Group Iv Research Articles

Hypnotic interaction between midazolam and different doses of propofol

Objective To evaluate the hypnotic interaction between midazolam and different doses of propofol. Methods One hundred and twenty ASA Ⅰor Ⅱpatients (43 male, 77 female) aged 18-60 yr weighing 40-80 kg undergoing elective surgery were randomly divided into 4 groups (n=30 each):group Ⅰmidazolam (M); group Ⅱ propofol (P) and group Ⅲ, Ⅳ midazolam + propofol (MP1, MP2). Six doses of midazolam (0.04, 0.06, 0.08, 0.1, 0.12, 0.15 mg/kg) and propofol (0.8, 1.0, 1.2, 1.5, 1.8 mg/kg) were given iv in group M and P respectively. OAA/S scale was used to assess the level of sedation (5=alert, 1=only responds to squeezing deltoid muscle). The hypnotic end point was defined as an OAA/S score ≤2. The level of sedation was assessed at 3 min after midazolam administration in group M and at 1 min after propofol administration in group P, MP1and MP2 . ED50 (95 % confidence intervals,95 % CI) of midazolam and propofol were determined by probit analysis in group M and P. Isobolographic analysis was used to analyze the interaction between the two drugs. The ratio of ED50 of midazolam to ED50 of propofol was 1:13 in group MP1 and 1:10 in group MP2 . Results The ED50 (95 % CI) of midazolam for hypnosis was 0.088 (0.066-0.110), 0.031 (0.026-0.036) and 0.045 (0.040-0.049) mg/kg respectively in group M, MP1 and MP2. The ED50 (95% CI) of propofol for hypnosis was 1.142(0.933-1.350), 0.421 (0.343-0.480), 0.450 (0.399-0.491) mg/kg respectively in group P, MP1,MP2. Isobolographie analysis confirmed that midazolam and propofol interacted synergistically at the ratio of 1: 13in group MP1 and additively at the ratio of 1:10 in group MP2 . Conclusion Midazolam and propofol interact synergistically at the ratio of 1:13 but additively at the ratio of 1:10. Key words: Propofol; Midazolam; Dose-response relationship, drug; Drug interactions; Hypnosis, anesthetic

L-Ascorbic acid partially protects two cycles of cisplatin chemotherapy-induced testis damage and oligo-astheno-teratospermia in a mouse model

Cisplatin ( cis-diaminedichloroplatinum-II) is a widely used antineoplastic agent in the treatment of a variety of cancers. The aim of the present study was to investigate the testicular toxicity of cisplatin in mice at human therapeutic dose-levels, and to investigate any protective effects of concomitantly administered l-ascorbic acid (i.p.; 10 mg/kg). Adult male BALB/C mice (13–15-week-old) were treated (i.p.) with two cycles of 5 days each of cisplatin with 17 days of recovery period between cycles, as follows: Group I (G-I) – water ( N=10); Group II (G-II) – l-ascorbic acid ( N=6); Group III (G-III) – 1 mg/kg ( N=6); Group IV (G-IV) – 1 mg/kg+ l-ascorbic acid ( N=6); Group V (G-V) – 2.5 mg/kg ( N=6); and Group VI (G-VI) – 2.5 mg/kg+ l-ascorbic acid ( N=8). All animals were sacrificed on third day after the last treatment. The testis weight was decreased in a dose-dependent pattern (G-III – 44% and G-V – 54% against G-I), but l-ascorbic acid (10 mg/kg) recovered the lost weight in G-VI up to 32% against G-V ( p<0.05). Seminiferous tubular pathology was indicated by vacuoles, epithelial gaps, epithelial sloughing, delayed spermiation, malorientation of spermatids, germ cell degeneration, phagocytosis of spermatids, multinucleated germ cell formation and atrophy. Structurally abnormal tubules (G-III – 33%; G-V – 100%) were induced, and protective effects were seen in G-IV (77%) and G-VI (25%; p<0.05). The tubular diameter was decreased in G-III–VI, but recovery was seen only in G-IV. The epithelial height was decreased in G-III, G-V and G-VI and the recovery was seen only in G-VI. The sperm count was decreased up to 53% and 71% against control in G-III and G-V, respectively, and recovery up to 47% and 61% was observed in G-IV and G-VI, respectively. The sperm motility was decreased up to 56% and 63% against control in G-III and G-V, respectively, and recovery was only marginal in G-IV and G-VI ( p>0.05). Total sperm abnormalities were increased in G-III–V (274%, 156% and 232%, respectively, p<0.05) and l-ascorbic acid protected the effect in G-VI up to 156% ( p<0.05). In conclusion, at human therapeutic dose-levels, cisplatin induces testicular damage and spermato-toxicity. l-Ascorbic acid only partially nullifies the gonadotoxic effects of cisplatin.

