Spectrophotometric and AAS determination of ramipril and enalapril through ternary complex formation

Two sensitive, spectrophotometric and atomic absorption spectrometric procedures are developed for the determination of two antihypertensive agents (enalapril maleate and ramipril). The spectrophotometric procedures for the two cited drugs are based on ternary complex formation. The first ternary complex (copper(II), eosin, and enalapril) was estimated by two methods; the first depends on its extraction with chloroform measuring at 533.4 nm. Beer's law was obeyed in concentration range from 56 to 112 microg ml(-1). The second method for the same complex depends on its direct measurement after addition of methylcellulose as surfactant at the pH value 5 at 558.8 nm. The concentration range is from 19 to 32 microg ml(-1). The second ternary complex (iron(III), thiocyanate, and ramipril) was extracted with methylene chloride, measuring at 436.6 nm, with a concentration range 60-132 microg ml(-1). The direct atomic absorption spectrometric method through the quantitative determination of copper or iron content of the complex was also investigated for the purpose of enhancing the sensitivity of the determination. The spectrophotometric and atomic absorption spectrometric procedures hold their accuracy and precision well when applied to the determination of ramipril and enalapril dosage forms.     

Long-term results of low-dose-rate interstitial-intracavitary brachytherapy in the treatment of carcinoma of the cervix

PURPOSE: Brachytherapy plays a major role in the treatment of patients with carcinoma of the cervix. However, routine intracavitary brachytherapy may not be feasible or adequate to treat locally advanced disease. The purpose of this retrospective study (spanning a 20-year period) was to determine the outcome of interstitial low-dose-rate brachytherapy in the treatment of bulky or locally advanced cervical cancer. The long-term survival and safety of this technique were evaluated, along with its impact on local and locoregional control, disease-free survival, and complications. METHODS AND MATERIALS: A total of 185 previously untreated patients with cervical cancer were treated between 1977 and 1997. According to the International Federation of Gynecology and Obstetrics classification, 21 patients had Stage IB (barrel), 77 Stage II, 77 Stage III, and 10 Stage IV disease. All patients were treated by a combination of external megavoltage irradiation to the pelvis to a dose of 5040 cGy followed by interstitial-intracavitary implants to a dose of 40-50 Gy to the implanted volume in two applications. RESULTS: Clinical local control was achieved in 152 (82%) of the 185 patients. A 5-year disease-free survival rate of 65%, 67%, 49%, and 17% was achieved for patients with Stage IB, II, III, and IV disease, respectively. Eighteen (10%) of the 185 patients developed Radiation Therapy Oncology Group Grade 3 or 4 late complications. CONCLUSION: Patients with locally advanced cervical cancer, or with distorted anatomy, may be treated adequately with interstitial brachytherapy to achieve excellent locoregional control and a reasonable chance of cure with acceptable morbidity.     

The effect of adenoidectomy on right ventricular performance in children

Objective

Several studies have shown a reduction in pulmonary artery pressure (PAP) after adenoidectomy in children suffering form upper airway obstruction caused by adenoid hypertrophy (AH). However, it is not clear whether this would be significantly reflected on right ventricle output (RVO).

Methods

Our aim was to determine if there were any detectable changes in RV performance parameters after adenoidectomy in children with AH. Thirty children with AH (female/male: 11/19) aged between 2.5 and 12 years (median: five years) were included in this study. Adenoidectomy was performed under sinuscopic guide using adenoid curette and microdebrider. All children were examined by echocardiography one day before and one month after adenoidectomy. Velocity time integral of tricuspid valve flow (VTItv) and pulmonary valve flow (VTIpa); E/A ratio of tricuspid valve flow; RV end-diastolic diameter (RVEDd) and left ventricle fraction shortening (FS) were measured. Heart rate (HR) was also recorded.

