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Postmenopausal osteoporosis is characterized by rapid bone loss occurring in the post-menopausal period. The bone loss predominantly involves the trabecular bone and is brought about by an imbalance between the bone remodeling process which can be influenced by factors that could cause or contribute to osteoporosis. Pro-inflammatory cytokines (Il-1β, Il-6, IL-8 and TNF-α) have been implicated in the regulation of bone cells and play a critical role in bone remodeling. They act both directly and indirectly to increase bone resorption, and/or inhibit bone formation. The aim of the study is to determine whether pro-inflammatory cytokines correlate with bone turnover markers (BTM) in a cohort of Saudi post-menopausal women with or without osteoporosis and which BTMs will correlate with PTH and Vitamin D for use in osteoporosis diagnosis. The study is composed of 100 post-menopausal patients and 100 controls aged around 50 years. Serum concentrations of pro-inflammatory and BTMs as well as PTH and vitamin D were determined by ELISA, Luminex and electrochemiluminescence. Serum calcium, phosphorus, glucose, and lipid profile were measured by using a chemical analyzer. There was a significant increase in the levels of pro-inflammatory cytokines, PTH, CTx, and glucose. A significantly lower vitamin D and osteocalcin levels were observed in subjects with osteoporosis than those without. No significant differences were recorded in the circulating lipid profile between groups. The present study proved that the pro-inflammatory cytokines accelerate the bone loss in postmenopausal women.

Postmenopausal osteoporosis is characterized by rapid bone loss occurring in the post-menopausal period. The bone loss predominantly involves the trabecular bone and is brought about by an imbalance between the bone remodeling process which can be influenced by factors that could cause or contribute to osteoporosis. Pro-inflammatory cytokines (Il-1β, Il-6, IL-8 and TNF-α) have been implicated in the regulation of bone cells and play a critical role in bone remodeling. They act both directly and indirectly to increase bone resorption, and/or inhibit bone formation. The aim of the study is to determine whether pro-inflammatory cytokines correlate with bone turnover markers (BTM) in a cohort of Saudi post-menopausal women with or without osteoporosis and which BTMs will correlate with PTH and Vitamin D for use in osteoporosis diagnosis. The study is composed of 100 post-menopausal patients and 100 controls aged 50 years and above. Serum concentrations of pro-inflammatory and BTMs as well as PTH and vitamin D were determined by ELISA, Luminex and electrochemiluminescence. Serum calcium, phosphorus, glucose, and lipid profile were measured by using a chemical analyzer. There was a significant increase in the levels of pro-inflammatory cytokines, PTH, CTx, and glucose. A significantly lower vitamin D and osteocalcin levels were observed in subjects with osteoporosis than those without. No significant differences were recorded in the circulating lipid profile between groups. The present study proved that the pro-inflammatory cytokines accelerate the bone loss in postmenopausal women.

Background: The over-all age-adjusted prevalence of diabetes mellitus type 2 (DMT2) in Saudi Arabia is unprecedented at 31%. Aggressive measures should be done to curb down increasing incidence. In this prospective 6-month study we aim to determine whether a self-monitoring, life-style modification program that includes increased sunlight exposure confer improvement in vitamin D status and health benefits among adult Saudi overweight and obese patients with varying glycemic status., Methods: A total of 150 overweight and obese Saudi adults with varying glycemic status aged 30-60 years were included in this study. They were divided into 3 groups (Non-DMT2, Pre-diabetes and DMT2). Baseline anthropometrics and blood glucose were taken at baseline and after 6 months. Fasting blood sugar, lipid profile, calcium, albumin and phosphate were measured routinely. Serum 25(OH) vitamin D was measured using standard assays. Within the time period they were instructed to reduce total intake of fat, increased fiber intake and increase sun exposure., Results: In all groups there was a significant improvement in vitamin D levels as well as serum triglycerides, LDL- and total cholesterol. However, a significant increase in serum glucose levels was noted in the non-DMT2 group, and a significant decrease in HDL-cholesterol in both non-DMT2 and pre-diabetes group. In the pre-diabetes group, 53.2% were able to normalize their fasting blood levels after 6 months, with 8.5% reaching the DMT2 stage and 38.3% remaining pre-diabetic. In all groups there was a significant increase in the prevalence of hypertension., Conclusion: Improving vitamin D status with modest lifestyle modifications over a short-period translates to improvement in lipid profile except HDL-cholesterol among overweight and obese Saudi adults, but not BMI and blood pressure. Findings of the present study merit further investigation as to whether full vitamin D status correction can delay or prevent onset of DMT2.

Objectives: If they do not respond to other treatments, patients with Budd-Chiari syndrome are potential candidates for a liver transplant. Timing for transplant is controversial; however, before other systems deteriorate, early intervention in relatively stable patient may improve the outcome and survival of these patients., Materials and Methods: Six patients (2 women and 4 men) had Budd-Chiari syndrome (1.2%) among 475 patients who had undergone a liver transplant at our center between 2001 and 2012. Imaging modalities including duplex ultrasound, abdominal computed tomography angiography, and hematologic evaluation were part of our routine diagnostic work-up. Although we perform mostly living-donor liver transplants, these patients received a liver transplant from a deceased donor, because there was not enough evidence to justify a living-donor liver transplant. We thought that not replacing the caval vein might negatively influence the outcome. Postoperatively, these recipients were started on a heparin infusion and triple therapy immunosuppression; only then was warfarin introduced as long-term anticoagulant., Results: Two patients died, 1 from uncontrollable bleeding and disseminated intravascular coagulopathy, and the other died in the intensive care unit after 5 months because of multiorgan failure and sepsis. One patient had portal vein thrombosis 9 months after the liver transplant; the other patient needed a liver retransplant after 5 years owing to liver failure, secondary to chronic rejection. Graft survival rate was 75%, and patient survival rate was 66.6%., Conclusions: This is the first article from Saudi Arabia to describe the outcome of a liver transplant in this subgroup of patients with Budd-Chiari syndrome. Treatment of Budd-Chiari syndrome follows a therapeutic algorithm that should start with anticoagulation and may end up with liver transplant; however, it should be considered early if other treatments fail.

