Switching from originator recombinant growth hormone (Genotropin™) to biosimilar (CRISCY™): Results from a 6-month, multicentric, non-inferiority, extension trial.

OBJECTIVE: A previous 12-month comparative trial with Criscy™ (r-hGH Cristália), a biosimilar recombinant growth hormone, demonstrated equivalent efficacy and safety to Genotropin™. This extension trial evaluated the effects of switching patients treated with Genotropin™ to the biosimilar Criscy™ over an additional 6-month treatment period, comparing efficacy, safety, and immunogenicity parameters with patients remaining in the Criscy™ arm. DESIGN: This extension study included 11 research centers and 81 patients who participated in the CERES study (Czepielewski et al., 2019 [1]). Participants from the Genotropin™ arm (n = 39) had the drug replaced by Criscy™ and the remaining participants were kept in the Criscy™ arm (n = 42) for an additional 6-month period to evaluate immunogenicity, efficacy (growth rate, height SDS), and safety (laboratory tests, and adverse events). RESULTS: Before the switch, both Criscy™ and Genotropin groups were similar concerning demographics, and auxological measures: age, sex, height, height SDS, weight, and BMI. Height velocity (HV) after 18 months of treatment was 8.7 ± 1.56 cm/year for Criscy™ group and 8.9 ± 1.36 cm/year for Genotropin™ group in the ITT population (p = 0.43). The auxological parameters and IGF-1 and IGFBP-3 SDS were comparable between both groups of patients. No participants were excluded from the study due to adverse events. There were no clinical or statistical relevant differences between the treatment groups concerning frequency, distribution, intensity, and AEs outcome. Similarly, no new anti-r-hGH (ADA) cases among patients that switched from Genotropin™ to Criscy™ were reported. No neutralizing antibody (nAb) was detected in either group. CONCLUSIONS: This trial showed that switching from originator recombinant human growth hormone to Criscy™ had no impact on efficacy, safety, nor immunogenicity as compared to continued treatment with Criscy™. Growth rates and ADA incidence remained the same as seen before the switch.

Efficacy and safety of a biosimilar recombinant human growth hormone (r-hGH Cristalia) compared with reference r-hGH in children with growth hormone deficiency (CERES study): A randomized, multicentric, investigator-blind, phase 3 trial.

OBJECTIVE: The CERES study was a randomized, multicenter, investigator-blind trial aimed to evaluate the efficacy and safety of a recombinant human growth hormone (r-hGH) developed by Cristalia, as a biosimilar product, with analytical, functional and pharmacokinetics similarities comparable to Genotropin™, in children with growth hormone deficiency (GHD). DESIGN: A total of 135 naïve prepubertal children with GHD were recruited, of whom 97 were randomized in 14 Brazilian sites to received either r-hGH Cristalia (n = 49) or Genotropin™ (n = 48). Efficacy was evaluated considering the height standard deviation score (SDS) and growth velocity as auxological parameters, IGF-1 and IGFBP-3 were measured as pharmacodynamic parameters during 12 months treatment time. Safety was assessed by monitoring adverse events, immunogenicity, blood count with platelets, biochemical profile and hormonal levels particularly fasting glucose, insulin and HbA1C. RESULTS: The auxological parameters and IGF-1 and IGFBP-3 levels were comparable between both groups of patients. At end of study or the 12th month treatment, the means growth velocity was 9.7 cm/year and 9.5 cm/year, for r-hGH Cristalia and Genotropin™, respectively. The ANCOVA mean difference between the groups was 0.16 cm/year to Cristalia group (CI 95% = -0.72 to 1.03 cm/year). There was no difference in adherence among the treatment groups. The safety profile was comparable between groups. CONCLUSIONS: The clinical similarity between r-hGH and Genotropin™ was demonstrated within 12 month of treatment. On the basis of comparability of quality, safety, and efficacy to the reference product, r-hGH from Cristalia can be considered a cost-effective therapeutic option for patients with growth disorders.

Under-vaccinated groups in Europe and their beliefs, attitudes and reasons for non-vaccination; two systematic reviews.

