Hepatoprotective effects of Cynara extract and silymarin on carbon tetrachloride-induced hepatic damage in rats

The aim of this study was to investigate the effect of Cynara scolymus extract alone or in combination with silymarin on the carbon tetrachloride (CCl₄)-induced hepatic injury in rats. Cynara extract (30, 60, or 120 mg/kg), silymarin (25 mg/kg), or Cynara extract (30, 60, or 120 mg/kg) combined with silymarin was given once daily orally simultaneously with CCl₄ and for 2 weeks thereafter. Liver damage was assessed by determining serum enzyme activities and hepatic histopathology. Cynara extract given at the above doses conferred significant protection against the hepatotoxic actions of CCl₄ in rats, reducing serum alanine aminotransferase (ALT) levels by 21 %, 24.3 %, and 35.8 %, respectively, compared to CCl₄ control group. Serum aspartate aminotransferase (AST) levels decreased by 15.5 %, 39.6 %, and 44.3 %, respectively. Alkaline phosphatase (ALP) decreased by 21 % and 25 % by Cynara extract at 60 and 120 mg/kg, respectively. In rats treated with silymarin combined with Cynara extract (30, 60, or 120 mg/kg), ALT decreased by 32.6 %, 34.5 %, and 51.6 %, and AST decreased by 20 %, 50.6 %, and 58.3 %, respectively. Meanwhile, ALP decreased by 22.4 % and 29.7 % after treatment with silymarin combined with Cynara extract (60 or 120 mg/kg). On the other hand, the administration of silymarin alone reduced ALT, AST, and ALP levels by 55.3 %, 67.1 %, and 52.5 %, respectively. The administration of CCl₄ resulted in marked increase in nitric oxide level in serum (the concentrations of nitrite/nitrate) as well as marked decrease in blood levels of reduced glutathione (GSH). Treatment with Cynara extract resulted in a dose-dependent decrease in serum nitric oxide level and increased GSH in blood compared with CCl₄ control group. Silymarin showed an additive effect resulting in further decrease in serum nitric oxide. Silymarin only treatment caused a marked reduction in serum nitric oxide level and increased GSH in blood. Histopathological studies also indicated that CCl₄-induced liver injury was less severe in Cynara extract-treated groups. Metabolic perturbations caused by CCl₄ in hepatocytes such as reduced protein and mucopolysaccharide content were markedly improved by the Cynara extract given at the dose of 120 mg/kg. Intracellular protein and mucopolysaccharide contents were normalized upon treatment with silymarin. The effect of Cynara–silymarin combination was, however, less than that of Cynara extract alone. These results suggest that treatment with Cynara extract protects against CCl₄-induced hepatic injury in rats and might prove of value in treating chronic liver disease in man, although the combination of Cynara–silymarin is not superior to either Cynara extract or silymarin alone.     

Subclinical Vascular Endothelial Dysfunctions and Myocardial Changes With Type 1 Diabetes Mellitus in Children and Adolescents

Vascular endothelial dysfunction, accelerated thickening of arterial intima, and changes in ventricular functions contribute to increased cardiovascular morbidity in type 1 diabetes mellitus (T1DM). This study aimed to investigate the functional-structural changes in the arteries and myocardium together with affection of highly sensitive C-reactive protein (hsCRP), circulating endothelial cells (CECs), and vitamin C levels in children with T1DM. Also, to test the association with early atherosclerotic changes. The study included 30 children with a diagnosis of T1DM and 30 healthy subjects matched by sex, age, and body mass index. Serum lipids, HbA1c, hsCRP, vitamin C, and CECs were detected. Corrected QT interval (QTc), cardiac dimensions, and left ventricular (LV) functions were assessed using conventional echocardiography. Noninvasive ultrasound was used to measure brachial artery flow-mediated dilation (FMD) responses and carotid intima-media thickness (IMT). The QTc interval was significantly higher in the diabetic patients than in the control subjects (P < 0.001). The findings showed LV diastolic dysfunction as reflected by significantly lower early peak flow velocity, decreased E/A ratio, increased early filling deceleration time (DcT), and prolonged isovolumic relaxation time (IVRT) (P < 0.001 for each). The children with diabetes had a significantly lower FMD response, increased IMT, lower vitamin C level, higher hsCRP, and higher CEC compared with the control subjects (P < 0.001 for each). A positive correlation between CEC and HbA1c was found (P = 0.004). An alteration in myocardial function and endothelial dysfunction may begin early with the association of early atherosclerotic changes. These changes are accelerated when glycemic control is poor. The authors recommend early and close observation of children with diabetes for any alterations in cardiac and vascular endothelial function. Vitamin C supplementation may reduce the risk of complications.     

