Endoscopic features in a model of multivisceral xenotransplantation

Introduction: Xenotransplantation and multivisceral transplantation are advanced therapeutic methods that still require a scientific basis. There are no experimental models of multivisceral transplantation available, particularly not the monitoring by endoscopy. Here, we describe the endoscopic features in a model of multivisceral xenotransplantation. Methods: The distal esophagus, stomach, intestine, colon, liver, pancreas, and the kidneys with a common vascular pedicle were harvested from rabbits and implanted in swine (group I, n = 9) or in rabbits (group II, n = 4). Endoscopy was performed in the stomach, jejunum, and ascending colon at four consecutive time points (immediate after surgery and 10, 90, and 180 min after reperfusion). Lesions were macroscopically graded as mild, moderate, and severe. Biopsies were taken following sacrifice at 180 min after reperfusion. Results: In group I, the stomach, jejunum, and colon manifested a progression of lesions with predominance of mild lesions after 10 min, mild to moderate lesions after 90 min, and moderate to severe lesions after 180 min. In animals from group II, endoscopy showed normal features at all time points after reperfusion. Histopathologic analysis confirmed the diagnosis of hyperacute rejection in group I. Grafts from group II animals presented normal or mild ischemic/reperfusion injury. Conclusion: All animals subjected to multivisceral xenotransplantation showed a progression of endoscopic lesions with time after transplantation, while animals subjected to allotransplantation showed no aberrations in endoscopy. We conclude that endoscopy is a useful tool in the assessment of hyperacute rejection of a xenograft.

Spatiotemporal solitons in multidimensional optical media with a quadratic nonlinearity

We consider solutions to the second-harmonic generation equations in two-and three-dimensional dispersive media in the form of solitons localized in space and time. As is known, collapse does not take place in these models, which is why the solitons may be stable. The general solution is obtained in an approximate analytical form by means of a variational approach, which also allows the stability of the solutions to be predicted. Then, we directly simulate the two-dimensional case, taking the initial configuration as suggested by the variational approximation. We thus demonstrate that spatiotemporal solitons indeed exist and are stable. Furthermore, they are not, in the general case, equivalent to the previously known cylindrical spatial solitons. Direct simulations generate solitons with some internal oscillations. However, these oscillations neither grow nor do they exhibit any significant radiative damping. Numerical solutions of the stationary version of the equations produce the same solitons in their unperturbed form, i.e., without internal oscillations. Strictly stable solitons exist only if the system has anomalous dispersion at both the fundamental harmonic and second harmonic (SH), including the case of zero dispersion at SH. Quasistationary solitons, decaying extremely slowly into radiation, are found in the presence of weak normal dispersion at the second-harmonic frequency.

Experimental multivisceral xenotransplantation

Background: Organ shortage impairs the proposition of multivisceral transplantation to treat multiple organ failure. Interspecies (xeno) transplantation is a valid solution for organ shortage; however, suitable models of this advance are lacking. We describe an effective model of multivisceral xenotransplantation to study hyperacute rejection. Methods: Under general anesthesia, we in block recovered the distal esophagus, stomach, small bowel, colon, liver, pancreas, spleen, and kidneys from donors and implanted heterotopically in the lower abdomen of recipients. Animals were divided into four groups: I-canine donor, swine recipient (n = 6); II - swine donor, canine recipient (n = 5); III-canine donor, canine recipient (n = 4); and IV-swine donor, swine recipient (n = 5). Groups I and 11 comprised experimental (xenotransplantation) and III and IV control groups (allotransplantation). During the experiment, we appraised recipient evolution and graft modification by sequential biopsy up to 3 h. At this time, we killed animals for autopsy (experimental end point). Results: We accomplished all experiments successfully. Every grafts attained customary appearance and convenient urine output immediately after unclamp. Around 15 min after reperfusion, xenografts achieved signs of progressive hyperacute rejection and absence of urine output. At the end of experiments we observed moderate to severe hyperacute rejection at small bowel, colon, mesenteric lymph node, liver, spleen, pancreas, and kidney, while stomach and esophagus achieved mild lesions. In contrast, allograft achieved normal or minimum ischemia/reperfusion injury and constant urine output. Conclusion: The present procedure assembles a simple and effective model to study multivisceral xenotransplantation and may ultimately spread researches toward hyperacute rejection.

