Plasma metadherin mRNA expression in bladder cancer.

Urinary bladder cancer (BC) is the ninth most common cancer worldwide. At present, the clinical diagnosis of BC depends on self-reported symptoms, tissue biopsy specimens by cystoscopy and from voided urine cytology. However, cystoscopy is an invasive examination and voided urine cytology has low sensitivity, which might provoke misdiagnosis. The search for cancer biomarkers in blood is worthy of intense attention due to patients' comfort and ease of sampling. This work aimed to study expression of mRNA metadherin (MTDH) in plasma, serum BC specific antigen 1 (BLCA-1) and cystatin C as biomarkers of BC and their relation to different disease stages. This study included 59 BC patients, 11 patients with benign bladder lesion and 18 subjects as normal controls. MTDH expression was assessed by real time polymerase chain reaction, BLCA-1, and cystatin C by the enzyme linked immunosorbent assay. The three biomarkers were elevated in BC patients than patients with benign bladder diseases and controls. Patients with BC grade 3 and 4 had higher cystatin C, BLCA-1 and MTDH in comparison to patients with grade 1 and grade 2 (p=0.000). The receiver operating characteristic curve analysis showed that BLCA-1 at a cutoff point of 32.5 ng/ml and area under the curve of 1.00, had 100% accuracy, 100% sensitivity, 100% specificity, 100% positive predictive values and 100% negative predictive value. In conclusion, BLCA-1 was a better biomarker than cystatin C and MTDH. Cystatin C, BLCA-1 and MTDH levels, can differentiate between benign bladder lesion and BC and correlated with tumor grades.especially with OL-HDF compared to HF-HD, with acceptable albumin loss in the dialysate.

Nanoparticles integrating natural and synthetic polymers for in vivo insulin delivery.

The aims of the current study were to develop insulin-loaded nanoparticles comprised of various polymers at different compositions, and to evaluate their ability to lower blood glucose levels in diabetic rats following subcutaneous and oral administrations. Several combinations of natural and synthetic polymers have been utilized for preparation of nanoparticles including, chitosan, alginate, albumin and Pluronic. Nanosized (170 nm-800 nm) spherical particles of high encapsulation efficiency (15-52%) have been prepared. Composition and ratios between the integrated polymers played a pivotal role in determining size, zeta potential, and in vivo hypoglycemic activity of particles. After subcutaneous and oral administration in diabetic rats, some of the insulin-loaded nanoparticles were able to induce much higher hypoglycemic effect as compared to the unloaded free insulin. For instance, subcutaneous injection of nanoparticles comprised of chitosan combined with sodium tripolyphosphate, Pluronic or alginate/calcium chloride, resulted in comparable hypoglycemic effects to free insulin, at two-fold lower dose. Nanoparticles were well-tolerated after oral administration in rats, as evidenced by by measuring levels of alanine aminotransferase, aspartate aminotransferases, albumin, creatinine and urea. This study indicates that characteristics and delivery efficiency of nanomaterials can be controlled via utilizing several natural/synthetic polymers and by fine-tuning of combination ratio between polymers.

Sexual functions in women with focal epilepsy: Relationship to demographic, clinical, hormonal and psychological variables.