Evaluation of the effect of neoadjuvant chemotherapy on tumor and axillary lymph nodes in locally advanced breast cancer： a study of 50 patients

Objective： The purpose of the study was to correlate between effect of pre-neoadjuvant chemotherapy （NACT） and post-NACT clinical, sonographic and pathologic features of the tumor and axillary lymph nodes （ALNs） and to raise the possibility of applying the concept of sentinel lymph node biopsy （SLNB） in patients with initially positive ALNs before NACT. Methods： A prospective study of 50 female patients with locally advanced breast cancer （LABC） with clinically palpable.and cytologically （under ultrasonographic guidance） positive ALNs. All patients received NACT and then referred for ultrasono- graphic assessment of the axilla regarding any detectable sonographic criteria of metastatic deposits in ALNs as well as the tumor size in relation to its prechemotherapy size, All patients were then subjected either to modified radical mastectomy or breast conserving surgery. The clinical, sonographic and pathological response of the tumor and the ALNs were documented, classified and correlated with each other. Results： Patients＇ mean age was 47.7±9.1 years. The mean clinical tumor size was 6.7 ± 1.4 cm; stage IliA that was presented in 32 patients （64%） and IIIB was presented in 18 patients （36%）. Chemotherapy was given for a median of 4 cycles, there was reduction of the mean clinical tumor size from 6.7 ± 1.4 cm to 4.3 ± 2.7 cm （P 〈 0.001）. Clinical response was complete in 5 （10%） tumors, complete pathological tumor response （post-neoadjuvant） was detected in 6 （16%） of patients. Complete clinical nodal response （post-neoadjuvant） in 23 （46%） axillae, on sonographic assessment of the axilla, response was complete in 17 （34%） axillae. Complete pathological nodal response occurred in 16 （32%） axillae. Out of 17 axillae that showed complete sonographic response 11 axillae showed complete pathological nodal response （P 〈 0.001）. Conclusion： Formal axillary lymph node dissection can be avoided and replaced by SLNB post NACT in patients with L     

An experimental study on ulcerative colitis as a potential target for probiotic therapy by Lactobacillus acidophilus with or without “olsalazine”

Traditional medical treatments for ulcerative colitis (UC) are still compromised by its adverse effects and not potent enough to keep in remission for long-term periods. So, new therapies that are targeted at specific disease mechanisms have the potential to provide more effective and safe treatments for ulcerative colitis. Probiotics is recently introduced as a therapy for ulcerative colitis. In the present study, Lactobacillus acidophilus was selected as a probiotic therapy to investigate its effects in oxazolone-induced colitis model in rats that mimics the picture in human. The rats were grouped (8 rats each) as normal control group (Group I), Group II served as untreated oxazolone-induced colitis, Group III oxazolone-induced colitis treated with probiotic L. acidophilus (1 × 10⁷ colony-forming units (CFU)/mL/day oral for 14 days), Group IV oxazolone-induced colitis treated with olsalazine (60 mg/kg/day oral for 14 days), Group V oxazolone-induced colitis treated with probiotic L. acidophilus and olsalazine in the same doses and duration. Disease activity index (DAI) was recorded, serum levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and intrleukin-6 (IL-6) was assessed as inflammatory markers and the histopathological picture of the colon of each rat was studied. Disease activity index (DAI) showed significant positive correlation with the elevated serum levels of CRP (r = 0.741, p < 0.05), TNF-α (r = 0.802, p < 0.05) and IL-6 (r = 0.801, p < 0.05). Treatment with either L. acidophilus (group III) or olsalazine (group IV) resulted in significant reduction in serum levels of CRP, TNF-α and IL-6, as well as disease activity index (DAI). Treatment with combination of L. acidophilus and olsalazine (group V) offered more significant reduction in serum levels of CRP, TNF-α, IL-6 and disease activity index (DAI) when compared to either group II (untreated group), group III (treated with L. acidophilus) or group IV (treated with olsalazine). So, it was concluded that L. acidophilus probiotic could be recommended as adjuvant therapy in combination with olsalazine to achieve more effective treatment for ulcerative colitis. For application in human, this needs to be verified in further clinical studies.     

Physiological impairment in mild COPD

Chronic obstructive pulmonary disease (COPD) is a common and often progressive inflammatory disease of the airways, alveoli and microvasculature that is both preventable and treatable. It is well established that smokers with mild airway obstruction, as spirometrically defined, represent the vast majority of patients with COPD, yet this population has not been extensively studied. An insidious preclinical course means that mild COPD is both underdiagnosed and undertreated. In this context, recent studies have confirmed that even patients with mild COPD can have extensive physiological impairment, which contributes to poor perceived health status compared with non‐smoking healthy controls. This review describes the heterogeneous pathophysiology that can exist in COPD patients with only mild airway obstruction on spirometry. It exposes the compensatory adaptations that develop in such patients to ensure that the respiratory system fulfils its primary task of maintaining adequate pulmonary gas exchange for the prevailing metabolic demand. It demonstrates that adaptations such as increased inspiratory neural drive to the diaphragm due to combined effects of increased mechanical loading and chemostimulation underscore the increased dyspnoea and exercise intolerance in this population. Finally, based on available evidence, we present what we believe is a sound physiological rationale for earlier diagnosis in this population.     