While moderate to severe vitamin D deficiency is prevalent in Saudi Arabia, skeletal effects associated with this deficiency are not common in this population. In this interventional study we measured the effects of improving vitamin D status on bone biochemical markers in overweight and obese adult Saudis. A total of 47 volunteers (21 males, 26 females) out of the initial 95 subjects were given verbal advice to expose themselves to sunlight for 5-30 min twice weekly and were encouraged to increase their intake of vitamin D-rich foods. Serum 25(OH)D, osteocalcin, and type 1 collagen cross-linked C-telopeptide (CTx), were measured at baseline and after one year. A significant decrease in the prevalence of vitamin D deficiency was observed (44% to 27%) after one year follow-up (p = 0.025). Also, a parallel significant increase in osteocalcin and a decrease in CTX and osteoprotegerin were observed. The results suggest that a modest increase in vitamin D levels among overweight and obese subjects through the promotion of lifestyle changes for one year have marginal effects in bone turnover markers as well as obesity itself.

Background: Little or no research has determined the effect of vitamin D3 supplementation in conjunction with pharmacological and non-pharmacological approaches in the diabetes mellitus type 2 (DMT2) patients. The objective of this study was to determine the effect of vitamin D3 supplementation in a cohort of Saudi DMT2 population on diet, insulin and/or different oral hypoglycemic agents and compare them with a non-DMT2 control cohort., Methods: A total of 499 randomly selected Saudi subjects divided into 8 groups [Non-DMT2 Control = 151; Rosiglitazone alone = 49; Diet = 15; Insulin alone = 55; Insulin + Orals = 12; Metformin alone = 121; Oral agents combination = 37; Sulphonylurea alone = 59] were included in this 12-month interventional study. All DMT2 patients were given 2000 IU vitamin D3 daily, while the control group received none but were advised to increase sun exposure. Anthropometrics, glucose, lipid profile and 25-hydroxyvitamin D (25-OHVitD) were measured at baseline, 6 and 12 months., Results: Circulating 25-OHVitD concentrations improved in all patient groups. The metformin group showed the highest change in circulating vitamin D levels both at 6 months (62.6%) and 12 months (50.6%) as compared to baseline (p < 0.001). No significant changes were observed in the BMI and glucose in any of the DMT2 groups. In contrast, the insulin + oral agents group showed more significant improvements in the metabolic profile, which included triglycerides and total cholesterol, as well as systolic blood pressure and HDL-cholesterol in males. Also, significant decreases in triglycerides were observed in the rosiglitazone and insulin + oral hypoglycemic agent groups both at 6 and 12 months of supplementation (both p-values <0.001)., Conclusion: While in all DMT2 groups circulating levels of 25-OHVitD increased after supplementation, in DMT2 patients on insulin in combination with other drugs benefitted the most in improving cardiovascular risk. Metformin improves 25-hydroxyvitamin D levels but did not seem to confer other added cardiometabolic benefits.

Background: Low grade chronic inflammation is observed in patients with type 2 diabetes mellitus (T2DM). Endotoxin derived from gut bacteria may act as a potent inflammatory stimulant. Probiotics, which are believed to contain health promoting live microorganisms, may influence circulating endotoxin levels. Ingestion of live probiotic cultures may alter gut microbiota in a beneficial manner to reduce inflammation; no information is available whether or not they do so in patients with T2DM. Therefore, the aim of this study is to characterize the beneficial effects of probiotics on circulating endotoxin levels and other biomarkers related to systemic low-grade inflammation in patients with T2DM., Methods: One hundred and twenty consenting adult Saudi T2DM patients (naïve or newly diagnosed and without co-morbidities) will be enrolled in this clinical trial and randomized to receive daily placebo or probiotics (Ecologic®Barrier) for 26 weeks in a double-blind manner. Inflammatory and metabolic markers will be measured and fecal samples analyzed. Measurements/samples will be obtained at baseline and after 4, 8, 12/13 and 26 weeks of treatment., Discussion: It is expected that the probiotic product will induce beneficial changes in gut microbiota, reduce the systemic inflammatory state through altering systemic endotoxin levels and, as such, reduce the systemic inflammatory response observed in T2DM subjects., Trial Registration: ClinicalTrials.gov Identifier: NCT01765517.

Recent studies in the Middle East have shown an increased incidence of vitamin D deficiency across this region of year-round sunlight. There is scarcity of information, however, as to the levels of 1,25-dihydroxyvitamin D [1,25(OH)2D], the active form of vitamin D, and its associations with cardiometabolic parameters in an Arab cohort and this study aims to fill this gap. In a cross-sectional study, 33 male and 43 female (22 children and 54 adults, total 76) Saudis with previously established low levels of serum 25-hydroxyvitamin D [25(OH)D] (<50 ng/ml or 20 nmol/l) were recruited. Anthropometrics were obtained and fasting blood samples were taken for a routine measurement of glucose, lipid profile, calcium, and albumin, while serum 25(OH)D, 1,25-(OH)2D, and intact PTH were quantified using specific ELISAs. Serum calcium, intact PTH, and 1,25(OH)2D were all within the normal range in both children and adults in both genders. In all subjects, serum 1,25(OH)2D was not associated with intact PTH, while circulating 1,25(OH)D inversely correlated with systolic blood pressure (p=0.01) and waist circumference (p=0.04). Thus, vitamin D deficient Saudi children and adults with normal levels of 1,25-(OH)2D also had normal circulating calcium and PTH. This study suggests that local cutoffs should be set that will be of clinical significance in the identification of those at true risk for harder end-points, such as secondary hyperparathyroidism and bone-related diseases., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Hypovitaminosis D has been associated with an increased prevalence of Type 2 diabetes mellitus (DMT2) and metabolic syndrome manifestations. The purpose of this study was to examine the association between 25-hydroxy-vitamin D (25-OH-VitD) levels and indices of insulin resistance (IR), including adipocytokines, in a Saudi population with or without DMT2., Subjects and Methods: A total of 266 subjects (153 DMT2 and 113 healthy controls) aged 26-80 yr were randomly selected from the existing Biomarkers Screening in Riyadh Program (RIYADH Cohort). Subjects were assessed clinically, anthropometry was performed, morning blood chemistries, including fasting glucose (FG), triglycerides, total cholesterol, LDL cholesterol (LDL-C), and HDL cholesterol were obtained. Homeostasis model assessment of IR (HOMA-IR) was calculated, and serum 25-OH-VitD, leptin, adiponectin, resistin, insulin, high sensitivity CRP (hsCRP), and tumor necrosis factor α concentrations were measured using specific assays., Results: In DMT2 subjects, negative correlations between 25-OH-vitD and body mass index (BMI), FG, insulin, HOMA-IR, cholesterol, LDL-C, and hsCRP were observed, while a positive correlation between 25-OH-VitD and adiponectin was detected. The later remained significant after controlling for BMI. Interestingly, only weak and nonsignificant associations between 25-OH-VitD and metabolic parameters were observed in the control group, whereas, when the entire population was examined, negative correlations were evident primarily between 25-OH-VitD and FG, HOMA-IR, total cholesterol, LDL-C. These associations remained significant after controlling for BMI., Conclusions: These results suggest that hypovitaminosis D associations with metabolic disturbances are accentuated in DMT2. The BMIindependent positive correlation between 25-OH-VitD and adiponectin suggests a potential role for this adipocytokine as a link between 25-OH-VitD and IR in patients with DMT2.

