Pattern of airway inflammation and remodeling in mild chronic obstructive pulmonary disease

Airway wall remodeling is present in the airways of patients with COPD and is considered the most important contributor to the airflow limitation. To study the airway structural abnormalities and the role of mast cells in mild COPD. Thirty patients having mild COPD were subjected to sputum analysis and fiberoptic bronchoscopic biopsies from the main and segmental bronchi. BAL was obtained from segmental bronchi. At the level of mucosa there was infiltration by macrophages, lymphocytes and few numbers of neutrophils. Congestion, epithelial shedding and squamous metaplasia were more prevalent than in the central airways. At level of the submucosa there was goblet cell hyperplasia in 70% of cases. The muscle layer had an increased thickness in 80% of cases in comparison to 56.7% in the central airways and 83.3% showed thick fibrosed wall and shed epithelium in comparison to 40.0% in central airway. The pathological hallmark of COPD was mainly at the level of the small airways both at the level of the cellular components of BAL and at the level of histopathology

Human telomerase reverse transcriptase [hTERT] gene expression in thyroid carcinoma: diagnostic and prognostic role

The catalytic component of telomerase, human telomerase reverse transcriptase [hTERT] has been found to be reactivated in immortalized cell lines and considered as a diagnostic marker for malignancy in different body tissues. Therefore we thought to determine whether hTERT gene detection could serve as an adjunct in the diagnosis of thyroid lesions together with evaluation of its prognostic value. The study included 50 cases of primary thyroid carcinoma including; 28 papillary carcinoma, 14 follicular carcinoma, 5 anaplastic carcinoma and 3 medullary carcinoma in addition to 5 cases of nodular hyperplasia and 5 cases of follicular adenoma. RNA was extracted from paraffin sections of those patients and hTERT gene expression was identified by Reverse Transcription-Polymerase Chain Reaction [RT-PCR]. RT-PCR of hTERT gene revealed expression in 43/50 [86%] malignant thyroid cases; including 25 papillary, 11 follicular, 4 anaplastic and 3 medullary carcinoma cases. On the other hand, hTERT gene expression could not be detected in either hyperplastic nodule or in follicular adenoma cases. The diagnostic validity of hTERT gene detection in benign and malignant thyroid lesions was in the form of 88.3% accuracy, 86% sensitivity, 100% specificity, 100% positive predictive value and 90% negative predictive value. No significant association has been found between hTERT gene expression and any clinicopathologic parameters concerned in this study. In thyroid carcinoma cases, hTERT gene detection was the most independent predictor of poor survival by multivariate survival analysis. Detection of hTERT gene expression should be considered in confirmation of malignant thyroid lesions. Moreover it could be one of the helpful tools in addition to grade, tumor type, and age to stratify patients with thyroid carcinoma into different prognostic categories. Hence, inhibition of hTERT could be of use prospectively in the era of cancer therapy as an attractive weapon in thyroid carcinoma

Epithelial-mesenchymal interaction in rhino-bronchial remodeling

The clinical phase and outcome of allergic diseases is related to the degree of bronchial and nasal remodeling. The present study aimed at assessing some features of both upper and lower airway remodeling in allergic patients as well as the role of epidermal growth factor and its receptor [EGFR] and transforming growth factor fi [TGF-fi] in this process.Twenty patients with mild persistent asthma according to G1NA guidelines and mild persistent allergic rhinitis [ARIA] were included in the present study. Fibreoptic bronchoscopy was done during stable disease. Forceps biopsy was taken from a segmental bronchus and from the nasal turbinates. The biopsies taken were stained by haematoxylin and eosin [H and E] for histopathologic evaluation and immunohistochemical detection of EGFR and TGF-ft was done.Abnormalities in nasal epithelium [ulceration, atypia, and basement membrane thickening] were detected in 50% of asthmatic patients and abnormalities in bronchial epithelium were detected in 40% of them. EGFR was expressed in all abnormal nasal and bronchial epithelium specimens. TGF-f$ was expressed in 90% of abnormal nasal epithelium and all abnormal bronchial epithelium. Both factors were expressed only in hypertrophied nasal and bronchial mucus glands and some inflammatory cells. They were positively correlated with both nasal and bronchial basement membrane thickness.Remodeling occurs even in mild allergic patients. Epithelial-mesenchymal interaction through EGFR and TGF-/3 release plays a major role in this process