Serum cystatin C as an early predictor of acute kidney injury in preterm neonates with respiratory distress syndrome

Abstract

Preterm neonates with respiratory distress syndrome (RDS) are at increased risk of acute kidney injury (AKI). Our study aimed at determining whether serum cystatin C (sCysC) on day 3 of life (D3) can early predict AKI in preterm neonates with RDS. This prospective study was conducted on 75 preterm neonates; 50 with RDS and 25 without RDS. On D3, sCysC, serum creatinine (sCr) and blood urea nitrogen (BUN) were measured and estimated glomerular filtration rate (eGFR) was calculated. sCr and BUN levels were measured again on days 5 and 7. Neonates were evaluated for development of AKI during first week of life according to the modified pediatric RIFLE (pRIFLE) criteria. Thirteen neonates with RDS developed AKI (26%).There was no significant difference between RDS and control groups with respect to sCysC. RDS neonates with AKI had significantly higher sCysC than those without AKI (1.62?±?0.12 versus 1.16?±?0.09?mg/l; p?<?.001). RDS grade III–IV neonates had significantly higher sCysC than RDS grade I–II. There was a significant positive correlation between D3 sCysC and (D5 and D7 sCr and BUN). Receiver operating characteristic (ROC) curve showed that D3 sCysC can predict AKI in preterm neonates with RDS at a cutoff point of >1.3?mg/l with sensitivity of 92.30% and specificity of 96%. We conclude that neonates with RDS are at increased risk of AKI. sCysC on day 3 of life can predict AKI earlier than Cr and eGFR.     

Extended interval dosing of gentamicin in premature neonates ≤ 28‐week gestation

Aim: To evaluate an extended interval dosing (EID) regimen of gentamicin in neonates ≤28‐week gestation. Methods: In 2008, an EID regimen for gentamicin was introduced for all neonates admitted to the NICU in Calgary. The dosing interval was based on a 22 h level after the first dose of 5mg/kg. We conducted an observational study in 33 infants ≤28‐week gestation on the EID regimen from the first day of life and compared gentamicin peak and trough levels with a historical control of 34 infants who received gentamicin in a dose of 2.5 mg/kg every 24 h (TID, traditional interval dosing). Results: In the EID group, based on the 22 h level, dosing interval was 36 h in 20 neonates and 48 h in 13 neonates. All neonates, except one, achieved therapeutic peak and trough levels. Compared to the TID group, the EID group had higher peak levels (median 9.8 μg/mL vs. 4.6 μg/mL, p < 0.001) with no difference in trough levels. With target peak levels of 5–12 μg/mL and trough levels of <2 μg/mL, a higher proportion of neonates in the TID group would need dose adjustment. Conclusion: In neonates ≤ 28‐week gestation, an EID regimen from day one of life, using a single level 22 h after the first dose for dosing interval, achieves therapeutic peak and trough levels and more optimum peak levels as compared to a TID regimen.     

Cochlear implantation in developing countries

A cochlear implant program was started in Jeddah, Saudi Arabia, in September 1983. Three totally deaf adult patients have received implants so far, with encouraging results. The problems of cochlear implantation in developing countries are discussed with regard to the patient, team, and device. The rationale, stages, and future of the program are outlined.     

Pathology as it relates to ear surgery. VII. Tympanoplasty

The surgical anatomy and pathology of the middle ear have been reviewed in relation to tympanoplasty. The results of tympanoplasty in providing a disease-free and functional middle ear varies widely with the pathology involving the eardrum, ossicles, mucoperiosteum, mastoid air cells and eustachian tube. Post-tympanoplasty changes in the eardrum graft, ossicular grafts, and middle ear have been described in six cases which underwent surgery one to eleven years before death. Proper understanding of the pathophysiology of the different diseases of the middle ear is mandatory in planning tympanoplastic procedures. The causes of graft failure and of post-operative conductive hearing loss are discussed and the ways to avoid technical complications are emphasized.     

Factors influencing the participation of gastroenterologists and hepatologists in clinical research

Background  

Although clinical research is integral to the advancement of medical knowledge, physicians face a variety of obstacles to their participation as investigators in clinical trials. We examined factors that influence the participation of gastroenterologists and hepatologists in clinical research.