Background: Coffee and tea consumption was hypothesized to interact with variants of vitamin D-receptor polymorphisms, but limited evidence exists. Here we determine for the first time whether increased coffee and tea consumption affects circulating levels of 25-hydroxyvitamin D in a cohort of Saudi adolescents., Methods: A total of 330 randomly selected Saudi adolescents were included. Anthropometrics were recorded and fasting blood samples were analyzed for routine analysis of fasting glucose, lipid levels, calcium, albumin and phosphorous. Frequency of coffee and tea intake was noted. 25-hydroxyvitamin D levels were measured using enzyme-linked immunosorbent assays., Results: Improved lipid profiles were observed in both boys and girls, as demonstrated by increased levels of HDL-cholesterol, even after controlling for age and BMI, among those consuming 9-12 cups of coffee/week. Vitamin D levels were significantly highest among those consuming 9-12 cups of tea/week in all subjects (p-value 0.009) independent of age, gender, BMI, physical activity and sun exposure., Conclusion: This study suggests a link between tea consumption and vitamin D levels in a cohort of Saudi adolescents, independent of age, BMI, gender, physical activity and sun exposure. These findings should be confirmed prospectively.

Background: Vitamin D deficiency has been associated with impaired human insulin action, suggesting a role in the pathogenesis of diabetes mellitus type 2 (T2DM). In this prospective interventional study we investigated the effects of vitamin D3 supplementation on the metabolic profiles of Saudi T2DM subjects pre- and post-vitamin D supplementation over an 18-month period., Methods: T2DM Saudi subjects (men, N = 34: Age: 56.6 ± 8.7 yr, BMI, 29.1 ± 3.3 kg/m2; women, N = 58: Age: 51.2 ± 10.6 yr, BMI 34.3 ± 4.9 kg/m2;) were recruited and given 2000 IU vitamin D3 daily for 18 months. Anthropometrics and fasting blood were collected (0, 6, 12, 18 months) to monitor serum 25-hydroxyvitamin D using specific ELISA, and to determine metabolic profiles by standard methods., Results: In all subjects there was a significant increase in mean 25-hydroxyvitamin D levels from baseline (32.2 ± 1.5 nmol/L) to 18 months (54.7 ± 1.5 nmol/L; p < 0.001), as well as serum calcium (baseline = 2.3 ± 0.23 mmol/L vs. 18 months = 2.6 ± 0.1 mmol/L; p = 0.003). A significant decrease in LDL- (baseline = 4.4 ± 0.8 mmol/L vs. 18 months = 3.6 ± 0.8 mmol/L, p < 0.001] and total cholesterol (baseline = 5.4 ± 0.2 mmol/L vs. 18 months = 4.9 ± 0.3 mmol/L, p < 0.001) were noted, as well as a significant improvement in HOMA-β function (p = 0.002). Majority of the improvements elicited were more prominent in women than men., Conclusion: In the Saudi T2DM population receiving oral Vitamin D3 supplementation (2000 IU/day), circulating 25-hydroxyvitamin D levels remained below normal 18 months after the onset of treatment. Yet, this "suboptimal" supplementation significantly improved lipid profile with a favorable change in HDL/LDL ratio, and HOMA-β function, which were more pronounced in T2DM females.

Biochemical bone turnover markers (BTMs) provide important information on the diagnosis, therapy and monitoring of metabolic bone diseases. They are evident before measurable changes in bone mineral density (BMD) take place. A total of 35 adult Saudi patients (23 males; 12 females) with type 2 diabetes and diagnosed to be vitamin D deficient were recruited in this prospective study. Here we investigated the effects of gender, season, and vitamin D status on bone biochemical markers of bone remodeling. Anthropometry and blood samples were collected at different intervals. Metabolic parameters and bone biomarkers were measured routinely and by ELISA. Both males and females had a significant increase in their vitamin D status over time, but no significant changes in the bone biomarkers were observed in females. In males there was a significant increase in circulating levels of corrected calcium and OPN (p = 0.004 and 0.01 respectively) and a significant decrease in crosslaps (p = 0.005). In all subjects there was a modest but significant positive relationship between vitamin D status and OC (R = 0.34; p = 0.04). In conclusion, our study demonstrates that changes in bone remodeling markers are affected by season, gender, and possibly vitamin D status. This gender difference may well reflect the physiologic pathway responsible for the higher peak bone mass achieved in males compared to females.

