HLA markers in familial Lichen Sclerosus

Background: Lichen sclerosus (LS) has been identified with increased frequency in families,often associated with HLA markers, mainly DQ7. A genetic co‐etiology seems likely in this setting. Moreover, there is an association of LS with autoimmune disorders, such as the presence of anti‐thyroid peroxidase autoantibodies (anti‐TPO), a hallmark of autoimmune thyroid diseases. Patients and Methods: In 3 families affected by LS, we verified their HLA markers, and identified previously undiagnosed cases of LS and autoimmune disorders. 30 individuals were examined with history, skin biopsy, HLA class I and II typing by PCR‐SSP, and measurement of anti‐TPO, free thyroxine and thyroidstimulating hormones (TSH) levels. Results: There were 8 cases of LS, 50 % of them anti‐TPO+. Autoimmune disorders were found in 40 % (total) and in 87.5 % of those affected. Most common HLA markers were B*15, B*57, CW*03, CW*07, CW*18, DRB1*04, DRB1*07, DRB4*. The three latter have been previously associated with LS. Conclusion: New cases of LS and autoimmune disorders can be detected in first degree relatives of patients with LS. The presence of anti‐TPO antibodies strongly suggests autoimmune thyroiditis. There is intra‐familial association between the haplotype HLA‐B*15 ‐DRB1*04 ‐DRB4* and anti‐TPO,emphasizing their link with thyroiditis. New familial approaches might help to make clear the pathogenesis of LS and its association with autoimmune diseases.     

Peripheral-type benzodiazepine receptor (PBR) gene amplification in MDA-MB-231 aggressive breast cancer cells

Recent studies using human breast cancer cell lines, animal models, and human tissue biopsies have suggested a close correlation between the expression of the peripheral-type benzodiazepine receptor (PBR) and the progression of breast cancer. This study investigates the genetic status of the PBR gene in two human breast cancer cell lines: MDA-MB-231 cells, which are an aggressive breast cancer cell line that contains high levels of PBR, and MCF-7 cells, which are a nonaggressive cell line that contains low levels of PBR. Both DNA (Southern) blot and fluorescence in situ hybridization analyses indicate that the PBR gene is amplified in MDA-MB-231 relative to MCF-7 cells. These data suggest that PBR gene amplification may be an important indicator of breast cancer progression.     

Loss of heterozygosity in normal breast epithelial tissue and benign breast lesions in BRCA1/2 carriers with breast cancer

Loss of heterozygosity (LOH) of the wild-type BRCA1/2 allele is a reproducible event in breast tumors of BRCA1/2 mutation carriers, but it is unknown if this allelic loss occurs only in association with recognizable histopathologic abnormalities. We evaluated the early genomic changes that occur in the mammary glands of patients with increased predisposition to breast cancer due to germline mutations in the BRCA1/2 genes. We tested the hypothesis that these genomic changes may be detected, not only in histologically abnormal and malignant breast tissues, but also in morphologically normal tissues and in areas with pathologically benign changes. Samples were obtained from five breast cancer patients: four BRCA1 carriers and one BRCA2 carrier. In each case, nontumor tissue areas surrounding the tumor or from other locations of the breast were isolated using laser capture microdissection. We evaluated 29 areas showing normal terminal ductal lobular units (TDLUs) or histopathologically benign changes (in particular, sclerosing adenosis), using a panel of polymorphic dinucleotide microsatellite markers for the BRCA1 gene and other chromosome 17 loci, for the BRCA2 gene and other chromosome 13 loci, and for the FHIT gene on 3p14.2. Overall, we analyzed a total of 105 samples of nontumor tissues; LOH was detected in 59 of the 105 (56%). In the normal TDLUs, 15 of 30 samples (50%) showed LOH; in the tissues with benign proliferative changes, such as sclerosing adenosis, 44 of 75 samples showed LOH (59%). Our results suggest that there is a field effect of early genetic events preceding morphologic changes in the mammary glands of BRCA mutation carriers.     

Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients

In this study we have investigated a group of 29 Brazilian patients, who had been diagnosed with the lysosomal storage disorder, Mucopolysaccharidosis type I (MPS-I). MPS I is caused by a deficiency in the lysosomal hydrolase, alpha-L-iduronidase. Ninety percent of the MPS I patients in this study were genotyped and revealed 10 recurrent and thirteen novel IDUA gene mutations. Eight of these new mutations and three common mutations W402X, P533R, and R383H were individually expressed in CHO-K1 cells and analyzed for alpha-L-iduronidase protein and enzyme activity. A correlation was observed between the MPS I patient clinical phenotype and the associated mutant alpha-L-iduronidase protein/enzyme activity expressed in CHO-K1 cells. This was the first time that Brazilian MPS I patients had been thoroughly analyzed and highlighted the difficulties of mutation screening and clinical phenotype assessment in populations with high numbers of unique mutations.     

