New series of fused pyrazolopyridines: Synthesis, molecular modeling, antimicrobial, antiquorum-sensing and antitumor activities.

New series of fused pyrazolopyridines were prepared and assessed for antimicrobial, antiquorum-sensing and antitumor activities. Antimicrobial evaluation toward selected Gram-positive bacteria, Gram-negative bacteria and fungi indicated that 5-phenylpyrazolopyridotriazinone 4a has good and broad-spectrum antimicrobial activity. In addition, 5-(4-chlorophenyl)pyrazolopyridotriazinone 4b and 5-(4-(dimethylamino)phenyl)pyrazolopyridotriazinone 4c exhibited good activity against the selected Gram-positive bacteria and A. fumigatus, whereas 5-amino-4-phenylpyrazolopyridopyrimidine 6a demonstrated good activity against B. cereus and P. aeruginosa. Furthermore, 6-amino-5-imino-4-phenylpyrazolopyridopyrimidine 7a and 6-amino-4-(4-chlorophenyl)-5-iminopyrazolopyridopyrimidine 7b demonstrated promising activity against the tested Gram-negative bacteria and fungi, and moderate activity against Gram-positive bacteria. Antiquorum-sensing screening over C. violaceum illustrated that 4a, 6a and 7a-c have strong activity. In vitro antiproliferative assessment of the new derivatives against HepG2, HCT-116 and MCF-7 cancer cells revealed that 7a is the most active analog against all tested cell lines. Likewise, 3,7-dimethyl-4-phenylpyrazolopyridopyrimidinone 2a and 6-amino-4-(4-chlorophenyl)-5-iminopyrazolopyridopyrimidine 7b manifested strong activity against all examined cell lines. In vivo antitumor testing of 2a, 7a and 7b against EAC cells in mice indicated that 7a has the highest activity. Cytotoxicity toward WI38 and WISH normal cells was also assessed and results assured that all of the investigated analogs have lower cytotoxicity than doxorubicin. DNA-binding affinity and topoisomerase IIß inhibitory activity were evaluated, and results revealed that 5b, 7a and 7b bind strongly to DNA; in addition, 2a, 4a, 7a and 7b manifested higher topoisomerase IIß inhibitory activity than that of doxorubicin. Analogs 5b, 7a and 7b were docked into topoisomerase IIß, and results indicated that 7a and 7b have the highest binding affinity toward topoisomerase IIß. In silico simulation studies referred that most of the new analogs comply with the optimum needs for good oral absorption. Also, computational carcinogenicity evaluation was predicted.

Synthesis, molecular modeling and biological evaluation of new pyrazolo[3,4-b]pyridine analogs as potential antimicrobial, antiquorum-sensing and anticancer agents.

New pyrazolo[3,4-b]pyridine analogs 2-9 were synthesized and subjected to antimicrobial testing toward chosen Gram-negative bacteria, Gram-positive bacteria and fungi. Compound 2 exhibited potent and extended-spectrum antimicrobial activity. Further, 6 and 9c demonstrated remarkable and extended-spectrum antibacterial activity. Antiquorum-sensing activity of the new members was tested over C. violaceum, whereas 9c demonstrated strong efficacy, while 2, 8b and 9b displayed moderate efficacy. In vitro anticancer assay toward HepG2, MCF-7 and Hela cancer cells manifested that 2 and 9c are powerful and extended-spectrum anticancer agents. Additionally, 8a, 8b and 9b showed excellent activity toward the three cancer cells. In vivo anticancer assay over EAC in mice indicated that 2 and 9c have the greatest activity. Moreover, cytotoxicity assay over WISH and W138 normal cells clarified that the checked analogs possess weak cytotoxicity toward the two normal cells. DNA-binding affinity was also tested, whereas 2, 3, 8b, 9b and 9c demonstrated great affinity. Molecular modeling studies revealed that the investigated compounds bind to DNA through intercalation similarly to doxorubicin. In silico studies revealed that the new members are anticipated to show excellent intestinal absorption.

