DNA repair genes polymorphisms and risk of colorectal cancer in Saudi patients

Background and study aims: Polymorphisms in the DNA repair genes may influence individual capacity to repair DNA damage, which may be associated with increased genetic instability and carcinogenesis. Our aim was to evaluate the relation of genetic polymorphisms in 2 DNA repair genes, XPD Lys751Gln and XRCC1 [A399G], with colorectal cancer [CRC] susceptibility. We further investigated the potential effect of these DNA repair variants on clinicopathological parameters of CRC patients

Patients and methods: Both XPD and XRCC1 polymorphisms were characterised in one hundred CRC patients and one hundred healthy controls who had no history of any malignancy by polymerase chain reaction restriction fragment length polymorphism [PCR-RFLP] method and PCR with confronting two-pair primers [PCR-CTPP], using DNA from peripheral blood in a case control study

Results: Our results revealed that the frequencies of GG genotype of XRCC1 399 polymorphism were significantly higher in the CRC patients than in the normal individuals [p

Conclusion: Our results suggested that, XRCC1 gene is an important candidate gene for susceptibility to colorectal carcinoma

Protective role of curcumin against 2,3,7,8-tetrachlorodibenzo-dioxin-induced histological and biochemical changes in fundic mucosa of the adult rat stomach

2,3,7,8-Tetrachlorodibenzo-dioxin [TCDD] is released into the environment from different activities and industrial sources, with a higher incidence of gastric exposure. This work aimed to study the histological and biochemical changes induced by TCDD in the fundic mucosa and the possible protective role of curcumin against these changes. Thirty adult female albino rats were classified into three groups: the control group [group I]; the TCDD group [group II], in which rats received 100 microg/kg TCDD orally for 3 months; and the curcumin+TCDD group [group III], in which rats received an oral dose of 80 mg/kg curcumin in concurrence with TCDD for 3 months. The serum level of the gastrin hormone was measured. Samples from the fundus of the stomach were stained with H and E, Van Gieson, and PAS/alcian blue and for immunohistochemical detection of aryl hydrocarbon receptors [AHR] and chromogranin A. Morphometric and electron microscopic studies were also carried out. Hyperplasia and metaplastic mucosal changes, together with enteroendocrine cell hyperplasia, were evident. Moreover, glandular degeneration, areas of atrophic gastritis, cellular apoptosis, and gastric ulcers were detected. The previous results could be explained by both TCDD-induced hypergastrinemia and increased AHR expression. In contrast, curcumin appeared to have a propitious protective effect against TCDD-induced gastric affection. Most of the TCDD-induced gastric changes were not observed in group III. It was concluded that the gastric mucosa is sensitive to the toxic effects of TCDD and curcumin can be used to avoid TCDD-induced gastric complications

structure of the optic nerve after the administration of interferon alpha-2a in adult male albino rats and the role of alpha-lipoic acid supplementation

Interferon alpha [IFN-alpha] therapy is used considerably in Egypt because of a high prevalence rate of chronic hepatitis C virus infection. Alpha-Lipoic acid [ALA] has been found to play a neuroprotective role in many insults. The aim of this study is to observe the histological structure of the topic nerve of rats after an injection of IFN-alpha and to determine the role of ALA supplementation. Forty adult male albino rats were divided equally into four groups. Group I served as the control group. Group II included rats that received ALA alone [100mg/kg/day, intraperitoneally]. Group III included rats that received IFN-alpha alone [100000 IU/kg/three times/week, intraperitoneally]. Group IV included rats that received both IFN-alpha and ALA. After 8 weeks, the optic nerves were extirpated and processed for light and electron microscope examination. Optic nerves of the group that received IFN-alpha showed nerved damage manifested as axonal damage and changes in the myelin sheath. Neuroglia showed vacuolation in their cytoplasm and heterochromatic nuclei. Morphometric and statistical analyses showed a significant increase in the surface area of positive glial fibrillary acidic protein astrocytes, indicating reactive astrogliosis. Blood capillaries were distorted with ill-defined walls and protrusion of the endothelial cells into their lumina. These changes were limited by concomitant ALA supplementation with IFN-alpha. IFN-alpha exerted a deleterious effect on the histological structure of the optic nerve in rats and ALA supplementation minimized these effects

