[Show abstract][Hide abstract] ABSTRACT: Montelukast is a selective and competitive cysteinyl leukotriene receptor antagonist (CystLTRA) which is increasingly used for the treatment of allergic asthma. Recently, hepatotoxicity has been reported with this drug in adult patients, but only one letter to the editor has reported a case of probable montelukast-induced hepatotoxicity in a child. We present a case of a 3.5-year-old boy, receiving treatment with montelukast, who developed hepatocellular injury. The exclusion of other causes of increased activity of aminotransferases (viral, metabolic, autoimmune), improvement after dechallenge, the morphological findings and previous reports of comparable cases support the diagnosis of montelukast-induced liver injury in this boy. Physicians should strictly analyse indications for this drug and be aware of potential drug-induced liver disease caused by this agent. Therefore, the periodical assessment of aminotransferases should be recommended during treatment with this leukotriene modifier.
[Show abstract][Hide abstract] ABSTRACT: Valproate (VPA) is a widely used antiepileptic drug. A serious neurological-outcome defined as valproate encephalopathy (VE) may rarely occur during VPA therapy. Structural abnormalities within neurons are postulated as one of the reasons for VE. The aim of this study was to assess the ultrastructure of neurons in the hippocampal cortex during the course of chronic application of VPA to rats. VPA was chronically administered to rats, intragastrically, once daily at a dose of 200 mg/kg b.w. for 1, 3, 6, 9 and 12 months. The samples of hippocampal cortex, after routine laboratory preparation, were examined by electron microscopy. The drug induced pronounced ultrastructural changes in the population of pyramidal neurons within the hippocampal cortex after 9 and 12 months of VPA administration. The most expressed abnormalities were observed within the mitochondria and manifested by fragmentation of crests and almost complete disappearance of intramitochondrial granules. Mitochondria of numerous neurons resembled large vacuolar structures. Widening, shortening and irregular distribution of rough endoplasmic reticulum was also found. A characteristic feature of damaged neurocytes in the last two phases of the experiment was the disintegration of nuclear chromatin and the presence of numerous lipofuscin deposits within hyaloplasm. These cells assumed the look of "dark neurons" and presented the ultrastructural features of apoptosis and necrosis. Our results indicate that long-term VPA administration to rats leads to aponecrosis of hippocampal neurons. (Folia Histochemica et Cytobiologica 2013, Vol. 51, No. 1, 31-37).
[Show abstract][Hide abstract] ABSTRACT: This study aimed to assess the pre-operative chemotherapy impact on the relationship between estrogen receptor (ER) expression and markers of proliferation and apoptosis in primary and metastatic breast cancer. Immunohistochemical examinations were conducted on surgically removed ductal invasive breast cancers and their lymph node metastases in 135 patients. A total of 64 patients from this group underwent pre-operative chemotherapy and in 71 cases the surgery was performed without primary chemotherapy. A negative correlation between ERα and Ki-67 was found in primary tumors and lymph node metastases. A positive correlation was observed between ERα and Bcl-2. A positive correlation was also noted between ERβ and Bak, suggesting that the two ERs were involved in the regulation of proteins responsible for the control of the apoptotic process. Assessment of the expression of the proteins conducted separately in primary tumors and lymph node metastases did not reveal a significant effect of pre-operative chemotherapy on the correlations of ERs with Ki-67, Bcl-2 and Bak. However, the analysis of the correlations between the receptor expression in primary tumors and Ki-67, Bcl-2 and Bak in lymph node metastases showed a statistically significant impact of pre-operative chemotherapy on the correlations of ERα and Bcl-2 with ERβ and Bak, confirming involvement of the two ERs in the regulation of apoptosis during breast carcinogenesis.
[Show abstract][Hide abstract] ABSTRACT: During carcinogenesis, loss of intracellular cohesion is observed among cancer cells with altered expression of such adhesion molecules as E-cadherin and beta-catenin, and aberrant expression and cellular location of intercellular gap junction proteins-connexins. The aim of this study was to evaluate immunohistochemically the expression and relationship between E-cadherin and beta-catenin, and the connexins Cx26 and Cx43 in 86 endometrioid adenocarcinomas. The aberrant cytoplasmic translocation of the studied proteins was a predominant finding, whereas only a minority of cases showed normal, nuclear beta-catenin labeling or membranous distribution of the remaining molecules. E-cadherin was positively and significantly associated with beta-catenin (P=0.001, r=0.366), as was Cx26 with Cx43 (P<0.001, r=0.719), E-cadherin with Cx26 (P<0.001, r=0.413), and E-cadherin and Cx43 (P<0.001, r=0.434) in all cancers. A subgroup of endometrioid adenocarcinomas (FIGO IB+II) exclusively showed a positive significant association between the expression of beta-catenin and Cx26 (P=0.038, r=0.339). In addition, there were significantly more beta-catenin-positive carcinomas among superficially spreading cancers (FIGO IA) than among deeper invading neoplasms (FIGO IB+II) (P=0.056). The altered location of the studied proteins indicates impairment of their physiological functions. In particular, normal membranous distribution of E-cadherin and connexins is lost and replaced by abnormal cytoplasmic accumulation in most cancers, and thus intercellular ties are expected to be weakened and loosened as a consequence. In contrast, the lack of relationship between beta-catenin and connexins, E-cadherin seems to be closely associated with the expression of Cx26 and Cx43 in endometrioid adenocarcinomas.