Intraoperative training on the techniques of sentinel node biopsy in breast cancer.

Abstract Abstract #1016 Background: Sentinel node biopsy (SNB) is an accurate procedure for axillary staging and the surgeons' experience is crucial for its proper application. A training session involving 20-30 cases is widely practiced. In order to speed up this learning curve, surgeons were trained intraoperatively by one instructor. The purpose of this report was to evaluate the procedure by comparing the results of the instructor with those of the trainees.&amp;#x2028; Material and Methods: Patients with invasive breast cancer (T0-T2[&amp;lt;3cm]N0M0) were considered eligible. Lymphatic mapping was obtained by peritumoral or periareolar injections of technetium with or without blue dye. Complementary axillary lymph node (LN) dissection was performed when SNB was unsuccessful or when SN were positive. Patients were distributed in 4 groups : (i) teacher's learning curve (SNB followed by complementary axillary dissection) (n=40), (ii) SNB by instructor (n=130), (iii) SNB by trainees with supervision from instructor (n=63), and (iv) SNB by trainees alone (n=303). The criteria of patients' selection, the parameters of success of the SNB procedure, and the LN metastases were compared. Reported p-values compare groups (ii) to (iv).&amp;#x2028; Results : From May 1999 to December 2007, 808 patients underwent a SNB. The SN identification rate was 98% in the group (i), 98% in the group (ii), 97% in the group (iii), and 99% in the group (iv) (p=0.196). SN were positive in respectively 28%, 31%, 28%, and 29% of patients. Overall positive nodes (SN and LN) were diagnosed in respectively 28%, 31%, 30%, and 30% of patients (p=0.833). The distribution of isolated tumor cells, micrometastases, and metastases was not statistically different between the four groups (p=0.163).&amp;#x2028; Conclusion: These comparable results confirm the success with which the SNB was taught. This strategy avoided the 20-30 SNB with complementary axillary dissection. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1016.

Registration of S99‐2281 Soybean Germplasm Line with Resistance to Frogeye Leaf Spot and Three Nematode Species

Soybean [Glycine max (L.) Merr.] germplasm line S99‐2281 (Reg. No. GP‐361, PI 654356) was developed at the University of Missouri–Delta Center and released by the University of Missouri Agricultural Experiment Station. It is an F4 plant selection composited in the F5 generation from the cross of N90‐516 × S92‐1069. S99‐2281 is a productive, early group V (relative maturity 5.2) soybean line with broad resistance to soybean cyst nematode (Heterodera glycines Ichinohe) HG types (races), southern root knot nematode [Meloidogyne incognita (Kofoid &amp; White) Chitwood], and reniform nematode [Rotylenchulus reniformis (Linford and Oliveira)]. It also carries the Rcs3 gene for resistance to all known races of frogeye leaf spot, caused by Cercospora sojina K. Hara. In combined analyses over 3 yr, S99‐2281 yielded 3 and 7% more than ‘Manokin’ in southeast Missouri trials (15 tests) and in Uniform Group IVs Tests–Southern States (39 tests), respectively. It will be useful as an elite parent in soybean breeding programs to develop productive soybean cultivars with broad resistance to frogeye leaf spot and resistance to multiple nematode species.