The infantile visceral leishmaniasis: could it attack Egyptian north coastal region again?

Visceral leishmaniasis is caused by three species of the L. donovani complex: L. donovani, L. infantum, and L. chagasi. Infections with these organisms are often asymptomatic or very mild, but in a minority of individuals there is progression to severe symptomatic disease. This is associated with spread of the infection throughout the reticuloendothelial system. L. infantum typically affect children below the age of 5 years. However, IVL can also occur in immunosuppressed adults, such as transplant recipients and patients receiving immunosuppressive chemotherapy or patients suffering from chronic intestinal schistosomiasis. IVL was encountered in Al-Agamy, Alexandria on 1983 with Phlebotomus langeroni. This vector is still abundant with low density away from Al-Agamy. Urbanization of the north coastal area in the vicinity of Alexandria changes the ecological status but how does it affect the behavior of sandflies; mainly the IVL vector Phlebotomus langeroni? Many employees and their families return home from Libya with fever with or without other accompanying symptoms. Fever can be a manifestation of a minor, self-limited process or can herald a progressive, life-threatening illness. The detection of Phlebotomus langeroni in El-Hamam City, Sedi Barany City, and Matrooh City and the abundance P. papatasii in these three cities in addition to Al Agamy must be taken into consideration of the Public Health Authority.

Is plague a problem in the Egyptians returning back from Libya?

Many employees return home with fever with or without other accompanying symptoms. Fever can be a manifestation of a minor, self-limited process or can herald a progressive, life-threatening illness. The assessment of this group is often hampered by the clinician's lack of familiarity with the types of infections that the patient may have encountered while traveling. The evaluation of such patients should focus on: What infections are possible given where the patient has lived or traveled and the time when exposures may have occurred? Which of these infections is more probable given the patient's clinical findings and potential exposures? Which of these infections is treatable or transmissible or both? On the other hand, the outbreak of plague at the Libyan-Egyptian borders and the high density rodents and their ecto-parasitic fleas in many Egyptian governorates should be embarked a control program to rodents and fleas and to raise the awareness of the concerned authorizes.

Limited value of annual tuberculosis symptom reminders for health care workers.

BACKGROUND: (UK) National Institute for Health and Clinical Excellence tuberculosis (TB) guidance (2006) recommends that occupational health services send annual TB symptom reminders to staff at increased risk of occupational TB exposure. AIMS: To evaluate the effectiveness of annual TB symptom reminders. METHODS: Retrospective analysis of returns from 4 years' annual TB symptom reminders compared with numbers of hospital staff diagnosed with active TB in the same time period. RESULTS: There were 405 responses to symptom reminders received during the period studied that represented a response rate of 16%. None of the respondents declared TB symptoms. Twelve staff were diagnosed with active TB over the same period. From their work location, only two of these would have received TB symptom reminders according to local TB policy. CONCLUSIONS: Annual TB symptom reminders as currently used result in little direct benefit.

The effect of shredding and test apparatus size on compressibility and strength parameters of degraded municipal solid waste.

In many situations, MSW components are processed and shredded before use in laboratory experiments using conventional soil testing apparatus. However, shredding MSW material may affect the target property to be measured. The objective of this study is to contribute to the understanding of the effect of shredding of MSW on the measured compressibility and strength properties. It is hypothesized that measured properties can be correlated to an R-value, the ratio of waste particle size to apparatus size. Results from oedometer tests, conducted on 63.5 mm, 100 mm, 200 mm diameter apparatus, indicated the dependency of the compressibility parameters on R-value. The compressibility parameters are similar for the same R-value even though the apparatus size varies. The results using same apparatus size with variable R-values indicated that shredding of MSW mainly affects initial compression. Creep and biological strain rate of the tested MSW are not significantly affected by R-value. The shear strength is affected by shredding as the light-weight reinforcing materials are shredded into smaller pieces during specimen preparation. For example, the measured friction angles are 32 degrees and 27 degrees for maximum particle sizes of 50 mm and 25 mm, respectively. The larger MSW components in the specimen provide better reinforcing contribution. This conclusion is however dependent on comparing specimen at the same level of degradation since shear strength is also a function of extent of degradation.

