapy. Infection and fracture rates were 5% and 7% respectively. From 118 host-donor junctions, 11 did not initially heal (9%). The nonunion rate (10 of 69 osteotomies) for diaphyseal junctions was higher than the rate (one of 49 osteotomies) for metaphyseal junctions. Although some patients required reoperations because of allograft complications, it seems that the use of intercalary allograft clearly has a place in the reconstruction of a segmental defect created by the resection of a tumor in the diaphyseal and /or metaphyseal portion of the femur or tibia.     

Iridoids as allelochemicals and DNA polymerase inhibitors

Growth inhibitory activities and nutritional indices of catalpol (1), 8-O-acetylharpagide (2), and harpagide (3) were determinated in larvae and adults of Tribolium castaneum, respectively. Compound 1 produced a series of allelochemical effects probably related with the DNA synthesis. This iridoid possessed the highest inhibitory activity against DNA polymerase. Molecular orbital calculations suggest that a pi-pi charge transfer recognition model could explain the action of iridioids toward nucleic acid synthesis.     

Effects of aminoguanidine and cyclooxygenase inhibitors on nitric oxide and prostaglandin production, and nitric oxide synthase and cyclooxygenase expression induced by lipopolysaccharide in the estrogenized rat uterus

BACKGROUND/OBJECTIVE: The aim of our study was first to investigate if there exists an interaction between nitric oxide (NO) and prostaglandin (PG) generation in the estrogenized rat uterus challenged by lipopolysaccharide (LPS), and, secondly, which isoforms of nitric oxide synthase (NOS) and cyclooxygenase (COX) participate in this process. METHODS: To study the effect of LPS and to characterize the isoenzymes involved in the process, specific inhibitors of iNOS (aminoguanidine) and COX-II (meloxicam, nimesulide) and non-specific of COX (indomethacin) were injected intraperitoneally to determine their effect on NO and PG production, and on NOS and COX expression induced by LPS in estrogenized rat uterus. NO production was measured by arginine-citrulline conversion assay and PGE(2)/PGF(2alpha,)by radioconversion. Enzyme expression was evaluated by Western blot analysis. RESULTS: The present work shows that iNOS inhibitor, aminoguanidine, reduced NO and PGE(2)/PGF(2alpha) production induced by LPS injection. Aminoguanidine exerts its effect over the PG metabolism by inhibiting COX-II activity and expression. On the other hand, both indomethacin, a non-selective PG inhibitor, and meloxicam, a COX-II inhibitor, stimulated NO production and reduced PGE(2)/PGF(2alpha) generation. Indomethacin also reduced COX-II and iNOS expression. CONCLUSION: These results indicate that in the estrogenized rat uterus challenged with LPS, PG and NO interact affecting each other's metabolic pathways. The above findings indicate that the interaction between NOS and COX might be important in the regulation of physiopathologic events during pregnancy.     

IL-10 inhibits nitric oxide synthesis in murine uterus

OBJECTIVES: Recent reports point to a role for the nitric oxide/nitric oxide synthase (NO/NOS) system in implantation. It has been suggested that inducible NOS expressed at peri-implantation would lead to enhanced NO production, which could promote the attachment of the blastocyst. Short-term administration of NO donors during the pre-implantation period reduced the pregnancy rate in a dose-dependent manner. Thus, it is thought that optimal levels of NO are critical for embryo implantation, so regulation of NOS must be crucial. Taking this into consideration, interleukin-10 (IL-10), synthesized and secreted by the embryo, could be modulating NOS during implantation. In this study we have investigated the in vitro effect of IL-10 on NOS in the uterus. METHODS: To determine the effect of IL-10, slices of uterus from estrogenized mice were pre-incubated for 60 min with different concentrations of IL-10 and NOS activity was measured. RESULTS: IL-10 (50 and 100 ng/ml in vitro) diminished NOS activity. The in vivo administration of lipopolysaccharide (LPS; 8 mg/kg) significantly increased the conversion of arginine into citrulline. This effect was abolished after 60 min of preincubation with IL-10 (100 ng/ml). The stimulatory effect of LPS and estrogen on NOS activity is exerted on the Ca-independent isoform and IL-10 in vitro abolished this increase. We observed that the uterus of pregnant mice on day 5 of gestation synthesized NO. This production was significantly inhibited by preincubation with IL-10 (100 ng/ml). CONCLUSIONS: This report demonstrates that IL-10 is capable of inhibiting NO synthesis in estrogenized, LPS-treated and pregnant rat uterus.     