Diverse Range of Mineralization Induced by Phase Separation of Hydrothermal Fluid: Case Study of the Yonaguni Knoll IV Hydrothermal Field in the Okinawa Trough Back‐Arc Basin

AbstractThe Yonaguni Knoll IV hydrothermal vent field (24°51′N, 122°42′E) is located at water depths of 1370–1385 m near the western edge of the southern Okinawa Trough. During the YK03–05 and YK04–05 expeditions using the submersible Shinkai 6500, both hydrothermal precipitates (sulfide/sulfate/carbonate) and high temperature fluids (Tmax = 328°C) presently venting from chimney‐mound structures were extensively sampled. The collected venting fluids had a wide range of chemistry (Cl concentration 376–635 mmol kg−1), which is considered as evidence for sub‐seafloor phase separation. While the Cl‐enriched smoky black fluids were venting from two adjacent chimney‐mound structures in the hydrothermal center, the clear transparent fluids sometimes containing CO2 droplet were found in the peripheral area of the field. This distribution pattern could be explained by migration of the vapor‐rich hydrothermal fluid within a porous sediment layer after the sub‐seafloor phase separation. The collected hydrothermal precipitates demonstrated a diverse range of mineralization, which can be classified into five groups: (i) anhydrite‐rich chimneys, immature precipitates including sulfide disseminations in anhydrite; (ii) massive Zn‐Pb‐Cu sulfides, consisting of sphalerite, wurtzite, galena, chalcopyrite, pyrite, and marcasite; (iii) Ba‐As chimneys, composed of barite with sulfide disseminations, sometimes associated with realgar and orpiment overgrowth; (iv) Mn‐rich chimneys, consisting of carbonates (calcite and magnesite) and sulfides (sphalerite, galena, chalcopyrite, alabandite, and minor amount of tennantite and enargite); and (v) pavement, silicified sediment including abundant native sulfur or barite. Sulfide/sulfate mineralization (groups i–iii) was found in the chimney–mound structure associated with vapor‐loss (Cl‐enriched) fluid venting. In contrast, the sulfide/carbonate mineralization (group iv) was specifically found in the chimneys where vapor‐rich (Cl‐depleted) fluid venting is expected, and the pavement (group v) was associated with diffusive venting from the seafloor sediment. This correspondence strongly suggests that the subseafloor phase separation plays an important role in the diverse range of mineralization in the Yonaguni IV field. The observed sulfide mineral assemblage was consistent with the sulfur fugacity calculated from the FeS content in sphalerite/wurtzite and the fluid temperature for each site, which suggests that the shift of the sulfur fugacity due to participation of volatile species during phase separation is an important factor to induce diverse mineralization. In contrast, carbonate mineralization is attributed to the significant mixing of vapor‐rich hydrothermal fluid and seawater. A submarine hydrothermal system within a back‐arc basin in the continental margin may be considered as developed in a geologic setting favorable to a diverse range of mineralization, where relatively shallow water depth induces sub‐seafloor phase separation of hydrothermal fluid, and sediment accumulation could enhance migration of the vapor‐rich hydrothermal fluid.

Parallel post‐space preparation in different tooth types ex vivo: deviation from the canal centre and remaining dentine thickness

To determine the deviation of parallel-sided twist-drills during post-channel preparation and relate this to tooth type and position. Human teeth with single root canals were selected: maxillary second premolars (group i); maxillary lateral incisors (group ii); mandibular canines (group iii); mandibular first premolars (group iv; all groups n = 16). The teeth were reduced to 17 mm length by sectioning the crown, and the root canals prepared and filled. Microradiographs were made in two directions. The teeth were individually embedded in a gypsum jaw and placed in a phantom head. Two operators performed parallel post-space preparation (12 mm length, 1.25 mm diameter) to the following protocol: gutta-percha removal with Gates Glidden drills numbers 2 and 3 and post-space enlargement with parallel drills numbers 3, 4 and 5, consecutively. Subsequently, microradiographs were re-exposed. The original and post-operative microradiographs were digitized and superimposed, and deviation of the post-space from the filled canal and remaining dentine thickness measured. Overall, the mean deviation was 0.07 mm to the mesial (95% CI: 0.01-0.12), and 0.27 mm to the buccal (95% CI: 0.18-0.35). Group ii had significantly more buccal deviation than other groups (P = 0.004-0.008). A remaining dentine thickness of <0.5 mm occurred 16 times in 14 teeth, and of <1 mm occurred 97 times in 52 teeth. Deviation during parallel post-preparation was common, predominantly in mesial and buccal directions, especially in maxillary incisors. This deviation increased the risk of perforation considerably.