Controlled low-strength material using fly ash and AMD sludge.

Controlled low-strength material (CLSM) is a cementitious material with properties similar to stabilized soil. After hardening, CLSM provides adequate strength in bearing capacity and support but can also be easily excavated. To be classified as a CLSM, the material must have a compressive strength between 450 kPa (65 psi) and 8400 kPa (1200 psi). Typical CLSM contains coal-combustion fly ash (FA), cement, water and fine or coarse aggregate. In this paper, physical and strength properties of CLSM formed by combining sludge, a by-product from the treatment of acid mine drainage (AMD), with Class F FA are investigated. The sludge is a lime-based waste product that when combined with FA, exhibits self-hardening characteristics similar to cement. A main focus of this research is to develop a CLSM mix in which by-product material utilization is maximized while satisfying workability and performance requirements. A mixture of 10% AMD sludge, 2.5% Portland cement (PC), 87.5% Class F FA (dry wt.%) with water provided unconfined compressive strength values within the range for classification as CLSM. This mixture satisfies the excavatability and walkability requirements as well as the hardening time and stability criteria.

Organ transplantation in developing countries.

Organ transplantation has become an effective means of restoring health and saving lives, but a number of difficulties remain to be overcome. Especially in developing countries, greater clarity is needed on the sociocultural, economic, ethical, legal and technical factors involved.

Serotyping of group A rotaviruses in Egyptian neonates and infants less than 1 year old with acute diarrhea.

Group A human rotavirus G serotypes were detected in stool specimens from neonates and infants with and without acute diarrhea in Cairo by using monoclonal antibodies in an enzyme-linked immunosorbent assay. Serotypes G1 and G4 predominated in all age groups. Mixed (G1 plus G4) and nontypeable specimens represented 16.1 and 38.7% of the total number serotyped, respectively.

PIP: Group A human rotavirus (HRV) is the most common cause of acute gastroenteritis among infants worldwide. 7 G serotypes of group A HRV have thus far been identified by neutralization tests, of which 4, serotypes G1 through G4, have a global distribution. Enzyme immunoassay (EIA) was used to detect the relative frequency and temporal distribution of HRV G serotypes 1-4 among the community of neonates and infants with and without acute diarrhea who attended Cairo University Children's Hospital between August 1992 and October 1993. Fecal samples were collected from 20 neonates and 109 infants under age 1 year with acute diarrhea and from 20 neonates and 30 infants without acute diarrhea. Samples were then tested for the presence of rotavirus antigen using a commercial EIA. Rotavirus was identified in 64 of the 180 neonates and infants; in 15 neonates with diarrhea, 6 neonates without diarrhea, and 43 infants aged 1-12 months. Infection peaked between August and December. Serotypes G1 and G4 predominated in all age groups. Mixed (G1 and G4) and nontypeable specimens represented 16.1% and 38.7% of the total number serotyped, respectively.

Health professions development.

Health professions development is an integral part of national health plans. It is influenced by various factors and should be continuously updated to meet the changing health situation and related disciplines of the country. There are three forms of establishing a health manpower development plan: a market-oriented form, a goal-achievement form and a normative form. A combination of all forms is best if carried out by a community-oriented team of academic health professions and health care providers. Although countries of the Eastern Mediterranean Region share many demographic, geographic, and sociocultural characteristics, there are marked differences in resources, health manpower structure and availability in health services. Health professional development plans should be formulated according to existing situations. Other factors influencing health manpower development in the future include political, social and economic trends, changes in morality and disease patterns, industrialization, availability of health services and academic institutions. Perspectives guiding planning for the development of various categories of health professionals are presented.