Possible protective role of L-carnitine on diclofenac induced hepatotoxicity in adult male albino rats [histological, immunohistochemical and biochemical study]

Diclofenac [DCLF] is in common use worldwide as non steroidal anti-inflamatory drugs [NSAIDs] that have been reported to cause significant adverse effects. L-Carnitine has been proposed as antioxidant because it helps reduce oxidative stress. This work aimed to study the possible histological, immunohistochemical and biochemical changes of liver associated with diclofenac administration and to assess possible beneficial role L- carnitine [LC] on diclofenac [DCLF] induced hepatotoxicity. Fifty adult male albino rats were divided into 4 main groups. Group I: Served as positive and negative controls. Group II: Received LC in a dose of 50 mg/ kg intramuscular [IM] in 1 ml saline. DCLF treated group [III]: Received DCLF 50 mg/ kg IM in 1 ml saline. Combined group [IV]: Rats received LC then DCLF after 2 hours IM. The treatments were given for the rats 6 days/ week for two weeks. At the time of sacrifice, the rats were anaesthetized; blood samples were taken for measuring liver function tests. Specimens from the liver of each rat were taken for light and electron microscopic examination. Histological examination of the liver of the rats of DCLF treated group revealed different degrees of focal lobular affection. Enlarged portal areas, congested portal and central veins, bile duct proliferation, cellular infiltration and fibrosis were detected. Significant decrease in area% of brown positive immunoreactions for glutathione peroxidase I [GPXI] was detected in comparison with control group. Necrosis of most of hepatocytes especially in those close to portal area was detected. Most of hepatocytes mitochondria appeared with ruptured membrane. Pretreatment with LC in combined group showed slight histological changes with sinusoidal congestion, minimal fibrosis around prominent portal area with significant increase in area% of GPX1 in comparison with DCLF treated group. Most of mitochondria appeared with intact membrane. There were significant elevations in liver function tests in DCLF treated group when compared with other groups with partial recovery in combined group. Results obtained in this study demonstrated that high doses of DCLF induced histological and biochemical changes in the liver due to oxidative stress and that the use of LC had partially reduced the DCLF induced toxicity. This may suggest that LC enhanced antioxidant defence and may be used as a cell protector for DCLF induced hepatotoxicity

Influence of Gibberellic Acid [GA3] on Renal Cortex of Adult Male albino Rats [Histological, Immunohistochemical and Biochemical Study]

Plant growth regulators [PGRs] especially gibberellic acids [GA3] are widely used in Egypt to increase plant size, production and to increase plant availability all the year. Little is known about the biochemical or physiological effects of GA3 in mammalian tissues. This study aimed to evaluate the histological, immunohistochemical and biochemical changes in the rat renal cortex with subacute and subchronic exposure to GA3 and to detect the possible mechanism of such toxicities. Fifty adult male albino rats were classified into control group [I], experimental group [IIa and IIb] received GA3 in a dose of 75ppm [part per million]. Seventy five parts per million of GA3 as drinking water for 2weeks in subgroup IIa [subacute exposure] and for 8 weeks in subgroup IIb [subchronic exposure]. Group III [recovery group]: Rats received GA3 for 8weeks and stopped for other 6weeks. Renal cortex was stained with H and E, Masson's trichrome, immunohistochemically for Bcl-2 protein and electron microscopic examination. Oxidative biomarker [MDA] was detected in kidney tissue and antioxidant enzymes were detected in erythrocyte pellets prepared from blood sample. GA3 administration in group [II], led to degeneration, necrosis, apoptosis of the epithelial cells lining some of the tubules of the renal cortex with subacute toxicity and in most of the tubules with subchronic toxicity, fibrosis is significantly apparent in the subchronic subgroup. Interstitial cellular infiltration and hemorhage were seen. Hyaline casts in the lumen of renal tubules were apparent in the subchronic subgroup. Area percentage of antiapoptotic protein Bcl-2 immunoreactivity was decreased in the subchronic subgroup. Picture of cystic glomerular atrophy, acute tubular necrosis, degenerated podocytes and thickened blood renal barrier became prominent in the subchronic subgroup. The histological changes were associated with biochemical markers of oxidative stress. These changes were reduced in the recovery group but not retained to normal and the picture of oxidative stress was still present. The findings implied that gibberellic acid [GA3] induced nephrotoxic effect associated with oxidative stress with some sort of self recovery after stoppage of exposure. So, gibberellic acid should be used cautionary. Also, producers and consumers should be in conscious on the probable toxic effects of these chemicals