Design of organometallic group iv heteroallylic complexes and their catalytic properties for polymerizations and olefin centered transformations

The use of metallocenes in many stoichiometric and catalytic processes has been the impetus for the development of new organometallic complexes, especially those containing early transition metals. The formation of coordinative unsaturated complexes using allylic, benzamidinate and aminopyridine families is presented. The synthesis and structural parameters of the new complexes, their activation and use in the polymerization of alpha-olefins and dienes, in the dehydrogenative coupling of silanes and in the hydroamination reactions comprise the objectives of this review.

239 EMBRYOTOXICITY ASSAY FOR ANTIVIRAL COMPOUND BPIP (5-[(4-BROMOPHENYL)METHYL]-2-PHENYL-5H-IMIDAZO[4,5-c]PYRIDINE) IN BOVINE IN VITRO-PRODUCED EMBRYOS

Bovine viral diarrhea virus (BVDV) causes serious economic losses in the cattle industry. Evidence exists that only zona pellucida (ZP)-free bovine embryos are susceptible to BVDV infection (Vanroose et al. 1998 Biol. Reprod. 58, 857–866); however, BVDV can adhere to and therefore ‘infect’ both in vivo-(Waldrop et al. 2004 Theriogenology 62, 387–397) and in vitro-produced ZP intact embryos (Stringfellow et al. 2000 Theriogenology 53, 827–839). To eliminate these sanitary risks, pre-treatment of embryos with antiviral compounds may be a promising approach (Givens et al. 2006 Theriogenology 65, 344–355). BPIP (5-[(4-bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine) has been reported to display antiviral activity against BVDV, with a 50% effective inhibition of BVDV-induced cytopathic effect formation at a concentration of 0.04 µM (Paeshuyse et al. 2006 J. Virol. 80, 149–160). However, since the short- and long-term effects of BPIP have not been described, the aim of the current study was to assess whether addition of BPIP for 2 days at a concentration of 5 µM is toxic for ZP-free cattle embryos. Oocytes were aspirated from 3–6-mm follicles of cattle ovaries, matured for 24 h, and subsequently co-incubated with 1 × 106 sperm cells mL−1 in IVF-TALP with 20 µg/mL−1 heparin for 24 h at 39°C and 5% CO2 in air. After fertilization, presumptive zygotes were put in groups of 25 into 50-µL droplets of SOF under oil in 5% CO2, 5% O2, and 90% N2 for 6 days. Afterwards, morulae and blastocysts were collected, rendered ZP-free by means of pronase treatment, and divided into 4 groups: (i) ZP-free control group, (ii) ZP-free control group treated with a volume of DMSO equal to condition (iv), (iii) ZP-free group treated with 5 µM BPIP in DMSO, and (iv) ZP-free group treated with 10 µM BPIP in DMSO. Because BPIP is a fat-soluble molecule, embryos were cultured in 0.5 mL SOF without oil for 2 days. At Day 8, all embryos were fixed, TUNEL-stained, and analyzed for total cell number and percentage of apoptotic cells. Three independent replicates were performed. Results are shown in Table 1 and were analyzed by means of ANOVA. Only group iv showed a significant decrease in total cell number, indicating that at 10 µM BPIP may negatively influence embryo development. At both 5 and 10 µM, BPIP treatment resulted in an increase in percentage of apoptotic cells compared to the control group. However, a similar increase was observed using DMSO alone (group ii), indicating that the apoptotic effect may be due solely to the DMSO. In conclusion, BPIP does not appear to cause embryo toxicity at 5 µM, but an alternative, less toxic, dissolving agent may be considered. Table 1.Embryotoxicity assay of BPIP

Identifying the bacterial community on the surface of Intralox™ belting in a meat boning room by culture-dependent and culture-independent 16S rDNA sequence analysis