Background: Accumulating evidence suggests an increased prevalence of vitamin D deficiency in the Middle East. In this context, we aimed to determine whether the prevalence of vitamin D deficiency is related to degree of physical activity and sun exposure among apparently healthy Saudi children and adolescents, a little studied population., Methods: A total of 331 Saudi children aged 6-17 years (153 boys and 178 girls) were included in this cross sectional study. Levels of physical activity and sun exposure were determined using a standard questionnaire. Anthropometry, serum calcium and 25-(OH) vitamin D were analyzed., Results: All subjects were vitamin D deficient, the majority being moderately deficient (71.6%). Age was the single most significant predictor affecting 25 (OH) Vitamin D levels, explaining 21% of the variance perceived (p = 1.68 x 10-14). Age-matched comparisons revealed that for groups having the same amount of sun exposure, those with moderate or are physically active will have higher levels of vitamin D status, though levels in across groups remained deficient., Conclusion: Vitamin D deficiency is common among Saudi children and adolescents, and is influenced by both sun exposure and physical activity. Promotion of an active outdoor lifestyle among Saudi children in both homes and schools may counteract the vitamin D deficiency epidemic in this vulnerable population. Vitamin D supplementation is suggested in all groups, including those with the highest sun exposure and physical activity.

Unlabelled: Vitamin D deficiency has been linked to several chronic diseases in adults. Studies focusing on children and adolescents, however, are limited. In this randomized cross-sectional study, we aimed to determine the prevalence of vitamin D deficiency and its relationship with childhood obesity and dietary calcium intake among a population of healthy urban Saudi children and adolescents. To achieve this, 331 randomly selected Saudi children (53.8% females and 46.2% males) aged 6-17 years were included. Demographic, medical, and dietary information were collected; anthropometrics were measured. Levels of serum fasting glucose, lipid profile, 25(OH) D, and for albumin corrected calcium were analyzed. Vitamin D deficiency was noted in all subjects, with girls having significantly lower vitamin D levels than boys. Mean calcium intake was found to be 60% of the required dietary allowance (RDA), while the mean vitamin D intake was 23% of RDA. Vitamin D status and calcium intake were comparable in both normal and overweight/obese children and adolescents. Vitamin D status was highest among children who had calcium intake >800 mg/day. In adolescents there was insignificant but decreasing trend in BMI, which was observed to be highest among those whose calcium intake was <250 mg/day and lowest among those taking >800 mg/day., Conclusion: results from this study suggest the importance of vitamin D fortification and increased dietary calcium in the Saudi diet to meet RDA requirements and avoid onset of vitamin D deficiency-related diseases in Saudi children and adolescents.

Numerous cross-sectional studies have noted significant negative associations between circulating levels of 25-hydroxyvitamin D and cardiometabolic risk factors, highlighting potential extraskeletal functions of this sterol hormone. Prospective studies, however, have been limited; and hence, no cause-and-effect relations can be inferred. This study aims to determine whether vitamin D status correction can reverse already established manifestations of the metabolic syndrome (MetS). A total of 59 adult nondiabetic, overweight, and obese Saudis (31 male, 28 female) were prospectively enrolled in this 1-year interventional study. Anthropometry and biochemical evaluation were performed, including determination of serum 25-hydroxyvitamin D, calcium, and phosphorous concentrations, as well as fasting blood glucose and lipid profile. Subjects were advised to regularly expose themselves to sunlight and increase intake of vitamin D-rich foods. All measurements were repeated 6 and 12 months later. At the initial baseline visit, the prevalence of both low high-density lipoprotein cholesterol and hypertension was significantly increased among patients with 25-vitamin D deficiency (P < .05), even after adjusting for sex and body mass index. Overall prevalence of MetS patients by the modified National Health and Nutrition Examination Survey Adult Treatment Panel III definition decreased from 25.2% to 13.0%; and this was largely due to a parallel decrease in the prevalence of low high-density lipoprotein cholesterol, triglycerides, and hypertension. Optimization of vitamin D status through sun exposure and increased intake of a vitamin D-rich diet can lead to an improved cardiometabolic profile, offering a promising nonpharmacologic approach in the prevention of MetS manifestations., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose:   Seasonal variations in circulating vitamin D levels provide vital information as to the most appropriate time to either start or increase vitamin D supplementation to maintain optimal vitamin D levels. In this follow-up study, we determined seasonal differences in serum 25(OH)-vitamin D (25(OH)D) levels, as well as parallel changes in metabolic parameters, in a cohort of adult, overweight and obese Saudis., Methods:   A total of 121 adult, overweight, obese, and consenting Saudis aged 18-70 years were randomly recruited from four Primary Health Care Centers in Riyadh, Saudi Arabia. They were divided according to the season when baseline measurements were made [74 summer (April-October); 47 winter (November-March)]. Anthropometrics were obtained, and fasting blood samples were taken at baseline and every 3 months for 1 year. Fasting blood glucose, corrected calcium levels, and lipid profiles were measured routinely. Serum 25(OH)-vitamin D was quantified using a specific enzyme-linked immunosorbent assay (ELISA)., Results:   Age- and BMI-matched mean 25(OH)-vitamin D levels from the winter group were significantly higher than those of the summer group (P < 0·001). In both groups, HDL-C levels improved significantly as 25(OH)-vitamin D levels increased with subsequent follow-ups, even after adjusting for age, gender and BMI (P < 0·001)., Conclusion:   Seasonal differences in serum 25(OH)-vitamin D levels in Saudi Arabia are counterintuitive, with circulating levels being higher during the winter than the summer season. Increased vitamin D supplementation is thus recommended to maintain optimal serum 25(OH)-vitamin D levels during the summer season., (© 2012 Blackwell Publishing Ltd.)

Objective: Biliary tract carcinomas are uncommon but highly fatal malignancies. Unfortunately, most cases are ineligible for surgery at diagnosis with chemotherapy being the mainstay of treatment. The aim of this Phase II study was to evaluate the efficacy and safety of a biweekly outpatient regimen of gemcitabine plus oxaliplatin in cases of advanced biliary tract carcinomas., Methods: Forty patients with advanced, chemotherapy-naïve biliary tract carcinomas were enrolled in the study between December 2005 and November 2009. All patients received the gemcitabine plus oxaliplatin treatment protocol as follows: gemcitabine 1000 mg/m(2) (30 m infusion) followed by oxaliplatin 85 mg/m(2) (2 h infusion) on days 1 and 15 of a 28-day cycle. The primary endpoint was the tumor control rate. Efficacy and safety analyses were done by intention to treat., Results: The objective response rate was 27.5% and the tumor control rate was 65%. The median progression-free survival was 4 months and the median overall survival was 12 months. The tumor control was translated into a significant prolongation in overall survival. The regimen was generally well tolerated; Grade 3-4 toxicities were recorded in 25% of the patients with neutropenia being the most common (17.5%); Grade 3 sensory neuropathy was uncommon (2.5%)., Conclusions: The study provides further evidence for the activity of gemcitabine plus oxaliplatin combination as a first-line treatment for advanced biliary tract carcinomas. This combination can be given safely as a convenient biweekly outpatient regimen.

