Synthesis of furodiketochroman and bis-furocoumarin derivatives and their biological activity

A number of substituted furodiketochroman derivatives (III _a-f ) have been synthesized by fusion of aromatic aldehydes with 5-hydroxybergapten and 5-hydroxyisopimpinellin. On the other hand, when the reaction was carried out in a solvent, the corresponding bis-furocoumarin derivatives (IV _c-n ) were obtained. The anticoagulant effect of compoundsIII _a,b,d andIV _b,c,f,g,i,k , was tested. They failed to demonstrate any significant effect. The effect of the tested compounds on the arterial blood pressure was studied. CompoundsIV _c ,III _d ,III _b ,IV _b ,IV _g ,IV _k andIV _i showed lowering effects on the normal systolic blood pressure of anaesthetized rats in a decreasing manner.     

Effects of depressed mood versus clinical depression on neuropsychological test performance among African American men impacted by HIV/AIDS

The utility of self-report measures in identifying those at risk for depressive disorder and the adverse impact of depression versus depressed mood and HIV serostatus on neuropsychological (NP) test performance were examined in a large sample (N = 243) of gay and bisexual African American men. Results indicate high rates of depression relative to recent population estimates, regardless of methodology, but that the use of standard cut-scores for self-report inventories may significantly overestimate psychiatric morbidity. Limited independent effects of serostatus or depression on NP test performance were observed. More importantly, a complex set of adverse effects of depression and its interaction with serostatus which varied according to the methodology used to assess depression were observed. These findings are discussed in light of ongoing controversy regarding the relative influence of depression on neuropsychological functioning among people living with HIV/AIDS.     

Effect of Zr and Ti Addition and Aging Treatment on the Microstructure and Tensile Properties of Al-2%Cu-Based Alloys

The present work investigated the effect of aging treatment on the microstructure and tensile properties of an Al-2%Cu base alloy containing various additions of Zr and other alloying elements. Aging was carried out at temperatures of 180–300 °C for different aging times at each temperature. The tensile properties indicated that Zr additions improved the strength of the base alloy, especially at high Zr levels at 180 °C. At the 220 °C aging temperature, however, while Zr addition did not have a beneficial effect on the alloy strength, the ductility was found to improve. Zr-Ti combined additions had a significant effect on the microstructure of the base alloy, as the morphology of the α-Al grains transformed into a non-dendritic morphology, and the grain size decreased sharply. These effects were at their maximum at 180 °C and 0.5 wt% Zr addition. Moreover, the Zr-containing alloys aged at higher temperatures, such as 220 °C and 240 °C, maintained a noticeably higher level of strength over the base alloy aged at the same temperatures. Quality index charts based on the tensile test data also reflected an improvement in alloy quality and strength with Zr-Ti combined additions.     

The nature of intrauterine adhesions following reproductive hysteroscopic surgery as determined by early and late follow-up hysteroscopy: clinical implications

Objective To evaluate the rate and characteristics of postoperative intrauterine adhesions (IUA) that might be formed following hysteroscopic reproductive surgery from both a gross and a histologic perspective as determined by early and late follow-up diagnostic hysteroscopy. Methods Retrospective analysis of 61 women wishing a pregnancy and suffering from a significant intrauterine pathology affecting their reproductive outcome were reviewed. All patients were treated hysteroscopically. Subsequently, they were randomly assigned to perform a follow-up diagnostic hysteroscopy at a variable intervals from their initial surgery. Multiple hysteroscopic-guided biopsies from IUA, when present, were obtained in several cases. Twenty patients were in the early group and had follow-up hysteroscopy performed 2–4 weeks after the initial operation. The late diagnostic group consisted of 41 patients with follow-up hysteroscopy at about 12 months (8–16 months). The two groups were similar to composition. Postoperatively, none of the early diagnostic group underwent hysterosalpingography (HSG) whereas all of the late group performed HSG 4 months following the initial surgery, which showed at least one-third of the cavity free of adhesions. When adhesions were present, no effort was made to lyse them. Results At follow-up hysteroscopy, 25% of both groups had no significant adhesions. Grade I adhesions (thin, filmy) occurred in 60% of the early hysteroscopy patients and in only 12% of the late group (P < 0.05). Grade II adhesions were present in 10% of the early group and in up to 41% in the late group (P < 0.05), whereas Grade III adhesions were present in only 5% of the early hysteroscopy group, but in 22% of the late one (P < 0.05). Correlation between hysteroscopic and histologic findings were good in most of cases in both groups. Follow-up to determine the subsequent reproductive outcome revealed similar conception rates in both groups. Conclusion The IUA that might be formed immediately following hysteroscopic reproductive surgery are histologically different from those appearing a longer time after the original operation. Routine early follow-up hysteroscopy can influence the prognosis resulting from the original surgery.     