Histological changes induced by experimental renal failure in the lung of adult male albino rats and the role of melatonin supplementation

Chronic renal failure may affect virtually every system in the body. The most common uremic consequences in the respiratory tract are disturbed pulmonary function and weak respiration. The present study was designed to evaluate the histological changes induced by experimental renal failure in the lung of adult male albino rats and the possible protective role of melatonin as antioxidant. Forty five adult male rats were equally classified into control group and two experimental groups [15 animals each]. In experimental group I, the rats were submitted to experimental renal failure by five sixths renal ablation. In group II, the nephrectomized rats were treated with melatonin [10 mg/l00 ml/day] orally for 12 weeks. The development of renal failure was monitored by serial estimation of serum creatinine and urea levels. At the time of sacrifice, all rats were anesthetized with ether and their lungs were dissected out and processed for light and electron microscope examination. The nephrectomized rats showed significant elevation in serum creatinine and urea levels. Light microscope examination of their lungs revealed massive cellular infilteration and congestion of blood vessels with marked thickening of their walls. The bronchiolar epithelium was distorted. Some collapsed alveoli appeared with narrow spaces. They were separated by thick interalveolar septa containing cellular infilteration, red blood cells, congested capillaries and fibrous tissue. Intra-alveolar macrophages and red blood cells were seen. Furthermore, electron microscope examination revealed pneumocyte type II with indented nuclei, few microvilli and loss of their secretory granules. Some collapsed alveoli were seen with thick interalveolar septa containing abundant collagen fibers and congested blood capillaries. Disorganized blood air barriers were observed. The nephrectomized rats treated with melatonin showed non significant elevation in serum creatinine and urea levels. Light microscope examination of their lungs revealed intact bronchioles and alveoli with some congested blood vessels and few cellular infilteration. Electron microscope examination showed intact pneunocyte type II and blood air barrier. The present study revealed that experimental renal failure induced adverse effects on the histological structure of the lung which was partially improved by melatonin supplementation. Clinical and experimental studies are recommended to explore the efficacy of melatonin in renal failure. If proven effective, melatonin would be an adjunctive therapy, since it is natural, orally administrated and relatively safe

possible beneficial effect of angiotensin II receptor antagonist [Losartan] in experimental-hepatic fibrosis in albino rats. histological immunohistochemical and biochemical study

Hepatic fibrosis is a histological change caused by liver inliammation and characterized by accuix of extracellular matrix protein [ECM]. Losartan is one class of drugs that inhibit the action of angiotensin II [A' H at its receptors. It has been used as antihypertensive in human. Was to clarify the beneficial effect of losartan in experimental liver fibrosis by bile duct li-z. Forty adult male albino rats were divided into four equal groups; GI [control], Gil operated], Gill [bile duct ligated, BDL] and G VI received losartan at a dose of 5 mg/kg daily after BDL. After fc weeks, blood samples were collected for estimation of serum bilirubin [SB], alanine aminotransferase [ALT], aspare aminotransferase [AST], alkaline phosphatase [ALP] and serum hyaluronic acid [SHA]. Rats were sacrificed and th livers were processed for estimation of hydroxyproline and for histological study. Paraffin sections were stained b H and F, Masson's trichrome and other sections were stained immunohistochemically for desmin. Revealed elevated liver enzymes, serum and tissue fibrosis markers [hyaluronic acid and hydrox-cr together with dramatic histological changes in liver sections of G III [BDL]. Administration of Losartan after BDL C-V showed improvement of biochemical analysis of liver enzymes, fibrosis markers and amelioration of the his o1oria changes of hepatic tissues. Moderate expression of desmin from hepatic stellate cells [HSCs] was also evident Fr this study. That losartan has a benifical effect in liver fibrosis induced by BDL. However, further study for its usefulness in human hepatic fibrosis is recommended

study of Helicobacter pylon in dyspeptic patients with and without decompanseated liver disease

