Determination of the cerebrovascular reserve capacity by using acetazolamide as well as transcranial Doppler and SPECT tests]

The aim of this study was the development of a simple bedside test to assess cerebrovascular reserve capacity using transcranial Doppler sonography. We tried to validate the increase in blood flow velocity as cerebrovascular reserve capacity in 20 (3 normal, 7 TIA, 10 completed stroke) patients. They were studied using transcranial Doppler sonography and rCBF SPECT before and after injection of 1 g acetazolamide. Their increases in blood flow velocity and changes in cerebral blood flow correlated significantly in the symptomatic hemispheres (p less than 0.001). Blood flow velocity between the two hemispheres (symptomatic and asymptomatic) was not significantly different at rest. We offer these simple and reliable methods in clinical studies to clarify the frequency of ischemic stroke of hemodynamic origin.     

Visualizing cytokine-secreting cells in situ in the rhesus macaque model of chronic gut inflammation

Cytokine-producing cells in gut-associated lymphoid tissues of rhesus macaques with chronic enterocolitis were studied. The confocal microscopy technique that we developed enables simultaneous in situ visualization of multiple extra- and/or intracellular antigens at a resolution higher than that allowed by light or epifluorescence microscopy. The presence of interleukin-6 (IL-6)-, tumor necrosis factor alpha (TNF-alpha)-, and IL-1-alpha-producing cells was focally intense in the colon lamina propria of the affected animals. The IL-1-alpha-producing cells were T lymphocytes (CD3+), while the TNF-alpha-producing cells were both macrophages (CD68+/HAM56+/LN5+) and T lymphocytes (CD3+). The IL-6-producing cells within the colon consisted of T lymphocytes and macrophages. The amount of IL-6-producing cells seen in macaques with enterocolitis was significantly higher (P<0.001) than that seen in the healthy control animal, while TNF-alpha- and IL-1-alpha-producing cells were seen only in macaques with enterocolitis. Most of the T lymphocytes that produced cytokines were detected in the lamina propria, while the macrophages were most prominent in highly inflamed regions of the lamina propria. Taken together, our findings indicate that there might be immunological similarity between chronic enterocolitis of rhesus macaques and humans, suggesting the potential use of the nonhuman primate model for the validation of novel therapies.     

Trypanosoma cruzi antigen that interacts with the beta1-adrenergic receptor and modifies myocardial contractile activity

Previously, we have demonstrated that plasma membranes from the parasite Trypanosoma cruzi (T. cruzi) recognize and adhere to host cells through parasite surface attachment molecules that have affinity for beta(1)-adrenergic receptors (beta(1)-ARs) on target organs. In this report we identify a parasite protein that not only interacts with beta(1)-ARs, but also displays beta-agonist-like activity. We demonstrate that a recombinant maltose binding protein fusion of Tc13 Tul (MBP-Tc13 Tul), a member of the T. cruzi antigen 13 family of surface antigen proteins, competes for binding sites with the beta-adrenergic receptor antagonist [125I]-CYP on membranes purified both from CHO cells expressing human beta(1)-ARs and from rat atria. The competition is prevented by pre-treating MBP-Tc13 Tul with antibodies directed against the EPKSA repeat domain of Tc13 Tul, implicating this portion of the molecule in binding to the beta(1)-AR. Furthermore, MBP-Tc13 Tul activates rat myocardial beta(1)-ARs, resulting in synthesis of cyclic adenosine monophosphate (cAMP) and an increase in cardiac contractility. These biological effects are selectively suppressed by the beta(1)-AR antagonist atenolol, by a synthetic peptide corresponding to the second extracellular loop of the human beta(1)-AR, and by the anti-EPKSA repeat antibodies. These results imply that the Tc13 Tul cell-surface antigen of T. cruzi plays a central role in misregulating the beta(1)-AR following parasite infection, and may be a causative factor of dysautonomic syndrome described in Chagas' disease.     

Spermatocytic seminoma. A clinicopathological and immunohistochemical study of 7 cases

Spermatocytic seminoma is an uncommon tumor, representing less than 1% of the testicular tumors, occurring most often in old patients. We report 7 cases of this entity. The average age at presentation was 66 years. Tumors had a polymorphic appearance with small, intermediate and large cells, and "spireme" figures. They were pure, with no sarcomatous component. In all cases, the tumor was limited to the testis. In the peritumoral tissue, there was no intratubular germ cell proliferation, and no atrophic testis. Immunostaining was negative for all the classical antibodies tested (cytokeratins, PLAP, lymphoid markers), but all the cases expressed c-kit (100%). This membranous positivity was focal in 4 cases, very strong, and diffuse in the 3 others. Spermatocytic seminoma must be recognized, because its favorable evolution in absence of a sarcomatous component. Adequate treatment consists of orchidectomy alone. Positive staining for c-kit may be helpful for the diagnosis of spermatocytic seminoma.     