BACKGROUND: Despite effective national immunisation programmes in Europe, some groups remain incompletely or un-vaccinated ('under-vaccinated'), with underserved minorities and certain religious/ideological groups repeatedly being involved in outbreaks of vaccine preventable diseases (VPD). Gaining insight into factors regarding acceptance of vaccination of 'under-vaccinated groups' (UVGs) might give opportunities to communicate with them in a trusty and reliable manner that respects their belief system and that, maybe, increase vaccination uptake. We aimed to identify and describe UVGs in Europe and to describe beliefs, attitudes and reasons for non-vaccination in the identified UVGs. METHODS: We defined a UVG as a group of persons who share the same beliefs and/or live in socially close-knit communities in Europe and who have/had historically low vaccination coverage and/or experienced outbreaks of VPDs since 1950. We searched MEDLINE, EMBASE and PsycINFO databases using specific search term combinations. For the first systematic review, studies that described a group in Europe with an outbreak or low vaccination coverage for a VPD were selected and for the second systematic review, studies that described possible factors that are associated with non-vaccination in these groups were selected. RESULTS: We selected 48 articles out of 606 and 13 articles out of 406 from the first and second search, respectively. Five UVGs were identified in the literature: Orthodox Protestant communities, Anthroposophists, Roma, Irish Travellers, and Orthodox Jewish communities. The main reported factors regarding vaccination were perceived non-severity of traditional "childhood" diseases, fear of vaccine side-effects, and need for more information about for example risk of vaccination. CONCLUSIONS: Within each UVG identified, there are a variety of health beliefs and objections to vaccination. In addition, similar factors are shared by several of these groups. Communication strategies regarding these similar factors such as educating people about the risks associated with being vaccinated versus not being vaccinated, addressing their concerns, and countering vaccination myths present among members of a specific UVG through a trusted source, can establish a reliable relationship with these groups and increase their vaccination uptake. Furthermore, other interventions such as improving access to health care could certainly increase vaccination uptake in Roma and Irish travellers.

Effects of physical exercise and social isolation on anxiety-related behaviors in two inbred rat strains.

We investigated the effects of physical exercise (PE) on locomotor activity and anxiety-like behavior in Lewis (LEW) and Spontaneously Hypertensive Rats (SHR) male rats. Rats received either four weeks of forced training, 5days/week, on a treadmill (experiment 1) or were given 21days of free access to running wheels (experiment 2). We also tested the effects of social isolation (SI) (seven days of isolation - experiment 3) on behavior. In experiment 1, 20% of LEW rats and 63% of SHR rats completed the training protocol. PE significantly increased central and peripheral locomotion in the open field (OF) and entries into the open arms in the elevated plus-maze (EPM) in both strains. In experiment 2, the distance traveled by SHR rats on running wheels was significantly higher compared with LEW rats. PE on running wheels also increased the time spent in the center of the OF in SHR rats only. In experiment 3, SI decreased central and peripheral locomotion in the OF in both strains. In summary, forced PE on a treadmill reduced anxiety-like behavior and increased locomotion in male rats of both strains, whereas voluntary PE on running wheels decreased anxiety-like behavior in SHR rats only. SI decreased locomotion in both strains in the OF. This study suggests that spontaneous activity levels are genotype-dependent and the effects of PE depend on the type of exercise performed.

Utilização do yacon ( Smallanthus sonchifolius ) na proteção contra colonização intestinal de frangos de corte infectados por Salmonella Enteritidis / Use of yacon (Smallanthus sonchifolius) protect against intestinal colonization of broilers infectes by Salmonella Enteritidis]

