Histological and Physiological Studies of the Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Bleomycin Induced Lung Fibrosis in Adult Albino Rats

BACKGROUND@#Lung fibrosis is considered as an end stage for many lung diseases including lung inflammatory disease, autoimmune diseases and malignancy. There are limited therapeutic options with bad prognostic outcome. The aim of this study was to explore the effect of mesenchymal stem cells (MSCs) derived from bone marrow on Bleomycin (BLM) induced lung fibrosis in albino rats. @*METHODS@#30 adult female albino rats were distributed randomly into 4 groups; negative control group, Bleomycin induced lung fibrosis group, lung fibrosis treated with bone marrow-MSCs (BM-MSCs) and lung fibrosis treated with cell free media. Lung fibrosis was induced with a single dose of intratracheal instillation of BLM. BM-MSCs or cell free media were injected intravenously 28 days after induction and rats were sacrificed after another 28 days for assessment. Minute respiratory volume (MRV), forced vital capacity (FVC) and forced expiratory volume 1 (FEV1) were recorded using spirometer (Power lab data acquisition system). Histological assessment was performed by light microscopic examination of H&E, and Masson’s trichrome stained sections and was further supported by morphometric studies. In addition, electron microscopic examination to assess ultra-structural changes was done. Confocal Laser microscopy and PCR were used as tools to ensure MSCs homing in the lung. @*RESULTS@#Induction of lung fibrosis was confirmed by histological examination, which revealed disorganized lung architecture, thickened inter-alveolar septa due excessive collagen deposition together with inflammatory cellular infiltration. Moreover, pneumocytes depicted variable degenerative changes. Reduction in MRV, FVC and FEV1 were recorded. BM-MSCs treatment showed marked structural improvement with minimal cellular infiltration and collagen deposition and hence restored lung architecture, together with lung functions. @*CONCLUSION@#MSCs are promising potential therapy for lung fibrosis that could restore the normal structure and function of BLM induced lung fibrosis.

Histological and Physiological Studies of the Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Bleomycin Induced Lung Fibrosis in Adult Albino Rats

BACKGROUND@#Lung fibrosis is considered as an end stage for many lung diseases including lung inflammatory disease, autoimmune diseases and malignancy. There are limited therapeutic options with bad prognostic outcome. The aim of this study was to explore the effect of mesenchymal stem cells (MSCs) derived from bone marrow on Bleomycin (BLM) induced lung fibrosis in albino rats. @*METHODS@#30 adult female albino rats were distributed randomly into 4 groups; negative control group, Bleomycin induced lung fibrosis group, lung fibrosis treated with bone marrow-MSCs (BM-MSCs) and lung fibrosis treated with cell free media. Lung fibrosis was induced with a single dose of intratracheal instillation of BLM. BM-MSCs or cell free media were injected intravenously 28 days after induction and rats were sacrificed after another 28 days for assessment. Minute respiratory volume (MRV), forced vital capacity (FVC) and forced expiratory volume 1 (FEV1) were recorded using spirometer (Power lab data acquisition system). Histological assessment was performed by light microscopic examination of H&E, and Masson’s trichrome stained sections and was further supported by morphometric studies. In addition, electron microscopic examination to assess ultra-structural changes was done. Confocal Laser microscopy and PCR were used as tools to ensure MSCs homing in the lung. @*RESULTS@#Induction of lung fibrosis was confirmed by histological examination, which revealed disorganized lung architecture, thickened inter-alveolar septa due excessive collagen deposition together with inflammatory cellular infiltration. Moreover, pneumocytes depicted variable degenerative changes. Reduction in MRV, FVC and FEV1 were recorded. BM-MSCs treatment showed marked structural improvement with minimal cellular infiltration and collagen deposition and hence restored lung architecture, together with lung functions. @*CONCLUSION@#MSCs are promising potential therapy for lung fibrosis that could restore the normal structure and function of BLM induced lung fibrosis.