We examined the bacterial community present on an Intralox™ conveyor belt system in an operating lamb boning room by sequencing the 16S ribosomal DNA (rDNA) of bacteria extracted in the presence or absence of cultivation. RFLP patterns for 16S rDNA clone library and cultures were generated using HaeIII and MspI restriction endonucleases. 16S rDNA amplicons produced 8 distinct RFLP pattern groups. RFLP groups I–IV were represented in the clone library and RFLP groups I and V–VIII were represented amongst the cultured isolates. Partial DNA sequences from each RFLP group revealed that all group I, II and VIII representatives were Pseudomonas spp., group III were Sphingomonas spp., group IV clones were most similar to an uncultured alpha proteobacterium, group V was similar to a Serratia spp., group VI with an Alcaligenes spp., and group VII with Microbacterium spp. Sphingomonads were numerically dominant in the culture-independent clone library and along with the group IV alpha proteobacterium were not represented amongst the cultured isolates. Serratia, Alcaligenes and Microbacterium spp. were only represented with cultured isolates. Pseudomonads were detected by both culture-dependent (84% of isolates) and culture-independent (12.5% of clones) methods and their presence at high frequency does pose the risk of product spoilage if transferred onto meat stored under aerobic conditions. The detection of sphingomonads in large numbers by the culture-independent method demands further analysis because sphingomonads may represent a new source of meat spoilage that has not been previously recognised in the meat processing environment. The 16S rDNA collections generated by both methods were important at representing the diversity of the bacterial population associated with an Intralox™ conveyor belt system.

PGE2 release is independent of upregulation of Group V phospholipase A2 during long-term stimulation of P388D1 cells with LPS

P388D1 cells release arachidonic acid (AA) and produce prostaglandin E2 (PGE2) upon long-term stimulation with lipopolysaccharide (LPS). The cytosolic Group IVA (GIVA) phospholipase A2 (PLA2) has been implicated in this pathway. LPS stimulation also results in increased expression and secretion of a secretory PLA2, specifically GV PLA2. To test whether GV PLA2 contributes to PGE2 production and whether GIVA PLA2 activation increases the expression of GV PLA2, we utilized the specific GIVA PLA2 inhibitor pyrrophenone and second generation antisense oligonucleotides (AS-ONs) designed to specifically inhibit expression and activity of GV PLA2. Treatment of P388D1 cells with antisense caused a marked decrease in basal GV PLA2 mRNA and prevented the LPS-induced increase in GV PLA2 mRNA. LPS-stimulated cells release active GV PLA2 into the medium, which is inhibited to background levels by antisense treatment. However, LPS-induced PGE2 release by antisense-treated cells and by control cells are not significantly different. Collectively, the results suggest that the upregulation of GV PLA2 during long-term LPS stimulation is not required for PGE2 production by P388D1 cells. Experiments employing pyrrophenone suggested that GIVA PLA2 is the dominant player involved in AA release, but it appears not to be involved in the regulation of LPS-induced expression of GV PLA2 or cyclooxygenase-2.

Depth of delayed cooling alters neuroprotection pattern after hypoxia‐ischemia

Hypothermia after perinatal hypoxia-ischemia (HI) is neuroprotective; the precise brain temperature that provides optimal protection is unknown. To assess the pattern of brain injury with 3 different rectal temperatures, we randomized 42 newborn piglets: (Group i) sham-normothermia (38.5-39 degrees C); (Group ii) sham-33 degrees C; (Group iii) HI-normothermia; (Group iv) HI-35 degrees C; and (Group v) HI-33 degrees C. Groups iii through v were subjected to transient HI insult. Groups ii, iv, and v were cooled to their target rectal temperatures between 2 and 26 hours after resuscitation. Experiments were terminated at 48 hours. Compared with normothermia, hypothermia at 35 degrees C led to 25 and 39% increases in neuronal viability in cortical gray matter (GM) and deep GM, respectively (both p < 0.05); hypothermia at 33 degrees C resulted in a 55% increase in neuronal viability in cortical GM (p < 0.01) but no significant increase in neuronal viability in deep GM. Comparing hypothermia at 35 and 33 degrees C, 35 degrees C resulted in more viable neurons in deep GM, whereas 33 degrees C resulted in more viable neurons in cortical GM (both p < 0.05). These results suggest that optimal neuroprotection by delayed hypothermia may occur at different temperatures in the cortical and deep GM. To obtain maximum benefit, you may need to design patient-specific hypothermia protocols by combining systemic and selective cooling.

