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The protective effect of montelukast sodium on carbon tetrachloride induced hepatopathy in rat

AIM This study investigates the effects of montelukast sodium (MK) (CysLTLT1 receptor antagonist) on CCl(4)induced hepatopathy on rat. MATERIAL AND METHODS We worked on 4 groups of 10 Wistar male rats each. The groups received as follows: group I (control group) - saline, group II - MK 5mg/kg/day i.p. for 5 days, group III - MK 5mg/kg/day i.p., 1 day prior to and 4 days concomitantly with CCl(4) p.o., 0.3ml/Kg/day and group IV - CCl(4), p.o., 0.3ml/Kg/day for 4 days. One day after the last administration, samples of blood were taken and alanine aminotransferase (ALT), total bilirubin (TB), direct bilirubin (DB), malondialdehyde (MDA), catalase (CAT) as well as total antioxidant capacity (TAC) were determined. The histopathological exam was performed. We also determined superoxide dismutase (SOD), MDA, CAT and GSH in liver homogenate. RESULTS Compared to group IV, group III exhibited statistically significant lower levels of ALT (318+/-15.75 versus 203.14+/-10.28 UI, p<0.0001), TB (3.16+/-0.30 versus 1.99+/-0.08mg/dl, p<0.0001), MDA in blood and in liver homogenate (4.98+/-1.71 versus 2.15+/-1.18nmol/ml, p=0.0004) and higher levels of SOD and CAT. Histopathologically, group IV presented important macro- and micro-vesicular hepatic steatosis and group III preserved lobular histoarchitecture and had less severe cellular lesions. CONCLUSION MK exhibits a partial hepatoprotective effect on rats treated with CCl(4).

Dental Pulp: Correspondences and Contradictions between Clinical and Histological Diagnosis

Dental pulp represents a specialized connective tissue enclosed by dentin and enamel, the most highly mineralized tissues of the body. Consequently, the direct examination as well as pathological evaluation of dental pulp is difficult. Within this anatomical context, our study aimed to evaluate the correlation between dental pulp lesions and clinical diagnosis. Pulpectomies were performed for 54 patients with acute and chronic irreversible pulpitides and for 5 patients (control group) with orthodontic extractions. The morphological features were semiquantitatively assessed by specific score values. The clinical and morphological correspondence was noted for 35 cases (68.62%), whereas inconsistency was recorded for 16 cases (31.38%). The results of the statistical analysis revealed the correlations between clinically and pathologically diagnosed acute/chronic pulpitides. No significant differences were established between the score values for inflammatory infiltrate intensity, collagen depositions, calcifications and necrosis, and acute, respectively chronic pulpitides. We also obtained significant differences between acute pulpitides and inflammatory infiltrate and calcifications and between chronic pulpitides and inflammatory infiltrate, collagen deposition, and calcifications. On the basis of the predominant pathological aspects, namely, acute and chronic pulpitis, we consider that the classification schemes can be simplified by adequately reducing the number of clinical entities.

Design and Testing of an Experimental Steam-Induced Burn Model in Rats

Background Most of the current models for experimental burns pose difficulties in ensuring consistency and standardization. Aim of Study We aimed to develop an automated, reproducible technique for experimental burns using steam-based heat transfer. Methods The system developed for steam exposure was based on a novel, integrated, computer-controlled design. Three groups of rats were exposed to steam for 1, 3, and 7 seconds. The lesions were evaluated after 20 minutes, 48 hours, and 72 hours after burn induction. Results One-second steam application produced a superficial second-degree burn; three-second application induced deep second-degree burn; and seven-second application led to a third-degree burn. Conclusion The high level of automation of our integrated, computer-controlled system makes the difference between our system and other models, by ensuring the control of the duration of exposure, temperature, and pressure and eliminating as many potential human generated errors as possible. The automated system can accurately reproduce specific types of burns, according to histological assessment. This model could generate the reproducible data needed in the study of burn pathology and in order to assess new treatments.

Lesser-Known Molecules in Ovarian Carcinogenesis.

Currently, the deciphering of the signaling pathways brings about new advances in the understanding of the pathogenic mechanism of ovarian carcinogenesis, which is based on the interaction of several molecules with different biochemical structure that, consequently, intervene in cell metabolism, through their role as regulators in proliferation, differentiation, and cell death. Given that the ensemble of biomarkers in OC includes more than 50 molecules the interest of the researchers focuses on the possible validation of each ones potential as prognosis markers and/or therapeutic targets. Within this framework, this review presents three protein molecules: ALCAM, c-FLIP, and caveolin, motivated by the perspectives provided through the current limited knowledge on their role in ovarian carcinogenesis and on their potential as prognosis factors. Their structural stability, once altered, triggers the initiation of the sequences characteristic for ovarian carcinogenesis, through their role as modulators for several signaling pathways, contributing to the disruption of cellular junctions, disturbance of pro-/antiapoptotic equilibrium, and alteration of transmission of the signals specific for the molecular pathways. For each molecule, the text is built as follows: (i) general remarks, (ii) structural details, and (iii) particularities in expression, from different tumors to landmarks in ovarian carcinoma.

