Effective Inhibition of TNF-α/mTOR Axis-Mediated Liver Inflammation and Fibrosis Induced by TAA Using a Combination of Metformin and Resveratrol in Association with the Inhibition of the Profibrotic Gene and Protein Expression

SUMMARY: The response of the immune system to harmful stimuli leads to inflammation, and the adverse effects of the toxic hepatitis chemical, thioacetamide (TAA) on the human body are well documented. This article investigated the degree of protection provided by the combined pleotropic drug, metformin (Met) and the plant polyphenolic and the antiinflammatory compound, resveratrol (Res) on liver tissue exposed to TAA possibly via the inhibition of the inflammatory cytokine, tumor necrosis factor-α (TNF-α) / mammalian target of rapamycin (mTOR) axis-mediated liver fibrosis, as well as amelioration of profibrotic gene and protein expression. Rats were either given TAA (200 mg/kg via intraperitoneal injection) for 8 weeks beginning at the third week (experimental group) or received during the first two weeks of the experiment combined doses of metformin (200 mg/kg) and resveratrol (20 mg/kg) and continued receiving these agents and TAA until experiment completion at week 10 (treated group). A considerable damage to hepatic tissue in the experimental rats was observed as revealed by tissue collagen deposition in the portal area of the liver and a substantial increase (p<0.0001) in hepatic levels of the inflammatory marker, tumor necrosis factor-α (TNF-α), as well as blood levels of hepatocellular injury biomarkers, alanine aminotransferase (ALT) and aspartate aminotransferase (AST). TAA also augmented hepatic tissue levels of the signalling molecule that promotes liver fibrosis (mTOR), and profibrogenic markers; alpha-smooth muscle actin (α-SMA) protein, tissue inhibitor of metalloproteinases-1 (TIMP-1) mRNA, and matrix metalloproteinase-9 (MMP-9) mRNA. All these parameters were protected (p≤0.0016) by Met+Res. In addition, a significant correlation was detected between liver fibrosis score and inflammation, liver injury enzymes, mTOR, and profibrogenesis markers. Thus, these findings suggest that Met+Res effectively protect the liver against damage induced by thioacetamide in association with the downregulation of the TNF-α/mTOR/fibrosis axis.

La respuesta del sistema inmunológico a estímulos dañinos conduce a la inflamación y los efectos adversos de la tioacetamida (TAA), una sustancia química tóxica para el hígado, están bien documentadas. Este artículo investigó el grado de protección proporcionado por el fármaco pleotrópico combinado metformina (Met), el polifenólico vegetal y el compuesto antiinflamatorio resveratrol (Res) en el tejido hepático expuesto a TAA, posiblemente a través de la inhibición de la citoquina inflamatoria, factor de necrosis tumoral α (TNF-α)/objetivo de la fibrosis hepática mediada por el eje de rapamicina (mTOR), así como mejora de la expresión de genes y proteínas profibróticas. Las ratas recibieron TAA (200 mg/kg mediante inyección intraperitoneal) durante 8 semanas a partir de la tercera semana (grupo experimental) o recibieron durante las dos primeras semanas del experimento dosis combinadas de metformina (200 mg/kg) y resveratrol (20 mg/kg) y continuaron recibiendo estos agentes y TAA hasta completar el experimento en la semana 10 (grupo tratado). Se observó un daño considerable al tejido hepático en las ratas experimentales, como lo revela el depósito de colágeno tisular en el área portal del hígado y un aumento sustancial (p<0,0001) en los niveles hepáticos del marcador inflamatorio, el factor de necrosis tumoral-α (TNF- α), así como los niveles sanguíneos de biomarcadores de lesión hepatocelular, alanina aminotransferasa (ALT) y aspartato aminotransferasa (AST). TAA también aumentó los niveles en el tejido hepático de la molécula de señalización que promueve la fibrosis hepática (mTOR) y marcadores profibrogénicos; proteína actina del músculo liso alfa (α- SMA), inhibidor tisular de las metaloproteinasas-1 (TIMP-1) mRNA y matriz metaloproteinasa-9 (MMP-9) mRNA. Todos estos parámetros fueron protegidos (p≤0.0016) por Met+Res. Además, se detectó una correlación significativa entre la puntuación de fibrosis hepática y la inflamación, las enzimas de lesión hepática, mTOR y los marcadores de profibrogénesis. Por lo tanto, estos hallazgos sugieren que Met+Res protege eficazmente el hígado contra el daño inducido por la tioacetamida en asociación con la regulación negativa del eje TNF-α/mTOR/fibrosis.

