Continuous Drugs Research Articles

RESISTÊNCIA LATERAL ÀS MACROLACTONAS EM NEMATODAS DE BOVINOS

No Rio Grande do Sul (RS), a bovinocultura de corte, em sua maioria, tem caráter extensivo e o controle parasitário é fundamentado no uso contínuo de drogas anti-helmínticas. Os produtos mais utilizados fazem parte do grupo das lactonas macrocíclicas (LM’s). No RS, já existem relatos da ocorrência de resistência a estes produtos em parasitas gastrintestinais. O objetivo deste trabalho foi determinar a eficácia de 10 LM´s disponíveis comercialmente em bovinos naturalmente infectados. Foram utilizados setenta bovinos da raça Nelore, de aproximadamente um ano de idade. Cada grupo (n=7) foi tratado com doramectina 1% (Dectomaxâ, Pfizer), moxidectina 1% (Cydectinâ, Fort Dodge), quatro ivermectinas 1% (Ivermectinaâ, Ouro Fino; Ivermectinaâ, Jofadel; Imectinâ, Irfa; Dectiverâ, Lapisa); ivermectina 3,1% (Ivomec Goldâ, Merial), duas abamectinas 1% (Abamectinaâ, Jofadel; Abactinâ, Biofarm), e a combinação de abamectina 1,25% com ivermectina 2,25% (Solutionâ, Intervet) na dose recomendada pelo fabricante. Amostras fecais foram colhidas nos dias 0, 7, 14 e 21 pós-tratamento para determinação do número de ovos e cultura de larvas e cálculo do percentual de eficácia com o programa estatístico RESO. A eficácia das drogas foi de 0, 0, 19, 89, 30, 13, 27, 0, 0, e 67% respectivamente, 21 dias pós-tratamento. Os gêneros, Trichostrongylus sp. e Cooperia sp. demonstraram resistência a todos os produtos. Embora nessa população de parasitas gastrintestinais o produto à base de ivermectina 3,1% e da combinação ivermectina e abamectina jamais tenha sido utilizado previamente, os dados obtidos confirmam o grave desenvolvimento da resistência lateral entre as LM’s nos mais importantes nematóides de bovinos.

IMMUNOMONITORING IN ALLOGRAFT RECIPIENTS TREATED WITH A TOLERANCE-ENHANCING IMMUNOSUPPRESSIVE REGIMEN

O147* Aims: Recipients of whole organ allografts were treated in accordance with two therapeutic principles of (1) recipient pretreatment with Thymoglobulin (THY, 3-6 mg/kg) or Campath (CAM, 30 mg) before graft reperfusion and (2) minimum posttransplant immunosuppression consistent with graft survival and function using tacrolimus monotherapy (target trough level of 10 ng/ml). Other agents (e.g. steroid, rapamycin) were added only to treat biopsy-proven rejection. This report described changes in immunological and hematological parameters with a minimum followup of >12 months. Methods: Blood samples were obtained at 1, 3, 6, and 12 months after transplantation for four-color flow cytometry of leukocyte lineages, in vitro cell proliferation assays, and ELISPOT using cadaveric donor splenocytes or live donor PBMC as alloantigens. Results: Pretreatment with THY or CAM resulted in significant posttransplant lymphocyte depletion, which slowly recovered over the next 6-12M. CAM had stronger and prolonged impacts on lymphocyte depletion. Recovery of CD4 population was slower than CD8, resulting in remarkably low CD4/CD8 ratios (<0.8) at 6-12M with a higher incidence in the CAM group. Likewise, DC1 and DC2 populations considerably decreased after transplantation. DC1 gradually recovered and became nearly normal by 12M (49% vs. 57% in normal volunteers); however, recovery of DC2 was remarkably slow, particularly in the CAM group, and was 5.5 ± 5.0% at 12M compared to 15.0 ± 9.0% in the normal. CAM, but not THY, also effectively depleted B cells, and significantly low B cell counts persisted for nearly 12M. At 1 year, 48 of 155 (31%) functioning kidney recipients were on daily immunosuppression with single or multiple drugs. The remaining 107 (69%) were on tacrolimus, cyclosporine, or rapamycin monotherapy, with doses spaced from one every other day to once weekly. Of 95 liver recipients, 26 (27%) are on daily therapy with single or multiple agents, while 69 (73%) are on spaced monotherapy. Detailed in vitro studies (MLR, CML, limiting dilution, ELISPOT) were performed in 20 kidney and 16 liver recipients with >1 year follow-up. Kidney recipients on continuous multiple drugs showed global suppression to mitogens and alloantigens. In contrast, two-thirds of recipients on spaced weaning showed donor-specific hyporeactivity with vigorous responses to mitogens and 3rd party alloantigens. The remaining recipients on spaced monotherapy had intact anti-donor reactivity by MLR; but, CML responses were low with CTLp frequencies of less than 1:90,000-300,000. Patients (n=2) with modest killing (10-16%) with CTLp of 1:60,000-150,000 showed a low frequency of γ-IFN positive cells in ELISPOT. On the contrary, although the majority of liver recipients were in more advanced stages of weaning, correlation between immunosuppression and in vitro results was less clear probably due to the complicated immunological status in this population (e.g. hepatitis). Approximately 50% showed donor-specific hyporeactivity or total suppression in MLR and CML. The remaining half showed reactivity to mitogens and alloantigens (donor and 3rd party) in MLR with a significantly higher background. Donor killing in CML was 8-43% with low CTLp frequencies of 1:<200,000. Conclusions: Donor-specific immune modulation was observed in a subset of allograft recipients pretreated with THY or CAM and given minimal posttransplant immunosuppression. In contrast, patients on continuous multiple drugs showed overall suppression.