Electron microscopic study of the left caput epididymal epithelium of adult albino rats in an experimental left varicocele model

Varicocele is a vascular lesion characterized by dilatation and tortuosity of the pampiniform plexus of the spermatic cord. It is one of the most common causes of male infertility. Most studies have focused on testicular function. Meanwhile, there are limited data in the literature on its impact on the epididymal structure. The aim of this study was to assess the effect of an experimental left varicocele on the histological structure of the left caput epididymis of adult albino rats and the cauda epididymal sperm count. Forty adult male albino rats [220-250 g] were randomly allocated to four equal groups. In group I [control group], rats did not undergo any surgical intervention. In group II [sham-operated group], animals underwent sham operation. The rats of groups III and IV underwent partial ligation of the left renal vein to create a varicocele and were sacrificed after 4 weeks and 8 weeks, respectively. Left caput epididymal strips of five rats of each group were harvested and prepared for light and electron microscopic examinations. Sperm samples were obtained from the left cauda epididymides of the remaining animals of each group for sperm count, and the results were statistically analyzed. There was a positive correlation between the sperm count and the duration of varicocele. Group III rats revealed a significantly lower sperm count as compared with the control and sham-operated groups. A significantly greater reduction in the sperm count was found in group IV rats as compared with group III rats. Histologically, varicocele-induced left caput epididymal alterations mainly involved the principal cells. They included cytoplasmic vacuolation and widening of the intercellular spaces in semithin sections of group III rats. Ultrastructurally, increased vesicular and vacuolar contents of the apical cytoplasm along with dilatation of Golgi saccules and rough endoplasmic reticulum were observed. The tubular lumina depicted several retained defective spermatids and spermatozoa with retained cytoplasmic droplets. With an increase in varicocele duration [in group IV], apparent thinning out of the lining epithelium with few stereocilia was observed in semithin sections. Ultrastructurally, the principal cells revealed a relatively dense cytoplasm and rather heterochromatic nuclei. The lumina were bordered with short, sparse microvilli and showed several defective spermatozoa. Experimental left varicocele induces evident histological alterations of the ipsilateral caput epididymis of adult rats and also a reduction in the caudal sperm count, both of which are duration dependent

Fibronectin and interleukin-18 renal ischemia with and without reperfusion rats

Ischemia reperfusion is a common leading cause to acute renal failure. Cellular mechanisms include cell adhesion, cell infiltration and generation of oxygen free radicals, and inflammatory cytokine production have been identified, however, the exact causes remain unclear. The aim of the present study was to investigate the role offibronectin [FN], interleukin-18 [IL-18] and serum ferritin in a vivo model of unilateral ischemic and/or reperfused kidney in the rat. In addition, the effects of different durations of ischemia, with or without reperfission on the previous parameters were assessed. This study was carried out on 40 male albino rats divided into 4 groups [10 rats/each]. They were group I: rats were subjected to renal ischemia for 40 minutes without reperfusion; group II: rats were subjected to permanent renal ischemia for 24 hour; group III: rats were subjected to renal ischemia for 40 minutes followed by 24 hour of reperfusion and group IV: sham operated rats. Renal ischemia was induced by clamping the renal artery and vein for 40 or 24 hour mm whereas the contralateral kidney is left intact. At the determined time of sacrifice the blood was collected by cardiac puncture and serum was separated. Both kidneys [left postischemic and right contralateral] were excised and frozen at-80 C for biochemistry. The kidneys were homogenized and used for estimation of fibronectin and IL-18 by EL1SA and serum samples were used to estimate the ferritin by ELISA. The mean value of FN and IL-18 was peaked at 24 h after permanent ischemia in group II, it was significantly high compared with the other studied groups. Forty minutes of ischemia without reperfusion was associated with increased level of FN and IL-18 compared with 40 minutes ischemia with subsequent reperfusion. However, the difference was not statistically significant. Forty minutes ischemia without repeifusion in group I was associated with the highest signicant increase in serum ferritin level. In conclusion, ischemia with or without reperfusion was associated with upregulation of the detected extracellular matrix proteins; spec [flcally FN as well as the detected cytokine; IL-18 from renal tissues. However, the highest increase in these two parameters was observed in permanent ischemia [for 24h] rather than transient ischemia [40 minutes]. The elevated level of FN in permanent ischemia explains its possible role in the regeneration of the damaged kidney and/or fibrosis. Reperfusion has no prominent effect on renal FN and IL-18 levels. Thus, time of ischemia may be the most important determinant for higher FN and 11-18. Moreover, this study had showed that serum ferritin increased significantly in transient ischemia without reperfusion which indicates its role as an acute phase reactant in a response to ischemia