Infected Non-union of Tibia Treated with Ilizarov External Fixator: Our Experience

@#Introduction: Tibia is the most common long bone fractured due its vulnerable subcutaneous location and most often associated with acquired complications of delayed union or non-union due to infection. Amongst the various treatment options to treat them, the Ilizarov external fixator application is considered superior due to its multiple advantages. The objective of this study was to analyse the role of Ilizarov fixation in infected tibial non-union, as well as to assess bony union and associated functional outcomes. Materials and Methods: A retrospective review was conducted for the duration between 1st January 2005 to 31st December 2016. Total of fifty-one patients with tibial non-union associated with infection who treated with the Ilizarov fixator were included in the study. Patient records were reviewed for union of bone, bone and functional outcomes and complications. Results:The most common organism for infection was identified to be Staphylococcus Aureus. At the time of final follow-up all patients had achieved union except two, one of whom had to undergo amputation due to non-union and sepsis. Majority of the patients had an excellent score as per ASAMI grading system for bone and function results. The most common complication noted was pin track infections. Conclusion: In our experience, Ilizarov external fixator is better suited for infected non-union of tibia because it can provide a stable mechanical environment, bone transport, correct deformities, and enable weight bearing and hence we recommend its use for the same.

Ankle Arthrodesis using Ilizarov Ring Fixator: A Primary or Salvage Procedure? An Analysis of Twenty Cases

@#Introduction: Ankle arthrodesis using the Ilizarov technique provides high union rate with the added benefits of early weight-bearing, and the unique advantage of its ability to promote regeneration of soft tissue around the bone, including skin, muscle and neuro-vascular structures, and its versatility to allow correction of the position of the foot by adjusting the frame post-operatively as needed. We describe our experience with this technique and the functional outcomes in our patients. Materials and Methods: This retrospective study was conducted in 20 ankle fusion cases using the Ilizarov method between the years 2007 and 2017. We defined success in treatment by loss of preoperative symptoms and radiological union on plain radiographs of the ankle. Results: Fusion was achieved in all patients (100%). Immediate post-operative ambulation was with full weight bearing (FWB) in 16 (83%) of the participants and non-weight bearing (NWB) in 3 patients (17%). Postprocedure 11 patients (67%) of the participants who were full weight bearing required some form of support for walking for 2-3 weeks. Post-operatively three patients had pin tract infection requiring intravenous antibiotics. Radiological union took range of 6-12 weeks, mean union time was 8 weeks. Only one patient required bone grafting due to bone loss. Average follow-up period was 10-45 months. Conclusion: The Ilizarov technique has a high union rate and leads to general favourable clinical outcome and may be considered for any ankle arthrodesis but is especially useful in complex cases such as for revisions, soft-tissue compromise, infection and in patients with risk for non-union. Early weight bearing is an extra benefit.

Frequency and associated risk factors of recurrent diabetic ketoacidosis among Saudi adolescents with type 1 diabetes mellitus

To explore the frequency and associated risk factors of recurrent diabetic ketoacidosis [RDKA] among Saudi adolescents with type 1 diabetes mellitus [T1DM]. A cross-sectional study was conducted among 103 T1DM adolescents [aged 13-18 years, 57 males] who were hospitalized for diabetic ketoacidosis][DKA] between January 2013 and May 2014 at Prince Sultan Military Medical City [PSMMC], Riyadh, Kingdom of Saudi Arabia. The respondents were purposively, conveniently selected, and interviewed using a structured Arabic questionnaire including clinical information and demographics. Fifty-six participants had experienced one episode of DKA, 41 had 2 episodes, and 6 had >/=3 episodes. Compared with adolescents who had hemoglobin A1c [HbA1c] 9 HbA1c. Similarly, adolescents who stopped insulin and those with lipodystrophy at the injection site had a higher frequency of RDKA. Discontinuing insulin [67%] was the major reason for RDKA followed by infection [31%]. Among adolescents who discontinued insulin treatment, 31 [46.3%] gave no reason for stopping, 25 [37.3%] reported feeling sick, 7 [10.4%] gave a combination of reasons, and 4 [6%] reported a lack of supplies or other reasons. Regression analysis revealed that a higher HbA1c level and the presence of lipodystrophy were independent risk factors for RDKA. The frequency of RDKA was significantly greater in the T1DM adolescents with a higher HbA1c level, lipodystrophy, and those who had discontinued insulin treatment. Comprehensive multidisciplinary diabetes education should be offered to control modifiable risk factors in these patients