Fomiversen sodium approved to treat CMV retinitis.

Nucleic acid-based therapy emerges as a powerful weapon for the treatment of tumors thanks to its direct, effective, and lasting therapeutic effect. Encouragingly, continuous nucleic acid-based drugs have been approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). Despite the tremendous progress, there are few nucleic acid-based drugs for brain tumors in clinic. The most challenging problems lie on the instability of nucleic acids, difficulty in traversing the biological barriers, and the off-target effect. Herein, nucleic acid-based therapy for brain tumor is summarized considering three aspects: (i) the therapeutic nucleic acids and their applications in clinical trials; (ii) the various administration routes for nucleic acid delivery and the respective advantages and drawbacks. (iii) the strategies and carriers for improving stability and targeting ability of nucleic acid drugs. This review provides thorough knowledge for the rational design of nucleic acid-based drugs against brain tumor.

Eradication of Helicobacter pylori did not accelerate the healing of gastric and duodenal ulcers /erosions in patients on long-term continuous nonsteroidal anti-inflammatory drugs

Eradication of Helicobacter pylori did not accelerate the healing of gastric and duodenal ulcers /erosions in patients on long-term continuous nonsteroidal anti-inflammatory drugs

Can eradication of Helicobacter pylori prevent future development of peptic ulcers in patients receiving long-term continuous nonsteroidal anti-inflammatory drugs

Can eradication of Helicobacter pylori prevent future development of peptic ulcers in patients receiving long-term continuous nonsteroidal anti-inflammatory drugs

Assessment of the Prognosis of Coronary Patients: Performance and Customization of Generic Severity Indexes

To assess the prognostic performance of general severity systems (APACHE II [acute physiology and chronic health evaluation], simplified acute physiology score [SAPS II], and mortality probability models [MPM II]) in coronary patients and to derive new customized indexes for coronary patients using a reduced number of variables. Inception cohort. Adult medical and surgical ICUs in 17 hospitals in Catalonia and the Balearic Islands. Four hundred fifty-six patients with acute myocardial infarction. The APACHE II, SAPS II, and MPM II variables and survival status at hospital discharge have been collected. Performance of the severity systems was assessed by evaluating calibration and discrimination. Logistic regression was used to customize the MPM II(24) and SAPS II indexes. Discrimination was high enough for all of the models. However, calibration of the MPM II(24) was not as satisfactory as for the other models. The MPM II(24) and SAPS II were both reduced to five variables (MPM II(24 cor:) age, PaO2, continuous vasoactive drugs, urinary output, and mechanical ventilation; SAPS II(cor:) age, PaO2/FI(O2) ratio, systolic BP, Glasgow coma score, and urinary output). Both models showed better calibration and discrimination than the original ones. Prognostic indexes developed for multidisciplinary patients show good performance when applied to patients with acute myocardial infarction, but customization can reduce the number of variables necessary to compute them without a loss of, and a possible improvement in, prognostic accuracy.

