Radiological evaluation of postoperative complications after non-sleeve gastrectomy bariatric procedures

Background: Obesity is a medical condition, which may lead to serious related diseases, ultimately, resulting in many morbidities and early mortality. Its management involves many approaches of which bariatric surgery is considered nowadays as one of the most effective treatment for it. However, follow up of postoperative complications of this surgery by effective radiological method as computed tomography (CT) is important for assessment of its success.Objective: The aim of this study was to illuminate the radiological signs and features of postoperative complications after non sleeve bariatric procedures and stressing the importance of using multi-slice CT (MSCT), and fluoroscopic study for detection of these complications. Patients and methods: An observational cohort study for 275 patients with suspected complications after non sleeve gastrectomy bariatric procedures, including 195 patients after Roux-en-Y gastric bypass (RYGB), 76 patients after laparoscopic adjustable gastric banding (LAGB) and 4 patients after intragastric balloon placement was done. These patients were subjected to either multi-slice CT and or fluoroscopy. Results: We detected complications in 21 patients out of the 195 patients who underwent RYGB: leakage, abscess, intestinal obstruction, internal hernia, port site ventral hernia, intussusception, fistula between the gastric pouch and the excluded stomach and hiatus hernia. On the other hand, 8 out of 76 patients operated by LAGB developed complications: band slippage, band erosion, pouch dilatation and tubal disconnection. Lastly two out of the 4 patients who placed intra-gastric balloon encountered other complications: gastric outlet obstruction, spontaneous balloon deflation and distal migration with intestinal obstruction.Conclusion: It could be concluded that bariatric procedures may be followed by many complications and accurate diagnosis of these problems by proper radiological procedures as MSCT is imperative

Molecular hybridization design and synthesis of novel spirooxindole-based MDM2 inhibitors endowed with BCL2 signaling attenuation:A step towards the next generation p53 activators

Despite the achieved progress in developing efficient MDM2-p53 protein-protein interaction inhibitors (MDM2 inhibitors), the acquired resistance of tumor cells to such p53 activators posed an argument about the druggability of the pathway. Combination studies disclosed that concomitant inhibition of MDM2 and BCL2 functions can sensitize the tumor cells and synergistically induce apoptosis. Herein, we employed a rapid combinatorial approach to generate a novel series of hybrid spirooxindole-based MDM2 inhibitors (5a-s) endowed with BCL2 signaling attenuation. The adducts were designed to mimic the thematic features of the chemically stable potent spiro[3H-indole-3,2′-pyrrolidin]-2(1H)-ones MDM2 inhibitors while installing a pyrrole ring on the core via a carbonyl spacer inspired by the natural product marinopyrrole A that efficiently inhibits BCL2 family functions by various mechanisms. NCI 60 cell-line panel screening revealed their promising broad-spectrum antiproliferative activities. The NCI-selected derivatives were screened for cytotoxic activities against normal fibroblasts, MDA-MB 231, HepG-2, and Caco-2 cells via MTT assay, subjected to mechanistic apoptosis studies for assessment of p53, BCL2, p21, and caspase 3/7 status, then evaluated for potential MDM2 inhibition utilizing MST assay. The most balanced potent and safe derivatives; 5i and 5q were more active than 5-fluorouracil, exhibited low μM range MDM2 binding (KD =1.32 and 1.72 μM, respectively), induced apoptosis-dependent anticancer activities up to 50%, activated p53 by 47-63%, downregulated the BCL2 gene to 59.8%, and reduced its protein level (13.75%) in the treated cancer cells. Further downstream p53 signaling studies revealed > 2 folds p21 upregulation and > 3 folds caspase 3/7 activation. Docking simulations displayed that the active MDM2 inhibitors resided well into the p53 binding sites of MDM2, and shared key interactions with the co-crystalized inhibitor posed by the indolinone scaffold (5i, 5p, and 5q), the halogen substituents (5r), or the installed spiro ring (5s). Finally, in silico ADMET profiling predicted acceptable drug-like properties with full accordance to Lipinski's, Veber's, and Muegge's bioavailability parameters for 5i and a single violation for 5q

Synthesis of Some Novel Urea, Thiourea and Amide Derivatives through Three Components one pot Reaction and their Anti-tumor Activity

The one-pot three component condensation of catechol and resorcinol with aromatic aldehydes and amides, thioamides such as urea, thiourea, thiosemicarbazide and acetamide under solvent free and neutral conditions to afford urea, thiourea and amide derivatives in high yields. The antitumor activity of some of the synthesized products was tested. Keywords: Three component condensation; 4H-benzo[e]-[1,3]oxazin-7-ol; Dioxoindenylurea; Antitumor activity

A Convenient Synthesis of Some Diarylurea and Thiourea Derivatives as Antimicrobial Compounds