Antimicrobial photodynamic therapy against Propionibacterium acnes biofilms using hypericin (Hypericum perforatum) photosensitizer: in vitro study

Lasers in Medical Science - Acne vulgaris is the most recurring skin condition in the world, causing great harm to the physical and psychological well-being of many patients. Antimicrobial...     

Effects of acute administration of the hydroalcoholic extract of mate tea leaves (Ilex paraguariensis) in animal models of learning and memory

Aim of the study

Ilex paraguariensis St. Hilaire (Aquifoliaceae) is a plant widely cultivated in South America that is used to prepare a tea-like beverage with a reputation to improve cognitive function, a response that has been attributed to the constituents of the leaves, especially caffeine. Our previous study indicated that the hydroalcoholic extract of Ilex paraguariensis presents an antiparkinsonian profile in reserpine- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-treated rodents.

Materials and methods

In the present study, the effects of the hydroalcoholic extract of Ilex paraguariensis on the short- and long-term learning and memory of rats were assessed with the social recognition, Morris water maze, and step-down inhibitory avoidance tasks.

Results

A preliminary HPLC fingerprint of the plant extract confirmed the presence of caffeine (the major compound), rutin and kaemperol, and revealed the absence of detectable concentrations of caffeic acid, quercetin and ursolic acid. Acute pre-training intraperitoneal (i.p.) or oral administration of the extract of Ilex paraguariensis improved the short-term social memory in a specific manner as well as facilitated the step-down inhibitory avoidance short-term memory evaluated 1.5 h after training. Moreover, a synergistic response was observed following the co-administration of ‘non-effective’ doses of caffeine and Ilex paraguariensis in the social memory. In contrast, pre-training administration of hydroalcoholic extract of Ilex paraguariensis did not alter the step-down inhibitory avoidance long-term memory evaluated 24 h after training, while the highest dose tested (250 mg/kg, i.p.) disrupted the animals’ performance in a cued version of the Morris water maze.

Conclusion

These results partly substantiate the traditional use of mate tea for improvement of cognition indicating that acute administration of hydroalcoholic extract of Ilex paraguariensis differentially modulates short- and long-term learning and memory in rats probably through its antagonist's action on adenosine receptors.     

Is it possible to stabilize the trunk using rhythmic stabilization in the upper limb? A cross-sectional study of asymptomatic individuals

Objective: The study aim was to evaluate the immediate effect of rhythmic stabilization on local and distant muscles involved in a functional reach. Method: Prospective, observational cross-sectional study. Eight right-handed and non-impaired individuals (4 females and 4 males) aged 18–24 years (21.5 ± 1.58 years) were evaluated. Bilateral electromyographic recording of the biceps brachii, triceps brachii, multifidus lumbar, and rectus abdominis muscles was performed during three different tasks. Task 1 involved functional reach, while Task 2 involved rhythmic stabilization followed by a functional reach. Task 3 was similar to Task 2, but with 3 repetitions before a functional reach. Results: The results showed no difference between the tasks or sides. However, an interaction was observed between each side and muscles, with greater activation of the right multifidus lumbar muscle. Conclusion: Rhythmic stabilization during the task of reaching promotes an increase of multifidus activity ipsilateral to its application. Thus, this particular technique of proprioceptive neuromuscular facilitation can be useful for improving stability of the trunk and can be used in clinical practice for this purpose. Level of Evidence: 5.     

Inhibition of the Mitochondrial Respiratory Chain by Alanine in Rat Cerebral Cortex

Alanine is a nutritionally nonessential amino acid synthesized by transamination of pyruvate originated from glucose. Alanine is the principal gluconeogenic amino acid because it can originate pyruvate and glucose through the inverse pathway. Considering that it has been suggested that alanine could be used as a dietary supplement in combination with growth hormone in the treatment of undernourished children affected by some inherited metabolic diseases to induce anabolism, the principal objective of the present work was to measure the activities of the mitochondrial respiratory chain complexes and succinate dehydrogenase in brain cortex of Wistar rats subjected to chronic alanine administration from the 6th to the 21st day of life. We also investigated the in vitro effect of alanine on the activities of mitochondrial respiratory chain complexes and succinate dehydrogenase in the same brain structure of 22-day-old rats. The results showed a reduction of Complex I + III and succinate dehydrogenase activities in brain cortex of rats subjected to alanine administration. We also verified that alanine inhibited the in vitro activity of Complexes I + III by competition with NADH. These results indicate that more investigation would be necessary before considering alanine supplementation as a valid adjuvant therapy to sick children with these disorders.