Testis-derived Sertoli cells survive and provide localized immunoprotection for xenografts in rat brain.

Transplantation of neural tissue into the mammalian central nervous system has become an alternative treatment for neurodegenerative disorders such as Parkinson's disease. Logistical and ethical problems in the clinical use of human fetal neural grafts as a source of dopamine for Parkinson's disease patients has hastened a search for successful ways to use animal dopaminergic cells for human transplantation. The present study demonstrates that transplanted testis-derived Sertoli cells into adult rat brains survive. Furthermore, when cotransplanted with bovine adrenal chromaffin cells (xenograft), Sertoli cells produce localized immunoprotection, suppress microglial response and allow the bovine cells to survive in the rat brain without continuous systemic immunosuppressive drugs. These novel features support Sertoli cells as a viable graft source for facilitating the use of xenotransplantation for Parkinson's disease and suggest their use as facilitators, (i.e., localized immunosuppression) for cell transplantation in general.

Reviews in Perinatal Medicine

are contributors) who cover a number of timely topics in perinatal medicine. For the introductory volume they scarcely could have found two more interesting or informative persons than Drs Lawrence Longo (with Gordon Power) and Abraham Rudolph to author the first two chapters on placental oxygen transfer and cardiac output in the mammalian fetus, respectively. The first volume also considers topics that include fetal pulmonary fluid, onset of breathing, pulmonary transition from fetal life, pulmonary structure during neonatal adaption, continuous transcutaneous oxygen measurements, drugs and anesthetics in the fetus, uterine pres¬ sure, maternal standing during the first stage of labor, betamimetic drugs, fetal heart rate, fetal breath¬ ing, fetal endocrinologie diagnosis, and prenatal genetic diagnosis. The second volume promises to cover a similarly wide group of topics. Most articles are relatively short, usually about 20 pages, although Dr Scarpel¬ li's article is about 68 pages long, Dr Cosmi's is 64, and Dr Carlo Valenti's discourse on genetic diagnosis is about 36 pages. In general, most of the articles are well written and almost all are on a high academic plane. However, here also is one of the problems—the majority of the articles are written for the academic community rather than for the broad community that includes also the practicing physicians. Many contributions tend to be a bit obscure even for the academician. An example of the excellent chap¬ ters that have appeal for all levels of endeavor is Cosmi's article on drugs and anesthetics in fetuses in which the pharmacological characteristics of these drugs are examined at a basic level, while the clinical significances are shown clearly. Also, Dr Eskes deals with uterine pressure at the most basic level, while presenting a beautiful exposition of clinical physi¬ ology of the contracting uterus. An¬ other example is the excellent chapter

Multiple hormonal responses to prolonged exercise in relation to physical training.

Multiple hormonal responses to prolonged exercise in relation to physical training.

Viable tubercle bacilli in closed lesions

‘Closed’ lesions in the resection specimens from 50 patients with ‘minimal’ pulmonary tuberculosis at the time of operation were sampled for direct examination, culture on Dubos and Löwenstein-Jensen media and injection into guineapigs. Eighty per cent of the cases had a positive smear in one or more samples. Thirty-eight per cent of the cases produced a positive culture and/or infection of guinea-pigs in one or more samples. Of the total 82 samples, 26 (31·7 per cent) produced ‘viable’ tubercle bacilli. The larger the sample the greater the chance of this happening. The influence of previous chemotherapy is discussed. Continuous drugs for less than six months still allowed for ‘viability’ in 12 out of 24 cases. Over six months, this figure was 7 out of 26 cases. Definite drug-resistance was found in only 2 out of all the positive cultures, in each case to one drug.