Education Level Explains Differences in Stroke Incidence among City Districts in Joinville, Brazil: A Three-Year Population-Based Study

Background: Current evidence suggests an inverse association between socioeconomic status and stroke incidence. Our aim was to measure the variation in incidence among different city districts (CD) and their association with socioeconomic variables. Methods: We prospectively ascertained all possible stroke cases occurring in the city of Joinville during the period 2005-2007. We determined the incidence for each of the 38 CD, age-adjusted to the population of Joinville. By linear regression analysis, we correlated incidence data with mean years of education (MYE) and mean income per month (MIPM). Results: Of the 1,734 stroke cases registered, 1,034 were first-ever strokes. In the study period, the crude incidence in Joinville was 69.5 per 100,000 (95% confidence interval, 65.3-73.9). The stroke incidence among CD ranged from 37.5 (22.2-64.6) to 151.0 per 100,000 (69.0-286.6). The stroke incidence was inversely correlated with years of education (r = -0.532; p<0.001). MYE and MIPM were strongly related (R = 0.958), resulting in exclusion of MIPM by collinearity. Conclusions: Years of education can explain a wide incidence variation among CD. These results may be useful to guide the allocation of resources in primary prevention policies. Copyright (C) 2011 S. Karger AG, Basel

Chronic nasal instillation of residual-oil fly ash (ROFA) induces brain lipid peroxidation and behavioral changes in rats

Several epidemiological studies have linked particulate matter exposure to numerous adverse health effects on the respiratory, cardiovascular, and reproductive systems (Braga et al., 1999; Zanobetti et al., 2000; Anderson et al., 2001; Farhat et al., 2005). More recently, ambient levels of black carbon were associated to impaired cognitive function in children (Suglia et al., 2008), suggesting that the central nervous system (CNS) may be a target of air pollutants. The present study was conducted to (a) determine whether chronic residual oil fly ash (ROFA) exposure promotes behavioral changes and lipid peroxidation in rat brain areas, and (b) determine whether N-acetylcysteine (NAC), a general antioxidant, prevents these effects. Forty-five-day-old male Wistar rats were exposed or not to ROFA by intranasal instillation and were treated or not with NAC (150 mg/kg) ip for 30 days. One day later, rats were submitted to the open field test to evaluate the motor/exploratory activities and emotionality followed by decapitation. Striatum and cerebellum were dissected to determine lipid peroxidation by the accumulation of thiobarbituric acid-reactive substances (TBARS). ROFA instillation induced an increase in lipid peroxidation level in striatum (p = .033) and cerebellum (p = .030), as compared with the control group. NAC treatment blocked these changes. ROFA promoted a decrease in the frequency of peripheral walking (p = .006) and a decrease in exploration (p = .001), which were not blocked by N-acetylcysteine. The present study provides evidence that toxic particles, administered by the respiratory route, induce oxidative stress in structures of the central nervous system, as well as behavioral alterations. The administration of NAC reduces lipid peroxidation at the striatum and cerebellum levels, but does not influence behavioral disturbances.

Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men.

Background: Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition. Methods: We randomly assigned 2499 HIV-seronegative men or transgender women who have sex with men to receive a combination of two oral antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate (FTC-TDF), or placebo once daily. All subjects received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections. Results: The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at enrollment, and 100 became infected during follow-up (36 in the FTC-TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P=0.005). In the FTC-TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC-TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P=0.57). Conclusions: Oral FTC-TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT00458393.) N Engl J Med 2010;363:2587-99.

Photodynamic therapy for acne vulgaris: A critical review from basics to clinical practice Part II. Understanding parameters for acne treatment with photodynamic therapy

Photodynamic therapy requires a photosensitizer, oxygen, and activating light. For acne, pilosebaceous units are ""target"" structures. Porphyrins are synthesized in vivo from 5-aminolevulinic acid (ALA), particularly in pilosebaceous units. Different photosensitizers and drug delivery methods have been reported for acne treatment. There are a variety of porphyrin precursors with different pharmacokinetic properties. Among them, ALA and methyl-ester of ALA (MAT.) are available for possible off-label treatment of acne vulgaris. In addition, various light sources, light dosimetry, drug incubation time, and pre- and posttreatment care also change efficacy and side effects. None of these variables has been optimized for acne treatment, but a number of clinical trials provide helpful guidance. In this paper, we critically analyze clinical trials, case reports, and series of cases published through 2009. (J Am Acad Dermatol 2010;63:195-211.)

Clinical and biochemical studies in mucopolysaccharidosis type II carriers

The aim of the study was to characterize clinically and biochemically mucopolysaccharidosis type II (MPS II) heterozygotes. Fifty-two women at risk to be a carrier, with a mean age of 34.1 years (range 16-57 years), were evaluated through pedigree analysis, medical history, physical examination, measurement of iduronate sulfatase (IDS) activities in plasma and in leukocytes, quantification of glycosaminoglycans (GAGs) in urine, and analysis of the IDS gene. Eligibility criteria for the study also included being 16 years of age or older and being enrolled in a genetic counselling programme. The pedigree and DNA analyses allowed the identification of 40/52 carriers and 12/52 non-carriers. All women evaluated were clinically healthy, and their levels of urinary GAGs were within normal limits. Median plasma and leukocyte IDS activities found among carriers were significantly lower than the values found for non-carriers; there was, however, an overlap between carriers` and non-carriers` values. Our data suggests that MPS II carriers show lower plasma and leukocyte IDS activities but that this reduction is generally associated neither with changes in levels of urinary GAGs nor with the occurrence of clinical manifestations.