Hypercapnia prevents neovascularization via nitrative stress

Neovascularization after an ischemic insult is a beneficial attempt to salvage the injured tissue. Yet, despite the production of angiogenic factors within ischemic tissues, compensatory growth of new vessels fails to provide adequate vascularization. Thus, we hypothesized that local factors counter efficient revascularization. Whereas ischemia is often considered to be synonymous with an oxygen deficit, it is also associated with a concomitant local elevation of carbon dioxide (CO2). Although studies suggest that hypercapnia impacts tissue neovascularization, its significance relative to the abundantly described effects of hypoxia and its underlying mechanisms have yet to be elucidated. Therefore, we investigated the effects of hypercapnia on blood vessel growth in models of developmental and ischemic neovascularization. Acute and prolonged CO2 exposure inhibited developmental neovascularization of the rodent retina, as well as revascularization of the ischemic retina. Hypercapnia induced early increases in endothelial nitric oxide synthase and nitrative stress, associated with astrocyte impairment and endothelial cell death, as well as downregulation of the proangiogenic prostaglandin E2 receptor EP3. These results establish a previously unexplored means by which hypercapnia hinders efficient neovascularization, a mechanism that may contribute to ischemic tissue injury.     

植物细胞质外体多肽与蛋白研究

细胞质膜以外的质外体是植物细胞的重要组成部分, 质外体是植物细胞的重要信号源和细胞器。当植物遭受生物或非生物环境刺激时,可能首先引起质外体信号系统的变化; 同时质外体作为植物细胞之间最方便的通道, 在细胞间信号传递和信息交流上起重要作用, 从而成为协调植物细胞分化、器官形成和整体生长发育的决定性因素之一。本文概括地介绍了我室在此领域的一些研究进展。     

Immunocytochemical localization of 3-methylcrotonyl-CoA carboxylase in cultured ependymal, microglial and oligodendroglial cells

To evaluate the ability of ependymal, microglial and oligodendroglial cells to degrade leucine, the presence of 3-methylcrotonyl-CoA carboxylase (MCC) was investigated in cultures of these cells. MCC is a biotin-containing heterodimeric enzyme that is specific for the irreversible part of the leucine catabolic pathway. It has been reported previously that in cell culture MCC is expressed in astrocytes and a subpopulation of neurones. In the present study ependymal, microglial and oligodendroglial cell cultures, derived from the brains of newborn rats, were examined for the expression of MCC by RT-PCR, western blotting and immunocytochemistry. The results of RT-PCR and western blotting showed the presence of mRNA as well as protein of both subunits of MCC in ependymal, microglial and oligodendroglial cell cultures. Immunocytochemical investigation of the cellular and subcellular distribution of MCC demonstrated a mitochondrial location of MCC in all neuroglial cell types investigated. The ubiquitous expression of MCC in glial cells demonstrates the ability of the cells to engage in the catabolism of leucine transported into the brain, mainly for the generation of energy.     

The mitochondrial genome of stygobitic sponge Eunapius subterraneus: mtDNA is highly conserved in freshwater sponges

The complete mitochondrial DNA (mtDNA) genome of the Eunapius subterraneus (Porifera, Demospongiae), a unique stygobitic sponge, was analyzed and compared with previously published mitochondrial genomes from this group. The 24,850 bp long mtDNA genome is circular with the same gene composition as found in other metazoans. Intergenic regions (IGRs) comprise 24.7% of mtDNA and are abundant with direct and inverted repeats and palindromic elements as well as with open reading fames (ORFs) whose distribution and homology was compared with other available mt genomes with a special focus on freshwater sponges. Phylogenetic analyses based on concatenated amino acid sequences from 12 mt protein genes placed E. subterraneus in a well-supported monophyletic clade with the freshwater sponges, Ephydatia muelleri and Lubomirskia baicalensis. Our study showed high homology of mtDNA genomes among freshwater sponges, implying their recent split.     

Comparative proteomical and metalloproteomical analyses of human plasma from patients with laryngeal cancer

Laryngeal cancer is a significant disease worldwide, which presents an increasing incidence. Two contrasting ideas of the immune system role during cancer development are accepted: (1) it fights tumor cells, and (2) it aids tumor progression. Thus, there is no clear understanding about the immune response in laryngeal cancer. Furthermore, since tobacco is the main cause of laryngeal cancer and it contains various carcinogenic components, including metallic elements, these may play a role on cancer development. Plasmas of patients with laryngeal cancer and of healthy smokers were evaluated by 2D gel electrophoresis and mass spectrometry. Proteins were detected on every gel around pH 4.0–10.0 from molecular mass of 10–60 kDa. Few differences were found among cancer and control patients. However, three spots gathered between pI 7.3 and 7.6 with different molecular masses appeared exclusively in cancer profiles. From ten spots identified, six correspond to immune system components, including the three differential ones. The latter were observed only in cancer patients. The presence of several trace elements in the identified proteins was determined by inductively coupled plasma mass spectrometry, where chromium was increased in all proteins analyzed from patients with cancer. This study reinforces the importance of the immune response as target in the understanding and treatment of laryngeal cancer and the possibility that chromium is important in the carcinogenic progress.     