A simple and efficient method has been developed for the synthesis of unsymmetrical 1,3-diarylurea and thiourea derivatives (3 and 4)  from phenylisocyanate or phenylisothiocyanate with  various aromatic amines. Unsymmetrical bis-diarylthiourea derivative (8b) reacted with diethyl malonate, ethyl chloroacetate and phenyl hydrazine, while (12) reacted with hydrazine hydrate, hydroxylamine hydrochloride, ethyl cyanoacetate and malononitrile. All compounds are characterized by I.R, 1H-NMR, 13C-NMR and MS spectral data. A comparison of synthesis of the products by conventional method and by microwave has also been undertaken. The screened antibacterial activity of the products has been recognized. Keywords: Phenylurea, Phenylthiourea, Thiazolidine, Microwave, One pot reaction, Antimicrobial activit

CXCL16 and oxLDL are induced in the onset of diabetic nephropathy

Diabetic nephropathy (DN) is a major cause of end-stage renal failure worldwide. Oxidative stress has been reported to be a major culprit of the disease and increased oxidized low density lipoprotein (oxLDL) immune complexes were found in patients with DN. In this study we present evidence, that CXCL16 is the main receptor in human podocytes mediating the uptake of oxLDL. In contrast, in primary tubular cells CD36 was mainly involved in the uptake of oxLDL. We further demonstrate that oxLDL down-regulated α3-integrin expression and increased the production of fibronectin in human podocytes. In addition, oxLDL uptake induced the production of reactive oxygen species (ROS) in human podocytes. Inhibition of oxLDL uptake by CXCL16 blocking antibodies abrogated the fibronectin and ROS production and restored α3 integrin expression in human podocytes. Furthermore we present evidence that hyperglycaemic conditions increased CXCL16 and reduced ADAM10 expression in podocytes. Importantly, in streptozotocin-induced diabetic mice an early induction of CXCL16 was accompanied by higher levels of oxLDL. Finally immunofluorescence analysis in biopsies of patients with DN revealed increased glomerular CXCL16 expression, which was paralleled by high levels of oxLDL. In summary, regulation of CXCL16, ADAM10 and oxLDL expression may be an early event in the onset of DN and therefore all three proteins may represent potential new targets for diagnosis and therapeutic intervention in DN

The way forward to public health in Gulf Cooperation Council (GCC) countries: a need for public health systems and law

Introduction: Public health systems in the Gulf Cooperation Council (GCC) Countries are not well established. The existing systems do not match with the current health challenges and with the use of innovative technology in healthcare (diagnosis, treatment or rehabilitation). This paper is intended to give an overview of the public health situation in these countries. It discusses the need for effective and integrated system of public health laws that plays important role in addressing high priorities in public health. Conclusion: The GCC countries have the infrastructure for estab¬lishing a national public health system. However it needs an effective integrated and organized mechanism to shape this system; based on acceptable guidelines and criteria in such a way that they are institutional and capable of meeting the population needs. This system should be cost- effective and investment in health sector should be looked upon as a sustained investment in human and societal development. Despite the great efforts exerted and achievements made, there are great challenges ahead that can be overcome by exhibiting a strong political will and having a united approach of all stakeholders

Design, Synthesis, Chemical and Biochemical Insights Into Novel Hybrid Spirooxindole-Based p53-MDM2 Inhibitors With Potential Bcl2 Signaling Attenuation

The tumor resistance to p53 activators posed a clinical challenge. Combination studies disclosed that concomitant administration of Bcl2 inhibitors can sensitize the tumor cells and induce apoptosis. In this study, we utilized a rapid synthetic route to synthesize two novel hybrid spirooxindole-based p53-MDM2 inhibitors endowed with Bcl2 signaling attenuation. The adducts mimic the thematic features of the chemically stable potent spiro [3H-indole-3,2′-pyrrolidin]-2(1H)-ones p53-MDM2 inhibitors, while installing a pyrrole ring via a carbonyl spacer inspired by the natural marine or synthetic products that efficiently inhibit Bcl2 family functions. A chemical insight into the two synthesized spirooxindoles including single crystal x-ray diffraction analysis unambiguously confirmed their structures. The synthesized spirooxindoles 2a and 2b were preliminarily tested for cytotoxic activities against normal cells, MDA-MB 231, HepG-2, and Caco-2 via MTT assay. 2b was superior to 5-fluorouracil. Mechanistically, 2b induced apoptosis-dependent anticancer effect (43%) higher than that of 5-fluorouracil (34.95%) in three studied cancer cell lines, activated p53 (47%), downregulated the Bcl2 gene (1.25-fold), and upregulated p21 (2-fold) in the treated cancer cells. Docking simulations declared the possible binding modes of the synthesized compounds within MDM2

The effect of serum angiotensin II and angiotensin II type 1 receptor gene polymorphism on pediatric lupus nephritis