Implication of the GABA(B) receptor in gamma vinyl-GABA's inhibition of cocaine-induced increases in nucleus accumbens dopamine

Previously, we demonstrated that gamma vinyl-GABA (GVG, Vigabatrin) dose-dependently inhibits cocaine-induced increases in dopamine (DA) concentrations in both the rodent and primate brain. Furthermore, it abolishes cocaine self-administration and conditioned place preference, while having no effect on locomotor activity or drug delivery to the brain. In an effort to better understand the mechanisms underlying this inhibition, we examined the effect of the selective GABA(B) receptor antagonist SCH 50911 on the GVG-induced decrease in cocaine's elevation of extracellular DA concentrations in the nucleus accumbens (NACC). Cocaine administration alone (20 mg/kg i.p.) produced a 480% increase in extracellular NACC DA levels. GVG (300 mg/kg i.p.) significantly reduced this increase by 25% (P<0.01). In sharp contrast, extracellular DA levels increased to 550% after the sequential administration of SCH 50911 (3 mg/kg i.p.), GVG, and cocaine. This increase is significantly different than GVG and cocaine (P<0.05) but similar to cocaine alone. These results demonstrate that the GABA(B) antagonist SCH 50911 was able to completely abolish GVG's inhibition of cocaine-induced increases in DA in the NACC and implicates the GABA(B) receptor in the mechanism underlying this inhibition.     

Molar incisor hypomineralization in HIV‐infected children and adolescents

The objective was to determine the prevalence of molar incisor hypomineralization (MIH) among individuals between 7 and 15 years old infected or noninfected with human immunodeficiency virus (HIV). The study was conducted with 33 HIV‐infected individuals (study group; SG) and 66 non‐HIV‐infected schoolchildren (control group; CG), paired by gender and age. Data collection was based on medical records (SG), a questionnaire for caregivers and oral examination for diagnosis of MIH (European Academy of Pediatric Dentistry criteria) and caries (DMFT index and ICDAS). Data were analyzed with Mann‐Whitney, chi‐square, and Fisher's exact tests and logistic regression. In SG, MIH (45.5%) and caries (87.9%) had higher prevalence. MIH was associated with use of protease inhibitors in SG (OR: 2.14; 95% CI: 1.21 to 3.77) and incubator need in CG (OR: 2.80; 95% CI: 1.71 to 9.10). HIV‐infected patients had a higher prevalence of MIH and dental caries in the permanent dentition.     

Possible role of glial cells in the onset and progression of Lyme neuroborreliosis

Background  

Lyme neuroborreliosis (LNB) may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early LNB. This inflammatory context could potentiate glial and neuronal apoptosis.     

Contractile activity and prostacyclin generation in isolated coronary arteries from diabetic dogs

Summary The present study was aimed at determining the generation of prostacyclin (PGI₂)-like-material in coronary arteries from normal and diabetic (pancreatectomized) dogs as well as the contractile responses to prostacyclin of preparations from normal, diabetic and insulin-treated diabetic animals. PGI₂ produced a dose-dependent relaxation of coronary arteries from normal dogs. In contrast, those from diabetic animals were not relaxed; indeed, at low concentrations PGI₂ failed to evoke any effect but at higher ones it induced a distinct contraction. In arteries from diabetic animals treated with insulin, PGI₂ induced a biphasic contractile effect, which lay between that of normal controls and untreated diabetics. In addition the basal generation of PGI₂-like-material by coronary arteries was significantly higher in the diabetic (141±0.2 pg/mg, mean±SEM) than in normal dogs (59±0.2 pg/mg). The present experiments demonstrate that the generation of PGI₂-like-substance is significantly increased in coronary arteries from diabetic dogs, but the same vessels are unable to respond to added authentic PGI₂ with relaxation; on the contrary they react with a distinct positive contractile response.     

Valor predictivo de la infiltración por linfocitos T intraepiteliales (CD3) en el pronóstico del cáncer colorrectal resecado

Introduction

Colorectal cancer (CRC) can induce an anti-tumoral immune response mediated by T-lymphocytes, which express CD3.

Objectives

To analyze the prognostic value of tissue expression of intraepithelial CD3 (CD3I) both overall and in the early tumoral stages.

Methods

We revised 251 patients with resected CRC and favorable clinical course. CD3I expression was analyzed by immunohistochemistry. Multivariate analysis was used to analyze the variables independently associated with survival. We analyzed CD3I(+) expression in relation to survival and tumoral progression, both overall and in patients with pTNM(I-II) stage tumors. The sensitivity, specificity, positive and negative predictive values and diagnostic accuracy of CD3I expression were analyzed.

Results

A total of 25.9% of patients with CRC were CD3I(+). After a mean follow-up of 74 months, CD3I(+) expression showed a favorable prognostic value for survival in the multivariate analysis (p = 0.045). Survival curves and absence of tumoral progression were more favorable in CD3I(+) cases, both overall (p = 0.009 and p = 0.004, respectively), and in stages I-II (p = 0.029 and p = 0.015). The specificity and positive predictive value of CD3I(+) were as follows: Survival: overall: specificity =0.89; positive predictive value =0.91. Stage (I-II): specificity =0.94; positive predictive value =0.98. Absence of tumoral progression: overall: specificity = 0.89; positive predictive value =0.88. Stage (I-II): specificity =0.92; positive predictive value =0.96.

Conclusions

CD3I expression has an favorable independent prognostic value, with statistically significantly higher percentages of survival and absence of tumoral progression. This more favorable outcome is maintained in the less advanced stages (I-II). CD3I expression shows high specificity and positive predictive value.