Analysis of anti‐apoptotic PVT1 oncogene and apoptosis‐related proteins (p53, Bcl2, PD‐1, and PD‐L1) expression in thyroid carcinoma

BackgroundAn aberrant expression of long non‐coding RNA PVT1 has been associated with apoptosis in various cancer types. We aimed to explore the PVT1 and four apoptosis‐related proteins (p53, Bcl2, and PD‐1/PD‐L1) signature in thyroid cancer (TC).MethodsThe PVT1 expression level was measured in 64 FFPE TC paired samples by real‐time quantitative PCR. Overall and stratified analyses by different clinicopathological features were done. The apoptotic proteins were evaluated by immunohistochemistry staining.ResultsOverall analysis showed significant PVT1upregulation in TC tissues (p < 0.001). Similarly, subgroup analysis by BRAF ^V600E mutation showed consistent results. Lower expression of p53 was associated with mortality (p = 0.001). Bcl2 overexpression was associated with greater tumor size (p = 0.005). At the same time, HCV‐positive cases were associated with repressed Bcl2 expression levels (54.3% in HCV‐negative vs. 6.9% in HCV‐positive cases, p = 0.011). PD‐1 expression was associated with lymph node metastasis (p = 0.004). Enhanced PD‐L1 expression in the tumor was associated with a higher tumor stage, lymphovascular invasion, and mortality risk. Kaplan–Meier curves for overall survival showed that low p53 and high PD‐L1 expressions were associated with lower survival time. The p53‐positive staining is associated with a 90% decreased mortality risk (HR = 0.10, 95%CI = 0.02–0.47, p = 0.001), while patients with high PD‐L1 were five times more likely to die (HR = 4.74, 95%CI = 1.2–18.7, p = 0.027).ConclusionOur results confirm the upregulation of PVT1 in TC. The apoptosis‐related proteins (p53, Bcl2, and PD‐1/PD‐L1) showed different prognostic utility in TC patients; in particular, low p53 and high PD‐L1 expressions associated with low survival times. Further large‐scale and mechanistic studies are warranted.     

Long-term (4 year) efficacy and tolerability of doxazosin for the treatment of concurrent benign prostatic hyperplasia and hypertension

BACKGROUND: The alpha1-adrenoceptor antagonist doxazosin has proved successful in treating patients with concurrent benign prostatic hyperplasia (BPH) and hypertension in short-term studies. However, both conditions are chronic and may worsen over time. The aim of this study was, therefore, to examine the tolerability and efficacy of doxazosin in the long-term treatment of concurrent BPH and hypertension. METHODS: This study was a longitudinal extension of earlier double-blind trials. Patients were enrolled into the study on a rolling basis. From a total of 178 BPH patients with hypertension enrolled into the study, 28 had reached 48 months of open-label treatment with doxazosin at the time of the final data cutoff. RESULTS: Treatment with doxazosin resulted in sustained benefits for BPH patients over the whole study period, with significant improvements in the severity (12.2%, P < 0.001) and bothersomeness (13.2%, P < 0.001) of BPH symptoms, and in the maximum urinary flow rate (26.6%, P < 0.05) from baseline to the end of the 4-year period. There was also a significant and sustained reduction in diastolic blood pressure. The efficacy of doxazosin treatment for both BPH and hypertension was maintained over the 4-year period, despite the tendency of these conditions to worsen with time. Comparison of adverse events in patients with long- and short-term hypertension and BPH demonstrates that the safety of doxazosin is not altered during long-term therapy. CONCLUSIONS: This study demonstrates that doxazosin appears to be well tolerated and efficacious in the long-term management of concurrent BPH and hypertension.     

Investigation of mtDNA control region sequences in an Egyptian population sample

The sequences of mitochondrial DNA (mtDNA) control region were investigated in 101 unrelated individuals living in the northern region of Nile delta (Gharbia, N = 55 and Kafrelsheikh, N = 46). DNA was extracted from blood stained filter papers or buccal swabs. HV1, HV2 and HV3 were PCR amplified and sequenced; the resulted sequences were aligned and compared with revised Cambridge sequence (rCRS). The results revealed presence of total 93 different haplotypes, 86 of them are unique and 7 are shared haplotypes, the most common haplotype, was observed with a frequency, 2.97% of population sample. High mtDNA diversity was observed with genetic diversity and power of discrimination, 0.9982 and 0.9883, respectively. In this dataset the west Eurasian haplogroups predominated over the African haplogroups. The results would be useful for forensic examinations and human genetic studies.     

Effect of the oral antibilharzial niridazole (ambilhar) on patients with concomitant schistosomiasis and HBs antigenaemia

Twenty-three patients received oral antibilharzial therapy in the form of niridazole tablets (10 mg/kg body weight for 20 days), and 10 patients served as controls. Three months post-therapy, 14 out of 23 treated patients (61%) had cleared the HBsAg. This was found to be statistically significant. In contrast, 2 of the controls (20%) had eliminated the HBsAg from the serum. It is concluded that patients suffering from concomitant schistosomiasis and HBs antigenaemia are enabled to eliminate the HBsAg after niridazole therapy.