Adipocytes spectrum — From homeostasia to obesity and its associated pathology

Firstly identified by anatomists, the fat tissue is nowadays an area of intense research due to increased global prevalence of obesity and its associated diseases. Histologically, there are four types of fat tissue cells which are currently recognized (white, brown, beige, and perivascular adipocytes). Therefore, in this study we are reviewing the most recent data regarding the origin, structure, and molecular mechanisms involved in the development of adipocytes. White adipocytes can store triglycerides as a consequence of lipogenesis, under the regulation of growth hormone or leptin and adiponectin, and release fatty acids resulted from lipolysis, under the regulation of the sympathetic nervous system, glucocorticoids, TNF-α, insulin, and natriuretic peptides. Brown adipocytes possess a mitochondrial transmembrane protein thermogenin or UCP1 which allows heat generation. Recently, thermogenic, UCP positive adipocytes have been identified in the subcutaneous white adipose tissue and have been named beige adipocytes. The nature of these cells is still controversial, as current theories are suggesting their origin either by transdifferentiation of white adipocytes, or by differentiation from an own precursor cell. Perivascular adipocytes surround most of the arteries, exhibiting a supportive role and being involved in the maintenance of intravascular temperature. Thoracic perivascular adipocytes resemble brown adipocytes, while abdominal ones are more similar to white adipocytes and, consequently, are involved in obesity-induced inflammatory reactions. The factors involved in the regulation of adipose stem cells differentiation may represent potential pathways to inhibit or to divert adipogenesis. Several molecules, such as pro-adipogenic factors (FGF21, BMP7, BMP8b, and Cox-2), cell surface proteins or receptors (Asc-1, PAT2, P2RX5), and hypothalamic receptors (MC4R) have been identified as the most promising targets for the development of future therapies. Further investigations are necessary to complete the knowledge about adipose tissue and the development of a new generation of therapeutic tools based on molecular targets.

Complex Mechanisms of Matrix Metalloproteinases Involvement in Endometrial Physiology and Pathology—An Update

Matrix metalloproteinases (MMPs) belong to a multigenic family of proteolytic enzymes with great structural variability which provide a complex intervention in pathophysiological conditions. Our review is focused on both MMPs key role in physiological reproductive events, such as embryo implantation, uterine involution, normal endometrial cycle, and on their role in the main endometrial pathologies. MMPs activity is closely regulated by tissue inhibitors of MMPs (TIMPs). MMP: TIMP imbalance has been incriminated in various pathological conditions, including endometrial cancer and endometriosis. Accumulated data support the involvement of a large spectrum of MMPs and TIMPs in endometrial carcinogenesis. Strong MMP-2 and weak TIMP-2 tissue immunoexpressions have a powerful prognosis value, while MMP-9 high expression suggests its important involvement in endometrial tumor invasiveness. Endometriosis development implies an accumulation of events showing partial overlap with endometrial carcinogenesis and invasion, requiring MMPs involvement. Therefore, increased levels of several MMPs have been detected in peritoneal fluid and/or endometrial tissue of patients diagnosed with endometriosis. Endometriotic mesenchymal stem cells (MSCs) may be involved in the pathogenesis of endometriosis due to their upregulated expression for markers of migration and angiogenesis, such as MMP-2, MMP-3, MMP-9, and VEGF. The hypothesis of therapeutic benefits of synthetic MMPs inhibitors, added to the progesterone or progestins action, has been based on the complex MMPs involvement in endometrial pathology. Future research is necessary to elucidate the complex interactions between molecules involved in proliferation, angiogenesis and apoptosis, opening new perspectives in the early diagnosis and treatment of endometrial neoplasia and endometriosis.