OBJECTIVES: Sexual dysfunctions [SDs] are common in women with epilepsy [WWE] but related studies were neglected in our locality. We aimed to determine the frequencies and severities of SDs and their clinical, hormonal and psychological determinants in WWE. PATIENTS AND METHODS: This study included 120 adults [mean age: 36.35 ± 2.89yrs] with temporal [63.33 %] and frontal [36.67 %] lobe epilepsies and treated with carbamazepine [CBZ] [n = 60] or oxcarbazepine [OXC] [n = 60] for mean duration of 18.63 ± 4.33yrs. Patients were assessed using Female Sexual Function Index [FSFI] questionnaire, Beck Depression Inventory [BDI-II] and Hamilton Anxiety Rating Scale [HAM-A]. Total testosterone, sex hormone binding globulin [SHBG] and free androgen index [FAI] were measured to assess endocrinal status. PATIENTS AND METHODS: This study included 120 adults [mean age: 36.35 ± 2.89yrs] with temporal [63.33 %] and frontal [36.67 %] lobe epilepsies and treated with carbamazepine [CBZ] [n = 60] or oxcarbazepine [OXC] [n = 60] for mean duration of 18.63 ± 4.33yrs. Patients were assessed using Female Sexual Function Index [FSFI] questionnaire, Beck Depression Inventory [BDI-II] and Hamilton Anxiety Rating Scale [HAM-A]. Total testosterone, sex hormone binding globulin [SHBG] and free androgen index [FAI] were measured to assess endocrinal status. RESULTS: The majority had occasional/rare frequency of seizures [76.67 %] and well controlled on antiepileptic drugs [AEDs] [81.67 %]. Compared to healthy women, WWE had lower total testosterone and FAI and higher SHBG levels. Compared to women on CBZ, those on OXC had lower frequency and well controlled seizures on medication [P = 0.0001 for both], higher testosterone [P = 0.01] and FAI [P = 0.001] and lower SHBG [P = 0.001] levels. Compared to controls, WWE had significantly higher frequencies and severities of SDs [total sexual function, desire, arousal, lubrication, orgasm, satisfaction and pain] and depression and anxiety symptoms. OXC therapy was associated with lower SDs [FSFI: P = 0.033] and anxiety symptoms [P = 0.025] compared to CBZ therapy. In multiple logistic regression analyses, determinants of SDs were the higher seizures frequency, increasing severities of depression and anxiety but not lower androgen levels or type of epilepsy or AEDs. CONCLUSIONS: Different aspects of SD and depression and anxiety symptoms were frequent in WWE. Determinants of SDs were the higher frequency of seizures and increasing severities of depression and anxiety. OXC had better control on seizures and thus lower frequencies and severities of SDs and depression and anxiety symptoms. Thus optimizing seizure control is important for psychological state and healthy sexual function in WWE.

Development and in vivo evaluation of chitosan nanoparticles for the oral delivery of albumin.

Albumin is used as a plasma expander in critically ill patients and for several other clinical applications mainly via intravenous infusion. Oral administration of albumin can improve patient compliance although limited oral bioavailability of proteins is still a major challenge. Although nanomaterials have been extensively utilized for improving oral delivery of proteins, albumin has been utilized only as either a model drug or as a carrier for drug delivery. In the current study, for the first time, chitosan nanoparticles have been developed and extensively optimized to improve oral bioavailability of albumin as a therapeutic protein. Several characterizations have been performed for the albumin-loaded nanoparticles (e.g. drug encapsulation efficiency, DSC, FTIR, particle size, zeta potential, morphology, release kinetics, and enzymatic stability). Nanosized spherical particles were prepared and demonstrated high stability over three months either in a powdered form or as suspensions. Sustained release of albumin over time and high enzymatic stability as compared to the free albumin were observed. In vivo, higher serum concentrations of albumin in normal rabbits and cirrhotic rats were attained following oral and intraperitoneal administrations of the albumin-loaded nanoparticles as compared to the free albumin. The nanoparticles developed in the current study might provide efficient nanovehicles for oral administration of therapeutic albumin.

Iron deficiency and cyanotic breath-holding spells: The effectiveness of iron therapy.

Aim: Frequent cyanotic breath holding spells cause fear and severe anxiety to parents. This study aimed to evaluate clinical, laboratory and treatment characteristics of children with cyanotic breath holding spells. Methods: Included were 180 children (mean age: 1.82 ± 0.53 years) with cyanotic breath holding spells. They were divided into three groups: with iron deficiency, with iron deficiency anemia and without iron deficiency. Blood hemoglobin (HB), ferritin and iron concentrations were measured at baseline and after 3 and 6 months of iron treatment. Results: The mean spell frequency was 24.57 ± 7.31/months, 83% had spells after the age of 1 year, 37% had daily spells, 16% had family history of spells, and 61% had Iron deficiency/Iron deficiency anemia (p = .001). No significant difference in the frequency of spells between children with iron deficiency and those with Iron deficiency anemia. Compared to patients without iron deficiency, there was significant reduction of spells frequency, increased hemoglobin, ferritin and iron levels after 3 and 6 months of iron therapy (p = .0001). Negative correlations were observed between spell frequency with hemoglobin (p = .001), ferritin (p = .0001) and iron (p = .001) levels. Conclusion: Not only Iron deficiency anemia but also iron deficiency alone without anemia is associated with a risk of high-frequency cyanotic breath holding spells. Iron therapy results in reduction in spells' frequency which was correlated with increasing ferritin and iron levels.

Non-neoplastic Portal Vein Thrombosis in HCV Cirrhosis Patients: Is it an Immuno-Inflammatory Disorder?

