The diagnostic significance of circulating lncRNA ADAMTS9-AS2 tumor biomarker in non-small cell lung cancer among the Egyptian population.

BACKGROUND: Long non-coding RNA ADAM metallopeptidase with thrombospondin type 1 motif, 9 antisense RNA 2 (ADAMTS9-AS2) was recognized as a novel tumor suppressor and plays an important role in the initiation and progression of malignant behavior in human cancers, although its plasma expression and clinical value in patients with non-small cell lung cancer (NSCLC) remain unknown. We aimed to analyze the diagnostic role of ADAMTS9-AS2 and cytokeratin 19 fragmentation antigen (CYFRA 21-1) in NSCLC. METHODS: The present study included 80 control subjects, 80 patients with benign lung lesion and 80 NSCLC patients. The expression of ADAMTS9-AS2 in the tissue and plasma was detected by a real-time polymerase chain reaction. Serum CYFRA 21-1 was analyzed using an enzyme-linked immunosorbent assay. RESULTS: In comparison with benign lung lesion and controls, tissue and plasma ADAMTS9-AS2 expression were significantly down-regulated in NSCLC (p < 0.001). Decreased ADAMTS9-AS2 expression was associated with TNM stages in NSCLC patients (p < 0.001). Up-regulation of CYFRA 21-1 was reported among NSCLC patients and it was associated with TNM staging. Tissue and plasma ADAMTS9-AS2 expression levels were the predicting factors for NSCLC and they both correlated negatively with CYFRA 21-1 levels. Plasma ADAMTS9-AS2 levels had a significant positive correlation with their tumor tissue levels. Plasma ADAMTS9-AS2 showed a higher sensitivity (95%) and specificity (99.1%) in the diagnosis of NSCLC than CYFRA 21-1 (61.3% sensitivity and 60% specificity). CONCLUSIONS: Our results suggested that decreased plasma ADAMTS9-AS2 expression might act as a novel non-invasive tumor biomarker in NSCLC diagnosis. Furthermore, plasma ADAMTS9-AS2 might predict aggressive tumor behavior.

Is serum endocan a sensitive biomarker for early recurrence of hepatocellular carcinoma after radiofrequency ablation?

BACKGROUND AND AIM OF THE WORK: Hepatocellular cancer (HCC) is one of the common liver cancers and considered to be the sixth most commonly occurring cancer in the world and the second leading cause of death among cancer patients. More recent studies on HCC showed that the elevated serum endocan level was a predictive factor of recurrence after radiofrequency ablation. The aim of this study is to evaluate the serum endocan level as a prognostic biomarker for recurrence of HCC after percutaneous radiofrequency ablation. PATIENTS AND METHODS: Analytic-prospective study was carried out in Suez Canal University Hospitals. The study was carried out on 80 patients classified into three groups: group 1 (control group) consisted of 20 apparently healthy persons; group 2 consisted of 20 patients with liver cirrhosis; and group 3 consisted of 40 treatment-naive HCC patients who were prepared for radiofrequency ablation. All HCC patients (who were confirmed to have complete ablation after RF) were followed up by using triphasic abdominal CT, serum AFP and serum endocan assessment at 3 and 6 months after radiofrequency ablation. RESULTS: Our study revealed a high level of serum endocan in the HCC group with a statistically significant difference (<0.001) between the three groups. HCC patients had a higher level of serum endocan (6.2 ± 2.25) followed by an liver cirrhosis group (2.0 ± 1.29) and then the control group (1.0 ± 0.3). The serum endocan level had a positive correlation with recurrence of HCC (P < 0.0001). There was a positive correlation between serum endocan and serum alanine transferase (P = 0.02), and a positive correlation between serum endocan and the number of tumors (P = 0.01). CONCLUSION: Serum endocan is considered as a prognostic biomarker for tumor recurrence in HCC patients after radiofrequency ablation.

Nebivolol protects against cyclophosphamide-induced nephrotoxicity through modulation of oxidative stress, inflammation, and apoptosis.

The usefulness of cyclophosphamide (CP) in the treatment of multiple human malignancies and immunological diseases is hindered by the danger of developing nephrotoxicity. The toxic metabolites of CP are suggested to be responsible for oxidative stress resulted from the production of reactive oxygen species (ROS) and stimulation of lipid peroxidation. Nebivolol (NEB) is a third-generation selective B1 adrenoceptor antagonist, but it has also various pharmacological properties such as anti-inflammation, anti-apoptotic, and antioxidant activities. Thus, the present study aims to explore the potential protective effect of NEB against CP-induced nephrotoxicity. A cumulative dose of CP (75 mg/kg) was administered to albino rats by intraperitoneal injection. The protective effect of NEB was investigated by co-administration of NEB (10 mg/kg orally daily). Administration of NEB with CP significantly improved renal functions and reduced the oxidative renal changes induced by CP injection. Co-administration of NEB ameliorated apoptosis and inflammatory markers that were markedly exaggerated by CP. Our results indicated that NEB could be used as a protective agent against CP-induced nephrotoxicity.