Heterogeneous Periostin Expression in Different Histological Variants of Papillary Thyroid Carcinoma

Background Periostin (PN) epithelial and stromal overexpression in tumor pathology has been studied according to tumor growth, angiogenesis, invasiveness, and metastasis, but a limited number of studies address PN in thyroid tumors. Aim Our study aimed to analyze PN expression in different histological variants of PTC and to correlate its expression with the clinicopathological prognostic factors. Material and Methods PN expression has been immunohistochemically assessed in 50 cases of PTC (conventional, follicular, oncocytic, macrofollicular, and tall cell variants), in tumor epithelial cells and intratumoral stroma. The association between PN expression and clinicopathological characteristics has been evaluated. Results Our results show that PTC presented different patterns of PN immunoreaction, stromal PN being significantly associated with advanced tumor stage and extrathyroidal extension. No correlations were found between PN overexpression in tumor epithelial cells and clinicopathological features, except for specific histological variants, the highest risk of poor outcome being registered for the conventional subtype in comparison to the oncocytic type. Conclusions Our study demonstrates differences in PN expression in histological subtypes of PTC. Our results plead in favor of a dominant protumorigenic role of stromal PN, while the action of epithelial PN is less noticeable.

Comparative analysis of CD4 and CD8 lymphocytes — evidences for different distribution in primary and secondary liver tumors

INTRODUCTION The impact of tumor cells on tumor-infiltrating lymphocytes (TILs) in cancer development is not yet clarified. Our study analyzed the distribution and prognostic value of CD4+ and CD8+ T lymphocytes in hepatocellular carcinoma (HCC) and liver metastases (LM). MATERIAL AND METHODS Archival tissue specimens of 35 HCC and 39 LM patients were immunohistochemically processed. The number of intratumoral (IT) and peritumoral (PT) CD4+ and CD8+ T cells was quantitatively analyzed. RESULTS We noted large variances of T lymphocyte subpopulations. Similar number of CD4+ and CD8+ lym-phocytes was present in HCC, whereas in LM the number of CD8+ cells was approximately two times higher than CD4+ lymphocytes. A significant prevalence of T cells in PT over IT areas was observed. The prognostic value was demonstrated only for PT CD8+ lymphocytes in LM, their reduced number being associated with shorter survival. CONCLUSIONS The differences between proportions of T lymphocytes within tumor and its environment might be explained by proapoptotic effect of cancer cells on TILs.

Metalloproteinases involvement in liver tumoral pathology- an update

MMPs and TIMPs involvement in tissue destruction may be incriminated in malignant invasion and metastasis, showing correlations between the overexpression, aggressiveness, tumor stage and prognosis. Recent data provide evidence of their complex role in creating an auspicious microenvironment for tumor growth in primary and metastatic sites. The investigation of MMPs and TIMPs functional interdependency is an important direction, useful in carcinogenesis intrinsic mechanisms deciphering, its apparently paradoxical role being incompletely defined. Literature review regarding MMPs and TIMPs study in primary and secondary hepatic tumors allows us to affirm that defining a precise profile of their activities is extremely difficult. The most studied metalloproteinase, in liver tumoral microenvironment, were MMP2 and MMP9 together with their inhibitors TIMP 2 and TIMP1, respectively. The expression variability of both MMPs and TIMPs is associated to promoter or inhibitor action of stromal cells and / or tumor cells, as liver microenvironment has a modulatory action for MMPs and TIMPs. MMPs capacity to intervene in many biological processes is attributed to their ability of ECM proteolysis, as a possible initiator of unrevealed functions. The understanding of biochemical and structural aspects of MMPs, and the capacity to form molecular complexes with TIMPs open the perspectives of design of potent specific inhibitors for MMPs and, thus, the development of new therapies for primary and metastatic liver cancers.

Acute tacrolimus nephrotoxicity in kidney transplanted patients - from kidney biopsy to urinary markers of acute kidney injury: a case report

Calcineurin inhibitors (CNIs) play a major role in kidney transplant immunosuppressive regimens, but they also may cause acute and chronic kidney toxicity, which is an important cause of long-term graft failure if not recognized and treated promptly. Therapeutic approaches are different and sometimes even opposite in acute graft dysfunction, requiring detailed differential diagnosis. Current guidelines consider the renal biopsy to have the highest specificity and sensitivity in the diagnosis and correct therapy guidance of acute graft dysfunction. However, the renal biopsy is an invasive and expensive method that predisposes to complications. In the last decade, a number of studies were focused on the urinary levels of various biomarkers like kidney injury molecule-1 (KIM-1), neutrophil gelatinase associated lipocalin (NGAL), interferon induced protein-10 (IP-10) or cystatin C (CysC) as potentially valuable non-invasive methods of allograft pathology diagnosis. We report the case of a 27 year-old male who underwent a kidney transplant and for which the urinary measurement of these biomarkers proved extremely useful in diagnosing the acute tacrolimus nephrotoxicity, which further allowed a correct therapeutic approach.