Background: Angiotensin II (Ang II) is found to perpetuate inflammation and visceral damage in systemic lupus erythematosus (SLE). It mediates most of its actions through Ang II receptor type I (AT1) whose gene polymorphism A1166C (CC genotype) seems to have pathogenic effects. Objective: To measure serum Ang II and the frequency of AT1 receptor CC genotype among a group of Egyptian patients with pediatric onset lupus nephritis (pLN). Methods: This is a case-control cross sectional study which included 24 patients with pLN and 24 age and sex-matched healthy subjects as controls. Clinical evaluation and routine laboratory markers for SLE patients were done. SLE disease activity index (SLEDAI) and the British Isles Lupus Assessment Group (BILAG)-2004 renal score were measured. Serum Ang II was measured by enzyme linked immunosorbent assay and detection of ATI receptor CC genotype by polymerase chain reaction were done for both patients and controls. Results: Patients had significantly higher serum Ang II than the controls (p=0.0001). The frequency of AT1 receptor CC genotype was significantly higher among patients as compared to the control group (p=0.008). Both serum Ang II and AT1 receptor CC genotype were comparable between patients with proliferative LN class III and IV and those with LN class II (p>0.05). Serum Ang II did not correlate significantly with SLEDAI or BILAG-renal score (p>0.05). Conclusion: Serum Ang II and AT1 receptor CC genotype seem to have pathogenic role in pLN but with no deleterious effects on the phenotype of LN for further assessment.Keywords: Lupus nephritis; Angiotensin II; Angiotensin II type 1 receptor; Polymorphism; Pediatrics

Hepatitis B virus (HBV) genotypes in Egyptian pediatric cancer patients with acute and chronic active HBV infection

<p>Abstract</p> <p>Background</p> <p>There are eight genotypes of hepatitis B virus (A-H) and subgenotypes are recognized. Genotyping can be accomplished based on a partial sequence of HBV genome such as the pre-S or S gene. Several methods have been developed and used for HBV genotyping. This study was undertaken to determine the HBV genotypes in Egyptian pediatric cancer patients with acute and chronic liver disease.</p> <p>Methods</p> <p>HBV genotypes were determined in 22 patients who had acute forms of liver disease (AH) and in 48 patients with chronic active hepatitis (CAH). A type-specific primer based the nested-PCR method was employed in the HBV genotyping.</p> <p>Results</p> <p>This study showed that HBV infections in pediatric cancer patients are attributed predominantly to viral genotypes D and B that constituted 37.1% and 25.7%, respectively of the total infections. In addition, there was a relatively high prevalence of mixed infections of 15.7% among the studied group especially mixed A/D genotype infections. Genotype D was found significantly more often in patients with CAH than in patients with AH [23/48(47.9%) <it>v </it>3/22 (13.6%)].</p> <p>Conclusion</p> <p>These findings show the distribution of HBV A-D genotypes in pediatric cancer Egyptian patients. Furthermore, our results indicate a markedly high prevalence of mixed A/D genotype infections in subjects with CAH and a possible association of mixed infections with the severity of liver diseases.</p

Toxicity of co-exposure of microplastics and lead in African catfish (Clarias gariepinus)

Microplastics (MPs) are an emerging threat to freshwater ecosystems with several ecotoxicological ramifications for fish. Microplastics (MPs) can adsorb heavy metals on their surfaces and increase their availability to aquatic organisms. The combined impact of lead and microplastics on fish has only been studied seldom utilizing a variety of markers. The present study aimed to evaluate the hematological, biochemical, and inflammatory signals (cytokines), as well as antioxidant enzymes in African catfish (Clarias gariepinus) exposed to lead (Pb) and MPs individually and combined for 15 days (acute toxicity experiment). The fish were split into four groups, the first of which was the control group. The second group received exposure to 1 mg/L of lead nitrate [Pb(NO3)2]. The third group was given 100 mg/L of MPs. A solution containing 100 mg/L of MPs and 1 mg/L of lead nitrate [Pb(NO3)2] was administered to the fourth group (the combination group). According to the findings, when MPs and Pb were combined for 15 days, the red blood cells (RBCs), thrombocytes, and lymphocytes were significantly reduced in comparison to the control fish. When compared to the control fish, the fish exposed to MPs and Pb alone or together showed a significant rise in blood interleukin-1β (IL-1β) and interleukin-6 (IL-6) cytokines. Both MPs and Pb exposure in catfish resulted in significant changes in the plasma electrolytes. The fish treated with MPs and Pb individually or in combination showed significant reduction in superoxide dismutase (SOD) and total antioxidant capacity (TAC) levels compared to the control group. The fish exposed to the combined action of MPs and Pb showed a considerable modification in all biochemical markers. The difference in the mean concentration of Pb (mg/L) between the fish exposed to Pb alone and the fish subjected to Pb and MPs combination was not statistically significant. In conclusion, according to this investigation, exposure to Pb caused an insignificant increase in Pb accumulation when MPs were present. However, co-exposure may result in anemia, cellular harm, extremely high levels of oxidative stress, and an inflammatory reaction