Group IV cytosolic phospholipase A 2 mediates arachidonic acid release in H9c2 rat cardiomyocyte cells in response to hydrogen peroxide

Damaging reactive oxygen species are released during episodes of ischemia and reperfusion. Some cellular adaptive responses are triggered to protect the injured organ, while other cascades are triggered which potentiate the damage. In these studies, we demonstrate that rat cardiomyocte H9c2 cells release arachidonic acid in response to hydrogen peroxide. In H9c2 cells, arachidonic acid release is attenuated by methyl arachidonyl fluorophosphonate (MAFP) and pyrrophenone, indicating that a phospholipase A 2 Group IV enzyme mediates arachidonic acid mobilization. Moreover, hydrogen peroxide alters the cellular morphology of the H9c2 cells, causing drastic cell shrinkage. Because MAFP and pyrrophenone prevent the morphological alterations caused by hydrogen peroxide, these studies show that phospholipase A 2 Group IV activity is likely integrally involved in the damage initiated by hydrogen peroxide.

Thyroid evaluation in HIV-1-infected patients

ABSTRACT : Reports on thyroid function in patients infected by the human immunodeficiency virus (HIV-1) have been scanty and contradictory. Until now, it has not been found any Brazilian publication about this subject. Thus, this study was carried out in order to evaluate the thyroid function at different stages of HIV-1 infection and to determine if the alterations in thyroid function tests could be useful to predict the progression of the disease and the patient outcome. Eighty-five HIV-1-infected patients aging 17 to 63 years old (mean=32), and 16 healthy volunteers aging 17 to 62 years old (mean=36) participated in this prospective study. Total triiodothyronine (T3), total thyroxine (T4), free thyroxine (FT4), thyrotropin (TSH), responsiveness to thyrotropin-releasing hormone (TRH), and T lymphocytes CD4 + and CD8 + cells were measured. Individual variables were compared between four groups: Group I (GI) – 16 healthy volunteers; Group II (GII) – 30 HIV-1-infected individuals with more than 200 CD4+ cells/mm³; Group III (GIII) – 30 AIDS patients with 200 CD4+ cells/mm³ or less, and without opportunistic infection; Group IV (GIV) – 25 patients with 200 CD4+ cells/mm³ or less, and with opportunistic infection. There were 75 survivors and 10 deaths after three months of follow-up. The results showed that 53 patients (62.3%) presented some kind of abnormality in the thyroid function tests. Primary hypothyroidism was found in 25 patients (29.4%), and alterations compatible with euthyroid sick syndrome were observed in 28 patients (32.9%). Serum T4 levels were not different between the groups, but serum T3 levels were lower in GIV patients (p<0.001), and serum TSH levels were lower in GIII patients, when compared to healthy controls. There was a positive correlation between serum T3 levels and mortality (p=0.004). Based on these results, it was possible to conclude that abnormalities in thyroid function tests are frequently observed in HIV-1-infected patients, and that a decline in serum T3 levels may provide a prognosis for this infection.

Dextrose in the banked blood products does not seem to affect the blood glucose levels in patients undergoing liver transplantation

Hyperglycemia commonly seen in liver transplantation (LT) has often been attributed to the dextrose in the storage solution of blood transfusion products. The purpose of the study is to compare the changes of the blood glucose levels in transfused and non-transfused patients during LT. A retrospective study on 60 biliary pediatric patients and 16 adult patients undergoing LT was carried out. Transfused pediatric patients were included in Group I (GI), those not transfused in Group II (GII). Twelve adult patients were not given transfusion and assigned to Group III (GIII); whereas, four adult patients who received massive transfusion were assigned to Group IV (GIV). The blood glucose levels, volume of blood transfused, and the volume of crystalloid infused were recorded, compared and analyzed. Results showed that the changes in blood glucose levels during LT for both non-transfused and minimally transfused pediatric groups and non-transfused and massively-transfused adult groups were almost the same. We conclude that blood transfusion does not cause significant changes in the blood glucose levels in this study.

