Synthesis,in vivo and in silico evaluation of novel 2,3-dihydroquinazolin-4(1H)-one derivatives as potential anticonvulsant agents

In light of the pharmacophoric structural requirements for achieving anticonvulsant activity, a series of N-(1-methyl-4-oxo-2-un/substituted-1,2-dihydroquinazolin-3[4H]-yl)benzamide (4a-g) and N-(1-methyl-4-oxo-2-un/substituted-1,2-dihydroquinazolin-3[4H]-yl)-2-phenylacetamide (4h-n) derivatives were synthesized in two steps starting from the reaction of N-methyl isatoic anhydride with the appropriate hydrazide and followed by condensation with the appropriate aldehyde. The anticonvulsant activities of the synthesized compounds were evaluated according to the anticonvulsant drug development (ADD) programme protocol. Among the synthesized compounds, 4n showed promising activity in both the maximal electroshock (MES) and pentylenetetrazole (PTZ) tests with median effective dose (ED₅₀) values of 40.7 and 6 mg/kg, respectively. The six most promising derivatives, 4b , 4a , 4c , 4f , 4j , and 4i , showed very low ED₅₀ values in the PTZ test (3.1, 4.96, 8.68, 9.89, 12, and 13.53 mg/kg, respectively). All the tested compounds showed no to low neurotoxicity in the rotarod test with a wide therapeutic index. Docking studies of compound 4n suggested that GABA_A binding could be the mechanism of action of these derivatives. The in silico drug likeliness parameters indicated that none of the designed compounds violate Lipinski's rule of five and that they are able to cross the blood–brain barrier.

Densitometer type and impact on risk assessment for osteoporosis.

Studies have shown a high correlation between measurements of bone mineral density (BMD) obtained on differentdual-energy X-ray absorptiometry machines. Challenger osteodensitometers (Diagnostic Medical System [DMS],Montpellier, France) are becoming widely used but little is known about their clinical performance. The aim of this study was to compare BMD measurements and the resulting patient classification based on T-scores obtained on a DMS Challenger device to those obtained on Hologic 4500A (Bedford, MA) device. Fifty-three volunteers were studied.The BMD of the spine and of the hip were simultaneously measured on both densitometers. BMD values obtained on the Challenger were significantly higher than those obtained with the Hologic QDR4500 (p<0.001). The correlations coefficients between the Hologic QDR4500 and the DMS Challenger measured BMDs were r=0.70 at the femoral neck, r=0.70 at the trochanter, and r=0.83 at the spine (p<0.001). Among the 35 postmenopausal women, there was discordance in the WHO T-score-based classification in 28 subjects (80%) at the spine, 18 subjects (52%) at the femoral neck, and 14 subjects (42%) at the trochanter. The intermachine agreement was low: The kappa score was -0.10 at the spine, 0.2 at the femoral neck, and 0.3 at the trochanter. In conclusion, this study cautions against the use of non established densitometers that leads to underdiagnosis of patients and, subsequently, to inappropriate treatment strategies.     

Rosai-Dorfman Disease: A previously unreported association with Sickle Cell Disease

Background  

Rosai-Dorfman Disease is an uncommon benign systemic histio-proliferative disease. This is the first time the disease, although more common in people of African descent, is described in association with Sickle cell disease.     

Human papillomavirus infection in Egyptian esophageal carcinoma: correlation with p53, p21, mdm2, C-erbB2 and impact on survival

The etiological role of human papillomavirus (HPV) in esophageal carcinoma (EC) in relation to p53, mdm2, p21(waf), c-erbB2 and the overall survival (OS) rate was investigated. Tumor and normal tissues from 50 EC were evaluated by polymerase chain reaction and InnoLiPA for HPV. Single strand conformation polymorphism/sequencing were used to detect p53 gene mutations. Immunohistochemistry was performed to determine p53, mdm2, p21(waf)and c-erbB2 expression. Human papillomavirus was detected in 54% of tumors and in 24% of normal tissues. p53, mdm2 and c-erbB2 overexpression was detected in 68%, 70% and 60% of tumors and in 14%, 16% and 10% of normal samples, whereas loss of p21(waf) was evident in 64% of tumors. p53 mutations were detected in 20% of cases. Exon 8 and 5 showed the highest mutation rate (40% each), followed by exons 6 and 7 (10% each). There was a significant correlation between HPV and p53, mdm2, c-erbB2 overexpression. The OS was significantly associated with overexpression of p53 and loss of p21(waf). Human papillomavirus infection is frequent in Egyptian EC. Both p53-dependent and p53-independent pathways seem to be involved in HPV-associated EC. mdm2 and c-erbB2 are possible targets for HPV in the p53-independent pathway. However, only advanced stage and aberrant expression of p53 and p21(waf) are independent prognostic markers.     

Five year study of prenatal testing for Huntington''s disease: demand, attitudes, and psychological assessment.