Os frutanos do tipo inulina são oligossacarídeos que favorecem a multiplicação de determinados gêneros bacterianos no intestino, promovendo um efeito prebiótico. Este trabalho avaliou o efeito da inulina extraída de raízes de yacon (Smallanthus sonchifolius) sobre a colonização intestinal de frangos de corte experimentalmente infectados por Salmonella Enteritidis. Sessenta frangos de corte com um dia de idade foram divididos em três grupos de tratamento, com duas repetições, criados até 21 dias. As aves do grupo yacon receberam 100mg de inulina/dia, via oral, por três dias consecutivos. No sétimo dia de vida, as aves tratadas e o controle positivo foram desafiados pela via oral com uma cultura de S. Enteritidis. Não foram observadas diferenças de desempenho zootécnico entre os grupos. O índice de infectividade das aves suplementadas com yacon foi menor até o sexto dia após o desafio, mas, ao término do experimento, foi superior ao controle positivo. Os dados deste trabalho demonstram que o uso da inulina nos três primeiros dias de vida promoveu uma redução da colonização intestinal dos frangos por Salmonella Enteritidis na primeira semana após o desafio. Novos estudos são necessários para determinar a dose e o tempo de tratamento ideal para um efeito protetor de maior duração.(AU)

The fructan inulin-type oligosaccharides favor the multiplication of some bacterial genera in the intestine, promoting a prebiotic effect. This study evaluated the effect of inulin extracted from yacon roots (Smallanthus sonchifolius) on intestinal colonization of broilers experimentally infected with Salmonella Enteritidis. Sixty-one day old chicks were grouped into three treatments, with two replicates, and reared until 21 days. Birds in the yacon group received 100mg of inulin/day orally for three consecutive days. On the seventh day of life the treated birds and the positive control were challenged orally with a culture of S. Enteritidis. There were no differences between groups in live performance. The infectivity index of the chicks supplemented with yacon was lower until the sixth day after the challenge, but at the end of the experiment it was higher than the positive control. Data from this study show that the use of inulin during the first 3 days of life caused a reduction of intestinal colonization of chickens by Salmonella Enteritidis in the first week after challenge. Further studies are needed to determine the dose and the ideal time of treatment necessary for a longer protective effect.(AU)

Shiga toxin-producing Escherichia coli (STEC): Zoonotic risks associated with psittacine pet birds in home environments.

Psittacidae are frequently bred as pets worldwide, but little is known about the zoonotic risks of these animals. The objective of this study was to investigate the presence of Shiga toxin-producing Escherichia coli (STEC) in the feces of psittacine birds housed as pets. A total of 171 fecal samples (67 cockatiels, 59 budgerigars, and 45 agapornis) were cultured. Forty-two (E. coli) strains were identified, and the presence of the eae, stx1, and stx2 genes was determined using PCR. The antimicrobial resistance profiles of the STEC strains were determined using the disk diffusion method and phylogenetic analysis according to the new Clermont phylotyping method. Using these methods, 19.4% (8/42) of the STEC strains were determined to be positive for the eae and stx2 genes. The results revealed a STEC frequency of 4.6% in the birds (8/171), with a percentage of 8.47% in budgerigars (5/59), 4.47% in cockatiels (3/67), and 0% in agapornis (0/45). None of the STEC isolates belonged to the O157 serogroup. Most of the strains were classified as sensitive to the 18 antibiotics tested. None of the strains exhibited a multiresistance profile. In the phylogenetic analysis, two strains were classified as non-typeable, three were classified as B2, two were classified as F, and one was classified as Clade I. Seven of the eight STEC strains showed a clonal profile using AFLP. E. coli strains that are stx2(+) plus eae(+) are usually associated with severe human diseases such as hemorrhagic colitis and hemolytic-uremic syndrome. The STEC-positive results indicate the zoonotic risk of breeding psittacidae in home environments.

Virulence and antimicrobial resistance of Klebsiella pneumoniae isolated from passerine and psittacine birds.