Background: Liposuction is a surgical technique to remove excess fat deposits from specific areas of the body. Purpose of this study is to determine how far large volume liposuction is safe and effective., Methodology: From July 2003 to December 2005, 60 female patients had liposuction of different areas of the body as waist, hips, buttocks, thighs, and knees. Their mean age was 30.6 +/- 15.4 years old. A standard liposuction technique was done by using a tumescent infiltration formula. The average amount of infusate was 3000 cc, with an average aspirate amount of 6000 cc. Pre-operative anthropometric measurements as weight, height, body mass index, areas to be liposuctioned in addition to pre-operative hematological investigations as complete blood picture, blood sugar, liver function tests, blood urea, serum creatinine, and serum cholesterol were done., Results: The results were evaluated with preoperative and postoperative photographs. Postoperative anthropometric measurements and hematological investigations were done at 6th week, and 4th month after surgery. The rate of complications was low and relatively minor in nature. No major complications were presented. Minor complications have occurred as skin irregularities (20%), Seroma (15%), Garment pressure sore (10%), Cutaneous hyper-pigmentation (5%)., Conclusion: Large-volume liposuction can be performed safely and it can produce desirable morphological and hematological changes.

This study covered 40 patients (22 females and 18 males) suffering from post-burn hand deformities admitted to Assiut University Hospital and Luxor International Hospital (Egypt) from June 2004 to May 2006. Their ages ranged between 4 and 45 yr (mean, 24.5 yr). They presented a variety of post-burn hand deformities, e.g. dorsal hand contracture (14 cases), volar contracture (10 cases), first web space contracture (3 cases), post-burn syndactyly (2 cases), wrist deformity (3 cases), skin and tendon affection (2 cases), and complex deformity (6 cases). All the patients underwent a variety of surgical procedures specific to the individual post-burn hand deformity. Post-operative splinting of the hand for 10 days was performed in patients with skin graft to prevent recontracture. The post-operative physiotherapy programme started in the second week in order to achieve good functional results. The follow-up period ranged from 6 to 20 months. The results were satisfactory in most of the cases as regards the quality of coverage, which was achieved in the majority of cases. In one case there was partial loss of the skin graft, which healed by secondary intention; full range of motion was achieved in most patients, but not those with joint affections. On the basis of our results, we can conclude that the management of post-burn hand deformities depends on several factors. Initial treatment of the burned hand is of great importance for the prevention of secondary deformities. In secondary burn management the first step is the release of the contracture, which should be complete and include all contracted structures. The second step is the proper selection of methods of coverage for resultant defects, using either skin grafts or flaps depending on the presence of exposed tendons, nerves, or joints. The third step in order to obtain a very good function is the activation of an intensive physiotherapy programme immediately after the operation.

This study covered 40 patients (22 females and 18 males) suffering from post-burn hand deformities admitted to Assiut University Hospital and Luxor International Hospital (Egypt) from June 2004 to May 2006. Their ages ranged between 4 and 45 yr (mean, 24.5 yr). They presented a variety of post-burn hand deformities, e.g. dorsal hand contracture (14 cases), volar contracture (10 cases), first web space contracture (3 cases), post-burn syndactyly (2 cases), wrist deformity (3 cases), skin and tendon affection (2 cases), and complex deformity (6 cases). All the patients underwent a variety of surgical procedures specific to the individual post-burn hand deformity. Post-operative splinting of the hand for 10 days was performed in patients with skin graft to prevent recontracture. The post-operative physiotherapy programme started in the second week in order to achieve good functional results. The follow-up period ranged from 6 to 20 months. The results were satisfactory in most of the cases as regards the quality of coverage, which was achieved in the majority of cases. In one case there was partial loss of the skin graft, which healed by secondary intention; full range of motion was achieved in most patients, but not those with joint affections. On the basis of our results, we can conclude that the management of post-burn hand deformities depends on several factors. Initial treatment of the burned hand is of great importance for the prevention of secondary deformities. In secondary burn management the first step is the release of the contracture, which should be complete and include all contracted structures. The second step is the proper selection of methods of coverage for resultant defects, using either skin grafts or flaps depending on the presence of exposed tendons, nerves, or joints. The third step in order to obtain a very good function is the activation of an intensive physiotherapy programme immediately after the operation.

Objectives: Photodynamic therapy (PDT) and inhibition of cathepsin B proteases by cystatin (cysteine proteinase inhibitor, CPI) are potential new tumour treatment modalities. We have investigated the efficacy of PDT and CPI alone and in combination on a solid mammary carcinoma transplanted into Wistar rats., Materials and Methods: Intraperitoneally injected single doses of chlorine e6 or HpD as photosensitizers were excited at 630 nm (90 J/cm(2)). CPI (500 micro g per animal) was injected around the tumour daily during the 8-day treatment. Inoculation of tumour was either on day 1 of the protocol, or 8 days before. On day 8, tumour size was measured, tumour necrosis and vascularization were determined based on haematoxylin and eosin (H&E)-stained sections and serum vascular endothelial growth factor (VEGF) levels measured using an enzyme-linked immunosorbent assay kit., Results: No differences (two-way anova) were found for treatments started with various time lags. At doses where CPI or PDT alone had no or negligible effect, their combination caused a marked (P < 0.001) decrease in serum VEGF, paralleled by a significant decrease in tumour size and number of capillary vessels, and a significant increase in necrosis (up to 80% of the tumour tissue)., Conclusions: The combination of PDT and CPI could be a useful approach in tumour therapy as the two agents appear to be synergistic and probably decrease VEGF production by the tumour tissue.