Adult predictive and prenatal testing programmes for Huntington's disease (HD) in Canada have been available since 1986. However, the demand for prenatal testing and the reasons why some people choose not to have the prenatal test for this late onset disorder have not been well documented. In addition, the knowledge and attitudes of adult predictive testing candidates and their partners about prenatal testing are not well known nor are the psychological effects of prenatal testing well understood. As of September 1991, 425 subjects had entered the Canadian Collaborative Study of Predictive Testing and, of these, 47 subjects or their partners had become pregnant. Of this group, 14 (30%) couples requested prenatal testing, 24 (51%) couples did not want prenatal testing, and nine (19%) at risk subjects had already received a decreased risk through adult predictive testing and, therefore, were not eligible for the prenatal test. Of the 14 couples who initially requested prenatal testing, seven withdrew. Thus, demand for the prenatal test by eligible candidates was 7/38 or 18%, which is much lower than the 32 to 65% expected based on early survey data. The most frequently cited reason for declining prenatal testing was the hope that a cure would be found in time for their children. While the majority of adult predictive testing candidates (71%) in our study had accurate information about definitive prenatal testing, many (63%) did not have a correct understanding of exclusion prenatal testing. Although no serious adverse events such as suicide planning or admission to psychiatric hospital have occurred, a particular need for careful counselling was identified for those at risk candidates and their partners who have one prenatal test and feel compelled to use the test again in future pregnancies. Even though prenatal testing for HD is not requested as often originally expected, it still remains a desired option for some at risk persons and their partners.     

REM sleep deprivation inhibits LTP in vivo in area CA1 of rat hippocampus

Rapid eye movement (REM) sleep deprivation has previously been shown to interfere with normal learning and memory and to inhibit long-term potentiation (LTP) in vitro. Previous studies on REM sleep deprivation and LTP have relied on in vitro analysis in isolated brain slices taken from animals following several days of sleep deprivation. LTP in the hippocampus in situ may differ from LTP in vitro due to modulatory inputs from other brain regions, which are altered after REM sleep deprivation. Here, we examined LTP in unanesthetized, behaving animals on the first and second recovery days following REM sleep deprivation to determine if similar effects are seen in vivo as previously reported in vitro. We found that LTP was significantly impaired in REM sleep-deprived animals on the second recovery day but not the first recovery day. Our results extend previous findings by showing that REM sleep deprivation continues to affect hippocampal function for more than 24h following the end of deprivation. Our results also suggest the presence of a modulatory process not present in vitro. Our findings are not explained by stress during REM sleep deprivation because equivalent circulating corticosterone levels (an index of stress) were found during both REM sleep deprivation and control treatment.     

Selective isolation of fluorescent and nonfluorescent Pseudomonas species from Sohag Governorate (Upper Egypt).

Three hundred and fourty nine isolates belonging to ten different species of Pseudomonas were isolated and identified from soil and water samples on four selective isolation media: Modified Trypticase soy agar (TSA), ACC-agar containing ampicillin-chloramphenicol-cycloheximide, Nitrate plus organic acid agar and Tryptophan substrate agar. The fluorescent species were P. putida (21.2% of the total Pseudomonas species), P. fluorescens (15.8%), P. aeruginosa (9.7%) and P. aureobaciens (2.6%), while the nonfluorescent species were P. stutzeri (12.4%), P. alcaligenes (11.2%), P. pseudoalcaligenes (9.5%), P. mendocina (8.3%), P. lemoignei (5.7%) and P. ruhlandii (3.4%). Modified TSA and ACC media were efficient for the isolation of both fluorescent and nonfluorescent species, whereas Nitrate and Tryptophan media were more selective for the isolation of nonfluorescent species. The optimum temperature for the isolation of different species ranged between 20 degrees and 37 degrees C.     

Finite Element Analysis of Self-Healing Concrete Beams Using Bacteria

Deterioration or crack formation in concrete elements is a phenomenon that cannot be easily avoided, and it has a high cost of repair. A modern technology that needs wider study is the use of the bio-precipitation of calcium carbonate using bacteria to increase a structures’ capacity. The current research presents an analytical study on self-healing concrete beams using bacteria to enhance the beam’s capacity. A Finite Element Analysis on (ANSYS 15.0) was carried out to study the effect of the bacteria concentration (the weight of bacteria to cement weight 1%, 2%, and 3%), the type of bacteria (Bacillus subtilis, E. coli, and Pseudomonas sps.), and the loading (a one-point load, a two-point load, and a distributed load on four points) on concrete beams. Two beams were chosen from previous experimental research and simulated on the ANSYS before carrying out our parametric study to verify the validity of our simulation. Following this, our parametric study was carried out on eight beams; each beam was loaded gradually up to failure. The results show that the optimum type of bacteria was the Bacillus subtilis, and that the bacteria concentration of 3% for Bacillus subtilis can increase the beam’s capacity by 20.2%. Also, we found that distributing the load to four points led to the increase of the beam’s capacity by 74.5% more than the beam with a one-point load.     

Uxoricide by a schizophrenic patient with delusional misidentification syndromes: A case report

Delusional misidentification syndromes in psychiatric disorders might result in dangerous behavior leading sometimes to homicide. An early diagnosis and thorough follow up is important to avoid such consequences.