Predictive risk factors for fear of hypoglycemia and anxiety-related emotional disorders among adolescents with type 1 diabetes

To explore the fear of hypoglycemia [FOH] and anxiety-related emotional disorders and their risk factors among adolescents with type 1 diabetes mellitus [T1DM].Subjects and A cross-sectional study was conducted among 187 adolescents [aged 13-18 years; 92 males, 95 females] with T1DM at the Diabetes Treatment Center, Prince Sultan Military Medical City, Riyadh, Saudi Arabia, from June 2013 to February 2014. The participants were interviewed using FOH and Screen for Child Anxiety-Related Disorders [SCARED] scales. Females had significantly higher scores on all FOH and SCARED subscales compared to males. The mean scores for many subscales of FOH and SCARED were higher in the older age group [16-18 years], in those under multiple-dose injection [MDI] treatment [compared with the insulin pump treatment], and in those with a longer duration of T1DM. Similarly, significant differences were observed in those with high frequencies of hypoglycemia, passing out, hypoglycemia while asleep and awake, and hypoglycemia in front of friends and at school. Regression analysis revealed that higher age, female gender, MDI treatment, longer duration of T1DM, higher frequencies of hypoglycemia, passing out, hypoglycemia while asleep and awake, and hypoglycemia in front of friends and at school were the risk factors associated with the majority of the FOH and SCARED subscales. The behavior of the FOH subscale correlated with all the subscales of SCARED except the subscale of generalized anxiety disorder. Similarly, the FOH subscale of worry significantly correlated with all the subscales of SCARED. The strongest determinants of higher risk for the majority of the FOH and SCARED subscales were higher age, female gender, MDI treatment, longer duration of T1DM, higher frequency of hypoglycemia, passing out due to hypoglycemia, hypoglycemia while asleep and awake, and hypoglycemia in front of friends and at school

Factors Associated with Health-Related Quality of Life among Saudi Patients with Type 2 Diabetes Mellitus: A Cross-Sectional Survey

BACKGROUND: Diabetes mellitus (DM) is associated with high mortality, morbidity, poor general health, and loss of health-related quality of life (HRQOL). The objective of the study was to assess the factors associated with HRQOL among patients with type 2 diabetes mellitus (T2DM). METHODS: This was a cross sectional study conducted among 283 T2DM patients during June 2011 and September 2012 at a major tertiary hospital in Riyadh, Saudi Arabia. The respondents were purposively and conveniently selected according to their availability during their routine visit to the outpatient clinics and they were interviewed using the Arabic version of the Short-Form 36-item survey (SF-36) to assess the HRQOL. RESULTS: The mean age of the participants was 56.4+/-13.2 years. Around 63% (178) were males and 37% (105) were females. Glycosylated hemoglobin level was found to be significantly higher among female and HRQOL was higher among male. Respondents who were more than 50 years old had poor HRQOL than less than 50 years age group. Poor economic status, reported diabetic complications and longer duration of diabetes were significantly associated with poor HRQOL. The respondents treated with combination of therapies (oral medication plus insulin) indicated better HRQOL than patients with insulin therapy alone. Multivariate analysis indicated that gender, economic status (except subscale energy), and complications of DM (except subscale energy) as independent risk factor for HRQOL. CONCLUSION: Gender, economic status, and complication of DM were independent risk factors for majority of the subscales of HRQOL.

prevalence of smoking and its associated factors among military personnel in Kingdom of Saudi Arabia: a national study