Nebulizer therapy with antibiotics in chronic suppurative lung disease.

Aerosolized antibiotics have been shown to be a useful modality of treatment in patients with cystic fibrosis. In this investigation we examined the utility of this treatment in patients with other chronic suppurative lung disorders. These included forty patients, thirty men and ten women with chronic airway infection (27 with bronchiectasis, 6 with chronic abscess and 7 with chronic suppurative bronchitis). Pathogenic organisms were isolated from the affected part of the lung by a fiberoptic bronchoscopy using a sterile disposable bronchial microbiology brush. Cultures from these specimens were used to determine the appropriate antibiotic. A second control group of 20 patients was treated with systemic antibiotics alone. Both systemic and aerosolized antibiotics were administered in 20 patients. A statistically significant improvement in clinical, and ventilatory functions was recorded in the first group compared to the second. Nebulized antibiotics used as adjunctive therapy in association with systemic antibiotics may offer a therapeutic advantage in chronic suppurative lung diseases.

Speech manifestations in lateralization of temporal lobe seizures.

To evaluate the role of speech manifestations in lateralization of temporal lobe seizures, we reviewed videotapes of 100 complex partial seizures in 35 patients who underwent temporal lobectomy for intractable epilepsy. All patients had prolonged electroencephalographic video monitoring with scalp and subdural electrodes, and their speech dominance was determined with an intracarotid amobarbital test. Speech manifestations were observed in 79 seizures and were classified as vocalization, normal speech, or abnormal speech. Vocalization of sounds without speech quality occurred ictally in 48.5% of patients. Normal speech (identifiable speech) occurred ictally in 34.2% of patients. Abnormal speech (speech arrest, dysphasia, dysarthria, and nonidentifiable speech) occurred in 51.4% of patients, either ictally or postictally. Of all the above speech manifestations, only postictal dysphasia and ictal identifiable speech had significant lateralizing value: 92% of patients with postictal dysphasia had their seizures originating from the dominant temporal lobe (p less than 0.001), and 83% of those with ictal identifiable speech had their seizures from the nondominant side (p = 0.013). This study shows that speech manifestations are common in complex partial seizures of temporal lobe origin and can provide an excellent clinical tool for lateralization of seizure onset.

Undernutrition and quality of life.

PIP: Malnutrition, the most pervasive human problem especially in less developed countries (LDCs), not only adversely affects quality of life but also socioeconomic development. 25% of pregnant women in LDCs suffer from protein energy malnutrition while only 4% do in developed countries. This and other forms of malnutrition cause low birth weight infants and consequently high infant mortality and morbidity rates and limited fetal brain development. Child mortality due to measles is 200-400 times greater in malnourished children in LDCs than those in developed countries. In addition, measles brings about acute malnutrition in marginally nourished children. Malnutrition also adversely affects fertility, such as reducing a woman's fecundity during the menstrual cycle. Studies demonstrate that severe malnutrition during the 1st 6 months of life and maybe up to the 1st 2 years impairs intellectual development and the effects cannot be reversed. However, breast milk provides adequate nutrition and protects infants from infection when they are most susceptible. Inadequately nourished children are often apathetic, nonresponsive, impulsive; exhibit nongoal directed behavior; do not respond normally in social interactions; and cannot cope with stress or frequent daily demands. Studies indicate that even inadequately nourished adults develop behavior patterns similar to those of malnourished children. A starvation period among adults reduces muscle strength by almost 30% and precision of movements by 15-20%. In addition, childhood malnutrition reduces adult body weight and therefore restricting working capacity. The known effects of malnutrition should convince policy makers of the need to invest in programs that improve the nutritional standards of the populace for humanitarian reasons and to stimulate economic growth.^ieng