Klebsiella pneumoniae is considered one of the most important Gram-negative opportunistic pathogens. The contact between humans and birds poses health risks to both. The aim of this study was to investigate the resistance and virulence of K. pneumoniae isolates from psittacines and passerines, seized from illegal trade in Brazil. We analysed 32 strains isolated from birds of the orders Psittaciformes and Passeriformes by polymerase chain reaction (PCR) for virulence factor genes. Antibiotic resistance was assessed by disk diffusion assay and PCR. The results indicated that fimH (100%), uge (96.8%), kfu (81.2%) and irp-2 (68.7%) were the most common virulence genes, followed by kpn (46.8%), K2 (43.7%), mrkD (34.3%) and iroN (15.6%). The combination of virulence genes resulted in a great diversity of genotypes and the heterogeneity of the strains is also confirmed in the analysis by amplified fragment length polymorphism. The susceptibility profiles of the K. pneumoniae showed 25% of multiple antibiotic resistance strains. We identified seven strains that presented non-extended spectrum beta lactamase blaSHV variants SHV-1 and SHV-11 and one strain positive to the blaTEM-1 gene. Plasmid-mediated quinolone resistance was present in 10 strains (10/32). The data obtained in this study reveal the pathogenic potential of this pathogen and highlight the need for surveillance and monitoring.

Avaliação da atividade anti-helmíntica de extratos brutos de plantas da Floresta Amazônica e Mata Atlântica brasileira sobre Haemonchus contortus / Evaluation of the anti-helminthic activity of crude extracts from the Brazilian Amazon and Mata Atlântica plants against Haemonchus contortus

No mundo todo, as verminoses são causa de considerável prejuízo econômico na criação de ovinos. As perdas estão relacionadas ao retardo na produção, custos com tratamentos profiláticos e, em casos extremos, à morte dos animais. O objetivo deste trabalho foi verificar a ação anti-helmíntica de extratos vegetais sobre nematoides como alternativa terapêutica no tratamento da verminose em ovinos. Extratos orgânicos e aquosos foram obtidos de plantas nativas da Floresta Amazônica e Mata Atlântica, e foram testados na concentração de 100µg/mL em ensaios de toxicidade in vitro contra ovos de Haemonchus contortus e de 200µg/mL contra suas larvas. Na concentração estabelecida, apresentaram significante atividade relacionada à inibição de eclosão de ovos; em particular, o extrato orgânico de folhas e frutos de Trichilia sp. e o extrato aquoso dos órgãos aéreos de Phyllanthus attenuatus. Os resultados in vitro sugerem que extratos aquosos e orgânicos dessas plantas podem oferecer novas alternativas de controle da verminose em ovinos a partir de produtos naturais...

Helminthosis play a crucial role in small ruminant production leading to enormous economic losses particularly in areas where extensive grazing is practiced. It causes a loss of production through mortality, weight loss, reduced milk and wool production. Haemonchus contortus is a highly pathogenic small ruminant helminthes parasite, which is capable of causing acute diseases and high mortality. Therefore, there is an urgent need to seek alternative or complementary solutions to the control of parasitic nematodes of ruminants. The tropical forests concentrate the highest biodiversity in the world, particularly those located in Brazil, whose species richness is estimated to account for 20% of the total world richness and little is known about the chemical and pharmacological potentialities of Brazilian tropical forests. In this work, organic and aqueous extracts were tested on eggs and in the larval development test on Haemonchus contortus. The organic extract obtained from leaves and fruits of Trichilia sp. and the aqueous extract obtained from the aerial organs of Phyllanthus attenuates showed significant activity related to the inhibition of H. contortus egg eclosion. In vitro results suggest that both extracts, as well as eleven other active extracts, can offer alternatives in sheep worm control...

Protective effect of creatine against 6-hydroxydopamine-induced cell death in human neuroblastoma SH-SY5Y cells: Involvement of intracellular signaling pathways.