Developmental stuttering and in voluntary movements in schoolaged children in Cairo

Stuttering is a disturbance in the normal fluency and time patterning of speech that is inappropriate for a person's age. Developmental stuttering emerges during the period of rapid language development with two sharp peaks of onset between the ages of 2 to 3 1/2 years and 5 to 7 years. It involves a disruption in the smooth connection of sounds or syllables characterized by multiple interruptions within a word, such as repetitions of sounds, syllables and parts of words, elongation of words and blockades. This study aimed to assess developmental stuttering at its second peak in childhood and evaluate associated involuntary movements. A sample of 932 children [480 boys and 452 girls] aged 5-7 years attending 21 different schools and Kindergartens at different locations in Cairo City were included in the study. Speech, language and hearing development within the normal range, except for stuttering, were insured. Stuttering was considered to be present if 10 or more dysfluencies occurred in every 100 words. Stuttering was detected in 38 children with a prevalence rate of 4.07%. Stuttering severity was found to be 36%, 47.5%, and 15.7% for mild, moderate and severe stuttering respectively. The male to female ratio was 3.2:1. Tics were identified in 26.3% of stuttering children, versus 4.58% non stuttering children with a statistically significant difference in prevalence. Tics in the form of repetitive eye blinks followed by prolonged eye closure were found exclusively in the stuttering group. Left handedness was present in 5.26% of the stuttering children versus 4.13% non stuttering children. In view of the high prevalence of developmental stuttering and significant number of involuntary movements revealed - by the study, a mass screening program for early diagnosis and referral in this high risk group is recommended

Study of tumor necrosis factor-alpha, leptin, plasminogen activator inhibitor-1 and oxidative stress in obese type 2 diabetic patients: Relation to insulin resistance

Great evidence indicates that some factors secreted by adipocytes are directly involved in the pathogenesis of obesity diabetes syndrome. This work was designed to study the role of tumor necrosis factor-alpha [TNF-alpha], leptin, plasminogen activator inhibitor-1 [PAI-1] and oxidative stress in relation to insulin resistance in obese type 2 diabetic patients. The study included 60 premenopausal women, classified into 4 groups; I] included 15 obese type 2 diabetics II] included 15 lean type 2 diabetics III] included 15 obese non diabetics and IV] included 15 lean non diabetics. All subjects were subjected to complete history taking, thorough clinical examination, anthropometric measurements and laboratory investigations including fasting and 2-hour post load glucose levels, fasting and 2-hour post load insulin levels, lipid profile, plasma TNF-alpha levels, leptin levels, PAI-1 levels and measurement of malondialdehyde [MDA] levels. The present study showed a significant positive correlation between leptin and body mass index [BMI], waist circumference, fasting insulin level and homeostasis model assessment insulin resistance index [HOMA IR], cholesterol and TNF-alpha. The statistical significance of association between leptin in one hand and waist circumference, HOMA, and cholesterol in the other hand was abolished when data were adjusted for BMI. The statistical significance between leptin and fasting insulin and TNF-alpha persisted after adjustment of data for BMI, indicating an independent association between leptin and both fasting insulin and TNF-alpha. There was an independent association between TNF-alpha and fasting glucose, 2-hour post load glucose, leptin and PAI-1. There was independent association between PAI-1 and fasting insulin, 2-hour post load insulin, triglycerides, high density lipoprotein-cholesterol [HDL-C] and TNF-alpha. MDA level was significantly higher in diabetic groups in comparison to the non-diabetic groups. However, there was no correlation between MDA and other parameters. We conclude that leptin, TNF-alpha, PAI-1 and increased oxidative stress may play a role in insulin resistance in obese type 2 diabetic patients

Pharmacological versus exercise stress imaginig for detection of left anterior descending coronary Artery stenosis in patients with left bundle branch block

This study was conducted to assess the diagnostic value of myocardial perfusion imaging during exercise and pharmacologic stress in patients with left bundle branch block. The study was performed on 100 consecutive patients with left bundle branch block referred for perfusion scintigraphy over a 2-year period. Perfusion tomography was performed in conjunction with exercise in 50 patients, adenosine in 25 and dobutamine in 25 coronary angiography was performed within one month of the nuclear study. The study concluded that in patients with left bundle branch block, the pharmacologic stress is more specific than exercise tomography in the diagnosis of left anterior descending coronary artery stenosis. Dobutamine and adenosine tomography appear to be equally specific in these patients