The aim was to measure the prevalence of smoking and identify its potential predictors among military personnel in Kingdom of Saudi Arabia [KSA]. This cross-sectional study was carried out among military personnel in the five military regions of KSA between January 2009 and January 2011. The sample of 10,500 military personnel in the Saudi Armed Forces was equally divided among the five regions with a ratio 3:7 for officers and soldiers. A multistage stratified random sampling was used to recruit participants in the four services of the armed forces in the five regions. Information on sociodemographic characteristics with a detailed history of smoking was collected by means of a self-administered questionnaire. Bivariate analysis was used to identify the factors associated with smoking, and multiple logistic regression analysis to discover its potential predictors. About 35% of the sample was current smokers, with higher rates among soldiers. The eastern region had the highest rate [43.0%], and the southern region the lowest [27.5%]. Navy personnel had a higher risk of being current smokers [40.6%], and the air defense the lowest risk [31.0%]. Multivariate analysis identified working in the navy, and low income as positive predictors of current smoking, while residing in the southern region, older age, years of education, being married, and having an officer rank were negative [protective] factors. Smoking is prevalent among military personnel in KSA, with higher rates in the Navy and Air Force, among privates, younger age group, lower education and income, and divorced/widowed status. Measures should be taken to initiate programs on smoking cessation that involve changes in the environment that is likely to promote this habit

Assessment of health-related quality of life among adolescents with type 1 diabetes mellitus in Saudi Arabia

To evaluate the health-related quality of life [HRQoL] for adolescents with type 1 diabetes mellitus [T1DM]. A cross-sectional study was conducted among 214 adolescents [13-18 years] with T1DM at the Diabetes Treatment Center, Prince Sultan Military Medical City, Riyadh, Saudi Arabia from June to September 2013. Respondents were selected by their availability during routine visits to outpatient clinics, and interviewed using the Arabic translated version of the Pediatric Quality of Life Inventory 3.0 Diabetes Module [PedsQL 3.0 DM] independently. Female gender, multiple daily injection [MDI], longer duration of T1DM [>7 years], diabetic ketoacidosis [DKA] and adolescents with >7 HbA1c level had at least one poor HRQoL outcome. Multivariate linear regression analysis showed that age, treatment type [MDI], DKA, and >7 HbA1c were independent influencing factors for subscale diabetes symptoms, whereas >7 HbA1c was the independent influencing factor for treatment barriers and overall HRQoL. The DKA was the independent influencing factor for the subscale of worry, and female gender was the independent influencing factor for the subscale of communication. Female gender, age, treatment type, >7 HbA1c, and DKA are the strongest determinants for lower HRQoL for at least one subscale of the PedsQL 3.0 DM

Does routine histopathological examination of gallbladder after simple cholecystectomy add additional value?

Cholecystectomy for gallbladder stone disease is a common surgical procedure. Gallbladder carcinoma is a rare malignancy with poor prognosis, which has been linked in some studies to pre-existing gall stone disease. The current practice is to send all gallbladder specimens after cholecystectomy for histopathological examination. This adds additional workload on the pathologists. To determine the necessity of routine histopathological examination of gallbladder specimens following simple cholecystectomy. Aseer Central Hospital, Abha, Saudi Arabia. Retrospective cohort study. Patients who had cholecystectomy for gallstone disease from April 2010 to March 2012 were included. Operative notes, histopathological reports and final diagnoses were reviewed. The study included 803 patients who had simple cholecystectomy. Three of these patients were found to have gallbladder carcinoma, two females and one male. Dense adhesions were encountered in all malignant cases necessitating conversion from laparoscopic to open cholecystectomy in one case. Macroscopic examination revealed a thickened gallbladder in all three patients; two patients had mucosal papillary lesions and one patient had polypoidal projection and mucosal ulcerations. These findings were confirmed by the pathologist. On microscopic examination, two patients had adenocarcinoma while one patient had neuroendocrine tumor. Selective approach for sending gallbladder specimens after cholecystectomy seems justifiable with no compromise on detection of incidental gallbladder cancer. This approach would lead to a reduction of workload on the pathologist.