The guanidine-like compound creatine exerts bioenergetic, antiexcitotoxic, antioxidant and neuroprotective properties; however, the intracellular mechanisms responsible for these effects are still not well established. The purpose of this study was to investigate the protective effect of creatine against 6-hydroxydopamine (6-OHDA)-induced cell death in neuroblastoma SH-SY5Y cells and the possible intracellular signaling pathways involved in such effect. Exposure of SH-SY5Y cells to 100-300µM of 6-OHDA for 24h caused a significant concentration-dependent cell death measured as a diminution of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) reduction and as an increase in the extracellular release of lactate dehydrogenase. SH-SY5Y cells incubated for 24 or 48h with creatine (10-5000µM) was not cytotoxic. However, pre and co-treatment with creatine (0.3-1000µM) for 24h reduced 6-OHDA-induced toxicity. The protective effect afforded by creatine against 6-OHDA-induced toxicity was reversed by inhibitors of different protein kinases, i.e. phosphatidylinositol-3 kinase (PI3K) (LY294002), Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) (KN-93), protein kinase A (H-89), mitogen-activated protein kinase kinase 1/2 (MEK1/2) (PD98059) and protein kinase C (PKC) (chelerythrine). Furthermore, creatine prevented the 6-OHDA-induced dephosphorylation of glycogen synthase kinase-3ß (GSK-3ß) at the serine 9 residue. In conclusion, the results of this study show that creatine can protect against 6-OHDA-induced toxicity and its protective mechanism is related to a signaling pathway that involves PI3K, PKC, PKA, CaMKII, MEK1/2 and GSK-3ß.

Antidepressant-like effect of ursolic acid isolated from Rosmarinus officinalis L. in mice: evidence for the involvement of the dopaminergic system.

Ursolic acid, a constituent from Rosmarinus officinalis, is a triterpenoid compound which has been extensively known for its anticancer and antioxidant properties. In the present study, we investigated the antidepressant-like effect of ursolic acid isolated from this plant in two predictive tests of antidepressant property, the tail suspension test (TST) and the forced swimming test (FST) in mice. Furthermore, the involvement of dopaminergic system in its antidepressant-like effect was investigated in the TST. Ursolic acid reduced the immobility time in the TST (0.01 and 0.1mg/kg, p.o.) and in the FST (10mg/kg, p.o.), similar to fluoxetine (10mg/kg, p.o.), imipramine (1mg/kg, p.o.) and bupropion (10mg/kg, p.o.). The effect of ursolic acid (0.1mg/kg, p.o.) in the TST was prevented by the pretreatment of mice with SCH23390 (0.05mg/kg, s.c., a dopamine D(1) receptor antagonist) and sulpiride (50mg/kg, i.p., a dopamine D(2) receptor antagonist). The administration of a sub-effective dose of ursolic acid (0.001mg/kg, p.o.) in combination with sub-effective doses of SKF38393 (0.1mg/kg, s.c., a dopamine D(1) receptor agonist), apomorphine (0.5µg/kg, i.p., a preferential dopamine D(2) receptor agonist) or bupropion (1mg/kg, i.p., a dual dopamine/noradrenaline reuptake inhibitor) reduced the immobility time in the TST as compared with either drug alone. Ursolic acid and dopaminergic agents alone or in combination did not cause significant alterations in the locomotor and exploratory activities. These results indicate that the antidepressant-like effect of ursolic acid in the TST is likely mediated by an interaction with the dopaminergic system, through the activation of dopamine D(1) and D(2) receptors.

Effects of layer thickness for SAW, PSAW, and HVPSAW devices.