BACKGROUND AND AIMS: Portal vein thrombosis (PVT) is a critical complication in cirrhotic patients. We explored the role of the activated factor VII-antithrombin (FVIIa-AT) complex and enhanced monocytic tissue factor (TF) expression in the development and prediction of non-neoplastic PVT in cirrhotic patients. MATERIAL AND METHODS: A total of 30 HCV-cirrhosis patients were included in our study. They were compared to 35 cirrhotic patients without PVT, 15 non-cirrhotic patients with PVT, and 15 healthy controls. The plasma level of the FVIIa-AT complexes was analyzed by ELISA. MIF CD142, CD86, and HLA-DR on monocytes (CD14) were determined by flow cytometry. RESULTS: Compared with cirrhotic patients without PVT, cirrhotic patients with PVT had comparable plasma values of FVIIa, AT, and the FVIIa-AT complex. However, they had significantly lower values compared to non-cirrhotic patients with PVT and healthy controls. Cirrhotic patients with PVT had increased monocytic TF expression (MIF CD142) compared to non-PVT cirrhotic patients and healthy controls [86.5 (93.5) vs. 18 (32.0) and 11.0 (6.0), respectively; p < 0.001 for each]. However, cirrhosis PVT could not be distinguished from non-cirrhosis PVT. The area under the ROC curve of MIF CD142 was 0.759 (0.641- 0.876; p = 0.000) at an optimal cut-off value of 45, which yielded a sensitivity of 60% and a specificity of 77.1%, as well as a PPV and NPV of 69.2% for each. CONCLUSION: Enhanced expression of monocytic TF may have a role in the development and prediction of non-neoplastic PVT in HCV-cirrhosis patients. Large multicenter studies are necessary to validate our results.

Intestinal barrier integrity and function in infants with cholestasis.

BACKGROUND/AIMS: The safety of the human body is maintained by effective monitoring of the mucosal surface integrity and protection against potentially harmful compounds. This function of the gut called intestinal barrier function can be affected by cholestasis and the absence of bile in the intestinal lumen. We aimed to determine whether the gut barrier integrity is impaired in infants with cholestasis by evaluation of the intestinal fatty acid binding proteins (I-FABP) and ileal bile acid binding protein (I-BABP) as markers of intestinal epithelial cell damage and plasma D-lactate level as a marker of gut wall permeability. METHODS: This case-control study included 53 infants with cholestasis and 29 controls. Serum levels of I-FABP, I-BABP, and D-lactate were measured in all subjects. RESULTS: Both groups of patients with neonatal hepatitis and biliary atresia showed significantly higher levels of I-FABP and I-BABP than the controls. There were no differences in the serum D-lactate level between the cases and controls. There was no difference between the two groups of patients (I and II) regarding any of the parameters studied. No significant correlations between serum levels of I-FABP, I-BABP, or D-lactate and total or direct bilirubin levels were found in the cholestatic infants. CONCLUSIONS: The intestinal epithelial barrier integrity is breached nearly in all parts of the intestine in infants with cholestasis. Further research is recommended to determine the impact of this finding on the management of these infants. The relationship between physical intestinal barrier damage and its functional failure remains subject for further research.

Impact of Thrombophilia on the Risk of Hypoxic-Ischemic Encephalopathy in Term Neonates.

BACKGROUND: The incidence of neonatal hypoxic-ischemic encephalopathy (HIE) is reportedly high in countries with limited resources. Its pathogenesis is multifactorial. A role for thrombophilia has been described in different patterns of preterm and full-term perinatal brain injury. AIM: This study aims to identify risk factors associated with neonatal HIE and also to determine the contributions of genetic thrombophilia in the development of neonatal HIE. METHODS: Sixty-seven neonates with HIE and 67 controls were enrolled in the study. Clinical history and examination were undertaken. Patients and controls were tested for the presence of factor V G1691A and prothrombin G20210A mutations. In addition, protein S, protein C, and antithrombin III levels were assessed. RESULTS: Parental consanguinity and performing emergency cesarean section (CS) were significant risk factors for neonatal HIE (odds ratio [OR] 6.5, 95% confidence interval [CI] 2.6-15.3, P < .001, OR 12.6, 95% CI 2.52-63.3, P = .002, respectively). No significant difference was found regarding maternal age and parity. About 33% of cases and 6% of controls were found to have at least 1 thrombophilic factor ( P < .001). Factor V G1691A mutation significantly increased the risk of neonatal HIE (OR 4.5, 95% CI 1.4-14.5, P = .012), while prothrombin G 20210A mutation and protein C deficiency were not. CONCLUSION: Parental consanguinity, emergency CS, and factor V mutation may contribute to the higher risk of developing neonatal HIE.