International journal of gynecological pathology: official journal of the International Society of Gynecological Pathologists 07/2010; 29(4):358-65. DOI:10.1097/PGP.0b013e3181c3c57f · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the study wad to estimate a potentially neuroprotective effect of topiramate (TPM) in the experimental model of FS.
24 young male rats divided in 4 groups were involved in the study. Febrile seizures were induced by placing the animals in 45 degrees C warm water bath for four consecutive days. TPM at the dose 80 mg/kg b.m. was administered: before the FS and immediately after the FS. FS group and control rats received only normal saline. Thereafter hippocampal slices were prepared to performing histological and morphometric examination.
Morphometric investigations revealed that FS caused death of 60% of the neurons in sector CA1 and a half of them in sector CA3. Histological examinations of hippocampal slices showed that TPM at a dose of 80 mg/kg b.m., administered before the seizures, considerably improved CA1 and CA3 pyramidal cell survival. Similar neuroprotective effect, but in a markedly lesser degree was observed when TPM was administrated after the FS.
Our findings seem to confirm that FS exert a strong destructive effect on the sensitive hippocampal neurons and on the neuroprotective properties of TPM in this process, which may have practical implications. It can be assumed that in children with recurrent and prolonged FS, prophylactic drug administration could prevent hippocampal sclerosis and development of symptomatic epilepsy.
Advances in Medical Sciences 02/2007; 52 Suppl 1(Suppl 1):161-5. · 1.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was evaluation the HBeAg/antiHBe seroconversion frequency as a result of lamivudine treatment in children who are nonresponders to previous IFN-alpha therapy.
The observation was carried out on 41 children, aged 4-17 years, with biopsy-proven chronic hepatitis B (HBeAg+) treated with lamivudine 3-4 mg/kg/d (max. 100 mg/d) for 12 months.
After 6 months of lamivudine therapy 59.3% children normalized GPT activity and only 1 child (2.5%) lost HBeAg. At the end of 12 months of therapy 81.5% normalized GPT activity and 4 of them (10%) lost HBeAg and seroconverted to antiHBe. None of treated children lost HBsAg. The age, sex, pretreatment GPT activity and active histological disease were not predictors of lamivudine-induced HBeAg loss. There were no side effects of lamivudine therapy except one boy who had severe thrombocytopenia.
The HBeAg/antiHBe seroconversion rate after one year trial of lamivudine in children with chronic hepatitis B unresponsive to previous IFN alpha therapy was 10%. The age, sex, pretreatment GPT activity and active histologic disease were not predictors of lamivudine-induced HBeAg loss.
Polski merkuriusz lekarski: organ Polskiego Towarzystwa Lekarskiego 07/2004; 16(96):557-9.
[Show abstract][Hide abstract] ABSTRACT: S-100 is a structural protein of the central nervous system. An elevated level of S-100 in CSF is generally considered to be a marker of nervous tissue damage. The presence of this protein in blood serum points to the functional and/or morphological disruption of the blood-brain barrier. We measured S-100 in the cerebrospinal fluid and blood of children with two of the most often observed pathological states in child neurology--internal hydrocephalus and epilepsy. High levels of S-100 in CSF were detectable in children with internal hydrocephalus. Increased blood levels of S-100 protein were detectable in both groups of paediatric patients. Our preliminary results indicate neuronal damage in internal hydrocephalus and morphological and/or functional disturbances of the blood-brain barrier (their increased permeability) in both above mentioned disabilities.
[Show abstract][Hide abstract] ABSTRACT: Gap junctional intercellular communication (GJIC) is a mechanism for direct cell-to-cell signalling and is mediated by gap junctions (GJs), which consist of proteins called connexins (Cxs). GJIC plays a critical role in tissue development and differentiation and is important in maintenance of tissue homeostasis. The purpose of the study was to evaluate the expression of Cx26, Cx32 and Cx43 in the human colon. Surgical specimens were obtained from patients who underwent surgical resection of colorectal tumours. Tissue samples (50 cases) were collected from normal colon, at the maximum distance from the tumor. Using antibodies for Cx26, Cx32 and Cx43, immunohistochemical detection was made. In epithelial cells, strong Cx26 immunoreactivity was found, whereas Cx32 and Cx43 were sparsely distributed. Strong Cx43 immunostaining in muscularis mucosae was observed. In the circular layer of muscularis externa, expression of Cx43 and Cx26 was seen, but only in the portion closest to the submucosa. No immunoreactivity was found in the longitudinal muscle layer. Small vessels stained positively only for Cx43. Furthermore, there was no difference in staining between samples derived from various sections of the colon. This study showed immunohistochemically for the first time the expression of Cx26 in human colon mucosa.