COMPARISON OF MORBIDITY AND MORTALITY BETWEEN PRIMARY AND SECONDARY PROPHYLAXIS WITH ENDOSCOPIC VARICEAL LIGATION (EVL) FOR ESOPHAGEAL VARICES

Purpose: Endoscopic variceal ligation (EVL) is routinely employed in the secondary prophylaxis of esophageal varices and in their primary prophylaxis if they are large and not amenable to beta-blockers. We reviewed the outcomes and complications of EVL at a tertiary referral center. Methods: Retrospective chart review of 104 patients who underwent EVL during atwo year period. Grade II and above esophageal varices were banded on average every 4 to 6 weeks until obliteration. Nonselective betablockers (NSB) when used were titrated to a pulse between 55 and 60. Results: 104 patient charts were reviewed for a total 178 procedures of which there were 115 EVLs for primary and 63 for secondary prophylaxis. The etiology of liver disease was similar in both groups with Hepatitis C and alcohol being the most common. The mean number of bands placed per procedure in the primary prophylaxis group(PPG) was 3 vs. 4 in the secondary prophylaxis group (SPG). The mean grade of esophageal varices was III in the primary group and IV in the secondary group. The incidence of portal hypertensive gastropathy, GAVE, and gastric varices was the same in both groups. In the PPG 33/59 (56%) were on nonselective betablockers vs. 10/48 (21%) in the SPG. Over a 3 yr period, in the PPG 6/59 patients experienced variceal bleeding. Of those 6 patients, 2 were minor bleeds secondary to superficial ulcers from the banding procedure. One patient had significant chest pain post procedure that subsided in 48 hours. There were no deaths related to variceal bleeding. 6/45 patients bled in the in the SPG from varices. There was one bleed from an ulcer related to the EVL. There was one mortality in the SPG related to bleeding from esophageal varices inspite of regular EVLs. Therefore overall adverse events from EVL in both groups together were low (2.2%). Of 14 patients who were on a non selective betablocker 5 had variceal bleeding. Conclusions: In our study the risk of recurrent variceal bleeding is reduced to less than 15% in 3 yr period (significant reduction from a 75% rate of rebleed in one year without treatment). Also the risk of variceal bleed in patients who have never bled before with EVL for primary prophylaxis in our study was 10% over 3 years. This study also revealed that EVL forprimary prophylaxis has a low rate of adverse events(5%). The role of combined pharmacotherapy and EVL is not a routine practice (21–56%) and its efficacy needs to be further evaluated with prospective trials.

Synthesis of Group IVB Metals Oxicarbides by Carboreduction Reactions

The metals of the group IV B (Ti, Zr, Hf) present a series of carbides and oxicarbides with scientific and technological interest. Many of these compounds belong to the subsystem MO - MC of the pseudoternary MO - MN - MC system (where M = Ti, Zr or Hf). In this work carboreduction reactions of TiO2 and ZrO2 were performed in argon atmosphere, using temperatures from 1250° to 1650° and reaction times of 120 min. The oxicarbides obtained were in the range TiC0.16O0.84 to TiC0.73O0.27 and ZrC0.46O0.54 to ZrC0.90O0.10. respectively. The reaction products were characterized by X-ray diffraction (XRD), with the calculation of their cell constants by means of the Rietveld method. Scanning Electron Microscopy (SEM) was used in the characterization of powdered materials. Additionally, the carborreduction reaction was followed by weight loss.

THE EFFECTS OF DEXAMETHASONE ON LIPID PEROXIDATION AND NITRIC OXIDE LEVELS ON THE HEALING OF TRACHEAL ANASTOMOSES: AN EXPERIMENTAL STUDY IN RATS

Corticosteroids are shown to have deleterious effects on wound healing for various tissues. Arginine metabolism and nitric oxide (NO) synthesis play an important role in many aspects of inflammation and wound healing. The study was designed to evaluate the relationship of dexamethasone impaired healing of tracheal anastomoses to NO metabolism and lipid peroxidation. Forty-two adult Wistar rats were randomly divided into five groups. The animals underwent tracheal transection and primary anastomoses. The groups were assigned as follows: Group I (GI) (sham, N=6); Group II (GII) (control, N=6); Group III (GIII), dexamethasone, 0.1 mg kg −1 per day, intramuscularly for a week ( N=10); Group IV (GIV), dexamethasone, 1 mg kg −1 per day, intramuscularly for a week ( N=10); Group V (GV), dexamethasone, 6 mg kg −1 intramuscularly as a single dose ( N=10). After 7 days, bursting pressure was used to evaluate anastomotic healing. Serum nitrite/nitrate and malondialdehyde (MDA) levels were measured as an index of NO synthesis and lipid peroxidation, respectively. The bursting pressure significantly decreased in GIII and GIV when compared to the control group. The difference between GIII and GIV was also statistically significant. Nitrite/nitrate and MDA levels of GIII were found to be significantly higher than the control group. Also, the difference was found to be statistically significant between GIII and GIV in regard to nitrite/nitrate levels. The present study demonstrates that daily administration of dexamethasone for a week inhibits NO synthesis in a dose-dependent manner on tracheal anastomotic healing. Besides the generally accepted evaluation parameters including bursting pressure and hydoxyproline content; NO and MDA levels may be helpful in the assessment of wound healing especially for the investigation of impairment mechanism.