Results

Preoperatively VTItv, VTIpa, E/A ratio, RVEDd, FS, and HR were 18.6 ± 3.0 cm, 20.8 ± 3.1 cm, 1.21 ± 0.31, 11.5 ± 2.1 mm, 35.1 ± 4.3%, and 112 ± 19, respectively. Postoperatively VTItv, VTIpa, E/A ratio, RVEDd, FS, and HR were 21.5 ± 2.5 cm, 24.4 ± 4.3 cm, 1.44 ± 0.32, 9.3 ± 2.6 mm, 33.9 ± 3.5%, and 104 ± 28, respectively. There were significant differences between preoperative and postoperative VTItv (p = 0.03), VTIpa (p = 0.01), E/A ratios (p = 0.04), and RVEDd (p = 0.01). FS and HR were not significantly different.

Conclusions

This study illustrated that in children suffering from AH, relieving upper airway obstruction by adenoidectomy may result in improvement of RV filling and RVO, associated with the reduction in PAP.     

Design,synthesis, and molecular docking study of new monastrol analogues as kinesin spindle protein inhibitors

Lung, colorectal, and breast cancers are the top three types of cancer by incidence and are responsible for one-third of the cancer incidence and mortality. A series of 18 3,4-dihydropyrimidine analogues bearing a 1,2-methylenedioxybenzene component at position 4 with diverse side chains at positions 5 and 6 was designed and synthesized as inhibitors of the Eg5 kinesin enzyme. Target compounds were screened for their anticancer activity according to the NCI-USA protocol toward a panel of 60 cancer cell lines. Compounds 12a and 12b displayed the best antiproliferation activity against many cell lines. Interestingly, compound 12a displayed lethal effects against non-small-cell lung cancer NCI-H522 cells (−42.26%) and MDA-MB-468 breast cancer cells (−1.10%) at a single-dose assay concentration of 10⁻⁵ M. Compounds 11c, 11d, 11g, 12a – d, 13, 15 , and 18a were assayed against the kinesin enzyme, with IC₅₀ values ranging from 1.2 to 18.71 μM, which were more potent compared with monastrol (IC₅₀ = 20 μM). Cell cycle analysis of NCI-H522 cells treated with compound 12a showed cell cycle arrest at the G2/M phase. Furthermore, the expression levels of active caspase-3 and -9 were measured. A molecular docking study was performed for some demonstrative compounds as well as monastrol docked into the allosteric binding site of the kinesin spindle protein.     

Managing diabetes and liver disease association

There is strong association between liver diseases and diabetes (DM) which is higher than expected by a chance association of two very common disorders. It can be classified into three categories: Liver disease related to diabetes, hepatogenous diabetes (HD), and liver disease occurring coincidentally with DM. The criteria for the diagnosis of diabetes associating liver disease are the same for primary diabetes. Two hours post glucose load is a better screening test for HD. HbA1c may not be suitable for diagnosis or monitoring of diabetes associating advanced liver disease. Apart from the increased cardiovascular risk in patients with type 2 DM (T2 DM) and NAFLD, the cardiovascular and retinopathy risk is low in HD. Patients with metabolic derangement should be screened for NAFLD which in turn may predict T2 DM development. Similarly, patients with established T2 DM should also be screened for NAFLD which further contributes to diabetes worsening.Diabetes is a significant risk factor for progression of the chronic liver disease. It is associated with poor patient survival.Treatment of diabetes associating liver disease appears beneficial. Metformin, if tolerated and not contraindicated, is recommended as a first-line therapy for patients with diabetes and chronic liver disease (CLD). If the hepatic disease is severe, insulin secretagogues should be avoided because of the increased risk of hypoglycaemia. Pioglitazone may be useful in patients with fatty liver disease. DPP-4 inhibitors showed effectiveness and safety for the treatment of T2 DM in CLD patients up to those with child B stage. GLP-1 receptor agonists and SGLT-2 inhibitors exhibit positive effects on weight and are associated with minimal risk of hypoglycaemia. Insulin must be used with caution, as hypoglycaemia may be a problem. Insulin analogues are preferred in the context of hypoglycaemiaStatins can be used to treat dyslipidaemia in NAFLD, also the use of angiotensin II receptor antagonist for hypertension is safe and beneficialGiven the clear association between diabetes mellitus and hepatocellular carcinoma, the strict control of glycaemia with insulin sensitizers can be essential in its prevention.The addition of DM to the currently used scores (Child-Pugh and MELD scores) may enhance the sensitivity and the specificity for prediction of morbidity and mortality rates in cirrhotic patients.In the new era of directly acting antiviral agents (DAAs) for HCV treatment, it is recommended to follow up lipid profile and blood sugar levels following SVR in order to adjust doses of medications used in diabetic (SVR is associated with reduction in insulin requirements) and dyslipidaemic patients (rebound increase in the lipid profile after clearing the virus may increase risk of cardiovascular disease (CVD)). The issues of post liver transplant diabetes and relation between DM and chronic HBV are highlighted.This narrative review and Consensus-based practice guidance (under revision and criticism) are based on a formal review and analysis of the recently published world literature on the topic (Medline search up to September 2017); and the experience of the authors and independent reviewers.     