Folia Histochemica et Cytobiologica 02/2004; 42(4):203-7. · 1.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to evaluate the correlation of c-erb-b2 and Bcl-xl expression in biopsy specimens of Barrett's oesophagus from 44 patients with morphological features. The examined group was subdivided into: negative for dysplasia, indefinite for dysplasia, positive for dysplasia-low grade, and adenocarcinoma with high grade dysplasia. Positive c-erb-B2 staining was found in 34.1% and Bcl-xl protein expression was observed in 96.9% of BE. The results showed increased c-erb-B2 and Bcl-xl protein expressions with progressive grades of dysplasia to adenocarcinoma. In conclusion, an evaluation of c-erb-B2 and Bcl-xl expression can be useful for the histopatologic diagnosis of BE and correct interpretation of dysplasia.
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to evaluate if measurement of TGF-beta1 has clinical usefulness as a marker of liver fibrosis using ROC analysis and to assess its serum concentration during IFN alpha treatment.
Fibrosis stage and inflammation grade were assessed according to Batts and Ludwig and Ishak et al. before and 12 months after the end of IFN alpha treatment of 30 children with chronic hepatitis B. TGF-beta1 was measured by means of the quantitative sandwich enzyme immunoassay technique using recombinant human TGF-beta soluble receptor type II as a solid phase pre-coated onto a microplate (R&D System Inc., Minneapolis, USA).
There was no significant correlation between serum TGF-beta1 level and the stage of liver fibrosis. However TGF-beta1 levels in patients before IFN alpha therapy were significantly higher than in controls. IFN alpha treatment did not improve histological fibrosis during 18 months of observation and it did not cause any significant changes in serum TGF-beta1 levels although there was a tendency to decrease its level during therapy and follow-up.
Serum concentration of TGF-beta1 does not predict advanced liver fibrosis in children with chronic hepatitis B.
[Show abstract][Hide abstract] ABSTRACT: Morphometric analysis of the cerebellar cortex capillary cross-section area performed in experimental valproate encephalopathy using transmission electron microscopy showed that prolongation of VPA application resulted in more enhanced lumen narrowing manifested in gradual reduction in the mean value of the coefficient examined. After 6, 9 and 12 months of experiment this value was statistically different from that obtained in control subgroups, being respectively lower by approximately 22%, 48% and 65%. One month after terminating of chronic administration this value was close to the one found after 12 months of the study. Three months after the drug withdrawal the coefficient was higher by approximately 44% compared to the one after 12 months, which seemed to indicate an increase in capillary lumen patency. The morphometric analysis of the cerebellar cortex capillary cross-section area performed in the present study objectifies the results of qualitative ultrastructural investigations concerning the microcirculation of this CNS structure.
[Show abstract][Hide abstract] ABSTRACT: CD44 is a cell adhesion molecule involved in tumour growth and progression. This study was undertaken to evaluate the expression of CD44 standard protein in a series of 54 colorectal adenocarcinomas in correlation with cathepsin D immunoreactivity and some other clinicopathological variables. Formalin-fixed and paraffin-embedded tissues were investigated with anti-CD44 standard protein and anti-cathepsin D antibody. Immunolocalisation of CD44 protein and cathepsin D was performed using LSAB method. 13 (41.9%) out of 31 carcinomas without lymph-node metastases had positive CD44 expression, whereas only 6 (26.1%) out of 23 carcinomas with lymph-node metastases were found positive for CD44 expression. CD44 expression in carcinomas was positively correlated with tumour cells cathepsin D (p<0.01) immunostaining. statistically significant correlation was found between the expression of CD44 standard protein and the tumour site, age and sex of the patients. These results suggest that the standard-type CD44 protein lymph-node metastases, probably with cooperation of cathepsin D.
[Show abstract][Hide abstract] ABSTRACT: The review of literature concerning gastritis, especially the chronic form has been carried out. Based on published data and own authors experience an application of the Sydney System in differential diagnosis of gastritis was presented.
[Show abstract][Hide abstract] ABSTRACT: The effect of cyclophosphamide (CP) on the ultrastructure of the lung tissue and the activity of angiotensin converting enzyme (ACE) in serum was evaluated in rats. The animals were given cyclophosphamide (CP) in a single intraperitoneal dose of 150 mg/kg b.w. ACE activity was evaluated in the blood serum collected from the left ventricle of the heart using the spectrophometric method. In all time subgroups, the CP-receiving animals showed a decrease in ACE activity. Ultrastructural examinations of CP-treated animals revealed increased adhesion of neutrophiles and monocytes to the damage endothelium of the alveolar septa vessels and focally accumulation of the platelets.
[Show abstract][Hide abstract] ABSTRACT: Some cyclophosphamide toxic effects on lung tissue are presented. Cyclophosphamide metabolism, pathogenesis of lung damage and morphological lung tissue changes caused by that agent were characterized. Attention was focused on BAL evaluation as a useful method in the monitoring of lung tissue damage degree.