Dissociation between the circulating renin-angiotensin system and angiotensin II receptors in central losartan-induced hypertension.

Losartan, an AT1 angiotensin II (ANG II) receptor non-peptide antagonist, induces an increase in mean arterial pressure (MAP) when injected intracerebroventricularly (icv) into rats. The present study investigated possible effector mechanisms of the increase in MAP induced by icv losartan in unanesthetized rats. Male Holtzman rats (280-300 g, N = 6/group) with a cannula implanted into the anterior ventral third ventricle received an icv injection of losartan (90 micro g/2 micro l) that induced a typical peak pressor response within 5 min. In one group of animals, this response to icv losartan was completely reduced from 18 +/- 1 to 4 +/- 2 mmHg by intravenous (iv) injection of losartan (2.5-10 mg/kg), and in another group, it was partially reduced from 18 +/- 3 to 11 +/- 2 mmHg by iv prazosin (0.1-1.0 mg/kg), an alpha1-adrenergic antagonist (P<0.05). Captopril (10 mg/kg), a converting enzyme inhibitor, injected iv in a third group inhibited the pressor response to icv losartan from 24 +/- 3 to 7 +/- 2 mmHg (P<0.05). Propranolol (10 mg/kg), a beta-adrenoceptor antagonist, injected iv in a fourth group did not alter the pressor response to icv losartan. Plasma renin activity and serum angiotensin-converting enzyme activity were not altered by icv losartan in other animals. The results suggest that the pressor effect of icv losartan depends on angiotensinergic and alpha1-adrenoceptor activation, but not on increased circulating ANG II.

Effect of a homeopathic drug, Chelidonium, in amelioration of p-DAB induced hepatocarcinogenesis in mice.

BackgroundCrude extracts of Chelidonium majus, and also purified compounds derived from crude extracts of this plant, have been reported to exhibit anti-viral, anti-inflammatory, anti-tumor and anti-microbial properties both in vitro and in vivo. Chelidonium is a homeopathic drug routinely used against various liver disorders including cancer in humans. Two potencies of Chelidonium (Ch-30, Ch-200) have been tested for their possible anti-tumor and enzyme modulating activities in liver and anti-clastogenic effects during p-DAB-induced hepatocarcinogenesis in mice compared to suitable controls.MethodsSeveral cytogenetic and enzymatic protocols were used at three fixation intervals; at 60 days, 90 days and 120 days of treatment. Different sets of healthy mice were fed: i) hepatocarcinogen, p-DAB plus phenobarbital (PB), ii) only PB, iii) neither p-DAB nor PB (normal control). One set of mice fed with p-DAB plus PB was also fed Ch-30 (iv) and another set Ch-200 (v). All standard currently used methods were adopted for cytogenetical preparations and for the enzyme assays.ResultsAll group (i) mice developed tumors in liver at all fixation intervals, while none of group (ii) and (iii) mice developed any tumors. About 40% mice in group (iv) and group (v) did not show tumor nodules in their liver. Feeding of Chelidonium to group (iv) and (v) mice reduced genotoxic effects to a significant extent (p < 0.05 to p < 0.001).ConclusionThe homeopathic drug Chelidonium exhibited anti-tumor and anti-genotoxic activities and also favorably modulated activities of some marker enzymes. Microdoses of Chelidonium may be effectively used in combating liver cancer.

Katalizatory polimeryzacji olefin

The invention is a catalyst system including a Group IV B transition metal component and an alumoxane component which may be employed to polymerize olefins to produce a high molecular weight polymer.