Considerable efforts in recent SAW device design and development have been aimed at obtaining high frequency, low loss, and high performance. A large number of applications relate to cellular and mobile telephony, pagers, local area networks, cordless phones, global positioning systems (GPS), and security systems. Pseudo-SAW (PSAW) and high velocity PSAW (HVPSAW) have received great attention because of their high phase velocities and, therefore, the high frequencies of operation that these modes provide. In addition to high phase velocities, the pseudomodes must also present low propagation losses and considerably high electromechanical coupling coefficients to be considered for surface acoustic wave (SAW) devices. This paper verifies that the metallic layer thickness is a relevant SAW device parameter, which must be considered to achieve lower losses for high frequency, low loss SAW devices. Popular PSAW and HVPSAW material orientations, such as 64 degrees YX LiNbO3 (0 degree -26 degrees 0 degree), 36 degrees YX LiTaO3 (0 degree -54 degrees 0 degree), LiNbO3 (90 degrees 90 degrees 36 degrees), LiTaO3 (90 degrees 90 degrees 31 degrees), and Li2B4O7 (0 degree 47.3 degrees 90 degrees), are considered as examples. In addition to the reduced loss analysis and the dispersion analysis for the pseudo modes, the present work discusses the transitions with respect to the layer thickness from the PSAWs and HVPSAWs to the generalized SAWs (GSAWs) and Rayleigh (sagittal particle motion) modes. In addition to contributing to the knowledge of the pseudomodes behavior with layer thickness, this mode transition analysis enlightens the situation in which the losses in the pseudo modes go to zero because of the merging of the pseudo modes into the SAWs (GSAWs and Rayleigh). The fact that the SAWs are a continuation as a function of thickness for the pseudo modes may be conveniently used in the fabrication of low loss devices. In addition, the effects of heavy layer metals, such as gold, in reducing the layer thickness at which the pseudo modes merge to the SAWs are discussed. Numerical results are compared with experimental data available in the literature, and the present analysis elucidates experimentally observed higher order pseudo modes and values of layer thickness for which lower losses are achieved.

Investigation on recent quartz-like materials for SAW applications.

Recent progress in growing and characterizing quartz-like materials of the trigonal system class 32 has been reported by several groups. The promising perspective for bulk acoustic wave frequency control applications indicates the potentiality of employing these materials for SAW applications as well. This paper reports results of investigations focused on SAW orientations of langasite (LGS), gallium phosphate (GaPO(4)), and langanite (LGN), both singly and doubly rotated cuts. Among the characteristics explored, major attention is paid to the temperature coefficient of delay (TCD), the electromechanical coupling coefficient (K(2)), and the power flow angle (PFA). Contour graphs are plotted based on our calculated results and show the regions in space in which low TCD and high K(2 ) can be obtained; they also exhibit the associated PFA and phase velocity characteristics. The influence of different sets of material constants is addressed. The spatial investigation performed shows that there are promising orientation regions in these materials at which zero or reduced TCD (<10 ppm/ degrees C) and PFA are obtained. Additional attractive characteristics for SAW applications have been observed: values of K(2) a few times higher than the K(2) of quartz ST-X, thus finding applications in larger bandwidth devices; variation of the TCD with respect to temperature, which is comparable to the variation found for quartz ST-X and less than that for zero TCD Li (2)B(4)O(7) cuts like 45 degrees X-Z and (0 degrees 78 degrees 90 degrees ); and phase velocity values circa 13 to 26% smaller than the phase velocity of quartz ST-X thus allowing a reduction in size for intermediate frequency device applications.

Comparison of ritonavir in a first choice three drug regimen, after two nucleoside analogues and in saquinavir experienced patients

Ritonavir is a potent, orally bioavailable inhibitor of HIV-1 protease. Our investigatiors underlook a retrospective study to compare the effectiveness of ritonavir (600 mg twice daily) associated with 2 reverse transcriptase inhibitors (RTIs) in 38 patients in 3 situations. Group I - patients previously treated with 2 RTIs, Group II - treatment-naive patients, and Group III - patients previously treated with 2 RTIs and saquinavir. Routine hematological and biochemical studies, HIV-1 viremia, and CD4 lymphocyte counts were performed before and after ritonavir. In group I, the median of HIV-1 RNA plasma levels decreased from 4.8 to 3.4 log10 copies/mL, in Group II from 5.9 to 2.9 log10 copies/mL, and in Group III from 5.2 to 4.1 log10 copies/mL (p=0.003, p=0.002, respectively, Wilcoxon signed rank test). The median increases of CD4+ cells occurred as follows: in Group I from 173 to 282 cells/mm3, in Group II from 92 to 254 cell/mm3, and in Group III from 68 to 133 cell/mm3(p=0.002, p=0.008, p<0.001, respectively, Wilcoxon signed rank test) In group II the mean weight increased from 55.2+14.3 kg to 59.4+15.7 kg and, in Group III, from 62.2+10.5 kg to 67.5+12 kg (p=0.026, p=0.002, respectively, paired T test). Patients in Group I presented no weight gain. Mild reversible hypertriglyceridemia occurred in 6 of 38 patients. The results of this study showed that ritonavir is a good choice for treatment naive patients and as a sequential option, not only after 2 RTIs, but also after a 3 drug regimen with saquinavir.

