Diclofenac phonophoresis in human volunteers

A quantitative study of sodium diclofenac (Voltaren Emulgel, Novartis) phonophoresis was undertaken in humans. Fourteen healthy human volunteers were submitted to ultrasound irradiation on two 225-cm2 areas on the dorsum (group A), followed by the application of the medication gel, and the plasma diclofenac mass was measured at 1, 2 and 3 h later by high performance liquid chromatography. The same procedure was repeated one month later with the same volunteers but with the ultrasound equipment switched off for the control group (group B). The plasma diclofenac mass was significantly higher in group A than in group B at 1 h (0.0987 microg/mL as opposed to 0.0389 microg/mL; p=0.01) and 2 h (0.0724 microg/mL as opposed to 0.0529 microg/mL; p=0.01), but not at 3 h (0.0864 microg/mL as opposed to 0.0683 microg/mL; p=0.16). The authors conclude that previously applied therapeutic ultrasound irradiation enhances the percutaneous penetration of the topical diclofenac gel, although the mechanism remains unclear.     

Reticulocyte evaluation in alpha(+)-thalassemia

Although it is almost certain that alpha(+)-thalassemia protects against malaria, the mechanisms for that are still unknown. It has been suggested that an increased number of young circulating red blood cells in alpha(+)-thalassemic children, as a result of some degree of ineffective erythropoiesis, could be related to the high frequencies of the alpha(+)-thalassemic allele in malaria endemic areas. Reticulocyte evaluation in this condition, however, has been poorly performed so far. Our objective was to determine the reticulocyte number and maturation degree, in addition to the soluble transferrin receptor and serum erythropoietin levels, in alpha(+)-thalassemia heterozygotes, comparing them with normal alpha-genotype controls. One hundred twenty-one alpha(+)-thalassemia carriers (-alpha(3.7)/alphaalpha) and 249 controls (alphaalpha/alphaalpha), all of them with normal serum ferritin levels, were subclassified according to age (1-5, 6-10, 11-15, 16-20, and over 20 years old). Reticulocyte analyzes were carried out by flow cytometry and sTfR and s-Epo levels determined by immunonephelometry and chemiluminescence, respectively. The comparisons did not show any significant difference between thalassemics and controls regarding the reticulocyte parameters [percentages and absolute values, P = 0.2643 and 0.5421; high, medium, and low maturation degree, P = 0.2579, 0.2196, and 0.4192; RET maturity index (RMI), P = 0.2471, respectively], as well as the s-Epo levels (P = 0.5711). The sTfR concentrations were higher in the thalassemic group (P = 0.0001), but statistical significance was due only to the 1-5 and over 20 subgroups (P = 0.0082 and 0.0436, respectively). The results found here are compatible with a compensated erythropoiesis and do not confirm the hypothesis mentioned above.     

Differential neuroprotection by A(1) receptor activation and A(2A) receptor inhibition following pilocarpine-induced status epilepticus

Aiming at a better understanding of the role of A(2A) in temporal lobe epilepsy (TLE), we characterized the effects of the A(2A) antagonist SCH58261 (7-(2-phenylethyl)-5-amino-2(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine) on seizures and neuroprotection in the pilocarpine model. The effects of SCH58261 were further analyzed in combination with the A(1) agonist R-Pia (R(-)-N(6)-(2)-phenylisopropyl adenosine). Eight groups were studied: pilocarpine (Pilo), SCH+Pilo, R-Pia+Pilo, R-Pia+SCH+Pilo, Saline, SCH+Saline, R-Pia+Saline, and R-Pia+SCH+Saline. The administration of SCH58261, R-Pia, and R-Pia+SCH58261 prior to pilocarpine increased the latency to SE, and decreased either the incidence of or rate of mortality from SE compared with controls. Administration of R-Pia and R-Pia+SCH58261 prior to pilocarpine reduced the number of Fluoro-Jade B-stained cells in the hippocampus and piriform cortex when compared with control. This study showed that pretreatment with R-Pia and SCH58261 reduces seizure occurrence, although only R-Pia has neuroprotective properties. Further studies are needed to clarify the neuroprotective role of A(2A) in TLE.     

Synthesis and purification of the aflatoxin B1-lysine adduct

This work reports the chemical synthesis of aflatoxin B₁ (AFB₁)-lysine based on procedures available in the literature, but using lysine without a protection group in the α-amine group. AFB₁-exo-8,9-epoxide was obtained by epoxidation of AFB₁ with chloroperoxybenzoic acid in dichloromethane and phosphate buffer. Purification and identification of the AFB₁-lysine were conducted by liquid chromatography (LC), and its structure was confirmed by LC with mass spectrometer and diode-array detection. The preparation of AFB₁-lysine using lysine without a protection group in the α-amine group was completed in 24?h, being a practical modification of available methods that can be reproduced in analytical laboratories.     