Purpose: Serum cathepsin B (CB), Total Sialic acid (TSA), total sialic acid (TSA) and lipid bound sialic acid (TSA) concentrations more useful than the other markers investigated for detecting different malignancies. Our aim was to investigate the possible correlation between serum CB with TSA, LSA in colorectal carcinoma with pathological stages progressed of the disease., Methods: The study was performed on 177 patients (109 patients with colon and 68 patients with rectal) and 50 healthy individuals comprised the control group. Serum CB activity was determined using fluorogenic substrate. Serum TSA and LSA Concentrations were measured according to the method described by Katopodis., Results: Plasma CB and TSA levels in the tumor group were significantly increased in comparison with the controls group (P < or = 0.0001). No significant differences were observed in LSA level between the tumor group and the controls group. T/N ratios for CB, TSA elevated 2.3-fold, 2.5-fold respectively). LSA 1.8-fold. Serum CB activity, TSA concentrations values in plasma samples of patients were increased significantly with pathological stages progressed (P < or = 0.0001). CB is seen to correlate more strongly with TSA in tumor group (P < or = 0.0001, r= 0.7277) in comparison with controls group. These correlations became more significant as the stage of the disease progressed., Conclusion: The present investigations indicate that CB activity, serum TSA, concentrations are sensitive markers for detecting and earliest diagnosis of colorectal cancer. These markers with other clinical and biochemical criteria may play important metabolic roles in cancer progression.

Aim: Cysteine peptidase (CP) and its inhibitor (CPI) are a matrix protease that may be associated with colorectal carcinoma invasion and progression, and vitamin E is also a stimulator of the immunological system. Our purpose was to determine the correlation between the expression of cysteine peptidases and their endogenous inhibitors, and the level of vitamin E in sera of patients with colorectal cancer in comparison with healthy individuals., Methods: The levels of cysteine peptidases and their inhibitors were determined in the sera of patients with primary and metastatic colorectal carcinoma and healthy individuals using fluorogenic substrate, and the level of vitamin E was determined by HPLC., Results: The levels of cysteine peptidases and their inhibitors were significantly higher in the metastatic colorectal cancer patients than that in the healthy controls (P<0.05). The activity of CP increased 2.2-fold, CPI 2.8-fold and vitamin E decreased 3.4-fold in sera of patients with metastasis in comparison with controls. The level of vitamin E in healthy individuals was higher, whereas the activity of cysteine peptidases and their inhibitors associated with complexes was lower than that in patients with cancer of the digestive tract., Conclusion: These results suggest that the serum levels of CP and their inhibitors could be an indicator of the prognosis for patients with metastatic colorectal cancer. Vitamin E can be administered prophylactically to prevent digestive tract neoplasmas.

Aim: To examine the effectiveness of human placental inhibitors, by injecting vitamin E to rats with transplanted Morris-5123 hepatoma, on the expression of cathepsins B and L in tumor, liver, lung and blood sera after transplantation of Morris 5123 hepatoma., Methods: Animals were divided into 10 groups receiving three different concentrations of vitamin E and inhibitors along or in combination and compared with negative control (healthy rats) and positive control (tumor rats). Effectiveness of treatment was evaluated with regard to survival time, tumor response and determination of the activities of proteolytic enzymes and their inhibitors using flurogenic substrates., Results: Cathepsins B and L activities were elevated by 16-fold in comparison with negative control tissues, and their endogenous inhibitor activity decreased by 1.2-fold before treatment. In several cases, tumors completely disappeared following vitamin E plus human placental cyteine protease inhibitor (CPI) compared with controls. The number of complete tumor responses was higher when 20 m/kg vitamin E plus 400 microg of CPI was used, i.e. 7/10 rats survived more than two mo. Cathepsins B and L were expressed significantly in tumor, liver, lung tissues and sera in parallel to the increasing of the endogenous inhibitor activity compared with the controls after treatment (P<0.0001)., Conclusion: The data indicate formation of metastasis significantly reduced in treated rats, which might provide a therapeutic basis for anti-cancer therapy.

Objective: Cathepsin D (CD) is one of the main proteolytic enzymes contributing to the development of cancer. The aim of this study was to CD activity assay in the homogenates of tissues from the centre of the tumour (0) and tumour free area 2 cm, and 5 cm from the tumour border in human colorectal cancer. Activity in the centre of the tumour was compared with immunohistochemical expression CD., Methods: CD activity was measured using acid denatured Hb as a substrate. For immunohistochemical staining peroxidase method was used., Results: Activity of CD was significantly higher (15-fold) in tumour tissue homogenates in comparison to normal mucosa adjacent (control) (p < or = 0.0001) and raised parallel to the stage of tumour tissue differentiation grade. CD activity decreased significantly (p < or = 0.0001) with the distance from the tumour border 2 cm (12.7 fold) and 5 cm (5.7 fold) in comparison to the centre of the tumour. In immunohistochemical examinations CD was detected as diffuse cytoplasmic as well as fine granular staining of the cytoplasm, with occasional coarse cytoplasmic granules staining in the same cases that were positive for both. Positive staining was observed in 2 of 3 in well-differentiated (66%), 4 of 10 in moderately-differentiated (40%) and 4 of 5 in poorly-differentiated (80%), tubular adencarcinomas represented: 3 of 7 (42%) and 9 of 13 in invasive adencarcinoma (69%)., Conclusion: We have observed a wide range of cathepsin D and their antigen expressions patterns in colorectal tumours with the development the disease stage, this finding may be used as a daignostic tumor marker in colorectal cancer.

Aim: Actin microfilaments are components of cytoskeleton, the structure involved in many cellular functions, including cell motility, and morphology, its necessary for tumor progression and metastasis. We investigated the effects of vitamin E and human placetal cysteine protease inhibitor (CPI) on actin content and polymerization after implantation the hepatoma Morris 5123 tumor in Buffalo rat., Methods: We measured the size and survival animals treated with human placental cysteine protease inhibitor (CPI) plus vitamin E and none treated rats. Also measured the actin content and polymerization in the tumor and liver tissues by the inhibition of DNase I from bovine pancreas under standard assay conditions, Results: We observed that the combination 10 mg of vitamin E plus 200 microg CPI obtained the best results than authors. In those cases the animals survived for longer than 4 weeks. In numerous cases the 70 % of tumors disappeared following CPI and vitamin E application. The number of complete tumor responses was higher after combination 10 mg of vitamin E plus CPI 200 microg i.e. 5/7 rats than others group. We showed statistically significant decrease of monomeric (G), filamentous (F) and total actin as well as the F:G ratio level in tumor tissues after the rats was treated with CPI plus vitamin E in comparison with control animals., Conclusions: The new therapy may be the way for therapeutic intervention, aimed at stopping and possibly reversing the process of metastatic growth, with the use of drugs affecting actin polymerization.