Flow cytometric detection of leukemic stem cells (LSCs) in Egyptian pediatric B-acute lymphoblastic leukemia

Identifying leukemia stem cells (LSCs) is a challenge and a critical step in understanding their respective biology and may provide insights into a more efficient treatment of acute lymphoblastic leukemia (ALL). This cohort study aimed at detecting LSCs expressing CD19, CD34, and CD38^Low in the bone marrow of 20 de novo Egyptian pediatric B-ALL patients at the time of the diagnosis and after the induction of chemotherapy. LSCs were detected in 80% of cases at the time of diagnosis and in 70% of the cases after the induction of chemotherapy. Patients were followed up for 12–18?months. No statistically significance difference was encountered between LSC-positive and LSC-negative patients as regards their clinical and laboratory data at the time of diagnosis. Furthermore, there was no statistically significant difference between the percentages of LSC-positive patients before or after induction of therapy. On follow-up, two patients died; they had residual LSCs after the induction therapy. However, the existence of LSCs did not affect the patient's 1-year disease-free survival rate. LSC may resist the traditional lines of treatment applied for childhood B-ALL; it may be used in minimal residual disease monitoring as well as being a target for new therapeutic lines to improve the outcome of treatment especially in patients with high-risk and relapsed ALL.     

Role of MRI in evaluation of hip joint involvement in juvenile idiopathic arthritis

Aim of the WorkTo evaluate the role of MRI in diagnosing hip arthritis and correlating it with clinical and laboratory assessments in juvenile idiopathic arthritis (JIA).Patients and MethodsThe study included 30 patients with JIA with mean age of 13.5 ± 4.5. Disease activity was evaluated by DAS28 score, physician’s global assessment (PGA–VAS), patient’s global assessment (VASglobal) and the assessment of functional ability by (CHAQ). Hip joint evaluation was assessed by hip pain on movement and the degree of limitation of motion (score 0–3). Plain radiography and MRI of the hip joint were performed for all patients. MRI score was done.ResultsMRI of hips was abnormal in 12 (40%) of all patients: 2/8 (25%) of the oligoarticular group, 4/13 (30.8%) of the polyarticular group, 5/7 (71.4%) of the systemic onset group and 1/2(50%) of the enthesitis related group. Comparing mean values of MR scores of the four clinical subsets showed significant difference (p < 0.001). Patients with active disease showed higher MR scores (3.7 ± 1.5) than those with inactive disease (2.1 ± .9) [p < 0.002]. Presence of effusion and gadolinium enhancement were significantly higher in active hips (p < 0.01 and p < 0.001 respectively). VAS–PGA and ESR were significantly correlated with MRI score (p < 0.02 and <0.05 respectively).ConclusionMRI of the hip plays an important role in the study of patients with JIA as it reveals early joint involvement and evaluates the extent of joint disease. This permits intervention at an appropriate time with suitable treatment. Clinical and laboratory findings are inadequate diagnostic tools for the assessment of hip arthritis when comparing with MRI.     

Progressive systemic sclerosis in Egyptian patients: Clinical characteristics and nail fold capillaroscopy

Aim of the work

To present the clinical and laboratory disease characteristics in Egyptian patients with progressive systemic sclerosis (SSc) and their nail fold capillaroscopy findings.