Extended investigation on high velocity pseudo surface waves.

Recent communication equipment such as mobile and cellular phones, radio systems, pagers, LANs, have demanded high performance components. Among these components, the last generation of SAW filters and signal processing devices, presenting low loss, flexible frequency and phase response characteristics, control of spurious, and so forth, have played a major role in designing new equipment and redesigning existing systems. The highest frequency obtainable with SAW technology in practical devices is limited to a couple of GHz, usually due to restrictions in the fabrication process involved and SAW propagation characteristics. The pseudo-SAW and the shear horizontal mode, presenting phase velocities circa 40% superior than the SAW and low attenuation along certain directions, have permitted the construction of devices operating at higher frequencies. The high velocity pseudo-SAW, with phase velocities about 100% higher than the SAW and low attenuation in many materials along certain directions, extends the high operating limit of SAW devices even further. In this paper the major characteristics of this new type of wave are reviewed. Extended topics such as: the boundary function magnitude behavior, the relationship between the "growing tilted bulk-like partial waves" and the bulk slowness, the number of roots (uncoupling of modes), and the Poynting vector behavior with depth are explored, enlightening the solution and behavior of this new type of high velocity pseudo-SAW.

A network model for arbitrarily oriented IDT structures.

A network model approach for analyzing arbitrarily oriented short-circuited SAW grating structures is extended to include interdigital transducers (IDTs) that are also arbitrarily oriented. The IDT structure is divided into cells, each modelled by a sequence of mismatched transmission lines consisting of a metallized and unmetallized region. The model includes: the impedance difference between metallized and free regions, the reflection coefficient at the metallization upstep, the reflection coefficient at the downstep for a counterpropagating wave, all deduced from the Datta-Hunsinger perturbation formula; the velocity difference between the free and metallized regions obtained using SAW propagation calculation software for arbitrarily oriented multilayers; and the energy storage susceptance at each finger discontinuity. Since only ordinary network elements are combined in accordance with the IDT geometry, this model permits good physical insight into the structure's characteristics and allows simple procedures for finding high directivity orientations.

Arbitrarily oriented SAW gratings: network model and the coupling-of-modes description.

A network model for surface-acoustic-wave (SAW) structures fabricated along arbitrary and hence nonsymmetric orientations, including natural single-phase unidirectional transducer (NSPUDT) directions, is described. From the predictions of this model for SAW gratings. the frequently used coupling of modes (COM) phenomenological description is evaluated. The network model consists of the usual sequence of mismatched transmission lines with susceptance loading at discontinuities to account for energy storage, plus a new additional reactive element calculated using a perturbation formula, to account for the asymmetry that exists for arbitrary orientations. The circuit elements are determined by geometrical and material parameters. It is demonstrated that the incremental COM description can be derived from the unit-cell-based network model, and analytical formulas quoted in the literature for the COM coefficients are compared with the values calculated from the ABCD network model description. An analytically tractable approximation for the network model is also described, from which rather simple explicit formulas for the COM coefficients that predict their dependence on material parameters and on frequency are derived. The analysis and numerical calculations indicate that these formulas may yield results that are valid over almost 30% relative bandwidths.

Intoxicacao aguda por sulfona - um caso de metemoglobinemia. / Acute poisoning induced by sulfones - a case of methemoglobinemia

Um caso de metemoglobinemia e descrito. A fisiopatologia e os aspectos clinicos sao discutidos sumariamente. Os principais mecanismos de reducao da molecula de hemoglobina sao igualmente referidos. A paciente apresentou cianose refrataria a oxigenioterapia, sendo tratada com 70 mg de azul de metileno e l% IV Constatou-se ainda ictericia hemolitica e colestatica. A agranulocitose nao esteve presente. A paciente recebeu alta hospitalar em boas condicoes