Adiponectin, leptin and insulin levels at birth and in early postnatal life in neonates with hypoxic ischemic encephalopathy.

BACKGROUND: Hypoxic ischemic encephalopathy (HIE) occurs in one to three per 1000 live full-term births. Fifteen to twenty percent will die in the postnatal period, and an additional 25 % will develop severe and permanent neuropsychological sequalae. The control of growth and nutritional status in the fetus and neonate is a complex mechanism, in which also hormones produced by adipose tissue, such as adiponectin and leptin are involved. The aim of this study was to measure the levels of adiponectin, leptin and insulin in neonates with HIE at birth and in early postnatal life and comparing them with normal healthy AGA and SGA neonates. METHODS: This study carried out on 80 full-term neonates born in Minia university hospital during the period from May 2013 to December 2014. They were divided into group I included 25 neonates with HIE and group II included 55 normal healthy neonates (30 appropriate for gestational age (AGA) and 25 small for gestational age (SGA)). Weight, length, head circumference, body mass index (BMI), glucose, adiponectin, leptin and insulin levels were measured for all neonates. Adiponectin, leptin and insulin levels were compared between neonates with HIE and normal healthy neonates as well as between AGA and SGA neonates at birth, 2nd and 6th days of life. RESULTS: Adiponectin and leptin levels were significantly higher at birth then began to decrease during the first postnatal week in all neonates while insulin level increased during the same period. Serum adiponectin levels were significantly lower while serum leptin and insulin levels were significantly higher in neonates with HIE than healthy neonates. In all neonates, the serum adiponectin level was positively correlated at birth with weight, length, BMI and leptin levels but not with insulin level. In neonates with HIE, serum adiponectin level was not correlated with weight, BMI, leptin level or insulin level. In all neonates, the serum leptin level was positively correlated at birth with body weight, height and BMI. In neonates with HIE serum leptin levels were not correlated with weight, BMI or insulin level after birth. There were no correlations between either leptin or adiponectin serum levels or any of the studied parameters in neonates with HIE. CONCLUSIONS: Neonates who are suffering from HIE had lower serum levels of adiponectin and higher serum levels of leptin and insulin than normal healthy neonates at birth and during the early postnatal period. The decline of leptin and increased the insulin levels after birth in all neonates may be important for the stimulation of feeding behavior and the acquisition of energy homeostasis during the early postnatal life. Positive significant correlations between adiponectin, leptin, body weight and body mass indices were present in normal healthy neonates but not in neonates with HIE reflecting the effect of hypoxia on the regulatory mechanisms controlling the adipose tissue functions.

Seminal fluid analysis and testicular volume in adults with epilepsy receiving valproate.

Epilepsy and its medications adversely affect reproductive and sexual functions and fertility. This study aimed to assess sperm parameters and testicular volume in men with epilepsy on valproate (VPA). Included were 55 patients with idiopathic epilepsy with a mean age of 31.86 ± standard deviation (SD) 6.55 years, mean illness duration of 12.50 ± SD 5.10 years, and a mean treatment time of 9.55 ± SD 0.85 years. Sex hormone profile, semen analysis, testicular volume and total seminal plasma carnitine were determined. Compared to controls, patients had lower levels of free testosterone (p<0.01), sperm concentration (p<0.0001) and count (p<0.0001), carnitine (p<0.01), and testicular volume (p<0.01), and higher rates of immotile sperm (p<0.001) and abnormal forms (p<0.0001). Significant correlations were identified between sperm count, motility, immotile sperm, abnormal forms, testicular volume, carnitine levels and duration of illness, duration of treatment with VPA and VPA dose. Multivariable analysis demonstrated that duration of treatment with VPA, sperm count, motility and abnormal forms were significantly associated with seminal plasma carnitine. Long-term VPA treatment is adversely associated with reduced sperm count and motility, increased abnormal sperm count and reduced testicular volume. This may contribute to reduced fertility.

Diabetes worsening of hepatitis C cirrhosis: are alterations in monocytic tissue factor (CD 142) is the cause?