Protective effect of tolvaptan against cyclophosphamide-induced nephrotoxicity in rat models.

Cyclophosphamide (CP) is a chemotherapeutic agent which is extensively used in the treatment of multiple neoplastic and nonneoplastic diseases like breast cancer, lymphomas, systemic lupus erythematosus, and multiple sclerosis. Dose-limiting side effects, mainly nephrotoxicity is a major problem hindering its use in the clinical practice. CP induces nephrogenic syndrome of inappropriate antidiuresis mostly via the activation of arginine vasopressin V2 receptors. Moreover, CP produces reactive metabolites which is responsible for augmentation of lipid peroxidation and oxidative stress. Tolvaptan (TOL) is a selective vasopressin V2 receptor antagonist used in the treatment of clinically significant hyponatremia, volume overload in heart failure, and liver cirrhosis with edema. The present study aimed to investigate the potential protective effect of TOL in CP-induced nephrotoxicity. Twenty-four adult male albino rats were randomly divided into four groups: the control group, TOL group that treated daily with tolvaptan (10 mg/kg/d, orally), CP group where CP was administered intraperitoneally 75 mg/kg on days 3, 4, 5, 19, 20, and 21 of study, and the CP + TOL group where animals were treated with TOL daily with (10 mg/kg/d, orally) for 22 days with concomitant administration of CP as described before. Coadministration of TOL with CP induces significant improvement in the level of urine volume, serum Na+, serum osmolarity, urinary creatinine, and free water clearance in addition to significant reduction of body weight, serum creatinine, urea, serum K+, blood pressure, urine osmolarity, and the fractional excretion of sodium as compared to CP-treated group. In addition, coadministration of TOL significantly reduced MDA, the marker of lipid peroxidation, and different pro-inflammatory cytokines. Histopathological changes showed improvement in the signs of nephrotoxicity with the coadministration of TOL. Also, co-treatment with TOL significantly decreased the level of markers of apoptosis as caspase-3 and Bax with increased expression of antiapoptotic Bcl-2 in renal tissue as compared to CP-treated group.

Measurement of serum glutathione peroxidase, catalase and superoxide dismutase concentration in patients with external anogenital warts before and after treatment with intralesional tuberculin purified protein derivative.

External anogenital warts are considered the commonest viral sexually transmitted infection that has serious negative psychological effects on both males and females such as anxiety and marked stress. Aim of this work is to measure serum glutathione peroxidase (GSH-Px), catalase and superoxide dismutase enzyme level in patients with external anogenital warts before and after intralesional tuberculin purified protein derivative (PPD) injection. This study carried out 59 patients with anogenital warts recruited from the dermatology clinic and the andrology clinic, Suez Canal University hospital. Each patient was injected with 10 units (0.2 ml) of PPD intralesionally in the mother or largest wart with 2 weeks interval till complete resolution or maximum of six injections. Serum GSH-Px, catalase and superoxide dismutase were measured using ELISA before and after injection. Results of PPD injection showed that 69.5% of patients were responders while 30.5% were nonresponders. The mean level of serum GSH-Px, catalase and superoxide dismutase dropped significantly after injection with levels pre- and post-injection, 91.1 ng/ml versus 52.6 ng/ml, 88.5 ng/ml versus 67.4 ng/ml and 28.6 ng/ml versus 21.8 ng/ml respectively. Antioxidant enzyme levels decrease significantly after PPD injection. Serum GSH-Px and catalase were significantly related to PPD response.

Community acquired pneumonia among adult patients at an Egyptian university hospital: bacterial etiology, susceptibility profile and evaluation of the response to initial empiric antibiotic therapy.