Estimation of time passed since death by ultrastructure, histopathology and DNA degradation detection by gel electrophoresis in albino rats

The estimation of postmortem interval [PMI] is of great importance in both criminal and civil cases. However this aim remains critical, difficult if not impossible but an imprecise task in forensic investigation. While the traditional thanatochronological changes upon the dead had been used for estimation of PMI inaccurately, advances in molecular biology, have propelled the analysis of DNA to criminal laboratories. Upon the death of an individual, internal nucleases contained within the cell should cause chromosomal DNA to degrade into increasingly smaller fragments over time that can be used as a predictor of PMI. Liver cells for being rich in nuclear DNA and mitochondria were proved to be the best material for the purpose. The aim of the work was to determine the time passed since death by measuring the rate of DNA degradation in samples of livers of albino rats at different post mortem intervals by using gel electrophoresis method, and to asses the changes of liver cells by histopatological examination at the same periods, with exploring the nature of the post mortem liver cell changes by using the Transmission Electron Microscope [TEM]. Passive engorgement of the sinusoids and extravasations of blood elements appeared early after death in histopathology then cell necrosis, shrunken cells, and apoptotic bodies were increasing by time. TEM examinations revealed the presence of chromatin condensations and fragmentation of the nuclear material. Finally cell lysis and apoptotic bodies appeared while cell necrosis was prominent. Electron microscope could add much to understanding postmortem cellular changes, also assessment of the relative existence of necrosis stages in histopathology might help in identifying PMI. The Gel Electrophorsis detection, measurement and analysis by computer pro analyzer revealed the presence of sequential relationship between DNA degradation level and time passed since death at the DNA visualizing positions [200 bp, 400 bp, 600 bp] up to 24 hours. Statistical evaluation showed a highly significant dependence of DNA degradation on time with P < 0.001. By using linear regression analysis an equation to define the time passed since death could be conducted where: Time after death=[DNA degradation - constant] / B. So it is recommended to apply the method of the gel electrophoresis to detect time passed since death by measuring DNA fragmentation from liver cells. These mathematical relations offer a simple and valuable means of estimating the PMI, and its validity should be tested for human being

role of calcium channel blockers in the treatment of diabetic nephropathy

Diabetic nephropathy [DNP] is a chronic renal disease [CRD] and a major cause of illness and premature death in people with diabetes mellitus [DM]. It is the single most important cause of end-stage renal disease in the Western world and accounts for more than a quarter of all end-stage renal diseases. This article reviews the current development in DNP and the therapeutic challenge with particular reference to the role of calcium channel blockers. Moreover, renal ischaemia hastens the progression of DNP. Diltiazem and amlodipine have a tendency to reverse the changed parameters toward normal values but do not affect the biochemical parameters. Generally speaking, diltiazem is better than amlodipine in reversing biochemical and histopathological changes produced by DNP, and captopril reverses most of the changed parameters with the exception of the histopathological changes. These agents have nephroprotective properties and delay the progression of DNP

mechanism of action of calcium channel blockers in the treatment of diabetic nephropathy

Three types of calcium channels have been identified voltage-sensitive, receptor operated [cardiac muscle and vascular smooth muscle] and stretch operated [in some blood vessels] channels. Using electrophysiological and pharmacological techniques, three different types of voltage-gated calcium channels have been identified, namely, L-type [for long lasting, large channels], T-type [for transient, tiny channels] and N-type [for neuronal, neither L nor T]. Many compounds are known to have a calcium channel inhibitory effect. Calcium antagonists, based on the specificity of inhibition of the slow calcium current, can be classified into three groups: Group A: for 90 to 100 percent inhibition of calcium influx without change in the sodium current [verapamil, diltiazem and the dihydropyridines]; Group B: for 50 to 70 percent inhibition of calcium influx current without change in the sodium current [bepridil, cinnarizine and prenylamine] and Group C: for agents exhibiting some inhibition of calcium influx [phenytoin, indomethacin and propranolol]. There is now increasing evidence that, certain calcium channel blockers especially the dihydropyridines are more strongly associated with vasodilation of afferent arterioles than of efferent arterioles and also with increase intraglomerular pressure and albuminuria. Thus they have a beneficial effect in terms of reducing proteinuria and slowing the progression of diabetic renal failure