BACKGROUND & AIM. The mechanisms by which type 2 diabetes mellitus (T2DM) worsen liver function are not yet established. Tissue factor (TF) is a protein that participates in hemostatic, immune and inflammatory processes. To test the hypothesis that T2DM contributes to clinical outcome through changes of TF expression on monocytes and to investigate the association between antidiabetic therapies and monocytic TF expression in HCV-related cirrhotic patients with T2DM. MATERIAL AND METHODS. In HCV-related cirrhotic patients (139 diabetics and 130 non diabetics) compared with 100 matched diabetic patients and 100 Controls; the flowcytometric analysis of CD14, TF (CD142), costimulatory molecules; CD86 and HLA-DR on monocytes were determined. RESULTS. Cirrhotic patients with T2DM have increase in the expression of monocytic TF and CD86 in comparison with cirrhotic non-diabetic, diabetic and healthy control; which increase significantly with increase of the stage of the Child-Pugh score. The expression of HLA-DR is significantly lower in cirrhotic patients than controls. Albeit, there were no significant differences in the HbA1c levels between the three groups, the use of exogenous insulin were associated with significantly higher monocytic TF expression than those in sulphonylurea and insulin sensitizer group (P < 0.03 for both). CONCLUSIONS. The monocytic TF as a significant link connecting inflammatory and immunological phenomena can partially explain a lot of events in HCV- related cirrhotic patients with T2DM. The use of exogenous insulin was associated with significantly higher TF expression than sulphonylurea and insulin sensitizer. Future target therapy against TF may be beneficial for T2DM cirrhotic patients.

Novel technique for biliary reconstruction using an isolated gastric tube with a vascularized pedicle: a live animal experimental study and the first clinical case.

BACKGROUND: Biliary tract reconstruction continues to be a challenging surgical problem. Multiple experimental attempts have been reported to reconstruct biliary defects with different materials and variable outcome. Our aim was to evaluate a new method for biliary reconstruction using an isolated pedicled gastric tube in a live animal trial and also to present the first clinical case. METHODS: Seven mongrel dogs underwent biliary reconstruction using gastric tube harvested, completely separated from the greater curvature, and based on a vascularized pedicle with the right gastroepiploic vessels. The tube was interposed between the common bile duct (CBD) and the duodenum. Postoperative mortality, morbidity, liver functions, gross and microscopic histological picture were assessed. The first clinical case was also presented where, in a patient with post-cholecystectomy biliary injury, an isolated pedicled gastric tube was interposed between the proximal and distal ends of the CBD. RESULTS: One dog did not recover from anesthesia and another one died postoperatively from septic peritonitis. Five dogs survived the procedure and showed uneventful course and no cholestasis. The mean anastomotic circumference was 4.8 mm (range 4-6) for CBD anastomosis and 6.2 mm (range 5-7) for duodenal anastomosis. Histologically, anastomotic sites showed good evidence of healing. In the first clinical case, the patient showed clinical and biochemical improvement. Endoscopic retrograde cholangiography was feasible and assured patent biliary anastomoses. CONCLUSION: In mongrel dogs, biliary reconstruction using pedicled gastric tube interposition between CBD and duodenum is feasible with satisfactory clinical results, anastomotic circumference and histological evidence of healing. The technique is also feasible in human and seems to be promising.

Laparoscopic versus open cholecystectomy in patients with liver cirrhosis: a prospective, randomized study.

BACKGROUND: Gallstones are more common in patients with liver cirrhosis than in healthy individuals. Higher morbidity and mortality were reported in cirrhotic patients with either laparoscopic or open cholecystectomy. The aim of this study was to compare laparoscopic and open cholecystectomy in cirrhotic patients with symptomatic cholelithiasis in a prospective, randomized manner. MATERIALS AND METHODS: Thirty patients with symptomatic cholelithiasis associated with Child-Pugh class A or B liver cirrhosis were prospectively and randomly grouped equally to either laparoscopic or open cholecystectomy. The two groups were compared regarding operative time, morbidity, mortality, postoperative liver function, and hospital stay. RESULTS: The two groups were comparable regarding demographic data, preoperative and postoperative Child-Pugh scoring, mean operative time (57.3 minutes for laparoscopic and 48.5 for open), and complications (33.3% for each). Hospital stay was shorter for the laparoscopic group. One conversion (6.7%) to open surgery was reported. No periopertive mortality occurred in either group. CONCLUSIONS: For Child-Pugh class A and B cirrhotics, laparoscopic cholecystectomy is comparable to the open approach regarding operative time, morbidity, mortality, and effect on liver function, but with shorter hospital stay. Considering the other well-documented advantages of the laparoscopic approach, namely, less pain, earlier mobilization and feeding, and better cosmoses, laparoscopic cholecystectomy would be the first choice in cirrhotic patients.