Helicobacter pylori infection was investigated by two different methods, microscopically and biochemically in 200 dyespeptic patients [149 male and 51 female] aged from 40-70 years. All patients divided into two groups, the first one as control group [100] and without liver cell failure, the second studied group [100] as diseased group with liver cell failure. Helicobacter pylori infection was diagnosed in 54% in the first group and 78% in the second group. The Helicobacter pylori prevalence in the second group of liver cell failure was significantly higher than in the first control group and was not correlate to the sex difference, etiology of the liver cell failure, child classification or any endoscopic finding of gastroduodenal mucosal lesion. In both groups Helicobacter pylori infection was significantly higher in patients over 40

Clinical and ultrasonographic prediction of Oesophageal varices in liver cirrhosis

Since bleeding from oesophageal varices is a major complication of chronic liver diseases among Egyptians, early diagnosis of portal hypertension and varices may prevent and control bleeding. 139 patients with chronic liver disease of different grades were classified and investigated. 89 with no varices, 27 with small and 23 with large varices. Clinical examination, liver functions, blood picture, hepatitis markers, rectal snips for bilharzial ova, upper gastrointestinal endoscopy and abdominal ultrasonography with Doppler study of portal vein, splenic vein and hepatic artery were done for every patient. The results showed significant relation between presence of oesophageal varices and hepatic coma, spider navi, ascites and increased score of child classification. There was significant positive relation between splenic size and negative relation of liver size and presence or grading of varices. A significant positive relation was found between presence of varices and post hepatitic cirrhosis. A significant increase in total bilirubin, AST, ALT, ALKphos., and decrease in serum albumin and prothlrombin concentration in patients with varices as well as a significant decrease in R.B.Cs, W.B.Cs, Platelets and HP% in the group with varices. Doppler study revealed increase in P. V.D, P. V.C.A, and decrease in P. V.C.I and P. V.M. V in patients with varices. Doppler study on hepatic artery showed good correlation of H .A. P.I, L V.I but not H.A.M. V and the presence of varices. No parameter was found to differentiate small from large varices except splenic size and ascites. This leads to the conclusion that clinical, ultrasonic and Doppler examinations of hepatic patients may suggest the presence of varices without, need for endoscopic examination of every patient

Distribution of P53 and mdm2 genes in patients with hepatocellular carcinoma

50 patients with hepatocellular carcinoma, 36 males and 14 females 14-73 years old were studied in this work. Abnormal values of s.. bilirubin. AST, ALT and alkaline phosphatase were found in 52, 64 and 76% of cases respectively. 70%of cases had AFP levels between 50 and 150ng/dl while 6/had levels below 10ng/dl. 46.had stage 1:36 stage II and 18/had stage III disease. P53 was overexpressed in 46% of cases not related to age or sex. A statistically significant relationship was found between mdm2 overexpression and the stage of the tumor. 42% of cases were P53 positive and mdm2 negative and 24% of cases were P53 negative and mdm2 positive that may indicate that mdm2 overexpression and P53 mutation represent alternative mechanisms for inactivating the same regulatory pathway for suppressing cell growth. Concomitant overexpression of either P53 or mdm2 or both was found to have statistically significant relation with tumour stage indicating that P53 mutation and mdm2 overexpression are alternative mechanisms for inactivating the same pathway for suppressing cell growth. It can be concluded that P53 in activation may be involved in the molecular pathogenesis of HCC and its mutation is late in HCC and its frequency is related to tumour progression mdm2 overexpression has the same significance. Tumors with mdm2 overexpression were devoid of P53 mutations and vice verca; indicating that they represent alternative mechanisms for inactivating the same regulatory pathway for suppressing cell growth