We studied the relation between the antipapain activity of cysteine proteinase inhibitors (CPI) and immunohistochemical staining for cystatin C, using anti-chicken cystatin antibodies, in the colorectal cancer tissues. In primary tumour tissues immuno-peroxidase reactivity was present in the cytoplasm and on the cell surface membranes. Sections of non malignant tissues showed no staining. The percentages of positive staining were greater for adenocarcinoma than carcinoma,100% and 77% respectively. Antipapain activity which was increased in malignant tissues in comparison to control, rose successively from well differentiated carcinomas through moderately to poor differentiated. Invasive adenocarcinomas had higher antipapain activity than noninvasive ones. The results indicated that immunohistochemical detection of cystatin using anti-chicken cystatin antibodies could be useful in studying the prognostic significance of cystatin C expression in colorectal cancer.

Enzymatic activity of cysteine peptidases (cathepsins B and L) --associated with carcinogenesis is controlled by their specific inhibitors. The study was objected to the effects enhanced by taxol and cisplatin in patients pretreated with the vitamin E, by determining the levels of cathepsins B and L in sera of patients with ovarian cancer. The activity of cysteine peptidase (CP) and their inhibitors (CPI) in serum from patients with ovarian cancer and noncancerous patients were measured by using fluorogenic substrate before and after the routine anticancer chemotherapy, and a complementary combination of chemotherapy with vitamin E. The cat B and L activities were significantly higher in patient sera with ovarian cancer than non-cancerous patients (0.0001 pounds sterling). The results shows that, inhibitory activity of CPI and complex form were significantly decreased from 4.6 mEU/mg protein in a group of non-cancerous patients to 0.7 mEU/mg protein in a group of patients with ovarian cancer (p < or = 0.0001). Supplementation with vitamin E after a cycle of therapy with toxic drugs caused a decrease of the cysteine peptidases activities, that is 2.8-fold in patients to whom 40 0mg of vitamin E per day was given in comparison with control, and 6-fold after the third course. The CPI and DCPI complex increased 3-fold and 2.3 fold respectively, as compared to a group of patients were vitamin E was not administered. We observed that vitamin E administered to the patients with ovarian cancer in periods between anticancer drugs therapy courses decreases the cysteine peptidases activity and increases the enzyme-inhibitor complexes level

5-aminolevulinic acid (5-ALA) is a precursor in synthesis of endogenous porphyrins used to sensitize tumor tissues in photodynamic therapy (PDT). It is administered topically into a tumor which after the certain time, required for porphyrins to accumulate, is irradiated with visible light from the proper source at established wavelength. Our main aim in the present study was to increase the penetration of 5-ALA through the skin and other tissues by addition of glycolic acid (GA) to 5-ALA on cell lines in vitro and on animals. We also applied 5-ALA ointment with glycolic acid to patients suffering from squamous cell carcinoma (SCC). In our study, we used 5-ALA, dimethyl sulfoxide (DMSO), ethylenediaminetetraacetic acid, disodium salt (EDTA) and GA together in one formulation (5-ALA-GA) on eucerin support. We compared both therapeutic and cosmetic effects in 5-ALA-GA-PDT and in control group of patients. Our results showed that modification of 5-ALA ointment by addition of 5% GA caused that the treated lesions responded with rapid regression. In 12 patients with single lesions of SCC type subjected to 5-ALA-GA-PDT, we observed 100% regression of tumors following single or repeated two-three times PDT. In vitro and in vivo in animals total porphyrin levels after addition of 5% GA increased significantly (P<0.01). These results provide evidence that addition of glycolic acid should be considered as the agent which enhances 5-ALA penetration in tissues and thus increases the effectiveness of photodynamic therapy.

Background: Many investigators have observed a correlation between the aggressiveness of malignant tumor growth and the levels of cysteine peptidases and their autogenous inhibitors. Cathepsins B and L are activated by pepsin in an acidic pH. This fact encouraged us to measure the activity of these enzymes in tissue samples of gastric cancer., Methods: We measured the activities of cathepsins B and L, and their precursors and inhibitors, in homogenates of tissue samples obtained from operations for gastric cancer. We compared the results for the homogenates of tissues from three different sites: the tumor center, the zone of cancer invasion (border of the tumor), and healthy tissue., Results: The highest activities of free cysteine peptidases and those in complexes with their inhibitors, as well as their precursors, were observed in the border of the tumor, while the activities in healthy tissue were significantly lower., Conclusion: The local activities of cysteine peptidases and their inhibitors reflect the topographical differences between the center of the tumor, the zone of invasion, and healthy tissues in gastric cancer patients. In addition, the results for the pattern of changes in the activity of cysteine peptidases according to the degree of tissue infiltration were not dependent on the method of measurement (colorimetry vs spectrofluorometry).

Background: Degradation of the basement membrane and surrounding extracellular matrix is likely to represent a key step in cancer invasion and metastasis. The purpose of this study was to determine whether gastric cancer tissues demonstrate higher cysteine proteases activities: cathepsins B and L during cancer progression in compression with non-cancerous tissues., Methods: We measured the expression of both cathepsins B and L in 30 patients with gastric cancer tissues and non-cancerous tissues activities by a fluorescence assay and immunohistochemical staining. We attempted to regulate cathepsin B and L expression using egg white cystatin., Results: The activities of cathepsins B and L were significantly higher in cancerous than in non-cancerous tissues (P

Mouse polyclonal antibodies against placental cysteine proteinase inhibitor (CPI) react with the placental 67 kDa CPI on Western blots, and CPI present in ovarian cancer homogenate and serum was shown by double immunodiffusion to react with the same antiserum. By immunohistochemical staining, positive expression of high molecular weight CPI was observed on the tumour cell surface in serous and endometrioid ovarian carcinomas with metastasis. Normal endometrioid tissue was not stained with anti-placental CPI antibodies. Cathepsin B and pro-cathepsin B median levels in ovarian cancer tissue homogenates increased progressively with FIGO stage of the disease. The enzyme level decreased 22-fold after treatment of tissue homogenates with 5 nM purified CPI. These results provide evidence that addition of CPI reduces the levels of cysteine-type cathepsins to those of normal non-cancerous values.