Living with pain: an existential focus

In the routine of a hospital, during my nursing practice of providing care to patients with pain, it was shown to me as reaching beyond a biological sphere included in an existential dimension. Something in this experience disturbed me and I felt the need to understand these people suffering from pain, asking how they understand their pain and what is the meaning of experiencing painful chronic situations. In the attempt to find a way to obtain such understanding, I searched for some ideas stemming from phenomenology. Then, I interviewed the subjects individually based on the central question: "How is your experience with pain? Tell me about this". After the analysis, I was able to understand that pain is a way to narrow the horizon of possibilities and transformations in existence. It is not only the physical body that is ill, but also life is affected in its various dimensions, fundamentally with regard to the family, work and self-relation world.     

Bioactive alkyl phenols and embelin from Oxalis erythrorhiza

The benzoquinone embelin and four alkyl phenols were isolated from an Argentinean collection of Oxalis erythrorhiza. 3-Heptadecyl-5-methoxy-phenol is reported for the first time. The structures were determined by spectroscopic methods. Embelin presented inhibitory effect on methicillin-resistant Staphylococcus aureus, Escherichia coli and the dermatophytic fungi Epidermophyton floccosum, Microsporum canis, Microsporum gypseum, Trichophyton mentagrophytes and Trichophyton rubrum with MICs ranging between 50 and 100 microg/ml. Furthermore, embelin was active against Trypanosoma cruzi trypomastigotes with 100% lysis at 100 microg/ml and cytotoxicity below the trypanocidal concentration. The new alkyl phenol 3-heptadecyl-5-methoxy-phenol was active towards Leishmania amazonensis and Leishmania donovani promastigotes with 100% lysis at 100 microg/ml. The cytotoxicity (IC50) of embelin and the new alkyl phenol on human lung fibroblasts were 739 and 366 microM, respectively. The plant is used to treat heart complains, a symptomatology related to Chagas' disease which is endemic in the San Juan Province, Argentine.     

One-year expression from high-capacity adenoviral vectors in the brains of animals with pre-existing anti-adenoviral immunity: clinical implications.

The main challenge of gene therapy is to provide long-term, efficient transgene expression. Long-term transgene expression from first generation adenoviral vectors (Advs) delivered to the central nervous system (CNS) is elicited in animals not previously exposed to adenovirus (Ad). However, upon systemic immunization against Ad, transgene expression from a first generation Adv is abolished. High-capacity Advs (HC-Advs) provide sustained very long-term transgene expression in the brain, even in animals pre-immunized against Ad. In this study, we tested the hypothesis that a HC-Adv in the brain would allow for long-term transgene expression, for up to 1 year, in the brain of mice immunized against Ad prior to delivery of the vector to the striatum. In na?ve animals, the expression of beta-galactosidase from Adv or HC-Adv was sustained for 1 year. In animals immunized prior to vector delivery, expression from a first generation Adv was abolished. These results point to a very long-term HC-Adv-mediated transgene expression in the brain, even in animals that had been immunized systemically against Ad before the delivery of HC-Adv into the brain. This study therefore indicates the utility of HC-Adv as a powerful gene therapy vector for chronic neurological disorders, even in patients who had been pre-exposed to Ad prior to gene therapy.     

Laparoscopic Approach to Colonic Perforation due to Colonoscopy

Background  

Iatrogenic perforation due to colonoscopy is the most serious complication of this procedure. Usually, resolution of this event requires segmental resection. The laparoscopic approach could be an option to minimize the outcome of this complication. The aim of the present study was to assess the effectiveness of the laparoscopic approach in treating colonic perforations due to colonoscopy.