Microalbuminuria in diabetics with coronary heart disease

Microalbuminuria was determined in 40 patients with type II diabetes mellitus [10 without coronary heart disease [group I] and 30 with CHD [group II]] before and after exercise, using automated immunoprecipitin analysis. Microalbuminuria in group I showed significant increase before [P <0.05] and after exercise [P <0.001] when compared with control. Diabetic group with CHD showed significant increase in microalbuminuria before and after exercise [P <0.05]. Both patients in group I and group II showed in significant changes in microalbuminuria before and after exercise [P >0.05]. However, these results were obtained from a small number of selected diabetic patients with or without coronary heart disease

Medical problems among Egyptian potential kidney donors

At Mansoura Urology and Nephrology Center, 136 potential living kidney donors were medically evaluated before donation to study the frequency of medical problems among them. Seventy seven [56.62%] cases were excluded because of medical diseases. The most frequent causes of exclusion were renal diseases [36.36%], HLA mismatching [18.18%], hepatic diseases [14.29%], and cardiovascular diseases [11.69%]. Infection due to viral hepatitis, tuberculosis, and cytomegalovirus constituted 2.94%, 2.21% and 1.29% from all studied cases respectively. Exclusion due to unaccepted age, diabetes mellitus, and unwilling was found in 3.90% in each cause. Schistosomiasis represented 2.6% of excluded cases. Among the renal diseases, asymptomatic haematuria [42.87%], polycystic kidney diseases [14.26%] and renal stones [10.73%] represented the major renal problems. In spite of the small number of studied potential kidney donors, the high frequency of medical problems among them may be a mirror of the health status of Egyptian donors which needs an open discussion for the legalization of cadaver donation

Prevalence of hepatitis C virus in personnel working in Kafr El-Zait fever hospital

This study was conducted on 37 medical and allied medical personnel 19 apparently healthy individuals as a controls. All the 56 persons were examined for anti-HCV by a qualitative enzyme immunoassay. The results showed that 21.6% of the medical personnel and 15.8% of the control group were positive for anti-HCV, but the difference was not statistically significant. Prevalence of anti-HCV was lowest [5.3%] in nurses with significant difference when compared to other medical personnel. Similarly their mean age was significantly lower than the remaining personnel. The mean duration of employment was significantly longer in medical personnel positive for anti-HCV than negative ones [P < 0.05]. The serum alanine aminotransferase [ALT] showed significantly higher values in those positive for anti-HCV as compared to negative subjects. This high prevalence of anti-HCV may be an alarm for the size of the problem of HCV in Egypt

Comparative effectiveness of azathioprine and cyclosporine in the treatment of steroid resistant and steroid dependent idiopathic nephrotic syndrome

This study was conducted on 40 patients with idiopathic nephrotic syndrome [24 males and 16 females] with a mean age of 9.7 years +/- 3.19 years [from 4-16 years]. Based on the previous response to corticosteroids there were 21 [52.5 percent] steroid resistant [SR] and 19[47.5 percent] steroid dependent [SD] cases. Out of the 40 patients there were 24 [60 percent] with minimal change nephrotic syndrome [MCNS], 9 [22.5 percent] with focal segmental glomerulosclerosis [FSGS] and 7 [17.5 percent] with mesangoproliferative glomerulonephritis [MPGN]. All patients were randomized to receive prednisone [1 mg/kg/day for 8 weeks to be gradually decreased] with either azathioparine [Aza group] in a dose of 2 mg/kg/day or cyclosporine [Cs group] at an initial dose of 5 mg /kg/day. Both Cs and Aza were given for 12 weeks. All patients had follow up for one year from the start of treatment. There were no significant differences [P>0.05] in the results of treatment between Aza and Cs group in either SR or SD cases. However, Cs resulted in 100 percent remission [complete remission in 66.7 percent and partial remission in 33.3 percent] after 3 months of treatment in cases with MCNS with significant difference [P<0.05] when compared to Aza group. No significant difference was found between Aza and Cs group in patients with either FSGS or MPGN

effects of a hemodialysis session on left ventricular function in patients with chronic renal failure under maintainance hemodialysis