Angioplasty versus surgery trial: a randomized comparison of coronary agioplasty with bypass surgery in patients with dysfunctioning myocardium

This Trial was designed to determine whether percutaneous transluminal coronary angiopiasty [PTCA] is as effective as coronary artery bypass graft surgery [CABG] in restoring arterial perfusion capacity in eligible patients with multivessel disease and dysfunctioning myocardium Of 392 patients, 198 patients were randomized to PTCA and 194 to CABG. Index lesions [2.7 +/- 1.0 per patient] were those with > 50 percent stenosis judged treatable by both angioplasty and surgery. Coronary segments jeopardized by these index lesions were designated as index segments [4.4 +/- 1.4 per patient]. Percent stenosis was measured by quantitative angiography at the point of greatest obstruction in the main perfusion path of each index segment. The primary arteriographic end point was the percent of a patient's index segments with < 50 percent stenosis in the main perfusion pathways at 1 and 3 years. At baseline, the percent of index segments for which revascularization was attempted was 85 percent for PTCA and 98 percent for CABG [P < 0.0001]. At 1 year, PTCA patients had a smaller percentage of successfully revascularized index segments than CABG patients [59 percent versus 88 percent, P< 0.001]. At 3 years, the findings were similar but less striking [70 percent versus 87 percent, P< 0.001]. When only [high-priority] index segments [2.1 +/- 1.6 per patient] were considered, baseline attempts were comparable [96 percent versus 99 percent, P=NS]; despite this, CABG remained more successful at 1 [64 percent versus 93 percent, P< 0.001] and 3 [76 percent versus 89 percent, P < 0.01] years. However, the mean percent of index segments free of severe stenosis [> 70 percent] did not differ between PTCA and CABG patients at 3 years [93 percent versus 95 percent, P =NS]. Furthermore, the frequency of patients with all index segments free of severe stenosis did not differ between the two groups at 1 [76 percent versus 83 percent, P =NS] or 3 [82 percent for both PTCA and CABG] years. In patients with multivessel disease, index segment revascularization was more complete with CABG than PTCA at both 1 and 3 years. However, when the physiological priority of the target lesion and the measured severity of the residual stenosis are taken into account, the advantage of CABG becomes less significant or no significant. This may, in part, explain why these two strategies did not differ in terms of the primary clinical end points over 3 years

study of glycoproteins in rheumatic fever

The serum glycoproteins [protein bound hexose, sialic acid and fucose] were measured in 100 children aged between 5-15 years. Children were carefully selected and classified into four groups, each composed of 25 children. The first group was normal, the second active rheumatic fever, the third group non active rheumatic and the last group the normal siblings of rheumatic patients. The results indicated an increase in all glycoproteins in the active stage of rheumatic fever. The other groups showed insignificant change in glycoproteins levels compared to normal controls. So, serum glycoproteins might be recommended as useful laboratory index of acute rheumatic fever. They might be considered as valuable indices of activity and they might be regarded amongst acute phase reactants

Salivary hyaluronidase during pregnancy

The activity of salivary hyaluronidase. of both tissue and bacterial origin, has been found to increase during the first and third trimesters of pregnancy. The increase in salivary hyaluronidase activity was found to have a relationship to the increase in gingival changes. This may show that the increase in hyaluronidase activity will lead to increase susceptibility to gingivitis

Characterization of liver pyridoxal kinase

Liver pyridoxal kinase consists of one subunit with molecular weight of 60.000 dalton. The enzyme has an isoelectric point of 5.1. The enzyme was stable for 6 h at 37°C; however, at 50°C the activity decreased sharply after 15 min. The activity of the enzyme was unaffected by preincubation with anti-sulfhydryl group reagents, such as N-ethylmelamide, iodoacetate, iodoacetamide, and P-chloromercury benzoate. The amino acid composition of liver pyridoxal kinase was determined. Chemical modification with glyoxal and phenylglyoxal suggested the presence of arginine at the active site. This arginine residue is essential for binding of ATP to the enzyme active site