BACKGROUND: Effective empirical antibiotic therapy for community acquired pneumonia (CAP), based on frequently updated data about the pattern of bacterial distribution and their antimicrobial susceptibilities, is mandatory. AIM: To identify the bacterial etiology of CAP in adults and their antibiotic susceptibility patterns and to evaluate the response to initial empirical antibiotic therapy in an Egyptian university hospital. SETTINGS AND DESIGN: A cross-sectional hospital-based study. PATIENTS AND METHODS: CAP cases were selected by systemic random sampling from those admitted to the chest department. All were evaluated at admission and 4 days after starting empiric therapy. Typical bacteria were isolated, identified and tested for their antibiotic susceptibility. An indirect IF assay was used to diagnose atypical bacteria. Clinical response to initial empiric antibiotic therapy was clinically, laboratory and radiologically evaluated. RESULTS: Two hundred and seventy CAP patients were included. Bacteria represented 50.4% of them. Klebsiella pneumoniae was the most prevalent bacterium (10.37%) followed by Streptococcus pneumoniae and P. aeruginosa (7.78% each). Overall, 76.2% of isolates showed a multidrug resistant phenotype: 82.61% (19/23) S. pneumoniae, 89.66 % (26/29) K. pneumoniae, 65.22% (15/23) Pseudomonas aeruginosa, 87.50% (7/8) Escherichia coli and 81.25 % (13/16) Staphylococcus aureus. Broad spectrum ß-lactams, especially carbapenems, and moxifloxacin showed in vitro efficacy on most of the tested isolates. Forty-three cases (15.9%) were nonresponders, 37 (86%) of them showed bacterial etiology. The highest rate of nonresponsiveness (30.43%) was observed in cases receiving antipseudomonal/antipneumococcal ß-lactam plus a fluoroquinolone for suspected P. aeruginosa infection. CONCLUSION: Multidrug resistance in bacteria causing CAP and high frequency of isolation of hospital pathogens are prominent features of this study. Azithromycin containing regimens were associated with the lowest rates of nonresponsiveness. Development and implementation of an antibiotic stewardship program are highly recommended for CAP management.

T Regulatory Cells Response to Allergen Specific Immunotherapy in Patients with Allergic Airway Diseases: A Prospective Study.

Forkhead box P3 (FoxP3) T regulatory (Treg) cells modulate the immune system by blocking other types of T-cells. They maintain tolerance to self-antigens and help in inducing tolerance to foreign antigens. A deregulation of FoxP3 Tregs seems to play an important role in allergic disorders. The aim of this work was to study the response of FoxP3 Treg cells and their FoxP3 expression in patients, attending the Allergy Unit and the Chest Outpatient Clinic, Faculty of Medicine, Zagazig University, with allergic airway diseases, before and 1 year after receiving subcutaneous allergen specific immunotherapy (SIT). This prospective study was carried out on 25 patients with allergic airway diseases, confirmed by positive skin test, and that showed clinical improvement one year after SIT. All cases were subjected to total immunoglobulin E quantitation by ELISA. FoxP3 Treg cells frequency and FoxP3 relative fluorescence intensity, as an indicator of Tregs function, were assessed by flowcytometry. The results were compared before and after SIT. Twenty five age and sex matched apparently healthy volunteers were enrolled as controls. Our findings demonstrated that in comparison to the control group, the count of FoxP3 T regulatory cells was higher; however, the function was lower among the enrolled patients (P= 0.007 and P< 0.001, respectively). When FoxP3 Tregs were compared in the patients before and one year after SIT, it was found that both the count and FoxP3 expression showed statistically significant increase (P< 0.001). An inverse correlation was found between FoxP3 Tregs count and FoxP3 expression. It is concluded that patients with allergic airway diseases have increased number of FoxP3 Treg cells but with defective function. SIT plays a role in increasing the number of FoxP3 Tregs and improving their suppressive function, which leads to control of airway inflammation and thus clinical improvement.

Surgical treatment of bronchiectasis: a retrospective observational study of 138 patients.

BACKGROUND: We analyzed cases of bronchiectasis; its presentation, etiology, diagnosis, indications for surgery, surgical approach, and the outcome. METHODS: A retrospective analysis of 138 patients who underwent surgery for bronchiectasis. RESULTS: The mean age was 30.2±15.7 years. 55.8% patients were males. Symptoms were recurrent infection with cough in all patients, fetid sputum (79.7%), and hemoptysis (22.5%). The etiology was recurrent childhood infection (38.4%), pneumonia (29%), TB (9.4%), sequestration (4.3%), foreign body obstruction (4.3%), and unknown etiology (14.5%). CXR, CT scan, and bronchoscope were done for all patients. Bronchiectasis was left-sided in (55.1%) of patients. It was mainly confined to the lower lobes either alone (50.7%) or in conjunction with middle lobe or lingual (7.2%). Indications for resection were failure of conservative therapy (71.7%), hemoptysis (15.9%), destroyed lung (8%), and sequestration (4.3%). Surgery was lobectomy (81.2%), bilobectomy (8.7%), and pneumonectomy (8%). Complications occurred in 13% with no operative mortality. 84% of patients had relief of their preoperative symptoms. CONCLUSIONS: Surgery for bronchiectasis can be performed with acceptable morbidity and mortality at any age for localized disease. Proper selection and preparation of the patients and complete resection of the involved sites are required for the optimum control of symptoms and better outcomes.