Cysteine cathepsin B and its endogenous inhibitor play an important role in tumor progression. Increase in cathepsin B expression and reduced levels of its inhibitors were associated with tumor malignancy in breast cancer. The objective of this study was to investigate the effects of a new therapy combining vitamin E and placental inhibitor on the level of endogenous protease inhibitor in sera and tumor tissues with mammary cancer. The inhibitor was used in doses of 100 and 200 micrograms per animal for 8 days. Vitamin E was added after the last treatment with inhibitor and was injected daily in doses of 10 and 20 mg per animal for one mouth. The size and survival time of treated animals as well as cathepsin B and the inhibitor activity in tumor and sera before and after treatment in comparison with the control groups were determined. The activity of cathepsin B significantly decreased both in tumor tissues and in sera (P < or = 0.0001). Cathepsin B activity in tumor tissue homogenates and in sera decreased two-fold and three-fold, respectively, after the animals were treated with vitamin E at a dose of 20 mg, and decreased five-fold and 15-fold, respectively, when treated with vitamin E plus inhibitor in comparison with untreated animals. Endogenous inhibitor activity increased six-fold and 12-fold in the sera and tissue homogenates, respectively, after the animals were treated with 200 micrograms of cysteine protease inhibitor plus 20 mg of vitamin E, in comparison with untreated animals. The total cure responses were higher in eight of 10 rats, as compared with untreated animals. The combination of placental inhibitor and vitamin E resulted in a significant reduction in breast metastasis and might provide a therapeutic basis for anti-metastasis therapy.

Many investigators studied the expression and activity of peptidases in critical steps of tumor progression, invasion and metastasis processes. Recent studies, however, indicate that cysteine peptidases are involved earlier in progression in tumor growth and metastatic sites. Extracellular peptidases probably co-operatively influence matrix degradation and tumor invasion through participation of "proteolytic cascades" in many carcinogenesis processes. In present review, we discuss the effect of interaction of cysteine peptidases from tumor cells and their role in physiological processes.

Cysteine peptidases and their endogenous inhibitors (CPI) have been shown to be involved in tumor progression and metastasis. Since their activity has been found to be changed in tumor tissue and/or body fluids of cancer patients, the determination of the peptidase/inhibitor levels is considered as a procedure of diagnostic value. Determination of cathepsin B, its precursor and inhibitor activity in homogenates of tumors and control breast tissue samples of patients with invasive ductal and lobular breast carcinoma and with benign breast disease (BBD) was performed using fluorometric assay. Immunohistochemical staining of the breast tissue samples was carried out using polyclonal antibody against cysteine peptidase inhibitor isolated from human placenta. Procathepsin B and cathepsin B were found to be significantly increased and their endogenous inhibitors decreased in homogenates of tumors from patients with breast cancer. A correlation between procathepsin B or cathepsin B activities as well as cysteine peptidase inhibitor activity and the histopathological grading of the tumor was observed. All samples of the tumor tissue showed positive immunostaining with antibody raised against cysteine peptidase inhibitor, while in the control tissue samples the immunostaining was much weaker. Significant difference observed between the activities of cathepsin B and/or its precursor in malignant and benign tumors might serve as a useful clinical indicator in discrimination between benign and invasive tumors.

Numerous studies have shown that lysosomal proteinases play an important role in carcinogenesis. The enzymatic activity of tumor-associated proteases is counter-balanced by specific inhibitors. Photodynamic therapy (PDT) is a technique which involves photoexcitation of sensitizing drugs retained in neoplastic tissue that is subsequently destroyed. Intraperitoneal injections of hematoporphyrin derivative (HpD) were given at a dose of 20 mg/kg in rats transplanted with mammary carcinoma. A halogen lamp was used 24 hours later at 630 +/- 20 nm and total dose--200 J/sq.cm. Cysteine proteinase inhibitor (CPI) was dissolved in saline and injected subcutaneously in doses of 50 mg and 200 mg per animal. The effectiveness of the treatment was evaluated with regard to survival time and tumor response and to depth of necrosis. In several cases tumors completely disappeared following HpD-PDT + CPI. The number of complete tumor responses was higher when PDT + 200 mg of CPI was used, i.e. 6 out of 10 rats. Promising results have also been obtained with regard to survival time of treated animals and to induction of tumor necrosis. We may presume that a combination of PDT and proteinase inhibitors could be a useful tool in further anticancer studies and, hopefully, in anticancer therapy.

Epileptic activity can modulate reactions of the autonomic nervous system. Although there is some evidence of a differential left/right hemispheric influence on the cardiovascular system, diverse investigations have shown controversial results. In our study, complex partial seizures of patients with temporal lobe epilepsy were recorded using subdural electrodes, thus providing reliable information on the focus side. We analyzed the preictal and ictal heart rates of 27 patients, 16 revealing right and 11 revealing left temporal foci. During the seizures, both groups showed a significant increase in heart rate. Preictal tachycardia was only significant in the right focus group, whereas no significant change in heart rates could be detected in the left focus group. Our results confirm a right hemispheric lateralization of sympathetic cardiac control.

Ten species of fungi representing the genera Alternaria, Aspergillus, Caldosporium, Curvularia, Fusarium, and Penicillium were examined for their relative resistance to gamma irradiation from a 137Cs source. Inactivation doses for dematiaceous fungi in agar medium ranged from 0.6 to greater than 1.7 megarads, whereas those for moniliaceous fungi were less than 0.3 megarad. D10 values (the dose required to reduce the inoculum by 1 log) for Curvularia geniculata (greater than 0.29 megarad) exceeded those for control spores of Bacillus pumilus (0.15 megarad).

A patient who survived rupture of a renal artery aneurysm in pregnancy is described. The aneurysm was caused by fibromuscular dysplasia of the renal artery.