A case report of an unrecognized nevoid melanoma in a young woman--clinicopathological diagnostic challenge

Nevoid melanoma is a rare form of melanoma histologically resembling benign melanocytic nevi and may be overlooked in routine histological sections. Authors are presenting a case of a 31-year-old woman who presented with bizarre pigmented skin lesions in the area of the postoperative scar on the back where, 6 years earlier, a "nevus pigmentosus epidermo-dermalis" was excised and hystologically confirmed in outer institution. The lesions were surgically removed and histopathological findings were characteristic for nevoid melanoma. Additionally, specimen of primary removed lesion was reexamined and primary nevoid melanoma was then recognized, therefore indicating that the lesions our patient presented with are nevoid melanoma recidivisms. Extensive diagnostic procedures showed no signs of melanoma dissemination. Three months later, the patient returned for consultation and presented with two new brownish-pigmented papules in the area of the new postoperative scar. The lesions were excised and new nevoid melanoma recidivism was confirmed. The patient remained under the regular follow up and, almost 9 years after the removal of primary nevoid melanoma, followed by two cutaneous recidivisms, remains disease-free. This case aims to highlight the problematic area in the analysis of pigmented skin lesions where nevoid melanoma represents one of the clinical and pathological diagnostic challenges.     

Serum Vascular Endothelial Growth Factor (VEGF-C) as a Diagnostic and Prognostic Marker in Patients with Ovarian Cancer

VEGF-C is regarded as one of the most efficient factors in regulating lymphangiogenesis. The aim of this study was to better understand the role of VEGF-C in the progression of ovarian cancer and to assess its diagnostic and prognostic significance. A total of 109 patients with ovarian cancer, 76 patients with benign ovarian diseases, and 50 healthy controls were recruited in this study. Serum levels of VEGF-C were determined by ELISA method. The results showed that serum levels of VEGF-C were significantly higher in the patients with ovarian cancer than those with benign ovarian diseases and healthy controls (P<0.01). Serum level of VEGF-C was correlated with FIGO stage, lymph node metastasis, tumor resectability, and survival of the patients (P<0.05). The areas of receiver operating curves of VEGF-C were higher than those of CA125 in different screening groups. Analysis using the Kaplan-meier method indicated that patients with high VEGF-C had significantly shorter overall survival time than those with low VEGF-C (P<0.0001). In a multivariate analysis along with clinical prognostic parameters, serum VEGF-C was identified as an independent adverse prognostic variable for overall survival. These results indicated that serum VEGF-C may be a clinically useful indicator for diagnostic and prognostic evaluation in ovarian cancer patients.     

Dysplastic nevus--risk factor or disguise for melanoma

Dysplastic nevus is an acquired or hereditary nevus that clinically seems atypical and pathohistologically dysplastic. The term of dysplastic nevus has changed through history and even until now the dermatologists and pathologists have not found the same conclusion for name and definition of dysplastic nevus. Epidemiology of dysplastic nevus is different depending on geographic lattitude, being three times higher in Australia than in Great Britain. Genetic factors play a role in etiology of dysplastic nevus but are still not well defined. UV radiation is indisputable main etiological factor in developing dysplastic nevus. Many studies confirm that children who have been using sun protection creams with SPF have less dysplastic nevi than those who did not. Nevus with geographic shape and muddy borders, dominately macular, red to brown colored and has 5 mm or more in diameter is clinically dysplastic nevus. ABCDE rules count for dysplastic nevus as well as for melanoma but prefferable diagnostic criteria for dysplastic nevus would be "ugly duckling sign". Pathohistologic analysis is the key in confirming the diagnosis of dysplastic nevus. Great experience and knowledge in dermatopathology field is essential for pathologists to make a distinction between dysplastic nevus and melanoma in situ. Likewise great experience in dermatooncology field is essential in differentiating dysplastic nevus from other nevi. Surgical excision is the only therapy that should be done for dysplastic nevus. Regular follow up is highly recommended for patients with dysplastic nevus and syndroma naevi dysplastic. Education about sun protection measures and self-examination techniques is essential for all patients with dysplastic nevi and their family.     

Melasma--updated treatments

Melasma is a common, acquired facial skin disorder, mostly involving sun-exposed areas like cheeks, forehead and upper lip. Melasma occurs in both sexes, although almost 90 percent of the affected are women. It is more common in darker skin types (Fitzpatrick skin types IV to VI) especially Hispanics/Latinos, Asians and African-Americans. The onset of the melasma is at puberty or later, with exception of darker skin types, who tend to develop this problem in the first decade of life. The etiology is still unknown, although there are a number of triggering factors related to the onset of melasma. The most important are sun-exposure and genetic factors in both sexes, while hormonal activity has more important role in females. In addition, stress and some cosmetic products and drugs containing phototoxic agents can cause outbreaks of this condition. Melasma should be treated using monotherapies or combination of therapy, mainly fixed triple or dual combinations containing hydroquinone, tretinoin, corticosteroids or azelaic acid. Modified Kligman's formula is also very effective. Above mentioned therapy regimens in combination with UVA and UVB blocking sunscreens are mostly effective in epidermal melasma. Discontinuation of the use of birth control pills, scented cosmetic products, and phototoxic drugs coupled with UV protection are also benefitial in clearing of melasma. Alternative treatment including chemical peels and glicolic acid, seem to have the best result as a second line treatment after bleaching creams. Laser treatments show limited efficacy and should rarely be used in the treatment of melasma. Combining topical agents like hydroquinone, tretinoin and a corticosteroid in addition to sun avoidance, regular use of sunscreen throughout the year and patient education is the best treatment in this difficult to treat condition.