The effects of a haemodialysis session [D. S] on the left ventricular function [LVF] were studied in 31 patients [77% males and 23% females] with end stage renal failure. Their mean age was 30. 4 +/- 7 83 years [17- 42 years] and they have been on maintainance haemodialysis for 2 months to 5 years [mean duration 19. 9 +/- 13. 61 months]. Echocardiograhic study revealed that the D. S. resulted in significant decrease [P< 0.05] in the mean end systolic diameter and volume; mean end diastolic diameter, end diastolic volume and volume index. Similarly, there was a significant decrease in the mean stroke volume and mean left ventricular ejection time. In the mean time, there was a significant increase in the mean ejection fraction and the mean circumferential fiber shortening velocity. It was evident from our work that, the D. S resulted in partial correction of serum electrolytes imbalance and metabolic abnormalities. There was a consequent improvement in the echocardiographicaly determined L VF [as reflected by decrease in left ventricular dimensions and volumes] with better contractility. Accordingly, it can be assumed that, the disturbed left ventricular cardiac functions found prior to dialysis are mainly due to functional rather than structural changes

Doppler echocardiographic determination of pulmonary pressure: a simultaneous doppler catheterization study in patients with pulmonary hypertension

Pulmonary artery pressure [PAP] was estimated by both catheter and Doppler techniques in 23 patients with pulmonary hypertension. All patients had tricuspid and pulmonary regurgitation. Utilizing different methods for estimating [PAP], the pulmonary regurgitant flow velocity method was used to estimate mean [PAP] and diastolic [PAP]. A good correlation was found between this method and cardiac catheter, p< 0.01, the sensitivity was 90% and specificity was 95%. Tricuspid regurgitant flow velocity method for estimation of systolic [PAP] showed high accuracy with systolic [PAP] determined by catheterization, p < 0.01 and sensitivity was 92% and specificity was 95%. Using time peak velocity of pulmonary flow [AT] to measure mean [PAP], there was a tendency for over estimation in patients with [AT] 80 msec., On the other hand patients with [AT] < 80 msec. showed 80% sensitivity and a 98% specificity for detection of elevated [PAP]. So peak tricuspid velocities provided unexpectedly difficult record in some patients but when successful, it provides excellent prediction of pressures. Recording of mean [PAP] from [AT] of pulmonary artery wave form was very easy but accuracy was limited was limited to whom [PAP] was high. In contrast, pulmonary regurgitation velocities were easily obtained and provided high accuracy results

Effect of calcium antagonists on left ventricular and ventilatiory functions in patients with ischaemic heart and obstructive airway disease

The aim of this study is to assess the effect of calcium antagonists on left venticular and ventilatory functions in patients with ischaemic heart disease associated with obstructive lung disease. The material of this work comrised [10] healthy subject as a control group and [20] patients with symtomatizing ischaemic heart disease associated with obstructive airways diseases- as a test group, the test group was divided into two subgroups, one assigned for use of Verapamil [10] patients and the other for Nifedipine [10] patients. After taking detailed clinical history and parforming careful physical examination, all patients were subjected to, urine and stool analysis, fasting blood sugar X- ray film ECG, measurements of systolic time intervals [STIs] including [Q-S21], PEP1, LVET and PEP/ LVET ratio] and ventilatory function tests, including [FVC, FEV1 and FEV1/FVC%]. STIs and ventilatory parameters were done before and in the 10[th] day of using either Verapamil or Nifedipine. Comparative analysis of STIs in both subgroups assigned for use of either Verapamil or Nifedipine showed left ventricular dysfunction as shown from the significant prolongation of PEPI, shortening of LVET and rise in PEP/LVET ratio, also insignificant prolongation of Q-S21 was observed, indicating mild left ventricular dysfunction. On the other hand, comparing the same parameters of STIs after versus before use of either Verapamil or Nifedipine. Showed no significant prolongation of PEPI, shortening of LIVT1 or rise in PEP/LVET ratio. Comparative analysis of ventilatory parameters after versus before the use either Verapamil or Nifedipine Showed non-significant changs. It may be concluded, that left ventricular dysfunction is found in patients with ischaemic heart disease associated with obstructive airways disease, and the use of either Verapamil or Nifedipins drugs is safe in such patients, as they produces mild negative inotropy and left ventricular dysfunction which were short of significance and negligable in comparison to its benificial effect, on the other hand have no adverse or improving effect on ventilatory function in patients with chronic obstructive airway diseases