Patterns of diseases and preventive measures among domestic hajjis from Central, Saudi Arabia [complete republication]

To identify the occurrence of upper respiratory tract infections [URTI], diarrheal diseases and trauma during the Hajj season, and the practice of some preventive measures by pilgrims. A cohort study during November and December 2009 among hajjis registered while visiting Primary Health Care Centers of Riyadh, Kingdom of Saudi Arabia to get mandatory meningococcal meningitis vaccination. On return from hajj, hajjis were contacted on telephone to collect information on occurrence of URTI and diarrhea along with other associated activities in Hajj. Out of 1507 hajjis, 54.7% developed symptoms; 97% reported upper respiratory tract symptoms, and 9.3% reported diarrheal symptoms. Those <40 years of age were more likely to develop an URTI. The incidence of diarrheal diseases or trauma was not statistically associated with age. No statistical difference for educational level was found for URTI or trauma, but there was a statistically significant difference for diarrheal diseases. There was no statistical difference for nationality in relation to diarrheal diseases and trauma, but there was a statistically significant difference for URTI. There was a statistically significant difference of URTI between those pilgrims who used the face mask most of the time and those who used it sometimes. Upper respiratory tract infections is a common health problem among studied domestic hajjis. Generally, there is room for improvement in the adoption of preventive measures by hajjis; and there is still limited information on the use of facemasks in spite of the fact that using it significantly decreases the risk for URTI

Assessment Of Students’ Perceptions Towards E-Learning Management System (E-LMS) In A Malaysian Pharmacy School: A Descriptive Study

The study aims to evaluate students’ perceptions towards e-Learning Management System (e-LMS) in pharmacy education. A cross-sectional survey was conducted among all undergraduates enrolled at School of Pharmaceutical Sciences, Universiti Sains Malaysia. A pre-validated questionnaire consisting of two domains (demographic characteristics and students’ perception regarding the use of e-LMS) was used for data collection. Descriptive statistics were used to describe the demographic characteristics of the study respondents. Chi Square test was used to measure association between the study variables. All analysis was performed by using Predictive Analytical Software (PASW) v. 18. A total of 315 students completed the survey questionnaire with a response rate of 57.6%. Majority of the students (61.0%) accessed e-LMS to acquire lecture notes for their studies, followed by 53.3% have used e-LMS for the preparation of the assignments. Seventy eight percent of the respondents agreed that e-LMS is very useful and felt that e-LMS is making their studies easier. However, 50% of students claimed that poor network connection at the campus is a major barrier in accessing e-LMS. Moreover, 48% of the respondents disagreed that e-LMS should be taken into account as an assessment criterion for students’ grading. Students are found to be frequently engaged in using e-LMS and believed that online based learning is enhancing their academic performances. Nevertheless, students still prefer hybrid teaching methodologies than choosing traditional system or e-learning as an alone entity.

Patterns of diseases and preventive measures among domestic hajjis from central, Saudi Arabia

To identify the occurrence of upper respiratory tract infections [URTI], diarrheal diseases and trauma during the Hajj season, and the practice of some preventive measures by pilgrims. A cross-sectional study during November and December 2009 among hajjis registered while visiting Primary Health Care Centers of Riyadh, Kingdom of Saudi Arabia to get mandatory meningococcal meningitis vaccination. On return from hajj, hajjis were contacted on telephone to collect information on occurrence of URTI and diarrhea along with other associated activities in Hajj. Out of 1507 hajjis, 54.7% developed symptoms; 97% reported upper respiratory tract symptoms, and 9.3% reported diarrheal symptoms. Those <40 years of age were more likely to develop an URTI. The incidence of diarrheal diseases or trauma was not statistically associated with age. No statistical difference for educational level was found for URTI or trauma, but there was a statistically significant difference for diarrheal diseases. There was no statistical difference for nationality in relation to diarrheal diseases and trauma, but there was a statistically significant difference for URTI. There was a statistically significant difference of URTI between those pilgrims who used the face mask most of the time and those who used it sometimes. Upper respiratory tract infections is a common health problem among studied domestic hajjis. Generally, there is room for improvement in the adoption of preventive measures by hajjis; and there is still limited information on the use of facemasks in spite of the fact that using it significantly decreases the risk for URTI