Expanded Milan criteria on pathological examination after liver transplantation: analysis of preoperative data

BACKGROUND: We sought to evaluate the accuracy of imaging techniques related to the Milan criteria (MC) compared with the explant histology and the survival of these patients. METHODS: Between 1997 and 2006, we selected 45 cirrhotic patients with hepatocellular carcinoma distributed into two groups according to explant histology: MC and Expanded Milan Criteria (EMC). Age, gender, preoperative imaging (ultrasound [US] and/or computed tomography [CT]), maximal tumor dimension, number of tumors, explanted histology, histology degree, alpha-fetoprotein (AFP) level and vascular invasion were compared among the patients to evaluate the value of these prognostic factors for survival after liver transplantation. RESULTS: By histology 42.2% explants were identified as EMC. The mean AFP level was 204.5 ng/mL. Vascular invasion was detected in 31.5% of explants and 68.4% showed incidental tumors. The survival rates after 10 years were 47.4% whereas MC patients showed 57.77%. The mean AFP level among MC patients was 150.2 ng/mL with vascular invasion detected in 7.7% of explants, and 47.4% with incidental tumors. The overall sensitivity of the imaging techniques was 83.3% for CT and 75% for US. The specificity was 96% for CT and 80.1% for US. CONCLUSION: Scan examinations in the preoperative evaluation underestimated about 42.2% of tumors. Those patients had vascular invasion but the survival after 10 years was similar between the ECM and MC groups.     

A post-1990s assessment of strategic hospital alliances and their marketplace orientations: time to refocus

In past years, many SHAs formed in local urban markets to better compete for managed care contracts. In response to 1990s forces, these SHAs appear to have adapted product, production, and selling orientations to their markets, aimed at large institutional purchasers of health care. However, health care markets have evolved differently than anticipated. SHAs and their hospitals should now adopt the marketing orientation and focus more on patients and enrollees.     

Paternal selenium deficiency but not supplementation during preconception alters mammary gland development and 7,12‐dimethylbenz[a]anthracene‐induced mammary carcinogenesis in female rat offspring

Breast cancer is a global public health problem and accumulating evidence indicates early‐life exposures as relevant factors in the disease risk determination. Recent studies have shown that paternal nutrition can influence offspring health including breast cancer risk. Selenium is a micronutrient with essential role in central aspects of embryogenesis, male fertility and cancer and that has been extensively studied as a chemopreventive agent in several breast cancer experimental models. Thus, we designed an animal study to evaluate whether paternal selenium deficiency or supplementation during preconception could affect the female offspring mammary gland development and breast cancer susceptibility. Male Sprague‐Dawley rats were fed AIN93‐G diet containing 0.15 ppm (control diet), 0.05 ppm (deficient diet) or 1 ppm (supplemented diet) of selenium for 9 weeks and mated with control female rats. Mammary carcinogenesis was induced with 7,12‐dimethylbenz[a]anthracene (DMBA) in their female offspring. Paternal selenium deficiency increased the number of terminal end buds, epithelial elongation and cell proliferation in the mammary gland of the female rat offspring and these effects were associated with higher susceptibility to DMBA‐induced mammary tumors (increased incidence and higher grade tumors). On the other hand, paternal selenium supplementation did not influence any of these parameters. These results highlight the importance of father's nutrition including selenium status as a relevant factor affecting daughter's breast cancer risk and paternal preconception as a potential developmental stage to start disease preventive strategies.     

The A1 receptor agonist R-Pia reduces the imbalance between cerebral glucose metabolism and blood flow during status epilepticus: Could this mechanism be involved with neuroprotection?

It is well known that the uncoupling between local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF), i.e. decrease in LCBF rates with high LCGU, is frequently associated with seizure-induced neuronal damage. This study was performed to assess if the neuroprotective effect of the adenosinergic A₁ receptor agonist R-N-phenylisopropyladenosine (R-Pia) injected prior to pilocarpine is able to reduce the uncoupling between LCGU and LCBF during status epilepticus (SE). Four groups of rats were studied: Saline, Pilo, R-Pia + Saline and R-Pia + Pilo. For LCGU and LCBF studies, rats were subjected to autoradiography using [¹⁴C]-2-deoxyglucose and [¹⁴C]-iodoantypirine, respectively. Radioligands were injected 4 h after SE onset. Neuronal loss was evaluated by Fluorojade-B (FJB) at two time points after SE onset (24 h and 7 days). The results showed a significant increase in LCGU in almost all brain regions studied in the Pilo and R-Pia + Pilo groups compared to controls. However, in R-Pia pretreated rats, the uncoupling between LCGU and LCBF was moderated in a limited number of structures as substantia nigra pars reticulata and hippocampal formation rather in favor of hyperperfusion. Significant increases in LCBF were observed in the entorhinal cortex, thalamic nuclei, mammillary body, red nucleus, zona incerta, pontine nucleus and visual cortex. The neuroprotective effect of R-Pia assessed by FJB showed a lower density of degenerating cells in the hippocampal formation, piriform cortex and basolateral amygdala. In conclusion our data shows that the neuroprotective effect of R-Pia was accompanied by a compensatory metabolic input in brain areas involved with seizures generation.